PMID- 11757559 TI - [Diet, hygiene, and biology at European primary schools 1770-1945]. PMID- 11757560 TI - [Euthansia in the Netherlands]. PMID- 11757561 TI - [The curing professions: physicians and nurses in history]. PMID- 11757562 TI - [Science illustration as method and art]. PMID- 11757563 TI - Veterans Benefits Administration nomenclature changes. Final rule. AB - This document makes nomenclature changes in VA regulations in 38 CFR Chapter I to reflect current Veterans Benefits Administration titles and office designations. References to the "Chief Benefits Director" are changed to "Under Secretary for Benefits." Also, references to "Vocational Rehabilitation and Counseling" and its abbreviation "VR&C" are changed to "Vocational Rehabilitation and Employment" and "VR&E," respectively. In addition, references to the "Vocational Rehabilitation and Education Service" are changed to "Vocational Rehabilitation and Employment Service" or "Education Service" as appropriate. PMID- 11757564 TI - Federal old-age, survivors and disability insurance; determining disability and blindness; revision to medical-vocational guidelines. Final rules. AB - We are clarifying section 201.00(h) of the medical-vocational guidelines in appendix 2 of sub part P of regulations part 404. This section provides guidance for evaluating disability in individuals under age 50 who have a severe impairment(s) that does not meet or equal in severity the criteria of any listed impairment in appendix 1 of sub part P, but who have a residual functional capacity for no more than the full range of sedentary work and cannot do any past relevant work. The revisions only clarify the current rules. PMID- 11757565 TI - Legal assistance matters. Final rule. AB - This part establishes a uniform approach for the execution of military testamentary instruments (including wills), powers of attorney, and advance medical directives. It seeks public comment on specific aspects of the activity. PMID- 11757566 TI - TRICARE; Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); payments for professional services in low-access locations. Final rule. AB - This final rule implements 10 U.S.C. 1097 b(a), as added by section 716 of the National Defense Authorization Act for Fiscal Year 2000 which allows higher provider reimbursement rates than normally allowable, with certain limitations, when necessary to ensure an adequate TRICARE Prime network of qualified providers. This final rule also implements 10 U.S.c. 1079(h)(5), as added by section 747 of the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001, to remedy circumstances in which TRICARE beneficiaries face very severe limitations on access to needed health care services. PMID- 11757567 TI - Medicare program; replacement of reasonable charge methodology by fee schedules for parenteral and enteral nutrients, equipment, and supplies. Final rule. AB - This final rule implements fee schedules for payment of parenteral and enteral nutrition (PEN) items and services furnished under the prosthetic device benefit, defined in section 1861(s)(8) of the Social Security Act. The authority for establishing these fee schedules is provided by the Balanced Budget Act of 1997, which amended the Social Security Act at section 1842(s). Section 1842(s) of the Social Security Act specifies that statewide or other area wide fee schedules may be implemented for the following items and services still subject to the reasonable charge payment methodology: medical supplies; home dialysis supplies and equipment; therapeutic shoes; parenteral and enteral nutrients, equipment, and supplies; electromyogram devices; salivation devices; blood products; and transfusion medicine. This final rule describes changes made to the proposed fee schedule payment methodology for these items and services and provides that the fee schedules for PEN items and services are effective for all covered items and services furnished on or after January 1, 2002. Fee schedules will not be implemented for electromyogram devices and salivation devices at this time since these items are not covered by Medicare. In addition, fee schedules will not be implemented for medical supplies, home dialysis supplies and equipment, therapeutic shoes, blood products, and transfusion medicine at this time since the data required to establish these fee schedules are inadequate. PMID- 11757568 TI - Novel optical methodologies in studying mechanical signal transduction in mammalian cells. AB - For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research. PMID- 11757569 TI - A comparative analysis of the center of gravity and center of pressure trajectory path lengths in standing posture: an estimation of active stiffness. AB - The center of foot pressure (CP) motions, representing the net neuromuscular control, was compared to the center of gravity (CG) motions, representing the net performance. The comparison focused on the trajectory path length parameter along the medio-lateral and antero-posterior axes because these two variables depend on amplitude versus frequency relationship. This relationship was used to evaluate the CG motions based on the CP motions. Seven subjects stood still on a force plate with eyes open and eyes closed. The results showed that the ratio of (CP CG)/CP trajectory path length was personal for each subject. These results suggest different levels of passive (ligaments, elastic properties) and active (reflex activity) stiffness. For some subjects, this ratio was significantly lower for the eyes open condition than for the eyes closed condition, indicating a decrease of the active stiffness for the eyes open condition. Therefore, a CG CP comparative analysis appeared helpful in understanding the control of balance and necessary to quantify the subjects' net performance. PMID- 11757570 TI - Mid-infrared trace gas detection using continuous-wave difference frequency generation in periodically poled RbTiOAsO4. AB - A tunable mid-infrared continuous-wave (cw) spectroscopic source in the 3.4-4.5 micrometers region is reported, based on difference frequency generation (DFG) in a quasi-phase-matched periodically poled RbTiOAsO4 (PPRTA) crystal. DFG power levels of 10 microW were generated at approximately 4 micrometers in a 20-mm long PPRTA crystal by mixing two cw single-frequency Ti:Al2O3 lasers operating near 713 nm and 871 nm, respectively, using a laser pump power of 300 mW. A quasi phase-matched infrared wavelength-tuning bandwidth (FWHM) of ~ 12 cm-1 and a temperature tuning rate of 1.02 cm-1/degree C were achieved. Experimental details regarding the feasibility of trace gas detection based on absorption spectroscopy of CO2 in ambient air using this DFG radiation source are also described. PMID- 11757571 TI - Duty to assist. Final rule. AB - This document amends the Department of Veterans Affairs (VA) adjudication regulations to implement the provisions of the Veterans Claims Assistance Act of 2000 (the VCAA), which was effective on November 9,2000. The intended effect of this regulation is to establish clear guidelines consistent with the intent of Congress regarding the timing and the scope of assistance VA will provide to a claimant who files a substantially complete application for VA benefits or who attempts to reopen a previously denied claim. PMID- 11757572 TI - Requirements for facilities transferring or receiving select agents. Final rule. AB - CDC administers regulations that govern the transfer of certain biological agents and toxins ("select agents"). These regulations require entities that transfer or receive select agents to register with CDC and comply with biosafety standards contained in the Third Edition of the CDC/NIH publication "Biosafety in Microbiological and Biomedical Laboratories ("BMBL")." On October 28,1999, CDC published a Notice of Proposed Rulemaking ("NPRM") seeking both to revise the biosafety standards facilities must follow when handling select agents and to provide new biosecurity standards for such facilities. These new standards are contained in the Fourth Edition of BMBL, which the NPRM proposed to incorporate by reference, thereby replacing the Third Edition. No comments were received in response to this proposal. CDC is therefore amending its regulations to incorporate the Fourth Edition. PMID- 11757573 TI - Biodegradable polymers. PMID- 11757574 TI - Medicaid program; modification of the Medicaid upper payment limit transition period for inpatient hospital services, outpatient hospital services, nursing facility services, intermediate care facility services for the mentally retarded, and clinic services. Final rule. AB - This final rule modifies the Medicaid upper payment (UPL) limit provisions by establishing a new transition period for States that submitted plan amendments before March 13, 2001 that do not comply with the new UPLs effective on that date (but do comply with the prior UPLs) and were approved on or after January 22, 2001. This new transition period applies to payments for inpatient hospital services, outpatient hospital services, nursing facility services, intermediate care facility services for the mentally retarded, and clinic services. PMID- 11757575 TI - Rotating reverse osmosis: a dynamic model for flux and rejection. AB - Reverse osmosis (RO) is a compact process for the removal of ionic and organic pollutants from contaminated water. However, flux decline and rejection deterioration due to concentration polarization and membrane fouling hinders the application of RO technology. In this study, a rotating cylindrical RO membrane is theoretically investigated as a novel method to reduce polarization and fouling. A dynamic model based on RO membrane transport incorporating concentration polarization is used to predict the performance of rotating RO system. Operating parameters such as rotational speed and transmembrane pressure play an important role in determining the flux and rejection in rotating RO. For a given geometry, a rotational speed sufficient to generate Taylor vortices in the annulus is essential to maintain high flux as well as high rejection. The flux and rejection were calculated for wide range of operating pressures and rotational speeds. PMID- 11757576 TI - Medicare program; payments for new medical services and new technologies under the acute care hospital inpatient prospective payment system. Final rule. AB - This final rule establishes a mechanism for increased Medicare payments for new medical services and technologies furnished to Medicare beneficiaries under the acute care hospital inpatient prospective payment system. The rule implements section 533 of the Medicare, Medicaid, and SCHIP [State Children's Health Insurance Program] Benefits Improvement and Protection Act of 2000; and finalizes related regulatory provisions that were addressed in a proposed rule published in the Federal Register on May 4, 2001 (66 FR 22646). PMID- 11757577 TI - Medicare program; requirements for recredentialing of Medicare+Choice organization providers. Final rule. AB - This final rule changes the requirement for recredentialing providers who are physicians or other health care professionals for Medicare+Choice Organizations(M+COs) from at least every 2 years to at least every 3 years. This change is consistent with managed care industry recognized standards of practice and quality, and with standards already adopted by nationally recognized private quality assurance accrediting organizations. This change simplifies administrative requirements by retaining consistency with the private accrediting processes. This rule benefits M+COs and providers within theM+COs who must be recredentialed, while continuing to address quality issues of Medicare beneficiaries. PMID- 11757578 TI - The Martian and extraterrestrial UV radiation environment. Part II: further considerations on materials and design criteria for artificial ecosystems. AB - Ultraviolet radiation is an important natural physical influence on organism function and ecosystem interactions. The UV radiation fluxes in extraterrestrial environments are substantially different from those experienced on Earth. On Mars, the moon and in Earth orbit they are more biologically detrimental than on Earth. Based on previously presented fluxes and biologically weighted irradiances, this paper considers in more detail measures to mitigate UV radiation damage and methods to modify extraterrestrial UV radiation environments in artificial ecosystems that use natural sunlight. The transmission characteristics of a Martian material that will mimic the terrestrial UV radiation environment are presented. Transmissivity characteristics of other Martian and lunar materials are described. Manufacturing processes for the production of plastics and glass on the lunar and Martian surface are presented with special emphasis on photobiological requirements. Novel UV absorbing configurations are suggested. PMID- 11757579 TI - Mutation analysis in Turkish patients with hereditary fructose intolerance. AB - Thirteen Turkish patients with hereditary fructose intolerance (HFI) were screened for the three common mutations, A149P, A174D and N334K, in the aldolase B gene that have been detected frequently in European population. We found that nine of the patients carry the A149P mutation in both alleles, which corresponds to a frequency of about 55%. Single-strand conformation analysis of all coding exons of the gene was also performed to detect unknown mutations in four patients not carrying the three common mutations. No aberrant migration patterns were observed in these patients. PMID- 11757580 TI - Very low-density lipoprotein apolipoprotein B-100 turnover in glycogen storage disease type Ia (von Gierke disease). AB - Mixed hyperlipidaemia is a common finding in glycogen storage disease type Ia (GSD Ia). Although cross-sectional studies have demonstrated increases in intermediate-density lipoproteins (IDLs) and reductions in lipoprotein lipase activity, no studies have investigated the dynamics of apolipoprotein B-100 (apo B) metabolism in GSD Ia. This study investigated apoB turnover in GSD Ia using an exogenous labelling method in one sib from a kinship with established GSD Ia. The study demonstrated normal hepatic secretion of very low-density lipoprotein (VLDL), but hypocatabolism of VLDL, probably due to lack of lipoprotein lipase activity. The production rate of IDL was slightly increased, but the turnover rate of low-density lipoprotein was normal. The findings suggest that, as well as a corn starch diet and dietary fat restriction, treatment of severe mixed hyperlipidaemia in GSD Ia and its attendant risk of pancreatitis should possibly involve fibrates that activate lipoprotein lipase and may enhance the clearance of IDL, rather than omega-3 fatty acids, which principally suppress hepatic secretion of VLDL. PMID- 11757581 TI - Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId. AB - We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (117-1120) and a 98 bp deletion (1135-1232) in cDNA. Sequencing of the genomic DNA of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic DNA. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice-site sequence. If normal splicing had occurred, a stop codon would have appeared within exon II due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice-site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient. PMID- 11757582 TI - Decreased half-life of insulin-like growth factor I in Rabson-Mendenhall syndrome. AB - Rabson-Mendenhall syndrome is an autosomal recessive disorder of insulin signalling caused by mutations in the insulin receptor gene. Affected patients are insensitive to exogenous insulin. Insulin-like growth factor I (IGF-I), whose receptor is similar to the one for insulin and is not impaired in this condition, is not always effective in these patients. To understand the reason for this failure, IGF-I concentrations were measured in a patient after subcutaneous injection of 0.1 and 0.2 mg/kg of rhIGF-I. IGF-I concentrations increased only transiently because of the short half-life (1.3-3 h, compared to a normal range of 17-22 h). No correlation was found between IGF-I concentrations and glucose or insulin concentrations. The short half-life of IGF-I may contribute to treatment failure in patients with inherited insulin-resistant syndromes. PMID- 11757583 TI - A case of PDH-E1 alpha mosaicism in a male patient with severe metabolic lactic acidosis. AB - We have characterized a novel mutation in a male patient that affects the coding sequence of PDH-E1 alpha gene and changes arginine-141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fibroblasts, liver and muscle), a scenario that would indicate a case of E1 alpha mosaicism in a male patient. When the mutant E1 alpha protein was expressed in human skin fibroblasts with zero endogenous pyruvate dehydrogenase complex activity and E1 alpha protein expression, no significant restoration of activity was recorded, in contrast to the wild-type cDNA. even though both wild-type and mutant protein levels were comparable. We concluded that the R141L mutation is a severe one and that it must have occurred in one of the E1 alpha alleles during early embryogenesis. PMID- 11757584 TI - Phenotype variability in 130 adult patients with respiratory chain disorders. AB - Despite continuously improving diagnostic facilities, respiratory chain disorders (RCDs) are easily overlooked or misdiagnosed. We thus studied phenotype variability and the diagnostic potential of clinical and laboratory investigations in patients with RCD. We retrospectively evaluated clinical and laboratory investigations in 130 patients with RCD: 63 women and 67 men, aged 17 87 years, diagnosed between January 1992 and December 1999. mtDNA mutations were found in 20 patients; a respiratory chain defect but no mutation in 4; an abnormal lactate stress test but no mutation or biochemical defect in 66; and ragged-red fibres or reduced oxidative enzyme staining but no mutation, biochemical defect or abnormal lactate stress test in 40 patients. The most frequent initial manifestation of RCD were limb weakness, muscle pain and sensory disturbances. The most frequent clinical findings at diagnosis were muscle pain, fatiguability, limb weakness, reduced tendon reflexes and muscle wasting, irrespective of the diagnostic evidence. Mean age at onset, disease duration and time until diagnosis were 39, 14 and 13 years, respectively, without sex differences. The family history was positive in 29% of the patients. Hyperlipidaemia was found in 45%, hyper-CK-aemia in 42%, short stature in 33%, thyroid dysfunction in 17%, diabetes in 12%, and epilepsy in 8% of the patients. Laboratory investigations that prove useful to support the diagnosis of RCD are muscle biopsy, electromyography, lactate stress testing, echocardiography and mtDNA analysis. Systems most often involved in RCDs were the PNS, CNS, endocrine system and heart. The diagnosis of RCD requires awareness of the great phenotypic heterogeneity and an individualized, integral, multidisciplinary approach. PMID- 11757585 TI - Delayed lysosomal metabolism of lipids in mucolipidosis type IV fibroblasts after LDL-receptor-mediated endocytosis. AB - We specifically probed the low-density lipoprotein-receptor-dependent endosomal/lysosomal pathway of lipid degradation in control and mucolipidosis type IV fibroblasts using either [choline-methyl-14C]sphingomyelin in complex with apolipoprotein E, or cholesteryl [14C]oleate-labelled low-density lipoprotein as a substrate. Mucolipidosis type IV fibroblasts metabolized [14C]sphingomyelin and cholesteryl [14C]oleate significantly more slowly than controls and fibroblasts from patients with Hurler disease or Niemann-Pick disease type C. So far, no lysosomal enzyme deficiency has been reported for mucolipidosis type IV. Rather, the defect in mucolipidosis type IV cells has recently been suggested to be related to intracellular trafficking. Our results suggest that the defect in mucolipidosis type IV also affects the low-density lipoprotein-receptor-mediated endocytosis pathway. PMID- 11757586 TI - Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency. AB - Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy. PMID- 11757587 TI - Propionic acidaemia with basal ganglia stroke: treatment of acute extrapyramidal symptoms with L-DOPA. AB - A 15-year-old male with propionic acidaemia developed neurological complications secondary to basal ganglia involvement. Treatment with L-DOPA had a positive effect on his extrapyramidal syndrome. PMID- 11757588 TI - Successful pregnancy outcome in atypical hyperglycinaemia. AB - A female patient with atypical nonketotic hyperglycinaemia is reported having undergone two successful pregnancies. During pregnancy, plasma glycine was raised. Neuropsychometric outcome of both offspring shows IQs average for population. PMID- 11757589 TI - Lethal neonatal presentation of carnitine palmitoyltransferase I deficiency. AB - A neonate subsequently diagnosed with carnitine palmitoyltransferase I deficiency died at 34 h of untreatable bradycardia. There was fatty infiltration of the liver and increased free carnitine and reduced acylcarnitines in the blood. PMID- 11757590 TI - Mucolipidosis II (I-cell disease) presenting as neonatal cholestasis. PMID- 11757591 TI - Neuroleptic malignant syndrome during zuclopenthixol therapy in X-linked cerebral adrenoleukodystrophy. AB - An 8 year-old boy with X-ALD under treatment with simvastatin developed a severe adverse reaction when the dose of his other medication, zuclopenthixol was increased. Both drugs were withdrawn after a diagnosis of neuroleptic malignant syndrome was made. PMID- 11757592 TI - Increased fertility in a woman with classic galactosaemia. AB - A 27-year-old caucasian female with classical galactosaemia due to Q188R homozygous mutation is reported. At 18 years she had triplets and at 23 years a further pregnancy. All infants are well. PMID- 11757593 TI - Accounting for spatial variation of ozone productivity in NOx emission trading. AB - The potential air quality benefits of NO(x) emission-trading programs were compared to the air quality benefits of across-the-board NO(x) reductions for point sources in eastern Texas. The comparison was performed by first determining, using the Comprehensive Air Quality Model with extensions (CAMx), the changes in ozone concentrations associated with NO(x) reductions at more than 50 individual facilities in eastern Texas. These facility-specific changes in ozone concentrations due to NO(x) reductions were then converted into a variety of indices representing ozone reduction benefits. Trading scenarios were then evaluated through Monte Carlo simulations. The results indicate that approximately 20% of all trading scenarios result in ozone reduction benefits that deviate by 25% or more from the ozone reduction benefits achieved by across the-board reductions. This result was independent of the index used to calculate ozone reduction benefit. This variability in the benefits associated with trading scenarios was comparable to the variability in benefits associated with changes in meteorological conditions over the days that were modeled. Additional Monte Carlo simulations indicated that the average benefit associated with NO(x) trading could be improved and that the variability in benefit was reduced by creating a trading program where a small group of high impact facilities are allowed to sell but may not buy NO(x) allowances. PMID- 11757594 TI - Methodologies for estimating emissions for the U.S. EPA's NOx SIP call, CER rule, and other complexities. AB - Emissions inventories play an important role in many air quality decisions, and the importance of obtaining correct emissions data challenges the emissions inventory community to continuously improve its estimation techniques. The Clean Air Act Amendments of 1990 requires states with ozone nonattainment areas (NAAs) to submit periodically a comprehensive, accurate, and actual inventory of ozone precursor emissions until the areas are redesignated to attainment. They require the states with NAAs to report peak ozone season daily and annual estimates of the inventories for the counties that are in nonattainment. The recently proposed U.S. Environmental Protection Agency's (EPA) NO(x) SIP call and the Consolidating Emissions Reporting (CER) rule are more demanding still. The CER rule requires the states to report statewide point source inventories, 3-yr cycle inventories, and NO(x) SIP call inventories by county for all source types, regardless of the attainment status; the estimating periods are peak ozone season daily, 5-month ozone season, and annual estimates. Furthermore, complexities in emissions inventories such as estimating the emissions with different seasonal and multiple controls exist. These complexities and methodologies for estimating emissions for different time periods are not addressed sufficiently either by the EPA's procedure manuals or by the Emissions Inventory Improvement Program guidance documents. This paper presents methodologies for estimating emissions for different time periods and multiple controls. These methodologies will help the EPA, state, and local government agencies to meet the evolving demands of emissions inventories and the reporting requirements of the NO(x) SIP call and the CER rules. PMID- 11757595 TI - Addressing uncertainty and conflicting cost estimates in revising the arsenic MCL. AB - The current effort to revise the arsenic drinking water standard is one of the first times that the promulgation of a Maximum Contaminant Level (MCL) for drinking water has been influenced explicitly by benefit-cost considerations. Different stakeholders have developed different estimates of the costs, benefits, and appropriate decision-making criteria for a lower standard. In this study, alternative analyses prepared by the U.S. EPA and by independent researchers are compared. The large discrepancies in the aggregate national cost estimates are shown to result largely from differences in the engineering cost estimates for arsenic treatment processes. Further research is needed to resolve these discrepancies. Alternative regulatory approaches, such as providing point-of-use treatment or exempting water systems with high household compliance costs, yield only modest improvement in the overall cost-effectiveness of lower standards but are effective at addressing serious affordability problems for the small percentage of (primarily small) water systems where these problems are predicted to occur. The U.S. EPA may wish to provide more explicit guidance to state regulators and to water utilities as to the conditions under which these options will be acceptable. PMID- 11757596 TI - Separation of structural components in soil organic matter by diffusion ordered spectroscopy. AB - Diffusion ordered spectroscopy (DOSY) was applied to two extracts of organic matter from the surface horizon of an oak forest soil. It was possible to identify and confirm the presence of numerous aliphatic, aromatic, sugar, and amino acid components that could be separated on the basis of diffusion in DMSO d6 and D2O. On average, sugar components were identified as the largest molecules in solution, with molecular masses up to approximately 1500 Da followed by the aliphatic and aromatic components. Amino acids with a range of molecular weights were also identified in the mixture. The summation of the individual slices from the DOSY experiment closely resembles the conventional 1H spectra of the material, indicating that the components identified with DOSY represent all the components present in the mixture. The separation of components in the mixture in organic solvent supports new findings that fulvic and humic acids are not cross linked, high molecular weight macromolecules but are instead aggregates composed of relatively simple molecules that take on colloidal properties in the presence of metal ions in aqueous solution. Using the knowledge that these organic mixtures are combinations of relatively simple entities with well-documented reactivities and behavior will improve our ability to predict and model their interactions and fate under natural conditions. PMID- 11757597 TI - Passive ozone network of Dallas: a modeling opportunity with community involvement. 2. AB - Attaining the current lower tropospheric U.S. ozone standards continues to be a difficult task for many areas in the U.S. Concentrations of ozone above the standards negatively affects human health, agricultural crops, forests, and other ecosystem elements. This paper describes year two (1999) of a regional networking of passive and continuous ozone monitoring sites in the Dallas-Fort Worth (DFW) Metroplex region. The objectives of the second year of study were to (1) validate conclusions of the 1998 Passive Ozone Network of Dallas (POND) I study, (2) define the value of taking 12-h diurnal samples in addition to 24-h samples, and (3) add to the scientific knowledge base of rural/urban ozone comparison studies. Results of the POND II (1999) study demonstrated that ozone concentrations exceeding the new 8-h ozone standard could be recorded at least 130 km, or 80 miles, from the DFW Metroplex core in more rural areas. In addition, results of the POND II study indicated that ozone concentrations exceeding the 8-h standard probably occurred in areas recording a 12-h daytime ozone concentration above 60 parts per billion (ppb). The 12-h passive ozone data from POND II also suggests the relative magnitude of anthropogenic pollution influence could be assessed for rural passive ozone sites. The data from the POND II study provide modelers a rich database for future photochemical subgrid development for the DFW ozone nonattainment area. Indeed, the POND database provides a great amount of additional ozone ambient data covering 26 8-h and 13 1-h ozone standard exceedance days over an approximate 25000 km2 region. These data should help decrease uncertainties derived from future DFW ozone model exercises. PMID- 11757598 TI - Contribution of individual sorbents to the control of heavy metal activity in sandy soil. AB - A multisurface model is used to evaluate the contribution of various sorption surfaces to the control of heavy metal activity in sandy soil samples at pH 3.7 6.1 with different sorbent contents. This multisurface model considers soil as a set of independent sorption surfaces, i.e. organic matter (NICA-Donnan), clay silicate (Donnan), and iron hydroxides (DDL, CD-MUSIC). The activities of Cu2+, Cd2+, Zn2+, Ni2+, and Pb2+ in equilibrium with the soil have been measured using a Donnan membrane technique. The metal activities predicted by the model agree with those measured reasonably well over a wide concentration range for all the metals of interest except for Pb. The modeling results suggest that soil organic matter is the most important sorbent that controls the activity of Cu2+, Cd2+, Zn2+, and Ni2+ in these sandy soils. When metal loading is high in comparison with soil organic matter content, the contribution of clay silicates to metal binding becomes more important. Adsorption to iron hydroxides is found not significant in these samples for Cu, Cd, Zn, and Ni. However, for Pb the model estimates strong adsorption on iron hydroxides. The model predicts that acidification will not only lead to increased solution concentrations but also to a shift toward more nonspecific cation-exchange type binding especially for the metals Cd, Zn, and Ni. Lowering the pH has led to a loss of 56% of Cd, 69% of Zn, and 66% of Ni during 16 years due to increased leaching. PMID- 11757599 TI - Interpreting nonracemic ratios of chiral organochlorines using naturally contaminated fish. AB - Although reports of nonracemic proportions of chiral organochlorine pollutants in the environment are widespread, the interpretation of such data is not well developed. Using GC/MS and a chiral stationary phase consisting of 25% tert butyldimethylsilylated beta-cyclodextrin in PS086 (beta-BSCD), we followed the change in the enantiomeric signature of 2-exo,3-endo,6-exo,8,9,10 hexachlorobornane (B6-923) in naturally contaminated fish maintained under toxaphene-free conditions. Whereas the enantiomeric ratio (ER) of B6-923 was near racemic at the start of the elimination experiment, it had increased severalfold by the end of 60 d. On the basis of first-order kinetics, one enantiomer of B6 923 was eliminated twice as fast as its mirror image, resulting in half-lives of 7 and 13 d, respectively. Enantioselective elimination by our test fish (Fundulus sp.) strongly suggests active biotransformation of B6-923; however, bioprocessing throughput estimates suggest a very low in situ rate of natural attenuation. These results confirm that the relatively constant ERs observed for chiral organochlorines in a given species are the result of competing processes, e.g., uptake vs elimination. Our experiments also further illustrate the utility of enantioselective analysis in characterizing the biotransformation of persistent organochlorine pollutants. PMID- 11757600 TI - Further biogeochemical characterization of a trichloroethene-contaminated fractured dolomite aquifer: electron source and microbial communities involved in reductive dechlorination. AB - A recent article presented geochemical and microbial evidence establishing metabolic adaptation to and in-situ reductive dechlorination of trichloroethene (TCE) in a fractured dolomite aquifer. This study was designed to further explore site conditions and microbial populations and to explain previously reported enhancement of reductive dechlorination by the addition of pulverized dolomite to laboratory microcosms. A survey of groundwater geochemical parameters (chlorinated ethenes, ethene, H2, CH4, DIC, DOC, and delta13C values for CH4, DIC, and DOC) indicated that in situ reductive dechlorination was ongoing and that an unidentified pool of organic carbon was contributing, likely via microbial respiration, to the large and relatively light on-site DIC pool. Petroleum hydrocarbons associated with the dolomite rock were analyzed by GC/MS and featured a characteristically low delta13C value. Straight chain hydrocarbons were extracted from the dolomite previously found to stimulate reductive dechlorination; these were particularly depleted in hexadecane (HD). Thus, we hypothesized that HD and related hydrocarbons might be anaerobically respired and serve both as the source of on-site DIC and support reductive dechlorination of TCE. Microcosms amended with pulverized dolomite demonstrated reductive dechlorination, whereas a combusted dolomite amendment did not. HD-amended microcosms were also inactive. Therefore, the stimulatory factor in the pulverized dolomite was heat labile, but that component was not HD. Amplified Ribosomal DNA Restriction Analysis (ARDRA) of the microbial populations in well waters indicated that a relatively low diversity, sulfur-transforming community outside the plume was shifted toward a high diversity community including Dehalococcoides ethenogenes-type microorganisms inside the zone of contamination. These observations illustrate biogeochemical intricacies of in situ reductive dechlorination reactions. PMID- 11757601 TI - Gaseous transport of volatile organic chemicals in unsaturated porous media: effect of water-partitioning and air-water interfacial adsorption. AB - Laboratory experiments were conducted employing gas chromatographic techniques to evaluate the gaseous transport of volatile organic chemicals (VOCs) in water unsaturated soil columns as influenced by interfacial (air-water) adsorption and water partitioning. VOCs [methylene chloride, tetrachloroethene (PCE), 1,1,1 trichloroethane (TCA), ethyl-benzene, p-xylene, chlorobenzene] with different water-partitioning and interfacial adsorption coefficients (air-water) were used to evaluate the theoretical basis of using these coefficients to predict the retardation factors (Rt) observed during gaseous transport. A loamy sand from Dover Air Force Base, DE, and a commercial sand were used as the column packing material to assess the effect of grain size on the air-water interfacial area (ai) and retardation at different water saturations (Sw). The ai were measured using n-alkanes. At low Sw, interfacial adsorption contributed most to the retardation for all VOCs during gaseous transport in the Dover soil which has little sorption capacity for the VOCs. As Sw increased, the fraction of Rt attributed to interfacial adsorption decreased, while that due to water partitioning increased for all of the VOCs used for this study. For the sand, with a more uniform grain-size distribution than the Dover soil, the contribution of air-water interfacial adsorption to the Rt of a VOC (p-xylene) was not as significant as that for the Dover soil due to small ai. The fractions of Rt attributed to interfacial adsorption and water partitioning were quantified. The observed Rt for the VOCs agreed well with those predicted based on the sorption coefficients and the quantities of sorption domains (Sw, ai). PMID- 11757602 TI - Tracing the origin of pollution in French Alpine snow and aerosols using lead isotopic ratios. AB - Fresh snow samples collected at 15 remote locations and aerosols collected at one location in the French Alps between November 1998 and April 1999 have been analyzed for Pb concentration and isotopic composition by thermal ionization mass spectrometry. The snow samples contained 19-1300 pg/g of Pb with isotopic ratios 206Pb/207Pb (208Pb/207Pb) of 1.1279-1.1607 (2.3983-2.4302). Airborne Pb concentrations at one sampling site ranged from 0.42 to 6.0 ng/m3 with isotopic ratios of 1.1321-1.1427 (2.4029-2.4160). Air mass trajectory analysis combined with isotopic compositions of potential source regions did not show discernible evidence of the long-range atmospheric transport of pollutants. Isotopic ratios in the Alpine snow samples and thus the free troposphere were generally higher than airborne Pb isotopic ratios in urban France, which coupled with the relatively high Pb concentrations suggested a regional anthropogenic Pb source, probably Italy but possibly Eastern Europe. PMID- 11757603 TI - 129I and 127I transport in the Mississippi River. AB - The watershed processes which control 129I/127I ratios, 129I and 127I concentrations, and speciation of iodine isotopes were studied through an investigation into the variability of these parameters in the Mississippi River near New Orleans, undertaken in 1996-1998. Analyses of suspended particulate matter (SPM) revealed a greater percent association of 127I than of 129I, resulting in lower 129I/127I ratios in SPM than in surrounding water. Furthermore, crossflow ultrafiltration showed that organo-iodine was the dominant form for both isotopes, with 70-85% of these isotopes found in the 0.45 microm filter-passing fraction associated with colloidal macromolecular organic matter. 129I showed a weak correlation, 127I no correlation, and 129I/127I ratios a strong inverse correlation with river flow rate. Inverse correlations between 129I/127I ratios and river flow rates can be best explained by rainwater and evapotranspiration dominated ratios at base flow and a lowering of the isotope ratios during higher flow due to extra inputs of 127I from soil weathering. We postulate that different equilibration times for 127I and 129I as well as for bomb-produced 129I and reprocessing-produced 129I are responsible for these fractionation effects and the differential mobilities of these isotopes in the Mississippi River watershed. PMID- 11757604 TI - Products of the OH radical-initiated reaction of 3-hexene-2,5-dione. AB - 3-Hexene-2,5-dione [CH3C(O)CH=CHC(O)CH3] and other unsaturated 1,4-dicarbonyls are formed from the atmospheric photooxidations of aromatic hydrocarbons. We have investigated the products of the gas-phase reaction of OH radicals with 3-hexene 2,5-dione in the presence of NO at room temperature and atmospheric pressure of air using in situ atmospheric pressure ionization tandem mass spectrometry. Products of molecular weight 102 and 191 were identified and from consideration of the potential reactions these are attributed to CH3C(O)CH(OH)CHO and CH3C(O)CH(OH)CH(ONO2)C(O)CH3, respectively. After initial addition of the OH radical, the CH3C(O)CH(OH)(*C)HC(O)CH3 radical adds O2 to form the peroxy radical which reacts with NO to yield the molecular weight 191 hydroxynitrate CH3C(O)CH(OH)CH(ONO2)C(O)CH3 or the hydroxyalkoxy radical CH3C(O)CH(OH)CH(*O)C(O)CH3 plus NO2. Our observation of a molecular weight 102 species indicates that the CH3C(O)CH(OH)CH(*O)C(O)CH3 radical dominantly decomposes to CH3C(O)CH(OH)CHO plus CH3(*C)O, rather than decomposing to CH3C(O)CHO plus CH3C(O)(*C)HOH, isomerizing, or reacting with O2. Thermochemical calculations and an empirical estimation method for calculating alkoxy radical reaction rates are consistent with our experimental observations. PMID- 11757605 TI - Nitrate-cancrinite precipitation on quartz sand in simulated Hanford tank solutions. AB - Caustic NaNO3 solutions containing dissolved Al were reacted with quartz sand at 89 degrees C to simulate possible reactions between leaked nuclear waste and primary subsurface minerals at the U.S. Department of Energy's Hanford site in Washington. Nitrate-cancrinite began to precipitate onto the quartz after 2-10 days, cementing the grains together. Estimates of the equilibrium constant for the precipitation reaction differ for solutions with 0.1 or 1.0 m OH- (log Keq = 30.4 +/- 0.8 and 36.2 +/- 0.6, respectively). The difference in solubility may be attributable to more perfect crystallinity (i.e., fewer stacking faults) in the higher-pH cancrinite structure. This is supported by electron micrographs of crystal morphology and measured rates of Na volatilization under an electron beam. Precipitate crystallinity may affect radionuclide mobility, because stacking faults in the cancrinite structure can diminish its zeolitic cation exchange properties. The precipitation rate near the onset of nucleation depends on the total Al and Si concentrations in solution. The evolution of experimental Si concentrations was modeled by considering the dependence of quartz dissolution rate on AI(OH)4- activity, cancrinite precipitation, and the reduction of reactive surface area of quartz due to coverage by cancrinite. PMID- 11757606 TI - Single-particle analysis of aerosols at Cheju Island, Korea, using low-Z electron probe X-ray microanalysis: a direct proof of nitrate formation from sea salts. AB - A recently developed electron probe X-ray microanalysis (EPMA), called low-Z EPMA, employing an ultrathin window energy-dispersive X-ray detector, was applied to characterize aerosol particles collected at two sampling sites, namely, Kosan and 1100 Hill of Cheju Island, Korea, on a summer day in 1999. Since low-Z EPMA can provide quantitative information on the chemical composition of aerosol particles, the collected aerosol particles were classified and analyzed based on their chemical species. Many different particle types were identified, such as marine-originated, carbonaceous, soil-derived, and anthropogenic particles. Marine-originated particles, such as NaNO3- and Na2SO4-containing particles, are very frequently encountered in the two samples. In this study, it was directly proven that the observed nitrate particles were from sea salts. In addition, two types of nitrate particles from sea salts were observed, with and without Mg. The sodium nitrate particles without Mg were believed to be collected as crystalline form, either with the sodium nitrate particles being fractionally recrystallized within evaporating seawater drops or with recrystallized sodium chloride particles having reacted with gaseous nitrogen species in the air to form the crystalline sodium nitrate particles. The other seemed to be collected as seawater drops, where the atmospheric reaction had occurred in the droplets, and thus sodium as well as magnesium nitrates were observed. Carbonaceous particles are the most abundant in the samples at both sites. From this study, it was found that about three-quarters of the carbonaceous particles in the samples were biogenic, which partially explains a previously reported observation of a large concentration of organic carbon particles as compared to elemental carbon. Various soil-derived particles were also observed. In addition to aluminosilicate and iron oxide-containing particles, which are ubiquitous components in soil derived particles, CaCO3-, Al2O3- and Cr-containing particles were also frequently encountered. PMID- 11757607 TI - The hygroscopic properties of dicarboxylic and multifunctional acids: measurements and UNIFAC predictions. AB - The role of water-soluble organic compounds on the hygroscopic properties of atmospheric aerosols has recently been the subject of many studies. In particular, low molecular weight dicarboxylic acids and some multifunctional organic acids have been found or are expected to exist in atmospheric aerosols in urban, semiurban, rural, and remote sites. Unlike for their inorganic counterparts, the hygroscopic properties of organic acids have not been well characterized. In this study, the hygroscopic properties of selected water soluble dicarboxylic acids (oxalic acid, malonic acid, succinic acid, and glutaric acid) and multifunctional acids (citric acid, DL-malic acid, and L-(+) tartaric acid) were studied using single droplets levitated in an electrodynamic balance at 25 degrees C. The water activities of bulk samples of dilute solutions were also measured. Solute evaporation was observed in the dicarboxylic acids but not in the multifunctional acids. Oxalic acid, succinic acid, and glutaric acid droplets crystallize upon evaporation of water, but, except for glutaric acid droplets, do not deliquesce even at 90% relative humidity (RH). Mass transfer limitation of the deliquescence process was observed in glutaric acid. Neither crystallization nor deliquescence was observed in malonic acid, citric acid, DL malic acid, or L-(+)-tartaric acid. Malonic acid and these three hydroxy carboxylic acids absorb water even at RH much lower than their respective deliquescence RH. The growth factor (Gf), defined as the ratio of the particle diameter at RH = 10% to that at RH = 90%, of oxalic acid and succinic acid was close to unity, indicating no hygroscopicity in this range. The remaining acids (malonic acid, glutaric acid, citric acid, malic acid, and tartaric acid) showed roughly similar hygroscopicity of a Gf of 1.30-1.53, which is similar to that of "more hygroscopic" aerosols in field measurements reported in the literature. A generalized equation for these four acids, Gf = (1-aw)-0.163, was developed to represent the hygroscopicity of these acids. Water activity predictions from calculations using the UNIFAC model were found to agree with the measured water activity data to within 40% for most of the acids but the deviations were as large as about 100% for malic acid and tartaric acid. We modified the functional group interaction parameters of the COOH(-H20, OH-H20, and OH-COOH pairs by fitting the UNIFAC model with the measured data. The modified UNIFAC model improves the agreement of predictions and measurements to within 38% for all the acids studied. PMID- 11757608 TI - Particle release and permeability reduction in a natural zeolite (clinoptilolite) and sand porous medium. AB - To evaluate clinoptilolite, a natural zeolite, as a candidate material for a permeable reactive barrier for removal of strontium from groundwater, we investigated particle release and permeability reduction in clinoptilolite and sand porous media. In flow-through column experiments, we tested the effects of solution chemistry, grain size, and clinoptilolite pretreatment on particle release and hydraulic conductivity. Permeability reduction occurred not in the clinoptilolite itself but only in finer-grained sand down-gradient of the clinoptilolite. Solutions of high ionic strength inhibited particle release and prevented clogging. Clinoptilolite of larger grain size produced slightly less particle release and clogging. Two pretreatments of the clinoptilolite, rinsing to remove fine particles and calcining to improve strength, reduced particle release and clogging. Calcining, however, significantly reduced the strontium binding strength of the clinoptilolite. PMID- 11757609 TI - Kinetic model and optimization of 2,4-D degradation by anodic Fenton treatment. AB - Anodic Fenton treatment (AFT) is a new technology derived from chemical Fenton treatment. It has several advantages as compared with classic Fenton treatment and electrochemical Fenton treatment. On the basis of assumptions about a second order reaction between pesticides and hydroxyl radicals and about AFT technology, a new kinetic model was developed to accurately describe the degradation kinetics of 2,4-D and to quantitatively investigate the effect of operating conditions. 2,4-D (2,4-dichlorophenoxyacetic acid) was employed as a probe in this study to investigate the AFT system. It was found that an increased delivery rate of Fenton reagent increased the degradation rate of 2,4-D, but the efficiency was decreased. The effects of the H2O2:Fe2+ ratio, the temperature, the initial concentration of 2,4-D, and the presence of other organic compounds have also been investigated. Quantitative correlations have been established that allow the use of this technology as a controlled Fenton reaction to determine the reaction rate constants of other compounds with hydroxyl radicals easily and accurately. PMID- 11757610 TI - XAS studies of Ni and Zn sorbed to hydrous manganese oxide. AB - Adsorption mechanisms of Zn2+ and Ni2+ on hydrous manganese oxide (HMO) were investigated using XAS. Analyses reveal that both metal ions retain their primary hydration shell when sorbed to HMO, which is consistent with physical sorption. These local structures are invariant of pH (3.0-7.0) and adsorbate loading (10( 4) - 10(-2) mol (g of HMO)-1), suggesting one average type of adsorption mechanism. In addition to the first shell, a second shell was observed with 6-8 O atoms at 3.34 A for Ni and 8-10 O atoms at 3.49 A for Zn. The lack of Ni or Zn contributions in the second shell eliminates the possibility of surface precipitation or polymerization. Likewise, the absence of Mn atoms in the second shell suggests outer-sphere adsorption. Interestingly, the local structure of Ni and Zn sorbed to HMO did not change with reaction time when as much as 90% of the sorbed contribution was due to the slow sorption process, thus supporting intraparticle diffusion as the rate-limiting mechanism. This result demonstrates that adsorption sites located along the micropore walls of HMO are similar to ones located on the external surface. Overall, metals from the same group in the Periodic Table appear to form similar adsorption complexes with HMO. PMID- 11757611 TI - Novel model describing trace metal concentrations in the earthworm, Eisenia andrei. AB - We developed a novel model describing Eisenia andrei body concentrations for Cd, Cu, Pb, and Zn as a function of pH, metals, and soluble organic carbon (SOC) in soil extracts for potential use in predicting values in contaminated field sites. Data from 17 moderately contaminated Dutch field soils in which earthworms were cultured were used in model development. Model parameters quantify biological phenomena important for metal bioavailability, and soil variables quantify relevant soil chemistry characteristics. Earthworm body concentration (EBC) was modeled so that soil metal soluble at bulk soil pH was considered available for dermal exposure, and gut exposure was due to soil metal in solution near neutral regulated gut pH. The efficiency parameter values indicated that metals are biologically regulated in the following order (most to least): Zn - Cu > Pb > Cd. The values determined for the exposure-route constant indicate that Cd, Cu, and Pb EBCs are almost exclusively (>96%) due to dermal exposure and that only 18% of Zn EBC was due to gut exposure. The minimum healthful EBCs determined were Zn > Cu > Pb > Cd, and the values for Pb and Cd were near zero. The Cu model was normalized by soluble organic carbon to be meaningful. The model was most accurate in describing Zn behavior. PMID- 11757612 TI - DGT as an in situ tool for measuring radiocesium in natural waters. AB - The application of diffusive gradients in thin-films (DGT) samplers for the measurement of cesium radionuclides in solution, using an ammonium molybdophosphate (AMP) binding agent, was tested under both laboratory and field conditions. In the former they proved able to reproduce known 134Cs concentrations (60 Bq L(-1)) with a high degree of accuracy and precision over periods up to approximately 1 d, in freshwaters over a wide range of pH and temperature, and in saline water. In field trials in a freshwater lake receiving nuclear power station discharges, mean concentrations of 137CS (47-61 mBq L(-1)) were measured over periods from 5 d to 1 month. These agreed, within error, with mean concentrations determined from grab samples but rigorous field validation of long-term (month) deployments of DGT devices proved impossible using conventional sampling procedures, due to loss of 137Cs to container walls. Identified limitations of the DGT technique included probable AMP degradation over longer periods and calibration problems if large changes in temperature and concentration occurred together. Potential limitations due to biofilm growth were considered not to be significant. Despite the limitations, the technique appears to measure concentrations accurately for deployment times of 1 month or less. It has several advantages over traditional sampling methods for monitoring radionuclides in the solution/dissolved phase, including its simplicity, provision of time-averaged mean concentrations, and automatic in-situ concentration onto a medium with ideal counting geometry for gamma spectrometry. PMID- 11757613 TI - Further developments in the use of semipermeable membrane devices as passive air samplers: application to PCBs. AB - There are several incentives for developing passive air sampling techniques for persistent organic pollutants (POPs). This paper reports on studies to further calibrate and optimize semipermeable membrane devices (SPMDs) for use as "integrated" air samplers of gas-phase POPs. These samplers are deployed over weeks/months/years. Polychlorinated biphenyls (PCBs) were used as the test compounds in this study, with three specific objectives: (i) to determine whether ambient wind speed limits the rate of uptake during typical deployment conditions; (ii) to monitor uptake and SPMD-air equilibrium for a range of compounds; and (iii) to assess the application of performance reference compounds (PRCs) in air sampling, to "correct" for site-specific differences in uptake rates. When deployed in Stevensons screens under ambient conditions, wind speed did not significantly affect uptake rates. Rather, differences in summer/winter uptake rates reported previously, using the same deployment devices as here, are due to temperature affecting compound permeability through the membrane. Results from the use of PRCs indicate that SPMDs should be spiked prior to exposure with a range of compounds that are not present in the atmosphere, so that uptake rates can be estimated from depuration rates during a particular deployment. Short-term deployments (e.g. days; few weeks) would need to use compound(s) with a low octanol:air partition coefficient (K(OA)) (e.g. 13C12 labeled PCB-28); long-term deployments (of many months to years) would need to use intermediate K(OA) compounds (e.g. 13C12 PCB-101; 13C12 PCB-153). PMID- 11757614 TI - Subnanomolar detection of acid-labile sulfides by the classical methylene blue method coupled to HPLC. AB - Methylene blue reactive sulfides (MBRS) are ubiquitous in surface waters of local lakes and streams. However, in most cases they exist in concentrations too low to measure by traditional methods. Both the classical methylene blue and the similar Cline method have been used to determine concentrations of a particular pool of acid-labile sulfides in aquatic systems. The estimated lowest limit of MBRS detection is ca. 10 nM under ideal conditions. By coupling the classical methylene blue method to HPLC, it is possible to make direct, reliable measurements of MBRS in fully oxygenated freshwaters. Using this modified approach, a detection limit for MBRS of ca. 0.3 nM is achieved. Measurements in a variety of local freshwaters reveal levels in the range of 0-74 nM, with systematic variations explainable in terms of standard biogeochemical characteristics. PMID- 11757615 TI - Evaluation of environmental effects on metal transport from capped contaminated sediment under conditions of submarine groundwater discharge. AB - Previous studies conducted in our laboratories have shown that submarine groundwater discharge (SGD) can significantly increase metal fluxes from capped contaminated sediment to the overlying water. Five columns were set up in the laboratory to evaluate the effects of environmental factors such as groundwater pH, sediment depth, and groundwater flow rate on metal transport from capped contaminated sediment under conditions of SGD. Acidified groundwater discharge was shown to enhance the mobility of all tested metals except Mo. Although much of the released metal was adsorbed by the capping material, significant increases of initial or steady-state fluxes to the overlying water were observed for Ni, Cu, Zn, Cd, Pb, and Mn. Additional sediment depth enhanced steady-state fluxes for all tested metals except Mo, Cd, and Pb. Increased SGD rates did not significantly change the average metal concentration in the outflow to the overlying water for most metals; however, all metal releases were higher due to the greater flow at increased SGD rates. The residence time and the redox conditions may be important in evaluating environmental effects on capping efficiency. PMID- 11757616 TI - Sorption mechanisms of zinc to calcium silicate hydrate: sorption and microscopic investigations. AB - Knowledge of the binding mechanisms of heavy metals to cement minerals is essential for the prediction of the long-term leachability of secondary building materials and cement-stabilized wastes containing heavy metals. In this study, the sorption of Zn(II) to calcium silicate hydrate (C-S-H(I)) in pre-equilibrated aqueous suspensions has been investigated as a function of time (up to 87 d), pH (11.7, 12.48, and 12.78) and Zn(II) concentration (4.8-4800 microM). Electron probe microanalysis (EPMA) was performed in order to determine where Zn(II) was bound. At high Zn(II) concentrations (>1000 microM), the precipitation of beta2 Zn-(OH)2 (< pH 12) and calcium zincate (Zn2Ca(OH)6 x 2H2O, > pH 12) was observed. Surface precipitation could not be discerned. At lower concentrations, it was found that the sorption process was initially very rapid with over 50% sorbed within 30 min but that the sorption continued more slowly to at least 87 d. The data could be interpreted in terms of the Freundlich isotherm up to a Si:Zn(II)sorbed atomic ratio of approximately 6:1. Zinc was observed by EPMA to incorporate into the C-S-H(I) particles but did not appear to substitute for Ca or Si. The incorporation of Zn(ll) in the interlayer of C-S-H(I) or sorption to internal surfaces of crystalline appear to be the most probable mechanisms for the observed Zn(II) sorption to C-S-H(I). PMID- 11757617 TI - Arsenate and arsenite removal by zerovalent iron: effects of phosphate, silicate, carbonate, borate, sulfate, chromate, molybdate, and nitrate, relative to chloride. AB - Batch tests were performed to evaluate the effects of inorganic anion competition on the kinetics of arsenate (As(V)) and arsenite (As(III)) removal by zerovalent iron (Peerless Fe0) in aqueous solution. The oxyanions underwent either sorption dominated reactions (phosphate, silicate, carbonate, borate, and sulfate) or reduction-dominated reactions (chromate, molybdate, and nitrate) with Peerless Fe0 in the presence of As(V) or As(III), relative to chloride. Pseudo-first-order rate equations were found to describe satisfactorily both As(V) and As(III) removal kinetics in the presence of each competing anion. Of the oxyanions tested for Peerless Fe0 in the pH range from 7 to 9, phosphate caused the greatest decrease in As removal rate (7.0 x 10(-3) to 18.5 x 10(-3) h(-1)) relative to chloride (34.9 x 10(-3) to 36.2 x 10(-3) h(-1)). Silicate, chromate, and molybdate also caused strong inhibition of As removal, followed by carbonate and nitrate, whereas borate and sulfate only caused slight inhibition to As(III) removal. Present results show that Peerless Fe0 may be an excellent permeable reactive barrier medium for a suite of mixed inorganic contaminants. The anion competing effects should be considered when designing permeable reactive barriers composed of zerovalent iron for field applications to remediate As(V) and As(III). PMID- 11757618 TI - Factors controlling alkylbenzene sorption to municipal solid waste. AB - The sorption of toluene and o-xylene to individual municipal solid waste (MSW) constituents [office paper, newsprint, model food and yard waste, high density polyethylene, and poly(vinyl chloride) (PVC)] was evaluated. Effects of sorbent decomposition and solvent composition on alkylbenzene sorption were studied by evaluating biodegradable sorbents in both fresh and anaerobically decomposed form and by complementing single-solute isotherm tests with experiments conducted in acidogenic and methanogenic leachate. Alkylbenzene sorption to plastics was greaterthan to biopolymer composites, and differences in sorbate/sorbent solubility parameter compatibility explained this observation. Alkylbenzene sorption to biopolymer composites yielded linear isotherms, and sorption capacities [log(Koc/Kow)] decreased linearly with increasing sorbent polarity as expressed by the O-alkyl/alkyl ratio. Leachate composition had little effect on alkylbenzene sorption with one exception; volatile fatty acids in acidogenic leachate appeared to convert PVC from a glassy to a rubbery polymer. The results of this study showed that sorbent organic matter affinity for hydrophobic organic contaminants (HOCs) increases with increasing extent of MSW decomposition because of the recalcitrance of plastics and the preferential degradation of polar biopolymers. Furthermore, the plasticizing effect of volatile fatty acids in acidogenic leachate may enhance the bioavailability of HOCs sorbed to glassy organic matter in MSW or in soils contaminated with acidogenic leachate. PMID- 11757619 TI - PAH release during water desorption, supercritical carbon dioxide extraction, and field bioremediation. AB - Removal rates of polycyclic aromatic hydrocarbons (PAHs) from manufactured gas plant (MGP) soils were determined using water desorption for 120 days and mild supercritical carbon dioxide extraction (SFE) for 200 min. Both techniques were used to compare the changes in desorption rates for individual PAHs from untreated and treated soils that were obtained from a field biotreatment unit after 58, 147, and 343 days. Water desorption profiles (plotted in days) and SFE profiles (plotted in minutes) were very similar regardless of whether a PAH was rapidly or slowly removed. Water and SFE profiles were fit with a simple two-site (fast and slow) model to obtain the fraction of each PAH that was rapidly released (F). There was agreement between the F values obtained from water desorption and SFE for PAHs ranging from naphthalene to benzo[a]pyrene from all soils, with an overall correlation coefficient (r2) of 0.81. F values from water desorption and SFE also agreed with the actual removal of PAHs obtained after 147 and 343 days of field remediation (r2 ca. 0.80). The use of shorter desorption times (2-4 days for water and 20-40 min for SFE) allowed F values to be estimated for all PAHs and showed excellent agreement with the removal of individual PAHs obtained with 147-343 days of field remediation (r2 > 0.9). The comparisons indicate that short-term SFE can provide a reasonable estimate of the fraction of a PAH that is readily released and available for microbial treatment. PMID- 11757620 TI - Genetics of COPD: present and future. PMID- 11757621 TI - Infection: friend or foe to the development of asthma? PMID- 11757622 TI - Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease. AB - Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue inhibitor of metalloproteinases-2 (TIMP-2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix. Polymorphisms of the TIMP-2 gene were investigated in 88 COPD patients and 40 control subjects. The variations were examined by single-strand conformational polymorphism analysis followed by sequencing. Two polymorphisms were identified, +853 GIA and -418 G/C nucleotide substitutions. There was a significant deviation in the genotypic frequencies at +853 and the allele frequencies for G were significantly higher in the COPD patient group than in the control group. For locus -418, the allele frequencies for C in the COPD patient group also tended to be higher than those in the control group. The +853 G/A nucleotide substitution was a silent variant. The 418 G/C substitution was located in the consensus sequence for the Sp1 binding site. These polymorphisms may be associated with the development of chronic obstructive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibility to the disease. PMID- 11757623 TI - Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis. AB - Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and-control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*IF homozygotes was 2.2 (95%, confidence interval 1.1-4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozvgotes, GC*2-1F heterozygotes, GC*2 1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*IF gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found. PMID- 11757624 TI - GENebu Project: home nebulizer use and maintenance in Italy. AB - Due to the lack of information on this topic, the Educational Group of the Italian Association of Hospital Pneumologists performed an open, multicentre, observational survey to evaluate home nebulizer practices in Italy. From May December 1999, all patients attending one of the 27 participating chest clinics throughout Italy and who were or had been using a home nebulizer in the previous 6 months were consecutively enrolled. All patients completed a self-administered questionnaire on their current practices of home nebulization. Of the 1,721 questionnaires delivered, 1,257 were returned with an overall response rate of 73%. Most patients (82.8%) reported using their nebulizer for bronchopulmonary symptoms and the remaining patients only used theirs for upper respiratory tract diseases. Subjects using their nebulizer for lower respiratory symptoms were older (p<0.001), predominantly female (p<0.001) and used their nebulizer more frequently (p<0.001). Forty per cent of patients >60 yrs old used their nebulizer regularly, at least once a day. More than 60% of respondents never received any information from healthcare workers on the correct usage of their nebulizer, and >75% received no information on nebulizer hygiene and care. Patients who received information on the use and maintenance of their nebulizer from caregivers more commonly attended to these practices (p<0.01). The present survey suggests that home nebulizer use and maintenance in Italy are heterogeneous, and there is the need to implement better nebulizer practice. PMID- 11757625 TI - Reference values for alveolar membrane diffusion capacity and pulmonary capillary blood volume. AB - The reference values for diffusion capacity of the alveolar capillary membrane (Tm,CO) and pulmonary capillary volume (Qc) are scarce, while the standard deviations of the equations are large. New equations and residual standard deviations (RSDs) were determined in a sample of healthy subjects. Tm,CO and Qc values were measured in 117 (72 females, 45 males) nonsmoking healthy subjects. The carbon monoxide transfer factor (TL,CO) was determined when the volunteer was breathing room air and subsequently, when the volunteer was breathing 100% oxygen. From these data, Tm,CO and Qc values were calculated. The females' TL,CO was 3.15 mmol x min(-1) x kPa(-1) lower than the males', apparently caused by lower female lung volume. Tm,CO and Qc were lower in females, but correction for lung volume eliminated this difference. Qc(-1) reference equations for females and males, respectively, are 4.375 x 10(-2) - 1.085 x l0(-2) x height and 4.455 x 10(-2) -1.085 x 10(-2) x height (RSD for both sexes: 2.544 x 10(-3)). Tm,CO(-1) reference equations for females and males, respectively, are 0.111+3.304 x 10(-4) x age-4.753 x 10(-2) x height and 0.127+3.304 x 10(-4) x age-4.753 x 10(-2) x height (RSD for both sexes: 1.085 x 10(-2)). The general character of these equations complies with earlier publications, the only difference being that the RSDs are 1.18-2.76 times lower. New reference equations for diffusion capacity of the alveolar capillary membrane and pulmonary capillary volume are available with considerably smaller residual standard deviations. PMID- 11757626 TI - Forced spirometry reference values for Norwegian adults: the Bronchial Obstruction in Nord-Trondelag Study. AB - The purpose of this study was to develop new prediction equations for flow/volume spirometry parameters in asymptomatic, never-smoking adults in Norway, and to assess any differences of these parameters when applying the new and most commonly used equation sets. Flow/volume spirometry was measured according to the American Thoracic Society criteria in 2,792 subjects aged > or = 20 yrs, randomly selected from participants in the Nord-Trondelag Health Study. Ever-smokers and subjects with respiratory symptoms and/or diseases reported in this questionnaire were excluded. A total of 546 females and 362 males met the inclusion criteria and were included in the analyses. Most lung function variables were nonlinear by age and had to be transformed. After a plateau in younger adults, the variables declined by age. The reference values for forced expiratory volume in one second and forced vital capacity from the present study, were higher than those given by prediction equations from the European Community for Coal and Steel, but in closer agreement with later studies from Europe, Australia and the USA. Healthcare providers should be encouraged to reconsider their choice of prediction equations of spirometry in order to improve management of obstructive lung diseases. PMID- 11757627 TI - Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers. AB - Aerosol delivery depends on device design and inhalation technique. In vitro device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus it and Turbuhaler it inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus and Turbuhaler, were significantly correlated. The r-values were 0.865 and 0.882, respectively (p<0.01). Percentage explained variance was 74.8% for Diskus and 77.8% for Turbuhaler. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups. PMID- 11757628 TI - The impact of meconium ileus on the clinical course of children with cystic fibrosis. AB - The present study was designed to compare the clinical course of children diagnosed with cystic fibrosis (CF) in infancy due to the presence of meconium ileus (MI) with children diagnosed by way of a newborn screening programme (non MI). A matched case-control study design was used. Matching was performed on the basis of sex and date of birth. All children born in New South Wales, Australia after 1980 and who had attended the CF clinic at The Children's Hospital at Westmead since diagnosis were included as possible cases or controls. Parameters pertaining to the clinical course were compared in 39 matched pairs. MI children had a significantly worse pulmonary status. The forced expiratory volume in one second was 16.3 +/- 5.2% higher (p<0.001, n=21 pairs) and the forced vital capacity value 10.5 +/- 4.7%, higher (p<0.05, n=21 pairs) in non-MI children. The difference between the pairs (18.6 +/- 4.4 MI and 20.5 +/- 3.4 non-MI) in the Shwachman chest radiograph score was statistically significant (p<0.05, n=39 pairs). There were no significant differences in any other assessed parameters, such as height, weight, the presence of liver function abnormalities, the frequency of hospitalization or airway microbial colonization. Meconium ileus may be an early indication of a more severe phenotype of cystic fibrosis. This was suggested by the significantly lower pulmonary function found in children with a history of meconium ileus compared to age- and sex-matched children who did not have meconium ileus. PMID- 11757629 TI - Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children. AB - The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-h intraoesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9 +/- 3.5 (mean +/- SEM) which were higher than LLI in healthy adults (1.0 +/- 0.4), (p=0.045). Children with CF had very high LLIs (19.2 +/- 4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction. PMID- 11757630 TI - Epidermal growth factor in the lungs of infants developing chronic lung disease. AB - Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg x mL(-1), p<0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease. PMID- 11757631 TI - Anti-inflammatory effect of adenovirus-mediated IkappaBalpha overexpression in respiratory epithelial cells. AB - Many studies into basic biological characteristics of inflammation and tissue injury have implicated pro-inflammatory cytokine-mediated tissue injury in the pathogenesis of inflammatory lung diseases. Because transcription of most proinflammatory cytokines is dependent on the activation of nuclear factor (NF) kappaB, NF-kappaB could be a good potential target to suppress the cytokine cascade. Cytokine-induced activation of NF-kappaB requires phosphorylation and subsequent degradation of IkappaBa. Therefore, the blocking NF-kappaB activation by IkappaBalpha could inhibit the pro-inflammatory cytokine-induced tissue injury. To evaluate whether blocking of NF-kappaB activation shows an anti inflammatory effect, this study investigated the effect of adenovirus-mediated overexpression of IkappaBalpha super-repressor (IkappaBalpha-SR) on the pro inflammatory cytokine expression in respiratory epithelial cells. The transduction efficiency of adenovirus was >90% in both A549 and NCI-H157 cells. Ad5IkappaBalpha-SR-transduced cells expressed high levels of IkappaBalpha-SR, which was resistant to tumour necrosis factor (TNF)-alpha-induced degradation. Adenovirus-mediated overexpression of IkappaBalpha-SR blocked cytokine-induced nuclear translocation of p65 and NF-kappaB deoxyribonucleic acid binding activity without affecting total cellular expression level of NF-kappaB. Ad5IkappaBalpha SR transduction suppressed cytokine-induced interleukin-8 and TNF-alpha expressions at both ribonucleic acid and protein levels. These results suggest that blocking the nuclear factor-kappaB pathway by adenovirus-mediated overexpression of IkappaBalpha-super-repressor shows an effective anti inflammatory effect in respiratory epithelial cells. PMID- 11757632 TI - Effect of luminal osmolarity on ion content of connective tissue in rat trachea after epithelial damage. AB - The authors investigated the physical role of the airway epithelium in response to changes in the airway surface fluid's composition by superperfusing the lumen with nonisotonic solutions. Morphological studies and measurements of changes in ion content in the underlying connective tissue (CT) were carried out. The study used an experimental model of isolated rat trachea. The trachea was mounted in an extraluminal organ bath with Ringer's solution, whereas the lumen was perfused with a fluid in which the NaCl concentration was varied. The tissue was fixed for electron microscopy or frozen for X-ray microanalysis. X-ray microanalysis showed that the Na and Cl content of the CT increased with increasing luminal NaCl concentrations. This increase was significantly larger when the tight junctions had been damaged by exposure to ethylene glycol tetra-acetic acid. At high luminal NaCl concentrations, electron microscopy showed that a significant influx of fluid into the CT had occurred in tracheae with damaged epithelia. Damage to the epithelium also resulted in ultrastructural changes in myofibroblasts, increased diameter of capillaries, and thickening of the basement membrane. The epithelium evidently plays a crucial role in the regulation of the ion content of the connective tissue in the airway wall, and epithelial damage may explain the greater sensitivity to provocation with hyperosmolar sodium chloride solutions or airway dehydration observed in patients with asthma or cystic fibrosis. PMID- 11757633 TI - A new method to perform quantitative measurement of bronchoscopic images. AB - Bronchoscopy is a commonly used clinical tool that provides a direct image of the bronchial lumen. However, bronchoscopy has seen little use as a quantitative measurement tool, mainly because of the wide-angle lens which distorts the image. The present authors have tested the ability of numerical algorithms and commercial software to correct for this distortion. Test objects of known size were imaged with four different bronchoscopes. Commercial image analysis software was used to measure the size of features in the images before and after applying distortion correction algorithms. The technique was then applied by measuring airway narrowing in anaesthetized pigs during vagal stimulation. Without correction, object size near the edge of the field of view is underestimated by approximately 40%. The error in measured diameter of concentric circles was dependent on the radius of the circle, increasing to 25% for circles occupying 90% of the field. Third order polynomial functions were required to correct these errors. After correction, errors were independent of object size or location in the image. Correction for lens distortion was independent of the distance between bronchoscope and object. The authors conclude that modern image processing software can correct for the distortion produced by wide-angle bronchoscope lenses. PMID- 11757634 TI - Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury. AB - The aim of this study was to determine the role of matrix metalloproteinases (MMPs) in the pathogenesis of acute lung injury induced by hyperoxia. Twenty three pigs were exposed in sealed cages to >80% oxygen (for 24-120 h) or room air. Correlation between MMP-2/MMP-9 activity, measured by gelatin zymography in bronchoalveolar lavage fluid (BALF), and the histological findings and pathological parameters were examined in detail. Sources of these MMPs in the hyperoxic lung were analysed by immunohistochemistry. The histological progression of acute lung injury in this model ranged from the early exudative to the early proliferative phase of diffuse alveolar damage (DAD). MMP-2 and -9 activities were elevated under prolonged hyperoxic exposure. MMP-9 activity correlated significantly with the oxygen tension in arterial blood/inspiratory oxygen fraction, the lung wet-to-dry weight ratio, and the number of neutrophils in BALF, whereas MMP-2 activity did not correlate at all with these factors. MMP 9 activity correlated more closely with the pathological findings of DAD than did MMP-2 activity. Strong MMP-9 expression was observed in neutrophils, alveolar macrophages as well as alveolar lining epithelial cells. These results suggest that matrix metalloproteinase. which may derive from neutrophils recruited into airspaces, plays an important role in the pathogenesis of hyperoxic diffuse alveolar damage PMID- 11757635 TI - Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension. AB - Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-2 and MMP-9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, specific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension. PMID- 11757636 TI - Role of T- and B-lymphocytes in pulmonary host defences. AB - Pulmonary infectious diseases cause significant morbidity and mortality in both industrialized and developing countries. Adaptive immune responses are required to defend the lung against pathogens that survive in normal macrophages and extracellular organisms that evade phagocytosis. Microbes initiate both innate immune responses and specific adaptive immune responses. Innate immune response molecules regulate T-lymphocyte differentiation. Activated T-lymphocytes provide cytokines, which activate macrophages and lytic signals that lyse infected antigen-presenting cells. Antibodies produced by plasma cells facilitate microbial clearance through diverse effector mechanisms including opsonization, complement fixation and antibody-dependent cytotoxicity. Lymphocytes determine the specificity of the immune response and orchestrate effector limbs of the immune response. PMID- 11757637 TI - Lung cancer screening by low-dose spiral computed tomography. AB - The poor prognosis of lung cancer has barely changed in the last decades, but the prognosis is better when the disease is detected earlier. Lung cancer screening by chest radiography did not lead to a decrease in lung cancer mortality, presumably because the chest radiograph is a poor screening tool with low sensitivity. With the advent of the low-dose spiral computed tomography (CT) scan it has become feasible to detect early invasive stage I lung cancer in 8-90% of cases. This technique could possibly decrease lung cancer mortality, but the extent of this effect is as yet unknown, and whether lung cancer screening will be cost-effective is yet to be determined. These questions can only be resolved in a randomized controlled trial with lung cancer mortality as an unbiased end point. In this review, the initiatives to evaluate low dose spiral CT screening for lung cancer in Japan, USA and Europe are presented. In the USA and Japan, evaluation is in one-armed studies, whereas in many European countries randomized trials are now being planned and several one-armed studies have been initiated. A formal collaboration among these countries has now been set up. It is strongly recommended that lung cancer screening be evaluated in randomized trials in order to allow evidence-based health policy decisions to be made on this subject. PMID- 11757638 TI - Advances in imaging. AB - In recent years there have been major advances in chest imaging. These include significant refinements in previously available techniques such as computed tomography (CT) and magnetic resonance (MR) imaging and the introduction of new techniques into the clinical armamentarium, particularly positron emission tomography (PET) imaging. These advances have led to changes in the diagnostic approach to a number of conditions, particularly pulmonary embolism, lung cancer, diseases of the large and small airways, and diffuse lung disease. They have also brought new insights into the pathophysiology of lung disease. State of the art CT and MR imaging now allow objective quantification of lung disease and assessment of regional changes in ventilation and perfusion caused by airway and parenchymal abnormalities. The aim of this article is to summarize the most important clinical applications of the recent advances in imaging and to emphasize the topics of imaging research likely to attract particular attention from radiologists and clinicians in the near future. PMID- 11757639 TI - Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence. AB - There is increasing evidence from epidemiological studies to support the "hygiene hypothesis" with regard to the development of allergic diseases. This review will discuss the epidemiological findings relating to atopy and asthma, separately. The strongest arguments in favour of the "hygiene hypothesis" are the findings relating early life day care attendance to a significantly reduced risk of atopy and asthma, and the strong link between sibship size and the occurrence of atopy as confirmed by numerous studies. Furthermore, data relating serological immune responses to certain infections such as hepatitis A and Toxoplasma gondii suggest a role for such infections, or alternatively the lack of hygiene, to be operative in the inhibition of the development of allergic immune responses. The effects described seem to be stronger for atopy than for asthma. Furthermore, biological plausibility for such a hypothesis can be found from findings of recent in vitro studies and from animal experiments. Epidemiological studies attempting to identify single infections as being harmful or beneficial could fail, because it may be the total burden of microbial stimuli rather than a certain infection that directs the maturing immune system into a Th1-type T-helper cell polarized response. The timing of the exposure seems to be essential for promoting beneficial or harmful effects, and may provide a "window of opportunity". PMID- 11757640 TI - Identification of disease genes by expression profiling. AB - The human genome has been completely sequenced. The development of innovative methodologies and tools to understand the functions of human genes in health and disease will allow the data of the human genome project to be utilized. This paper reviews methods that can be used to detect and isolate genes that are specifically expressed in certain diseases or that are specific to cell types. First, classical methods, such as differential screening of complementary deoxyribonucleic acid libraries and subtractive techniques, are described. Methods based on polymerase chain reaction (PCR), such as differential display PCR or serial analysis of gene expression, will then be discussed. Finally, recent developments in gene chip technology and basic principles of functional genomics will be illustrated. Future developments will link the results of genomic approaches to data obtained by other systematic methods, such as proteomics (i.e. the systematic, large scale analysis of proteins), and will allow the production of a detailed molecular characterization of diseases, disease stages, tissues, or cell types. Methods to detect disease or cell type specific gene expression patterns will play an important role in the future of basic research, as well as the development of novel diagnostic procedures and identification of therapeutic targets. PMID- 11757641 TI - Pulmonary toxicity with mefloquine. AB - This report presents a case of acute lung injury developing within hours after administration of mefloquine for a low-level Plasmodium falciparum malaria, which was persistent despite halofantrine therapy. Extensive microbiological investigation remained negative and video-assisted thoracoscopic lung biopsy demonstrated diffuse alveolar damage. The evolution was favourable without treatment. This is the second report of acute lung injury and diffuse alveolar damage caused by mefloquine. Glucose-6-phosphate dehydrogenase deficiency was present in the former case and was thought to contribute to the lung injury. However, glucose-phosphate dehydrogenase was normal in the present case, suggesting that it is not a predisposing condition to the lung injury. PMID- 11757642 TI - Carbon monoxide transfer coefficient KCO (TL/VA): a flawed index. PMID- 11757643 TI - Lung biopsy in patients with usual interstitial pneumonia. PMID- 11757644 TI - Examples of hula-twist in photochemical cis- trans isomerization. AB - ALiu and Hammond recently reasoned that the hula-twist (HT), a volume-conserving cis-trans isomerization mechanism, is involved in reactions of confined systems. We now show that HT can be applied to various reported photochemical isomerization of chromophores (small organic systems as well as photoactive bio pigments). The results, when taken as a whole, argue powerfully that HT is a common supramolecular photoisomerization reaction mechanism. PMID- 11757645 TI - Using sonochemical methods for the preparation of mesoporous materials and for the deposition of catalysts into the mesopores. AB - Ultrasound radiation can be used to synthesize a variety of mesporous materials. The reaction time is considerably shorter than the conventional methods. Ultrasonic waves can be further used for the insertion of amorphous nanosized catalysts into the mesopores. A detailed study demonstrates that the nanoparticles are deposited as a monolayer on the inner mesopores walls without blocking them. When the ultrasonically prepared catalyst/mesoporous-subtrate composite is used in catalysis a high conversion into product is obtained. PMID- 11757646 TI - Mechanism for formation of the lightstruck flavor in beer revealed by time resolved electron paramagnetic resonance. AB - Time-resolved electron paramagnetic resonance (TREPR) data collected during the photodegradation of iso-a-acids (isohumulones), the principal bittering agents from hops in beer, are presented and discussed, and, from the data, the photophysics leading to free-radical production as the primary step in the photodecomposition of iso-alpha-acids towards the development of "skunky" beer are explained. During laser flash photolysis of iso-alpha-acids at 308 nm in toluene/methylcyclohexane (1:1), TREPR spectra exhibit net emissive signals that are strongly spin polarized by the triplet mechanism of chemically induced electron spin polarization. From two potential photochemically active sites, the TREPR data show that although the first site, an enolized beta-triketone, is the primary light-absorbing chromophore, an uphill intramolecular triplet energy transfer process leads to Norrish type I alpha-cleavage at a second site, an alpha-hydroxycarbonyl. The energy transfer mechanism is supported by additional TREPR experiments with chemically modified hop compounds. Structural parameters (hyperfine coupling constants, g factors, line widths) for the observed free radicals, obtained from computer simulations, are presented and discussed. PMID- 11757647 TI - Biocatalytic reduction of beta,delta-diketo esters: a highly stereoselective approach to all four stereoisomers of a chlorinated beta,delta-dihydroxy hexanoate. AB - A stereoselective chemoenzymatic synthesis of all four stereoisomers of tert butyl 6-chloro-3,5-dihydroxy-hexanoate (6a) is presented. The key step of the sequence is a highly regio- and enantioselective single-site reduction of tert butyl 6-chloro-3,5-dioxohexanoate (1a) by two enantiocomplementary biocatalysts. Alcohol dehydrogenase from Lactobacillus brevis (recLBADH) afforded a 72% yield of enantiopure tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate [(S)-2a]. The enantiomer (R)-2a was prepared with 90-94% ee by Baker's yeast reduction in a biphasic system (50% yield). Both biotransformations were performed on a gram scale. The beta-keto group of the enantiomeric delta-hydroxy-beta-keto esters 2a thus obtained was reduced by syn- and anti-selective borohydride reductions. Permutation of the reduction methods yielded all four stereoisomers of the crystalline target compound 6a (> or = 99.3% ee, dr > or = 205:1), which is a versatile 1,3-diol building block. recLBADH accepts a variety of beta,delta diketo esters as was determined in a photometric assay. tert-Butyl 3,5-dioxo hexanoate (1b) and tert-butyl 3,5-dioxo-heptanoate (1c) were reduced on a preparative scale as well to afford the corresponding delta-hydroxy-beta-keto esters (R)-2b and (R)-2c with 99.4% ee and 98.1% ee, respectively. PMID- 11757648 TI - Diene-Containing half-sandwich MoIII complexes as ethylene polymerization catalysts: experimental and theoretical studies. AB - Seventeen-electron compounds of MoIII having the general formula [(eta5 C5R5)Mo(eta4-diene)X2] (R = H, Me: dieney = butadiene, isoprene, or 2,3 dimethylbutadiene: X= Cl, CH3) are a new class of ethylene polymerization catalysts. The polyethylene obtained shows a bimodal distribution, the major weight fraction being characterized by very long (M around 10(6)) and highly linear polymer chains. The newly prepared pentamethylcyclopentadienyl (Cp*) derivatives are more active than the cyclopentadienyl (Cp) derivatives, but much less active than previously investigated niobiumIII compounds having the same stoichiometry. On the other hand, the turnover frequency of the active site leading to the high molecular weight chains is at least 10 times greater than that obtained with the corresponding Nb catalyst. The reason for the low activity is explained by a difficult activation process that is attributed to the low polarity and high strength of the Mo-alkyl bond. This is confirmed by a Mulliken charge analysis of density functional theory (DFT) geometry-optimized [CpM(eta4 C4H6)(CH3)2] (M = Nb, Mo) and by the calculation of the heterolytic bond dissociation energies. DFT calculations have also been carried out on the ethylene insertion coordinate for the [CpM(eta4-C4H6)(CH3)]+ model of the presumed active site. The results indicate an equivalent activation barrier to insertion for the Nb and Mo systems. Differences in optimized geometries for the reaction intermediates are attributed to the presence of the extra electron for the Mo system. This electron opposes the formation of M-H-C agostic interactions, while it strengthens the back-bonding M-ethylene interaction, but otherwise plays no active role in the polymer chain propagation mechanism. According to the calculations, the chain propagation for the Mo system occurs entirely on the spin doublet surface, the minimum energy crossover point with the quartet surface lying at a higher energy than the transition state for insertion on the doublet surface. PMID- 11757649 TI - Supercritical carbon dioxide as solvent and temporary protecting group for rhodium-catalyzed hydroaminomethylation. AB - Supercritical carbon dioxide (scCO2) acts simultaneously as solvent and temporary protecting group during homogeneously rhodium-catalyzed hydroaminomethylation of ethyl methallylic amine. Cyclic amines are formed as the major products in scCO,, whereas the cyclic amide is formed preferentially in conventional solvents. Multinuclear high-pressure NMR spectroscopy revealed that this selectivity switch is mainly due to reversible formation of the carbamic acid in the solvent CO2, which reduces the tendency for intramolecular ring closure at the Rh-acyl intermediate. These results substantiate the general concept of using scCO2 as a protective medium for amines in homogeneous catalysis and demonstrate for the first time its application for selectivity control. PMID- 11757650 TI - Synthesis and photophysical and cation-binding properties of mono- and tetranaphthylcalix[4]arenes as highly sensitive and selective fluorescent sensors for sodium. AB - The syntheses and properties of two calixarene-based fluorescent molecular sensors are reported. These comprise tert-butylcalix[4]arene either with one appended fluorophore and three ester groups (Calix-AMN1). or with four appended fluorophores (Calix-AMN4). The fluorophore is 6-acyl-2-methoxynaphthalene (AMN), which contains an electron-donating substituent (methoxy group) conjugated to an electron-withdrawing substituent (carbonyl group); this allows photoinduced charge transfer (PCT) to occur upon excitation. The investigated fluoroionophores thus belong to the family of PCT fluorescent molecular sensors. In addition to the expected red shifts of the absorption and emission spectra upon cation binding, a drastic enhancement of the fluorescence quantum yield-in an "off- on" fashion comparable to that seen in photoinduced electron transfer (PET) molecular sensors-was observed. For Calix-AMN1. it increases from 10(-3) for the free ligand to 0.68 for the complex with Ca2+. This exceptional behaviour can be interpreted in terms of the relative locations of the npi* and pipi* levels, which depend on the charge density of the bound cation. For Calix-AMN4. in addition to the photophysical effects observed for Calix-AMN1, interactions between the chromophores by complexation with some cations have been found in the ground state (hypochromic effect) and in the excited state (excimer formation). Steady-state fluorescence anisotropy measurements for the system Na+ is included in Calix-AMN4, show a depolarization effect due to energy transfer (homotransfer) between the fluorophores. Regarding the complexing properties, a high selectivity for Na+ over K+, Li+, Ca2+ and Mg2+ was observed in ethanol and ethanol-water mixtures. The selectivity (Na+/other cations) expressed as the ratio of the stability constants was found to be more than 400. PMID- 11757651 TI - Formation of novel photodimers from 4-aryl-1,4-dihydropyridines. AB - N-substituted 3-alkoxycarbonyl-4-aryl-1.4-dihydropyridines have been photochemically investigated for the first time. In contrast to reports of analogous 3,5-dialkoxycarbony] derivatives, they are unreactive in the solid state with shortest distances of potentially reacting double bonds of 6.883(3) A for one derivative examined by x-ray crystal structure analysis. Solution irradiation with unfiltered light (lambda > or = 270 nm) led to novel diazatetrakishomocubanes in 30-50% yields. Diazatetrakishomocubanes were also obtained by irradiation with filtered light (lambda > 313 nm) besides head-to tail connected syn-dimers. The irradiation of the syn-dimers with unfiltered light led to centrosymmetric cage dimers accompanied by some dimer fragmentation. Formation of the homocubanes via intermediate biradicals is supported by the available data. PMID- 11757652 TI - Pivalase catalytic antibodies: towards abzymatic activation of prodrugs. AB - Screening of monoclonal-antibody libraries generated against the tert-butyl phosphonate hapten 2 and the chloromethyl phosphonate hapten 3 with pivaloyloxymethyl-umbelliferone 1 as a fluorogenic substrate led to the isolation of eleven catalytic antibodies with rate accelerations around kcat/ kuncat = 10(3). The antibodies are not inhibited by the product and accept different acyloxymethyl derivatives of acidic phenols as substrates. The highest activity was found for the bulky, chemically less-reactive pivaloyloxymethyl group: there is no activity with acetoxymethyl or acetyl esters. This difference might reflect the preference of the immune system for hydrophobic interactions in binding and catalysis. Pivalase catalytic antibodies might be useful for activating orally available pivaloyloxymethyl prodrugs. PMID- 11757653 TI - Kinetics of the interaction of indium(III) with 8-quinolinol-5-sulfonic acid and with sulfate. AB - The kinetics and equilibria of indium(III) binding to 8-quinolinol-5-sulfonic acid (HQSA) have been investigated in acidic aqueous solution at 0.2 M ionic strength and 25 C by stopped-flow, absorption and fluorescence spectrometric methods. Absorption and fluorescence spectrometry revealed that a monoprotonated MHL3+ complex is formed in addition to the ML2+ chelate. The stability constants of the chelate (log K(ML) 6.53). of the monoprotonated complex (logK(MHL = 3.5l) and its acid dissociation constant (pK(C2) = 1.4) have been determined. Stopped flow measurements indicate three reaction paths that involve the interaction of M3+ with H2L+ (k1 =(3.21 +/- 0.04) x 10(2) m(-1) s(-1)), M3+ with HL (k2=(6.52 +/ 0.04) x 10(4) M(-1)s(-1)) and MOH2+ with HL (k3 = (1.60 +/- 0.08) x 10(6) M(-1) s(-1)), respectively. The reactivity of In3+ toward the uncharged form of HQSA has been found to be approximately two orders of magnitude less than expected based upon water exchange experiments. This behaviour has been explained with the assumption that the ligand is distributed between two forms (neutral and zwitterion) of which only the neutral form is reactive. The rate of complex formation between In3+ and SO4(2-) ion has been measured by the temperature-jump method with Tropaeolin 00 as the indicator. The second-order rate constant of the binding process is 5.1 x 10(4) M s(-1). This quantity yields a value for the first-order rate constant of 570 s(-1) for ligand penetration into the In3+ coordination shell, approximately two orders of magnitude less than normal. This finding is interpreted by the hypothesis that SO4(2-) forms a chelate with In3+ for which ring closure is the rate-determining step. PMID- 11757654 TI - Catalyst screening by electrospray ionization tandem mass spectrometry: Hofmann carbenes for olefin metathesis. AB - A new screening methodology, which combines in situ synthesis of complexes with an assay by electrospray ionization tandem mass spectrometry (ESI-MS), is introduced in order to investigate highly active, cationic ruthenium-carbene catalysts in ring-opening metathesis polymerization (ROMP). The parameter space, whic is defined by systematic variation of four structural features of the catalyst [[R2P(CH2),PR2-kappa2-P]XRu=CHR']+ (the halogen ligand, the diphosphane bite-angle, the steric bulk of the phosphane, and the carbene ligand) and the variation of the metathesis substrate, is mapped out. Chloride as the anionic ligand X, a small chelating angle (n = 1), and reduced steric demand of the substituents R (Cy versus tBu) lead to the most reactive complex in acyclic olefin metathesis, whereas variation of the carbene moiety CHR' has only a modest influence. The overall rate in the gas phase depends on the pi-complex preequilibrium and metallacyclobutane formation, which was found to be the rate determining step. In ROMP reactions backbiting has a profound influence on the overall rate. Moreover, we were able to establish that the reactivity trends determined in the gas phase parallel solution-phase reactivity. The overall rate in solution is also determined by a favorable dimer/ monomer preequilibrium providing the active catalyst by facile dissociation of dicationic, dinuclear catalyst precursors. PMID- 11757655 TI - Reactions of the allenylidenes trans-[IrCl[=C=C=C(ph)R](PiPr3)2] with electrophiles: generation of butatriene-, carbene-, and carbyne- iridium complexes. AB - The allenylidenciridium(I) complexes trans-[IrX(=C=C-CPh2)(PiPr3)2] (X = Cl: 1; X = I: 2) react with excess methyl iodide by C-C coupling and elimination of HI to give the eta2-butatriene compounds trans-[IrX-(eta2-CH2=C=C=CPh2)(PiPr3)2] (3, 4), of which 3 (X = Cl) was characterized by X-ray crystallography. Treatment of 1 and 5 (containing C=C=C(Ph)tBu as the allenylidene ligand) with HCI leads to the formation of the six-coordinate hydridoiridium(III) complexes [IrHCl2[= C=C=C(Ph)R](PiPr3)2] (6, 7) by oxidative addition at the metal center. In contrast, the reactions of 1 and 5 with both CF3CO2H and CF3SO3H afford the four coordinate vinylcarbene compounds trans-[IrCl[=C(X)-CH=C(Ph)R[(PiPr3)2] (8-10). For X= CF3CO2, in nitromethane a dissociation of the C-X bond occurs and the cationic iridium carbynes trans-[IrCl[=C-CH=C(Ph)R](PiPr3)2]+ are generated. Upon addition of NaBPh4, the stable carbyne complexes 11b (R= Ph) and 12b (R = tBu) with BPh4 as the counterion were isolated in almost quantitative yields. The X ray crystal structure analysis of 6 reveals that the chloro ligands are cis and the phosphane ligands trans disposed. PMID- 11757656 TI - Photo- and radiation-chemical formation and electrophilic and electron transfer reactivities of enolether radical cations in aqueous solution. AB - In aqueous solution, enolether radical cations (EE.+) were generated by photoionization (lambda < or = 222 nm) or by electron transfer to radiation chemically produced oxidizing radicals. Like other radical cations, the EE.+ exhibit electrophilic reactivity with respect to nucleophiles such as water or phosphate as well as electron transfer reactivity, for example, towards one electron reductants such as phenols, amines, vitamins C and E, and guanine nucleosides. The reactivity of these electron donors with the radical cation of cis-1,2-dimethoxyethene.+ (DME.+) can be described by the Marcus equation with the reorganization energy lambda = 16.5 kcalmol(-1). By equilibrating DME.+ with the redox standard 1,2,4-trimethoxybenzene, the reduction potential of DME.+ is determined to be 1.08 +/- 0.02 V/NHE. The oxidizing power of the radical cation of 2,3-dihydrofuran, which can be considered a model for the enolether formed on strand breakage of DNA, is estimated to be in the range 1.27-1.44 V/NHE. PMID- 11757657 TI - Oligosaccharide synthesis by coupled endo-glycosynthases of different specificity: a straightforward preparation of two mixed-linkage hexasaccharide substrates of 1,3/1,4-beta-glucanases. AB - Glycosynthases are engineered glycosidases which are hydrolytically inactive yet efficiently catalyse transglycosylation reactions of glycosyl fluoride donors, and are thus promising tools for the enzymatic synthesis of oligosaccharides. Two endo-glycosynthases, the E134A mutant of 1,3/1,4-beta-glucanase from Bacillus licheniformis and the E197A mutant of cellulase Cel7B from Humicola insolens, were used in coupled reactions for the stepwise synthesis of hexasaccharide substrates of 1,3/1,4-beta-glucanases. Because the two endo-glycosynthases show different specificity, towards laminaribiosyl and cellobiosyl donors, respectively, the target hexasaccharides were prepared by condensation of the corresponding disaccharide building blocks through sequential addition of the glycosynthases in a "one-pot" process. Different strategies were used to achieve the desired transglycosylation between donor and acceptor in each step, and to prevent unwanted elongation of the first condensation product and polymerization (self-condensation) of the donor: 1) selection of disaccharide donors differing in the configuration of the hydroxyl substituent normally acting as acceptor, 2) temporary protection of the polymerizable hydroxyl group of the donor, or 3) addition of an excess of acceptor to decrease the probability that the donor can act as an acceptor. The best procedure involved the condensation of alpha lactosyl or 4II-O-tetrahydropyranyl-alpha-cellobiosyl fluorides with alpha laminaribiosyl fluoride, catalyzed by E197A Cel7B, to give tetrasaccharide fluorides, which were then the donors for in situ condensation with methyl beta cellobioside catalyzed by E134A 1,3/1,4-beta-glucanase. After isolation, the final hexasaccharides Gal/beta4Glcbeta4Glcbeta3Glcbeta4Glcbeta4Glcbeta-OMe and Glcbeta4Glcbeta4Glcbeta3Glcbeta4Glcbeta4-Glcbeta-OMe were obtained in 70-80% overall yields. PMID- 11757658 TI - Substrate-Binding reactions of the 3[dsigma*psigma] excited state of binuclear gold(I) complexes with bridging bis(dicyclohexylphosphino)methane ligands: emission and time-resolved absorption spectroscopic studies. AB - The complexes [Au2(dcpm)2]-Y2 (dcpm = bis(dicyclohexylphosphino)methane; Y=ClO4 (1), PF6- (2), CF3SO3- (3), Au(CN)2- (4), Cl- (5), SCN (6) and I- (7)) were prepared, and the structures of 1 and 4-7 were determined by X-ray crystallography. Complexes 1-4 display intense phosphorescence with lambdamax at 360-368 nm in the solid state at room temperature as well as in glassy solutions at 77 K. The solid-state emission quantum yields of the powdered samples are 0.37 (1), 0.74 (2), 0.53 (3) and 0.12 (4). Crystalline solid 5 displays both high energy UV (lambdamax = 366 nm) and low-energy visible emissions (lambdamax = 505 nm) at room temperature, whereas either 6 or 7 shows only an intense emission with lambdamax at 465 or 473 nm, respectively. All the complexes in degassed acetonitrile solutions exhibit an intense phosphorescence with lambdamax ranging from 490 to 530 nm. The high-energy UV emission is assigned to the intrinsic emission of the 3[dsigma*psigma] excited state of [Au2(dcpm)2]2+, whereas the visible emission is attributed to the adduct formation of the triplet excited state with the solvent/counterion. The quenching rate constants of the visible emission of [Au2(dcpm)2]2+ in acetonitrile by various anions are 6.08 x 10(5) (ClO4-), 9.18 x l0(5) (PF6 ), 1.55 x 10(7) (Cl-) and 4.06 x 10(9) (I-) mol(-1) dm3s(-1). The triplet-state difference absorption spectra of 1-4 in acetonitrile show an absorption band with lambdamax at 350 nm and a shoulder/absorption maxima at 395-420 nm; their relative intensities are dependent upon the halide ion present in solution. Substrate binding reactions of the 3[dsigma*psigma] excited state with halide (X-) to give [Au2(dcpm)2X]+* would account for the lower energy absorption maxima in the triplet-state difference absorption spectra. With iodide as the counterion, complex 7 undergoes a photoinduced electron-transfer reaction with I- to give the radical anion I2-. PMID- 11757659 TI - Phalloidin synthetic analogues: structural requirements in the interaction with F actin. AB - Synthetic derivatives of phalloidin have been investigated in solution by circular dichroism (CD) and NMR spectroscopy. They differ from natural phalloidin (PHD). bicyclo(Ala1-D-Thr2-Cys3-cis-4-hydroxy-Pro4-Ala5-2-mercapto-Trp6 (OH)2Leu7)(S-3 --> 6), in that they are modified at positions 2, 3, and 7. Among these synthetic analogues, structural differences and varying degrees of atropisomerism are found. By comparing the respective molecular models obtained by restrained molecular dynamics (RMD) simulations based on experimental NMR data, structural features that may be responsible for the different biological behavior become apparent. Our results indicate that the structural changes that result from an inversion of chirality of residue 3 lead to a complete loss of toxicity. Conversely, toxicity is less affected by the structural changes that stem from an inversion of chirality of residue 2. Moreover, unlike the other phallotoxins, when the thioether unit bridges to the opposite face of the main peptide ring, in contrast to the situation in other phallotoxins, large structural changes are observed as well as a total loss of activity. Molecular models of the synthetic phalloidin analogues have been used to investigate the necessary structural requirements for the interaction with F-actin. To this end, the F-actin/PHD model of M. Lorenz et al. was employed; docking experiments of our molecular models in the PHD binding site are presented. PMID- 11757660 TI - The reaction of permanganyl chloride with olefins: intermediates and mechanism as derived from matrix-isolation studies and density functional theory calculations. AB - Density functional theory (DFT) calculations predict that the [2+3] addition of tetramethylethylene (TME) to the MnO2 moiety of MnO3Cl is thermodynamically favoured over [2+1] addition (epoxidation), while the kinetic barriers for both reactions are of comparable height. However, in an experimental investigation of the TME/MnO3Cl system by means of matrix-isolation techniques, selective formation of the epoxidation product [ClO2Mn[O[C(CH3)2]2]] (1) was observed. Compound 1 was characterised by IR spectroscopy with the aid of isotopic-enrich ment experiments in combination with DFT frequency calculations. This result, at first sight surprising, is supported by studies in solution, and, even with the numerically equal energy barriers suggested by the calculations, it can be rationalised in terms of the much broader reaction channel leading to epoxidation as opposed to the much more narrow approach path for formation of the glycolate. PMID- 11757661 TI - Complexation of triorganotin derivatives of [18]crown-6- and [15]crown-5-(benzo-4 carboxylate) with alkali thiocyanates. AB - Investigations of the simultaneous complexation of tri-n-butyltin and triphenyltin derivatives of [18]crown-6- or [15]crown-5-(benzo-4-carboxylate) by the anion and cation from NaSCN or KSCN are reported. The crystal structure of [Na+ is included in [15]crown-5-C6H3-4-COOSn(C6H5)3NCS]-], 4 NaSCN, displays an unusual zwitterionic nature with one intramolecular charge separation characterized by an Na-Sn distance of 9.29(1) A, and several intermolecular charge separations, the shortest being 5.48(1) A. Similar distances (9.70(2), 9.28(2), intramolecular; 5.40(2) and 5.41(2) A, shortest intermolecular) are observed in the more complicated structure of the corresponding [18]crown-6 (benzo-4-carboxylate) derivative, 3 NaSCN, with two independent molecules in the asymmetric unit. For the tri-n-butyltin analogues 1 and 2, complex equilibria were observed in acetone and unraveled by variable temperature 13C, 117Sn. and 23Na NMR studies. Their complexes with KSCN and NaSCN undergo decomposition in acetone solution, as evidenced by the transformation of [K+ is included in [18]crown-6-[C6H3-4-COOSn(nBu)3NCS]-], into tri-n-butyltin isothiocyanate and a novel dimeric potassium [18]crown-6-(benzo-4-carboxylate), the structure of which was elucidated by X-ray diffraction analysis. PMID- 11757662 TI - Synthesis and properties of the tetrakis(trifluoromethyl)borate anion, [b(CF3)4] : structure determination of Cs[B(CF3)4] by single-crystal X-ray diffraction. AB - Salts of the tetrakis(trifluoromethyl)borate anion, M[B(CF3)4], M=Li, K, Cs, Ag, have been prepared by two different routes for the first time. The colorless compounds are thermally stable up to 425 C (Cs salt) and soluble in anhydrous HF, water, and most organic solvents. Single crystals of Cs[B(CF3)4] were grown from diethyl ether by diffusion of CH2Cl2 vapor into the solution. The molecular structure was obtained by single-crystal X-ray diffraction. Crystal data: rhombohedral space group R3m (no. 160); a =7.883(1), c=13.847(4) A: V=748.2 A3; Z=3; T=150K; R1=0.0118, wR2=0.0290. The internal bond parameters of the [B(CF3)4] ion were compared to those of the C(CF3)4 molecule. Due to a disorder of the anions in the cesium salt, it is not possible to distinguish between T and Td symmetry by X-ray diffraction experiments alone. However, a comprehensive IR and Raman study demonstrated that in the potassium and cesium salt as well as in aqueous solution, the anion exhibits T symmetry with all CF3 groups rotated off the staggered position required for Td symmetry. The vibrational study is supported by DFT calculations, which provide, in addition to the equilibrium structure and vibrational wavenumbers, estimates of IR and Raman band intensities. The anion is resistant against strong oxidizing (e.g., F2) as well as reducing agents (e.g., Na) and is not affected by nucleophiles like C2H5O or electrophiles such as H3O+. It is very weakly coordinating, as demonstrated by the low-equilibrium CO pressure over the [Ag(CO)x][B(CF3)4] (x=1, 2) co-adducts and the formation of [Ag(CO)x][B(CF3)4] (x=3,4) at higher CO pressure. The 11B, 13C, and 19F NMR data as well as the structural parameters of the anion are compared with those for other borates containing F, CN, and CF3 ligands. PMID- 11757663 TI - Phenylene ethynylene pentamers for organic electroluminescence. AB - An isomeric family of eighteen triisopropylsilyl-capped phenylene ethynylene pentamers (molecular formula C60H62Si2) has been prepared by using fast parallel synthesis, for organic electroluminescence. Each pentamer was grown on a polymer support of propylaminomethylated polystyrene by using a series of palladium catalysed reactions between aryl iodides and alkynes. "Tea bag" technology was used to carry out several different reactions simultaneously in the same flask. Here I present the syntheses of the materials, compare their photoluminescence both in solution and in the solid state (amorphous thin films) and describe the incorporation of the most promising pentamer into organic electroluminescence devices. PMID- 11757664 TI - Conformational preferences for 3-piperideines: an Ab initio and molecular mechanics study. AB - Conformational preferences in alkyl- as well as Ph-substituted 3-piperideines (1,2,3,6-tetrahydropyridines) have been characterized by ab initio and molecular mechanics calculations. A set of rules and subrules for estimation of the conformational equilibrium (in terms of preferred substituent orientation) in these systems. with differently positioned ring substituent (-s), is presented. Examples of the revision of some previous stereochemical assignments demonstrate the reliability of these rules. PMID- 11757665 TI - 2- and 3-haloalkoxy fischer carbene complexes of chromium as synthons for either hydroxycyclopropanation or oxaspirocyclopropanation of alkenes. AB - The thermal reaction of 2-haloethoxy- and 3-chloropropoxy(alkenyl)carbene complexes of chromium with electronically neutral alkenes furnished diastereoselectively the corresponding 1-haloalkoxy-l-vinylcyclopropanes that, subjected to subsequent halogen-lithium exchange reactions, provided vinylcyclopropanols or compounds containing the spiro[cyclopropane tetrahydrofuran/tetrahydropyran] structure, depending on the nature of both the halogen atom and the lithiating reagent. The hydroxycyclopropanation reaction can be efficiently achieved in a one-pot fashion. PMID- 11757666 TI - Supramolecular solubilisation of hydrophilic dyes by using individual dendritic branches. AB - Individual dendritic branches can solubilise hydrophilic dyes in apolar media. The functional group at the focal point of the dendritic branch plays a key role in the dye uptake process. Supramolecular interactions between carboxylic acid and amine groups have been shown to be effective in enabling efficient solubilisation to occur. The necessary complementarity of this interaction is further illustrated by a series of control experiments. The extent of dendritic branching (i.e. dendritic generation) plays a key role in controlling the extent of dye uptake, with higher-generation dendritic branches exhibiting more efficient uptake at lower concentrations. UV/Visible spectroscopic methods have shown that the dendritic branches, in addition to the tuning of the extent of dye uptake, also tune the optical properties of the solubilised dye and this provides further insight into the interactions occurring between the solubilised dye and the individual dendritic branches. Furthermore, it is shown that suitably functionalised dendritic branches can transport hydrophilic dyes through an apolar phase and deliver them continuously into an aqueous medium. PMID- 11757667 TI - Heme oxygenase is the main protective enzyme in rat liver upon 6-day administration of cobalt chloride. AB - Changes in the activities of rat liver heme oxygenase (HO), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), as well as changes in lipid peroxidation and reduced glutathione (GSH) levels were measured after acute loading and chronic administration of cobalt chloride (CoCl2). Acute loading was achieved by a single subcutaneous injection of 60 mg CoCl2/kg body weight for 24 h. Chronic administration was performed by giving the same total amount of CoCl2 in small doses over longer periods of time: 30 mg CoCl2/kg daily for 2 days, 15 mg CoCl2/kg daily for 4 days, or 10 mg CoCl2/kg daily for 6 days. The results showed that HO activity was increased both after acute loading (7-fold increase) and upon 6-day administration of CoCl2 (5-fold increase). The GSH level, 24 h after a single injection of CoCl2, was lower than that of the control animals. However, upon chronic administration of small doses CoCl2, the level of GSH increased and was accompanied by an increase in GR activity. Chronic administration of CoCl2 produced persistent oxidative stress, which was illustrated with a continuous increase in lipid peroxidation. At the same time, under these conditions, the activities of oxidative-stress-protective enzymes were either inhibited (SOD, catalase) or not significantly changed (GPx). Collectively, these findings suggest that the sustained up-regulation of HO activity in rat liver upon 6 day administration of CoCl2 would be beneficial by providing the cells with antioxidants, biliverdin and bilirubin, and together with the increased levels of GSH would act as a part of the defence mechanisms against the cobalt-induced oxidative stress. PMID- 11757668 TI - Effect of cold hypoxic storage and reoxygenation at 37 degrees C of cultured precision-cut rat liver slices on paracetamol metabolism. AB - The influence of cold storage and reoxygenation at 37 degrees C of precision-cut rat liver slices on paracetamol metabolism was studied. A depressed metabolism was observed after cold preservation, but during reoxygenation at 37 degrees C slices were capable of synthesizing proteins and maintaining both glutathione and ATP levels. Recovery was faster in slices under aerobic cold conditions than in those under cold hypoxia. Glycogen levels were dramatically decreased under both conditions and subsequent reoxygenation at 37 degrees C still increased the glycogenolysis. Xenobiotic metabolism after reoxygenation of cold-preserved slices shows that glucuronide and sulfate conjugates of paracetamol represent about 50% of those of fresh slices at zero time. The amounts of phase II apoproteins were virtually unchanged, thus suggesting that loss of enzyme activities are most probably due to lack of cofactors. Reoxygenation at 37 degrees C did not impair cell metabolism, and a potential role for nitric oxide and other cytokines released form Kupffer cells appears unlikely since nitrite was not formed after bacterial endotoxin stimulation. The maintenance of energetic stores during cold preservation appears, therefore, to be a critical issue for the survival and metabolic activity of cells. PMID- 11757669 TI - Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and bladder cancer susceptibility in the Turkish population. AB - We investigated the effect of the GSTM1 and GSTT1 null genotypes, and GSTP1 313 A/G polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients, and 121 age- and sex-matched controls of the Turkish population. The adjusted odds ratio for age, sex, and smoking status is 1.94 [95% confidence intervals (CI) 1.15-3.26] for the GSTM1 null genotype, and 1.75 (95% CT 1.03-2.99) for the GSTP1 313 A/G or G/G genotypes. GSTT1 was shown not to be associated with bladder cancer. Combination of the two high-risk genotypes. GSTM1 null and GSTP1 313 A/G or G/G, revealed that the risk increases to 3.91-fold (95% CI 1.88-8.13) compared with the combination of the low-risk genotypes of these loci. In individuals with the combined risk factors of cigarette smoking and the GSTM1 null genotype, the risk of bladder cancer is 2.81 times (95% CI 1.23-6.35) that of persons who both carry the GSTM1-present genotype and do not smoke. Similarly, the risk is 2.38-fold (95% CI 1.12-4.95) for the combined GSTP1 313 A/G and G/ G genotypes and smoking. These findings support the role for the GSTM1 null and the GSTP1 313 AG or GG genotypes in the development of bladder cancer. Furthermore, gene-gene (GSTM1-GSTP1) and gene-environment (GSTM1-smoking, GSTP1 smoking) interactions increase this risk substantially. PMID- 11757670 TI - Hydrogen peroxide production in mouse tissues after acute d-amphetamine administration. Influence of monoamine oxidase inhibition. AB - The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (H2O2) by metabolic or non-metabolic redox pathways, the main objective of this work was to evaluate d-amphetamine-induced H2O2 production in mice liver, kidney and heart. The contribution of monoamine oxidase (MAO) to H2O2 production after d-amphetamine administration was studied using the MAO inhibitor pargyline. H2O2 production was measured indirectly using the catalase-H2O2 complex I irreversible inhibitor 3-amino-1,2,4-triazole (AT). Using this method, the measurement of residual catalase activity following administration of AT permits the monitoring of H2O2 production in vivo. Charles River CD-1 mice (30-35 g body weight) were injected with AT just before the injection of d-amphetamine sulphate (20 mg/kg). d-Amphetamine stimulated the production of H2O2 in all tissues studied, although to different degrees. MAO inhibition by itself led to a remarkable decrease of basal H2O2 production in the kidney and a slight decrease in the liver, although no effect was observed in the heart. d-Amphetamine-induced H2O2 production in the heart and kidney was reduced in MAO-inhibited mice. However, in the liver, H2O2 production was transiently potentiated at 30 min under MAO inhibition. In conclusion, d-amphetamine administration leads to an increase in H2O2 production in mouse liver, kidney and heart, and monoamine oxidase plays an important role in this effect. PMID- 11757671 TI - Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen. AB - We have investigated the cytokine response pattern following sensitisation (induction) of BALB/c mice with different chemicals (dinitrochlorobenzene, dinitrofluorobenzene, oxazolone, glutaraldehyde, formaldehyde, trimellitic anhydride, croton oil) and elicitation (challenge) of contact allergy in sensitised animals. The results of our investigations showed that different chemicals induced both T helper (Th) 1 cytokines [interleukin (IL) 2, interferon beta (IFNgamma) [corrected] and Th2 cytokines (IL-4, IL-10) at different stages during murine contact allergy. We also confirmed our previous findings that IL-4 and IL-10 release were up-regulated during the challenge phase regardless the contact allergen used, whereas the release of IFNgamma [corrected] did not show a clear preference for being up- or down-regulated. In our hands, the increased expression of Th2 cytokines after challenge exposure to contact allergens appeared as a stable marker of secondary contact allergenic responses. Quantitative differences in the expression of IL-4 were observed between different contact allergens. The present results clearly indicate that skin sensitisers were able to elicit cytokine response patterns, which could not be related to a clear-cut Th1 or Th2 type of cytokine response. Furthermore, dermal application of contact allergens produced different kinetics of cytokine secretion upon induction and challenge. In our hands, the co-expression of Th1 and Th2 type cytokines appeared as a universal consequence of dermal application of contact allergens to responsive mice. Our results indicate that co-expression of Th1 and Th2 cytokines during contact allergy is an important feature of murine contact allergy in responsive mice and that chemicals differ in their potency to induce the expression of these cytokines. Furthermore, the results do not support the view that different chemicals induce Th1 or Th2 cytokines in a mutually exclusive manner depending on their preference for inducing either contact or respiratory allergy. The results are expected to renew the discussion about the usefulness of the Th1/Th2 paradigm in certain areas of immunotoxicology. PMID- 11757672 TI - Effects of sub-chronic in vivo chlorpyrifos exposure on muscarinic receptors and adenylate cyclase of rat striatum. AB - In this study dosing regimens were designed such that cholinesterase inhibition following exposure to chlorpyrifos was produced in one treatment group, but was absent in the other. The higher dosing regimen inhibited plasma and brain cholinesterase activities by 51 and 70%, respectively, and resulted in decreased [3H]cis-methyldioxolane ([3H]CD) binding, which was attributable to a decrease in Bmax. No concomitant loss of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites was observed, indicating that the M2 muscarinic receptor subtype to which [3H]CD binds is particularly susceptible to alterations induced by chlorpyrifos treatment. As the M2 receptor subtype is surmised to be the muscarinic autoreceptor, decreases in this receptor may exacerbate poisoning by organophosphorus agents as a result of decreased ability to terminate synaptic acetylcholine release. The ability of carbachol to inhibit striatal adenylate cyclase, which is an effector molecule associated with the M2 receptor, was unaltered in chlorpyrifos-treated rats. Decreases in M2 receptors occurred with the higher dosing regimen, in the absence of any clinical manifestations. Thus, in the absence of overt clinical signs, perturbations of the muscarinic receptor system did occur as a result of sub-chronic chlorpyrifos exposure. Such alterations may contribute to neurological impairments that develop following chronic organophosphorus exposure. PMID- 11757673 TI - Adenine nucleotide and calpain inhibitor I protect against atractyloside-induced toxicity in rat renal cortical slices in vitro. AB - Atractyloside is a compound with a documented nephrotoxicity. It induces renal tubular necrosis at high doses and apoptosis at lower doses. This study investigates the potential protective effect of some chemical agents against atractyloside-induced nephrotoxicity in vitro using the precision-cut rat renal cortical slices obtained from kidneys of Wistar rats. For co-incubation experiments, slices were incubated for 3 h at 37 degrees C on a rocker platform with various chemical agents: ADP (5 mM), calpain inhibitor I (CPI, 1 mM), stevioside (STV, 2.5 mM) or probenecid (PRB, 2.5 mM) in the presence or absence of atractyloside (2 mM). For pre-incubation experiments, slices were incubated with the same chemical agents for 1 h before exposure to atractyloside. The nephrotoxic effects of atractyloside (2 mM) alone were manifested in several ways: by a marked increase in lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) leakage, significant inhibition of p-aminohippurate (PAH) accumulation, marked depletion of intracellular ATP and reduced glutathione (GSH), and a significant reduction in pyruvate-stimulated gluconeogenesis. Co incubation of slices with ADP or CPI and atractyloside completely blocked atractyloside-induced increase in LDH leakage, but not ALP leakage. Atractyloside induced depletion of ATP and reduced gluconeogenesis was prevented by co incubation with ADP or CPI. Furthermore, co-incubation of slices with STV and atractyloside, but not PRB, completely abolished atractyloside-induced depletion of ATP and decreased gluconeogenesis in the slices. Pre-incubation of slices with either ADP or CPI protected against atractyloside-induced increase in LDH leakage, reduced ATP and decreased gluconeogenesis. PAH uptake in the slices was inhibited by atractyloside and PRB in a time-dependent manner. While ADP and CPI were found to exert complete protection against atractyloside-induced toxicity irrespective of treatment schedule, STV is effective only under certain conditions, and PRB offer no protection at all. The results of this study demonstrate the usefulness of renal cortical slices as toxicology tool for evaluating and screening compounds for their potential protective effects, and are supportive of a role of adeninine nucleotide (ADP) and protease inhibitor (CPI) in protecting against atractyloside-induced cell injury. PMID- 11757674 TI - Effects of all-trans-retinoic acid and all-trans-retinoyl glucuronide in two in vitro systems of distinct biological complexity. AB - In vitro systems are widely used to evaluate the embryotoxic potential of retinoids. The effective concentrations of these retinoids, however, are not consistent in the various in vitro systems used in evaluating embryotoxicity. This may be explained by the different level of complexity for each individual system, which may lead to different concentrations of the substances in the target tissues. To verify this hypothesis we have compared two in vitro systems of distinct biological complexity: the rat whole embryo culture system, and the mouse limb bud organ culture system. The lipid soluble, teratogenic retinoid all trans-retinoic acid (ATRA), and all-trans-retinoyl-beta-D-glucuronide (ATRAG), an endogenous, water-soluble and biologically active retinoid with limited placental transfer, were compared with regard to their embryotoxic potential in vitro. In both in vitro systems, ATRAG showed a lower degree of embryotoxicity than ATRA. In the limb bud organ culture, ATRAG revealed only slightly less toxicity than ATRA, whereas the effective concentrations of the two compounds in the whole embryo culture system differed by almost two orders of magnitude. During incubation with ATRAG, ATRA is generated by hydrolysis and is found in culture media and exposed tissues. The presence of membrane barriers around the developing embryo in the whole embryo culture system possibly prevents the transfer of ATRAG to the embryo and, therefore, its exposure to the active hydrolysis product ATRA. From these results we conclude that analysis of retinoid concentrations in the culture media and in the exposed tissues is essential for the interpretation of results obtained from in vitro toxicity testing. PMID- 11757675 TI - Diagnostic imaging and clinical findings in rhombencephalosynapsis: case report and literature review. AB - Rhombencephalosynapsis is a rare condition in which most cases are found in newborns and infants. Morphological findings are predominantly characterized by fusion of the cerebellar hemispheres and absence of the vermis with often associated supratentorial anomalies. We review the literature with emphasis on diagnostic imaging of this condition and present a case of a 2-year-old girl. PMID- 11757676 TI - Inflammatory pseudopolyposis in a patient with toxic megacolon due to pseudomembranous colitis. PMID- 11757677 TI - Gamna-Gandy bodies. PMID- 11757678 TI - Since 1895, orthopaedic surgery needs X-ray imaging: a historical overview from discovery to computed tomography. AB - The first application of X-ray techniques to human beings was made in Germany by Wilhelm Conrad Rontgen in November 1895. From this first use, different groups became interested in creating and improving the technical devices. Focusing on Germany, in honour of the centenary of the awarding of the first Nobel Prize in Physics to Rontgen in 1901, we present some of the milestones in X-ray imaging, from the first pioneer's approach on glass plates, cathode X-ray tubes, fluoroscopy, earlier communications leading to X-ray films and screens, rotating xray tubes, tomography and CT, classic textbooks, radioprotection aspects, as well as some contributions in radiological techniques and orthopedic pathology. PMID- 11757679 TI - Were X-rays produced before the discovery by Rontgen? AB - Were X-rays produced before their formal discovery by Rontgen? Analysis of unexpected findings by others shows that undoubtedly X-rays were produced before Rontgen. However, the latter is the real discoverer of the rays named by himself "X-rays" or Rontgen rays to honour his discovery so meaningful for the patients all over the world in the diagnosis and treatment of severe illnesses as cancer, and also used in some industrial applications. PMID- 11757680 TI - Functional methods for quantifying agonists and antagonists. AB - The development of occupancy theory has allowed the formulation of a series of mathematical models that describe the interaction of agonists and antagonists with their receptors, in terms of affinity and efficacy. These models provide a framework for the analysis and interpretation of E/[A] curve data and have proved to be useful tools in quantitative pharmacology. Unfortunately, despite the proven utility of this approach and the widespread availability of powerful computer-based curve-fitting programs [BMDP (41), Microsoft Excel. etc.], which greatly facilitate analysis, the application of mathematical modeling remains the exception rather than the rule in pharmacological studies. PMID- 11757681 TI - Quantification of receptor interactions using binding methods. PMID- 11757683 TI - The use of electrophysiology to improve understanding of drug-receptor interactions. PMID- 11757682 TI - Drug analysis based on signaling responses to G-protein-coupled receptors. PMID- 11757684 TI - Lipid-based formulations for oral administration: opportunities for bioavailability enhancement and lipoprotein targeting of lipophilic drugs. PMID- 11757685 TI - Topical application of drugs: mechanisms involved in chemical enhancement. PMID- 11757686 TI - Drug targeting by retrometabolic design: soft drugs and chemical delivery systems. PMID- 11757687 TI - Lymphoma 2000. The First International Symposium on Biology and Treatment of Aggressive Lymphomas: The stagnation seems to be over. PMID- 11757688 TI - MALT lymphomas: a radiation oncology viewpoint. PMID- 11757689 TI - Helicobacter pylori eradication therapy in gastric high grade non Hodgkin's lymphoma (NHL). AB - BACKGROUND: Primary gastric low-grade lymphoma of the mucosa associated lymphoid tissue (MALT) develops on the background of a chronic Helicobacter pylori (H. pylori) infection. Stable remissions can be induced by H. pylori eradication therapy as shown in clinical trials. In 8 cases of high-grade gastric lymphomas remissions after H. pylori eradication were observed retrospectively. AIM: We started a pilot-trial to investigate the value of H. pylori eradication therapy in early gastric high-grade B-cell lymphoma prospectively. PATIENTS AND METHODS: So far, two H. pylori positive patients with high-grade B-cell lymphoma of the stomach stage Ann Arbor I E are included. They received a triple eradication therapy (Clarithromycin 500 mg/d, Metronidazol 800 mg/d and Omeprazol 40 mg/d) for 7 days. Endoscopic controls are preformed every 4 weeks. RESULTS: Both patients became H. pylori negative after eradication therapy. One patient achieved complete remission (CR) 38 days after eradication. The continuous complete remission lasts now for 170 days. The second patient received only a partial remission (PR) 4 weeks after eradication and showed a slight progress 4 weeks later. He presently receives chemotherapy (CHOP). CONCLUSIONS: Patients with early high-grade gastric B-cell lymphomas should receive H. pylori eradication only within clinical trials. It seems to be possible to induce remissions of early high-grade gastric B-cell lymphomas with exclusive H. pylori eradication therapy. The stability of remission remains to be unclear and should be evaluated by following up the patients closely. PMID- 11757690 TI - Therapy of PCNSL at the Massachusetts General Hospital with high dose methotrexate and deferred radiotherapy. PMID- 11757691 TI - Therapeutic management of refractory or relapsed primary central nervous system lymphomas. AB - Despite the high rate of complete remission achieved with first-line therapy, 10 15% of immunocompetent PCNSL patients are treatment refractory while 35-60% relapse and die of lymphoma within a few months. In many cases, salvage therapy produces a second complete remission with consequent symptomatic and survival improvement. Due to the heterogeneity of both first and second line therapies employed, the optimal schedule for salvage therapy can not be identified. Nevertheless, some therapeutic guidelines could be suggested. Radiotherapy is an effective option for both previously irradiated and radiotherapy naive patients. Some authors have been able to minimize the incidence of actinic toxicity by using chemotherapy alone at failure. In patients that have relapsed after receiving high-dose methotrexate (HD-MTX), the same drug again has been successfully employed while HD-cytarabine has been the most widely used cytostatic. Ocular recurrence can be treated with cytarabine or focal radiotherapy. Meningeal relapse can be treated with spinal cord irradiation, intrathecal and/or systemic chemotherapy. Salvage therapy, beyond improving survival, constitutes the selection ground for testing active agents. The addition of other cytostatics to HD-MTX has been empirically based and without a clear survival benefit, but with a higher toxicity. Intriguing preliminary results from small pilot studies are now available with topotecan, rituximab, temozolomide, PCV regimen and HD-chemotherapy supported by autologous or allogeneic peripheral blood stem cells transplantation. Considering its positive effect on survival and the potential improvement in neurological symptoms and quality of life, salvage therapy seems to be a valuable treatment in PCNSL patients. Finally, the inclusion of relapsing or progressive PCNSL patients into second-line prospective clinical trials for testing therapeutic agents should be strongly encouraged. PMID- 11757692 TI - Indications for early autologous stem cell transplantation in aggressive lymphoma. PMID- 11757694 TI - The future of monoclonal antibody engineering. PMID- 11757693 TI - High-dose sequential (HDS) chemotherapy for high-risk non-Hodgkin's lymphoma: long-term analysis and future developments. PMID- 11757695 TI - 3. Report on workshop: UICC workshop "Therapy of NHL in early stages". Part 1: Follicular lymphoma. PMID- 11757696 TI - High dose radioimmunotherapy in relapsed B-cell lymphoma with I-131 rituximab. PMID- 11757697 TI - New strategies for vaccination and imunomodulation in NHL. AB - Knowledge of the genetic changes which occur in cancer cells is stimulating research aimed towards new therapies. Immunotherapeutic approaches, particularly antibody therapy, are already finding a place in treatment of hematological malignancies. Vaccination will build on experience in the field of infectious diseases, and it should be possible to design vehicles to deliver the expanding range of tumour antigens to the immune system. For DNA vaccines, fusion genes have the potential to activate and direct immune effector pathways. One candidate antigen for B-cell malignancies is the clonal idiotypic immunoglobulin and we have designed a fusion vaccine encoding idiotypic sequence fused to a sequence from a powerful antigen from tetanus toxin. This promotes protective immunity against lymphoma in models, and is now in clinical trial. One challenge is to bring patients into remission without significant damage to immune capacity. Another is to rethink the nature of clinical trials so that more pilot studies of efficacy can be carried out. There is no evidence so far of toxicity due to injection of DNA, but for antigens which are expressed by normal cells, the line between attack on tumour and autoimmunity will have to be carefully drawn. PMID- 11757698 TI - 4. Report on workshop: UICC workshop "Therapy of NHL in early stages". Part 2: Aggressive lymphomas. PMID- 11757699 TI - 5. Report on workshop: Primary CNS lymphoma. AB - The increase in primary CNS lymphoma (PCNSL) has resulted in a growing interest in this disease. Despite efforts to optimize the management of PCNSL, several therapeutic questions remain unanswered. Due to methodological pitfalls in the clinical trials published thus far, particulary their uni- or oligocenter setting and the small number of patients, it has been difficult to draw definitive conclusions. Future efforts should concentrate on identifying optimal chemotherapy combinations, evaluating the efficacy of modern therapy options such as high-dose chemotherapy supported by autologous blood stem cell transplantation, and clarifying the impact of radiotherapy delay in complete responders to chemotherapy. Standardized neuropsychological testing and quality of-life assessment are indispensable in future PCNSL trials. Important questions regarding management of PCNSL should be preferably addressed in large multicenter prospective randomized trials. PMID- 11757700 TI - 6. Report on workshop: EBMT workshop "High dose therapy in aggressive NHL". PMID- 11757701 TI - Cell death in T- and B-cell development. PMID- 11757702 TI - Cytogenetic subtyping of diffuse large B-cell lymphomas. PMID- 11757703 TI - Potential of chromosomal and matrix-based comparative genomic hybridization for molecular diagnostics in lymphomas. PMID- 11757704 TI - Gene expression analysis in aggressive NHL. AB - The mRNA expression profile of a tumor reflects the unique genetic alterations present and is predictive of the clinical and biological characteristics of the tumor. Novel techniques have been developed to determine the global gene expression pattern of normal and neoplastic tissues. A cDNA microarray uniquely suitable for the analysis of B-cell non-Hodgkin's lymphomas (B-NHL) has been developed and preliminary analysis on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and B-chronic lymphocytic leukemia (CLL) has been performed. These studies indicate that: 1) it is feasible to determine the gene expression profiles of archival lymphoma samples frozen and stored in a clinical setting, 2) the expression profile of these 3 types of lymphoproliferative disorders are distinctive, 3) DLBCL can be divided into at least 2 major subgroups according to their pattern of expression of B-cell associated genes and 4) the gene expression patterns in DLBCL appear to have prognostic significance. A larger study of DLBCL is currently underway to confirm and extend our findings. Gene expression profiles will be correlated with cytogenetic and clinical data to identify distinctive profiles that are of clinical and biological significance and to delineate key genetic lesions that determine these profiles. The new information will allow the design of a simpler and less expensive array for clinical use. The diagnostic array could provide rapid molecular characterization of every B-NHL at presentation for optimal treatment decisions and prognostication. It is anticipated that this project will advance our understanding of the molecular mechanisms in the neoplastic transformation of B lymphoid cells and the new insights will help to identify promising molecular targets for therapeutic intervention. PMID- 11757705 TI - Prognostic factors in aggressive lymphoma: the contribution of novel biological markers. PMID- 11757706 TI - Therapeutic consequences of pathology and prognostic factors in aggressive NHL- analysis of ALCL. PMID- 11757707 TI - Mediastinal B-cell lymphoma, a lymphoma type with several characteristics unique among diffuse large B-cell lymphomas. AB - Mediastinal B-cell lymphoma is a locally highly aggressive tumor with a rather unique pattern of clinical, morphologic, imunologic, and genetic features distinct from other diffuse large B-cell lymphomas. Characterization of this disease has been hampered by the relatively low incidence of this lymphoma type. Although recent studies on larger numbers of cases have allowed new insights into biology and clinics of this lymphoma type, the histogenesis of mediastinal B-cell lymphoma is not yet fully understood. This review will list morphologic, immunlogic, and genetic properties of mediastinal B-cell lymphoma and discuss recent data regarding the biology of this lymphoma type. PMID- 11757708 TI - Workshop report: "Genetics and immunology of aggressive NHL". PMID- 11757709 TI - Novel imaging techniques in NHL: clinical results with PET imaging. PMID- 11757710 TI - Five theses concerning the clinical consequences of pathology and prognostic factors. AB - We discuss possible justifications to split study populations from a biometrical point of view. The existence of prognostic differences between subgroups are neither a sufficient nor a necessary reason to justify a splitting decision. There are essentially two separate types of relevant arguments to justify a split of patient study populations: a) Different toxicity/benefit trade-offs concerning the acceptability of a particularly aggressive treatment, b) Evidence for strong treatment by subgroup interactions, i.e. Treatment differences differ markedly by biologically defined subgroups. The latter is what the research ideal of biologically specific treatment asks for. Subgroup analysis is notoriously difficult. Formal statistical analysis must be complemented by specific evidence from basic sciences. Meta-subgroup analyses may be an option if a biologically specific hypothesis on which treatment component interacts with what biological feature allows to operationally identify all those randomised trials in which the effect should be present. In this conceptual and methodological paper we defend five theses concerning the clinical consequences of pathological and biological differences from a somewhat unorthodox biometrical point of view. PMID- 11757711 TI - Follicular non-Hodgkin's lymphoma: the role of radiation therapy. PMID- 11757712 TI - Management of localized (stage I and II) clinically aggressive lymphomas. AB - The treatment for non-Hodgkin's lymphomas is chiefly dependent on the histologic type and the anatomic extent of the disease, reflected by the stage. In the past 30 years, the treatment of localized large cell lymphomas has evolved from the use of radiotherapy (RT) alone to the routine use of combined modality therapy (CMT). Randomized controlled trials have shown superiority of the CMT approach as compared to RT alone, or chemotherapy alone. The data will be critically appraised in this review. Currently, approximately two-thirds of patients with stage I and II clinically-aggressive lymphomas will be cured with initial planned combined modality therapy. The clinical prognostic factors predicting refractory or relapse disease are now clearly recognized, and they are: older age, stage II disease, high lactate dehydrogenase (LDH), poor performance status, and bulky disease. Patients with poor-risk features are candidates for clinical trials to examine the potential benefits of initial treatment intensification programs. Elderly patients over the age of 60 years account for about half of the patients with lymphoma, and they may tolerate therapy less well. They are a special subgroup where prospective studies are required to determine the optimal management. PMID- 11757713 TI - Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy. AB - In study NHL-BFM 90 we investigated the efficacy of an ALL-type treatment without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). In particular, the prognostic impact of the speed of tumor regression was evaluated. From April 1990 to March 1995, 105 evaluable patients, 1.1-16.4 years of age, with T-LBL were enrolled into study NHL-BFM 90. Patients with stage I and II received an 8-drug induction followed by a consolidation including high-dose methotrexate (MTX) and maintenance therapy up to a total therapy duration of 24 months. Patients with stage III and IV received an additional reinduction and cranial radiotherapy (CRT) (12 Gy for prophylaxis) between consolidation and maintenance. Residual tumor after completion of induction had to be resected. No local RT was applied. Patients received intensified chemotherapy if tumor regression on day 33 of induction was <70% or when vital residual tumor was present after the induction phase. With a median follow-up of 6.41 years, pEFS at 5 years is 91.4% (SE+/-2.7%). 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to <70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. Our data demonstrate that, with intensive ALL-type chemotherapy but no local radiotherapy, an event free survival rate of 90% can be achieved in childhood T-LBL. Providing tumor regression within 5 weeks is sufficient, tumor remnants after induction have weak prognostic impact. PMID- 11757715 TI - 2. Report on the workshop: "Clinical consequences of pathology and prognostic factors in aggressive NHL". PMID- 11757714 TI - Therapeutic strategies for aggressive lymphomas: the trials of the DSHNHL. PMID- 11757716 TI - Consolidation radiotherapy to bulky disease in aggressive NHL. First results of the NHL B-94 trial of the DSHNHL. AB - The impact of radiotherapy in aggressive NHL is not well defined. In the NHL B-94 trial of the DSHNHL, an irradiation of bulky disease areas was done after completing 6 cycles of CHOP/CHOEP chemotherapy. In the entire patient group, including those patients with extranodal disease and those who did not receive the complete chemotherapy, bulky disease was a significant independent prognostic factor concerning recurrence-free survival (66.1% (no bulk) vs. 53.3% (bulk), p=0.0001). Out of 366 patients with nodal disease only and 6 cycles of chemotherapy according to the protocol, 84 of 91 patients with bulky disease were irradiated with 36 Gy. In this group of patients the prognostic impact of bulky disease could not be shown any longer (recurrence-free survival 77.3% (no bulk) vs. 74.1% (bulk). Localized radiotherapy of bulky disease areas may therefore have contributed to an improvement in outcome in this high-risk group. PMID- 11757717 TI - Treatment strategies in elderly patients with aggressive histology lymphoma. PMID- 11757718 TI - Modelling of chemotherapy: the effective dose approach. AB - We sketch the development of the effective dose approach which provides a theoretical framework to interpret chemotherapy outcome data. Building on the generalised Skipper model of chemotherapy, a meta-regression method is derived to jointly analyse all chemotherapy comparing randomised clinical trials in a given malignancy in order to explore the slope of the effective dose/outcome relationship and the relative potency of cytostatic drugs. The model is applied to explain why treatment differences in aggressive NHL appear to differ by risk groups in aggressive NHL. A respective meta-subgroup analysis to confirm this interaction hypothesis is proposed. PMID- 11757719 TI - Radiotherapy in early stage gastrointestinal lymphoma: results of the German GIT NHL group. PMID- 11757720 TI - The beta-globin genotype E121Q/W15X (cd121GAA-->CAA/cd15TGG-->TGA) underlines Hb d/beta-(0) thalassaemia marked by domination of haemoglobin D. AB - Among 13,525 haemoglobin analyses performed in our laboratory we detected 21 cases of haemoglobin D (Hb D) disease. Investigation of a family affected with this abnormal haemoglobin revealed two cases of Hb D/beta-(0) thalassaemia for the first time among Saudi Arabs. The two patients were diagnosed as having chronic haemolytic anaemia of moderate severity on the basis of the haemoglobin level, haematocrit, mean corpuscular haemoglobin, mean corpuscular volume, reticulocyte count, red blood cell count microscopy, elevated serum conjugated and non-conjugated bilirubin, increased serum lactic dehydrogenase, and the occasional need for blood transfusions. Genetic analysis enabled the detection of compound heterozygosity for the missense E121Q (codon 121 GAA-->CAA) and stop W15X (codon 15 TGG-->TGA) mutations as causative of the clinical phenotype of Hb D-LosAngeles (Punjab)/beta-(0) thalassaemia. The disease manifested as domination of Hb D and moderate haemolytic anaemia. The co-inheritance of beta-(0) thalassaemia seems to be responsible for conferring the deleterious effect on the presentation of Hb D disease in these patients. The present result emphasizes the significance of molecular testing in resolving certain diagnostic ambiguities in haematology as in cases of heterozygous Hb D in association with beta-(0) thalassaemia which, by haemoglobin electrophoresis, may be misdiagnosed as Hb D homozygosity. PMID- 11757721 TI - Immunosuppressive therapy for patients with refractory anemia. AB - Trials of immunosuppressive therapy have been reported in some case reports of hypoplastic myelodysplastic syndrome (MDS). In this study, we gave immunosuppressive therapies to eight patients with normo- or hyperplastic MDS of refractory anemia subtype without karyotypic abnormalities and analyzed the HLA DRB1 type or the presence of paroxysmal nocturnal hemoglobinuria (PNH) neutrophils in these patients. Cyclosporin A (CyA) therapy was effective for improving cytopenia in four of the eight MDS patients. While the side effects of CyA were mostly mild and transient, one patient demonstrated karyotypic abnormality following CyA therapy and accelerated to refractory anemia with an excess of blasts. Additional antithymocyte globulin (ATG) therapy was effective in one of three nonresponders to CyA therapy. One patient died due to leukemic transformation after ATG therapy. When we analyzed the correlation between the response to CyA therapy and the HLA-DRB1 type, there were more responders with DRB1*1501 (three of four patients) than without (one of four patients), but a statistically significant difference was not evident between the two groups. In addition, the presence of PNH neutrophils was not correlated with the response to CyA and/or ATG therapy. These results indicate the usefulness of immunosuppressive therapies even for normo- or hyperplastic MDS patients. Further trials using more patients with a long follow-up period would be worthwhile in order to clarify the possibility of disease progression and in order to predict the response of patients. PMID- 11757722 TI - Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses. AB - CD34+ cell counts in peripheral blood (PB) and corresponding numbers of CD34+ cells and colony-forming units-granulocyte/macrophage (CFU-GM) in 299 leukapheresis products of 209 patients undergoing PB progenitor cell (PBPC) mobilization for autologous transplantation in two different centers were analyzed and compared according to diagnosis: non-Hodgkin lymphoma (NHL, 94 leukaphereses), multiple myeloma (MM, 75), Hodgkin's disease (HD, 37), solid tumors (35), and chronic myeloid leukemia (CML, 32). Without separating disease entities, correlations between PB CD34+ cell counts and leukapheresis content of CD34+ cells (r>0.83, P<0.01) and CFU-GM (r>0.81, P<0.01) were excellent. In both centers, a PB CD34 threshold ensuring a leukapheresis yield > 10(6) CD34/kg was determined. This threshold was higher in center 1 than in center 2, and its predictive accuracy (91.4%, i.e., prediction correct 91.4% of the time) was significantly lower than in center 2 (98.4%, P=0.02). When data were analyzed by pathology, PB CD34+ cell counts and leukapheresis content of CD34+ cells and CFU GM remained well correlated, and in both centers PB CD34 thresholds predictive of a yield > 10(6) CD34/kg per leukapheresis could be determined for each pathology. For most patients, pathology-specific PB CD34 thresholds could be obtained directly from the equation of the PB CD34/leukapheresis CD34 correlation curve; they varied depending on both pathology and center (range: 7-20 x 10(6) CD34/l). Pathology-specific thresholds predicted a leukapheresis yield > or = 10(6) CD34/kg accurately 100% of the time for MM patients in center 2 and HD and solid tumor patients of both centers, resulting in overall rates of accurate prediction of sufficient graft CD34 content of 96.6% in center 1 and 98.9% in center 2. PMID- 11757723 TI - Adult lymphoblastic lymphoma in Taiwan: an analysis of treatment results of 26 patients. AB - Lymphoblastic lymphoma (LBL) frequently affects young adults and usually presents with a mediastinal mass as well as bone marrow involvement. Although the frequency of LBL in the Far East is higher than that of Western countries, no reports regarding treatment of this disease have as yet been reported. We herein report our treatment experience and verify the efficacy of the Stanford/Northern California Oncology Group (NCOG) protocol for this disease and recommend treatment strategies for LBL patients. We retrospectively reviewed the medical records of adult LBL patients treated in our hospital from 1986 to 1996. Twenty seven patients were diagnosed to have LBL. These patients' ages ranged from 17 to 73 years old with a median of 23. Nineteen patients had an initial stage IV disease. Of the 23 cases in which immunological studies were performed, 20 proved to be of T cell lineage, 1 of B cell type, and the other 2 lacked both T and B markers. Three major chemotherapeutic regimens including prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide-mechlorethamine, vincristine, procarbazine, prednisone (ProMACE-MOPP), cyclophosphamide, hydroxydaunomycin, vincristine, prednisone (CHOP), and the Stanford/NCOG protocol were used to treat 3, 6, and 15 patients, respectively. Two other patients were treated with two different chemotherapeutic regimens, respectively. One patient was excluded for analysis because of initial treatment by surgery. The complete response (CR) rates with ProMACE-MOPP, CHOP, and the Stanford/NCOG regimens were 0%, 17%, 80% and median overall survival 9, 8.5, and 15 months, respectively. Five patients with stage II-III diseases achieved long-term disease-free survival of 11-36 months with the Stanford/NCOG protocol with a median follow-up of 24 months. Four patients in late stage or relapse received allogeneic bone marrow transplantation (BMT). Two of them obtained long-term disease-free survival. Two other patients in CR were treated with high-dose chemotherapy (HDCT) supported with autologous BMT and peripheral blood stem cell transplantation (PBSCT), respectively. The patient receiving HDCT with autologous PBSCT died of LBL relapse 6 months after transplantation. The other patient undergoing HDCT with autologous BMT died of fulminant hepatitis 5.5 months after transplantation. The median overall survival of all these 26 patients was 12 months. B symptoms and treatment without the Stanford/NCOG protocol were found to have significantly negative impacts on both patients' overall and progression-free survivals. Our results suggest that the Stanford/NCOG protocol may be an effective chemotherapy for adult LBL and may provide long-term remission for patients in an early stage of disease. For those patients with LBL in an advanced stage or in relapse, HDCT with allogeneic or autologous BMT is probably the treatment of choice. PMID- 11757724 TI - Assessment of clonality of rosetting T lymphocytes in Hodgkin's disease by single cell polymerase chain reaction: detection of clonality in a polyclonal background in a case of lymphocyte predominance Hodgkin's disease. AB - Rosetting of CD4+ T cells around the neoplastic Hodgkin and Reed-Sternberg (H&RS) cells is a characteristic feature of Hodgkin's disease (HD). To answer the question whether this phenomenon is solely due to chemokine-mediated attraction of T cells or whether the rosetting T cells in addition recognize antigens presented by the H&RS cells, we examined the T cells adherent to H&RS cells. Cells from five cases of HD [four classic HD and one lymphocyte-predominant (LP) HD] were examined by single-cell analysis for the T-cell receptor (TCR) gamma gene. Between 5 and 17 rosettes containing one to ten rosetting lymphocytes and the corresponding H&RS cells were amplified in separate plastic tubes. Of the resulting 119 TCRgamma polymerase chain reaction (PCR) products, 87 were sequenced. While no evidence of a clonal expansion was obtained in the lymph nodes from four of five patients with classic HD, clonal TCRgamma sequences were found in the lymph node from the patient within LPHD in two independent experiments analyzing seven and ten different rosetting complexes, respectively. Of 13 products, 11 showed identical Vgamma9 sequences. Unrelated products were found in all other TCRgamma family subgroups in this case. Single H&RS cells picked as controls were negative for TCRgamma rearrangements. Our results demonstrate that clonal proliferations on a polyclonal background can occur among the T cells forming rosettes with Hodgkin cells and lend support to the view that Hodgkin cells may also function as cells presenting antigens to the adhering T cells. PMID- 11757725 TI - New insights into the biology of multiple myeloma using a combination of May Grunwald-Giemsa staining and fluorescence in situ hybridization techniques at the single cell level. AB - Up to now only limited information is available about the significance of chromosomal aberrations in multiple myeloma (MM) and about the time point of the neoplastic transformation. Fluorescence in situ hybridization (FISH) combined with standard May-Grunwald-Giemsa (MGG) staining or immunophenotyping on a single cell level were applied. Bone marrow (BM) samples were obtained from 11 patients with morphologically proven multiple myeloma. For detection of the chromosomal aberrations, we used FISH on interphase nuclei with commercially available centromere-specific probes for chromosomes 1, 7, 9, 11, 15, and 17 and further DNA probes for 5p13, 5q31, Rb-gene (13q14), cyclin D1 gene (11q13), and p53 gene (17p13). The aberration rate differed between 14% and 71% on bone marrow smears. Using the combination of MGG and FISH we analyzed eight patients. A total of 2622 bone marrow cells were morphologically identified and investigated for their specific chromosomal aberrations. For all probes applied, 57 cells of the erythropoietic lineage, 698 cells of the granulopoietic lineage, and 168 lymphocytes showed two normal FISH signals. Of 1723 nuclei of plasma cells, 464 (26.9%) were also not aberrant, whereas all other nuclei of plasma cells (n=1259, 73%) showed a specific aberration. Combination of fluorescence immunophenotyping and in situ hybridization (FICTION) was applied in 10 of 11 patients. Seventy eight investigated CD34-positive precursor cells did not show any specific aberration detected before in the plasma cell compartment. In conclusion, the combination of MGG and FISH on a single cell level demonstrated that only plasma cells bore the chromosomal aberration and MM did not evolve at an early cell level. PMID- 11757726 TI - Prevalence of blood-borne viral infections (cytomegalovirus, human herpesvirus-6, human herpesvirus-7, human herpesvirus-8, human T-cell lymphotropic virus-I/II, human retrovirus-5) among blood donors in Latvia. AB - The identification of blood-borne viral infections is important in transfusion medicine. The aim of this study was to evaluate the prevalence of human herpesvirus (HHV) [cytomegalovirus (CMV), HHV-6, HHV-7 HHV-8] and human retrovirus (HRV) (human T-cell lymphotropic virus (HTLV)-I/II, HRV-5) infections among apparently healthy Latvian blood donors. DNA extracted from peripheral blood leukocytes (PBL) of 150 individuals was tested for herpesviruses by sensitive polymerase chain reaction (PCR) technique. None of the blood donors was positive for HHV-8 infection, while the incidence of latent beta-herpesvirus infections was high: single infection by CMV, HHV-6, and HHV-7 was detected in 2.6%, 8.0%, and 43.3% of blood donors, respectively. Simultaneous dual and triple infections of these viruses were observed in 28.0% and 4.7% of individuals, respectively. Active infection by CMV and HHV-6 was not found, but HHV-7 DNA was present in plasma of 10.6% of the blood donors. While all blood donors were HTLV II and HRV-5 negative, 4.6% of HTLV-I seronegative blood donors were positive for the HTLV-I tax gene, although none of them harbored sequences for structural genes of the provirus. Based on our results, we conclude that monitoring of beta herpesvirus infections in blood donors can be important in cases of transfusions to immunocompromised persons. HHV-8, as well as the retroviruses HTLV-II and HRV 5, were not found in blood of Latvian blood donors. More investigations are required to explain the presence of the HTLV-I tax sequence in seronegative blood donors. PMID- 11757727 TI - Lethal pneumococcal infection in an 18-month-old girl with splenic hypoplasia and dysgammaglobulinemia. AB - We report the case of an 18-month-old girl who died of overwhelming pneumococcal sepsis. Autopsy revealed a small spleen with unusual architecture. There was a marked rarefaction of the white pulp with only very few but florid germinal centers. Immunohistochemical staining showed a low number of T and B lymphocytes in the spleen, whereas normal numbers and distribution of lymphocytes were found in all other primary and secondary lymphatic organs. Whereas levels of IgM were normal, IgA and IgG levels were significantly lower than in age-matched controls. Consistent with serological data, B cells mainly expressed IgM and IgD, whereas IgG expression was lower than expected. Additionally, intestinal immunoglobulin distribution in B-cell areas of lymphofollicular hyperplasia showed normal expression of IgM, but almost no expression of IgA. A review of the literature failed to disclose a similar case of dysgammaglobulinemia associated with isolated structural spleen anomalies. We propose that the patient suffered from a defect of the B-cell differentiation pathway. PMID- 11757728 TI - Acute anterior myocardial infarction as first manifestation of acute myeloid leukemia. AB - A 42-year-old man was admitted with heavy retrosternal pain lasting 30 min. Electrocardiography showed typical signs of acute anterior myocardial infarction. The patient reported only attacks of coughing for a couple of days, and no serious diseases. The physical examination was normal. Laboratory tests showed a white blood cell count of 45/nl, platelet count of 58/nl, and hemoglobin of 14.4 g/dl. Blood chemistry showed elevated lactic dehydrogenase (413 U/l) but no elevation in creatine phosphokinase or glutamic-oxaloacetic transaminase. Therefore no thrombolysis was administered, but coronary angiography was performed. This showed a long-distance, subtotal thrombotic occlusion of the left anterior descending artery. After percutaneous transluminal coronary angioplasty and implantation of serial stents a normal perfusion of the artery was observed. The patient's blood and bone marrow films revealed acute myeloid leukemia FAB M2. Various conditions can cause a myocardial infarction in leukemias. We discuss the clinical management and the possible reasons for a subtotal thrombotic occlusion of the coronary artery. PMID- 11757729 TI - A man with hereditary exostoses and high-grade non-Hodgkin's lymphoma of the bone. AB - Multiple cartilaginous exostoses (MCE) is an autosomal dominant disorder that can lead to malignant transformation from exostoses to a secondary chondrosarcoma. We present a case report of a 52-year-old man with MCE who had a palpable mass at the left shoulder. At the site of the left proximal humerus, a cartilaginous exostosis was localized, suggesting that the tumor developed by a malignant transformation of an exostosis into a secondary chondrosarcoma. Interestingly, a biopsy showed a diffuse large B-cell lymphoma with Burkitt-like features. To our knowledge, the association of high-grade lymphoma and hereditary exostoses has not been described previously. This case demonstrates that a malignant tumor at the location of a cartilaginous exostosis is not necessarily a chondrosarcoma and that a biopsy is an essential part of the diagnostic work-up. PMID- 11757731 TI - Surgery-associated acquired hemophilia A. AB - We present two patients who acquired factor VIII antibodies in the immediate postoperative period. One patient was receiving warfarin that was temporarily discontinued but reintroduced after the procedure. Preoperatively, none gave a history of bleeding, even with past surgeries, and both had normal coagulation tests. Within days of surgery, hemorrhage with prolonged activated partial thromboplastin time, low factor VIII levels, and demonstrable factor VIII antibodies were observed. For the patient who was receiving warfarin the severe bleeding was attributed, at the beginning, only to the high international normalized ratio (INR), which resulted in a fatal delay in diagnosis and appropriate treatment. We would like to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, severe bleeding but potential successful outcome with combined hemostatic control with recombinant activated FVII (rFVIIa) and elimination of the antibody by immunosuppression. PMID- 11757730 TI - Association of CD4+/CD56+/CD57+/CD8+(dim) large granular lymphocytic leukemia, splenic B-cell lymphoma with circulating villous lymphocytes, and idiopathic erythrocytosis. AB - In this paper we report a rare association of a splenic marginal zone B-cell lymphoma with villous lymphocytes and a T-cell large granular lymphocytic leukemia coexpressing CD4 and CD8 as well as CD56 and CD57 natural killer associated markers in an asymptomatic patient investigated because of an occasional finding of erythrocytosis and leukocytosis in routine blood analysis. We also discuss the possible reasons for this particular association. PMID- 11757732 TI - Isoproturon degradation as affected by the growth of two algal species at different concentrations and pH values. AB - Metabolism of [14C-u-phenyl]isoproturon [3-(4-isopropylphenyl)-1,1-dimethylurea] by two soil and freshwater microorganisms, green alga Chlorella kesslerei and cyanobacterium Anabaena inaequalis, was studied as a function of pH, pesticide concentration, and incubation time. Metabolized isoproturon, in the media, ranged from 0% (Chlorella at pH 5.5 after 1 d) to 22% (Anabaena at pH 5.5 after 10 d). Twenty-five percent faster degradation of isoproturon by Anabaena occurred at pH 5.5 versus pH 7.5, when measured over 10 d. Increased 14C incorporation into tissue, with time and at lower pH, was due mainly to bioaccumulation of [14C]isoproturon and/or its metabolites in the cells. Metabolic degradation resulted in four identifiable (by TLC) metabolites. Based on this, a degradation pathway is proposed, involving mono- and di-N-demethylation, hydroxylation of the isopropyl moiety, and hydrolysis to 4-isopropylaniline. Similarity in the metabolites produced suggests that the enzyme systems responsible for metabolizing isoproturon are almost identical in both photosynthetic micro-algae. PMID- 11757733 TI - Degradation of isoxaben in soils and an aqueous system. AB - The degradation of isoxaben [N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6 dimethoxybenzamide] was studied in soil and in an aqueous system. Soil studies were conducted in Erlenmeyer flasks (treated with 1 microg/g isoxaben) and mineralization studies in Biometer flasks (treated with 1 microg/g unlabeled and 14C-isoxaben) incubated at 23 C. Degradation in the aqueous system was performed in Erlenmeyer flasks under aerobic and anaerobic conditions incubated at 23 degrees C. Incubation mixtures were extracted at selected times and analyzed for isoxaben and degradation products by HPLC with product identification confirmed by GC-MS. After 8 weeks, 78% and 23% of the total isoxaben disappeared in nonsterile and sterile soils, respectively. After 12 weeks, approximately 1% of the labeled isoxaben was recovered as CO2 in the Biometer flask experiments; no volatile products were detected, and 5% and 33% of the total radioactivity was recovered from the nonsterile and sterile soils, respectively. In the aquatic system after 8 weeks, isoxaben had decreased from 1microg/g to 0.1 and 0.004 microg/g under aerobic and anaerobic conditions, respectively. Degradation products detected from the soil studies were 3-nitrophthalic acid and 4 methoxyphenol, and 3-nitrophthalic acid in the aqueous system studies. Microbial activity was considered to be a major factor in the degradation of isoxaben in this study. PMID- 11757734 TI - Behavior of triadimefon in two Lebanese soils. AB - The retention and fate of triadimefon fungicide were studied under two environmental conditions. Field studies were conducted on two soils, a sandy loam soil (Fanar) and a clay soil (Raouda). Fanar is a wet coastal area while Raouda is a dry agricultural area of the Bekaa plain located at an elevation of 870 m above sea level. Triadimefon was applied with a jet sprayer at 267 g a.i.ha(-1) and 200 g a.i.ha(-1) at Fanar and Raouda, respectively. Reconstituted soil columns (600 x 30 mm) glasses, were used to study the fungicide movement and metabolism in the two soils. Analyses of triadimefon and its metabolites were carried out using gas chromatography (GC) and high performance liquid chromatography (HPLC). The results indicated a weak reversibility of the adsorbed fraction in the clay soil. Clay is considered an important factor in triadimefon adsorption. Triadimefon mobility in the sandy-loam soil was relatively high in comparison with behavior in the clay soil where about half of the applied fungicide was detected in the upper 25 cm of soil, six days after treatment. Rapid degradation of triadimefon to triadimenol was observed in the two soils. The observed half-life was 8 days in sandy-loam and 13 days in clay soils. PMID- 11757735 TI - Determination of 2,4-dichlorophenoxyacetic acid (2,4-D) in human urine with mass selective detection. AB - Method development and validation studies have been completed on an assay that will allow the determination of 2,4-dichlorophenoxyacetic acid (2,4-D) in human urine. The accurate determination of 2,4-D in urine is an important factor in monitoring worker and population exposure. These studies successfully validated a method for the detection of 2,4-D in urine at a limit of quantitation (LOQ) of 5.00 ppb (parts per billion) using gas chromatography with mass selective detection (GC/MSD). The first study involved the determination of 2,4-D in control human urine and urine samples fortified with 2,4-D. Due to chromatographic interference, a second study was conducted using 14C-2,4-D to verify the recoverability of 2,4-D from human urine at low levels using the GC/MSD method. The second study supports the results of the original data. The 2,4-D was extracted from human urine using a procedure involving hydrolysis using potassium hydroxide, followed by a liquid-liquid extraction into methylene chloride. The extracted samples were derivatized with diazomethane. The methylated fraction was analyzed by GC/MSD. Quantitation was made by comparison to methylated reference standards of 2,4-D. Aliquots fortified at 5-, 50-, and 500-ppb levels were analyzed. The overall mean recovery for all fortified samples was 90.3% with a relative standard deviation of 14.31%. PMID- 11757736 TI - Comparison of gas chromatography and immunoassay methods in measuring the distribution of dieldrin in rainbow trout tissues. AB - Studies have been conducted to determine the distribution of dieldrin in various tissues of rainbow trout when exposed to several dieldrin concentrations. Medium sized fish with an average weight and length of 195.4 +/- 30.5 g and 25.7 +/- 1.4 cm, respectively, were placed in groups of 6 in 300 L tanks containing purified and aerated water and maintained at 10 degrees C. Following an acclimatization period of 10 days, each group of fish was exposed to one of four dieldrin concentrations ranging from 50 to 80 ppb. After 24 hours, the fish were taken out of the tanks and sacrificed. The brain, gills, liver, muscles and skin were collected from each fish. Dieldrin was extracted from each tissue using SPE techniques and analyzed by both gas chromatography (GC) and enzyme linked immunosorbent assay (ELISA). Results of analyses by the two techniques were highly correlated. The results also showed that liver and skin tissues had the highest level of dieldrin residues. In comparing the means of the six fish samples, it was found that liver or skin contained about 1.5-fold the level in brain, about 4.0 fold the level in muscles and about 6.5 fold the level in gills. Immunoassay proved to be as reliable an analytical tool as gas chromatography in this case. PMID- 11757737 TI - Differential effects of the herbicides bensulfuron and cinosulfuron on soil microorganisms. AB - Bensulfuron toxicity on soil microbes was evaluated by the methods used in a previous study on cinosulfuron; the effects of the two sulfonylureas were compared. Cinosulfuron and bensulfuron, at the normal field application rate and 100 times higher, had no effect on the total number of bacteria and nitrifiers, or on the respiration activity in the soil, but they did decrease the nitrification activity. In vitro toxicity tests carried out on representative soil microbial strains using bensulfuron at 50 mg l(-1) showed some inhibition of three of the 17 bacterial strains and strong inhibition of almost all the 12 fungal strains; cinosulfuron had had no effect on any of these strains in the previous study. It is concluded that, compared with cinosulfuron, bensulfuron is potentially more toxic on soil heterotrophic microorganisms, but only at very high concentrations that are nearly impossible to reach with the usual agricultural use of the herbicides. However, autotrophic nitrifiers were more sensitive to both sulfonylureas than the other microorganisms. PMID- 11757738 TI - Effect of diazinon on behavior of Japanese medaka (Oryzias latipes) and gene expression of tyrosine hydroxylase as a biomarker. AB - This paper reports on the development of a biomarker used to monitor abnormal behaviors caused by diazinon in Japanese medaka (Oryzias latipes) as a model organism. Tyrosine hydroxylase (TH) activity in tissues was measured and the TH enzyme production in specific organs using a in situ cytochemical technique was monitored. These data were comparatively analyzed with those from semi quantitative RT-PCR utilizing medaka TH gene that could be a potential biomarker for neuronal modulations and behaviors. For monitoring experiments at behavioral and molecular biological levels, the fish were treated under different sublethal conditions of diazinon (O, O-diethyl O-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] phosphorothioate) and their behavioral responses were observed. There were no significant differences in activity of TH head and body portions when the fish were exposed to lower concentrations (0.5-10 ppb) of diazinon including control treatment (0 ppb) for 24 hr. In temporal change of TH activity at 100 ppb diazinon treatment, however, the activity of body portion appeared to be inhibited during the first 30 min exposure but later seemed to recover slightly after 1 hr. TH appeared to be expressed mainly in the olfactory bulb, midbrain and brain stem regions as assessed by in situ immunohistochemistry. The treatment (1000 ppb) significantly suppressed TH protein production in the olfactory bulb, midbrain and brain stem regions. In kidney from the body portion the higher concentration treatment (1000 ppb) caused little suppression compared with the control. The RT-PCR showed that a production of TH mRNA transcript was significantly inhibited at 5 ppm diazinon treatment in the body portion. It was concluded that a suppression of TH activity would be one of the causes for the abnormal behaviors of the medaka that could be quantitatively monitored using an image processing system. This study provides molecular and neurobehavioral bases of a biomonitoring system for toxic chemicals using a model organism such as fish. PMID- 11757739 TI - Sorption and desorption of the herbicide alachlor on humic acid fractions from two vermicomposts. AB - The present study focuses on the analysis of two vermicomposts, that have been used as alternative sources of restitution of soil organic matter, as well as sources of nutrient replacements. For this purpose, two samples of vermicomposts from different Brazilian regions (Sao Carlos-SP and Londrina-PR) were characterized according to their humic acid content. Both samples had a pH value near 7.0, and the humic acids present showed high cationic exchange capacities and low values for the C/N ratios. The infrared spectra showed bands that suggested the presence of aliphatic and aromatic components bound to phenolic, carboxylic and amide groups. The effect of vermicompost added to soil on the application of alachlor was evaluated. Alachlor sorption, Freundlich isotherms and alachlor desorption curves in the soil matrix and the vermicompost/soil mixture matrix were determined. PMID- 11757740 TI - Simazine removal from water in a continuous bubble column by O3 and O3/H2O2. AB - Simazine, [2-chloro, 4,6-bis(ethylamino)-1,3,5-s-triazine], a common herbicide found in surface and ground water has been ozonized in continuous flow mode. Typical operating variables in ozonation processes have been investigated. Thus, the ozone dose fed to the system exerted a positive effect, while the gas flow rate did not influence the efficiency of the process provided ozone mass flow rate was kept constant. Increasing the pH led to a higher extension of the free radical degradation of simazine and, therefore, to a higher efficiency of the process. Also, addition of free radical promoters, i.e. hydrogen peroxide, did result in a significant improvement of the simazine removal rate. A first approach to process economy showed the system ozone/hydrogen peroxide as the most advantageous in terms of electrical energy requirements. PMID- 11757741 TI - Evaluating environmental hazards of land applying composted diazinon using earthworm bioassays. AB - Environmental hazards resulting from land application of composted pesticide residue have not been rigorously evaluated. This study was conducted to examine the toxicity of a composted pesticide residue using earthworms (Eisenia foetida Savigny) as a microinvertebrate model in a soil bioassay system. Diazinon, which was used in these experiments as a test pesticide, was removed from simulated rinsate (wastewater) by sorption onto peat moss. Following the rinsate clean-up phase, diazinon-laden peat moss was placed into bioreactors and composted for either 30 or 60 days. Earthworms were then exposed to soil amended with the composted material. Mortality and symptomatic effects characteristic of acetylcholinesterase inhibition, including weight loss, reduced burying ability and curling, occurred in earthworms exposed to soil amended with either uncomposted or 30-day composted diazinon, but not in those exposed to soil amended with 60-day composted diazinon. The amount of solvent-extractable diazinon from compost was not directly related to acute earthworm toxicity based on the selected criteria. These results indicated a reduction in diazinon bioavailability during latter 30 d of composting that did not correspond to a reduction in solvent-extractable diazinon concentrations. Measuring symptomatic effects of xenobiotics as described in this study may increase the sensitivity and diagnostic ability of earthworm bioassays. PMID- 11757742 TI - Production and quantification of methyl ketones in wild tomato accessions. AB - Production of methyl ketones as naturally occurring insecticides from wild tomato accessions is explored in this study. Density of two glandular trichomes (type IV and type VI) on the leaves of six wild tomato accessions of Lycopersicon hirsutum f. glabratum (Mull); three accessions of L. hirsutum f. typicum (Humb & Bonpl.); two accessions of L. pennellii Corr. (D'Arcy); and density of type VI glandular trichomes of the commercial tomato Lycopersicon esculentum cv. Fabulous are reported. Densities of type IV and VI glandular trichomes varied among the accessions tested. Type IV trichomes occurred at much higher densities than type VI. Over all accessions and counting trichome densities on both abaxial and adaxial leaflet surfaces, type IV densities averaged 96,378 trichomes.g(-1) leaflets while type VI densities averaged 67,350 trichomes.g(-1) leaflets. Concentrations of four methyl ketones (2-tridecanone, 2-dodecanone, 2-undecanone, 2-pentadecanone) were determined per unit leaf surface area (mm2) and per g fresh leaflets. Concentrations of total methyl ketones ranged from 81.3 microg.g(-1) fresh leaflets on L. esculentum cv. Fabulous to 5.5 mg.g(-1) on L. hirsutum f. glabratum (PI 134417). Two methyl ketones, 2-undecanone and 2-tridecanone, predominated trichome secretions in five of the L. hirsutum f. glabratum accessions tested (PI 251304, PI 126449, PI 134417, PI 134418, and LA 407). PMID- 11757743 TI - Total arsenic accumulation in edible pods and seeds of Phaseolus vulgaris. AB - The main objective of this study was to evaluate whether arsenic accumulated in the edible pods and seeds of Phaseolus vulgaris, cv. Helda, above the Spanish maximum recommended concentration for food crops, 1 mg kg(-1) on a fresh weight basis. Only organic arsenicals were used because they are: a) the only arsenic species allowed for agricultural applications and b) more mobile than inorganic species. Selection of French beans, a sensitive plant to arsenic, was based on the fact that arsenic upward translocation is higher in sensitive than in tolerant plants. A 2 x 3 factorial experiment was conducted with two organic arsenic species: methylarsonic acid (MAA) or dimethylarsinic acid (DMAA) and three arsenic concentrations: 0.2, 0.5, or 1.0 mg L(-1). Arsenic phytotoxicity was primarily determined by soluble arsenic concentration. Experimental results showed that the low bean plant tolerance to arsenic is possibly due to the high arsenic upward transport to shoots, which could result in profound negative metabolic consequences. Even under extremely adverse conditions, arsenic residues in edible beans were below the maximum statutory limit set by the Spanish legislation. It can be concluded that the major danger of organic arsenical herbicides is that of decreased productivity rather than high arsenic uptake by consumers. PMID- 11757744 TI - Helicobacter pylori and nonsteroidal anti-inflammatory drugs. Approaching the end of the controversy in the new millennium, or room for more debate? PMID- 11757745 TI - Prevalence of Helicobacter pylori infection and correlation between severity of upper gastrointestinal lesions and H. pylori infection in Japanese patients with Crohn's disease. AB - BACKGROUND: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection. METHODS: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed. RESULTS: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002). CONCLUSIONS: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics. PMID- 11757746 TI - Multiple colorectal cancers in the elderly: a retrospective study of both surgical and autopsy cases. AB - BACKGROUND: Multiple primary cancers are not rare events in the large intestine, and account for approximately 5-7% of patients with colorectal cancer (CRC). There are few reports demonstrating clinicopathologic features of multiple CRCs in the elderly. METHODS: We clinicopathologically investigated 947 surgical patients and 362 autopsy samples from patients aged 65 years or more with CRC, including 81 surgical and 34 autopsy cases of multiple CRCs. We compared the data in the very old group (age > or = 85 years) with those of the younger age groups, i.e., a young-old group (65-74 years) and a middle-old group (75-84 years). RESULTS: The proportion of multiple CRCs was 8.6% (81/947) in the surgical patients and 9.4% (34/362) in the autopsy cases, with no significant difference among the three age groups. Similar site distributions and sex ratios, indicating proximal shift and female predominance with advancing age, were found in multiple and single CRCs, except for autopsy cases with multiple CRCs. Multiple CRCs in nonadjacent segments of the large intestine accounted for 11% (9/81) in surgical cases and 35% (12/34) in autopsy cases. In autopsy cases, the incidence of extracolorectal malignancies in patients with a single CRC was 22% (17/76) in the young-old group, 27% (39/147) in the middle-old group, and 35% (37/105) in the very old group, whereas the incidences in patients with multiple CRCs were 25% (1/4), 11% (2/18), and 50% (6/12), respectively. Regarding the organs with extracolorectal malignancies, the stomach (29%) was most frequent, followed by lung (14%), hematopoietic system (12%), and pancreatobiliary system (10%). CONCLUSIONS: These results indicate that the incidence of multiple CRCs in elderly patients with CRC is approximately 8%-10%, with no age-related difference, while extracolorectal malignancies increase with advancing age. PMID- 11757747 TI - Relationship between hepatitis C virus infection and schistosomal liver disease: not simply an additive effect. AB - BACKGROUND: To study the association, clinical significance, and impact of hepatitis C virus (HCV) co-infection in patients with schistosomal liver disease (SLD). METHODS: A total of 240 patients with chronic liver diseases encountered consecutively were enrolled in the study. Fifty volunteer blood donors were enrolled as controls. HCV antibody determination (enzyme-linked immunosorbent assay), qualitative and quantitative HCV RNA assay (reverse transcriptase polymerase chain reaction), and HCV genotyping (line probe assay) were performed. RESULTS: Twenty-eight patients had SLD alone, 60 had both SLD and chronic hepatitis C (CH-C), 120 had CH-C alone, and 32 had other liver diseases. The positivity rates for HCV antibody (76% vs 20%; P < 0.001) and HCV RNA (59% vs 10%; P < 0.001) were significantly higher in the patients with SLD (n = 88) than in the volunteer blood donors (n = 50). Complications of liver cirrhosis were more common in patients with concomitant SLD and CH-C than in those with either SLD or CH-C alone. The mean levels of alanine aminotransferase (77 +/- 42 vs 93 +/- 55 IU/l; P = 0.049) and HCV RNA concentrations (3.5 +/- 1.0 vs 4.2 +/- 1.0 log copy/ml; P < 0.001) were significantly lower in patients with concomitant SLD and CH-C than in those with CH-C alone. HCV genotype 4 predominated in both these groups (93% and 98%). CONCLUSIONS: SLD in Egypt is significantly associated with HCV infection, with the predominance of genotype 4. Concurrent HCV infection and SLD result in much more severe liver disease than that seen with either disease alone. However, the activity of HCV infection seems to be partially suppressed in patients with SLD. PMID- 11757748 TI - Treatment of chronic hepatitis C patients with amantadine. AB - BACKGROUND: Amantadine was reported to decrease serum alanine aminotransferase and HCV RNA levels in chronic hepatitis C patients who had not respond to interferon, but further experience has produced mixed results. The aim of this study was to investigate the efficacy and safety of amantadine in a larger number of patients with chronic hepatitis C. METHODS: Fifty-eight consecutive patients with chronic hepatitis C were enrolled in this open-label prospective study. The patients had either received no antiviral agents or interferon therapy had previously failed. RESULTS: In 85% of the patients, the time-relation between therapy and reduction of serum aminotransferase levels suggested a potential anti inflammatory activity of the drug without an effect on viremia. Seven patients discontinued the therapy because of side effects, and overall, side effects were observed in 31% of patients. CONCLUSIONS: Amantadine monotherapy in chronic hepatitis C patients may be effective in terms of reducing biochemical markers, but this effect was not associated with loss of viremia. PMID- 11757749 TI - Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice. AB - BACKGROUND: The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells. METHODS: Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation. RESULTS: About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells. CONCLUSIONS: These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC. PMID- 11757750 TI - Malignant schwannoma of the esophagus with lymph node metastasis: literature review of schwannoma of the esophagus. AB - An extremely rare case of malignant schwannoma of the esophagus with lymph node metastasis is reported. A 49-year-old woman was found to have an abnormal shadow on a chest X-ray film taken during an annual checkup. Upper gastrointestinal series showed extrinsic pressure on the middle thoracic esophagus, without a mucosal lesion. An exploratory operation was performed, with a tentative diagnosis of esophageal leiomyoma. The tumor was enucleated with part of the esophageal mucosa, and a few enlarged lymph nodes around the tumor were dissected. The resected tumor was an elastic firm mass, measuring 8.2 x 5.8 x 3.7 cm, and had a smooth surface. Histological examination of the tumor revealed the proliferation of spindle-shaped cells with chromatin-rich nuclei. The nuclei were variable in size and showed remarkable atypia. A paraesophageal lymph node had same findings as the main tumor. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein and neuron-specific enolase. The pathological diagnosis of this tumor was malignant esophageal schwannoma with lymph node metastasis. Esophageal schwannoma is extremely rare. We reviewed the literature on 19 cases of esophageal schwannoma, including that in our patient. The majority of the tumors were benign. Only three cases of schwannoma were malignant, and this is the first reported case of malignant schwannoma with lymph node metastasis. PMID- 11757751 TI - Complete regression of colonic adenomas after treatment with sulindac in Gardner's syndrome: a 4-year follow-up. AB - A 22-year-old woman with Gardner's syndrome in whom long-term sulindac therapy, without surgical treatment, was effective in inducing complete regression of colonic adenomas is reported. One hundred milligrams of sulindac was administered twice daily after endoscopic polypectomy. Follow-up colonoscopy 6 months later revealed an encouraging regression of colonic adenomas. The tumors had disappeared after 40 months of sulindac treatment. A sustained effect was identified even after 51 months. Ten milligrams of famotidine was coadministered to prevent side effects of sulindac. Although the effect of sulindac on colorectal adenomas may be transient, this therapy may be useful for postponing prophylactic colectomy, especially for the sparse type of familial adenomatous polyposis. PMID- 11757752 TI - Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia. AB - We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects. PMID- 11757753 TI - Usefulness of MR imaging in the postsurgical monitoring of gallbladder cancer in a patient with bile duct cancer that developed 7 years after resection of mucinous adenocarcinoma of the gallbladder. AB - We encountered a case of left hepatic duct cancer that developed 7 years after surgical resection of early-stage adenocarcinoma of the gallbladder. A 65-year old woman was hospitalized with high fever and general fatigue. She also had elevated serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, and carbohydrate antigen 19-9. Seven years earlier, she had undergone extended cholecystectomy and resection of the extrahepatic bile duct for early-stage mucinous adenocarcinoma of the gallbladder. Conventional examinations did not reveal any responsible lesions. Magnetic resonance (MR) cholangiography, however, showed a tumor obstructing the left hepatic duct, and dynamic MR images revealed multiple foci of bacterial abscess in the liver. Surgically resected tissue again revealed mucinous adenocarcinoma. The present case is rare in that metachronous mucinous adenocarcinoma of the biliary system occurred after a long interval. This case suggests the usefulness of MR imaging in the postsurgical monitoring of patients with gallbladder carcinoma. PMID- 11757754 TI - Pill-induced esophagitis caused by lansoprazole. PMID- 11757755 TI - Efficacy of amantadine hydrochloride in patients with chronic hepatitis C. PMID- 11757756 TI - Dendritic cell-based immunotherapy for hepatocellular carcinoma. PMID- 11757757 TI - The necessity of renal biopsies in the management of diabetic nephropathy. PMID- 11757758 TI - Increasing incidence of invasive pulmonary aspergillosis and its early diagnosis. PMID- 11757759 TI - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in Japan. PMID- 11757760 TI - Evaluation of renal biopsy samples of patients with diabetic nephropathy. AB - OBJECTIVE: To evaluate the usefulness of renal biopsy in the overall management of patients with diabetes mellitus (DM), we examined the relationship between the clinical parameters and histopathological findings of renal biopsy samples. METHODS: Renal biopsy specimens were obtained from 109 type 2 diabetic patients with proteinuria. Samples were divided into the following two groups: Diabetic Nephropathy (DN) group (n=80) had typical diabetic lesions without other renal diseases, complication group (n=29) had diabetic lesions with other renal diseases. Furthermore, DN group was subdivided into two subgroups: slow progressive group (SP group, n=32), the level of serum creatinine (s-Cr) was normal at the time of renal biopsy and three years after renal biopsy, and fast progressive group (FP group, n=14), the level of s-Cr was normal at the time of renal biopsy but more than doubled three years after renal biopsy. RESULTS: The level of total protein was significantly lower and HbA1c significantly higher in the DN group than in the Complication group. However, other clinical parameters were not significantly different between the two groups. Urinary protein, systolic and diastolic blood pressure in FP group were significantly higher than in SP group. The percentage of sclerotic glomeruli, the severity of mesangial expansion, tubular injury and cell infiltration were significantly greater in FP than in SP group. CONCLUSIONS: Our results indicated that a complete evaluation of renal pathology in DM could not be made by clinical parameters only, and that the progression of DN could be accurately predicted by histopathological evaluation. Therefore, this study emphasizes the importance of renal biopsy in the overall management of patients with DM and/or DN. PMID- 11757761 TI - Activated platelets and endothelial cell interaction with neutrophils under flow conditions. AB - OBJECTIVE: The mechanism of neutrophil adhesion to the endothelium during the earliest stages of acute inflammation, especially before the induction of adhesion molecules on endothelial cells, remains unknown. We studied the possible involvement of platelets in this process. METHODS: Neutrophils were added to human umbilical vein-derived endothelial cells (HUVEC) with or without adherent platelets in the presence or absence of adhesion-blocking monoclonal antibodies (mAbs). Adhesion of neutrophils to HUVEC at dynamic flow conditions was assessed using a flow chamber. RESULTS: 1) Thrombin-activated platelets adhered to resting HUVEC at dynamic flow conditions through platelet glycoprotein IIb/IIIa and RGD proteins. 2) Neutrophils tethered to P-selectin induced on thrombin-activated platelets, which were immobilized on HUVEC. 3) Activated neutrophils adhered, via LFA-1, to ICAM-1 on HUVEC. 4) Activated platelets induced interleukin (IL)-8 secretion by HUVEC. CONCLUSIONS: Immobilized platelets on the vessel wall with induced P-selectin on the surface biochemically and functionally promote the adhesion of neutrophils to endothelial cells. PMID- 11757762 TI - Serum levels of KL-6 reflect disease activity of interstitial pneumonia associated with ANCA-related vasculitis. AB - OBJECTIVE: KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti neutrophil cytoplasmic antibody (ANCA)-related vasculitis. METHODS: Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. PATIENTS: We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. RESULTS: Serum levels of KL-6 in ANCA positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA-positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. CONCLUSION: These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis. PMID- 11757763 TI - Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis. AB - We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take. PMID- 11757764 TI - An autopsy case of primary biliary cirrhosis with severe interstitial pneumonia. AB - A 74-year-old woman was admitted to our hospital because of interstitial pneumonia. She had a 14-year history of primary biliary cirrhosis (PBC) diagnosed histologically, with a positive test for anti-mitochondrial antibodies and elevated biliary enzyme activity. She also had a 7-year history of rheumatoid arthritis and a 26-year history of Sjogren's syndrome. Though the symptoms of these complications improved, the interstitial pneumonia deteriorated very quickly and the patient died of respiratory failure due to acute exacerbation of interstitial pneumonia when the activity of PBC decreased. We report this case because it is relatively rare for PBC to be complicated by severe interstitial pneumonia, and it may offer insight into the etiology of these diseases. PMID- 11757765 TI - Polymyositis, pulmonary fibrosis and malignant lymphoma associated with hepatitis C virus infection. AB - Polymyositis has been associated with various viral infections, and a spectrum of immune-related diseases may occur with hepatitis C (HCV) infection. Both polymyositis and HCV infection may be accompanied by pulmonary fibrosis. An association between polymyositis and malignancy has also been reported. We report a 55-year-old woman accompanied cryoglobulinemia with HCV infection and manifesting polymyositis, pulmonary fibrosis and malignant lymphoma. Steroid therapy was effective to improve interstitial pneumonia, polymyositis, and liver function. PMID- 11757766 TI - Congestive heart failure caused by aortocaval fistula after nephrectomy. AB - We treated a 66-year-old man and a 69-year-old woman with high output cardiac failure due to aortocaval fistula. They underwent nephrectomy 40 and 36 years ago, respectively. They suffered from heart failure for a very long time. However, the etiology was not elucidated until recently. The aortogram revealed massive shunt from the aorta to the inferior vena cava via the right renal artery. Three-dimensional computerized tomography clearly delineated the aortocaval fistula. Surgical closure of the fistula promptly improved heart failure. We stress the importance of history taking concerning nephrectomy and the importance of abdominal auscultation in high output cardiac failure. PMID- 11757767 TI - Pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease. AB - A 63-year-old man who had experienced cerebral infarction and myocardial infarction at an early age, and repeatedly underwent coronary angioplasty was admitted to our hospital for cardiac evaluation. A coronary angiography showed complex multi-vessel disease with significant stenosis in all major vessels and coronary-artery bypass grafts. A funduscopic examination to evaluate hypertensive and diabetic changes revealed angioid streaks. Therefore, a skin biopsy was performed despite the absence of characteristic skin lesions. Histopathologic examinations revealed calcification and fragmentation of elastic fibers. Therefore, he was finally diagnosed as having pseudoxanthoma elasticum 25 years after the onset of cardiovascular disease. PMID- 11757768 TI - Long-term treatment of ischemic dilated cardiomyopathy with continuous positive airway pressure. AB - An 81-year-old man with ischemic dilated cardiomyopathy complained of frequently awakening from sleep due to choking; subsequent polysomnography revealed Cheyne Stokes respiration (CSR) with sleep apnea. With continuous positive airway pressure (CPAP) through a nasal mask, both the CSR and symptoms disappeared. After 6-12 months, chest X-ray and echocardiographic findings continued to improve without any change in pharmacological treatment. For three years, CPAP had been effective to eliminate CSR during sleep. Long-term CPAP treatment, which is rarely applied for congestive heart failure in Japan, is useful in alleviating the adverse effects of CSR and, thereby, maintaining a good quality of life in these patients. PMID- 11757769 TI - Invasive pulmonary aspergillosis in a puerperant with drug-induced agranulocytosis. AB - Invasive pulmonary aspergillosis (IPA) is an acute infection of Aspergillus species to the lungs. It generally occurs in immunocompromised hosts, especially with neutropenia. We report a 30-year-old puerperant, who developed IPA from agranulocytosis. She had been treated for threatened labor with ritodrine and cefepime, one of which induced agranulocytosis. After vaginal delivery of twins, pneumonia emerged in the right lower lobe. She was diagnosed to have IPA according to the halo sign on computed tomography (CT) and positive circulating antibody against Aspergillus, and was treated successfully with oral itraconazole followed by surgical resection. It is important to note that IPA might arise in otherwise immunocompetent hosts when neutropenia is long-standing. PMID- 11757770 TI - Chronic hypersensitivity pneumonitis induced by Shiitake mushroom spores associated with lung cancer. AB - A 61-year-old man was admitted to our hospital with a 6-month history of productive cough. He, along with his wife, had been involved with Shiitake mushroom cultures for a period of 12 years. On admission, chest radiography showed bilateral fine-nodular shadow and CT scans showed reticulonodular opacities and a ground-glass appearance predominantly in the subpleural area in both lungs, and a mass in the left S6. Resected pathological specimens obtained by left lower lobectomy revealed lung adenosquamous carcinoma (stage IB), interstitial changes accompanied with lymphocyte proliferation and fibrosis, and granuloma with giant cells. Serum precipitins for Shiitake mushroom antigens were positive. The productive cough improved after the hospital admission and occurred again when he returned to work with the Shiitake mushroom production. Therefore, chronic hypersensitivity pneumonitis (HP) caused by Shiitake mushroom spores was diagnosed. Moreover, his wife was found to have HP caused by mushrooms at this time. There are only two previous reports of chronic HP caused by Shiitake mushroom in Japan, and this is the first case of chronic HP associated with lung cancer. PMID- 11757771 TI - Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide. AB - We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications. PMID- 11757772 TI - Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient. AB - A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards. PMID- 11757773 TI - Two Japanese CADASIL families with a R141C mutation in the Notch3 gene. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia with Notch3 gene mutations as the cause of the disease. To date, there are only a few Japanese families ever reported with a mutation in the gene. Here, we report two more Japanese CADASIL families carrying a missense mutation in the Notch3 gene (R141C) with a unique lesion in the corpus callosum. This is the first report of two unrelated Japanese CADASIL families with a R141C mutation in the Notch3 gene. Although the disease is very rare among the Japanese population, our result suggests a possible relationship of this particular mutation (R141C) with the lesions of the corpus callosum. PMID- 11757774 TI - Severe depression as an initial symptom in an elderly patient with acute disseminated encephalomyelitis. AB - We report a 63-year-old man with acute disseminated encephalomyelitis (ADEM), initially showing depression for one and a half months but subsequently meningoencephalitis followed by acute-onset myelopathy. Neuroradiological examinations of the brain demonstrated no focal lesion causative for his depression, while cerebrospinal fluid revealed elevated levels of inflammatory cytokines in parallel with disease activity. Because depression is usually a rare initial symptom for patients with ADEM, an increased production of inflammatory cytokines in the central nervous system as well as age-related alterations of immune response might have played an important role in the development of depression in this elderly patient. PMID- 11757775 TI - Fatal thoracic aortic aneurysm in a patient with childhood-onset vasculo-Behcet's disease: an autopsy report. AB - A 33-year-old man died following sudden unexpected rupture of a saccular thoracic aortic aneurysm. The patient had been treated as suspicious Behcet's disease (BD) for 9 years, however, the medication was discontinued at the age of 24. Autopsy disclosed multiple aneurysms at the descending thoracic and abdominal aorta. Histopathologically, infiltration of inflammatory cells and destruction with loss of elastic and muscle fibers of the aortic medial wall were seen. Taking the clinical course into account, all the postmortem findings were compatible with those of vasculo-BD. It is important that medical follow-up should be implemented even for childhood-onset patients who do not satisfy criteria of BD. PMID- 11757776 TI - Cognitive behavioral therapy and fasting therapy for a patient with chronic fatigue syndrome. AB - Cognitive behavioral therapy temporarily alleviated symptoms of a chronic fatigue syndrome patient but the anxiety about rehabilitation into work became stronger and his symptoms worsened. This patient was successfully rehabilitated by fasting therapy. Natural killer cell activity and serum acylcarnitine levels recovered after fasting therapy. Though fasting therapy transiently increased physical and mental subjective symptoms, the patient gained self-confidence by overcoming difficulties after fasting therapy. A combination of cognitive behavioral therapy and fasting therapy is promising as a treatment for chronic fatigue syndrome. PMID- 11757777 TI - Short-term administration of an essential trace elements preparation (Elemenmic) causes a high whole blood manganese concentration and manganese deposition in basal ganglia. PMID- 11757778 TI - Particle-mediated intravascular delivery of oligonucleotides to tumors: associated biology and lessons from genotherapy. AB - For a solid tumor to become life-threatening, an adequate blood supply has to be established. Although neovascularization has dire consequences for the host, it furnishes a common route through which tumors may be accessed and eradicated by drugs. The fact that a tumor's vasculature is relatively more permeable than that of healthy host tissue means selective delivery of drugs may be achieved. The role played by the cells making up the tumor vascular bed, vascular endothelial cells (VECs), has to be evaluated closely in attempts to design ways for enhancing drug delivery to solid tumors via the vasculature. The two major roles of VECs in the body, as barrier and as transport, are both highly pertinent to drug delivery. Our review examines how VECs may be manipulated in vivo to improve the selective delivery of carriers for oligonucleotide constructs to solid tumors. It also discusses how oligonucleotide drugs may be targeted against tumor VECs on the premise that by killing these cells, the tumor itself will perish. Cationic liposomes and microspheres are the major delivery vehicles discussed, with added analyses of such other nucleic acid carriers as nanospheres, dendrimers, and polyethyleneimine. PMID- 11757779 TI - A novel intravascular drug delivery method using endothelial biotinylation and avidin-biotin binding. AB - In this study, a novel intravascular drug delivery system was developed in which a drug injected from a catheter was fixed to the vasculature of the targeted tissue. Cellular proteins of viable endothelial cells were first biotinylated directly by biotinylation reagents, and then bound by an avidinated drug or, using avidin as a linker, a biotinylated drug. In the initial experiments, we studied in vitro the biotinylation of cultured bovine aortic endothelial cells (BAECs) by applying biotinylation reagents (NHS-LC-biotin or sulfo-NHS-LC-biotin) onto the washed intact BAEC monolayers and showed that the amount of biotin bound to the cells depended on the concentration of the biotinylation reagents applied. The cell-bound biotin decreased with time after the biotinylation. When fluorescein-labeled avidin (FITC-avidin) was applied to the biotinylated BAEC monolayers, the FITC-avidin readily bound to the cells. An LDH-release assay showed that sulfo-NHS-LC-biotin was only slightly cytotoxic to the BAECs and a colony formation assay showed only slight adverse effects of the reagent. In vivo studies were carried out on the renal arteries of normal rabbits. A solution of NHS-LC-biotin was injected through a catheter to one kidney to biotinylate its vasculature and the vehicle to the other as control, followed by a perfusion with saline. Finally, a solution of FITC-avidin was injected to both kidneys that were then reperfused with the blood flow following the withdrawal of the catheters. In the histological sections, more than 85% of glomeruli was stained with fluorescein in the biotinylated kidney, whereas no glomeruli were stained in the control. In the kidneys harvested 2 days after the same procedure, most glomeruli were still brightly stained. In the final experiment, biotinylated kidneys were injected with a solution of avidin, followed by a solution of fluorescein-biotin. Control kidneys had no prior biotinylation but received the same injections of avidin and fluorescein-biotin as above. More than 80% of glomeruli were stained in the biotinylated kidneys but none in the controls. This indicated that biotinylated drugs can be anchored to the biotinylated vasculature through avidin without being flushed away by blood flows. No apparent adverse effect was found in the functions of biotinylated kidneys. We propose that this drug delivery system is feasible for the treatment of some pathological conditions of blood vessels such as microvascular proliferation in malignant tumors and for continuous drug delivery in certain target organs. PMID- 11757780 TI - In vitro characterization of human intact erythrocytes loaded by enalaprilat. AB - In vitro characteristics of the human erythrocytes loaded by enalaprilat have been evaluated. Erythrocytes obtained from a healthy volunteer were loaded by enalaprilat using the hypotonic preswelling method, and the loading parameters, drug-release kinetics, hematological indices, particle size distribution, scanning electron microscopy view, osmotic and turbulence fragilities, and deformability of the resulting carrier cells were determined along with the sham encapsulated and unloaded cells. Carrier erythrocytes, having acceptable loading parameters, released their drug content according to zero-order kinetics. Mean corpuscular hemoglobin and mean corpuscular hemoglobin content values of the cells decreased, particle size dispersion increased, the cells transformed to cup form, the erythrocytes became more fragile against osmotic pressure and turbulent flow, and, finally, the deformability of the cells decreased significantly upon drug loading. PMID- 11757781 TI - Prolonged blood circulation of methotrexate by modulation of liposomal composition. AB - Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX. PMID- 11757783 TI - Literature alerts. PMID- 11757782 TI - Biodistribution and gastrointestinal drug delivery of new lipidic multilamellar vesicles. AB - Encapsulation of therapeutic molecules in a new noncationic multilamellar vector (Spherulites), composed of phosphatidylcholine, cholesterol, and polyoxyethylene alcohol, is described here. Spherulites with entrapped drugs were prepared by shearing a phospholipidic lyotropic lamellar phase using a recently discovered method. The average size of these vesicles is approximately 300 nm. Our formulation did not show cytotoxicity to human cells and could be used as a drug delivery system. Our previous experiments showed that this new multilamellar vector is stable in many different buffers such as serum, acidic or basic buffers, and enzymatic buffers and may deliver drugs in vivo. We describe two ways of administration for drug delivery. The tissue biodistribution of radiolabeled Spherulites entrapping 125I protein A was studied after intravenous injection in Wistar rats using the major organs of the body. Approximately 70% of the radioactivity was found in the spleen 60 min after injection and about half this percentage was found in the liver. By 6 hr, only 52% remained in the spleen. The other tissues accumulated <30% of the dose throughout the duration of the study. On the other hand, oral administration of Spherulites, entrapping111 In NTA, in fasting rats showed a significant increase of radioactivity in blood. PMID- 11757784 TI - Phenylketonuria (PKU): screening and management. AB - OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding screening for, and management of. phenylketonuria (PKU). PARTICIPANTS: A non-Federal, non advocate, 14-member panel representing the fields of pediatrics, genetics, human development, public policy, nursing, molecular physiology, and including patient representatives. In addition, 19 experts in pediatrics, medical genetics, psychology, pediatric neurology, biochemical and molecular genetics, and gene therapy presented data to the panel and to a conference audience of more than 300. EVIDENCE: The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: Genetic testing for PKU has been in place for almost 40 years and has been very successful in the prevention of severe mental retardation in thousands of children and adults. Metabolic control is necessary across the lifespan of individuals with PKU. A comprehensive, multidisciplinary, integrated system is required for the delivery of care to individuals with PKU. Greatly needed are consistency and coordination among screening, treatment, data collection, and patient support programs. There should be equal access to culturally sensitive, age-appropriate treatment programs. Ethically sound, specific policies for storage, ownership, and use in future studies of archived samples remaining from PKU testing should be established. Research into the pathophysiology of PKU and relationship to genetic, neural, and behavioral variation is strongly encouraged. Uniform policies need to be established to remove from the individual and the family financial barriers to the acquisition of medical foods and modified low-protein foods, as well as to provide access to support services required to maintain metabolic control in individuals with PKU. Research on nondietary alternatives to treatment of PKU is strongly encouraged. To achieve optimal statistical power, as well as cross cultural applicability, it will be beneficial to use data acquired via national and international collaboration. PMID- 11757785 TI - PIV-3 vaccine National Institutes of Health/Aviron. AB - Wyeth-Lederle, Aviron and NIH are developing a live intranasal parainfluenza virus (PIV) type 3 vaccine (cp45 vaccine). The vaccine is in phase II/III trials with Aviron [411386], and phase I trials with Wyeth-Lederle [408940]. It consists of a temperature-sensitive PIV-3 virus attenuated with an imported L gene mutation. This addition renders the virus 5-fold more restricted for replication in the respiratory tract of chimpanzees and also more temperature-sensitive [336999]. PMID- 11757786 TI - Rotavirus vaccine AVANT/GlaxoSmithKline. AB - AVANT Immunotherapeutics (formerly Virus Research Institute) and GlaxoSmithKline are developing a live oral rotavirus vaccine with potential to elicit a broadly protective immune response against the most prevalent strains of rotavirus. Following successful completion of a phase II clinical efficacy trial in June 1999, SmithKline Beecham (now GlaxoSmithKline) assumed responsibility for all subsequent clinical and other development activities [328635], [333677]. Following a licensing agreement, the vaccine was refined and renamed RIX-4414 [371713]. In May 2000, AVANT reported the results of a second-year surveillance extension of the phase II study. The results suggested that AVANT's two-dose oral rotavirus vaccine should be helpful in preventing rotavirus gastroenteritis (RGE) disease in young children for at least two years following administration [365202]. In March 2000, SmithKline Beecham reported that it had initiated phase I/II bridging studies in Europe and the company planned to start phase III safety and efficacy studies in 2001 after review with the health authorities [358963]. In October 2000, Dain Rauscher Wessels stated that an estimated market penetration of 30 to 40% suggested potential sales in excess of US $500 million pa. As a result, the analysts also estimated that incremental revenues to AVANT could be over US $50 million pa [411122]. PMID- 11757787 TI - Helivax Antex Biologics. AB - Antex Biologics is developing an oral vaccine against Helicobacter pylori infection as a potential treatment and prophylaxis for gastric ulcers. The vaccine incorporates a mucosal adjuvant and is in phase II trials [376332]. Enrollment for the trial was completed in September 2000 and results are expected in 2001 [382128]. In July 2000, Antex started a two-part phase Ib/II clinical trial of the vaccine. The first part was an open-label study to assess the general safety of the vaccine in uninfected and asymptomatic Helicobacter pylori infected individuals. The second part was an expanded placebo-controlled study to evaluate safety and immunogenicity of the vaccine. The vaccine was generally well tolerated and it generated an immune response in both infected and non-infected individuals [312681]. PMID- 11757788 TI - Anti-inflammatory approaches to the treatment of cystic fibrosis lung disease: past, present and future. AB - Inflammation has been increasingly recognized as a major factor in the pathogenesis of cystic fibrosis (CF) lung disease. The use of anti-inflammatory medications to slow pulmonary deterioration has been the focus of much research over the past two decades. Oral corticosteroids are effective, but are associated with significant adverse effects when used long-term. Inhaled corticosteroids are being studied as an alternative to systemic steroids. High-dose ibuprofen has also been shown to be of benefit in CF patients but has not been widely used. A variety of other non-specific anti-inflammatory agents, as well as antioxidants and antiproteinases, have been evaluated or are currently under investigation for use in CF. At present, the anti-inflammatory therapies used to treat CF lung disease are limited. There is hope that agents being evaluated in ongoing clinical trials will prove more effective than those already tested and that future research will provide additional anti-inflammatory therapies for CF airway disease. PMID- 11757789 TI - Targeting selectins for the treatment of respiratory diseases. AB - Inhibition of selectin function is expected to aid in the management of diseases characterized by aberrant or chronic inflammation, as in asthma and chronic obstructive pulmonary disease (COPD). Selectin-mediated adhesion of leukocytes to the vascular endothelium is a critical early event in the initiation of the inflammatory response, making it a good target for therapeutic intervention. Many approaches to modulating selectin function have been explored, including competitive inhibition, altering cell-surface expression and inducing shedding/cleavage from the cell surface; however, clinical success has been elusive. PMID- 11757790 TI - CpG oligodeoxynucleotides in asthma. AB - Asthma is a major health problem, of which the prevalence and severity are increasing, particularly in industrialized nations. One hypothesis for this is that diminished exposure to childhood infections in modern society has led to decreased Th1-type inflammation. Reduced Th1 responses may lead to enhanced Th2 type inflammation, important in promoting asthma and allergic disease. The most common current treatment for asthma is corticosteroids; while these agents inhibit the function of inflammatory cells, they are ineffective in altering the initial Th2-type response to allergen in a sensitized individual. A novel therapeutic approach, recently reported in the preclinical setting, is the use of oligodeoxynucleotides (ODNs), which contain unmethylated motifs centered on CG dinucleotides. These CpG ODNs potently induce Th1 cytokines and suppress Th2 cytokines, and can prevent manifestations of asthma in animal models. These agents have the potential to reverse Th2-type responses to allergens and thus restore balance to the immune system. Clinical trials are ongoing. PMID- 11757791 TI - Nepadutant Menarini Richerche. AB - Menarini Richerche is developing nepadutant, an NK2 antagonist, for the potential treatment of asthma and irritable bowel syndrome. The compound is in phase IIa trials in Belgium and Sweden for both these indications [359518]. PMID- 11757792 TI - New pharmacological strategies for the treatment of heart failure. AB - Heart failure still carries a high morbidity and mortality, necessitating new approaches for its management. Greater understanding of the pathophysiology of heart failure has opened the way for novel therapeutic approaches, including analogs of natriuretic peptides and drugs that modulate endothelin, cytokine release and endothelial vasoconstriction. Other drugs are undergoing laboratory and clinical trials that will eventually supersede or complement less optimal heart failure treatments. Clinical trials will ascertain if these new strategies in the treatment of heart failure will ultimately be successful in the management of these patients. PMID- 11757793 TI - BNP in decompensated heart failure: diagnostic, prognostic and therapeutic potential. AB - B-type or brain natriuretic peptide (BNP) is a balanced vasodilator with no inotropic nor chronotropic properties. Plasma levels can be used in diagnosis and prognosis of patients with heart failure, hypertension, myocardial infarction, right ventricular dysfunction and cor pulmonale. Intravenous therapy with BNP (nesiritide) in nearly 1000 patients demonstrated significant dose-dependent reductions in pulmonary capillary wedge pressure and systemic vascular resistance, as well as increased cardiac index. Compared to dobutamine, it is not pro-arrhythmic and has no effect on heart rate. Compared to standard therapy, it improves dyspnea by 3 h of therapy and leads to fewer headaches and arrhythmias than the commonly used intravenous agents nitroglycerin and dobutamine, respectively. Current research suggests an important role for use of nesiritide in the treatment of decompensated heart failure. PMID- 11757794 TI - JTV-519 Japan Tobacco. AB - Japan Tobacco is developing the mixed action ion channel blocker, JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998; phase II trials started in the fourth quarter of 1998 for the potential treatment of myocardial infarction [320195]. Studies have shown that JTV-519 has a strong cardioprotective effect against catecholamine-induced myocardial injury and against ischemia/reperfusion injury [316749]. In experimental myofibrillar overcontraction models, it demonstrated greater cardioprotectant effects than propranolol, verapamil and diltiazem [171668]. PMID- 11757795 TI - Use of atypical antipsychotics in mood disorders. AB - Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction. PMID- 11757796 TI - SB-277011 GlaxoSmithKline. AB - It is presumed that GlaxoSmithKline has taken over from SmithKline Beecham in investigating the highly selective dopamine D3 antagonist SB-277011 and its analogs for the potential treatment of schizophrenia [284490] following the merger of Glaxo Wellcome and SmithKline Beecham in December 2000 [394715]. In June 2000, it was reported that novel 2,3,4,5-tetrahydro-1H-benzazepines and 2,3 dihydro-1H-isoindoles, including SB-277011, had shown high affinity and selectivity for the dopamine D3 receptor. All compounds were suggested to have further potential roles in the treatment of drug abuse and psychosis [372205]. In November 2000, data presented at the 30th Neuroscience meeting in New Orleans, LA, demonstrated that D3 receptor blockade with SB-277011 specifically altered neurochemical effects in the nucleus accumbens without the non-selective effects, such as catalepsy, seen with some other antagonists [390460]. PMID- 11757797 TI - Osanetant Sanofi-Synthelabo. AB - Osanetant is a neurokinin (NK3) receptor antagonist under development by Sanofi Synthelabo (formerly Sanofi) as a potential treatment for schizophrenia [328910]. Sanofi was originally investigating its potential use as a treatment for psychosis and anxiety [169511]. Following phase IIa clinical trials [307656], [328910], [359231], osanetant entered phase IIb development in February 2001 [409432]. Osanetant was the first potent and selective non-peptide antagonist described for the NK3 tachykinin receptor [176305]. It has a higher affinity for human and guinea pig NK3 receptors than for rat NK3 receptors [176305]. In October 1999, Lehman Brothers predicted that the probability of the product reaching the market was 10%, with a possible launch in 2003 and potential peak sales of US $200 million in 2011 [346267]. PMID- 11757798 TI - Immunotherapy for cancer: focusing on developing treatments rather than drugs. PMID- 11757799 TI - Immunization against tumor cell surface complement-regulatory proteins. AB - Complement is an enzymatic cascade that results in the release of pro inflammatory anaphylatoxins, C3b deposition and the assembly of the membrane attack complex (MAC), which results in cell lysis. Cells express complement regulatory proteins or inhibitors to protect themselves from bystander attack by complement. Expression of the complement-regulatory proteins CD55, CD46 and CD59 are deregulated in cancer with tumors showing loss of one or more inhibitors and strong overexpression of others. This results in tumors that are resistant to attack by complement and is a major limitation in the use of monoclonal antibodies as monotherapies. However, tumor sensitivity to complement can be restored by co-administration of antibodies that bind to the functional domains of complement-regulatory proteins. Overexpression of complement-regulatory proteins on tumors also makes them potential targets for cancer vaccines. However, these vaccines have to be carefully designed to induce immune responses that recognize inhibitors overexpressed on tumors and that do not detect the levels expressed by normal cells. A human anti-idiotypic antibody that mimics CD55 has been used successfully in over 200 colorectal cancer and osteosarcoma patients. 70% Of patients show CD55-specific immune responses with no associated toxicity. Similar vaccines targeting CD46 and CD59 would eliminate any cell overexpressing a complement inhibitor. Any remaining tumor cell or any tumor cell that loses complement-regulatory proteins in response to therapy would become highly susceptible to in situ complement deposition. In summary, targeting complement-regulatory proteins is a very attractive approach to tumor therapy, although great care must be taken in preventing normal tissue recognition as this could lead to uncontrolled complement deposition and massive cell lysis. PMID- 11757800 TI - Small-molecule cytokine inducers causing tumor necrosis. AB - The capillary networks of solid tumors are more permeable and less well organized than those of normal tissue. This review explores the hypothesis that these differences might be exploited as a selective antitumor strategy. Both high and low molecular weight compounds have been found to induce cytokines such as tumor necrosis factor (TNF) and to inhibit tumor blood flow in experimental tumors, with consequent induction of necrosis. Flavone acetic acid (FAA) and 5,6 dimethylxanthenone-4-acetic acid (DMXAA) are of particular interest. Accumulating evidence implicates the enzyme IkappaB kinase, which leads to the activation of the transcription factor, NFkappaB, as a target for these drugs. The downstream effects of FAA and DMXAA on the tumor microcirculation are complex, involving both direct and indirect effects on vascular endothelial cells. Induced changes in the shape and organization of vascular endothelial cells may lead to the activation of blood platelets and the release of 5-HT. Cytokines, 5-HT and nitric oxide (NO) released in response to FAA and DMXAA may induce a sustained increase in the permeability of tumor vascular cells, leading to cessation of blood flow and induction of tumor necrosis. Exploitation of this principle to clinical anticancer therapy represents an important challenge for the future. PMID- 11757801 TI - Leuvectin Vical Inc. AB - Vical's Leuvectin, a plasmid DNA expression vector encoding interleukin-2 (IL-2) complexed with a lipid delivery vehicle (DMRIE/DOPE)for intratumoral injection, is under development as a potential gene therapy for cancer. In 1997, it was in phase II trials for kidney and prostate cancer [249445], [270243]. In April 2001, the phase II trial in kidney cancer was discontinued, with a new phase II trial planned for this indication [406405]. In May 2001, prostate cancer trials were ongoing [409071]. By March 1999, testing for other indications had been suspended, with the company's priority being to work toward the most promising indications [316709]. In November 2000, it was announced that Vical has been issued US-06147055 for the use of gene-based, non-viral delivery of IL-2 for the treatment of cancer. The company was also issued US-05641665 covering the Leuvectin construct in 1997 [389677]. PMID- 11757802 TI - Diabetes mellitus and oral disease. AB - The oral complications of diabetes mellitus are generally considered to be no more than inevitable annoyances and, as such, have been the subject of relatively few scientific and clinical studies. This review highlights both the known correlations between oral disease and diabetes mellitus, such as those involving supporting tissues and oral mucosa, and those that are still a matter of debate, such as dental caries. In all cases, we carefully analyzed the pathogenesis of the disorder with a view to establishing a possible therapeutic approach, an aspect that currently appears to be overlooked. In view of the fact that the treatment of certain oral conditions, in particular periodontal disease, has been reported to improve metabolic control in diabetic patients, we conclude that diabetes mellitus-related oral diseases deserve adequate recognition and further investigation. PMID- 11757803 TI - The basal energy expenditure of female athletes vs. sedentary women as related to their family history of type 2 diabetes. AB - The purpose of this study was to investigate the basal metabolic rate (BMR) in 16 professional sportswomen (soccer players) versus 15 sedentary women, as related to the presence (FH+) or absence (FH-) of a family history of type 2 diabetes. The sportswomen, in toto, had a significantly higher BMR than expected from predictive equations (+14.92%). However, the difference was limited only to FH- sportswomen (+18.66%, p<0.0005). FH- sportswomen showed a significantly higher measured BMR than FH+ sportswomen (p<0.005), and FH+ (p=0.058) and than FH- (p<0.05) sedentary women. There were no other significant differences relative to physical, metabolic and plasmatic data between the groups. The sportswomen with familiarity to type 2 diabetes had a BMR lower than that of FH- sportswomen, and similar to that of sedentary sedentary women. It appears that FH+ sportswomen have a "sub-clinical metabolic inertia", representing a precocious signal in young diabetes-prone subjects, despite the modifications induced from activity on their body composition (increased FFM, even though marginally significant). PMID- 11757804 TI - Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat. AB - Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/ 2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities. PMID- 11757805 TI - Bacterial pneumonia: comparison between diabetics and non-diabetics. AB - To determine the causative organisms, antimicrobial susceptibility, and outcome of community- and hospital-acquired pneumonia in diabetics and to compare this with non-diabetics, sputum cultures done at King Abdulaziz University Hospital in the period between January 1998 and December 1999 were reviewed. A total of 354 cases were studied, of which 125 (35%) were diabetics. Diabetic patients were older with a male predominance compared to non-diabetics. H. influenza was the commonest pathogen in community-acquired pneumonia (CAP) in both diabetics and non-diabetics, but there was a predominance of Staphylococcus aureus in diabetics compared to non-diabetics. Gram-negative bacilli were the commonest pathogens in hospital-acquired pneumonia (HAP) in both diabetics and non-diabetics. Ampicillin, co-amoxyclav, flouroquinolones, second-generation cephalosporins and erythromycin were used empirically in CAP while aminoglycosides, fluoroquinolones and imipenem were used in HAP in both diabetics and non-diabetics. No significant difference in mortality was found between diabetics and non-diabetics, for either CAP or HAP. PMID- 11757806 TI - DAPIT, a novel protein down-regulated in insulin-sensitive tissues in streptozotocin-induced diabetes. AB - We have identified a novel gene product differentially expressed in skeletal muscle in a rat diabetes model induced by streptozotocin. Northern blot analysis showed expression in all studied tissues and a marked down-regulation in insulin sensitive tissues (skeletal muscle, myocardium) but not in insulin-insensitive brain. cDNA sequence analysis revealed an open reading frame (ORF) of 58 aminoacids, containing one putative transmembrane domain. We designated this protein DAPIT (diabetes-associated protein in insulin-sensitive tissues). Database searches discovered several human, rat, mouse, rabbit, bovine, equine, porcine, Fugu and Xenopus ESTs with significant homology in the ORF. The aminoacid sequence of DAPIT is similar to that of a putative protein of Drosophila melanogaster and to a cAMP-generating peptide isolated from the flesh fly Neobellieria bullata. We propose that DAPIT is a novel protein that is highly conserved in vertebrates and insects. PMID- 11757807 TI - The parental phenotype of diabetes, but not of essential hypertension, is linked to the development of metabolic syndrome in Mexican individuals. AB - Studies on the role of parental history on the risk of developing metabolic syndrome (MS) show inconsistent data that may depend on misclassification of the parental history. Confirming carefully the parental phenotype (PF) of type 2 diabetes mellitus (DM) and essential hypertension (EH) of participants' parents, we determined the relationship between PF of either DM or EH and the risk of developing MS in Mexican individuals. A case-control study of 210 subjects randomly recruited from Durango, Mexico was carried out. Subjects with MS (cases) were compared with a control group of subjects without MS matched by age and gender. MS was defined by the presence of two or more of the following: fasting glucose > or =7.0 mmol/l; blood pressure > or =160/90 mmHg; fasting triglycerides > or =1.7 mmol/l and/or HDL-cholesterol <1.0 mmol/l; and obesity (body mass index > or =30 kg/m2 and/or waist-to-hip ratio > or =0.85). The PF of DM and EH was confirmed by direct clinical examination and/or review of certificates of death of each of the participants' parents. Incomplete or unclear data about PH were exclusion criteria. Multivariate analysis showed that PF of DM without EH (odds ratio (OR) 2.6; 95% CI, 1.3-7.8, p=0.044) and PF of both DM and EH (OR, 3.1; 95% CI, 1.5-9.1, p=0.0001), but not the PF of EH without DM are independent predictors for developing MS in Mexican individuals. In the offspring generation of Mexican subjects, the PF of DM seems to increase the risk of developing MS, whereas PF of EH does not. PMID- 11757808 TI - Prediction of lean body mass from multifrequency segmental impedance: influence of adiposity. AB - The aim of the study was to determine the influence of adiposity on the relationship between bioelectrical impedance (BIA) measurements of body segments and estimation of body composition by dual-energy X-ray absorptiometry (DXA). Multiple frequencies of whole body and segmental impedances were measured in 68 normal-weight and obese subjects (46 women and 22 men), mean age 37.2+/-14.8 years (range, 18-69). Total and appendicular lean body mass (LBM) assessed by DXA correlated significantly with total and segmental impedance values adjusted for stature in both obese and normal-weight subjects. Best fitting equations for the prediction of appendicular LBM from segmental impedance measurements were derived for the arm and leg with and without the inclusion of adiposity (the percentage of body fat measured by DXA) in the regression models. Best prediction was obtained at low frequency for the arm and high frequency for the leg. Adiposity appears to significantly influence the prediction of leg LBM by BIA. These preliminary observations need further validation to provide an accurate assessment of appendicular LBM assessment by BIA. PMID- 11757809 TI - Static perimetry and diabetic retinopathy: a long-term follow-up. AB - In order to evaluate if central static perimetry is useful to identify patients at risk of developing diabetic retinopathy, 60 (27 male, 33 female) adolescents and young adults (mean age, 15.9 years) with insulin-dependent diabetes mellitus were studied prospectively. No patient showed fluorescein angiographic signs of retinopathy initially. The patients were evaluated at the beginning of the study and after 8 years. At the beginning of the study, mean defect in the population was -2.34 dB as determined by perimetry; no patient showed significant impairment of foveal threshold (mean, 33.17 dB). After 8 years of follow-up, 7 patients had developed fluorangiographic signs of retinopathy. Life-table analysis showed that the overall probability of retinopathy development was significantly higher in subgroups of patients with mean sensitivity in areas 2 and 3 below the cutoff. These results suggest that central static perimetry is a useful tool in predicting the development of retinopathy in children with insulin-dependent diabetes mellitus who do not have fluorescein angiographic signs of retinopathy. This tool can help the physician to identify those patients at risk of developing fluorangiographic signs of retinopathy. PMID- 11757810 TI - Imaging of neuronal activity in the gut. AB - Over the past few years, several groups have used voltage-sensitive dyes or calcium-indicator dyes to optically monitor the activity of several enteric neurons simultaneously. Some of the initial practical problems have been solved and these studies have successfully shown the spread of electrical activation within the enteric neuronal circuitry in cultures and in ex vivo specimens. The basic mechanisms underlying voltage-sensitive dye or calcium-indicator signals and their relation to changes in membrane potential need further investigation. Application of these techniques will provide more insight into neuronal interaction and spread of activation. The ability to simultaneously record activity in other cells in the same focal plane offers the potential to investigate how the integrated neuronal circuits are linked to effector cells in their close neighbourhood. Progress in optical imaging of enteric neuronal activity should ultimately lead to a better knowledge of gastrointestinal physiology and pathophysiology. PMID- 11757811 TI - Enhancement of intestinal growth and repair by growth factors. AB - Recently, glucagon-like peptide 2 has emerged as a potent stimulator of epithelial growth, joining insulin-like growth factor I, hepatocyte growth factor and keratinocyte growth factor as potential treatment modalities for intestinal disorders associated with loss of mucosal mass, such as short bowel syndrome. Investigations into other members of the expanded epidermal growth factor peptide family, the development of more potent peptide analogues, and advances in the development of enterally administered bioactive growth factor formulations further expands the repertoire of epithelial growth factors applicable to conditions associated with epithelial insufficiency. PMID- 11757812 TI - Protease-activated receptors: how proteases signal to cells. AB - Certain proteases from the circulation, mast cells and elsewhere signal directly to cells by cleaving protease-activated receptors (PARs), members of a new subfamily of G-protein-coupled receptor. Cleavage exposes a tethered ligand domain that binds to and activates the cleaved receptors. Advances in the past year have improved our understanding of the molecular mechanisms of this signaling and how it is switched off. It is now recognized that PARs play important roles in 'emergency situations' - such as trauma, when there is generation or release of proteases - and are involved in coagulation, inflammation, pain, healing and protection. Selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases. PMID- 11757813 TI - Tachykinin receptors in the gut: physiological and pathological implications. AB - The tachykinins substance P and neurokinin A participate in the regulation of gastrointestinal motility, secretion, vascular permeability and pain sensitivity. Advances made during the past two years corroborate a causal involvement of tachykinins in inflammation-induced disturbances of gut function, such as dysmotility, secretory diarrhoea, oedema and hyperalgesia. It would therefore appear that tachykinin receptors, which in the digestive system are expressed in a cell-specific manner, represent attractive targets for novel therapeutics in gastroenterology. PMID- 11757814 TI - Glutamate in the enteric nervous system. AB - Several lines of evidence indicate a role for glutamate in the regulation of gut motility and secretion; however, the receptor subtypes that mediate the effects of this amino acid are still incompletely understood. There has, however, been recent progress in pharmacological characterization of enteric glutamate receptor subtypes. In the past two years, investigators have demonstrated that in addition to ionotropic glutamate receptors, the enteric nervous system contains functional group I metabotropic glutamate receptors that appear to participate in enteric reflexes. This opens up an entirely new arena in which to study the roles of glutamate in gut function and presents potential new target sites for drug development. PMID- 11757815 TI - The gastrointestinal pharmacology of cannabinoids. AB - The digestive tract contains endogenous cannabinoids (anandamide and 2 arachidonylglycerol) and cannabinoid CB1 receptors can be found on myenteric and submucosal nerves. Activation of CB1 receptors inhibits gastrointestinal motility, intestinal secretion and gastric acid secretion. The enteric location of CB1 receptors could provide new strategies for the management of gut disorders. PMID- 11757816 TI - Control of migrating motor activity in the colon. AB - One of the most significant developments in our approach to studying gastrointestinal motility over the past few years has been in the advent of genetic manipulation and the development of knockout animals. This means that it is possible to study motility patterns of specific regions of the gastrointestinal tract in which the development or synthesis of particular neurotransmitter substances or receptors has been prevented. The mouse has emerged as the model species for investigating the effects that genetic knockouts may have on gastrointestinal motility; therefore, an understanding of the mechanisms underlying the control of motility patterns of unaffected mice is crucial before we can apply this knowledge to knockout models. Major advances have been made in the past few years regarding the mechanisms underlying the generation of migrating motor complexes in the large bowel, particularly in the mouse colon. PMID- 11757817 TI - Estrogen receptors and endocrine diseases: lessons from estrogen receptor knockout mice. AB - The estrogen receptors ERalpha and ERbeta are the main mediators of estrogen action and estrogens play an important role in a variety of aspects of physiology besides their well acknowledged function in reproduction. In vivo and in vitro studies indicate that the estrogen receptors are mechanistically implicated in endocrine-related diseases. Recent studies with estrogen receptor knockout mice have helped to unravel the role of the estrogen receptors in brain degeneration, osteoporosis, cardiovascular diseases and obesity. PMID- 11757818 TI - Genetic targets for the treatment of pituitary adenomas: focus on the pituitary tumor transforming gene. AB - The pituitary tumor transforming gene (PTTG) has been identified as a key protein in mitotic regulation. The hypothesis that PTTG overexpression results in genetic instability has been strengthened by the recent observation of inappropriate and aneuploid cell division in cell lines expressing high levels of PTTG. PTTG transactivates the oncogene c-myc, which in turn may influence cell growth. A direct link between PTTG, basic fibroblast growth factor and angiogenesis has been demonstrated. PMID- 11757819 TI - Thyroid disease and its treatment: short-term and long-term cardiovascular consequences. AB - Thyroid hormones exert important effects on the cardiovascular system, including effects on cardiac systolic and diastolic function, peripheral vascular resistance and arrhythmogenesis. Hyperthyroidism and hypothyroidism often cause opposing effects on cardiovascular physiology in the short term. Increasing evidence suggests that long-term vascular morbidity and mortality occurs in both overt and subclinical thyroid disease. PMID- 11757820 TI - Control of growth and development of the feto-placental unit. AB - Classical gene targeting has identified many genes important for fetal and placental development. Null mutation of these genes may lead to fetal growth restriction, malformation or embryonic death. Growth restriction of epigenetic basis can predispose to adult-onset diseases. The mechanisms underlying this process, termed 'fetal programming', are beginning to be understood. PMID- 11757821 TI - Growth and development of the islets of Langerhans: implications for the treatment of diabetes mellitus. AB - In the past couple of years a number of major breakthroughs have been made in understanding the developmental biology of the islets of Langerhans. These include the involvement of the hedgehog signalling pathway in defining the region of the gut endoderm that will develop into the pancreas; the discovery that the transcription factor neurogenin3 and the Delta/Notch signalling pathway control endocrine cell differentiation through a lateral inhibition mechanism; and that alpha and beta cells are derived from an islet progenitor cell and follow independent lineage pathways rather than arising from a common mutihormonal progenitor cell as previously thought. This knowledge had been used in strategies to provide a replenishable supply of insulin-secreting cells for the treatment of diabetes mellitus. Thus, islet progenitor cells in adult pancreatic ducts or in isolated islets of Langerhans have been induced to grow in culture and their endocrine-like properties have been characterised. A proliferating beta-like cell line has been derived from tissue removed from a child with persistent hyperinsulinaemic hypoglycaemia of infancy and been engineered in culture to secrete insulin in response to glucose. And finally, embryonic stem cells have been shown to adopt islet-like characteristics under defined culture conditions. PMID- 11757823 TI - Leptin and the control of obesity. AB - Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Its main physiological role may be to coordinate the metabolic, endocrine and behavioural responses to starvation. Recent work has identified many factors that regulate leptin production and secretion, including nutrients, hormones and the sympathetic nervous system. Some characteristics of leptin responsive hypothalamic neurones have now been defined. Other roles for leptin in gut and immune regulation and in foetal development have been proposed. Leptin itself seems ineffective in treating most human obesity, but alternative means of activating appetite-regulatory pathways downstream of leptin are targets for future pharmacological approaches to aid weight loss. PMID- 11757822 TI - Hypothalamic peptides as drug targets for obesity. AB - The importance of the melanocortin system in obesity has been confirmed by the recent discovery of mutations in the melanocortin MC4 receptor in morbidly obese patients and the finding that intranasal administration of a fragment of melanocortin decreases body fat in humans. Transgenic mice overexpressing melanin concentrating hormone (MCH) are obese and a second MCH receptor has been identified. In addition, ghrelin, endocannabinoids and glucagon-like peptide 2 have been identified as potentially important central regulators of food intake. PMID- 11757824 TI - Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. AB - Over the past year, human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor (MIF) in a number of diseases that had originally been studied in animals. In addition to sepsis, rheumatoid arthritis, glomerulonephritis and inflammatory lung disease, elevated MIF levels have been described in patients suffering from ulcerative colitis, inflammatory neurological diseases and cancer. Cellular studies indicate that in addition to macrophages, MIF affects the activities of CD4+ and CD8+ T cells, natural killer cells, fibroblasts and endothelial cells, actions that may explain the contribution of MIF to inflammatory diseases and cancer. Molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins (Jab1, PAG and p53) that control cellular growth and proliferation; however, how interactions with these proteins fit into a general scheme to explain MIF's biological activity has not been elucidated. The three-dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF-associated diseases, they may provide good targets for therapeutic intervention. PMID- 11757825 TI - A summary of the 2000 update of the NKF-K/DOQI clinical practice guidelines on peritoneal dialysis adequacy. PMID- 11757826 TI - Relationship between adequacy of dialysis and nutritional status, and their impact on patient survival on CAPD in Hong Kong. AB - OBJECTIVE: Superior patient survival on continuous ambulatory peritoneal dialysis (CAPD) with 3 x 2-L exchanges has been reported from Hong Kong. This study examined the relationship between indices of dialysis adequacy and nutrition and patient survival on CAPD in Hong Kong. DESIGN: A cross-sectional study on prevalent CAPD patients. Patients were assessed for indices of dialysis adequacy and nutritional status with a composite nutritional index (CNI). Patients were then followed for 24 months. Survival data were analyzed according to adequacy indices and nutritional status. SETTING: All prevalent CAPD patients in nine dialysis centers in Hong Kong as of 1 April 1996. MAIN OUTCOME MEASURE: Mortality. RESULTS: 937 patients were assessed: 68.2% were using 3 x 2-L exchanges per day; mean age was 54.6 +/- 13 years. Mean total Kt/V was 1.83 +/- 0.42 and total creatinine clearance was 55.6 +/- 19.5 L/week/1.73 m2. 19% of patients were moderately to severely malnourished according to the CNI. There was no significant correlation between indices of adequacy and serum albumin or CNI. The 1- and 2-year patient survival from the time of assessment was 90.9% and 79.8%. There was a trend toward better survival in patients with Kt/V greater than 2.0, but it was not statistically significant. Peritoneal Kt/V did not impact survival in anuric patients. Malnourished patients had poorer survival than patients who were better nourished (p = 0.0259). After adjusting for age and diabetes, CNI was predictive of mortality but Kt/V and creatinine clearance were not. CONCLUSIONS: This study demonstrates the importance of nutritional status over adequacy indices in predicting patient survival. There was a lack of correlation between nutritional status and conventional indices of dialysis adequacy. PMID- 11757827 TI - Effects of long-term erythropoietin therapy on the hypothalamo-pituitary testicular axis in male CAPD patients. AB - OBJECTIVE: Gonadal dysfunction has been recognized for a long time in uremic male patients. The present study assesses the hypothalamo-pituitary-testicular axis and growth hormone status in male continuous ambulatory peritoneal dialysis (CAPD) patients, before and after recombinant human erythropoietin (rHuEPO) therapy. DESIGN: Single-center prospective study. SUBJECTS: Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were included in the study. All patients were on CAPD therapy and none had received rHuEPO treatment previously. MAIN OUTCOME MEASURES: Blood samples were collected between 0800 and 0900 hr from all patients for the determination of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A luteinizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 microg intravenous as a bolus injection. Blood for FSH, LH, and GH determinations was drawn every 30 minutes during the 3-hour test period. Human chorionic gonadotropin (hCG) test was performed after 48 hours. After estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total and free testosterone levels were measured in blood samples collected before and 48 hours after two injections of hCG. After improvement in anemia with exogenous rHuEPO, LH-RH and hCG tests were repeated. RESULTS: Baseline FSH concentrations before and after rHuEPO treatment were slightly higher in CAPD patients than in healthy volunteers (p = 0.85 and p = 0.70, respectively). Areas-under-the-curve (AUCs) for FSH secretion before and after rHuEPO treatment were also slightly higher in patients than in healthy volunteers (p = 1.00 and p = 0.75, respectively). The pretreatment basal LH levels in patients were significantly higher than in controls (p < 0.001). After the improvement in anemia with rHuEPO, serum LH levels declined significantly (p < 0.05). The AUCs for LH secretion before and after rHuEPO treatment were significantly higher in patients than in controls (p < 0.05). All patients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in healthy subjects (p < 0.001) before rHuEPO treatment. After treatment with rHuEPO, basal GH levels declined but did not normalize, and baseline levels of free testosterone increased significantly (p < 0.05). CONCLUSION: Anemic uremic male patients on CAPD have normal levels of testosterone with normal response to hCG administration, elevated basal levels of GH, and elevated basal levels of LH, with exaggerated response to LH-RH administration. Improvement in anemia with rHuEPO reduced the basal levels of LH and GH, but exaggerated the LH response; paradoxical GH response to LH-RH administration persisted. These results indicate a defect at the level of the hypothalamus and pituitary gland in uremic male patients undergoing CAPD, and that the improvement in anemia with rHuEPO partially restores some of these endocrine abnormalities. PMID- 11757828 TI - Clinical benefits and tolerability of increased fill volumes in Japanese peritoneal dialysis patients. AB - BACKGROUND: Increasing fill volume is an effective means of improving clearances in patients on peritoneal dialysis (PD). Since Japanese PD patients are physically smaller than their Western counterparts, there is some concern that PD patients in Japan may be unable to tolerate larger fill volumes. OBJECTIVE: To determine patient tolerance and changes in solute clearance and net ultrafiltration resulting from increased fill volumes in Japanese patients on PD. DESIGN: Prospective double-blind study, randomizing patients to three different fill volumes (2.5% dextrose solution: 1.5 L, 2.0 L, or 2.5 L) administered in random order on three different occasions separated by 1 week. RESULTS: Twenty one patients with a mean age of 55.4 +/- 2.1 years and a mean body surface area of 1.66 +/- 0.03 m2 were studied. On a scale of 0 to 10, patients' mean discomfort scores were 2.14 +/- 0.59, 3.48 +/- 0.54, and 3.81 +/- 0.63 (p = 0.047) at the end of the 1.5-L, 2.0-L, and 2.5-L dwells, respectively. There were no reports of cramps or shortness of breath with any fill volume. Patients were able to correctly guess the actual fill volume for only 34 of the 63 total exchanges (54.0%). Increasing fill volume resulted in an incremental improvement in peritoneal creatinine clearance, from 3.74 +/- 0.16 to 4.49 +/- 0.21 (p < 0.001, 2.0 L vs 1.5 L) to 5.12 +/- 0.20 mL/minute (p< 0.001, 2.5 L vs 2.0 L) for 1.5-L, 2.0-L, and 2.5-L dwells, respectively. Peritoneal urea clearance also increased significantly, from 5.65 +/- 0.13 to 7.04 +/- 0.17 (p < 0.001, 2.0 L vs 1.5 L) and 8.16 +/- 0.29 mL/minute (p < 0.001, 2.5 L vs 2.0 L), with incremental increases in fill volume. Similarly, net ultrafiltration in a 4-hour dwell increased significantly with fill volume, from 255.24 +/- 24 mL with 1.5 L, to 356 +/- 24 (p < 0.004, 2.0 L vs 1.5 L) and 392 +/- 29 mL (p < 0.086, 2.5 L vs 2.0 L) in patients receiving 2.0 L and 2.5 L, respectively. CONCLUSION: Increasing the fill volume results in improvement in solute clearance and net ultrafiltration in Japanese PD patients, with minimal increase in patient discomfort. A large percentage of patients were unable to identify the actual fill volume. PMID- 11757829 TI - Dissociation between clearances of small and middle molecules in incremental peritoneal dialysis. AB - OBJECTIVE: To evaluate the peritoneal clearance of middle molecules in comparison with the peritoneal clearance of small molecules in incremental peritoneal dialysis (PD). STUDY DESIGN: Peritoneal clearances of creatinine and beta2 microgloblulin (B2M) were compared in 57 continuous ambulatory PD patients on full dose of 4 exchanges, and 54 incremental PD patients with 2 or 3 exchanges over 24 hours. Clearances were also compared when there were changes in the PD regimen, such as in the number of exchanges and the duration of the dwell time. SETTING: Tertiary-care university hospital. RESULTS: Peritoneal creatinine clearance increased almost linearly with the increase in the number of exchanges. In contrast, peritoneal clearance of B2M was 9.1 +/- 3.6 L/week, 8.8 +/- 4.4 L/week, and 7.9 +/- 2.5 L/week with 2,3, and 4 exchanges, respectively, per day, amounts that were not different from each other. Peritoneal clearance of B2M did not change when there was an increase in the number of dialysate exchanges from 2 to 3 and from 3 to 4 over a period of 24 hours; whereas the peritoneal clearance of creatinine increased. Peritoneal clearance of B2M almost doubled, from 5.4 +/- 2.7 L/week with 2 exchanges over 12 hours per day, to 9.5 +/- 4.4 L/week with the same 2 exchanges over 24 hours. The creatinine clearance did not change. CONCLUSION: In contrast to peritoneal clearance of small molecules, such as creatinine, which was dependent on the number of dialysate exchanges, peritoneal clearance of middle molecules, such as B2M, depended mainly on the total dwell hours of PD and not on the number of exchanges of peritoneal dialysate in incremental PD. This might be another advantage of incremental PD, since peritoneal clearance of middle molecules in incremental PD over 24 hours can be comparable to that in full dose PD. PMID- 11757830 TI - Timing of peritoneal dialysis catheter removal after pediatric renal transplantation. AB - BACKGROUND: A peritoneal dialysis (PD) catheter is in place at the time of kidney transplantation in children receiving PD. Removal of the catheter eliminates the risk of catheter-related infections. However, the patient benefits from leaving the catheter in place if dialysis is necessary posttransplantation. There is currently no consensus on the proper timing of PD catheter removal after kidney transplantation in children. OBJECTIVE: To identify the risks and benefits of an in-dwelling PD catheter after renal transplantation in children. DESIGN: Retrospective single-center study of infectious complications and posttransplantation PD catheter use in 31 renal transplantations in 26 children. RESULTS: Peritoneal dialysis catheters were used postoperatively in 13 of the 31 transplantations. In 12 instances the catheter was needed during the first month after transplantation, and 2 of the patients involved did not have a catheter in place when needed. Six catheter-related infections occurred in 5 patients posttransplantation, with only 1 infection taking place within 1 month after transplantation. CONCLUSION: Our data suggest that the need for catheter use occurs predominantly during the first month, while infectious complications usually happen later. This strongly suggests that PD catheters should not be removed until approximately 1 month after kidney transplantation. PMID- 11757831 TI - Effect of preventing Staphylococcus aureus carriage on rates of peritoneal catheter-related staphylococcal infections. Literature synthesis. AB - OBJECTIVE: To determine whether specific preventive measures reduce the rate of peritoneal catheter-related infections and peritoneal catheter loss due to Staphylococcus aureus. DESIGN: Structured literature synthesis. METHODS: Relevant studies were identified by MEDLINE search, from personal files, and from the reference lists of retrieved articles. We analyzed English-language studies on treatment targeted at S. aureus, with at least 10 subjects and at least 3 months of follow-up, and data on staphylococcal peritoneal dialysis catheter infections. We excluded noncontrolled studies. Two investigators abstracted data using a structured form. RESULTS: We evaluated six studies with concurrent controls and eight studies with historical controls. In one randomized, placebo-controlled, blinded study, periodic nasal mupirocin ointment reduced the rate of staphylococcal exit-site infection from 0.42 to 0.12 episodes/patient-year (p = 0.006), but had no effect on the rates of staphylococcal tunnel infection, peritonitis, or catheter loss. In one randomized study without placebo control, periodic oral rifampin reduced the rate of staphylococcal exit-site infection from 0.65 to 0.22 epi/pt-yr (p = 0.011), but had no effect on the rate of staphylococcal peritonitis. In another nonblinded, randomized, controlled study, the use of either rifampin or mupirocin was associated with low rates of staphylococcal catheter infections and catheter loss. In one study with historical controls, the rate of staphylococcal exit-site infection and peritonitis was lower after oral rifampin prophylaxis. In seven other studies comparing nasal or exit-site mupirocin to historical controls, the rate of staphylococcal exit-site infection decreased from 0.17 to 0.05 epi/pt-yr, the rate of staphylococcal peritonitis decreased from 0.18 to 0.06 epi/pt-yr, and the rate of catheter loss decreased from 0.09 to 0.05 epi/pt-yr during the mupirocin period. CONCLUSION: The literature provides strong evidence that staphylococcal carriage prophylaxis using either oral rifampin or mupirocin ointment in the nares or exit site reduces significantly the rate of exit-site infection due to Staphylococcus aureus. Weaker evidence based on studies with historical controls suggests that rifampin or mupirocin prophylaxis also reduces the rate of staphylococcal peritonitis and peritoneal catheter loss. Studies with a stronger level of evidence are needed to verify this last point. PMID- 11757832 TI - Intraperitoneal ciprofloxacin and rifampicin versus cephradine as initial treatment of (C)APD-related peritonitis: a prospective randomized multicenter comparison (CIPPER trial). AB - OBJECTIVE: The initial treatment of peritonitis has evolved from single-agent to combination regimens. The initial response rates improved with these newer regimens but relapsing peritonitis continues to occur. For biofilm-embedded or intracellularly sequestrated bacteria, a combination of intracellularly- and biofilm-active agents such as ciprofloxacin and rifampicin might be beneficial. Many Dutch centers continue to use cephradine as initial treatment, claiming clinically adequate responses with this regimen. We compared the impact of these two regimens on outcome in patients who developed a new episode of peritonitis. DESIGN: Prospective randomized open trial. SETTING: Multicenter study including 14 Dutch dialysis units. PATIENTS AND INTERVENTIONS: From October 1996 to October 1999, 367 patients from 14 centers were randomized to be treated with ciprofloxacin + rifampicin (CR; each 50 mg/L) or cephradine (C; 250 mg/L) in case of peritonitis. Of these 367 patients, 98 developed peritonitis, 44 of whom were treated with CR and 54 with C. MAIN OUTCOME MEASURES: Clinical response, divided into early (during the 2 weeks of therapy) and late (including the following 4 weeks) response. Success was defined as disappearance of all signs and symptoms by days 4-6, through day 42. Bacteriological response was either success (eradication) or failure (persistence, superinfection, or eradication with relapse/reinfection). RESULTS: The groups were comparable for age, sex, duration of continuous ambulatory/automated peritoneal dialysis, and occurrence of diabetes. Bacteriological cultures in both groups revealed predominantly gram positive micro-organisms. Initial and late clinical successes were obtained in 27/54 and 20/54 episodes (50% and 37%) in the C group, and 33/44 and 28/44 episodes (75% and 63.6%) in the CR group (p = 0.021 and p = 0.019). Bacteriological success occurred in 29.6% in the C group, and in 59.1% in the CR group (p= 0.026), with failure in 46.3% and 18.2%, respectively. Peritonitis episodes were bacteriologically not evaluable in 24.1% of episodes in the C group and 22.7% of episodes in the CR group, due mostly to no growth in the initial culture. CONCLUSION: The CIPPER Trial showed ciprofloxacin + rifampicin to be superior to cephradine as empiric treatment of peritonitis. PMID- 11757833 TI - Early glycated albumin, but not advanced glycated albumin, methylglyoxal, or 3 deoxyglucosone increases the expression of PAI-1 in human peritoneal mesothelial cells. AB - OBJECTIVE: The continuous contact of glucose-containing peritoneal dialysis (PD) fluids with the peritoneum results in the intraperitoneal formation of early and advanced glycation end-products. This nonenzymatic glycation of proteins may cause morphological and functional alterations to the peritoneum, which may contribute to patient dropout from PD therapy. Because fibrinolytic system components have been demonstrated to play an important role in the balance of intraperitoneal generation and degradation of fibrin, we studied the effect of early and advanced glycated human serum albumin, methylglyoxal, and 3 deoxyglucosone on the synthesis of tissue-type plasminogen activator (tPA), as well as its specific inhibitor (PAI-1), in human peritoneal mesothelial cells (HPMC). METHODS: Antigen concentrations in the supernatants of cultured HPMC were measured by ELISA. Northern blot analysis was conducted for mRNA expression. Electrophoretic mobility shift assays were applied to demonstrate the involvement of the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) in signal transduction. RESULTS: Incubation of HPMC with early glycated albumin (GHSA) resulted in a time- and concentration-dependent increase in PAI-1 mRNA expression and antigen secretion. In contrast, no changes in PAI-1 synthesis occurred after stimulation with either the 1,2-dicarbonyl compounds methylglyoxal and 3-deoxyglucosone, or with late advanced glycation end-products. tPA synthesis was not affected by any of the tested components. Furthermore, HPMC exposed to GHSA induced NF-kappaB and AP-1 DNA binding activity, suggesting that GHSA-induced overexpression of PAI-1 is transcriptionally regulated by both transcription factors. CONCLUSIONS: We conclude that Amadori modified glycated albumin upregulates PAI-1 synthesis in HPMC, possibly mediated through the activation of the transcription factors NF-kappaB and AP-1. The present data support the clinical relevance of the formation of glycated proteins and their involvement in pathological processes in PD patients. Thus, glycated albumin may contribute to an imbalance between intraperitoneal formation and degradation of fibrin that causes peritoneal structural alterations, with subsequent membrane failure. PMID- 11757834 TI - Expression of cancer antigen 125 by peritoneal mesothelial cells is not influenced by duration of peritoneal dialysis. AB - OBJECTIVE: To investigate the presence of cancer antigen 125 (CA125) on mesothelial cells in the effluent of peritoneal dialysis (PD) patients and to analyze the effect of duration of PD on the number of mesothelial cells in peritoneal effluent, the number of CA125-positive cells, and dialysate CA125 concentration. DESIGN: A cross-sectional study in which long-dwell peritoneal effluents were investigated for mesothelial cells and CA125. SETTING: A university hospital population of chronic PD patients. PATIENTS: 33 stable PD patients who were free of peritonitis during the investigation and during the 4 weeks prior to the study. METHODS: Examination of cytospin preparations of peritoneal effluent stained with May-Grunwald Giemsa, and also with an immunocytochemical double-staining method consisting of anticalretinin (pan mesothelial cell marker) and OC125. RESULTS: A close relationship was present between the numbers of mesothelial cells counted with the two staining methods (r= 0.998, p < 0.001). On average, 92% of mesothelial cells were positive for CA125, ranging between 75% and 100% in 80% of the patients. Correlations were found between the effluent CA125 concentration and the total number of mesothelial cells (r = 0.64, p < 0.001), and also the number of CA125-positive cells (r = 0.66, p < 0.001). A negative effect of time was seen on the effluent CA125 concentration, the total number of mesothelial cells, and the number of CA125-positive mesothelial cells. However, no effect of time was present on the percentage CA125-positive cells. CONCLUSIONS: On average, 92% of mesothelial cells in peritoneal effluent are positive for CA125. This figure is not dependent on the duration of PD. Long-term PD is associated with low dialysate CA125 concentrations, a low number of mesothelial cells, and a low number of CA125 positive mesothelial cells in effluent. These results support the hypothesis that dialysate CA125 can be used as a marker of mesothelial cell mass in stable PD patients. PMID- 11757835 TI - Expression of defensin antimicrobial peptides in the peritoneal cavity of patients on peritoneal dialysis. AB - OBJECTIVE: To investigate the expression and regulation of defensins in the peritoneal cavity of peritoneal dialysis (PD) patients. DESIGN: The presence of defensins in the peritoneal cavity was assessed using reverse transcription polymerase chain reaction (RT-PCR). In vivo defensin expression was analyzed in human peritoneal membrane biopsies and in peritoneal cavity leukocytes isolated from spent dialysate. Defensin expression in vitro was assessed in cultured human peritoneal mesothelial cells (HPMC) and confirmed with PCR Southern blot and DNA sequencing. The effect of tumor necrosis factor alpha (TNFalpha) and epidermal growth factor (EGF) on beta2 defensin expression in HPMC was analyzed by Northern blot analysis and RT-PCR respectively. RESULTS: Both alpha and beta classes of defensins are expressed in the peritoneal cavity of PD patients. Messenger RNA for the alpha-defensin human neutrophil peptide 3 and for beta-defensin-1 (hbetaD 1) were found in preparations containing predominantly peritoneal leukocytes, whereas beta-defensin-2 (hbetaD-2) is expressed by HPMC. HPMC isolated from different individuals displayed variability in both basal hbetaD-2 expression and in response to stimulation by TNFalpha. Conversely, EGF consistently downregulated the level of hbetaD-2 message in HPMC. CONCLUSION: Alpha- and beta defensins are expressed in the peritoneal cavity, and hbetaD-2 is the main defensin present in the peritoneal membrane. Variable levels of expression of hbetaD-2 by mesothelial cells were seen, with evidence of regulation by cytokines and growth factors. This provides evidence for a previously unknown mechanism of innate immunity at that site. PMID- 11757836 TI - The relationship between Kt/V(urea) and nPNA in anuric peritoneal dialysis patients: a comparison with predialysis patients. AB - OBJECTIVE: It is unknown whether a given level of urea clearance by the native kidneys provides better or similar control of uremia than the same level of urea clearance by continuous peritoneal dialysis (PD). More insight into possible differences between renal and peritoneal urea clearances is warranted. Therefore, we investigated the relationship between Kt/V(urea) and protein equivalent of total nitrogen appearance normalized to body weight (nPNA), the relationship between urea clearance and creatinine appearance, and other nutritional parameters in PD patients without residual renal function, and in predialysis end stage renal disease patients. PATIENTS: All patients participated in the Netherlands Cooperative Study on the Adequacy of Dialysis. This is a prospective cohort study of incident dialysis patients, in whom regular assessments of renal function are done. A group of 75 PD patients was identified at the first follow up assessment in which their urine production was less than 100 mL/day. These patients were considered the anuric group. This group was compared with a control group of 97 predialysis patients studied 0-4 weeks before the start of dialysis treatment. RESULTS: Linear relationships were present between Kt/V(urea) and nPNA, in both the predialysis patients and the anuric PD patients. A significant difference was present between the slopes of the two regression lines (0.40 vs 0.18, p = 0.007). When Kt/V(urea) exceeded 1.3/week, a given level of Kt/V(urea) was associated with a higher nPNA in predialysis than in anuric PD patients. Similar relationships were found between Kt(urea) and PNA. Kt(urea) was also significantly related to urine or dialysate creatinine appearance. A significant difference existed between the slopes of the regression lines in the two groups of patients (p < 0.001). A weekly Kt(urea) of 70 L was associated with a urine creatinine appearance of 11.0 mmol/day and a dialysate creatinine appearance of 8.4 mmol/day. Nutritional status measured with creatinine appearance and Subjective Global Assessment was better in the predialysis population, despite much lower values for Kt/V(urea) in these patients. CONCLUSIONS: The relationship between Kt/V(urea) and nPNA in anuric PD patients is different from that in a predialysis population. It follows from our results that, when Kt/V(urea) is above 1.3/week, a given level of Kt/V(urea) is associated with a higher nPNA in predialysis than in anuric PD patients. This challenges the concept of equivalency between renal and peritoneal Kt/V(urea) with respect to control of uremic morbidity. PMID- 11757837 TI - Icodextrin modeling error with PD ADEQUEST, version 2.0. PMID- 11757838 TI - Bicarbonate-lactate peritoneal dialysis in a patient with a mitochondriopathy. PMID- 11757839 TI - Peritoneal protein losses do not have a significant impact on nutritional status in CAPD patients. PMID- 11757841 TI - Is catheter function influenced by the side of the body in which the peritoneal dialysis catheter is placed? PMID- 11757842 TI - Local application of mupirocin at the peritoneal catheter exit site prevents early postoperative infections and should become standard practice. PMID- 11757840 TI - Serum insulin-like growth factor I levels do not correlate with residual renal function in dialysis patients. PMID- 11757843 TI - Re: Experience with a large dose (500 mg) of intravenous iron dextran and iron saccharate in peritoneal dialysis patients. PMID- 11757844 TI - Literature. September-October 2001. PMID- 11757845 TI - Overview of systemic fungal infections. AB - A steady increase in the frequency of invasive fungal infections has been observed in the past 2 decades, particularly in immunosuppressed patients. In recipients of bone marrow transplants, Candida albicans and Aspergillus fumigatus remain the primary pathogens. In many centers, however, Candida species other than C albicans now predominate, and many cases of aspergillosis are due to species other than A fumigatus. Additionally, heretofore unrecognized and/or uncommon fungal pathogens are beginning to emerge, including Blastoschizomyces capitatus, Fusarium species, Malassezia furfur, and Trichosporon beigelii. These opportunistic fungal pathogens are associated with various localized and disseminated clinical syndromes, and with substantial morbidity and mortality. These established, invasive mycoses, particularly in bone marrow transplant recipients, are the focus of this discussion. PMID- 11757846 TI - Antifungal prophylaxis in hematopoietic stem cell transplant recipients. AB - Efforts at preventing and treating fungal infection in hematopoietic stem cell transplant (HSCT) recipients must take into account the types of infections likely to be encountered during the different risk periods in hosts with different underlying risks. Given the emergence of molds as prevalent pathogens and the long duration of risk in allogeneic HSCT recipients, optimal antifungal prophylaxis would consist of treatment that can be given over a prolonged period and that would provide both anti-Candida and anti-Aspergillus activity. Optimal empiric therapy would consist of a broad-spectrum agent in the absence of more sensitive and specific methods for microbial diagnosis. Fluconazole (Diflucan) is currently the standard prophylactic agent for candidiasis, although mold-active agents and alternative strategies for polyene administration are being investigated. The gold standardfor empiric therapy is currently a polyene antifungal, yet an increased appreciation for amphotericin B-resistant yeasts and molds, and less toxic mold-active alternatives, might lead to the use of other compounds in the future. The recent development of multiple alternatives emphasizes our need to establish treatment algorithms that consider both the likely pathogens and potential toxicities. PMID- 11757847 TI - A brief review of antifungal therapy for deep fungal infection. AB - With the continuing increase in clinically important fungal disease, especially seen in the neutropenic patient, the need for new and improved systemic antifungal agents marches on. A pharmacy and therapeutics committee may select an antifungal agent based on these criteria: spectrum of action, pharmacokinetic profile, toxicity, potential for resistance, and cost. A number of agents are now available for treating deep fungal infections, including amphotericin B in conventional and liposomalformulations, and the triazoles itraconazole (Sporanox) and fluconazole (Diflucan). It is important to note that there is lack of agreement in practice over what constitutes ideal therapy. The lipidformulations of amphotericin B and the improved oral solution and new intravenous formulation of itraconazole are recent additions to therapeutic options that are already having a significant influence on drug selection and treatment practices. PMID- 11757849 TI - Role of ion track filters in environmental surveillance. AB - Ion track filters (ITFs) are produced by physiochemical treatments to thin films of polymers and mica irradiated by heavy ions. These ITFs have many applications in the fields of science and technology. In the present investigation, the developed ITFs from polycarbonate films have been used to filter bacteria of various types in water. It is observed that the electric conduction through these filters depends upon the concentration of contaminants and pore diameter of filters. Filtration experiments were carried out using both single and multipore filters. Other applications related to environment surveillance have also been reported. PMID- 11757848 TI - European experience with oral solution and intravenous itraconazole. AB - The availability of an improved oral solution and an intravenous (IV) formulation of itraconazole (Sporanox) promises to have an effect on prevention and treatment of fungal infection in immunocompromised patients. Use of itraconazole in neutropenic patients with hematologic malignancies has been evaluated in a number of European studies. Treatment with IV followed by oral itraconazole resulted in response or stable disease in two-thirds of patients with invasive pulmonary aspergillosis. Empiric treatment with IV followed by oral solution itraconazole was at least as effective as, and significantly less toxic than, amphotericin B. Several studies of oral solution prophylaxis indicate effectiveness in prevention of fungal infection. Oral solution and IV itraconazole are useful in a variety of situations in prophylaxis, empiric therapy, and treatment of probable/confirmed infection. Itraconazole exhibits a broad spectrum of activity against Aspergillus and Candida species. It has potential advantages over fluconazole (Diflucan), which does not exhibit in vitro activity against Aspergillus and most non albicans Candida species, and amphotericin B, which is associated with a high incidence of toxicity. Aggressive use of itraconazole and amphotericin B preparations in treatment of fungal infection at Royal Free Hospital may have reduced mortality associated with aspergillosis. PMID- 11757850 TI - Effects of environmental factors on the seasonally change of phytoplankton populations in a closed freshwater pond. AB - The effect of environmental factors affecting the population dynamic of phytoplankton population was studied seasonally in a closed freshwater pond with the natural water of Lake Kasumigaura, Japan. The predominant phytoplankton species in the pond were classified as Oscillatoria tenuis, Synedra ulna, Chlamydomonas cingulata and Cyclotella kutzingiana, with dominant species of Melosira italica, Synechococcus sp. and Cryptomonas ovata. The most important limiting factor for filament length and cell size of most of the phytoplankton community was temperature. Availability of most nutrients had profound effects on the phytoplankton growth as nonlimiting factors. Based on our results, it is suggested that cell cycle progression was also temporally regulated by a multiplicity of external factors such as temperature, nutrients, dissolved oxygen (DO) and pH. At high pH and high temperature, consistent increase of cell division of some phytoplanketers such as Synedra, Cyclotella, Chlamydomonas and Melosira occurs, and there also may be species-specific responses for other species of phytoplankters. In addition, the cell divisions of phytoplankters are differentially regulated in different phytoplankton species. PMID- 11757851 TI - Toxicity evaluation of sewage sludges in Hong Kong. AB - Anaerobically digested sewage sludges collected from four wastewater treatment plants located in Sha Tin, Tai Po, Yuen Long, and Shek Wu Hui in Hong Kong were subjected to chemical characterization and toxicity testing to provide preliminary assessment of their suitability for land application. All sewage sludges were slightly alkaline with pH range of 8.3-8.7. Electrical conductivity (EC; 0.69 dS m(-1)) and soluble NH4-N content (996 mg kg(-1)) of sewage sludge from Yuen Long were lower than that of other plants. Concentrations of heavy metals were determined as total, extractable, and water-soluble fraction using mixed acid digestion, DTPA (pH 7.3), and distilled water, respectively. Yuen Long sludge was most polluted with Zn and Cr higher than the pollutant concentration limits listed in Part 503 of USEPA, owing to the effluent coming from the tannery industry. High concentration of Ni was found in sludge from Sha Tin that originated mainly from the electroplating industry. DTPA-extractable Zn contents were high in sludges from Yuen Long (1247 mg kg(-1)) and Shek Wu Hui (892 mg kg( 1)), while 3.7 mg kg(-1) of DTPA-extractable Cr was found in Yuen Long sludge. Metal speciation of sludges showed that Pb was major in residual phase while Cu, Cr, and Ni in organic and residual phases, and Zn did not show any dominant chemical phase. The sludge extracts did not exert significant adverse effect on seed germination of Brassica chinensis (Chinese cabbage), but Yuen Long sludge caused a reduction in root growth. In view of its lower EC and soluble ammonia contents, the high concentration of Zn and Cr in Yuen Long sludge would likely be responsible for this adverse effect on root growth. Therefore, Yuen Long sludge would likely have a more serious impact on soil quality and plant growth as compared to other sludges. This would require further verification from greenhouse and field experiments. PMID- 11757852 TI - The toxins of Lyngbya majuscula and their human and ecological health effects. AB - Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles. PMID- 11757853 TI - Rare earth element content in various waste ashes and the potential risk to Japanese soils. AB - Selected chemical characteristics of rare earth elements (REEs) in 89 waste ash samples, including food scrap ashes (FSA), animal waste ashes (AWA), horticulture waste ashes (HWA), sewage sludge ashes (SSA) and incinerator bottom ashes (IBA), were examined in this study. The results showed that Y, La, Ce, Pr, Nd, Dy, Yb, Ho, Er, Tm, Lu in the waste ash samples were normally distributed, but Sc, Sm, Eu, Gd, Tb were not. Average REE concentrations followed the sequence of Ce > La = Y> Sc>Nd>Sm>Pr>Gd>Dy>Eu>Tb>Er> Yb>Ho>Lu>Tm. Of the five types of waste ashes, total REE contents (sigmaREE) ranged from 54 to 130 mg/kg, following the sequence of SSA>HWA>IBA>AWA>FSA; individual REE concentrations were within 0.04-20, 0.1 29, 0.2-33, 0.1-44 and 0.01-41 mg/kg for FSA, AWA, HWA, SSA and IBA, respectively. Crust-normalized REE patterns indicated that SSA was enriched with Sc, Sm, Eu, Gd, Tb and slightly enriched with La, Ce; IBA was enriched with Eu, Tb and slightly with La, Y, Ce; FSA was slightly enriched with Sm, Eu, Tb; REEs were not found to be elevated in HWA and AWA. Comparison of REE content in the waste ashes and in six principal Japanese agricultural soils indicated that application of FSA, AWA and HWA to agricultural land will cause no REE problem, but continuous application of SSA or IBA may cause Sc, Sm or Eu accumulation in some of the soils. PMID- 11757854 TI - A review of the contamination of soil with lead II. Spatial distribution and risk assessment of soil lead. AB - Contamination of soil with lead has occurred on a global scale. Exposure to lead may cause adverse effects to human health and the environment. It is therefore desirable to obtain a quantitative estimate of the potential risk of lead contamination. Numerous studies have been conducted collecting lead concentration data from both natural and contaminated soil on a range of scales. Very few of these studies have made serious attempts to spatially describe the data. In order to identify contaminated land and to enable development of appropriate environmental guidelines, it is essential to have an understanding of the universal range of lead concentrations. Such data also assists in assessing any potential risk to the environment or human health. This paper reviews the multitude of data collected on soil Pb concentrations. Lead surveys are discussed on the basis of land use, with Australian data presented separately. Data from lead surveys of agricultural, urban and industrial areas, as well as nationwide surveys are summarised. A small but increasing number of studies have employed spatial prediction techniques such as kriging to map the distribution of lead concentrations in soil. These studies are also summarised and a brief description of the basis for their use presented. Finally, environmental and health risk assessment is discussed and some methodologies in use around the world reviewed. PMID- 11757856 TI - Who are the humanitarians? PMID- 11757855 TI - Bioanalytical screening methods for dioxins and dioxin-like compounds a review of bioassay/biomarker technology. AB - Determination of environmental pollutants utilizing biodetectors such as bioassays, biomarkers, enzyme immunoassays (EIAs), or other bioanalytical tools is a continuously growing area. The present literature review describes the principles and advantages/limitations of several bioanalytical detection methods (BDMs) for the screening and diagnosis of dioxin and dioxin-like compounds. This study characterizes briefly the family of dioxin and dioxin-like compounds, discusses potential Ah receptor (AhR) ligands and cytochrome P-450 (CYP) 1A1 enzyme-inducing compounds. 'Milestones' in the development of BDMs are summarized and explained in detail for a number of bioanalytical tools that can be used to detect these classes of dioxin-like persistent bioaccumulative toxicants (PBTs). The design of a screening profile with a battery of bioassays/biomarkers coupled with the chemical analysis is evaluated. The relative potencies (REPs) to 2,3,7,8 TCDD for dioxin-like compounds are reviewed for various BDMs and the differences are noted. PMID- 11757857 TI - Athletic stress fractures: part I. History, epidemiology, physiology, risk factors, radiography, diagnosis, and treatment. AB - This 3-part article is a comprehensive review of the literature on athletically induced (fatigue) stress fractures. As typical signs and symptoms of stress fracture may differ slightly depending on the bone involved, physicians examining a fracture need to be aware of these subtle differences. Stress fractures are the result of excessive loading of bone. (Excessive loading is caused by muscle pull, fatigue loading, or both and may be exacerbated by anatomic risk factors, age, and sex. Loading leads to a metabolic response by osteoclasts and osteoblasts. This response, which normally helps bone heal, instead causes the stress fracture.) Stress fractures resolve with 6 to 8 weeks of rest and rehabilitation. Part 1 of this article focuses on the history, epidemiology, physiology, risk factors, radiography, diagnosis, and treatment of stress fractures. Part 2 reviews the specifics of stress fractures involving the lower body--the lower extremities, pelvic girdle, and feet and ankles. Part 3 reviews the specifics of stress fractures involving the upper body-shoulder girdle and thoracic region, upper extremities, hands and wrists, and pars interarticularis--and includes a special section on the female athlete. (Parts 2 and 3 will appear in the next issue.) PMID- 11757858 TI - Contribution of acetabular labrum to articulating surface area and femoral head coverage in adult hip joints: an anatomic study in cadavera. AB - The purpose of our study was to describe the gross anatomy of the adult acetabular labrum and to determine its contribution to the depth, surface area, and volume of the acetabulum. Fifty-five embalmed hips were studied. Each hip was disarticulated, and standardized measurements were taken. Calculations of the acetabular articulating surface area and volume, with and without the labrum, were performed based on these measurements. Average width of the acetabular labrum was 5.3 mm (SD, 2.6 mm). The labrum was wider anteriorly and superiorly than posteriorly. The surface area of the acetabulum without the labrum was 28.8 cm2; with the labrum, it was 36.8 cm2 (P < .0001). The volume of the acetabulum without the labrum was 31.5 cm3; with the labrum, it was 41.1 cm3 (P < .0001). There was no side-to-side difference in contribution of the labrum to either surface area or volume between right and left hips. Comparison of these indices for males and females showed statistically significant differences in absolute but not relative increases. PMID- 11757859 TI - Intraneural ganglion of the peroneal nerve: importance of timely diagnosis. AB - Peroneal nerve ganglion cysts typically present because of a palpable mass or symptoms and signs of entrapment neuropathy, including pain, diminished sensation, and motor weakness. Surgical treatment is usually successful when performed early, but, when diagnosis is delayed, intraneural growth and invasion may cause irreversible axonal injury and footdrop. This case report illustrates the importance of timely diagnosis when treating a ganglion of the peroneal nerve and reviews the appropriate workup, differential diagnosis, and treatment. PMID- 11757861 TI - Carpal bone osteonecrosis. PMID- 11757862 TI - Postpartum de Quervain's tenosynovitis of the wrist. PMID- 11757863 TI - Newly described adipocytic lesions. AB - This article reviews the clinicopathologic features and differential diagnoses of 7 newly described adipocytic lesions: chondroid lipoma, myolipoma, lipomatous hemangiopericytoma, sclerotic lipoma, fibrohistiocytic lipoma, hemosiderotic fibrohistiocytic lipomatous lesion, and spindle cell liposarcoma. Two recently described variants of spindle cell/pleomorphic lipoma are also presented: the pseudoangiomatous variant and the dendritic fibromyxolipoma, which corresponds in all likelihood to a peculiar myxoid variant of spindle cell lipoma. PMID- 11757864 TI - Cutaneous lipomatous neoplasms. AB - Benign and malignant lipomatous tumors are the most common neoplasms of subcutaneous and deep soft tissues in adults. In contrast, purely cutaneous lipogenic neoplasms are exceptionally rare, and some entities and variants of adipocytic neoplasms have not yet been described in the skin. In addition, some dermal lipogenic neoplasms are characterized by different specific clinicopathologic features in comparison with more deeply located tumors. Cutaneous angiolipoleiomyoma ("angiomyolipoma") is seen most often in male patients and in an acral location. It is characterized histologically by mature adipocytes, thick-walled blood vessels, and smooth muscle cells arranged in well defined fascicles and around blood vessels. Smooth muscle cells in cutaneous angiolipoleiomyoma stain negatively for HMB-45, in contrast to renal and extrarenal angiomyolipoma. Adenolipoma of the skin is a superficially located form of lipoma composed of large lobules of mature adipocytic tissue admixed with eccrine ducts and glands. Cutaneous spindle cell/pleomorphic lipomas, in contrast to subcutaneous forms, are more common in female patients and have a wide anatomic distribution. Histologically, cutaneous spindle cell/pleomorphic lipomas are characterized by an infiltrative growth pattern mimicking more aggressive lesions. Rarely, liposarcoma may occur as a purely cutaneous lesion with a favorable clinical prognosis despite high-grade morphologic features in many cases. PMID- 11757865 TI - Well-differentiated liposarcoma (atypical lipomatous tumors). AB - Well-differentiated (WD) liposarcoma accounts for about 40% to 45% of all liposarcomas therefore representing the larger subgroup of adipocytic malignancies. It tends to occur equally in the retroperitoneum or the limbs followed by the paratesticular area and the mediastinum, with a peak incidence between the fifth and the seventh decades. WD liposarcoma is further subdivided in the adipocytic (lipoma-like), sclerosing, inflammatory, and spindle cell subtypes, of which the first two are by far the commoner. WD adipocytic liposarcoma is composed of a relatively mature adipocytic proliferation, featuring cell size variation as well as at least focal nuclear atypia. A varying number (from many to none) of lipoblasts may be found. Sclerosing WD liposarcoma is characterized microscopically by the presence of scattered distinctive bizarre stromal cells and multivacuolated lipoblasts set in a fibrillary collagenous background. Inflammatory liposarcoma represents a rare variant of WD liposarcoma in which a chronic inflammatory infiltrate predominates to the extent that the differential diagnosis is mainly with nonadipocytic lesions such as inflammatory myofibroblastic tumor, Castleman's disease, and Hodgkin's as well as non Hodgkin's lymphomas. Spindle cell liposarcoma is the rarest variant and is composed neural-like spindle cell proliferation set in a fibrous and/or myxoid background and associated with an atypical lipomatous component which usually includes lipoblasts. Cytogenetically, WD liposarcoma appears to be relatively homogenous exhibiting characteristic ring as well as giant marker chromosomes containing amplified genetic material derived from the 12q13-15 chromosome region. As WD liposarcomas of any type have no potential for metastasis unless they undergo dedifferentiation, the opportunity to replace the term "WD liposarcoma" with a less frightening denomination has produced a long, sharp debate. WD liposarcoma and atypical lipoma should be considered as synonyms and their use should therefore be determined by the degree of reciprocal comprehension between the surgeon and the pathologist to prevent either inadequate or excessive treatment. PMID- 11757866 TI - Dedifferentiated liposarcoma. AB - Dedifferentiated liposarcoma is a high-grade nonlipogenic sarcoma that arises in a background of a preexisting well-differentiated liposarcoma. The phenomenon of dedifferentiation is time dependent, and primary or de novo tumors exceed secondary neoplasms in a ratio of 9:1. The tumor occurs most frequently in adults beyond the 6th decade of life, slightly predominates in men, and involves the abdominal cavity most often. Pleomorphic malignant fibrous histiocytoma-like histologic features are the most commonly observed phenotype, although other sarcomatous phenotypes have been described less frequently. Surgical treatment is the main form of therapy for dedifferentiated liposarcoma, which is associated with a reported local recurrence rate of 41% to 52%, 15% distant metastatic rate, and 30% disease-related mortality rate. On a chromosomal level, dedifferentiated liposarcoma frequently displays the same chromosomal abnormality associated with well-differentiated liposarcomas--ie, the presence of a supernumerary ring or giant chromosome derived from the 12q(13-15) region. PMID- 11757867 TI - Myxoid and round cell liposarcoma: a spectrum of myxoid adipocytic neoplasia. AB - Myxoid and round cell liposarcoma accounts for about 30% to 35% of all liposarcomas and, even if still classified by the World Health Organization (WHO) as 2 distinct subtypes, share both clinical and morphologic features. Lesions combining both patterns are frequent and wide agreement exists in considering round cell liposarcoma as the high grade counterpart of myxoid liposarcoma. Furthermore, myxoid and round cell liposarcoma share the same characteristic chromosome change represented most frequently by a reciprocal translocation t(12;16)(q13;p11) that fuses the CHOP gene with the TLS gene. Clinically, myxoid and round cell liposarcoma tend to occur in the limbs with a peak incidence ranging between the third and the fifth decade and exhibit overall a metastatic rate of approximately 30%. A peculiar tendency to metastasize to the soft tissue is observed that should not be interpreted as multicentricity. Microscopically, purely myxoid liposarcoma is composed by a hypocellular spindle cell proliferation set in a myxoid background and associated with a varying number of monovacuolated lipoblasts. The most helpful morphologic clue is represented by the presence of a thin-walled capillary network organized in a plexiform pattern. The most important morphologic variation observed in myxoid liposarcoma is represented by the occurrence of hypercellular areas that may exhibits an undifferentiated round cell morphology. On the basis of the percentage of hypercellularity/round cell formation, a myxoid/round cell liposarcoma (more than 25% hypercellular/round cell areas) and a round cell liposarcoma (more than 75% hypercellular/round cell areas) are somewhat arbitrarily recognized. Both the recognition and the quantification of hypercellular/round cell areas represents a crucial step in the evaluation of this liposarcoma subtype because hypercellularity appears to correlate with the clinical outcome. In consideration of the intrinsic difficulty in establishing accurately the percentage of high grade areas as well as of application of different cut off values, it appears safer to consider any amount of hypercellularity as prognostically relevant. Careful as well as extensive sampling is mandatory to permit detection of the smallest amount of hypercellularity. The differential diagnosis of myxoid liposarcoma includes benign lesions, such as myxoid spindle cell lipoma, intramuscular myxoma and lipoblastoma, and malignant ones such as low grade myxofibrosarcoma, and extraskeletal myxoid chondrosarcoma. In consideration of the great morphologic variability, the application of both immunohistochemistry and genetics has proved helpful in sorting out the more challenging cases. PMID- 11757868 TI - Pleomorphic liposarcoma. AB - Pleomorphic liposarcoma (PLS) is defined as a high-grade pleomorphic sarcoma containing multivacuolated lipoblasts. PLS arises most frequently in the extremities of older individuals and often metastasizes to the lungs. The prognosis of PLS parallels that of many other high-grade sarcomas. In a small analysis combining clinicopathologic data available from 16 previously reported and 8 additional cases of PLS arising in the extremities, the 5-year overall survival rate for the 24 patients was 40% (median survival, 48 months). By univariate analysis, patients with tumors located in the upper extremities (P = .021) and greater than 10 cm (P = .047) had decreased overall survival. Older age, female sex, epithelioid phenotype, and radiotherapy or chemotherapy administration were not significantly associated with an adverse outcome. PMID- 11757869 TI - The genetics of lipomatous tumors. AB - The current classification of lipomatous neoplasms has been validated by the identification of characteristic cytogenetic and molecular genetic profiles associated with various neoplasms within the family of lipomatous tumors. The review describes characteristic cytogenetic and molecular genetic profiles and discusses their significance. The clinicopathologic features of these tumors, which are described elsewhere, will not be included in this review. PMID- 11757870 TI - Integration of the ecological and error models of overconfidence using a multiple trace memory model. AB - A memory processes account of the calibration of probability judgments was examined. A multiple-trace memory model, Minerva-Decision Making (MDM; M. R. P. Dougherty, C. F. Gettys, & E. E. Ogden, 1999), used to integrate the ecological (Brunswikian) and the error (Thurstonian) models of overconfidence, is described. The model predicts that overconfidence should decrease both as a function of experience and as a function of encoding quality. Both increased experience and improved encoding quality result in lower variance in the output of the model, which in turn leads to improved calibration. Three experiments confirmed these predictions. Implications of MDM's account of overconfidence are discussed. PMID- 11757871 TI - Why children learn color and size words so differently: evidence from adults' learning of artificial terms. AB - An adult simulation study examined why children's learning of color and size terms follow different developmental patterns, one in which word comprehension precedes success in nonlinguistic matching tasks versus one in which matching precedes word comprehension. In 4 experiments, adults learned artificial labels for values on novel dimensions. Training mimicked that characteristic for children learning either color words or size words. The results suggest that the learning trajectories arise from the different frames in which different dimensions are trained: Using a comparison (size-like) training regimen helps learners pick out the relevant dimension, and using a categorization (color-like) training regimen helps the learner correctly comprehend and produce dimension terms. The results indicate that the training regimen, not the meanings of the terms or the specific dimensions, determines the pattern of learning. PMID- 11757872 TI - How are visuospatial working memory, executive functioning, and spatial abilities related? A latent-variable analysis. AB - This study examined the relationships among visuospatial working memory (WM) executive functioning, and spatial abilities. One hundred sixty-seven participants performed visuospatial short-term memory (STM) and WM span tasks, executive functioning tasks, and a set of paper-and-pencil tests of spatial abilities that load on 3 correlated but distinguishable factors (Spatial Visualization, Spatial Relations, and Perceptual Speed). Confirmatory factor analysis results indicated that, in the visuospatial domain, processing-and storage WM tasks and storage-oriented STM tasks equally implicate executive functioning and are not clearly distinguishable. These results provide a contrast with existing evidence from the verbal domain and support the proposal that the visuospatial sketchpad may be closely tied to the central executive. Further, structural equation modeling results supported the prediction that, whereas they all implicate some degree of visuospatial storage, the 3 spatial ability factors differ in the degree of executive involvement (highest for Spatial Visualization and lowest for Perceptual Speed). Such results highlight the usefulness of a WM perspective in characterizing the nature of cognitive abilities and, more generally, human intelligence. PMID- 11757873 TI - Working memory and the control of action: evidence from task switching. AB - A series of 7 experiments used dual-task methodology to investigate the role of working memory in the operation of a simple action-control plan or program involving regular switching between addition and subtraction. Lists requiring switching were slower than blocked lists and showed 2 concurrent task effects. Demanding executive tasks impaired performance on both blocked and switched lists, whereas articulatory suppression impaired principally the switched condition. Implications for models of task switching and working memory and for the Vygotskian concept of verbal control of action are discussed. PMID- 11757874 TI - Statistical learning in a serial reaction time task: access to separable statistical cues by individual learners. AB - The ability of adult learners to exploit the joint and conditional probabilities in a serial reaction time task containing both deterministic and probabilistic information was investigated. Learners used the statistical information embedded in a continuous input stream to improve their performance for certain transitions by simultaneously exploiting differences in the predictability of 2 or more underlying statistics. Analysis of individual learners revealed that although most acquired the underlying statistical structure veridically, others used an alternate strategy that was partially predictive of the sequences. The findings show that learners possess a robust learning device well suited to exploiting the relative predictability of more than I source of statistical information at the same time. This work expands on previous studies of statistical learning, as well as studies of artificial grammar learning and implicit sequence learning. PMID- 11757875 TI - Do threatening stimuli draw or hold visual attention in subclinical anxiety? AB - Biases in information processing undoubtedly play an important role in the maintenance of emotion and emotional disorders. In an attentional cueing paradigm, threat words and angry faces had no advantage over positive or neutral words (or faces) in attracting attention to their own location, even for people who were highly state-anxious. In contrast, the presence of threatening cues (words and faces) had a strong impact on the disengagement of attention. When a threat cue was presented and a target subsequently presented in another location, high state-anxious individuals took longer to detect the target relative to when either a positive or a neutral cue was presented. It is concluded that threat related stimuli affect attentional dwell time and the disengage component of attention, leaving the question of whether threat stimuli affect the shift component of attention open to debate. PMID- 11757876 TI - On the fragility of skilled performance: what governs choking under pressure? AB - Experiments 1-2 examined generic knowledge and episodic memories of putting in novice and expert golfers. Impoverished episodic recollection of specific putts among experts indicated that skilled putting is encoded in a procedural form that supports performance without the need for step-by-step attentional control. According to explicit monitoring theories of choking, such proceduralization makes putting vulnerable to decrements under pressure. Experiments 3-4 examined choking and the ability of training conditions to ameliorate it in putting and a nonproceduralized alphabet arithmetic skill analogous to mental arithmetic. Choking occurred in putting but not alphabet arithmetic. In putting, choking was unchanged by dual-task training but eliminated by self-consciousness training. These findings support explicit monitoring theories of choking and the popular but infrequently tested belief that attending to proceduralized skills hurts performance. PMID- 11757877 TI - The dawning of a past: the emergence of long-term explicit memory in infancy. AB - The ability to recall information about the past is thought to emerge in the 2nd half of the 1st year of life. Although there is evidence from both cognitive neuroscience and behavioral psychology to support this hypothesis, there is little longitudinal evidence with which the question can be addressed. Infants' memory abilities were tested between the ages of 9 and 16 months using elicited and deferred imitation. Infants' memory for events was tested after delays ranging from 1 to 6 months. The results suggest that at 9 months of age, infants are able to store and retrieve representations over delays of as many as 4 weeks but not over long delays. In contrast, 10-month-olds have at their disposal a system that allows encoding and retrieval of event representations over delays of up to 6 months. These results support the idea that the system that underlies long-term ordered recall emerges near the end of the 1st year of life. PMID- 11757878 TI - Context processing in older adults: evidence for a theory relating cognitive control to neurobiology in healthy aging. AB - A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions. PMID- 11757879 TI - Task preparation and task repetition: two-component model of task switching. AB - The switch cost (the disadvantage of performing a new task vs. a repeated task) has been attributed to lack of preparation for the switched task or priming of the repeated task. These sources were examined by manipulating foreknowledge of task transition (repeat or switch), response-to-stimulus interval (RSI), and practice level. Regardless of foreknowledge, the cost decreased with RSI and practice. The reduction was greater with foreknowledge than with no foreknowledge, and the amount of switch cost did not depend on foreknowledge. These results suggest that the switch cost with foreknowledge may consist of both inadequate preparation and repetition benefit but the switch cost with no foreknowledge may reflect repetition benefit only. An ACT-R (adaptive control of thought-rational) model was proposed, accommodating both preparation and priming effect with 2 independent processes: conflict resolution among productions and decay of chunk activation. PMID- 11757880 TI - An analysis of ideomotor action. AB - This article presents a framework based on the work of R. H. Lotze (1852), W. James (1890), and A. G. Greenwald (1970) for understanding ideomotor actions that tend to arise when individuals watch others perform certain actions. Two principles of ideomotor action induction are distinguished: perceptual induction, in which people tend to perform the movements they see, and intentional induction, in which people tend to perform movements suited to achieve what they would like to see. In 3 experiments, ideomotor hand, head, and foot movements were studied while participants watched a ball traveling toward a target. Results showed strong support for intentional induction, weaker support for perceptual induction, and a strong impact of the effector studied. The representational basis of action induction (stimulus vs. goal representations) and the automaticity of the underlying processing (task-dependent vs. task-independent induction) were considered. PMID- 11757881 TI - Multisensory prior entry. AB - Despite 2 centuries of research, the question of whether attending to a sensory modality speeds the perception of stimuli in that modality has yet to be resolved. The authors highlight weaknesses inherent in this previous research and report the results of 4 experiments in which a novel methodology was used to investigate the effects on temporal order judgments (TOJs) of attending to a particular sensory modality or spatial location. Participants were presented with pairs of visual and tactile stimuli from the left and/or right at varying stimulus onset asynchronies and were required to make unspeeded TOJs regarding which stimulus appeared first. The results provide the strongest evidence to date for the existence of multisensory prior entry and support previous claims for attentional biases toward the visual modality and toward the right side of space. These findings have important implications for studies in many areas of human and animal cognition. PMID- 11757882 TI - A cross-national study of acute otitis media: risk factors, severity, and treatment at initial visit. Report from the International Primary Care Network (IPCN) and the Ambulatory Sentinel Practice Network (ASPN). AB - BACKGROUND: Treatment of acute otitis media (AOM) differs worldwide. The Dutch avoid antimicrobials unless fever and pain persist; the British use them for 5 to 7 days, and Americans use them for 10 days. If effects of therapies are to be compared, it is necessary to evaluate rates of risk factors, severity of attacks, and their influence on treatment decisions. We wanted to compare the prevalence of risk factors for AOM and evaluate their association with severity of attacks and of severity with antimicrobial treatment. METHODS: We undertook a prospective cohort study of 2,165 patients with AOM enrolled by primary care physicians; 895 were enrolled from North America, 571 were enrolled from the United Kingdom, and 699 were enrolled from The Netherlands. The literature was searched using the key words "acute otitis media," "severity," and "international comparisons." RESULTS: The prevalence of several AOM risk factors differs significantly among patients from the three country networks; these factors include race, parent smoking habits, previous episodes, previous episodes without a physician visit, tonsillectomy or adenoidectomy, frequency of upper respiratory tract infections, day care, and recumbent bottle-feeding. Dutch children have the most severe attacks as defined by fever, ear discharge, decreased hearing during the previous week, and moderate or severe ear pain. In country-adjusted univariate analyses, increasing age, exposure to tobacco smoke, day care, previous attacks of AOM, previous attacks without physician care, past prophylactic antimicrobials, ear tubes, adenoidectomy, and tonsillectomy all contribute to severity. Only country network, age, history of AOM, previous episode without physician care, and history of adenoidectomy and tympanostomy tubes are independently related to increased severity, while current breast-feeding is protective. Severity of attacks influences treatment decisions. Dutch children are least likely to receive antimicrobials, and even for severe attacks the British and Dutch physicians usually use amoxicillin or trimethoprim-sulfa; North American children with severe attacks are more likely to receive a broad-spectrum second-line antimicrobial. CONCLUSION: Dutch children have the highest ratings in all severity measures, possibly reflecting parental decisions about care seeking for earaches. When comparing groups of patients with AOM, it is necessary to adjust for baseline characteristics. Severity of episode affects physician treatment decisions. Adoption of Dutch guidelines restricting use of antimicrobials for AOM in the United States could result in annual savings of about $185 million. PMID- 11757883 TI - Clinical obstetric outcomes related to continuity in prenatal care. AB - BACKGROUND: Continuity of care has long been considered a benefit to patients of family physicians, but quantifying these benefits has been problematic. Previous studies focused on patient preferences and relationship issues, whereas evidence regarding clinical endpoints has been lacking. This study reports differences in obstetric and neonatal outcomes related to continuity in prenatal care. METHODS: Using an historical prospective design, data were collected on 494 maternal-fetal dyads in two groups. One (named GAP, n = 40) received a high degree of continuity in their prenatal care, and one (named NHC, n = 454) received relatively little. Analyses were performed to determine not only the outcome differences between the groups, but also to what factor(s) these differences were attributable. RESULTS: The continuity in prenatal care group had better outcomes in neonatal morbidity, birth weight, maternal weight gain, and both Apgar scores. None of these differences was directly attributable to continuity. Rather, continuity in prenatal care was associated with the observed increase in the number of prenatal visits, which in turn was shown to be a significant factor in the greater birth weights and maternal weight gain. None of the factors examined appears to explain the difference in neonatal morbidity. CONCLUSIONS: Women who receive prenatal care from a single physician are likely to receive more prenatal care, which is correlated with greater maternal weight gains and greater fetal birth weights. PMID- 11757884 TI - Technical competency in flexible sigmoidoscopy. AB - BACKGROUND: Family practice residencies offer training in flexible sigmoidoscopy; however, there are no objective recommendations for determining competency in learners. We describe a longitudinal study designed to determine the mean procedure time and depth of insertion for family practice residents. METHODS: During a 21-month period, data were collected for 421 patients undergoing flexible sigmoidoscopy. Second- or third-year family medicine residents supervised by family medicine faculty did all procedures. The data were analyzed with simple descriptive statistics, t test, and linear and logistic regression. RESULTS: The mean procedure time was 18+/-9.3 minutes (17.2 - 19.6, 95% confidence interval [CI]). The mean insertion depth was 51.4+/-12.4 cm (50.4 - 52.6 cm, 95% CI). Performing a biopsy was associated with an increase in procedure time (17.0 vs 27.3 minutes, P < .0001). Women with a history of pelvic surgery had less depth of insertion than did those who had no history of pelvic surgery (47 vs 53 cm, P = .002, t test). CONCLUSION: Procedural competency consists of knowledge, technical skills, and attitudes. Knowledge and attitudes can be assessed with other items, such as examinations and observation. Primary care faculty can now use these standards of insertion depth and procedure time when determining technical skill proficiency for their residents in flexible sigmoidoscopy. PMID- 11757885 TI - Alcohol, tobacco, and drug use and the onset of type 2 diabetes among inner-city minority patients. AB - BACKGROUND: We examined the prevalence of alcohol, tobacco, and drug use and their relation to the age of onset of type 2 diabetes among inner-city minority diabetic patients who sought routine care at medical clinics in south central Los Angeles. METHODS: A cross-sectional study design was used to sample 392 diabetic patients. Consecutive patients from seven different primary care clinics were interviewed to determine their alcohol, tobacco, and drug use histories and the age of onset of diabetes. RESULTS: The study sample was 61% Hispanic and 64% female and had a mean age of 53 years. Seventy-one diabetic patients (18%) reported that they recently consumed alcohol. Sixty-nine patients (17%) reported smoking within 30 days of their interview. Thirty-eight diabetic patients reported a history of regular illicit drug use. Multiple regression analysis showed that diabetic patients who used alcohol, illicit drugs, or combined substances (alcohol and illicit drugs), but not tobacco alone, reported an earlier onset of type 2 diabetes. CONCLUSIONS: This hypothesis-generating study suggests that alcohol and illicit drugs, when used alone or in combination, might be associated with an earlier onset of type 2 diabetes. Additional research, however, is required to evaluate further these preliminary findings. PMID- 11757886 TI - Family physicians' use of medical abstracts to guide decision making: style or substance? AB - BACKGROUND: Many physicians rely on the abstracts of research articles to guide their clinical decision making. This need for expediency is one basis for many journals to reformat their abstracts. METHODS: To determine whether the format of medical abstracts affects physician decision making, we surveyed family physicians in Michigan, Pennsylvania, and Virginia. All participants were members of the American Academy of Family Physicians. The survey included three case scenarios (corneal abrasion, fibromyalgia, and hyperlipidemia) followed by structured and open-ended assessments of usual management. After assessing their usual management in each scenario, the respondents were provided with an abstract of a valid research paper. The format of abstracts (unstructured, IMRAD [introduction, methods, results, and discussion], structured, and POEM [patient oriented evidence that matters]) were randomly assigned. After reading the abstract, we assessed changes in management of the case scenario. RESULTS: Two hundred eighty-nine family physicians responded to the survey. At baseline, 187 (65%) of physicians patched corneal abrasions. After reading the abstract, 142 (76%) would no longer use eye patches. Two hundred forty-five (83%) of physicians did not use the combination of fluoxetine and amitriptyline for managing fibromyalgia. After reading the abstract, 179 (73%) would use combination therapy. Two hundred thirty-four (84%) of physicians used "statins" when managing hyperlipidemia. After reading the abstract, 211 (90%) would continue using statins. The format of abstract had no significant effect on physicians' decision making. CONCLUSIONS: Whereas the format of abstract in this study had no effect on physician decision making, having valid information available in the context of a clinical scenario appeared to influence decisions. PMID- 11757887 TI - Management of peripheral arterial disease and intermittent claudication. AB - BACKGROUND: Peripheral arterial disease (PAD) is the chronic obstruction of the arteries supplying the lower extremities. The most common symptom is intermittent claudication resulting in aching pain, numbness, weakness, or fatigue in the muscle groups of the lower extremities. METHODS: Using the key words "peripheral arterial disease," "intermittent claudication," "atherosclerosis," and "cardiovascular disease," MEDLINE databases were searched from 1970 to the present. The most recent articles pertinent to current treatment recommendations for PAD and intermittent claudication were selected to document this review. RESULTS AND CONCLUSIONS: Symptoms of intermittent claudication are induced by walking or exercise and usually resolve with rest. Disease severity varies from patients who are asymptomatic to those who have unremitting symptoms. A high overlap exists between PAD and coronary artery and cerebrovascular disease. Risks for long-term morbidity and mortality are identical for PAD, intermittent claudication, and coronary artery disease. Treatment of PAD is aimed at maintaining or improving functional status, reducing or eliminating ischemic symptoms, and preventing disease progression. Exercise and aggressive risk factor modification represent the cornerstones of treatment. Risk factors include smoking, diabetes, lipid abnormalities, hypertension, C-reactive protein, lipoprotein(a), and hyperhomocystinemia. Antiplatelet and lipid-altering therapies decrease risk of atherosclerotic vascular complications and are being studied to improve intermittent claudication. Cilostazol, a new antiplatelet, antithrombotic agent, reduces claudication symptoms. Angiogenic growth factors have shown preliminary success in patients with rest pain and ischemic ulcers and are being investigated for use in patients with intermittent claudication. Invasive revascularization procedures can be considered for patients with critical limb ischemia or when medical therapy fails. PMID- 11757888 TI - The diagnostic challenge of infective endocarditis: cutaneous vasculitis leading to the diagnosis of infective endocarditis. AB - BACKGROUND: Signs and symptoms of infectious endocarditis are protean. They result from destruction of cardiac endothelium, metastatic embolization, hematogenous seeding, and immune complex deposition. Embolic manifestations of infectious endocarditis can mimic several other pathologic conditions and make the diagnosis of infectious endocarditis difficult. METHODS: We describe a case of cutaneous vasculitis leading to the diagnosis of infectious endocarditis. A review of the literature highlights the variable clinical presentations and key diagnostic strategies in the evaluation of infectious endocarditis. RESULTS AND CONCLUSION: Infective endocarditis has protean clinical symptoms and signs and can be a challenging diagnosis. Being alert to the condition is crucial, and where a high clinical probability exists despite a negative transthoracic echocardiogram, diagnostic evaluation with transesophageal echocardiograph is required. PMID- 11757889 TI - Mycobacterium chelonae: nonhealing leg ulcers treated successfully with an oral antibiotic. AB - BACKGROUND: Mycobacterium chelonae is an important human pathogen and should be considered when a physician is faced with nonhealing cutaneous wounds, including ulcers of the lower leg. METHODS: The medical literature was searched from 1965 to the present using the key words "Mycobacterium chelonae" and "leg ulcers." A case of Mycobacterium chelonae infection is reported. RESULTS AND CONCLUSION: Clarithromycin as single-agent oral therapy has been effective in treating these infections once the proper diagnosis is established. Diagnosis of M. chelonae infection requires being alert to this infectious agent and obtaining cultures for mycobacteria. Aggressive surgical debridement with direct excision of the wound might now be unnecessary because of the effectiveness of oral clarithromycin administered as a single oral agent. PMID- 11757890 TI - Venous malformation of the palm in a collegiate crew athlete. PMID- 11757891 TI - Pyoderma gangrenosum in a patient with psoriatic arthritis. PMID- 11757892 TI - Initial presentation of systemic lupus erythematosus masquerading as bacterial meningitis. PMID- 11757893 TI - To treat or not to treat otitis media--that's just one of the questions. PMID- 11757894 TI - 61st annual meetings of the American Conference of Governmental Industrial Hygienists and the American Industrial Hygiene Association. PMID- 11757895 TI - Surveillance of safety and health programs and needs in small U.S. businesses. PMID- 11757896 TI - Control of wood dust from large diameter disc sanders. PMID- 11757897 TI - Methylene chloride exposures in two gluing operations. PMID- 11757898 TI - The influence of seam height on lost-time injury and fatality rates at small underground bituminous coal mines. AB - Due to variations in the thickness of U.S. coal seams, there is great variability in the height of the roof where underground miners work. Restrictions imposed by low seam heights have important safety consequences. As the height of their workplace decreases, miners must stoop, duck walk, or crawl, and their vision, posture, and mobility become increasingly restricted. Low seam height also places important restrictions on the design of mobile equipment and other mining machinery. Using the employment and injury data reported to the Mine Safety and Health Administration (MSHA) from 1990 to 1996, small underground bituminous coal mines with less than 50 employees were stratified by average coal seam height according to the following categories: low (< or =42"), medium (43"-60"), and high (> or =61"). Injury rates for both nonfatal days lost and fatality cases were examined by seam height and leading type of injury incidents. The leading types of incidents associated with fatalities were roof falls and powered haulage equipment. In comparison to high-seam mines, miners working in low or medium seams are at higher risk of being killed by powered haulage equipment, roof bolting machines, and falls of unsupported roof. The leading types of incidents associated with nonfatal injuries were handling materials and powered haulage. As mining height decreases, miners are at increasingly higher risk of having a nonfatal injury from incidents involving roof bolting machines, load-haul-dump equipment, personnel carriers, and powered haulage conveyors. As mining height increases, miners are at increasingly higher risk of having a nonfatal injury from slips and falls and incidents involving shuttle cars and roof and rib falls. Knee injuries are a particularly severe problem in low-seam mines. The rate of injuries to miners while crawling or kneeling is 10 times higher in low seams than in high seams. PMID- 11757899 TI - Worker exposure and health risks from volatile organic compounds utilized in the paint manufacturing industry of Kenya. AB - This study provides a means for the evaluation of cleaner manufacturing and the provision of cost-effective worker health improvements in developing nations. Individual worker exposure to volatile organic compounds was measured in the paint manufacturing plants of Nairobi, Kenya. A variety of different paint production jobs were monitored, including laboratory researchers, mixers, tinters, fillers, cleaners, raw materials deliverers, and resins producers. Exposure levels were calculated based on a time-weighted average over an entire 8 10 hour workday. The paint solvents used can cause both acute and chronic health problems for the workers exposed. For example, over half of the organics monitored, i.e. benzene, styrene, and xylene, exhibit carcinogenic properties. The lifetime cancer risk from exposure to these paint solvents was estimated utilizing published cancer potencies, and the risks range from 1.90 x 10(-4) for raw materials deliverers to 2.60 x 10-2 for cleaners. The highest exposure tasks included cleaning the mixing vats and mixing the paint product, ranging from risks of 8.5 x 10(-4) to 2.6 x 10(-2), providing evidence that solvent exposure occurs due to point sources. Because of this, simple and inexpensive technologies should significantly reduce the excess exposure of workers in these manufacturing facilities. The cost of minor-innovations in the plants themselves, such as fans, drum and mixing vat covers, and respirators, could amount to as much as five times less than the estimated cost of treating workers who develop cancer due to paint solvent exposure. PMID- 11757900 TI - A practical method for ergonomic and usability evaluation of hand tools: a comparison of three random orbital sander configurations. AB - Tool and equipment purchasing decisions are constantly made by companies and workers, often with little objective information beyond word of mouth and marketing information. This study presents a pilot investigation of random orbital sanders using ergonomic and usability assessment techniques which can easily be applied in any industry. Three subjects performed a sanding task using three different tool configurations: 1) the current model sander, 2) current model with hose-swivel attachment, and 3) the new "ergonomically designed" model. Physical measurements were taken of muscle activity and wrist motion to complement think-aloud testing and a usability questionnaire. No significant differences were found in physical measurements between the three configurations. Participants strongly preferred the current model over the new model, reporting less perceived discomfort and vibration, despite what appeared to be improvements in the new design. Workplace changes intended to reduce the risk of injury sometimes may have no effect after significant capital investment, or in some cases even increase the risk of injury. Practical assessment of new tools or modifications can quickly determine whether the outcome is indeed an improvement. The results of this tool assessment highlight the need for objective information in tool and equipment design decisions. PMID- 11757901 TI - The influence of trainee characteristics on the effectiveness of health and safety training for hazardous waste site operations work. AB - A 10-year retrospective analysis was done using training records for 869 trainees who had attended a 40-hour course for hazardous waste site work. The course is intended for professional site workers, but had been attended by a demographically diverse audience. Analysis of test, demographic, and course data revealed some spurious effects but also indicated that trainees were not disadvantaged in their learning gains based on their own background or that of the class overall. Moreover, a large class appears to present some advantages, and a diverse class appears to present advantages in training material applied across work duties (hands-on skills, decontamination, etc.). Logistics encountered in the study raise doubts that a definition of professional/nonprofessional can be achieved or applied. Overall, the routine practice of providing separate training to professionals and nonprofessionals requires revisiting. PMID- 11757902 TI - Musculoskeletal injuries in construction: a review of the literature. AB - The first step in addressing any problem is recognition of the problem and a measure of its size and scope. There have been few reviews to date of the evidence of a musculoskeletal disorders problem in construction, particularly in the United States. Construction contractors in the United States have questioned the existence of a musculoskeletal disorders problem in construction, so a review of the evidence is warranted. The types of evidence reviewed include: 1) historical evidence, 2) injury data, 3) workers' compensation data, 4) medical exam data, 5) survey data, and 6) exposure data. Injury data generally represent injuries that the employers have identified as work-related and recorded or reported. Workers' compensation data are from cases that have been filed by workers for compensation and quite often represent only "closed" cases where compensation has been awarded. Medical exam data are from physical examinations of workers. Symptom survey data are the most inclusive and show the number of workers who self-report musculoskeletal problems. Exposure data include measurements made of exposure to musculoskeletal risk factors. The existing data show construction workers to be at significant risk of musculoskeletal injury, specifically related to the work they do. Their risk of musculoskeletal injury is much higher than that of other workers who have less heavy work, about 50 percent higher than all other workers. Several trades have been extensively studied, while others have been studied to a lesser extent. While the exact relationship between exposures and injuries is complex and often multifaceted, it would be difficult to deny the existence of the problem and the fact that these injuries are, to a great extent, related to the work that construction workers perform. PMID- 11757903 TI - Indoor environmental quality in six commercial office buildings in the midwest United States. AB - The aims of this study were to characterize physical, mechanical, and environmental factors influencing indoor environmental quality (IEQ) in commercial office buildings; document occupant perceptions and psychosocial attributes; and evaluate relationships among these parameters. Six large office buildings in metropolitan areas were selected in Iowa, Minnesota, and Nebraska. Comprehensive sampling was conducted over one week in each building, during all four seasons. This paper presents the study methods and selected results from the first round of sampling (November 1996 to April 1997). Air flow and recirculation rates were quite variable, with the proportion of outdoor air provided to occupants ranging from 10 to 79 CFM/person. Carbon dioxide, carbon monoxide, and temperature were within ranges anticipated for nonproblem buildings. Relative humidity was low, ranging from 11.7 to 24.0 percent. Indoor geometric mean concentrations of total volatile organic compounds (TVOCs) ranged from 73 to 235 microg/m3. The most prevalent compounds included xylene, toluene, 2-propanol, limonene, and heptane. Geometric mean formaldehyde concentrations ranged from 1.7 to 13.3 microg/m3, and mean acetaldehyde levels ranged from <3.0 to 7.5 microg/m3. Airborne concentrations of culturable bacteria and fungi were low, with no samples exceeding 150 CFU/m3. Total (direct count) bioaerosols were more variable, ranging from 5010 to 10,700 organisms/m3. Geometric mean endotoxin concentrations ranged from 0.5 to 3.0 EU/m3. Respirable particulates (PM10) were low (14 to 36 microg/m3). Noise levels ranged from 48 to 56 dBA, with mean light values ranging from 200 to 420 lux. Environmental parameters were significantly correlated with each other. The prevalence of upper respiratory symptoms (dry eyes, runny nose), central nervous system symptoms (headache, irritability), and musculoskeletal symptoms (pain/stiffness in shoulders/neck) were elevated compared to other studies using similar questionnaires. Importantly, psychosocial factors were significantly related to increased symptoms in females, while environmental factors were more closely correlated with symptoms in males. Endotoxin concentrations were associated with symptoms in both males and females. These data will help to identify and quantify the relative role of factors that contribute to sick building syndrome. The data collected in this study may also be used to evaluate the effectiveness of current building operation practices, and can be used to prioritize allocations of resources for reduction of risk associated with IEQ complaints. PMID- 11757904 TI - Mercury exposures during the recycling/reclamation of household-type alkaline batteries. PMID- 11757905 TI - Subcellular steroid/nuclear receptor dynamics. AB - Steroid hormones, thyroid hormones, retinoic acids, and vitamin D bind to their receptors, which are now called steroid/nuclear receptors, and liganded receptors translocate either intracellularly or intranuclearly and form large protein complexes with cofactors to induce or repress gene transcription. Therefore, steroid/nuclear receptors are ligand-dependent transcription factors. With the advent of green fluorescent protein (GFP) and its color variants, the subcellular distribution of many steroid/nuclear receptors has been found to be much more dynamic than previously thought, with some of the receptors shuttling between the cytoplasm and nucleus. Steroid/nuclear receptors can be divided into three categories based on their unliganded distribution: those that are primarily in the nucleus, those in the cytoplasm, and those with mixed cytoplasmic and nuclear distributions. However, in all cases, the addition of a ligand leads to almost complete nuclear translocation of the receptors. Hormonal stimulation induces intranuclear receptor distribution from a homogeneous pattern to a heterogeneous dot-like image. Ligand binding to steroid/nuclear receptors leads to the recruitment of many proteins including cofactors to provoke the redistribution of receptor complexes in the nucleus. This focal organization could involve more complex events than simple DNA binding sites for transcription. Protein activities and interactions of steroid/nuclear receptors can be imaged and localized in a single cell. PMID- 11757906 TI - Possible role of heat shock protein (Hsp) 25 in the enamel organ during amelogenesis in the rat molar. AB - The postnatal expression of heat shock protein (Hsp) 25 during the amelogenesis of rat molars was investigated by immunocytochemistry and confocal microscopy. The localization pattern of Hsp 25-immunoreactivity in the inner enamel epithelium and ameloblast cell layer of the rat molars was almost identical to that in the rat incisors which we have previously reported: an intense Hsp25 immunoreactivity, which first appeared in the preameloblasts, was recognized in secretory ameloblasts and ruffle-ended ameloblasts with stage-specific immunointensity. Confocal microscopy with Hsp 25-antibody and rhodamine-labeled phalloidin clearly demonstrated the co-localization of Hsp 25 and actin filaments in the ameloblast layer, supporting our hypothesis that this molecule might serve to reinforce the ameloblast layer during enamel formation as well as the formation and maintenance of the ruffled border in ruffle-ended ameloblasts. Interestingly, the enamel free area cells, which essentially lack the ability for enamel formation, showed the Hsp 25-immunoreactivity during 4-11 days when they developed a ruffled border, but decreased in that immunoreactivity after postnatal 15 days following apoptosis. Since Hsp 25 has been shown to be a specific inhibitor of apoptosis, the enamel-free area cells contribute to determine the outline of dentin at the cusped area. These data support our previous hypothesis on the diverse functions of Hsp 25 in amelogenesis. PMID- 11757907 TI - Novel use of bovine zeta-crystallin as a conformational DNA probe to characterize a phase transition zone and terminally differentiating fiber cells in the adult canine ocular lens. AB - Using a novel immunocytochemical staining method, we aimed to characterize the phase transition zone (PTZ) (approximatly 100 microm) in adult ocular lenses and the process of terminal differentiation (denucleation) within normal fiber cells. The binding to DNA of zeta-(zeta) crystallin (Z-DNA-binding protein) and anti double-stranded (ds-)-B-DNA antibody probes was found to decline gradually throughout denucleating fibers, with a precipitous decrease occurring at about 100 microm (PTZ). Nuclei of superficial fiber cells (in front of the PTZ) showed the highest DNA probe-binding values, followed by middle fibers (MF) and deep fibers (DF). With the use of zeta-crystallin, anti-ds-B-DNA antibody, and anti single stranded (ss-) DNA antibody probes, it was possible to reveal a loss of reactivity of fiber cell ds-DNA. Ss-DNA antibody binding was seen initially in the MF and reached its highest intensity level in the DF. The pattern of zeta crystallin probe-DNA reactivity correlates with the loss of anti-B-DNA antibody staining and decreased eosin-protein staining. These data suggest that a reorganization of DNA and intracellular protein supramolecular order in normal adult lenses occurs at a depth of about 100 microm (PTZ). PMID- 11757908 TI - Injury and repair of the soleus muscle after electrical stimulation of the sciatic nerve in the rat. AB - To study injury and subsequent changes in skeletal muscles, the rat sciatic nerve was electrically stimulated at 50 Hz and muscle contraction was induced for 30 min. Muscle damage was classified into five types (hypercontraction, hyperstretching, Z band disorders, misalignment of myofilament and regions of scarce myofilaments) by electron microscopy and quantified by ultrastructural assessment. After electrical nerve stimulation, the percentages of the injured areas of the soleus muscle were 18.8 +/- 15.8% (mean +/- SD) at 0 h, 9.7 +/- 1.0% at 6 h, 22.0 +/- 23.6% at 12 h, 13.1 +/- 3.2% at 24 h, 4.9 +/- 6.0% at 3 days and 0.5 +/- 0.4% at 7 days. At 0 h, the vast majority of ultrastructural alterations were sarcomere hypercontraction. At 6 h, hypercontraction was not recognizable and sarcomere hyperstretching and Z band disarrangement constituted the major findings. At 12 h, when the injury reached its maximum, myofilament disorganization and hyperstretching were predominant. At 24 h or afterwards, the injury began to decrease and recovered to almost normal conditions by 7 days. There were very few necrotic muscle fibers in all specimens. It is considered that the muscle lesions in the present study were reversible, and recovered through changes in various types of sarcomere alterations. Z band streaming and free ribosomes were frequently found at 12 and 24 h, which may indicate repair processes rather than newly formed lesions. PMID- 11757909 TI - Differentiation of the lingual and palatal gustatory epithelium of the rat as revealed by immunohistochemistry of alpha-gustducin. AB - We used alpha-gustducin, a taste-cell-specific G protein to investigate the onset of taste transduction and its relation to the development of the palatal and lingual taste buds. Frozen cryostat and paraffin sections were prepared from the palatal and lingual gustatory epithelium of the rat from birth till postnatal day 21 (PN 21d). At PN 1-7d, alpha-gustducin-immunoreactive solitary ovoid or bipolar cells were scattered among the oral epithelium either horizontally along the oral surface or vertically oriented between the basal lamina and oral surface. In the circumvallate and foliate papillae, these cells became wrapped in alpha-gustducin immunonegative cells surrounded by an extracellular space forming a bud-like structure. Simultaneously, different stages of typical taste buds were recognized, but alpha-gustducin was only expressed in some neonatally developed pored buds. At PN 1d, alpha-gustducin was expressed in pored taste buds with a relatively higher frequency recorded in the soft palate as compared with the nasoincisor, circumvallate, and foliate papillae. The immunoreactive cells were spindle shaped with elongated processes extending from the base to the pore of the taste buds. During the second week, the solitary cells could no longer be recognized while the total counts of immunoreactive cells within the taste buds gradually increased. We argue that taste transduction is essentially required from the time of birth and can be fulfilled by both of the solitary chemosensory cells, which are immunoreactive for alpha-gustducin and scattered in the oral epithelium, and the taste cells within the mature taste buds. Moreover, the onset of taste transduction accomplished by the palatal taste buds developed earlier than that achieved by taste buds in the circumvallate and foliate papillae. PMID- 11757910 TI - Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA in trophoblast and endometrial epithelial cell populations of the synepitheliochorial placenta of goats (Capra hircus). AB - Membrane-type 1 matrix metalloproteinase (MT1-MMP), a membrane-bound matrix metalloproteinase, plays crucial roles in cellular migration through the matrix during embryogenesis, wound healing, and the invasion of host tissues by cancer cells. Mammalian trophoblast cells exhibit different degrees of invasiveness towards the endometrium in different species during gestation. The highly invasive trophoblast cells of primates and rodents which form hemochorial placentae have often been compared to metastatic cancer cells, and are known to express MT1-MMP at their invasive edge. So far, however, little is known about MT1-MMP expression in the placenta of non-invasive type including the synepitheliochorial placenta of bovidae. As an approach to assess the role played by MT1-MMP in the non-invasive synepitheliochorial placentation, we determined the open reading frame (ORF) base sequence of caprine MT1-MMP (DDBJ/EMBL/GenBank database: AB010921); this sequence is the first registered MT1-MMP ORF sequence of artyodactyls which develop placentae of the non-invasive type. The deduced amino acid sequence of caprine MT1-MMP exhibited 92, 87 and 89% identity with its human, mouse and rat counterparts, respectively. Availability of the cloned caprine MT1-MMP cDNA allowed us to carry out Northern blot analysis which revealed that in the placentome, the expression levels of MT1-MMP mRNA were very low on Day 35 of gestation (peri-implantation stage), while the levels gradually increased from Day 75 to Day 100. In the interplacentome regions of the placenta and the uterus, the signal levels were higher than those in the placentome, and increased from Day 35 onward, peaking on Day 75. In situ hybridization experiments revealed that the binucleate trophoblast cells reacted with the MT1 MMP cRNA probe throughout the period examined while the uninuclear principal trophoblast cells did so only on Day 100. Of particular interest is the expression of MT1-MMP transcripts in the luminal and glandular epithelial cells of the gestational endometrium, since epithelial cells in general have been noted to lack MMP expression, including MT-MMPs. The high levels of MT1-MMP expression in the endometrial epithelial cell populations might reflect extensive remodeling during gestation. PMID- 11757911 TI - Alteration in the expression of heat shock protein (Hsp) 25-immunoreactivity in the dental pulp of rat molars following tooth replantation. AB - The regeneration process of dental pulp following tooth replantation in rat molars was investigated by immunocytochemistry for heat shock protein (Hsp) 25 and protein gene product 9.5 (PGP 9.5). In control teeth at postnatal 4 weeks, the odontoblasts showed intense Hsp 25-immunoreactivity in the coronal dental pulp, but little or no immunoreactivity in the root and floor pulp. In contrast, the Hsp 25-negative odontoblasts in the latter areas displayed immunoreactivity for PGP 9.5. Tooth replantation caused loss of Hsp 25- and PGP 9.5 immunoreactions in the dental pulp during postoperative days 1-3. At postoperative day 5, plump cells with clear nucleoli and several fine processes- presumably newly differentiated odontoblasts--at the pulp-dentin border became immunopositive for Hsp 25. These data suggest that the expression of Hsp 25- and PGP 9.5-immunoreactivity reflects the status of differentiation of the odontoblasts. Furthermore, some pulpal nerve fibers as well as the Schwann cells in the dental pulp, ordinarily negative in Hsp 25-immunoreaction, acquired their immunoreactivity by postoperative day 5, but lost it thereafter, suggesting the involvement of Hsp 25 in the regeneration of pulpal nerve fibers. In the case of bone-like tissue formation in the pulp space, on the other hand, no Hsp 25 immunoreactive odontoblasts were recognized in the pulp-dentin border. Thus, the alignment of Hsp 25-immunopositive odontoblasts along the pulp-dentin border indicates a decisive factor for inducing the reparative dentin formation after tooth replantation. PMID- 11757912 TI - Biliary tract of the rat as observed by scanning electron microscopy of cast samples. AB - The three-dimensional distribution of the biliary tract in the rat was studied by scanning electron microscopy of biliary casts. The casts were prepared by a retrograde infusion of a low viscosity or monomeric methacrylate resin mixture into the common bile duct. No resin flow from the bile canaliculi to sinusoidal capillaries was ever noted. Bile canaliculi formed intricate meshworks and drained via the Hering's canals into the bile ductules. The bile canalicular meshworks of adjacent lobules intercommunicated with each other. The bile ductules formed a marked periportal plexus around the portal vein branch, and drained into the intrahepatic bile duct running along the portal vein branch. The junctional zone of the Hering's canal and bile ductule usually showed an ampullary dilation. When the Hering's canal directly drained into a thick bile ductule or into a periportal plexus of bile ductules, such an ampullary dilation at the origin of the bile ductule was never replicated. The extrahepatic bile duct protruded many crypt-like projections which presumably corresponded to parietal glands. It is suggested that the periportal plexus of bile ductules may store the bile as a substitute for the gallbladder. PMID- 11757913 TI - Cellular localization of the diazepam binding inhibitor (DBI) in the gastrointestinal tract of mice and its coexistence with the fatty acid binding protein (FABP). AB - The diazepam binding inhibitor (DBI), initially isolated as an endogenous 10-kDa polypeptide from the brain, has the ability to displace ligands from benzodiazepine binding sites on gamma-aminobutyric acid (GABA) receptors. However, DBI is widely distributed outside the brain, with the highest expression in the intestine. The present in situ hybridization study revealed the cellular expression of DBI mRNA throughout the gastrointestinal tract of mice, showing it to be intensely expressed in the spinous layer in the stratified squamous epithelium of the oral cavity, esophagus and forestomach, in surface mucous cells in the glandular stomach, and in columnar (absorptive) cells of the intestinal villi. A precise identification of DBI-expressing cell types was confirmed immunohistochemically, although the expressing cells detectable by the two histochemical methods differed slightly in their extension. Noteworthily, DBI always coexisted with the fatty acid binding protein (FABP), which participates in the uptake and metabolic processing of long chain fatty acids. In addition to the biochemical finding that DBI is identical with the acyl-CoA binding protein (ACBP), the distributional patterns of DBI and its colocalization with FABPs suggests its involvement in the absorption and metabolism of lipid in the epithelia of the digestive tract. PMID- 11757914 TI - Annihilation of shocks in forced oscillations of an air column in a closed tube. PMID- 11757915 TI - The effect of exit radii on intraglottal pressure distributions in the convergent glottis. PMID- 11757916 TI - Evaluation of a fundamental integral in rough-surface scattering theory. AB - An algorithm is presented for the numerical evaluation of a fundamental but intractable integral that occurs in the physical theory of scattering from random rough surfaces. It is based on a rational-function approximation to an integrand factor, augmented with techniques for excluding poles and zeros from the path of integration. Examples, complete with error analysis, are provided for cases relevant to acoustic sea-floor and sea-surface scattering. PMID- 11757917 TI - An effective density fluid model for acoustic propagation in sediments derived from Biot theory. AB - In this paper we present an acoustic propagation model that approximates a porous medium as a fluid with a bulk modulus and effective density derived from Biot theory. Within the framework of Biot theory it is assumed here that the porous medium has low values of frame bulk and shear moduli relative to the other moduli of the medium and these low values are approximated as zero. This leads to an effective density fluid model. It is shown that, for saturated sand sediments, the dispersion, transmission, reflection, and in-water backscattering predicted with this effective density fluid model are in close agreement with the predictions of Biot theory. In this agreement we demonstrate that the frame bulk and shear moduli play only a minor role in determining several aspects of sand acoustics. Thus, for many applications the effective density fluid model is an accurate alternative to full Biot theory and is much simpler to implement. PMID- 11757918 TI - Simplified method to solve sound transmission through structures lined with elastic porous material. AB - An approximate analysis method is developed to calculate sound transmission through structures lined with porous material. Because the porous material has both the solid phase and fluid phase, three wave components exist in the material, which makes the related analysis very complicated. The main idea in developing the approximate method is very simple: modeling the porous material using only the strongest of the three waves, which in effect idealizes the material as an equivalent fluid. The analysis procedure has to be conducted in two steps. In the first step, sound transmission through a flat double panel with a porous liner of infinite extents, which has the same cross sectional construction as the actual structure, is solved based on the full theory and the strongest wave component is identified. In the second step sound transmission through the actual structure is solved modeling the porous material as an equivalent fluid while using the actual geometry of the structure. The development and validation of the method are discussed in detail. As an application example, the transmission loss through double walled cylindrical shells with a porous core is calculated utilizing the simplified method. PMID- 11757919 TI - Coupled guided acoustic modes in water-filled thin-walled tubes. AB - Recent results [J. D. N. Cheeke et al., J. Acoust. Soc. Am. 104, 3678 (1998)] reported a 20% decrease in group velocity for flexural mode circumferential waves propagating around water-filled thin-walled stainless-steel tubes. In the present work, the full theory of such modes is developed to explain the structure modes which originates from the coupling between the water filler and stainless tube. Calculated values of the group velocity for the first two coupled modes are in excellent agreement with experiment. The results are of interest for the physics of acoustic waves in fluid-loaded structures and have potential application for liquid level detection. PMID- 11757920 TI - Theoretical and experimental study of the influence of the particle size distribution on acoustic wave properties of strongly inhomogeneous media. AB - The ultrasonic method is particularly suitable to characterize diffusive media, as acoustic properties (velocity and attenuation) are related to the properties and concentrations of the homogeneous phase and scatterers. Thus, ultrasonic characterization can be useful in the study of sedimentation or flocculation processes, in concentration measurements, and granulometry evaluation. Many models have been developed for media where particles are very small compared to the incident wavelength. When the diameter of the particles is close to the wavelength, multiple-scattering theories have to be used to describe the propagation of waves. In this paper, the case where the ratio of wavelength to scatterer size is around unity is studied. First, the particle size distribution is taken into account in two types of multiple-scattering theories based on the effective field approximation or on the quasicrystalline approximation and theoretical results are produced. The T-matrix formalism has been used to calculate the amplitude of the wave scattered by a single sphere. The calculation of the complex wave number in the effective medium has been implemented, using in particular the Percus-Yevick equation as a spatial pair-correlation function between scatterers, and a normal particle-size distribution. The influence of these parameters is discussed. Finally, attenuation and phase velocity measurements are performed in moving suspensions of acrylic spheres in ethylene glycol, at various concentrations and for different particle-size distributions. A good agreement between the theoretical results and the measurements is found for both velocity and attenuation. These results show that the size distribution is a critical parameter to understand velocity and attenuation behavior as function of frequency and volume fraction. PMID- 11757921 TI - Acoustic flowmeter for the measurement of the mean flow velocity in pipes. AB - This paper proposes a new technique for measuring the gas flow velocity averaged along the finite length of a pipe as well as over its cross-sectional area. Unlike the conventional gas flowmeters, the proposed technique exploits the one dimensional plane waves that propagate uniformly across the pipe cross-sectional area. When a fluid flows along the pipe, the plane waves are superposed with the flow field such that the positive-going and negative-going plane wave components undergo the change of their wave numbers. Such wave number variation due to the mean flow velocity has provided a major motivation for developing a new way of measuring the mean flow velocity in the pipe, which is referred to as the acoustic flowmeter. To examine the feasibility of the developed flow velocity measurement method, including its theoretical backgrounds, experimental setups are illustrated in this paper. Detailed experimental data for the flow velocity range of 2-27 m/s reveal the linearity of the proposed acoustic flowmeter and its salient environmental robustness for the different acoustic pressure patterns in the pipe and, furthermore, for different velocity profiles over the pipe cross section area. PMID- 11757922 TI - Some aspects of sound extinction by zooplankton. AB - To address the importance of sound extinction (or the shadowing effect) in the presence of a densely aggregated zooplankton layer, acoustic scattering by weakly scattering fluid objects is studied theoretically. An analytical expression for the extinction cross section is obtained based on the forward scattering theorem and the analytical formula for the forward scattering amplitude is derived from the Modal Based-Deformed Cylinder Model (MB-DCM). The validity of the MB-DCM solution for the forward scattering amplitude and its sensitivity to geometrical and physical parameters is studied. Comparison with the PC-DWBA (Phase Compensated-Distorted Wave Born Approximation) shows a reasonable agreement between the two models. The extinction cross section is shown to be proportional to (ka)2 and the induced attenuation is predicted for various species of zooplankton over a wide frequency range. It is shown that, under certain realistic conditions, such as the presence of a swarm of aggregated krill, sound extinction by zooplankton could influence the acoustic measurements significantly, as much as an 85% reduction in acoustic intensity for Euphausia superba with n = 5000 ind./m3 over a range of 50 m. PMID- 11757923 TI - Visualization of pass-by noise by means of moving frame acoustic holography. AB - The noise generated by pass-by test (ISO 362) was visualized. The moving frame acoustic holography was improved to visualize the pass-by noise and predict its level. The proposed method allowed us to visualize tire and engine noise generated by pass-by test based on the following assumption; the noise can be assumed to be quasistationary. This is first because the speed change during the period of our interest is negligible and second because the frequency change of the noise is also negligible. The proposed method was verified by a controlled loud speaker experiment. Effects of running condition, e.g., accelerating according to ISO 362, cruising at constant speed, and coasting down, on the radiated noise were also visualized. The visualized results show where the tire noise is generated and how it propagates. PMID- 11757924 TI - Pulse response of a nonlinear layer. AB - A simple analytical theory is developed for the description of the non-steady state response of a thin nonlinear layer, which differs markedly in its linear properties from the surrounding medium. Such a layer can model the behavior of real inhomogeneities like a cloud of gas bubbles in a liquid, a crack or split plane in a solid, or the contact between two slightly tightened rough surfaces. Both weakly nonlinear pulse and harmonic responses are calculated and the general properties of the spectral and temporal structures of the scattered field are discussed. Exact strongly nonlinear solutions are derived for a special type of stress-strain relationship corresponding to the behavior of real condensed media under strong loads. Profiles and spectra shown conform with experimental results. The pulse response on the short delta-pulse shaped incident wave is calculated for arbitrary nonlinear properties of the layer. The possibilities to apply the sets of data on measured characteristics of pulse response in the solution of inverse problems are briefly discussed. PMID- 11757925 TI - Detection and monitoring of cracks using mechanical impedance of rotor-bearing system. AB - The dynamic behavior of structures, in particular, that of a rotor, containing cracks is a subject of considerable current interest. In the present study, the influence of a transverse surface crack, both open and breathing conditions, on the mechanical impedance of the rotor-bearing system, has been investigated by FEM analysis for flexural vibrations. The results show that the mechanical impedance changes substantially due to the presence of crack and follow definite trends with the crack parameters (depth and location) and force location. The normalized mechanical impedance of rotor system is more sensitive to the breathing crack when compared to the open crack. The sudden changes in mechanical impedance have been observed at the multiples of the running frequency for the breathing crack. The measurement of mechanical impedance has been suggested for crack detection and condition monitoring of rotor-bearing systems. PMID- 11757926 TI - An experimental study of the impedance of perforated plates with grazing flow. AB - An experimental investigation of the linear impedance of perforated interfaces exposed to grazing fluid flow is presented, including a description of the branch type setup used in the study. The experimental setup employs a movable microphone in the branch duct that improves the error characteristics of the system. The impedance parameters of three perforated samples have been measured including one circular, square-edged orifice and two production muffler louver geometries. The data are presented in terms of the equivalent length and resistance of the samples, with the friction velocity being used to characterize the grazing flow. At higher grazing flow velocities, the equivalent length of each sample decreased by an amount representative of the Rayleigh end correction for one side of an orifice. Resistance for the louvers appears to be somewhat less sensitive to grazing flow than the circular orifice, though all of the samples showed significant increases. While the experimental results for all three samples showed similar basic trends, distinct and substantial differences were observed between each perforate geometry. PMID- 11757927 TI - The acoustic properties of granular materials with pore size distribution close to log-normal. AB - The majority of realistic porous materials are composed of pores of which the shape is variable and the size of the pores normally obeys a distinctive statistical distribution. Although the variation of pore shape is less important, the statistical parameters of pore size distribution can have a considerable effect on the acoustic properties of porous media. This paper discusses the application of a simple model for the prediction of the acoustic properties of porous granular media with some assumed pore geometry and pore size distribution close to log-normal. The model is based on the rational (Pade) approximation approach [K. V. Horoshenkov, K. Attenborough, and S. N. Chandler-Wilde, J. Acoust. Soc. Am. 104, 1198-1209 (1998)] which has been developed for some simple pore geometries. It is shown that the experimentally determined pore size distribution for a representative range of granular materials is often close to log-normal. This assumption enables accurate predictions of the acoustic performance of these materials using the presented model. The water suction method is proposed to determine the parameters of the log-normal distribution, which are the mean pore size, (phi) and its standard deviation, sigma. This method is nonacoustic, modelless and well-adapted to acoustic materials and, unlike the BET method [S. Brunauer, P. H. Emmett, and E. Teller, J. Am. Chem. Soc. 60, 309-319 (1938)], is easy to reproduce in any basic acoustic laboratory requiring no expensive parts or chemicals. The proposed Pade approximation is based entirely on four measurable nonacoustic parameters, the porosity, omega, flow resistivity, Rb, tortuosity, q2 and the standard deviation of the pore size, sigma. The method is successfully tested on a representative selection of consolidated and nonconsolidated porous granular materials. PMID- 11757928 TI - Efficient prediction methods for the micro-pressure wave from a high-speed train entering a tunnel using the Kirchhoff formulation. AB - The compression wave generated by a high-speed train emerging from the exit portal of a tunnel gives rise to an impulsive noise called a micro-pressure wave. In this study, new methods for the prediction of sonic-boom noise are proposed. The first method combines acoustic monopole analysis and the method of characteristics with the Kirchhoff method. The compression wave from a train entering a tunnel is calculated by an approximate compact Green's function, and the resultant noise at the tunnel exit is predicted by a linear Kirchhoff formulation. The second method couples the Kirchhoff formulation with the Euler equation, which is solved numerically for the generation and propagation of the compression wave. Numerical prediction of the compression wave, the propagation in the tunnel, and the micro-pressure wave obtained by the present methods are compared with measured data. The numerical results exhibit a reasonable agreement with the experimental data. The proposed methods in this study are shown to be very useful design tools for the nose shape of trains and the geometry of tunnels, and they can be utilized to minimize the pressure fluctuation in the tunnel and the corresponding booming noise. PMID- 11757929 TI - Evaluation of loudness-level weightings for assessing the annoyance of environmental noise. AB - Assessment of the annoyance of combined noise environments has been the subject of much research and debate. Currently, most countries use some form of the A weighted equivalent level (ALEQ) to assess the annoyance of most noises. It provides a constant filter that is independent of sound level. Schomer [Acust. Acta Acust. 86(1), 49-61 (2000)] suggested the use of the equal loudness-level contours (ISO 226, 1987) as a dynamic filter that changes with both sound level and frequency. He showed that loudness-level-weighted sound-exposure level (LLSEL) and loudness-level-weighted equivalent level (LL-LEQ) can be used to assess the annoyance of environmental noise. Compared with A-weighting, loudness level weighting better orders and assesses transportation noise sources, sounds with strong low-frequency content and, with the addition of a 12-dB adjustment, it better orders and assesses highly impulsive sounds vis-a-vis transportation sounds. This paper compares the LLSEL method with two methods based on loudness calculations using ISO 532b (1975). It shows that in terms of correlation with subjective judgments of annoyance-not loudness-the LLSEL formulation performs much better than do the loudness calculations. This result is true across a range of sources that includes aircraft, helicopters, motor vehicles, trains, and impulsive sources. It also is true within several of the sources separately. PMID- 11757930 TI - Mechanism of sound absorption by seated audience in halls. AB - Four methods are explored for predicting the reverberation times in fully occupied halls for music as related to the sound absorption by their audiences. The methods for providing audience absorptions include two that use reverberation chambers, namely, the ISO 354 method (and other similar standards) (ISO) and Kath and Kuhl's method (K & K) [Acustica 15, 127-131 (1965)], and two that use average data from halls, i.e., Beranek's method (COH) [Concert and Opera Halls: How They Sound (Acoustical Society of America, Melville, NY, 1996)], and the average audience power-per-seat absorption which in practice is multiplied by the number of seats (AA). These methods are applied to the calculation of reverberation times in six existing halls, fully occupied, and the results were compared with actual measurements. The COH method was best for predictions over the entire frequency range. The K & K method showed the highest accuracy at mid-frequencies. Both the ISO and the K & K methods yielded wide differences for the measurements in the 125- and 250-Hz bands. The AA method was as good as the COH method when the measurements for the six halls were averaged, but showed a wide spread in the predictions around the average because it does not consider the degree of upholstering of the seats. It was hypothecated by the authors that the principal reasons for the ISO and K & K discrepancies at low frequencies were (a) differences between the degree of sound diffusion in actual halls and that in reverberation chambers, and (b) lack of information on the mechanisms of absorption of sound by people seated side-by-side in rows, particularly for near grazing incidence sound fields. First, this article explores the sound diffusivity in a reverberation chamber and in the halls using CAD models. A probability density function of the incident angles of the sound rays that impinge on the audiences is defined and was measured for each case. Using a unique method, the sound absorption coefficient of each portion of the body and chair in a seated audience was determined in an anechoic chamber as a function of the incident angle of a sound wave. With adjustments from these findings, the K & K method can be made to equal the COH method in accuracy at all frequencies. Its forte is that it can be used for the determination of the sound absorption of occupied chairs from measurements of a limited number in a reverberation chamber. PMID- 11757931 TI - Instantaneous frequency and short term fourier transforms: application to piano sounds. AB - For more than 30 years and until nowadays, development of a system reproducing the functioning of human hearing has remained an aim difficult to reach. Recent methods for identification of the fundamental frequency of musical sounds obtain good results using information about the temporal evolution of the amplitude and frequency of individual sound partials. Piano sounds and polyphonic sounds, which can have several partials that are closely spaced in the frequency domain, have not been extensively tested by these procedures. In this paper, the Instantaneous Frequency (IF), as defined by the Hilbert transform, is used to obtain the frequency variations of piano sounds partials. The result implies that, for these sounds, the IF may contain modulations resulting in the separation of an apparent single sinusoid signal into two or more sinusoidal components at various times in the analysis process, which makes it impossible to use the temporal evolution of the frequency of partials for the procedure of note identification. The separation phenomenon also appears when the short term Fourier transform is used and can induce the detection of short-lived parasitic spectral peaks that must be taken into account by any note identification procedure based on the use of spectral information. PMID- 11757932 TI - On representing signals using only timing information. AB - It is well known that only a special class of bandpass signals, called real-zero (RZ) signals can be uniquely represented (up to a scale factor) by their zero crossings, i.e., the time instants at which the signals change their sign. However, it is possible to invertibly map arbitrary bandpass signals into RZ signals, thereby, implicitly represent the bandpass signal using the mapped RZ signal's zero crossings. This mapping is known as real-zero conversion (RZC). In this paper a class of novel signal-adaptive RZC algorithms is proposed. Specifically, algorithms that are analogs of well-known adaptive filtering methods to convert an arbitrary bandpass signal into other signals, whose zero crossings contain sufficient information to represent the bandpass signal's phase and envelope are presented. Since the proposed zero crossings are not those of the original signal, but only indirectly related to it, they are called hidden or covert zero crossings (CoZeCs). The CoZeCs-based representations are developed first for analytic signals, and then extended to real-valued signals. Finally, the proposed algorithms are used to represent synthetic signals and speech signals processed through an analysis filter bank, and it is shown that they can be reconstructed given the CoZeCs. This signal representation has potential in many speech applications. PMID- 11757933 TI - Boundary element method calculation of individual head-related transfer function. I. Rigid model calculation. AB - Human spatial perception of sound is a complex phenomenon. The Head-Related Transfer Function (HRTF) is a vital component to spatial sound perception. In order improve the understanding of the correlation between the HRTF and specific geometry of the head and pinna, a Boundary Element Method (BEM) has been used to calculate a portion of the HRTF of an individual based on precise geometrical data. Advantages of this approach include the ability to alter the geometry of the individual through the model in ways which are not possible with real subjects. Several models are used in the study, including a head with no pinna and several sized spheres. Calculations are performed for various source locations around the head. Results are presented for rigid model cases. Effects of variations on impedance and comparisons to measured data will be presented in the subsequent paper. PMID- 11757934 TI - Boundary element method calculation of individual head-related transfer function. II. Impedance effects and comparisons to real measurements. AB - Following previous work by the author involving the calculation of an individual head-related transfer function (HRTF) using a Boundary Element Method (BEM) approach, impedance conditions are now included to take account of the acoustic properties of human hair. In addition, comparisons are made here between calculations and measured values for the HRTF of a specific individual. Numerous works have been published regarding the measurement of HRTFs, but rarely are several methods compared for the same individual. The results presented in the work compare two different measurement techniques and a computational BEM for acquiring an individual HRTF. Impedance effects have been incorporated in the BEM model for hair based on measured data, providing a final set for comparison. Measurement results show significant variations for the same individual. Computational results show good agreement within the range of experimental variations. Definite trends are observed for many directions, while the limitations of the methods are also highlighted for others. The effects of incorporating hair impedance are shown to provide an improvement in the correlation of computational results, indicating an affect of hair impedance on the HRTF. PMID- 11757935 TI - Distortion-product otoacoustic emissions measured at high frequencies in humans. AB - Distortion-product otoacoustic emissions (DPOAEs) elicited with stimulus frequencies less than or equal to 8 kHz have been used in hearing clinics to assess whether the middle ear and cochlea are normal, but high-frequency hearing (>4 kHz) is most vulnerable to cochlear pathology. It might prove useful to measure DPOAEs with even higher frequency stimuli (>8 kHz), but there have been few reports of such studies in humans. DPOAEs have been measured in other mammals to the upper range of hearing sensitivity. The purpose of this study was to compare some characteristics of DPOAEs in human subjects elicited with high frequency stimuli with those that have been extensively measured with lower frequency stimuli. The primary goal was to establish if the same phenomenon responsible for the behavior of low-frequency DPOAEs is responsible for the behavior of high-frequency DPOAEs. Specifically, the DPOAE level with stimuli varied from 2 to 20 kHz, growth functions of DPOAEs, effects of varying the primary frequency ratio (f2/f1) on the DPOAE level, and DPOAE group delay were determined. Because the behaviors appeared to vary smoothly with stimulus frequency, the study suggests that emissions measured from 2 to 20 kHz were the product of the same biological process. PMID- 11757936 TI - Second-order modulation detection thresholds for pure-tone and narrow-band noise carriers. AB - Modulation perception has typically been characterized by measuring detection thresholds for sinusoidally amplitude-modulated (SAM) signals. This study uses multicomponent modulations. "Second-order" temporal modulation transfer functions (TMTFs) measure detection thresholds for a sinusoidal modulation of the modulation waveform of a SAM signal [Lorenzi et al., J. Acoust. Soc. Am. 110, 1030-2038 (2001)]. The SAM signal therefore acts as a "carrier" stimulus of frequency fm, and sinusoidal modulation of the SAM signal's modulation depth (at rate f'm) generates two additional components in the modulation spectrum at fm - f'm and fm + f'm. There is no spectral energy at the envelope beat frequency f'm in the modulation spectrum of the "physical" stimulus. In the present study, second-order TMTFs were measured for three listeners when fm was 16, 64, and 256 Hz. The carrier was either a 5-kHz pure tone or a narrow-band noise with center frequency and bandwidth of 5 kHz and 2 Hz, respectively. The narrow-band noise carrier was used to prevent listeners from detecting spectral energy at the beat frequency f'm in the "internal" stimuli's modulation spectrum. The results show that, for the 5-kHz pure-tone carrier, second-order TMTFs are nearly low pass in shape; the overall sensitivity and cutoff frequency measured on these second order TMTFs increase when fm increases from 16 to 256 Hz. For the 2-Hz-wide narrow-band noise carrier, second-order TMTFs are nearly flat in shape for fm = 16 and 64 Hz, and they show a high-pass segment for fm = 256 Hz. These results suggest that detection of spectral energy at the envelope beat frequency contributes in part to the detection of second-order modulation. This is consistent with the idea that nonlinear mechanisms in the auditory pathway produce an audible distortion component at the envelope beat frequency in the internal modulation spectrum of the sounds. PMID- 11757937 TI - Perceptual fusion and fragmentation of complex tones made inharmonic by applying different degrees of frequency shift and spectral stretch. AB - Global pitch depends on harmonic relations between components, but the perceptual coherence of a complex tone cannot be explained in the same way. Instead, it has been proposed that the auditory system responds to a common pattern of equal spacing between components, but is only sensitive to deviations from this pattern over a limited range [Roberts and Brunstrom, J. Acoust. Soc. Am. 104, 2326-2338 (1998)]. This hypothesis predicts that spectral fusion will be largely unaffected either by frequency shifting a harmonic stimulus (because equal spacing is preserved), or by small degrees of spectral stretch (because significant deviations from equal spacing only cumulate over large spectral distances). Complex tones were either shifted by 0%-50% of F0 (200 Hz+/-10%) or stretched by 0%-12% of F0 (100 Hz+/-10%). Subjects heard a complex followed by a pure tone in a continuous loop. One of the components 2-11 was mistuned by +/- 4%, and subjects adjusted the pure tone to match its pitch. Broadly consistent with our hypothesis, frequency shifts had relatively little effect on hit rates and only large degrees of stretch reduced them substantially. The implications for simultaneous grouping are explored with reference to an autocorrelation model of auditory processing. PMID- 11757938 TI - Sources of variation in profile analysis. I. Individual differences and extended training. AB - This study investigated two sources of variance in the ability to discriminate auditory profiles: individual differences and extended training. The goals of the study were (1) to determine the range and origins of individual differences in profile analysis and (2) to determine whether those who initially had poor sensitivity to changes in spectral shape could eventually acquire finer sensitivity. Profile stimuli had 11 components with equal-log spacing from 200 2200 Hz. Thresholds ranged from - 1 to -25 dB (signal level relative to the context level) across 46 listeners. The correlation between spectral-shape discrimination thresholds after 2000 trials and pure-tone intensity discrimination thresholds was 0.36. The range of individual differences for pure tone intensity discrimination and spectral-shape discrimination was about the same. Two groups of listeners were given extended practice on the profile task, one group that showed low thresholds after an initial 2000 trials of practice and another that showed much higher initial thresholds. All listeners improved during the course of the first 2000 trials of training. Most of the poor listeners continued to improve during 9000 trials of training. Individual differences in the listeners' sensitivity to changes in spectral shape still existed after the extended practice. PMID- 11757939 TI - Sources of variation in profile analysis. II. Component spacing, dynamic changes, and roving level. AB - Profile-analysis experiments have typically employed static profiles with constant frequency components spaced at equal intervals along a logarithmic frequency axis. Most periodic, naturally occurring stimuli, however, have components that are harmonically related and vary dynamically in time. One goal of these studies was to determine whether amplitude-increment detection thresholds are different in dynamic, harmonically spaced profiles compared to those for static-log profiles, and why such differences might exist. A second goal was to determine the impact of roving levels (within-trial variation of level). Thresholds for static-log profiles were, on average, 8.7 dB lower than for static-harmonic profiles. A traditional filter-bank model could not account for this result. No consistent effect of dynamic contour (an exponential rising frequency glide) was observed. Thresholds were consistently poorer by 4 to 7 dB when the level was roved, but the differences in thresholds among the different profiles varied little. It is proposed that the higher thresholds observed in static-harmonic profiles may be accounted for by the more intense pitch strength associated with the harmonic profiles. PMID- 11757940 TI - The intensity-difference limen for Gaussian-enveloped stimuli as a function of level: tones and broadband noise. AB - Van Schijndel et al. [J. Acoust. Soc. Am. 105, 3425-3435 (1999)] have proposed that the internal excitation evoked by an auditory stimulus is segmented into "windows" according to the stimulus spectrum and stimulus length. This "multiple looks" model accounts for the mid-duration hump they observed in plots of intensity-difference limens (DLs) versus pip duration for Gaussian-shaped 1- and 4-kHz tones, an effect replicated by Baer et al. [J. Acoust. Soc. Am. 106, 1907 1916 (1999)]. However, van Schijndel et al. and Baer et al. used few levels. A greater number of levels were used by Nizami (1999) for Gaussian-shaped 2-kHz tone-pips whose equivalent rectangular duration (D) was 1.25 ms. The DLs show the mid-level hump known for clicks [Raab and Taub, J. Acoust. Soc. Am. 46, 965-968 (1969)]. At some duration this pattern must become the "near-miss to Weber's law." To determine this duration, as well as the level-dependence of the mid duration hump, DLs were established for Gaussian-shaped 2-kHz tone-pips of D = 1.25, 2.51, and 10.03 ms at levels of 30-90 dB SPL. The across-subject average DLs for the tone-pips rise up at mid-levels for D= 1.25 and D = 2.51 ms. The DLs for D=2.51 ms are larger, creating the mid-duration hump. At all durations, the new DLs are smaller at high levels than at low levels, consistent with the near miss to Weber's law. DLs were also obtained here for Gaussian-shaped broadband noise pips of D=0.63, 1.25, 2.51, 5.02, and 10.03 ms. The DLs for the noise-pip show a mid-level hump for all pip durations. The noise-pip DLs decrease as the pip lengthens, such that the plot of DL versus log duration shows a linear decline, with no mid-duration hump. Analysis of variance reveals that the mid level hump coexists with the classical patterns of level-dependence, perhaps reflecting the existence of two level-encoding mechanisms, one that depends on firing-rates counted over single neurons and which is responsible for the classical patterns, and one that depends on the initial coordinated burst of neuronal spikes caused by rapid ramping, and which presumably causes the mid level hump. PMID- 11757941 TI - The variation across time of sensitivity to interaural disparities: behavioral measurements and quantitative analyses. AB - Zurek (1980) measured listeners' sensitivities to interaural disparities conveyed by a 5-ms "probe" segment embedded within a 50-ms burst of otherwise diotic broadband noise [P. M. Zurek, J. Acoust. Soc. Am. 67, 952-964 (1980)]. He found that thresholds for interaural time delay (ITD) and interaural intensitive difference (IID) were markedly elevated when the onset of the probe segment occurred between 1 and 5 ms after the onset of the burst. Zurek postulated that this occurred because the leading portion of the noise briefly inhibited sensitivity to subsequent binaural information. If such inhibition were the primary factor responsible for the elevation in thresholds, then the omission of the portion of the noise trailing the probe segment would be expected to have little, if any, influence on performance. In order to test this hypothesis, listeners' sensitivities to ITD and IID were measured using a paradigm similar to that employed by Zurek. The results revealed that the omission of either the leading or the trailing portions of the diotic noise led to substantial reductions in threshold ITDs and IIDs. The data were successfully accounted for by a model based upon a combination of a temporal window with an equivalent rectangular duration of approximately 10 ms and a weighting function representing a brief loss of binaural sensitivity just after the onset of a sound. PMID- 11757942 TI - Informational and energetic masking effects in the perception of multiple simultaneous talkers. AB - Although many researchers have examined the role that binaural cues play in the perception of spatially separated speech signals, relatively little is known about the cues that listeners use to segregate competing speech messages in a monaural or diotic stimulus. This series of experiments examined how variations in the relative levels and voice characteristics of the target and masking talkers influence a listener's ability to extract information from a target phrase in a 3-talker or 4-talker diotic stimulus. Performance in this speech perception task decreased systematically when the level of the target talker was reduced relative to the masking talkers. Performance also generally decreased when the target and masking talkers had similar voice characteristics: the target phrase was most intelligible when the target and masking phrases were spoken by different-sex talkers, and least intelligible when the target and masking phrases were spoken by the same talker. However, when the target-to-masker ratio was less than 3 dB, overall performance was usually lower with one different-sex masker than with all same-sex maskers. In most of the conditions tested, the listeners performed better when they were exposed to the characteristics of the target voice prior to the presentation of the stimulus. The results of these experiments demonstrate how monaural factors may play an important role in the segregation of speech signals in multitalker environments. PMID- 11757943 TI - High-speed digital imaging of the medial surface of the vocal folds. AB - High-speed digital imaging of the medial surface of the vocal folds was performed in excised canine larynx experiments. Building on the excised larynx investigations of Baer [Ph.D. dissertation, MIT, Boston, MA (1975)] and hemilarynx investigations of Jiang and Titze [Laryngoscope 103, 872-882 (1993)], nine vocal fold fleshpoints were tracked simultaneously along the medial surface of one coronal plane of the left vocal fold using a Kodak EktaPro 4540 high-speed digital imaging system. By imaging from two distinct views, 3D reconstructions of fleshpoint trajectories were performed with a sampling frequency of 4.5 kHz and a spatial resolution of approximately 0.08 mm. Quantitative results were derived from a typical example of periodic chestlike vibrations. Furthermore, these data were decomposed into empirical eigenfunctions, the building blocks of vocal fold vibration, illuminating basic mechanisms of self-sustained oscillation. Previously, such mechanisms have only been explored theoretically using computer models of vocal fold vibration [Berry et al., J. Acoust. Soc. Am. 95, 3595-3604 (1994)]. Similar to the theoretical studies, two eigenfunctions captured 98% of the variance of the data. Because this investigation utilized high-speed technology, the methodology may also be used to examine complex, aperiodic vibrations. Thus, this technique allows mechanisms of regular and irregular vocal fold vibration to be explored using direct observations of vibrating tissues in the laboratory. PMID- 11757944 TI - Aero-acoustics of silicone rubber lip reeds for alternative voice production in laryngectomees. AB - To improve voice quality after laryngectomy, a small pneumatic sound source to be incorporated in a regular tracheoesophageal shunt valve was designed. This artificial voice source consists of a single floppy lip reed, which performs self sustaining flutter-type oscillations driven by the expired pulmonary air that flows through the tracheoesophageal shunt valve along the outward-striking lip reed. In this in vitro study, aero-acoustic data and detailed high-speed digital image sequences of lip reed behavior are obtained for 10 lip configurations. The high-speed visualizations provide a more explicit understanding and reveal details of lip reed behavior, such as the onset of vibration, beating of the lip against the walls of its housing, and chaotic behavior at high volume flow. We discuss several aspects of lip reed behavior in general and implications for its application as an artificial voice source. For pressures above the sounding threshold, volume flow, fundamental frequency and sound pressure level generated by the floppy lip reed are almost linear functions of the driving force, static pressure difference across the lip. Observed irregularities in these relations are mainly caused by transitions from one type of beating behavior of the lip against the walls of its housing to another. This beating explains the wide range and the driving force dependence of fundamental frequency, and seems to have a strong effect on the spectral content. The thickness of the lip base is linearly related to the fundamental frequency of lip reed oscillation. PMID- 11757945 TI - Measuring vocal quality with speech synthesis. AB - Much previous research has demonstrated that listeners do not agree well when using traditional rating scales to measure pathological voice quality. Although these findings may indicate that listeners are inherently unable to agree in their perception of such complex auditory stimuli, another explanation implicates the particular measurement method-rating scale judgments-as the culprit. An alternative method of assessing quality-listener-mediated analysis-synthesis-was devised to assess this possibility. In this new approach, listeners explicitly compare synthetic and natural voice samples, and adjust speech synthesizer parameters to create auditory matches to voice stimuli. This method is designed to replace unstable internal standards for qualities like breathiness and roughness with externally presented stimuli, to overcome major hypothetical sources of disagreement in rating scale judgments. In a preliminary test of the reliability of this method, listeners were asked to adjust the signal-to-noise ratio for 12 synthetic pathological voices so that the resulting stimuli matched the natural target voices as well as possible For comparison to the synthesis judgments, listeners also judged the noisiness of the natural stimuli in a separate task using a traditional visual-analog rating scale. For 9 of the 12 voices, agreement among listeners was significantly (and substantially) greater for the synthesis task than for the rating scale task. Response variances for the two tasks did not differ for the remaining three voices. However, a second experiment showed that the synthesis settings that listeners selected for these three voices were within a difference limen, and therefore observed differences were perceptually insignificant. These results indicate that listeners can in fact agree in their perceptual assessments of voice quality, and that analysis synthesis can measure perception reliably. PMID- 11757946 TI - Noisy speech recognition using de-noised multiresolution analysis acoustic features. AB - This paper describes a novel application of multiresolution analysis (MRA) in extracting acoustic features that possess de-noising capability for robust speech recognition. The MRA algorithm is used to construct a mel-scaled wavelet packet filter-bank, from which subband powers are computed as the feature parameters for speech recognition. Wiener filtering is applied to a few selected subbands at some intermediate stages of decomposition. For high-frequency bands, Wiener filters are designed based on a reduced fraction of the estimated noise power, making the consonant features much more prominent and contrastive. The proposed method is evaluated in phone recognition experiments with the TIMIT database. In the presence of stationary white noise at 10-dB SNR, the de-noised MRA features attain a phone recognition rate of 32%. There is a noticeable improvement compared with the accuracy of 29% and 20% attained by the commonly used mel frequency cepstral coefficients (MFCC) with and without cepstral mean normalization (CMN), respectively. The effectiveness of the MRA features is also verified by the fact that they exhibit smaller distortion from clean speech. PMID- 11757947 TI - Cross-spectral methods for processing speech. AB - We present time-frequency methods which are well suited to the analysis of nonstationary multicomponent FM signals, such as speech. These methods are based on group delay, instantaneous frequency, and higher-order phase derivative surfaces computed from the short time Fourier transform (STFT). Unlike more conventional approaches, these methods do not assume a locally stationary approximation of the signal model. We describe the computation of the phase derivatives, the physical interpretation of these derivatives, and a re-mapping algorithm based on these phase derivatives. We show analytically, and by example, the convergence of the re-mapping to the FM representation of the signal. The methods are applied to speech to estimate signal parameters, such as the group delay of a transmission channel and speech formant frequencies. Our goal is to develop a unified method which can accurately estimate speech components in both time and frequency and to apply these methods to the estimation of instantaneous formant frequencies, effective excitation time, vocal tract group delay, and channel group delay. The proposed method has several interesting properties, the most important of which is the ability to simultaneously resolve all FM components of a multicomponent signal, as long as the STFT of the composite signal satisfies a simple separability condition. The method can provide super resolution in both time and frequency in the sense that it can simultaneously provide time and frequency estimates of FM components, which have much better accuracy than the Heisenberg uncertainty of the STFT. Super-resolution provides the capability to accurately "re-map" each component of the STFT surface to the time and frequency of the FM signal component it represents. To attain high resolution and accuracy, the signal must be jointly estimated simultaneously in time and frequency. This is accomplished by estimating two surfaces, which are essentially the derivatives of the STFT phase with respect to time and frequency. To avoid phase ambiguities, the differentiation is performed as a cross-spectral product. PMID- 11757948 TI - Quantitative assessment of vocal development in the zebra finch using self organizing neural networks. AB - To understand the mechanisms of song learning by songbirds it is necessary to have in hand tools for extracting, describing, and quantifying features of the developing vocalizations. The extremely large number of vocalizations produced by juvenile zebra finches and the variability in these vocalizations during the sensorimotor learning period preclude manual scoring methods. Here we describe an approach for classification of vocalizations produced during sensorimotor learning based on self-organizing neural networks. This approach allowed us to construct probability distributions of spectrotemporal features recorded on each day. By training the network with samples obtained across the course of vocal development in individual birds, we observed developmental trajectories of these features. The emergence of stereotypy in sequences of song elements was captured by computing the entropy in the matrices of first- and second-order transition probabilities. Self-organizing maps may assist in classifying large libraries of zebra finch vocalizations and shedding light on mechanisms of vocal development. PMID- 11757949 TI - Limbic encephalitis associated with thymic cancer: a case report. PMID- 11757950 TI - Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation. PMID- 11757951 TI - High prevalence of CSF-containing cysts in superficial hemosiderosis of the central nervous system. PMID- 11757952 TI - John Rankin (1923-1981). PMID- 11757953 TI - Hippocampus selectively supports episodic memory retrieval. PMID- 11757954 TI - Neurological complications of sepsis: critical illness polyneuropathy and myopathy. AB - Sepsis may cause not only failure of parenchymal organs but can also cause damage to peripheral nerves and skeletal muscles. It is now recognized that sepsis mediated disorders of the peripheral nerves and the muscle, called critical illness polyneuropathy (CIP) and critical illness myopathy, are responsible for weakness and muscle atrophy occurring de novo in intensively treated patients. CIP represents an acute axonal neuropathy that develops during treatment of severely ill patients and remits spontaneously, once the critical condition is under control. The course is monophasic and self-limiting. Among the critical illness myopathies, three main types have been identified: a non-necrotizing "cachectic" myopathy (critical illness myopathy in the strict sense), a myopathy with selective loss of myosin filaments ("thick filament myopathy") and an acute necrotizing myopathy of intensive care. Clinical manifestations of both critical illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase. The pathogenesis of these neuromuscular complications of sepsis is not understood in detail but most authors assume that the inflammatory factors that mediate systemic inflammatory response and multiple organ failure are closely involved. In thick filament myopathy and acute necrotizing myopathy, administration of steroids and neuromuscular blocking agents may act as triggers. Specific therapies have not been discovered. Stabilization of the underlying critical condition and elimination of sepsis appear to be of major importance. Steroids and muscle relaxants should be avoided or administered at the lowest dose possible. PMID- 11757955 TI - Variable expression of presenilin 1 is not a major determinant of risk for late onset Alzheimer's disease. AB - We have previously reported a significant association between early-onset Alzheimer's disease (EOAD) and an allele in the promoter of presenilin 1 (PSEN1) significantly decreasing PSEN1 expression in vitro. For late-onset Alzheimer's disease (LOAD), numerous studies have reported inconsistent associations with a PSEN1 intronic polymorphism. We therefore hypothesized that linkage disequilibrium between the intronic PSEN1 polymorphism and the functional promoter polymorphism might explain the conflicting reports in LOAD. We analysed both variations in 356 LOAD patients and 230 controls in a population-based case control study. In addition, we re-analysed all published literature on the PSEN1 intronic polymorphism in a meta-analysis. No significant association was found with the PSEN1 intronic or promoter polymorphism in our case-control sample. In the meta-analysis no major differences between patients and controls were found for the PSEN1 intronic variation. Together, our results do not support a major role for variable expression of PSEN1 in LOAD. PMID- 11757956 TI - DYT1 mutation in primary torsion dystonia in a Serbian population. AB - Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 in the DYT1 gene is responsible for most cases of autosomal dominant early-onset PTD. We analysed the DYT1 mutation in 50 patients from a Serbian population, selected according to the proposed guidelines for diagnostic testing: (a) 38 patients with PTD onset < 26 years, and (b) 12 patients with the disease onset +/- 26 years, but with at least one affected family member with early-onset dystonia. Only three apparently sporadic patients among the 50 individuals tested were positive for the GAG deletion in the DYT1 gene: one with typical, generalized, one with long-lasting, non-progressive segmental, and one with multifocal dystonia. Molecular analysis of relatives in 2 families revealed that the lack of family history was due to reduced penetrance. PMID- 11757957 TI - Chronic bilateral pallidal stimulation and levodopa do not improve gait in the same way in Parkinson's disease: a study using a video motion analysis system. AB - Chronic bilateral internal globus pallidus (GPi) stimulation allows control of levodopa induced dyskinesias (LID) and motor symptoms in severe Parkinson's disease (PD). The effect on gait has not been clearly established. Different results have been reported, mostly consisting of clinical data. The aim of this study was to evaluate, by means of a video motion analysis system (optoelectronic VICON system), the influence of bilateral GPi stimulation on gait in PD. Five patients underwent bilateral GPi stimulation. The preoperative and postoperative (3 months after surgery) clinical gait disturbances (items 29 and 30 of the motor UPDRS), as well as spatial and temporal gait measurements (namely cadence, velocity, stride and step times, single and double limb support times, stride and step lengths) were analysed in off condition (the patient had received no treatment for 12 hours or merely the lowest dose of levodopa allowing him to walk for the gait analysis) and in the on drug condition (after administration of 200 mg of levodopa). The gait analysis was performed with the VICON system. In off condition, there was a statistically significant improvement after surgery for UPDRS III and gait (clinically assessed). In on drug condition, there was a significant improvement for LID whereas UPDRS III and clinical assessment of gait were unchanged. The VICON system also showed that surgery improved gait especially in off condition, but also in on drug condition. Our method allowed exact quantification of the influence of surgery on gait characteristics. As compared with levodopa treatment, the effect of stimulation seems to be different. Indeed, the results suggest only limited effects of pallidal stimulation on the control of stride length and rather point to compensatory additional mechanisms. PMID- 11757958 TI - Prospective assessment of falls in Parkinson's disease. AB - We studied prospectively the epidemiology, clinical impact and prediction of falls in 59 moderately affected patients with Parkinson's disease (PD) (mean UPDRS motor score 31.5; mean age 61 years) and 55 controls (mean age 60 years). At baseline, balance and gait were evaluated extensively. The retropulsion test (response to sudden shoulder pull) was executed first unexpectedly and five more times following prior warning. All persons used standardised scoring forms to document their falls during six months. Thirty patients (50.8 %) and eight controls (14.5%) fell at least once (relative risk [RR] 6.1; 95% confidence interval [CI] 2.5-15.1, p < 0.001). Recurrent (> or = 2) falls occurred in 15 patients (25.4%), but in only two controls (RR 9.0; 95 % CI 2.0-41.7; p=0.001). Recurrent falls were more common among persons taking benzodiazepines (RR 5.0; 95% CI 1.6-15.5; p < 0.01). Sixty-two percent of the falls in patients caused soft tissue injuries, but no fractures occurred. A fear of future falls was common (45.8 % of patients) and was accompanied by restriction of daily activities (44.1 % of patients). Seventy percent of falls reported by patients were'intrinsic' (due to patient-related factors), but falls in controls were mainly (50%) 'extrinsic' (due to environmental factors). None of the baseline posture and gait variables predicted falls adequately. The first 'unexpected' retropulsion test was more often abnormal than all subsequent (predictable) tests. Irrespective of its method of execution, the retropulsion test did not predict falls. A combination of asking for prior falls, disease severity and the Romberg test yielded the best overall diagnostic utility (sensitivity 65 % and specificity 98 %). Recurrent fallers were best predicted by disease severity (RR for Hoehn and Yahr stage 3 was > 100; 95% CI 3.1-585) and asking for prior falls (RR 5.0; 95% CI 1.2-20.9). We conclude that falls are common and disabling, even in relatively early stage PD. Recurrent fallers were best predicted by disease severity and presence of prior falls. Strategies to prevent falls in PD should particularly focus at intrinsic (patient-related) factors, such as minimising the use of benzodiazepines. PMID- 11757959 TI - Surveillance of nosocomial infections in a neurology intensive care unit. AB - To identify overall and site-specific nosocomial infection (NI) rates in patients receiving neurological intensive care therapy, a prospective study was started in 1997 in the ten-bed neurological intensive-care unit (NICU) of the University Hospital of Freiburg, Germany. Case records and microbiology reports were reviewed twice a week, and ward staff were consulted. NI were defined according to the Center for Disease Control and Prevention (CDC) criteria and were categorised by specific infection site. Within 30 months, 505 patients with a total of 4,873 patient days were studied (mean length of stay: 9.6 days). 122 NI were identified in 96 patients (74 patients with one, 18 with two and 4 with three infections. An incidence of 24.2/100 patients and incidence density of 25.0/1,000 patient days of NI in the neurological ICU were documented. Site specific incidence rates and incidence densities were: 1.4 bloodstream infections per 100 patients (1.9 central line-associated BSIs per 1,000 central line-days), 11.7 pneumonias per 100 patients (20.4 ventilator-associated pneumonias per 1,000 ventilator-days), 8.7 urinary tract infections per 100 patients (10.0 urinary catheter-associated urinary track infections (UTIs) per 1,000 urinary catheter days). Additionally, 0.4 cases of meningitis, 0.8 ventriculitis, and 1.2 other infections (catheter-related local infection, diarrhea) were documented per 1,000 patient days. 15% of nosocomial pathogens were A. baumannii (due to a outbreak of an nosocomial pneumonia with A. baumannii), 13% S. aureus, 10% E. coli, 7% CNS,7% Bacteroides spp., 7% Enterobacter spp., 6,5% Klebsiella spp.,5.9% enterococci, 5.9% streptococci, and 4.7% Pseudomonas spp. In eight cases of NI no pathogen could be isolated. In future, data on NI in NICUs should be assessed in greater detail, both to improve the quality of care and serve as a basis for identification and implementation of the most effective measures by which to prevent these infections in patients receiving intensive neurological care. PMID- 11757960 TI - Complex compulsive behaviour in the temporal variant of frontotemporal dementia. AB - OBJECTIVE: As metabolic and structural changes in frontotemporal-subcortical pathways have been reported in patients with obsessive-compulsive disorders, we investigated the correlation between complex compulsive behaviour (CCB) and the distribution of atrophy in a group of 90 patients with frontotemporal dementia (FTD). METHODS: CCB was defined as complex, intentional, and time consuming repetitive behaviour, which was distinguished from simple compulsive behaviour (SCB), such as verbal and motor repetitions and utilisation behaviour. Cortical atrophy on CT and/or MRI was semi-quantitatively assessed in frontal, temporal, parietal and occipital regions, and the pattern of atrophy was compared between patients with and without CCB or SCB. Linear measures were used to establish the presence of caudate atrophy (bicaudate ratio) and ventricular enlargement (bifrontal ratio). RESULTS: CCB was reported in 18 (21%) and SCB in 53 (61%) FTD patients. Frontotemporal atrophy was present in 64 patients (74%), and predominant temporal atrophy in 23 (26%). The pattern of atrophy was asymmetric in 25 patients (29%). Logistic regression analysis showed that temporal lobe atrophy (p < 0.005), as well as asymmetry of atrophy (p < 0.05) were independently associated with CCB, after adjusting for age at onset, gender, duration of symptoms at the time of imaging, severity of atrophy, and bicaudate and bifrontal ratio. No relationship was found between the presence of SCB and the distribution of atrophy, although patients with SCB tended to have more caudate atrophy (p < 0.1). CONCLUSION: Temporal lobe atrophy appears to mediate CCB in patients with FTD, especially if asymmetry of atrophy is present. Future studies with quantitative and volumetric measurements of the cortical and subcortical structures may further clarify the aetiology of CCB in FTD. PMID- 11757961 TI - Vertigo and the enlarged vestibular aqueduct syndrome. AB - An enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear bony malformations in children with sensorineural hearing loss of unknown cause. Most previous reports have focused on hearing loss, but individuals with EVA may also experience paroxysmal vertigo lasting minutes to hours. We report the clinical vestibular features and vestibular function testing of two children and one adult with EVA who had a history of sensorineural hearing loss and presented to our Neurotology Clinic for the evaluation of episodic vertigo. All the patients had an antecedent history of profound bilateral sensorineural hearing loss that had been present since early childhood. The onset of vertigo was delayed into adulthood in one patient. Episodes of vertigo could be triggered by minor head trauma or vigorous physical activity. Despite recurrent episodes of vertigo, vestibular function was normal or moderately impaired compared with the severe auditory deficit. Careful analysis of temporal bone CT demonstrated EVA. Associated enlargement of the membranous endolymphatic sac was evident on brain MRI. While hearing loss is a prominent symptom in patients with EVA, vestibular symptoms may cause referral to a neurologist. Although hearing loss occurs early in childhood, vestibular symptoms can be delayed into adulthood, a finding not previously reported. PMID- 11757962 TI - Colour discrimination impairment is not a reliable early marker of Parkinson's disease. AB - Disturbances of colour visual discrimination have been shown to occur frequently in Parkinson's disease (PD). To verify the potential utility of reduced colour sensitivity as a diagnostic marker of early PD, we examined 14 PD patients, mean age 55.4 years, disease duration 2.3 years, in Hoehn and Yahr stages 1, 1.5, or 2, previously untreated with levodopa. Colour discrimination was measured with the Farnsworth-Munsell 100-hue test in patients who were compared with age matched controls. The examinations were performed under standard conditions in a room illuminated by a daylight lamp Biolux Osram 6500 K. The mean total error score (MTES) and partial error scores (green-yellow and red-green axis) were calculated for every person examined. No significant differences were found between PD patients (MTES 49.1 +/- SD 37) and controls (MTES 37.9 +/- SD 25). Similarly, the mean partial scores were not significantly elevated in PD patients. We found an elevation of error scores exceeding the upper limit of normality (control mean + 2SD) only in three patients. We conclude that colour visual discrimination is not consistently impaired in early stages of PD and does not appear as a reliable early marker of Parkinson's disease. PMID- 11757963 TI - Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. AB - Patients with multiple sclerosis (MS) can benefit from treatment with interferon beta-1b. However, the mechanisms of action of this drug are incompletely understood and effects of interferon beta-lb on axonal injury are not known. A measure of axonal injury can be obtained in vivo using magnetic resonance spectroscopy to quantify the resonance intensity of the neuronal marker, N acetylaspartate (NAA). In a small pilot study, we performed combined magnetic resonance imaging and magnetic resonance spectroscopic imaging on 10 patients with relapsing-remitting MS before and 1 year after starting treatment with subcutaneous interferon beta-lb. Resonance intensities of NAA relative to creatine (Cr) were measured in a large, central brain volume. These measurements were compared with those made in a group of 6 untreated patients selected to have a similar range of scores on the Expanded Disability Status Scale and mean NAA/Cr at baseline. NAA/Cr in the treated group [2.74 (0.16), mean (SD)] showed an increase of 5.5% 12 months after the start of therapy [2.89 (0.24),p = 0.05], while NAA/Cr in the untreated group decreased, but not significantly [2.76 (0.1) at baseline, 2.65 (0.14) at 12 months,p > 0.1]. NAA/Cr had become significantly higher in the treated group at 12 months than in the untreated group (p = 0.03). Our data suggest that, in addition to losing axons, patients with chronic multiple sclerosis suffer from chronic, sublethal axonal injury that is at least partially reversible with interferon beta-lb therapy. PMID- 11757964 TI - Editorial commentary to Narayanan et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. PMID- 11757965 TI - Cerebral vasculitis associated with Reiter's syndrome. PMID- 11757966 TI - Palatal myoclonus appearing 8 years after removal of a cerebellar low-grade astrocytoma. PMID- 11757967 TI - Neurophysiological studies in a patient with heat stroke. PMID- 11757968 TI - Topiramate modulation of R3 nociceptive reflex in multiple sclerosis patients suffering paroxysmal symptoms. PMID- 11757969 TI - Emergence, mechanism, and clinical implications of reduced glycopeptide susceptibility in Staphylococcus aureus. AB - In order to understand the mechanism(s) of the resistance/reduced susceptibility of Staphylococcus aureus to glycopeptide antibiotics, the current data on the modes of action of glycopeptides were reviewed. In addition, the different test systems for detecting vancomycin resistance and the clinical relevance of resistant Staphylococcus aureus were analyzed. Finally, strategies to prevent the nosocomial spread of these bacteria are presented, as are new therapeutic options. PMID- 11757970 TI - Chlamydia pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease: analysis of 250 hospitalizations. AB - Two hundred fifty hospitalizations were included in a serologically based prospective study to assess the role of Chlamydia pneumoniae in episodes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the percentage of COPD patients chronically infected with this pathogen. Chlamydia pneumoniae specific IgG, IgA and IgM antibody titers were determined using a commercial kit with the microimmunofluorescence method. A significantly higher geometric mean titer in the COPD patients compared to the control group was found for IgG (P<0.00001) and IgA (P<0.000001). The serological criterion for chronic Chlamydia pneumoniae infection (IgG > or = 28 concomitant with IgA > or = 64) was positive in 73 (33.3%) COPD patients compared with 7 (7%) controls (P=0.000001). No difference was found in any serological parameter when the study population was divided by severity of COPD. When the serological profiles were compared between the first and second of 31 pairs of hospitalizations, 7 of the 62 (11.3%) hospitalizations showed evidence of acute infection with Chlamydia pneumoniae around one of the episodes of AECOPD. It is concluded that compared with the control group, the COPD patients had a significantly higher prevalence of chronic Chlamydia pneumoniae infection. In the COPD group, there was no correlation between the severity of the disease and the rate of chronic Chlamydia pneumoniae infection. In a substantial percentage of AECOPD cases, there is serological evidence of acute Chlamydia pneumoniae infection around the time of the exacerbation. The clinical and pathophysiologic implications of these findings should be clarified by further studies. PMID- 11757971 TI - Epidemiology of three cases of severe diphtheria in Finnish patients with low antitoxin antibody levels. AB - During the 1990-1998 diphtheria epidemic in the newly independent states of the former Soviet Union, more than 150,000 infections and 5,000 deaths occurred. During this period, more than 10 million trips were made from Finland to Russia or vice versa. This resulted in only 10 cases of diphtheria in Finland. There was no secondary spread to healthcare workers or other close contacts. Three patients had severe respiratory tract diphtheria. All three were middle-aged men who had made a short visit to Russia, during which time they had intimate contact with local women. These findings suggest diphtheria was transmitted mainly by direct saliva contact. All patients with severe diphtheria had a non-protective level of antitoxin antibodies during the first days of the disease. Only the patient whose antibody titre rose rapidly to a protective level (>1 IU/ml) had an uncomplicated recovery. The other two, one of whom died, had myocarditis and severe polyneuropathy. PMID- 11757972 TI - Cryptococcus neoformans infection in a cohort of Italian AIDS patients: natural history, early prognostic parameters, and autopsy findings. AB - This observational cohort study of 4,160 AIDS patients hospitalised in a single institution in northern Italy between January 1985 and December 1999 was carried out in order to assess the natural history of cryptococcosis, the epidemiological trend of this opportunistic infection, the risk factors predictive of death at 10 weeks, the response to therapy, and autopsy findings. Cryptococcosis was diagnosed in 177 (4.2%) patients and was the AIDS-defining disease in 2.8% of cases. Its prevalence decreased significantly over time (from 6.4% in the period 1985-1989 to 5.7% in 1990-1993, 3.1% in 1994-1996, and 1.9% in 1997-1999, P <0.0001). Although neurologic disease was the most frequent clinical picture, a significant proportion of the patients (24.2%) presented with extraneural cryptococcosis. In a Cox multivariate analysis, high titres of cerebrospinal fluid antigen (>5000) and drug addiction were predictive of death at 10 weeks. A complete clinical and mycological response was achieved in 60.8% of the treated patients, with the highest response rate being observed in those treated with amphotericin plus flucytosine (66.6%). Cryptococcosis relapsed in 12.8% of patients on secondary prophylaxis. Autopsy findings demonstrated that cryptococcosis is a disseminated disease, but long-term antifungal treatment may be able to eradicate it in a subgroup of patients. PMID- 11757973 TI - Evaluation of five commercial Sabouraud gentamicin-chloramphenicol agar media. AB - The diagnosis of fungal infections relies on the isolation of the causative agent by culture of clinical specimens. Among the different culture media, Sabouraud glucose agar remains the most widely used. The use of commercial culture media is highly recommended as good laboratory practice in clinical microbiology. Therefore, the comparative performance of five different Sabouraud gentamicin chloramphenicol agar media, available commercially as plates, was investigated. A total of 124 strains encompassing 45 yeasts and 79 filamentous fungi were cultured. Colonies of the dermatophytes (28 strains) and some related keratinophilic fungi (6 strains) were of overall similar appearance or size on all five media. Conversely, all the Aspergillus strains tested (n=17) as well as a few other strains of Hyphomycetes (n=5/18) exhibited important differences in the colour of the colonies. Furthermore, growth of the members of Mucorace ae was also affected, with great differences in the diameter of the colonies observed. In addition, quantitative cultures of the yeasts revealed marked variations in the number of the colonies, or even no growth, for two Candida species, Cryptococcus species, and Trichosporon cutaneum. In conclusion, the only formulation that gave good results with all fungal types tested was the one from Becton Dickinson (France). PMID- 11757974 TI - Multicenter study of a commercial, automated polymerase chain reaction system for the rapid detection of Mycobacterium tuberculosis in respiratory specimens in routine clinical practice. AB - A cooperative study was conducted among six laboratories to compare the performance of the Cobas Amplicor (CA) polymerase chain reaction (PCR) system (Roche Molecular Systems, USA) for the detection of Mycobacterium tuberculosis with that of microscopy and culture in routine clinical laboratory diagnosis. A total of 5,221 decontaminated respiratory specimens were tested. The use of an internal control allowed detection of PCR inhibition in 144 (2.8%) specimens. Only two culture-positive samples were CA PCR inhibitory and therefore could not be detected by PCR testing. Of the 333 culture-positive specimens, 278 (83.5%) were positive by the CA PCR. Of the 4,744 culture-negative specimens, 52 (1.1%) were positive by the CA PCR. After analysis of discrepancies, 40 of the 52 culture-negative, CA PCR-positive specimens were classified as true positive. Thus, the overall sensitivities of culture, CA PCR and microscopy were 89.3%, 85.2% and 55.5%, respectively. The overall specificity of the CA PCR was 99.7%. Five of the six centers found similar performances for the CA PCR, with sensitivities ranging from 85.7 to 90.9%. The CA PCR was more sensitive for smear positive samples, exhibiting overall sensitivities of 96.1% and 71.7% for smear positive and smear-negative specimens, respectively. These results indicate that the Cobas Amplicor system enables microbiology laboratories with reasonable previous experience in molecular biology testing to perform PCR and to detect Mycobacterium tuberculosis in more than 70% of specimens obtained from infected patients. PMID- 11757975 TI - Cat scratch disease due to Bartonella henselae infection mimicking parotid malignancy. AB - An unusual Bartonella henselae infection presenting clinically as a putative parotid cancer was diagnosed based on serological tests, histomorphology and amplification of a 16S-rDNA sequence of Bartonella henselae. The patient improved greatly upon antibiotic treatment and did not require surgery. Although uncommon, infection with Bartonella spp., particularly Bartonella henselae, should be included in the differential diagnosis of parotid tumors. PMID- 11757976 TI - Clinical and genetic analysis of Staphylococcus aureus nasal colonisation and exit-site infection in patients undergoing peritoneal dialysis. AB - Few data exist regarding the clonal identity of Staphylococcus aureus (SA) that colonises the nostrils and causes exit-site infections in peritoneal dialysis patients. Nasal and exit-site swabs were taken monthly from 41 patients undergoing peritoneal dialysis, and a genetic analysis of SA isolates was performed by pulsed-field-gel electrophoresis. When SA was identified at the exit site, the clonal identity of nasal and exit-site isolates was demonstrated. In 50% of the SA carriers, nasal isolates were genetically constant over time; in the other 50% a change of colonising SA strains was observed. The risk of exit site infection was identical in both groups. PMID- 11757977 TI - Evaluation of the Bartels Legionella Urinary Antigen enzyme immunoassay. AB - The Bartels Legionella Urinary Antigen enzyme immunoassay (Intracel, USA) is intended for the presumptive diagnosis of past or current Legionnaires' disease by qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine. This test was evaluated using single urine samples collected from 349 patients with lower respiratory tract infection of known aetiology. Specificity was estimated as 100% (181 samples, 95% CI: 98%-100%); sensitivity for Legionella pneumophila serogroup 1 was 98.8% (167 samples, 95% CI: 95.7%-99.9%). Assessing assay results using a Visual Interpretation Card provided by the manufacturer in place of a photometer gave rise to one false-positive result among the 78 control samples examined. Providing the endpoint of this assay is determined photometrically, the Bartels Legionella Urinary Antigen enzyme immunoassay appears to be a highly specific and sensitive kit for the diagnosis of infection caused by Legionella pneumophila serogroup 1. PMID- 11757978 TI - New immunochromatographic method for rapid detection of rotaviruses in stool samples compared with standard enzyme immunoassay and latex agglutination techniques. AB - Three different commercial immunologic tests for rapid detection of group A rotavirus (an immunochromatographic method, latex agglutination, and enzyme immunoassay) were used to evaluate 228 faecal specimens obtained from Spanish children with acute gastroenteritis. After resolution of 30 (13.2%) discordant results by reverse transcription-polymerase chain reaction for rotavirus, the statistical values of the enzyme immunoassay, latex agglutination, and immunochromatographic method were respectively 96%, 68%, and 99% for sensitivity; 99%, 99%, and 96% for specificity; 98%, 96%, and 92% for positive predictive value; and 98%, 88%, and 99% for negative predictive value. The immunochromatographic technique showed high sensitivity and specificity and was rapid and easy to perform in the routine clinical laboratory. PMID- 11757979 TI - Diagnosis of disseminated zygomycosis using a polymerase chain reaction assay. AB - Invasive pulmonary zygomycosis is an uncommon opportunistic infection in patients with haematological malignancies. Clinical manifestations are in distinguishable from the more frequent invasive aspergillosis. Standard diagnostic methods like culture and microscopy from respiratory secretions have a low diagnostic sensitivity. A case in which proven invasive pulmonary zygomycosis was confirmed using a panfungal polymerase chain reaction assay in blood is presented. Since zygomycosis requires more aggressive treatment than aspergillosis (high-dose amphotericin B and surgical intervention), the polymerase chain reaction assay may improve the outcome of these often fatal infections by guiding the therapeutic approach through an early, non-invasive diagnosis. PMID- 11757980 TI - Evaluation of commercial DNA and rRNA amplification assays for assessment of treatment outcome in pulmonary tuberculosis patients. AB - To evaluate the clinical utility of the DNA and RNA amplification assays in monitoring the efficacy of tuberculosis treatment, 416 sputum specimens collected from 15 smear-positive tuberculosis patients during and after treatment were tested for the presence of Mycobacterium tuberculosis by microscopy, culture, polymerase chain reaction (Cobas Amplicor Mycobacterium Tuberculosis Test; Roche, Switzerland) and AMTDT 2 (Amplified Mycobacterium Tuberculosis Direct Test; Gen Probe, USA). All patients were cured, and no relapses were found. Results of both amplification assays re mained positive longer than results of either smear or culture. Four of 15 patients were positive by polymerase chain reaction and/or AMTDT 2 at the completion of treatment. Subsequent sputum specimens from these patients converted to negative within 2.5-12 months. The present data do not support the routine use of qualitative amplification assays for monitoring the treatment response of smear-positive tuberculosis patients. PMID- 11757981 TI - Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain. PMID- 11757982 TI - A case of oral localized histoplasmosis in an immunocompetent patient. PMID- 11757983 TI - A case of Rothia dentocariosa endophthalmitis. PMID- 11757984 TI - Manuka honey used to heal a recalcitrant surgical wound. PMID- 11757985 TI - Intermediate susceptibility to ciprofloxacin in Salmonella typhi strains in India. PMID- 11757986 TI - Detection of a new 16S-23S rRNA spacer sequence variant (type 7) of Tropheryma whippelii in a patient with prosthetic aortic valve endocarditis. PMID- 11757987 TI - Changes in plasma antiproteases in paraquat poisoned rats using micro two dimensional electrophoretic analysis. AB - Rats were subjected to subacute paraquat (PQ) exposure (7 mg/kg sc daily for 6-9 administrations). They were divided into a group that died from subacute toxicity, a group that recovered from the subacute toxicity and progressed to pulmonary fibrosis, and a group that showed no effects from the PQ. The rats with subacute fatal toxicity had a remarkable increase in a2M-1. Those which progressed to pulmonary fibrosis had remarkable decreases in a2M-2, a2M-3, and a2M-4 and a1AT. The rats that showed no effects from the PQ had relative increases in all molecular species of a2M. Increases in major a2M molecular species, a2M-1 and a2M-4, and a minor molecular species, a2M-3, were characteristically observed. PMID- 11757988 TI - Acute and chronic toxicity of fessoukh, the resinous gum of Ferula communis L, compared to warfarin. AB - The acute toxicity of the fessoukh extract (FE) was studied in rats and mice. In single oral dose administration mode, FE has moderate toxicity; the LD50s were 1650 mg/kg bw in rats and 2000 mg/kg bw in mice. In albino rats, with baits containing 0.01 to 10% FE, 0.01% produced 100% mortality in 15 d; with 0.1%, all rats died in 9 d. Baits containing 0.1% were toxic, more consumed, required less product and did not cause apprehension in the rats. A trial conducted with wild rats (Rattus norvegicus) using 0.1% FE baits demonstrated fessoukh's rodenticide effects. PMID- 11757989 TI - Effects of dietary formalin on the health and testicular pathology of male Japanese quails (Coturnix coturnix Japonica). AB - Male Japanese quail (n = 75) at 35 d of age were fed 20.0, 10.0, 5.0, 2.5 or 0 ml formalin (37% formaldehyde)/kg of their daily ration for 8 w. Quail fed 20.0 or 10.0 ml formalin/kg feed showed depression, decreased responsiveness, feed consumption, and body weights, and had vacuolation in the germinal epithelial layer of their seminiferous tubules. Formalin feeding at up to 5 ml/kg was associated with decreased weight of testes, and up to 2.5 ml/kg feed resulted in smaller diameter seminiferous tubules. PMID- 11757990 TI - Toxicity of dietary Heliotropium dolosum seed to broiler chickens. AB - Five groups of 20 female broiler chicks were fed different levels of dehulled Heliotropium dolosum seed (w/w%; 0.0, 1.0, 3.0, 5.0 or 10.0%) from 10 to 52 d of age. In all doses the seed caused decreases in daily feed intake, weight gain, and feed efficiency, and biochemical findings, severity of pathologic changes, and mortality rate increased in a dose-dependent manner. Acute toxicity was observed in livers of chicks fed 10% seed. Other test groups had chronic changes. Livers had massive to submassive necrosis, hepatic megalocytosis, bile duct proliferation, fatty change, and periportal fibrosis. Biochemical evaluations revealed hypoalbuminemia, hypoprotienemia and increased ALP activity and billuribin. The seed of Heliotropium dolosum produced biochemical and specific pathologic changes in broiler chicks, as well as decreased food intake and feed efficiency. Higher seed levels induced more pronounced changes. PMID- 11757991 TI - Atypical presentation of risperidone toxicity. AB - A new class of antipsychotic medication, the "atypical antipsychotics" are gaining popularity. We report 2 cases of toxicity associated with 1 of these new antipsychotics, risperidone. Both patients presented with fatigue, orthostasis, dry mucous membranes, and the unusual finding of miosis. The pathophysiology and clinical presentation of overdose with this agent are discussed. PMID- 11757992 TI - Relative safety of mirtazapine overdose. AB - A 43-y-o male with a history of AIDS, atrial fibrillation, and alcohol abuse presented to the emergency department 2 h after ingestion of 25 tablets of 15 mg mirtazapine (total 375 mg) with ethanol in a suicide attempt (no other coingestion). Vital signs were normal except for a mild tachycardia (rate 112). Physical examination was unremarkable except for lethargy. Fifty grams of activated charcoal with sorbitol was given. Electrocardiogram showed sinus tachycardia, left ventricular hypertrophy, and non-specific ST-segment changes. Serum mirtazapine on admission was 530 ng/mL (therapeutic level 20-50 ng/mL). Overnight monitoring revealed no tachyarrythmias, and discharge occurred after psychiatric evaluation. It appears that ingestions of mirtazapine approximately 10-fold of therapeutic exhibit minimal acute toxicity. From this and other cases in the literature exhibiting a 10-fold overdose, we conclude that isolated mirtazapine ingestions of this magnitude require no acute intervention other than short term (about 6 h) observation. PMID- 11757993 TI - Pancytopenia, hyperglycemia, shock, coma, rhabdomyolysis, and pancreatitis associated with acetaminophen poisoning. AB - It is well recognized that acetaminophen overdose can cause severe hepatic injury. However, extra-hepatic manifestations may also develop following inappropriate use or ingestion of large amounts of acetaminophen. We present a 44 y-o female who manifested coma, metabolic acidosis, shock, hypothermia, hyperglycemia, rhabdomyolysis, hepatotoxicity, and renal insufficiency after suicidal ingestion of an unknown amount of acetaminophen. Although her consciousness and hemodynamic status gradually improved after treatment with N acetylcysteine and other supportive measures, she was found to have pancytopenia, pancreatitis and hepatorenal failure during the hospitalization and eventually died 18 d post-admission. Review of relevant literature reports and the clinical findings in our patient suggests that direct toxic effects mediated by acetaminophen or its metabolites were most likely responsible for most of the observed clinical features. PMID- 11757994 TI - Ethanol toxicosis from the ingestion of rotten apples by a dog. AB - We report a case of ethanol intoxication from massive rotten apples ingestion. The dog exhibited vomiting, ataxia, tremors, dehydratation, and died 48 h later with an alcoholemia of 300 mg/dL. PMID- 11757995 TI - 4-aminopyridine poisoning of crows in the Chicago area. AB - Poisoning of crows with the avicide 4-aminopyridine is reported. Seven crows had frequent vocalization and nervous signs; 6 died. Postmortem examination of 4 found evidence of trauma and corn-based bait present in the gastrointestinal tract. The bait contained 4-aminopyridine, a rapidly fatal nervous system toxin. When utilized by pest control professionals using manufacturer's recommendations, 4-aminopyridine has little risk of direct or relay toxicosis to non-target species. Treatment of exposed individuals involves symptomatic care and control of seizures. PMID- 11757996 TI - Toxicology of various anticoagulant rodenticides in animals. AB - Anticoagulant rodenticides act by interrupting cellular recycling of vitamin K and inducing a secondary coagulopathy. Their sensitivity to different animal species is reviewed. PMID- 11757997 TI - Beta-adrenergic antagonist exposures in children. AB - Since limited toxicological data exists for beta-adrenergic antagonist (BA) exposures in children, a survey to describe triage practices by regional poison centers nationwide and to characterize clinical manifestations of unintentional pediatric BA exposures was sent to 49 poison centers. A 7-y retrospective review of acute BA exposures in children aged < 7years from 1 regional poison center was also undertaken. Thirty-three centers (67%) responded: 19/33 (58%) had no established BA triage guideline for young children. The 14/33 remaining centers (42%) most often referred these children to a hospital if any BA was ingested. In the 1-center review, metoprolol (28%) and atenolol (27%) exposures were most common, but = 1 tablet of BA was involved in 83% of the exposures. Symptoms occurred in 8 children; 2/378 had lethargy and 6/378 had bradycardia and/or hypotension. Immediate-release preparations were ingested by 7/8 symptomatic patients (median time to onset of symptoms = 3.0 h, range 45 min to 3.5 h). Of 280 children with definitive follow-up, 272 had no clinical effects, 4 had minor effects, and 4 had moderate effects. Regional poison centers commonly refer children exposed to any amount of BA to the hospital. The majority of BA exposures involved a small amount and significant clinical effects were rare. The range of toxicity for BA in children needs to be established. PMID- 11757998 TI - Toxidromes associated with the most common plant ingestions. AB - Toxicology and botanical references describe a myriad of symptoms associated with the ingestion of plants. The symptoms are based largely on a limited number of case and anecdotal reports or the personal experience of authors: there is little consistency between and among the references. This project compiled a list of symptoms associated with common plant ingestions. Exposure data from the American Association of Poison Control Centers were queried to identify the 20 most commonly ingested plants and the most frequent symptoms associated with those ingestions; 768,284 plant exposures were analyzed and symptoms occurred in 53,081 patients. The 20 most frequently ingested plants accounted for 54.2% of the reported symptoms. Most plant ingestions were not associated with the development of symptoms. PMID- 11757999 TI - Oviductural carcinoma in B6C3F1 female mice exosed to 0.5 ppm ozone. AB - The toxicity and carcinogenecity of ozone was evaluated in B6C3F1 mice exposed to 0.5 ppm ozone via inhalation for 12 w, during which no ozone-related deaths occurred. Decreases in mean body weights of both genders exposed to ozone were sporadically seen, and mean absolute and relative weights of several organs from male and female groups receiving ozone were lower than those of respective air control groups. No ozone-related increased neoplasm incidences were observed in most organs, including the lung; however, oviductural carcinomas were seen in the ozone-exposed females. Although ozone does not induce lung cancer under our experimental condition, it induces oviductural carcinomas in B6C3F1 mice. PMID- 11758000 TI - Jellyfish stings. PMID- 11758001 TI - Misdiagnosis of myoclonus in antidepressant induced serotonin excess. PMID- 11758002 TI - "Avoid inconsequentials but attend to details-duh?". PMID- 11758003 TI - Integrative physiology of basal water permeability in the distal nephron: implications for the syndrome of inappropriate secretion of antidiuretic hormone. AB - Patients who drink more electrolyte-free water than they can excrete may develop hyponatremia. A subgroup of hyponatremic patients has a reduced excretion of electrolyte-free water and a low rate of excretion of solutes even though vasopressin is not detected in their plasma. Basal water permeability in the distal nephron, by permitting a limited volume of electrolyte-free water to be reabsorbed, offers a way to help explain these findings. Basal water permeability will also be considered from the perspective of integrative physiology in evolutionary and developmental biology settings. Its possible clinical importance will be explored in patients with chronic hyponatremia who have a low distal volume delivery. These patients may develop osmotic demyelination if a large solute load leads to a very rapid excretion of electrolyte-free water. PMID- 11758004 TI - Chlamydia pneumoniae infection and accelerated development of coronary artery disease in patients with chronic renal failure. AB - AIMS: This study examined the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and the accelerated development of coronary artery disease (CAD) in patients with chronic renal failure (CRF). METHODS: Two-hundred and fourteen patients undergoing coronary angiography, including 67 controls and 147 patients with CAD (97 without CRF and 50 with CRF), were enrolled in this study. Anti-C. pneumoniae specific IgG and IgA antibodies were measured using an enzyme linked immunosorbent assay (ELISA). RESULTS: Coronary artery disease (expressed as CAD score) was more severe in patients with than without CRF (14.9 +/- 6.0 vs. 11.3 +/- 6.0, p < 0.01). Seropositive rates of IgG and IgA antibodies against C. pneumoniae were higher in all CAD patients than in the controls (76.2% vs. 44.8%, p < 0.001 for IgG; 59.9% vs. 40.3%, p < 0.01 for IgA). In both CAD subgroups, IgG seropositive rates were similarly elevated (82.0% and 73.2% vs. 44.8% for control, p < 0.001, respectively), whereas those of IgA were significantly elevated only in CAD with CRF (68.0% vs. 55.7% for control, p < 0.01). The mean antibody index of IgG was elevated in all CAD patients compared with the controls (1.9 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.0001), but that of IgA was not (1.5 +/- 1.0 vs. 1.2 +/- 0.9). Levels of IgG were elevated in all patients with CAD compared with the control (2.4 +/- 1.1 and 1.8 +/- 1.0 vs. 1.3 +/- 0.9, p < 0.001 and p < 0.001, respectively), whereas those of IgA were elevated only in CAD with CRF (1.8 +/- 1.1 vs. 1.2 +/- 0.9, p < 0.05). Stepwise logistic regression analysis revealed that the elevated IgG antibody index was an independent risk factor for CAD regardless of CRF (odds ratios 1.9, 1.8, and 2.3), whereas the IgA index was a risk factor only in CAD with CRF (odds ratio 1.7). CONCLUSIONS: Chlamydia pneumoniae infection may be related to the accelerated CAD in patients with CRF, which was specifically suggested by an elevated IgA level. In other words, the prevalence of active C. pneumoniae infection is higher in patients with CAD and CRF than that in those with CAD without CRF. PMID- 11758005 TI - Persistently increased bone turnover and low bone density in long-term survivors to kidney transplantation. AB - AIMS: There are few data on the long-term outcome of bone health in renal transplant recipients. We wanted to evaluate the prevalence of osteoporosis and related clinical fractures in long-term survivals to kidney transplantation. METHODS: We carried out a cross-sectional study of 80 males and 44 females, aged 45 +/- 1 years, who had undergone kidney transplantation (KTx) 55.6 +/- 4.6 months earlier. Patients were treated according to standard immunosuppressive protocols. RESULTS: High parathyroid hormone levels were observed in 55 out of the 124 patients (44.6%) and the prevalence of secondary hyperparathyroidism (SHPT) remained similar even when subjects were grouped according to the time elapsed since transplant. The Z scores for bone alkaline phosphatase, osteocalcin, urinary N telopeptide and galactosyl-hydroxylysine were increased as compared to normal controls, both in males and females (p < 0.05). Bone formation markers normalized, while bone resorption markers remained elevated in these patients even ten years after transplant. Vertebral and femoral osteoporosis were present in 37% and 56% of the patients, respectively, and no tendency toward a recovery in bone mass was seen even in those patients who had survived the longest time since KTx. Clinical fracture rate was 0.006 and 0.031 patient years, before and after KTx, respectively. The number of fractures was lower in patients taking lower mean daily doses of corticosteroids (p < 0.025). PTH levels positively correlated with bone alkaline phosphatase, osteocalcin and N telopeptide. CONCLUSION: In conclusion, bone density is decreased and bone turnover increased even many years after KTx, with persistent SHPT and corticosteroid use being the main pathogenetic factors. PMID- 11758006 TI - Effects of posture and positive airway pressure on plasma atrial natriuretic peptide and renal urodilatin excretion. AB - AIMS: To determine whether a coupling of plasma atrial natriuretic peptide (ANP) and renal excretion of urodilatin (U(URO)V)--recently observed during supraphysiological concentrations of ANP--may also be detected during moderate changes in ANP levels, i.e. if ANP is increased by supine positioning and decreased by applying continuous positive airway pressure (CPAP). MATERIAL AND METHODS: We investigated 10 healthy male volunteers, orally hydrated with 200 ml water/h, in a randomized crossover study for periods of 1 hour following 2 protocols. Protocol 1: sitting and supine position. Protocol 2: sitting with and without a CPAP of 8 cm H2O. RESULTS: ANP increased ongoing from the sitting to the supine position (SIT-1: 13.2 +/- 4.7; SUP: 27.9 +/- 21.9 pg x ml(-1); p < 0.01) during protocol 1 and decreased after the onset of CPAP in seated subjects (SIT-2: 16.9 +/- 7.9; SIT-CPAP: 13.9 +/- 6.5 pg x ml(-1); p < 0.05) during protocol 2. U(URO)V decreased slightly, but not significantly, during protocol I (SIT-1: 63.9 +/- 21.7; SUP: 49.9 +/- 13.2 fmol x min(-1)) and remained unchanged after institution of CPAP in the sitting position (SIT-2: 68.5 +/- 25.2; SIT CPAP: 68.5 +/- 50.2 fmol x min(-1)). Correlation analysis revealed no relationship between plasma ANP and U(URO)V. CONCLUSIONS: Moderate variations in the levels of ANP in water-loaded volunteers do not induce parallel changes in the urinary excretion of urodilatin. PMID- 11758007 TI - Association between circulating leptin and soluble receptors for tumor necrosis factor-alpha in hemodialysis patients. AB - BACKGROUND: The expression of leptin, an adipocyte-derived protein, is regulated by tumor necrosis factor-alpha (TNF-alpha). Since circulating leptin levels adjusted for body fat mass are reported to be increased in dialysis patients, we examined if the TNF-alpha system may influence blood leptin levels in hemodialysis (HD) patients. PATIENTS AND METHODS: Sixty-three stable HD patients who had no signs of infection, collagen disease or malignancy were enrolled in the study (age: 63 +/- 1 years, duration of HD: 14 +/- 1 years, male/female = 34/29). We measured serum leptin, TNF-alpha, soluble receptors for TNF-alpha (sTNFR p55, p80) and interleukin-6 (IL-6) concentrations with ELISA kits. Body fat mass was determined using DEXA. To evaluate the potential association between serum leptin and the TNF-alpha system, we compared serum leptin and sTNFR levels, which has been validated as a sensitive marker of activation of the TNF-alpha system. RESULTS: Serum leptin levels were significantly higher in female patients compared to male patients (14.07 +/- 3.60 vs. 4.26 +/- 0.85 ng/ml, p < 0.005). A strong correlation was found between serum leptin levels and estimated body fat mass both in males (r = 0.742, p < 0.0001) and females (r = 0.769, p < 0.001), respectively. Serum TNF-alpha, sTNFR p55, p80 and IL-6 levels were significantly increased in HD patients compared to normal subjects. However, no association was found between serum leptin and serum TNF-alpha, sTNFR p55, p80 and IL-6 levels. Serum leptin levels were significantly correlated with the atherosclerotic index both in men (r = 0.382, p = 0.027) and women (r = 0.281, p = 0.041). In contrast, there was no relationship between circulating leptin values and serum albumin, transferrin, creatinine levels, or normalized protein catabolic rate in each sex. CONCLUSION: These findings suggested that serum leptin is independent of the TNF alpha system, and is mainly correlated with body fat volume in HD patients. Elevation of circulating leptin may be associated with the disturbance of the serum lipid profile rather than malnutrition in patients receiving long-term HD. PMID- 11758008 TI - Alpha-interferon therapy increases serum beta2-microglobulin levels in hemodialysis patients. AB - BACKGROUND/AIMS: Beta2-microglobulin is the main component of dialysis-associated amyloid. Interferons (IFNs) have the ability to induce an increase in the formation and release of this protein. The aim of this study was to evaluate serum beta2-microglobulin levels in 11 hemodialysis patients with chronic hepatitis C treated with IFNalpha. METHODS: Eleven hemodialysis patients with chronic hepatitis C that received IFNalpha treatment were included in this study. No patient had residual renal function. High-flux membranes were used in 5 patients, and low-flux membranes in the remaining 6 patients. Beta2-microglobulin was analyzed at baseline, during IFNalpha treatment and after IFNalpha was stopped. RESULTS: Serum beta2-microglobulin concentration rose in all patients during the IFNalpha therapy. Compared with baseline values (43 mg/l, range 22-59) the median beta2-microglobulin levels increased significantly at one month (65 mg/l, range 37-142, p = 0.008) and at 12 months (59 mg/l, range 42-137, p = 0.003) after the beginning of IFN therapy. One month after IFNalpha was discontinued, beta2-microglobulin decreased significantly (median 48, range 34-75 mg/l, p = 0.05) in comparison with that obtained at the end of the therapy. The increase observed during IFN therapy was lower in patients treated with high-flux membranes than in those with low-flux membranes, although it was not statistically different. CONCLUSION: Our results show that IFNalpha therapy increases serum beta2-microglobulin levels in hemodialysis patients. Further studies are needed to clarify whether the use of high-flux membranes should be recommended in hemodialysis patients requiring IFN treatment. PMID- 11758009 TI - Pharmacokinetic study of human natural beta-interferon in patients with end-stage renal failure. AB - AIMS: Although human natural beta-interferon (beta-IFN) is currently used in the treatment of a number diseases, there have been no published studies of the pharmacokinetics and pharmacodynamics of beta-IFN in patients with end-stage renal failure. MATERIALS: Five maintenance hemodialysis patients with chronic hepatitis C (4 men and 1 woman) were enrolled in this study. METHODS: For the pharmacokinetic study, blood samples were obtained from a forearm vein at intervals, before infusion and 0, 3, 5, 10, 20, 30, and 40 minutes after a 15 minute intravenous infusion of human natural beta-IFN (Feron, Toray Industries, Inc., Tokyo) at a dose of 600 MIU. RESULTS: Intravenous beta-IFN was administrated safely to all five patients. The plasma half-life of beta-IFN was found to be 6.91 +/- 2.80 (mean +/- SD) minutes. The initial volume of distribution was found to be 0.49 +/- 0.02 l/kg. CONCLUSION: A 15-minute intravenous infusion of human natural beta-IFN was safely administered to the hemodialysis patients. This pharmacokinetic study showed that it is not necessary to reduce the dosage in patients with end-stage renal failure. PMID- 11758011 TI - Acute renal failure caused by Klebsiella pneumoniae pyelonephritis. AB - We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli. PMID- 11758010 TI - Depression, anxiety and adjustment in renal replacement therapy: a quality of life assessment. AB - OBJECTIVES: To measure the quality of life (QOL) of patients on RRT with regard to depression, anxiety, and adjustment to illness. MATERIAL: The study was conducted between 1996 and 1998 at a teaching hospital in Porto Alegre, Brazil. The study population included 125 patients (transplant n = 64, hemodialysis n = 42 and continuous ambulatory peritoneal dialysis [CAPD] n = 19). METHODS: The Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), and the Psychosocial Adjustment to Illness Scale (PAIS) were used for patient assessment. Results were analyzed using the Kruskall-Wallis, Mann-Whitney and ANOVA tests. RESULTS: Depression scores were higher for hemodialysis patients compared with transplant patients (H = 15.22; p < 0.005). CAPD patients had intermediate scores (no statistical difference). As far as anxiety was concerned, no statistical difference was observed when the groups were compared. In terms of adjustment to illness, hemodialysis patients were significantly less well adjusted than transplant patients (H = 23.34; p < 0.001). Patients on CAPD had intermediate scores, with no significant difference compared with the other two groups. CONCLUSION: The overall quality of life of transplant patients is higher than that of hemodialysis patients. PMID- 11758012 TI - Membranous nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis: a report of 2 cases. PMID- 11758013 TI - Crystal nephropathy: a variant form of myeloma kidney--a case report and review of the literature. AB - Cast nephropathy is the most common form of myeloma kidney, and also one of the major determinants of a patient's prognosis. We experienced a case of multiple myeloma with acute renal failure that was associated with massive crystal deposition in kidney and bone marrow. Large crystal formation in myeloma kidney is a rare pathological finding in renal biopsies. In the literature, most of the cases with multiple myeloma with extracellular crystal deposition often have a rapidly progressive course with a poor prognosis. Ball et al. [1993] suggested that this type of extracellular crystal deposition be designated as "crystalglobulinemia syndrome". The characteristics of the clinical and histopathological features, rapid progression and poor outcome, and crystal formation in the tubules found in the present case and in those previously reported, support the proposal of a new concept of "crystal nephropathy". PMID- 11758014 TI - Giant cell arteritis and renal amyloidosis: report of a case. AB - Polymyalgia rheumatica and giant cell arteritis are rarely associated with renal diseases such as amyloidosis. Here is a case of a 72-year-old man, who developed some renal failure and a nephrotic syndrome while presenting clinical symptoms of giant cell arteritis. Percutaneous renal biopsy showed secondary amyloidosis, and temporal artery biopsy revealed some lesions which suggested temporal arteritis. In spite of aggressive steroid treatment, chlorambucil, and colchicine, the patient's renal function continued to deteriorate and the patient is now being given hemodyalisis. PMID- 11758015 TI - Progressive demyelinating neuropathy after initiation of continuous ambulatory peritoneal dialysis--report of two cases. AB - We report on two patients who developed rapidly progressive demyelinating neuropathy within 6 to 10 weeks after the initiation of continuous ambulatory peritoneal dialysis. The neuropathy in one patient resolved after kidney transplantation while that of the other patient improved with immunosuppressive therapy. The close temporal relationship between the initiation of peritoneal dialysis and the onset of neuropathy suggests that these two events may be causally related. PMID- 11758016 TI - Renal involvement after lung transplantation for sarcoidosis. PMID- 11758017 TI - RPA position on the frequency of hemodialysis in outpatients. PMID- 11758018 TI - Prenatal informed consent for sonogram: the time for first-trimester nuchal translucency has come. PMID- 11758019 TI - The genetic sonogram in screening for Down syndrome. PMID- 11758020 TI - Prenatal diagnosis of cleft lip: what the sonologist needs to tell the surgeon. PMID- 11758021 TI - Prenatal ultrasonography and the diagnosis of fetal cleft lip. AB - OBJECTIVE: To determine the efficacy of obstetric ultrasonography in the detection of fetal cleft lip. METHODS: The study population included all women who had a fetal anatomic survey with adequate visualization of the face and who gave birth at Brigham and Women's Hospital between January 1, 1990, and January 31, 2000. All neonates born with cleft lip were identified from the Brigham and Women's Active Malformation Surveillance Program. Confirmation of the anatomic defect was obtained from the pediatric record or from the pathologic report if the pregnancy was terminated or ended in miscarriage. Cases of isolated cleft palate were excluded. An ultrasonography database was used to identify all cases of cleft lip diagnosed before delivery. Maternal information regarding the pregnancy was abstracted from the medical record. Statistical significance was determined using the chi2 statistic for categorical variables and the t test for continuous variables. RESULTS: A total of 56 confirmed cases of cleft lip were identified in the study population. Overall, 73% of the cases (41 of 56) were identified antenatally. Additional fetal anomalies were present in 54% of the cases (30 of 56). A comparison between those cases that were detected and those in which the diagnosis was missed showed that there was a significantly lower detection rate if the ultrasonography was performed before 20 weeks (12 [57%] of 21 versus 29 [83%] of 35; P = .035). There was no difference between the 2 groups in terms of maternal age or weight. Maternal parity, prior maternal abdominal surgery, the presence of a multiple gestation, or coexisting fetal anomalies did not significantly affect the detection rate. There was no difference in detection rate in the first half of the study period (1990-1995; 23 [72%] of 32) compared with the second half (1996-2000; 18 [76%] of 24; P = .79). CONCLUSIONS: In this cohort of women, the rate of detection of fetal cleft lip was significantly lower when the anatomic survey was performed before 20 weeks' gestation. This difference could not be accounted for by such variables as prior maternal abdominal surgery, coexisting fetal anomalies, or improvements in ultrasonographic detection with time. We recommend that the anatomic survey for fetuses at high risk for this condition be performed after 20 weeks' gestation. PMID- 11758022 TI - Prevalence of aneuploidy and additional anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate: a population-based study in Utah. AB - OBJECTIVE: To determine the prevalence of aneuploidy and additional major anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate. METHODS: All cases of cleft lip with or without cleft palate (cleft lip/cleft palate) occurring in Utah from 1995 through 1999 were reviewed by using the Utah Birth Defect Network population-based surveillance system. All pregnancy outcomes are included (stillborn, live born, and termination) in this analysis. RESULTS: Of 263 cases of cleft lip/cleft palate, 72 (27.4%) were unilateral cleft lip, 112 (42.6%) were unilateral cleft lip and cleft palate, 12 (4.6%) were bilateral cleft lip, and 67 (25.5%) were bilateral cleft lip and cleft palate. Fifteen (5.7%) of the 263 fetuses and neonates were aneuploid. One (1.2%) with cleft lip (unilateral and bilateral combined) was aneuploid. Five (4.5%) of the fetuses and neonates with unilateral cleft lip and cleft palate were aneuploid compared with 9 (13.4%) of fetuses and neonates with bilateral cleft lip and cleft palate. In known or presumed euploid fetuses and neonates, additional sonographically occult major anatomic abnormalities occurred in 5 (7.0%) of 71 with unilateral cleft lip, 18 (16.8%) of 107 with unilateral cleft lip and cleft palate, 1 (8.3%) of 12 with bilateral cleft lip, and 12 (20.7%) of 58 with bilateral cleft lip and cleft palate. These abnormalities primarily involved the heart and the central nervous system. CONCLUSIONS: Amniocentesis for karyotype should be offered in all cases of cleft lip/cleft palate because of the risk of aneuploidy. Patients should be counseled that sonographically occult additional anatomic abnormalities might be present with all clefts. PMID- 11758023 TI - Early second-trimester low umbilical coiling index predicts small-for-gestational age fetuses. AB - OBJECTIVE: To evaluate the role of the early second-trimester Doppler velocimetric studies of the umbilical coiling index and umbilical cord cross sectional area as tests for the prediction of small-for-gestational age infants. METHODS: Doppler blood flow studies in 147 singleton pregnancies at risk for delivery of a small-for-gestational-age neonate were performed at 15 +/- 1 (SD) weeks' gestation from the uterine artery, umbilical artery, middle cerebral artery, inferior vena cava, and ductus venosus. Pulsatility index values were calculated for the arteries, and preload index values and systolic-atrial contraction ratios were calculated for the veins. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. The umbilical coiling index was calculated by using sonographic longitudinal views of cord vessels from several segments antenatally and by dividing the total number of helices by cord length (centimeters) postnatally. Small-for-gestational-age neonates were identified when the birth weight was below the 10th percentile for gestational age. RESULTS: Among 147 pregnancies studied, 124 fulfilled the study criteria. Thirty-nine of the neonates were small for gestational age at birth (31.5%). The mean +/- SD gestational age at delivery of the appropriate-for-gestational-age neonates was 39.7 +/- 1.28 weeks, and that of the small-for-gestational-age neonates was 36.4 +/- 2.9 weeks (range, 28-40 weeks). The best single predictor of a small-for gestational-age infant was the coiling index, with sensitivity of 79%, specificity of 86%, a positive predictive value of 72%, and a negative predictive value of 90%. CONCLUSIONS: The umbilical coiling index measured in the second trimester is useful in predicting the birth of a small-for-gestational-age infant and may serve as a marker for subsequent growth restriction. PMID- 11758024 TI - Echo color Doppler findings in postpubertal mumps epididymo-orchitis. AB - OBJECTIVE: To describe echo color Doppler features of mumps epididymo-orchitis in postpubertal boys and men. METHODS: Color Doppler ultrasonographic examinations of the scrotum in 12 patients (14-34 years old) with serologically proven mumps and symptomatic epididymo-orchitis (pain and scrotal swelling) were compared with color Doppler ultrasonographic examinations of the scrotum in 10 healthy control subjects. RESULTS: Clinically evident testicular involvement was bilateral in 1 patient and unilateral in 11 patients (9 left- and 2 right-sided). Four (33.3%) of 12 patients had swelling and a heterogeneous echo texture of the epididymis and hydrocele. Two (16.7%) of 12 patients had swelling of both the epididymis and didymus of the involved side, with a heterogeneous echo texture of the didymus due to hypoechoic, irregularly shaped, confluent intraparenchymal areas. Two (16.7%) of 12 patients had only unilateral mild hydrocele and no testicular abnormalities. In 4 (33.3%) of 12 cases, B-mode ultrasonographic examination did not show any testicular abnormalities or hydrocele. Hydrocele was anechoic in 4 cases and multiseptated in 4. In 12 (100%) of 12 patients, color Doppler and power Doppler ultrasonography showed hypervascularity in the parenchyma of the affected testicle. In 11 patients, spectral Doppler examination of the arteries at the testicular hilum showed a significantly lower mean +/- SD resistive index (0.54 +/- 0.03; range, 0.48-0.57) on the inflamed side compared with the opposite unaffected side (mean, 0.66 +/- 0.04; range, 0.71-0.60) (P < .001). In the patient with bilateral involvement, the mean resistive index values in the right and left testicular arteries were 0.57 and 0.55, respectively. The mean resistive index of the 13 inflamed testicles (0.54 +/- 0.03; range, 0.48-0.57) was significantly different from the mean resistive index values of the right (0.68 +/- 0.03) and left (0.67 +/- 0.04) testicular arteries in healthy control subjects (P < .001). The mean resistive index in the 11 unaffected testicles in our patients (0.66 +/- 0.04; range, 0.71-0.60) was not significantly different from the mean resistive index in healthy control subjects. CONCLUSION. Ultrasonographic findings in mumps orchitis are not specific. Echo color Doppler examination is more sensitive than ultrasonography alone for revealing testicular inflammation. PMID- 11758025 TI - Cardiopulmonary function in rats with lung hemorrhage induced by pulsed ultrasound exposure. AB - OBJECTIVE: To assess cardiopulmonary function in rats exposed to pulsed ultrasound using superthreshold exposure conditions known to produce significant lung hemorrhage. METHODS: In 1 group of 9 anesthetized Sprague-Dawley rats, 5 foci of ultrasound-induced hemorrhage were produced in the left lung of each rat. In a second group of 6 rats, 5 foci of ultrasound-induced hemorrhage were produced in the left and right lungs of each rat. Each lesion was induced using superthreshold pulsed ultrasound exposure conditions (3.1-MHz center frequency, 1.7-kHz pulse repetition frequency, 1.3-micro-second pulse duration, 60-second exposure duration, 39-MPa in situ peak compressional pressure, and 17-MPa in situ peak rarefactional pressure). After exposure, the lungs were fixed in formalin and assessed histologically. The total lesion volume was calculated for each lesion in each lung lobe. Measurements of cardiopulmonary function included assessment of pulsatile arterial pressure, heart rate, end-tidal carbon dioxide, respiratory rate, and arterial blood gases (PCO2 and PO2). Functional data were quantified before (baseline) and 30 minutes after exposure to ultrasound. RESULTS: In the 9 rats that had lesions in only the left lung, the mean (SEM) lesion volume was 97 (13) mm3 and represented about 3.4% of the total lung volume. In the 6 rats that had lesions in both the left and right lungs, the left, right, and total mean lesion volumes, respectively, were 102 (16), 114 (11), and 216 (18) mm3 and represented about 3.7%, 4.2%, and 7.9% of the total lung volume. There were no statistically significant differences in cardiopulmonary measurements between baseline values and values obtained after exposure to ultrasound in the 9 rats exposed on the left lung only. The 6 rats exposed bilaterally had statistically significant differences in arterial pressure (134 +/- 4 versus 113 +/- 9 mm Hg; P= .047) and arterial PO2 (70 +/- 5 versus 58 +/- 4 mm Hg; P = .024) between baseline values and values obtained after exposure to ultrasound. CONCLUSIONS: The severity of ultrasound-induced lesions produced in 1 lung did not affect measurements of cardiopulmonary function because of the functional respiratory reserve in the unexposed lung. However, when both the left and right lungs had ultrasound-induced lesions, the functional respiratory reserve was decreased to a point at which rats were unable to maintain systemic arterial pressure or resting levels of arterial PO2. PMID- 11758026 TI - Doppler measurement of cerebral and lower limb flow during a lower body negative pressure test for predicting orthostatic intolerance. AB - OBJECTIVE: To quantify the cardiovascular response to an orthostatic test for predicting orthostatic intolerance. METHODS: Cerebral and lower limb arterial flow and resistance were assessed by Doppler ultrasonography during lower body negative pressure (7 minutes each at -25 and -45 mm Hg). Cardiovascular deconditioning was induced by 42 days in head-down tilt at -6 degress (7 subjects) and 6-month spaceflights (10 cosmonauts). RESULTS: Orthostatic intolerance during a stand test was observed in 57% of the head-down-tilt subjects and 83% of the cosmonauts. At the lower body negative pressure after head-down tilt and during or after flight, the average cerebral flow velocity and vascular resistance did not change significantly from before head-down tilt and before flight. Conversely, there was a lack of lower limb arterial vasoconstriction (-24% from before head-down tilt and -43% from before flight; P < .01), and the cerebral-femoral flow ratio increased less (-27% from before head down tilt and -52% from before flight; P < .01). The lack of vasoconstriction was more pronounced in intolerant subjects (-25% from before head-down tilt and -48% from before flight) compared with tolerant subjects (-22% from before head-down tilt and -14% from before flight; P > .01). Also, the lack of a cerebral-femoral flow ratio increase was more pronounced in intolerant subjects (-49% from before head-down tilt and -55% from before flight; P < .01) than in tolerant subjects ( 1% from before head-down tilt and -33% from before flight; P < .01). The cerebral flow deficit at the lower body negative pressure before head-down tilt was greater than 8% in 3 of the 4 intolerant head-down-tilt subjects and less than 8% in the 3 tolerant subjects. The 3 cosmonauts who were intolerant after flight had a preflight cerebral flow deficit greater than 8%, whereas the tolerant cosmonaut had a cerebral flow deficit less than 8%. CONCLUSION: Lack of lower limb vasoconstriction and a lower cerebral-femoral flow ratio during lower body negative pressure in disadapted subjects were associated with orthostatic intolerance. A cerebral flow deficit during lower body negative pressure before disadaptation allowed measurement of the predisposition of the subjects to become intolerant. PMID- 11758027 TI - Evaluation of a gel-coupled quantitative ultrasound device for bone status assessment. AB - OBJECTIVE: To evaluate a new gel-coupled calcaneal quantitative ultrasound system, Osteospace (Medilink, Montpellier, France), which was designed to assess the status of bone in the calcaneus. METHODS: The study group consisted of 215 healthy white women aged 20 to 85 years and 51 white women aged 60 to 86 years with osteoporotic fractures. Fifty-two healthy women aged 50 to 85 years were randomly selected from the healthy cohort as the control group. All the women had calcaneal quantitative ultrasonic measurements. The women with osteoporotic fractures and the control group also had proximal femur and lumbar anteroposterior spine bone mineral density measurements using dual X-ray absorptiometry. Bone mineral density was also measured in a subgroup of 54 women at the calcaneus. RESULTS: There was a significant inverse correlation of broadband ultrasound attenuation and speed of sound with age (P < .001). Short term measurement precision values expressed as coefficients of variation were 1.72% for broadband ultrasound attenuation and 0.64% for speed of sound, and standardized short-term precision values were 6.09% for broadband ultrasound attenuation and 3.87% for speed of sound. The correlations between the quantitative ultrasonic parameters and calcaneal bone mineral density were 0.69 (P = .0001) for broadband ultrasound attenuation and 0.45 (P = .0008) for speed of sound. Both quantitative ultrasonic parameters and all bone mineral density measurements of the hip and spine differed significantly between the control and osteoporotic fracture groups (P < .01). Age-, weight-, and height-adjusted odds ratios per SD decrease were as follows: broadband ultrasound attenuation, 1.79; speed of sound, 1.83; spine bone mineral density, 2.34; femoral neck bone mineral density, 1.69; and total hip bone mineral density, 1.85. The areas under the receiver operating characteristic curve for quantitative ultrasound parameters and bone mineral density measurements were close, ranging from 0.75 to 0.80. CONCLUSIONS: This new quantitative ultrasound system can detect age- and menopause-related influences on skeletal status and can discriminate healthy women from those with osteoporotic fractures in a manner comparable with that of bone mineral density measurement by dual X-ray absorptiometry. PMID- 11758028 TI - Sonographic findings of solid and papillary epithelial neoplasm of the pancreas. AB - OBJECTIVE: To evaluate the sonographic findings of solid and papillary epithelial neoplasm of the pancreas, a rare tumor occurring in young women. METHODS: The sonographic findings of 11 cases of pathologically proven solid and papillary epithelial neoplasm of the pancreas were retrospectively evaluated. RESULTS: In 6 cases (55%), combined cystic and solid portions of the masses were observed, whereas only solid-looking masses without anechoic cystic portions were seen in 4 cases (36%). One case (9%) had marginal calcification, consequently, the internal architecture was not evaluated by sonography. Internal echoes were seen in 3 of 6 cystic and solid masses. Septa were seen in 3 cases. Among 11 cases of solid and papillary epithelial neoplasm, tumor margins were well defined in 10, and tumor capsules were detected in 9 (echogenic in 7 and hypoechoic in 2). Calcifications were seen in 3 cases (27%). CONCLUSIONS: The characteristic sonographic findings of solid and papillary epithelial neoplasm were well-encapsulated, cystic, and solid masses, but sometimes the mass was seen as a pure solid-looking mass or had internal septations or calcifications. PMID- 11758029 TI - Organizing posterior fossa hematomas simulating developmental cysts on prenatal imaging: report of 3 cases. AB - OBJECTIVE: We encountered 3 organizing tentorial hematomas simulating posterior fossa lesions such as Dandy-Walker, dermoid, or arachnoid cysts. We sought to correlate the clinical and pathologic features that allow distinction of developmental cysts from hematomas in the posterior fossa on imaging. METHODS. Prenatal sonograms in all fetuses and fetal magnetic resonance scans in 2 of the 3 were reviewed. One case proceeding to term had serial imaging up to age 11 months. Two cases had complete neuropathologic evaluation after termination. Maternal records were reviewed. RESULTS: In each case, the ultrasonographic findings were reminiscent of a developmental cyst but with echogenic debris, a rim, or both. Magnetic resonance imaging suggested tentorial hemorrhage in 2, 1 also with falcine hemorrhage. Serial prenatal and postnatal imaging showed resolution in the surviving case. Pathologically, 2 fetuses had organizing tentorial hematomas causing brain displacement. Calcifications, white matter damage, germinal matrix hemorrhage, and brain stem necrosis were also present. One mother had von Willebrand disease. CONCLUSIONS: Tentorial hematomas, with or without maternal coagulopathy, should be considered in the prenatal ultrasonographic diagnosis of cystlike posterior fossa abnormalities containing echogenic material. Fetal magnetic resonance imaging can suggest blood products. Hypoxic-ischemic brain damage may be concurrent; however, resolution of the hematoma, with no apparent neurologic sequelae, can occur. PMID- 11758030 TI - Endosonographic features of a granular cell tumor of the colon. PMID- 11758031 TI - Fibroma of the testicular tunics: an unusual extratesticular intrascrotal mass. PMID- 11758032 TI - Thyroid gland rupture after blunt neck trauma: sonographic and computed tomographic findings. PMID- 11758033 TI - Transvaginal ultrasonographic depiction of a Gartner duct cyst. PMID- 11758034 TI - Prenatal diagnosis of intra-abdominal mature testicular teratoma. PMID- 11758035 TI - Ultrasonographically guided thyroid biopsy. PMID- 11758036 TI - Social categorization, self-esteem, and the estimated musical preferences of male adolescents. AB - The authors investigated the intergroup processes of male adolescents within the context of social identity theory (SIT; H. Tajfel, 1978; H. Tajfel & J. C. Turner, 1979). The participants were English male adolescents (age = 14-15 years). They estimated in-group and out-group musical preferences and evaluated the in-group and out-group along a series of scales. The results showed in-group favoritism effects along the musical preference and evaluative dimensions. The participants reported greater liking for the in-group. Compared with the out group, they associated the in-group more with positively stereotyped music and less with negatively stereotyped music. Compared with the out-group, they rated the in-group as more fun, more masculine, more sporty, less boring, less snobbish, and less weird. The participants with lower levels of self-esteem showed greater differentiation between groups and greater derogation of the out group. The results supported the predictions of SIT and demonstrated the applicability of SIT for the study of adolescent behavior. PMID- 11758037 TI - Ethnic attitudes in relation to ethnic pride and ethnic differentiation. AB - A comparison of 4 subsamples with the Ethnic Identity Scale (developed for the present study) yielded 2 relatively independent facets of ethnic identity: ethnic pride and belonging (EP) and ethnic differentiation (ED). First, the distinction between EP and ED increased understanding of how age and immigration status affect changes in ethnic identity. In a comparison of Estonians living in Sweden with those living in Estonia, only ED was affected by emigration and contacts with other ethnic groups, although both EP and ED were positively correlated with age. Second, the distinction between EP and ED increased understanding of earlier and seemingly contradictory findings about the connection between ethnic identity and ethnic attitudes. In the present study, EP was not correlated with ethnic attitudes, but, for 2 majority groups, ED was positively correlated with negative evaluations of out-groups. The authors also discuss the role of group status and relationships with the target nation in understanding the relationship between ethnic identity and ethnic attitudes. PMID- 11758038 TI - Interactive effects of characteristics of defendant and mock juror on U.S. participants' judgment and sentencing recommendations. AB - The authors examined the effects of interactions (a) between defendant attractiveness and juror gender and (b) between defendant race and juror race on judgment and sentencing among 207 Black, Hispanic, and White participants in the United States. After reading a vehicular-homicide vignette in which the defendant's attractiveness and race varied, the participants rated guilt and recommended sentences. The women treated the unattractive female defendant more harshly than they treated the attractive female defendant; the men showed an opposite tendency. The Black participants showed greater leniency when the defendant was described as Black rather than White. The Hispanic participants showed an opposite trend, and the White participants showed no race-based leniency. The findings on racial effects were consistent (a) with in-group favorability bias among the Black participants and (b) with attribution effects unrelated to race among the White participants. PMID- 11758039 TI - Helping norms in relation to religious affiliation. AB - The authors used vignettes to solicit each participant's estimate of the likelihood of help and his/her recommendation for or against helping a student who needed to borrow another student's class notes. The study had a 2 (Hindu vs. Muslim participant) x 2 (participant's gender) x 2 (liking vs. disliking relationship) x 2 (justified vs. unjustified need for help) x 2 (low vs. high cost of helping) factorial design with 15 participants per cell. Estimated likelihood of help was higher among the female than among the male participants, with the liking than with the disliking relationship, and with the low rather than with the high cost of helping. The Hindu participants gave lower estimates of the likelihood of help than did the Muslim participants with the disliking relationship and with the unjustified need for help. Intracommunal helping, irrespective of contextual variations, may have been a stronger social norm for the Muslim than for the Hindu participants, probably because of the former's minority status in India and, more important, the Islamic prescription of communal brotherhood. Even though both communities are deemed collectivist, the Indian Muslim participants' helping norms appeared to be more obligation oriented and less option oriented than those of the Indian Hindu participants. PMID- 11758040 TI - Associations between religious behavior and attitude to Christianity among Australian Catholic adolescents: scale validation. AB - In a sample of 1,166 Catholic high school students (age = 13-18 years), the author used confirmatory factor analysis to validate a 30-item instrument that assesses 6 dimensions of attitude to Christianity (viz., attitude to prayer, attitude to God, attitude to Jesus, attitude to the Bible, attitude to Christian practice, attitude to social justice). Goodness-of-fit indices for the proposed measurement model revealed that the model fitted the data very well, thus confirming the instrument's structure. A correlation analysis revealed associations between religious behavior and attitude to Christianity. PMID- 11758041 TI - Social judgment of abortion: a black-sheep effect in a Catholic sheepfold. AB - French Catholic participants (N = 340) with high or low religious identification read 1 of 8 scenarios presented as an interview with a female target 2 months after she had had an abortion. The experimental device varied situational pressure (pressure vs. no pressure), the target's religious social identity (Catholic vs. neutral), and the consequences of abortion for the target (positive vs. negative). The participants then rated the acceptability of the target's decision. The participants judged abortion more negatively in the no-pressure condition. Moreover, the participants with high religious identification judged abortion more negatively than did those with low religious identification. In partial support of a black-sheep effect, the participants with high religious identification judged the Catholic target more negatively than they judged the neutral one in some conditions (pressure, negative consequences). In other conditions (no pressure, both positive and negative consequences), the participants with low religious identification judged the Catholic target more positively than they judged the neutral one. PMID- 11758042 TI - Relationships between drinking and type of practice among U.S. female and male attorneys. AB - The author investigated the relationship between drinking and type of practice among U.S. attorneys. Participants were attorneys from 2 large midwestern cities, chosen through stratified random sampling from bar-association membership lists. Type of law practice was related to whether the participants drank in business related situations but not to the frequency or the quantity of consumption. The participants in solo, corporate, or government practices were more likely than were those in private group practices to report no business-related drinking in the past 30 days. Female and male attorneys in similar practices reported similar abstention rates and quantities of consumption in business situations, suggesting that occupational norms were strongly salient for both genders. Criminal trial work was related to drinking only for the women. Results are discussed in terms of the influence of occupational culture on drinking. PMID- 11758043 TI - Sex-linked carrying styles and the attribution of homosexuality. AB - We used pairs of slides showing 3 women and 3 men displaying 2 sex linked carrying styles to examine differences in the attribution of homosexuality as a consequence of behavioral displays that are either sex typical or sex atypical. We hypothesized that the participants would be less likely to view targets displaying sex-typical behaviors as gay men or as lesbians. Each of 2 groups of U.S. university students rated targets in 6 slides on homosexuality and 3 other traits. The mean difference in rated homosexuality for typical versus atypical carrying styles was small but statistically significant. Thus, the results provide some empirical support for the common belief that effeminate men and masculine women are more likely to be seen as homosexual, at least by U.S. university students. PMID- 11758044 TI - Horizontal and vertical individualism and collectivism among college students in the United States, Taiwan, and Argentina. AB - Among college students in the United States, Taiwan, and Argentina, the author examined the strength of 4 cultural patterns (horizontal collectivism, vertical collectivism, horizontal individualism, vertical individualism; H. C. Triandis, 1995). A 3-group confirmatory factor analysis established the measurement equivalence among the 3 samples before the comparison. The Taiwanese and the Argentine samples were more vertically collectivist than the U.S. sample. The U.S. and the Taiwanese samples were more vertically individualistic than the Argentine sample. The U.S. sample was more horizontally individualistic than the Argentine sample, which, in turn, was more horizontally individualistic than the Taiwanese sample. PMID- 11758045 TI - Psychological reactance: factor structure and internal consistency of the Questionnaire for the Measurement of Psychological Reactance. AB - Psychological reactance, the theory that people resist attempts to constrain either their thoughts or their behaviors (J. W. Brehm, 1966), has been an influential concept in social psychology. In an attempt to measure reactance, J. Merz (1983) developed the Questionnaire for the Measurement of Psychological Reactance (QMPR). Subsequent researchers (S.-M. Hong & R. Ostini, 1989; R. K. Tucker & P. Y. Byers, 1987) have debated both the exact factor structure and the psychometric stability of the QMPR. In the present study, 898 undergraduates completed the QMPR. Factor analysis suggested that psychological reactance is multidimensional. The authors found 3 factors underlying the QMPR, but the QMPR provided unreliable estimates for each of those factors. According to the results, the QMPR as currently written is psychometrically unsatisfactory. PMID- 11758046 TI - The effect of abortion restrictions on the timing of abortions. AB - This paper uses data on the distribution of abortions by weeks of gestation to examine the relationship between abortion restrictions and the timing of abortions. State-level data from 1974 to 1997 indicate that adoption of parental involvement laws for minors or enforcement of mandatory waiting periods is positively associated with the post-first trimester percentage of abortions. However, autocorrelation-corrected specifications indicate that enforced parental involvement laws increase the share of later-term abortions by lowering the first trimester abortion rate rather than by delaying abortions. Medicaid funding restrictions generally do not have a significant effect on the timing of abortions in our results. PMID- 11758047 TI - Scale and scope in drug development: unpacking the advantages of size in pharmaceutical research. AB - Drug development performance is examined using data on clinical research projects of 10 pharmaceutical companies. In contrast to previous work on the discovery phase of pharmaceutical R&D we find a strong correlation between the diversity of firms' development efforts and the success probability of individual projects, but no effect of scale per se. Large firms' superior performance in drug development appears to be driven by returns to scope rather than returns to scale. Scope is confounded with firm fixed effects, however, suggesting an important role for inter-firm differences in the organization and management of the development function. PMID- 11758048 TI - The demand for consumer health information. AB - Using data from an evaluation of a community-wide informational intervention, we modeled the demand for medical reference books, telephone advice nurses, and computers for health information. Data were gathered from random household surveys in Boise, ID (experimental site), Billings, MT, and Eugene, OR (control sites). Conditional difference-in-differences show that the intervention increased the use of medical reference books, advice nurses, and computers for health information by approximately 15, 6, and 4%. respectively. The results also suggest that the intervention was associated with a decreased reliance on health professionals for information. PMID- 11758049 TI - Screening and preventable illness. AB - If an agent does not discount the future at a constant rate, as in some forms of myopia, her optimal strategy is unattainable without some commitment device. We apply this familiar idea to a model of screening and disease prevention, and explore how financial incentives can correct suboptimal health choices. In general, myopia need not imply under-screening. While the optimal intervention for prevention effort is a state-invariant subsidy, the optimal intervention for screening may involve a tax or a subsidy. When screening and prevention are coincident, a simple and practical subsidy equal to one minus the discount factor to both screening and intervention is indicated. PMID- 11758050 TI - Slippery when wet: the effects of local alcohol access laws on highway safety. AB - Using detailed panel data on local alcohol policy changes in Texas, this paper tests whether the effect of these changes on alcohol-related accidents depends on whether the policy change involves where the alcohol is consumed and the type of alcohol consumed. After controlling for both county and year fixed effects, we find evidence that: (i) the sale of beer and wine may actually decrease expected accidents; and (ii) the sale of higher alcohol-content liquor may present greater risk to highway safety than the sale of just beer and wine. PMID- 11758051 TI - Statistical discrimination in health care. AB - This paper considers the role of statistical discrimination as a potential explanation for racial and ethnic disparities in health care. The underlying problem is that a physician may have a harder time understanding a symptom report from minority patients. If so, even if there are no objective differences between Whites and minorities, and even if the physician has no discriminatory motives, minority patients will benefit less from treatment, and may rationally demand less care. After comparing these and other predictions to the published literature, we conclude that statistical discrimination is a potential source of racial/ethnic disparities, and worthy of research. PMID- 11758052 TI - The incentive effects of the Medicare indirect medical education policy. AB - Medicare provided teaching hospitals with US$ 5.9 billion in supplemental graduate medical education (GME) payments in 1998. These payments distort input and output prices and provide teaching hospitals with incentives to hire residents, close beds, and admit more Medicare patients. The structure of the GME payment policy creates substantial variation in input and output prices between teaching hospitals. We examine the extent to which hospitals responded to these financial incentives using a panel data set of 3,900 hospitals, including over 900 teaching hospitals. We find that teaching hospitals did hire residents and close beds in response to the Medicare policy, but did not increase Medicare admissions or alter their use of registered nurses (RNs). PMID- 11758053 TI - An examination of flexible spending accounts. AB - This paper develops a framework for analyzing flexible spending account (FSA) participation and usage. We explore patterns of FSA usage using data from a benefits firm for 1996 including an examination of types of FSA expenditures and their timing. We estimate some simple econometric models of the participation decision and also the decision of how much to put into an FSA. Several pieces of evidence suggest that much of an FSA election amount is based on foreknowledge of expenditures. We also find that participants tend to spend their election amount early, thus obtaining an interest-free loan. PMID- 11758054 TI - Regulatory restrictions on selective contracting: an empirical analysis of "any willing-provider" regulations. AB - "Any-willing-provider" (AWP) laws compel managed care plans to accept any provider willing to accept the plan's terms and conditions, potentially undermining managed care's ability to constrain spending. However. AWP laws potentially respond to inefficient risk-selection by providers of managed care. With risk selection, observed reductions in expenditures in the managed care sector may be offset by increases in the fee-for-service (FFS) sector, with no net decrease. This paper uses panel data on state expenditures to compare per capita spending levels in states with and without AWP laws. The results indicate that expenditures are higher when AWP laws are enacted. PMID- 11758055 TI - The welfare impact of HMO mergers. AB - This paper estimates the welfare consequences of HMO mergers using data from California's small-group market. The analysis estimates the parameters from a differentiated products demand system. The parameters are then used to simulate the effects of several HMO mergers by solving for the Nash equilibrium in prices under different ownership structures. Even small mergers in moderately concentrated markets can result in significant consumer surplus reductions. However, these welfare losses can be offset by large efficiency gains. The welfare consequences of HMO mergers turn less upon demand-side considerations than on the health plan's ability to realize efficiencies. PMID- 11758056 TI - Alcohol, marijuana, and American youth: the unintended consequences of government regulation. AB - This paper analyzes the impact of increases in the minimum drinking age on the prevalence of alcohol and marijuana use among high school seniors. The empirical analysis is based on a large sample of students from 43 states over the years 1980-1989. We find that increases in the legal minimum drinking age did slightly reduce the prevalence of alcohol consumption. We also find, however, that increased legal minimum drinking ages had the unintended consequence of slightly increasing the prevalence of marijuana consumption. Estimates from a structural model suggest that this unintended consequence is attributable to standard substitution effects. PMID- 11758058 TI - Systemic pulmonary artery shunt using a bovine mesenteric venous graft in newborns. AB - A new bovine mesenteric venous graft 3 or 4 mm in diameter was used for performing systemic pulmonary artery shunts in six cyanotic newborns (aged 2 to 30 days) from March 1997 onward. Clinical and echocardiographic studies proved that all shunts were patent and functioning well after an average of 8.8 months despite no postoperative anticoagulation or antiplatelet regimen. Histological examination of two grafts explanted at the time of bidirectional cavopulmonary anastomosis showed no dense fibrotic mural infiltration, calcification, or anastomotic hyperplasia. Bovine mesenteric venous grafts can be used for the construction of systemic pulmonary artery shunts with advantages similar to that of human vein allografts, such as the facility of implantation, good short- and mid-term patency, easy takedown, and avoidance of complications presumably specific to polytetrafluoroethylene. PMID- 11758057 TI - Heparin-bonded cardiopulmonary bypass circuits reduce bleeding and transfusion requirements in proximal aortic surgery. AB - BACKGROUND: Methods to improve hemostasis in aortic surgery continue to evolve. Use of heparin-bonded cardiopulmonary bypass circuits (HBC) has been shown previously to effectively reduce bleeding and improve outcomes in coronary and valve operations. OBJECTIVE: To evaluate the impact of HBC on bleeding and transfusion requirements in proximal aortic surgery. METHODS: Data on 140 consecutive patients undergoing 144 operations of the proximal aorta were collected. Between July 1987 and July 1994, conventional cardiopulmonary bypass circuits (CONV) were used (n = 53). In July 1994, we switched to "tip-to-tip" HBC (n = 91). This study compared clinical outcomes and transfusion requirements between these two groups. RESULTS: Indications for surgery, baseline characteristics, and operative profile of the study groups were similar. Overall operative mortality and reoperation for bleeding were 9% and 13%, respectively. Compared with CONV, use of HBC was associated with decreased mortality (3% vs 18%, p = 0.004), reoperation for bleeding (7% vs 24%, p = 0.005), and hospital length of hospital stay (10 +/- 11 vs 20 +/- 30 days, p = 0.002). Although the incidence of allogeneic blood transfusion was similar (HBC 75% vs CONV 87%, p = 0.12), the magnitude of blood products utilization was much lower in the HBC group (total blood products per patient: 24 +/- 29 vs 49 +/- 47 donor units, p = 0.0002). In the multivariate analyses, use of HBC was identified as an independent predictor of reduced mortality, morbidity, and reduced magnitude of allogeneic blood transfusions. CONCLUSION: Use of HBC in proximal aortic surgery resulted in reduced bleeding and blood transfusion, improving clinical outcomes. Undoubtedly, multiple factors account for the overall improved results. However, use of HBC is an important component of an overall blood conservation strategy. PMID- 11758059 TI - A xiphoid approach for minimally invasive coronary artery bypass surgery. AB - BACKGROUND: The premise for adopting minimally invasive cardiac surgery techniques for myocardial revascularization is to reduce the patient's morbidity without compromising the efficacy of conventional coronary artery bypass. However, opening the pleura has been a limitation of using these approaches. AIM: We used the xiphoid approach as an alternative to opening the pleura and to minimize pain after minimally invasive coronary artery bypass surgery. METHODS: We review our surgical experience in 55 patients who underwent minimally invasive direct coronary artery bypass (MIDCAB) surgery through a xiphoid approach between October 1997 and August 1999. Thoracoscopy (n = 31) or direct vision (n = 24) were used for internal mammary artery (IMA) harvesting. Mean patient age was 67 +/- 10 years and 65% were men. The mean Parsonnet score was 23 +/- 10. Performed anastomoses included left IMA (LIMA) to the left anterior descending (LAD) artery (n = 53), LIMA-to-LAD and saphenous vein graft from the LIMA to the right coronary artery (n = 1), and LIMA-to-LAD and right IMA (RIMA) to right coronary artery (n = 1). RESULTS: Postoperative complications included atrial fibrillation (12%), acute noninfectious pericarditis (12%), and acute renal failure (5%). Mean postoperative length of stay was 4 +/- 2 days. Angiography was performed in 16 patients and demonstrated excellent patency of the anastomoses. There was no operative mortality. Actuarial survival was 98% in a mean follow-up period of 11 +/- 5 months. CONCLUSIONS: Minimally invasive coronary artery bypass can be performed safely through a xiphoid approach with low morbidity, mortality, and a relatively short hospital stay. PMID- 11758060 TI - Off-pump myocardial revascularization using arterial conduits without cardiopulmonary bypass. AB - OBJECTIVE: The feasibility of myocardial revascularization via a median sternotomy with arterial conduits, without and with cardiopulmonary bypass (CPB), was evaluated. MATERIAL AND RESULTS: From May 21, 1997, to November 30, 1999, 721 patients had myocardial revascularization without CPB via median sternotomy using at least two arterial conduits. The procedure was performed without CPB in 322 patients (Group A); the remaining 399 patients (Group B) underwent the same operation with the aid of CPB. Group A patients were older, with a higher ejection fraction and less redo than Group B. There was no early death in Group A versus nine (2.3%) patients in Group B (p < 0.02). Incidence of cerebrovascular accident (CVA) and acute myocardial infarction (AMI) were similar in both groups. Early major events incidences were 1.2% versus 8.0% (p < 0.001) in Groups A and B, respectively. Postoperative angiographic controls showed a cumulative patency rate of 98.4% and a perfect patency rate of 96.7%. After 30 months, Groups A and B showed an actuarial survival of 98.1 +/- 0.7 and 96.5 +/- 2.8 (p = ns) and an event-free survival of 96.6 +/- 1.0 and 96.5 +/- 2.8 (p = ns), respectively. CONCLUSION: Myocardial revascularization without CPB using arterial conduits can be accomplished with the same quality of results obtained with the use of CPB. PMID- 11758061 TI - Robotically assisted coronary artery bypass grafting: a prospective single center clinical trial. AB - AIM: This prospective study was performed as a Phase 1 Food and Drug Administration clinical trial to assess the safety and feasibility of robotically assisted coronary artery bypass grafting (CABG). METHODS: Eighteen patients undergoing elective CABG were enrolled in this study. Full sternotomy was performed in 17 of 18 patients, while cardiopulmonary bypass and cardioplegic arrest was used in all cases. Robotically assisted CABG of the left internal thoracic artery (LITA) to the left anterior descending artery (LAD) was performed through three ports using a robotically assisted microsurgical system. Conventional techniques were used to perform all other grafts. Blood flow in the LITA graft was measured in the operating room, and when necessary, angiography was performed. Six weeks after the operation, all patients underwent selective coronary angiography of the LITA graft. RESULTS: Robotically assisted coronary artery anastomoses were successfully completed in all patients. Blood flow through the LITA graft was adequate in 16 of 18 patients (89%). The two inadequate grafts were revised successfully by hand. Six weeks after the operation, angiography demonstrated a graft patency of 100% (13 of 13). Mean follow-up has been over 190 days. All patients remain New York Heart Association Angina Class I. CONCLUSION: Robotic assistance represents an enabling technology that may allow the surgeon to perform endoscopic coronary artery anastomoses. Further clinical trials are needed to explore the clinical potential and value of robotically assisted CABG. PMID- 11758062 TI - Multivessel off-pump coronary bypass with the Octopus experience in 226 patients. PMID- 11758063 TI - Transmyocardial laser revascularization in the treatment of myocardial ischemia. AB - Since 1990, over five thousand patients worldwide have undergone transmyocardial laser revascularization (TMR) for the treatment of myocardial ischemia due to end stage coronary artery disease. Recently four prospective randomized controlled clinical trials have reported their results in comparing TMR to maximal medical therapy. All of the trials demonstrated that TMR provided notable relief of angina when compared to medical management. Additional objective data in the form of exercise tolerance and myocardial perfusion scanning are used to support the symptomatic improvement. Although the trials are similar, they are not identical, and this review provides an update and comparison of their results. PMID- 11758064 TI - Thoracoscopic IMA takedown. AB - In recent years, the field of minimally invasive cardiac surgery has grown rapidly beginning with the MIDCAB operation and evolving toward totally endoscopic coronary artery bypass grafting (CABG). It promotes the goal of decreasing surgical trauma while maintaining surgical efficacy. For MIDCAB, a limited anterior thoracotomy or mediastotomy have been proposed to harvest the internal mammary artery (IMA). However, complete graft harvesting of the IMA is difficult under direct vision in these circumstances and may necessitate costal resection and important chest wall retraction. Additionally, it carries the potential risk of kinking or coronary steal syndrome. Thoracoscopic harvesting of the IMA avoids these hazards. It permits complete dissection from the subclavian artery to the sixth inter-costal space (ICS) with section of all collateral branches issuing from the IMA without any traumatic retraction. The technique of IMA takedown described herein has been used regularly by us since 1995. Our current experience shows that it is safe and reproducible after a reasonable period of training. Furthermore, in the objective of performing a totally endoscopic and/or robotic CABG, thoracoscopic IMA takedown would be a prerequisite. PMID- 11758065 TI - Focal angiogenic therapy for myocardial ischemia. AB - BACKGROUND: Therapeutic angiogenesis, which involves the administration of angiogenic cytokines to stimulate collateral formation and improve myocardial perfusion, is being tested as an alternative treatment for patients with medically intractable angina who are no longer candidates for conventional revascularization techniques. METHODS: Administration of recombinant protein formulations for these growth factors and transfection of the DNA itself have proven effective in animal models. At present, transfection of the DNA (gene therapy) appears preferable in that a single administration achieves a prolonged but transient, localized exposure of the ischemic tissues to the angiogen. The important technical aspects of surgical gene therapy via a mini thoracotomy incision are described. RESULTS: Four Phase I clinical trials of angiogenic therapy recently have been reported, two involving administration of the recombinant protein combined with coronary bypass and two involving gene therapy alone. These studies have shown that this approach is relatively safe; the early evidence of efficacy is encouraging. The largest study reported six-month follow up on 30 patients who received plasmid DNA for vascular endothelial growth factor 165 (VEGF165) and documented improvement in angina, treadmill exercise tolerance, and myocardial perfusion in the majority of patients studied. CONCLUSIONS: These preliminary results will need to be supported by randomized clinical trials in which angiogenic therapy alone is compared to standard medical therapy or a placebo. Catheter-based intramyocardial gene transfer and combined coronary arterial bypass grafting or transmyocardial laser revascularization plus gene therapy trials are also underway. If proven effective, angiogenic therapy may provide a relatively noninvasive modality for revascularization of ischemic myocardium not amenable to current techniques. PMID- 11758066 TI - Limited access left thoracotomy for reoperative coronary artery disease: on or off pump. AB - Between 1971 and 1988 left thoracotomy was performed on pump for selected reoperations. Since 1993, 92 patients were operated on with a limited approach and an increased number of cases were done off pump (70 patients). The purpose of this paper is to describe the transition of our operative techniques from on pump to off pump for reoperative coronary patients. From 1995 to 1999, 22 patients (Group 1) were operated on pump and 70 patients (Group II) off pump; 86 of 92 (93.5%) had reoperations. The demographic data were similar in these two groups regarding age, gender, ejection fraction, and total number of grafts performed. In this study 92 patients had a crude mortality of 4.3%. Limited access thoracotomy provides safer reoperation than previously (1971-1988) with an improved on or off pump (4.5% vs. 4.3%) mortality, compared to the on pump mortality of 10% between 1971-1988. Off-pump operations are performed with increasing frequency and with the same risk and less postoperative complications. PMID- 11758067 TI - Port-access minimally invasive CABG: techniques and results. PMID- 11758068 TI - Reoperative coronary surgery with and without cardiopulmonary bypass. AB - BACKGROUND: Reoperative coronary surgery without cardiopulmonary bypass (CPB) was analyzed to evaluate the technical profile of the patients studied and the benefit from this technique. MATERIAL AND METHODS: From November 21, 1994 to May 20, 1999, 166 patients had reoperative coronary surgery, 112 patients (Group A) with and 54 patients (Group B) without CPB. Median sternotomy was used in all the patients in Group A and in 13 patients in Group B. The remaining had a LAST (37 patients) or a posterolateral thoracotomy (4 patients). RESULTS: Anastomoses per patient were 2.4 +/- 0.8 in Group A and 1.1 +/- 0.4 in Group B (p < 0.001). When a single graft was needed, CPB was not used in 82.8% of the cases. However, when more than one graft was required, CPB was not used in only 5.6% of the cases. When a single territory had to be grafted, CPB was not used in 76.6% of the patients. If two territories were grafted, only 6.8% of the patients were in Group B, whereas no patient who needed a graft in all the three territories was in Group B. Overall mortality was 3.6% cerebrovascular accident (CVA) and acute myocardial infarction (AMI) incidence were 0.6% and 1.8%, respectively, and were similar in both groups. Incidence of early major events (overall 8.4%) was not different between groups. CONCLUSIONS: The primary endpoints (mortality, CVA rate, and AMI) were similar in both groups, but patients in Group B were less complicated. However, patients in the two groups were not the same, as the technical profile was quite different. As our results were similar to those obtained in the first operation, we think that consideration of different surgical possibilities, depending on territory to be grafted, will improve the results of redo coronary surgery, making them similar to those obtained in the first operation. PMID- 11758069 TI - Are the new Lipid Management Guidelines good for Australia's health? PMID- 11758070 TI - Chronic pain in children. PMID- 11758071 TI - Acute myocardial infarction: improving quality of care. PMID- 11758072 TI - Breaking the back of back pain. PMID- 11758073 TI - Cost-effectiveness of prescribing statins according to pharmaceutical benefits scheme criteria. AB - OBJECTIVES: (i) To analyse how well Pharmaceutical Benefits Scheme (PBS) criteria for prescribing lipid-lowering therapy identify people most at risk of coronary heart disease (CHD); and (ii) to determine the cost-effectiveness of primary prevention therapy with pravastatin according to these criteria in Australia. DESIGN: (i) Analysis of targeting of CHD risk according to PBS criteria; (ii) cost-effectiveness analysis for pravastatin as primary preventive therapy (40 mg/day), with a 20-year projection from 1999. PARTICIPANTS: (i) Men and women aged 25-69 years from the 1989 National Heart Foundation Risk Factor Prevalence Survey; (ii) Australian men and women, aged 25-85 years, excluding those with diabetes and existing CHD. MAIN OUTCOME MEASURES: (i) Proportion eligible for lipid lowering treatment according to PBS criteria within 15-year risk of CHD mortality groups; (ii) average net cost in Australian dollars ($) per year of life saved (YOLS), with 80% uncertainty ranges (UR). RESULTS: (i) PBS criteria do not adequately identify those most at risk of CHD, as only 61% of Australians (aged 25-69 years) with a greater than 10% 15-year risk of CHD mortality were eligible for treatment; and 11% of those at low risk of CHD mortality (< 2.5% over 15 years) were eligible for treatment. (ii) Cost-effectiveness of treatment according to PBS criteria was estimated at $110,000 (80% UR, $96,000-$150,000) per YOLS for men and $87,000 (80% UR, $80,000-$130,000) per YOLS for women. As an indicator of the likely recurrent annual costs, total first-year treatment costs (excluding the costs of non-compliers) were estimated at $940 million. Assuming compliance of 50%, cost-effectiveness of treatment was markedly improved using 32.5% 15-year risk of CHD mortality as a cut-off, with ratios of $31,000 (80% UR, $27,000-$40,000) per YOLS for men and $39,000 (80% UR, $33,000-$53,000) per YOLS for women. First-year treatment costs of $940 million were the same as treating according to PBS criteria, but absolute health impact in terms of deaths averted and years of life saved was more than doubled. CONCLUSIONS: While PBS criteria do target patients at risk of CHD, there is room for improvement in identifying those most at risk of CHD, and treatment according to PBS criteria is not likely to be the most cost-effective. For optimal cost-effectiveness, targeting of therapy for primary CHD prevention needs to be based on population-specific, multivariable risk. PMID- 11758074 TI - The effects of quality improvement interventions on inhospital mortality after acute myocardial infarction. AB - OBJECTIVE: To evaluate the effects of quality improvement interventions on inhospital mortality after admission for acute myocardial infarction (AMI). DESIGN: Before-and-after study (with concurrent controls) based on hospital discharge data from a routinely maintained, administrative database. SETTING: All Queensland public hospitals, July 1991 - June 1999. STUDY POPULATION: Patients with AMI admitted through the emergency department. INTERVENTION: Development and promulgation of clinical practice guidelines at one hospital, combined with regular audit and feedback, commencing November 1995. MAIN OUTCOME MEASURES: Inhospital mortality (adjusted for age, sex and comorbidities) for four-year periods before (1991-92 to 1994-95) and after (1995-96 to 1998-99) initiation of quality improvement interventions. RESULTS: Before the intervention, the adjusted odds ratio (OR) for inhospital death at the intervention hospital was about the same as at other public hospitals (adjusted OR, 0.99; 95% CI, 0.80-1.24), but was more than 40% lower after the intervention (adjusted OR, 0.59; 95% Cl, 0.45 0.78). After the intervention, the risk of death at the intervention hospital was lower compared with hospitals with cardiologists as admitting practitioners (adjusted OR, 0.63; 95% CI, 0.48-0.83), with onsite revascularisation facilities (adjusted OR, 0.66; 95% CI, 0.49-0.88), and with large numbers (> or = 250 per year) of annual admissions of patients with AMI (adjusted OR, 0.72; 95% CI, 0.54 0.97). CONCLUSIONS: Quality improvement interventions lower the risk of inhospital death in patients with AMI. Implementation of such interventions in all hospitals may confer a risk of death lower than that achieved by admitting all patients under the care of cardiologists, or to hospitals with revascularisation facilities or a high volume of admissions of patients with AMI. PMID- 11758075 TI - Lipid lowering and coronary heart disease risk: how appropriate are the national guidelines? AB - OBJECTIVE: To assess the effectiveness of current Australian guidelines for prescribing lipid-lowering drugs in identifying high-risk individuals in primary prevention of coronary heart disease. DESIGN AND SETTING: Coronary heart disease risk profiles were obtained for 280 consecutive patients dispensed lipid-lowering drugs in rural Victoria. Their 10-year absolute risk of coronary heart disease was determined using the Framingham formula. PATIENTS were categorised according to their eligibility for lipid-lowering drugs as defined by current Pharmaceutical Benefits Scheme (PBS) and National Heart Foundation (NHF) guidelines. PATIENTS: Complete data were available for 230 patients dispensed lipid-lowering drugs. Of these, the 138 patients (60%) with no history of vascular disease are the subjects of our study. MAIN OUTCOME MEASURES: Proportion of patients with various 10-year coronary heart disease thresholds (15%, 20% and 30%), compared with their eligibility for lipid-lowering drugs based on Australian PBS and NHF guidelines. RESULTS: Twenty-six per cent of patients with no history of vascular disease who are currently dispensed lipid-lowering drugs do not fulfil PBS guidelines for treatment. Of patients conforming with PBS guidelines as suitable for lipid-lowering drugs, 39% (95% CI, 30%-49%) had a 10 year risk of coronary heart disease of less than 15%. A similar proportion (41% [95% CI, 32%-50%]) had a 10-year risk of coronary heart disease of less than 15%, but were eligible for lipid-lowering drugs according to NHF guidelines. Adherence to PBS and NHF guidelines in patients currently dispensed lipid-lowering drugs would result in as many as 14% (95% CI, 8%-21%) and 7% (95% CI, 3%-12%) of patients, respectively, not being eligible for treatment, despite having a 10 year risk of coronary heart disease greater than 15%. CONCLUSIONS: Australian guidelines for prescribing of lipid-lowering drugs are poor discriminators of absolute risk of coronary heart disease in primary prevention. Strategies based on the continuous relationship between risk-factor intensity and absolute coronary heart disease risk, such as the Framingham risk estimates, provide a more rational basis for formulating treatment guidelines. PMID- 11758076 TI - Management of chronic pain in children. AB - OBJECTIVES: To describe the demography, clinical characteristics, treatment, functional limitations and outcomes of patients referred to a paediatric multidisciplinary pain clinic. DESIGN: Prospective data collection, descriptive study. PATIENTS AND SETTING: Tertiary referral centre pain clinic (Royal Children's Hospital, Melbourne) over two years (March 1998 - March 2000). MAIN OUTCOME MEASURES: Pain profile; functional disability (school absenteeism, sleep disturbance and inability to perform sport); treatments received; outcome. RESULTS: 207 patients (mean age, 13.1 years; 73% females; 29% rural residents) were referred in the two years. Concomitant medical conditions were present in 106/207 (51%) patients, the commonest being cerebral palsy or spasticity (22 patients) and malignancy (18). Complex regional pain syndrome was diagnosed in 44 patients. Functional disability due to pain included school absenteeism (95% of school attenders), sleep disruption (71% of all patients) and inability to perform sport (90% of those able to participate in sport previously). Of the 105 patients who missed five or more days of school because of pain, 93 attended school regularly after treatment. Sleep disturbance improved in 129/146 (88%) patients, and 129/147 (88%) resumed sporting activity after multidisciplinary intervention. Outcome was classified as good in 134 patients (65%), moderate in 32 (15%) and poor in 16 (8%). CONCLUSIONS: Chronic pain in children and adolescents often results in considerable functional disability. Functional improvement can be achieved using a multidisciplinary approach to pain management in children. PMID- 11758077 TI - Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin. AB - We report the first instance in Australia of treatment failure due to a strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin--heteroresistant vancomycin-intermediate S. aureus (hVISA). The infection occurred in a 41-year-old man with multiple risk factors. No transmission of the organism to other patients or the environment was detected. This case may herald the beginning of a new phase of staphylococcal resistance in Australia. PMID- 11758078 TI - Meningitis and septicaemia in a child caused by non-typable Haemophilus influenzae biotype III. AB - Since vaccination against Haemophilus influenzae type b (Hib) became widespread, other strains of H. influenzae have become more common than Hib as causes of disease in vaccinated children. A four-month-old, appropriately vaccinated infant presented with meningitis and septicaemia caused by H. influenzae biotype III. To our knowledge, this is the first reported case of meningitis caused by this biotype, which is not detectable by Hib antigen tests. PMID- 11758079 TI - Statin-associated myopathy. AB - Myopathy occurs in 0.1%-0.2% of patients receiving statins in clinical trials. This adverse effect is shared by all statins, but is more common with cerivastatin, especially in combination with gemfibrozil. The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions. Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available. PMID- 11758080 TI - Selecting participants for clinical trials. PMID- 11758081 TI - Is aggressive lipid-lowering therapy preferable to angioplasty in stable coronary artery disease? PMID- 11758082 TI - Role of breast magnetic resonance imaging in difficult diagnostic situations. AB - In some patients with breast disease, mammography and ultrasonography can provide only limited diagnostic information. Magnetic resonance imaging of the breast has high sensitivity and specificity and can play a significant diagnostic role in problem situations. Patients who are most likely to benefit are those with (i) axillary adenopathy of unknown primary origin, (ii) possible tumour recurrence after surgery or radiotherapy, (iii) lesions overlying implants, or (iv) those requiring staging of lobular or multifocal carcinoma. PMID- 11758083 TI - Appendicectomy--becoming a rare event. PMID- 11758084 TI - Comparison of Australian and US data on overweight and obesity in children and adolescents. PMID- 11758085 TI - Neuroleptic malignant syndrome: an underdiagnosed condition. PMID- 11758086 TI - Does cleansing the birth canal at delivery reduce postnatal infection rates? PMID- 11758087 TI - Hepatitis A epidemiology in Australia: national seroprevalence and notifications. PMID- 11758088 TI - Strongyloidiasis in veterans. PMID- 11758089 TI - Evidence-based obstetrics in Australia: can we put away the wooden spoon? PMID- 11758090 TI - [Which properties make a neuroleptic "atypical"?]. AB - The group of "atypical" neuroleptics is not a homogeneous class of drugs, but pharmacologically as well as clinically disparate. Furthermore, there seems to be a continuum between "conventional" and "atypical" neuroleptics. Based on preclinical findings with these drugs and their characteristics in SPECT- and PET studies, the most common concepts of neuroleptic "atypicality" are discussed. Combined D2-like dopamine/5-HT2-serotonin antagonism and preferential binding to mesolimbic dopamine neurons are believed to be the main pharmacological features of "atypical" compounds. For certain substances, affinities for specific neurotransmitter receptors as well as interactions with other non-dopaminergic systems may be essential. A relatively low affinity for D2-like dopamine receptors and binding to dopamine autoreceptors are probably of some importance for other compounds. The diversity of possible mechanisms suggests that there is not a single, pharmacologically established concept of "atypicality". A variety of biological mechanisms characterizes a heterogeneous group of substances, which also substantially differ in their clinical properties. PMID- 11758091 TI - [The startle reflex in schizophrenia research]. AB - Abnormalities of attention and information processing are described as important features of schizophrenia. Theoretically, they may reflect deficiencies in central mechanisms of inhibition and selection. These deficiencies are believed to lead to cognitive fragmentation in patients with schizophrenia. Findings of an impaired prepulse-inhibition (PPI) and habituation of the startle reflex in patients with schizophrenia are thought to represent preattentive, i.e., automatic attention deficits. Other paradigms with attentional instructions help to detect and to quantify deficits in controlled attentional functions. The PPI of the auditory startle blink reflex-mediated primarily by brainstem structures- is regulated by cortico-striato-pallido-pontine influences and by neurotransmitters involved in the pathogenesis of schizophrenia. An animal model of PPI provides the possibility to test neurobiological hypotheses in schizophrenia and to screen substances for their potential antipsychotic properties. Because reduction of PPI also occurs in other neuropsychiatric disorders, further studies are required to develop new paradigms of startle modification with findings of higher specificity and probable diagnostic relevance in patients with schizophrenia. PMID- 11758092 TI - [Development of a proverb test for assessment of concrete thinking problems in schizophrenic patients]. AB - Concretism is considered an important aspect of schizophrenic thought disorder. Traditionally it is measured using the method of proverb interpretation, in which metaphoric proverbs are presented with the request that the subject tell its meaning. Interpretations are recorded and scored on concretistic tendencies. However, this method has two problems: its reliability is doubtful and it is rather complicated to perform. In this paper, a new version of a multiple choice proverb test is presented which can solve these problems in a reliable and economic manner. Using the new test, it is has been shown that schizophrenic patients have greater deficits in proverb interpretation than depressive patients. PMID- 11758093 TI - [Schizophrenia and violence. Results of a comprehensive inquiry in an Austrian providence]. AB - The question as to whether schizophrenics have an increased potential for delinquency and violent behavior has given rise to much controversy. During the past few years, a large number of epidemiological studies have demonstrated a moderate but reliable relation between schizophrenic disorders and violence. In the present study, a new approach at investigation was used by evaluating the overall rate of convictions and commitments to psychiatric institutions for general delinquency, violence, and homicide among schizophrenics. The most outstanding results demonstrated that the treatment of schizophrenic offenders was only insufficiently covered by the psychiatric care system, showed the lack of compliance in the study group, and demonstrated the high significance of coexisting acute and chronic alcohol and drug abuse. The risk of delinquency and violent behavior was much higher in schizophrenics than in the general population. It is indicated, however, that mentally ill delinquents are only of minor importance within the overall group of offenders and that better preventive and therapeutic measures present opportunities for prevention. PMID- 11758094 TI - [Aggressive behavior in psychiatric patients. Possible modification by self defense training]. AB - We investigated the frequency, kind and intensity of aggressive behavior of 494 psychiatric patients at the time of admission. Nine to ten percent of this group showed aggressive behavior. Therefore since 1992 we have a self-defence training for the staff members with the intention of increasing the safety of staff members in situations of assault. Thirty-one staff members who participated in the self-defence training were given the opportunity to evaluate the program by means of self-rating scales. The results show that in their experience the training increases the extent of self-protective behavior and simultaneously decreases the amount of tension in assault-situations. In addition, we evaluated 18 assault-situations, that occurred during the last 2 years. We found out that 5 of 6 staff members who participated in the self-defence-training could protect themselves successfully in contrast to only 2 of 12 staff members who did not participate in this training. Eight of this group were injured during the assault. The results of our investigation indicate that the introduction of self defence training for staff members is helpful for the safety of staff members working in the field of psychiatry. PMID- 11758095 TI - [Interferon alpha-associated agranulocytosis during clozapine treatment. Case report and status of current knowledge]. AB - Little is known about possibilities of chronic hepatitis C treatment with interferon-alpha (IFN-alpha) in psychiatric patients continuously taking antipsychotics. We report on a 28-year-old hepatitis C-positive man with paranoid psychosis. He was successfully treated with clozapine, an atypical antipsychotic drug which is known for the risk of granulocytopenia and agranulocytosis. With doses up to 200 mg/day over 3 years, he showed no remarkable changes in WBC. Because of the chronic hepatitis C with genotype 3a, additional treatment was started with IFN-alpha (s.c., 3 x 6 million IU/week). After 2 months of therapy he developed a severe agranulocytosis. Both clozapine and IFN-alpha were discontinued, and his WBC returned to normal. Results from bone marrow examination were compatible with a toxic reaction possibly caused by either or both medications. We discuss possible problems with IFN-alpha during the treatment of psychiatric patients, interactions with psychiatric medication, and hematotoxic side effects like those from clozapine. We recommend combining IFN alpha with less "toxic" antipsychotics and weekly checks of WBC. PMID- 11758096 TI - [Olanzapine and pregnancy. 2 case reports]. AB - We report on two schizophrenic females who both had unexpected first pregnancies in their mid-thirties while being treated with olanzapine. Both patients had histories of psychosis of several years with some relapses and were treated previously with traditional antipsychotics. Since they wished to have children, no contraception had been performed past the age of 30. Both pregnancies occurred within a few months after the drug treatment was switched from traditional agents to olanzapine. Olanzapine was continued throughout the pregnancies, which were without complication. It is well known that treatment with traditional neuroleptics may lead to elevated prolactin levels and thus to relative infertility. Like clozapine, olanzapine has minimal effects on prolactin levels. These cases indicate that after switching from traditional neuroleptics to atypical agents, fertility may normalize and unplanned or even unwanted pregnancies may occur. Since olanzapine is widely prescribed, it is essential to inform women about the increased probability of pregnancy and the need of appropriate contraception. PMID- 11758097 TI - [Paranoia erotica (de Clerambault syndrome) in affective disorder]. AB - Erotomania is a rare delusional disorder usually associated with other psychic disorders, especially paranoid schizophrenia. The primary form without comorbidity is very rare. A case report is presented with characteristic features of the pure form of erotomania in a female patient that was nevertheless an affective disorder. A historical review is presented and the division of Clerambault's syndrome into primary and secondary categories critically discussed. PMID- 11758098 TI - [The psychologist and philosopher Wilhelm Wundt and a dedication by his student Emil Kraepelin]. PMID- 11758099 TI - [Wilhelm Griesinger (1817-1868)--his knowledge of psychiatry from the historical and current perspective]. AB - Thorough re-analysis of Wilhelm Griesinger's scientific work is very interesting not only from the historical point of view, but also with regard to the present day debate about the role and self-image of psychiatry. In the literature, Griesinger's ideas are often reported in a rather undifferentiated and condensed manner. Therefore, it may be overlooked that he did not avoid getting involved with the principal epistemological issues of psychiatry (which were an unpopular topic in his time as well), but discussed them intensively and with a constant look at their relevance for clinical and research purposes. PMID- 11758100 TI - [Reimbursement for psychiatric services in the new hospital DRG system. Response to the German Hospital Society (DKG)]. PMID- 11758101 TI - Surgical therapy in transsexual patients: a multi-disciplinary approach. AB - A transsexual patient has the constant and persistent conviction that he or she belongs to the opposite sex, thus creating a deeply seated gender identity conflict. With psychotherapy being unsuccessful, it has been proven that in carefully selected patients, gender reassignment or adjusting the body to the mind (both with hormones and surgery) is the best way to normalize their lives. Optimal treatment of these patients requires the multidisciplinary approach of a gender team with the input of several specialties. Such a team consists of a nucleus of physicians who sees the patient more frequently: the psychiatrist, the endocrinologist, the plastic surgeon, the gynecologist and the urologist and a more peripheral group that sees the patients more incidentally: the psychologist, the otorhinolaryngologist, the dermatologist, the speech therapist, the lawyer, the nurse and the social worker. Between 1987 and 1999, a total of 71 male-to female (MTF) and 54 female-to-male transsexuals have undergone gender confirming surgery in our hospital. This article gives a review and an update on the different surgical procedures as well as on the outcome in our patient population. The results in this series of patients clearly demonstrate that a close cooperation of the different surgical specialties, within our multidisciplinary gender team, is the key to success in treating transsexual patients. PMID- 11758102 TI - Endoscopic forehead lift. PMID- 11758103 TI - Experience with training in a foreign country. AB - Everyone is interested in going to a foreign country during or after trainingship. But going abroad will have an enormous impact on personal and professional life. We will reveal some tips and tricks about the USA, UK, France and The Netherlands. PMID- 11758104 TI - Live-donor liver transplantation: the USC experience. AB - BACKGROUND: Liver transplantation is currently the standard of care for patients with end stage liver disease. However due to the cadaveric organ shortage, live donor liver transplantation (LDLT), has been recently introduced as a potential solution. We analyzed and support our initial experience with this procedure at USC. MATERIAL AND METHODS: From September 1998 until July 2000, a total of 27 patients underwent LDLT at USC University Hospital and Los Angeles Children's Hospital. There were 12 children with the median age of 10 months (4-114) and 15 adults with the median age of 56 years (35-65). The most common indication for transplantation was biliary atresia for children and hepatitis C for adults. RESULTS: All donors did well postoperatively; the median postoperative stay was five days (5-7) for left lateral segmentectomy and seven days (4-12) for lobar donation. None of the donors required blood transfusion, re-operation or postoperative invasive procedure. However, five of them (18%) experienced minor complications. The survival rate in pediatric patients was 100% and only one graft was lost at nine months due to rejection. Two adult recipients died in the postoperative period, one from graft non-function and one from necrotizing fascitis. 37% of adult recipients experienced postoperative complications, mainly related to biliary reconstruction. Also 26% of the recipients underwent reoperation for some of these complications. CONCLUSION: LDLT is an excellent alternative to cadaveric transplantation with excellent results in the pediatric population. However, in adult patients it still carries a significant complication rate and it should be used with caution. PMID- 11758105 TI - Is needle biopsy of the liver necessary in staging laparotomy? AB - The purpose of this retrospective study was to examine the necessity of needle biopsy in staging laparotomy. Between 1988 and 1998, 31 patients diagnosed with Hodgkin's disease underwent staging laparotomy. All patients had lymph node sampling from perihilar, coeliac, periaortic and iliac regions, splenectomy, wedge biopsy of the liver as well as tru-cut needle biopsies from both liver lobes. Two patients (6.5%) had hepatic involvement of the liver detected by both wedge and needle biopsies. In the remaining patients, all biopsies of the liver obtained by either method were negative. These findings strongly suggest that wedge biopsy of the liver provides sufficient information for the diagnosis and there is no need for tru-cut biopsy which has its own complications. PMID- 11758106 TI - Emergency ventricular assist device: better survival rates in non-post cardiotomy related cardiogenic shock. AB - OBJECTIVE: The Abiomed BVS 5000 ventricular assist device (VAD) has been approved in Belgium for emergency cardiac support in patients with postcardiotomy failure with the aim of native heart function recovery. Other indications have emerged from world wide experience, but the indication and usefulness of emergency implantation of assist devices is often debated. METHODS: To decide which patients benefit most from emergency ventricular assist device implantation, we retrospectively reviewed our results of mechanical circulatory support with Abiomed in 20 patients over a 4-year period. Fifteen patients with mean age 58 +/ 6 years experienced postcardiotomy failure and underwent biventricular assist device (BVAD) implantation (group A), after elective (n = 9) or after emergency coronary artery bypass grafting (CABG) (n = 6). Five patients (group B), with mean age 35 +/- 19 years, had an implantation for other underlying conditions: hypertrophic cardiomyopathy (n = 3), myocarditis (n = 1) and primary cardiac allograft failure (n = 1). RESULTS: Of these two groups, eight and two patients respectively needed cardiopulmonary resuscitation before VAD implantation. The mean duration of support in both groups was 5.8 (range 12 h-13 days) and 4.4 days (range 2 h-9 days) respectively. Six and two patients could be weaned from the device and nine and one patients respectively, died on the device. Two patients in group B underwent successful heart transplantation and four patients in group A died after weaning. Two patients in the postcardiotomy group and four patients in group B survived (13% and 80%) with an overall survival and discharge rate of 30%. CONCLUSION: Although sample sizes are small, better survival rates with emergency Abiomed BVS 5000 implantation were obtained in the non postcardiotomy group (group B). For patients in the postcardiotomy group, outcome was negatively influenced by cardiac arrest and resuscitation before urgent CABG. Since death is the only alternative for these patients in cardiogenic shock and organ recovery cannot be predicted, we continue to consider emergency VAD implantation in this patient population. PMID- 11758107 TI - Arterial erosions in acute pancreatitis. AB - Acute pancreatitis was observed in 492 patients. Fourteen (2.8%) developed an arterial erosion revealed by a haemorrhage either in the digestive lumen, in the peritoneum or via previously placed drainage. The eroded artery was the splenic artery in six patients, a pancreatico-duodenal artery in five patients. An initial haemostasis was attempted by: a) embolization in four patients: one died; the three others had bleeding recurrence. b) splenocorporeal pancreatectomy in four patients, three had bleeding recurrence. c) arterial ligature in four patients: three had bleeding recurrence. Secondary haemostatic procedures were performed in ten patients but a durable haemostasis was achieved in only five patients: two had a pancreatic resection and three were treated by a redo binding. It is noteworthy that durable haemostasis could not be obtained neither by embolization nor by ligature in necrotic tissues. This could explain the difference in the results of arterial erosion treatments in chronic and in acute pancreatitis. Therefore, it is suggested that haemostatic procedures should be performed away from necrotic tissues, or eventually done after their removal. PMID- 11758108 TI - Urogenital tract trauma in Port Harcourt. AB - A retrospective study of urogenital tract injuries treated in the Urology Unit of Port Harcourt University Teaching Hospital from January 1985 to December 1994 was done. There were 67 injuries in 62 patients. Fifty-five (82%) of these were blunt injuries. Males were more frequently injured (85%) than females. Patients younger than 60 years sustained 61 of the 67 injuries (91%) with peak incidence in the age groups 0-10 years (22%) and 21-30 years (28%). The urethra was the most frequently injured structure (49%) followed by the bladder (24%). The anatomically secured kidney and ureter as well as the fairly mobile penis and scrotum were much less frequently injured. The commonest aetiological factor was road traffic accident (57%). There were ten injuries (15%) resulting from industrial activities. Eight injuries (12%) were iatrogenic. Treatment was successful in 52 injuries (78%). It was satisfactory in the few urethral injuries that required repeated dilations. Four injuries (6%) resulted in permanent disability. There were two deaths (2%) both from iatrogenic causes involving an ureteric injury at hysterectomy and haemorrhage from cultural circumcision in the village. Prevention is the most effective way to avoid these injuries. PMID- 11758109 TI - "What you see is not what you get". A plea to remove a 'normal' appendix during diagnostic laparoscopy. AB - BACKGROUND: Diagnostic laparoscopy (DL) is a well established alternative option to coeliotomy for suspected appendicitis. When a 'normal' appendix is found, appendectomy is often believe unnecessary. Little is known however about how normal a normal appearing appendix is. In this study we postulated that a normal appendix seen at DL, may show pathological indications at microscopy, and thus, to leave the appendix untouched may be unsafe. METHODS: A retrospective review of data from 48 patients which, in a five year period (1995-1999), had virtually normal appendices removed as completion of DL for lower abdominal pain. RESULTS: No procedure-related drawback and no subsequent complications were recorded. Symptoms subsided in all the patients. Mean hospital stay was 2.1 days. When receiving specimens, incidence of pathologic changes of the appendix were observed in 58 percent of the cases (n = 28). The negative predictive value of DL was 41 percent. CONCLUSIONS: Due to the consistently false negative rate of DL, and the low morbidity rate for laparoscopic appendectomy, we support incidental appendectomy in patients with lower abdominal pain. PMID- 11758110 TI - Transilluminated powered mini-phlebectomy: early clinical experience. AB - We report our preliminary experience with a new surgical endoscopic technique, the Transilluminated Powered Phlebectomy (TriVex System, Smith + Nephew) to remove varicose veins. TriVex System combined an irrigated illuminator device and a powered vein resector. There were 15 patients with a mean age of 50 years, nine were women and six were men. We evaluated prospectively the safety, efficacy and clinical benefits of this new surgical device. PMID- 11758111 TI - Endovascular treatment of an acute type B dissection: a case report. AB - The case of a young man with acute type B dissection is reported. Inserting an endovascular stentgraft was the treatment of choice, with a good short-term result. We do believe that this is a promising strategy in the management of this serious pathology in which the classical surgical treatment is still associated with an important mortality and morbidity. PMID- 11758112 TI - Thyroid carcinoma metastasis to the sternum: resection and reconstruction. AB - Metastases of thyroid carcinoma to the sternum are not so frequent and ablative surgery enables the patients to live longer with a better quality of life. After such a resection, the surgical defect has to be covered either by autogenous or artificial substitutes. We present a 62 years old patient with an asymptomatic sternal metastasis of a poorly differentiated follicular thyroid carcinoma. After radical excision, including the sternum, both clavicular heads and an upper mediastinal dissection, the defect was reconstructed in two layers, combining a Marlex mesh and a pedicled pectoralis major muscle flap. Postoperative course was uneventful and respiratory function was not disturbed. PMID- 11758113 TI - Pruritus. PMID- 11758114 TI - Graft-versus-host disease. PMID- 11758115 TI - Urticaria and angioedema. PMID- 11758116 TI - Development and morphogenesis of the skin. PMID- 11758117 TI - Mechanisms of T-cell homing to skin. AB - Although many individual components of the lymphocyte's migratory machinery have been identified and analyzed for function in vitro, interesting questions remain regarding the in vivo integration of these components. How does the lymphocyte "choose" a direction for migration in the complex cytokine/chemokine environment of inflamed dermis when multiple chemokines secreted by multiple cell types are present? Can differences in chemokine expression explain the clinical and histologic differences seen in different inflammatory skin disease? What are the roles of proteins such as VAP-1? Our present understanding of lymphocyte migration has already led to the use of monoclonal antibodies to integrins such as LFA-1 that can potentially be of therapeutic use in skin diseases such as psoriasis. Small molecule inhibitors of T lymphocyte-specific receptors such as CCR4 or CXCR3 are promising agents for controlling T cell-mediated inflammation but have yet to be developed. These receptors may have greater selective expression on skin-homing T cells and thus may decrease the risk of iatrogenic immunosuppression. Close cooperation between the pharmaceutical industry and basic scientists will hopefully lead to the evolution of such compounds and toward more effective treatment of inflammatory skin diseases. PMID- 11758118 TI - Connexin disorders of the skin. PMID- 11758120 TI - Pathogenesis of rosacea. PMID- 11758119 TI - Cutaneous angiosarcoma. PMID- 11758121 TI - New methods in cutaneous resurfacing. AB - The ongoing effort to create an optimal method of skin rejuvenation has led to several new treatment options. Microdermabrasion and various nonablative laser resurfacing systems produce minimal skin injury, whereas current RF resurfacing devices may create both ablative or nonablative effects. The less invasive methods do limit the length of an uncomfortable healing time; however, studies appear to indicate that the results are less impressive than those produced by more destructive techniques and may prove only temporary over the time frame of a year. Efficacy and durability of clinical improvement seem to be inversely related to the wounding depth, the length of the healing period, or both. The search continues for the perfect method of skin rejuvenation, which minimizes cost, healing time, adverse effects, and discomfort and maximizes efficacy, response durability, and reproducibility. With advancements in technology, rejuvenation methods slowly approach these elusive goals. PMID- 11758122 TI - Teledermatopathology. PMID- 11758123 TI - Cellular spindle cell proliferations of skin. PMID- 11758124 TI - Histopathology of the nail. AB - Patients are often very concerned about the diagnosis and treatment of an unsightly nail problem. Nail biopsy findings can enhance the accuracy of clinical diagnosis, just as skin biopsy is often crucial to the diagnosis of skin disease. In addition, nail biopsy may be necessary for the early detection of a malignant tumor. A skillfully performed adequate nail biopsy, handled and processed and interpreted properly, can be an important part of a dermatologist's armamentarium in providing excellent comprehensive patient care. PMID- 11758125 TI - Advances in digital imaging in dermatology. PMID- 11758126 TI - The cutaneous "histiocytoses". PMID- 11758127 TI - Non-polio enteroviruses in acute flaccid paralysis. AB - OBJECTIVE: Human enteroviruses are the major cause of aseptic meningitis and also cause a wide range of other acute illnesses, including neonatal sepsis like disease, meningitis, acute flaccid paralysis and acute hemorrhagic conjunctivitis. Infection in neonates is particularly life threatening. METHODS: Stool samples of 523 children (age < 4 years) showing symptoms of acute flaccid paralysis (AFP) were studied. National Polio Surveillance Project workers from different parts of Uttar Pradesh and Bihar collected the samples during June to October 1998. Non-polio enteroviruses (NPEV) were isolated in 191 cases only, by cell culture based neutralization assay. These NPEV isolates were further studied to find the frequent enterovirus serotype detected in stool of children having AFP. RESULTS: Data generated will help future studies on NPEV serotypes circulating in this area. CONCLUSION: In addition it may reduce unnecessary hospitalization, allow immune globulin batches of high titres to frequently circulating serotypes, to be reserved for intravenous therapy of neonates and guide the formulation of antigens for rapid and less expensive diagnosis. PMID- 11758128 TI - Pediatric sarcoidosis in India. AB - OBJECTIVE: Since 1957, when the first pediatric case of sarcoidosis was reported, 11 more cases have been traced in the Indian literature. METHODS: Nine of them were reported from general wards of hospitals (while the remaining 3 were from pediatric unit of AIIMS, New Delhi). Failure of initial treatment with anti tuberculosis drugs for some months, necessitated search for an alternative diagnosis. Considerable delay (several months to years) occurred due to several parent- or physician-dependant factors. RESULTS: Affection more in girls (9 to 12), universal fever and constitutional symptoms, loss of weight, scanty lung features, hepatomegaly, often with massive splenomegaly, frequent lymphadenopathy etc. caused initial confusion. CONCLUSION: Treatment with oral steroid or with chloquine and NSAIDS with or without steroid MDI gave equally good results. Long follow-up was done in a few cases only, showing relapses in nearly 66%. One case had a superinfection with acid-fast bacilli. PMID- 11758129 TI - An ergonomic study of chronic musculoskeletal pain in schoolchildren. AB - OBJECTIVE: Schoolchildren developing chronic musculoskeletal pain from carrying heavy backpacks (hereafter referred to as "pain") is a worldwide issue. The present study of two cohorts, consisting of 248 Indian and 103 American schoolchildren aged 9.0 to 20.6 years, using a semi-objective pain criteria, sought to answer the questions: Can pain be correlated with Body Mass Index (BMI), Weight Carried, Strength, Mood or Body Fat? What are the similarities and differences between the Indian and American schoolchildren in the above context? METHODS: After obtaining parental consent, the schoolchildren completed a questionnaire. Then, they were weighed with and without carry-on items and their height as recorded. Isometric arm and shoulder strengths were measured using the Jackson Strength Tester. Using a Skinfold Caliper, skinfold thicknesses at the right triceps and calf was measured. Using the Borg Pain Scale the students assessed the pain experienced from their own backpacks, rated the acute pain experienced while carrying a standard 10 kg. or 7 kg. backpack. RESULT: Half the schoolchildren reported pain located primarily in the shoulders and back (where most students carry their backpacks). Pain did not correlate with study variables (p > 0.05), and the student moods were mostly happy or neutral. Americans are five times as stressed or sad than the Indians, and the average weight carried decreased as the grade increased. The mean of the age, height, arm and shoulder strengths, and BMI for the 5th to 8th grade schoolchildren (younger groups) and the 9th to 12th grade schoolchildren (older groups), in India, was lower than their American counterparts (p < 0.05). In contrast, the weight carried to school by the Indian children was higher (p < 0.05). The mean pain level perceived by both the younger and older groups in both countries, was not statistically different (p > 0.05). CONCLUSION: Musculoskeletal pain in schoolchildren due to carrying heavy backpacks is a significant problem. There are some similarities, but a number of differences between the Indian and American schoolchildren. Implementing the Pain Prevention Screening is expected to minimize pain, if not lead to a pain-free child. PMID- 11758130 TI - Serum cardiac troponin-I in active rheumatic carditis. AB - OBJECTIVE: The study was performed to investigate the level of serum cardiac troponin I (cTnI), a specific marker for myocardial cell damage, in the acute rheumatic carditis (RC). METHODS: Twenty seven consecutive patients with acute RC and 23 healthy children were enrolled. RESULT: cTnI level in both groups showed no statistical difference (p > 0.05). CONCLUSION: Serum cTnI level did not gain clinical use. PMID- 11758131 TI - Lower arrythmogenic risk of low dose albuterol plus ipratropium. AB - OBJECTIVE: Wheezy infants are in need of urgent bronchodilatation owing to their intermittent bronchoconstriction. beta 2 agonists are frequently used in emergencies and have previously shown to increase the QT dispersion (QTd), which may be associate with high risk of cardiac arrhythmia, in asthmatics. However, effect of low dose beta 2 agonist therapy in combination with the anticholinergic agents on QTd in wheezy infants is not known. This study aimed to assess the effect of standard dose of nebulized albuterol (NAB) and low doses of NAB combined with ipratropium-bromide (NIB) on QTd in wheezy infants. METHODS: Twenty nine children, under 2 years old, with the diagnosis of wheezy infant with acute exacerbation were enrolled in the study. Thirteen were treated by standard dose of NA therapy (0.15 mg/kg) and low doses of NAB (0.075 mg/kg) plus NIB (250 micrograms/dose) therapy was given to the remaining subjects. Respiratory distress score, O2 saturation and side effects were studied and QTd were measured from the standard electrocardiograms at baseline and after treatment. Significant improvement was achieved in clinical score and oxygenation of both groups. RESULT: The evaluation of the corrected QTd (QTcd) showed that there was no significant difference between pretreatment values of both groups (p > 0.05). However, while there was no statistically significant difference in the pre and post-treatment values of QTcd of infants treated with combination therapy, QTcd was found to be significantly increased in NAB group after treatment (p < 0.05). CONCLUSION: Our results suggest that, while clinical improvement is same, the increase of the QT dispersion is more prominent with the use of standard dose of NAB compared to low dose NAB plus NIB therapy. So, low dose of beta 2 agonist in combination with anticholinergic agents may much safer than the use of standard dose of beta 2 agonists alone in regard to preventing the possibility of arrythmogenic effects in wheezy infants with acute exacerbation. PMID- 11758133 TI - Apnea in the newborn. AB - Apnea, defined as cessation of breathing resulting in pathological changes in heart rate and oxygen saturation, is a common occurrence in sick neonates. Apnea is a common manifestation of various etiologies in sick neonates. In preterm children it may be related to the immaturity of the central nervous system. Secondary causes of apnea should be excluded before a diagnosis of apnea of prematurity is made. Methylaxanthines and Continuous Positive Airway Pressure form the mainstay of treatment of apnea in neonates. Mechanical ventilation is reserved for apnea resistant to above therapy. An approach to the management of apnea in neonates has been described. PMID- 11758134 TI - Hypoglycemia in the newborn. AB - Since a universal definition for hypoglycemia is lacking, an operational threshold for initiating therapy has been defined. Hypoglycemia is encountered in a variety of neonatal conditions including prematurity, growth retardation and maternal diabetes. Since hypoglycemia may be asymptomatic, routine screening for this condition in certain high risk situations is recommended. Supervised breast feeding may be a treatment option in asymptomatic hypoglycemia. However, symptomatic hypoglycemia should always be treated with a continuous infusion of parenteral dextrose. Neonates needing dextrose infusion rates above 12 mg/kg/m should be investigated for refractory causes of hypoglycemia. Hypoglycemia has been linked to poor neuro-developmental outcome and hence aggressive screening and treatment is recommended. PMID- 11758132 TI - Transfusion transmitted diseases. AB - Transfusion transmitted disease (TTD) is a major challenge to the transfusion services all over the world. The problem of TTD is directly proportionate to the prevalence of the infection in the blood donor community. In India, hepatitis B/C, HIV, malaria, syphilis, cytomegalo virus, parvo-virus B-19 and bacterial infections are important causes of concern. Hepatitis B and C infections are prevalent in India and carrier rate is about 1-5% and 1%, respectively. Post transfusion hepatitis B/C is a major problem in India (about 10%) because of low viraemia and mutant strain undetectable by routine ELISA. HIV prevalence among blood donors is different in various parts of the country. It may not be so alarming as projected by some agencies. In one study from north India, confirmed HIV positivity was found in 0.2/1000 blood donor. Post transfusion CMV is difficult to prevent but use of leukocyte filters may help to reduce it significantly. Parvo virus B-19 infection in blood donors is 39.9% which may increase morbidity in multitransfused or immunocompromised patients. Current symphilis tests may not be sensitive but it should be continued to exclude high risk donors. Malaria is a real problem for India due to the lack of a simple and sensitive screening test. Incidence of bacterial contamination is greatly reduced due to improved collection/preservation techniques and use of antibiotics in patients. However, proper vigilance and quality control is needed to prevent this problem. Total dependence of altruistic repeat voluntary donors and use of sensitive laboratory tests may help Indian blood transfusion services to reduce incidences of TTDs. PMID- 11758135 TI - Seizures in the newborn. AB - Seizures in the newborn period constitute a medical emergency. Subtle seizures are mild paroxysmal alterations in motor or autonomic activity and are unique to the neonatal period. They are likely to be missed or confused with benign movements observed commonly in preterm children. Focal clonic seizures have a better prognosis as compared to myoclonic seizures for long-term neuro developmental outcome. Seizures due to sub-arachnoid hemorrhage and late onset hypocalcemia carry a better prognosis as compared to seizures due to hypoglycemia, meningitis and cerebral malformations. Hypoglycemia and hypocalcemia are common causes and should be excluded in all neonates with seizures. Multiple etiologies can co-exist in neonatal seizures and a comprehensive approach for management of neonatal seizures has been described. PMID- 11758136 TI - Hypocalcemia in the newborn. AB - Healthy term babies undergo a physiological nadir in serum calcium levels by 24 48 hours of age. This nadir may be related to the delayed response of parathyroid and calcitonin hormones in a newborn. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. This early onset hypocalcemia which presents within 72 hours, requires treatment with calcium supplementation for at least 72 hours. In contrast late onset hypocalcemia usually presents after 7 days and requires long term therapy. Ionized calcium is crucial for many biochemical processes and total serum calcium is a poor substitute for the diagnosis of hypocalcemia. PMID- 11758137 TI - Jaundice in the newborn. AB - Hyperbilirubinemia is the commonest morbidity in the neonatal period and 5-10% of all newborns require intervention for pathological jaundice. Neonates on exclusive breast-feeding have a different pattern of physiological jaundice as compared to artificially fed babies. Guidelines from American Academy of Pediatrics (AAP) for management of jaundice in a normal term newborn have been included in the protocol. Separate guidelines have been provided for the management of jaundice in sick term babies, preterm and low birth weight babies, for jaundice secondary to hemolysis and for prolonged hyperbilirubinemia. Although hour specific bilirubin charts are available, these have to be validated in Indian infants before they are accepted for widespread use. PMID- 11758138 TI - Patent ductus arteriosus in preterm neonates. AB - Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3-4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease. PMID- 11758139 TI - Prevalence of beta hemolytic streptococci carrier rate among schoolchildren in Salem. AB - A preliminary study was conducted to identify the carriers of beta hemolytic streptococci (BHS) among school children. BHS were identified, grouped by latex agglutination test and tested for susceptibility to penicillin, erythromycin and cefazolin from their throat swabs. Prevalence of BHS was found to be 21.6% with group G (43.2%) as the predominant group followed by group A (28.8%). All the isolates were sensitive to the antibiotics tested. Health cards were issued to the carriers of group A beta hemolytic streptococci. PMID- 11758140 TI - Kawasaki disease. AB - Kawasaki disease (KD) is a systemic necrotizing vasculitis affecting medium and small sized arteries. The diagnosis is based entirely on recognition of a typical sequence of clinical features. Detection of any one clinical feature does not have any diagnostic significance. We report an uncommon case of Kawasaki disease in 10 months old male child with the analysis of its natural history, etiopathology, treatment and prognosis of the disease. PMID- 11758141 TI - Fatal cardiac malformation in fetal valproate syndrome. AB - A neonate with a fatal cardiac malformation due to maternal valproate intake during pregnancy is presented. PMID- 11758142 TI - Regression of attained milestones in an HIV infected infant. AB - We report a case of an 18-month-old child with regression of attained developmental milestones as a manifestation of HIV encephalopathy. This is the first such report in Indian literature. Commencing antiretroviral therapy in this child resulted in arrest of further regression of milestones. This alerts pediatricians to be aware that early developmental delay and regression may be a presenting manifestation of HIV infection in a child. PMID- 11758143 TI - Hemophagocytic lymphohistiocytosis (HLH) presenting on the 3rd day of life. AB - Hemophagocytic lymphohistiocytosis (HLH) embraces the frequently indistinguishable conditions, namely familial hemophagocytic lymphohistiocytosis (FHLH), sporadic hemophagocytic lymphohistiocytosis (SHLH) and virus associated hemophagocytic syndrome (VAHS). The disease is very rare and invariably lethal. Evidence suggests that the disease may be due to an inherited defect in immunoregulation that predisposes to an uncontrolled proliferation of activated histiocytes in response to a stimulus such as viral infection. We report here a 3 day-old neonate with confirmed HLH who had a stormy course and a fatal outcome to the disease process, in spite of early chemotherapy. To our knowledge, we believe this is the youngest reported case of HLH from Middle East. No familial or infective cause could be attributed. PMID- 11758144 TI - National health: time for occupational health. PMID- 11758145 TI - Sleep related vehicle accidents on Italian highways. AB - Sleepiness has been identified as a significant risk factor for vehicle accidents, and specific surveys are needed for Italy. The aim of this study was to assess incidence and characteristics of sleep-related vehicle-crashes on Italian highways. The database of the Italian National Institute of Statistics (1993-1997) was the source for the survey (50859 accidents with 1632 (3.2%) ascribed to sleep by the police). The distribution of accidents was evaluated by means of the analysis of variance considering the year, the day of the week, the age and the time of day and their interactions as main factors. The relative risk of sleep-related accidents was also evaluated with reference to the relative traffic density as estimated by the Italian Highways Society. The counts of sleep related accidents, and even more the relative risk, revealed the presence of peaks and troughs in zones at a higher level of sleepiness and alertness respectively. Death of the driver occurred in 11.4% of sleep related accidents versus 5.6% in general accidents. The great majority of sleep-related accidents occurred to drivers under 35 (61.4%) mainly during the night with an increasing trend in the yearly number of sleep-related accidents, especially on weekends. Therefore sleepiness appears a remarkable risk factor and, in our opinion, its incidence as sole or contributory cause of accidents on Italian highways is still underestimated. PMID- 11758146 TI - 153Sm-EDTMP radionuclide treatment of bony metastatic disease: a radiation protection evaluation. AB - The aims of the study were the identification and optimization of the radiation protection measures for in-patients who underwent palliative radionuclide therapy for bone metastases with 153Sm-EDTMP activities lower than 3 GBq. The suitability of the preventive procedures from the contamination of places and objects, and for the protection of the hospital staff, other patients and relatives from the danger of external radiation and internal contamination has been evaluated by carrying out a series of measurements both of superficial contamination inside the confinement room and of the dose near the treated patients. The results show that the contamination of the places and the objects close to treated patients is really low. The greatest risk of contamination depended on the management of the physiological waste that, therefore, should be collected and disposed as radioactive one. The measurements of external radiation show that nearby the confinement room the dose limit for public is not exceeded. The same is true for the dose limit of 3 mSv established for relatives who, when taking care treated patients, receive a dose lower than 20 microSv a patient. The fulfillment of the proposed radiation protection measures assures the containment of the risk of exposure and contamination for nursing and medical staff involved in radionuclide based therapy. PMID- 11758147 TI - [Anxiety, life style and obstetric history of women working in a high-fashion clothing industry]. AB - Women with a mean age of 38 years (range 20-62) were employed in an industry producing clothes of high fashion. A part of them (n = 210) performed their activities with hands and others (n = 90) utilising machines with more repetitive procedures. All the recruited women answered to a questionnaire including the state-trait anxiety inventory (STAI) test, working activities, lifestyle and obstetric history. There was no relation between obstetric history and working activities. The group of women with age ranging from 35 to 42 years showed the score of the STAI higher than that of the younger women and slightly lower than that of the subjects with older age. This may depend on the "healthy worker effect" in the old subjects able to continue their job. The scores of the STAI were also slightly influenced by the repetitive tasks utilising machines. On the whole, the working activity of women had beneficial effect on their role inside the family and in the social life. PMID- 11758148 TI - [Guidelines for the prevention of allergic reactions to latex in patients and health personnel]. PMID- 11758150 TI - [Protection from cancerogenic and mutagenic agents in the light of the legislative decree n. 66 of February 22, 2000]. AB - This publication provides an updating on Italian legislation regarding occupational carcinogen and mutagen agents. A Law Decree (chapter VII of law 626/94), deals specifically with carcinogen agents and provides a series of mandatory measures under the responsibility of a specific company preventive task aimed towards risk reduction or its complete elimination. The exposure estimation is essential both for future prevention activities as well as for the efficacy evaluation of measures that have already been carried out. The 626/94 Decree amendment (see Decree 66 of 25/2/2000), is a consequence of the EU Directive acknowledgement by Italy, on the protection of workers from risks related to carcinogens/mutagens exposure during work time. These amendments regard both definition parameters such as carcinogens/mutagens, as well as occupational exposure limits introduction for some of these agents i.e. benzene, VCM and wood dusts. PMID- 11758149 TI - [Retrospective study on the prevalence of latex allergic pathology in health personnel]. AB - To evaluate the prevalence of latex sensitisation and latex-related symptoms, we performed a study on 837 hospital employees. All subjects were asked for medical and occupational history, and underwent Skin Prick Test (SPT) with latex and other airborne allergens. The results showed a prevalence of latex sensitisation of 6.1% and a prevalence of symptoms of 5.26%. The most frequent symptoms were oculorhinitis, dermatitis and asthma. The one-year retrospective evaluation showed, in a group of 767 hospital attendants selected by the whole population, an incidence of sensitisation of 0.26%; no new cases of latex-related symptomatology were observed. The improvement of symptoms was due to the reduction of the exposure to latex gloves. The results of the study confirm the importance of prevention strategies. PMID- 11758151 TI - [High-pressure liquid chromatography (HPLC) with UV developer for the analysis of N-acetyl-S-(N-methylcarbomoyl)cysteine (AMCC)]. AB - N,N-dimethylformamide (DMF) is a solvent widely used to prepare synthetic fibers. Biomonitoring of DMF is usually performed by measuring urinary N-methylformamide, which allows us to estimate exposure during the working day. An alternative biomarker is the mercapturic acid N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) whose excretion accounts for about 13% of the absorbed DMF dose. Owing to its slow excretion (mean half-life = 23 hours) the urinary levels of AMCC at the end of a workweek reflect the cumulative dose of DMF during the whole week. Methods given in literature for measuring AMCC need the derivatization of the molecule before analysis. The paper describes a method for the determination of urinary AMCC by high-performance liquid chromatography (HPLC) with direct UV detection. Samples were purified by solid phase extraction with C18 and ENV+ cartridges, then 10 microliters were directly injected onto an Aminex HPX-87H Ion Exclusion column maintained at a temperature of 37 degrees C. Analyses were performed by isocratic run with 1 mM sulphuric acid delivered at 0.85 mL/min. The detector was set at 196 nm. Under these conditions, AMCC eluted at 11.1 min., and the detection and quantification limits were 1.32 mg/L and 3.96 mg/L, respectively. The performance of the method was evaluated on samples containing 25 mg/L and 400 mg/L of AMCC: each sample was analysed three times. The mean recovery of the extraction procedure was 88.3%. The precision (CV%) and the accuracy (Error%) ranged from 0.8% to 2.9%, and from -1.2% to +3.2%. The calibration curve was linear up to a concentration of 1000 mg/L, the coefficient of correlation was r = 0.9997. AMCC was measured in urine samples from 30 exposed and 20 unexposed (smokers and nonsmokers) subjects. Measurable amounts of AMCC were found in all of the samples from workers exposed to DMF; on the contrary, none of the samples from unexposed subjects contained this metabolite. The proposed method is sufficiently sensitive and specific for the evaluation of occupational exposure to DMF, thus it could be useful for the biological monitoring of workers exposed to this solvent. PMID- 11758152 TI - [Evaluation of the risk related to repetitive work activities: testing of several methods proposed in the literature]. AB - Pathologies due to the repetitive activity of the upper limbs constitutes a growing part of the work-related musculo-skeletal disorders. At the moment, there are no universally accepted and validated methods for the description and assessment of the work-related risks. Yet, the criteria fundamentally characterizing the exposure are rather clear and even. This study reports a practical example of the application of some recent risk assessment methods proposed in the literature, combining objective and subjective measures obtained on the field, with the traditional activity analysis. PMID- 11758153 TI - [Sickness Impact Profile: the Italian version]. AB - The Sickness Impact Profile (SIP) is one of the questionnaires most widely used for the generic evaluation of functional health status. Besides measuring functional status or quality of life, it is also a precious font of information for the psychologist in the inpatient-rehabilitative context when planning an intervention focused on the most dysfunctional areas indicated by the subject. In producing the Italian version of the SIP, attention was duly paid in the translation to maintain equivalence in terms of idioms, grammar and syntax, so as to render it free of erroneous translations or possible. misunderstandings. Since the SIP employs "weighted" items, in order to obtain the weights corresponding to each individual statement a 3-phase procedure was followed: A) each subject "judge" was asked to express on a scale his/her own dysfunctionality judgement for each item; B) statements with the highest and lowest mean weight for each category were identified; C) the same "judges" were then asked to reclassify the statements which had obtained the highest and lowest weights, respectively, on a scale of 15 equidistant intervals; subsequently the same subjects completed the SIP a second time (retest). Results show that the judges were coherent in their estimation of the specific weights for each item. In the judges' second completion of the SIP it was found that the majority of the test-retest correlations fell almost always within the r = 0.70-0.90 range. Moreover, given the marginal difference between Italian and United States weights, both methods may be used for the calculation of the scores. One thus concludes that the SIP questionnaire can be applied in the Italian context. PMID- 11758154 TI - [Neuropathic pain syndromes: from their diagnosis to the return to work. Proposal of a model for rapid evaluation and therapy based on their pathogenic mechanisms]. AB - The therapeutic approach to neuropathic pain differs significantly among physicians. This is in large part because of the relative paucity of randomized clinical trials and the scarcity of comparative studies with different drugs. Clinical studies on the efficacy of a drug or a technique are generally referred to the pathologic diagnosis and not to the pain mechanism. We have learned from animal models the different pain mechanisms which may be involved in the peripheral nerves and the spinal cord. Unfortunately, one mechanism could be responsible for many different symptoms, while the same symptom can be caused by different mechanisms. The authors propose a simple model to evaluate the patients in order to define the mechanisms involved an to select the treatment strategy. The diagnostic model allows classification of the patient into four groups according to pain mechanism (spinal neurons sensitization due to deafferentation, ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to nociceptors sensitization). The authors propose also a second step in which a fifth mechanism, adrenosensitivity, is evaluated. Treatment options may target any of the mechanisms discussed. Drugs and analgesic techniques can be classified according to their action on pain mechanisms. The authors identify in the literature some drugs and techniques which can be tested in each defined groups. A complementary and multidisciplinary rehabilitative approach of chronic pain patients is recommended. PMID- 11758155 TI - Undergraduate osteopathic medical education. PMID- 11758156 TI - Osteopathic graduate medical education. PMID- 11758157 TI - Certification of osteopathic physicians. PMID- 11758158 TI - AOA continuing medical education. PMID- 11758159 TI - Osteopathic postdoctoral training institutions. PMID- 11758160 TI - Accreditation at colleges of osteopathic medicine. PMID- 11758161 TI - The Osteopathic Graduate Medical Education Development Initiative. PMID- 11758162 TI - [Psychophysiological diseases--new challenge in the 21th century]. PMID- 11758163 TI - [Latent adenovirus infection in chronic obstructive pulmonary disease]. AB - OBJECTIVE: To study latent adenovirus infection in the stable stage of chronic obstructive pulmonary disease(COPD). METHOD: The bronchial epithelial cells and alveolar macrophages from 12 patients with chronic bronchitis, 10 patients with COPD, 6 patients with asthma and 8 healthy volunteers were obtained by bronchosocpy. The adenoviral DNA was determined in the epithelial cells and macrophages. All patients were in the stable stage. The polymerase chain reaction(PCR) was used for detection of the adenoviral genome E1A. RESULTS: The E1A region of adenovirus was found in the epithelial cells of COPD and chronic bronchitis patients (27%), not found in the patients with asthma and normal volunteers. Furthermore, E1A DNA was much more commonly in the COPD patients (50%) than in the patients with chronic bronchitis (8%) (P < 0.05). CONCLUSIONS: Latent adenoviral infection was present in the stable stage of COPD and may be related to the pathogenesis of the disease. PMID- 11758164 TI - [The changes of Clara cell in the distal conducting airways of patients with COPD]. AB - OBJECTIVE: To investigate the role of Clara cells in the pathogenesis of COPD. METHODS: Lung samples of pneumonectomy were collected from 13 patients with COPD and 13 patients without COPD. They had similar age, sex and smoke index. The number and distribution of Clara cells were measured by immunohistochemistry. The mRNA expression and protein level of CC16 were determined by riboneuclease protection assay and Western blot separately. RESULT: The number of Clara cells of the respiratory brochioli was lower in patients with COPD than in those without COPD (16.4% vs. 18.5%, P < 0.05). The expression of CC16 mRNA was also lower in patients with COPD than those without COPD(0.28 +/- 0.05 vs. 0.45 +/- 0.05, P < 0.05). There was no obvious difference of CC16 protein level between these two groups. CONCLUSION: The changes of the number and function of Clara cell may be one of the factors in the development of COPD. PMID- 11758165 TI - [mRNA expression of matrix metalloproteinase-2 and membrane type matrix metalloproteinase in pulmonary fibroblasts and macrophages of rat pulmonary fibrosis model]. AB - OBJECTIVE: To study the changes and significance of MMP-2 and MT1-MMP mRNA expressions in fibroblasts and macrophages of rat pulmonary fibrosis model. METHODS: Fifty pathogen-free Sprague-Dawley rats were randomly divided into ten groups. Five groups were instillated with bleomycin A5 (BLM A5) intratracheally, while 5 control groups with normal saline instead. Pulmonary interstitial fibroblasts and alveolar macrophages were isolated at day 1,3,7,14,28th after BLM exposure. The mRNA expression of MMP-2 and MT1-MMP was evaluated by RT-PCR quantitative analysis. RESULTS: (1) The MMP-2 gene expression of fibroblasts increased 2.05 times(t = 10.667, P < 0.01) higher than that of control in 24 hours after bleomycin instillation and remained at the high level until the 28th day after exposure. It was only slightly increased in macrophages at the first day (t = 3.27, P < 0.05) and dropped down to the level of control during pulmonary fibrosis. (2) The mRNA expressions of MT1-MMP were enhanced both in fibroblasts and macrophages of fibrosis groups. They were 2.1 times(t = 4.823, P < 0.01) higher than that of control at the 14th day and 1.8 times(t = 4.016, P < 0.01) at the 28th day, respectively, in fibroblasts, while it was 2.4 times(t = 5.851, P < 0.01) higher than that of control at the 28th day in macrophages. CONCLUSIONS: (1) Fibroblasts not only were the target cells but also involved in the damage of the pulmonary basement membrane and in the initiation of pulmonary fibrosis mediated by up-regulation of the mRNA expression of MMP-2. (2) The highly expressed MT1-MMP of fibroblasts and macrophages in the late stage of pulmonary fibrosis participated in the activation of pro-MMP-2 to promote the progression of pulmonary fibrosis. PMID- 11758166 TI - [Chronic hypoxia altered the mRNA expression of cyclooxygenase in intrapulmonary artery smooth muscle cell]. AB - OBJECTIVE: To elucidate the effect of chronic hypoxia on the cyclooxygenase-2 mRNA expression in pulmonary artery smooth muscle cells of rats. METHODS: The gene expressions of COX-1 and COX-2 during acute hypoxia were measured with semi quantified RT-PCR in the 2nd, 4th and 6th subculture of intrapulmonary artery smooth muscle cells (PASMC) of wistar rats under normoxic and continuous hypoxic condition separately. RESULTS: In all three generations, the expressions of COX-1 had no significant changes in hypoxia, while the COX-2 mRNA expression was higher in chronic hypoxic group than that in normoxic group and elevated with the duration of hypoxia exposure. After exposure to acute hypoxia, the augmentation of COX-2 mRNA expression in PASMC was higher in chronic hypoxic group than in normoxic group in all three subcultures. CONCLUSION: Chronic hypoxia could enhance the mRNA expression of cyclooxygenase-2 caused by acute hypoxia in PASMC of rats. It might be responsible for the lower HPV under chronic hypoxia. PMID- 11758167 TI - [Influence of suppressor gene p16 on retinoic acid inducing lung cancer cell A549 differentiation]. AB - OBJECTIVE: To investigate the role of suppressor gene p16 in the process of differential regulation of retinoic acid (RA) on the A549 lung cancer cells. METHODS: Tumor suppressor gene p16 was transfered into A549 cells and the cells were treated with all-trans retinoic acid (ATRA) at the dosage of 5 x 10(-6) mol/L for 4 d. After that, the proliferation and differentiation of A549 cells were examined by growth curve and cytometry analysis, the change of lung lineage specific marker MUC1 was tested by immunohistochemical staining. Meanwhile, Western blot was used to observe the change of p16 protein expression in A549 cells treated with ATRA. RESULTS: ATRA could obviously inhibit the growth and induce the differentiation of A549 cells that were transfered with p16 gene. There were more cells arrested in G1/G0 phase and the expression of MUC1 was markedly down-regulated than in control cells. The expression of p16 protein was up-regulated in A549 cells treated with ATRA. CONCLUSION: Suppressor gene p16 could enhance the effects of RA on proliferative suppression and differential induction of A549 cells. PMID- 11758168 TI - [A study on beta-lactamase activity of biofilm Escherichia coli]. AB - OBJECTIVE: To investigate the mechanism of drug resistance of biofilm escherichia coli. METHODS: The model of escherichia coli biofilm was established with the flat-board method. And the biofilm was confirmed by scanning electron microscopy. The beta-lactamase activities were quantitated, in escherichia coli, biofilm escherichia coli, biofilm escherichia coli induced by impenem or cefoxitin. RESULTS: The beta-lactamase activity of biofilm escherichia coli was 2.16 times as much as that of escherichia coli planctonically, and the beta-lactamase activities of biofilm escherichia coli induceded by impenem or cefoxitin were 1.30 and 1.05 times as much as those of biofilm escherichia coli, respectively. CONCLUSION: The drug resistance to antibiotics of biofilm escherichia coli was related to the production of beta-lactamase. PMID- 11758169 TI - [Changes of Ca2+ channel behaviors in bronchial smooth muscle cells of asthma guinea-pig model]. AB - OBJECTIVE: To investigate the relationship between the change of calcium channel behavior in bronchial smooth muscle cells (BSMCs) and the airway hyperresponsiveness in guinea-pigs with asthma. METHODS: The changes of calcium channel dynamics in BSMCs of 4 asthma guinea-pig models (22 cells) and 5 normal guinea-pigs (25 cells), and the inner peak calcium current in BSMCs of 5 asthma guinea-pig models (25 cells) and 6 normal guinea-pigs (24 cells) were determined by patch-clamp techniques. RESULTS: (1) The open time of calcium channel in BSMCs of asthma group was (1.70 +/- 0.40) ms, 2.32 times as much as that of control group (0.70 +/- 0.10) ms; the close time of calcium channel in BSMCs of asthma group (5.7 +/- 0.6) ms, was significantly shorter that that of control group (7.9 +/- 0.4) ms; The open probability in asthma group (0.40 +/- 0.10)% was significantly increased than that of control group (0.20 +/- 0.20)%, (P < 0.01); (2) The inner peak calcium current in BSMCs of asthma group was (-54 +/- 23) PA, 1.17 times as muth as that of control group (-25 +/- 8) PA, (P < 0.01). CONCLUSION: The enhanced activity of calcium channel an BSMCs of asthma guinea pig mudels may be one of the important factors responsible for the airway hyperresponsiveness. PMID- 11758170 TI - [The influence of dexamethasone on mRNA expression of interleukin-5, interleukin 3 and granulocyte-macrophage colony-stimulating factor receptors in eosinophils of guinea pig asthma model]. AB - OBJECTIVE: To investigate the iufluence of dexamethasone (DM) on expression of interleukin-5 receptor alpha(IL-5R alpha), interleukin-3 receptor alpha (IL-3R alpha), granulocyte-macrophage-colony-stimulating factor receptor alpha(GM-CSFR alpha) and common beta receptor (beta cR) in bronchalveolar lavage fluid (BALF) eosinophils in guinea pig asthma model, and to study the mechanism of promotion effect of steroid on eosinophil apoptosis. METHODS: 18 guinea pigs were divided into three groups randomly, normal control group, asthma group and DM-treated group. Asthma models of guinea pig were sensitized by ovalbumin(OVA). Hypodense EOS (HEOS) and normodense EOS (NEOS) were purified from BALF by gradients of percoll. Apoptosis was detected by method of TdT-mediated dUTP nick end labeling. The mRNA expression of IL-5R alpha, IL-3R alpha, GM-CSFR alpha and common beta receptor (beta cR) in eosinophils were measured by RT-PCR and in situ hybridization. RESULTS: Apoptosis of HEOS and NEOS in asthma group(4.0 +/- 2.0 and 3.0 +/- 2.0, respectively) were significanteylower than normal group(8.0 +/- 2.0 and, 7.0 +/- 2.0 respectively, P < 0.01), while the numbers of EOS cells (75.2 +/- 12.6 and 50.7 +/- 11.2, respectively) were significantly higher than normal group (4.8 +/- 1.5 and 9.5 +/- 2.6, respectively, P < 0.01). The BALF HEOS and NEOS of asthma group were remarkably reduced after DM treatment (14.8 +/- 8.0 and 20.0 +/- 7.0, respectively, P < 0.01), Eosinophils apoptosis in DM-treated group (24.0 +/- 5.0 and 22.0 +/- 4.0, respectively) was remarkably higher than those in asthma group (P < 0.01); The expressions of IL-5R alpha, IL-3R alpha, GM CSFR alpha mRNA of BALF EOS of asthma group were significantly lower, but the expression of beta cR mRNA was significantly higher than those of normal group(P < 0.01, 0.05). The expressions of IL-5R alpha, IL-3R alpha, GM-CSFR alpha mRNA in EOS of DM-treated group were significantly higher, while the expression of beta cR mRNA were significantly lower than those of asthma group (P < 0.01, 0.05). CONCLUSIONS: DM promote the apoptosis of BALF EOS of guinea pigs asthma models. and reduce EOS infiltration in lung of guinea pigs asthma models. It also decreased the effect of IL-5, IL-3 and GM-CSF and promoted the apoptosis of lung EOS through inducing the mRNA expression of their specific alpha chain and reducing the mRNA expression of the common beta chain. PMID- 11758171 TI - [Construction and immunogenicity of DNA vaccine encoding secreted form of Ag85B protein of Mycobacterium tuberculosis]. AB - OBJECTIVE: To construct the recombinant eukaryotic plasmid DNA expression vector encoding Mycobacterium tuberculosis antigen 85B (Ag85B) and to investigate its immunogenicity. METHODS: The gene encoding secreted form of Ag85B was amplified by polymerase chain reaction (PCR) from genome of Mycobacterium tuberculosis H37Ra strain, and was inserted into sites cut with Hind III plus EcoR I of eukaryotic expression vector pcDNA3 after restriction endonuclease digestion. The gene fragment encoding secreted form of Ag85B was inserted into the vector of E. coli JM109 strain and was confirmed by restriction endonuclease digestion. After 4 weeks since BALB/c mice were vaccinated by recombinant eukaryotic expressing vector, dot blotting and ELISA were used to detect the serum antibody against Ag85B and its titer. RESULTS: Recombinant eukaryotic expressing vector, namely pTB30s, constructed successfully based on the gene encoding secreted form of Mycobacterium tuberculosis Ag85B; pTB30s induced high titer specific antibody against Ag85B in immunized mice. CONCLUSION: pTB30s as DNA vaccine should be further studied to confirm its stimulating role in cell-mediated immune responses in TB prevention. PMID- 11758172 TI - [Rapid detection of Mycobacterium tuberculosis resistance to rifampin using DNA chip]. AB - OBJECTIVE: To develop a new method, DNA chip, which can be used for rapid detection of Mycobacterium tuberculosis resistance to RFP. METHODS: Designing probe according to the sequence of Mycobacterium tuberculosis rpoB gene and fabricating DNA chip. The DNA fragment which contains hot mutation sites of rpoB gene was labelled with cy5 fluorescence and amplified by PCR technique. Then it was hybridized with DNA chip. DNA sequence was used as the control. RESULTS: 14 strains were detected out of 17 randomly selected Mycobacterium tuberculosis resistant to RFP using DNA chip. The efficiency was 83%. A little bit DNA in the sick sputa was sufficient for drug resistance detection without being incubated. CONCLUSION: It showed higher specialty and sensitivity using DNA chip to detect Mycobacterium tuberculosis resistance to RFP. This method was rapid and accurate and could be used for clinical detection of RFP-resistant strains. PMID- 11758173 TI - [P-selectin and tumor metastasis]. PMID- 11758174 TI - [Cytokine network and tuberculosis]. PMID- 11758175 TI - [Improving the diagnosis and treatment of sexual transmitted disease in pregnancy]. PMID- 11758176 TI - [Syphilis in pregnancy women]. AB - OBJECTIVE: To investigate obstetric treatment and pregnancy outcomes of syphilis infection during pregnancy. METHODS: 64 pregnant women diagnosed with syphilis by serological assays were divided into treated group and untreated group according to whether they accepted full-dose treatment against syphilis or not. Patients in the treated group accepted benzathine penicillin(2.4 million units once per week) intramuscular injection for three weeks. The outcome of pregnan after treatment was observed and compared between the two groups. RESULTS: There were 5 cases of primary syphilis (7.8%), 29 cases of secondary syphilis (45.3%), and 30 cases of latent syphilis (46.9%) among the 64 cases. The occurrences of premature birth, fetal intrauterine death, and stillbirth were 0, and 3 cases of congenital syphilis in total 13 cases who carried pregnancy to term in the treated group; while 4, 11, 3, and 10 in the untreated group respectively. In treated group, the 3 babies with congenital syphilis were born from 10 mothers received treatment after 24 gestational weeks, while no congenital syphilis in the 3 women started treatment before 24 weeks. CONCLUSIONS: Pregnant syphilis is prone to be misdiagnosed because of its slight symptom, so it is especially important to screen syphilis as a routine among high risk pregnant women. Premature, fetal death and congenital syphilis can be well controlled through regular and early treatment during pregnancy, yet congenital syphilis can not be avoided completely. PMID- 11758177 TI - [Treatment of syphilis in pregnancy and its perinatal prognosis]. AB - OBJECTIVE: To investigate the effects of treatment of syphilis in pregnancy on perinatal prognosis. METHODS: Patients of syphilis in pregnancy from Hainan Provincial People's Hospital and Haikou Municipal Maternal and Child Health Center during 1995.1 to 2001.1 were collected for retrospective analysis. Pregnant women with syphilis were divided into treated group and untreated group according to whether they received penicillin anti-syphilis treatment or not during pregnancy. RESULTS: The total number of deliveries in the 2 hospitals during that period was 18,701, and 61 out of 9,805 women screened for syphilis were positive, giving an incidence of 6.2/1000. The perinatal mortality rates were 11.2% in treated group and 83.3% in untreated group, and incidences of congenital syphilis were 17.6% and 72.7% respectively. CONCLUSION: Syphilis in pregnancy is a serious complication to harm the fetus. Screening of syphilis during pregnancy is necessary, and penicillin treatment is effective which may reduce the perinatal mortality rate and the birth of congenital syphilis baby. PMID- 11758178 TI - [Effects of human immunodeficiency virus infection on pregnancy outcome]. AB - OBJECTIVE: To investigate the effects of human immunodeficiency virus (HIV) infection on the pregnancy outcome and the incidence of vertical transmission in HIV-positive pregnant women. METHOD: 86 cases of HIV-positive pregnant women and their infants were evaluated retrospectively, and HIV antibody in peripheral blood was detected using enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with normal control group, the incidences of abortion, preterm birth, low birth weight and small for gestational age babies were 9.3%, 14.0%, 16.3% and 10.5%, respectively (P < 0.05); the occurrence of conditional infections of reproductive tract was also higher (P < 0.05); and the incidence of vertical transmission was 12.8% (P < 0.01). CONCLUSIONS: HIV infection in pregnant women markedly increases the risks of abortion, preterm birth, low birth weight and small for gestational age babies, and elevates the incidence of conditional infections of reproductive tract. The incidence of vertical transmission was 12.8%. These data support that it is very important to provide prenatal care to HIV-infected pregnant women and prevent pregnant women from HIV infection. PMID- 11758179 TI - [The follow-up of 12 pregnant women with anticoagulation therapy after mechanical heart valve replacement]. AB - OBJECTIVE: The article discusses the effect of warfarin on pregnant women and their fetus, and the methods of anticoagulation therapy during pregnancy. METHODS: The pregnancy, delivery, and anticoagulation therapy of 12 pregnant women with mechanical heart valve replacement were followed-up. RESULTS: All the patients received oral anticoagulant therapy during pregnancy. The mean dose of imported warfarin was (2.71 +/- 1.24) mg/d (4 cases); domestic warfarin, (3.14 +/ 0.28) mg/d (6 cases); domestic acenocumarol tablet (3.14 +/- 1.08) mg/d (2 cases). No thromboembolism and major hemorrhage occurred. A total of 8 person/times had minor bleeding. Ten patients had term delivery, 2 had premature birth, No abnormal fetus was observed. Only 1 newborn had low birth weight (2,100 g). CONCLUSION: The anticoagulation therapy with low dosage of warfarin (< 5 mg/d) is safe and convenient for the mothers during pregnancy following mechanical heart valve replacement and has low fetus abnormal rate. PMID- 11758180 TI - [Correction of occipito-posterior by maternal postures during the process of labor]. AB - OBJECTIVE: To investigate the effect on correction of occipito-posterior (OP) by changing maternal posture during labor. METHODS: One hundred normal primigravida with head OP position in the latent phase of labor were randomly divided into 2 groups: Group A (n = 50), women were instructed to lay on the same lateral posture with the fetal spine during labor in order to correct the fetal position from OP to occipito anterior (OA); Group B (n = 50) lay on the opposite side to the fetal spine. The OP position was diagnosed by vaginal examination or B ultrasound, and the course of labor and mode of delivery were observed. RESULTS: Thirty-four women delivered vaginally (68%) in group A, with 27 of them turned to OA position (54%); spontaneously while they were 22 (44%) and 12 (24%) in group B respectively, a significant difference was shown (P < 0.005). The average time interval for the 1st stage was (13.5 +/- 6.5) hour and (17.1 +/- 7.2) hour for group A and B respectively, also a significant difference was noted (P < 0.01). CONCLUSION: To instruct women in labor to take the lateral recumbent position with the same side of fetal spine for correcting OP to OA is an effective method. It may increase vaginal deliveries and shorten the first stage of labor, thus reduce dystocia due to OP position. This method is simple and effective, and maybe adopted in most obstetric units. PMID- 11758181 TI - [Clinicopathological features of malignant ovarian neoplasms arising from ovarian endometriosis: a report of 26 cases]. AB - OBJECTIVE: To clarify the features of malignant ovarian neoplasms arising from ovarian endometriosis. METHODS: A total of 26 women with malignant ovarian neoplasms arising from ovarian endometriosis were analyzed retrospectively. RESULTS: Dysmenorrhea and pelvic mass were the most common clinical features. Among 18 cases who underwent B-ultrasound or color doppler ultrasound examination, solid foci in the pelvic masses were found in 10 cases. The main histologic types of ovarian malignancy were endometrioid adenocarcinoma and clear cell carcinoma. Microscopically atypical endometriosis with the tumors were found in 15 cases. International Federation of Gynecology and Obstetrics stage: stage I 21(81%) cases, stage II 3(12%) cases, stage III 2 (8%) cases. CONCLUSIONS: Clinical diagnosis of malignant ovarian neoplasms arising from ovarian endometriosis in early stage is difficult, and B-ultrasound examination is more valuable for diagnosis. It is suggested that close serutiny of endometrial hyperplasia, cellular atypia and malignancy in ovarian endometriosis be essential to understand the origin and development of malignant neoplasms arising from ovarian endometriosis. PMID- 11758182 TI - [Expression of human leucocyte antigen in ectopic endometrial tissue of endometriosis]. AB - OBJECTIVE: To investigate the human leucocyte antigen (HLA) expression of ectopic endometrial epithelial cells in cases with endometriosis and its role in pathogenesis of endometriosis. METHODS: By immunohistochemical analysis, HLA expression was observed in ectopic endometrial epithelial cells of 25 endometriosis patients. Ectopic endometrial cells were cultured in vitro successfully and the expression of HLA were analyzed by flow cytometry in 10 out of the 25 patients. Eutopic endometrium of 15 normal women were taken as control. RESULTS: (1) Expression of HLA class I molecule on ectopic endometrial epithelial cells of endometriosis measured by the immunohistochemical analysis was lower than those of controls, (4.0 +/- 0.5) score and (1.2 +/- 0.8) score respectively. So was the expression rate by flow cytometry in vitro culture (63.38 +/- 11.88)% and (5.27 +/- 2.88)% respectively (P < 0.01). (2) The expression of HLA class II molecule on ectopic endometrial epithelial cells of endometriosis was significantly increased. The outcome by immunohistochemical analysis was (0.2 +/- 0.1) score (control group) and (4.1 +/- 0.7) score (case group) and by flow cytometry was (7.19 +/- 2.43)% and (58.57 +/- 14.99)% respectively (P < 0.01). CONCLUSIONS: The abnormal HLA expression could play a role in the pathogenesis of endometriosis. PMID- 11758183 TI - [Effect of hormone replacement therapy on hemorheology in postmenopausal women]. AB - OBJECTIVE: Our study is to observe the effects of conjugated equine estrogen (CEE) combined with medroxyprogesterone acetate (MPA) on hemorheology in postmenopausal women in order to evaluate mechanism responsible for the increase in the incidence of cardiovascular disease after menopause and also to provide proper instruction and advice of hormone replacement therapy (HRT) for postmenopausal women. METHODS: 60 healthy postmenopausal women were assigned to 3 groups randomly, 20 cases in each group. Group A: CEE 0.625 mg/d + MPA 2 mg/d + calcium carbonate co. (Ca-D) 600 mg/d. Group B: CEE 0.3 mg/d + MPA 2 mg/d + Ca-D 600 mg/d. Group C: Ca-D 600 mg/d only served as control. Measurements of hemorheological parameters were performed before and 6 months after treatment. RESULTS: After 6 months of HRT, group A: blood viscosity under the shear rate of 94.5 s-1 dropped from (5.23 +/- 0.37) mPa.s to (5.03 +/- 0.43) mPa.s (P < 0.05), plasma viscosity dropped from (1.66 +/- 0.19) mPa.s to (1.58 +/- 0.15) mPa.s (P < 0.05), erythrocyte deformability dropped from (4.76 +/- 0.32) mPa.s to (4.54 +/- 0.34) mPa.s (P < 0.05). Group B: blood viscosity under the shear rate of 94.5 s-1 dropped from (5.10 +/- 0.30) mPa.s to (4.87 +/- 0.30) mPa.s (P < 0.05), erythrocyte deformability dropped from (4.65 +/- 0.34) mPa.s to (4.43 +/- 0.29) mPa.s (P < 0.05). No change was found in the control group. After treatment, the levels of plasma viscosity and fibrinogen in group A were much lower than that in group C (P < 0.05). The whole blood viscosity and plasma viscosity in group B were much lower than that in group C (P < 0.05). Thrombelastogram study demonstrated no change regardless HRT or not (P > 0.05). CONCLUSION: Both different dosages of CEE have favor effects on blood viscosity and erythrocyte deformabillity, which could play the role in preventing cardiovascular disease in postmenopausal women. PMID- 11758184 TI - [The clinical value of surgical-pathological staging for endometrial carcinoma]. AB - OBJECTIVE: To explore the practical value of surgical-pathological staging for endometrial carcinoma. METHODS: Ninety-six patients with endometrial carcinoma accepted primary surgical treatment from January 1995 to December 1999 were analyzed retrospectively in our hospital. The clinical and surgical pathologic staging of these patients were compared. RESULTS: The total differences between clinical and surgical-pathologic staging were 44 cases (45.8%), in stage I 24.0%, stage II 76.9%, in stage III 2 of 5 cases. The metastasis rate of pelvic lymph nodes was 10.3%, in stage I 1 of 16 cases, stage II 14.7%. Fourteen patients (14.6%) with extrauterine pelvic metastasis were found, of which 2 of 19 cases in stage I b, 23.1% in stage II. 9.4% with ovarian metastasis, in stage I a 9.7%, stage II 10.3%. 7.9% with positive peritoneal cytology, in stage I 4.0%, stage II 10.3%. 5.2% with omentum metastasis. 2.1% with appendix metastasis. Clinical stages, depth of myometrial invasions, pathological grades and histological types were related to the extent of pelvic and abdominal cavity by univariate analysis (P < 0.01, 0.05). The first three factors were significantly correlated to dissemination by multivariate (P < 0.05). CONCLUSIONS: The surgical-pathological staging is more accurate than the clinical staging, especial in stage II clinical stage depth of myoinvasion, patho-histological grades were closely related to the dissemination in pelvic-abdominal cavity. The surgical-pathological staging is able to assess prognosis objectively and guide therapy for endometrial carcinoma. PMID- 11758185 TI - [Telomerase activity in cervical cancer and its precursor lesion]. AB - OBJECTIVE: To study telomerase activity in cervical cancer and it's precursor lesion. METHODS: Thirty-six cervical cancer and 16 cervical intraepithelial neoplasia (CIN) specimens were measured for telomerase activity using TRAP-ELISA, and 11 normal cervix, 6 chronic cervicitis and 8 adjacent normal tissue specimens as controls. RESULTS: Mean telomerase activity in CIN, cervical cancer, and controls were 0.398 +/- 0.293, 1.580 +/- 0.819, 0.050 +/- 0.012. There was statistically significant difference among three groups (P < 0.01). Additionally, between patients with lymph node metastases (N+) and patients with tumor-free lymph nodes metastases (N-) a statistically distinct difference in telomerase activity was detected (P < 0.05). Telomerase activity was increasing with the advancing of histologic differentiated grade in invasive cervical cancer. However, no significant relationship was found between telomerase activity and tumor size, clinical stage, histology. CONCLUSIONS: Our data suggest that the reactivation of telomerase is an early event and may play an important role during cervical carcinogenesis and progression. It may be used as a tumor biomarker, helpful for the diagnosis of cervical cancer and CIN. PMID- 11758186 TI - [Laparoscopic surgery in the treatment of early uterine malignancies: a report of 8 cases]. AB - OBJECTIVE: To explore the feasibility of laparoscopic operation as treatment for early malignant uterine tumors. METHOD: Six patients with endometrial carcinoma underwent laparoscopic extensive total hysterectomy and bilateral adnexectomy, and 2 with cervical cancer underwent additional pelvic lymphadenectomy. RESULTS: The mean operating time of the 6 laparoscopic extensive total hysterectomy and bilateral adnexectomy was 220 min, and mean blood loss was 200 ml. The mean operating time of 2 cases underwent additional pelvic lymphadenectomy was 240 min. No organ trauma occurred, and the average post-operative hospital stay was 8 days. CONCLUSION: These results suggest that laparoscopic operation is safe and feasible in treating early stage malignant uterine tumors. PMID- 11758187 TI - [Experimental study on resistance to cisplatin and taxol in human ovarian cancer SKOV3ip1 multicellular aggregates]. AB - OBJECTIVE: To investigate the chemosensitivity of ovarian cancer SKOV3ip1 multicellular aggregates to cisplatin and taxol and to explore the possible mechanisms accounting for the effect. METHODS: Liquid overlay system was employed to obtain multicellular aggregates (MCA). We detected the resistance with trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry. RESULTS: MCA cells showed higher cell viability than monolayer cells (P = 0.045 and P = 0.003, respectively). After 40 mumol/L cisplatin exposure for 12 hours, no clone (> or = 50 cells) was formed. After 10 mumol/L taxol exposure for 12 hours, the clone formation showed significant difference in 100-cell group between multicellular aggregates and monolayer cells (P < 0.05). MCA cells in G0 + G1 phase was significantly increased (P = 0.003). After cisplatin exposure, the apoptosis rate of MCA cells were not significantly changed (P = 0.100), and so were cell cycle profiles. Taxol exposure brought about significantly decreased apoptosis rate in MCA cells (P = 0.012). Abrogation of G2 + M arrest was also showed in MCA cells (P = 0.002). CONCLUSIONS: SKOV3ip1 MCA cells show varying degree but increased resistance to cisplatin and taxol, in particular the latter. Cisplatin has nearly equal cytotoxicity to monolayer and MCA cells. Cell cycle redistribution, abrogation of G2 + M arrest and multicellular-mediated inhibition of apoptosis can partially account for the resistance. PMID- 11758188 TI - [Modulation of multidrug resistance by 1-phenyl-2-palmitoylamino-3-morpholino-1 propanol in SKOV3-adriamycin-resistant cell line]. AB - OBJECTIVE: To study the modulation of mdr1 and P-glycoprotein (P-gp) by 1-phenyl 2-palmitoylamino-3-morpholino-1-propanol (PPMP) in SKOV3-adriamycin-resistant (SKOV3/AdrR) cell line. METHODS: SKOV3/AdrR cells were treated with PPMP, mRNA expression of multidrug resistant (mdr1) gene was analyzed by reverse transcriptase-polymerase chain reaction. Intracellular rhodamine (Rh123) concentration was measured by flow cytometry. RESULTS: PPMP was found to inhibit mdr1 expression of SKOV3/AdrR at the mRNA level. This modulation of gene expression was content dependent and complete inhibition appeared at 25 mumol/L PPMP treatment. PPMP could increase intracellular Rh123 accumulation in SKOV3/AdrR cells. After 15, 25 mumol/L PPMP treatment, Rh123 accumulation in SKOV3/AdrR was markedly enhanced Rh123 fluorescence intensity were 389.98, 426.08 respectively (P < 0.05). CONCLUSIONS: PPMP could modulate mdr1 expression at the mRNA level in a content dependent manner. P-gp mediated outward efflux of cytotoxic agents can be blocked by PPMP in SKOV3/AdrR cell. PPMP possesses multi drug resistance activity in ovarian cancer. PMID- 11758189 TI - [Antitumor effects of cytosine deaminase and HSV-tk double suicide gene with adenovirus mediation on rectal cancer cells]. AB - OBJECTIVE: To study antitumor effects of cytosine deaminase (CD) gene/5 fluorocytosine (5-FC) and herpes simplex virus thymidine kinase(HSV-tk) gene/ganciclovir (GCV) systems on rectal cancer cells with adenovirus mediation. METHODS: CD and HSV-tk double suicide genes were transinfected into HR-8348 rectal cancer cells with recombinant adenovirus mediation. The expression of CD and HSV-tk genes was detected with RT-PCR. Plating efficiency and MTT method were used to evaluate the antitumor effect of CD and 5-FC, HSV-tk and GCV systems. RESULTS: Adenovirus was recombined with pAdCMV-Link1(CD + tk), pAdCMV-Link1(-), pAdCMV-Link1(CD), and pAdCMV-Link1(tk) plasmids respectively. HR-8348 cells were infected with the recombined adenovirus and the high expression of CD and (or) HSV-tk genes was found in the corresponding group of tumor cells. Before use of prodrug 5-FC and GCV, the plating efficiency and survival rate of the cells in each group were without significantly different (P > 0.05). But the plating efficiency and survival rate of the tumor cells in pAdCMV-Link1(CD + tk) transinfection group were more highly inhibited than in control, pAdCMV-Link1(-) (P < 0.01) and single suicide gene transinfection groups (P < 0.05) after use of 5-FC and GCV. Combined of use CD and 5-FC, HSV-tk and GCV systems remarkably inhibited the plating efficiency and growth of tumor cells transinfected with double suicide genes. CONCLUSION: Transinfection of CD and HSV-tk double suicide genes has a powerful antitumor effect. PMID- 11758190 TI - [Telomerase activity in stool of patients with colorectal cancer]. AB - OBJECTIVE: To probe into the method for screening colorectal cancer by the way of stool. METHODS: Telomerase activity in the stool of patients with colorectal cancer was determined by PCR-TRAP. RESULTS: The positive rate of telomerase activity in the stool of patients with colorectal cancer was 62.8%. Its sensitivity, specificity and positive predictive value were 62.8%, 95.7%, and 96.4%, respectively. Telomerase activity in stool was not obviously correlated with Duke's stage, lymphatic metastasis and tumor location. Telomerase activity was also found in the stool sample of a patient with colonic adenoma. CONCLUSION: The determination of telomerase activity in the stool of patients with colorectal cancer contributes to the improvement of screening and diagnosis of colorectal cancer. PMID- 11758191 TI - [Morphology of abdominal aortic aneurysm and its clinical importance]. AB - OBJECTIVE: To investigate the morphology of abdominal aortic aneurysms(AAA) and anatomical importance in endovascular surgery. METHODS: The images of AAA were measured by spiral CT angiography in 30 patients from January 1998 to December 2000. RESULTS: The mean diameter of AAA was 5.9 cm (range: 4.0-12.2). The diameter of AAA was positively correlated with neck angle (r = 0.47, P < 0.05) and negatively correlated with neck length(r = -0.41, P < 0.05). Twelve patients(40%) were anatomically feasible for endovascular repair (EVR); 18 patients were excluded for EVR due to angulated proximal necks (mean 88.8 degrees, range 70 degrees-110 degrees) (16 patients; 53.3%), short neck (1; 3.3%), and unilateral common iliac artery occlusion with thrombosis in neck (1; 3.3%). CONCLUSION: The angulated neck was a major single factor for excluding Chinese patients from EVR. PMID- 11758192 TI - [Diagnosis and management of endoleak after endovascular repair of abdominal aortic aneurysm]. AB - OBJECTIVE: To determine the diagnosis and management of endoleak after endovascular repair of abdominal aortic aneurysm (AAA). METHODS: We analysed retrospectively the data of 37 cases of infrarenal AAA treated by endovascular repair and investigated the reasons, managements, results and prognosis of endoleaks. RESULTS: Of 13 patients with endoleak at stent-graft deployment, 6 developed type I endoleak, 3 type II endoleak, 2 type III endoleak, 1 type IV endoleak, and 1 unknown reason. Type I and III endoleaks disappeared after management with additional techniques. The primary endoleak rate was 13.5%(5/37). Three sealed endoleak, 2 persistent endoleaks and 2 secondary endoleaks were found during follow up. The late endoleak rate was 10.8% (4/37). CONCLUSIONS: Endoleak is a chief complication after endovascular repair of infrarenal AAA. The influencing factors for endoleak include neck morphology, distance, angulation, calcification, stent-graft selection and side branching arteries. Additional procedure and follow up are very important. Techniques to find endoleak include CTA, Duplex and MRA after operation. Endoleak with enlarged aneurysm should be treated actively. PMID- 11758193 TI - [Diagnosis and surgical treatment of peripheral intrahepatic cholangiocarcinoma]. AB - OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of peripheral intrahepatic cholangiocarcinoma (PICC). METHODS: Clinicopathological features, surgical treatment and prognosis of 20 patients with PICC treated in our hospital from 1970 to 1999 were retrospectively analyzed. RESULTS: The patients lacked typical clinical manifestations and some had a history of hepatitis B (35%), cirrhosis (45%), and elevation of serum alpha-fetaprotein (AFP) (25%). The diagnostic rates of ultrasound examination (BUS), CT, MRI and emission computerized tomography (ECT) were 90% (18/20), 94% (17/18), 100% (3/3) and 100% (4/4), respectively. However, the liver lesions detected by these methods needed to be differentiated from hepatocellular carcinoma (HCC), metastatic neoplasm and liver cyst, etc. In all the patients, the resection rate was 60% (12/20) and postoperative overall 1-, 3- and 5-year survival rates were 55% (11/20), 35% (7/12) and 20% (4/20), respectively. The liver resection rates were 83% (11/12), 58% (7/12) and 33% (4/12), respectively. Of the 4 patients who had survived for more than 5 years, 3 had a small liver carcinoma with a diameter less than or equal to 3 cm and one had large nodular liver carcinoma with intact capsule. After operation, all the patients received selective hepatic artery perfusion chemotherapy. CONCLUSION: PICC patients lack specific serum tumor marker can achieve good survival after early detection and curative resection with adjuvant therapies. PMID- 11758194 TI - [Hepatic artery and portal vein dual perfusion chemotherapy in combination with injection of lipiodol-ethanol in treatment of advanced primary hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the therapeutic effects of hepatic artery and portal vein dual perfusion chemotherapy (AVPC) in combination with intratumoral injection of lipiodol-ethanol (IILE) on advanced primary hepatocellular carcinoma (PHC). METHODS: A total of 138 patients with pathologically proven and unresectable PHC were divided into two groups. In group A (n = 80), the patients were treated with PVPC through a hypodermic implanted drug delivery pump. In group B (n = 58), the patients were treated with PVPC + IILE. RESULTS: The total effective rate was 12.6% and 25.9% in group A and group B, respectively. There was a significant difference between the two groups (P < 0.05). The secondary resectable rate was 2.5% and 12.1% in group A and group B, respectively (P < 0.05). The half-, 1- and 2-year survival rates were 56.3%, 45.0% and 21.2% in group A but 81.0%, 61.2% and 39.6% in group B, respectively. There were significant differences bet ween the two groups (P < 0.05). However, there was no marked difference in incidence rate of complications between the two groups (P > 0.05). CONCLUSION: The therapeutic effect of AVPC + IILE on advanced PHC is better than that of PVPC alone. PMID- 11758195 TI - [Electrochemical therapy and implanted ports treatment for unresectable carcinoma of body and tail of pancreas]. AB - OBJECTIVE: To examine the efficacy and safety of electrochemical therapy (ECT) in treatment of patients with unresectable carcinoma of the body and tail of pancreas. METHODS: A total of 18 patients (14 men and 4 women; mean age 57.7) with unresectable carcinoma of the body and tail of pancreas were treated by ECT between May 1989 and June 1996 in our hospital (group A). Another 16 patients (12 men and 4 women; mean age 60.3) were treated by ECT plus intraperitoneal chemotherapy between July 1996 and June 1999 (group B). In group B, ECT was used during the operation. Meanwhile, 300 mg calcium leucovorin (CF), 500 mg 5-FU and 200 mg carboplatin were injected weekly into the abdominal cavity through the implanted ports. Pain was determined by using a 10-point visual analog pain scale (VAS) before and after the treatment, life quality periodically assessed according to the 5-step scale system, and tumor size measured using CT or MRI. RESULTS: All the patients were followed up for 5-30 months (mean = 10 months), showing that there were no operative deaths and such complications such as pancreatic fistula and bleeding in both groups. The tumor size in both groups was decreased to some degree. Ascites in 4 of 6 cases in group B were well controlled, whereas there was no changes in 6 cases of ascites in group A. In group A, the VAS basal score was reduced from 7.4 +/- 1.7 before to 2.66 +/- 1.05 after the treatment and the peak VAS from 9.3 +/- 0.9 to 3.71 +/- 0.96 (P < 0.05). In group B, they were decreased from 7.5 +/- 1.5 to 2.17 +/- 1.23 and 9.2 +/- 0.9 to 3.4 +/- 1.13, respectively (P < 0.01). Significant reduction of VAS score persisted for over 3 months after ECT. The satisfaction rate in group B was 37.5%, 62.5% and 25% in 7 days, 1 month and 3 months, respectively. CONCLUSIONS: ECT is a safe and effective procedure for treatment of unresectable carcinoma of the body and tail of pancreas and in relieving its pain and improving the life quality of patients. Supplementary injection of chemical drugs through drug delivery pump is helpful for control of ascites. PMID- 11758196 TI - [Application of laparoscopic technique in splenectomy]. AB - OBJECTIVE: To investigate the application and effect of laparoscopic splenectomy (LS) in the treatment of spleen diseases. METHODS: Under CO2 pneumoperitoneum, laparoscopic splenectomy was performed on 43 patients. General conditions before and after operation, platelet counting, complications and recovery of patients were studied. RESULTS: Laparoscopic splenectomy was performed without complications in all the patients. In the patients with ITP, the effective rate of LS was 89.3%. The difficulty of operation was identified when the diameter of the spleen was over 15 cm assessed by ultrasonic examination, and the operative time was usually prolonged. CONCLUSIONS: LS is one of the best choices when proper indications exist and good techniques under laparoscopy are provided. PMID- 11758197 TI - [Diagnosis of breast-duct disease by breast duct endoscope]. AB - OBJECTIVES: To study the pathological characteristics of breast-duct disease under breast duct endoscope in diagnosis and treatment of breast diseases. METHODS: The images of breast duct of 62 patients with nipple discharge were obtained by hard breast duct endoscope (Olympus Inc) and computer assistant analysis system. RESULTS: Of the 62 patients, malignant tumor was found in 4, premalignancy in 6, intradutal papilloma in 15, and mammary duct or plasma cell mastitis in 37. CONCLUSIONS: Intraductal lesions of patients with nipple discharge can be observed and be followed up with breast duct endoscope. The accuracy of etiological diagnosis of patients with nipple discharge, after the use of breast duct endoscope can partly modify the indications for operation in patients with nipple discharge. PMID- 11758198 TI - [Microsurgical treatment of foramen magnum tumors]. AB - OBJECTIVES: To review the radiological features, and results of microsurgical treatment of foramen magnum tumors. METHODS: We retrospectively analyzed the results of microsurgical treatment of 31 patients with foramen magnum tumor. Fifteen patients had pathological schwannomas (neurinomas), 13 patients meningiomas, and 3 patients chordomas. According to tumor extension, MRI findings and microsurgical approaches, the tumors were classified in two types. Type I tumors located at the ventral foramen magnum, including those originated from the posterior fossa with minimal enlargement of the ventral or anterior-lateral (15 patients). Type II tumors located at the posterior or lateral foramen magnum, including those arising from the spinal canal with minimal enlargement of the foramen magnum (16 patients). Surgical approaches to tumors in this series included suboccipital posterior approach (18 patients), extreme lateral or transcondylar approach (10), and suboccipital retrosigmoid approach (3). RESULTS: Total removal was achieved in 25 patients, subtotal removal in 5, and partial removal in 1. No operative death occurred. Type I foramen magnum tumors were totally removed in 9 patients, subtotally removed in 5 and partially removed in 1. All of type II foramen magnum tumors were totally removed. CONCLUSIONS: To totally resect type I foramen magnum tumors, extreme lateral transcondylar approach is an optimal choice. Type II foramen magnum tumors can be totally removed with good prognosis. PMID- 11758199 TI - [Experience in surgical treatment of 110 patients with craniopharyngiomas]. AB - OBJECTIVE: To study the effective method for surgical treatment of craniopharyngioma. METHODS: 110 patients with craniopharyngioma were operated on. Their tumors were totally removed. Of the 110 patients, 62 were male and 58 female, with age ranging from 15 to 67 years (mean 34.4 years). Pterional approach was performed in 102 patients, subfrontal approaches in 5, and transcallosum into the anterior third ventricle part in 3. The perforating arteries from the carotid, posterior and anterior communicating and anterior choroidal arteries to the hypothalamic structures were preserved when the tumors were excised by pterional approaches via the parachiasmal opticocarotid, carotidotentorial spaces and by opening the lamina terminals. The neural structures of the third ventricular floor were preserved by the transcallosum approach to the anterior part of the third ventricular floor. The cystic fluid was initially aspirated from cystic tumors, solid portion of the tumor was excised by piecemeal and calcification mass was crushed for removal. RESULTS: Of the 110 patients, 101 had a total removal of tumor, 7 a subtotal removal of tumor, and 3 a partial removal of tumors. The pituitary stalk was preserved in 57 patients, ruptured in 29, and unidentified in 24. In 54 patients with diabetes insipidus after surgery, 52 recovered from 3 months to one year after surgery and only two patients failed to over one year after surgery. 52 patients had normal blood sodium level 3 months after surgery. Three patients after surgery had decreased visual acuity. In 3 patients with oculomotor paralysis after surgery, one failed recover till one year. Two patients after surgery had temporal paralysis of the extremities. All the patients after surgery were followed up for one month to five years (mean, 1.1 years). Four patients died after surgery. CONCLUSIONS: The proper surgical approaches for the removal of craniopharyngiomas are the key to achieve good surgical results and avoid the injury to the hypothalamic structures and the perforating arteries to hypothalamus. PMID- 11758200 TI - [Diagnosis and treatment of spontaneous spinal epidural hematoma]. AB - OBJECTIVE: To evaluate the cause of hemorrhage of spontaneous spinal epidural hematoma (SSEH), its clinical manifestations, MR images, treatment, and prognosis. METHODS: Based on literature review, we retrospectively analysed 6 patients with SSEH in terms of pathogenic mechanism, clinical features, neurological function, and the interval between the onset of SSEH and surgery and prognosis. RESULTS: SSEH was liable to occur in young people, and most of cases were acute. MR imaging showed semilunar space occupying mass in the posterior or posteriolateral part inside the spinal canal. The outcome was closely related to the interval between the onset and surgery, whereas it was not related to age, site and size of the hematoma. The better neurological state before surgery and the shorter interval between onset and operation, the better outcome in such patients. CONCLUSIONS: SSEH may be originated from venous bleeding. The process at onset and clinical manifestation depends on the blood supply of the spinal cord. The optimal diagnostic method is MR imaging. Decompression of spinal cord in time is the key procedure for improving the patients' outcome. PMID- 11758201 TI - [Complications of third ventriculostomy for hydrocephalus]. AB - OBJECTIVE: To explore the reason of complications of third ventriculostomy and the method for reducing complications. METHODS: Fifteen third ventriculostomies and the related complications were analyzed retrospectively. RESULTS: Two patients had ventricular infection, one subdural fluid collection, one obstraction of fenestration site by neoplasm, one delayed herniation due to hematoma-occupied third ventricle. The complications were due to the inferior quality of the equipment and poor experience. CONCLUSIONS: Advanced equipment and understanding of possible complications can reduce complications. PMID- 11758202 TI - [Long-term morphological changes in mucosa of intestinal urinary reservoir]. AB - OBJECTIVE: To investigate the relationship between long-term morphological changes in the mucosa of the intestinal urinary reservoir (IUR) and postoperative complications. METHODS: A total of 25 patients undergoing the replacement of bladder with IUR were followed up. Of these 25 patients, 15 had colonic pouch and 10 ileal pouch. Tissues of IUR were biopsied examined with microscope and transmission electron microscope. RESULTS: In patients with colonic pouch, the glandular depth was (0.17 +/- 0.04) mm and microvillous height (0.35 +/- 0.05) micron, which were significantly lower than those (0.42 +/- 0.04) micron and (0.69 +/- 0.08) mm in the control group. In those with ileal pouch, the microvillous height was (0.70 +/- 0.14) mm, (0.54 +/- 0.10) mm and (1.99 +/- 0.14) mm in the short-term group, long-term group and control group, respectively. As compared with the control group, mucous atrophy in these patients was more severe. Tight junctions of the epithelium in both kinds of pouches were well preserved even in the long-term cases. No remarkable malignant changes were found in the IUR mucosa in all the patients. Meanwhile, no special morphological changes were seen in the patients with metabolic acidosis or pouch calculus. CONCLUSIONS: IUR mucosa has some morphological "adaptive" changes after the operation. Intestinal segments are ideal bladder substitutions. PMID- 11758203 TI - [Intravesical instillation of cytotoxic T-lymphocytes induced by soluble tumor antigen in the prophylaxis of recurrence of bladder cancer]. AB - OBJECTIVE: To explore a new method for preventing the recurrence of bladder cancer. METHODS: With the adjuvant of BCG, cytotoxic T-lymphocytes (CTLs) were induced from human peripheral blood mononuclear cells (PBMC) by bladder tumor soluble antigen which was extracted through salt-infiltrating biochemical procedures from autologous bladder tumor. Intravesical instillation of CTLs together with their supernatants after culture for 8 to 10 days was performed in 37 patients with superficial bladder cancer after surgery. The effects of the treatment were evaluated by endocytoscopy, pathological examinations and ELISA assays for the levels of cytokines IL-2, TNF-alpha and IFN-gamma in the patients' serum and urine. The distribution of T-lymphocyte subpopulations was also monitored by SAP immuno-histochemical techniques. RESULTS: The proportion of CD3+ and CD4+ T-lymphocyte subpopulations increased significantly while CD8+ T lymphocyte subpopulation was stable. The ratio of CD4+ to CD8+ increased to 1.60 +/- 0.29. The levels of cytokines IL-2, TNF-alpha and IFN-gamma in serum and urine increased significantly, especially the level of TNF-alpha in urine. Pathological studies revealed that non-specific inflammation is the major change in the bladder mucosa after therapy. Follow-up for 6-26 months showed that 1 patient havd moderate heterogeneity in bladder mucosa. The recurrence rate was 2.7%. Side effects were not found except transient lower fever or hematuria. CONCLUSION: Intravesical insitillation of CTLs could effectively prevent the recurrence of superficial bladder cancer after the improvement of immunological reactivity in the whole body. PMID- 11758204 TI - [Primary Zweymuller total hip arthroplasty for osteoarthritis secondary to congenital acetabular dysplasia]. AB - OBJECTIVE: To evaluate the effectiveness of Zweymuller prothesis in replacing osteoarthritis secondary to congenital dysplasia of the hip. METHODS: From January 1996 to June 2000, Zweymuller prothesis was used to reconstruct 32 hips in 29 patients with congenital acetabular dysplasia(3 bilateral cases). All patients were female. According to the classification of Perner, 19 hips belonged to type I, 7 type II, 5 type III, and 1 type IV. The mean follow-up period was 27.5 months (6-53 months). The preoperative Harris hip score ranged from 25 to 59(average 44.5). RESULTS: The pain was completely relieved, and the Harris hip score ranged from 63 to 97(average 85). CONCLUSION: We consider that the Zweymuller total hip arthroplasty provides stable fixation of the cup in the presence of moderate acetabular dysplasia without structural bone grafting or cementing. PMID- 11758205 TI - [Apoptosis of pancreatic acinar and expression of TNF-alpha mRNA, IL-10 mRNA in rats with acute pancreatitis]. AB - OBJECTIVE: To investigate the apoptosis of pancreatic acinar and the expression of TNF-alpha mRNA, IL-10 mRNA in pancreatic tissue of rats with acute pancreatitis. METHODS: The model of acute edematous pancreatitis(AEP) was established in 20 rats and that of acute necrotizing pancreatits(ANP) in another 20 by injection of sodium taurocholate into the pancreatic duct. Another 10 normal rats were used as controls. At 12 hours after the induction of pancreatitis, 10 rats in each group were sacrificed. Serum and pancreatic TNF alpha and IL-10 levels were measured. The expression of TNF-alpha and IL-10 mRNA in pancreas was detected and the apoptotic rate of pancreatic acinar determined. RESULTS: The apoptotic rate of pancreatic acinar in normal, AEP and ANP groups was 2.98%, 17.29% and 8.39%, respectively. TNF-alpha and IL-10 levels increased after the induction of acute pancreatitis. The level of TNF-alpha was lower while that of IL-10 higher in AEP group than in ANP group. Transcription level of TNF alpha mRNA in ANP group and that of IL-10 mRNA in AEP group were upregulated. CONCLUSIONS: The transcription levels of TNF-alpha and IL-10 mRNA in pancreatic tissue of rats with acute pancreatitis are positively correlated with their levels in serum and pancreas, suggesting that the pancreas is the organ to release cytokines. The apoptotic rate of pancreatic acinar is negatively correlated with the severity of disease and apoptosis may be a benign response to pancreatic injury. PMID- 11758206 TI - [Expression of cytokines in acute heart transplantation rejection]. AB - OBJECTIVE: To observe the expression and changes of local cytokines network in rat heart transplantation so as to determine the role of cytokines in acute rejection of rat heart transplantation. METHODS: The Wistar rats (receptor) were divided into four groups: group A(control, n = 12), group B(IL-2 Mab treated, n = 12), group C [Cyclosporine A (CsA) treated, n = 12] and group D(IL-2Mab + CsA treated, n = 12). Hearts from SD rats were transplanted into a cervical location in Wistar. The local expression of IL-1 beta, IL-2, CD25, IL-4, IL-5, IL-6, IL 10, TNF alpha, IFN gamma was examined at 1, 3, 5, 7, 9, 11, 14 days after operation by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Allografts survival time was (8.3 +/- 1.7) days in group A, (29.2 +/- 7.1) days in group B, (26.4 +/- 5.7) days in group C, (55.0 +/- 10.6) days in group D. The expression of IL-1 beta, IL-4, IL-10, IFN gamma was up-regulated, and the expression of IL-2, CD25, IL-5, IL-6, TNF alpha was significantly inhibited in group A. The expression of IL-1 beta, IL-5, IL-6, IL-10, IFN gamma was up regulated, and the expression of IL-2, IL-4, TNF alpha was significantly down regulated in group B. The expression of IL-1 beta, IL-2, CD25, IL-5, TNF alpha, IFN gamma was up-regulated, and the expression of IL-4, IL-6, Il-10 was significantly down-regulated in group C. The expression of IL-4, IL-5, IL-6, IL 10 was up-regulated, and the expression of IL-1 beta, IL-2, CD25, IFN gamma, TNF alpha was significantly down-regulated in group D. CONCLUSIONS: Cytokines play an important role in the development of acute transplantational rejection. Different cytokines play different roles in different local environments; the main principle possibly is immune deviation. PMID- 11758207 TI - [Effects of Fas ligand expression on pancreatic islet allografts]. AB - OBJECTIVE: To investigate the immune privilege of islet allgrafts induced by the Fas ligand (FasL) expressed by co-transplanted testicular Sertoli cells and the effects of FasL gene transfected into islet cells on pancreatic islet allografts. METHODS: The allogeneic islets and testicular cells from rats were co transplanted into diabetic recipients. Pancreatic islet cells were firstly infected with the recombinant adenovirus AdV-FasL and then transplanted into the diabetic recipients. Allograft survival, islet function and apoptosis of infiltrative lymphocytes in allografts and gene-transfected islet allografts were observed. RESULTS: All the animals receiving islet allografts alone returned to a diabetic status in several days (mean survival time = 6.3 +/- 0.56 days). When the number of testicular cells co-transplanted with islets increased to 1 x 10(7), all the animals remained normoglycemic throughout the follow-up period (P < 0.05). Sertoli cells expressing FasL induced apoptosis of infiltrative lymphocytes in the allografts. In the group of FasL gene transfection, the rejection of allografts was accelerated and the allograft survival time shortened to 3.4 +/- 0.24 days (P < 0.05). Pancreatic islets infected with AdV-FasL demonstrated positive staining for FasL at the 24th hour and increased intensity at the 48th hour after transplantation. After the transplantation, apoptosis of FasL-transfected islet cells occurred. CONCLUSIONS: Co-transplantation of testicular Sertoli cells expressing FasL and islets can induce apoptosis of activated lymphocytes and allows long-term survival of allogeneic islets because of immune privilege. However, direct expression of FasL by islet allografts infected with AdV-FasL accelerates the islet rejection by islet cell apoptosis and granulocytic infiltration. PMID- 11758208 TI - [Changes in plasma free amino acid concentrations in rats during sepsis]. AB - OBJECTIVE: To explore the relationship between plasma free amino acid concentrations and skeletal muscle proteolysis in rats during sepsis. METHODS: An animal model of sepsis in rats was established by administering endotoxin into the peritoneal cavity. The plasma concentrations of free amino acid, ALT, AST, cortisol, TNF-alpha and IL-6 were determined. The rats were randomly divided into normal control, 2, 6, 12 and 24 h groups after administration of endotoxin(8 rats for each group). RESULTS: The total plasma free amino acids concentrations fluctuate within normal range within 24 h after administration of endotoxin. A marked decrease in BCAA (branch-chainamino acid) was observed at 2, 6 and 12 h after administration of endotoxin, but aromatic amino acids (AAA) increased in varying degrees. BCAA/AAA was lower at 2 h and 6 h as compared with that of the normal control, while Phe/Tyr increased obviously at every time point. Lys, Sar, Cys and P-Ser showed no significant changes within 24 h after the administration of endotoxin. Thr, Glu, Orn, His, 3-MH and Ala increased during sepsis, and other amino acids more or less decreased. Plasma concentrations of ALT, AST, cortisol, TNF-alpha and IL-6 obviously increased within 24 h after the administration of endotoxin(P < 0.01). Cortisol peaked at 6 h and IL-6 peaked at 12 h, while TNF alpha at 2 h. CONCLUSION: The results suggested that metabolic disorder of plasma free amino acids during sepsis is due to enhancement of skeletal muscle proteolysis and liver overloading. PMID- 11758209 TI - [Studies on the relationship between clinicopathological features and human papillomavirus types in female lower genital tract carcinoma]. AB - OBJECTIVE: To investigate the relationship between clinicopathological features and human papillomavirus types in female lower genital tract carcinoma. METHODS: Clinicopathological features of 100 cases of female lower genital tract carcinoma (63 cervical carcinoma and 37 vulvar carcinoma) were studied retrospectively. Standard PCR (HPV type 6/11, 16, 18) was applied to formalin fixed, paraffin embedded sections. RESULTS: There were 54 cases of cervical carcinoma and 33 cases of vulvar carcinoma in the 87 cases of target DNA qualified samples. The HPV detection rate in cervical carcinoma was 83.3%. HPV16 (55.6%) and HPV 18(24.4%) were the predominant types. In vulvar carcinoma, HPVs, mainly HPV 16(70%, 7/10), were detected in basaloid (83.3%, 5/6) and warty carcinoma (83.3%, 5/6), but none in conventional type of keratinized squamous cell carcinoma (0.0%, 0/21). Three of the 6 women with basaloid carcinoma were associated with cervical squamous neoplasia, and the same HPV type was found in both lesions in 2 of the 3 patients with two primary tumors. Four patients with basaloid carcinoma recurred after simple vulvectomy or local excision, but no lymph node metastasis occurred and all were still alive at last follow-up, with a median follow-up of 6.3 years. In contrast, the majority of the women with keratinized squamous cell carcinoma were over 65 years of age, with histologic extensive keratinization and poorer prognosis. CONCLUSIONS: A high detection rate of HPV 16 and 18 was found in cervical carcinoma. However, the sensitivity of HPV in vulvar carcinoma seems to be more related to histologic type. PMID- 11758210 TI - [Histopathology and immunohistochemical expression of precursor lesions of cervical adenocarcinoma]. AB - OBJECTIVE: To discuss the histopathology and immunohistochemical expression in precursor lesion of cervical adenocarcinoma-cervical intraepithelial glandular neoplasia (CIGN). METHODS: Histopathological examination and immunohistochemical study (SP method) were performed on 101 cases of CIGN. RESULTS: Criteria for histological grading of CIGN into three degrees, grade I to III, were proposed according to the hyperchromasia and the stratification of nuclei, number of mitoses and the amount of intracellular mucin. Adenocarcinoma in situ was classified as CIGN-III. 46.53% (47/101) CIGN showed a co-existence of CIN (SIL). 45 cases were CEA positive (44.55%) and 38 showed apical and luminal positivity. The positive rate of PCNA was 63.54% and was 100% in CIGN-III. The positive rate of ER was 81.48% (66/81). The expression of ER was often decreased or missing in certain cases. The positive rate of HPV 6/11 in CIGN I-III was 34.09% (30/88), 31.82% (28/88), and 3.41% (3/88), respectively. CONCLUSIONS: Histological grading of CIGN is important. Immunohistochemical staining for CEA, PCNA and ER may be helpful in diagnosis and differential diagnosis of CIGN. PMID- 11758211 TI - [Clinicopathologic analysis of ovarian serous and mucinous borderline tumors]. AB - OBJECTIVE: To understand the clinicopathological features of ovarian borderline tumors and evaluate the significance of various histological appearances. METHODS: Forty-five patients with borderline tumors were analyzed retrospectively. The stage distribution was stage I, 34 patients, stage II, 4 patients and stage III, 7 patients. RESULTS: Forty-five cases of borderline tumors accounted for 25.4% of ovarian epithelial malignant tumors. The ratio of serous borderline tumors (SBTs) to mucinous borderline tumors (MBTs) was approximately 1:1.3. Nine of eleven SBTs with exophytic growth presented peritoneal implants, of which two were invasive and seven noninvasive. Two SBTs and 1 MBT recurred after 5, 4, and 1 years respectively. Thirty-three cases were followed from 2 to 9 years. The 5-year survival rate was 100% (Kaplan-Meir method). CONCLUSIONS: The prognosis of the SBTs is favorable. SBTs with exophytic growth are often associated with peritoneum implants. PMID- 11758212 TI - [Significance on expressions of Annexin-I and its correlative gene proteins in endometrial hyperplasia, atypical hyperplasia and endometrial carcinoma]. AB - OBJECTIVE: To investigate expression of Annexin-I in various endometrial lesions and its significance in differential diagnosis of endometrial borderline lesions. METHODS: We collected 37 specimens with different endometrial lesions, and reclassified them according to China and FIGO's standard, which included 12 cases of endometrial hyperplasia (EH), 10 cases of atypical hyperplasia (ATH) and 15 cases of endometrial carcinoma (EC). Immunohistochemical staining for AX-I, c erbB-2, p53 protein, ER, PR, EGF and IGF were performed by LSAB. RESULTS: The results showed that for AX-I, 1 cases of EH was weakly positive and others were negative; 9 cases of ATH showed strong positivity in the cytoplasm and the cell membrane, and 1 weakly positive; 7 cases of EC were positive and 8 negative. c erbB-2 was expressed in 9 cases of ATH and 1 was negative. Expressions of EGFR, ER and PR were strong in all cases, but IGFR was negative in almost all cases. P53 expression was higher in EC than in ATH. CONCLUSIONS: AX-I expression suggests that (1) AX-I protein may play an important role in the pathogenesis of cancer, the expression decreased and disappeared after malignant change. (2) High expression for AX-I can be used to differentiate ATH and EC. In addition, c-erbB 2 expression appeared to parallel the expression of AX-I in both ATH and EC, but in ATH it was higher than that in EC. PMID- 11758213 TI - [Investigation of the clinicopathologic features, immunophenotype and Epstein Barr virus infection of primary central nervous system lymphoma]. AB - OBJECTIVE: To investigate the clinicopathological features, immunophenotypes and EB virus infection of 25 cases of primary central nervous system lymphoma (PCNSL). METHODS: Immunohistochemical staining was performed using monoclonal antibodies, L26 (CD20), kappa,lambda for B lymphocytes, UCHL-1 (CD45RO) for T lymphocytes, CS1-4 for latent membrane protein-1 (LMP-1) and GFAP for gliocytes. In situ hybridization was used for detection of EB virus encoded small nuclear RNAs (EBER1/2). RESULTS: All of the 25 PCNSL were of B lymphocyte origin with high-grade malignancy. Only 2/25 (8%) cases showed positive signal in EBER1/2 in situ hybridization. CONCLUSION: This group of PCNSL were all B-cell lymphomas, and the role of EB virus in this group of PCNSL was uncertain. PMID- 11758214 TI - [Pathological observation of 16 cases with non-epithelial tumor and tumor-like lesions of the prostate]. AB - OBJECTIVE: To investigate the diagnosis, differential diagnosis and prognosis of stromal tumors and tumor-like lesions of the prostate. METHODS: By means of HE, immunohistochemistry and electron microscopy, the clinical and histological data of 16 cases with stromal tumors and tumor-like lesions of the prostate were observed. Some of them were followed-up. RESULTS: Of the 16 cases, 6 presented stromal nodular hyperplasia, 3 were stromal sarcoma, 1 malignant phyllodes-type tumor, 3 leiomyosarcoma, 1 fibrosarcoma, and one non-Hodgkin's lymphoma. CONCLUSIONS: Nearly all the leiomyomas of the prostate diagnosed previously are, in fact, stromal nodular hyperplasia. The phyllodes-type tumors are often confused with stromal sarcomas in needle biopsy specimens and cause difficulty in differential diagnosis. Diagnostic criteria of leiomyosarcoma, fibrosarcoma, non Hodgkin's lymphoma of the prostate are the same as their counterparts in the soft tissue. Non-epithelial malignant tumors in prostate are of poor prognosis. PMID- 11758215 TI - [Antigen receptor V beta gene usage of T lymphocytes in diseased thyroids in patients with autoimmune thyroid diseases]. AB - OBJECTIVE: To explore the patterns of TCR V beta gene families and the preferentially used V beta genes in intrathyroidal T lymphocytes (ITL) of patients with Graves disease and Hashimoto thyroiditis. METHODS: Thyroid tissues of 12 patients with Graves disease, and 15 patients with Hashimotos thyroiditis were used for RNA extraction. Then, the RNA was used as templates for RT-PCR with a panel of primers including 24 oligonucleotides specific for TCR V beta gene families as upstream primers and one oligonucleotide specific for C beta as downstream primer. The amplified products were subjected to electrophoresis in agarose gels and observed under UV light. The positive expression of TCR V beta gene was identified by comparing the products with the size of the designed V beta genes. The matched peripheral blood samples of 5 Graves patients, 5 Hashimoto thyroiditis patients and 7 normal subjects were also obtained and used as controls. RESULTS: In 24 TCR V beta gene families tested for each individual sample, their average expressions were 5.3 +/- 1.2 and 13.4 +/- 3.0 in thyroid specimens of patients with Graves disease and Hashimoto thyroiditis, respectively, while those in the matched peripheral blood lymphocytes of the above two groups and normal controls were 23.0 +/- 1.0, 22.2 +/- 1.3 and 22.4 +/- 1.7, respectively. In addition, some of the TCR V beta genes such as V beta 3, V beta 5 and V beta 8 were more frequently used by intrathyroidal lymphocytes of Graves disease. CONCLUSIONS: These data indicate the oligoclonality of the intrathyroidal T cell populations in patients with Graves disease. Also, those of the preferentially used TCR V beta genes can be regarded as molecular targets for specific immune intervention. In contrast, the loss of restriction of TCR V beta gene utilization exists in Hashimoto thyroiditis, which may be related to the recruitment of T lymphocytes in thyroid glands through this mechanism. PMID- 11758216 TI - [Detection of proteins and mRNA of p16, p53 and nm23 in mucoepidermoid carcinoma of salivary glands and their prognostic significance]. AB - OBJECTIVE: To disclose the relationship between the expression of p16, p53 and nm23 and the significant morphologic characteristics in mucoepidermoid carcinoma. METHODS: The proteins and mRNA in paraffin blocks from 41 mucoepidermoid carcinoma patients were studied with immunohistochemical methods and in situ hybridization respectively. RESULTS: The negative expression of p16 was found in 62.5% (15/24) of the low differentiation grade and in 29.4% (5/17) of the high differentiation grade (P = 0.037). The positive p53 expression was detected in 70.8% (17/24) of the low grade neoplasms and in 23.5% (4/17) of the high grade (P = 0.003), while positive nm23 protein was present in 37.5% (9/24) and 64.7% (11/17) respectively (P = 0.086). However, no relationship was found between positive mRNA of p16, p53, nm23 and WHO pathologic grade. CONCLUSIONS: There is a significant correlation between expression of p16 and p53 and WHO pathologic grade of mucoepidermoid carcinoma, which indicates clinical prognostic significance. No correlation is noticed between the pathologic grade and the expression of nm23 protein and mRNAs of p16, p53 and nm23. PMID- 11758217 TI - [Activation of NF-kappa B and its effect on induction of platelet-derived growth factor-B transcription by angiotensin II in ECV304 cell line]. AB - OBJECTIVES: The renin-angiotensin system may contribute to the pathogenesis of atherosclerosis. The transcription factor nuclear factor-kappa B (NF-kappa B) participates in most signal pathways involved in the inflammatory process. In this project the effect of angiotensin II (Ang II) on NF-kappa B activation and the promotion of PDGF-B mRNA expression in human endothelial cell line ECV304 was studied. METHODS: Electrophoretic mobility shift assay, immunofluorescence and immunoelectronic microscope techniques, including confocal microscopy and gold particle labelled electronic microscopy were applied to investigate the mechanism by which Ang II activates NF-kappa B, ECV304 cells were transiently transfected with an NF-kappa B/luciferase reporter gene and catalytically inactive NIK, IKK alpha, IKK beta mutants respectively. Northern blot was carried out to detect PDGF-B mRNA. RESULTS: By the findings of immunofluorescence confocal microscopy, immunoelectronic microscopy and Northern blot, Ang II was effective in stimulating NF-kappa B activation and there was definited cytoplasmic-to-nuclear translocation of NF-kappa B subunits p50 and p65 and overexpression of PDGF-B mRNA expression. Over-expression of the transiently transfected IKK alpha-KM, IKK beta-KM and NIK-KM mutant genes enabled to block the reporter gene activation induced by ang II. CONCLUSION: Ang II is effective to activate NF-kappa B through a pathway dependent on NIK, IKK alpha and IKK beta, and induces PDGF-B transcription in the endothelial cell line ECV304. PMID- 11758218 TI - [Muscle pigment epithelium-derived factor gene associating with tumorigenesis of B16 melanoma]. AB - OBJECTIVE: Random amplified polymorphic DNA (RAPD) analysis was used to detect the genomic variant in B16 melanoma, and to seek the tumor related DNA fragments. METHODS: Genomic DNA from B16 melanoma and C57BL/6J mouse normal tissues were amplified by RAPD with 105 random primers, the significantly different DNA fragments were isolated, cloned and sequenced. DNA sequences were analyzed with GenBank data. RESULTS: 24 of the 105 primers generated polymorphic profiles when the B16 melanoma RAPD profile was compared to that of its normal tissue DNA. By amplification of the primer AB8-5, a tumor band showing loss with respect to normal band was detected and this DNA fragment was designated as B8-5. B8-5 was a 610 bp fragment, the sequencing result of B8-5 showed 99% homology with muscle pigment epithelium-derived factor (PEDF) gene, and 100% homology with muscle pigment epithelium-derived factor mRNA. B8-5 was therefore regarded as PEDF gene. CONCLUSION: Our result found that allelic losses exist in PEDF gene, and therefore suggest that PEDF is associated with tumorigenesis of B16 melanoma. PMID- 11758219 TI - [Pathological development of borderline tumors of ovarian carcinomas]. PMID- 11758220 TI - [Pathological differential diagnosis of small B cell malignant lymphoma]. PMID- 11758221 TI - [p33ING1 gene and its research adrancement]. PMID- 11758222 TI - [Studies on hereditary deficiency of coagulation factor V]. AB - OBJECTIVE: To explore the mechanisms of hereditary deficiency of coagulation factor V (FV). METHODS: The amount of FV in plasma and platelets was assayed by immunological and biochemical method, FV gene analysis by PCR product sequencing and restriction enzyme analysing, and the biostructural pathology of the identified mutation by molecular modeling. RESULTS: No detectable FV fragments and FV activity were found in the plasma and platelets from the proband of the affected family. His gene analysis revealed a 1763A-->C substitution in a FV allele gene. The mutation might cause the loss of the hydrogen bond between conservative Tyr530 and Glu330, and form a cavity in the protein core. CONCLUSION: The 1763A-->C mutation might cause the instability of FV and be the important mechanism for the hereditary deficiency of FV. PMID- 11758223 TI - [A novel gene mutation in a congenital protein S deficiency pedigree]. AB - OBJECTIVE: To study the phenotype and genotype of a protein S (PS) deficiency pedigree. METHODS: Detection of total and free PS antigen was carried out by ELISA, PS activity by coagulation assay, amplification of exon I-XII fragments of PS gene by polymerase chain reaction (PCR), changes of denaturing cDNA by single strand conformation polymorphism (SSCP) and gene mutation by DNA sequencing. RESULTS: In the 9 members of the pedigree, free PS was between 10.3%-45.5% (normal range 55%-128%) and PS activity between 13%-37% (normal range 70%-130%), but total PS was normal. A G to T change in exon X of the protein S gene was identified. This mutation resulted in a substitution of stop codon for Ser. CONCLUSION: It was demonstrated that the proband is heterozygosity and the existance of G163 T change in exon X of the protein S gene led to a substitution of stop codon for Ser. This mutation is a novel undescribed mutation. PMID- 11758224 TI - [Human factor VIII expression in retrovirus vector-transduced bone marrow stromal cells]. AB - OBJECTIVE: To explore the feasibility of bone marrow stromal cells (BMSCs) used for gene therapy of hemophilia A. METHODS: Murine and rabbit BMSCs were transduced with a recombinant replication-incompetent retrovirus LNC-FVIII delta B, which encloses a B-domain-deleted (760aa-1,639aa) human factor VIII cDNA. An optimized protocol involving temperature declining (32 degrees C) and centrifugation was used. Antigen and coagulant activity of human FVIII in the cell culture medium were measured by ELISA assay and one-stage method, respectively. Semi-quantitative PCR was performed for the transduction efficiencies. Western blot was used for FVIII protein analysis. RESULTS: Transduction efficiencies were increased 5- to 8-fold by temperature decline and centrifugation, which resulted in high expression and secretion of FVIII in transduced mouse[(556 +/- 80) ng/10(6) cells/24 hr] and rabbit [480 +/- 56) ng/10(6) cells/24 hr] BMSCs. Coagulant activities of human FVIII secreted from transduced murine and rabbit BMSCs were 2.42 U/10(6) cells/24 hr and 1.8 U/10(6) cells/24 hr, respectively. Western blot analysis demonstrated that the B domain deleted FVIII cDNA was secreted predominantly as heavy and light chain heterodimers that resemble the native forms in human plasma. CONCLUSIONS: It was demonstrated that the BMSCs system has potential utility in the gene therapy for hemophilia A. PMID- 11758225 TI - [A novel point mutation in the transmembrane domain of platelet glycoprotein IX gene identified in a Bernard-Soulier syndrome patient]. AB - OBJECTIVE: To diagnose a patient with Bernard-Soulier syndrome (BSS) and investigate her gene abnormality. METHODS: Platelet size and structure were studied under light and electron microscopies. Platelet membrane glycoproteins (GP) were measured by flow cytometry. PCR and DNA sequencing were used to identify gene abnormality. RESULTS: The patient had thrombocytopenia with giant platelets. Ristocetin-induced platelet agglutination was absent. GP I b/IX complex in the platelet membrane was significantly decreased, which was resulted from an Ala139 Thr substitution in the transmembrane domain of GPIX. CONCLUSION: Ala139 Thr mutation of the GPIX gene in this patient is a novel missense mutation, which has not been reported in BSS. PMID- 11758226 TI - [Study on factor IX gene mutation in 74 hemophilia B patients]. AB - OBJECTIVE: To investigate the distribution of the FIX gene mutations in hemophilia B(HB) and compare the mutation patterns between the Chinese HB and Caucasian HB. METHOD: Genomic DNA was extracted from the blood samples of HB patients. Nine DNA segments of the FIX gene were amplified. Gene mutations of the amplified DNA segments were detected by direct sequencing. RESULT: Fifty eight independent mutations were detected and identified in 69 HB patients. Among them twenty nine mutations were novel and not reported before. A similar pattern of germline mutation was found in both Chinese HB and Caucasian HB patients. CONCLUSION: No difference was observed in mutation patterns between Chinese and Caucasian HB. PMID- 11758227 TI - [Study on the mechanism of thrombosis by lupus anticoagulant inhibited protein C pathway]. AB - OBJECTIVE: To study the mechanism of thrombosis in systemic lupus erythematosus (SLE) patients with protein C (PC) pathway inhibition by lupus anticoagulant(LA). METHODS: Phosphoethylamine(PE) dependent activated protein C (APC) inhibiting assay (modifed DRVVT) was used to observe the inhibition of APC activity after incubation of IgG from both normal and SLE patients with PE. RESULTS: The activity of anticoagulation of APC was augmented by PE. Proportionally to its concentration, LA could inhibit the PE dependent anticoagulation of APC. The inhibition of LA-IgG on APC in the LA positive SLE patients with thrombosis was stronger than that in LA negative non-thrombosis patients; but IgG has no effect on the APC activity in normal person. CONCLUSION: LA inhibiting the PC pathway by interfering with PE may be the important reason of thrombosis in SLE patients. PMID- 11758228 TI - [The relativity study of thrombopoietin and chronic idiopathic thrombocytopenic purpura]. AB - OBJECTIVE: To explore the relationship between thrombopoietin (Tpo) levels and reticulated platelet (RP), blood platelet count (BPC), maturity of megakaryocytes in patients with chronic idiopathic thrombocytopenic purpura (CITP), and the prediction evaluation according to Tpo levels. METHODS: Serum level of Tpo was measured by a sandwich-ELISA procedure, RP by flow cytometry after stained with thizole orange (TO), and maturity of megakaryocytes by laser scanning confocal microscopy (LSCM). RESULTS: The serum level of Tpo was (204.05 +/- 65.70) ng/L in 23 normal controls and (345.46 +/- 222.23) ng/L in 33 patients with CITP, being no significant difference between the two groups (P > 0.05). Compared with controls, serum Tpo levels in 22 aplastic anemia(AA) patients [(1427.62 +/- 468.84) ng/L] and 10 acute myelogenous leukemia (AML) patients [(596.09 +/- 462.95) ng/L] were increased significantly (P < 0.05). The RPC was significantly lower in AA and AML patients (P < 0.05). The RP% was increased significantly in CITP and AML patients (P < 0.05). The Tpo level was higher in CITP patients with no response to glucocorticoid therapy than in those with response (P < 0.05). CONCLUSION: Serum level of Tpo was not increased in patients with CITP. The RP%, RPC and Tpo levels could reflect thrombocytopoiesis and differentiate the causes of thrombocytopenia. The serum level of Tpo could be useful in prediction of the response to therapy in CITP patients. PMID- 11758229 TI - [Hypercoagulation aggravates renal dysfunction in patient with diabetic nephropathy]. AB - OBJECTIVE: To investigate the relationship of hypercoagulation and renal dysfunction in patients with diabetic nephropathy(DN). METHODS: Forty six diabetes type II patients with nephrotic syndrome were divided into 3 groups according to 24 hr creatinine clearance (Ccr) as high, middle and low groups. Fourteen of the 46 patients received warfarin therapy. The parameters of coagulation and fibrolysis as well as renal function were examined. RESULTS: Patients with moderate and major renal dysfunction (M group and L group) displayed higher activities of coagulation than those with mild renal dysfunction (H group) did. Warfarin could obviously improve the status of coagulation and fibrolysis in patients with DN and delay the progress of renal dysfunction. CONCLUSION: Hypercoa-gulation was one of the causes of renal dysfunction in patients with DN. PMID- 11758230 TI - [Effect of platelet on procoagulant activity of monocyte]. AB - OBJECTIVE: To investigate the effect of platelet on procoagulant activity of mononcyte(M). METHODS: The procoagulant activity of M lysates was measured by one stage clotting time assay, the tissue factor (TF) activity and the role of P selectin were confirmed by specific monoclonal antibodies (McAb). RESULTS: 1. Activated M challenged by lipopolysaccharide(LPS) had augmented procoagulant activity and this effect was blocked by TF McAb. 2. Procoagulant activity of M and activated M increased significantly with the presence of activated platelets. 3. The enhancement effect of activated platelet on the procoagulant activity of M was blocked by P-selectin McAb. CONCLUSION: TF expression of M contributes to the procoagulant activity of Ms and activated platelet enhances the procoagulant activity via P-selectin. PMID- 11758231 TI - [Clotting factor X deficiency resulted from an T 58-->G mutation within exon 1 of human factor X gene]. AB - OBJECTIVE: To identify the genetic defect of a patient with clotting factor X deficiency (QGZ). METHODS: PCR and DNA sequencing were used to screen mutation in factor X gene. PCR primers were designed covering all the coding regions for exon and flanking intron sequences. RESULT: A single nucleotide substitution T 58G in exon 1, which caused a missense mutation Ser(AGT) 11 Arg(AGG) in signal peptide, was identified by DNA sequencing. CONCLUSION: This nucleotide substitution might be the molecular etiology of factor X deficiency. PMID- 11758232 TI - [Study on homocysteine metabolism related enzymes gene mutations in Chinese patients with ischemic cardiovascular and cerebrovascular diseases]. AB - OBJECTIVE: To explore the significance of gene mutations of cystathionine beta synthase (CBS844ins68), methionine synthase (MS A2756G) and methylenetetrahydrofolate reductase (MTHFR C677T) in ischemic cardiovascular and cerebrovascular diseases. METHODS: The genotypes of CBS 844ins68, MS A2756G and MTHFR C677T were determined by PCR-based assay in 102 patients with brain infarction, 73 with myocardial infarction and 100 healthy controls. RESULTS: The prevalences of CBS 844ins68 and MS A2756G in the cohort studied were somewhat lower than that in western Caucasian populations. There were no significant differences in the frequencies of CBS 844ins 68, MS A2756G and MTHFR C677T mutations between the patient the and control groups. However, the heterozygous form of CBS 844ins 68 tended to be more prevalent in the controls than in the patients. CONCLUSION: Gene mutations as CBS 844ins 68, MS A2756G and MTHFR C677T may not be independent risk factors for ischemic cardiovascular and cerebrovascular disease in Southern Chinese Han population. The prevalences of CBS 844ins 68 and MS A2756G may vary with different ethnic groups or geographic regions. PMID- 11758233 TI - [Further rationalization of anti-bacterial pharmacotherapy]. PMID- 11758234 TI - [Thinking about the specific cyclooxygenase-2 inhibitors since its recommendation]. PMID- 11758235 TI - [Clinical analysis of nosocomial infection of extended spectrum beta-lactamase producing bacteria]. AB - OBJECTIVE: To investigate the clinical characteristics of nosocomial infection of extended spectrum beta-lactamase(ESBL)- producing bacteria. METHODS: The data of 50 cases of ESBL(+) E. coli and K. pneumonia from January to November 1999 in Peking Union Medical Hospital were analysed; 45 cases of ESBL (-) infection were randomly selected as controls. t-test and chi-square tests were used for statistical analysis. RESULTS: Long time hospitalization and use of the third generation cephalosporins were risk factors for ESBL(+) pathogen infection(P < 0.02); the prevalence of ESBL(+) bacteria infection in abdominal and pelvic cavity was higher than that of ESBL(-) bacteria(P < 0.02); the outcome of properly treated group(sensitive antibiotics were used within 72 hours) was much better than improperly treated group. All ESBL(+) bacteria were sensitive to imipenam, the resistance rate of ESBL(+) bacteria to cefmetazole, amikacin and piperacillin/tazobactam was low; the in vitro activity of ceftazidim to ESBL(+) bacteria was high but the in vivo activity is still under study. CONCLUSION: The mortality of ESBL(+) bacteria infection was high; the outcome would be improved if sensitive antibiotics were chosen as soon as the diagnosis was made. PMID- 11758236 TI - [The assay of beta-lactamase activity in Pseudomonas aeruginosa biofilm]. AB - OBJECTIVE: To analyze the resistance mechanism of Pseudomonas aeruginosa biofilm bacteria. METHODS: An in vitro model of Pseudomonas aeruginosa bacterial biofilm was established in silicon disk with modified flat-board method and a rapid staining procedure of AgNO3 was used to verify it. Biofilm was observed under scanning electron microscopy. The test was carried out in three groups. Group A was planktonic bacteria of Pseudomonas aeruginosa, group B biofilm bacteria of Pseudomonas aeruginosa and group C biofilm bacteria induced by imipenem. The activity of beta-lactamase was quantitated with a spectrophotometric assay method and beta-lactamase quantitation was determined by using Bio-Rad protein assay. RESULTS: The activity and protein content of beta-lactamase in group B was higher than that in group A by 4.67 and 2.09 times. The activity of group C was 21.86 times as much as that in group A and 4.68 times as much as that in group B. The quantitation in group C was 6.28 times as much as that in group A and 3.00 times as much as that in group B. The activity and quantitation of the three groups were different significantly from each other (P < 0.01). CONCLUSION: The production of beta-lactamase in Pseudomonas aeruginosa biofilm bacteria is one of the main reasons of its resistance. PMID- 11758237 TI - [A randomized, controlled clinical trial of meropenem and imipenem/cilastatin in the treatment of acute bacterial infections]. AB - OBJECTIVE: Meropenem is a new carbapenem antibiotic developed by Sumitomo Pharmaceuticals and shown to resist degradation by renal dehydropeptidase I (DPH I), an enzyme which exists chiefly in the kidneys and decomposes carbapenem antibiotics. It has a powerful antibacterial activity with broad antibacterial spectrum. The objective of the study is to evaluate the efficacy and safety of meropenem. METHODS: A randomized, open-label, controlled study was conducted for treating patients with bacterial infections. A total of 112 hospitalized patients were enrolled in the study. 55 patients received meropenem 500 mg every 12 hours (or 1g every 12 hours if necessary) and 57 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1g/1g every 12 hours if necessary) intravenously. The duration of treatment was 7-14 days in both groups. RESULTS: 42 of the 55 cases receiving meropenem and 41 of the 57 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rate was 88.1%(37/42) for the meropenem group and 85.4%(35/41) for the imipenem/cilastatin group, whereas the bacterial eradication rate was 81.1%(30/37) and 84.2%(32/38), respectively. 47(69.1%) of 68 strains isolated from patients produced beta-lactamase. Adverse drug reaction was evaluated in 44 cases of the meropenem group and 41 cases of the imipenem/cilastatin group. The adverse drug reaction rate was 13.6%(6/44) and 12.2%(5/41), respectively. The results showed that there were no statistical differences between these two groups (P > 0.05). CONCLUSION: Meropenem and imipenem/cilastatin were effective and safe for the treatment of lower respiratory tract infections and urinary tract infections and other infections caused by beta-lactamase-producing strains. PMID- 11758238 TI - [Retrospective analysis of 15 patients with fungal septicaemia]. AB - OBJECTIVE: Study on the early diagnosis, antifungal therapy, and prophylaxis for fungemia. METHOD: Retrospective study of the clinical features, treatment and outcome of 15 patients with fungemia from August 1992 to September 2000 at Peking Union Medical College Hospital. RESULTS: The patients' ages ranged from 25 days (1 newborn) to 72 years (mean: 54.5 years in 14 patients); 11 were male. The length of hospitalization before fungemia varied from 7 days to 12 months (median: 1.5 months) in 14 patients who fulfilled criteria for nosocomial fungemia, another one with fungemia occurred outside of hospital. The main underlying conditions were: malignant disease (cancer, leukemia and acute aplastic anemia) in 10 patients (66.7%), infections following abdominal surgery in 2 patients (13.3%), trauma in 1 patient, rheumatic heart disease in 1 patient and 1 newborn. In this group the risk factors for fungemia included: prior antimicrobial therapy (14 of 15, 93.3%), steroids/cytotoxic chemotherapy (11 of 15, 73.3%), neutropenia (4/15, 26.7%), central venous catheterization and hyperalimentation (2 of 15, 13.3%). There were two or more risk factors in each of 11 patients. Fungal species isolated from 15 patients were: C. albicans (in 4), C. tropicalis (in 3), C. parapsilosis (in 3), C. sake (in 1), Trichosporon beigelii (in 1) and Yeast-like fungus (in 3). Before or during of fungemia, there were abnormal pulmonary signs or chest roentgenogram in 11 (73.3%), thrush in 2 (13.3%), enteritis in 2 (13.3%), urinary tract infection in 2 (13.3%) and endocarditis in 2 (13.3%). The overall mortality was 53.3% (8 of 15) and was 26.7%(4 of 15) duo to fungemia. Out of 7 survived patients, 4 were cured, 3 with fluconazole (length of therapy: 3-5 weeks) and 1 with a combination therapy of amphotericin B plus fluconazole (length of therapy: 3 months), other 3 were improved with fluconazole or amphotericin B (length of therapy: > 2 weeks). During the antifungal therapy, 2 patients with the complication of fungal endocarditis underwent surgical removal of vegetation on the infected valves. CONCLUSION: In this study, the most frequent infectious agents were Candida albicans and non-albicans Candida species. Early diagnosis is of importance to guide appropriate antifungal therapy and reduce mortality. PMID- 11758239 TI - [An epidemiological survey of thyroid disorders in an area with high iodine content in water supply]. AB - OBJECTIVE: To investigate the status of thyroid disorders among people aged 14 years and older residing in Huanghua County, an iodine excess intake area in north China. METHODS: 4,230 people were asked to fulfill the questionnaire and 1,074 among them aged (36.97 +/- 12.83) years were accepted to be samples for the test. All subjects who were taken as samples needed to fill the questionnaire on thyroid disorders in detail, accept physical and ultrasound examination. Their morning fasting urine were collected for measurement of iodide concentration, and their sera were measured for thyroid-stimulating hormone(TSH, the third generation), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) and thyroglobulin (TG). If some people had abnormal TSH level, their free T4, free T3 and TSH receptor antibody(TRAb) were measured. RESULTS: The median level of urinary iodide of the sample subjects was 614.61 micrograms/L. The prevalence of clinical and subclinical hyperthyroidism was 1.21% and 1.12% respectively; 92.3% of the clinical hyperthyroidism were of Graves' disease and 75% of the subjects with subclinical hypothyroidism were TRAb positive. The average incidence of clinical hyperthyroidism was not different between 2 periods before and after general iodinization of table salt in this area (1991-1995 and 1996 2000). The prevalence of clinical and subclinical hypothyroidism was 1.96% and 6.05% respectively. All the clinical patients were female, among them 85.71% were TPOAb and/or TGAb positive, while only 29.23% of the subclinical patients were TPOAb and/or TGAb positive. Positive TPOAb and TGAb were seen in 11.6% and 9.3% respectively of the sample subjects with an age-related increase. Positive thyroid autoantibody was more common in the female and those with abnormal TSH. The prevalence of thyroid cancer during the period of 1994-2000 was 91.58/100,000. CONCLUSION: The high prevalence of hypothyroidism and thyroid cancer indicates that excessive iodine intake in this area is not safe. PMID- 11758240 TI - [Apoptosis of myocardial cells in dilated cardiomyopathy]. AB - OBJECTIVE: To study apoptosis of myocardial cells in dilated cardiomyopathy (DCM) and its relation with cardiac function. METHODS: Myocardial samples of 21 patients in a DCM group were obtained from hearts of 14 patients undergoing endomyocardial biopsy (EMB) in right ventricular (EMB sub-group) and from the hearts of the 7 remaining patients at autopsy (Autopsy sub-group). Myocardial samples of a control group were obtained from hearts of 5 patients at autopsy, who died of causes other than cardiovascular disease. Apoptosis was evaluated histochemically by in situ end-labeled DNA (Tunel method). RESULTS: (1) Apoptotic index (AI) of the DCM group was significantly higher than that of the control group(P < 0.01), AI of EMB sub-group was significantly lower than that of autopsy sub-group (P < 0.01), but significantly higher than that of the control group (P < 0.01). (2) AI in patients with heart-thorax ratio (HTR) < 0.6, left ventricular end diastolic diameter (LVDd) < 65 mm and left ventricular ejection fraction (LVEF) > or = 40% was significantly lower than that of patients with HTR > or = 0.6, LVDd > or = 65 mm and LVEF < 40% respectively (P < 0.01 for all), but was significantly higher than that of the control group respectively (P < 0.01 for all). CONCLUSIONS: Apoptotic myocardial cells were frequently observed in the myocardial tissues of the DCM and the magnitude of apoptosis increased with the deterioration of cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in the DCM. PMID- 11758241 TI - [Sleep-breathing disordered in stable chronic congestive heart failure]. AB - OBJECTIVE: To determine the prevalence and effect of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure. METHODS: Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography (Polywin 1000, Respironics Inc.). RESULTS: Patients were divided into two groups. Group I (n = 21) had a rate of apnea and hypopnea (apnea-hypopnea index) of 15 or less episodes per hour; group II (n = 15) had a rate of more than 15 episodes per hour. In group II, the rate varied from 16.8 to 78.8 episodes per hour 42.6 +/- 15.5, in which the obstructive apnea hypopnea index was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in group I) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation during sleep [(76.7 +/- 4.6)% compared with (86.5 +/- 2.8)%] and lower left ventricular ejection fraction [(24.2 +/- 8.8)% compared with (31.5 +/- 10.6)%]. CONCLUSIONS: The prevalence of sleep-disordered breathing (mainly periodic respiration or Cheyne-Stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. Severe untreated sleep-disordered breathing may affect left ventricular function and could contribute to death in patients with congestive heart failure. PMID- 11758242 TI - [The role of AT1 receptor and cyclin kinase inhibitor p27 protein in angiotensin II-induced hypertrophy of mesangial cell]. AB - OBJECTIVE: To investigate the role of p27 and AT1 receptor in the hypertrophy of mesangial cell (MC) induced by angiotensin II (Ang II). METHODS: p27 protein of MC lysate was detected with Western blotting analysis. The degree of cultured MC hypertrophy was estimated through [3H] thymidine incorporation and [3H] leucine incorporation. The effect of reducing p27 expression on cell hypertrophy was analysed with p27 antisense oligodeoxynucleotide (ODN) phosphorothioate. The extracellular matrix (ECM) protein (type IV collagen and fibronectin) of MC lysate was examined with ELISA. RESULTS: Ang II stimulated p27 expression of MC cultured in normal glucose DMEM. MC stimulated by Ang II revealed hypertrophy as well as increased [3H] leucine incorporation, decreased [3H] thymidine incorporation and increased ECM. p27 antisense ODN transfection abolished the effect of Ang II mentioned above. Losartan lowered p27 level of MC stimulated by Ang II and attenuated MC hypertrophy induced by Ang II; meanwhile [3H] leucine incorporation and ECM level decreased, [3H] thymidine incorporation increased. The effect of Losartan was dose-dependent. CONCLUSION: Ang II induced MC hypertrophy by increasing p27 protein level through AT1 receptor. Because the cell cycle is controlled by the interplay between the positive and negative cell cycle regulatory proteins (CCRP), further research is needed to study the expression of the positive and negative CCRP in MC in order to understand better the role of CCRP in MC hypertrophy induced by Ang II. PMID- 11758243 TI - [Clinical analysis of tubulointerstitial lesions in IgA nephropathy]. AB - OBJECTIVE: To analyze the characteristics of tubulointerstitial lesions (TIL) in IgA nephropathy (IgAN). METHODS: The pathologic and clinical materials of 609 IgAN patients were analyzed. RESULTS: (1) Prevalence characteristics of TIL: Among all the patients, these with mild TIL accounted for 47.1%, moderate TIL 21.7%, severe TIL was about 16.6% and these without TIL 14.6%. (2) Relationship between TIL and the clinical findings: With increase of the severity of TIL, hypertension became worse and the level of proteinuria increased gradually. On the contrary, serum albumin decreased and renal function degraded. (3) Relationship between TIL and the pathologic findings: With increase of the severity of TIL, the scores of vascular lesion, total glomerular lesion, hypercellularity and glomerulosclerosis increased gradually. Moreover, when the glomerular lesion and vascular lesion became worse, the severity of TIL also increased. The relationship with the crescents was different, the score of the presence of crescents was highest when TIL was moderate in severity; it would not increase when TIL was severe. CONCLUSION: With the increase of the severity of TIL, the condition of IgAN patients became worse. TIL may be one of the key factors for the prognosis of IgAN. TIL is closely related to the severity of glomerular and vascular lesions, and these lesions may further lead to the development of TIL. PMID- 11758244 TI - [The coordinated expression of laminin and its integrin receptor in hepatic sinusoidal capillarization]. AB - OBJECTIVE: To explore the expression of laminin and its integrin receptor alpha 6 in sinusoidal capillaration. METHODS: The rat hepatic fibrosis model was established by injection carbon tetrachloride subcutaneously. Liver sections were examined by scanning electron microscopy and special staining. Then expressions of laminin and integrin alpha 6 subunit were observed by immunohistochemistry and dot immuno-blotting. RESULTS: The pathologic character of hepatic fibrosis sinusoidal capillaration was observed. Sinusoidal capillaration is characterized by defenestration of sinusoidal endothelial cells (SEC) and basement membrane forming and phenotype transformation. By immunohistochemistry staining. The deposition of laminin surrounding sinusoids according to fibrosis stage was 0, 1.92%, 6.02%, 9.68%, 14.14% respectively, statistically different from each other (P < 0.05). In normal rat no expression of integrin alpha 6 were observed in SEC membranes. When capillaration integrin alpha 6 was detected in a continuous pattern along the sinusoidal in accordance with laminin assembly. The content of integrin alpha 6 in fibrotic liver tissues were significantly higher than in normal liver tissues as measured by dot immuno-blotting (P < 0.05). CONCLUSIONS: During fibrogenesis laminin continuously accumulate in liver tissues and form basement membrane resulting in sinusoidal capillaration, meanwhile are company with induced expression of LN-binding-integrin alpha 6 on SEC membranes. These results suggest that coordinated expression of laminin and laminin-binding integrin might be important in pathogenesis of sinusoidal capillaration and hepatic fibrosis. PMID- 11758245 TI - [Dynamic pressure-volume curve predicts the optimal positive end-expiratory pressure in patients with acute respiratory distress syndrome]. AB - OBJECTIVE: To predict the best positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients with dynamic lung pressure-volume (P-V) curve. METHODS: Dynamic and static lung P-V curves were determined in 8 patients with ARDS. The pressure of lower inflection point from dynamic lung P-V curve (Pinfd) was compared with the pressure of lower inflection point from static lung P-V curve (Pinfs). The effect of PEEP on hemodynamics, lung mechanics and gas exchange was observed. RESULTS: When PEEP increased from Pinfd -6 cm H2O to Pinfd +6 cm H2O, partial pressure of arterial oxygen, saturation of arterial oxygen, peak inspiratory pressure and mean airway pressure increased significantly (P < 0.05). Dynamic compliance was improved markedly with PEEP at Pinfd -4 cm H2O when compared with PEEP at Pinfd +6 cm H2O. Cardiac index reduced at Pinf +6 cm H2O. Oxygen delivery was increased at Pinfd -4 cm H2O. When Pinfs and Pinfd were (11.0 +/- 3.2) cm H2O and (12.8 +/- 3.2) cm H2O, they were well correlated (r = 0.99, P < 0.05) and the regression equation was Pinfd = 1.66 + 1.01 x Pinfs. According to the regression equation, it was evident that Pinfd -4 cm H2O equaled to Pinfs -2 cm H2O. CONCLUSION: When ARDS patients are treated with mechanical ventilation, Pinfd -4 cm H2O and Pinfs -2 cm H2O may yield the best PEEP and show maximal oxygen delivery. PMID- 11758246 TI - [The relationship between plasma tumor necrosis factor alpha levels and complications after allogeneic bone marrow transplantation]. AB - OBJECTIVE: To ascertain the implication of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of acute graft-versus-host disease (aGVHD). METHODS: Plasma TNF alpha levels were assessed by ELISA in 243 sera samples from 40 patients who had undergone allogeneic bone marrow transplantation (BMT). Plasma TNF alpha levels were measured before BMT and at different time points after BMT. The results were correlated with aGVHD, infection and conditioning regimen. RESULTS: Plasma TNF alpha levels were significantly higher in patients with grade II and grades III-IV aGVHD (0-4.90) micrograms/L and (0.25-4.21) micrograms/L, respectively than in those with grade 0 or I aGVHD, but there was no clear correlation between plasma TNF alpha levels in patients with grade II and grade III-IV aGVHD. Plasma TNF alpha levels in patients with infection were not statistically different from those in patients without infection. The conditioning regimen did not cause a significant rise in TNF alpha levels. CONCLUSION: It is indicated that TNF alpha may be useful for the diagnosis of aGVHD and for differentiation between aGVHD and other BMT related complications such as infection. PMID- 11758247 TI - [The general level of rheumatology in China should be further improved]. PMID- 11758248 TI - [Application of neuronavigative operation and frameless stereotactic operation in neurosurgery]. PMID- 11758249 TI - [Analysis of inflammation related gene expression spectrum in ankylosing spondylitis patients using cDNA microarray]. AB - OBJECTIVE: To test the difference of gene expression patterns in peripheral blood mononuclear cells (PBMCs) among patients with ankylosing spondylitis (AS) or rheumatoid arthritis (RA) and healthy volunteers and to find potential discriminating genes. METHODS: The PBMC gene expression spectra of 7 patients with active AS, 6 patients with active RA, and 7 healthy volunteers were tested by microarray assay with 588 target gene filters. Semi-quantitative RT-PCR was performed to test the expression rates of thirteen inflammation related genes which had been with high expression rates in at least 4 arthritis patients by microarray assay, among 22 AS patients, 8 RA patients, and 7 healthy volunteers. RESULTS: The expression rates of inflammation related genes by cDNA microarray assay in healthy volunteer group, AS group, and RA group were 8.4%, 32.5% and 44.8% respectively (P < 0.001). The positive rate in RA patients was much higher than that in AS patients (P < 0.012). A significant increase of positive rate of these genes was also noticed in 2 active pulmonary tuberculosis patients. The expression rates of the 13 genes which were positive in at least 4 arthritis patients tested by semiquantitative RT-PCR in 22 AS patients, 8 RA patients and 7 healthy volunteers were very similar to those expression rates tested by cDNA microarray. CONCLUSION: The gene expression profiles of PBMC among AS patients are significantly abnormal and are significantly different from those among RA patients. The high expression of the 13 cytokines is not specific to AS. PMID- 11758250 TI - [In vitro inhibitive effects of Tripterygium wilforii on NO production, iNOS activity, and iNOS-mRNA expression in chondrocyrtes of patients with rheumatoid arthritis]. AB - OBJECTIVE: To study the mechanism of treatment of rheumatoid arthritis with Tripterygium wilfordii Hook. f. (TWHF). METHODS: Chondrocytes from the resected knee joint cartilage of patients with rheumatoid and TWHF, dexamethasone, or (arthritis were isolated and cultured. IL-1 indomethacin of different concentrations were added into the culture solution overnight. Griess reagent was added to the supernatant to detect the content of NO. Chondrocytes were collected to examine the iNOS activity by detecting the conversion of L-14C-arginine into L 14C-citruline. The total RNA of chondrocyte was extracted and the iNOS-mRNA was examined by Northern blotting. RESULTS: The inhibitory rates of NO production by TWHF of concentrations of 2 mg/L, 4 mg/L, 8 mg/L, and 16 mg/L were 10.8%, 25.48%, 55.17%, and 80.45% respectively. The inhibitory rates of iNOS activity by TWHF of concentrations of 2 mg/L, 4 mg/L, 8 mg/L, and 16 mg/L were 12.29%, 27.67%, 59.04%, and 85.06% respectively. Such inhibitory effects were dosage-dependent. TWHF ffectively inhibited the expression of iNOS-mRNA induced by IL-1 in chondrocyte (r = 0.976 and 0.974). Dexamethasone inhibited NO production, iNOS activity, and expression of iNOS-mRNA significantly but not dosage-dependently. Indomethcin only had weak inhibitory effect. CONCLUSION: TWHF inhibits NO production in chondrocytes by limiting the transcription of iNOS gene, which may be one of the mechanisms of treatment of RA with TWHF. PMID- 11758251 TI - [Expression of CCR5 and its ligand in joint fluid and synovium of patients with rheumatoid arthritis]. AB - OBJECTIVE: To investigate the expression and distribution of C-C chemokine recepter 5 (CCR5) and its ligand in peripheral blood, synovium, and synovial fluid so as to study the mechanism of selective accumulation of Th1 cells in rheumatoid joints. METHODS: Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with active rheumatoid arthritis (RA). The expressions of intracellular cytokines, CCR5 and CXCR3 on cytomembraine of SFMCs and PBMCs, and MIP-1 immunofluorescence labelling, and flow cytometry. RESULTS: (1) The selective pattern of intracellular cytokines in SFMCs was drifted towards Th1 subset. (2) The expression rate of CCR5 was 52% Y 8%, the expression rate of CXCR3 was 61% Y 12% in synovial fluid, significantly higher than those of PBMCs. (3) In RA tissues, most of the infiltrating T cells (especially CD4+ T cells), monocyres/microphages, and B cells expressed macrophage inflammatory protein, ligand of CCR5. CONCLUSION: Infiltrating T cells (especially CD4+ T((MIP)-1 cells), monocyres/microphages, and B cells in the synovium of inflammatory, RANTES, and other cytokines which cause the accumulation of CCR5+ Th1 cells. PMID- 11758252 TI - [Clinical evaluation of frameless stereotaxy in minimally invasive neurosurgery]. AB - OBJECTIVE: To evaluate the utility of frameless stereotaxy in minimally invasive neurosurgery. METHODS: A retrospective review of 200 cases of craniotomy and laminotomy procedures using frameless stereotaxy systems performed from December 1999 to June 2001 was made, including 43 cases of AVM, 39 cases of aneurysm, 30 of meningioma, 27 of cavenous malformation, 19 of glioma, 8 of neuronoma, 5 of pituitary tumor, 4 of angioreticuloma, 3 of metastatic tumor, 14 cases of craniotomy with other causes, and 8 spinal tumors. Data of MRI or CT, conducted one day before the operation, were entered into the neuronavigation systems and analyzed. A 3-D simulation of model of cranium or spinal cord was reestablished and operative approach was designed. During the operation, the lesion can be located accurately. RESULTS: The lesions and important anatomical structures were accurately located and the location errors of lesions were within the limit of 2 mm. Postoperative neurological complications occurred only in 10 cases (5.0%). No operative death occurred. CONCLUSION: The frameless stereotaxy is very helpful for brain and spinal surgery, especially for the cases with lesions located deep in the brain. Its accuracy of location is very important in protecting normal brain tissues. The neuronavigation systems are changing the pattern of traditional neurosurgical procedures and serve as the guarantee of minimally invasive neurosurgery. PMID- 11758253 TI - [Percutaneous radiofrequency ablation treatment of hepatocellular cancer]. AB - OBJECTIVE: To evaluate the safety, efficacy and complication of radiofrequency ablation (RFA) in treatment of hepatocellular cancer (HCC). METHODS: 78 HCC patients (58 of Child class A, 14 of Child class B, 6 Child class C) with 110 tumors (with the median diameter of 6.1 cm +/- 2.9 cm and the range of 1.9 to 13.7 cm) were treated by electrodes inserted to the foci percutaneously under ultrasound guidance using RF 2000 generator for 105 times in total (on average for 1.3 times and with 6.3 ablated sessions per patient). After the treatment the patients were followed up for 9.2 months on average (1-16 months). RESULTS: The serum ALT and TBIL were transiently elevated one day after RFA in all patients, and returned to baseline values in 2 weeks. The common response after RFA was mild fever. 6 patients (7.7%) had complications; however, no treatment-related death took place. 43 patients (55.1%) had tumor recurrence 6.1 months after RFA on average. Multivariate analysis demonstrated that the tumor diameter were related significantly to local recurrence (P = 0.0001). There was a significant linear correlation between the number of overlapping ablation sessions and tumor diameter (r = 0.772 16, P = 0.0001) among patients without local recurrence. From further liner regression analysis, a mathematical model: y = -1.794 + 1.733x (P = 0.0001, R-square = 0.5303, y: ablation sessions, x: tumor diameter) was got. CONCLUSION: RFA is a safe and effective nonoperative treatment for HCC. PMID- 11758254 TI - [An application value of detecting K-ras and p53 gene mutation in the stool and pure pancreatic juice for diagnosis of early pancreatic cancer]. AB - OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detecting of K-ras, p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994-2000. 5 and 60-control individuals were enrolled. K-ras point mutations were detected by PCR-RFLP, however p53 mutation was detected by PCR-SSCP. RESULTS: K-ras mutations in pancreatic juice were found in 87.8% (36/41) of pancreatic cancer, 23.5% (4/17) of benign pancreatic disease. Of 261 stools specimens, amplification was successful in 235 (90.0%). K-ras mutation in stool were found in 88.0% (66/75) of pancreatic cancer 51.1% (24/47) of benign pancreatic disease, 19.6% (9/46) of normal individuals. p53 mutation in pancreatic juice were found in 47.4% (18/38), 12.5% (2/16) of benign pancreatic disease, p53 mutation in stool were found in 37.1% (23/62), 19.1% (4/12) of chronic pancreatitis. CONCLUSION: K-ras mutation in pancreatic juice has high sensitivity and specificity, so it can be used as a adjunct in the diagnosis of pancreatic cancer. Detection of K-ras mutation combined with p53 mutation in stool can be helpful to screen for pancreatic carcinoma. Combined with serum CA19 9 detection, it might increase the early diagnostic rate of pancreatic carcinoma. PMID- 11758255 TI - [Surgical treatment of elderly patients with pancreatic neoplasm]. AB - OBJECTIVE: To further elucidate the clinical feature, treatment and prognosis of pancreatic cancer in elderly patients. METHODS: Data of 180 elderly patients with pancreatic cancer operated upon during 1990-2000 were analyzed. Postoperative complications and 30-day mortality rates were recorded among the 46 cases subjective to Whipple procedure, including 22 cases undergoing regional pancreatoduodenectomy after intervention therapy. 78 patients received palliative surgery and 50 patients received laparotomy. Follow-up was made for 6 months to 10 years. RESULTS: All the patients were operated upon successfully. 48 patients underwent radical pancreatectomy with a mortality rate of 6.2 per cent, a complication rate of 20.8 per cent, and a mean survival period of 26 months. The 78 cases undergoing palliative surgery survived for 6 months on average. 54 patients undergoing laparotomy only survived for 3 months on average. CONCLUSION: Aggressive surgical management helps prolong the survival period and improve the life quality of elderly patients with pancreatic cancer. PMID- 11758256 TI - [Characteristics of malignant clone from acute lymphocytic leukemia]. AB - OBJECTIVE: To identify the characteristics of malignant clones in leukemia. METHODS: VH region of B lymphocytes from children with ALL, patients with MM, and tissues from fetuses obtained by induced labor at different gestational stages was amplified using RT-PCR method with one primer located in VH1, VH2, VH3, VH4, VH5, or VH6 and another primer at the join region. The PCR products were then separated on sequencing gel and their VH gene fingerprints were obtained. The fingerprints from tissues of fetal liver, spleen, thymus and bone marrow, and bone marrow B cell from 15 cases of ALL and one case of MM were compared, and VH repertoire information were deduced from those fingerprints. RESULTS: The VH6 family was the dominant family in fetal liver and the VH3 family occurred predominantly in fetal spleen and bone marrow. Monoclonal proliferation of B lymphocytes was found in 9 of the 15 patients with ALL. Of these 9 cases, proliferation of VH1 was found in 3 cases, proliferation of VH6 was found in 3 cases, and proliferation of both VH3 and VH4 in 2 cases. The VH families other than leukemic clone(s) in these patients were in normal distribution or suppression status. Oligoclonality was found in one ALL case with malignant growth of VH1, VH3 and VH6. Polyclonality with nearly normal spectrum of VH1-VH6 was detected in 6 of the 15 cases. DNA sequencing of a VH3 clone from an ALL case demonstrated a similarity to the sequence of embryonic clone from a fetus of gestational age of 13 weeks. The VH sequence of one adult MM case, with hypermutation of somatic cell, was remarkably different from that of the germline. CONCLUSION: Rearrangement of VH1, VH3, VH4 and VH6 can be frequently found in ALL. It is unlikely that leukemia in childhood originates from stimulation of foreign antigens. PMID- 11758257 TI - [Defective expression of B7.2 in B cell chronic lymphocytic leukemia B cells]. AB - OBJECTIVE: To investigate the expression of B7.1 and B7.2 molecules in peripheral B cells of patients with chronic B cell lymphocytic leukemia (BCLL) and to study the relationship between B7.1 and B7.2 expression and pathogenic mechanism of BCLL. METHODS: Peripheral blood mononuclear cells (PBMC) were separated by Ficoll Hypaque lymphocytes separation medium from 25 normal persons (normal control group) and 23 BCLL patients (BCLL group) which were further divided into two groups, phase 0-II group and phase III-IV group. Flow cytometry (FCM) was used to analyze the B7.1 and B7.2 expression in peripheral B cells after the mononuclear cells had been cultured for 24 hours in vitro. RESULTS: The B7.2 expression in B cells of BCLL patients was significantly lower than that in normal control group (P < 0.05). No statistically significant difference was found in the B7.1 expression and co-expression of B7.1 and B7.2 between the BCLL group and normal control group. The average B7.2 expression rates in patients of phase 0-II group and phase III-IV group were 25% +/- 17% and 17% +/- 8% respectively without statistically significant difference. CONCLUSION: The B7.2 expression in B cell of patients with BCLL is defective, which may be one of the pathogenic mechanisms of chronic BCLL and a major cause why the body fails to clear the BCLL cells via immunological means. PMID- 11758258 TI - [The change of human Na+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with pathogenesis of nephrolithiasis]. AB - OBJECTIVE: To study the change of Na+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with nephrolithiasis. METHODS: 50 volunteers and 85 patients with nephrolithiasis were divided into 3 groups: control, nephrolithiasis with normal urine citrate, and nephrolithiasis with hypocitraturia. The expression of hNaDC1 mRNA in kidney was determined by RT-PCR or Northern blotting, the change of hNaDC1 protein abundance were measured by immunohistochemical staining with anti-hNaDC1 antibody among part of these patients and volunteers. The plasma and urinary biochemical parameters, such as citrate, oxalate, uric acid and calcium etc., were analyzed by routine chemical methods. RESULTS: The recurrence rate of nephrolithiasis in the group of patients with hypocitraturia was 36.1%, significantly higher than the recurrence rate of 16.3% in the group of patients with normal urine citrate (P < 0.01). hNaDC1 was expressed in the normal kidney, localized in the striated border of renal proximal tubule. However, it was expressed highly in the kidneys of patients with hypocitraturia. The ratio hNaDC1 mRNA/18sRNA in the patients with hypocitraturia was 0.65 +/- 0.21, significantly higher than that in the controls (0.36 +/- 0.11, P < 0.01). The ratio hNaDC1 mRNA/18sRNA in the patients with normal urine citrate was not significantly different from that in the controls (P > 0.05). The urine pH and urine sodium were significantly lower in the patients with hypocitraturia than in the other two groups. The levels of urine calcium and urine oxalate were significantly higher in the patients with hypocitraturia than in the controls, and were not different from those in the patients with normal urine citrate. CONCLUSION: The upregulation of hNaDC1 mRNA and protein abundance in the kidney may be an important cause of hypocitraturia, which might be related with the occurrence and recurrence of nephrolithiasis. PMID- 11758259 TI - [Experimental study of in osteogenesis in duced by NIH-3T3 cells transfected with bone morphogenetic protein 3 gene]. AB - OBJECTIVE: To investigate the gene expression, protein synthesis and inducing osteogenetic capacity of NIH-3T3 cells transfected with recombinant human bone morphogenetic protein 3 (rhBMP3) gene. METHODS: Gene recombination technique was used to clone the BMP3 cDNA into PcDNA3 vector directly, and to form a recombined BMP3-PcDNA3 cDNA, which was introduced into NIH-3T3 cells by means of lipofectamine transfer. The total RNA of transfected NIH-3T3 cells was then extracted to verify the mRNA expression of BMP3 using Northern blot method. BMP3 protein synthesis and AKP activity in the transfected cells was checked. Then, the NIH-3T3 cells transfected with BMP3 gene were injected into nude mouse muscle to evaluate the inducing osteogenesis in the muscle. RESULTS: BMP3 gene had been inserted into PcDNA3 vector successfully. There was BMP3 mRNA expression in the total RNA of NIH-3T3 cells with the peak level appearing in the 6th week after transfection, and BMP3 protein was found in NIH-3T3 cells, and the AKP level is much higher in the transfected NIH-3T3 cells than in non-transfected NIH-3T3 cells. Histologic examination revealed that there were a large number of chondrocytes and trabeculae seen in the nude mouse muscle 4 weeks after injection of the transfected NIH-3T3 cells. CONCLUSION: BMP3 is a protein that possesses osteogenetic effect. After transfection with BMP3-PCDNA3, BMP3 mRNA expression and protein formation can be found in NIH-3T3 cells, and the transfected NIH-3T3 cells have the effect of inducing osteogenesis in vivo. PMID- 11758260 TI - [Experimental research of host endothelialization of transplanted hetero-heart valve by transfer of VEGF gene]. AB - OBJECTIVE: To investigate the feasibility of host endothelialization of transplanted hetero-heart valve by transfer of VEGF gene. METHODS: Bovine pericardium treated with glutaraldehyde and L-glutamine was positioned into ping's right atrium, then gene suture carrying plasmids with pcD2/hVEGF121 gene or only with pcD2 was sewn into the anterior wall of right ventricle. The contents of VEGF protein in blood from right atrium and peripheral vein were determined by ELISA 10 days after the transplantation. The expression of VFGF mRNA in the myocardium near the gene suture was detected by RT-PCR 16 days after the transplantatipn. Microscopy and unltrastructural analysis of the transplanted valve were carried out. RESULTS: The content of VEGF protein in blood from the right atrium in the pcD2/hVEGF121 group was significantly higher than that in the pcD2 group 10 days after the VEGF gene transfer (P < 0.01). The expression of VEGF mRNA in the myocardium of right ventricle in pcD2/VEGF121 group was much higher than that in the left ventricle of the same group and that in the right ventricle in pcD2 group. Morphological observation showed that the coverage rate of host endothelium in pcD2/hVEGF121 group was higher than in pcD2 group 16 days after the gene transfer (P < 0.05). 30 days after the gene transfer. Complete host endothelialization was observed 30 days after the operation. CONCLUSION: VEGF gene transfer with surgical suture promotes the host endothelialization of bioprothesis, thus inhibiting calcification of biological valves and improving biocompatibility and long-term durability of bioprothesis. PMID- 11758261 TI - Didactic components of a comprehensive pediatric competency program. AB - The infusion nurse specialist working with pediatric patients must demonstrate competencies related to all stages of child growth and development. In addition, specific skills requiring competency validation in the pediatric practice setting include calculation of pediatric dosages, maintaining fluid balance, use of specific devices, age-specific skills, and management of complications. This article presents a discussion of each of these areas as well as recommendations for methods of competency validation. PMID- 11758262 TI - Litigation risks for infusion specialists. Understanding the issues. AB - The legal aspects of caring for patients and the fear of disciplinary actions or malpractice suits understandably are matters of great concern for infusion specialists. This article is intended to be a broad overview of some of the legal causes of action that may arise through the rendering of professional nursing care, as well as an introduction to patients' rights to self-determination, informed consent, and informed refusal as a special area of litigation risk for the infusion specialist. PMID- 11758263 TI - Maintaining infusion therapy services in the long-term care setting. AB - The volume of infusion therapy services provided in the long-term care setting has declined. One major influence has been the changes in reimbursement experienced in this sector of the industry. This article is intended to stimulate the long-term care clinician to reexamine the service offered and to be creative in his or her approach to building infusion services. The article also explores parallels to the home infusion industry, which has evolved through similar changes, with the intent of learning from its experiences. PMID- 11758264 TI - A model for home infusion therapy initiation and maintenance. AB - Many factors impact the success of home infusion therapy. A model has been designed to incorporate all of the factors that need to be considered when setting up a home infusion program. The primary factors included in the model are patient, nursing, medical, caregiver, equipment, environment, medication, and legal issues. Each of the factors are subdivided into relevant points to be included in the patient's discharge management plan. Using the model will help nurses make a comprehensive patient assessment, plan patient and caregiver education, and assist patients in completing their course of infusion therapy. PMID- 11758265 TI - Safety and efficacy of an improved antiseptic catheter impregnated intraluminally with chlorhexidine. AB - The safety and efficacy of a second-generation improved antiseptic catheter impregnated with silver sulfadiazine and increased levels of chlorhexidine on its outer surface and chlorhexidine alone on its luminal surfaces was compared in vitro and in vivo to standard antiseptic catheters impregnated with these antimicrobials on their outer surfaces only. In rat and pig intravenous models, the improved antiseptic catheter was significantly more effective in resisting both outer surface and luminal colonization compared with the standard antiseptic or control catheters. There was no evidence of tissue toxicity in any group. PMID- 11758266 TI - Local anesthesia prior to the insertion of peripherally inserted central catheters. AB - Using a randomized, controlled study, the investigators evaluated and compared the effects of local anesthesia versus no anesthesia on pain associated with peripherally inserted central catheter (PICC) insertion. A sample of 42 subjects was selected and divided into three groups. Group 1 received EMLA cream. Group 2 received buffered lidocaine. Group 3 (the control group) did not receive a local anesthetic. The short form of the McGill Pain Questionnaire was used to measure pain quality and intensity. A numerical Visual Analogue Scale accompanied the questionnaire and measured overall pain intensity. Results showed that buffered lidocaine was statistically superior to EMLA cream or no anesthetic in relieving pain associated with PICC insertion. PMID- 11758267 TI - [Pesticide poisoning referred to the Poison Center of Milan in 1995-1998]. AB - From 1995 through 1998 the Poison Control Centre of Milan identified 7594 cases of suspected or confirmed cases of acute pesticide poisoning. Domestic use products accounted for 4483 (59%) of the cases. Of these, 84% occurred at home and 48% in children under five. The most frequently reported domestic use products were pyrethrins/pyrethroids (26%), fertilizers (19%) and camphor/naphthalene (12%). Of 3111 cases (41%) due to agricultural products, 10% were children under five and 69% were males. Half of the poisonings from agricultural products occurred at home, the remainder at workplace. The products most frequently reported were organophosphates (26%), pyrethrins/pyrethroids (9%), and carbamates (9%). These preliminary data indicate the importance of implementing prevention programs to reduce pesticide poisonings with particular reference to young children. PMID- 11758268 TI - [Consultations at the Poison Center of Rome on pesticide poisoning referrals]. AB - From 1 January 1998 to 31 October 1999 the two Poison Control Centres active in Rome provided 923 telephone consultations for individuals and health care providers on suspected poisonings involving pesticides. Exposures more frequently reported in association with suspected cases were insecticides (n. 636), including organophosphates (n. 300), carbamates (n. 155), pyrethroids (n. 102), and organochlorines (n. 79). Children aged 1-4 years accounted for 22% of all suspected poisonings (n. 200). Each case was classified as to the likelihood of a relationship between the reported pesticide exposure and the occurrence of health effects. Around 18% of suspected pesticide poisonings (n. 168) were subsequently classified as definite, around 43% (n. 390) as possible, and around 37% were considered unlikely (n. 344). PMID- 11758269 TI - [Pesticide poisonings compensated by the INAIL in 1995-98]. AB - The present paper describes agricultural pesticide-related accidents compensated by the Italian national institute for insurance of occupational accidents (INAIL) from January 1995 to December 1998. During the period under study, 643 accidents claims were examined by INAIL and 549 received compensation. The Italian regions with the highest number of compensation during the period under study were Puglia (no. 102), Sicily (no. 66), Emilia-Romagna (no. 61), and Veneto (no. 55). The national annual rate of pesticide-related accidents, estimated by dividing the number of cases receiving compensation by the number of insured agricultural workers was 12 per 100,000 per year. The regions with the highest rates were Puglia and Marche (27 per 100,000 per year), Liguria (22 per 100,000 per year), and Sicily (18 per 100,000 per year). Most of the cases (70%) occurred among male workers. The agents most frequently reported to have caused the accidents were fungicides (32.2%). For a relevant number of cases (34.2%) the exposure was not specified. PMID- 11758270 TI - [Acute poisoning with methomyl and other pesticides in the province of Ragusa, Sicily]. AB - In 1995-96, the Occupational Medicine Service of the province of Ragusa, Sicily, examined all cases of pesticide poisonings among persons seen in two local emergency departments, identifying 86 cases due to unintentional pesticide exposure. Methomyl, a highly toxic carbamate, was indicated for 51% of all cases. The most frequently reported symptoms included nausea and vomiting (48%), excessive perspiration (33%), and dyspnea (16%). Fifty-nine cases (69%) were hospitalized, 5 in intensive care. The methomyl cases occurred more frequently during summer months while the cases from all other pesticides showed no seasonal patterns. These observations point out the relevance of identifying acute pesticide poisonings in the province of Ragusa and suggest that ongoing registration of these events should be a public health priority. PMID- 11758271 TI - [The problem of the presence of dangerous adjuvants in pesticide preparations used in agriculture or households]. AB - Problems related to the presence of dangerous co-formulating agents and adjuvants in plant protection products and biocides are described. Usually, these kind of preparations are made including big quantities of different inerts (solvents, adhesives, wetting agents, surfactants, etc.), often more dangerous than the active ingredients. The obligatory declaration on the label about identity and concentration of some of these substances is not provided by the actual legislation. Sometimes, as in the case of accidental poisoning, the real nature of the toxicological damage is difficult to recognize. Also for the environmental compartment, the persistence of some preparation can be hugely increased by the presence of inerts added on purpose for lasting the efficacy. PMID- 11758272 TI - [Health costs of acute poisoning with pesticides: empirical analysis]. AB - This work, based on an empirical analysis carried out by the Poison Centre of Milan, is an attempt to estimate the direct costs of acute intoxication due to pesticide use in Italy. From the analysis undertaken, it is possible to demonstrate that the number of incidents of acute intoxication registered every year in Italy is not negligible and that it causes a cost of nearly Lit 2,000,000,000. The investigation, supported also by empirical studies from other countries, suggests that, in order to reduce the incidence of this pathology, greater attention should be paid to prevention, regulation and education. PMID- 11758273 TI - [Biologic monitoring of occupational and non-occupational exposure to pesticides]. AB - Occupationally or otherwise, much of the population is exposed to pesticides. To obtain information on exposure levels, biological monitoring is often the best choice because it provides data that reflects total exposure by all routes. Biological monitoring has been used to evaluate exposure in agricultural and industrial environments, in subjects poisoned by accidental or voluntary contact, in volunteers for pharmacokinetic studies and in the general population. This paper is based on 100 studies published on this topic and reviews exposure indices for the main classes of pesticides. Methods of sampling and conservation of samples are outlined, together with the analytical procedures used. For compounds such as organophosphate and pyrethroid insecticides, ethylenebisdithiocarbamate fungicides, and phenoxyacetic herbicides, the results of studies on the general population and groups of occupationally exposed workers are reported. PMID- 11758274 TI - Surveillance of acute occupational pesticide-related illness and injury: the US experience. AB - In the United States there are numerous state-based and national surveillance systems that collect data on acute pesticide-related illnesses and injuries. On the state level, Arizona, California, Florida, Louisiana, New York, Oregon, Texas, and Washington routinely collect illness data due to pesticide exposure and conduct comprehensive case investigations. On the national level, the American Association of Poison Control Centers coordinates the Toxic Exposure Surveillance System, and the Bureau of Labor Statistics provides annual estimates of the number of occupational pesticide-related illnesses and injuries that result in days away from work. The various systems are described and compared, and examples are provided of prevention measures that have been implemented as a result of surveillance activities. PMID- 11758275 TI - [National surveillance system for acute poisoning caused by pesticides]. AB - In the present paper is presented the surveillance system for pesticide-related illnesses proposed by the Istituto Superiore di Sanita, in collaboration with the Ministry of Health. Through the collaboration of local or regional poison control centres and local health departments with public hospitals and emergency departments, cases of acute pesticide-related illnesses among persons seeking health care will be registered according to standard procedures. Data collected locally will be transmitted to the Istituto Superiore di Sanita for registration and evaluation of the association between symptoms and type of exposure and for severity of illnesses related to pesticide exposure. These data will be analysed at regular intervals in order to estimate the magnitude of the problem of acute pesticide-related illnesses in Italy and to identify priority areas for implementing public health prevention and intervention programs. PMID- 11758276 TI - On the social responsibility of scientists. AB - The author outlines the history of genetics in the United States, looking at all the social and political implications of it, too often underestimated by the geneticists themselves. In contrast to physicists, who were forced to recognize the consequences of their role in the development of the atomic bomb and who openly carried a historical burden from their past, geneticists had no historical memory and were essentially ignorant of their own "atomic" history: the Eugenics movement in the first half of 20th century, which significantly affected social policy in the United State and Europe. Few geneticists, in fact, until recently, were aware of the Eugenics movement itself. It was only with the extreme misuse of genetics by German scientists and the Nazi Government that some English and US geneticists began to speak out more openly. The author sees in this lack of awareness the major responsibility of geneticists for the misrepresentation and misuse of science and also calls for a better interaction between scientists and those who work in other social fields; a communication gap between the two cultures holds dangers for us all. PMID- 11758277 TI - [Guidelines given by several international documents to the Italian legislation on bioethics in scientific research]. AB - Moving from the most recent progresses in some address international acts on bioethics of the research, the Convention of human rights and biomedicine and La declaration universelle sur le genome humain e les droits de l'homme, this paper describes the legislative acts which regard many aspects of theoretical and practical scientific research, both in the Italian national and supra-national fields. This legislation concerns mainly the following topics: rights of the human subjects of research, informed consent, privacy on the personal data, activity on organ transplantation, research in genetics, activity in the field of treatment of human gametes and embrios. The author here quotes these legislative acts referring briefly to national and international laws. PMID- 11758278 TI - [Personal computer interactive algorithm for estimating radiologic contamination and doses after a nuclear accident in Europe]. AB - The algorithm RANA (radiological assessment of nuclear accidents) is a tool which can be exploited to estimate the space and time structure of the radiological consequences of a radioactive release following a nuclear accident in Europe. The algorithm, formulated in the language of Mathematica, can be run on a personal computer. It uses simplified physical assumptions as for the the diffusion of the cloud and the transfer of the contamination to the food chain. The user gets the needed information by means of interactive windows that allow a fast evaluation of dose and contamination profiles. Calculations are performed either starting from the source terms or from the knowledge of experimental contamination data. Radiological consequences, such as individual or collective doses from several exposure paths, are parametrized in terms of the atmospheric diffusion categories. PMID- 11758279 TI - [Infantile leukemia and exposure to 50/60 Hz magnetic fields: review of epidemiologic evidence in 2000]. AB - We review the epidemiological evidence on childhood leukemia and residential exposure to 50/60 Hz magnetic fields. The possibility of carcinogenic effects of power frequency magnetic fields (ELF-EMF), at levels below units of micro tesla (microT), was first raised in 1979 by a case-control study on childhood cancer carried out in Denver, USA. In that study, excess risks of total cancer and leukemia were observed among children living in homes with "high or very high current configuration", as categorised on the basis of proximity to electric lines and transformers. Many other epidemiological studies have been published since then, characterised by improved--although still not optimal--methods of exposure assessment. At the end of 2000, the epidemiological evidence to support the association between exposure to extremely-low-frequency magnetic fields and the risk of childhood leukemia is less consistent than what was observed in the mid 90s. At the same time, a growing body of experimental evidence has accumulated against both a direct and a promoting carcinogenic effect of ELF-EMF. Such "negative" experimental evidence hampers a causal interpretation of the "positive" epidemiological studies. PMID- 11758280 TI - Optimization of intensity modulated radiation therapy: assessing the complexity of the problem. AB - Intensity modulated radiation therapy (IMRT) is one of the most innovative techniques in oncological radiotherapy, allowing to conform the dose delivery to the tumoral target, preserving the normal tissue. The high number of parameters involved in the IMRT treatment planning requires an automated approach to the beam modulation. Such optimization process consists in the search of the global minimum of a cost function representing a quality index for the treatment. The complexity of this task, has been analyzed with a statistical approach for three clinical cases of particular interest in IMRT. Our main result is that a cost function based on dose-volume constraints entails lower complexity of the optimization process, in terms of the choice of the parameters defining the cost function and in a smaller sensitivity to the initial conditions for the optimization algorithm. PMID- 11758281 TI - Implementation of neuromorphic systems: from discrete components to analog VLSI chips (testing and communication issues). AB - We review a series of implementations of electronic devices aiming at imitating to some extent structure and function of simple neural systems, with particular emphasis on communication issues. We first provide a short overview of general features of such "neuromorphic" devices and the implications of setting up "tests" for them. We then review the developments directly related to our work at the Istituto Superiore di Sanita (ISS): a pilot electronic neural network implementing a simple classifier, autonomously developing internal representations of incoming stimuli; an output network, collecting information from the previous classifier and extracting the relevant part to be forwarded to the observer; an analog, VLSI (very large scale integration) neural chip implementing a recurrent network of spiking neurons and plastic synapses, and the test setup for it; a board designed to interface the standard PCI (peripheral component interconnect) bus of a PC with a special purpose, asynchronous bus for communication among neuromorphic chips; a short and preliminary account of an application-oriented device, taking advantage of the above communication infrastructure. PMID- 11758282 TI - [Aedes albopictus in Italy: an underestimated health problem]. AB - Since 1990, Ae. albopictus has spread in 9 regions and 30 provinces of the country. This species was introduced in Italy in shipments of scrap tires form the USA. In Italy, Ae. albopictus is the major biting pest throughout much of its range and, although there is no evidence that this mosquito is the vector of human disease in the country, the species might be involved in the transmission of some arboviruses which have been reported in the Mediterranean Basin. Aim of this paper is to provide an update on the distribution of Ae. albopictus in Italy and to renew the interest in a problem frequently underestimated. Public health implications after a ten-year presence of the species are also discussed. PMID- 11758283 TI - [Aedes albopictus in Rome: monitoring in the 3-year period of 1998-2000]. AB - Aedes albopictus was first reported in Italy in 1990 and in the urban area of Rome in the late summer 1997. Ae. albopictus is a daytime, outdoor mosquito, that bite preferably on man. In Rome (42 degrees South of latitude), larvae are found from March to November, but some adult females are active until December. The peak of adult abundance, and then of the annoyance caused to man, occurs in late August-September. The presence of the species in Rome represents the first example in Italy of extensive colonization of an urban area, with involvement of hundred-thousand people. Since 1997, Ae. albopictus has spread quickly from the initial foci to the whole city. In 2000, scattered foci of the species have been reported throughout the urban area and in some towns of the province. PMID- 11758284 TI - [Recent findings on the treatment of leishmaniasis]. AB - The increased interest in leishmaniasis is due to the importance of travel medicine and the demonstration of Leishmania as an opportunist agent in immunosuppressed individuals, besides the persistence of traditional endemic foci. During the past ten years there have been important developments in therapy, which include: a) new dosages/combinations of old drugs, resulted from controlled clinical trials; b) new formulations, which have increased the bioavailability and decreased the toxicity of traditional drugs; c) new molecules, developed for other diseases but found effective against Leishmania. However, while it is now possible to cure severe forms of leishmaniasis with 3-5 infusions of new-generation drugs, the prohibitive costs will preclude the access of developing countries to new therapies. PMID- 11758285 TI - [Bacterial symbionts (Wolbachia) of filarial nematodes: implications for the treatment and pathology of filariasis]. AB - Filarial nematodes harbour intracellular, Gram-negative bacteria belonging to the genus Wolbachia. These bacteria have been observed in various species of filariae, including the main filariasis agents of humans and animals. It has been suggested that Wolbachia could play an important role in the biology of filarial nematodes and could be implicated in the pathogenesis of filarial diseases. Wolbachia could thus represent a target for the control of filariasis and key to the understanding of these diseases. Indeed, in various species of filariae, tetracycline treatments have been shown both to reduce/eliminate the Wolbachia population and to determine detrimental effects on the nematodes. In addition, proteins of Wolbachia have been shown to determine specific IgG responses in animals infected by filariae and some Wolbachia molecules (e.g. LPS) have been shown to stimulate innate-immunity responses (e.g. production of cytokines such as IL1, IL6, IL10, TNF-alpha and IFN-gamma by macrophages). PMID- 11758286 TI - [Information in the fight against HIV infection and AIDS: results of a knowledge survey among general practice physicians, journalists, and users of the AIDS Green Line]. AB - This work presents the outcomes of the study "Evaluation of the role of social communication in the fight against HIV infection and AIDS" carried out by some researchers of the Istituto Superiore di Sanita (ISS) and financed within the 2nd Social Research Project on AIDS. Through an accurate survey, the study aimed to evaluate the standard of knowledge on HIV/AIDS in two most important sources of information frequently contacted by citizens: general practitioners and journalists. It also sounded out the knowledge in a random sample of users of the AIDS Help-Line of the ISS. We could find out a generally low standard of knowledge of HIV/AIDS among journalists. As far as general practitioners are concerned, the differences found in the standard of knowledge are inversely proportioned to age and number of patients. A fairly good standard of knowledge is found out among the users the AIDS Help-Line. Of course, the same outcomes cannot be valid also for the general population; on the contrary, the outcomes concerning general practitioners and journalists could be generalized. Information gathered from data collection could make easier the planning of more specific interventions and the drawing up of appropriate guidelines. PMID- 11758287 TI - The DAI prospective study on macrovascular complications in patients with type 2 diabetes. Characteristics of the study population. AB - A large multicenter cohort study, the DAI study, is being performed on patients with type 2 diabetes mellitus who are followed by diabetic care units in Italy, to study the prevalence and incidence of myocardial infarction, ischemic heart disease, coronary artery bypass, coronary angioplasty, cerebral thromboembolism, and amputations. The reference population consists of all patients visited at the participating units in the period September-December 1998 or March-June 1999. Patients were randomly chosen so as to create a sample representative of the diabetic population visited at the units. Overall, 201 of the approximately 650 Italian diabetic care units participated in the study and 24,094 patients were included in the study. The paper presents the protocol and the characteristics of the DAI study population. PMID- 11758288 TI - [Determination of 4-bromo-2,5-dimethoxyamphetamine (DOB) found in illicit tablets seized in Italy]. AB - Some of the molecules belonging to the amphetamines group (4-bromo-2,5 dimethoxyamphetamine, DOB) or to the phenethylamines (4-bromo-2,5-dimethoxy phenethylamine, 2C-B or Nexus) have closely related structures that make their identification quite difficult. The unambiguous identification is crucial in forensic responses. This paper describes the analytical approach used to achieve the identification of the main ingredient contained in tablets seized in the illicit market of Rome (Italy) and submitted to our laboratory by the Court of Law of Rome. The procedure entails the basic extraction of the main ingredient from the tablets with tert-butyl methyl ether followed by qualitative gas chromatographic mass-spectrometric (GC-MS) analysis using both electron impact detection (EI) and chemical ionization (CI). The examination of the mass spectra obtained from the native molecule and from its pentafluoropropionyl-derivative allows the structural identification of the side chain and the substitutions on the aromatic ring. This analytical approach can thus be useful to distinguish between amphetamine-like and phenetylamine-like compounds using instruments and techniques commonly available in the forensic toxicology laboratories. PMID- 11758289 TI - [Review of significant studies on monomer vinyl chloride produced in municipal waste landfill plants]. AB - It is known that presently in Italy about 78% of generated urban waste solids get deposited in waste dumpsites. As of today, there is little known knowledge regarding the quality of the ambient surrounding dumpsites. Therefore it has become extremely important to understand the "risk factors" associated with a dumpsite. Through recent studies carried out mostly in the USA, there is evidence of widespread presence of vinyl chloride monomer (VCM) in the environment in proximity of industrial as well as urban dumpsites. The following is a summary of the most significant study reports with respect to the above. From an estimate based on study results, it is estimated that waste dumpsites in the USA emit altogether between 60 and 33,000 tons/year of vinyl chloride monomer into the atmosphere and ground water. Consequently these studies have shown the necessity to include vinyl chloride monomer amongst the monitoring parameters at waste dumpsites both during the operational phase, as well as during the post mortem phase. PMID- 11758290 TI - Reviewing the reviews. How strong is the evidence? How clear are the conclusions? AB - OBJECTIVES: The objectives of this paper were: a) to determine what can be learned from conclusions of systematic reviews about the evidence base of medicine; and b) to determine whether two readers draw similar conclusions from the same review, and whether these match the authors' conclusions. METHODS: Three methodologists (two per review) rated 160 Cochrane systematic reviews (issue 1, 1998) using pre-established conclusion categories. Disagreements were resolved by discussion to arrive at a consensual score for each review. Reviews' authors were asked to use the same categories to designate the intended conclusion. Interrater agreements were calculated. RESULTS: Interrater agreement between two readers was 0.68 and 0.72, and between readers and authors, 0.32. The largest categories assigned by methodologists were "positive effect" (22.5%), "insufficient evidence" (21.3%), and "evidence of no effect" (20.0%). The largest categories assigned by authors were "insufficient evidence" (32.4%), "possibly positive" (28.6%), and "positive effect" (26.7%). CONCLUSIONS: The number of reviews indicating that the modern biomedical interventions show either no effect or insufficient evidence is surprisingly high. Interrater disagreements suggest a surprising degree of subjective interpretation involved in systematic reviews. Where patterns of disagreement emerged between authors and readers, authors tended to be more optimistic in their conclusions than the readers. Policy implications are discussed. PMID- 11758291 TI - Factors of the innovation, organization, environment, and individual that predict the influence five systematic reviews had on public health decisions. AB - OBJECTIVE: To determine the extent to which systematic reviews of public health interventions influenced public health decisions and which factors were associated with influencing these decisions. METHODS: This cross-sectional follow up survey evaluated the use of five systematic reviews in public health decision making. Independent variables included characteristics of the innovation, organization, environment, and individual. Primary data were collected using a telephone survey and a self-administered organizational demographics questionnaire. Public health decision makers in all 41 public health units in Ontario were invited to participate in the study. Multiple linear regression analyses on the five program decisions were conducted. RESULTS: The systematic reviews were perceived as having the greatest amount of influence on decisions related to program justification and program planning, and the least influence on program evaluation decisions. The greater the perception that one's organization valued the use of research evidence for decision making and that ongoing training in the critical appraisal of research literature was provided, the greater the perception of the influence the systematic review had on public health decisions. CONCLUSIONS: Organizational characteristics are important predictors of the use of systematic reviews in public health decision making. Future dissemination strategies need to promote the value of using systematic reviews for program decision making as well as promote ongoing training in critical appraisal among intended users in Ontario. PMID- 11758292 TI - Reproducibility and responsiveness of evaluative outcome measures. Theoretical considerations illustrated by an empirical example. AB - OBJECTIVE: This article outlines basic methods for quantifying reproducibility and responsiveness of evaluative outcome measures. METHODS: The background noise in stable patients provides the desired information to quantify the reproducibility. From this, the smallest real difference (SRD) for longitudinal differences can be derived. We propose to use the SRD to define responsiveness: from all patients who change according to an external criterion, we take the percentage that changes at least SRD on the outcome measure. A more complete picture of the responsiveness of the outcome measure arises when the receiver operating characteristic (ROC) is constructed, corresponding to all possible cut off change scores. The proposed methods are illustrated with an empirical example. RESULTS: In the illustration the methods appeared to be very useful and complemented each other. We could evaluate whether the observed change score was larger than that expected due to chance. With the methods it was possible to evaluate both the ability of an instrument to detect change if there is a real change in health status (sensitivity to change) and the ability to detect absence of change if there is no real change (specificity to change). CONCLUSION: We presented the use of SRDs and ROC curves for quantifying reproducibility and responsiveness. We started with the basic notions and arrived at methods that are both understandable and useful. PMID- 11758293 TI - A fallacy of the multiplicative QALY model for low-quality weights in students and patients judging hypothetical health states. AB - OBJECTIVES: In quality-adjusted life-years (QALY) models, it is customary to weigh life-years with quality of life via multiplication. As a consequence, for positive health states a longer duration has more QALYs than a shorter duration (i.e., longer is better). However, we have found that for poor health states, many prefer to live only a limited amount of time (i.e., longer is worse). Such preferences are said to be maximum endurable time (MET). In the present contribution, the following questions are asked: a) How low does the utility have to be in order for a MET to arise? and b) Do MET preferences occur when patients judge hypothetical health states? METHODS AND RESULTS: We reanalyzed data from 176 students for the hypothetical health states of "living with migraines" and "living with metastasized cancer." For utilities smaller than 0.7 (ranging from 0 to 1), the MET preference rate was larger than 50%. High MET preference rates were also found in two new studies on migraine and esophageal cancer patients, who evaluated hypothetical health states related to their disease. CONCLUSIONS: We discuss the interpretation of the MET preferences and the preference reversal phenomenon. Standard QALY models imply that longer is better. However, we find that more often, longer is worse for poorly evaluated health states. Consider the following question: are 3 years with a weight of 0.3 equally as valuable as 1 year with a weight of 0.9? Our results suggest that the 3-year period may be less valuable because for poor health, many will prefer a 1-year over a 3-year period. PMID- 11758294 TI - Cost-effectiveness analysis of laparoscopic versus minilaparotomy cholecystectomy for gallstone disease. A randomized trial. AB - OBJECTIVE: To evaluate the total cost of minilaparotomy cholecystectomy (MC) and laparoscopic cholecystectomy (LC) and perform a cost-effectiveness (CE) analysis. METHODS: One hundred adult subjects with painful gallstone disease were randomized: 59 cases for LC and 41 cases for MC. Patients with gallstones shown on ultrasound with normal common bile duct and no history of icterus were included after an informed consent. Cases with acute cholecystitis and raised alkaline phosphatase were excluded. LC was performed using CO2 insufflation and a Storz 2D video camera. MC was done by transverse rectus cutting incision. Outcome was coded as success or failure. Success was defined as operation without injury to bile duct, viscera or vessels, minimal pain and discomfort at 4 weeks, no wound infection up to 4 weeks, and resumption of work within 2 weeks of operation. The total cost of each case included cost of investigations, cost of disposable articles for operation, cost of drugs, cost of hospital stay, and cost of operation including anesthesia. LC and MC were done with reusable instruments. A "societal viewpoint" has been taken in the cost calculations. RESULTS: There were 50/59 successful outcomes in LC and 15/40 outcomes in MC group. Total cost for LC was 386,769 rupees (Rs) and for MC was Rs 205,041. CE in LC was Rs 7,735 and in MC was Rs 13,669. Incremental CE ratio comparing LC with MC was 3,028.33. CONCLUSION: LC is a more cost-effective method for treatment of gallstone disease. PMID- 11758295 TI - A method for assessing the cost-effectiveness and the break-even point of clinical practice guidelines. AB - Assessing the costs and benefits of developing a clinical practice guideline is important because investments in guidelines compete with investments in other clinical programs. Despite the considerable number of guidelines in many industrialized countries, little is known about their costs and cost effectiveness. The authors have developed specific measures to determine the cost effectiveness of guidelines, using a German evidence-based guideline on obesity for the diagnosis and treatment of obese patients as a model. The measures are: the number of people needed to cure, the number of people needed to prevent from developing the disease in question, and the number of people to treat in order to break even. PMID- 11758296 TI - Economic analysis of treatment of functional dyspepsia. An assessment of the quality of published studies. AB - OBJECTIVES: The objective of this study was to assess the quality of economic analysis studies published in the medical and economical literature assessing the clinical management of functional dyspepsia. METHODS: Bibliographic search in the main biomedical databases, in articles from bibliographic references, health technology assessment reports, and in gray literature. A specific protocol with economic and clinical items was designed for the evaluation. RESULTS: Overall, 18 of 162 studies met the inclusion criteria for the assessment. The compared treatment options were very diverse. The main methodologic deficiencies were in perspective of analysis, inclusion of indirect costs, and sources of clinical information. CONCLUSIONS: Specific checklists with clinical and economical items may help to better assess the quality of economic analysis in the field of functional dyspepsia. The methodologic rigor in the application of economic analysis techniques, as well as the use of appropriate clinical outcome measures, is essential to guarantee the reproducibility of the studies. PMID- 11758297 TI - Quality assurance for screening mammography data collection systems in 22 countries. AB - OBJECTIVES: To document the mammography data that are gathered by the organized screening programs participating in the International Breast Cancer Screening Network (IBSN), the nature of their procedures for data quality assurance, and the measures used to assess program performance and impact. METHODS: A detailed questionnaire covering multiple aspects of quality assurance in screening mammography was mailed to IBSN representatives in 23 countries. RESULTS: Countries collect a wealth of screening mammography data, much of it computerized. Most countries have designated staff for data quality assurance. All provide staff training, and most have documentation requirements for data collection. Nearly all have one or more procedures to maintain data confidentiality. Countries are heterogeneous in collecting and assessing data to monitor screening program performance and impact. CONCLUSIONS: Demonstrating that population-based screening mammography reduces breast cancer mortality requires collection of high-quality data on key aspects of the multi-step screening process. Assuring the quality of data collection systems for screening mammography programs is an important and evolving area for IBSN countries. PMID- 11758298 TI - Panelists' views of 68 NIH consensus conference. AB - OBJECTIVES: To analyze the response patterns and trends of 68 surveys of successive NIH consensus panels' views on the NIH consensus process. METHODS: Each panel's responses were compared to an "average" panel's responses calculated by determining the mean response for each survey question across panels. RESULTS: The results show a stable pattern of panelists' generally positive views. However, several conferences were judged very positively and some very negatively compared to the norm. Most negatively viewed conferences occurred early in the consensus program's history. CONCLUSIONS: The disparate perceptions are discussed and interpreted as reflecting favorable panels' views of recent changes in the NIH Consensus Development Program. PMID- 11758299 TI - Assessment of new cardiovascular drugs. Relationships between considerations, professional characteristics, and prescribing. AB - OBJECTIVES: To study considerations used by professional and academic leaders to assess the position of new cardiovascular drugs in the therapeutic regimen in relationship to professional characteristics and the level of prescribing. METHODS: Interviews with 39 internists, cardiologists, general practitioners, and hospital pharmacists about considerations regarding the therapeutic position and prescribing of a new cardiovascular drug (losartan or atorvastatin) and professional characteristics. Considerations were classified according to Rogers' characteristics of an innovation, i.e., referring to the drug's relative advantage, compatibility, or complexity. Proportions of respondents mentioning advantageous, comparable, and/or disadvantageous characteristics were used to construct patterns to analyze an overall evaluation of the drugs in relation to professional characteristics and level of prescribing. RESULTS: The majority of considerations referred to the degree of relative advantage, but different subjects were emphasized for both drugs. Overall patterns of evaluation were generally intermediate and negative. The respondents' profession, mentioning commercial sources of information and self-qualification as a (moderately) early adopter of new drugs differentiated the overall evaluation of the drugs, in contrast to expertness and academic affiliation. The level of prescribing differentiated the overall evaluation only in the case of losartan. CONCLUSIONS: These professional and academic leaders critically evaluated the claims when assessing the position of the drugs in the therapeutic regimen but did not show consensus in their considerations. Accepted principles for prescribing were considered when assessing the therapeutic position of the drugs but resulted in varied tendencies for prescribing. PMID- 11758300 TI - Pharmacoeconomic component of a clinical trial conducted in Latin America. Conceptual and empirical considerations. AB - BACKGROUND: Although pharmacoeconomic studies constitute a valuable tool for better managing drug consumption, the conditions under which such studies would be performed in Latin American countries have not been explored. OBJECTIVES: The aim of this paper is to evaluate the potential advantages of and pitfalls in doing pharmacoeconomic research in Latin America and to propose avenues to facilitate the development of this field in the region. METHODS: The Canadian guidelines for the economic evaluation of pharmaceuticals served as a structured framework to assess, both prospectively and retrospectively, the conditions under which the pharmacoeconomic component of a clinical trial held in Mexico and Brazil would be and actually was conducted. RESULTS: The conditions under which pharmacoeconomic evaluations are conducted must be improved if studies are to contribute to the better management of scarce resources across the entire health care system. CONCLUSIONS: The creation of a public funding agency, the reappraisal of administrative data as a management tool in both the public and the private sectors, and the establishment of national guidelines should be considered within the framework of reforms aimed at allowing healthcare systems to meet their objectives of efficiency and equity. PMID- 11758301 TI - Private pharmacy practice and regulation. A randomized trial in Lao P.D.R. AB - OBJECTIVES: The objective of this study was to assess the effectiveness of government regulation of private pharmacy practice in a low-income country. METHODS: The intervention comprised inspections of the pharmacies, information, and distribution of documents to drug sellers and sanctions. It was implemented at two different intensity levels, active and regular intervention. The methods used to assess the effect of the interventions were interviews with the district drug inspectors, drug sellers and customers, inspection of drug purchases, and indicator surveys of pharmacies. Indicators for pharmacy-specific quality as well as for dispensing quality were developed. RESULTS: The main finding was one of strong overall improvements from initially low levels. The improvements were particularly marked by increases in the availability of essential materials for dispensing by 34% and in order in the pharmacy by 19%. Information given to customers increased from 35% to 51% and the mixing of different drugs in the same package went down from 17% to 9%. The pharmacies in the active intervention districts showed greater improvements for four of the six indicators, although statistically significant compared with the regular intervention districts only for the essential materials indicator. CONCLUSIONS: It was concluded that the regulatory activities have probably been an important factor behind the service quality improvements. It appeared feasible as well as effective to regulate private pharmacy practice in this particular low-income setting. PMID- 11758302 TI - Who uses self-care books, advice nurses, and computers for health information? AB - OBJECTIVES: While evaluating the effect of a community-wide informational intervention, this study explored access, health, and demographic factors related to the use of medical reference books, telephone advice nurses, and computers for health information. METHODS: A random sample of households in the intervention city (Boise, Idaho) and two control cities were surveyed about their use of health information in 1996. Shortly thereafter, the Healthwise Communities Project (HCP) distributed health information to all Boise residents. A follow-up survey was conducted in 1998. Overall, 5,909 surveys were completed for a 54% response rate. RESULTS: The HCP intervention was associated with statistically significant increases in the use of medical reference books and telephone advice nurses. The increased use of computers for health information was marginally significant. Few access, health, or demographic factors were consistently associated with using the different resources, except that people with depression used more of all three information resources, and income was not a significant predictor. CONCLUSION: Providing free health information led to an increase in use, but access, health, and demographic factors were also important determinants. In particular, poor health status and presence of a chronic illness were associated with health information use. These results suggest that healthy consumers are less interested in health information, and it may take other incentives to motivate them to learn about prevention and healthy behaviors. PMID- 11758303 TI - Methodologists and their methods. Do methodologists write up their conference presentations or is it just 15 minutes of fame? AB - OBJECTIVES: To assess the extent to which abstracts of methodological research, initially presented at meetings on systematic reviews, have gone on to be published as full articles. METHODS: Full publication was assessed in three ways: a search was carried out of The Cochrane Library; a search was conducted using MEDLINE; and a questionnaire was sent to the contact author of each abstract. RESULTS: Approximately half of the abstracts had not been, or were unlikely ever to be, published in full. CONCLUSIONS: The rate of full publication of abstracts related to the methodology of systematic reviews seems similar to that for randomized trials. PMID- 11758304 TI - A cost-minimization study of telemedicine. The case of telemonitored polysomnography to diagnose obstructive sleep apnea syndrome. AB - OBJECTIVES: In a context where sleep laboratories are overwhelmed by a growing demand to diagnose obstructive sleep apnea syndrome (OSAS), efficient substitutive solutions to in-laboratory polysomnography should be found. To compare the effectiveness and costs of home unattended polysomnography (Hpsg) and telemonitored polysomnography (TMpsg), a cost minimization study was performed. METHODS: In a crossover trial, 99 patients underwent on two consecutive nights TMpsg and Hpsg according to a randomized order. A legibility recording criterion was retained to measure effectiveness. A microcosting study of TMpsg and Hpsg was performed. The risks to adopt home strategy or telemonitored strategy, according to different scenario chosen to reach the diagnosis in case of failure of Hpsg or TMpsg, were analyzed. RESULTS: The recording was considered to be ineffective in 11.2% of TMpsg (95% CI, 4.9-17.4) and in 23.4% (95% CI, 19.12-27.68) of Hpsg. The effectiveness differential was 12.2% (95% CI, 1.8-22.6) (p = .02). Assuming that in case of failure PSGs would be re-realized in the same condition to reach the diagnosis, then TMpsg could be selected if Hc/TMc (cost of Hpsg/cost of TMpsg) > 0.97; Hpsg could be selected if Hc/TMc < 0.76. If 0.76 < or = Hc/TMc < or = 0.97, the choice of TMpsg would be ambiguous. TMc was estimated to be $244, while Hc was $153 (Hc/TMc = 0.63). CONCLUSION: Unless some specific geographical situations generate significant transport costs, the implementation of a strategy based on unattended polysomnography at home is cost-saving compared to a telemonitoring strategy. PMID- 11758305 TI - Assessment of the treatment costs of extracorporeal shock wave therapy versus surgical treatment for shoulder diseases. AB - OBJECTIVE: To determine the actual costs of extracorporeal shock wave therapy (ESWT) in patients with tendinitis of the supraspinatus muscle. METHODS: A comparison of the costs of surgical treatment versus the costs for ESWT was made. The total accrued costs were determined 12 weeks after intervention, using a sample group of 60 patients with calcifying or noncalcifying tendinitis of the supraspinatus muscle. RESULTS: The costs per case ranged from EUR 2,700 to EUR 4,300 per patient for ESWT and from EUR 13,400 to EUR 23,450 for surgical treatment, dependent on the method of calculation. Approximately 65% of the per patient cost is attributable to productivity losses in the workplace. CONCLUSIONS: In comparable short-term results, costs for operative treatment are 5-7 times higher than for ESWT. The greater trauma caused by an operative procedure leads to patients being off work for a longer period and thus a correspondingly higher social economic burden. PMID- 11758306 TI - Dynamic modeling in medical technology assessment. Fitting hearing aids in The Netherlands. AB - OBJECTIVES: The main objective of this article is to demonstrate the usefulness of dynamic modeling for an economic assessment of technology in health care. Specifically, this approach is applied to assess the impact of the use of hearing aids in Dutch health care. METHODS: The population is divided into different health classes between which, over time, transitions occur. Transition probabilities are derived from exogenous data. The transitions are associated with economic and societal costs and benefits. People who are satisfied with their hearing aids experience benefits. These benefits are expressed by quality adjusted life-years (QALYs). Costs are made during transitions (mainly the fitting of hearing aids). A cohort analysis is carried out, starting with people in a particular age group. The starting point is a fixed number of people within this age group, who are followed during their whole lifetime. RESULTS: Costs per QALY ratios are calculated for two health programs. The Fitting Hearing Aid Program describes the present situation in the Netherlands; the Post-purchase Counseling Hearing Aid Program is a hypothetical addition to the first program, where an intervention based on a Dutch study is undertaken to improve satisfaction with hearing aids. Future benefits and costs are discounted at a rate of 5%. CONCLUSIONS: The dynamic modeling approach provides a more realistic picture than a static approach. Particularly, the cost-effectiveness of the Fitting Hearing Aid Program is compared with the Post-purchase Counseling Hearing Aid Program. PMID- 11758307 TI - Cost consequences of sentinel lymph node biopsy in the treatment of breast cancer. A preliminary analysis. AB - OBJECTIVES: To assess whether sentinel lymph node biopsy (SLNB), an alternative to axillary lymph node dissection in treating female breast cancer, affords any cost savings. METHODS: We profile cumulative treatment costs of 811 breast cancer patients, 555 of whom received SLNB. Univariate and multivariate statistical tests are used to appraise whether these cost profiles differ between SLNB and other patients. RESULTS: The statistical results are mixed. However, none supports the conjecture that SLNB necessarily lowers the cost of treating the average breast patient. CONCLUSIONS: SLNB may be cost-effective, but longer term costs and outcomes must be estimated before firm conclusions can be reached. PMID- 11758308 TI - Report from the Swedish Council on Technology Assessment in Health Care (SBU). Chemotherapy for cancer. PMID- 11758309 TI - [Intraoperative photodynamic diagnosis of human glioma using ALA induced protoporphyrin IX]. PMID- 11758310 TI - [Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis]. AB - The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries. PMID- 11758311 TI - [A case of sinus pericranii manifesting as a parietal midline mass]. AB - A case of sinus pericranii was reported. A 5-year-old boy was admitted to our hospital, complaining of scalp mass located at the midparietal region. He was noticed to have had it since 3 years before. The mass decreased in size under mild compression, and during standing position, but increased in size due to lying down. Magnetic resonance imaging (MRI) demonstrated a mass with mixed signal intensity on the T1 weighted image and high signal intensity on the T2 weighted image. Gd-DTPA study showed irregular enhancement. Cerebral angiogram showed no communication between the mass and the superior sagittal sinus. Neither did direct injection of contrast medium into the mass revealed any communication. 3D-CT demonstrated three tiny bone defects beneath the mass. Open surgery revealed that the mass existed between the galea aponeurotica and the periosteum, which had a small communication with the emissary vein. Pathological examination showed a multiple lobular cyst with endothelial wall lining. This case report highlighted the fact that sinus pericranii with minimal communication with the dural sinus can be treated by removal of the mass and closure of the cranial bone abnormalities with bone wax without craniotomy. PMID- 11758312 TI - [Intracranial capillary hemangioma: a case report]. AB - Capillary hemangiomas are the most common tumor of the neck and head in children. Intracranial capillary hemangioma without generalized neuro-cutaneous hemangiomatosis is extremely rare, with only one report in the literature. We report a case of intracranial capillary hemangioma originating from the temporal base. An 8-year-old boy presented with a severe headache and nausea. A CT scan showed a low-density area in the left temporal lobe and an iso-density mass at the temporal base. This mass was enhanced by contrast medium. The mass lesion appeared as an iso-intensity area on T1-weighted MR images and as a high intensity area on T2-weighted MR images, and the mass was enhanced almost uniformly by gadoliniumdiethylene triaminepenta-acetic acid. Cerebral angiography showed abnormal staining fed by the anterior temporal artery. An operation was performed, and all of the tumor with the dura attached was removed. The histological diagnosis was capillary hemangioma. The tumor consisted of a proliferation of capillary vessels lined by a single layer of endothelial cells. In this paper, we review the clinical features, neuro-imaging findings and proposed etiology of capillary hemangioma. PMID- 11758313 TI - [Dissecting aneurysm of the posterior inferior cerebellar artery--studied by serial angiography]. AB - We report the case of a 34-year-old male with cerebellar hemorrhagic infarction caused by a dissecting aneurysm of the left posterior inferior cerebellar artery (PICA). The patient suffered from a headache and vomiting for two days and was transferred to our hospital with sudden deterioration of consciousness. On admission, he was semicomatose. A CT scan revealed hemorrhagic infarction in the left cerebellum and upward herniation. The emergency operation for posterior fossa decompression was performed. Postoperatively, his consciousness level improved promptly and he had no neurological deficits except for slight gait disturbance. The first vertebral angiography was performed on Day 27. It showed a sausage-like dissecting aneurysm of the left distal PICA. We planned conservative therapy with careful observation because of there being no indication for an operation. Serial angiography was performed and demonstrated the regression of the dissecting aneurysm on Day 258. Dissecting aneurysms of the distal PICA are rare and their natural history is not well understood. Conservative therapy for vertebrobasilar dissecting aneurysms has often been reported. We suggest that conservative therapy with serial angiography is the treatment of choice especially for ischemic-type dissecting aneurysms. We review 17 cases of dissecting aneurysm of the distal PICA in this study. PMID- 11758314 TI - [Multiple dural arteriovenous fistulas involving both the cavernous sinus and the posterior fossa: report of two cases and review of the literature]. AB - Multiple dural arteriovenous fistulas (DAVFs) are rare, accounting for 7% of all intracranial DAVFs. The authors describe two cases of multiple DAVFs involving both the cavernous sinus and the posterior fossa. The first patient was a 45-year old man who presented with visual disturbance, chemosis, exophthalmus, and tinnitus. Angiograms demonstrated DAVFs involving the right cavernous sinus and the ipsilateral sigmoid sinus. Soon after transarterial embolization via the right occipital artery, the patient's symptoms completely disappeared. Six months later, follow-up angiograms showed disappearance of the cavernous DAVF and a subtle opacification of the sigmoid sinus DAVF. The patient has been free from symptoms for four years. The second patient was a 75-year-old woman who presented with progressive tinnitus two years after stereotactic radiosurgery for right cavernous DAVF. Angiograms showed a new lesion in the contralateral transverse and sigmoid sinuses. Transvenous embolization (TVE) of the affected sinuses was successful and the patient's symptoms disappeared. The patient's course has been uneventful after treatment, and follow-up MR angiograms have not shown any recurrence of lesions. To our knowledge, 25 cases of multiple DAVFs have been reported in the literature, of which we reviewed 12 cases of multiple DAVFs affecting the cavernous sinus. The patients' ages ranged from 43 to 75 years with a mean of 57.4 and their distribution showed female predominance. Other DAVFs occurred mostly in the transverse and sigmoid sinuses. With the exception of our case (second patient), the posterior fossa lesions were located on the same side as the cavernous sinus DAVF. Multiple DAVFs were detected simultaneously in 5 of the 12 cases with the initial angiograms. In the other 7 cases, cavernous DAVFs had been treated, but were followed by posterior fossa lesions occurring after various intervals (4 months to 2.5 years). All the patients presented with ocular signs due to cavernous DAVFs. Based upon our review of the literature, we discuss here three possible hypotheses. The first possibility for formation of multiple DAVFs concerns their primary etiology, viz. that they develop after a huge sinus thrombosis involving several sinuses and its recanalization. A second possibility is the secondary formation of DAVFs. Preexisting cavernous sinus DAVFs induce sinus thrombosis and/or venous hypertension, which results in the formation of multiple lesions. A third possibility is that they are due to other factors, including increased angiogenic activity and some technical problems associated with TVE. Our review indicates that careful follow-up for several years should be made after treatment of cavernous DAVFs. PMID- 11758315 TI - [Multiple cerebral tuberculomas presenting with paradoxical expansion: a case report]. AB - A 24-year-old male presented with headache. He had been treated with antituberculous drugs for 19 months. MRI revealed 4 intracranial Gd-DTPA enhanced lesions surrounded by massive edema in the right frontal, both occipital and left basal ganglionic regions. Digital subtraction angiography showed no tumor stain. Two procedures for tumor resection were performed for the right frontal and left occipital regions, the latter of which definitively diagnosed by the polymerase chain reaction method. The tumors were well demarcated, showed a rough surface, and were elastically hard. The two residual lesions responded differently to chemotherapy. The lesion in the right occipital region decreased in size, while the other in the left basal ganglionic region continued to grow gradually 26 months after the antituberculous chemotherapy was started. According to previous reports, treatment should be continued for as long as 12-30 months in cases showing paradoxical expansion. In this case, the left basal ganglionic lesion began to decrease in size after 28 months of administration of anti-tuberculous drugs. We report successful treatment of a case of multiple tuberculomas presenting with paradoxical expansion managed by a combination of surgery and continuous chemotherapy. PMID- 11758316 TI - [Angioplasty with stenting for intracranial vertebral and basilar artery stenosis: three technical case reports and literature review]. AB - Patients with intracranial vertebral artery (VA) or basilar artery (BA) stenosis have been mainly treated with medication. However, it has been reported that about 10% of patients experience restroke in the VBA territory, with a high rate of morbidity and mortality. Percutaneous transluminal angioplasty (PTA) is regarded as one of the treatments although it carries the risk of restenosis, recoil or dissection. Stent placement is, therefore, considered to be a further option for the treatment of intracranial artery stenosis since it can prevent the restenosis. We report three medical refractory cases of intracranial VA (2 cases) or BA stenosis (1 case) treated with stenting, none of which had complications and their symptoms disappeared or diminished. Angioplasty with the use of a stent device is regarded as a useful treatment for intracranial artery stenosis, but its risk and long-term result need to be investigated further. PMID- 11758317 TI - [Dissecting aneurysm of the anterior cerebral artery with persistent pearl & string sign on cerebral angiograms over a period of eight years]. AB - We present a rare case of a dissecting aneurysm of the left anterior cerebral artery (ACA) with persistent pearl & string sign on cerebral angiograms over a period of 8 years. A 43-year-old woman with disturbance of consciousness and right sided hemiparesis was conservatively treated. Computed tomographic (CT) scan revealed a low-density area in the left frontal lobe. Initial angiography, which was performed at 6 months after the onset, showed a pearl & string sign at the A2 portion of the left ACA. After 8 years, repeat angiography again showed persistent pearl & string sign at the same portion of the left ACA. We discussed the changes in findings usually obtained in cerebral angiography concerning dissecting aneurysms in ACA. PMID- 11758318 TI - [Penetrating head injury caused by an icepick]. AB - The patient was a 39-year-old man, with a three year history of schizophrenia, who attempted suicide by piercing his head with an icepick. Spinal cord injuries and shock caused by falling from the fifth floor of the building following this penetrating injury were also noted on admission. The CT scan revealed that the icepick had deeply penetrated the posterior fossa from the forehead. No new neurological deficits or cerebrospinal fluid leakage appeared after admission. The icepick was removed completely without difficulty. In penetrating head injuries, early assessment with cerebral angiography to determine the extent of vascular injury is useful for deciding if surgery should be performed. PMID- 11758319 TI - [Clinical trial of bradykinin-enhancing chemotherapy for a recurrent malignant glioma: a case report]. AB - Patients with malignant glioma undergo a combined treatment with surgical resection, radiotherapy, and chemotherapy. Although those treatments usually show some restraining effects on the tumor, a relapse occurs in most of the patients within a few years. We have investigated the feasibility and safety of intra arterial chemotherapy for malignant brain tumors by enhancing vascular permeability using intra-arterial bradykinin infusion. In 2001, The Committee of Ethics in Kyushu University approved our clinical trial of the bradykinin enhancing chemotherapy for recurrent malignant gliomas. We here report the first case of our clinical trial. A 31-year-old man, who had undergone surgical resection followed by chemotherapy and irradiation for malignant progression of the left frontal astrocytoma over a period of 2 years, had a relapse of the tumor in the bilateral frontal lobes. After obtaining informed consent, bradykinin and carboplatin were infused through a microcatheter at the left A1 portion under general anesthesia. By dose escalation of bradykinin, the enhanced lesion in the bilateral frontal lobes diminished on magnetic resonance imaging after 3 trials with 3-week intervals, regardless of new lesions outside of the treated area. No neurological or physiological complication including myelosuppression was noted. Bradykinin-enhancing chemotherapy appeared to be effective and safe for malignant glioma. Because it was able to increase drug delivery to the tumor, it was possible to reduce the size of the dose of chemotherapeutic agent, which resulted in minimum complication. PMID- 11758320 TI - [Change of cross-sectional area of the right internal jugular vein: effect of Trendelenburg position and valsalva maneuver]. AB - To compare the effect of Valsalva maneuver and 10 degrees Trendelenburg position on the right internal jugular vein (RIJV), we measured RIJV cross-sectional area using ultrasound imaging during these procedures. The study group consisted of 13 normal healthy volunteers (6 males, 7 females, aged 25-47) with no history of neck surgery or right internal jugular vein (RIJV) puncture. All ultrasound images were obtained at the level of the cricoid cartilage. The subjects were positioned supine, and the measurements were taken with the subjects supine, under Valsalva maneuver, and under 10 degrees Trendelenburg tilt position. The cross-sectional areas of the RIJV during Valsalva maneuver and 10 degrees Trendelenburg position compared to those with supine position were 314 +/- 162%, and 192 +/- 96%, respectively. We conclude that both procedures increase cross sectional area of IRJV significantly and in this respect Valsalva maneuver is more effective than Trendelenburg position. PMID- 11758321 TI - [Evaluation of peripheral facial nerve palsy with R 2 wave latency in blink reflex]. AB - Electrically elicited blink reflexes were investigated in 60 patients with peripheral facial nerve palsy. The purpose of this study was to evaluate the utility of analysis of R 2 wave in blink reflex as a prognostic indicator for the patients with facial palsy. The patients treated by stellate ganglion block were classified into three groups: Group I scored more than 90 points (full score is 100 points) within 2 weeks, Group II scored more than 90 points over 2 weeks, and Group III scored less than 90 points. The examinations were performed at the first visit, and 2, 4, 6 weeks after the onset of facial palsy. Latencies of ipsilateral and contralateral R 2 wave were measured by electrical stimulation on both side. There were significant differences of R 2 latency between ipsilateral and contralateral side in each of the three groups at the first visit. In Group II, contralateral R 2 latency obtained by stimulation of the paralytic side was prolonged significantly. In Group III, the ipsilateral R 2 wave was not observed. The results of this study indicate that measurement of the R 2 latency of blink reflex is useful in judging the severity of the peripheral facial nerve palsy. The R 2 latencies obtained by stimulation of ipsilateral and contralateral side should be used as one of the parameters for evaluation of the prognosis of patients with peripheral facial nerve palsy. PMID- 11758322 TI - [Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection]. AB - To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P < 0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P < 0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain. PMID- 11758323 TI - [Evaluation of postoperative pain relief by infiltration of bupivacaine or epidural block after laparoscopic cholecystectomy]. AB - We compared the analgesic effect of bupivacaine infiltration into surgical wounds with that of epidural block after laparoscopic cholecystectomy (LC). Forty-five patients (ASA physical status I-II) for LC were randomized into three groups (n = 15 in each group). Patients received only general anesthesia (Group C), received infiltration of 0.5% bupivacaine into the surgical wound before surgery combined with general anesthesia (Group L), or received epidural anesthesia combined with general anesthesia (Group E). Postoperative pain was assessed using visual analogue scale (scale: 0-10) at 1, 2, 6 and 12 hours after the operation, the need for additional supplemental analgesics, and the cost of anesthesia. Visual analogue scale in Group C at 1, 2, or 6 hours was significantly greater than that of Group L and E. The number of patients who needed supplemental analgesics was 9 in Group C, 5 in Group L, and 2 in Group E. The cost of pharmaceutical and anesthetic practice of Group E was more expensive than Group L and C. In conclusion, infiltration of bupivacaine combined with general anesthesia is an effective and economical method of postoperative pain relief. PMID- 11758324 TI - [The effect of obesity on spinal anesthesia for cesarean section]. AB - To evaluate the effect of obesity on spinal anesthesia for cesarean section, we retrospectively studied 90 parturients who had undergone cesarean section, dividing the patients into 2 groups: obesity group (body mass index > 30, n = 41); control group (body mass index < 30, n = 49). Total surgical time and anesthetic time were longer in the obesity group than in the control group. The amount of ephedrine administered was also greater in the obesity group than in the control group. However, there were no significant differences in time for spinal tap and the incidence of hypotension between the two groups. Spinal anesthesia for cesarean section in obese patients may be an acceptable method. PMID- 11758325 TI - [Anesthetic management using propofol and fentanyl for transrectal ultrasound guided prostatic biopsy]. AB - We prospectively evaluated the efficiency of the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy. In the anesthetic management for the transrectal, ultrasound-guided, prostatic biopsy, it is required to obtain enough muscle relaxation of the anal sphincter for placing the transrectal ultrasound probe and to secure immobilization of the patient during the prostatic biopsy. Eight patients undergoing the transrectal, ultrasound-guided, prostatic biopsy participated in this study. Without premedication, anesthesia was induced using fentanyl (100 micrograms) and target controlled infusion of propofol with an estimated blood concentration of 3 micrograms.ml-1. We obtained both sufficient muscle relaxation of the anal sphincter and complete immobilization of the patient during the prostatic biopsy in all patients. Moreover, this anesthetic management assured short awakening time from anesthesia and low incidence of adverse effects. From these results, we conclude that the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy is efficient and practical. PMID- 11758326 TI - [The effect of lidocaine on the bispectral index during anesthesia induction with propofol]. AB - We investigated the effect of premixing lidocaine with propofol on a bispectral index (BIS) during propofol infusion. We studied 40 adult patients given mixture of 1% propofol 20 ml with 2 ml of normal saline (control group) or 2% lidocaine (lidocaine group) infused at 2 ml.kg-1.hr-1 for 10 minutes. Heart rate, mean arterial pressure, and BIS were measured every minute. The addition of lidocaine to propofol reduced the incidence of injection pain from 85% to 10% but did not change the induction time. Propofol significantly decreased mean arterial pressure and BIS but there was no difference between the groups. In conclusion, premixing lidocaine with propofol reduces injection pain without affecting the hypnotic effect. PMID- 11758327 TI - [Propofol anesthesia combined with thoracic epidural anesthesia for thymectomy for myasthenia gravis--a report of eleven cases]. AB - We report 11 cases of thymectomy for myasthenia gravis using propofol and thoracic epidural anesthesia. Considering the influence of nitrous oxide to environment and muscular relaxation of volatile anesthetics, we selected this anesthetic method. By proper sedation with propofol and sufficient analgesia with epidural anesthesia, the hemodynamics during operation was stable and the emergence was rapid. The patients were extubated early after operation except in one case in which oxygenation was not good because of sputum. We conclude that our anesthetic method is useful. Moreover, we applied Fuchu hospital scoring system for prediction of the need of postoperative mechanical ventilation in patients with myasthenia gravis to the present 11 cases. These predictions corresponded well with the results. Therefore Fuchu hospital scoring system is useful for managing these patients by our anesthetic method. PMID- 11758328 TI - [Perioperative management of a patient with systemic lupus erythematosus, myasthenia gravis, and pemphigus foliaceous]. AB - A 38-year-old female with systemic lupus erythematosus (SLE), myasthenia gravis (MG), and pemphigus foliaceous (PF) was scheduled to undergo total hysterectomy and lymphadenectomy. Preanesthetic examination revealed anemia, a prolonged activated partial thromboplastin time, and a reduced percent vital capacity. Antiphospholipid antibody was not positive. After treating the bullous lesions of PF and the muscle weakness due to MG (noted on admission for surgery) with oral prednisolone, the patient was scheduled for surgery. To avoid the use of a muscle relaxant and the potential complications of the airway manipulation involved in using a laryngeal mask or endotracheal tube, since the patient had MG and PF, a regional anesthetic technique was selected. This involved continuous epidural anesthesia, achieved using 1% or 2% mepivacaine, with sedation by a combination of propofol infusion (3 mg.kg-1.hr-1) and nitrous oxide (60% in oxygen). The patient breathed spontaneously under the mask throughout the 3.5-hr operation. The intraoperative surgical and anesthetic course was uneventful. After a benign postoperative course, the patient was discharged on the 16th postoperative day. PMID- 11758329 TI - [Propofol-fentanyl anesthesia for a 13-year-old patient with Beckwith-Wiedemann syndrome]. AB - We report anesthetic management of a 13-year-old boy with Beckwith-Wiedemann syndrome for urethral fistulectomy using propofol-fentanyl anesthesia. The syndrome has three major symptoms; exomphalos, macroglossia and gigantism. Other complications including neonatal hypoglycemia, visceromegaly, metabolic disorders, malignant tumors, and cardiovascular abnormalities may also be seen. This patient was complicated with gigantism, exomphalos, hypospadias, cryptorchidism, hepatoblastoma, accessory mammae, and left axis deviation with left anterior fascicular block. A comprehensive preoperative examination should include assessment of the airway, cardiovascular conditions, endocrine status, blood glucose, and electrolytes. In this patient, airway management was easy by laryngeal mask airway and the anesthetic course was uneventful. PMID- 11758330 TI - [Anesthetic management of a patient with Cockayne's syndrome]. AB - Cockayne's syndrome is a disease of childhood characterized by mental retardation and premature aging. An 11-year-old girl with Cockayne's syndrome underwent general anesthesia for acute appendicitis. Although we had expected the difficulty of intubation because of her small jaw with limited movement, we could visualize her vocal cord, and intubate easily. High peak airway pressure was needed to ventilate her lung after intubation suggesting decreased lung compliance for this syndrome. We have to consider anesthetic problems resulting not only from pediatric but also from geriatric anesthesia for the management of this syndrome. PMID- 11758331 TI - [A case of atropine-resistant bradycardia in a patient on long-term lithium medication]. AB - A 44-year-old woman was scheduled for laparoscopic cholecystectomy and partial thyroidectomy. She had received lithium, 400-1200 mg daily, and other antidepressants for 10 years for her depressive disorder. Preoperative examination revealed a swelling of the right thyroid associated with hypothyroidism. Her heart rate was in the range of 45-70 min-1 preoperatively. After induction of anesthesia with propofol 50 mg, and fentanyl 100 micrograms, heart rate decreased to 36 min-1 and remained low after tracheal intubation. Atropine sulfate 1.1 mg in divided doses, and ephedrine 4 mg i.v. did not change the heart rate. However, a bolus of isoproterenol 0.02 mg i.v. increased the heart rate to 95 min-1. We suspect that atropine-resistant bradycardia was due to sinus node dysfunction produced by interaction of chronic lithium treatment, fentanyl and propofol. Therefore, an intractable sinus node dysfunction may occur in a patient in whom lithium is given chronically, particularly in whom hypothyroidism is associated. In such a patient, a beta-adrenergic stimulant may be effective in treating bradycardia. PMID- 11758332 TI - [Two pediatric cases of malignant hyperthermia caused by sevoflurane]. AB - We experienced two cases of malignant hyperthermia (MH) triggered by sevoflurane. Case 1 was a six-year-old girl, 15.8 kg, undergoing strabismus repair. She had flat back, elevated diaphragm and high arched palate. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Her trachea was intubated without the use of muscle relaxant. Thirty minutes after the induction of anesthesia, ETco2 was over 60 mmHg despite hyperventilation. Muscle rigidity of legs and the rise in temperature were noted. MH was diagnosed and dantrolene i.v. was administered. Her maximum esophageal temperature was 40.2 degrees C. ETco2 and temperature returned to baseline values after dantrolene administration. Creatine phosphokinase (CK) level was 252 U.l-1 preoperatively, and 1690 U.l-1 next day. Case 2 was a year-and-9-month-old boy undergoing accessory ear resection. Anesthesia was induced with sevoflurane and nitrous oxide in oxygen. His trachea was intubated with an aid of vecuronium. Forty minutes after administration of sevoflurane his temperature rose to 38.6 degrees C with heart rate 191 bpm and Spo2 93%, and muscle rigidity of legs. MH was diagnosed and dantrolene was administered. His highest temperature was 39.3 degrees C and was reduced promptly after dantrolene. Postoperatively he was noted to have downslanting palpebral fissures, micrognathia, low set ears, and a single crease of the fifth finger and diagnosed as King syndrome which is reported to have association with MH. Both patients had no history of anesthesia nor abnormal family history. Both of them were rescued with dantrolene and recovered without sequelae. PMID- 11758333 TI - [Severe laryngeal edema after tracheal extubation--report of a case]. AB - An 80-year old female underwent subtotal esophagectomy with neck lymphnode dissection for esophageal cancer. The tracheal intubation was done repeatedly. Anesthesia was maintained with O2-N2O-isoflurane. No complications were observed during the operation. About thirty minutes after tracheal extubation, she developed airway obstruction with tracheal tug and stridor. Severe laryngeal edema was found by bronchofiberscopy. Percutaneous minitracheostomy was performed under ventilation support by laryngeal mask airway. Seven days later, bronchoscopy examination revealed that the laryngeal edema had disappeared. It should be kept in mind that severe laryngeal edema could develop immediately after extubation. PMID- 11758334 TI - [Endotracheal intubation with a lighted stylet in a patient with difficult airway from the first and second brancheal arch syndrome]. AB - A 28 year-old-woman with the first and second brancheal arch syndrome was scheduled for the lift of the inferior part of the right ear. Difficult intubation was expected because of the mandibular hypoplasia. We chose a lightwand stylet for tracheal intubation. Anesthesia was induced with sevoflurane slowly increased to 5% in nitrous oxide 3 l.min-1 with oxygen 3 l.min-1. A spiral tube with 6.5 mm inner diameter (Safety-Flex, Mallinckrodt Medical, Ireland) was attached to the lightwand stylet (Surch-Light, Aaron, U.S.A.) and shaped to fit to pharyngo-laryngeal curve. Under spontaneous breathing, the tube was successfully inserted without laryngoscopy. No traumatic events occurred. Usually fiberoptic laryngoscopy requires more skill, more expensive equipment, and more time to prepare than the lightwand stylet technique. Moreover profuse secretions or blood in the oropharynx sometimes inhibit clear vision by fiberoptic laryngoscopy. The lightwand stylet is simple and inexpensive and it is useful for tracheal intubation in patients with difficult airway from the first and second brancheal arch syndrome. PMID- 11758335 TI - [A case of amphetamine-induced down-regulation of beta-adrenoceptor]. AB - A 29-year-old man with severe pyloric stenosis confessed that he had been a chronic amphetamine abuser just after awakening from anesthesia for partial gastrectomy. Anesthesia was maintained with thoracic epidural bupivacaine combined with continuous i.v. infusion of propofol. Decreased arterial blood pressure was observed 10 min after starting epidural anesthesia, and remained stable at 80-90 mmHg of systolic blood pressure in spite of massive fluid resuscitation in addition to repeated i.v. administration of ephedrine/methoxamine and continuous i.v. infusion of dopamine at a rate of 8 micrograms.kg-1.min-1. Finally, arterial blood pressure rose gradually after i.v. administration of methylpredonisolone 500 mg. We speculate that the down regulation of beta-adrenoceptor induced by the sympathomimetic action of amphetamine, might be a major cause of refractory hypotension. PMID- 11758336 TI - [Anesthetic management of a patient with von Recklinghausen disease complicated with spinal tumor and severe spinal deformity]. AB - We had three occasions of giving anesthesia to a patient with von Recklinghausen disease complicated with spinal tumor and spinal deformity. A 49-year-old male patient who had suffered from von Recklinghausen disease since 35 years of age developed slight low respiratory function due to neurofibroma in the spinal canal and the paravertebral lesion and severe kyphoscoliosis in the lumbar spine which were checked by lumbar X-ray, abdominal ultrasonography and computed tomography during the preoperative period. Transurethral biopsy of the bladder tumor, internal urethrotomy for the urethral stricture and vesical lithotripsy for the bladder stone were performed under general anesthesia. Elevated position of his head and lower extremities and slight right lateral decubitus position were employed during anesthetic induction and semi-Trendelenburg's position during anesthetic maintenance. Convalescence after each operation was uneventful. He was comfortable and had a safe perioperative course. He showed no unward change in neurological symptoms during the post-operative period. This case suggests that we must take the complication such as spinal tumor and spinal deformity into consideration for anesthetic management of patients with von Recklinghausen disease and select the appropriate anesthetic method and patient's position. PMID- 11758337 TI - [Swelling of the tongue after intraoperative monitoring by transesophageal echocardiography]. AB - Tongue swelling after surgery is a rare but potentially lethal postoperative complication. This is a case report of a 62-yr-old patient who developed tongue swelling after intraoperative monitoring by transesophageal echocardiography. The patient underwent replacement of the descending aorta with an interposition graft under cardiopulmonary bypass. A transesophageal echocardiography (TEE) probe was inserted after the induction of general anesthesia. Surgery and anesthesia were uneventful. After the surgical procedure, the TEE probe was removed. At that time, marked swelling of the tongue was noted. However, there was no diffuse edema in the neck, face, supraglottic structures or the larynx. The tongue swelling was thought to have been caused by local mechanical compression of the tongue with the TEE probe. The tongue returned to normal size the next day. Care should be taken to prevent the occurrence of this complication during and after TEE examination under general anesthesia. PMID- 11758338 TI - [A case of long-term respiratory management following resection of a huge facial hemangioma]. AB - A 49 year-old-woman was scheduled for resection of a huge hemangioma of the face and neck region. After the resection, severe edema developed on the tongue, larynx, and pharynx even leaving no space between the tracheal tube and these tissues. Prolonged respiratory management with endotracheal tube intubation was needed to maintain the upper airway for more than three weeks. Tracheostomy was performed 27 days after the operation. Two weeks later, the edema of the upper airway subsided. Thereafter her clinical course was uneventful, and she was discharged 22 days after the tracheostomy. Resection of a huge facial and neck hemangioma should be carefully managed as it can be followed by unexpected severe postoperative upper airway edema leading to suffocation. PMID- 11758339 TI - [Epiduroscopy in patients with chronic low back pain without remarkable findings on magnetic resonance imaging]. AB - Two patients with chronic low back pain and sciatica failed to respond to conservative treatments. In these patients, magnetic resonance imaging (MRI) showed no remarkable findings corresponding to their symptoms. We treated these patients using epiduroscopy. Epiduroscopic visualization of the spinal canal permits efficient adhesiolysis and irrigation. One patient got better after two epiduroscopic procedures, and the other did not. Epiduroscopy may be an effective, minimally invasive treatment as well as examination for patients with chronic low back pain without remarkable findings on MRI. PMID- 11758340 TI - [Annual study of perioperative mortality and morbidity for the year of 1999 in Japan: the outlines--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety]. AB - Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994 1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events. PMID- 11758341 TI - [Problems in the ophthalmic examination of post-LASIK eyes]. PMID- 11758342 TI - [Studies on kinetic viscoelasticity of slow muscle fibers--2. Dynamic stiffness changes studied by quick release method and frequency response method]. AB - PURPOSE: To evaluate the mechanical properties of slow fibers and fast fibers which make up the extraocular muscles in rabbits. SUBJECTS AND METHOD: I studied the contractile properties and viscoelastic properties of the superior rectus muscle(SR) and the retractor bulbi muscle (RB) of rabbits using the quick release method and the frequency response method. RESULTS: In the quick release method, isometric tension transients were slower in the SR than in the RB. In the frequency response method, the muscle length is perturbed sinusoidally to measure kinetic viscoelasticity. In resting muscle, dynamic stiffness was not changed with increasing frequency. In contracted muscle, dynamic stiffness was increased with increasing frequency, and the rate of increase was greater in the SR than in the RB. CONCLUSION: It was concluded that the viscoelasticity of the activated cross bridge is greater in slow fibers than in fast fibers. PMID- 11758343 TI - [Safety studies on collagen viscoelastic substance as an auxiliary agent in anterior segment surgery--assays of anti-collagen antibodies in blood and residual concentration of collagen in the anterior chamber of rabbits]. AB - PURPOSE: Alkali-soluble collagen solution was assessed as a possible viscoelastic substance in anterior segment surgery, in terms of its safe applicability by assaying antigenicity, disappearance rate of collagen from the anterior chamber, and histopathological effect on the corneal tissue. METHODS: The aqueous humor of rabbits was replaced with collagen solution three times. Then, follow-up clinical examinations with hand-slitlamp-microscopy, tonometry, pachymetry, and specular microscopy as well as ophthalmic histopathological examination were performed. Remaining collagen concentration in the aqueous humor at 1, 3, 5, 8, 24 and 72 hours after injection was determined to evaluate the disappearance rate of collagen from the aqueous humor with time. In vivo effects of chemical modification of collagen and buffer concentration on the corneal tissue were further studied by using transmission electron microscope (TEM) to find an optimum condition for collagen application. RESULTS: Neither anti-collagen antibody formation, nor inflammatory responses in the anterior segment and systemic symptoms were observed even after 3 injections of collagen solution, except for 1 case which showed corneal opacity. As much as 97.4% of the collagen injected into the anterior chamber disappeared from the eyeball. On the basis of TEM findings, succinylated collagen in diluted phosphate buffer seems to be superior to alkali soluble collagen in terms of corneal tissue protection. CONCLUSION: Collagen specifically prepared for this study showed no antigenecity and disappeared promptly from the anterior chamber. The optimal form of collagen in terms of corneal protection was discussed. PMID- 11758344 TI - [Epidemiologic study of diabetic retinopathy in nine hospitals in the Aomori area]. AB - PURPOSE: To examine the prevalence of diabetic retinopathy and the relationship between diabetic retinopathy and systemic risk factors. METHODS: A cross sectional study of diabetic retinopathy was conducted on 1,826 eyes of 913 randomly selected patients with type 2 diabetes in 9 central hospitals in Aomori Prefecture and the surrounding district. Retinopathy levels and maculopathy were assessed by binocular funduscopy, fundus photography and, if necessary, by fluorescein angiography. Multiple logistic regression analysis was performed to determine independent effects of systemic risk factors on diabetic retinopathy. RESULTS: The prevalence of background retinopathy was 31%, of preproliferative retinopathy 5%, and of proliferative retinopathy 5% in all patients. However, in 3 hospitals in which the patients were routinely examined by fluorescein angiography, background retinopathy was found to be present in 60%, preproliferative retinopathy in 5%, and prolifertive retinopathy in 7%. Maculopathy was found in 8% of diabetic patients and the prevalence was 11% in the eyes with background retinopathy, 40% with preproliferative retinopathy, and 50% with proliferative retinopathy. Multiple logistic regression analysis showed that retinopathy was significantly associated with duration of diabetes, methods of diabetic control, hypertension, nephropathy, and neuropathy. CONCLUSION: The detection rate of background diabetic retinopathy by fluorescein angiography was twice as sensitive as that by binocular funduscopy and fundus photography. The prevalence of maculopathy increases with the progression of retinopathy. Several systemic risk factors have significant association with diabetic retinopathy and maculopathy. PMID- 11758345 TI - [Supraciliochoroidal fluid at an early stage after trabeculectomy]. AB - PURPOSE: To examine the supraciliochoroidal fluid(SCF) by ultrasound biomicroscopy(UBM) at an early stage after trabeculectomy. SUBJECTS AND METHODS: Fifteen eyes without post-operative complications were examined by UBM before the operation and less than 2 weeks after trabeculectomy with mitomycin C. RESULTS: SCF was detected postoperatively in 6 eyes. One eye had choroidal detachment under indirect-ophthalmoscope and 5 eyes(33%) had SCF without choroidal detachment. The SCF in 4 eyes disappeared within 4 weeks after trabeculectomy. The intraocular pressure was 6.4 +/- 3.4 mmHg(mean +/- standard deviation) when SCF was detected and it rose to 13.2 +/- 7.2 mmHg when SCF disappeared. The intraocular pressure was 11.4 +/- 4.0 mmHg in the eyes without SCF, which was significantly higher than in the eyes with SCF. CONCLUSION: At an early stage after trabeculectomy, SCF was detected by UBM in some cases without ophthalmoscopic choroidal detachment. Compared with the reported frequency of SCF after 3 or 6 months, our study revealed that SCF was present more frequently at an early stage after trabeculectomy. Our results may indicate that the presence of SCF is related to early low intraocular pressure and that disappearance of SCF induces the elevation of intraocular pressure. PMID- 11758346 TI - [Underestimation of intraocular pressure after laser in situ keratomileusis]. AB - PURPOSE: We reviewed 115 eyes of 65 patients regarding the intraocular pressure(IOP) following laser in situ keratomileusis(LASIK). PATIENTS AND METHODS: The ages averaged 31.2 +/- 10.5(mean +/- standard deviation) years. The preoperative spherical equivalent averaged -6.85 +/- 2.54 (mean +/- standard deviation) D. A noncontact pneumatic tonometer and Goldmann applanation tonometer were used in measuring the IOP. RESULTS: The IOP difference before and after surgery was statistically significant(Mann-Whitney U test). The IOP was significantly corrected with the corrected diopter value, corneal thickness, and corneal curvature(Spearman coefficient by rank). CONCLUSION: The findings show that postoperative IOP may be underestimated due to decreased corneal thickness and curvature. Due attention has to be paid to this feature in evaluating IOP after LASIK. PMID- 11758347 TI - [Correlation between blue chromatic macular sensitivity and optic disc change in early glaucoma patients]. AB - PURPOSE: To investigate the relationship between morphological changes of the optic nerve head (ONH) and macular sensitivity(MS) determined with blue-on yellow(B on Y) and white on white (W on W) perimetry in normal subjects and patients with glaucoma. METHODS: One randomly chosen eye was evaluated in each of 28 normal subjects, 23 patients with ocular hypertension(OH), and 23 patients with early primary open-angle glaucoma(POAG). Mean values for MS by B on Y and W on W perimetry were obtained with the macular program using a modified Humphrey Field Analyzer(HFA). The Heidelberg Retina Tomograph(HRT) with software version 2.01 was used to evaluate the topographic parameters of temporal sector in ONH. RESULTS: There was no significant difference in temporal topographic parameters of ONH among the three clinical groups. Mean values for MS of B on Y and W on W perimetry in early POAG were significantly lower than in normal subjects and OH. Mean values for MS of W on W perimetry showed no significant correlation with ONH parameters of the temporal sector. In early POAG, mean values for MS of B on Y perimetry significantly correlated with cup area, cup/disc area ratio, cup volume, and rim volume in the temporal sector of ONH. CONCLUSION: The measurement of mean MS of B on Y might be able to detect the glaucomatous optic nerve damage due to increased intraocular pressure prior to the morphological changes of ONH in early stages of glaucoma. PMID- 11758348 TI - [Examination of eye position after strabismus surgery in Kawasaki Medical School Hospital]. AB - PURPOSE: To examine the factors which affect changes in the position of the eyes following the strabismus surgery. METHODS: The postoperative position of 240 eyes with concomitant strabismus was examined. The factors which seemed to have an effect on the position of the eyes were enumerated, and a logistic regression analysis of the results was done. RESULTS: In comparison with esotropia, in exotropia the eyes showed a tendency to return gradually to a normal position. There was no remarkable improvement in stereoscopic vision following strabismus surgery. Based on the standards of the Japanese Association of Strabismus and Amblyopia [the cure standard for strabismus], the results of strabismus surgery were as follows: Grade 1(cosmetically satisfactory) was mainly observed for esotropia, and Grade 3(good) for exotropia. The factors which had a significant effect on the postoperative position of the eyes were as follows: esotropia amblyopia, muscle movement, and operative methods; exotropia: retinal correspondence, operative methods, and the necessity of inferior oblique muscle surgery. CONCLUSIONS: There was little correction of the position of the eyes. In individual cases, the factors which affect position of eyes were examined, and it was considered necessary to increase the amount of correction. Age is a factor which has an effect, but the effect on esotropia and exotropia is small. PMID- 11758349 TI - [Visual outcome of macular hole surgery with internal limiting membrane peeling]. AB - PURPOSE: To evaluate the efficacy of the internal limiting membrane(ILM) peeling on macular hole surgery. METHODS: A series of 102 patients(105 eyes) who underwent primary macular hole surgery between October 1994 and April 1999 was used for this retrospective study. The mean age was 65.6 +/- 7.1 years (mean +/- standard deviation). Of the study eyes, 34 eyes(32%) had a Stage II hole, 49 eyes(47%) had a Stage III hole, and 22 eyes(21%) had a Stage IV hole based on the Gass classification. Here we compared the surgical and visual outcome of the ILM peeling-treated group(treated group: 51 eyes) with those of ILM peeling-untreated group(untreated group: 54 eyes). RESULTS: The hole closure rate after initial surgery was 98.0% in the treated group and 90.7% in the untreated group, and mean postoperative visual acuity, excluding cases where the hole was not closed by initial surgery, was 0.44 and 0.47, respectively. Visual improvement of 2 or more lines on Snellen chart was achieved in 84.3% and 57.4%(p < 0.01), and that of 4 or more lines in 54.9% and 25.9% (p < 0.01), respectively. Of the eyes with Stage II and III holes, visual outcome of the treated group was significantly better than that of the untreated group(p = 0.034, p = 0.037). In Stage IV, the initial closure rate of the treated group was significantly better than that of the untreated group(p = 0.02), but the visual outcome was not significantly different. CONCLUSION: Vitreous surgery combined with ILM peeling for the management of idiopathic macular hole is effective not only on hole closure but also on visual recovery. PMID- 11758350 TI - [Clinical evaluation of renal angiomyolipoma]. AB - Between April 1980 and December 1999, 23 kidneys in 20 patients were diagnosed as having renal angiomyolipoma at our institution. The patients were 6 males and 14 females aged 24 to 79 years, with a mean age of 55.4 years. Two patients had associated tuberous sclerosis and 3 had bilateral disease. Of all patients the main clinical symptoms were pain (45%) and palpable mass (40%); 5 patients (25%) had asymptomatic lesions. The size of the tumor ranged from 1.3 to 24 cm (mean 7.7 cm). Treatment consisted of nephrectomy in 9 patients, partial nephrectomy in 6 and selective embolization in one. Pre-operative diagnosis was renal cell carcinoma in 5 of the 9 patients who underwent nephrectomy. Six patients with 7 diseased kidneys were followed radiologically. One patient underwent percutaneous biopsy to confirm the diagnosis. We suggest that nephron-sparing surgery for patients with renal angiomyolipoma should be the first step if tumor size is 4 cm < or = or increasing rapidly. Selective embolization is also a useful method. However, we need long-term follow-up to evaluate the effectiveness of embolization. PMID- 11758351 TI - [Extracorporeal shock wave lithotripsy for upper urinary tract stones using piezoelectric shock wave lithotripsy]. AB - Between August 1999 and July 2000, 123 cases of renal stones and 52 cases of ureteral stones in 116 males and 59 females were treated with the New Piezolith 2500. The average number of sessions required for renal and ureteral stones was 2.50 and 1.48, respectively. At 3 months postoperatively, stone-free rates for renal and ureteral stones were 64.2% and 72.7%, respectively. Assessing residual stones less than 4 mm in diameter as an effective treatment outcome, the efficacy rates for renal and ureteral stones were 94.3% and 86.4%, respectively. Side effects were encountered in 5 cases (2.9%) of high fever and one case (0.57%) of renal subcapsular hematoma. New Piezolith 2500 is effective and safe for the treatment of upper urinary stones. PMID- 11758352 TI - [Clinical experience of in situ extracorporeal shock wave lithotripsy using ESL 500A for bilateral ureteral stones and ureteral stones in a solitary, or a functionally solitary kidney]. AB - Extracorporeal shock wave lithotripsy (ESWL) using ESL-500A was performed for the treatment of 18 cases of bilateral ureteral stones and 3 cases of a solitary or a functionally solitary kidney with ureteral stones from September 1991 to February 2000. Sixteen cases of the former and all 3 cases of the latter were treated by in situ ESWL, and the other 2 cases of bilateral ureteral stones were treated with auxiliary procedures. No residual stones were observed in any cases except for one of bilateral ureteral stones treated by in situ ESWL. The results show that in situ ESWL using ESL-500A seems to be useful for the treatment of bilateral ureteral stones and ureteral stones in a solitary kidney, including a functionally solitary kidney. However, auxiliary treatment will be needed in cases of urinary tract infection, undetectable stones by ultrasonography, or bilateral large stones. PMID- 11758353 TI - [Renal cell carcinoma in the Birt-Hogg-Dube syndrome: report of a case]. AB - Birt-Hogg-Dube (BHD) syndrome is a rare dermatological condition appearing with an autosomal dominant mode of inheritance. It was first reported in 1977 by Birt et al. and 28 cases have been reported since then. BHD syndrome is characterized by asymptomatic dome-shaped, skin-colored papules on the face and upper trunk. Recently, various neoplasms have been reported to associate with BHD syndrome, including three familial and one sporadic cases of renal tumors. We report another sporadic case with renal tumor. A 53-year-old woman complained of gross hematuria and visited our institute on November 1996. She visited the Department of Dermatology, Wakayama Medical College because of skin lesions on the face and upper trunk at her age of 44. These skin lesions were present since her mid twenties. Her daughter also had similar skin lesions and visited the same Department. There was no family history of renal tumor. The patient was diagnosed to have a right renal tumor, and radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma, papillary type. She underwent interferon injection therapy postoperatively, but died because of lung metastases on April 1997. This is the first reported case of renal tumor occurring in BHD syndrome in Japan. PMID- 11758354 TI - [A case of bilateral synchronous renal cell carcinoma treated with left partial nephrectomy and laparoscopic right nephrectomy]. AB - We describe a case of bilateral synchronous renal cell carcinoma. A 70-year-old female was admitted to our department because of further examination for bilateral renal masses. Computed tomographic scanning and ultrasound examinations revealed bilateral solid enhanced renal masses, and bilateral renal cell carcinomas were suspected. First, partial left nephrectomy was performed. On the 21th day after the first operation, we confirmed the recovery of the left kidney, and performed right nephrectomy laparoscopically. The histopathological diagnosis revealed bilateral renal cell carcinomas. The patient is alive with no metastatic lesions and no recurrence at 16 months after the operations. PMID- 11758355 TI - [Malignant fibrous histiocytoma originating in a renal capsule: a case report]. AB - We report a case of malignant fibrous histiocytoma originating in a renal capsule. A 43-year-old woman was admitted with a chief complaint of right lower abdominal pain. Physical examination was unremarkable. Serum C-reactive protein and erythrocyte sedimentation rate increased to 3.8 mg/dl and 60 mm/hr., respectively. Computed tomography (CT) and magnetic resonance image (MRI) showed a heterogeneous enhanced mass, 4 x 9 x 13 cm in size, in contact with the lateral part of the right kidney. Selective right renal arteriography revealed a hypovascular tumor, the main feeding artery of which was the right adrenal artery. Preoperative clinical diagnosis was a retroperitoneal sarcoma and transabdominal tumor resection was performed. The adhesion between the tumor and the right kidney was so severe that right nephrectomy was also necessary for a radical surgery. The tumor, measuring 13 x 9 x 6 cm, was located laterally adhering to the right renal capsule. Microscopic examination of the tumor demonstrated spindle-shaped fibroblast-like cells arranged in a storiform pattern with fibrous stroma and clusters of rounded histiocyte-like cells and pleomorphic giant cells with bizarre nuclei. Histopathological diagnosis was malignant fibrous histiocytoma arising from the renal capsule and there was no tumor invasion to renal parenchyma. No adjuvant therapy was performed but she has remained well for 31 months since the operation without evidence of disease. PMID- 11758356 TI - [Transcatheter arterial embolization of aneurysmal-type renal arteriovenous fistula: a case report]. AB - We report a case of aneurysmal-type renal arteriovenous fistula, which was successfully treated with transcatheter arterial embolization (TAE). A 73-year old woman was referred to our hospital because of an incidental abnormal renal mass detected by computed tomography (CT). CT scan showed a round mass (4 x 3 x 3 cm) in the right kidney. Magnetic resonance (MR)-angiography and angiography revealed an aneurysmal type renal arteriovenous fistula (AVF). The patient was treated with TAE using detachable coils. CT, MR-angiography and angiography are useful means for the diagnosis of renal arteriovenous fistula. TAE is a powerful treatment for renal arteriovenous fistula. PMID- 11758357 TI - Spontaneous peripelvic extravasation secondary to ovarian cyst: a case report. AB - We present a case of spontaneous peripelvic extravasation caused by ureteral obstruction secondary to an ovarian cyst. A 47-year-old woman with lower abdominal pain visited our emergency clinic. Emergency computed tomographic scan revealed extravasation around the left kidney and a left ovarian cyst. She was diagnosed to have spontaneous peripelvic extravasation by retrograde pyelography. A double pigtail stent was placed and the ovarian cyst was removed surgically. Intravenous pyelography performed after removal of the stent revealed neither urinary extravasation nor obstruction. PMID- 11758358 TI - [Recurrence of vesicoureteral reflux detected 19 years after ureterocystoneostomy: a case report]. AB - A 21-year-old male, who had been operated on for bilateral vesicoureteral refluxes (VURs) with bilateral ureterocystoneostomy (Politano-Leadbetter's method) 19 years before, was admitted to our hospital due to recurrent VUR. Since the former operation, he had undergone voiding cystography (VCUG) twice for two years, and no refluxes were found. Moreover, no evidence of upper urinary tract deterioration was found by either intravenous pyelography (IVP) or renal ultrasound scanning taken the year before this admission. Nineteen years after the operation, the dilation of the left lower ureter was found on IVP and, consequently, he suffered from pyelonephritis. The VCUG revealed the recurrence of left VUR. Because of his allergic reaction to collagen, we again performed left ureterocystoneostomy (Politano-Leadbetter's method). At three months postoperatively, there was no VUR found on VCUG. PMID- 11758359 TI - [Small cell carcinoma of the urinary bladder: a case report]. AB - We report a case of small cell carcinoma of the urinary bladder. A 60-year-old man with microscopic hematuria was referred to our hospital. Cystoscopy revealed a sessile tumor on the left lateral wall of the urinary bladder. The patient underwent transurethral resection of the bladder tumor (TUR-Bt). Because of muscle invasion (pT2), total cystectomy was recommended, but was not performed because the patient would not give consent for the operation. Six months after TUR-Bt, invasive bladder tumor recurred and total cystectomy was performed. Pathological examination of the operative specimen revealed small cell carcinoma. Adjuvant combined therapy of irradiation and chemotherapy (nedaplatin and etoposide) was ineffective. Metastases to retroperitoneal lymph nodes, lung and liver were detected soon after the adjuvant therapy. The patient died 15 months after his first visit to our hospital. PMID- 11758360 TI - [Late metastases of prostatic adenocarcinoma to urinary bladder after radical prostatectomy: a case report]. AB - We report a case of metastasis of prostatic cancer to urinary bladder. A 67-year old man was admitted with a complaint of macroscopic hematuria, who had undergone radical prostatectomy and surgical castration for prostatic cancer (pT3N0M0) 53 months before. Computed tomographic (CT) scan revealed an invasive tumor on the right wall of the urinary bladder and swelling of paraaortic and pelvic lymph node metastases. These lesions were diagnosed as bladder tumor with lymph node metastases, and then transurethral biopsy of bladder tumor was performed. Because macroscopic hematuria could not be controlled and severe progressive anemia was found after the biopsy, simple cystectomy and bilateral cutaneoureterostomy were performed on the next day. Histopathological analysis showed that the tumor was adenocarcinoma, which was thought to be a metastatic tumor from the prostatic cancer. PMID- 11758361 TI - [A case of papillary adenocarcinoma of the prostate which was difficult to diagnose]. AB - We report a case of papillary adenocarcinoma of the prostate found by urethroscopy. An 84-year-old male visited our hospital complaining of initial hematuria in July 1997. No abnormal findings were detected despite repeated urological examinations until endoscopic examination revealed fine papillary tumors in the prostatic urethra along with benign prostatic hyperplasia-like prominent left lobe of the prostate in June 2000. Serum prostate specific antigen (PSA) level was 4.1 ng/ml. He underwent transurethral resection of the urethral tumors and the prominent lobe, which was found to contain packed papillary tumors. Both of these tumors were well differentiated papillary adenocarcinoma most likely originating from the prostate because PSA immunostaining was positive. The prostate was irradiated postoperatively. Papillary adenocarcinoma localized in the prostate is difficult to diagnose preoperatively. PMID- 11758362 TI - [Prostatic carcinoma presenting as neck lymph node metastases: report of two cases]. AB - We report two cases of prostatic carcinoma presenting as neck lymph node metastases. Case 1: A 56-year-old man was admitted to our hospital with the chief complaint of left lower abdominal pain. A lymph node was palpable on the left side of the neck swollen. Rectal examinations revealed prostatic stony-hard mass. Computed tomography showed a swollen neck and paraaortic lymph nodes on the left side. PSA level was 380 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma, and neck lymph node biopsy also revealed metastatic adenocarcinoma. We diagnosed him with prostatic carcinoma stage D2 (LYM). He underwent hormonal therapy (TAB) but died 13 months later. Case 2: A 66 year-old man was admitted to our hospital with the chief complaint of a large palpable mass on the left side of the neck. Resection of this mass revealed metastatic adenocarcinoma. Rectal examination revealed no malignant lesions, but the PSA level was high, 1,700 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma. Computed tomography revealed paraaortic and pelvic lymph node metastases and bone scintigram revealed abnormal uptake, bone metastases. We diagnosed him with prostatic carcinoma stage D2 (LYM OSS). We performed bilateral testectomy followed by hormonal therapy (TAB). The lymph node metastases disappeared after 4 months of therapy. PMID- 11758363 TI - [A case of ileal conduit stenosis 13 years after construction]. AB - A 63-year-old male was admitted to our hospital with the complaint of bilateral hydronephroses. Total cystectomy and ileal conduit construction were performed because of bladder tumor (TCC, G2, pT2N0M0) in 1985. The patient remained asymptomatic, but bilateral hydronephroses was observed by ultrasonography in 1997. DTPA renogram showed the delayed excretion. Conduitgraphy and antegrade pyelography revealed that the conduit was narrow like a pinhole at 2 cm distal region from the anastomotic site of the urinary duct. The stenotic region was inflated by a 24 Fr inflation-balloon-catheter. Chronic inflammation, which was thought to be caused by infection, was detected at the stenotic conduit by biopsy. Hydronephroses disappeared after the operation and the postoperative course was uneventful. PMID- 11758364 TI - [Statistics on operations at the Department of Urology, Tatebayashi-Kosei Hospital during a ten-year period (June 1990-May 2000)]. AB - A clinical statistic survey was made on the operations performed at the department of urology, Tatebayashi-Kosei Hospital between June 1990 and May 2000. The total number of operations was 2,680, consisting of 217 operations of the kidney, 126 operations of the ureter, 454 operations of the bladder, 1,354 operations of the prostate, 186 operations of the penis and ureter, 305 operations of the scrotum, 16 urologic operations performed by laparoscopy and 22 other operations. PMID- 11758365 TI - [Carbon equilibrium in Larix gmelinii forest and impact of global change on it]. AB - In order to provide a methodological demonstration for the study of C cycle in forest, the CENTURY model was applied to simulate the C cycle in Larix gmelinii forest and to approach the impact of global change on it. The results showed that the Larix gmelinii forest served as a C sink, with an annual net absorption of 2.65t.hm-2. Climate change and increased atmospheric CO2 concentration benefited for the net primary production (CNPP) and net C absorption capacity of forests in North China. When the atmospheric temperature was increased by 2 degrees C, the gross biomass and NPP of Larix gmelinii forest increased, while soil C content decreased, and the variation of these three indices was bigger when the precipitation was decreased by 20% than increased by 20%, indicating that the limiting factor for the forest growth in this area is atmospheric temperature, while precipitation is abundant or even too much. PMID- 11758366 TI - [Gap formation features of humid evergreen broad-leaved forest in central subtropical Wawushan Mountain, Sichuan Province, China]. AB - The primary and secondary subtropical evergreen broad-leaved forests at an altitude of 1720-1750 m in Mt. Wawushan National Forest Park, southwestern China investigated to analyze their canopy gap formation characteristics. The sampling method and canopy formation causes were also discussed. In secondary evergreen broad-leaved forest, the gap density was surprisingly only 9 per hm2 and the size of all gaps was, no more than 10 m2. Almost every gap had only one gap maker, and the gap makers often died standing by suppression. Accordingly successful natural regeneration is difficult in small gap, due to the rapidly lateral growth of canopy trees. In primary evergreen broad-leaved forest, the gap density was 15 per hm2, and 56% of the gaps had an area of no more than 40 m2. The largest gap had an area of 256 m2. The canopy gap accounted for 11.1% and expended gap occupied 19.8% of land area in the forest. Median area of canopy gaps and expended gaps was 59 and 105 m2, respectively. Most gaps had more than one gap maker, and gap makers died falling and were often from mortality events separated in time. Most gaps aged over 10 yr and a few were formed recently and the estimated gap formation rate was 0.01 per year. According to falling direction of trees and the relations with growth process, slope aspect and wind, we deduced gap-maker death resulted from integrated influence among topography, climate particular in wind, tree growth characteristics, and interactions of population under competition. Adapting method of plot sampling and projection drawing used in the paper can improve investigation accuracy and help improving comparison of results in different investigation area. PMID- 11758367 TI - [AFLP analysis on genetic structure of planted Acacia auriculiformis population in Heshan]. AB - AFLP analysis of Acacia auriculiformis populations in 3 different planted communities with the same provenance and same planting time indicated that the genetic heterozygosity was quite high in the plantation population. 90.73% of total genetic variance distributed within a population, while only 9.27% among populations. The most distinct genetic structural difference was found between pure plantation and legume mixed plantation, next was between legume and non legume mixed plantation, and the most similar was between pure and non-legume mixed plantation, which revealed that the genetic variation in this Acacia auriculiformis population was relatively higher than that from the natural forests by isoenzymic analysis data. The genetic differentiation was not the result of gene flow, but the result of the artificial selection and the microenvironmental changes. PMID- 11758368 TI - [A preliminary study on ecological response of dominant tree species in Korean pine broadleaf forest at Changbai Mountain to soil water stress and their biomass allocation]. AB - Pot culture experiments were conducted to examine the ecological response and biomass allocation of Pinus koraienes, Fraxinus mandshurica, Juglans mandshurica, Tilia amurensis, and Quercus mongolica. The five dominant species in the Korean pine-broadleaf forest at Changbai mountain. Their seedlings were grown under three different soil moistures, e.g., 85%-100% (CK), 65%-85% (MW) and 45%-65% (LW) of field water-holding capacity. The results showed that drought significantly decreased the individual leaf area, number of fine root, root length, and individual biomass of seedlings. The root proportions of T. amurensis and F. mandshurica increased with increasing soil water content, but the leaf proportion of J. mandshurica and Q. mongolica in MW treatment was higher than that of CK and LW. There was no significant difference in stem proportions of 5 tree species among different water stress treatments. The response of the biomass of 5 tree species to water stress was significant, the total biomass of T. amurensis, F. mandshurica, J. mandshurica and P. koraienes in MW and LW decreased by 32.8%, 43.6%, 26.2% and 23.8%, respectively, while that in Q. mongolica increased by 4.8%, indicating that Q. mogolica was the most drought-tolerent species among 5 tested species. PMID- 11758369 TI - [Decomposition processes of Tilia amurensis leaves in the Changbai Mountain forest ecosystem]. AB - A 4-year field experiment was carried out in the Changbai Mountain to study the decomposition process of Tilia amurensis leaf and its affecting environmental factors. The results reveal that the decomposition process of Tilia amurensis leaves could be expressed by an exponent equitation. With the increase of elevation and the change of vegetation types, the decomposition rate in 1-5 standard experimental fields was -0.391, -0.339, -0.257, -0.198 and -0.125, respectively, indicating that the decomposition rate was decreased with ascending elevation. The maximum decomposition took place when the environment was in the shadow of 60%-80%. The leaves were acceleratively decomposed when the tested moisture was increased. Moisture affected the decomposition process more strongly than light. PMID- 11758370 TI - [Influence of temperature and moisture on soil nitrogen mineralization under two types of forest in Changbai Mountain]. AB - The effect of temperature(t) and soil water content(theta) on soil nitrogen mineralization under coniferous-broadleaved and spruce-fir coniferous forests was evaluated by using laboratory incubation method. Based on the analysis of inorganic nitrogen in soil extracts before and after incubation, it was showed that the net mineralization rate of soil nitrogen was positively related to t(alpha < 0.001) from 5 degrees C to 35 degrees C, and to water content when water contents was low, but there was a decrease in net mineralization rate when the water content was above an optimum value. The result suggested the interactive effect of temperature and moisture on the mineralization of soil nitrogen. Two dimensional (t, theta) equations to describe the effect were drawn up. PMID- 11758371 TI - [Characteristics of litter and its contained water in three succession communities in Dinghushan Mountain]. AB - Studies on the characteristics of litter and its contained water in three succession communities in Dinghushan Mountain showed that the standing mass of litter was in the order of pine forest > mixed forest > broad-leaved forest, and the annual litterfall was broad-leaved forest > mixed forest > pine forest, indicating that the return rate of nutrients was lower in pine forest than in broad-leaved forest. The proportion of leaf litter decreased in the order of pine forest > mixed forest > broad-leaved forest, and that of branch, flower, and fruit litter was on the contrary, because the broad-leaved forest had the largest amount of branches and the biggest scope of canopy. The staturation water content of litter in pine forest, mixed forest and broad-leaved forest was 329.0%, 313.0% and 295.0%, respectively, showing no significant difference, but the water content of litter in three communities differed significantly, followed the order of broad-leaved forest > mixed forest > pine forest. The evaporation ratio of litter water to free water in broad-leaved forest, mixed forest and pine forest was 78.9%, 82.45% and 91.22%, respectively. PMID- 11758372 TI - [Nourishing characteristic of geochemical elements in Antarctic mosses and lichens]. AB - Studies on the nourishing properties of geochemical elements in Antarctic mosses and lichens show that potassium and calcium were the most active elements, while phosphorous was accumulated in the middle part of lichen cells, and participated in organic synthesis. Mosses accumulated sulphur stressly, but took in iron and magnesium negatively. Aluminum and silicon were absorbed passively by lichens. It is concluded that potassium and calcium were the important nutrient elements for the growth of mosses and lichens, sulphur and phosphorous were the middle significant nutrients, while aluminum and silicon were the passively accumulated elements. PMID- 11758373 TI - [Characteristics and quantitative simulation of stomatal conductance of Aneurolepidium chinense]. AB - Based on field measurements of stomatal conductance and photosynthesis of Aneurolepidium chinense, the dynamic characteristics and the relationship between stomatal conductance and environmental conditions were examined to develop a leaf stomatal conductance model for A. chinense. The results showed that the variation of stomatal conductance of A. chinense was closely correlated with environmental factors, such as physiologically active radiation (PAR), vapor pressure deficit (VPD) and air temperature (Ta). The daily variation of A. chinense stomatal conductance could be described as M-type curve at fair-weather, but [symbol: see text]-type curve at cloudy weather. The value of stomatal conductance increased with the increase of PAR or Ta, but decreased with the increase of VPD. The relationship between stomatal conductance(gs) and environmental factors could be expressed as: gs = PAR(2.01 Ta2 + 147.74 Ta2321.11)/((444.62 + PAR)(-538.04 + VPD)). This model would be helpful to simulate the dynamical photosynthesis of leaf and canopy and to further simulate the NPP of ecosystems and the exchange of water and heat among the soil-plant-atmosphere continuum. PMID- 11758374 TI - [Distribution characteristics and seasonal dynamics of phosphorus and potassium in wetland ecosystem in the Sanjiang Plain]. AB - From May to October in 1997, the plant, soil and logging water in the wetlands were sampled monthly, and their P and K concentrations were measured. With the method of one-factor non-linear regression analysis, the seasonal dynamics of P and K in two types of wetland i.e., in Carex lasiocarpa-Glyceria spiculosa wetland and in Deyeuxia angustifolia wetland were studied. The concentrations of P and K varied with different species of wetland plant and different organs of the same plant species. But their common property was that the concentration of K was higher than that of P, which shows that the mire-wetland plants had the property of enriching K element. The concentrations of P and K had an obvious seasonal dynamics in plant, soil and logging water, but the patterns were not the same. Some simulation models were obtained, which could be used to forecast the seasonal dynamics of P and K contents. PMID- 11758375 TI - [Effect of forest patch size and isolation on reproductive success of Great Tit in fragmented secondary-forests]. AB - The effect of forest patch size and isolation on reproductive success of Great Tit (Parus major) in fragmented secondary-forests was studied in Zuojia Natural Protection Area of Jilin Province by collecting data on breeding success, clutch size, laying date, egg weight, brood-size and number fledged of Great Tit in 18 large (20-30 hm2), medium (10-20 hm2), and small (6-10 hm2) patches, and two extensive forests (> 100 hm2). All the forest patches were GPS tested. The results showed that isolation had no effect on reproductive success of Great Tit, and Great Tit laid 7.2 days earlier in extensive forests than in all forest patches. Clutches in extensive forests and large forest patches were slightly larger than those in medium and small forest patches, and eggs were heavier in extensive forests than in the patches. Patch size had no effect on brood-size and number fledged. The lost rate of the nests was high in medium and small forest patches because of intense competition. PMID- 11758376 TI - [Spatial pattern and temporal dynamics of Atylotus pallitarsis population in Songnen Plain]. AB - The spatial pattern and its time series dynamics of Atylotus pallitarsis population were examined in this paper. The results showed that the amount of this population was closely related to temperature and humidity, and its blood peak time appeared at about 14:00 o'clock in the afternoon. The population cattle was aggregated distribution and emigration throughout the day, the aggregated distribution pattern was loose mass community, the distribution of insects in the community was at random. PMID- 11758377 TI - [Characteristics and distribution pattern of farmland patch in river valley in middle and low Taihang mountain area--a case study in Yanzhi River in Fuping County, Hebei Province]. AB - Based on the investigations in the main valley of Yanzhi river in Fuping county of Hebei Province, the characteristics and distribution patterns were analyzed. The results indicated that farmland patches were distributed in the whole valley, except the headstream reach. With the increase of human disturbances, the proportion of farmlands increased along the river from upstream to downstream, while in natural landscapes, the environmental heterogeneity and fragmentation of farmlands decreased. The area of Yanzhi river valley totaled 2297.09 hm2, mainly composed by farmland. There were 117 farmland patches mainly distributed along the riverbank in the valley, totalling 1027.78 hm2 and occupying 44.74% of the valley, which were very well irrigated, but always endangered by flood. The farmland patches were not symmetrically distributed along river, with 57.17% of farmland located on the left side of bank. The width of farmland patch presented an increasing trend, with a remarkable variation. The farmland patches were mainly strip-shape. PMID- 11758378 TI - [Enrichment of organic matter and nitrogen in eroded bedloads]. AB - Under natural rainfall, the influences of rainfall, slope gradient, tillage and fertilization on the enrichment ratio(ER) of organic matter(OM) and total nitrogen(TN) in eroded bedloads and the relationship between the ER and the composition of eroded bedloads was analyzed. The results showed that the enrichment of clay(ERclay) resulted in the enrichment of OM and TN, and the average value of ERclay, EROM and ERTN under different slope gradients was 1.77, 2.09 and 1.61, respectively. The soil erosion module was negatively correlated with EROM and ERTN. The measures for soil erosion may increase the EROM and ERTN affected by rainfall, slope gradient, tillage and fertilization. PMID- 11758379 TI - [Influence of rare earth elements on chemical transformation of nitrogen in agricultural soil]. AB - Soil available N, NH4(+)-N and NO3(-)-N contents and soil urease activity were measured after application of rave earth elements(REEs). The results showed that the contents of soil available N and NH4(+)-N were affected by application of REEs, being significantly differed from those in the control when the dosage was higher than 5 mg.kg-1 dry soil. However, soil NO3(-)-N content in treated plots did not differed from that in the control. No observed effect concentration (NOEC) for the potential influence of REEs on the chemical transformation and availability of soil available nitrogen was found to be 5 mg.kg-1 dry soil. The decrease of soil available N concentration was found closely correlated to the inhibition of soil urease activity (R2 = 0.87). It was suggested that the inhibition effect of REEs on the enzymatic nitrogen mineralization should be one of the major causes for the decline of soil available nitrogen concentration. The decrease of available nitrogen concentration occurred shortly after REEs application, indicating that there should be a self-regulation process to maintain the available nitrogen concentration in soil. PMID- 11758380 TI - [Indexing system and its quantitative expression for soil quality evaluation in Hainan Island]. AB - Based on the SOTER database and some FAO frameworks, a soil quality indexing system was established, and some evaluation results were presented for some selected GIS photo spot of tropical cropland in Hainan island. With connection to the spatial database, this system could perform the output of evaluation results. The performance and evaluation results were approved by the local expertise. It is suggested that the established models should be modified by the local practice. PMID- 11758381 TI - [Effect of different tillage methods on rice growth and soil ecology]. AB - Field experiments were conducted in double-cropping rice field in South China during 1998-1999 to study the effect of different tillage methods on rice growth and soil ecology. The results showed that with rice scattering planting, no tillage method caused a reduction of rice tillering, effective panicle, and filled grains of rice. Grain yield under no-tillage was 13.40% lower than that under conventional tillage, and the economic benefits decreased by 10.9%. Soil analysis showed that in no-tillage fields, soil bulk density and hardness were increased, soil porosity and available P and K were decreased, the amount of actinomyces and fungi was reduced, while that of soil bacteria was increased, and the enzyme activity was promoted. Minimum tillage and conventional tillage had similar soil physical and chemical properties, soil microbial quantity and enzyme activity. Minimum tillage could produce a 2.1% higher grain yield than conventional tillage, and increase the economic benefits by 11.0%. PMID- 11758382 TI - [Effect of HCO3- on root growth and nutrient absorption of different rice genotypes]. AB - Solution culture experiments with Zn-inefficient cultivar (IR26) and the Zn efficient cultivar (IR8192-31-2) were conducted to study the effect of HCO3- on the root growth and nutrient absorption of different rice cultivars. The results showed that HCO3- strongly inhibited the root growth of Zn-inefficient cultivar especially at low Zn concentration. In contrast, that of Zn-efficient cultivar was slightly stimulated by HCO3- at low Zn concentration. HCO3- not only inhibited Zn absorption of Zn-inefficient cultivar, but also inhibited its absorption of Fe, Mn, Cu, implying that there was no specific inhibition of HCO3- on Zn absorption. These results demonstrated that the inhibition of root growth by HCO3- was likely to be the initial action of HCO3- in inducing Zn deficiency in lowland rice. With treatment of bicarbonate, Zn concentrations in upper and lower leaves of the Zn-efficient cultivar and their ratios were higher than those of the Zn-inefficient cultivar. The results showed that the Zn-efficient cultivar could transport more zinc from lower leaves to upper leaves, which might be-one of mechanisms that the Zn-efficient cultivar adapted to zinc deficiency in calcareous soil. PMID- 11758383 TI - [Growing degree-days requirements for plant and leaf development of summer maize (Zea mays)--an experimental and simulation study]. AB - A growing degree-day (GDD) calculation method was recommended by comparing several popular used GDD calculation equations. The GDD between different development stages, from emergence to each leaf appearance and during the lifetime of each leaf, were calculated for summer maize with the field treatments differed in cultivars, plant density, sowing dates, water and fertilizer supplying levels. Factors influencing the stability of GDD were discussed, and simulation equations to predict the leaf development were fitted based on the field observed data. PMID- 11758384 TI - [Changes of photosynthetic characteristics of strawberry leaf under shading]. AB - Studies on the photosynthetic characteristics of two strawberry varieties (Baojiaozaosheng and Shuofeng) under shading showed that the photosynthesis rate decreased by 20% and 47%, when the apparent quantum efficiency increased by 13% and 8%, respectively. The chlorophyll content was enhanced slightly, while the insoluble protein content in leaf decreased drastically. The results also showed that the PSII activity decreased by 22.5% and 53.7%, and the activity of Rubisco, the key enzyme of Calvin cycle, decreased by 19.6% and 35.5%, respectively. The reason of photosynthesis rate descent in light saturation point was also discussed. PMID- 11758385 TI - [Effect of long-term single application of chemical fertilizer on soil properties and crop yield]. AB - A long-term located experiment showed that single application of chemical fertilizer basically sustained the quantity level of soil organic matter, nitrogen and phosphorous, reduced the energy level of soil humus and enhanced its condensation degree, aromaticity and aging function. The corp yield was basically the same as that of combined application with organic manure. PMID- 11758386 TI - [Influence of fertilization depth on root system senescence of upland wheat after anthesis]. AB - A soil column study showed that fertilization in a depth of 20-40 cm sustained the activities of superoxide dismatase (SOD) and catalase (CAT) in root system at a high level, meanwhile the root system vigor, the soluble protein content in root system decreased slowly, and the content of malondiadehyde (MDA) in wheat root system decreased, which delayed its senescence. It is considered that the depth (20-40 cm) of fertilization could be used as an index for delaying senescence. PMID- 11758387 TI - [Arthropod community structures in transgenic Bt cotton fields]. AB - Arthropod community structures were investigated in transgenic Bt cultivars, Bollgard(B) and Chinese cotton 30 (CC30), and common cultivars, control (C) and no control (NC) cotton field in North China in 1998. The results showed that compared with common cultivars, the species richness and the number of total individual of arthropod community in transgenic Bt cultivars field were reduced 2.4-16.3% and 71.0-78.3% respectively, in which dominant species in phytophagous subcommunity varied. The number of individual of predatory and parastic subcommunity were all increased. The similarity coefficient between CC30 and NC was 0.8243, B and NC 0.7320, B and C 0.3380, C and NC 0.3128, CC30 and C 0.2665. The order of diversity and evenness value of these were CC30 (2.3712 and 0.6428), NC (2.3654 and 0.6251), B (2.1364 and 0.5791), and C (1.0877 and 0.2949), their dominant value was 0.8726 (C), 0.3528(B), 0.1178(NC) and 0.1048 (CC30) respectively. It was concluded that different integrated pest management (IPM) strategy should be implemented in transgenic Bt cotton instead of common variety cotton field. PMID- 11758388 TI - [Effects of volatiles from different trophic level on foraging behavior of Aphidius avenae]. AB - The responses of female Aphidius avenae to volatiles from undamaged wheat plant, Sitobion avenae and Rhopalosiphum padi, aphids-plant complexes and aphids damaged plant were investigated in wind tunnel and Y-tube olfactometer. The volatiles from undamaged wheat plant, S. avenae and R. padi were much less attractive to A. avenae than those from aphids-plant complexes and aphids-damaged plant. Although the parasitic rate was much lower, the R. padi-plant complexes and R. padi damaged plant were also attractive to A. avenae. Identification of volatiles by GC-MS showed that the main volatiles induced by aphids feeding were 2-camphene, 6 methyl-5-hepten-2-one, 6-methyl-5-hepten-2-ol, Z-3-hexenyl-acetate, and methyl salicylate, among which, 6-methyl-5-hepten-2-one and 6-methyl-5-hepten-2-ol were more attractive to A. avenae, while methyl salicylate was not attractive. PMID- 11758389 TI - [Influence of temperature and relative humidity on epizootiological features of Zoophthora anhuiensis in Myzus persicae colonies]. AB - The colony of green peach aphid, Myzus persicae(Sulzer), which was initiated with 3 pathogen-free apterae and another 3 ones inoculated with the conidia of the entomophthoraceous fungus, Zoophthora anhuiensis(Li) Humber, was maintained on detached cabbage leaves at the regimes of 10-25 degrees C and 90-100% of relative humidity(RH), and allowed for free reproduction and fungal infection. Based on 26 day observations, it was showed that the development of Z. anhuiensis in the colony was rapid at 15 or 10 degrees C, regardless of the humidity range concerned. The cumulative mortality of the aphids attributed to Z. anhuiensis infection was 72.9-98.2% at 10 degrees C on day 26, and 78.7-94.4% at 15 degrees C on day 24, indicating the occurrence of epizootic in the colony. At 20 degrees C, a high-level epizootic occurred only at 100% RH, with a cumulative mortality of 71.6% on day 24, contrasting to a much lower mortality (5.1-12.8%) at the other three humidity regimes. However, the maximal mortality at 25 degrees C on day 20 was only 27.2% even at 100% RH. Obviously, Z. anhuiensis caused aphid epizootic more easily at lower temperature, and to less degree was affected by the humidity. The disease prevalence (represented by the cumulative mortality) was correlated well to temperature, its interaction with relative humidity, and the days from initiation (r2 = 0.82, alpha < 0.01). PMID- 11758390 TI - [Ecological engineering for eutrophication control in lake]. AB - An ecological engineering was conducted for eutrophication control in the Nanhu Lake of Changchun. In 1996, the removal of phosphorus by harvesting aquatic macrophytes and fishes was 149.6 kg and 189.9 kg, respectively, and the phosphorus fixed in molluscs was 153.4 kg. The total output was 492.9 kg, which amounted approximately to the annual phosphorus input to the lake. After ecological engineering, the water quality turned better, the TP concentration in lake water decreased, the phytoplankton density reduced, and the number of phytoplankton species increased. The roles of molluscs and fish in controlling lake eutrophication should be further studied. Ecological engineering is an ideal method to control the eutrophication of urban lakes. PMID- 11758391 TI - [Effect of VAM fungi on phosphatase activity in maize rhizosphere]. AB - The effect of VAM fungi on phosphatase activity in maize rhizosphere was examined by pot culture experiment, in which, three-compartment-pots were used, the central compartment being separated from the outer two by a nylon net with 30 microns mesh. Plants were harvested 70 days after planting. Soil acid and alkaline phosphatase were measured at different distances from root surface. The results showed that VAM increased the activities of soil acid and alkaline phosphatase in the rhizosphere. It was found that different phosphorous sources had different effects on phosphatase activity. PMID- 11758392 TI - [Diversity of Sinorhizobium fredii strains]. AB - Rhizobial strains were isolated from soils growing with soybean cultivar Heilong 33 and Willimas. Fifty Sinorhizobium fredii strains were chosen, and their biological characteristics including growth velocity, acid-alkali endurance, resistance of intrinsic antibiotics, utilization of carbon and nitrogen sources, absorption of congo red, ability of melanin production, and plasmid profiles were comparatively researched. The dendrogram was described using the method of cluster analysis, and the biodiversity of Sinorhizobium fredii from different soils was proved. PMID- 11758393 TI - [Land degradation and landscape ecological construction in Liaoning Province]. AB - The degradation degree, area and distribution of three types of degraded land caused by erosion, desertification and salinization were investigated in Liaoning Province by using landsat TM 1:250,000 and GIS Data. The area of eroded, desertificated and salinized land occupied 92.5%, 3.39% and 2.22% of the total provincial land area, respectively. Therefore, the land in this province was classified into three degradation regions: contemporary erosion degradation, geological erosion degradation, and desertification and salinization degradation region. The characteristics and the cause of degradation for each region were also analyzed. According to the local situation and the theory of landscape ecology, some landscape construction and restoration models were proposed. PMID- 11758394 TI - [Landscape dynamics of two-side lands-along main urban roads in southwestern Shanghai]. AB - Based on the aerial photos of Shanghai in 1984, 1989 and 1994, the landscape databank of southwestern Shanghai was set up. According to the analysis of the landscape dynamics of three two-side belts along the main urban roads in southwestern Shanghai, it was showed that there was a great difference in the landscape succession of these belts with various functions. The main urban roads trended to multi-serving function with the expansion of the city. The change from increase to decrease in the diversity and evenness of landscape and the decline in landscape fragmentation were the major symbols of the landscape dynamics. PMID- 11758395 TI - [Effect of Shajiang black soil amended by coal fly ash on ecological factors and residue of heavy metal in wheat field]. AB - The effect of Shajiang black soil amended by coal fly ash on ecological factors in wheat field and residua of Cd, Cr, Pb, Hg and As were studied by pot experiment. The results showed that applying coal fly ash into Shajiang black soil could decrease soil density, soil proportion and clay content, but increase soil porosity, filtration coefficient and soil temperature. Moreover, it could promote water evaporating when soil moisture was high and keep soil water when lower than 10%. It also could facilitate activity of soil micro-organism and promote soil nutrient transforming. With (6-18) x 10(4) kg.hm-2 coal fly ash applied in Shajiang black soil, the accumulated quantity of Cd, Cr, Pb, Hg and As in soil and in wheat grain were lower than international standard index of pollution. Therefor, Shajiang black soil amended by coal fly ash was safe and reliable within the above range. PMID- 11758396 TI - [A comparative study on the sensitivity and specificity of cholinesterase and glutathione s-transferase in Gammarus pulex L]. AB - Studies on the influences of lindane, pirimiphos methyl, permethrin, zinc and dodecyl linear alkybenzene sulfonate (LAS) on the activity and toxicity of cholinesterase (ChE) and glutathione s-transferase (GST) in Gammarus pulex L. showed that only pirimiphos methyl caused a change in ChE activity in Gammarus, with a significant reduction in enzyme activity after 24 h and 48 h exposure. Both lindane and permethrin caused a change in GST activity in Gammarus, with a significant increase in enzyme activity after 48 h exposure. Lindane alos caused a significant increase in GST activity after 24 h exposure. Biomarkers ChE and GST were demonstrated a high degree of specificity and sensitivity in comparison to the lethality assay, but GST activity was less specific than ChE activity. PMID- 11758397 TI - [Effect of organic acids on soil chemical behavior of lead and cadmium and their toxicity to plants]. AB - The interaction between organic acids (citric and oxalic acids) and heavy metals was examined in this paper. Equilibrium dialysis showed that the extent organic acids bound metals depended on the metal involved, and their binding properties affected the adsorption of Pb and Cd by soil, which was increased in the presence of oxalic acid, and decreased in the presence of citric acid. The effect of citric acid on the behavior and toxicity of Pb and Cd to plants was also studied. The presence of citric acid could reduce the toxicity of Pb, and inhibit the uptake of Cd in shoots and roots. However, there was no significant effect on the apparent toxicity of Cd. The interaction between Pb and Cd was found to be complicated. The Pb content in rice was higher in the presence of Cd, while the content of Cd is lower in the presence of Pb. PMID- 11758398 TI - [Relationships between soil-plant nutrition, quality of agricultural products and human and livestock health]. AB - The abundant and insufficient situation of essential elements such as calcium magnesium, sulphur, zinc and iron and beneficial elements such as selenium and iodine in soils was reviewed, and the influences of these elements and organic matter on the quality of agricultural products and human and livestock health were discussed. The trends of future research in the field of soil element science and plant nutrition, in particular, the quality of agricultural products were prospected. PMID- 11758399 TI - [Assessment of ecosystem health--concept framework and indicator selection]. AB - Based on the concept framework of ecosystem health, this paper discussed the suitable indicators to synthetically assess the ecosystem health in governed landscape. Healthy ecosystem means not only ecological health itself, but also the long-term maintenance of healthy human population and the beneficial promotion of social and economic development. Resilience, biodiversity and productivity are the characteristics of healthy ecosystem. The first step in the structure of indicators to assess ecosystem health should be the determination of precise indicator principles. According to the purpose of assessment and the principles of selecting indicator, the indicator system for assessing ecosystem health can be divided into three categories, namely, biophysical indicators, ecological indicators, and social and economic indicators. PMID- 11758400 TI - [Gene dispersal risk of transgenic plants]. AB - Gene flow is a key problem and top topic in risk assessment and management of transgenic plants. Five major study areas of gene dispersal in transgenic plants were reviewed in this paper, which include gene flow from transgenic plant to its wild species, characteristics of gene flow based on pollen, methods of doing experiment and risk assessment for gene flow, safety standards of risk assessment of transgenic plants, and long-term ecological impact of gene flow in the future. Some areas needed to be studied further were also proposed. PMID- 11758401 TI - [Allelopathy in sustainable development of agriculture]. AB - Allelopathy in agriculture was summarized. For sustainable development of agriculture, inhibitions and simulations of allelopathy as some new measures were put forward and suggested to apply reasonably and effectively, so as to improve some techniques about crop straws returning into soil, cultivation measure, crop rotation and bio-control of weeds and insect pests. PMID- 11758402 TI - [Degradation of phenanthrene and pyrene in contaminated soil by immobilized Zoogloea sp. and Fusarium sp]. AB - Immobilized with PVA, sodium alginate and activated carbon, both Zoogloea sp. and Fusarium sp. strains could degrade phenanthrene and pyrene efficiently. The optimal carrier was made of 100 rho.g-1 L PVA, 5 sodium alginate rho.g-1 L and 50 activated carbon rho.g-1 L. The degradation rates of phenanthrene and pyrene in 10 days were 87.48% and 75.34% by the immobilized bacterium, 37.04% and 20.85% higher than those by the free bacterium, and the rates in 15 days were 84.36% and 74.87% by the immobilized fungus, 5.35% and 11.23% higher than those by the free fungus. PMID- 11758403 TI - [Effect of pH on nodulation of soybean rhizobia from Weifang and Huayuankou soils]. AB - The effect of pH on the nodulation of Sinorhizobium fredii and Bradyrhizobium japonicum was examined by analyzing the indigent soybean rhizobia, predominant indigent rhizobia, and specific rhizobia, respectively. The results showed that very acid and very alkaline environment could retard the nodulation and inhibit the growth of the rhizobia. Sinorhizohium fredii could endure environment more strongly than Bradyrhizobium japonicum, and had a high competitive nodulation capacity. Bradyhizobium japonicum could endure acid environment more strongly than Sinorhizobium fredii. In very acid and very alkaline environment, the nodulation capacity of S. fredii and B. japonicum was mainly determined by their physiological characteristics. PMID- 11758404 TI - [Decomposition interaction of mixed litter between Chinese fir and various accompanying plant species]. AB - Studies on the decomposition of mixed litter between Chinese fir and 8 accompanying plant species showed that the decomposition of Chinese fir litter was promoted to different degrees by 8 mixed plant species, in which Angiopteris fokiensis had the greatest effect, while Schima superba had certain promotion first, but then, weak inhibition. The order of promotion was Angiopteris fokiensis > Maesa japonica > Ficus simplicissima > Woodwardia japonica > Boehmeria nivea > Castanopsis fargesii > Castanopsis fissa > Dicranopteris dicotoma. Chinese fir litter had a certain inhibition to litter decomposition of Schima superba and Castanopsis fissa, and certain promotion to litter decomposition of Castanopsis fargesii, but the interactions were not significant. There existed an interaction between Chinese fir and some plant species in the course of mixed decomposition. Therefore, rational protection and restoration of understory plant was important to fasten nutrient cycling of Chinese fir plantation ecosystem and to maintain soil fertility. PMID- 11758405 TI - [Causal factors of decline disease in exotic pine (Pinus taeda and P. elliottii) plantations]. AB - Investigation on the cause of the decline of exotic pine plantations in Anhui Province was carried out from 1995 to 2000. The results showed that the cause might develop from the interaction of three or more sets of factors. The first group of factors called as predisposing factors were high and low temperature and rainfall, poor soil fertility, and excessive soil bulk density, soil moisture, and of stand density; the second group of factors called as inciting factors were insect defoliators, damaging diseases of needles, late spring frost, severe drought, and excessive resin-tapping, and the third group of factors called as contributing factors were several biotic agents such as shoot blight infected by Sphaeropsis sapinea, decay wood and root rot by fungi, and bark beetles and wood borers. PMID- 11758406 TI - [Relationship between decline disease of exotic pines(Pinus taeda and P. eliottii) and forest stand and environmental factors]. AB - The relationship between decline disease of exotic pines(Pinus taeda and P. eliottii) plantations in Anhui Province and forest stand status and environmental factors was quantitatively analyzed. Among 18 variable factors from 4 types of factors(climate, soil, stand status, and other diseases and insect pests), 10 factors contributed greatly to the state of illness. These were tree age, stand density, resin-tapping, rainfall, temperature, clay soil, stone soil, soil depth, water-logging, and other diseases and insect pests. Of them soil depth and rainfall negatively, and others positively related with the severity of disease. Accordingly, a linear multiple regression model was derived, which might predict the developmental level of decline disease at any given conditions of exotic pine plantation. In addition, the spiral chart of decline disease was mapped based on the action size and time order of various nosogenetic factors during the incidence of decline disease, which was used to visually describe and quantitatively analyze the disease with complicated causes. PMID- 11758407 TI - [Variation of soil microsite moisture-physical properties and its effect on Fraxinus mandshurica juvenile stand growth]. AB - Soil microsite plays an important role in the regeneration, seedling survival, and individual growth of trees. This paper studied the relationship between soil microsite moisture-physical properties and Fraxinus mandshurica growth. Variation was found not only among different sites in traditional scale, but also among different microsites. Some variations of soil properties among different microsite were greater than those among different sites. The growth of Fraxinus mandshurica varied greatly among different microsites. Microsites affected most soil moisture-physical properties and tree growth. The study demonstrated the importance of matching trees to the proper microsite on the growth of plantation stand. PMID- 11758408 TI - [Response of structural plasticity of Tilia amurensis sapling crowns to different light conditions]. AB - This paper studied the crown structure of Tilia amurensis saplings, e.g. the shape of crown, and the distribution of branch and leaf. It is shown that the crown structure of the saplings was modified plastically in response to different light conditions. The differentiation of the first order branches was promoted by strong radiation, due to the bole growth being inhibited under high light condition, whereas the bifurcation density of the first order branches whose growth was inhibited by shading was promoted in under-canopy environment. The quantitative leaf densities of the saplings obviously decreased with the decrease of light level, while their leaves tented to distribute in upper crown. The interception of the saplings was enhanced by the distribution pattern of branches and leaves in crown. Under adequate shade condition, the saplings had the strategy of shade-avoidance of pioneer species in upward growth, and had the strategy of light-forage of moderate shade tolerance in horizontal branch growth. The saplings expressed typically shade-tolerant under weak light condition. Such a change of crown structure was an advantageous adaptation for enhancing light interception. PMID- 11758409 TI - [Phenolic acid degradation fungi screened from successive plantation site of Chinese fir]. AB - Successive plantation of Chinese fir (Cunninghamia lanceolata) leads an obvious decline of soil fertility. To solve the urgent problem, five fungal species (F2, F3, F4, F7, F15) which can effectively degrade phenolic acid were screened to degrade the toxic material in successive plantation site and to improve the soil bioactivity. Pot experiment showed that all test fungus, except F4, could improve plant growth individually, but not counteract the effect of phenolic acid. Inoculating five inoculated fungi mixed with equal proportion not only counteracted the inhibitory effect of phenolic acid but also improved the growth of Chinese fir uninoculated with VAM fungi but inoculated with G. mosseae. PMID- 11758410 TI - [Age-structure dynamics and genetic consequences of Hippophea rhamnoides L. subsp sinensis clone population in Mu Su sandland]. AB - Based on the measurement of all individuals of population at different successional stage, the investigation on edge dispersal effect and the following excavation of clones, the dynamics of age structure and genetic consequences of Hippophea rhamnoides L. subsp sinensis clone population in Mu Su sandland were examined. The results showed that the age structure of the clone population was characterized by a transformation from an increasing type in the early period starting from the initial colonization through a stable type to a declining type. The clone population could maintain or recover its stability by edge dispersal and gap regeneration with clonal growth. As the population self-thinned, the composition of clone population changed from more clones with less ramets to less clones with more ramets and the genetic diversity of clone population decreased. PMID- 11758411 TI - [Relationship between growth potential of pine, population density of Monochamus alternatus and pathogenicity of Bursaphlenchus xyloophilus]. AB - The results showed that the growth potential of pine (x) is negative related to the population density of Monochamus alternatus (y) and the pathoyenecity of Bursaphlenchus xyloophilus (z). But the population density of Monochamus alternatus is positively related to the pathogenicity of Bursaphlenchus xyloophilus. Three linear equations regression line were established as y = 1793.771 - 16404.47x, z = 31.80989 - 241.9274x, y = -407.611 + 70.51478z. Correlation coefficient is -0.8139, -0.8770 and +0.9864 respectively. PMID- 11758412 TI - [Prevalent forecast of kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae]. AB - The prevalent analysis of kiwifruit bacterial canker for several years showed that the effective ecological factors of severe degree were the precipitation (x1) in the second and last ten-days of March, and the average temperature (x2) of January. The model was y = 2.1359 + 0.0107x1 - 0.6061x2. The main factor of the prevalence was the relative variation of ten-days average temperature and precipitation in Winter and in early Spring, and the regression equation was y = 8.127 + 22.739x - 13.254x2. The forecast effect of the equation was obviously significant after testing. PMID- 11758413 TI - [Ecological factors affecting prevalence of kiwifruit bacterial canker and bacteriostatic action of bacteriocides on Pseudomonas syringae pv. actinidae]. AB - According to the systematic study for 5 years, this paper dealt with the ecological factors affecting prevalence of kiwifruit bacterial canker. The disease was more serious in the orchards with above 750 m in elevation, and more serious at mountain slope facing south than facing north. Incidence differed significantly among cultivars, with easy disease infection for Jinfeng, and strong disease resistance for Jinkui. The older the trees, the more the diseased plants. The one year old twigs had highest death twig incidence of diseased twigs and death twig incidence than other twigs. Among 6 tested bacteriocides, Jiaruinong and streptomycin showed best bacteriostatic effect. PMID- 11758414 TI - [A primary study on seed production of medicinal plant Sinopodophyllum hexandrum]. AB - The study on the seed production of five Sinopodophyllum hexandrum (Berberidaceae) populations demonstrated that the average ovule number, average seed number and seed set ratio of these populations were varied, but all positively related with the altitude of the population. The average ovule number of a flower ranged from 58.79 to 87.97, average seed number of a fruit ranged from 40.02 to 80.58, and average seed set ratio of population ranged from 61.29% to 91.60%. The average weight per seed in a fruit was negatively related with the altitude and seed number in the fruit. The result also showed that seed production of a population had no obvious difference in different years. Although seed production was mainly influenced by nutrition condition of the individual, it was still influenced by altitude and other factors. Seed number in a fruit was positively related with fruit size(including weight, length and width) and total seed weight of the fruit, but average single seed weight of a fruit had no obvious relation with fruit size and total seed weight of the fruit. PMID- 11758415 TI - [Effect of grazing rate on biomass and element composition of Xanthoparmelia camtschadalis]. AB - Xanthoparmelia camtschadalis is widely distributed in grassland area of Mongolian Plateau. There are few studies on the relationships between biomass, element composition and stocking rate. The relationships of biomass and element composition of Xanthoparmelia camtschadalis to grazing rates in Leymus chinensis steppe in Inner Mongolia were investigated. The results indicated that the biomass of the lichen was highest under light grazing, while the lowest under extremely overgrazing treatment. The C, N and Ca concentrations were higher than 1%, P, Mg, K and Fe were between 0.1% and 1%, and Na, Mn, Cu, Zn, and B were less than 0.1%. The Ca content in Xanthoparmelia camtschadalis was much higher than that in vascular plant. With an increasing grazing rate, the C concentration decreased, while N increased. The C/N ratio was the lowest under moderate and heavy grazing treatments. Ca, Mg, K, Fe, Mn and Cu contents were higher under grazing treatments. The changes of biomass and element composition of Xanthoparmelia camtschadalis had a good response to grazing rate, and hence, it was a good indicator to indicate the healthy condition and changes of biogeochemistry cycles in grassland ecosystems. PMID- 11758416 TI - [Energy production of plants in grass, Dicranopteris dichotoma and Rhodomyrtus tomentosa communities in Hong Kong]. AB - With harvest method and caloric value analysis, this paper studied the caloric values, standing energy, net fixed energy and net standing energy increment of three plant communities i.e., grass, Dicranopteris dichotoma and Rhodomyrtus tomentosa, in Hong Kong. The results showed that the caloric value was higher in D. dichotoma community and lower in grass community. The standing energy of plants in grass, D. dichotoma and R. tomentosa community was 18,638, 38,436 and 65,632 kJ.m-2; net fixed energy was 13,286, 20,354 and 18,784 kJ.m-2.yr-1; and net standing energy increment was 3437, 9626 and 6695 kJ.m-2.yr-1, respectively. Compared with southern subtropical evergreen broad-leaved forest, the standing energy, net fixed energy and net standing energy increment were lower in grass, D. dichotoma and R. tomentosa communities, which resulted from deforestation and other human disturbance. This indicated that vegetation conversion due to human disturbance would reduce the utilization coefficient of solar energy. Net fixed energy was also found to be reduced significantly with increasing intensity of human disturbance. PMID- 11758417 TI - [Comparative study on clonal and sexual reproductive traits of Leymus chinensis populations in different habitats]. AB - The variations of clonal and reproductive traits between four Leymus chinensis populations in different habitats were studied on northeast grasslands of China. The results showed that significant differences existed among Leymus chinensis populations in both clone traits (vegetative shoot densities and tiller densities) and sexual reproduction traits (reproductive shoot densities, reproductive shoot differentiation and reproductive effects), primarily due to the habitat heterogeneity of sites, especially the difference in soil moisture. The difference between grassland population and dune population was relatively greater, and the average vegetative shoot density, tiller density and sexual shoot density from grassland population were 50%, 30% and 200% greater than those from dune, respectively. PMID- 11758418 TI - [Caloric value and energy allocation of Chloris virgata in northeast grassland]. AB - The rules of seasonal changes in caloric values of individual plant, stem, and leaves of Chloris virgata were similar, which had two peak values from early July to early August, and then decreased gradually. Those of inflorescence assumed U shape, and had two peak values in early August and middle September, respectively. The seasonal changes in caloric values of dead standing were irregular, and the maximum value was appeared in early August. The seasonal changes in existent energy value of the aboveground parts in Chloris virgata population presented double peak curve. The two peak values were appeared in early August and early September respectively, and the maximum value was 7381.27 kJ.m-2 in early September. The energy allocation in different seasons was leaf > stem in early July, stem > leaf > dead standing in middle July, stem > leaf > inflorescence > dead standing in August, stem > inflorescence > leaf > dead standing in early September, and stem > inflorescence > dead standing > leaf in middle September. The vertical structure of energy in the aboveground parts was that the energy value gradually increased from the earth's surface to 20 cm high, and then decreased. The maximum value, which accounted for 25.75% of energy in the aboveground parts, was appeared in the layer of 10-20 cm high. In the underground parts, the energy value progressively decreased with the increase of depth, and the maximum value, which accounted for 74.21% of energy in the underground parts, was appeared in the layer of 0-10 cm depth. PMID- 11758419 TI - [Relationship between soil water content and water use efficiency of apple leaves]. AB - The relationship between soil water content and water use efficiency (WUE) of apple tree leaf was examined, and the mechanism of WUE variation was also studied by using pot-culture. The results showed that the WUE was upmost when soil water relative content (SWC) reached 52.0%. The increase of WUE when SWC decreased from 77.2% to 52.0% was mainly caused by the change of stomatal conductance. The decline of carboxylation efficiency resulted in the decrease of WUE when SWC decreased from 52.0% to 20.1%. The WUE returned up after being rewatered, but could not reach the control level within a week. The WUE decreased when the soil was waterlogged, but reached the control level in three days after being waterlogged. After the third day, the WUE decreased gradually with the extending of the time being waterlogged. On the sixth day being waterlogged, the carboxylation efficiency decreased. PMID- 11758420 TI - [Runoff loss ways of nutrients in non-irrigated farmland in Hefei outskirts]. AB - Taking non-irrigated flatlands in Hefei outskirts as experiment observation areas, yellow brown soil as selected soil type, and < 3 degrees as ground slope, the time of runoff development, runoff quantities, and silt carrying capacity under different rainfall intensity were observed on the non-irrigated farmlands with different kinds of crops such as grain, oil, cotton and vegetables, and with different coverage for continuous 3 years. Based on the observation, water and soil samples were collected and analyzed. The results showed that the loss way of the surface soil and nutrients in non-irrigated flatlands was obviously different from that on the sloping fields and on the upland. Over 98% of available N, P, and K nutrient loss were run off by chemical erosion. Physical erosion was the main way of the surface soil and organic matter loss, and 96.14% of total organic loss was caused by physical erosion. PMID- 11758421 TI - [Effect of rare earth elements on the seedling ratio of crops]. AB - The effects of rare earth elements(REEs) on the relative seedling ratio of three crops(rice, rape and soybean) in three soil(red soil, yellow fluvo-aquic soil and yellow cinnamon soil) were studied according to OECD method, and the LC50 were obtained. Toxicity effect of REEs on rice was minimum among the crops tested. The toxicity on crops in yellow cinnamon soil was lower, whereas on soybean in yellow fluvo-aquic soil and on rape in red earth were higher. PMID- 11758422 TI - [Water distribution and microclimatic effects of sprinkler irrigation on spring wheat field]. AB - Measurements of sprinkler irrigation on spring wheat field indicated that spring wheat canopy could intercept water by 25-30%, and compared with that above canopy in first milking period, the uniformity coefficient below canopy could be increased by 7-9%. Floating and evaporation loss of sprinkler irrigation water could reach 20-25% of the total. In addition, sprinkler irrigation on spring wheat field could decrease air and soil temperature, and increase air actual vapor pressure and relative humidity, which played a definite role in restraining crop transpiration. PMID- 11758423 TI - [Effect of rice canopy structural changes on bidirectional reflectance]. AB - The study of vegetation bidirectional reflectance is useful for remote sensing data interpretation. Vegetation canopies information such as leaf area index, mean leaf inclination, mean plant height, and coverage, can be inverted from vegetation bidirectional reflectance. This paper discussed the dynamics of vegetation canopies reflectance with vegetation canopy structures by measuring rice canopy structure and bidirectional reflectance at 26, 35, 41, 49, 62, 67 and 86 days after transplanting. It is concluded that the sensitivity of vegetation canopies to directional reflectance variations varied with canopy structures, and hence, through bidirectional reflectance, more information about canopy structure can be know. PMID- 11758424 TI - [Symbiotic effect of cultivating fish in rice field in north China]. AB - Experiment on rice-fish symbiosis in north China showed that the rice production in rice-fish field was a bit higher than control, and the output-input ratio of energy, utilization efficiency of solar energy and soil organic matter content increased 0.08, 0.1 and 0.24%, respectively. The banded sclerotic blight incidence decreased 3.8% and the net economic income increased 900 RMB yuan per hectare. All the resul;ts showed that rice-fish symbiotic system had a good symbiotic effect. PMID- 11758426 TI - [Relationship between production input and secondary succession of earthworm population in salinity transforming region of north China--a case study in Quzhou County]. AB - The analysis on earthworm diversity in the farmland ecosystem of salinity transforming region in Quzhou County, Hebei Province, showed that the secondary succession of earthworm population had a close relationship with the input of fertilizer and manure. An optimum input, especially manure input, could accelerate the secondary succession. The general trend of earthworm distribution was in the order of second experimental district > first experimental district > third experimental district > original area. The distribution, biomass and amount of earthworm varied in different types of land-use, and the relationship was in the order of vegetable field > crop field > orchard and margin land. PMID- 11758425 TI - [Stress response of Nilaparvata lugens at high temperature and activities of its protective enzyme systems]. AB - The nymphae and different wing-form adults of Brown Planthopper (BPH) were treated intermittently at 34 degrees C, 36 degrees C and 38 degrees C. During the process of heat shock treatment, the variation of the activities of the endogenous enzymes of protective system and the content of lipid peroxides (LPO) in BPH were researched. The results showed that the effect of heat shock treatments on CAT activity in 4th instar of nymphae was higher than that in 3rd and 5th instar. The CAT activity in BPH adults increased with the day-age, and 36 degrees C was the suitable temperature at which H2O2 was scavenged by CAT. The GSH-px activity was higher in old than that in young nymphae, and the ability of GSH-px to scavenge H2O2 was higher in old adults than in those adults emerged early. The activity of SOD had a positive correlation with the treated temperatures, and decreased with the increase of nymphae instar and the day-age of adults after emergence at the same temperature. The activities of CAT, GSH-px, and SOD in macropterous adults were higher than those in brachypterous adults. There were no significant difference for the activities of CAT, GSH-px and SOD between female and male adults (alpha > 0.05). The content of LPO in BPH increased with the rise of treated temperature, and also increased with the increase of instars in nymphae and day-age after emergence in adults at the same temperature. The LPO content was higher in brachypterous than in macropterous adults. PMID- 11758427 TI - [Effect of environmental factors on N and P uptake by Gracilaria tenuistipitata var. liui Zhang et Xia]. AB - The effect of light intensity, pH, temperature, salinity on the uptake of nitrogen and phosphorus by Gracilaria tenuistipitata var. liui Zhang et Xia was were studied under laboratory conditions. The uptake rate of nitrogen reached as high as 0.32-0.36 mumol.g-1.h-1 at favorable light intensity of 800-2400 mumol photon.m-2.s-1, while that of phosphorus reached 0.017-0.018 mumol.g-1.h-1 at 320 1600 mumol photon.m-2.s-1. The nutrient uptake rate reached the maximum at pH 8.0. A significant difference of N uptake rate at different temperatures or salinities and that of P uptake rate at different temperatures were found. The N uptake rate was higher at 21-26 degrees C and 20@1000-28@1000, but P uptake was higher at 21-26 degrees C. There was no interaction between temperature and salinity. PMID- 11758429 TI - [Tree stomatal infiltration and SO2 injury and protection effect of ABA]. AB - This paper deals with relation between tree stomatal infiltration and SO2 injury and the protection effect of ABA. Experiments of SO2 smoking to the selected trees were carried out and the data were collected in the field. The results show that stomatal infiltration was a comparably constant index for certain tree species. The infiltration of trees is negatively correlated with the combine extent of chlorophy, but not obviously. The index is also positively correlated with K+ efflux in leaf(r = 0.92, alpha < 0.01). In the experiment of SO2 smoking, the effect on infiltration of same species under different SO2 concentration was little, less than one grade, while K+ efflux increased with the increment of SO2 amount absorbed by the leaves. When the leaves were sprayed with ABA solution, the higher the ABA solution concentration was, the lower the K+ efflux was. When leaves sprayed with ABA solution were smoked with 2.5 mol.L-1 for four hours, the infiltration of leaves with 30 mol.L-1 ABA solution dropped 1.5-3 and K+ concentration decreased 36.5%-54.8% on leaves. It indicates that the ABA solution on leaves has remarkable effect of protection of SO2 injury. PMID- 11758428 TI - [Effect of benzo(a)pyrene on antioxidant enzyme activities in Boleophthalmus pectinirostris liver]. AB - The effect of different BaP concentrations on the activities of superoxide dismutase(SOD), glutathione peroxidase (GPx) and catalase(CAT) in Boleophthalmus pectinirostris liver was studied under experimental condition. The results showed that the activities of antioxidant enzymes did not change too much with BaP exposure in lower concentration, whereas the SOD and GPx activities were increased significantly with BaP exposure in higher concentration. No statistical changes were observed in the effect of BaP exposure in different concentrations on CAT activities throughout the experiment. PMID- 11758430 TI - [Influence of elevated atmospheric CO2 concentration on photosynthesis and leaf nitrogen partition in process of photosynthetic carbon cycle in Musa paradisiaca]. AB - The photosynthetic rate (Pn) in leaves of Musa paradisiaca grown under elevated CO2 concentration (700 +/- 56 microliters.L-1) for one week was 5.14 +/- 0.32 mumol.m-2.s-1, 22.1% higher than that under ambient CO2 concentration, while under elevated CO2 concentration for 8 week, the Pn decreased by 18.1%. It can be inferred that the photosynthetic acclimation to elevated CO2 concentration and the Pn inhibition occurred in leaves of M. paradisiaca. The respiration rate in light (Rd) was lower in leaves under higher CO2 concentration, compared with that under ambient CO2 concentration. If the respiration in light was not included, the difference in CO2 compensation point for the leaves of both plants was not significant. Under higher CO2 concentration for 8 weeks, the maximum carboxylation rate(Vcmax) and electron transportation rate (J) in leaves decreased respectively by 30.5% and 14.8%, compared with that under ambient CO2 concentration. The calculated apparent quantum yield (alpha) in leaves under elevated CO2 concentration according to the initial slope of Pn/PAR was reduced to 0.014 +/- 0.010 molCO2.mol-1 quanta, compared with the value of 0.025 +/- 0.005 molCO2.mol-1 quanta in the control. The efficiency of light energy conversion also decreased from 0.203 to 0.136 electrons.quanta-1 in plants under elevated CO2 concentration. A lower partitioning coefficient for leaf nitrogen in Rubisco, bioenergetics and thylakoid light-harvesting components was observed in plants under higher CO2 concentration. The results indicated that the multi process of photosynthesis was suppressed significantly by a long-term (8 weeks) higher CO2 concentration incubation. PMID- 11758431 TI - [Chelate-induced phytoextraction of copper contaminated upland red soil]. AB - A copper spiked red soil was used in pot experiment to study the effects of EDTA and low molecule weight organic acids on Cu speciation in soil, and Cu uptake by Brassica juncea. The results showed that the mobility of Cu in soil was improved obviously when EDTA was added at the vigorous growth stage. Both water extractable and exchangeable Cu concentration increased significantly following EDTA addition. Citric acid and malic acid only had an effect on water-extractable Cu, and no effect on Cu uptake by the plant. EDTA significantly increased the concentration of Cu in plant leaves and roots, and the Cu uptake by Brassica juncea. All of these indicated the chelate-induced phytoextraction. PMID- 11758432 TI - [Preliminary study on anaerobic bioremediation process for pentachlorophenol (PCP)-contaminated soil]. AB - The performances of soil-slurry process with supplement of anaerobic granular sludge for remediating PCP-contaminated soil was investigated. The results showed that inherent anaerobic microbes in soil exhibited a little dechlorinating activity for simulative contaminated soil with 30 mg.kg-1 of PCP, the average PCP degradation rates within 28 d was 0.258 mg.kg-1.d-1. In soil slurry processes with 5 g.kg-1 granular sludge at aerobic, aerobic/anaerobic and anaerobic operation, the average PCP degradation rates within 28 d were 0.269, 0.291/0.842 and 0.892 mg.kg-1.d-1, respectively. PCP degradation rates were increased with increasing the amounts of anaerobic granular sludge, 0.834, 0.843, 0.928 mg.kg 1.d-1 of the average PCP degradation rates within 35 d were achieved in soil slurry processes supplemented with 5, 10, 25 g.kg-1 of granular sludge, respectively. This bioremediation process also presented higher initial PCP degradation rate for higher concentration(60 mg.kg-1) of PCP in soil. PMID- 11758433 TI - [Photobacterium phosphoreum assay on the toxicity of soil contaminated by heavy metals]. AB - The toxicity of soil artificially contaminated by heavy metals was assessed with Photobacterium phosphoreum. The results showed that the duration of optimum balance was 24 hours, and that of optimum extraction was 2 hours. Two leaching methods were compared, and data showed that optimum leaching solvent was hydrocarbon chloride with a concentration of 0.1 mol.L-1 HCL. Dose-response curve indicated that the content of heavy metals was positively related with the toxicity of soil. The general detection limit given by EC50 of soil contaminated by single heavy metal were Cd 26.12 mg.kg-1, Cu 291.48 mg.kg-1, Zn 72.46 mg.kg-1 and Pb 2174.93 mg.kg-1. This study also indicated the toxicity of complex heavy metals pollution in soil was stronger than that of individual element. The research could provide a theoretic base for the remediation of soil contaminated by heavy metals. PMID- 11758434 TI - [Co-metabolic degradation of pyrene in soil]. AB - High molecular weight Polycyclic Aromatic Hydrocarbons (PAHs) are always degraded by means of co-metabolism. This study compared the degradation process of pyrene as sole source of carbon and energy and co-metabolic degradation process of pyrene. The degradation rate of pyrene after 25 days in the first process was 57%, while the degradation rate of pyrene in the co-metabolic processes were about 80%. The half-life of pyrene in the co-metabolic process was shorter than those in the processes without co-metabolism. Salicylic acid, phthalic acid, sodium succinate could serve as co-metabolic substrate to enhance the degradation rate of pyrene, and sodium succinate has the best effect. There was co-metabolic relationship between pyrene and phenanthrene which was a kind of low molecular weight PAHs, phenanthrene accelerated the degradation of pyrene, while naphthalene didn't. The principle of the co-metabolism and the optimal material used as co-metabolic substrate were demonstrated in this paper. PMID- 11758435 TI - [Transportation and transformation of 14C-phenanthrene in closed chamber (nutrient solution-lava-plant-air) system]. AB - The transportation and transformation of 14C-phenanthrene in a closed 'plant-lava nutrient solution-air' chamber system was studied by using radioactivity technology. The results showed that in this closed chamber system, phenanthrene was degraded fast. The radioactivity of 14C left at 23d in the nutrient solution was only 25% of applied. At the end of experiment (46d), the distribution sequence of 14C activity in the components of closed chamber system was root (38.55%) > volatile organic compounds (VOCs, 17.68%) > lava (14.35%) > CO2 (11.42%) > stem (2%). 14C-activities in plant tissue were combined with the tissue, and existed in the forms of lava-bound(root 4.68%; stem and leaves 0.68%) and polar metabolites (root 23.14%; stem 0.78%). PMID- 11758436 TI - [Physiology and development of two Roegneria kamoji populations stressed by copper]. AB - Roegneria kamoji grown copper tailings had weak stem, short height, and thick leave color, while its counterpart on normal soil was the opposite. Exposed to copper, R. kamoji had a decreased chlorophyll content. A certain concentration of copper could promote the seed germination of R. kamoji, and the extract of copper tailings did not decrease the seed germination rate, but deferred the germination. Root growth test indicated that when the concentration of copper was 0.125 mg.L-1, the rooting of R. kamoji was promoted. If the concentration was more than 0.25 mg.L-1, the rooting was inhibited significantly. R. kamoji colonized on normal soil wase more sensitive to copper than that on Cu-polluted soil. PMID- 11758437 TI - [Identification of key toxicants in a bleaching effluent--a case study]. AB - The toxicity identification evaluation (TIE) was conducted with a toxic bleaching effluent to identify its toxic components. Toxicity characterisation procedures (phase I) indicated that the primary toxicants in the effluent were volatile, and could be reduced by sodium thiosulfate. Toxicity-based fractionation techniques (phase II) were conducted, and the oxidation organic chloridates were found not to be the major toxicants. Deletion approach of phase III confirmed that the toxicity decreased with the decrease of free and total residual chlorine concentrations, indicating that Cl2, HClO and ClO- were identified as primary toxicants in the effluent. PMID- 11758438 TI - [Chemical defense of plant to mammalian herbivore]. AB - The research progress in the chemical defense of plant to mammalian herbivore was reviewed in this paper. The plant secondary compounds mainly are phenolics, terpenoids and nitrogen-containing compounds. The defense efficiency of plant to mammalian herbivores is different with the types and content of secondary compounds in plant. Secondary compounds inhibited the foraging of mammalian herbivores by affecting the intake, digestion, metabolites and reproduction of animal. It is the main trends to study the mode of coevolution of plant and animals mediated by plant secondary compounds. PMID- 11758439 TI - [Soil macropore and its studying methodology]. AB - This paper discusses the definition, size, types, formation of soil macropores. Soil macropore (> 0.03 mm) is the pore space that provides preferential paths of flow. The shape of macropore varies from crack or fissure, through to cylindrical pipe. Macropore is formed in main ways: by plant roots and soil fauna; wet-dry and freeze-thaw cycles; chemical weathering. The studying method of macropore divided into direct measurement and indirect description, which suitability and limitation are also reviewed. PMID- 11758440 TI - [New advances in research of combined pollution]. AB - Combined pollution has become one of the important directions of environmental science at present. In this paper, new advances of studies on combined pollution were summarized. The studies of inorganic combined pollution, inorganic-organic combined pollution and organic combined pollution were reviewed. The mechanisms of combined pollution were approached from chemistry, physiology, enzymology, cytology and molecular biology. Then some problems and developing aspects on the research of combined pollution were put forward. PMID- 11758441 TI - [Analysis on landscape ecology literatures in China during recent ten years]. AB - Landscape ecology has achieved great progress since its introduction to China in early 1980s. Based on 619 collections of literatures and 14 collections of books, this paper has all the literatures and books classified, arranged in order and counted on different special subject. According to the results of classified statistics, the authors discuss and analyze how landscape ecology research was going in China during 1990s. Moreover, this paper can also provide scientific basis for those who want to grasp and keep abreast of current focus and trend of landscape ecology in China. PMID- 11758442 TI - [Effect of boron fertilization on B uptake and utilization by oilseed rape(Brassica napus L.) under different soil moisture regimes]. AB - Pot experiment was conducted in greenhouse to determine the effect of boron fertilization on B uptake and utilization by oilseed rape at seedling stage as influenced by soil moisture regime. The results showed that B concentration in shoot and root increased with the increase of soil water content and B fertilization level, while its utilization efficiency(BUE) and mobilization index(BMI) increased with the decrease of soil water content and B application level. Differences in BUE and BMI of test oilseed rape cultivars were significant, i.e., V1 showed higher BUE and BMI than V4 under the same conditions. It is concluded that BUE and B mobility in plant were the major factors responsible for the differences in response of different oilseed rape cultivars to B deficiency. PMID- 11758443 TI - Crystal structures of calcium orthophosphates. PMID- 11758444 TI - Interfacial properties of hydroxyapatite, fluoroapatite and octacalcium phosphate. PMID- 11758445 TI - Amorphous calcium phosphate. AB - ACP is a unique calcium phosphate in that it lacks long-range crystalline order. Yet the constancy in the composition of ACP over a wide range of solution conditions suggests a well-defined local structural unit. Although this order within disorder is the most distinguishing feature of ACP, the solution instability of ACP and its ready transformation into crystalline phases such as OCP and apatite may be of greater biological relevance. In particular, the initiating role ACP plays in matrix vesicle mineralization raises the importance of this phase from a mere laboratory curiosity to that of a key intermediate in skeletal calcification. PMID- 11758447 TI - Formation of octacalcium phosphate in vitro. PMID- 11758446 TI - Calcium phosphate cements. PMID- 11758448 TI - Role of OCP in biological processes. PMID- 11758449 TI - Octacalcium phosphate carboxylates. PMID- 11758450 TI - Solubility of calcium phosphates. PMID- 11758451 TI - Transcription initiation: imposing specificity by localization. AB - Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acetylaters, etc.--have multiple potential substrates. Regulation entails substrate selection, a process effected by a mechanism we call regulated localization. This formulation is particularly well illustrated by the mechanisms of gene regulation. Analysis of these mechanisms reveals that regulated localization requires simple molecular interactions. These molecular interactions readily lend themselves to combinatorial control. This system of regulation is highly 'evolvable'. Its use accounts, at least in part, for the nature of many of the complexities observed in biological systems. PMID- 11758452 TI - To live or die--a cell's choice. AB - Cell death is one of several choices a cell faces in response to injury. The cell's inherent properties and its external environment determine which pathway is chosen. Interaction between transcription factors such as p53, E2F and c-Myc acts to finely tune the pathway selection process. Once the cell death pathway is initiated cell, survival proteins can stop it at different stages upstream of the activation of effector caspases. The exact point of no return along the cell death pathway is unknown, but is likely to vary between cells. It is unlikely to be a single step, but rather a short process leading to irreversibility of the pathway. PMID- 11758453 TI - Future perspectives. AB - Transcription is coupled to splicing and other post-transcriptional processes. The importance of transcription factors in developmental biology and disease is underlined by genetic analysis in flies and humans. The genome project is identifying large numbers of novel transcription factors and RNA-binding proteins. Proteins may have multiple functions, acting at the transcriptional and post-transcriptional levels. The vast amount of novel biological information requires new, high-throughput approaches and bioinformatics. PMID- 11758454 TI - Activation and repression of transcription initiation in bacteria. AB - Transcription initiation is the principal step at which bacterial gene expression is regulated. Bacterial transcription is due to a single multisubunit RNA polymerase. The potential transcription initiation rate of any promoter is set by the efficiency with which RNA polymerase recognizes the different promoter sequence elements. The sigma subunit plays the major role in the process of promoter recognition. Different RNA polymerase sigma subunits can guide RNA polymerase to different promoters. The E. coli genome encodes seven different sigma subunits, each of which allows the cell to respond to different environmental stimuli. A large number of transcription factors up-regulate and down-regulate expression from different promoters in response to environmental signals. Many transcription activators function by making a direct interaction with RNA polymerase. Some activators function by altering the conformation of promoter DNA. Most transcription repressors function by blocking access of RNA polymerase to their target promoter. In some cases, optimal repression depends on multiply bound repressor molecules that interact in complex ways. Many promoters are regulated by more than one transcription factor. A variety of mechanisms whereby a promoter can be regulated by a repressor and an activator, or by two activators, is known. PMID- 11758455 TI - Regulation of the initiation of eukaryotic transcription. AB - DNA sequences that determine transcriptional regulation of a typical eukaryotic gene consist of a core promoter, which serves as a binding site for the GTF TFIID, and regulatory promoter or enhancer sequences, which bind transcriptional activators. The RNA polymerase II transcription machinery consists of over 50 proteins which are thought to bind to the core promoter in as few as two steps: binding of TFIIA-TFIID, followed by binding of a large pre-assembled holoenzyme complex consisting of the remaining GTFs, RNA polymerase II and associated regulatory proteins. Activators function to increase binding of the transcription machinery to the promoter in at least two ways: (i) simple protein-protein interactions with activators increases the affinity of the transcription machinery for the promoter, and (ii) some activators stabilize a conformation of the TFIIA-TFIID-DNA complex that enhances binding of the holoenzyme. Recent studies have identified many co-activators that function with activators to increase transcription by the RNA polymerase II transcription machinery. Although some co-activators may serve as bridges to connect activators with the transcription machinery, the mechanism of action of many co-activators has not yet been determined. PMID- 11758456 TI - Transcriptional regulation in the context of chromatin structure. AB - A wide variety of histone-like proteins can be assembled into nucleosomal structures. Core and linker histone variants, proteins of the histone-fold and winged-helix families can all contribute to the local differentiation of functional chromosomal domains. It is very difficult to disrupt core histone interactions within a nucleosome in vivo. Histones H3 and H4 do not exchange out of chromatin outside S-phase. Histones H2A and H2B do exchange out of chromatin, but do so predominantly during transcription. This confers stability on the nucleosome during the cell cycle. Linker histones have a much less stable association with nucleosomal DNA, allowing for reversible activation of transcription. A distinct feature of histone interactions with nucleosomal DNA is the exposure of DNA on the surface of the nucleosome. One side of DNA is occluded on the histone surface, but the other is exposed and potentially accessible to other regulatory proteins. A major contributory factor to the functional specialization of chromatin is the capacity to target nucleosome modification and disruption. PMID- 11758457 TI - DNA methylation and control of gene expression in vertebrate development. AB - MeCpGs act as ligands for nuclear factors (repressors) that are components of chromatin modification and remodelling activities. The DNA-methylation-mediated repression system (Dnmt1s, MeCPs and MBDs) is highly conserved in vertebrates. DNA methylation is essential for normal vertebrate development. It is possible (but remains unproven) that the role of DNA methylation in regulating development is highly conserved in vertebrates. In mammals, DNA methylation has an additional role in regulating the expression of imprinted genes and in controlling X inactivation. PMID- 11758458 TI - Signalling from the cell surface to the nucleus. AB - Transcriptional initiation is regulated by altering the properties of promoter specific DNA-binding proteins, such that these proteins either show altered interaction with the basal transcriptional machinery, or show changes in their cytoplasmic/nuclear distribution. Information is passed from the receptor to the transcription factor by a process of post-translational modifications of pathway components. Post-translational modifications can include phosphorylations or dephosphorylations, which are reversible, and proteolysis, which is irreversible. Specificity within a linear signal transduction pathway is preserved by the existence of scaffold proteins, which serve to co-localize many of the factors from a given linear pathway. PMID- 11758459 TI - Control of gene expression and the cell cycle. AB - The pRb tumour suppressor protein is an essential component of the cell-cycle clock, integrating both positive and negative signals for cellular growth and proliferation with the transcription machinery. pRb exerts its tumour suppression function by both antagonizing and synergizing with downstream effectors, such as E2F. pRb has two modes of action, it can inactivate E2F transcription activity or it can assemble an active repression complex with E2F. Apart from E2F, pRb interacts with various factors to promote cellular differentiation. The differentiation properties of pRb are likely to contribute partly to its tumour suppressor function. It is also clear that pRb is a master regulator for transcription. It can both activate and repress transcription in a context dependent manner. pRb interacts directly with histone acetyltransferase, histone deacetylases and SWI/SNF proteins, all of which are classes of proteins involved in chromatin remodelling. Last, but not least, pRb regulates transcription driven by all three polymerases, thereby integrating the cell-cycle clock with the biosynthetic capacity of the cell in controlling cellular proliferation and growth. PMID- 11758460 TI - Regulation of mRNA translation. AB - The control of mRNA translation plays an important role in regulating gene expression in diverse situations. Nutrients, especially amino acids, regulate translation to control the expression of specific proteins including transcriptional activators and ribosomal proteins. Sequence elements in the 5'- or 3'-untranslated regions of mRNAs can control their translation. Hormones such as insulin activate protein synthesis by switching on translation factors required for overall mRNA translation. Viruses employ a range of stratagems to ensure efficient translation of their mRNAs and in some cases to inhibit host cell translation. During development, control of mRNA translation regulates gene expression both spatially and temporally. PMID- 11758461 TI - [Age-related features of neuromuscular function in rats with hyperthyroidism]. AB - Studied features of functioning of nervous-muscular system at white rats of two age groups: preadolescent (5 weeks) and puberal (24 weeks), in conditions experimental hyperthyroidism (HT). It is established, that in conditions HT at action of the raised concentration thyroxine characteristics of excitation gastrocnemius muscles essentially changed at irritation of a sciatic nerve in groups preadolescent and puberal animals. In all age groups in conditions HT increase of a threshold of excitation gastrocnemius muscles is marked at indirect stimulation and decrease at direct stimulation; also in all age groups in conditions HT reduction of time chronaxy muscles is fixed, both at direct, and at indirect irritation. At preadolescent animals, as against puberal in conditions HT at action of the raised concentration thyroxine on nervous-muscular system it is not revealed authentic change of the latent period and amplitude of potential of action (PA). The conclusion is made, that in conditions HT change of a threshold of excitation and chronaxy gastrocnemius muscles both at direct, and at indirect irritation do not carry age specificity and have an identical orientation, both at preadolescent, and at puberal rats. At preadolescent animals in conditions HT, as against puberal the parameter of amplitude and latent period PA authentically did not change, that can testify to smaller sensitivity of the caused answers gastrocnemius muscles to the raised concentration thyroxine, probably, by virtue of immaturity peripheral neuromotor the device. PMID- 11758462 TI - [Changes in intracellular mechanisms in sensory neurons in experimental diabetes mellitus]. AB - Here we summarises the results of experimental investigation of changes in intracellular calcium homeostasis in sensory neurones of rats with streptozotocin induced diabetes mellitus. Decrease in the calcium-accumulating function of both inositol-trisphosphate- as well as caffeine-sensitive endoplasmic reticulum has been detected both in primary sensory neurones of dorsal root ganglia and in secondary neurones of the spinal cord dorsal horn. Predominant depression in the functioning of metabotropic receptors of ligand-gated channels compared with those of ionotropic ones has been demonstrated. Changes in the pharmacological sensitivity of potential-operated calcium channels (predominantly of L-type), linked, probably, with alterations of functional connections between membrane channels and endoplasmic reticulum, are described. A predominant role of changes in the functioning of intracellular Ca(2+)-accumulating structures, leading to prolongation of depolarisation-induced Ca2+ transients in primary and secondary sensory neurones and corresponding changes in the transmission of nociceptive signals during diabetic neuropathy are discussed. PMID- 11758463 TI - [Effect of potassium channel openers on lysosomal function and morphology during acute hypoxic hypoxia]. AB - It was studying the effect of fluorinecontain pinacidil analogs (PF-5 and PF-10), which are the K(+)-channel openers, on morphofunctional lysosomes state at lung and heart tissues. The investigation was made on white pubertal rat-males under acute (30 min) hypoxic hypoxia (7% O2 [symbol: see text] N2). The application of PF-5 and PF-10 under acute hypoxic hypoxia leads in lung and myocardium tissues to morphofunctional changes of lysosome system in investigated cells, which were connected with decreasing of enzyemia. It, partly, may be explain by increasing of connected enzyme forms synthesis, because such forms are the functional latent, so the output of enzymes in blood under unfavourable conditions increased. PMID- 11758465 TI - [Interactions of human psycho-somato-visceral functions]. AB - Three typological groups (clusters) of human were picked out by complex of psycho somato-visceral indexes. The most informaton and suitable for estimation indexes for dividing population of human into typological groups were established. Each group of persons is characterised by combination of properties that differ statistically from other groups. Some of this properties are genetic dependent. PMID- 11758464 TI - [Inhibitors of arginase in the L-arginine metabolic pathway as a new class of antihypertensive drugs: effect of carbamide on lipid oxidative metabolism and on vessel tonus during arterial hypertension]. AB - Have studied action of chronic urea--an arginase inhibitor--introduction (40 mg/kg, 28 days) on blood pressure, endothelium-dependent reactions of aorta smooth muscle cells (SMC) and nonenzymatic (contents of diene conjugates and H2O2) and enzymatic (contents of free arachidonic acid and vasoconstrictic eicosanoids LTC4 and TXA2) oxidizing lipid metabolism of heart, aorta, plasma and erythrocytes of spontaneously hypertensive rats. Have shown, that urea down regulate blood pressure without any normalization of endothelium-dependent reactions of SMC of aorta and down regulate both enzymatic and nonenzymatic oxidizing lipid metabolism. Down regulation of two alternative (by cyclooxygenase and by lipoxygenase) enzymatic pathways of free arachidonic acid oxidizing metabolism by urea can be one of mechanisms of its antihypertensive action. The possibility of urea use at hypertension and various pathophysiological conditions are discussed. PMID- 11758466 TI - [Modeling of experimental allergic encephalomyelitis in rats and immunomodulation with allogeneic brain cells]. AB - We studied the immunocorrective effect of the allogenic new-born brain cells on the model of rats experimental allergic encephalomyelitis (EAE). EAE was induced by the immunization of old rats spinal cord homogenate in Freund's adjuvant. Correction was carried on the 12-th, 14-th, 16-th day after the induction of the EAE by the intraperitoneum injection of rat's new-born brain fractions enriched with neurons and glial cells. A positive clinical effect was achieved by the employment of neurons (the stabilization of encephalomyelitis and the acceleration of the recovery). The glia correction was accompanied by the aggravation in the course of encephalomielitis and by extension of its clinical manifestation period. The obtained results testify to the existence of both an immunoregulative and a neurotrophic influence of the neuron fraction of the new born brain cells. The mechanism of a corrective effect needs further special investigation. PMID- 11758467 TI - [Mechanism of nitric oxide's effect on the sensitivity of smooth muscle contractions to calcium]. AB - It was investigated whether the SH-groups of contractile proteins are involved in NO-induced relaxation of saponin-skinned smooth muscle strips. Both, the thiol specific alkylating agent N-ethylmaleamide (NEM), and thiol-reducing agent dithiotreitol (DTT) induced relaxation of maximally activated skinned rat portal vein preparations. The relaxing effects of DTT and nitric oxide donor sodium nitroprusside were not additive. After the relaxation, induced by one of this agent, the effect of the other one was negligible. We suggest that NO-induced smooth muscle relaxation be due to decreasing of force sensitivity to Ca2+. This effect of nitric oxide is realized by its interaction with critical thiol groups of smooth muscle contractile proteins. PMID- 11758468 TI - [Specific binding of GABA in the adrenal glands and catecholamine blood and adrenal gland levels in rats under stress with inhibited functioning of the hypothalamus-hypophyseal-adrenocortical systems]. AB - Forced swimming of intact rats was accompanied by an activation of the hormonal link in sympatho-adrenal system and by a decrease in the level of specific binding of 14C-GABA by adrenal plasma membranes; the former was prevented with the administration of GABAergic preparations (baclofen, GABA-taurine) before stress. Under inhibition of the function of hypothalamo-pituitary-adrenocortical axis following multiple hydrocortisone administration and, in presence of developing metabolic disorders and adrenal secretion of catecholamines, the latter reacted to stress by a decrease in adrenalin, noradrenaline and dopamine secretion without changing the intensity of specific binding of GABA. Administration of GABAergic preparations before stress prevented the development of stress disorders of noradrenaline and dopamine secretion partially or completely, and sodium thiosulphate administration increased acutely specific binding of GABA with adrenal plasma membranes simultaneously preventing the accumulation of adrenal noradrenaline and the decrease in blood DOPA level. PMID- 11758469 TI - [Age-related changes in circadian and circannual fluctuations of the immune response and the number of cells in lymphoid organs of animals: a possible connection to thymic factors]. AB - The 24-hour and seasonal fluctuations of cellularity of thymus and spleen and antibody levels in male CBA/Ca mice and Wistar rats of different ages were investigated. In adult rats (6-11 mo) the peaks of thymus and spleen cellularity were at nights and in the daytime, respectively. In young mice (3 mo) the thymus and spleen cellularity were highest in autumn and spring, respectively. The titer (log2) of hemolysines in autumn was 16 times greater than in spring. Correlations between the rhythmical changes of cellularity of thymus and spleen and between the latter and the factor thymic serique (FTS) titer were found. With age (4 month and onward in mice and 17 months in rats), the peaks of amounts of cells in thymus and of its mass in night and in autumn and of the antibodies titers in autumn were diminished. The displacement of the acrophases of indicers to other seasons was seen. In old animals the rhythm of indices became monotonous. In aging the intrasystemic relations underwent changes (new relation appeared, while the existing ones weakened or disappeared). The chronic (18 mo) administration of thymus preparation thymalin increased FTS titer and promoted the appearance of the peak of antibodies in autumn. PMID- 11758470 TI - [The effects of ozone and toxic air particles on airway function in mice]. AB - We tested the hypothesis that exposures to particulate matter and ozone can produce asthma-like symptoms. Balb/c mice received a single intratracheal instillation of particulate matter and TiO2 or they were exposed to low concentration of ozone. We have established that exposure to particulate matter produces increased responsiveness to methacholine in mice. Exposure to ozone and TiO2 did not produce changes in respiratory mechanics. These data are spreading our understanding about mechanisms of environmental influence on airways. PMID- 11758471 TI - [Interleukin-2 and interleukin-4 blood levels in sinusitis]. AB - In acute inflammation the content of cytokines (IL-2, IL-4) is increase. Especially considerable is increase the content of anti-inflammation interleukins (IL-2, IL-4) in the blood. There are different displacements in chronical inflammation: the content of IL-2 and is increase, the content IL-4 is decrease. The question about a pathogenic role of established facts is discussing. In result of treatment the content of anti-inflammation interleukins in the blood of ill people has increase, and the content of anti-inflammation cytokine was decrease. The disbalance of anti-inflammation cytokines is reflect the acuteness a from of treatment and disposition of treatment and disposition of interleukin regulation of inflammation. PMID- 11758472 TI - [The effect of a nonprotein spleen factor on the course of delayed-type hypersensitivity and graft versus host reactions]. AB - The effects of splenoside on the reactions of delayed-type hypersensitivity and graft versus host were investigated. Even single splenoside injection (50 mg/10 g b.w.) increased graft versus host reaction in newborn mice-hybrids F1. Splenoside influences the delayed-type hypersensitivity reaction in dose-depending manner: the dose of 50 mg/10 g increases the reaction and 100 mg/10 g decreases it. PMID- 11758474 TI - [Effect of 12-hour work shifts of dispatchers of electric networks on their cardiovascular systems]. AB - Blood pressure, heart rate and haemodynamics parameters in dispatchers of electric networks were studied in productive conditions under two days rotation of 12-hour shifts (17 subjects, 1224 subject-observations). It was revealed, that taking and giving periods of the shifts activate cardiovascular system work to the pronounced extent (significant increase of blood pressure at the beginning and in the end of the shifts and heart rate--at the beginning of the shifts). That is accompanied with unfavourable changes of bloodcirculation selfregulation (BCS): Predominantly heart BCS that is forming at the beginning of the shifts, especially in the evening, gradually convert towards the mainly vascular one, that is especially pronounced after 8 hours of continuous working in the day shifts. Significant predominance of the vascular BCS is noted during second consecutive day shifts, predominance of the heart BCS is noted during second consecutive night shifts. This evidences the difficulty of the second consecutive 12-hour shifts to be maintained from the cardiovascular system. Breaking of BCS, that is repeated systematically, can promote forming of the steady unfavourable changes of dispatchers' cardiovascular system state. PMID- 11758473 TI - [Effect of hypergravity on the oxidative-antioxidative status of rats]. AB - The adaptogenic and antioxidant properties of new Ukrainian plant drug "Poliphytolum" was investigated on the model of stress, which was caused of hypergravitation 2 and 5 N.m2/kg2 action. It was established that hypergravitation makes typical stressory disturbances in oxidative homeostasis. The normalization action of "Polyphytolum" on lipid peroxidation is more strong in liver, spleen and blood, and less more--in brain. It may be caused of low level the drug in the brain tissue. PMID- 11758475 TI - [Physical development and formation of psychophysiological functions in young school-age children]. AB - The aim of investigation was to study of physical development and psychophysiological functions forming in children of young school age. Were studied 25 schoolchildren (12 girls and 13 boys) in 4 class of average school. Anthropometric and functional parameters as level of physical development were studied. In dynamics of school year were studied of psychic functions. The investigations are showed that process of learning provokes of fatigue and reflects on psychic functions efficiency as well as negative influence on physical development. The psychic functions forming characterized to gradual mobilization of new elements of functional system during school year in children of young school age. PMID- 11758476 TI - [The effects of free radical oxidation on skin surfaces with disturbed microcirculation]. AB - Quantity of primary and secondary products of peroxide oxidation of lipides in the case of broken microcirculation was investigated in biophates of skin. It was found that broken microcirculation led to the surplus accumulation of products of lipide peroxide oxidation. Prooxydanto-oxydantic homeostasis disturbance has very strong influence on premature skin atrophy. PMID- 11758477 TI - [Role of individual-typological characteristics of higher nervous activity for professional personnel selection]. AB - The role of properties of the basic nervous processes in successes of study, development and use of the acquired skills in the appropriate kinds of labour activity and in particular in that of them was shown, the specificity of which activity requires of the man of high emotional stability, the responsibility for final result of the accepted decisions and is carried out in some cases in conditions of high speeds, high rates of activity, excessiveness or deficiency of receipt of the information. The conclusion was made that individual-tepological properties of higher nervous activity, as well as technique of their estimation, can be applied in an arsenal of the tests for professional psychophysiological selection of the operators, which activity is connected to management of moving dynamic objects, processing of the information at deficiency of time etc. PMID- 11758478 TI - [The use of veterinary drugs during pregnancy of the dog]. AB - To point out which antibiotics and NSAIDs are safe to use during pregnancy of the dog and which are not, a simple system for classification has been developed for veterinarians. To find out more information about what drugs and during what stage of pregnancy veterinarians prescribe, a random survey was carried out among veterinarians who work primarily with companion animals. To develop this system for classification, literature concerning the teratogenicity of veterinary drugs was evaluated. The results of the survey indicate that the possibility of a pregnancy is rarely taken into account when prescribing medications and that many drugs that have not been proven safe, are prescribed. From the evaluation of literature follows that benzylpenicillin, amoxicillin with or without clavulanic acid, cefadroxil, cefalexin and lincomycin are the safest and therefore the agents of choice during pregnancy. It would be better if NSAIDs were not to be used during the last stage of pregnancy, because they might cause delay of the delivery. Drugs that might be teratogenic should be avoided unless there is no alternative and the possible benefits for the bitch outweigh the risks for the foetus. PMID- 11758479 TI - [Society's opinion]. PMID- 11758480 TI - [VFFT: forty years young, still going strong]. PMID- 11758481 TI - [Interview with Dr. Ingrid van der Gaag. 'Fortunately, I don't need much sleep.' (Interview by Sophie Deleu)]. PMID- 11758482 TI - [GGG around the Netherlands. Discussion with members serves as basis for agenda]. PMID- 11758483 TI - [Paratuberculosis program in the Netherlands. Animal husbandry most important weapon in prevention and therapy of paratuberculosis]. PMID- 11758484 TI - [Legal questions at the death bed. Patient self-determination gains more emphasis]. PMID- 11758485 TI - [Hepatitis C. What is established?]. PMID- 11758486 TI - [Virtual large intestine imaging with multi-level CT. Pain free coloscopy--that works!]. AB - Provided that the bowel is carefully cleansed, virtual colonoscopy permits a safe, reliable and painfree diagnosis of the large bowel. It requires distension of the bowel with ambient air. Contraindications include pregnancy, acute inflammation of the bowel and recent surgery. Tumors and large polyps (10 mm and more) can be diagnosed with certainty, while polyps measuring 5 mm and more are detected with a high degree of sensitivity. It goes without saying that virtual colonoscopy does not allow for the taking of biopsy material or the performance of therapeutic measures, so that positive or suspicious findings must be clarified by conventional colonoscopy. In principle, virtual colonoscopy is also suitable for use as a screening procedure. Whether the radiation exposure associated with the conventional examination protocol can be considered acceptable for screening purposes is questionable. However, using mathematical means, the radiation dose can be reduced to one-tenth of the usual dose. PMID- 11758487 TI - [Less sensitive, also uncomfortable, altogether more expensive. Virtual colonoscopy also has weaknesses]. PMID- 11758488 TI - [Emergencies in general practice. Acute gastroenteritis]. PMID- 11758489 TI - [Restless legs syndrome. Guidelines for diagnosis and therapy]. PMID- 11758490 TI - The decade of the brain at the C. Mondino Foundation. Ten years of research in experimental neurobiology (1990-2001). Pavia, Italy, June 24-26, 2001. Abstracts. PMID- 11758491 TI - Proceedings of the 9th International Symposium of Nephrology. Montecatini, Italy. October 25-27, 1999. PMID- 11758492 TI - [Proceedings of the All-Russian Conference "21st Century: up-to-date goals in morphology" and the Symposium "Morphological and Ecological Problems of Pulmonology". Saratov, September 12-14, 2001]. PMID- 11758494 TI - Research in Medical Education. Proceedings of the 40th annual conference. Washington, DC, USA. November 4-7, 2001. PMID- 11758493 TI - Retraction. PMID- 11758495 TI - Quality of life in patients after meningioma resection. PMID- 11758496 TI - The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. 1949. PMID- 11758497 TI - Bibliography. Current world literature. Myositis and myopathies. PMID- 11758498 TI - Bibliography. Current world literature. Raynaud phenomenon, scleroderma, overlap syndromes, and other fibrosing syndromes. PMID- 11758499 TI - Epitope specificity of mouse immune response on short polypeptides isolated from Viscum album. PMID- 11758500 TI - Optimising the Role of Herceptin in Breast Cancer. Symposium proceedings. Monte Carlo, June 19-21, 2000. PMID- 11758501 TI - Aminosalicylate as prophylaxis for Crohn's disease. PMID- 11758502 TI - Probiotics in IBD. PMID- 11758503 TI - Probiotics in Crohn's disease. PMID- 11758504 TI - Survey of informed consent for endoscopy. PMID- 11758505 TI - Why measure thiopurine methyltransferase activity? Direct administration of 6 thioguanine might be the alternative for 6-mercaptopurine or azathioprine. PMID- 11758506 TI - Multidrug resistant tuberculosis. PMID- 11758507 TI - Cost of physiotherapy in CF. PMID- 11758508 TI - Systemic effects of inhaled steroids. PMID- 11758509 TI - Systemic effects of inhaled steroids. PMID- 11758510 TI - Pulmonary infiltrates in non-HIV patients. PMID- 11758511 TI - Severe bullous emphysema associated with cocaine smoking. PMID- 11758512 TI - Side effects of antituberculosis treatment. PMID- 11758513 TI - [Blood and plasma transfusions in obstetrics. 1946]. PMID- 11758514 TI - Removal of slowly biodegradable COD in combined thermophilic UASB and MBBR systems. AB - Starch, cellulose and polyvinyl alcohol (PVA) are common substrates of the slowly biodegradable COD (SBCOD) in industrial wastewaters. Removal of the individual and mixed SbCOD substrates was investigated in a combined system of thermophilic upflow anaerobic sludge blanket (TUASB) reactor (55 degrees C) and aerobic moving bed biofilm reactor (MBBR). The removal mechanisms of the three SBCOD substrates were quite different. Starch-COD was almost equally utilized and removed in the two reactors. Cellulose-COD was completely (97-98%) removed from water in the TUASB reactor by microbial entrapment and sedimentation of the cellulose fibers. PVA alone was hardly biodegraded and removed by the combined reactors. However, PVA-COD could be removed to some extent in a binary solution of starch (77%) plus PVA (23%). The PVA macromolecules in the binary solution actually affected the microbial activity in the TUASB reactor resulting accumulation of volatile fatty acids, which shifted the overall COD removal from the TUASB to the MBBR reactor where SBCOD including PVA-COD was removed. Since the three SBCOD substrates were removed by different mechanisms, the combined reactors showed a better and more stable performance than individual reactors. PMID- 11758515 TI - Withdrawing life sustaining treatment and euthanasia debate. Euthanasia may be ethical, but it is not legal. PMID- 11758516 TI - Withdrawing life sustaining treatment and euthanasia debate. Doctrine of double effect should be discarded. PMID- 11758517 TI - Withdrawing life sustaining treatment and euthanasia debate. Double effect is different from euthanasia. PMID- 11758518 TI - Withdrawing life sustaining treatment and euthanasia debate. Role of paralysis during withdrawal of care needs clarifying, not polarising. PMID- 11758519 TI - Withdrawing life sustaining treatment and euthanasia debate. Neuromuscular blockade must be used with adequate sedation and analgesia. PMID- 11758520 TI - Cannabinoids in pain management. Cannabinoid receptor agonists will soon find their place in modern medicine. PMID- 11758521 TI - Cannabinoids in pain management. Few well controlled trials of cannabis exist for systemic review. PMID- 11758522 TI - Cannabinoids in pain management. Spasticity is not the same as pain. PMID- 11758523 TI - Collaboration with the Campbell collaboration. The Campbell principles are applied in West Midlands through public health research forum. PMID- 11758524 TI - Collaboration with the Campbell collaboration. EPPI centre reviews will aim to disseminate systematic reviews in education. PMID- 11758525 TI - Harvesting organs from recently executed prisoners. Practice must be stopped. PMID- 11758527 TI - The KMA Patient Safety Task Force develops materials to aid physicians. PMID- 11758526 TI - Harvesting organs from recently executed prisoners. Opportunities to offer support to members from the China Medical Association have been limited. PMID- 11758529 TI - [Complex regional pain syndrome: changing concepts and management strategies]. AB - The diagnosis of chronic regional pain associated with signs of dysautonomy is based exclusively on clinical criteria. The causal role of the sympathetic system being not established, the usual term "reflex sympathetic dystrophic syndrome" has been replaced by "complex regional pain syndrome". At present, no therapeutic option is validated as being specifically efficient. A controlled randomized trial is mandatory to establish efficacy and safety of a potential treatment. PMID- 11758528 TI - [Stellate ganglion radiofrequency neurolysis under CT guidance. Preliminary study]. AB - Sympathetically maintained pain syndrome of the upper limb is difficult to treat even with high doses of specific medication. Stellate ganglion block by in situ injection of a local anesthetic is an efficient and accepted method for diagnosis and treatment. The sedative effect is however transitory linked to the short effect of the drug. CT guidance, displaying an excellent contrast between soft tissues, bones, vessels and nerves, is a well suited and safe mean of guidance. Seven patients suffering from reflex sympathetic dystrophy were treated by stellate ganglion radiofrequency (RF) neurolysis at two sites (C7 and T1). Patients were evaluated for pain before and immediately after the procedure and at three months. Four patients had a significant (50%) pain relief lasting at 3 month. One patient had a temporary pain (one week) and 2 no pain relief. No patient had a Horner syndrome. One patient had a temporary neuralgia of surrounding nerves (brachial plexus). RF neurolysis of stellate ganglion under CT guidance is precise and appears efficient but further investigation on a larger cohort of patients is needed. PMID- 11758530 TI - [The centenary of the first Nobel prize in radiology: November 1901-2001]. PMID- 11758531 TI - [Contribution of one century of X-rays to medicine]. AB - In order to commemorate the centenary of the attribution of Nobel prizes in sciences, we present in this article a short description of the interaction of X rays with materials and a bibliography of 33 Nobel prize winners (6 for medicine, 18 in chemistry and 9 in physics) whose work is connected to applications of X ray interactions for medical and pharmaceutical purposes, and additionally of 12 Nobel prize winners in physics for their initiative in the discovery of particles which were recently used for medicine. PMID- 11758532 TI - Preterm premature rupture of the membranes before viability. AB - Although relatively uncommon, VPPROM remains a devastating complication of pregnancy. Current management options offer some hope of improved survival, but morbidity and mortality remain high. Counseling the patient and family following this diagnosis is challenging, and often requires input from both perinatal and neonatal staff. For those patients choosing expectant management who then reach viability, tertiary care should be considered to improve survival risks. PMID- 11758534 TI - Abstracts of the 9th European Symposium on Urolithiasis. September 13-15, 2001. Rotterdam, the Netherlands. PMID- 11758535 TI - Evidence-based medicine in primary care. PMID- 11758533 TI - [Role of levofloxacin in the treatment of urinary tract infections]. AB - The treatment of urinary tract infections (UTIs) and prostatitis has to be tailored on the clinical features of patients. UTIs should be differentiated in uncomplicated UTIs, acute pyelonephritis, complicated UTIs and UTIs in men, and asymptomatic UTIs. Prostatic inflammatory disease can be divided in 5 categories. Uncomplicated UTIs should be treated with a 3-day course of oral antibiotics, pyelonephritis and complicated UTIs with a 14-day course of oral antibiotics. In the case of high fever with chills intensive treatment with an appropriate antibiotic administered intravenously is needed until subsidence of the acute symptoms. This should be followed by oral antibiotic for two weeks. The treatment of asymptomatic UTIs should be considered for children and pregnant women. Antibiotics should be administered for 14-42 days in category I to IIIA of inflammatory prostatic disease. In the last decade acquired resistance of uropathogens to aminopenicillins and trimethoprim-sulfamethoxazole appears to have been increasing in the United States and Europe, while the susceptibility to systemic fluoroquinolones has remained unchanged at 98-99%. Particularly levofloxacin showed activity against Gram-positive bacteria without loss of Gram negative spectrum. In normal adults levofloxacin reached urinary, bladder and prostate concentrations after a 250 mg oral dose above the MIC90 for all typical uropathogens. Multicenter clinical studies on clinical and microbiological efficacy of levofloxacin were carried out in the treatment of genitourinary tract infections. Levofloxacin 250 mg once daily for three days was highly effective in the treatment of uncomplicated UTIs. Levofloxacin 250 mg once daily for 7-10 days was clinically and microbiologically effective also for the treatment of acute pyelonephritis and complicated UTIs. In patients with nonchlamydial chronic prostatitis the bacteriological response was 85.4%. Finally levofloxacin showed a superior tolerability profile than other fluoroquinolones. PMID- 11758536 TI - Frontiers in MMP (matrix metalloproteinases) and ADAMs (a disintegrin and metalloproteinase) research. October 17-19, 2001. Tokyo, Japan. Abstracts. PMID- 11758538 TI - Danish pacemaker and ICD register. 1999. PMID- 11758537 TI - Consensus meeting on systems for reporting results in acoustic neuroma. November 7-9, 2001. Tokyo, Japan. Abstracts. PMID- 11758539 TI - References to contemporary papers on acoustics. PMID- 11758540 TI - Abstracts of The New Food and Nutrition Conference. October 16-19, 2000. PMID- 11758541 TI - American Society for Reproductive Medicine 56th annual meeting. October 21-26, 2000. San Diego, California, USA. Abstracts. PMID- 11758542 TI - Re: World congress in Winnipeg. PMID- 11758543 TI - Cranial ultrasound detection of white matter echolucencies. PMID- 11758544 TI - Image of the month: malignant lymphomatous polyposis. PMID- 11758545 TI - Hering of the canals of Hering. PMID- 11758546 TI - Is the natural history of hepatitis C virus carriers with normal aminotransferase really benign? PMID- 11758547 TI - Management of irritable bowel syndrome. PMID- 11758548 TI - Unexpected low incidence of oral lichen planus in an HCV hyperendemic area of southern Italy. PMID- 11758549 TI - Gallbladder disease: acalculus or not? PMID- 11758551 TI - Abstracts of the 10th Congress of the European Academy of Dermatology and Venereology. 10-14 October 2001. Munich, Germany. PMID- 11758550 TI - Comments on experimental use of intravenous cyclosporine (CsA) alone to treat severe ulcerative colitis. PMID- 11758553 TI - Abstracts of the British Pharmacological Society meeting. 3-5 July 2001. University College Dublin. PMID- 11758552 TI - Lipid management guidelines--2001. National Heart Foundation of Australia, The Cardiac Society of Australia and New Zealand. PMID- 11758554 TI - If it's regulated like a duck ... uncertainties in implementing the patent exceptions of the Drug Price Competition and Patent Term Restoration Act. PMID- 11758555 TI - Will FDA relinquish the "gold standard" for new drug approval? Redefining "substantial evidence" in the FDA Modernization Act of 1997. PMID- 11758556 TI - The potential for self-interested behavior by pharmaceutical manufacturers through vertical integration with pharmacy benefit managers: the need for a new regulatory approach. PMID- 11758557 TI - FDAMA update. PMID- 11758558 TI - Structure/function claims in dietary supplement labeling: not all of these claims need to be submitted to FDA and accompanied in labeling by the DSHEA disclaimer. PMID- 11758559 TI - An overview from the Director of the Center for Food Safety and Applied Nutrition. PMID- 11758560 TI - The new RAC: restructuring of the National Institutes of Health recombinant DNA Advisory Committee. PMID- 11758561 TI - The SPS agreement of the World Trade Organization and the international trade of dairy products. PMID- 11758562 TI - Sublicense or supply agreement? Supreme Court of Canada interpretation benefits generic pharmaceutical industry. PMID- 11758563 TI - When unexpected government agents drop in: responding to requests for immediate interviews. PMID- 11758564 TI - Transmembrane auxin carrier systems--dynamic regulators of polar auxin transport. AB - Recent investigations of the biochemistry, physiology and molecular genetics of polar auxin transport have greatly advanced our understanding of the process and of the part it plays in the regulation of development and in the responses of cells, tissues and organs to internal and external stimuli. The molecular and physiological characterization of mutants which exhibit lesions in polar auxin transport has led to the isolation and sequencing of genes which encode putative components of auxin carrier systems, or proteins which directly or indirectly regulate these systems. This work has revealed that specific auxin uptake and efflux carriers are coded not by single genes, but by whole families of genes, the expression of which is tissue or stimulus specific. Furthermore, evidence is accumulating rapidly that at least the auxin efflux carrier is a multi-component system consisting of both catalytic and regulatory subunits, including a separate phytotropin-binding protein. Other genes have been tentatively identified which code proteins that regulate the expression of genes coding auxin carrier components, or which regulate the intracellular traffic or activity of auxin carriers. Investigations of the turn-over and Golgi-mediated trafficking of auxin carrier proteins have revealed that essential components of at least the efflux carrier have a very short half-life in the plasma membrane and are replaced without the need for concurrent protein synthesis, leading to speculation that they might cycle between internal stores and the plasma membrane. The way is now clear for the development of specific molecular probes with which to investigate the intracellular transport and targeting of auxin carrier proteins. PMID- 11758565 TI - A composite reference section for terminal proterozoic strata of southern Namibia. AB - Integrated sequence stratigraphic and chemostratigraphic data yield a framework for correlations of stratigraphic units in the terminal Proterozoic to Cambrian Witvlei and Nama Groups of Namibia. Coupled with precise U-Pb zircon age constraints, these correlations make it possible to construct a composite reference section for use in calibrating terminal Proterozoic chronostratigraphy. The Namibian reference section starts with two distinct glacial horizons and extends up to within 1 million years of the Proterozoic-Cambrian boundary. The two glacial horizons may represent each of two distinct Varanger-age glaciations better known from the North Atlantic region. From the higher of the two glacial horizons up, the composite stratigraphy preserves one of the thickest and most complete available records of carbon-isotope variability in post-Varanger terminal Proterozoic seawater. Four carbon-isotope chemostratigraphic intervals are recognized: (1) a postglacial negative delta 13C excursion (Npg interval); (2) a rising interval (Pr interval) of increasing positive delta 13C values; (3) a falling interval (Pf interval) characterized by decreasing positive delta 13C and culminating in near zero or negative values; and (4) an interval of moderately positive, relatively invariant delta 13C values (I interval) that extends up to the unconformity that contains the Proterozoic-Cambrian boundary. Each of these chemostratigraphic intervals can be recognized in widely separated correlative sections around the world. By comparing sediment accumulation rate in the radiometrically calibrated Namibian stratigraphy with sediment accumulation rates in correlative sections in Arctic Canada and Oman, a maximum age of 564 Ma is estimated for the end of the younger Varanger glaciation, 25 m.y. younger than previous estimates. PMID- 11758566 TI - Comparison of optokinetic scene effects on the somatogyral illusion. AB - The objective of this study was to determine during rotation the relative importance of a scene in achieving "visual dominance" over non-visual vestibular orientation inputs, e.g., otolith and semicircular canals. Five visual scenes were presented, while rotating the subject (at three angular acceleration rates), to obtain the vestibular and optokinetic nystagmus and perception of rotation. The onset time and direction of rotation, as well as EOG and chair velocity were recorded. Adaptation times during rotation at constant angular velocity and during post-rotation were also recorded. Analysis of perceived times (onset, adaptation, and post-rotatory adaptation) with the EOG slow-phase velocity at respectively perceived times were analyzed using the SAS procedures Analysis of Variance (ANOVA) and General Linear Models (GLM). Basic hypotheses for the study were: "There are no differences in latencies for either onset time (L1), adaptation to rotation (L2), or adaptation to post rotatory motion (L4), between treatment conditions, or between Groups of subjects, or between acceleration rates, between constant rotation velocities, or between direction of rotation." From the results, it was concluded that pilots are highly visually dependent; additionally, if there is a sensory conflict, a larger percentage of individuals (pilots) will follow visual perceptions even if the demands of the aerial environment and our perception is incorrect. However, in sensory conflict conditions, with degraded visual scene individuals including pilots will revert to vestibular perception rather than visual perception (less visually coupled), approaching percentages as noted with a dark environment. PMID- 11758567 TI - The role of rehabilitation in the treatment of balance disorders. AB - The vestibular system registers changes in head position, gravity, vibration, acceleration and deceleration. This information is then transmitted to the central nervous system, where additional information from the visual and auditory systems, muscles, tendons, joints and skin, serve to regulate and maintain the equilibrium and orientation of the system. Vision plays the most obvious part in continual monitoring of the environment. Distances, speeds of linear and angular movement, and changes of direction, can all be estimated with experience and be integrated in the central nervous system with those received by other sensory systems. Light touch and pressure receptors in the skin detect bodily contact with the environment and are an essential source of data in walking, cycling, motoring, flying and other activities. Proprioception provides data regarding the instantaneous mechanical disposition of the musculoskeletal system as it relates to the force of gravity acting upon it. The functional recovery that occurs after unilateral vestibular lesions is referred to as "vestibular compensation" and consists of all the processes of neurological reorganization that allow recovering balance after a unilateral vestibular lesion. Exercises are particularly useful in helping patients to overcome disturbances, associated with balance disorders. The purpose of these selected exercises is to build up a tolerance mechanism in the brain, which will compensate for the unequal balance of the two ears. PMID- 11758568 TI - Effect of simulated and real weightlessness on early regeneration stages of Brassica napus protoplasts. AB - Results from experiments using protoplasts in space, performed on the Biokosmos 9 satellite in 1989 and on the Space Shuttle on the IML-1-mission in 1992 and S/MM 03 in 1996, are presented. This paper focuses on the observation that the regeneration capacity of protoplasts is lower under micro-g conditions than under 1 g conditions. These aspects have been difficult to interpret and raise new questions about the mechanisms behind the observed effects. In an effort to try to find a key element to the poor regeneration capacity, ground-based studies were initiated focusing on the effect of the variable organization and quantity of corticular microtubules (CMTs) as a consequence of short periods of real and simulated weightlessness. The new results demonstrated the capacity of protoplasts to enter division, confirming the findings in space that this was affected by gravity. The percentage of dividing cells significantly decreased as a result of exposure to simulated weightlessness on a 2-D clinostat. Similar observations were made when comparing the wall components, which confirmed that the reconstitution of the cell wall was retarded under both space conditions and simulated weightlessness. The peroxidase activity in protoplasts exposed to microgravity was slightly decreased in both 0 g and 1 g flight samples compared with the ground controls, whereas activity in the protoplasts exposed to simulated weightlessness was similar to activity in the 1 g control. The observation that protoplasts had randomized and more sparse corticular microtubules when exposed to various forms of simulated and real weightlessness on a free-fall machine on the ground could indicate that the low division capacity in 0 g protoplasts was correlated with an abnormal CMT array in these protoplasts. This study has increased our knowledge of the more basic biochemical and cell biological aspects of g effects. This is an important link in preparation for the new space era, when it will be possible to follow the growth of single cells and tissue cultures for generations under microgravity conditions on the new International Space Station, which will be functional on a permanent basis from the year 2003. PMID- 11758569 TI - Leg venous compliance in orthostatic intolerance before and after 14-day head down bed rest. AB - To test the hypothesis that increased leg venous compliance (LVC) is one of the contributory factors to orthostatic intolerance (OI) after simulated microgravity, 28 healthy young males were exposed to a 14-day head-down bed rest, and LVC was measured by venous occlusion plethysmography. Orthostatic tolerance was evaluated by a 60 degree head-up tilt (HUT) for 15 min. Sixteen subjects suffered from OI after the bed rest. They were then divided into orthostatic tolerance (non-fainters, n=12) and intolerance (fainters, n=16) groups. We found that fainters had significantly larger LVC before bed rest (0.055 +/- 0.003 vs. 0.065 +/- 0.002 ml 100 ml-1 mm Hg-1, non-fainter vs. fainter; P < 0.05). After bed rest, LVC markedly increased in both groups. In all the subjects calf circumference was reduced on average by 4.7% and the percent change in LVC was negatively correlated with the percent change in calf circumference when all subjects' data were combined after bed rest (r = -0.42, P < 0.05). Our results did not support the hypothesis that increased LVC is the contributory factor to OI after a 14-day bed rest; however, the mechanisms behind the large LVC in the fainters before bed rest are unclear, and the initial LVC might be a predictive indicator for OI after microgravity exposure. PMID- 11758570 TI - Dispersal and parasitizing abilities of Eupelmus vuilleti (Hymenoptera: Eupelmidae) within a column of cowpea seeds. AB - Eupelmus vuilleti (Crawford) is an ectoparasitoid of the seed-eating beetle Bruchidius atrolineatus (Pic), which is an important pest of stored cowpea, Vigna unguiculata Walp, seeds in West Africa. Herein, we investigated the dispersal abilities of females within columns of seeds to assess the potential of E. vuilleti as a biological control agent of bruchids in cowpea granaries. The influence of host presence together with the 2 abiotic factors light and gravity on parasitoid movement and parasitization efficiency were analyzed. E. vuilleti females were able to travel through large seed masses and parasitize hosts located at the end of the seed column opposed to their introduction zone. Parasitoid movement was stimulated by light. E. vuilleti females exhibited a negative geotropism. Females introduced at the bottom of the seed column dispersed more and parasitized more hosts than females introduced at the top. Host presence had some influence on the dispersal of the parasitoids within the seed column at a host density of 10 infested seeds for 16,000-18,000 uninfested seeds. This depended on female introduction zone because gravity was the major factor influencing dispersal. The possible applications of these results for biological control of bruchids in cowpea granaries are discussed. PMID- 11758571 TI - ESA payloads and experiments on the Foton-12 mission. AB - The international Foton-12 mission in September 1999 was a milestone in terms of payload mass, complexity and scientific diversity. ESA's contribution amounted to an unprecedented 240 kg--almost half of Foton's total payload. The Agency's 11 experiments covered fluid physics, biology, radiation dosimetry, materials science and meteoritics. This article describes the mission from an ESA perspective and highlights the initial results. PMID- 11758572 TI - Overview of the Hatch-Waxman Act and its impact on the drug development process. PMID- 11758573 TI - FDA's role in making exclusivity determinations. PMID- 11758574 TI - The role of the patent and trademark office under 35 U.S.C. section 156. PMID- 11758575 TI - FDA's role in administering the Hatch-Waxman Act. PMID- 11758576 TI - Patent issues that both regulatory affairs personnel and patent attorneys should understand. PMID- 11758577 TI - Originator drug development. PMID- 11758578 TI - The Hatch-Waxman Act during patent prosecution and beyond. PMID- 11758579 TI - Biotechnology and patent term extension issues. PMID- 11758580 TI - The biotechnology industry organization's view on Hatch-Waxman reform. PMID- 11758581 TI - Market exclusivity after a prescription to nonprescription drug switch: striking the right balance between innovation and competition. PMID- 11758582 TI - Patenting drug products: anticipating Hatch-Waxman issues during the claims drafting process. PMID- 11758583 TI - NASA Safety and Health (Short Form). Final rule. AB - This final rule adopts with changes the interim rule published in the Federal Register on April 5, 2001 (65 FR 18051-18053), which amended the NASA FAR Supplement to implement a Safety and Health (Short Form) clause to address safety and occupational health in all NASA contracts above the micro-purchase threshold where the existing Safety and Health clause did not apply, and amended other safety and health clauses to be consistent with the new NASA Safety and Health (Short Form) clause. PMID- 11758584 TI - Veterans Benefits and Health Care Improvement Act of 2000. Final rule. AB - This document amends various Department of Veterans Affairs(VA) regulations concerning the definition of the term "active military, naval, or air service"; the payment limitation based on the value of certain incompetent veterans' estates; the plot allowance for certain individuals buried in State veterans' cemeteries and the limitation on payment of pension for certain recipients of Medicaid-covered nursing home care. The amendments are necessary to reflect statutory changes contained in the Veterans Benefits and Health Care Improvement Act of 2000. PMID- 11758585 TI - Guidance and justification in particularistic ethics. AB - This paper argues that, contrary to a common line of criticism followed by scholars such as Helga Kuhse, a particularistic version of virtue ethics properly elaborated, can provide sound moral guidance and a satisfactory account for moral justification of our opinions regarding, for instance, health care practice. In the first part of the paper, three criteria for comparing normative theories with respect to action-guiding power are outlined, and it is argued that the presented particularistic version of virtue ethics actually can provide more guidance than the universalistic theories followed by Kuhse and others. In the second part of the paper it is claimed that universalist normative theories have serious problems accounting for the role that moral principles are supposed to play in the justification, of moral opinions, whereas the present version of virtue ethics accommodates a plausible alternative idea of justification without invoking moral principles or eschewing objectivity. PMID- 11758586 TI - Informed consent, exploitation and whether it is possible to conduct human subjects research without either one. AB - Clinical research with adults who are unable to provide informed consent has the potential to improve understanding and care of a number of devastating conditions. This research also has the potential to exploit some of society's most vulnerable members. Recently, a number of task forces and individual writers have proposed guidelines to ensure that such research is both possible and ethical. Yet, there is widespread disagreement over which safeguards should be adopted. In the present paper, I consider to what extent these disagreements can be resolved by appeal to a general account of the interests of subjects who are unable to consent and the conditions that must be satisfied for research enrollment to constitute exploitation of their inability to make their own decisions. PMID- 11758587 TI - Infanticide and the liberal view on abortion. AB - Mary Anne Warren provides a well-known defense of the liberal position in the abortion debate, yet her argument is subject to the objection that it implies that infanticide is morally permissible. In a postscript to her original article, Warren argues that her position does not commit her to the moral acceptability of infanticide. I argue that the reasoning Warren presents in her postscript on infanticide undermines her original main argument in support of the liberal view: she cannot use this argument to both defend the liberal view on abortion and establish that infanticide is morally wrong. PMID- 11758588 TI - The moral difference between infanticide and abortion: a response to Robert Card. PMID- 11758589 TI - From the editors. PMID- 11758590 TI - Pretax allotments for health insurance premiums. Final rule. AB - The Office of Personnel Management (OPM) is issuing final regulations dealing with the use of OPM's allotment authority to allow for Federal Employees Health Benefits (FEHB) employee premium payments to be deducted on a pretax basis under section 125 of the Internal Revenue Code. The allotment regulations work in tandem with related FEHB regulations dealing with this premium conversion. PMID- 11758591 TI - Suspension of TRICARE-eligible's enrollment in the Federal Employees Health Benefits (FEHB) Program. Interim rule. AB - The Office of Personnel Management is issuing an interim rule to allow TRICARE eligible FEHB Program annuitants and former spouses to suspend their FEHB enrollments, and then return to the FEHB Program during the Open Season, or return to FEHB coverage immediately, if they involuntarily lose TRICARE coverage. The intent of this rule is to allow TRICARE-eligible beneficiaries to avoid the expense of continuing to pay FEHB Program premiums while they are using TRICARE coverage, without endangering their ability to return to the FEHB Program in the future. PMID- 11758592 TI - Compliance alternatives for provision of uncompensated services. Final rule. AB - The rules below revise a compliance alternative applicable to health care facilities with Hill-Burton uncompensated services obligations. The revised compliance alternative provides a more flexible compliance standard for facilities that principally serve nonpaying patient populations by reducing the amount of time needed to qualify for certification under the alternative and by providing for a provisional certification, where a facility is unable to qualify for full certification. The rules below also provide a compliance alternative for obligated facilities with histories of uncompensated services deficits, to enable them to make up the deficits ona timely basis. These revisions have the effect of making it easier for facilities with uncompensated services obligations to meet those obligations, while still ensuring the availability of uncompensated services to persons unable to pay. PMID- 11758593 TI - Applied ethics: what kind of ethics and what kind of ethicist? AB - Types of ethics are classified as more or less holistic in three respects. Current forms of applied ethics (among them reflective equilibrium) are criticized for being reductionist rather than holistic. It is claimed that applied ethics ought to be of a holistic kind. Two examples (tracing of hereditary cancer and active euthanasia) are used for maintaining that a reductionist ethic is of limited use for solving practical moral problems. Some possible roles of the ethicist are discussed. It is maintained that the ethicist ought to be a life philosopher mapping the moral landscape or a personal mentor rather than being a policeman or an ethics engineer. PMID- 11758594 TI - Autonomy and the psychiatric patient. AB - The aim of this paper is to consider possible justifications for the denial of the right to refuse treatment in the case of certain kinds of psychiatric patients. The basis of this right in general is first considered: arguments based on Kantian conceptions of autonomy are rejected as confused, and preference is given to Millian arguments based on the right to make decisions about one's own life, however irrational, as long as they do not harm others. In light of this discussion, it is argued that mentally disordered people cannot be denied this right on grounds of their 'irrationality', which is anyway a vague concept with several meanings. In conclusion, it is argued that there may be a case for such a denial in those sorts of mental disorder which involve a 'disturbance of personal identity'. PMID- 11758595 TI - A Kantian argument for a duty to donate one's own organs. A reply to Nicole Gerrand. AB - Nicole Gerrand is right to criticize Munzer for not connecting a person's dignity to the "capacity to exhibit humanity by acting rationally." However, connecting these does not mean that they are one and the same concept. Gerrand fails to make two distinctions that are decisive in the context of Kant's ethics. First, she does not distinguish between vital organs, integral organs and mere "accumulations", each of which requires a specific moral argument. Second, she does not distinguish between human rational nature in itself, or the capacity to have free will, and the possibility of action rationally, or freedom of choice. Having drawn these distinctions, I argue that Kant's own principles fully allow certain kinds of organ transplants such as blood, skin and marrow transplants from living bodies as well as the transplantation of both vital organs and essential organs from fresh corpses. In fact, Kant's own moral principles should make of these an enforceable duty of right. Unlike Gerrand, then, I think that the question of whether or not donors should be paid--and the patient should pay- is a key issue even in a Kantian context. PMID- 11758596 TI - Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over the-counter human use; partial final rule for combination drug products containing a bronchodilator. Final rule. AB - The Food and Drug Administration (FDA) is issuing a final rule establishing that cough-cold combination drug products containing any oral bronchodilator active ingredient in combination with any analgesic(s) or analgesic-antipyretic(s), anticholinergic, antihistamine, oral antitussive, or stimulant active ingredient are not generally recognized as safe and effective and are misbranded for over the-counter (OTC) use. FDA is issuing this final rule after receiving no public comments on the agency's proposed nonmonograph status of these specific combination drug products, which was issued in the form of a tentative final monograph for OTC cough-cold combination drug products. This final rule is part of the ongoing review of OTC drug products conducted by FDA. PMID- 11758597 TI - Medicare program; civil money penalties, assessments, and revised sanction authorities. Final rule with comment period. AB - This final rule with comment period is a technical rule that updates our civil money penalty (CMP) regulations to add CMP authorities already enacted as part of the Balanced Budget Act of 1997 (BBA) and delegated to us. The rule delineates our authority to assess penalties for: failure to bill outpatient therapy services or comprehensive outpatient rehabilitation services (CORS) on an assignment-related basis, failure to bill ambulance services on an assignment related basis, failure to provide an itemized statement for Medicare items and services to a Medicare beneficiary upon his/her request, and failure of physicians or nonphysician practitioners to provide diagnostic codes for items or services they furnish or failure to provide this information to the entity furnishing the item or service ordered by the practitioner. The rule also contains technical changes to further conform our current CMP rules to changes in the statute enacted by the BBA. PMID- 11758598 TI - EDTA samples for the measurement of erythrocyte sedimentation rate using Sedimatic 100 analyser. PMID- 11758600 TI - XVIII Congress of the International Society on Thrombosis and Haemostasis (ISTH Congress). PMID- 11758599 TI - Gc-globulin in acute coronary syndrome. PMID- 11758601 TI - Symposium, coagulation monitoring: bringing the lab to the patient. PMID- 11758602 TI - Identifying bacteria in human urine: current practice and the potential for rapid, near-patient diagnosis by sensing volatile organic compounds. AB - Urinary tract infection (UTI) represents a significant burden for the National Health Service. Extensive research has been directed towards rapid detection of UTI in the last thirty years. A wide range of microbiological and chemical techniques are now available to identify and quantify bacteria in urine. However, there is a clear and present need for near, rapid, sensitive, reliable analytical methods, preferably with low-running costs, that could allow early detection of UTI and other diseases in urine. Here we review the "state of the art" of current practice for the detection of bacteria in urine and describe the advantages of the recent "e-nose" technology as a potential tool for rapid, near-patient diagnosis of UTI, by sensing volatile organic compounds (VOCs). PMID- 11758603 TI - Risk factors for coronary disease: the time for a paradigm shift? AB - Risk stratification is a key element of clinical management not only in the primary and secondary prevention, but also during the acute stages of cardiovascular disease. The current risk assessment algorithms in primary prevention are based on established risk factors: gender and age, cigarette smoking, the presence of hypertension and diabetes mellitus, and serum concentrations of total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein-cholesterol. However, many individuals who are assessed as "low risk" on the basis of traditional risk factors, still develop cardiac events. This article addresses current issues relevant to the assessment of cardiovascular risk. It emphasizes the potential importance of disturbed energy supply for atherogenesis, by introducing the concept of fuel transport (chylomicron, VLDL, and remnants) and overflow (LDL) pathways of lipid metabolism. It highlights the present lack of routine methods to monitor the fuel transport pathway. It considers the measurements of serum C-reactive protein and plasma fibrinogen as new additions to the cardiovascular risk factor profiles. Finally, risk stratification based on the traditional and the new risk factors is linked to that based on the markers of acute myocardial damage such as cardiac troponin I or troponin T. It is concluded that the combined use of the markers of myocardial damage and the "new" cardiovascular risk factors is the way ahead for the assessment of cardiovascular risk. PMID- 11758604 TI - Description of a generally applicable model for the evaluation of uncertainty of measurement in clinical chemistry. AB - There is a growing pressure on clinical chemistry laboratories to conform to quality standards that require the evaluation and expression of the uncertainty of results of measurement. Nevertheless, there is some reluctance to accept the uncertainty concept in the analytical community due to difficulty in evaluating uncertainty in practice. For example, often the uncertainty of some uncertainty components is not known very well in clinical chemistry measurements, such as those associated with matrix effects or with the values of the calibrators. Moreover, it is not clear how to interpret uncertainty in relation to diagnostic criteria, reference ranges and other decision limits in clinical chemistry practice. Hence, the value of reporting the uncertainty of the measurement result is not obvious. In this paper it is suggested a relatively simple, logical procedure for evaluating measurement uncertainty based on the principles in the Guide for the Expression of Uncertainty of Measurement (GUM). The measurement process is partitioned into elements that are well known to the analyst, namely sampling, calibration, and analysis. The corresponding model function expresses the result of a measurement as the value obtained by the analytical procedure multiplied by the correction factors for sampling bias, for bias caused by the calibrators, and for other types of bias. Under normal conditions, when the measurement procedure is validated and corrected for all known bias, the expected value of each correction factor is one. The uncertainty that remains with regard to sampling, manufacturing of calibrators and other types of bias is combined with the analytical imprecision to yield a combined uncertainty of a result of measurement. The advantages of this approach are: (i) Data from the method validation, internal quality control and from participation in external quality control schemes can be used as input in the uncertainty evaluation process. (ii) The partition of the measurement into well-defined tasks highlights the different responsibilities of the clinical chemistry laboratory and of the manufacturer of reagents and calibrators. (iii) The approach can be used to harmonize the uncertainty evaluation process, which is particularly relevant for laboratories seeking accreditation under ISO 17025. The application of the proposed model is demonstrated by evaluating the uncertainty of a result of a measurement of prolactin in human serum. In the example it is shown how to treat the uncertainty associated with a calibrator supplied with a commercial analytical kit, and how to evaluate the uncertainty associated with matrix effects. PMID- 11758605 TI - Nitric oxide in liver transplantation. AB - Liver transplantation is the only therapeutic option for patients with end-stage liver disease. Nitric oxide, a free radical produced from L-arginine, a potent vasodilator, also inhibits platelet adhesion and aggregation, reduces adhesion of leukocytes to the endothelium and suppresses proliferation of vascular smooth muscle cells. The inducible form of the nitric oxide synthase may generate large quantities of nitric oxide, and may be induced by the action of cytokines and lipopolysaccharides. Nitric oxide can be released from the hepatic vascular endothelium, platelets and Kupffer cells as a response to ischemia-reperfusion injury and circulatory shock. We analyzed the relationships between the levels of nitric oxide, hepatic enzymes and other clinical parameters (glucose, total proteins, total bilirubin, creatinine, albumin) obtained in serum samples before liver transplantation and every 48 h till day 15 in 15 patients aged 40 +/- 13 years. Aspartate aminotransferase and alanine aminotransferase levels changed from high at the beginning, to almost normal at the end of the study, cholinesterase levels remained decreased throughout the study and nitric oxide remained high, never reaching normal values. PMID- 11758607 TI - Determination of serum cortisol by isotope-dilution liquid-chromatography electrospray ionization tandem mass spectrometry with on-line extraction. AB - A liquid chromatographic-mass spectrometric method for the determination of cortisol in serum using atmospheric pressure electrospray ionization and tandem mass spectrometry is described. During sample preparation, 150 microl of serum were deproteinized with methanol/zinc sulfate followed by on-line solid phase extraction employing column switching. Tri-deuterated cortisol was used as the internal standard. The following transitions were monitored: cortisol, 363>309 m/z; d3-cortisol, 366>312 m/z. The total run-time was 5 minutes. The method proved linear (0-500 microg/l; r=0.999), precise (total coefficient of variation between 5.0% and 3.2% at a mean cortisol concentration of 15.1 microg/l and 269 microg/l, respectively; n=16) and specific with regard to relevant endogenous and exogenous steroids. PMID- 11758606 TI - Carbohydrate-deficient transferrin and chronic alcohol ingestion in subjects with transferrin CD-variants. AB - Carbohydrate-deficient transferrin (CDT) is widely accepted as screening test for excessive alcohol consumption. However, results from subjects with transferrin variants must be interpreted with caution since chromatography-based methods may give false-positive results. Furthermore, due to the co-elution in HPLC or the co migration in capillary zone electrophoresis (CZE) of the di- and trisialylated C transferrins with the tetrasialylated D peak, exact measurement of CDT is impossible in CD-variants. Therefore, in this study, we tried to offer a different solution, including only the asialo-D, asialo-C, monosialo-D, monosialo C, disialo-D and trisialo-D transferrins in the CDT calculation and referring to a different cut-off value for CDT in transferrin CD-variants. Comparison of alcohol consumers with teetotalers demonstrated area under the receiver operating characteristic curve of 0.79 and 0.76 for carbohydrate-deficient transferrin, 0.71 and 0.71 for mean corpuscular volume and 0.51 and 0.68 for gamma glutamyltransferase in 43 subjects with transferrin CD-variants and 225 subjects with CC-phenotypes, respectively. Since false-positive carbohydrate-deficient transferrin results due to a transferrin CD-variant have major social implications, capillary electrophoresis-based or similar methods (HPLC, FPLC) should be preferred in populations carrying a high D-allele frequency. PMID- 11758608 TI - Analysis of 5' non-coding region in hepatitis C virus by single-strand conformation polymorphism and low-stringency single specific primer PCR. AB - Single-strand conformation polymorphism (SSCP) and low-stringency single specific primer (LSSP)-PCR in hepatitis C virus (HCV) genotyping were examined for informativeness and reliability. The analysis of HCV isolates included seven type 1 isolates, two type 2 isolates, and two type 3 isolates. We also analyzed five isolates that presented as mixed infections determined by type-specific PCR. Among mixed isolates, one isolate was 1a/1b and four isolates were 1b/3a. SSCP and LSSP-PCR were applied to the analysis of 5' non-coding region of HCV (-289 to -5) that contains genotype-specific sequences. Direct cycle sequencing of this region determined sequence divergences that define genotype and sequence alterations within the same genotype. Optimized conditions for the SSCP analysis clearly distinguished between genotypes 1, 2 and 3. In addition, the SSCP analysis detected sequence variants within the same genotype. However, the SSCP analysis and DNA sequencing did not confirm the presence of mixed infections. LSSP analysis, not previously employed in HCV genotyping, enabled clear distinction between genotypes 1, 2 and 3, however, this method did not differentiate between sequence variants within a genotype. Importantly, the LSSP profile demonstrated distinction between mixed infection isolates. PMID- 11758609 TI - Rapid detection of the Wilson's disease H1069Q mutation by melting curve analysis with the LightCycler. AB - Wilson's disease is an inherited autosomal recessive disorder of copper transport characterized by progressive copper accumulation in the liver and the central nervous system. The disease is caused by mutations in the ATP7B gene. Although many different mutations in this gene were described, a substitution of a histidine by a glutamine residue at codon 1069 (H1069Q) accounts for approximately 30-60% of all mutations in Caucasian patients. We describe a DNA based method using fluorescence resonance energy transfer probes on the LightCycler for rapid determination of the common H1069Q mutation in the ATP7B gene. We screened 53 patients with Wilson's disease for the H1069Q mutation by the melting curve analysis. The reliability and discriminating power of this technique were documented by comparing results of the LightCycler assay with direct DNA sequencing. The protocol allows genotyping of 30 samples in less than 1 hour without a need for restriction enzyme digestion or gel electrophoresis. PMID- 11758610 TI - Persistent hepatitis G virus (HGV) infection in chronic hemodialysis patients and non-B, non-C chronic hepatitis. AB - Three groups of patients have been studied longitudinally for 24 months to analyze the role of hepatitis G virus (HGV) in hepatic disease. Group 1 consisted of 50 patients with non-B, non-C chronic hepatitis, group 2 consisted of 44 hemodialyzed patients, and group 3 consisted of 50 healthy blood donors. The presence of HGV RNA was detected by both reverse transcription-polymerase chain reaction (RT-PCR) and capillary zone electrophoresis (CZE). At the baseline visit the HGV RNA was detected in seven out of 50 patients with non-B, non-C chronic hepatitis, in two out of 44 hemodialyzed patients, and in three out of 50 healthy blood donors. HGV-infected hemodialyzed patients and HGV viremic blood donors had serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within normal limits. During the follow-up period the two HGV-positive hemodialyzed patients and the three infected healthy blood donors did not show any sign of hepatic disease. There were no significant differences between HGV positive patients in the three groups at the beginning and at the end of the follow-up. No considerable deterioration of general health conditions was observed on the basis of clinical and laboratory data in HGV-positive chronic hepatitis patients. Finally, HGV does not seem to be responsible for hepatic disease. PMID- 11758611 TI - Serum 90K/MAC-2BP glycoprotein in patients with liver cirrhosis and hepatocellular carcinoma: a comparison with alpha-fetoprotein. AB - Glycoprotein 90K/MAC-2BP is a member of the scavenger receptor cystein-rich protein superfamily, which is thought to be involved in immune surveillance, defending the body against pathogens and cancer. 90K serum levels are elevated in patients with cancer of various origins and in viral infections, such as human immunodeficiency virus and hepatitis C virus (HCV). Because in patients with HCV related cirrhosis the incidence of hepatocellular carcinoma (HCC) is high, in the present paper we examined, by means of an enzyme-linked immunosorbent assay, the 90K serum levels in 103 patients with liver cirrhosis, and in 69 with HCC, and compared them to alpha-fetoprotein, the reference tumor marker for this neoplasm. Serum levels of 90K (cut-off 14 microg/ml) were elevated both in cirrhosis (39%) and HCC (46%) compared to controls (14.1 microg/ml vs. 10.6 microg/ml in cirrhosis, and 14.8 microg/ml vs. 9.1 microg/ml in HCC, p < or = 0.001). There was a significant association with the presence of anti-HCV antibodies. 90K was found to be a non-specific tumor marker which is complementary to alpha fetoprotein on the basis of its probable different biological significance. In fact, 74% of HCC patients had at least one positive marker. Combined use of 90K and alpha-fetoprotein could improve the sensitivity of a single test in the diagnosis of HCC. PMID- 11758612 TI - Testing the predictability of the relative urinary supersaturation from the Bonn Risk-Index for calcium oxalate stone formation. AB - When introducing a new parameter, it is necessary to compare the power of the new measure with already established ones. For a new method it is quite difficult to compete with established methods which have already ascertained sets of data over many years. A formal comparison of the new parameter with the actual "gold standard" method can be a useful approach to reduce that problem. It cannot be expected that a new measure would reflect the "gold-standard" method in a simple proportionality. Therefore, it is important to find out the accuracy of the prediction of one parameter from the other, based on simple, e.g. linear, functions. A number of methods exist to determine the crystallization risk of calcium oxalate salts from urine. The most established method is the calculation of the relative urinary supersaturations with respect to these salts using the EQUIL-program, a program computing the equilibrium concentrations of complexes of primary cations and anions commonly found in urine. The Bonn-Risk-Index (BRI) is a new strategy for the evaluation of the risk of calcium oxalate formation, by performing crystallization experiments on native unprepared urine samples. Although the analytical and computational efforts of both approaches are quite different (relative supersaturation = high, BRI = low), the measurements revealed a considerable and significant linear relationship between the relative urinary calcium oxalate supersaturation, and BRI. We were, therefore, interested in predicting the relative supersaturation from the BRI and in the accuracy of this prediction. PMID- 11758613 TI - Reference values for the five electrophoretic serum protein fractions in Caucasian children by capillary zone electrophoresis. AB - We report age-related reference intervals for capillary zone electrophoresis for children between 1 and 14 years of age. PMID- 11758614 TI - Reference intervals from birth to adulthood for serum thyroxine (T4), triiodothyronine (T3), free T3, free T4, thyroxine binding globulin (TBG) and thyrotropin (TSH). AB - Disorders in thyroid function can impair normal development in children. Therefore it was our aim to establish reference intervals for serum triiodothyronine (T3), free T3 (fT3), thyroxine (T4), free T4 (fT4), thyroxine binding globulin (TBG) and thyrotropin (TSH) which are applicable from birth to adulthood by using the non-isotopic automated chemiluminescence immunoassay system, Immulite (DPC Los Angeles, USA). Serum samples from 762 euthyroid newborns, children and adolescents (369 female, 393 male; age 1 day to 19 years) were examined; of these, 381 were classified as pubertal. Due to non-normal distribution, the 2.5th, 50th and 97.5th percentiles (the central 95% interval) were calculated for each group. The median concentrations of T4, fT4 and TSH were up to 3.2-fold higher during the first 2 weeks, while T4 increased during the first month of life. The concentrations in all age groups showed no sex differences. From 1 year onwards, the concentration of all parameters tended to decrease until adult age, with the exception of TBG which increased by >60% (p<0.02) and reached a maximum at approximately 5 years of age. The findings underscore the fact that thyroid hormones are not associated with sexual development, except for TBG, which decreased slightly (p<0.04) between Tanner stages 1 and 5. However, the reference intervals established here demonstrate that marked changes occur in concentrations of thyroid hormones after the neonatal period. Our findings complement these of earlier studies. The developed reference intervals can be used to assess the thyroid status of patients, particularly if the measurements are done on the Immulite/Immulite 2000 system. PMID- 11758615 TI - Pediatric reference ranges for osteocalcin measured by the Immulite analyzer. AB - Pediatric reference ranges for osteocalcin measured by a new, fully automated, chemiluminescent immunometric assay on the Immulite immunoanalyzer are presented. Samples from 627 children, ranging from newborns to 18 years of age, were measured. Osteocalcin values are generally higher in children than in adults, highest levels being reached during the puberty growth spurt at about 12 years in girls and 14 years in boys, thereafter rapidly declining towards adult levels. PMID- 11758616 TI - False increase in serum C-reactive protein caused by monoclonal IgM-lambda: a case report. AB - Interference caused by human anti-animal antibodies has been described in many laboratory assays. Usually the antigen giving rise to these antibodies is not known. When present in sufficiently high titer, these antibodies may have a significant effect on laboratory assays, causing falsely increased or decreased values, to the detriment of patient care and laboratory diagnosis. We report a case of an 86-year old man who had greatly increased C-reactive protein (CRP) levels in serum (>500 mg/l), suggestive of an unusually strong inflammatory response such as seen in septicemia. Because this diagnosis was not consistent with his symptoms, CRP measurements were repeated using alternative methods, none of which gave CRP results higher than 12 mg/l. Protein electrophoresis followed by immunofixation showed a monoclonal IgM-lambda paraprotein (7 g/l), which bound the goat anti-CRP antibodies used in the first CRP assay. Precipitation of the IgM-lambda paraprotein eliminated the interference. Subsequent bone marrow tests did not reveal any blood malignancy, and the monoclonal IgM component was attributed to monoclonal gammopathy of unknown significance. In conclusion, an IgM-lambda paraprotein was shown to cause falsely elevated CRP values in an automated immunometric assay using goat anti-CRP antibodies. PMID- 11758617 TI - Key elements of the implementation of a quality system in three Finnish clinical laboratories. AB - The aim of the study was to discover how an implemented quality system succeeded in fulfilling the personnel and management expectations and to identify the factors that facilitate or hinder quality management implementation in clinical laboratories. The concepts assessed include leadership (commitment and change management), clear and common goals, human recourses focus, client focus, management by fact and process improvement. The quality process in the laboratories had not, even after 3-4 years, reached a level of acceptance allowing its use as a daily development tool. The factors that predict a success of the quality system include willingness to improve the laboratory services and to keep the process going and good atmosphere at work. However, the study showed that the senior managers of the laboratory should take a more visible role in leading the change, and emphasize more explicitly the long-term goals. The middle managers (physicians, biochemists and head technologists) should arrange opportunities for the staff to participate in the system and disseminate the information on, and practical applications of, the quality principles and tools. The staff should be more active in finding new information and in participating in the system. PMID- 11758618 TI - The temple and the plane tree: rationality and cult at the beginnings of western medicine. AB - There are multiple interrelationships between science, medicine and visual arts. This article discusses aspects of architecture associated with the Greek healing cult of Asklepios, the case in point being the Asklepios temple on the island of Kos in the Aegean. Further, the cult is contrasted with the beginnings of the observation-based medicine practised by Hippocrates (460-c.370 BC). Finally, it is suggested that including elements of visual arts in medical education is consistent with the aims of the new medical curricula. PMID- 11758619 TI - The Bristol Royal Infirmary Inquiry 18th July 2001. PMID- 11758620 TI - TDs support childhood immunisation. PMID- 11758621 TI - The mental health of migrants. PMID- 11758622 TI - Giant adrenal myelolipoma presenting with spontaneous hemorrhage. CT, MR and pathology correlation. AB - We report a case of a 56-year old symptomatic patient found to have a giant adrenal myelolipoma with hemorrhage. The characteristic CT and MR features and their aid in the diagnosis are demonstrated. We propose a definition of the often quoted term "giant" adrenal myelolipoma. PMID- 11758623 TI - Autonomy vs welfare? Anatomy of a risky discharge. AB - Questions about competence are often encountered when considering whether an elderly person with disability or cognitive impairment should return to their own home. This paper discusses the issues raised by one such case. It is argued that autonomy is a good in itself, whether or not it advances welfare. Hence, unless incompetence is clearcut, patients who wish to go home must go home, regardless of whether or not health care professionals view this as the best or safest choice. PMID- 11758624 TI - Metastatic melanoma of the tonsil. PMID- 11758625 TI - The extent of unlicensed and off-label drug use in the paediatric ward of a district general hospital in Northern Ireland. AB - Children receive many drugs which are either unlicensed or used outside the licensing terms (off-label prescribing). Children are thereby at greater risk of side-effects. We sought to determine non-licensed drug usage in a non-specialised paediatric unit because previous studies had examined only specialised centres. Drug charts were examined prospectively over two months. Items were compared with product licenses and determined as licensed, unlicensed or off-label usage. Seventy four charts (237 prescriptions) were examined in which 183 (77.2%) drug courses were licensed. The commonest drugs were antipyretics and antibiotics. In 32 children, 8 items (3.4%) were unlicensed and 46 items (19.4%) were off-label prescriptions. The unlicensed prescriptions were mostly anti-emetics and pro motility drugs. The three commonest off-label prescriptions were bronchodilators, antibiotics and laxatives. Non-licensed drug usage is common in non-specialised wards and therefore probably all levels of paediatric healthcare provision. Governments must re-examine paediatric drug licensing. PMID- 11758626 TI - The North Dublin Diabetes Shared Care (DiSC) Project: a profile of current diabetes care in Ireland. AB - The DiSC Project aims to assess the feasibility, effectiveness and costs of diabetes shared care in Ireland. Baseline results provide a profile of diabetes care in Ireland. Thirty general practices are participating in this randomised controlled trial. Outcomes include biophysical and psychosocial measures. The majority of patients agreed to participate in diabetes shared care. Data was collected from 183 patients with type 2 diabetes. The mean age of the patients is 65 years, 56% are male and 63% are GMS eligible. The mean HBA1c was 6.8% though 21% of patients had a HBA1c>8%. The majority of patients had a blood pressure, total cholesterol and body mass index above recommended guidelines. Only half the patients are attending a dietician or a chiropodist. The majority of patients have good glycaemic control but poor blood pressure and cholesterol control. The full trial results will determine if a shared care approach can improve clinical and psychosocial outcomes for patients. PMID- 11758627 TI - Minor salivary glands: causing major problems. AB - Tumours arising in the parapharyngeal space (PPS) are rare and account for approximately 0.5% of all head and neck neoplasms. These neoplastic processes represent a wide variety of both benign (80%) and malignant lesions arising from the diverse range of structures within and surrounding the PPS. The PPS is typically conceptualized as a potential neck space in the shape of an inverted cone with its base at the skull base and apex at the greater cornu of the hyoid. Because of this unique structure, lesions must often grow to a considerable size before symptoms become apparent and clinical detection is possible. A rare case of mucoepidermoid tumour of the minor salivary glands arising in the prestyloid parapharyngeal space is described. The complex anatomical and pathological considerations within this region present a substantial challenge to the head and neck surgeon in the evaluation and management of these lesions. PMID- 11758629 TI - Maternal admissions to ICU--time to re-evaluate. PMID- 11758628 TI - A measurement of the efficacy of anticoagulation monitoring in a general practice based setting. AB - With increasing numbers of patients on anticoagulant therapy and a trend towards moving certain hospital services to a primary care setting, we looked at how GPs are managing Warfarin therapy in their patients. This prospective study measured the efficacy of INR monitoring in 325 patients who were being managed in a general practice setting. 41% (415 of 1016) of readings fell strictly within the target ranges recommended by the British Society for Haematology. There was a low rate of haemorrhagic events (3.7%) in patients on Warfarin. Possible methods of improving readings include the introduction of Decision Support Services and formal training. PMID- 11758630 TI - An unusual presentation of appendicitis. PMID- 11758631 TI - Tuberculosis of the parotid gland in a patient with otorrhoea. PMID- 11758632 TI - Re: Giant cell arteritis--Jan 01 Vol 94 No 1. PMID- 11758633 TI - Checklist for autism in toddlers. PMID- 11758634 TI - Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. AB - BACKGROUND: Pharmacodynamic models of acetaminophen analgesia in children have not explored the efficacy of single oral doses greater than 40 mg/kg. METHODS: Children aged 9.0 +/- 3.0 years (+/- SD) and weight 37.9+/- 16.6 kg undergoing outpatient tonsillectomy were randomised to receive acetaminophen elixir 40 mg/kg (n = 12). high dose acetaminophen elixir 100 mg/kg (n =20) or placebo (n=30) 0.5 1 h preoperatively. No other analgesics were given. Individual acetaminophen serum concentrations and pain scores [visual analogue scale (VAS) 0-10] were measured over a 4-8 h postoperative period. These data were pooled with data from a previous study investigating acetaminophen pharmacodynamics (n = 120) and analysed using a non-linear mixed effect model. Placebo effects and drug effects were modelled using effect-site concentration models. RESULTS: A one-compartment model with first-order input, lag time and first-order elimination was used to describe the population pharmacokinetics of acetaminophen. Pharmacokinetic parameter estimates were similar to those previously described. Pharmacodynamic population parameter estimates [population variability coefficient of variation (CV)] for a maximum analgesic effect (Emax) model, in which the greatest possible pain relief (VAS 0-10) equates to an Emax of 10, were Emax 5.17 (64%) and 50% effective concentration 9.98 mg/l (107%). The equilibration half-life (t(eq)) of the analgesic effect compartment was 53 min (217%). A placebo drug model for the effects of placebo response had a t(eq) of 1.96 h (40%), an elimination half-life of 2.06 h (50%) and a potency of 1.54 pain relief units (24%). CONCLUSIONS: High dose acetaminophen (100 mg/kg) was no more effective than 40 mg/kg and was associated with increased nausea and vomiting. A target effect compartment concentration of 10 mg/l is expected to produce a pain reduction of 2.6 units. The placebo model accounted for a maximum pain reduction of 5.6 units at 3 h. The combination of placebo effect and preoperative acetaminophen 40 mg/kg results in pain scores below 4 units for 5 h postoperatively. PMID- 11758635 TI - Absorption, distribution, metabolism and excretion of [14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. AB - The main goal of the present study was to investigate the absorption and disposition of levocetirizine dihydrochloride, the R enantiomer of cetirizine dihydrochloride, following a single oral administration (5 mg) of the 14C labelled compound in healthy volunteers. Configurational stability was also investigated. Levocetirizine was rapidly and extensively absorbed: 85.4% and 12.9% of the radioactive dose were recovered 168 h post-dose in urine and faeces, respectively. Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68. The mean apparent volume of distribution (Vz/F) was 26.9 1 (0.3 l/kg) indicating that the distribution of levocetirizine is restrictive. The protein binding of radiolabelled levocetirizine was 96.1% l h after administration. In vitro, at concentrations ranging from 0.2 microg/ml to 1 microg/ml, the protein binding was 94.8% to 95.0%. Levocetirizine is very poorly metabolised. The cumulative 48-h excretion as parent compound accounted for 85.8% of the oral dose, equivalent to 95% of the total radioactivity excreted at this time. At least 13 minor metabolites were detected in urine and represented 2.4% of the dose at 48 h. The metabolic pathways involved in levocetirizine metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. There was no evidence of chiral inversion of levocetirizine in humans. This result is consistent with that obtained in preclinical studies. PMID- 11758636 TI - Enantioselective binding of disopyramide to alpha1-acid glycoprotein and its variants. AB - OBJECTIVE: alpha1-acid glycoprotein (AAG) has three main genetic variants, F1, S, and A variants. There are few reports on the correlation between AAG variants and binding activity of drug enantiomers. We studied the differences between the binding characteristics of enantiomers of disopyramide (DP), which is a basic drug. The aim of this study was to elucidate the cause of the differences between the binding characteristics of DP enantiomers. METHODS: The variants in human AAG were separated by hydroxyapatite chromatography. Binding of DP enantiomers to AAG variants was studied by the ultrafiltration method. The characteristics of the binding of DP enantiomers to total variants and each variant were examined by Scatchard analysis within a range of concentrations from 0.5 to 50.0 microg/ml. RESULTS: The binding capacity of S-DP was significantly higher than that of R-DP in variant 3, although the binding capacities of DP enantiomers were almost the same in variant 2. On the other hand, the binding capacities for both S-DP and R DP in variant 3 were significantly higher than those in variant 2. Furthermore, there was an almost 2.4-fold difference in the dissociation constant (Kd) between S-DP and R-DP in variant 3, although no significant difference was observed in the number of binding sites (N). In variant 2 no significant differences between DP enantiomers were observed in either the dissociation constant or number of binding sites per molecule of AAG. On the other hand, significant differences between variants 2 and 3 in the dissociation constant for both S-DP and R-DP were observed. The differences in dissociation constant between variants 2 and 3 were 4.0-fold in S-DP and 1.7-fold in R-DP. CONCLUSION: The difference between the binding capacities of S-DP and R-DP is due to differences in the association of DP to variants 3-6, and the role of the variants 1 and 2 in the binding of drugs to AAG is minor. PMID- 11758637 TI - Is cognitive impairment a risk factor for poor compliance among Japanese elderly in the community? AB - OBJECTIVE: The association between cognitive impairment and compliance with prescribed medications was investigated among functionally independent Japanese elderly in the community. SUBJECTS: The subjects of this study were 220 elderly persons aged 60 years and over, who lived in the community. All participants were taking a regimen of one or more prescribed drugs. We included elderly with mild to moderate cognitive impairment. Medication use was observed by pharmacist conducted interviews during home visits. Compliance was estimated by the pill count method. The Mini-Mental State Examination (MMSE) was used to estimate cognitive function. RESULTS: The mean age (SD) of the subjects was 75.7 (6.9) years. Of the subjects, 58 (26.4%) were cognitively impaired (MMSE < or = 23), and 76 (34.6%) exhibited poor compliance (rate of compliance< 80%). Poor compliance was associated with the subjects who had a lower education level, had lower MMSE scores, had concern about taking drugs, who intentionally self selected (intentional noncompliance) prescribed drugs, had a poor relationship with a physician, who did not have one dose package, and those who did not use a medical calendar. In multiple logistic regression analyses, intentional noncompliance (OR 19.65, 95%, CI 9.22-41.92; OR, odds ratio; CI, confidence interval), cognitive impairment (MMSE < or = 23; OR 2.94, 95%, CI 1.32-6.58), and a poor relationship with a physician (OR 6.24. 95%, CI 1.55-25.20) were independent predictors of poor compliance for elderly in the community. CONCLUSION: We found that cognitive impairment was one of the predictors for poor compliance among the elderly who are functionally independent in the community. Intentional noncompliance was the strongest predictor for poor compliance, which was influenced by the relationship between patient and physician. Physicians should establish good communication with their elderly patients and provide some support to compensate for cognitive impairment. PMID- 11758638 TI - The prescription pattern of oral nitrates in coronary artery disease. Appropriateness and cost considerations. AB - OBJECTIVES: To evaluate the prescription patterns of oral nitrates in terms of appropriateness and cost in a community setting. METHODS: A period prevalence, descriptive, applied study. Data including age, gender, type of medication, dosage and cost were extracted from the database of the largest health maintenance organisation (HMO) in Israel. The study population included enrollees over 35 years of age who received oral nitrates at least once during the 12-month study period. RESULTS: Oral nitrates were prescribed for 8007 patients (mean age 72.85+/-9.59 years, male:female ratio 1:1). A total of 52,694 prescriptions were issued for 56,553 medications, of these 88.1% for mononitrates, which constituted 95% of the annual cost for patients and the HMO. The mean prescribed daily dose for the various drugs ranged from 30% less than to 50% more than the recommended dose. Combination therapy with at least two nitrates, which is not the recommended treatment, was given to 5% of the patients. The recommended alternative treatment will alleviate the financial burden for providers and patients. CONCLUSIONS: Improved prescription habits can provide enhanced quality as well as cost savings for patients and providers. PMID- 11758639 TI - Treatment of osteoporosis among older adults discharged from hospital in Italy. AB - OBJECTIVE: Osteoporosis and its complications represent one of the most important causes of morbidity and mortality among the elderly. Despite the availability of several drugs deemed effective at reducing the incidence of fractures, only a minority of patients receive pharmacological treatment. We studied patients with a diagnosis of osteoporosis at discharge from hospital in Italy to identify predictors of receiving specific pharmacological treatment and to analyse how the pattern of drug prescription has changed in the last decade. METHODS: We analysed data from a multicentre pharmacoepidemiology study that collected data on hospitalised patients throughout Italy. Patients with a diagnosis of osteoporosis admitted during five different surveys in 1988, 1991, 1993, 1995 and 1997 were considered for the present study. RESULTS: Of 863 patients with a diagnosis of osteoporosis, 461 (53.4%) received treatment. Age [odds ratio (OR) 0.86 for each decade of increment, 95% confidence interval (CI) 0.73, 0.99], male gender (OR 0.67, 95% CI 0.44, 0.99), number of comorbid conditions (4-5 vs. 0-3 conditions: OR 0.66, 95% CI 0.47, 0.91; 6 or more vs. 0-3 conditions: OR 0.47, 95% CI 0.31, 0.72) and number of medications (OR 0.92 for each drug increase, 95% CI 0.85, 0.99) were all associated with a reduced likelihood of receiving pharmacological treatment for osteoporosis. In contrast, concomitant corticosteroid use (OR 2.00, 95% CI 1.05, 3.80), admission for hip or vertebral fracture (OR 2.10, 95% Cl 1.12, 3.93) and year of survey (OR 1.11, 95% CI 1.01, 1.24) were independent predictors of a higher treatment rate. Among individual drugs, calcitonin use remarkably declined from 42.1% in 1988 to 0.8% in 1997 (P for trend <0.001), while bisphosphonate prescriptions increased from 1.3% in 1988 to 34.9% in 1997 (P for trend <0.001). Prescription of calcium did not change significantly throughout the decade examined, while vitamin D had a twofold increase (14.2% in 1988 to 26.2% in 1997, P for trend <0.001). CONCLUSIONS: Among patients discharged from hospital in Italy, osteoporosis is an uncommon diagnosis. Even when the diagnosis is made, osteoporosis is often undertreated, and treatment is reserved for younger and less medically complex patients. PMID- 11758640 TI - Antidepressant drug prescribing in Italy, 2000: analysis of a general practice database. AB - OBJECTIVE: Databases of subjects receiving antidepressants provide evidence on the use of drugs in typical patients and settings under real-world conditions. This study analysed a general practice database to estimate the prevalence of antidepressant drug use, describe the use of these compounds by gender and age and estimate the prevalence of occasional versus non-occasional users. METHODS: The general practice database of Chivasso, a city near Turin in Piedmont, was analysed. The database includes all community (i.e. outside hospitals) prescriptions reimbursed by the National Health System in the population living in the study area. From the database, the total number of units of antidepressant drugs prescribed over a 6-month period was extracted. Using the general practice patient code, all records were converted into a sample of patients receiving one or more prescriptions of one or more antidepressants. RESULTS: During the 6 months surveyed, 12,930 antidepressant prescriptions were dispensed to 3751 patients, resulting in a prevalence of use of 19 patients per 1000 inhabitants (confidence interval 18.3, 19.5). The prevalence of use progressively increased with age and was more than double in females than males (female/male ratio 2.16). Paroxetine was the most prescribed compound, followed by amitriptyline and fluoxetine. However, in older subjects, the top two antidepressants were trazodone and amitriptyline. Nearly one-fourth of all dispensed antidepressants were prescribed on one occasion only; occasional users were slightly younger than non-occasional users. CONCLUSIONS: In Italy, databases have been used to monitor the prescription of medicines, but they have always provided aggregate data on drug sales and consumption. In this study, a sample of typical patients receiving antidepressants under real-world conditions was analysed to help clarify what happens in clinical practice. Databases of patients receiving antidepressants should be adopted to suggest public health priorities and generate original research hypotheses to be formally tested with experimental studies. PMID- 11758641 TI - Drug prescribing in out-patient children in Southern Italy. AB - OBJECTIVES: The aim of this study was to investigate and evaluate the prescribing habits of family pediatricians in Southern Italy in order to determine which aspects need to be addressed for a more rational use of drugs in children. METHODS: An observational prospective study was conducted for a 3-month period in 1998 in which family pediatricians were asked to record information regarding every patient doctor contact on an index day of the week. The information was collected on a specifically designed data collection form and included the reason for the contact, the child's general characteristics, the drugs prescribed, and the purpose for which they were prescribed (therapeutic indication). The data were entered, prescribed drugs were classified according to the International Anatomic-Therapeutic-Chemical Classification system (ATC), and the therapeutic indications were coded using the International Classification of Diseases (ICD 9). Analyses were carried out using the EPI-Info software package and the SPSS statistical analysis program. RESULTS: A total of 35 pediatricians participated and consulted with 9917 children, prescribing 8805 drugs to 6417 patients under 12 years old. Prescription rates were higher for younger children. In all, 288 different generic substances were prescribed, but the 20 most common made up two thirds of the prescriptions and would have sufficed to cover almost 70% of all prescription purposes. Two-thirds of prescriptions concerned respiratory system drugs or anti-infectives. Acute pharyngotonsillitis, cough, and acute otitis media were the most common morbidities. Despite the free availability of drugs in the Italian health care system, the families paid for over half their cost mainly due to the incorrect manner in which they were prescribed. CONCLUSIONS: Although, according to current recommendations, most of the patients' needs could have been taken care of using few drugs, prescriptions involved a wide variety of compounds. Prescription practices did not follow guidelines and were widely "evidence unbased". Prescribing drugs is one of the most frequent interventions in general practice, yet more effort is needed to establish a rational use of drugs in children, as well as in adults. PMID- 11758642 TI - Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia. PMID- 11758643 TI - State-specific cholesterol screening trends--United States, 1991-1999. AB - High blood cholesterol (HBC) increases the risk for heart disease, the leading cause of death in the United States. To reduce the prevalence of HBC in the United States, the National Heart, Lung, and Blood Institute initiated the National Cholesterol Education Program in 1985 and recommended that all adults aged > or =20 years have their cholesterol levels checked at least once every 5 years. One of the national health objectives for 2000 was to increase to 75% the proportion of adults aged > or =20 years screened for HBC during the preceding 5 years (objective 15.14). This objective was revised for 2010 to recommend that 80% of adults in this age group be screened during the preceding 5 years. To monitor progress during the 1990s and to determine whether the 2000 objective was attained, data from CDC's Behavioral Risk Factor Surveillance System (BRFSS) were used to examine the state-specific trends in cholesterol screening from 1991 through 1999. This report summarizes the results of this analysis and provides a projected estimate of the 2010 screening rates for HBC in each state. The findings indicate that few states attained the 2000 objective and that more emphasis on cholesterol screening will be needed to attain the 2010 objective. PMID- 11758644 TI - Trends in cigarette smoking among high school students--United States, 1991-1999. AB - One of the 10 Leading Health Indicators that reflect the major health concerns in the United States is cigarette smoking among adolescents. To examine changes in cigarette smoking among high school students in the United States from 1991 to 1999, CDC analyzed data from the national Youth Risk Behavior Survey (YRBS). This report summarizes the results of the analysis and indicates that current smoking among U.S. high school students increased significantly from 27.5% in 1991 to 34.8% in 1999; however, the analysis also suggested that, later in the decade, current smoking may have leveled or possibly begun to decline. PMID- 11758645 TI - Progress toward poliomyelitis eradication--Pakistan, 1999-June 2000. AB - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by the end of 2000. Although polio remains endemic in Pakistan, which reported 60% of all polio cases in the World Health Organization's (WHO) Eastern Mediterranean Region during 1999, substantial progress has been made, particularly in acute flaccid paralysis (AFP) surveillance. This report summarizes progress toward polio eradication in Pakistan. PMID- 11758646 TI - Effects of DNA vaccine in murine malaria using a full-length cDNA library. AB - In an attempt to develop a novel malaria vaccine, we constructed a full-length cDNA library from the erythrocytic-stage parasites of Plasmodium berghei ANKA strain using the plasmid vector pCE-FL, which is driven by an EF321 promoter and a CMV-IE enhancer. Here we report the initial trial to screen this library for DNA vaccine candidates against malaria parasite infection in mice. The library of P. berghei was divided into five groups, each representing 2,000 independent clones. Eight female BALB/c mice were injected with these subsets, with an initial injection directly into the spleen, followed by two subsequent intramuscular injections at 1-week intervals. As a control, the plasmid vector without any insert was used. Two weeks after the last injection, 50,000 infected erythrocytes were injected intraperitoneally. Unexpectedly, the survival rate of the vaccinated groups was lower than that of the control (p = 0.053, by Kaplan Meyer method), suggesting that these DNA vaccines had adverse effects. There was no difference in parasitemia between the two groups. There was no difference between antibody titers before and after immunization in either group. Accelerated deaths in immunized mice occurred from 7 to 10 days after infection, when fur bristling, shivering and convulsions were observed. These observations suggested the possibility that the vaccination had an adverse effect on the cellular immunity that resulted in the development of severe malaria in BALB/c mice, which do not usually develop cerebral malaria. PMID- 11758647 TI - Plasma type II phospholipase A2 levels in patients with acute pancreatitis. AB - Changes in the blood levels of type II phospholipase A2 (PLA2) were investigated over time in patients with acute pancreatitis from an early stage after manifestation of the disease. The serum level of type II PLA2 at the first examination and the maximum level during the course of illness were both correlated with the severity of the disease. Serum levels of type II PLA2 were significantly higher in patients with acute pancreatitis complicated by multiple organ failure (349.1 +/- 146.6 ng/ml) than in those with acute pancreatitis not complicated by multiple organ failure (66.9 +/- 50.1 ng/ml). The serum levels of type II PLA2 were also significantly higher in patients who eventually died (316.8 +/- 150.5 ng/ml) than in those who survived (148.9 +/- 167.9 ng/ml). There was a significant correlation between the serum levels of type II PLA2 and those of TNF-alpha during the course of illness (r = 0.8037, p < 0.0001). The serum levels of type II PLA2 reliably reflected the severity of acute pancreatitis even in the early stages of the disease. These results suggest that type II PLA2 may be closely involved in the pathophysiology of acute pancreatitis. PMID- 11758648 TI - Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract. AB - Grape seed proanthocyanidins are known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. Previous studies in our laboratories have demonstrated the various protective abilities of a novel IH636 grape seed proanthocyanidin extract (GSPE) against various pathologic conditions. However no extensive safety studies have been conducted on grape seed proanthocyanidins to date. This study demonstrates the acute and chronic safety studies on GSPE. Acute oral toxicity, dermal toxicity, dermal irritation and eye irritation studies have been conducted. The LD50 of GSPE was found to be greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female albino rats. The LD50 of GSPE was found to be greater than 2000 mg/kg when administered once for 24 hr to the clipped, intact skin of male and female albino rats. In addition, 2000 mg/kg was found to be the no-observed effect level (NOEL) for systemic toxicity under the conditions of the study. In a dermal irritation study, GSPE received a descriptive rating classification of moderately irritating. Extensive chronic studies were also conducted. We have assessed the effects of chronic administration of 100 mg GSPE/kg/day for twelve months and its effect on seven vital target organs, namely, brain, heart, intestine, kidney, liver, lung and spleen, and on serum chemistry changes in male B6C3F1 mice. Furthermore, the dose-dependent chronic effects of GSPE in female B6C3F1 mice were evaluated. Mice were fed 0, 100, 250 or 500 mg GSPE/kg/day for six months and the effects of GSPE exposure were examined on brain, duodenum, heart, kidney, liver, lung, pancreas and spleen, and on serum chemistry changes in female mice. These acute studies demonstrated that GSPE is safe and did not cause any detrimental effects in vivo under the conditions investigated in this study. PMID- 11758649 TI - The perfused guinea-pig lung revisited: a study of EDRF-no system. AB - Adult male guinea pigs from both sexes were anaesthetized with pentobarbital (40mg/Kg). After tracheotomy the lungs were perfused with Krebs-Henseleit solution at 37 degrees C in a non recirculated system composed of a perfusion pump, a transducer to measure pressure and another one to measure bronchial resistance. In all groups studied histamine injections were made at the doses of 50, 100, 200 and 400 microg/ml as a bolus. Propranolol (1 microg/ml) added to the perfusate, promoted a remarkable increase in perfusion pressure (p<0.001) and a significant augmentation in bronchoconstriction (p<0.05). When indometacin (10 microg/ml) was added to the perfusate, a great increase in histamine induced bronchoconstriction was observed, that was followed by a remarkable increase in perfusion pressure. Methylene blue at the dose of 8.25 microg/ml increased bronchorreativity as well as the perfusion pressure significantly. L-arginine (3.5 microg/ml) added to the perfusate, did not promote reactivity. The addition of L-arginine plus NADPH (1 microg/ml), promoted a significant decrease in bronchoconstriction (p<0.01). In both cases, perfusion pressure increased when compared to controls. Nitroarginine (2.5 microg/ml) greatly increased perfusion pressure with no change in bronchoconstriction. Therefore, we conclude that nitric oxide (NO) is a very important modulator for keeping the low perfusion pressure and bronchodilation of the isolated perfused guinea pig lung. PMID- 11758650 TI - Effect of hydroxycitric acid on serotonin release from isolated rat brain cortex. AB - There is evidence that hydroxycitric acid (HCA), an extract of dried fruit rind of South Asian trees of the genus Garcinia cambogia, can reduce food intake in experimental animals. In the present study, we investigated the effect of HCA on basal and potassium-depolarization evoked increase in radiolabeled serotonin ([3H]-5-HT) release from rat brain cortex slices in vitro. HCA (10 microM-1 mM) altered the baseline of spontaneous tritium efflux but had no significant effect on potassium-evoked release of [3H]-5-HT. When applied on its own, HCA (10 microM 1 mM) elicited a concentration-dependent increase in efflux of [3H]-5-HT reaching a maximum at 300 microM. We conclude that HCA can increase the release of radiolabeled 5-HT from the isolated rat brain cortex. PMID- 11758651 TI - 5-Hydroxytryptamine (5-HT)-induced depolarization in isolated abdominal vagus nerves in the rat: involvement of 5-HT3 and 5-HT4 receptors. AB - In this study, we developed an electrophysiological technique for the in vitro measurement of isolated abdominal vagus nerve depolarization in the rat. This technique was used to compare abdominal and cervical vagus nerve depolarization values. Both 5-HT and a selective 5-HT3 agonist, 2-CH3-5HT, caused a concentration-dependent depolarization in rat isolated abdominal vagus nerves in vitro. Isolated cervical vagus nerves also showed concentration-dependent depolarization, although the isolated cervical vagus nerve depolarization was approximately 60% of that of the isolated abdominal vagus nerves at similar concentration ranges of 5-HT and 2-CH3-5HT in vitro. In isolated abdominal vagus nerves, a selective 5-HT3 antagonist, granisetron, produced a concentration dependent decrease, but reduced the maximal response of 5-HT-induced depolarization in vitro. In isolated abdominal vagus nerves, selective 5-HT4 antagonist, SB204070, produced parallel and concentration-dependent shifts to the right on the concentration-response curves to 5-HT in vitro. These findings suggest that this electrophysiological method for evaluating isolated abdominal vagus nerve depolarization is a useful technique for the estimation of 5-HT induced depolarization. PMID- 11758652 TI - Estimation of absorption enhancement by medium-chain fatty acids in rat large intestine. AB - The absorption enhancement by the sodium salts of several fatty acids was investigated in rat large intestine for model compounds having a wide range of molecular weight. Sodium caprylate (C8), sodium caprate (C10), sodium laurate (C12), which are categorized in medium-chain fatty acid, and sodium oleate (C18:1), long-chain unsaturated fatty acid, were employed as lipoidal adjuvants. Phenol red (MW=354.4), glycyrrhizin (822.9), fluorescein isothiocyanate-dextran-4 (FD-4, 4400), FD-10 (9400) and FD-40 (38900) were selected as model compounds for the assessment of the enhancing effect of the lipoidal adjuvants. The absorption of phenol red was promoted at the highest level, about 20 times higher by C12 and C18:1 than the control. The absorption rate - time profiles calculated by deconvolution method showed that C12 takes effect most rapidly and efficiently. In the case of glycyrrhizin, four adjuvants including C12 showed almost the same improvement of the absorption, about 30-40 times larger than the control. C8 and sodium citrate did not significantly enhance the absorption of those model compounds. For FD-4, FD-10 and FD-40, C10, C12 and C18:1 revealed almost the same enhancing effect and the absorption of FD-4, FD-10 and FD-40 was enhanced about 80 times, 1000-1800 times and about 200 times, respectively, larger than the control. The enhancement ratio, the ratio of AUC with adjuvant to AUC of control, suggests that these lipoidal adjuvants would improve most efficiently the absorption of the compound having the molecular weight of around 10000. Furthermore, C12 was suggested to be an effective adjuvant for the compounds with the wide range of molecular weight. PMID- 11758653 TI - A new immunological marker of atherosclerotic injury of arterial wall. AB - BACKGROUND AND OBJECTIVE: The atherosclerotic arterial injuries lead to many life threatening vascular incidents. It has been well documented that inflammatory processes play an important role in atherogenesis. Intensive studies are undertaken to find a serum marker of inflammatory reaction correlated with arterial injuries. METHODS: In our study we measured the level of interleukin-6 (IL-6) in patients with dyslipidemia IIa and IIb biochemically confirmed. Control estimations were done in age-matched group. Arterial injuries were evaluated as a thickening of complex intima-media in common carotid arteries by means of Doppler ultrasonography. RESULTS: Levels of IL-6 were significantly higher in both groups of patients with dyslipidemia as compared with the healthy control persons (IIa vs control p<0.001, IIb vs control p<0.001). The plasma level of IL-6 is significantly correlated to intima-media complex thickness (r=0.68, p<0.0001). CONCLUSION: We conclude that increase of serum concentration of IL-6 may be related to arterial wall injuries in the course of the most atherogenic lipid disorders. PMID- 11758654 TI - High-performance liquid chromatographic analysis of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378. AB - A high-performance liquid chromatographic method was developed for the determination of a neuroprotective agent for ischemia-reperfusion damage, KR 31378, in human plasma and urine and in rat tissue homogenates. The method involved deproteinization of the the biological samples with 0.5 volumes of saturated Ba(OH)2, 0.5 volumes of 0.04 M ZnSO4 and 1 volume of acetonitrile. A 80 microl aliqout of the supernatant was injected onto a reversed-phase C18 column. The mobile phase, 50 mM triethylamine acetate : acetonitrile : tetrahydrofuran (65:30:5, v/v/v), was run at a flow rate of 1.0 ml/min. The column effluent was mornitored by a ultraviolet detector set at 310 nm. The retention time of KR 31378 was approximately 6.5 min. The detection limits of KR-31378 in human plasma and urine and rat tissue homogenates were 0.2, 0.5 and 0.5 microg/ml, respectively. The coefficients of variation (within-day and between-day) were below 13.6% for human plasma and urine and rat homogenates. No interferences from endogenous substances were found. PMID- 11758655 TI - Anhedonia in depression and schizophrenia: a reexamination. AB - The purpose of this study was to utilize factor analysis to help determine whether anhedonia is a symptom of both depression and schizophrenia. Measures of depression, positive and negative symptoms of schizophrenia, and anhedonia were administered to a group of schizophrenic patients (N = 54) and to a group of patients with major depressive disorder (N = 27). The correlation matrix among the various scales was subjected to an oblique exploratory factor analysis. Three factors were extracted, accounting for three quarters of the variance. The first measured depression, the second measured positive symptoms, and the third measured negative symptoms. Anhedonia loaded significantly on the first factor but not on the third, suggesting that it is a symptom of depression rather than schizophrenia. These results were corroborated by means of confirmatory factor analysis. We conclude that anhedonia is a symptom of depression and that it only appears to be a symptom of schizophrenia because it is a component of emotional blunting which is indeed a negative symptom of schizophrenia. PMID- 11758656 TI - The incidence of schizotypy among cannabis and alcohol users. AB - Schizotypy research has revealed associations between positive schizotypal symptomatology and substance use but has not related substance use to important schizotypal traits such as anhedonia. Users and nonusers of cannabis and alcohol completed the Oxford-Liverpool Inventory of Feelings and Experiences, the Peters Delusion Inventory, and the Hospital Anxiety and Depression Scale. Cannabis users scored significantly higher on Unusual Experiences, a scale measuring positive schizotypal symptomatology. Both cannabis and alcohol usage were associated with significantly lower scores on Introvertive Anhedonia, which represents negative symptomatology. Delusional ideation and delusional conviction were significantly higher in cannabis users, but for delusional conviction this was only true for users who also drank alcohol. Neither anxiety or depression scores were higher in cannabis users, but delusional ideation correlated with both anxiety and depression, thus providing mixed support for the idea of the "happy schizotype." Overall, these results suggest that cannabis and alcohol usage is related to different dimensions of psychosis-proneness that broadly parallel the relationship between substance use and positive and negative schizophrenic symptoms, thus supporting the continuity view of psychosis and the multidimensionality of psychosis-proneness. PMID- 11758657 TI - The preschizophrenic character, 1913. PMID- 11758658 TI - Cognitive slippage in schizotypic individuals. AB - The Miers and Raulin Cognitive Slippage Scale was used to assess subtle thought disorder, and the Wisconsin Card Sorting Test (WCST) was used to assess cognitive performance in deviantly high scorers on the Perceptual Aberration and Magical Ideation Scales (N = 63), high scorers on the revised Social Anhedonia Scale (N = 62), and in control subjects (N = 83). Results indicate that schizotypic individuals are more likely to report greater cognitive slippage and less likely to achieve as many WCST categories as controls. Individuals with both positive and negative symptoms of schizotypy reported higher levels of cognitive slippage than those individuals reporting only negative schizotypy. Additionally, the results confirm the presence of an especially high-risk group of psychosis-prone individuals, namely, those individuals with deviant scores on the revised Social Anhedonia Scale who possess additional indicators of schizotypy. PMID- 11758659 TI - Visual exploration of emotion eliciting images by patients with schizophrenia. AB - To examine the relationship between emotional activation and information gathering in schizophrenia, the eye movements and emotional responses of 20 patients with schizophrenia and 10 patients without history of psychosis were recorded while viewing 30 images varying in pleasantness. Emotionally activating pictures were more extensively explored than neutral pictures by both groups but especially by schizophrenia patients. Comparison patients explored pictures more extensively during the early part of image exposure, whereas patients with schizophrenia took longer to engage in informative exploration. The scan path lengths and the proportions of fixation time spent in regions of interest did not differ between groups, although persons with schizophrenia had longer fixations and looked at fewer regions of interest in neutral pictures. Emotion reports did not differ between groups. Schizophrenia patients' results are consistent with the hypothesized normalizing effects of emotional activation on the distribution of attention. PMID- 11758660 TI - Impact of clozapine prescription on inpatient resource utilization. AB - Although clozapine has been demonstrated to be clinically superior to typical neuroleptics in refractory schizophrenia, it is also more expensive. It had been hoped that the increased costs associated with its use would be offset by decreases in the utilization of other expensive resources, especially inpatient care. All patients who had clozapine initiated during an inpatient hospitalization within the VA for schizophrenia over a 4-year period (N = 1415) were matched with a comparison group (N = 2,830) on key service utilization variables and other possible confounding demographic and clinical variables using propensity scoring-an accepted statistical method, although still relatively little used in psychiatry. By using centralized VA databases, subsequent inpatient resource utilization for the 3 years after index discharge was examined. Veterans exposed to clozapine while inpatients recorded 33 (36%) more inpatient days in the subsequent 3 years after discharge than the comparison group (124 +/- 190 days vs. 91 +/- 181 days, p = .0002). When all patients exposed to clozapine were divided according to whether they had received 1 year of clozapine treatment after discharge, those that received less than 1 year's treatment recorded significantly more inpatient days than either those maintained on clozapine or controls. These results suggest that in actual practice clozapine treatment may cost substantially more than treatment with conventional neuroleptics. PMID- 11758661 TI - Cognitive treatment of pathological gambling. AB - This study evaluated the efficacy of a cognitive treatment package for pathological gambling. Sixty-six gamblers, meeting DSM-IV criteria for pathological gambling, were randomly assigned to treatment or wait-list control conditions. Cognitive correction techniques were used first to target gamblers' erroneous perceptions about randomness and then to address issues of relapse prevention. The dependent measures used were the South Oaks Gambling Screen, the number of DSM-IV criteria for pathological gambling met by participants, as well as gamblers' perception of control, frequency of gambling, perceived self efficacy, and desire to gamble. Posttest results indicated highly significant changes in the treatment group on all outcome measures, and analysis of data from 6- and 12-month follow-ups revealed maintenance of therapeutic gains. Recommendations for clinical interventions are discussed, focusing on the cognitive correction of erroneous perceptions toward the notion of randomness. PMID- 11758662 TI - Ambivalence and other relationship predictors of grief in psychiatric outpatients. AB - Ambivalence has been viewed as an important causal agent in the development of complicated grief. However, examination of studies commonly cited as supporting this belief reveals basic limitations in their methodology and conclusions. The current study examined associations between several relationship predictors (ambivalence, affiliation, and dependence) and both grief-specific symptoms and depression in two samples of psychiatric outpatients who had experienced loss of significant others. Findings from the first sample (N = 138) were used to test for evidence of cross-validation in the second sample (N = 139). Contrary to traditional belief, ambivalence was inversely related to severity of grief symptoms. In contrast, affiliation and dependence were directly related to severity of grief symptoms. None of the predictors provided evidence of cross validation in the case of depression. Explanations for the findings and clinical implications are considered. PMID- 11758663 TI - Temperament and character in italian men with anorexia nervosa: a controlled study with the temperament and character inventory. AB - This study compares personality traits of men and women with anorexia nervosa and matched controls. The Temperament and Character Inventory was used to assess personality traits of 15 male and 50 female anorectics and 28 male and 58 female controls matched for age and education. Male anorectic patients displayed overall lower reward dependence and cooperativeness. Male and female anorectics displayed higher persistence and lower self-directedness than controls. Anorectic men had lower harm avoidance than anorectic women. Discriminating analysis revealed the anorectic male group as the most clearly defined. Anorectic men shared more traits with anorectic women than with male controls. Temperament and character of anorectic men reflect features partly similar to those of women with anorexia. Personal history and discriminating analysis led to interesting inferences about the gender identity of anorectic men. These results should be helpful in directing pharmacologic and psychotherapeutic approaches that consider the specific personality traits of these patients. PMID- 11758664 TI - The diagnosis of posttraumatic stress disorder in Gulf veterans with medically unexplained fatiguing illness. PMID- 11758666 TI - Fluvoxamine and perphenazine for psychosis in Alzheimer's disease: pharmacokinetic considerations. PMID- 11758665 TI - Peritraumatic dissociation and posttraumatic stress disorder in victims of violent assault. PMID- 11758667 TI - Education, age, and the Brown-Peterson technique. AB - In this article, we discuss the effects of education level and age on short-term memory. The performance of young and elderly persons was compared on an adapted version of the Brown-Peterson procedure. Participants were asked to report consonant trigrams, after variable time periods, during which they performed a mental addition task or an articulation task. A control condition consisted of a no-interference task. Both age groups were divided according to individual educational level (greater or less than the median number of school years in each age group). The results revealed a significant effect of education. Moreover, the education effect interacted with the task: participants with less education were more impaired in mental addition than in articulation. However, neither the age effect nor the interactions involving age reached significance. These results indicate that education, to a greater extent than age, should be considered a determining factor of performance when interpolated tasks of high demand are used with the Brown-Peterson procedure. PMID- 11758668 TI - Callosal contribution to procedural learning in children. AB - A previous study in acallosal patients (De Guise, et al., 1999) has demonstrated the crucial role of the corpus callosum (CC) in a procedural learning task that requires the participation of both hemispheres. Because children often display limitations in interhemispheric communication linked to callosal immaturity, we expected that they would have difficulties learning a procedural skill that involved interhemispheric integration during its acquisition, but not when the skill was learned intrahemispherically. To test this hypothesis, 40 children, divided into 4 age groups (6 to 8 years, 9 to 11 years, 12 to 14 years, and 15 to 16 years), performed a modified version of the serial reaction time task developed by Nissen and Bullemer (1987). This task involves uni- or bimanual key pressing responses to a fixed sequence of 10 visual stimuli that are repeated 80 times. All the children were able to learn the visuomotor skill in the unimanual condition and to transfer it interhemispherically. However, only the older children (12 years and over) learned the task in the bimanual (interhemispheric) condition. The results indicate that the maturation of the CC affects interhemispheric acquisition of a procedural skill in two different ways: While the immature CC appears to be sufficient to transfer a skill acquired by one hemisphere, a mature CC seems to be required to learn the skill bihemispherically. The latter skill was achieved around the age of 12, coinciding with the end of the maturation cycle of the CC. Although the young children were unable to learn the bimanual task implicitly, some of them showed explicit knowledge of the procedure, confirming once again the dissociation between explicit and implicit memory suggested by Squire (1992). PMID- 11758669 TI - Executive functioning as a predictor of children's mathematics ability: inhibition, switching, and working memory. AB - Children's mathematical skills were considered in relation to executive functions. Using multiple measures--including the Wisconsin Card Sorting Task (WCST), dual-task performance, Stroop task, and counting span-it was found that mathematical ability was significantly correlated with all measures of executive functioning, with the exception of dual-task performance. Furthermore, regression analyses revealed that each executive function measure predicted unique variance in mathematics ability. These results are discussed in terms of a central executive with diverse functions (Shallice & Burgess, 1996) and with recent evidence from Miyake, et al. (2000) showing the unity and diversity among executive functions. It is proposed that the particular difficulties for children of lower mathematical ability are lack of inhibition and poor working memory, which result in problems with switching and evaluation of new strategies for dealing with a particular task. The practical and theoretical implications of these results are discussed, along with suggestions for task changes and longitudinal studies that would clarify theoretical and developmental issues related to executive functioning. PMID- 11758670 TI - Recording and analyzing high-density event-related potentials with infants. Using the Geodesic sensor net. AB - This article provides an overview of the use of the Geodesic sensor net system for high-density event-related potential (ERP) recording in infants. Some advantages and disadvantages of the system, as applied to infants, are discussed. First, we illustrate that high-density data can be recorded from infants at comparable quality to that observed with conventional (low density) ERP methods. Second, we discuss ways to utilize the greater spatial information available by applying source separation and localization procedures. In particular, we focus on the application of one recent source separation method, Independent Component Analysis (ICA). Finally, we show that source localization can be applied to infant high-density data, although this entails adopting a number of assumptions that remain to be verified. In the future, with improved source separation algorithms, we suggest that single-trial or single-subject analyses may become feasible. PMID- 11758671 TI - Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. AB - Gaucher disease is a typical lysosomal storage disease, resulting from an inborn deficiency of glucocerebrosidase. This leads to the accumulation of glycolipids in macrophages, particularly those in the liver, bone marrow, spleen and lung. In addition, disease of the nervous system can arise as a result of the accumulation of endogenous glycosphingolipid metabolites in brain tissue. About 150 mutations of the glucocerebrosidase gene have been identified in patients with Gaucher disease, some of which are predictive of phenotype. However, even patients and siblings with the same mutation, including monozygotic twins, may exhibit marked variability in disease expression and severity, illustrating our lack of understanding of the phenotype-genotype relationship in the sphingolipidoses. Massive organomegaly, particularly of the spleen, is a frequent feature of the disease. Although the liver and spleen may increase greatly in size, the amount of pathological lipid stored in the affected macrophages (Gaucher cells) accounts for less than 2% of the additional tissue mass. It is therefore clear that an inflammatory response occurs in affected individuals and that the clinical phenotype is due to an effect of macrophage storage beyond the physical presence of the Gaucher cells. Factors released by Gaucher cells, including pro inflammatory cytokines and perhaps cathepsins, provide a mechanistic link between lysosomal storage and the diverse clinical manifestations of Gaucher disease. Emerging proteomic technology and gene expression profiling should not only improve our understanding of pathogenesis but also offer the prospect of identifying novel biomarkers that can be used as surrogate measures of disease activity and responses to treatment. PMID- 11758672 TI - Remaining problems in the management of patients with Gaucher disease. AB - The history of treatment of Gaucher disease started with splenectomy and continued with bone marrow transplantation, before the recent introduction of enzyme replacement therapy. Although the latter has revolutionized the prognosis of patients, many questions remain to be answered and clinical management problems resolved. These include how to monitor enzyme replacement to determine the optimal dosage, how to treat mild disease, whether intermittent treatment is an option, and the causes of the neurological signs and how to treat them. The pulmonary hypertension problem has also not been resolved, and we need to determine how to treat and monitor bone disease. In addition, the future role of substrate deprivation needs to be determined, and further research is required before gene therapy becomes a potential clinical option. The high cost of enzyme replacement treatment for Gaucher disease remains an important issue. PMID- 11758673 TI - Natural history of Fabry disease in affected males and obligate carrier females. PMID- 11758674 TI - Natural history of Fabry disease in males: preliminary observations. AB - A large cohort of patients with Fabry disease is being studied to determine the natural history of the disease and how this relates to the specific mutation involved and the amount of residual alpha-galactosidase A activity. To date, we have investigated the progression of cerebral lesions and stroke, as identified by magnetic resonance imaging, and renal disease. Results have shown that cerebral lesions do not appear until 23 years of age, but are present in all patients by 55 years of age. The peak onset of proteinuria occurred in the fourth decade, and the peak onset of chronic renal insufficiency and end-stage renal disease occurred in the fifth decade of life. Renal outcome was related to the type of mutation and residual enzyme activity. Data from these studies in untreated patients will be important when assessing the long-term efficacy of enzyme replacement therapy. PMID- 11758675 TI - Enzyme replacement therapy in Fabry disease. AB - Recent clinical trials have demonstrated that enzyme replacement therapy with alpha-galactosidase A (alpha-Gal A) constitutes a major clinical advance in the treatment of patients with Fabry disease. This new therapeutic approach has been shown to be well tolerated and effective in reducing levels of the storage product globotriaosylceramide and in normalizing many of the debilitating manifestations of the disorder. A double-blind placebo-controlled trial in 26 hemizygous male patients showed that agalsidase alfa (human alpha-Gal A) significantly reduced neuropathic pain (p = 0.02), increased creatinine clearance (p = 0.02), improved glomerular histology, reduced the QRS interval on electrocardiography and increased weight gain. Positron emission tomography also revealed normalization of cerebrovascular flow. After the 6-month controlled period, all patients were given agalsidase alfa for a further 12 months. At the end of this period, all patients had a decrease in neuropathic pain, and there was a significant improvement in their ability to sense heat and cold. In addition, renal function stabilized, even in patients with renal insufficiency at the onset of treatment, and patients reported a normalization of sweating and improvements in their level of energy and sense of well-being. These findings show that enzyme replacement therapy offers promise as an effective management strategy for patients with Fabry disease. PMID- 11758677 TI - An historical overview of Fabry disease. PMID- 11758676 TI - Gene therapy for Fabry disease. AB - Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha galactosidase A (alpha-Gal A). Lack of this lysosomal hydrolase results in the accumulation of galactose-terminal glycosphingolipids in a number of tissues, including vascular endothelial cells. Premature death is predominantly associated with vascular conditions of the heart, kidneys and brain. Historically, treatment has largely been palliative. Alternative treatments for many lysosomal storage diseases have been developed, including allogeneic organ and bone marrow transplantation, enzyme replacement therapy, and gene therapy. Significant clinical risks still exist with allogeneic transplantations. Alpha-Gal A enzyme replacement therapy has been implemented in clinical trials. This approach has been effective but may have limitations for long-term systemic or cost-effective correction. As an alternative, gene therapy approaches, involving a variety of gene delivery systems, have been pursued for the amelioration of Fabry disease. Fabry disease is a compelling disorder for gene therapy, as target cells are readily accessible and relatively low levels of enzyme correction may suffice to reduce storage. Importantly, metabolic cooperativity effects are also manifested in Fabry disease, wherein corrected cells secrete alpha-Gal A that can correct bystander cells. In addition, a broad therapeutic window probably exists, and mouse models of Fabry disease have been generated to assist studies. As an example, in vitro and in vivo studies using alpha-Gal A-transduced haematopoietic cells from Fabry mice have demonstrated enzymatic correction of recipient cells and dissemination of alpha-Gal A upon transplantation, leading to reduced lipid storage in a number of clinically relevant organs. This corrective enzymatic effect has recently been shown to be even further enhanced upon pre-selection of therapeutically transduced cells prior to transplantation. This review will briefly detail current gene delivery methods and summarize results to date in the context of gene therapy for Fabry disease. PMID- 11758678 TI - Variable clinical presentation in lysosomal storage disorders. AB - Extensive clinical heterogeneity is seen in lysosomal storage disorders, regarding the age of onset and severity of symptoms, the organs involved, and effects on the central nervous system. A broad phenotypic spectrum is seen, for example, in mucopolysaccharidosis type I (Hurler/Scheie disease), Gaucher disease, the several forms of GM2-gangliosidosis and the different manifestations of beta-galactosidase deficiency (GM1-gangliosidosis and Morquio disease type B). Variable clinical expression of the same enzyme defect is not well understood. The presence of different mutations is only part of the explanation, as intrafamilial variability is observed in many cases. Other mechanisms, for example the effect of specific activators, may also have an influence on phenotype. PMID- 11758679 TI - Are there useful biochemical markers of disease activity in lysosomal storage diseases? AB - The primary biochemical consequence of a defect in a gene encoding a functional component of the lysosomal system is disruption of the catabolism or processing of macromolecules in the lumen of the lysosome. Transport of the resulting digestion products through the lysosomal membrane may also be affected. This leads to the accumulation of specific metabolites within the lysosomes of affected cells. The nature of these storage products depends upon the functional protein affected and the cell type. The accumulation of storage products is progressive and leads to hypertrophy of the lysosomal system, the hallmark of lysosomal storage diseases (LSDs). Subsequent cell necrosis or, possibly, exocytosis results in the appearance in body fluids of the storage products and components of the lysosomes at much higher concentrations than seen in normal unaffected individuals. Measurement of these increased levels of metabolites and proteins provides disease-specific and generic biochemical markers for LSDs. Secondary changes in metabolism and cellular function may also produce characteristic changes in the levels of metabolites or proteins, which can also be used as markers of the disease process. Although the rate of appearance of these biochemical markers in an individual will depend upon the underlying mutation in the gene and on other genetic and environmental factors, it provides a good indicator of the progression of the disease. As the novel forms of treatment being developed may reverse the hypertrophy of the lysosomal system, biochemical markers could also be used to monitor the reversal of pathology and the efficacy of treatment. PMID- 11758680 TI - Is genotype determination useful in predicting the clinical phenotype in lysosomal storage diseases? AB - Understanding the relationship between genotype and clinical phenotype will clearly aid in the prognosis, treatment and counselling of patients with lysosomal storage diseases (LSDs). This, however, will require the establishment of widely accepted indices with which to score the severity of LSDs, as these diseases are characterized by their marked clinical heterogeneity. Even in the complete absence of a functional enzyme, presentation may be variable, depending on the patient's genetic background and on a range of epigenetic and environmental factors. Further difficulties in predicting disease severity and progression from the genotype arise from the rarity of these disorders, the low enzyme levels required for a normal phenotype and the relative lack of understanding of the pathophysiology of LSDs. PMID- 11758681 TI - Renal pathological changes in Fabry disease. AB - Fabry disease is a rare X-linked disorder, characterized by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to systemic accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in all body tissues and organs, including the kidney. Renal manifestations are less evident in female heterozygotes than in male hemizygotes, according to the Lyon hypothesis. Accumulation of Gb3 occurs mainly in the epithelial cells of Henle's loop and distal tubule, inducing early impairment in renal concentrating ability; involvement of the proximal tubule induces Fanconi syndrome. All types of glomerular cells are involved, especially podocytes, and glomerular proteinuria may occur at a young age. The evolution of renal Fabry disease is characterized by progressive deterioration of renal function to end-stage renal failure (ESRF). Ultrastructural study of kidney biopsies reveals typical bodies in the cytoplasm of all types of renal cells, characterized by concentric lamellation of clear and dark layers with a periodicity of 35-50 A. Management of progressive renal disease requires dietetic and therapeutic strategies, usually indicated in developing chronic renal failure, with dialysis and renal transplantation required for patients with ESRF. The recent development of enzyme replacement therapy, however, should make it possible to prevent or reverse the progressive renal dysfunction associated with Fabry disease. PMID- 11758682 TI - Renal disease in Fabry patients. AB - Renal dysfunction is a major complication in hemizygous males with Fabry disease. This often results in end-stage renal failure (ESRF), requiring dialysis or transplantation, on average 10 years after the start of renal impairment. ESRF usually occurs between 40 and 50 years of age, but may occur much earlier. Although progression of renal disease can be rapid, it is variable and may depend on whether there is residual alpha-galactosidase enzyme activity and on environmental or genetic factors. Significant renal disease is much less common in women carriers of the disease. However, renal changes do occur, which may progress to ESRF as in male patients. PMID- 11758683 TI - Cardiac manifestations in Fabry disease. AB - Fabry disease is an X-linked recessive genetic disorder of glycosphingolipid metabolism, due to deficiency of the lysosomal enzyme alpha-galactosidase A. The disease is characterized by the progressive intracellular lysosomal accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. It has been reported that cardiac involvement could be the sole manifestation of the disease in some patients. Myocardial abnormalities are characterized mainly by left ventricular (LV) wall thickening without significant cavity dilatation, the most frequent abnormal structural pattern being concentric LV hypertrophy (LVH). In some patients the disease mimics a typical hypertrophic obstructive cardiomyopathy. According to our experience, systolic function is largely preserved in a large majority of affected individuals. In contrast, mild to moderate impairment of diastolic filling is a relatively common finding, representing probably the most important cause of dyspnoea in patients with Fabry disease. However, in a relatively large population of affected patients, severe diastolic dysfunction, typical of restrictive cardiomyopathy, was not found. Valvular structural abnormalities are frequent due to valvular infiltration. In several patients, hypertrophy of papillary muscles and/or systolic anterior motion of the mitral leaflets associated with LV outflow obstruction may aggravate the mitral valve dysfunction. We did not confirm the previously reported high prevalence of mitral valve prolapse. Valvular regurgitation seems to be relatively frequent but mostly non-significant. Electrocardiographic changes in Fabry disease are multiple and include atrioventricular (AV) conduction abnormalities (abbreviation of the P-R interval or AV blocks), signs of LVH and repolarization abnormalities. Our observations suggest that conduction defects and repolarization changes are present predominantly in subjects with LV structural abnormalities. Cardiac symptoms in patients with Fabry disease include shortness of breath on effort (related to LV diastolic dysfunction), vasospastic and/or exertional angina pectoris (due to LVH, endothelial dysfunction and/or fixed coronary artery stenosis) and syncope (related to AV blocks or LV outflow obstruction). The extent of cardiac involvement, in particular LV mass assessment, could represent an ideal surrogate endpoint for evaluating the efficacy of specific therapies. PMID- 11758684 TI - Lessons learned from the development of enzyme therapy for Gaucher disease. AB - Enzyme replacement therapy for the lysosomal storage disorders derives its impetus from the successes achieved in the treatment of Gaucher disease. After nearly two decades of persistent but unsuccessful efforts, the promise of therapy through enzyme replacement was losing credibility. Then, the fortunate intersection of two different lines of scientific research produced the necessary breakthrough. The dramatic responses to enzyme replacement therapy in patients with Gaucher disease made it immediately clear that this treatment approach was a success. Furthermore, the large number of patients with the disorder guaranteed commercial involvement. The lessons learned from the development of enzyme replacement therapy for Gaucher disease are broadly applicable to other lysosomal storage diseases and will be reviewed in this paper. PMID- 11758685 TI - Clinically relevant therapeutic endpoints in type I Gaucher disease. AB - The introduction of enzyme supplementation therapy for Gaucher disease has had a great impact on the lives of many patients. Organomegaly, cytopenia and bone disease have been shown to improve in response to treatment, resulting in an improvement in quality of life. However, the assessment of organ system involvement is not always done in such a way that the relationship with clinically relevant endpoints is clear. The lack of adequately validated methods of assessment, especially for bone disease, has hindered the establishment of treatment goals and guidelines for treatment optimization. PMID- 11758686 TI - Global analysis of regional differences in craniometric diversity and population substructure. AB - Estimates of genetic diversity in major geographic regions are frequently made by pooling all individuals into regional aggregates. This method can potentially bias results if there are differences in population substructure within regions, since increased variation among local populations could inflate regional diversity. A preferred method of estimating regional diversity is to compute the mean diversity within local populations. Both methods are applied to a global sample of craniometric data consisting of 57 measurements taken on 1734 crania from 18 local populations in six geographic regions: sub-Saharan Africa, Europe, East Asia, Australasia, Polynesia, and the Americas. Each region is represented by three local populations. Both methods for estimating regional diversity show sub-Saharan Africa to have the highest levels of phenotypic variation, consistent with many genetic studies. Polynesia and the Americas both show high levels of regional diversity when regional aggregates are used, but the lowest mean local population diversity. Regional estimates of F(ST) made using quantitative genetic methods show that both Polynesia and the Americas also have the highest levels of differentiation among local populations, which inflates regional diversity. Regional differences in F(ST) are directly related to the geographic dispersion of samples within each region; higher F(ST) values occur when the local populations are geographically dispersed. These results show that geographic sampling can affect results, and suggest caution in making inferences regarding regional diversity when population substructure is ignored. PMID- 11758687 TI - A worldwide analysis of AG molecular diversity inferred from serology. AB - Ten population samples from different geographic origins were tested serologically for the AG polymorphism of human beta-lipoproteins. Their haplotype frequencies were used with previously published data to perform a wide analysis of AG genetic differentiations throughout the world. Coancestry coefficients were computed from weighted F(ST)s among populations by using a matrix of molecular distances among AG haplotypes, which is here determined on the basis of DNA studies. Coancestry coefficients derived from unweighted F(ST)s and more classical Prevosti distances were computed on the same data and used for a comparison. In all cases a highly significant correlation was found between genetics and geography on a worldwide scale, while the significance of the correlation with linguistics differed. A test of significance of the pairwise F(ST)s among populations also gave different results depending on whether the molecular distance matrix among AG haplotypes was included. Globally, this study shows that in spite of being highly significantly correlated to each other, different genetic distance measures can lead to different interpretations of the same data set. Moreover, the elucidation of the molecular models related to the presently known serological polymorphisms may represent an additional tool for analyzing such polymorphisms in human population genetics studies. PMID- 11758688 TI - History and origin of beta-thalassemia in Turkey: sequence haplotype diversity of beta-globin genes. AB - In the present study we report the sequence haplotypes associated with 22 beta globin gene mutations present in Turkey. Nine nucleotide polymorphisms and an (AT)xTy motif located at the 5' end of the beta-globin gene form the sequence haplotypes that were investigated in 204 unrelated beta-thalassemia and wild-type chromosomes from Turkey. Twelve sequence haplotypes were observed in the chromosomes analyzed and haplotypic heterogeneity was found in the wild-type beta globin genes. Samples from the Black Sea region demonstrated a remarkable level of haplotypic heterogeneity in contrast to the homogeneity present in Central Anatolian samples. Of the 22 beta-globin mutations analyzed, 18 were related with single sequence haplotypes. This simple association led to the attempt to determine the origin of these mutations by comparing their frequencies in Turkey with those in other countries and/or the world distribution of the haplotypes carrying them. However, the presence of several exceptions for the "one haplotype/one mutation" rule showed that the beta-globin gene cluster is far from static. Each of the IVS-I-110 (G-->A), Cd 39 (C-->T), IVS-I-6 (T-->C), and -30 (T ->A) beta-globin mutations was associated with a minimum of two sequence haplotypes. This fact is best explained by the likelihood of strong recombination mechanisms taking place, rather than by assuming multiple origins for each of these alleles. According to our results, malarial selection for the oldest beta thalassemia allele in Anatolia (i.e., IVS-I-110 G-->A) may have occurred between 6500 and 2000 B.C. From that date on, most of the common beta-thalassemia mutations in Turkey were established, and by the 13th century A.D. most of them were brought to frequencies close to those observed at present. PMID- 11758689 TI - Sub-Saharan genetic contribution in Morocco: microsatellite DNA analysis. AB - Northwest African populations occupy a strategic geographical area that has always been a zone of influence for diverse human groups from different regions. This article focuses on the analysis of the genetic contribution of sub-Saharan African populations by means of four short tandem repeat (STR) systems (HUMTPOX, HUMVWA31/A, HUMTHO1, and HUMF13B), which have proven informative in establishing genetic relationships between human populations. Genetic trees and multivariate analyses of European and Near Eastern populations show that the Moroccan population shares a common genetic substrate with all of them. However, the latter defines a specific lineage. Evolutionary factors inherent in the population's geographical isolation in early times, together with genetic flow from sub-Saharan populations (mainly as reflected by HUMF13B and HUMTPOX), appear to be particularly relevant in understanding the peculiarities of the genetic character of the present-day population. PMID- 11758690 TI - Authenticating ancient human mitochondrial DNA. AB - The use of ancient DNA techniques in human studies has been hampered by problems of contamination with modern human DNA. The main problem has been that the object of study belongs to the same species as the observer, and the complete elimination of the contamination risk is seemingly unlikely. Contamination has even been detected in the most specialized laboratories in this field. In these kinds of studies it is therefore very important to detect contamination and to distinguish contaminants from authentic results. Here, we report the use of a strategy to authenticate the identity of ancient mitochondrial DNA (mtDNA), based on the previously established relationship between D-loop sequence substitutions and haplogroup-specific restriction site changes. Forty-four individuals from a 16th-century necropolis were analyzed, from which 28 control region sequences were obtained. These sequences were preclassified into haplogroups, according to the observed motifs. Subsequently, the DNA extracts from which the sequences were obtained, along with independent extracts of subsets of the same individuals, were subjected to restriction fragment length polymorphism (RFLP) analysis to compare and corroborate the results. Using this approach, 24 sequences were authenticated, while two were discarded because of result mismatches. The final distribution of the haplogroups in the sample, and the differences in the sequences, are two additional criteria of authentication. PMID- 11758691 TI - Mitochondrial DNA variation in Nicobarese Islanders. AB - The aboriginal populations living in the Nicobar Islands are hypothesized to be descendants of people who were part of early human dispersals into Southeast Asia. However, analyses of ethnographic histories, languages, morphometric data, and protein polymorphisms have not yet resolved which worldwide populations are most closely related to the Nicobarese. Thus, to explore the origins and affinities of the Nicobar Islanders, we analyzed mitochondrial DNA (mtDNA) hypervariable region 1 sequence data from 33 Nicobarese Islanders and compared their mtDNA haplotypes to those of neighboring East Asians, mainland and island Southeast Asians, Indians, Australian aborigines, Pacific Islanders, and Africans. Unique Nicobarese mtDNA haplotypes, including five Nicobarese mtDNA haplotypes linked to the COII/tRNA(Lys) 9-bp deletion, are most closely related to mtDNA haplotypes from mainland Southeast Asian Mon-Kmer-speaking populations (e.g., Cambodians). Thus, the dispersal of southern Chinese into mainland Southeast Asia may have included a westward expansion and colonization of the islands of the Andaman Sea. PMID- 11758692 TI - One hundred years of growth: the evolution of height, mass, and body composition in Australian children, 1899-1999. AB - This paper summarizes 41 reports on the height and mass of Australian children aged between 5.00 and 16.99 years between 1899 and 1999. In all, data on 644,613 children were collated, including individual data on 68,196 children. After primary data treatment to correct for methodological and statistical artifacts, regressions were calculated to quantify the rate of change of height and mass over time. Distributional analysis was used to probe for changes in skewness of mass values, indicative of differentially greater increases at higher percentiles. In addition, studies reporting skin fold measurements were analyzed to assess changes in subcutaneous adiposity since 1976. The results show that height has been increasing at a rate of about 1.02 cm.decade(-1), and mass at a rate of about 0.99 kg.decade(-1). The height and mass of children continue to increase, after a slowing down in the rate of increase between 1950 and 1980. Increases in mass at the higher percentiles have been much greater than at lower percentiles, particularly since the mid-1980s, suggesting that the incidence of obesity is increasing in Australian children. Furthermore, a steady linear increase in subcutaneous skin fold thicknesses since 1976 suggests that the overall level of fatness is increasing in Australian children. These findings indicate that Australian children are following trends becoming evident elsewhere in the developed world, and that we may see an increasingly large subset of increasingly obese children in the early years of the 21st century. PMID- 11758694 TI - Variability of six STR loci in populations from Central Spain. AB - Allele frequency distributions of six short tandem repeat (STR) loci, HUMTH01, HUMFES/FPS, HUMTPOX, HUMVWF/A31, HUMF13B, and HUMLPL, were determined in a population (101 individuals) of the Vera-Jerte region in West Central Spain. Amplified products were electrophoresed on denaturing polyacrylamide gels and silver-stained. The exact test demonstrated that none of the six loci deviated from Hardy-Weinberg equilibrium. R-matrix analysis in relation to other European samples agrees well with genetic distance results of Reynolds et al. (1983). Comparisons show that our population comes reasonably well within the range of variation of other European samples, and that the representation of these samples on the genetic map indicates a close relation between geographical location and distribution in the diagram. PMID- 11758693 TI - Red cell genetic abnormalities, beta-globin gene haplotypes, and APOB polymorphism in the Great Andamanese, a primitive Negrito tribe of Andaman and Nicobar Islands, India. AB - The Great Andamanese are a primitive Negrito tribe of the Andaman and Nicobar Islands, India, with a total population of 37. We studied 29 individuals from eight families from this population for abnormal hemoglobins, G6PD deficiency, DNA haplotypes, and apolipoprotein B (APOB, gene) polymorphism. Hb E was detected in five individuals, the prevalence of Hb E heterozygotes being 14.3%. One individual had beta-thalassemia trait. One female was G6PD deficient and showed the G6PD Orissa mutation. Haplotype analysis of the beta-globin gene cluster showed that the betaE chromosomes were linked to two haplotypes (- - - - - + + and + + - + + + +) representing the framework 1 gene, whereas the betaA chromosomes showed eight different haplotypic patterns corresponding to framework 1 and 3 genes. APOB polymorphism analysis showed that the 631-base-pair (bp) allele was the predominant one with a high homozygosity rate, which could be due to the higher rate of inbreeding in this isolated group. The presence of Hb E and our findings on haplotype analysis supports the hypothesis that the Great Andamanese are reasonably believed to be the surviving representatives of the Negrito race that once flourished in the entire Southeast Asian region in ancient times. PMID- 11758695 TI - Identification of base substitutions in ten types of rare variants of phosphoglucomutase-1 (PGM1) encountered in Japanese. AB - In a previous starch-gel electrophoresis study of erythrocyte phosphoglucomutase 1 (PGM1) in 23,095 Japanese from Hiroshima and Nagasaki, we detected 14 types of rare variant alleles. To determine sequence differences in these rare alleles, cell lines were established from peripheral B-lymphocytes from 24 unrelated individuals in whom nine types of rare variants are presumed to exist on the basis of earlier electrophoresis studies. cDNAs reverse transcribed from mRNAs extracted from these cell lines were amplified by polymerase chain reaction and sequences determined. Amino acid substitution types were deduced from each cDNA sequence. Although two individuals were reported to have an identical electromorph (PGM1 4HR3), sequence analysis revealed that alleles encoding these electromorphs possessed different base substitutions, and one was renamed PGM1 4HR4. As the amino acid substitution of ten different variants could be deduced by cDNA sequence in this study, the effect of each amino acid substitution on enzyme activity could be precisely simulated. The secondary structure of each variant predicted by computer simulations revealed that very decreased activity observed on PGM1 4HR2 protein was caused by significant secondary structure change introduced by the amino acid substitution. On the basis of the crystal structure, the amino acid substitutions of the ten types of rare variants seem to be outside the active center of this enzyme. PMID- 11758696 TI - North African genes in Iberia studied by Y-chromosome DNA haplotype 5. AB - The frequency of haplotype 5 at the Y-chromosome-specific DNA polymorphism (p49/TaqI) was reported in a study of 487 males originating from five different geographic locations in Iberia and North Africa. The highest frequency of haplotype 5 (68.9%) was previously observed in Berbers from Morocco, and it has been established that this haplotype is a characteristic Berber haplotype in North Africa. The relative frequencies of haplotype 5 distribution show a geographical gradient of decreasing frequency according to latitude in Iberia: 40.8% in Andalusia, 36.2% in Portugal, 12.1% in Catalonia, and 11.3% in the Basque Country; such a cline of decreasing frequency of haplotype 5 from the south to the north in Iberia clearly establishes a gene flow from North Africa towards Iberia. PMID- 11758697 TI - Mirror, mirror on the wall, who is the ugliest of them all? The psychopathology of mirror gazing in body dysmorphic disorder. AB - Patients with Body Dysmorphic Disorder (BDD) may spend many hours in front of a mirror but little is known about the psychopathology or the factors that maintain the behaviour. A self-report mirror gazing questionnaire was used to elicit beliefs and behaviours in front of a mirror. Two groups were compared, which consisted of 55 controls and 52 BDD patients. RESULTS: Prior to gazing, BDD patients are driven by the hope that they will look different; the desire to know exactly how they look; a belief that they will feel worse if they resist gazing and the desire to camouflage themselves. They were more likely to focus their attention on an internal impression or feeling (rather than their external reflection in the mirror) and on specific parts of their appearance. They were also more likely to practise showing the best face to pull in public or to use "mental cosmetic surgery" to change their body image than controls. BDD patients invariably felt worse after mirror gazing and were more likely to use ambiguous surfaces such as the backs of CDs or cutlery for a reflection. CONCLUSION: Mirror gazing in BDD consists of a series of complex safety behaviours. It does not follow a simple model of anxiety reduction that occurs in the compulsive checking of obsessive-compulsive disorder. The implications for treatment are discussed. PMID- 11758699 TI - Parent-child interactions and anxiety disorders: an observational study. AB - Past research has indicated a potential link between anxiety and parenting styles that are characterised by control and rejection. However, few studies have utilised observational methods to support these findings. In the current study, mother-child interactions were observed while the child completed two difficult cognitive tasks. The sample consisted of clinically anxious children (n=43), oppositional defiant children (n=20) and non-clinical children (n=32). After adjusting for the age and sex of the child, mothers of anxious children and mothers of oppositional children displayed greater and more intrusive involvement than mothers of non-clinical children. Mothers of anxious children were also more negative during the interactions than mothers of non-clinical children. The differences between anxious and non-clinical interactions were equivalent across three separate age groups. The results support the relationship between an overinvolved parenting style and anxiety but question the specificity of this relationship. PMID- 11758698 TI - A longitudinal study of the etiology of separation anxiety. AB - A longitudinal examination of the relation between separation experiences and the development of separation anxiety at age 3, 11 and 18 years was conducted. Three associative pathways were assessed. Conditioning events were not related to separation anxiety at age 3. Vicarious learning (modelling) in middle childhood (age 9 years) was the conditioning variable most strongly related to separation anxiety at age 11, accounting for 1.8% of the variance in symptoms. Separation experiences (hospitalisations) before the age of 9 were inversely correlated with separation anxiety at age 18. That is, more overnight hospital stays in childhood were related to less separation anxiety in late adolescence. However, none of these conditioning correlates remained significant predictors of separation anxiety in adjusted regression models. In contrast, certain "planned" separations in early-mid childhood were associated with lower levels of separation anxiety at later ages. Generally, the findings were consistent with predictions from the non associative theory of fear acquisition. That vicarious learning processes appeared to modulate, albeit to a minor degree, the expression of separation anxiety during mid-late childhood suggests that there may be critical periods during which some individuals are susceptible to the interactive effects of both associative and non-associative processes. These findings serve to illustrate the complexity of fear acquisition, the relevance of developmental factors and the likely interplay between associative and non-associative processes in the etiology of fear and anxiety. PMID- 11758700 TI - Proprioception in somatoform disorders. AB - 20 patients with somatoform disorders as defined by DSM-IV and 20 healthy controls were examined for their proprioception. Several psychophysiological theories of somatoform disorders suggest biased proprioceptive abilities. The primary question is, whether we may find an inaccurate myogen perception in somatization as suggested by the approach of Bischoff or a more precise proprioception as may be derived from concepts of a higher awareness of body reactions. Furthermore it is expected, that somatoform patients perceive their muscle tension more intensely than do healthy subjects. Proprioceptive abilities were tested using a visual EMG biofeedback task. Resulting objective data and subjective ratings were analyzed within a psychophysiological regression approach which allows one to estimate the reliability, precision and intensity of proprioception. Results revealed that somatoform subjects demonstrated a more precise but not a more intense perception of muscle tension than did healthy controls. PMID- 11758701 TI - On becoming neutral: effects of experimental neutralizing reconsidered. AB - Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier. PMID- 11758702 TI - Long term course of chronic posttraumatic stress disorder in traffic accident victims: a three-year prospective follow-up study. AB - The purpose of the present study was to gather prospective longitudinal data on the long-term course and outcome of chronic posttraumatic stress disorder (PTSD). The target population for this study was 74 injured traffic accident victims who had been previously followed-up for one year after the trauma. Nineteen of the original 24 PTSD subjects (79%) and 39 of the original 50 Non-PTSD subjects (78%) were available for this study, which took place during the fourth year after the accident. Our results show that 10 (53%) of the 19 patients with PTSD at one-year still suffered from PTSD after another two-year follow-up interval, while 9 recovered from PTSD during this follow-up period. Only 2 of the 39 without PTSD at one year developed delayed onset PTSD. The best predictor of recovery from chronic PTSD was the initial level of posttraumatic reaction immediately after the accident. These results demonstrate that spontaneous recovery from PTSD can occur even among patients who are currently considered chronic. Severity of initial reaction to the trauma appears to be a major risk factor for non remitting chronic PTSD. PMID- 11758703 TI - Evolution of incidentally-discovered fusiform aneurysms of the vertebrobasilar arterial system: neuroimaging features suggesting progressive aneurysm growth. AB - This study investigated the natural history and biological behavior of incidental fusiform aneurysms in four patients with incidental fusiform aneurysms of the vertebrobasilar arterial system who had been followed up for more than 3 years (mean 3.5 years). Two lesions remained the same size, and two lesions gradually grew. Angiography showed the non-growing fusiform aneurysms as a circumferentially or unilaterally fusiform dilatation of a short segment of the vertebral artery with smooth walls and a steep slope of the dilatation, and the growing fusiform aneurysms as unilaterally fusiform involving a long segment of the vertebral artery or basilar artery with irregular walls and a gentle slope of dilatation. Magnetic resonance (MR) imaging demonstrated the non-growing fusiform aneurysms as a signal-void area, and the growing fusiform aneurysms as high and intermediate signals in addition to the normal flow void. The heterogeneous MR intensities probably correspond to turbulent flow, laminar flow, thrombosis, or intramural hematoma. Differentiation of growing and non-growing fusiform aneurysms is very difficult at the initial diagnosis. However, enlargement of the fusiform aneurysms is consistent with hemorrhage into the aneurysmal wall, which is confirmed by MR imaging. Fusiform aneurysms with the characteristics of the growing aneurysms cannot be overlooked because of the potential to develop into giant fusiform aneurysms which are very difficult to manage therapeutically. PMID- 11758704 TI - Deformation of the ventrolateral medulla oblongata by subarachnoid hemorrhage from ruptured vertebral artery aneurysms causes neurogenic pulmonary edema. AB - The occurrence of neurogenic pulmonary edema (NPE) associated with subarachnoid hemorrhage (SAH) due to ruptured aneurysm was analyzed in 48 consecutive patients. Correlations of the location of the aneurysm, clinical grade, amount of subarachnoid clot, and severity of NPE were examined. NPE was observed in 29.4% of all SAH cases, but the incidence was significantly higher in cases of ruptured vertebral artery (VA) aneurysm. Clinical grade, severity of NPE, and deformation of the medulla oblongata were studied in the five cases of ruptured VA aneurysm. Deformation of the ventrolateral medulla oblongata was observed in all patients. Asymmetry index of the medulla oblongata measured on the axial computed tomography scan was correlated with the severity of NPE. Severity of NPE tended to correlate with deformation of the medulla oblongata. NPE associated with ruptured VA aneurysm is caused by deformation of the ventrolateral site of the medulla oblongata by the localized hemorrhage. PMID- 11758705 TI - Tight Sylvian cisterns associated with hyperdense areas mimicking subarachnoid hemorrhage on computed tomography--four case reports. AB - Four patients with supratentorial mass lesions (two chronic subdural hematomas, one acute epidural hematoma, and one acute subdural hematoma) showed hyperdense sylvian cisterns on computed tomography (CT). Association of subarachnoid hemorrhage was suspected initially, but was excluded by intraoperative observation or postoperative lumbar puncture. CT showed disappearance of the hyperdense areas just after evacuation of the mass lesions. The hyperdense areas are probably a result of the partial volume phenomenon or concentrations of calcium deposits rather than abnormally high hematocrit levels, which were not found in these patients. PMID- 11758706 TI - Traumatic basilar artery occlusion caused by a fracture of the clivus--case report. AB - A 56-year-old man presented with a rare traumatic basilar artery occlusion caused by a fracture of the clivus. He fell from the height of 2 meters and immediately fell into a coma. Head computed tomography (CT) revealed an open depressed fracture, an acute epidural hematoma 1 cm thick in the left middle frontal fossa, and a longitudinal fracture of the clivus. Emergency removal of the hematoma was performed with cranioplasty. Head CT 8 hours 50 minutes after injury showed infarctions in the brain stem, cerebellum, and occipital lobes. Cerebral angiography revealed occlusion of the basilar artery in the middle part of the clivus. The patient died after 3 days. Autopsy revealed that the basilar artery was trapped in the clivus fracture site. Vertebrobasilar artery occlusion due to trapping in a clivus fracture has a very poor prognosis. Diagnosis is difficult and generally only confirmed at autopsy. Cerebral angiography is recommended in a patient in a deep coma without massive brain contusion at the early stage of head injury to identify the possibility of vertebrobasilar artery occlusion in a clivus fracture. PMID- 11758707 TI - Infra-posterior inferior cerebellar artery aneurysm arising after occlusion of the ipsilateral vertebral artery--case report. AB - An 85-year-old woman had subarachnoid hemorrhage due to rupture of a very rare left infra-posterior inferior cerebellar artery (PICA) aneurysm, a saccular aneurysm located proximally at the junction of vertebral artery (VA) and PICA. Right vertebral angiography demonstrated the aneurysm since the left VA was occluded in the extracranial portion. The aneurysm projected in the opposite direction to common VA-PICA aneurysms. The angiographical and intraoperative findings imply this rare aneurysm resulted from the hemodynamic changes caused by the VA occlusion. Detailed exploration of angiography is emphasized to detect such rare aneurysms among the diversity of hemodynamic patterns in elderly patients with subarachnoid hemorrhage. PMID- 11758708 TI - Intratumoral hemorrhage from a posterior fossa tumor after cardiac valve surgery- case report. AB - A 53-year-old woman suffered intracranial hemorrhage from a cerebellar tumor several days after aortic valve replacement. Surgical intervention was not performed because the patient refused blood infusion for religious reasons (Jehovah's Witness). Instead, the anticoagulation therapy was interrupted for a week, and the patient was conservatively treated with administration of mannitol and steroid. The anticoagulation therapy was restarted 7 days after the hemorrhage. The intratumoral hemorrhage did not recur, and no systemic embolism occurred. The tumor was treated with gamma knife radiosurgery 6 weeks after the hemorrhage, under the radiological diagnosis of meningioma. Anticoagulation therapy is routinely used for patients following cardiac surgery to decrease the risk of thromboembolic complications, but also increases the risk of hemorrhagic events which often involve the central nervous system. Temporary discontinuation of anticoagulation therapy is an option for intratumoral hemorrhage in patients with replacement heart valves, and patients with known brain tumors should be informed about the risk of intracranial hemorrhage before cardiac surgery. PMID- 11758709 TI - Malignant schwannoma of the sciatic nerve originating in a spinal plexiform neurofibroma associated with neurofibromatosis type 1--case report. AB - A 26-year-old man with neurofibromatosis type 1 (NF1) presented with a giant malignant schwannoma of the sciatic nerve. The differential diagnosis of malignant peripheral nerve sheath tumor (MPNST) was based on clinical, radiological, and histological evidence. The tumor apparently originated in a spinal plexiform neurofibroma. The lesion was resected totally without neural damage to the sciatic nerve. However, the tumor recurred within 2 months. The patient died of unknown factors probably associated with the spinal involvement. MPNST associated with NF1 has a poor prognosis due to recurrence or metastasis despite complete macroscopic removal. PMID- 11758710 TI - Familial multiple trichoepithelioma associated with subclavian-pulmonary collateral vessels and cerebral aneurysm--case report. AB - A 63-year-old woman presented with cerebellar infarction caused by occlusion of the right posterior inferior cerebellar artery. She had papules on her face that were identified histologically as multiple trichoepithelioma. Angiography revealed right subclavian-pulmonary collateral vessels and a cerebral aneurysm arising from the bifurcation of the right middle cerebral artery. Her grandmother, mother, and uncle had had similar papules, and the deaths of her mother and uncle were due to subarachnoid hemorrhage. PMID- 11758711 TI - Metastatic brainstem tumor manifesting as hearing disturbance--case report. AB - A 53-year-old male, who had undergone a left upper lung lobectomy for cancer 2 years previously, presented with metastatic brainstem tumor manifesting as hearing disturbance. At first an otorhinolaryngologist treated him for senile sensorineural hearing disturbance. However, he suffered gait ataxia and was referred to our department. On admission, neurological examination found mild cerebellar ataxia on the left and gait unsteadiness. Neurootological analysis revealed central-type sensorineural hearing disturbance on the left both in the pure tone audiogram and speech discrimination test. Neuroimaging studies revealed a ring-like enhanced mass centered in the ventral left middle cerebellar peduncle, partly extending to the inferior cerebellar peduncle. Peritumoral edema extending to the ipsilateral cochlear nucleus was recognized. He underwent surgery via a left lateral suboccipital transcondylar approach. The histological diagnosis was adenocarcinoma identical with the primary lung cancer. Intra-axial brainstem metastatic lesion can be a cause of hearing disturbance, so should be included in the differential diagnosis for a patient complaining of hearing disturbance, especially with a past history of cancer. PMID- 11758712 TI - Computer-assisted neurosurgical navigational system for transsphenoidal surgery- technical note. AB - Transsphenoidal surgery carries the risk of carotid artery injury even for very experienced neurosurgeons. The computer-assisted neurosurgical (CANS) navigational system was used to obtain more precise guidance, based on the axial and coronal images during the transsphenoidal approach for nine pituitary adenomas. The CANS navigator consists of a three-dimensional digitizer, a computer, and a graphic unit, which utilizes electromagnetic coupling technology to detect the spatial position of a suction tube attached to a magnetic sensor. Preoperatively, the magnetic resonance images are transferred and stored in the computer and the tip of the suction tube is shown on a real-time basis superimposed on the preoperative images. The CANS navigation system correctly displayed the surgical orientation and provided localization in all nine patients. No intraoperative complications were associated with the use of this system. However, outflow of cerebrospinal fluid during tumor removal may affect the accuracy, so the position of the probe when the tumor is removed must be accurately determined. The CANS navigator enables precise localization of the suction tube during the transsphenoidal approach and allows safer and less invasive surgery. PMID- 11758713 TI - Stages of development of the ribosome-lamella complex: an ultrastructural study. AB - Ribosome-lamella complexes (RLC) are intracytoplasmic organelles observed in a wide variety of disorders, but mostly in hematologic malignancies. Although their close topographic relationship with rough endoplasmic reticulum (RER) suggests their derivation from it, their development and functional role are unclear. Their maturation phases were studied in 20 cases (19 hematologic neoplasms and 1 parathyroid adenoma) where electron microscopy had evidenced their presence. In 19 of thesecases, RLC were in an advanced stage of maturation, whereas in one (acute monoblastic leukemia) they were observed in the early stages of development and appeared to arise from peculiar RER configurations within blast cells, which were rich in both organelles. In this case, the authors observed numerous RER cisternae with distinctive cylindric, concentric and/or whorl configurations, RLC associated and not associated with these configurations, and intermediate structures. The latter were characterized by lamellae devoid of ribosomes oriented parallel to the RER configurations. Reticulum configurations were observed in no other case. The ultrastructural aspects observed in these 20 cases suggest that RLC synthesis proceeds as follows: (1) arrangement of RER in cylindric configurations; (2) synthesis of lamellae oriented parallel to the cylindric configurations (pre-RLC); (3) formation of RLC when ribosomes appear between the lamellae associated with configurations (immature RLC); (4) formation of mature RLC with disappearance of the reticulum. PMID- 11758714 TI - Desmin-Related myopathy: ultrastructural findings. PMID- 11758715 TI - Expression of EGFR family and steroid hormone receptors in ductal carcinoma in situ of the breast. AB - The expression of EGFR family and steroid hormone receptors was examined in a series of 40 cases of pure ductal carcinoma in situ (DCIS) of the breast by immunohistochemical staining of paraffin-embedded sections. Hematoxylin and eosin stained sections were used to classify the tumors according to the published criteria by Holland et al. (Holland R, Peterse JL, Millis RR, et al. Semin Diagn Pathol. 1994;1 1:167-180). Of the tumors 48% were immunoreactive for EGFR, 63% for c-erbB-2, 78% for c-erbB-3, 95% for c-erbB-4, 88% for estrogen receptor (ER) and 80% for progesterone receptor (PR). Statistically significant association between histological grade (differentiation) and c-erbB-2 protein expression was seen (p <.001). In addition, expression of c-erbB-4 protein was associated with c erbB-2 (p=.004), c-erbB-3 (p=.058), ER (p=.002) and PR (p=.004). It is concluded that c-erbB-2 expression in DCIS is associated with high-grade pathological features, and a higher c-erbB-2 expression is seen in DCIS than in invasive breast carcinomas. A possible association between extensive expression of c-erbB 4 and steroid hormone receptors in proliferative and premalignant breast epithelial cells and the c-erbB-2 expression in DCIS and invasive breast carcinomas is discussed. PMID- 11758716 TI - Diagnosis of congenital hypothyroidism from human anagen scalp hair by infrared microspectroscopy. AB - A highly efficient Fourier transform infrared (FT-IR) microscopy was used to determine the biophysical structure of anagen scalp hair roots of neonates suffering from congenital hypothyroidism (CH) due to ectopic thyroid. The present results indicate that the lower composition near 1,053 cm(-1) (also assigned to the aromatic iodide stretching band) in the infrared (IR) spectra of the hair roots for CH patients was directly associated with the lower serum level of T4 and fT4, and the elevated TSH levels determined by RIA method. This strongly implies the lower evidence of the aromatic iodide stretching band in the IR spectra of hair roots. These findings suggest that FT-IR microscopy has the potential to become a good diagnostic tool and that hair can be useful as a genetic marker. PMID- 11758717 TI - Thyroid clear cell adenoma with marked dilatation of membranous structures: electron-microscopic study. AB - The electron-microscopic features of a thyroid follicular adenoma with clear cell change is described. The tumor was 7 mm in size and located in the upper portion of the left lobe of the thyroid of a 29-year-old Japanese female. Its cut surface was pale brown in color and well demarcated. The lesion consisted of solid nests with pinpoint lumina. The cytoplasm of the tumor cells was completely clear, but slightly vesicular without oncocytic change. Electron-microscopic examination revealed that the cytoplasm of the tumor cells was filled with numerous empty vacuoles. The vacuoles consisted of dilated membranous structures, indicating that they had been formed from rough endoplasmic reticulum and Golgi apparatus. There was no accumulation of glycogen, mucin, or lipid. The dilated membranous structures in the cytoplasm may be related to the increased thyroglobulin synthesis by the tumor. PMID- 11758718 TI - Unique cellular features in atypical adenomatous hyperplasia of the lung: ultrastructural evidence of its cytodifferentiation. AB - Atypical adenomatous hyperplasia (AAH) of the lung could be a good material to understand the histogenesis of peripherally occurring, well-differentiated adenocarcinoma. However, its true biological significance remains to be clarified. The authors present the histomorphological studies of this lesion and compare the ultrastructure with that of nonmucinous bronchioloalveolar carcinoma (BAC) to define characteristic features of AAH. Light microscopy showed the well preserved pulmonary architecture, proliferated neoplastic cells without marked cellular atypia, and no transitional area to obvious adenocarcinoma. Intranuclear inclusion was present in a large number of neoplastic cells. Electron microscopy revealed that cuboidal or low columnar neoplastic cells proliferated actively but were not crowded on slightly thickened fibrous alveolar septa with both Clara like granules and small lamellar bodies in the cytoplasm resembling that of Clara cell and type 2 pneumocyte. Some of the nuclei had characteristic invaginations of its nuclear membrane. Although the findings appear to be nonspecific for AAH, the authors emphasize that AAH is an alveolar intraepithelial neoplasia that represents a very early stage in the continuous developmental spectrum of adenomatous neoplasia in the bronchioloalveolar region corresponding to dysplasia or intraepithelial neoplasia in other organs, and will give the significance to speculate its histogenesis. PMID- 11758719 TI - Biodegradation of titanium implants after long-time insertion used for the treatment of fractured upper and lower jaws through osteosynthesis: element analysis by electron microscopy and EDX or EELS. AB - Twelve patients underwent an osteosynthesis with titanium to treat upper and lower jaw fractures. Six to 12 months later, the miniplates were removed. Tissue samples were analyzed by light and electron microscopy for detection of a metallosis. The analysis showed new bone formation like callus tissue around the miniplates. In some cases small, rounded deposits and accumulation of colloid like particles located next to bigger titanium artifacts were detected in the cytoplasm of histiocytes and in the matrix of connective tissue. The titanium was identified by elemental analysis using EDX in SEM as well as by EELS and electron diffraction in TEM. Both kinds of particles contain titanium, but they seem to be different in composition and derivation. The bigger particles seem to consist of metallic titanium and sourced by working on the metallic implants during the implantation itself. On the other hand, the colloidal-like, small, rounded particles in tissue macrophages and outside the cells in the matrix of connective tissue are presumably of other origin; for example, they could be derived from biodegradation and chemical conversion of the metallic implants. The titanium miniplates were examined before and after implantation by using ESCA technique and revealed metallic titanium and different compositions with other elements. The amount of titanium load of the tissue was very low in most cases and presumably not of biomedical relevance. PMID- 11758720 TI - Myofibrosarcoma of the upper jawbones: a clinicopathologic and ultrastructural study of two cases. AB - Two problematic spindle cell sarcomas involving upper jawbones in two adult male patients have been studied by histology, immunohistochemistry, and transmission electron microscopy, and respectively graded as low-grade malignancy and high grade malignancy. While any single methodological study did not allow confident classification of them into one or other of the classical categories of spindle cell sarcomas (fibrosarcoma versus leiomyosarcoma), the overall contribution from all three methodologies ultimately allowed them to be categorized as sarcomas with myofibroblastic differentiation. Histologically, both tumors had morphological features of an amalgama between neoplastic fibroblasts and smooth muscle cells. Immunohistochemically, both tumors expressed reactivity only for muscle specific actin and alpha smooth muscle actin, in addition to vimentin. Ultrastructurally, both tumors, while showing fibroblast-like cytoplasmic features, had a spurious and imperfectly organized cell surface defying convincing classification into any of specific categories (i.e., both appeared in terms of ultrastructure as poorly differentiated sarcoma, the former with low level of smooth muscle differentiation and possibly the presence of some fibronexus component, the latter with no smooth muscle differentiation but with possible evidence of very rare fibronectin fibril). Therefore, on balance, the most tenable diagnosis seemed to us that of a myofibrosarcoma in both cases. This work is presented considering the fact that myofibrosarcoma currently represents a topical theme of debate, and that this is the first report in medical literature concerning with myofibrosarcomas of the head and neck area in adults. PMID- 11758721 TI - Mixed tumors, myoepitheliomas, and oncocytomas of the soft tissues are likely members of the same family: a clinicopathologic and ultrastructural study. AB - Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances (epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S 100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial derived tumor family are given. PMID- 11758722 TI - Genetic and environmental influences on social support in later life: a longitudinal analysis. AB - The present study assessed the etiology of individual differences in social support over a six-year period. The availability of friend support, family support, and the perceived adequacy of the social support network was assessed three times using identical and same-gender fraternal twins reared together and reared apart from the Swedish Adoption/Twin Study of Aging. Results are based on the pairwise responses at the three occasions of measurement (labeled Q1, Q2, and Q3): 462 pairs at Q1 (assessed October 1984), 474 pairs at Q2 (October 1987), and 431 pairs at Q3 (October 1990). The longitudinal phenotypic correlations (ranging from .49 to .77) indicate that social support is a moderately stable characteristic. Qualitative genetic model-fitting analyses resulted in significant heritability estimates for the social support measures at all three measurement occasions. Results also indicate considerable stability in genetic effects across measurement occasions, with genetic correlations ranging from .65 to .97. Nonshared environmental influences were substantial contributors to social support, but were less stable across the measurement occasions, with correlations ranging from .07 to .52. PMID- 11758723 TI - Developing a measure of older adults' preparation for future care needs. AB - We developed a measure of preparation for future care needs (PFCN) which consists of three parts: a) attitudes regarding the usefulness of planning for future care needs and toward the risk of needing help or care in the future; b) processes of preparation (becoming aware of future care needs, avoidance of preparation, gathering information, developing preferences, concrete planning); and c) contents of planning for short- and long-term care needs. Validity data of the questionnaire are reported based on 590 older adults (65-92 years). Engaging in preparation processes was associated with habitual decision styles, higher satisfaction with preparation, and greater knowledge of services. Greater vulnerability to needing future care was associated with higher expectations of needing care and more preparation. Internal consistency and stability of the measure based on 96 seniors was acceptable for almost all scales. PMID- 11758724 TI - Subjective evaluation of health in old age: the role of immigration status and social environment. AB - The study investigated the role of immigration status on self-rated health, general health, and well-being among elderly persons by comparing two groups of elderly persons who immigrated from Eastern European countries to Israel-veterans and new immigrants. It also examined the factors that explain self-rated health in both groups. Data for this study (n = 784) were taken from a study based on structured home interviews of a random sample of Israeli Jewish elderly (70+) conducted in 1994. The results show that the new immigrants are younger and have higher education than the veterans, but their economic status is lower and they have a lower percentage of men and married persons. The new immigrants also rank themselves lower than the veterans on a variety of measures of health and psycho social well-being. It is suggested that the stress caused by immigration and factors related to the standard of living and health services in the countries of origin outweigh the relative advantage that the new immigrants have, in terms of age and education, in influencing their health and well-being. Self-rated health among the new immigrants is explained mainly by objective measures of health, economic status and a feeling of control over life, while among the veterans it is explained by these variables as well as by other psycho-social variables such as self-esteem and social support. These findings suggest careful analyses of subjective evaluations of health in different socio-cultural subgroups in society for theoretical reasons and for purposes of planning interventions directed to promote health and psycho-social well-being of elderly persons on the community level. PMID- 11758725 TI - Differential esterase expression in leaves of Manihot esculenta Crantz infected with Xanthomonas axonopodis pv. manihotis. AB - The polyacrylamide gel electrophoresis system (PAGE) and inhibition tests for biochemical characterization of alpha- and beta-esterases were used to obtain a functional classification of esterases in plants and to show a differential expression of esterases as markers of pathogenesis in cassava plants (Manihot esculenta Crantz). The characterization of alpha- and beta-esterases from leaves of M. esculenta by the PAGE system was possible using an extraction solution containing two phenol-complexing agents (PVP-40 and sodium metabisulfite), three antioxidant agents (EDTA, beta-mercaptoethanol, and DTT), and one quinone reducer (ascorbic acid). Fourteen esterase isozymes were detected in young unexpanded leaves of M. esculenta cultivars. The inhibition pattern of alpha- and beta esterases of M. esculenta showed that Est-9 is an arylesterase, and in the unexpanded leaves of the M. esculenta plants infected with Xanthomonas axonopodis pv. manihotis, the Est-7 beta-esterase showed the characteristic staining of an alpha/beta-esterase. This diffrential expression of Est-7 isozyme in young unexpanded leaves of cassava plants can be used as a marker of pathogenesis after infection with X. axonopodis pv. manihotis. PMID- 11758726 TI - Comparative analysis of genetic diversity among Indian populations of Scirpophaga incertulas by ISSR-PCR and RAPD-PCR. AB - Genetic variation between 28 Indian populations of the rice pest, Scirpophaga incertulas was evaluated using inter-simple sequence repeats (ISSR)-PCR assay. Nine SSR primers gave rise to 79 amplification products of which 67 were polymorphic. A dendrogram constructed from this data indicates that there is no geographical bias to the clustering and that gene flow between populations appears to be relatively unrestricted, substantiating our earlier conclusion based on the RAPD (random amplified polymorphic DNA) data. The dendrograms obtained using each of these marker systems were poorly correlated with each other as determined by Mantel's test for matrix correlation. Estimates of expected heterozygosity and marker index for each of these marker systems suggests that both these marker systems are equally efficient in determining polymorphisms. Matrix correlation analyses suggest that reliable estimates of genetic variation among the S. incertulas pest populations can be obtained by using RAPDs alone or in combination with ISSRs, but ISSRs alone cannot be used for this purpose. PMID- 11758727 TI - Restriction fragment length polymorphism (RFLP) in exon 2 of the BoLA-DRB3 gene in South American cattle. AB - The Bola-DRB3 gene participates in the development of the immune response and is highly polymorphic. For these reasons, it has been a candidate gene in studies of the genetic basis of disease resistance and in population genetic analysis. South American native cattle breeds have been widely replaced by improved exotic breeds leading to a loss of genetic resources. In particular, South American native breeds have high levels of fertility and disease resistance. This work describes genetic variability in the BoLA-DRB3 gene in native (Caracu, Pantaneiro, Argentinean Creole) and exotic (Holstein, Jersey, Nelore, Gir) cattle breeds in Brazil and Argentina. PCR-RFLP alleles were identified by combining the restriction patterns for the BoLA-DRB3.2 locus obtained with RsaI, BstY and HaeIII restriction enzymes. Allelic frequencies and deviations from the Hardy Weinberg equilibrium were also calculated. Analysis of the 24 BoLA-DRB3 PCR-RFLP alleles identified showed differences in the allele distributions among breeds. PMID- 11758728 TI - Molecular marker analysis of protein content using PCR-based markers in wheat. AB - Grain protein concentration (GPC) of hexaploid wheat is one of the important factors that determines the end-product quality as well as playing a pivotal role in human nutrition. In an attempt to identify PCR-based DNA markers linked to GPC, 106 recombinant inbred lines (RILs) were developed from a cross between two wheat cultivars PH132 and WL711, which differ significantly in GPC, by the single seed descent method. The RILs were phenotyped for GPC at two diverse agroclimatic locations, namely Pune and Ludhiana, to study the influence of genotype and environment interactions on this trait. The parents were screened with 85 inter simple sequence repeat (ISSR) primers and 350 random primers. The selective genotyping and whole population analysis revealed nine DNA markers associated with the trait. Three markers (UBC8441100, UBC8801000, and OPA4800) were observed to be associated with the trait in both locations, whereas two markers (OPH41400) and UBC873750) werefound to be specific to Pune, and four markers (OPM5870, OPO10870, OPV141200, and UBC8251000) were specific to Ludhiana. Together five markers at the Pune location representing five QTLs and seven markers at Ludhiana representing four QTLs accounted for 13.4 and 13.5% of total phenotypic variation, respectively. This study clearly demonstrates that GPC is highly influenced by the environment, and the applicability of ISSR and RAPD markers in finding regions on chromosomes associated with quantitative characters in wheat such as GPC. PMID- 11758729 TI - Tissue-specific and developmental effects of the easily shocked mutation on ethanolamine kinase activity and phospholipid composition in Drosophila melanogaster. AB - The easily shocked (eas) gene of Drosophila melanogaster encodes ethanolamine kinase (EK), the first step in phosphatidylethanolamine (PE) synthesis via the CDP-ethanolamine pathway Flies mutant for eas display a complex neurological phenotype. In this paper we look at the contribution of EK to lipid metabolism during Drosophila development with the goal of linking the eas biochemical defect with the organismal phenotype. Using a chromatography-based assay, EK activity was detected in wild-type flies throughout development. Most of the activity in the adult was present in heads, which is primarily tissue of neural origin. Flies mutant for eas showed severely reduced levels of activity at each stage assayed. Using standard extraction methods and thin layer chromatography, phospholipid composition was assayed in wholeflies and in heads. While PE levels were decreased significantly in both tissues, heads also had significantly less phosphatidylserine (PS). Therefore, decreases in both phospholipids may play a role in producing the aberrant phenotype in eas flies. PMID- 11758730 TI - A MnlI restriction site polymorphism in the interleukin-10 gene promoter. PMID- 11758731 TI - Basic biological research with the striated muscle by using cryotechniques and electron microscopy. AB - Several basic mechanisms underlying living phenomena are not really understood. Unequivocal interpretations of data concerning the following phenomena--to name but a few--are missing: cellular accumulation of potassium; cellular exclusion of sodium, cell volume regulation, shape change of cells (e.g. of muscle cells during contraction), electrical potential differences between inside and outside of living cells. The theoretical treatment of these phenomena as found in all current textbooks is based on the membrane-pump theory (MPT) with the following essential features. The bulk of the main cellular cation K+ is freely dissolved in free cellular water and membrane-situated pumps are responsible for the high level of K+ and the low level of Na+ found in virtually all living cells. On the other hand, the above mentioned phenomena are explained by the association induction hypothesis (AIH) without the proposal of membrane-situated pumps and with the postulations of selective K+ adsorption to cellular proteins and of a specific cell water structure which has a low solvency for Na+ and other solutes. Experimental findings are reviewed which contradict the MPT and support the AIH. In addition, electron microscopic experiments with cryoprocessed striated muscle are reviewed which establish cellular K+ binding (adsorption) and a cellular water structure which is different from that of normal free water. Cryoexperiments with the striated muscle and model systems are proposed which may help to obtain further information on the specific interactions between proteins, ions, and water in living cells. PMID- 11758732 TI - Thermal properties of hornet colonies: thermography of individual hornets and their nests and the role of the pupal silk in thermoregulation. AB - The present study focused on temperature assessments within a hornet nest. The measurements encompassed adult hornets, brood combs and the various stages of brood, and involved a thermographic method. Body parts of adult hornets were found to vary in their temperature, with the thorax eliciting the highest temperature and the abdomen the lowest. Similarly, there were thermal variances between larvae at instars 4-5, light-colored pupae and dark pupae. The measurements were made at day and night (when the entire population was present in the nest) on nests containing thousands of individuals at various ages. Most of the pupae measured during October were hornet drones. The usual air temperature between the (subterranean) combs was 28.7 degrees C, while the outside (ground level) temperature was 23.5 degrees C. The paper discusses the creation of heat by hornets, the thermoregulation throughout night and day, both by the hornets proper as well as by their products (comb and silk). Also discussed is the intra-nest conversion of one form of energy to another, as heat to electric current or vice versa. PMID- 11758733 TI - Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C deficient ODS rats. AB - Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased. PMID- 11758734 TI - Induction of radio-adaptive response in colony formation by low dose X-ray irradiation. AB - In this study, we examined the induction of a radio-adaptive response to cell death using a colony formation test in m5S, G401.2/6TG.1 and HeLa cells. When m5S cells were subjected to priming irradiation of 0.05 to approximately 0.15 Gy 4 hr before being irradiated with 4.5 Gy, the survival ratios increased significantly to 39 to approximately 42%. The priming irradiation effect was also observed when G401.2/6TG.1 cells were subjected to priming irradiation of 0.025 to approximately 0.1 Gy 4 hr before being irradiated with 0.8 Gy. This effect showed a two-phasic characteristic, where the first peak was reached at 0.025 Gy, and the second peak was reached at 0.075 Gy. The first peak showed a survival ratio of 56%, while the second peak was at 55%. However, in HeLa cells, this priming irradiation effect was not observed. These results indicated that induction of the radio-adaptive response did not depend on whether cells are normal or cancerous. One of the differences in these cells is that m5S and G401.2/6TG.1 cells have gap-junctional intercellular communication, but HeLa cells do not. Induction of the radio-adaptive response may be related to gap-junctional intercellular communication. PMID- 11758735 TI - Novel method to correct displacement profile images and calculate flow vector fields using saturation-tagging MR imaging. AB - Saturation-tagging Magnetic Resonance (MR) imaging provides a simple and robust means to directly visualize displacement profiles within fluid flow fields. Although useful for velocity quantitation as well as for qualitative depiction of flow patterns in certain well-defined flow fields, the technique is prone to distortions due to oblique flow (misregistration artifact) and ambiguity of fluid vector trajectories in complex flow situations. A novel method is proposed whereby two images are acquired, differing in the temporal position of the phase encoding gradient. Theoretical analysis shows that from the paired images, distortion of the two-dimensional displacement profile can be corrected and fluid velocity vectors extracted, even if the flow directions are unknown. In the simpler case of flow oblique to the gradient principal axes, but with a known trajectory, only one image is necessary to correct the displacement profile distortion and extract the velocity information. MRI experiments in a straight tube model have been carried out to evaluate the feasibility of this method. Good agreement is achieved between the results from MR imaging and those predicted via computer simulation. PMID- 11758736 TI - Glucose tolerance and insulin action in monosodium glutamate (MSG) obese exercise trained rats. AB - The present study was designed to evaluate the effects of chronic aerobic exercise (swimming, 1h/day, 5 days/week, with an overload of 5% body weight) on glucose metabolism in obese male Wistar rats. Hypothalamic obesity was induced through administration of monosodium glutamate (MSG) at 4 mg/g of body weight every other day from birth to 14 days old. Fourteen weeks after drug administration, the rats were separated into two groups: MSG-S (sedentary) and MSG-T (swimming for 10 weeks). Rats of the same age and strain, receiving saline in place of MSG, were used as control (C), and subdivided into two groups: C-S and C-T. At the end of the experimental period, an oral glucose tolerance test was performed and serum glucose (AG) and insulin (AI) were evaluated. A constant for serum glucose decrease (Kitt) in response to exogenous insulin was calculated. Soleus muscle strips and adipose tissue samples were incubated and insulin stimulated glucose uptake determined. No differences were observed in AG among the 4 groups. MSG-S rats showed higher Al (418%) and lower Kitt (92.3%) than C-S rats. T-rats showed higher glucose uptake by muscle (224.0%) and adipose tissues (94.1%) than S-rats. Among trained rats, glucose uptake by muscle was higher in MSG-T (5.4%) than in C-T, while the opposite was observed in adipose tissue (39% higher in C-T). Chronic aerobic exercise was able to improve glucose tolerance and reduce insulin resistance in MSG-obese rats. These effects were associated to an increase in glucose uptake by muscle and adipose tissue in response to insulin. PMID- 11758737 TI - Protein deficiency attenuates the effects of alloxan on insulin secretion and glucose homeostasis in rats. AB - We have investigated the effect of alloxan on insulin secretion and glucose homeostasis in rats maintained on a 17% protein (normal protein, NP) or 6% protein (low protein, LP) diet from weaning (21 days old) to adulthood (90 days old). The incidence of alloxan diabetes was higher in the NP (3.5 times) than in the LP group. During an oral glucose tolerance test, the area under serum glucose curve was lower in LP (57%) than in NP rats while there were no differences between the two groups in the area under serum insulin curve. The serum glucose disappearance rate (Kitt) after exogenous insulin administration was higher in LP (50%) than in NP rats. In pancreatic islets isolated from rats not injected with alloxan, acute exposure to alloxan (0.05 mmol/L) reduced the glucose- or arginine stimulated insulin secretion of NP islets by 78% and 56%, respectively, whereas for islets from LP rats, the reduction was 47% and 17% in the presence of glucose and arginine, respectively. Alloxan treatment reduced the glucose oxidation in islets from LP rats to a lesser extent than in NP islets (23% vs. 56%). In conclusion, alloxan was less effective in producing hyperglycemia in rats fed a low protein diet than in normal diet rats. This effect is attributable to an increased peripheral sensivity to insulin in addition to a better preservation of glucose oxidation and insulin secretion in islets from rats fed a low protein diet. PMID- 11758738 TI - Hypothesis on radar sensing and communication by hornets: comments on their antennal organulles and electrical activity. AB - Our study shows that the antenna of the hornet is densely covered from base to tip with six types of organulles, namely, a trichoid organulle, about 23 microm in length, a campaniform organulle which is 12 microm long, a heretofore undescribed structure measuring about 9 microm in length which we have now named the Agmon organulle, a rather flattened placoid organulle measuring about 25 microm in length and not projecting on the antennal surface, and finally rounded structures about 3 microm in diameter which are indented in the cuticle and resemble extraretinal photoreceptors. All the above-mentioned structures occur in the workers and drones, and the latter also possess an additional structure, namely, the tyloid which is about 254 microm long. Such organulles as protrude from the antennal surface are mostly orientated distally and their length is about half that of similar organulles on the hornets body. Yet their density on the antenna is greater than elsewhere on the body and in fact on all the antennal segments (12 in the workers and 13 in the drones) the entire surface area seems to be occupied by them. The most numerous are the trichoids, while the other organulles mentioned are fewer in number. In measuring the electric properties of the antennae, we obtained the following values: 10-80 nanoAmpers (nA), 60-100 milliVolt (mV) and several scores of Mega Ohms (Momega) in the dark, as compared to 10-20 nA, 150-200 mV and few Momega under illumination. We found that in many respects, the cuticle in the antenna behaves like an organic semiconductor possessing thermophotovoltaic (TPV) properties. Apart from contemplating that the role of the antennal organulles is as a mechanoreceptor, a chemoreceptor or a combination of the two, we also raise the conjecture that these organulles might serve as elements that pick up and broadcast at submillimetric wavelengths, and that the electric energy extant in the vespan antennae supplies the energy source for this kind of activity. PMID- 11758739 TI - Metrics of separation in chromatography. AB - A new metric, separation measure, S, for chromatographic separation is proposed. Unlike other metrics such as resolution, separation number, and some versions of peak capacity, the new metric provides a consistent, additive measure of the separation of pairs of peaks as well as the separation capacities of arbitrary intervals within the analysis time. The attribute of additivity means that the separation measure of any separation interval is equal to the sum of the separation measures of its subintervals. Practical aspects of the measurement of S are also addressed. In addition to definition of S, a definition of peak capacity, n, that is consistent with S, and includes useful features of other known definitions of n is proposed for an arbitrary time interval. PMID- 11758740 TI - Prevention of water vapour adsorption by carbon molecular sieves in sampling humid gases. AB - The water uptake by the solid sorbents Carbosieve S-III, Carboxen 569, 1000 and 1001, all of which are used for sampling of volatile organic compounds from the atmosphere. was examined using a direct experimental approach. The content of retained water is affected both by the trap temperature and the initial water vapour concentration in the sampled gas. Two different adsorption mechanism are operative. At low relative humidities (RH) only active polar centres are involved. This adsorption is so weak that negative water interferences can easily be managed. Another mechanism, the micropore volume filling, involves substantial amounts of water, becomes operative once the threshold value for relative humidity (RHth) is surpassed. RHth is 45+/-3% for Carboxen 1000 decreasing to 35+/-3% for the three other sorbents studied. A novel but simple strategy was tested for water management: moderate heating of the trap during the sampling (a warm trap method). The temperature elevation required depends on the RHth characteristic for the specific sorbent, and RH and the temperature of the sampled gas. Usually the 5-15 degrees C elevation is sufficient; only under extreme RH conditions is an elevation of 20 degrees C necessary. The diagrams are given to determine this elevation. Since the sample RH is significantly decreased at an elevated temperature the negative effect of water uptake on the safe sampling volume is alleviated. Consequently the sampled gas volume can be as large as desired which decreases detection limits. PMID- 11758741 TI - Comparison and evaluation of copper complex-containing siloxane polymers as stationary phases for capillary gas chromatography. AB - Two metallomesogenic polymers. P-C11CuC18 and P-C11CuC12 consisting of flexible aliphatic side chains with copper carboxylate complexes have been synthesized on the basis of addition reactions with polysiloxane. The applicability of the prepared columns to the analysis of phthalate esters that are of environmental concern was assessed. For preparation of the capillary column with its wall coated with the metallomesogenic polymer, both static and dynamic methods were employed. Factors affecting the retention and the sample selectivity on both columns were examined. A better separation of phthalates was achieved with P C11CuC18 than P-C11CuC12. The former phase showed a higher solute-solvent interaction than the latter. With static coating, the wall-coated P-C11CuC18 capillary column (15 m x 250 microm I.D.) showed that the baseline separation of all 14 phthalates could be achieved within 38 min with high reproducibility. The calibration graphs for phthalate ester determination were linear over the range of 10-625 microg ml(-1). The mass detection limits were lower than the ng range based on three times the standard deviation of seven measurements of the lowest peak that could be detected. PMID- 11758742 TI - Identification and quantification of natural isoxazolinone compounds by capillary zone electrophoresis. AB - A capillary zone electrophoresis (CZE) method that is specific, simple, rapid and also cheap was developed to analyse some natural UV-absorbing isoxazolinone compounds with toxic potential present in legume seedlings. The six most common natural isoxazolinone compounds were separated within 10 min with 25 mM potassium phosphate (pH 7.5) containing 8% 1-propanol as running buffer. A 60 cm coated fused-silica capillary (52.6 cm effective length x 75 microm I.D.), with an electric field of 375 V/cm at 30 degrees C was used. The limit of detection ranged from 0.01 mM (3.0 microg/ml) to 0.03 mM (7.7 microg/ml). Linearity between peak areas and concentrations ranging from 0.05 mM to 1.75 mM were determined for each isoxazolinone. The correlation coefficient was 0.9954 or greater. Both relative migration time and peak area were reproducible. The RSD of relative migration time is between 0.44 and 1.94% and RSD of peak area is between 1.26 and 6.86%. The concentrations of isoxazolinones in Lathyrus odoratus and L. sativus seedlings obtained by CZE were in agreement with the previous results from HPLC. PMID- 11758743 TI - Quantitative comparison of performance of isothermal and temperature-programmed gas chromatography. AB - As a basic metric of separation for comparing isothermal and temperature programmed GC (gas chromatography), we used the separation measure. S (defined elsewhere). We used this metric as both a measure of separation of any two peaks, and a measure of separation capacity of arbitrary intervals where peaks can potentially exist. We derived several formulae for calculation of S for any pair of peaks regardless of their shape and the distance from each other in isothermal and temperature-programmed GC. The formulae for isothermal GC can be viewed as generalizations of previously known expressions while, in the case of temperature programmed GC, no equivalents for the new formulae were previously known from the literature. In all formulae for S. we identified similar key component-metrics (solute separability, intrinsic efficiency of separation, specific separation measure, separation power) that helped us to identify and better understand the key factors affecting the separation process. These metrics also facilitated the quantitative comparison of separation capacities and analysis times in isothermal and temperature-programmed GC. Some of these metrics can be useful beyond GC. In the case of GC, we have shown that, if the same complex mixture was analyzed by the same column, and the same separation requirements were used then isothermal analysis can separate more peaks than its temperature-programmed counterpart can. Unfortunately, this advantage comes at the cost of prohibitively longer isothermal analysis time. The latter is a well know fact. Here, however, we provided a quantitative comparison. In a specific example, we have shown that a single-ramp temperature program with a typical heating rate yields about 25% fewer peaks than the number of peaks available from isothermal analysis of the same mixture using the same column. However, that isothermal analysis would last 1000 times longer than its temperature-programmed counterpart. Using twice as longer column in the case of a temperature-programmed analysis, allows one to recover the 25% disadvantage in the number of separated peaks, while still retaining a 500-fold advantage in the speed of analysis. PMID- 11758744 TI - Monofluorinated polycyclic aromatic hydrocarbons as internal standards to monitor trace enrichment and desorption of their parent compounds during solid-phase extraction. AB - Solid-phase extraction (SPE) is an established sample-preparation technique for clean-up procedures of polycyclic aromatic hydrocarbons (PAHs). The suitability of monofluorinated polycyclic aromatic hydrocarbons (F-PAHs) as a novel set of internal standards, was tested for two widely used SPE sorbents, octyl-bonded silica and styrene-divinylbenzene copolymer. The elution profiles of eight F-PAHs and their parent PAHs, taken from the priority pollutant list of the US Environmental Protection Agency, were compared for demineralized water and waste water. In both instances, the match of the elution profiles was exceptionally close. The eight F-PAHs and the corresponding PAHs were determined by reversed phase liquid chromatography using acetonitrile-water gradient elution with UV detection at 254 nm. The UV spectra of the F-PAHs show a small bathochromic shift compared with the parent PAHs. PMID- 11758745 TI - Pressurized liquid extraction for the determination of polyphenols in apple. AB - Pressurized liquid extraction (PLE) has been optimized for the determination of polyphenols in Golden Delicious apple peel and pulp. The effects of experimental variables, such as solvent composition, temperature, static extraction time and pressure, on PLE efficiency have been studied. Once the optimum conditions were established the recovery and the precision of the method for each analyte was tested by means of repeated analysis. PMID- 11758746 TI - Prediction of retention behaviour and evaluation of pka values of peptides and quinolones in liquid chromatography. AB - The present paper examines the effect of the solute ionisation on the retention behaviour in liquid chromatography of a series of peptide and quinolone compounds of biological interest, using acetonitrile-water media as mobile phases and a polymeric-based stationary phase. Polymeric columns with polystyrene divinylbenzene (PS-DVB) polymer show advantages over silica-based reversed-phase packings since the former are stable in a wide pH range. (s)(s)pKa values have been evaluated using chromatographic data in acetonitrile-water mixtures with acetonitrile percentages of 30, 35, 40 and 50% (v/v) for quinolones and 12.5 and 20% (v/v) for peptides. The quinolones show great retention on PS-DVB phase stationary. It was thus necessary to work with a higher acetonitrile content in the mobile phase than for the less retained peptides. The pH values were measured in the hydroorganic mixtures, used as mobile phases, instead of in water and account was taken of the effect of activity coefficients. The derived equations permit the chromatographic determination of (s)(s)pKa. values of the peptides and quinolones in acetonitrile-water mixtures by fitting it to the experimental data in a nonlinear least-square procedure and also permit the prediction of the effect of (s)(s)pH on their chromatographic behaviour. We have also compared the obtained (s)(s)pKa values with those previously obtained in acetonitrile-water mixtures from potentiometric measurements. PMID- 11758747 TI - Determinants of protein retention characteristics on cation-exchange adsorbents. AB - There are currently a large number of commercially available strong and weak cation-exchange adsorbents for preparative protein purification, typically prepared by coupling charged ligands to a mechanically rigid porous bead. Because of the diverse chemical nature of the base matrix (carbohydrate, synthetic polymer, inorganic) and the coupling and ligand chemistry, cation-exchange adsorbents from different suppliers can differ substantially in chemical surface properties and physical structure. The differences in chemical properties can be in ionic capacity, hydrophobicity, the presence of hydrogen bond donors/acceptors, and the nature of the charged functional groups. In order to probe the effects of these factors on protein affinity, the isocratic retention of a set of model proteins was examined on a set of cation-exchange adsorbents to obtain a quantitative assessment of retention differences between adsorbents. Two adsorbent factors were found to be the dominant determinants of overall protein retention: the anion type and the adsorbent pore size distribution. Protein retention on strong cation-exchangers was found to be greater than that on corresponding weak cation-exchangers. Protein retention was increased on adsorbents with pore size distributions that include significant amounts of pore space with dimensions similar to those of the protein solute. PMID- 11758748 TI - Unique selectivity of perfluorinated stationary phases with 2,2,2 trifluoroethanol as organic mobile phase modifier. AB - The selectivity of Luna C18 Xterra C18 and Fluophase (perfluorinated C6) stationary phases has been investigated with aqueous acetonitrile, methanol and 2,2,2-trifluoroethanol mobile phases using linear solvation equations. The gradient retention times of a set of 60 compounds with known molecular descriptors have been determined. Linear solvation equations have been set up to describe the relationship between the gradient retention times and the molecular properties. The selectivity of the stationary phase/mobile phase systems was characterised by the regression coefficients of the molecular descriptors. The perfluorinated stationary phase showed very different selectivity using 2,2,2 trifluoroethanol (TFE) as co-solvent. Compounds with H-bond donor functionality were retained much less than in the other investigated high-performance liquid chromatography (HPLC) systems. This unique selectivity can be explained by the stronger adsorption of trifluoroethanol on the perfluorinated stationary phase surface, than on the hydrocarbon surface. It suggests the importance of the adsorbed organic modifiers in the separation mechanism during reversed-phase HPLC. PMID- 11758749 TI - Impact of triethylamine as a mobile phase additive on the resolution of racemic amino acids on an (+)-18-crown-6-tetracarboxylic acid-derived chiral stationary phase. AB - Recently, a new HPLC chiral stationary phase (CSP) prepared by covalently bonding (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid on silica gel was successfully employed in resolving various racemic natural and unnatural amino acids containing a primary amino group. Current work details on-going efforts to improve the effectiveness of this type of material. The analytes used in this study included various substituted phenylalanines, phenylglycine homologues and other primary amino acids. In an attempt to increase enantioselectivity, the effect of methanol and triethylamine modifiers was evaluated in an aqueous mobile phase containing sulfuric acid. In general. retention time increased with increasing methanol and triethylamine concentration. In addition, highest enantioselectivities were obtained with high methanol and high triethylamine; however, these conditions produced excessively long retention. All of the analytes were well resolved on the CSP with a mobile phase of 20% methanol containing 14.3 mM triethylamine and 10.0 mM sulfuric acid. PMID- 11758750 TI - Quantitative determination of aflatoxin B1-oxime by column liquid chromatography with ultraviolet detection. AB - Liquid chromatography was used for the quantification of aflatoxin B1-oxime (AFB1 oxime). The yield of AFB1-oxime in the reaction mixture was 89%, while after purification on silica gel it was 72%. LC analysis of the reaction mixture after silica gel fractionation revealed a retention time of 0.84 min for AFB1-oxime, 8.42 min for AFB1, 1.21 min for unknown 1 and 1.61 min for unknown 2. UV-visible analysis of the reaction mixture after silica gel fractionation showed a lambda(max) of 269 and 361 nm for AFB1-oxime, 263 and 360 nm for AFB1, 273 nm for unknown 1 and 275 nm for unknown 2. Excitation and emission wavelengths were found to be 269 and 368/438 nm for AFB1-oxime, 359/424 nm for AFB1, 270 and 367/450 nm for unknown 1 and 273 and 416/447 nm for unknown 2. The method may find versatile application in monitoring reactions for the preparation of oximes of various analytes for the synthesis of their immunogens. PMID- 11758751 TI - Chiral separation of 9-fluorenylmethyl chloroformate- and dansyl chloride derivatized D,L-serine by gamma-cyclodextrin-bonded high-performance liquid chromatography. AB - When acetate buffer was used in chiral separation of D,L-serine derivatives using a gamma-cyclodextrin (CD) column, both retention factor and resolution were high below the pKa of acetic acid and decreased sharply as the pH approached the pKa. A similar result was obtained by increasing the buffer concentration at a fixed pH. These observations suggest that hydrogen bonding interaction between the carboxylate group of the amino acid and the secondary hydroxyl groups at the CD rim plays an important role in chiral separation and is disrupted by the buffer anion. PMID- 11758752 TI - Additional transporter characterization may lead to new pharmaceutical opportunities. PMID- 11758753 TI - Diamonds in the rough: protein crystals from a formulation perspective. AB - The focus of the present review is to address the use of protein crystals in formulation design. Although this idea has been present for some time, i.e., insulin crystals were first reported back in 1920s, macromolecular crystallization has not received as much attention as the other methods for stabilizing protein drug candidates. The prospective potential of crystalline protein formulations in light of new advances in the field of macromolecular crystallization was reviewed, and the basic concepts and the tools now available for developing protein crystals into drug formulations are introduced. In addition, formulation challenges and regulatory demands, along with examples of current applications of protein crystals, are presented. PMID- 11758754 TI - Distribution and diffusion of sodium taurocholate and egg phosphatidylcholine aggregates in rat intestinal mucin. AB - PURPOSE: The permeability of rat intestinal mucin (RIM) to sodium taurocholate/egg phosphatidylcholine (TC/PC)-mixed micelles has been investigated. METHODS: The time dependence for the equilibration of TC/PC-mixed lipid micelles with isolated RIM was determined. Thereafter the distribution of TC/PC-mixed lipid micelles was assessed at low and high PC and intermicellar concentrations (IMC) and with different RIM concentrations. The equilibrium distribution of PC and TC was determined by analysis for phosphorus and by high performance liquid chromatography, respectively, as well as by nuclear magnetic resonance spectroscopy. In addition, the diffusion coefficients of water, PC, and TC were measured by pulsed field gradient nuclear magnetic resonance spectroscopy. Two model solutes, phenylmethyltrimethylsilane (PTMS) and tetramethylsilyl-tetradeutero-proprionic acid (TSP), were added to the high PC, low IMC samples, and the diffusion coefficients were determined. RESULTS: The time to reach equilibrium was 2 days for a system with a high intermicellar concentration of sodium taurocholate. At low PC concentrations, RIM had slightly higher PC concentrations relative to the control. In contrast, at high PC concentrations, RIM samples had lower PC concentrations. The concentration of TC was largely independent of mucin concentration. The water diffusivity was reduced proportionately to the concentration of RIM, and analysis indicated that about 150 g of water moved as a kinetic unit with each gram of mucin. The diffusion coefficients of PC were also reduced with increasing RIM concentration. The magnetization decay of TC did not always follow a monoexponential decay, reflecting the simultaneous diffusion and exchange among sites imparting different relaxation behavior on the TC. Magnetization decay curves were simulated and the diffusivity of TC in mucin was estimated. The diffusion coefficient of TSP was 10 times larger than that of PTMS in the presence of micelles and mucin. CONCLUSIONS: RIM is highly hydrated, and dilute solutions have a minor exclusive effect on the high concentration of PC/TC micelles. At low concentrations of PC, there appears to be preferential association of the PC with the RIM. The permeability of mucin to solutes in the presence of bile salt mixed micelles critically depends on the degree of association of the solute with the micelle. PMID- 11758755 TI - Predicted permeability of the cornea to topical drugs. AB - PURPOSE: To develop a theoretical model to predict the passive, steady-state permeability of cornea and its component layers (epithelium, stroma, and endothelium) as a function of drug size and distribution coefficient (phi). The parameters of the model should represent physical properties that can be independently estimated and have physically interpretable meaning. METHODS: A model was developed to predict corneal permeability using 1) a newly developed composite porous-medium approach to model transport through the transcellular and paracellular pathways across the epithelium and endothelium and 2) previous work on modeling corneal stroma using a fiber-matrix approach. RESULTS: The model, which predicts corneal permeability for molecules having a broad range of size and lipophilicity, was validated by comparison with over 150 different experimental data points and showed agreement with a mean absolute fractional error of 2.43, which is within the confidence interval of the data. In addition to overall corneal permeability, the model permitted independent analysis of transcellular and paracellular pathways in epithelium, stroma and endothelium. This yielded strategies to enhance corneal permeability by targeting epithelial paracellular pathways for hydrophilic compounds (phi < 0.1 - 1), epithelial transcellular pathways for intermediate compounds, and stromal pathways for hydrophobic compounds (phi > 10 - 100). The effects of changing corneal physical properties (e.g., to mimic disease states or animals models) were also examined. CONCLUSIONS: A model based on physicochemical properties of the cornea and drug molecules can be broadly applied to predict corneal permeability and suggest strategies to enhance that permeability. PMID- 11758756 TI - Lontophoretic delivery of apomorphine in vitro: physicochemic considerations. AB - PURPOSE: To examine the mechanisms of transdermal iontophoretic delivery of apomorphine. METHODS: Anodal iontophoresis of R-apomorphine across human stratum corneum was determined in vitro. The effects on the flux of the following parameters were studied: stability of drug, pH of donor solution, concentration of NaCl, and type of Na+ co-ions. RESULTS: Ascorbic acid was effective to prevent apomorphine degradation. The iontophoretic transport of apomorphine was strongly influenced by the pH of the donor formulation. Increasing the pH from 3 to 6 resulted in an increase in the iontophoretic apomorphine flux from 27.9+/-4.4 nmol/cm2*h to 78.2+/-6.9 nmol/cm2*h. Upon decreasing NaCl concentration from 8 to 2 g/L, the iontophoretic flux was not significantly changed. Replacing NaCl in the donor formulation by tetraethylammonium chloride or tetrabutylammonium chloride resulted in 1.3 fold greater steady-state flux. CONCLUSIONS: For optimized apomorphine iontophoretic delivery, a constant pH of the donor formulation is of great importance. The results suggest that although flux enhancement during iontophoresis is largely due to the electrical potential gradient, secondary effects, such as convective flow and electroosmosis may also contribute. PMID- 11758757 TI - Intracellular drug delivery using low-frequency ultrasound: quantification of molecular uptake and cell viability. AB - PURPOSE: To determine the dependence on acoustic parameters of molecular uptake and viability of cells exposed to low-frequency ultrasound. METHODS: DU145 prostate cancer cells bathed in a solution of calcein were exposed to ultrasound at 24 kHz over a range of different acoustic pressures. exposure times, pulse lengths, and duty cycles. Flow cytometry was employed to quantify the number of calcein molecules delivered into each cell and levels of cell viability. RESULTS: Both molecular uptake and cell viability showed a strong dependence on acoustic pressure and exposure time, weak dependence on pulse length, and no significant dependence on duty cycle. When all of the data were pooled together, they exhibited good correlation with acoustic energy exposure. Although molecular uptake showed large cell-to-cell heterogeneity, up to approximately 15% of cells achieved an intracellular calcein concentration approximately equal to its extracellular concentration. CONCLUSIONS: Large numbers of molecules can be delivered intracellularly using low-frequency ultrasound. Both uptake and viability correlate with acoustic energy, which is useful for design and control of ultrasound protocols. PMID- 11758758 TI - Gliadin nanoparticles as carriers for the oral administration of lipophilic drugs. Relationships between bioadhesion and pharmacokinetics. AB - PURPOSE: The aim of this work was to evaluate the bioadhesive properties of non hardened gliadin nanoparticles (NPs) and cross-linked gliadin nanoparticles (CL NP) in the carbazole pharmacokinetic parameters obtained after the oral administration of these carriers. METHODS: A deconvolution model was used to estimate the carbazole absorption when loaded in the different gliadin nanoparticles. In addition, the elimination rates of both adhered and non-adhered nanoparticulate fractions within the stomach were estimated. RESULTS: Nanoparticles dramatically increased the carbazole oral bioavailability up to 49% and provided sustained release properties related to a decrease of the carbazole plasma elimination rate. The carbazole release rates from nanoparticles (NP and CL-NP), calculated by deconvolution, were found to be of the same order as the elimination rates of the adhered fractions of nanoparticles in the stomach mucosa. In addition, good correlation was found between the carbazole plasmatic levels, during the period of time in which the absorption process prevails, and the amount of adhered carriers to the stomach mucosa. CONCLUSION: Gliadin nanoparticles significantly increased the carbazole bioavailability, providing sustained plasma concentrations of this lipophilic molecule. These pharmacokinetic modifications were directly related to the bioadhesive capacity of these carriers with the stomach mucosa. PMID- 11758759 TI - Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. AB - PURPOSE: This study was performed to determine the detailed mRNA distribution of organic cation transporters, rOCT1 and rOCT2, along the rat nephron and to distinguish the substrate affinities of these transporters. METHODS: The distributions of rOCT1 and rOCT2 mRNA were determined by reverse transcriptase polymerase chain reaction analysis of microdissected nephron segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inhibitory effects of various compounds on the uptake of [14C]tetraethylammonium were assessed. RESULTS: rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight and convoluted tubules, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic drugs and endogenous cations on [14C]tetraethylammonium uptake across the basolateral membranes in the transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specificity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4 phenylpyridinium, dopamine, disopyramide, and chlorpheniramine. CONCLUSIONS: rOCT1 and rOCT2 possess similar but not identical multispecificities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic roles in the renal handling of cationic compounds. PMID- 11758761 TI - Effect of probenecid on fluorescein transport in the central nervous system using in vitro and in vivo models. AB - PURPOSE: The purpose of this study was to characterize the function of multidrug resistance-associated proteins (MRPs) (or MRP-like organic anion transport systems) in the blood-brain harrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) using both an in vitro BBB model and an in vivo microdialysis model. METHODS: In vitro functional studies were performed using bovine brain microvessel endothelial cells (BBMEC). The accumulation of fluorescein, an anionic fluorescent dye, in BBMEC was determined with and without the presence of inhibitors of various efflux transport proteins. In vivo microdialysis simultaneously monitored fluorescein concentrations in cortical extracellular fluid and cerebrospinal fluid. The effect of probenecid on the in vivo distribution of fluorescein was studied using a balanced crossover design in the rat. RESULTS: In vitro experiments showed that probenecid, indomethacin, LY 329146, and all MRP inhibitors significantly increased (two- to threefold) the accumulation of fluorescein in BBMEC, whereas LY-335979, a P-gp inhibitor, had no effect on the accumulation of fluorescein. Probenecid significantly increased fluorescein plasma concentration and the plasma free fraction in vivo. The distribution of fluorescein across the BBB and BCSFB was enhanced by 2.2- and 1.9 fold, respectively, when probenecid was coadministered, even after correction for increased fluorescein plasma concentrations and free fraction. CONCLUSIONS: These results demonstrate that MRPs or MRP-like transport system(s) may play an important role in fluorescein distribution across both BBB and BCSFB. This study showed that microdialysis proved to be a powerful in vivo technique for the study of transport systems in the central nervous system, and in vitro/in vivo correlations are possible using these model systems. PMID- 11758760 TI - Influence of P-glycoprotein modulators on cardiac uptake, metabolism, and effects of idarubicin. AB - PURPOSE: The clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought to determine the influence of P-gp inhibitors verapamil and PSC 833 on myocardial uptake, metabolism, and actions of IDA. METHODS: In Langendorff-perfused rat hearts, the outflow concentration-time curve and the residual amount in cardiac tissue of IDA and its active metabolite idarubicinol (IDOL) were measured after 0.5 mg dose of IDA in the absence and presence of the P-gp inhibitors verapamil and PSC 833. RESULTS: During perfusion (80 min), 2% of the IDA dose was converted to IDOL in the heart. Myocardial uptake of IDA was significantly increased by verapamil but not by PSC 833, which increased the recovery of IDA and IDOL. IDA significantly decreased left ventricular developed pressure to approximately 40% and increased coronary vascular resistance to 140% of baseline level, respectively. The vasoconstrictive effect was markedly potentiated by PSC 833. CONCLUSIONS: The enhancement of myocardial IDA uptake by verapamil could be due to a decrease in P-gp-mediated efflux. PSC 833 inhibits cardiac metabolism (non IDOL pathways) and increases the acute cardiotoxicity of IDA. PMID- 11758762 TI - The cellular uptake and metabolism of clodronate in RAW 264 macrophages. AB - PURPOSE: Non-nitrogen-containing bisphosphonates, such as clodronate (dichloromethylene bisphosphonate), appear to act as prodrugs, their active form being the AppCp-type analogues of ATP. To further elucidate this, we examined the cellular uptake of clodronate and intracellular accumulation of the metabolite of clodronate (AppCCl2p) in RAW 264 macrophages, the influence of clodronate metabolism on the intracellular ATP concentration, and the time course of clodronate metabolism and the effects of clodronate on cytokine secretion from macrophages. METHODS: The cellular uptake of clodronate was measured using 14C labeled clodronate. AppCCl2p was determined in cell extracts by using an ion pairing HPLC-ESI-MS. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay. Intracellular ATP concentration was measured with a luminometer using a luciferin-luciferase assay. RESULTS: Of the clodronate internalized by macrophages in vitro, 30-55% is metabolized to AppCCl2p, which accumulates to high intracellular concentrations during the first 12 h of exposure. This accumulation does not affect the ATP levels in the cells. The time course of metabolite appearance in the cells and the inhibition of cytokine secretion were very similar. CONCLUSIONS: These results strongly support the idea that clodronate acts as a prodrug, the active form being its intracellular AppCCl2p metabolite. PMID- 11758763 TI - Liquid dose pulmonary instillation of gentamicin PulmoSpheres formulations: tissue distribution and pharmacokinetics in rabbits. AB - PURPOSE: To assess the pharmacokinetics and biodistribution of gentamicin, delivered as PulmoSpheres formulations in rabbit serum and lung tissue following intratracheal instillation in a perflubron vehicle. METHODS: Rabbits were anesthetized, intubated, and mechanically ventilated with O2 (FiO2 = 0.50). Animals were then given 5 mg/kg gentamicin either intravenously, intramuscularly (TM), or intratracheally (IT) gentamicin PulmoSpheres formulation, instilled in 1.8 ml/kg of liquid perflubron vehicle. Serum and lung lobe sections were collected at multiple time points and assayed for gentamicin content. RESULTS: Serum gentamicin levels peaked at 64.7 microg/ml, 11.2 microg/ml, and 5.0 microg/ml following intravenous, TM, and IT administration, respectively. Absolute bioavailabilitv at 8 h for IM administration was 76.8% and 57.0% when delivered IT. Although peak lung levels of drug were reached within 1 h, total lung gentamicin concentration after IT administration was more than two orders of magnitude greater than that achieved following TM administration (680,540 vs. 4,985 microg min, respectively) with significant levels of the antibiotic remaining in the lung even after 1 week. CONCLUSIONS: High levels of gentamicin in lung tissue can be achieved by instillation of a gentamicin PulmoSpheres formulation in a perflubron vehicle, termed liquid dose installation, without reaching toxic systemic levels allowing for increased local delivery of agents such as gentamicin at the site of the infection. PMID- 11758764 TI - Microcrystalline cellulose-water interaction--a novel approach using thermoporosimetry. AB - PURPOSE: To study the physical state of water in microcrystalline cellulose (MCC) and in silicified microcrystalline cellulose wet masses and the effect of granulation on different water fractions. METHODS: Thermoporosimetry, together with the solute exclusion technique, was used to measure different water fractions and pore size distributions of wet granules. To understand the effect of granulation on the physical state of water, both ungranulated and granulated wet masses were studied. In addition, dynamic and isothermal step melting procedures were compared. RESULTS: Four distinct fractions of water (nonfreezing, freezing bound, free, and bulk water) could be detected in MCC wet masses. Granulation decreased the volume of bulk water and increased the volume of freezing bound and free water. Consequently, granulated wet masses were able to hold more water inside the particles compared to ungranulated wet masses. Thus, granulation had a similar effect on MCC as beating has on cellulose fibers in the papermaking proces CONCLUSIONS: Thermoporosimetry and solute exclusion increased the understanding of MCC-water interaction and showed how the physical state of water in MCC wet masses changes during granulation. PMID- 11758765 TI - Use of solid corrugated particles to enhance powder aerosol performance. AB - PURPOSE: To study the dispersion performance of non-porous corrugated particles, with a focus on the effect of particle surface morphology on aerosolization of bovine serum albumin (BSA) powders. METHODS: The solid-state characteristics of the spray-dried BSA powders, one consisting of smooth spherical particles and another corrugated particles, were characterized by laser diffraction, X-ray powder diffraction, scanning electron microscopy, confocal microscopy, thermogravimetric analysis, surface area analyzer, and buoyancy method. The powders were dispersed using the Rotahaler and the Dinkihaler coupled to a four stage liquid impinger operating at 30 to 120 L/min. Fine particle fraction (FPF) was expressed as the wt. % of BSA particles of size < or =5 microm collected from the liquid impinger. RESULTS: Apart from the morphology and morphology-related properties (specific surface area, envelope density), the corrugated particles and spherical particles of BSA had very similar solid-state characteristics (particle size distribution, water content, true density, amorphous nature). Using the Dinkihaler, the FPFs of the corrugated particles were 10-20 wt. % higher than those of the smooth particles. Similar FPF differences were found for the powders dispersed by the Rotahaler, but the relative changes were larger. In addition, the differences were inversely proportional to the air flows (17.3% at 30 L/min, 25.2% at 60 L/min, 13.8% at 90, 8.5% at 120 L/min). Depending on the inhaler, capsule and device retention and impaction loss at the impinger throat were lower for the corrugated particles. CONCLUSIONS: Enhanced aerosol performance of powders can be obtained by surface modification of the particles. The surface asperities of the corrugated particles could lower the true area of contact between the particles, and thus reduce the powder cohesiveness. A distinct advantage of using corrugated particles is that the inhaler choice and air flow become less critical for these particles. PMID- 11758766 TI - Stabilizing and solubilizing effects of sulfobutyl ether beta-cyclodextrin on prostaglandin E1 analogue. AB - PURPOSE: Parent cyclodextrins are known to accelerate the degradations such as dehydration and isomerization of E-type prostaglandins in neutral and alkaline solutions. The objective of this study was to attempt the stabilization and solubilization of E1-type prostaglandin analogue in aqueous solution by biocompatible cyclodextrin derivatives. METHODS: The interaction of an E1-type prostaglandin, methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-4-(m methoxymethylphenyl)1-butenyl]-5-oxocyclopentyl]-5-thiaheptanoate (MEester) with cyclodextrins (CyDs) was studied by spectroscopies and the solubility method. The degradation of MEester was monitored by high-performance liquid chromatography. RESULTS: 1H-nuclear magnetic resonance spectroscopic studies indicated that MEester forms 1:1 inclusion complexes with alpha-, beta-, and gamma-CyDs in solutions, where alpha-CyD interacts with the a-side chain containing methyl ester moiety of the drug, whereas beta- and gamma-CyDs preferentially include around the five-membered ring and both side chains of the drug. Parent alpha-CyD and hydrophilic derivatives, such as 2-hydoxypropyl-alpha- and -beta-CyDs, sulfobutyl ether beta-CyD (SBE-beta-CyD) and maltosyl beta-CyD showed higher solubilizing abilities against MEester over parent beta- and gamma-CyDs. SBE-beta CyD and 2,6-dimethyl-beta-CyD (DM-beta-CyD) significantly decelerated the degradation of MEester, particularly the base-catalyzed dehydration, in neutral and alkaline solutions, whereas other CyDs accelerated the degradation. The acid catalyzed degradation of MEester (pH < 3) was decelerated by the addition of CyDs, especially alpha-CyD. CONCLUSIONS: SBE-beta-CyD with low hemolytic activity and low toxicity is useful as a pharmaceutical carrier for the preparation of injectable MEester, because of its higher stabilizing and solubilizing effects on MEester. Furthermore, SBE-beta-CyD can be useful as a stabilizing agent for drugs, that are subject to base-catalyzed degradations, probably because of the electric repulsion between anionic charges of the sulfobutyl moiety and catalytic anionic species such as hydroxide ion. PMID- 11758767 TI - Controlled drug release from gels using surfactant aggregates. II. Vesicles formed from mixtures of amphiphilic drugs and oppositely charged surfactants. AB - PURPOSE: The aim of this study was to control the release of charged drugs from gels by adding surfactants that can interact with the drug and polymer matrix. METHODS: The in vitro release from gels was measured by using 6-mL gel holders immersed in 250 mL of simulated tear fluid and detecting the ultraviolet absorbance on-line. Gels were characterized by using a controlled rate rheometer, and surfactant aggregates were characterized by using cryo-transmission electron microscopy. RESULTS: The diffusion coefficient of alprenolol was 2.8 x 10(-6) cm2/s in a lipophilically modified poly(acrylic acid) gel without surfactants present and 0.14 x 10(-6) cm2/s when formulated with 1% sodium dodecyl sulfate. For fluvastatin, the diffusion coefficient changed from 3.0 x 10(-6) cm2/s to 0.07 x 10(-6) cm2/s in the presence of 0.2% benzyldimethyldodecyl-ammonium bromide. Alprenolol, betaxolol, metoprolol, diphenhydramine, and fluvastatin formed vesicles with oppositely charged surfactants in physiologic salt conditions. CONCLUSIONS: In this article we show that it is feasible to control the release of charged drugs from gels by using surfactants. Vesicles are generally formed when surface active drugs are mixed with oppositely charged surfactants in physiologic conditions. The strongest effects on the release rate are seen for lipophilically modified polymer gels in which the drug and the oppositely charged surfactant form vesicles, but systems with micelles also give a slower release. PMID- 11758768 TI - On the release of proteins from degrading dextran methacrylate hydrogels and the correlation with the rheologic properties of the hydrogels. AB - PURPOSE: To study the release of macromolecules of different sizes (bovine serum albumin, immunoglobulin G) from degrading (addition of dextranase) dextran methacrylate (dex-MA) hydrogels and to correlate the release with the evolution of the rehologic properties of the hydrogels during degradation. METHODS: The size of the macromolecules, the degree of substitution (i.e., number of methacrylates per 100 glycopyranose residues) of the dex-MA and the dextranase concentration in the hydrogels was varied. The rheologic properties were measured with a controlled stress rheometer. RESULTS: The release from dex-MA hydrogels without dextranase was very small [7-20% (time frame up to 180 days)] showing that most of the molecules were entrapped within the hydrogel network. The release from degrading dex-MA hydrogels followed zero-order kinetics for all molecules during a substantial period of the release. This was explained by a liberation and an increasing diffusivity of the proteins in the course of the degradation. The total amount released and the release rates could be well correlated with the rheologically observed degradation rates. CONCLUSIONS: It was shown that rheology can be a useful tool to help explain the release from degrading hydrogels. PMID- 11758770 TI - Pharmacokinetics and pharmacodynamics of 7-nitroindazole, a selective nitric oxide synthase inhibitor, in the rat hippocampus. AB - PURPOSE: This study was conducted to assess the pharmacokinetics and pharmacodynamics of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (NOS). METHODS: Male Sprague-Dawley rats were equipped with peritoneal/ venous cannulae and a microdialysis probe in the hippocampal cortex. Rats received 7-NI in peanut oil (25 mg/kg) ip every 2 h for 14 h or peanut oil alone. Blood samples were obtained at timed intervals for serum 7-NI; brain tissue microdialysate for determination of extracellular 7-NI and NO was obtained every 20 min. A pharmacokinetic-pharmacodynamic model was constructed to evaluate the effects of 7-NI on NOS activity. RESULTS: Consistent with previous reports. NOS activity in controls evidenced circadian variation. These cyclic changes in NO production were incorporated into the model of 7-NI effects on NOS. 7-NI produced a rapid (within 2 h) decrease in hippocampal NO. Under the conditions of this experiment, 7-NI produced an approximately 50% decrease in hippocampal NO, which was sustained during 7-NI administration. The decrease in NOS activity by 7 NI was concentration-dependent with an apparent IC50 of approximately 17 microg/ml. CONCLUSIONS: Multiple ip injections of 7-NI result in a predictable, sustained decrease in NO production in the hippocampus. The pharmacokinetic pharmacodynamic model developed allows design of dosing regimens that can produce designated changes in brain NO content, facilitating use of 7-NI to probe the pharmacological implications of NO in the central nervous system. PMID- 11758769 TI - Preparation and characterization of a composite PLGA and poly(acryloyl hydroxyethyl starch) microsphere system for protein delivery. AB - PURPOSE: To prepare and characterize a novel composite microsphere system based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(acryloyl hydroxyethyl starch) (acHES) hydrogel for controlled protein delivery. METHODS: Model proteins, bovine serum albumin, and horseradish peroxidase were encapsulated in the acHES hydrogel, and then the protein-containing acHES hydrogel particles were fabricated in the PLGA matrix by a solvent extraction or evaporation method. The protein-loaded PLGA-acHES composite microspheres were characterized for protein loading efficiency, particle size, and in vitro protein release. Protein stability was examined by size-exclusion chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and monitoring the enzymatic activity. RESULTS: Scanning electron microscopy showed discrete PLGA microspheres containing many acHES particles. The composite microspheres were spherical and smooth in size range of 39-93 microm. The drug loading efficiency ranged from 51 to 101%. The composite microspheres showed more favorable in vitro release than conventional PLGA microspheres. The composite microspheres showed 20% less initial with a gradual sustained release compared to high burst (approximately 60%) followed by a very slow release with the conventional PLGA microspheres. The composite microspheres also stabilized encapsulated proteins from the loss of activity during the microsphere preparation and release. Proteins extracted from the composite microspheres showed good stability without protein degradation products and structural integrity changes in the size-exclusion chromatography and SDS-PAGE analyses. Horseradish peroxidase extracted from microspheres retained more than 81% enzymatic activity. CONCLUSION: The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs. PMID- 11758771 TI - Influence of surface-modifying surfactants on the pharmacokinetic behavior of 14C poly (methylmethacrylate) nanoparticles in experimental tumor models. AB - PURPOSE: The aim of this study was to investigate the different pharmacokinetic behavior of surface-modified poly(methylmethacrylate) (PMMA) nanoparticles. METHODS: The particles were 14C-labeled and coated with polysorbate 80, poloxamer 407, and poloxamine 908. Plain particles served as control particles. In vivo studies were performed in three tumor models differing in growth, localization, and origin. Particle suspensions were administered via the tail vein, and at given time animals were killed and organs were dissected for determination of PMMA concentration. RESULTS: For the PMMA nanoparticles coated with poloxamer 407 or poloxamine 908, high and long-lasting concentrations were observed in the melanoma and at a lower level in the breast cancer model. In an intracerebrally growing glioma xenograft, the lowest concentrations that did not differ between the tumor-loaded and tumor-free hemispheres were measured. Organ distribution of the four investigated batches differed significantly. For instance, poloxamer 407 and poloxamine 908-coated particles circulated over a longer period of time in the blood, leading additionally to a higher tumor accumulation. In contrast, plain and polysorbate 80-coated particles accumulated mainly in the liver. The strong expression of vascular endothelial growth factor and Flk-1 in the melanoma correlated with high concentrations of PMMA in this tumor. CONCLUSION: The degree of accumulation of PMMA nanoparticles in tumors depended on the particle surface properties and the specific growth differences of tumors. PMID- 11758772 TI - Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model. AB - PURPOSE: This study was conducted to explore the role of the peripheral lymphatics in insulin absorption following subcutaneous (SC) administration using a sheep model that allows continuous collection of peripheral lymph and simultaneous assessment of systemic bioavailability. METHODS: In a parallel group design, soluble human insulin (0.5 IU/kg) was administered by bolus SC injection into the interdigital space of the hind leg of non-cannulated control sheep, and sheep in which the efferent popliteal lymph duct was cannulated. A separate group received a bolus IV injection (0.15 IU/kg). Blood was sampled from all animals, and lymph was collected continuously over 12 h postdosing. Samples were assayed for insulin by ELISA. RESULTS: The SC bioavailability of insulin in control sheep was 31.5+/-3.2%, which was significantly higher than when the peripheral lymph was continuously collected (18.4+/-1.7%). In the lymph-cannulated animals, 17.3+/ 1.0% of the dose was collected in peripheral lymph. CONCLUSIONS: Based on the direct measurement of insulin in regional lymph and on the decrease in the systemic bioavailability when regional lymph was continuously collected, the results demonstrate that lymphatic absorption contributed significantly to the overall insulin bioavailability following SC administration to sheep. PMID- 11758773 TI - Effect of elastic liquid-state vesicle on apomorphine iontophoresis transport through human skin in vitro. PMID- 11758774 TI - Inhibition of nuclear transcription factor-kappaB by specific IkappaB kinase peptide inhibitor. PMID- 11758775 TI - Physical and chemical enhancement of transdermal delivery of triptorelin. PMID- 11758776 TI - Enhancement of the intestinal absorption of low molecular weight heparin (LMWH) in rats and pigs using Carbopol 934P. PMID- 11758777 TI - Nitric oxide synthase expression of oligodendrogliomas. AB - In the central nervous system, nitric oxide (NO) has a variety of biological functions including vasorelaxation and neurotransmission. The synthesis of NO is catalyzed by NO synthases (NOS) existing in 3 isoforms, neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO synthase has implications in the pathophysiology of primary glial brain tumors with enhanced expression of nNOS and eNOS in high-grade astrocytic tumors, WHO grades III and IV. Only minor groups of pure oligodendrogliomas have been investigated. The aim of the investigation was to study the expression of the 3 NOS isoforms in this genetically divergent group of primary gliomas and to correlate the findings with tumor grade and expression pattern for the major group of gliomas--the astrocytomas. We examined the NOS expression in 35 oligodendrogliomas, WHO grade II, and 7 anaplastic oligodendrogliomas, WHO grade III, by immunohistochemical methods using formalin-fixed paraffin-embedded material. We observed only a minor expression of nNOS and sparse expression of eNOS in the tumor cells, but a vivid expression of eNOS in the vascular endothelial cells in both the tumor and the surrounding tissue. The rich expression of eNOS in oligodendroglioma vessels independent of tumor grade may suggest that blood flow and angiogenesis in these richly vascularized tumors are modified by NO. Interestingly, enhanced expression of inducible NOS was observed in the oligodendroglial tumor cells in 19 of 35 oligodendrogliomas (54%) and in 2 of 7 anaplastic oligodendrogliomas (29%). This is diverging for iNOS expression in astroglial tumors and the data could be indicative of iNOS exerting anti-tumor activity which may protract the progression from low-grade oligodendrogliomas to more anaplastic types. PMID- 11758778 TI - Slowly progressive dementia and multiple cerebral cortical infarctions following mitral valve replacement. AB - We describe the clinicopathological findings of a woman, 83 years of age at the time of death, who demonstrated dementia and numerous cerebral infarctions. She had a history of repeated mitral valve replacements 15 and 13 years prior to death and showed a dull responsive state 1 month after the second operation. Thereafter, dementia manifested and slowly progressed. Brain computed tomography revealed cortical atrophy and ventricular dilatation. Histological examination revealed a large number of minute foci of infarction in the cerebral cortex. Such lesions may have developed in association with the valve replacement and resulted in progressive dementia. PMID- 11758779 TI - Immunohistochemical localization of phosphoinositide 3-kinase in brains with multiple system atrophy. AB - Oligodendrocytes have been shown to display some morphological characteristics of apoptosis in MSA. The accumulated evidence shows that phosphoinositide 3-kinase (PI3K) is closely associated with the regulation of apoptosis. Thus, we examined immunohistochemically PI3K in the cerebellum and pons from autopsy samples with MSA. In control tissues, PI3K was immunostained in some neurons and a few oligodendrocytes. In MSA samples, the larger number of oligodendrocytes was observed in the pons and cerebellum. Furthermore, some neurons were strongly immunolabeled in MSA samples. The recent study has shown that PI3K phosphorylates PKB/Akt which phosphorylates BAD resulting in the cessation of apoptotic process. The present results suggest that PI3K is upregulated in oligodendrocytes and some neurons in MSA, possibly in response to the apoptotic signals to these cells. PMID- 11758780 TI - Rhabdoid glioblastoma. AB - Rhabdoid phenotypic change has been described in a number of different neoplasms from diverse organ sites. These tumors share common light and electron microscopic features, display a polyphenotypic immunohistochemical profile and often show cytogenetic abnormalities of chromosome 22. In the central nervous system (CNS), most rhabdoid tumors occur in the posterior fossa of very young children and are associated with a primitive neuroectodermal tumor (PNET) component and are designated atypical teratoid/rhabdoid tumors. Infrequently, other rhabdoid tumors of the CNS have been described, including rhabdoid meningiomas and malignant rhabdoid tumors of uncertain histogenesis. Several examples of conventional gliomas displaying significant areas with rhabdoid morphology were also presented in an abstract by Kepes and Moral [1991], although never published in final manuscript form. We now detail the case of an 18-year old male with an aggressive, supratentorial CNS rhabdoid tumor that was associated with an epithelioid glioblastoma and apparently arose from areas of low-grade glioma. The rhabdoid tumor component was present in the original tumor but became more predominant with each of 3 successive resections. No areas of PNET were identified. Electron microscopy and immunohistochemistry showed features classic for rhabdoid tumors and cytogenetic studies demonstrated multiple tumor clones with monosomy 22. This case documents progressive rhabdoid transformation of a glioma, expands the spectrum of CNS tumor types that can display a rhabdoid phenotype and highlights the diagnostic and therapeutic challenges with this type of tumor. PMID- 11758781 TI - Suprasellar monomorphous pilomyxoid neoplasm: an ultastructural analysis. AB - The authors report 3 patients, 2 children and 1 adult, each of whom presented with an unusual myxoid lesion reminiscent of pilocytic astrocytoma but with other features of myxopapillary ependymoma. The magnetic resonance imaging findings in all cases showed a diffusely contrast-enhancing suprasellar mass focally extending into the third ventricle. Involvement of adjacent structures was more extensive in both infants. By light microscopy, all were composed of a monotonous population of cells with delicate piloid-like processes, loosely arranged within a prominent myxoid background. Focally, the neoplastic cells converged upon small blood vessels in pseudorosette-like formations. These histomorphologic features are identical to those of the recently described astrocytoma with monomorphous pilomyxoid features. In addition, the individual tumor cells showed strong cytoplasmic immunoreactivity with antibodies to glial fibrillary acidic protein (GFAP) and vimentin, as well as nuclear and cytoplasmic staining with S-100. All stained positive for synaptophysin and negative for chromogranin. By electron microscopy, the tumor cells were bipolar with elongated processes and apical surfaces displaying microvilli, cytoplasmic blebs and rare cilia. Vesicles and coated pits were seen, as were occasional synaptoid complexes. The current study serves to expand our clincopathologic experience with this rare and enigmatic lesion, with particular attention given to the ultrastructural characteristics. PMID- 11758782 TI - Specificity and sensitivity of betaAPP in head injury. AB - INTRODUCTION: Beta-amyloid precursor protein (betaAPP) expression has been found in traumatic brain injury, hypoxia, ischemia and infection which affect axonal transport. Although betaAPP is a sensitive marker for detecting axonal damage, it has become non-specific for a particular type of injury. The aim of this study was to identify a difference in the pattern, distribution and intensity of betaAPP expression in head injury compared to hypoxic/ischemic insults. MATERIALS AND METHODS: Thirteen primary head injury and 12 primary hypoxic/ischemic cases were selected. The anterior and posterior parts of corpus callosum, internal capsule (basal ganglia), middle cerebellar peduncles (cerebellum) and pons were examined and stained immunohistochemically for betaAPP antibody. A computerized system of image analysis was used to examine the intensity (strength of staining) and density (area fraction) of betaAPP. RESULTS: Significant differences were observed in the overall intensity and density of betaAPP expression (p < 0.05) and in all 5 brain regions in cases of head injury compared to the hypoxic/ischemic group (p < 0.05). Positive staining for betaAPP was found in all regions in all cases of head injury, however, 4 out of 12 cases of hypoxia/ischemia were positive for betaAPP. One case expressed positivity in all 5 regions, 2 cases exhibited positivity in the pons alone, with only 1 case exhibiting immunoreactivity in the posterior corpus callosum and internal capsule. Differences in the pattern of betaAPP expression identified a predominantly granular pattern with a dirty background seen in hypoxia/ischemia, while fusiform swellings, beaded and thick filaments with clear background were observed in head injury. CONCLUSION: There are differences in the pattern, distribution and intensity of betaAPP in head injury compared to hypoxia/ischemia. These could be due to pathophysiological differences. The results may be helpful in differentiating head injury from hypoxia in medicolegal cases. PMID- 11758783 TI - Leptomeningeal signet-ring cell carcinomatosis presenting with ophthalmoplegia, areflexia and ataxia. AB - We report a very rare case of occult leptomeningeal carcinomatosis (LC) in whom repeated cytological examination did not show malignant cells in cerebrospinal fluid (CSF) and the primary focus was not discovered by extensive survey. The patient presented with ophthalmoplegia, ataxia and areflexia mimicking Miller Fisher syndrome (MFS) at the initial stage, and later, the clinical profile and laboratory findings including CSF examination simulated tuberculous meningitis. Postmortem autopsy disclosed metastatic signet-ring cell carcinoma infiltrating into cranial nerves and leptomeninges. We would like to emphasize that LC sometimes shows symptoms and signs similar to MFS or tuberculous meningitis. PMID- 11758784 TI - Neuropathology and neurodegeneration in HIV infection. PMID- 11758785 TI - Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice. AB - Embryonic induction of hair follicles is a fascinating model of localized morphogenesis from a simple homogeneous epithelial cell sheet. Accumulating evidence indicates that Sonic hedgehog (Shh) signaling plays a central role in hair follicle formation. We quantitated the expression levels of Shh and its receptor genes, Patched (Ptc) and Patched-2 (Ptch2), in two distinct experimental systems in which the development of hair follicles was suppressed. Shh, Ptc, and Ptch2 were induced about six- to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture. This induction was almost completely inhibited both in the developing skin tissue of ICR mice cultured with 30ng/ml epidermal growth factor and in embryos of Tabby mutant mice (a model of hypohidrotic ectodermal dysplasia) at 14.5-15.5 days postcoitus. Expression of Shh, Ptc and Ptch2 was induced in the Tabby embryos at 16.5 days postcoitus, indicating that Shh signaling may be involved in the formation not only of the well-studied guard hair but also of the awl hair. The potential of the two biological systems for studying molecular mechanisms in hair follicle formation, particularly at an early phase including Shh signaling, is discussed. PMID- 11758786 TI - Proliferative activity of CD8(+) T cells as an important clue to analyze T cell mediated inflammatory dermatoses. AB - To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. PMID- 11758787 TI - In situ expression of the costimulatory molecules CD80 and CD86 on langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis. AB - The functional expression of costimulatory molecules on antigen-presenting cells may be a key event in the pathogenesis of atopic dermatitis (AD). Recently, the expression of CD86 (B7-2/B70) has been demonstrated on CD1a+ epidermal dendritic cells (DC) in AD lesions by immunohistological and functional analysis. Therefore, we sought to further characterize the in situ expression of costimulatory molecules on these cells, considering the two subpopulations of (1) CD1a+++/CD11b- Langerhans cells (LC) containing Birbeck granules and (2) CD1a+/CD11b+++ inflammatory dendritic epidermal cells (IDEC), devoid of Birbeck granules, from AD and other inflammatory skin diseases. Flow cytometry, skin mixed lymphocyte reactions (SMLR) and immunohistological analysis were performed, and showed that IDEC and not LC are the relevant cells expressing the costimulatory molecules CD80 and CD86 in situ. This expression varied with the underlying diagnosis, with AD showing the highest expression of both CD80 and CD86 in situ. Furthermore, the expression of CD80, CD86 and CD36 were significantly correlated. With short-term culture, both CD80 and CD86 were further upregulated on LC and IDEC. Finally, anti-CD86 antibody reduced the stimulatory activity of epidermal DC. These results indicate that costimulatory molecules on LC and IDEC might play a role in the pathogenesis of AD. PMID- 11758788 TI - Anti-U1RNP antibodies in patients with localized scieroderma. AB - Antibodies to U1 ribonucleoproteins (RNP) have been detected in serum from patients with various autoimmune diseases. However, the presence of anti-U1RNP antibodies in patients with localized scleroderma has not been reported. In this study, we examined the frequency of anti-U1RNP antibodies using immunoprecipitation of U small nuclear RNAs and determined the antigen specificity by immunoblotting. Of 70 serum samples from patients with localized scleroderma, 2 (3%) immunoprecipitated U1 small nuclear RNA. Indirect immunofluorescence using HEp-2 cells as substrate showed coarse speckled nuclear fluorescence without nucleolar staining in both of the samples positive for anti U1RNP antibodies. In addition, the presence of anti-U1RNP antibodies in each serum sample was confirmed by immunodiffusion against HeLa cell extracts. Immunoblotting analysis showed anti-70 kDa antibodies in each serum sample. This reaction against 70 kDa protein in the patients with localized scleroderma was analogous to that in patients with systemic sclerosis or mixed connective tissue disease. Both patients with positive serum were diagnosed as having linear scleroderma, but neither had evidence of Raynaud's phenomenon or sclerodactyly. These results indicate that the presence of anti-U1RNP antibodies is one of the serological abnormalities in localized scleroderma, and that the mechanism of induction of anti-U1RNP antibodies in patients with localized scleroderma might be similar to that in patients with systemic sclerosis and mixed connective tissue disease. PMID- 11758789 TI - Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis. AB - Tuberous sclerosis complex (TSC) is a multisystemic disorder characterized by systemic hamartomas. Although the disease-determining genes TSC1 and TSC2 have been isolated, the molecular pathogenesis of the disease is not understood. We examined cell cycle abnormalities in skin specimens and cultured cells derived from specific lesions of TSC patients with confirmed TSC1 or TSC2 mutations. None of the specimens used in this study showed loss of heterozygosity (LOH). We detected more cells positive for PCNA and fewer cells positive for MPP2 in the epidermis of TSC patients than in the epidermis of control patients without TSC. Incorporation of 5-bromo-2-deoxyuridine (BrdU) was similar in fibroblasts derived from TSC lesions and in normal human fibroblasts. These results suggest that the cell cycle of TSC cells shows a prolonged S phase. Flow cytometric analysis confirmed S phase prolongation in TSC cells. Many apoptotic cells were detected by a nick end labeling assay in both skin tissue and cultured fibroblasts derived from specific TSC lesions. Examination of cyclin levels showed increased nuclear cyclin A and cytoplasmic cyclin B and decreased nuclear cdc2 levels. We conclude that suppression of either TSC1 or TSC2 may change cyclin levels, prolong S phase and induce apoptotic cell death. PMID- 11758790 TI - Water modulation of stratum corneum chymotryptic enzyme activity and desquamation. AB - Exposure to a dry environment leads to depletion of water from the peripheral stratum corneum layers in a process dependent on the relative humidity (RH) and the intrinsic properties of the tissue. We hypothesized that by modulating the water content of the stratum corneum in the surface layers, RH effects the rate of desquamation by modulating the activity of the desquamatory enzymes, and specifically stratum corneum chymotryptic enzyme (SCCE). Using a novel air interface in vitro desquamatory model, we demonstrated RH-dependent corneocyte release with desquamatory rates decreasing below 80% RH. Application of 10% glycerol or a glycerol-containing moisturizing lotion further increased desquamation, even in humid conditions, demonstrating that water was the rate limiting factor in the final stages of desquamation. Furthermore, even in humid conditions desquamation was sub-maximal. In situ stratum corneum SCCE activity showed a dependence on RH: activity was significantly higher at 100% than at 44% RH. Further increases in SCCE activity were induced by applying a 10% glycerol solution. Since SCCE, a water-requiring enzyme, must function in the water depleted outer stratum corneum, we sought to determine whether this enzyme has a tolerance to lowered water activity. Using concentrated sucrose solutions to lower water activity, we analysed the activity of recombinant SCCE and compared it to that of trypsin and chymotrypsin. SCCE activity demonstrated a tolerance to water restriction, and this may be an adaptation to maintain enzyme activity even within the water-depleted stratum corneum intercellular space. Overall these findings support the concept that in the upper stratum corneum, RH modulates desquamation by its effect upon SCCE activity, and possibly other desquamatory hydrolases. In addition, SCCE may be adapted to function in the water-restricted stratum corneum intercellular space. PMID- 11758791 TI - Drastic decrease in environmental humidity decreases water-holding capacity and free amino acid content of the stratum corneum. PMID- 11758792 TI - Dogs and the heart. PMID- 11758793 TI - Neurogenic female sexual dysfunction: a review. AB - The effect of various spinal lesions on female sexual response has recently been investigated in detail. Studies of women with neurologic disabilities and studies of animal models have provided substantial information regarding the spinal control of sexual responses. In this report, the authors explore findings regarding the neurologic pathways underlying the spinal control of sexual arousal and orgasm. Information available about the effects of multiple sclerosis and various cerebral disorders on female sexual function will also be reviewed, with special attention to areas where further research is needed. Lastly, the current status and techniques available to improve the sexual functioning of women with neurologic disabilities affecting the central nervous system will be reviewed. PMID- 11758794 TI - Neurogenic erectile dysfunction. AB - Penile erection is a neurovascular event modulated by psyche and hormones. Erectile dysfunction (ED) has been classified as psychogenic, arteriogenic, neurogenic, endocrinologic, and cavernosal, based on the organs that are involved in penile erection. Among these types, neurogenic ED may be the most common, probably because a deficiency of neurotransmitters is the final common pathway in many diseases and conditions. This review discusses the physiology, pathophysiology, diagnosis, and treatment of erectile function and dysfunction, as well as strategies for future research. PMID- 11758795 TI - Influences of female reproductive hormones on sympathetic control of the circulation in humans. AB - The significant increase in cardiovascular disease risk with the loss of estrogen and progesterone at menopause has lead to increasing interest in the cardiovascular influences of female reproductive hormones. In addition to direct influences of estrogen to promote endothelium-dependent vasodilation, recent evidence demonstrates important influences of both estrogen and progesterone on the neural control of the peripheral circulation. These influences have been studied in two general contexts. First, the effects of these hormones on the sympathetic control of the cutaneous circulation have received substantial attention. The control of neurogenic vasodilation in the skin in response to hyperthermia is shifted to higher and lower internal temperatures by progesterone and estrogen, respectively. Reflex vasoconstrictor control of skin blood flow is shifted to higher internal temperatures when the hormones are elevated. Second, reproductive hormones have recently been shown to significantly alter sympathetic neural control of the skeletal muscle circulation. Sympathetic neural control of the skeletal muscle circulation (measured directly as muscle sympathetic nerve activity [MSNA]) is altered by hormone status such that resting MSNA is decreased by estrogen, as is the MSNA response to exercise. Furthermore, the baroreflex control of MSNA is significantly modified by estrogen and progesterone. Therefore, female reproductive hormones have widespread influences on the sympathetic control of the circulation in humans. The individual influences of estrogen and progesterone often antagonize one another, and when both hormone concentrations are increased, the net effect probably depends on their relative concentrations and bioactivity. The mechanisms responsible for these influences and their health-related implications deserve further attention. PMID- 11758796 TI - Aphrodisiacs past and present: a historical review. AB - The drug Viagra (sildenafil) has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Aphrodisiacs can be classified by their mode of action into 3 types: those that increase (1) libido, (2) potency, or (3) sexual pleasure. Various substances of animal and plant origin have been used in folk medicines of different cultures; some have been identified pharmacologically, allowing for understanding of their mechanisms of action. For increasing libido, ambrein, a major constituent of Ambra grisea, is used in Arab countries. This tricyclic triterpene alcohol increases the concentration of several anterior pituitary hormones and serum testosterone. Bufo toad skin and glands contain bufotenine (and other bufadienolides), a putative hallucinogenic congener of serotonin. It is the active ingredient in West Indian "love stone" and the Chinese medication chan su. The aphrodisiac properties are likely of central origin, as are the other effects of the drug. For increasing potency, Panax ginseng used in traditional Chinese medicine, works as an antioxidant by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa; ginsenosides also enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cyclic guanosine monophosphate, hence the aphrodisiac properties. For increasing sexual pleasure, cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which have been used for millennia as a sexual stimulant. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of beta-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The ingestion of live beetles (Palembus dermestoides) in Southeast Asia and triatomids in Mexico may have a basis similar to cantharidin. It is of paramount importance for the physician to be aware of the options available to help his or her patients, and to advise them in using the correct drugs while avoiding "miracle" remedies that could be potentially harmful. PMID- 11758797 TI - Isolated urinary retention in young women, or Fowler's syndrome. AB - A group of women with otherwise unexplained urinary retention occurring as an isolated phenomenon have been shown to have abnormal urethral sphincters, as assessed by electromyography, transvaginal ultrasonographic volume and pressure profile. A questionnaire survey of a number of women diagnosed with the disorder showed that there was a common natural history, and from the results it was possible to build up a profile of the "typical" patient. She is likely to be between 20 and 35 years old and also to have polycystic ovaries. Before the onset of retention she is likely to have had a relatively mild voiding dysfunction, such as infrequent voiding or an intermittent stream. Commonly her first retention episode will follow a triggering event such as an operation or childbirth. The retention is unlikely to resolve but is not associated with the development of other disorders. Neuromodulation of the sacral nerves is the only intervention that has been demonstrated to restore voiding. PMID- 11758798 TI - Presence of a pet dog and human cardiovascular responses to mild mental stress. AB - The mechanisms underlying the possible cardiovascular benefits of pet ownership have not been established. Using a randomized design, the effect of a friendly dog on cardiovascular and autonomic responses to acute, mild mental stress was investigated. Seventy-two subjects (aged 40 +/- 14 y; mean +/- SD) participated. Rest was alternated with mental stress during four 10-minute periods. An unknown dog was randomly selected to be present during the first or the second half of the study. Blood pressure (BP) and heart rate (HR) were monitored continuously and cardiac autonomic function assessed using spectral analysis of heart period. Heart period variability data were expressed as the ratio of 0.1 Hz to respiratory or high frequency variation (LF/HF). Whereas mental stress significantly increased BP and HR in the absence of the dog (from 125/71 +/- 3/2 to 133/75 +/- 3/2 mm Hg; p <0.001), the presence of the dog had no effect on these variables. Heart period LF/HF ratio was lowest in dog owners in the presence of the dog (dog present 2.8 +/- 0.3 versus dog absent 3.4 +/- 0.4; p <0.001) and in non-dog owners in the absence of the dog (dog present 3.4 +/- 0.4 versus dog absent 2.8 +/- 0.3; p <0.001). In conclusion, a friendly but unfamiliar dog does not influence BP or HR either at rest or during mild mental stress. Cardiac autonomic profile was most favorable in the presence of the dog for dog owners and in the absence of the dog for non-owners. PMID- 11758800 TI - Myosin light chain kinase as a multifunctional regulatory protein of smooth muscle contraction. AB - Myosin light chain kinase (MLCK) is a regulatory protein for smooth muscle contraction, which acts by phosphorylating 20-kDa myosin light chain (MLC20) to activate the myosin ATPase activity. Although this mode of action is well established, there are numerous reports of smooth muscle contraction that is not associated with MLC20 phosphorylation. The kinase activity for the phosphorylation is localized at the central part of MLCK, which is also furnished with actin-binding activity at its N terminal and myosin-binding activity at its C terminal. This article overviews as to how such multifunctional properties of MLCK modify the actin-myosin interaction and presents our observations that the phosphorylation is not obligatory in induction of smooth muscle contraction. PMID- 11758799 TI - Autonomic and cardiovascular function in HIV spectrum disease: early indications of cardiac pathophysiology. AB - Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reported previously but its incidence in early stage HIV infection and its relation to cardiovascular function have not been fully examined. The present study evaluated cardiovascular and autonomic function in 55 HIV-seronegative, and 52 HIV-asymptomatic and 31 HIV-symptomatic seropositive men. Measures of hemodynamic and autonomic function were obtained at rest and during a standardized battery of autonomic tests. Results were compared across groups while controlling for age, body mass, and physical activity. Analyses indicated that measures of autonomic function did not differ among groups. However, at rest, both HIV seropositive groups exhibited diminished stroke volume and elevated diastolic blood pressure, albeit within normotensive levels. In addition, the ability to sustain a blood pressure response during prolonged challenge and the relationship between stroke volume and baroreceptor/vagal responsiveness were disrupted in the HIV-symptomatic group. Therefore, in the pre AIDS stages of infection, autonomic functioning appeared intact; yet alterations in baroreceptor/vagal function associated with depressed myocardial function may be an early warning signal reflecting cardiovascular pathological processes potentially exacerbated by HIV spectrum disease. PMID- 11758801 TI - Translocation of proteins into mitochondria. AB - The translocase of the outer mitochondrial membrane (TOM) is composed of receptors, a channel protein, and its modulators that function together to import proteins into mitochondria. Although the import pathway of proteins directed to the mitochondrial matrix has been well characterized, recent studies into the import pathway taken by proteins into the other submitochondrial compartments have broadened our understanding into the way the TOM machinery recognizes, interacts, and translocates proteins. PMID- 11758802 TI - Spectroscopic contributions to the understanding of hemoglobin function: implications for structural biology. AB - Structural biology is based on the assumption that structural determinations will explain macromolecular function. To examine the basis of these proposals, the structure/function connections in hemoglobin have been examined. Presently the Monod, Wyman, Changeux (MWC) model of hemoglobin function has great validity. In this model, ligand-binding affinities are linked to quaternary structure, and it has been shown that the model describes the function accurately to a high first approximation. To see how this understanding developed, we review two sets of experimental studies in 1970-71 that supported the applicability of MWC to hemoglobin oxygen binding. One set of data from NMR and ligand binding kinetics supported the quaternary-linked nature of binding required by the MWC model. The other approach, by Perutz, proposed a structural basis for MWC, by suggesting that in one quaternary structure the binding of oxygen broke a salt bridge that caused a lowered quaternary-linked affinity. However, experiments since that time, mostly by X-ray crystallography of deoxygenated hemoglobin, have failed to show salt bridges breaking upon ligation, whereas affinities have remained low. This pattern of results shows that the small energies responsible for ligand binding affinities and reaction rates have not been identified by discrete structural features. Rather, thermodynamic and kinetic data from a variety of spectroscopic studies have played the central role in establishing the MWC model for hemoglobin. PMID- 11758803 TI - Role of LIM domains in mediating signaling protein interactions. AB - LIM domains are double zinc-finger motifs that mediate protein interactions between transcription factors, cytoskeletal and signaling proteins. This review outlines the protein interactions mediated by LIM domains with signaling proteins including tyrosine and serine/threonine kinases and phosphatases. PMID- 11758804 TI - Signaling by the respiratory burst in macrophages. AB - During phagocytosis or stimulation with a wide variety of agents, macrophages and other phagocytic cells produce reactive oxygen species (ROS) through activation of a multicomponent NADPH oxidase. ROS production through related NADPH oxidases has recently been demonstrated in several other cell types. Furthermore, the physiological generation of ROS production has now been clearly implicated in activating signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis. This brief review suggests that: 1) hydrogen peroxide and superoxide, but not the hydroxyl radical, function as second messengers; 2) antioxidant enzymes function in the "turn-off" phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the primary physiological role of the respiratory burst in macrophages may be in redox signaling rather than microbicidal activity. PMID- 11758805 TI - Conformation changes in brain calcineurin in diabetic rats with or without treatment with vanadyl sulfate. AB - Recent studies have shown that vanadium salts are able to reduce blood glucose in diabetics and overcome, to some degree, insulin resistance. This paradigm has been followed to monitor the effects of diabetes and vanadyl treatment on brain calcineurin (CN), an important protein phosphatase. Male rats were rendered diabetic by a single injection of streptozotocin (STZ), resulting in an elevation of blood glucose from 108 +/- 13 to >400 mg/dl. Diabetic animals were given vanadyl sulfate trihydrate (0.5 mg/dl.) in their drinking water for 3 weeks, which led to a fall in blood glucose to 156 +/- 53 mg/ml. Brain CN activity (units/mg brain protein) in diabetic rats was 77% that of control animals, whereas vanadyl-treated diabetic animals were characterized by CN activities like that of controls. CN was purified from brains of control animals, STZ-induced diabetic animals, and STZ-induced diabetic animals receiving vanadyl, then spin labeled with 3-maleimide-proxyl and studied via electron spin resonance spectroscopy. The rotational correlation time of CN from control animals and vanadyl-treated diabetic animals was 6.4 x 10(-11) s(-1), whereas that from STZ induced-diabetic animals was 8 x 10(-11) s(-1). Thus, STZ-induced diabetes in rats results in an increase in the rotational correlation time of brain CN relative to control animals, yet vanadyl treatment of STZ-induced diabetic animals reduced the rotational correlation time to that of control. These data suggest that diabetes can lead to apparent conformational changes in brain CN; also, CN conformation in diabetic rats was restored by vanadyl treatment. PMID- 11758806 TI - Free radical-induced protein degradation of erythrocyte membrane is influenced by the localization of radical generation. AB - We have investigated the role of the localization of free radical generation in erythrocyte membrane proteins degradation. The extracellular radical producer 2,2'-azobis(2-amidinopropane) hydrochloride induced a greater loss of band-3 protein in comparison with spectrin whereas the intracellular radical initiator cysteine induced the reverse effect. However, a large extent of main-chain fragmentation was observed for both proteins under the action of cysteine-derived radicals. The results show that the relative localization of the radical generation has an important influence on the degradation of specific proteins of the erythrocyte membrane. PMID- 11758807 TI - IL-1beta increases uPA and uPA receptor expression in human gingival fibroblasts. AB - The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) in various cell types has been proposed as an important feature of many cellular processes requiring extracellular proteolysis, cell adhesion, motility, and invasion. uPAR attaches to the cell surface with a glycosylphophatidylinositol (GPI) anchor, and serves to localize and accelerate the proteolysis cascade. In this study, we examined both uPA and uPAR levels in human gingival fibroblasts treated with an inflammatory cytokine, interleukin-1beta (IL-1beta). PA activity in the cell lysate was increased by treatment with IL-1beta. Further, PA activity released by phosphatidylinositol-specific phospholipase C, which detaches the GPI anchor, was also increased by IL-1beta. The activity was inhibited by amiloride, a specific inhibitor of uPA. In addition, IL-1beta increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts. These findings suggest that the enhancement of uPA and uPAR levels by IL-1beta may play an important role in the progression of periodontal diseases through pericellular proteolysis, and subsequent cellular behavior. PMID- 11758808 TI - Immunoexpression of interleukin-1beta in pancreatic islets of NOD mice during cyclophosphamide-accelerated diabetes: co-localization in macrophages and endocrine cells and its attenuation with oral nicotinamide. AB - During insulin-dependent diabetes mellitus, islet invading immune cells destroy beta cells over a prolonged asymptomatic pre-diabetic period. Cytokines synthesised and secreted by specific immune cells within the islet infiltrate may be crucial effectors of beta cell destruction or protection during the disease. Interleukin-1beta may be a key cytokine which may act in concert with other cytokines in initiating and/or promoting beta cell destruction. We have examined this hypothesis in NOD mice by assessing the intra-islet expression and co localization of interleukin-1beta at different time-points following cyclophosphamide administration. We have also tested the effects of long-term oral nicotinamide given to NOD mice in suppressing intra-islet expression of the cytokine in this accelerated model. Cyclophosphamide was administered to day 95 female NOD mice. Pancreatic tissues were examined by dual-label confocal immunofluorescence microscopy for the expression and co-localization of interleukin-1beta at days 0, 4, 7, 11 and at onset of diabetes (day 14). Diabetes developed in 7/11 mice 14 days after administration of cyclophosphamide while nicotinamide completely prevented the disease. At day 0, interleukin-1beta immunolabelling was observed in selective intra-islet macrophages, several somatostatin cells and in a few beta cells. However, at day 4, it was seen mostly in somatostatin and some beta cells. At day 7, an increasing number of interleukin-1beta cells were observed within the islets and co-localized to several somatostatin cells, beta cells and macrophages. The mean number of intra islet interleukin-1beta cells reached a peak at day 11 and was significantly higher than at day 7 (p = 0.05) and at day 14 (onset of diabetes; p = 0.03). At day 11, interleukin-1beta immunolabelling was also present in selective macrophages which co-expressed inducible nitric oxide synthase. At onset of diabetes, some macrophages, residual beta cells and somatostatin cells showed immunolabelling for the cytokine. Exposure of NOD mice to oral nicotinamide was associated with a considerably reduced expression of interleukin-1beta cells within the islet at day 11 (p = 0.002). We conclude that cylophosphamide treatment enhances the expression of interleukin-1beta in selective macrophages, somatostatin and beta cells during the course of the disease. Its expression reaches a maximum immediately prior to onset of diabetes. Interleukin-1beta present in intra-islet macrophages, somatostatin and beta cells may influence its expression by autocrine and paracrine means. Interleukin-1beta expression within islet macrophages may also up-regulate inducible nitric oxide synthase within the same macrophage or adjacent macrophage populations. These intra-islet molecular events may corroborate with other local cytotoxic processes leading to beta cell destruction. Oral nicotinamide may attenuate intra-islet expression of interleukin-1beta and thus inducible nitric oxide synthase during prevention of Type 1 diabetes in this animal model. The expression of interleukin-1beta in specific islet endocrine cell-types shown in this study requires further investigation. PMID- 11758809 TI - Distribution of microsomal epoxide hydrolase in humans: an immunohistochemical study in normal tissues, and benign and malignant tumours. AB - Microsomal epoxide hydrolase is a biotransformation enzyme which is involved in the hydrolysis of various epoxides and epoxide intermediates. In the present study, its distribution was investigated in both normal human tissues and human tumours of different histogenetic origin using immunohistochemical techniques. In normal tissue, epithelial cells were more often and more intensely immunostained than mesenchymal cells. The main epithelial cell types expressing microsomal epoxide hydrolase were hepatocytes, acinus cells of the pancreas, and cells of salivary and adrenal glands. Immunostained cells of mesenchymal origin included monocytes, fibrocytes, fibroblasts, vessel endothelium, muscle cells, and cells of the reproductive system. Three patterns of expression were observed in tumour tissues: (1) moderate or strong in hepatocellular carcinomas, tumours of the adrenal gland, and theca-fibromas of the ovary; (2) inhomogeneous staining pattern of variable intensity in breast cancer, lung cancer, colorectal carcinomas, carcinoid tumours, and some tumours of mesenchymal origin; and (3) no expression in malignant melanomas, malignant lymphomas, and renal carcinomas. These data indicate that microsomal epoxide hydrolase expression is not restricted to tissue of any particular histogenetic origin. Nonetheless, immunohistochemical identification of microsomal epoxide hydrolase may be helpful in some well-defined histological settings, for example, confirmation of hepatocellular carcinoma. PMID- 11758810 TI - H+ and HCO3- transporters in human salivary ducts. An immunohistochemical study. AB - The presence and cellular distribution of key H+ and HCO3- transport proteins was studied in human salivary ducts. Immunofluorescence and immunoperoxidase light microscopy was applied, using specific antibodies against the NHE1 and NHE3 isoforms of the Na+/H+ exchanger, against the 31 and 70 kDa subunits of the vacuolar H+-ATPase and against the electrogenic Na+-HCO3- cotransporter. The results show basolateral NHE1 and apical NHE3 in human submandibular, parotid and sublingual duct cells. Vacuolar H+-ATPase was found predominantly in the apical membrane of parotid, submandibular and sublingual duct cells, although it was absent in certain parotid striated duct cells. The Na+-HCO3- cotransporter was predominantly expressed in the apical membrane of parotid and sublingual striated ducts, and intracellularly distributed in the distal parts of the gland tree and in submandibular ducts. The results indicate that HCO3- transport properties of salivary ducts may vary not only between gland and species, but even in different duct segments of the same gland as well. PMID- 11758811 TI - Localization of glucose-6-phosphate dehydrogenase activity on ribosomes of granular endoplasmic reticulum, in peroxisomes and peripheral cytoplasm of rat liver parenchymal cells. AB - Glucose-6-phosphate dehydrogenase activity has been localized ultrastructurally in fixed tissues. Activity was found in particular in association with ribosomes of granular endoplasmatic reticulum. Biochemical studies indicated that glucose-6 phosphate dehydrogenase activity is also present in the cytoplasm and in peroxisomes. Fixation may be held responsible for selective inactivation of part of glucose-6-phosphate dehydrogenase activity. In the present study, we applied the ferricyanide method for the demonstration of glucose-6-phosphate dehydrogenase activity in unfixed cryostat sections of rat liver in combination with the semipermeable membrane technique and in isolated rat liver parenchymal cells. Isolated liver parenchymal cells were permeabilized with 0.025% glutaraldehyde after NADP+ protection of the active site of glucose-6-phosphate dehydrogenase. This treatment resulted in only slight inactivation of glucose-6 phosphate dehydrogenase activity. The composition of the incubation medium was optimized on the basis of rapid light microscopical analysis of the formation of reddish-brown final reaction product in sections. With the optimized method, electron dense reaction product was observed in cryostat sections on granular endoplasmic reticulum, in mitochondria and at the cell border. However, the ultrastructural morphology was rather poor. In contrast, the morphology of incubated isolated cells was preserved much better. Electron dense precipitate was found on ribosomes of the granular endoplasmic reticulum, in peroxisomes and the cytoplasm, particularly at the periphery of cells. In conclusion, our ultrastructural study clearly demonstrates that it is essential to use mildly fixed cells to allow detection of glucose-6-phosphate dehydrogenase activity in all cellular compartments where activity is present. PMID- 11758812 TI - Sialoglycoconjugate expression in acinar cells of rat developing submandibular gland. AB - Direct and indirect staining procedures were developed to characterize sialoglycoconjugates in developing rat submandibular gland. Lectin histochemistry, with and without prior sialidase digestion, combined with differential oxidation and deacetylation procedures was performed in situ. This allowed the expression of sialic acids to be followed during acinar cell development. It was found that terminal periodate-labile sialic acids linked to beta-galactose occurred early. In contrast, the terminal disaccharide sialic acid N-acetylgalactosamine was only detectable at the adult stage and so was considered to be a good marker of the full maturity of this gland. The developing acinar cells were mainly characterized by C4-acetylated sialic acids belonging to short side-chains. Dimorphic expression of sialoglycoconjugate components was evident by postnatal day 44. PMID- 11758813 TI - Sialic acid derivatives and their distribution in rat sublingual gland acini during pre- and post-natal development. AB - Sialoglycoconjugates in rat sublingual gland acinar cells, at different stages of pre- and post-natal development, were investigated in situ with specific lectins and by the selective removal of terminal sialic acids. Cleavage of acetyl substituents sited in the pyranose ring and/or polyhydroxyl side chain was used as an additional means of characterising the glycoconjugates. The first expression of terminal sialic acid linked to beta-galactose was found at gestational day 17 and progressive different derivatives were observed. The terminal disaccharide sialic acid-N-acetylgalactosamine was constantly visualized in the sublingual gland from gestational day 18. In both terminal disaccharides, sialic acids were characterized by variable degrees of acetylation and were found to be highly packaged and responsible for the hydration coat. The complex data obtained indicated that the sublingual gland is characterized by a marked fluctuation of complex sialoglycoconjugates that differ from those in the submandibular gland of the same species. PMID- 11758814 TI - Nerve cells associated with the endocrine pancreas in young mice: an ultrastructural analysis of the neuroinsular complex type I. AB - The neuroinsular complex type 1 is composed of pancreatic endocrine islet cells and nerve cell bodies intrinsic to the islet. The details of the relation between nerve cells and between endocrine cells and nerve cells in the complex are unknown. Pancreata from newborn and 18-day-old mice were analysed by electron microscopy to establish the ultrastructural morphology of the neuroinsular complex. Immunohistochemical staining for protein gene-product 9.5 was also performed. The study showed that nerve cell bodies were closely associated to each other in the periphery of the islets with no connective tissue separating the cells. The nerve cells were closely associated to both beta-cells and alpha cells. Direct intercellular contacts were observed between nerve cells and endocrine cells and between Schwann cells and endocrine cells. Varicose nerve endings were frequently observed in the neuroinsular complex. In the peripheral parts the varicosities were mostly being associated to the nerve cell bodies. The varicosities contained small clear or small clear and larger dense cored vesicles, suggesting cholinergic and peptidergic contents. The varicosities made specialized synaptic connections with adjacently located nerve cells. The study shows that the neuronal part of the neuroinsular complex is closely associated to the endocrine islet cells and that it is richly innervated, indicating an important regulatory function of the nerve cell component in the neuroinsular complex. PMID- 11758815 TI - Factors associated with frequent and infrequent HIV testing. AB - Drug user treatment clients with 5 or more HIV tests (frequent testees N=43) and 0-2 HIV tests (infrequent testees-N = 56) were compared on demographic characteristics, risk behaviors, perceived risk of HIV infection to self, involvement with family members, and psychological functioning. Extreme groups of HIV testees did not differ on any variables other than an index of perceived vulnerability to HIV infection (e.g., " You think that you really could get AIDS"). That measure of felt vulnerability was not correlated significantly with needle or sexual risk behaviors, family involvement, psychological functioning or other measures of perceived risk. It was reasoned that, in a community in which both dangers and protective behaviors are widely understood, frequent testees experience a generalized and heightened concern unrelated to specific behaviors or characteristics. PMID- 11758816 TI - An exploratory multivariate approach to drug consumption patterns in young people based on primary socialization theory. AB - Drug consumption patterns and their psychosocial conditioning factors are explored on the basis of Primary Socialization Theory (PST), through the application of a questionnaire to a representative sample (N= 650) of the young population (age 15 to 29 years) in the Madrid Region. Cluster analysis identifies five consumption groups. Discriminant analysis, including indicators about subject's integration in primary socialization environments, beliefs about the effects of drugs, indicators of psychosocial wellbeing, and variables related to leisure time, allows 67.45% of correct consumption group prediction. Complex associations between drug use, socialization environments and psychosocial wellbeing are found, calling into question approaches establishing cumulative or unidimensional relationships between posited "risk factors" and drug consumption. PMID- 11758817 TI - Substance use, need, and demand for substance user treatment services in patients treated for sexually transmitted diseases in michigan. AB - The association between substance use and communicable diseases, and the need for substance user treatment services for patients treated for communicable diseases, is well documented. This study builds upon this knowledge in that it quantifies the need and demand for substance user treatment services in a large population of patients treated for communicable diseases, specifically, sexually transmitted diseases (STDs), an area in which there is insufficient research published in the literature, but which is essential for policy development. More than 1700 patients treated for STDs in publicly funded clinics in Michigan between 1994 1995 were interviewed about their substance use, consequences of use and demand for substance user treatment services. Results indicated that the rates of substance use and demand for substance user treatment services were significantly higher among persons encountered in the STD clinics compared to the Michigan general adult population; however, a large proportion of STD patients determined to need substance user treatment services according to DSM-III-R criteria for "substance dependence" and "abuse" did not report ever receiving it. These results are followed by a discussion of possible policy implications for planning for substance user treatment services for patients treated for STDs in publicly funded clinics and suggestions for further research. PMID- 11758818 TI - Drug offenders in Taiwan and the United States: a cross-cultural analysis. AB - Using data collected from nationwide surveys of drug-using offenders in the United States and Taiwan, this article compares offender differences with respect to socio-demographic characteristics, childhood experiences, drug use and treatment patterns, and criminal histories. The results suggest that the experiences of U.S. drug-using offenders are more complex, with multiple routes and consequences of drug use, while the social constructionist view is more appropriate to explain the experience of Taiwanese drug-using offenders. Overall, U.S. drug-using offenders reported earlier drug and criminal involvement, experienced more prior arrests, and committed more non-drug-related crimes. Family problems were more prevalent among U.S. drug-using offenders than Taiwanese drug-using offenders. Drug-using offenders in the U.S. also reported using a variety of different drugs and participating in multiple treatment programs. The major agents supplying illicit drugs were known dealers, and friends or acquaintances of U.S. and Taiwanese drug-using offenders, respectively. The article concludes that to effectively eliminate the problem of drug misuse, the Taiwanese government should focus on treatment instead of imprisonment, while the U.S. should target troubled teens and families. PMID- 11758819 TI - Is the U.S. experiencing an incipient epidemic of hallucinogen use? AB - NHSDA and MTF survey data indicate "epidemic"-like growth in hallucinogen use from 1992-1996 and associated increases in cocaine, crack, heroin and amphetamine use. These trends might have resulted from a proliferation of raves and dance clubs in the U.S. as occurred in Europe and elsewhere, although in contrast to evidence regarding European experiences the American epidemic involves primarily teens as opposed to persons in their twenties and involves primarily use of LSD as opposed to MDMA. This analysis highlights the need for further research into the context, significance, and consequences of these recently popular American drug use practices. PMID- 11758820 TI - Reliability of drug users' self-reported HIV risk behaviors using a brief, 11 item scale. AB - This study evaluated the reliability of self-reported HIV risk behaviors in 84 substance misusers. The 11-item HIV Risk Behavior Scale was, used to evaluate lifetime, past month, and past week risk behaviors. Cronbach's alpha ranged from .75 to .80 for the three versions. Test-retest reliability for the lifetime version was excellent, with correlations of .90. In addition, 44 clients completed the weekly version once a week for four weeks, as well as the monthly version at the end of the same month. Reliability of responses collected weekly and monthly was good (r=.67, p < .001). Principal component analysis of the items confirmed that the scale measures two distinct HIV risk factors: one related to injecting behaviors and the other to sexual behaviors. These data suggest that the HRBS has satisfactory psychometric properties for measuring lifetime as well as recent HIV risk behaviors in substance misusers. Due to its brevity, this instrument may be a useful clinical and research tool. PMID- 11758821 TI - Comment on "nonresponse and selection bias in treatment follow-up studies". PMID- 11758822 TI - Downregulation of integrin-linked kinase mRNA expression by nitric oxide in rat glomerular mesangial cells. AB - Inflammatory glomerular diseases are accompanied by changes in the expression patterns of growth factors, mediators and matrix-associated proteins in mesangial cells and by the production of nitric oxide via the cytokine-inducible form of the nitric oxide synthase. Nitric oxide has been shown to act potently on gene transcription. To identify genes that are differentially expressed by endogenously produced nitric oxide, we forced rat mesangial cells to produce high amounts of nitric oxide by exposure to inflammatory cytokines and compared the mRNA expression patterns of cytokine-stimulated mesangial cells with cells that were additionally treated with the nitric oxide synthase inhibitor L-NMMA to block endogenous NO synthesis. We used a modification of a low stringency RT-PCR approach designated as RNA arbitrarily-primed polymerase chain reaction (RAP PCR). In this way, we identified among others the integrin-linked kinase (ILK) as an NO-regulated gene. The NO-mediated changes in the mRNA and protein expression patterns of ILK were compared to that of "secreted protein acidic and rich in cystein" (SPARC), a gene that was identified as NO-regulated in the same set of experiments (Walpen et al., J. Am. Soc. Nephrol., 11, 468-476). ILK and SPARC mRNA levels by were downregulated by cytokines via endogenously produced nitric oxide in a comparable manner as verified by Northern blot analysis. In contrast, cytokine- induced NO production or administration of exogenous NO-donors strongly reduced SPARC protein levels without altering ILK protein content in mesangial cells over a period up to 72 hours. Blocking de novo protein synthesis showed a short halflife of SPARC (< 2 hours) whereas ILK-protein was stable over a period of 7 hours, indicating that NO-mediated reduction of ILK mRNA levels does not influence protein content of ILK in mesangial cells under the time limitations given under cell culture conditions. However, a role for cytokines/NO in ILK-long term regulation in chronic inflammatory diseases that may influence phenotypic responses such as apoptosis or cell proliferation remains to be elucidated. PMID- 11758823 TI - Molecular steps of death receptor and mitochondrial pathways of apoptosis. AB - In almost all multicellular organisms, cell suicide or apoptosis appears to play an important role in the maintenance of cellular homeostasis. Apoptosis is tightly regulated by a set of genes that either promote apoptosis or promote cell survival. Although a number of stimuli appear to trigger the process of apoptosis, there are two major signaling pathways of apoptosis; the death receptor pathway and the death receptor-independent or mitochondrial pathway. There is evidence to suggest that, under certain conditions and in some cell types; these two pathways may cross talk. During the past 5 years, rapid progress has been made in understanding the molecular basis of apoptosis. In this brief review, I will summarize the various molecular steps of apoptosis. PMID- 11758824 TI - Effects of nimesulide and its metabolites or manufacturing intermediates on the viability and growth of the human hepatoma HepG2 cell line. AB - Hepatitis and fulminant hepatic failure have, infrequently, been associated with nimesulide. To establish if nimesulide or its analogues have direct cytotoxic activity on liver cells, experiments were undertaken to investigate the effects of nimesulide and its principal metabolites and production intermediates on the viability and growth of the human hepatoma cell line, HepG2, in vitro. The parent drug, metabolites or production intermediates as well as formulations of nimesulide were incubated for 6-48 hr with HepG2 cells and the extent of toxicity determined using the mitochondrial selective redox dye 3-4,5-dimethylthazol-2-yl) 2,4-diphenyl tetrazolium bromide (MTT). The results showed that there was no appreciable cytotoxic activity exhibited by nimesulide and its principle metabolites or production intermediates on HepG2 cells. PMID- 11758825 TI - Differential effects of non-genotoxic carcinogens and proliferating agents on cell growth, survival and apoptosis in hepatic cells in vitro. AB - Many nongenotoxic carcinogen's (ngc) produce hyperplastic lesions from which neoplastic foci may arise. Modulation of the rate of apoptosis by some ngc's within these lesions may be critical to their mechanism of tumour promotion but some may be cytotoxic. To establish if these compounds are apoptotic or necrotic in vitro, three ngc's (12-0-tetradecanoyl phorbol-13-acetate (TPA); nickel, and di(2-ethylhexyl-phthalate (DEHP), two noncarcinogenic hepatoproliferating agents (1,4-dichlorobenzene (DCB; HGF) and an in vitro genotoxic reference compound (7 hydroxy-2-acetylaminofluorene (70H2AAF) were used to induce mitogenic or growth responses in two liver cell-lines HepG2 and JTC-15. MTT and 3H-thymidine incorporation assays were used to measure cell growth and DNA replicative activity respectively. Rates of apoptosis were assayed using FITC-annexin V with propidium iodide staining and flow cytometry. Responses in HepG2 cells were HGF (proliferation at > or = 3 ng/ml), TPA (cell growth at > or = 8 ng/ml), DEHP (proliferation at > or = 0.05 microg/ml). NiCl2 and 70H-2AAF were cytotoxic above 0.001 microg/ml and 100 ng/ml respectively. An equivocal result was obtained for DCB. Responses in JTC-15 cells were HGF (proliferation, 3 ng/ml), TPA (DNA replication, 10 ng/ml), and DEHP (cell mass, 2.5 microl/ml). NiCl2 and 70H-2AAF were cytotoxic above 0.01 microg/ml and 110 mg/ml respectively. Equivocal results were obtained for DCB. In flow cytometry assays apoptotic and necrotic populations were not clearly separable. Approximate rates of apoptosis in HepG2 were: control 8.7%; DEHP, 10.19%. NiCl2, 12.67%; 70H2AAF, 16.56%; TPA, 19.72%; HGF, 23.73%; DCB, 24.59%; positive apoptotic control (taxol) 26.94%. These data show apoptosis was increased in chemically activated populations of HepG2. The ngc, DEHP, unexpectedtly produced proliferation in HepG2 and almost totally suppressed apoptosis in vitro in HepG2 relative to the non-carcinogenic hepatoproliferators. The rate of apoptosis induced by the ngc TPA was not considered to be sufficiently different to the rates of apoptosis induced by the noncarcinogenic hepatoproliferators. The results emphasize the importance of considering necrotic reactions from effects on apoptosis in detecting non genotoxic carcinogens. PMID- 11758826 TI - Role of cyclooxygenase-2 in gastric mucosal defense. AB - Two isoenzymes of cyclooxygenase (COX), the key enzyme in prostaglandin (PG) biosynthesis, COX-1 and COX-2, have been identified. COX-1 was proposed to regulate physiological functions, COX-2 to mediate pathophysiological reactions such as inflammation. In particular, it was suggested that maintenance of gastric mucosal integrity relies exclusively on COX-1. Recently, it was shown that a selective COX-1 inhibitor does not damage the mucosa in the healthy rat stomach, although mucosal prostaglandin formation is near-maximally suppressed. However, concurrent treatment with a COX-1 and a COX-2 inhibitor induces severe gastric damage. This indicates that in normal mucosa both COX-1 and COX-2 have to be inhibited to evoke ulcerogenic effects. In the acid-challenged rat stomach inhibition of COX-1 alone is associated with dose-dependent injury which is aggravated by additional inhibition of COX-2 activity or prevention of acid induced up-regulation of COX-2 expression by dexamethasone. After acid exposure, COX-2 inhibitors cause substantial gastric injury when nitric oxide formation is suppressed or afferent nerves are defunctionalized. Ischemia-reperfusion of the gastric artery increases levels of COX-2 but not COX-1 mRNA. COX-2 inhibitors or dexamethasone aggravate ischemia-reperfusion-induced mucosal damage up to 4-fold, an effect abolished by concurrent administration of 16,16-dimethyl-PGE2. Furthermore, the protective effects elicited by a mild irritant or intragastric peptone perfusion are antagonized by COX-2 inhibitors. Finally, COX-2 expression is increased in experimental ulcers. COX-2 inhibitors delay the healing of chronic gastric ulcers in experimental animals and decrease epithelial cell proliferation, angiogenesis and maturation of the granulation tissue to the same extent as non-steroidal anti-inflammatory drugs. These observations indicate that, in contrast to the initial concept, COX-2 plays an important role in gastric mucosal defense. PMID- 11758827 TI - In vitro evidence for matrix regulation of intestinal epithelial biology during mucosal healing. AB - We now know that restitution is more than a process of dedifferentiation and random cell movement across a wound defect. In fact, it is an orderly and regulated process in which gut mucosal epithelial cells adopt a migratory phenotype involving alterations in the cytoskeleton and intracellular motors likely to be tightly regulated by integrin-associated signal proteins and downstream second messengers. The extracellular matrix influences restitution not only as a physical substrate but also by modulating the expression, organization, and activation of the relevant intracellular proteins, as well as by modulating the expression and organization of receptors for soluble factors in the extracellular environment which also influence cell motility. The additional potential avenue of mechanicochemical signaling initiated by cytoskeletal rearrangement awaits further investigation. PMID- 11758828 TI - Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa: relevance of MKP 1, c-fos, c-myc, and cyclin D1 expression. AB - Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Our previous study demonstrated increased ERK activation and MAP kinase phosphatase-1 (MKP-1) overexpression in PHT gastric mucosa. However, it remains unknown which tyrosine kinase receptors are involved in ERK activation and whether ERK activation results in increased cell proliferation. We examined whether EGF receptor (EGF-R) is involved in ERK activation and whether ERK activation triggers epithelial proliferation in PHT gastric mucosa. In gastric mucosa of PHT and sham-operated (SO) rats we studied: (1) EGF-R mRNA and protein expression as well as phosphorylation and membrane protein tyrosine kinase (PTK) activity; (2) ERK2 phosphorylation and activity; (3) MKP-1 mRNA and protein; (4) c-fos, c-myc and cyclin D1 mRNAs, and gastric epithelial proliferation. In PHT gastric mucosa: (1) EGF-R mRNA, protein and phosphorylation and membrane PTK activity were all significantly increased by 38%, 49%, 43% and 49%, respectively; (2) ERK2 phosphorylation and activity were significantly increased by 40% and 50 %, respectively; (3) MKP-1 mRNA and protein expression were significantly increased by 27% and 34%, respectively. In contrast, (4) c-fos, c-myc, and cyclin D1 mRNAs expression were all significantly decreased in PHT gastric mucosa by 36%, 33%, and 49%, respectively, and cell proliferation was significantly lower that in SO rats (11% in PHT vs. 18% in SO). These results suggest that in PHT gastric mucosa, ERK activation is mediated through EGF-R upregulation, but the gastric epithelial proliferation is impaired, possibly by MKP-1 overexpression, leading to reduction of c-fos, c-myc and cyclin D1. PMID- 11758829 TI - Activation of hypoxia inducible factor-1alpha in gastric mucosa in response to ethanol injury: a trigger for angiogenesis? AB - Gastric mucosal injury triggers angiogenesis and activation of VEGF expression, but the mechanism(s) of VEGF gene activation are not known. In some tissues (e.g. myocardium), hypoxia triggers activation of hypoxia-inducible factor-1alpha (HIF 1alpha), a transcription factor known to activate VEGF gene expression. This study was aimed to determine whether hypoxia and/or alcohol injury may induces HIF-1alpha in gastric mucosa. Normal rat gastric tissue was incubated in organ culture under either hypoxic or normoxic conditions for 6hrs. Rats received, intragastrically, either saline or alcohol and gastric mucosa bordering necrosis was obtained at 1-24hrs. HIF-1alpha mRNA and protein were determined by RT-PCR and Western-blot analysis. HIF-1alpha and VEGF proteins were localized by immunostaining. Incubation of normal gastric mucosa under hypoxia caused a significant elevation of HIF-1alpha mRNA (20+/-2%, p<0.05) and protein (262+/ 15%, p<0.005) vs. normoxia. Following alcohol injury, gastric mucosa bordering necrosis demonstrated a significant increase in HIF-1alpha mRNA at 3 and 6hrs (40+/-4%, 19+/-2%; p<0.05), and protein (>300+/-16%; p<0.02 at all time points; highest at 1-3hrs). HIF-1alpha signal was detected in regenerating mucosal microvessels, where it co-localized with VEGF. Since HIF-1alpha initiates transcription of VEGF mRNA, HIF-1alpha activation by ethanol-induced injury is likely responsible for activation of VEGF gene and induction of angiogenesis. PMID- 11758830 TI - MAPK (ERK2) kinase--a key target for NSAIDs-induced inhibition of gastric cancer cell proliferation and growth. AB - Limited clinical and experimental studies indicate that nonsteroidal anti inflammatory drugs (NSAIDs) may inhibit gastric cancer growth. However, the mechanisms involved are not completely understood and cannot be explained by COX 2 inhibition alone. MAPK signaling pathway is essential for cell proliferation, but the effect of NSAIDs on MAPK activity and phosphorylation in gastric cancer has never been studied. Since increased and unregulated cell proliferation and reduced cell apoptosis are important features of cancer growth, we studied whether NS-398, a selective COX-2 inhibitor and/ or indomethacin (IND), a non selective NSAID: 1) inhibit gastric cancer cell proliferation, 2) whether this inhibition is mediated via MAPK (ERK2), and 3) whether NSAIDs enhance apoptosis in gastric cancer cells. Human gastric epithelial cells (MKN28) derived from gastric tubular adenocarcinoma were cultured and treated with either vehicle, IND (0.25-0.5mM) or NS-398 (50-100 microM) for 6, 16, 24 and 48h. STUDIES: 1) Cellular proliferation was determined by 3H-thymidine uptake. 2) MAPK activity was measured by incorporation of radiolabeled phosphate into myelin basic protein. 3) Apoptosis was evaluated using TUNEL assay. IND and NS-398 significantly inhibited the proliferation of MKN28 cells at 24h by 3.5 - 5 fold (p<0.002) and at 48h by 2.5 - 10 fold (p<0.02). Both NSAIDs also significantly inhibited ERK2 activity: IND >53% inhibition, NS-398, 100 microM >72% inhibition; all p<0.05. Both IND and NS-398 significantly increased apoptotic index. In conclusion, IND and NS-398 significantly inhibit proliferation and growth of human gastric cancer cell line MKN28. This effect is mediated by NSAID-induced inhibition of MAPK (ERK2) kinase signaling pathway, essential for cell proliferation. NSAIDs also increase apoptosis in MKN28 cells. In addition to inhibiting cyclooxygenase, NSAIDs inhibit phosphorylating enzymes--kinases essential for signaling cell proliferation. PMID- 11758831 TI - Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signaling. AB - Re-epithelialization is essential for gastrointestinal ulcer and cutaneous wound healing. It requires epithelial cell migration and proliferation, processes that are stimulated by epidermal growth factor (EGF), and dependent on the cell cytoskeleton. Activation of Src and focal adhesion kinase (FAK) has been implicated in EGF-stimulated cell migration. Nonsteroidal anti-inflammatory drugs (NSAIDs) (both nonselective and Cox2-selective) interfere with ulcer healing and re-epithelialization in vitro and in vivo, but the cellular targets and mechanisms remain unexplored forming the basis of this study. Using a wounded gastric epithelial cell monolayer model, we demonstrated that NSAIDs reduce both basal and epidermal growth factor (EGF)-induced re-epithelialization, and that this action involves disruption of actin stress fiber formation, reduced c-Src activity, decreased phosphorylation of focal adhesion kinase (FAK), tensin and their cellular re-distribution. There was a strong correlation between NSAIDs mediated inhibitory effect on re-epithelialization and loss of stress fibers and reduced tensin signal. Furthermore, NSAIDs significantly reduced EGF-stimulated c Src association with FAK. These findings suggest that NSAIDs can directly affect the cell cytoskeleton and signaling pathways essential for re-epithelialization. PMID- 11758832 TI - Integrated duodenal protective response to acid. AB - The proximal duodenum is unique in that it is the only leaky epithelium regularly exposed to concentrated gastric acid. To prevent injury from occurring, numerous duodenal defense mechanisms have evolved. The most studied is bicarbonate secretion, which is presumed to neutralize luminal acid. Less well studied in their protective roles are the mucus gel layer and blood flow. Measuring duodenal epithelial intracellular pH [pHi], blood flow and mucus gel thickness (MGT), we studied duodenal defense mechanisms in vivo so as to more fully understand the mucosal response to luminal acid. Exposure of the mucosa to physiologic acid solutions promptly lowered pHi, followed by recovery after acid was removed, indicating that acid at physiologic concentrations readily diffuses into, but does not damage duodenal epithelial cells. Cellular acid then exits the cell via an amiloride-inhibitable process, presumably sodium-proton exchange (NHE). MGT and blood flow increase promptly during acid perfusion; both decrease after acid challenge and are inhibited by vanilloid receptor antagonists or by sensory afferent denervation. Bicarbonate secretion is not affected by acid superfusion but increases after challenge. Inhibition of cellular base loading lowers pHi, whereas inhibition of apical base extrusion alkalinizes pHi. These observations support the following hypothesis: luminal acid diffuses into the epithelial cells, lowering pHi. Acidic pHi increases the activity of a basolateral NHE, acidifying the submucosal space and increasing cellular base loading. The acidic submucosal space activates capsaicin receptors on afferent nerves, increasing MGT and blood flow. With concontinued acid exposure, a new steady state with thickened mucus gel, increased blood flow, and a higher cellular buffering power protects against acid injury. After acid challenge, mucus secretion decreases, blood flow slows, and pHi returns to normal, the latter occurring via apical bicarbonate extrusion, increasing bicarbonate secretion. Through these integrated mechanisms, the epithelial cells are protected from damage due to repeated pulses of concentrated gastric acid. PMID- 11758833 TI - The role of cellular migration in the repair process of gastric epithelial cells. AB - The epithelial cells of stomach are continuously exposed to various toxic agents that may cause mucosal injury. The epithelial lining is rapidly replaced by cells that migrate from the proliferative zone of the gastric gland, to maintain the integrity of the gastric mucosa. Thus, cell migration is an essential part of the early process of gastric mucosal repair. After various forms of gastric injury, mucosal integrity is reestablished by the rapid migration of epithelial cells. However, the cellular mechanisms of the restitution remain unclear to date. In this report, we will review the role of cellular migration in the repair process of gastric epithelial cells in culture. It has been reported that hepatocyte growth factor (HGF) has the potency of acceleration of cellular repair process. In this review, we also report that HGF plays a leading role in the mucosal repair after damage by using a novel cell culture model. PMID- 11758834 TI - Role of calcium homeostasis in gastric mucosal injury and protection. AB - Using a human gastric mucosal cell line, known as AGS cells, we determined the role that perturbations in intracellular Ca2+ concentration [Ca2+]i might play in cellular injury induced by various damaging agents. For deoxycholate (CD) and ethanol (EtOH) induced damage, a concentration related increase in [Ca2+]i was noted that preceded and closely paralleled the magnitude of injury. Thus, the higher the concentration of DC or EtOH, the more profound were the changes in [Ca2+]i and the resultant degree of cellular injury. Pretreatment with a low concentration of DC (50 microM; called a mild irritant) that was not damaging by itself attenuated injury induced by a damaging concentration (i.e. 250 microM) of DC, and appeared to elicit this protective action through mechanisms that resisted intracellular Ca2+ accumulation. Additional studies indicated that the mechanism of aspirin damage may be similar and that other protective agents such as prostaglandins and growth factors appear to mediate their protective properties through prevention of intracellular Ca2+ alterations. We propose that agents that prevent mucosal injury mediate this activity through a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation. PMID- 11758835 TI - Mechanisms of action of retinoids in gastrointestinal mucosal protection in animals, human healthy subjects and patients. AB - Retinoids prevent chemically induced gastric mucosal damage without inhibiting gastric acid secretion ("nutritional gastric cytoprotection"). The gastroprotective effects of retinoids do not depend on 1) vitamin A activity; 2) number of unsaturated double bonds; 3) the presence of a characteristic chemical structure of their terminal components; however, they depend on 1) intact vagal nerve and 2) adrenals in experimental animals. The gastric cytoprotective effect of retinoids produces a dose-dependent inhibition of ATP-transformation into ADP. It also increases the transformation of ATP into cAMP. Other features of these gastric cytoprotective effects of retinoids include: 1) The retinoid-induced gastric mucosal protection differs from that of PGs; 2) The cAMP is an intracellular signal in the development of gastric mucosal damage produced by chemicals (e.g., ethanol, HCl, indomethacin) and in the protection of gastric mucosa induced by retinoids (but not by PGs); 3) The gastric mucosal protection induced by retinoids and gastric mucosal permeability can be separated in time. The existence of gastric mucosal protection can be demonstrated in healthy persons (against indomethacin treatment), in patients with gastric ulcer (GU) and duodenal ulcer (DU) without any inhibition of gastric acid secretion. The serum levels of vitamin A and zeaxanthin were significantly decreased in patients with chronic gastrointestinal (GI) inflammatory diseases (e.g., terminal ileitis, ulcerative colitis), colorectal polyposis, and different (e.g., esophageal, gastric, pancreatic, hepatocellular and colorectal) malignant diseases. The serum levels of vitamin A provitamins were unchanged and their GI mucosal protective effects do not depend on vitamin A activity. CONCLUSIONS: 1) Abundant experimental and human observations clearly proved the defensive role of retinoids in the GI tract; 2) There is a correlation between the a) scavenger properties of retinoids vs. intact vagal nerve; b) scavenging properties vs. intact adrenals. 3) The GI mucosal protective effect of retinoids is correlated with biochemical changes in the GI mucosa. PMID- 11758836 TI - Modulation of heme oxygenase in tissue injury and its implication in protection against gastrointestinal diseases. AB - Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). There are three isoforms of HO: HO-1 is highly inducible, whereas HO-2 and HO-3 are constitutively expressed. In addition to heme, a variety of nonheme compounds, including heavy metals, cytokines, endotoxins and heat shock stress are strong inducers of HO-1 expression. Many studies indicated that induction of HO-1 is associated with a protective response due to the removal of free heme, which is shown to be toxic. However, recent studies demonstrated that the expression of HO 1 in response to different inflammatory mediators could contribute in part to the resolution of inflammation and have protective effects on brain, liver, kidney and lung against injuries. These beneficial effects seem to be due to the production of bile pigment biliverdin and bilirubin that is a potent antioxidant, as well as the release of iron and CO. However, there are few studies concerning the relationship between HO-1 and inflammation as well as injury in the gut. Interestingly, a preliminary study implicated that induction of HO-1 expression in a colonic damage model induced by trinitrobenzene sulfonic acid played a critical protective role, indicating that activation of HO-1 could act as a natural defensive mechanism to alleviate inflammation and tissue injury in the gastrointestinal tract. PMID- 11758837 TI - Experimental colitis decreases rat jejunal amino acid absorption: role of capsaicin sensitive primary afferents. AB - Ulcerative colitis and experimental colitis are known to be associated with functional and structural abnormalities of the small intestine. The aim of this study was to determine whether experimental colitis in the rat has any effect on jejunal amino acid absorption and to investigate the neural mechanisms involved. In Sprague Dawley rats, colitis was induced by intracolonic administration of 0.1 ml of 6% iodoacetamide. Alanine absorption in the jejunum was measured using the single pass intraluminal perfusion technique in vivo and the three-compartment model in vitro. Experiments were done in normal and sham treated rats, as well as in rats that underwent neonatal capsaicin treatment, adult capsaicin treatment, or subdiaphragmatic vagotomy. Colitis was more severe in rats subjected to neonatal or adult capsaicin treatment, but was not affected by subdiaphragmatic vagotomy. In rats with colitis, jejunal alanine absorption was reduced by 2% (P>0.05), 28%, 40%, and 18% (P<0.001) at 1, 1.5, 2, and 3 days post rectal iodoacetamide administration. A rebound increase of 12% above baseline was noted at 4 days (P<0.05). Similar results were noted in vitro. In rats that received two consecutive injections of iodoacetamide, the decrease in jejunal alanine absorption occurred earlier, was more severe, and persisted for more than 30 days. Neonatal as well as adult capsaicin treatment aggravated both the colitis and the decrease in jejunal alanine absorption. On the other hand, subdiaphragmatic vagotomy attenuated the decrease in jejunal alanine absorption, but had no significant effect on colitis severity. It is concluded that iodoacetamide induced colitis impairs jejunal amino acid absorption and that this effect involves vagal efferents as well as capsaicin sensitive primary afferents. PMID- 11758838 TI - Incidence of diabetes mellitus type 1 in children of southern Thailand. AB - The study was aimed to determine the incidence of diabetes mellitus in children under fifteen years old in southern Thailand. The data of newly diagnosed diabetic patients from 1992 to 1996 were collected by questionaire. The incidence of diabetes mellitus type 1 was 0.52/100,000 population under fifteen years old. There was an increasing trend of this disease over the study period. The peak incidence occurred in the age group 11-15 years. It was more common in females than males. PMID- 11758839 TI - Corneal abnormalities in diabetes. AB - OBJECTIVE: To compare corneal thickness and endothelial morphology in patients with diabetes mellitus and age-matched normal subjects, and to determine whether the duration of diabetes mellitus, severity of diabetic retinopathy, and glycemic control are correlated with these measurements. DESIGN: Single center, case control study. PARTICIPANTS: Sixty eyes of thirty diabetic patients and sixty eyes of thirty healthy nondiabetic subjects were studied. INTERVENTION: Corneal thickness was measured by ultrasonic pachymeter. Corneal endothelial morphology was examined with a contact specular microscope. MAIN OUTCOME MEASURES: Corneal endothelial cell density, mean,cell area, coefficient of variation, percentages of hexagonal cells, and corneal thickness were measured. RESULTS: There was statistically significant increased corneal endothelial cell density and decreased mean endothelial cell area in the diabetic patients. The diabetic corneas had an increased coefficient of variation of endothelial cell area, a decreased percentage of hexagonal endothelial cell and an increased corneal thickness compared with the control subjects, but these differences were not statistically significant. The duration of diabetes mellitus was significantly correlated with pleomorphism, polymegathism and corneal thickness. Severity of diabetic retinopathy was correlated with endothelial cell density, but these correlations were low. The corneal changes were not correlated with glycemic control. CONCLUSIONS: The diabetic corneas tended to be thicker and had more pleomorphism and polymegathism, though this was not statistically significant. Duration of diabetes mellitus correlated significantly with these corneal changes. This suggests that corneal changes should be evaluated and confirmed before intraocular surgery in chronic diabetic patients. PMID- 11758841 TI - Lactose intolerance and intestinal villi morphology in Thai people. AB - OBJECTIVE: To study the relationship of lactose intolerance and intestinal villi morphology in Thai people. MATERIAL AND METHOD: Subjects for this study were patients with functional dyspepsia who had no history of milk allergy and underwent gastroduodenoscopy. Two mucosal biopsy specimens were taken from beyond the distal end of the second part of the duodenum. The specimens were carefully orientated and were graded according to the following scheme: group I: finger shaped villi; group II: mixed finger and leaf shaped villi; group III: clubbing or blunting shaped villi. All subjects were tested for lactose malabsorption by breath hydrogen analysis after consuming 50 gram lactose. Breath hydrogen concentration was analyzed in samples collected intermittently by end-expiratory technique. A rise in breath hydrogen concentration of 20 PPM over baseline was considered evidence of lactose malabsorption. RESULTS: The twenty-five subjects were twenty females (80.0%) and five males (20.0%) who ranged in age from 18 to 53 years (mean 31 +/- 8.29). Sixteen subjects belonged to the finger shaped villi group (64.0%), five to the mixed finger and leaf shaped villi, group (20.0%) and four to the clubbing or blunting shaped villi group (16.0%). Results of breath hydrogen excretion test identified the prevalence of lactose intolerance in 68 per cent of the subjects: 15/16 (93.75%) of group I; 1/5 (20.0%) of group II and 1/4 (25%) of group III respectively (P<0.001). The symptom of diarrhea after lactose loading was correlated well in patients who had positive breath hydrogen analysis. CONCLUSION: As shown in this study, the lactose intolerance is not related to intestinal villi morphology. It is implied that primary lactase deficiency is more common in Thai people than secondary lactase deficiency. PMID- 11758840 TI - Pediatric kidney transplantation: Siriraj Hospital experience. AB - We reported six children with end stage renal disease (ESRD) who received kidney transplantation in our unit from 1996 to 2000. They were 5 boys and 1 girl and their mean age was 9.7 +/- 2.7 years (range 6.8 to 13.2). Etiologies of ESRD were congenital anomalies (3 patients), chronic glomerulonephritis (2 patients), and rapidly progressive glomerulonephritis (1 patient). Prior to the transplantation, chronic peritoneal dialysis was used in 5 patients, including one who had to switch to hemodialysis due to chronic exit site infection and 1 had preemptive kidney transplantation. All children received a kidney from living-related donors, 4 from their fathers, 1 from his mother, and 1 from his elder brother. Triple immunosuppressive drug therapy (prednisolone, azathioprine, and cyclosporine A) was initially given to all patients. Serum creatinine returned to normal within the first week in all patients and 4 patients were discharged home by the end of the second week post operation. Immediate complications included severe hypertension (all patients), ureteral leakage (2 patients), neutropenia (3 patients) and nephrotic syndrome (1 patient). Azathioprine was discontinued in 2 patients due to persistent neutropenia. Cyclosporine A was discontinued in 1 patient due to hepatotoxicity, this patient was maintained on mycophenolate mofetil and prednisolone. Serum creatinine levels at last follow-up (mean 24.3 +/ 19.0 months, range 8-55) were normal in 5 patients and slightly increased (1.5 mg/dl) in one. Five patients returned to school full time within 1 year after kidney transplantation. Height standard deviation score improved markedly as early as 6 months post transplant. The cost of maintenance of the immunosuppressive drugs was similar to adults, i.e. 6,859.1 +/- 1,151.8 Baht per month at 6 months post kidney transplantation. We concluded that kidney transplantation can be performed successfully in selected Thai children with very good results and similar cost of treatment as for adults. PMID- 11758842 TI - Defecography in patients with anorectal disorders: a study in 27 cases. AB - Defecography of twenty-seven cases of anorectal disorders with an age range from 22 to 86 years, were evaluated from June 1989 to February 1999. There were 24 patients with constipation, 2 patients with incomplete defecation and mucous bloody stool in one case. The defecographic results were analyzed regarding the following 1) anorectal angle, defined both at rest and straining 2) abnormalities of the rectal configuration during straining, including rectocele, intussusception, infolding and ulceration. 3) pelvic floor descent. The results showed abnormal anorectal angle 5 cases, rectocele 15 cases, intussusception of the rectal wall 3 cases, infolding 11 cases, ulceration 7 cases and anal canal constriction 1 case. Consequently, the patients with anorectal disorders were found to have a variety of rectal abnormalities in which the defecography would be the imaging tool in demonstrating them. PMID- 11758843 TI - Length of surgical intensive care unit stay and risk factors. AB - OBJECTIVE: To assess length of stay of patients in the surgical intensive care unit (ICU) and to determine risk factors for a long ICU stay. DESIGN: Review of retrospective data. SETTING: University hospital surgical ICU. PATIENTS: Out of a total of 681 admissions to the surgical ICU during a one year period (July 1, 1996 - June 30, 1997), 613 had complete medical data which were analysed. MEASUREMENTS AND MAIN RESULTS: The frequency distribution was skewed to the right. The median and mode were the same (2 days). 35.89 per cent of the ICU admissions had a long stay (>2 days). Independent risk factors for a long ICU stay in the multivariate logistic regression analysis are increasing age, unstable condition, long weaning time, diuretic therapy and re-operation. CONCLUSION: Knowing the length of ICU stay, risk factors for a long ICU stay and how to shorten the ICU stay have potential application in optimizing ICU resource planning and decreasing the health care cost. PMID- 11758844 TI - Gentamicin in neonatal infection: once versus twice daily dosage. AB - Fifty-four neonates were included and completed the study. Twenty-seven neonates were given 2.0-2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0-5.0 mg/kg of gentamicin once daily. The twice daily dose and the once daily dose group had mean steady state gentamicin peak concentrations of 5.94 +/- 1.57 mg/l and 8.92 +/- 1.59 mg/l, respectively (p<0.05) while their trough concentrations were 1.44 +/- 0.49 mg/l and 0.90 +/- 0.35 mg/l, respectively (p<0.05). There were 3 neonates (11.11%) in the twice daily dose group whose peak and trough level were not within the desirable therapeutic range, two patients with too high trough level (>2 mg/l) and one with subtherapeutic peak level (<4 mg/l). Only one patient in the once daily group had undesirable trough level that was higher than 1.5 mg/l but less than 2 mg/l. Treatment with a once daily dose did not present more nephrotoxity than a twice daily dose regimen and had the tendency to have less effect on renal function. Once daily dosage can achieve the equivalent efficacy compared to a twice-daily dosage regimen. All neonates in twice daily and once daily dosage groups showed improvement in clinical outcome. Therefore, a once daily dose of gentamicin with 4.0-5.0 mg/kg could be an appropriate regimen in term neonates during the first 7 days of life. This regimen produces peak concentration that may have greater clinical efficacy and trough concentration with less toxicity than conventional dosing regimen. PMID- 11758845 TI - Endoscopic septoplasty. AB - A retrospective study of endoscopic septoplasties in 28 cases was reviewed to assess the role of endoscopic technique in nasal septal surgery. The results of endoscopic septoplasties had the favorable outcomes and several attractive advantages. PMID- 11758846 TI - Risk factors for stress urinary incontinence in middle aged and elderly Thai women. AB - OBJECTIVE: To determine risk factors of stress urinary incontinence in middle aged and elderly Thai women. MATERIAL AND METHOD: Between March 1999 and January 2000, 46 women with stress urinary incontinence (SUI) with the mean age of 49.05 years old and 168 continent women with the mean age of 49.05 years old were interviewed. The risk factors (e.g. cigarette smoking, childbirth, menopausal status, family history, previous abdominal hysterectomy, transvaginal surgery and body mass index) were studied. The Chi Square or Fisher exact test were used for statistical analysis and p<0.05 was considered as a level of statistical significance. Odds Ratio (O.R.) and its 95 per cent confidence of interval was calculated. RESULTS: The study suggested that menopausal status, childbirth, previous abdominal hysterectomy, transvaginal surgery and family history had no correlation with SUI. The risk factor of body mass index (BMI) > or = Kg/m2 had statistical correlation with SUI. (p=0.000, O.R.=3.570, 95% C.I. of O.R.=1.779 to 7.163). No smokers were found among the studied group so this factor could not be evaluated. CONCLUSIONS: Body mass index was the only identified risk factor of SUI in middle aged and elderly Thai women. PMID- 11758847 TI - Interstitial laser coagulation for the treatment of benign prostatic hyperplasia: a 3 year-follow-up of 30 cases. AB - OBJECTIVE: To report the results and 3 year-follow-up of treatment of benign prostatic hyperplasia (BPH) using interstitial laser coagulation. MATERIAL AND METHOD: Thirty men with BPH underwent treatment with interstitial laser coagulation between December 1996 and April 1997. Their average age was 68 years old. All of them were assessed prior to the treatment and post treatment for symptoms score, uroflowmetry and postvoid residual urine. Any complication and consequence were evaluated at each follow-up visit. RESULTS: Up to 36 months follow-up, all parameters showed marked improvement. The symptom score decreased from 20 to 5. Peak flow rate increased from 4 ml/sec to 17 ml/sec. Residual urine decreased from 115 ml to 8 ml. No major complication was detected. Urethral catheter or intermittent catheterization were used for the mean of 9.1 days. All of the patients who were potent prior to the treatment remained potent and 75 per cent still had prograde ejaculation. No re-treatment was needed in the 3 year follow-up. CONCLUSION: On the basis of these results, we propose that interstitial laser coagulation appears to be a minimally invasive treatment for BPH, with substantial improvement of both objective and subjective parameters. PMID- 11758848 TI - The heme iron content of urban and rural Thai diets. AB - This study aimed to investigate the total iron and heme iron in animal foods, and calculate the heme iron content in urban and rural Thai diets. The samples included land animals and their products (meat, visceral tissue, blood curd and others), fish as well as other aquatic and marine animals. All samples were collected from 3 randomly selected markets located in Bangkok and its vicinity. Analysis of heme iron from foods was done by Han's method. The results showed the mean heme iron in the animal foods was in the range of 17.43-80.83 per cent of total iron. The highest mean heme iron was in the blood curd group and the lowest mean heme iron content was in the fish group. Based on the average amounts of animal food groups consumed per capita/day in the Thai diet which appeared in the Fourth National Nutrition Survey in Thailand (1995), the heme iron content in urban and rural diet was calculated. It was found that the animal iron in the urban and rural diets was 15 per cent and 13 per cent of total dietary iron. Only 7 per cent and 5 per cent of total dietary iron were present as heme iron. The proportion of heme content to total iron derived from animals in the urban diet was 44 per cent. This finding was higher than the estimated value of 40 per cent originally suggested by the Monsen Model. However, in the rural diet, this proportion was 41 per cent which was slightly higher than the suggested estimation. PMID- 11758849 TI - Serological study of Toxoplasma gondii in kidney recipients. AB - Toxoplasma gondii IgG antibodies were determined in 200 kidney recipients by the Sabin-Felmand dye test. Twenty-two (11%) cases were positive for antibody detection. There was a statistically significant difference in the history of taking under-cooked meat, between the number of sero-positive cases and that of sero-negative subjects (63.6% vs 28.8%, p = 0.02). No such significant difference was evident regarding cat ownership (13.6% vs 22.0%, p = 0.3). Sixteen (72.6%) of the 22 subjects with positive Tgondii antibody had undergone kidney transplantation less than one year ago during which a high dose of immunosuppressive drugs were prescribed. The remaining six (27.3%) cases had had transplantation more than one year ago and were on a lower dosage of immunosuprresants. Toxoplasma reactivation seemed to be higher in the former group, which should thus be closely followed-up. Preventive chemoprophylaxis should be considered if there is any indication of toxoplasma reactivation. Since there have been occasional reports of donor-to-host transmission of toxoplasmosis in kidney transplant recipients, serological screening of toxoplasma antibody in kidney donors is advisable. Potential donors with positive toxoplasma antibody should be rejected; but if that is unavoidable, 6-week prophylactic treatment of primary infection in kidney recipients should be administered. PMID- 11758850 TI - Uracil with ftorafur and low dose oral folinic acid in advanced colorectal cancer. AB - BACKGROUND: Low dose oral Folinic acid was used together with uracil with ftorafur (UFT) producing some response with low toxicity in advanced colorectal cancer. However, the 28 day regimen produced 20 per cent severe (grade III, IV) diarrhea. This study required 21 days' treatment to evaluate the response rate and toxicity in advanced colorectal cancer. METHOD: UFT 300 mg/m2/day together with oral Folinic acid 7.5 mg/dose for 21 days with 7 days rest were required to treat 28 cases of recurrent or metastatic colorectal cancer. RESULTS: Partial response was seen in 13.6 per cent of 22 evaluable cases and minimal response seen in 18.2 per cent. The majority (77%) of these patients had previously been treated with 5-fluorouracil (5-FU). These results are comparable to other studies. Toxicity was low with 3.3 per cent grade III, IV diarrhea. CONCLUSION: This regimen produced some activity in metastatic colorectal cancer with low toxicity. PMID- 11758851 TI - Ejaculatory duct obstruction in the infertile male: experience of 7 cases at Ramathibodi Hospital. AB - OBJECTIVE: To study the clinical presentations, management, outcomes as well as pregnancy rate of ejaculatory duct obstruction treated at the Division of Urology, Ramathibodi Hospital. MATERIAL AND METHOD: This retrospective study was done from 1980 to 1999 and information from the medical records of the patients of ejaculatory duct obstruction was obtained. Phone and mail were used for long term follow-up. RESULTS: Seven male patients with ejaculatory duct obstruction were identified. The age ranged from 32-45 years old (mean 34.5). All of the patients had azoospermia without other symptoms related to ejaculatory duct obstruction such as painful ejaculation, perineal or testicular pain. Normal testicles and secondary sex characteristics were noted in all. Seventy-one per cent had normal hormonal profiles and twenty-nine per cent had a slight increase of FSH, LH but not more than one fold of normal range. Vasography was used as the diagnosis tool in all of the cases and 71 per cent of seminal vesicles were >1.5 cm in diameter and all the rest were 1 cm in diameter. Transurethral resection of ejaculatory duct (TURED) was done in 6 cases and transurethral incision of ejaculatory duct (TUIED) was done in 1 case. Semen analysis was done in the third month after operation and 4 of 7 (57%) showed improvement of semen analysis but another 3 cases (43%) still had azoospermia. Six months after operation 6 of 7 (86%) showed improvement of semen analysis. Up to one year, 6 of 7 (86%) have normal semen analysis and another one still had azoospermia. In the long-term follow-up, 4 of 7 (57%) were able to impregnate their wives. CONCLUSIONS: Ejaculatory duct obstruction is a treatable cause of male infertility. In an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes and normal hormonal profiles, ejaculatory duct obstruction is suggested. Transrectal ultrasonography (TRUS) and/or vasography can be done to confirm the dilatation of seminal vesicles and obstruction of the ejaculatory duct. Transurethral resection of the ejaculatory duct (TURED) has resulted in marked improvement in semen parameters, and pregnancies have been achieved. PMID- 11758852 TI - General practice residency training program in Thailand: past, present, and future. AB - The General Practice was approved by the Thai Medical Council as a specialty in 1969. The residency training programs were revised in 1992. The first three - year rotating postgraduate residency training program was started in 1973 with a total of 9 programs by the late 1980s. Seven were in Bangkok, and the other 2 were in the North. The programs contained curricula objectives, clinical rotation in various disciplines including a general practice block in provincial or community hospitals. The weakness of the programs was the lack of a general practice department, a general practice trainer or preceptor and a general practice course organizer. Finally, the General Practitioners Association played a little role in the postgraduate general practice residency. After the revision, the general practice residency was changed to family medicine residency training in 1999. The College of Family Physicians of Thailand was established to take a central role in postgraduate education. PMID- 11758853 TI - Evaluation of ventricular myocardial velocities and heart motion of the fetal heart by tissue Doppler image. AB - Fetal echocardiogram has developed into a reliable tool for prenatal diagnosis of congenital heart disease. It is also used to evaluate ventricular function. Recently, Tissue Doppler Imaging (TDI) has been introduced to evaluate ventricular functions especially in ischaemic heart disease. The objective of this study was to evaluate myocardial velocities and heart motions of the normal fetal heart by using TDI. The TDI was preformed in 28 fetal hearts with a gestational age of 20-35 wks (Mean 29 +/- 3.7 wks) to evaluate myocardial velocities and heart motion. The Toshiba, Power Vision, machine with 3.75 and 5 MHz transducers was used with an appropriate setting of colour-coded tissue velocities. The apical four chamber and apical or parasternal long axis views were the standard planes for measuring myocardial velocities and evaluating the heart motions. The results showed the myocardial velocities of the posterior wall of the left ventricle during the early, mid, and late systolic phases were 1.5 +/ 0.2, 2.1 +/- 0.9, and 1.0+0.5 cm/sec and early, mid, and late diastolic phases were 1.3 +/- 0.7, 1.9 +/- 0.8, and 1.1 +/- 0.7 cm/sec respectively. The myocardial velocity of the anterior wall of the right ventricle during the early, mid, and late systolic phases were 1.7 +/- 0.9, 1.7 +/- 0.6, and 1.0 +/- 0.6 cm/sec and early, mid, and late diastolic phases were 1.1 +/- 0.6, 1.8 +/- 0.7, and 1.5 +/- 1.0 cm/sec respectively. The myocardial velocity of the interventricular septum could not be measured due to the abnormal septal motion and the total fetal heart movement during the cardiac cycle. The fetal heart had anterior displacement during systole and posterior translation during diastole and also had counter-clockwise rotation during the systolic phase. CONCLUSION: Using the TDI to evaluate myocardial velocities of the fetal heart is limited by the angle of ultrasound beam and the total fetal heart motion. The fetal heart movement is similar to the newborn or young adult heart. PMID- 11758854 TI - Reducing the risk: heart disease, stroke and aspirin. AB - Aspirin used in cardiovascular disease is probably the best evaluated and the most highly cost effective prophylactic available in clinical practice today. It has been evaluated in over 150 randomised controlled trials and a small daily dose of around 100 mg has been shown to reduce the risk of myocardial infarction and stroke by about 30 per cent. The saving of lives and prevention of vascular events in patients judged to be at increased risk of a vascular event for any reason is large. In healthy subjects, however, the risk of a vascular event is so low that prophylaxis by any drug is inappropriate. The earlier aspirin is given in the acute phase of a myocardial infarction the greater the saving of lives. Patients judged to be at increased risk of a vascular event, for any reason, should therefore be advised to carry aspirin and to chew and swallow one or two tablets immediately, if they experience sudden severe chest pain. Aspirin is derived from a salicylate, and salicylates are widely distributed in nature, with many functions in plants. Its use in cardiovascular disease derives from an effect on blood platelets, but other possible effects have led to suggestions that it may be of benefit in conditions other than heart disease and stroke. Current research is now focussing on the possible reduction by aspirin in the risk of dementia, certain cancers, retarded foetal growth and cataract. PMID- 11758855 TI - Different mechanism of bone loss in ageing women and men in Khon Kaen Province. AB - The changes of vitamin D status and biochemical markers of bone turnover have been reported with aging. In this study we determined age-related levels of vitamin D and biochemical markers of bone turnover in the general adult population between the ages of 20 and 84 years who were living in Khon Kaen province in northeastern Thailand. Serum 25 hydroxyvitamin D was determined as an indicator of vitamin D status. Serum total alkaline phosphatase and N-terminal mid fragment osteocalcin were measured as biochemical markers of bone formation and serum C-terminal fragment of type I collagen was measured as a marker of bone resorption. The levels of serum 25 hydroxyvitamin D were high in the Khon Kaen population. Men had higher levels of 25 hydroxyvitamin D than did women. However, there were no changes with age in either sex. In women, all biochemical markers of bone turnover increased with age after the fourth decade. The sharp increase was observed in the sixth decade which was around the menopausal age. In contrast, in men all biochemical markers of bone turnover except serum total alkaline phosphatase had a tendency to decrease with age. CONCLUSION: There was no evidence of vitamin D deficiency in a Khon Kaen population. In addition, serum vitamin D levels did not decline with ageing. Women and men showed different changes of biochemical markers of bone turnover with ageing indicating gender difference in the pathogenesis of osteoporosis. PMID- 11758856 TI - Detection of Mycobacterium tuberculosis from sputum collected on filter paper and stored at room temperature for 5 days by PCR assay and culture. AB - The efficacy of PCR assay and culture for direct detection of M. tuberculosis (MTB) from sputum specimens collected on filter paper and stored at room temperature for 5 days was evaluated in comparison with conventional culture of fresh sputum specimen. A total of 231 sputum specimens were examined. MTB was recovered from 124 samples by culture from fresh sputum samples before storage. The culture positivity rate was significantly decreased to 70 per cent after 5 day's storage on filter paper. For PCR assay, a fragment of 377-bp of the IS6110 sequence was amplified and detected using nested PCR. Compared with culture results performed on fresh sputum samples, the sensitivity, specificity, and efficiency for the nested PCR were 96.0, 97.2 and 96.5 per cent, respectively. The nested PCR showed sensitivity and specificity with no significant difference (p>0.05) from culture of fresh sputum specimens. CONCLUSION: The collection and storage of sputum on filter paper at room temperature for 5 days had no apparent effect on the performance of nested PCR. Sputum samples collected by this method could be sent by post in a minimum of space and inexpensive way and will enable a large number of samples collected in the field or from peripheral health centers to be sent to central laboratories for analysis by trained technicians and under a well-equipped and well-established quality control system. The rapid and reliable detection by PCR-based assay will be helpful for optimal patient management of therapy and effective control of tuberculosis. PMID- 11758857 TI - Comparison of embryonic development in cleavage stage mouse embryo biopsy between acid Tyrode's solution and laser assisted techniques. AB - The study was carried out to determine the effectiveness and safety of the infrared 1.48 microm laser in cleavage stage mouse embryo biopsy, compared to the conventional acid Tyrode's solution. One hundred and thirty cryopreserved cleavage stage mouse embryos were included in the study. Fifty embryos were biopsied by acid Tyrode's solution. Forty-seven embryos were biopsied by the infrared 1.48 microm laser. Thirty-three embryos were incubated without biopsy as the control group. Thirteen of 50 embryos in the acid Tyrode's group and 16 of 47 in the laser assisted group became cavitating morulae on day 4, meanwhile 23 of 33 in the control group reached this stage. The blastocyst formation of acid Tyrode's, laser assisted and control group were 94.0, 97.8 and 100.0 per cent, respectively. The hatching rate of acid Tyrode's solution, laser assisted and control group were 78.7, 84.7 and 63.6 per cent, respectively. No significant difference in blastocyst formation and hatching rate was found. The percentage of grade I blastocysts in control group (96.9%) was significantly higher than those in acid Tyrode's solution (68.0%) and the laser assisted group (76.0%). There was no significant difference in the percentage of grade 1 blastocysts between the acid Tyrode's solution and the laser assisted group. In conclusion, the infrared 1.48 microm wavelength laser may be an alternative to acid Tyrode's solution in embryo biopsy. PMID- 11758858 TI - The first world report of botulinum A toxin injection for status migrainosus. AB - The author reports the first ever documented publication in the world concerning the use of botulinum toxin A (BTX-A) injection for status migrainosus. A 58-year old man had been suffering from migraine without aura for 20 years. This last attack (a very severe throbbing headache) started over the left side of his head and he had tried several medications (paracetamol, aspirin, ergotamine, mefenamic acid, and diazepam) during the attack to no vail. Physical examination revealed an acutely ill patient with an agonizing pain condition. General and neurological examinations were normal. BTX-A solution was then injected into the Fung Chou point (classical Chinese acupuncture point for migraine) in the total amount of 25 international unit. Dramatic response was observed within 1 hour of injection and status migrainosus was abort within 10 hours. He was headache-free and had no further attack of migraine for another 2 months. PMID- 11758859 TI - Costs-effectiveness of the urban health center in Nakhon Ratchasima: a case study on diabetes and hypertension. AB - Health care reforms in Thailand are looking for a better health infrastructure within the urban setting. The urban health center is one of the models tried in many provinces. This study compared the costs--effectiveness of the urban health center in Nakhon Ratchsima with the Maharaj Nakhon Ratchasima Hospital, using diabetes and hypertension as tracer conditions. The point estimates by a retrospective review and cross-sectional study revealed that the overall costs (provider plus patient costs) of the urban health center for these tracers were lower than the costs of the Maharaj Hospital. The effectiveness of treatment at the urban health center was also better. It was concluded that the urban health center should be considered as a better alternative of primary care institution within the urban area. PMID- 11758860 TI - Guillain-Barre's syndrome associated with Plasmodium falciparum malaria: role of plasma exchange. AB - Guillain-Barre's syndrome (GBS) associated with malarial infection is a rare condition reported in the literature. We report a case of Plasmodium falciparum (PF) malarial infection with Guillain-Barre's syndrome complicated by respiratory failure and review of the literature. Our patient gradually improved after treatment with plasma exchange. Review of the literature showed 11 cases of GBS associated with malaria. Four of 8 patients with GBS associated with PF had respiratory failure, whereas, none of the patients with GBS associated with Plasmodium vivax (PV) developed respiratory failure. Three of four patients with respiratory failure died and one who survived was treated with intravenous immunoglobulin. Our patient was the second case to survive after treatment with plasma exchange. The role of plasma exchange, the pathogenesis of malaria in GBS and the mechanism that induced more severe GBS in PF than in PV were discussed. PMID- 11758861 TI - Who has the ultimate responsible for publishing clinical research results? PMID- 11758862 TI - Life after a national nightmare: coping with invisible illness and disability. PMID- 11758863 TI - Social workers' role in disease management. AB - This article discusses social work's participation in a new paradigm for health care delivery, disease management. Attempts to improve health care quality havefocused on evidence-based methods of evaluating health care outcomes as well as quality of life issues with which social workers have been traditionally concerned. The fit between social work's ecological perspective and disease management and the needfor social workers to participate as patient case managers on interdisciplinary disease management teams are discussed. Quality and cost benefits can occur when social workers address such issues as adherence, psychosocialfactors, and depression in terms of the patient's global recovery and concurrent enhancement of quality of life. Potential barriers to disease management implementation with social work participation are discussed. PMID- 11758864 TI - A descriptive analysis of older adults with HIV/AIDS in California. AB - Between 10 percent and 15 percent of all AIDS cases throughout the United States have been reported in people ages 50 and over. However, older adults often have been overlooked in research on HIV/AIDS. The study discussed in this article examined 571 individuals ages 30 to 81 who had been diagnosed with symptomatic HIV or AIDS. A cross-sectional analysisfound that those in older age groups were more likely to befemale, to live alone, to have private health insurance, and to have died during the study. The results of the study suggest that social workers need to be aware of and sensitive to the role of sociodemographic factors in the lives of older HIV-infected individuals. PMID- 11758865 TI - Disclosure of HIV status in the workplace: considerations and strategies. AB - Maintaining a role in the workplace despite significant health concerns can be important in meeting an individual's emotional and economic needs. This qualitative research study reviewed the workplace experiences and disclosure decisions of 18 HIV-positive individuals. The most frequently cited reasonsfor disclosing HIV status were to explain choices they were making as they interviewed for a job and concerns about their job performance and the needfor accommodations. For individuals who disclosed their HIV status to selective members of the workplace or disclosed to no one, the primary reasons given were preference for privacy, nature of the work environment, andfear of possible consequences. The practice, policy, and research implications for social workers are also discussed. PMID- 11758866 TI - Health-related worries, self-image, and life outlooks of long-term survivors of childhood cancer. AB - This article poses three questions: what do childhood cancer survivors worry about? What characteristics prompt some to worry more and others less? What effect do worries have on survivors' self-image and life outlooks? Data from 303 survivors of childhood cancer demonstrated significant relationships among worries, "objective" factors like physical after-effects or relapse, and survivors' self-images and life outlooks. However, findings also indicated that subjectively experienced worries, perceptions about one's cancer status, age at diagnosis and gender were more strongly associated with self-image and life outlook. Psychosocial interventions andfuture research are suggested. PMID- 11758867 TI - Family caregiving and traumatic brain injury. AB - This article discusses the extensive challenges faced by those providing long term care for family members with traumatic brain injury. Areas reviewed include the nature of care needs, stress and burden experienced, and how families cope with caregiving demands. This article concludes with a discussion of what social workers can do to reduce the demands of family caregiving and subsequently, improve caregivers' quality of life. PMID- 11758868 TI - The experience of deafened adults: implications for rehabilitative services. AB - This study explored the psychological and social effects of becoming deaf as an adolescent or adult and the adequacy of rehabilitation services offered to such individuals. Qualitative interviews were conducted with a sample of eight deafened adults in the Province of Ontario, Canada. The results indicated that medical interventions (for example, audiometric testing, hearingaidprovision, and cochlear implantation) were relied on exclusively as rehabilitation servicesfor the deafened adults. None of the study participants were referred to individual, family, or group counseling by their physicians or hearing health services providers, despite the many negative effects of becoming deaf that participants described. This gap in service makes it apparent that the rehabilitation system for adventitious deafness needs the involvement of counselors and social workers to better ensure that the psychosocial needs of clients are addressed. PMID- 11758869 TI - Infant mortality: a reflection of the quality of health. PMID- 11758870 TI - Ohio dental association not giving lip service to new smokeless tobacco product. PMID- 11758871 TI - Spectroscopy in prostate cancer: hope or hype? AB - Clinical applications of image-based radiation therapy for the study of prostate cancer have expanded significantly over the past years. The results of recent studies of magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopic imaging (MRSI) demonstrate that the MRI/MRSI exam is a unique method by which to noninvasively study the cellular metabolism and anatomy of the prostate. This technology has the potential to define the tumor volume through functional or metabolic imaging. The results of current MRI/ MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy, as well as the extent of the time course of metabolic changes after therapy, may improve our understanding of cancer aggressiveness. Assessment of cancer spread outside the prostate can be significantly improved by combining MRI findings with estimates of metabolic abnormalities provided by MRSI. Clinically, combined MRI/MRSI has already demonstrated a potential for improved diagnosis, staging, and treatment planning for patients with prostate cancer. Additional studies will reveal both the positive aspects and clinical challenges of MRI/ PMID- 11758872 TI - Neuropathic cancer pain: the role of adjuvant analgesics. AB - Neuropathic pain may be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. This pathophysiologic label is typically applied when the painful symptom is associated with an overt injury to neural structures, is part of a recognized syndrome, or has a dysesthetic quality (usually burning, shooting, or electrical). Most neural injury does not lead to clinically important neuropathic pain, but sometimes even a small degree of tissue injury can precipitate severe pain. In the cancer population, neuropathic pain is often related to compression, direct neoplastic invasion of the peripheral nerves or spinal cord, or to a neuropathy caused by chemotherapy. To manage neuropathic pain in this population, nonopioid adjuvant drugs that are neuroactive or neuromodulatory are often needed to complement opioid therapy. The primary adjuvant analgesics are anticonvulsant and antidepressant medications, but a wide variety of other drugs are also used. To optimize analgesic therapy in patients with neuropathic pain, both opioid and adjuvant analgesics must be used effectively. PMID- 11758873 TI - Clinical trials referral resource. Health-Related quality of life in cancer prevention clinical trials. PMID- 11758874 TI - Molecular markers for diagnosis, staging, and prognosis of bladder cancer. AB - Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and characterize various bladder cancers and their true biological potential more effectively. The need to predict which superficial tumors will recur or progress--and which invasive tumors will metastasize--has led to the identification of a variety of potential prognostic markers for patients with bladder cancer. The molecular changes that occur in transitional cell carcinoma of the bladder are numerous and can be categorized into (1) chromosomal alterations, leading to carcinogenesis; (2) loss of cell-cycle regulation, accounting for cellular proliferation; and (3) growth control events such as angiogenesis, resulting in metastasis. It is becoming apparent that the accumulation of genetic and molecular changes ultimately determines a tumor's phenotype and subsequent clinical behavior. The potential clinical application of new diagnostic techniques (ie, loss-of heterozygosity analysis to identify tumor suppressor genes) and older, well established, techniques (ie, immunohistochemistry) combined with improvements in the use of automated and standardized systems are areas of active investigation. PMID- 11758875 TI - Anemia treatment and the radiation oncologist: optimizing patient outcomes. AB - Anemia is a frequent complication of cancer and its associated treatment. Although its occurrence is well documented in the chemotherapy setting, the prevalence and nature of anemia in the radiation oncology setting have been inadequately characterized. Preliminary findings from an ongoing retrospective study at Beth Israel Medical Center in New York indicate that mild-to-moderate anemia (ie, hemoglobin levels of 10 to 12 g/dL) is common at presentation for radiation therapy and increases in prevalence and severity during the course of radiation treatment. The symptoms of mild-to-moderate anemia, particularly fatigue, can substantially impair the quality of life of cancer patients. Furthermore, an extensive body of literature has documented an association between low hemoglobin levels and poor locoregional tumor control and survival following curative-intent radiation therapy. Greater efforts by radiation oncologists to document and treat anemia in patients undergoing radiation therapy may provide an opportunity to improve postradiation outcomes and well-being. PMID- 11758876 TI - Management of pressure ulcers. AB - Pressure ulcers are a common problem, with about 1.5 to 3 million individuals in the United Stated affected. Treatment may be costly, requiring lengthy periods of hospitalization. Central to the development of pressure ulcers is the loss of the ability of bedridden patients to move spontaneously. When this ability is impaired by neurologic injury or debility, damage caused by unrelieved pressure against tissue trapped between the support surface and a bony prominence becomes evident. Current recommendations for prevention advise providing optimal skin care to those at risk of tissue breakdown. Once a pressure ulcer is diagnosed, an initial assessment, including staging the ulcer and a comprehensive assessment, is required. A treatment plan can then be devised. Planning should include management of tissue loads, ulcer care, and nutritional support. The dogma that all pressure ulcers are caused by poor care should be recognized as incorrect. Even the most exemplary care may not prevent the development of, or heal existing, pressure ulcers in high-risk patients. PMID- 11758877 TI - Preschool and school age children under welfare reform. AB - This study compared the behavioral and school problems of young children whose mothers participated in two different income support programs, Jobs First and AFDC. The analyses also included measures of maternal education, maternal health, maternal psychological factors, and family environment. There were no differences in child school or behavioral problems across the income support programs. Children, however, were more likely to have school problems if they were older or if their mothers received less than a high school education, reported child behavioral problems or made criteria for depression on the CIDI. Behavioral problems were more likely to occur if mothers reported violence in the home, many depressive symptoms on the CES-D, few child positive qualities, or if the child had repeated a grade. Several familial factors, then, must be addressed in order to ensure that children excel both academically and behaviorally. PMID- 11758878 TI - Identifying the psychological needs of foster children. AB - Recent research has pointed to the increased risk of pathology for children placed in foster care. In response, the Child Welfare League of America has advocated for routine assessment of the psychological needs of children in foster care. A model for standardized psychological screening for all foster children shortly after placement is described. Interdisciplinary relationships between medical and psychological staff are stressed. Typical referral questions are outlined and suggestions for a testing battery that covers cognitive, behavioral, and emotional realms are given. Issues and problems inherent in testing this population are discussed, but the importance of psychological screening of this at-risk population is emphasized. PMID- 11758879 TI - Recognition of facial affect by children and adolescents diagnosed with social phobia. AB - This study compared the ability of children with social phobia and children with no psychiatric disorder to accurately judge facial affect. Fifteen children and adolescents with social phobia and 14 control children were asked to identify emotions depicted in slides from the Pictures of Facial Affect. In addition, they rated their level of anxiety on a pictorial Likert scale prior to and upon completion of the facial recognition task. The results indicated that children with social phobia had significantly poorer facial affect recognition skills than normal controls and reported greater anxiety upon completion of the recognition task. Multivariate analysis revealed significant differences between groups in the number of errors based on the type of facial affect. Posthoc analysis indicated that deficits were most pronounced for facial representations of happiness, sadness, and disgust. The results are discussed in relation to an integrated model of social skills training that includes facial affect recognition training as a integral component in treatment programs for children and adolescents with social phobia. Directions for future research with larger samples of more ethnically diverse children and adolescents are presented. PMID- 11758880 TI - The effects of maternal depression on the efficacy of a literacy intervention program. AB - The purpose of the present study was: (1) to determine whether depression was related to mother-child interactions in a group of low-income mothers participating in a literacy intervention; (2) to examine whether depression was related to retention; (3) to determine whether there were differential changes in depressed and nondepressed mothers in the intervention group. Participants included 488 ethnically diverse families. Depressed mothers engaged in fewer literacy enhancing behaviors with their children than non-depressed mothers and were more likely to drop out of the study. Depressed mothers were as likely to participate actively in the intervention, and benefited as much from the intervention as non-depressed mothers. PMID- 11758881 TI - Frontal P300 decrement and executive dysfunction in adolescents with conduct problems. AB - This study investigated the cognitive and cerebral function of adolescents with conduct problems by neuropsychological battery (STIM) and event-related potential (ERP). Eighteen adolescents with conduct disorder, and 18 age-matched normal subjects were included. Such cognitive functions as attention, memory, executive function and problem solving were evaluated using subtests of STIM. ERP was measured using an auditory oddball paradigm. The conduct group showed a significantly lower hit rate on the Wisconsin Card Sorting Test (WCST) than the control group. In addition, the conduct group showed reduced P300 amplitude at Fz and Cz, and prolonged P300 latency at Fz, and there was a significant correlation between P300 amplitude and Stroop test performance. These results indicate that adolescents with conduct problems have impairments of executive function and inhibition, and that these impairments are associated with frontal dysfunction. PMID- 11758882 TI - Research on interbreed ova transfer in pigs. PMID- 11758883 TI - Progress in reproductive biotechnology in swine. AB - This article summarizes recent progress in reproductive biotechnology in swine with special reference to in vitro production of embryos, generation of identical multiples, and transgenic pigs useful for xenotransplantation. In vitro production (in vitro maturation, in vitro fertilization, and in vitro culture) of viable porcine embryos is possible, although with much lower success rates than in cattle. The main problems are insufficient cytoplasmic maturation of porcine oocytes, a high proportion of polyspermic fertilization and a low proportion of blastocysts that, in addition, are characterized by a low number of cells, hampering their development in vivo upon transfer to recipients. Microsurgical bisection of morula and blastocyst stage embryos leads to a 2 to 3% monozygotic twinning rate of the transferred demiembryos, which is similar to that in rabbits and mice but considerably lower than in ruminants. It was found that with decreasing quality an increasing proportion of demi-embryos did not possess an inner cell mass. Porcine individual blastomeres derived from 4- and 8-cell embryos can be cultured in defined medium to the blastocyst stage. Leukemia inhibitory factor has been shown to be effective at defined embryonic stages and supports the formation of the inner cell mass in cultured isolated blastomeres in a concentration-dependent manner. For maintaining pregnancies with micromanipulated porcine embryos, it is not necessary to transfer extraordinarily high numbers of embryos. Porcine nuclear transfer is still struggling from the inefficiency of producing normally functioning blastocysts. Blastomeres, blastocyst-derived cells, fibroblasts and granulosa cells have been employed as donor cells in porcine nuclear transfer and have yielded blastocysts. Recently, the generation of the first piglets from somatic cell nuclear transfer has been achieved. DNA-microinjection into pronuclei of porcine zygotes has reliably resulted in the generation of transgenic pigs, which have special importance for the production of valuable pharmaceutical proteins in milk and xenotransplantation. It has been demonstrated that by expression of human complement regulatory proteins in transgenic pigs the hyperacute rejection response occurring after xenotransplantation can be overcome in a clinically relevant manner. Although biotechnological procedures in swine have recently undergone tremendous progress, the development is still lagging behind that in cattle and sheep. With regard to genetic engineering, considerable progress will originate from the possibility of employing homologous recombination in somatic cell lines and their subsequent use in nuclear transfer. In combination with the increasing knowledge in gene sequences this will allow in the foreseeable future widespread use in the pig industry either for agricultural or biomedical purposes. PMID- 11758884 TI - State of the art in artificial insemination of pigs in the United States. AB - Currently, the United States ranks second in pork production worldwide. In 1999 the breeding herd consisted of approximately 6.2 million breeding females with an annual production of 100 million market animals having an average market live weight of 118.6 kg. The objective of this paper is to briefly describe the current US swine artificial insemination (AI) industry and to profile semen production and insemination practices that are currently in use. PMID- 11758885 TI - Factors influencing the success of embryo transfer in the pig. AB - Progress in reproductive biotechnologies has led to an increased use of embryo transfer in both swine research and swine production. This review article describes the history and subsequent development of porcine embryo transfer. Special attention is given to aspects of the overall process of embryo transfer which are unique to pigs. PMID- 11758886 TI - Recent developments in pig embryo transfer. AB - Porcine embryo transfer has been performed for approximately 50 years, and surgical methods have proven to be reliable for collection and transfer of embryos. However, surgical collection and transfer have the disadvantage of being less useful on the farm. Recently, new procedures for both collection and transfer of embryos have been developed to improve usefulness. The surgical procedure has been refined to a minimally invasive procedure, using endoscopy for collection and transfer of embryos. A nonsurgical procedure for embryo collection has also been devised, but is limited to use in sows with surgically shunted (shortened) uterine horns. Nonsurgical embryo transfer procedures have been developed recently and have proven to be successful. The nonsurgical procedures are preferable to surgical procedures from an animal welfare point of view and because these procedures can be performed on farms without the need for special facilities. PMID- 11758887 TI - Cryopreservation of swine embryos: a chilly past with a vitrifying future. AB - Since the development of embryo freezing technologies for cattle in the 1980s, advances in cryobiology, cell biology and embryology of domestic animals have enabled the development of embryo preservation methodology for the pig, notorious for extreme sensitivity to cooling. This review outlines recent efforts to understand the biology of pig embryos as related to their extreme sensitivity to cooling. Cellular analyses and molecular approaches are discussed that have enabled pig embryos to survive cryopreservation and after transfer develop into live offspring with normal fecundity at maturity. In the near future, use of preserved embryos will be a routine breeding alternative for swine producers, providing: preservation methods for maternal germplasm; global genetic transport; increased selection pressure within herds; breeding line regeneration or proliferation; and methodology for genetic resource rescue. It took almost 50 years after the first successful embryo transfer to develop embryo preservation in the pig. Nonetheless, by applying novel methods described herein, rapid progress has been achieved. PMID- 11758888 TI - Transgenic technology and applications in swine. AB - The introduction of foreign DNA into the genome of livestock and its stable integration into the germ line has been a major technical advance in agriculture. Production of transgenic livestock provides a method to rapidly introduce "new" genes into cattle, swine, sheep and goats without crossbreeding. It is a more extreme methodology, but in essence, not really different from crossbreeding or genetic selection in its result. Several recent developments will profoundly impact the use of transgenic technology in livestock production. These developments are: 1) the ability to isolate and maintain in vitro embryonic stem (ES) cells from preimplantation embryos, embryonic germ (EG) and somatic cells from fetuses; and somatic cells from adults, and 2) the ability to use these embryonic and somatic cells as nuclei donors in nuclear transfer or "cloning" strategies. Cell based (ES, EG, and somatic cells) strategies have several distinct advantages for use in the production of transgenic livestock that cannot be attained using pronuclear injection of DNA. There are many potential applications of transgenic methodology to develop new and improved strains of livestock. Practical applications of transgenesis in livestock production include enhanced prolificacy and reproductive performance, increased feed utilization and growth rate, improved carcass composition, improved milk production and/or composition and increased disease resistance. Development of transgenic farm animals will allow more flexibility in direct genetic manipulation of livestock. PMID- 11758889 TI - Eosinophil chemokines and chemokine receptors: their role in eosinophil accumulation and activation in asthma and potential as therapeutic targets. PMID- 11758890 TI - Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid. AB - We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways. PMID- 11758891 TI - Risk factors for asthma morbidity and mortality in a large metropolitan city. AB - Morbidity and mortality due to asthma continues to increase despite advances in understanding the pathophysiology and treatment of the disease. We evaluated the potential risk factors for asthma morbidity and mortality in a large metropolitan city (St. Louis, MO) using small area geographic analysis. We found that the risk of hospitalization for children with asthma was 8.4 times greater (95% confidence interval [CI] 7.0-9.9) in lower socioeconomic zip code areas and 5.3 times greater (95% CI 4.7-5.9) in those zip codes with a higher percentage of African Americans. Similarly, the risk of death due to asthma was 6.4 times greater in the lower socioeconomic zip code areas (95% CI3.4-12.1). Lower socioeconomic status and African American race are strong risk factors for hospitalization and mortality from asthma. Public policy and healthcare resources need to be organized and directed more efficiently to this population. PMID- 11758892 TI - Level of control and hospital contacts in persistent asthma. AB - The purpose of this study was to estimate relationships between asthma control and hospital contacts (visits to emergency rooms and hospitalizations) in a group of patients suffering from persistent asthma, after adjustment for prior use of inhaled corticosteroids. A computerized family practice database was used to identify patients (aged 6-50 years) with persistent asthma who received asthma therapy from January 1995. The database provided information on patient demographics and drug therapy. Asthma control was estimated by a survey of patients at the end of a 12-month study period. Frequency of hospital contacts during the study period was related to demographics, asthma control, and prescribed doses of inhaled corticosteroids during a prestudy period. Review of computerized medical files of 497 family practice physicians identified 1,966 patients with persistent asthma who met the study criteria. Of these patients, 1,251 completed the survey (63.6%). Asthma control was assessed in 1,130 patients; it was moderate or poor in 42% of the cases. During the 12-month study period, 14.8% of patients reported at least one hospital contact. The level of asthma control was significantly (p < 0.001) associated with hospital contacts. The odds ratio (OR) for hospital contact for good and poor asthma control was 0.5 (95% confidence interval [CI] 0.2-0.7) and 2.2 (95% CI 1.2-4.4), respectively. Asthma control was related to hospital contacts independently of use of inhaled corticosteroids before the study period. Overall, control of asthma was not optimal in this population. The occurrence of hospital contacts was closely related with the level of control. This association was independent of the dose of inhaled corticosteroids prescribed before the study, suggesting that in asthma, hospital contacts are primarily related to the level of control experienced by the patients. PMID- 11758893 TI - The relationship between prescribed and delivered doses of inhaled corticosteroids in adult asthmatics. AB - A model was developed to estimate the impact of adherence and inhalation technique over time on delivered doses of inhaled corticosteroids (ICS) for asthmatics using metered-dose inhalers (MDIs) and dry powder inhalers (DPIs). Factors affecting inhalation technique include ongoing training, inhalation device, spacer use (with MDIs), and natural ability. Model parameters were derived from a literature review or were estimated from clinical experience. Analyses demonstrated that most patients receive a fraction of prescribed ICS doses over time. The model may be used to better understand the impact of increasing ICS dosages and to estimate the likelihood of patients being underdosed. PMID- 11758894 TI - Emergency department use of ketamine in pediatric status asthmaticus. AB - The objective of this study was to evaluate the effects of adding ketamine to standard emergency department (ED) therapy for patients with status asthmaticus. This was a prospective observational study. Ten patients with an acute exacerbation of asthma who were unresponsive to standard therapy were enrolled in the ED. Upon enrollment, children received ketamine at a loading dose of 1 mg/kg intravenously (i.v.), followed by a continuous infusion of 0.75 mg/kg/hr (12.5 microg/kg/min) for 1 hr. Clinical asthma score (CAS), vital signs, and peak expiratory flow (PEF) measurements were obtained prior to ketamine administration, within 10 min after ketamine administration was completed, and 1 hr after infusion. Median CAS on ED arrival was 15 (range 7-23) and did not significantly change immediately prior to infusion of ketamine (median 14, range 8-21). Median CAS decreased to 10.5 immediately after infusion and to 9.51 hr post ketamine infusion (37% reduction, p < 0.05 by ANOVA vs. preketamine CAS). Median respiratory rate (RR) also decreased from 39 prior to ketamine to 30 immediately following ketamine administration (25% decrease vs. preketamine; p < 0.05). Oxygen saturation significantly improved after ketamine infusion, although 5 patients remained on oxygen. Median PEF improved after infusion, but was not statistically significant. Four patients experienced mild side effects including mild hallucinations, diffuse flushing, and moderate hypertension. Side effects resolved with benzodiazepines or with discontinuation of the infusion. Addition of ketamine to standard therapy was associated with improved indices of acute asthma severity. Side effects were transitory and comparable to previous studies. However, a double-blinded randomized controlled trial needs to be conducted to determine if improvement is attributable to the addition of ketamine to standard asthma therapy. PMID- 11758895 TI - Serum levels of interleukins (IL)-4, IL-5, IL-13, and interferon-gamma in acute asthma. AB - T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-y would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN gamma were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-gamma with initial forced expiratory volume in 1 sec (FEV1). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL 5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-gamma (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV1 and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV1 was associated with higher IL-5 and/or lower IFN gamma levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-gamma are associated with severe airway obstruction. PMID- 11758896 TI - Efficacy of inhaled budesonide and oral theophylline in asthmatic subjects. AB - The aim of present study was to evaluate clinical, functional, and anti inflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10 day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 microg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in I sec (FEV1) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV1 values (p < 0.05). These changes were more significant in group I than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline. PMID- 11758898 TI - Perception of bronchoconstriction in elderly asthmatics. AB - The impaired perception of bronchoconstriction in asthmatic patients may increase the risk of severe exacerbation. To characterize the perception of bronchoconstriction in elderly asthma patients, we compared the perception in older patients with that of younger patients. To determine the influence of perception of long-standing diseases, we further evaluated the perception in early-onset elderly asthma patients and in late-onset elderly asthma patients. The study group consisted of 80 stable asthmatic patients. The patients were grouped according to their age (group 1, < 60 years, n = 37, group 2, > or = 60 years, n = 43). Each group was separated into two subgroups according to the duration of symptoms (late-onset asthma 1A and 2A, < 5 years, early-onset asthma 1B and 2B, > or = 5 years). A histamine inhalation test was performed for each patient. Dyspnea was assessed by modified Borg scale. The Borg score in forced expiratory volume in 1 sec (FEV1) reduction by 20% was determined as perception score 20 (PS20). The mean perception scores of the elderly asthmatic patients were significantly lower than those of the younger asthmatic patients (group 1, PS20 = 2.35 +/- 0.17; group 2, PS20 = 1.37 +/- 0.12, p < 0.0001). The differences of mean perception score (PS20) between early- and late-onset subgroups were insignificant (IA, 2.63 +/- 0.30 and IB, 2.07 +/- 0.16, p = 0.101; 2A, 1.36 +/- 0.19 and 2B, 1.59 +/- 0.120, p = 0.91). The mean perception scores of male asthmatic patients were significantly lower than those of female patients (p = 0.03). There was a correlation between PS20 and % FEV1 in the younger group (r = 0.392, p = 0.02), but not in the elderly group (r = 139, p = 0.375). The correlation between PS20 and PD20 in both younger and elderly group was insignificant (p > 0.05). Elderly asthmatics perceive less intense respiratory distress for a decrease of 20% in FEV1 than do younger asthmatics. This underperception of bronchoconstriction may result in a delay in medical care during an acute asthmatic episode. Thus, we strongly recommend that elderly asthmatic patients should be followed up more frequently and closely. PMID- 11758897 TI - Improving pediatric asthma patient outcomes by incorporation of effective interventions. AB - Asthma affects approximately 5 million children in the United States. This disease results in billions of dollars of expenditures for hospitalizations, emergency admissions, medications, equipment, and indirect costs such as lost work productivity. This article describes how children with asthma received in depth evaluations and education, long-term control medications, and Air Watch monitoring to improve treatment adherence, asthma control, and asthma severity. Study patients (n = 99) received patient care and education according to the protocols of the Pediatric Asthma Clinic, Lovelace Health Systems (Albuquerque, NM). All enrolled patients were prescribed fluticasone propionate and salmeterol xinafoate based on asthma severity and the National Institutes of Health guidelines. In addition, each patient used the AirWatch electronic airway monitoring system. Patients (n = 80) who participated in the study for 6 months demonstrated overall improved adherence to prescribed medications and better control of asthma. Adherence to the AirWatch system decreased over time, most likely due to improvements in the way the patients felt. In conclusion, treatment adherence, asthma control, and asthma severity can be improved with comprehensive patient education, long-term control medications, and objective home pulmonary function monitoring. PMID- 11758899 TI - Structure of green pigment formed by the reaction of caffeic acid esters (or chlorogenic acid) with a primary amino compound. AB - A marked greening observed in some foods such as sweet potato, burdock, and others during food processing was shown to be due to green pigment formation by the condensation reaction of two molecules of chlorogenic acid or caffeic acid ester with one molecule of a primary amino compound under aeration in alkaline solution. Reduction of the green pigment by ascorbic acid or NaBH4 gave a yellow product, which readily turn green and then blue in air. The reduced and acetylated product of the green pigment was identified to be a novel trihydroxy benzacridine derivative, and the yellowish ethanol solution of this product immediately turned green upon addition of butyl amine or diluted alkali. Therefore, the green pigment was assumed to be an oxidized quinone type product of trihydroxy benzacridine. This identification of the structure was supported by the correspondence of the measured absorption spectra with those calculated by the molecular orbital method. A possible charge transfer complex between products of different oxidation steps in green solution was proposed. PMID- 11758900 TI - Development of free radical products during the greening reaction of caffeic acid esters (or chlorogenic acid) and a primary amino compound. AB - ESR spectra were measured directly on a marked greening reaction mixture of Et caffeate and a primary amino compound in alkali solution under aeration. A clear hyperfine structure was commonly detected early in the greening reaction with different amino compounds. Its hyperfine spectrum split into seven peaks was analyzed and found to be due to the oxidized free radical product of the Et caffeate using an authentic sample system. Another type of hyperfine ESR spectrum was observed later in the reaction, and was altered with different amino compounds. The hyperfine structure for n-butylamine split into 12 lines. The latter type of free radical products were assumed to be a semiquinone type radical compound of the trihydroxy benzacridine derivative, which was identified as the principal structure of the green and yellow pigments formed by this greening reaction system. A formation mechanism of the green pigment and related products involving these free radical products is proposed. PMID- 11758901 TI - Effects of rooibos tea extract on antigen-specific antibody production and cytokine generation in vitro and in vivo. AB - Rooibos tea contains a large amount of flavonoids and acts as a potent antioxidant. In this study, we examined the effects of Rooibos tea extract on antigen-specific antibody production and cytokine generation in vitro and in vivo. The primary in vitro anti-ovalbumin (anti-OVA) or sheep red blood cell (SRBC) antibody production in murine splenocytes was markedly stimulated by the addition of the tea extract at concentrations of 1-100 microg/ml. On the other hand, a nonspecific antibody response elicited with lipopolysaccharide (LPS) in purified splenic B-cells was not modified by the extract. Rooibos tea extract caused an increase in the generation of interleukin 2 (IL-2) both in OVA- and anti-CD3-primed splenocytes at concentrations ranging from 10 microg/ml to 1000 microg/ml. In contrast, this tea extract suppressed the generation of interleukin 4 (IL-4) in OVA-primed splenocytes. Moreover, the reduction of OVA-induced antibody production in serum of the cyclosporin A (CyA) -treated rats can be significantly restored and the IL-2 generation in murine splenocytes was stimulated, following oral administrations of Rooibos tea extract. Thus, our findings suggested that Rooibos tea extract may facilitate the antigen-specific antibody production through selective augmentation of IL-2 generation both in vitro and in vivo. Collectively, Rooibos tea intake may be of value in prophylaxis of the diseases involving a severe defect in Th1 immune response such as cancer, allergy, AIDS, and other infections. PMID- 11758902 TI - Regulation by two CatR proteins that differ in binding affinity to catB promoters expressing two cat gene clusters. AB - We isolated the two LysR-type regulatory proteins CatR1 and CatR2, which regulate the expression of cat1 and cat2 gene clusters, respectively, required for catechol degradation in the bacterium Frateuria sp. ANA-18. In a gel mobility shift assay using CatR1 and the DNA fragment containing the catB1 promoter region, the formation of two complexes, complex 1-1 (C1-1) and complex 1-2 (C1 2), was observed in the presence of cis,cis-muconate. On the other hand, CatR2 and the DNA fragment containing the catB2 promoter region formed only complex 2-2 (C2-2) at a lower concentration of cis,cis-muconate than that at which C1-1 and C1-2 were formed. As the concentration of cis,cis-muconate decreased, the production of the muconate cycloisomerase isozyme MC II encoded by catB2 decreased as well as that of MC I encoded by catB1. However, the amount of MC II synthesized was larger than that of MC I at low concentrations. On the basis of these results, we concluded that the catB2 promoter was activated at low concentrations of cis,cis-muconate. PMID- 11758903 TI - Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats. AB - To discover the role of the kidney in tryptophan degradation, especially tryptophan to niacin, rat kidneys were injured by feeding a diet containing a large amount of adenine. The kidney contains very high activity of aminocarboxymuconate-semialdehyde decarboxylase (ACMSD), which leads tryptophan into the glutaric acid pathway and then the TCA cycle, but not to the niacin pathway. On the other hand, kidneys contain significant activity of quinolinate phosphoribosyltransferase (QPRT), which leads tryptophan into the niacin pathway. The ACMSD activity in kidneys were significantly lower in the adenine group than in the control group, while the QPRT activity was almost the same, however, the formations of niacin and its compounds such as N1-methylnicotinamide and its pyridones did not increase, and therefore, the conversion ratio of tryptophan to niacin was lower in the adenine group than in the control group. The contents of NAD and NADP in liver, kidney, and blood were also lower in the adenine group. The decreased levels of niacin and the related compounds were consistent with the changes in the enzyme activities involved in the tryptophan-niacin metabolism in liver. It was concluded from these results that the conversion of tryptophan to niacin is due to only the liver enzymes and that the role of the kidney would be extremely low. PMID- 11758904 TI - Superoxide- and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities of soyasaponin beta g related to gallic acid. AB - Soyasaponin beta p g at 1 mm had 8% scavenging activity for O2-, and 25 microM beta g scavenged 20.9% for the DPPH radical (IC50: 63.8 microM). In the soyasaponin beta g-gallic acid system, synerigistic effects were observed at a low level of gallic acid concentration. The spin density distribution calculated by the MNDO/AM1 method showed unpaired electron localization on the carbons at C 4 and C-6, and on the ketone group at C-4 of the DDMP moiety. Furthermore, for soyasaponin beta g, the MNDO/AM1 method gave an ionization potential of 8.38 eV, electron affinity of 1.16 eV and Mulliken electronegativity of 4.77 eV. Based on this evidence, the synergistic antiradical effects of the soyasaponin beta g gallic acid system are assumed to involve two-electron reduction from gallic acid. PMID- 11758905 TI - Orotic acid added to casein, but not to egg protein, soy protein, or wheat gluten diets increases 1,2-diacylglycerol levels and lowers superoxide dismutase activities in rat liver. AB - Effects of the dietary addition of orotic acid to a diet containing casein as a sole protein source on lipid levels in the liver and serum, activities of antioxidant enzymes in the liver, and some enzyme activities in serum, were compared with other diets containing egg protein, soy protein, or wheat gluten, respectively. 1. The contents in the liver of each lipid were increased by the addition of orotic acid as compared with those values without it. The orotic acid added to the casein diet caused accumulation of more liver total lipids, triacylglycerol, 1,2-diacylglycerol, and phospholipids than those fed three other diets. 2. The addition of orotic acid to the casein, but not to the other three diets, lowered the activities of liver superoxide dismutase and increased the activities of both serum ornithine carbamoyltransferase and alanine aminotransferase. Thus, the significant increase in serum ornithine carbamoyltransferase activities as the marker of liver lesions may result from the marked accumulation of liver lipids, decreased activities of hepatic superoxide dismutase, and the increased level of hepatic 1,2-diacylglycerol, followed by possibly the increased level of superoxide anion and increased activity of protein kinase C in rats fed the casein diet with orotic acid added. PMID- 11758906 TI - Phosphoglucose isomerase from bananas: partial characterization and relation to main changes in carbohydrate composition during ripening. AB - Some characteristics of phosphoglucose isomerase (PGI, EC 5.3.1.9) from banana were measured during fruit ripening of three banana cultivars. In banana, PGI was present as two dimeric isoenzymes, named PGI1 and PGI2, which had similar native molecular masses but differed in relation to heat stability and isoelectric point. Total PGI activity showed a distinct two-step change during fruit ripening. Before the climacteric period, PGI activity gradually decreased with the starch content, then its activity began to increase with sucrose accumulation. The ratio of PGI1, and PGI2 was constant, indicating that both enzymes would be involved in starch degradation and sucrose synthesis. PGI activity and changes in carbohydrate composition suggests the existence of some control to fit the requirements of the intense carbon flow from starch to sucrose. PMID- 11758907 TI - Supplemental silk protein, sericin, suppresses colon tumorigenesis in 1,2 dimethylhydrazine-treated mice by reducing oxidative stress and cell proliferation. AB - This study was done to discover the underlying mechanism of the inhibitory effect of sericin against colon tumorigenesis. Mice were fed a diet with 30 g/kg sericin for 115 d, and given a weekly injection of 1,2-dimethylhydrazine (10 mg/kg body weight) for the initial 10 wk. Dietary supplemental sericin caused a 62% reduction in the incidence of colonic adenoma (P<0.05), but did not affect the incidence of colonic adenocarcinoma. Sericin intake significantly reduced the number of colon adenomas. Consumption of sericin significantly reduced the BrdU labeling index of colonic proliferating cells and the expression of colonic c-myc and c-fos. The levels of colonic 8-hydroxydeoxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein were significantly suppressed by sericin. The results suggest that dietary sericin suppresses the development of colon tumors by reducing oxidative stress, cell proliferation, and nitric oxide production. PMID- 11758908 TI - Characterization of the cellulose-binding ability of Geotrichum sp. M111 cells and its application to dehydration of the distilled waste of sweet potato shouchu. AB - The cellulose-binding ability of Geotrichum sp. M111 cells was investigated by the micro-tube method which gives an indication of the binding ability of M111 cells. The optimum pH value and temperature were 3-7 and below 50 degrees C, respectively, from measurement of the aggregation height for a mixture of cellulose powder and M111 cells. The binding constant of 0.3% for M111 cells to cellulose powder was obtained in a 20 mm citrate buffer of pH 5.0 at 30 degrees C. Aggregation was inhibited by such surfactants as sodium dodecylsulfate. The binding ability of M111 cells to cellulose fiber disappeared after a treatment with Driselase or Pronase E. This suggests that the binding ability might be related to the cell surface proteins. The dehydration rate of the distilled waste of sweet potato shouchu was accelerated by the addition of M111 cells. The analysis of dehydration by a linear viscoelastic model suggests that the acceleration effect might have been due to the space increase between cellulose fibers with the cell addition. PMID- 11758909 TI - Chemistry of zerumbone. 2. Regulation of ring bond cleavage and unique antibacterial activities of zerumbone derivatives. AB - Further investigation of the chemistry of the eleven-membered cyclic sesquiterpene, zerumbone, the major component of the wild ginger, Zingiber zerumbet Smith, has revealed a new selective epoxidation process, a further example of a novel Favorskii-initiated double ring contraction, and a regiospecific fragmentation of zerumbone dibromide derivatives. Several zerumbone derivatives were found to be selective inhibitors of the growth of gram-positive bacteria. PMID- 11758910 TI - Increased energy metabolism and suppressed body fat accumulation in mice by a low concentration of conjugated linoleic acid. AB - We investigated the dose-effect of the long-term intake of conjugated linoleic acid (CLA) on the energy metabolism and fat accumulation in mice. Five-week-old male Std ddY mice were fed on a diet containing none (control), 0.25%, 0.5% or 1.0% CLA for 4 or 8 weeks. The body weight was lower in the CLA groups than in the control group, and significant differences were detected between the 1.0% CLA group and the control group at both 4 and 8 weeks. The epididymal and perirenal adipose tissue weights were significantly lower in the CLA groups than in the control group. The liver weight and hepatic triglyceride values were higher in the 1.0% CLA group than in the other groups. The metabolic rate was measured after 8 weeks by using a gas analyzer. The oxygen consumption of the mice in the CLA groups was significantly higher than that of the control mice. Since there was a significant effect on the mice supplemented with 0.25% CLA, low concentration of CLA is suggested to suppress the body fat accumulation and increase the energy metabolism. PMID- 11758911 TI - Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells. AB - Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 microM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 microM DADS and 10-100 microM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 microM of DADS and 10-100 microM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P. PMID- 11758912 TI - Purification and characterization of a O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine from Vitis vinifera L. (cv. Cabernet Sauvignon). AB - An S-adenosyl-L-methionine-dependent O-methyltransferase capable of methylating 2 hydroxy-3-alkylpyrazine (HP) was purified 7,300-fold to apparent homogeneity with an 8.2% overall recovery from Vitis vinifera L. (cv. Cabernet Sauvignon) through a purification procedure including column chromatography on DEAE-Sepharose FF, Ether-5PW, hydroxyapatite, G2000SW(XL), and DEAE-5PW. The relative molecular mass of the native enzyme estimated on gel permeation chromatography was 85 kDa, and the subunit molecular mass was estimated to be 41 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme also methylates caffeic acid. The Vmax for IBHP and caffeic acid were 0.73 and 175 pkatals/mg, respectively, and the respective Km for IBHP and caffeic acid were 0.30 and 0.032 mm. The optimum pH for IBHP (8.5) was different from that for caffeic acid (7.5). PMID- 11758913 TI - Transfer of soy isoflavone into the egg yolk of chickens. AB - A diet containing a high concentration of soy isoflavone was administered to laying hens and the contents of the isoflavones transferred to the plasma and egg yolk were measured. A method for quantitatively measuring the concentration of isoflavone in the yolk was first established, before a high concentration of soy isoflavone was administered to the laying hens over an 18-day period. The concentrations of isoflavone in the plasma and egg yolk reached their highest on the 12th day of the feeding period, the values being 3,167 nmol/l and 65.29 microg/100 g, respectively. The concentration of cholesterol in the yolk was slightly affected during the early stages of the feeding period. These findings clearly demonstrate that soy isoflavone was transferred into the yolk from the feed and that the cholesterol concentration in the yolk was affected by administering the soy isoflavone-enriched feed. PMID- 11758915 TI - Catalytic function of the residues of phenylalanine and tyrosine conserved in squalene-hopene cyclases. AB - Site-directed mutagenesis experiments on all the conserved residues of Phe and Tyr in all the known squalene-hopene cyclases (SHCs) were carried out to identify the active site residues of thermophilic Alicyclobacillus acidocaldarius SHC. The following functions are proposed on the basis of kinetic data and trapping of the prematurely cyclized products: (1) The Y495 residue probably amplifies the D376 acidity, which is assumed to work as a proton donor for initiating the polycyclization cascade, but its role is moderate. (2) Y609 possibly assists the function of F365, which has previously been assigned to exclusively stabilize the C-8 carbocation intermediate through cation-pi interaction. The Y609A mutant produced a partially cyclized bicyclic triterpene. (3) Y612 works to stabilize both the C10 and C8 carbocations, this being verified by the finding that mono- and bicyclic products were formed with the Y612A mutant. (4) F129 was first identified to play a crucial role in catalysis. (5) The three residues, Y372, Y474 and Y540, are responsible for reinforcing the protein structure against thermal denaturation, Y474 being located inside QW motif 3. PMID- 11758914 TI - A novel membrane protein complex on the endoplasmic reticulum and early Golgi compartments in the yeast Saccharomyces cerevisiae. AB - A novel membrane protein, Yml067c in the systematic ORF name, was discovered as a component of immunoisolated vesicles of the early Golgi compartment of the yeast Saccharomyces cerevisiae (Cho et al., FEBS Lett. 469, 151-154 (2000)). Conserved sequences having sequence similarity to Yml067c were widely distributed in the eukaryotes and one of them, Yal042w, was found in the Saccharomyces genome database. In the yeast cell, Yml067c and Yal042w were found to form a heterooligomeric complex by immunoprecipitation of their tagged derivatives from the detergent-solubilized membrane. Cell fractionation and indirect immunofluorescent staining indicated that the majority of these proteins were localized on the ER membrane. Therefore, the Yml067c-Yal042w complex should shuttle between the ER and the early Golgi compartment as well as the p24-family proteins. PMID- 11758916 TI - Cysteine proteinase gene expression in the endosperm of germinating carrot seeds. AB - A gene for carrot seed cysteine proteinase (CSCP; AB057371, AB057372) was cloned using PCR. The deduced amino acid sequence of CSCP had active sites for eukaryotic cysteine proteinases, putative signal sequences, and an endoplasmic reticulum targeting sequence. RNA gel blot analysis showed that CSCP transcripts appeared from dry seed, reached a maximum 3 days after imbibition (DAI), and disappeared by 5 DAI. In situ hybridization showed that CSCP transcripts accumulated in the endosperm of germinating seeds. This is the first report of the expression pattern of a cysteine proteinase gene in the endosperm of germinating dicotyledonous plants. The promoter of the CSCP gene had an endosperm motif and many other motifs also found in the promoters of endosperm-specific storage protein genes in monocotyledons. It is suggested that dicotyledons, like monocotyledons, have a temporal and spatial regulation system for endosperm specific gene expression in germinating seeds. PMID- 11758917 TI - Analysis of structural components and molecular construction of soybean soluble polysaccharides by stepwise enzymatic degradation. AB - Soybean soluble polysaccharides (SSPS) extracted from soybean cotyledons have a pectin-like structure. The core polysaccharides after treatments with four kinds of hemicellulases and a pectinase contained approximately equal numbers of L rhamnose and D-galacturonate residues, suggesting the presence of the rhamnogalacturonan (RG) I structure consisting of the diglycosyl repeating unit, 4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-. The lengths of RG chains were calculated as approximately 15, 28, and 100 diglycosyl repeats. The RG components linked to each other by intervention of galacturonan (GN) chains, constituting the backbone of SSPS. All arabinose residues, which constitute 21% of total SSPS sugars, were found to be in side chains from RG regions, and this was also true for galactose residues, which constitute 50% of total sugars. Of arabinose residues, 94% are present as alpha-1,3- or alpha-1,5-arabinans, and 89% of galactose residues were present as beta-1,4-galactans. Galactan chains are modified with arabinose, xylose, fucose, and glucose at the sites close to the RG regions. PMID- 11758918 TI - Protein engineering of novel proteinase inhibitors and their effects on the growth of Spodoptera exigua larvae. AB - Novel types of proteinase inhibitors with multi-inhibitory activities were generated by replacement of phytocystatin domains in sunflower multi-cystatin (SMC) by the serine proteinase inhibitor BGIT from bitter gourd seeds. Two chimeric inhibitors SMC-T3 and SMC-T23, in which the third domain in SMC and the second and third domains in SMC were replaced by BGIT, acquired trypsin inhibitory activity (Ki: 1.46 x 10(-7) M and 1.75 x 10(-7) M), retaining inhibitory activity toward papain (Ki: 4.5 x 10(-8) M and 1.52 x 10(-7) M), respectively. We compared the chimeric inhibitors and the recombinant SMC (r-SMC) in relation to their effects on the growth of larval Spodoptera exigua. When the second instar larvae were reared on a diet containing rSMC, SMC-T3, or SMC-T23 for ten days, a significant reduction in weight gain was observed. Mean weights for rSMC, SMC-T3, and SMC-T23 were 43 mg, 32 mg, and 43 mg, respectively, as compared with that (60 mg) for the absence of the inhibitor. In contrast, BGIT had little effect on the growth of the S. exigua larvae. This result indicated that the chimeric inhibitor SMC-T3 with two phytocystatin domains and one serine proteinase inhibitor domain is an efficient inhibitor of proteinases in the S. exigua larvae. Therefore, this novel type of proteinase inhibitor with multi inhibitory activities may represent a promising protein for successful application to a transgenic plant with insect resistance. PMID- 11758919 TI - Glycolic acid production using ethylene glycol-oxidizing microorganisms. AB - Screening for microorganisms oxidizing ethylene glycol to glycolic acid was carried out. Among stock cultures, several yeasts and acetic acid bacteria showed high glycolic acid producing activity. Pichia naganishii AKU 4267 formed the highest concentration of glycolic acid, 35.3 g/l, from 10% (v/v) ethylene glycol (molar conversion yield, 26.0%). Among soil isolates, Rhodotorula sp. 3Pr-126, isolated using propylene glycol as a sole carbon source, formed the highest concentration of glycolic acid, 25.1 g/l, from 10% (v/v) ethylene glycol (molar conversion yield, 18.5%). Rhodotorula sp. 3Pr-126 showed higher activity toward 20% (v/v) ethylene glycol than P. naganishii AKU 4267. Optimization of the conditions for glycolic acid production was investigated using P. naganishii AKU 4267 and Rhodotorula sp. 3Pr-126. Under the optimized conditions, P. naganishii AKU 4267 and Rhodotorula sp. 3Pr-126 formed 105 and 110 g/l of glycolic acid (corrected molar conversion yields, 88.0 and 92.2%) during 120 h of reaction, respectively. PMID- 11758920 TI - Sorbicillinol, a key intermediate of bisorbicillinoid biosynthesis in Trichoderma sp. USF-2690. AB - In the course of our screening program for free radical scavengers from Trichoderma sp. USF-2690, we found an unidentified metabolite (1) that appeared by the method used for HPLC analysis. Metabolite 1 gradually decreased with the production of bisorbicillinoids and was easily missed during the general isolation procedure. The LC-ESI-MS (negative) analysis for 1 gave m/z 247 as the (M-1)- ion peak. The hydrolysis of synthetic 6-O-acetylsorbicillinol (+/- -2) by 0.05 M KOH and acetylation of product 1 in an aqueous solution indicated that the structure of 1 was (6S)-4-(2,4-hexadienoyl)-3,6-dihydroxy-2,6-dimethyl-2,4 cyclohexadien-1-one, designated sorbicillinol, a quinol that has been postulated to be important in bisorbicillinoid biosynthesis. PMID- 11758921 TI - Molecular characterization of beta-tubulin gene from Pleurotus sajor-caju. AB - A beta-tubulin gene (TUB1) from the basidiomycete Pleurotus sajor-caju was sequenced. TUB1 encodes a 446-amino-acid protein. The coding region is interrupted by 9 introns, all of which had a 5'-GTRNGT... YAG-3' sequence at the boundaries. Locations of the introns in TUB1 were common between the beta-tubulin genes of other basidiomycetes, but not with animals, ascomycetes, or plants. This suggests that the introns were inserted independently into the beta-tubulin gene after these divisions had diverged. PMID- 11758922 TI - Effects of seasoning and heating device on mutagenicity and heterocyclic amines in cooked beef. AB - Pan-roasted beef showed a lower mutagenicity after various degrees of cooking than charcoaled one. The high mutagenicity of charcoaled beef was due to the formation of more heterocyclic amines, especially AalphaC (2-amino-9H-pyrido- [2,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) because of rapid and direct heating on the surface of the meat at a high temperature. Seasoning decreased mutagenicity of pan-roasted beef except the very well done sample with unchanged heterocyclic amine contents, but increased mutagenicity of charcoaled beef with decreased levels of AalphaC and PhIP, probably due to the change of heterocyclic amine precursors or alternatively to the occurrence of other mutagens. PMID- 11758923 TI - Dehydroascorbic acid reduction in several tissues and cultured hepatocytes of the chicken. AB - Dehydroascorbic acid, the oxidized form of ascorbic acid, is rapidly reduced to ascorbate in living organs (ascorbate recycling). We examined the GSH-dependent dehydroascorbate reductase activity in several tissues of the chicken. The activity was highest in the liver, and second highest in the brain. The activity was localized in the cytosol fraction of the liver. We subsequently examined the dehydroascorbate reduction in separated chicken hepatocytes. The cellular ascorbate concentration was elevated in dehydroascorbate-treated cells. It is thought that hepatocytes incorporated external dehydroascorbate and converted it into ascorbate. These findings suggest that the liver plays an important role in ascorbate recycling by the chicken. PMID- 11758924 TI - Comparison of three signals for secretory expression of recombinant human midkine in Pichia pastoris. AB - The secretion signals of Saccharomyces cerevisiae alpha mating factor, human midkine itself, and Pichia pastoris acid phosphatase, were tried for the expression of human midkine under the control of the AOX1 gene promoter in P. pastoris. Approximately 28 mg/l, 1.5 mg/l, and 0.2 mg/l of midkine were secreted by using the a mating factor pre-pro-sequence, the midkine signal sequence, and the phosphatase signal sequence in flask cultures, respectively. PMID- 11758925 TI - Anti-stress and anti-fatigue effects of fermented rice bran. AB - The anti-stress and anti-fatigue effects on rats and mice of a hot water extract of rice bran fermented with Saccharomyces cerevisae IFO 2346 were investigated. Oral administration (1 g/kg/day) of the hot water extract of fermented rice bran (FRB) inhibited major changes in the weight of the adrenal, thymus, spleen and thyroid, showing an anti-stress effect. The hot water extract of FRB also inhibited increases in the GPT and LDH activity, cholesterol and glucose in the serum. The administration (1 g/kg/day) for 2 weeks significantly prolonged the swimming time, resulting in an increase in the anti-fatigue effect. It is considered from these results that FRB had anti-stress and anti-fatigue effects. PMID- 11758926 TI - The long terminal repeat (LTR) sequence of marY1, a retroelement from the ectomycorrhizal homobasidiomycete Tricholoma matsutake, is highly conserved in various higher fungi. AB - marY1 is an LTR-retroelement from the homobasidiomycete Tricholoma matsutake. Nucleotide sequences that correspond to the putative U3-R region and the R-U5 region of marY1 are highly conserved in various higher fungi. Data suggest that the LTR sequence of marY1 originated early in the evolution of higher fungi and has become widely distributed. Therefore, it may be useful for the construction of an LTR-mediated transformation system in basidiomycetes. PMID- 11758927 TI - marY2N, a LINE-like non-long terminal repeat (non-LTR) retroelement from the ectomycorrhizal homobasidiomycete Tricholoma matsutake. AB - A LINE-like non-LTR retroelement designated marY2N was cloned from the ectomycorrhizal homobasidiomycete Tricholoma matsutake. marY2N has open reading frames that correspond to gag and pol, and a putative promoter and consensus sequences common to those of the mutators from fruit flies. While it is common to T. matsutake and Tricholoma magnivelare, marY2N does not reside in any other species of Tricholoma tested. PMID- 11758929 TI - Isolation and identification of antheridiogens in the ferns, Lygodium microphyllum and Lygodium reticulatum. AB - Antheridiogens in culture media of 6-week-old prothallia of two species of Schizaeaceous ferns, Lygodium microphyllum and Lygodium reticulatum, were analyzed by gas chromatography-mass spectrometry. In both species, the gibberellin A73 methyl ester (GA73-Me) was identified as the most abundant antheridiogen, and the methyl esters of GA9 and of several monohydroxy-GA73 derivatives were also detected. Since both species produced antheridiogens at a high level, they were classified into high-antheridiogen-producing ferns. The response to GA73-Me of gametophytes of both species is also discussed. PMID- 11758928 TI - Antibacterial agents that inhibit histidine protein kinase YycG of Bacillus subtilis. AB - We demonstrated in vitro that YycG-YycF of Bacillus subtilis constitutes a two component system and shows a specificity of the sensor protein for the cognate phosphorylation partner. Based on inhibition of such an autophosphorylation of YycG, we searched imidazole and zerumbone derivatives to identify the antibacterial agents such as NH125, NH126, NH127, and NH0891. PMID- 11758930 TI - Structural elucidation and synthesis of 3-hydroxybenzene-1,2-dicarbaldehyde from astigmatid mites. AB - The structure of a novel aromatic compound contained in the unidentified Rhizoglyhus mite (Acaridae: Astigmata) was elucidated, without its isolation, to be 3-hydroxybenzene-1,2-dicarbaldehyde (tentatively named gamma-acaridial) by a combination of GC/MS and GC/FT-IR together with knowledge of related mite compounds. The structure was confirmed by a 5-step synthesis, starting from methyl 3-hydroxybenzoate, in a 15% overall yield. The compound is widely distributed not only among Astigmata but also among Oribatida, although its biological function is obscure at present. PMID- 11758931 TI - Hypoglycemic effect of a hot-water extract from defatted sesame (Sesamum indicum L.) seed on the blood glucose level in genetically diabetic KK-Ay mice. AB - Genetically diabetic (type II) KK-Ay mice, male and 5 weeks of age, were divided into one group of 12 mice that were fed on a basal (BAS) diet and three groups of 6 mice each that were fed on the test diets for 4 weeks. Each test diet contained 4.0% of the hot-water extract (HES) from defatted sesame (Sesamum indicum L.) seed, 1.4% of the water eluent fraction (WFH) of HES or 0.7% of the methanol eluent fraction (MFH) of HES from a glass column packed with HP-20 resin. At the end of the feeding period, the BAS group was divided into the MAL and MALH groups which were respectively force-fed with 1 ml per mouse of a 20% maltose solution in water with or without 4.0% HES. The plasma glucose concentration and amount of urinary excreted glucose were lower from the HES and MFH diets than from the BAS and WFH diets. The levels of plasma glucose and serum insulin were lower in the MALH group than in the MAL group. These results indicate that HES and MFH had a reductive effect on the plasma glucose concentration of KK-Ay mice, and this effect is suggested to have been caused by the delayed glucose absorption. PMID- 11758932 TI - Chemical synthesis and biological activity of the gelatinase biosynthesis activating pheromone of Enterococcus faecalis and its analogs. AB - An 11-residue peptide lactone, termed the gelatinase biosynthesis-activating pheromone (GBAP), triggers the production of the pathogenicity-related extracellular proteases, gelatinase and serine protease, in Enterococcus faecalis. In this study, we synthesized GBAP and its analogs and examined their gelatinase biosynthesis-inducing activity. This study on the structure-activity relationship shows that a lactone ring was indispensable for the activity. PMID- 11758933 TI - Lactobacillus casei NY1301 increases the adhesion of Lactobacillus gasseri NY0509 to human intestinal caco-2 cells. AB - In the presence of Lactobacillus casei NY1301, the adhesion of Lactobacillus gasseri NY0509 to cultured human intestinal Caco-2 cells was significantly increased (P<0.01). In contrast, L. gasseri NY0509 did not affect the adhesion of L. casei NY1301. A heat-stable cell component of L. casei NY1301 was involved in this increase of adhesion. These results suggest that a combination of these strains may have synergistic effects of adhesion to human intestinal mucosa. PMID- 11758934 TI - Isolation and some characterization of an acidic polysaccharide with anti calcification activity from coccoliths of a marine alga, Pleurochrysis carterae. AB - Coccolith is a calcified scale with species-specific fine structure produced by marine unicellular coccolithophorid algae, and consists of calcium carbonate crystals and organic matrices. EDTA-soluble organic materials extracted from coccoliths of Pleurochrysis carterae showed anti-calcification activity. They were separated by anion-exchange HPLC, and two fractions, fractions A and B, were obtained. Fraction B, which was more active than fraction A, was further separated into six consecutive fractions, B1-B6, by second anion-exchange HPLC. 1H NMR spectral analyses of these fractions suggested that a novel acidic polysaccharide, designated CMAP, existed throughout B1-B6 and that the latter four fractions mainly contained another acidic polysaccharide, PS-2, characterized previously. Since PS-2 did not show anti-calcification activity, CMAP was found to be the active principle. PMID- 11758935 TI - Screening for phenoloxidases from edible mushrooms. AB - A screening test for phenoloxidases from edible mushrooms was done on potato dextrose agar plates that contained phenolic chemicals. Many edible mushrooms showed positive reactions on the agar plates. Among them, Auricularia auricula judae, Clitocybe nebularis, Lentinus edodes, Pholiota aurivella, and Pseudohiatula oshimae produced a considerable amount of phenoloxidases, and these enzymes showed maximum activities in the acidic pH region. PMID- 11758936 TI - Apoptosis induced by picolinic acid-related compounds in HL-60 cells. AB - We have found that niacin-related compounds, particularly picolinic acid, induced apoptosis in human leukemia cells. In this paper, we investigated whether various picolinic acid-related compounds had apoptosis-inducing activities or not. Particularly, fusaric acid, picolinaldehyde, nicotinaldehyde, 2-aminopyridine, and 3-aminopyridine also induced apoptosis in HL-60 cells. These results suggest that pyridine substituted with various groups and the consequent change of resonance structure may have an important role in the induction of apoptosis. PMID- 11758937 TI - No factors except for the hap complex increase the Taka-amylase A gene expression by binding to the CCAAT sequence in the promoter region. AB - To examine the possibility that factors different from the Hap complex are involved in increasing Taka-amylase A gene (taa) expression in Aspergillus nidulans, either the authentic taa gene or the mutant taa gene with a replacement of the CCAAT box was expressed in either a wild type strain or a mutant strain lacking the functional Hap complex (hapCdelta). When the mutant taa was expressed in the hapCdelta strain, enzyme activity was as low as that of the hapCdelta strain transformed with the authentic taa gene, indicating that no factors except for the Hap complex increase transcription of the taa gene by binding to the CCAAT sequence. PMID- 11758938 TI - Characterization of nucleoside diphosphate kinase from moderately halophilic eubacteria. AB - Nucleoside diphosphate kinase was purified to apparent homogeneity from naturally isolated moderately halophilic eubacteria by ATP-agarose and phenyl-5PW column chromatographies. The molecular mass of this enzyme was 15 kDa by time-of-flight mass-spectrometry. This protein showed anomalous mobility on SDS-PAGE which is typical of a halophilic protein. It was stable and active over a wide range of salt concentrations, from 0 to 4.0 M NaCl. PMID- 11758939 TI - Genetic analysis of the His-to-Asp phosphorelay implicated in mitotic cell cycle control: involvement of histidine-kinase genes of Schizosaccharomyces pombe. AB - Common histidine-to-aspartate (His-to-Asp) phosphorelay signaling systems involve three types of signaling components: a sensor His-kinase, a response regulator, and a histidine-containing phosphotransfer (HPt) protein. In the fission yeast Schizosaccharomyces pombe, two response regulators, Mcs4 and Prr1, have been identified, and it was shown that they are involved in signal transduction in stress responses. Furthermore, Mcs4 and Prr1 appear to be involved in mitotic cell-cycle control and meiosis, respectively. Recently we have identified Spy1 (also known as Mpr1), which encodes an HPt phosphotransmitter, and reported that Spy1, together with Mcs4, plays a role in cell cycle regulation. In this study, we identified and characterized three genes encoding histidine kinase, named Phk1, Phk2, and Phk3 (S. pombe histidine kinase) (also referred as Mak2, Mak3, and Mak1, respectively). Deletion of individual kinase genes has no apparent phenotypes but multiple deletion of these kinases showed the same phenotype of Spyl (Mpr1)-deficient cells, indicating precocious entry into M phase. These results indicated that three histidine kinases that work upstream of the HPt transmitter, Spy1 (Mpr1), have a redundant function in cell cycle control. PMID- 11758940 TI - Purification and some properties of an inhibitor for a yeast pleiotropic drug resistant pump from Kitasatospora sp. E-420. AB - A strain producing an inhibitor for pleiotropic drug resistant 5 (Pdr5) was isolated using our original screening system in yeast. The strain was classified and named as Kitasatospora sp. E-420. The purified inhibitor (molecular weight = 1,193 by FAB-MS) inhibited a Pdr5-mediated efflux of cycloheximide and cerulenin. The intracellular accumulation of a fluorescent dye, rhodamine 123, by the inhibitor was also confirmed. Some physicochemical data suggested that the Pdr5 specific inhibitor was different from an immunosuppressant, FK506, reported as the only inhibitor of Pdr5 in vivo. PMID- 11758941 TI - Antimutagenic activity against trp-P-1 of the edible Thai plant, Oroxylum indicum vent. AB - A methanolic extract of Oroxylum indicum strongly inhibited the mutagenicity of Trp-P-1 in an Ames test. The major antimutagenic constituent was identified as baicalein with an IC50 value of 2.78+/-0.15 microM. The potent antimutagenicity of the extract was correlated with the high content (3.95+/-0.43%, dry weight) of baicalein. Baicalein acted as a desmutagen since it inhibited the N-hydroxylation of Trp-P-2. PMID- 11758942 TI - Appearance of poor-fermenting variants in brewing yeast culture. AB - A class of yeast variants appears after cultivation of a bottom-fermenting brewing yeast strain, IFO2003. Although IFO2003 fails to grow well above 33 degrees C, the variants can grow up to 34 degrees C. Temperature-resistance and an acquired phenotype of maltose poor-fermentation ability are strictly correlated in the bottom-fermenting brewing yeast, enabling us to develop easy estimation of the fermentation ability of the variants. PMID- 11758943 TI - Characterization of the RcsC-->YojN-->RcsB phosphorelay signaling pathway involved in capsular synthesis in Escherichia coli. AB - Escherichia coli and other enteric microorganisms produce an extracellular polysaccharide capsule, called colanic acid, under certain environmental conditions. This capsular synthesis is regulated by the RcsC (sensor kinase)- >YojN (phosphotransfer intermediate)-->RcsB (response regulator) phosphorelay signal transduction under certain growth conditions. Nonetheless, little is known about signals that exaggerate the Rcs-system. To gain insight into signals that activate the Rcs-system, here we searched for genes that activate the Rcs-system, provided that those on a multicopy plasmid were introduced into E. coli. We identified several such genes, namely, rcsB, rcsA, djlA, lolA, and ompG. The DjlA, LolA, and OmpG proteins are particularly interesting in that they are all located on the cell surface, where the primary sensor RcsC histidine-kinase is localized. Implications of these findings are discussed with special reference to the mechanism by which RcsC perceives external signals. PMID- 11758944 TI - Lipid metabolism in the heart--contribution of BMIPP to the diseased heart. AB - Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with this new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In other words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome proliferator-activated receptors (PPAR) just like a conductor of an orchestra. Most of the regulating mechanisms of the PPAR are still unknown, but reduction of this nuclear factor is shown in the process of decompensated heart failure. This review is based by mostly on our fundamental and Japanese clinical data. BMIPP has been used clinically in abundant cases in Japan. In such situations, further correct information on lipid metabolism, including BMIPP, will contribute to the understanding of deteriorating heart disease and its prognosis. PMID- 11758945 TI - Clinical value of lung uptake of iodine-123 metaiodobenzylguanidine (MIBG), a myocardial sympathetic nerve imaging agent, in patients with chronic heart failure. AB - This study investigated the clinical value of I-123 MIBG pulmonary accumulation and washout in patients with chronic heart failure (CHF). Nineteen patients with CHF and 15 normal volunteers (NL) were included. The uptake ratio of heart to mediastinum (H/M), that of lung fields to mediastinum (L/M), and washout rate (WR) of the heart and lung fields were calculated in anterior planar images and compared with results of echocardiography and cardiac catheterization. In the CHF group, the lung uptake in delayed images increased and lung WR was decreased, suggesting pulmonary endothelial lesions. Furthermore, there was a negative correlation between right and left lung WR and pulmonary arterial diastolic pressure (PA(D)) and pulmonary arterial systolic pressure (PA(s)) in the CHF group. Since the WR of MIBG reflected PA, it may be used as an index of severity of cardiac dysfunction. PMID- 11758946 TI - Comparison of parametric FBP and OS-EM reconstruction algorithm images for PET dynamic study. AB - An ordered subsets expectation maximization (OS-EM) algorithm is used for image reconstruction to suppress image noise and to make non-negative value images. We have applied OS-EM to a digital brain phantom and to human brain 18F-FDG PET kinetic studies to generate parametric images. A 45 min dynamic scan was performed starting injection of FDG with a 2D PET scanner. The images were reconstructed with OS-EM (6 iterations, 16 subsets) and with filtered backprojection (FBP), and K1, k2 and k3 images were created by the Marquardt non linear least squares method based on the 3-parameter kinetic model. Although the OS-EM activity images correlated fairly well with those obtained by FBP, the pixel correlations were poor for the k2 and k3 parametric images, but the plots were scattered along the line of identity and the mean values for K1, k2 and k3 obtained by OS-EM were almost equal to those by FBP. The kinetic fitting error for OS-EM was no smaller than that for FBP. The results suggest that OS-EM is not necessarily superior to FBP for creating parametric images. PMID- 11758947 TI - Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung. AB - OBJECTIVE: We retrospectively assessed and compared the usefulness of 11C methionine (MET)-PET with that of 18F-FDG-PET for the differentiation between benign lesions and malignant tumors of the lung. METHODS: We examined 101 patients with a suspected lung tumor including 79 patients with primary lung cancer and 22 patients with benign lesions. One hundred and forty PET studies (46 studies with MET-PET and 94 studies with FDG-PET) were performed. Both MET-PET and FDG-PET were performed on 39 patients. The MET-PET was performed 15 minutes after the administration of 67-740 MBq of MET, and FDG-PET 45 minutes after the administration of 30-437 MBq of FDG. The results were then evaluated by the standardized uptake value (SUV). RESULTS: The MET uptake in lung cancer was 3.69+/-1.22 (n = 37) which was significantly higher than that in benign lesions 1.81+/-1.04 (n = 9) (p < 0.001). The sensitivity, specificity and accuracy of MET PET were 83.8%, 88.9% and 84.8%, respectively, when 2.66 of SUV was used as the cutoff value. The FDG uptake in lung cancer was 5.94+/-2.89 (n = 75) and was also significantly larger than that in benign lesions 2.46+/-1.01 (n = 19) (p < 0.001). The sensitivity, specificity and accuracy of FDG-PET were 81.3%, 78.9% and 80.9%, respectively (cutoff = 3.20). The MET uptake in the lesions correlated significantly with FDG uptake (r = 0.71, p < 0.001). According to an ROC analysis, the area under the curve for MET-PET (area = 0. 833) was higher than that for FDG-PET (area = 0.828), but the difference was not statistically significant. Furthermore, the combined use of MET-PET and FDG-PET did not improve the diagnostic ability. CONCLUSIONS: In conclusion, both MET-PET and FDG-PET were considered to be equally useful for the differential diagnosis of lung tumors. Furthermore, MET uptake in lung lesions was found to correlate significantly with FDG uptake. PMID- 11758948 TI - Myocardial FDG-PET examination during fasting and glucose loading states by means of a one-day protocol. AB - We propose a new method to measure the myocardial FDG uptake during fasting and glucose loading in one day, a myocardial FDG-PET one-day protocol, with both 2- and 3-dimensional data acquisition (2D and 3D) without background activity subtraction. To confirm it, we evaluated the effect of scatter correction in the 2D and 3D modes of a PET scanner both in phantom and patient studies. In the phantom study, we used a cardiac phantom with six divided chambers and two cylindrical phantoms placed as the activity outside the field of view. Each chamber was filled with a different concentration of F- 18 solution. Regions of interest (ROI) were placed on a polar map generated from reconstructed images and were compared to the concentration of the solution in each chamber in both 2D and 3D. In the patient study, 10 non-diabetic patients with coronary artery disease were studied. Each patient received a myocardial FDG study during fasting (F) and glucose loading (L). L images with background subtraction (Lsub(+)) and without background subtraction (Lsub(-)) were compared by polar map analysis. The ROI counts for the true activity in 2D and 3D demonstrated a linear relationship, and quite similar slopes were observed (0.72 in 2D, 0.69 in 3D). The background fraction in Lsub(-) was 3.59+/-1.83%. There were significant differences between Lsub(-) or Lsub(+) and F in both normal and ischemic myocardium. Scatter correction was successfully performed in both 2D and 3D modes. Background activity is thought to be negligible and this proposed method is simple touse in measuring the myocardial FDG uptake in one day. PMID- 11758949 TI - Dramatic intestinal uptake of 99mTc pertechnetate in a pediatric patient with enteritis. AB - A pediatric patient with enteritis, which showed dramatically diffuse uptake of 99mTc pertechnetate in the intestine, is reported. Repeated study after medical treatment exhibited complete disappearance of the intestinal uptake. 99mTc pertechnetate scintigraphy has the potentiality for diagnosing and monitoring active enteritis. PMID- 11758950 TI - Diagnosis: myocardial ischemia due to a "steal" phenomenon caused by shunt flow of coronary-pulmonary fistulas. PMID- 11758951 TI - Detection of hepatic metastasis from medullary thyroid cancer with Tc-99m-MIBI scintigraphy in a patient with Sipple's syndrome. AB - We report a case of Sipple's syndrome with a hepatic tumor. A 28-year-old male with medullary thyroid cancer and bilateral pheochromocytomas was diagnosed as having Sipple's syndrome. The hepatic tumor was found to be hypervascular by means of a dynamic abdominal CT scan. An I-131-MIBG scan showed no increased accumulation in the tumor. A whole body Tc-99m-MIBI scan had shown, however, increased accumulation in the tumor by 10 minutes after i.v. Tc-99m-MIBI. The hepatic tumor was diagnosed histologically as a metastasis from the medullary thyroid cancer. To our knowledge, there have been no previous reports of increased Tc-99m-MIBI accumulation in hepatic metastases from medullary thyroid cancer. PMID- 11758952 TI - Tc-99m MDP, thallium-201 chloride and Tc-99m MAG3 renal uptake in subacute and chronic radiation nephritis compared. AB - The authors present a comparison of the findings for thallium-201 (Tl-201), Tc 99m MAG3 and Tc-99m MDP in subacute and chronic radiation nephritis in a 9-yr-old boy who was treated by radiation therapy for alveolar rhabdomyosarcoma of the left chest wall by a radiation port that partially included the left kidney. Tl 201 imaging three and six months later showed a cortical defect in the left kidney due to radiation nephritis. Tc-99m MDP scan showed increased uptake on both occasions, but more marked in the subacute period than in the chronic period. Tc-99m MAG3 showed decreased concentration and increased cortical retention three months later. Six months after the radiation therapy, a cortical defect corresponding to the cortical area that showed increased parenchymal retention was more prominent in the Tc-99m MAG3 scan. In the present case, Tc-99m MDP, Tl-201 and Tc-99m MAG3 findings may provide useful information for understanding pathophysiological damage in the kidney after radiation. PMID- 11758953 TI - Tc-99m MIBI imaging in malignant fibrous histiocytoma. AB - The authors report a case of malignant fibrous histiocytoma of the left forearm demonstrated by Tc-99m MIBI imaging. The tumor originated in the soft tissue of the forearm; no obvious bone invasion or metastasis was detected scintigraphically or radiologically. PMID- 11758954 TI - [18F]-FDG uptake in soft tissue dermatome prior to herpes zoster eruption: an unusual pitfall. AB - Authors report on a case of [18F]-fluorodeoxyglucose ([18F]-FDG) uptake in the soft tissue of a patient referred for [18F]-FDG coincidence detection emission tomography (CDET) in a search for recurrence of colorectal cancer. A herpes zoster eruption occurred in the same site within two days, but was spontaneously resolved. To the best of our knowledge this is the first description of a false positive [18F]-FDG result in relation to a viral infection of soft tissue. It shows that interpretation of subcutaneous foci has to be cautious in patients with or without a past history of herpes zoster even in pain-free areas and prior to skin eruption. PMID- 11758955 TI - Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping. AB - The purpose of this study was to examine whether the Tc-99m-ECD SPECT can detect any difference between the brain perfusion in patients with chronic pain and normal controls by means of the Statistical Parametric Mapping (SPM96). The subjects were twelve patients with chronic pain (CP group) and twelve normal controls (NC group). After informed consent was obtained, 720 MBq of Tc-99m-ECD was intravenously injected as a bolus. The SPECT data were acquired once for 20 mins from 5 mins after i.v. injection of Tc-99m-ECD, with a triple-head rotating gamma camera. The SPECT data were transformed into a standard stereotactic space, and group comparisons between CP and NC groups were performed on a voxel-by-voxel basis. The subset of voxels exceeding a threshold of p < 0.001 in omnibus comparisons and remaining significant after correction for multiple comparison (p < 0.05) was displayed as a volume image rendered in three orthogonal projections. There was a significant decrease in perfusion in the bilateral thalami in the CP group, suggesting that perfusion in the thalamus generally decreases in patients with chronic pain. Tc-99m-ECD SPECT with SPM96 may be useful for studies of the mechanisms of chronic pain. PMID- 11758956 TI - Simple and low-cost tele-nuclear medicine conference system with the e-mail protocol. AB - PURPOSE: Because of the recent innovative growth in computer technology, digital imaging, and the Internet, we can take advantage of these facilities for education and clinical work in nuclear medicine. We developed a tele-nuclear medicine conference system with electronic mail (e-mail) on the Internet. METHODS: Twenty-one physicians (20 radiologists, 1 neurologist), 6 technologists and 2 medical students in six university hospitals (Japan 5, Canada 1), 5 local hospitals in Japan participated in this project. We used digital still cameras (330 k pixels) equipped with a floppy disk drive and 10 x optical zoom to digitize images with JPEG compression (640 x 480 matrix). The images were attached to e-mail messages (containing a brief description of each case). The mail was sent simultaneously to all members on the mailing list. Scintigram and SPECT images as well as other radiological images were sent by e-mail. Reply mails about each case were sent to all members via the mailing list. RESULTS: During a period of 6 months, 18 cases (tumor/infection: 7, bone: 6, cardiovascular: 1, neurology; 3, endocrine: 1) with 144 e-mails (average 5.6/case) were submitted to the conference. The average period of discussion was 15.6 days. The number of attached images was 1 to 9 (average, 4.2/e-mails). JPEG compression rate was 1/10 to 1/20. The quality of the images was good enough for discussion. Some cases required additional images for further discussion. CONCLUSION: Our tele-nuclear medicine conference with an electronic mailing list and digital camera was simple and low-cost. The conference system was useful for education and clinical work. PMID- 11758957 TI - Revising the decision analysis for febrile children at risk for occult bacteremia in a future era of widespread pneumococcal immunization. AB - Previous decision analyses (DA), which have attempted to determine a superior management option for febrile children at risk for occult bacteremia, have come to different conclusions based on their underlying assumptions. Most DAs have recommended a laboratory evaluation with antibiotic treatment or have concluded that all management options are roughly the same. The purpose of this revised DA is to determine which management strategy will be superior in an anticipated era of widespread pneumococcal immunization. Decision analysis methodology comparing the following 3 management options: Obs: observation, no tests, no antibiotics; CBC+: Complete blood count (CBC) first; if the white blood cell count (WBC) >15,000, then blood culture (BC) plus antibiotics (Abx); BC+Abx: BC+Abx for all patients. Assumptions include a current bacteremia rate of 2% to 4%, and 95% of this bacteremia is caused by S. pneumococcus (which has a 15% persistent bacteremia rate) with the remainder caused by virulent bacteria (which has a 100% persistent bacteremia rate), and other assumptions made by previous decision analysis publications. Pneumococcal vaccine efficacy rates of 0%, 50%, 75%, and 100% in preventing pneumococcal bacteremia were analyzed. Overall death and neurologic sequelae rates are lower with efficacious pneumococcal vaccine. The Obs strategy is superior for all efficacy rates (including 0%) if the negative consequences of treatment are high. If the negative consequences of treatment are low, the CBC+ strategy is superior at pneumococcal vaccine efficacy rates of 50% or greater. The absolute differences between the outcomes of the 3 strategies are small, making them similar. This decision analysis indicates that widespread efficacious pneumococcal vaccine will reduce the overall morbidity and mortality associated with pneumococcal bacteremia. This favors the Obs strategy, but the superior management strategy is still dependent on an assumption of the negative consequences of treatment. Since the outcome measures for each of the management strategies are similar numerically, the strategy chosen in clinical practice may consider other factors associated with the clinical encounter such as those described. PMID- 11758958 TI - Bacterial meningitis in childhood at the Children's Hospital of Pittsburgh: 1988 1998. AB - Bacterial meningitis is an important acute infectious disease of childhood that remains a source of substantial morbidity and mortality. The impact of the Haemophilus influenzae type b (HIB) conjugate vaccines on the epidemiology of the other bacterial causes of meningitis in childhood has received little attention. The objective of this study is to report the experience at a tertiary-care children's hospital with the occurrence of bacterial meningitis before and after the licensure of the HIB conjugate vaccine. With use of International Classification of Diseases diagnostic codes for bacterial meningitis, a list of all children admitted to Children's Hospital of Pittsburgh with a primary or secondary diagnosis of meningitis due to H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis from January 1, 1988, to December 31, 1998, was constructed. Medical records were examined for basic patient demographic information including age, gender, race, bacterial etiology of meningitis, receipt of vaccine for HIB, underlying conditions, and fatalities. Two hundred twenty-one cases of bacterial meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae were identified. The age of infected children ranged from 1 month to 18 years, with a mean and median age of 38.1 months and 13 months, respectively. Fifty-two percent of the children were female, 83% were Caucasian and 16% were African-American. Before the routine use of HIB conjugate vaccine, HIB was the bacterial species responsible for the greatest proportion of cases (average of 58%/year). The absolute number of cases of bacterial meningitis attributable to HIB declined after 1991 to an average of 2.5 cases/year. The number of cases of meningitis caused by S. pneumoniae and N. meningitidis have remained relatively stable between 1988 and 1998. The case fatality rates for children with meningitis caused by H. influenzae, S. pneumoniae, and N. meningitidis were 0.0%, 9.2%, and 7.5%, respectively. Most cases of meningitis due to HIB occurred in children who had not been immunized. Three children who received the polysaccharide vaccine developed meningitis due to HIB; there were no failures of the conjugate vaccine. PMID- 11758959 TI - Pneumovax. PMID- 11758960 TI - Lactobezoars: a patient series and literature review. AB - Lactobezoar is a compact mass of undigested milk concretions located within the gastrointestinal tract. Most often found in infants, they can precipitate gastric outlet obstruction, mimicking a variety of medical and surgical conditions. A common etiology and method of cure have yet to be elucidated. A review of the literature provides some insight into causes, clinical presentations, diagnosis, and management. Data from the Medical University of South Carolina further help dispel the belief that lactobezoars are isolated to pre-term infants on caloric dense formulas. Findings suggest bezoar formation may be more common than previously thought and a high index of suspicion could help avoid costly evaluations for obstructive symptoms. PMID- 11758961 TI - Pediatric hematuria and thin basement membrane nephropathy: what is it and what does it mean? AB - Hematuria is seen frequently in the pediatric population and may signal either benign or serious renal patholosis. A significant proportion of children with asymptomatic hematuria will have thin basement membrane nephropathy (TBMN), a benign disorder, yet there is little information about this entity outside the nephrology literature. This article is designed to provide an information base for pediatric practitioners to assist them in making appropriate decisions regarding diagnosis and care. A review of experience over a decade with 9 children with biopsy-proven TBMN, including follow-up to the present; is presented. In addition, review of literature regarding TBMN, Alport's and Berger's syndromes, which comprise the major clinical entities associated with asymptomatic pediatric hematuria, is presented. Each patient was evaluated for asymptomatic, documented and persistent hematuria. Renal biopsy was performed after clinical evaluation and follow-up. TBMN and Berger's disease (IgA nephropathy) are separable only by renal biopsy results; TBMN is benign and IgA nephropathy may be progressive, mandating referral to a nephrologist. The prognosis of TBMN is excellent. PMID- 11758962 TI - An infant with cardiomegaly. PMID- 11758963 TI - Accelerated dental development as a presenting symptom of 21-hydroxylase deficient nonclassic congenital adrenal hyperplasia. PMID- 11758964 TI - Urachal web: a rare cause for recurrent abdominal pain in a child. PMID- 11758965 TI - Persistent papilledema in Ullrich-Turner syndrome treated with growth hormone. PMID- 11758966 TI - Atypical latrogenic perforation of the distal esophagus in an ELBW neonate. PMID- 11758967 TI - A new murine model of coronary artery thrombosis and role of interleukin-8 in the development of coronary thrombosis. AB - Occlusive vascular disease most often results from thrombosis superimposed on atherosclerotic plaque. In the case of an acute coronary syndrome including an acute myocardium infarction or an unstable angina pectoris thrombus in coronary artery takes significant part as known. There are few reports about animal models of acute coronary artery thrombi, because of the difficulties of operative significance. We have succeeded in making thrombus at murine coronary arteries with ferric chloride. Slight or moderate IL-8 expressions were found in the endothelial cells in the thrombus formed vessel analyzed by immunohistochemistry. The interleukin-8 (IL-8) receptor knockout mice formed the slight thrombus in coronary arteries treated with ferric chloride. We propose a role for IL-8 in the pathogenesis of acute coronary artery thrombi. This hypothesis lends itself to testing using interventions to influence IL-8 secretion and actions in the early phase of coronary thrombotic formation. PMID- 11758968 TI - Expression of PPAR(alpha) in human hepatocytes and activation by trichloroacetate and dichloroacetate. AB - Dichloroacetate (DCA) and trichloroacetate (TCA) are carcinogenic metabolites of trichloroethylene (TCE), a known hepatocarcinogen in B6C3F1 mice. This hepatocarcinogenesis is believed to result from peroxisome proliferation via PPAR(alpha) and/or stimulation of hepatocyte replication. In this study hPPAR(alpha) levels in six human liver tissues and in a long-term human hepatocyte cell line are compared. PPAR(alpha) levels varied significantly between individual tissues and are generally lower than PPAR(alpha) levels detected in mouse liver. Long-term cultured human hepatocytes display PPAR(alpha) levels only slightly lower than cultured mouse hepatocytes. Transfection studies examining the endogenous hPPAR(alpha) activity revealed little or no receptor activation, even following treatment with high concentrations of peroxisome proliferators. In contrast human hepatocytes transfected with mPPAR(alpha) and mRXR(alpha) display increased expression of PPAR(alpha), and increased PPRE reporter activity when treated with WY-14,643, TCA, and DCA. This human hepatocyte transfection system is a promising tool for examinin the regulation of genes by PPAR(alpha) from different species. PMID- 11758969 TI - Reciprocal changes in leptin and tumor necrosis factor-alpha with exercise in insulin resistant rats. AB - Leptin and tumor necrosis factor--alpha(TNF-alpha) are important mediators of insulin resistance in obese subjects through their over-expression in adipose tissue. Secretion of leptin into the circulation is a signal for the brain in patients with hyperinsulinemia. Regulation of TNF-alpha affects adipocyte insulin sensitivity and lipid accumulation. Exercise training has been suggested for the prevention and treatment of such disorders. However, how exercise modifies secretion of leptin and TNF-alpha is not known. We investigated leptin and TNF alpha in a rat model of insulin resistance induced by sucrose. After 4 weeks of sucrose feeding, 4 weeks of voluntary wheel running significantly reduced the concentrations of leptin in mesenteric (MS) and subcutaneous fat (SC) when compared to sedentary sucrose-feeding rats. These results suggest that exercise controls cytokine regulation of leptin and TNF-alpha. The increased TNF-alpha in adipose tissue may activate cytolysis for energy consumption. PMID- 11758970 TI - Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients. AB - An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis. PMID- 11758971 TI - Progression of carotid atherosclerosis and the role of endothelin in diabetic patients. AB - An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/ 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30 months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8 11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects. PMID- 11758972 TI - Regulation of gadd153 mRNA expression by hypoxia in pulmonary artery smooth muscle cells. AB - Hypoxia causes pulmonary hypertension and induces oxygen radicals in pulmonary artery smooth muscle cells (PASMCs). Since oxidative stress regulates gaddl53 expression, we examined gaddl53 mRNA in PASMCs cultured in a hypoxic environment. Gadd153 mRNA content was increased in PASMCs cultured for 24 hours in 1% oxygen. This increase was not abrogated by inhibition of protein synthesis. To explore the signaling pathways mediating hypoxic regulation of gaddl53 mRNA, the impact of calcium channel blockade by verapamil, G protein inhibition by pertussis toxin, and protein kinase C (PKC) down-regulation, was examined. Although none of these interventions reduced basal expression of gaddl53 mRNA in PASMCs, all of them suppressed the induction by hypoxia. In contrast, antioxidants had no effect. These observations indicate hypoxia induces gaddl53 expression in PASMCs through common signaling pathways. PMID- 11758973 TI - Prevention of benznidazole-induced prolonging effect on the pentobarbital sleeping time of rats using different thiol-containing compounds. AB - Benznidazole (BZ) is a nitroimidazolic chemotherapeutic agent employed against the acute and indeterminate phase of Chagas' disease, a tropical sickness afflicting more than twenty million people in Latin America. BZ has serious toxic side effects forcing people to stop treatment. These effects were attributed to the nitroreductive metabolic activation of BZ to a hydronitroxide radical or the hydroxylamine, which would covalently bind to cellular components. One of these deleterious effects is the prolongation on the pentobarbital sleeping time of rats. This results from the covalent binding of BZ reactive metabolites, arisen during its nitroreductive metabolism, to the phospholipid component of the mixed function oxidase which biotransform the barbiturate. In this study, the potential ability of different thiol containing drugs to trap BZ reactive metabolites and to prevent BZ effect on the pentobarbital sleeping time was tested. Our HPLC studies evidenced that cysteine, N-acetylcysteine, penicillamine and glutathione were able to trap BZ reactive metabolites in vitro to produce one or two adducts. Reduced lipoic acid instead, decreased the intensity of the nitroreductive process without leading to detectable adducts. The in vivo administration of the thiol drugs, at dosage regimes available in literature, was able to markedly prevent the BZ prolongation effect on the sleeping time. Whether these thiols might prevent other BZ toxic effects without harming its chemotherapeutic actions remains to be established. PMID- 11758974 TI - Enzyme activity and protein content of superoxide dismutase isozymes in human renal cell carcinoma. AB - Alterations in renal superoxide dismutase (SOD) isozymes were examined in cancerous tissues of human renal cell carcinoma and the corresponding non cancerous renal tissues. Cu,Zn-SOD activities in cancerous tissues were lower than those in normal tissues. Mn-SOD activities were varied in the cases examined, whereas no significant difference between cancerous and normal tissues was observed for Mn- or total-SOD activities. Immunoblot analysis showed that the loss in enzyme activity in cancerous tissue was greater than the decrease in protein content for either isozyme. The selective decrease in Cu,Zn-SOD activities in cancerous tissue observed in this study suggests that the cytoplasmic defense against free radical damage appears to be reduced in renal cell carcinoma. PMID- 11758975 TI - Immunosuppressive acidic protein (IAP) level used to monitor adjuvant arthritis in rats. AB - To determine if immunosuppressive acidic protein (IAP) responds to the degree of inflammation in adjuvant arthritis in rats (AA), we measured the serum IAP level of the rats by using the single immunodiffusion method, and the level of concanavalin A (Con A) binding protein by using nepherometry. Pharmacologic treatment with 0.3mg/kg of methotrexate (MTX) was done from day 5 to 14 postimmunization in rats with AA. The measured serum IAP level on day 21 indicated the most severe inflamed phase. IAP levels reflected the degree of primary and secondary inflammatory phases in AA, whereas ConA binding protein (CBP) levels did not. Our results suggest that IAP can be used to monitor the symptoms of inflammation and the efficacy of anti-inflammatory drugs. PMID- 11758976 TI - Urinary isatin concentrations in patients with Parkinson's disease determined by a newly developed HPLC-UV method. AB - Isatin, an endogenous monoamine oxidase (MAO) inhibitor, has been found in mammalian tissues. We previously reported that exogenously administered isatin significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. In order to elucidate the relationship between isatin and Parkinson's disease, we measured urinary isatin excretions in patients with Parkinson's disease using a newly developed HPLC-UV method. The recovery of this assay was approximately 102.3% at a range from 2 to 50 nmol/ml. The Coefficient of Variance (CV) for the determination at this range was approximately 2.5% for intra-assay and 6.2% for inter-assay, respectively. There was no significant difference in urinary isatin excretion between data from men and women in healthy control. The value in young age group (19-35 years old) was not significantly different compared with that of the older age group (54-84 years old). Urinary isatin levels in patients with Parkinson's disease tended to increase in accordance to the Hoehn and Yahr criteria. This is the first study in which a significant increase in urinary isatin excretion was observed at Stage III, IV and V in patients with Parkinson's disease. Urinary isatin concentrations in drug-treated patients with Parkinson's disease (at Stage I and II) tended to decrease compared with those of patients without medication. These results demonstrated that urinary isatin excretion may serve as an endogenous diagnostic marker for the clinical severity of Parkinson's disease. PMID- 11758978 TI - Interleukin-18 in patients with congestive heart failure: induction of atrial natriuretic peptide gene expression. AB - Activated inflammatory responses appear to play a role in the development of congestive heart failure (CHF). We investigated interleukin-18 (IL-18), which is a cytokine synthesized by activated macrophage, changes in patients with CHF. We evaluated 11 Japanese patients with angina pectoris (n=4) or CHF (n=7). Blood was sampled immediately after admission and at 1, 2, 3, 6, and 9 hours after admission and then every 12 hours until 5 days after admission. Plasma IL-18 concentrations were measured by an enzyme-linked immunosorbent assay. Expression of atrial natriuretic peptide (ANP) mRNA and protein synthesis was examined in cardiac myocyte by stimulation of IL-18. Plasma IL-18 concentration was significantly higher in patients with CHF than in 15 healthy volunteers (51+/-21 pg/mL, and 28+11 pg/mL, respectively, P<0.05). Increased expression of ANP mRNA was demonstrated in IL-18 treated myocytes. Protein synthesis in myocytes was increased by IL-18 in a dose-dependent manner. Increased secretion of IL-18 is induced in patients with CHF and correlates with the severity of myocardial damage and dysfunction. PMID- 11758979 TI - Adenosine A3 receptor-mediated airway microvascular leakage: role of mast cells and tachykinins. AB - To determine whether adenosine A3 receptor stimulation produces airway inflammation and, if so, what the mechanism of action is, we studied microvascular permeability in the rat trachea. After intravenous injection of Evans blue dye, adenosine and various adenosine analogues were given by inhalation, and the tracheal microvascular permeability was determined by a photometric measurement of extravasated dye. N6-2-(4-aminophenyl)-ethyladenosine (APNEA), an adenosine A3 receptor agonist, dose dependently increased plasma protein extravasation, whereas adenosine, the A1-receptor agonist N6-(R phenylisopropyl)-adenosine, or the A2-receptor agonist 5'-N-ethyl carboxamidoadenosine had no effect. The effect of APNEA was not altered by the adenosine A1/A2 receptor antagonist 8-(p-sulphophenyl)-theophylline, but was reduced by depletion of mast cell-derived mediators with compound 48/80 or pretreatment with the tachykinin NK1 receptor antagonist CP99,994. These results suggest that activation of A3 receptor specifically increase airway microvascular permeability probably via mast cell-derived mediators and tachykinins. PMID- 11758977 TI - Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. AB - Asiatic acid, a triterpene of Centella asiatica (L.) Urban (Umbelliferae), has been patented as a treatment for dementia and an enhancer of cognition by the Hoechst Aktiengesellschaft (EP 0 383 171 A2). We modified the chemical structure of asiatic acid and obtained 36 derivatives of asiatic acid in an attempt to prepare neuroprotective compounds that were more efficacious than asiatic acid itself. The neuroprotective activities of these derivatives were evaluated using primary cultures of rat cortical neurons insulted with the neurotoxin, glutamate, as an in vitro screening system. Among the semi-synthesized derivatives, three derivatives significantly mitigated the neurotoxicity induced by glutamate in this screening system. The neuroprotective activities of these 3 derivatives appeared to be more powerful than that of asiatic acid itself. These 3 derivatives significantly attenuated decreases in the levels of glutathione, glutathione peroxidase and other enzymes, which participate in the cellular defense mechanisms blunting oxidative stress. Furthermore, they significantly reduced the overproduction of NO induced by glutamate. These results showed that these derivatives of asiatic acid exerted significant neuroprotective effects on cultured cortical cells by their potentiation of the cellular oxidative defense mechanism. Therefore, these agents may prove to be efficacious in protecting neurons from the oxidative damage caused by exposure to excess glutamate. PMID- 11758980 TI - Iris-claw phakic intraocular lens for high myopia. AB - PURPOSE: To evaluate the efficacy, safety, predictability, and stability of implanting a polymethylmethacrylate (PMMA) phakic intraocular lens (PIOL) (the Artisan myopia lens) to correct high myopia. METHODS: An Artisan myopia lens was implanted in 78 consecutive eyes of 49 patients with preoperative myopia that ranged from -6.25 to -28.00 D. Mean patient age was 42.4 years. Mean follow-up was 10.7 months and all patients were followed for at least 6 months; 45 eyes had follow-up of 12 months, and 10 eyes had 24 months. The desired outcome was emmetropia in all eyes except for those eyes with preoperative myopia greater then -23.00 D. RESULTS: Fifty-three eyes (67.9%) had a postoperative refraction at the last follow-up examination within +/-1.00 D of emmetropia, and 39 eyes (50.0%) had a postoperative refraction +/- within 0.50 D of emmetropia. The postoperative refraction remained stable during the entire follow-up period. Mean spectacle-corrected visual acuity improved from 20/32 preoperatively to 20/25 postoperatively. Mean postoperative uncorrected visual acuity was 20/32. There was no significant change in endothelial cell density from baseline. We did not encounter major complications. CONCLUSION: Implantation of the Artisan myopia lens to correct high myopia resulted in a stable and fairly predictable refractive outcome. A significant endothelial cell change was not detected. PMID- 11758981 TI - Contrast sensitivity after posterior chamber phakic intraocular lens implantation for high myopia. AB - PURPOSE: To evaluate contrast sensitivity after posterior chamber phakic intraocular lens (PIOL) implantation for the correction of high myopia. METHODS: Twenty eyes of ten patients had a posterior chamber phakic intraocular lens (Staar ICL) implanted to correct high myopia. Mean preoperative myopia was 14.10+/-2.70 D. Follow-up was 24 months for all patients. Contrast sensitivity was tested with best spectacle-corrected visual acuity preoperatively and 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Contrast sensitivity increased after surgery in all spatial frequencies. Normal values were achieved for low and intermediate spatial frequencies (3 and 6 c/deg). However, in spite of the improvement, values were still below normal for high spatial frequencies (12 and 18 c/deg). When the first postoperative examination was not considered, there were no statistically significant differences in contrast sensitivity values at different postoperative periods. CONCLUSION: Contrast sensitivity increased after posterior chamber phakic intraocular lens implantation (Staar ICL) in all spatial frequencies when compared to preoperative contrast sensitivity (best spectacle corrected). PMID- 11758982 TI - Choice of spatial frequency for contrast sensitivity evaluation after corneal refractive surgery. AB - PURPOSE: To study the utility of measurements of contrast sensitivity at different spatial frequencies as an index of visual recovery following refractive surgery. METHODS: Contrast sensitivity at 1.5, 3, 6, 12, and 18 c/deg was measured with the Stereo Optical FACT chart in 20 patients after photorefractive keratectomy (PRK) using the Nidek EC-5000 excimer laser system, and in 18 patients following laser in situ keratomileusis (LASIK). Contrast sensitivity was measured preoperatively and 1, 3, 6, and 12 months after surgery. RESULTS: Results showed a statistically significant reduction (P<.01) in contrast sensitivity at all spatial frequencies in PRK patients during the first and third month, but contrast sensitivity recovered to preoperative values by 6 months after surgery (P>.1). In LASIK patients, decreased contrast sensitivity values 1 month after surgery were also obtained at all spatial frequencies. After 3 months, contrast sensitivity at 1.5 and 3 c/deg had recovered and did not differ significantly from preoperative values (P>.1), although contrast sensitivity at other frequencies remained reduced (P<.01). At 6 and 12 months, contrast sensitivity at all spatial frequencies did not differ from that obtained preoperatively (P>.1). CONCLUSIONS: Contrast sensitivity measurements at 6 and 12 c/deg appear to be most useful in the assessment of patients who have undergone laser refractive surgery because defocus and optical aberrations primarily affect the higher spatial frequencies. PMID- 11758983 TI - Monocular diplopia related to asymmetric corneal topography after laser in situ keratomileusis. AB - PURPOSE: To show a specific relationship between monocular diplopia and corneal refractive asymmetry after laser in situ keratomileusis (LASIK). METHODS: One hundred thirty-eight eyes of 98 patients who underwent LASIK for myopia between 2.12 and -17.75 D were examined under room-lighted conditions. We examined 51 eyes at 2 weeks, 46 eyes at 3 months, 32 eyes at 6 months, and 9 eyes at 1 year after LASIK. We attempted to correlate the presence of monocular diplopia with their corneal topographical features. RESULTS: Eight eyes of five patients (five eyes at 2 weeks, three eyes at 3 months after LASIK) produced symptoms of monocular diplopia. These symptomatic patients had a common corneal topographical feature caused by decentralized or inhomogeneous ablation. Every pupillary area in the patients' topographies contained steeper and flatter areas. The range of refractive power variation in these asymmetric areas was at least 1.50 D. The location of the secondary image correlated with the direction of the steeper area in all eight eyes. Pinhole viewing eliminated or reduced the prominence of secondary images in every case. CONCLUSION: Monocular diplopia following LASIK appears to correlate with postoperative corneal refractive power variation inside the pupillary area, caused by decentralized or inhomogeneous ablation. PMID- 11758984 TI - Effect of acute biomechanical changes on corneal curvature after photokeratectomy. AB - PURPOSE: Unintended hyperopic shift is a common yet poorly understood complication of phototherapeutic keratectomy (PTK) that raises fundamental questions about the etiology of corneal curvature change in PRK and LASIK. We investigated the relative contributions of ablation profile and peripheral stromal thickening to intraoperative PTK-induced central flattening, and propose a biomechanical model of the acute corneal response to central ablation. METHODS: Fourteen de-epithelialized eye bank globes from seven donors underwent either broadbeam ablation (approximately 100-microm depth, no programmed dioptric change) or sham photoablation in paired-control fashion. Peripheral stromal thickness changes and the pattern of thickness loss across each ablation zone were evaluated by optical section image analysis as predictors of acute corneal flattening. RESULTS: Relative to sham ablation, keratectomy caused significant anterior corneal flattening (-6.3+/-3.2 D, P = .002). Concomitant peripheral stromal thickening (+57+/-43 microm, P = .01) was a significant predictor of acute hyperopic shift (r = 0.68, P = .047). Ablation pattern bias did not consistently favor hyperopia and was a poor lone predictor of hyperopic shift. CONCLUSIONS: Unintended keratectomy-induced hyperopic shift is replicable in a human donor model and is associated with significant thickening of the unablated peripheral stroma. This biomechanical response may have a considerable impact on early refractive outcomes in PTK, PRK, and LASIK. PMID- 11758985 TI - Laser in situ keratomileusis for hyperopia and hyperopic astigmatism with the Nidek EC-5000 Excimer laser. AB - PURPOSE: We evaluated the efficacy, predictability, stability, and safety of laser in situ keratomileusis (LASIK) for hyperopia and hyperopic astigmatism. METHODS: A retrospective study was performed for 92 eyes of 62 consecutive patients to evaluate uncorrected (UCVA) and best spectacle-corrected visual acuity (BSCVA) and manifest refraction before and 3 and 6 months after LASIK (Moria LSK-ONE microkeratome, Nidek EC-5000 excimer laser). Eyes were divided into groups: Group 1 (low hyperopia) for spherical correction of +1.00 to +3.00 D (22 eyes), Group 2 (low hyperopic astigmatism) for toric correction with spherical equivalent refraction of +1.00 to +3.00 D (18 eyes), Group 3 (moderate hyperopia) for spherical correction of +3.25 to +6.00 D (10 eyes), and Group 4 (moderate hyperopic astigmatism) for toric correction with spherical equivalent refraction between +3.25 and +6.00 D (18 eyes). RESULTS: At 3 and 6 months after LASIK, 68 eyes (73.9%) were available for follow-up examination. Percentage of eyes with a spherical equivalent refraction within +/-0.50 D of emmetropia for Group 1 was 54.5% (12 eyes); Group 2, 50% (9 eyes); Group 3, 40% (4 eyes), and Group 4, 38.8% (7 eyes). UCVA > or =20/20 in Group 1 was 14% and in Groups 2, 3, and 4, 0%. One eye (5.5%) lost two lines of BSCVA. CONCLUSION: LASIK with the Moria LSK-ONE microkeratome and the Nidek EC-5000 excimer laser reduced low and moderate hyperopia and was within +/-0.50 D of target outcome in approximately 50% of eyes. Undercorrection was evident in all groups. The procedure was safe. PMID- 11758986 TI - Effect of photorefractive keratectomy for myopia on measurement of retinal nerve fiber layer thickness using optical coherence tomography. AB - PURPOSE: To evaluate the effect of excimer laser photorefractive keratectomy (PRK) on nerve fiber layer thickness measurements by optical coherence tomography in myopic eyes. METHODS: Twenty-two patients who had PRK for myopia underwent nerve fiber layer measurement by optical coherence tomography in both eyes before and 6 months after surgery in the first operated eye and before surgery in the fellow (control) eye, 6 months after the first PRK. Optical coherence tomography was performed with a Humphrey Optical Coherence Tomography Scanner. Each eye was scanned at the nerve head program radius of 1.5. For each of the optical coherence tomography parameters (average for each quadrant, superior, inferior, temporal, nasal; average for each clock hour; average over the entire cylindrical section), descriptive statistics were calculated. The difference between the observed change from the first to the second examination was calculated between the treated and the control eye. Individual mean differences were tested with Student's t-test. Hotelling's T-squared generalized means test was used to determine whether the set of mean differences was equal to zero. RESULTS: The average preoperative refractive error was -3.90+/-1.50 D in treated eyes and 3.89+/-1.50 D in control eyes (P = .81, Student's t-test). Mean achieved refractive correction was 3.70+/-1.70 D, corresponding to 48.1+/-22.1 microm of corneal ablation. No statistically significant difference was found in any measurement in the treated eye compared with the untreated control eye. CONCLUSIONS: At 6 months postoperatively, photorefractive keratectomy for moderate myopia that resulted in clear corneas did not affect nerve fiber layer thickness measurements, as obtained by optical coherence tomography. PMID- 11758987 TI - Microwave thermal keratoplasty for myopia: keratoscopic evaluation in porcine eyes. AB - PURPOSE: Microwave thermal keratoplasty applies microwave energy to elevate the temperature of the paracentral stroma of the cornea to its thermal shrinkage temperature of about 60 degrees C. A suitable pattern of shrinkage in the paracentral cornea can flatten the central cornea. A surface cooling system preserves the epithelium during the procedure. METHODS: Fourteen enucleated porcine eyes were treated with a prototype microwave thermal keratoplasty applicator that heated in a ring pattern with inner diameter of 3.2 mm and width of 0.7 mm. The change in corneal power was quantified by a videokeratoscope. Slit lamp microscope examinations and histological assessments were made. RESULTS: The 3-mm simulated keratometry reading showed an average of 6.60+/-6.00 D (standard deviation) of flattening. The region of opacity associated with shrinkage extended to 62% (+/-26%) of the corneal thickness. The epithelium was intact in all eyes. CONCLUSIONS: Microwave thermal keratoplasty applied in the paracentral cornea may flatten the central cornea. PMID- 11758988 TI - Confocal microscopic imaging of reticular folds in a laser in situ keratomileusis flap. AB - PURPOSE: To report the clinical and confocal microscopic characteristics of reticular folds (mudcracks) in a cornea after laser in situ keratomileusis (LASIK). METHODS: A 30-year-old male showed reticular flap folds on slit-lamp examination 1 week after LASIK. In addition to slit-lamp biomicroscopy, confocal in vivo microscopy was performed. RESULTS: Examination with a confocal white light slit-scanning microscope revealed distinct folds of Bowman's layer and underlying microfolds throughout the flap stroma. After flap re-lifting, no changes could be determined, either clinically or by confocal microscopy. At 12 months following the procedure, best spectacle-corrected visual acuity was slightly improved, but the folds, as imaged by confocal microscopy, still persisted. CONCLUSIONS: In the present case, reticular folds after LASIK involved the entire thickness of the flap. Simple flap lifting was not sufficient for smoothing out the folds. PMID- 11758989 TI - Soft contact lenses for irregular astigmatism after laser in situ keratomileusis. AB - PURPOSE: To investigate soft contact lenses for managing irregular astigmatism after laser in situ keratomileusis (LASIK). The prevailing notion has been that soft contacts conform to corneal surface irregularities and have a limited role for managing LASIK-induced irregular astigmatism. METHODS: A 41-year-old man with bilateral central steep islands following LASIK had best spectacle-corrected visual acuity of 20/40(+1) in the right eye and 20/70+2 in the left eye, despite 20/20 acuity in each eye with rigid contact lenses. Three soft lenses made of etafilcon A (58% H2O) in different center thicknesses were placed sequentially on each eye. All lenses were -2.00 D sphere, in the flatter of the two available base curves. With each lens, corneal topography, spherical over-refraction, and the resulting visual acuity were recorded. RESULTS: In all instances, corneal topography showed reduced surface irregularity although at least some irregularity still transmitted through the lenses. Each spherical over-refraction gave better visual acuity than the corresponding best spectacle-corrected visual acuity. The right eye achieved 20/20 with the thickest lens and spherical over refraction. The left eye achieved 20/25 with the lens of intermediate thickness and spherical overrefraction. The patient reported functional vision and good comfort with these lenses. CONCLUSIONS: Disposable soft contact lenses can modestly mask irregular astigmatism caused by excimer laser ablation. PMID- 11758990 TI - Experimental model of corneal haze in chickens. AB - PURPOSE: To develop an experimental animal model of corneal haze following photorefractive keratectomy (PRK). METHODS: Fifteen Iber Braun hens underwent unilateral PRK for -9.00 D of myopia. The animals were sacrificed at 1, 3, and 6 months postoperatively, and light microscopy was performed. RESULTS: Slit-lamp microscopy showed haze in the PRK-treated eyes. Histopathologic study disclosed epithelial hyperplasia, basement membrane abnormalities, and extensive anterior stromal disorganization. CONCLUSIONS: An easy and inexpensive model of haze after PRK was developed in an animal with Bowman's layer. This new model could be useful to understand the pathophysiology and pharmacologic modulation of corneal haze. PMID- 11758991 TI - Ayala wins 2001 Troutman Award. PMID- 11758992 TI - Analysis of aggregate surgically induced refractive change, prediction error, and intraocular astigmatism. PMID- 11758993 TI - Present status of asbestos mining and related health problems in India--a survey. AB - At present in India more than thirty mines are in operation. It produces 2800 tones of asbestos per month (mainly chrysotile and tremolite) and in recent years substantial quantity (-70%) is imported from Canada. The quality of asbestos produced in India is very poor. The mining and milling and other related processes expose the people to cancer and related diseases. Women are more affected by their exposure in processing unit compared to male who are generally working in mines. Direct and indirect employment in asbestos related industry and mine is around 100,000 workers. Latency period (length of the time between exposure and the onset of diseases) in India is estimated to be 20-37 yr. The causes for lung and breathing problem are mainly due to obsolete technology and direct contact with the asbestos products without proper precaution, because in India asbestos are sold without statutory warning. This paper reviews health effects (such as fibrosis, sequelae, bronchogenic cancer, and malignant mesothelioma) on the Indian mine workers caused due to asbestos mining related activities with respect to their present day condition. PMID- 11758994 TI - Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal brush border membrane vesicles (BBMV): cisplatin-intoxicated rats. AB - Platinosis with severe dermatitis and/or asthma is broadly defined as the effects of soluble platinum salts on people exposed to them occupationally. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin, the most useful agent, is limited by the development of nephrotoxicity. Thus, an accidental exposure to soluble platinum at a high dose in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous studies, we found that the preincubation of rat renal brush border membrane vesicles (BBMV) with cisplatin and carboplatin, a second-generation platinum coordination complex, significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we performed in vivo experiments in cisplatin-intoxicated rats to elucidate the toxic mechanism of cisplatin. And our results showed that the citrate uptake was significantly inhibited in cisplatin-intoxicated rats at 1 min compared with that of control rats. PMID- 11758995 TI - Moderate alcohol consumption reduces urinary 8-hydroxydeoxyguanosine by inducing of uric acid. AB - Recent studies suggest that moderate alcohol consumption is associated with a low risk of cancer, coronary heart disease, and other diseases. Most of these diseases are considered to be related to the action of reactive oxygen species (ROS) at certain stages of disease progression. However, considerable evidence exists indicating that ethanol generates ROS in vivo. Thus, the reduced risk of disease as a result of alcohol consumption seems to contradict evidence suggesting the induction of ROS by ethanol. In the present study, we investigated whether oxidative stress was induced in moderate alcohol drinkers. We measured the total urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG) levels as a systemic oxidative stress marker and an oxidative DNA damage marker, respectively. Serum uric acid was also measured as an alcohol-induced antioxidant. We compared total urinary biopyrrins and 8-OHdG levels among groups with different alcohol habits. The results showed that total biopyrrins levels increased with the amount of alcohol consumed, but that the level of 8-OHdG significantly decreased with the amount of alcohol consumed. The decrease in 8 OHdG levels seemed to be associated with increasing levels of uric acid. Judging from the increasing level of total biopyrrins, alcohol may induce ROS. ROS may then cause cell damage in liver, as suggested by the positive correlation between the total biopyrrins levels and the serum GOT, GPT, and gammaGTP levels. However, since ROS may be more effectively counteracted by uric acid in organs other than the liver, DNA damage may be suppressed rather than induced. Accordingly, moderate alcohol consumption seems to have the overall effect of reducing DNA damage, as shown by the decrease in urinary 8-OHdG levels observed in our study. PMID- 11758996 TI - Biological monitoring of exposure to benzene in petrol pump workers and dry cleaners. AB - Exposure to benzene has been monitored in petrol-pump workers and dry cleaners of Meerut City (India) by measuring phenol content of their urine samples. Average values for phenol in urine were higher in petrol-pump workers than dry cleaners. Alcoholic subjects excreted more phenol than smokers and non-vegetarians. It is concluded that alcohol can alter the susceptibility of man to benzene toxicity by affecting its metabolism. PMID- 11758997 TI - Elevated interleukin-4 and interleukin-6 in rats sensitized with toluene diisocyanate. AB - In order to investigate the cytokine profile in toluene diisocyanate (TDI) induced occupational asthma, we conducted a quantification of cytokine production in a murine model of respiratory hyperreactivity to TDI. Wistar rats were sensitized with intranasal application of 10% TDI and provoked with 5% TDI to induce airway hypersensitivity. The blood leucocytes were counted, and bronchoalveolar lavage (BAL) was performed and the cellular responses in BAL fluid were analysed. Lung histological examination was performed to investigate the inflammatory status in the airway. The production of IL-2, IL-4, IL-6 and IFN gamma in serum, BAL fluid and spleen cell were determined with ELISA kits. The cellular results demonstrated that neutrophils and eosinophils in blood were significantly increased and the total cells and each different cell, in particular eosinophils in BAL fluid were markedly increased in TDI sensitized rats. Histological analysis showed that a respiratory inflammation represented by prominent infiltration of eosinophils in central and peripheral airways was present in TDI-sensitized rats. The cytokine assays revealed that in TDI sensitized rats, IL-4 was predominately secreted in serum, and IL-4 and IL-6 rather than IL-2 and IFN-gamma were predominately secreted in BAL fluid and in spleen cell. These findings suggested that IL-4 and IL-6 are preferentially produced and may have an important role in occupational asthma induced by TDI. PMID- 11758998 TI - Relationships between chemical structures and mutagenicity: a preliminary survey for a database of mutagenicity test results of new work place chemicals. AB - A database of mutagenicity test results of new chemicals has been developed. Based on the amendment of the Industrial Safety and Health Law (ISHL) in 1979, manufacturers and importers in Japan are required to register any new work place chemicals with bacterial mutagenicity test results. At present more than ten thousand substances have been examined. We have surveyed correlations between 44 substructures and mutagenicity in 2,857 ISHL data as well as in 1,207 National Toxicology Program data as a preliminary analysis. The percentages of the mutagenic compounds were calculated. High percentages were found for electrophilic reagents such as epoxides (63%), aromatic nitro compounds (49%) and primary alkyl monohalides (46%). 71% of peroxides was found to be mutagenic. The results suggest that several types of reactions such as nucleophilic substitution reaction, nitrenium cation reaction and radical reaction are included in the process of the mutagenic alterations of DNA. PMID- 11758999 TI - Occupational contact urticaria caused by airborne methylhexahydrophthalic anhydride. AB - Acid anhydrides are low-molecular weight chemicals known to cause respiratory irritancy and allergy. Skin allergy has on rare occasions been reported. A total of 3 subjects with occupational exposure to methylhexahydrophthalic anhydride (MHHPA) and hexahydrophthalic anhydride (HHPA) from an epoxy resin system were studied to evaluate the nature of their reported skin and nose complaints (work related anamnesis, specific IgE, contact urticaria examinations, and ambient monitoring). Using a Pharmacia CAP system with a HHPA human serum albumin conjugate, specific IgE antibody was detected in serum from 1 (33.3%) out of the 3 workers. One unsensitized worker displayed nasal pain and rhinorrhea only when loading liquid epoxy resins into the pouring-machine (2.2 mg MHHPA/m3 and 1.2 mg HHPA/m3), probably being an irritant reaction. Two workers had work-related symptoms at relatively low levels of exposure (geometric mean 32-103 microg MHHPA/m3 and 18-59 microg HHPA/m3); one complained of only rhinitis, and the other was sensitized against HHPA and displayed both rhinitis and contact urticaria (the face and neck). The worker's skin symptoms were evidently due to airborne contact, since she had not had any skin contact with liquid epoxy resin or mixtures of MHHPA and HHPA. These urticaria symptoms were confirmed by a 20 min closed patch test for MHHPA, but not by that for HHPA. The causative agent was considered to be MHHPA, although the specific IgE determination to MHHPA was not performed. PMID- 11759000 TI - Three cases of acute methyl bromide poisoning in a seedling farm family. AB - We encountered three patients (Patient I: 39-year-old man, Patient II: 34-year old woman, and Patient III: 5-year-old girl) with acute methyl bromide poisoning, which had occurred as a result of exposure to the gas that leaked from methyl bromide cans stored in a warehouse of a seedling farm. Since all three patients exhibited almost the same initial symptoms, i.e., severe vomiting, tonic convulsions and clouding of consciousness, botulism was suspected at first. However, subsequent inquiry revealed that 27 cans of methyl bromide had been stored in the building that the patients lived in, and that the cans had been damaged a few days before the onset of the patients' illness by a thrashing machine that was being moved by them to another location. Inspection revealed that all the cans of methyl bromide had passed the expiry date and were corroded. Even though none of the cans had been used, three cans with a capacity of 750 g were found to be empty. Plasma bromide ion concentrations were determined to be high (72.9 microg/ml, 67.8 microg/ml and 91.5 microg/ml; normal level, < 5 microg/ml), and acute methyl bromide poisoning was diagnosed 8 days after admission of the patients to the hospital. Hemodialysis (peritoneal lavage in the case of the child) was performed immediately, after which the plasma bromide ion concentrations returned to normal and the general condition of the patients gradually improved. PMID- 11759001 TI - Community-focused partnering. PMID- 11759002 TI - Dental work force in China. PMID- 11759003 TI - Gene expression in a pure population of odontoblasts isolated by laser-capture microdissection. AB - Studies of odontoblast differentiation and function have been limited due to difficulties in obtaining sufficient numbers of intact cells. We describe a novel approach of laser-capture microdissection to obtain homogenous populations of pre odontoblasts and odontoblasts from tissue sections of mouse molar cusp tips. Fixation, processing, and staining conditions were assessed for the optimal retrieval of total RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA from three-day-old captured odontoblasts was sufficient in quantity and quality. Odontoblast-specific gene expression was studied by RT-PCR analysis performed in a single streptavidin coated tube. At E15.5, Days 0 and 3, gene expression in laser-captured odontoblasts resembled that seen in vivo by in situ hybridization. The use of LCM is thus a valuable means of retrieving quality RNA from discrete populations of odontoblasts at different stages of dentinogenesis. PMID- 11759004 TI - Regulation of tooth development by the novel type I TGFbeta family member receptor Alk8. AB - We have recently identified, in zebrafish, a novel type I receptor of the TGFbeta family, alk8, that participates in Bmp signaling pathways to mediate early dorsoventral patterning of neurectodermal and mesendodermal tissues. Since Bmps play significant roles in tooth specification, initiation, and differentiation, we hypothesized that alk8 may play a role in directing the Bmp-mediated epithelial mesenchymal cell interactions regulating tooth development. Immunohistochemical analysis demonstrates that Alk8 is expressed in developing zebrafish and mouse teeth. Examination of tooth development in zebrafish with disrupted alk8 signaling revealed specific defects in tooth development. Ectopic expression of constitutively active Alk8 results in the formation of elongated tooth structures, while expression of dominant-negative Alk8 results in arrested tooth development at the bud stage. These results are consistent with the established requirements for Bmp signaling in tooth development and demonstrate that Alk8 is a key regulator of tooth development. PMID- 11759005 TI - Sonic hedgehog regulates epithelial proliferation and cell survival in the developing tooth germ. AB - Shh expression is highly restricted to the future sites of tooth development during the initiation of odontogenesis. This suggests a role for Shh as a proliferative factor, as localized epithelial thickenings invaginate to form a tooth bud. We have investigated this role by blocking Shh signaling between E10.5 and E12.5 in murine mandibular processes using a 5E1 blocking antibody and the PKA activator Forskolin. This results in down-regulation of Ptc, a principle target of Shh signaling. The effects of inhibition varied with developmental time. At E10.5, tooth development was arrested as epithelial thickenings and the numbers of teeth developing were considerably reduced. Inhibition at E12.5 produced localized apoptosis in the epithelium at the tip of the tooth buds, although some teeth were able to develop. Thus, Shh has dual roles in early odontogenesis, first in bud formation by stimulating epithelial proliferation, and second in the development of cap-stage tooth germs by increasing epithelial cell survival. PMID- 11759006 TI - Crown morphology and pattern of odontoblast differentiation in lower molars of tabby mice. AB - The Tabby mutation leads to abnormal crown morphology in the developing molars. To identify cusps which were altered in number, size, and position in the first lower molars of mutant mice, we analyzed the patterning of odontoblast differentiation using morphological criteria on serial sections and 3D reconstructions. In wildtype mice, polarized and functional odontoblasts were first observed in the median L2 and B2 cusps, then in the distal cusps L3 and B3, and finally in L1, B1, and 4. In Tabby mice, terminal differentiation of odontoblasts was retarded by 24-36 hours compared with wild-type mice. Polarized odontoblasts first appeared in the most mesial part of the tooth and progressively extended distally. The mesial part of the M1 in Tabby fetuses may correspond to the L2, B2 area from wild-type mice. The ante-molar dental primordium observed in some samples would thus represent remnants of cusps L1 and B1. PMID- 11759007 TI - Topographic changes of focal adhesion components and modulation of p125FAK activation in stretched human periodontal ligament fibroblasts. AB - Mechanical stress has been shown in vitro to modulate integrin-beta1-mediated activation of p125FAK/FAK. To test the hypothesis whether this also applies to periodontal ligament fibroblasts (PDLs), we subjected human PDLs to mechanical stretch and analyzed stress-induced changes of p125FAK activation by quantitative immunoprecipitation of p125FAK and changes in the topography of molecules localizing in focal adhesions by indirect immunofluorescence. Generally, all components of focal contacts under study-including detection of phosphotyrosine, i.e., integrin-beta1, p125FAK, and paxillin-revealed a relative co-localization during stretch application. Under stretch, we observed a re-distribution of all components from the cell periphery to the cytoplasm following the main axes. Tyrosine phosphorylation of p125FAK was monitored up to 72 hours under stretch. While the amount of p125FAK remained essentially constant, the activation of p125FAK was clearly modulated. Tyrosine phosphorylation of p125FAK increased from 15 minutes up to 1 hour and declined after stretching periods of 24, 48, and 72 hours. The analysis of our data indicated a stretch-induced redistribution of focal adhesion components and a modulation of p125FAK activation, suggesting alterations in focal adhesions and their associated signal cascade. PMID- 11759008 TI - Dantrolene counteracts the masseter muscle damage induced by artificial occlusal wear: studies in a rat model. AB - In previous studies, we showed that the introduction of occlusal alterations to rats results in masseter muscle abnormalities. Here, we investigate whether administration of the muscle relaxant dantrolene to rats with occlusal alteration could counteract the occurrence of such abnormalities. Rats underwent unilateral amputation of molar cusps to cause malocclusion. Some rats received dantrolene (10 mg/kg/day subcutaneously). The masseter muscles ipsilateral to the amputated molars were excised 26 days later. Sham-operated rats were used as controls. The tissue samples were studied by light and electron microscopy and morphometry. Moreover, tissue Ca2+ content, an index of muscle injury, was determined. In the absence of dantrolene, occlusal alteration leads to microvessel constriction, morphologic damage of masseter muscle fibers and blood capillaries, and elevation of tissue Ca2+ content. These changes were nearly abrogated by dantrolene, thus supporting it as a possible new therapeutic tool for the treatment of malocclusion-induced muscle diseases. PMID- 11759009 TI - Acetylcholine-induced vasodilation of isolated pulpal arterioles. AB - The presence of cholinergic mechanisms in the control of pulpal microcirculation has been a controversial issue. In this study, we aimed to determine the direct vasoactive responses of isolated pulpal arterioles to acetylcholine, and to investigate whether such responses are endothelium-dependent. Using an in vitro micro-perfusion system, we isolated pig pulpal arterioles, cannulated and perfused them intraluminally, and monitored the diameter. Following equilibration, the vessels were contracted with 10(-5) M noradrenaline, and the effect of increasing doses of acetylcholine was determined. The influence of the muscarinic antagonist, atropine, or the loss of endothelial cell function following saponin treatment was also determined. Acetylcholine induced a dose dependent vasodilation, reaching 94.6+/-1.4% (n = 22) of the uncontracted diameter at 10(-4) M. The vascular relaxation effect of acetylcholine was abolished in the presence of atropine, and by saponin treatment. Analysis of these data suggests that, in the pig, the acetylcholine-induced vasodilation of incisor pulpal arterioles is endothelium-dependent and mediated by muscarinic receptors. PMID- 11759010 TI - Identification of cariostatic substances in the cacao bean husk: their anti glucosyltransferase and antibacterial activities. AB - The cacao bean husk has been shown to possess two types of cariostatic substances, one showing anti-glucosyltransferase (GTF) activity and the other antibacterial activity, and to inhibit experimental dental caries in rats infected with mutans streptococci. In the present study, chromatographic purification revealed high-molecular-weight polyphenolic compounds and unsaturated fatty acids as active components. The former, which showed strong anti-GTF activity, were polymeric epicatechins with C-4beta and C-8 intermolecular bonds estimated to be 4636 in molecular weight in an acetylated form. The latter, which showed bactericidal activity against Streptococcus mutans, were determined to be oleic and linoleic acids, and demonstrated a high level of activity at a concentration of 30 microgram/mL. The cariostatic activity of the cacao bean husk is likely caused by these biologically active constituents. PMID- 11759012 TI - Experimental gingivitis in women using oral contraceptives. AB - Oral contraceptives (OC) have historically been considered a risk factor for gingival diseases. We set out to investigate this premise further, given that, over recent years, hormone concentrations in OC have been substantially reduced. Using a prospective, split-mouth, experimental gingivitis model, pre-menopausal women either taking (n 14) or not taking (n = 16) OC refrained from all oral hygiene practices in one maxillary (test) quadrant while continuing to perform normal oral hygiene activities in the contralateral (control) quadrant. Mean increases in plaque index (PI), gingival index (GI), and gingival crevicular fluid (GCF) volume from days 0 to 21 were significant in test quadrants (P < 0.05) but did not differ regardless of whether subjects received OC (P > 0.05). PI, GI, and GCF volume did not vary in control quadrants over the course of the study (P > 0.05). Analysis of these data suggests that current OC formulations do not affect the inflammatory response of the gingiva to dental plaque. PMID- 11759011 TI - The association of bacterial adhesion with dental caries. AB - Saliva adhesion of bacteria is a key event in oral biofilm formation. Here, we used partial least-squares (PLS) analysis to correlate adhesion of cariogenic (Streptococcus mutans Ingbritt) and commensal (Actinomyces naeslundii LY7) model bacteria, and their agglutinin and acidic proline-rich protein ligands, respectively, with high and low caries experiences in 38 children reflecting today's skewed caries distribution. Adhesion of S. mutans was among the factors correlating strongest with high caries experience when PLS modeled together with traditional factors (e.g., sugar intake, lactobacilli counts). Saliva phenotypes with high agglutinin levels and Db-s (an acidic PRP variant) coincided with both high caries experience and S. mutans adhesion. A. naeslundii adhesion correlated with low caries experience. Non-Db phenotypes (i.e., acidic PRP-1 and PRP-2 variants) coincided with both low caries experience and S. mutans, but high A. naeslundii, adhesion. Thus, bacterial adhesion may modulate susceptibility and resistance to dental caries. PMID- 11759013 TI - Kaplan-Meier analysis of dental implant survival: a strategy for estimating survival with clustered observations. AB - The study's purposes were to estimate dental implant survival in a statistically valid manner and to compare three models for estimating survival. We estimated survival using three different statistical models: (1) randomly selecting one implant per patient; (2) utilizing all implants, assuming independence among implants from the same subject; and (3) utilizing all implants, assuming dependence among implants from the same subject. The cohort was composed of 660 patients who had 2286 implants placed. Due to the high success rates of implants, the five-year survival point and standard error estimates varied little among the three models. Patients at high risk for implant failure (smokers) manifested greater variation in the standard error estimates among the three models, 8.2%, 4.0%, and 5.6%, respectively. To obtain statistically valid survival confidence intervals when performing Kaplan-Meier survival analyses, we recommend adjusting for dependence when there are multiple observations within the same subject. PMID- 11759014 TI - Movement of teeth adjacent to posterior bounded edentulous spaces. AB - Bounded edentulous spaces (BES)-a missing posterior tooth with intact adjacent teeth-are thought to lead to arch collapse resulting from the movement of adjacent teeth. To determine the rate of change in distance between teeth adjacent to a BES, we examined three successive measurable radiographs of 116 untreated posterior BES cases. The distance between the teeth (DBT) adjacent to the space was measured, and change in DBT (delta DBT) between pre-extraction and follow-up radiographs was calculated. We used linear spline regression to construct models for tooth movement and to identify factors associated with delta DBT. The mean delta DBT was < 1 mm during the first year post-extraction, and the DBT continued to decrease at a successively slower rate each following year. Overall and for each tooth type, the greatest rates of decrease in DBT were seen in the zero to two-year period. In a multivariable model, time since extraction and tooth type were significantly associated with delta DBT. These findings suggest that movement of teeth adjacent to a posterior BES after the first two years is usually gradual and minor within the time frame of this study. PMID- 11759015 TI - Cell-interactive alginate hydrogels for bone tissue engineering. AB - There is significant interest in the development of injectable carriers for cell transplantation to engineer bony tissues. In this study, we hypothesized that adhesion ligands covalently coupled to hydrogel carriers would allow one to control pre-osteoblast cell attachment, proliferation, and differentiation. Modification of alginate with an RGD-containing peptide promoted osteoblast adhesion and spreading, whereas minimal cell adhesion was observed on unmodified hydrogels. Raising the adhesion ligand density increased osteoblast proliferation, and a minimum ligand density (1.5-15 femtomoles/cm2) was needed to elicit this effect. MC3T3-E1 cells demonstrated increased osteoblast differentiation with the peptide-modified hydrogels, as confirmed by the up regulation of bone-specific differentiation markers. Further, transplantation of primary rat calvarial osteoblasts revealed statistically significant increases of in vivo bone formation at 16 and 24 weeks with G4RGDY-modified alginate compared with unmodified alginate. These findings demonstrate that biomaterials may be designed to control bone development from transplanted cells. PMID- 11759016 TI - Kinematic modeling of jaw-closing movement during food breakage. AB - It has been demonstrated that the vertical jaw movement trajectories during gum chewing can be explained by jerk-cost minimization. However, it is uncertain whether the masticatory jaw movement in space can be predicted by the minimum jerk model. The aims of the present study were to develop minimum-jerk models that would explain 3D masticatory jaw movements with different hardnesses of foods, and to evaluate if the models can predict the movements accurately. The 3D masticatory jaw movement during food breakage was formulated for two types of test foods. The coefficients of determination (R2) between the measured and model based values ranged from 0.846 to 0.882. Differences were found in the kinematic parameters between the test foods. The results suggest that the models predict the 3D jaw movements during food breakage and are effective in differentiating among the kinematic features of masticatory jaw movements that are peculiar to the mechanical properties of foodstuffs. PMID- 11759017 TI - Hospital hygiene procedures: areas of consensus and ongoing controversies. Proceedings of the 6th International BODE Hygiene Days, 7-10 September 2000, Vienna, Austria. PMID- 11759018 TI - Some principles of virucidal testing. AB - Disinfection measures for the interruption of viral infection chains must use chemical substances with proven virucidal efficacy. Therefore, tests of disinfectants with model viruses in suspension and carrier tests are urgently necessary to enable clear recommendations to be made for concentrations and contact times. PMID- 11759019 TI - Hepatitis A virus: a test method for virucidal activity. AB - Hepatitis A virus (HAV) is closely related to the genus enterovirus. HAV is very stable and resistant to acid pH and elevated temperature, as well as to chemicals and environmental influences. Human poliovirus is still one of the model viruses for testing disinfectants but there are discussions about changing to hepatitis A virus. The purpose of this study was to develop a method for using adapted hepatitis A virus to test hand disinfectants. Using HAV strains HM175/24a and FRhK-4 cytopathic effects were visible rarely, and not before 14 days. To verify virus growth in cells a RT-PCR was developed. Two disinfectants tested did not show the required virucidal activity to satisfy current German guidelines. PMID- 11759020 TI - Hand hygiene--comparison of international recommendations. AB - The value of hand hygiene for the prevention of cross-infection was first observed in the middle of the 19th century. Since then, which procedure is the most suitable for hand hygiene has been repeatedly discussed and several different guidelines and recommendations have been published. The aim of this review is to compare different recommendations for hand hygiene regarding technique and indication. Medline, the internet and a personal library were searched to obtain as many written recommendations as possible. In addition, a small questionnaire was sent by e-mail to 20 international colleagues. As a result, written recommendations from 10 countries could be compared. Recommended methods of hand hygiene include handwashing (washing hands with plain soap), hygienic handwash (washing hands with medicated soap) and hygienic hand-rub (use of antiseptic rubs). In most countries handwashing and hygienic handwash are the methods of choice and only in central European countries is hygienic hand-rub the preferred technique. Situations in which performance of hand hygiene is recommended are comparable. However, no single indication is recommended in all guidelines. Hand hygiene is most often recommended before performing invasive procedures and after microbial contamination. Guidelines should be clear and easy to follow for them to become standard of care. Thus, guidelines are needed that do not leave to the health care worker a decision as to whether hand hygiene is indicated. PMID- 11759021 TI - Assessment of the activity of antiperspirants added to surgical hand disinfectants: methodological aspects and first observations. AB - Due to the risk of sensitization caused by glove powder, the use of unpowdered latex gloves is increasing. These unpowdered gloves need a special inner-surface layer which makes it easier for the applicant to put the glove on the hand and to remove it again. However, many users report difficulties with removing the gloves because of sweat production within the glove. Therefore, a method has been developed to evaluate the efficacy of antiperspirants which may be added either to the inner-surface layer of the glove or to hand disinfectants or to skin-care products used before the gloves are put on. The paper describes various trials to optimize this method. PMID- 11759022 TI - Hand antiseptics: rubs versus scrubs, alcoholic solutions versus alcoholic gels. AB - This report describes three different investigations undertaken to demonstrate the advantage of fluid alcoholic hand disinfectants. In the first study, the skin compatibility of Sterillium, a liquid alcoholic rub-in hand disinfectant was compared with that of Hibiscrub, a water-based handwashing antiseptic. Using various parameters such as image analysis of removed squames (D-squames), skin roughness or transepidermal water loss, Hibiscrub was found to be significantly inferior to Sterillium. Hibiscrub caused skin irritation in 15 volunteers who could not complete the test. In a second study, the microbicidal efficacy of Sterillium and Hibiscrub was tested in surgical hand disinfection. The microbial reduction by Sterillium was significantly greater than that of Hibiscrub, immediately after application as well as after the surgical procedure. In a third study, certain alcoholic gels were tested according to the EN 1500 'hygienic hand disinfection'. None of the gels tested passed the EN 1500 within 30s. However, Sterillium met the EN 1500 requirement within 30s. We conclude that Sterillium is superior to Hibiscrub in terms of skin tolerance and microbicidal efficacy in surgical hand disinfection. It is also superior to alcoholic gels. PMID- 11759023 TI - Does hand care ruin hand disinfection? AB - Hand washing and hand disinfection put considerable stress on the skin thus requiring specific hand care. It is important however that the care products do not impair the effect of hand disinfectants. We therefore investigated the interaction of two hand care products (oil-in-water and water-in-oil emulsions) on the microbicidal efficacy of different alcoholic hand-rubs, using the contamination model described in EN 1500. The mean log10-reduction factors for three hand-rubs varied between 4.03 and 4.22 compared with 3.76 and 4.43 for six possible combinations of hand-rubs and hand care products applied immediately prior to disinfection. Differences between reduction factors achieved with hand rubs alone and in combination with hand care were not significant. Repeated application of care products with subsequent hand disinfection also did not result in significantly lower reduction factors than achieved with hand disinfection alone. Our data suggest that administration of selected products for hand care does not necessarily impair hand disinfection and is therefore recommended for occupational health as well as for infection control reasons. PMID- 11759024 TI - Arguments for alcoholic hand disinfection. AB - The non-aqueous use of ethanol or propanols offers various advantages over washing hands with either unmedicated or medicated soap in both hygienic and surgical hand disinfection. Alcohols exert the strongest and fastest activity against a wide spectrum of bacteria and fungi (but not bacterial spores) as well as enveloped (but less so against non-enveloped) viruses, being little influenced by interfering substances. They are of low toxicity and offer acceptable skin tolerability when made up with suitable emollients. The mode of their application is simple and three to four times more economical of time than wash procedures, features which help to increase the compliance with the rules of hand hygiene. PMID- 11759025 TI - Compliance with hand disinfection and its impact on hospital-acquired infections. AB - Hand hygiene prevents cross-infection in hospitals, but adherence to guidelines is poor among healthcare workers. Although some interventions to improve compliance have been successful, none had achieved lasting improvement until very recently. Reasons for non-compliance with recommendations occur at individual, group and institutional levels. The complexity of the process of behavioural change would suggest that the application of multimodal, multidisciplinary strategies are necessary. Both easy access to hand hygiene in a timely fashion and skin protection appear necessary prerequisites for satisfactory hand hygiene behaviour. Alcohol-based hand-rub may be superior to traditional handwashing as it requires less time, acts faster, irritates hands less often, and recently proved significantly to contribute to sustained improvement in compliance associated with decreased infection rates. This paper reviews barriers to appropriate hand hygiene and describes the results of the first successful experience of sustained hand hygiene promotion and its effectiveness on hospital acquired infection. PMID- 11759026 TI - Handwashing practices in Polish hospitals: results of a survey conducted by Polish Society of Hospital Infection. AB - Handwashing is the most important and least expensive measure for preventing transmission of hospital-acquired infections. Nevertheless, healthcare workers do not seem to understand the risks associated with non-compliance. Thus, compliance is usually poor and rarely exceeds 40%. The Polish Society of Hospital Infection has made a short study of handwashing practices in Polish hospitals as observed by members of infection control teams. The study was based on questionnaires given to infection control workers attending the annual congress of the society. The workers were asked to complete the forms during the congress according to their perceived estimations. Altogether 78 complete questionnaires were analysed. The responding staff members were from hospitals of all sizes, reference levels and regions. Nearly all (95.6%) hospitals had a written protocol for handwashing procedures but according to the estimates of their infection control teams, the compliance rates varied from 20 to 80% although in most institutions was between 40% and 60%. In the vast majority of the hospitals, alcoholic rub preparations were used (70.3%), but in some both handwashing with chlorhexidine in detergents and alcohol-based antiseptics were used in different situations. According to the respondents, the mean time of hand disinfection varied from 1 to 3 min. The handwashing procedures were mostly performed in examination, operating and patients' rooms. Thus, it seems that as in other countries, Polish healthcare workers fail to understand the importance of handwashing. PMID- 11759027 TI - Role of the clinical microbiology laboratory in infection control--a Danish perspective. AB - Clinical microbiology laboratories in Denmark are located in hospitals and staffed by clinical microbiologists who are clinically trained medical doctors. Each county has its own clinical microbiology unit, serving a population of 0.3 0.6 million. The responsibilities of clinical microbiology unit cover many different aspects of infection control. They include detection of outbreaks of hospital-acquired infections, screening for multi-resistant organisms, advice to clinicians about disinfection, sterilization and isolation procedures, and the rational use of antibiotics. Clinical microbiologists work closely with infection control nurses. Together they form the infection control team, which is the executive part of the local infection control committee. The infection control team is also the main body responsible for the development of guidelines, which are approved by the regional infection control committee. The local microbiology laboratories work in close contact with the National Department of Hospital Hygiene and other reference laboratories at the State Serum Institute. The present structure of infection control was established 25 years ago. The main aim at that time was to decentralize infection control and establish facilities as close to clinicians and patients as practically possible. This has solved most basic problems related to infection control, and compliance by clinicians has been fairly good. However, the present organization will not meet future requirements for standardization and documentation of quality. Currently a national standard for infection control is being prepared. It consists of a main standard defining requirements for the management system and 12 subsidiary standards defining requirements for specific areas of infection control. Adoption of the standard will undoubtedly require additional resources for infection control at a local level, and some organizational changes may also be needed. Infection control should be maintained as an integrated part of clinical microbiology. PMID- 11759028 TI - Handwashing compliance in a French university hospital: new perspective with the introduction of hand-rubbing with a waterless alcohol-based solution. AB - The baseline compliance with handwashing in a French university hospital was as low as the compliance rates reported in other countries, i.e., less than 50%. By introducing the use of hand-rubbing with an alcoholic solution, as a substitution method for both handwashing with soap and handwashing with an antiseptic agent, we significantly improved hand-cleansing compliance. Despite these encouraging results, mainly due to the accessibility of these non-aqueous products, three major obstacles remain before a wide acceptance by healthcare workers: distrust in terms of efficacy, distrust in terms of skin tolerance and lack of knowledge on hand-cleansing indications. PMID- 11759029 TI - Disinfectant activity against different morphological forms of Helicobacter pylori: first results. AB - The pathogenic bacterium Helicobacter pylori, which has infected more than one half of the world's human population, exists in two morphological forms; the viable helical form and the disputed viable-but-not-culturable coccoid form. Infection by the helical form proceeds through the oral-oral route, while that by the coccoid form, if possible at all, is by the faecal-oral and/or the oral-oral route. The present pilot study addresses the question of disinfectant efficacy against both forms of the bacterium. PMID- 11759030 TI - Surface disinfection: should we do it? AB - The effective use of disinfectants constitutes an important factor in preventing hospital-acquired infections. Surfaces are considered non-critical items as they come in contact with intact skin. Use of non-critical items or contact with non critical surfaces carries little risk of transmitting a pathogen to patients. Thus, the routine use of disinfectants to disinfect hospital floors and other non critical items is controversial. However, surfaces may potentially contribute to cross-transmission by acquisition of transient hand carriage by health care personnel due to contact with a contaminated surface or by patient contact with contaminated surfaces or medical equipment. This paper reviews the epidemiological and microbiological data regarding the use of disinfectants on non-critical surfaces. It concludes that while non-critical surfaces are uncommonly associated with transmission of infections to patients, one should clean and disinfect surfaces on a regularly scheduled basis. PMID- 11759031 TI - Reprocessing of thermosensitive materials--efficacy against bacterial spores and viruses. AB - To estimate process parameters for non-thermal methods of antimicrobial inactivation, the half-cycle method is very often used. However, the essential premise of this method of estimation, the independence of microbial inactivation kinetics from the microbial load, seems not to be true. Consequently, the attainment of the sterility assurance level as recommended by the pharmacopoeias by a process which has been validated using the half cycle method is not guaranteed. For the evaluation of such chemo-thermo disinfection processes, the quantification of remaining hepatitis B virus DNA (HBV-DNA) traces on the surface of instruments is a useful tool. An infection can be excluded if a decrease of the HBN3-DNA residues on the instruments below the minimum infective dose can be demonstrated. Using the signal amplification technique to detect HBV-DNA on instruments, the safety of an reprocessing procedures can be improved. PMID- 11759032 TI - How to improve instrument disinfection by ultrasound. AB - Ultrasound technologies have a wide range of hospital and dental applications which include cleaning and disinfection of surgical and dental instruments. We measured the germicidal efficacy of sonication, with or without chemical disinfectants, in an ultrasonic bath delivering a frequency of 35 kHz and an intensity of 0.66 W/cm2. Cultures of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans were exposed to ultrasound and to an amine-based disinfectant in non-bactericidal concentrations. Ultrasonication for 60 min alone did not cause a significant killing of the bacteria and yeast. However, we were able to show that sonication can act as a powerful synergistic agent to increase the cidal efficacy of the disinfectant against S. aureus and P. aeruginosa. C. albicans was more resistant to the combination of ultrasound and chemical disinfection. The key role in the action of ultrasound in cleaning of instruments and perhaps in enhanced disinfection is played by cavitation phenomena. The distribution of cavitations in an ultrasonic bath is not homogenous. We found a similar synergistic effect of ultrasound and disinfectant in positions with low cavitation. The synergistic effect was not reduced inside rubber tubes. Before ultrasound can be accepted as an integral part of the cleaning and disinfection process of medical instruments, the influence of intensity and frequency of sonication and the effects of cavitation must be clarified. PMID- 11759033 TI - Manual cleaning and disinfection of flexible endoscopes--an approach to evaluating a combined procedure. AB - Compliance in endoscope reprocessing is unsatisfactory worldwide. The success of the reprocessing procedure relies upon both disinfection and cleaning. Products for instrument disinfection have to be tested accordingly. However, there is still no accepted standard against which to test the result of the cleaning procedure. Different strategies for endoscope reprocessing are possible: one- or two-step procedures. The decision for the method chosen strongly depends on the possibilities in individual hospitals. Products based on glutaraldehyde should not be used if it is not absolutely certain that instruments are already clean. There has to be an awareness that instruments are not designed for easy cleaning. A one-step procedure with products based on aliphatic amines could be an alternative. Methods of assessing such a procedure are suggested. PMID- 11759034 TI - Residuals on medical devices following reprocessing. AB - Micro-organisms may be transmitted by medical devices. A large variety of infectious agents may be involved in infections transmitted by endoscopic procedures. We review a series of examples that demonstrate to what extent micro organisms can be detected on medical devices and how transmission on to subsequently examined persons due to inadequate reprocessing can occur. Hardly any data are available regarding residuals of process chemicals, although numerous published cases of glutaraldehyde-related colitis demonstrate that this issue requires urgent clarification. A risk of endoscope contamination exists, interalia, if washer-disinfectors are technically defective or are incorrectly operated. In particular, a final rinse water of poor microbiological quality can lead to recontamination of endoscopes. PMID- 11759035 TI - MRSA patients: proven methods to treat colonization and infection. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to cause serious nosocomial infections in many hospitals. Measures used to control the spread of these infections include ongoing laboratory-based surveillance, placing colonized and infected patients in isolation, use of barrier precautions and handwashing and hand antisepsis. Culturing hospitalized patients at high risk of acquiring MRSA can facilitate detection and isolation of colonized patients. Eradicating MRSA nasal colonization among affected patients and healthcare personnel has also been as a control measure, with variable success. Eradicating MRSA nasal carriage from epidemiologically-implicated healthcare workers has been used on a number of occasions to control outbreaks. Attempts to eradicate MRSA colonization among affected patients has proven difficult. Of more than 40 different decolonization regimens that have been tested during the last 60 years, topical intranasal application of mupirocin ointment has proven to be the most effective. However, intranasal application of mupirocin has limited effectiveness in eradicating colonization in patients who carry the organism at multiple body sites. Furthermore, because decolonization of patients has virtually always been used in combination with other control measures, its efficacy has been difficult to determine. Because MRSA is transmitted primarily on the hands of healthcare workers, greater emphasis should be given to improving hand hygiene practices among health personnel. For patients infected with MRSA, vancomycin remains a drug of choice. PMID- 11759036 TI - Antibody-producing cells correlated to body weight in juvenile chinook salmon (Oncorhynchus tshawytscha) acclimated to optimal and elevated temperatures. AB - The immune response of juvenile chinook salmon (Oncorhynchus tshawytscha) ranging in weight from approximately 10 to 55 g was compared when the fish were acclimated to either 13 or 21 degrees C. A haemolytic plaque assay was conducted to determine differences in the number of antibody-producing cells (APC) among fish of a similar age but different body weights. Regression analyses revealed significant increases in the number of APC with increasing body weight when fish were acclimated to either water temperature. These results emphasise the importance of standardising fish weight in immunological studies of salmonids before exploring the possible effects of acclimation temperatures. PMID- 11759037 TI - The efficacy of a commercial beta-glucan preparation, EcoActiva, on stimulating respiratory burst activity of head-kidney macrophages from pink snapper (Pagrus auratus), Sparidae. AB - This study investigated the in vitro effects of a commercial beta-glucan preparation, EcoActiva, on the respiratory burst activity of head-kidney macrophages isolated from pink snapper (Pagrus auratus), a marine fish cultured in Australia. Macrophages incubated with EcoActiva displayed morphological characteristics of activation, and were stimulated to produce superoxide. Pre incubation with low levels of EcoActiva significantly increased the response to phorbol myristate acetate (PMA) and lipopolysaccharide (LPS), indicating that EcoActiva could prime these macrophages. Co-culturing macrophages with both LPS and PMA, or EcoActiva and PMA, increased burst activity compared with the response to PMA alone, however, this increase was additive and not synergistic. These results suggest that EcoActiva is able to stimulate non-specific immunity in snapper through increased respiratory burst activity of macrophages, an important component of the host defence network. PMID- 11759038 TI - Immunostimulatory CpG oligodeoxynucleotides stimulate expression of IL-1beta and interferon-like cytokines in rainbow trout macrophages via a chloroquine sensitive mechanism. AB - Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs are known to stimulate immune responses and are potent adjuvants in higher vertebrates, but so far the effects in fish are poorly described. We here report that CpG ODNs induce IL-1beta expression and production of interferon-like cytokines in rainbow trout head-kidney macrophages, whereas ODNs with an inverted motif (GpC) have a much less stimulatory effect. We further demonstrate that endosomal maturation is essential for CpG signalling, as chloroquine, a compound known to block endosomal acidification, inhibits cytokine expression in the macrophages. PMID- 11759039 TI - Effect of dietary beta-1,3 glucan on immune responses and disease resistance of healthy and aflatoxin B1-induced immunocompromised rohu (Labeo rohita Hamilton). AB - The immunostimulant beta-1,3 glucan was fed at 0.1% in feed for 7 days to healthy and aflatoxin B1 (AFB1)-induced immunocompromised fish, Labeo rohita (one of the major tropical carp species), in a 60 day trial. The effects of AFB1, glucan and their interactions on non-specific and specific immunity levels and disease resistance of fish were studied. A single intraperitoneal injection of AFB1 at 1.25 mg kg(-1) body weight) caused a significant (P < 0.05) reduction in non specific immunity as measured through neutrophil phagocytic indices, serum bactericidal activity, and specific immunity as measured through bacterial agglutination titre against Edwardsiella tarda, as well as reduced protection against Aeromonas hydrophila challenge in comparison to control fish which were exposed neither to aflatoxin nor to glucan. Feeding of glucan to healthy fish raised the non-specific and specific immunity level and protection against bacterial infection compared with the control. Feeding of glucan to AFB1-induced immunocompromised fish for 7 days significantly raised the degree of resistance against A. hydrophila challenge and the non-specific immunity level in comparison to non-treated AFB1 exposed fish. Although feeding of glucan was able to increase specific immunity, all measured through haemagglutination titre against sheep red blood cells, and bacterial (E. tarda) agglutination titre in healthy fish in comparison to all other groups, no significant increase in specific immunity to the aflatoxin-exposed group was seen. PMID- 11759040 TI - Rainbow trout (Oncorhynchus mykiss) recombinant IL-1beta and derived peptides induce migration of head-kidney leucocytes in vitro. AB - The present work provides the first information concerning the chemoattractant activity of trout recombinant IL-1beta and its derived peptides, referred to as P1, P2 and P3. The predicted rainbow trout mature interleukin-1beta peptide was produced as a recombinant protein in Escherichia coli. The first peptide, P1, corresponded to fragment 146-157 (YVTPVPIETEAR) of the trout sequence and had an MW of 137 kDa. It was equivalent to a region known to be part of the receptor binding domain from the mammalian crystal structure of IL-1beta complexed to its receptor. P2 was used as control peptide, consisting of the same 12 amino acids as P1, but arranged in a random sequence (VVEEYIRAPPTT). P3 was synthesised to complex with an adjacent region of the IL-1 receptor, and corresponded to fragment 207-216 (YRRNTGVDIS) of the trout sequence, with an MW of 1.18 kDa. Migration was stimulated when leucocytes were exposed to concentrations of > or = 10 ng ml(-1) rIL-1beta. Peptide P3 also induced leucocyte migration, with an optimal dose of 0.25 mM being recorded. While P1 had no effect on cell migration when used alone, synergism was evident as a consequence of combining P1 with a suboptimal dose (0.01 mM) of P3. No synergism occurred when cells were exposed to a combination of P3 and the control peptide P2. PMID- 11759041 TI - Phylogeny of cytokines: molecular cloning and expression analysis of sea bass Dicentrarchus labrax interleukin-1beta. AB - In this paper the cloning of interleukin-1beta (IL-1beta) from the fish Dicentrarchus labrax (sea bass) is described. Using degenerate primers designed from known IL-1beta sequences, a cDNA fragment was amplified by PCR and elongated by 3' and 5' RACE to give the full-length coding sequence for sea bass IL-1beta. The cDNA is 1292 bp, lacks a putative ICE cut site, and codes for a deduced peptide of 29.4 kDa with a pI of 5.1. Sequence analysis showed highest amino acid similarity with rainbow trout (62%), Xenopus (46%), and carp (45.5%) IL-1beta sequences. Expression studies show that sea bass IL-1beta can be upregulated by bacterial lipopolysaccharide both in vitro and in vivo in leucocytes from blood, head-kidney, spleen, gills and liver, whereas the IL-1beta transcript was not detectable in thymus and gut-associated lymphoid tissue. Northern blot analysis with head-kidney leucocyte RNA showed a main LPS-upregulated band at 1.3 kb, and two minor bands at 0.9 and 3.0 kb, respectively. Phylogenetic comparisons with IL 1beta from other vertebrates is presented. PMID- 11759042 TI - Respiratory burst of turbot (Scophthalmus maximus) macrophages in response to experimental infection with viral haemorrhagic septicaemia virus (VHSV). PMID- 11759043 TI - Distribution and identification of red yeasts in deep-sea environments around the northwest Pacific Ocean. AB - We isolated 99 yeast strains, including 40 red yeasts, from benthic animals and sediments collected from the deep-sea floor in various areas in the northwest Pacific Ocean. Comparing the yeast isolates from animals and sediments collected from shallow locations, the proportion of red yeasts differed considerably, comprising 81.5% and 10.6% of the isolates from animals and sediments, respectively. All of the red yeast isolates belonged to the genera Rhodotorula and Sporobolomyces. On the basis of morphological and physiological characteristics, the isolates were identified as R. aurantiaca, R. glutinis, R. minuta and R. mucilaginosa of the genus Rhodotorula, and S. salmonicolor and S. shibatanus of the genus Sporobolomyces. Only R. glutinis and R. mucilaginosa were isolated from sediments. All of the others were isolated from animal sources. Phylogenetic analyses based on internal transcribed spacer (ITS) regions and 5.8S rRNA gene sequences allowed us to establish the precise taxonomic placement of each of the isolates and thereby investigate the intraspecific relationships among the isolates. Twenty-two strains identified as members of R. glutinis, which showed a wide distribution in the deep-sea, and five isolates identified as R. minuta, which were isolated only from benthic animals, showed substantial heterogeneity within the species. The isolates phenotypically identified as Sporobolomyces species and R. mucilaginosa phylogenetically occupied the placements corresponding to these species. Some strains assigned to known species on the basis of phenotypic features should be regarded as new species as suggested by the results of molecular analysis. PMID- 11759044 TI - Production of poly-3-hydroxybutyrate by Bacillus sp. JMa5 cultivated in molasses media. AB - A strain of Bacillus sp. coded JMa5 was isolated from molasses contaminated soil. The strain was able to grow at a temperature as high as 45 degrees C and in 250 g/l molasses although the optimal growth temperature was 35-37 degrees C. Cell density reached 30 g/l 8 h after inoculation in a batch culture with an initial concentration of 210 g/l molasses. Under fed-batch conditions, the cells grew to a dry weight of 70 g/l after 30 h of fermentation. The strain accumulated 25-35%, (w/w) polyhydroxybutyrate (PHB) during fermentation. PHB accumulation was a growth-associated process. Factors that normally promote PHB production include high ratios of carbon to nitrogen, and carbon to phosphorus in growth media. Low dissolved oxygen supply resulted in sporulation, which reduced PHB contents and dry weights of the cells. It seems that sporulation induced by reduced supply of nutrients is the reason that PHB content is generally low in the Bacillus strain. PMID- 11759045 TI - Virulence factors of Escherichia coli isolated from urine of diabetic women with asymptomatic bacteriuria: correlation with clinical characteristics. AB - Since Escherichia coli isolated from compromised patients with symptomatic urinary tract infections (UTIs) express fewer virulence factors than those isolated from healthy controls, the question arises whether this is also the case for diabetic patients with asymptomatic bacteriuria (ASB). Polymerase chain reaction (PCR) assays were conducted on 111E. coli strains, isolated from the urine of diabetic women with ASB, using primers for the major subunit A and the G adhesin (I, II, and III) of P fimbriae, type 1 fimbriae, S fimbriae, afimbrial adhesin, cytotoxic necrotizing factor (CNF), and aerobactin. Phenotypically, hemolysis, mannose-sensitive hemagglutination, mannose-resistant hemagglutination and O:K:H-serotypes were determined. Furthermore, we investigated the associations between virulence factors and patient characteristics (including deterioration of renal function). Type 1 fimbriae were the most prevalent virulence factor (86% by genotyping and 59% phenotypically). Except for a lower prevalence of known uropathogenic O-serotypes, we found the same number of virulence factors in our compromised patient group as listed in the literature in noncompromised patients with ASB. Certain virulence factors (type 1 and S fimbriae and CNF) of the causative E. coli correlated with the risk of a decline in renal function. In conclusion, the number of virulence factors in E. coli isolated from the urine of diabetic women with ASB are comparable with the results found in other (noncompromised) patients with ASB. Furthermore, certain virulence factors of E. coli might contribute to a decline in renal function. PMID- 11759046 TI - Effects of different nutrients on bacterial growth in a pilot distribution system. AB - The growth of bacterial communities in drinking water distribution systems can lead to the development of problems incompatible with water quality requirements. This study was carried out in order to determine which factors promote bacterial growth in distribution networks. A pilot distribution system was used to perform these experiments. After addition of three different inorganic elements to the network (N, P and S) the results obtained show that they did not contribute to the growth or bacteria either in the circulating water or on the surface of the pipes of the distribution system. However, when organic carbon was added an increase in the number of circulating bacteria was observed though the number of bacteria in the biofilms of the network was constant. These results indicate that in the drinking water of the Barcelona distribution system the factor that controls the growth of bacteria is organic carbon. Moreover, bacteria from the biofilm growing on the surface of the pipes may cause the problems of bacterial growth. PMID- 11759047 TI - Vector-free cloning of a bacterial endo-1,4-beta-glucanase in Lactobacillus plantarum and its effect on the acidifying activity in silage: use of recombinant cellulolytic Lactobacillus plantarum as silage inoculant. AB - In this research, the advantage of use of cellulolytic recombinant Lactobacillus plantarum as microbial inoculants for alfalfa silage fermentation was evaluated. To such purpose, two L. plantarum strains, one (L. plantarum Lp80) currently commercialised and the other (L. plantarum B41) suitable as silage microbial additive, were genetically modified by integration of celA gene, encoding an alkaline endo-1,4-beta-glucanase from Bacillus sp., in the chromosome, by means of a vector-free cloning technique. The heterologous gene was cloned in two fashions: preceded by two promoters (AC1 modification) or in translational coupling with a partial upstream ORF (AC2 modification). Therefore two different genetically modified organisms (GMOs) per each wild-type (WT), producing 43-59 U/l cellulase in 16 h, were examined. Thirty-five micro-ensiling experiments were carried out by inoculating the WT or the derived GMOs. L. plantarum B41AC1 cellulolytic clone exhibited significantly increased acidification capacity in silage samples incubated at 37 degrees C. No advantage of use was evident for the other GMOs. PMID- 11759048 TI - Cuniculitrema polymorpha (Tremellales, gen. nov. and sp. nov.), a heterobasidiomycete vectored by bark beetles, which is the teleomorph of Sterigmatosporidium polymorphum. AB - In a study of the mycobiota associated with bark beetles, a dimorphic fungus producing longitudinally septate basidia of the Tremella-type and yeast cells budding off from stalks, was collected. Detailed morphological, physiological and molecular studies revealed that this fungus represents the teleomorph of Sterigmatosporidium polymorphum. Consequently, a new genus, Cuniculitrema gen. nov., and a new species, C. polymorpha sp. nov., are proposed. Comparative morphological and molecular studies indicated that the new taxon belongs to a group that also comprises species of the stalk-forming anamorphic genera Fellomyces and Kockovaella. The new family Cuniculitremaceae is proposed for this group. PMID- 11759049 TI - Pyrimidine base catabolism in Pseudomonas putida biotype B. AB - Reductive catabolism of the pyrimidine bases uracil and thymine was found to occur in Pseudomonas putida biotype B. The pyrimidine reductive catabolic pathway enzymes dihydropyrimidine dehydrogenase, dihydropyrimidinase and N-carbamoyl-beta alanine amidohydrolase activities were detected in this pseudomonad. The initial reductive pathway enzyme dihydropyrimidine dehydrogenase utilized NADH or NADPH as its nicotinamide cofactor. The source of nitrogen in the culture medium influenced the reductive pathway enzyme activities and, in particular, dihydropyrimidinase activity was highly affected by nitrogen source. The reductive pathway enzyme activities in succinate-grown P. putida biotype B cells were induced when uracil served as the nitrogen source. PMID- 11759050 TI - Physiology, biochemistry and taxonomy of deep-sea nitrile metabolising Rhodococcus strains. AB - A collection of nitrile-hydrolysing rhodococci was isolated from sediments sampled from a range of deep coastal, and abyssal and hadal trench sites in the NW Pacific Ocean, as part of our programme on the diversity of marine actinomycetes. Nitrile-hydrolysing strains were obtained by batch enrichments on nitrile substrates with or without dispersion and differential centrifugation pre treatment of sediments, and were recovered from all of the depths sampled (approximately 1100-6500 m). Two isolates obtained from the Ryukyu (5425 m) and Japan (6475 m) Trenches, and identified as strains of Rhodococcus erythropolis, were chosen for detailed study. Both of the deep-sea isolates grew at in situ temperature (4 degrees C), salinities (0-4% NaCl) and pressures (40-60 MPa), results that suggest, but do not prove, that they may be indigenous marine bacteria. However, the absence of culturable Thermoactinomyces points to little or no run off of terrestrial microbiota into these particular trench sediments. Nitrile-hydrolysis by these rhodococci was catalysed by a nitrile hydratase amidase system. The hydratase accommodated aliphatic, aromatic and dinitrile substrates, and enabled growth to occur on a much wider range of nitriles than the only other reported marine nitrile-hydrolysing R. erythropolis which was isolated from coastal sediments. Also unlike the latter strain, the nitrile hydratases of the deep-sea rhodococci were constitutive. The possession of novel growth and enzyme activities on nitriles by these deep-sea R. erythropolis strains recommends their further development as industrial biocatalysts. PMID- 11759051 TI - Cometabolic biosynthesis of copolyesters consisting of 3-hydroxyvalerate and medium-chain-length 3-hydroxyalkanoates by Pseudomonas sp. DSY-82. AB - A newly isolated strain, designated as Pseudomonas sp. DSY-82, synthesized medium chain-length polyhydroxyalkanoate (MCL-PHA) copolyesters when grown on alkanoates from hexanoate to undecanoate as the sole carbon source. When used alone, butyrate and valerate supported the growth of the isolate but not PHA production. However, unusual polyesters containing 3-hydroxyvalerate, as well as various MCL 3-hydroxyalkanoate monomeric units, were synthesized when valerate was cofed with either nonanoate or 10-undecenoate, suggesting the formation of monomer units from both substrates. Concentrations of 3-hydroxyvalerate, 3-hydroxyoctanoate, and 3-hydroxydecanoate in the PHAs produced were significantly elevated by the addition of valerate, indicating that the incorporation of these monomer units to PHA occurred primarily through cometabolism. The total amount of these monomer units in the PHAs reached up to 30%. The PHAs produced in this study were most likely random copolyesters as determined by differential scanning calorimetric analysis. This is the first case of microbial synthesis of copolyesters consisting of 3-hydroxyvalerate and MCL 3-hydroxyalkanoate monomer units through cometabolism. PMID- 11759052 TI - Selection of a potential probiotic Lactobacillus strain and subsequent in vivo studies. AB - The probiotic potential of a Lactobacillus strain, isolated from pig faeces, was assessed as a probiotic in piglets. The strain was examined for resistance to pH 2.0, 0.5% oxgall and antibiotics, and antimicrobial activities against enteric pathogenic bacteria. The probiotic strain, L. reuteri BSA131, was administered through the feed to 25 1-month-old Landrace piglets. The piglets were divided into five groups of five piglets each and fed with different diets for 28 days. The daily consumption of L. reuteri BSA131 was assigned into two groups by the concentration of 10(6) or 10(8) freeze-dried bacteria. Fecal samples were collected before, during, and after consumption. Lactobacilli and enterobacteria cell counts were determined in the fecal samples. The liveweight gains and feed consumption of the piglets were recorded daily. This study showed that strain BSA131 enhanced liveweight gains and feed conversion rates in piglets. It also showed a significant increase in lactobacilli cell counts and decreases in enterobacterial numbers in the fecal samples. Strain BSA131 was considered to be a potential probiotic for piglets, especially after weaning. PMID- 11759053 TI - A new monoclonal anti-CD7 antibody reactive on paraffin sections. AB - CBC.37 monoclonal antibody (mAb) was generated using balb/c mice immunized with CEM T cell line. It was selected because of its strong reactivity on T lymphocytes on paraffin tissue sections. The anti-CD7 specificity of CBC.37 mAb was assessed by immunohistochemistry, cross-blocking, and cross immunoprecipitation experiments using CBC.37 and the anti-CD7 mAb DK24. CBC.37 mAb immunoprecipitated a 40-kDa protein. Cross-blocking and cross immunoprecipitation experiments demonstrated that the two antibodies recognized the same molecule. Immunostaining of a large number of reactive lymph nodes and B and T cell lymphomas confirms that CBC.37 mAb was directed against T cells. As expected, on reactive lymph nodes the staining pattern was comparable to that of CD3. Among the 110 T cell lymphomas examined, all T lymphoblastic lymphomas were positive (15+/15; 100%). As a result of the frequent loss of CD7 antigen, only 25+/95 (26%) of peripheral T cell neoplasms were found to be positive for CBC.37. A marked reduction in the number of CBC.37-positive T cells was observed in 7 of the 60 cases of benign inflammatory dermatoses studied (approximately 12%). CBC.37 was unreactive with all healthy and neoplastic non-lymphoid samples examined. Because the lack of CD7 expression in T cell lymphomas is of diagnostic value, CBC.37 mAb in association with other anti-T cell antibodies working on paraffin sections could be of particular value in asserting the diagnosis of T cell lymphomas in routine histopathology. PMID- 11759054 TI - Cytokeratin immunostaining patterns of benign, reactive lymph nodes: applications for the evaluation of sentinel lymph node specimen. AB - The use and interpretation of cytokeratin (CK) immunostains of sentinel lymph node specimens for breast carcinoma remain controversial. Variable immunoreactivity with anti-CK antibodies and CK-positive interstitial reticulum cells may complicate interpretation. The authors examined a series of reactive lymph nodes selected from patients without a history of malignancy. To demonstrate potential diagnostic pitfalls, three different CK antibody combinations were studied to characterize the immunostaining patterns. Formalin fixed sections of lymph nodes were immunostained with a labeled streptavidin biotin method using a DAKO autostainer. The anti-CK antibody preparations evaluated were AE1/AE3, CAM 5.2, and an in-house-prepared CK cocktail composed of 7 antibodies. The authors observed that up to 10% of cells in benign, reactive lymph nodes may be immunoreactive with anti-CK antibodies. AE1/AE3 stained 2 of 20 cases with rare immunoreactive reticulum cells, whereas CAM 5.2 and the CK cocktail immunostained cells in 85% of cases with reticulum cells in sinuses and the paracortex. Rare positive to 2+ cells were present in a similar distribution with these two antibodies. Careful interpretation of CK immunostaining of sentinel lymph node biopsies is essential, as is awareness of the presence of CK positive native reticulum cells, to avoid confusion with single cells of metastatic carcinoma. PMID- 11759055 TI - Specific but variable expression of h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker. AB - h-Caldesmon is considered a novel specific marker for tumors with smooth muscle differentiation. To reassess its diagnostic use, the authors evaluated the immunohistochemical expression of h-caldesmon and other myogenic markers (calponin, alpha-smooth muscle actin, HHF35, and desmin) in 30 leiomyosarcomas (external soft tissues [15], retroperitoneum [8], uterus [5], other sites [2]), 26 myofibroblastic lesions, and 26 fibrohistiocytic tumors of varying biologic potential and histology. In contrast with previous data, h-caldesmon was expressed only in 11 (36%) of the 30 leiomyosarcomas analyzed, whereas they consistently expressed actins and frequently expressed calponin (86%) and desmin (76%). Leiomyosarcomas with the expression of h-caldesmon were well or moderately differentiated and primarily confined to the retroperitoneum or uterus. All but one leiomyosarcomas in the external soft tissues examined were negative for h caldesmon, and the h-caldesmon-negative tumors showed moderately to poorly differentiated morphology. All myofibroblastic lesions examined were negative for h-caldesmon despite their constant expressions of at least one of the other markers. h-Caldesmon was not expressed in fibrohistiocytic tumors either, although focal positivity for the other markers was seen in subsets of the tumors. Thus, h-caldesmon can be regarded as a specific myogenic marker. However, one should be aware that the expression of h-caldesmon in leiomyosarcomas can be more variable according to their locations and/or extent of smooth muscle differentiation than considered previously. PMID- 11759056 TI - Expression of CD44S and CD44v5 is more common in stage III than in stage I serous ovarian carcinomas. AB - Experimental evidence suggests that attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44 on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. The authors therefore evaluated local and disseminated ovarian serous carcinomas for the expression of standard CD44 and CD44 splice variants CD44v5, CD44v6, and CD44v7/8. The relative amount of hyaluronic acid (HA) in stroma surrounding tumor nests also was studied. Using immunohistochemistry and archival tissue, 14 serous ovarian carcinomas confined to the ovary (stage I) and 14 serous ovarian carcinomas with peritoneal implants and positive peritoneal fluid (stage III) were stained with antibodies to standard CD44, CD44v5, CD44v6, and CD44v7/8. All tissues also were analyzed for HA using a HA binding peptide. Immunostaining was classified as focal or diffuse and graded from 1 to 4 based on intensity. Immunoreactivity for standard CD44 was seen in 5 of 14 (36%) stage I tumors and 10 of 14 (71%) stage III tumors. Similarly, immunoreactivity with CD44v5 was seen in 2 of 14 (14%) stage I tumors and 9 of 14 stage III tumors (64%). Hyaluronic acid was present in the stroma surrounding all stage I and III tumors, but was more intense in the stroma adjacent to metastatic implants from stage III carcinomas. Tumor cells were uniformly negative for intracellular HA. These results suggest that CD44S and CD44v5 are differentially expressed in early (stage I) and advanced (stage III) ovarian serous carcinomas and support previous studies that suggest a role for CD44 and stromal HA in the dissemination of ovarian epithelial cancer. PMID- 11759057 TI - Paxillin: application of immunohistochemistry to the diagnosis of chromophobe renal cell carcinoma and oncocytoma. AB - Paxillin is a cytoskeletal protein that was recently identified as a component of focal adhesions and links between F-actin and integrin. In this study, 91 renal tumors--65 conventional renal cell carcinomas (RCCs), 14 papillary RCCs, 6 chromophobe RCCs, 4 collecting duct carcinomas, 2 oncocytomas--were investigated for the immunohistochemical expression of paxillin. In a normal kidney, paxillin was predominantly expressed in the cytoplasm of distal tubules, loops of Henle, collecting ducts, and vascular smooth muscle cells. In all of the chromophobe RCCs and oncocytomas, strong expression of paxillin was observed in the tumor cytoplasm. In contrast to these tumors, conventional RCCs, papillary RCCs, and collecting duct carcinomas showed negative reactions for paxillin except for one case in each subgroup with weak reactivity. An immunoblot analysis confirmed the presence of paxillin in healthy kidney, chromophobe RCC, and oncocytoma. These data suggest that paxillin possibly plays a role in signal transductions as a focal adhesion intervening between tumor cells and the extracellular matrix in renal tumors with collecting duct phenotypes such as chromophobe RCCs and oncocytomas, but not in conventional RCCs. In addition, paxillin may be an available marker in distinguishing chromophobe RCCs from conventional or papillary RCCs. PMID- 11759058 TI - Immunohistochemical detection of fibroblast growth factor receptors in normal endocrine cells and related tumors of the digestive system. AB - Endocrine tumors (ETs) of the digestive system produce several growth factors including acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), which are thought to be involved in the growth of tumor cells and in the proliferation of tumor stromal cells. Their actions depend on binding to four specific receptors--FGFR1, FGFR2, FGFR3, and FGFR4--whose distribution in normal endocrine cells and related tumors of the gastroenteropancreatic (GEP) system has previously been examined. Formalin-fixed, paraffin-embedded normal tissues and 60 well-characterized GEP endocrine tumors were immunostained using specific antibodies directed against various GEP hormones, aFGF, FGFR1, FGFR2, FGFR3, and FGFR4. Acidic FGF immunoreactivity (IR) was found in gut EC cells; FGFR1 immunoreactivity in rare duodenal endocrine cells and in pancreatic A cells; FGFR2 immunoreactivity in gastric and duodenal G cells, pancreatic B cells, and rectal EC cells; FGFR3 immunoreactivity in duodenal G cells; and FGFR4 immunoreactivity in rectal L cells and in pancreatic B, PP, and A cells. Immunoreactivity for at least one of the four FGFRs was found in all tumors, independently of FGFR expression in the putative cell of origin. EC cell tumors, which were all positive for aFGF, were found to express at least three different FGFRs. FGFRs also were localized in the stromal cells of all the tumors examined. The tumor stroma was more abundant in EC cell tumors than in other types of neoplasms. The results suggest that aFGF-FGFR interaction may be involved in the modulation of normal endocrine cell functions and in the regulation of tumor growth and stromal proliferation of EC cell carcinoids. PMID- 11759059 TI - bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with rectal cancer. AB - Combined radiation therapy and chemotherapy are adjuvant treatments given after surgery to patients with rectal carcinoma. Because apoptosis seems to play a role in tumor response to radiotherapy, the current study investigates whether there is a correlation between the ratio of bcl-2 oncoprotein and bax expression in rectal adenocarcinoma and the clinical response to radiotherapy. Elective colectomy for primary rectal adenocarcinoma followed by adjuvant radiotherapy and chemotherapy was performed on 35 patients. Tumors were staged as B2 (n = 30) and C (n = 5), and were classified as radiation resistant (n = 19, group A) and radiation nonresistant (n = 16, group B). Immunohistochemical study, using the streptavidin-biotin complex technique and monoclonal antibody to bcl-2 and polyclonal antibody to bax protein was used on paraffin sections. Cases were considered positive if at least 5% of tumor cells displayed cytoplasmic staining for bcl-2 or bax. In each tumor, the bcl-2/bax ratio was calculated dividing the percentage of bcl-2-positive cells by the percentage of bax-positive cells. For statistical analysis, the Mann-Whitney rank sum test and Kruskal-Wallis analysis of variance test were used. Rectal tumors of group A displayed significantly greater bcl-2 immunoreactivity (40.2 +/- 4.2) compared with group B (20.2 +/- 3.8). In contrast, expression of bax protein was less in group A (30.3 +/- 3.3) compared with group B (41.3 +/- 2.3). The bcl-2/bax ratio was greater in group A (1.3 +/- 0.1) compared with group B (0.49 +/- 0.1), and was correlated with poor responsiveness to radiotherapy. The current study indicates that in patients with rectal carcinoma an elevated bcl-2/bax ratio in tissue specimens suggests increased tumor resistance to adjuvant radiotherapy. Thus, in such patients, the bcl-2/bax ratio may serve as a potential molecular marker for prediction of tumor prognosis. PMID- 11759060 TI - Light and electron microscopy of the pagetoid spread of germ cell carcinoma in the rete testis: morphologic evidence suggestive of field effect as a mechanism of tumor spread. AB - The purpose of this study is to investigate the mechanism of tumor spread in the pagetoid spread of germ cell tumors in the rete testis (PSRT). Twenty consecutive cases of germ cell tumor of the testis (9 seminomas, 3 embryonal carcinomas, and 8 teratocarcinomas) were retrieved to identify the cases with PSRT. The areas of pagetoid spread were examined by the serial sectioning of the entire thickness of the tissue block. Available fresh tissue was submitted for electron microscopic study. Ten cases were associated with PSRT and had focal or extensive areas of intratubular germ cell neoplasia (IGCN) in the proximity of the tumor and the rete testis (RT). In the remaining 10 cases, 6 were associated with IGCN distant from the RT and the last 4 were not associated with IGCN. Seminiferous tubules with IGCN were seen connecting with the RT with pagetoid spread. Isolated single intraepithelial tumor cells also were identified at the periphery of the areas with PSRT. Electron microscopic study of the RT of 4 cases with PSRT (2 seminomas, 1 embryonal carcinoma, and 1 teratocarcinoma) revealed desmosome-type junctions between tumor cells with RT epithelial cells. Direct tumor expansion and cell motility as mechanisms of tumor spread in PSRT does not explain the presence of isolated cells and desmosome-type junctions of the tumor cells as demonstrated in this study. The authors believe that the field effect plays an important part in the pathogenesis of this pagetoid spread in the RT. It is likely that this field effect is induced by the germ cell tumor and is operated through the immature germ cells or undifferentiated epithelial cells in the RT adjacent to the tumor cells. PMID- 11759061 TI - Allelic losses at 3p and 11p are detected in both epithelial and stromal components of cervical small-cell neuroendocrine carcinoma. AB - Microdissected epithelial and stromal cells from 15 cervical small-cell carcinoma patients and 9 healthy control subjects were assessed for loss of heterozygosity with polymorphic DNA markers at chromosomes 3p and 11p. Among malignant lesions assessed with 7 markers at 3p, 21 allelic losses were detected from 193 informative samples. Of losses, 20 were in epithelial and 1 was in normal appearing stromal cells. Among losses in epithelial cells, 16 were from 44 samples informative for 3 markers within 3p21.2-p14.2 (0.36 loss/sample), whereas only 4 were from 54 samples informative for 4 markers outside the region (0.09 loss/sample), suggesting a "hot spot" of genetic alterations within 3p21.2-p14.2. Among malignant lesions assessed with 2 markers within 11p14-p12, 15 losses were seen in 52 informative samples. Of losses, 10 were in epithelial and 5 were in normal-appearing stromal cells. Of 10 epithelial samples showing losses within 11p14-p12, 8 also displayed losses within 3p21.2-p14.2, suggesting a concurrent involvement of these loci in tumor development or progression. The five losses in stromal cells were in four cases that showed no loss in epithelial cells with same markers, suggesting that stromal cells might play initiative roles in tumor development. PMID- 11759062 TI - Effects of acetone, methanol, or paraformaldehyde on cellular structure, visualized by reflection contrast microscopy and transmission and scanning electron microscopy. AB - The authors recently showed variable subcellular immunoreactivity of the Bcl-2 and Bax proteins after fixation of cell monolayers with acetone, methanol, or paraformaldehyde (PF) followed by methanol (PF/methanol). Here, the authors demonstrate by reflection contrast microscopy and transmission electron microscopy that acetone or methanol fixation result in complete loss of integrity of intracellular structures in contrast with PF or glutaraldehyde fixation. Scanning electron microscopy revealed poor preservation of plasma membrane integrity after fixation in acetone or methanol. Fixation with PF before methanol reduced damage to intracellular and plasma membranes. In addition, Western blot analysis demonstrated loss of Bcl-2 and Bax protein during acetone or methanol fixation, whereas PF fixation before methanol permeabilization markedly reduced this loss. For studies on the intracellular localization of soluble or unknown types of antigen, the authors discourage the use of acetone and methanol as single fixatives. PMID- 11759063 TI - A reliable method of demonstrating HER-2/neu, estrogen receptors, and progesterone receptors on routinely processed cytologic material. AB - Estrogen (ER) and progesterone receptors (PR) and HER-2/neu (c-erbB-2) protein overexpression are important prognostic factors for breast carcinoma. This study describes a simple, rapid method that demonstrates the applicability of these tests to cytology smears. Smears were made from scrape samples of fresh breast tumors and were fixed in 95% alcohol for immunohistochemical staining for ER and PR and HER-2/neu protein overexpression. Scraped material was suspended in phosphate-buffered saline, and cytospin slides were prepared from the suspension and air dried for fluorescence in situ hybridization (FISH). The results for ER performed on cytology compared with the gold standard (immunohistochemistry on histology) showed 94% accuracy (95% confidence bounds (0.8432 0.9823)); PR results showed 71% accuracy (95% confidence bounds (0.5805 0.8180)) and HER-2/neu results showed 77% accuracy (95% confidence bounds (0.6500 0.8709)). Using HER 2/neu gene overamplification detected by FISH as the gold standard, immunohistochemistry for HER-2/neu protein overexpression showed sensitivity, specificity, and a positive predictive value of 88.8%, 77.7%, and 80% for histology, respectively, and 69%, 87%, and 90% for cytology, respectively. This study showed that fixation and storage of smears in 95% alcohol were effective for receptor studies, whereas air-dried cytospin smears were well suited to FISH. PMID- 11759064 TI - Tissue microarray technique in soft tissue sarcoma: immunohistochemical Ki-67 expression in malignant fibrous histiocytoma. AB - Malignant fibrous histiocytoma (MFH) represents a heterogeneous soft tissue sarcoma entity. The authors compared different methods to determine immunohistochemical staining in whole tissue sections, evaluated the tissue microarray technique, and assessed immunohistochemical heterogeneity using the proliferation marker Ki-67 in 47 histopathologic tumor blocks from 11 MFHs. Whole tissue sections were assessed counting 400 cells along a line and counting all cells in 10 high-power fields (0.16 mm2) with mean Ki-67 expression levels of 13% and 11%, respectively. For the tissue microarray technique, two to three 0.6-mm diameter biopsies were studied from each of the 47 tumor blocks. Good correlation was obtained between whole tissue immunohistochemistry and tissue microarray with the microarray method, giving on average 8.6% greater Ki-67 expression levels than the reference method. Immunohistochemical tumor heterogeneity, evaluated using the high-power field method, showed a median standard deviation of 2.3% within the tumor blocks and 2.5% between the blocks from the same tumor. The authors concluded that the tissue microarray technique yields good quality staining and expression levels for Ki-67 comparable with whole tissue methods in MFH, but because of tumor heterogeneity, several tumor blocks ideally should be studied and, because of loss of material in the microarray process, multiple biopsies should be taken. The feasibility of tissue microarray for immunohistochemical studies of soft tissue sarcomas offers new possibilities to study multiple markers in large tumor materials. PMID- 11759065 TI - Three-dimensional imaging of hormone-secreting cells and their microvessel environment in estrogen-induced prolactinoma of the rat pituitary gland by confocal laser scanning microscopy. AB - This study focused on the three-dimensional imaging of hormone-secreting cells and their microvascular environment in estrogen-induced prolactinoma of the rat pituitary gland. Adult female Wistar-Imamichi rats were injected with estradiol dipropionate and killed 7 weeks later. Some rats given estrogen for 7 weeks also were injected with bromocriptine before killing. To obtain a detailed three dimensional image of microvessels, dialyzed fluorescein isothiocyanate (FITC) conjugated gelatin was injected into the left ventricle of the rat heart. After the perfusion, the pituitary glands were resected and subjected to immunohistochemistry (IHC). To evaluate the effects of estrogen and bromocriptine, IHC was performed with antibodies against prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH). With the combination, microvessels and cells containing PRL, ACTH, and GH could be clearly identified by confocal laser scanning microscopy (CLSM). The PRL cells increased in number and became hypertrophic after prolonged exposure to estrogen. With bromocriptine administration after estrogen treatment, however, PRL cells decreased in number and became atrophic. The current study revealed that estrogen and bromocriptine had significant effects on PRL secretion and the microvascular environment. Therefore, this technique (FITC injection and IHC) with CLSM is suitable for the three-dimensional imaging of hormone-secreting mechanisms under various conditions. PMID- 11759066 TI - Tracking the assembly pathway of human immunodeficiency virus type 1 Gag deletion mutants by immunogold labeling. AB - The Pr55gag gene product of human immunodeficiency virus type 1 (HIV-1) is sufficient to direct the formation of retrovirus-like particles (RVLPs). Recent biochemical evidence has indicated the presence of Gag intermediates in the cytoplasm; however, the Gag assembly process into RVLPs remains incompletely defined. The authors present here the subcellular localization of Gag mutant proteins in BSC40 and Jurkat cells by immunoelectron microscopy (IEM). The full Gag/Pol and Gag precursors, a C-terminal deletion mutant lacking a portion of nucleocapsid (NC), and all p6Gag gave rise to similar levels of RVLPs at the cell surface. A C-terminal deletion of all NC and p6Gag abrogated particle formation, whereas p24 was found in patches at the cell surface. Deletion of matrix (MA) sequences from Gag resulted in intracellular particles, and myristylation was not required for particle formation in the context of the MA deletion. Matrix expression was enhanced with Gag/Pol or Env coexpression as determined by semiquantitative IEM. p24 protein was targeted at vacuolar and mitochondrial membranes, but not at Golgi cisternae. In addition, aggregations of Gag intermediates and RVLPs in the cytoplasm, rough endoplasmic reticulum, cisternae, and mitochondria were noted. These results provide defined in situ evidence that HIV-1 particle assembly occurs in the cytosol in addition to budding at most intracellular membranes. PMID- 11759067 TI - Tumor-induced immune dysfunctions caused by myeloid suppressor cells. AB - In the late 1970s, several findings suggested that accessory cells distinct from lymphocytes might suppress immune reactivity in tumor-bearing hosts. Studies in animal models and patients later confirmed that cells driven to act as dominant immune suppressors by growing cancers could subvert the immune system. These cells have also been termed natural suppressors, a functional definition connoting their ability to hamper various T- and B-lymphocyte responses without prior activation and independently from antigen and MHC restriction. These properties were attributed to distinct cell populations. The phenotypic discrepancies, together with the lack of antigen specificity, have generated serious restraints to research on tumor-induced suppression. Recent evidence indicates that suppressor cells are closely related to immature myeloid precursors and can be found in several situations that can exert adverse effects on the immunotherapy of cancer. The present review is an attempt to address the nature and properties of immature myeloid suppressors and their relationship to dendritic cells and macrophages, with the aim of clarifying the complex network of tumor-induced, negative regulators of the immune system. PMID- 11759068 TI - Laser scanning cytometry evaluation of MART-1, gp100, and HLA-A2 expression in melanoma metastases. AB - Assessment of antigen expression by solid tumors has relied predominantly on immunohistochemistry, flow cytometry, and more recently quantitative real-time polymerase chain reaction. However, all these techniques present intrinsic limits. The laser scanning cytometer, by combining the properties of light and fluorescence microscopy with those of laser cytometry, can quantitatively and objectively analyze hypocellular samples such as fine-needle aspirates on an individual cell basis. To validate the fidelity of laser scanning cytometry for quantitative immunophenotyping of fine-needle aspirates, the authors measured the expression of the melanoma-associated antigens MART-1 and gp100 as well as HLA A2, a HLA class 1 restriction element associated with their recognition by melanoma-specific T cells. Expression of melanoma antigens and HLA was measured by laser scanning cytometry and immunohistochemistry in fine-needle aspirates from melanoma metastases. In addition, transcription levels of both melanoma antigens were recorded by quantitative real-time polymerase chain reaction. A quantity of less than 1,000 cells per sample (average 682 cells) was sufficient for the analysis. Laser scanning cytometry estimates correlated with those of immunohistochemistry and quantitative real-time polymerase chain reaction for MART-1 and gp100. A good correlation in HLA-A2 detection by laser scanning cytometry and immunohistochemistry was also observed. Moreover, the laser scanning cytometer could discriminate subsets of cells from the same lesion with heterogeneous melanoma antigen expression, leading to the observation that cells with a DNA index greater than 2.5 expressed significantly less gp100. Thus, laser scanning cytometry yields detailed information on protein expression in individual cells and represents a new tool for dissecting the immune response in the tumor microenvironment. PMID- 11759069 TI - Actinomycin D and gemcitabine synergistically sensitize androgen-independent prostate cancer cells to Apo2L/TRAIL-mediated apoptosis. AB - The cytotoxic efficacy and kinetics involved in sensitization of Apo2L/TRAIL resistant, androgen-independent prostate cancer cells to Apo2L/TRAIL or tumor necrosis factor-alpha or Fas ligand-mediated apoptosis were tested using subclinical concentrations of actinomycin D, paclitaxel, cisplatinum, gemcitabine, and radiation in CL-1, LNCaP, DU-145, and PC3 prostate cancer cell lines. CL-1 cells expressed all four Apo2L/TRAIL receptors and were resistant to Apo2L/TRAIL-mediated apoptosis (1-5,000 ng/mL) and to the sensitizers when given alone. Pretreatment with actinomycin D followed by Apo2L/TRAIL or tumor necrosis factor-alpha or anti-Fas CH-11 monoclonal antibody, but not in the reverse order, induced apoptosis in all cell lines. Synergistic sensitization in CL-1 cells was shown also with gemcitabine but not with cisplatinum, VP-16, paclitaxel, or radiation. Incubating the Apo2L/TRAIL-resistant CL-1, LNCaP, DU-145, and PC3 cell lines with 100 ng/mL actinomycin D for 4 hours followed by Apo2L/TRAIL for 24 hours resulted in 45.4 +/- 10.3%, 58.8 +/- 3.6%, 53.4 +/- 1.4%, and 84.2 +/- 8.4% apoptosis, respectively. Prolonging the sensitization time to 24 hours followed by 20 hours of incubation with Apo2L/TRAIL further enhanced the killing activity against CL-1 cells to 89 +/- 1% (delta = 60%, synergistic ratio = 3.1). This killing has a biphasic pattern that was contributed to by apoptosis (83%) and necrosis (17%) at 10 hours (peak) and 40% and 60%, respectively, at 20 hours. These results suggest that prostate cancer cells' resistance to Apo2L/TRAIL mediated apoptosis can be reversed and synergy is achieved by sensitization of tumor cells with subclinical concentrations of actinomycin D or gemcitabine and may be useful clinically for the treatment of metastatic hormone- and drug refractory prostate cancer. PMID- 11759070 TI - Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin. AB - The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment. PMID- 11759071 TI - Generation of chronic myelogenous leukemia-specific T cells in cytokine-modified autologous mixed lymphocyte/tumor cell cultures. AB - Chronic myelogenous leukemia (CML) may be amenable to cell-based adoptive immunotherapy, as suggested by the graft-versus-leukemia effect of bone marrow transplantation and the therapeutic benefit of donor leukocyte infusions. Specific adoptive immunotherapy without bone marrow transplantation might be more effective and less cost-intensive. Professional antigen-presenting cells, the dendritic cells, from patients with CML are derived from the malignant clone and may stimulate antileukemia T-cell responses. Autologous T cells may also be able to recognize tumor antigens on CML cells directly. Here, the authors show that CD4 and CD8 T-cell responses to autologous CML cells can be generated in vitro rapidly and effectively by performing modified autologous mixed lymphocyte/tumor cell cultures (MLTC) in serum-free medium in the presence of cytokines known to support dendritic cell differentiation. MLTC-sensitized T cells secreted large amounts of the type 1 cytokine interferon-gamma, as well as interleukin (IL)-2. However, they also secreted a variety of other cytokines, including the type 2 subtype cytokine IL-13 but not the classic type 2 cytokines IL-4, IL-5, and IL 10. Monoclonal populations of CML-specific CD4 cells could be derived from these lines in limited numbers but showed markedly enhanced reactivity. This suggests that CML-specific T cells are relatively rare in these autologous MTLC-derived sensitized populations, but that their isolation and propagation would yield much more potent antitumor effector cells for use in adoptive immunotherapy without the need for bone marrow transplantation. PMID- 11759072 TI - Antitumor reactivity of lymph node cells primed in vivo with dendritic cell-based vaccines. AB - Tumor lysate-pulsed dendritic cells were used to generate nodal effector T cells in the murine MCA 205 tumor model. Dendritic cells were derived from bone marrow and cultured in granulocyte-macrophage colony-stimulating factor/interleukin 4 before pulsation with tumor lysate. Multiple subcutaneous administrations of tumor lysate-pulsed dendritic cells (TP-DCs) resulted in an approximately eightfold hypertrophy of the vaccine draining nodes, with an increased influx of dendritic (CD11c+/CD80+) cells and B (B220+) cells. The vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3/interleukin 2 and exhibited specific interferon-gamma release to tumor antigen. The adoptive transfer of TP DC VPLN cells resulted in regression of established 3-day pulmonary metastases. The antitumor reactivity of TP-DC VPLN cells was comparable to anti CD3/interleukin 2 activated tumor-draining lymph node cells. However, the admixture of keyhole limpet hemocyanin (KLH) with tumor lysate during pulsation of dendritic cells significantly enhanced the induction of tumor-reactive VPLN cells. Tumor lysate-pulsed dendritic cells can be used as a strategy to generate effector T cells for adoptive immunotherapy. PMID- 11759073 TI - Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations. AB - Dendritic cells (DCs) are major antigen-presenting cells. They are capable of capturing and processing tumor antigens, expressing lymphocyte costimulatory molecules, and secreting cytokines to initiate immune responses. Here, the authors tested the effect of cytokine-induced killer (CIK) cells, a population that includes CD3+CD56+ cells (natural killer T cells), with regard to their capacity to immunomodulate DCs. Cytokine-induced killer cells were cocultured with autologous DCs generated from peripheral blood mononuclear cells. Expression of markers typical for both populations was measured using flow cytometry, and secretion of interleukin (IL)-12 was determined using enzyme-linked immunosorbent assays. Cytotoxicity assays were performed to investigate the role of IL-12 and the importance of cell-cell interactions. Considering this, receptors for IL-12 and CD40 were blocked and cocultures were performed with cell culture inserts. Coculture of CIK cells led to a significant increase of DC-specific, costimulatory, and antigen-presenting molecules in DC cultures. In addition, coculture resulted in a dramatically increase of IL-12 secretion by DCs and to a significant increase in cytotoxic activity of CIK cells toward carcinoma cells. Blockage of IL-12 uptake decreased the cytolytic activity of CIK cells. Cytokine secretion was shown to be important for activation of CIK cells, and also cellular interactions between DCs and effector cells caused a higher cytolytic capacity. Interactions between DCs and CIK cells caused changes in the surface molecule expression of both populations, led to an increase of IL-12 secretion, and rendered an improved cytotoxic activity. The natural killer T cell subpopulation seems to be responsible for this effect. Therefore, coculture of DCs with CIK cells may have a major impact on immunotherapeutic protocols for patients with cancer. PMID- 11759074 TI - Phase I trial of anti-B4-blocked ricin in pediatric patients with leukemia and lymphoma. AB - Monoclonal antibodies, specific for antigens expressed on lymphoid malignancies, which have been conjugated to toxins such as ricin, hold promise in the therapy of childhood leukemia and lymphoma. Anti-B4-blocked ricin (anti-B4-bR) is such an agent, and a phase I study of this agent was conducted in children with relapsed or refractory B-lineage leukemia and lymphoma. Anti-B4-bR was given as two 7-day continuous infusions separated by 7 days. Twenty patients were enrolled and 19 received the drug. Two dosage levels (30 and 40 microg/kg per day) were evaluated. Forty micrograms per kilogram per day was the maximally tolerated dose. Dose-limiting toxicity was capillary leak syndrome. Grade 3 reversible elevation in transaminases was also encountered. Human antimouse antibodies or human antiricin antibodies were detected in five patients. No complete remissions or partial remissions were seen. PMID- 11759075 TI - Resources in the war against bioterrorism. PMID- 11759076 TI - Rectus sheath hematoma as a cause of acute abdominal pain. PMID- 11759077 TI - Surgery for chronic aortic regurgitation: when should it be considered? AB - Deciding when to operate on a patient with chronic aortic regurgitation may be extremely difficult. The timing of surgery requires consideration of the etiology and pathophysiology of the aortic regurgitation, because aortic valve replacement carries morbidity and mortality that must be weighed against the potential problems of continued medical management. Guidelines for the use of surgery in patients with valvular disease have been developed by a joint task force of the American College of Cardiology and the American Heart Association. Practical recommendations based on these guidelines are presented. PMID- 11759078 TI - Treatment of hypothyroidism. AB - Thyroid disease affects up to 0.5 percent of the population of the United States. Its prevalence is higher in women and the elderly. The management of hypothyroidism focuses on ensuring that patients receive appropriate thyroid hormone replacement therapy and monitoring their response. Hormone replacement should be initiated in a low dosage, especially in the elderly and in patients prone to cardiac problems. The dosage should be increased gradually, and laboratory values should be monitored six to eight weeks after any dosage change. Once a stable dosage is achieved, annual monitoring of the thyroid-stimulating hormone (TSH) level is probably unnecessary, except in older patients. After full replacement of thyroxine (T4) using levothyroxine, the addition of triiodothyronine (T3) in a low dosage may be beneficial in some patients who continue to have mood or memory problems. The management of patients with subclinical hypothyroidism (a high TSH in the presence of normal free T4 and T3 levels) remains controversial. In these patients, physicians should weigh the benefits of replacement (e.g., improved cardiac function) against problems that can accompany the excessive use of levothyroxine (e.g., osteoporosis). PMID- 11759079 TI - Gynecologic aspects of Crohn's disease. AB - Because Crohn's disease has a tendency to be transmural and to form fistulas, it may involve contiguous organs. Gynecologic involvement is frequent, diverse and often difficult to diagnose. Inflammation involving adjacent structures has been reported in as many as one third of patients. Enteric fistulas to the vagina, uterus, ovaries, perineum and vulva also have been reported. Diagnosis may not be obvious if pelvic involvement precedes active bowel disease, or if drainage is clear or mucoid. Abscesses, draining sinuses, edema and ulceration of the perineum or vulva are common, and are caused by direct extension from the involved bowel or by granulomas separated from the bowel by normal tissue. Lesions presenting with vulvar hypertrophy, a fluctuant mass or ulceration are easily misdiagnosed. Menstrual abnormalities are reported in more than one half of patients. Pelvic manifestations of Crohn's disease can be psychologically crippling. Patients or physicians may be hesitant to address serious psychosocial morbidity. To optimize management, physicians must be aware of the diverse manifestations, confusing presentations and psychologic morbidity of Crohn's disease. PMID- 11759080 TI - Preventive strategies in chronic liver disease: part II. Cirrhosis. AB - Cirrhosis is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. The modified Child Pugh score, which ranks the severity of cirrhosis based on signs and liver function test results, has been shown to predict survival. Strategies have been established to prevent complications in patients with cirrhosis. Esophageal varices can be identified by endoscopy; if large varices are present, prophylactic nonselective beta blocker therapy should be administered. Alpha fetoprotein testing and ultrasonography can be effective in screening for hepatocellular carcinoma. Vaccines should be administered to prevent secondary infections. The use of nonsteroidal anti-inflammatory drugs should be avoided, and patients should maintain a balanced diet containing 1 to 1.5 g of protein per kg per day. An extensive assessment should be performed before patients with cirrhosis undergo elective surgery. Before advanced liver decompensation occurs, patients should be referred for liver transplantation evaluation. If advanced cirrhosis is present and transplantation is not feasible, survival is between one and two years. PMID- 11759081 TI - CDC issues guidelines on illnesses associated with intentional release of biologic agents. PMID- 11759082 TI - Molecular characterization of the pneumococcal teichoic acid phosphorylcholine esterase. AB - A search to identify proteins with high affinity for choline-containing pneumococcal cell walls (choline-binding proteins) has permitted the localization, cloning, sequencing, and overexpression of a gene (pce), coding for a protein (Pce) that liberates phosphorylcholine from purified cell walls of Streptococcus pneumoniae. The pce gene of the pneumococcal strain R6 encodes a protein of 627 amino acids with a predicted Mr of 72,104. Pce can remove a maximum of 20% phosphorylcholine residues from the cell wall teichoic acid. In silico analysis of Pce shows a modular organization of the enzyme where the choline-binding domain, involved in cell wall substrate recognition, and the catalytic domain are located at the carboxy- and amino-terminal moieties of the protein, respectively. Remarkably, a long tail of 85 amino acids follows the carboxy-terminal domain, a structural feature that had not been described for the published choline-binding proteins. The carboxy-terminal moiety of Pce is assembled by 10 repeated motifs, and the protein has also a cleavable signal peptide of 25 amino acids that renders after its cleavage a mature protein of 69,426 Da (602 amino acids). The pce gene has been expressed in Escherichia coli, and Pce was active when assayed on pneumococcal walls. We have also found that the signal peptide of Pce was functional in E. coli. Biochemical analysis suggested that Pce is the teichoic acid phosphorylcholine esterase of S. pneumoniae that had been biochemically characterized previously. Construction of two pce pneumococcal mutants (R6D and M31D) by insertion-duplication mutagenesis revealed that these mutants grew at a doubling-time similar to those of the parental strains of the wild-type R6 and the lytA-mutant M31, respectively. R6D and M31D were morphologically indistinguishable from the parental strains when whole-mounted cells were observed under the electron microscope and exhibited levels of competence for genetic transformation slightly lower than those reported for R6 and M31. PMID- 11759083 TI - New mutations in pncA of in vitro selected pyrazinamide-resistant strains of Mycobacterium tuberculosis. AB - Mutations within the pncA gene can cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. To study further the mutational events leading to PZA resistance, a H37Rv PZA-susceptible strain was used to derive PZA-resistant mutants in vitro. This parental strain was grown at gradually increased concentrations of PZA (from 200 up to 500 microg/ml). A total of eight variant strains were selected for further study. PZA resistance was selected at 250 microg/ml or higher. Seven of them lost PZase activity and hence were PZA resistant. The remaining strain has shown a functional PZase and hence was sensitive to PZA after being exposed to 200 microg/ml PZA. Sequence analysis shows different novel mutations within the pncA gene of these variants. Two silent mutations at nucleotide 6 (G --> A) and 300 (C --> T) were found in the PZA-sensitive variant. Among the seven PZA-resistant variants, there were three deletion mutations found at nucleotide 78 (G), 79 (A), and 143 (A), all resulting in a frameshift, and one nonsense mutation at nucleotide 102 (C --> G), creating a stop codon TAG. It was observed that the mutations found in the pncA gene of these PZA-resistant mutants show a distinctive pattern: mutation positions moved toward the beginning of the open reading frame correlating with the increase in PZA concentration, suggesting a possible relationship between the increase of PZA concentration and the early occurrence of mutations on the pncA gene. PMID- 11759084 TI - Epidemiology of the genetic elements responsible for acquired glycopeptide resistance in enterococci. AB - Five genotypes of acquired glycopeptide resistance have been documented in enterococci, with vanA and vanB being the most globally widespread and prevalent. Resistance results from the production of peptidoglycan precursors with reduced binding affinity for glycopeptides and is encoded by complex clusters of van genes. The prototype VanA element is Tn1546, a 10.8-kb transposon that carries the vanRSHAXYZ genes. Diverse VanA elements exist, but all share the vanRSHAX cluster and are believed to be derived from a Tn1546 progenitor. The sequences of these genes are remarkably conserved, with only a few point mutations identified. VanA elements do however vary by the presence of deletions and insertion sequences (IS) in nonessential genes (orf1, orf2, vanY, and vanZ) and intergenic regions. IS transposition probably plays a key role in VanA element evolution. By contrast, vanB gene clusters show greater sequence divergence. Three vanB alleles have been reported, of which vanB2 appears to be the most widespread, generally as part of Tn5382 and related elements. To date, only four Enterococcus faecium strains with VanD resistance have been reported, and each contained a distinct vanD allele. The VanE and VanG types have each been identified in single strains of Enterococcus faecalis. The existence of distinct genotypes, together with the allelic nature of vanB and vanD, suggests that van clusters have transferred to enterococci on multiple occasions from undefined donor species, with subsequent horizontal dissemination, particularly of VanA and VanB elements, among enterococci. Characterization of glycopeptide resistance elements yields information on their evolution and broadens our insights into the epidemiology of resistant enterococci. PMID- 11759085 TI - Low prevalence of methicillin-resistant strains among Staphylococcus aureus colonizing young and healthy members of the community in Portugal. AB - Recent reports suggest that methicillin-resistant Staphylococcus aureus (MRSA) may be emerging as a community pathogen. In Portuguese hospitals, the incidence of MRSA among disease causing isolates is extremely high (48-50%). To determine the prevalence of MRSA in the Portuguese community, nasal samples were obtained from 823 draftees, 484 nonmedical university students, and 107 high-school students. In addition, throat samples were obtained from the 823 draftees and S. aureus isolates were also recovered from 283 (13%) nasopharyngeal samples obtained from 2,111 children attending day-care centers. The rate of nasal colonization of S. aureus was 34%, 25%, and 46% for draftees, nonmedical university students, and high-school students, respectively. The rate of pharyngeal colonization of the draftees was 33%. Of the 1,001 S. aureus isolates obtained, seven were MRSA and eight were borderline oxacillin-resistant S. aureus (BORSA). By molecular typing techniques, five of the seven MRSA were identified as belonging to one of three highly epidemic clones, the Brazilian, Iberian, and Pediatric clones of MRSA, which were identified as endemic in Portuguese hospitals. The eight BORSA were all members of clones previously identified in international samples. In spite of the extremely high prevalence of MRSA in Portuguese hospitals, the carriage rate of MRSA in healthy and young individuals remains low. PMID- 11759086 TI - Molecular analysis of vanA enterococci isolated from humans and animals in northeastern Italy. AB - A total of 53 vancomycin-resistant vanA-positive enterococci isolates from poultry farms (17 Enterococcus faecium; 8 Enterococcus durans) and from different hospitals (23 E. faecium; 5 Enterococcus faecalis) in northeastern Italy were compared on the basis of their antibiotic susceptibilities, their SmaI pulsed field gel electrophoresis (PFGE) patterns, and the organization of their Tn1546 related elements. Ampicillin resistance was similar in both groups of isolates (52 and 60.7%, respectively), whereas human strains were more resistant to high level gentamicin and streptomycin. A total of 52% of animal strains and 60% of human strains were resistant to tetracycline, and 56% and 46.4% to quinupristin/dalfopristin, respectively. In E. faecium and E. durans animal isolates, nine and six distinct PFGE patterns, respectively, were found: in two instances indistinguishable isolates were found from different farms. In E. faecium and E. faecalis human isolates, nine and six distinct PFGE patterns, respectively, were found; among E. faecium strains, 12 were identical or closely related and were isolates from the same hospital. Elements mediating vanA glycopeptide resistance were characterized by PCR with primers that amplified 10 overlapping fragments of Tn1546. A total of 84.6% of animal strains and 64.2% of human strains contained elements indistinguishable from the prototype Tn1546. In addition, nine different types were identified, but none was common to animal and human strains. PMID- 11759087 TI - Single or double mutational alterations of gyrA associated with fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli. AB - We looked for the presence of gyrA mutations in seven fluoroquinolone-resistant French clinical isolates of Campylobacter jejuni and Campylobacter coli. Three of the five isolates of C. jejuni and the two isolates of C. coli had high-level resistance to nalidixic acid (MICs 128-256 microg/ml) and ciprofloxacin (MICs 32 microg/ml). A gyrA mutation was found in all these isolates leading to the following substitutions: Thr86-Ile in four cases and Asp90-Tyr for one C. coli strain. One isolate had high-level resistance to nalidixic acid (MIC 64 microg/ml) but low-level resistance to ciprofloxacin (MIC 2 microg/ml) and also carried a gyrA mutation leading to a Thr86-Ala substitution. The last isolate of C. jejuni studied displayed an atypical resistance phenotype: It was resistant to high levels of ciprofloxacin (MIC 64 microg/ml) but remained fully susceptible to nalidixic acid (MIC 2 microg/ml). This phenotype was not explained by the presence of peculiar mutations in gyrA or gyrB. It carried a gyrA mutation leading to a Thr86-Ile substitution and was devoid of gyrB mutation. Despite numerous attempts with various degenerate oligonucleotide primers deduced from conserved regions of known parC genes, we were unable to amplify a corresponding sequence in C. jejuni or C. coli. First-step and second-step in vitro mutants, derived from reference strain C. coli ATCC 33559 with ciprofloxacin or moxifloxacin as selecting agents, were found to carry one and two mutations in gyrA, respectively. In contrast with the results obtained with clinical isolates, a variety of gyrA mutations were obtained in vitro. PMID- 11759088 TI - Class 1 integrons mediate antibiotic resistance in the fish pathogen Aeromonas salmonicida worldwide. AB - The presence of class 1 integrons was investigated in 38 sulfonamide-resistant strains of Aeromonas salmonicida subsp. salmonicida, atypical A. salmonicida and Escherichia coli conjugants with R plasmids originating from A. salmonicida. The strains originated from Finland, France, Japan, Norway, Scotland, Switzerland, and the United States. Additional resistance determinants in strains with class 1 integrons were also determined. Of 21 strains containing a class 1 integron, 19 had a single gene cassette, 1 strain had two cassettes, and 1 strain was found to lack an integrated gene cassette. In the integrons with single cassettes, aadA2 was present in eight strains, dfr16 in five strains, and aadA1 and dfrIIc in three strains each. In the integron with two cassettes, qacG and orfD were present. Tetracycline resistance was observed in 20 of the integron-positive strains, caused by the determinants Tet A and Tet E, in which Tet A frequently was associated with Tn1721. Class 1 integrons seem to be important in mediating antibiotic resistance also in the marine environment. The gene cassettes reported in this study are all described in bacteria associated with humans, and this demonstrates once more how the common gene pool is shared between organisms belonging to different environments. PMID- 11759089 TI - In vivo selection of oxacillinase-mediated ceftazidime resistance in Pseudomonas aeruginosa. AB - Ceftazidime-susceptible and -resistant Pseudomonas aeruginosa strains were isolated from pulmonary specimens following a treatment with ceftazidime in a patient who developed a nosocomial pneumonia. The ceftazidime-susceptible and resistant strains were clonally related and harbored a self-transferable approximately 155-kb plasmid. These isolates expressed two OXA-10-like oxacillinases, the narrow-spectrum OXA-35 and the expanded-spectrum OXA-19, respectively, differing by one amino acid substitution. This is the first example of in vivo selection of an extended-spectrum oxacillinase from a restricted spectrum oxacillinase. PMID- 11759090 TI - Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999). AB - The Italian Epidemiological Observatory (IEO), a surveillance program supported by the SmithKline Foundation, analyzed the susceptibility of 2,664 community acquired respiratory Streptococcus pneumoniae derived from over 50 clinical microbiology laboratories during 1997-1999, against 21 antibiotics adopting a quantitative methodology. Throughout these years, total penicillin resistance varied from 14.3% to 10.2%. High-level resistance has remained stable, ranging from 3.8% to 4.1%, while a decrease in low-level resistance (from 10.3% to 6.1%) has been recorded. Lack of susceptibility to macrolides ranged from 29.1% in 1997 to 25.5% in 1999. Similar figures have also been observed with tetracycline and co-trimoxazole (rates of resistance around 30%). As expected, large geographical variations in resistance rates were found for all drugs. Amoxicillin and amoxicillin-clavulanate were 100% active on penicillin-intermediate isolates. Injectable third-generation cephalosporins and carbapenems were also capable of inhibiting a large proportion of these microorganisms. Rifampin was the most potent non-beta-lactam compound tested. In contrast to the situation prevailing elsewhere, in Italian children (aged 0-5 years) presenting with respiratory conditions, the total rate of penicillin resistance (3%) was lower than that shown by the adult population (10.9%). However, lack of susceptibility to macrolides, tetracycline, and cotrimoxazole (35%, 41%, 44%) was more incident in pediatric than in adult patients (25%, 26%, 28% respectively). Strains recovered from blood in 1999 (67) were much more susceptible to penicillin (98.5%) than respiratory pneumococci (89.8%), whereas macrolides, tetracycline, and cotrimoxazole were consistently less active (75%, 67%, 64%). PMID- 11759091 TI - A microdilution plating method for population analysis of antibiotic-resistant staphylococci. AB - The microdilution plating method, using colony-forming units (CFU)/ml determinations from 10-microl droplets, was compared with the standard plate count in population analyses of methicillin-resistant and glycopeptide intermediate Staphylococcus aureus (MRSA and GISA) strains. Efficiency of plating plots yielded similar population resistance profiles for both methods with MRSA class 1-4 strains, laboratory-selected GISA strains of varying susceptibilities, two clinical GISA strains, as well as susceptible strains. A single heterogeneous MRSA, plated by both methods in 41 trials with and without 50 microg/ml oxacillin present, demonstrated no significant difference between the results of the two methods of colony counting (p > 0.05, and r = 0.67). Standard plating and microdilution plating produced mean resistant subpopulation determinations of one cell in 1.19 x 10(4) and 1.36 x 10(4), respectively. Population analyses carried out by microdilution plating require one-fourth or fewer of the plates used for standard plating, and both plating and colony counting required less time to perform. PMID- 11759092 TI - Decreased affinity of PBP3 to methicillin in a clinical isolate of Staphylococcus epidermidis with borderline resistance to methicillin and free of the mecA gene. AB - Analysis of the antibiotic binding capacity of penicillin-binding proteins (PBPs) in a group of clinical isolates of Staphylococcus epidermidis suggests that the increased level of resistance to methicillin (MIC 4.0 microg/ml) in an isolate free of the mecA gene is due to the decreased binding capacity of PBP3. PMID- 11759093 TI - Trends in birth rates: New York City 1970-1995. AB - Traditional means of assessing the problem of teen pregnancy have relied on national or state statistics. By using large geographic areas, usually comprised of a heterogeneous population, it is impossible to tell which subareas have more of a problem than others. This study focused on trends in teen birth rates at the health district level in New York City over a 25-year period to illustrate variations among ethnic groups. Teen birth rates were calculated based on vital statistics published by the New York City Department of Health. They were calculated as the number of births per 1,000 females in each of three age groups: under age 15, 15-17, and 18-19. Rates were calculated for the entire City, for four boroughs, and for selected health center districts. The decline in the birth rate among New York City teens is most significant in health districts populated by blacks. An exception is the noted increases in birth rates in districts populated predominantly by Hispanics. Data show substantial decreases among older teens compared to younger teens. Birth trends in small areas of New York City mirror trends seen nationwide. As migration changes the ethnic composition of small areas, it is important to monitor trends so that policies and programs can be targeted to those in need. PMID- 11759094 TI - Patterns of physical activity among American Indian children: an assessment of barriers and support. AB - Estimates indicate that 10% to 50% of American Indian and non-Indian children in the U.S. are obese, defined as a body mass index > or = 95th percentile of the NHANES II reference data. Pathways is a two-phase, multi-site study to develop and test a school-based obesity prevention program in American Indian schoolchildren in grades three through five. During Phase I feasibility prior to initiation of the Pathways trial, data were collected related to physical activity patterns, and the supports of, and barriers to, physical activity. Nine schools from communities representing six different tribal groups participated in this study. Multiple measures were used for data collection including direct observation, paired child interviews, and in-depth interviews and focus groups with adults. Students completed the self-administered Knowledge, Attitudes, and Behaviors (KAB) survey, and a Physical Activity Questionnaire (PAQ). Barriers to physical activity at schools included a lack of facilities, equipment, and trained staff persons for PE. Adults were not consistently active with their children, but they were highly supportive of their children's activity level. Children reported a strong enjoyment of physical activity and strong peer support to be physically active. Weather conditions, safety concerns, and homework/chores were common barriers to physical activity reported by children and adult caregivers. The information was used to design culturally and age-appropriate, practical interventions including the five physical activity programs for schoolchildren in the Pathways study. PMID- 11759095 TI - Correlates of participation and willingness to participate in anti-tobacco activities among 4th-7th graders. AB - The purpose of this study was to identify factors associated with participation and willingness to participate in anti-tobacco community activities in 4-7th grade students. A probability sample was drawn from seven regions in Florida (n = 1219). Telephone interviews assessed socioeconomic status, tobacco use, knowledge, and attitudes, and exposure to anti-tobacco school education and media campaigns. Factors related to both participation and willingness included: parental discussion of tobacco use, exposure to school courses with anti-tobacco curricula and a belief that youth could convince their friends to stop smoking. Additional participation correlates included: parental smoking status and student government activity participation. Additional willingness correlates included: exposure to anti-tobacco television campaigns, liking school, and several tobacco related knowledge and attitudinal questions. These findings suggest that exposure to community-based tobacco control programs and family discussion of tobacco use is associated with regular participation and/or willingness of youth to participate in anti-tobacco activities. PMID- 11759096 TI - The impact of a community mobilization project on health-related knowledge and practices in Cameroon. AB - The analyses presented in this paper document the impact of a community mobilization effort in Cameroon. Between 1997 and 1998, a local non-governmental organization worked with community associations, Njangi, in one urban and one rural location to promote knowledge and positive practices concerning family planning, sexually transmitted diseases, and treatment of common childhood diseases. Based on a multi-tiered structure, the project involved selecting and training two prominent and influential members of each community as "relais" or middlemen. The "relais" then trained mobilizers from participating Njangis to provide relevant information and help to mobilize their fellow members in favor of the positive attitudes and practices promoted by the project. The project was evaluated using baseline and follow-up measurement of pertinent indicators, and service statistics. Results suggest that the intervention had significant influence in the rural location with noticeable positive effects on knowledge and practices of family planning, knowledge and attitudes about HIV/AIDS and STIs, and use of health services. In the urban location, for programmatic and extraneous factors, the intervention was not effective. The paper discusses the lessons learnt from the intervention and offers pertinent suggestions for replicating the intervention in rural settings. PMID- 11759097 TI - Knowledge and awareness of tuberculosis among pre-university students in Trinidad. AB - The purpose of the study was to determine the level of knowledge and attitudes among pre-university students in Trinidad and Tobago on the pre-disposing factors and prevention of tuberculosis and the management of persons with the disease. More than 90% (542 of 600) of participating students from nine secondary schools duly completed the self-administered questionnaires. Two-thirds of the students were girls (336) and the rest were boys (206). The ages of the participants ranged from 16-19 years and more than 82% of them belonged to the 17-18 year old age group. The least represented was the 19 year olds. The study showed that although 92.8% had heard of tuberculosis, overall knowledge about the disease was generally poor. The majority of students (77.5%) believed the disease could be prevented, but 10.3% knew of the BCG vaccine and only 11.1% knew about the Mantoux skin test. The study also demonstrated the need for renewed efforts in health education for the public, clarifying areas of misunderstandings about important and common diseases like tuberculosis, in developing countries. PMID- 11759098 TI - The role of the mouthguard in the prevention of sports-related dental injuries: a review. AB - OBJECTIVES: This paper examines the literature dealing with oral-facial injuries received during participation in sport and the possibilities open to athletes for their prevention. In particular, the paper examines five different aspects of this topic: the risk of dental injury while playing sports, the role of the mouthguard in preventing injury, types of athletic mouthguard, implications for patients undergoing orthodontic treatment and behavioural aspects of mouthguard wear. RESULTS: It is clear from this review that participation in a number of sports does carry a considerable risk of sustaining dental injury, not only in the so-called contact sports such as rugby and hockey, but also in less obviously dangerous sports such as basketball. Although some evidence exists to the contrary, the majority of studies have found the mouthguard to be the most effective way of preventing such injuries. It is also clear that the custom fabricated mouthguard, in particular the pressure-laminated variety, is seen to afford most protection. Athletes undergoing orthodontic treatment present a particular problem as they are potentially at greater risk of injury because of increased tooth mobility and the presence of orthodontic appliances. The fabrication of mouthguards for these patients is also problematic and the literature covering this is reviewed. As with other preventive measures, mouthguard usage is often less than the dental profession would like; the reasons for this are explored in a small number of studies. CONCLUSION: While much progress has been made in this area, the profession could do much more to promote the greater use of mouthguards. PMID- 11759099 TI - Sensitivity to local anaesthetics among asthmatic children. AB - OBJECTIVES: Although true allergic reactions to local anaesthetics are rare in the general population, the importance of the problem among asthmatic children has yet to be documented. SAMPLE AND METHODS: Skin prick, intradermal and incremental challenge tests with lidocain were performed in 157 asthmatic children aged 8-15 years and compared with 72 nonasthmatic children of a similar age. All of the asthmatic subjects were allergic to at least one allergen, most frequently pollens and house dust mites. Prick testing began with an undiluted solution in patients without a history of allergy and with 1:100 dilution in those with a reaction history. Following negative prick testing, intradermal or incremental challenge tests were performed. RESULTS: A total of 125 patients (80%) had been given local anaesthetics in the past, only three children gave history of an adverse local reaction. At the end of the tests, none of the subjects including controls, were found to have immediate or delayed-type allergy to lidocain. CONCLUSIONS: Local anaesthetic allergy does not seem to be a serious problem among asthmatic children and testing in all asthmatic children is not warranted. Those with an adverse reaction history to local anaesthetics should be tested with these drugs. PMID- 11759100 TI - Microleakage of three sealants following conventional, bur, and air-abrasion preparation of pits and fissures. AB - OBJECTIVES: The aim of this study was to compare the microleakage of a filled sealant with a drying agent (UltraSeal XT plus), a filled sealant (Prismashield) and an unfilled sealant (Delton), after conventional, bur, and air-abrasion tooth preparation techniques. SETTING: The study was completed in a clinical setting at the Simulated Practice Environment Clinic, School of Dentistry, University of Western Ontario, London, Ontario, Canada. SAMPLE AND METHODS: One hundred and eighty extracted teeth were cleaned and divided randomly into three groups. Group 1 was prepared using acid etch only. Group 2 was prepared with a 1/4 round bur in a low-speed handpiece followed by acid etching. Group 3 was prepared with high speed (120PSI) microabrasion using 27 microm alpha-alumina particles in a Midwest Airtouch unit. The teeth in each group were randomly assigned to one of the three subgroups according to the sealant applied. Subgroup A was sealed with a filled sealant with drying agent, B with a filled sealant only, and C with an unfilled sealant. All teeth were stored in artificial saliva for 7 days at 37 degrees C. After this, the teeth were coated with nail varnish 1 mm from the sealant and immersed in 1% methylene blue dye for 48 h at 37 degrees C. Each tooth was sectioned at four locations buccolingually and a total of 665 sections were ranked (0-3) for microleakage. Statistical analysis was completed using the Chi squared test and Fisher's exact test. RESULTS: UltraSeal XT plus, the filled sealant with drying agent, showed significantly less microleakage than the other two sealants (P < 0.05). Delton, the unfilled sealant, showed significantly less microleakage than Prismashield, the filled sealant (P < 0.05). Air abrasion with acid etch showed significantly less microleakage than either bur with acid etch or acid etch alone. There was however, no significant difference between the bur and acid etch tooth preparations (P < 0.05). CONCLUSIONS: UltraSeal XT plus was the most effective sealant for preventing microleakage in this study. The most successful method of preparation was air abrasion with acid etch. PMID- 11759101 TI - The distribution of stimulated saliva in children. AB - OBJECTIVES: The need for an adequate quantity of saliva to maintain oral health has been widely reported. It is not only the quantity that is important, but also how the saliva is distributed once it enters the mouth. Several studies have looked at how saliva is distributed around adult mouths. The aim of this experiment was to describe the distribution of stimulated saliva around the mouth in children. SAMPLE AND METHODS: In order to demonstrate the distribution of saliva around the mouth under stimulated conditions, 25 child subjects were asked to chew a piece of chewing gum containing 1.5 mg erythrosin for 3 min on one side of the mouth. The distribution of dye in the mouth was recorded on standardized charts. RESULTS: In all cases, dye was present ipsilateral to the chewing side. In 13 cases (52%) the dye did not cross the midline and of the remaining 12 children the dye only reached the contralateral canines in four of them (16%). CONCLUSIONS: Evidence is presented which suggests that during unilateral chewing in children, saliva is not well distributed around the mouth and has a tendency to stay on the side of the mouth from where it was secreted (P < 0.01). PMID- 11759102 TI - Oral health in liver transplant children administered cyclosporin A or tacrolimus. AB - BACKGROUND: Immunosuppression by cyclosporin A (CsA) is associated with adverse side-effects, including nephrotoxicity, neurotoxicity and gingival overgrowth. Tacrolimus (TAC/FK506) is a new immunosuppressive agent, recently approved for use in solid-organ transplants. The mode of action of TAC is similar to that of CsA and the toxicity profile of CsA is duplicated by TAC. The effect of TAC on the gingival tissue is not yet conclusive. SAMPLE: Gingival overgrowth was assessed in 30 liver transplant children, 20 boys and 10 girls, aged 2-19 years. Seventeen children (10 boys, seven girls) were on a CsA-based immunosuppressive regimen whereas 13 children (10 boys, three girls) were on TAC for at least 1 year (mean 4.3 +/- 2.7). RESULTS: In the CsA group, 35% of children exhibited gingival overgrowth characterized by one or more units with increased sulcus probing depth (> or = 4 mm), i.e. pseudopockets. In contrast to the CsA group, none of the children in the TAC group exhibited gingival overgrowth. The occurrence of enamel hypoplasia was observed in 11 children (36%) and enamel opacities were found in 23 children (76%). Six of the 12 children (50%) with hyperbilirubinaemia biliary atresia exhibited a marked greenish discoloration of the teeth. Caries experience (dmft/DMFT) among these children was 2.0 +/- 2.8. CONCLUSION: No difference in caries experience or enamel defect was observed between the CsA and TAC group. PMID- 11759103 TI - The relationship between erosion, caries and rampant caries and dietary habits in preschool children in Saudi Arabia. AB - OBJECTIVES: The aim of this study was to investigate the possible association between dental erosion and caries, and variables including socio-economic status, reported dietary practices and oral hygiene behaviour, in a sample of children in Jeddah, Saudi Arabia. A cross-sectional study including dental examination and questionnaire survey was carried out at a number of kindergartens. SAMPLE AND METHODS: A sample of 987 children (2-5-year-olds) was drawn from 17 kindergartens. Clinical examinations were carried out under standardized conditions by a trained and calibrated examiner (MAM). Information regarding diet and socio-economic factors was drawn from questionnaires distributed to the parents through the schools. These were completed before the dental examination. RESULTS: Of the 987 children, 309 (31%) showed signs of erosion. Caries were diagnosed in 720 (73%) of the children and rampant caries in 336 (34%). Vitamin C supplements, frequent consumption of carbonated drinks and the drinking of fruit syrup from a feeding bottle at bed- or nap-time when the child was a baby, were all related to erosion. Consumption of carbonated drinks and fruit syrups was also related to caries but they were part of a larger number of significant factors including socio-demographic measures and oral hygiene practices. CONCLUSIONS: There was no clear relationship between erosion and social class, or between erosion and oral hygiene practices; the reverse was true for caries. Dietary factors relating to both erosion and caries and/or rampant caries were found in this sample of children. PMID- 11759104 TI - Incidence of caries in an infant population in Mostoles, Madrid. Evaluation of a preventive program after 7.5 years of follow-up. AB - OBJECTIVE: To assess the efficacy and effectiveness of a dental-health programme after 7.5-years of follow-up. DESIGN: The study follows a prospective cohort design without randomization. POPULATION AND METHODS: The study group cohort consisted of 547 school children, 266 girls and 281 boys, the control group was composed of 237 school children, 121 girls and 116 boys. Dental examinations were carried out using WHO criteria. Preventive measures included health education, a weekly mouth rinse using sodium fluoride (NaFI) at 0.2% concentration, fissure sealants to first permanent molars and topical application of fluoride gel. The outcomes using different indices of tooth decay and socio-demographic variables were compared between study and control groups and statistical significance determined through the Mann-Whitney U-test. Logistic regression was used in the multivariate analysis. RESULTS: There were statistically significant differences between cohorts in the indices of decay. The mean DMFT value for study group children was 1.52 and for first permanent molars (DMFM) 1.10 per child, mean DMFS was 2.09. In the control group, values were DMFT-3.07, DMFM-2.03 per child, DMFS 4.33. Logistic regression showed the preventive programme to have a significant independent effect. CONCLUSION: The preventive programme had been effective and had a clear protective effect. PMID- 11759105 TI - A study in two centres of variations in the time of apical barrier detection and barrier position in nonvital immature permanent incisors. AB - OBJECTIVES: To study barrier formation in nonvital, immature permanent incisors being treated using the apexification technique in two centres, and to establish the effect of the frequency of change of calcium hydroxide (CaOH) on barrier detection times. DESIGN: A retrospective study of the time of detection and the position of barriers. RESULTS: There were no significant differences between the two centres in terms of the average frequency of change of each CaOH dressing, the distribution of barrier detection times or the position of barriers (P > 0.05). There was a total of 107 teeth and the time of barrier detection was significantly earlier in more frequently dressed teeth (P = 0.013). Of the teeth with a barrier detection time of less than 9 months, 60.7% were dressed more frequently than every 3 months, as opposed to 39.1% of teeth with longer barrier times (P = 0.027). The mean time of barrier detection for all cases was 43.3 weeks. The majority of barriers were located at or near the apex. CONCLUSION: The frequency of change of CaOH can increase the speed of barrier detection but does not appear to affect the position. PMID- 11759106 TI - Radicular cyst associated with a primary molar following pulp therapy: a case report. AB - A radicular cyst arising from the primary second molar and causing displacement of the permanent successor to the lower border of the mandible, with accompanying buccal expansion, was examined clinically and radiographically. Extraction of the primary molar and extirpation of the cyst led to uneventful healing. The primary molar had received pulp treatment with therapeutic agents approximately 1.5 years prior to the patient's first visit. The relationship between pulp treatment and rapid growth of the radicular cyst is discussed. PMID- 11759107 TI - Analysis of local and systemic inflammatory responses induced by polymicrobial peritonitis in mice. AB - BACKGROUND: Abdominal sepsis induces a local production of proinflammatory mediators that may trigger both septic shock and organ-system dysfunction. AIMS: The present study analyzed exudation, cell migration, and CD11a and CD18 subset cells of both local and systemic responses induced by fecal peritonitis in mice. METHODS: Animals were anesthetized and, after performing a midline incision in the abdomen, the cecum was ligated and punctured twice with a needle. Sham operated animals were included. Some groups were previously treated with Evans blue dye (intravenously) to further evaluate the amount of tissue and abdominal cavity leakages. RESULTS: Fecal peritonitis triggered a local inflammatory reaction with an increased number of leukocytes and exudation between 6 and 48 h (p < 0.01). Although CD11a/CD18-positive cells in the abdomen peaked after 24h, a significant decrease of them was detected after 48 h (p < 0.05). At the studied period of time (6-48 h), different degrees of exudation in several organs occurred, whereas a significant late recruitment (24 h) of CD11a/CD18 cells into the lungs was observed. CONCLUSIONS: In this model, cell migration and exudation at the site of injury occurred in parallel. However, in the lungs, the recruitment of leukocytes that express CD11a/CD18 adhesion molecules constitutes a non-dependent event in relation to fluid leakage accumulation at this site. PMID- 11759108 TI - 17beta-estradiol promotes the synthesis and the secretion of annexin I in the CCRF-CEM human cell line. AB - AIMS: Annexin I (ANXA1), a 37kDa member of the annexin family of Ca2+-binding and phospholipid-binding proteins, is particularly abundant in various populations of peripheral blood leukocytes. Since this protein modulates the anti-inflammatory actions of the steroid hormones, the purpose of this study was to investigate the effects of the female sex steroid hormone, 17beta-estradiol (E2beta), on the synthesis and secretion of ANXA1 in the human CCRF-CEM acute lymphoblastic leukemia cell line. METHODS: Complementary reverse transcription-polymerase chain reaction and Western blot assays were performed to study the effect of E2beta on the expression of mRNA and protein ANXA1, respectively. RESULTS AND DISCUSSION: Treatment of CCRF-CEM cells with E2beta, for 30 min, stimulated the synthesis of ANXA1 mRNA molecules, and increased the cellular level of ANXA1 protein. Moreover, when the cells were incubated with E2beta under the same experimental conditions, a significant increase in the amount of ANXA1 secreted from the cells was also detected. ICI 182,780, a selective inhibitor of the intracellular estrogen receptor, had no effect on the E2beta-stimulated expression and externalisation of ANXA1. Taken together, these results indicate that E2beta induces de novo synthesis of ANXA1 and stimulates its secretion in the CCRF-CEM cell line, apparently through a mechanism independent of the intracellular estrogen receptor. PMID- 11759109 TI - Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients. AB - OBJECTIVE: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)) and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long term response to therapy. METHODS: In 55 patients with chronic hepatitis C virus (HCV), 33 treated with interferon (IFN) and 22 treated with IFN + ribavirin, sera was collected prior to treatment, at 3 + 6 months of therapy and 6 months post treatment. Levels of ICAM-1, VCAM-1 and hyaluronic acid were correlated with alanine aminotransferase levels, HCV-RNA-polymerase chain reaction status and histological fibrosis scoring. RESULTS: A decrease in ICAM-1 levels at 3 and 6 months of therapy, compared with pretreatment levels, was observed in responders to IFN + ribavirin therapy but this decrease in ICAM-1 levels was not evident following cessation of treatment. Hyaluronic acid levels, in both treatment groups, did not differ significantly between responders and non-responders. Hyaluronic acid levels did correlate, significantly, with degree of fibrosis whereas VCAM-1 levels were marginally increased only in patients with moderate (grade III) fibrosis. CONCLUSIONS: Monitoring of VCAM-1 and hyaluronic acid, during antiviral therapy, does not differentiate between responders and non responders. A decrease in ICAM-1 levels during IFN + ribavirin treatment is associated with response to therapy, and its efficacy in predicting long-term response should be further substantiated. PMID- 11759110 TI - Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro. AB - Heparanase activity is correlated with the metastatic potential of several cancer cells and is a key enzyme in the breakdown of tissue barriers. It is also involved in the regulation of growth factor and cytokine activity. However, little is known about the factors that induce heparanase in cancer cells. We investigated the effect of three growth factors, platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), on heparanase mRNA induction in lung cancer cells in vitro. In addition, we examined the effect of erythromycin (EM) and clarithromycin (CAM), which are 14 membered ring macrolide antibiotics that act as biological response modifiers, on the expression of heparanase mRNA induced by growth factors. PDGF, HGF and bFGF stimulated cell migration activity and enhanced the expression of heparanase mRNA in the human lung adenocarcinoma cell line A549. Via different mechanisms, EM and CAM modulate the induction by these factors of heparanase mRNA expression on A549 cells. EM also significantly suppressed A549 cell migration induced by PDGF and HGF, and CAM significantly suppressed A549cell migration induced by bFGF. The results suggest that the growth factors PDGF, HGF and bFGF are important inducers of heparanase in potentially invasive and metastatic cancer cells. The suppressive effect of heparanase mRNA expression by EM and CAM may have interestingtherapeutic applications in the prevention of metastasis. PMID- 11759111 TI - Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa. AB - Secretory leukocyte protease inhibitor (SLPI) is a well-known protease inhibitor. Its function is thought to be protease/protease-inhibitor balance. Free proteolytic activity, mainly pancreatic elastase, anionic trypsin and granulocytic elastase, has been demonstrated in faecal extracts from patients with ulcerative colitis. We wanted to verify that SLPI is actually secreted from normal human colonic mucosa. Also, we wanted to ascertain whether studies of SLPI secretion based on punch biopsies were dependent on biopsy area or on biopsy circumference. Normal colonic mucosa was sampled during surgery for colonic cancer. A total of 36 samples from four patients were used. Mucosa preparation was carried out using a punch biopsy technique, and samples of 3, 4 and 6 mm diameter were used. All media contained SLPI at varying concentrations. When expressed in terms of the sample area, the secretion per millimetre-squared seemed to decrease with increasing area. When calculated as secretion per circumference, secretion seemed to be constant. In conclusion, SLPI was secreted from normal human colonic mucosa. The SLPI secretion seemed dependent on the circumference of the biopsy rather than on the area of the biopsy. PMID- 11759112 TI - Rapid and simple determination of histamine-N-methyl transferase activity by high performance liquid chromatography with UV detection. AB - A rapid, simple and low-cost assay method of histamine-N-methyltransferase activity was developed. Methylhistamine, which was separated from the enzymatic reaction system on reversed-phase high-performance liquid chromatography using an ion-paired chromatographic technique, was detected spectrophotometrically at 226 nm. The mobile phase used for the separation of methylhistamine was 0.05M NH4H2PO4 (pH 3.0) containing 2 mM of sodium octanesulfonate. The new assay technique could detect methylhistamine as an enzyme activity product of histamine N-methyltransferase in the brain and kidney of rats. Chloropheniramine maleate, an antihistamine, activated the histamine-N-methyltransferase. Whether neurotransmitter or neuromodulator, the role of histamine in the brain has not yet been made clear. Therefore, the present method could be applicable for the enzymatic investigation of histamine metabolism in central nervous system or inflammatory reactions. PMID- 11759113 TI - Off-pump vs. on-pump: time to randomize! PMID- 11759114 TI - Myocardial hibernation--land of ignorance. PMID- 11759115 TI - Detection of myocardial damage - are the troponins the ultimate solution? AB - Biochemical markers of myocardial damage are together with the clinical history, the physical examination and the 12-lead ECG key elements in the clinical evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). In this situation the detection of myocardial damage, even very minor, is of importance, not only for diagnosis, but also for risk assessment and selection of treatment. The new markers of myocardial damage. troponin T and I, have been shown to offer some advantages over the conventional markers in ACS and there is also an increasing interest for troponins in other clinical situations, e.g. after surgery and percutaneous coronary intervention. This paper will discuss the role of troponins in these different clinical situations. PMID- 11759116 TI - Epidemiological consequences of introducing new biochemical markers for detection of acute myocardial infarction. AB - OBJECTIVE: To evaluate how the use of different biochemical markers of myocardial injury affects the recorded numbers of cases of diagnosed acute myocardial infarction (AMI) and unstable angina pectoris (UAP) and also the observed in hospital mortality of AMI. DESIGN: 442 patients admitted with suspected acute coronary syndrome (ACS) were studied. Based on the World Health Organization (WHO) criteria, the patients were classified into five categories: acute Q-wave myocardial infarction (QMI): acute non-Q-wave myocardial infarction (NQMI); UAP; stable angina pectoris; and chest pain of non-cardiac origin. RESULTS: Using total creatine kinase (tCK) as the "gold standard" for diagnosis, we found 172 AMI. 100 UAP and 170 with other diagnoses. If we used CK-MB (>6 microg/L) or cTnl (> 1 microg/L) for diagnosing AMI, the numbers of AMI increased significantly by 50 (29%) and 64 (37%), respectively. Using tCk, CK-MB or cTnl for diagnosing AMI, the observed in-hospital mortality was 14%, 11% and 10%, respectively. The group of patients with elevated cTnl but negative tCK had similar long-term survival as the group of patients with cTnI >30 microg/L, comprising 95% of the patients with the diagnosis AMI based on tCK. CONCLUSION: The introduction of new biochemical markers for detection of AMI may lead to significant changes in the recorded incidence and in-hospital mortality of AMI. New biochemical markers of myocardial injury must be validated against the traditional markers as they are introduced into clinical practice by the new diagnostic criteria. PMID- 11759117 TI - Diminished circadian variation in heart rate variability before surgery in patients developing postoperative atrial fibrillation. AB - OBJECTIVE: To evaluate the role of the autonomic nervous system for the development of atrial fibrillation (AF) after coronary artery bypass surgery. DESIGN: Eighty patients without a previous history of AF were included. The sympathetic and parasympathetic activity were evaluated by the analysis of heart rate variability (HRV) in the frequency domain from 24-h Holter recordings and by measuring neuropeptides (neuropeptide Y, chromogranin A, chromogranin B, and pancreatic polypeptide (PP)) and catecholamines, obtained pre- and postoperatively. RESULTS: Preoperatively, patients (36.3%) developing AF postoperatively showed a statistically significant less circadian variation in the HRV variables, the high-frequency (HF) component (p = 0.013) and the low frequency (LF)/HF ratio (p = 0.007), than patients remaining in sinus rhythm. The HF component and PP. both reflecting parasympathetic activity, and all other variables in the frequency domain, decreased significantly after surgery in both patient groups (p < 0.0001). Although catecholamines increased significantly postoperatively in both patient groups, neither catecholamines nor neuropeptides expressing sympathetic activity, differed between the two groups. PP was, however, significantly higher in patients with postoperative AF than in those with sinus rhythm postoperatively on day 1. CONCLUSION: The diminished circadian variation in HRV before surgery and the indirect signs of a higher parasympathetic activity in patients developing postoperative AF compared with patients remaining in sinus rhythm, may indicate a propensity for AF. PMID- 11759119 TI - Age and angina as predictors of quality of life after myocardial infarction: a prospective comparative study. AB - OBJECTIVES: The objectives were to compare quality of life (QoL) after first myocardial infarction with an age- and sex-adjusted normative population and to test whether the 1-month QoL had predictive properties. DESIGN: QoL was assessed by self-administered questionnaires (SF-36 and Cardiac Health Profile) 1, 3 and 6 months after index-event. Participants were 60 consecutive patients (20% women) with a mean age of 58 +/- 7.4 years. RESULTS: Patients > or =59 years improved in Physical (PCS) and Mental Component Summary (MCS), scoring comparable to community norms at 6 months. However, patients <59 years improved in PCS but not in MCS. and scored significantly below community norms in both PCS (x = 44.7, CI 40.6-48.7 vs x = 50.3, CI 49.3-51.4) and MCS (x = 45.9, Cl 41.8-49.9 vs. x = 51.3, CI 50.3-52.4) at 6 months. Predictors for MCS were age (p = 0.025) and Vitality (p = 0.020) both positively related to QoL. Predictors for PCS were Physical Function (p = 0.003) and CCS score (p < 0.001) where angina grade was negatively related to QoL. CONCLUSION: Because of impaired mental recovery in younger post-infarction patients, their need of special attention in the rehabilitation process must not be overlooked. PMID- 11759118 TI - 99mTc-Sestamibi SPECT is a useful technique for viability detection: results of a comparison with NH3/FDG PET. AB - OBJECTIVE: Assessment of myocardial viability by 99mTc-Sestamibi Single Photon Emission Computerized Tomography (SPECT) has been suggested as a more readily available and cheaper alternative to Positron Emission Tomography (PET) with 13N ammonia (NH3) and 18F-fluoro-deoxy-glucose (FDG). We hypothesized that a semi quantitative evaluation by SPECT could delineate myocardial viability with an acceptable concordance to PET. DESIGN: Fifty patients (age 57+/-7 years; ejection fraction 28 +/- 8%), with ischemic cardiomyopathy, underwent SPECT and PET imaging in random order. Viability by SPECT was defined as a defect size <50% of the segment area, or a defect representing > or =50% of the segment but with a mean activity > or =50% of peak activity. PET viability was defined as a perfusion score >2 and FDG score < or =2 (five-point scale, 0 = normal, 4 = absent activity). RESULTS: By segmental comparison to PET. SPECT yielded a sensitivity and specificity of 87% and 82% for detection of viable myocardium. The positive and negative predictive values were 96% and 58%, respectively. CONCLUSION: In patients with severe ischemic cardiomyopathy 99mTc-Sestamibi SPECT can delineate viable myocardium with an acceptable segmental concordance to NH3/FDG PET. PMID- 11759120 TI - Depression and associated factors in coronary heart disease. AB - OBJECTIVE: To investigate whether depression was associated with cardiac status and socio-demographic factors in patients with coronary heart disease (CHD). METHODS: The sample consisted of 144 symptomatic patients with CHD. For screening depression the Beck Depression Inventory was administered on the day before elective coronary angiography. RESULTS: Twenty-four per cent of patients had probable depressive disorder, but none of them had been previously identified as suffering from depression, or been treated for depression. Alexithymia and dissatisfaction with life were common in depressed patients. Logistic regression analysis showed that neither the cardiac status nor sociodemographic factors were associated with depression. CONCLUSION: Depression is a common finding and should be looked for independently of other risk factors in patients with CHD. PMID- 11759121 TI - Better preserved pulmonary endothelium-dependent vasodilation with off-pump coronary surgery. AB - OBJECTIVE: To investigate if endothelium-dependent vasodilation in the pulmonary circulation was better maintained after off-pump coronary artery bypass grafting (CABG). An impaired pulmonary vascular response to acetylcholine has been observed after cardiopulmonary bypass (CPB) in children, adults and experimentally. DESIGN: Fourteen patients operated off-pump were compared with 21 patients undergoing conventional CABG with CPB. The indexed pulmonary vascular resistance was measured before and during an infusion of acetylcholine, aiming at a concentration of 10(-6) mol/l in the pulmonary artery. Twelve patients operated on-pump received saline instead of acetylcholine. RESULTS: Before surgery pulmonary vascular resistance decreased during infusion of acetylcholine by 28% and 25% in the off-pump and on-pump groups. After surgery the decrease was 16% and 6%, respectively (p = 0.028 and p < 0.001, compared to preoperative response). The response did not differ between the two groups before, but did so after surgery (p = 0.01). Saline had no effect. CONCLUSION: The better maintained endothelium-dependent vasodilation in the off-pump group indicated less endothelial dysfunction. PMID- 11759122 TI - Localization of the initial fibrillatory cycle in patients with paroxysmal atrial fibrillation. AB - BACKGROUND: Recent reports suggest the presence of conduction delay in the posterior septal region during sinus rhythm in patients with lone paroxysmal atrial fibrillation (AF). OBJECTIVE: To explore the location of intra-atrial conduction delay associated with initiation of AF. DESIGN: In 8 lone AF patients (51 +/- 10 years), 20 AF paroxysms were induced during electrophysiological examination. Bipolar electrograms were acquired from a 10-polar catheter in the coronary sinus (CS), a 4-polar His bundle catheter, and a 20-polar Halo catheter in the right atrium. RESULTS: Induced AF paroxysms showed earliest registered atrial activity in interatrial septum (IAS) or proximal CS in 17 cases (85%). Conduction delay at the posterior IAS or proximal CS accompanied induction of 18 AF paroxysms (6 patients). Atrial activation sequence at the beginning of the AF paroxysms was stable and reproducible in six repeatedly induced AF episodes (3 patients). CONCLUSION: In lone AF patients, induction of AF is associated with conduction disturbances in the IAS and proximal CS regions. PMID- 11759123 TI - Coagulation system activity before coronary artery bypass surgery for unstable angina. AB - OBJECTIVE: To measure coagulation activity immediately prior to coronary artery bypass surgery. Previous reports have shown that a hypercoagulable state and reduced fibrinolytic activity increase the risk of postoperative graft failure. DESIGN: Fifty patients with unstable angina and ongoing low-molecular-weight heparin antithrombotic treatment for a median of 4 days and 25 stable patients undergoing elective surgery were included. RESULTS: Antithrombin levels were significantly lower whereas fibrinogen and plasminogen activator inhibitor-1 levels were higher in the unstable patients than in the stable patients. Median preoperative levels of thrombin-antithrombin complex (TAT), prothrombin fragment1+2 (F1+2), fibrin D-dimers and beta-thromboglobulin did not differ significantly in unstable and stable patients. There were signs of activated coagulation with elevated levels of TAT and F1+2 before the operation in half of the unstable patients, who had had chest pain at rest within 48 h preceding the operation and also in one-third of patients undergoing elective surgery. CONCLUSION: A hypercoagulable state may be present in unstable as well as in stable angina pectoris patients accepted for coronary artery bypass surgery. PMID- 11759124 TI - Thoracic vascular injuries: a major problem in trauma. AB - OBJECTIVE: We present a review of our experience in the management of thoracic vascular injuries during the past 10 years in one of Sweden's busiest emergency departments, with morbidity and mortality as the main outcome measures. DESIGN: Of eight patients who sustained chest trauma with thoracic vascular injuries, six presented with shock. Angiography was the gold standard in diagnosing aortic and subclavian injuries. RESULTS: Lesions of the inferior vena cava, left internal mammary artery, and intercostal vessels were detected only at surgery. Two patients died of exsanguination. Managing thoracic vascular injuries is still difficult and challenging for thoracic and trauma surgeons. CONCLUSION: Early thoracotomy is important for salvage of patients with chest-wall vascular injury. Despite our limited experience, which is characteristic for Scandinavian and European countries, our results were satisfactory. PMID- 11759125 TI - The effect of nitrous oxide on laryngeal mask cuff pressure. AB - During general anesthesia with the laryngeal mask airway (LMA), a significant increase in cuff pressure due to diffusion of nitrous oxide through the cuff wall occurs. This descriptive clinical study was conducted in a university teaching hospital ambulatory surgical center with 100 patients (ASA physical status, I III; age, 5 months to 76 years; weight, 5.8-146.3 kg) undergoing general anesthesia with an LMA. The airway pressure at which the LMA seal was broken (leak pressure) was determined immediately after the insertion of the LMA. The LMA leak pressure was determined by closing the circuit pop-off valve and recording with a stethoscope at the neck the pressure at which the gas was first heard to escape around the LMA. The LMA cuff pressure was determined by connecting the check valve of the LMA pilot balloon to a sphygmomanometer. The mean LMA cuff pressure increased 16 +/- 8.2 mm Hg (1- to 30-minute group), 38.11 +/- 15.87 mm Hg (31- to 60-minute group), 39.53 +/- 16.9 mm Hg (61- to 90-minute group), 42.63 +/- 20.36 mm Hg (91- to 120-minute group), and 44.25 +/- 14.03 mm Hg (120- to 350-minute group). This study demonstrated that there was a gradual increase in the cuff pressure well over a 3-hour period during nitrous oxide and oxygen anesthesia. PMID- 11759126 TI - Anesthetic implications of subacute left ventricular rupture following acute myocardial infarction: a case report. AB - Rupture of the free wall of the left ventricle, a relatively common complication of acute myocardial infarction, is associated with a high mortality rate. The clinical course can vary from catastrophic, that is death, to incomplete rupture with the formation of a pseudoaneurysm. Subacute rupture is a condition that demands expeditious diagnosis and surgical repair if the patient is to survive. Surgical repair can be difficult at best. This article reports a case of subacute rupture of the left ventricle that was successfully repaired using a novel surgical technique and discusses the anesthetic implications surrounding the case. PMID- 11759127 TI - Newer trends in monitoring: the esophageal Doppler monitor. AB - The esophageal Doppler monitor is a recent development in hemodynamic monitoring that is used for surgical patients. It is relatively noninvasive and measures descending aortic blood flow by the Doppler effect. A comparison of this new monitor with the pulmonary artery catheter is cited numerous times throughout the literature and overall correlates well. Studies of the esophageal Doppler monitor show it to be a safe addition to operating room monitors for use by the anesthetist. PMID- 11759128 TI - The dose-related effects of bolus esmolol on heart rate and blood pressure following laryngoscopy and intubation. AB - Many researchers have studied esmolol and its effects on heart rate and blood pressure. All studied relatively large doses of esmolol. Therefore, the purpose of the present study was to determine whether small doses of esmolol would blunt the transient increases in blood pressure and heart rate caused by laryngoscopy. This double-blind, prospective, randomized study included 61 subjects. The subjects were randomized to 1 of 3 groups: group 1 received esmolol, 0.2 mg/kg; group 2 received esmolol, 0.4 mg/kg; and group 3 received saline placebo. Groups 1 and 2 had smaller increases in heart rate than group 3. We also found that the 0.4 mg/kg dose significantly blunted the increase in mean arterial pressure seen in group 3. This study shows that small doses of esmolol may block the increases in heart rate and blood pressure resulting from laryngoscopy and intubation. PMID- 11759129 TI - Acute circulatory and respiratory collapse in obstetrical patients: a case report and review of the literature. AB - Venous air embolism is the entrapment of air into the venous system producing signs and symptoms due to obstruction of pulmonary arterial blood flow. We present a healthy, 27-year-old, full-term parturient admitted for postdate induction of labor. Cesarean delivery was required following fetal distress. During delivery, the mother became bradycardic and required advanced cardiac life support for resuscitation. Serial hemoglobin values, electrocardiograms, echocardiograms, and a magnetic resonance image of the head were all normal. No fetal squamous cells were found in the patient's blood. She required 6 days of ventilation, was successfully extubated, and was discharged 14 days after the cesarean delivery. The differential diagnosis in this patient's care centered on a pulmonary embolic event. Thromboembolism was unlikely, based upon the patient's rapid clinical improvement without definitive therapy for thrombotic disease or detection of peripheral thrombosis. Amniotic fluid embolus was unlikely, although not excluded, by the absence of fetal cells in the maternal circulation and the lack of an accompanying intravascular coagulopathy. Air embolism may occur in up to 50% of women undergoing cesarean delivery. A lethal embolism may follow a bolus of 3 to 5 mL/kg of air. Chief among the many symptoms of air embolism are tachypnea, chest pain, and gasping. The diagnosis may be facilitated by precordial Doppler monitoring, transesophageal echocardiography, or by the identification of air when aspirating from a right heart catheter. Management includes optimum patient positioning, aspiration of air, discontinuation of nitrous oxide, administration of 100% oxygen, and flooding the surgical site with saline to avoid further air entry. Preventive strategies are also discussed. PMID- 11759130 TI - A comparison of nurse anesthesia practice types. AB - The present study examined the differences between anesthesia care team (ACT) and non-ACT practice types. Six practice variables were analyzed. We prepared and distributed a 13-item questionnaire to 1,000 practicing Certified Registered Nurse Anesthetists (CRNAs) with a 44.4% response rate. Data analysis revealed that nurse anesthetists in ACT practices had fewer years of experience and were younger than non-ACT nurse anesthetists (alpha = 0.05). Also, a significantly greater percentage of ACT nurse anesthetists were female, held master-level degrees, and practiced in urban and metropolitan locations. This also was true for placement of laryngeal mask airways and arterial lines, and in providing anesthesia for cardiopulmonary bypass, pediatric, intracranial, and trauma cases. However, a significantly greater percentage of non-ACT nurse anesthetists placed epidurals and central lines and were involved in pain management and critical care consultations. Income was significantly greater for non-ACT nurse anesthetists as well, but they worked more hours per week on average. Lastly, evaluation of employment arrangements showed that more than 91% (n = 361) of ACT nurse anesthetists were employees, and only 4% (n = 17) were self-employed. However, only 49% (n = 24) of non-ACT nurse anesthetists were employees, and almost 43% (n = 21) were self-employed. The present study demonstrates that significant differences exist between the 2 nurse anesthesia practice types examined. As nurse anesthesia practice arrangements continue to change and fewer CRNAs are hospital employed, each nurse anesthetist must be aware of current practice trends and understand the alternatives. PMID- 11759131 TI - AANA journal course: update for nurse anesthetists--the ruddy globule: the erythrocyte--its biology, chemistry, and functional variations. AB - Red blood cells were first observed in the mid-1600s and termed ruddy globules for their conspicuous shape and color. Since that time, the functional significance of this extraordinary membranous pouch of proteins and electrolytes has been carefully detailed. The architecture of the red blood cell, the biochemistry of hemoglobin, the mechanics of the oxygen-hemoglobin affinity altering diphosphoglycerate compounds, and the variants of hemoglobin are reviewed. Far from being a simple transport vehicle of oxygen to and from tissues, the red blood cell is a multifunctional entity whose absence would make life as we know it impossible. PMID- 11759132 TI - Anesthetists and the criminal law. PMID- 11759133 TI - Capsule history of the AANA journal. AB - This is a review of the history of the AANA Journal and its predecessor publications, the Bulletin of the National Association of Nurse Anesthetists, the Bulletin of the American Association of Nurse Anesthetists, and the Journal of the American Association of Nurse Anesthetists. PMID- 11759134 TI - Reducing anxiety in parents before and during pediatric anesthesia induction. AB - Fear and anxiety in a child undergoing surgery are correlated positively with the parent's level of anxiety, and interventions to decrease the parent's anxiety are appropriate. The purpose of this study was to determine whether viewing a video of an actual pediatric inhalation induction would reduce the level of parental anxiety. Eighty patients requiring an inhalation anesthetic induction were selected and randomized to 2 groups. Parents in the experimental group (group 1; n = 40) viewed a video demonstrating pediatric mask induction. Parents in the control group (group 2; n = 40) received an information pamphlet only. Anxiety was measured perioperatively in the parents and their children. Mean arterial pressure for children in group 1 was significantly lower during preoperative holding and following induction (P < .05). The level of anxiety postoperatively of children and parents in group 1 was significantly lower than that of children and parents in group 2 (P < .05). Viewing a preoperative video seems to be beneficial. Decreasing the parent's level of anxiety preoperatively may have a positive effect on the child's level of anxiety expressed postoperatively. PMID- 11759135 TI - Evaluation of word associations as a reliable postoperative indicator of implicit memory formation during the intraoperative period. AB - Patients expect to receive an anesthetic that prevents the formation of memories during the intraoperative period. Unfortunately, explicit memory formation occurs 40,000 times per year in the United States, while the incidence of implicit memory is thought to be greater. The purpose of the study was to evaluate the effectiveness of word associations as a reliable postoperative indicator of implicit memory formation during the intraoperative period. Forty-eight participants scheduled to undergo general anesthesia for an elective procedure were selected. During the administration of 0.77 +/- .18 microgram/kg per minute of remifentanyl and 0.31 +/- .04 end-tidal volume percent of sevoflurane in air/oxygen, word associations in the form of "Trivial Pursuit" (Hasbro, Inc, Pawtucket, RI) game statements were presented via headphones. Within 24 hours of surgery, each participant was given a postoperative word association test that included the experimental and control word associations. No reports of explicit memory were noted. The experimental word associations were correctly answered 19.3% of the time, while the control word associations were correctly answered 12.8% of the time (P = .014). The findings illustrated that the word association test in the form of Trivial Pursuit game statements/answers may serve as a reliable postoperative indicator of implicit memory formation during the intraoperative period. PMID- 11759136 TI - Military and civilian penetrating eye trauma: anesthetic implications. AB - In 20th century warfare, wounds from fragmentation weapons have become the number 1 cause of military hospital admissions during combat. Specifically, grenades, landmines, mortars, and artillery weapons have replaced guns and bullets. Consequently, penetrating eye injuries and maxillofacial injuries in the military have escalated dramatically. In the civilian sector, pipe bombs, explosive bottles used in gang warfare, and terrorist bombs, which are all fragmentation weapons, have generated new studies in the care of patients with penetrating eye injury. This change in the wounding pattern is, documented internationally in military-medical literature and in civilian-medical literature of relief agencies such as the International Committee of the Red Cross and the Red Crescent. The anesthetic management of open eye injuries has been a running controversy for 40 years in terms of the use of muscle relaxants. Nondepolarizing agents carry the risk of aspiration and increased intraocular pressure when trauma patients are intubated prematurely during rapid-sequence induction for "full stomachs." Succinylcholine would be the logical relaxant of choice for a rapid-sequence induction, but succinylcholine raises intraocular pressure. In many cases, the literature specifically contraindicates succinylcholine in the open eye injury for fear of extruding the content of the eye. A review of the vital assessment for the patient with a penetrating eye injury, as well as a comparative analysis of the literature, is presented. The conclusion favors pretreatment with a nondepolarizing agent and the use of succinylcholine during rapid-sequence induction. The eye injury itself is not the primary concern of this article. The primary concern is that open eye injuries serve as hallmarks for for more dangerous injuries. Penetrating open eye injuries merit extensive clinical assessment that can be life saving. PMID- 11759138 TI - The prevalence of visible and/or occult blood on anesthesia and monitoring equipment. AB - The Occupational Safety and Health Administration (OSHA) and the Centers for Disease Control and Prevention (CDC) have attempted to stop the spread of blood borne pathogens by issuing several recommendations and regulations. However, unless healthcare workers comply with these standards, they are not effective. In the anesthesia care environment, the anesthetist is responsible for ensuring that the equipment is clean, and disinfected, before use. We studied the prevalence of visible and occult blood on 6 types of anesthesia and monitoring equipment identified as ready for use in 28 operating suites, in 2 facilities. The sample consisted of 336 observations of the 6 types of equipment. The equipment was inspected for visible blood and then tested for occult blood using a 3-stage phenolphthalein test. Of the 336 observations, 110 (32.7%), were positive for occult blood with only 6 showing visible blood. The presence of blood on this equipment may be in direct violation of the OSHA Blood-borne Pathogen Standard and the infection control guidelines of the American Association of Nurse Anesthetists. Furthermore, the presence of blood on this equipment may increase the risk for nosocomial and occupational exposure to viral and bacterial pathogens. Recommendations were made to decrease the risks from this contamination by redesigning equipment, increasing the use of disposable equipment, and ensuring compliance with effective infection control practices. PMID- 11759137 TI - Prevention of vomiting after general anesthesia for pediatric ophthalmic surgery. AB - We evaluated the effectiveness of a multifaceted general anesthesia protocol designed to minimize postoperative vomiting after pediatric eye surgery. A convenience sample of 150 consecutive children, aged 2 weeks to 18 years, who received general anesthesia for pediatric ophthalmic surgery was studied. General anesthesia was administered with induction by mask for 82.7% of the children and intravenously using propofol in 17.3% of the children. Anesthesia was maintained using halothane or isoflurane, oxygen, and air mixture for all patients. Morphine sulfate was used for additional pain relief, up to 0.1 mg/kg. Gastric aspiration was performed after intubation for each child. Metoclopramide, 0.15 mg/kg, and 0.1 mg/kg of ondansetron were administered before the end of each operation. Postoperatively, patients were monitored for vomiting for 24 hours. Postoperative vomiting occurred in 11 (7.3%) of 150 cases. Acute elevation of intraocular pressure was found in 5 of the 11 children who vomited. This vomiting was unresponsive to intravenous rescue ondansetron, but responded to lowering the intraocular pressure. The incidence of postoperative vomiting after general anesthesia for pediatric eye surgery can be substantially decreased by adopting a protocol designed to lessen the emetic effects of general anesthesia. Limited use of nitrous oxide for mask induction only, gastric emptying, and administration of metoclopramide and ondansetron intravenously in combination proved effective in reducing the incidence of postoperative vomiting. PMID- 11759139 TI - Anesthetic implications of a partial molar pregnancy and associated complications. AB - In the United States, molar pregnancy occurs between 1 in 1,200 and 1 in 2,500 pregnancies. The critical nature of complications associated with a molar pregnancy requires advanced perioperative anesthetic management. This case report details the perioperative events of a 34-year-old gravida 5, para 3, with a partial molar pregnancy who underwent general anesthesia for a dilatation and curettage procedure, following therapeutic termination of a coexisting fetus at 18 weeks' gestation. Her initial presentation, anesthetic and operative management, and postoperative course are described clearly. The medical and anesthetic interventions required for treatment of molar pregnancy are reviewed. Of molar pregnancies, 80% are uncomplicated and follow an unremarkable course. However, for the remaining 20%, complications can be severe and may lead to substantial morbidity and mortality in otherwise healthy women. PMID- 11759140 TI - A comparison of motor block between ropivacaine and bupivacaine for continuous labor epidural analgesia. AB - The aim of the present study was to compare the amount of motor block produced by different loading doses of ropivacaine and bupivacaine when delivered in a dilute solution with added opioid. Sixty-eight healthy term primigravid parturients were randomized to receive an initial bolus dose of 10 mL of 1 of the following: 0.25% bupivacaine (high bupivacaine), 0.25% ropivacaine (high ropivacaine), 0.125% bupivacaine (low bupivacaine), or 0.125% ropivacaine (low ropivacaine). Each loading dose had 10 micrograms of sufentanil added to it. All groups received a continuous infusion of a 0.1% study drug infusion with 0.6 microgram/mL of sufentanil at a rate of 8 to 14 mL/h to maintain analgesia. Supplemental doses of 10 mL of a 0.125% study solution with 10 micrograms of sufentanil were given as needed. Pain scores and a modified Bromage scale were used to assess analgesia and motor block. A statistically significant greater percentage of parturients receiving bupivacaine had motor block than those who received ropivacaine, with a marked decrease in the occurrence of motor block in the low ropivacaine group. The pain relief seemed to be less satisfactory in the ropivacaine groups, but the difference was not statistically significant. Ropivacaine produced significantly less motor block than bupivacaine in the 0.25% and the 0.125% loading doses, with the greatest difference seen in the lower concentration loading dose of ropivacaine. PMID- 11759141 TI - Update for nurse anesthetists. Part 6. Full-body patient simulation technology: gaining experience using a malignant hyperthermia model. AB - Simulation technology is extremely useful for training workers in a variety of industries. Simulation concepts have been developed and refined in full-body patient simulators. Contemporary full-body patient simulators can be used to teach the essential concepts of many healthcare professions, and they offer practice dealing with critical events, concentrating on the thought and decision making processes related to favorable patient outcomes. Full-body patient simulators provide practitioners the opportunity to manage realistic and advanced physical findings in a variety of areas and are capable of responding to a large number of pharmacologic agents and a host of clinical interventions. The ability to combine high-fidelity educational tools with both classroom lecture and clinical experience provides nurse anesthetists the opportunity for a unique experience in a highly controlled and safe environment. Numerous technological and educational advantages and the chance for hands-on assessment and treatment of some of anesthesia's rarest and most life-threatening events provide a one-of a-kind educational session for CRNAs. PMID- 11759142 TI - The addition of interscalene block to general anesthesia for patients undergoing open shoulder procedures. AB - Several studies have demonstrated that interscalene brachial plexus anesthesia alone decreases postoperative pain, nausea, vomiting, urinary retention, and unplanned hospital admissions compared with general anesthesia alone. Anecdotal evidence suggests that an interscalene block combined with general anesthesia decreases unwanted effects of general anesthesia following open shoulder surgery. We compared the effect of combined interscalene block and general anesthesia with general anesthesia alone on Aldrete scores, length of postanesthesia care unit (PACU) stay, verbal rating scale (VRS) pain scores, incidence of postoperative narcotic administration and nausea, and patient satisfaction in a convenience sample of 52 men and women, ASA physical status I, II, or III. Group 1 received standard general anesthesia alone. Group 2 received an interscalene block in combination with general anesthesia using a standard technique. Group 2 had significantly lower VRS scores than group 1 while in the PACU, on the day of surgery, and on postoperative days 1 and 2. Overall satisfaction with the anesthetic technique was higher in the group 2 than in group 1. Results suggest that adding an interscalene block to general anesthesia can be of value in today's outpatient-dominated surgery schedule. PMID- 11759143 TI - Cost analysis in vitrectomy: monitored anesthesia care and general anesthesia. AB - A retrospective study was performed to compare differences in hospital charges between monitored anesthesia care with retrobulbar block and general anesthesia among patients having vitrectomy. Of 128 consecutive patients undergoing vitrectomy between July 1996 and July 1997, group 1 received general anesthesia (n = 41), group 2 received monitored care anesthesia with retrobulbar block (n = 59), and 28 patients were eliminated from the study. There were significant differences in anesthesia charges, operating room charges, pharmacy charges, and total hospital charges between groups 1 and 2. Charges associated with monitored care anesthesia with retrobulbar block are 20% less than charges associated with general anesthesia. Fewer patients in group 2 required postoperative intravenous narcotics than in group 1. PMID- 11759144 TI - Anesthetic implications in epidermolysis bullosa dystrophica. AB - Epidermolysis bullosa is a genetic mechanobullous disease of the stratified squamous keratinizing epithelium that affects the skin and mucous membranes. Its primary feature is the formation of blisters after minor shearing trauma to the skin or mucous membranes that can result in debilitating, even life-threatening scarring. The disease presents special problems for the anesthesia provider because the equipment used to deliver anesthesia and monitor vital signs may cause serious postoperative complications. The challenge is to maintain patency of the airway and use monitoring technology without damaging epithelial surfaces, which could result in permanent scarring. Successful anesthetic management of a patient with epidermolysis bullosa is possible if precautions with anesthetic instrumentation are observed. PMID- 11759145 TI - Relative value guide basic units in operating room scheduling to ensure compliance with anesthesia group policies for surgical procedures performed at each anesthetizing location. AB - Many anesthesia groups provide services in a spectrum of anesthetizing locations, including offices, free-standing ambulatory surgery centers, diagnostic clinics, and traditional hospital operating rooms. The use of a uniformly understood measure of case complexity could assist an anesthesia group in ensuring appropriate anesthesia provider expertise and equipment availability at each anesthetizing location. In this article, we show how the American Society of Anesthesiologists' Relative Value Guide (ASA RVG) basic units can be used as a criterion to establish the maximum level of complexity of cases performed at each location by an anesthesia group. By reviewing ASA RVG basic units at several anesthetizing locations in lowa, we found that ASA RVG basic units differ among sites. The ASA RVG basic units can be used to identify cases that are seemingly unexpected for an anesthetizing location. There are several reasonable values that an anesthesia group can use for its maximum number of basic units at an anesthetizing location. PMID- 11759146 TI - Update for nurse anesthetists. Patr 1. The hazards of surgical smoke. AB - Inhaling surgical smoke is an ever-growing concern since the majority of all surgeries generate laser or electrosurgical smoke. Anesthesia providers must understand the dangers of surgical smoke and how to control or minimize exposure. This Journal course explores the hazards of surgical smoke (including plume odor, particulate matter size, viability of the smoke contents, and laparoscopic concerns) by citing significant research studies that support the threats and potential threats associated with surgical smoke. Effective methods to evacuate this plume are described to protect not only the healthcare professional but also the patient. Surgical smoke will continue to cause problems and concerns unless the surgical team is committed to providing a safe environment through appropriate and diligent smoke evacuation methods. PMID- 11759147 TI - Conflict for the court. PMID- 11759148 TI - [New molecules]. AB - Presentation of six drugs: clopidogrel, raloxifene, mecillinam, natiglinide and repaglinide, pneumococcal conjugate vaccine. For each, positive and negative arguments, questions on hold and rating. PMID- 11759149 TI - [Medical use of cannabis through history]. PMID- 11759150 TI - [Chocolate, an ancient remedy still enjoyed today]. PMID- 11759151 TI - [Medieval pharmacopoeias, images and manuscripts]. PMID- 11759152 TI - Toxicological evaluation of nitrosamines in condoms. AB - Volatile N-nitrosamines have been found in rubber products including gloves, balloons, toys, baby bottle teats, soothers, and condoms. N-Nitrosamines are potent carcinogens, and therefore, European legislation has limited the release of N-nitrosamines and N-nitrosatable compounds in teats and soothers to 0.01-0.1 mg/kg rubber, respectively. Previously, endogenous nitrosamine formation in the vagina has been suggested as a cause of cervical cancer. It was speculated that exogenous N-nitrosamines and N-nitrosatable compounds from condoms may also lead to genital cancer. Therefore, we reviewed the literature and calculated the risk for the induction of tumors by nitrosamines from condoms. In vitro Biaudet et al. (1997) found up to 88 ng nitrosatable compounds migrating from condoms to cervical mucous within 24 hrs. During sexual intercourse about 0.6 ng may migrate in the female genital mucous membranes because of the short contact to the condom, e.g. 10 min. Comparable amounts of nitrosamines may also migrate in the penile skin. Estimating 1500 contacts to condoms during lifetime (50 condoms/year for 30 years) this may result in the adsorption of up to 0.9 microgram nitrosamines in total. Animal studies in Syrian hamsters showed the induction of local and/or systemic tumors, in particular liver tumors, after topical application of nitrosamines to the skin or mucous membrane at a total dose of about 1 g. This dose exceeds the dose to be expected from contact with condoms by more than 1 million. Also, epidemiological studies do not support a role for condoms in the induction of cancer. The incidence of cervical cancer and liver tumors is high in developing countries, where condoms are seldom used. In addition, humans are regularly exposed to nitrosamines from food and tobacco smoke at a dose which is 1,000 to 10,000 fold higher than expected from condom use. In summary, the risk for the induction of tumors from nitrosamines in condoms is very low. PMID- 11759153 TI - Detection of microbial volatile organic compounds (MVOCs) produced by moulds on various materials. AB - Twelve fungal species were screened for microbial volatile organic compounds (MVOCs): Aspergillus fumigatus, A. versicolor, A. niger, A. ochraceus, Trichoderma harzianum, T. pseudokoningii, Penicillium brevicompactum, P. chrysogenum, P. claviforme, P. expansum, Fusarium solani and Mucor sp. More than 150 volatile substances derived from fungal cultures have been analysed by head space solid-phase microextraction (HS-SPME). Each species had a defined MVOC profile which may be subjected to considerable modification in response to external factors such as cultivation on different substrata. The cultivation on different substrata changes the number and concentration of MVOCs. Species specific volatiles may serve as marker compounds for the selective detection of fungal species in indoor environments. Examination of MVOCs from indoor air samples may become an important method in indoor air hygiene for the detection of type and intensity of masked contamination by moulds. PMID- 11759154 TI - Hand disinfection according to the European Standard EN 1500 (hygienic handrub): a study with gram-negative and gram-positive test organisms. AB - It was the aim of this study to compare the efficacy of alcohol-based hand disinfectants according to European Standard EN 1500 (hygienic handrub), using the routine test organism Escherichia coli and, additionally, Micrococcus luteus as a surrogate for Gram-positive pathogens. One ethanol-based hand disinfectant (product A) and one propanol-based hand disinfectant (product B) were used in all experiments. Product B (propanol-based) was significantly more effective against both test organisms than product A (ethanol-based) in quantitative suspension tests but not in tests simulating practical conditions. In the experiments according to EN 1500 germ reduction rates obtained with the ethanol-containing formulation A were identical for E. coli and M. luteus. Product B was slightly, but not significantly more effective against M. luteus. To conclude, using E. coli as the test organism for evaluating the antibacterial efficacy of alcoholic hand disinfectants under practical conditions even appears to be sufficient to permit the drawing of conclusions for Gram-positive pathogens. However, more alcohol-based hand disinfectants should be tested in further studies to verify the results obtained. PMID- 11759155 TI - Comparison of different methods for the isolation of Burkholderia cepacia DNA from pure cultures and waste water. AB - DNA from Burkholderia cepacia was prepared from suspensions of pure cultures and artificially contaminated waste water. The efficacy of four standard methods (lysis buffer containing proteinase K, phenol/chloroform/isoamylalcohol extraction, microwave treatment, heat treatment) and six commercially available kits (Puregene, High Pure PCR Template Preparation Kit, InstaGene, QIAamp Tissue Kit, DNAzol, Elu-Quik) was compared in terms of sensitivity in a subsequent PCR. The results showed that a simple and inexpensive procedure using a lysis buffer containing proteinase K was superior to all other methods tested. PMID- 11759156 TI - Multinucleated giant cell appearance after whole body microwave irradiation of rats. AB - Multinucleated giant cells are common for some chronic inflammatory processes in the lung. These cells are formed by fusion of macrophages, but how the process relates to the kinetics of alveolar macrophage generation is not clear. This study investigated the influence of 2450 MHz microwave irradiation on alveolar macrophage kinetics and formation of multinucleated giant cells after whole body irradiation of rats. The range of electromagnetic radiation was selected as 2450 MHz microwaves at a power density of 5-15 mW/cm2. A group of experimental animals was divided in four subgroups that received 2, 8, 13 and 22 irradiation treatments of two hours each. The animals were killed on experimental days 1, 8, 16, and 30. Free lung cell population was obtained by bronchoalveolar lavage. Cell response to the selected irradiation level was followed quantitatively, qualitatively and morphologically using standard laboratory methods. Total cell number retrieved by lavage slightly decreased in treated animals showing time- and dose-dependence. Cell viability did not significantly change in the irradiated animal group (G2) as compared with the control group (G1). Multinucleated cells significantly increased (p < 0.01) in treated animals. The elevation of the number of nuclei per cell was time- and dose-dependent. Macrophages with two nucleoli were more common in animals treated twice or eight times. Polynucleation, that is three and more nucleoli in a single cell, was frequently observed after 13 or 22 treatments. Binucleation and multinucleation of alveolar macrophages were sensitive time- and dose-dependent morphological indicators of pulmonary stress. PMID- 11759157 TI - Capability of mucoid Pseudomonas aeruginosa to survive in chlorinated water. AB - Mucoid strains of Pseudomonas aeruginosa are characterized by an overproduction of the extracellular polysaccharide alginate. When suspended into chlorinated swimming-pool water or drinking water samples, mucoid bacteria revealed enhanced survival compared with isogenic nonmucoid cells. Removal of slime from mucoid bacteria abolished chlorine resistance, addition of purified alginate to washed bacteria again enhanced survival. Thus, alginate-containing slime confers protection on P. aeruginosa against chlorine and may contribute to survival of these bacteria in chlorinated water systems. PMID- 11759158 TI - Spatial impact of the Oder river plume on water quality along the south-western Baltic coast. AB - The Oder (Odra) river is the most important nutrient source and pollutant for the south-western Baltic Sea. Adjacent German-Polish coastal waters, the Oder (Szczecin) Lagoon and the Oder (Pomeranian) Bight therefore suffer from severe eutrophication and water quality problems. At the same time, summer (bathing) tourism is the most important economical factor in this coastal zone, especially on the islands of Usedom and Wolin. On the basis of model simulations and remote sensing data we analysed the spatial extent and variability of the Oder river plume in the lagoon and the Balic Sea in common summer situations and during the extreme Oder flood in August 1997. Water quality shows pronounced gradients between coastal waters and open Baltic Sea. In the lagoon, it usually takes more than 6 weeks until Oder water enters the large western bay, the Kleines Haff. During transport, degradation, transformation and sedimentation processes alter the water quality and prevent the inner coast of Usedom from direct impact of polluted Oder water. Ongoing nutrient supply promotes intensive algal proliferation in all parts of the lagoon and contributes to the low water transparency. Oder water passing the lagoon and entering the Baltic Sea is transported over long distances in narrow bands along the shore. Under easterly winds the water quality near well-known spas on Usedom is reduced due to Oder river plume impact. Upwelling effects can have negative impact on water quality, too. Intensive blooms of potentially toxic blue-green algae species, are the rule in the lagoon and frequent in the Oder Bight in summer. They are a hazard and limit the acceptance of swimming beaches at the inner coast of Usedom. Practical consequences of variable water quality gradients e.g. on hygienic water sampling are discussed. PMID- 11759159 TI - "Electro-fishing" in the lab: a new method to detect acute effects of heavy metals and organic pollutants in invertebrate indicator organisms. AB - Acute toxicity of heavy metals and organic pollutants was examined using Rhabditis oxycerca (Nematoda) and Paramecium spec. (Protozoa, Ciliata) as indicator organisms. The substances tested were based on the composition found in the river Odra. They were used in graduated dilution series (1000-fold, 500-, 250 , 167-, 125-, 100-, and 83-fold of the Odra concentration). In a special apparatus with an electric field the animals were induced to migrate from the anode to the cathode. Their migration activity (distance) and the number of migrating animals were influenced by the substances tested. To assess the extent of damage, results were compared with controls (tap water) and reference substances (aldicarb and chloracetamide). The investigations showed that heavy metal concentrations > 100-fold of the Odra concentration led to behavioural changes of both test organisms. The organic pollutants, in contrast, did not cause detectable changes in ciliates and only led to slight reductions in the migration activity of nematodes, without concentration-dependent gradations. PMID- 11759160 TI - Relationships between blood lead concentrations, intelligence, and academic achievement of Saudi Arabian schoolgirls. AB - This cross-sectional study examined the association between blood lead levels and neuropsychological and behavioural problems of 533 schoolgirls (6-12 years of age) who attended public schools in Riyadh, Capital of Saudi Arabia. Regression models were used to determine the best predictors of Beery VMI Saudi-based standard scores, TONI Saudi-based scores and rank percentile. The mean blood lead level was 8.11 +/- 3.50 micrograms/dl in the range of 2.3 to 27.36 micrograms/dl. Significant negative associations were noted between blood lead levels and Beery VMI Saudi-based standard scores as well as rank percentile. Lead had no effect on TONI Saudi-based standard scores. Beery VMI Saudi-based standard scores, TONI Saudi-based standard scores and rank percentiles were inversely related to pupils with blood lead levels > 9 micrograms/dl. These findings attest an association between neuropsychological and behavioural impairment and lead exposure at blood lead levels in the range of 9.02 to 27.36 micrograms/dl. The results of this study should be seriously considered by public health authorities to give more attention to this pediatric health problem. PMID- 11759161 TI - Biological monitoring of exposure of the general population to the organophosphorus pesticides chlorpyrifos and chlorpyrifos-methyl by determination of their specific metabolite 3,5,6-trichloro-2-pyridinol. AB - In this study we determined the concentrations of 3,5,6-trichloro-2-pyridinol (TCPyr) in urine samples from the general population. TCPyr is a specific metabolite of the organophosphorus pesticides chlorpyrifos and chlorpyrifos methyl. By the introduction of a new sensitive analytical method a limit of quantification (LOQ) of 0.1 microgram per litre urine could be achieved, a tenfold improvement of recent methods. Extraction of TCPyr from the urine and the clean up process were carried out by automatic steam distillation. Separation and quantitative analysis were performed using capillary gas chromatography and mass selective detection in selected ion monitoring mode. The excretion of TCPyr was studied by analysing spontaneous urine samples from 5 women and 45 men between the ages of 22 and 57 (median: 40 years) living in Mecklenburg-Vorpommern (Germany) who were not occupationally exposed to organophosporus pesticides. TCPyr was detected in all specimens and the concentrations were quantified. The median excretion was 1.4 micrograms/l (range: 0.12 to 124.8 micrograms/l), the 95th percentile 11.3 micrograms/l. Under the worst case assumption that all TCPyr measured in urine originated from the intake of intact pesticides and not (less toxic) breakdown products, a TCPyr concentration of 1.4 micrograms/l urine corresponds to a daily intake of approximately 2.5 micrograms chlorpyrifos/chlorpyrifos-methyl. The intake at the 95th percentile would be about 23 micrograms chlorpyrifos/chlorpyrifos-methyl per day. According to FAO/WHO the acceptable daily intake (ADI) is 10 micrograms per kg bodyweight and day for both chlorpyrifos and chlorpyrifos-methyl. PMID- 11759162 TI - Cytokines detectable in saliva of children as appropriate markers of local immunity of the oral cavity--an approach for the use in air pollution studies. AB - The objective of this study was the detection of proinflammatory markers in saliva to be involved in local immunity of the oral cavity. Therefore saliva of 167 schoolchildren aged 8-10 years were investigated for the presence of interleukin-8 (IL-8), tumour necrosis factor alpha (TNF alpha) and soluble tumour necrosis factor receptor type II (sTNFRII). In saliva of schoolchildren sufficient quantities of IL-8 (302.3-4208.6 pg/ml), TNF alpha (0.3-40.6 pg/ml) and sTNFRII (17.6-931.3 pg/ml) were detectable. IL-8, TNF alpha and sTNFRII revealed significant correlations with each other. Results suggest an immunoregulatory mechanism of IL-8, TNF alpha and TNF-receptor to be of special concern in host defence as well as in maintaining homeostasis of local immunity within the oral cavity. Saliva provides an ideal medium for the detection of proinflammatory markers of the oral cavity with respect to mucosal and granulotype origin and may be employed in air pollution epidemiology, especially with regard to children. PMID- 11759163 TI - Molecular detection of Campylobacter spp. in drinking, recreational and environmental water supplies. AB - A molecular detection assay was performed on 207 samples of drinking, recreational and environmental waters collected in Northern Ireland. The water sources which were PCR positive for Campylobacter spp. included 2/91 (2.2%) drinking water from domestic household taps, 5/57 (8.8%) swimming pool water, 1/23 (4.3%) lake water and 1/1 water from a jacuzzi. Extracted DNA from all water samples was amplified employing a sequence-specific PCR assay based on a 206 bp conserved region of the flagellin A-flagellin B (flaA/flaB) loci for Campylobacter jejuni, C. coli and C. lari. Given the physiological and cultural fragile nature of these species, no waters were cultured using conventional methods due to concern for reversion to non-culturability from time of collection to laboratory analysis. As this genus has been demonstrated to form a 'viable but non-culturable' (VBNC) form, failure to culture organisms conventionally from water does not necessarily equate to a negative result, hence molecular detection assays, especially those which can demonstrate cell viability, may be useful in helping to elucidate potential epidemiological sources and reservoirs of this organism, especially where water is suspected as being the vehicle of transmission. PMID- 11759164 TI - Successful PCR amplification of genomic DNA from Cryptosporidium parvum oocysts extracted from a human faecal sample: a rapid and simple method suited for outbreak analysis. AB - A method to extract genomic DNA from oocysts of Cryptosporidium parvum in human faecal material was developed and consisted of a simple alkali wash, freeze/boil technique. This method was simple, quick, sensitive, inexpensive and resulted in the production of genomic DNA which was free of PCR inhibitors and as such was a suitable template for the detection of C. parvum by various PCR amplification targets. PMID- 11759165 TI - Trends in social, political and technological impact factors of hygienic risks in German households. AB - This paper considers actual German trends of impact factors contributing to hygienic risks in domestic settings: Have there been or are there still alterations which may be relevant and which should have consequences for hygiene behavior? How is hygiene consciousness organized in the German society? Each of the alterations of hygiene determinants described below may appear to be marginal when looked at separately, thus disregarding any relationship to hygiene. However, as a whole to anticipate the conclusion they have clearly altered the hygiene risks in the household; some risks have decreased but others have grown worse. The author intends to initiate an objective discussion on home hygiene in Germany. The intention is not creating a sterile environment in the home but to realize the "hot spots" of hygiene in modern domestic settings in order to develop a targeted hygiene. PMID- 11759166 TI - Acceptable risk of environmental air pollution. PMID- 11759167 TI - Use of biomarkers in risk assessment. AB - The systematic development and application of biomarkers in environmental health risk assessment is a relatively new field. At first, the major interest was in biomarkers of exposure, borrowing concepts from pharmacology, then it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. While these markers provide evidence of exposures, they do not provide evidence of that toxicological damage has occurred. For this reason, measurements of DNA adducts and protein adducts are of interest, since they may provide bridges between exposures and disease end-points. In parallel, more quantitative and more sensitive end-points for diseases have been sought. Again, with advancing techniques in cytogenetics, extensive studies were conducted on such markers as chromosomal aberrations, micronuclei and other changes deemed to represent genomic damage. However, these types of end-points are quite unspecific for application to new hazards of uncertain human toxic (carcinogenic) potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced mechanistic insight. The advances in molecular genetics have led to an upsurge in interest in most susceptibility factors, and identification of polymorphisms of various enzymes has become possible. Ongoing search for "ultra high risk" individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a small differential risk, however theoretically or mechanistically important, offer only little practical use. PMID- 11759168 TI - Synthesis and antifungal activity of 3,3'-ethylenebis(5-alkyl-1,3,5-thiadiazine-2 thiones). AB - In a search for promising antifungal compounds, nine new 3,3'-ethylenebis(5-alkyl 1,3,5-thiadiazine-2-thiones) were synthesized by the reaction of ethylene diamine, carbon disulfide, formaldehyde, and the appropriate alkyl amine. The title compounds were tested for their antifungal activity in vitro against pathogenic (Trichophyton rubrum and Candida albicans), phytopathogenic (Penicillum expansum, Trichoderma hazianum, and Fasarium oxysporum), and aflatoxin producing (Aspergillus flavus) fungi. These compounds exhibited varied inhibitory effects on growth or sporulation of some tested fungal species. PMID- 11759169 TI - Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound. AB - In female B6D2F1 mice bearing an MXT-M-3,2 breast cancer graft the level of the phagocytic cells (e.g. of granulocytes and macrophages in the spleen and of granulocytes and monocytes in the blood) is significantly elevated. The positive correlation between the number of the phagocytic cells and the weight of the tumor indicates that the MXT-M-3,2 breast cancer promotes myelopoiesis, presumably by secretion of hematopoietic growth factors like GM-CSF. This process can be described for each phagocyte type by a regression equation. Due to its hormonal potency [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) (meso-1-PtCl2) can reduce the excessive numbers of the granulocytes and macrophages, which seem to be responsible for the progressive growth of the MXT-M-3,2 breast cancer. This process leads to an interruption of the vicious circle of mutual growth stimulation of breast cancer cells and these phagocytes. The target of meso-1-PtCl2 is the estrogen receptor (ER) of the breast cancer cell. The interaction between meso-1-PtCl2 and the ER presumably results in a diminished secretion of hematopoietic growth factors and hence in a decline of the number of phagocytic cells. Meso-1-PtCl2 does not inhibit the proliferation of tumor cells by direct interaction with their DNA, as is described for platinum complexes like cDDP. In its mode of action the equipotent, breast cancer inhibiting drug cDDP differs from meso-1-PtCl2. This is obvious from the fact that in cDDP--but not in meso-1-PtCl2-treated, tumor bearing mice the number of granulocytes and macrophages does not markedly deviate from that in untreated control mice with tumors of the same weight. The drug cDDP probably does not interfere with the mechanism of the secretion of hematopoietic growth factors. The reduction of the number of tumor cells by cDDP leads to a decline of the number of phagocytic cells in accordance with the respective regression equations. In contrast to meso-1-PtCl2 and cDDP, ovariectomy causes elevated phagocyte numbers, probably due to the strongly reduced estrogen level. The studies described in this publication indicate that the anti-breast cancer activity of meso-1-PtCl2 is caused by a decimation of phagocytes and with this by an abolition of the tumor promoting effect. Furthermore, a restoration of the natural immunosurveillance seems to be of importance. PMID- 11759170 TI - Naphthazarin derivatives (VIII): Synthesis, inhibitory effect on DNA topoisomerase-I, and antiproliferative activity of 6-(1-acyloxyalkyl)-5,8 dimethoxy-1,4-naphthoquinones. AB - 6-(1-Acyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinone (DMNQ; 5,8-dimethoxy-1,4 naphthoquinone) derivatives were synthesized and examined for their inhibitory effect on DNA topoisomerase-I (Topo I) and their antiproliferative activity against L1210 cells. The Topo-I inhibitory effect of 6-(1-hydroxyalkyl)-DMNQ derivatives was found to be dependent on the size of the alkyl chains, suggesting that lipophilicity might be one important factor influencing the inhibitory effect. It was found that acylation of 6-(1-hydroxyalkyl)-DMNQ derivatives possessing alkyl chains of C2-C5 enhanced both bioactivities, suggesting that an increase of electrophilicity in the quinoid moiety makes the electrophilic arylation of bionucleophiles more favorable. It is noteworthy that 6-(1 heptanoyloxyethyl)-DMNQ exhibited both the most potent Topo I inhibitory activity (IC50, 11.5 microM) and the greatest antiproliferative activity (ED50, 0.05 microM) upon L1210 cells. PMID- 11759171 TI - Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids. AB - In order to study the influence of the length of the amino acid chain of N,N phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, beta-alanine and gamma-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the beta-alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylene-tetrazole. The ED50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs. PMID- 11759172 TI - Antinociceptive properties of chalcones. Structure-activity relationships. AB - Eleven chalcones were prepared and tested as antinociceptive agents using the writhing test in mice. Some compounds, given intraperitoneally, caused potent and dose-related antinociception, being several times more active than some reference drugs. The results evidenced that some physico-chemical parameters are involved in the pharmacological activity. 3,4-Dichlorochalcone (2) was the most effective compound, and was also studied in another model of pain in mice, the formalin test. Here it inhibited only the inflammatory pain (second phase), being equipotent to the reference drugs. PMID- 11759173 TI - Industrial ecology: a new perspective on the future of the industrial system. AB - Industrial ecology? A surprising, intriguing expression that immediately draws our attention. The spontaneous reaction is that "industrial ecology" is a contradiction in terms, something of an oxymoron, like "obscure clarity" or "burning ice". Why this reflex? Probably because we are accustomed to considering the industrial system as isolated from the Biosphere, with factories and cities on one side and nature on the other, as well as the recurrent problem of trying to minimise th impact of the industrial system on what is "beyond" it: its surroundings, the "environment". As early as the 1950's, this end-of-pipe angle was the one adopted by ecologists, whose first serious studies focused on the consequences of the various forms of pollution on nature. In this perspective on the industrial system, human industrial activity as such remained outside the field of research. Industrial ecology explores the opposite assumption: The industrial system can be seen as a certain kind of ecosystem. After all, the industrial system, just as natural ecosystems, can be described as a particular distribution of materials, energy, and information flows. Furthermore, the entire industrial system relies on resources and services provided by the Biosphere, from which it cannot be dissociated. (It should be specified that "industrial", in the context of industrial ecology, refers to all human activities occurring within modern technological society. Thus, tourism, housing, medical services, transportation, agriculture, etc. are part of the industrial system.) Besides its rigorous scientific conceptual framework (scientific ecology), industrial ecology can also be seen as a practical approach to sustainability. It is an attempt to address the question, "How can the concept of sustainable development be made operational in an economically feasible way?" Industrial ecology represents precisely one of the paths that could provide concrete solutions. Governments have traditionally approached development and environmental issues in a fragmented and compartmentalised way. This is illustrated in the classical end-of pipe strategy for the treatment of pollution, which has proven to be quite useful, but not adequate to make an efficient use of limited resources, in the context of a growing population with increasing economic aspirations. Thus, industrial ecology emerges at a time when it is becoming increasingly clear that the traditional pollution treatment approach (end-of-pipe) is not only insufficient to solve environmental problems, but also too costly in the long run. PMID- 11759174 TI - Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. AB - It is only recently that folate deficiency has been implicated in the development of cancer. The mechanisms by which folate might protect against cancer are not clear but may relate to its role in DNA methylation and DNA synthesis. All case control, cohort and intervention trials reported in English, French, or German, on folate intake or blood levels in relation to the risk of colorectal, breast, and cervix cancer were reviewed. Twenty case-control, and 12 nested case-control or cohort studies were identified. The epidemiological studies consistently show an inverse association between intake and/or levels of folate and the frequency of colorectal carcinomas, and less clearly of adenomas. Long-term use of supplements of folate seems to be of greater benefit than dietary intake. The effect of folate seems to be modulated by alcohol, methionine, and MTHFR polymorphisms. Results from animal studies suggest that folate supplementation might decrease or increase cancer risk depending on dosage and timing. Recent studies also suggest an inverse association between folate intake and breast cancer among women who regularly consume alcohol. Conversely, epidemiological evidence remains uncertain for the role of folate in cervical cancer prevention; the results of two intervention trials on rates of cervical intraepithelial neoplasia regression or progression were negative. An effect of folate later in carcinogenesis is not supported by the few (nested) case-control studies on invasive cervical cancer. Some of the conflicting results may be due to the fact that dietary intake or blood levels of folate do not accurately reflect folate concentrations in the cells of cancer origin. Furthermore, only a few studies have taken into account the modulating effect of alcohol, methionine, and MTHFR polymorphisms in their analyses. The observed inverse associations between folate and risk of cancer, on the other hand, may be confounded by various factors, especially by other potentially protective constituents in fruits and vegetables. Ongoing intervention studies can strengthen evidence for causality by excluding such confounding, but the optimal dose, duration, and stage of carcinogenesis and the appropriate (genetically predisposed) study group for folate chemoprevention are not yet defined. PMID- 11759175 TI - Postoperative patterns and kinetics of cTnI, cTnT, CK-MB-activity and CK-activity after elective aortic valve replacement. AB - OBJECTIVES: The aim of this prospective study was to evaluate postoperative kinetics of four different biochemical ischaemic markers after elective aortic valve replacement (AVR). Additionally, pre-, peri- and postoperative data were analysed in order to identify factors with possible impact on the postoperative release of the selected enzymes. DESIGN: Forty patients (14 males, 26 females, aged 70 +/- 11 years; EF = 54 +/- 18% [mean +/- SD]) undergoing elective AVR were prospectively included in this study. For all patients, serum concentrations of cTnI, cTnT, and serum activities of CK-MB and CK were measured preoperatively as well as 0, 6, 12, 24, 48 and 120 hours after removal of the aortic cross-clamp. Clinical data were assessed in all patients and correlated with postoperative enzyme patterns. RESULTS: There were no major complications. Preoperatively, all patients showed enzyme values in the normal range whereas the four ischaemic markers reached higher values postoperatively. cTnI reached its maximum values 24 hours (XMed = 2.35 micrograms/L, 95%-CI [2.0, 3.3]) and cTnT 48 hours after the operation (XMed = 0.239 microgram/L, 95%-CI [0.174, 0.283]). Typical biphasic release kinetics could be demonstrated for cTnT. There was a high linear correlation between cTnI and cTnT at all sampling times. In contrast, a high linear correlation between cTnI, cTnT, and CK-MB-activity was only found 48 hours after aortic unclamping. cTnI nearly was in normal range 120 h postoperatively (XMed = 0.5 microgram/L, 95%-CI [0.2, 0.6]), whereas cTnT still remained pathologically elevated (XMed = 0.223 microgram/L, 95%-CI [0.137, 0.299]). No linear correlation was found between maximum values of the ischaemic markers postoperatively and age, gender, body surface area, ejection fraction, LV hypertrophy, operating time, ECC time, time of cardiac arrest, lowest body temperature, perfusion pressure, cardioplegia volume, reperfusion time, postoperative septiformic circulatory instability, or ventilation time. CONCLUSIONS: All four ischaemic markers showed individual peak characteristics and kinetics after uncomplicated AVR. In contrast to previous findings, aortic cross-clamping time had no detectable impact on postoperative peak patterns of any ischaemic marker. PMID- 11759176 TI - Febrile seizures and parental anxiety: does information help? AB - AIM OF THE STUDY: To investigate the effect of febrile seizures on the behaviour and emotional situation of parents in order to improve our attitude towards these children and parents in future. METHODS: We analysed 135 questionnaires on parents' behaviour and emotional situation during and after a febrile seizure in their children. RESULTS: Febrile seizures were unknown to 44% of the parents. 121 parents (91%) reported severe anxiety on witnessing the first febrile seizure. In 69% the anxiety was so strong, that the parents believed their child would die. Severe anxiety was significantly associated with lack of knowledge about febrile seizures: 79% (no knowledge of febrile seizures) versus 59% (with knowledge). The level of anxiety appeared to be associated with low educational level, but not with ethnic background or income. CONCLUSIONS: Our study shows that knowledge of febrile seizures among concerned parents in our region remains insufficient. The results are ambiguous. On the one hand we found an association between severe anxiety and lack of knowledge on febrile seizures, suggesting that information prior to the first febrile seizure might reduce the anxiety level and thus lead to appropriate reactions in case of recurrence. On the other hand although parents knew about febrile seizures, they still had very high anxiety levels and would react inappropriately in case of recurrence. Therefore if information is provided to parents, it must be specific, especially about which measures are to be taken or avoided respectively. A prospective study to observe positive and negative effects of preventive information is needed. PMID- 11759177 TI - Efficacy and safety of phospholipid liposomes in the treatment of neuropsychological disorders associated with the menopause: a double-blind, randomised, placebo-controlled study. AB - A double-blind, randomised, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of phospholipid liposomes (Liposom Forte) administered parenterally in the treatment of anxiety and depression linked to the menopause. A total of 64 females aged 40-60 years were randomised to receive the active drug or placebo intramuscularly; 58 patients completed the study. Treatment lasted 60 consecutive days. One i.m. administration of 2 ml active drug or placebo every other day was carried out. Efficacy was evaluated by the Hamilton Anxiety Scale (HAMA) and the Climacteric Index. An intention-to-treat analysis was performed, defined as all patients administered with at least one dose of the study medications with at least one return visit. A highly significant (p < 0.001) decrease in HAMA total score in both groups was noted. However, the decline in the HAMA score was significantly greater in patients administered phospholipid liposomes after 40 days (p = 0.006), 60 days of treatment (p < 0.001) and at the last follow-up visit (p < 0.001). Also, there were statistically significant differences between treatment groups after 60 days of therapy for individual items, such as anxious mood (p = 0.006), tension (p = 0.024) and fear (p = 0.009), with significantly less patients experiencing these symptoms in the phospholipid liposomes-treated group. When the Climacteric Index was evaluated, a highly significant (p < 0.001) decrease in the total score in both groups was noted. However, the decline was significantly greater in patients administered phospholipid liposomes after 40 days of treatment (p = 0.017), 60 days of treatment (p = 0.0013) and at the last follow-up visit (p = 0.0012). Significant differences between treatment groups were recorded after 60 days in asthenia (p = 0.05), dizziness (p = 0.024) and restlessness (p = 0.019) in favour of the active treatment. Twelve patients reported at least one adverse event, nine in the phospholipid liposomes group and three in the placebo group (p = 0.062). The most commonly reported event was drowsiness with two reports in each group. These findings further demonstrate that phospholipid liposomes administered intramuscularly are active against mild anxiety and depressive symptoms in menopausal women. PMID- 11759178 TI - Women's views on the introduction of Annual Screening Mammography to those aged 40-49 years (a pilot study). PMID- 11759179 TI - The effects of sublingual glyceryl trinitrate on walking distance in patients with intermittent claudication. A randomised, doubled-blind, placebo-controlled, cross-over study. AB - BACKGROUND: Intermittent claudication (IC) is a common problem in older age. New work shows that the administration of glyceryl trinitrate (GTN) can reduce the fall in ankle brachial pressure index (ABPI) after exercise and can increase maximum walking distance by 19% on treadmill exercise. The aim of this study was to further define the clinical benefits of GTN in patients with PVD. METHODS: The study is of a randomised, double-blind, placebo-controlled cross-over design. We studied 29 patients with intermittent claudication where the median age was 67.5 years (45-84). This included 20 males and nine females, and six of these patients were diabetics. To be selected, the patients had to have a history of IC with a resting ABPI of 1.0 or less, that fell by more than 0.1 on exercise. Patients were walked for 15 min on flat ground following GTN spray or placebo and total distances walked were measured. This was then followed by the crossover component of the trial. RESULTS: Median walking distance with placebo was 825 m (100-1300 m) and with GTN was 900 m (240-1400 m). This is an increase of 9% (p = 0.02, using the Wilcoxon matched pairs signed ranks test). CONCLUSION: This study shows a statistically significant improvement in walking distance with GTN in patients with IC. PMID- 11759180 TI - Recent advances in breast cancer (the 37th ASCO meeting, May 2001). AB - Data from phase III clinical trials suggest that high dose chemotherapy (HDC) is currently not indicated for any stage of breast cancer. Therefore HDC should only be considered within the context of clinical trials. Furthermore, there is no significant evidence to support the routine use of taxanes in women with metastatic breast cancer (MBC) and further research is required to address this issue. A well-designed randomised controlled trial has shown that expressive support psychosocial therapy does not improve survival of women with MBC. Her2 overexpression seems to be a significant predictor of response to taxanes and anthracyclines, and FISH testing for Her2 seems to be superior to IHC in predicting response to Herceptin. Recent evidence confirms the independent prognostic value of VEGF, UPA and PAI-1 in women with early breast cancer and suggests that such parameters may have a role in selecting systemic therapy. Biological therapy using inhibitors/antagonists of angiogenesis and EGFR seems to be safe and well tolerated. Although the response rates are currently unimpressive, further research using survival as an endpoint is required. PMID- 11759181 TI - Effect of bioflavonoids (trihydroxyethylrutin and disodium flavodate) in vitro on neutrophil reactive oxygen production and phagocytic ability assessed by flow cytometry. AB - Neutrophil granulocytes have been described as agents of defence and destruction. The effect of two flavonoid compounds (trihydroxyethylrutin and disodium flavodate) on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 5 mg/l, 50 mg/l and 100 mg/l. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by means of a CD16 phycoerythrin-conjugated mouse anti-human monoclonal antibody. In vitro trihydroxyethylrutin (THET) and disodium flavodate (DF) treatment reduced reactive oxygen production (DF at 5 mg/l--40%, at 50 mg/l- 71% and at 100 mg/l--82%; THET at 5 mg/l--53%, at 50 mg/l--88%, at 100 mg/l--93%; all p < 0.001). This was rapidly reversible after plasma exchange. Both flavonolds did not affect neutrophil phagocytic ability. We conclude that THET and DF could decrease oxidative tissue damage by neutrophils. A beneficial effect in peripheral vein disease could be anticipated from these results. PMID- 11759182 TI - Clinical evaluation of the trophic effect of polydeoxyribonucleotide (PDRN) in patients undergoing skin explants. A Pilot Study. AB - OBJECTIVE: The purpose of this double-blind, randomised, placebo-controlled study was to assess the effects of intramuscular and subcutaneous PDRN in favouring the wound-healing process in donor sites of grafts. METHODS: 26 adult patients of both sexes (15 males and 11 females; mean age: 68.2 +/- 16.1 years) subjected to skin explants due to plastic surgery were eligible to participate in this double blind, placebo-controlled study. Patients were randomly allocated into the PDRN group (14 subjects) or the placebo group (12 subjects). PDRN (5625 mg/vial) or placebo were administered by the intramuscular route once daily, associated with a subcutaneous administration of the same dosage form (2 vials every 3 days) for 10 consecutive days. The primary end point for efficacy was the evolution of wound healing in donor sites, which was evaluated measuring wound surface area and then calculating percentage re-epithelialisation. Secondary end points were local subjective symptoms, such as pain and itching, and objective signs such as perilesional erythema and blisters. Signs and symptoms were quantified through an analogue scale. RESULTS: At day 7 of the treatment period, the difference in percentage of re-epithelialisation was statistically significant (p < 0.008) in favour of the PDRN group. At the end of the observational period, between-group comparison demonstrated that patients treated with PDRN had a more prompt trophic effect. No adverse events were reported during the trial. CONCLUSIONS: The findings of our study demonstrated that PDRN is able to modify positively the repair processes in donor sites of autologous skin grafts. This could improve the clinical outcome and decrease the need for additional therapies or hospital stay. PMID- 11759183 TI - Cigarette smoking is independently associated with markers of endothelial dysfunction and hyperinsulinaemia in nondiabetic individuals with coronary artery disease. AB - BACKGROUND: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified. STUDY OBJECTIVES: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease. DESIGN: Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self reporting of smoking status together with plasma cotinine measurements. SETTING: Cardiology and cardiac surgery unit of a tertiary care referral centre. PATIENTS AND METHODS: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis. RESULTS: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001). CONCLUSIONS: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking. PMID- 11759184 TI - Tuberculous pericarditis: a report of three cases. AB - Three cases with the rare condition of tuberculous pericarditis are reported. PMID- 11759185 TI - Focus on ziprasidone. AB - Ziprasidone is a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The initial evidence suggests an effective dosage range of 80-160 mg/day. Clinical trials suggest that the drug is an effective antipsychotic in schizophrenia and schizoaffective disorder with a beneficial effect on negative symptoms and symptoms of depression. The main adverse effects appear to be somnolence (14%) and nausea (10%). Ziprasidone has relatively fewer side-effects and yet has at least equivalent efficacy for florid 'positive' symptoms compared with conventional antipsychotics. The additional serotonergic actions deliver further efficacy against 'negative' and affective symptoms of schizophrenia. Reduced effects on cognitive abilities compared to conventional antipsychotics make ziprasidone more attractive still. Barring any unforeseen complications, it appears to a most valuable addition to the antipsychotic agents. PMID- 11759186 TI - Patient and physician satisfaction with rofecoxib in osteoarthritis: results of the EVA (experience with VIOXX in arthritis) survey. AB - A nationwide survey was undertaken among 74,192 patients with osteoarthritis (OA) and 5986 physicians (including 5265 general practitioners [GPs]) in Belgium to evaluate satisfaction with the selective cyclo-oxygenase-2 inhibitor rofecoxib (12.5 or 25 mg, given once a day for an average of 30 days). Rofecoxib was considered by patients to be a very effective treatment for OA, with satisfaction scores of good or very good in the domains of pain, mobility and general satisfaction. More than 80% of GP-treated patients expressed a wish to continue rofecoxib therapy. Preference for rofecoxib was especially strong in patients (n = 45,453) who had previously been treated with conventional non-steroldal anti inflammatory drugs (NSAIDs), notably patients who had used diclofenac, ibuprofen and nimesulide. Physicians also expressed high satisfaction with rofecoxib, with more than 80% of surveyed physicians indicating a wish to continue prescribing the drug. The results of this large survey demonstrate a clear preference for rofecoxib over conventional NSAIDs in a substantial majority of OA patients. The satisfactory pain relief and excellent gastrointestinal safety profile of rofecoxib demonstrated in earlier controlled trials are likely to have been factors in patients' preferences for rofecoxib over NSAIDs. PMID- 11759187 TI - Postoperative altered plasma growth hormone levels--a predictor for postoperative complications? A case report. AB - We compared the onset of predictors for postoperative complications (lactate, total T2 (tT2), total T4 (tT4) and cortisone) retrospectively with the onset of altered growth hormone (GH) concentration in a patient who had had a lethal postoperative outcome and in 13 patients who were without postoperative complications for a period of 24 hours postoperatively. Compared with the values of the patients without postoperative complications, GH values were elevated (68 fold) 1 h after surgery to 103 ng/ml and lactate was increased (12-fold) to 12.7 mmol/l at 6 h postoperatively in the patient with the lethal outcome. The other parameters measured (tT3, tT4 and cortisone) showed no rapid alteration during the first hours postoperatively. This case report suggests that the rapid postoperative onset of raised GH concentration in plasma may be an earlier marker for postoperative complications than the 'established' predictors. PMID- 11759188 TI - The role of subareolar blue dye in identifying the sentinel node in patients with invasive breast cancer. PMID- 11759189 TI - Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy. AB - This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere. PMID- 11759190 TI - Facility profile. New women's hospital meets community needs. PMID- 11759191 TI - Energy saving strategies. Facilities cut costs by plugging into a variety of technical solutions. PMID- 11759192 TI - Healing by design. Eight key considerations for building therapeutic environments. PMID- 11759193 TI - Safe keeping. Some real-world advice on conducting a security assessment. PMID- 11759195 TI - All in the timing. Scheduling is key to floor care success. PMID- 11759194 TI - Decontamination details. Suggested considerations for hospital ED decon rooms. PMID- 11759196 TI - Measuring shortages of hospital nurses: how do you know a hospital with a nursing shortage when you see one? AB - Lack of clarity in definitions of shortages of hospital registered nurses may cause problems for effective policy making, particularly if different measures for identifying a nurse shortage lead to different conclusions about which hospitals and regions are experiencing a shortage. The authors compared different methods of identifying hospitals and regions with a shortage of registered nurses, including both relatively subjective measures (e.g., a hospital administrator's report of a nurse shortage) and more objective measures (e.g., number of registered nurses per inpatient year). Associations were strongest between self-reported shortage status and nursing vacancy rates and weaker for self-reported shortage status and registered nurses per inpatient year and overall regional supply of nurses. Different definitions of nursing shortage are not equally reliable in discriminating between hospitals and regions with and without nursing shortages. When faced with reports sounding an alarm about a hospital nursing shortage, policy makers should carefully consider the definition of shortage being used. PMID- 11759197 TI - A comparison of ambulatory care-sensitive hospital discharge rates for Medicaid HMO enrollees and nonenrollees. AB - With an increasing volume of Medicaid recipient enrollees in managed care, many states are developing tools for monitoring service quality and access of Medicaid recipients. This article explores the use of ambulatory care-sensitive (ACS) hospital discharge rates as a simple, practical indicator tool for monitoring the access of Medicaid health maintenance organization (HMO) enrollees through an empirical application in Massachusetts in 1995. Although unadjusted hospital discharge rates were lower, Medicaid HMO enrollees had higher age-gender-race adjusted total and ACS hospital discharge rates than Medicaid recipients enrolled in a primary care case management program under fee-for-service reimbursement. Higher HMO discharge rates for the specific ACS conditions of asthma and dehydration were suggestive of potential HMO access problems. PMID- 11759198 TI - Impact of HMO penetration and other environmental factors on hospital X inefficiency. AB - This study examined the impact of health maintenance organization (HMO) market penetration and other internal and external environmental factors on hospital X inefficiency in a national sample (N = 1,966) of urban U.S. hospitals in 1997. Stochastic frontier analysis, a frontier regression technique, was used to measure X-inefficiency and estimate parameters of the correlates of X inefficiency. Log-likelihood restriction tests were used to test a variety of assumptions about the empirical model that guided its selection. Average estimated X-inefficiency in study hospitals was 12.96 percent. Increases in managed care penetration, dependence on Medicare and Medicaid, membership in a multihospital system, and location in areas where competitive pressures and the pool of uncompensated care are greater were associated with less X-inefficiency. Not-for-profit ownership was associated with increased X-inefficiency. PMID- 11759199 TI - Selective contracting in managed care: the case of substance abuse treatment. AB - The authors address two critical questions concerning managed care and outpatient substance abuse treatment organizations. Specifically, they consider (1) to what extent selective contracting occurs between managed care firms and treatment providers and (2) what attributes of treatment providers and their operating environments are associated with selective contracting. Using data from a nationally representative sample of outpatient treatment organizations, the authors find evidence of systematic selection. Several indicators of providers' quality and costs, including accreditation status, private ownership, size, and prior experience with managed care, are positively associated with managed care contracting. By contrast, units providing methadone treatment are less likely to be involved in managed care. To a lesser extent, characteristics of treatment providers' operating environment, including extent of competition based on costs and attributes of the Medicaid managed care program, are also positively associated with managed care contracting. PMID- 11759200 TI - How much did the Medicaid expansions for children cost? An analysis of state Medicaid spending, 1984-1994. AB - The authors examine the relationship between the Medicaid eligibility expansions for children and state Medicaid spending during the period from 1984 to 1994. They find that the Medicaid expansions had relatively low incremental cost per enrollee--substantially below the average Medicaid expenditure for children. Expansion children tend to be older and have fewer disabilities. Moreover, many of the most expensive expansion children would have been covered by Medicaid medically-needy provisions had the expansions not occurred. The authors examine the implications of our findings for intensified Medicaid outreach efforts and for the State Children's Health Insurance Program. PMID- 11759201 TI - [Man and his genes]. PMID- 11759202 TI - Morphophysiological status of rat thyroid gland after subchronic exposure to low frequency electromagnetic field. AB - The objective of this study was to examine the impact of low-frequency electromagnetic field on male rat thyroid gland of Mill Hill strain. Animals were exposed to 50 Hz frequency, of decaying intensity from 500 microT to 50 microT and 10 V/m field, beginning 24 hours after birth, 7 hours a day, 5 days a week during three months. Results of histological and stereological analysis showed increased volume density of thyroid follicles, decreased thickness of the follicular epithelium, intrafollicular colloid content in lumen, decreased thyroid activation index, increased volume density of parafollicular cells, decreased volume of interfollicular connective tissue and increased number of degranulated mast cells in exposed animals in regard to control animals. Radioimmunologic assays were used to examine thyroid hormone concentrations in the blood serum revealing decrease of the total T4 as well as of total T3 in animals exposed to electromagnetic field in regard to controls. The obtained results show that a three month-exposition of animals to low frequency electromagnetic field led to morphofunctional alterations of the thyroid gland that can be referred to as reduced activity of the gland. PMID- 11759203 TI - [Association between HLA antigens and leukemia in the population of Vojvodina]. AB - INTRODUCTION: One of the most fascinating areas of research within the field of histocompatibility at present time concerns an observation that a major human histocompatibility system, HLA, is deeply involved in development of a great number of diseases. MATERIALS AND METHODS: HLA class I antigens were investigated in 225 cases with various kinds of leukemia: 112 patients with acute myeloblastic leukemia (AML), 31 with acute lymphoblastic leukemia (ALL), 44 with chronic myelocytic leukemia (CML) and 38 with chronic lymphocytic leukemia (CLL). Applying method of microlymphocytotoxicity, 13, 19 and 8 antisera were used for A, B and C loci respectively. Control group comprised 300 unrelated persons, whose phenotypic frequencies were used to calculate the relative risk (RR), while for values of RR greater than 1, we calculated etiologic fraction (EF), and for negative RR values we calculated preventive fraction (PF). RESULTS: Results of investigation showed that RR in AML was: for A2 = 1.144, for A3 = 1.038, for A29 = 1.814, for A34 = 2.69, for B7 = 1.06, for B14 = 1.74, for B17 = 1.65 and for B21 = 2.49 and B35 = 1.77 with value of chi 2 test of 4.62 and 4.63; that RR in ALL was: for A1 = 1.61, for A2 = 1.1, for A10 = 1.23, for A11 = 1.57, for A30 = 1.4, for A32 = 2.2, for B7 = 2.81 with value of chi 2 test 4.39; that RR in CML was: for A2 = 1.21, for A32 = 1.89, for B7 = 1.52, for B12 = 1.2 and for B15 = 3.28 with value of chi 2 test of 5.89; and that RR in CLL was: for A1 = 1.35 with value of chi 2 test of 3.973, RR for A2 = 1.02, for A28 = 1.97, for A32 = 1.25, for B5 = 1.44, for B8 = 1.27, for B13 = 1.91 without statistically significant differences of frequencies except for A1. Investigation of differences between haplotype frequencies among controls and patients showed statistically significant difference of A10 B40 haplotype in CML with RR value 7.24, while there were no statistically significant differences between controls and other leukemias. DISCUSSION: Our results of investigation showed statistically significant differences between HLA frequencies in the control group and investigated diseases, and that the relative risk is under 1, and values of chi 2 test under borderline values for B21 and B35 in AML, for B7 in ALL, for B15 in CML and for A1 in CLL. CONCLUSION: Results of this investigation point to an association between HLA system and leukemias. This association is of great importance because it provides a new tool for investigation of genetics and etiology of abovementioned diseases. PMID- 11759204 TI - [Classification of dysphonias based on the primary etiologic factor (part II)]. AB - INTRODUCTION: Phonation is a complex integral function of an organism. Regular phonation is characterized by: clearness and adequate pitch. Dysphonia is a disorder of phonation. It can have many acoustic forms, but hoarseness is the best known symptom of dysphonia. Acoustic phenomena in regard to voice are caused by: irregularities in vocal cord vibration, turbulent airflow in the glottis and obstruction of glottis. PREVIOUS CLASSIFICATIONS OF DYSPHONIAS: The best known classification of dysphonias was introduced by Perello. There are two groups: 1. organic dysphonias and 2. functional dysphonias. On the 8th Congress of the Union of European Phoniatrists, in Koszeg (Hungary, 1979), Majdevac proposed a new classification. CLASSIFICATION OF DYSPHONIAS: We are proposing a new classification according to the primary etiologic factor of dysphonias. In this paper, we shall consider four gropus: from the fifth to eighth. V DYSPHONIAS CAUSED BY PRIMARY ENDOCRINE DISORDERS: This group includes: 1. Dysphonia caused by pituitary disorders 2. Dysphonia caused by thyroid gland disorders 3. Dysphonia caused by parathyroid glands disorders 4. Dysphonia caused by pancreatic function disorders 5. Dysphonia caused by suprarenal function disorders 6. Dysphonias caused by sexual glands function disorders 7. Intersexuality. VI DYSPHONIAS CAUSED BY COMPLEX PROFESSIONAL REASONS: This group includes: 1. Permanent hyperkinetic dysphonia 2. Permanent hyperkinetic dysphonia with vocal cord nodules 3. Dysphonia caused by myogenic imperfect closure of vocal cords 4. Phonastenia. VII DYSPHONIAS CAUSED BY PRIMARY DISPLASTIC DISORDERS: This group includes: 1. Dysphonia caused by laryngeal hypoplasia 2. Dysphonia caused by laryngeal asymmetry 3. Dysphonia caused by epiglottal anomalies 4. Dysphonia caused by laryngeal diaphragm. VIII DYSPHONIAS CAUSED BY LARYNGEAL TUMORS: This group includes: 1. Dysphonia caused by benign tumors 2. Dysphonia caused by malignant tumors. CONCLUSION: Dysphonia is a disorder of phonation which originates from glottal level. Disorders of phonation require observation of an organism as a whole and studying all mechanisms which take part in voice production. This provides examination of voice disorders, their establishment and adequate treatment. PMID- 11759205 TI - [Importance of studying exposure of the population to radon and its daughters]. AB - INTRODUCTION: Radon and thoron are naturally-occurring radioactive gases, which are products of uranium and thorium decay series, respectively. Uranium and thorium occur widely in the environment, in rocks, soil, air, water, building materials, humans, etc. Radon daughters in the air are predominantly attached to aerosols. A minor part, normally less than 10%, occurs as unattached atoms or ions. The relative distribution of attached daughters in indoor air and equilibrium factor depend on many variables, such as the decay constant, the concentration and size distribution of aerosols and ventilation rates. Increased ventilation decreases the concentration of radon and daughters in the air. OCCURRENCE: Concentration of radon, thoron and their decay products in the air indoors, in mines or houses, is higher than outdoors. In houses, the level of radon daughters may be enhanced by radon from radium rich building materials, landfill, soil and bedrock under the house, radon rich water and by poor ventilation. CONCLUSION: In recent years, several evaluations of human health risks and estimations have been made in regard to the dose-response relationship and lung cancer risk attributable to inhaled radon daughters. Inhalation of radon and thoron daughters leads to deposition in the human respiratory tract and consequent irradiation. Deposition depends on various factors, such as the size distribution of aerosols to which the daughter products of radon are attached, and fraction of unattached daughters. On average, the dose to the basal cell layer in the lung is about 5 to 8 times higher than the dose in the pulmonary region. PMID- 11759206 TI - [Prevention of multiple organ dysfunction syndrome in severely injured patients- current approach]. AB - INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is frequent after trauma. Predisposing factors for MODS after trauma are: hypovolemic shock, massive volume replacement, time of resuscitation before hospitalization, systemic inflammatory response syndrome, infection, sepsis. Prevention of tissue hypoxia is a priority in prevention of MODS. MONITORING THE ADEQUACY OF TISSUE OXYGENATION: Assessment of tissue oxygenation and potential hypoxia is indirect, based on measuring aspects of whole body oxygen transport and uptake, some regional parameters and indirect biochemical markers. Assessing oxygen transport involves: clinical evaluation of the patient, delivery of oxygen to the alveoli, oxygenation of arterial blood, delivery of oxygen to the tissues (DO2), oxygen uptake (VO2), oxygenation of the mixed venous blood, lactate and assessment of regional PCO2 or pH. THERAPEUTIC PRINCIPLES: Haemodynamic optimization for improvement of perfusion and tissue oxygenation is of primary importance. Nutritional support antibiotic prophylaxis, pain relief, sedation and other therapeutic modalities allow patient to survive a trauma and decrease risk of systemic complications. CONCLUSION: Tissue hypoxia and oxygen debt in injured patients are major factors which determine development of MODS. Prevention of MODS starts with respiratory and circulatory resuscitation and monitoring of tissue oxygenation prehospitally and hospitally. The first line therapy, "goal directed therapy" is not obligatory. Nutritional support, antibiotic therapy, analgesia, sedation and other therapeutic modalities contribute the ability of injured patients to survive and decrease the incidence of MODS. PMID- 11759207 TI - [Suicides and attempted suicides with corrosive substances 1968-2000]. AB - The authors analyzed attempted and committed suicides with corrosive substances registered at the Department of the General Hospital of the Health Center "Dr. Gere Istvan" in Senta in the period 1968-2000. Out of 42 registered, there were 33 attempted and 9 committed suicides with corrosive substances. In regard to the total number of suicides attempted and committed with poisoning, these poisonings take the last place, that is they come after suicides by drug intoxication, organophosphorus compounds and rodenticides. Data analysis included substance, sex, education level, marital status, occupation and underlying disease. It has been established that in regard to attempted suicides there is no difference in sex distribution, but in committed suicides females prevailed. Most subjects were married, had elementary education and by profession most were housewives, workers and agricultural workers. The most common motives for suicide were family and marital conflicts as well as alcohol consumption. Depression and alcoholism were most frequent underlying diseases. According to gathered data, authors conclude that suicide attempts with corrosive substances are decreasing from year to year. Suicides are mostly attempted with concentrated alkalies, but committed with concentrated acids. Depression and alcoholism are the commonest underlying diseases in patients attempting suicide. Esophageal stenosis is the most common complication in attempted suicides, whereas gastric perforation with peritonitis and esophageal perforation with mediastinal abscess are the most frequent complications in committed suicides. PMID- 11759208 TI - [Diagnostic importance of the sonographic scoring system in differentiating between malignant and benign ovarian tumors]. AB - INTRODUCTION: There have been several different sonographic scoring systems developed for evaluation of particular characteristics of ovarian tumors in order to classify malignant diseases in the most objective way. The aim of this study was to evaluate diagnostic significance of our own scoring system and possibilities of its application in differentiation of malignant and benign ovarian tumors. MATERIAL AND METHODS: A prospective study comprised 177 women with different ovarian tumors. All patients underwent ultrasound examination using a unit with a 5 MHz probe. Certain tumor characteristics (size, morphology, septa, type of capsule and ascites) were estimated by scores from 0 to 2 whereas the sum of all scores presented the total score. A final diagnosis was made after histopathologic examination: group A--malignant ovarian tumors (n = 71) and group B--benign ovarian tumors (n = 106). RESULTS: The highest value of reliability in differentiation of malignant and benign ovarian tumors was score 6 and more than six (sensitivity 87.3%, specificity 91.5%, positive predictive value 87.3%, negative predictive value 91.5% and test accuracy 90.9%). DISCUSSION: A separate diagnostic problem during application of mentioned sonographic scoring system were solid malignant tumors with a low total score (4 and 5 scores) and benign tumors of complex consistence of high total score (7 and 8 scores). The total score 1-3 eliminates malignant tumors and the score from 9-10 eliminates benign type of tumors. CONCLUSION: High sensitivity (95.7%) is present at the total score of 5 and more than five, but low specificity (81.1%) and test accuracy (87%) gives advantage to the score 6 and more, where differences between separate statistical parameters are least present. PMID- 11759209 TI - [Allergic rhinitis as a possible etiologic cause eustachian tube dysfunction]. AB - INTRODUCTION: Allergic diseases of the upper respiratory tract are becoming one of the leading factors in the etiology of Eustachian tube dysfunctions. Eustachian tube dysfunctions are one of the three most significant etiologic factors of secretory otitis. MATERIAL AND METHODS: The most numerous group, aged 5-9 years, included 80% of subjects. Type B tympanogram was found in 173 (86.50%), and type C in 27 (13.50%) ears. Positive family anamnesis for allergic diseases was found in 26 (26%) subjects. A positive skin test for standard group in inhalatory allergen was present in 21 (21%) subjects. RESULTS AND DISCUSSION: Sex and age distribution of subjects correlate with data of other sources. A significantly higher incidence is found in the age group of 5-9 years. In presented sources the incidence of allergic diseases and Eustachian tube dysfunction is relatively wide and ranges between 20 and 50%. Results obtained by our research correlate with the mentioned values. CONCLUSION: This paper reports results of our own research of the incidence of allergic rhinitis, in cases of tympanometrically proven Eustachian tube dysfunction, in patients 5 to 19 years of age. Allergic rhinitis to inhalatory allergens was diagnosed in 21% of subjects. Based on the above mentioned we can conclude that one out of four patients aged between 5 and 19 with the diagnosed Eustachian tube dysfunction also suffers from allergic rhinitis. The consulted sources confirm that allergic rhinitis can be considered as one of the leading etiological factors of Eustachian tube dysfunction. PMID- 11759210 TI - [Potential risk factors for children in the family diet]. AB - INTRODUCTION: It has been proven that high-energy diet with predominance of saturated fatty acids, cholesterol, animal proteins and sugar increases disease incidence. The aim of this study was to determine the potential risk factors of family diet of schoolchildren in Subotica. MATERIAL AND METHODS: Evaluation of energy and nutrient intake in family diet (n = 357 families with schoolchildren) was examined by a Food Consumption Questionnaire during 7 days in February-March 1998. Data were elaboreted using a software "NUTQ". The potential nutritive risk factors were determined according to Recommended Dietary Allowances (RDA) index of dietary adequacy, as well as Population Nutrition Goals. RESULTS: Mean energy intake was 2197 kcal, where proteins made 14.64%, fats 41.39% and carbohydrates 43.97%. Mean intake of dietary saturated fatty acids (S) was 11.17%, of polyunsaturated fatty acids (P) 14.39%, of monounsaturated fatty acids 15.82%, dietary cholesterol 82.68 g/1000 kcal, dietary fiber 10.67 g daily, while the P/S ratio was 1.28. Analytical questionnaire of schoolchildren family diet shows that daily about 7.5% of children take in more than 30% of fats, 7% of them over 300 mg of dietary cholesterol, 65% of them over 10% of refined sugars, 50% of them over 10% of saturated fatty acids and all of them more than 6 g of NaCl and less than 20 g of dietary fiber a day. DISCUSSION: According to WHO recommendations, the average daily energy intake values are appropriate for boys, but exceeding for girls aged ten. Domination of meat, meat products, fats, oils, sugars, as well as mean intake of total fats, saturated fatty acids, potassium and sodium, represent potential nutritive risk factors for developing cardiovascular diseases, which are at the first place of morbidity and the second cause of mortality. In regard to our data from 1998, which have shown that among schoolchildren (n = 478) 10.04% boys and 11.47% girls were obese, 8.55% boys and 6.42% girls were overweight, 9.15% had hypercholesterolemia, 14.83% had hypertrigliceridemia and 17.28% had elevated level of LDL-cholesterol, we have to admit that preventive actions regarding healthy nutrition policy is necessary in our society. CONCLUSION: Nutritional risk factors in diet of average children in Subotica demand prompt preventive actions in order to prevent nutrition disorders. PMID- 11759211 TI - [Epidemiologic characteristics of onychomycosis--results of a retrospective study]. AB - INTRODUCTION: The term onychomycosis is used for fungal infections of the nail unit. Tinea unguium is defined as a dermatophyte nail infection. The aim of this study was to determine the epidemiological characteristics of onychomycoses. MATERIAL AND METHODS: Ambulatory patients of the policlinic department of the Clinic of Dermatovenereology in Novi Sad were included in this study. Every patient with clinically suspected nail changes was examined. Direct microscopy of nail clippings and isolation of fungi on Sabouraud agar were performed. The results were evaluated using standard statistic methods. RESULTS: During a one year-period (1995-1996) 70 cases of onychomycoses were registered that is 1.07% of the total number of patients examined in this period (N = 6535). The vast majority of observed patients were females (N = 47-67.14%), and male patients were significantly less frequent (N = 23-32.86%, p < 0.01). The most frequent type was dermatophyte onychomycosis (N = 39-55.71%), and the most often isolated agent was Trichophyton mentagrophytes (N = 38-54.29%). Manual workers were most often affected (N = 18-25.71%). Most patients were in the 41-50 year age group (N = 23-32.86%). The mean age of patients was X = 47.64 years (SD = 15.39). Table 4 shows the clinical duration of different types of onychomycoses. The longest clinical course was in the group of dermatophyte onychomycosis (20 years, one case). The mean clinical duration of the whole group was 26.81 months (SD = 40.04). Table 5 shows presence of other dermatomycoses associated with onychomycoses. Tinea pedis was the most frequently observed dermatomycosis (N = 9 60.00%). DISCUSSION: The incidence (1.07%) is something less than usual, and other findings are compatible with standard results. A lower incidence could be the result of the fact that children under 17 years are managed at the Institute of Mother and Child Health Care in Novi Sad. CONCLUSION: This study is a contribution to epidemiological investigations of onychomycoses. This disorder, with its social and medical importance and dubious treatment results, puts onychomycoses on high level of interest in modern dermatovenereology. PMID- 11759212 TI - [Congenital fistula of the stapedial footplate as an avenue for recurrent purulent meningitis]. AB - INTRODUCTION: Congenital fistula of the stapedial footplate is a rare cause of recurrent purulent meningitis and a diagnostic and therapeutic problem as well. CASE REPORT: We report a case of a stapedial fistula diagnosed intraoperatively in a 4-year-old boy, after recurrent meningitis. The boy was hospitalized at the Pediatric Clinic three times in a 6-month period because of recurrent meningitis. The applied anti-meningitis therapy presented with good general state of the child, but the main target was to discover the cause of recurrent meningitis. Immunologic and genetic investigations were performed. Otorhinolaryngologic findings nearly normal, except minimal asymmetry in the otoscopic finding. Eardrum was reddish with all other characteristics of a normal drum. The tympanometric curve was of type B/C on the right ear. MRI revealed hydrocephalus internus with signs of inflammation of mastoid cells and cavum tympani indicating explorative myringotomy and antrotomy. Intraoperatively, we found cerebrospinal fluid in the antrotympanic cavity, including malformation of the incus without contact with stapes and fistula on the middle part of the stapedial footplate with flow out of the perilymph. CONCLUSION: Perilymphatic fistula is a rare cause of recurrent meningitis, whereas congenital ear malformation may be a cause of recurrent meningitis, particularly in children. The diagnosis is intraoperative. The surgical treatment may be very difficult, often requiring revision of procedures especially if cerebrospinal fluid pressure is increased. PMID- 11759213 TI - [Lichen sclerosus et atrophicus--a diagnostic problem]. AB - INTRODUCTION: Lichen sclerosus et atrophicus (LSA) is a rare disease with etiology that has not been clearly defined up to now. This disease appears up to 10 times more frequently among women, than among men. It occurs at the age of 40 60. Anogenital site is the most common, but in 20% of cases it is extragenital. CASE REPORT: We report a case of a 78-year-old woman with skin lesions on the hand and face, that appeared 7-8 years ago after intensive sun exposure. When admitted to hospital, she had a butterfly-shaped livid erythema on cheeks and nose hypopigmentation on its edges. Atrophic plaques were formed in some areas of lesions. On the dorsal side of hand clear atrophic plaques were noticed. Pathohistological analysis of skin lesions revealed epidermal hyperkeratosis and atrophy with follicular hyperkeratosis, dermal edema, with subepidermal blistering and edematous hyalinized connective tissue. Direct immunofluorescence of the face lesion has shown presence of IgA, IgG and IgM deposits along the epidermo-dermal interface. Based on all findings the following diagnosis was made: Lichen sclerosus et atrophicus bullosus. DISCUSSION: Differentiation between chronic discoid lupus erythematosus and LSA presents a diagnostic challenge. Both diseases have some common pathohistological changes, but a single mixed inflammatory dermal infiltrate as well as edema and hyalinized connective tissue were the most important facts in making diagnosis. CONCLUSION: Lack of knowledge in regard to etiology of this disease has caused some problems in differential diagnosis. This disease hasn't always been a separate entity, but we expect that many things regarding the etiology and pathogenesis to be explained in the future. PMID- 11759214 TI - On sexual dimorphism of certain regions of the human brain. PMID- 11759215 TI - [Changes in peritoneal mesothelial cells in patients on peritoneal dialysis]. AB - INTRODUCTION: Some thirty years ago peritoneal dialysis (PD) became a respectable modality of renal replacement therapy. That is why peritoneal membrane attracted interest of investigators. Certain changes, known as uremic serositis, appear in morphology of serous membranes in end stage kidney disease (ESKD). The aim of our investigation was to examine the morphology of peritoneal lining cells in control group of healthy persons and morphology of peritoneal lining cells in patients on PD. MATERIAL AND METHODS: Peritoneal biopsies were taken in 10 healthy volunteers during the kidney donation and in 15 patients on PD during clinically indicated extirpation. Biopsy samples were prepared for standard routine HE staining and for plastic embedded fine sections studying. Sections were mounted in an ultramicrotome, stained with Toluidine blue (TB) and studied by light microscope (SM), while fine sections were mounted in an ultramicrotome and studied by transmission electron microscope (TEM). RESULTS: One layer mesothelium of the cuboidal or flattened lining cells were present over the lamina propria connective tissue. Mesothelial cells were overlapped like tiles on the roof. These cells were interconnected with different types of cell junctions (unpermeable, adhesion and communication junctions) positioned on lateral parts of the interdigitated cell membranes. A great number of microvilli were often present on the appical surface, as well as a kinocilia and lamellar bodies. Nuclei were euchromatic with well developed nucleoli. Many ribosomes, mitochondria, cisternae of rough endoplasmic reticulum (RER) and Golgi apparatus, lamellar bodies and lipid inclusions were present in the cytoplasm. Using TEM in analyzing fine sections of biopsies of patients on PD, characteristic ultrastructural changes including epithelial defects with only remaining parts of destroyed cells were established, as well as significantly greater number of rough endoplasmic reticulum (RER) cisternae and immature mesothelial cells in lamina propria indicating intensive regeneration of this epithelium. The cytoplasm of new mesothelial cells were of less electron density on TEM photomicrographs, whereas the nuclei of mesothelial cells in these patients were euchromatic with prominent nucleoli and numerous perichromatic granules and fibrogranular nuclear bodies, indicating cells of great activity. Cytoplasmic protrusions of different shape and content were often recognized on the apical surface of cells. Lamellar bodies were also present in this group of patients within the mesothelial cells, as well as between two mesothelial cells or on their apical surface. Mitochondria were picnotic in many of the mesothelial cells of peritoneum in this patient group. In these mesothelial cells intracytoplasmic paracrystaline inclusions were established. TEM photomicrographs showed basal lamina multiplication in this epithelium. CONCLUSION: Our findings comply with reports of other authors. It should be stressed that TEM examination detects characteristic ultrastructural changes in mesothelial lining cells of peritoneum in patients on PD, which could compromise the function of peritoneum as a membrane for dialysis. PMID- 11759216 TI - [Distribution of HLA class II antigens and allele linkage disequilibrium in the population of Vojvodina]. AB - INTRODUCTION: Polymorphism of human leucocyte antigens (HLA) is important in transplantation medicine, anthropological studies and paternity testing. MATERIAL AND METHODS: We investigated polymorphisms of HLA class II in population of Vojvodina by means of serologic typing using microlymphocitotoxicity test. We calculated the HLA-DR and HLA-DQ gene frequencies in 174 subjects. Haplotype frequencies, coefficient of linkage disequilibrium (delta values) and their statistical significant levels, were analyzed on the basis of these data. RESULTS: The most frequent HLA-DR and HLA-DQ alleles were: DR5(11) (gene frequency 0.138), DR4 (gene frequency 0.083), DR1 (gene frequency 0.077), DQ1 (gene frequency 0.388), DQ3 (gene frequency 0.197), and DQ2 (gene frequency 0.09). The highest positive values of coefficient of linkage disequilibrium (delta) were calculated for the following haplotypes: DR1DQ1 (delta value 0.07308708), DR2DQ1 (delta value 0.059846528), DR3DQ2 (delta value 0.06193263), DR2(15)DQ1 (delta value 0.039186022), DR5(11)DQ3(7) (delta value 0.04969439), DR7DQ2 (delta value 0.057985517). Significant differences between observed vs. expected haplotype frequencies were also considered for these haplotypes. CONCLUSION: This study indicates distinctiveness and specificity of the population of Vojvodina and highlights the importance of determining HLA frequencies in endogamic groups of Serbia. PMID- 11759217 TI - [Effect of sociodemographic characteristics on health status and quality of life in schoolchildren and adolescents in Yugoslavia]. AB - INTRODUCTION: Quality of life, as a term in medical literature, appeared 3 decades ago. During the 90s, first studies on quality of life among children and youth were presented. Child Health Questionnaire (CHQ) was recognized as the most constructive and clear to use. MATERIAL AND METHODS: The study was performed in a random sample of children and adolescents (No = 600) and their parents. The sample was stratified by age, sex, and socioeconomic status of parents. The measurement model was a Yugoslav adaptation of CHQ-CF87 and CHQ-PF50. DISCUSSION AND RESULTS: Quality of life is a complex phenomenon, impacted by the person's experience, beliefs, expectations and perceptions. Study results confirmed better scores on almost all scales for boys, younger subjects and children with better socioeconomic status. A study performed in USA using CHQ-CF87, showed almost invert results considering gender. Our experience indicates statistically significant differences on 5 scales in favor of boys. All scales showed statistical difference in regard to age, except physical functioning and role (social--physical), especially low scores for older ages. Regarding the socioeconomic status, statistical differences were found at the following scales: mental health scale, family activity scale and family cohesion, with low scores for the group. In general, children health was reported to be worse for less educated, not working, non-married, separated or divorced parents. CONCLUSION: Variations in health and quality of life components showed expected association with sociodemographic factors in both versions of questionnaires. Boys had better scores, as well as children of younger age and better social status. PMID- 11759218 TI - [Erythropoietin-beta in the treatment of anemia in patients with chronic renal insufficiency]. AB - INTRODUCTION: Anemia is an early sign of chronic renal failure (CRF). Although multifactorial in origin, insufficient erythropoietin (EPO) synthesis is one of the most important factors. Other causes are: decreased erythrocyte survival (from 120 days to 70-80 days), chronic blood loss (mainly gastrointestinal and gynecological), inhibitors of erythropoiesis, inflammatory cytokines (IL-1, TNF alpha, IFN-gamma) and malnutrition (folic acid, L-carnitine and vitamin B12 deficiency). Chronic blood loss may cause iron deficiency in about 25% of patients. Correlation between EPO level and glomerular filtration rate (GFR) is well preserved, but negative feed-back loop between hemoglobin and EPO is disturbed in patients with CRF. CONSEQUENCES OF GRF: The consequences of renal anemia are mainly cardiovascular; left ventricular hypertrophy (LVH) is often found at the start of dialytic therapy. Cardiovascular morbidity [especially LVH and congestive heart failure (CHF)] and mortality highly correlate with the degree of anemia. In addition, anemia affects patient rehabilitation and quality of life. It positively correlates with the degree of physical activity, sleep and general well-being. ERYTHROPOIETIN THERAPY: Optimization of erythropoietin therapy includes awareness of target hematocrit and hemoglobin, defining the renal anemia management period (RAMP), drug dosage and mode of application and significance of adjuvant therapy. Anemia should be treated early during the course of renal failure, even when GFR falls below 50 ml/min. According to dialysis outcomes quality initiative (DOQI) guidelines, target values are 0.33 0.36 L/L for hematocrit and 110-130 g/l for hemoglobin. Early administration is recommended especially in high-risk patients: the elderly, diabetics and those with coronary artery and peripheral artery diseases. EFFECTS OF EPO THERAPY: Individualization and close monitoring of therapy are very important and weekly rise in hematocrit (Ht) should not exceed 1%. More recent studies justify the normalization of Hb/Ht values--patients with normal Hb/Ht values have had the lowest mortality. In addition, normalization of Hb/Ht prevented LVH. Subcutaneous administration has priority compared to intravenous. Adjuvant therapy includes: iron, vitamin C and D, L-carnitine, folic acid, cytokines and growth factors. Intravenous iron administration has priority upon oral; target levels are 400-800 for ferritin um/ml and > 20 for transferrin saturation. Vitamin C (500 mg, after every hemodialysis) is very helpful in cases of functional iron deficiency. L carnitine stabilizes the membrane of erythrocytes and prolongs their lives. Folic acid (10 mg/day) enhances response to EPO. Apart from correction of hematological parameters, erythropoietin therapy significantly improves left ventricular hypertrophy, quality of life, nutrition, sexual activity, carbohydrate and lipid metabolism, cognitive function and sleeping function. Given in predialysis period, it may slow progression of renal failure, prevents cardiovascular and overall morbidity and improves survival in dialysis population. CONCLUSION: The reasons for inadequate erythropoietin response are unrecognized bleeding, iron deficiency and infection/inflammation. Adverse events are very rare and predictable; they can be avoided with careful dosage and follow-up of patients. In conclusion, EPO-therapy is well established and efficient for renal anemia in dialysis and pre-dialysis patients. PMID- 11759219 TI - [Obesity and respiratory tract disorders]. AB - INTRODUCTION: Although in the shade of metabolic and cardiovascular complications, respiratory tract disorders are very frequent and are predominant in extremely obese subjects with body mass index (BMI > 4O kg/m2), most often of gynoid type. CLASSIFICATION OF DISORDERS: These disorders can be classified into four groups: 1. Respiratory function disorders without alveolar hypovenitilation, 2. Pickwickian syndrome, 3. Sleep apnea syndrome and 4. Risks during surgical interventions. CONCLUSION: This study includes detailed discussion of mechanisms of origin, pathophysiologic characteristics and clinical signs of each of these disorders and at the end a review of their treatment. PMID- 11759220 TI - [Use of radionuclides in therapy]. AB - INTRODUCTION: In nuclear medicine therapy is based on deposition of certain doses of ionizing radiation in tumors or organ tissues. Regarding their linear energy transfer (LET) values and relative biological effectiveness (RBE), principal radiotherapeuticals are alpha-, beta-, beta/gamma- or electron-emitters. In principle, to achieve the desired therapeutic effect, a particular radionuclide should exhibit adequate physical, chemical and biological properties. However, considerable efforts are required in selecting an optimal radionuclide for a specific application and then, in the development of methods for its routine production. THERAPEUTIC USE OF RADIONUCLIDES: The paper reviews several aspects of use, properties and production of unsealed radiation sources which are intended to be administered for therapeutic purposes. It covers scientific and practical criteria involved in selecting the radionuclide from medical point of view. The main indications for use of radiotherapeuticals are in oncology and rheumathology. Besides well known, like 32P, 89Sr, 90Y and 131I, several other radionuclides are also listed. Some of them are already in routine use while the others are still under investigation. The main chemical forms of radionuclides and indications are revealed. Particular emphasis is put on the discussion on criteria which a radionuclide should fulfill regarding its physical properties (type, energy, half life, ratio and abundance of the particulate and gamma ray emission). Ideally, they should, together with chemical and biological properties, match with the in-vivo pharmacokinetics and localization of the radionuclide and/or radiopharmaceutical. The trend in modern nuclear medicine is introduction of radionuclides of very specific properties. This, on the other side, opens a question of their availability on the routine basis and at reasonable prices. This matter is also discussed in the present review. CONCLUSION: Production of radionuclides for therapeutic purposes (as well as those for diagnostics) is performed either in nuclear reactors or in cyclotrons. Advantages and disadvantages of each production are discussed. The main nuclear reactions for routine production of 32P, 89Sr, 90Y and 131I are given, as well as for production of several other reactor or cyclotron-produced radionuclides. These are, e.g., reactor-produced beta-emitter 169Er, beta/gamma emitters 67Cu, 153Sm, 165Dy, 186Re and electron-emitters 80mBr and 125I. Generators for production of alpha emitters 212Bi and 213Bi are also under development. It can be concluded that, at present, besides 131I, large activities of 32P, 89Sr and 90Y are available on regular basis. For many others, routine availability remains yet to be established. PMID- 11759221 TI - [The first non-Q myocardial infarct as a clinical manifestationn of acute coronary syndrome]. AB - INTRODUCTION: Non-Q myocardial infarction is only one of the possible clinical manifestations of acute coronary syndromes. Acute coronary syndrome is the most frequent cause of hospitalization in everyday cardiological practice. OBJECTIVES: 1. To evaluate the incidence of unstable angina and myocardial infarction in the group of patients admitted to hospital with diagnosis of acute coronary syndromes; 2. To evaluate the incidence of non-Q myocardial infarction in the group with index myocardial infarction; 3. To determine the frequency of different ECG changes in the subgroup with non-Q myocardial infarction. MATERIAL AND METHODS: The study was conducted at the Institute of Cardiovascular Diseases in Sremska Kamenica in the period between Jan. 1, 1997 and Dec. 31, 1999. Hospitalized patients with acute coronary syndromes (n = 3.337) were divided into subgroups with unstable angina (chest pain, ECG changes and normal level of CK) and with myocardial infarction (chest pain, ECG with/without changes, elevation of cardiac enzymes). Myocardial infarction without Q waves on ECG was considered to be non-Q myocardial infarction. Initial ECG changes (ST elevation, ST depression, inverted T waves, abscence of changes) were evaluated in patients with non-Q myocardial infarction who were not treated with Streptase. RESULTS: During a three-year period, 3.337 patients with acute coronary syndrome were hospitalized. 65.3% of them had unstable angina, while 34.7% suffered from myocardial infarction. In the group with myocardial infarction, 12.9% (280/2179) had reinfarction. 8.8% of patients were treated with thrombolytic agents, which prevented formation of Q waves in 24.6% of patients. In the group of patients who were not treated with thrombolytics, 196 patients (11.8%) fulfilled criteria for non-Q myocardial infarction. Incidence of initial ST elevation, ST depression and inverted T waves in those patients with non-Q myocardial infarction were 11.2%, 35.2% and 52.1% respectively, whereas 1.5% had no ECG changes. CONCLUSION: Both incidence of unstable angina and non-Q myocardial infarction, as manifestations of acute coronary syndromes, and incidence of newly formed ST elevation, which is one of the forms of initial ECG changes in non-Q myocardial infarction, are significantly lower than those found in literature. PMID- 11759222 TI - [Suicide and attempted suicide with rodenticides from 1968 to 2000]. AB - INTRODUCTION: The paper reviews rodenticides in use in Yugoslavia, their mechanism of action, typical clinical picture as well as general and specific treatment of poisoning. OBJECTIVES: Our aim was to present interventions performed in urgent treatment considering the fact that the mortality rate in rodenticide poisoning, especially with zinc phosphide is really small. MATERIAL AND METHODS: The study included history data of patients who attempted and committed suicide with rodenticides. Data analysis was done in regard to the poison, sex, qualification, marital status, motives, underlying disease and interventions performed. RESULTS OF INVESTIGATION: The total number of attempts was 88, out of which 85 were attempted and 3 committed suicides, mostly with zinc phosphide: 34 attempted (40%) and 3 committed (100%). There were 66 (75%) patients with elementary school, 61 (69%) patients were married, 36% were workers and 35% housewives, while marital or family conflicts were motives for suicide in 52 (59%) patients. There were 30 (34%) patients with depression, 28 (32%) were alcoholics and 23 (26%) patients suffered from neurosis. In 17 patients (19%) ambulatory gastric lavage was done, while in 56 (64%) patients it was done in the hospital. DISCUSSION: Attempted and committed suicides were most commonly done with zinc phosphide, and then come rat poisons. A considerably small number of interventions were recorded in the surrounding outpatient clinics, but it is only natural, because the furthest outpatient clinic is about 40 km away, so patients can make it to the hospital within 20 minutes and get adequate medical care. Although gastric lavage was excessive with activated charcoal and laxans, most lavages were inadequate and performed with water, not solution of sodium bicarbonate. CONCLUSIONS: Suicides with rodenticides are still actual in medicine. Women attempt and commit suicide with rodenticides more often. Zinc phosphide is the most frequently used poison. These patients must be admitted to hospital and observed for at least three days. Zinc phosphide poisoning requires excessive gastric lavage with sodium bicarbonate solution, application of charcoal, laxanes, calcium preparations with excessive osmotic diuresis, whereas in poisoning with coumarin preparations, apart from gastric lavage, application of charcoal and laxanes as well as excessive osmotic diuresis, vitamin K and Dicynone are necessary. PMID- 11759223 TI - [Specificity of lipid and lipoprotein status in healthy students at the University of Novi Sad]. AB - INTRODUCTION: The aim of this study was to determine the frequency of hyperlipoproteinemias and normolipidemic dyslipoproteinemias, and distribution of desirable, borderline and high-risk values of certain lipid status parameters in healthy young individuals. MATERIAL AND METHODS: In this investigation we examined 213 students of the University of Novi Sad of both genders, 20-30 years of age. Standard biochemical methods were used to determine values of total serum cholesterol, triglycerides, HDL cholesterol, and lipoproteins by cellulose acetate electrophoresis. The level of LDL cholesterol and LDL/HDL cholesterol and total/HDL cholesterol ratios were calculated. RESULTS: In this group hyperlipoproteinemia was established in 42.3% of cases and normolipidemic dyslipoproteinemia in 65.3%. Total serum cholesterol was minimally elevated in 39.0% of tested students, elevated with high risk in 3.3% and triglycerides were minimally elevated in 1.0%. Presence of elevated LDL cholesterol (24.4% minimally and 13.2% with high risk) is remarkably significant. HDL cholesterol is minimally decreased in 54.0% of tested students, and severely in 3.3%. DISCUSSION: The tested parameters deviate from desirable levels with an alarmingly high frequency, given the fact that this is a group of healthy young individuals with no previous history of lipid and lipoprotein metabolism disorders. It can be hypothesized that a joint hyper Lp(a)-lipoproteinemia can exist with a significant occurrence. These results could be associated with similar disorders in families of tested students, unhealthy food habits and lifestyle, use of oral contraceptives and smoking. CONCLUSION: Our results point to the need for performing gradual laboratory diagnostic procedures for routine check-ups in students. PMID- 11759224 TI - [Noise as a stress factor for the onset of hearing disorders in workers using drilling equipment]. AB - INTRODUCTION: Noise is one of the commonest environmental pollutants and it is defined as a sound which bothers, irritates, which is unpleasant and can damage hearing. The degree of negative effects of noise depends on its intensity, spectrum of frequency, nature, duration of exposition and individual sensibility. PURPOSE: This work is supposed to establish the degree of correlation between hearing damage and professional exposition to one of physical stressors of work environment--noise. MATERIAL AND METHODS: Investigation regarding work conditions included intensity and frequency analysis of noise at workplaces. The examination sample included 101 workers of "NIS--Naftagas" section "Hidrosonda" employed as drilling workers. The control group consisted of 50 workers not exposed to noise or any other professional influences, like workers from the examination sample. RESULTS: The results on the observed workplaces show that noise is of high intensity and bad frequency spectrum. Exposition of workers to noise is a highly important factor for hearing damages (p = 0.002). The relative risk for hearing damage is four times greater in relation to the control group (odds ratio 4.1). Attributable fraction (preventive potential) of noise factor is 61%. Smoking associated with exposition to noise multiplies the risk of hearing damage (odds ratio 5.8) while with non-smokers the risk decreases (odds ratio 3.0). DISCUSSION: Professional hearing disorders occur slowly and increase with time spent at noisy workplaces. At the beginning it presents with buzzing in ears and dizziness followed by latent phase after which hearing disorders occur. Tone audiometry is used to register first signs of hearing loss, whereas manifestations in social contacts come later. CONCLUSION: Once diagnosed hearing disorders cannot be cured so a lot more care should be paid to this problem. It is necessary to provide adequate work conditions by applying appropriate technologies, tools, work organisation, personal protection equipment, as well as previous and periodical examinations of hearing by tone audiometry before employing workers and during their work in noisy conditions. PMID- 11759225 TI - Direct intracoronary stent implantation. AB - The standard stent implantation technique requires routine predilatation of the target lesion with balloon catheter. Since occurrence of complications is possible, direct stent implantation without previous dilatation has been performed recently. In this study, a complex case of coronary lesion treated with direct stent implantation in a patient with unstable angina after diaphragmal myocardial infarction was reported. A coronary angiography finding indicated presence of severe eccentric stenosis in the proximal third of the dominant right coronary artery. The system of the left coronary artery was without stenotic lesions. After antiaggregation combination of aspirin and ticlopidine, the stent was successfully implanted and dilated under the pressure of 14 atmospheres. The control coronary angiography did not show residual stenosis of the right coronary artery. The patient was discharged without subjective discomforts for further out patient treatment. PMID- 11759226 TI - [Small-plaque parapsoriasis: case report]. AB - INTRODUCTION: Small plaque parapsoriasis is a relatively rare, chronic, idiopathic dermatosis, most often seen in middle age people. This disease shows a definite male predominance of approximately 3-4: 1. It is characterized by presence of round or oval erythematous, slightly scaly plaques on the limbs and trunk, which histologically reveal mild eczematous changes. CASE REPORT: A male patient, 61 years of age, was admitted to the Clinic of Dermatovenereology in Novi Sad due to long persisting erythematous patches on his upper and lower limbs. Plaques were of oval and round shape, pretty well marginated. They were of light red colour, covered with fine scales with a slightly wrinkled surface. He complained of itching. Laboratory findings showed no abnormalities. Histopathologic examination of the skin specimen revealed epidermal atrophy, focal parakeratosis, perivascular dermal infiltrate of mononuclear cells with exocytosis in the epidermis. This finding was compatible with the clinical diagnosis. After treatment with topical corticosteroid cream combined with whole body exposure to sunlight irradiation, vast majority of skin lesions regressed. DISCUSSION: The clinical course of small plaque parapsoriasis is very long. The plaques are remarkably stubborn, responding to treatment with steroid creams or to natural or artificial sunlight, but usually reappearing promptly when treatment is discontinued. The patches increase in number for a time, and then remain relatively constant for a long time. A small minority of cases clears entirely. Recent studies provided evidence of monoclonality and immunophenotypic abnormalities. Rearrangement of T-cell receptor genes was demonstrated by using PCR method. Detection of monoclonal T-cell populations in skin lesions, as a characteristic of lymphoproliferative diseases, forced some authors to include this dermatosis into a group of abortive cutaneous T-cell lymphomas. CONCLUSION: This case deserves a long and probably life-long clinical and histological assessment, especially due to new knowledge about the possible nature of this disease. PMID- 11759227 TI - [Postoperative pain as the fifth vital parameter]. AB - INTRODUCTION: Acute postoperative pain and its therapy is a great challenge for all health-care providers in operative medicine today. Despite development of new analgesic drugs and different therapeutic modalities in pain treatment, acute postoperative pain represents a negative experience for many surgical patients. MATERIAL AND METHODS: By reviewing relevant medical articles on this topic, we tried to find answers on the reasons why many surgical patients have pain in the postoperative period despite implementation of modern and powerful analgesic therapy like patient-controlled analgesia (PCA), spinal/epidural opioids and regional analgesia. RESULTS: The reasons of inefficacy of many analgesic therapeutic methods are multiple. One of them is the attitude of patients and healthcare workers to pain. Many of them consider pain is a natural and physiological consequence of different diseases and pathological conditions and moderate to severe pain is considered as acceptable consequence of surgery. Another important factor contributing to undertreatment is that pain is invisible in most hospital wards: severity of pain is not assessed, and patients are reluctant to "complain." Unless severity of pain is assessed on a routine basis, pain cannot be effectively treated. Thus, one of the most important changes in the process of improving the efficacy of pain treatment is to introduce pain assessment as the fifth vital sign in addition to the traditional four vital signs (temperature, pulse, blood pressure and respiratory rate). DISCUSSION: Introduction of the "fifth vital parameter" would solve many problems in postoperative pain therapy, because healthcare workers take vital signs very seriously both for monitoring and treatment. By frequent measuement and registration of pain intensity and by organization of teams for treatment of postoperative pain, analgesic therapy would be more efficient, and whole therapy of surgical patients would be more qualitative. Undertreatment of pain can have very serious consequences; delayed improvement, change of immune system, changed answer to stress, appearance of vegetative symptoms and possibility of permanent changes in peripheral and central nervous system resulting in chronic pain syndrome. These effects are very harmful, changing quality of life of the whole family because the treatment of chronic pain syndrome is very difficult and expensive. CONCLUSION: Anesthesiologists have a central role in perioperative treatment of surgical patients (from the preoperative preparation through anesthesia and intraoperative monitoring to postoperative treatment and monitoring at the department of the intensive care and at the department of postanesthetic care). Due to abovementioned and familiarity with many therapeutic modalities, like spinal/epidural application of analgesics, regional anesthesia/analgesia many clinicians and pain specialists consider anesthesiologists are those who can organize and supervise teams for acute postoperative pain services. PMID- 11759228 TI - [The beginnings and development of diagnostic imaging in nuclear medicine]. AB - INTRODUCTION: The phenomenon of radioactivity was discovered in 1896 by Antoin Henri Becquerel, but its application in visual diagnostics started about fifty years later. RECTILINEAR SCANNER: It was constructed by B. Cassen and ass. in 1949, when first scintiscans were obtained. Technical improvements have been made 1950-1956 (B. Cassen and ass., R. Newall and ass., P. Bell, D. Kuhl). Soon after appearance of the first Cassen's scanner, commercial production began. GAMMA CAMERA: It was invented and constructed by H. Anger in 1957, improvements being made from 1958 to 1963. Gamma cameras are being commercially produced and sold since 1962; about ten years later they become widely used, and soon they pushed out the scanner from visual diagnostics. COMPUTER: Its use in scintigraphic diagnostics started in 1964 (H. Shepers, D. Wincler, D. Brown). From 1965 to 1974 various centers developed their own computer programs; after 1974 computers with incorporated nuclear medicine software packages became commercially available. TOMOSCINTIGRAPHY (SPET) AND POSITRON TOMOGRAPHY (PET): Numerous attempts to obtain tomographic images of organs using scanners and gamma cameras were made between 1963 and 1973 (D. Kuhl and R. Edwards, H. Anger, N. Charkes and R. Somburanasin et al.). The concept of contemporary single photon emission tomography (SPET) device was developed between 1974 and 1977 (J. Keyes and ass. and R. Jaszczak and ass.), while commercial production started in 1982. First cyclotrons for production of positron emitters, a prerequisite for positron emission tomography (PET) diagnostics, emerged in hospitals in 1955, and in last ten years they are being commercially made for these purposes. H. Anger (1959), M. Phelps, E. Hoffman and M. Ter-Pogossian (1975) set the grounds of PET; commercial production of PET systems started thereafter. CONCLUSION: Visual diagnostics in nuclear medicine reached its zenith in clinical practice during 1970-1980. It is partly pushed into the background by new imaging techniques (US, CT, MRI), but it only initiated further improvements (SPET, PET). PMID- 11759229 TI - [Rheumatoid arthritis: determination of the current status]. PMID- 11759230 TI - [Rheumatoid arthritis: new developments in the pathogenesis with special reference to synovial fibroblasts]. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is mainly characterized by synovial hyperplasia, pathological immune phenomena and progressive destruction of the affected joints. Various cell types are involved in the pathogenesis of RA including T cells, antigen presenting cells, and endothelial cells. Recent experimental evidence suggests that the CD40/CD154 system might play an important role in the development of RA. Our experimental approach focuses on RA synovial fibroblasts (RA-SF) that are able to destroy articular cartilage independent of inflammation. To elucidate the specific role of those cells in RA pathophysiology the following questions are currently addressed: 1. Which mechanisms do activate the RA-SF? 2. How do the activated RA SF attach to the cartilage? 3. How do RA-SF destroy cartilage and bone? Which mechanisms do activate the RA-SF? The process of activation is poorly understood. It is unclear, how far the synovial hyperplasia of RA resembles tumor diseases. Along this line some contradictory results exist concerning the role of the tumor suppressor protein p53. Some investigations could show the expression of p53 in the synovial lining including p53 mutations in RA synovium and in RASF, while other research groups could not confirm these data. Our group has demonstrated that the tumor suppressor PTEN was less expressed in the synovial lining of RA than in normal synovium, but no PTEN mutations could be found in the RA-SF. In addition, the in vivo and in vitro expression of the anti-apoptotic molecule sentrin suggests a functional resistance of RA-SF to undergo apoptosis. Although it is still unclear, whether certain viruses or viral elements are involved in the pathogenesis of RA (cause, consequence or coincidence?), certain viruses could play a role in the pathogenesis of RA. The endogenous retroviral element L1 was found to be expressed in the synovial lining, at sites of invasion as well as in RA-SF grown in vitro. Moreover, the data indicate that after the initial activation of L1 downstream molecules such as the SAP kinase 4, the met protoonocogene and the galectin-3 binding protein are upregulated. How do the activated RA-SF attach to the cartilage? It has been suggested that integrins mediate the attachment of RA-SF to fibronectin rich sites of cartilage. Intriguingly, other adhesion molecules such as the vascular cellular adhesion molecule-1 (VCAM) and CS-1, a splice variant of fibronectin, are synthesized by RA-SF. By binding to these adhesion molecules, lymphocytes that express the integrin VLA-4 could be stimulated and thereby maintain the inflammatory process. Osteopontin is an extracellular matrix protein, which is associated with matrix adhesion and metastasis in tumors. In RA synovium, osteopontin was detectable in the synovial lining and at sites of invasion. How do RA-SF destroy cartilage and bone? The destruction of cartilage and bone in RA is mediated by matrix metalloproteinases (MMPs) and cathepsins. MMPs exist as secreted and as membrane bound forms. In vitro models are being developed to simulate the invasive process of RA-SF. In an in vitro model developed in our laboratory, the treatment of RA SF with anti-CD44 or anti-interleukin-1 (IL-1) minimized matrix degradation of RA SF. On the other hand, co-culture of RA-SF and U937 cells as well as application of interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) increased the invasiveness of RA-SF. Gene transfer of bovine pancreas trypsin inhibitor (BPMI) or interleukin-10 (IL-10) reduced the invasion of RA-SF, while transduction of interleukin-1 receptor antagonist (IL-1Ra) was chondroprotective. Double gene transfer of IL-10 and IL-1Ra resulted in both inhibition of invasion and chondroprotection. PMID- 11759231 TI - [Clinical experience with TNF-blockers]. AB - Recently, biologic agents have become available for the treatment of rheumatoid arthritis. Such agents, the so-called TNF blockers, selectively inhibit TNF alpha, a dominant proinflammatory cytokine. They allow good suppression of the disease activity in many patients. Even in nonresponders to conventional disease modifying antirheumatic drugs (DMARDs) a good response may be achieved. The anti erosive effect appears to be excellent. Major advantages are the fast response and good overall safety. Constitutional symptoms often disappear rapidly, which may contribute substantially to the gain in quality of life. Efficacy and safety are maintained even in long-term use. Because of certain risks and high costs TNF blocking agents should be reserved for patients who respond poorly to conventional DMARDs or do not tolerate them. PMID- 11759232 TI - [New therapy developments in rheumatoid arthritis]. AB - Despite the anti-TNF alpha based progress in the treatment of RA, it is necessary to further optimize study designs and reports (Etanercept/MTX combination with results of radiological progression; publication of D2E7 trials; combination of D2E7 with MTX). Moreover, innovative immunobiologicals (PEG-TNFRI, PEG-TNF alpha antibody fragments, soluble TNFRI, CTLA4-Ig, CD40 ligand antibody, antibodies against IFN-gamma, IL-6, IL-12, IL-15, IL-18, complements), inhibitors of TNF alpha translation (peptides, anti-sense constructs) or TNF alpha synthesis (targeting NF kappa B, p38 MAP-kinase, phosphodiesterase IV, TNF alpha converting enzyme) are forthcoming. Principally different are inhibitors of complement convertases or collagenase as well as vaccination studies or trials trying to induce T cell anergy. Furthermore, for patients with MTX side effects, alternative DMARDs need to be tested along with TNF alpha blockers. Combination studies of TNF alpha constructs with other immunobiologicals (anti-CD4, IL-4, IL 10, IL-1RA) should be evaluated. To date, TNF alpha blockers have been evaluated in very early RA. Finally, a step-down trial will test whether--after induction of remission with a TNF alpha blocker plus MTX--replacement of the TNF alpha blocker with MTX alone or in combination with leflunomide will be able to keep disease activity suppressed for a longer duration. PMID- 11759233 TI - [Clinical quality management in rheumatoid arthritis]. AB - Clinical quality management in rheumatoid arthritis (RA) aims at reducing inflammatory activity and pain in the short term and damage and disability in the long term. In the "Swiss Clinical Quality Management in rheumatoid arthritis" (SCQM) project, which started in 1997, a measurement-improvement system with feedback reports allows the rheumatologists to follow their RA patients with the aim of improving the quality of outcome. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). The feedback is used by the individual rheumatologist to optimize the therapy of his/her RA patients. Beside the aim of improving the quality of treatment, the SCQM projects wants to build a Swiss cohort of RA patients, to improve the collaboration of rheumatologists in the clinic and in practice and to establish standards of treatment in RA. In this paper we describe the SCQM project in detail, we show two cases illustrating the usefulness of the SCQM in the management of individual RA patients, and we present the cross sectional analysis of the first 1223 RA patients included in the project. PMID- 11759234 TI - [Outcome measurement in musculoskeletal diseases: recommendation for a core set of scales for use in rehabilitation]. AB - By application of a standardized core set of outcome measurement instruments, comparison between studies as well as meta-analyses in rehabilitation research can be facilitated. The German Society for Rheumatology has commissioned its working group on rehabilitation with the development of a proposal for such a core set of outcome measurement instruments. In a first step, dimensions for outcome measurement in rehabilitation were defined by a group of experts which represented rehabilitation hospitals, acute care hospitals, and research groups specialized in outcome measurement. The Delphi method was used in a multiple step consensus process. In a second step, instruments and procedures to operationalize the relevant dimensions were chosen. Reliability, validity, sensitivity to change, and practicability were used as criteria for selecting measurement instruments. The main intention of the proposed core set of outcome measurement instruments is to facilitate the processes of planning and carrying out rehabilitation research studies. Furthermore, the proposed instruments can be used for clinical documentation systems as well as for internal or external quality assurance programs. PMID- 11759236 TI - [Chrysiasis]. AB - We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment. PMID- 11759235 TI - [Bone density and 25-OH vitamin D serum level in patients with systemic lupus erythematosus]. AB - OBJECTIVE: To clarify the influence of vitamin D metabolism on bone mineral density (BMD) or bone metabolism in patients with systemic lupus erythematosus (SLE). METHODS: 57 consecutive patients in our department (mean age 33.9 years, 44 female, 13 male) were studied. BMD was measured with dual-X-ray absorptiometry at the lumbar spine and femoral neck. Biochemical investigation of bone metabolism included measurement of vitamin D metabolites, intact parathyroid hormone (PTH), serum osteocalcin und urinary pyridinoline-crosslink excretion. RESULTS: 25 patients had 25-OH cholecalciferol serum values below the normal range after adjustment for seasonal changes; 9 patients were severely vitamin D depleted with 25-OH vitamin D serum values below 5 ng/ml. Low 25-OH-vitamin D was significantly associated with high disease activity. Mean 1.25 (OH)2-vitamin D, PTH, osteocalcin and crosslink excretion were in the normal range. Thirty-six patients had normal BMD; 5 patients had osteoporosis according to WHO diagnosis criteria. No correlation of biochemical parameters of bone metabolism with BMD was found. CONCLUSION: Severe vitamin D depletion was common in this group of patients with SLE even after adjustment for seasonal variations, especially in patients with high disease activity. Therefore, D-hypovitaminosis should be included in the differential diagnosis in patients with SLE presenting with low bone mass. PMID- 11759237 TI - [Presentation of the Dusseldorf Competence Center]. PMID- 11759238 TI - [In the best English manner. On the 200th anniversary of the death of William Herberden (1710-1801)]. PMID- 11759239 TI - [Considerations in bilateral cochlear implant management]. PMID- 11759240 TI - [Electronic data processing-assisted organization of interdisciplinary universal hearing screening in Saarland]. AB - BACKGROUND: Despite many recommendations and obvious advantages universal auditory screening in new-born children is only beginning to be implemented in the German health system. METHOD: We report on a multistage screening project based on otoacoustic emission measurements. One of the major disadvantages of such programs is the comparatively low specificity of otoacoustic emission measurements which leads to the need for a large number of re-measurements. Thus, the organisation of follow up screening failures is one of the most important factors that influence the effectiveness of screening programs. An additional problem is a drop-out rate which can be as high as 30% of the children that have to be retested. RESULTS: In our program we tried to solve these problems by combining primary screening in maternity wards with retesting by paediatricians using the routine examinations of children (U3 and U4) that are done for almost 100% of German babies. In addition, the data from the children that were screened and that have to be screened are transferred to a central data management system. CONCLUSION: Using this system, the follow up of any individual child can be monitored until a hearing loss has been diagnosed or excluded. Therefore early therapy of children with impaired hearing is possible and psychological and social defects can be avoid. PMID- 11759241 TI - [Endotracheal silicon stents in therapy management of benign tracheal stenoses]. AB - BACKGROUND: Advances in endoscopic technique and the development of new materials have made stenting an interesting alternative to surgical treatment for extended tracheal stenoses. This 5 years' retrospective study describes long term results of silicon stents in patients with benign chronic tracheal stenoses. PATIENTS AND METHODS: 45 adult patients (mean age: 45 years) had endotracheal Dumon (Endoxane) stent placement as surgical therapy was not indicated. Fiberoptic controls were performed every 3-6 months. RESULTS: In 42 patients therapy proved successful with improved ventilation and high level of tolerance. Acut stent-removal was necessary in 2 patients because of edema of the vocal cords, in 1 patient because of stent independent paralysis of both recurrents nerves. Further complications included migration (16.6%), granuloma formation (33.3%) and airway obstruction due to heavy secretion (2.3%). CONCLUSIONS: Long term results have shown that this technique is associated with high efficiency and infrequent complications which are not life-threatening. Advantages consist in a minor-invasive technique with small expenditure of time. PMID- 11759242 TI - [Mechanisms of invasiveness of cancers of the head and neck region]. AB - BACKGROUND: Squamous cell carcinomas of the head and neck region are highly aggressive cancers. Survival of these patients critically depends on the prevention of locoregional recurrences. A locoregional relapse is associated with an invasive growth pattern of the primary cancer. Thus, we need to understand regulatory mechanisms of cancer invasion to be able to develop therapeutic strategies, which may help to improve survival in this patient population. METHOD: Literature search. RESULTS: Certain tumor proteases are required for invasive growth of head and neck cancers. DISCUSSION: It is our understanding that further indepth investigation of mechanisms involved in the regulation of protease expression may help to develop treatment strategies, which improve survival by reducing the invasive capacity of head and neck cancer cells. PMID- 11759243 TI - [Serum concentrations of soluble adhesion molecules sICAM-1 and sVCAM-1 in patients with malignant ENT tumors]. AB - BACKGROUND: Adhesion molecules are implicated in various stages of tumor progression and metastasis. Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were recently described. The aim of this study was to determine a differences in concentration of these molecules in patients with head and neck squamous cell carcinoma (HNSCC) compared to healthy controls. PATIENTS AND METHODS: We investigated the circulating levels of sICAM-1 and sVCAM-1 in sera from patients with various head and neck squamous cell carcinomas (n = 52) as well as from normal, healthy controls (n = 35). Serum concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Student's t-test was performed. RESULTS: The majority of the patients with HNSCC were found to have high concentrations of sICAM-1 and sVCAM 1. The mean level of sICAM-1 in patients was 313 ng/ml and in the control group 237 ng/ml (p = 0.0005). The mean level of sVCAM-1 in patients was 624 ng/ml and in the control group 435 ng/ml (p = 0.009). The concentrations of sICAM-1 and sVCAM-1 were significantly higher in HNSCC patients. CONCLUSIONS: These results show the difference in expression of these adhesion molecules in patients with HNSCC compared to healthy controls. Endothelial adhesion molecule determination may find clinical applications in the follow-up of cancer therapy. For this reason, studies incorporating the longitudinal follow-up of patients are required. PMID- 11759244 TI - [Surgical treatment of differentiated thyroid gland carcinoma. Technique and morbidity in paratracheal lymph node excision]. AB - BACKGROUND: The extent of cervical lymphadenectomy in treatment of differentiated thyroid cancer is controversial. Technique and results of paratracheal lymphadenectomy are presented to demonstrate safety of cervical lymphadenectomy procedures. PATIENTS AND METHODS: 68 Patients with differentiated thyroid cancer underwent total thyroidectomy and extended lymphadenectomy in a standardized technique. The pre- and paratracheal and the lateral lymph node compartments were cleared. RESULTS: Permanent pareses of recurrent laryngeal nerve or permanent hypocalcaemias were not observed. 3 patients developed transient recurrent nerve palsy, 26 patients transient hypocalcaemia (Ca2+ > 1.7 and < 2.2 mmol/l). In 3 patients mild voice disturbances, probably due to superior laryngeal nerve dysfunction were observed. In 1 patient short-time tracheotomy was performed. 1 patients showed permanent Horner's syndrome. CONCLUSIONS: Thyroidectomy with extended lymphadenectomy achieves removal of all cervical tumor masses without relevant morbidity. The distribution of metastatic lymph nodes underlines the necessity of extended lymphadenectomy. PMID- 11759245 TI - [Eicosanoid metabolism in peripheral blood cells in patients with cystic fibrosis]. AB - BACKGROUND: The autosomal recessive inherited cystic fibrosis is the most common genetic disorder in white patients. Disturbances in the eicosanoid metabolism seem to play an important role in the pathogenesis of the disease. The present study shows examinations on the release of prostaglandin E2 (PGE2) and peptide leukotrienes (pLT) in peripheral blood cells. PATIENTS AND METHODS: In this respect heparinised blood samples of 10 cc were obtained from 25 patients with cystic fibrosis. The peripheral blood cells were separated from the remaining blood components. PGE2 and pLT were measured by a particularly developed sensitive enzyme immunoassay with specific monoclonal antibodies. Both the basal release of the metabolites and the concentrations after stimulation with arachidonic acid (AA) were explored. The control group consisted of 25 healthy individuals. RESULTS: A distinct elevation in the basal release of pLT compared to the control group was noticed. Further stimulation with AA could only be achieved to a remarkably smaller extent. In contrast to these findings no elevation of the basal release of PGE2 and no stimulative effect of AA could be detected. In general we observed a distinct shift in the eicosanoid metabolism in favour of pLT and their proinflammatory effects. CONCLUSIONS: The increased synthesis of pLT in patients with cystic fibrosis seems to play an important role in the pathogenesis of the disease. Future studies will have to proof, if we can achieve any improvement in the clinical courses in patients with cystic fibrosis using leukotriene receptor antagonists or 5-lipoxygenase inhibitors. PMID- 11759246 TI - [Transient facial nerve paralysis during flight]. AB - Transient facial paresis in divers and, in particular, in fliers is a very rare condition that apparently occurs only once in the lifetime of most patients. The cause involves is the co-occurrence of several factors, and dehiscence in the facial nerve canal cannot be considered the only cause. Affected patients must be calmed and an explanation provided. PMID- 11759247 TI - [Nitinol stent implantation in benign esophagotracheal fistula]. AB - The self-expanding nitinol stent is easy to handle and well tolerated. It offers an improved method in the treatment of perforations of the upper aerodigestive tract. It is easily implantable with rigid and flexible endoscopes. A 45-year-old female patient developed a tracheal necrosis after polytrauma and protracted intubation and ventilation. The permanent cuff pressure caused a 5-cm long fistula located at the posterior trachea 3 cm above the carina. After stabilization of the general condition and spontaneous reduction of the fistula length to 2 cm, we implanted the silicon-covered esophageal stent. Daily bronchoscopic examination was done before and after implantation of the stent. Two days after implantation, we were able to remove the blocked tracheostomy tube. Immediately oral nutrition was possible without complications. Because of its easy and fast application without any complications, the new type of nitinol stent is a promising alternative for ear, nose, and throat patients in bad general condition to provide fast and safe treatment in benign tracheoesophageal fistulas. PMID- 11759248 TI - [Salivary foaming as a complication of local anesthesia with lidocaine]. PMID- 11759249 TI - [Slowly progressing peripheral facial paralysis]. PMID- 11759250 TI - [Possible errors in pure tone and speech audiometry]. PMID- 11759251 TI - [Education for the prevention of asthma morbidity and mortality]. PMID- 11759252 TI - [Radiological findings in patients with perennial allergic rhinitis]. AB - BACKGROUND: Rhinitis is clinically defined by obstruction, sneezing, pruritus and rhinorrhea. MATERIAL AND METHOD: There were studied 69 consecutive patients, from clinical immunology and allergy service of Hospital de Especialidades del Centro Medico Nacional Siglo XXI. RESULTS: 53 of them were women and 16 were men, all of them with ages between 15 and 55 years. They all had perennial allergic rhinitis, 50.7% of them had atopy, 47.8%, asthma as an added disease, 27.5%, nasal polyposis and 44.9%, sinusitis, in maxillary sinus 59.9%, in ethmoid 36.2% in 7.2% frontal. With septal deviation 33.3%, in 7.2% septal deviation with spur, obstruction of the osteomeatal complex in 4.3%, turbinate hypertrophy in 53.5%, polyps in 27.5% and bullous conchae in 7.2%. The diagnosis was performed by axial computerized tomography of paranasal sinuses. The chi square determined the association between structural alterations and the presence of sinusitis, with p = 0.001, with close relation between allergic rhinitis and sinusitis. CONCLUSIONS: Diagnosis and appropriate treatment proved to be very important in handling this disease. PMID- 11759253 TI - [Desensitization to human recombinant DNA insulin in an adolescent with insulin dependent diabetes mellitus]. AB - BACKGROUND: Adverse reactions to drugs have increased in the last years, about 15% of all side effects are thought to be immune mediated according to the Coombs and Gell classification they can be type I (immediate) hypersensitivity, type II (cytotoxic) type III (immune complex mediated) or type IV (delay). Allergy to insulin is defined as an immunological response type I, and type II or III to exogenous insulin solutions occurring the 0.1% and 0.2% of the patients. PATIENTS: A 13 year old female with a 4-year history of insulin-dependent diabetes mellitus who presented hypersensitivity against recombinant DNA (rDNA) insulin manifested with urticaria and itching. We used a premedication therapy without good response and impossibility to use alternative therapy for her metabolic control, so she needed desensitization with insulin. METHODS: Skin prick testing with rapid insulin preparations 1:10 W/V dilution were positive. IgE antibodies to insulin weren't presented. IgE serum values were normal. We began the desensitization with a rapid 1:1000 UI insulin solution by intradermal route, than by subcutaneous route until reaching the accumulated doses necessary per day. During the process it appeared a papular rash and itching which were treated with an intravenous antihistaminic without troubles. RESULTS: The patient tolerated the desensitization procedure very well. For the past 14 months she has been treated uneventfully by subcutaneous administration of rDNA insulin. DISCUSSION: The desensitization against drugs is not a frequently process it only has to be used when it is impossible to substitute the treatment. Our patient showed probably hypersensitivity type 1 to insulin. However, we have to take into account the cytotoxic reaction caused by IgG or IgM antibodies or by immune complex. The desensitization finally was tolerated, 14 months after our patient accepts correctly her daily dose of human recombinant insulin. PMID- 11759254 TI - [Experience with montelukast, a leukotriene receptor antagonist, in pediatric patients with asthma]. AB - BACKGROUND: Montelukast is a specific antagonist of leukotrienes' receptors and constitutes a therapeutic option in controlling asthma. OBJECTIVES: To evaluate efficacy of montelukast in patients with persistent light asthma, persistent moderate asthma and exercise-induced asthma; to try to reduce or to eliminate doses of inhaled steroid; to reduce the use of short-action beta agonists and to assess its tolerability in pediatric patients. MATERIAL AND METHOD: 40 patients were studied, 17 female, with an age range from 4 to 11 years and a mean of 7 years. Stratification was made by GINA-established parameters. RESULTS: Steroid dose could be reduced in 88%, with definitive suspension in 66% of patients. Moreover, an improvement in reducing asthma stratification and the use of rescue drugs were registered. 62% of patients with exercise-induced asthma improved and there was a good tolerance with the same side effects. PMID- 11759255 TI - [Correlation between positive skin tests to molds, total IgE, and specific IgE using ELISA and mold cultures from the environment of the pediatric allergy patient]. AB - The aim of this study was to made a correlation between allergic symptoms, positive skin prick test to fungi, total and specific IgE and mold culture in the patient's environmental. There were included 35 children (3-16 years), with skin prick test positive to fungi. The most frequent were: Rhizopus, Aspergillus, Cladosporium and Candida. Total and specific IgE were measured with ELISA, with titers high in 77.2% and 31.4% respectively. Fungal cultures were collected from dwellings and schools. The most frequently isolated mold genera were Cladosporium, Alternaria and Penicillium in the same proportion in both places: dwellings and schools. We concluded fungi are commonly found in children's environment. PMID- 11759256 TI - [Recurrent otitis media with effusion and food allergy in pediatric patients]. AB - INTRODUCTION: Recurrent otitis media with effusion continues to be important pediatric clinical problem and is related to food allergy. OBJECTIVE: The purpose of the present investigation was to determine if the recurrent otitis media with effusion was associated to food allergy. METHODS: We reviewed medical charts from children with food allergy and otitis media with effusion for a period of three months of duration or every month for the last six months seen in an allergy clinic. Patients with anatomic abnormalities, polypous or immunologic deficiencies were excluded. Every patient was challenged with foods to which he/she was allergic in order to demonstrate cause-effect. In all patients we performed tympanometries. RESULTS: We found twenty five patients with recurrent otitis media with effusion and food allergy demonstrated by positive skin testing. The most common food found to be associated was milk, egg, beans, citrus, and tomato. The elimination of the food diet led to a significant amelioration of the otitis in 22 patients, in whom clinical and tympanometry evaluation was performed. The challenge diet with suspected offending food provoked a recurrence of the otitis problem. CONCLUSION: These results demonstrated the association between recurrent otitis media with effusion and food allergy. Therefore, all patients with recurrent otitis media with effusion should be investigated for food allergy. PMID- 11759258 TI - Children's Healthcare of Atlanta enters third wave. PMID- 11759259 TI - Content that draws healthcare consumers. AB - Consumers want content that is relevant to their own health, and then want to do something with it. Providers can obtain content relatively cheaply, but the key to turning it into something valuable is to surround it with features that the consumers can really use. PMID- 11759257 TI - [Prevalence of hiatal hernia and chronic esophagitis in adult asthmatic patients]. AB - BACKGROUND: The association among asthma, hiatus hernia, oesophagitis and gastro oesophageal reflux has been reported as etiologic factor that alters the clinical evolution of the asthma. MATERIAL AND METHODS: Prospective, longitudinal and comparative study was developed. 90 patients were incoming with persistent light and moderate asthma, of allergic etiology. By the 6 months of immune-allergic treatment the clinical answer was valued being classified in two groups: Group A: 40 patients with intermittent light asthma and group B: 50 patients with persistent severe moderate asthma. In both groups they were submitted to an endoscopy for the diagnosis of esophageal pathology, with biopsies in the 3 esophageal thirds. They registered symptoms of gastro-oesophageal reflux. RESULTS: 72 women and 28 men, age average 35.9 years. There was hiatus hernia in 33 patients, 12 of the group A and 21 of the B. Upper oesophagitis in 21 patients, 8 of the group A and 13 of the B. Symptoms of gastro-oesophageal reflux in 71 patients, 29 of the group A and 42 of the B. The association among hiatus hernia, oesophagitis and gastro-oesophageal reflux was observed in 12 patients, 2 of the group A and 10 of the B (p < 0.05). CONCLUSIONS: The association of symptoms among gastro-oesophageal reflux, hiatus hernia and upper oesophagitis, is bigger in the patients with bad answer to the anti-asthmatic treatment; they are justified to endoscopy study and biopsies of the upper oesophagus (in the group of patients with bad response and symptoms of gastro-oesophageal reflux) when 24 hours pH-monitoring is not available. PMID- 11759260 TI - Reaching out to seniors. PMID- 11759261 TI - A look at wired seniors. PMID- 11759262 TI - Influenza in the world. 1 October 2000-30 September 2001. PMID- 11759263 TI - A unique method for predicting cardiorespiratory fitness using rating of perceived exertion. AB - The purpose of this study was to develop a simple and convenient indirect method for estimating maximal oxygen uptake (VO2max) and oxygen uptake at the anaerobic threshold (VO2AT) by using workrate and a rating of perceived exertion (RPE) during a submaximal graded cycling test (GCTsubmax). One hundred and fifty-four healthy Japanese men, aged 20 to 64 years, volunteered to participate in the study. The subjects were randomly divided into two groups, a validation (V) group (n = 100) and a cross-validation (CV) group (n = 54). The V and CV groups performed a maximal cycling test and the GCTsubmax. The GCTsubmax was conducted with documentation of three categories (overall, chest, legs) of RPE, up to a rating of 15. Prediction equations of VO2max and VO2AT were developed by multiple regression analysis using data of the V group. The mean VO2max and VO2AT of the V group were 2462 +/- 484 ml.min-1 and 1349 +/- 334 ml.min-1, respectively. Correlational analyses indicated that the workrate (W) at which the legs RPE (RPElegs) reached 15 or higher was evaluated first (WRPE legs 15) together with WRPE legs 14 both yielded the highest correlation coefficients (r) with VO2max (r = 0.781) and V O2AT (r = 0.790), respectively. The developed prediction equations of VO2max and VO2AT were VO2max (ml.min-1) = 1.19 WRPE legs 15 (kgm.min-1) - 15.84 age (yr) + 13.06 weight (kg) + 1365 (R = 0.849, SEE = 261 ml.min-1) VO2AT (ml.min-1) = 1.34 WRPE legs 14 (kgm.min-1) - 5.49 age (yr) + 665 (R = 0.816, SEE = 195 ml.min-1) Results of a cross-validation analysis indicated a similar estimation (r = 0.793 and 0.853, and SEE = 240 ml.min-1 and 183 ml.min-1) compared with the above equations developed from data of the V group. Reliability coefficients of V O2max (r = 0.891) and VO2AT (r = 0.870) respectively were significant and there was no difference in the mean value between trials 1 and 2. The "RPE method" developed for estimating cardiorespiratory fitness is not only a unique indirect method but also a valid and useful tool in various settings of exercise prescription. PMID- 11759264 TI - Metabolic habituation following repeated resting cold-water immersion is not apparent during low-intensity cold-water exercise. AB - This project examined the effects of repeated, resting cold-water immersion on metabolic heat production and core temperature defence during subsequent rest and exercising immersions. Seven males undertook 15 days of cold-water adaptation, immersed to the fourth intercostal space, with cold-water stress tests (CWST) on days 1, 8 and 15 (18.1 SD 0.1 degree C: 60 min seated, followed by 30 min cycling (1 W.kg-1)), and 90-min resting immersions (18.4 SD 0.4 degree C) on each of the intervening days. Adaptation elicited an habituated thermogenic response during the rest phase of CWST3 beyond 20 min, compared to CWST1 (P < 0.05), with oxygen consumption averaging 11.15 (+/- 0.25) ml.kg-1.min-1 and 8.61 (+/- 0.90) ml.kg 1.min-1 by 50 min, for CWST1 and CWST3, respectively. During exercise, this metabolic blunting was only apparent over the first 10-min period (60-70 min). No significant differences were observed during either the rest or exercise phases of the CWSTs for oesophageal temperature (Tes). While repeated cold-water exposures produced an habituated-thermogenic response, for an equivalent drop in Tes during rest, neither this response, nor an elevated thermogenesis, were apparent during subsequent cold-water exercise. PMID- 11759265 TI - Cardiorespiratory response to low-intensity walking in water and on land in elderly women. AB - The purpose of the present study was to determine whether or not the exercise intensity of water-walking for elderly women could be accurately prescribed by heart rate data obtained during treadmill exercise on land. Six healthy female volunteers, with a mean age of 62.2 +/- 4.2 years, took part in this study. Walking on land was performed on a treadmill. Each subject completed three consecutive 4-minute walks at a progressively increasing velocity (40, 60 and 80 m.min-1), with a 1-minute rest after both the first and second walks. The room temperature and relative humidity were 24.5 +/- 0.2 degrees C and 54.8 +/- 4.0%, respectively. Walking in water was performed in a Flowmill, which is a treadmill positioned at the base of a water flume. Each subject completed three consecutive 4-minute walks at a progressively increasing belt and water-flow velocity (20, 30 and 40 m.min-1), with a 1-minute rest after both the first and second walks. The water depth was at the level of the xiphoid process of each subject. The water temperature was 30.7 +/- 0.1 degrees C. The exercise intensity at the highest workrate was equivalent to 44.2 +/- 10.3% of the heart rate reserve (HRR) during water-walking and 38.4 +/- 4.7% of the HRR during land-walking. There was a highly significant linear relationship between heart rate (HR) and oxygen uptake (VO2) during both water-walking and land-walking. The relationship between HR and VO2 in both exercise modes was similar. Thus, the relationship of HR to VO2 derived from a treadmill-graded walking test on land may be used to prescribe exercise intensity for water-walking in thermoneutral water. PMID- 11759266 TI - Age dependence of human gastrocnemius Mg2+: fitting 31P-NMR spectra using quantum mechanics-based prior knowledge. AB - The age dependence of human gastrocnemius Mg2+ concentration is demonstrated. To quantitate Mg2+ concentration, an original and accurate fitting algorithm using quantum mechanics-based prior knowledge is detailed. In a group of 28 volunteers (14 females) in the age range 5-80 years, pH, PCr/ATP and Pi/ATP values in the gastrocnemius were 7.02 +/- 0.02 pH, 4.16 +/- 0.33 and 0.13 +/- 0.02, respectively and independent of age and sex. By contrast, intracellular Mg2+ concentration (mM) decreased linearly (p < 0.05) with age (Mg2+ = 0.7803 +/- 0.0247-0.0027 +/- 0.0005 * age). No difference was found between sexes. From these results, it follows that care must be taken when comparing muscle Mg2+ data from subjects of different age. The hypothesis can be put forward that during aging insufficient intake and/or increased depletion of Mg2+ (e.g., intestinal hypoabsorption or urinary leakage) may affect the musculoskeletal system. PMID- 11759267 TI - Suppressive effects of genistein dosage and resistance exercise on bone loss in ovariectomized rats. AB - This study was designed to determine whether combined treatments with genistein dosage and moderate resistance exercise would exhibit synergistically preventive effects on bone loss following the onset of menopause. Forty-one 12 wk-old female SD rats were assigned to five groups: 1) Sham operated (Sham); 2) ovariectomized (OVX-Cont); 3) OVX received genistein (OVX-GEN); 4) OVX exercised (OVX-EXE); and 5) OVX treated with both genistein and exercise (OVX-GEN-EXE). All rats were fed a low Ca (0.1%) diet ad libitum. Daily genistein dosage was 12 mg/kg body weight. Exercising rats took 40 sets of 1-min run interspersed with 1-min rest with a 100 g weight on the back on an uphill treadmill at 20 m/min. The experimental duration consisted of the adaptation and treatment periods of 4 weeks each. Uterine weight in OVX-Cont, OVX-GEN, OVX-EXE and OVX-GEN-EXE decreased to about 15% of that in Sham (p < 0.001). The femoral BMD (mg/cm2; mean +/- SE), assessed by DEXA (Lunar), of OVX-Cont was significantly lowered to 206 +/- 5 by -9%, as compared to 226 +/- 2 of Sham (p < 0.001). The BMD of OVX-GEN, OVX-EXE and OVX GEN-EXE were 217 +/- 2, 217 +/- 2 and 222 +/- 2, respectively, and genistein dosage and resistance exercise equally increased the BMD of OVX rats by 5% (p < 0.01). Combined treatment of genistein and exercise more successfully recovered their decreased BMD by 8% (p < 0.001). BMD of the fourth lumbar vertebrae in OVX Cont was declined to 191 +/- 7 by -15%, as compared to 225 +/- 4 in Sham (p < 0.001). OVX-EXE and OVX-GEN-EXE gained the BMD by 6% to 205 +/- 4 and 203 +/- 3, respectively, as compared to that of OVX-Cont (p < 0.01). These results suggest the possibility that the combined treatment of genistein dosage and resistance exercise have more beneficial effects by acting rather independently than their separate trials on the prevention of ovx-induced bone loss in femurs. PMID- 11759268 TI - Human gastrocnemius medialis pennation angle as a function of age: from newborn to the elderly. AB - The aim of the present study was to quantify changes in human skeletal muscle pennation angle (F theta) values during growth and adult life. The human gastrocnemius medialis muscle of 162 subjects (96 males and 66 females) in the age range 0-70 years was scanned with ultrasonography. The subjects were laying prone, at rest, with the ankle maintained at 90 degrees with all muscles relaxed. F theta increased monotonically starting from birth (0 years) and reached a stable value after the adolescent growth spurt. There was a significant (p < 0.05) linear relationship between F theta and muscle thickness (TK). F theta = 0.84 (+/- 0.09) * TK + 3.15 (+/- 1.13). Human gastrocnemius medialis F theta and TK data found in the literature seem to fit the F theta-TK plot in a coherent manner, independent of the physiological or anatomical characteristics of the subject. The present findings indicate that F theta is not a constant parameter but evolves, as is the case for bone length and height, as a function of age. PMID- 11759269 TI - Providing mental health services to Arab Americans: recommendations and considerations. AB - Arab Americans are an extremely heterogeneous and frequently misunderstood group whose unique characteristics and cultural heritage have received little attention in the mental health literature. To effectively address the needs of Arab Americans, mental health professionals need to be aware of their own biases and misperceptions regarding Arab Americans, have an accurate understanding of Arab cultural and sociopolitical backgrounds, and be able to identify culturally appropriate interventions for use with Arab American clients. This article reviews common stereotyped beliefs many Americans have about Arab Americans and the negative impact these stereotypes can have on the development of a positive Arab American ethnic identity. It also provides detailed information about the cultural and sociopolitical experiences of Arab Americans and offers specific recommendations for providing culturally relevant mental health services to Arab American clients. PMID- 11759270 TI - Are empirically supported treatments valid for ethnic minorities? Toward an alternative approach for treatment research. AB - The psychological community has given considerable attention to the problem of establishing empirically supported treatments (ESTs). The authors argue that a scientific practice that discriminates against some approaches to knowledge undermines the EST's relevance for communities of color. They examine the EST project's contribution to knowledge of effective treatments for ethnic minorities by considering both how knowledge is constructed and the limits of research (e.g., external validity). Alternatives on how to best contribute to treatment research of clinical utility with diverse populations are articulated. An approach for treatment research, derived from an integration of the hypothesis testing and discovery-oriented research approaches, is presented, and recommendations to advance treatment research with ethnic minority communities are offered. PMID- 11759271 TI - Cultural value similarities and differences among Asian American ethnic groups. AB - Using data on 570 Chinese, Filipino, Korean, and Japanese American college students from 3 previous studies (1 published [B. S. K. Kim, D. R. Atkinson, & P. H. Yang, 1999] and 2 unpublished [B. S. K. Kim, 1999; E. C. Wong, B. S. K. Kim, N. W. S. Zane, I. J. Kim, & J. S. Huang, 1999]), the authors subjected 22 items constituting 6 value dimensions of the Asian Values Scale (AVS; B. S. K. Kim et al., 1999) to the following structural equation modeling procedures: confirmatory factor analysis, factorial invariance analysis, and structured means analysis. The results of confirmatory factor analysis provided support for a hierarchical factor model when this model was compared with 2 competing models. The results of factorial invariance analysis indicated that the meanings of the factors within the hierarchical model were conceived similarly among the 4 Asian American ethnic groups. On the basis of these results, a structured means analysis was conducted, revealing similarities and differences between the ethnic groups' adherence to 6 cultural value dimensions. Implications regarding psychological services for these Asian Americans are discussed, and suggestions for future research are offered. PMID- 11759272 TI - The relationship of acculturation and gender to attitudes toward counseling in Italian and Greek American college students. AB - This exploratory study examined attitudes toward professional psychological services and help provider characteristics among 232 self-identified Italian and Greek American college students in 3 Northeast colleges. Regarding general attitudes toward psychological services in the Italian American sample, women had a greater recognition of personal need for help and higher confidence in the ability of mental health professionals to meet these needs than did men. With regard to preferred counselor demographic characteristics, regardless of gender, lower acculturated Italian American students had a stronger preference for seeing an ethnically similar counselor. With the Greek American sample, there was an interaction effect between acculturation level and gender on attitudes toward services. Among the higher acculturated Greek students, women were more open regarding their personal concerns than men; however, within the lower acculturated cohort, no gender differences were found. With regard to counselor characteristic variables, and similar to Italian Americans, regardless of gender, lower acculturated Greek Americans had a stronger preference for seeing an ethnically similar counselor to discuss a personal problem. Limitations and implications for further research are noted. PMID- 11759273 TI - Gender, ethnicity, and acculturation in intergenerational conflict of Asian American college students. AB - This study examined differences in patterns of intergenerational conflict according to gender, ethnicity, and acculturation level of Asian American college students. A survey containing a measure of acculturation and intergenerational conflict was completed by 342 participants. A 2 (gender) x 5 (ethnicity) x 3 (acculturation) multivariate analysis of variance for the 3 subscales of the Intergenerational Conflict Inventory revealed significant F values for all 3 main effects, but none for the interactions. On the subscale of Dating and Marriage, male students reported less conflict than female students, and Japanese Americans reported less conflict than Chinese, Filipino, Korean, and Southeast Asian Americans. On the subscale of Family Expectations, Japanese Americans also reported less conflict than Koreans and Southeast Asians. On both of these and a 3rd subscale of Education and Career, the acculturated group reported lower conflict than both the low-acculturated and bicultural groups. The implications of these findings for research and practice are discussed. PMID- 11759274 TI - Brief therapy of civil war-related trauma: a case study. AB - The incidence of posttraumatic stress disorder is widespread among refugees who have been exposed to violence or torture. Many families struggle with side effects of this condition, such as recurrent nightmares, flashbacks, emotional detachment, and difficulty trusting people. Some unwittingly become involved in a pattern of alcoholism, family violence, and somatic illness that is rooted in traumatization. Service providers must often struggle with overwhelmed clients whose multiple needs make long-term therapy impractical. Thus, brief treatment appears to be especially well suited to this population. This article describes a case study using short-term psychotherapy (10 to 20 sessions) that aims to restore refugees who are in reasonable emotional health to their premorbid level of functioning. A 4-stage treatment process involving specific tools is described, and the case study is used as an illustration. Contraindications for time-limited therapy are also outlined. PMID- 11759275 TI - Changing concepts of dietary fiber: implications for carcinogenesis. AB - The dietary fiber (DF) hypothesis suggested that DF, as plant cell walls, protected against colorectal cancer. The implicit assumption in much historic literature was that the readily analyzed and quantified nonstarch polysaccharide (NSP) component was critical in cancer protection. However, the presence of polymeric phenolic components such as lignin or suberin has profound effects on the physicochemical properties of the cell walls and largely determines their physiological properties in humans. In certain groups of food plants, degradation of cell walls that contain neither lignin nor suberin releases ferulic acid and other hydroxycinnamic acids. These acids have antioxidant, antimutagenic, and other anticancer effects, including modulation of gene expression and immune response. Reexamination of literature on cancer protection suggests that plant cell walls containing significant amounts of phenolic components may be the most likely to protect against cancer. In the last 30 years, the definition of DF has been incrementally expanded to incorporate NSP extracted from plant cell walls and from sources other than plant cell walls, then resistant starch, and most recently nondigestible oligosaccharides. On the early definitions, increased consumption of DF could only be achieved by increasing the intake of whole grains, brans, or other food plant material that would increase the intake of plant cell walls containing significant amounts of phenolic components. However, the new definitions make it possible to increase "dietary fiber" without consuming any such materials. We suggest that this could have negative connotations for cancer risk in human populations. PMID- 11759276 TI - Trans-fatty acids and colon cancer. AB - Trans-fatty acids have been hypothesized to be carcinogenic, although there are limited data in humans testing this hypothesis. In this study, we examine the association between trans-fatty acids and colon cancer using data from a case (n = 1,993)-control (n = 2,410) study conducted in Utah, Northern California, and Minnesota. Dietary data were collected using a detailed diet history questionnaire, and nutrient values were generated from the Nutrition Coordinating Center nutrient database. After adjustment for other variables, including age at diagnosis, body size, physical activity, aspirin and/or nonsteroidal anti inflammatory drug (referred to collectively as NSAIDs) use, energy intake, and dietary fiber and calcium, we found a weak association in women [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-2.0] but not in men (OR = 1.2, 95% CI = 0.9-1.7); no increased risk was observed for the cis form of the fatty acids. For men and women, slightly stronger associations were observed in those > or = 67 years of age (OR = 1.4, 95% CI = 0.9-2.1 for men; OR = 1.6, 95% CI = 1.0-2.4 for women). Those who did not use NSAIDs were at a 50% greater risk of developing colon cancer when they consumed high levels of trans-fatty acids. Women who were estrogen negative, i.e., postmenopausal not taking hormone replace therapy, had a twofold increase in risk from high levels of trans-fatty acids in the diet, while women who were estrogen positive did not experience an increased risk of colon cancer, regardless of level of trans-fatty acids consumed. We believe that these data have important public health implications. It seems prudent to avoid consuming partially hydrogenated fats, since no increased risk was observed for the cis form of fatty acids, while suggestions of increased risk from trans-fatty acids exist for subsets of the population. PMID- 11759277 TI - Tea consumption and the risk of colorectal cancer in Sweden. AB - The association between tea drinking and colorectal cancer risk remains unclear. The evidence for black tea is sparse but may indicate an increased risk with regular use. Because black tea is a common beverage in many populations, the significant twofold increased risk of colon cancer recently reported from a large prospective cohort of male Finnish smokers is disconcerting. Using Cox proportional hazards models to estimate relative risks, we examined this association in a large, population-based prospective cohort study in Sweden. During an average 9.6 years of follow-up of our cohort of 61,463 women (588,270 person-yr), we observed 460 incident cases of colorectal cancer (291 colon, 159 rectal, and 10 with both colon and rectal cancer). We observed no association between tea consumption and combined colorectal cancers in age- or multivariate adjusted models. With the use of collapsed exposure categories, the multivariate adjusted relative risk for the highest exposure (> or = cups/day) compared with the lowest (never or seldom) was 0.97 (95% confidence interval = 0.63-1.48, p for trend = 0.34). Examining the association by cancer subsite, we observed no association between tea consumption and proximal, distal, or combined colon cancers. We did, however, observe a nonsignificant positive association with rectal cancers, which became stronger and statistically significant among women > or = 65 years of age at baseline. Our data do not support the strong, dose dependent positive association with colon cancer found in the Finnish study. PMID- 11759278 TI - Whole grain intake and incident endometrial cancer: the Iowa Women's Health Study. AB - We examined whether there is an association between whole grain intake and incident endometrial cancer and whether the association varied by use of hormone replacement therapy. The study included 23,014 Iowa women, aged 55-69 years in 1986. A mailed food frequency questionnaire was used to estimate grain intake, hormone replacement therapy use, and other cancer risk factors. Cancer incidence from 1986 to 1998 was also collected. In analyses stratified by hormone replacement therapy use, an inverse association between whole grain intake and endometrial cancer was observed among never-users of hormone replacement therapy (p for trend = 0.05). Never-users in the highest quintile of whole grain intake were 0.63 times as likely to develop endometrial cancer as those in the lowest quintile of whole grain intake (95% confidence interval = 0.39-1.01). Among hormone replacement therapy users, no association between whole grain intake and endometrial cancer was evident. There was no statistically significant association between whole grain intake and incident endometrial cancer when users of hormone replacement therapy and nonusers were analyzed together. There also was no association between refined grain intake and endometrial cancer. Whole grain intake may protect against endometrial cancer among never-users of hormone replacement therapy. PMID- 11759279 TI - Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire. AB - This report describes the development and validation/calibration of a structured food frequency questionnaire for use in a large-scale cohort study of diet and health in Chinese men and women aged 45-74 years in Singapore, the development of a food composition database for analysis of the dietary data, and the results of the dietary validation/calibration study. The present calibration study comparing estimated intakes from 24-hour recalls with those from the food frequency questionnaires revealed correlations of 0.24-0.79 for energy and nutrients among the Singapore Chinese, which are comparable to the correlation coefficients reported in calibration studies of other populations. We also report on the nutritional profiles of Singapore Chinese on the basis of results of 1,880 24 hour dietary recalls conducted on 1,022 (425 men and 597 women) cohort subjects. Comparisons with age-adjusted corresponding values for US whites and blacks show distinct differences in dietary intakes between the Singapore and US populations. The Singapore cohort will be followed prospectively to identify dietary associations with cancer risk and other health outcomes. PMID- 11759280 TI - Dietary calcium consumption and astrocytic glioma: the San Francisco Bay Area Adult Glioma Study, 1991-1995. AB - Previous studies suggest an association between calcium consumption and glioma risk. In the present study, we compare consumption of calcium and other dairy components and foods (cholesterol, fat, protein, calories, milk, and cheese) of 337 astrocytic glioma case patients with 450 controls from the San Francisco Bay Area Adult Glioma Study, 1991-1995. We use unconditional logistic regression models to estimate odds ratios (ORs) by gender controlling for age, education, and income. A statistically significant inverse association [p (trend) = 0.05] was observed for dietary calcium intake for women only [OR = 0.49, 95% confidence interval (CI) = 0.24-1.03 for highest vs. lowest quartile of consumption]. In addition, we observed elevated ORs for highest vs. lowest quartiles of cholesterol intake among women and men (OR = 2.07, 95% CI = 1.00-4.28 and OR = 1.75, 95% CI = 0.92-3.31, respectively). Calcium may exert a protective effect through its known roles in apoptosis, DNA repair, and inhibition of parathyroid hormone production. Recent evidence suggests that parathyroid hormone may influence growth and dedifferentiation of astrocytoma cells. Finally, circulating estradiol might directly stimulate intestinal absorption of calcium and may therefore explain why the inverse association of calcium intake and glioma is confined to women. PMID- 11759281 TI - Role of dietary habits in the development of esophageal cancer in Assam, the north-eastern region of India. AB - The etiology of esophageal cancer remains largely unknown. In recent years, the role of dietary habits in the development of esophageal cancer has received much attention. Prevalence of esophageal cancer in Assam is highest among all the states of India. To identify the possible risk factors, a hospital-based case control study was conducted with 502 cases and 1,004 controls. "Kalakhar," a unique and locally made food item, has emerged as a significant risk factor (odds ratio = 8.0, 95% confidence interval = 5.1-11.5, p < 0.001). Consumption of very spicy foods, hot foods and beverages, a diet containing high amounts of chili, and leftover food was positively associated with the risk of esophageal cancer. Green leafy vegetables and fruits were protective for esophageal cancer. The risk factors associated with consumption of locally prepared food items, e.g., kalakhar, and some dietary practices did not decrease, even after adjustments with different confounding factors. However, further studies are required to conclusively implicate these factors in causation of esophageal cancer. PMID- 11759282 TI - Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss. AB - The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C-reactive protein) in male patients (n = 40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r = 0.390, p < 0.05), extent of reported weight loss (r = -0.492, p < 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r = 0.686, p < 0.001), and log10 C-reactive protein concentrations (r = -0.545, p < 0.001). On multiple regression analysis, the percent predicted total body potassium and log10 C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r2 = 0.626, p < 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer. PMID- 11759283 TI - Effect of varying dietary fat levels on rat growth and oxidative DNA damage. AB - Dietary fat has previously been shown to have somewhat complicated relationships to levels of oxidative stress in rats. In this study, we examined the effects of five different dietary fat intakes on levels of oxidative DNA damage in rats. Animals fed diets containing 3%, 5%, 10%, or 15% corn oil had body weights that were similar after 20 weeks. Animals fed a 20% fat diet, however, had significantly higher mean body weight than any other group. Levels of 5 hydroxymethyl-2'-deoxyuridine, one marker of oxidative DNA damage, had different relationships to dietary fat in blood and mammary gland. In blood, levels increased with dietary fat levels, and the highest levels were observed with the 20% fat diet (65% higher levels than with the 3% fat diet). In mammary gland, a plateau-type effect was observed, with maximal levels of oxidative DNA damage being obtained using 10% fat (representing a 68% increase relative to the 3% fat diet). This could be a result of induction of compensatory mechanisms in response to a high-fat diet in mammary gland but not in the short-lived nucleated blood cells. Oxidative DNA damage levels in blood thus appear to be a marker of dietary fat intake. In mammary gland, however, levels of DNA damage are consistent with previously observed promotional effects of dietary fat on mammary gland tumorigenesis at lower levels of fat intake with little or no incremental promoting effects at higher levels of fat intake. PMID- 11759284 TI - Effect of types and amount of dietary fat during the initiation phase of hepatocarcinogenesis. AB - The effects of various levels of corn oil and lard fed during the initiation stage of azoxymethane (AOM)-induced hepatocarcinogenesis were studied in male Fischer 344 rats. The animals were fed diets containing 5%, 13.6%, and 23.5% corn oil or lard two weeks before, during, and until one week after injections of AOM (15 mg/kg body wt s.c.) once weekly for two weeks. One week after AOM treatment, groups of animals fed the 13.6% and 23.5% corn oil or lard diet were transferred to their respective 5% corn oil or lard diet and fed these diets until the termination of the study (34 wk). Immunohistochemical staining of glutathione S transferase placental form was performed in the liver, and the number of glutathione S-transferase placental form-positive foci was determined. Density, average area, and unit area of foci were significantly inhibited in the animals fed the 13.6% and 23.5% lard diets compared with those fed the 13.6% and 23.5% corn oil diets. These results indicate that the effect of dietary fat during the initiation phase of AOM-induced hepatocarcinogenesis depends on the type of fat and its fatty acid composition. Additionally, the enhancing effect of a corn oil diet in hepatocarcinogenesis is mainly present during the initiation phase of carcinogenesis compared with a lard diet. PMID- 11759285 TI - Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice. AB - Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor alpha knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ER alpha KO mice consuming less than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed. PMID- 11759286 TI - Control of rat mammary epithelium proliferation by conjugated linoleic acid. AB - Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9, t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of > 90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status. PMID- 11759287 TI - Effects of green tea on colonic aberrant crypt foci and proliferative indexes in rats. AB - The present study was designed to investigate the effect of green tea on 1,2 dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation in Wistar rats. Forty-five male weanling Wistar rats were randomly divided into three groups. Rats in Group 1 were injected with DMH (20 mg/kg s.c.) once a week for 10 weeks. Animals in Group 2 received 2% green tea water extract as the sole source of drinking fluid in addition to the same treatment used for Group 1. Group 3 was the negative control group. Animals were killed at the end of Week 16 after the first DMH treatment. ACF were formed in animals in their DMH-treated groups at the end of Week 16. Group 2 had fewer ACF than Group 1. Compared with the positive control group, proliferating cell nuclear antigen labeling index, silver stained nucleolar organizer regions, and ras-p21 expression were significantly reduced in Group 2. It was concluded that green tea drinking inhibited ACF formation in rats, and such effects may be related to the suppression of cell proliferation in the intestinal crypts. PMID- 11759288 TI - Vitamin A and all-trans and 9-cis retinoic acids inhibit cell proliferation during the progression phase of hepatocarcinogenesis in Wistar rats. AB - The effects of vitamin A and all-trans and 9-cis retinoic acids on the progression phase of hepatocarcinogenesis were evaluated in this study. For this purpose, male Wistar rats were first submitted to the resistant hepatocyte model of carcinogenesis (diethylnitrosamine for initiation and 2-acetylaminofluorene for selection/promotion). Ten months after initiation, the animals were distributed into four groups and treated by gavage, every other day and during eight weeks, with corn oil (control group), vitamin A (10 mg/kg of body wt), all trans retinoic acid (10 mg/kg body wt), or 9-cis retinoic acid (10 mg/kg body wt). After this period, the animals were killed one hour after intraperitoneal administration of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg body wt). At the time of sacrifice, liver samples were collected for histopathological (hematoxylin eosin) examination and immunohistochemical detection of glutathione S-transferase and BrdU, as well as for analysis of retinol and retinoic acid concentrations. Histopathological examination showed the lowest incidence of hepatocarcinomas in vitamin A-treated animals. Moreover, groups treated with retinoids demonstrated lower hepatic BrdU labeling indexes in the neoplastic lesions, as well as in their respective surrounding tissues, than controls. Thus vitamin A and all-trans and 9-cis retinoic acid strongly inhibited cell proliferation when administered during the progression phase of hepatocarcinogenesis. Therefore, the anticarcinogenic effects that have been attributed to these retinoids could be partially related to their capacity of inhibiting in vivo cell proliferation. PMID- 11759289 TI - Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model. AB - Cancers of the colon and breast are two of the most prevalent cancers in developed countries. The present experiments were conducted to determine the influence of several dietary doses of grape seed proanthocyanidins on 7,12 dimethylbenz[a]anthracene-induced mammary tumorigenesis and azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) formation in a dual-organ tumor model. In addition, the effects of the grape seed proanthocyanidins on liver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities and on colonic ornithine decarboxylase activity were examined to determine possible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhibition of AOM induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feeding the grape proanthocyanidins resulted in no significant effect on the activity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. This lack of action on mammary tumorigenesis in part may be due to lack of effect of dietary proanthocyanidins on the liver carcinogen-metabolizing enzymes cytochrome P-450 1A and glutathione S-transferase. These results indicate that grape polyphenolics warrant further evaluation as potential colon cancer chemopreventive agents. PMID- 11759291 TI - Study of N-nitrosomorpholine-induced DNA strand breaks in Caco-2 cells by the classical and modified comet assay: influence of vitamins E and C. AB - We have studied the genotoxic effects of the well-known heterocyclic liver carcinogen N-nitrosomorpholine (NMOR), an N-nitroso compound, which was prepared in our laboratory by nitrosation of the secondary amine morpholine with NaNO2. NMOR induced DNA strand breaks in human colon carcinoma Caco-2 cells. The concentration-dependent DNA-damaging effects of NMOR were proved by the comet assay. We further characterized DNA strand breaks induced by NMOR as follows: 1) We pretreated cells with vitamins E and C, which are able to eliminate oxidative DNA damage. 2) We varied the pH of the comet assay (12.1 and 13). In general, alkali-labile sites are stable until pH is raised to 12.5. 3) We used the site specific repair enzymes exonuclease III and formamidopyrimidine-DNA glycosylase in the modified comet assay. Results showed that NMOR-induced DNA strand breaks have their origin exclusively in alkali-labile sites. Nevertheless, vitamins E and C decreased the level of DNA strand breaks. These results showed that antioxidants may have biological activities other than free radical scavenging that relate to their cancer-prevention properties. Our conceptions about reduction of NMOR-induced DNA lesions in Caco-2 cells by vitamins E and C are presented in this work. PMID- 11759290 TI - Modulation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutation in the cecum and colon of big blue rats by conjugated linoleic acid and 1,2-dithiole 3-thione. AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potent mutagen and suspected human carcinogen present in cooked protein-rich food. It preferentially induced colon tumors in male rats and mammary tumors in female rats. In the present study, the in vivo antimutagenic efficacy of two dietary compounds, conjugated linoleic acid (CLA) and 1,2-dithiole-3-thione (DTT), against PhIP was explored using 1acI transgenic Big Blue rats. Five- or six-week-old male Big Blue rats were fed a diet containing CLA (0.5%, wt/wt) or DTT (0.005%, wt/wt) starting one week before exposure to 200 ppm PhIP for 61 days. PhIP treatment induced a approximately 8- to 16-fold increase in the mutation frequency (MF) in the colon. The induced MF was significantly lower in the cecum than in the proximal and distal colon (approximately 52 x 10(-5) vs. 100 x 10(-5), p < 0.008). CLA and DTT significantly reduced the PhIP-induced MF in the distal colon (p < 0.05) by 14% and 24%, respectively. The frequency of -1 frameshift mutations was lower in the distal colon of CLA- or DTT-treated rats. This protective effect was not observed in the cecum or in the proximal colon. In contrast, the PhIP-induced MF in the cecum (specifically, the frequency of -1 frameshifts and GC-->TA transversions) was elevated by 43% after treatment with CLA. In conclusion, CLA and DTT modulate PhIP-induced mutagenesis in a tissue-specific manner, and different modulation pathways are employed by CLA and DTT. PMID- 11759292 TI - Acyclic carotenoids and their oxidation mixtures inhibit the growth of HL-60 human promyelocytic leukemia cells. AB - Lycopene has been known as a potential food component for cancer prevention, since tomato consumption was shown to be associated with reduced risk of certain cancers. We used HL-60 cells as a model of cancer cells to investigate whether acyclic carotenoids, such as phytoene, phytofluene, and zeta-carotene present in tomatoes, other than lycopene, as well as oxidation mixtures of these carotenoids, are potentially involved in the cancer-preventive action of tomatoes. When HL-60 cells were grown in the carotenoid-supplemented medium for 120 hours, zeta-carotene and phytofluene at 10 microM inhibited cell growth to 3.7% and 22.6% of the growth in control culture, respectively, although they were extremely unstable in the culture medium. The oxidation mixture of each carotenoid, which was prepared by incubation in toluene at 37 degrees C for 24 hours, more strongly inhibited cell growth than each intact carotenoid. The growth inhibition by lycopene was remarkably enhanced by its oxidation before supplementation to the medium. Phytofluene, zeta-carotene, and the oxidation mixture of lycopene induced apoptosis in HL-60 cells during incubation for 24 hours. The addition of alpha-tocopherol to the medium did not eliminate growth inhibition by the oxidation mixture of lycopene. These results suggest that the acyclic carotenoids inhibit cell growth through apoptosis induction and that oxidation products of the carotenoids participate in the growth inhibition. PMID- 11759293 TI - Antioxidants prevent the lymphocyte DNA damage induced by PMA-stimulated monocytes. AB - Oxidative stress has been related to several degenerative diseases such as cancer and coronary heart disease. Reactive oxygen species can damage different cellular macromolecules, including DNA, which is directly responsible for mutation and carcinogenesis. In this study, monocytes that were activated by phorbol 12 myristate 13-acetate (PMA) were coincubated with lymphocytes, and the DNA damage was measured by single-cell gel electrophoresis (comet) assay. Stimulation of monocytes with PMA activates the "respiratory burst," which evokes DNA damage in lymphocytes. The extent of the damage is related to the concentration of monocytes and the exposure time. Exogenous addition of superoxide dismutase did not prevent the DNA damage, which suggests that superoxide ions are not directly responsible for the damage. Partial protection was observed when catalase was included (60% protection), which indicates that other reactive species, in addition to H2O2, are responsible for the damage. In this system, the protective activity of natural antioxidants at different concentrations was also investigated. After coincubation of PMA-activated monocytes with lymphocytes in the presence of each antioxidant for one hour at 37 degrees C, the lymphocyte DNA damage was determined. All the compounds protected the lymphocytes to a certain degree, with a maximum effect at different concentrations: 41% protection with 1 microM ascorbic acid, 55% protection with 40 microM alpha-tocopherol, 50% protection with 3 microM beta-carotene, and 56% protection with 5 microM quercetin. On the basis of these results, we maintain that this "ex vivo model," more closely related to physiological conditions, could be used to test the antioxidant activity of different compounds. PMID- 11759295 TI - Beta-carotene uptake and bioconversion to retinol differ between human melanocytes and keratinocytes. AB - beta-Carotene is one of the carotenoids that has been considered to play a role in the natural defense against ultraviolet-induced skin cancer. It is not known whether epidermal cells are able to accumulate beta-carotene and, subsequently, convert it to vitamin A. We used normal cultured human keratinocytes and melanocytes to study the uptake, and possible bioconversion to retinol, of authentic or [14C]beta-carotene. The uptake was much higher in melanocytes than in keratinocytes, corresponding to a fivefold difference in the intracellular fraction after two days of incubation. An increased level of cellular retinol was noted after one day of beta-carotene incubation. The conversion of [14C]beta carotene to [14C]retinol peaked at 24 hours of incubation in keratinocytes and melanocytes. The results suggest that beta-carotene can function as a local supply of vitamin A in the skin and that melanocytes are especially likely to store beta-carotene. PMID- 11759294 TI - Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. AB - Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators. PMID- 11759296 TI - When the foxes watch the henhouse. PMID- 11759297 TI - Readers clarify and expand on cancer-related patient education. PMID- 11759298 TI - What are potential liability issues of conducting sentinel lymph node biopsy off study? PMID- 11759299 TI - Hand-foot syndrome. PMID- 11759300 TI - Advanced practice issues: results of the ONS Advanced Practice Nursing survey. AB - PURPOSE/OBJECTIVES: To ascertain the critical issues in current advanced practice nurse (APN) roles in oncology. DESIGN: Descriptive. SETTING: National. SAMPLE: 368 Oncology Nursing Society (ONS) APNs in oncology practice. METHODS: Subjects completed an 11-page self-administered questionnaire comprised of 62 multiple choice and open-ended questions. Subjects were asked to identify level of importance for ONS to address selected issues in each section. MAIN RESEARCH VARIABLES: Demographic information and APN issues regarding practice, outcomes, prescriptive authority, reimbursement, education, continuing education, licensure and certification, legislation, and challenges facing oncology APNs. FINDINGS: The majority of APNs were nurse practitioners working in a hematology/oncology practice in an urban setting providing direct patient care. Priority practice issues were lack of agreement among state boards of nursing related to privileges, lack of understanding of the role by patients and healthcare professionals, and lack of an APN definition. Important APN outcomes were symptom management, quality of life, patient/family satisfaction, and cost of care. Priority educational topics were oncology disease management, pharmacology, advanced physical assessment, and reimbursement. Challenges facing oncology APNs were lack of an APN definition, reimbursement issues, documentation of outcomes, prescriptive authority, variance in education, merging of current roles, certification, loss of cancer specialty, and second licensure. CONCLUSIONS: Numerous APN issues continue to be unresolved. APN outcomes research is needed to validate the oncology APN role in cancer care. IMPLICATIONS FOR NURSING PRACTICE: Survey results and specific recommendations have been forwarded to the ONS Steering Council and Board of Directors for implementation decisions. PMID- 11759301 TI - Struggling with paradoxes: the process of spiritual development in women with cancer. AB - PURPOSE/OBJECTIVES: To examine the process of spiritual development in women diagnosed with cancer within five years of initial treatment. DESIGN: Exploratory, qualitative. SETTING: Outpatients in the mid-central and southwestern United States. SAMPLE: 10 Caucasian women, ages 45-70, who completed initial treatment, were not undergoing treatment for recurrence, and were within five years of diagnosis for breast or ovarian cancer or non-Hodgkin's lymphoma. METHODS: Data collected during two semistructured interviews, coded and analyzed using grounded theory techniques. Frame of reference--symbolic interactionism. MAIN RESEARCH VARIABLES: Developmental processes of spirituality; responses to diagnosis, treatment, and survival of cancer. FINDINGS: Diagnosis of cancer threatened the meaning of the women's lives, resulting in a sense of disintegration. This problem was resolved through the basic social psychological process of Struggling With Paradoxes, a three-phase process of Deciphering the Meaning of Cancer for Me, Recognizing Human Limitations, and Learning to Live with Uncertainty. In phase I, the paradoxes focused on the possibility of death, distress, vulnerability, and maintaining connection. In phase II, the paradoxes involved confronting death, asking difficult questions, and letting go of ultimate control of their lives. In phase III, the paradoxes centered on uncertainty, redefining meaning, and identifying spiritual growth. Reintegration occurred over time, although when threatened by the possibility of recurrence, disintegration resurfaced for a time. CONCLUSIONS: Findings emphasize not only the importance of spirituality, but also that spiritual experience is individualized and developmental in nature. Spiritual growth occurs over time following the diagnosis of cancer and is not necessarily related to age. IMPLICATIONS FOR NURSING PRACTICE: Spiritual concerns may be painful for patients to address; spiritual caregiving requires an acknowledgment of need by the woman with cancer and a caring, sensitive caregiver. Nurses should be aware of the phases of spiritual development so that interventions can be designed to address individual needs that may vary over time. PMID- 11759302 TI - Oncology Nursing Society Workforce Survey. Part I: Perceptions of the nursing workforce environment and adequacy of nurse staffing in outpatient and inpatient oncology settings. PMID- 11759303 TI - Understanding anticipatory nausea. AB - PURPOSE/OBJECTIVES: To address the concept of anticipatory nausea within the theoretical framework of classical conditioning. DATA SOURCES: Published articles, book chapters. DATA SYNTHESIS: Although classical conditioning explains much in the development of anticipatory nausea, other factors also are at work. Preventing this phenomenon is necessary because it is difficult to treat and control once it develops. CONCLUSIONS: Nurses are in a position to identify patients at highest risk for developing anticipatory nausea and implement interventional strategies to prevent/minimize it. IMPLICATIONS FOR NURSING PRACTICE: Many aspects of anticipatory nausea have not yet been researched well. Nurses must study how anticipatory nausea develops and interventions that can be used to reduce its prevalence. PMID- 11759304 TI - Understanding opioid tolerance in cancer pain. AB - PURPOSE/OBJECTIVES: To review opioid tolerance in chronic cancer pain, define the phenomenon and its scope, review physiologic mechanisms, and discuss clinical strategies to identify and manage this complex issue. DATA SOURCES: Review articles, case studies, original research, and published guidelines. DATA SYNTHESIS: Novel therapies to prevent/reverse tolerance are being investigated with a possible future role for N-methyl-d-aspartate antagonists. CONCLUSIONS: Greater nursing research is needed to identify patient risk factors for tolerance development and clinical measurement of the phenomenon. Understanding cellular mechanisms for tolerance may contribute to better management. IMPLICATIONS FOR NURSING PRACTICE: Nursing knowledge of tolerance is important to provide the basis for accurate patient assessment, education, and pain management. PMID- 11759305 TI - Developing community-academic partnerships to enhance breast health among rural and Hispanic migrant and seasonal farmworker women. AB - PURPOSE/OBJECTIVES: To examine effective strategies for building community academic partnerships for the promotion of breast cancer education and outreach among rural and Hispanic migrant and seasonal farmworker women, mostly from Mexican descent. DATA SOURCES: Published research and education articles and books, community-education models, personal experiences, and community key informant feedback. DATA SYNTHESIS: Effective community partnerships for enhanced education and outreach include a framework based on a network of partners with common goals, communication processes based on trust, and bilingual/bicultural and culturally competent staff. CONCLUSIONS: A sustainable community partnership can be achieved through systematic but flexible approaches to community planning. Involvement of community members in the development and implementation of education and screening activities helps ensure that community needs are met. Relationships based on mutual respect are key. IMPLICATIONS FOR NURSING PRACTICE: Nurses can act as catalysts through community capacity building to create community-academic partnerships to reach medically underserved populations with cancer screening, outreach, and education through the delivery of strategies that are based on common goals. PMID- 11759306 TI - PRISM: Priority Symptom Management Project phase I: assessment. AB - PURPOSE/OBJECTIVES: To provide an overview of the process, goals, and outcome recommendations from the assessment phase of the Oncology Nursing Society's Priority Symptom Management (PRISM) project and to provide the foundation for a series of evidence-based practice and qualitative systematic review articles generated from the first phase of PRISM. DATA SOURCES: Published articles, abstracts, and books; computerized databases; nonpublished research; personal communications; and proceedings of the PRISM summit meeting. DATA SYNTHESIS: Symptom management is a key component in quality cancer care. The assessment phase of PRISM yielded systematic reviews with an evidence-based framework to evaluate key symptoms, developed a framework for teaching and evaluating other symptoms, and recommended future ONS initiatives. CONCLUSIONS: Outcome recommendations from the PRISM summit targeted practice; professional and public education; research; and health policy. IMPLICATIONS FOR NURSING PRACTICE: These activities provide background for subsequent evidence-based practice and qualitative systematic review articles that will focus on cancer symptom management. PMID- 11759307 TI - Research review of the supportive care needs of spouses of women with breast cancer. AB - PURPOSE/OBJECTIVES: To conduct an integrative review of the research describing the needs of spouses of women with breast cancer for direction in planning nursing interventions to meet their supportive care needs. DATA SOURCES: Published articles and bibliographies from pertinent articles. DATA SYNTHESIS: A base of knowledge exists regarding the emotional and psychosocial needs of spouses of women with breast cancer. Less is known about their spiritual, practical, and physical needs. Very little research has explored nursing interventions and supportive care needs. CONCLUSIONS: Definite knowledge gaps exist regarding the needs of spouses of women with breast cancer. More research is required to develop and evaluate interventions that focus on these needs. IMPLICATIONS FOR NURSING PRACTICE: A diagnosis of breast cancer is a distressing time for both women and their spouses. Ongoing research and the development of interventions are necessary to help spouses cope with the stress throughout the illness so that they may support their wives. PMID- 11759308 TI - Satisfaction versus dissatisfaction with venous access devices in outpatient oncology: a pilot study. AB - PURPOSE/OBJECTIVES: To examine outpatient oncology satisfaction/dissatisfaction with venous access devices (VADs), identify positive and negative experiences, and determine their overall effect on quality of life. DESIGN: Descriptive. SETTING: Outpatient oncology clinic in the United States. SAMPLE: Convenience sample of 24 patients who had a VAD and were receiving outpatient chemotherapy treatments. METHODS: Consecutive patients meeting study criteria were invited to complete a two-page questionnaire during their clinic visit. MAIN RESEARCH VARIABLES: VAD, satisfaction, dissatisfaction, quality of life. FINDINGS: Patients were extremely happy with VADs. The top three benefits were (a) decreased pain compared to venipuncture, (b) the need for fewer needlesticks, and (c) quicker blood draws for laboratory analysis. Negative experiences were infrequent, but 29% of subjects cited monthly heparinization, sleep disturbances, and site soreness following chemotherapy treatments. Overall, 92% stated that the VAD had improved their quality of life. CONCLUSIONS: Chemotherapy outpatients were extremely happy with their VAD, found many benefits, and stated that it improved their quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to support the use of VADs early with patients receiving multiple chemotherapy treatments on an outpatient basis. Research and education need to continue regarding heparinization and discuss interventions to reduce site soreness and sleep disturbances. PMID- 11759309 TI - Effects of acute exercise on state anxiety in breast cancer survivors. AB - PURPOSE/OBJECTIVES: To examine the effects of an acute bout of exercise on state anxiety in breast cancer survivors. DESIGN: A two-group (high and low state anxiety) by two-time (pre- and postexercise) mixed factorial design. SETTING: Exercise physiology lab at the University of Alberta. SAMPLE: 34 stage I or II breast cancer survivors ranging in age from 39-65 (X = 50.50; SD = 6.62). METHODS: Participants completed the State Anxiety Inventory prior to and five minutes following an acute bout of exercise. MAIN RESEARCH VARIABLES: State anxiety. FINDINGS: A main effect resulted for group (p < 0.01) and time showing that state anxiety significantly decreased from pre- to postexercise (p < 0.03). Group by time interaction showed that state anxiety for the low state anxiety group did not change from pre- to postexercise (p > 0.05); however, state anxiety significantly decreased in the high state anxiety group (p < 0.03). CONCLUSION: Acute exercise may be an effective intervention in reducing state anxiety in breast cancer survivors, especially those with high state anxiety. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should be aware that in addition to other traditional anxiolytic therapies (e.g., relaxation therapy) commonly prescribed, acute exercise is an effective method for reducing state anxiety in breast cancer survivors. PMID- 11759310 TI - Asthma intervention put to the test with inner-city kids. PMID- 11759311 TI - New screening procedure signals risk of CVD at earlier stage. AB - Begin preventive treatment for CVD before it has a chance to do damage. How? With an innovative screening tool that can non-invasively gauge the elasticity of the small and large arteries--an accepted early marker for CVD. On the market since it was approved by the FDA earlier this year, physicians and managed care organizations have already begun to use the new tool, and hopes are high that it can revolutionize the way patients are screened for this deadly and costly disease. PMID- 11759312 TI - Nationwide effort targets earlier diagnosis and treatment for HIV. AB - Consider strategies for earlier detection of HIV. New research suggests that a large percentage of patients testing positive for HIV have already progressed to full-blown AIDS at the time of diagnosis. Even more disturbing is evidence that there are clinical clues pointing toward the need for an HIV test long before many of these patients are being diagnosed. Delayed diagnosis translates into further transmission of the condition as well as higher treatment costs. Consequently, a new coalition being spearheaded by Kaiser is now taking steps intended to make sure that clinicians and patients better recognize the early tip offs to possible HIV. PMID- 11759313 TI - DM programs and preventive care get new respect in OH initiative. AB - A physician-friendly approach to prevention and DM. Physicians have long complained that they are not being reimbursed to carry out many of the preventive functions often required of them by various payers. As a result, many would argue that DM efforts often suffer from a lack of provider enthusiasm and support. To get around this problem, an innovative initiative in Ohio is attempting to give physicians a greater voice in how DM efforts are carried out, and to reward them for providing certain non-traditional preventive services. The large employers backing this effort are hoping that better preventive care and DM will translate into lower health care costs over the long term. PMID- 11759314 TI - [Monitoring the depth of anesthesia: the quest for the Holy Grail...]. PMID- 11759315 TI - [Acute severe pain in emergencies. The key for efficient analgesia]. AB - OBJECTIVE: To measure severe acute pain (SAP) frequency, to describe SAP management and to bring to view the conditions of analgesia success in emergency medicine. DESIGN: Multicentre prospective survey: 7 days in Emergency Departments (ED), 30 days in Mobile Intensive Care Units (MICU). Multivariate analysis to measure the independent effect on pain relief of factors identified by Chi squared test. SETTING: All of 6 ED and 8 MICU of a French region. PATIENTS: Over 15 years of age. MAIN OUTCOME MEASURES: Pain intensity was assessed with Visual Analog Scale (VAS) before and after ED or MICU management. SAP group (defined by initial VAS score > 40 mm) was analyzed for pain relief (defined by final VAS score < or = 40 mm). Influence on pain relief through pain aetiology, initial pain intensity, treatment delay and opioid use was analyzed. RESULTS: 1,082 fulfilled medical forms for 3,419 eligible patients. SAP frequency was estimated 36% (CI95 = 34-38%) in ED and 29% (CI95 = 25-33%) in MICU. SAP (n = 368) was often persistent: 45% (CI95 = 43-47%) after discharge from ED and 26% (CI95 = 22 30%) after MICU intervention. The prognostic factors of pain control success revealed by Chi squared test were: MICU (vs ED), treatment delay < or = 3 hours (vs > 3 hours), opioid use (vs non opioid use) and VAS pain level < or = 70 mm (vs > 70 mm). The last 3 factors were confirmed by multivariate analysis. Treatment delay, opioid use, and pain level were found to be determinants of efficient analgesia for SAP. CONCLUSION: Despite the high frequency of SAP in ED and MICU, pain control is not satisfying. Opioid use and early treatment are determinant in analgesia efficiency for SAP and should be therefore encouraged to improve pain relief in emergency medicine. PMID- 11759316 TI - [An experience with transthoracic echocardiography after heart surgery]. AB - OBJECTIVE: In order to determine if routine use of transthoracic echocardiography (TTE) shortly after heart surgery could have a role in postoperative management, we carried out TTE in postoperative patients operated on for CABG or valvular repair. PATIENTS AND METHODS: For a 3 months period, we prospectively enrolled 51 patients for TTE. We performed a TTE using a Hewlett Packard Sonos 1500 and a 2.5 MHz probe. Feasibility, left ventricular kinesis, valve function, intracardiac thrombi, and pericardial effusion were noted for each patient. Patients have been divided into 2 groups: patients with or, without haemodynamic disturbance (HD, mean arterial blood pressure < or = 80 mmHg). RESULTS: Nine TTE were impossible for bad acoustic images. Feasibility was about 82% (42 TTE/51 patients). Two ETT views were easily obtained: the apical 4-chambers (75%) and the subcostal (30%) views. TTE examination induced treatment change in 12 patients for hypovolaemia (ten patients), left ventricular dysfunction (one patient), and systolic anterior motion of mitral valve (one patient). In patients without HD (41 patients) only hypovolaemia was found (three patients) and TTE returned to normal with fluid challenge. In patients with HD (ten patients), one patient returned to the operating room for valvular replacement, one patient was treated with dobutamine for left ventricular dysfunction, seven patients with hypovolaemia recovered with fluid challenge. CONCLUSION: TTE can guide postoperative management of patients operated on for heart surgery especially in patients with haemodynamic disturbance. Because of its safety and easiness, TTE may be the first-line examination in these patients before any invasive evaluation. PMID- 11759317 TI - [Dural puncture in obstetric analgesia. Epidemiologic features and therapeutic management]. AB - OBJECTIVE: To assess the time of occurrence, circumstances and presenting symptoms of unintentional dural puncture (UDP), the location and intensity of postdural puncture headaches (PDPH), and the efficacy of their treatment by epidural blood-patch (EBP). STUDY DESIGN: Cohort study. PATIENTS: Cases of UDP recorded over a 4-year period in an obstetric anaesthesia unit. METHODS: The following variables were studied: maternal age, weight and height, hour of occurrence and number of puncture attempts, existence of reflux of cerebrospinal fluid (CSF) through the needle, experience of the practitioners, subsequent modalities of obstetrical analgesia, frequency of occurrence, clinical characteristics and therapeutic management of PDPH. In case of EBP, the amount of blood and the efficacy of the procedure were also recorded. RESULTS: Twenty-one patients presented with UDP (0.66%). No reflux of CSF was identified in nine cases. Most UDP occurred at the first or second attempt, usually when performed by a practitioner poorly trained in epidural analgesia in obstetrics. The risk of UDP was higher during night-time work (risk ratio: 3.0; 95% confidence interval: 1.1-8.0; p = 0.04). Subsequent analgesia was provided via the epidural route in 19 cases, subarachnoidal route in one, and intravenous route in one case. PDPH did not develop in two patients. Three patients were given prophylactic EPB, and 16 received curative EBP. A second EBP was required 24 h later in seven patients. One patient developed meralgia paresthetica following EBP. CONCLUSION: In parturients, UDP usually results in PDPH. A rapid and effective treatment is required, mainly EBP. Another EBP is eventually necessary in some patients. PMID- 11759318 TI - [Automatic analysis of electroencephalogram: what is its value in the year 2000 for monitoring anesthesia depth?]. AB - Spontaneous EEG has been proposed for monitoring depth of anaesthesia and adjusting anesthetic drugs doses. This review describes the main features of spontaneous EEG, the principles of EEG signal analysis used in anaesthesia, and the EEG effects of the different anesthetic drugs in adults and children. Then, the correlations between EEG parameters changes and clinical signs of anesthesia (loss of consciousness and memory, lack of movement and haemodynamic stability despite noxious stimulations) are analyzed. The best signal analysis technique available today for routine use seems to be bispectral analysis, which returns, in the available monitors, a single number called bispectral index or BIS. Based upon the recent literature, clinical uses, performances and limits of use of BIS are described and discussed. PMID- 11759319 TI - [A case of hepatic pseudoaneurysm treated with percutaneous embolization in a child with multiple trauma]. AB - Hepatic artery pseudoaneurysms are rare complications of blunt abdominal trauma in children. Diagnosis is frequently delayed and made by splanchnic angiography. Most of the indications for surgical treatment have disappeared after the development of selective catheterization and embolization. We report a case in an 8-year-old pedestrian who was struck by a car and suffered a multiple trauma with a severe blunt abdominal trauma. A severe collapse upon admission commanded immediate laparotomy that depicted a liver fracture with associated jejunal and pancreatic lesions. Recovery was progressive until the 15th postoperative day where an abrupt haemobilia occurred. A CT-scan exploration was performed and revealed a vascular mass lesion in the left lobe of the liver. The performance of a selective angiography confirmed the diagnosis of left artery pseudoaneurysm, but because of technical difficulties, no embolization could be performed by this way. A direct percutaneous puncture and embolization of the aneurysm allowed a complete exclusion of the lesion. Eventually, recovery was complete. This percutaneous technique could be a valuable alternative to classical embolization and could avoid surgical treatment that still carries a high morbidity. PMID- 11759320 TI - [Obstetric analgesia in patients with Klippel-Trenaunay syndrome]. AB - We report three cases of delivery in two parturients with a Klippel-Trenaunay syndrome. These patients have a rare hereditary disorder that results in three main features: haemangiomas, varicose veins, bone and soft tissue hypertrophy. In the absence of angiographic magnetic resonance imaging of the spinal cord and of perispinal tissues, arteriovenous malformations of the central nervous system could not been ruled out. Intravenous sufentanil and pudendal block were used for labour analgesia and vaginal delivery respectively; general anaesthesia was used for uterine revision and for caesarean section. PMID- 11759321 TI - [Community-acquired Acinetobacter baumannii pneumonia]. AB - We report two cases of community-acquired Acinetobacter baumannii pneumonia. Although most infections occur in hospitalized patients, a few cases of community acquired pneumonia have been described. This disease occurs predominantly in men, and is often associated with underlying conditions such as cigarette smoking, alcohol abuse, diabetes mellitus, and chronic pulmonary diseases. Community acquired Acinetobacter baumannii pneumonia cases are generally reported from tropical areas, especially during wet season. Microbiological identification in blood or sputum can be difficult because of frequent misinterpretation and possible confusion with Staphylococcus or Haemophilus infuenzae or neisseriae. Early antibiotherapy is required because of the fulminant clinical course, with approximatively 50% fatality rate. PMID- 11759322 TI - [Extracorporeal circulation with danaparoid sodium for valve replacement in thrombocytopenia induced by type II heparin]. AB - A type II heparin-induced thrombocytopenia (HIT) was diagnosed in a 64-year-old woman at day 20 of intravenous unfractionated heparin (UFH) therapy, given after myocardial infarction treated by angioplasty and intracoronary stent. The infarction was complicated by a mitral insufficiency that led to a mitral valve replacement. Cardiopulmonary bypass was successfully performed with sodium danaparoid (Orgaran), as an alternative to UFH, without thrombotic or haemorrhagic complications and the follow-up was uneventful. PMID- 11759323 TI - [Thigh cellulitis: atypical presentation of intra-abdominal infection]. AB - The initial clinical presentation of intraabdominal disease can be an extraabdominal location. We report three cases of patients admitted to our intensive care unit because of a severe soft tissue infection of the lower extremity. Systematic research of the primitive source by using computed tomography (CT) scan allows us to find perforation of the gastrointestinal tract. Despite an unusual presentation, a high index of suspicion for lower intestine perforation must always be considered in face of a patient presenting with a spontaneous thigh cellulitis. Immediate radical debridement, appropriate antibiotics, and intensive care support are critical to control these life threatening infections. PMID- 11759324 TI - [Rational choice, prediction, and medical decision. Contribution of severity scores]. AB - The aim of this study was to determine what type of representation the medical doctor adopted concerning the uncertainty about the future in critically ill patients in the context of preoperative evaluation and intensive care medicine and to explore through the representation of the patient health status the different possibilities of choice he was able to make. The role played by the severity classification systems in the process of medical decision-making under probabilistic uncertainty was assessed according to the theories of rational behaviour. In this context, a medical rationality needed to be discovered, going beyond the instrumental status of the objective and/or subjective constructions of rational choice theories and reaching a dimension where means and expected ends could be included. PMID- 11759325 TI - [Audit of the management of postoperative pain in children]. PMID- 11759326 TI - [Non-invasive ventilation can allow the transportation of and tomodensitometry tests in certain patients with acute respiratory failure]. PMID- 11759327 TI - [Peridural injection of glass pieces: a theoretical or a real risk?]. PMID- 11759328 TI - [Preanesthesia delocalized consultations and preanesthesia consultations for repeated and frequent anesthesia]. PMID- 11759329 TI - [Survey on addiction in the anesthesia setting]. PMID- 11759330 TI - [Preoperative prevention of hypothermia]. PMID- 11759331 TI - [Does PCA improve postoperative analgesia?]. PMID- 11759332 TI - Measuring and monitoring quality of life in children and youth: a brief commentary. PMID- 11759333 TI - [Health status of youth--an educational aspect in public health research]. PMID- 11759334 TI - Epidemiology of childhood arthritis in Switzerland. PMID- 11759335 TI - Changing images of John Snow in the history of epidemiology. AB - Ever since the end of the 19th century, the story of John Snow and his investigations into the contagiousness of cholera has fascinated epidemiologists. Several different lessons have been extracted from the interpretation and reinterpretation of Snow's work--according to prevailing insights. The story of John Snow continues to evolve, even into the 21st century. PMID- 11759336 TI - Quality of life in children and adolescents: a European public health perspective. AB - OBJECTIVES: The measurement of health-related quality of life (HRQOL) is increasingly important as a means of monitoring population health status over time, of detecting sub-groups within the general population with poor HRQOL, and of assessing the impact of public health interventions within a given population. At present, no standardised instrument exists which can be applied with equal relevance in pediatric populations in different European populations. The collaborative European KIDSCREEN project aims to develop a standardised screening instrument for children's quality of life which will be used in representative national and European health surveys. Participants of the project are centres from Austria, France, Germany, Netherlands, Spain, Switzerland, and United Kingdom. By including the instrument in health services research and health reporting, it also aims at identifying children at risk in terms of their subjective health, thereby allowing the possibility of early intervention. METHODS: Instrument development will be based on constructing a psychometrically sound HRQOL instrument taking into account the existing state of the art. Development will centre on literature searches, expert consultation (Delphi Methods) and focus groups with children and adolescents (8-17 years). According to international guidelines, items will be translated into the languages of the seven participating countries for a pilot test with 2,100 children and their parents in Europe. The final instrument will be used in representative mail and telephone surveys of HRQOL in 1,800 children and their parents per country (total n = 25,200) and normative data will be produced. The potential for implementing the measurement tool in health services and health reporting will also be evaluated in several different research and public health settings. The final analysis will involve national and cross cultural-analysis of the instrument. RESULTS: The international, collaborative nature of the KIDSCREEN project means it is likely to provide many challenges in terms of producing an instrument which is conceptually and linguistically appropriate for use in many different countries, but it will also provide the opportunity to develop, test and implement the first truly cross-national HRQOL instrument developed for use in children and adolescents. This will help to contribute to a better understanding of perceived health in children and adolescents and to identify populations at risk. PMID- 11759337 TI - Temporal and spatial pattern of infant mortality in Germany after unification. AB - OBJECTIVES: After unification in 1990 the two parts of Germany underwent a complex process that has led to convergence of infant mortality. The pattern of change did, however, differ in east and west. This study investigates whether these differences conceal a complex pattern of heterogeneity at the regional level. METHODS: Examination of routine data on infant, neonatal and postneonatal mortality. Time trends in the 16 federal states of Germany (Lander) from 1991 to 1997 were studied using a log-linear model. RESULTS: In 1991, infant mortality was higher in almost all eastern Lander than in the west. By 1997, this east-west gap had disappeared. Over this period, infant mortality fell in all Lander but one. The decline was steepest in the east, ranging from 31% to 52%. Improvements were largely due to steep declines in both neonatal and postneonatal mortality. CONCLUSIONS: This study shows that, at the time of unification, there was an almost complete demarcation between east and west, a pattern that disappeared by 1997. There is, however, still a substantial regional variation in infant mortality that is largely determined by postneonatal mortality. PMID- 11759338 TI - [Childhood and myocardial infarct: socioeconomic and psychosocial influences in childhood on risk of myocardial infarct]. AB - OBJECTIVES: Compared to the established risk factors of myocardial infarction (MI) little is known about the impact of socio-economic and psycho-social risk factors during childhood. METHODS: Based on the WHO MONICA infarction register of the Erfurt reporting unit (1990-1993), 129 male cases and 129 controls (patients of accident surgery without psychiatric or heart disease, matched by age groups) were surveyed by a qualitative interview. The MI risk was analysed for general conditions of childhood, stressful life events, serious changes during childhood, and dissatisfaction with childhood using univariate and multiple logistic regression models. RESULTS: A significantly higher risk was found for worse (OR = 5.1; CI: 1.5-18.1) and mediocre (OR = 2.0; CI: 1.0-4.1) housing conditions as well as migration (OR = 3.0; CI: 1.1-8.3) during childhood. A significantly increased risk of MI is also found for individuals who reported three or more stressful life events (OR = 3.2; CI: 1.1-9.4) during childhood. In comparison, smoking habits (current or ex-smokers)--an established impact factor on MI--was associated with a slightly lower risk (OR = 2.6; CI: 1.3-5.3). CONCLUSIONS: Both socio-economic determinants and psycho-social factors of childhood carry significant risk for myocardial infarction in later life. Our data support the hypothesis that risk factors of MI are affected and/or triggered by socio economic living conditions during childhood in general, and by stressful life events during childhood in particular. PMID- 11759339 TI - [Correlation between educational status, chronic diseases and cardiovascular risk factors in young adults 18-29 years of age: results of a 1998 comprehensive German health survey]. AB - OBJECTIVES: The aim of the study is to investigate the association between educational attainment and the prevalence of chronic diseases and cardiovascular risk factors for the German population aged 18-29 years. METHODS: The data source is the Federal Health Survey 1998 (BGS98), which is representative for Germany. The response rate for the survey is 61.4%. Included in the analysis are 616 females and 637 males. Indicator for educational atteinment is the highest achieved school degree ("Abitur" n = 375, "mittlere Reife" n = 566, "Hauptschule" n = 312). RESULTS: For eight of the 43 items for self-reported diseases in the BGS98-questionnaire persons in the age group 18-29 yielded a higher prevalence than older adults. For altogether 11 diseases, which showed a prevalence greater than 3% in the age group 18-29 years, only minor associations with educational attainment were observed. Statistically significantly increased prevalences are observed for allergic disorders in persons with higher education and for long term headache in persons with lower education. Regarding smoking, obesity and lack of sports activities remarkably and statistically significant education related differences are observed. The percentage of persons showing simultaneously two or three of these risk factors was 33% for study subjects with "Hauptschulabschluss" compared to only 8% for study subjects with "Abitur". CONCLUSIONS: Educational attainment is still a strong predictor for health behaviour. This finding should be considered in future health promotion compaigns. PMID- 11759340 TI - Are there age-dependent effects of diet on prostate cancer risk? AB - OBJECTIVES: To examine whether there are age-dependent effects of diet on prostate cancer risk. METHODS: We have postulated that nutritional factors that may affect the risk of initiation would be more likely to be identified among younger patients, whereas those that may affect the risk of progression would be more clearly identifiable among older patients. Study subjects were 320 patients with prostate cancer and 246 controls with no systematic disease, hospitalised in six major hospitals in Athens, Greece. Logistic regression models were fitted separately for men under 70 years and 70 years or older. RESULTS: Polyunsaturated lipids substantially increased the risk among younger subjects, but played little role among older ones (p for interaction 0.21). Cooked tomatoes had a strong protective effect among older persons, but not among younger subjects (p for interaction 0.009). Last, vitamin E was strongly inversely related to prostate cancer risk among younger subjects, but not among older subjects (p for interaction 0.15). CONCLUSIONS: Even a simple straight forward interpretation of the data, i.e., that older cases of prostate cancer have a different dietary risk profile than younger ones, has potentially useful implications. PMID- 11759341 TI - The impact of hearing disability on well-being and health. AB - OBJECTIVES: The aim of the paper is to assess the significance of hearing disability as a public health problem through its association with multiple negative health outcomes: subjective health perception, mental health and social well-being. METHODS: The data come from the participants of the 1997 national health survey in Belgium, who were 15 years and older (n = 8,560). The presence and severity of the hearing disability was estimated through self-reporting. The association of hearing disability with the studied health outcomes was assessed using logistic regression while controlling for confounding factors such as age, sex, co-morbidity and socio-economic status. RESULTS: The prevalence of hearing disability is 7% in the population 15 years and older. The prevalence of subjective ill health (Odds Ratio (OR): 1.32), mental ill health (OR: 1.51), and a low appreciation of the social contacts (OR: 1.73) was higher in subjects with hearing disability. No association was found between hearing disability and the frequency of social contacts or with the functional content of the social contacts. CONCLUSIONS: Given the health and social consequences of hearing disability, increased public health attention, including both strategies for prevention, for identification and treatment, is warranted. PMID- 11759342 TI - [Deglutition disorders in the elderly. Epidemiological aspects]. AB - THE PREVALENCE: The exact prevalence of deglutition disorders in the elderly is not known. It appears frequent in very old patients and in those suffering from polypathological symptoms, affecting 50% of the populations in long-term care units. THE EFFECTS OF AGING: Physiological aging alters various parameters of swallowing, however it seems that these modifications related to age have little effect on healthy subjects. However, they may increase vulnerability in those presenting with intercurrent pathologies. CONCOMITANT DISORDERS: Other than the decrease in efficient mastication and the existence of xerostomia, frequently observed contributing factors, many diseases may be responsible for dysphagia in the elderly. Neurological disorders, particularly cerebral vascular diseases, central nervous system degenerative disorders and neuro-motor diseases predominate. In the aging, muscular disorders and after effects of various diseases can set-in. Modifications in oropharyngeal anatomy generally results from cancerous lesions of the aero-digestive junction, but also, occasionally from extrinsic compression that does not necessarily reflect a neoplastic etiology. Zenker's diverticulitis represents a cause of dysphagia specific to the elderly. Problems in swallowing of iatrogenic origin are also frequent, following cervical radiotherapy or after oropharyngeal surgery, during tracheal intubation or when using feeding tubes and also during various medical treatments. UNDERRATED CONSEQUENCES: Dysphagia leads to multiple morbid after effects, primarily alteration in quality of life, dehydration, undernutrition, asphyxia and congestion and recurrent infections of the respiratory tract. The responsibility of deglutition disorders in the occurrence of these complications is difficult to assess in weak elderly subjects because of the frequent concomitance with multiple deficiencies and incapacities. PMID- 11759343 TI - [Deglutition disorders in the elderly. Evaluation methods]. AB - FROM DISCOVERY TO CLINICAL DIAGNOSIS: Dysphagia is easy to diagnose in its acute stage and when complicating a known neurological disease. However diagnosis may be greatly delayed when expressed by respiratory or nutritional symptoms, or when the patient presents cognitive disorders, as is frequent in the elderly. In such instances, simple tests such as the water test are clearly indicated. However, although they are reliable for diagnosing dysphagia, they are not precise in diagnosis of inhalation. Clinical examination is essential for diagnosing the etiology of the disorder. In the absence of clinical orientation, a nasofibroscopy is mandatory and digestive endoscopy debatable. SPECIALIZED EXAMINATIONS: The first-line supplementary examination is a videoradiography. It consists in the patient swallowing a liquid or solid barium sulfate bolus. This detects any anatomical or functional abnormalities. It is the examination of choice for the diagnosis of inhalation and its mechanism. Videoendoscopy is complementary to videoradiography. It can be conducted in first intention in patients who cannot be transported to the radiology unit. It provides precise information on glottal closing and pharyngeal contraction. IMPACT ON MANAGEMENT: In a restricted number of patients, the precise knowledge of the mechanism of dysphagia can help to orientate specific treatment. In others, such examinations will orient re-education, postural adaptation and the modification of food texture. In many patients, precise diagnosis of the mechanism at the origin of dysphagia has no impact on the management of dysphagia. PMID- 11759344 TI - [Deglutition disorders in the elderly. Management]. AB - GENERAL PRINCIPLES: The management of dysphagia requires multi-disciplinary interventions, implying various procedures, the choice of which depends on the results of the global prior assessment of the patient. General measures for oral hygiene, dental care and the organization of conditions in which meals are taken are essential, particularly for dependent patients. A change in food texture or in viscosity of liquids is a strategy commonly used. However, such changes must depend on objective bases and not unnecessarily penalize patients or expose them to further risks of complications. COMPENSATION AND RE-EDUCATION TECHNIQUES: Various strategies can help to counteract deficient deglutition mechanisms. Among these, adopting a particular position while swallowing is helpful in many dysphagic patients, but may be limited by severe cervical stiffness. The swallow reflex can be enhanced by sensorial stimulation techniques, although they are only effective short-term. Execution of voluntary maneuvers improves efficacy and safety when swallowing, but learning these maneuvers can be difficult or even impossible, even when accepted by the patients and compliance is inconsistent. Re education techniques are intended to lastingly improve swallowing, but it is difficult to obtain the active participation of many elderly patients. Furthermore, these commonly used techniques lack seriousness and require validation. MISCELLANEOUS PROCEDURES: The efficacy of pharmacological intervention is not clear, other than in certain particular etiological contexts and, as with procedures enhancing the stimulating properties of food and liquids, will obviously be developed in the future. Surgery, or related techniques, provides help in certain specific conditions, notably when an anatomical disorder is responsible for the disorder. Gastrostomy is still controversial, not only with regard to its optimal practical use and its capacity to decrease respiratory infection risks and improve nutritional prognosis, but also with regard to its impact on patients' survival and quality of life. PMID- 11759345 TI - Risk-taking, intrasexual competition, and homicide. PMID- 11759346 TI - The adaptive toolbox: toward a darwinian rationality. PMID- 11759347 TI - Cognitive strategies and the representation of social relations by monkeys. PMID- 11759348 TI - Motivation and melancholy: a darwinian perspective. PMID- 11759349 TI - Adaptive design, selective history, and women's sexual motivations. AB - I have discussed an ongoing program of research designed to examine the nature of specific sexual selection pressures that have played a role in the evolution of human mating. I have suggested that the evidence tentatively be interpreted as consistent with the existence of female preferences for traits that indicate good genes. Nonetheless, more research is needed before definitive conclusions can be reached. At the outset, I discussed several points about the application of adaptationism to an understanding of human behavior. First, special-design arguments are often critical to evolutionary explanations. Special design is not only evidence that natural selection has been at work, it can also reveal the nature of selection pressures that have shaped the organism. Second, special design often cannot be readily "read off" the observed phenotype. A convincing special-design argument may require a coordinated, coherent explanation (a nomological network; Cronbach & Meehl, 1955) of multiple and varied observations. Third, observations that are "strange coincidences" if one's explanation is not correct, but expected if one's explanation is correct, are particularly informative pieces of evidence. The research on sexual selection illustrates these points. We have attempted to provide evidence for special design in females for preferring men who demonstrate developmental precision for the benefit of obtaining good genes. We can point to no one piece of evidence that directly demonstrates this special design. The explanation that women possess special design for preferring men who possess good genes in certain mating contexts (such as extra-pair sex), however, does provide a coherent account of a wide range of findings. At least one of these findings--that women prefer the scent of symmetrical men only when the probability of conception is high--was expected by this explanation, but has no obvious alternate explanation and hence appears to be a strange, peculiar coincidence if this explanation is wrong. By no means do we have a full and complete story here. The nomological network can and should be expanded in a number of ways and, thereby, the argument for special design tightened. Whether or not the special-design argument ultimately holds up to further scrutiny, however, I would like to think that our efforts to establish it have importantly contributed to an understanding of human mating. PMID- 11759350 TI - Pheromones and vasanas: the functions of social chemosignals. PMID- 11759351 TI - Introduction: fear and loathing of evolutionary psychology in the social sciences. PMID- 11759352 TI - Rethinking the critical care environment: luxury or necessity? AB - Rethinking the critical care environment, an implicit call to change, can catalyze a return to nursing's intellectual roots. Healing environments, as envisioned by Florence Nightingale, involve system-level changes that require effective negotiations on behalf of our patients and ourselves. The nurse-patient relationship is central to the patient's environment and requires a comprehensive understanding of healing. Only nurses can articulate the changes necessary to ensure quality nursing care, and our collective "silencing" must be confronted if it is to change. Nurses' tendency to avoid, accommodate, or compromise when faced with conflict also must change. Giving voice to nursing concerns itself becomes a call to excellence, and those unwilling to change are best excluded. Although all of this is difficult, it is no more difficult than the nonhealing environments where we now work, and at least gives promise of more positive outcomes. PMID- 11759353 TI - The role of the clinical nurse specialist in creating a healthy work environment. AB - The clinical nurse specialist (CNS) contributes to a healthy work environment through partnerships with the nursing staff, nurse manager, physicians, and other colleagues across the health system. Examples of these partnerships are described in this article, highlighting how the work of the CNS influences the care that patients and families receive, shapes the practice environment, and fosters collegial and respectful relationships among caregivers. The CNS is a pivotal figure in creating an environment where nurses can provide the care that is needed and feel valued for their work. Partnership with a variety of clinicians enables the CNS to influence critical care nursing practice, the intensive care unit team, and the environment in which care is provided. PMID- 11759354 TI - The nurse manager's role in creating a healthy work environment. AB - The role of nurse manager of an acute or critical care unit is one of the most difficult roles in healthcare today. This individual must juggle patient care issues, staff concerns, medical staff relationships, supply inadequacies, and organizational initiatives--and then balance all of this with a personal life. The only way in which any of this is remotely possible is if the patient care unit provides a supportive environment for patients, families, and staff. The nurse manager is a pivotal person in this effort: research repeatedly shows that people don't leave their jobs, they leave their managers. This article describes how the nurse manager of an acute neurosciences unit worked with her staff to define, create, and maintain a work environment in which patient care improved, people enjoyed working, and retention of staff increased. PMID- 11759355 TI - Medical directors as partners in creating healthy work environments. AB - Relationships between nurses and physicians in the intensive care unit can range from collegial and supportive to dysfunctional and abusive. When there is trust, open communication, respect, and a sense of camaraderie, the work is still challenging but gets done: priorities are met and people feel good about what they are doing. When these key elements are missing, satisfaction on the part of staff and patients decreases and turnover and costs increase. More importantly, research findings suggest that improving collaboration and teamwork are more than "feel-good" exercises: patient outcomes of care can be jeopardized when nurses, physicians, and other members of the critical care team are not communicating or collaborating. The nurse manager and medical director of the unit, as leaders of this team, are responsible for ensuring not only that quality care is delivered to patients, but also that the environment is supportive to caregivers. Purposefully establishing a collaborative partnership and then modeling these behaviors to the rest of the team, and holding them accountable, are key steps in creating an environment that is healing to patients, families, and caregivers. PMID- 11759356 TI - Instituting a disruptive conduct policy for medical staff. AB - A healthy work environment is one that promotes interaction and communication among all professionals, a positive and strong working relationship between the nurse manager and physician director, and activities such as joint patient care rounds, shared clinical protocols, and joint teaching of physicians and nurses. There are situations when a physician's unacceptable conduct leads to a disruptive environment for patients, staff, and fellow physicians. This article describes the steps taken in one institution to establish structures and systems to communicate behaviors that are unacceptable and a policy to be followed should disruptive behavior be encountered. Having systems and structures in place assists in promoting a healthy work environment. PMID- 11759357 TI - Creating a collaborative environment to care for complex patients and families. AB - Today's critical care environment is increasingly complex due to technological advancements, greater intensity of interventions, and a myriad of healthcare providers. Critically ill patients and their families can feel overwhelmed with the stress of the environment in addition to the acute illness. This stress affects the patients' and families' ability to function, cope, and understand complex information. For some families, this experience precipitates distrustful relationships with care providers. The resulting impact on quality of care, staff morale, length of stay, and cost is high. The purpose of this article is to describe issues encountered by one medical center in caring for complex patients and families. A representative case outlines the types of issues the staff in the adult intensive care units faced. Use of a comprehensive problem-solving model to address concerns resulted in structured approaches to guide healthcare providers in caring for complex patients and families. The goal of these approaches was to support all parties involved in the care of complex patients, improve communication, and avoid crises that resulted from distrustful relationships and lack of skill in resolving conflict. PMID- 11759358 TI - Supportive work environments for nursing faculty. AB - Whereas most of the concern about increasingly stressful work environments has focused on acute-care hospitals, the academic healthcare environment is not immune. Faculty, staff, and students in schools of nursing report similar stressors. Pressures from managed care, personnel shortages, and unceasing change are affecting the academic environment and yielding stressful, dysfunctional, and occasionally abusive settings here as well. This article describes the role of the dean in creating a healthy work environment in which students can learn and faculty can teach and do research. Future nurses are introduced to critical care as students, and the learning environment significantly influences them. Graduate students in critical care can experience encounters that range from supportive to obstructive. Knowing what is reasonable to expect from a dean and faculty should help students in critical care sort out the issues if they are experiencing an abusive situation, and what options they might pursue. PMID- 11759359 TI - Magnet nursing services recognition: transforming the critical care environment. AB - History repeats itself despite the best intentions of those in the nursing profession. Once again there is an emerging shortage of nurses, and critical care units are particularly affected. The work environment in critical care and medical/surgical units is demanding and stressful, but little effort has been made to mitigate the working conditions that cause nurses to leave. It is possible to apply lessons from magnet hospital research spanning the past 18 years to alter the pattern of repeated nursing shortages. The process of receiving the magnet nursing services designation has transformed the work environment for all nurses at the University of California Davis Medical Center. This broadly focused article describes the transformation process and the culture of an institution that values and consequently retains the best nurses to provide outstanding patient care despite the nursing shortage. PMID- 11759360 TI - Success indicators and barriers to acute nurse practitioner role implementation in four Ontario hospitals. AB - Changes in healthcare environmental factors resulted in the introduction of the acute care nurse practitioner (ACNP) role in Ontario. The purpose of the study was to identify success indicators, barriers, and recommendations for role implementation to assist healthcare providers to develop strategies for integrating ACNPs into teams. Acute care nurse practitioners (n = 14), physicians (n = 14), administrators (n = 12), and staff nurses (n = 48) from four tertiary care hospitals completed a researcher-developed, self-administered questionnaire with fixed and open-ended questions. Specialty practice areas (cardiac/critical care, geriatrics, and nephrology) were matched within the four sites. Acute care nurse practitioners (n = 14), physicians (n = 12), administrators (n = 8), and staff nurses (n = 34) responded. The major indicator by all groups for successful role implementation was level of preparation. Barriers included lack of mentorship and knowledge of the role, and perceived lack of support from administration and physicians. Themes reflecting impact on patient care were improved communication and attention to patient care issues. Respondents accepted the role, concluding that enhanced continuity of care was a result. Role clarity before and during implementation would assist team members in understanding the purpose and value of the role, thus easing the integration of the ACNP into the healthcare team. PMID- 11759361 TI - Comprehensive trauma patient care by nonphysician providers. AB - Nonphysician providers are being increasingly used to care for trauma patients. As these complex patients recover, they require meticulous medical management and time-consuming psychosocial care. A retrospective evaluation of a unique patient care service staffed by nonphysician providers is presented. The Intermediate Care Service is designed to facilitate the management and long-term placement of trauma patients who no longer require intensive care while recovering from their injuries. The new diagnoses, physician order changes, and disposition of 93 patients cared for during a 6-month period are described. Most patients were admitted with neurologic injury. The most common new diagnosis was constipation; the most frequent new orders related to medications, including bowel management, and rehabilitation consultations. All patients were discharged from the hospital. The Intermediate Care Service represents a unique and valuable model for the collaborative management of complex trauma patients. PMID- 11759362 TI - Longitudinal survey of acute care nurse practitioner practice: year 2. AB - The acute care nurse practitioner (ACNP) is a unique advanced practice nursing role that has expanded since the first national certification examination became available in 1995. This article reports on the results of year 2 of an annual survey of ACNPs as part of a 5-year longitudinal study exploring ACNP role development. Responses from 545 ACNPs 2 years after national certification reveal continued development and challenges in practice. Role components continue to highlight the comprehensive care model of ACNP practice in terms of coordination of patient care, interactions with family members, consultation, and discharge planning. Important issues identified by participants including the need for clinical experience, the importance of negotiation, and networking also are discussed. PMID- 11759363 TI - Mentoring: a call to professional responsibility. PMID- 11759364 TI - Mode of delivery following labor epidural analgesia: influence of ropivacaine and bupivacaine. AB - Epidural analgesia is a popular and effective method for pain relief during labor. Bupivacaine is a commonly used local anesthetic for labor epidural analgesia. Ropivacaine is an amino acid local anesthetic that is structurally related to bupivacaine with a similar potency and duration, but ropivacaine has less cardiac toxicity than bupivacaine and produces less motor blockade. These properties make ropivacaine a desirable local anesthetic agent for obstetrical analgesia. The purpose of the present study was to compare the cesarean section and instrumental delivery rates for patients receiving labor epidural analgesia using bupivacaine and ropivacaine. The medical records of 500 consecutive patients receiving bupivacaine for labor epidural analgesia were reviewed. After a 3-month familiarization period for ropivacaine, the records of 500 consecutive patients receiving ropivacaine for labor epidural analgesia similarly were reviewed. The groups did not differ demographically. The instrumental delivery rate was 14.2% for the bupivacaine group and 9.8% for the ropivacaine group. The cesarean section rate was 14% for the bupivacaine group and 10.2% for the ropivacaine group. At our facility, the use of ropivacaine decreased both cesarean section and instrumental delivery rates when compared with bupivacaine in the population studied. PMID- 11759365 TI - Learning from a nurse anesthetist perspective: a qualitative study. AB - This study explored the learning and problem-solving experiences of Certified Registered Nurse Anesthetists (CRNAs) using a qualitative case study design. Through interviewing and observation techniques, 5 expert CRNAs provided information on learning and problem solving in daily clinical practice. Data were analyzed using the Tesch 8-step model. Three themes emerged from the data. In their learning, expert CRNAs first desire to know the pharmacological, physiological, or pathophysiological ("basic") principles needed to understand clinical situations. Once they are comfortable with their grasp of the basic principles, CRNAs will then "try out" the new agent or technique in their clinical practice. As experiences accumulate, CRNAs create complex practice structures and demonstrate increased levels of confidence, comfort, and expertise in practice. In understanding how expert nurse anesthetists learn and develop, perhaps educators and students will be more able to identify and design learning activities that prepare students for competent and successful anesthesia practice. PMID- 11759366 TI - New advances in the treatment of sickle cell disease: focus on perioperative significance. AB - Sickle cell diseases comprise a group of inherited disorders that alter hemoglobin, ultimately causing hemolytic anemia and reoccurring instances of vascular occlusion that produce acute and chronic pain. Many patients with sickle cell disease require surgery for conditions associated with their disease. Painful vaso-occlusive episodes, which can be debilitating and require long hospital stays, are often precipitated by the stress of surgery. Poorly controlled postoperative pain also can worsen an impending painful crisis. Traditional therapy for patients with sickle cell disease undergoing surgery has included preoperative transfusion and postoperative opioid therapy. Recent studies have demonstrated that aggressive preoperative transfusion therapy is not beneficial over a more conservative approach. Postoperative pain control trends include nonsteroidal anti-inflammatory drugs such as ketorolac and opioid agonist antagonist agents such as nalbuphine, as well as epidural analgesia to minimize respiratory depression. New preventive therapy for vaso-occlusive crisis includes hydroxyurea, a chemotherapeutic agent that stimulates the production of fetal hemoglobin. Inhaled nitric oxide is being used in clinical trials with success in slowing the sickling process and unsickling cells. Phase III clinical trials are in progress for 2 drugs that decrease sickling: poloxamer 188 and fructose 1-6 diphosphate. These new therapies should help improve the anesthetic course of the patient with sickle cell disease, reduce postoperative complications, and shorten hospital stays. PMID- 11759367 TI - Modified rapid-sequence induction of anesthesia: a survey of current clinical practice. AB - The purpose of this study was to identify the use of rapid-sequence induction (RSI) and its hybrids. For the study, 67 Certified Registered Nurse Anesthetists at 1 hospital completed a survey describing their experience using a modified technique for patients with a moderately increased risk of regurgitation and aspiration. Patient selection criteria and the use of aspiration prophylaxis, preoxygenation, cricoid pressure, and positive-pressure ventilation were evaluated. In contrast with routine induction and standard RSI techniques, the modified RSI technique consisted of aspiration prophylaxis, preoxygenation, application of cricoid pressure, and positive-pressure ventilation. The survey revealed that a modification of standard RSI is used commonly in clinical practice. These modified RSI techniques are not standardized, as variation was noted in the delivery of positive pressure ventilation. Further study is necessary to identify widespread use of modified RSI techniques and to clarify the risks and benefits of modified RSI. PMID- 11759368 TI - Data-driven practice improvement: the AANA Foundation closed malpractice claims study. AB - Research in anesthesia risk management has focused primarily on adverse patient outcomes. Most risk management studies have evaluated the practices of the physician anesthesiologist, while minimal research has been conducted to examine anesthesia care provided by Certified Registered Nurse Anesthetists (CRNAs). For this reason, the American Association of Nurse Anesthetists Foundation supported an examination of closed malpractice claim files from St Paul Fire and Marine Insurance Company that involved insured CRNAs. A team of 8 CRNA researchers investigated 223 closed claim files that involved incidents from 1989 to 1997. The results indicated that preoperative physical status, patient age, surgical procedure, type of anesthetic, age of anesthesia provider, and the type of anesthesia providers, (e.g., CRNA alone vs CRNA and anesthesiologist working together) did not have a statistically significant relationship with adverse anesthetic outcomes. However, providing appropriate care, being vigilant, encountering a less severe adverse outcome, and not being able to prevent the outcome were associated with smaller monetary awards. The findings of this study support those of similar studies. PMID- 11759369 TI - Asthma: an anesthetic update. Part 3. AB - The effective management of the patient with asthma continues to represent a significant challenge in modern anesthesia practice. The prevalence of asthma is increasing worldwide and is the most common chronic disorder among children. Classification and treatment strategies continue to evolve as new therapies emerge. Fortunately, the incidence of bronchospastic episodes under anesthesia has declined in recent years with the development of improved anesthetic drugs and techniques. A thorough understanding of the pathogenesis of asthma will assist in developing anesthetic management plans that are patient specific and use the best treatment pathways currently available. PMID- 11759370 TI - [Hemoglobin level among infants in Akko sub-district]. AB - OBJECTIVES: To determine the prevalence of anemia among infants born in 1995 within the Akko sub-district and to investigate the association between anemia and socio-demographic variables. SUBJECTS AND METHODS: In 1995, 7920 children were born in the Akko sub-district. Recommendations for prophylactic doses of iron preparations were given to all the infants aged 4-12 months screened by the "Mother and Child" clinic's team. Procedures at the "Mother and Child" clinic require the clinic's nurses to perform a routine hemoglobin test for each child at the age of 12 months. Anemia was defined as a level of hemoglobin less than 11 g/dl. The chi-square test was used for statistical analyses. RESULTS: A hemoglobin test was performed on 5703 infants. The finding showed that 30.8% of these infants had a hemoglobin level below 11 g/dl, 24% had a hemoglobin level between 10.0-10.9 g/dl, 6%--between 9.0-9.9 g/dl and less then 1% of the infants had a level of hemoglobin below 9.0 g/dl. Statistical analysis was performed on the results obtained from 5535 infants of non-Jewish origin. An association was found between the rate of anemia and ethnicity (Arabs more than Druze, p = 0.02) and between the rate of anemia and the type of settlement (p = 0.001). Arab settlements of higher socio-economic level showed a lower rate of anemia than those of low socio-economic level. The highest rate of anemia was found within Bedouin settlements. The number of children in the family was significantly associated with anemia rates (p = 0.0005), showing dose response effect. There was inverse correlation between maternal education and anemia rate (p = 0.001). No association was found between birth weight and anemia rates. CONCLUSIONS: A high rate of anemia was found among non-Jewish infants in the Akko sub-district. This finding indicates the necessity for an intervention program to reduce this high rate of anemia and its associated damage in order to facilitate the optimal psychomotor development of the children. PMID- 11759371 TI - [Prevalence of fibromyalgia in type 2 diabetes mellitus]. AB - This study aimed to assess the prevalence of fibromyalgia and other pain characteristics among patients with type 2 diabetes mellitus. We assessed 137 patients with type 2 diabetes mellitus and a control group of 139 patients matched for age and sex that do not suffer from diabetes mellitus. We examined 9 of 18 typical tender points and 4 control points with a dolorimeter. There was no difference in the prevalence of fibromyalgia among men in both groups. However, diabetic men had more tender points than men in the control group and their threshold for pain at the corresponding tender points was significantly lower compared to that of the men in the control group. The diabetic men also reported more pain than patients in the control group. Diabetic women, on the other hand, had a significantly higher prevalence of fibromyalgia than women in the control group: 23.3% versus 10.6% respectively (p = 0.043). There was no significant difference in the number of tender points and the pain threshold in the two groups of women. Diabetic women reported more pain than the women in the control group. In both diabetic men and women the number of tender points and dolorimeter count directly correlated with the duration of diabetes. PMID- 11759372 TI - [Liver function test impairment induced by propafenone in a 73 year old woman]. AB - Propafenone hydrochloride is a drug used for treating arrhythmia. The drug is usually well tolerated, although there are cardiovascular as well as non cardiovascular side effects. The latter usually occur in the digestive tract and the neurological system. The rarest side effect is cholestasis. The literature cites five reported cases. This phenomenon is generally accompanied by clinical symptoms and upon discontinuation of the treatment with propafenone, the liver function tests return to the normal range. We review the literature dealing with liver damage resulting from treatment using propafenone. This is a case study of a 73-year old woman with three exposures of cholestasis connected to treatment with propafenone. The literature background and the case history were presented in order to heighten the physician's awareness of this rare phenomenon. PMID- 11759373 TI - [Severe accidental hypothermia in an elderly woman]. AB - Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia. Respiratory and metabolic, sometimes lactic, acidosis, lethargy and coma, hypercoagulopathy, hyperosmolar state, acute pancreatitis and renal and hepatic failure are frequent complications of hypothermia. Underlying predisposing causes of hypothermia are diabetic ketoacidosis, cerebrovascular disease, mental retardation, hypothyroidism, pituitary and adrenal insufficiency, malnutrition, acute alcoholism, liver damage, hypoglycemia, sepsis, hypothalamic dysfunction, sepsis and polypharmacy, and especially, the use of sedative and narcotic drugs. Our case demonstrates once again that CPR once begun should continue until the successful rewarming because "no one is dead until warm and dead". PMID- 11759374 TI - [Survival of a 300 gram infant]. AB - Despite progress in neonatal medicine and the development of new methods of treatment such as surfactant administration and new modalities of ventilation, mortality remains significant among newborn infants weighing less than 500 gram. Neurodevelopmental outcome of infants born before 26 weeks gestation is perceived as very poor. As the result of recent reports, there have been calls for limitation of medical care for these infants. We report of only 4 infants weighing less than 400 grams, who have survived. Two of these infants developed respiratory failure and required aggressive conventional mechanical ventilation. We report on the survival of an infant delivered before the completion of 26 weeks gestation period and weighing 300 grams. The infant was ventilated by high frequency oscillatory ventilation for respiratory distress syndrome. She is the second smallest infant reported in the medical literature. PMID- 11759375 TI - [Attention deficit disorder in the preschool years: its characteristics and course from infancy to toddlerhood]. AB - Diagnosis of Attention Deficit Disorder with/without hyperactivity in school-age children is based on the presence of the three main symptoms: lack of attention, impulsivity and hyperactivity. In infants and toddlers, these symptoms may very well be contingent to their development stage, but may also signify early signs of attention deficit disorder. Diagnosis in the age group of 2-5 years is very challenging, because reliable criteria are still lacking. The cutpoint between normal developmentally-based lack of attention and impulsivity and "true" attention deficit, is often not clear enough. Also, the very young child's condition often reflects the quality of the early parent-child relationship. Diagnostic criteria, differential diagnoses and treatment relevant to this age group, are presented. An 18 month old boy with signs of irritability, sleep problems, and poor attention span, shows the course of these symptoms, from infancy to toddlerhood under treatment, with modalities that changed over time. We suggest adopting an integrative standpoint of the young child and his/her family in the diagnostic as well as the therapeutic process, while keeping in mind the dynamic and development-dependent nature of the clinical presentation. PMID- 11759376 TI - [Neurosurgical aspects in achondroplasia: evaluation and treatment]. AB - Achondroplasia is the most common genetic disorder associated with bone dysplasia. The mode of inheritance is autosomal dominance, while most cases appear to represent a new mutation. Achondroplastic patients suffer from dwarfism, and from typical features of the head and limbs (rhizomelia, macrocephaly, frontal bossing and kyphosis). Half of the patients show various neurological complications. The most serious complication of achondroplasia is respiratory impairment, apnea and sudden infant death, resulting from compression of the medulla oblongata. This study describes the neurosurgical sequels in 10 achondroplastic patients, who underwent 12 surgical procedures. The average age was 14 years (ages ranged from 3 months to 40 years). The patients suffered from back pain, muscle weakness, incontinence, hypotonia, psychomotor delay, apnea and respiratory arrest. Four patients were diagnosed as suffering from obstructive sleep apnea. Craniocervical MRI showed: narrowing of the foramen magnum, fusion of C1, spinal stenosis, and severe cervicomedullary or spinal cord compression. In 5 patients the MRI also showed ventriculomegaly of the lateral and third ventricles. Seven patients underwent foramen magnum decompression and C1 laminectomy. Three patients with severe spinal cord compression underwent laminectomy of the involved spines (T12-L5). Two of the patients required more then one operation due to the recurrence of their neurological symptoms. There was no need for duraplasty or shunt procedures. The average hospital stay was 6 days. Eight patients showed improvement or resolution of symptoms, with an average follow-up period of 13.5 months after the last operation (ranged 6-24 months). We conclude that early neurological and MRI evaluations are required in achondroplasia patients, in order to prevent the high morbidity and mortality during infancy and childhood. In adults, MRI evaluation is needed if the patient has neurological symptoms. Early identification and immediate cervicomedulary decompression procedure can prevent the serious complications occurring in achondroplasia, including respiratory failure, apnea and sudden death. PMID- 11759378 TI - [The minimally invasive approach--to where will it lead?]. PMID- 11759377 TI - [Is drinking alcohol good for your health?]. AB - Numerous epidemiological studies have disclosed documented evidence that light to moderate consumption of any alcoholic beverage is associated with approximately 20% reduction in cardiovascular disease risk. This finding applies to both men and women and to healthy individuals as well as those with coronary heart disease, diabetes, hypertension, or heart failure. Nevertheless, the issue of including a recommendation for mild to moderate alcohol consumption within the routine recommendations for primary and secondary prevention of coronary heart disease is still controversial. The controversy is derived partly from methodological issues and partly from documented adverse health effects of excessive alcohol drinking. The key issue is the definition of the optimal dose of alcohol which guarantees a positive benefit-risk ratio, i.e. enjoying the benefits of alcohol without substantial risk. The accumulating scientific evidence shows that a daily consumption of less than 30 grams of alcohol for men and less than 15 grams for women is compatible with the above goal and is not associated with health risks. Therefore, for most individuals it is appropriate to recommend mild to moderate alcohol consumption as part of a healthy life style for the prevention of cardiovascular disease. Recommendations should be given on an individual basis, taking into account the patient's age, gender, physical and mental health status, personality and past drinking habits. The desirable quantity and its upper limit as well as drinking patterns should be clearly defined. All persons should be warned to avoid heavy drinking. Awareness of indications for abstinence from alcohol such as pregnancy, sport activity and the use of certain medications is highly important. PMID- 11759379 TI - [Hormonal replacement therapy and inflammatory response--update]. AB - Recent studies have shown that the administration of hormonal replacement therapy (HRT) to postmenopausal women might be associated with the appearance of increased concentrations of C-reactive protein (CRP). This marker of inflammation might be associated with an unfavorable outcome regarding the appearance of ischemic vascular diseases and accelerated atherosclerosis in elderly women. In addition, the use of HRT might be associated with an enhanced thrombotic tendency. Therefore, the administration of HRT to individuals who have increased concentrations of inflammatory markers (CRP for example) and/or thrombophilic ones, might be associated with an eventual less favorable clinical outcome. PMID- 11759380 TI - [The mosaic of pemphigus]. AB - Pemphigus is an autoimmune blistering disease of skin and mucous membranes. The classic types of pemphigus are pemphigus vulgaris and pemphigus foliaceus. In this review we summarize recent advancement in the etiology and the pathogenesis of pemphigus. Desmogleins--transmembrane glycoproteins involved in intracellular adhesion--were recognized as targets of pemphigus antibodies. It was found that the distribution and the expression of desmogleins can explain the difference in the localization of lesions in pemphigus vulgaris and pemphigus foliaceus. Pemphigus develops in a two-step process. The first step leads to the presence of a low titer of autoantibody, the second step results in a significant increase in the antibody titer which causes the clinical stage of the disease. Selective presentation of self peptides can explain the Major Histocompatibility Complex (MHC)--linked susceptibility to autoimmune diseases including pemphigus and rheumatoid arthritis. Peptides selective for the disease-associated molecules can be identified and used to search for microbiologic factors that can take part in the pathogenesis of pemphigus. PMID- 11759381 TI - [The safety of new quinolone treatment--levoflaxacin (tavanic) and moxiflocacin (megaxin)-- in the community]. PMID- 11759382 TI - [Eosinophilia as an unfavorable prognostic factor for clozapine-induced severe adverse side-effects]. PMID- 11759383 TI - [Micronutrient (vitamins and minerals) supplementation for the elderly, suggested by a special committee nominated by Ministry of Health]. AB - The elderly tend to be at a higher risk for nutritional deficiencies and in particular for micronutrient deficiencies. A committee nominated by Ministry of Health examined the relevant literature and the local recommendations as well as the recommendations from other countries and suggested a daily special micronutrient supplementation for institutionalized elderly. The preparatory will contain about half the RDA for most of the micronutrients, except for fluorine that is recommended at a lower level and biotin, vitamins D, C, B12 as well as zinc, copper and molybdenum at a level higher than half the RDA. Major elements such as calcium, are not included in the preparatory and would be supplied separately when needed. Vitamin K and iron are excluded as well. The suggested preparatory composition, mg: vitamin A, 0.450; vitamin D, 0.015; vitamin E, 10; thiamin, 0.6 Pound riboflavin, 0.7; biotin, 0.030; pantothenic acid, 3; niacin, 8; vitamin C, 60; vitamin B6, 0.8; folic acid, 0.120; vitamin B12, 0.0024; choline up to 275; zinc, 8; copper, 0.9; fluorine, 0.5; manganese, 1.2; chromium 0.020; molybdenum, 0.045; selenium, 0.030; and iodine, 0.075. Fat-soluble vitamins should be microencapsulated. Micronutrient supplementation is part of Ministry of Health balanced nutrition policy. The committees recommendations are also applicable for the free-living elderly. PMID- 11759384 TI - [What's new in the hippocampus? Neurons regenerate in the adult brain]. AB - Since the late 1960's, the production of new neurons was known to occur in the brains of adult rodents however, only recently, neurogenesis was documented in the hippocampus of adult mammals. This region in the brain is related to the function of learning and memory. Hence, the finding that in response to training on associative learning tasks that require the hippocampus the number of newly generated neurons increases, could be highly significant. PMID- 11759385 TI - [Microarray technology--clinical aspects]. PMID- 11759386 TI - [Methods for core temperature measurements]. AB - The measurement of core temperature is important for many clinical situations including heat illnesses, hypothermia, infections, sepsis, shock, hemorrhage, and exposure to chemical and biological agents. Currently, oral and rectal temperatures are clinically utilized for such measurements. However, oral measurements are not always possible and accurate whereas rectal measurements are not convenient in the field, are labor intensive, use fragile glassware containing mercury--an environmental contaminant, require sterilization and are not suited for mass casualties. A simple, non-invasive, non-breakable, inexpensive device to measure core temperature, which is not labor intensive, would have great use in the field and in hospitals, as well as provide an important advance in instrumentation for experimental physiology. The purpose of this work is to evaluate the different methods for core temperature measurement. Since the middle of the 18th century, the mercury thermometer has been almost the only instrument for measuring core temperature. Today, more sophisticated methods and instruments are gaining popularity. In addition, new promising converted techniques, which are about to enter the market and increase the available variety of instruments, might improve the situation as far as reliability and convenience of use are concerned. Despite the importance and usage of this variable, the progress in this field has been slower than would have been expected. PMID- 11759387 TI - [Pacing mode influence on morbidity and mortality]. AB - It is widely believed that physiologic pacing (defined as atrial or atrioventricular synchronous pacing) reduces cardiac morbidity and mortality and is associated with improved quality of life compared to ventricular pacing. In this review we present data from three large prospective trials (PASE, CTOPP, MOST) comparing physiologic pacing to ventricular pacing. The prospective trials report that physiologic pacing is associated with a reduced risk of developing chronic atrial fibrillation over time and improved quality of life in patients with sinus node disease compared to ventricular pacing. However, these trials failed to demonstrate that physiologic pacing reduces heart failure, thromboembolism, or cardiac death compared to ventricular pacing. Based on the available clinical trials, physiologic pacing is not indicated in patients with a short life expectancy. Physiologic pacing should be considered for younger patients (age < 75 years), patients likely to be pacemaker dependent, and patients for whom maintenance of sinus rhythm is desirable, i.e., patients with ventricular hypertrophy and diastolic dysfunction who are most likely to be severely symptomatic if AV synchrony is lost. PMID- 11759388 TI - [Generic antiarrhythmics: safety and efficacy versus cost]. PMID- 11759389 TI - [Cautious gait and fear of falling in the elderly]. AB - Falls are common in the elderly, and fear of falling is widely prevalent. This review emphasizes some of the defensive adaptations that occur in relation to concern about balance, and the phenomenon of cautious gait and fear of falling. Fear of falling affects those who never fall as well as those who do. Anxiety and fear can profoundly influence motor performance, resulting in a timid gait. However, fear of falling can take a more pathological turn and negate its survival value. Comorbid conditions associated with fear of falling appear to be similar to those responsible for falls. A fall evaluation should always include an assessment of fear of falling. All these conditions should be viewed as reversible causes of gait failure in the elderly. A number of interventions can help alleviate fear of falling and improve confidence. PMID- 11759390 TI - [Groin pain in sport]. AB - Pain syndromes in the groin are common in people involved in sports such as soccer, handball etc. Approximately 2.5% of all sport related injuries are in the pelvic area. Soft tissue injuries are the most common cause for groin pain in athletes. The majority of conditions will gradually disappear with rest and symptomatic treatment. Symptoms are often vague and diffuse. Therefore, high index of suspicion, thorough knowledge of the anatomy and multidisciplinary approach is needed for diagnosing and treating. Early diagnosis will reduce morbidity. Managing chronic pain is difficult. Groin injuries are some of the most challenging injuries in the field of sports medicine. PMID- 11759391 TI - [Role of caspases in neural degeneration in amyotrophic lateral sclerosis]. AB - Animal model of the motor neuron disease amyotrophic lateral sclerosis (ALS), has implicated apoptotis in the neuronal degeneration evident in this disease. Mice showing ALS-like symptoms, as well as several human families with ALS, have a missense mutation in the gene coding for DOD-1. A defective enzyme enhances neuronal cell death by activating interleukin converting enzyme (ICE), an initia of apoptosis. The role of caspase-1 and caspase-3 in the apoptotic process is apparent and the use of the caspase inhibitor zVAD-fink demonstrated some promise in slowing neural death by apoptosis and prolonging life in mice with ALS-like symptoms. We discuss the possible mechanisms of caspase enzymes cascade activation and their central role in apoptosis and possibly in neural death. PMID- 11759392 TI - [Animal cruelty--ethical and halacha view]. PMID- 11759393 TI - [Historical evidence of the beginning of modern medicine in the holy land: "list of medicinal preparations found in stores and dispensary on july 21st 1857"]. AB - The London Society for Promoting Christianity Amongst the Jews established the first Western hospital in Jerusalem in the middle of 19th century. It was built for the benefit of the Jewish population of the city, and it transposed the Holy Land, from a medical point of view, to the modern era. The huge archives of the London Society in England contain many documents dealing with its activity. One document, revealed here for the first time, describes the content of the medicinal preparations held in the stores of the British hospital and dispensary in Jerusalem on July 21 1857. The list, presented here in full, is impressive in its length, containing hundreds of medicinal substances originating from plants, minerals, and animals that were used in the Western world at the time. Most of the chemicals in the list had never previously appeared in any published historical source concerning Palestine. The list is thus one of the first pieces of evidence of modern medical and pharmacological activities in the Holy Land. A comparison of the list with several other 19th century lists of medicinal substances found in professional literature revealed that it contains most of the known medicinal substances of that time. Compared with medieval documents, or lists of traditional substances compiled a few years earlier, the 1857 list is richer and contains new substances and preparations originating in the New World (America) and chemicals unknown in the region before. It is evidence of the change that occurred in the field of pharmacology owing to the penetration of the modern medicine into the Holy Land. The 1857 list contains 268 substances: 147 medicinal preparations of plant origin, 117 preparations of chemical and mineral origin, and only four of animal origin. PMID- 11759394 TI - [Thermoregulation in rest and exercise--gender differences]. PMID- 11759395 TI - [A new reality--epidemiology of terror]. PMID- 11759396 TI - [The 2001 Nobel Prize of Medicine]. PMID- 11759397 TI - [Laryngeal tuberculosis is not such a rare disease]. AB - Laryngeal tuberculosis used to be the most common disease of the larynx at the beginning of the 20th century. As the incidence of tuberculosis decreased, laryngeal tuberculosis almost disappeared. The increase in the incidence of tuberculosis during the last two decades was accompanied by an increase in the incidence of laryngeal tuberculosis. Laryngeal tuberculosis is characterized by a wide variety of symptoms ranging from a process restricted only to the larynx, to a multiple system disease. The laryngeal findings are not specific and may imitate other chronic diseases and tumors of the larynx. This complexity encumbers diagnosis. In this study, we describe the changes in the population effected, the means of transmission and the appearance of laryngeal tuberculosis during the 20th century. We present the case histories of three patients exemplifying the existing variety in the clinical appearance of laryngeal tuberculosis. PMID- 11759398 TI - [Adrenergic innervation of the myocardium in patients with cardiac syndrome X]. AB - 11 syndrome X patients and 8 healthy controls were investigated by myocardial scintigraphy (SPECT) with 123-I-MIBG. Regional defects in cardiac 123-I-MIBG uptake were found in 90% syndrome X patients. Total cardiac 123-I-MIBG uptake appeared significantly higher in syndrome X patients. Perfusion defects on stress 99m-Tc-MIBI scintigraphy were found in 10 syndrome X patients who had also abnormal 123-I-MIBG scintigrams. It is suggested that impairment of efferent cardiac adrenergic nerve fiber function in syndrome X patients may contribute to pathophysiologic and clinical features of syndrome X. PMID- 11759399 TI - [Differential diagnosis of infectious and non-infectious thrombotic endocarditis]. AB - The aim of the study was analysis of clinical and laboratory markers of non infectious thrombotic endocarditis (NITE) to facilitate differential diagnosis with infectious endocarditis (IE). 20 NITE patients (8 males and 12 females, mean age 32.3 years) were included in the trial. They had primary antiphospholipid syndrome, secondary antiphospholipid syndrome in systemic lupus erythematosus, nodular polyarteritis, nonspecific aortic arteritis, paraneoplastic NITE in lung and stomach cancer. NITE was also diagnosed in patients with gout and ankylosing spondylarthritis. Clinical and laboratory findings allow to differentiate IE with NITE. The former is characterized by destructive valvular lesions registered at echo-CG, positive hemoculture and arterial embolism. As a rule, NITE is associated with antiphospholipid syndrome and manifests with arterial and venous thrombosis, thrombocytopenia, livedo and presence of antibodies to cardiolipins. PMID- 11759400 TI - [Immune and interferon system in patients with bronchial asthma]. AB - We studied the levels of acute inflammation phase proteins (AIPP), production of alpha, gamma and serum interferons, the activity of epsilon-receptors of T lymphocytes in 39 patients with bronchial asthma (BA). Correlations were made with the process severity and basic therapy. We discovered imbalance of immunoregulatory mechanisms: enhanced AIPP synthesis, low production of induced alpha and gamma interferons, elevated concentrations of poor-differentiated T lymphocytes. This confirms persisting inflammation in BA. PMID- 11759401 TI - [The assessment of meteorological sensitivity of patients with circulation disorders and therapeutic-prophylactic effect of impulse baro-training]. PMID- 11759402 TI - [Comparison of flow-volume curve parameters in patients with respiratory sarcoidosis and chronic non-specific pulmonary diseases]. AB - 62 patients with respiratory sarcoidosis (RS) and 50 patients with chronic nonspecific pulmonary diseases (CNSPD) inhaled 1 ml (250 mg ipratronium bromide and 500 mcg phenoterol hydrobromide) berodual by means of nebulizer. 68% of the examinees responded with obstruction of the distal part of the respiratory tree. RS causes partially reversible defects in permeability, primarily at the level of small bronchi. Berodual-induced changes in the curve flow-volume in RS differed from those in CNSPD patients by the absence of a rise in the exhalation power. Lofgren's syndrome deteriorated reversibility of bronchial permeability defects in RS patients. Smoking effects on bronchial permeability and reversibility of relevant defects in RS patients were insignificant. Pathogenesis of reversible obstruction in sarcoidosis demands further studies. PMID- 11759403 TI - [Somatoform disorders in ulcers]. AB - We studied correlations between psychoemotional and vegetative disorders in ulcer. 60 patients with ulcer varying in severity were examined. The severity was judged by the disease history, endoscopic and x-ray findings. Emotional and personality characteristics were evaluated by answers in special questionnaires, vegetative deviations were studied with special tests, scale, cardiointervalogram. It was found that more severe course of ulcer correlated with growing vegetative dysfunction. The progressive ulcer course ran with predominance of sympathetic autonomic nervous system and is accompanied with marked psychoemotional tension and development of anxiodepressive personality traits. PMID- 11759405 TI - [Somatic vascular and psycho-emotional disorders in some gastrointestinal diseases and the correction with physical factors]. AB - Vegetovascular disorders are obligatory and even leading clinical manifestations of chronic gastrointestinal diseases. Physiotherapy in combination with psychotherapy produce a normalizing effect on functional-morphological condition of the gastrointestinal organs, correct alterations in the neuropsychic sphere and autonomic nervous system. PMID- 11759404 TI - [Adrenal ACE and type II glucocorticoid receptors in primary hyperaldosteronism]. AB - Adrenal tissue from 6 patients with primary hyperaldosteronism has been examined for the presence of angiotensin-converting enzyme (ACE). Its activity and amount of glucocorticoid receptors of type II (GR-II) were measured. ACE and GR-II were detected in adrenal tissue. GR-II induce ACE activity in interaction with plasma hydrocortisone. The glucocorticoid-receptor mechanism is an essential element in regulation of ACE activity determining a vasopressor effect. Disclosed is one of the aspects of tissue renin-angiotensin system function in primary hyperaldosteronism. PMID- 11759406 TI - [Skin micro-hemangioma]. AB - Microhemangiomas (MHA) observed on the skin are known under different terms: Tuzhilin's "red drops", senile hemangiomas, Campbell de Morgan spots, scrotal angiokeratomas Fordyce-Satton. Examination of 46 healthy subjects and 241 patients aged 15 to 76 years having different diseases has found that MHA occur both in healthy subjects and patients with different diseases. The number and size of MHA increase with age. The condition seems inheritable. Histologically, MHA are cavernous hemangiomas with thick connective tissue septa making impossible MHA dehematizing in diascopy. The conclusion is made on diagnostic insignificance of skin MHA. PMID- 11759407 TI - [Pathogenesis and treatment of cardiac failure in dilated cardiomyopathy]. PMID- 11759409 TI - [Hypnotics: problems and achievements]. PMID- 11759410 TI - [Immunological reactivity and autoimmune disorders in patients with chronic gastrointestinal diseases]. PMID- 11759408 TI - [The effectiveness of intravenous form of Nitro Mac in patients with acute left ventricular failure and functional class III angina]. AB - Efficacy of intravenous drop Nitro Mac (alcoholic solution of nitroglycerin) in acute left ventricular failure and angina of functional class III was investigated in 18 patients aged 42-68 years. 1 ml Nitro Mac solution was diluted in 100 ml isotonic solution once a day (in severe condition twice a day) for 6 days. Nitro Mac relieved anginal attack on infusion minute 3-5 and anginal pain on minute 2. In angina functional class III Nitro Mac completely eliminated anginal attacks in 8 of 10 patients and reduced its number in 2 patients. Exercise tolerance has grown. Oral nitrates' doses could be decreased twice. Side effects were mild. Nitro Mac is recommended for treatment of acute cardiac failure and angina of functional class III as an effective medication. PMID- 11759411 TI - [Back to the problem of chronic pancreatitis]. PMID- 11759412 TI - [A complicated case of diagnosis of ileo-cecal tuberculosis]. PMID- 11759413 TI - [A case of gastric phytobezoar]. PMID- 11759414 TI - [Arterial hypertension: topical issues]. PMID- 11759415 TI - [On teaching some key points of diagnosis of internal diseases]. PMID- 11759416 TI - [Lexical-semantic aspects of Russian medical terminology of the 18th century]. PMID- 11759417 TI - [Effects of antihypertensive drugs of lipid metabolism. Part II. Antihypertensive therapy]. PMID- 11759418 TI - Evidence-based practice: fad or functional paradigm? PMID- 11759419 TI - Evidence-based nursing practice: why is it important? AB - Evidence-based practice has gained momentum in nursing, and definitions vary widely. Research findings, knowledge from basic science, clinical knowledge, and expert opinion are all considered "evidence"; however, practices based on research findings are more likely to result in the desired patient outcomes across various settings and geographic locations. The impetus for evidence-based practice comes from payor and healthcare facility pressures for cost containment, greater availability of information, and greater consumer savvy about treatment and care options. Evidence-based practice demands changes in education of students, more practice-relevant research, and closer working relationships between clinicians and researchers. Evidence-based practice also provides opportunities for nursing care to be more individualized, more effective, streamlined, and dynamic, and to maximize effects of clinical judgment. When evidence is used to define best practices rather than to support existing practices, nursing care keeps pace with the latest technological advances and takes advantage of new knowledge developments. PMID- 11759420 TI - Posing clinical questions: framing the question for scientific inquiry. AB - Much of nursing practice is (and always has been) based on information generated through inquiry. Finding the best answers quickly and effectively for the questions that arise in the clinical setting facilitates care, increases nursing efficiency, and improves patient outcome and satisfaction. Posing clinical questions also can help nurses identify and fill in gaps in knowledge, keep up with advances in clinical practice, and strengthen interactions with their peers, team members, and patients and their families. Formulating clinical questions that lead to sound, evidence-based answers to resolve clinical problems or direct patient-care decisions takes time and practice. The information in this article will assist nurses to develop the skill of framing clinical questions efficiently and effectively. PMID- 11759421 TI - Integrating clinical reasoning and evidence-based practice. AB - Evidence-based practice involves basing clinical decisions and practice on the best available evidence. What do nurses need to think about when seeking to pursue evidence-based practice? What challenges do practitioners face in blending clinical reasoning with evidence-based practice? In this article, the authors argue against basing clinical practice on narrow definitions of evidence, relying solely on experimental findings or, even more exclusively, on randomized controlled trials. Instead of defining best practice narrowly by the strength of the current empirical evidence used to guide clinical decisions, it should be defined broadly by what is the best information to use to make decisions for a given patient in a particular setting. Credible and accountable clinical decisions rely on a number of forms of knowledge and evidence. This evidence includes findings from across the range of research methods, including experimental, interpretive, and action research. In nursing, it also includes evidence that has arisen from the depth of practice knowledge of expert clinical nurses. Professionals, particularly advanced and expert clinicians such as critical care nurses, use clinical reasoning to guide their practice in the uncertainty of clinical practice contexts. This reasoning helps the nurse make judgments about the relevance of particular research and clinical evidence for a specific patient and setting. PMID- 11759422 TI - Champions for evidence-based practice: a critical role for advanced practice nurses. AB - Evidence-based practice is emerging as a widely accepted paradigm for contemporary professional nursing practice. Institutions and providers of healthcare services are adopting this framework to guide the structure, process, and outcomes of patient care delivery. Advanced practice nurses are ideally prepared and positioned within healthcare delivery systems to champion the integration of this practice as a model for evidence-based patient care. This article highlights opportunities and suggests strategies for advanced practice nurses to serve as catalysts for optimizing patient care through evidence-based practice. PMID- 11759423 TI - Teaching advanced practice nursing students how to use the Internet to support an evidence-based clinical practice. AB - In the past decade, clinicians have dramatically increased their use of the Internet as an information resource to guide clinical practice. The amount of evidence-based information on the World Wide Web (WWW) is growing at an explosive rate. Although the term "Internet" actually refers to the wires that link computers, and the term "World Wide Web" refers to the linked information, these terms will be used interchangeably in this article. Advanced practice nurses (APNs) need to learn how to locate evidence-based information efficiently on the Internet, how to evaluate the validity and relevance of the information, and how to use the information to support their practice decisions. This article describes a research course that the author teaches to APN students at the University of San Francisco School of Nursing. The course was designed to improve students' skills in using the Internet to support an evidence-based clinical practice (EBCP). The information in this article can assist nurse educators in teaching their APN students how to locate and evaluate evidence-based information on the Internet. It also can assist practicing APNs in using the Internet to facilitate an EBCP. PMID- 11759424 TI - Resources to enhance evidence-based nursing practice. AB - Evidence-based practice means integrating the best available research evidence with information about patient preferences, clinician skill level, and available resources to make decisions about patient care. Barriers to the use of research based evidence occur when time, access to journal articles, search skills, critical appraisal skills, and understanding of the language used in research are lacking. Resources are available to overcome these barriers and support an evidence-based nursing practice. This article highlights available resources and describes strategies that nurses can use to develop and sustain an evidence-based nursing practice. PMID- 11759425 TI - Systematic reviews: the heart of evidence-based practice. AB - Research utilization approaches in nursing recently have been replaced by evidence-based practice (EBP) approaches. The heart of the new EBP paradigm is the systematic review. Systematic reviews are carefully synthesized research evidence designed to answer focused clinical questions. Systematic reviews (also known as evidence summaries and integrative reviews) implement recently developed scientific methods to summarize results from multiple research studies. Specific strategies are required for success in locating systematic reviews. Major sources of systematic reviews for use by advanced practice nurses in acute and critical care are the Online Journal of Knowledge Synthesis for Nursing, Agency for Healthcare Research and Quality, and the Cochrane Library. This discussion describes systematic reviews as the pivotal point in today's paradigm of EBP and guides the advanced practice nurse in locating and accessing systematic reviews for use in practice. PMID- 11759426 TI - Meta-analysis: a tool for evidence-based practice. AB - Evidence-based practice rests on the knowledge generated from sound empirical research combined with clinical expertise. However, many clinicians lack the time to evaluate multiple studies. Meta-analysis is a statistical procedure for combining the results of multiple studies investigating a common problem or issue to produce a pooled effect size, and to evaluate the efficacy of interventions across studies. Meta-analysis can thus be used to synthesize and integrate empirical research to provide important evidence for best-practice decisions. This article examines the meta-analysis process and its links to evidence-based practice. PMID- 11759427 TI - Biostatistics and study design for evidence-based practice. AB - The hallmark of an evidence-based practitioner is one who reflects on their clinical decision making and uses research evidence to reduce clinical uncertainty and guide their practice. Understanding how the results of empirical research can be appropriately integrated into clinical practice requires a basic understanding of study design and statistical analysis. This article provides an overview of some of the key concepts related to study design and statistical inference that are important to accurately measure clinical outcomes and to appropriately interpret the results of studies within the context of evidence based decision making. PMID- 11759428 TI - Finding evidence: refining literature searching skills for the advanced practice nurse. AB - With increasing interest in evidence-based healthcare, nurses are finding the need to improve skills in locating current, valid evidence to support clinical practice. Because of the holistic nature of nursing, gathering evidence requires searching a variety of sources within many different scientific disciplines. The diverse nature of this task requires effective skills for finding information from both print and electronic sources. This article identifies informational databases available to advanced practice nurses, reviews search terminology, and suggests practical strategies for successful database searches in support of evidence-based practice. PMID- 11759429 TI - Evidence-based nursing Web sites: finding the best resources. AB - Evidence-based nursing is becoming an increasingly widespread phenomenon in the nursing profession. As the evidence-based nursing movement grows, the Internet/World Wide Web has become a vital information link for keeping pace with current science and medical advancements. This article describes Internet resources currently available to support evidence-based nursing practice, presents practical search methods for locating these resources, and suggests criteria for evaluating the "evidence" available on the Internet. Results of an Internet search for Web sites that met the proposed criteria for support of an evidence-based nursing practice located only three sites. The sites are described and evaluated for their usefulness. The authors demonstrate that although many Internet resources are available to nurses, few sites provide information or evidence supported by valid research. PMID- 11759430 TI - Online journals: access and support for evidence-based practice. AB - Online journals are one of the tools useful to nurses in providing patients with evidence-based nursing care. Available 24 hours a day and capable of including manuscripts of nearly unlimited size, these journals expedite dissemination of information to readers by both their electronic format and the changes that can be made to shorten the publication process. They are, however, subject to the same requirements for critique applicable to print journals, requirements that are essential in evaluation of evidence for practice. PMID- 11759431 TI - Evidence-based pediatric nursing: does it have to hurt? AB - Pediatric nursing is deeply rooted in tradition and ritual. Although many practices remain relevant, others do not stand up to the challenge of an evidence based nursing practice. Though intuition and tradition are important aspects of professional nursing practice, their incorporation into clinical practice can vary among practitioners. Although ample evidence to guide the practice of pain assessment and pain management in children exists, children remain undermedicated when compared to adults. This article explores the influence of practice traditions, personal bias, and the persistence of myths regarding pain in children on the practice of pain relief. PMID- 11759432 TI - Quality care outcomes in cardiac surgery: the role of evidence-based practice. AB - An internal database and research methods were used to evaluate the impact of clopidogrel on cardiac surgical bleeding. This quality improvement initiative, led by the clinical nurse specialist, showed that preoperative exposure to clopidogrel was associated with significant increases in chest tube output, blood product use, and reoperation for bleeding rates that were 10-fold higher than for control patients (0.85% versus 8.3%, P = 0.027). Acute care costs averaged $2,680 more for patients who received clopidogrel (P = 0.1936). After implementation of an interdepartmental clinical practice guideline, preoperative exposure to clopidogrel dropped from 39% to 6.3% (P = 0.0000). This drop was accompanied by reductions in chest tube output, blood product use, and bleeding complications, with improved achievement of clinical benchmarks. The availability of internal evidence to support achievement of best practices was an essential factor in the implementation of this interdepartmental change. Comprehensive database systems and advanced practice nurses are highlighted as essential components of evidence based programs. PMID- 11759434 TI - Bioterrorism vs. acceptable risk. PMID- 11759433 TI - Evidence-based practice centers: production of evidence report on management of atrial fibrillation. AB - Healthcare practitioners are increasingly expected to understand and practice evidence-based healthcare. However, to apply evidence-based healthcare methods on an individual basis in a specific clinic or with a specific patient is rarely possible because it is time consuming and requires specialized skills. One way of facilitating evidence-based care is to use evidence-based products produced by others. In 1997, the Agency for Healthcare Research and Quality designated 12 evidence-based practice centers. Since their inception, these evidence-based practice centers have produced 40 evidence reports. This article provides an overview of the purpose and process of evidence-based practice centers using examples from the first evidence report produced by the Johns Hopkins Evidence based Practice Center. The steps in the process of developing an evidence report include recruitment of experts, refinement of the questions, design of the literature search plan, quality assessment and data abstraction from identified articles, synthesis of evidence, peer review, and dissemination. Each step is defined and illustrated with examples from the development of an evidence report on atrial fibrillation. PMID- 11759435 TI - Anthrax: a primer for practitioners. PMID- 11759436 TI - Anthrax vaccine: what you need to know. PMID- 11759437 TI - Management pearls for chemical and nuclear terrorist attacks. PMID- 11759438 TI - Smallpox: elimination or possible re-infection? PMID- 11759439 TI - Post-traumatic stress disorder in the age of terror. PMID- 11759440 TI - Cyberterrorism: bytes, not bombs. PMID- 11759442 TI - Terror in the age of 24-hour news. PMID- 11759441 TI - Chemical and biological warfare in Afghanistan. PMID- 11759443 TI - September 11, 2001: how one local health department coped with the threat. PMID- 11759444 TI - Training for hospital emergency preparedness. PMID- 11759445 TI - Skin, sun and secondary students. PMID- 11759446 TI - What to do with the offending bird. PMID- 11759447 TI - Regional nerve block series. PMID- 11759448 TI - Calcium antagonists as first line antihypertensive therapy. PMID- 11759449 TI - Postnatal depression and health care use. PMID- 11759450 TI - Diagnosis in dermatology. Tricks of the trade. AB - BACKGROUND: Many medical practitioners find difficulty in diagnosing common skin conditions. This may translate into difficulty in management when treatment may have to be prescribed without a specific diagnosis. OBJECTIVE: To develop a simplified approach to diagnosis of the common skin conditions, using major discriminators on history and examination. DISCUSSION: By simplifying the history and examination, it is possible to categorise responses to questions or key signs on examination in a way that should assist in the diagnosis of common skin conditions. But, as always, when a condition cannot be fitted into the model, consider a specialist opinion. PMID- 11759451 TI - Management of psoriasis. AB - BACKGROUND: Psoriasis affects more than 6% of Australian adults. While rarely life threatening it can have an enormous psychosocial impact on sufferers. OBJECTIVE: To outline the treatment options for psoriasis. DISCUSSION: Localised psoriasis can usually be managed by topical therapy but more widespread psoriasis will require stronger treatments such as ultraviolet light, or various oral therapies. There is a great deal of psoriasis research underway and a number of new treatments have evolved over the past few years, some of which have yet to be released in Australia. As with any medical therapy the risks of the treatment must be weighed against the likely benefits. The patient needs to have an informed, sympathetic doctor to discuss the various available options. PMID- 11759452 TI - Acne. Myths and management issues. AB - BACKGROUND: Acne is one of the commonest dermatological problems, experienced by approximately 80% of Western adolescents. If left untreated it can be the source of significant physical sequelae and psychological problems. Prevalence studies show that acne is not just a problem of youth but for some, it persists into middle age. OBJECTIVE: To review both the causes of acne and current acne management issues in relation to problems and options for improving outcomes. DISCUSSION: The earlier acne is treated the more likely scarring will be minimised, so a proactive approach is important. The development of oral isotretinoin has offered those with severe, nodulocystic acne the chance of not only disease containment but suppression. However, it is still the only available treatment that targets all four pathological processes involved in acne. The development of antibiotic resistance is becoming a global problem and causing a need to revise our approach to acne. PMID- 11759453 TI - Patient education sheet. How common is acne? PMID- 11759455 TI - Parkinson disease and its differentials. Diagnoses made easy. AB - BACKGROUND: Parkinson disease is a common neurological disorder that is both underdiagnosed and inaccurately diagnosed. There is no reliable biological marker or test that can differentiate between causes of parkinsonism. Even for experienced clinicians, the clinical diagnostic accuracy compared to post mortem findings is about 80%. OBJECTIVE: To discuss the clinical features that differentiate Parkinson disease from other important causes of parkinsonism. DISCUSSION: Although Parkinson disease is a common cause of parkinsonism, other candidates such as drug reactions, benign essential tremor, vascular disease and Lewy body dementia need to be differentiated. Incorrect diagnosis can result in complications related particularly to the use of levodopa and antipsychotic agents. Diagnostic accuracy is important to ensure appropriate management, to avoid complications and to assist patients to have realistic expectations and prognostic information about their condition. PMID- 11759454 TI - Rashes in infants. Pitfalls and masquerades. AB - BACKGROUND: Physiological and pathological skin eruptions are extremely common in neonates and are often presented to the general practitioner as either a primary or incidental problem at consultation. OBJECTIVE: To discuss the presentation and treatment of common dermatological conditions presenting in the first six months of life. DISCUSSION: Common conditions such as pityrosporum folliculitis, neonatal acne, cradle cap, eczema and food allergy are discussed. The rarer conditions of zinc deficiency and neonatal lupus are described because they may pose significant potential medical consequences. PMID- 11759456 TI - Travel insurance. AB - In this article are salutory and awful stories, all based on true cases. They serve to illustrate how terrible the problems can be when travel insurance is not appropriately secured before a traveller becomes sick, or where the patient assumes the risk himself, without insurance, in the absence of a proper understanding of the consequences. PMID- 11759457 TI - Dementia. Strategies for caring. PMID- 11759458 TI - Regional nerve blocks. Part 7--Intercostal nerve blocks. AB - This is the seventh in our series of regional nerve blocks. This month we outline a useful block for a variety of in-hospital/clinical applications. PMID- 11759459 TI - Skin flaps. PMID- 11759460 TI - Adverse effects associated with herbal medicine. AB - Medical journals are now publishing case reports of adverse reactions to herbal therapy. With increasing use, and more importantly, increasing awareness of potential hazardous effects, these reports are liable to increase in frequency. It is also increasingly realised that herbs and drugs can interact in the same way that drug/drug interactions occur. This is particularly hazardous for the patient if the treating doctor is not aware of the herbal prescription. This article reviews the published material and highlights areas of major concern. Most of the serious adverse events reported relate to problems of product quality or adulteration. PMID- 11759461 TI - Early medical registration in Australia. Part 2. AB - The lure of land and gold, the hope for better health and an overcrowded profession in Britain led to an increasing number of doctors migrating to Australia. This migration was even more marked after the goldrush, especially in Victoria. The fifth article in this series looks at the way in which medical practice was controlled by excluding many of those doctors who were from non British origins. PMID- 11759462 TI - Publishing research in Australian Family Physician. PMID- 11759463 TI - The practice accreditation and improvement survey (PAIS). What patients think. AB - BACKGROUND: The Practice Accreditation and Improvement Survey (PAIS) is an endorsed instrument by the Australian General Practice Accreditation Limited (AGPAL) for seeking patient views as part of the accreditation of Australian general practices. METHOD: From September 1998 to August 2000, a total of 53,055 patients completed the PAIS within 449 general practices across Australia, which is about 8% of all Australian general practices. The validity and reliability of the PAIS instrument was assessed during the study. Patient views were also analysed via 27 items relating to doctors' interpersonal skills, access, availability and patient information. RESULTS: PAIS was found to have sound validity and reliability measures. Patient evaluations showed a range of scores for the 27 items (69-91%). Lower scoring areas were issues about access, availability and availability of information for patients. DISCUSSION: Users of general practice rate the doctors' interpersonal skills (capability) more highly than other practice service issues (capacity). There is, in patients' views, much more room for improving these capacity aspects of general practice. CONCLUSION: Future research should explore how practices act on the results of patient feedback, and which practice based strategies are more effective in raising standards of care from a patient's perspective. PMID- 11759464 TI - General practitioners and hospitals. Continuity of care. AB - BACKGROUND: The study aimed to improve continuity of care for patients undergoing major gynaecological surgery, by increasing their general practitioners' contact with the hospital and providing a comprehensive discharge summary. METHODS: Prospective randomised study of 200 patients admitted to a gynaecological oncology ward, and their GPs. Visits and telephone calls by GPs to hospital during their patients' admission were measured, with and without invitation and offer of payment for contact. A discharge summary was distributed. Postdischarge questionnaires surveyed patient satisfaction with care, confidence in future management by the GPs, and GP confidence in continuing patient care. RESULTS: Significant increases in contact rates by the GPs followed invitation. The discharge summary was not effectively distributed. No significant differences in patient satisfaction and confidence in future management by their GPs were found. General practitioners valued hospital contact most in meeting their patients' needs for information. CONCLUSION: Personal invitation increases GP contact with hospitals. While no statistically significant improvements in patient satisfaction or GP confidence were shown, the data suggested that GPs value contact to meet patient information needs. PMID- 11759465 TI - Consumer health information. What the research is telling us. AB - BACKGROUND: Consumer health information is a necessary component of patient care and consumer participation. OBJECTIVE: To outline the findings of the 'Assessing the Quality of Consumer Health Information Project' and discuss strategies for improving consumer information. DISCUSSION: The pamphlets identified in this study were not developed with consumer input with consequent deficits apparent. Providers and consumers appeared to use the information for very different purposes but both groups were critical of the ambiguous terminology and lack of quantified data. The provision of relevant information is a fundamental prerequisite of consumer participation in decision making in health care. Such information needs to be available, accurate, and understandable. PMID- 11759466 TI - Implementing a stronger patient safety program using the Internet takes step-by step planning. AB - Just over a year ago at the 104-bed Baylor Medical Center at Grapevine in Texas, supporting patient safety meant mostly relying on paper to get the job done. Now, it means going online to report adverse events and close calls--and promote patient safety. PMID- 11759467 TI - Taking a systemwide approach to improving quality care. AB - For the past decade, health insurer Anthem has been working with more than 300 hospitals in Ohio, Kentucky, and Indiana in a quality program designed to help them better use clinical data, monitoring, outcomes, and best practices to improve care in their facilities and promote patient safety. The results have been stimulation of new quality programs at the hospital level and a sense of partnership. PMID- 11759468 TI - Association promotes standardized care for heart patients through guidelines. AB - The American Heart Association has moved beyond just developing guidelines to implementing them for addressing inpatient treatments related to heart disease prevention. PMID- 11759470 TI - [Results of lengthening 20 humeri]. AB - PURPOSE OF THE STUDY: The aim of the retrospective study was to evaluate the results of 20 performed lengthenings of the humerus in children and adolescents. MATERIAL: Assessment involved totally 20 lengthening procedures having been done in 18 patients, twice as a repeated procedure, in the period 1983-1999. The indication was shortening of humerus approaching at least the amount of 50 millimeters. Proportion of boys and girls was 7/13. The shortening arouse on the base of pyogenic infection in 12, post-traumatically in 3, congenitally in 2 and in one case it was caused by a bone cyst expansion. Mean value of shortening was 83 millimeters. Mean value of age was 12 years, ranging from 7 till 16 years. METHODS: Lengthening procedure was performed by the use of different types of external fixation. In most cases Wagner unilateral fixator was used (13 cases). The choice of external fixator was based more on its availability determined by economical reasons. Contrary to Wagner and Orthofix, Ilizarov fixator did not need the common replacement of different sizes of apparatus during lengthening. Osteotomy was routinely performed at the point between the distal and middle thirds of the length of humerus, approach was always associated with visualisation of the radial nerve. RESULTS: Serial x-rays were consecutively studied to specify the mean value of lengthening--71 millimeters, the mean value of distraction phase--91 days, the mean value of total period of fixation--197 days and the mean value of period determined at its end by the full re canalisation of the lengthening zone--355 days. Mean value of bone lengthening index was calculated on 13.2 days/1 centimeter, mean value of bone healing index on 28.6 days/1 centimeter, and a modified bone healing index based on full recanalisation of the lengthening zone with a mean value of 44.5 days/1 centimeter. In no one case an additional bone grafting or plate osteosynthesis was necessary. Complications involved 3 cases of transient radial nerve palsy, which spontaneously resolved. DISCUSSION: As other reports of humerus lengthening respecting "callotasis method", this study showed almost uneventful distraction and healing This cohort involves a big sample of lengthenings resembling in its size the cohort of Cattaneo et al., the world's biggest group. CONCLUSIONS: It was proved, that the humerus lengthening is a safe method solving successfully the cosmetic problem of length deficiency. It seems, that presumably the keeping up the principle of "callotasis" brings about uneventful treatment programme. PMID- 11759469 TI - [Total hip joint replacement with the Walter type of prosthesis--long-term results]. AB - PURPOSE OF THE STUDY: The authors deal with the issues of loosening of Walter cementless total hip replacement. The intention was to develop the curve of survival of components of the implant and analyze the causes of their failure. MATERIAL: On the group of 127 patients on between 1988 and 1991 with the average follow-up of 9.4 years the authors operated analyze results of this type of implant which was applied in the whole main spectre of orthopaedic indications. METHODS: Based on the results survival curves were drawn by the method after Kaplan-Meier and they were compared from different views. RESULTS: Loosening requiring revision was recorded in 33 cases, a marked decline of the curve was evident after the fifth year. Ten-year survival was recorded in 66% of cups. The comparison of the implant survival diagram in patients operated on by different surgeons revealed the substantial impact of the surgical technique on the implant survival. Loosening of the stem was recorded in 16 cases. More than 80% of stems have survived ten years. DISCUSSION: As potential causes of the failure of the cup the authors consider errors in the surgical technique, excessive pitch of cup thread and material composition of the used alloy from which the primary series of cups was manufactured. The error was also caused by the indication of a conical cup in cases of oval defects solved by the combination of the cup and a solid homogenous bone graft (21% of loosened cups). In stem loosening the cause again consists in incorrect surgical technical and material composition of the used alloy. A marked improvement of the survival curve may be achieved by the stem surface finish in the form of a combined plasmatic hydroxyapatite coating. CONCLUSION: Results obtained from the preceding model of the Walter cup led to the change of the design of both the cup and the stem. The original titanium alloy VT6 was replaced by Tl6A14V ELI (Extra Low Interstitial) according to a more strict ASTM F136 standard. Osteointegration of both components has been improved by porous titanic surface combined with hydroxyapatite. PMID- 11759471 TI - [Duration of surgery in osteosynthesis of fractures of the trochanter]. AB - PURPOSE OF THE WORK: To analyze duration of surgery in individual types of internal fixation of fractures of the trochanteric massif and identify factors which have an impact on it. MATERIAL: Analysis covered a group of 137 patients treated with Ender nailing (EN), 314 patients by means of Dynamic Hip Screw (DHS), 74 patients by means of Gamma nail, 37 patients by means of Proximal Femoral Nail (PFN) and 13 patients by means of 130 degrees angled blade plate. The groups of patients included basicervical femoral neck fractures (29 cases), peritrochanteric and subtrochanteric fractures. Peritrochanteric fractures were evaluated according to Kyle classification, types I and II as stable (174 cases), type III unstable (159 cases) similarly as type IV (peri/subtrochanteric fractures or comminuted fractures of the whole trochanteric massif--35 cases). High subtrochanteric fractures (55 cases) were evaluated after Seinsheimer. From the viewpoint of AO/ASIF classification they were 31A1, 31A2, 31A3 fractures. EN was indicated mainly in Kyle I through IV fractures, DHS for basicervical fractures and Kyle I through III fractures, Gamma nail for Kyle I through IV fractures and high subtrochanteric fractures, PFN mainly for high subtrochanteric fractures and Kyle III fractures, 130 degrees angled blade plate was indicated only for stable peritrochanteric Kyle I fractures. RESULTS: The average duration of surgery, i.e. starting from the skin incision until the suture of the wound, was in DHS 47 min., in EN 52 min., in 130 degrees angled blade plate 54 min., in PFN 58 min. and in Gamma nail 70 min. The shortest time intervals were achieved in stable peritrochanteric fractures of Kyle I and II (EN, DHS, Gamma), the longest ones in high subtrochanteric fractures (Gamma, PFN). The impact of the learning curve was analyzed in DHS. In 1995 the average duration was 70 min. (35 patients/year), in 2000 already only 39 min. (123 patients/year). DISCUSSION: If we wish to make a serious evaluation of the duration of surgery of any method we must not forget that apart from it there is a whole number of other factors by which it is influenced. In case of proximal femur it is the type of fracture, the number and experience of surgeons, mastering the learning curve, annual frequency of surgeries at the respective Department as well as variation within the surgical technique (e.g. in DHS the number of distal locking and the number of locking screws, etc.) A significant role in this study was also played by the development of internal fixation at the Department of the authors. For instance, considerably shorter duration of surgery as well as minimum of complications in PFN were achieved thanks to mastering of the learning curve on the Gamma nail which we had started to use 3 years before. An objective evaluation requires also a sufficient number of cases in order to eliminate errors caused by low numbers and other variable factors. CONCLUSION: Surgery duration data which we present are comparable with the values included in the world literature. It applies not only to the duration of surgery in individual implants but also in individual types of proximal femur fractures. At present at our Department the average duration of surgery ranges in dependence on the applied implant, type of fracture and skills of the surgeon between 30 and 60 minutes. Relatively shortest duration can be achieved in DHS, in Gamma nail and PFN the duration is slightly longer. However, the duration of surgery is only a supporting factor. Of much greater importance for the patient is the quality of the surgery. Thus favouring any method only on the basis of the duration of surgery is absolutely irrelevant. PMID- 11759472 TI - [Effect of ultrasonic shock waves on the bone-bone cement interface]. AB - PURPOSE OF THE STUDY: Identification of the impact of ultrasound shock wave on the integration of bone cement in the bone and the examination of a potential application of this method in order to facilitate the extraction of cemented implants, mainly femoral component of total hip arthroplasty. MATERIAL: We used pig proximal femurs from which we made fragments involving approximately one third to one half of the profile of the bone and Palacos bone cement. METHOD: We made a groove in the cancellous bone, pressed bone cement with a wire loop in the cavity and let it harden. The samples were divided by random selection into two groups. Samples from A group were exposed to ultrasound shock waves and group B served as a control group. Then we measured the force needed for the extraction of the cement plug from the bone. RESULTS: Our measuring has shown an evident decrease of the force necessary for the extraction of the bone cement after the application of ultrasound shock wave. We did not find out any macroscopically evident damage of the bone cement or of the surrounding cortical bone. DISCUSSION: The results of our measuring are influenced by a different shape and size of the examined samples which also substantially differ from the situation when a stem of the endoprosthesis is implanted in the femoral canal and is surrounded by a cement mantle. As concerns risks associated with the application of the shock wave in this indication there is a risk of a fracture of the cortical bone around THR stem (the literature does not mention this complication) and a risk of the increase of pressure in the medullary cavity of the femur combined with a risk of fat embolism. In our view this increase of pressure is comparable with the effect of the implantation of femoral component. This method cannot be used for releasing cementless implants as the surrounding cortical bone gets damaged before the implant is released. CONCLUSION: Ultrasound shock wave is still used rarely in orthopaedics, however, the existing results are promising in many aspects. Of great importance is the fact that it is a non-invasive method. The field dealt with by this work covers only experiments in vitro but the results provide hope for a future clinical use. PMID- 11759473 TI - [The Pipkin fracture]. AB - PURPOSE OF THE STUDY: The authors present their experience in the treatment of fracture-dislocation of femoral head--the Pipkin fracture. MATERIAL: The group includes 11 patients treated in the period of 9 years (1991-2000). The average age was 46 years (range, 23-63 years). The average follow-up was 3.2 years (range, 6 months-9 years). According to the Pipkin classification four times we diagnosed Type 2, four times Type 3 (three times iatrogenic during closed reduction), three times Type 4. In 10 patients it was a case of a dashboard injury of drivers or passengers. In one patient it was industrial accident. METHODS: Ten patients were treated surgically, of which six times total hip arthroplasty was primarily used. In three patients we reconstructed the fracture with internal fixation, of this in two patients with Type 2 fracture the fragment from the head was fixed by two and three Krischner wires. In one patient the fragment of the head was extirpated. RESULTS: The evaluation after Thompson Epstein included only five patients as the patients treated by total hip arthroplasty were excluded. Good result was recorded four times and poor result once. DISCUSSION: As for diagnosis the authors recommend apart from standard radiographs also CT. The basis of the treatment of fracture-dislocations of femoral head is the reduction of the dislocated hip joint, optimally within 6 hours after the injury. A timely reduction prevents the onset of avascular necrosis of the femoral head. Another issue is the choice of an optimal surgical approach to the hip joint during the treatment of fracture of the Pipkin type. In all patients indicated to internal fixation or extirpation of the fragment the authors used anterolateral approach after Watson-Jones. CONCLUSION: In the conclusion the authors point out the possibility of the incidence of unfavourable third type of the Pipkin fractures during closed reduction of Types 1, 2 and 4. PMID- 11759474 TI - [Aprotinin (Antilysin Spofa)--its effect on decreasing hemorrhage in the postoperative period in hip arthroplasty]. AB - PURPOSE OF THE STUDY: Aprotinin is a non-specific inhibitor of serine proteases with hemostyptic and hemostatic properties. The effect covers suppression of fibrinolysis and support of the role of thrombocytes in coagulation. In a prospective randomized study we verified whether the application of aprotinin (Antilysin Spofa, Czech Republic) in the dosage effective in cardiosurgical patients reduces blood loss and the need for blood transfusion for orthopaedic patients. MATERIAL: 42 patients indicated to the primary THA were randomly selected into the study and control groups. Excluded were allergic patients and those who used aprotinin before. METHODS: Administration of 2.10(6) KIU of aprotinin was started preoperatively and is continued in the course of the first hour of surgery. In the operated on patients we recorded prior to operation and in the first post-operative morning the level of hemoglobin in blood and hematocrit, the number of infusions and blood transfusion units administered in the course of the surgery and in the post-operative period until the first post operative morning. We recorded blood loss in the period between the surgery and the first post-operative morning. Data acquired in the patients of the studied and control groups were compared by means of ANOVA test for repeated measuring and with the use of Mann-Whitney and chi 2-test, the level of significance p < or = 0.05. During the hospitalization we the patients were checked for symptoms of deep venous trombosis and tromboembolic or other adverse events. RESULTS: Hemoglobinemia and hematocrit in both groups significantly decreased after the operation (p < 0.0005), the differences between the studied and control groups were not significant. The number of administered blood units did not differ in the examined and control groups. The frequency of blood transfusions was postoperatively higher in the control group (59.1% as compared to 30%), however, the difference was not statistically significant (p = 0.059). Blood loss in the post-operative period was higher in the control group (p = 0.048). Patients from the control group got in total blood transfusion more frequently (p = 0.032). Differences in the total frequency of blood transfusion and in the amount of post operative blood loss were statistically significant. In the course of hospitalisation no signs of deep phlebothrombosis or thromboembolic condition were encountered in either group of patients. Complications were not recorded. DISCUSSION: Our results correspond with most of the published data. Blood loss of the operated on patients who were administered prior to and at the beginning of the operation in total 2.10(6) KIU of aprotinin (Antilysin Spofa) in infusion was on average by 33% less in the post-operative period and in the whole peropetive period they required less frequently blood transfusion (40% vs 73%). CONCLUSION: Infusion of aprotinin (Antilysin Spofa) in the dosage of the order of 106 KIU significantly reduces post-operative blood loss and frequency of transfusion in the peroperative period in patients undergoing THA. PMID- 11759475 TI - [Fractures of the sternum]. AB - PURPOSE OF THE STUDY: Assessment of the authors' group of patients with a fracture of sternum and comparison with available literary findings. MATERIAL AND METHODS: In a group of 188 patients with a blunt injury of chest who were hospitalised in the Faculty Hospital in Olomouc in the period of 1996-1999 there were 7 cases with the diagnosis of the fracture of sternum. In this group of patients we observed the cause of injury, occurrence of associated injuries, the potential of diagnostic methods, method of treatment and duration of hospitalization. RESULTS: Mostly they were patients with an isolated fracture of the sternum or with an associated injury requiring only a short-term hospitalization. One patient with a rupture of v. azygos died from the sequelae of other multiple injuries. Another patient sustained a fracture of sternum together with a massive hemothorax and hemomediastinum. On the basis of circulation stability this patient was treated conservatively. For details see the case report. Six patients were subsequently transferred to out-patient department and are now without complaints. DISCUSSION: The most beneficial examination for the diagnosis of the fracture of sternum remains lateral radiograph of the chest. With regard to potential injuries of mediastinal organs it is necessary to perform ap radiograph of the chest and ECG, in indicated cases also CT of the chest, angiography and echocardiography, if need be. In patients treated for a fracture of sternum the duration of hospitalization and mortality is determined by the severity of the associated injuries. Surgical treatment is considered rarely in fractures with a greater dislocation or in injuries or mediastinal organs. CONCLUSION: The incidence of the fracture of sternum has recently increased. Isolated injuries of the chest do not pose any diagnostic or therapeutic problem. Of much greater severity are associated injuries of lungs and mediastinal organs which require a precise diagnosis and careful observation of the patient. PMID- 11759476 TI - [A rare case of extensive bilateral polyethylene granuloma after knee replacement]. AB - The authors present a case of bilateral loosening of total knee arthroplasty as a result of polyethylene (PE) wear. Five and seven years after TKA the patient developed a polyethylene granuloma leading to extensive bone defects under the implant. Finally it resulted in pathological fracture of medial condyle of tibia. A revision PFC stabilized prosthesis was used for reimplantation. Bone defects were filled in by bone grafts from the bone bank. Authors point out the issues of PE wear. In the discussion they list various factors (time, indication, material, design and the factor of individual response of the organism) which may play an important role in the incidence of PE wear. The incidence of polyethylene granuloma in TKA is still a rare complication, however, it is necessary to take this issue into account as the number of such cases will undoubtedly grow. PMID- 11759477 TI - [Unusual dislocations of the carpal bones (case report)]. AB - The author describes 2 unusual injuries in the carpal region, i.e. the dislocation of os scaphoideum and os pisiforme. PMID- 11759479 TI - [The bone and joint decade 2000-2010. Traumatology of the locomotor system]. PMID- 11759478 TI - [Os scaphoideum--functional and clinical anatomy]. AB - 1. Scaphoid bone is the largest and clinically most significant bone in the proximal row of the carpal bones. It consists of three sections: proximal and distal pole and scaphoid waist. Extension and radial duction of the hand results in overloading of distal pole of scaphoid and its waist. 2. Nutrient arteries (from radial artery) enter the bone predominantly from the dorsal surface (75%). Functional intraosseous anastomoses do not exist. In 33% of cases proximal scaphoid has no separate nutrient arteries. 3. Scaphoid bone develops from two centres; however, two separate ossification nuclei are quite rare. Non-union of both centres during the early ontogenetic development results in os scaphoideum bipartitum congenitum. PMID- 11759480 TI - State systems for 'serious reportable events' will require reporting, analysis. PMID- 11759481 TI - NQF's list of 'serious reportable events'. PMID- 11759482 TI - JCAHO president calls for bioterror preparedness. PMID- 11759483 TI - Poor customer service has significant impact on bottom-line results. PMID- 11759484 TI - Hands across the hospital: handling internationals. PMID- 11759485 TI - Report sentinel events to managed care groups. AB - Must a sentinel event and root-cause analysis be reported to the MCO? PMID- 11759486 TI - [Training of neurosurgery residents]. AB - It is not a trivial matter to think about the topic of training neurosurgeons in Spain. To raise the question, I review the requirements in several countries. I comment on the process of selection, the length of training, the control of quality in the training program and the opportunities for clinical research in hospitals and in basic neurosciences. I express my opinion against a compulsory final exam. I propose that residents should inform the local or regional Health and Education Authorities about the dedication of staff members to training of postgraduate doctors and that this report should be taken into account and compensated economically in a proportional way to their efforts. PMID- 11759487 TI - [Research training in the programs of neurosurgery residency. Analysis of the situation in other developed countries and proposals to implementing the current program in Spain]. AB - Research performed by neurosurgeons has been always linked to the progress of our specialty, and research training is included in the Neurosurgery Residency Programs in developed countries. Since the methodology of research related to the basic knowledge of the nervous system function is becoming increasingly complex, it could be proposed that neurosurgeons can not longer contribute to productive research in neurosciences, and this idea might be easily accepted in certain countries such as Spain, where research training is not contemplated in the Residency Program of Neurosurgery. However, all neurosurgeons academic or not, should exhibit a critical and inquiring mentality which enables them to evaluate scientific information and communicate their own clinical experience to the neurosurgical community. Such a critical capacity can not be acquired by a resident trained only in the art of clinical diagnosis and the surgical technique. The new medical practice is based on both basic and clinical epidemiological research, and the new residents must be immersed into a motivating and inquisitive environment in which the scientific method is continuously applied to the clinical practice. In this paper I consider research training in Neurosurgery in developed countries with the aim of identifying a strategy for introducing a period devoted to research in the Spanish Residency Program. Thus, the methodologies, objectives, contents, duration and the moment for receiving research training in other countries are analysed and some alternatives for solving the problem in our country are pointed out. PMID- 11759488 TI - [Design, implementation, and results of the clinical pathway for herniated lumbar disk]. AB - INTRODUCTION: Clinical or critical pathways are a useful tool in the continuous quality improvement. They develop the main characteristics of the quality programs: implementation of the evidence based medicine, increase staff and patient satisfaction and adequacy in hospital costs. This is the application of evidence-based medicine to a process management and it promotes integration of clinical guides, protocols and algorithms. OBJECTIVE: We present our experience in the design, and first nine month's implementation and development of a clinical pathway for lumbar hemilaminectomy. PATIENTS AND METHODS: This clinical pathway consists on four documents: main guide and check sheet, preprinted treatment orders and variation sheet, iconographic information for the patients and patient satisfaction questionnaire. After desing, development and a pilot study, the hemilaminectomy critical pathway was permanently adopted by our Service. A total of 106 patients underwent programmed lumbar disc hemilaminectomy in our Service between April and December-1999. Patients' average age was 44.7 years (SD = 11.2), 55.3% were men and 43.7% women. Twelve were hospitalized in a ward other than Neurosurgery unit and therefore were excluded from the study. This evaluation is based on the initial results obtained from both the pathway documents and the general data collected as usual during hospital care. The impact of the critical pathway on hospital stay has been assessed by comparing the average stay of critical pathway patients to the average of the 70 hemilaminectomies performed at our Service in the period April-December 1998. RESULTS: Clinical pathway coverage has been 68% (standard > 80%). The patients' average stay was 4 days (SD = 1.1), one day more than planned. The pathway establishes a 4 day hospital stay (3 bed-days), a time that was fulfilled by 49% of the patients. The average stay of the 1998 patients was 5.6 days (SD = 2.7), 1.6 days more than the clinical pathway patients (p < 0.0001). Additionally, undesirable variability in the length of hospital stays was also reduced. Analysis of variations identified those corresponding to patient's condition, increases in medication beyond that originally specified due to patient needs, and unjustified prolonged stays. There were no systematic variations. There was a 2.2% incidence of adverse effects. Although satisfaction questionnaire was only returned by 51% of the patients (instead of > 70%), satisfaction index were 93% (vs 90%). CONCLUSIONS: Critical pathways are still under development and changing continuously. Nevertheless their impact on improving patient care and satisfaction, and resource consumption is already evident, and it constitutes a major aim to work in its complete development. PMID- 11759489 TI - [Quality analysis and evaluation of surgery for herniated lumbar disk. I. Methodology]. AB - A method for the analysis of the quality of the lumbar disc surgery was developed. The method assesses the important quality parameters such as scientific and technical quality (STQ), functional grades, quality of life, patients satisfaction and economic costs. The STQ related to the measurement of the care according to the available medical and technological knowledge was determined according to the performance of explicit criteria and standards in the clinic documentation (PEP method: Performance Evaluation Procedure). To measure the functional grade, a modification of Spanfort's criteria was used. To assess the quality of life a modification of 12-item Short Form health survey was applied. This form includes aspects like pain, social interaction, family characteristics, employment and psychological status. A questionnaire was used to measure satisfaction. The form was previously designed taking into account the patients and professionals criteria. In every stage care given, information issued, management and hosting, the patients and professionals opinions was considered and weighted. To calculate the cost three different systems were proposed i.e., Analytic economic management system (ABC-ABM), Weight related costs of DRGs (Diagnostic Related Groups) and Costs computed from price listing for consulting and hospitalization established by INSALUD. PMID- 11759490 TI - [Evaluation of the surgical process for herniated lumbar disk. II. Approximation to scientific-technical quality]. AB - INTRODUCTION: The procedure of surgical treatment of lumbar disc herniation belongs to the group of clinical practice procedures that have a great repercussion on health care systems. The high prevalence of this disease, the management variability and the possibility of improvement, explain the great interest in the evaluation of the quality of both treatment procedure and outcomes. OBJECTIVE: To determine and analyze the scientific and technical quality (STQ) of lumbar disc disease surgery and its correlation with some outcome measurements (clinical efficacy-functional grade and quality of life). METHODS: 172 patients who underwent a hemilaminectomy for lumbar herniated disc between 1996 and 1999 were studied. To analyze the STQ, we used the PEP (Performance Evaluation Procedure) method. A modification of Spangfort's criteria: to measure the functional grade- and the 12-item Short-form health survey (SF-12) to measure the quality of life- were the methods used to quantify outcomes, assessed after 12, 24 and 36 months after surgery. RESULTS: The mean overall STQ score was 0.83 (0-1). The anamnesis was the stage with worse information quality. Though neurosurgeons usually consider the anamnesis and physical examination data as the most important factors for decision making, these were no the best collected in the clinical reports. Surprisingly, data considered not relevant by neurosurgeons were registered with higher fidelity. An statistically significant correlation was found between STQ score and employment status among other parameters associated to the quality of life. The highest STQ scores were found in patients who did not return to work because of persistent pain 12 or 24 months after surgery (p < 0.02 and p < 0.04) and in patients showing poor social interaction and severe pain 12 months after surgery. When analyzing the completeness of clinical history data, statistically significant differences were observed in relation to the type of employment and the degree of physical effort needed at work. Patients working in positions without high skill requirements (p < 0.002) and involving a great physical effort (p < 0.05) had better registered data. Patients with better registered information tended to show a lesser clear surgical indication as a common characteristic, i.e., negative straight leg raising test, length of the current episode lasting more than 6 months and absence of symptoms (p < 0.01) for more than one year since the initial visit to the physician from the beginning of symptoms (p < 0.01), etc. CONCLUSIONS: This method established a significant correlation between STQ and clinical and presurgical variables, as well as between STQ and pain and activity after surgery. PMID- 11759491 TI - [Spinal epidural fibrosis following lumbar diskectomy and antiadhesion barrier]. AB - Although diskectomy after hemilaminectomy always produces some fibrosis, only few patients develop clinical symptoms. Fibrosis is one of the causes for failed lumbar disc surgery. Identification of fibrosis as the cause of recurring lumbar or sciatic pain requires the existence of a good clinical history and selective physical examination of the patient. MR is the imaging technique of choice although CT and myelography can be useful in some cases. Surgery can correct recurrent hernias, segmentary instability or spinal stenosis, but good results are less likely in patients with epidural fibrosis. When this exists, surgery should be directed to performing an arthrodesis of the vertebral space since the operation itself can destabilize the segment resulting in instability of the affected segment. Application of ADCON-L did not worse and in some cases improved the clinical condition of patients in double blind studies. Our multicentric double blind study showed no clinical differences among 253 patients at six months after surgery. Additionally, since this gel seems to avoid the development of fibrosis, it may prevent one of the main causes of failed disc surgery and, if reoperation is necessary due to disc remains or a lateral stenosis, the absence of fibrosis would facilitate surgery. PMID- 11759492 TI - [Posterior lumbar intersomatic fusion]. AB - Since late 1992 we started performing posterior lumbar interbody fusions together with pedicular screws and intertransverse fusion. Later on we decided to use posterior lumbar interbody fusions with titanium cages and autologous bone. We are presenting our results with a group of 52 patients with 6 months to 4 and a half years of follow-up. We have used the Prolo Functional Economic Outcome Rating Scale to evaluate our results, obtaining a high percentage (92%) of satisfactory results. The fusion's percentage was also very high, although we express the difficulty to evaluate the fusion grade considering the X-ray artifact produced by the cages. We conclude that PLIF with cages it is a surgical procedure with a high rate of success if we establish clearly the clinical criteria for its application and perform correctly the surgical technique. PMID- 11759493 TI - Drug resistant TB. PMID- 11759494 TI - Diagnostic issues in abdominal tuberculosis. AB - OBJECTIVE: To analyze the modes of presentation and diagnostic issues in the management of abdominal tuberculosis at a tertiary care hospital in a developing country, where most of the established diagnostic modalities are available. SETTING: The Aga Khan University Hospital, Karachi. METHODS: This study is a retrospective review of medical records of all inpatients, diagnosed to have abdominal tuberculosis, from January 1991 to December 1997. The data was collected and particularly analyzed for spectrum of presentation and role of various diagnostic modalities. Of special interest was the sub-group of patients, who after all investigations did not have a firm diagnosis. Following a literature review recommendations have been developed for empiric antituberculous therapy in such patients. RESULTS: A total of 135 patients were diagnosed to have abdominal tuberculosis with a mean age of 34 years and a male to female ratio of 1:2. Ninety-six (71%) patients presented with chronic abdominal symptoms, while 39 (29%) presented as an acute surgical emergency mandating exploratory laparotomy. A tissue-based diagnosis was established in 95 (70.30%) patients, while radiological diagnosis was made in 30 (22.2%) patients. In 10 (7.4%) patients all investigations undertaken could not reveal a final diagnosis; these were treated empirically on the basis of a strong clinical suspicion. CONCLUSION: The diagnosis of abdominal tuberculosis can be made confidently in most of the cases. There may be a small group of patients where diagnosis cannot be made despite appropriate investigations and a therapeutic trial of ATT may be considered with close monitoring according to a pre-fixed protocol. PMID- 11759495 TI - Conversion disorder: difficulties in diagnosis using DSM-IV/ICD-10. AB - OBJECTIVE: Conversion disorder presents differently in various cultures. The commonest symptoms in the Asian subcontinent may be very different from those seen in Western Hemisphere. This causes some difficulty in making a diagnosis while using DSM-IV and ICD-10. METHOD: This study searched inpatient records for the last 10 years at the Aga Khan University and collected some demographic data as well as assessed the phenomenology of conversion disorder in the patient population. RESULTS: We found unresponsiveness to be the most common symptom in this sample thus not exactly fitting the DSM-IV/ICD-10 picture. CONCLUSION: We observed that current criteria of conversion disorder as stated in two major classification systems are not totally relevant to the clinical practice in Pakistan and other parts of subcontinent. PMID- 11759496 TI - Pericardial effusion as a cause of morbidity in patients on maintenance hemodialysis: is it preventable? AB - OBJECTIVE: Cardiovascular diseases are the cause for 45% mortality and 20% morbidity in hemodialysis (HD) patients. Pericardial effusion (PE) accounts for 03-04% of all deaths in HD patients as a result of tamponade, arrhythmias or heart failure. This study aims to find out the prevailance and precipitating factors for PE in hemodialysis patients. PATIENTS AND METHODS: Fifty-five patients were identified for echo-cardiographic assessment on the basis of signs and symptoms suggestive of PE i.e., hypotension during dialysis, dyspnea, globular heart in chest x-ray, raised JVP, soft heart sounds and low voltage ECG. A matched controlled group of 55 patients for age, sex, dialysis schedule, cause of ESRD and dialysis bath, was also studied echocardiographically. RESULTS: Pericardial Effusion was detected in 12 patients (10.9%), 10 (83.3%) were on 2/week and only two on 3/week dialysis. Of these 75% were non-compliant in fluid intake and 58.3% were irregular in treatment. The morbidity of PE in study group (18.2%) is significantly higher as compared to controls (3.6%) (P = < 0.05). No correlation was found between development of PE and high iPTH and low albumin levels. Ten patients with mild PE responded to vigorous dialysis. Two patients developed cardiac tamponade needing pericardiocentesis. CONCLUSION: We have identified 2/week dialysis (inadequate dialysis dose), acetate bath and fluid and dialysis non-compliance as factors contributing to development of PE in HD patients. PMID- 11759497 TI - Behind the counter: pharmacies and dispensing patterns of pharmacy attendants in Karachi. AB - BACKGROUND: There is little literature available on dispensing patterns and unsupervised sale of medicines from pharmacies in developing countries. OBJECTIVE: This study obtained background information on pharmacies, assessed the level of training, knowledge and dispensing patterns of pharmacy attendants in Karachi. METHODOLOGY: This is a descriptive cross sectional study with convenient sampling. A structured questionnaire was used to interview pharmacy attendants. RESULTS: Of the 219 pharmacies surveyed, 62% reported more than 50 customers daily and 20% also sold items of general provision. Mean operating hours were 13. Only 24 (11%) had a visible license. On an average 3 attendants were employed per pharmacy. We interviewed one in each. Amongst the 219 interviewed, 77 (35%) were intermediate qualified and only 26 (12%) pharmacologically trained. Correct frequency of ORS administration was not known by 167 (76%) and 21% incorrectly suggested an anti-diarrhoeal preparation for viral diarrhoea in children. The knowledge of those with pharmacological training was significantly better. For respiratory tract infection in children approximately 60% did not know the correct dose of Paracetamol and Amoxicillin. Only 13 (6%) knew that Propanalol was contraindicated in hypertensive asthamatics. For Cotrimoxazole, metronidazole and lomotil only 40%, 21% and 15% respectively, were aware that these could not be dispensed without prescription. CONCLUSION: In the absence of trained pharmacists existing pharmacy attendants should be trained to improve drug dispensing patterns. PMID- 11759498 TI - Histological pattern of central nervous system neoplasms. AB - OBJECTIVE: To see in a large series of patients the histological pattern of CNS neoplasms and to provide a comprehensive data about the frequency of CNS neoplasms in Pakistani patients and to give a clearer idea about their prevalence. METHOD: Retrospective study of all consecutive cases of CNS neoplasms diagnosed at The Aga Khan University Hospital (AKUH) between 1st January, 1994 and 31st December, 1999. SETTING: The section of Histopathology, AKUH, Karachi. OBSERVATION: Our series included a large number of cases i.e., 1110. There are very few local studies on CNS tumours and none so large. Our data was correlated with published Western and Pakistani data. Glial tumours were the commonest primary CNS neoplasms followed by meningiomas. Among glial tumours, astrocytomas comprised the largest group and the majority were high grade (III and IV) astrocytomas. Percentages of anaplastic oligodendrogliomas and ependymomas were also significant. Male to female ratio was 1.6:1. However, meningiomas were more common in females. Almost half of the CNS tumours in patients 15 years or younger were in the posterior cranial fossa. Metastatic tumours were much lower as compared to the West. CONCLUSION: Except for the high percentages of anaplastic oligodendrogliomas and ependymomas and the low percentage of metastatic tumours, most of our findings roughly correspond with the published data. PMID- 11759499 TI - Endodermal sinus tumor of the vagina--a rare entity treated exclusively with chemotherapy. PMID- 11759500 TI - Congenital afibrinogenaemia in two families. PMID- 11759501 TI - Benign fibrous histiocytoma of the rib. PMID- 11759502 TI - Evaluation and management of urinary tract infection in children in general practice. PMID- 11759503 TI - Hepatitis E: review of a disease endemic in Pakistan. AB - Hepatitis E is enterically transmitted causing a self-limiting illness similar to hepatitis A. However, unlike hepatitis A, immunity to hepatitis E is not life long, hepatitis E is a disease of developing nations with improper sewage disposal and unclean water supplies. It is thought to be the most common cause of acute sporadic hepatitis in Pakistan, where it has also caused major epidemics. Hepatitis E causes a mild self-limiting illness with no long-term sequelae. However, it is especially severe in pregnant females in the second and third trimesters, in whom it results in a high mortality rate (up to 20%) and an increased incidence of stillbirths. Diagnosis depends on clinical findings and elevated hepatic enzymes. Protection from this disease in endemic areas lies mainly in prevention, as the vaccine for hepatitis E is still in the experimental stage. Provision of clean drinking water, hand washing before eating and proper disposal of sewage has been shown to decrease the incidence of this disease. PMID- 11759504 TI - Identifying the orientation of DNA fragment in recombinant plasmid by capillary electrophoresis with a non-gel sieving solution. AB - It was demonstrated that a capillary electrophoresis (CE) method with a non-gel sieving solution has been developed to identify the orientation of DNA fragments in recombinant plasmids in molecular biology. The influences of the concentration of sieving polymer HEC, the applied electric field strength and sampling on CE separation were analyzed concerning the optimization of separation. YO-PRO-1 was used as a DNA intercalating reagent to facilitate fluorescence detection. Under the chosen conditions (buffer, 1 x TBE containing 1 microM YO-PRO-1 and 1.2% HEC; applied electric field strength, 200 V/cm; electrokinetic sampling: time, 5 s; voltage, -6 kV), three DNA markers (phi 174/HaeIII, pBR322/HaeIII and lambda DNA/HindIII) were tested for further evaluating the relationship between the DNA size and the mobility. The established CE method conjugated with the enzymatic approach was successfully applied to identifying the DNA orientation of recombinant plasmid in transgene operations of a newly cloned gene from Arabidopsis Thaliana. PMID- 11759505 TI - Flow-injection chemiluminometric determination of some thioxanthene derivatives in pharmaceutical formulations and biological fluids using the [Ru(dipy)3(2+)] Ce(IV) system. AB - A flow-injection (FI) methodology using tris(2,2'-dipyridyl)ruthenium(II), [Ru(dipy)3(2+)], chemiluminescence (CL) was developed for the rapid and sensitive determination of three thioxanthene derivatives, namely zuclopenthixol hydrochloride, flupentixol hydrochloride and thiothixene. The method is based on the CL reaction of the studied thioxanthenes with [Ru(dipy)3(2+)] and Ce(IV) in a sulfuric acid medium. Under the optimum conditions, calibration graphs were obtained over the concentration ranges 0.002-6 migrograms/ml for zuclopenthixol hydrochloride, 0.5-15 micrograms/ml for flupentixol hydrochloride and 0.05-7.5 micrograms/ml for thiothixene. The limits of detection (s/n = 3) were 4.2 x 10( 9) mol/l zuclopenthixol hydrochloride, 2 x 10(-8) mol/l flupentixol hydrochloride and 4.5 x 10(-8) mol/l thiothixene. The method was successfully applied to the determination of these compounds in dosage forms and biological fluids. PMID- 11759506 TI - Guidance for selecting the measurement conditions in the dye-binding method for determining serum protein: theoretical analysis based on the chemical equilibrium of protein error. AB - A methodology for selecting the measurement conditions in the dye-binding method for determining serum protein has been studied by a theoretical calculation. This calculation was based on the fact that a protein error occurs because of a reaction between the side chains of a positively charged amino acid residue in a protein molecule and a dissociated dye anion. The calculated characteristics of this method are summarized as follows: (1) Although the reaction between the dye and the protein occurs up to about pH 12, a change in the color shade, called protein error, is observed only in a pH region restricted within narrow limits. (2) Although the apparent absorbance (the absorbance of the test solution measured against a reagent blank) is lower than the true absorbance indicated by the formed dye-protein complex, the apparent absorbance correlates with the true absorbance with a correlation coefficient of 1.0. (3) At a higher dye concentration, the calibration curve is more linear at a higher pH than at a lower pH. Most of these characteristics were similarly observed experimentally in the reactions of BPB, BCG and BCP with human and bovine albumins. It is concluded that in order to ensure the linearity of the calibration curve, the measurement should be performed at a higher dye concentration and sufficiently high pH where the detection sensitivity is satisfied. PMID- 11759507 TI - A nitrate-selective electrode based on tris(2,2',2" salicylideneimino)triethylamine. AB - A new nitrate-selective liquid-membrane electrode based on the tris(2,2',2" salicylideneimino)triethylamine-iron(III) complex has been developed. This electrode exhibits a linear Nernstian response over the range 10(-1)-10(-4) M of nitrate, with a slope of 54.3 +/- 0.9 mV per p[NO3]. The effects of the pH and the liquid-membrane composition were also investigated. The lifetime of the electrode is at least one month. The selectivity coefficients for ten monovalent ions were calculated. The preparation procedure of the electrode is very easy and inexpensive. Moreover, the proposed electrode was applied for the determination of nitrate in fertilizers. PMID- 11759508 TI - Evaluation and comparison of two selective extraction procedures for heavy metal speciation in sediments. AB - Two sequential extraction procedures (the former proposed by the Standard, Measurements and Testing-SM&T-program of European Union and the latter derived from those of Tessier and Forstner with various modifications) have been compared, by analyzing a reference material (CRM 601) certified for the content of heavy metals in the three solutions resulting from the SM&T procedure. Scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX) was used to evaluate the composition of the residues after various extractions. Reliable results, both in terms of precision and accuracy, were obtained for the first two steps of the SM&T scheme. As regards the third step, because it was modified during this work, a direct comparison of our results with those certified is not possible. SEM analysis confirmed that the scheme previously used in the laboratory was more aggressive compared to the SM&T procedure, which has also the advantage that the only CRM available for metal partitioning in sediments is certified using this method. PMID- 11759509 TI - Comprehensive-trace level determination of methyltin compounds in aqueous samples by cryogenic purge-and-trap gas chromatography with flame photometric detection. AB - A comprehensive method was developed for the sensitive and fast determination of trace levels of methyltin compounds in aqueous samples. Tin compounds in aqueous solution at pH 5 were converted to the corresponding volatile hydrides: CH3SnH3, (CH3)2SnH2, and (CH3)3SnH, by reaction with potassium borohydride. A CP-4010 purge and trap injector (PTI) was used to purge analyte species from water directly. The volatile derivatives were base-line separated on a capillary column in an Angilent-6890 gas chromatograph by a suitable temperature program and were detected by a flame photometric detector (FPD). The detection limits were 18 ng L 1 for monomethyltin, 12 ng L-1 for dimethyltin, and 3 ng L-1 for trimethyltin, respectively. This method was successfully applied to the determination of methyltin compounds in different aqueous samples. PMID- 11759510 TI - Highly sensitive determination method for total carbonate in water samples by flow injection analysis coupled with gas-diffusion separation. AB - A spectrophotometric method for the determination of total carbonate in water samples was developed. The method is based on the color change of an acid-base indicator in relation to the concentration of permeable gas substances through a membrane. By using a new portable FIA system equipped with a gas-diffusion unit, a highly sensitive and on-site determination of total carbonate in aqueous solutions was investigated. A new color-change system with 4-(2',4' dinitrophenylazo)-1-naphthol-5-sulfonic acid (DNN5S) was developed. Absorbance changes of the reagent solution were measured at 450 nm with a light-emitting diode (LED) as a light source. A new type of gas-diffusion unit was used, and was constructed with double tubing: the inner tubing was a micro porous PTFE (polytetrafluoroethylene) tubing (1.0 mm inner diameter and 1.8 mm outer diameter, pore size 2 microns, porosity 50%); the outer tubing was made of glass with 2.0 mm inner diameter. The optimized system conditions were as follows: the sample size was 200 microliters, the temperature of the air bath for the gas diffusion unit was 25 degrees C, and the length of the gas-diffusion unit was 15 cm; each flow rate was 0.3 ml min-1. For measuring carbonate at low concentrations, a method for preparing water with less carbonate was proposed: the carbonate content of the water was decreased down to 5 x 10(-7) M. The calibration graph was rectilinear from 1 x 10(-6) M to 10(-3) M, and the detection limit (corresponding to a signal-to-noise ratio of 3) was 1 x 10(-6) M of carbonate. The relative standard deviation (RSD) of ten measurements of 2.3 x 10(-5) M Na2CO3 solution was 1.9%. The total carbonate in various kinds of water (such as river, sea, rain, distilled and ultra purified) was determined. PMID- 11759511 TI - Extraction and separation of cationic surfactants from river sediments: application to a spectrophotometric determination of cationic surfactant in an aquatic environment using membrane filters. AB - The quantitative extraction of cationic surfactant (CS+) in river sediments was studied. Further, the developed method was applied to the spectrophotometric determination of CS+ in urban river sediment samples by solid-phase extraction with membranes. A mixture of methanol and hydrochloric acid was proposed as an eluent. Dried sediment was digested in the eluent under ultrasonic irradiation. After elution, the eluent was evaporated to almost dryness. The residue was dissolved in a small volume of methanol and diluted to a certain volume with water. The pH of the solution was adjusted to 4-5 to separate iron and some other metals as precipitates of hydroxides. The solution was passed through two-piled membranes: first glass-fiber and then polytetrafluoroethylene (PTFE) membranes. A small volume of methanol was passed through the membranes to elute any CS+ retaining on the membranes. After passing the methanol solution through a cationic exchange resin column, the retained CS+ was eluted with methanol containing a high concentration of sodium chloride. Water, Bromophenol Blue (BPB) and hydrochloric acid were added to the solution. The solution was passed through a mixed cellulose ester membrane filter to retain an ion associate of CS+.BPB-. The retained ion associate was dissolved in a small volume of N,N dimethylformamide together with the membrane filter, followed by the addition of triethanolamine to make the solution alkaline. The absorbance due to BPB2- was measured at 603 nm against a reagent blank. This method was applied to the determination of CS+ in river water and sediment. A cationic surfactant in sediments at 10(-5) mol kg-1 levels was detected with satisfactory precision. It was found that CS+ was about 500-fold enriched in the sediment from water at the place where domestic wastewater was discharged. PMID- 11759512 TI - Optimization of conditions for detailed compositional analysis of acrylic oligomers by supercritical fluid chromatography with temperature programming or modifier gradient technique. AB - Acrylic oligomers such as pentaerythritolacrylates (PEA), which are often utilized in the field of functionalized materials, generally consist of very complex homologous series. In this work, measuring conditions for packed-column supercritical fluid chromatographic separation of a complex PEA sample manufactured industrially were systematically examined using temperature programming or modifier gradient technique. Under the conditions thus optimized, not only the main components, PEA homologues containing different number of acryloyl groups, but also trace constituents such as their by-products formed through Michael addition reactions were favorably resolved on the resulting chromatograms. The fact that the coefficient of variation (CV) for relative intensity of each peak was approximately 3-6% even for the minor components suggested that detailed compositional analysis of PEAs could be performed precisely by the proposed method. PMID- 11759513 TI - Kinetically controlled separation of cadmium(II) from zinc(II) with dithizone in the presence of nitrilotriacetic acid. AB - The extraction rates of cadmium(II) and zinc(II) with dithizone (H2dz) in the presence of nitrilotriacetic acid (NTA) were measured, and the possible kinetic separation of cadmium(II) from zinc(II) was investigated. Upon the addition of NTA, the difference in the extraction rate between cadmium(II) and zinc(II) became large. Based on the observed rate constant under the condition [NTA] = 1 x 10(-2) mol dm-3, [H2dz]org = 1 x 10(-3) mol dm-3, and pH = 7.0, the shaking time required for the quantitative separation of cadmium(II) from zinc(II) was calculated to be between 326 and 995 s. The experimental results agreed with the prediction, and the quantitative separation of cadmium(II) from zinc(II) was performed within the above-mentioned range of shaking times. PMID- 11759514 TI - Solid phase extraction of ultra-trace amounts of Ag+ by using octadecyl silica membrane disks modified with a new fulvalen derivative. AB - A simple method for the rapid extraction and determination of ultra-trace amounts of Ag+ ions using octadecyl-bonded silica membrane disks modified with a recently synthesized fulvalen (tetramethyltetrathiafulvalen) (TMTTF) and graphite furnace atomic absorption spectrometry is presented. The extraction efficiency and influence of the flow rate, pH, nature of the counter ion and type and the least amount of eluent for the stripping of Ag+ from disks and breakthrough volume were evaluated. The maximum capacity of the membrane disks modified by 5 mg of TMTTF used was found to be 482 +/- 6 micrograms Ag+. The detection limit of the proposed method is 1.0 ng/dm3. The method was applied to the recovery of Ag+ ions from different synthetic and water samples. PMID- 11759515 TI - A facile spectrophotometric method for the determination of selenium. AB - A rapid and sensitive spectrophotometric method is described for the determination of trace amounts of selenium using Variamine Blue (VB) as a chromogenic reagent. The proposed method is based on the reaction of selenium with potassium iodide in an acidic medium to liberate iodine, which oxidizes Variamine Blue to form a violet-colored species having an absorption maximum at 546 nm. Beer's law is obeyed in the range 2-20 g of selenium in a final volume of 10 ml. The molar absorptivity and Sandell's sensitivity were found to be 2.6 x 10(4) l mol-1 cm-1 and 0.003 microgram cm-2, respectively. The optimum reaction conditions and other analytical parameters were evaluated. The effect of interfering ions on the determination is described. The proposed method has been successfully applied to the determination of selenium in real samples of water, soil, plant materials, human hair, and synthetic samples of cosmetics and pharmaceutical preparations. PMID- 11759516 TI - Direct spectrophotometric measurements of acid-catalyzed complexation of palladium(II) with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol at the heptane/water interface by a centrifugal liquid membrane method. AB - The centrifugal liquid membrane (CLM) method, designed for the rapid sample injection, was applied to the kinetic study of the complexation of palladium(II) with 2-(5-bromo-2-pyridylazo)-5-diethyaminophenol (5-Br-PADAP) in the heptane/water system. The formation rates of Pd(II)-5-Br-PADAP complex, which existed only at the heptane/water interface, could be directly measured by the CLM method combined with transmission spectrophotometry. We found that the formation rates of Pd(II)-5-Br-PADAP complex were accelerated by the protonation of 5-Br-PADAP at the diethylamino-group that did not coordinate to Pd(II) ion and that the rate constant for the reaction of protonated 5-Br-PADAP at the interface was close to that in the aqueous phase. The present study demonstrated that the CLM method was easily applicable for the measurements of relatively fast interfacial reactions. PMID- 11759517 TI - Rapid derivative spectrophotometric method for the determination of platinum in Pt-Ru/C catalyst using iodide media. AB - A rapid spectrophotometric method for the determination of platinum in 20% Pt-Ru (Pt:Ru (1:1)) carbon-supported catalyst has been developed. The samples of catalyst (0.85-12.60 mg) have been digested 1) in aqua regia after preliminary separation of carbon by burning or 2) directly in aqua regia in the presence of carbon. The detection of platinum was carried out in the obtained solutions after conversion of the metal into the iodide complex. The interfering effect of ruthenium on the detection of platinum was eliminated by the use of derivative spectrophotometry. Platinum was selectively determined by numerical calculation of the 4th-order-derivative absorption spectrum of the mixture of iodide complexes of both metals. PMID- 11759518 TI - Broadband vibrational sum frequency generation spectroscopy of a liquid surface. AB - An important advance in surface science has been the evolution of sum frequency generation to the application of studying surface structure and chemistry of liquid surfaces at the molecular-level by probing the vibrational signatures of surface molecules. Recently, broad-bandwidth sum frequency generation (BBSFG) spectroscopy has become an important tool for investigating gas-solid interfaces. BBSFG spectroscopy allows, theoretically, a surface sum frequency spectrum to be acquired within one pulse of the laser. In this paper, the viability of BBSFG to study inherently small nonlinear response interfaces and the time-resolving capability of this surface-selective technology are demonstrated. Presented here are the first published accounts of spectra from a liquid surface utilizing the broad-bandwidth sum frequency technology with acquisition times as low as 500 milliseconds. PMID- 11759519 TI - Fluorescent determination of noradrenaline and dopamine derivatized with Cy5 in capillary electrophoresis. PMID- 11759520 TI - Synthesis of a new color-developing reagent for the spectrophotometric determination of soaps on the basis of an ion-association reaction in aqueous solution. PMID- 11759521 TI - Indirect complexometric determination of mercury(II) using guanidine nitrate as a selective masking agent. PMID- 11759522 TI - Spectrofluorometric determination of erbium in seawater with 5,7-diiodoquinoline 8-ol and rhodamine 6G. PMID- 11759524 TI - Direct determination of vanadium in hair by graphite furnace atomic absorption spectrometry using air ashing in the graphite furnace. PMID- 11759523 TI - Flow-injection chemiluminescence determination of manganese(II) in natural water with solid sodium bismuthate as an oxidant. PMID- 11759525 TI - Crystal structure of an anthraquinone dye, C.I. disperse violet 27. PMID- 11759526 TI - Crystal structure of N,N,N',N'-Tetramethyl-1,4,10,13-tetraoxa-7,16 diazoniacyclooctadecane 1,5-naphthalenedisulfonate dihydrate. PMID- 11759527 TI - Crystal structure of a gadolinium(III) complex of tripodal tris(((5 chlorosalicylidene)amino)ethyl)amine. PMID- 11759529 TI - Crystal structure of 2,8,14-trimethyl-2,8,14-triazatetracyclo- [14(2,24),7,2(10,13)]tetracosa-4,6,10,12,16,18,19,21,23-nonaene-3,9,15-trione. PMID- 11759528 TI - Crystal structure of eta 5-pentamethylcyclopentadienyl-eta 6-toluene rhodium tetrafluoroborate, [Rh(Cp*)(eta 6-C6H5Me)](BF4)2 (Cp* = eta 5-C5Me5). PMID- 11759530 TI - [Surgical treatment of retinal complications of severe myopia]. PMID- 11759531 TI - [Paul Langerhans: from the cell to the islet]. PMID- 11759532 TI - [Semiology, etiology and pitfalls in acute abdominal pain]. AB - Acute abdominal pain is frequent and often distressing. This symptom must start a clinical investigation with mostly questioning and abdominal palpation for correct diagnosis and decision making. Half of the patients have either appendicitis or non-specific abdominal pain. PMID- 11759533 TI - [Imaging in acute abdominal syndromes]. AB - Imaging studies play an increasing role in patients with an acute abdomen. Guided by main symptoms, clinical findings and examination, imaging studies can confirm or change the diagnosis and the severity of the disease, guide the medical or surgical therapeutic. The plain film of the abdomen, despite its overall low sensibility and specificity, remains the current first-line radiological test in suspected bowel obstruction and detection of free air. The ultrasound and computed tomography, with a high sensibility and specificity, are more often used in first-line or after the plain film. PMID- 11759534 TI - [Appendicitis or non-specific pain in the right iliac fossa?]. AB - Nearly 300,000 appendectomies are performed yearly in France. The negative laparotomy rate for suspected acute appendicitis is about 20%. Appendiceal perforation increases the risk of postoperative complications and may lead to death. Differential diagnosis of right lower quadrant abdominal pain is a major public health problem. Reported means of increasing diagnostic accuracy have included in-hospital observation with clinical and biological structured data collection with or without computer-assisted diagnosis, ultrasonography, CT, and laparoscopy. The ideal diagnostic test is yet to be defined. However, structured clinical examination is the cornerstone of any management algorithm. "When in doubt, take it out" is no longer acceptable. PMID- 11759536 TI - [Acute abdominal pain of vascular origin]. AB - Pain of vascular origin generally reflects severe intestinal involvement and lesions that are rapidly irreversible. Diagnosis is difficult and treatment is often delayed. Such involvement should be considered systematically when confronted with any atypical abdominal pain, especially if it is intense and appears abruptly, in any patient with vascular disease or having cardiac rhythm disorder. At an early stage, the contrast between the severity of pain and the lack of general and physical signs should suggest emergency CT scan followed by GI arteriography for diagnosis and deciding treatment. If such measures are impossible, laparotomy should be performed. At the stage of infarct, the presence of an unstable haemodynamic condition and peritoneal signs require emergency laparotomy without paraclinical examinations. The severity of prognosis depends on the causes, the extent of lesions, patient background and the rapidity with which treatment is initiated. PMID- 11759535 TI - [Acute pelvic pain in women]. AB - Acute pelvic pains in women can reflect highly diverse disorders of varying severity, sometimes requiring surgery. It thus is clearly a part of abdominal emergencies in the adult. Good knowledge of underlying gynaecological disorders usually avoids unnecessary surgery. The use of echography has greatly contributed to reducing coelioscopy for diagnosis. PMID- 11759537 TI - [Acute abdominal pain in immunodepressed patients]. AB - Abdominal pain in immunodepressed patients is a challenge. Clinical presentation is often initially very vague and it is difficult to know if a patient needs early surgical exploration or not. Even in case of peritonitis, bowel function is normal in most of the patients, and signs of peritoneal irritation are minimal and frequently absent. Mortality and morbidity should decrease if diagnosis of peritonitis is made at an early stage. A high level of suspicion must be maintained when an immunodepressed patient presents with any abdominal pain. If pain persists, aggressive diagnostic efforts should be made, and early abdominal exploration should be considered. Laparoscopy has been demonstrated to be a secure and effective method for abdominal exploration and can be considered for diagnosis. Laparotomy should stay the procedure of choice when surgical treatment is needed in these critically ill patients. PMID- 11759538 TI - [Acute intestinal occlusions]. AB - Acute intestinal obstruction comprises a vast clinical entity characterized by the items of the obstruction syndrome. It encompasses numerous etiologies, and in Western countries adhesions are currently the main cause. The work up of this urgent surgical condition must above all be clinical, even though new techniques will probably improve their diagnosis and treatment (CT scan, stent). These new technologies still have to be documented and validated. Likewise, the laparoscopic approach of acute intestinal obstruction has to be prudent. The overall mortality of this urgent condition is still high, more than 10% of the patients. PMID- 11759539 TI - [Acute gastrointestinal hemorrhages]. AB - In patients with acute gastrointestinal bleeding, initial management includes emergency cares to restore or maintain circulatory stability, while the endoscopic examinations often determine the origin of bleeding. The most recent advances in this management concern early administration of proton pump inhibitors in bleeding ulcers, early administration of vasoactive drugs in patients with acute bleeding related to portal hypertension and the development of endoscopic therapy reducing the need for surgery. In all cases, an efficient collaboration between emergency physicians, gastroenterologist and surgeon is needed. PMID- 11759540 TI - ["Academic detailing"]. PMID- 11759541 TI - [Limited mouth opening. Diagnostic orientation]. PMID- 11759542 TI - [Hypertension in adults. Epidemiology, etiology, physiopathology, diagnosis, evolution, prognosis. Treatment of essential hypertension]. PMID- 11759543 TI - [Acute nasal-sinus and pharyngeal infections in children. Etiology, diagnosis, treatment]. PMID- 11759544 TI - [Acute nephritic syndrome. Physiopathology and diagnosis]. PMID- 11759545 TI - [Acute intestinal intussusception in infants. Physiopathology, diagnosis, emergency treatment]. PMID- 11759546 TI - Facilitators and barriers to adherence with home monitoring using electronic spirometry. AB - Adherence with prescribed therapies is a key factor in maintaining health in persons with chronic illnesses. The purpose of this descriptive study (which is one segment of a larger study being conducted to develop decision rules for early detection of infection or rejection in posttransplant patients) is to explore facilitators and barriers to adherence with home monitoring. Use of latent analysis revealed that the facilitators to adherence were health promotion, commitment to research, and following advice. Barriers to adherence were poor health status, laziness, and time conflict. Health professionals can use this information to plan strategies to promote adherence to home monitoring. PMID- 11759547 TI - Care before and after lung transplant and quality of life research. AB - Lung transplantation is a growing surgical option for patients with end-stage lung and pulmonary vascular diseases. After completing an extensive evaluation and meeting the selection criteria, patients are listed for either single or bilateral-sequential lung transplantation. Immediate postoperative management requires detailed attention to fluid management, monitoring for infection, reperfusion injury, pulmonary hygiene, and pain management. Length of stay depends on the patient's condition before transplant and postoperative complications. Discharge from the hospital can be as early as 7 days after transplantation. Newer immunosuppressive medications offer more options for treating and preventing rejection. Advanced practice nurses, such as coordinators, case managers, nurse practitioners, and clinical nurse specialists, are uniquely positioned to play key roles in coordinating the care of transplant patients across settings and both before and after the transplant procedure. The perioperative needs of lung transplant patients and the impact of this complex procedure on the recipients' and family's quality of life merit further investigation by clinicians and researchers. PMID- 11759548 TI - Breathing pattern retraining and exercise in persons with chronic obstructive pulmonary disease. AB - Breathing pattern retaining, in the form of pursed-lip breathing, has been used as one method in pulmonary rehabilitation to help alleviate the symptoms of dyspnea endured by people who suffer from airflow obstruction secondary to chronic obstructive pulmonary disease (COPD). Other techniques such as biofeedback also have been successfully used. This article describes the altered breathing patterns used by patients with COPD at rest and during physical activity. The literature is reviewed regarding techniques of breathing pattern retraining that have been developed to improve the capacity of persons with COPD to perform activities of daily living, a primarily rehabilitative outcome. PMID- 11759549 TI - Malnutrition in chronic obstructive pulmonary disease: adding insult to injury. AB - Weight loss in patients with chronic obstructive pulmonary disease has a negative effect on the clinical course of the patient. Causes of weight loss in this population are known to include the effects of an energy imbalance, increased cytokines, hypoxia, and glucocorticoid use. This article delineates mechanisms included in these processes and highlights specific deleterious aspects of each. In addition, the effects of the following therapies are discussed in light of recent research findings: nutrition support, anabolic steroids, recombinant human growth hormone, and polyunsaturated fatty acids. This review summarizes the current state of knowledge in this area. PMID- 11759550 TI - Chronic critically ill dyspneic patients: mechanisms and clinical measurement. AB - Dyspnea is a multidimensional, subjective perception of breathing difficulty commonly seen in patients who are critically or terminally ill. Understanding the mechanisms and assessment of dyspnea will help nurses in advanced practice roles to successfully manage these patients. Major mechanisms of dyspnea include stimulation of the chemoreceptors, stimulation of chest wall and intrapulmonary receptors, and increased sense of effort (also termed increased respiratory motor command). The causes of dyspnea are multifactorial, including numerous clinical conditions and aggravating situations that promote dyspnea. Assessment of dyspnea includes an accurate history of timing, precipitating factors, associated symptoms, alleviating factors, intensity and quality of the symptom. Measurement tools for dyspnea include both unidimensional and multidimensional tools, as well as tools that measure changes in the perception of dyspnea. Most tools have been tested for reliability and validity on healthy subjects or on patients with chronic obstructive pulmonary disease and, therefore, should be used with caution in critically or terminally ill patients. PMID- 11759551 TI - Airway pressure release ventilation: theory and practice. AB - Airway pressure release ventilation (APRV) is a relatively new mode of ventilation, that only became commercially available in the United States in the mid-1990s. Airway pressure release ventilation produces tidal ventilation using a method that differs from any other mode. It uses a release of airway pressure from an elevated baseline to simulate expiration. The elevated baseline facilitates oxygenation, and the timed releases aid in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, decreased sedation use, and near elimination of neuromuscular blockade. Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. Future research will probably support the use of APRV as the primary mode of choice for patients with acute lung injury. PMID- 11759552 TI - Communicating with mechanically ventilated patients: state of the science. AB - The literature clearly establishes the problems and difficulties of loss of speech among mechanically ventilated patients in the intensive care unit. Critical care nurses typically receive little or no training in the interpretation of nonvocal communication or in the assessment and application of augmentative communication methods. This article presents an integrative review of the research and related literature on communication with adult patients in critical care settings. Clinical issues and technological advancements in assistive and augmentative communication applicable to critical care are discussed and a new research agenda is proposed. PMID- 11759553 TI - Black, white, and shades of gray: common abnormalities in chest radiographs. AB - Chest radiographs remain one of the oldest, noninvasive methods for identifying chest diseases. This tool is relatively inexpensive, low risk, and important for the advanced practice nurse to use in making an initial differential diagnosis. Timely intervention depends on the advanced practice nurse's ability to recognize the radiographic abnormalities commonly associated with acute pulmonary disease. When linked with the history, presenting signs and symptoms, and a thorough physical assessment, the chest radiograph is key to appropriate diagnosis and management. This article reviews the basic radiographic lung densities, describes a systematic approach to ensure thorough chest radiographic interpretation, and presents characteristic chest radiographs found in the acute care setting. Selected examples of diffuse lung diseases, localized alveolar opacities, pleural effusions, and hyperlucency of the lungs will also be presented. PMID- 11759554 TI - Blunt chest trauma: review of selected pulmonary injuries focusing on pulmonary contusion. AB - Pulmonary injuries resulting from blunt chest trauma remain a common clinical entity for critical care and emergency nurses. In this article, the epidemiology and mechanism of injury most often observed in patients with blunt chest trauma are reviewed. Selected pulmonary injuries are discussed in terms of mechanism of injuries, assessment and diagnostic modalities, standard therapies, and cutting edge therapies used today with a focus on pulmonary contusion. Many advances and experimental therapies currently used in the management of the patient with severe lung injuries are discussed. A case study is presented highlighting a complicated case of a blunt chest injury resulting in severe pulmonary contusion. PMID- 11759555 TI - School-based management of the child with an acute asthma episode. AB - Asthma is a chronic inflammatory disorder of the airways that affects 5 million American children. In the past decade, asthma morbidity has dramatically increased. This increase is particularly apparent in poor minority inner-city children. School-based health centers offer a conveniently located setting for the acute treatment and long-term management of childhood asthma. Treatment of asthma using the most recent management guidelines offered in a school setting should result in a decrease in the morbidity and mortality associated with pediatric asthma. PMID- 11759556 TI - Inpatient care of the adult with an exacerbation of cystic fibrosis. AB - Patients with cystic fibrosis (CF) are living longer, albeit with chronic and progressive lung disease. Pulmonary exacerbations in CF are characterized by an increase in respiratory symptoms and a decrease in pulmonary function and gas exchange. Exacerbations that do not respond to outpatient management require hospitalization. Complications of CF can be devastating and life-threatening. Care of these patients is challenging not only because of the scope and severity of their medical problems, but also because of the need to coordinate services and to maintain continuity during transitions between hospital and home. PMID- 11759557 TI - Postoperative nosocomial pneumonia: nurse-sensitive interventions. AB - Nosocomial pneumonia (NP) is well documented as the second most common nosocomial infection. It is now more common in surgical patients than surgical-site or wound infection. Healthcare implications of NP include not only increased patient morbidity and mortality, but also increased use of healthcare resources. The advanced practice nurse plays an integral role in the prevention and minimization of NP across healthcare settings. This article focuses on postoperative NP after abdominal, cardiac, or thoracic surgery in the non-mechanically ventilated patient and discusses the diagnostic assessment, risk factors, and potential nurse-sensitive interventions to prevent or minimize this complication. Ideas for potential nursing research related to these risk factors are described. PMID- 11759558 TI - How settlement affects the legal process. PMID- 11759559 TI - The case for teaching history to student nurse anesthetists. PMID- 11759560 TI - 1% lidocaine injection, EMLA cream, or "numby stuff" for topical analgesia associated with peripheral intravenous cannulation. AB - The purpose of this study was to assess patient's perception of pain associated with peripheral intravenous (i.v.) cannulation, using 3 methods of applying local anesthetics. A prospective, randomized, quasi-experimental study was conducted, using a convenience sample of men and women, ASA physical status I, II, or III, undergoing outpatient or same-day surgery. Group 1 received a subcutaneous injection of 1% lidocaine, group 2 received topical EMLA cream for 45 to 60 minutes, and group 3 received treatment with "Numby Stuff" for 40 mA minutes. After the intended analgesic treatment was complete, the patient was asked to rate the pain experienced during the skin-numbing process. An i.v. was then started using an 18-gauge i.v. catheter, and the patient again was asked to rate the amount of pain experienced with the catheter insertion. A visual analog scale was used as the tool of measurement for pain. Results of the study showed that group 1 experienced a higher treatment pain score than either group 2 or group 3, while group 2 experienced a higher pain score when the i.v. was started than either group 1 or group 3. Of the 3 methods tested, results seem to indicate that the Numby Stuff system using iontophoresis is the superior method for decreasing the pain associated with peripheral i.v. cannulation, and application of the analgesic method does not cause significant pain. PMID- 11759561 TI - Transmyocardial laser revascularization. AB - In transmyocardial laser revascularization, a small left thoracotomy incision is made at the fifth rib. The surgeon dissects until adequate exposure of the heart is made, and the laser can be used. The areas to be lasered are identified, and treatment begins. As each laser beam penetrates the myocardium, a flash of bubbles can be seen on echocardiogram exiting the left ventricular outflow tract, which confirms adequate channeling. After revascularization, the mitral valve is inspected for any damage to papillary muscle or leaflets. This case report focuses on a new laser procedure that creates channels in the heart that promote angiogenesis and reestablish blood flow. A 47-year-old man presented for this surgery after having previous coronary artery bypass surgery. He had worsening angina and was not recommended for repeat bypass surgery because of his diffuse disease. Transmyocardial laser revascularization was offered as an alternative to medical therapy. Complications reported include dysrhythmia, bleeding, congestive heart failure, mitral valve damage, low cardiac output syndrome, and death. Many patients note substantial anginal relief after a few weeks. Transmyocardial laser revascularization gives an alternative to those with intractable angina and generally offers an improvement in quality of life. PMID- 11759562 TI - The impact of nalmefene on side effects due to intrathecal morphine at cesarean section. AB - Nalmefene is a long-acting opioid antagonist that provides long-term relief from side effects of intrathecal morphine sulfate. A randomized, double-blind, placebo controlled study was conducted to determine whether prophylactic nalmefene could decrease side effects of intrathecal morphine given during cesarean section, without affecting analgesia. Sixty parturients were given 0.25 mg of intrathecal morphine, 12.5 micrograms of fentanyl, and 11.25 to 15 mg of bupivacaine. A dose of 0.25 microgram/kg of nalmefene or placebo was given by intravenous piggyback immediately after delivery of the neonate. Nausea, vomiting, pruritus, and level of sedation were assessed for a 24-hour period using a 4-point ordinal scoring system. Pain was assessed by using a 0- to 10-point verbal analogue scale. A 5 point analgesic satisfaction survey also was completed. Subjects who received nalmefene required supplemental analgesia at a median of 6.00 hours after intrathecal morphine, compared with 14.12 hours in the placebo group (P = .037). No differences were found between the groups in the incidence of pruritus, nausea and vomiting, level of sedation, or analgesic satisfaction. We concluded that nalmefene at a dose of 0.25 microgram/kg does not decrease the incidence of side effects but increases the need for supplemental analgesics. PMID- 11759563 TI - Undisclosed port-wine stain--anesthetic implications and psychosocial considerations: a case report. AB - Port-wine stains (nevus flammeus, port-wine nevus) are congenital vascular lesions that have psychological and physiological implications for patient care. The location and size of these lesions can lead to complications related to anesthetic management. Facial lesions have the most profound psychological effect on the patient with respect to behavior alterations and reluctance to disclose the lesion's presence. Covering makeup has become increasingly effective not only in concealing the lesion, but also in being nearly undetectable during routine examination. Issues such as agent choice, surgical position, frequency of positioning evaluation, and choice of intravenous fluid should be considered when caring for a patient with a port-wine stain. In this case study the authors describe the anesthesia implications and outcome in a patient who refused to disclose her port-wine lesion in the preoperative interview and who ignored preoperative instructions to remove all makeup before presenting for surgery. PMID- 11759564 TI - Amputation and phantom limb pain: a pain-prevention model. AB - Within the figure of more than 200,000 surgical amputations performed in the United States each year lies another--70% of patients experience phantom limb pain after the procedure, and 50% still experience phantom pain 5 years after surgery. Patients describe burning, stabbing, twisting, cramping, or throbbing pains in the missing part. Adding to the patient's and the anesthesia professional's conundrum has been the lack of a simple model that tissue injury produces pain. The patient with a surgical amputation who experiences phantom limb pain can have several sources for discomfort including problems from the original tissue injury or from pathology, e.g., scarring or continued cellular dysfunction resulting from diabetes, ischemia, or infection. Suboptimal prosthesis fit and tissues and joints connected to the affected part can continue to generate pain long after surgical wound healing. In addition, nonaffected tissues and joints now made to carry extra loads as a result of altered gait and balance can sustain collateral stress and damage and produce nociception. In addition to this series of problems, amputee patients remain susceptible to the pain problems experienced by the general population. There is a positive correlation between a painful limb before amputation and experiencing chronic phantom limb pain. Authors have described patients with preamputation pain who benefited from effective preemptive analgesia and experienced less phantom limb pain. CRNAs can have a significant role in providing anesthesia and analgesia services to these patients and can begin to think in terms of preventing lifelong pain. PMID- 11759565 TI - Assessing pain responses during general anesthesia. AB - Major technical and pharmacological achievements in recent years have greatly influenced the practice of anesthesia. Clinical signs related to the main aspects of anesthesia, i.e., hypnosis, analgesia, and muscular relaxation, are increasingly obtainable from variables supplied by the monitoring equipment. It is not known, however, to what extent more indirect, patient-associated clinical signs of pain/depth of anesthesia are still considered of importance and relied on in the intraoperative management of surgical patients. The aims of the present study were to assess what clinical signs, indirect as well as monitor-derived, are considered indicative of intraoperative pain or depth of anesthesia by nurse anesthetists during general anesthesia. In connection with anesthetic management of surgical patients, Swedish nurse anesthetists (N = 40) were interviewed about clinical signs that they routinely assessed and were asked if the observed signs were considered indicative mainly of intraoperative pain or depth of anesthesia. It was found that skin-associated responses (temperature, color, moisture/stickiness) were commonly considered to indicate intraoperative pain rather than depth of anesthesia. Respiratory movements, eye reactions, and circulatory responses were considered to be indicative of either pain or insufficient depth of anesthesia. The present data indicate that indirect physiological signs are still considered of major importance by anesthesia nurses during the anesthetic management of surgical patients. PMID- 11759566 TI - Preemptive analgesia applied to postoperative pain management. AB - Acute postoperative pain can cause detrimental effects on multiple organ systems. To treat pain effectively, a thorough knowledge of the anatomy and physiology of pain and its transmission is necessary. Painful stimuli, like that produced by a surgical incision, can lead to a hyperexcitable state in the spinal cord. This hyperexcitable state can exacerbate postoperative pain. Once the hyperexcitable state has been established, a larger dose of analgesic drug is needed than if hyperexcitability had been prevented. When an analgesic is administered before the bombardment of painful stimuli that occurs with surgical incision, postoperative pain can be greatly diminished. Epidural, intravenous, and intramuscular opioids have been shown to reduce the severity of postoperative pain to a greater extent when administered before surgical stimuli rather than following it. PMID- 11759567 TI - Review of effects of water pollution on the breeding success of waterbirds, with particular reference to ardeids in Hong Kong. AB - Predatory waterbirds, such as ardeids, are susceptible to bioaccumulation of pollutants through the ingestion of contaminated food sources. High body burdens of contaminants, including PCBs, PAHs, cadmium, mercury, lead, copper, zinc and arsenic have been detected in many bird species worldwide. There is a paucity of literature, however, linking contaminant body burden and effects on reproductive success in waterbirds. This review is a synthesis of pertinent literature on this topic, with specific reference to contaminant residues in various tissue types, relationship between body burden and reproductive success, and the use of biomarkers to predict more serious adverse affects. The impetus for this review was the development of a conservation strategy and management plan (commissioned by the Agriculture, Fisheries and Conservation Department of Hong Kong Special Administrative Region (SAR)) for an important wetland in Hong Kong that supports many threatened waterbirds, including ardeids. PMID- 11759568 TI - Enchytraeids and microbes in Zn polluted soil: no link between organism-level stress responses and ecosystem functioning. AB - We studied the presence of zinc tolerance in enchytraeid worm (Cognettia sphagnetorum, Oligochaeta) from a metal-polluted forest soil in The Netherlands. In a dose response experiment, we compared Zn sensitivity, measured as body growth and reproduction, of these enchytraeids with that of animals taken from three unpolluted sites. Because C. sphagnetorum is a keystone species, regulating microbial processes in coniferous forest soil, we performed a microcosm experiment to study the interaction of enchytraeids from several sites with soil microbes. The idea was to study whether there is a link between metal stress response of individuals (tolerance level, life history alteration) and changes observed at higher organization levels of the biological system (trophic interaction and decomposition processes). We did not find evidence for increased metal tolerance of C. sphagnetorum. Worms from the polluted site actually had reduced body growth, indicating negative fitness effects caused by long-lasting metal stress. The density and biomass of the worm population from the polluted site was low in Zn contaminated soil. Presence of enchytraeids enhanced and Zn contamination reduced the activity of microbes in the soil. Enchytraeids from different sites with different life histories and population development, however, had the same effect on microbes. Hence, observed stress responses of individuals and populations could not be linked to density-dependent trophic interactions and ecosystem functioning in the soil-decomposer food chain. PMID- 11759569 TI - Single and combined effects of sediment-associated PAHs on three species of freshwater macroinvertebrates. AB - Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants of sediments. Sediment quality criteria often use toxicity data for individual PAHs. However, PAHs always occur in field sediments as a complex mixture of compounds. In this study, the toxicity of phenanthrene (P), fluoranthene (FLA) and benzo(k) fluoranthene (B), alone or in combination, was assessed using monospecific sediment tests of acute toxicity (between 24 h and 14 days). The test sediments were spiked formulated sediments. Toxicity of PAHs was determined on a freshwater pelagic organism, Daphnia magna, on an epibenthic organism, Hyalella azteca, and on a benthic organism, Chironomus riparius. The phototoxicity of fluoranthene and phenanthrene was verified. Benzo(k)fluoranthene was not phototoxic and presented no toxicity for the three organisms tested up to 300 mg/kg, concentration rarely found in the environment. For all PAHs, the toxicity towards Daphnia magna was two-fold higher in the sediment toxicity tests than in the water-only standard tests, probably due to suspended contaminated particles and contact of daphnids with sediment. For phenanthrene, the LC50s found were 50, 15 and 20 mg/kg dry weight sediment, respectively for Daphnia magna, Hyalella azteca and Chironomus riparius. The bioassays on fluoranthene yielded LC50s of 10, 5 and 15 mg/kg dw respectively for Daphnia magna, Hyalella azteca and Chironomus riparius. LC50s of the PAHs mixture (1/3 of each compound by weight) were around 10 mg/kg dry weight sediment for Hyalella azteca and 20 mg/kg for Chironomus riparius. The effects of PAHs in the mixture seemed to be synergistic. This study gives new data about PAH toxicity and showed that the additivity of PAH effects could be inadequate to assess the environmental risk. PMID- 11759571 TI - Magnetic resonance imaging observation of the conus medullaris. AB - We examined the anatomical height and shape of the conus medullaris in 602 cases using magnetic resonance imaging. The peak of the distribution of the conus height was at the middle one-third of L1. The comparison of the conus level had no significant relationships with age or sex, but the juvenile group had more a caudal distribution of the conus level. The shape of the conus medullaris was classified into three types, and the type B was most frequently observed. PMID- 11759570 TI - Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part III: Cyproterone acetate and vinclozolin as antiandrogens. AB - The effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed in laboratory experiments. In this last of three publications, the responses of the fresh water snail Marisa cornuarietis and of two marine prosobranchs (Nucella lapillus, Nassarius (Hinia) reticulatus) to the antiandrogenic model compounds cyproterone acetate (CPA) and vinclozolin (VZ) are presented. The snails were exposed to nominal CPA concentrations of 1.25 mg/L alone and simultaneously to a potent synthetic estrogen (ethinylestradiol), androgen (methyltestosterone) or an indirectly acting xeno-androgen (tributyltin) in experiments with adult specimens and in a life cycle test for 12 months. Marisa and Nucella were furthermore exposed to nominal concentrations of 0.03-1.0 microgram VZ/L for up to 5 months. The antiandrogens induced a number of biological responses in all three species. The length of the penis and of accessory male sex organs (e.g., penis sheath, prostate) were significantly reduced. For Marisa, this effect occurred only in sexually immature specimens and was reversible as the males attained puberty. Typical androgen-mediated responses (imposex development, delayed spermatogenesis, tubulus necrosis of the testis with orchitis and Leydig cell hyperplasia) were partially or totally suppressed by a simultaneous administration of CPA. In the two marine species even adult, sexually mature males responded to antiandrogens with a reduction of the male sex organs and an advancement of the sexual repose phase. The results for CPA and VZ are compared with the effects of an exposure to xeno-estrogens (bisphenol A, octylphenol) and xeno-androgens (triphenyltin, tributyltin) in the same species. Each group of endocrine disruptors induces a characteristic set of toxicological effects in prosobranch snails which can be used as endpoints in an organismic invertebrate test for the identification of endocrine mimetic test compounds. Estrogens cause primarily an induction of superfemales resulting in an increased female mortality by the enhancement of spawning mass and egg production. The main effects of androgens are a virilization of females by imposex development and a marked decrease of the fecundity. Compared with estrogens and androgens, the antiandrogen responses seem to be less drastic and might have--in contrast to the two other disruptor classes--no biologically significant effects at the population level. PMID- 11759572 TI - Surgical technique and functional results of irreparable cuff tears reconstructed with the long head of the biceps tendon. AB - The purpose of the study was to evaluate the results obtained from patients who were treated with open surgical technique using the long head of the biceps tendon for irreparable tears of the rotator cuff tendons. Between May 1992 and January 1997, 14 patients underwent rotator cuff reconstruction of irreparable tears at our clinic. These patients were evaluated before and after a minimum follow-up of 26 months (mean: 40.2 months) following surgery with the Constant's functional score. The long heads of the biceps tendons were found to be hypertrophied in all 14 shoulders and in 10 of them they were also subluxated. After re-seating the surgically enlarged biceps tendon onto the center of the uncovered head region, the biceps tendon to cuff tendon repair and the biceps tenodesis were done in all shoulders. The mean functional Constant's score before surgery was 46.7 points (poor) and the mean postoperative score at the final follow-up was 75.35 points (good). Satisfactory results were achieved in 85.7% of the patients. These results suggest that this surgical technique can be used to attain a painless and functional shoulder after irreparable cuff tear reconstruction. PMID- 11759573 TI - Exercise intensity based on heart rate while walking in spastic cerebral palsy. AB - We examined the heart rate (HR) of subjects with spastic cerebral palsy (CP) in order to estimate exercise intensity while walking. The subjects were 17 subjects with CP (14.0 +/- 3.7 years of age) containing 7 subjects rated as level 1, 4 subjects rated as level 2, and 6 subjects rated as level 3 by the Gross Motor Function Classification System, and 7 normal subjects (12.4 +/- 2.8 years of age) were used as a controls. Even in subjects whose gross motor function was excellent (rated as level 1), the HR significantly increased while walking when compared to normal subjects (p < 0.05), although the walking speed between the groups was not different. According to the HR, the exercise intensity while walking was adapted from weakly to moderately and thought to be appropriate for exercise. On the other hand, walking speed was significantly reduced in the subjects rated as level 2 and 3 (p < 0.05), and the HR increased significantly (p < 0.05). Seven of the ten subjects rated as either level 2 or 3 showed a high HR of over 150 beats/min while walking. The HR while walking of the two subjects rated as level 3 continued to increase although the walking speed was kept constant. The walking exercise would be too strong and become detrimental to such subjects. PMID- 11759574 TI - The relationship between postoperative ligament balance and preoperative varus deformity in total knee arthroplasty. AB - We hypothesize that in knees with severe varus deformities, varus-valgus ligament imbalance tends to remain postoperatively after total knee arthroplasty. The purpose of this study was to evaluate the correlation between preoperative varus deformity and postoperative ligament balance quantitatively measured by stress radiograph using Telos SE in total knee arthroplasty. In this study, 44 knee arthroplasties in 32 patients were evaluated. We defined the angle in varus and valgus stress as "varus angle" and "valgus angle," and the sum of varus angle and valgus angle as "sum of varus-valgus angle." There was a significant correlation between preoperative lateral femoral angle and varus angle (p < 0.0001, r = 0.56), which means that postoperative ligament imbalance tends to remain in knees with preoperative varus deformities. There was a significant correlation between the postoperative period and the sum of varus-valgus angle, which suggests that knees with total knee arthroplasty have potential to increase laxity postoperatively. PMID- 11759575 TI - Orthopaedic manifestations of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown origin. It affects multiple organ systems, but most frequently the musculoskeletal system. Highly variable manifestations include small and large joint involvement, spinal involvement, periarticular tissue symptoms, and complications associated with chronic steroid use such as osteonecrosis, osteoporosis, and stress fractures. The following review summarizes the common orthopaedic manifestations of SLE. PMID- 11759576 TI - Subtrochanteric fractures. A review of treatment options. AB - Subtrochanteric fractures of the femur were originally grouped with comminuted intertrochanteric fractures. However, they pose their own distinct management problems mainly due to biomechanical differences in stability and are now considered separately. There are several classification systems but the most widely accepted is the one proposed by Seinsheimer in 1978. Many different methods have been employed in the management of this group of fractures with varying rates of success. The management has altered as new implants have been developed to try to overcome the shortfalls of the existing implants. This study is a review of the literature and was carried out using Medline and the Cochrane Library to look at the management methods employed in the past and today. Most of the published articles are retrospective uncontrolled reports of the results of management and it is difficult to suggest management principles from them. The other main shortcoming is that, although there are several devices available on the market for the management of these fractures, most of the literature concerns one or two of them. The results reported examine union rates and failure of implants leading to reoperation. This is a crude outcome measure, and there is very little in the literature regarding patient function. In order to provide evidence-based advice on the best management options for these difficult fractures, future studies should be designed as randomized controlled trials and place more emphasis on studying patients' outcomes. PMID- 11759577 TI - Osteoid osteoma in the base of the coracoid process of the scapula. Excision by anterior approach: a case report. AB - Osteoid osteoma in the base of the coracoid process of the scapula is very rare and diagnosis and treatment often is delayed. A lesion in this atypical location may seem surgically unreachable. This report is of a case of osteoid osteoma in the base of coracoid process in a 14-year-old female. The lesion had been diagnosed as a nontumorous condition and overlooked for four years. Computed tomography and magnetic resonance imaging revealed a nidus in the base of the coracoid process. The en bloc excision of the osteoid osteoma was managed by an anterior approach using an osteotomy of the coracoid process. A 12-month follow up examination revealed no symptoms and computed tomography showed bone healing with no recurrence of the tumor. PMID- 11759578 TI - Hydroxyapatite-coated total hip replacements in patients 65 years of age and over. AB - Prospective review examined 69 patients aged over 65 years (mean: 73 years; range: 65 to 85 years) who underwent 72 primary hydroxyapatite-coated total hip replacements by one surgeon. The femoral component used was titanium alloy coated by hydroxyapatite on the proximal third and the acetabular component was spherical and unthreaded, coated with hydroxyapatite. All patients were evaluated clinically by Harris Hip Score and radiologically using Engh's criteria with a mean follow-up of 86 months (range: 29 months to 10 years). Preoperative radiologic evaluation for osteoporotic bone using the Singh index was performed. Average Harris Hip Score increased from 45 before surgery to 89 at last follow up. Two femoral and one-acetabular components were shown to probably be loose, but none was definitely loose or unstable by Engh's criteria. There was no correlation between clinical and radiologic results with respect to age, sex, and preoperative diagnosis. In contrast, significant statistical correlation was demonstrated between Charnley groups A or B, and group C, with regard to the Harris Hip Score (p = 0.047). There was no correlation between Charnley groups and radiological results. There was no statistical difference between patients with osteoporotic bone (Singh 1-3) and non-osteoporotic bone (Singh 4-6) with respect to clinical and radiologic evaluation. These early clinical and radiologic results compare favorably with those of hydroxyapatite-coated total hip replacements for younger patients and cemented total hip replacements in older patients. We recommended that hydroxyapatite-coated total hip replacements should not be reserved for younger patients. They can be used safely in patients over 65 years of age, promising minimal postoperative thigh pain and satisfactory clinical and radiologic results. PMID- 11759580 TI - Better killing through chemistry. PMID- 11759579 TI - Failure of a four-hole Medoff Sliding Plate. A case report. PMID- 11759581 TI - Evaluating the threat. PMID- 11759582 TI - Reseizing the controls. PMID- 11759583 TI - Stem cell showstopper? PMID- 11759584 TI - Vessels of death or life. PMID- 11759585 TI - Photonic crystals: semiconductors of light. PMID- 11759586 TI - The first stars in the universe. PMID- 11759587 TI - India, Pakistan and the bomb. PMID- 11759589 TI - Long-distance robots. PMID- 11759588 TI - The origins of personal computing. PMID- 11759590 TI - [Waiting for results of the studies. Bacterial toxin against migraine?]. PMID- 11759591 TI - [Sauna improves endothelial function. Let patients with heart diseases sweat?]. PMID- 11759592 TI - [Treatment recommendations in sinusitis. To cure the sinuses--but causally!]. PMID- 11759593 TI - [Diets in irritable bowel syndrome--what do they really achieve? Please no culinary sadism!]. PMID- 11759594 TI - [Deep stimulation helps in advanced Parkinson's disease. Electrodes in the brain spare L-dopa]. PMID- 11759595 TI - [Adults tired of vaccines. Ask your patients about vaccine protection!]. AB - In general, vaccinations can be divided into standard and indication-related vaccinations. The former, which are mandatory for adults too, include tetanus and diphtheria, and those against influenza and pneumococci in people older than 60. The term indication vaccinations is used to describe those that are recommended in certain situations, for example, in the presence of a particular occupational risk, in certain underlying diseases, or particular situations, e.g. women of childbearing age, people living in regions endemic for meningoencephalitis, and drug addicts. Since the vaccination rate in the case of adults leaves much to be desired, all physicians should be required to ensure that "gaps" are closed and immunization protection is maintained. PMID- 11759596 TI - [Your most important duty concerning vaccinations in childhood. Instruct the parents!]. PMID- 11759597 TI - [Influenza, pneumococci, tetanus: the most important vaccinations in old age]. AB - In comparison with younger patients, the elderly are at an appreciably higher risk of contracting an infectious disease. Such infections can be prevented or ameliorated by appropriate vaccination, in particular in the case of pneumococcal pneumonia, influenza and tetanus. Older individuals may have an attenuated response to immunization, presumably because of inadequate thymus gland function and the weakening of cell-mediated immunity and, secondarily, of the humoral immune response to antigens. Studies have shown that the immunization rate among the elderly in Germany is inadequate; this applies in particular to the high-risk population living in nursing homes. Campaigns aimed at increasing awareness of the need for immunization are therefore urgently required. PMID- 11759598 TI - [The patient has chronic pain. Is the family physician to be blamed, too?]. PMID- 11759600 TI - [For many years has chronic obstructive lung disease, then: suddenly unconscious]. PMID- 11759599 TI - [Emergencies in the practice. Unclear exanthema: when does danger threaten?]. PMID- 11759601 TI - [Cox-2 inhibitors in the focus. Rofecoxib as effective as the "classics"]. PMID- 11759602 TI - [BDI plans "general and family medicine". "Light" internist as better family physician]. PMID- 11759603 TI - [Photodynamic therapy. To see well into old age]. PMID- 11759604 TI - [The study shows: PDT prevents long-term vision loss]. PMID- 11759605 TI - [Erection dysfunction can reveal diabetes. Penis as "divining rod of the vascular system"]. PMID- 11759606 TI - [Calcium antagonists lower not only blood pressure. Arteriosclerosis is braked too]. PMID- 11759607 TI - [Side effects cause enormous costs. Expensive arthritis therapy]. PMID- 11759608 TI - [Infarct prevention for diabetics. To lower blood sugar is not enough]. PMID- 11759609 TI - [Osmotically active laxative. Fast aid in chronic constipation]. PMID- 11759610 TI - [Step-children of pain therapy. The newborn suffer particularly severely]. PMID- 11759611 TI - "Unruffling" the mystique of therapeutic touch. PMID- 11759612 TI - Investigating therapeutic touch. PMID- 11759613 TI - Community-acquired pneumonia in adults. AB - The incidence and mortality rates of community-acquired pneumonia (CAP) continue to rise as patients age. The clinical presentation of CAP is variable; therefore, diagnosis can be challenging. Clinicians must rely on a careful history and physical examination when choosing empirical antibiotic treatment. Using current guidelines, this article discusses the pathogenesis, clinical presentation, differential diagnosis, prognosis, and treatment of adults with CAP in the primary care setting. PMID- 11759614 TI - Screening for cognitive impairment in the older adult. AB - Screening for cognitive impairment in the older adult is an often overlooked element of health promotion. Health care providers may assume that existing deficits will be apparent on routine medical encounters. Frequently, however, patients who are functionally impaired can present a convincing facade of normalcy. Objective screening is necessary to recognize decline. This article briefly reviews normal age-related changes in cognition and suggested screening tools as well as differential diagnoses, highlighting reversible aspects of impairment. Additionally, potential corrective measures are considered where appropriate. This evaluation will become even more significant as the geriatric population steadily increases. PMID- 11759615 TI - Professional considerations for providing mifepristone-induced abortion. AB - Primary care clinicians who provide comprehensive reproductive heath care can now offer patients mifepristone (Mifeprex) as an abortifacient option. Clinicians, however, must first determine if the state in which they practice has regulations specifying who can perform abortions and dispense drugs, and they must consider clinical office zoning ordinances, staffing, public relations issues, and reimbursement. This article discusses the pharmacology of mifepristone and misoprostol, professional considerations, and how to prevent and manage adverse effects and complications of medical abortion. PMID- 11759616 TI - Acute signs and symptoms require prompt follow-up. PMID- 11759617 TI - [Atrial fibrillation. Epidemiology and physiopathology]. PMID- 11759618 TI - [Guidelines for antithrombotic therapy in atrial fibrillation: what the Italian Hemostasis and Thrombosis Society thinks]. PMID- 11759619 TI - [Thromboembolism in non-rheumatic atrial fibrillation]. PMID- 11759620 TI - Reimbursement options for WOC(ET) nurses in ambulatory care. PMID- 11759621 TI - Services for patients with mental retardation. PMID- 11759622 TI - Hot tub folliculitis. PMID- 11759623 TI - Oral versus IV steroids for asthma. PMID- 11759624 TI - Reimbursement options for WOC(ET) nurses in home health care. PMID- 11759625 TI - Assisting with rapid sequence intubation. PMID- 11759626 TI - Quick mental status charting. PMID- 11759627 TI - An expensive cast cover. PMID- 11759628 TI - Good bandages for the elderly. PMID- 11759629 TI - Pediatric tips. PMID- 11759630 TI - Violence in the emergency department. PMID- 11759631 TI - From the Centers for Disease Control and Prevention. Outbreak of pneumococcal pneumonia among unvaccinated residents of a nursing home--New Jersey, April 2001. PMID- 11759632 TI - From the Centers for Disease Control and Prevention. Self-reported asthma prevalence among adults--United States, 2000. PMID- 11759633 TI - JAMA patient page. Teenaged drivers. PMID- 11759634 TI - Mountaineers among Croatian physicians. PMID- 11759635 TI - Summaries for patients. Outcomes of chronic infection with hepatitis B virus. PMID- 11759636 TI - Summaries for patients. Is aspirin a cost-effective addition to colorectal cancer screening? PMID- 11759637 TI - Summaries for patients. Genes and HIV progression. PMID- 11759638 TI - Summaries for patients. Effects of universal vaccination for hepatitis B. PMID- 11759639 TI - Why I do what I do. PMID- 11759640 TI - Obituary. Patrick David Wall, 1925-2001. PMID- 11759641 TI - Ketamine as a street drug. AB - The excellent safety profile of ketamine has made it the drug of choice for both pediatric sedation and much veterinary medicine. Fortunately, this safety record also means that few patients who deliberately overdose during recreational use will have substantial morbidity or mortality. Most morbidity and mortality will occur from accidents during the induced dysphoric state. Since vomiting occurs with high doses, aspiration is a distinct possibility in the deeply comatose patient. PMID- 11759642 TI - Guiding principles for research involving animals and human beings. PMID- 11759643 TI - Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. AB - BACKGROUND: The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy. METHODS: We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment. RESULTS: The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion. CONCLUSIONS: Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone. PMID- 11759644 TI - Fluconazole prophylaxis against fungal colonization and infection in preterm infants. AB - BACKGROUND: Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely low-birth-weight infants. METHODS: We conducted a prospective, randomized, double blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients. RESULTS: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented. CONCLUSIONS: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g. PMID- 11759645 TI - A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. AB - BACKGROUND: Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure. METHODS: A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours. RESULTS: Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure; 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001). Treatment with valsartan also resulted in significant improvements in NYHA class, ejection fraction, signs and symptoms of heart failure, and quality of life as compared with placebo (P<0.01). In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme (ACE) inhibitors or beta-blockers, valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs. CONCLUSIONS: Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy. However, the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concern about the potential safety of this specific combination. PMID- 11759646 TI - Images in clinical medicine. Renal-cell carcinoma extending into the vena cava and right side of the heart. PMID- 11759647 TI - Clinical practice. Lowering cardiac risk in noncardiac surgery. PMID- 11759648 TI - Mesenteric venous thrombosis. PMID- 11759649 TI - Aldosterone in congestive heart failure. PMID- 11759650 TI - Removing the primary tumor after the cancer has spread. PMID- 11759651 TI - Will parity in coverage result in better mental health care? PMID- 11759652 TI - Ovarian cancer, oral contraceptives, and BRCA mutations. PMID- 11759653 TI - Ovarian cancer, oral contraceptives, and BRCA mutations. PMID- 11759654 TI - Autoimmune diseases. PMID- 11759655 TI - The coxibs, selective inhibitors of cyclooxygenase-2. PMID- 11759656 TI - The coxibs, selective inhibitors of cyclooxygenase-2. PMID- 11759657 TI - The coxibs, selective inhibitors of cyclooxygenase-2. PMID- 11759658 TI - Medical mystery--the answer. PMID- 11759659 TI - Web sites and misinformation about illicit drugs. PMID- 11759661 TI - Images in clinical medicine. Liver abscess due to Eikenella corrodens from a fishbone. PMID- 11759660 TI - Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. PMID- 11759662 TI - Summaries for patients. Postmenopausal estrogen helps prevent atherosclerosis in some women. PMID- 11759663 TI - Summaries for patients. Predictors of outcomes in patients with HIV infection treated with indinavir, zidovudine, and lamivudine. PMID- 11759664 TI - Summaries for patients. Weight-training exercises to counteract the negative effects of low-protein diets in people with kidney disease. PMID- 11759665 TI - Summaries for patients. Blood flow to the heart varies during the menstrual cycle in premenopausal women with heart disease. PMID- 11759666 TI - Commentary: What is a teacher? PMID- 11759667 TI - From the Centers for Disease Control and Prevention. Investigation of bioterrorism-related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. PMID- 11759668 TI - From the Centers for Disease Control and Prevention. Updated recommendations for antimicrobial prophylaxis among asymptomatic pregnant women after exposure to Bacillus anthracis. PMID- 11759669 TI - From the Centers for Disease Control and Prevention. Interim recommendations for protecting workers from exposure to Bacillus anthracis in work sites in which mail is handled or processed. PMID- 11759670 TI - Antioxidants and zinc to prevent progression of age-related macular degeneration. PMID- 11759671 TI - JAMA patient page. Nursing homes. PMID- 11759672 TI - Unusual enzymes involved in five pathways of glutamate fermentation. AB - Anaerobic bacteria from the orders Clostridiales and Fusobacteriales are able to ferment glutamate by at least five different pathways, most of which contain enzymes with radicals in their catalytic pathways. The first two pathways proceed to ammonia, acetate and pyruvate via the coenzyme B12-dependent glutamate mutase, which catalyses the re-arrangement of the linear carbon skeleton to that of the branched-chain amino acid (2S,3S)-3-methylaspartate. Pyruvate then disproportionates either to CO2 and butyrate or to CO2, acetate and propionate. In the third pathway, glutamate again is converted to ammonia, CO2, acetate and butyrate. The key intermediate is (R)-2-hydroxyglutaryl-CoA, which is dehydrated to glutaconyl-CoA, followed by decarboxylation to crotonyl-CoA. The unusual dehydratase, containing an iron-sulfur cluster, is activated by an ATP-dependent one-electron reduction. The remaining two pathways require more then one organism for the complete catabolism of glutamate to short chain fatty acids. Decarboxylation of glutamate leads to 4-aminobutyrate, which is fermented by a second organism via the fourth pathway to acetate and butyrate, again mediated by an unusual dehydratase which catalyses the reversible dehydration of 4 hydroxybutyryl-CoA to crotonyl-CoA. The fifth pathway is the only one without decarboxylation, since the gamma-carboxylate of glutamate is reduced to the amino group of delta-aminovalerate, which then is fermented to acetate, propionate and valerate. The pathway involves the oxidative dehydration of 5-hydroxyvaleryl-CoA to 2,4-pentadienoyl-CoA followed by reduction to 3-pentenoyl-CoA and isomerisation to 2-pentenoyl-CoA. PMID- 11759673 TI - Introduction of specialty functions by the position-specific incorporation of nonnatural amino acids into proteins through four-base codon/anticodon pairs. AB - Position-specific incorporation of nonnatural amino acids into proteins (nonnatural mutagenesis) via an in vitro protein synthesizing system was applied to incorporate a variety of amino acids carrying specialty side groups. A list of nonnatural amino acids thus far successfully incorporated through in vitro translation systems is presented. The position of nonnatural amino acid incorporation was directed by four-base codon/anticodon pairs such as CGGG/CCCG and AGGU/ACCU. The four-base codon strategy was more efficient than the amber codon strategy and could incorporate multiple nonnatural amino acids into single proteins. This multiple mutagenesis will find wide applications, especially in building paths of electron transfer on proteins. The extension of translation systems by the introduction of nonnatural amino acids, four-base codon/anticodon pairs, orthogonal tRNAs, and artificial aminoacyl tRNA synthetases, is a promising approach towards the creation of "synthetic microorganisms" with specialty functions. PMID- 11759674 TI - Antimicrobial properties of Allium sativum (garlic). AB - Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties. PMID- 11759675 TI - Photobioreactors: production systems for phototrophic microorganisms. AB - Microalgae have a large biotechnological potential for producing valuable substances for the feed, food, cosmetics and pharmacy industries as well as for biotechnological processes. The design of the technical and technological basis for photobioreactors is the most important issue for economic success in the field of phototrophic biotechnology. For future applications, open pond systems for large-scale production seem to have a lower innovative potential than closed systems. For high-value products in particular, closed systems of photobioreactors seem to be the more promising field for technical developments despite very different approaches in design. PMID- 11759676 TI - Perspectives in the biological function, the technical and therapeutic application of bone morphogenetic proteins. AB - The bone morphogenetic proteins (BMPs) belong to the transforming growth factor beta superfamily of growth and differentiation factors and have been characterized by their ability to induce new bone formation in ectopic (non skeletal) sites. BMPs are secreted molecules and are key regulators in early embryogenesis and organogenesis. One of the many functions of BMPs is to induce cartilage, bone, and connective tissue formation in vertebrates. This osteo inductive capacity of BMPs has long been considered very promising for applications in bone repair, in the treatment of skeletal diseases, and in oral applications such as dentiogenesis and cementogenesis during regeneration of periodontal wounds. We discuss here biological roles of the BMPs in the organism and their signaling cascades leading to bone and cartilage formation in particular. It is also the aim of this review to evaluate the potential and the problems of BMPs in skeletal tissue engineering for the regeneration of bone damaged by disease or trauma and to serve as therapeutic agents for periodontal defects. PMID- 11759677 TI - Biotransformation of benzaldehyde into (R)-phenylacetylcarbinol by filamentous fungi or their extracts. AB - Extracts of 14 filamentous fungi were examined regarding their potential for production of (R)-phenylacetylcarbinol [(R)-PAC], which is the chiral precursor in the manufacture of the pharmaceuticals ephedrine and pseudoephedrine. Benzaldehyde and pyruvate were transformed at a scale of 1.2 ml into PAC by cell free extracts of all selected strains, covering the broad taxonomic spectrum of Ascomycota, Zygomycota and Basidiomycota. Highest final PAC concentrations were obtained with the extracts of Rhizopus javanicus and Fusarium sp. [78-84 mM (11.7 12.6 g/l) PAC within 20 h from initial substrate concentrations of 100 mM benzaldehyde and 150 mM pyruvate]. (R)-PAC was in about 90-93% enantiomeric excess. Rhizopus javanicus had the advantage of faster growth than Fusarium sp. Rhizopus javanicus mycelia were used as an example in a biotransformation process based on whole cells and benzaldehyde and glucose as substrates. The substrate pyruvate was generated through the fungal fermentation of glucose. Only 19 mM PAC (2.9 g/l) were produced within 8 h from 80 mM benzaldehyde. with evidence of significant benzyl alcohol production. PMID- 11759678 TI - A perfusion-cell bleeding culture strategy for enhancing the productivity of eicosapentaenoic acid by Nitzschia laevis. AB - A perfusion-cell bleeding culture strategy was developed for enhancing the productivity of eicosapentaenoic acid (EPA) by the diatom Nitzschia laevis. As the strategy combined the concepts of continuous culture and perfusion culture, it allowed continuously and simultaneously harvesting the algal cells and removing inhibitory compounds during the cultivation. Compared with a single operation of continuous culture, the perfusion-cell bleeding culture greatly enhanced the steady-state biomass concentration, biomass productivity, EPA yield, EPA productivity and glucose utilization efficiency. The perfusion-cell bleeding culture also allowed higher biomass productivity and EPA productivity than the single perfusion culture did. At a bleeding rate of 0.67 day(-1) and a perfusion rate of 0.6 day(-1), the EPA productivity achieved 175 mg l(-1) day(-1), which is the highest ever reported in microalgal cultures. PMID- 11759679 TI - Zymomonas mobilis CP4 fed-batch fermentations of glucose-fructose mixtures to ethanol and sorbitol. AB - Zymomonas mobilis CP4 fed-batch fermentations of glucose-fructose mixtures were carried out at different operational conditions (aeration, feed rate and substrate concentration) to test their effects on the system productivity. In these fermentations, the main products were ethanol and sorbitol. Kinetic parameters were calculated using the experimental data. However, parameters in the sorbitol synthesis rate were estimated from data recorded in different experiments in order to avoid the effect of the simultaneous cell growth and ethanol synthesis. In this case, the crude cell extract was used as source of the enzyme responsible for the sorbitol synthesis. The highest degree of conversion of fructose into sorbitol obtained with the extract was equal to 71% in a sugar mixture with an initial concentration of 200 g/l. Results obtained in the fed batch fermentations showed that aeration of the culture has a positive effect on the final biomass concentration. However, final ethanol concentration is lower under aerated conditions. The best sugar yields to biomass and ethanol were 0.032 and 0.411 g/g, respectively. On the other hand, the highest sorbitol yield in the fed-batch fermentations was 0.148 g/g. PMID- 11759680 TI - Highly efficient Aerococcus viridans L-alpha-glycerophosphate oxidase production in the presence of H2O2-decomposing agent: purification and kinetic characterization. AB - Glycerophosphate oxidase was purified from Aerococcus viridans cells by phase partitioning in Triton X-114, ammonium sulfate fractionation, FPLC ion-exchange chromatography and FPLC hydrophobic-interaction chromatography. The purification achieved from a crude extract of A. viridans was 38-fold with a 32% recovery of activity. Under the growth conditions used, A. viridans strain CECT 978 proved to be an excellent glycerophosphate-oxidase producer, with enzyme production 2,800 fold greater than that described in the literature for the same microorganism. The culture medium used in the present work is that commonly used for cultivation of this microorganism, except that an H2O2-decomposing enzyme was added. The addition of catalase to the growth medium had a clear effect on the growth rate. Furthermore, methylglyoxal, a metabolite that is formed enzymatically from triose phosphates, was found to be an inactivator of glycerophosphate oxidase activity. PMID- 11759681 TI - Shrimp chitin as substrate for fungal chitin deacetylase. AB - The fungal chitin deacetylases (CDA) studied so far are able to perform heterogeneous enzymatic deacetylation on their solid substrate, but only to a limited extent. Kinetic data show that about 5-10% of the N-acetyl glucosamine residues are deacetylated rapidly. Thereafter enzymatic deacetylation is slow. In this study, chitin was exposed to various physical and chemical conditions such as heating, sonicating, grinding, derivatization and interaction with saccharides and presented as a substrate to the CDA of the fungus Absidia coerulea. None of these treatments of the substrate resulted in a more efficient enzymatic deacetylation. Dissolution of chitin in specific solvents followed by fast precipitation by changing the composition of the solvent was not successful either in making microparticles that would be more accessible to the enzyme. However, by treating chitin in this way, a decrystallized chitin with a very small particle size called superfine (SF) chitin could be obtained. This SF chitin, pretreated with 18% formic acid, appeared to be a good substrate for fungal deacetylase. This was confirmed both by enzyme-dependent deacetylation measured by acetate production as well as by isolation and assay for the degree of deacetylation (DD). In this way chitin (10% DD) was deacetylated by the enzyme into chitosan with DD of 90%. The formic acid treatment reduced the molecular weight of the polymeric chain from 2x10(5) in chitin to 1.2 x 10(4) in the chitosan product. It is concluded that nearly complete enzymatic deacetylation has been demonstrated for low-molecular chitin. PMID- 11759682 TI - Optimal design for the maximization of Penicillium cyclopium lipase production. AB - Penicillium cyclopium triacylglycerol lipase production was maximized in stationary batch culture. We used a surface response methodology based on a Doehlert experimental design to study the effect on the lipase activity released in the culture medium of the three most important factors: substrate concentration, pH and inoculum. Besides reducing the number of experiments required for optimization, this technique allowed us to quantify the lipase activity in any part of the experimental domain.We determined an optimal set of conditions for high lipase production: 1% substrate (corn steep), pH 5.5 and an inoculum of 10(4) spores/ml. Between conditions giving the minimum and the maximum lipase production, we observed a nine-fold increase of both the predicted and measured values. PMID- 11759683 TI - Influence of carbon source on alpha-amylase production by Aspergillus oryzae. AB - The influence of the carbon source on alpha-amylase production by Aspergillus oryzae was quantified in carbon-limited chemostat cultures. The following carbon sources were investigated: maltose, maltodextrin (different chain lengths), glucose, fructose, galactose, sucrose, glycerol, mannitol and acetate. A. oryzae did not grow on galactose as the sole carbon source, but galactose was co metabolized together with glucose. Relative to that on low glucose concentration (below 10 mg/l), productivity was found to be higher during growth on maltose and maltodextrins, whereas it was lower during growth on sucrose, fructose, glycerol, mannitol and acetate. During growth on acetate there was no production of alpha amylase, whereas addition of small amounts of glucose resulted in alpha-amylase production. A possible induction by alpha-methyl-D-glucoside during growth on glucose was also investigated, but this compound was not found to be a better inducer of a-amylase production than glucose. The results strongly indicate that besides acting as a repressor via the CreA protein, glucose acts as an inducer. PMID- 11759684 TI - Cloning and characterization of the gene cahB encoding a cephalosporin C acetylhydrolase from Acremonium chrysogenum. AB - An important problem during the production of cephalosporin C by Acremonium chrysogenum is the hydrolysis of cephalosporin C to deacetylcephalosporin C, since the latter compound has no commercial value and represents an unwanted side product. Characterization of the enzymatic process that gives rise to deacetylcephalosporin C will help to avoid the accumulation of this side-product. An extracellular cephalosporin C acetylhydrolase (CPC-AH) from Acremonium chrysogenum C10 was purified to near homogeneity. This enzyme had a molecular mass of 31 kDa, a pl of 4.0, and showed relatively little affinity for cephalosporin C (Km 33.7 mM). We sequenced twenty amino acids at the amino terminal end; a probe based on this sequence was then used to clone the cephalosporin acetylhydrolase (cahB) gene. cahB encodes a pre-protein of 383 amino acids with a deduced molecular mass of 38,228 Da. The sequenced 20 amino acids of the purified protein corresponded to amino acids 107-127 deduced from the cahB gene, suggesting that mature CPC-AH results from processing of the pre protein after Gln-106. cahB is located on chromosome VIII of A. chrysogenum C10 and is not linked to the cephalosporin early or late gene clusters. It is expressed as a single 1.4-kb transcript after 72 h of cultivation. Expression declined in batch cultures after 120 h even though CPC-AH activity was observed until 144 h. The CPC-AH protein resembles other wide-spectrum substrate fungal esterases that are functionally related to serine proteases. The cahB gene does not seem to be related to the cephalosporin biosynthesis genes and encodes an esterase active on several substrates in addition to cephalosporin C. PMID- 11759685 TI - Physiological characterisation of Penicillium chrysogenum strains expressing the expandase gene from Streptomyces clavuligerus during batch cultivations. Growth and adipoyl-7-aminodeacetoxycephalosporanic acid production. AB - The production of adipoyl-7-aminodeacetoxy-cephalosporanic acid (ad-7-ADCA) was studied, using two recombinant strains of Penicillium chrysogenum carrying the expandase gene from Streptomyces clavuligerus. The adipoyl-side chain of this compound may easily be removed using an amidase; and this process therefore represents a new route for the production of 7-ADCA, which serves as a precursor for the production of many semi-synthetic cephalosporins. In this study, one low- and one high-yielding strains were characterised and the specific productivities of ad-7-ADCA and byproducts of the biosynthetic pathway were compared. The fluxes through the biosynthetic pathway were quantified and it was found that there was a 30% higher flux through the expandase in the high-yielding strain. In both strains, there was a significant degradation of adipate. Furthermore, the initial adipate concentration in batch cultures was shown to have a positive effect on the formation of ad-7-ADCA. PMID- 11759686 TI - Replacement of arginine-171 and aspartate-453 in Streptomyces coelicolor malate synthase A by site-directed mutagenesis inactivates the enzyme. AB - Malate synthase, a key enzyme of the glyoxylate cycle, catalyzes the condensation of glyoxylate and acetyl-CoA to yield malate and CoA. Escherichia coli is known to possess two forms of malate synthase, A and G respectively. The recent elucidation of the E. coli malate synthase G crystal structure suggested two residues, Arg338 and Asp631, are essential for catalysis. Multiple sequence alignment of 26 known malate synthase enzymes revealed that the two proposed sites are highly conserved, despite the low homologies between the two distinct forms of the enzyme (13-18%). The conservation of these residues in both forms of malate synthase suggests that they possess a similar catalytic strategy. Thus, despite the absence of a three-dimensional structure for malate synthase A, the significance of this enzyme in the primary metabolic pathway has prompted the investigation of the involvement of the corresponding residues, Arg171 and Asp453, in Streptomyces coelicolor malate synthase A by site-directed mutagenesis. Heterologous expression in E. coli followed by purification of the constructed mutant proteins, Arg171Leu and Asp453Ala, were performed and subsequent enzyme assays of the purified mutant proteins indicated a significant loss of catalytic activity, thus attesting to the need for the corresponding conserved residues to maintain malate synthase functionality. PMID- 11759687 TI - Activation of plasma membrane H+-ATPase by ammonium ions in Aspergillus niger. AB - The addition of ammonium ions to Aspergillus niger cells originally growing on another nitrogen source resulted in rapid medium acidification. The addition of glucose or other fermentable sugars to the mycelium growing on glycerol did not have the same effect. The enzyme responsible for acidification seems to be plasma membrane H+-ATPase, which is most probably triggered by phosphorylation. Using specific activators and inhibitors, we tried to figure out which signalling pathway is involved in the process. No activation of H+-ATPase could be detected in the presence of diacylglycerol and other activators of protein kinase C, indicating that the stimulus is transmitted by another signalling chain. In the presence of inhibitors known to suppress the phosphatidyl-inositol signalling pathway, such as neomycin, compound 48/80 and calmidazolium, no increased H+ ATPase activity could be detected after the addition of ammonium ions. However, some tested inhibitors of the cAMP signalling pathway could not prevent activation of the enzyme by the stimulant. These results support the model in which ammonium-induced activation of proton extrusion in A. niger is mediated via the phosphatidyl-inositol signalling pathway, involving Ca2+/calmoduline dependent protein kinase but not protein kinase C. PMID- 11759688 TI - Effect of high-cell-density fermentation of Candida utilis on kinetic parameters and the shift to respiro-fermentative metabolism. AB - Candida utilis NRRLY-900 was grown in a high-cell-density continuous culture without oxygen limitation. Glucose or molasses was used as carbon source at 30 g l(-1) or 100 g (reducing sugars) l(-1). At 30 g glucose l(-1), the dilution rate (D) immediately before the change in respiratory metabolism (Dr) was approximately 0.40 h(-1). At this value of D, the corresponding culture in molasses did not reach the Dr value. When the reducing sugar concentration in the feed was 100 g l(-1), the Dr was 0.15 h(-1) for glucose and 0.3 h(-1) for molasses. When D>Dr, accumulation of ethanol and organic acids occurred, due to physiological changes in C. utilis. The changes observed were a decrease in the biomass yield coefficient per gram of oxygen consumed (YO2) and a sudden increase in the specific oxygen consumption rate (qO2) for each substrate. Therefore, at growth rates above Dr in a high-cell-density culture, C. utilis acquired a flexible catabolism directed towards alternative fermentation routes. The D at which metabolic changes took place seemed to depend on the nature and concentration of the carbon source. Biomass productivity was higher with molasses than with glucose when the fermenter was operated at high D values. PMID- 11759689 TI - Metabolic profiles and aprE expression in anaerobic cultures of Bacillus subtilis using nitrate as terminal electron acceptor. AB - Cultures using nitrate as the terminal electron acceptor were conducted in Schaeffer's medium to evaluate the growth performance and metabolic profiles of Bacillus subtilis, and its potential to express the aprE (subtilisin) gene under anoxic conditions. Nitrate was converted to ammonia through nitrite reduction; and different product profiles were observed during the growth phase when nitrate was added at various concentrations (4-24 mM) to Schaeffer's medium containing glucose (4 g l(-1)). If nitrate was not limiting, then acetic acid and acetoin were accumulated, suggesting a limitation of reduced cofactors but, if nitrate became limiting, then lactic acid and butanediol were accumulated, suggesting an excess of reduced cofactors. Due to a strong lysis at the onset of the end of the growth phase, sporulation frequency and aprE expression were negligible in anaerobic batch cultures. Fed-batch fermentation allowed the development of a stationary phase through a continuous supply of glucose and nitrate. In this case, sporulation frequency was almost null, but interestingly aprE expression was similar to that found in aerobic cultures. PMID- 11759690 TI - Selection of Mycobacterium sp. strains with capacity to biotransform high concentrations of beta-sitosterol. AB - In this work, phytosterol-biotransforming strains were selected from Mycobacterium sp., using a high concentration of beta-sitosterol. The selection was made by culturing the strains in a medium enriched with 14 g beta sitosterol/l as the unique source of carbon. During 2 months, the bacterial cultures were transferred successively. The extraction of the biotransformation products was made with methanol and ethyl acetate. The qualitative and quantitative analysis was made by means of thin-layer chromatography, gas-liquid chromatography (GLC) and GLC-mass spectrometry. Under these conditions, it was observed that after seven transfers, the strains MYcobacterium sp. MB-3683 and the Mycobacterium fortuitum B-11045 increased their biotransformation capacity from 20% to 64% and from 34% to 55%, respectively. The products in the highest proportion identified for each trial were androstenedione and androstadienedione. The results suggest that the high substrate concentration could be a selective mechanism to obtain strains more efficient in the biotransformation of beta sitosterol into steroidal bases. PMID- 11759691 TI - Formation of glucoside conjugates during biotransformation of dibenzofuran by Penicillium canescens SBUG-M 1139. AB - Penicillium canescens oxidises dibenzofuran (DBF) to produce monohydroxylated derivatives and other more hydrophilic metabolites. These substances are water soluble but unstable in organic solvents such as ethyl acetate, acetone or dichloromethane. Both extraction with ethyl acetate and enzymatic treatment of the aqueous culture filtrate with beta-glucuronidase led to decay of the hydrophilic metabolites and indicated these products to be glycoside conjugates. The glycosyl residue was identified as glucose both by liquid chromatography and by the use of glucose oxidase. The conjugate pattern formed was the same in type and amount, independent of the carbon source used for cultivation of the fungus. Clearly, DBF transformation in P canescens occurred in two phases: first the conversion to 2-, 3-, and 4-hydroxydibenzofuran (phase I), followed by the formation of the corresponding glucosyl conjugates (phase II). In contrast, 2,3 dihydroxydibenzofuran added to the cultures was transformed by ring cleavage producing a muconic acid-like dead-end product. PMID- 11759692 TI - Characterisation of extracellular polysaccharides produced by Crypthecodinium cohnii. AB - The valuable polyunsaturated fatty acid, docosahexaenoic acid, can be produced by cultivation of the heterotrophic microalga, Crypthecodinium cohnii. During batch growth of C. cohnii on glucose, sea salt and yeast extract for 5 days, so far unreported extracellular polysaccharides were produced. These caused an increased viscosity and a strong drop in the maximum oxygen transfer. The viscosity increased most markedly as cells entered the stationary phase. The polysaccharides varied in size (from 6 kDa to >1,660 kDa) and monomer distribution. A high molecular mass fraction (from 100 kDa to >1,660 kDa) and a medium molecular mass fraction (6-48 kDa) were prepared. The high molecular mass fraction contained (on a molar basis) 71.7% glucose, 13.1% galactose and 3.8% mannose, whereas the medium molecular mass fraction contained 37.7% glucose, 19.8% galactose and 28.1% mannose. Other monomers present in both fractions were fucose, uronic acid and xylose. Monomers were coupled mainly via alpha-(1-3) links. Increased viscosity due to polysaccharide production complicates the development of commercial, high cell-density processes for the production of docosahexaenoic acid. PMID- 11759693 TI - New method for exopolysaccharide determination in culture broth using stirred ultrafiltration cells. AB - A new method to remove simple carbohydrates from culture broth prior to the quantification of exopolysaccharides (EPS) was developed and validated for the EPS-producing strain, Lactobacillus rhamnosus RW-9595M. This method uses ultrafiltration (UF) in stirred cells followed by polysaccharide detection in the retentate by the phenol-sulfuric acid method. The UF method was compared with a conventional method based on ethanol extraction, dialysis, protein removal by trichloroacetic acid (TCA) and freeze-drying. EPS production during pH-controlled batch fermentations in basal minimum medium, whey permeate (WP). and whey permeate supplemented with yeast extract, minerals and Tween-80 (SWP) was determined by the new UF and conventional methods. EPS recovery by the new method ranged from 83% to 104% for EPS added in the concentration range 40-1,500 mg/l in 0.1 M NaCl solution or culture medium. The UF method was rapid (8 h), accurate and simple, and required only a small sample volume (1-5 ml). A very high maximum EPS production was measured in SWP by both the UF and conventional methods (1,718 and 1,755 mg/l). PMID- 11759694 TI - Study of the production of fructose and ethanol from sucrose media by Saccharomyces cerevisiae. AB - The production of ethanol and enriched fructose syrups from a synthetic medium with various sucrose concentrations using the mutant Saccharomyces cerevisiae ATCC 36858 was investigated. In batch tests, fructose yields were above 90% of theoretical values for the sucrose concentrations between 35 g/l and 257 g/l. The specific growth rates and biomass yields were from 0.218 to 0.128 h(-1) and from 0.160 to 0.075 g biomass/g of glucose and fructose consumed, respectively. Ethanol yields were in the range of 72 to 85% of theoretical value when sucrose concentrations were above 81 g/l. The volumetric ethanol productivity was 2.23 g ethanol/(l h) in a medium containing 216 g/l sucrose. Fructo-oligosaccharides and glycerol were also produced in the process. A maximum fructo-oligosaccharides concentration (up to 9 g/l) was attained in the 257 g/l sucrose medium in the first 7 h of the fermentation. These sugars started to be consumed when the concentrations of sucrose in the media were less than 30% of its initial values. The fructo-oligosaccharides mixture was composed of 6-kestose (61.5%), neokestose (29.7%) and 1-kestose (8.8%). The concentration of glycerol produced in the process was less than 9 g/l. These results will be useful in the production of enriched fructose syrups and ethanol using sucrose-based raw materials. PMID- 11759695 TI - Molecular fingerprinting of bacterial populations in groundwater and bottled mineral water. AB - Monitoring the hygienic quality of drinking waters by determining the concentration of fecal indicators with traditional plate count techniques suffers from important drawbacks. In this work, the potential of PCR-DGGE (polymerase chain reaction - denaturing gradient gel electrophoresis) analysis of 16S rDNA genes to fingerprint the bacterial populations of mineral water and groundwater was investigated. A rapid and simple pretreatment to concentrate and release bacterial DNA prior to PCR was explored. This pretreatment was successful for commercially bottled mineral water. For groundwater, an additional resuscitation step was required to obtain a PCR signal. It was clear that the groundwater under scrutiny contained a more diverse bacterial community than the mineral water. A comparison was made between four kinds of mineral waters and one sample of groundwater using the developed procedures. For each kind of water, bacterial populations cultured on R2A plates were also subjected to PCR-DGGE. Comparison of the fingerprints of the plated samples and the original samples suggested the presence of viable but nonculturable bacteria in the waters. The obtained cluster dendrogram indicated that each kind of water was characterized by a specific molecular fingerprint. The sensitivity of the whole of the procedure was between 10(4) and 10(5) cfu ml(-1) as determined using a pure culture of Escherichia coli. The described PCR-DGGE method can constitute the basis of a new and interesting strategy to monitor in a relatively rapid way (less than 24 h) the bacterial quality of waters such as mineral water, groundwater and certain types of reclaimed water. PMID- 11759696 TI - A GAC biofilm reactor for the continuous degradation of 4-chlorophenol: treatment efficiency and microbial analysis. AB - Using a continuous enrichment technique, a bacterial consortium capable of degrading 4-chlorophenol (4-CP) was obtained from the rhizosphere of Phragmites australis. A granular activated carbon (GAC) biofilm reactor was established using this consortium, and the degradation of 4-CP was investigated under continuous flow operation using a feed of 20-50 mg l(-1) with a hydraulic residence time of 17 min over a 6-month period. Chloride liberation occurred throughout the operation, and the reactor had 4-CP removal efficiencies of 69 100%. Periods of lower performance were attributed to clogging of the column with biomass and the formation of channels. Subsequently, the immobilized biofilm was subjected to a starvation period of 5 months, after which its degradative capacity was still maintained. The microbial consortium was characterized during the continuous flow experiment and dynamic population changes were observed throughout. One isolate recovered from the biofilm was shown to be capable of degrading 4-CP as a sole carbon and energy source. PMID- 11759697 TI - Atrazine degradation by bioaugmented sediment from constructed wetlands. AB - The potential to establish pesticide biodegradation in constructed wetland sediment was investigated. Under microcosm conditions, bioaugmentation of sediment with small quantities of an atrazine spill-site soil (1:100 w/w) resulted in the mineralization of 25-30% of 14C ethyl atrazine (1-10 microg g(-1) sediment) as 14CO2 under both unsaturated and water-saturated conditions; atrazine and its common metabolites were almost undetectable after 30 days incubation. By comparison, unbioaugmented sediment supplemented with organic amendments (cellulose or cattail leaves) mineralized only 2-3% of 14C ethyl atrazine, and extractable atrazine and its common metabolites comprised approximately 70% of the original application. The population density of atrazine degrading microorganisms in unbioaugmented sediment was increased from approximately 10(2)/g to 10(4)/g by bioaugmentation (1:100 w/w), and increased by another 60-fold (6.0x10(5) g(-1)) after incubation with 10 microg g(-1) of atrazine. A high population of atrazine degraders (approximately 10(6) g(-1)) and enhanced rates of atrazine mineralization also developed in bioaugmented sediment after incubation in flooded mesocosms planted with cattails (Typha latifolia) and supplemented with atrazine (3.2 mg l(-1), 1 microg g(-1) sediment). In the absence of atrazine, neither the population of atrazine degraders, nor the atrazine mineralizing potential of bioaugmented sediment increased, regardless of the presence or absence of cattails. Bioaugmentation might be a simple method to promote pesticide degradation in nursery run-off channeled through constructed wetlands, if persistence of degraders in the absence of pesticide is not a serious constraint. PMID- 11759698 TI - Degradation of crude oil by marine cyanobacteria. AB - The marine cyanobacteria Oscillatoria salina Biswas, Plectonema terebrans Bornet et Flahault and Aphanocapsa sp. degraded Bombay High crude oil when grown in artificial seawater nutrients as well as in plain natural seawater. Oil removal was measured by gravimetric and gas chromatographic methods. Around 45-55% of the total fractions of crude oil (containing 50% aliphatics, 31% waxes and bitumin, 14% aromatics and 5% polar compounds) were removed in the presence of these cultures within 10 days. Between 50% and 65% of pure hexadecane (model aliphatic compound) and 20% and 90% of aromatic compounds (anthracene and phenantherene) disappeared within 10 days. Mixed cultures of the three cyanobacterial species removed over 40% of the crude. Additionally, these cultures formed excellent cyanobacterial mats when grown in mixed cultures, and thus have the potential for use in mitigating oil pollution on seashores, either individually or in combination. PMID- 11759699 TI - Phylogenetic diversity of a SRB-rich marine biofilm. AB - This study was conducted to characterize the phylogenetic diversity of a corrosive marine biofilm based on 16S rDNA. Results of phylogenetic analysis indicated that, out of the 112 clones developed, 52 clones (46.4%) were affiliated with two families of sulfate-reducing bacteria: Desulfovibrionaceae and Desulfobacteriaceae. Another 44 clones (39.3%) were affiliated with the Clostridiaceae family of low G+C, gram-positive bacteria. Three clones (2.7%) were closely related to Chlorobium vibrioforme, a green sulfur bacterium. PMID- 11759700 TI - HIV positive health worker wins injunction to preserve anonymity. PMID- 11759701 TI - The rationale for pathogen inactivation treatment of platelet components- introduction. PMID- 11759702 TI - Want fewer regs? Fix the system. PMID- 11759703 TI - IT governance involves top execs. PMID- 11759704 TI - Outsourcing IT is working here. PMID- 11759706 TI - Joy to the rural. PMID- 11759705 TI - Staffing woes begin within. PMID- 11759707 TI - To close or not to close. PMID- 11759708 TI - 1Q[3a]. Is the nation on the cusp of a physician shortage? PMID- 11759709 TI - Code yellow. PMID- 11759710 TI - Army nurse. PMID- 11759711 TI - 2001 contract management survey. AB - For the second year running, hospitals are spending more on clinical outsourcing than on business services. The Eleventh Annual Contract Services Survey shows that, in clinical areas, executives use outsourcing to acquire specialized expertise with cost savings secondary. Reducing costs and FTEs are the primary reasons for outsourcing business operations. Business service contracts are more likely to meet expectations for cost savings. Overall, satisfaction levels are up, but in some areas there's still a lot of room for improvement. This report examines current trends in outsourcing, strategies for the future, satisfaction levels, the decisionmaking process, contract features, and costs. PMID- 11759712 TI - Striking the right balance between innovation and drug price competition: putting the Hatch-Waxman Act into perspective. PMID- 11759713 TI - Striking the right balance between innovation and drug price competition: understanding the Hatch-Waxman Act--an introduction of speakers. PMID- 11759714 TI - Autonomy and the subjective character of experience. AB - In his famous paper, What Is It Like To Be a Bat?, Thomas Nagel argues against a reductive physicalist account of consciousness by highlighting what he calls "the subjective character of experience." In this paper I will argue that Nagel's insight is important for understanding the value placed on patient autonomy in medical ethics. Appreciation of the subjective character experience brings with it the necessity for an epistemological humility with respect to the lives of others and what can be said to be "right" for them. Appreciation of the subjective character of experience lies at the heart of empathy and our capacity to make decisions that genuinely reflect respect for the patient's autonomy. Through the example of a case involving extreme medical intervention, I identify some impediments to the proper recognition of autonomy. These kind of cases highlight the significance of affective responses with respect to the subjective character of experience, and, by extension, to our capacity to imagine and act in accordance with another's perspective. I argue that affective responses are appropriate and needed considerations in the case where one must attempt to assume another's perspective in order to respect autonomy. I conclude that understanding that experience has an irreducibly subjective character is essential to respecting patient autonomy. PMID- 11759715 TI - [Mary Shelley's Frankenstein and Bram Stoker's Dracula: gender and science in literature]. AB - Throughout the ages, literary works have expressed fears and expectations generated by scientific discoveries and have portrayed images and myths about science itself. Several parameters can contribute to these representations of science, including the culture and social class to which the authors of these works belong. We also cannot deny the influence of gender, as due to the fact that the male sphere of action dominates science, male or female authoring can determine a peculiar characterization of the scientific world. In the present work, through a comparative analysis of two important literary works from the 19th century, Frankenstein, by Mary Shelley, and Dracula, by Bram Stoker, the issues concerning the view of science and their relation to gender are highlighted. While Shelley, as a woman, apart from the scientific world, reveals in Frankenstein all her distrust about it, Stoker, the model of a Victorian man, expresses in Dracula his total trust in science. PMID- 11759716 TI - [Nina Rodrigues, epidemiologist: historical study of beriberi outbreaks in a mental asylum in Bahia, Brasil (1897-1904)]. AB - Beriberi outbreaks in the Sao Joao de Deus Asylum, 1897-1904, are presented, focusing on studies by legist physician Nina Rodrigues. The goals were: to trace the steps of the original investigation of an unknown disease; to understand the purpose of excluding mentally ills in an asylum institution. Methodology encompassed occurence narration and qualitative analytical procedures for the documental interpretation of voluntary and involuntary testimonies, combined with statistical treatment of measurable data. Frequent and progressive outbreaks of beriberi have caused two-thirds of the asylum deaths in 1904. The research method included domiciliary visits and interviews with dwellers in the asylum surroundings. Beriberi occurence was frequent among the insane and practically inexistent among the asylum staff, who presented close and long lasting contact with the ills. Nina Rodrigues refuted the declining miasmatic conception which emphasized external conditions, the emergent conception of contagion, and raised the hypothesis of a carential etiology for beriberi. Nina Rodrigues' study is a good historical example of "epidemiological reasoning," with question formulation, building of data bulk guided by working hypothesis, obtained by means of simple and efficient techniques. PMID- 11759717 TI - [Cathedrals to sciences or temples of knowledge? The museums of natural sciences of Cordoba, Argentina, by the end of the 19th century]. AB - The museums of Botany, Mineralogy and Zoology of the Facultad de Ciencias Fisico Matematicas were created along with a world wide phenomenon, defined by some authors as the "museum movement," in a time the basics of this movement were being restructured. Thus, this work intends to go over the building stage of the natural history museums in a peripheral domain --- Cordoba by the end of the 19th century --- in order to partially understand this transition process. The strategy is to analyze the collections and find out how and why they were gathered. Two other aspects are also relevant: the human resources and the funds these institutions were granted. PMID- 11759718 TI - [The biomedical model and the reformulation of the medical curriculum of Universidade Federal Fluminense]. AB - This work reviews the model used as basis for the curricula of medical universities in North and South America as well as in most European countries. Some criticism about this model is identified on the curricular reformulation of the medicine course of Universidade Federal Fluminense (UFF). The review of the document about curricular reformulation of UFF, from 1992, as well as how it compares to its previous curriculum regarding the history of the biomedical model, the curricular theory, and Ludwik Fleck's epistemology, measures the relevance of this reformulation as an alternative to the biomedical model of forming doctors and to the reductionism of the human being to its biological organism. The new curriculum --- with a 25% raise in credit hours and the inclusion of many new practical classes since the beginning of the course --- although still focusing the biological aspects, already shows a more humanist formation and intends to question the "scientifical truths". PMID- 11759719 TI - [Men and women: imagery about sterility in Portuguese America]. AB - This paper discusses old usages and beliefs about sterility in Colonial Brazil. Treated as a curse usually befallen women, sterility was struggled with symbolism and phytotherapy, aiming to "unbock" or "remove the spell" from the craddle of creation. PMID- 11759720 TI - Health status indicators for the year 2000. PMID- 11759721 TI - A model integrated advance directive for health care unto the third generation. PMID- 11759722 TI - Euthanasia and critical decision-making in intensive care units: a comparative organisational research project. PMID- 11759723 TI - Questions on assistance in dying in Germany -- some brief remarks. PMID- 11759724 TI - Third symposium of the European Network for Biomedical Ethics: ethics in human procreation, genetic diagnosis and therapy. Sheffield, 7th-10th January 1999. PMID- 11759725 TI - Mandatory HIV testing of new-borns in the United States. PMID- 11759726 TI - At life's end, many patients are denied peaceful passing. Planning for death: first of two articles. PMID- 11759727 TI - Board of Veterans' Appeals: rules of practice--time for filing substantive appeal. Final rule. AB - This document amends the Rules of Practice of the Board of Veterans' Appeals (Board) relating to the time limit for filing a "substantive appeal." The amendment implements an opinion by the General Counsel of the Department of Veterans Affairs (VA) that, in some cases, when a claimant files additional evidence, the deadline for filing a substantive appeal may be extended. PMID- 11759728 TI - Substance Abuse and Mental Health Services Administration; mental health and substance abuse emergency response criteria. Interim final rule. AB - Section 3102 of the Children's Health Act of 2000, Pub. L. 106-310, amends section 501 of the Public Health Service (PHS) Act (42 U.S.C. 290 aa) to add a new subsection (m) entitled "Emergency Response." This newly enacted subsection 501(m) authorizes the Secretary to use up to, but no more than, 2.5% of all amounts appropriated under Title V of the PHS Act, other than those appropriated under Part C, in each fiscal year to make "noncompetitive grants, contracts or cooperative agreements to public entities to enable such entities to address emergency substance abuse or mental health needs in local communities." Because Congress believed the Secretary needed the ability to respond to emergencies, it exempted any grants,contracts, or cooperative agreements authorized under this section from the peer review process otherwise required by section 504 of the PHS Act. See section 501(m)(1) of the PHS Act. Instead, the Secretary is to use an objective review process by establishing objective criteria to review applications for funds under this authority. Pursuant to Public Law 106-310, the Secretary is required to establish, and publish in the Federal Register, criteria for determining when a mental health or substance abuse emergency exists. In this interim final rule, the Secretary sets out these criteria, as well as the intended approach for implementing this new mental health and substance abuse emergency response authority. The Secretary invites public comments on both the criteria and the approach described in this interim final rule. PMID- 11759729 TI - Effect of the Family and Medical Leave Act on the operation of cafeteria plans. Final regulations. AB - This document contains final regulations relating to cafeteria plans that reflect changes made by the Family and Medical Leave Act of 1993 (Act). The final regulations provide the public with guidance needed to comply with the Act and affect employees who participate in cafeteria plans. PMID- 11759730 TI - Use of resources and postoperative outcome. AB - OBJECTIVE: To characterise those surgical patients who consume one half of all hospital patient days, and to compare their outcome with that of low consumers. DESIGN: A retrospective cohort study. SETTING: Tertiary referral centre, Finland. PATIENTS: 13025 surgical patients who were admitted to a university hospital in Kuopio, Finland, during 1997. INTERVENTIONS: The length of stay below which half of all patient days fell was chosen as a cut-off value to divide patients into low and high consumers. MAIN OUTCOME MEASURES: Hospital and 12-month mortality and standardised mortality ratios (SMR: observed deaths/expected deaths based on the corresponding general population). RESULTS: The 2239 patients (17%) whose length of stay exceeded 9 days (high consumers) took up one half of all patient days. The pattern of resource use varied between operative specialities. At 12 months the SMRs showed excess mortality among high consumers (5.0, 95% confidence interval 4.4 to 5.7) compared with low consumers (2.1, 95% CI 1.9 to 2.3). CONCLUSIONS: Relating the length of stay to the proportion of resources consumed may provide a feasible tool for the recognition of different patterns of use of resources. SMRs may be more relevant measures of outcome than hospital mortality when assessing the efficacy of operative treatment. PMID- 11759731 TI - Smoking and alcohol intake in surgical patients: identification and information in Danish surgical departments. PMID- 11759732 TI - Blood loss in prosthetic hip replacement is not influenced by the AB0 blood group. AB - OBJECTIVE: To find out if there is a correlation between AB0 type and the amount of blood lost at operation. DESIGN: Retrospective study. SETTING: One county and one university hospital, Sweden. SUBJECTS: 540 patients who underwent primary prosthetic hip replacement under regional anaesthesia. Albumin (n = 298) or dextran (n = 242) were used as plasma substitutes. MAIN OUTCOME MEASURES: Estimated blood loss and number of units of red cell concentrates transfused. RESULTS: The characteristics of the study groups were similar. In patients given albumin, the mean (SD) intraoperative loss with blood group 0 (n = 100) was 718 (413) ml and 2.7 (1.9) red cell units were given. Those with other blood groups (n = 198) lost 713 (469) ml and were given 2.5 (2.0) units. In patients given dextran with blood group 0 (n = 82), the intraoperative blood loss was 650 (337) ml, the postoperative loss 480 (222) ml and they received 2.1 (2.1) units. The corresponding values in the patients with other blood groups (n = 160) were 665 (351), 498 (208) and 2.5 (2.1) units. CONCLUSION: Blood group 0 was not associated with increased blood loss. PMID- 11759733 TI - Effect of combining ultrasonography and ultrasound-guided fine-needle aspiration biopsy findings for the diagnosis of thyroid nodules. AB - OBJECTIVE: To assess the accuracy of ultrasonography and cytology in predicting malignancy in thyroid nodules. DESIGN: Prospective open study. SETTING: Thyroid centre, Japan. SUBJECTS: 329 nodules in 309 patients examined by a new ultrasound scanner and ultrasound-guided fine-needle aspiration biopsy. INTERVENTIONS: Comparison of ultrasonographic, cytological, and combined diagnosis with the histological diagnosis. MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of each diagnostic method. RESULTS: The sensitivity, specificity, accuracy were 84%, 87%, 85% for cytological diagnosis, and 82%, 91%, and 87% for ultrasonographic diagnosis. By using ultrasonographic diagnosis when cytological specimens were inadequate or gave false negative results, the sensitivity, specificity, and accuracy went up to 89%, 91%, and 90%, respectively. We could not diagnose follicular carcinomas accurately by combined cytology and ultrasonography. CONCLUSION: The combination of ultrasonography and cytology improves the accuracy of diagnosis of thyroid nodules, but is less effective with follicular tumours. PMID- 11759734 TI - External laryngeal nerve in thyroid surgery: is the nerve stimulator necessary? AB - OBJECTIVE: To find out the incidence and type of external laryngeal nerves during operations on the thyroid, and to assess the role of a nerve stimulator in detecting them. DESIGN: Prospective, non-randomised study. SETTING: Teaching hospital, Malaysia. SUBJECTS: 317 patients who had 447 dissections between early January 1998 and late November 1999. MAIN OUTCOME MEASURES: Number and type of nerves crossing the cricothyroid space, and the usefulness of the nerve stimulator in finding them. RESULTS: The nerve stimulator was used in 206/447 dissections (46%). 392 external laryngeal nerves were seen (88%), of which 196/206 (95%) were detected with the stimulator. However, without the stimulator 196 nerves were detected out of 241 dissections (81%). The stimulator detected 47 (23%) Type I nerves (nerve > 1 cm from the upper edge of superior pole); 86 (42%) Type IIa nerves (nerve < 1 cm from the upper edge of superior pole); and 63 (31%) Type IIb nerves (nerve below upper edge of superior pole). 10 nerves were not detected. When the stimulator was not used the corresponding figures were 32 (13%), 113 (47%), and 51 (21%), and 45 nerves were not seen. If the nerve cannot be found we recommend dissection of capsule close to the medial border of the upper pole of the thyroid to avoid injury to the nerve. CONCLUSION: Although the use of the nerve stimulator seems desirable, it confers no added advantage in finding the nerve. In the event of uncertainty about whether a structure is the nerve, the stimulator may help to confirm it. However, exposure of the cricothyroid space is most important for good exposure in searching for the external laryngeal nerve. PMID- 11759735 TI - Use of composite prostheses in the repair of defects in the abdominal wall: prosthetic behaviour at the peritoneum. AB - OBJECTIVE: To compare the behaviour of two composite biomaterials in rabbit peritoneum. DESIGN: Animal study. SETTING: Faculty of Medicine, University of Alcala, Spain. ANIMALS: 14 white New Zealand white rabbits divided into 2 groups of 7 each. INTERVENTIONS: Defects (7 x 5 cm) involving all the layers of the abdominal wall were created and repaired using Parietex Composite or Vypro prostheses. Fourteen days after implantation, prosthetic specimens were examined by microscopy, and morphometric and biomechanical analysis. MAIN OUTCOME MEASURES: Infection, healing, development of adhesions, and histological appearance of the interface. RESULTS: Firm adhesions were detected after the implant of Vypro while adhesion were loose in the Parietex group. The mean (SD) prosthetic surface area covered by adhesions was significantly greater in the Vypro group 22.3 (2.8) compared with 0.2 (0.02), p <0.01). The neoperitoneum formed after the implant of Parietex was well-organised and homogeneous and covered by a typical mesothelium, while in the Vypro it was disorganised, with a rough texture composed of prosthetic filaments and nodes. The neoperitonum was thicker in the Parietex group 154.0 (5.4) compared with 50.8 (2.3), p <0.05) while higher biomechanical resistance values were recorded in the Vypro group 30.4 (1.9) compared with 15.0 (2.73), p <0.05). CONCLUSIONS: While both biomaterials integrated well with tissue, Parietex behaved better at the peritoneal interface. PMID- 11759736 TI - Treatment of iatrogenic perforations with covered stents in patients with oesophageal cancer. PMID- 11759738 TI - Mortality after open cholecystectomy in patients with cirrhosis of the liver: a population-based study in Denmark. AB - OBJECTIVE: To find out if patients with alcoholic cirrhosis are at greater risk of dying within 30 days of cholecystectomy than patients with non-alcoholic cirrhosis or normal controls. DESIGN: Population-based study. SETTING: Hospitals, Denmark. SUBJECTS: 23103 patients with liver cirrhosis recorded in the Danish National Registry during the period 1977-94, of whom 110 had an open cholecystectomy; a random sample of 1204 patients without cirrhosis taken from all patients who had a cholecystectomy during the study period. MAIN OUTCOME MEASURE: Risk of mortality. RESULTS: In the group with alcoholic cirrhosis the 30 day mortality was 7.7% and for the controls it was 0.9%. In patients with alcoholic cirrhosis the relative risk of death within 30 days was 11.5 (95% confidence interval 2.8 to 47.4) compared with controls, whereas that for patients with non-alcoholic cirrhosis was 1.1 (95% CI 0.1 to 9.8) compared with controls. CONCLUSION: Patients with alcoholic cirrhosis have an 11-fold increased risk of postoperative mortality after undergoing cholecystectomy. PMID- 11759737 TI - Emergency oesophagectomy and proximal deviating oesophagostomy for fulminent mediastinal sepsis. AB - OBJECTIVE: To evaluate an aggressive surgical strategy in patients with mediastinal sepsis as a result of oesophageal leakage. DESIGN: A prospective clinical study. SETTING: University hospital, Sweden. SUBJECTS: 11 consecutive patients who presented with mediastinal sepsis as a result of a damaged oesophagus caused by instrumental perforation in 4 cases and spontaneous rupture in 6 cases during a 6-year period. INTERVENTIONS: Ten patients were treated with oesophagectomy with a diverting proximal oesophagostomy and in one case a primary cervical oesophagogastrostomy was done after emergency resection. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: The median delay from onset of symptoms to admission to the unit was 3 days (range 0-6). All patients required artificial ventilation postoperatively and the stay in the ICU amounted to 12.5 days but only 1 patient died during the postoperative course. All patients have subsequently undergone substernal oesophageal replacement with either a gastric tube or a colonic graft. CONCLUSION: Emergency oesophagectomy and proximal deviating oesophagostomy is a salvage procedure for patients with severe fulminant mediastinal sepsis, and it can be done in selected cases with good results. PMID- 11759739 TI - Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage. AB - OBJECTIVE: To examine the changes in the number of T cells and macrophages in the mucosal lamina propria in the presence or absence of bile in the gastrointestinal tract. DESIGN: Clinical study. SETTING: University hospital, Japan. SUBJECTS: 6 patients with obstructive jaundice who had external biliary drainage (drainage group) and 6 patients with no signs of obstructive jaundice (control group). INTERVENTIONS: Gastrointestinal specimens were taken at the time of operation. MAIN OUTCOME MEASURES: The number of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the lamina propria mucosae in each group measured immunohistochemically. RESULTS: The numbers of CD8 T cells and CD68+ macrophages in the lamina propria of the patients treated by external drainage were significantly less than in the control group (p < 0.01). However, there was no difference in the number of CD4+ T cells between the groups (p = 0.45). CONCLUSIONS: In the absence of bile, mucosal immune function fails as a result of reduced numbers of CD8+ T cells and macrophages. PMID- 11759740 TI - Pancreatic tissue perfusion in experimental acute pancreatitis. AB - OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases. PMID- 11759741 TI - Study of the reversibility of endothelial dysfunction in a rat model of diabetes mellitus: experimental treatment by transplantation of pancreatic islets. AB - OBJECTIVE: To study the endothelial dysfunction induced in a rat model of diabetes mellitus, and to find out if transplantation of islet cells is an effective treatment for the endothelial damage. DESIGN: Experimental study. SETTING: University hospital, Spain. ANIMALS: 24 Wistar rats in 3 groups of each: control, diabetic and transplanted. INTERVENTIONS: Diabetes was induced in the diabetic and transplanted animals by intravenous injection of streptozocin 45 mg/Kg. In the transplanted group fresh pancreatic islet from syngeneic donor rats (1200-1500/receptor) were injected intraportally 16 weeks after the induction of diabetes. The rats were killed at 18 weeks. Excision of rings of thoracic aorta, which were contracted with 0(-5) M phenylephrine. Once the maximum contraction had been reached relaxation was induced with 10(-5) M acetylcholine and then 10( 4) M independent nitroprusside endothelial vasodilator was added. MAIN OUTCOME MEASURES: Blood glucose concentrations throughout the experiment. Mean vasodilator response to acetylcholine as an indicator of recovery of endothelial function. RESULTS: The mean (SD) vasodilatation in the control group differed significantly from that in the diabetic group (27.6 (3.9) g compared with 20.1 (3.9) p = 0.002). The transplanted group also differed from the diabetic group (25.8 (3.6) g, p = 0.009). There was no significant difference between the transplanted group and the control group (p = 0.33). CONCLUSION: In rats diabetes mellitus causes considerable endothelial damage, which can be reversed by transplantation of pancreatic islets. PMID- 11759742 TI - Neutrophil adhesion molecules in colorectal surgery: effect of filgrastim given perioperatively. AB - OBJECTIVE: To assess whether the postoperative expression of neutrophil adhesion molecules CD11b/CD18 (Mac-1) and CD62L (L-selectin) would differ in peripheral blood, peritoneal fluid and wound fluid in patients operated on for colorectal conditions, and to analyse the effect of perioperative filgrastim on their expression. DESIGN: Prospective randomised double-blind placebo-controlled clinical study. SETTING: University hospital, Finland. SUBJECTS: Thirty consecutive patients undergoing elective colorectal operations (15 in each group). INTERVENTIONS: The patients were prospectively randomised to receive either filgrastim or placebo. Expression of neutrophil adhesion molecules was measured 48 hours postoperatively in peripheral blood, peritoneal fluid, and wound fluid by flow cytometry. RESULTS: Postoperative neutrophil CD11b/CD18 expression was higher in both wound fluid and peritoneal fluid than in peripheral blood in the placebo group. Simultaneously, the expression of neutrophil CD62L was higher in peripheral blood than in peritoneal fluid or wound fluid in both groups. Filgrastim caused increased postoperative expression of neutrophil CD11b/CD18 in peripheral blood but not in peritoneal fluid or wound fluid. CONCLUSIONS: Postoperative expression of neutrophil adhesion molecules differs at the local operation site from that in peripheral blood. Filgrastim increases only blood neutrophil CD11b/CD18 expression. PMID- 11759744 TI - Giant goitre. PMID- 11759743 TI - Early outcome after minilaparotomy for the treatment of rectal cancer. AB - OBJECTIVE: To compare early outcomes of the minilaparotomy approach to the resection of rectal cancer with those of conventional laparotomy. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 18 patients who had complete resection through a minilaparotomy and 20 who had a conventional laparotomy served as the study and the control groups, respectively. Patients who were overweight or morbidly obese (body mass index >25) were excluded from the study. INTERVENTIONS: Complete resection through a skin incision less than 7 cm in length, or a conventional incision. MAIN OUTCOME MEASURES: Early postoperative outcomes. RESULTS: Postoperative time intervals to standing, walking, passing flatus, and removal of the urinary catheter, and analgesic requirements were significantly less in the minilaparotomy group (p = 0.007, p = 0.004, p = 0.02, p = 0.002, and p = 0.05, respectively). CONCLUSIONS: The minilaparotomy for complete resection of rectal cancer is less invasive than conventional laparotomy, and provides an attractive alternative in highly selected patients who are not overweight. PMID- 11759745 TI - Postoperative perineal hernia repairing technique. PMID- 11759746 TI - Metastatic retroperitoneal and mediastinal fibrosis as first sign of recurrence of breast cancer. PMID- 11759747 TI - Study of the authenticity of commercial wine yeast strains by molecular techniques. AB - mtDNA restriction analysis has been carried out with 45 different commercial Saccharomyces wine yeast strains. The analysis with Hinf I provided unique profiles for 17 of the 45 strains and can therefore be considered as individual strains. Nevertheless, among the remaining 28 strains, only eight mtDNA restriction patterns appeared. These strains were subjected to electrophoretic karyotyping and PCR amplification of delta sequences. We concluded that the maximum discriminatory power was obtained when the results of the three techniques were combined, giving 13 different composite patterns for the 28 strains under study. The results showed evidence of mistakes during production or fraudulent practices by yeast producers, since only 30 individual strains have been identified among the 45 Saccharomyces wine yeast strains commercialised by different companies. Additionally, commercial starters of Saccharomyces uvarum and Saccharomyces bayanus have been re-identified as Saccharomyces cerevisiae. PMID- 11759748 TI - Growth characteristics of Candida kefyr and two strains of Lactococcus lactis subsp. lactis isolated from Zimbabwean naturally fermented milk. AB - Lactic acid bacteria (LAB) and yeasts constitute part of the microflora in Zimbabwean traditional fermented cows' milk, amasi. The present study was carried out to investigate the growth characteristics of Candida kefyr 23, Lactococcus lactis subsp. lactis biovar. diacetylactis C1 and L. lactis subsp. lactis Lc261, previously isolated from amasi, in ultrahigh temperature (UHT)-treated cows' milk. The strains were inoculated into the UHT milk as both single and yeast PMID- 11759749 TI - Evaluation of the ability of lysozyme and nisin to control meat spoilage bacteria. AB - The antimicrobials lysozyme, nisin, and mixtures of the two were studied to ascertain their abilities to control the growth of the meat-borne spoilage bacteria, Brochothrix thermosphacta B2 and Carnobacterium sp. 845. The goal was to optimize an antimicrobial for potential use in preservation of fresh meats. Their efficacies were evaluated in APT broth, in a meat juice extract and on cores of lean and fat pork tissue. Both lysozyme and nisin alone as well as mixtures of the two effectively inhibited B. thermosphacta B2 at 250 microg/ml in APT broth, the lowest concentration evaluated, for 10 days at 2 degrees C. In the presence of 500 microg/ml lysozyme, B. thermosphacta B2 grew after 12 days incubation. Only 125 microg of antimicrobial/ml was required to inhibit B. thermosphacta B2 for 27 days at 2 degrees C in pork juice. An estimated surface concentration of 130 microg/cm2 of each of the antimicrobials effectively inhibited B. thermosphacta B2 on inoculated cores of fat and lean pork tissue when the cores were incubated in vacuum packages for 6 weeks at 2 degrees C. In APT broth and in pork juice, lysozyme showed no antimicrobial activity against Carnobacterium sp. 845 at concentrations of 500 and 1000 microg/ml, respectively. Nisin and mixtures of the two antimicrobials inhibited Carnobacterium sp. 845 so that its numbers were at least 3 log units lower than untreated samples after 26 and 27 days incubation for APT and pork juice, respectively. The antimicrobial effect was concentration dependent. On lean pork tissue, numbers of Carnobacterium sp. 845 were significantly lower than untreated samples or samples treated with 195 microg/cm2 lysozyme when 260 microg/cm2 of a 1:3 (w/w) ratio of nisin to lysozyme was introduced to the cores. The inhibitory effect lasted for 14 of 42 days incubation in vacuum at 2 degrees C. On fat tissue, both lysozyme alone and the 1:3 nisin/lysozyme mixture inhibited Carnobacterium sp. 845 for 21 days storage in vacuum at 2 degrees C. On fat and lean tissue, mixtures of nisin and lysozyme would be more effective antimicrobials than either nisin or lysozyme alone. PMID- 11759750 TI - Validation of ISO method 11290 part 2. Enumeration of Listeria monocytogenes in foods. AB - The European and International Standard method for the enumeration of Listeria monocytogenes, described in EN ISO 11290 Part 2: 1998 [EN ISO 11290-2 Microbiology of Food and Animal Feedingstuffs-Horizontal Method for the Detection and Enumeration of L. monocytogenes: Part 2. Enumeration; International Organisation for Standardisation, Geneva.] was validated by order of the European Commission (Standards, Measurement and Testing Fourth Framework Programme Project SMT4-CT96-2098). The objective was to determine the precision of the method in terms of repeatability (r) and reproducibility (R) using three different food types inoculated with various levels of L. monocytogenes and a typical background flora. The results are intended for publication in the associated standards. Cheese, meat, dried egg powder and reference materials were examined by 21 laboratories in 16 countries in Europe. Each participant received eight test materials per food type: blind duplicates at four inoculum levels (0, 10(2), 10(3), 10(4) cfu/g). In addition, two reference materials containing L. monocytogenes were included in the study. All test materials were subjected to stringent homogeneity and stability testing before being used in the collaborative trial. Participants were required to use only PALCAM agar for enumeration of L. monocytogenes, as prescribed by the reference method. Statistical analyses has been performed using a newly introduced approach for food microbiology (draft standard prEN ISO 16140 [prEN ISO 16140 Microbiology of Food and Animal Feedingstuffs-Protocol for the Validation of Alternative Methods, International Organisation for Standardisation, Geneva.], the precision data being calculated using robust estimates. Overall values for repeatability (r) of EN ISO 11290-2 when used with food test materials were r = log10 0.58 (expressed as an absolute difference between log10-transformed test results) or r = 3.8 (expressed as an absolute ratio between test results on the normal scale). For the reference materials (capsules containing approximately 5000 cfu), r = log10 0.34 (expressed as an absolute difference between log10-transformed test results) or r = 2.2 (expressed as an absolute ratio between test results on the normal scale). Overall values for reproducibility (R) of EN ISO 11290-2 when used with food test materials were R = log10 0.81 (expressed as a difference between log10 transformed test results) or R = 6.5 (expressed as an absolute ratio between test results on the normal scale). For the reference materials, R = log10 0.51 (expressed as a difference between log10-transformed test results) or R = 3.2 (expressed as an absolute ratio between test results on the normal scale). Further studies have been initiated by ISO TC34/SC9 to try to enhance the isolation of L. monocytogenes from foods and improve the confirmation procedures. PMID- 11759751 TI - Growth of Salmonella enteritidis in artificially contaminated eggs: the effects of inoculum size and suspending media. AB - Growth profiles of two isolates of Salmonella enteritidis phage type (PT) 4 inoculated into either the albumen of whole shell eggs or into separated albumen were found to be markedly affected by the size of the inoculum and the composition of the medium used to suspend the cells prior to inoculation. Using our model with an inoculum of two cells, multiplication of the Salmonella was not seen in 93% of eggs held at 20 degrees C for 8 days. In approximately 7% of eggs, however, growth occurred during the 8 days of storage. If the inoculum equaled or exceeded 25 cells per egg when eggs were subsequently stored at 20 degrees C, or 250 cells per egg when eggs were stored at 30 degrees C, high levels of growth of Salmonella in the egg occurred significantly more frequently than when the inoculum was two cells. High levels of growth were also seen more frequently if the inoculum was suspended in buffered peptone water or maximal recovery diluent rather than in phosphate buffered saline. Growth of Salmonella in separated albumen occurred very infrequently (1.1% of samples) at low inoculum levels and did not become significant until the inoculum was 250 cells or greater. Growth in the albumen was unaffected by the composition of the suspending medium. Provided that the inoculum was approximately 2 cells per egg and the bacteria were suspended in PBS, observed growth profiles of S. enteritidis inoculated into the albumen of whole eggs resembled those in naturally contaminated eggs. PMID- 11759752 TI - Automated immunomagnetic separation and microarray detection of E. coli O157:H7 from poultry carcass rinse. AB - We describe the development and application of an electromagnetic flow cell and fluidics system for automated immunomagnetic separation (IMS) of Escherichia coli O157:H7 directly from poultry carcass rinse. We further describe the biochemical coupling of automated sample preparation with nucleic acid microarrays. Both the cell concentration system and microarray detection method did not require cell growth or enrichment from the poultry carcass rinse prior to IMS. Highly porous Ni foam was used to enhance the magnetic field gradient within the flow path, providing a mechanism for immobilizing immunomagnetic particles throughout the fluid rather than the tubing wall. A maximum of 32% recovery efficiency of non pathogenic E. coli was achieved within the automated system with 6 s cell contact times using commercially available antibodies targeted against the O and K antigens. A 15-min protocol (from sample injection though elution) provided a cell recovery efficiency that was statistically similar to > I h batch captures. O157:H7 cells were reproducibly isolated directly from poultry carcass rinse with 39% recovery efficiency at 10(3) CFU ml(-1) inoculum. Direct plating of washed beads showed positive recovery of O157:H7 directly from poultry carcass rinse at an inoculum of 10 CFU ml(-1). Recovered beads were used for direct polymerase chain reaction (PCR) amplification and microarray detection, with a process-level detection limit (automated cell concentration though microarray detection) of < 10(3)CFU ml(-1) in poultry carcass rinse. PMID- 11759753 TI - The occurrence of enteric pathogens and Aeromonas species in organic vegetables. AB - A range of commercially available organic vegetables (n = 86) was examined for the presence of Salmonella, Campylobacter, Escherichia coli, E. coli O 157. Listeria and Aeromonas spp., to provide information on the occurrence of such organisms in organic vegetables in Northern Ireland. The study was not designed to quantify such organisms or to compare occurrence with conventionally farmed vegetables. Standard enrichment techniques were used to isolate and identify enteric pathogens and Aeromonas species. No Salmonella, Campylobacter, E. coli. E. coli O 157, Listeria were found in any of the samples examined. Aeromonas species were isolated from 34% of the total number of organic vegetables examined. Many (64%) of the organic vegetables examined were "ready-to-eat" after minimal processing, i.e., washing. Aeromonas spp. was isolated from 41% of these vegetables. Aeromonas spp. was not recovered from certain vegetable types. The most commonly isolated species of Aeromonas was Aeromonas schubertii with 21.0% of all samples contaminated with this species; 5.8% of samples contained A. hydrophila, 5.8% A. trota, 3.5% A. caviae and 2.3% contained A. veronii biovar veronii. Although Aeromonas species are frequently detected in organic vegetables, the absence of accepted enteric pathogens was encouraging, and does not support the allegation of organic foods being of high risk due to the farming methods used. PMID- 11759754 TI - The effect of inoculum size on the lag phase of Listeria monocytogenes. AB - The effect of inoculum size on population lag times of Listeria monocytogenes was investigated using the Bioscreen automated microtitre plate incubator and reader. Under optimum conditions, lag times were little affected by inoculum size and there was little variation between replicate inocula even at very low cell numbers. However, in media containing inhibitory concentrations of NaCl, both the mean lag time and variation between replicate inocula increased as the inoculum size became smaller. The variation in lag time of cells within a population was investigated in more detail by measuring the distribution of detection times from 64 replicate inocula containing only one or two cells capable of initiating growth. The variance of the lag time distribution increased with increasing salt concentration and was greater in exponential than in stationary phase inocula. The number of cells required to initiate growth increased from one cell under optimum conditions to 10(5) cells in medium with 1.8 M NaCl. The addition of spent medium from a stationary phase culture reduced the variance and decreased lag times. The ability to initiate growth under severe salt stress appears to depend on the presence of a resistant sub-fraction of the population, although high cell densities assist adaptation of those resistant cells to the unfavourable growth conditions by some unspecified medium conditioning effect. These results are relevant to the prediction of lag times and probability of growth from low numbers of stressed cells in food. PMID- 11759755 TI - Occurrence of Listeria monocytogenes in food in Chile. AB - Out of 2145 food samples analysed 77 were found contaminated with Listeria monocytogenes in Santiago, Chile. Samples were: 603 ice-cream (3.5% contaminated), 256 soft cheese (0.8%), 155 hard cheese (0%), 229 baby milk bottles (0%), 634 processed meat products (3.6%) and 268 crustaceous shellfish (11.6%). Three different isolation media were used: for 318 samples, Modified McBride Agar (MMA), Lithium chloride Phenylethanol Moxalactam agar, and Polymyxin Acriflavine Lithium chloride Ceftazidime Aesculin Mannitol agar; for 1827 samples MMA was replaced by Listeria Selective Agar Oxford Formulation. Isolates were classified as follow: serovar 1/2a (25 isolates), serovar 4b (20), serovar 1/2b (19), serovar 3b (7), serovar 1/2c (2), untypable (4). A high variety of phagovars was detected although 52% of strains was untypable. PMID- 11759756 TI - Microbial diversity in smoked salmon examined by a culture-independent molecular approach--a preliminary study. AB - Microbial biodiversity in sliced vacuum-packed cold smoked salmon was investigated using culture-independent molecular biology techniques. Sliced smoked salmon was stored for 25 days after being packed at 4 degrees C. DNA was extracted from sliced vacuum-packed cold smoked salmon. PCR DNA amplification were carried out using universal eubacterial primers corresponding to Escherichia coli 16S rRNA gene. 16S rRNA genes were amplified, cloned in E. coli and compared using Amplification Ribosomal DNA Restriction Analysis (ARDRA). 106 clones were studied and classified into 13 Operational Taxonomic Units (OTUs). Sequences obtained to describe those 13 OTUs were compared to GenBank data. They indicated the presence of Vibrio species. Enterobacteraceae and also marine psychrophilic clones related to Alteromonas macleodii, which were not encountered within cultures, but no Gram-positive species have been obtained. Those results indicate that bias in description of microbial diversity may be encountred in both molecular and cultural techniques. PMID- 11759757 TI - Acid adaptation and temperature effect on the survival of E. coli O157:H7 in acidic fruit juice and lactic fermented milk product. AB - In this study, two strains of Escherichia coli O157:H7, (ATCC 43889 and ATCC 43895) were acid adapted at pH 5.0 in tryptic soy broth (TSB) for 4 h. Commercial products of mango juice (pH 3.2), asparagus juice (pH 3.6), Yakult--a diluted milk fermented drink (pH 3.6), and low-fat yoghurt (pH 3.9) were inoculated with acid-adapted or nonadapted cells of E. coli O157:H7. Survival of the inoculated E. coli O157:H7 in these commercial food products during storage at 25 or 7 degrees C was examined. It was found that although survival of the acid-adapted and nonadapted E. coli O157:H7 ATCC 43895 in asparagus juice during storage at 7 degrees C did not show marked difference, in general, acid adaptation and low temperature enhanced the survival of E. coli O157:H7 in both the commercial fruit juices tested. On the contrary, acid adaptation reduced the survival of both the strains of the test organism in Yakult and low-fat yoghurt stored at 7 degrees C. Besides, E. coli O157:H7 ATCC 43895 survived longer than ATCC 43889 in all the products examined, regardless of the storage temperature and acid adaptation. PMID- 11759758 TI - Isolation and polymerase chain reaction-based detection of Campylobacter jejuni and Campylobacter coli from poultry in the Philippines. AB - The polymerase chain reaction (PCR) and the conventional culture method of detecting thermophilic Campylobacter species in duck and chicken samples from two locations in the province of Laguna, Philippines, were compared. Three Campylobacter jejuni and five C. coli strains were isolated from a total of 135 duck and chicken samples from both methods. The PCR technique, however, was found to be more sensitive, accurate and rapid than the conventional culture method. The specificity of two sets of published primers, C442-C490 (specific for C. jejuni, C. coli and C. lari) and CL2-CR3 (specific for C. jejuni) were confirmed with reference and field strains. To improve detection, a lysate was prepared by boiling cells in Triton X-100, and then used as template for PCR to detect Campylobacter from spiked and naturally contaminated chicken rinse. For spiked chicken samples, a 17-h Meuller-Hinton Broth enrichment for the chicken rinse resulted in an improved sensitivity at 31.7 CFU/g using C442-C490. This enrichment-PCR tandem also detected thermophilic Campylobacter from 1 out of 21 native chicken samples from a wet market. To our knowledge, this is the first report of thermophilic Campylobacter isolation from poultry in the Philippines. The approaches described here could serve as a basis for future surveillance and/or epidemiological studies on this emerging foodborne pathogen. PMID- 11759759 TI - Mould contaminants on Jarlsberg and Norvegia cheese blocks from four factories. AB - Visible mould from 225 blocks of the Norwegian semi-hard cheeses Jarlsberg and Norvegia from four factories were subcultured and identified. Altogether 23 different fungal species were detected. The two most important contaminating species were Penicillium commune and P. palitans, constituting 21.4% and 17.9% of the total isolates, respectively. The other dominating contaminants were P. roqueforit spp. roqueforti, Geotrichum candidum, P. solitum and P. crustosum. These species, together with P. commune and P. palitans, represented 80.9% of the total isolates. P. commune, P. palitans, P. roqueforti spp. roqueforti and P. solitum were most common contaminants on cheese produced in all four factories, while G. candidum was found to be important on Jarlsberg cheese from only one factory. P. crustosum was one of the dominating species on Norvegia cheese. PMID- 11759760 TI - Antimicrobial susceptibilities of isolates of Staphylococcus aureus, Listeria species and Salmonella serotypes associated with poultry processing. AB - The broth microdilution method was used to determine the activities of selected antimicrobial agents used in the South African poultry industry (danofloxacin, neomycin, chlortetracycline, oxytetracycline, tylosin and colistin) and vancomycin against bacterial isolates previously obtained from carcasses and selected equipment surfaces and environmental sources associated with poultry processing. The antimicrobial susceptibilities of 38 isolates of Staphylococcus (S.) aureus, 25 Listeria (L.) innocua, 18 L. monocytogenes, and 62 isolates belonging to six Salmonella (Salm.) serotypes (Salm. agona, Salm. blockley, Salm. enteritidis, Salm. isangi, Salm. reading and Salm. typhimurium) were determined. The most active antimicrobial agent against all the isolates tested was danofloxacin with minimum inhibitory concentrations (MICs) for 90% of the isolates (MIC90) not exceeding 0.25 and 2 microg/ml for gram-negative and gram positive isolates, respectively. Conversely, high MICs were recorded for all the isolates tested against chlortetracycline and oxytetracycline (MIC90 range of 32 to > 512 microg/ml), except for the L. monocytogenes and Salm. enteritidis isolates (MIC range of < or = 0.5-4 microg/ml). Neomycin was found to be active against S. aureus, L. innocua, L. monocytogenes, Salm. enteritidis and Salm. isangi isolates, with MICs not exceeding 8 microg/ml. MIC ranges for tylosin and vancomycin, which were only tested against the gram-positive isolates, were from 1 to > 512 microg/ml and from 1 to 4 microg/ml, respectively. The MIC range for the remaining antimicrobial agent, colistin, which was only tested against the Salmonella isolates, was 0.5-16 microg/ml. The lack of MIC breakpoints for the antimicrobial agents used in the poultry industry did not allow for definite conclusions as to the level of resistant bacteria associated with poultry carcasses and the processing environment in this study. PMID- 11759761 TI - Modeling non-linear survival curves to calculate thermal inactivation of salmonella in poultry of different fat levels. AB - Survival curves of a cocktail of eight serotypes of Salmonella in ground poultry of different fat levels (1-12%), when heated rapidly to specified temperatures (58-65 degrees C), were examined. Because many of the survival curves were concave, values for two parameters: the asymptotic D-value and the "lag" times were estimated and used to develop secondary models for estimating the time needed to obtain a 7 log10 relative reduction as a function of fat level and temperature. To compute the necessary time, at a given temperature and fat level, the estimated lag time should be added to the product of 7 and the estimated asymptotic D-value. A model was also developed for estimating the standard error of the estimated times, so that upper confidence bounds for the necessary times can be computed. It was found that lag times increase with higher fat levels. The effect of fat on D-values depended on the species; it is estimated that, for a given increase of fat level, the increase of the D-value would be greater for ground chicken than that for ground turkey. In addition, there was a statistically significant species effect on D-values, with higher D-values for ground turkey than for ground chicken at the higher temperatures studied. The thermal death curves displayed a non-linear tendency, however, for estimation purposes, a linear curve was assumed. There was not a statistically significant interaction effect of fat levels and temperatures on D-values, thus, for modeling, it was assumed that z-values were not dependent on the fat levels. The z-values for ground chicken and turkey were estimated to be 5.5 degrees C and 6.1 degrees C, respectively, and are statistically significantly different. These findings should have substantial practical importance to food processors of cooked poultry, allowing them to vary their thermal treatment of ready-to-eat poultry products in a safe manner. PMID- 11759762 TI - Biological control of postharvest pear diseases using a bacterium, Pantoea agglomerans CPA-2. AB - Epiphytic microorganisms isolated from the fruits and leaf surfaces of apples and pears were screened for antagonistic activity against Penicillium expansum on pears. From 247 microorganisms tested for antagonistic properties against P. expansum, a bacterium strain identified as Pantoea agglomerans (CPA-2) was selected. This bacterium was very effective against Botrytis cinerea, P. expansum and Rhizopus stolonifer. Complete control at the three tested concentrations (2 x 10(7), 8 x 10(7) and 1 x 10(8) CFU ml(-1)) was obtained on wounded pears inoculated with 10(3), 10(4) and 10(5) conidia ml(-1) of P. expansum and R. stolonifer. At 8 x 10(7) CFU ml(-1), Pan. agglomerans reduced B. cinerea decay by more than 80% at the three concentrations of the pathogen. In over 3 years of experiments in semicommercial trials, Pan. agglomerans provided excellent control against B. cinerea and P. expansum under cold storage, either in air or in low oxygen atmospheres. Equal control was obtained with Pan. agglomerans at 8 x 10(7) CFU ml(-1), as with the fungicide imazalil at commercial doses, against both pathogens. Pan. agglomerans grew well inside wounds on pears at both room and cold temperatures and under modified atmospheres. In contrast, it grew poorly on the surface of intact fruit. PMID- 11759763 TI - Prevalence and characteristics of shigatoxin-producing Escherichia coli and Listeria monocytogenes strains isolated from minced meat in Switzerland. AB - A total of 400 minced meat samples from 240 small butcheries in Switzerland were collected and analysed for the presence of Shigatoxin-producing E. coli (STEC) and Listeria monocytogenes. The samples comprised 211 samples of minced beef and 189 samples of minced pork. Shigatoxin-producing E. coli was isolated from 7/400 (1.75%) samples. In particular, 5/211 (2.3%) minced beef samples and 2/189 (1%) minced pork samples were contaminated. Serotyping of the seven strains yielded five different serotypes. but none of the strains belonged to O157:H7. Two STEC strains harboured stx1 and stx2 and five strains harboured stx2c genes. Furthermore, four strains harboured one or more additional virulence factors. However, none of the strains was positive for eae. L. monocytogenes was isolated from 43/400 (10.75%) samples. Nineteen of the 43 strains belonged to serotype 1/2a, two to serotype 1/2b, 12 to serotype 1/2c and 10 to 4b. Forty-two strains harboured the Lhly and 43 strains the plcA genes. Macrorestriction analysis of the L. monocytogenes strains using SmaI yielded 12 different PFGE-patterns. The predominating pattern G was associated to the serotype 1/2c. PMID- 11759764 TI - Histamine formation by Tetragenococcus muriaticus, a halophilic lactic acid bacterium isolated from fish sauce. AB - We examined histamine formation in cultures of Tetragenococcus muriaticus, a halophilic lactic acid bacterium isolated from fish sauce. T. muriaticus formed histamine in low acidity (pH 5.8), O2 limiting conditions with optimal NaCl and glucose concentrations of 5-7% (w/v) and above 1%, respectively. Histamine formation could not be prevented even at 20% (w/v) NaCl, indicating that NaCl could not prevent histamine formation by this bacterium. A conspicuous amount of histamine accumulated only during the late stationary phase regardless of the growth conditions. Studies of cell suspension experiments confirmed the results obtained from cultured cells. PMID- 11759765 TI - Use of a bacteriocin-producing transconjugant as starter in acceleration of cheese ripening. AB - The non-conjugative 46 kb plasmid that encodes the biosynthesis of lacticin 3147 in Lactococcus lactis IFPL105 has been transferred to the starter L. lactis IFPL359, used in goat's milk cheesemaking. The accelerating effect exerted on proteolysis and development of sensory characteristics of semi-hard cheese by the bacteriocin-producing transconjugant L. lactis IFPL3593 (Lac+ Bac+ Imm+), which is able to induce cell lysis in starter adjuncts with high peptidase activity, has been studied. It has been demonstrated that the use of IFPL3593 as starter accelerates cheese ripening as it increases the level of amino nitrogen correlated with early cell lysis of adjuncts. The fact that the bacteriocin producing microorganism used is immune to the bacteriocin. allowed proper acidification of the curd without altering the cheese-making process. PMID- 11759766 TI - Performance of mycological media in enumerating desiccated food spoilage yeasts: an interlaboratory study. AB - Dichloran 18% glycerol agar (DG18) was originally formulated to enumerate nonfastidious xerophilic moulds in foods containing rapidly growing Eurotium species. Some laboratories are now using DG18 as a general purpose medium for enumerating yeasts and moulds, although its performance in recovering yeasts from dry foods has not been evaluated. An interlaboratory study compared DG18 with dichloran rose bengal chloramphenicol agar (DRBC), plate count agar supplemented with chloramphenicol (PCAC), tryptone glucose yeast extract chloramphenicol agar (TGYC), acidified potato dextrose agar (APDA), and orange serum agar (OSA) for their suitability to enumerate 14 species of lyophilized yeasts. The coefficient of variation for among-laboratories repeatability within yeast was 1.39% and reproducibility of counts among laboratories was 7.1%. The order of performance of media for recovering yeasts was TGYC > PCAC = OSA > APDA > DRBC > DG 18. A second study was done to determine the combined effects of storage time and temperature on viability of yeasts and suitability of media for recovery. Higher viability was retained at -18 degrees C than at 5 degrees C or 25 degrees C for up to 42 weeks, although the difference in mean counts of yeasts stored at -18 degrees C and 25 degrees C was only 0.78 log10 cfu/ml of rehydrated suspension. TGYC was equal to PCAC and superior to the other four media in recovering yeasts stored at -18 degrees C, 5 degrees C, or 25 degrees C for up to 42 weeks. Results from both the interlaboratory study and the storage study support the use of TGYC for enumerating desiccated yeasts. DG18 is not recommended as a general purpose medium for recovering yeasts from a desiccated condition. PMID- 11759767 TI - Exposure of Listeria monocytogenes within an epidemic caused by butter in Finland. AB - Data on the levels of bacteria and the amounts of food consumed in food-borne outbreaks provides an excellent opportunity to study the effects of exposure to Listeria monocytogenes. Between June 1998 and April 1999, an outbreak caused by L. monocytogenes serotype 3a in butter occurred in Finland. The majority of the cases were immunocompromised and hospitalized at the Helsinki University Central Hospital (HUCH), where 7-g butter packages produced by a dairy plant were used as the only butter brand. The butter had also been sold to 10 other central hospitals as well as to the retail market. Based on the data on hospital stay, butter consumption and the qualitative and quantitative analyses of L. monocytogenes in butter, the attack rates and exposure were estimated. Incubation studies on the naturally contaminated small butter packages showed that the levels found in the packages at the time of detection of the outbreak could reliably be used for these estimations. However, the levels of L. monocytogenes in 500-g packages increased. The attack rate among HUCH patients varied from 70 to 117 cases per 1000 patients at risk, depending on which estimate of the contamination level of butter (100-60%) was used. The highest single dose (7.7 x 10(4) CFU in one meal) could have been sufficient to cause the listeriosis cases at HUCH. However, this data also supports another hypothesis, according to which these listeriosis cases were caused by a prolonged daily consumption of contaminated butter during the hospital stay. The estimated daily dose, based on the hospital kitchen data or the highest detected level in a wholesale sample (11,000 CFU/g), would have varied from 1.4 x 10(1) to 2.2 x 10(3) CFU/day or from 2.2 x 10(4) to 3.1 x 10(5) CFU/day, respectively. The choice of the hypothesis has a crucial impact on the interpretation of this data for the dose-response estimations as well as for the discussion on Food Safety Objectives. Due to the susceptibility of hospital patients, special care must be taken in order to avoid even low levels of L. monocytogenes in food served. PMID- 11759768 TI - Effects of anisometropia on binocularity. PMID- 11759769 TI - Sensory strabismus--eso or exo? AB - PURPOSE: The type of horizontal strabismus from loss or impairment of vision is thought to depend on patient age at the time of vision loss. Association between the age at onset of vision loss and development of esotropia vs exotropia will be determined. METHODS: Patients with a diagnosis of sensory strabismus and visual acuity of 20/40 or poorer were reviewed as well as patients with diagnoses consistent with the development of sensory strabismus. Parameters considered were age at onset of vision loss and type of strabismus. Patients were excluded if the age at onset was not clear. RESULTS: Of 123 patients with sensory strabismus reviewed: 82 (67%) had unilateral vision loss; 41 (33%) had bilateral vision loss; 75 (61%) had congenital vision loss; 50 (67%) developed esotropia; 25 (33%) developed exotropia; 48 (39%) had acquired vision loss; 5 (10%) developed esotropia; and 43 (90%) developed exotropia. A significant difference was noted between age at onset and type of horizontal strabismus (X2= 37.44; P <.0001). CONCLUSION: Of patients with congenital vision loss, 67% developed sensory esotropia and 33% developed sensory exotropia. Of those with acquired vision loss, 10% developed sensory esotropia and 90% developed sensory exotropia. Patients with congenital vision loss are significantly more likely to develop esotropia, P <.005, and those with acquired vision loss are significantly more likely to develop exotropia, P <.001. PMID- 11759770 TI - Cross polarized spectacles in photosensitive epilepsy. AB - PURPOSE: To investigate the role of cross polarized spectacles in the treatment of photosensitivity demonstrable by EEG. METHOD: Patients receiving an EEG who tested positive for photosensitivity were invited to participate in the study. The most sensitive light flicker frequency causing a photic response was determined for each patient. Stimulation was repeated with 2 different pairs of spectacles--1 conventionally polarized and the other cross polarized. An EEG was obtained in each case and reported by a neurophysiologist who was unaware of the identity of the 2 types of spectacles. RESULTS: We tested 19 patients, 8 to 18 years of age. Two patients did not benefit from either pair of glasses. In 17 patients, the photic response was greatly diminished or eliminated by polarizing spectacles. In 1 patient, conventional polarized glasses helped, but the cross polarized spectacles did not. In 6 patients, both types of spectacles were equally effective; in 10 patients, cross polarized spectacles were more effective than conventionally polarized spectacles. CONCLUSION: The role of cross polarized spectacles in the management of photosensitivity in a clinical situation merits further investigation. PMID- 11759771 TI - Risk factors associated with complications of orbital surgery in children. AB - PURPOSE: To assess the overall complication rate of orbitotomies performed in children and to determine the nature of complication to identify possible risk factors. METHODS: Thirty children <13 years underwent 33 orbitotomies for space occupying lesions of the orbit or orbital decompression. A detailed evaluation of the surgical procedures and outcomes was conducted. Follow up averaged 2.5 years (range: 6 months to 5 years). RESULTS: The complication rate was 20% (2 of 10 cases) for anterior orbitotomies, 40% (8 of 20 cases) for primary lateral orbitotomies, and 100% (3 of 3 cases) for secondary orbitotomies. Dense amblyopia was noted in 6 of 9 patients. Major complications were frozen eyeball, diplopia, and ptosis. Less serious complications were enophthalmos, internal ophthalmoplegia, dry eye, and eyelid retraction. Six patients underwent extraocular surgery, levator muscle surgery, or both at a later date. CONCLUSION: Although the scope of complications is the same in children as in adults, the frequency of cystic benign lesions and small orbits in children can cause more frequent serious complications. Additionally, dense amblyopia of a complicated nature makes visual outcome unpredictable. The most significant risk factors identified were the need for a secondary procedure for recurring pathology and the presence of an intraconal lesion. PMID- 11759772 TI - Stimulus deprivation myopia in human congenital ptosis: a study of 95 patients. AB - PURPOSE: To establish differences between the frequency of suspected deprivation myopia in unilateral and bilateral congenital ptosis with and without covered optical axis. METHODS: Ametropia was evaluated in both eyes of 95 patients with congenital ptosis. The amount of refraction was documented as spherical equivalent (100% cycloplegia). Statistical analysis was performed using the chi square and sign tests. RESULTS: In unilateral ptosis, the frequency of myopia was lower (10/68: 15%) than that of hyperopia (58/68: 85%) in the ptotic eye (P <0.001). However, myopia occurred more often in the ptotic eye (10/68: 15%) than in the fellow eye (3/68: 4.4%). Myopic anisometropia was found only in the ptotic eye (5/68 vs 0/68), but was less frequent than hyperopic anisometropia (6/68 vs 8/68). In bilateral ptosis 7/54 myopia as compared with 47/54 hyperopia were observed and 1/27 myopic anisometropia vs 6/27 hyperopic anisometropia. Covered center of the pupil, in children < or = 8 years of age, was associated with myopia more frequently in bilateral than in unilateral ptosis (6/30 vs 1/27). We found a significantly higher rate of myopia <-1 diopter and hyperopia >2 diopter in comparison of children 5 to 7 years old with first-grade school children. CONCLUSIONS: Two expected results were (1) compared with the normal population, an overall higher frequency of myopia in human congenital ptosis; (2) in unilateral ptosis, a higher frequency of myopia in the ptotic, than in the fellow eye. PMID- 11759773 TI - Unilateral rectus resection in the treatment of undercorrected or recurrent strabismus. AB - BACKGROUND: When surgery is required for an undercorrection or for a recurrent strabismus that is in the same direction as the previous deviation, traditional options have included a rerecession of the previously operated muscle(s), a marginal myotomy of the previously operated muscle(s) with or without a resection of the direct antagonist, or a bilateral resection of the antagonist muscles. While many surgeons prefer to perform a bilateral resection for these reasons, a unilateral resection would be a useful approach for small to moderate deviations. METHODS: Data were collected for patients who had undergone a unilateral rectus resection: age, number of prior surgeries, the preoperative deviation, the postoperative deviation at 1 week, 6 weeks, and 6 months, and the amount of surgery performed. An acceptable postoperative result was considered to be any deviation >8 pd. RESULTS: A resection of a single rectus muscle was undergone by 11 3 patients. Complete data were available on 81 of these patients: 60 underwent a unilateral resection of the lateral rectus and 21 underwent a unilateral resection of the medial rectus. Of those patients undergoing a unilateral lateral rectus resection, 90% were acceptably aligned at the 6-month postoperative exam. Among those patients undergoing a medial rectus resection, 95.2% obtained a successful result. CONCLUSIONS: A unilateral resection of the medial or lateral rectus is an effective tool in the treatment of undercorrected or recurrent strabismus. It is predictable, stable in the immediate postoperative period, and limits surgery to 1 eye. PMID- 11759774 TI - Surgical correction of congenital epiblepharon: low eyelid crease reforming technique. PMID- 11759775 TI - Giant cemento-ossifying fibroma of the maxilla causing proptosis in a young patient. PMID- 11759776 TI - Extraocular muscle and facial paresis in herpes zoster ophthalmicus. PMID- 11759777 TI - Increasing hyperopia and esotropia as the presenting signs of bilateral diffuse choroidal hemangiomas in a patient with Sturge-Weber syndrome. PMID- 11759778 TI - American women and health disparities. PMID- 11759779 TI - Understanding and eliminating racial inequalities in women's health in the United States: the role of the weathering conceptual framework. AB - I emphasize 3 features of racial inequality in women's health: It is greatest during young and middle adulthood; in some instances its severity is far greater than national comparisons suggest; and excessive levels of chronic morbidity and disability are widespread among African-American women, regardless of socioeconomic position. I propose that the weathering framework better captures these aspects of health inequality than do developmental models or those that focus on the role of poverty or individual unhealthy behaviors alone. Instead, weathering suggests that African-American women experience early health deterioration as a consequence of the cumulative impact of repeated experience with social, economic, or political exclusion. This includes the physical cost of engaging actively to address structural barriers to achievement and well-being. The weathering framework can be applied to research, to clinical and public health practice, and to social policy and political action. PMID- 11759780 TI - Frameworks matter: ecosocial and health and human rights perspectives on disparities in women's health--the case of tuberculosis. AB - Frameworks matter. To understand, intervene in, and improve the health of girls and women requires more than just good intentions and an eclectic list of "risk factors" or policy prescriptions, even if dressed up in notions of "gender." In this article, we present two frameworks-ecosocial and health and human rights that, if considered singly and in combination, we believe could prove useful to furthering work on understanding and addressing societal patterns of health, disease, and well-being. After explicitly summarizing our theoretical stances, we sketch the kinds of questions these frameworks invite us to consider, with reference to a particular case example: women and tuberculosis. By taking on the challenge of articulating and applying our frameworks, separately and in relation to each other, we hope to deepen understanding and generate new ideas that can make a difference for the health of girls and women. PMID- 11759781 TI - Social context, stressors, and disparities in women's health. AB - OBJECTIVE: to describe stressors experienced by women living in an economically disenfranchised urban community and test the relationships between those stressors and women's self-reported health status. METHODS: We used a stress process framework to examine the implications of economic divestment and race based residential segregation on the lives and health of women raising children in Detroit. We conducted qualitative analysis of in-depth interviews with 48 community residents and surveyed 679 women raising children in this community. Regression models controlling for age, education, and income examined the relationships of each of these stressors to symptoms of depression and general health status. RESULTS: Stressors described by women in the in-depth interviews included financial, work, family, safety, police and other municipal services, and disrespect or unfair treatment. Financial, police, and safety stress and unfair treatment were significantly associated with symptoms of depression; financial and family stress were significantly associated with self-reported general health status. CONCLUSION: Our results support the hypothesis that life stressors associated with economic divestment contribute to the disproportionate burden of disease experienced by African-American women residing in urban communities. Efforts to address racial and socioeconomic disparities in women's health should include policies that support economic development and municipal infrastructure as fundamental to the maintenance of health. PMID- 11759782 TI - Sex differences in the referral process for invasive cardiac procedures. AB - Nearly twice as many women in the United States die of heart disease and stroke every year as die from all types of cancer. Several studies have shown that women are less likely than men to be referred for invasive cardiac procedures. Despite extensive literature documenting sex differences in invasive cardiac procedure use, few studies have investigated the ways in which sex may affect the patient and physician decision-making process in referrals for cardiac care. This paper presents a framework outlining 8 stages of the referral process and discusses the role sex plays in each one. This framework was adapted from one describing the influence of race on the referral process for invasive cardiac procedures. A representative sample of the literature is reviewed to describe the influence of sex at each stage. PMID- 11759783 TI - Health disparities among older women: identifying opportunities to improve quality of care and functional health outcomes. AB - Older women experience a high burden of chronic illness, disability, and comorbidity, and this burden is highest among socioeconomically disadvantaged and minority women. The consequences of a mismatch between the organization, delivery, and financing of health care for older women and their actual needs fall disproportionately on low-income and minority women. New sources of data, such as the Medicare Health Outcomes Survey, a new quality measure for Medicare+Choice plans, will provide valuable information to practitioners about the health and functioning of older women in general and about socioeconomically disadvantaged and minority women in particular. This information can be used to develop and implement interventions to improve the quality and outcomes of care for vulnerable subgroups of older women. There is cause for optimism that by improving the quality of clinical preventive services and the management of common chronic conditions and geriatric syndromes it will be possible to improve functional health outcomes, prevent or postpone disability, and extend active life expectancy for all older women while making progress toward eliminating health disparities among the most disadvantaged. PMID- 11759784 TI - Reducing risk for cardiovascular disease in uninsured women: combined results from two WISEWOMAN projects. AB - OBJECTIVE: to evaluate the effectiveness of a cardiovascular disease (CVD) risk factor reduction program for financially disadvantaged women. The program included cholesterol and blood pressure assessments and tailored physical activity and nutrition interventions. METHODS: Women who attended selected National Breast and Cervical Cancer Early Detection Program sites in North Carolina and Massachusetts received either enhanced physical activity and nutrition interventions (EI) or minimum interventions (MI). The effectiveness of EI was assessed by pooling data from the North Carolina and Massachusetts projects after 1 year, and a mixed models analysis of covariance was used to compare changes in CVD risk factors across groups. RESULTS: The blood pressure, total cholesterol, and high-density lipoprotein cholesterol profiles of both groups improved, body weight was maintained, and smoking declined. The 10-year estimated coronary heart disease death rate (per 1,000 women) at baseline was 64.8 for the El group and 61.9 for the MI group. The rate declined by 3.5 deaths per 1,000 for the EI and 0.7 per 1,000 for the MI. Although the decline was statistically significant for the EI group, the difference between groups was not significant. CONCLUSION: Further lifestyle intervention research targeting financially disadvantaged women is needed. PMID- 11759785 TI - Inreach and outreach interventions to improve mammography use. AB - OBJECTIVE: to assess the effectiveness of patient-targeted interventions in increasing mammography use when performed outside (outreach) or inside the primary care medical setting (inreach). METHODS: We performed a meta-analysis of controlled interventions to increase mammography use in patients in the United States published between 1980 and February 2001. Interventions were classified by setting (inreach or outreach), mechanism of action (behavioral, cognitive, sociologic, or a combination), type of control group (active or usual care), number of strategies, and mode of delivery (static or interactive). Summary estimates were calculated with DerSimonian and Laird random effects models for each group of interventions. RESULTS: We included 66 studies with 98 separate interventions. Inreach and outreach interventions were equally effective in increasing mammography use. Compared to active controls, behavioral interventions with multiple strategies increased mammography use by 14.0% (95% CI, 8.7-19.2) in inreach and 18.7% (95% CI, 4.9-32.4) in outreach settings. Theory-based educational strategies delivered interactively increased mammography use by 10.7% (95% CI, 6.8-14.7) and 19.9% (95% CI, 10.6-29.1) in inreach and outreach settings, respectively. Interventions that combined behavioral and theory-based educational strategies with usual care controls increased mammography use by 14.0% (95% CI, 7.9-20.2) in inreach and 27.3% (95% CI, 14.7-40.0) in outreach settings. Finally, sociologic interventions increased mammography use by 10.7% (95% CI, 3.4-18.0) and 9.1% (95% CI, 1.7-13.3) in inreach and outreach settings, respectively. CONCLUSIONS: Inreach and outreach interventions to increase mammography use were similarly effective within intervention categories based on mechanism of action, mode of delivery, and type of control group. Ultimate decisions about intervention strategies will depend on the characteristics of the target population, practical considerations, and relative cost-effectiveness. PMID- 11759786 TI - Developing a video intervention to model effective patient-physician communication and health-related decision-making skills for a multiethnic audience. AB - The ENDOW study is a multisite, community-based project designed to improve decision-making and patient-physician communication skills for midlife African American, white, and Hispanic women facing decisions about hysterectomy. Based on results of initial focus groups, a patient education video was developed in English and Spanish to serve as the centerpiece of various interventions. The video uses community women to model appropriate decision-making and patient physician communication skills. Women in the target populations rated the video as useful to very useful and would recommend it to others. The use of theory driven approaches and pilot testing of draft products resulted in the production of a well-accepted, useful video suitable for diverse populations in intervention sites in several states. PMID- 11759787 TI - A public health framework for addressing black and white disparities in preterm delivery. AB - The Healthy People 2010 objectives call for the elimination of racial disparities in health, along with reductions in several multifactorial perinatal outcomes. Evidence-based interventions have been the focus of discussion to date. We propose a 6-component framework based on knowledge from the social, medical, psychological, and epidemiological literatures to guide development of interventions to reduce preterm delivery and eliminate disparities. Pilot testing and rigorous evaluation of the interventions developed from this framework are encouraged. PMID- 11759788 TI - Obesity and gestational diabetes among African-American women and Latinas in Detroit: implications for disparities in women's health. AB - OBJECTIVE: to estimate the prevalence of gestational diabetes mellitus (GDM), obesity, and excessive weight gain during pregnancy among Latinas and African American women in a large Detroit health system and explore risk factors associated with GDM and its implications. METHODS: Descriptive statistics, chi2 tests, analysis of variance, and logistic regression analyses were used to describe the prevalence of obesity, excessive pregnancy weight gain, and GDM and to assess factors associated with GDM risk in a cohort of 552 African-American women and 653 Latinas in a large Detroit health system. RESULTS: Women ranged in age from 14 to 47 years. Almost 47% of African-American women and 37% of Latinas were overweight or obese, and 53% of African-American women and 38% of Latinas gained excessive weight during pregnancy. The prevalence of GDM was 5.4% among Latinas and 3.9% among African-American women. After adjusting for other risk factors, Latinas were 2.5 times more likely than African Americans to develop GDM. Other independent risk factors were family history of diabetes, age, body mass index, and gestational weight gain before 28 weeks. CONCLUSION: Because most women have repeated contact with the health care system during and immediately after pregnancy, care providers have unique opportunities to identify and assist those who are at risk of obesity and diabetes. PMID- 11759789 TI - How do socioeconomic factors affect disparities in maternal mortality? AB - Socioeconomic factors affect nearly every cause of death, but not always in the same ways. Understanding which components of socioeconomic development were responsible for the great declines in maternal mortality in the United States and Britain can help us design effective programs in developing countries. The literature shows that maternal mortality is most strongly influenced by women's access to medical care for complications of pregnancy. In addition to international disparities in maternal mortality, there are still great disparities among racial groups in the United States. Here, too, analysis of the factors at work may be helpful in tailoring interventions. PMID- 11759790 TI - Maternal mortality: clinical implications of international perspectives. AB - Although the root causes of maternal mortality (MM) in nonindustrialized nations differ from those in the United States, some approaches to improving MM may be universal. Access to care is an issue in the United States aswell as internationally. There are many steps providers can take to improve access, from reducing language an cultural barriers, to taking adequate histories, to addressing such chronic conditions as obesity, diabetes, an hypertension before conception. When providers obtain adequate information before or during pregnancy, they can assess patient risk, plan educational and medical interventions, and introduce preventive measures that can reduce MM-in both the United States and the developing world. PMID- 11759791 TI - Barriers to preventing human immunodeficiency virus in women: experiences from KwaZulu-Natal, South Africa. AB - OBJECTIVE: to determine barriers to the adoption of safer sex practices in women in KwaZulu-Natal, South Africa. METHODS: This cross-sectional survey was conducted in a peri-urban and a rural community in 1991 to 1993. A structured, pretested questionnaire was administered to consenting women age 15 to 44 years who had been drawn randomly from a 10% systematic sample of households. The questionnaire included the following items: demographic characteristics, sexual relationships, knowledge of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), perception of risk, knowledge of and skills with respect to safer sex practices, and perceptions of rights to safer sex practices. RESULTS: A total of 219 interviews were conducted. Most respondents had an average of 8 years of schooling and were seeking employment. The majority of the respondents were sexually active (88.1%) and had extensive knowledge of modes of transmission and methods of preventing HIV/AIDS. Although most respondents underestimated their risk of HIV infection, a key reason for women not acting on their knowledge and perception of risk was that many did not believe they had a right to refuse sex with their partners (48.8%) or insist on condom use (46.1%). Most women thought their partners had a right to multiple partners (62.2%). Only 35.2% of respondents had the skills to object to their partners' having multiple partners, and 82.4% lacked the skills to use condoms. CONCLUSION: Women in these communities are at high risk of HIV infection. Their perceived lack of a right to safer sex, lack of skills to adopt safer sex practices, financial dependence on their sex partners, and the threat of violence influenced their ability to reduce their risk of HIV infection. PMID- 11759792 TI - Office of Women's Health, Food and Drug Administration: future directions for women's health. AB - The Office of Women's Health serves as an advocate for women's health throughout the Food and Drug Administration (FDA). Through and policies, the Office supports research in gender-related issues in the regulation and use of drugs, devices, biologics, and foods; initiates outreach and disseminates health information to women; provides leadership in increasing the number of women and appropriate data analysis in all phases of clinical trials; and promotes women's health in FDA actions. This article summarizes current activities and future directions in women's health at the FDA. PMID- 11759793 TI - Physical and mental health status of American grandparents providing extensive child care to their grandchildren. AB - OBJECTIVE: to compare the physical, mental, and functional health status of grandparents providing extensive care to grandchildren (30+ hours per week or 90+ nights per year) with that of custodial grandparents, noncaregivers, and two categories of less intensive care providers. METHODS: Data on a subsample of 3260 respondents to the National Survey of Families and Households who reported being grandparents during the 1992 to 1994 interviews were analyzed. Chi-square tests, 1-way ANOVAs, and multiple regression analyses compared self-reported functional health limitations, depressive symptoms, and change in self-reported health status and depression for extensive caregivers (223), custodial grandparents (173), and 3 other types of grandparents providing less or no child care. RESULTS: Extensive caregivers had levels of depressive symptoms comparable to those of custodial caregivers and significantly higher than those of noncaregivers and less intense care providers. One in 5 extensive caregivers had clinically relevant levels of depressive symptoms. Two out of every 5 extensive caregivers had at least 1 limitation in activities of daily living. CONCLUSIONS: Providing extensive care for a grandchild was associated with elevated levels of depression. Physicians should be alert to family role changes and symptoms of depression in their older patients. PMID- 11759794 TI - Elasticity of the anterior abdominal wall and impact for reparation of incisional hernias using mesh implants. AB - Mesh implantation to repair incisional hernia involves extensive disturbance of the integrity of the abdominal wall. To define the physiological requirements, we measured the elasticity of the abdominal wall of 14 anatomic samples. The complete abdominal wall was excised and stretched at a strain of 0-24 N in horizontal, vertical and oblique (upper and lower abdomen) directions. The resulting mean distension at 16 N was in the range between 11% and 32% for all directions. Furthermore, we found significant differences between tissue samples from male and female subjects, as well as considerable inter-individual differences in each group. Textile analysis of common mesh materials at 16 N showed elasticities in the range of 4%-16%. Comparing the textile characteristics with the physiological elasticity revealed inadequate properties in at least some of the mesh materials. Our findings indicate that the flexibility of the abdominal wall must be more or less restricted by extensive implantation of large meshes and recurrences may possibly be provoked at the margins of implanted materials. PMID- 11759795 TI - The importance of the size of Hessert's triangle in the etiology of inguinal hernia. AB - The aim of this study was to compare the inguinal area, known as "Hessert's triangle", in patients undergoing surgical treatment for inguinal hernia with the area in fresh cadavers without hernia. The 73 cadavers, which were not fixed in formalin, were examined within 15 h post mortem. A total of 132 measurements were made in these cadavers and compared with 130 measurements in 115 hernia patients. The average age was 44.2 years for patients and 32.7 years for cadavers. The mean height and weight were 1.68 m and 69.9 kg for hernia patients and 1.67 m and 70.0 kg for the cadavers, respectively. The mean area of Hessert's triangle was 8.97 cm2 (range 2.28-29.62 cm2) in the hernia patients and 2.95 cm2 (range 1.37-5.92 cm2) in the cadavers. This difference was statistically significant (P < 0.00). A larger triangle is created by a higher intersections of the internal oblique and transversus muscles and its aponeurosis to the rectus sheath. When these muscles contract, they move toward the inguinal ligament to occlude the triangle, but with a larger triangle, the occlusion is incomplete. Our anatomical measurements verified that the size of Hessert's triangle is an important factor in the etiology of inguinal hernia. PMID- 11759796 TI - Repair of giant hernias using more prosthesis. AB - Giant incisional hernias with total loss of substance are an ominous pathological condition characterized by massive depletion of muscular and fascial tissue, by complete loss of the anatomical and physiological function of the abdominal wall and by severe respiratory and visceral involvement. Over a 10-year period we operated 270 patients with voluminous incisional hernias, 12 of which had a total loss of substance. There was no intraoperative mortality. One patient died of myocardial infarction on the fifth and one died of intestinal occlusion and peritonitis the 11th postoperative day. Early postoperative complications occurred in only one patient who had skin necrosis with an infection at the polypropylene mesh. This was successfully treated with systemic antibiotic therapy and topical medication of the wound. There was also one minor recurrence over the pubis 1 year after the operation that required a new operation to replace the mesh. No respiratory complications occurred and all patients were normally active. The good results reported in our series encourage us to continue in this direction even though these patients are at high risk. PMID- 11759797 TI - Inguinal tensile strength and pain level after Shouldice repair. AB - BACKGROUND: Tension of the abdominal wall in the inguinal region induced by Shouldice repair of an inguinal hernia is said to be responsible for elevated postoperative pain levels. PATIENTS AND METHODS: In 20 patients we recorded the inguinal tensile strength during closure of the hernial gap using a wound retractor equipped with strain gauges. Postoperative pain levels were scaled using a visual analogous score, and correlated with the tensile strength of the inguinal abdominal wall together with peak flow and forced expiratory volume in 1 s (FEV1) 8, 24, and 48 h after the time of operation. RESULTS: Shouldice repair caused an average increase in inguinal tensile strength of 2.9 +/- 0.58 N (mean +/- SEM). The pain level expressed by active patients was twice the value obtained from resting patients (41.55 +/- 6.3% vs 20.81 +/- 7.1% 8 h after operation), but decreased slightly later on. Peak flow during forced expiration was depressed to about 80% of the control values, whereas the 1-s volume during forced expiration decreased only to 95% of the control value. We excluded any correlation between the recorded individual inguinal tensile strength or the changes in distance between the lateral edge of the rectus sheath and the base of the inguinal ligament and the postoperative pain level. CONCLUSION: We failed to see any evidence for the hypothesis that higher inguinal tensile strength induced by Shouldice repair leads to an elevated level of postoperative pain. If there is any effect, it may be masked by other factors with a stronger influence. PMID- 11759798 TI - Complications associated with the plug-and-patch method of inguinal herniorrhaphy. AB - The inguinal hernia continues to challenge general surgeons as evidenced by the variety of new surgical techniques developed to treat this malady. The persistence of recurrence rates ranging from 0.5% to as high as 20% provides the impetus to find the "best" repair. Surgeons continue to pursue an easy approach to this condition that will provide minimal patient discomfort and low to absent recurrence rates. Open tension-free and laparoscopic repairs have been shown to produce less discomfort and lower recurrence rates than conventional repairs under tension. Some of these repairs are relatively complex and difficult to learn. The use of laparoscopy can add a significant cost to the repair. Rutkow and Robbins described a tension-free technique in 1993 that promised minimal dissection, rapid return to regular activities and low recurrence rates. The plug and-patch repair has become a very popular method of herniorrhaphy. It is a quick procedure that is relatively easily learned. Since the initial description of the procedure, there have been anecdotal reports in the surgical literature describing an occasional interesting complication of this repair. There have been no comprehensive reviews of these occurrences. It appears that there are a significant number of patients who experience prolonged pain after this operation. Additionally, this plug often will shrink to a degree that results in a recurrence of the hernia. The most important finding of this study is that, as with other surgical procedures, attention to detail must be made to mitigate against adverse events. PMID- 11759799 TI - Seroma after laparoscopic repair of hernia with PTFE patch: is it really a complication? AB - We evaluated the true incidence of seroma formation after laparoscopic repair of incisional hernia with polytetrafluoroethylene (PTFE) patch. In a prospective study, 20 patients who underwent laparoscopic repair of incisional hernia with PTFE were evaluated clinically and with ultrasound examination for seroma formation up to the 90th postoperative day. Seroma was diagnosed clinically in only 35% of cases, while ultrasound examination revealed the presence of seroma in 100% of patients. Ultrasound examination is a reliable tool for diagnosis of early or delayed postoperative seroma formation following laparoscopic repair of incisional hernia with Gore-Tex Dualmesh. PMID- 11759800 TI - Functional impairment and complaints following incisional hernia repair with different polypropylene meshes. AB - The influence of mesh material on the clinical outcome of hernia repair has often been neglected, although recent studies have clearly demonstrated the importance of mesh properties for integration in the abdominal wall. Of particular significance are the amount of mesh material and the pore size. In the following study, patients received different mesh types with distinct amounts of polypropylene and of various pore sizes for incisional hernia repair. We investigated whether the type of material influenced the clinical and functional outcomes. Between 1991 and 1999, 235 patients received polypropylene meshes in a sublay position for incisional hernia repair: 115 patients were implanted with a Marlex heavy-weight mesh (Mhw mesh), 37 patients with an Atrium heavy-weight mesh (Ahw mesh) and 83 with a Vypro low-weight mesh (Vlw mesh). The study protocol included ultrasound examination and 3D-stereography in all patients, with a total follow-up of 24 +/- 13 months (Mhw-mesh), 11 +/- 8 months (Ahw-mesh) and 8 +/- 7 months (Vlw-mesh). Our findings demonstrate that the side effects of mesh implantation, comprising paraesthesia and restriction of abdominal wall mobility, were significantly affected by the type of material implanted. Three-dimensional stereographic examinations were well in accordance with our clinical findings. Our data support the hypothesis that the use of low-weight large-pore meshes is advantageous for abdominal wall function. PMID- 11759801 TI - Antibiotic prophylaxis in incisional hernia repair using a prosthesis. AB - Antibiotic prophylaxis in clean surgery with implantation of prosthetic material is widely accepted, although there are no studies on its use in abdominal incisional hernia repair. The objective was to evaluate antibiotic chemoprophylaxis in incisional herniorrhaphy with the implantation of prosthetic material. A prospective non-randomized study (1990-1998) was conducted to analyse 216 patients undergoing surgery for abdominal incisional hernia who required a prosthesis (polypropylene) in the reconstruction and who met the criteria for clean surgery. Risk factors were observed in 31.5%, the most frequent being diabetes and obesity. The incisional hernia was located mostly in the abdominal midline and in 64.4% measured over 10 cm. Antibiotic prophylaxis was administered in 140 patients (64.8%) via the systemic route, the antibiotics being first- or second-generation cephalosporins or amoxicillin-clavulanic acid. Surgical wound infection occurred in 39 patients (18.1%), 19 who had received antibiotic prophylaxis (13.6%) and 20 who had not (26.3%). In multivariate analysis using logistic regression, the variables with statistical significance for local septic infection were antibiotic prophylaxis and number of risk factors. We can conclude therefore that antibiotic chemoprophylaxis is useful in abdominal incisional herniorrhaphy surgery with implantation of prosthetic material for reducing local septic complications. PMID- 11759802 TI - Mesh repair of a pelvic bone defect caused by a migrated acetabular cup. AB - Conventional transacetabular removal of the migrated acetabular cup can be hazardous due to intraoperative injury to iliac vessels. We present a case of a migrated acetabular cup, in which we used a combined preperitoneal and acetabular approach for its removal. With a bimanual approach, the procedure was safer and easier and allowed mesh repair of the pelvic bone defect. The preperitoneal mesh repair is a well-known method for inguinofemoral hernias. However, it has not been used before in the repair of an acetabular defect after removal of a migrated cup. PMID- 11759803 TI - Sliding appendiceal inguinal hernia with a congenital fibrovascular band connecting the appendix vermiformis to the right testis. AB - It is not uncommon to find the appendix vermiformis within a hernia sac; however, sliding appendiceal inguinal hernia is rare. A 9-month-old boy with an incarcerated right scrotal hernia is presented in this case report. Although the hernia was reduced through a conservative approach, appendix vermiformis remained in the hernia sac because of its attachment to the upper pole of the right testis. Exploratory surgery during the inguinal hernia repair revealed a connecting band that extended from the appendix vermiformis into the scrotum and attached to the right testicle. Histologic examination showed that the band was congenital. After reduction of an incarcerated hernia, the persistence of a thickened or a cord-like structure is a warning for the presence of a sliding hernia. We suggest that this uncommon developmental anomaly is likely to cause the processus vaginalis to remain patent, thus facilitating hernia formation. PMID- 11759804 TI - Traumatic diaphragmatic hernia presenting as a tension fecopneumothorax. AB - Diaphragmatic injury with accompanying hernia is a well-documented complication associated with both penetrating and blunt trauma. It occurs in approximately 3% of abdominal injuries with a 2:1 ratio of penetrating to blunt trauma. Diagnosis requires a high index of suspicion since diaphragmatic injury can only reliably be ruled out by direct visualization, i.e., laparoscopy. Hence, delayed presentation with complications secondary to the injury is not uncommon. We discuss a case of a young man who presented in respiratory distress six years after a stab wound to the left chest. The patient was hypoxic, with a chest X-ray (CXR) demonstrating a pneumothorax with effusion. A chest tube was placed with a rush of air and foul-smelling purulent drainage. Work-up revealed incarcerated transverse colon in a diaphragmatic hernia. Celiotomy demonstrated necrotic colon in the chest with gross fecal contamination in both the chest and abdomen. The diaphragmatic defect was closed and a Hartmann's procedure performed. The patient did well postoperatively except for the development of an empyema, which resolved with conservative management. Our patient is the eleventh reported case of a tension fecopneumothorax resulting from traumatic diaphragmatic herniation. This paper reviews all cases including the diagnostic work-up, operative approach, and ex ected postoperative course of this unusual condition. PMID- 11759805 TI - Obturator hernia: the plug technique. AB - The obturator hernia is an uncommon condition, with clinical manifestations of pain and intestinal obstruction. The preoperative diagnosis is difficult. The treatment is always surgical. There are several repair techniques that have been described: sac ligation alone, direct suture repair, use of autologous tissue or prosthetic repair. We report a case of an obturator hernia that was treated by the use of a plug of Mersilene. PMID- 11759806 TI - Central mesh recurrence after incisional hernia repair with Marlex--are the meshes strong enough? AB - The use of biomaterial meshes in the repair of incisional abdominal wall hernias is now widely accepted internationally. The introduction of synthetic meshes to achieve tension-free repair has led to a satisfactory reduction in the recurrence rate to less than 10%. However, the use of such biomaterials can result in the occurrence of undesirable complications such as increased risk of infection, seromas, restriction of the abdominal wall and failure caused by mesh shrinkage. Additionally, at the time of writing there is much discussion concerning the potential risk of a persistent foreign body reaction directly associated with the meshes with regard to possible malignant transformation. As such, the trend seems to be toward the use of lighter meshes utilizing less non-absorbable material. One particular novel mesh theoretically capable of guaranteeing the necessary mechanical stability uses 70% less biomaterial. Against this background, we report a central mesh recurrence through the mesh following incisional hernia repair with a Marlex mesh. To our knowledge, this is the first description of a central mesh recurrence, and we discuss a possible mechanism with particular emphasis on the required abdominal wall forces both physiologically and after incisional hernia repair. PMID- 11759807 TI - Chorion laeve trophoblasts of preeclamptic fetal membranes: histochemically detectable enzyme activities do not change at a subcellular level. AB - We examined the subcellular localization of ADP-degrading activity and cytochrome c oxidase (CCO) activity in chorion laeve trophoblasts from term and near term human fetal membranes, and compared them with those from severe preeclamptic fetal membranes. The methods used for the detection of enzyme activities were the lead nitrate method for ADP-degrading activity and the diaminobenzidine method for CCO. Precipitates indicative of ADP-degrading activity were visible on surface microvillous plasma membranes of chorion laeve trophoblasts both from normal and preeclamptic fetal membranes. The intensity and distribution patterns were the same in the normal and preeclamptic subjects. CCO labeling was visible in almost all laeve trophoblastic mitochondria both in normal and preeclamptic cases. Previously, we demonstrated that in preeclamptic villous trophoblasts there were decreases in ADP-degrading activity and the presence of CCO-negative mitochondria, which were proposed to lead to dysfunction of each villous trophoblast, and finally to placental insufficiency in preeclampsia. Reductions or changes in enzyme intensities/distribution patterns, which are characteristic features of preeclamptic villous trophoblasts, were absent in chorion laeve trophoblasts in preeclampsia. These results suggest that in preeclampsia there are no, or at least less severe, abnormalities in the enzyme activities of chorion laeve trophoblasts, compared with villous trophoblasts, as far as enzyme histochemically detectable enzymes are concerned. PMID- 11759808 TI - Granulocyte macrophage colony stimulating factor (GM-CSF) biological actions on human dermal fibroblasts. AB - Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GM-CSFR) on human normal skin fibroblasts from healthy subjects (NFPC) and on a human normal fibroblast cell line (NHDF) and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GM-CSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM) components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC) is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF) cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such "differentiation" is an important event induced by such cytokine. PMID- 11759809 TI - Relationships between neuronal cell adhesion molecule and LHRH neurons in the urodele brain: a developmental immunohistochemical study. AB - Polysialic acid (PSA), a homopolymer attached to neural cell adhesion molecule (NCAM) is considered a major hallmark of vertebrate cell migration. We studied the distribution of PSA-NCAM by immunohistochemistry, during brain development, in two urodele amphibians, Pleurodeles waltl and the neotenic newt Ambystoma mexicanum. In both species a gradual increase of immunolabelling was observed throughout the brain from developmental stage 30 to stage 52. At the onset of metamorphosis, some differences became evident: in Pleurodeles immunostaining was gradually restricted to the olfactory system while in Ambystoma, PSA-NCAM maintained a more extended distribution (for example throughout the telencephalic walls) suggesting, for the brain of this latter species, a rather preserved neuronal plasticity. The aim of the present work was to correlate the above described PSA-NCAM-immunoreactivity (IR) with the distribution of luteinizing hormone-releasing hormone (LH-RH) containing neurons, which represent a well known example of neural elements migrating from the olfactory placode. LHRH-IR, undetectable till stage 30, was later found together with PSA-NCAM-IR in both the olfactory system and septo-hypothalamic areas. Such observations further support a role of PSA in providing a migration route toward the establishment of a part, at least, of the urodele LHRH system. The possible functional meaning of the LHRH containing neurons localized between dorsal and ventral thalamus of Ambystoma, never reported before in this area, almost devoid of PSA-NCAM-IR, is discussed. PMID- 11759810 TI - Comparative analysis of NADPH-diaphorase positive neurons in the rat, rabbit and pheasant thoracic spinal cord. A histochemical study. AB - The distribution of NADPH-diaphorase (NADPH-d) activity was investigated and compared in the rat, rabbit and pheasant thoracic spinal cord. The investigation of all spinal cord regions (laminae) in three experimental species revealed marked differences in the distribution of NADPH-d activity. Cross sectional analysis of the spinal cord of the rat, rabbit and pheasant confirmed differences in the shape of the gray matter in all examined species. More detailed investigation of Rexed's laminas showed similar distribution of NADPH-d activity in the spinal cord of the rat and rabbit, which were different when compared with the spinal cord of the pheasant. Ventral horn of the rat and rabbit showed no labelling whereas in pheasant this area possessed a number of scattered, intensively stained neurons. In the location of autonomic preganglionic neurons, differences were found as well. In the rat there was seen a number of densely packed, clearly dark blue coloured neurons. Similarly, these neurons were present in the rabbit spinal cord but they were less numerous. No staining was found in this region of pheasant. Pericentral area (lamina X) and intermediate zone (laminaVII) revealed the presence of NADPH-d positive neurons in all examined species although they differed in number and shape of their bodies. The dorsal horn showed the presence of NADPH-d staining in all three animals but its distribution was different in medio-lateral direction. It can be suggested that observed differencies in the presence and distribution of NADPH-d activity across the examined species may reflect different fylogenetic development. PMID- 11759811 TI - Ultrastructural and immunocytochemical characterization of interstitial cells in pre- and postnatal developing sheep pineal gland. AB - Pineal gland interstitial cells from 32 sheep embryos (from day 54 of gestation until birth) and 18 sheep (from 1 month to >2 years) were analysed using ultrastructural and immunohistochemical techniques. From day 98 of gestation and throughout postnatal development, a second cell type was observed in addition to pinealocytes; these cells displayed uniform ultrastructural features similar to those of CNS astrocytes. Ultrastructural homogeneity was not matched by the results of histochemical and immunohistochemical analysis. Expression of phosphotungstic acid hematoxylin, glial fibrillary acidic protein and vimentin indicates that the second cell population in the developing ovine pineal gland is, in fact, a combination of glial-astrocyte cells at varying stages of maturity. Pineal interstitial cells started to show signs of functional activity evident in vascular tropism; such activity, evident from around day 98 of gestation, appeared to relate to the exchange of substances between the pineal parenchyma and blood vessels and, though it continued throughout postnatal development, was most evident in animals slaughtered between 9 months and 2 years of age (group II). Morphologically, functional activity in interstitial cells in this age-group was apparent in: 1, formation of specific contact sites between interstitial cells and nerve fibres in the perivascular space; and 2, the presence of numerous gap junctions between the bulbous endings of cytoplasmic processes. PMID- 11759812 TI - Morpho-histochemical changes in the liver and intestine of young giltheads (fish nursery), Sparus aurata, L., induced by acute action of the anionic tensioactive alkylbenzene sulphonate. AB - In the present study we have assessed the effect on the survival and the morpho histochemical changes in the liver and intestine of young giltheads (fish nursery), Sparus aurata, L., induced by acute action of the anionic tensioactive, alkyl benzene sulphonate (ABS). Firstly, the LC50 of ABS at 96 hours was found to be 0.6 mg/L. Secondly, lots with 50 young giltheads (fish-nursery) were exposed to ABS concentrations of 0.5, 1, 3 and 5 mg/L, to obtain the surface tension value and exposure time required for 50% mortality of the specimens at each tested concentration. Exposure to ABS caused several forms of histopathological damage in the liver (the radial arrangement of hepatocytes was lost) and intestine (destruction of the structure of villi and increase in thickness of the other three layers). In addition, changes in bio-macromolecule components (proteins in general, siderophile proteins, neutral mucopolysaccharides, glycogen and acid mucopolysaccharides) were observed. The degree of these alterations was dependent upon the ABS concentration. These changes could have detrimental effects on the growth and survival of the species. PMID- 11759813 TI - Glyconjugates in epidermal, branchial and digestive mucous cells and gastric glands of gilthead sea bream, Sparus aurata, Senegal sole, Solea senegalensis and Siberian sturgeon, Acipenser baeri development. AB - Epidermal, branchial and digestive mucous cells, and the gastric glands of larvae/postlarvae (from hatching until 45 days posthatching) of three fish species (two teleostean and a chondrostean) were investigated using conventional histochemical methods (periodic acid schiff -PAS-, diastase-PAS; alcian blue pH 0.5, 1 and 2.5) in order to distinguish neutral and acidic (carboxylated and sulphated) glycoconjugates, as well as bromophenol blue reaction for identification of proteins. Additionally, the presence and distribution of sugar residues in the oligosaccharide side chains of glycoconjugates were investigated using horseradish peroxidase (HPR)-conjugated lectins (Con A, DBA, WGA and UEA I). Most mucous cells (digestive, epidermal and branchial) of Siberian sturgeon, Acipenser baeri, sea bream, Sparus aurata and Senegal sole, Solea senegalensis larvae were PAS- and alcian blue- (pH 2.5 and 0.5) positive, with small variations between organs/tissues and species. Bromophenol blue reaction (general proteins) was positive in a minority of the mucous cells, usually in those cells which were PAS-negative. Proteins rich in sulphydryl (-SH) and/or disulphide (-S S-) groups related with the glycoprotein nature of the glycoconjugates present in mucous cells were also observed. Epidermal, branchial and digestive mucous cells of all studied larvae did not contain glycogen or lipids. Con A lectin staining was negative in all mucous cells types of sea bream and sole, but oesophageal mucous cell of sturgeon were reactive to different lectin reactions, suggesting the presence of mannose -Man- and/or glucose -Glc-, L-fucose -Fuc- ; N-acetyl-D galactosamine -GalNAc-, as well as N-acetyl-D-glucosamine- GlcNAc - and/or sialic acid -NANA- residues. Digestive mucous cells of all studied larvae were positive to WGA and DBA lectins. Epidermal and branchial mucous cells of sea bream and sole were Con A, DBA and UEA-I unreactive. However, mucous cells of sturgeon larvae were stained with UEA-I lectin. Gastric glands appear very early in sturgeon stomach larvae development (between 5-6 days posthatching) but rather late (around 40 days) during the ontogeny of sole and sea bream larvae. These glands contain neutral glycoproteins with Man and/or Glc, Fuc, GlcNAc- and/or sialic acid and rich in GalNAc- sugar residues, as well as proteins moderately rich in arginine, and others particularly rich in tyrosine and tryptophan. PMID- 11759814 TI - A histological and histochemical study of the oesophagus and oesogaster of the Senegal sole, Solea senegalensis. AB - A histological and histochemical study was performed in the buccal cavity and papillae, which were around the teeth, as well as in the oesophagus and oesogaster of the Senegal sole, Solea senegalensis adult specimens. The oesophagus and oesogaster were made up of four distinct layers: mucosa, submucosa, muscular and serous. Two morphological types of epithelial cells were distinguishable in the oesophageal mucosa: the more numerous type cells possessed an electron-dense cytoplasm, whereas the cytoplasm was electron-clear in the other cells. Mucus-secreting cells were the dominant feature of the epithelium throughout the oesophagus. These goblet cells were filled with numerous mucous droplets of low electron-density. The oesophagus was devoid of taste buds. In the oesogaster mucosa, three types of cells were distinguished: dark, rodlet and light epithelial cells. Dark epithelial cells showed different characteristics from that in the oesophagus: the nucleus was irregular with an electron-dense hyaloplasm, the cytoplasm had a scarce smooth and granular endoplasmic reticulum; a Golgi apparatus consisted of four parallel cisternae, dense granules without membrane, lysosomes and numerous mitochondria. The rodlet cells were elongated, contained rod-like structures and were surrounded by an electron-dense capsule like structure. The bulk of the rodlet cell was composed of up to 20 extended rodlet units. Light epithelial cells of the oesogaster had the same characteristics as those observed in the oesophagus and contained numerous mitochondria with a dense matrix, abundant smooth endoplasmic reticulum and numerous vesicles. In the goblet cells of the papillae, sulfomucin was recognised, since they showed alcianophilia (alcian blue pH 1.0 and 0.5). These cells were negative to protein reaction (bromophenol blue) and contained -S-S- and SH groups. Enzymatic activities (alkaline phosphatase, acid phosphatase, ATPase (pH 7.2 and 9.4) and lipid reactions were negative in the goblet cells of the buccal cavity. Epithelial cells of oesophagus contained a weak presence of acid and neutral mucopolysaccharides. Oesophageal goblet cells contained carboxylated, sulphated (weakly and strongly ionised) mucosubstances and sialic acid. Most goblet cells did not contain proteins and presented disulphide (-S-S-) and sulphydril (-SH) groups. Proteins in general, and in particular those rich in lysine, tyrosine and arginine were present in the epithelium, lamina propria, submucosa and muscular layer of the oesophagus. Lipids in general and phospholipids were observed in the oesophageal epithelium while unsaturated, acid and neutral lipids were not observed. The lamina propria and submucosa contained a weak presence of phospholipids and unsaturated lipids. Acid phosphatase and ATPase (pH 7.2) activities were observed in the lamina propria, submucosa and muscular regions, while ATPase (pH 9.2) activity was weak in these areas. ATPase activity (pH 7.2 and 9.5) was very weak in the epithelium. Oesophageal goblet cells were negative to lipid and enzymatic reactions. PMID- 11759815 TI - Comparative study of enzymes in testes and ovaries from adult Dipetalogaster maximus (Uhler) and triatoma infestans (Klug) (Hemiptera: Reduviidae). correlation with fine structural organization. AB - Activities of hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), fructose-6-phosphate kinase (F6PK), glutamate dehydrogenase (GlutDH), aspartate aminotransferase (AAT), malate dehydrogenase (MDH) and glycerol-3-phosphate dehydrogenase (GPDH) were determined in tissue extracts of testes and ovaries of adult Dipetalogaster maximus (Uhler) and Triatoma infestans (Klug) (Hemiptera: Reduviidae), insect vectors of Chagas disease. The fine structure organization of the same organs were studied by electron microscopy. Results allow the following inferences: in testes from both species, most of the glucose would be utilized through the glycolytic pathway. Amino acid catabolism for energy purposes appears to be unimportant. The number of mitochondria and the development of the rough endoplasmic reticulum in cells of the spermatogenic line indicate the occurrence of active oxidative metabolism and protein synthesis; in ovaries, levels of G6PDH indicate the existence of an active pentose pathway which would supply the NADPH required for fat and ecdysteroid synthesis. Amino acid catabolism appears to be relatively more important in ovary than in testis. Fat and glycogen are stored in follicular cells of D. maximus; oocytes of both species contain numerous fat droplets. Abundant mitocondria are present in follicular cells and oocytes. A well developed rough endoplasmic reticulum and free ribosomes are also conspicuous in these cells. The malate/aspartate H-transfer system seemed to be relatively more important than the glycerophosphate shuttle in ovaries as well in testes. PMID- 11759816 TI - Clinical management of women with genomic BRCA1 and BRCA2 mutations. AB - PURPOSE: There is increasing evidence that BRCA1 and BRCA2 associated tumors may differ from sporadic cancers. The purpose of this report is to review the current state of knowledge of BRCA1 and BRCA2, the biology of associated tumors, and possible risk reduction strategies in women with these deleterious mutations. DESIGN AND METHODS: We conducted an extensive literature search of all published articles (including Medline) on preclinical data on the function of BRCA1 and BRCA2, associated tumor pathology, and the clinical management for both unaffected carriers and affected patients. RESULTS: BRCA1 and BRCA2 are likely to act as tumor suppressor genes, and together with RAD51 operate in a common DNA damage response pathway implicated in double-strand repair. Breast cancers associated with BRCA1 are frequently of a higher grade, steroid hormone receptor negative, and appear to have a higher proportion of atypical or typical medullary subtype. Conversely, BRCA2 associated breast cancers do not differ significantly from sporadic cancers. No special tumor phenotype has been ascribed to BRCA1 or BRCA2 associated ovarian cancers. Guidelines for risk reduction strategies for the high risk unaffected carrier have been recommended by expert panels in the USA and Europe. Lifestyle changes, multi-modality screening, chemoprevention, and prophylactic oophorectomy and mastectomy, with their possible benefits and attendant risks are described. Finally, locoregional and systemic treatment in breast and ovarian cancers associated with these mutations, and differences between these and sporadic cancers are discussed. CONCLUSIONS: Although the incidence of breast or ovarian cancers that can be attributed to BRCAI or BRCA2 mutations account for less than 5% of all cancers, these cancers may differ from sporadic cases in terms of tumor biology and phenotype. These differences may impact directly on clinical management of breast and ovarian cancer patients, and their relatives. Further recommendations of these patients are constantly changing as new information emerges on the clinical behavior of these cancers. PMID- 11759817 TI - Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas. AB - The E2F family of transcription factors can induce both cell proliferation and apoptosis. Whether they function as oncogenes or tumor suppressors appears to be tissue specific. Their role in breast carcinogenesis remains unclear. We found a decreased expression of E2F-1 and E2F-4 in 70% (7/10) of primary breast carcinomas and in all (10/10) metastatic nodal tissues when compared with the corresponding normal breast tissue. No tumor-specific mutation was detected, but polymorphisms were identified in E2F-1 exon 5 and in the polyserine tract of E2F 4. The presence of polymorphisms did not correlate with E2F expression. Among the 12 human breast cancer cell lines, one contained a missense mutation in E2F-1 exon 2. Five (42%) cell lines overexpressed E2F-1, while three (25%) expressed low levels of the protein. Our results suggest that not only are the E2Fs likely to function as tumor suppressors in breast cancer, but also that their down regulation may be important in the development of metastases. PMID- 11759818 TI - Evaluation of different methods for the detection of minimal residual disease in blood and bone marrow of patients with primary breast cancer: importance for clinical use? AB - We studied cytokeratin-positive (CK+) cells in the bone marrow (BM) and tumor markers (TM) in the blood of 128 patients with primary breast cancer in order to obtain an early diagnosis of residual disease. CK+ cells of two BM aspirations were detected by immunocytochemistry (IC). To evaluate the usefulness of immunomagnetic separation (IMS) for tumor cell enrichment in clinical samples, IMS was performed prior to IC and compared with the results for IC alone. The overall CK+ rate was 34% (44/128 patients), 29% (15/51) for patients with T1 tumors, 33% (28/84) for N0 patients and 31% (26/82) for patients with G1-2 breast carcinoma. Interestingly, 67% of CK+ patients were only positive in one of the two aspirates studied. A comparison between IC alone and IMS/IC could be performed in 70/128 patients (28/70 CK+). In 6/28 patients, CK+ cells were detected by both methods, in 16/28 patients only by IC and in 6/28 patients only by IMS. At least one TM, including carcinoembryonic antigen, carbohydrate antigen 15-3 and tissue polypeptide antigen, was increased in 58/128 (45%) patients [21/58 (36%) were CK+ in the BM]. Surprisingly, levels for the extracellular domain of Her-2/neu in serum samples were within the normal range in every patient studied. After a 2-year follow-up, 7/128 patients relapsed (3/7 CK+/TM-; 2/7 CK-/TM+; 2/7 CK-/TM-). We conclude that studying two BM aspirates for CK+ cells by IC in combination with TM determination is useful for identifying patients with a higher risk for relapse, however, tumor cell enrichment techniques will have to be improved for clinical use. PMID- 11759819 TI - Early-stage breast cancer treatment among medically underserved women diagnosed in a national screening program, 1992-1995. AB - BACKGROUND: Little research has been conducted on the breast cancer treatment of low income, underserved women. This study was designed to describe initial treatment of breast cancer among low-income women diagnosed through federally funded screening programs in Detroit, Michigan, and the states of New Mexico and California; and to compare the treatment received by program women with early stage breast cancer with that of all women diagnosed in those regions. METHODS: Data from the three screening programs were linked with cancer registry data from the corresponding geographic areas. All women diagnosed between 1992 and 1995 through the state-based screening programs and all women contemporaneously diagnosed with breast cancer in the three regions were studied. Descriptive analyses were done of the proportion of women with breast cancer receiving treatment; the proportion of early-stage breast cancer (stage I or II) cases treated with breast-conserving surgery, and the proportion treated with mastectomy; and among women with breast-conserving surgery, the proportion receiving radiation therapy. Logistic regression models controlled for age and stage at diagnosis, race or ethnicity and geographic region. RESULTS: Less than 2% of program women diagnosed with breast cancer received no treatment. More than two of five women with early-stage breast cancer underwent breast-conserving surgery, with 72% of these women receiving radiation therapy. Multivariate regression analysis revealed that women with stage IIA or IIB breast cancer had lower odds of undergoing breast-conserving surgery than women with stage I (0.51 [95% CI = 0.30-0.87] and 0.36 [95% CI = 0.19-0.70], respectively). Women over age 65 and those with incompletely staged cancer had the lowest odds for receiving radiation therapy after breast-conserving surgery (0.29 [95% CI = 0.09-0.99] and 0.14 [95% CI = 0.03-0.72], respectively). Women diagnosed through the screening programs had odds of undergoing breast-conserving surgery similar to those of all women in the regions (1.11 [95% CI= 0.89-1.39]). CONCLUSIONS: Treatment patterns for women diagnosed with early-stage breast cancer through three state-based screening programs appear to have been similar to those reported in the literature. In addition, their treatment appears to have been similar to that of other women during the same time period. PMID- 11759820 TI - Accuracy of mammography and echography versus clinical palpation in the assessment of response to primary chemotherapy in breast cancer patients with operable disease. AB - The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0) submitted to primary chemotherapy. A low relationship was recorded between tumor size assessed clinically and that evaluated by either mammography: Spearman R = 0.38 or echography: R = 0.24, while a greater correlation was found between the tumor dimension obtained by the two imaging techniques (R = 0.62). According to the WHO criteria, the grade of response of breast cancer to primary chemotherapy, showed by mammography and echography, was less marked than the grade of response seen at clinical examination. Residual tumor size assessed clinically depicted a stronger correlation with pathological findings (R = 0.68) than the residual disease assessed by echography (R = 0.29) and mammography (R = 0.33). Post-chemotherapy histology evaluation revealed pathological complete response in three cases (2.1%). Two of these cases were judged as complete responders by clinical palpation but only one was recognized by mammography, and none by echography. Clinical response, but not the response obtained by the two imaging techniques, was a significant predictor for longer disease free survival (p = 0.04). To conclude, physical examination measurements remain the method of choice in evaluating preoperatively the disease response in trials of primary chemotherapy. Prediction of pathological outcome is not improved by echography and mammography. PMID- 11759821 TI - Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy. AB - This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12 Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods. PMID- 11759823 TI - Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women. AB - Serum levels of MUC1 and antibodies (Abs) against MUC1 (IgG and IgM-MUC1) were evaluated in healthy women related to pregnancy and lactation status. A total of 149 serum samples were obtained from: nulliparous, primiparous pregnant, multiparous pregnant that have lactated, multiparous pregnant without lactation, multiparous non-pregnant actual lactating, multiparous non-pregnant that have lactated and finally, multiparous non-pregnant women without lactation. In all assays, we included pre- and post-serum samples belonging to a breast cancer patient vaccinated with a MUC1 derived peptide. CASA test was employed to measure MUC1 while IgG- and IgM-MUC1 serum Abs were evaluated with an ELISA using a 100 mer peptide as catcher. In all groups, mean IgM levels were higher than IgG mean values; when samples were grouped in pregnants versus non-pregnants, a significant difference was detected with both Abs, being raised in non-pregnants. When samples were grouped in lactating versus non-lactating a significant difference was detected with IgG-MUC1, being raised in lactating women while no significant difference was found with IgM-MUC1. The evaluation of serum MUC1 levels confirmed previous results since a significant difference between pregnant versus non-pregnant groups was found while lactating versus non-lactating samples did not. CONCLUSIONS: (i) Increased MUC1 serum levels are apparently associated with pregnancy but not with lactation; (ii) MUC1 Abs are mainly associated with lactation and with non-pregnant status. These results may be considered a contribution on studies about protection against breast cancer induced by pregnancy and lactation. PMID- 11759822 TI - Adherence to recommendations for clinical follow-up after benign breast biopsy. AB - PURPOSE: Women who undergo a benign breast biopsy are at elevated risk for the subsequent development of breast cancer (BC). Therefore, appropriate clinical follow-up of a benign breast biopsy is important. The present study examines the extent and correlates of nonadherence with follow-up recommendations after a benign breast biopsy. METHODS: Women (n = 114) who had undergone a benign breast biopsy completed an initial telephone interview within 50 days of their biopsy (mean = 21 days). Additional telephone interviews were completed at 4 and 8 months post-biopsy. Measures of BC risk perception, general and BC-specific distress, BC-related attitudes and beliefs, social support, optimism, and informational coping style were completed. Specific recommendations for clinical follow-up and evidence of actual follow-up were obtained from medical records. RESULTS: Of 103 women given a specific recommendation for clinical follow-up, 34% were classified as nonadherent with follow-up recommendations. Logistic regression analyses indicated that nonadherent women were characterized by younger age, recommendations for follow-up by clinical breast examination alone, greater confidence in their ability to perform breast self-examination properly, higher perceived personal risk for BC, and greater BC-specific distress. CONCLUSION: Despite the importance of appropriate clinical follow-up of a benign breast biopsy, about one-third of women did not adhere to recommended follow-up. Risk factors for nonadherence suggest potential avenues for interventions to enhance participation in appropriate clinical follow-up. PMID- 11759824 TI - Immunohistochemical determination of HER2 expression in breast cancer from core biopsy specimens: a reliable predictor of HER2 status of the whole tumor. AB - HER2 overexpression in breast cancer is associated with a poor prognosis, resistance to endocrine therapy and chemosensitivity to anthracyclines and paclitaxel. Moreover, trastuzumab (Herceptin) shows therapeutic benefit in patients with HER2 overexpressing tumors. Therefore, knowledge of the pretherapeutical HER2 status allows an optimal selection of patients for treatment. In addition to a definitive histological diagnosis, core biopsies of tumors offer the opportunity to evaluate the HER2 status preoperatively. In 64 patients with invasive breast cancer, sections of core biopsies and of the subsequently removed whole tumor were investigated immuno-histochemically with the DAKO HercepTest. Fifteen tumors (23%) revealed HER2 overexpression, and 44 tumors (69%) were negative in both, the core biopsy and the whole tumor sections. Two core biopsies were negative whereas the corresponding final specimen was 2+ positive. In 3 cases weak overexpression was observed in the core biopsy, but the whole tumor was negative. The overall concordance of the results achieved at core biopsy and whole tumor sections was 92% (kappa = 0.8). A negative HER2 result on core biopsy was never associated with a score 3+ tumor specimen nor was there a case of negative whole tumor specimen with a preceding 3+ score in the biopsy. If one demands the highest degree of overexpression (3+), 100% of our study patients would have been selected correctly using the results on core biopsy alone. We thus conclude, that the immunohistochemical investigation of core biopsies offers the opportunity for a valid preoperative estimation of HER2 overexpression. PMID- 11759826 TI - Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells. AB - Epidemiological studies indicate that there is a positive correlation between alcohol consumption and the risk of breast cancer. Experimental results demonstrate that ethanol is a tumor promoter and chronic ethanol exposure enhances metastasis and growth of breast cancer. The present study used an in vitro model to investigate the molecular mechanism(s) underlying tumor promoting effects of ethanol. With differential display reverse transcription polymerase chain reaction, we demonstrated that human ribosomal large subunit protein L7a (rpL7a) was an ethanol-responsive factor in T47D breast cancer cells. The results of northern blot hybridization revealed that the effect of ethanol on L7a expression was duration- and concentration-dependent. Initial exposure resulted in a 2-fold increase in rpL7a level, whereas a longer exposure period produced a down-regulation. Ethanol had little effect on the stability of rpL7a mRNA; however, the transcription rate of rpL7a was significantly increased by ethanol. Ethanol-induced up-regulation of rpL7a was not a simple stress response, because other stress inducers, such as heat shock, did not affect the expression of rpL7a. Furthermore, breast cancer cells expressed higher level of rpL7a than normal mammary epithelial cells. Ribosomal proteins are known to play an important role in translational regulation, and they have been implicated in the control of cellular transformation, tumor growth, aggressiveness and metastasis. Specially, rpL7a activates the trk oncogene by contributing an amino-terminal activating sequence to the receptor kinase domain of trk. Thus, ethanol-induced alteration of rpL7a expression may mediate the promoting effects of ethanol on breast cancer development. PMID- 11759825 TI - Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women. AB - The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted. PMID- 11759827 TI - Apoptotic cell death in mammary adenocarcinoma cells is prevented by soluble factors present in the target organ of metastasis. AB - Target organ of metastasis determines the fate of metastasis. The soluble factors released from one or more cell types in the new stroma may influence growth and survival of metastatic cells. In the present study, we used conditioned media from the kidney, liver and lung, the latter being the target organ of metastasis of murine mammary adenocarcinoma cell lines LM3, LMM3 and F3II, to assess whether the soluble factors released from these organs could modulate in vitro survival of these cell lines after apoptosis-inducing treatments and to investigate the mechanisms involved in this effect. We demonstrate that conditioned medium from lung, but not from liver or kidney, promotes survival of these cells after doxorubicin, cisplatin, agonistic anti-Fas antibody and serum withdrawal treatments. Furthermore, LMM3 cells treated with lung conditioned medium after doxorubicin exposure maintained their tumorigenic capacity and metastatic potential. Neither IGF nor EGF could promote survival but, surprisingly, TGF-beta could reduce sensitivity of LMM3 cells to doxorubicin in vitro. Doxorubicin treatment induced Bax expression and down-regulated Bcl-2 expression. In contrast, lung conditioned medium increased Bcl-2 expression and inhibited doxorubicin-mediated Bcl-2 down-regulation. Neither of those treatments alone modified Bcl-X(L) expression, although co-treatment induced a 3- to 5-fold increase of its expression. These results suggest that the lung microenvironment could promote metastasis of these adenocarcinoma cell lines by increasing survival of metastatic cells, possibly by modulation of Bcl-2 protein family expression. PMID- 11759828 TI - HER-2/neu overexpression and in vitro chemosensitivity to CMF and FEC in primary breast cancer. AB - Available clinical and experimental data on the effect of HER-2/neu overexpression on chemosensitivity are controversial. It was the purpose of this in vitro study to define the association between HER-2/neu overexpression and the sensitivity to the chemotherapeutic drug combinations of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC) of breast cancer cells derived from 140 chemotherapy-naive patients at the time of primary surgery. Both drug combinations were tested at six different concentrations ranging from 6.25-200% peak plasma concentration (PPC). Immunohistochemical detection of HER-2/neu overexpression was performed with the HER-2/neu antibodies, CB11, TAB250 and AO485, in the same tumor specimens. Immunoreactions were determined as negative (0/1+), weakly positive (2+) and strongly positive (3+). However, the antibodies varied in their degrees of sensitivity. Breast cancer samples with strong (3+) HER-2/neu overexpression demonstrated 90% growth inhibition (IC90) at significantly lower PPC values, using the CB11 (p = 0.048), TAB250 (p = 0.007) and AO485 (p < or =0.01) antibodies, and showed 50% growth inhibition (IC50) at significantly lower PPC values, using the CB11 antibody (p = 0.01) compared to their counterparts with lower levels of HER-2/neu expression. When analyzing the group of patients with intermediate and strong HER-2/neu overexpression (2+ and 3+), an association between HER-2/neu overexpression and increased chemosensitivity was seen with the TAB250 (p = 0.044) and AO485 (p = 0.032) antibodies, but not with the CB11 antibody (p =0.8) at the IC90 level. Differences in chemosensitivity between samples with strong HER-2/neu overexpression and those with lower levels were then analyzed separately for CMF and FEC. Both regimens achieved 90% tumor growth inhibition at lower PPC values in samples with strong HER-2/neu overexpression (3+) compared to their counterparts with lower expression levels (AO485 p = 0.011 for CMF, and p = 0.09 for FEC). Cumulative concentration-response plots of tumors responding in vitro with 90% tumor cell inhibition showed a stronger dose dependence for both CMF and FEC among tumor samples with strong HER-2/neu overexpression compared to those with lower levels of expression. In conclusion, the data show that HER-2/neu overexpression was not associated with in vitro drug resistance to CMF or FEC. In contrast, tumors with strong HER-2/neu overexpression demonstrated increased dose-dependent in vitro sensitivity to both the FEC and CMF regimens. PMID- 11759829 TI - Prognostic value of TP53 gene mutation in adjuvant treated breast cancer patients. AB - We investigated the prognostic significance of mutation to the TP53 tumor suppressor gene in a series of 908 breast cancer patients treated with or without adjuvant therapies. The frequency of TP53 mutation detected by single strand conformation polymorphism (SSCP) was 19.4% (176/908) in the overall tumor series. In multivariate analysis, TP53 mutation was independently associated with worse survival in the overall (HR = 2.1, 95% CI [1.5-3.1], P<0.0001), non-adjuvant treated (HR=2.2, 95% CI [1.2-4.2], P=0.017) and adjuvant treated (HR= 2.0, 95% CI [1.3-3.1], P = 0.0009) patients. PMID- 11759830 TI - Desferri-exochelin induces death by apoptosis in human breast cancer cells but does not kill normal breast cells. AB - A major goal of cancer chemotherapy is the identification of cytotoxic compounds that are highly selective for cancer cells. We describe here one such compound - a novel iron chelator, desferri-exochelin 772SM. This desferri-exochelin has unique chemical and pharmacological properties, including extremely high iron binding affinity, the capacity to block iron-mediated redox reactions, and lipid solubility which enables it to enter cells rapidly. At low concentrations, this desferri-exochelin kills T47D-YB and MCF-7 human breast cancer cells by inducing apoptosis, but only reversibly arrests the growth of normal human mammary epithelial cells without cytotoxicity. Since iron-loaded exochelin is ineffective, iron chelation accounts for the efficacy of desferri-exochelin. For both the killing of breast cancer cells and the growth arrest of normal breast epithelial cells, desferri-exochelin was effective at much lower concentrations than the lipid-insoluble iron chelator deferoxamine, which has shown only limited potential as an anti-cancer agent. Growth arrest of progesterone receptor positive T47D-YB cells with the progestin R5020 transiently protects them from the cytotoxic effects of desferri-exochelin, but the cells are killed after cell growth resumes. Similarly, MCF-7 cells arrested with the estrogen antagonist ICI182780 are transiently resistant to killing by desferri-exochelin. Thus the desferri-exochelin is cytotoxic only to actively growing tumor cells. Since desferri-exochelin 772SM can selectively and efficiently destroy proliferating cancer cells without damaging normal cells, it may prove useful for the treatment of cancer. PMID- 11759831 TI - Screening mammography and breast cancer treatment patterns in older women. AB - OBJECTIVE: To examine the impact of mammography screening on treatment options received by a cohort of older breast cancer patients. SETTING AND POPULATION: We studied 718 newly diagnosed breast cancer patients, 67 years and over, diagnosed with TNM Stage I and II disease between 1995 and 1997 at 29 hospitals in five regions. METHODS: Data were collected from patients, surgeons, and medical records. A breast cancer diagnosis was considered to have been by screening mammography if so reported by both patient and medical records. Bivariate and logistic regression were used to identify predictors of a women having her cancer detected by screening mammography and the relationships between mode of detection, stage of disease at diagnosis, and local treatment. RESULTS: Women with high school or greater education were 1.75 times (95%, CI 1.11-2.75) more likely to have their cancers diagnosed by screening mammography than women who had not completed high school, controlling for other factors. Screening found earlier stage disease: 96% of women with mammographically diagnosed cancer had T1 lesions, compared to 81% of women diagnosed by other means (p = 0.001). Women with mammography detected lesions were more likely to have ductal cancer, and to be referred to radiation oncologists more than women diagnosed by other means. Controlling for stage and histology, screening remained associated with a higher likelihood of receiving breast conserving surgery (BCS) with radiation (RT) (OR 1.56, 95%, CI 1.10-2.22) than other local therapies. CONCLUSIONS: Beyond the impact on stage, ductal cancers were more likely to be diagnosed by screening. Mammographically detected lesions were associated with referrals to radiation oncologists and higher rates of BCS and RT. Research is needed to explain the residual independent effects of mammography screening on breast cancer treatment. PMID- 11759832 TI - Meeting medical terminology needs--the Ontology-Enhanced Medical Concept Mapper. AB - This paper describes the development and testing of the Medical Concept Mapper, a tool designed to facilitate access to online medical information sources by providing users with appropriate medical search terms for their personal queries. Our system is valuable for patients whose knowledge of medical vocabularies is inadequate to find the desired information, and for medical experts who search for information outside their field of expertise. The Medical Concept Mapper maps synonyms and semantically related concepts to a user's query. The system is unique because it integrates our natural language processing tool, i.e., the Arizona (AZ) Noun Phraser, with human-created ontologies, the Unified Medical Language System (UMLS) and WordNet, and our computer generated Concept Space, into one system. Our unique contribution results from combining the UMLS Semantic Net with Concept Space in our deep semantic parsing (DSP) algorithm. This algorithm establishes a medical query context based on the UMLS Semantic Net, which allows Concept Space terms to be filtered so as to isolate related terms relevant to the query. We performed two user studies in which Medical Concept Mapper terms were compared against human experts' terms. We conclude that the AZ Noun Phraser is well suited to extract medical phrases from user queries, that WordNet is not well suited to provide strictly medical synonyms, that the UMLS Metathesaurus is well suited to provide medical synonyms, and that Concept Space is well suited to provide related medical terms, especially when these terms are limited by our DSP algorithm. PMID- 11759833 TI - Computer-aided prototype system for nose surgery. AB - Rhinoplasty, or surgery to reshape the nose, is one of the most common of all plastic-surgery procedures. Rhinoplasty can enhance a patient's appearance and self-confidence, may also correct a birth defect or injury, or help relieve some breathing problem. In this paper, we present a three-dimensional (3-D) surgical simulation system, which can assist surgeons in planning rhinoplasty procedures. This system employs computer graphics and image-processing techniques for the simulation of a rhinoplasty. Although the presented algorithms themselves are not new, the proposed system exploits the new idea to apply 3-D morphing for rhinoplasty, and simulation results are useful for the physicians. According to patients' expectation of what they would like their noses to look like, our system simulates expected results. Our tools provide quantitative measurements of a nose structure. Using these quantitative results, surgeons can arrange appropriate preoperative plans for patients. Finally, experimental results and experiences are reported to evaluate the usefulness of the proposed system. PMID- 11759834 TI - Modeling tumor growth and irradiation response in vitro--a combination of high performance computing and web-based technologies including VRML visualization. AB - A simplified three-dimensional Monte Carlo simulation model of in vitro tumor growth and response to fractionated radiotherapeutic schemes is presented in this paper. The paper aims at both the optimization of radiotherapy and the provision of insight into the biological mechanisms involved in tumor development. The basics of the modeling philosophy of Duechting have been adopted and substantially extended. The main processes taken into account by the model are the transitions between the cell cycle phases, the diffusion of oxygen and glucose, and the cell survival probabilities following irradiation. Specific algorithms satisfactorily describing tumor expansion and shrinkage have been applied, whereas a novel approach to the modeling of the tumor response to irradiation has been proposed and implemented. High-performance computing systems in conjunction with Web technologies have coped with the particularly high computer memory and processing demands. A visualization system based on the MATLAB software package and the virtual-reality modeling language has been employed. Its utilization has led to a spectacular representation of both the external surface and the internal structure of the developing tumor. The simulation model has been applied to the special case of small cell lung carcinoma in vitro irradiated according to both the standard and accelerated fractionation schemes. A good qualitative agreement with laboratory experience has been observed in all cases. Accordingly, the hypothesis that advanced simulation models for the in silico testing of tumor irradiation schemes could substantially enhance the radiotherapy optimization process is further strengthened. Currently, our group is investigating extensions of the presented algorithms so that efficient descriptions of the corresponding clinical (in vivo) cases are achieved. PMID- 11759835 TI - ECG data compression using truncated singular value decomposition. AB - The method of truncated singular value decomposition (SVD) is proposed for electrocardiogram (ECG) data compression. The signal decomposition capability of SVD is exploited to extract the significant feature components of the ECG by decomposing the ECG into a set of basic patterns with associated scaling factors. The signal informations are mostly concentrated within a certain number of singular values with related singular vectors due to the strong interbeat correlation among ECG cycles. Therefore, only the relevant parts of the singular triplets need to be retained as the compressed data for retrieving the original signals. The insignificant overhead can be truncated to eliminate the redundancy of ECG data compression. The Massachusetts Institute of Technology-Beth Israel Hospital arrhythmia database was applied to evaluate the compression performance and recoverability in the retrieved ECG signals. The approximate achievement was presented with an average data rate of 143.2 b/s with a relatively low reconstructed error. These results showed that truncated SVD method can provide an efficient coding with high-compression ratios. The computational efficiency of the SVD method in comparing with other techniques demonstrated the method as an effective technique for ECG data storage or signals transmission. Index Terms Data compression, electrocardiogram, feature extraction, quasi-periodic signal, singular value decomposition. PMID- 11759836 TI - Wavelet-based space-frequency compression of ultrasound images. AB - This paper describes the compression of grayscale medical ultrasound images using a recent compression technique, i.e., space-frequency segmentation (SFS). This method finds the rate-distortion optimal representation of an image from a large set of possible space-frequency partitions and quantizer combinations and is especially effective when the images to code are statistically inhomogeneous, which is the case for medical ultrasound images. We implemented a compression application based on this method and tested the algorithm on representative ultrasound images. The result is an effective technique that performs better than a leading wavelet-transform coding algorithm, i.e., set partitioning in hierarchical trees (SPIHT), using standard objective distortion measures. To determine the subjective qualitative performance, an expert viewer study was run by presenting ultrasound radiologists with images compressed using both SFS and SPIHT. The results confirmed the objective performance rankings. Finally, the performance sensitivity of the space-frequency codec is shown with respect to several parameters, and the characteristic space-frequency partitions found for ultrasound images are discussed. PMID- 11759837 TI - A computer-based method for the assessment of body-image distortions in anorexia nervosa patients. AB - A computer-based method for the assessment of body-image distortions in anorexia nervosa and other eating-disorder patients is presented in this paper. At the core of the method is a realistic pictorial simulation of lifelike weight changes, applied to a real source image of the patient. The patients, using a graphical user interface, adjust their body shapes until they meet their self perceived appearance. Measuring the extent of virtual fattening or slimming of a body with respect to its real shape and size allows direct quantitative evaluation of the cognitive distortion in body image. In a preliminary experiment involving 33 anorexia-nervosa patients, 70% of the subjects chose an image with simulated visual weight gain between 8%-16% as their "real" body image, while only one of them recognized the original body image. In a second experiment involving 30 healthy participants, the quality of the weight modified images was evaluated by pairwise selection trials. Over a weight change range from -16% to +28%, in about 30% of the trials, artificially modified images were mistakenly taken as "original" images, thus demonstrating the quality of the artificial images. The method presented is currently in a clinical validation phase, toward application in the research, diagnosis, evaluation, and treatment of eating disorders. PMID- 11759838 TI - Compact storage of medical images with patient information. AB - Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images to reduce storage and transmission overheads. The text data are encrypted before interleaving with images to ensure greater security. The graphical signals are compressed and subsequently interleaved with the image. Differential pulse-code-modulation and adaptive-delta-modulation techniques are employed for data compression, and encryption and results are tabulated for a specific example. PMID- 11759839 TI - OsIAA1, an Aux/IAA cDNA from rice, and changes in its expression as influenced by auxin and light. AB - The Aux/IAA class of genes are rapidly induced by exogenous auxins and have been characterized extensively from many dicot species like Arabidopsis, Glycine max and Pisum sativum. We report here the isolation and characterization of rice (Oryza sativa L. subsp. Indica) OsIAA1 cDNA as a monocot member of the Aux/IAA gene family. The predicted amino acid sequence of OsIAA1 corresponds to a protein of ca. 26 kDa, which harbors all four characteristic domains known to be conserved in Aux/IAA proteins. The conservation of these Aux/IAA genes indicates that auxins have essentially a similar mode of action in monocots and dicots. Northern blot analysis revealed that the OsIAA1 transcript levels decrease in the excised coleoptile segments on auxin starvation, and the level is restored when auxin is supplemented; the increase in OsIAA1 transcript level was apparent within 15 to 30 min of auxin application. Auxin-induced OsIAA1 expression appears to be correlated with the elongation of excised coleoptile segments. In light grown rice seedlings, OsIAA1 is preferentially expressed in roots and basal segment of the seedling, whereas in the etiolated rice seedlings, the OsIAA1 transcripts are most abundant in the coleoptile. A comparative analysis in light- and dark-grown seedling tissues indicates that the OsIAA1 transcript levels decrease on illumination. PMID- 11759840 TI - Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120. AB - The nucleotide sequence of the entire genome of a filamentous cyanobacterium, Anabaena sp. strain PCC 7120, was determined. The genome of Anabaena consisted of a single chromosome (6,413,771 bp) and six plasmids, designated pCC7120alpha (408,101 bp), pCC7120beta (186,614 bp), pCC7120gamma (101,965 bp), pCC7120delta (55,414 bp), pCC7120epsilon (40,340 bp), and pCC7120zeta (5,584 bp). The chromosome bears 5368 potential protein-encoding genes, four sets of rRNA genes, 48 tRNA genes representing 42 tRNA species, and 4 genes for small structural RNAs. The predicted products of 45% of the potential protein-encoding genes showed sequence similarity to known and predicted proteins of known function, and 27% to translated products of hypothetical genes. The remaining 28% lacked significant similarity to genes for known and predicted proteins in the public DNA databases. More than 60 genes involved in various processes of heterocyst formation and nitrogen fixation were assigned to the chromosome based on their similarity to the reported genes. One hundred and ninety-five genes coding for components of two-component signal transduction systems, nearly 2.5 times as many as those in Synechocystis sp. PCC 6803, were identified on the chromosome. Only 37% of the Anabaena genes showed significant sequence similarity to those of Synechocystis, indicating a high degree of divergence of the gene information between the two cyanobacterial strains. PMID- 11759841 TI - Characterization of expressed genes in the SLL2 region of self-compatible Arabidopsis thaliana. AB - Self-incompatibility in Brassica species is regulated by a set of S-locus genes: SLG, SRK, and SP11/SCR. In the vicinity of the S-locus genes, several expressed genes, SLL2 and SP2/ClpP, etc., were identified in B. campestris. Arabidopsis thaliana is a self-compatible Brassica relative, and its complete genome has been sequenced. From comparison of the genomic sequences between B. campestris and A. thaliana, microsynteny between gene clusters of Arabidopsis and Brassica SLL2 regions was observed, though the S-locus genes, SLG, SRK, and SP11/SCR were not found in the region of Arabidopsis. Almost all genes predicted in this region of Arabidopsis were expressed in both vegetative and reproductive organs, suggesting that the genes in the SLL2 region might not be related to self-incompatibility. Considering the recent speculation that the S-locus genes were translocated as a single unit between Arabidopsis and Brassica, the translocation might have occurred in the region between the SLL2 and SP7 genes. PMID- 11759844 TI - Cardiovascular diseases: causes, surveillance and prevention. PMID- 11759842 TI - Generation of RCAS vectors useful for functional genomic analyses. AB - Avian leukosis type A virus-derived retroviral vectors have been used to introduce genes into cells expressing the corresponding avian receptor tv-a. This includes the use of Replication-Competent Avian sarcoma-leukosis virus (ASLV) long terminal repeat (LTR) with Splice acceptor (RCAS) vectors in the analysis of avian development, human and murine cell cultures, murine cell lineage studies and cancer biology. Previously, cloning of genes into this virus was difficult due to the large size of the vector and sparse cloning sites. To overcome some of the disadvantages of traditional cloning using the RCASBP-Y vector, we have modified the RCASBP-Y to incorporate "Gateway" site-specific recombination cloning of genes into the construct, either with or without HA epitope tags. We have found the repetitive "att" sequences, which are the targets for site specific recombination, do not impair the production of infectious viral particles or the expression of the gene of interest. This is the first instance of site-specific recombination being used to generate retroviral gene constructs. These viral constructs will allow for the efficient transfer and expression of cDNAs needed for functional genomic analyses. PMID- 11759845 TI - Surveillance of stroke: a global perspective. AB - For preventive strategies to be efficient, it is essential to have information on the pattern of disease and exposure to major risk factors that predict future diseases in the population. Basic epidemiological data such as mortality rates are reported for less than one-third of the world's population and are almost exclusively from developed countries. However, it is the developing countries, particularly those in rapid economic and demographic transition, which will experience a major rise in ageing-related diseases. The World Health Organization is intensifying the development and implementation of simple, sustainable surveillance systems that can be used in many different settings around the world. Unlike heart disease and cancer, stroke is a clinically defined disease, which makes it possible to identify trends in different countries irrespective of access to technological equipment. A stepwise approach to increasing detail in the data to be collected for surveillance of stroke is suggested. This will allow countries with different levels of resources and capacity in their health systems to collect useful information for policy. PMID- 11759846 TI - Coronary heart disease trends in four United States communities. The Atherosclerosis Risk in Communities (ARIC) study 1987-1996. AB - OBJECTIVE: The objective of this paper is to report trends in mortality due to coronary heart disease (CHD), rates of first and recurrent hospitalized myocardial infarction, and survival after myocardial infarction in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 1996. METHOD: The ARIC study used retrospective community surveillance to monitor admissions to acute care hospitals and deaths due to CHD (both in- and out-of-hospital) among all residents 35-74 years of age. The surveillance areas included over 360 000 men and women in four communities: Forsyth County, North Carolina; the city of Jackson, Mississippi; eight northern suburbs of Minneapolis, Minnesota; and Washington County, Maryland. RESULTS: The annual age-adjusted mortality rate of CHD fell 3.2% (95% CI: 2.0, 4.3) among men and 3.8% (95% CI: 1.9, 5.6) among women. The greater part of the decline took place between 1987 and 1991. Significant declines were observed for both in-hospital and out-of-hospital CHD death. Significant improvements in case-fatality were also observed. Recurrent hospitalized myocardial infarction event rate fell an average of 1.9% per year among men (95% CI: 0.7, 3.1) and 2.1% (95% CI: 0.3, 3.9) among women. Average annual per cent change in incident hospitalized myocardial infarction was not statistically significant, except in blacks where there was evidence of an increase over time. CONCLUSION: Factors associated with the occurrence of recurrent hospitalized myocardial infarction, as well as those creating a better chance of survival after an event (including reductions in sudden death), were likely the prominent components in the recent decline in CHD mortality in ARIC communities. PMID- 11759847 TI - Surveillance of ischaemic heart disease: results from the Italian MONICA populations. AB - BACKGROUND: The major objectives are to report on coronary event mortality, incidence and attack rates and changes over time observed in the Italian MONICA populations and to assess if trends are consistent when different disease definitions are considered. An analysis of diagnostic agreement between clinical and MONICA categories is presented in the context of developing a model for estimating disease incidence in a population, based on currently available data. METHODS: Data were provided by the three Italian MONICA (MONItoring trends and determinants of CArdiovascular diseases) registers. The areas of Brianza and Friuli, both located in northern Italy, completed the 10-year period of registration. Data from the MONICA Latina area, located close to Rome, were limited to the first 3 years of registration. These data are used for assessing geographical differences in rates in the mid- 1980s and estimating the diagnostic agreement between International Classification of Diseases (ICD) codes and MONICA categories. Two diagnostic aggregates have been used: the standard MONICA diagnostic definition for myocardial infarction (MI), which includes non-fatal definite myocardial infarction and fatal coronary events, and the coronary event definition which includes, in addition, non-fatal possible myocardial infarctions. RESULTS: From the mid-1980s to the mid-1990s, a considerable reduction in all-cause, cardiovascular and coronary mortality rates occurred in the monitored populations. Data from the MONICA registers confirm the accuracy of official reports of death rates and changes in Italy. Comparisons of time differences in attack and incidence rates of myocardial infarction and all coronary events indicate that the impact of the more severe manifestations of coronary heart diseases (fatal coronary event and acute MI) reduced during the period of observation, but when less severe events (minor myocardial infarction and angina pectoris) are considered, the overall impact of the disease on the population remained stable. CONCLUSION: Epidemiological surveillance of coronary syndromes is relevant over this time period of impressive changes in prevention and treatment. Continuing restrictions in available resources necessitate the development of simplified registration systems. PMID- 11759848 TI - A national record linkage to study acute myocardial infarction incidence and case fatality in Sweden. AB - BACKGROUND: During the last decades substantial temporal changes, as well as population differences, in coronary heart disease mortality have occurred in Sweden. There is little information to what extent these changes and differences also apply to myocardial infarction incidence. The aim of this paper was to describe the methods used to identify cases in a recently developed National Acute Myocardial Infarction Register in Sweden, and to present estimates of incidence and case fatality in Sweden. MATERIAL AND METHODS: Incident cases of acute myocardial infarction (AMI) were identified by record linkage of routinely collected data on hospital discharges and deaths. Case fatality within 28 days was ascertained by linkage of incident cases to the National Cause of Death Register. RESULTS: About 40 000 new cases of AMI per year were recorded in Sweden during 1987-1995. Well-known differences in incidence with regard to age and gender were observed, as well as a decline in incidence between 1987 and 1995. A similar case fatality was seen in men and women aged 30-89 among hospitalized cases. When fatal cases outside hospital were also considered the case fatality was somewhat higher in men. Examination of medical records for a national sample of ischaemic heart disease patients suggested a high sensitivity (94%) and a high positive predictive value (86%) for ICD-9 code 410 in hospital discharge data with regard to definite AMI. CONCLUSIONS: The National Acute Myocardial Infarction Register offers a new possibility to study the incidence of AMI, as well as case fatality, in Sweden. PMID- 11759849 TI - Trends in coronary risk factors in the WHO MONICA project. AB - BACKGROUND: The World Health Organization (WHO) MONICA Project was established to determine how trends in event rates for coronary heart disease (CHD) and, optionally, stroke were related to trends in classic coronary risk factors. Risk factors were therefore monitored over ten years across 38 populations from 21 countries in four continents (overall period covered: 1979-1996). METHODS: A standard protocol was applied across participating centres, in at least two, and usually three, independent surveys conducted on random samples of the study populations, well separated within the 10-year study period. RESULTS: Smoking rates decreased in most male populations (35-64 years) but in females the majority showed increases. Systolic blood pressure showed decreasing trends in the majority of centres in both sexes. Mean levels of cholesterol generally showed downward trends, which, although the changes were small, had large effects on risk. There was a trend of increasing body mass index (BMI) with half the female populations and two-thirds of the male populations showing a significant increase. CONCLUSIONS: It is feasible to monitor the classic CHD risk factors in diverse populations through repeated surveys over a decade. In general, the risk factor trends are downwards in most populations but in particular, an increase in smoking in women in many populations and increasing BMI, especially in men, are worrying findings with significant public health implications. PMID- 11759850 TI - Coronary risk factors: new perspectives. AB - The predisposing and precipitating causes of acute myocardial infarction (MI) are multiple; furthermore, different individuals may have different susceptibility, to a large extent genetically determined, to each of them. In spite of the complex aetiology of MI and of our limited knowledge of the causes responsible for the formation of persistent occlusive thrombosis in epicardial coronary arteries, the achievements obtained by controlling traditional risk factors are remarkable. Traditional risk factors, however, have a limited sensitivity among subjects with low/moderate levels of risk. Furthermore, in particular among subjects at medium risk, current preventive strategies are limited by the low incidence of preventable events which makes it necessary to also treat the vast majority of subjects who would not develop cardiac events even without any treatment. An improvement in preventive strategies for IHD can be achieved with the identification of: (1) new risk factors; (2) genotypes enhancing the susceptibility to specific risk factors; (3) phenotypes and genotypes making patients susceptible to specific preventive strategies; (4) genotypes protecting from risk factors. Although a word of caution is necessary as a number of recent studies on genetic markers, on new risk factors and on the interaction between genetic markers and environment have failed to withstand the rigour of population based studies, the early findings available to date suggest that cost-effective preventive strategies based on individual susceptibility to specific predisposing and precipitating causes of MI may become a reality in the foreseeable future. PMID- 11759851 TI - Social inequality, ethnicity and cardiovascular disease. AB - BACKGROUND: Epidemiological research on cardiovascular risk factors has led to important advances in prevention science by providing insights that have now resulted in substantial reductions in mortality. This research used the variation in risk among individuals as the guide to causal exposures. Large differentials remain among socio-demographic groups, however, and the causes of these differentials may be distinctly different from those observed at the individual level. METHODS: Vital statistics and census data from the US and selected regions were used in an ecologic analysis. RESULTS: In 1996 heart disease mortality in the US varied from 156/100 000 among African-American women to 51/100 000 among Asian women; similar differentials were observed for men. Income equality was correlated with heart disease mortality among the 47 largest US cities (r = -0.4; P = 0.006). Independent of income equality, racial segregation was also associated with risk of death from cardiovascular disease in this sample of cities. CONCLUSIONS: Social processes generate marked differentials in heart disease mortality among demographic groups. In the US, death rates are currently 2-3 times higher among African Americans compared to Asians. Broadly speaking, this variation results from their separate cultural legacies, based on well recognized lifestyle factors and dietary patterns. Ecological comparisons across cities that share similar lifestyle patterns suggest that income inequality and patterns of racial discrimination are each associated with large variation in mortality in a similar manner. Racism and social inequality can be conceptualized as social causes of excess cardiovascular mortality that may not be measurable at the individual level. PMID- 11759852 TI - Estimating population-based incidence and prevalence of major coronary events. AB - BACKGROUND: Population-based data on coronary events are generally lacking for large areas, such as at the nation-wide level. While mortality data are currently and exhaustively collected in all developed countries and in a few developing countries, incidence and prevalence are often available only for certain subgroups of the population under study. METHODS: We propose to estimate population-based incidence and prevalence of coronary events through a mathematical method using mortality and survival data as input, and to forecast coronary event occurrence using an age, period and cohort approach. The method reconstructs incidence and prevalence of major coronary events in Italy from 1970 to 1997 and projects trends up to the year 2007 using survival data on coronary events from the Area Friuli-MONICA (MONItoring of CArdiovascular diseases) register. RESULTS: Major coronary event incidence has been decreasing since 1977 for men and since 1974, for women. Conversely, major coronary event prevalence increased up to the end of the 1980s for men and up to the early 1980s for women, and it has been declining thereafter. Major coronary event prevalence results from three main effects: increasing survival, population ageing, and incidence trend. CONCLUSIONS: Availability of national population data, collection of population-based survival data from the MONICA registers and appropriate statistical and mathematical methods help to estimate and project incidence and prevalence trends for major coronary events. This information is essential to plan and implement actions aimed at improving medical care services, and to evaluate the impact of public health interventions as well as spontaneously changing habits. Incidence, prevalence, mortality, projections, ischaemic heart disease, coronary events PMID- 11759853 TI - Socio-occupational differences in acute myocardial infarction case-fatality and coronary care in a northern Italian population. AB - AIMS: To appraise 28-day case-fatality of myocardial infarction (MI) among socio occupational classes; to assess the consistency of the results for different degrees of MI severity; to explore if such differences are related to differences in management and treatment of the acute attack. METHODS: All coronary events (n = 1077), registered in 1993-1994 among the 35-64 year old male residents in MONICA Area Brianza were investigated and classified into diagnostic categories according to MONICA criteria. For all cases standardized information on acute coronary care and interventions before and during hospitalization was collected. Classification of social classes was derived from the Erikson-Goldthorpe Portocarero social class scheme, based on information on occupational characteristics widely available in European countries. RESULTS: An increasing rate of case-fatality for decreasing levels of socio-occupational class was found. The social gradient resulted mainly from the higher incidence of out-of hospital cardiac arrests. Treatment before and during the acute attack cannot explain the observed differences. CONCLUSION: Combining these results with those obtained in other MONICA centres, it appears that further decreases in coronary mortality might be achieved through specific programmes addressed in particular to the reduction of out-of-hospital case-fatality in lower social classes. PMID- 11759854 TI - Differences in cardiovascular disease mortality and major risk factors between districts in Oslo. An ecological analysis. AB - BACKGROUND: The level of mortality from cardiovascular disease (CVD), coronary heart disease (CHD) and from all causes varies considerably within Oslo. The purpose of this study was to examine these differences according to cardiovascular risk factors and socioeconomic variables at the district level. METHODS: Total mortality rates and cardiovascular mortality rates for subjects aged 45-74 years in 1991-1995, and their relationship to cardiovascular risk factors and socioeconomic indicators in the 25 districts of Oslo were studied. Cardiovascular risk factors were based on data from 40 year olds in 1985-1988. The following variables were used as independent variables in the regression analyses to explain differences between the districts: daily smoking, cholesterol level, systolic blood pressure, education and income. RESULTS: Mortality rates were strongly related to cardiovascular risk factors and to socio-economic indicators, with correlation coefficients (Pearson) of 0.74 for smoking and CVD mortality, and -0.78 for high income and CHD mortality. Smoking explained 70% of the differences in mortality from all causes for men and 46% for women, and 61% and 49% of the differences in CVD mortality for men and women respectively. Diastolic blood pressure and total cholesterol were closely related to socioeconomic indicators and to smoking, but the relative strength of the cardiovascular risk factors in the multivariate analyses differed for males and females. CONCLUSION: diovascular risk factors and socioeconomic indicators at the population level were strongly related to mortality, and explained a large proportion of the differences in mortality between different districts of Oslo in the 1990s. PMID- 11759855 TI - Prevention of cardiovascular disease and the future of cardiovascular disease epidemiology. AB - BACKGROUND: Coronary heart disease is preventable. The improved interpretation of risk factors, in vivo non-invasive measuring of arteries, brain and heart, and proven efficacy of both non-pharmacological and pharmaceutical therapies provides the model for both cardiovascular prevention programmes and new epidemiological studies. METHODS: Risk factors can be subdivided into those related to the development of atherosclerosis with relatively long incubation periods, and risk factors that moderate the changes in atherosclerotic plaque, thrombosis and fibrinolysis, i.e. those with short incubation periods, or proximate risk factors. RESULTS: The level of ApoB containing lipoproteins, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are the primary determinants of atherosclerosis. Using non-invasive methods of measuring atherosclerosis, we can evaluate the efficacy of intervention to both prevent the development of atherosclerosis and the progression of disease. The importance of proximate risk factors, especially inflammatory markers, is less estimated than long incubation period factors. It is possible that a combination of measures of subclinical atherosclerosis and proximate risk factors may provide the best estimate of the risk of clinical disease, especially among higher risk older individuals. CONCLUSIONS: The measurement of subclinical disease and new proximate risk factors (i.e. inflammation, fibrinolysis) may be useful for comparing reported differences in rates of clinical disease among populations and monitoring the emerging epidemic of cardiovascular disease in countries that currently have low death rates due to cardiovascular disease. PMID- 11759856 TI - Associations between serum antibody levels to periodontal pathogens and early onset periodontitis. AB - BACKGROUND: The role of antibodies to periodontal microorganisms in the development of periodontal tissue destruction is still unclear. The aim of this study was to investigate the association between serum levels of IgG, IgA, and IgM antibodies to 6 periodontal microorganisms and clinical subtypes of varying severity of early-onset periodontitis (EOP) in young African American adults. METHODS: The study group consisted of 159 African Americans aged 19 to 25 years (mean 22 years) and included 97 cases with EOP and 62 controls with no clinical signs of EOP. These subjects were selected from a nationally representative sample of adolescents who received an oral examination as part of the National Survey of Oral Health of United States Children in 1986-1987. The group was examined clinically a second time 6 years later and blood samples were collected. Serum levels of IgG, IgA, and IgM reactive to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, and Fusobacterium nucleatum were assessed. RESULTS: Serum levels of IgG and IgA antibody reactive to P. gingivalis and A. actinomycetemcomitans and IgA antibody to P. intermedia were significantly higher in generalized EOP cases compared to healthy controls. IgM antibody levels did not show any significant associations with EOP for any of the 6 bacterial species tested. There were no significant differences in antibody levels between controls and the 13 subjects in our study who were classified with localized EOP. CONCLUSIONS: The findings suggest that antibodies to P. gingivalis, P. intermedia, and A. actinomycetemcomitans may play a significant role in the pathogenesis of EOP. Substantial longitudinal studies that monitor antibody levels and avidity prior to disease onset, during progression, and following clinical intervention will be necessary to fully understand the role of this component of the immune response in protection versus tissue destruction and the potential use in EOP risk assessment and disease management. PMID- 11759857 TI - Comparison of 2 techniques of subepithelial connective tissue graft in the treatment of gingival recessions. AB - BACKGROUND: The clinical outcome of connective tissue grafts in the treatment of gingival recessions has been documented in numerous studies. However, no attempt has been made to correlate the postoperative mucogingival changes with the surgical parameters. The present retrospective clinical study was undertaken to 1) evaluate root coverage and mucogingival changes 1 to 1.5 years following treatment of Miller's Class I and II recession defects using 2 variants of the subepithelial connective tissue graft (SCTG) procedure, and 2) assess the effect of the surgical parameters on the postoperative gingival width. METHODS: Thirty one recessions in 10 patients treated with the envelope technique (E) and 31 recessions in 11 patients treated with coronally positioned flap combined with connective tissue graft (CP) were retrospectively analyzed to evaluate: 1) percentage of root coverage obtained with the 2 procedures and variations in width of keratinized tissue (KT) 1 to 1.5 years postsurgery, and 2) the effect of the surgical parameters on the postoperative gingival width. RESULTS: Results showed a mean root coverage percentage of 89.6 +/- 15% for the E group and 94.7 +/- 11.4% for the CP group; the difference between groups was statistically insignificant (P = 0.1388). Mean KT increased significantly from 1.4 +/- 1.1 mm presurgery to 4.5 +/- 1.1 mm postsurgery for the E group while a minor increase in KT was observed in the CP group (2 +/- 1.5 mm presurgery versus 2.7 +/- 1.6 mm postsurgery). For both treatment groups, the mean postsurgical width of keratinized tissue (POSTKT) was found to be mathematically correlated with the mean presurgical width of keratinized tissue (PREKT) and the corono-apical height of the graft that remained exposed (GE) coronal to the flap margin in the recipient site. CONCLUSIONS: Treatment of human gingival recession defects by the 2 variants of SCTG resulted in significant recession reduction. When SCTG is grafted beneath alveolar mucosa using the combined technique (CP), transformation of the mucosa into keratinized tissue does not seem to occur, at least within 1 to 1.5 years postsurgery. The treatment outcome in terms of keratinized tissue width seems to be correlated with the presurgical gingival dimensions and the height of the graft that remains exposed at the end of the surgical procedure. PMID- 11759858 TI - Comparative 6-month clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recession. AB - BACKGROUND: Different techniques have been proposed for the treatment of gingival recessions. This study compared the clinical results of gingival recession treatment using a subepithelial connective tissue graft and an acellular dermal matrix allograft. METHODS: Nine patients with bilateral Miller Class I or II gingival recessions were selected. A total of 30 recessions were treated and randomly assigned to the test group and the contralateral recession to the control group. In the control group, the exposed root surfaces were treated by the placement of a connective tissue graft in combination with a coronally positioned flap; in the test group, an acellular dermal matrix allograft was used as a substitute for palatal donor tissue. Probing depth, clinical attachment level, gingival recession, and width of keratinized tissue were measured 2 weeks prior to surgery and 3 and 6 months postsurgery. RESULTS: There were no statistically significant differences between the test group and the control group in terms of recession reduction, clinical attachment gain, and reduction in probing depth. The control group had a statistically significant increased area of keratinized tissue after 3 months compared to the test group. Both procedures, however, produced an increase in keratinized tissue after 6 months, with no statistically significant difference. CONCLUSION: The acellular dermal matrix allograft may be a substitute for palatal donor tissue in root coverage procedures. PMID- 11759859 TI - Periodontal disease in pregnancy complicated by type 1 diabetes mellitus. AB - BACKGROUND: Systemic disease and hormonal changes have been implicated as complicating factors for periodontal disease. Diabetes has been identified as a risk factor for periodontal disease, and diabetics can experience periodontal destruction at an earlier age than non-diabetic individuals. Increased hormone levels during pregnancy can contribute to increased gingival inflammation. The purpose of this study was to examine the association of type 1 diabetes mellitus (DM) on the periodontal status of pregnant women. METHODS: Thirty-three (13 diabetic and 20 non-diabetic) subjects, 20 to 39 weeks gestation, participated in this study. The mean age of the diabetics and non-diabetics was 28.5 +/- 7.1 (SD) and 27.0 +/- 7.3 years, respectively. The following parameters were assessed at Ramfjord's reference teeth: plaque index (PI), gingival inflammation (GI), probing depth (PD), gingival margin (GM) location, and clinical attachment level (CAL). RESULTS: Diabetic subjects had significantly (P<0.001) higher PI (1.48 +/- 0.69) and GI (1.77 +/- 0.44) scores than non-diabetics (PI = 0.63 +/- 0.38; GI = 0.93 +/- 0.48). Mean PD for diabetics (2.95 +/- 0.69 mm) was significantly different (P<0.024) from that of non-diabetics (2.44 +/- 0.32 mm). Although mean GM location was coronal to the cemento-enamel junction (CEJ) in both groups, gingival margins were at a more apical position (P<0.001) in the diabetics (-0.20 +/- 1.24 mm) compared to non-diabetics (-1.76 +/- 0.53 mm). Mean CAL values also varied significantly (P<0.001) between diabetics (2.60 +/- 1.54 mm) and non diabetics (0.68 +/- 0.65 mm). Significant differences were seen for GI (P<0.001), PD (P=0.005), GM location (P<0.001), and CAL (P<0.001) when assessing the effect of diabetes and controlling for plaque. When assessing the effect of plaque and controlling for diabetes, the only significant difference was GI (P=0.001). CONCLUSIONS: The results of this study demonstrate that periodontal inflammation and destruction are increased in pregnant diabetics as compared to non-diabetic pregnant patients. These findings may have implications for diabetic control and, hence, maternal and fetal outcomes in pregnant diabetic patients. PMID- 11759860 TI - The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight. AB - BACKGROUND: In Alabama, low birth weight (LBW) infants are about 20 times more likely to die before their first birthday compared to normal birth weight infants. While the rate of LBW has been consistently higher among African Americans compared to whites, there has been a gradual increase in LBW for both African Americans and whites over the last 15 years. In an attempt to identify modifiable risk factors for LBW, we have previously reported that a pregnant woman's poor periodontal health may be an independent risk factor for low birth weight. METHODS: A predominantly African American and socioeconomically homogeneous group of 448 women was followed from the second trimester of their first pregnancy. Thirty-nine LBW cases were observed at the end of follow-up. Using 17 preterm LBW cases and 63 randomly selected controls from the above cohort, the periodontal pathogen-specific maternal serum IgG levels during the second trimester of pregnancy were evaluated in relation to birth weight of the infant, while controlling for known risk factors for LBW. RESULTS: Porphyromonas gingivalis (P.g.)-specific maternal serum IgG levels were higher in the LBW group (mean 58.05, SE = 20.00 microg/ml) compared to the normal birth weight (NBW) group (mean 13.45, SE = 3.92 microg/ml; P= 0.004). Women with higher levels of P.g.-specific IgG had higher odds of giving birth to LBW infants (odds ratio [OR] = 4.1; 95% confidence interval [CI] for odds ratio = 1.3 to 12.8). This association remained significant after controlling for smoking, age, IgG levels against other selected periodontal pathogens, and race. CONCLUSIONS: Low birth weight deliveries were associated with a higher maternal serum antibody level against P. gingivalis at mid-trimester. PMID- 11759861 TI - Surgical therapy of peri-implant disease: a 3-year follow-up study of cases treated with 3 different techniques of bone regeneration. AB - BACKGROUND: Advanced peri-implant intrabony defects require comprehensive surgical treatment regimens different from periodontal therapy strategies. The purpose of this longitudinal trial was to evaluate the peri-implant outcomes following guided bone regeneration with 3 treatment protocols. METHODS: In 25 patients, 41 peri-implant defects with supporting bone loss >50% of the implant length were treated with flap surgery plus autogenous bone grafts alone (FG) (controls, n = 12) plus non-resorbable (FGM) (test 1, n = 20) or bioabsorbable barriers (FGRM) (test 2, n = 9) and supportive antimicrobial therapy. Following submerged healing, the membranes were removed (FGM), and the peri-implant probing depths (PD), probing bone levels (BL), mobility scores (PT), and intrabony defect height (DH) were radiographically evaluated at baseline, 6 months, and 1 and 3 years post-therapy. RESULTS: Non-surgical/anti-infective therapy resulted in a limited improvement of PD scores after 6 months. At the 3-year visit, surgical treatment revealed significant changes from baseline for the controls and both of the test groups for PD: 5.1 +/- 2.7 mm (FG), 5.4 +/- 3.0 mm (FGM), and 2.6 +/- 1.6 mm (FGRM), and for BL: 3.2 +/- 2.4 mm (FG), 3.4 +/- 2.4 mm (FGM), and 2.3 +/- 1.6 mm (FGRM), Mann-Whitney test, P < or = 0.05. The changes for DH and PT were significant only for FG- and FGM-treated subjects. The overall improvement for FGRM-treated patients during the 3-year observation was less marked. However, the differences between the 3 surgical treatment protocols did not affect the treatment outcomes after 3 years. CONCLUSIONS: Autogenous bone grafting is an appropriate treatment regimen to augment open crater-formed peri-implant defects. Although certain clinical situations require an additional fixation of barrier membranes, their routine application should be approached with caution. PMID- 11759862 TI - Longitudinal comparison of the periodontal status of patients with moderate to severe periodontal disease receiving no treatment, non-surgical treatment, and surgical treatment utilizing individual sites for analysis. AB - BACKGROUND: The progression of periodontal disease without treatment and the response of existing periodontal disease to various types of treatment have been studied extensively. Many past studies have used the mean of the patient's probing depths or attachment levels to evaluate disease progression as opposed to following changes in individual sites or teeth. The purpose of the current study was to evaluate the response of individual teeth to treatment or non-treatment. METHODS: The records from a private periodontal practice were reviewed to find patients with complete periodontal examinations that were recorded at least 1 year apart. Patients who fit these criteria were divided into those who had none of the recommended treatment (untreated, n = 30); those who had only non-surgical treatment (partially treated, n = 20); and a control group who had completed all recommended treatment (surgically treated, n = 41). The data for each tooth of each patient were placed in a database and analyzed using the method of generalized estimating equations (GEE) to test for associations between increase or decrease in probing depths and various initial clinical parameters while adjusting for significant confounders. RESULTS: Teeth that received no treatment or non-surgical treatment showed significant increases in probing depths, worsening of prognosis, worsening of furcation involvement, and increases in mobility when compared to surgically treated teeth. Teeth that received surgical treatment showed significant decreases in probing depths. No significant difference was noted between teeth that had no treatment and teeth that had non surgical treatment. CONCLUSIONS: When individual teeth are used as the basis for analysis, teeth that receive no treatment or non-surgical treatment show a significant worsening of probing depths, furcations, mobility, and prognosis when compared to teeth that receive surgical treatment, while surgically treated teeth show significant improvement in probing depths. PMID- 11759863 TI - Attachment of human periodontal ligament cells to enamel matrix-derived protein is mediated via interaction between BSP-like molecules and integrin alpha(v)beta3. AB - BACKGROUND: Although enamel matrix-derived protein (EMD) can stimulate attachment of human periodontal ligament (HPDL) cells to the root surface, the biological mechanism of this phenomenon is unclear. The purpose of this study was to determine which molecules in EMD are involved in the attachment of HPDL cells, and which types of integrins on the cell surface mediate the interaction between the cells and EMD. METHODS: HPDL explants were obtained from tooth surfaces extracted from 4 individuals, and cells taken from the individual explants were separately harvested and subcultured through as many as 5 passages. Cells were incubated on EMD-coated culture plates with and without neutral antibodies for integrins or RGD-sequence blocking peptides and stained with toluidine blue. Proteins in EMD that were able to induce cell attachment were identified by incubating sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) replicas with HPDL cells; the cell-binding regions were detected by staining the cells with toluidine blue. Characteristics of the cell-binding proteins in the EMD were identified by Western blot analysis. RESULTS: It was shown that anti alpha(v)beta3 antibody and GRGDSP peptide markedly reduced attachment of HPDL cells to EMD. When the cells were incubated with SDS-PAGE replicas, distinct cell attachment was observed at a molecular mass of approximately 55 kDa. The cell binding ability of this protein was completely blocked by treatment with anti alpha(v)beta3 antibody or GRGDSP peptide. In the Western blot analysis, the 55 kDa protein was recognized by anti-bone sialoprotein (BSP) antibody as a single band. CONCLUSIONS: Our study provides the first evidence that the attachment of HPDL cells to EMD can be mediated by interaction between a BSP-like molecule and integrin alpha(v)beta3 on the cell surface. PMID- 11759864 TI - The effects of interleukin-10 depletion in vivo on the immune response to Porphyromonas gingivalis in a murine model. AB - BACKGROUND: The immune response to Porphyromonas gingivalis in the mouse abscess model is known to be dependent upon CD4 T-cell activation and the regulatory role of cytokines. The role of interleukin-10 (IL-10) in this mouse model was examined in vivo. METHODS: One-week-old, female BALB/c mice were divided into 4 groups. Groups 1 and 2 were given intraperitoneal (i.p.) injections of phosphate buffered saline (PBS) weekly for 5 weeks. Group 3 was given an i.p. injection of rat immunoglobulin. Group 4 was injected with rat anti-IL-10 antibodies. At week 6, group 1 was sham-immunized with PBS, and groups 2, 3, and 4 were injected with P. gingivalis lipopolysaccharide (Pg-LPS) weekly for 2 weeks. One week after the final immunization, delayed-type hypersensitivity (DTH) was assessed by footpad swelling to Pg-LPS. The level of serum antibodies to Pg-LPS and IFN-gamma (IFN gamma) was determined by enzyme-linked immunosorbent assay. Dorsal abscess formation induced by the injection of viable P. gingivalis was examined daily for 30 days. RESULTS: The footpad swelling of the anti-IL-10-treated group (group 4) was significantly higher than that of groups 1 to 3. Similarly, the serum IFN gamma level in group 4 was much higher than that of the other experimental groups. There was no significant difference in serum IgG antibodies to Pg-LPS in any of the experimental groups. However, the level of IgM antibodies in group 4 mice was significantly lower than that in groups 2 and 3. In addition, serum IgG1 was suppressed in group 4 mice, while IgG2a antibodies were raised. However, there was no difference observed between the levels of IgG2b and IgG3 antibodies in any group of mice. The lesions in sham-immunized mice (group 1) persisted for 30 days, and those in group 2 and 3 were undetected by day 18 and 20, respectively. In sharp contrast, lesions in group 4 had healed completely by day 13. CONCLUSIONS: This study has shown that IL-10 depletion in vivo in P. gingivalis LPS-induced immune response in mice led to an elevated DTH response, an increase in serum IFN-gamma levels, and raised levels of IgG and IgG2a antibodies. Treatment with anti-IL-10 antibodies resulted in suppressed IgG1 and IgM responses and a more rapid healing of abscesses than in non-IL-10-depleted mice. These results suggest that IL-10 depletion in Pg-LPS-induced immune response in mice may lead to a Th1-like immune response and provide strong protection against a subsequent challenge with live P. gingivalis in an abscess model. PMID- 11759865 TI - Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. AB - BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients. PMID- 11759866 TI - Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. AB - BACKGROUND: Impaired polymorphonuclear neutrophil (PMN) functions were generally considered to be related to the onset of generalized aggressive periodontitis (GAgP). However, some research has indicated that the hyperreactivity of PMN seems to be involved in the inflammatory response of GAgP. The present study's main purpose was to provide more evidence about the role of PMN in the pathogenesis of GAgP by surveying PMN infiltration in gingiva and its relationship with the expression of their mediators including intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). The inflammatory response in GAgP was also compared with that in adult periodontitis (AP) and periodontally healthy subjects. Since these PMN mediators were reported to be produced mainly by macrophages, the association between the expression of these PMN mediators and the distribution of macrophages was also investigated. METHODS: A total of 25 gingival specimens were obtained from 10 GAgP patients, 10 AP patients, and 5 periodontally healthy subjects. Serial sections were obtained from each specimen, and the following techniques were adopted to investigate the distribution and interrelation of different cells and cytokines. Infiltration of PMN was observed by using hematoxylin and eosin staining. Distribution of the macrophages, identified as CD68+, was shown by using immunohistochemistry. Immunohistochemistry and in situ hybridization were used to detect the expression of ICAM-1, IL-8, IL-1beta, and TNF-alpha in gingival tissues. These techniques were performed in serial sections from each individual specimen. RESULTS: Large numbers of infiltrating PMNs were observed in gingiva from GAgP. In gingiva from both GAgP and AP, the strongest protein and mRNA expression of IL-8, ICAM-1, IL 1beta, and TNF-alpha were located in pocket epithelium and adjacent connective tissue with large numbers of infiltrating PMNs. In tissues without abundant PMN infiltration, the appearance of positive cells expressing IL-8, ICAM-1, IL-1beta, and TNF-alpha was scattered. CD68+ was distributed sparsely in connective tissue and was hardly seen in pocket epithelium with large numbers of PMN infiltration. The degree of leukocyte infiltration and connective tissue destruction in gingiva from GAgP patients was not distinctly different from that in gingiva from AP. The gingival specimens with heavy PMN infiltration from both GAgP and AP patients presented strong expressions of IL-1beta and TNF-alpha; showed more extensive inflammatory cell infiltration; had severe connective tissue destruction; and presented severe elongation and ulceration of pocket epithelium. In gingiva from healthy subjects, inflammation was minor with visually no PMN, CD68+, or the positive cells of IL-8, ICAM-1, IL-1beta and TNF-alpha expression. CONCLUSIONS: Enhanced accumulation of PMN, which is associated with the upregulation of IL-8, ICAM-1, IL-1beta, and TNF-alpha expression, relates to the severity and activity of GAgP. In addition to macrophages, PMN and/or epithelial cells might also be important sources of IL-8, IL-1beta, and TNF-alpha production in gingiva. PMID- 11759867 TI - Analysis of single nucleotide polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in Japanese patients with early-onset periodontitis. AB - BACKGROUND: Early-onset periodontitis (EOP) is considered to have a genetic basis, which has not been clearly defined. The tumor necrosis factor-alpha (TNF alpha) gene polymorphism as one of the genetic factors may influence the expression of several chronic inflammatory diseases. The aim of the present study was to evaluate whether the polymorphisms in the 5'-flanking region of the TNF alpha gene are associated with Japanese EOP patients. METHODS: Forty-six Japanese, generalized EOP (G-EOP) patients and 104 Japanese healthy subjects were identified according to established clinical criteria. Twenty healthy subjects were analyzed by nucleotide sequence to screen polymorphisms of the 5'-flanking region of the TNF-alpha gene. Then, all subjects were analyzed by polymerase chain reaction and sequence-specific oligonucleotide probe (SSOP) methods. RESULTS: We determined 5 single nucleotide polymorphisms at positions -1031 (T/C), -863 (C/A), -857 (C/T), -308 (G/A), and -238 (G/A) in the 5'-flanking region of the TNF-alpha gene. There were no significant differences in the genotype and allele frequency when we compared G-EOP patients to healthy subjects. Because the frequency of polymorphic alleles at positions -308 and -238 was very low in this study population, we demonstrated the existence of 4 detected haplotypes and 6 detected genotypes concerning 3 single nucleotide polymorphisms (-1031, -863, and -857). The frequency of the H1/H3 (TCC/TCT) detected genotype tended to decrease in G-EOP patients compared to healthy subjects, but was not statistically significant. CONCLUSION: These findings suggest there is no significant association between polymorphisms in the 5' flanking region of the TNF-alpha gene and susceptibility to G-EOP in Japanese patients. PMID- 11759869 TI - Root coverage and pocket reduction as combined surgical procedures. AB - BACKGROUND: One of the main objectives of periodontal reconstructive surgery is the coverage of exposed roots due to gingival recession. A large variety of mucogingival grafting procedures are available that give highly predictable and esthetically acceptable results when treating intact root surfaces. However, these procedures call for a second surgery site in the palate. The present study examines a series of cases in which connective tissue, obtained from the tuberosity during pocket reduction procedures in the posterior region of the maxilla, was used for root coverage. METHODS: Forty-four teeth from 25 patients with gingival recession of 3.30 +/- 0.14 mm (mean +/- SEM) were treated with subepithelial connective tissue grafts using connective tissue obtained from the tuberosity area during pocket reduction procedures in the posterior region of the maxilla. RESULTS: The mean root coverage recession after treatment was 0.16 +/- 0.06 mm, with effectiveness of coverage at 95.0% +/- 1.84 and a predictability of 84.1%. Periodontal probing depth reduction at the donor site was 4.08 +/- 0.24 mm. CONCLUSIONS: These results indicate that the subepithelial connective tissue graft obtained from the tuberosity area during pocket reduction procedures in the posterior region of the maxilla provides a very predictable and esthetic root coverage without the need for a second surgical site. PMID- 11759868 TI - Immediate implantation in fresh extraction sockets. A controlled clinical and histological study in man. AB - BACKGROUND: Early implantation may preserve the alveolar anatomy, and the placement of a fixture in a fresh extraction socket helps to maintain the bony crest. Although a number of clinical studies exist, no histological reports show the outcome of implantation in fresh extraction sockets without the use of membranes in humans compared to implants placed in mature bone. METHODS: Forty eight healthy patients, receiving at least 4 fixtures in each of 2 symmetrical quadrants, underwent placement of 1 experimental fixture placed in a fresh extraction socket (TI) and 1 contralateral fixture in mature bone (CI). TI were placed after atraumatical tooth extraction, with a surgical site at the apex of the socket and a tight contact between the fixture and the socket's walls, but without the use of filling materials or membranes. The flap was coronally repositioned to obtain primary wound closure. Immediately after surgical intervention, a standardized periapical radiograph was taken. Second-stage surgery was done after 6 months. Six months after the second surgery, a second standardized periapical radiograph was taken and clinical parameters (bleeding and plaque index) recorded. Marginal bone loss (MBL) from the time of implant placement to the time of fixture removal was calculated by comparing periapical radiographs. TI and CI were then removed by a hollow drill to obtain histological specimens. Non-demineralized sections were stained by acid fuchsin and toluidine blue, and by von Kossa to evaluate the degree of bone mineralization. The percentage of direct implant-bone contact (DBC) was calculated by a computerized microscopic digitizer. RESULTS: No significant differences in the clinical and radiographic parameters were observed between the 2 experimental categories. There was no statistically significant difference between TI and CI for DBC either in the maxilla or in the mandible. No connective or fibrous tissues were present around TI or CI. Bone resorption was not present in any of the histological sections. CONCLUSIONS: The present study shows that when a screw type dental implant is placed without the use of barrier membranes or other regenerative materials into a fresh extraction socket with a bone-to-implant gap of 2 mm or less, the clinical outcome and degree of osteointegration does not differ from implants placed in healed, mature bone. PMID- 11759870 TI - A comparison of porous and non-porous teflon membranes plus demineralized freeze dried bone allograft in the treatment of class II buccal/lingual furcation defects: a clinical reentry study. AB - BACKGROUND: The aim of this 9-month reentry study was to compare the regenerative healing using porous (P) and non-porous (NP) teflon barrier membranes plus demineralized freeze dried bone allografts (DFDBA) in Class II buccal/lingual furcation defects. METHODS: Twenty-four patients, 13 males and 11 females, ages 38 to 75 (mean 54 +/- 10), were included in this study. Each patient had adult periodontitis and one Class II furcation defect measuring > or = 3 mm open horizontal probing depth. Twelve patients were randomly selected to receive the NP treatment and 12 received the P membrane. All defects received a DFDBA graft. Measurements were performed by a masked examiner. RESULTS: No statistically significant differences (P>0.05) were found between NP and P groups at any time with respect to any open or closed measure. Improvement in mean open horizontal probing depth was significant for both the NP (2.33 +/- 0.78 mm) and P (2.75 +/- 0.75 mm) groups. Mean clinical attachment level gains at 9 months were significant for both NP (1.50 +/- 1.62 mm) and P (2.50 +/- 2.11 mm) groups. Seventeen of 24 defects had an intrabony component and > or = 50% fill was obtained in 100% of these defects. CONCLUSIONS: The results of this 9-month reentry study comparing the use of porous and non-porous barrier membranes with a DFDBA graft indicate that there were no statistically significant differences between groups. Both groups showed a statistically significant improvement following the treatment of Class II furcation defects in humans. PMID- 11759871 TI - Tetracycline modulates collagen membrane degradation in vitro. AB - BACKGROUND: Structural integrity of implanted bioabsorbable barrier membranes should be preserved for a sufficient time to ensure expected results. Collagen membranes are degraded by metalloproteinases (MMP). Their degradation rate can be altered either by enhancing structural integrity or by delaying the degradation process using MMP inhibitors. Tetracyclines (TTC) present inhibitory effects on matrix MMP. Immersing membranes in TTC solution before implantation can delay their degradation. The purpose of the present study was to evaluate the effect of collagen membranes immersed in varying TTC concentration solutions on the rate of their degradation in vitro. METHODS: Collagen bioabsorbable membranes were prepared as 5 mm diameter membrane discs. Membranes were then incubated at 4 degrees C for 24 hours, in either phosphate buffered saline (PBS, Ca2+ and Mg2+ free) or with TTC-HCl dissolved in PBS concentrations of 5 mg/ml, 50 mg/ml or 100 mg/ml. After rinsing, membranes were incubated with either bacterial collagenase or cultures of human bone lineage cells. Membrane degradation was studied on days 2, 4, 7, and 14. Two- and 3-way analysis of variance was used to analyze results. RESULTS: Samples supplemented with bacterial collagenase exhibited a statistically significant interaction between changes of free protein in the medium, antibiotic concentration used for the immersion, presence of collagenase in the medium, and incubation time (P<0.0001). Membranes incubated with bone cells exhibited similar degradation trends. CONCLUSIONS: Collagen membranes immersed in 50 mg/ml TTC solution exhibited the longest degradation time, both in the clostridial collagenase and the human bone cell lineage assays. Immersion in a 50 mg/ml TTC solution before implantation will delay their degradation. PMID- 11759872 TI - Activation of matrix metalloproteinase-2 by a novel oral spirochetal species Treponema lecithinolyticum. AB - BACKGROUND: Periodontal tissue destruction is a characteristic of periodontitis. This can be caused by either bacterial enzymes or host cell-derived matrix metalloproteinases (MMPs). In order to elucidate the etiologic role of oral spirochetes, we investigated the effects of Treponema lecithinolyticum, a novel saccharolytic species, on MMP-2 activation. METHODS: Gingival fibroblasts (GFs) and periodontal ligament (PDL) cells obtained from healthy human subjects were cultured to confluence in alpha-minimal essential medium (alpha-MEM) supplemented with 10% fetal bovine serum. After serum starvation for a day, the cultures were treated with whole cell sonicates, heat-denatured whole cell sonicates, outer membrane fraction (OMF) or formaldehyde-fixed cells of T. lecithinolyticum. Culture supernatants were collected after incubation for 24 to 48 hours and analyzed for MMP-2 activation by gelatin zymography. Collagenolytic activity was quantitatively measured using human [3H] type IV collagen as a substrate. RESULTS: Treatment of GFs and PDL cells with whole cell sonicates, formaldehyde fixed whole cells, or the OMF of T. lecithinolyticum resulted in the production of MMP-2 partly in the fully active form with a molecular mass of 62 kDa, whereas non-treated control cultures and cultures treated with a heat-denatured fraction did not show the active form. Cultures exposed to T. lecithinolyticum had higher collagenolytic activity than non-treated cultures. CONCLUSIONS: Our results demonstrate that T. lecithinolyticum, possibly mediated by proteinaceous cell surface-associated components, may participate in extracellular matrix degradation by activation of MMP-2 during periodontal inflammation. PMID- 11759873 TI - Aggressive periodontitis associated with Fanconi's anemia. A case report. AB - BACKGROUND: Fanconi's anemia is an autosomal recessive disease associated with chromosomal breakage as well as pancytopenia, skin pigmentation, renal hypoplasia, cardiac defects, microcephaly, congenital malformations of the skeleton, hypogonadism, and increased risk of leukemia. The present report describes the periodontal clinical and microbiological status of an 11-year old male having Fanconi's anemia. METHODS: Polymerase chain reaction analysis to detect human cytomegalovirus (HCMV), Epstein-Barr type 1 virus, and herpes simplex virus (HSV) was performed on paper-point samples pooled from either 3 periodontal sites with advanced attachment loss or 3 gingivitis sites with no clinical attachment loss. Anaerobic bacterial culture examination was performed on the pooled periodontitis sample. RESULTS: The patient suffered from pancytopenia, allergy, asthma, hearing impairment, and mental retardation. Dentition consisted of 7 primary teeth, 11 erupted permanent teeth, and 14 unerupted permanent teeth. Most erupted teeth showed severe gingival inflammation with some gingival overgrowth and various degrees of periodontal attachment loss. Genomes of HCMV and HSV were detected in the pooled periodontitis sample and HCMV in the pooled gingivitis sample. The periodontitis sample but not the gingivitis sample revealed HCMV mRNA of major capsid protein, suggestive of active viral infection. The periodontitis sample also yielded Actinobacillus actinomycetemcomitans (1.1% of total isolates), FusobActerium species (7.9%), Campylobacter species (2.2%), Peptostreptococcus micros (3.4%), and Candida albicans (0.3%). CONCLUSIONS: Oral features of Fanconi's anemia may include increased susceptibility to periodontitis. It is likely that underlying host defense impairment coupled with periodontal infection by HCMV and A. actinomycetemcomitans contribute to the severe type of periodontitis associated with Fanconi's anemia. PMID- 11759874 TI - Histology of connective tissue graft. A case report. AB - BACKGROUND: Few investigations can be found in the literature on the histological nature of the attachment of connective tissue grafts to root surfaces previously exposed by recession. METHODS: In this case report, a 24-year-old patient was treated with a connective tissue graft combined with a partial-thickness coronally positioned flap for root coverage of Class I Miller recessions at the maxillary right and left canines and first premolars. The treated sites exhibited 83% and 100% root coverage on the right and left sides, respectively. Twelve months later, the case required extraction of all 4 first premolars for orthodontic reasons. Two conservative block sections including the maxillary first premolars with the buccal soft tissues were obtained and processed histologically in a bucco-palatal plane. RESULTS: Histological analysis showed that healing occurred via a long junctional epithelium throughout the major portion of the previous recession site. Only minimal signs of new cementum-like tissue formation could be seen in the apical portion of the recession area coronal to the base of the instrumented root surface. No root resorption or ankylosis could be detected in any of the serial sections. CONCLUSIONS: The findings of this case report outline the possible variations in the histological outcome of connective tissue grafts. These variations can be attributed to differences in size and shape of the recession defects and flap positioning at the end of surgery. PMID- 11759875 TI - Observations on a new collagen barrier membrane in 16 consecutively treated patients. Clinical and histological findings. AB - BACKGROUND: Space-maintaining capacity, cell disclusive potential, and stability over time are crucial factors to achieving sufficient bone augmentation with membrane barriers. The case series presented here assessed a new collagen barrier used in bone augmentation. Clinically, the healing pattern, especially in cases of secondary healing, was studied. METHODS: Soft tissue healing was documented by photographs, and the size of the dehiscences calculated by image analysis. The measurements were performed on digitized photographs. During reentry, barrier remnants were dissected and histologically evaluated. RESULTS: The mean value for dehiscences was 35.5 mm2; all dehiscences healed within 4 weeks after the exposure became evident. The difference was statistically significant between the week 2 and week 6 visits (P = 0.008) for each previously exposed site. The histologic observation of barrier remnants revealed direct apposition of fibrous and bone tissues on the membrane surface. CONCLUSION: In cases of membrane exposure, gingival dehiscences always disappeared in the following weeks without affecting the healing process. Histologic results showed barrier stability over a 6-month period, promoting bone regeneration. PMID- 11759876 TI - Position paper: Guidelines for periodontal therapy. AB - The American Academy of Periodontology offers the following Guidelines for Periodontal Therapy. These guidelines are intended to fulfill the Academy's obligation to the public and to the dental profession. This paper sets forth the clinical objectives and scope of periodontal therapy. These guidelines are designed to give guidance to state legislatures and agencies that regulate the practice of periodontology and should be considered in their entirety. PMID- 11759877 TI - Serial measurement of arterial lactate concentrations as a prognostic indicator in relation to the incidence of disseminated intravascular coagulation in patients with systemic inflammatory response syndrome. AB - To demonstrate the prognostic value of measuring blood lactate concentrations and to investigate the mechanisms of lactate production in patients with systemic inflammatory response syndrome (SIRS), we conducted a prospective cohort study. Among 22 patients with SIRS, there were 9 survivors and 13 nonsurvivors. Serial arterial lactate concentrations were measured on the day of admission to the intensive care unit (day 0). then on days 1-4. The subjects of this study consisted of 14 patients with SIRS, 6 with severe sepsis, and 2 with septic shock. On admission, the lactate concentrations did not differ between the two groups, but remained high in the nonsurvivors throughout the study period, while they progressively decreased in the survivors. The incidence of disseminated intravascular coagulation (DIC) was significantly higher in the nonsurvivors than in the survivors. The nonsurvivors had persistently higher DIC scores and lower platelet counts than the survivors. The changes in lactate concentration over time were statistically different between the patients with DIC and those without DIC. The findings of this study clearly demonstrated that serial arterial lactate measurements can predict a poor outcome in patients with SIRS, severe sepsis, or septic shock. DIC might play an important role in the pathogenesis of lactate production in these newly defined critically ill patients. PMID- 11759878 TI - Prediction of the postoperative pulmonary function and complication rate in elderly patients. AB - We analyzed the risk factors predisposing elderly patients to develop postoperative respiratory complications (PRCs) and investigated the possibility of predicting the postoperative pulmonary function and PRC rate. The postoperative pulmonary functions were predicted according to a simplified system, which we developed using plain chest roentgenograms from patients with primary lung cancer. Both univariate and multivariate analyses of PRCs were performed in 39 elderly patients with lung cancer from July 1982 to March 1991 (the early period). Based on the results obtained, the permissible extent of lung resection to achieve a predicted postoperative % forced expiratory volume in 1 s (ppo%FEV1.0) and a predicted postoperative % vital capacity (ppo%VC) of more than 55% was selected as the basic criteria for undergoing such an operation after April 1991 (the recent period). A ppo%FEV1.0 and/or ppo%VC of 55% or less was the most significant risk factor for developing PRCs. The PRC rate decreased from 33.3% to 9.8% (P = 0.0251) and the operative mortality rate decreased from 10.3% to 0%. The survival rates for stage I, II. and III cases were not significantly different between the early and recent periods. Decisions made on the operability and the permissible extent of lung resection based on our system using plain chest roentgenograms therefore appeared to reduce the PRC rate and operative mortality rate in elderly patients. PMID- 11759879 TI - Long-Term surgical outcomes following intraluminal sutureless graft insertion for type A aortic dissection. AB - The long-term outcome of sutureless intraluminal graft insertion remains unclarified. Therefore, we reviewed the late surgical outcomes of patients who underwent this procedure for acute type A dissection. Between March 1990 and May 2000, 80 patients aged from 36 to 92 years underwent isolated replacement of the ascending aorta for type A acute aortic dissection. The surgical procedures performed were replacement with an intraluminal sutureless graft in 18 patients (group 1) and suturing of the aorta with a conventional Dacron prosthesis in 62 patients (group 2). The cross-clamp, extracorporeal circulation, circulatory arrest, and operation times were significantly shorter in group 1 than in group 2, and the amount of total blood transfusion was also significantly less in group 1 than in group 2. The hospital mortality rates were 11.1% (2/18) in group 1 and 9.7% (6/62) in group 2 (P > 0.999). The 5-year actuarial survival rates (including operative mortality) were 71% +/- 11% in group 1 and 77% +/- 9% in group 2 (P = 0.268). The event-free survival rates at 5 years were 80% +/- 10% in group 1, and 67% +/- 13% in group 2 (P = 0.780). Regarding graft-related complications, long-term follow-up revealed one graft-related death and one reoperation in group 1 (12.5%), and no graft-related complications in group 2 (0%) (P = 0.047). In conclusion, intraluminal sutureless grafts required less blood transfusion, and shorter cross-clamp, extracorporeal circulation, circulatory arrest, and surgery times. However, the procedure did not improve the hospital mortality or long-term outcome. In fact, the rate of graft-related complications was significantly higher in the intraluminal sutureless group than in the sutured group. Therefore, the intraluminal graft insertion technique should be used only under exceptional circumstances. PMID- 11759880 TI - Multiple primary cancers associated with esophageal carcinoma. AB - This study was conducted to examine the characteristics of esophageal cancers with primary synchronous or metachronous cancer in another organ. We retrospectively evaluated 744 patients who underwent esophagectomy for esophageal cancers between 1985 and 1998. The patients were divided into two groups according to whether they had multiple primary cancer (MPC) or nonmultiple primary cancer (NPC). Stage I cancer was significantly more frequent among patients with MPC than among those with NPC (P < 0.0001). Among patients with MPC, another primary cancer was found in the head and neck region in 70 (42.4%), in the stomach in 51 (30.9%), and in the colon, lung, breast, and other locations in the remaining patients. Of the 70 patients with another primary cancer in the head and neck region, 32 (45.7%) had pharyngeal cancer. Furthermore, the incidence of intraesophageal multiple cancer in the patients with primary cancer in the head and neck region was significantly higher than that in those whose other primary cancers were gastric cancer or in those with NPC (P = 0.0135. P < 0.0001). The 5-year survival rate of the patients with MPC was 51.28%, which was significantly higher than that of those with NPC (P = 0.019). In conclusion, a better knowledge of the relationships between esophageal carcinoma and cancers in other organs may lead to earlier detection of other primary cancers and improved therapeutic results. PMID- 11759881 TI - Cholecystocholangiography during laparoscopic cholecystectomy. AB - The aim of this study was to assess the efficacy and safety of performing cholecystocholangiography through a central venous pressure catheter during laparoscopic cholecystectomy. Laparoscopic cholecystocholangiography was attempted during laparoscopic cholecystectomy for chronic calculous cholecystitis in 40 patients, and considered successful if the biliary anatomy was clearly defined. The procedure was evaluated as successful in 36 patients (90%). It added an average 13.5 min to the operating time. A unsuspected common bile duct stone was identified by cholecystocholangiography in one patient and there were no cholangiogram-related complications. We concluded that laparoscopic cholecystocholangiography is a safe, simple, and quick procedure that can be used as an alternative to cystic duct cholangiography to identify the biliary anatomy and detect any common bile duct calculi prior to laparoscopic dissection. PMID- 11759882 TI - Intra-abdominal extrahepatic echinococcosis. AB - Twenty-seven patients who were treated surgically because of extrahepatic abdominal hydatid disease between 1981 and 1999 were retrospectively reviewed. Nineteen patients had coexistent hepatic cysts while 8 patients had only peritoneal cysts. The cysts were located in the spleen, pancreas, adrenal gland, mesentery of the intestines, ovaries, retroperitoneum, omentum, abdominal wall, rectovesical region, and the psoas muscle. Due to organ destruction because of large cysts in 8 patients, the involved organ had to be sacrificed. The other 19 patients were treated by a pericystectomy. No postoperative mortality or severe morbidity was seen. In conclusion, symptomatic or large cysts should be surgically treated. In cases suspected of having peritoneal spillage, antihelminthic drugs should be administered. In addition, small asymptomatic cysts may also be effectively treated with antihelminthics. PMID- 11759883 TI - Vascular relaxant effects of toborinone on the isolated canine internal mammary artery. AB - This study was conducted to evaluate the vascular relaxant effects of toborinone on canine internal mammary ring preparations. We determined the concentration contraction curves for various vasoconstrictors, namely norepinephrine, serotonin, U46619, endothelin-1, phenylephrine, and KCl in internal mammary artery (IMA) preparations, then assessed the vascular relaxant effects of the test drugs. As models, preparations with and without functional endothelium were used. As vasorelaxants, we used milrinone, papaverine, and nitroglycerin. Toborinone produced concentration-dependent relaxation in preparations precontracted with norepinephrine and serotonin. However, the vascular relaxant effect of toborinone on KCl-induced contraction was weaker than those on norepinephrine- and serotonin-induced contraction. Toborinone produced concentration-dependent relaxation in preparations with, and those without functional endothelium. There was no difference in the potency between the preparations with, and those without functional endothelium. The relaxing effect of toborinone on norepinephrine-induced contraction (EC50 = 1.3 x 10(-6) M) was significantly weaker than that of nitroglycerin (EC50 = 7.8 x 10(-8) M), equal to that of papaverine (EC50 = 2.2 x 10(-6) M), and significantly stronger than that of milrinone (EC50 = 3.3 x 10(-6) M). These results demonstrate that toborinone produces relaxant effects on canine IMA preparations, and that it may be effective in the treatment of IMA malperfusion syndrome. PMID- 11759884 TI - Effect of cilostazol on endothelial cell denudation and proliferation in canine vein grafts. AB - The purpose of the present study was to examine the effects of cilostazol on endothelial cell denudation and proliferation in vein grafts used as arterial substitutes. Unilateral aortoiliac bypass was performed using the lateral jugular vein in 20 mongrel dogs. The animals were divided into two groups according to whether or not cilostazol was given. The grafts were removed at intervals of 1 day and 50 days, and the luminal surface was assessed for endothelial cell coverage (%). The denudation of endothelial cells was less extensive in the cilostazol group than in the control group on postoperative day 1. There was significantly more proliferation of endothelial cells in the control group over the course of time than in the cilostazol group. In conclusion, cilostazol significantly prevented early endothelial cell denudation, although it did not appear to stimulate successive endothelial cell proliferation. Therefore, cilostazol may help preserve an intact intima, which would potentially result in the inhibition of intimal hyperplasia. PMID- 11759885 TI - Metachronous primary hyperparathyroidism due to a parathyroid adenoma and a subsequent carcinoma: report of a case. AB - An extremely rare case of metachronous primary hyperparathyroidism (PHP) due to a parathyroid adenoma and subsequent carcinoma with local lymphatic spread is presented herein. A 55-year-old woman was operated on for a parathyroid adenoma in the right inferior gland. Thirteen years after the first operation, she was again hospitalized for hypercalcemia and the presence of a hard mass in the right anterior neck region. Exploratory surgery and a histological examination of the resected tumor provided evidence of a parathyroid neoplasm in the right superior gland but the malignancy was equivocal. Postoperatively, her serum parathyroid hormone (PTH) level remained at 1.5-fold the upper limit of the normal range, and hypercalcemia again gradually developed. The results of higher positive rates by Ki-67 immunohistochemical staining and an aneuploid pattern by a flow cytometric analysis of the second neoplasm were consistent with a histological diagnosis of carcinoma, and she therefore underwent further surgery. A radical neck dissection revealed two lymph node metastases which were both successfully removed. The postoperative serum PTH and calcium levels then returned to within the normal ranges. These findings indicate the usefulness of Ki-67 immunohistochemical staining and a flow cytometric analysis for differentiating malignant lesions from benign parathyroid lesions, and the importance of surgically treating cases limited to local regions without distant metastasis. PMID- 11759886 TI - Malignant adenomyoepithelioma of the breast with lung metastases: report of a case. AB - Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86 year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases. PMID- 11759887 TI - Reoperative coronary artery bypass grafting via a left thoracotomy and a small laparotomy without cardiopulmonary bypass: report of a case. AB - A 66-year-old woman with aortic stenosis underwent an aortic root replacement with a composite graft and coronary artery reconstruction 2 years before presentation. On coronary angiography performed 2 years after operation, saphenous vein graft (SVG) to right coronary artery and SVG to first diagonal branch had both become totally occluded. SVG to left anterior descending artery showed 75% stenosis on the heel side of the distal anastomosis. The patient underwent a second coronary artery bypass via a left thoracotomy (the left internal thoracic artery was anastomosed to the first diagonal branch by interposing it with the left radial artery) and a small laparotomy (the right gastroepiploic artery was anastomosed to the right coronary artery) without a cardiopulmonary bypass. This approach is preferable to avoiding both a resternotomy and cardiopulmonary bypass in patients requiring repeat surgery. PMID- 11759888 TI - Ruptured cardiac hydatid cyst masquerading as acute coronary syndrome: report of a case. AB - The case of a 40-year-old man hospitalized for investigation of a doubtful diagnosis of acute coronary syndrome is reported herein. Two-dimensional echocardiography and angiography showed a cardiac cyst localized in the left ventricular apex in close proximity to the left anterior descending coronary artery. Surgery performed with the aid of cardiopulmonary bypass revealed that the cyst had ruptured partially into the left ventricle and filled with thrombus. This case is of particular interest because of the rarity of cardiac localization of a hydatid cyst, and the conflict between the severity of the complications that occurred and the absence of correlated symptoms. PMID- 11759889 TI - Successful surgical treatment of a ruptured abdominal aortic aneurysm without homologous blood transfusion in a Jehovah's Witness: report of a case. AB - We report herein the case of a 47-year-old woman of the Jehovah's Witness faith in whom Y-grafting for a ruptured abdominal aortic aneurysm was successfully performed without a homologous blood transfusion. We used a Cell Saver (Haemonetics, Braintree, MA. USA) red cell salvaging device and an aortic occlusion balloon catheter, and performed gentle and minimal dissection during the operation. Postoperatively. the patient was kept heavily sedated and required hypothermic therapy for only 14h. We treated her severe anemia using conventional drugs, including iron and folic acid, and her hemoglobin increased smoothly. Although her hemoglobin level decreased to 2.8g/dl during the operation, her postoperative course was uneventful. PMID- 11759890 TI - Alpha-Fetoprotein-producing esophageal adenocarcinoma: report of a case. AB - Alpha-fetoprotein (AFP)-producing esophageal tumors are extremely rare. We report herein the case of a 51-year-old man found to have an AFP-producing adenocarcinoma arising from esophageal proper mucosa. The patient presented for investigation of dysphagia, and esophagogram and endoscopy revealed a lesion about 2 cm in size with a depressed center surrounded by low nodular protrusions in the lower esophagus. The preoperative serum AFP concentration was elevated to 52.4 ng/ml. A subtotal esophagectomy was performed, and macroscopic examination of the resected specimen revealed a superficial protruding lesion. Histopathological studies showed a poorly differentiated adenocarcinoma with a single lymph node metastasis. The tumor had infiltrated the submucosal layer, but there was no evidence of lymphatic or venous invasion. Immunohistochemical study revealed tumor cells positive for AFP. There were no findings of Barrett's epithelium or any mucosal changes due to reflux esophagitis. An elevated AFP level 2 years after the operation led us to suspect tumor recurrence; however, diagnostic imaging studies showed no evidence of a recurrence or metastases. The serum AFP levels responded well to chemotherapy with transient decreased levels, but continued to rise until finally, 5 years after the operation, adenocarcinoma cells were detected in the pleural effusion. Thus, careful monitoring of the serum AFP levels at regular intervals could be a useful marker to indicate recurrence of esophageal carcinoma. PMID- 11759891 TI - Isolated mesosigmoidal hydatid cyst as an unusual cause of colonic obstruction: report of a case. AB - We report herein an unusual case of primary mesosigmoidal hydatid cyst that presented as acute left colonic obstruction mimicking sigmoid colon cancer. A 61 year-old man with a 3-day history of abdominal pain, distention, obstipation, vomiting, and fever was admitted to the emergency department of our hospital. Surgery was performed under a presumptive diagnosis of acute left colonic obstruction. The intraoperative findings were highly suggestive of sigmoid colonic carcinoma and Hartmann's procedure was performed. Histopathological examination of the pathological specimen revealed an isolated hydatid cyst embedded in mesosigmoid which had caused mechanical sigmoidal obstruction. Primary extrahepatic, intra-abdominal localization of a hydatid cyst is not unusual. Therefore, as a hydatid cyst may cause a wide variety of clinical syndromes, it should be kept in mind in the differential diagnosis of mechanical bowel obstruction, especially in endemic regions. PMID- 11759892 TI - Segmental intestinal preservation and enteral nutrition help to maintain the intestinal function after a massive intestinal resection: report of a case. AB - We report a case in which both segmental intestinal preservation and enteral nutrition helped to maintain the intestinal function after a massive bowel resection for superior mesenteric artery (SMA) thrombosis. A 53-year-old Japanese man was admitted to our hospital with acute abdomen. Extensive necrosis of the small intestine was found during the operation; however, a loop of the ileum appeared to be viable. A massive resection of the small intestine which preserved a 50-cm length of the viable ileum loop was thus performed. However, diffuse stenosis of the remaining ileum was found after surgery. An end-to-end anastomosis of the distal end of the preserved ileum loop and the terminal ileum was made in the second operation, and enteral nutrition was infused to improve the remnant intestinal function. A jejunoileostomy was performed in the final operation. An X-ray study after the final operation showed the stenosis of the remaining ileum to have improved. The patient therefore did not need any nutritional support after being discharged. PMID- 11759893 TI - Duodenal pancreatic heterotopy diagnosed by magnetic resonance cholangiopancreatography: report of a case. AB - We describe herein the case of a heterotopic pancreas that caused stenosis in the second portion of the duodenum. A 46-year-old man presented with upper abdominal pain and a 12-month history of intermittent vomiting. There was no history of melena, hematochezia, hematemesis, clay-colored stools, jaundice, or hepatitis and he did not describe any food dyscrasias, although fatty foods and alcohol seemed to make the symptoms worse. No specific medication or change in position relieved the pain. An initial diagnosis of chronic pancreatitis with multiple pseudocysts was made on the basis of elevated serum amylase and lipase levels, and abdominal ultrasonography and computed tomography (CT) findings. Medical treatment with octreotide was given for 8 weeks, but without any marked effect. Double-contrast barium examination and esophagogastroduodenoscopy were not diagnostic. Magnetic resonance (MR) cholangiopancreatography revealed findings indicative of cystic dystrophy of a heterotopic pancreas (CDHP), and an endoscopy supported this diagnosis. A pancreatoduodenectomy was performed and pathological examination confirmed a diagnosis of CDHP. In our opinion, MR cholangiopancreatography is the diagnostic tool of choice when CDHP is suspected. PMID- 11759894 TI - Delayed rupture of a pseudoaneurysm following pancreatoduodenectomy: report of a case. AB - We report herein the case of a 63-year-old man in whom delayed rupture of a pseudoaneurysm occurred 120 days following pancreatoduodenectomy. Color Doppler examination indicated a pseudoaneurysm originating from the ligated gastroduodenal artery. Transcatheter arterial embolization was done at the common hepatic artery, proximal and distal to the pseudoaneurysm, with microcoils. The patient had a minor elevation of liver enzymes, which subsequently returned to normal. Due to the absence of any postoperative complications such as pancreatic anastomotic leakage, we assumed that the pseudoaneurysm formation had been caused by a weakness in the arterial wall according to skeletonization resulting from lymphadenectomy and intraoperative radiation therapy. To our knowledge, this case represents the longest interval between pancreatoduodenectomy and rupture of a pseudoaneurysm ever to be reported in the literature. PMID- 11759895 TI - Expression of the prothymosin-a gene as a prognostic factor in lung cancer. AB - Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis. PMID- 11759896 TI - Gasless endoscopic thyroid and parathyroid surgery using a new retractor. AB - Endoscopic thyroid and parathyroid surgery have now become feasible procedures, but the working space provided by the gasless technique is more limited than that of the CO2 insufflation technique. Gasless endoscopic surgery was performed in 20 patients with thyroid or parathyroid tumors. A newly designed retractor was used. Gasless endoscopic surgery was performed in all patients without conversion to conventional techniques. The recurrent laryngeal nerve was visualized and preserved in all patients. No recurrent nerve palsy was noted. The new retractor created a sufficient working space, and our results demonstrated the feasibility of this technique. PMID- 11759897 TI - Videolaparoscopy with omentopexy: a new technique to allow placement of a catheter for continuous ambulatory peritoneal dialysis. AB - Malfunction of a peritoneal dialysis (PD) catheter is common and usually occurs shortly after its insertion, due to omental wrapping. In fact, we have encountered this complication in 183 of 578 (31.6%) patients treated at our hospital since 1987. To overcome this problem, I have devised a new laparoscopic technique for catheter insertion. First, the omentum is fixed onto the peritoneum of the lateral abdominal wall at two points using a laparoscopic instrument (Pro Tack 5-mm Auto Suture, Norwalk, CT, USA) placed at the level of the umbilicus. The catheter is then introduced through the umblical trocar deep into the true pelvis. The cuff is positioned between the posterior rectus sheath and the rectus fibers, and the fascia is sewn. The catheter is then pulled through the 5-mm trocar site. This technique was successfully performed on ten patients with a median age of 46.1 years. There was no morbidity or any malfunction in continuous ambulatory peritoneal dialysis (CAPD) during follow-up periods ranging from 20 days to 9 months. Therefore, this new laparoscopic technique may prevent the obstruction caused by omental wrapping in CAPD. PMID- 11759898 TI - The use of needlescopic instruments in laparoscopic ventral hernia repair. AB - A successful laparoscopic hernia repair requires complete covering of the hernia defect, adequate tension of the prosthesis, and secure stapling with a stapler. We describe herein our technique of performing laparoscopic hernia repair using a needlescopic instrument which results in minimal damage to the abdominal wall and has significant cosmetic benefits. Our technique is easy to perform and useful for achieving initial anchoring of the prosthesis before fixation to the abdominal wall with a laparoscopic stapler. PMID- 11759899 TI - Ammonia removal from compost leachate using zeolite. III. Regeneration of zeolite columns. AB - The effects of hydraulic reteneration time (HRT), and the strength of the regenerating solution on the ammonia adsorption capacity and the zeolite regeneration were studied using bench-scale packed zeolite columns. A 0.6 M NaCl solution fed at a HRT of I h was preferred for the regeneration process, and more than 95% of adsorbed ammonium ions were recovered after using 7-8 bed volumes (BV) of the regenerating solution. The adsorption-regeneration time ratio was approximately 5:1. High concentration of potassium ions in the composting leachate competed with NH4+ ions for the exchange sites, resulting in a reduction in the efficiencies of ammonia removal and zeolite column regeneration. However, Zeolite still proved to have a great potential as a medium for ammonia removal in treating composting leachate. PMID- 11759900 TI - Removal of lead ions by keramzite sand coated with electroplating sludge under dynamic conditions. AB - Column studies were performed to determine the effect of bed height, linear flow rate, adsorbent particle size and initial metal ion concentration on lead removal by keramzite sand coated with electroplating sludge. The Bed depth service time (BDST) model applied to the data at 2% breakthrough gave the best approximation to the experimental results compared with other investigated breakthrough points. The adsorption performance of the thermally modified coated keramzite columns could be well described by the Wolborska model up to 50% breakthrough point. The application of this model allowed determination of the kinetic coefficients of external mass transfer in the fixed bed and the time for protective action of the sorbent layers. The experimental results support the assumption that the external mass transfer of the solute through the hydrodynamic boundary layer is the rate limiting step. It has been established that the keramzite sand coated with electroplating sludge (particle size 0.5-0.8 mm) can be successfully used for lead removal from dilute metal ion solutions at linear flow rate 4-6 cm/min and empty bed contact time > or = 3 min. PMID- 11759901 TI - Enhancing dissipation of aroclor 1248 (PCB) using substrate amendment in rhizosphere soil. AB - Soils contaminated in the laboratory with Aroclor 1248 (PCB) were amended with biphenyl and plant residues that are known to induce PCB degradation, and planted with crops that inherently stimulated PCB dissipation in a previous study to determine if the combination of soil amendment and planting could further enhance PCB dissipation beyond that shown by planting alone. The plants used were flat pea (Lathyrus sylvestris), reed canarygrass (Phalaris arundinacea), and burr medic (Medicago polymorpha). They were grown in laboratory microcosms at a 12h photoperiod in soil containing 50mg/kg PCB. Portions of soil were amended with biphenyl (1,000 mg/kg), ground pine needles, or orange peels (2% w/w), and a portion was left unamended to serve as control. After nearly 100d, PCB recoveries ranged from 69% of initial applications in unplanted soil to 65, 59 and 55% of initial levels in soils that were unamended but planted with flat pea, reed canarygrass and burr medic respectively. PCB recoveries in soils that were amended, but left unplanted ranged from 59% of initial applications in pine needle amended-soil to 48 and 45% in biphenyl- and orange peel-amended soils respectively. Combinations of soil amendment and planting enhanced PCB dissipation in soil compared to planting alone, except the combination of biphenyl amendment and planting with burr medic, where the soil still contained nearly 80% of the initial PCB additions after about 100 d. Estimates of bacterial populations were generally slightly to significantly higher in orange peel and biphenyl-amended soil than in unamended soil, except in biphenyl-amended soil that was planted with burr medic, where bacterial counts were significantly lower than in most of the other treatment combinations. PMID- 11759902 TI - Deposition record of organochlorine pesticides in a sedimentary core in Macao Estuary, Pearl River, China. AB - This paper present the concentration profiles of the organochlorine pesticides in a sediment core from Macao Estuary, Pearl River, China. Concentrations of organochlorine pesticides were determined by GC/ ECD and GC/MSD, and the core was dated by 210Pb method in a content-activity model. The results show that the concentrations of HCHs and DDTs in the core ranged from 0.48-26.3 and 1.92-39.1 microg/kg, respectively. Concentration of DDTs in the research area was above the Effects Range-Low value (ERL) for Marine and Estuarine sediments. The vertical distributing of organochlorine pesticides in the core was influenced by the water flux of Pearl River and the pollutants are mainly attributed to the runoff of local agricultural soils. PMID- 11759903 TI - Chemical kinetics of the photocatalytic degradation of trans-cinnamic, dihydrocinnamic, trans-caffeic, and dihydrocaffeic acids. AB - Quantitative studies of the catalysed degradation of aqueous solutions of cinnamic 1, dihydrocinnamic 2, trans-caffeic 3 and dihydrocaffeic 4 acids in the presence of TiO2 and UV radiation at pH 3 and 10 are reported. The phenolic and aliphatic unsaturated groups in caffeic acid 3 caused it to be adsorbed more strongly than the phenolic saturated acid 4, and these two acids were much more strongly adsorbed than cinnamic and hydrocinnamic acids. The kinetics of the degradation of each acid has been studied at pH 3 and 10. TIC analysis showed complete mineralisation of the acids after 9 h. PMID- 11759904 TI - Hydrologic modeling of aquatic plant treatment systems polishing dairy lagoon effluents. AB - In this study, a mathematical model of the hydrologic balance of an aquatic plant treatment system (APTS) has been developed. The mass balance approach has been adopted and the major components of the water balance, such as precipitation, evapotranspiration (ET) and percolation have been incorporated into the model. For estimation of ET for duckweed and water hyacinth plants, mathematical relationships were established between ET and pan evaporation using data collected at the site. The observed ET rates of water hyacinths were up to 66% higher than the pan evaporation rates. But for duckweed, the observed ET rates were 10 to 20% lower than the pan evaporation rates. Using the available historic precipitation and pan evaporation data, several computer simulations of the model were run to estimate the HLR and HRT of the ponds under different design requirements. The results indicate that aquatic ponds with water hyacinths can operate at greater HLR's than ponds supporting duckweed. For a zero discharge system, the allowable HLR for a water hyacinth pond was found to be 5 times that of a pond containing duckweed. PMID- 11759905 TI - Climatic effect on water quality evaluation. AB - An advisory discouraging swimming and other primary contact recreation in Lake Pontchartrain was issued in 1985 by the Louisiana Department of Health and Hospitals (LDHH). The advisory is still in effect today for the south shore area of the lake and names fecal coliform bacteria as the causative pollutant. The suspected source of the contamination in this area is urban stormwater runoff that is collected and pumped to the lake and may be contaminated by sanitary sewer cross-flows. A water quality shoreline study was initiated in the south shore area of the lake in New Orleans by the Department of Civil & Environmental Engineering at the University of New Orleans (UNO). The objective was to determine if the reduced bacteria levels are a result of decreased pollution or if this is a temporary phenomenon caused by a short-term climatic effect. Five monitoring stations were selected for study on the basis of proximity to drainage canals that discharge the stormwater runoff and current or previous use for primary contact recreation. Fecal coliform concentrations was found to be "wet" weather-dependent at all stations except one. There appears to be an active continuous bacteria source near this site since fecal coliform levels there cannot be directly linked to urban runoff. For the remaining areas a general rule of thumb for recreational use of these south shore water is that the user should assume that the water is unsuitable for primary contact recreation, especially in the near vicinity of urban drainage canals, for at least two to three days following a storm event. Precipitation analysis showed a reduction in mean total annual rainfall during the study period amounting to nearly one-third of the typical mean total annual rainfall for the area. Therefore, lower fecal coliform concentrations observed may be due to uncharacteristic drought conditions rather than decreased pollution. PMID- 11759906 TI - Geostatistical based monitoring of soil water NO3- -N: a potential nonpoint source of ground water contamination. AB - Soil water NO3- -N concentrations were monitored for an alfalfa-oat-bean rotation and an alfalfa-bean-bean rotation in the Idaho Snake River Plain as part of the USEPA Section 319 National Monitoring Program. This monitoring study was conducted to evaluate potential beneficial impacts of a USDA recommended crop rotation on subsurface NO3- -N concentrations at a 4.9 hectare (ha) farm test field. Soil water monitoring was conducted in cooperation with the USDA Snake River Plain Water Quality Demonstration Project. Geostatistical and statistical analyses of NO3- -N data collected from a network of soil water solution samplers (lysimeters) coupled with hydrogeological characterization of the field indicated that alfalfa followed by oats reduced soil water NO3- -N concentrations at least temporarily compared to alfalfa followed by beans which is the traditional practice in the area. Soil water NO3- -N sample data showed a unimodal distribution, through the first two months of the split field rotations, that changed to a distinct bimodal distribution three months into the rotations. Development of the bimodal distribution of soil water NO3- -N appeared to correspond directly to the rotational split of the field. The median soil water NO3- -N value calculated from the sample data was approximately 50mgL(-3) greater in the field half planted in beans as compared to the field half planted in oats. Geostatistical spatial mapping results using sequential Gaussian simulations (SGS) supported these findings. SGS results suggested that elevated concentrations of NO3- -N in the soil water were related to both stratigraphic factors as well as the rotational split. PMID- 11759907 TI - Solvent exposures in screen printing shops. AB - A comprehensive description of working conditions, exposure patterns for organic solvents, and related health symptoms among workers in ten small screen printing companies located in Seattle, Washington, is presented. Sampling methods included continuous area monitoring, grab sampling, personal sampling, and time study observation. A total of 27 workers were observed and monitored for solvent exposure. Short-term peak exposures were characterized in terms of magnitude, duration and repetition, and their contribution to time weighted average (TWA) exposures were evaluated. A health questionnaire addressing the symptoms potentially attributable to solvents was used to investigate the possible health effects from exposure. Significant differences in the prevalence of headaches, dizziness, intoxication, and dry skin (p < 0.01) were reported among workers who had some solvent exposure compared with the referent group that was not exposed. Exposed workers were also more likely to report fatigue, loss of strength in the arms and hands, difficulty concentrating, sore throat, and a low alcohol tolerance. The study documented highly variable levels of solvent exposures. Screen printing workers in different companies, while performing the same basic tasks, had time weighted average (TWA) exposures ranging from 2% to 100% of the recommended threshold limit value (TLV) for mixtures. Continuous monitoring indicated that high short-term exposures are responsible for the bulk of TWA exposures. Grab samples and continuous monitoring verified that recommended Short Term Exposure Limits (STEL) for individual solvents may be exceeded on a routine basis. Frequent skin contact with solvents was also observed. Health problems in this industry and other small industries using organic solvents may result from these complex patterns of exposure. PMID- 11759908 TI - Environmental impacts of phosphogypsum vs. borrow pits in roadfill construction. AB - A comparison was performed of the environmental impacts of using phosphogypsum versus conventional fill materials (e.g., from borrow pits) for road construction. The study compared a hypothetical roadway with an actual roadway in Florida; the two facilities differed only in that phosphogypsum was employed as fill material instead of conventional materials. The effect of the two construction approaches on the plant and animal communities was considered, as was the impact on the surface and ground water. A summary was made of the comparative impacts, and a comparison matrix was constructed using integral numbers to depict impacts ranging from -5 (most impact) to 0 (none) to + 5, showing most benefit of the part of the project on a given resource. Values were subjective, based upon investigators' experience. Four categories (plant and animal communities, water quality, water resources, and air quality) were considered. The cumulative total was +12 for phosphogypsum and -6 for conventional fill material. PMID- 11759909 TI - Rheological behavior of Phanerochaete chrysosporium broth during lignin degradation. AB - Rheological behavior of a lignin-degrading culture of Phanerochaete chrysosporium CDBB-H-298 was determined. Rheological characteristics revealed a Newtonian behavior in the culture medium without fungi, and a non-Newtonian dilatant behavior with fungi. In addition, the rheological behavior of the lignin containing culture medium was complex, and changed from dilatant to pseudoplastic. During fungal growth without lignin in Kirk media rheological behavior exhibited a parabolic profile, and thixotropy showed a tendency to increase. Results indicated a small increase in the apparent viscosity in the presence of lignin; however, this may not affect the oxygen and mass transfer coefficients. The present findings can be applied to bioreactor desing for waste water treatment. PMID- 11759910 TI - Electrochemical oxidation of resorcinol for wastewater treatment using Ti/TiO2 RuO2-IrO2 electrode. AB - Electrochemical oxidation of resorcinol for wastewater treatment in the presence of chloride was investigated. Titanium Substrate Insoluble Anode (TSIA) coated with TiO2-RuO2-IrO2 was used as an anode and graphite carbon sheet was used as a cathode. The extent of resorcinol electrochemical oxidation was determined in terms of COD removal. The Box-Behnken second order composite design was used to study the effect of operating parameters such as initial pH, chloride concentration, initial concentration of resorcinol and charge input. The experimental values were in good correlation with predicted values, and the correlation coefficient was found to be good. The effect of current density on resorcinol oxidation, the AOX level during the electrochemical treatment and TOC removal were also studied for selected conditions. It has been observed that the extended electrolysis brings down the AOX concentration to lower levels. The maximum current efficiency was observed at higher resorcinol concentration, higher chloride concentration and increasing current density. PMID- 11759911 TI - Treatment of phosphoric acid plant wastewater using Fenton's reagent and coagulants. AB - The results of treatability studies viz., Fenton reaction and physico-chemical (coagulation) treatment using lime, alum, Fe salts and polyaluminium chloride (PAC) performed on wastewater generated from a unit manufacturing technical grade phosphoric acid are reported. Due to low biochemical oxygen demand (BOD) chemical oxygen demand (COD) ratio and very low pH, this wastewater is not amenable for biological treatment. The treatability studies indicated that it is possible to remove 75-80% COD using Fenton's reagent at optimum doses of 1.0 g/L FeSO4 and 2 ml of 30% H2O2. Simultaneously, significant quantities of suspended solids, phosphate and fluoride are also removed. Polyaluminium chloride is found to be more effective towards suspended solids (SS), COD, phosphate and fluoride removal, when compared to other coagulants used in the present study. Addition of an anionic polyelectrolyte (Magnafloc 156) to PAC improved the performance further. A treatment scheme that consists of neutralization (pH 4) + Fenton's reagent + neutralization (pH 7.5) + PAC/Magnafloc 156 is found to be effective in treating phosphoric acid plant wastewater to meet marine discharge standards. PMID- 11759912 TI - Effect of a hydrolytic/acidogenic pre-stage on the organic matter content of wastewater treated in a sequencing batch reactor for biological phosphorous removal. AB - An increase of 52.7% in acetate concentration was observed when urban wastewater was used to feed a pilot-scale upflow-type, fixed-bed fermentor under a hydraulic retention time of 0.78 h. The fermentor influent and effluent were successively used to feed a laboratory-scale sequencing batch reactor (SBR) using similar operational variables of wastewater volume, sludge purging volume and retention times during the anaerobic and aerobic phase, giving a nominal 4 h hydraulic retention time. The fermentor effluent contained an organic substrate, with a volatile fatty acid content higher than 50mg L(-1), which was appropriate for the growth of the type of microorganisms characteristically found in biological phosphorous removal (BPR) systems, and showed the behaviour of an easily and rapidly biodegradable wastewater. The specific rate of phosphorous release at the anaerobic stage was found to be higher than 0.04mg Pr g VSS(-1) min(-1), when the fermentor effluent is used as feed of the SBR, which demonstrated its favourable conditions for an efficient processing in this type of systems. PMID- 11759913 TI - Uptake and distribution of mercury in rats after repeated administration of mercuric chloride. AB - This investigation was under taken to evaluate the effect of repeated exposure of mercuric chloride (MC) on food consumption, body weight gain and tissue distribution of mercury in rats. After two weeks of acclimation, male and female rats (45-50 days old) were orally gavaged with 0.00, 2.0, 4.0 6.0, 8.0 or 10.0 mg/kg/day of MC for 14 consecutive days. The mortality and food consumption were recorded daily. The body weight gains were recorded on day 0, 4, 7, 10, and at day of termination. At the end of the experiment, all surviving rats were euthanized and tissue samples from their brains, gonads, hearts, kidneys, livers, lungs, pancreases and spleens were collected and analyzed for mercury content. Exposure of male and female rats to 4.0 mg/kg/day of MC showed a significant reduction in body weight gain and food consumption when compared to their controls. However, at 2.0 mg/kg/day dose group showed no change of body gain and food consumption. The mercury contents in brains, gonads, hearts, and spleens of male and female rats at 0.0 and 2.0 mg/kg/day were undetectable. Both male and female rats accumulated significantly more mercury in the kidneys than the other organs. Mercury content in the kidneys of females was 39.9 and 40.9 microg/g at 2.0 and 4.0 mg/kg/day, respectively and of males was 34.9 and 41.0 microg/g at 2.0 and 4.0 mg/kg/day, respectively. However, mercury content in the kidneys and livers of males and females did not show any significant difference. Mercury content in the kidneys of both of sexes was significantly higher than the other organs. PMID- 11759914 TI - Mercury adsorption onto pyrolyzed waste paper. AB - The ability of pyrolyzed waste paper to remove mercury from aqueous solutions by physicochemical adsorption was investigated. Defibered waste newsprint was pyrolyzed in a nitrogen atmosphere at 300 degrees C for 3 h. The pyrolysis residue showed high affinity to inorganic divalent mercury species. To investigate the adsorption characteristics, the factors affecting mercury adsorption were examined. The adsorbent was efficient in capturing mercury in neutral and basic media, although limited adsorption occurred in acidic media. The extent of the adsorption was also dependent upon the solution temperature and initial concentration of mercury in solution. The adsorption followed both the Langmuir and Freundlich isotherms. PMID- 11759915 TI - Wet air oxidation of a direct dye solution catalyzed by CoAlPO4 -5. Performance assessment and kinetic study. AB - Wet air oxidation (WAO) of a prepared direct dye solution was tested by using the CoAIPO4 -5 catalyst. Addition of CoAIPO4 -5 could effectively improve rate of color removal and the activation energy of color removal could decrease from about 110 kJ/mole to about 75 kJ/mole as the catalyst loading was increased from 0.0 g/L to 3.0 g/L. Performance of WAO on color removal would somewhat increase with catalyst loading at 145 degrees C whereas the effect of catalyst loading was not significant at 135 degrees C. With no addition of CoAlPO4 -5, the chemical oxygen demand (COD) value was low. This was due to difficulty of exactly measuring the true COD value of dye solution if the dye was not degraded. Via CoAIPO4 -5, COD of dye solution could be effectively decreased. The rate of COD removal would increase with catalyst loading, oxygen pressure and reaction temperature. Furthermore, a maximum COD value observed, which was due to catalyzed degradation of dye molecule via CoAlPO4 -5, could be characterized by a consecutive reaction scheme. Kinetic study of color removal is expressed as follows: rate = k x [dye](0.8) x W(0.5) x P(n) (145 degrees C) or rate = k x [dye](0.8) x W(0) x P(n) (135 degrees C); where k means rate constant, [] means concentration, W means catalyst loading, P means oxygen pressure and n means uncertain number. PMID- 11759916 TI - Synergic degradation of reactive brilliant red X-3B using three dimension electrode-photocatalytic reactor. AB - A new reactor, three dimension electrode-photocatalytic reactor, was designed and used to investigate the photoelectrochemical degradation of reactive brilliant red X-3B (RBRX) in simulated wastewater. The reactor was characterized by a series of parameters, the current change, decolorization ratio, COD removal and degradation ratio. It was found that the three dimensional electrode photocatalytic reactor could effectively destroy the RBRX within a reaction time of 30 min. The results also showed that the photoelectrochemical process is more efficient than the single application of electrochemical oxidation or photocatalytic degradation. The degradation reactions of RBRX conformed to pseudo first order kinetics in the three processes, and an apparent synergic effect in the increase of the photocurrent and the disappearance of RBRX was observed by combining the electrochemistry with photocatalytic process in the three dimension electrode-photocatalytic reactor. PMID- 11759918 TI - The importance of anisotropy in modeling ST segment shift in subendocardial ischaemia. AB - In this paper, a simple mathematical model of a slab of cardiac tissue is presented in an attempt to better understand the relationship between subendocardial ischaemia and the resulting epicardial potential distributions. The cardiac tissue is represented by the bidomain model where tissue anisotropy and fiber rotation have been incorporated with a view to predicting the epicardial surface potential distribution. The source of electric potential in this steady-state problem is the difference between plateau potentials in normal and ischaemic tissue, where it is assumed that ischaemic tissue has a lower plateau potential. Simulations with tissue anisotropy and no fiber rotation are also considered. Simulations are performed for various thicknesses of the transition region between normal and ischaemic tissue and for various sizes of the ischaemic region. The simulated epicardial potential distributions, based on an anisotropic model of the cardiac tissue, show that there are large potential gradients above the border of the ischaemic region and that there are dips in the potential distribution above the region of ischaemia. It could be concluded from the simulations that it would be possible to predict the region of subendocardial ischaemia from the epicardial potential distribution, a conclusion contrary to observed experimental data. Possible reasons for this discrepancy are discussed. In the interests of mathematical simplicity, isotropic models of the cardiac tissue are also considered, but results from these simulations predict epicardial potential distributions vastly different from experimental observations. A major conclusion from this work is that tissue anisotropy and fiber rotation must be included to obtain meaningful and realistic epicardial potential distributions. PMID- 11759917 TI - A model of the muscle action potential for describing the leading edge, terminal wave, and slow afterwave. AB - The leading edge, terminal wave, and slow afterwave of the motor-unit action potential (MUAP) are produced by changes in the strength of electrical sources in the muscle fibers rather than by movement of sources. The latencies and shapes of these features are, therefore, determined primarily by the motor-unit (MU) architecture and the intracellular action potential (IAP), rather than by the volume-conduction characteristics of the limb. We present a simple model to explain these relationships. The MUAP is modeled as the convolution of a source function related to the IAP and a weighting function related to the MU architecture. The IAP waveform is modeled as the sum of a spike and a slow repolarization phase. The MU architecture is modeled by assuming that the individual fibers lie along a single equivalent axis but that their action potentials have dispersed initiation and termination times. The model is illustrated by simulating experimentally recorded MUAPs and compound muscle action potentials. PMID- 11759919 TI - An investigation of the importance of myocardial anisotropy in finite-element modeling of the heart: methodology and application to the estimation of defibrillation efficacy. AB - Finite-element (FE) modeling has been widely used in studies of bioelectric phenomena of tissues, including ventricular defibrillation. Most FE models, whether built from anatomical atlases or subject-specific tomographic images, treat the myocardium as an isotropic tissue. However, myocardium has been experimentally shown to have significant anisotropy in its resistivities, although myocardial fiber directions are difficult to measure on a subject specific basis. In this paper, we: 1). propose a method to incorporate a widely known myocardial fiber direction model to a specific individual and 2). assess the effects of myocardial anisotropy on myocardial voltage gradients computed for a study of implantable defibrillators. The thoracic FE model was built from CT images of a young pig, and the myocardial fiber structures were incorporated via elastic mapping. Our results demonstrate a good mapping of geometry between the source and target hearts with an average root-mean-square error of less than 2.3 mm and a mapped fiber pattern similar to those known to exist in vivo. With the mapped fiber information, we showed that the estimated minimal myocardial voltage gradient over 80% of the myocardium differs by less than 10% between using an isotropic and anisotropic myocardial models. Thus, myocardial anisotropy is expected to have only a small effect on estimates of defibrillation threshold obtained from computed voltage gradients. On the other hand, anisotropy may be essential if defibrillation efficacy is analyzed by transmembrane voltage of the myocardial cells. PMID- 11759920 TI - A finite-element study of the effects of electrode position on the measured impedance change in impedance cardiography. AB - Traditional impedance cardiography (ICG) technique uses band electrodes both for delivering current to and measuring impedance change in the thorax. The use of spot electrodes increases the ease of electrode placement and comfort level for patients. Research has shown that changes in thoracic impedance can have multiple causes. In this study, we used finite element modeling to investigate the sources of impedance change for both band-electrode and spot-electrode ICG, and focused on how differences in electrode location affect the contribution of different sources to changes in impedance. The ultimate purpose is to identify the optimal electrode type and placement for the sensing of stroke volume (SV). Our models were built on sets of end-diastolic and end-systolic magnetic resonance images of a healthy human subject. The results showed that the effect of ventricular contraction is opposite to that of the other changes in systole: the expansion of major vessels, decrease in blood resistivity due to increased blood flow velocity, and decrease in lung resistivity due to increased blood perfusion. Ventricular contraction, the only factor that tends to increase systolic impedance, has a larger effect than any of the other factors. When spot electrodes are placed on the anterior chest wall near the heart, ventricular contraction is so dominant that the measured impedance increases from end diastole to end-systole, and the change represents 82% of the contribution from ventricular contraction. When using the common band-electrode configuration, the change in measured impedance is a more balanced combination of the four effects, and ventricular contraction is overcome by the other three factors so that the impedance decreases. These results suggest that the belief that ICG can be used to directly measure SV based on the change in the whole thoracic impedance may be invalid, and that spot electrodes may be more useful for understanding local physiological events such as ventricular volume change. These findings are supported by previously reported experimental observations. PMID- 11759921 TI - Model-based analysis of dynamics in vergence adaptation. AB - We previously proposed a model to study the dynamics of disparity vergence responses. This model was based on known physiology and consisted of pulse and step neural control processes feeding a linear second-order oculomotor plant. Here, we apply a slightly modified version of that model to analyze the influence of short-term adaptation on vergence dynamics. This analysis showed that, unlike normal vergence responses, adapted responses could not be accurately simulated without a delay between the step and pulse components. Through simulations of normal vergence and adapted vergence responses, we found a strong correlation between delay of the step signal and the size of the movement overshoot. This correlation suggests a strong interaction between neural process generating the pulse and step motor control signals. PMID- 11759922 TI - Computer-assisted sleep staging. AB - To address the subjectivity in manual scoring of polysomnograms, a computer assisted sleep staging method is presented in this paper. The method uses the principles of segmentation and self-organization (clustering) based on primitive sleep-related features to find the pseudonatural stages present in the record. Sample epochs of these natural stages are presented to the user, who can classify them according to the Rechtschaffen and Kales (RK) or any other standard. The method then learns from these samples to complete the classification. This step allows the active participation of the operator in order to customize the staging to his/her preferences. The method was developed and tested using 12 records of varying types (normal, abnormal, male, female, varying age groups). Results showed an overall concurrence of 80.6% with manual scoring of 20-s epochs according to RK standard. The greatest amount of errors occurred in the identification of the highly transitional Stage 1, 54% of which was misclassified into neighboring stages 2 or Wake. PMID- 11759924 TI - A fast method to derive realistic BEM models for E/MEG source reconstruction. AB - A fast method for segmentation of a subject's skin, skull or brain compartment for electroencephalogram (EEG)/magnetoencephalogram (MEG) (E/MEG) source localization is proposed. The method is based on a description of volumes with spherical harmonics and a database of exact surfaces. Using the spherical harmonic coefficients, sets of basis surfaces are obtained for each compartment. New segmentations can be acquired by combining the appropriate basis surfaces to describe a delineation of the volume in a limited number of magnetic resonance (MR) slices. Alternatively, a representation of the skin can be derived from digitized head shape. Skull and brain then can be predicted from the skin representation with a prediction model also obtained from the segmentation database. Database segmentations were recomputed with the proposed method. Mean deviations from the originals were about 2 and 3 mm for compartments derived from MR and head shape. Dipole simulations with original surfaces for forward and computed segmentations for inverse calculations showed average dipole mislocalizations of 1.6 and 3.3 mm, respectively. With the proposed method highly accurate segmentation can be performed with much less effort and in much less time compared with other techniques. The method also is applicable when MR data is unavailable but a digitization of the head is. PMID- 11759923 TI - EEG complexity as a measure of depth of anesthesia for patients. AB - A new approach for quantifying the relationship between brain activity patterns and depth of anesthesia (DOA) is presented by analyzing the spatio-temporal patterns in the electroencephalogram (EEG) using Lempel-Ziv complexity analysis. Twenty-seven patients undergoing vascular surgery were studied under general anesthesia with sevoflurane, isoflurane, propofol, or desflurane. The EEG was recorded continuously during the procedure and patients' anesthesia states were assessed according to the responsiveness component of the observer's assessment of alertness/sedation (OAA/S) score. An OAA/S score of zero or one was considered asleep and two or greater was considered awake. Complexity of the EEG was quantitatively estimated by the measure C(n), whose performance in discriminating awake and asleep states was analyzed by statistics for different anesthetic techniques and different patient populations. Compared with other measures, such as approximate entropy, spectral entropy, and median frequency, C(n) not only demonstrates better performance (93% accuracy) across all of the patients, but also is an easier algorithm to implement for real-time use. The study shows that C(n) is a very useful and promising EEG-derived parameter for characterizing the (DOA) under clinical situations. PMID- 11759925 TI - Locating a catheter transducer in a three-dimensional ultrasound imaging field. AB - Cardiac procedures rely on fluoroscopy for catheter guidance and visualization. However, fluoroscopy provides poor contrast of myocardial structures and exposes both the patient and health care providers to ionizing radiation. As an alternative to fluoroscopy, real-time three-dimensional (3-D) ultrasound imaging has the potential to provide a safe means for tracking catheter position in 3-D while simultaneously imaging the heart's anatomy. A method is described for locating a catheter-mounted transducer in the 3-D ultrasound imaging field. The distance from the imaging transducer to the catheter transducer is measured by time of flight, while the angular position is determined by a spatial crosscorrelation of the received signals with stored receive profiles. Results from simulations with 20-dB SNR demonstrated a mean accuracy of 0.22 +/- 0.13 mm at a 70-mm range. In vitro testing showed a resolution of 0.23 +/- 0.11 mm at a range of 75 mm and a resolution of 0.47 +/- 0.47 mm at a range of 97 mm. With combined catheter position and imaging, this tracking method has the potential to replace fluoroscopy and enhance interventional procedures. PMID- 11759926 TI - Noninvasive vasectomy using a focused ultrasound clip: thermal measurements and simulations. AB - INTRODUCTION: Conventional surgical vasectomy may lead to complications including bleeding, infection, and scrotal pain. Noninvasive transcutaneous delivery of therapeutic focused ultrasound has previously been shown to thermally occlude the vas deferens. However, skin burns and inconsistent vas occlusion have presented complications. This study uses bio-heat transfer simulations and thermocouple measurements to determine the optimal ablation dosimetry for vas occlusion without skin burns. METHODS: A 2-rad ultrasound transducer mounted on a vasectomy clip-delivered ultrasound energy at 4 MHz to the canine vas deferens co-located at the focus between the clip jaws. Chilled degassed water was circulated through an attached latex balloon, providing efficient ultrasound coupling into the tissue and active skin cooling to prevent skin burns. Thermocouples placed at the vas, intradermal, and skin surface locations recorded temperatures during ablation. Procedures were performed with transducer acoustic powers of 3-7 W and sonication times of 60-120 s on both the left and right vas deferens (n = 2) in a total of four dogs (precooling control, 3 W/120 s, 5 W/90 s, 7 W/60 s). Measurements were compared with bio-heat transfer simulations modeling the effects of variations in power and sonication time on tissue temperatures and coagulation zones. RESULTS: Active skin cooling produces a thermal gradient in the tissue during ablation, allowing sufficient thermal doses to be delivered to the vas without skin burns. However, low-power, long-duration heating produced excessive tissue necrosis due to thermal diffusion, while high power and short heating times reduced the therapeutic window and produced skin burns presumably due to direct ultrasound absorption. CONCLUSIONS: Both simulations and experiments suggest that a therapeutic window exists in which thermal occlusion of the vas may be achieved without the formation of skin burns in the canine model (power = 5-7 W, surface intensity = 1.4-1.9 W/cm2, time = 20-50 s). This range of ablation parameters will help guide future experiments to refine incisionless vasectomy using focused ultrasound. PMID- 11759927 TI - A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells. AB - We present a novel approach to implementing the dynamic-clamp protocol (Sharp et al., 1993), commonly used in neurophysiology and cardiac electrophysiology experiments. Our approach is based on real-time extensions to the Linux operating system. Conventional PC-based approaches have typically utilized single-cycle computational rates of 10 kHz or slower. In thispaper, we demonstrate reliable cycle-to-cycle rates as fast as 50 kHz. Our system, which we call model reference current injection (MRCI); pronounced merci is also capable of episodic logging of internal state variables and interactive manipulation of model parameters. The limiting factor in achieving high speeds was not processor speed or model complexity, but cycle jitter inherent in the CPU/motherboard performance. We demonstrate these high speeds and flexibility with two examples: 1) adding action potential ionic currents to a mammalian neuron under whole-cell patch-clamp and 2) altering a cell's intrinsic dynamics via MRCI while simultaneously coupling it via artificial synapses to an internal computational model cell. These higher rates greatly extend the applicability of this technique to the study of fast electrophysiological currents such fast a currents and fast excitatory/inhibitory synapses. PMID- 11759928 TI - An integrated circuit implementation of the Huxley sarcomere model. AB - We have developed an integrated circuit to simulate the mechanical behavior demonstrated by sarcomeres found in skeletal muscle. The circuit is based upon the mathematical description of the attachment and detachment dynamics of crossbridge populations and the force generated by the crossbridges, originally formulated by A. F. Huxley. We describe the process of designing the circuit model from the mathematical model, present the sarcomere circuit implementation, and demonstrate the transient and steady-state behaviors that the fabricated circuit produces. Comparison of our results to published mechanical behavior of skeletal muscle shows qualitative similarities. We conclude that the circuit muscle model exhibits the potential for real-time simulation of muscle contractions and could be used to give engineered systems muscle-like properties. PMID- 11759929 TI - A model of the muscle-fiber intracellular action potential waveform, including the slow repolarization phase. AB - Recent studies have shown that the slow repolarization phase or "negative afterpotential" of the intracellular muscle-fiber action potential (IAP) plays an important role in determining the shape of the extracellularly recorded motor unit action potential (MUAP). This paper presents a model of the IAP waveform as the sum of a spike and an afterpotential, both represented by simple analytical expressions. The model parameters that specify the sizes of the spike and afterpotential are shown to be proportional to the quadrupole and dipole moments of the transmembrane current distribution associated with the spike of the wave of excitation. The model provides a computationally efficient method for simulating the MUAP, and it can be reliably inverted to estimate the model parameters from empirical IAP and MUAP waveforms. PMID- 11759930 TI - Coherence-weighted Wiener filtering of somatosensory evoked potentials. AB - In this paper, we present a Wiener filtering (WF) approach for extraction of somatosensory evoked potentials (SEPs) from the background electroencephalogram (EEG), with sweep-to-sweep variations in its signal power. To account for the EEG power variations, WF is modified by iteratively weighting the power spectrum using the coherence function. Coherence-weighted Wiener filtering (CWWF) is able to extract SEP waveforms, which have a greater level of detail as compared with conventional time-domain averaging (TDA). Using CWWF, the components of the SEP show significantly less variability. As such, CWWF should be useful as an important diagnostic tool able to detect minimal changes in the SEP. In an experimental study of cerebral hypoxia, CWWF is shown to be more responsive to detection of injury than WF or TDA. PMID- 11759931 TI - Coping with syncope: tilt towards pacing. PMID- 11759932 TI - New techniques for mapping cardiac arrhythmias. PMID- 11759933 TI - Carotid artery stenting: current status and future prospects. PMID- 11759934 TI - Role of thrombolytic therapy for stuck prosthetic valves: a serial echocardiographic study. AB - BACKGROUND: Thrombotic occlusion of a prosthetic valve continues to be an uncommon but serious complication. Intravenous thrombolytic therapy has been proposed as an alternative to surgical treatment, but only in critically ill patients. METHODS AND RESULTS: Forty-one consecutive patients presenting with 48 episodes of prosthetic valve thrombosis (44 mitral and 4 aortic) were treated with thrombolytic therapy under serial echocardiographic guidance. There were 14 male and 27 female patients. The anticoagulation status was inadequate in 89.6% of episodes. Atrial fibrillation was present in 47.9% of episodes. The prostheses involved in these episodes were tilting disc in 45, bileaflet in 2, and ball and cage type in 1. The Sorin prosthetic valve was the most commonly involved. The time interval between valve replacement and thrombosis ranged from 1 month to 108 months (mean 20.4+/-20.6 months). Patients were in New York Heart Association functional class III in 47.9% and in class II in 43.9% of episodes. Thrombolytic agents used were streptokinase and urokinase in 44 and 4 episodes, respectively. The mean duration of thrombolytic therapy was 27.9+/-15.0 hours and the overall success rate was 87.5%. Patients developed peripheral embolism with almost complete recovery in 5 episodes while significant bleeding that required termination of thrombolytic therapy was observed in 2 episodes. Redo valve replacement was done in 3 episodes because these patients did not improve on thrombolytic therapy (all 3 cases were of recurrent prosthetic valve thrombosis and were found to have pannus peroperatively). Three patients died during thrombolytic therapy because of persistent heart failure. Six patients experienced a total of 13 epidoses of recurrent prosthetic valve thrombosis including index episodes (rethrombosis in 5, re-rethrombosis in 1). They were treated with repeated thrombolysis with a success rate of 76.92%. The mean duration of thrombolytic therapy in these episodes was 36.1+/-14.0 hours. CONCLUSIONS: In patients with prosthetic valve thrombosis, intravenous thrombolysis guided by echocardiography is a safe and effective method that may expand the indications for nonsurgical treatment of prosthetic valve thrombosis. By using serial echocardiography, the duration of thrombolytic therapy can be tailored to the patient's requirement for normalization of valve hemodynamics. PMID- 11759935 TI - Carotid intima-media thickness as an independent predictor of coronary artery disease. AB - BACKGROUND: A noninvasive technique of measuring carotid artery intima-media thickness has recently generated considerable interest as a marker of atherosclerosis and in the prediction of clinical coronary events and coronary artery disease. The present study evaluated the association of carotid artery intima-media thickness in the prediction of coronary artery disease in a western Indian population. METHODS AND RESULTS: Carotid artery intima-media thickness was measured with a B-mode scan in an ongoing study of 266 patients, who were further subdivided into 4 subgroups: those with non-insulin dependent diabetes mellitus; hypertension; diabetes mellitus with hypertension; and those without diabetes or hypertension (labeled as controls). The maximal intima-media thickness greater than 0.8 mm at the far wall of the common carotid artery, excluding raised lesions and plaques, was selected as the highest value for comparison. The subgroups were further divided into those with and without apparent coronary artery disease. A statistically significant intima-media thickness greater than 0.8 mm was observed in 59.2% of the subjects with coronary artery disease as against 40.8% in those without the disease on univariate analysis. A higher incidence of intima-media thickness of more than 0.8 mm was observed in all subgroups with coronary artery disease as against those without the disease, which was most marked in the hypertensive group (22.2% v. 3.6%) and contributed to the increased arterial thickness in diabetics with concomitant hypertension. Multivariate regression analysis revealed carotid artery intima-media thickness to be associated with coronary artery disease with an odds ratio of 2.40. CONCLUSIONS: Carotid artery intima-media thickness is a simple, noninvasive and reproducible clinical tool to evaluate atherosclerosis and predict coronary artery disease in Indian subjects. Prospective studies in a larger number of subjects, particularly in those undergoing coronary angiography, will help in establishing the role of this technique. PMID- 11759936 TI - Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives. AB - BACKGROUND: Studies among emigrant Indians have stressed the role of a powerful genetic factor, lipoprotein (a), in the causation of premature coronary artery disease. This study was carried out to assess lipoprotein (a) and lipid levels in 50 consecutive young north Indian patients (age less than 45 years, mean age 39+/ 3.7 years) with myocardial infarction, their first-degree relatives (n=125, mean age 36+/-16 years), and age- and sex-matched controls (n=50, mean age 34+/-6.9 years). METHODS AND RESULTS: Blood samples for lipid estimation were taken within 24 hours of myocardial infarction and after overnight fasting for twelve hours. Lipoprotein (a) levels were estimated by the ELISA technique using preformed antibodies while lipid levels were estimated by kits using the colorimetric method. All were male patients. The mean lipoprotein (a) level was 22.28+5.4 mg/dl in patients, 13.88+5.19 mg/dl in their first-degree relatives and 9.28+22.59 mg/dl in controls. In addition, it was significantly higher in young patients with myocardial infarction and their relatives as compared to controls (p<0.001 for patients v. controls and p<0.05 for relatives v. controls). There was no significant difference in the levels of total cholesterol and low-density lipoprotein cholesterol among the three groups. High-density lipoprotein cholesterol was significantly lower in young patients with myocardial infarction (30.16+/-9.45 mg/dl) and their first-degree relatives (33.28+/-8.45 mg/dl) as compared to controls (46.8+/-8.04 mg/dl) (p<0.001 for patients v. controls and p<0.01 for relatives v. controls). Triglyceride levels were significantly higher in patients as compared to controls (202+/-76 mg/dl v. 149 + 82.99 mg/dl, p<0.05). Smoking was more prevalent in young patients with myocardial infarction as compared to controls (44% v. 36%, p<0.05). CONCLUSIONS: Smoking, high lipoprotein (a) and triglyceride levels and low high-density lipoprotein levels may be important risk factors for coronary artery disease in the younger population; also, there is familial clustering of high lipoprotein (a) levels in first-degree relatives of young patients with myocardial infarction. PMID- 11759938 TI - Long-term performance of single-pass physiological pacing. AB - BACKGROUND: Single-pass physiological pacing has several advantages over dual lead physiological pacing. The present study evaluated the long-term performance of single-pass pacing using the overlapping biphasic impulse stimulation technique. METHODS AND RESULTS: A total of 30 patients with single-pass VDD pacing and 8 patients with single-pass DDDC pacing were followed up for 1 year by basal and magnet electrocardiograms and real-time telemetry. All the patients showed satisfactory atrial sensing and pacing capture threshold. The atrial sensing thresholds at implant and at 1 month, 3 months, 6 months and 12 months of follow-up were 2.5+/-0.67 mV, 1.6+/-0.6 mV, 1.1+/-0.5 mV, 1.0+/-0.5 mV and 1.0+/ 0.04 mV, respectively. The corresponding values for atrial pacing threshold at a pulse wave of 0.5 ms were 2.5+/-1.0 V, 4.4+/-0.9 V, 3.8+/-1.2 V, 3.6+/-1.4 V and 3.8+/-1.4 V. Of the patients with DDDC pacing, 88% showed stable pacing capture in the supine position, 75% in the upright position and 62% in both positions. Diaphragmatic contraction was seen in 25% of cases with DDDC pacing. No such event was seen in patients with VDD pacing. CONCLUSIONS: Single-pass pacing is safe, technically easy and cheap as compared to dual-lead systems. However, it would be prudent to recommend DDDC pacing in patients who require predominantly VDD pacing and only occasionally atrial pacing, as the latter showed a low percentage of stable atrial pacing capture in both upright and supine positions as well as a significant percentage of diaphragmatic contraction. PMID- 11759937 TI - A cardiac evoked response algorithm providing automatic threshold tracking for continuous capture verification: a single-center prospective study. AB - BACKGROUND: The AutoCapture algorithm as implemented in Regency and Microny pacemakers (Pacesetter Inc., Sylmar, CA, USA) provides beat-by-beat monitoring of capture based on proper detection of the evoked response, provides high output back-up pulse when loss of capture occurs, performs periodic threshold evaluations and acquires the capture threshold data in a time-based event counter for later retrieval. The safety and efficacy of this algorithm was prospectively evaluated at a tertiary care hospital of north India. METHODS AND RESULTS: Fifty four patients (38 males, mean age 66+/-13 years) received a ventricular pacemaker model Regency SC+ with low polarization bipolar lead for high-grade atrioventricular block (n=42) and sick sinus syndrome (n=12). Evoked response and polarization signal were assessed initially at 24 hours postimplant, and follow up measurements were systematically conducted at week 1 and months 1, 3 and 6. Further evaluation of eligible patients was performed at 6-monthly intervals. Lead implantation parameters were optimum in all patients. At 6 months, the algorithm was functional in 51 patients. The pacing threshold increased to 0.89+/ 0.36 V (p<0.001) in the first month and stabilized thereafter. Significant saving of energy was accomplished by a constant output safety margin of 0.3 V instead of the traditional 100%. While the evoked response signal remained stable throughout the study period, the potential signal increased significantly from 0.6+/-0.7 mV to 1.0+/-0.6 mV (p<0.001) in the first month and remained steady subsequently. Back-up pacing in the event of exit block was confirmed in all 25 patients who underwent a 24-hour Holter test. Based on the suggested sense margins, ventricular undersensing was observed in 7 (28%) patients, the majority of whom had competitive cardiac rhythms. An elderly patient with pneumonic illness succumbed to pulmonary embolism at 6 months. CONCLUSIONS: This large single center experience on AutoCapture demonstrates the success of this algorithm in low-energy ventricular pacing without compromising the patient's safety. PMID- 11759939 TI - Pheochromocytoma: a 10-year experience in a tertiary care North Indian hospital. AB - BACKGROUND: The study was carried out to highlight the clinical and biochemical profile of patients with pheochromocytoma in a tertiary care center of North India. METHODS AND RESULTS: Thirty consecutive cases of pheochromocytoma admitted over a period of 10 years to our Institute were analyzed. The chief clinical complaints of these 30 patients (17 males and 13 females, mean age 24+/-7 years) were palpitation (80%), headache (77%), sweating (60%), breathlessness (67%) and flushing (56%). The clinical triad of headache, flushing and sweating occurred in 26.7% of cases. On clinical examination, 97% of the patients were hypertensive and 16.6% presented with malignant hypertension. Laboratory measurements showed that the levels of 24-hour urinary vanillylmandelic acid were elevated in 80% of cases. Levels of plasma adrenaline and noradrenaline were raised in 78% and 79% of cases, respectively. Anatomical localization of the tumor on computerized tomographic scan showed the presence of an adrenal tumor in 80% and extra-adrenal tumor in 20%. Surgical removal of the tumor could be carried out in 28 cases following control of the blood pressure with antihypertensive drugs including alpha and beta adrenoreceptor blockers. CONCLUSIONS: Pheochromocytoma should be suspected in all young hypertensive persons. The appropriate therapy for this tumor is surgical removal preceded by adequate blood pressure control including the use of alpha and beta adrenoreceptor antagonists. PMID- 11759940 TI - Endomyocardial fibrosis is associated with selective deposition of type I collagen. AB - BACKGROUND: Endomyocardial fibrosis is a distinct form of heart disease leading to restrictive ventricular filling and cardiac failure. The disease is characterized by a marked thickening of the endocardium due to the deposition of dense fibrous tissue composed of wavy bundles of collagen. Changes in collagen composition and an abnormal increase in its concentration result in a stiffer myocardium and ventricular diastolic dysfunction. The nature of cardiac collagens and the relative proportions of collagen types in endomyocardial fibrosis have not been documented in the literature. METHODS AND RESULTS: This study analyzed collagen composition in the cardiac tissues of 13 patients with endomyocardial fibrosis and 6 individuals who were the victims of traffic accidents or suicidal deaths and did not have any heart disease. We estimated the relative proportions of types I and III collagen after pepsin digestion of the tissue and separation of the emerging peptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The mean type I:III collagen ratio was 0.51+/-0.06 in normal individuals, and 0.93+/-0.43 in patients with endomyocardial fibrosis (p<0.05). The alteration in the type I:III collagen ratio was due to a disproportionate increase in type I collagen. CONCLUSIONS: The results indicate that a selective increase in type I collagen may contribute to the impaired diastolic distension of the ventricles in patients with endomyocardial fibrosis. PMID- 11759941 TI - Percutaneous transluminal angioplasty with cutting balloon and stenting for isolated bilateral aorto-coronary ostial stenosis in a young female. AB - Coronary artery disease involving both coronary ostia (left main and right coronary) is extremely rare in a premenopausal female, without pre-existing coronary risk factors. We report a case of tight bilateral coronary ostial disease which presented in unusual clinical circumstances in a young female, which was successfully revascularized by single-stage aorto-ostial cutting balloon angioplasty and stenting. PMID- 11759942 TI - Transcatheter closure of a large coronary artery fistula with Amplatzer duct occluder: a new approach. AB - We report a new retrograde approach for the successful closure of a large right coronary artery fistula in a 27-year-old man using the Amplatzer duct occluder. The device was deployed through a coronary angioplasty-guiding catheter that had been advanced through the aorta and the dilated right coronary artery into the fistula. This method simplified the procedure by eliminating the need for making a femoral artery-to-femoral vein wire loop. PMID- 11759943 TI - Pre-excitation with syncope: a false lead? AB - An 18-year-old girl with pre-excitation presented with a history of recurrent syncope preceded by palpitation. The accessory pathway, which had a relatively long antegrade effective refractory period of 340 ms, was mapped and successfully ablated in the left lateral region. However, after ablation, she had reproducible sustained polymorphic ventricular tachycardia, which was found to be the cause of her syncope. Thus, alternate mechanisms of tachycardia need to be considered in patients with pre-excitation when the presentation is atypical. PMID- 11759944 TI - Aneurysm of the vein of galen in neonates: report of four cases. AB - In neonates, aneurysm of the vein of Galen often masquerades as cyanotic congenital heart disease. We report 4 cases of neonates presenting with malformation of the vein of Galen at our insititution. An increased awareness of this entity seems warranted. PMID- 11759945 TI - Congenitally unguarded tricuspid valve orifice with a giant right atrium and a massive clot in an asymptomatic adult. AB - Congenitally unguarded tricuspid valve orifice, a variant of tricuspid valve dysplasia, is a rare malformation with protean manifestations. This report describes an asymptomatic adult who, on echocardiographic examination ordered in view of an abnormal 12-lead surface electrocardiogram and plain chest X-ray, was found to have an unguarded tricuspid valve orifice with a giant right atrium (12 x 10 cm), intense spontaneous echo contrast and a large right atrial clot. PMID- 11759946 TI - Isolated cardiac aspergillosis. AB - A 40-year-old man, a known case of Wolff-Parkinson-White syndrome, was admitted to the hospital in an unconscious state. In spite of medical treatment, the patient died within two hours of admission. At autopsy, the deceased was found to have aspergillosis involving the interatrial septum, aortic valve and root of the aorta. The rest of the organs were unremarkable. The patient did not show any obvious signs of being immunocompromised. We report this case of isolated cardiac aspergillosis in an apparently healthy individual. PMID- 11759947 TI - Acute reversible left ventricular dysfunction following general anesthesia. AB - Acute reversible left ventricular dysfunction due to myocardial stunning is a known phenomenon during acute myocardial infarction, coronary angiography, coronary angioplasty or after coronary artery bypass surgery. We report a rare case of acute reversible dysfunction of the myocardium as a complication of general anesthesia in a patient with normal coronary arteries. This is a potentially fatal complication unless recognized early and treated aggressively. PMID- 11759948 TI - Interactions between the renin-angiotensin system and dyslipidemia: relevance in atherogenesis and therapy of coronary heart disease. AB - Hypertension and hypercholesterolemia, two major risk factors for atherosclerotic disease, frequently coexist in patients with hypertension and CAD. Data from clinical studies suggest the existence of lipoprotein-neurohormonal interactions that may adversely affect vascular structure and reactivity. Data from preclinical studies suggest that RAS may be upregulated by abnormal lipids, most likely via production of ox-LDL. On the other hand, activation of RAS leads to release of ROS and transcriptional upregulation of LDL and ox-LDL uptake in macrophages, smooth muscle cells and endothelial cells. These findings extend our understanding of the interplay among risk factors to synergistically increase cardiovascular risk, and of the anti-atherosclerotic effects of local ACE inhibition to reduce cardiovascular risk. Trials aimed at modifying RAS along with drugs lowering total- and LDL-cholesterol levels and inhibitors of oxidative modification of LDL-cholesterol will address the clinical relevance of this biological interaction. PMID- 11759949 TI - Cardiovascular images. Right atrioventricular metastasis of hypernephroma. PMID- 11759950 TI - Egg shell calcification of the aorta in aortoarteritis. PMID- 11759952 TI - Limitation of computerized averaging during stress test. PMID- 11759951 TI - Pacemaker "like" syndrome. PMID- 11759956 TI - Detection limit, cut-off and specificity of an improved rapid assay for cardiac troponin T. AB - The performance of an improved version of the troponin T rapid test TROPT Sensitive was investigated in a multicentre evaluation at twelve centres. The detection limit and the cut-off were determined in a method comparison with Elecsys Troponin T using a total of 365 samples from patients with suspected acute coronary syndromes and 91 samples from healthy blood donors or non cardiological patients. The analytical specificity was determined by measuring 1271 blood samples from blood donors without any myocardial injury. The test cut off (90% of results positive) is 0.08 microg/L, and the detection limit is about 0.05 microg/L. The analytical specificity of the test is between 99.7 and 99.9%. With its small area of undefined significance between positive and negative results and its high sensitivity and specificity, TROPT Sensitive is very well suited to the reliable detection of troponin T positive patients with acute coronary syndromes. PMID- 11759957 TI - Predicting the risk of restenosis after angioplasty in patients with peripheral arterial disease. AB - Restenosis is a serious therapeutic problem after percutaneous transluminal angioplasty (PTA). Strategies for the prevention of late restenosis include the use of antiaggregatory and anticoagulant drugs, aggressive lipid-lowering, intravascular radiation and others. As some of these therapeutic options are not without side effects it is important to identify patients with an increased risk to develop restenosis. Major clinically recognizable risk factors for restenosis are advanced disease stage and female gender. Elevated plasma levels of fibrinogen, Lp(a), CRP, and migration-inducing activity appear to indicate an unfavorable clinical outcome, and so does post-interventional increase of vWF and PAI-1 antigen. For peripheral arterial disease, only one study has addressed the influence of homocysteine levels upon the restenosis rate after PTA. Although homocysteine levels were elevated in >50% of patients at entry, they were not associated with a higher restenosis rate. Currently the available data allow a rough approximation of a patient's individual risk. PMID- 11759958 TI - The correlation of beta-subunit human chorionic gonadotropin level in the serum and first morning urine of patients with gestational trophoblastic disease. AB - The purpose of this cross-sectional study was to determine the correlation of beta subunit human chorionic gonadotropin (beta-hCG) level in the serum and first morning urine samples of patients with gestational trophoblastic disease (GTD). A total of 81 paired serum and first morning urine samples from 24 patients diagnosed with GTD, who had their follow-up at the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University. The paired serum and first morning urine samples were measured for beta-hCG level, using enzyme-linked immunosorbent assay (ELISA). After logarithmic transformation, serum beta-hCG level was strongly and significantly correlated to those of first morning urine samples, with the correlation coefficient of 0.97 (p < 0.01). Among the disease-remission group (serum beta-hCG of less than 5 mIU/ml), the correlation coefficient was 0.52 (p < 0.01), which was still statistically significant. Stronger statistical significance was found in the disease-active group (serum beta-hCG of 5 mIU/ml or higher), with the correlation coefficient of 0.95 (p < 0.01). We concluded that the level of serum beta-hCG was strongly and significantly correlated with those of first morning urine samples, especially in patients with active disease. Determination of beta-hCG level using first morning urine samples can be used as an effective mean in the follow-up of patients with GTD. PMID- 11759959 TI - Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension. AB - OBJECTIVE: Angiotensin Converting Enzyme Inhibitors (ACEIs) have been clearly proven to be effective in blood pressure control and haemodynamic control in heart failure patients. Moreover, there is evidence that ACEIs, both in animal models and in humans, also possess the ability to reduce remodeling in cardiovascular structures. Therefore, the reduction of the occurrence of arterial stiffness, leading to an increase in distensibility, is also anticipated. METHOD: Other than physically measuring arterial wall, the assessment of Pulse Wave Velocity (PWV) is also a widely used index of arterial distensibility, which deteriorates through the course of remodeling. To determine the efficacy of a particular ACEI, perindopril, in increasing arterial distensibility, thus reducing PWV, a 6-month multi-center study was conducted in 146 patients with mild to moderate hypertension. The study population consisted of 70 men and 76 women, aged 56.36 (SD 9.4, range 28-73) years. 73 patients were newly diagnosed, 65 were treated patients but the blood pressure was not controlled, and 8 were treated patients with their blood pressure controlled but with adverse effects in need of switching treatment regimens. RESULTS: Mean blood pressure at the beginning of the study was 164.25/97.49 mmHg and 11.71 m/s (SD 2.29 range 7.35 20.12 m/s) in mean PWV. Perindopril was prescribed tritrating from 4 mg/day to 8 mg/day and adding a diuretic. 106 patients completed the study with 76.4 per cent of patients having their blood pressure controlled (Mean Blood pressure 138.6/85.18 mmHg, SD 11.34 and 7.10 Range 110-170/70-110 mmHg) (p<0.05). Mean PWV reduced to 10.56 m/s (-9.89%) (SD 1.84 range 7.27-15.96 m/s) (p<0.05). CONCLUSION: Anti-hypertensive treatment with perindopril for 6 months was effective in controlling blood pressure and reducing Pulse Wave Velocity reflecting the increase of arterial distensibility. PMID- 11759960 TI - Effect and safety of 17 beta-estradiol vaginal tablet in postmenopausal women with urogenital symptoms. AB - OBJECTIVE: To evaluate the effects of a 17 beta-estradiol vaginal tablet on urogenital symptoms, vaginal pH, vaginal cytology, endometrial thickness, and plasma estradiol level in postmenopausal women with urogenital symptoms. METHOD: Twenty-seven postmenopausal women with urogenital symptoms received 25 microg of a 17 beta-estradiol tablet intravaginally daily for the first 2 weeks, followed by 10 weeks of twice a week dosage. The results of urogenital symptoms, vaginal pH, vaginal cytology, endometrial thickness, and plasma estradiol level were analysed. RESULTS: The urogenital symptoms improved significantly in all women. The mean vaginal pH was significantly decreased. The vaginal cytology showed estrogenic effect on the karyopyknotic index and the maturation value. There was no significant difference in endometrial thickness and level of plasma estradiol before and after treatment. There was one case of vaginal bleeding from endometrial proliferation. CONCLUSION: Local vaginal treatment of 17 beta estradiol (25 microg) had a positive effect on the urogenital symptoms, vaginal pH, and vaginal cytology. No elevation of plasma estradiol level was detected after treatment. PMID- 11759961 TI - Clinical use of erythromycin in children with gastrointestinal dysmotility. AB - Intolerant feeding is a common symptom in gastrointestinal disorders which is commonly found in systemic diseases. Prokinetic drugs play a role in management. A low dose of erythromycin has an effect on improvement of antroduodenal motility and gastric emptying in children and adults. The objective of this study was to evaluate the efficacy of intravenous erythromycin in the treatment of GI dysmotility in children. Retrospective studies were performed in the Department of Pediatrics, Siriraj Hospital, Mahidol University between 1996 and 2000 in 22 patients with intolerance of feeding due to GI dysmotility. Their ages ranged from 11 days to 12 years (42.1 +/- 48.1 months). The patients were divided into 2 groups: 12 critically ill and 10 non-critically ill patients. Dosages of intravenous erythromycin were 1-3 mg/kg/dose every 6 hours. The result of treatment was evaluated as: good (tolerant feeding), fair (tolerant feeding but needing erythromycin for longer than 1 month) and failed (intolerant feeding). All non-critically ill patients had improved symptoms with 9 +/- 4.3 days duration of treatment. In the other group, 8 patients had good results with 10.9 +/- 6 days of treatment. Two patients needed the drug for longer than 1 month and the other 2 patients did not respond and died due to severe infection. Low dose intravenous erythromycin had good efficacy in the treatment of intolerant feeding related to GI dysmotility in children. PMID- 11759962 TI - Ketogenic diet: an alternative treatment for refractory epilepsy in children. AB - RATIONALE: The aim of this study was to establish the first ketogenic diet treatment program for refractory epilepsy in Thailand and to assess its feasibility as well as its efficacy. METHOD: Children with refractory epilepsy were enrolled in the study. This was a prospective open trial study with 35 children (16 boys and 19 girls). Not all patients started on the diet at the same time. Each patient was cumulatively enrolled in this study over the period of 4 years. The mean age on diet was 5.37 +/- 3.57 years (2 months-13 years), mean age of onset of seizures was 19.2 +/- 27.47 months (1 days-8 years), and an average duration on ketogenic diet was 7.67 months (6 days to 29 months). The classic "4:1" formula ketogenic diet was used with some modification. The patient's parents were allowed to improvise and use any fatty diets available in the market such as coconut milk if needed. Parents were closely supervised and instructed on how to prepare the patient's own meals while in the hospital and continued to attend neurology and nutrition clinics. The seizure outcome and side effects were monitored as well as a daily test for urine ketone. RESULTS: At 1 month, 3 months, 6 months, and 12 months duration on the diet, 90 per cent seizure reductions were achieved in 62.5 per cent, 68.18 per cent, 75 per cent, and 66.67 per cent of patients remaining on the diet, respectively. The number of antiepileptic drugs (AEDs) used by each patient also decreased as a result of better seizure control. CONCLUSION: Ketogenic diet can be tried as a management option for refractory epilepsy. It is not difficult to implement even in a developing country like Thailand where resources are limited. It may also help reduce the cost of treatment especially in view of the high prices of the new AEDs. PMID- 11759963 TI - Detection of endometrial cancer in asymptomatic postmenopausal breast cancer patient treated with tamoxifen: a case report. AB - Breast cancer is among the commonest malignancies in women and tamoxifen has been widely used for more than two decades for treatment of breast cancer. It has been known that long term use of tamoxifen significantly increases the risk of endometrial cancer but there is no generally accepted recommendation regarding the surveillance of endometrial pathologies in breast cancer patients taking tamoxifen. Although the incidence of endometrial cancer associated with tamoxifen use is not high, the risk is true and these patients could be helped by screening methods such as transvaginal ultrasonogrphy. We report here a case of endometrial cancer detected by transvaginal 2D scan in an asymptomatic postmenopausal woman taking tamoxifen. PMID- 11759964 TI - Immediate breast reconstruction with free TRAM flap: a case report with a 10-year follow-up and radiological imaging. AB - Immediate breast reconstruction using free microsurgical transverse rectus abdominis flap (free TRAM flap) has been emerging as the recommended treatment for breast cancer patients. Progress of a patient receiving this treatment was documented using a ten-year follow-up study. The results were very satisfactory in both cosmetic appearance and therapeutic result. The surgical techniques of breast mound reconstruction and subsequent nipple and alreolar reconstruction with contralateral mastopexy were described. Mammographic findings of the post reconstruction breast, recommendation for follow-up and the use of mammography were presented. With this successful long-term follow-up, the authors recommend immediate breast reconstruction using free TRAM flap as another option for breast cancer treatment. PMID- 11759965 TI - Mitrofanoff procedure incombination with enterocystoplasty for detrusor hyperreflexia with external sphincter dyssynergia: one-year experience of 12 cases. AB - Twelve patients with the mean age of 35 years who had undergone Mitrofanoff procedure incombination with enterocystoplasty between 1998-1999 were interviewed. All of the patients had suprasacral spinal cord injuries for the mean of 3.5 years from the accident to the operation and failure of medical treatment to suppress hyperreflexic bladder. The vermiform appendix was used to implant as continent stoma in 10 cases and ileal segment was used in 2 cases due to prior appendectomy. The bladder capacity was increased from the mean of 180 ml before the operation to 300 ml intraoperation and 800 ml at 1 year post operation. Up to 1 year, no immediate and late complication was detected except one case who had orchitis at eleven months post-operation. All of them still have continence and self-intermittent catheterization can easily be performed via continent stoma at the abdominal wall. PMID- 11759966 TI - Seizures in myoclonic epilepsy with ragged-red fibers detected by DNA analysis: a case report. AB - A 19-year-old Thai woman presented with progressive ataxia and generalized tonic clonic seizures. Later on, she developed status epilepticus. Blood was tested by molecular DNA analysis which showed A8344G mitochondrial DNA mutation associated with myoclonic epilepsy with ragged-red fibers (MERRF). We confirmed this finding in other members of this family. This is an interesting case report in Thailand of MERRF identified to have A-->G transition mutation at nucleotide 8344 of mitochondrial tRNA(lys) gene without ragged-red fibers from histopathologic studies of muscle. Molecular genetic analysis in suspicious cases of mitochondrial disorders is necessary for proper management and genetic counseling. PMID- 11759967 TI - Microaerophilic streptococcus meningoencephalitis: report of a case. AB - A 64-year-old woman who presented with acute meningoencephalitis was reported. Cerebrospinal fluid (CSF) revealed polymorphonuclear pleocytosis with gram positive cocci. Blood and CSF grew microaerophilic streptococcus. The patient was treated with intravenous penicillin G and chloramphenicol for 2 weeks and recovered without sequela. There was no evidence of any focus of infection prone to the development of this infection. PMID- 11759968 TI - Solitary keratoacanthoma of the conjunctiva: report of a case. AB - Keratoacanthoma characteristically occurs on the skin and is rarely found in the conjunctiva. We, herein, report a case of a healthy 41-year-old Thai woman presenting with a rapidly growing conjunctival mass. The tumor was excised to exclude squamous cell carcinoma. Histopathology revealed a cup shaped well circumscribed proliferation of squamous cells, with a central keratin crater, consistent with a keratoacanthoma. On the literature review, only 12 cases have previously been reported in the English language. The mean age of presentation was 40.75 years, with a male preponderance. Presentation of a mass was mostly within 4 weeks after onset. History of foreign material getting into the eye was positive in 5 cases. All cases were successfully treated by excision, except for one case in which malignancy transformation was found, and enucleation was required eventually. Conjunctival keratoacanthoma is a rare disease. However, this lesion should be well recognized and not misinterpreted as malignancy. As far as we are aware, this is the first report of conjunctival keratoacanthoma from this region. PMID- 11759969 TI - Nodular cutaneous amyloidosis involving the glan penis: report of a case. AB - Nodular cutaneous amyloidosis is a rare disease that predominantly affects women in their sixth and seventh decades. The genital organ is the rarest cutaneous location with only four reported cases of vulvar involvement. We report the first known case of this entity involving the glan penis. The clinical feature of nodular cutaneous amylodosis, the histopathology, the pathogenesis and the therapy are discussed. PMID- 11759970 TI - Are we really managing this HIV patient? PMID- 11759971 TI - Perinatal conditions and early assessment of low-birth-weight premature infants. AB - The developmental assessment of 60 low-birth-weight premature infants, who had no major handicap, was compared with that of 30 term infants at a chronological age of 6 months. Both groups showed no statistically significant differences in mean scores for the Bayley Scales of Infant Development, but the premature group was more likely to have a clinically significant lower function. The premature infants' mental performance had a significantly inverse correlation with the number of days spent in hospital. Follow-up was essential for this group of children in obtaining the early detection of any handicap and performing timely therapeutic intervention. PMID- 11759972 TI - Incidence of type 1 diabetes in children under 15 years in northern Thailand, from 1991 to 1997. AB - The annual incidence of Type 1 diabetes in children under 15 years in northern Thailand from 1991 to 1997 was a retrospective study by analyzing the data gathered from the Pediatric Endocrine Division, Faculty of Medicine, Chiang Mai University and through a mail survey to 202 hospitals in the government and private sector in northern Thailand. The response to the mail survey from 1991 to 1992 and 1993 to 1997 was 90.1 per cent and 94.5 per cent respectively. During the seven year period, 76 new cases of Type 1 diabetes were identified. The crude annual incidence ranged from 0.31-0.56/100,000 per year, with an average incidence of 0.37/100,000 per year (95% C.I. = 0.29-0.46). This very low figure had risen 2.2 fold (over 100%) from that reported in 1984. The annual incidence was relatively constant from 1991 to 1996, although there was a moderate rise in 1997 (0.56/100,000 per year). There was no statistically significant difference between the annual incidence of 1996 and 1997. It remains for further studies to confirm the trend of increased incidence. The median age of onset was 11 years, whereas, the peak age of onset occurred in the 10-14 year age group of both sexes. There was a greater incidence among female in this study. These date confirm the need to develop a national registry of Type 1 diabetes for further epidemiological research. PMID- 11759973 TI - Linear growth in homozygous beta-thalassemia and beta-thalassemia/hemoglobin E patients under different treatment regimens. AB - The effects on linear growth and development among thalassemic patients under different treatment regimens were compared. Twelve homozygous beta-thalassemia (homozygous beta-thal) and 36 beta-thalassemia/Hb E (beta-thal/Hb E) were studied longitudinally between 1977 and 1998. Eighteen cases (10 homozygous beta-thal and 8 beta-thal/Hb E) received hypertransfusion with iron chelation by desferrioxamine. Another 30 cases (2 homozygous beta-thal and 28 beta-thal/Hb E) were given a low transfusion (depending on their clinical requirement). Their heights were measured serially and are presented as a standard deviation score (SDS). There was no significant difference in initial basic hematological data and ferritin levels between either group. However, the hypertransfused group, seemed to be clinically more severely affected than the other group as evidenced by early age at initial transfusion, the early onset of anemia and diagnosis and also their large acquired iron load after a period of transfusion. The average height SDS of the hypertransfused patients was within the 50th percentile +/- 1 SD during the first decade of life in both sexes and both genotypes. Whereas, in patients who were transfused infrequently, the SDS was always below the -1 SD and decreased gradually. In severe beta-thal/Hb E cases, their growth SDS showed no difference from those with homozygous beta-thal. Normal linear growth in those with homozygous beta thal and severe beta-thal/Hb E was only seen in the group that underwent hypertransfusion and this regimen contributed to normal growth during the first ten years of life. However, adequate iron chelation and hormonal treatment in these patients were also required in order to achieve normal adult height. PMID- 11759974 TI - Carbohydrate and electrolyte contents in commercial fruit juices. AB - Forty kinds of commercial fruit juices sold in Thailand were analyzed for types and contents of carbohydrates, electrolytes as well as osmolarity and pH. Each juice was analyzed three times and the results were averaged. A few kinds of fruit juices have high sorbitol contents (> 10 g/L). There are some juices which have a high fructose to glucose ratio (> 1.5:1). Sodium contents in juices ranged from 19 to 1405 mg/L. The osmolarity of the juices ranged from 500 to 1200 mOsmol/L. Most juices have acid pH which ranged between 2.8 and 5.0. It is concluded that each fruit juice has a unique set of properties. Consumers should know the properties of each juice because chronic intake and large amount intake of the juice could have detrimental effects on the health of the consumer. PMID- 11759975 TI - Short and intermediate clinical outcome after late coronary stenting in myocardial infarction. AB - BACKGROUND: The open artery theory has been proposed that late reperfusion of an occluded coronary artery favorably affects clinical outcome. Myocardial reperfusion can be achieved in acute myocardial infarction (AMI) by coronary angioplasty. Coronary stenting improves initial success rate and reduces rate of restenosis. However, there are limited data regarding intermediate outcome of late angioplasty with stenting. METHOD: Between June 1998 and August 1999, one hundred and twenty-three patients with AMI, and forty-four patients (37 males, 7 females) underwent late coronary stenting. Mean age was 57 +/- 10 years. Echocardiography was performed before the procedure and at 6-months follow-up. RESULTS: There were 36 Q-MI and 8 non Q-MI. The infarct-related artery (IRA) was left anterior descending artery (LAD) 55 per cent, left circumflex artery (LCX) 15 per cent, and right coronary artery (RCA) 30 per cent. Coronary stenting was successfully performed in all patients. Pre- and post-procedural diameter stenosis were 90.5 +/- 8.9 per cent and 2.2 +/- 6.5 per cent. Stent indications were suboptimal results (68.2%), intimal dissection (20.4%), and acute closure (11.4%). Over all in-hospital mortality was 2.27 per cent from sudden cardiac death. Mean follow-up was 11.41 +/- 4.79 months. There were 1 MI (2.3%), 2 CHF (4.65%), 1 unstable angina pectoris (2.3%), 1 transient ischemic attack (TIA) (2.3%), and no cardiac death. LVEF showed improvement at 6-months follow-up (47.75 +/- 11.55% vs 54.89 +/- 14.76%, p value < 0.001) CONCLUSION: Late coronary stenting of the IRA of patients with AMI is feasible, with few complications. There was improved LVEF and intermediate clinical outcome. PMID- 11759976 TI - Advanced epithelial ovarian carcinoma in Thai women: should we continue to offer second-look laparotomy? AB - OBJECTIVE: To determine survival among patients with epithelial ovarian carcinoma (EOC) who underwent a second-look laparotomy (SLL) and those refusing the procedure. Also to analyze factor(s) influencing the survival of the patients. METHOD AND MATERIAL: Medical records were reviewed of patients with advanced EOC who were clinically free of disease after primary surgery and platinum-based chemotherapy between January 1, 1992, and December 31, 1998. All of them were offered SLL. Measurement outcomes include patient survival and disease-free survival. RESULTS: There were 50 patients with clinically complete remission after chemotherapy. Sixteen patients underwent SLL, and thirty-four patients refused the procedure (NSLL). Seven patients (43.8%) were reported to have positive SLL. After the median follow-up time of 35 months, 12 patients had died, and 5 patients were lost to follow-up. The median survival time for patients with SLL was about 60 months. Five-year survival rates of patients in the SLL, and NSLL groups were 37 per cent (95%CI = 7%-69%), and 88 per cent (95%CI = 65%-96%) respectively (P<0.001). The median time to relapse was about 25 months for patients with negative SLL. Five-year disease-free survival rates of patients in the negative SLL, and NSLL groups were 28 per cent (95%CI = 4%-59%), and 54 per cent (95%CI = 34%-70%) respectively (P=0.251). By Cox regression analysis, tumor grade was the only significant prognostic factor influencing patients' survival (HR = 6, 95%CI of HR = 1.2-34.2). CONCLUSION: The second-look laparotomy doesn't have a favorable impact on overall and disease-free survival. Tumor grade is the only independent prognostic variable for survival of the patients. PMID- 11759978 TI - Consumer preference study of the female condom in a sexually active population at risk of contracting AIDS. AB - To determine the acceptability of the female condom among commercial sex workers in Khon Kaen, Thailand. Twenty sex workers from a massage parlor and 21 from a brothel were trained in the use of the female condom. The voluntary participants were instructed about the risk of HIV and advised that they could use the female condom as an alternative method to the male condom for protection. The female condom was used in 28.4 per cent and 17.8 per cent episodes of sex in each site during the two weeks. Continuation of use of the female condom increased from 0 per cent in the first group to 43 per cent in the second group. The reasons for discontinuing its use were that it was inconvenient and because of their partners' objection. More users said they liked the female condom even though more thought it was difficult to insert and it did cause pain. However, they would recommend it to others and most felt that other women would want to try it. The participants also saw the advantage of the female condom as a back-up method in case of clients' refusal to use the male condom but all prefered the male condom if there was a choice. PMID- 11759977 TI - Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide dexamethasone-lorazepam in the control of cisplatin induced emesis. AB - The antiemetic effect of ondansetron-dexamethasone-lorazepam versus those of metoclopramide-dexamethasone-lorazepam were evaluated in 30 ovarian cancer patients undergoing treatment with the same chemotherapeutic regimen (cisplatin 60 mg/m2 and cyclophosphamide 700 mg/m2). Patients were randomly selected to receive either the ondansetron arm or the metoclopramide arm in their first cycle of chemotherapy, but were given an alternative combination in the second cycle. In the ondansetron arm, ondansetron was given 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. and lorazepam 0.5 mg oral. For the metoclopramide arm, metoclopramide 10 mg was given i.v. plus dexamethasone 20 mg i.v. and lorazepam 0.5 mg oral. All antiemetics were given twice; 30 minutes before and 6 hours after chemotherapy. In the metoclopramide arm, metoclopramide 40 mg continuous infusion was also administered. During the acute phase, the ondansetron combination was significantly superior to the metoclopramide combination for all evaluation parameters. Complete control of emesis was 90 per cent vs 36.7 per cent, complete protection from nausea was 80 per cent vs 43.3 per cent, and complete protection from both nausea and vomiting was 73.3 per cent vs 30.0 per cent. Forty per cent of patients in the ondansetron arm did not complain of any adverse reaction compared to 13.4 per cent in the metoclopramide arm. It can be concluded, therefore, that a combination of ondansetron, dexamethasone and lorazepam appears to provide a significantly better emetic control with less adverse reaction than the metoclopramide combination in the acute nausea-vomiting phase after receiving cisplatin. PMID- 11759979 TI - Impact of liver cirrhosis on nutritional and immunological status. AB - The aims of the study were to determine the prevalence of protein calorie malnutrition (PCM) in Thai cirrhotic patients and to evaluate nutritional and immunological status in various stages of cirrhosis. Subjective Global Assessment (SGA) and anthropometric measurement were used as nutritional assessment in sixty cirrhotic patients. Delayed-type hypersensitivity skin test, lymphocyte count, immunoglobulin and complement were assessed for immune status. Blood samples were sent for routine tests, prealbumin, thiamine and riboflavin level. There were 7/60 (11.7%) patients with percentage of ideal body weight (%IBW) less than 90 per cent. SGA, hemoglobin, protein indices and cholesterol level showed the deterioration of nutritional status in the late stage of the disease. Five (8.3%) patients with thiamine deficiency, and thirteen (21.7%) patients with riboflavine deficiency were detected. Lowest levels of complement and highest levels of immunoglobulin also occurred in the late stage of the disease. In conclusion, defining %IBW <90 per cent as malnutrition, the prevalence of malnutrition in Thai cirrhotic patients was 11.7 per cent. Nutritional and immunological status deteriorated according to the advanced stage of disease. If nutritional support is given in the early stage, it may improve nutritional status and reduce morbidity and mortality in cirrhotic patients. PMID- 11759980 TI - A comparison between 50 mcg oral misoprostol every 4 hours and 6 hours for labor induction: a prospective randomized controlled trial. AB - OBJECTIVE: To compare the effectiveness and safety between 50 mcg oral misoprostol every 4 hours and 6 hours for labor induction. DESIGN: A prospective randomized controlled trial. SETTING: Department of Obstetrics & Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. SUBJECTS: Eighty nine pregnant women of at least 34 weeks' gestation with indications for labor induction in the condition of unfavourable cervix (Bishop score < or = 4) and no contraindication to prostaglandin therapy. INTERVENTIONS: All pregnant women were randomized to receive either 50 mcg misoprostol orally every 4 hours or 6 hours. MAIN OUTCOME MEASURES: Treatment interval from induction to vaginal delivery, maternal and neonatal complication. RESULTS: The mean treatment intervals from induction to vaginal delivery were 22.10 +/- 18.49 hours and 20.91 +/- 11.98 hours in the misoprostol group every 4 hours and 6 hours, respectively. The treatment intervals between the two groups were not statistically significant. There was also no significant difference between both groups with regard to maternal and neonatal complications. CONCLUSION: The effectiveness in terms of treatment interval from induction to vaginal delivery were comparable between the two groups, but administration of misoprostol every 6 hours was found to have a slightly shorter interval, although it did not reach statistical significance. No serious maternal and neonatal complication was demonstrated in both groups. Either regimen in this study can be an alternative for labor induction. PMID- 11759981 TI - Spontaneous bacterial peritonitis, causes and antibiotic usage in Srinagarind hospital. AB - Spontaneous bacterial peritonitis (SBP) is a common and often fatal complication occurring in cirrhotic patients with ascites. It is defined as an infection of the ascitic fluid in the absence of any obvious intra-abdominal source. This study was a descriptive retrospective study that examined signs and symptoms of SBP, prevalence, result of the culture and antibiotic susceptibility of the organisms and outcome of antibiotic treatment, especially to ampicillin aminoglycoside. Data were collected from inpatient medical records at Srinagarind Hospital between 1993 and 1997. Forty-four patients with 54 episodes of SBP were included in this study. The results revealed that SBP commonly occurred in cirrhotic patients. Presenting symptoms of SBP were fever, abdominal pain and abdominal distension, respectively. Signs of SBP were ascites and rebound abdominal tenderness. Forty-three per cent of ascitic fluid cultures were positive for bacteria E. coli (30.4%), Streptococcus spp (26.1%) and Klebsiella spp (13.0%) were the most common causes of SBP which were similar to other studies. Ampicillin plus an aminoglycoside were mostly often used in this study; in only 15.8 per cent of patients did the antibiotics need to be changed. Mortality rate in this group was not increased after antibiotic was changed. PMID- 11759982 TI - Research program opens doors of Russian biomedical facilities to U.S. veterinarians. PMID- 11759983 TI - Disagrees with alternative view of separation anxiety. PMID- 11759984 TI - Grateful for show of support following terrorist attacks. PMID- 11759985 TI - What is your diagnosis? A lobular, periarticular, mineralized soft-tissue opacity in the region of the subscapularis muscle. PMID- 11759986 TI - Determining success competencies. PMID- 11759987 TI - Anesthesia case of the month. Partial obstruction of the trachea was a differential diagnosis for the bird's respiratory problems. PMID- 11759988 TI - American College of Zoological Medicine recommendations on veterinary curricula. PMID- 11759989 TI - Role of dietary carbohydrate and fat in horses with equine polysaccharide storage myopathy. PMID- 11759990 TI - Veterinary practice expenses and financial ratios. PMID- 11759991 TI - Negligence in restraint. PMID- 11759992 TI - Effects of platelet clumping on platelet concentrations measured by use of impedance or buffy coat analysis in dogs. AB - OBJECTIVE: To determine whether platelet clumps are homogeneously distributed in blood samples, and whether platelet concentrations (PC) obtained by use of impedance and buffy coat analysis can be considered minimum values when platelet clumps are present. DESIGN: Prospective study. SAMPLE POPULATION: 50 blood samples obtained from 30 dogs. PROCEDURE: 10 blood samples containing platelet clumps were used and 10 smears were made from each sample; amount of platelet clumping was graded for all 100 smears. Blood from each of 20 healthy dogs was divided between 2 EDTA tubes before and after platelet clumping was induced by adenosine diphosphate (ADP). The PC for each ADP-treated and untreated sample were measured, using impedance and quantitative buffy coat analyzers. RESULTS: Platelet clumps were evident in all 100 blood smears, but the amount of clumping varied considerably within some samples. Using the impedance analyzer, the PC of ADP-treated samples were significantly lower and never higher than the PC of untreated samples. Using the buffy coat analyzer, some ADP-treated samples had increased PC; however, significant differences were not detected between treated and untreated samples. CONCLUSIONS AND CLINICAL RELEVANCE: Platelet clumping was not homogeneous within blood samples. When platelet clumps were identified by direct examination of blood smears, the PC detected by use of the impedance analyzer could be considered minimum values. In contrast, the PC detected by use of the buffy coat analyzer were sometimes increased. Useful information can be obtained by measuring PC in blood with platelet clumps; values obtained by use of impedance can be considered minimums, and values obtained by use of buffy coat analysis may be either minimum values or reasonable estimates of PC. PMID- 11759993 TI - Effects of a selective serotonin reuptake inhibitor on urine spraying behavior in cats. AB - OBJECTIVE: To determine the effectiveness of a readily available selective serotonin reuptake inhibitor (SSRI), fluoxetine hydrochloride, on reducing problem urine spraying in cats. DESIGN: Randomized placebo-controlled double blind clinical trial. ANIMALS: 17 neutered cats > 1 year old with objectionable urine spraying behavior. Procedure-Owners recorded urine-spraying events for 2 weeks (baseline). Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine or fish-flavored liquid placebo. If urine spraying was not reduced by 70% by weeks 4 through 5, the dosage was increased by 50% for weeks 7 and 8. After discontinuation of treatment at the end of 8 weeks, owners recorded daily urine marks for another 4 weeks. RESULTS: The mean (+/- SE) weekly rate of spraying episodes in treated cats was 8.6 (+/- 2.0) at baseline, decreased significantly by week 2 (1.7 +/- 0.6), and continued to decrease by weeks 7 and 8 (0.4 +/- 0.2). The mean weekly spraying rate of cats receiving placebo was 7.8 (+/- 1.5) at baseline, decreased only slightly during week 1 (5.5 +/- 1.8), and did not decline further. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. The frequency of spraying before treatment is predictive of the spraying rate when the drug is discontinued. PMID- 11759995 TI - Mineralized corneal sequestrum in a cat. AB - An 8-month-old 3-kg (6.6-lb) sexually intact male cat was evaluated for chronic refractory keratitis and a corneal plaque that developed after treatment with a corticosteroid-containing ophthalmic preparation. Pertinent ophthalmic findings included blepharospasm, conjunctivitis, corneal vascularization, and a tan raised corneal plaque with a dense and gritty composition. Lamellar keratectomy was performed to excise the plaque. The cornea healed with mild scarring. Histologic examination revealed extensive coagulation necrosis and mineralization of the corneal stroma with increased inflammatory cells, blood vessels, and fibrosis, which is compatible with a diagnosis of mineralized corneal sequestrum. The history suggested chronic feline herpesvirus-1 (FHV-1)-induced keratoconjunctivitis as the underlying cause. Topical corticosteroid administration may have potentiated the preexisting corneal necrosis and initiated mineralization. To our knowledge, mineralization of a corneal sequestrum in a cat has not been reported in a clinical case but has been reported in cats experimentally infected with FHV-1. PMID- 11759996 TI - Inadvertent severe hypercarbia associated with anesthesia machine malfunction in one cat and two dogs. AB - Severe acute hypercarbia occurred in a cat and 2 dogs as a result of anesthesia machine malfunction. In each case, the anesthesia machine had been checked by the anesthesia technician and clinician, and no problems were found. After it was noticed that the same machine had been used on each animal, further investigation revealed an expiration valve that was functional with large breaths or positive pressure ventilation but was not functional with small breaths with low peak inspiratory flow. Rebreathing of expired carbon dioxide occurred, and the patients subsequently became severely hypercarbic. Recovery from anesthesia was prolonged in 2 animals, and cardiac and respiratory arrest occurred in the third. Hypercarbia from rebreathing can be detected through the use of blood gas analysis or end-tidal carbon monoxide monitoring. PMID- 11759994 TI - Radiosurgery using a stereotactic headframe system for irradiation of brain tumors in dogs. AB - Radiation therapy of brain tumors in dogs typically involves administration of multiple fractions over several weeks. Fractionation is used to minimize damage to normal tissue. Radiosurgery uses multiple non-coplanar stereotactically focused beams of radiation in a series of arcs to deliver a single dose to the target with extreme accuracy. The large number of beams facilitates a high degree of conformation between the treatment area and the target tumor and allows for a steep dose gradient; the use of nonintersecting arcs minimizes exposure of normal tissue. Computed tomography with a stereotactic localizer secured to the skull allows generation of a 3-dimensional image of the target and provides accurate spatial coordinates for computerized treatment planning and delivery. Three dogs were treated with radiosurgery, using 1,000 to 1,500 cGy. A linear accelerator mounted on a rotating gantry was used to generate and deliver the radiation. Two dogs with meningiomas survived 227 and 56 weeks after radiosurgery. A dog with an oligodendroglioma survived 66 weeks. No complications were observed following the use of this technique. PMID- 11759997 TI - Episioplasty for the treatment of perivulvar dermatitis or recurrent urinary tract infections in dogs with excessive perivulvar skin folds: 31 cases (1983 2000). AB - OBJECTIVE: To evaluate the effectiveness of episioplasty for the treatment of perivulvar dermatitis or chronic or recurrent urinary tract infections (UTI) believed to be secondary to excessive perivulvar skin folds in dogs and to document whether a causal relationship exists between the presence of chronic or recurrent UTI and excessive perivulvar skin folds in female dogs. DESIGN: Retrospective study. ANIMALS: 31 female dogs. PROCEDURE: Medical records of dogs with vulvar dermatitis (group 1; n = 15) or UTI (group 2; 16) were reviewed for history, signalment, physical examination findings, hematologic findings, results of urine or vaginal bacteriologic culture, and results of additional diagnostic procedures. RESULTS: 14 of 15 dogs in group 1 had complete resolution of perivulvar dermatitis and associated clinical signs following episioplasty. One dog had a relapse of clinical signs and vulvar dermatitis 2 years after surgery in association with a 9-kg (1 9.8-1b) weight gain. Sixteen of 16 dogs in group 2 had complete resolution of clinical signs of UTI following episioplasty. Urine samples were obtained via cystocentesis no earlier than 1 month after surgery to confirm resolution of UTI in 13 of 16 of dogs in group 2. Mild-to-moderate incisional swelling was the only surgical complication reported for either group, with the exception of 1 dog in group 2 that had wound dehiscence. All owners were satisfied with surgical outcomes. CONCLUSIONS AND CLINICAL RELEVANCE: All owners reported complete resolution of clinical signs for both groups of dogs. Episioplasty is an effective low morbidity treatment for perivulvar dermatitis and chronic UTI associated with excessive perivulvar skin folds. PMID- 11759998 TI - Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996-2000). AB - OBJECTIVE: To evaluate responses of cats with vaccine-associated sarcomas to treatment with surgery and radiotherapy, with or without adjunctive chemotherapy. DESIGN: Retrospective study. ANIMALS: 76 cats (78 tumors). PROCEDURE: Medical records were reviewed. Factors potentially associated with survival time, time to recurrence, and time to development of metastases were evaluated. RESULTS: Following excision, electron beam radiation, and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine-associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate. PMID- 11759999 TI - Treatment of chronic pleural effusion with pleuroperitoneal shunts in dogs: 14 cases (1985-1999). AB - OBJECTIVE: To describe complications and outcome associated with chronic nonseptic pleural effusion treated with pleuroperitoneal shunts in dogs. DESIGN: Retrospective study. ANIMALS: 14 dogs. PROCEDURE: Medical records at 4 veterinary schools were examined to identify dogs with chronic nonseptic pleural effusion that were treated by use of a pleuroperitoneal shunt between 1985 and 1999. Signalment, history, physical examination and laboratory findings, cause and type of pleural effusion, medical and surgical treatments, complications, and outcome were reviewed. RESULTS: 10 of 14 dogs had idiopathic chylothorax, and 4 had an identified disease. All but 1 dog with idiopathic chylothorax and 1 dog with chylothorax from a heart base tumor had unsuccessful thoracic duct ligation prior to pump placement. No intraoperative complications developed during shunt placement. Short-term complications developed in 7 of 13 dogs, necessitating shunt removal in 2 dogs and euthanasia in 1. Eight of 11 dogs with long-term follow-up developed complications; the overall mean survival time and the interval in which dogs remained free of clinical signs of pleural effusion were 27 months (range, 1 to 108 months) and 20 months (range, 0.5 to 108 months), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pleuroperitoneal shunts can effectively palliate clinical signs associated with intractable pleural effusion in dogs. Numerous short- and long-term complications related to the shunt should be expected. Most complications can be successfully managed, but even when shunts are functional some treatments fail because of severe abdominal distension or massive pleural fluid production that overwhelms the functional capacity of the shunt. PMID- 11760000 TI - The connectivity index 25 years after. AB - We review the developments following introduction of the connectivity indices as molecular descriptors in multiple linear regression analysis (MLRA) for structure property-activity studies. We end the review with discussion of results obtained with applications of the variable connectivity index. A comparison is made between some results obtained with the traditional topological indices and the variable connectivity index. PMID- 11760001 TI - Molecular structure-property relationships for alkenes. AB - Structure-property relationships were obtained for 11 physical and chemical properties (boiling points (bp), melting points (mp), molar refractions (MR), molar volumes (MV), heats of combustion (HCKJ), molar heats of vaporization (HVMOL), flashpoints (FLASHK), second virial coefficients (VIRC2), critical temperatures (Tc), critical pressures (Pc), and viscosities (VISC)) for a data set consisting of 162 C4-C9 monoalkenes. Both molecular connectivity indices and ad hoc descriptors were tested as structural descriptors, and both produced high quality regression equations for most of the properties. As was observed in an earlier study of alkanes [J. Am. Chem. Soc. 110 (1988) 4186], mp were not well described by either descriptor set. For most properties, the mass/bulk of the molecule was found to be the most important structural feature determining the property, suggesting that dispersion forces play a dominant role in determining those properties influenced by intermolecular interactions. The amount of branching in the molecule and the nature of the double bond environment were also found to be influential features. PMID- 11760002 TI - Issues in representation of molecular structure the development of molecular connectivity. AB - Significant issues in the representation of molecular structure and the development of the molecular connectivity paradigm are presented. In the molecular connectivity paradigm, molecular structure is represented directly. Kier and Hall developed the method by creating ways to encode electronic information based on the paradigm developed from the Randic branching index. The simple and valence delta values were created to encode atomic and valence-state electronic information through counts of sigma, pi, and lone pair electrons. A family of indices was created to provide a wide range of structure information. The key aspects of the development are presented and discussed in such a way as to reveal, at least in part, the imaginative thinking involved in the process. Possible future roles for molecular connectivity chi indices are discussed. PMID- 11760003 TI - Novel local (fragment-based) topological molecular descriptors for QSpr/QSAR and molecular design. AB - Novel molecular descriptors based on local spectral moments of the bond matrix are defined. Mathematical expressions relating bond moments to linear combinations of structural fragments are derived. The novel descriptors are used to describe boiling points of alcohols producing a good QSPR model accounting for more than 98% of variance. A quantitative structure-reactivity model is obtained to predict the specific rate constant (log k) of the nucleophilic addition of mercaptoacetic acid to 2-furylethylene derivatives. The model accounts for more than 96% of the variance in log k. Two other models were also obtained by using molecular connectivity indices and total spectral moments of the bond matrix that account for <84% of the variance in this reactivity index. A model based on quantum chemical descriptors accounts for the same variance than that obtained with bond moments. The model based on local moments permitted to compute the contribution of different structural fragments to the reactivity, and a good relationship (r = 0.98) was obtained with these group contributions with Hammett sigma(p) constants for 21 groups. PMID- 11760004 TI - Overall connectivity--a next generation molecular connectivity. AB - The development of molecular connectivity concept and some of its key elements - Randic's inverse-square-root function and the detailed subgraph characterization are analyzed. The concept of overall connectivity recently advanced is presented as a next step in unfolding the ideas of molecular connectivity by combining them with those of molecular complexity. Definitions of overall connectivity index, eth-order overall connectivities, and overall connectivity vector are presented along with formulae for calculating these sets of topological indices for several classes of graphs of chemical relevance. Based on sums of adjacencies over all subgraphs (or up to a limiting subgraph size in large molecules), the overall connectivities increase both with molecule size and complexity, as expressed in branching and cyclicity of molecular skeleton. When applied to molecules containing heteroatoms, valence overall connectivities are constructed employing the Kier and Hall scheme. The usefulness of the novel indices is demonstrated by modeling physicochemical properties of alkane compounds. A detailed comparison is made with other models derived for the same set of compounds, proceeding from molecular connectivity, as well as with two other probe connectivity functions- the overall connectivity versions of the second Zagreb index, and a derivative inverse function of this index. The favorable comparisons indicate the need of molecular connectivity paradigm revisiting, and show the potential of the overall connectivity indices for QSPR/QSAR applications. PMID- 11760005 TI - Molecular connectivity: intermolecular accessibility and encounter simulation. AB - The simple molecular connectivity indices are interpreted as summations of bond accessibilities to bimolecular encounters with another, identical molecule. To transcend this model, a molecule is treated as disjecta membra with each bond modeled as a discrete cell in a dynamic simulation of many molecules. Each bond accessibility is transformed into a cellular automata rule. The dynamics are run for each of 38 alkanes, recording the average number of cell encounters, beta. The beta values show a high correlation with the boiling points. The significance of the bond accessibilities and the concept of intermolecular encounters explaining the molecular connectivity indices is supported by these findings. PMID- 11760006 TI - General topological patterns of known drugs. AB - Discriminating "drug-like" from "non-drug-like" compounds is a relatively emerging topic within the drug research. The basic assumption is that it is possible to obtain relevant information from structural features common to the known drugs, in order to discard a huge number of candidate chemical structures with low probability of becoming drugs. A graph-theoretical contribution to this subject is reported in this paper, by making exclusive use of linear relationships. The results suggest that it is possible to achieve a pattern of general pharmacological activity based on molecular topology. Conclusions are tentative pending verification of the results with larger compound libraries. PMID- 11760007 TI - Molecular similarity-based estimation of properties: a comparison of three structure spaces. AB - Similarity, like beauty, is an intuitive concept based on personal perception and bias. In the realm of molecular similarity, each method is user defined based on the features deemed important. A method's efficacy depends on the set of descriptors used to define the intermolecular similarity of chemicals and on the mathematical function used to quantify similarity. Quantitative molecular similarity analysis (QMSA) methods, based on experimental data or computed molecular descriptors, have emerged as powerful tools for analog selection and property estimation. We have carried out a comparative study of similarity spaces derived from atom pairs and a large set of topological indices for two diverse sets of chemicals: (a) a set of 469 chemicals with vapor pressure data from the TSCA inventory, and (b) a set of 213 chemicals with lipophilicity data from the STARLIST inventory. These spaces were used for the KNN-based estimation of properties (K = 1-10, 15, 20, 25). The results for the QMSA models developed in this paper are also compared with model estimates derived from hierarchical QSARs. PMID- 11760008 TI - Pebbles of truth. PMID- 11760009 TI - Clockless yeast and the gears of the clock: how do they mesh? AB - In spite of its apparent weakness as a clock model, the budding yeast has spawned a technique that has revolutionized our ability to study specific protein-protein interactions like those at the core of the molecular timekeeping mechanisms. Here, the author will summarize the evolution, power, and limitations of this technique and highlight its potential and actual contributions to the field of chronobiology. PMID- 11760010 TI - Resetting of the circadian clock by phytochromes and cryptochromes in Arabidopsis. AB - The authors sought to investigate the role of phytochromes A and B (phyA and phyB) and cryptochromes 1 and 2 (cryl and cry2) in the synchronization of the leaf position rhythm in Arabidopsis thaliana. The seedlings were transferred from white light-dark cycles to free-running conditions with or without exposure to a light treatment during the final hours of the last dark period. The phase advance caused by a far-red light treatment was absent in the phyA mutant, deficient in the fhy1 and fhy3 mutants involved in phyA signaling, and normal in the cryl and cryl cry2 mutants. The phase shift caused by blue light was normal in the cry2 mutant; reduced in the phyA, cryl, phyA cry1, and cry1 cry2 mutants; and abolished in the phyA cryl cry2 triple mutant. The phase shift caused by red light was partially retained by the phyA phyB double mutant. The authors conclude that cryl and cry2 participate as photoreceptors in the blue light input to the clock but are not required for the phyA-mediated effects on the phase of the circadian rhythm of leaf position. The signaling proteins FHY1 and FHY3 are shared by phyA-mediated photomorphogenesis and phyA input to the clock. PMID- 11760012 TI - Daily novel wheel running reorganizes and splits hamster circadian activity rhythms. AB - The phenomenon of splitting of locomotor activity rhythms in constant light has implied that the mammalian circadian pacemaker is composed of multiple interacting circadian oscillators. Exposure of male Syrian hamsters to novel running wheels also induces splitting in some reports, although novel wheel running (NWR) is better known for its effects on altering circadian phase and the length of the free-running period. In three experiments, the authors confirm and extend earlier reports of split rhythms induced by NWR. Male Syrian hamsters, entrained to LD 14:10, were transferred for 6 to 11 consecutive days to darkened novel Wahmann wheels at ZT 4 and were returned to their home cages at ZT 9. All hamsters ran robustly in the novel wheels. NWR caused a marked reorganization of home cage wheel-running behavior: Activity onsets delayed progressively with each additional day of NWR. After 11 days, activity onset in the nighttime scotophase was delayed by 7 h and disappeared completely in 2 hamsters (Experiment 1). After 6 to 7 days of NWR (Experiment 2), activity onset delayed by 5 h. Transfer of hamsters to constant darkness (DD) after 7 days of NWR revealed clearly split activity rhythms: The delayed nighttime activity bout was clearly identifiable and characterized by a short duration. A second bout associated with the former time of NWR was equally distinct and exhibited a similarly short duration. These components rejoined after 3 to 5 days in DD accomplished via delays and advances of the nighttime and afternoon components, respectively. The final experiment established that rejoining of activity components could be prevented by perpetuating the light-dark:light-dark cycle used to induce split rhythms. The data suggest that NWR causes selective phase shifting of some circadian oscillators and that component oscillators interact strongly in constant darkness. PMID- 11760013 TI - Temporal reorganization of the suprachiasmatic nuclei in hamsters with split circadian rhythms. AB - A dual oscillator basis for mammalian circadian rhythms is suggested by the splitting of activity rhythms into two components in constant light and by the photoperiodic control of pineal melatonin secretion and phase-resetting effects of light. Because splitting and photoperiodism depend on incompatible environmental conditions, however, these literatures have remained distinct. The refinement of a procedure for splitting hamster rhythms in a 24-h light dark:light-dark cycle has enabled the authors to assess the ability of each of two circadian oscillators to initiate melatonin secretion and to respond to light pulses with behavioral phase shifting and induction of Fos-immunoreactivity in the suprachiasmatic nuclei (SCN). Hamsters exposed to a regimen of afternoon novel wheel running (NWR) split their circadian rhythms into two distinct components, dividing their activity between the latter half of the night and the afternoon dark period previously associated with NWR. Plasma melatonin concentrations were elevated during both activity bouts of split hamsters but were not elevated during the afternoon period in unsplit controls. Light pulses delivered during either the nighttime or afternoon activity bout caused that activity component to phase-delay on subsequent days and induced robust expression of Fos-immunoreactivity in the SCN. Light pulses during intervening periods of locomotor inactivity were ineffective. The authors propose that NWR splits the circadian pacemaker into two distinct oscillatory components separated by approximately 180 degrees, with each expressing a short subjective night. PMID- 11760011 TI - Distinct pharmacological mechanisms leading to c-fos gene expression in the fetal suprachiasmatic nucleus. AB - Maternal treatment with cocaine or a D1-dopamine receptor agonist induces c-fos gene expression in the fetal suprachiasmatic nuclei (SCN). Other treatments that induce c-fos expression in the fetal SCN include caffeine and nicotine. In the current article, the authors assessed whether these different pharmacological treatments activate c-fos expression by a common neurochemical mechanism. The results indicate the presence of at least two distinct pharmacological pathways to c-fos expression in the fetal rat SCN. Previous studies demonstrate that prenatal activation of dopamine receptors affects the developing circadian system. The present work shows that stimulant drugs influence the fetal brain through multiple transmitter systems and further suggests that there may be multiple pathways leading to entrainment of the fetal biological clock. PMID- 11760014 TI - Light-Induced resetting of the circadian pacemaker: quantitative analysis of transient versus steady-state phase shifts. AB - The suprachiasmatic nuclei of the hypothalamus contain the major circadian pacemaker in mammals, driving circadian rhythms in behavioral and physiological functions. This circadian pacemaker's responsiveness to light allows synchronization to the light-dark cycle. Phase shifting by light often involves several transient cycles in which the behavioral activity rhythm gradually shifts to its steady-state position. In this article, the authors investigate in Syrian hamsters whether a phase-advancing light pulse results in immediate shifts of the PRC at the next circadian cycle. In a first series of experiments, the authors aimed a light pulse at CT 19 to induce a phase advance. It appeared that the steady-state phase advances were highly correlated with activity onset in the first and second transient cycle. This enabled them to make a reliable estimate of the steady-state phase shift induced by a phase-advancing light pulse on the basis of activity onset in the first transient cycle. In the next series of experiments, they presented a light pulse at CT 19, which was followed by a second light pulse aimed at the delay zone of the PRC on the next circadian cycle. The immediate and steady-state phase delays induced by the second light pulse were compared with data from a third experiment in which animals received a phase-delaying light pulse only. The authors observed that the waveform of the phase-delay part of the PRC (CT 12-16) obtained in Experiment 2 was virtually identical to the phase-delay part of the PRC for a single light pulse (obtained in Experiment 3). This finding allowed for a quantitative assessment of the data. The analysis indicates that the delay part of the PRC-between CT 12 and CT 16-is rapidly reset following a light pulse at CT 19. These findings complement earlier findings in the hamster showing that after a light pulse at CT 19, the phase advancing part of the PRC is immediately shifted. Together, the data indicate that the basis for phase advancing involves rapid resetting of both advance and delay components of the PRC. PMID- 11760015 TI - Temperature cycles induce a bimodal activity pattern in ruin lizards: masking or clock-controlled event? A seasonal problem. AB - The daily locomotor activity pattern of Ruin lizards in the field is mainly unimodal, except for summer months when soil temperatures exceed 40 degrees C to 42 degrees C around midday. In such a situation, lizards reduce their locomotor activity around midday to avoid overheating, and thus their daily activity pattern becomes bimodal. The bimodal pattern expressed in the field is usually retained in the free-running rhythm under constant temperature and DD for a couple of weeks, after which the bimodal pattern changes into a unimodal pattern. In the present study, the authors examined whether 24-h temperature cycles (TCs) would change lizard activity from a unimodal to a bimodal pattern. Administration of TCs to unimodal lizards free-running in DD is able to entrain locomotor rhythms and to induce a bimodal pattern both in summer and autumn-winter. There are, however, striking seasonal differences in the effectiveness with which TCs achieve bimodality: (a) Numbers of lizards rendered bimodal are significantly higher in summer than in autumn-winter; (b) TCs require less time to achieve bimodality in summer than autumn-winter; (c) bimodality is retained as an aftereffect in the postentrainment free-run in summer, but not in autumn-winter; (d) TCs change activity duration in summer, but not in autumn-winter. All this demonstrates the existence of seasonal changes in responsiveness of the circadian oscillators controlling activity to the external factors inducing bimodality. Oscillators' responsiveness is high in summer, when bimodality is the survival strategy of Ruin lizards to avoid overheating around midday in open fields, and low in autumn-winter, when bimodality has no recognizable adaptive significance. PMID- 11760016 TI - Persistence of masking responses to light in mice lacking rods and cones. PMID- 11760017 TI - Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta. AB - A prospective open study was performed to determine the efficacy and safety of pamidronate in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta (OI). Intravenous pamidronate was administered at 1.5 mg/kg bi-monthly to six children with OI, over 12-23 months. The number of fractures decreased from median of 3 (range 1-12) to 0 fractures/year (range 0-4) (P<0.05). After 12 months of treatment, there was significant improvement in areal bone mineral density (BMD) z-scores of the lumbar spine from median of 2.40 (range -3.20 to -1.67) to -1.90 (range -2.38 to -0.91) (P<0.05) and in the volumetric BMD which increased from median of 0.095 to 0.146 g/cm3 (P<0.05). Urine N-telopeptide levels (bone resorption marker) decreased from a median of 461.5 bone collagen equivalent/creatinine (BCE/Cr) (range 129-721 BCE/Cr) to 223.5 BCE/Cr (range 107-312 BCE/Cr) (P<0.05) and serum alkaline phosphatase (ALP) (bone formation marker) from a median of 230.0 U/l (range 148-305 U/l) to 133.5 U/l (range 79-233 U/l) (P<0.05), reflecting reduced bone turnover. This may represent a net reduction in bone resorption and provides a biochemical explanation for the increase in bone mineralisation. Height standard deviation scores were not affected and there were no significant adverse effects. CONCLUSION: 1 year cyclical pamidronate is effective and safe in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta. PMID- 11760018 TI - Late clinical manifestation of cerebral tuberculomas in two children with tuberculous meningoencephalitis. AB - We report on two children with cerebral tuberculomas leading to late dramatic clinical exacerbation after appropriate antituberculous chemotherapy and high dose corticosteroids. A 6-year-old girl with tuberculous meningoencephalitis initially fully recovered. However, after 9 months of continuous therapy she presented with acute increased intracranial pressure caused by tuberculomas requiring rapid drainage of CSF. A 16-year-old boy with miliary pulmonary tuberculosis and severe meningoencephalitis had reached a stable condition for more than 10 months although still suffering from a left-dominant spasticity and motor dysphasia. Fifteen months after initiation of therapy he presented with an acute central paralysis of the left facial nerve, progressive hemiplegia, severe ataxia and increasing lethargy caused by a cerebral tuberculoma with a perifocal oedema. Prolonged treatment with antituberculous chemotherapy and high-dose corticosteroids led to complete recovery in the younger patient and marked improvement in the older patient who remains severely handicapped. CONCLUSION: Patients with initially successful treatment of central nervous system tuberculosis should undergo an alert follow-up for the development of late cerebral tuberculomas. Treatment should consist of prolonged courses of antituberculous chemotherapy and high-dose corticosteroids. PMID- 11760019 TI - Nail matrix arrest in the course of hand, foot and mouth disease. AB - Onychomadesis describes complete nail shedding from the proximal portion; it is consecutive to a nail matrix arrest and can affect both fingernails and toenails. It is a rare disorder in children. Except for serious generalised diseases or inherited forms, most cases are considered to be idiopathic. Few reports in literature concern common triggering phenomena. We present four patients in whom the same benign viral condition in childhood appeared as a stressful event preceding onychomadesis. In each case, spontaneous complete healing of the nails was achieved within a few weeks. CONCLUSION: Onychomadesis and/or onycholysis is a newly recognised complication in the course of viral infections presenting clinically as hand, foot and mouth disease, and because of mild forms, is probably underestimated. PMID- 11760020 TI - A novel mutation in the anti-mullerian hormone gene as cause of persistent mullerian duct syndrome. AB - Persistent mullerian duct syndrome is a relatively rare inherited defect of sexual differentiation characterised by failure of regression of the mullerian ducts in males. In affected individuals, uterus and tubes are present because of defects of synthesis or action of anti-mullerian hormone (AMH), normally produced by the Sertoli cells of the testis. Patients are normally virilised, although mono- or bilateral cryptorchidism may be present. We observed two brothers (chromosomes 46 XY), aged 11 years and 2 months and 8 years and 3 months respectively, with bilateral cryptorchidism. The diagnosis of persistent mullerian duct syndrome was made on the basis of laparoscopic evidence of uterus and tubes, undetectable plasma levels of AMH and a 23 base pair duplicative insertion in exon 5 of the AMH gene, causing the introduction of a premature stop codon, homozygous in the two brothers. The surgical correction of the genital abnormalities was successfully carried out by laparoscopic orchidopexy according to Fowler-Stephens. CONCLUSION: Persistent mullerian duct syndrome should be taken into consideration in all cases of bilateral cryptorchidism. Laparoscopy is the elective procedure for diagnosis of this disease and laparoscopic surgery for orchidopexy of intra-abdominal testes. Mutation analysis of the anti-mullerian hormone gene in these patients helps to understand the structure-function relationship of the anti-mullerian hormone protein, although it is not clear at present whether anti-mullerian hormone is necessary to maintain normal testicular function. PMID- 11760021 TI - Anomalies of the abdominal aorta in Williams-Beuren syndrome--another cause of arterial hypertension. AB - Vascular disease in Williams-Beuren syndrome is based on an elastin arteriopathy which may cause stenoses in small and great vessels. This study presents the pattern of stenotic lesions of the abdominal aorta and the incidence of arterial hypertension. From 112 patients with Williams-Beuren syndrome followed since 1975, 25 patients were studied by aortography. The diameter of the thoracic aorta and the change in diameter to the iliac bifurcation were compared with normal data. Renal artery stenosis was suspected when the proximal vessel diameter was less than 50% of the distal diameter. Of the 25 patients, 20 had vascular stenosis of whom 19 patients were affected by segmental narrowing either of the thoracic aorta (n=9) or the abdominal aorta (n = 7) or both (n = 3). Hypoplasia of the abdominal aorta was characterised by the smallest diameters at the renal artery level and an increased diameter of the infrarenal abdominal aorta. A total of 11 patients had renal arterial stenosis, associated with narrowing of other aortic segments in 10 cases. Only one patient had a solitary stenosis of the renal artery. Arterial hypertension was diagnosed in 17 patients, 2 of them had no vascular lesions; in the remaining 15 patients stenosis was present in more than one segment (aorta 6, renal artery stenosis 1, both 8). CONCLUSION: Narrowing of the abdominal aorta in patients with Williams-Beuren syndrome is a frequent morphological manifestation of the arteriopathy. Isolated renal arterial stenosis was rare, since it was more frequently combined with a narrowed aorta. Hypertension is a common symptom in the affected group and must be regarded as a manifestation of generalised arteriopathy rather than renal hypoperfusion. PMID- 11760022 TI - Recurrent facial nerve palsy in paediatric patients. AB - The aim of the study was to investigate the clinical presentation and prognosis of recurrent facial nerve palsy (RFNP) in children. The files of 182 patients referred to the Schneider Children's Medical Centre of Israel for neurological evaluation of isolated peripheral facial nerve palsy between October 1992 and December 1998 were reviewed. RFNP was found in 11 patients (9 females, 2 males), with an incidence of 6%. In two males, the aetiology was traced to Melkersson Rosenthal syndrome and these patients were separated from the rest of the group. Three children had two episodes of facial nerve paresis which completely resolved clinically within several weeks. Six other children underwent electrophysiological studies. Two of the latter with residual neurological damage, and one child with abnormal blink reflex only, showed decreased facial nerve conduction velocity and abnormal blink reflex. Three children with complete recovery had disturbed blink reflex only with normal nerve conduction. Brain imaging studies as well as laboratory work-up were non-contributory in all cases. CONCLUSION: The frequency of recurrent facial nerve palsy in children was similar to that in adults. The most significant factors in the evaluation of recurrent facial nerve palsy are medical history and physical findings at diagnosis and after short follow-up. In our patients, electrophysiological studies did not have either clinical or prognostic significance. The rate of full clinical recovery is about 70%, lower than in Bell palsy. PMID- 11760023 TI - Report and review of the fetal brain disruption sequence. AB - The fetal brain disruption sequence (FBDS), a rare cause of extreme microcephaly, is described in a patient and compared with 19 previously reported cases. Clinical findings present in almost all patients included: severe microcephaly (average occipitofrontal circumference -5.8 SD), overlapping sutures, prominent occipital bone, scalp rugae with normal hair patterning and marked neurological impairment. Early death occurred in 7/20 cases. The FBDS was sporadic in 17 out of 19 reported cases supporting a low recurrence risk for genetic counselling purposes. A group of related observations in cases were thromboembolic phenomenon following death of the co-twin, vascular and/or haematological involvement by prenatal cytomegalovirus infection, prenatal cocaine exposure, direct vascular fetal trauma (cordocentesis) and fetal vascular changes after a maternal car accident causing intracranial bleeding and brain damage. Normal scalp hair pattern in all cases and the second or third trimester location of the disruptive event in two cases suggest that in the FBDS, brain growth is normal throughout the first 18 weeks of gestation at least. CONCLUSION: Pathogenic factors suggest that different forms of vascular injury to the fetal brain (emboli, haemorrhage, vasoconstriction, disseminated intravascular coagulation) can produce partial brain destruction, diminished intracranial pression and skull collapse in the fetal brain disruption sequence. PMID- 11760024 TI - Correction of length discrepancies and angular deformities of the leg by Blount's epiphyseal stapling. AB - The management of leg length difference (LLD) and angular deformities of the leg remains controversial. Numerous treatment options have been proposed over the past years depending on the patient's general condition, skeletal age, function, and degree and configuration of the deformity. Our retrospective study consisted of 48 patients with 58 legs treated between 1970 and 1991 by Blount's epiphyseal stapling to equalise length or correct angular deformity. After an average follow up of 16.5 years, all patients with idiopathic bow-legs or knock-knees (n=12) and 71% of LLD caused by overgrowth (e.g. Klippel-Trenaunay syndrome) showed good and excellent results at skeletal maturity, whereas the results of the treatment of LLD with undergrowth of the leg and angular deformities due to trauma, infection or general dysplasia and malformation were fair to poor because of the difficulty in prediction of growth development and growth potential, allowing only for partial correction of the deformity. Besides the restriction of the stapling procedure due to the aetiology of the deformity, the age of the patients at the time of surgery is important, as it determines the complication rate of this technique (loosening or dislocation of staples). Thus Blount's epiphyseodesis should not be performed before the age of 9 years in girls and 11 years in boys. CONCLUSION: Blount's epiphyseal stapling can be recommended as a safe procedure with predictably good results in idiopathic angular deformities of the leg and leg length difference caused by overgrowth. PMID- 11760025 TI - A case of pulmonary hypoplasia associated with intrauterine brainstem necrosis. AB - An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. CONCLUSION: These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement. PMID- 11760026 TI - Honey, a palatable substance for infants: from De Rerum Natura to evidence-based medicine. PMID- 11760027 TI - A case of pseudohypoparathyroidism type la complicated with growth hormone deficiency: recovery of growth hormone secretion after vitamin D therapy. PMID- 11760028 TI - Is it possible to diagnose Rapunzel syndrome pre-operatively? PMID- 11760029 TI - Varicella zoster infection and IgG antibody formation in a 10-week-old preterm infant despite maternal immunity. PMID- 11760030 TI - Ophthalmological findings in patients with spinocerebellar ataxia type 1 are not correlated with neurological anticipation. AB - BACKGROUND: Optic atrophy, attenuation of the oscillatory potentials (OPs) of the electroretinogram (ERG), and enlargement of corneal endothelial cells, have been reported in patients with spinocerebellar ataxia type 1 (SCA1). These patients have a trinucleotide repeat expansion in the SCA1 gene and show neurological anticipation. The purpose of this study was to determine whether the ophthalmological findings are correlated with the neurological disorders, and whether ophthalmological anticipation is present in patients with SCA1. METHODS: The visual acuity, ERGs, and corneal endothelial cell density were examined in 14 patients whose DNA analysis revealed an expanded trinucleotide repeat in an allele of the SCA1 gene. The results of the tests were compared with the trinucleotide repeat number and the duration of the neuronal disease. RESULTS: The neurological disorders in the patients showed anticipation. The negative correlation between the trinucleotide repeat number and the neurological disorder was statistically significant (P<0.0001). However, the correlations between trinucleotide repeat number and visual acuity, amplitude of OPs, and corneal endothelial cell density were not significant. Statistically significant correlations were found between the duration of the neuronal disease and the visual acuity, OPs, and corneal endothelial cell density (P<0.0001, P=0.0004, and P<0.0001, respectively). The ophthalmological disorders were prominent in patients who had neuronal disease for more than 10 years. CONCLUSION: Unlike the neurological findings, the ophthalmological disorders in patients with SCA1 were not correlated with the trinucleotide repeat number of the SCA1 gene. The ophthalmological findings were most highly correlated with the duration of the neuronal disease. PMID- 11760031 TI - Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular edema associated with branch retinal vein occlusion: retinal tomography and visual outcome. AB - PURPOSE: To assess the effectiveness of surgical posterior vitreous detachment (PVD) together with gas/air tamponade in treating visual impairment from macular edema associated with branch retinal vein occlusion (BRVO-macular edema). METHODS: A cohort study was conducted. To treat visual disturbance caused by BRVO macular edema in 19 consecutive patients at a University Hospital, phacoemulsification, intraocular lens implantation, and vitrectomy were performed, together with gas/air tamponade. Patients were followed up postoperatively for 3-18 months. Foveal structure was defined using optical coherence tomography (OCT). Preoperative visual acuity, central retinal thickness, and interval between BRVO onset and operation were compared between patients with postoperative visual improvement and those without improvement. RESULTS: Ten patients recovered normal or near-normal foveal configuration, while nine patients did not. Mean postoperative visual acuity in the former group of patients was significantly higher than in the latter. Mean foveal retinal thickness decreased significantly after the operation. The interval from onset of BRVO until operation was significantly shorter in patients with improved postoperative vision than in other patients, and patients operated on within 11 months had significantly increased postoperative visual acuity. CONCLUSIONS: Surgical PVD and gas/air tamponade appears effective in treating BRVO-macular edema, although relatively short duration from disease onset until operation is critical for improvement of vision. When a good postoperative foveal contour is seen, it seems to be associated with better visual outcome. PMID- 11760032 TI - Primary vitrectomy for the management of rhegmatogenous retinal detachment associated with choroidal detachment. AB - PURPOSE: To evaluate the role and the results of primary vitrectomy in treating cases with coexisting rhegmatogenous retinal detachment and choroidal detachment. METHODS: Eleven consecutive eyes with coexisting rhegmatogenous retinal detachment and choroidal detachment with proliferative vitreoretinopathy less than grade C were included. Release of traction on the breaks was achieved by vitrectomy and augmented by episcleral buckle if needed. Perfluorocarbon liquids were used to drain the subretinal fluid through the vitrectomy sclerotomies. The breaks were treated by endolaser under perfluorocarbon liquids. Postoperative tamponade was done by C3F8 gas or silicone oil. Cases were followed up for at least 3 months. RESULTS: Retinal reattachment could be achieved and maintained in all cases by one or more surgeries. No recurrence of choroidal detachment has occurred. In each case, choroidal detachment was drained through the sclerotomies and retinal detachment was repaired. CONCLUSION: Primary vitrectomy represents an effective line in the management of rhegmatogenous retinal detachment with coexisting choroidal detachment in phakic or nonphakic eyes. SUMMARY: Primary vitrectomy is recommended for the management of choroidal detachment associated with retinal detachment. PMID- 11760033 TI - Comparison of 0.1% dexamethasone phosphate eye gel (Dexagel) and 1% prednisolone acetate eye suspension in the treatment of post-operative inflammation after cataract surgery. AB - A prospective, multi-centre, clinical parallel group study was conducted to assess the efficacy and safety of a new 0.1% dexamethasone phosphate eye gel (Group 1, n= 117) compared to 1% prednisolone acetate eye suspension (Group 2I, n=119) in a total of 236 patients (safety population), aged 39-92 years, following cataract surgery. Both drugs were given four times a day for 14 days starting 24+/-4 h after surgery. Criteria for evaluation were the reduction in anterior chamber flare and inflammation severity score (primary efficacy criteria) as well as different secondary efficacy and safety evaluation criteria. Laser photometry (LFM-500, Kowa), slit lamp assessment and the examination of other objective and subjective symptoms of ocular discomfort were performed between the last preoperative and 14th post-operative day. There were no statistically significant differences between the treatment groups concerning primary and secondary efficacy criteria. The mean reduction in anterior chamber flare from day 1 to day 14 post-operatively was 8.34+/-20.80 photons/ms with 0.1% dexamethasone eye gel and 5.72+/-16.70 photons/ms with 1% prednisolone eye suspension. The mean reduction of inflammation severity score was 1.8+/-1.3 points in Group 1 and 2.0+/-1.1 points in Group 2. Intra-ocular pressure did not increase after treatment with 0.1% dexamethasone phosphate eye gel. CONCLUSION: the results of the study underline the protective effect of topically applied 0.1% dexamethasone phosphate eye gel on the blood-aqueous barrier. This drug is an effective and safe steroidal antiinflammatory agent for topical use following cataract surgery and intraocular lens implantation. PMID- 11760034 TI - Analysis of aqueous humour proteins of eyes with and without pseudoexfoliation syndrome. AB - Pseudoexfoliation syndrome (PEX) has been suggested to represent a blood-aqueous barrier impairment leading to a higher protein content in aqueous humour of eyes with PEX. However, the nature of a prospective PEX protein has not yet been described. We set out to reevaluate protein content and examine protein composition for prospective PEX protein candidates in aqueous humour of eyes with PEX syndrome. Aqueous humour of 52 patients with PEX and 38 without PEX signs was sampled during cataract or glaucoma surgery. Total aqueous protein concentration in the samples was analysed in 43 PEX specimens and 32 non-PEX specimens according to Bradford. Aqueous protein composition of all samples was determined by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS PAGE) and silver staining. Screening for amyloids was performed in nine PEX samples and six non-PEX samples by Congo Red staining and polarised light microscopy. Aqueous protein concentration was not significantly increased in PEX eyes in comparison with non-PEX eyes. Furthermore, we could not detect any characteristic difference in protein band sizes of the two groups after SDS PAGE. However, we were able to show the presence of amyloid exclusively in aqueous humour of PEX patients. CONCLUSION: our results do not confirm a generally higher protein concentration in pseudoexfoliation syndrome eyes. This does not necessarily contradict a blood aqueous barrier impairment but illustrates the variance in protein concentration between and within the two groups. No characteristic protein band allocatable to pseudoexfoliation syndrome proteins could be detected in any of the samples. However, our findings support the theory that the pseudoexfoliation syndrome is associated with an amyloid of a serum protein. PMID- 11760035 TI - Adventitial sheathotomy for decompression of recent onset branch retinal vein occlusion. AB - Interesting results have been reported on the use of pars plana vitrectomy with adventitial sheathotomy for the decompression of branch retinal vein occlusions (BRVO). Recent onset BRVO responsible for a visual acuity of 20/40 or less have been estimated to be good candidates for this procedure. We report on the results of the prospective evaluation of three eyes (in three patients) with recent onset BRVO which underwent surgical decompression. Three men, aged 40, 50, and 68 years presenting with BRVO for 4, 4, and 3 weeks respectively, underwent surgical decompression. Initial visual acuity was 20/80, 20/80, and 20/200. After 11, 10, and 9 months follow-up, visual acuity was 20/80, 20/200, and 20/200. In two eyes, an increase of the area of retinal non-perfusion was treated with peripheral laser photocoagulation. No cataract, retinal tears or retinal detachment were observed. CONCLUSION: although feasible, sheathotomy did not lead to a significant visual improvement in our patients. Dissection of the arteriovenous crossing could have induced vascular trauma. Furthermore, vitrectomy with posterior hyaloid detachment alone could be of benefit in the treatment of branched retinal vein occlusions. A prospective randomised trial is needed to assess the effectiveness and the safety of this procedure and to determine the best candidates for surgery. PMID- 11760036 TI - Role of fas ligand in uveal melanoma-induced liver damage. AB - BACKGROUND: Uveal melanoma, the most common adult intraocular malignancy, metastasizes preferentially to the liver. Areas of cell death surrounding uveal melanoma metastases were observed in the livers of mice. We hypothesized that uveal melanoma cells might express Fas ligand (FasL), facilitating FasL-mediated apoptosis of Fas-expressing hepatocytes. PURPOSE: To determine whether Fas ligand (FasL)-expressing human uveal melanoma cells induce apoptosis of human hepatocytes in vitro and in vivo. METHODS: Human uveal melanoma cell lines were assayed for FasL expression by flow cytometry and immunohistology. A human hepatocyte cell line was assayed for Fas expression by flow cytometry. Apoptosis of hepatocytes was detected by annexin V staining in vitro, and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in vivo. RESULTS: Human uveal melanoma cell lines expressed FasL, as determined by flow cytometry and immunohistology. Human hepatocytes were Fas-positive by flow cytometry. In vitro, annexin V staining revealed that human uveal melanoma cells induced apoptosis of human hepatocytes. TUNEL staining of liver metastases revealed apoptosis of murine hepatocytes in contact with metastatic human uveal melanoma cells. CONCLUSION: FasL-induced apoptosis of hepatocytes in contact with FasL-positive human uveal melanoma cells may contribute to hepatic failure during metastatic disease. PMID- 11760037 TI - Influence of refractive correction on peripheral visual field in static perimetry. AB - PURPOSE: To determine the influence of refractive errors on peripheral visual field thresholds in automated static perimetry. METHODS: In 47 subjects (age 16 49 years), the difference of perimetric thresholds was tested in the peripheral visual field without and with contact lens correction, using a custom-made program (Goldmann stimulus size III) with the automated perimeter Octopus 2000 R. Refractive errors ranged from -16.75 to +12.5 diopters. Sixty-four test locations on three concentric rings between 30 degrees and 50 degrees in 19 hyperopic and 28 myopic eyes were tested. RESULTS: All rings in myopic eyes revealed a significant influence of refraction on the differential light sensitivity in the peripheral visual field. In hyperopic eyes only the inner ring showed a significant influence of refraction. The decrease in sensitivity, measured in dB/diopter, for the myopic inner ring was 0.75; for the myopic middle ring it was 0.46; for the myopic outer ring it was 0.22; and for the hyperopic inner ring it was 0.40. CONCLUSIONS: A significant association between refractive errors and differential light sensitivity exists in the peripheral visual field of myopic eyes. Therefore, contact lens wear is recommended when performing automated perimetry of the peripheral visual field of myopic patients with higher refractive errors. PMID- 11760038 TI - Effect of cataract surgery on intraocular pressure in eyes with previous trabeculectomy. AB - PURPOSE: To determine the course of the intraocular pressure in eyes in which cataract surgery was performed after trabeculectomy. METHODS: This was a retrospective study of consecutive patients who were scheduled for routine cataract surgery. The patients had previously undergone glaucoma filtering surgery. Pre- and postoperative data were evaluated. Both the status of glaucoma and the increase in visual acuity were monitored. RESULTS: Patients operated on over a six-year period were enrolled. The mean interval between glaucoma surgery and cataract surgery was 58.1 months. The mean duration of follow-up after cataract surgery was 31.4 months, with a minimum of 12 months. The mean central visual acuity increased by 4 lines. Before cataract surgery, 53% of the eyes had complete success (group 1), while 28% had qualified success (group 2) and the remaining 19% were failures (group 3). From group 1, 61% remained a complete success until the last visit. No eye of group 1 developed a failure. In group 2, 23% were a complete success at the final follow-up, while 4% failed. In group 3, only 35% were failures while the remaining 65% were a complete or qualified success. CONCLUSIONS: Eyes with a well-controlled intraocular pressure following trabeculectomy seem to have a favorable prognosis after subsequent cataract surgery. Eyes with qualified success or failure before cataract surgery have a slight chance of improvement in intraocular pressure control. Cataract surgery had no markedly negative effect on the intraocular pressure overall. Performing trabeculectomy and cataract surgery at different times may still be a feasible option as opposed to combined procedures. PMID- 11760039 TI - Effect of minoxidil on rabbit lens epithelial cell behavior in vitro and in situ. AB - BACKGROUND: Lens epithelial cell (LEC) proliferation and the associated production of extracellular matrix (ECM) are responsible for capsular opacification after cataract-IOL surgery. Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in procollagen hydroxylation. To evaluate the potential efficacy of minoxidil in inhibiting postoperative capsular opacification, we examined the effects of minoxidil on LEC behavior in cell and organ cultures. METHODS: We examined minoxidil effects on collagen production, migration and proliferation of cultured rabbit LECs as well as its ultrastructural effects, and also its effects on the cell population in organ cultured capsular bag. RESULTS: No cytotoxicity was identified by MTT assay at the concentrations up to 3.0 mM of minoxidil, whereas it decreased the collagen production in LECs. Minoxidil also inhibited migration and proliferation of cells. Ultrastructural observation revealed the presence of dilated endoplasmic reticulum in LECs treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors. The capsules cultured with minoxidil appeared less opaque than control specimens. On histological examination the numbers of cells on equatorial capsules were found to be significantly lower in minoxidil culture than in control culture. No lens cells were detected on the central posterior capsule of minoxidil culture, whereas they were seen in control. CONCLUSION: Minoxidil inhibited LEC migration and proliferation in vitro, as well as collagen secretion. Collagen secretion may be essential for LEC migration and proliferation. Minoxidil also attenuated repopulation of LECs on the inner surface of organ-cultured capsules. Minoxidil may be a potential inhibitor of postoperative capsular opacification. PMID- 11760040 TI - Evaluation of potential organ culture media for eye banking using a human corneal endothelial cell growth assay. AB - BACKGROUND: To evaluate the ability of different commercially available cell culture media to induce proliferation and morphological changes in primary cultures of human corneal endothelial cells (HCEC). This screening model was used in an attempt to establish a rational basis for the development of well-defined, serum-free preservation media for long-term organ culture of human donor corneas. METHODS: A total of 11 different culture media enriched with 0%, 2%, 5%, and 10% fetal calf serum (FCS) were compared. The test media were divided into three groups: Group 1: Media based on minimal essential medium (MEM), currently used for long-term corneal organ culture in European eye banks; Group 2: F99-based media, enriched for growth of corneal endothelial cells at serum-reduced conditions; and Group 3: Media designed for growth of special cell types or for short-term corneal organ culture. The growth-promoting capacity of each test medium was quantified using an HCEC proliferation assay, whereas changes in cell morphology were evaluated by phase-contrast microscopy. RESULTS: The morphological characteristics of HCEC were best maintained in the group of F99 based media, which also induced the highest level of cell proliferation under serum-reduced conditions. Specifically, the medium F99-Sr (F99 enriched with ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids) induced a two- to three-fold higher HCEC density at both 0% and 2% FCS when compared to all other test media, and it also maintained the most endothelial cell-like morphology. Also, at higher serum concentrations (5% and 10% FCS), the cell growth was most prominent in F99-Sr, as well as in the medium SFM that originally was designed for serum-free growth of vascular endothelial cells. CONCLUSION: This study suggests that the media F99-Sr and SFM should be further tested and refined as potential new storage solutions for long-term corneal organ culture at physiological temperatures. PMID- 11760041 TI - Testing of corneoscleral discs and their culture media of seropositive donors for hepatitis B and C virus genomes. AB - The prevalence of donors seropositive for hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis C virus (HCV) antibody (anti-HCV) in western countries is estimated to be 0.5%-1%. There have been only two cases, however, published so far, where hepatitis B was suspected to have been transmitted by penetrating keratoplasty [4]. Concerning HCV, no suspected transmission by keratoplasty has been reported so far. This is also true for the time before serological screening for infectious diseases became mandatory for corneal donors. In the Lions Cornea Bank North Rhine Westfalia, 4.7% (HBV) and 3.2% (HCV) respectively of the corneas of the years 1995 to 1999 were discarded due to a "non-negative serology". In about 50% of these cases the screening test (ELISA) generated no valid signal and, therefore, a "questionable positivity" was assumed. Since in Germany corneal graft shortage still is a limiting factor for penetrating keratoplasty, this study was to evaluate the detectability of HBV-DNA and HCV-RNA in the serum samples, organ culture media and corneas of donors tested seropositive for HBsAg or anti-HCV in an attempt to obtain information as to the potential infectivity of this donor material. In this study, 29 corneas of 17 donors seropositive by ELISA for HBsAg and 27 corneas of 14 donors seropositive by ELISA for anti-HCV were evaluated. The organ culture media and the sera were screened for the presence of HBV-DNA or HCV-RNA by PCR. The corneoscleral discs were divided into a central trephinate (7 mm) and the corneoscleral rim. Concerning HBV-DNA both tissues were examined separately by polymerase chain reaction (PCR). In the case of HCV-RNA, a further, more sensitive nucleotide amplification method (NAT), the transcription mediated amplification (TMA), was used to test media, central corneas and cornealscleral rims. The media were additionally tested by PCR. Viral nucleic acid was detected in the sera from 6 of 17 HBsAg positive donors and from 6 of 14 anti-HCV positive donors. Viral genomes could not be detected in the organ culture media nor in the central corneas or corneoscleral rims by PCR at a detection limit of 1000 and 100 copies/ml. Concerning HCV-RNA, two media were positive in the TMA with 50-100 copies/ml. CONCLUSION: according to our results, the risk of transmitting hepatitis B or C virus by penetrating keratoplasty appears to be low: although hepatitis C virus RNA could be detected in 2 media (from two donors) out of 27 with a low concentration of virus copies between 50 100/ml. It remains open whether such a low virus particle number may cause infection in the recipient. PMID- 11760042 TI - Morphological and functional changes due to drug-induced lysosomal storage of sulphated glycosaminoglycans in the rat retina. AB - A series of dicationic amphiphilic drugs, most of them immunomodulatory agents, are known to induce generalised lysosomal storage of sulphated glycosaminoglycans (GAGs) in rats and in cultured cells of several species including man. The present study deals with the cytological effects of two experimental immunomodulatory acridine derivatives upon the retina of rats. The animals were treated orally with compound CL-90.100 (3,6-bis[2-(diethylamino)ethoxy]acridine) or an analogue for periods up to 22 weeks at a dose range of 60-90 mg/kg body weight and the retinae examined by light and electron microcopy. ERG measurements were done initially and after 16 weeks of treatment. All types of retinal cells developed abnormal cytoplasmic vacuoles which represented the ultrastructural counterpart of lysosomal GAG storage as demonstrated by histochemical and cytochemical staining experiments. The retinal pigment epithelium and the Muller cells were most prominently affected, photoreceptor cells to a lesser degree, and retinal neurons to varying degrees. The topographical distribution of the drug as detected by fluorescence microscopy closely resembled the distribution of the GAG accumulation in the retinal layers. After treatment for 16 weeks, the a-and b wave amplitudes in the ERG were significantly reduced compared with the controls. CONCLUSION: the glycosaminoglycan storage in pigment epithelium is reminiscent of that seen in some inherited mucopolysaccharidoses of humans. When a given cell type shows lysosomal accumulation of glycosaminoglycans as a consequence of impaired degradation, it can be assumed to be engaged in the turnover of glycosaminoglycans under normal conditions. Thus the present results suggest that not only the retinal pigment epithelium but also Muller cells, photoreceptor cells, and, to variable degree, retinal neurons are normally involved in the catabolism of sulphated glycosaminoglycans. We believe that the lysosomal storage of glycosaminoglycans caused secondary cellular disturbance responsible for the functional changes shown by electroretinography. PMID- 11760043 TI - Exposure to a solar eclipse causes neuronal death in the retina. AB - BACKGROUND: A solar eclipse was observed in Europe on 11 August 1999. Several individuals suffered from transient or persisting retinal damage, caused by gazing at the eclipse without adequate eye protection. Retinal damage is the most serious hazard of exposure to light. but the mechanisms by which this type of exposure produces retinal damage and its cellular correlates are not yet established. We used an animal model to monitor the mechanisms of retinal damage following excessive light exposure, and in particular to study whether observation of the eclipse induces death of retinal cells. METHODS: In the geographic area where the experiment was conducted, a partial (90%) solar eclipse was observed. Experimental albino rats were exposed to these eclipse conditions, and control rats were exposed to normal sunlight. Another group of control animals was exposed to the same conditions, but was provided with protective light filters of the type recommended for human use. The DNA fragmentation in retinal sections of the various groups was analysed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. This analysis revealed that exposure to both normal sunlight and to the eclipse resulted in neuronal apoptosis. Immunohistochemical techniques were used to evaluate possible glial vascular alterations. RESULTS: Dying cells could first be detected 24 h after exposure, the largest number of which were found 6 days later in the photoreceptor layer. Control levels were attained 14 days after the exposure. Retinal ganglion cells underwent apoptosis in both groups (normal sunlight and eclipse exposure), whereas in the neuroglial cells there was an up-regulation of the intermediate filament content. The number of dying cells in both groups was greater in animals whose pupils had been dilated pharmacologically during exposure. On the other hand, the protective filters were effective in preserving the rat retinal cells from apoptosis. CONCLUSIONS: These results show, for the first time, that the cellular correlates of solar retinopathy are neuronal apoptosis accompanied by glio-vascular responses. Cellular apoptosis is an irreversible process, which could manifest itself as permanent visual impairment. The activation of non-neuronal cells, such as glial and endothelial cells, could be responsible for the more transient clinical symptoms. PMID- 11760044 TI - Use of a serum-free medium for long-term storage of human corneas. Influence on endothelial cell density and corneal metabolism. AB - BACKGROUND: The success of long-term corneal organ culture is limited by the progressive loss of endothelial cells during culture and the use of culture medium supplemented with fetal calf serum as a possible source of contamination with infectious agents. In this study, we investigated the suitability of a serum free medium (Endothelial-SFM) to improve preservation conditions for human donor corneas. METHODS: Six pairs of corneas were stored in Minimum Essential Medium (MEM) supplemented with 2% fetal calf serum (FCS) for 8-14 days. One cornea of each pair was then further cultivated in Endothelial-SFM supplemented with 2% FCS or in MEM with 2% FCS, respectively. In a second series of experiments, the endothelial cell density of seven pairs of freshly isolated donor corneas was determined during cultivation in Endothelial-SFM with 2% FCS or serum-free Endothelial-SFM. RESULTS: After precultivation in conventional medium, the endothelial cell density of corneas allocated to cultivation in Endothelial-SFM was 1000-1950 cells/mm2 and that of those subsequently cultured in MEM 1200-2000 cells/mm2. At 9 weeks, cell densities of 900-1500 cells/mm2 were found after cultivation in Endothelial-SFM compared with a total cell loss in MEM. Freshly isolated corneas cultured in Endothelial-SFM with or without FCS supplementation showed a decrease of endothelial cell density of about 20% within the first 2 weeks of storage. During further cultivation cell density remained constant without statistically significant differences between the groups. Glucose consumption of the corneas was higher in Endothelial-SFM than in MEM. Corneas stored in Endothelial-SFM with 2% FCS showed a higher glucose consumption than those preserved in serum-free Endothelial-SFM. CONCLUSION: Organ culture of human donor corneas using the serum-free basal medium Endothelial-SFM is superior to conventional culture conditions because the decrease in endothelial cell density can be ameliorated, the culture period can be prolonged and the risk of transmitting infectious agents via serum can be minimised. PMID- 11760045 TI - Multidisciplinary graduate education in analytical chemistry. PMID- 11760046 TI - Ultra-trace analytical monitoring of silicon wafer surfaces by capillary electrophoresis. AB - Several methods are presented for the routine ultra-trace analytical monitoring of inorganic and organic anions and cations on the surface and in the native oxide of silicon wafers--the wafer-surface water-extraction method, the vapor phase-decomposition method, and the re-dissolving method. Electrokinetic injection, sample stacking, and electrolyte composition were, therefore, optimized and made robust. For electrokinetic injection with transient isotachophoretic preconcentration a linear range of 0.05 to 0.5 micromol L(-1) was obtained; for sample stacking the linear range was 0.5 to 10 micromol L(-1), even in the presence of up to 750 micromol L(-1) hydrofluoric acid. Inorganic anions and monovalent carboxylic acids are predominately dissolved in the aqueous layer on the wafer surface whereas dicarboxylic acids are chemically bonded to the silanol groups and form esters. PMID- 11760047 TI - Effect of additives on the flow-analysis determination of weak-acid-dissociable and total cyanide. AB - The effect of reductants, complexants, and nitrite eliminators on the flow analysis determination of weak-acid-dissociable and total cyanide has been studied for: 1. cyanide recovery from copper, nickel, and iron complexes; 2. cyanide generation from the reagents in the presence of common interferents; and 3. cyanide consumption by the reagents in the presence of those interferents. In the absence of additives the UV-assisted recovery of (total) cyanide from the iron complexes (using a succinate buffer) was insufficient. Arsenite and hypophosphite had no measurable effect on the recovery, ascorbic acid resulted in total recovery but under these conditions nitrite and sulfite seemed to destroy cyanide. Phenanthroline promoted the recovery of cyanide from iron complexes but led to formation of cyanide from thiocyanate. Citrate resulted in good recovery but in the presence of nitrite cyanide was formed; the recovery with EDTA was also good. It proved necessary to destroy nitrite by use of sulfamic acid. If a combination of EDTA, citrate, and sulfamic acid is used rather high concentrations of thiocyanate, nitrite, thiosulfate, and sulfite can be tolerated in the samples. It is strongly advisable to test modifications of the cyanide determination comprehensively, because some surprising results have been obtained. PMID- 11760048 TI - Comparative study of the determination of peroxomonosulfate, in the presence of other oxidants, by capillary zone electrophoresis, ion chromatography, and photometry. AB - Several methods for quantitative determination of peroxomonosulfate in detergents, in the presence of other oxidants, have been investigated. The photometric technique applied was based on the well-known starch-iodine reaction. The oxidizing agent was quantified by determining the amount of iodine produced. The influence of other oxidants present was examined. Ion analysis was performed by capillary zone electrophoresis (CZE) and ion chromatography (IC). Because peroxomonosulfate in detergents is always accompanied by sulfate, the main goal was to separate the sulfur species without causing the decomposition of the unstable peroxomonosulfate ion. The sulfur species could be separated within less than 4 min by CZE with a pyromellitic acid electrolyte at pH 3.5 to 5.0. Sulfate and peroxomonosulfate were separated by IC within 11 min by use of a phthalic acid mobile phase at pH 3.0. The peroxomonosulfate content was determined by calibration. The calibration plot was linear from 5 to 50 microg mL(-1) SO5(2-) for IC and from 7.3 to 182.3 microg mL(-1) SO5(2-) (corresponding to 20 to 500 microg mL(-1) triple salt) for CZE. PMID- 11760049 TI - Hyphenation of gas-diffusion separation and ion chromatography. Part 1: determination of free sulfite in wines. AB - The hyphenation of gas-diffusion separation and ion chromatography (IC) is described as a convenient, reliable, robust, and economic method for in-line sample pre-treatment. The high selectivity associated with this method permits direct analysis of samples containing microparticulates, colloidal matter, and/or high molecular weight compounds. The determination of sulfite serves as a first example of its application. The method is based on the diffusional separation of SO2 following in-line oxidation with hydrogen peroxide to sulfate and final determination of the sulfate formed using IC. The influence of operational parameters has been thoroughly investigated and gas-diffusion cells of different geometries compared with respect to the gas-transfer rates obtained. Application to the analysis of wines demonstrates the utility of the method. PMID- 11760050 TI - Determination of iodide in urine by ion-pair chromatography with electrochemical detection. AB - A variety of parameters affecting the determination of iodide in biological materials by ion-pair chromatography and electrochemical detection were examined in detail. It became apparent that the pH value, the ion-pair concentration, the proportion of organic solvent and of organic bases as a component of the buffer solution, as well as the salt concentration in the eluent system could effectively influence the retention characteristics of iodide in the chromatographic system, resulting in the separation of potential interfering substances. The presence of other anions in the sample matrix has to be taken into consideration, particularly thiocyanate because of its long retention time. Investigations of the electrochemical detection mechanism revealed that the reaction hitherto assumed to be responsible for detector signal generation (formation of AgI) is incorrect. In addition, a much more sensitive detection of iodide than that cited in the literature to date is possible if the detector potential is optimally selected and any anticipated interfering substances are removed by chromatography. Use of a gold electrode rather than a silver electrode also considerably enhances the reliability of the procedure. PMID- 11760051 TI - Review of analytical methods for the determination of estrogens and progestogens in waste waters. AB - Steroid sex hormones and related synthetic compounds, e.g. those used in contraceptive pills, have been shown to be present in the aquatic environment, mainly as a result of inefficient removal in waste-water-treatment plants (WWTP). The concentrations of the compounds, although very low (low ng L(-1)), are sufficient to induce estrogenic responses and alter the normal reproduction and development of wildlife organisms. The compounds have been determined, by a variety of analytical procedures, in the influents and effluents of WWTP, within research programs conducted in different countries to evaluate the efficiency of the waste-water-treatment processes currently in use. Determination of natural and synthetic estrogens and progestogens in waste water is, however, a difficult analytical task, because the very low detection limits required and the complexity of the waste-water matrix necessitate the execution of a considerable number of steps. Thus, in general, complicated, time-consuming extraction and purification processes, usually based on the application of solid-liquid extraction, are performed before final determination by immunoassay, high performance liquid chromatography, or, most often, gas chromatography coupled with mass spectrometry. This paper reviews the analytical methods so far described for the analysis of these important environmental pollutants in waste water and discusses the key procedural steps, from sampling to analysis, and the techniques most commonly used in the determination. PMID- 11760053 TI - Antibody-based methods for surfactant screening. AB - This brief overview summarises the immunoassay-based results obtained in the course of two years of the European INCO-Copernicus project BIOTOOLS. The project is aimed at simplifying the procedures for detection of surface active compounds (SAC) using, among others, antibody-based methods, i.e., microtiter plate-based enzyme-linked immunosorbent assays (ELISA), polarisation fluoro immunoassays (PFIA), and enzyme flow injection immunoassays (FIIA). Thirty-three rabbits were immunised with five different sulphophenyl moieties and three p-hydroxyphenyl moieties conjugated to protein immunogens to produce analytical antibodies against linear alkylbenzene sulphonates (LAS) and nonylphenol (NP). Although most of the antibodies exhibited binding reaction in indirect ELISA, only a few showed the required assay sensitivity. The best antibodies for LAS exhibited a 50% binding inhibition at IC50 19.8 microg L(-1) in indirect ELISA. Similar inhibition was observed for direct ELISA using peroxidase tracers. Antibodies against NP allowed the establishment of an indirect assay operating in the mg L( 1) range. A rapid and simple protocol for the screening of NP and LAS using homogeneous PFIA is described. The assay time for 10 samples was 7 minutes, thus allowing fast detection of the selected SAC at the mg L(-1) level. A generic competitive FIIA system, using a protein G column for separation of free and antibody-bound beta-galactosidase (beta-Gal) tracer, was developed for the screening of LAS, NP, and nonylphenol decaethoxylate (NPEO10). The FIIA had a sample throughput (STP) of 5-10 samples per hour, with limits of detection (LOD) for LAS, NP, and NPEO10 of 19.5, 52, and 2.4 microg L(-1), respectively. The developed FIIAs were applied to spiked rain and surface water. PMID- 11760052 TI - LC-MS determination of linear alkylbenzene sulfonates and their carboxylic degradation products in influent and effluent water samples and sludges from sewage-treatment plants. AB - Linear alkylbenzene sulfonates (LAS) have been determined in samples of the influent and the effluent, and in the sludge, from sewage-treatment plants (STP). LAS and sulfophenyl carboxylate compounds (SPC) were isolated by solid-phase extraction (SPE) with the polymeric phase Isolute ENV, then determined by liquid chromatography-electrospray mass spectrometry (LC-ESI-MS). The method enabled unequivocal identification of C10-C13 LAS by monitoring the ion at m/z 183 and the base peak corresponding to the [M-H]- ion. Average recoveries varied from 77 93% and the linear range of the method varied from 0.2 to 10 microg L(-1), with a limit of detection ranging from 10 ng L(-1) to 1.5 microg L(-1) when 200 mL waste water were preconcentrated. For sewage sludge, recoveries varied from 58 to 90% and the linear range was between 0.2 and 100 microg L(-1), with a detection limit ranging from 0.4 to 120 microg kg(-1) when 2.5 g sewage sludge was extracted. Unequivocal identification and determination of some metabolites of the LAS, the sulfophenyl carboxylate compounds (SPC), was achieved by monitoring [M-H]- ions. PMID- 11760054 TI - Characterization of wastewater toxicity by means of a whole-cell bacterial biosensor, using Pseudomonas putida, in conjunction with chemical analysis. AB - A new amperometric biosensor based on inhibition of Pseudomonas putida has been developed to assess the acute toxicity of wastewater. This system uses the biological component immobilized on disposable screen-printed electrodes. The responses for a selected group of polar organic standard substances were studied using Pseudomonas putida as biological component. The results have been compared with responses obtained using the same system and Escherichia coli as biological component and with the bioluminescence inhibition of Vibrio fisheri using ToxAlert 100. Different properties, e.g. the standard deviation (SD) of the data, the goodness of fit (R2) and the standard deviation (Syx) of the vertical distances of the points from the inhibition curve, the 50% effective concentration (EC50) and the toxicity units (TII50) of the standard substance, were calculated and compared. This biosensor was used to assess the acute toxicity of real wastewater samples collected at different wastewater treatment plants (WWTP). Finally, a sequential solid-phase extraction (SSPE) procedure followed by liquid chromatography-mass spectrometry (LC-MS) was used to determine the polar organic toxic substances present in the wastewater samples. PMID- 11760055 TI - Marine microalgae toxicity test for linear alkylbenzene sulfonate (LAS) and alkylphenol ethoxylate (APEO). AB - Different microalgal species have been used in growth-inhibition tests to determine the toxic concentrations of anionic and non-ionic surfactants to phytoplankton. The species used were selected from different taxonomic groups, all of considerable ecological relevance to marine environments. The toxicity of the C13 LAS homologue to the microalgal species selected was usually one order of magnitude greater than that of the C11 homologue. The toxicity of a commercial LAS mixture to different microalgal species was also checked. For this material and C. gracilis, cellular counting by means of a Neubauer chamber and by use of a flow cytometer were compared; differences between the two methods were insignificant. The toxicity of decaethoxylated nonylphenol non-ionic surfactant to C. gracilis was also checked; the EC50 value for this compound was 1.0 mg L( 1). PMID- 11760057 TI - Bioconcentration of linear alkylbenzene sulfonates and their degradation intermediates in marine algae. AB - Sorption experiments using different homologues of linear alkylbenzene sulfonate (LAS) and sulfophenylcarboxylic acid (SPC) on several marine microalgae have been carried out. The steady state seems to be reached in the first 4 hours. Longer exposure times lead to biodegradation of the compound and, therefore, to an overestimation of the bioconcentration factor. Sorption coefficients are higher for Nannochloropsis gaditana, for example, 1,293 Lkg(-1) for C11-LAS and 525 Lkg( 1) for C11-SPC versus 727 Lkg(-1) for C11-LAS and 28 Lkg(-1) for C11-SPC for Dunaliella salina. For both algae an increase in the sorption coefficient is observed when the polarity of the compound decreases (C5-SPC3) and LAS homologs in marine samples by a simple, sensitive, and specific method giving high recoveries and reproducibility. SPC with from three to twelve carbon atoms in the carboxyl chain have been found in marine water samples. PMID- 11760058 TI - Use of an automated on-line SPE-HPLC method to monitor caffeine and selected aniline and phenol compounds in aquatic systems of Macedonia-Thrace, Greece. AB - Caffeine and selected aniline and phenol compounds have been monitored in the river, lake, and ground water of Northern Greece (Macedonia-Thrace) from September 1999 to December 2000 by means of a fully automated on-line SPE-HPLC method. Among the target aniline and phenol compounds the most abundant was 2,6 di-tert-butyl-4-methylphenol, which was found to be present in both surface and ground water samples. Caffeine was also very frequently present in river and ground water, although its presence in lake water was rare. Caffeine and 2,6-di tert-butyl-4-methylphenol were also monitored by off-line SPE of water samples and GC-ion-trap MS analysis of extracts. PMID- 11760059 TI - In-situ separation of the matrix for the direct determination of traces of chromium, cobalt, and nickel in titanium dioxide powder by electrothermal atomic absorption spectrometry with slurry sampling. AB - A novel method has been developed for the direct determination of traces of chromium, cobalt, and nickel in TiO2 powder; it entails slurry sampling and electrothermal atomic-absorption spectrometry (ETAAS) with a polytetrafluoroethylene (PTFE) slurry (6% m/v) as fluorinating reagent. The factors which could affect the vaporization of the matrix and analytes were studied in detail; the fluorinating vaporization behavior of the analyte both in the slurry and in solution were also investigated. Owing to the in-situ separation of the matrix, the matrix influences were reduced significantly. The proposed method has been applied to the direct determination of traces of chromium, cobalt, and nickel in high-purity TiO2 powder without chemical pretreatment. Under the optimum experimental conditions the detection limits of the analytes (Cr, Co, and Ni) were 1.9 ng g(-1), 2.4 ng g(-1) and 5.4 ng g(-1), respectively, the relative standard deviations (RSD) were 3.4% (n=6, c=7.0 ng mL( 1)), 2.9% (n=6, c=0.70 ng mL(-1)), and 7.6% (n=6, c=4.0 ng mL(-1)), again respectively, and the characteristic masses for Cr, Co, and Ni were 8.4 pg/ 0.0044A, 9.3 pg/0.0044A, and 40.0 pg/0.0044A, respectively. PMID- 11760060 TI - Modification of the electroosmotic flow and separation selectivity of anions in electrochromatography with pseudo-stationary phases of C14 alkyldimethylammoniopropane sulfonate zwitterionic surfactants by addition of salts to the background electrolyte. AB - The effects of salts (NaCl, NaClO4, MgCl2, CeCl3) added to background electrolyte (BGE) solutions (10 mmol L(-1) sodium phosphate, pH 7.2) on electroosmotic flow (EOF) and the separation selectivity of anions (chloride, bromide, iodide, nitrite, nitrate, chlorate, thiocyanate, iodate, chromate, and molybdate ion) by capillary electrochromatography using the zwitterionic surfactant 3-(N,N dimethylmyristylammonio)propane sulfonate (C14N3S) as a pseudo-stationary phase were investigated. There are two mechanisms affecting the separations: 1. the cations and anions of the added salts interact with the zwitterionic surfactant to varying degrees, thus changing the overall retention of the analytes; and 2. they change the EOF and the resulting apparent mobilities. It was shown that a BGE containing perchlorate and a low concentration of zwitterionic surfactant (2 mmol L(-1)) gave a stable and reproducible EOF and the concentration of perchlorate could be used to manipulate the separation selectivity for polarizable anions, such as iodide and thiocyanate. These effects are discussed in terms of measured association constants describing the interaction of anions and cations with the zwitterion. PMID- 11760061 TI - Ruthenium and ruthenium dioxide-modified graphite-ethylene/ propylene/diene and graphite-teflon composite electrodes as amperometric flow detectors. Application to the determination of methionine. AB - The flow injection amperometric performance of solid composite graphite electrodes with ethylene/propylene/diene (EPD) or Teflon as binding agents, and with Ru or RuO2 particles as electrocatalytic modifiers has been compared. Both, Ru and RuO2 modified electrodes exhibited electrocatalytic properties on the methionine oxidation process in alkaline media. The electrodes composition and the hydrodynamic and chemical variables were optimized. Graphite-EPD (GEPD) electrodes showed a better analytical performance than graphite-Teflon (GPTFE) electrodes. Furthermore, a better sensitivity, repeatability and reproducibility was observed for RuO2-GEPD electrodes when compared with Ru-GEPD electrodes. At an applied potential of +0.50 V, a detection limit for methionine of 4.8x10(-5) mol L(-1), similar to those reported in the literature for other RuO2-modified electrodes, was obtained. The analytical applicability of RuO2-GEPD electrodes was demonstrated by determining methionine in a complex pharmaceutical formulation. PMID- 11760062 TI - Development of a personal isocyanate sampler based on DBA derivatization on solid phase microextraction fibers. AB - The design and evaluation of a portable diffusive sampler for isocyanates is described. The sampler employs dibutylamine (DBA) loaded onto 60-microm polydimethylsiloxane-divinylbenzene (PDMS-DVB) solid-phase microextraction (SPME) fibers. The DBA-isocyanate derivative is then desorbed by sonication and analyzed by LC-MS using atmospheric pressure chemical ionization (APCI). The samplers are calibrated (i.e. the uptake rate is calculated) by exposing them to a known concentration of hexamethylene diisocyanate (HDI) in a standard gas-generation chamber. The uptake rate for the proposed method, at room temperature (25 degrees C), is 1.13 pg (min ppb(v))(-1) and the method detection limit is 3.2 microg m( 3), equivalent to less than 10% of the airborne time-weighted average (TWA) exposure limits recommended by both the National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH). Practical points that should be considered when using the SPME device as a diffusive sampler are discussed. PMID- 11760063 TI - Sensitive method for determination of methyl tert-butyl ether (MTBE) in water by use of headspace-SPME/GC-MS. AB - A simple and rapid method for the determination of methyl tert-butyl ether (MTBE) in water by headspace-solid-phase microextraction (headspace-SPME) at sub microg/L concentrations is described. On using a cooled SPME fiber coated with a 75-microm layer of poly(dimethylsiloxane)/carboxene and heating the sample to 35 degrees C, about 4 times more MTBE is extracted compared to SPME extraction with the fiber placed in the water sample. Stable analytical conditions with a detection limit of 10 ng/L are achieved. By use of a sample volume of 4 mL in a 10 mL vial, a sodium chloride content of 10% (w/w), and an extraction time of 30 min, the total time of an analytical cycle was optimized to 39 min. Precise linearity of R2>0.9991 and R2>0.9916 in the calibration range of 20-5000 ng/L and 20-100 ng/L, both in addition to blanks, respectively, and relative standard deviations of 10% (100 ng/L, long-term) and 11% (20 ng/L, short-term) are presented. The recovery is well within the accepted limits of 83-118% at a concentration of 100 ng/L and even close thereto at trace levels of 20 ng/L (96 125%). The data presented for a concentration of 100 ng/L are examined by statistical methods and show results for the T test at the 95% confidence level. Due to the large concentration range covered, the method is well suited for the monitoring of MTBE in the aquatic environment. PMID- 11760065 TI - Quantitative analysis of active compounds in pharmaceutical preparations by use of attenuated total-reflection Fourier transform mid-infrared spectrophotometry and the internal standard method. AB - A new method is presented for the quantitative analysis of compounds in pharmaceutical preparations Fourier transform (FT) mid-infrared (MIR) spectroscopy with an attenuated total reflection (ATR) module. Reduction of the quantity of overlapping absorption bands, by interaction of the compound of interest with an appropriate solvent, and the employment of an internal standard (IS), makes MIR suitable for quantitative analysis. Vigabatrin, as active compound in vigabatrin 100-mg capsules, was used as a model compound for the development of the method. Vigabatrin was extracted from the capsule content with water after addition of a sodium thiosulfate IS solution. The extract was concentrated by volume reduction and applied to the FTMIR-ATR module. Concentrations of unknown samples were calculated from the ratio of the vigabatrin band area (1321-1610 cm(-1)) and the IS band area (883-1215 cm(-1)) using a calibration standard. The ratio of the area of the vigabatrin peak to that of the IS was linear with the concentration in the range of interest (90-110 mg, in twofold; n=2). The accuracy of the method in this range was 99.7-100.5% (n=5) with a variability of 0.4-1.3% (n=5). The comparison of the presented method with an HPLC assay showed similar results; the analysis of five vigabatrin 100-mg capsules resulted in a mean concentration of 102 mg with a variation of 2% with both methods. PMID- 11760064 TI - Cloud-point preconcentration and HPLC determination of polycyclic aromatic hydrocarbons in marine sediments. AB - Cloud-point methodology has been used to develop a new procedure for preconcentration of polycyclic aromatic hydrocarbons previously extracted from marine sediment with a micellar polyoxyethylene-10-lauryl ether medium by microwave- or ultrasound-assisted extraction. The optimum conditions for preconcentration and determination of PAH by HPLC with UV detection were established. The optimized procedure was applied to determination of these analytes in fortified marine sediment. The mean recoveries obtained after extraction and preconcentration by use of microwave- or ultrasound-assisted extraction were 105.8 and 99.5%, respectively. Precision, however, is considerably higher when extraction is performed ultrasonically. PMID- 11760066 TI - An attempt to correlate fat and protein content of biological samples with residual carbon after microwave-assisted digestion. AB - The residual carbon content of a variety of bovine-derived samples and forage was determined by inductively coupled plasma optical emission spectrometry with radial view configuration (ICP-OES) after microwave-assisted digestion under high pressure in a closed vessel. The original carbon concentration in the samples was determined by elemental analysis. The highest amount of original carbon content (64%) was found in viscera. After digestion, up to 75% of it was destroyed. Viscera presented the highest ether extract and blood exhibited a high crude protein content of up to 99%. The efficiency in destroying the organic matter in biological materials seemed to be related to their fat content and showed no significant difficulty for protein-rich samples. The correlation coefficient between the fat content of the samples and the residual carbon after acid decomposition was 0.9173 indicating a fair fit. However, no correlation was observed between % RC and the protein content. PMID- 11760067 TI - Process control of apple winemaking by low-resolution gas-phase Fourier-transform infrared spectroscopy. AB - Four apple wine fermentation processes have been observed by means of direct inlet gas-phase FTIR spectroscopy. The apple juice concentrates were each fermented by two species of Saccharomyces cerevisiae starters, and the experiment was repeated. The development of the concentrations of 1-propanol, 4 methylpyridine, acetaldehyde, acetic acid, and ethyl acetate was monitored. Two different sampling methods were used--static headspace and direct injection of the must. The performance of the FTIR method is limited by the high ethanol concentration. It can be mathematically proven that the amount of sample can be selected so that any distortion due to ethanol is minimized. Headspace GC-MS was used for preliminary compound identification. PMID- 11760068 TI - How to overcome matrix effects in the determination of pesticides in fruit by HPLC-ESI-MS-MS. AB - A high-performance liquid chromatographic method, with electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS-MS) for detection, has been developed for the determination of thiabendazole, carbendazime, and phenylurea pesticides in fruit matrices. During the validation process the method was tested for matrix effects, blanks, and the stability of the system. Considerable unspecific matrix effects in the ESI (+) process were detected by comparing standard calibration, and matrix calibration, although blank values were very low and the specific calibration functions showed only small standard deviations. This effect was overcome by using a more complex clean-up, i.e. an additional size-exclusion step. PMID- 11760069 TI - Direct determination of traces of beryllium with eriochrome cyanine R by diffuse reflection spectroscopy using chromaticity functions. AB - Chromaton-N-super and Silasorb C18 (SMT C18) were compared as solid supports for the direct determination of the immobilized beryllium complexes with eriochrome cyanine R by diffuse reflection spectroscopy. The advantage of Silasorb C18 was shown. A detection limit of 0.0002 microg mL(-1) could be reached in a 100-mL sample. The method was used for the analysis of real water samples. PMID- 11760070 TI - Determination of niobium in pyrochlore ore by differential pulse polarography. AB - A differential pulse polarographic method has been developed for the quantitative determination of niobium in pyrochlore ore. One-step polarographic curves were obtained in 0.01 mol L(-1) EDTA as supporting electrolyte. Analytical curves indicated that response was linearly dependent on Nb(V) concentration between 1.6 and 8.6 mg L(-1) in the pH range 2-5. The system is quasi-reversible and controlled by diffusion in 0.01 mol L(-1) EDTA as supporting electrolyte; the electrode process involves one-electron reduction of Nb(V) to Nb(IV). The results obtained so far for niobium in pyrochlore ore were comparable with those obtained by X-ray fluorescence determination. Ions such as Fe(III), Cr(III), As(III), Cu(II), Ni(II), Co(II), Mn(II), Sn(IV), Zn(II), V(V), Ta(V), W(VI), Ce(IV), and Ti(IV) did not interfere. Possible interference from Pb(II) can be avoided by complexation with the supporting electrolyte in the pH range 3.5 to 4.6; Mo(VI) ions can be tolerated when their concentration is one-tenth that of Nb(V). PMID- 11760071 TI - Voltammetric determination of iodide by use of an interdigitated microelectrode array. AB - An interdigitated microelectrode array (IDA) sensor has been applied to the determination of iodide in mineral water. It is based on reversible charge transfer in the redox system I2/2I- at a platinum microelectrode. The analytical signal from the IDA system was obtained by use of a bipotentiostat in dual mode. One segment of the IDA (generator) was polarized to the limiting current for oxidation of iodide to iodine in 0.1 mol L(-1) HClO4. The second segment (collector) was fixed at a potential value corresponding to the limiting current of iodine reduction. The geometrical arrangement of the IDA enables this transfer with high efficiency. Because the diffusion layer of both segments overlaps the iodide produced on the collector, the iodide diffuses back to the generator where it is reoxidized. Therefore, redox cycling will enhance the voltammetric signal of the IDA. The signal obtained with a vertically separated IDA was 20 times higher than that in the single mode. Because multiplication of the signal reduces the detection and determination limits, direct voltammetric determination of iodide in mineral water is possible. PMID- 11760072 TI - Organic contaminants in water--conceptual considerations for the production of liquid reference materials in support of the new water framework directive. AB - The lack of suitable certified reference materials for the determination of organic pollutants in water has become a major problem within the framework of the new European water policy. This paper highlights approaches towards the production of certified reference materials and their drawbacks. On the basis of experience gained from proficiency-testing schemes, analytical practice, and reference material production a new concept for the production of liquid reference materials to be used in support of European legislation is presented and discussed briefly. The concept is based on a standard-addition approach and the simulation of effects interfering with the analytical process by use of individual matrix constituents or matrix-mimicking substances in combination with water-miscible solvents. The concept enables quantification of dissolved organic compounds in unknown water samples and evaluation of the analytical process with the help of a reconstituted sample. Open questions for further research are also outlined. PMID- 11760073 TI - A novel water-soluble fluorescent probe for the determination of methylamine. AB - A novel water-soluble fluorescent probe, monosodium 7-(4,6-dichloro-1,3,5 triazinylamino)-1,3-naphthalenedisulfonic acid (DTND), was synthesized by reacting cyanuric chloride with 7-amino-1,3-naphthalenedisulfonic acid monopotassium salt at 0-5 degrees C. This new reagent was used for the determination of methylamine. The linear range is 3x10(-6)-2x10(-4) mol L(-1) with a detection limit (S/N=3) of 7.2x10(-8) mol L(-1), and the relative S.D. is 1.3% for ten replicate determinations of 1x10(-5) mol L(-1) CH3NH2. Common species in the aqueous environment have no or only slight influence on the determination. The method can be used to determine methylamine in real water samples. PMID- 11760074 TI - Detection of BSE-risk materials. PMID- 11760075 TI - Meeting report of the 73rd Japanese gastric cancer congress. PMID- 11760076 TI - Molecular diagnosis of gastric cancer: present and future. AB - Although histopathological diagnosis is extremely useful for the definitive as well as the supportive diagnosis of gastric cancer in clinical practice, it is limited in certain respects. Over the past 15 years, integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. These abnormalities, which include telomerase activation, genetic instability, and abnormalities in oncogenes, tumor suppressor genes, cell-cycle regulators, cell adhesion molecules, and DNA repair genes, could be effective markers in the molecular diagnosis of gastric cancer. It is possible that the molecular analysis of these alterations in histopathology specimens may overcome deficiencies in diagnoses that depend only on histomorphology, and, consequently, we may be able to improve the differential diagnosis of cancer, obtain information on the grade of malignancy, and identify patients at high risk of developing multiple primary cancers. In Hiroshima, we have established a system of molecular-pathological diagnosis as a routine service; about 5,000 lesions of the stomach have been subjected to this diagnosis, and much useful information has been obtained. In the near future, genetic analysis by means of DNA microarray may become routine in the diagnosis of gastric cancer. Genetic analysis of histopathology specimens may make clear the characteristics of individual cancers; indicating the common and specific features of molecular pathogenesis that may be directly connected with gene therapy or molecular-targeted therapy. By analyzing the relationship between single-nucleotide polymorphisms and cancer susceptibility, we will be able to obtain information on cancer prevention from histopathology samples. PMID- 11760078 TI - Effect of periodic endoscopy for gastric cancer on early detection and improvement of survival. AB - BACKGROUND: Increases in the detection of early gastric cancer have indisputably, improved long-term survival. The aim of this study was to establish the value of periodic gastric endoscopy and the appropriate intervals for its performance. METHODS: We compared, retrospectively, the clinicopathologic characteristics and outcomes of two groups of patients who had undergone surgical treatment for gastric cancer. Of a total of 361 patients, 106 had undergone endoscopic examination within 2 years before the detection of gastric cancer (group 1), and 255 had either undergone no endoscopic examination or had had endoscopic examination more than 2 years before the detection of gastric cancer (group 2). For the evaluation of survival rate, the patients in each group were classified into two subgroups: group 1a, endoscopic examination within 1 year before detection; group 1b, endoscopic examination more than 1 year and within 2 years; group 2a, endoscopic examination more than 2 years and within 4 years before detection; and group 2b, endoscopic examination more than 4 years before detection, or no endoscopic examination. RESULTS: Gastric cancer in group 1 was characterized by small tumor size, no tumor invasion beyond the submucosa, few instances of lymphatic and vascular permeation, and few lymph node metastases. The 5-year survival rate for group 1 patients (96.5%) was significantly higher than that for group 2 patients (71.0%; P < 0.01). The survival rates for group 1a patients and group 1b patients were not significantly different (P = 0.4595). The survival rate for patients in group 2a was significantly lower than that for those in group 1a (P < 0.05). CONCLUSION: Periodic gastric endoscopy enables early detection of cancer, thereby improving survival. The optimal interval for periodic examination appears to be 2 years. PMID- 11760077 TI - Adequate endoscopic mucosal resection for early gastric cancer obtained from the dissecting microscopic features of the resected specimens. AB - BACKGROUND: We have employed endoscopic mucosal resection (EMR), using a cap fitted panendoscope (EMRC), for early gastric cancer since 1992. The presence of an adequate surgical margin is a requirement because of the radicality of EMR, and dissecting microscopic examination is useful in regard to the diagnosis of spread of the disease. METHODS: To devise an adequate method of EMR that allows no lateral residue, we examined gastric mucosal specimens obtained by EMRC. One hundred and sixty-seven specimens from 97 lesions in 85 patients treated by EMRC were examined in regard to characteristic features, the recovery of marks made around the lesion, and the frequency of residue, and comparisons were made between the dissecting microscopic and histopathological findings. RESULTS: The first specimen obtained with a large cap under full suction was a circular shape measuring 21 x 19mm. The second specimen from fractionated resection was a half moon or crescent shape, and the third specimen had a ginkgo leaflike or irregular shape. In the elevated lesions, coincidence regarding the spread, as determined by dissecting microscopy and histopathology, was present in 62 (93%) of the 67 lesions. In 16 (53%) of 30 flat or depressed lesions, there was a difference of 2 to 5 mm between the spread determined by these two examinations. CONCLUSION: It is important to place an adequate number of marks around the lesion and recover all marks by resection. When an elevated lesion measures 15mm or more, and a flat or depressed lesion is not clearly demarcated, aggressive use of planned fractionated resection seems to be the best way to prevent a lateral residue in EMR. PMID- 11760079 TI - Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European American lymphoma classification. AB - BACKGROUND: The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. METHODS: Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. RESULTS: According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). CONCLUSIONS: These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL. PMID- 11760080 TI - Combination chemotherapy of irinotecan plus cisplatin for advanced gastric cancer: efficacy and feasibility in clinical practice. AB - BACKGROUND: A previous phase II study showed that a combination of irinotecan (CPT-11) with cisplatin (CDDP) was effective for advanced gastric cancers, but was associated with substantial neutropenia and diarrhea. The aim of this retrospective study was to evaluate the efficacy and feasibility of the combination in clinical practice. METHODS: The subjects comprised 65 patients with advanced gastric cancer treated with CPT-11 (70mg/m2, day 1, day 15) and CDDP (80mg/m2, day 1) as first-line chemotherapy between April 1993 and March 1999. Patient backgrounds, response rates, response durations, times to progression, and survival rates were investigated retrospectively. RESULTS: The overall response rate and the response rates for measurable metastatic lesions and primary sites were 43% (28/65), 48% (31/64), and 24% (10/42). Leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in 6 (9%) and 5 (8%) patients, respectively. Among the 19 patients with peritoneal metastasis, leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in only 1 of the 18 patients who received sufficient oral intake (6%). There were no treatment-related or early deaths within 30 days from the last treatment day. The median survival times of all patients, patients with an intestinal type of adenocarcinoma, and patients with a diffuse type were 365, 472, and 291 days, respectively. Multivariate analysis showed that the histological type of cancer was a significant independent prognostic factor (P = 0.0169). CONCLUSION: This retrospective study confirmed the efficacy and feasibility of this combination therapy in clinical practice. PMID- 11760081 TI - Liver metastasis in gastric cancer with particular reference to lymphatic advancement. AB - BACKGROUND: We have previously reported that, in models of mesenteric lymph vessel obstruction in rats, we observed lymphaticovenous communication. This suggested that cancer cells metastasized to the liver by a lymphatic route. In the present study, we investigated the relationship between liver metastasis and lymphatic involvement in gastric carcinoma by examining resected specimens. METHODS: Twenty gastric cancer patients who had synchronous liver metastasis and 17 who developed metachronous liver metastasis after gastrectomy, performed between 1985 and 1997, were included in this study. They were compared with 44 advanced gastric cancer patients who had neither synchronous nor subsequent liver metastasis, and who survived with a disease-free course for more than 5 years. We compared the patients' clinicopathological features; in particular, we investigated extranodal invasion in the resected lymph nodes. This invasion was classified according to the pattern of extranodal cancer invasion, with or without rupture of the lymph node capsule. RESULTS: Liver metastasis was more frequent in patients with extranodal invasion than in those without extranodal invasion (P < 0.002). Multivariate analysis revealed that the correlation between extranodal invasion and liver metastasis was significant (P < 0.024); the odds ratio was 4.412. Metastasis to the lymph nodes was the next most significant risk for liver metastasis. CONCLUSION: We consider that the lymphatic system is closely related to the establishment of liver metastasis; in particular, extranodal invasion is a significant risk factor for liver metastasis in patients with gastric cancer. PMID- 11760082 TI - Long-term effects of jejunal pouch added to Roux-en-Y reconstruction after total gastrectomy. AB - BACKGROUND: Jejunal pouch reconstruction after total gastrectomy has been demonstrated to ameliorate postgastrectomy symptoms, with the process of adaptation taking several months. In contrast to the short-term effects of pouch reconstruction, there are few reports about the long-term consequences (more than 2 years after surgery). METHODS: In this study, 22 patients with jejunal pouch (PRY group) and 12 patients without jejunal pouch (RY group) who survived for more than 2 years without any recurrence and were available for follow-up were compared. Patients in the two groups were compared 2 years after surgery in terms of postgastrectomy symptoms, and improvements in body weight and nutritional parameters. RESULTS: Eating capacity at a single meal compared with that in the pre-illness state was significantly better in the PRY group than in the RY group. The total score on the gastrointestinal symptom rating scale (GSRS) in the PRY group was less than that in the RY group (3.17 vs 5.25). The GSRS score for reflux syndrome in the PRY group was significantly better than that in the RY group. Assessment according to Cuschieri's gradings revealed that the total score in the PRY group was lower than that in the RY group (2.73 vs 5.92). Among the various symptoms examined, the incidence of dietary restriction and that of heartburn were significantly lower in the PRY group. CONCLUSION: We conclude that, 2 years after total gastrectomy, the pouch reconstruction had alleviated postgastrectomy symptoms to a greater extent than simple Roux-en-Y reconstruction, but the effectiveness could be improved. The long-term effects of pouch reconstruction should be examined more precisely with an adequate and valid scoring system for determining quality of life. PMID- 11760083 TI - Gastric cancer in Mexico. PMID- 11760084 TI - Improve the outcome of autologous hematopoietic cell transplantation! PMID- 11760085 TI - Engineering hematopoietic grafts: purified allogeneic hematopoietic stem cells plus expanded CD8+ NK-T cells in the treatment of lymphoma. AB - A major benefit of allogeneic hematopoietic cell transplantation (HCT) in the treatment of malignancies is the graft-versus-tumor (GVT) effect conferred by lymphocytes contained within the graft. However, lymphocytes can also induce the potentially lethal complication of graft-versus-host disease (GVHD). We have previously reported a method of generating large numbers of ex vivo activated and expanded T cells with antitumor activity after culture with interferon-y, cross linking antibodies to CD3, and interleukin-2. Murine splenocytes expanded under these conditions are a heterogeneous population of which approximately 20% to 60% of cells express natural killer (NK)-cell markers (NK1.1 and DX5) and display major histocompatibility complex (MHC)-unrestricted antitumor activity. Here we demonstrate the in vivo antitumor activity of this population of expanded CD8+ NK T cells when transplanted across MHC barriers into tumor-bearing hosts. In cotransfer studies with purified allogeneic hematopoietic stem cells, expanded CD8+ NK-T cells confer GVT activity with minimal to no GVHD. In vitro studies show that, although expanded NK-T cells lyse normal allogeneic bone marrow cells, they preferentially mediate cytolysis against tumor targets. These cells persist in the peripheral circulation of host animals for at least 3 weeks posttransfer. GVT activity is dependent on perforin, but not on Fas-ligand. We conclude that expanded CD8+ NK-T cells may serve as a valuable adjuvant population for allogeneic HCT because they mediate GVT effects with minimal GVHD. PMID- 11760086 TI - Purified canine CD34+Lin- marrow cells transduced with retroviral vectors give rise to long-term multi-lineage hematopoiesis. AB - Human CD34+ cells have been shown to retain long-term hematopoietic engrafting potential in preclinical and clinical studies. However, recent studies of human and murine CD34- stem cells suggest that these are functionally important early progenitors. Using autologous transplantation, we investigated whether canine CD34 and CD34- marrow cells could be transduced and give rise to long-term hematopoiesis. CD34+Lin- and CD34-Lin- cell populations purified by fluorescence activated cell sorting were separately cocultivated with retroviral vectors LN (CD34+Lin-) and LNY (CD34-Lin-), which carry the neomycin (neo) gene. After myeloablative total body irradiation (920 cGy), 3 dogs received transplants of both CD34+Lin- cells and CD34-Lin- cells and 2 dogs received only CD34-Lin- cells. Untransduced autologous marrow cells were given to ensure hematopoietic recovery. Using CFU-C assays, transduction efficiencies of CD34+Lin- cells ranged from 6% to 18% with no CFU-C formation from CD34-Lin- cells. PCR-based detection of the neo gene from WBCs was used to detect transduced cells weekly after transplantation. Additional PCR studies in 3 dogs given both CD34+Lin- and CD34 Lin- cells were performed on monocytes, granulocytes, and T cells (2 dogs, one at 7.5 months and the other at 9 months) and granulocytes (1 dog at 12 months). LN was detected up to 12 months posttransplantation in WBCs and mono-myeloid and lymphoid populations from 3 dogs receiving transplants of transduced CD34+Lin- cells. LNY was not detected at any time after transplantation in 5 dogs that received transduced CD34-Lin- cells. Whereas canine CD34+Lin- marrow cells contributed to long-term multilineage hematopoiesis, progeny of CD34-Lin- progenitor cells were not detected after transplantation in these experiments. PMID- 11760087 TI - Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease. AB - High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/ 15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected. PMID- 11760088 TI - Allogeneic bone marrow transplantation in patients with sensitive low-grade lymphoma or mantle cell lymphoma. AB - PURPOSE: To report survival outcomes of allogeneic BMT in patients with low-grade lymphoma or mantle cell lymphoma (MCL). PATIENTS AND METHODS: Thirty-five patients with low-grade lymphoma (48%), chronic lymphocytic leukemia (26%), or MCL (26%) underwent myeloablative allogeneic BMT from HLA-identical siblings at the Johns Hopkins Oncology Center. Patients had a median age of 46 years, a median of 2 prior treatments, and 31% were in complete remission at the time of transplantation. The preparative regimen was cyclophosphamide/total body irradiation for most patients. All grafts were T-cell depleted by counter flow centrifugal elutriation with CD34+ augmentation. RESULTS: The incidence of acute GVHD grade >2 was 6% and of grades 1 to 2 was 37%. The incidence of chronic GVHD was 6%. The median follow-up time was 25 months. The rate of event-free survival (EFS) was 50% (95% confidence interval [CI], 33%-66%). Only 1 patient relapsed. The transplantation-related mortality (TRM) was 46% for all patients. The TRM was 86% for patients with resistant disease and 14% for patients with sensitive disease and <2 prior treatments; rates of EFS were 0% (95% CI, 0%-0%) and 79% (95% CI, 47%-93%), respectively. CONCLUSION: These data show that, with T-cell depletion, the TRM and relapse rates are modest for patients with sensitive disease and <2 prior treatment courses. Thus, if there is a role for allogeneic BMT in the management of patients with these tumors, it is early in the course of the disease. PMID- 11760089 TI - Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. AB - Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but are limited by the occurrence of GVHD. CD8+ T lymphocytes are involved in the pathogenesis of GVHD but may not be essential for the graft-versus-leukemia (GVL) effect in CML. We have treated 26 CML patients with posttransplantation relapse with CD8-depleted DLI. Thirteen of 15 patients (87%) who relapsed in early-phase CML achieved complete cytogenetic response, but only 1 of 11 who relapsed in advanced-phase disease achieved complete response. Acute GVHD occurred in 2 patients (8%), and extensive chronic GVHD occurred in 2 patients (11%). Treatment-related mortality was 11.5%. Responses were durable; with a median follow-up of 4.2 years (1-7.5 years), only 1 responding patient relapsed (7%). CD8-depleted DLI was equally effective and safe after unrelated donor transplants and sibling transplants. Cytogenetic clonal evolution at the time of DLI was not predictive of treatment failure unless associated with hematologic criteria for disease acceleration. CD8 depletion is an effective method to separate GVL from GVHD for posttransplantation relapsed CML. This strategy is associated with durable complete remissions and a low rate of complications and therefore merits further investigation in larger-scale comparative trials. PMID- 11760090 TI - The influence of health insurance on outcomes of related-donor hematopoietic stem cell transplantation for AML and CML. PMID- 11760091 TI - Cooling is a potent vasodilator of deep vessels in the rat. AB - The objectives of this study were to determine the effect of cooling on smooth muscle tone of the pulmonary artery and aorta and to clarify the basic mechanism of these responses. We recorded isometric tension in smooth muscle strips of rat pulmonary artery and aorta in organ baths during stepwise cooling. Cooling responses were tested before and after the addition of various standard agents that interfere with known neurogenic (autonomic blockers, tetrodotoxin) and myogenic mechanisms (calcium channel blockers) of relaxation. We also examined the hypothesis of the presence of a cooling-released substance. Stepwise cooling (37degrees C to 4 degrees C) of aortic smooth muscle induced reproducible graded relaxations that were inversely proportional to temperature. Cooling-induced relaxation was not dependent on a neural mechanism nor the release of neurotransmitters or a cooling-released substance such as NO or CO. Cooling of pulmonary arterial and aortic smooth muscle preparations induced a graded myogenic relaxation inversely proportional to the cooling temperature. The mechanism is not dependent on local nervous or known mediators but related to a direct physico-chemical effect of cooling. PMID- 11760092 TI - The innervation of the human antro-pyloric region: organization and composition. AB - Although the composition of the gastric innervation has been determined in animal models, relatively little known about the innervation of the human antro-pyloric region. We used immunocytochemical techniques to establish the localization and co-expression of neuropeptides and nitric oxide in the human antrum and upper duodenum. Our results demonstrate the existence of a clearly defined submucosal plexus in the antral region that is absent in rats and guinea pigs. The abundant innervation of the lamina propria contains 3 major nerve populations: VIP- and NOS-, SP- and CGRP-, and GRP-immunoreactive. For the first time, NOS-containing nerve fibers were observed throughout the length of the antral glands. Within the antrum somatostatin was confined to endocrine cells, however, at the pyloric sphincter both enteric plexi contained immunoreactive neurons and nerve fibres. Within the pyloric sphincter CGRP- and SP-immunoreactive fibres were significantly increased, correlating with the presence of large ganglia in the submucosal plexus. In conclusion, the organization and composition of the innervation of human antro-pylorus differed substantially from that reported in other mammals. The presence of an abundant mucosal innervation paralled by a well defined submucosal plexus indicates that the functional regulation of the gastric pyloric region will be distinct from that of smaller animal models. PMID- 11760093 TI - Ammonium ion enhances the calcium-dependent gating of a mammalian large conductance, calcium-sensitive K+ channel. AB - We observed that the current amplitude and activation of expressed, mouse brain large conductance, calcium-sensitive K+ channels (BKCa channels) may be reversibly enhanced following addition of low concentrations of the weakly permeant cation NH4+ to the cytoplasmic face of the channel in excised, inside out membrane patches from HEK 293 cells. Conductance-voltage relations were left shifted along the voltage axis by addition of NH4Cl in a concentration-dependent manner, with an EC50 of 18.5 mM. Furthermore, this effect was observed in the presence of cytosolic free calcium (approximately 1 microM), but was absent in a cytosolic bath solution containing nominally zero free calcium (e.g.. 5 mM EGTA only), a condition under which these channels undergo largely voltage-dependent gating. Recordings of single BKCa channel events indicated that NH4+ increased the channel open probability of single channel activity approximately 3-fold, but did not alter the amplitude of single channel currents. These findings suggest that the calcium-sensitive gating of mammalian BKCa channels may be modified by other ions present in cytosolic solution. PMID- 11760094 TI - EDHF mediates the relaxation of stretched canine femoral arteries to acetylcholine. AB - To test the hypothesis that mechanically stretched arteries relax to endothelium derived vasodilators, we challenged endothelium-intact dog femoral artery rings stretched from 1 to 16 g total initial tension (active force and passive elastic) with 10(-6) M acetylcholine (ACh), an endothelium-dependent dilator. The relaxation to 10(-6) M sodium nitroprusside (SNP), an endothelium-independent dilator, increased with the total initial tension. The relaxation to ACh averaged approximately 65% of the relaxation to SNP at total initial tensions of 4 to 16 g. To determine the nature of the endothelial-derived products involved, we compared the ACh-induced relaxation of stretched rings (6.5 +/- 0.2 g total initial tension) with rings chemically contracted with phenylephrine (Phe, 10(-7) to 10(-5) M) (6.5 +/- 0.3 g total initial tension). ACh-induced relaxation was evaluated before and after the inhibition of the synthesis of eicosanoids [cyclooxygenase (10(-5) M indomethacin) and lipoxygenase (10(-5) M nordihydroguariaretic acid)] and nitric oxide [nitric oxide synthase (10(-5) M Nw nitro-L-arginine)]. The contribution of endothelium-derived hyperpolarizing factor (EDHF) was identified by blocking calcium-activated potassium channels (10(-8) M iberiotoxin). SNP (10(-6) M) relaxed stretched rings by 1.7 +/- 0.1 g and chemically-activated rings by 4.8 +/- 0.2 g. ACh relaxed stretched rings to 73 +/- 3% of the SNP relaxation and this was only attenuated in the presence of iberiotoxin. ACh relaxed Phe-activated rings to 60 +/- 3% of the SNP relaxation. This relaxation was attenuated by inhibition of the synthesis of nitric oxide and (or) eicosanoids. Therefore, ACh relaxed stretched rings through the release of EDHF whereas the relaxation of chemically activated rings to ACh involved multiple endothelium-derived vasodilators. PMID- 11760095 TI - Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle. AB - The present study compared ouabain-sensitive unidirectional K+ flux into (JinK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and mouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibited 54 +/- 4% of the total JinK in 28 +/- 1 min, and increased the net and unidirectional efflux of K+ within 4 min. In contrast, 1.8 mM ouabain inhibited 40 +/- 8% of the total JinK in 38 +/- 2 min, but did not significantly affect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater extent (83 +/- 5%) than in situ, but did not significantly affect 42K loss rate compared with controls. The increase in unidirectional K+ efflux (JoutK) with 5 mM ouabain in situ was attributed to increased K+ efflux through cation channels, since addition of barium (1 mM) to ouabain-perfused muscles returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouabain plus 2 mM tetracaine for 30 min decreased JinK 46 +/- 9% (0.30 +/- 0.03 to 0.16 +/- 0.02 micromol x min(-1) x g(-1)), however tetracaine was unable to abolish the ouabain-induced increase in unidirectional K+ efflux. In both rat hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of hindlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+ channel blocker) decreased JinK by 15 +/- 1%, but had no effect on JoutK; subsequent addition of ouabain (5 mM) decreased JinK a further 32 +/- 2%. The ouabain induced increase in unidirectional K+ efflux did not occur when TTX was perfused prior to and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain increases the unidirectional efflux of K+ from skeletal muscle through a barium and TTX-sensitive pathway, suggestive of voltage sensitive Na+ channels, in addition to inhibiting Na+/K+-ATPase activity. PMID- 11760096 TI - The role of the placenta in variability of fetal exposure to cocaine and cannabinoids: a twin study. AB - There is wide variability in the reported adverse fetal effects of cocaine and cannabinoids. The causes of this variability are largely unknown. We hypothesized that variability in placental handling of drugs affect fetal exposure. We used twin pregnancies as a paradigm to address the role of the placenta in this variability. We analyzed hair or meconium samples taken from dizygotic and monozygotic twins exposed in utero to illicit drugs. Out of 12 pairs, 5 had negative levels in both twins, and seven pairs of twins had chemical evidence of fetal exposure to cocaine (n = 5) or cannabinoids (n = 2). The one known monozygotic pair of twins had almost identical levels of cocaine. In contrast, the six dizygotic pairs had large disparities in either cocaine or cannabinoid concentrations. In three of these six dizygotic pairs, levels of cocaine (n = 2) or canabinoids (n = 1) were undetectable in one twin while positive in the other. Given that twins are theoretically exposed to similar maternal drug levels, our findings suggest that the placenta may have a major role in modulating the amounts of drug reaching the fetus. PMID- 11760097 TI - Effect of antidepressants on ATP-dependent calcium uptake by neuronal endoplasmic reticulum. AB - This study investigated the effect of tricyclic and atypical antidepressants on adenosine triphosphate (ATP) dependent calcium uptake by the endoplasmic reticulum of lysed synaptosomes from rat brain cortex. Tricyclic antidepressants (imipramine, desipramine, clomipramine, amitriptyline) exhibited no effect in the lower range (0.06 to 2 microM) of drug concentrations, and a concentration dependent inhibition of calcium uptake in the upper range (6 to 200 microM). A concentration-dependent inhibition was observed for atypical antidepressants (mianserin, desmethylmianserin, venlafaxine, desmethylvenlafaxine, fluoxetine) in both the lower and the upper range of drug concentrations. Since no stimulation of calcium uptake was observed in either concentration range, it appears that the tricyclic and atypical antidepressants tested are not capable of normalizing, through their effect on the endoplasmic reticulum, an overactive calcium signal. which is possibly implicated in the etiology of affective disorders. Also, although only marginal inhibition of calcium uptake is expected at brain concentrations of tricyclics and mianserin-desmethylmianserin that are likely to be encountered during clinical use, a more substantial inhibition could occur with fluoxetine. PMID- 11760099 TI - Oxygen sensitive chemoreceptors in the first gill arch of the tadpole, Rana catesbeiana. AB - Spike frequency was recorded in the nerve of the isolated superfused first gill arch of the bullfrog larva, Rana catesbeiana and the response to different superfusate PO2 was evaluated. In the metamorphic tadpole, spike frequency increased significantly when the superfusate PO2 was decreased (mean +/- SEM): 8.5 +/- 1.6 Hz at 650 Torr, 11.7 +/- 1.9 Hz at 140 Torr, 13.3 +/- 1.8 Hz at 65 Torr, 14.8 +/- 2.4 Hz at 0 Torr (ANOVA, p = 0.0002). The O2 sensitive chemoreceptor stimulants NaCN and almitrine also increased the spike frequency. This study demonstrates the presence of O2 sensitive chemoreceptors in the first gill arch of the tadpole. PMID- 11760098 TI - Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism. AB - Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5alpha spirostan-3beta-yl 4-O-[2-0-[3-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl] 3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyl] 3-D- galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2, (25R)-5alpha spirostan-3beta-yl 4-O-[2-0-[3-0-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl]-3 0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D glucopyranosyl]beta-D-galactopyranoside), were isolated from the fresh bulbs of Camassia cusickii. In murine leukemic L1210 cells, both compounds showed cytotoxicity with an EC50 value of 0.06 microM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. The cell death was confirmed to be apoptosis by Annexin V binding to phosphatidylserine in the cell membrane and excluding propidium iodide. A typical apoptotic DNA ladder and the cleavage of caspase-3 were observed after treatment with TGHS-1 and TGHS-2. In the presence of both the compounds, cells with sub-G1 DNA content were detected by flow cytometric analysis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 microM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation. PMID- 11760100 TI - Understanding birthing mode decision making using artificial neural networks. AB - BACKGROUND: This study examined obstetricians' decisions to perform or not to perform cesarean sections. The aim was to determine whether an artificial neural network could be constructed to accurately and reliably predict the birthing mode decisions of expert clinicians and to elucidate which factors were most important in deciding the birth mode. METHODS: Mothers with singleton, live births who were privately insured, nonclinic, non-Medicaid patients at a major tertiary care private hospital were included in the study (N = 1508). These mothers were patients of 2 physician groups: a 7-obstetrician multispecialtygroup practice and a physician group of 79 independently practicing obstetricians affiliated with the same hospital. A feedforward, multilayer artificial neural network (ANN) was developed and trained. It was then tested and optimized until the most parsimonious network was identified that retained a similar level of predictive power and classification accuracy. The performance of this network was further optimized using the methods of receiver operating characteristic (ROC) analysis and information theory to find the cutoff that maximized the information gain. The performance of the final ANN at this cutoff was measured using sensitivity, specificity, classification accuracy, area under the ROC curve, and maximum information gain. RESULTS: The final neural network had excellent predictive accuracy for the birthing mode (classification accuracy = 83.5%; area under the ROC curve = 0.924; maximum information = 40.4% of a perfect diagnostic test). CONCLUSION: This study demonstrated that a properly optimized ANN is able to accurately predict the birthing mode decisions of expert clinicians. In addition to previously identified clinical factors (cephalopelvic disproportion, maternal medical condition necessitating a cesarean section, arrest of labor, malpresentation of the baby, fetal distress, andfailed induction), nonclinical factors such as the mothers' views on birthing mode were also found to be important in determining the birthing mode. PMID- 11760101 TI - Intermediate short-term outcomes after brain computed tomography and magnetic resonance imaging in neurology outpatients. AB - OBJECTIVE: The purpose of this study was to assess and compare the impact of magnetic resonance imaging (MIR) and computed tomography (CT) on diagnostic and therapeutic decision making, taking into account the real cost of both techniques at the authors' institution. METHOD: Brain CT and routine and rapid MRI were compared, and case files were prepared with either the CT or the MRI findings. These files were separately presented to a neurologist, and different questions were asked about further management. The real cost of CT and MRI was calculated. A questionnaire was sent to the patients 3 months after imaging. RESULTS: More lesions were detected on MRI than on CT Routine and rapid AIRI were comparable. The analysis of the CT case files revealed an additional request for MRl in 33% of the patients. An analysis of the MRI case files revealed that 20% more technical examinations were requested after MRI than after CT In the majority of the patients (90%), neuroimaging had no impact on therapy except by means of reassurance of the physician. The scan was considered useful for therapeutic planning by excluding the presence of a space-occupying lesion. The real cost of the MP! strategy was 9% higher than that of the CT strategy. CONCLUSION: In this patient population, neuroimaging was normal in the majority of the patients. Undergoing an imaging examination was of benefit to the patients and improved their sense of well-being mainly by the reassurance they experienced, as reported by 91% of the patients. At the authors' institution, the real cost of MMI in this patient population was only slightly higher than the real cost of CT The statistical analysis favors the use of MRI as a 1st imaging examination. PMID- 11760102 TI - A cost-effectiveness analysis of alternative at-home or in-laboratory technologies for the diagnosis of obstructive sleep apnea syndrome. AB - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder that affects 2% to 9% of the population. Health care policy makers have noted increased referrals for sleep studies. OBJECTIVE: In this article, the authors conduct a cost-effectiveness analysis to determine the optimal technology for the diagnosis of OSAS using polysomnography (PSG) or partial sleep monitoring (PSM). DESIGN: The target population was a hypothetical cohort of patients suspected of having OSAS. A 2-level decision tree wasformulated that reflects all possible steps of OSAS diagnosis and therapy. The method represents a comprehensive strategy to determine which of the 2 systems-PSG or PSM-has cost advantages. The financial and operational aspects of OSAS diagnosis and therapy were analyzed. A sensitivity analysis was performed over all uncertain parameters (i.e., diagnostic agreement, data loss, and referral to therapy). RESULTS: Unattended at home sleep monitoring was the most expensive method. The combination of 1:2 PSG and attended PSM strategy was the optimal strategy with respect tofinancing and operations. Compared to the PSG-only strategy, this combination may lead to a 10% reduction of the annual expenditure. CONCLUSION: This study provides proof of concept (under a wide range of sensitivity assumptions) that the cost of sleep study techniques can be modeled. It rejects the assumption that athome portable sleep monitoring is cost advantageous. The combination of PSG and attended PSM OSAS is the most cost-effective approach to sleep evaluation. PMID- 11760103 TI - Frequency or probability? A qualitative study of risk communication formats used in health care. AB - BACKGROUND: The communication of probabilistic outcomes is an essential aspect of shared medical decision making. METHODS: The authors conducted a qualitative study using focus groups to evaluate the response of women to various formats used in the communication of breast cancer risk. FINDINGS: Graphic discrete frequency formats using highlighted human figures had greater salience than continuous probability formats using bar graphs. Potential biases in the estimation of risk magnitude were associated with the use of highlighted human figures versus bar graphs and the denominator size in graphics using highlighted human figures. The presentation of uncertainty associated with risk estimates caused some to loose trust in the information, whereas others were accepting of uncertainty in scientific data. CONCLUSION: The qualitative studyidentified new constructs with regard to how patients process probabilistic information. Further research in the clinical setting is needed to provide a theoretical justification for the format used when presenting risk information to patients. PMID- 11760104 TI - Using life expectancy to communicate benefits of health care programs in contingent valuation studies. AB - BACKGROUND: There is growing interest in the use of contingent valuation (CV) to estimate the monetary value of health program benefits. Ideally, CV could be used to value a specific shift in survival curve. However, a shift in survival curve may prove too complex for widespread use in CV instruments. To facilitate the use of CV in valuing longevity benefits, researchers need alternative summary measures that describe the longevity benefit in a single number that is more readily communicated in a CV context. METHODS: The authors compare 2 methods for communicating longevity benefits in a CV survey. Random subsamples of respondents valued a longevity benefit expressed either as a continuing reduction in annual mortality risk or as a gain in life expectancy. To compare the validity of the alternative descriptions, the authors evaluate willingness to pay (WTP) estimates for consistency with theoretical predictions. RESULTS: It is found that WTP for a longevity benefit is sensitive to the framing of the benefit, with respondents expressing higher WTP for the benefit expressed as a life expectancy gain. The life expectancy format performs better than the risk reduction format in one important regard-sensitivity to scope of the benefit-and no worse than the risk reduction format in other regards. CONCLUSION: Expressing longevity benefits in terms of life expectancy appears to hold promise as a method for enhancing the validity of economic evaluation of health care programs. PMID- 11760105 TI - What white blood cell count should prompt antibiotic treatment in a febrile child? Tutorial on the importance of disease likelihood to the interpretation of diagnostic tests. AB - Most diagnostic tests are not dichotomous (negative or positive) but, rather, have a range of possible results (very negative to very positive). If the pretest probability of disease is high, the test result that prompts treatment should be any value that is even mildly positive. If the pretest probability of disease is low, the test result needed to justify treatment should be very positive. Simple decision rules that fix the cutpoint separating positive from negative test results do not take into account the individual patient's pretest probability of disease. Allowing the cutpoint to change with the pretest probability of disease increases the value of the test. This is primarily an issue when the pretest probability of disease varies widely between patients and depends on characteristics that are not measured by the test. It remains an issue for decision rules based on multiple test results if these rules fail to account for important determinants of patient-specific risk. This tutorial demonstrates how the value of a diagnostic test depends on the ability to vary the cutpoint, using as an example the white blood cell count in febrile children at risk for bacteremia. PMID- 11760106 TI - Comparison of appropriateness ratings for cataract surgery between convened and mail-only multidisciplinary panels. AB - BACKGROUND: In this article, the authors determine the reproducibility of appropriateness ratings for cataract surgery between a multidisciplinary physician panel that convened and a multidisciplinary physician panel that completed ratings by mail. METHODS: Eighteen panelists, who constituted 2 distinct multidisciplinary panels, rated 2894 clinical scenarios as an appropriate, inappropriate, or uncertain indication to perform cataract surgery. Each panel's summary score for each scenario was calculated. Weighted kappa values were determined to assess the level of agreement between the ratings of the 2 panels. RESULTS: The panels had a substantial level of agreement overall, with a weighted kappa statistic of 0.64. There was agreement on about 68% of the scenarios, and serious disagreement, in which one panel rated an indication appropriate and the other rated it inappropriate, occurred in only 1% of the ratings. CONCLUSION: There was substantial agreement about the ratings by the 2 panels. The panel that convened rated fewer scenarios uncertain and more appropriate, suggesting the impact of group dynamics and face-to-face discussion on resolution of uncertainty. PMID- 11760107 TI - Intervals for posttest probabilities: a comparison of 5 methods. AB - BACKGROUND: Several medical articles discuss methods of constructing confidence intervals for single proportions and the likelihood ratio, but scant attention has been given to the systematic study of intervals for the posterior odds, or the positive predictive value, of a test. METHODS: The authors describe 5 methods of constructing confidence intervals for posttest probabilities when estimates of sensitivity, specificity, and the pretest probability of a disorder are derived from empirical data. They then evaluate each method to determine how well the intervals' coverage properties correspond to their nominal value. RESULTS: When the estimates of pretest probabilities, sensitivity, and specificity are derived from more than 80 subjects and are not close to 0 or 1, all methods generate intervals with appropriate coverage properties. When these conditions are not met, however, the best-performing method is an objective Bayesian approach implemented by a simple simulation using a spreadsheet. CONCLUSION: Physicians and investigators can generate accurate confidence intervals for posttest probabilities in small-sample situations using the objective Bayesian approach. PMID- 11760109 TI - Determining the area under the receiver operating characteristic curve for a binary diagnostic test: best is not always ideal. PMID- 11760108 TI - Law and ethics: the physician as learned intermediary and when a clinical trial is in a developing country: the protection of human subjects. PMID- 11760110 TI - The aftermath: knowledge and uncertainty. PMID- 11760111 TI - Predicting length of stay in an acute care hospital: the role of psychosocial problems. AB - In an acute care hospital, a major performance indicator is patient length of stay. This study, in a large university teaching acute care hospital in Canada, examined the effect of psychosocial problems on length of stay, controlling for patient demographics and medical condition. Average days stay for Diagnostic Related Groups (DRGs) was used as a proxy variable for severity of medical condition, and the Person-in-Environment (PIE) classification system was used to measure psychosocial problems. Data were collected on a sample of 160 patients; 78 in psychiatry and 82 in medical/surgical wards. In a regression analysis, the severity of the patient's psychosocial problem was a more significant predictor of length of stay than the DRG variable. The identification of psychosocial problems and their severity add an important and complementary dimension to research into the effectiveness of social workers in reducing length of stay. Workers found clients had significantly more problems related to their social role functioning than problems in the environment. PMID- 11760112 TI - Deconstructing the ailment: one health care professional's experience as the patient. AB - This essay explores an illness in a health care professional through lenses of role flexibility and professional accountability. It highlights the process of contemplation about the dual identifications implicit in the experience of being both a professional and a patient within one health care delivery system. This can be a position of standing on the borders of possibility. Thus, the dilemma of a "wounded healer" may challenge some assumptions inherent in the giving and receiving of care as well as grant us some regard for the power shifts within the management of our patients and of ourselves. The experience that one's ailment can be an opportunity-to explore notions of sickness and health or to help to tease out the limits or the potential impact of our responsibility toward that which we name disease and cure-may be the more salient message. PMID- 11760113 TI - Can physicians' admission evaluation of patients' status help to identify patients requiring social work interventions? AB - OBJECTIVE: To evaluate the utility of these physicians' initial clinical assessments in identifying patients admitted from their homes who subsequently require social work intervention for discharge planning. DESIGN: Retrospective chart review of discharge disposition correlated with a prospective physician evaluation of patients. SETTING: An academic medical center. PARTICIPANTS: Consecutive patients, (2,571) men and women, admitted at the New York Hospital between July 1, 1997 and October 31, 1997. MEASUREMENT: Prospective evaluation of clinical status, functional status, illness severity and stability by physicians within 24 hours of admission. RESULTS: Older patients, sicker and less functional, have higher needs for social work intervention (P < 0.001). New nursing home placement patients were older and had worse function (P < 0.001). Total cost of hospitalization and length of stay were predicted by discharge disposition. CONCLUSION: Early discharge intervention has often been targeted as a potential mechanism to lower hospitalization cost and reduce length of stay. Age and physician evaluation of functional status at admission may provide early identification of those who require social work assistance. PMID- 11760114 TI - The cost of caring for patients with an illness: contagion to the social worker. AB - This article will examine the effects of hospital work on social workers. It will highlight the events of a focus group that was used to gather data in an attempt to begin to understand the stressors faced by the worker. The Self-Constructivist Model (McCann & Pearlman, 1990b) is utilized in relation to trauma experienced by the social worker, while working with patients diagnosed with an acute, chronic or life-threatening illness. Findings are summarized and recommendations are made to assist hospital social workers in coping with the aftermath of secondary trauma. PMID- 11760115 TI - Supportive relationships among hemodialysis recipients at a remodeled kidney center. AB - This study investigates the importance of social time spent at a remodeled kidney center among hemodialysis recipients. Twenty hemodialysis treatment recipients were selected to participate in semi-structured interviews to determine how they perceived the time spent at a kidney center. These twenty treatment recipients had received chronic dialysis treatment for at least one year, and were able to articulate an awareness of themselves within a community of other treatment recipients. Although the newly remodeled kidney center prevented unhampered communication with one another while receiving hemodialysis treatment, the recipients were able to generate supportive conversations and relationships in the waiting room and at the kidney center. PMID- 11760116 TI - Impact of social support, diversity, and poverty on nursing home utilization in a nationally representative sample of older Americans. AB - This study examined the effects of social support, poverty, functional status, and demographic variables (age, race, gender) on nursing home admission using Cox proportional hazard models with time varying covariates on the Longitudinal Study on Aging (1984-1990). The Behavioral Model of Health Care Utilization was used to organize the study. Living with a spouse or children reduced the risk as did being socially active. High income reduced the risk but there were problems in the measurement of income. Higher levels of functional disability predicted higher risk. Being Black or being female reduced the risk of admission. Age was a predictor of increased risk. Beyond these findings this paper provides support for the importance of gathering and utilizing data that allows for predictor variables to vary with time. PMID- 11760117 TI - The impact of ethnic identity upon the adjustment and satisfaction of Jewish and African American residents in a long-term care facility. AB - The role of ethnicity in shaping the adjustment process and satisfaction level of cognitively intact older adults with nursing home living is examined in two predominant ethnic groups in an 816 bed long-term care facility. A convenience sample was used to select 71 Jewish and 21 African American residents age 65 and older. Face-to-face interviews were conducted at a single point in time and incorporated four scales that measure strength of ethnic identity, adjustment and satisfaction with residency. Ethnic behavior was the only ethnic identity measure that was significantly associated with resident adjustment and with satisfaction. The two ethnic groups did not differ significantly in the association of ethnic identity with adjustment and satisfaction. Additional research will be necessary to establish the generalizability of these results to other ethnic and racial groups. PMID- 11760118 TI - Application of the S-pyridylethylation reaction to the elucidation of the structures and functions of proteins. AB - Cysteine (Cys) and cystine residues in proteins are unstable under conditions used for acid hydrolysis of peptide bonds. To overcome this problem, we proposed the use of the S-pyridylethylation reaction to stabilize Cys residues as pyridylethyl-cysteine (PEC) protein derivatives. This suggestion was based on our observation that two synthetic derivatives formed by pyridylethylation of the SH group of Cys with either 2-vinylpyridine (2-VP) or 4-vinylpyridine (4-VP), designated as S-beta-(2-pyridylethyl)-L-cysteine (2-PEC) and S-beta-(4 pyridylethyl)-L-cysteine (4-PEC), were stable under acid conditions used to hydrolyze proteins. This was also the case for protein-bound PEC groups. Since their discovery over 30 years ago, pyridylethylation reactions have been widely modified and automated for the analysis of many structurally different proteins at levels as low as 20 picomoles, to determine the primary structures of proteins and to define the influence of SH groups and disulfide bonds on the structures and functional, enzymatic, medical, nutritional, pharmacological, and toxic properties of proteins isolated from plant, microbial, marine, animal, and human sources. Pyridylethylation has been accepted as the best method for the modification of Cys residues in proteins for subsequent analysis and sequence determination. The reaction has also been proposed to measure D-Cys, homocysteine, glutathione, tryptophan, dehydroalanine, and furanthiol food flavors. This integrated overview of the diverse literature on these reactions emphasizes general concepts. It is intended to serve as a resource and guide for further progress based on the reported application of pyridylethylation reactions to more than 150 proteins. PMID- 11760119 TI - Adherence of vancomycin to proteins. AB - Vancomycin possesses the unusual property of promoting the aggregation of proteins. It also binds to itself (dimerization). Both properties may be related to its antimicrobial activity and we report here procedures to measure them. The position of the negative ellipticity band in the near ultraviolet circular dichroism spectrum of the vancomycin monomer shifts as a function of antibiotic concentration and can be used to readily determine the monomer-dimer equilibrium constant. These measurements complement those performed by high-resolution gel filtration to measure the same process. Aggregation of purified proteins was determined by turbidity measurements. Both dimerization and protein aggregation are influenced by anions whose effectiveness is related to their carboxyl pKa values, thus linking these two properties. PMID- 11760120 TI - The interaction of azide with polyphenol oxidase II from tobacco. AB - Spectroscopy studies of absorption and circular dichroism of native PPO II and azide PPO II complex demonstrate two new absorptions at 375 nm and 500 nm after azide's binding with PPO II, which are assigned as the terminal azide to copper charge transfer transitions II(o)nb-to-copper and II(v)nb-to-copper charge transfer transitions respectively. FT-IR spectra also demonstrate that the azide binds in terminal geometry with one of type-3 coppers. The interaction between azide and PPO II is discussed. One terminal azide's binding with one type-3 copper improves the activity of PPO II and the other three azides' further binding in terminal geometry with the type-3 coppers decreases the activity. We theorize that steric hindrance of azides makes oxygen difficult to bind in the active site. PMID- 11760121 TI - Purification and characterization of a new plant endopeptidase isolated from latex of Asclepias fruticosa L. (Asclepiadaceae). AB - Asclepias fruticosa L. is a small shrub containing latex with proteolytic activity. The crude extract (latex diluted 1:250 and ultracentrifuged) contained 276 microg of protein/mL and the proteolytic activity reached 1.2 caseinolytic U/mL. This enzyme preparation was very stable even after 2 hours at 45 degrees C, but was quickly inactivated after 5 minutes at 80 degrees C. Chromatographic purification was achieved by FPLC using a cation exchanger (SP-Sepharose FF). Thus, a unique proteolitically active fraction could be isolated, being homogeneous by bidimensional electrophoresis and mass spectrometry (Mr = 23,652). The optimum pH range was achieved at 8.5-10.5. The enzyme activity was completely inhibited by specific cysteine peptidases inhibitors. Isoelectric focusing followed by zymogram showed the enzyme had a pI greater than 9.3. The N-terminus sequence (LPDSVDWREKGVVFPIRNQGK) shows a great deal of similarity to those of the other cysteine endopeptidases isolated from latices of Asclepiadaceae even when a high degree of homology could be observed with other plant cysteine endopeptidases. PMID- 11760122 TI - Kinetics of the chemiluminescence associated to the reaction between peroxyl radicals and proteins. AB - Protein oxidation, mediated by peroxyl radicals derived from 2,2'-azobis(2 amidinopropane) dihydrochloride is sided by a significant visible chemiluminescence (CL). The light emission shows a complex dependence with the protein concentration and with the incubation time that cannot be interpreted in terms of peroxyl radicals recombination (Russell's mechanism). In all the systems studied, the chemiluminescent behavior requires to consider the participation of several oxidation products as precursors of the excited states. These compounds lead to the formation of excited states by competing radical and nonradical mediated pathways. These intermediates (most probably hydroperoxide-like compounds) would arise from the oxidation of Trp and Tyr residues. This conclusion is based on the similarity of the time profile of the chemiluminescence observed in the oxidation of the free amino acids and the proteins, both in the presence of and absence of free-radical scavengers. PMID- 11760123 TI - The regulation of surface charged residues on the properties of cytochrome b5. AB - To understand the roles of negatively surface charged residues, the cytochrome b5 (Cyt b5) E48A/D60A mutant was constructed. UV-visible and CD spectra confirmed that the mutation did not cause overall structural changes of the protein. The mutant presents an unexpected high stability toward the thermal and denaturant compared with the wild type Cyt b5, which shows that these surface charged residues can influence the interactions between the heme b group and the polypeptide chain. Functional properties were clarified through the electron transfer reactions between Cyt b5 and Cyt c. The driving force of the electron transfer reactions is conservative. Although the association constant of Cyt b5 E48A/D60A with Cyt c is much lower than that of the wild type Cyt b5, their electron transfer rate constants do not differ significantly. The results show that these surface charged residues play important roles in regulating both the stability and functional properties of Cyt b5. PMID- 11760124 TI - Isolation and characterization of isolectins from Talisia esculenta seeds. AB - Four isolectins (TEL-I, TEL-II, TEL-III and TEL-IV) were isolated from seeds of Talisia esculenta by reverse-phase high-performance liquid chromatography. RP HPLC was performed on a u-Bondapack C18 column (0.78 cm x 30 cm) (Waters 991-PDA system) at room temperature. Rechromatography of the four fractions on a C18 column under the same conditions yielded lectins with two dissimilar subunits (Mr 20 kDa and 40 kDa) bound noncovalently. The isolectins showed very similar characteristics, such as molecular masses, N-terminal sequences, and hemagglutinating activity, but differed in their isoelectric points and in inhibition by carbohydrates. PMID- 11760125 TI - Structure of the Bacillus subtilis peptide antibiotic subtilosin A determined by 1H-NMR and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. AB - Subtilosin A produced by Bacillus subtilis is a macrocyclic peptide antibiotic which comprises 35 amino acids. Its molecular mass (3399.7 Da), determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and chemical properties gave experimental support for unusual intramolecular linkages. The three-dimensional fold of native subtilosin in dimethylsulfoxide was determined from two-dimensional 1H-NMR spectra recorded at 600 MHz. Based on the backbone conformation, a structure for subtilosin A is presented which is characterized by three inter-residue bridges where two cysteines are linked with two phenylalanine residues, respectively, and a third cysteine is bound to a threonine residue. PMID- 11760126 TI - Characterization and use of green fluorescent proteins from Renilla mulleri and Ptilosarcus guernyi for the human cell display of functional peptides. AB - Green fluorescent protein (GFP) is useful as an intracellular scaffold for the display of random peptide libraries in yeast. GFPs with a different sequence from Aequorea victoria have recently been identified from Renilla mulleri and Ptilosarcus gurneyi. To examine these proteins as intracellular scaffolds for peptide display in human cells, we have determined the expression level of retrovirally delivered human codon-optimized versions in Jurkat-E acute lymphoblastic leukemia cells using fluorescence activated cell sorting and Western blots. Each wild type protein is expressed at 40% higher levels than A. victoria mutants optimized for maximum fluorescence. We have compared the secondary structure and stability of these GFPs with A. victoria GFP using circular dichroism (CD). All three GFPs essentially showed a perfect beta-strand conformation and their melting temperatures (Tm) are very similar, giving an experimental evidence of a similar overall structure. Folded Renilla GFP allows display of an influenza hemagglutinin epitope tag in several internal insertion sites, including one which is not permissive for such display in Aequorea GFP, giving greater flexibility in peptide display options. To test display of a functional peptide, we show that the SV-40 derived nuclear localization sequence PPKKKRKV, when inserted into two different potential loops, results in the complete localization of Renilla GFP to the nucleus of human A549 cells. PMID- 11760128 TI - Generalized common fate: grouping by common luminance changes. AB - A critical step toward object recognition is the segmentation of a scene into relevant regions. One of the most important cues for segmentation is that of common fate: Elements that move together are grouped together Here we describe a new instantiation of common fate, in which elements move together not through physical space, but through luminance space. Experiment I shows that when elements of a scene become brighter together or darker together, observers group those elements together Experiments 2 and 3 show that this effect is not due to the availability of fixed luminance differences between target and background regions, but requires common changes within each region in the direction of luminance over time. The effect is differentiated from the recently discovered grouping cue of temporal synchrony, and is considered instead to be an extension of Wertheimer's original grouping factor of common fate. Common fate for luminance, or generalized common fate, is an extremely strong cue for the segmentation of a scene, yielding a tremendous advantage over grouping by fixed luminance cues. PMID- 11760129 TI - The influence of native-language phonology on lexical access: exemplar-Based versus abstract lexical entries. AB - This study used medium-term auditory repetition priming to investigate word recognition processes. Highly fluent Catalan-Spanish bilinguals whose first language was either Catalan or Spanish were tested in a lexical decision task involving Catalan words and nonwords. Spanish-dominant individuals, but not Catalan-dominant individuals, exhibited repetition priming for minimal pairs differing in only one feature that is nondistinctive in Spanish (e.g.,[see text]), thereby indicating that they processed these words as homophones. This finding provides direct evidence both that word recognition uses a language specific phonological representation and that lexical entries are stored in the mental lexicon as abstract forms. PMID- 11760127 TI - In vacuo esterification of carboxyl groups in lyophilized proteins. AB - A new method is described for the esterification of carboxyl groups in proteins by reaction of the lyophilized protein in vacuo with gaseous alcohol and HCI catalyst. Carboxyl groups are rapidly esterified with no protein degradation. 13C Methyl or 13C-ethyl esters of the alpha-, gamma- and delta-carboxyl groups could be distinguished by the distinct chemical shifts of their resonances. Within the class of gamma- or delta-esters, the chemical shifts have little variation; however, the chemical shift of a C-terminal esterified alpha-carboxyl group shows a strong dependence on the nature of the C-terminal amino acid and sequence. Iodomethane reacts with deprotonated carboxyl groups in lyophilized proteins to form methyl esters, but unlike the reaction with gaseous methanol/HCI, it does not selectively methylate carboxyl groups. The procedure permits the cost effective incorporation of isotopic labels and provides a new approach using 13C NMR spectroscopy for determining the number of different C-termini present in a protein preparation. PMID- 11760130 TI - Culture, change, and prediction. AB - Five studies studies that Chinese and Americans perceive change differently. Chinese anticipated more changes from an initial state than Americans did. When events were changing in a particular direction. Chinese were more likely than Americans to predict change in the direction of change. Moreover, for patterns with changing slopes, Chinese predicted greater change in the way slopes changed, in comparison to Americans. In addition, people who predicted change were perceived as wise by Chinese more than by Americans. Implications for social attribution, tolerance for contradiction, persistence on tasks, and the illusion of control are discussed. PMID- 11760131 TI - Implementation intentions and facilitation of prospective memory. AB - Forming detailed implementation intentions for a future behavior can increase the probability that the behavior is actually completed. We investigated whether this intention effect could be used to improve prospective memory in older adults. As expected, participants who formed an implementation intention were more than twice as likely to self-initiate the intended behavior (writing down the day of the week on every sheet of paper received during the experiment) compared with participants who either were merely instructed to do so or actively rehearsed the instruction. Forming an implementation intention, however did not improve performance on a task that required a response to salient cues. We conclude that detailed implementation intentions facilitate prospective memory on tasks that lack salient cues and require self-initiation. PMID- 11760132 TI - Driven to distraction: dual-Task studies of simulated driving and conversing on a cellular telephone. AB - Dual-task studies assessed the effects of cellular-phone conversations on performance of a simulated driving task. Performance was not disrupted by listening to radio broadcasts or listening to a book on tape. Nor was it disrupted by a continuous shadowing task using a handheld phone, ruling out, in this case, dual-task interpretations associated with holding the phone, listening, or speaking, However significant interference was observed in a word generation variant of the shadowing task, and this deficit increased with the difficulty of driving. Moreover unconstrained conversations using either a handheld or a hands-free cell phone resulted in a twofold increase in the failure to detect simulated traffic signals and slower reactions to those signals that were detected. We suggest that cellular-phone use disrupts performance by diverting attention to an engaging cognitive context other than the one immediately associated with driving. PMID- 11760133 TI - Predicting the effects of actions: interactions of perception and action. AB - Many theories in cognitive psychology assume that perception and action systems are clearly separated from the cognitive system. Other theories suggest that important cognitive functions reside in the interactions between these systems. One consequence of the latter claim is that the action system may contribute to predicting the future consequences of currently perceived actions. In particular such predictions might be more accurate when one observes one's own actions than when one observes another person's actions, because in the former case the system that plans the action is the same system that contributes to predicting the action's effects. In the present study participants (N = 104) watched video clips displaying either themselves or somebody' else throwing a dart at a target board and predicted the dart's landing position. The predictions were more accurate when participants watched themselves acting. This result provides evidence for the claim that perceptual input can be linked with the action system to predict future outcomes of actions. PMID- 11760134 TI - Interviewing witnesses: forced confabulation and confirmatory feedback increase false memories. AB - In two experiments, adults who witnessed a videotaped event subsequently engaged in face-to-face interviews during which they were forced to confabulate information about the events they had seen. The interviewer selectively reinforced some of the participants' confabulated responses by providing confirmatory feedback (e.g., "Yes, ______ is the correct answer") and provided neutral (uninformative) feedback for the remaining confabulated responses (e.g., "O.K_____". One week later participants developed false memories for the events they had earlier confabulated knowingly. However confirmatory feedback increased false memory for forcibly confabulated events, increased confidence in those false memories, and increased the likelihood that participants wouldfreely report the confabulated events 1 to 2 months later The results illustrate the powerful role of social-motivational factors in promoting the development offalse memories. PMID- 11760135 TI - Paying attention to time as one gets older. AB - Age-related changes in attention and interval timing as a function of time of day were examined using a temporal bisection task with single and compound auditory and visual stimuli. Half of the participants in each age group were tested in the morning, and half were tested in the afternoon. Duration judgments were found to be shorter for visual signals than for auditory signals. This discrepancy was greater in the morning than in the afternoon and larger for the older than for the younger adults. Young adults showed equal sensitivity to signal duration for single and compound trials and higher sensitivity in the afternoon than in the morning for both signal modalities. In contrast, older adults showed impaired sensitivity on compound trials and the greatest sensitivity overall to single visual trials in the morning. These results suggest that age-related reductions in attentional resources may cause older adults to focus on signals that require controlled attention during specific phases of the circadian cycle. PMID- 11760136 TI - H.M., word knowledge, and aging: support for a new theory of long-term retrograde amnesia. AB - This study develops a new theory of long-term retrograde amnesia that encompasses episodic and semantic memory, including word knowledge. Under the theory, retrograde amnesia in both normal individuals and hippocampal amnesics reflects transmission deficits caused by aging, nonrecent use of connections, and infrequent use of connections over the life span. However, transmission deficits cause severe and irreversible retrograde amnesia only in amnesics who (unlike normal persons) cannot readily form new connections to replace nonfunctioning ones. The results of this study are consistent with this theory: For low frequency but not high-frequency words, a famous "hippocampal amnesic" (H.M.) at age 71 performed worse than memory-normal control participants in a lexical decision experiment and a meaning-definition task (e.g., What does squander mean?). Also as predicted, H.M.'s lexical decision performance declined dramatically between ages 57 and 71 for low-frequency words, but was age invariant for high-frequency words. PMID- 11760137 TI - Moving to directly cued locations abolishes spatial interference during bimanual actions. AB - Interference is frequently observed during bimanual movements if the two hands perform nonsymmetric actions. We examined the source of bimanual interference in two experiments in which we compared conditions involving symmetric movements with conditions in which the movements were of different amplitudes or different directions. The target movements were cued either symbolically by letters or directly by the onset of the target locations. With symbolic cues, reaction times were longer when the movements of the two hands were not symmetric. With direct cues, reaction times were the same for symmetric and nonsymmetric movements. These results indicate that directly cued actions can be programmed in parallel for the two hands. Our results challenge the hypothesis that the cost to initiate nonsymmetric movements is due to spatial intetference in a motor-programming stage. Rather the cost appears to be caused by stimulus identification, response selection processes connected to the processing of symbolic cues, or both. PMID- 11760138 TI - Unsupervised statistical learning of higher-order spatial structures from visual scenes. AB - Three experiments investigated the ability of human observers to extract the joint and conditional probabilities of shape co-occurrences during passive viewing of complex visual scenes. Results indicated that statistical learning of shape conjunctions was both rapid and automatic, as subjects were not instructed to attend to any particularfeatures of the displays. Moreover, in addition to single-shape frequency, subjects acquired in parallel several different higher order aspects of the statistical structure of the displays, including absolute shape-position relations in an array, shape-pair arrangements independent of position, and conditional probabilities of shape co-occurrences. Unsupervised learning of these higher-order statistics provides support for Barlow's theory of visual recognition, which posits that detecting "suspicious coincidences" of elements during recognition is a necessary prerequisite for efficient learning of new visual features. PMID- 11760139 TI - A cross-cultural analysis of avoidance (relative to approach) personal goals. AB - The results from this research supported our primary hypothesis that the adoption of avoidance (relative to approach) personal goals varies as a function of individualism-collectivism (across representations of this distinction). Interdependent self-construals were positively related and independent self construals were negatively related to adoption of avoidance goals (Study 1), Asian Americans adopted more avoidance goals than non-Asian Americans (Study 2), andpersonsfrom South Korea and Russia adopted more avoidance goals than those in the United States (Studies 3 and 4, respectively). Studies 3 and 4 investigated andfound supportfor our secondary hypothesis that avoidance personal goals are a negative predictor of subjective well-being in individualistic (the United States), but not collectivistic (South Korea and Russia), countries. The findings are discussed in terms of other approach-avoidance constructs and motivational processes. PMID- 11760140 TI - A dissociation between attention and selection. AB - It is widely assumed that the allocatian of spatial attention results in the "selection" of attended objects or regions of space. That is, once a stimulus is attended, all its feature dimensions are processed irrespective of their relevance to behavioral goals. This assumption is based in part on experiments showing significant interference for attended stimuli when the response to an irrelevant dimension conflicts with the response to the relevant dimension (e.g., the Stroop effect). Here we show that such interference is not due to attending per se. In two spatial cuing experiments, we found that it was possible to restrict processing of attended stimuli to task-relevant dimensions. This new evidence supports two novel conclusions: (a) Selection involves more than the focusing of attention per se: and (b) task expectations play a key role in detertnining the depth of processing of the elementary feature dimensions of attended stimuli. PMID- 11760141 TI - Explaining math: gesturing lightens the load. AB - Why is it that people cannot keep their hands still when they talk? One reason may be that gesturing actually lightens cognitive load while a person is thinking of what to say. We asked adults and children to remember a list of letters or words while explaining how they solved a math problem. Both groups remembered significantly more items when they gestured during their math explanations than when they did not gesture. Gesturing appeared to save the speakers' cognitive resources on the explanation task, permitting the speakers to allocate more resources to the memory task. It is widely accepted that gesturing reflects a speaker's cognitive state, but our observations suggest that, by reducing cognitive load, gesturing may also play a role in shaping that state. PMID- 11760142 TI - The integration of body movement and attention in young infants. AB - The normal development of adaptive behavior in humans depends on the integration of visual attention and body movement, yet little is known about the initial state of movement-attention coupling at the beginning of postnatal life. We studied 1- and 3-month-old infants during extended periods of visual exploration and found that spontaneous shifts of gaze are preceded by rapid changes in general body movement. The results reveal a tight link between motor activation and overt attention on a time scale of seconds or less. This link undergoes substantial developmental change in the first few weeks after birth. During that time, phasic motor activation may play a key role in visual exploration by helping to unlock gaze when the environment is unchanging. PMID- 11760143 TI - Alcohol affects emotion through cognition. AB - Determining how, cognition and emotion interact is pivotal to an understanding of human behavior and its disorders. Available data suggest that changes in emotional reactivity and behavior associated with drinking are intertwined with alcohol's effects on cognitive processing. In the study reported here, we demonstrated that alcohol dampens anticipatory fear and response inhibition in human participants not by directly suppressing subcortical emotion centers, as posited by traditional tension-reduction theories, but instead by impairing cognitive-processing capacity. During intoxication, reductions in fear response (assessed via startle potentiation) occurred only under dual-stimulus conditions, and coincided with reduced attentional processing of threat cues as evidenced by brain response (assessed via P3 event-related potentials). The results are consistent with higher cortical mediation of alcohol 's effects on fear, and illustrate more broadly how disruption of a cognitive process can lead to alterations in emotional reactivity and adaptive behavior. PMID- 11760144 TI - Sensorimotor adaptation to violations of temporal contiguity. AB - Most events are processed by a number of neural pathways. These pathways often differ considerably in processing speed. Thus, coherent perception requires some form of synchronization mechanism. Moreover, this mechanism must be flexible, because neural processing speed changes over the life of an organism. Here we provide behavioral evidence that humans can adapt to a new intersensory temporal relationship (which was artificially produced by delaying visual feedback). The conflict between these results and previous work that failed to find such improvements can be explained by considering the present results as a form of sensorimotor adaptation. PMID- 11760145 TI - Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. AB - The stromal cell population in bone marrow has been the focus of much attention since it has been shown that this cell population can be expanded and differentiated into cells with the phenotype of bone, cartilage, muscle, stroma, neural, and fat cells. We evaluated umbilical cord blood (UCB) for the presence of these cells. From the mononuclear fraction of UCB, we demonstrated the presence of a subset of cells that have been maintained in continuous culture for more than 6 months (>10 passages). These adherent cell populations express adhesion molecules CD13+, CD29+, and CD44+, but not antigens of hematopoietic differentiation. Exposure of these cells to osteogenic agents resulted in an increase in expression of alkaline phosphatase and the appearance of hydroxyapatite nodules by Von Kossa staining. Incubation with adipogenic agents resulted in morphological change and staining with Oil Red O. In addition, when exposed to basic fibroblast growth factor and human epidermal growth factor the cells underwent changes consistent with cells of neural origin. These changes were demonstrated by a combination of immunofluorescent labeling and Western immunoblots for neural-specific markers. Thus, similar to what has been previously reported with bone marrow, cord blood contains a population of cells that can be expanded in culture and are able to express the phenotype of multiple lineages. Cord blood multilineage cells are slower to establish in culture, have a lower precursor frequency and a lower level of bone antigen expression, and lack constitutive expression of neural antigens when compared to bone marrow, suggesting a more primitive population. Cord blood may prove to be a new source of cells for cellular therapeutics for stromal, bone, and, potentially, neural repair. PMID- 11760146 TI - Donor natural killer (NK1.1+) cells do not play a role in the suppression of GVHD or in the mediation of GVL reactions after DLI. AB - Donor regulatory T cells (CD3+ alphabetaT-cell receptor [TCR]+) derived from the repopulating host thymus have been shown to be primarily responsible for suppression of GVHD following DLI therapy in murine BMT models. However, natural killer (NK) T cells also have regulatory properties, and a role for NK T cells in suppression of GVH reactivity has not been completely excluded. NK cells may also contribute to the graft-versus-leukemia (GVL) effect associated with DLI therapy. In this study, we used a murine BMT model (C57BL/6 into AKR) to study whether depletion of donor NK cells had any impact on the suppression of GVH reactivity after DLI or on the DLI-induced GVL effect against acute T-cell leukemia. Depletion of donor NK cells was accomplished in vivo by giving DLI-treated bone marrow chimeras multiple injections of anti-NK1.1 monoclonal antibody (MoAb). The chimeras treated with anti-NK1.1 MoAb had significantly fewer splenic NK1.1 cells than nontreated chimeras, and splenocytes from anti-NK1.1-treated mice were deficient in the ability to generate lymphokine-activated lytic activity. Results presented here showed that NK-cell depletion had no effect on the suppression of GVH reactivity after DLI. When DLI-treated chimeras were challenged with an acute T-cell leukemia, NK-cell depletion had no discernible effect on GVL reactivity. These preclinical data suggest that donor NK cells do not have a significant role in the suppression of GVHD after DLI or in the mediation of GVL reactivity induced by DLI. PMID- 11760147 TI - Double-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation. AB - The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown. We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation. One hundred two patients were randomized to receive either 8 mg PO ondansetron every 8 hours, 1 mg PO granisetron every 12 hours, or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens. Study arms were compared in terms of emetic episodes, subjective nausea, amount and cost of rescue antiemetics used, and total costs. Response was defined as complete response (CR), no emesis with no or mild nausea and no rescue antiemetics; major response (MR), 1 episode of emesis or moderate nausea with or without rescue antiemetics; and major efficacy (ME), CR + MR. Subjective nausea was assessed using a 100-mm visual analog scale (VAS) with 0 = no nausea. Ninety-six patients completed the study; the trial was analyzed according to intention-to-treat. Overall CR rates were: 48% for oral ondansetron, 47% for oral granisetron, and 49% for IV ondansetron. Overall ME rates were 82% for oral ondansetron, 84% for oral granisetron, and 81% for IV ondansetron. Mean VAS scores were 32 for oral ondansetron, 32 for oral granisetron, and 27 for IV ondansetron. None of the differences were statistically significant. A cost analysis revealed significant differences among all arms (P = .0001, all comparisons). All 3 regimens had similar efficacy in this BMT population; oral ondansetron was the most cost effective. PMID- 11760148 TI - Successful allogeneic stem cell transplantation with nonmyeloablative conditioning in patients with relapsed hematologic malignancy following autologous stem cell transplantation. AB - The use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancy after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We evaluated the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in 13 patients (median age, 38 years) with relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphoma, n = 6; multiple myeloma, n = 2) after initial autoSCT. Median time from autoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemotherapy refractory disease following autoSCT, 6 were in untreated relapse, and 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal irradiation); and a very short course of cyclosporine as GVHD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who had no evidence of GVHD, received prophylactic DLI beginning 5 to 6 weeks after transplantation for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft versus-tumor effect. Six patients showed conversion to full donor chimerism and 1 lost the graft. Grade II or greater acute GVHD occurred in 9 patients. Seven patients achieved a complete response; 6 had no response. The median survival time of the 13 patients is currently 10 months (range, 3-39 months), with an overall survival probability at 2 years of 45% (95% confidence interval [CI], 19% 73%) and a disease-free survival probability at 2 years of 37.5% (95% CI, 12% 65%). Thus, this novel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients with advanced hematologic malignancies after a failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in the treatment of hematologic malignancies after an autologous transplantation. PMID- 11760149 TI - G-CSF-mobilized peripheral blood mononuclear cells added to marrow facilitates engraftment in nonmyeloablated canine recipients: CD3 cells are required. AB - Stable mixed donor/host hematopoietic chimerism can be uniformly established in dogs conditioned with 200 cGy TBI before dog leukocyte antigen (DLA)-identical marrow transplantation and immunosuppressed with a short course of mycophenolate mofetil (MMF) and cyclosporine (CSP) after the transplantation. A further decrease in the TBI dose to 100 cGy or the elimination of MMF in this model results in graft rejection. Here we asked whetherthe addition of G-CSF-mobilized peripheral blood mononuclear cells (G-PBMC) to marrow grafts would enhance donor engraftment in dogs conditioned with 100 cGy TBI and given postgrafting immunosuppression with CSP alone. Using this model, 7 of 9 dogs given only marrow cells rejected their grafts within 8 to 17 weeks after transplantation. In contrast, the addition of unmodified G-PBMC to marrow grafts resulted in stable mixed donor/host chimerism in 5 of 8 dogs studied (P = .06). However, addition of the CD3-depleted fraction of G-PBMC, which contained both CD34 cells and CD14 cells, resulted in engraftment in only 1 of 7 recipients. We conclude that adding G-PBMC to marrow grafts replaced the requirement of MMF and 100 cGy of TBI, and that CD3 cells were required to facilitate engraftment of marrow cells in DLA identical recipients, whereas the additional CD34 cells present in G-PBMC were not sufficient for this effect. PMID- 11760150 TI - Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T cell depletion. AB - Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors. PMID- 11760151 TI - Examination of dietary methylmercury exposure in the Casa Pia Study of the health effects of dental amalgams in children. AB - This study examined methylmercury concentrations in blood of children participating in the Casa Pia Study of the Health Effects of Dental Amalgams in Children over a 1-yr period and related them to their diets in terms of fish and other seafood consumption. One hundred and fifty children between the ages of 8 and 10 yr who were residents of the Casa Pia School System of Lisbon, Portugal, participated. Parents or caregivers completed a food frequency questionnaire designed specifically for this study at baseline. Children provided urinary and blood samples for mercury determinations at baseline and at 1 yr following placement of dental tooth fillings. Mercury levels in fish samples from children's diets were also obtained. Mercury determinations in urine, blood, and fish were performed using cold vapor atomic fluorescence spectroscopy. The mean value of baseline methylmercury concentrations in blood increased as the report of seafood consumption increased, although not statistically significantly. However, blood methylmercury and total mercury concentrations were significantly lower at 1-yr follow-up than at baseline. Sixty-one percent of parents/caregivers reported that their children consumed fish on a weekly basis. The fish offered at a sample of the schools contained low levels of methylmercury (range 13.9-23.6 ng/g). Thus, children participating in the Casa Pia dental amalgam study are exposed to low dietary levels of methylmercury by way of fish consumption, and this finding was reflected in the low mean blood methylmercury concentrations observed. The present findings indicate that dietary methylmercury is not a significant source of mercury exposure and is not likely to confound the association of dental amalgam mercury with potential health effects in the present study. PMID- 11760152 TI - Differences in oxidative stress between young Canada geese and mallards exposed to lead-contaminated sediment. AB - Lead (Pb) exposure results in an increase in tissue lipid peroxides and variation in glutathione (GSH) concentrations, which can be related to peroxidative damage of cell membranes in Pb-poisoned animals. Species and individual variation in sensitivity to Pb poisoning among animals may be due to differential resistance to oxidative stress. The effects of oxidative stress caused by Pb exposure (1.7, 414, and 828 microg/g of diet) were compared for the first 6 wk in growing young of two species of waterfowl, Canada geese (Branta canadensis) and mallards (Anas platyrhynchos), with the first species being possibly more sensitive to Pb poisoning based on previous field and laboratory observations. Blood and liver Pb concentrations increased more in mallards than in geese. This may be explained on the basis of body weight, being 3.2 times higher in geese, and by hepatic metabolism, where GSH S-transferase (GST) activity is 2.9-fold higher in geese and presumably has a role in the binding of Pb to GSH and subsequent biliary excretion. In contrast, mallards showed higher hepatic levels of GSH and activities of CSH peroxidase (GPX) and GSH reductase (GR). Although both species showed a rise in hepatic GSH concentration with Pb exposure, the relationship between increased lipid peroxidation and Pb exposure was only significant in geese. Within treatment groups, hepatic GSH concentrations were inversely related to liver Pb concentrations in both species, which may correspond to the role of GSH in Pb excretion. Hepatic GSH was also inversely related to hepatic lipid peroxidation, but only in mallards and in agreement with the species differences observed in GPX and GR activities. The lower resistance to lipid peroxidation of Canada geese may explain why geese can die in the field from Pb poisoning after ingesting fewer shot than found in the gizzards of mallards and with lower liver Pb concentrations than in mallards. PMID- 11760153 TI - Inflammatory cell availability affects ozone-induced lung damage. AB - Identifying whether or not neutrophils have a role to play in the early stages of acute lung epithelial injury brought about by inhalation of reactive substances continues to be a major area of investigation. In this study, the availability of circulating neutrophils was manipulated by treatment with either cyclophosphamide or rabbit antiserum against rat neutrophils, prior to exposures to air, a single high ozone exposure of 1 or 2 ppm for 3 h, or a continuous exposure to 0.8-1.0 ppm for up to 48 h. Although cyclophosphamide treatment resulted in undetectable levels of neutrophils in the blood, the recovery of tissue marginated interstitial neutrophils of 1 x 10(6) cells by collagenase tissue digestion was not significantly diminished at the onset of air and ozone exposures. Cyclophosphamide treatment alone did not cause any permeability damage to air exposed rat lungs, but did ameliorate ozone-induced increases in bronchoalveolar lavage (BAL) neutrophil and albumin recoveries after both short-term and 1 d of continuous ozone exposure. In contrast to cyclophosphamide, antiserum treatment resulted in greater than a 90% decrease in neutrophil recoveries from both blood and lung tissue at the onset of air and ozone exposures. Antiserum treatment also abrogated ozone-induced neutrophil accumulations in lung lavageable spaces following both single and continuous ozone exposures, but did not significantly affect ozone-associated lung permeability damage indicated by unaltered BAL fluid albumin recoveries. These data demonstrated that under experimental conditions when neutrophils remain within lung tissue marginated and interstitial pools, reduction in circulating blood neutrophil availability is associated with a concomitant decrease in ozone-induced lung damage. PMID- 11760154 TI - Exposure to flaxseed or its purified lignan during suckling only or continuously does not alter reproductive indices in male and female offspring. AB - Based on the reported health benefits of flaxseed, many Canadians are choosing to consume flaxseed or flaxseed-containing foods. However, the safety of exposure to flaxseed during early life such as the suckling period has not been studied, despite the fact that components in flaxseed with potential hormone-like effects can be transferred to nursing offspring via mother's milk. Previous investigations demonstrated that maternal feeding of a 10% flaxseed diet during pregnancy and lactation resulted in estrogenic effects on reproductive indices among male and female offspring. These effects were attributed to the potential estrogenic activity of enterodiol and enterolactone, the two major mammalian lignans that are converted from secoisolariciresinol diglycoside (SDG) in flaxseed by colonic bacteria; however, the effect of exposure to purified SDG at the level of a 10% flaxseed diet was not studied. The objective of this study was to determine whether maternal feeding of flaxseed during lactation altered reproductive indices in male and female offspring. Rat dams were fed basal diet (BD) or BD containing either 100% flaxseed (10F) or the equivalent quantity of SDG present in the 10% (10S) flaxseed diet from the start of lactation until pups were 21 d old. At the end of lactation (postnatal day IPND] 21), suckling pups either continued on the mother's diet or were switched to BD until adolescence (PND 50) or young adulthood (PND 132) to determine if continuous exposure to flaxseed or SDG altered reproductive indices. The reproductive indices that were measured included anogenital distance from birth through PND 21, age and body weight at puberty onset (females only), estrous cycle length, reproductive organ weights at PND 50 and 132, and histological analysis of reproductive organs (uterus, ovaries, prostate) at PND 132. There were no significant effects of exposing male or female offspring to flaxseed or SDG during suckling only or during suckling through the postsuckling period on any of the reproductive indices measured. These findings are in contrast to the estrogenic effects observed in male and female offspring exposed to flaxseed during fetal life through suckling and suggest that fetal life is a more hormone-sensitive period of development. Although maternal feeding of flaxseed during lactation appears to be safe with respect to reproductive indices among offspring, future investigation is required to elucidate whether there are any long-term implications with respect to fertility. PMID- 11760155 TI - Metabolism of territrem a by liver microsomes of Wistar rats: identification of the metabolites and their metabolic sequence. AB - The metabolism of territrem A (TRA) was investigated in liver microsomes of male Wistar rats. The results indicated that three metabolites were produced from TRA and these metabolic reactions were inhibited by metyrapone, an inhibitor of cytochrome P-450. Based on analysis by high-performance liquid chromatography (HPLC), mass, and nuclear magnetic resonance (NMR) spectroscopic techniques, the structure of these metabolites were identified as 4beta-hydroxymethyl-4beta demethylterritrem A (MA1), 4beta-oxo-4beta-demethylterritrem A (MAX), and 2 dihydro-4beta-demethylterritrem A (MA2). It was proposed that reactions proceeded by three sequential oxidative reactions in the pyran moiety of TRA: first, hydroxylation at the 4beta-C methyl group of TRA to form MA1; second, oxidation at the 4beta hydroxyl group of MA, to form MAX; and third, decarbonylation at the 4beta-C oxo group of MAX to form MA2. PMID- 11760156 TI - Vancomycin-resistant enterococci in neonates. AB - Fecal-oral transmission of vancomycin-resistant strains of Enterococci (VRE), which colonize the human gastrointestinal tract, has led to nosocomial epidemics in recent years. The aim of this study was to establish the incidence and associated factors of fecal colonization with VRE in neonates. In our hospital 110 rectal swab specimens collected in the neonatal intensive care unit (NICU) were examined for VRE. For comparison, rectal swabs collected from 42 healthy neonates on the obstetrics ward were also analyzed. Of the NICU patients, 8 had VRE MICs of 8-64 microg/ml for vancomycin and 2-32 microg/ml for teicoplanin, whereas none of the healthy newborns, had VRE (p < 0.05). All patients positive for VRE had factors known to be associated with VRE carriage, such as low birth weight or long-term antibiotic therapy. PMID- 11760157 TI - Antibodies and T-cell reactivity to Borrelia burgdorferi in an asymptomatic population: a study of healthy blood donors in an inland town district in the south-east of Sweden. AB - To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-gamma ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection. PMID- 11760158 TI - Avidity determination of Borrelia burgdorferi-specific IgG antibodies in Lyme disease. AB - The avidity indices of Borrelia burgdorferi-specific IgG antibodies were estimated using ELISA in sera from patients with different stages of Lyme disease. In addition, sera from healthy students with proof of borrelial-specific IgG antibodies from standard serology were tested. Low avidity indices were detected predominantly in sera from patients with early-stage Lyme disease [erythema migrans (EM); n = 25]. High avidity indices were found in healthy students (n = 72) and in most of the patients with neuroborreliosis (NB; n = 44) and chronic late-stage Lyme disease [acrodermatitis chronica atrophicans (ACA); n = 36]. In conclusion, early-stage Lyme disease (EM) could be differentiated from advanced and chronic stages (NB, ACA) and from "seropositive" healthy persons using avidity determination in the majority of patients in this study. PMID- 11760159 TI - Emergence of trimethoprim-resistant Escherichia coli in healthy persons in the absence of prophylactic or therapeutic antibiotics during travel to Guadalajara, Mexico. AB - Thirty-nine healthy US students without diarrheal disease and who had not received prophylactic or therapeutic antibiotics were monitored for emergence of trimethoprim-resistant gram-negative fecal flora for a 3-week period after arrival in Guadalajara, Mexico. During this time period, most students showed no change in total fecal gram-negative bacteria (p > 0.05) but showed an increasing level of trimethoprim (TMP) resistance (p < 0.01) among fecal coliforms. Escherichia coli was the TMP-resistant organism isolated in 18 of 39 (46%) healthy students. These 18 TMP-resistant E. coli were also resistant to ampicillin (44%), azithromycin (11%), chloramphenicol (39%), ciprofloxacin (11%), doxycycline (89%), erythromycin (100%), furazolidone (72%), levofloxacin (17%), trimethoprim-sulfamethoxazole (89%) and trovafloxacin (17%). In the absence of prophylactic and therapeutic antibiotics, increased acquisition of TMP-resistant gram-negative fecal flora in this developing country is probably due to poor sanitary conditions and the recurrent and heavy exposure to antimicrobial resistant indigenous flora as a result of contaminated food and drink. PMID- 11760160 TI - Dental caries is common in Finnish children infected with Helicobacter pylori. AB - Childhood factors such as low socioeconomic status are risk factors for Helicobacter pylori infection and Streptococcus mutans-related dental caries. We examined whether H. pylori infection and dental caries are present today in the same group of children examined previously. We reviewed the public dental health service files of 21 H. pylori-positive children (upper gastrointestinal endoscopy at a median age of 13.5 y) and 27 H. pylori-negative children (endoscopy at a median age of 12.5 y) examined during 1995-98 at the Helsinki University Central Hospital, Finland. All H. pylori-positive children had experienced dental caries in their primary or permanent teeth or in both whereas among H. pylori-negative children the respective proportion was 70% (p < 0.01). At the age of 7 y, 18% (3/17) of the H. pylori-positive children had experienced caries in permanent teeth as compared to 0% among H. pylori-negative children (0/24; p < 0.05). At the age of 12 y, H. pylori-positive children had more decayed, missing or filled permanent teeth than H. pylori-negative children (80% vs. 38%; p < 0.05). Although a causal relationship between H. pylori and dental caries is unlikely, it is possible that H. pylori-infected children have an increased risk of other health problems, such as dental caries, for which proper treatment is needed. PMID- 11760161 TI - Investigation of synergism of meropenem and ciprofloxacin against Pseudomonas aeruginosa and Acinetobacter strains isolated from intensive care unit infections. AB - The aim of this study was to determine synergistic effects of meropenem and ciprofloxacin against Pseudomonas aeruginosa and Acinetobacter strains isolated from intensive care unit (ICU) infections. A total of 18 P. aeruginosa and 17 Acinetobacter strains were tested. MICs were determined using the broth microdilution method. The synergy of meropenem and ciprofloxacin was investigated in glass tubes using time-kill methodology. The synergistic effect of meropenem and ciprofloxacin in combination was found to be 22% at 0.5 x the MIC and 61% at 1 x the MIC in P. aeruginosa strains. Two strains (11%) showed synergy at both 0.5 and 1 x the MIC. Of the 18 P. aeruginosa strains, 1 strain (6%) did not show a synergistic effect at either 0.5 or 1 x the MIC. In Acinetobacter strains, the synergistic effect of meropenem and ciprofloxacin in combination was found to be 29% at 0.5 x the MIC and 18% at 1 x the MIC. One strain (6%) showed synergy at both 0.5 and 1 x the MIC. Of the 17 Acinetobacter strains, 8 strains (47%) did not show a synergistic effect at either 0.5 or 1 x the MIC. According to the results of this study, the combination of meropenem and ciprofloxacin is more effective than either antibiotic alone in ICU infections due to P. aeruginosa strains. PMID- 11760162 TI - Rate of carriage of Serratia marcescens in patients with and without evidence of infection. AB - The epidemiology of Serratia marcescens is poorly understood. We designed a study to investigate carriage sites of the organism, and possible modes of transmission of infection. Using Sorbitol-MacConkey agar with colistin 200 IU/ml and MacConkey agar with a 10 microg colistin disc we performed cultures from various sites in patients already infected with S. marcescens. Over the same period of time we also investigated all patients in the intensive care unit (ICU) for colonization with the agent. Environmental screening was performed in the ICU only. Of 37 infected patients, 65% demonstrated carriage at a second site and 43% at multiple sites. Throat carriage was found in 59%, faecal carriage in 42%, nasal carriage in 31% and urinary carriage in 22%. Carriage over several weeks was found in 22%. Of 40 ICU patients, 10% demonstrated nasal and/or throat carriage. Environmental screening yielded 4 isolates. All ICU patient strains and a strain from the ICU bedpan macerator were O14:K14 with similar random amplified polymorphic DNA types. These results show that patients with S. marcescens infection are likely to carry the organism at multiple sites and that carriage may be prolonged. A significant level of carriage was also found in non-infected patients in a unit where the organism was prevalent. PMID- 11760163 TI - Comparison of cefepime and ceftazidime in combination with amikacin in the empirical treatment of high-risk patients with febrile neutropenia: a prospective, randomized, multicenter study. AB - A total of 208 adult patients with cancer and febrile neutropenia from 5 medical institutions were randomized to receive either cefepime (2 g b.i.d.) or ceftazidime (2 g t.i.d.) in combination with amikacin (15 mg/kg/o.d.). Ninety seven patients in the ceftazidime (CEZ) group and 98 in the cefepime group (CEF) were evaluable for efficacy. In 68 patients (35%), infection could be documented. The average duration of antibiotic therapy was 11 and 12 d and response rates to the empirical regimen were 36 and 30% for the CEZ and CEF groups, respectively (p > 0.05). The average time of defervescence in responders was 3 d for both groups. Modification of the initial regimen with antivirals and/or azole antifungals raised the number of responders to 44% and 35%, respectively (p > 0.05). Vancomycin was additionally given to 29 patients in the CEZ group and to 27 patients in the CEF group. Twenty-six patients in each group received empirical amphotericin B. Mild, reversible study drug-related side-effects were observed in 12 patients (12%) in the CEZ group and 13 patients (13%) in the CEF group (p > 0.05). Cefepime in combination with amikacin seems to be as effective, safe and tolerable as ceftazidime + amikacin in patients with high-risk neutropenia and fever. PMID- 11760164 TI - A prospective, randomized, multicenter comparative study of clinafloxacin versus a ceftriaxone-based regimen in the treatment of hospitalized patients with community-acquired pneumonia. AB - In an open-label, phase 3, randomized, multicenter study, clinafloxacin (200 mg/d) was compared to ceftriaxone (2 g/d; with or without erythromycin) in 527 patients with acute community-acquired bacterial pneumonia (CAP). Primary efficacy parameters were clinical cure rate and microbiologic eradication rates (by pathogen and by patient) determined 5-9 d post-therapy (test of cure; TOC). Clinical cure rates at TOC for the 2 treatment groups were equivalent in the intention-to-treat (clinafloxacin 79.3, ceftriaxone 78.6%), clinically evaluable (clinafloxacin 88.1, ceftriaxone 85.0%), modified intention-to-treat (clinafloxacin 82.6, ceftriaxone 86.9%) and microbiologically evaluable populations (clinafloxacin 86.2, ceftriaxone 86.2%). Microbiologic eradication rates were similar in the 2 treatment groups. Both drugs were tolerated. Treatment of hospitalized CAP patients with clinafloxacin is a reasonable choice, especially when a resistant pathogen is anticipated. PMID- 11760166 TI - Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers. AB - This study assessed tick-borne encephalitis virus (TBEV) neutralizing antibody levels after injection of FSME-BULIN S/D (human tick-borne encephalitis immunoglobulin; 0.2 ml/kg body weight) in healthy volunteers. After screening of 18 volunteers for TBEV antibody titers, 12 healthy volunteers with TBEV antibody titers < 5 were entered into the pharmacokinetic part of the study. TBEV antibody titers were analyzed before injection and after 24 h, 48 h, 3 d, 4 d and 8 d. Vital signs, adverse events and laboratory tests for safety were analyzed after intramuscular injection with the immunoglobulin at 4 sites in the gluteal muscles. Injection with 0.2 ml/kg of FSME-BULIN S/D induced a fast increase in, and sustained titers of, neutralizing antibody levels against TBEV. The injections were well tolerated and the safety profile of the product was fully acceptable. PMID- 11760165 TI - Hepatitis C virus kinetics during induction and standard 3 times a week interferon-alpha therapy. AB - We studied HCV kinetics during the first 84 d of interferon-alpha (IFN) treatment. IFN was administered either at a dose of 3 million units daily for the first 14 d and thereafter 3 times per week (t.i.w.) (induction treatment), or at a dose of 3 million units t.i.w. throughout (standard treatment). No patient had received HCV treatment previously, and all had a pretreatment viral load of < 1.2 x 10(6) IU/ml at screening. Ten patients were given induction treatment and 21 received the standard t.i.w. regimen. Twenty patients were infected with genotype 1. At Day 2, the median HCV RNA level in the induction group was significantly lower compared to that of the standard treatment group. This significant difference persisted during the study period for patients infected with genotype 1, but was not maintained from Day 14 onwards for patients with genotype non-1. At Day 84, 80% (8/10) of patients in the induction group, compared to 16% (3/19) in the standard treatment group, had undetectable (< 600 IU/ml) HCV RNA levels (p < 0.05). We conclude that induction treatment resulted in a significantly greater decline in HCV RNA levels than standard treatment. PMID- 11760167 TI - Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children. AB - During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time. PMID- 11760168 TI - Fever of unknown origin in uremic patients: a controlled prospective study. AB - Twenty-nine uremic patients with fever of unknown origin (FUO) admitted to our clinic between 1994 and 1998 were evaluated prospectively. A group of 50 consecutive non-uremic patients with FUO followed up during the same period was used for comparison. The causes of FUO found in the uremic and non-uremic groups, respectively were as follows: infectious diseases, 69 vs. 44% (p = 0.03); collagen vascular diseases, 6.9 vs. 6%; neoplasms, 3.4 vs. 26%; miscellaneous causes, 3.4 vs. 16%; and undiagnosed, 17.2 vs. 8%. Tuberculosis was the most common cause of FUO in both groups. The spectrum of underlying conditions for FUO in our uremic patients differed from that in the non-uremic patients and the uremic patients had a very high propensity for infectious diseases, especially tuberculosis. PMID- 11760169 TI - Non-tropical thoraco-abdominal pyomyositis caused by group A streptococcus in an immunocompetent adult. AB - We present a case of group A streptococcal pyomyositis of the thoraco-abdominal wall of an immunocompetent adult. This diagnosis was made when soft tissue swelling was seen on chest X-ray. Complete recovery followed drainage of the collection and short-course i.v. penicillin. The importance, diagnosis and treatment of pyomyositis are outlined. PMID- 11760170 TI - Multilocalized pyomyositis in a previously healthy subject. AB - A case of pyomyositis is presented. This case is unique in the literature as at least 29 abscesses were detected, affecting the vast majority of big muscle groups. We outline the origin of this disease entity which selectively affects striated muscles. We also discuss its natural history and management strategy. PMID- 11760171 TI - Transfusion-mediated Yersinia enterocolitica septicemia in an adult patient with beta-thalassemia. AB - We report a case of transfusion-mediated Yersinia enterocolitica septicemia in a 43-y-old woman with homozygous beta-thalassemia. Two h after transfusion of 3 units of red blood cells the patient suffered high-grade fever and shaking chills. Y. enterocolitica serotype O3 grew in blood cultures. Prolonged treatment with i.v. ceftriaxone plus ciprofloxacin led to a favorable outcome. Transfusion associated Y. enterocolitica septicemia has not previously been reported in an adult beta-thalassemic patient from the Mediterranean area. Our report is particularly important, because of the high incidence of chronically transfused thalassemic patients in Mediterranean countries. PMID- 11760172 TI - Myocarditis in a patient with salmonella and campylobacter enteritis. AB - Myocarditis associated with bacterial enteritis has only rarely been described and the pathogenesis is unclear. Herein we report a case where a young adult developed myocarditis during the acute stage of an infection with Salmonella heidelberg and Campylobacter jejunii/coli. The patient's troponin I value was elevated. We suggest that use of cardiac-sensitive troponins may be a useful tool for diagnosis of acute myocarditis in the context of bacterial enteritis. We also suggest the need for further investigation of the pathogenesis of myocarditis associated with enteric pathogens. PMID- 11760173 TI - Invasive Salmonella virchow infection in childhood. AB - Salmonella virchow is generally considered to be one of the less invasive non typhoidal Salmonellae species; however, several invasive cases have previously been reported. We report 3 cases of otherwise healthy children with S. virchow bacteraemia, monoarthritis and prevertebral abscess, only 1 of whom had previously had gastroenteritis. All 3 children responded to antibiotic regimens consisting of cefotaxime for 10 d, ceftriaxone for 3 weeks and ceftriaxone plus clindamycin for 4 weeks, respectively. In conclusion, S. virchow may be a more invasive serotype in immunocompetent children and present with a wider spectrum of manifestations than considered previously. PMID- 11760174 TI - Splenic granulomatous lesions in immunocompetent pediatric patients with visceral leishmaniasis. AB - Visceral focal lesions are rarely encountered in patients with leishmaniasis despite the fact that splenomegaly, and to a lesser extent hepatomegaly, predominate among the clinical features of the disease. We present, using high resolution ultrasonography, the first 3 reported cases of focal splenic involvement in immunocompetent children with visceral leishmaniasis. All patients showed a prompt response to the conventional anti-leishmanial treatment administered. This favorable outcome indicates that localized splenic lesions should not be considered as a poor prognostic factor and that alteration of the standard anti-leishmanial regimens is not justified. PMID- 11760175 TI - Tuberculoma of the cavernous sinus. AB - A case of tuberculoma of the cavernous sinus is described and 4 other previously reported cases are reviewed. The condition is very rare, and predominantly affects Asians. Periorbital pain, ptosis and ophthalmoplegia are the most common presenting features. Clinical and radiological findings are not sufficiently sensitive to differentiate it from other diseases affecting the cavernous sinus. Treatment is primarily medical, with antituberculous drugs, and the outcome is good. Surgery has a limited role in the management of this condition, mainly for establishing the diagnosis. PMID- 11760176 TI - Subcutaneous rupture of hepatic hydatid cyst. AB - Hepatic hydatid cysts are common entities. We present an unusual case of a hepatic hydatid cyst which had ruptured into the subcutaneous tissues of the anterior abdominal wall. The possible causes, imaging features and recent literature are reviewed. PMID- 11760177 TI - Spontaneous rupture of the spleen as presenting event in infectious mononucleosis. AB - We report the case of a patient who underwent a life-saving splenectomy after spontaneous rupture of the spleen. The patient had no history of recent trauma and developed obvious clinical signs of infectious mononucleosis only 5 d after the splenectomy. Also of note was the late seroconversion in this patient. PMID- 11760178 TI - Spontaneous splenic rupture associated with CMV infection: report of a case and review. AB - The case of a 43-y-old healthy woman presenting with spontaneous splenic rupture is reported. The outcome was favourable after splenectomy. Although the diagnosis of CMV infection was established by serology, PCR and immunostaining, no viral inclusions were observed on spleen sections. The pathophysiology of the lesions was unclear given the multiple interactions of the virus with various cell populations, and particularly with the immune system. PMID- 11760180 TI - Introduction to the special issue of Marine Pollution Bulletin: selected papers from the fourth International Marine Environmental Modelling Seminar, Athens, Greece, October 2000. PMID- 11760179 TI - Myocarditis associated with Campylobacter infection. AB - We describe the case of a young man with fever, chest pain and enteric symptoms. He developed myocarditis and Campylobacter was isolated in faeces. PMID- 11760181 TI - A numerical simulation of the seasonal cycle of temperature, salinity and velocity fields in Tokyo Bay. AB - To understand when oxygen-depleted waters occur, how they develop and when they dissipate in inner Tokyo Bay, realistic simulations were attempted with fine spatial and temporal resolution by applying realistic time dependent external forcing. A 3D hydrodynamic model was driven by time-dependent external forcing factors/parameters such as solar radiation, air temperature, relative humidity, wind velocity, and fluvial discharge, under the open boundary conditions of 1995. A simulated time series of salinity and temperature agreed fairly well with observed data, except in summer. The model failed to reproduce the development of the surface mixed layer in summer. Several sensitivity analyses on the external forcing parameters such as wind velocity and vertical diffusivity were conducted to reproduce the mixed layer. However, changing these parameter values did not improve the model results. PMID- 11760182 TI - Operational monitoring and forecasting in the Aegean Sea: system limitations and forecasting skill evaluation. AB - The POSEIDON system, based on a network of 11 oceanographic buoys and a system of atmospheric/oceanic models, provides real-time observations and forecasts of the marine environmental conditions in the Aegean Sea. The buoy network collects meteorological, sea state and upper-ocean physical and biochemical data. The efficiency and functionality of the various system components are being evaluated during the present pre-operational phase and discussed in this paper. The problem of bio-fouling on optical and chemical sensors is found to be a main limitation factor on the quality of data. Possible solutions to this problem as well as quality control methods that are being developed are also described. Finally, an evaluation of the numerical models is presented through the estimation of their forecasting skill for selected periods. PMID- 11760183 TI - A semi-evolutive partially local filter for data assimilation. AB - The singular evolutive extended Kalman (SEEK) filter has been proposed recently by Pham et al. (1997) for data assimilation into numerical oceanic models. This filter has been applied in different realistic ocean frameworks and has provided satisfactory results (Pham et al., 1997; Verron et al., 1998). However, the SEEK filter remains expensive in real operational assimilation. To reduce cost and obtain a better representativity, we introduce the idea 'local correction basis'. Such basis however cannot be made to evolve according to the model without destroying its locality property. Therefore we shall keep this basis fixed and we augment it by a few global basis vectors which evolve. The resulting semi evolutive partially local filter is much less costly to implement than the SEEK filter and yet can yield better results. In the first application, validation twin experiments are conducted in a realistic setting of the OPA model over the tropical Pacific Ocean. PMID- 11760184 TI - Assessing marine ecosystem response to nutrient inputs. AB - The response of the Pagasitikos Gulf to enrichment caused by run-off fertilizers and the development and evolution of harmful algal blooms is investigated through ecosystem modelling. A standard generic complex model has been developed to describe the ecosystem processes of Pagasitikos and has been validated with in situ data. Additionally external nutrient fluxes have been assimilated and incorporated into the ecosystem dynamics. The investigation of spatial effects due to nutrient enrichment is investigated along a North-South transect. When externally forced the model successfully assimilates the external river inputs producing nutrient and chlorophyll-a concentrations, which are in good agreement with the in situ data. The nutrient inputs result in a more stable ecosystem at the north part of the Gulf and in the development of eutrophic conditions. The changes in the ecosystem functioning with emphasis on the nutrient cycling, the increase of primary production, and the modes of operation are investigated and discussed. PMID- 11760185 TI - A new coastal marine ecosystem model study coupled with hydrodynamics and tidal flat ecosystem effect. AB - A new coastal marine ecosystem model was developed, which was composed of pelagic and benthic ecosystems, and was applied to Mikawa Bay, Japan. This model deals with variations of biochemical and physical interactions among dissolved oxygen and C-N-P species (composition formed out of carbon, nitrogen and phosphorus elements) so that it resolves the flux dynamics of carbon, nitrogen, phosphorus and oxygen elements. The physical and biochemical mechanism figured in this model is constructed for the purpose of simulating the estuarine lower trophic ecosystem, in areas where the sea was too deep for light to reach the sea-bottom. As a result of coupling the benthic with pelagic system, the effect of process of sedimentation and nutrient diffusion back to the pelagic system could be indicated. In addition, by implementing the tidal flat ecosystem model's calculation result, the integrated model can include the effect of water purification in tidal flats where the light can reach the sea-bottom, and where seaweed, sea grass and benthic algae exist. In this study, the model indicates that oxygen-depleted water exists at the sea-bottom especially in summer mainly caused by an increase of oxygen consumption in the benthic system and a decrease of the vertical mixing water process. Furthermore, by comparing the case--with the tidal flat ecosystem model and the case without it, the effect of water purification of tidal flat estuaries was indicated. From the viewpoint of a short time scale, the tidal flat has the potential to restrict red tide (rapid increase of phytoplankton), and from the viewpoint of a long time scale, it restricts the sedimentation of detritus. Restricting the sedimentation prevents oxygen-depleted water occurring in the coastal marine system of Mikawa Bay. PMID- 11760186 TI - Strategies for transforming fine scale knowledge to management usability. AB - Simulation tools used for management purposes should fulfill several conditions by being computationally fast, user-friendly, realistic, generic and reliable. These traits are often counteracting since they simultaneously demand for model complexity as well as simplicity. Here we develop a strategy to overcome this general problem of environmental modelling for management use. Major ingredients are model analysis and reduction as new core components of the modelling process. In detail, a set of combined methods is proposed. Within a large class of models the set allows for automatically exploring model behaviour and for aggregating fine scale process knowledge together with spatio temporal resolution. Applications to a huge aquatic European regional seas ecosystem model (ERSEM), a complex photosynthesis model (PGEN) as well as a simple diagenetic model are presented. The analysis and aggregation methods provide first steps towards a new generation of decision support tools able to cope with an increase in scientific knowledge as well as management demands. PMID- 11760187 TI - Assessment of management options in marine fisheries by qualitative modelling techniques. AB - An effective management of the rapidly dwindling marine fish resources is of great ecological, economic and social importance for the future. An over development of commercial fisheries has brought about a multitude of negative environmental impacts, such as an accelerated exploitation of stocks or a decrease of marine biodiversity, and furthermore, a profound structural change in fish industry. However, the main reason for the non-prosperous rationing of marine resources is the lack of knowledge about certain processes as well as the non-availability of adequate steering instruments. This paper addresses the lack of conceptualization in the case of uncertain knowledge. It proposes a model approach which can be used for weak but improved decision support under the premise of vague knowledge. The usage of qualitative differential equations illustrates general patterns of overcapitalization of fishing fleets. The extension of traditional model approaches by integration of additional socio economic phenomena in this context supplies deeper insights in the dynamics of a coupled economic and ecological system. The approach provides a set of characteristic system behaviours which can be fruitfully used for the development of future management tasks. PMID- 11760188 TI - A hybrid near-field/far-field thermal discharge model for coastal areas. AB - A hybrid technique has been used to simulate the dispersion of heat from surface discharges in coastal areas. Characteristics of the near field thermal dispersion are described by the CORMIX3 model. A two-dimensional harmonic finite element hydrodynamic model (TEA) and a Eulerian-Lagrangian transport model (ELA) are applied for the far-field computation. A Gaussian puff algorithm in ELA, which represents the near field plume as a series of patches, is used to link the two regimes. The computed results are compared to available field measurements. Very reasonable agreement is observed. PMID- 11760189 TI - A model for deepwater oil/gas blowouts. AB - When gas is released in deepwater, the high pressure and low temperature can convert the gases into hydrates, which are buoyant. As these hydrates travel upwards they will encounter regions of lower pressure and can decompose into free gas. The presence or absence of hydrates has a significant impact on the behaviour of the jet/plume due to the alteration of the buoyancy. The free gas may dissolve in water. This paper describes a computer model developed to simulate the behaviour of oil and gas released from deepwater locations in the ocean. The model integrates the hydrodynamics and thermodynamics of the jet/plume with kinetics and thermodynamics of hydrate formation/decomposition. Model formulation and comparison of results with laboratory data for hydrates is presented. Scenario simulations show the behaviour of oil/gas under different deepwater conditions. PMID- 11760190 TI - A model of PCB bioaccumulation in the sea bass food web from the Seine Estuary (eastern English Channel). AB - A bioaccumulation model was developed to simulate the PCB contamination in the sea bass food web from the Seine Estuary. The model relies upon a contaminant mass balance budget for each biological species. Biological processes determine the extent of bioaccumulation: respiration and feeding rates control the uptake of contaminants whereas excretion, spawning, and growth act on the chemicals removal. A step-by-step modelling approach was followed. A first version was a steady-state model validated for the bioaccumulation processes. In the second version seasonal variation was taken into account, and finally in the third version, the model was coupled with a population dynamics model to describe PCB contamination in each age class. PMID- 11760191 TI - Overview of US minerals management service activities in deepwater research. AB - The US Minerals Management Service (MMS) is responsible for safe and environmentally sound management of offshore oil and gas resources. In recent years, there has been a tremendous increase in both activities and plans for deepwater development of these resources in the Gulf of Mexico (GOM). As the industry meets the enormous technical challenges involved, there is a concomitant effort to assure environmental protection of deep-ocean and coastal resources. This paper will outline the research planning and program currently underway to assess impacts, identify potential problems, and discover more about unknown resources of the deep ocean. PMID- 11760192 TI - Development of a data visualization and analysis tool to study the particle dynamics in the coastal zone. AB - Developing a field experiment to study the different aspects of the marine system involves both the co-operation of research groups from distinct disciplines and the use of various meteorological and oceanographical sensors deployed simultaneously at different locations. The information obtained, stored in voluminous data sets and frequently in various formats, needs to be visualized and analysed in different ways to provide knowledge of the dynamics of the system examined. There is therefore need for tools to be able to: (i) access and retrieve data sets stored in various file formats, and (ii) to allow their visualization and analysis. In this work, a user-friendly visualization and analytical tool was developed for this purpose using the IDL (Interactive Data Language v.5.3). It allows the description, interpretation and analysis of the temporal and spatial variability of both scalar and vector variables. A description of the software is given and an application using data from the High Frequency Flux (HFF) experiment, part of the European MTP II-Mater research project, in the Gulf of Lions is presented. PMID- 11760194 TI - Primate retina imaging with polarization-sensitive optical coherence tomography. AB - Polarization-sensitive optical coherence tomography (PSOCT) is applied to determine the depth-resolved polarization state of light backreflected from the eye. The birefringence of the retinal nerve fiber layer (RNFL) was observed and measured from PSOCT images recorded postmortem in a Rhesus monkey. An image processing algorithm was developed to identify birefringent regions in acquired PSOCT retinal images and automatically determine the thickness of the RNFL. Values of the RNFL thickness determined from histology and PSOCT were compared. PSOCT may provide a new method to determine RNFL thickness and birefringence for glaucoma diagnostics. PMID- 11760193 TI - The Poseidon operational tool for the prediction of floating pollutant transport. AB - In this work the development and the application of an operational management tool for the Greek Seas is described. This tool consists of a three-dimensional floating pollutant prediction model coupled with a weather, a hydrodynamic and a wave model in order to track the movements and the spreading of the pollutants and indicate those coastal areas which might be affected. The tool is part of the Poseidon system which has been designed to provide real time data and forecasts for marine environmental conditions in the Greek Seas. In this paper, we present four case studies based on realistic scenarios that show the value of the application for long-term strategic planning and short-term decision making in oil spill accidents. PMID- 11760195 TI - Flashed stimuli and the suppression of flicker response from long-wavelength sensitive cones: integrating two separate approaches. AB - The selective suppression of flicker response from LWS cones has been investigated with two approaches. One approach has emphasized the use of light adaptation conditions, and the other has emphasized the use of dark-adaptation conditions. In both cases, stimuli are arranged to restrict or exceed the ability of adaptation processes to maintain an afferent flicker response, and long wavelength stimuli are used to overload spectrally opponent processes. By integrating these two approaches, this study shows that diverse manifestations of flicker response suppression can be closely related mechanistically. For instance, the steep flicker TVI slopes that resulted from superimposing temporally modulated (100% contrast) test stimuli on flashed backgrounds corresponded to the disappearance of flicker that resulted from increasing the time-averaged illuminance of temporally modulated stimuli (contrast x < 100%) that were flashed alone in an otherwise dark field. For the stimulus parameters of this study, flicker response suppression was more evident for small (19' diameter) than for large (1 degree diameter) stimuli. However, flicker response suppression was elicited reliably for both sizes by adding a spatially coincident short-wavelength stimulus to the interstimulus interval between presentations of the long-wavelength stimuli. By showing that temporal contrast can be treated as an independent variable for an important set of test/background stimulus combinations, the results of this study make it possible to investigate the means by which changes of contrast gain help to maintain flicker response as assessed in a conventional flicker TVI paradigm. The reduced degree of suppression for relatively large stimuli probably is related to the increased action of spatially extensive contrast gain-control processes. These contrast gain-control processes might not act independently of spectrally opponent processes. PMID- 11760196 TI - Face verification through tracking facial features. AB - We propose an algorithm for face verification through tracking facial features by using sequential importance sampling. Specifically, we first formulate tracking as a Bayesian inference problem and propose to use Markov chain Monte Carlo techniques for obtaining an empirical solution. A reparameterization is introduced under parametric motion assumption, which facilitates the empirical estimation and also allows verification to be addressed along with tracking. The facial features to be tracked are defined on a grid with Gabor attributes (jets). The motion of facial feature points is modeled as a global two-dimensional (2-D) affine transformation (accounting for head motion) plus a local deformation (accounting for residual motion that is due to inaccuracies in 2-D affine modeling and other factors such as facial expression). Motion of both types is processed simultaneously by the tracker: The global motion is estimated by importance sampling, and the residual motion is handled by incorporating local deformation into the measurement likelihood in computing the weight of a sample. Experiments with a real database of face image sequences are presented. PMID- 11760197 TI - Robust structure from motion estimation using inertial data. AB - The utility of using inertial data for the structure-from-motion (SfM) problem is addressed. We show how inertial data can be used for improved noise resistance, reduction of inherent ambiguities, and handling of mixed-domain sequences. We also show that the number of feature points needed for accurate and robust SfM estimation can be significantly reduced when inertial data are employed. Cramer Rao lower bounds are computed to quantify the improvements in estimating motion parameters. A robust extended-Kalman-filter-based SfM algorithm using inertial data is then developed to fully exploit the inertial information. This algorithm has been tested by using synthetic and real image sequences, and the results show the efficacy of using inertial data for the SfM problem. PMID- 11760198 TI - Field enhancement in apertureless near-field scanning optical microscopy. AB - The near field of an apertureless near-field scanning optical microscopy probe is investigated with a multiple-multipole technique to obtain optical fields in the vicinity of a silicon probe tip and a glass substrate. The results demonstrate that electric field enhancements of >15 relative to the incident fields can be achieved near a silicon tip, implying intensity enhancements of several orders of magnitude. This enhancement arises both from the antenna effect of the elongated probe and from a proximity effect when the probe is near the substrate surface and its image dipoles play a role. PMID- 11760199 TI - Mission-driven evaluation of imaging system quality. AB - Image-quality criteria are usually intended to achieve the best possible image at a given sampling rate, which is ill-suited to applications where the detection of well-defined geometric and radiometric properties of scenes or objects are paramount. The quality criterion developed here for designing observation systems is based on properties of the objects to be viewed. It is thus an object-oriented imaging quality criterion rather than an image-oriented one. We also propose to go beyond optimization and calibrate a numerical scale that can be used to rate the quality of the service delivered by any observation system. PMID- 11760200 TI - Optical tomographic imaging of dynamic features of dense-scattering media. AB - Methods used in optical tomography have thus far proven to produce images of complex target media (e.g., tissue) having, at best, relatively modest spatial resolution. This presents a challenge in differentiating artifact from true features. Further complicating such efforts is the expectation that the optical properties of tissue for any individual are largely unknown and are likely to be quite variable due to the occurrence of natural vascular rhythms whose amplitudes are sensitive to a host of autonomic stimuli that are easily induced. We recognize, however, that rather than frustrating efforts to validate the accuracy of image features, the time-varying properties of the vasculature can be exploited to aid in such efforts, owing to the known structure-dependent frequency response of the vasculature and to the fact that hemoglobin is a principal contrast feature of the vasculature at near-infrared wavelengths. To accomplish this, it is necessary to generate a time series of image data. In this report we have tested the hypothesis that through analysis of time-series data, independent contrast features can be derived that serve to validate, at least qualitatively, the accuracy of imaging data, in effect establishing a self referencing scheme. A significant finding is the observation that analysis of such data can produce high-contrast images that reveal features that are mainly obscured in individual image frames or in time-averaged image data. Given the central role of hemoglobin in tissue function, this finding suggests that a wealth of new features associated with vascular dynamics can be identified from the analysis of time-series image data. PMID- 11760201 TI - Higher-order-statistics-based detection of vehicles in still images. AB - We present a statistical pattern recognition scheme for detecting vehicles in still images. The methodology involves pattern classification using higher-order statistics (HOS) in a clustering framework. The proposed method approximately models the unknown distribution of the image patterns of vehicles by learning HOS information about the vehicle class from sample images. Given a test image, statistical information about the background is learned "on the fly." An HOS based decision measure derived from a series expansion of the multivariate probability density function in terms of the Gaussian function and Hermite polynomials is used to classify test patterns as vehicles or otherwise. Experimental results on real images with cluttered background are given to demonstrate the performance of the proposed method. When tested on real aerial images, the method gives good results, even for complicated scenes. The detection rate is found to be quite good, while the false alarms are very few. The method can serve as an important step toward building an automated traffic monitoring system. PMID- 11760202 TI - Statistical algorithms for target detection in coherent active polarimetric images. AB - We address the problem of small-target detection with a polarimetric imager that provides orthogonal state contrast images. Such active systems allow one to measure the degree of polarization of the light backscattered by purely depolarizing isotropic materials. To be independent of the spatial nonuniformities of the illumination beam, small-target detection on the orthogonal state contrast image must be performed without using the image of backscattered intensity. We thus propose and develop a simple and efficient target detection algorithm based on a nonlinear pointwise transformation of the orthogonal state contrast image followed by a maximum-likelihood algorithm optimal for additive Gaussian perturbations. We demonstrate the efficiency of this suboptimal technique in comparison with the optimal one, which, however, assumes a priori knowledge about the scene that is not available in practice. We illustrate the performance of this approach on both simulated and real polarimetric images. PMID- 11760203 TI - Power coupled between partially coherent vector fields in different states of coherence. AB - A procedure is described for calculating the power coupled between collimated, partially coherent vector fields that are in different states of coherence. This topic is of considerable importance in designing submillimeter-wave optical systems for astronomy. It is shown that if the incoming field S has coherence matrix A, and the outgoing field D has coherence matrix B, then the power coupled is simply Ps = Tr(ATBT), where the elements of T project the basis functions of B onto those of A. A similar technique can be used to calculate the power coupled from the background of S to D. The scheme is illustrated by calculating the power coupled between two scalar, Gaussian Schell-model beams. The procedure can be incorporated into optical design software. PMID- 11760204 TI - Theoretical and experimental investigation of the extinction in a dense distribution of particles: nonlocal effects. AB - We report experimental measurements of the extinction in a suspension of dielectric spheres. We find that the model originally introduced by Keller is in good agreement with the data provided that nonlocal effects are properly taken into account. We also find that the simple criterion establishing the regime of independent scattering previously introduced is not consistent with our data. PMID- 11760205 TI - Monte Carlo simulations of electromagnetic wave scattering from a random rough surface with three-dimensional penetrable buried object: mine detection application using the steepest-descent fast multipole method. AB - We present a statistical study of the electric field scattered from a three dimensional penetrable object buried under a two-dimensional random rough surface. Monte Carlo simulations using the steepest-descent fast multipole method (SDFMM) are conducted to calculate the average and the standard deviation of the near-zone scattered fields. The SDFMM, originally developed at the University of Illinois at Urbana-Champaign, has been modified to calculate the unknown surface currents both on the rough ground and on the buried object that are due to excitation by a tapered Gaussian beam. The rough ground medium used is an experimentally measured typical dry Bosnian soil with 3.8% moisture, while the buried object represents a plastic land mine modeled as an oblate spheroid with dimensions and burial depth smaller than the free-space wavelength. Both vertical and horizontal polarizations for the incident waves are studied. The numerical results show that the TNT mine signature is almost 5% of the total field scattered from the ground. Moreover, relatively recognizable object signatures are observed even when the object is buried under the tail of the incident beam. Interestingly, even for the small surface roughness parameters considered, the standard deviation of the object signature is almost 30% of the signal itself, indicating significant clutter distortion that is due to the roughness of the ground. PMID- 11760206 TI - Semiclassical scattering of an electric dipole source inside a spherical particle. AB - Semiclassical scattering phenomena appearing in the far-zone scattered intensity of a point source of electromagnetic radiation inside a spherical particle are examined in the context of both ray theory and wave theory, and the evolution of the phenomena is studied as a function of source position. A number of semiclassical effects that do not occur for plane-wave scattering by the sphere appear prominently for scattering by an interior source. These include a series of scattering resonances and a new family of rainbows in regions of otherwise total internal reflection. Diffractive effects accompanying the semiclassical phenomena are also examined. PMID- 11760207 TI - Evaluation of the impact of finite-resolution effects on scintillation compensation using two deformable mirrors. AB - The impact of finite-resolution deformable mirrors and wave-front sensors is evaluated as it applies to fullwave conjugation using two deformable mirrors. The first deformable mirror is fixed conjugate to the pupil, while the second deformable mirror is at a finite range. The control algorithm to determine the mirror commands for the two deformable mirrors is based on a modification of the sequential generalized projection algorithm. The modification of the algorithm allows the incorporation of Gaussian spatial filters into the optimization process to limit the spatial-frequency content applied to the two deformable mirrors. Simulation results are presented for imaging and energy projection scenarios that establish that the optimal spatial filter waist to be applied is equal to the subaperture side length in strong turbulence. The effect of varying the subaperture side length is examined, and it is found that to effect a significant degree of scintillation compensation, the subapertures, and corresponding spacing between actuators, must be much smaller than the coherence length of the input field. PMID- 11760208 TI - Scattering of the transverse magnetic modes from an abruptly ended strongly asymmetrical slab waveguide by an accelerated integral equation technique. AB - We study the problem of the scattering of the first TM guided mode from an abruptly ended strongly asymmetrical slab waveguide by an improved iteration technique, which is based on the integral equation method with "accelerating" parameters. We demonstrate that the values of these parameters are related to the variational principle, and we save approximately 1-2 iterations compared with the case in which these parameters are not employed. The tangential electric-field distribution on the terminal plane, the reflection coefficient of the first TM guided mode, and the far-field radiation pattern are computed. Furthermore, a simple technique based on the Aitken extrapolation procedure is employed for faster computation of the higher-order solutions of the reflection coefficient. Numerical results are presented for several cases of abruptly ended waveguides, including systems with variational profile, while special attention is given to the far-field radiation pattern rotation and its explanation. PMID- 11760209 TI - Reflection and refraction of an arbitrary electromagnetic wave at a plane interface separating an isotropic and a biaxial medium. AB - Exact solutions are obtained for the reflected and transmitted fields resulting when an arbitrary electromagnetic field is incident on a plane interface separating an isotropic medium and a biaxially anisotropic medium in which one of the principal axes is along the interface normal. From our exact solutions for the reflected fields resulting when a plane TE or TM wave is incident on the plane interface, it can be inferred that the reflected field contains both a TE and a TM component. This gives a change in polarization that can be utilized to determine the properties of the biaxial medium. The time-harmonic solution for the reflected field is in the form of two quadruple integrals, one of which is a superposition of plane waves polarized perpendicular to the plane of incidence and the other a superposition of plane waves polarized parallel to the plane of incidence. The time-harmonic solution for the transmitted field is also in the form of two quadruple integrals. Each of these is a superposition of extraordinary plane waves with displacement vectors that are perpendicular to the direction of phase propagation. PMID- 11760210 TI - Polarization elements: a group-theoretical study. AB - The classification of polarization elements, the polarization affecting optical devices that have a Jones-matrix representation according to the type of eigenvectors they possess, is given a new visit through the group-theoretical connection of polarization elements. The diattenuators and retarders are recognized as the elements corresponding to boosts and rotations, respectively. The structure of homogeneous elements other than diattenuators and retarders are identified by giving the quaternion corresponding to these elements. The set of degenerate polarization elements is identified with the so-called null elements of the Lorentz group. Singular polarization elements are examined in their more illustrative Mueller-matrix representation, and, finally the eigenstructure of a special class of singular Mueller matrices is studied. PMID- 11760211 TI - Renal transport of antibiotics and nephrotoxicity: a review. AB - The renal excretion of a drug can essentially be divided schematically into three functional processes: glomerular filtration, tubular reabsorption and tubular secretion. When assessing nephrotoxicity, the tubular secretion system, which allows transport of the drug from the blood to the urine via the tubular cells, is particularly important. Historically, two distinct tubular secretion mechanisms have been described for drugs: one via organic cations and the other via organic anions. More recently, a third tubular secretion mechanism has been identified, mediated by P-glycoprotein. In the present review, a number of examples will be given relating to antibiotic-induced kidney damage determined via the tubular reabsorption mechanism (aminoglycosides, amphotericin B) and via the tubular secretion mechanism (cephalosporins, vancomycin), respectively. Drug transport within the tubular cells is the first fundamental stage in the onset of the nephrotoxic process. Knowledge of these concepts is important for the prevention of iatrogenic kidney damage, particularly in patients with underlying disease receiving concomitant treatment with several potentially nephrotoxic molecules. PMID- 11760212 TI - Preclinical and clinical pharmacology of biotherapeutic agents: Saccharomyces boulardii. AB - Probiotic agents are living microorganisms that, upon ingestion, exert health benefits beyond inherent general nutrition. In this context, we must differentiate between biotherapeutics as approved drugs and dietary supplements and food products containing probiotic bacteria that are not considered drugs. At present the only biotherapeutic agent which is prescribable in some European countries, indicated to relieve specific diseases, is the yeast Saccharomyces boulardii. In this review we consider the various preclinical and clinical aspects of biotherapeutics as basic drugs and the biotherapeutic powers of their use in the treatment of some surgical enteropathies. PMID- 11760213 TI - Topical 5-aminolevulinic acid and photodynamic therapy in dermatology: a minireview. AB - Photodynamic therapy (PDT) is a treatment modality using a photosensitizer, light and oxygen to cause photochemically induced selective cell death. When exposed to light with the proper wavelength, the topically applied photosensitizer or photosensitizer precursor can activate a biomolecule through electron transfer to yield free radicals or produce singlet oxygen from energy transferred from the excited sensitizer to molecular oxygen. The tissue damage is the result of the activation of reactive singlet oxygen or free radical production. Photodynamic therapy with topical application of 5-aminolevulinic acid (ALA) is a new technique and although it remains largely experimental, it has potential application for treatment of malignant skin tumors, various precancerous and selected benign skin diseases. This technique yields not only a high percentage of good therapeutic results but also excellent cosmetic outcome. This paper reviews the recently published data on clinical ALA-based PDT in dermatology. PMID- 11760214 TI - Phenothiaziniums as putative photobactericidal agents for red blood cell concentrates. AB - The antibacterial activities of Methylene Blue and several of its congeners were measured against Yersinia enterocolitica, a gram-negative pathogen known to exhibit significant growth at 4 degrees C and thus constituting a threat to red blood cell concentrates which are stored at this temperature. None of the derivatives was highly active in dark conditions, as expected, but on illumination using a lamp emitting light in the waveband 615-645 nm, considerable bactericidal activity was noted using similar photosensitizer concentrations to those used elsewhere to inactivate blood-borne viruses. Two novel compounds in this area, the phenothiazinium New Methylene Blue N and the phenoxazinium Brilliant Cresyl Blue, exhibited bactericidal activity at lower concentrations than both of the established phenothiaziniums, Methylene Blue and Toluidine Blue O and the recently published blood photovirucidal agent 1,9-Dimethyl Methylene Blue. The photoactivity of these compounds was undiminished in the presence of red blood cells. PMID- 11760215 TI - Influence of in-vivo endotoxin liberation on anti-anaerobic antimicrobial efficacy. AB - The ability of cefoxitin, clindamycin, imipenem, meropenem, metronidazole and piperacillin-tazobactam to cause gram-negative anaerobic bacteria to release endotoxin and the influence of such liberated endotoxin on antibiotic efficacy were investigated in in-vivo experiments in animal models. Experimental infections in various animal models (mice, hamster and infant rats) with cultures of wild and reference strains of Bacteroides fragilis group and Fusobacterium spp. were carried out by injecting these animals with different inocula (10(6), 10(7) and 10(8) cfu/ml) of the bacterial suspension, Appropriate doses of the test antibiotics were then injected and the plasma lipopolysaccharide (endotoxin) release measured by the Limulus Amoebocyte Lysate (LAL) Assay. Evidence of worsening of the outcome of the infections post-therapy was assessed, including histopathological changes in the internal organs. Infection with generalized septicemia was established with F. nucleatum in the mice and hamster models while with the B. fragilis group, infections only led to intra-abdominal abscess formation. Plasma endotoxin release was higher in animals infected with F. nucleatum than B. fragilis and was unrelated to the bacterial inoculum. Imipenem, meropenem and cefoxitin, in that order, induced the highest levels of endotoxin activities in the animal model, particularly following F. nucleatum infection. Histological examination of the internal organs of various animals showed variation in the pattern of histopathological changes; grades 3-4 inflammatory changes in the liver were observed in the Fusobacterium-infected animals that were treated with the carbapenems and cefoxitin. Therapy with the other antibiotics did not exacerbate anaerobic sepsis. In this study, bacteremia did not lead to massive endotoxin release and antibiotic therapy appeared not to have negatively influenced the outcome of most of the gram-negative anaerobic infections, except for infections caused by Fusobacterium spp. However, it is conceivable that if the gastrointestinal tract is the source of the endotoxin in patients with systemic inflammatory response syndrome, then the obligate anaerobes like Bacteroides and Fusobacterium species, which are members of the gut flora, may play a major role in the unfavorable outcome of antibiotic therapy in some of these infections. PMID- 11760216 TI - In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase. AB - 5-Fluorouracil (5-FU) is a pyrimidine antimetabolite active against colorectal carcinoma and other malignancies of the digestive tract. Over-expression or mutation of thymidylate synthase (TS), the target enzyme of the 5-FU metabolite, 5-fluorodeoxyuridine monophosphate, is strictly correlated with cancer cell resistance to 5-FU. On this basis we investigated whether TS is a potential target for active specific immunotherapy of human colon carcinoma, which acquires resistance to 5-FU. Three TS-derived epitope peptides which fit defined amino acid consensus motifs for HLA-A2.1 binding were synthesized and investigated for their ability to induce human TS-specific cytotoxic T cell (CTL) responses in vitro. CTL lines specific for each peptide were established by stimulating peripheral blood mononuclear cells (PBMC) from an HLA-A2.1+ healthy donor with autologous dendritic cells loaded with TS peptide. Specific CTL lines showed HLA A2.1-restricted cytotoxicity in vitro to HLA-A2.1+ target cells pulsed with the specific TS peptide and to HLA-class I matching colon carcinoma target cells over expressing TS enzyme after exposure to 5-FU. Recognition by CTL lines suggests that these TS peptides may be potential candidates for use in a peptide-based vaccine against 5-FU resistant colon carcinoma. PMID- 11760217 TI - IL-2-driven natural killer cell generation: role of anti-H-2b monoclonal antibodies and stromal cells in controlling quantitative and repertoire changes. AB - To investigate the role of major histocompatibility complex class I and bone marrow stromal cells on in vitro differentiation of natural killer cells, a CD44(low/-) CD2- population was isolated from mouse bone marrow. This NK-1.1- CD3 LFA-3+ B220+ population, when stimulated with IL-2 and co-cultured with supportive syngeneic stromal cells, generated populations of NK-1.1+ Ly49A+ Ly49C/I+ CD3- mature natural killer cells. The effect of anti-H-2b monoclonal antibodies (mAbs) on this phenomenon was assayed. Pre-adhesion of anti-H-2b mAbs to the stromal cells did not exert any effect, whereas when the same mAbs were pre-adhered to progenitors, there was a inhibition of natural killer cell generation that was maximum when the mAbs were added directly to cultures. In addition, the anti-H-2b mAbs did not inhibit the IL-2-induced proliferation of mature natural killer cells. Allogeneic but not H-2b-deficient stromal cells decreased the expression of Ly-49C/I but not Ly49A, thus suggesting that stromal cell haplotypes qualitatively influence the expression of Ly49s repertoire. PMID- 11760218 TI - Time-kill evaluation of antimicrobial regimens against clinical isolates of penicillin-resistant Streptococcus pneumoniae. AB - The rate of penicillin-resistant Streptococcus pneumoniae isolates in Spain is high. At present, penicillin and ceftriaxone are two drugs chosen for treating serious infections. In this study the bactericidal activity of four antimicrobial regimens against ten clinical isolates of S. pneumoniae (five with an intermediate resistance to penicillin and five highly resistant ones), was determined by means of kill kinetics studies using either penicillin, or ceftriaxone, in combination with vancomycin, or fosfomycin. The concentrations of the antimicrobial regimens (MICs 4x, 1x and 1/4x) were within possible physiological levels. While the combinations of penicillin, or ceftriaxone, plus vancomycin showed a significant increase in bactericidal activity, the bacterial reductions obtained in combination with fosfomycin were greater, achieving synergistic effects. These results suggest that in vivo trials with a regimen composed of ceftriaxone and fosfomycin would be worthwhile. PMID- 11760219 TI - Streptococcus pneumoniae penicillin resistance in Turkey. AB - Resistance of Streptococcus pneumoniae (750) to penicillin, erythromycin, chloramphenicol and trimethoprim/sulfamethoxazole isolated in 4 Turkish hospitals between 1996 and 1999 was evaluated according to year of isolation, patients' age groups and specimen. Penicillin susceptibility was determined by E-test strips and the other antibiotics were tested by disk diffusion test following the NCCLS guidelines in each center. Overall high and intermediate resistance to penicillin was 3% and 29%, respectively. There was a significant difference (p<0.001) between the centers with regard to penicillin resistance. However, there was no significant increase in resistance by year. Penicillin resistance varied significantly among children and adults (36% versus 25%) and according to the specimen. Highest rate of penicillin resistance was observed in respiratory specimens (36%) followed by ear exudates (33.5%). In blood isolates, resistance to penicillin was 28.6%. Overall resistance to erythromycin was 8%, to chloramphenicol 5% and to trimethoprim-sulfamethoxazole 47%. Although overall penicillin resistance in these Turkish S. pneumoniae isolates is high, resistance rates vary in each center and have not increased from 1996 to 1999. PMID- 11760220 TI - Clonal spread of imipenem-resistant Pseudomonas aeruginosa in the intensive care unit of a Turkish hospital. AB - Pseudomonas aeruginosa may cause life-threatening infections, especially in nosocomial settings. Although carbapenems are considered as one of the most effective alternatives in antipseudomonal therapy, resistance to the carbapenem group of antibacterials is a growing problem. In the first 6 months of 1997, P. aeruginosa isolates that were resistant to almost all antipseudomonal agents including imipenem were recovered from various specimens from intensive, care unit (ICU) patients. Isolates with the same antibiogram profile caused a small outbreak in May 1997. A retrospective case-control study revealed that the major risk factors for infection/colonization with multiresistant P. aeruginosa were prolonged stay in the ICU (p<0.001), previous and lengthy imipenem usage (p<0.001 and p<0.0001, respectively), and mechanical ventilation (p<0.001). Analytical isoelectric focusing of the sonicates prepared from the isolates showed that each isolate produced 1-5 beta-lactamases, enzymes with isoelectric points (pIs) of 5.1, 6.4, 8.5-8.7 being the most prevalent. DNA macrorestriction patterns of imipenem-resistant isolates were distinct from those of the imipenem-sensitive isolates recovered from ICU patients during the same interval and from the environmental isolates (controls). Thus, our results indicate that colonized patients appear to be the major source for cross-contamination of other patients and if imipenem is selected for empirical therapy, emergence of resistant strains should be anticipated and appropriate precautions taken. PMID- 11760221 TI - Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates. AB - The in vitro susceptibilities of 183 clinical yeast isolates to sertaconazole (STZ) were compared to their susceptibilities to clotrimazole (CTZ), econazole (ECZ), ketoconazole (KTZ), miconazole (MNZ), fluconazole (FLZ), itraconazole (ITZ), tioconazole (TCZ), amphotericin B (AMB) and flucytosine (5FC) by using a commercial agar diffusion method. Strains were isolated from vaginal and other superficial clinical samples (18 species of Candida and five strains belonging to other yeast genera). Only one strain (0.5%) was resistant to STZ out of 87.4% of susceptible strains (n=160). The percentage of susceptible strains was higher than those obtained with the other agents evaluated and the percentage of resistant strains was lower than for most of the other antifungals. The pattern of susceptibility of C. albicans to STZ, TCZ, ITZ and CLZ was similar and superior to the pattern of susceptibility of this species to MNZ, ECZ, FLZ, 5FC and KTZ. C. dubliniensis was more susceptible to STZ, MNZ, MNZ, FLZ, ITZ, CLZ than to TCZ, ECZ, 5FC, AMB or KTZ. Ten susceptible strains to STZ were resistant to FLZ and one strain was resistant to ITZ. The overall antifungal activity of STZ in vitro against a wide range of clinically important yeasts from vaginal and cutaneous samples indicates the therapeutic potential of this agent for the treatment of infections caused by these fungi. However, the activity of STZ and the clinical value of in vitro data need to be verified in human clinical trials. PMID- 11760222 TI - Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice. AB - The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients. Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin. Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study. Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v. dosing (4.19 vs. 4.87 L/h/kg). Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs. rifabutin pretreated: 1.18 h). The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs. 0.91 microg/mL) and a longer time to Cmax (Tmax: 0.17 vs. 0.33 h). These changes might be in part attributable to the increase in oral clearance (CL/F) by 18%. With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o. dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v. dosing. Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v. and p.o. dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38%. The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic. The therapeutic implications of this interaction, if any, remain to be defined. PMID- 11760223 TI - Nelfinavir suspension obtained from nelfinavir tablets has equivalent pharmacokinetic profile. AB - The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems. PMID- 11760224 TI - Role of gancyclovir and HAART administration in the treatment of a rare complication of HIV disease: cytomegalovirus-associated Guillain-Barre syndrome. AB - Peripheral nerve disorders are very common in patients with HIV infection, including inflammatory demyelinating polyneuropathies, such as Guillain-Barre syndrome. Causes of these neuropathies are probably multiple, and often dictated by the stage of the underlying HIV disease. Acute demyelinating polyneuropathy is usually preceded by infections, generally sustained by cytomegalovirus or Campylobacter jejuni, and a co-infection with HIV may represent the initial etiopathogenetic event leading to the neurological disorder. An extraordinary case report of a cytomegalovirus-associated Guillain-Barre syndrome occurred in one of our patients with advanced HIV infection, who was cured by gancyclovir and HAART administration, and gives us the opportunity to briefly discuss the intriguing pathogenetic and clinical correlations among HIV disease, cytomegalovirus infection, this neurological syndrome, and its specific treatment. PMID- 11760225 TI - Palliative care and genetics. PMID- 11760226 TI - Evaluating palliative care: facilitating reflexive dialogues about an ambiguous concept. AB - Palliation is a relatively new concept that is used in connection with the integral care provided to those who are unable to recover from their illness. The specific meaning of the concept has not been clearly defined. This article explores the possibilities offered by a responsive approach to evaluation that can facilitate a reflexive dialogue on this ambiguous concept. In doing so it draws on a case study of a palliative care project in a Dutch health care authority. The article begins with an overview of the characteristics of a responsive approach to evaluation and addresses interpretative, representational and practical dilemmas. It goes on to present a series of dialogues between health professionals, informal caregivers, patients and evaluators. These dialogues take the form of juxtaposed stories, transcribed conversations and interpretations. Finally, the learning experiences are summarised and the appropriateness of the responsive approach to evaluate palliative care is discussed. PMID- 11760228 TI - The care perspective and autonomy. AB - In this article I wish to show how care ethics puts forward a fundamental critique on the ideal of independency in human life without thereby discounting autonomy as a moral value altogether. In care ethics, a relational account of autonomy is developed instead. Because care ethics is sometimes criticized in the literature as hopelessly vague and ambiguous, I shall begin by elaborating on how care ethics and its place in ethical theory can be understood. I shall stipulate a definition of care ethics as a moral perspective or orientation from which ethical theorizing can take place. This will mean that care ethics is more a stance from which we can theorize ethically, than ready-made theory in itself. In conceiving care ethics in this way, it becomes possible to make clear that, for instance, a moral concept of autonomy is not abandoned, but instead is given a particular place and interpretation. In the final part of this article I will show how 'relational autonomy' can be applied fruitfully in the practice of psychiatric care. PMID- 11760227 TI - The undertreatment of pain: scientific, clinical, cultural, and philosophical factors. AB - This essay provides an explanation and interpretation of the undertreatment of pain by discussing some of the scientific, clinical, cultural, and philosophical aspects of this problem. One reason why pain continues to be a problem for medicine is that pain does not conform to the scientific approach to health and disease, a philosophy adopted by most health care professionals. Pain does not fit this philosophical perspective because (1) pain is subjective, not objective; (2) the causal basis of pain is often poorly understood; (3) pain is often regarded as a "mere" symptom, not as a disease; (4) there often are no "magic bullets" for pain; (5) pain does not fit the expert knowledge model. In order for health care professionals to do a better job of treating pain, some changes need to occur in medical philosophy, education, and practice. PMID- 11760229 TI - Genetics and culture: the geneticization thesis. AB - The concept of 'geneticization' has been introduced in the scholarly literature to describe the various interlocking and imperceptible mechanisms of interaction between medicine, genetics, society and culture. It is argued that Western culture currently is deeply involved in a process of geneticization. This process implies a redefinition of individuals in terms of DNA codes, a new language to describe and interpret human life and behavior in a genomic vocabulary of codes, blueprints, traits, dispositions, genetic mapping, and a gentechnological approach to disease, health and the body. This article analyses the thesis of 'geneticization'. Explaining the implications of the thesis, and discussing the critical refutations, it is argued that 'geneticization' primarily is a heuristic tool that can help to re-focus the moral debate on the implications of new genetic knowledge towards interpersonal relations, the power of medicine, the cultural context and social constraints, rather than emphasizing issues as personal autonomy and individual rights. PMID- 11760230 TI - Ethical boundary work: geneticization, philosophy and the social sciences. AB - This paper is a response to Henk ten Have's "Genetics and Culture: The Geneticization thesis". In it, I refute Ten Have's suggestion that geneticization is not the sort of process that can be measured and commented on in terms of empirical evidence, even if he is correct in suggesting that it should be seen as part of 'philosophical discourse'. At the end, I relate this discussion to broader debates within bioethics between the social science and philosophy, and suggest the need for philosophical approaches to take the social sciences seriously. PMID- 11760231 TI - The naturalness of the artificial and our concepts of health, disease and medicine. AB - This article isolates ten prepositions, which constitute the undercurrent paradigm of contemporary discourse of health disease and medicine. Discussion of the interrelationship between those prepositions leads to a systematic refutation of this paradigm. An alternative set is being forwarded. The key notions of the existing paradigm are that health is the natural condition of humankind and that disease is a deviance from that nature. Natural things are harmonious and healthy while human made artifacts are coercive interference with natural balance. It is suggested that the current paradigm is influenced by the world of finances and by instrumental reason. The alternative model suggests that human nature cannot be delineated. Humans fashion their own selves and nature by artificial means, medicine among them. The article discusses the implications of the paradigm adapted in various scholarly and popular debates such as the use of sex hormones for contraception, the care of the elderly, holistic medicine and distributive justice in health care. Medicine is not an isolated or a privileged realm. There is no unique entitlement to healthcare. It is always part of a broader agenda of social values and institutions. A open view of human societies, values and practices as they are situated within concrete material conditions is the platform required for an integrative and creative discourse of health care. PMID- 11760232 TI - The finitude of nature: rethinking the ethics of biotechnology. AB - In order to open new possibilities for bioethics, I argue that we need to rethink our concept of nature. The established cognitive framework determines in advance how new technologies will become visible. Indeed, in this dualistic approach of metaphysics, nature is posited as limitless, as material endowed with force which causes us to lose the sense of nature as arising out of itself, of having limits, an end. In contrast, drawing upon the example of the gender assignment and construction of intersexed infants, I want to suggest for bioethics an understanding of nature that arises not from our scientific explorations, but rather from attending to our situated perceptual encounters with the world which underlie such experimentation; these encounters are too easily overlooked, and yet they are crucial for opening up new ways of thinking. PMID- 11760233 TI - On the value-ladenness of technology in medicine. AB - The objective of this article is to analyse the value-ladenness of technology in the context of medicine. To address this issue several characteristics of technology are investigated: i). its interventive capacity, ii). its expansiveness and iii). its influence on the concept of disease, iv). its generalising character, v). its independence of the subjective experience of the patient. By this analysis I hope to unveil the double face of technology: Technology has a Janus-face in modern medicine, and the opposite of its factual face is evaluative. PMID- 11760234 TI - Is the self of the infant preserved in the adult? AB - What does a confrontation between philosophy and psychoanalysis look like? My task is a philosophical investigation of a psychoanalytic concept. Thus, I offer a conceptual analysis of a concept that is used both clinically and as a part of a metapsychology. The concept that I investigate in this article is regression. I work with the following two problems: What does a conceptual analysis of the phenomenon called "regression" look like? Regression can be regarded as an instrument that can give us knowledge about ourselves. What does this mean? I compare two ways of analyzing regression, an atomistic as well as an holistic approach. This comparison is made by way of a discussion of the conceptual analysis of the infant. Can we construct the inner life of the infant? How should we conceptualize the primitive? Using concepts like 'conceptual holism' and 'holism of attributes', I draw parallell conclusions about the construction of the infant's inner life and the analysis of the concept of regression. PMID- 11760237 TI - Medical education: investment or cost? PMID- 11760238 TI - Medical student debt and evidence-based politics. PMID- 11760239 TI - Medical student debt at the Christchurch School of Medicine. The New Zealand Wellbeing, Intentions, Debt and Experiences (WIDE) survey of medical students pilot study. Results part I. AB - AIMS: To determine the level and sources of medical student debt at the Christchurch School of Medicine. METHODS: A questionnaire, The New Zealand Wellbeing, Intentions, Debt, and Experiences (WIDE) Survey of Medical Students, was developed and administered to all 204 medical students at the Christchurch School of Medicine and Health Sciences. Included were questions on student demographics, sources and levels of debt, parental financial support, and student perceptions of their debt. RESULTS: The response rate was 88%. International students, whose debt was with an overseas government, and students with mortgages were excluded from the data analysis. The combined total debt for the remaining 165 students was $7775000 with $6290000 (81%) owed to the Government Students Loans scheme. One quarter of 6th year medical students had a debt over $83250, 50% had a debt over $70000, and 75% had a debt over $50000. Student allowances were inaccessible to 64% of 4th and 5th year students and part-time employment during term-time was common. Lack of funds was reported to impair full participation in the medical course. CONCLUSION: The majority of medical students at the Christchurch School of Medicine accumulate high levels of debt, mainly dtrough the Government Student Loans scheme, during their medical training. PMID- 11760240 TI - Medical student career intentions at the Christchurch School of Medicine. The New Zealand Wellbeing, Intentions, Debt and Experiences (WIDE) survey of medical students pilot study. Results part II. AB - AIMS: To record career preferences for medical students at the Christchurch School of Medicine and Health Sciences and investigate factors, including student debt, that might influence career decisions. METHODS: A questionnaire, The New Zealand Wellbeing, Intentions, Debt, and Experiences (WIDE) Survey of Medical Students, was developed and administered to all 204 medical students at the Christchurch School of Medicine and Health Sciences. The survey included questions relating to preferred career intentions and factors influencing career decisions, including the decision to leave New Zealand to practise medicine. RESULTS: The response rate was 88%. 80% intend to practise medicine in New Zealand immediately after graduation, however 82% indicated that they would leave within two years of graduation. Financial opportunities overseas and level of debt were the strongest motivating factors to leave. Repayments towards student loans and increased salaries were factors that might retain people in New Zealand. Medical and surgical specialities were the most popular career choices. Personal interest was the strongest motivator for career choice. Practising in a rural community was not popular. CONCLUSION: Debt is one of a number of important factors influencing medical student career decisions including the decision to leave New Zealand. Initiatives addressing debt may be useful in retaining medical graduates in this country. PMID- 11760241 TI - Debt on graduation, expected place of practice, and career aspirations of Auckland Medical School students. AB - AIMS: To determine the debt level that current Auckland medical students expect to graduate with, and evaluate this debt in the context of their career aspirations and intended place of practice. METHODS: Simple check-box and fill-in the-blank surveys were distributed to Auckland University medical students in Years 1 through to 5 during their second week of scheduled lectures in March 2000. Students were asked to provide demographic details, then complete sections on debt and career aspirations. RESULTS: 70% of Auckland medical students participated. Average expected debt was between $60000 to $70000. Predicted size of graduation debt was significantly related with plans to practice medicine overseas, and this trend was especially strong among females. In addition, Maori and Polynesian students bear a disproportionate level of the student debt burden compared to Pakeha and Asian groups. 77% of students indicated a preference for working in private or hospital specialty work. CONCLUSIONS: Student debt will have major effects on the composition of the New Zealand medical workforce over coming years. More attention must be paid to the national picture of medical student indebtedness if adequate workforce planning is to be possible. PMID- 11760242 TI - Smoke gets in your eyes: smoking and visual impairment in New Zealand. AB - AIM: To estimate the burden of visual impairment attributable to smoking in New Zealand. METHODS: Review of Medline-indexed literature on the relationship between smoking and eye disease and use of relevant New Zealand morbidity and smoking prevalence data. RESULTS: The international literature indicates there is strong evidence that smoking is a major cause of eye disease and blindness- particularly for cataracts and age-related macular degeneration (AMD). Using the most relevant international risk estimates, we estimated that 1335 people who are registered blind in New Zealand have AMD attributable to current and past smoking (26.8% of all AMD cases in the 55 years plus age-group). It was also estimated that 31 of the registered cases of visual impairment due to cataract and 396 hospitalisations for cataract surgery per year, are attributable to smoking. While subject to various methodological limitations, these estimates are probably under-estimates of the true burden of eye disease attributable to smoking. CONCLUSIONS: Smoking is a major cause of untreatable visual impairment and also a significant reason for cataract surgery in New Zealand. There is a need for more intensive tobacco control activities in New Zealand. PMID- 11760243 TI - The prevalence of faecal incontinence and constipation in a general New Zealand population; a postal survey. AB - AIMS: To determine the prevalence of constipation and faecal incontinence in the community. METHODS: A 20-question multi-field postal questionnaire was sent to 1500 adults (over 18 years) randomly selected from the electoral roll in the Canterbury region. Questions detailed frequency of bowel function, time spent at the toilet, incidence and severity of faecal incontinence, constipation, and the effect of disordered bowel function. RESULTS: Of 1500 questionnaires, 717 (48%) were returned (male: female 388:329). The median age was 46 years (range 18-70). 24 (4%) had self-reported gastrointestinal disease. There was a median frequency of seven bowel motions per week (BM/wk) (range 1 to 70) with 89% having between two motions a day and one every two days. Faecal incontinence affected lifestyle in 58 (8.1%). Incontinence of solid stool at least once a month occurred in 70 (9.8%), of liquid stool in 91 (12.7%), of gas in 459 (64%), while 12 (2%) regularly wore a pad. Those with self-reported gastrointestinal disease had a significantly higher (p<0.05) bowel motion frequency (17 vs 7 BM/wk) and median faecal incontinence score (2.5 vs 0). Laxatives were used by 4.9% of the population, while 26.2% increased fibre to avoid constipation. CONCLUSIONS: The normal frequency of bowel motions (+/- 2SD) was 2-17 per week. Faecal incontinence affecting life style affected 8.1%, while constipation requiring regular laxative use affected 4.9% of people. There is acceptance in the community that a moderate degree of bowel dysfunction is normal. Stool frequency and faecal incontinence scores can be used to predict those most likely to have organic gastrointestinal disease. PMID- 11760244 TI - Stem cells and neurodegenerative diseases. PMID- 11760245 TI - It won't happen again. PMID- 11760246 TI - Prostate cancer junked. PMID- 11760247 TI - Mentoring: a vital component for nurse faculty recruitment and retention. PMID- 11760248 TI - Millennium milestones: looking back, moving forward in your research career. AB - The author discusses the mission of the National Institute on Aging (NIA), Office of Special Populations, the trends in appropriations, use of census data and the need to disentangle the social and political meaning of race from the presumed biological meaning, the potential effect of slavery on the health of African Americans, Federal racial and ethnic minority initiatives, definitions of race, culture, ethnicity, class and racism; formal recommendations from the NIA review of minority aging research; and NIA training and career development opportunities for minorities. Lastly, the author discusses minority aging research, health disparities and strategies for recruiting minorities into aging research. PMID- 11760249 TI - Developing and implementing a model for online education for nurses. AB - This paper discusses the development and implementation of an online curriculum for Registered Nursing students in a rural area of Alabama, Mississippi and Louisiana using the eCollege system. PMID- 11760250 TI - Mentor/mentee relationship with the focus on meeting promotion/tenure guidelines. AB - Mentoring, an important concept in career development, is applied primarily in the literature to undergraduate students whereby faculty mentor students. This article discusses the development of a mentoring relationship in a complex university environment, factors that inhibit the development of a mentoring relationship, how to overcome these inhibitors and how attitudes can influence the mentoring relationship. Lastly, the development of a personal mentoring relationship is shared. PMID- 11760251 TI - Testing a life-style risk model in an Afro-American population. AB - This article discusses the results of a research study investigating the possible relationship between life-style risk factors, e.g., weight, dietary patterns, stress, activity and smoking in the development of diseases. The author concludes that there is a need for individuals to improve weight, dietary patterns, reduce stress and increase recreational activity to reduce life-style risk. PMID- 11760253 TI - Ethical principles and occupational health. PMID- 11760252 TI - Health promoting behaviors among rural southern early adolescents. AB - A central element in attaining the goals and objectives of Healthy People 2010 is promoting healthy behavior lifestyles. Health promotion continues to be sanctioned as the long term most cost effective approach to a reduction in preventable health problems. Adolescents are presently an age group in jeopardy of making the transition into adulthood with healthy lifestyles. This paper describes the use of the Health Promoting Lifestyle Profile (HPLP) (Walker, Sechrist, and Pender, 1987) as a measure of health promoting behaviors in a group of rural southern early adolescents (1036 seventh and eight graders; 81% were African American). The findings suggest that rural southern adolescents perceive themselves to be enganging in health promoting lifestyle behaviors. However, some HPLP subscales seemed to be especially difficult for adolescents. PMID- 11760254 TI - Confidentiality and disclosure of medical records under the Occupational Safety and Health Act. PMID- 11760255 TI - Workplace violence. PMID- 11760256 TI - Bereavement support. The occupational health nurse's role when death comes to work. AB - 1. Providing bereavement support for grieving employees can positively impact their adjustment and productivity. 2. Good bereavement care follows the nursing process approach: assessment, analysis, planning (goal setting), intervention/implementation, and evaluation. It acknowledges the five dimension of optimal health, and incorporates them into the nursing process. 3. The occupational health nurse, as clinician and advisor, can provide care to the bereaved individual and guidance to the manager and coworkers about the grief process and how to interact with the grieving employee. 4. Grief work is necessary for healing. The occupational health nurse can play a valuable role in facilitating the work by offering clinical support, a "safe" place for the grieving employee to talk about the death, referrals to the Employee Assistance Program or other professional support, and education about the process. PMID- 11760257 TI - Ecological model of occupational stress. Application to urban firefighters. AB - 1. Multiple individual and organizational barriers make it difficult for occupational health nurses and other providers to understand and handle stress in the workplace. 2. Recent research suggests adverse health effects resulting from occupational stress are more related to the context or conditions of work than workers' characteristics. 3. The ecological approach described in this article provides a means to examine the context in which stress occurs through an analysis of four levels of influence. The levels of influence include the microsystem, the organizational system, the peri-organizational system, and the extra-organizational system. 4. Through a careful analysis using this approach, an identification of the entire spectrum of factors contributing to the occurrence of workplace stressors can be identified, and more effective interventions addressing existing and potential problems related to occupational stress can be developed. PMID- 11760258 TI - Child care work. Organizational culture and health and safety. AB - A nonrandom sample of child care workers was surveyed to assess whether child care work represented an "at risk" health and safety culture and to measure the organizational dimensions contributing to the health and safety culture. The child care workers in Houston, Texas, were surveyed by mail, using an instrument developed by the research team. The sample population represented 34 child care centers (n = 240 respondents). The analysis yielded five factors related to determinants of health and safety culture. The participants had a favorable perception of the five health and safety determinants. The participants also reported high levels of injury and illness in their environments, suggesting a less than favorable situation. A culture, work, and health model was useful in examining the relationship between health and safety and organizational culture. PMID- 11760259 TI - Critical incident stress management. AB - Recent studies have indicated implementation of the CISM Program has impacted and reduced the cost of workers' compensation claims for stress related conditions and the number of lost work days (Ott, 1997; Western Management Consultants, 1996). Occupational health professionals need to be ready to develop and implement a comprehensive critical incident stress management process in anticipation of a major event. The ability to organize, lead, or administer critical incident stress debriefings for affected employees is a key role for the occupational health professional. Familiarity with these concepts and the ability to identify a critical incident enhances value to the business by mitigating the stress and impact to the workplace. Critical Incident Stress Management Systems have the potential for decreasing stress and restoring employees to normal life function--a win/win situation for both the employees and the organization. PMID- 11760260 TI - Body piercing: issues for A&E nurses. AB - There has been a significant increase in the incidence of body piercing in the Western world over the last decade. Although some A&E nurses have piercings of one type or another themselves, many have no experience of it. When confronted with a patient who has a problem associated with a piercing, there can be difficulties. However, even more anxiety seems to arise in emergency situations, when speed is crucial and health care professionals are unsure about how or when to remove jewelery. This piece reviews literature and takes advice from a professional piercer, regarding issues facing A&E nurses and how they can best be approached. Handling trauma, infection and embedded jewelery is described. Specific detail about piercing of the ear, nose, tongue, nipple, navel and genitals is included. Finally the role of the A&E nurse is identified in: when and how to remove jewelery, aspects of health education and raising awareness among staff. PMID- 11760261 TI - References and control of bullying. PMID- 11760262 TI - Factors affecting nurses' attitudes towards the screening and care of battered women in Dublin A&E departments: a literature review. AB - The concept of one human being inflicting unnecessary pain and suffering upon another, on a daily basis, is a disturbing and incredulous thought at the very least. This concept also known as domestic violence is all too real for the many victims presently suffering at the hands of their abusive partners. In Ireland, almost one in five women have experienced some form of domestic violence. This phenomenon can also be identified and further clarified as 'woman battering' Due to the confidential and accessible service offered to the client the Accident and Emergency department is a vital source of assistance to women who have been beaten by their partners. Battered women frequently present with injuries both visible and non-visible. More often than not however, many women are treated solely for their injuries and pass through the healthcare system unnoticed. Lydon (1996) estimates that of all presenting cases of domestic violence in the A&E department, only 5% are actually detected. Some literature estimates 3% detection rates (Thompson et al. 1998, Hadley, 1992). The following literature review explores the history behind the phenomenon of violence against women and its extent in Ireland. The literature affirming the important role of the nurse in A&E is reviewed and several themes are explored that affect nurses' attitudes in the screening and care of battered women. PMID- 11760263 TI - An Islamic understanding of health care: what can it teach us? AB - Supporting the case for employment and use of non-Christian health care chaplains in the National Health Service (NHS), the Runnymede Trust (1997) states: The inclusiveness or otherwise of a society is seen particularly clearly in the provision which it makes for its members when they fall ill, and perhaps especially when they spend extended time in hospital. At this point of stress and distress in the lives of individuals and their families, are people helped to "maintain their own culture, traditions, language and values"? The Patient's Charter of 1991 requires that health care providers should ensure "respect for privacy, dignity and religious and cultural beliefs".... One way of helping to ensure that such respect is shown is through the appointment of hospital Chaplains.' Although the Patient's Charter (Department of Health 1991) and the subsequent NHS Management Executive document HSG (92)2 (Department of Health 1992) required provision for the religious needs of all patients, in reality, apart from a few exceptions, it led to the appointment of more Church of England Chaplains (Beckford and Gilliat, 1996). Recognizing this problem, Reid and Clarke (1998) indicated NHS Executive willingness to redraw these documents 'provided it comes in the form of a common agreed approach to all faith communities, on the status of chaplaincy and spiritual care in the NHS'. PMID- 11760264 TI - Lynn Sbaih interviews Karen Castille, director, Emergency Services Programme, National Patients' Access Team, NHS Executive. PMID- 11760265 TI - Opportunity for audit: establishing and monitoring the use of protocols for nurse led treatments of minor injuries. AB - During the last three years an integrated initiative has evolved in the casualty units of nine community hospitals in the Grampian region of Scotland. This has involved the development of nurse-led treatments for minor injuries based on a large number of assessment/treatment protocols. This paper describes how this change was used as an opportunity to initiate audit within clinical practice. Methods of auditing the use of the new protocols are detailed and baseline results are reported and discussed. In this way it is hoped that nurses involved in similar developments can learn from the strengths and weaknesses of this initiative. PMID- 11760266 TI - Isabella Treece, NIWI grant recipient. Interview by Eileen Lukes. PMID- 11760267 TI - The Policy and Procedure manual--keeping it current. PMID- 11760268 TI - PMS in the workplace. An occupational health nurse's guide to premenstrual syndrome. AB - 1. Premenstrual syndrome (PMS) is defined as the cyclic recurrence of physical, psychological, or behavioral symptoms that appear after ovulation and resolve with the onset of menstruation. These symptoms can be severe enough to disrupt personal relationships, social activities, or job performance. 2. The exact cause of PMS is unknown. The best tool to diagnose PMS is a daily symptoms rating calendar. To have the diagnosis of PMS, the symptoms must be severe enough to disrupt normal daily activities. 3. The occupational health nurse can provide information about first line treatment modalities for PMS symptoms including dietary modifications, nutritional supplements, aerobic exercise, and stress management skills. 4. More research is needed about PMS in the workplace and the effect of treatments on outcomes such as job attendance and work performance. PMID- 11760269 TI - Exercise behavior among female occupational health nurses. Influence of self efficacy, perceived health control, and age. AB - Physical fitness of the American worker is a core element of personal good health and a key factor in corporate cost containment. The Centers for Disease Control and Prevention specifically notes that health professionals should be physically active not only to benefit their own health but also to make more credible their endorsement of an active lifestyle. Guided by Pender's Health Promotion Model, this study gives a profile of the current status of exercise behaviors, physical self efficacy, and perceived health control among a sample of occupational health nurses. Surveys were mailed to a random sample of 300 female members from a midwestern state association of the American Association of Occupational Health Nurses. The mean exercise score was 30.7 MET hours per week, with walking the activity most often selected. Physical self efficacy was a significant positive predictor of exercise practice, while age exerted a significant inverse effect on exercise. The study findings may be used to stimulate discussion among occupational health nurses about how their own physical self efficacy and perceived health control may influence their exercise behaviors, and how in turn these beliefs and exercise practices may influence their decisions about promoting exercise programs at their workplaces. PMID- 11760270 TI - Information seeking behavior of occupational health nurses. How nurses keep current with health information. AB - A questionnaire designed to study the information seeking behavior of professional nurses was mailed to 600 occupational health nurses who work and reside in New York State. A 28% response rate (165 usable replies) was obtained. Results indicated respondents most need to know about government regulations relating to health care, new developments in their area of specialization, drug information, and the psychological aspects of disease. The respondents most frequently looked to peers and colleagues in their agency, personal files and books, and professional organizations as important sources of information. Whereas respondents were less apt to rely on the Internet, MEDLINE, or the hospital library as sources of information used for professional purposes, 38.8% did report they frequently used the Internet to seek health related information. Also, the majority of respondents (65%) indicated interest in continuing education, if it were available, in using the Internet to access health related information. The present study suggests professional nursing organizations have an opportunity to meet members' needs by expediting members' efforts to access and evaluate information using emerging information technologies. PMID- 11760271 TI - Automatic external defibrillator intervention in the workplace. A comprehensive approach to program development. AB - 1. The planning and implementation of an automatic external defibrillator (AED) intervention in the workplace necessitates a comprehensive approach to program development. 2. Initiation of an AED intervention program at the worksite, based on an informed decision, requires each company to conduct a detailed assessment of need. 3. Prior to initiating an AED intervention program, appropriate resources should be consulted to examine national, state, and local law provisions and legal factors governing AED use in each specific community. 4. Essential components of an AED intervention program include: the combined cardiopulmonary resuscitation and AED use training program; written policies, procedures, and medical directives; a plan for the purchase, maintenance, and location of the AED equipment and supplies; an integrated emergency response plan; and an ongoing quality improvement process. PMID- 11760272 TI - Why a code of ethics? PMID- 11760273 TI - Work force diversity. Implications for occupational health nursing. AB - 1. Increasing work force diversity is reflected in the Healthy People 2010 goal to eliminate health disparities. 2. At the organization level, a framework of cultural competence defines the developmental process toward cultural proficiency. 3. Strategies are suggested for organizations and nurses to engage in cultural competence. PMID- 11760274 TI - Limited English proficiency workers. Health and safety education. AB - 1. As the population of adults with limited English proficiency plays an increasingly important role in the United States workplaces, there has been a growing recognition that literacy and limited English skills affect health and safety training programs. 2. Several important principles can be used as the underlying framework to guide teaching workers with limited English proficiency: clear and vivid way of teaching; contextual curriculum based on work; using various teaching methods; and staff development. 3. Two feasible strategies were proposed to improve current situation in teaching health and safety to workers with limited English proficiency in one company: integrating safety and health education with ongoing in-house ESL instruction and developing a multilingual video program. 4. Successful development and implementation of proposed programs requires upper management support, workers' awareness and active participation, collaborative teamwork, a well structured action plan, testing of pilot program, and evaluation. PMID- 11760275 TI - Occupational health nursing with Navajo workers. Providing culturally competent care. AB - 1. Native Americans in the southwestern United States are considered a "vulnerable population." Native Americans have economic difficulties, poor health, and little access to health care. The Navajo nation is the largest Native American reservation in the United States. 2. Occupational health nurses who provide culturally competent care increase the likelihood for Navajo workers to obtain optimal benefits from workplace health services. 3. The nurse uses cultural assessment skills and critical thinking abilities to maximize therapeutic interactions and minimize barriers in communications with workers of other cultural backgrounds. 4. The nurse who is knowledgeable about the Navajo way can help achieve a balance between the traditional ways and Western ways of addressing serious health care issues facing the Navajo worker. This knowledge and cultural awareness also increases the effectiveness of health promotion and health education programs offered to workers, their families, and their communities. PMID- 11760276 TI - Cultural sensitivity and day care workers. Examination of a worksite based cardiovascular disease prevention project. AB - Reaching workers in small worksites presents economic and access barriers for occupational health nurses. Some barriers can be overcome through strategies based on cultural sensitivity. Day care centers employ young, low income, mostly minority women in settings with few workers onsite at any one center. These settings were used to develop a culturally sensitive approach tested through onsite cardiovascular screening, informal interviews, and discussion of behavior change for better health. The study examined both the impact of the Healthier People Health Risk Appraisal (HPHRA) as a culturally appropriate recruitment strategy to involve a group of child day care workers in a cardiovascular disease (CVD) screening and risk reduction program and the effect of that program on observable CVD measures. Faculty and students from an institution of higher education forged a trust relationship with day care providers at nine day care centers in a large metropolitan area. Cardiovascular health was the impetus for the project because minority populations in the southeastern United States have high heart attack and stroke mortality and morbidity rates. Participation rates in the project increased from 26% of the day care workers in the first year of the project to 73% when long term relationships were built on culturally appropriate strategies. The project's culturally sensitive educational intervention focused on individual risks and lifestyle. Statistical analysis of outcomes of the intervention and personal interviews demonstrated the improvement of cardiovascular status in the day care workers. This psychosocial approach can provide the foundation for culturally sensitive care in larger occupational and community settings. PMID- 11760277 TI - Self assessment for quality and assurance. An essential component of effective health care delivery at the worksite. AB - Programs designed to ensure high quality performance, whatever name they are given, have the same basic elements. They measure compliance with established standards, provide feedback, institute changes as necessary to improve outcomes, and measure again. The first steps include determining which programs need evaluation and identifying the standards. Measurement tools are then developed and the self assessment takes place. After the results are analyzed, the necessary program changes are made, and the cycle is repeated. Failure to determine levels of compliance with government regulations can leave a company vulnerable to sanctions if noncompliance is significant. Self identification of problems before they become apparent outside the department allows the occupational and environmental health nurse to make program and process improvements before the problems become crises. Self assessments are designed to monitor activities, determine program or procedure effectiveness, validate decision making, and investigate unsolicited observations and comments. Self regulation is the hallmark of a mature profession (Phaneuf, 1972), and as such, occupational and environmental health nurses have a professional responsibility to actively engage in formalized self regulation activities. PMID- 11760279 TI - Position statement. The occupational health nurse's role in preventing and reducing workplace violence. PMID- 11760278 TI - A 10 step path for conflict resolution. PMID- 11760280 TI - Over-the-counter medications. PMID- 11760281 TI - Will there be an increase in workers' compensation claims? PMID- 11760282 TI - Accessing the Internet. PMID- 11760283 TI - The impact of educational research centers on occupational health and safety alumni competence. A program evaluation. AB - 1. A 10 step method for program evaluation can be used to evaluate the success of a program in meeting its major goals and objectives. This evaluation examined the 20 year impact of the Midwest Center for Occupational Health and Safety, a NIOSH supported Educational Research Center, on its alumni. 2. The majority of alumni (89%) reported the primary focus of their work after graduation was the provision of occupational and environmental health and safety products and services- consistent with the legislative intent of Educational Research Centers (ERC). 3. Alumni reported the most highly valued ERC products and services included interdisciplinary interactions during and after graduate school, research training, and the presence of the ERC as a regional focal point for occupational health and safety graduate and continuing education. 4. The program evaluation design and survey instrument employed in this study are recommended for adaptation by other ERCs or educational programs faced with the challenge of providing evaluation data with minimal resources. PMID- 11760284 TI - Working with labor unions. What occupational health nurses need to know. AB - 1. The work of many occupational health nurses involves interaction with labor unions in a range of settings, yet little training is provided to understand unions and their role. 2. Understanding the structure and function of unions can help nurses work more effectively in collaboration with labor toward the common goal of reducing workplace injury and illness. 3. Nurses need to educate union members and leadership to better understand the full range of skills and responsibilities of occupational health nurses. PMID- 11760285 TI - Reducing barriers to reach more women for breast cancer services results of consumer focus groups. AB - In 1999, approximately 19,000 women in California were diagnosed with breast cancer and 4600 died. Early detection, education and treatment are critical services in combating the disease. In 1999, 42 low income women, 40 years and older participated in focus groups throughout California. Focus group results revealed valuable information regarding barriers to breast cancer early detection services. PMID- 11760286 TI - Prostate screening health beliefs and practices of African American men. AB - The purpose of this study was to investigate the health beliefs and practices of African American men regarding prostate cancer screening. A descriptive non experimental design was used with a self-administered questionnaire to identify participants' knowledge level, health beliefs and practices related to the screening and early detection of prostate cancer in African American men. Results indicate that most participants had a high level of prostate cancer knowledge, early detection and had prostate screening done on a regular basis. They believed prostate cancer was not preventable but if contracted treatment would be painful and impair sexual function. Other significant beliefs included: good health habits were important, most rated their health as good or excellent, and they rely on their faith to stay healthy. Findings of this study provide culturally appropriate information which may contribute to developing prostate cancer prevention programs in African American communities. PMID- 11760287 TI - The effects of community, coworker and organizational support to job satisfaction of nurses in Cameroon. AB - This study examined the effects of community, co-worker and organizational support with the job satisfaction of nurses in Cameroon in six major components of the job namely; work, pay, promotion, supervision, co-worker relationships and the job in general. Each variable was examined separately. A convenience sample of 158 staff nurses, participated in this study. The Job Descriptive Index (JDI) questionnaire and the Job In General (JIG) scales were used to measure job satisfaction. Focus group interviews and a content analysis of major themes were conducted. Inferential statistics were used to test the effects of community, co worker and organizational support and job satisfaction. Results showed significant, positive effects between perceived level of community support, coworker support and organizational support with components of job satisfaction sub-scales. These results are useful for nurse educators, and researches in the formulation and implementation of effective health policies for nurses and health care organizations. PMID- 11760288 TI - Reducing asthma morbidity and mortality. Cost containment strategies. AB - 1. Asthma is the third leading cause of preventable hospitalization in the United States and has accounted for more than 3 million lost workdays. 2. Understanding the stepwise approach and the medications used to control asthma can reduce exacerbations which can contribute to reduction in costly emergency department visits. 3. Education is the key to controlling asthma. Encouraging effective daily peak flow monitoring, taking medications as directed, avoiding asthmatic triggers, and correctly using prescribed inhalers helps curb the spiraling costs of lost workdays. PMID- 11760289 TI - Initiating an ergonomic analysis. A process for jobs with highly variable tasks. AB - Occupational health nurses play a vital role in addressing ergonomic problems in the workplace. Describing and documenting exposure to ergonomic risk factors is a relatively straightforward process in jobs in which the work is repetitive. In other types of work, the analysis becomes much more challenging because tasks may be repeated infrequently, or at irregular time intervals, or under different environmental and temporal conditions, thereby making it difficult to observe a "representative" sample of the work performed. This article describes a process used to identify highly variable job tasks for ergonomic analyses. The identification of tasks for ergonomic analysis was a two step process involving interviews and a survey of firefighters and paramedics from a consortium of 14 suburban fire departments. The interviews were used to generate a list of frequently performed, physically strenuous job tasks and to capture clear descriptions of those tasks and associated roles. The goals of the survey were to confirm the interview findings across the entire target population and to quantify the frequency and degree of strenuousness of each task. In turn, the quantitative results from the survey were used to prioritize job tasks for simulation. Although this process was used to study firefighters and paramedics, the approach is likely to be suitable for many other types of occupations in which the tasks are highly variable in content and irregular in frequency. PMID- 11760290 TI - Occupational hazards in female ballet dancers. Advocate for a forgotten population. AB - 1. Personal, economical, psychological, and physical factors increase a ballet dancer's stress, which can result in a higher risk for injuries. 2. Ballet dancers experience injuries to the foot, ankle, knee, hip, or back. The constant fear of injuries is universal among dancers because injuries can lead to permanent disability and the end of their ballet career. 3. Although early treatment of injuries is critical, there are multiple barriers to receiving treatment. Some of the barriers include misunderstanding from the health care community, cost of treatment, time constraints, fear of unemployment, and dancers' viewing injuries and pain as a way of life. 4. Occupational health nurses are in an excellent position to start programs in this unexplored area of occupational health nursing. Nurses must advocate for this population of workers and help dancers in their battle against injury, pain, disability, and psychological distress. PMID- 11760291 TI - High risk pregnancy in the workplace. Influencing positive outcomes. AB - Childbearing employees are well served by the occupational health nurse who promotes optimal preconceptual and pregnancy health practices, uses community resources, and maintains current knowledge about high risk pregnancy prevention and care. These broad goals of care can lead to decreased absenteeism, healthier and happier employees, and more positive outcomes of pregnancy. For employees with high risk pregnancies, the role of the occupational health nurse includes, but is not limited to, facilitating awareness with the employer, making suggestions for adjusting working conditions, making frequent assessments of the employee's needs, and communicating with prenatal health care providers. Occupational health nurses should never underestimate their role and potential influence on the mother, and on her significant other, for a positive outcome of her pregnancy. PMID- 11760292 TI - Burnout and the power of one. PMID- 11760293 TI - Exercise and dietary behaviors in African American elders: stages of change in efficacy expectancies. AB - The purpose of this pilot study was to measure and describe stages of change and efficacy expectancies of African American elders in regard to exercise and dietary behaviors. Elders who had hypertension (N = 37) were recruited from a senior center and a public housing building for the elderly. These elders were found to be in the action and maintenance stages of change. They believed that they were able to perform healthy exercise and dietary behaviors and that these behaviors were effective in relation to their hypertension. Implications of the finding are discussed in regard to exercise and dietary behaviors and health promotion programs for this high-risk population. PMID- 11760294 TI - The impact of a College of Nursing Retention Program on the graduation rates of nursing students. AB - This study was designed to measure the impact of a College of Nursing's (CON) Retention Program on students enrolled in a baccalaureate degree nursing program. Within the last ten years, undergraduate nurses increasingly have utilized the CON retention program. These students traditionally face a number of barriers to their academic endeavors. This study was designed to assess the effect of the CON program on the barriers to academic success of students who entered the CON in the Fall classes of 1991, 1992 and 1993. The sample size was 320 students. The control group consisted of 137 students who received no intervention and the experimental group was comprised of 183 students who attended intervention sessions with the Retention Coordinator in the CON. It was hypothesized that the most successful students during this period (1991-1993) were the most frequent attendees of the CON retention program intervention sessions. The alternative hypothesis was that those persons who did not attend the sessions, but were still highly persistent and successful, were enrollees who had entered with high entrance credentials as demonstrated by the transfer grade point averages (GPA). The results of this study indicated the need, use and value of this systematic approach to retention. PMID- 11760296 TI - Fostering Healthy Communities @ Hair Care Centers. AB - The author discusses the planning and development of a unique method of reaching African American clients by Chi Eta Phi Sorority, Inc. members in the state of South Carolina through use of beauty shops and barber shops, which is termed Hair Care Centers. Using bulletin boards which are placed in these establishments, the members of Chi Eta Phi Sorority, Inc. change the educational materials monthly based on the minority health awareness themes created by the Office of Minority Health in Washington, DC. The goal of Project F-HC is to take self-care, health promoting, disease prevention information to places where persons frequent, making it easily accessible. PMID- 11760295 TI - Social support and postpartum African American women. AB - The birth of the first child is a major transitional period for the new mother and her family. Social support that women receive seems to buffer the changes experienced during the postpartum period. However, very little is written about the social support of postpartum African American women. The purpose of this pilot study was to investigate the difference between social support expected prenatally, and that actually received postpartally in African American primiparous women. Data were collected utilizing a modified version of the Postpartum Social Support Questionnaire. Findings revealed no significant differences in the social support expected, and what was actually received postpartally. This sample was somewhat unique in that the women were educated with at least a high school education, with a mean age of 25, and possessed health insurance (access to health care). Future research utilizing the tool with larger samples should be conducted to further validate the reliability and validity of the tool. PMID- 11760297 TI - Perceptions of one African American community about its' health, health status and safety. AB - African Americans remain at the low end of the socio-economic stratum, have less health care access, and have the highest mortality from illnesses. This supports a need for African American nurses to enter African American communities to offer health education/literacy sessions. This project conducted a survey to determine the health status of African Americans living in a select section eight housing area and their perception of their health, health status and safety. Participants identified their health and health status as good. They had a high concern about safety in their neighborhood. Earlier reports from the county and state do not support the respondents' belief about their health or health status. These same reports do support the respondents concern for safety. PMID- 11760298 TI - Combining technology and skill to ensure effective meetings. PMID- 11760299 TI - Planning a hepatitis C postexposure management program for health care workers. Issues and challenges. AB - 1. Approximately 4 million individuals in the United States are infected with hepatitis C virus (HCV), many of whom are unaware of this infection. Thus, health care workers are faced with the potential for needlestick and blood exposure to another bloodborne pathogen in addition to hepatitis B and HIV. 2. The Centers for Disease Control and Prevention recommended that health care facilities follow guidelines from the U.S. Public Health Service for prevention and control of HCV infection. 3. Hospitals and other health care institutions must consider legal, ethical, and health issues and outcomes when formulating a comprehensive postexposure program for hepatitis C. 4. The occupational health professional can play an integral role in both postexposure management and prevention of HCV exposures in the health care setting. PMID- 11760300 TI - Health problems associated with international business travel. A critical review of the literature. AB - 1. Few studies examine the travel related health problems of international business travelers (IBTs). Research exists for other travelers, such as tourists, which begins to help clinicians understand the potential health problems faced by IBTs. 2. A review of the literature reveals 36% to 54% of travelers experience physical health problems such as traveler's diarrhea, insomnia, respiratory problems, and skin problems; 6% to 18% report accidents and injuries while abroad. 3. Psychosocial data are equally limited, but support the idea that IBTs may experience stress, anxiety, culture shock, and adjustment problems while overseas. 4. Multiple factors likely contribute to the physical and psychosocial health experiences of IBTs. The historical lack of data for this population of workers combined with the trend towards globalization confirm the need for further study from an occupational health perspective. PMID- 11760301 TI - Carpal tunnel syndrome. Testing the sensitivity and validity of four "localized discomfort" instruments. AB - A convenience sample of 52 participants was used to examine the construct validity and sensitivity of four "localized discomfort" instruments and the severity of clients with carpal tunnel syndrome, using the "known group" method. Three groups known to have severe, mild, or no carpal tunnel syndrome based on either nerve conduction studies or an inability to complete a physical challenge (exercise) were used. The participants rated the amount of localized discomfort for one hand, wrist, and arm on four different instruments. Following a physical challenge, strenuous enough to result in an increase in localized discomfort, the four instruments were readministered. The difference in the pre- and posttest scores was compared for both sensitivity and validity. The ease of administration of the four instruments was also assessed. All four instruments were found to demonstrate sensitivity. Two of the four instruments, the Unipolar Borg Scale and the first Visual Analog Scale, were found to be most valid and easiest to administer. Occupational health nurses could use these two valid and sensitive tools as early markers for future injury. The tools also could be used to measure the progress of an intervention or therapy following an injury and gauge readiness for return to work. PMID- 11760302 TI - The occupational health service. Staffing, facilities, and equipment. AB - An occupational health service can be an integral part of any company. It is incumbent on the industry to conduct a thorough assessment of the need for such a service and then support the service from a financial and resource perspective. Consequently, staffing and equipping an occupational health service adequately are dependent on the services to be delivered and the type of professional staff hired. All occupational health programs can be conducted in a cost effective manner when the goals and mission are in alignment with company goals, management supports appropriate funding, and space supports the delivery of quality health care. PMID- 11760303 TI - Transition management--an effective means to the desired outcome. PMID- 11760304 TI - Corneal foreign bodies--first aid, treatment, and outcomes. Skills review for an occupational health setting. AB - Eye injuries from foreign body incidents remain prevalent in the workplace setting. Often the professional nurse provides the first line of treatment. The informal class presented at the authors' facility offered a comprehensive, organized presentation of a common injury encountered in the practice of occupational health nursing. Strenghts of the presentation included handouts demonstrating eye eversion technique and a flip chart summarizing the content to be placed in each medical station as quick reference. One challenge involved presenting the information to all nurses. The site encompasses four locations and some nurses function as the only staff in the plant for a given shift. With the support of administration and some creative scheduling, 10 of 17 nurses attended one of three classes offered in one morning, and the remaining 7 were able to view the class on videotape. Videotaping the presentation also provided material for future orientation, as well as an opportunity for review. Overall analysis found this a worthwhile offering relevant to practice. A brief formal written evaluation indicated the objectives for the class were achieved and elicited subjects for future topics. Informal chart reviews to check for documentation of visual acuity testing and eversion of the upper lid for foreign body injuries is another outcome measure currently in progress. In addition, a performance improvement project could be accomplished easily by retrospective chart review of assessment and treatment documentation, and tracking of revisits and referrals. Knowledge of current standards in the assessment, first aid, and treatment of eye injuries is every occupational health nurse's responsibility. However, prevention of foreign body injuries is far superior to any treatment modality available. As highly visible leaders within the occupational setting, nurses can be advocates and role models for safe work practices. Occupational health nurses may promote safe eye practices by actively seeking collaboration with safety departments to continuously monitor and improve eye injury and outcome statistics and use of protective eye-wear. By consistently wearing proper safety eyewear, such as approved goggles or prescription safety glasses with side sheilds, during each and every venture into the work area, occupational health nurses provide a strong role model and have the opportunity to educate employees and encourage safe work practices. It is important to encourage shared responsibility and awareness between workers and management for prevention of foreign body incidents and prompt, accurate treatment when necessary to promote optimal outcome. PMID- 11760305 TI - Occupational safety and health training on the Internet. Developing quality instruction. AB - 1. Training via the Internet (e-training) for adults must be based on the following principles: (1) learning is an active process wherein the learner constructs knowledge rather than acquires it and (2) instruction is a process of supporting this construction rather than communicating knowledge. E-training can successfully accommodate such features using available technologies. 2. Because e training is self directed, it is uniquely adaptable to learners with different learning styles, interests, and cultural beliefs. E-training also affords flexible pacing, which is ideal for instruction aimed at both new and experienced workers. 3. As the predicted global economy becomes reality, qualified OSH personnel will be needed on a global scale. To meet new and evolving needs worldwide, professionals must have access to information and training regardless of location. E-training is the most promising approach to meeting this demand. 4. Currently, occupational safety and health e-training does not fulfill its potential. Most training programs do not encourage higher level cognition, critical thinking, or transfer of knowledge. Therefore, training effectiveness research is needed to improve the state of e-training. PMID- 11760306 TI - Occupational health surveillance strategies for an ethnically diverse Asian employee population. AB - 1. Implementation of a medical/health surveillance program can prevent the damaging effects of lead toxicity. Lead toxicity may be a result of acute or chronic exposure and can affect the hematopoietic, nervous, renal, and reproductive systems. 2. Minority groups tend to be overrepresented in lead industries. Further, an increase in high lead levels can be compounded by cultural influences. Education must be geared toward the specific employee populations. 3. Successful programs require assistance from all team members- occupational health nurse, safety engineer, industrial hygienist, and environmental engineer. Occupational health nurses play an important role in implementation of medical/health surveillance programs by scheduling regular blood testing, monitoring results, and educating employees. PMID- 11760307 TI - Tobacco abuse and its treatment. Turning old and new issues into opportunities for the occupational health nurse. AB - 1. Tobacco use is linked to excessive rates of cardiovascular disease, lung disease, and many fatal neoplasms. In the United States it is the number one cause of illness and premature death. Cigarettes and other combusted forms of tobacco generate environmental tobacco smoke, a major contributor to asthma attacks, heart attacks, and lung cancer among nonsmokers. 2. Cigarettes are the most prevalent and abused form of tobacco, but other forms, such as cigars and smokeless tobacco, also contain nicotine and may cause dependency in high risk groups that consume these products. 3. The addictiveness of tobacco products, especially cigarettes, is particularly detrimental to vulnerable groups such as youth, women, blue collar workers, and other high risk and economically disadvantaged populations. 4. Effective treatment programs (e.g., individual and group counseling, close monitoring, drug treatment) are available to treat nicotine dependency, but many health care providers have been reluctant to educate their patients and clients about these programs. 5. Workplace tobacco use treatment programs, along with policies to restrict tobacco use, have special merit for employers concerned with worker health and safety, productivity, and profitability. Even the more successful tobacco treatment programs perform better when combined with additional efforts to reduce worker health risks and promote well being. PMID- 11760308 TI - Elder care issues in the workplace. PMID- 11760309 TI - Community health, media, and policy in sub-Saharan Africa: a primary prevention approach to the AIDS crisis. AB - Availability, access and utilization of essential health services present challenges to community health services in Sub-Saharan Africa. HIV/AIDS infection has added yet another dimension to a continent already experiencing economic crises. A primary prevention approach is emphasized as a means of addressing sexual behaviors that decrease risk of transmission. Educating the sexually active to use condom and also HIV/AIDS testing and counseling can be effective in curbing transmission of the virus. Community forums such as the local schools and churches, together with the political leadership need to coordinate primary prevention efforts against HIV/AIDS transmission. The media can be powerful in raising awareness, community activism, and mobilization of the masses at grass roots level by advocating behaviors that promote health. African leaders must indicate a strong political will by shaping policies that address HIV/AIDS. These leaders need resources (both internally and externally) to fund primary prevention programs that are community-based and outcome-oriented. PMID- 11760310 TI - HIV health crisis and African Americans: a cultural perspective. AB - While incidence of new HIV infections have decreased in the overall population, the numbers continue to rise in African-Americans creating a serious health emergency. Studies seem to imply that part of the rise is due to HIV beliefs and high risk behaviors among African Americans. Due to certain societal factors, African Americans appear to be at greater risk for contracting the virus. This article will examine these critical social factors and their impact on this current state of emergency in the African American community using Leininger's theory of Culture Care and Universality. Implications for health providers are also addressed. PMID- 11760311 TI - A four-phase program to recruit African American women into breast cancer promotion programs. AB - The author discusses a successful, nurse-coordinated collaborative community based breast health program that targeted older African American women from the state of South Carolina. Over 16 community organizations and health care partners supported the four-phase program that was funded by the South Carolina Breast and Cervical Risk Reduction Program and the South Carolina Chapter of the American Cancer Society. PMID- 11760312 TI - Health care breakdown: nurses are not to blame. PMID- 11760313 TI - The annual report: documenting organizational results. PMID- 11760314 TI - Challenging writer's block. How experienced authors make time to write. AB - Each of us can think of a thousand excuses why we can't write for publication. In reality each of these excuses is a writer's block that can be overcome. By using the tips described in this article, you will have the tools to conquer writer's block. With skillful planning you will be successful in publishing and the profession will benefit from your work. Just remember, once you see how nice your work looks in print, you won't be able to stop writing! PMID- 11760315 TI - Refining outlining skills. Part I: The topic or sentence method. AB - An outline is a plan for presenting the content and arranging it logically for the reader. While there are many ways to develop an outline, the ultimate goal is to identify the content to be covered and to organize it prior to beginning a draft. By using an outline, you have a basis for writing the draft, allowing you to focus on the content rather than on decisions as to organization. Remember, it is easier to revise an outline than the draft of an entire paper. PMID- 11760316 TI - Refining outlining skills. Part II: The computer method. PMID- 11760317 TI - Use of adult immunization strategies to increase the take of the influenza vaccine. A 2 year review. AB - 1. An actively involved multidisciplinary committee was one of the strongest aspects of the program. This strategy helped to fully integrate the program and provided a wider distribution network for information related to the program. 2. Flexibility in the availability of the vaccine yielded greater take rates than in prior years. Providing extra coverage to off shifts, coverage for unique scheduling formats, and making the influenza vaccine available within departments and off campus buildings were key to getting employees to accept the immunization. 3. The ability to use the knowledge of a diverse committee membership aided in better analysis of the mechanics of the process. Changes were made between years as the committee continued to assess successes and failures among different employee groups and addressed administration venues and incentives for staff. PMID- 11760318 TI - Mobile health units. Design and implementation considerations. AB - The decision to provide health care services with a mobile van is one which educational and service facilities are increasingly pursuing. The benefits include: The potential to increase the availability of services to underserved populations where access to care is perceived to be one reason for underuse of available services. The opportunity to increase and broaden the educational experiences of students in a training program. The opportunity to develop a sense of social responsibility in the health care provider. The process of deciding to pursue a van purchase is complicated, and administrators may best be served by obtaining experienced consultants to help them fully comprehend the issues involved. After the decision to purchase a mobile unit is made, it is necessary to focus on van requirements and design to meet federal, state, and city codes concerning motor vehicles and health requirements. Some modifications of one's standard practices are needed because of these codes. Being aware of them in advance will allow a smooth project completion. This article provides information about some of the steps required to implement a mobile unit. The approximate time from initial concept to van delivery was 1 year, with one fully dedicated project coordinator working to assure the project's success in such a short time frame. Seeing the gratified personnel and students who serve the children on the "Smiling Faces, Going Places" Mobile Dental Van of the NYUCD (see Figure 2), and knowing the children would otherwise not have received such services, allows the health care professionals involved to feel the development of this van is an exciting mechanism for delivery of health care to individuals who would otherwise go without. PMID- 11760319 TI - Behavioral risk management. A partnership between occupational health nursing and occupational psychiatry. AB - 1. The estimated prevalence of behavioral disorders among adults in the United States is 29.5%, affecting more than 52 million individuals each year. 2. Numerous or persistent problems in work performance increase the likelihood of either a psychiatric illness or unresolved psychosocial factors. Assessing work functions can help identify individuals early on with potential warning signs for employment problems. 3. Occupational health nurses can partner with occupational psychiatrists to clarify the complex scenarios that present to companies and recommend intervention. 4. Proactive intervention for employees, an effective team, and input and participation from the various stakeholders can produce positive outcomes for both the employee and the employer. PMID- 11760320 TI - Alternative and complementary therapies. PMID- 11760321 TI - Medical assessment units in the West Midlands region: a nursing perspective. AB - Within a 'whole system' approach to the management of acute medical referrals, many hospitals have introduced Medical Assessment Units (MAUs) to improve the care of acutely ill patients by assessing their need for hospital admission or discharge. This paper gives details of a research study designed to investigate the extent of MAU provision in the West Midlands Region, how these Units are organized and the nature of nursing roles within them. Results indicate that MAUs are organized and managed in different ways according to the likely length of patient stay. Likewise, nursing roles vary depending upon the context in which the nurses are working. PMID- 11760322 TI - Triage nurses' decisions using the National Triage Scale for Australian emergency departments. AB - The initiation of emergency care primarily depends on the decisions made by the triage nurse. Triage decisions can therefore have a profound effect on the health outcomes of patients who present for emergency care. If the National Triage Scale (NTS) was effective in providing a standardized approach to triage, a patient with a specific problem should be allocated to the same triage category, irrespective of the institution to which they present or the personnel performing the role of triage. This study examines triage nurses' level of agreement in their allocation of triage categories to patients with specific presenting problems using the NTS. Relationships between demographic characteristics of participants and triage decisions are examined and implications of any variation for triage practice and patient outcomes are explored. PMID- 11760323 TI - Assessment of head injuries in a minor injuries unit. AB - Approximately one million patients in the UK present to hospitals each year with head injuries. Almost half are under 16 years of age. (Royal College of Surgeons of England 1999). The majority of patients who attend for treatment will be suffering from a minor head injury. It is stated that some 92% of these patients will have normal neurology (Klauber 1993) and most will be discharged into the care of a responsible adult with instructions and advice for further observation at home. Only 1% of patients attending with a head injury have a skull fracture (Ramrakha & Moore 1997). The aim of this article is to guide the practitioner into ensuring a consistent, evidence-based approach to the assessment of patients with head injury when they present at a Minor Injuries Unit. This includes timely, appropriate referral for further investigation and clinical intervention. PMID- 11760324 TI - Research directions for specialist practice. AB - Emergency nursing is a specialist area of practice that demands particular knowledge and skills. This paper reports on a study to identify the research directions necessary to advance emergency nursing as a specialist area of practice. Nurses working in nine Australian hospital emergency departments responded to questions about current research practices, and the research priorities necessary to inform the development of knowledge and practice in the evolving specialty of emergency nursing. Forty-four core topics considered relevant to the knowledge base of emergency nursing were identified by nurses who were directly involved in providing patient care. The highest ranked topics were clustered into four priority areas for further research. The key areas for further research are education needs and opportunities, specialist roles of triage, trauma and practitioner, and nurses' coping mechanisms. Discussion of these topics is framed by the increasing specialisation of nursing practice, thus this paper aims to encourage consideration and debate about the research based development of the specialty of emergency nursing. PMID- 11760325 TI - Wound glue: a comparative study of tissue adhesives. AB - The purpose of this study was to determine which single-use wound adhesive is the most appropriate in terms of ease of use, minimal pain on application, adequate bonding time and wound closure. The three wound adhesives audited were Indermil (n-butyl cynoacrylate), Liquiband (n-butyl cynoacrylate) and Dermabond (octylcyanoacrylate). SAMPLE AND SETTING: The study was conducted in an urban paediatric emergency department treating over 39,000 patients annually. The sample was taken from the client population presenting with lacerations requiring tissue adhesive closure, within the limitations of the study (n = 63). METHODOLOGY: A non-blinded comparative study was performed. Children presenting with an appropriate laceration were assigned to receive either Indermil, Dermabond or Liquiband. The wounds were closed following the guidelines stated by the individual manufacturers. The nurses administering the tissue adhesive were asked to complete the audit form post closure and to comment on the procedure in descriptive terms. RESULTS: Scalp wounds accounted for 79% (n = 50) of all the lacerations closed in the study. None of the glues were reported to be completely pain-free. However, the Liquiband tissue adhesive produced an average pain score of only 0.1, whereas the Dermabond tissue adhesive scored the highest at 0.97. The nurses using the tissue adhesives reported that Liquiband was the best tissue adhesive in terms of wound closure and ease of use. However, the only tissue adhesive to report a 100% success rate was Indermil. DISCUSSION AND RECOMMENDATIONS: All of the tissue adhesives examined produced satisfactory results in terms of wound closure and ease of use. However, the Liquiband tissue adhesive produced the most consistent results, scoring higher in most of the categories when compared with the other tissue adhesives. PMID- 11760326 TI - Drug misuse at work. PMID- 11760327 TI - Scratching the itch: management of scabies in A&E. AB - Epidemics of scabies seem to occur in 20-25-year cycles. One of the resultant problems is that few A&E nurses practice through more than one epidemic and with each new outbreak of scabies, the latest generation of A&E nurses have to learn how to recognize and manage the disease. This article describes scabies, how to recognize it and the treatment options available. Although uncertainty remains, Permethrin is the first treatment of choice and should be used in the 5% cream form, not the 100% lotion. Crusted Norwegian scabies requires prompt and careful attention along with Specialist advice. The challenge for A&E staff is to recognize scabies, treat it appropriately and to help educate those most at risk. PMID- 11760328 TI - The advantages and disadvantages of Bier's blocks and haematoma blocks for Colles' fractures in A&E. AB - In the author's current area of practice the use of either the Bier's block or haematoma block for manipulating distal radial fractures seems to have been based mostly on the A&E consultant's preference. The purpose of this literature review was to determine if there was sufficient evidence on the advantages and disadvantages of each method of regional anaesthesia to advocate the general use of one and the exclusion of the other. When reviewing the literature the author specifically looked in to three key areas to answer this question: 1) the patient's perception of pain experienced during and after the manipulation; 2) patient safety i.e. the documented risks of the anaesthetic type used; and 3) the success of the manipulation as determined by repeat radiographs immediately after the application of a plaster of Paris cast. PMID- 11760329 TI - Transcribing in triage: the Wrexham experience. AB - The Manchester triage methodology and the practice of analgesic transcribing were introduced to the Accident & Emergency Department of the Wrexham Maelor Hospital in April 1998. The concept of nurse led transcribing is relatively new and its introduction was not without an element of administrative caution. The project was successfully implemented owing to the strategic input from a multidisciplinary group and elaborate steps towards quality assurance through audit. This paper describes the steps of implementation of this transcribing project and its successful completion through a prospective audit. Although there is a paucity of published literature in this topic, the Wrexham Pain Triage Group wishes to extend this implementation methodology into other areas of innovative nursing practice. PMID- 11760330 TI - The challenges of recruiting African American subjects and entry strategies used in northeast Ohio. AB - This article focuses on the recruitment of African American subjects because there are wide gaps in health outcomes within African American communities. Historical occurrences have contributed to the distrust of the motives of researchers about the purposes and credibility of research studies. Commonly acknowledged challenges include researchers' lack of sensitivity and understanding of minority subjects (Fujimoto, 1989; El-Sadr & Capps, 1992; Pletsch, Howe & Tenney, 1995). This paper discusses some of the challenges encountered by an African American researcher in North East Ohio in recruiting mothers and adolescent daughters, with and without a child, for a community-based communication intervention entitled: Mission Possible: Parents and Kids Who Listen (Riesch, Tosi, Thurston, Forsyth, Kuenning, & Kestly, 1993). This paper also suggests strategies and makes recommendations for researchers, who must recruit African American subjects. Researchers will need to examine their role in increasing the credibility of research within minority communities and develop innovative recruitment strategies. PMID- 11760331 TI - Comparison of independent and traditional registered nurse learners in a physical assessment course. AB - The purpose of this study was to determine if there was a significant difference in the time used to complete a neurological assessment by students who studied physical assessment and practiced independently when compared to students who used the traditional lecture method of instruction and practiced with the instructor. The research methodology utilized a descriptive comparative design. The convenience sample consisted of 20 Registered Nurses (RNs) randomly selected from a class of 34 RN students in one section of an undergraduate Physical Assessment course. A watch was used to measure the time the student used to complete the neurological assessment. A one-tailed independent samples t-test was used to compare the difference in time used as indicated by the means of the two groups. The level of significance was 0.05. The result of the study is that there was no significant difference found between the two groups on the amount of time used to complete a neurological assessment p > .05, t = 1.151, p = .303. The conclusion of this study was that RN students are able to learn physical assessment independently and successfully complete a neurological assessment in a similar amount of time as RN students who use the traditional classroom method. Recommendations include replicating the study with a larger sample and with students in a Graduate Health Assessment course to determine if similar results will occur. PMID- 11760332 TI - Adult sickle cell patients' perceptions of nurses' caring behaviors. AB - Sickle cell disease (SCD) is a life-long, acutely painful, chronic illness. This study was conducted to explore differences in perceptions of nurses' caring behaviors between adults with SCD and adults with general medical conditions and the differences in perceptions of nurses' caring behaviors between men with SCD and women with SCD. Watson's (1988) Theory of Human Caring provided the conceptual framework. In this descriptive, correlational design, convenience sampling was used to obtain 29 adults with SCD and 34 adults with other medical conditions. The mean age for adults with SCD was 35.8, and on average they reported four hospitalizations per year. The mean age for the general medical patients was 48.9, and they averaged two hospitalizations per year. Instruments used in this study were a demographic data form and the Caring Behavior Assessment, modified for use in this study. The instruments were distributed through support groups using the snowball technique. Data were analyzed using descriptive statistics and independent t-tests. Participants with SCD reported lower satisfaction with nurses' caring behaviors than those with other medical conditions (t = 2.19, p = .03). Women with SCD reported lower satisfaction with nurses' caring behaviors than men with SCD (t = 2.91, p = .01). PMID- 11760333 TI - [Penetrating injuries of the trunk]. PMID- 11760334 TI - [Penetrating trauma of the trunk]. AB - Trauma has been described as a "disease of bleeding" [45]. Recognition of acute blood loss after injury, and restoration of homeostasis is the cornerstone of the initial care of the badly injured patient. Hypovolaemia remains the most common cause of death among those killed in action during military conflicts [46] and, in the civilian arena, increasing numbers of patients are being encountered with penetrating injuries, even in societies where blunt injury have previously been the norm. Increased use of higher calibre weapons or with altered ammunition means some patients will present with exsanguinations and critical physiological instability. Successful outcomes after the treatment of patients with penetrating trauma depend on the integration of many agencies, from prehospital care, initial reception, assessment and resuscitation through the operating room, intensive care and post-injury rehabilitation. Recognition of the importance of time and adherence to sound trauma management principles with conservative management when appropriate should see further improvements in our treatment of this important group of patients. Reducing the incidence of these injuries is the responsibility of us all and must be the focus of all governmental initiatives. PMID- 11760335 TI - [Continuous stroke volume monitoring as "hemodynamic online monitoring" in polytrauma intensive care patients: technically possible--clinically necessary?]. AB - PURPOSE: Is the measurement of continuous cardiac output useful for the management of polytrauma patients? METHODS: In a prospective non randomized study (ethic commission file 43/96) we evaluated the diagnostic and therapeutic impact of the CCO (continuous cardiac output measurement) for polytrauma patients on the ICU. The Baxter Vigilance System was used for measuring the continuous cardiac output. The CCO values were controlled once a day by the conventional "cold" thermodilution technique. RESULTS: All values are given as mean +/- standard deviation. The Patients were scored on the first day for ISS (injury severity score) (47 +/- 17) and APACHE II (15 +/- 5). The CCO was used no later than 12 hours after the initial treatment in 20 polytrauma patients. As clinical outcome parameters were chosen: days on ventilation (23 +/- 23 days), days on the ICU (31 +/- 26 days) and mortality (20%). The treating ICU physicians were asked in a standardized questionnaire, whether or not there was an impact of the CCO measurement on their therapy. Seven different surgeons were working with the system. CONCLUSION: The unique opinion was that the CCO device had an impact on their decision making in the fluid and drug management of the study patients. Our first experience, however, suggests that this device may become an important improvement in the management of haemodynamics in the early trauma phases. Before a wide-spread application of this method on the ICU an evidence based prospective randomized trial should be performed. PMID- 11760336 TI - [Constant Score and Neer Score. A comparison of score results and subjective patient satisfaction]. AB - INTRODUCTION: The Constant- and the Neer-Score are widely used to assess shoulder function after trauma or shoulder diseases. The objective of this study was to compare the correlation of score result with the patient subjective assessment. We hypothesized that there is a clinically relevant difference between the score result and the patient assessment, especially for highly selective patient groups. METHODS: 51 patients were followed up after the surgical treatment of a proximal humeral fracture. For each patient the Constant- and the Neer-Score was calculated. Further, the patients were asked for a subjective assessment of their shoulder function ("excellent", "good", "fair", "poor"). RESULTS: For both score systems a good linear correlation (r = 0.97) is shown. 57% of the patients assessed their shoulder function as "excellent" or "good", but only 37% (Constant) vs. 43% (Neer) of the patients were classified as "excellent" or "good" based on their score results. The Spearman correlation of subjective and score-based assessment was just fair with r = 0.50 (Constant) and r = 0.55 (Neer). When comparing the score results with the patient subjective assessment for the groups: "excellent", "good", "fair" and "poor", there was a positive correlation for the Neer-Score in 20 cases and for the Constant-Score in 15 cases. Of all elderly patients (> 60 years, n = 20), 14 (Neer-Score) vs. 16 (Constant-Score) assessed their shoulder function as better than the score did. CONCLUSION: The hypothesis of a clinically relevant difference between the subjective and the score-based assessment of shoulder function can be confirmed. Our results suggest that for clinical practice, statements and therapy strategies recommended in the literature, that are just based on score results might not be valid for all patient-groups (e.g. elderly patients). PMID- 11760337 TI - [Repositioning femoral neck fracture in younger patients. Valgus or anatomic reposition?]. AB - In a retrospective study, 51 patients with femoral neck fractures received open reduction and internal fixation. They were divided into two groups. Group A included all patients treated with anatomical reduction. In Group V, the bone fragments were positioned in > or = 5 degrees valgus. The median age of the patients was 37.4 years (range 13-58). 51 patients were available for follow-up assessment at 10.1 (+/- 4.3) years. There were 33 patients in Group A and 18 in Group V. All patients were examined with regard to early and long-term complications. In the first five years, avascular necrosis was seen in 18% in Group A and not at all in Group V. Nonunion occurred in 9% of Group A and 5.5% of Group V. On average at 10 years after the operation, coxarthritis (Kellgren 2) was evident in 21.2% of Group A and 55.6% of Group V (p = 0.04). According to the Hip-Score of Merle d'Aubigne, the patients treated with anatomical reduction had a better functional outcome after 10 years. With respect to the results we recommend in younger patients (< 60 years) anatomical reduction in Pauwels I and Garden-II-fractures. Valgusreduction should be performed as well in Pauwels II and III as Garden-III-and-IV-fractures. PMID- 11760338 TI - [Developments in hip hemi-arthroplasty and theory of the link-chain dimeric hip prosthesis]. AB - Aim of the study was to analyze the developments of hemiarthroplasties from the femur prosthesis to the bicentric bipolar prosthesis of today. Using the theories published 1990 by Nagerl about "dimeric link chains", nineteen bipolar-head systems were analyzed and biomechanically explained. Clinical findings, such as the problems of luxation and varus positioning of the monocentric bipolars, as well as the valgus, "self-centric" positioning of the bicentric prosthesis are discussed and explained correctly by physics. The hemiarthoplasty with the bicentric bipolar system of today has realized the principles of the dimeric link chains and is superior concept. Eleven of the sixteen today available systems work like this concept which was reached by try and error. The function of a bicentric system is solved now and explained by physics. PMID- 11760339 TI - [External ear injuries--classification and therapeutic concept]. AB - The treatment of traumatic defects of the auricle concerning the exact reconstruction of details and aesthetic aspects is exacting for the surgeon. To face the expectations towards best trauma care, the different locations and extent of auricular injuries should be included in the different therapeutic strategies. The insufficient treatment results in mostly difficult secondary conditions. We present a classification for ear traumas, which considers size and location of defects. Depending on this, different techniques and methods of reconstruction are recommended. Advantages and disadvantages are pointed out and discussed with several examples and with the present literature. PMID- 11760340 TI - [Precision analysis of navigation-assisted implanted thoracic and lumbar pedicled screws. A prospective clinical study]. AB - A prospective clinical trial was performed to study the accuracy of pedicle screw placement of consecutive computer-aided and conventional techniques. Concerning the clinical performance of the navigation system, the average time of matching has been 8.4 minutes per vertebrae. For evaluation of the results, only complete intraosseous placement of the pedicle screw has been defined as correct position. Any medial or lateral perforation of the cortical structure of the pedicle was recorded as malplacement. In the CT-controlled patients complete intrapedicular placement of the screw was obtained in 36 of 45 thoracic (80%) and in 22 of 27 navigated lumbar (81%) pedicles. In the conventional cohort group 27 of 34 (79%) thoracal and 43 of 52 (83%) lumbar screws were completely in. No radicular neurologic damage, caused by a malplaced transpedicular screw has been observed in both groups. In the presented study is shown, that the application of the computer-assisted freehand navigation can improve results concerning the precision of spinal screw placement. Although, the spinal navigator has to consider a learning curve for the clinical inauguration of the system and the qualification of the implant system for computer-assisted application. PMID- 11760341 TI - [Principles and techniques of primary trauma surgery management at the site]]. PMID- 11760342 TI - [Traumatic aortic rupture in ankylosing spondylitis--a fatal complication]. AB - Fractures of the spine represent a severe complication particularly in patients with ankylosing spondylitis because of high morbidity and mortality. We report on a patient with a hyperextension fracture of the lumbar spine, leading to disruption of the aorta and caval vein. PMID- 11760343 TI - [Percutaneous tibiotalar arthrodesis]. AB - We report on a 50-year-old female patient with bimalleolar fracture and subsequent posttraumatic arthrosis who was treated by minimally invasive nonresection tibiotalar compression arthrodesis using internal fixation and cancellous bone grafting. The advantages of this technique include minimal exposure of tissues, good control of the relationship between the tibia and the talus, and short hospital stay. PMID- 11760344 TI - [Congenital diaphragmatic hernia in a polytrauma patient]. AB - A case of congenital, bilateral, diaphragmatic hernia in a patient with multiple trauma after a motor accident is presented. No anamnestic information was available because of the need for intubation at the accident site. After the insertion of bilateral chest tubes because of left sided pneumothorax and right sided haematopneumothorax a mediastinal mass became apparent. A CT scan revealed a bilateral diaphragmatic hernia. Problems and therapy of this condition as well as differentiation between congenital and traumatic hernias are discussed in this case report. A mediastinal mass of unknown origin in multiple trauma patients suggests the presence of traumatic diaphragmatic hernia. Diagnostic signs suggesting congenital hernia as compared to acute traumatic hernia are: unilateral or bilateral localisation in the dorsal muscular part of the diaphragm and non-suspicious appearance of parenchymal abdominal organs in relation to the size of the hernia. Diaphragmatic hernias reduce the vital and functional residual capacity of the lungs, possibly leading to respiratory complications and infections. PMID- 11760345 TI - [Urothelial carcinoma]. PMID- 11760346 TI - [Prognostic factors in urothelial carcinoma]. AB - Intense efforts are being made to identify prognostic markers in superficial and muscle invasive bladder cancer in order to get more detailed information on the biological properties of urothelial cancer. Tumor associated antigens, angiogenetic factors and their inhibitors, cell adhesion molecules, cell cycle regulating genes and proteins, oncogenes and tumor suppressor genes are subjects of clinical investigations. This article provides a contemporary review of prognostic factors in bladder cancer and their possible clinical implication. A better characterization of urothelial cancer can be anticipated from new technologies allowing analysis of multiple genes or gene products in an automated one-step procedure. PMID- 11760347 TI - [Etiopathology, risk factors, environmental influences and epidemiology of bladder cancer]. AB - The etiology of bladder cancer is well investigated. Bladder carcinogenicity of nitrosamines is proven in animals but not in men, although dimethylnitrosamine in urine of patients with urinary infections or bilharziosis suggest a causative role. Aromatic amines are strong bladder carcinogens. Arsen is proven to be bladder carcinogenic as well as the nitrofurane FANFT. Nitrofurantoin however is not bladder carcinogenic nor are the endogenous metabolites of tryptophan. The influence of papilloma virus on bladder carcinoma induction ist not definitely proven yet. Bilharziosis or chronic urinary infections correlate with bladder carcinomas, nitrosamines being the possible reason. The reason for the increased incidence of bladder carcinomas in balkan nephropathy ist not clear. Arcolein as a metabolite of Cyclophosphamid is a strong bladder carcinogen as well as Phenacetin. Immune suppression and radiotherapy are risk factors, too. About 50% of bladder carcinomas are due to cigaret smoking. PMID- 11760348 TI - [Diagnostic algorithm of urothelial tumor of the upper urinary tract]. PMID- 11760349 TI - [Therapy of carcinoma of the kidney pelvis]. AB - Transitional cell carcinoma of the renal pelvis is relatively uncommon, and only 5% of all urothelial carcinomas occur in the renal collecting system. Invasive tumors are often aggressive in their biological behavior and show a high tendency for systemic progression. Conservative therapy should only be considered an option in patients with imperative indications (solitary functioning kidney, bilateral tumor, renal insufficiency). In some cases, organ-sparing techniques such as open resection or endourological treatment (percutaneous or by ureteroscopy) can be performed. However, nephroureterectomy with excision of a bladder cuff is considered to be the standard treatment and should be performed whenever possible. PMID- 11760350 TI - [Therapy of ureteral tumor]. AB - Nephroureterectomy is the standard treatment of tumors in the upper and middle third of the ureter. Whereas, resection of the distal ureter and uretercystoneostomy is the treatment of choice of tumors in the lower third, as long as there is enough renal function which is worthwhile to be preserved. Lymphadenectomy should be performed in all patients suspicious for invasion of the ureteral wall since already 10% of patients with pT1 and pT2 tumors will present with metastases to the lymphnodes. In case of functional or anatomic single kidney therapy has to be adapted to the patient and tumor appropriately. Endoscopic resection, partial or complete resection of the ureter with substitution by ileum or autotransplantation with pyelovesicostomy are the operative options. Elective endoscopic treatment of ureteral tumors should be done in patients with G1 tumors only. However, the recurrence rate is as high as 30 to 60% and the mean interval to recurrence is about 9 months. Regular followup by means of cytology and endoscopy is mandatory. Laparoscopic nephroureterectomy is still a experimental treatment at present time and should be not considered in the treatment of ureteral tumors because of the complexity of the procedure and the risk of tumor spillage. PMID- 11760351 TI - [Treatment of superficial bladder tumor]. AB - Every year in Germany approximately 12,000 people are afflicted by superficial carcinoma of the urinary bladder. In addition, the number of recurrences is not inconsiderable. The goal of optimal therapy, therefore, is not only to cure the patients but also to lower the high rate of recurrence by appropriate prophylaxis. After transurethral resection, treatment options include various topical modalities of instillation therapy, e.g., chemotherapy or immunotherapy. The individual decision on which treatment modality is chosen should be based on the risk of relapse and the progression of the tumor. This depends on tumor stage, degree of differentiation, and the presence of recurrence. Some treatment options, such as instillation of bacillus Calmette-Guerin, have been validated by large randomized studies in the sense of evidence-based medicine. PMID- 11760352 TI - [Locally advanced or metastatic bladder carcinoma. Current aspects of therapy]. AB - The prognostic factors for infiltrating tumors established by the TNM system in 1997 include: Depth of infiltration, degree of differentiation, status of lymph nodes distant metastases. Of the additional factors investigated, only tumor size and hydronephrosis appear to be of prognostic significance. In the scope of molecular markers, the loss of expression of the epithelial cell-cell adhesion molecule E-cadherin signals an unfavorable clinical course. In cases of carcinoma of the urinary bladder without metastases (T2-4,N0,M0), radical cystectomy is the therapy of choice. A preceding neoadjuvant systemic regimen of chemotherapy with three cycles of M-VAC (methotrexate, vinblastine, adriamycin, cisplatin) significantly improves the survival rate. In patients with locally advanced urinary bladder carcinoma, however, adjuvant systemic chemotherapy with M-VAC after cystectomy and lymphadenectomy offers no advantages for survival. Quality of life in patients with metastatic bladder cancer disease is improved by new cytotoxic drugs, i.e. gemcitabine or taxanes. PMID- 11760353 TI - [Urinary drainage and urinary diversion. Patient selection and counseling]. AB - In the past 18 years, traditional methods of urinary drainage and diversion via conduits and ureterosigmoidostomy have been increasingly replaced by new techniques of orthotopic bladder substitution and continent urinary diversion. With growing knowledge of the physical and physiological relationships, the more than 40 techniques of continent urinary diversion using almost all segments of the gastrointestinal tract have ceased being spectacular and experimental. The various methods are well established, preparatory care and follow-up are standardized, and the technical and methodological aspects are sufficiently elucidated so that the underlying precept, i.e., improvement of these patients' quality of life, has priority. PMID- 11760354 TI - [Treatment of metastases of urothelial carcinoma. Results of a prospective study of metastases surgery]. AB - We initiated a prospective phase II trial to assess the outcome of complete surgical removal of metastases from bladder cancer with regard to survival and quality of life. Between 1995 and 1999, 70 patients (52 males, 18 females) with a median age of 64 years (range: 30-88 years) were treated with surgical complete resection of bladder cancer metastases. Patients with asymptomatic (n = 19) and symptomatic (n = 51) secondary metastases from bladder cancer refractory to methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy were included. We removed secondary metastases in lymph nodes (63%), peritoneum (10%), skin (3%), bone (3%), lung (15%), and liver (6%) and measured survival and performance scores. The median survival time was 7 months. With a 1-year survival rate of 30% and a 2-year survival rate of 19%, the prognosis is unfavorable independent from the site of metastasis. However, 83% (42 of 51) of the patients with symptomatic secondary metastases did benefit from surgery regarding quality of life, e.g., performance score, and we assessed an improvement in the WHO performance score from 3.3 to 2.1 (p = 0.005). Surgical removal of metastases from bladder cancer refractory to systemic therapy has an impact on quality of life limited to patients with symptomatic disease. PMID- 11760355 TI - [Palliation of urothelial carcinoma of the bladder]. AB - Bladder cancer is a disease that occurs late in life (> 50% of the patients in Germany are 70 years or older). The general condition of the patients is frequently reduced, aggressive therapy of advanced tumours stages is therefore often contra-indicated. In this situation, palliative treatment is of extraordinary importance. Strangely enough, controlled prospective trials are lacking. They are, however, necessary in order to establish, or improve, standards of palliative treatment. Several smaller studies proved the potential of bladder irrigation and the embolisation of A. iliaca to stop bleeding from the tumourous bladder. If the tumour causes urinary retention, a permanent ureteral stent may in certain cases help to guarantee adequate flow. The assessment of palliative radiotherapy is not possible due to small numbers of (and highly selected) patients. It may have a potential in cases of hematuria, pain, and incontinence. New anti-tumour agents (e.g. Gemcitabine) may turn out to be a tolerable and effective palliative. PMID- 11760356 TI - [After-care of bladder carcinoma]. AB - The present article offers an introduction to the aftercare of patients with carcinoma of the urinary bladder. These recommendations are based on the guidelines of the German Association of Urology and the European Association of Urology. Aftercare always depends on the risk of recurrence and progression of the primary tumor and the extent of the therapy applied. Thus, after transurethral resection of a superficial carcinoma of the urinary bladder, aftercare focuses on follow-up cystoscopy. Radical cystectomy of the muscle invading and locally advanced carcinoma should be followed by extensive examinations, including computed tomography of the pelvis and the abdomen. In addition, the various forms of urinary diversion after cystectomy with its specific late complications should be included in the aftercare. Moreover, the psychological significance of the follow-up examinations should not be neglected. PMID- 11760357 TI - [Laparoscopic liver donor nephrectomy. Personal experiences and review of the literature]. AB - Despite improved success rates, the number of kidney transplantations in Germany in the last few years has stagnated, resulting in increasing waiting lists of patients on dialysis. In Germany, only 16.7% of kidney transplantations are living-donor nephrectomies, representing a relatively low rate compared to other countries (The Netherlands 28%, Sweden 35%). Since April 1998, we have performed ten retroperitoneoscopic living-donor nephrectomies (six left, four right side). The mean operating time was 216 min (155-290) with minimal blood loss. No intraoperative complications were observed. Warm ischemia time amounted to a mean of 4 min (2-7). The mean cold ischemia time was 165 min (76-290). Postoperative hospital stay of the donors was 6 days (4-10). All transplants functioned immediately; mean serum creatinine dropped from initially 8.0 mg/dl (5.3-11.5) on day 1 to 1.4 mg/dl (0.9-1.6) 3 months after surgery. This did not differ from previously operated open donor nephrectomies. An analysis of the literature included data of 4240 patients from 25 publications between 1980 and 2000 reporting on either open or laparoscopic living donor nephrectomies. PMID- 11760358 TI - [Urologic tumors and organ transplantation. Recommendations of the Kidney Transplantation Working Group of the Ongoing Graduate and Continuing Education Committee of the German Society of Urology]. PMID- 11760359 TI - [Diagnosis of congenital dilatation of the urinary tract. Consensus Group of the Pediatric Nephrology Working Society in cooperation with the Pediatric Urology Working Group of the German Society of Urology and with the Pediatric Urology Working Society in the Germany Society of Pediatric Surgery]. PMID- 11760360 TI - [Guideline for diagnosis and therapy of genital diseases caused by human papillomaviruses (HPV). Guideline of the German Society of Urology]. PMID- 11760361 TI - Progress towards poliomyelitis eradication, WHO Eastern Mediterranean Region. 1 January 2000-30 September 2001. PMID- 11760362 TI - Criteria used in compiling the infected area list. PMID- 11760364 TI - Physician group practices are steadily becoming standard fare. PMID- 11760363 TI - 2001 physician data survey on practice characteristics. Part II. PMID- 11760365 TI - Fair ways to figure who gets paid how much. PMID- 11760366 TI - Smallpox and anthrax vaccine information. PMID- 11760367 TI - Like Russian roulette, ecstasy is a game of life or death. PMID- 11760368 TI - Advocating the views of medicine in the appellate courts. PMID- 11760369 TI - Role of urbanization and air pollution in adolescent asthma: a mass screening in Taiwan. AB - BACKGROUND AND PURPOSE: The prevalence of asthma in school children in Taiwan is increasing. This study used mass screening among middle school children in Taiwan to determine the prevalence of asthma and related factors. METHODS: Data were collected from parents using a self-reported questionnaire and from children using the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire. Six study teams conducted the survey nationwide in 1995-1996, with the assistance of middle school nurses and teachers. RESULTS: Among the 1,018,031 students at 795 middle schools who returned questionnaires, 8.5% had a history of asthma (ranging in prevalence from 4.2% to 13% in 25 areas). The prevalence of asthma was higher in boys than in girls (10.0% vs 7%) and was highest in more urbanized areas (11.2%), followed by moderately urbanized areas (7.4%) and less urbanized and rural areas (6.5%). Controlling for age, family smoking, family incense burning, and parental education level, multivariate logistic regression models indicated that children living in an area with heavy air pollution were more likely to have asthma than those in an area with no or light pollution (odds ratio, OR = 2.01 and 95% confidence interval, CI = 1.94-2.09 based on parental ranking of pollution level, or OR = 1.30 and 95% CI = 1.18-1.42 based on pollution level reported by the Environmental Protection Administration). CONCLUSIONS: Adolescent asthma in Taiwan is most prevalent in the most urbanized areas and decreases in prevalence in less urbanized areas. This study also found that higher parental education level and higher area air pollution were associated with higher adolescent asthma prevalence. PMID- 11760370 TI - Risk factors for ICU mortality in critically ill patients. AB - BACKGROUND AND PURPOSE: Advances in critical care medicine have increased the chances of survival for patients with severe illness or trauma. However, such patients consume a large proportion of medical resources. This study sought risk factors for mortality that have potential to be modified among patients treated in medical or surgical intensive care units (ICUs). METHODS: This 6-month prospective observational study was conducted in the medical and surgical ICUs of an 1,800-bed university hospital. All adult patients with an expected ICU stay of 48 hours or more were followed up regularly until discharge from the ICUs, or for 10 weeks during their stay in ICUs. RESULTS: Of 342 patients enrolled, 77 (22.5%) died during a median follow-up period of 5 days (range, 2-70 days). Among a range of variables at the time of ICU entry or developing during stay in ICUs, 17 were associated with higher mortality rate. Multivariate analysis using a logistic regression model demonstrated that the presence of systemic inflammatory response syndrome (SIRS) at the time of ICU entry (adjusted relative risk, ARR, 2.85; 95% confidence interval, CI, 1.16-7.05), Acute Physiological and Chronic Health Evaluation (APACHE) II score on ICU Day 4 (ARR 1.12 with increment of one score; 95% CI 1.01-1.24), Therapeutic Intervention Scoring System (TISS) score on Day 4 (ARR 1.13 with increment of one score; 95% CI 1.05-1.23), parenteral nutrition (ARR 4.97, 95% CI 1.73-14.26), and nosocomial Candida infection (ARR 3.39, 95% CI 1.12-10.23) were independently associated with ICU mortality. CONCLUSIONS: In addition to SIRS and the APACHE II and TISS scores, this study found that nosocomial Candida infection and parenteral nutrition were independently associated with mortality after control for admission conditions, severity of illness scores, and interventions. PMID- 11760371 TI - Prolonged interferon treatment after combination interferon and ribavirin therapy in patients with chronic hepatitis C: a clinical trial of interferon relapsers and non-responders. AB - BACKGROUND AND PURPOSE: For the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy, the efficacy of combination therapy with interferon alfa plus ribavirin is superior to interferon alone. The aim of this study was to determine whether prolonged interferon alfa treatment after 24-week combination therapy can further increase the efficacy of combination therapy. METHODS: Nineteen interferon relapsers and 17 interferon non-responders were randomly assigned to receive either interferon alfa 5 million units (MU) thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks (regimen A) or interferon alfa 5 MU thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks followed by interferon alfa 3 MU thrice weekly for another 24 weeks (regimen B). Efficacy was assessed by normalization of serum aminotransferase concentrations and disappearance of serum hepatitis C virus (HCV) RNA at the end of treatment and at 24 weeks after stopping treatment. RESULTS: Overall, 67% of relapsers receiving regimen A and 80% of those receiving regimen B had sustained virologic responses 24 weeks after stopping treatment. In contrast, 45% of non-responders receiving regimen A and 63% of those receiving regimen B had sustained responses. The sustained response was more common in relapsers with non-1b HCV genotypes. The sustained response rate to combination therapy was 50% or more in patients with genotype 1b infection. CONCLUSIONS: Prolonged interferon treatment after combination therapy has a comparable efficacy to combination therapy alone for the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy. PMID- 11760372 TI - Incidence and predictors of isolated systolic hypertension and isolated diastolic hypertension in Taiwan. AB - BACKGROUND AND PURPOSE: The significance of isolated systolic hypertension (ISH) has been well documented, particularly in the elderly. However, isolated diastolic hypertension (IDH) has not been formally recognized as a unique hypertension entity. This study compared the ages of onset and characteristics of ISH and IDH. METHODS: The Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) is an ongoing longitudinal study of the risk factors for and pathogenesis of cardiovascular disease in two Taiwanese townships, Chu-Dung (a Hakka community) and Pu-Tzu (a Fukienese community); participating patients were included in our study. Among the 3,357 subjects who were aged at least 20 years, free of hypertension, and had complete data at baseline, 2,374 subjects were followed. The average duration of follow-up was 3.23 years and the follow-up rate was 71%. Data regarding smoking, alcohol consumption, health and socioeconomic background, blood pressure, and body mass index were collected. Clinical and hemostatic profiles were assessed. RESULTS: ISH (systolic blood pressure, SBP > or = 140 mmHg and diastolic blood pressure, DBP < or = 90 mmHg) incidence increased with age in general (men: 0 per 1,000 person-years at age 20-34 yr, 1.9 at age 35-49, 14.3 at age 50-64, 40.9 at age 65-74, and 73.3 at age 75+ yr; women: 0 per 1,000 person-yr at age 20-34 yr, 3.6 at age 35-49, 17.8 at age 50 64, 64.9 9 at age 65-74, and 33.5 at age 75+ yr), but peak incidence of IDH (DBP > or = 90 mmHg and SBP < or = 140 mmHg) occurred between 35 and 49 years (men: 8.9 per 1,000 person-yr at age 20-34 yr, 14.5 at age 35-49, 12.3 at age 50-64, 2.7 at age 65-74, and 0 at age 75+ yr; women: 1.7 per 1,000 person-yr at age 20 34, 4.2 at age 35-49, 3.7 at age 50-64, 0 at age 65-74, and 0 at age 75+ yr). Significant predictors for ISH were older age (men: hazard ratio, HR = 8.25 at 45 64 yr and HR = 22.91 at 65+ yr; women: HR = 34.11 at 45-64 yr and HR = 97.98 at 65+ yr), diabetes (HR = 2.57) and elevated fibrinogen (HR = 1.49) in men, and shorter clotting time in women (HR = 1.23). Significant predictors for IDH were elevated body mass index (men: HR = 4.03; women: HR = 7.4), and higher glucose (HR = 1.46) and uric acid concentrations (HR = 1.94) in men. CONCLUSIONS: The results of this study indicate that ISH and IDH have different age incidence patterns and predictors, and suggest that the pathogenesis of ISH and IDH may be different. PMID- 11760373 TI - Factor structure and explanatory variables of the Mini-Mental State Examination (MMSE) for elderly persons in Taiwan. AB - BACKGROUND AND PURPOSE: The Mini-Mental State Examination (MMSE) is commonly used in studies and clinical assessment of cognitive functioning. The purpose of this study was to examine the factor structure and variables explaining the scores of the MMSE in elderly persons in Taiwan, in order to provide a reference for instrument selection and data collection for clinicians and researchers. METHODS: Secondary data from an epidemiologic study that included 1,442 randomly selected subjects aged 64 to 98 with an average age of 72.6 years were used. Males comprised 57.1% of the sample, and females 42.9%. Exploratory and confirmatory factor analysis and covariance structure modeling were used to analyze the data. RESULTS: In the cross validation of the covariance structure modeling, 50.1% of the variance in simple processing, 86.9% in complex processing, and 66.9% in memory/attention were explained. Better education background predicted better score in complex processing ability (path coefficient = .860). Greater independence in self-care ability predicted better scores in simple processing (path coefficient = -.716) and memory/attention (path coefficient = -.811). CONCLUSION: The results of this study indicate that items in the MMSE measuring complex processing ability including writing, reading and obeying, and copy design are seriously biased by educational background, and that the remaining items are better indicators of the subject's cognitive functioning for elderly persons in Taiwan. In our model, self-care ability was strongly related to cognitive functioning as measured by the MMSE, especially for items in the factors of simple processing (registration, naming, repetition, and commanding) and attention/memory (orientation to place and time, attention, and recall). PMID- 11760374 TI - Epidemiologic study of the prevalence and severity of myopia among schoolchildren in Taiwan in 2000. AB - BACKGROUND AND PURPOSE: A nationwide survey was performed in 2000 to determine the prevalence and severity of myopia among schoolchildren in Taiwan and to compare these findings with the results of the last survey performed in 1995. METHODS: We first divided the whole island into regions according to developmental grade scores and then sampled with the probability proportional to the size of the population within each stratum. A total of 10,889 students were enrolled, including 5,664 boys and 5,225 girls, with ages ranging from 7 to 18 years. The refractive status and corneal radius of each student were measured with an autorefractometer under cycloplegia and checked with retinoscopy. Axial length was measured using biometric ultrasound. RESULTS: The myopia rate increased from 20% at 7 years, to 61% at 12 years, and 81% at 15 years. A myopic rate of 84% was found for schoolchildren aged 16 years through 18 years. The mean refractive index reached myopic status at the age of 8, and increased to -4.12 D in girls and -3.15 D in boys at the age of 18 years. The prevalence of high myopia (> -6.0 D) at the age of 18 years was 24% in girls and 18% in boys. The increase in axial length corresponded with the progression of myopia. The anterior chamber depth was slightly deeper from 7 years to 13 years and then remained stable. The lens thickness decreased from 7 years to 11 years. After age 15, further thickening of the lens was correlated with both age and severity of myopia. However, the corneal curvature was not related to age or severity of myopia. Girls had a higher prevalence and more severe degree of myopia than boys. Children in urban areas had a higher prevalence and more severe degree of myopia than children in rural areas. CONCLUSION: The prevalence and severity of myopia in schoolchildren in Taiwan in 2000 increased compared to 1995, with the most severe increases occurring in younger age groups. Thus, preventing schoolchildren developing myopia at a young age may slow down the increase in severity of myopia in Taiwan. PMID- 11760375 TI - CD34+ stem cell transplantation in malignancies: report of three cases. AB - Purging tumor cells from peripheral blood stem cells (PBSCs) used to treat patients with malignancy is important in the prevention of relapse. Positive selection of CD34+ stem cells using either immunomagnetic methods or an avidin biotin conjugated CD34 monoclonal antibody binding column can reduce the number of contaminating tumor cells. We describe the management of three patients with malignancy treated using high-dose chemotherapy and enriched CD34+ cell transplantation. PBSCs were mobilized with cyclophosphamide plus recombinant granulocyte-colony stimulating factor (rG-CSF), and then leukophoresis was performed to harvest the PBSCs. The collected cells were positively selected for CD34+ cells using the Cellpro system. The CD34(+)-enriched PBSCs were then cryopreserved in the vapor phase of liquid nitrogen for future reinfusion. All three patients recovered smoothly after transplantation. The mean time to full hematologic recovery was 12 days for white blood cells (> or = 1 x 10(9)/L) and 14 days for platelets (> or = 20 x 10(9)/L), respectively. Partial remission occurred in two patients who were disease free for more than 4 years, and in one patient who died of hepatic failure with liver cirrhosis 5.5 months posttransplantation. PMID- 11760376 TI - Meningitis due to penicillin-resistant Neisseria meningitidis in a 20-year-old man. AB - The emergence of meningococcal strains with reduced susceptibility to penicillin has been reported in several countries during the past two decades, but not in Taiwan. We report a case of meningococcal meningitis with intermediate resistance to penicillin. A 20-year-old male soldier complained of chills, fever, and headache for 2 days, followed by drowsiness. Physical examination revealed erythema of the pharynx, stiff neck, erythematous maculopapules, and petechiae over the trunk and four limbs including palms and soles. Analysis of the cerebrospinal fluid (CSF) showed a white blood cell count of 9.06 x 10(6)/L, a glucose concentration of 0.165 mmol/L, and a protein concentration of 7.85 g/L. CSF culture yielded Neisseria meningitidis, serogroup B. The minimum inhibitory concentration of penicillin was determined using an E-test (0.125 microgram/mL); there was no beta-lactamase production. He recovered after high-dose penicillin G treatment with six doses of 24 million units per day for 11 days. The emergence of penicillin resistance in N. meningitidis in Taiwan requires surveillance. High dose penicillin may be successful in treating penicillin-insensitive meningococcal meningitis. Alternative treatment with third-generation cephalosporins should be considered if poor response to penicillin is encountered. PMID- 11760377 TI - Pneumocystis carinii pneumonia in systemic lupus erythematosus: a report of two cases. AB - Patients with systemic lupus erythematosus (SLE) have increased susceptibility to infection by Pneumocystis carinii, but this condition has rarely been reported in Taiwan. Here, we describe two cases of patients with SLE who developed Pneumocystis carinii pneumonia (PCP). The first patient was a 39-year-old woman presenting with fever and dyspnea that had lasted 2 weeks. Chest roentgenography disclosed bilateral interstitial and alveolar infiltrates. The second patient was a 22-year-old woman presenting with a 4-day history of malaise, cough, dyspnea, and fever. She had concomitant Mycobacterium tuberculosis infection. Both patients had been treated with varying doses of corticosteroids and/or cytotoxic drugs within 4 months before presentation. Diagnosis was established based on the findings of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). Both patients received trimethoprim-sulfamethoxazole (20 mg.kg-1.d-1 trimethoprim), but finally died of nosocomial septicemia (Acinetobacter baumanni and Pseudomonas aeruginosa bacteremia in one, P. aeruginosa bacteremia in the other). These two cases demonstrate that PCP should be included in the differential diagnosis of patients with SLE presenting with pneumonic processes. In addition, a second opportunistic pathogen should be suspected. Bronchoscopic examination should be performed if the diagnosis is not clear and should include TBLB and BAL. PMID- 11760378 TI - Inhaled nitric oxide in the management of persistent pulmonary hypertension of term infants. AB - BACKGROUND AND PURPOSE: Nitric oxide (NO) is an endogenous vasodilator that is responsible for regulating smooth muscle tone via changes in cyclic guanosine monophosphate (cGMP). Inhaled NO (iNO) causes pulmonary vasodilatation without affecting systemic vascular resistance. The aim of this study was to evaluate the efficacy and adverse effects of iNO therapy for the treatment of term infants with persistent pulmonary hypertension of the newborn (PPHN). METHODS: From June 1998 to June 2000, 26 term infants with PPHN were given iNO therapy. Another 21 term infants with PPHN who did not receive iNO therapy served as the control group. All patients had an oxygenation index (OI) of more than 25 at the beginning of the study. iNO was started at a dose of 20 ppm and weaned according to the response achieved within the 3 hours of treatment. RESULTS: The OI decreased rapidly after 30 minutes of iNO therapy and was significantly lower in the iNO group than in the control group at 30 minutes, 3, 12, and 24 hours after iNO therapy (p < 0.01). All cases in the iNO therapy group had serum methemoglobin levels of less than 2.5% and nitric dioxide (NO2) concentrations less than 2 ppm. CONCLUSIONS: We conclude that iNO therapy produces rapid improvement in oxygenation for 24 hours without short-term side-effects in term infants with PPHN. If a high dose of NO (80 ppm) is used, serum methemoglobin and NO2 values should be monitored. PMID- 11760379 TI - Ductal adenocarcinoma of the prostate with endometrioid features in a 69-year-old man. AB - We describe a case of ductal adenocarcinoma of the prostate with endometrioid characteristics presenting as painless hematuria and intraurethral tumor. A 69 year-old man had intermittent painless hematuria for 2 months. The serum prostate specific antigen concentration was elevated (22.0 ng/mL). An enlarged prostate with a necrotic tumor was noted in the right lobe of the prostate on computerized tomography and magnetic resonance imaging studies. A polypoid and worm-like tumor was found within the prostatic urethra near the verumontanum. The tumor had a distinctly papillary configuration with a focal glandular structure on microscopy. Radical prostatectomy was performed and histology of the tumor specimen revealed it to be composed of a closely packed glandular structure lined by single layers of high columnar cells with focal stratification. Frequent papillary projections of glandular epithelium and intraglandular bridging were noted, with a histopathologic appearance similar to endometrioid carcinoma of the uterus. Androgen deprivation therapy was started immediately following surgery. No evidence of recurrence or metastasis was found at follow-up 27 months postoperatively. Distinct features of ductal adenocarcinoma of the prostate include intraurethral papillary tumor close to the verumontanum, urethral obstruction, and easy bleeding of the tumor. Its more aggressive behavior than classical microacinar adenocarcinoma of the prostate makes early recognition of this type of prostatic malignancy important. PMID- 11760380 TI - Imaging findings of intradiaphragmatic bronchogenic cyst: a case report. AB - Isolated intradiaphragmatic bronchogenic cysts are extremely rare. Here, we report a case of intradiaphragmatic bronchogenic cyst with calcifications in a 34 year-old man presenting with no clinical symptoms. Imaging studies of the chest, including chest roentgenogram and computerized tomography (CT), revealed a left posterior mediastinal mass that abutted onto the left diaphragmatic crus with multiple calcifications and showed no enhancement after contrast administration on CT. The patient underwent surgical resection of the mass. Intradiaphragmatic bronchogenic cyst with calcifications was diagnosed by pathology. The patient was discharged 10 days after the operation, and no complication was found 3 months later at follow-up. PMID- 11760381 TI - Cerebral amyloid angiopathy associated with hemorrhage: immunohistochemical study of 41 biopsy cases. AB - The relationship between cerebral amyloid angiopathy and hemorrhage was investigated by an immunohistochemical study of biopsy cases to characterize the involvement of amyloid beta-protein, apolipoprotein E, and cystatin C in cerebral amyloid angiopathy associated with hemorrhage. The amyloid-laden vessels were examined in biopsy specimens from 41 surgical cases of sporadic cerebral amyloid angiopathy (36 cases with hemorrhage and 5 cases without hemorrhage), using immunohistochemical staining with antibodies against amyloid beta-protein, apolipoprotein E, cystatin C, and alpha-smooth muscle actin. The relationship between the occurrence, recurrence, and enlargement of the hemorrhage, and the semiquantitative estimation of the cerebrovascular amyloid-related protein deposition was analyzed using Fisher's exact test. Severe amyloid beta-protein (p < 0.013) and apolipoprotein E (p < 0.013) immunoreactivity were risk factors for the occurrence of the hemorrhage. Severe cystatin C immunoreactivity was a risk factor for the occurrence (p < 0.002) and enlargement (p < 0.014) of the hemorrhage, and tended to induce recurrent hemorrhage (p < 0.103). In addition, loss of the vascular smooth muscle was observed in the intensely amyloid-laden vascular walls that showed cystatin C-immunoreactivity. The present study indicates that intense amyloid beta-protein deposition with cystatin C deposition weakens the cerebrovascular walls, and that cystatin C deposition is a strong predictor of hemorrhage in cerebral amyloid angiopathy. PMID- 11760382 TI - Task-related signal decrease on functional magnetic resonance imaging. AB - An atypical pattern of signal change was identified on functional magnetic resonance (fMR) imaging in pathologic patients. Three normal volunteers and 34 patients with pathologic lesions near the primary motor cortex underwent fMR imaging with echo-planar imaging while performing a hand motor task. Signal intensities were evaluated with the z-score method, and the time course and changes of the signal intensity were calculated. Nine of the 34 patients with pathologic lesions displayed a significant task-related signal reduction in motor related areas. They also presented a conventional task-related signal increase in other motor-related areas. The time courses of the increase and decrease were the inverse of each other. There was no significant difference between rates of signal increase and decrease. Our findings suggest that this atypical signal decrease is clinically significant, and that impaired vascular reactivity and altered oxygen metabolism could contribute to the task-related signal reduction. Brain areas showing such task-related signal decrease should be preserved at surgery. PMID- 11760383 TI - Laminoplasty improves respiratory function in elderly patients with cervical spondylotic myelopathy. AB - Respiratory insufficiency after acute cervical trauma is well documented, but the relationship between respiratory function and chronic lesions, such as cervical spondylosis, has received scant attention. This clinical study investigated the effect of cervical spondylosis on respiratory function in 12 patients over 65 years of age who underwent expansive laminoplasty. Functional and neurological status were assessed using the Japanese Orthopaedic Association (JOA) scale and Neurosurgical Cervical Spine Scale (NCSS). To assess the effect of laminoplasty on respiratory function in patients with cervical spondylotic myelopathy, lung volumes including vital capacity, tidal volume (TV), inspiratory reserve volume, expiratory reserve volume, inspiratory capacity, and forced expiratory volume were measured by spirometer before surgery and 6 months after surgery. The arterial blood gas values were also measured before and after surgery. All patients showed functional improvement after surgery, and neurological examination 6 months after surgery revealed a significant improvement in both JOA scale and NCSS scores (p < 0.001). There were no significant differences in most lung volumes, but TV (p = 0.039) at 6 months after surgery showed a significant increase compared to before surgery. PCO2 also showed a significant reduction after surgery (p = 0.047). This limited study revealed that laminoplasty improved respiratory function in patients over 65 years of age with cervical spondylotic myelopathy. Lung volume measurement may be one method to estimate spinal cord function after a surgical procedure. PMID- 11760384 TI - Isolated abducens nerve paresis associated with incomplete Horner's syndrome caused by petrous apex fracture--case report and anatomical study. AB - A 17-year-old male presented with a wound on the right temporal region, oozing hemorrhagic necrotic brain tissue and cerebrospinal fluid, following a fall. Computed tomography showed temporoparietal and petrous apex fractures on the right. Neurological examination revealed abducens nerve paresis, ptosis, and myosis on the right side. The patient was treated surgically for the removal of the free bony fragments at the fracture site and to close the dural tear. The abducens nerve paresis, ptosis, and myosis persisted at the 3rd monthly postoperative follow-up examination. The anatomy of the abducens nerve at the petroclival region was studied in four cadaveric heads. Two silicone-injected heads were used for microsurgical dissections and two for histological sections. The abducens nerve has three different angulations in the petroclival region, located at the dural entrance porus, the petrous apex, and the lateral wall of the cavernous segment of the internal carotid artery. The abducens nerve had fine anastomoses with the trigeminal nerve and the periarterial sympathetic plexus. There were fibrous connections extending inside the venous space of the petroclival area. The abducens nerve seems to be vulnerable to damage in the petroclival region, either directly by trauma to its dural porus and petrous apex or indirectly by stretching of the nerve through the nervous and/or fibrous connections. Concurrent functional loss of the abducens nerve and the periarterial sympathetic plexus clinically manifested as incomplete Horner's syndrome in our patient. PMID- 11760385 TI - Spontaneous migration of a bullet in the cerebellum--case report. AB - A 15-year-old boy presented with a gunshot wound in the left cerebellar hemisphere. He was confused and left cerebellar signs were noted. The patient underwent the first surgery for debridement of the entry wound in the left parietal region and second surgery to remove the bullet. However, the bullet could not be located via a left unilateral suboccipital craniectomy in the park bench position, because it had migrated to the opposite side due to the effects of gravity in just a few hours. Skull radiography obtained just before the third surgery showed that the bullet had returned to the left side, and it was removed easily via the previous craniectomy in the sitting position. The clinical course suggests that in removing a bullet, skull radiography or computed tomography should be obtained just before surgery, or even intraoperatively, and that those findings should be the basis for the surgical procedure and operative position. PMID- 11760386 TI - Delayed central respiratory dysfunction after Wallenberg's syndrome--case report. AB - A 68-year-old man presented with Wallenberg's syndrome consisting of ataxia, dysphagia, hypesthesia on the left side of the body, and Horner's syndrome on the right. Magnetic resonance (MR) imaging revealed a right lateral medullary infarction and small multiple lacunae scattered in the upper medulla. Neurological symptoms improved in a week and the patient was discharged with mild residual hypesthesia on the left side. However, 31 days later, he was emergently admitted after suddenly becoming apneic and losing consciousness. MR imaging detected no new lesion. The patient was placed under ventilation support for 48 hours before regaining normal respiratory function. Medullary infarction sometimes causes catastrophic respiratory failure, but Wallenberg's syndrome caused by lateral medullary infarction is rarely associated with central respiratory dysfunction, and delayed onset of central respiratory dysfunction is extremely unusual. Delayed onset of central respiratory failure is a life threatening complication of the medullary infarction causing Wallenberg's syndrome, which in general is not recognized. PMID- 11760387 TI - Pathological laughter as a presenting symptom of petroclival meningioma--case report. AB - A 35-year-old male presented with symptoms of 'pathological laughter' occurring for 6 months and progressive ataxia and right facial nerve paresis for 2 months. Neuroimaging revealed a large petroclival meningioma. The tumor was well defined and only moderately vascular, and could be relatively easily resected. The symptom of pathological laughter disappeared immediately and his gait improved to normal within a week of surgery. Pathological laughter as a presenting symptom of petroclival meningioma is extremely rare. The symptom of pathological laughter may have localizing value. PMID- 11760388 TI - Spontaneous thoracic spinal cord herniation--case report. AB - A 54-year-old female presented with spontaneous thoracic spinal cord herniation manifesting as chronic progressive motor weakness in both legs. Spastic paraparesis (4/5) and pathological reflexes such as ankle clonus were noted. She also had mild bladder dysfunction but no bowel dysfunction. She had no sensory disturbance, including tactile and pinprick sense. Magnetic resonance (MR) imaging revealed that the atrophic spinal cord was displaced into the ventral extradural space at the T4-5 intervertebral level with markedly dilated dorsal subarachnoid space. Computed tomography obtained after myelography showed no evidence of intradural spinal arachnoid cyst. She underwent surgical repair of the spinal cord herniation via laminectomy, and spinal cord herniation through the ventral dural defect was confirmed. Postoperative MR imaging revealed improvement of the spinal cord herniation, but her symptoms were not improved. Spontaneous spinal cord herniation is a rare cause of chronic myelopathy, occurring in the upper and mid-thoracic levels, and the spinal cord is usually herniated into the ventral extradural space. Early differential diagnosis from intradural spinal arachnoid cysts is important for a satisfactory outcome. PMID- 11760389 TI - Spinal tanycytic ependymoma associated with neurofibromatosis type 2--case report. AB - An 18-year-old girl with a 5-year history of neurofibromatosis type 2, consisting of bilateral acoustic tumors and a meningioma at the planum sphenoidale, presented with an intramedullary mass at the T-1 level, and underwent total removal of the tumor. Histological examination showed that the tumor consisted of markedly elongated spindle-shaped cells, which were immunopositive for S-100 protein and glial fibrillary acidic protein. Ultrastructural examination showed microvilli-lined lumina and prominent intercellular junctions, which were characteristic ependymal features. These findings were compatible with the diagnosis of tanycytic ependymoma. This rare subtype of ependymoma appears to arise through inactivation of NF2, in addition to some typical ependymomas. PMID- 11760390 TI - Cryptococcal meningoencephalitis presenting with an unusual magnetic resonance imaging appearance--case report. AB - A 61-year-old female with a past history of gastric cancer presented with altered mental status, a few seizures, and low-grade fever. Lumbar puncture revealed elevated cerebrospinal fluid (CSF) pressure, lymphocytic pleocytosis, elevated protein level, remarkably decreased glucose level, and presence of cryptococcal antigen. Cryptococcus neoformans was identified by India ink staining and culture of CSF. The patient was given antifungal agents intravenously and intrathecally. CSF findings improved and C. neoformans could not be detected in CSF one month after the onset. Cerebral sulcal hyperintensity was identified in the bilateral frontal and parietal lobes on fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging one month after the onset, but no leptomeningeal enhancement was detected in the affected sulci on T1-weighted MR imaging. The sulcal hyperintensity on FLAIR imaging developed in the bilateral temporal and occipital lobes 2 months after the onset. CSF findings obtained by lumbar puncture were within the normal range except for pressure. However, neurological deterioration and reconfirmation of C. neoformans in CSF indicated recurrent cryptococcal inflammation. The sulcal hyperintensity on FLAIR imaging may indicate a high CSF protein concentration in the subarachnoid space. Such cerebral sulcal hyperintensity is an unusual MR imaging finding of cryptococcal meningoencephalitis, and may be an early sign of procrastinating process or recurrent inflammation even if the findings of CSF obtained by lumbar puncture are normal. PMID- 11760391 TI - Enigmas in familial Mediterranean fever (FMF). PMID- 11760392 TI - The other physician behind the use of colchicine for the treatment of familial Mediterranean fever. PMID- 11760393 TI - Neutrophil activation in Behcet's disease. AB - OBJECTIVE: Neutrophils are implicated in the pathogenesis of Behcet's disease (BD). Various functions of neutrophils are studied to clarify this role. METHODS: The oxidative burst and phagocytic functions of neutrophils and surface molecules associated with neutrophil activation (CD10, CD14 and CD16) were investigated in BD patients by flow cytometric methods. Patients with inflammatory arthropathies, sepsis and healthy controls were also studied. RESULTS: In the oxidative burst experiments, after fMLP and PMA stimulation, stimulation index was found to be significantly decreased in patients both with BD and sepsis compared to healthy controls and inflammatory arthropathies (p < 0.001 and p < 0.01, respectively). The phagocytosis of labelled E. coli particles in patients with BD was not different from that of the healthy controls, while it was decreased in diseased controls (p < 0.001). The surface density of neutral endopeptidase (CD10) and the mean percentage of LPS receptor (CD14) was found to be significantly higher in both BD patients and diseased controls (p < 0.001). The mean percentage of CD16 expression was only low in patients with sepsis (p < 0.001), whereas CD16 intensity on cells was found to be lower in patients with BD as well as in sepsis (p < 0.01). CONCLUSION: These findings indicate the presence of in vivo pre activated neutrophils in BD. A similar activation was also a feature of severe inflammatory disorders. PMID- 11760394 TI - Interactions of nitric oxide and superoxide dismutase in Behcet's disease. AB - OBJECTIVE: Nitric oxide (NO) is produced in increased amounts in inflammatory conditions and may cause tissue injury by reacting with superoxide to yield peroxynitrite, a powerful toxin. Superoxide dismutase (SOD) scavenges superoxide and inhibits the formation of peroxynitrite, thereby suppressing the resulting injury and regulating the bioavailability of NO. We conducted a study to assess serum NO and SOD in patients with Behcet's disease (BD) and correlate their levels with disease activity. METHODS: Serum NO concentrations and SOD activities were determined in 25 BD patients (mean age: 36 years; male/female: 13/12) and in 15 healthy controls. BD patients were allocated into two groups according to disease activity (active/inactive: 11/14). RESULTS: In patients with active disease, NO levels were found to be significantly elevated, while SOD activities were comparable to the control group. Conversely, patients with inactive disease exhibited markedly high SOD activities and normal NO levels. Moreover, there was a positive correlation between SOD activity and NO levels in patients with inactive BD (r = 0.562, p < 0.05). CONCLUSION: We propose that NO-associated injury of tissues, particularly the endothelium, may be important in the etiopathogenesis of vasculitis in BD, and SOD may play a protective role against inflammation. PMID- 11760395 TI - HLA-B51 and its allelic types in association with Behcet's disease and recurrent aphthous stomatitis in Korea. AB - OBJECTIVE: This case-control study was undertaken to evaluate the association of HLA-B51 antigen and its allelic types with Behcet's disease (BD) and with recurrent aphthous stomatitis (RAS), to investigate the degree of this association with diagnostic types and clinical variables of BD. METHODS: The DNA typing of HLA-B51 by nested PCR-SSP was performed in 61 patients with BD, 56 patients with RAS, and in 70 healthy controls. Also, blind quality control study was done to assess the accuracy of nested PCR-SSP in HLA-B51-positive and negative BD patients on the microlymphocytotoxicity. In addition, direct DNA sequencing analysis was carried out in HLA-B51-positive individuals. RESULTS: The outcome of nested PCR-SSP showed 100% concordance with those of the microlymphocytotoxicity. The prevalence of HLA-B51 in patients with BD was 55.7%, 16.1% in patients with RAS, and 15.7% in healthy controls. According to the diagnostic types of BD, all ten patients with complete BD had HLA-B51 antigen, and 47.1% in patients with incomplete BD (p = 0.002). In addition, the prevalence of HLA-B51 was statistically significant in patients with BD who had uveitis (p = 0.003) or erythema nodosum (p = 0.042). Direct DNA sequencing analysis revealed that the major allelic types in BD, RAS, and in healthy control were mostly HLA B*51011. CONCLUSIONS: Compared to patients with RAS or healthy controls, prevalence of HLA-B51 in the Korean patients with BD was much higher. The BD patients with B51 seemed to be susceptible for manifesting uveitis, erythema nodosum, and the full-blown syndrome as complete BD. Therefore the presence of HLA-B51 antigen in BD patients would be a genetic marker for the severe disease. In addition, there was no difference on the major allelic types of HLA-B51 in BD, RAS, and in healthy control. PMID- 11760396 TI - Synovial fluid cytokine levels in Behcet's disease. AB - OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behcet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL 1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL 1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process. PMID- 11760397 TI - Nailfold capillary abnormalities in patients with familial Mediterranean fever. AB - OBJECTIVE: To determine the frequency and the degree of the nailfold capillary abnormalities in patients with familial Mediterranean fever (FMF). METHODS: We studied 67 (M/F: 28/39) patients with FMF. Thirty-seven healthy subjects (16/21), 19 patients (0/19) with systemic lupus erythematosus (SLE), and 8 patients (0/8) with scleroderma (PSS) were also studied. All participants were questioned for the presence of Raynaud's phenomenon (RP). Capillary loops of eight fingers were evaluated and scored with respect to avascular areas, tortuosity, enlargement and extravasations by the conventional capillary microscopy. Both FMF patients and healthy controls were examined in a blind manner. RESULTS: FMF patients differed from healthy controls by the presence of increased tortuosity and enlargement of capillary loops, but not by microhemorrhages. Being female and the presence of RP were the factors that correlated with the capillaroscopic findings. CONCLUSION: Capillary abnormalities are seen in patients with FMF. PMID- 11760398 TI - A reassessment of the International Study Group criteria for the diagnosis (classification) of Behcet's syndrome. AB - OBJECTIVE: Patients with ulcerative colitis (UC) and Crohn's disease (CD) were not represented in the diseased controls group that had been utilised in the development of the International Study Group (ISG) criteria for the diagnosis of Behcet's syndrome (BS). Having similar features, both of these conditions can pose problems in the differential diagnosis of BS. Moreover, there has been a recent awareness of coexistence of BS and familial Mediterranean fever (FMF). The aim of this study was to reassess the performance of ISG criteria among patients with BS and other rheumatological conditions, specifically including those with CD, UC, and FMF. METHODS: 302 consecutive patients with BS and 438 patients with other rheumatological conditions were surveyed for the presence or absence of the features of BS by means of a standard form which had been prepared according to ISG criteria. All control patients with a history of oral ulcer had a pathergy test and an eye examination by an experienced ophthalmologist with a slit lamp. The sensitivity and specificity of the ISG criteria were calculated. RESULTS: Seven of 302 patients with BS (2%) did not fulfill the ISG criteria while 5 of 438 controls (1%) fulfilled the ISG criteria. CONCLUSION: In this study ISG criteria performed well in correctly classifying BS. Further specificity studies might be considered in CD. PMID- 11760399 TI - Deep vein thrombosis in Behcet's disease. AB - OBJECTIVE: We aimed to describe the epidemiological and clinical aspects of deep vein thrombosis (DVT) in Behcet's disease (BD) and to determine the patients at high risk for this complication. METHODS: Among 113 patients with BD according to the international criteria for classification of BD, those with DVT were retrospectively studied. The diagnosis of DVT was made in all cases using conventional venous angiography, venous ultrasonography and/or thoracic or abdominal computed tomography. Patients were divided in two subgroups according to the occurrence of DVT other than cerebral thromboses. The medical records of these patients were reviewed in order to investigate their past medical history and evaluate their response to the treatment prescribed. Clinical and genetic factors (HLA B51 and MICA 6) that might contribute to DVT were analysed by comparing patients with and without DVT. Results of our series were compared to those of other series in the literature. Statistical analysis was by Chi square with necessary correction and Fischer tests. RESULTS: Forty-four patients (38.9%) had deep vein thrombosis of various systems with 81 localisations. There were 40 men and four women (mean age 28.1 years; range 17-60). DVT appeared after the onset of disease with a mean delay of 3.8 years. In 6 cases, DVT revealed BD. When we evaluated the risk of DVT coexistence with other clinical findings and genetic factors (HLA B51 and MICA 6), we found a significant positive correlation with sex, and positive pathergy test. CONCLUSION: In our series, occurrence of DVT was significantly associated with male gender and positive pathergy test. PMID- 11760400 TI - Osteonecrosis and bone infarction in association with Behcet's disease: report of two cases. AB - We describe two cases with Behcet's disease (BD) developing osteonecrosis or bone infarction. One patient developed the extensive bone infarction of the left knee without the use of corticosteroids. The other patient had osteonecrosis at the right femoral head. He had had a past history of significant corticosteroid administration to treat several complications of BD such as central nervous system involvement, uveitis, gastrointestinal involvement, and pulmonary involvement. Anticardiolipin (aCL) antibodies were positive in these two patients. One was IgG type, and the other was IgM type. However, it remains unclear that there is relationship between the presence of aCL antibodies and occurrence of osteonecrosis. PMID- 11760401 TI - Renal involvement in Adamantiades-Behcet's disease. Case report and review of the literature. AB - A patient with Adamantiades-Behcet's disease with renal involvement is reported. This patient fulfilled the International Study Group criteria for the disease. Kidney biopsy was performed and proliferative glomerulonephritis with deposition of IgA and IgM immunoglobulins were demonstrated. Review of the literature demonstrates that renal involvement in this disease is not so rare as it was believed. Crescent formation and IgA nephropathy are infrequently observed. Treatment of renal involvement may require immunosuppressive drugs. PMID- 11760402 TI - Behcet's disease complicated by pylephlebitis and hepatic abscesses. AB - A 22 year old man presented with fever, abdominal pain, weight loss and diarrhea. Past medical history revealed recurrent aseptic meningitis, uveitis, and erythema nodosum. Further inquiry unveiled a prominent history of oral aphthous ulcers; all features of Behcet's disease. Imaging revealed mesenteric arteritis and pylephlebitis, septic thrombophlebitis of the portal vein, a previously unrecognized complication of Behcet's disease, with multiple intrahepatic abscesses. Portal venography demonstrated an extensively diseased, expanded, and obstructed portal venous system. Blood cultures and portal vein aspirate yielded polymicrobial flora. Percutaneous intraportal thrombolytic therapy and mechanical thrombectomy were attempted to restore flow to the portal venous system. This distinctly rare manifestation of Behcet's Disease, pylephlebitis, may result from ischemic injury and structural compromise of the bowel mucosa, resulting from underlying vasculitis. PMID- 11760403 TI - Behcet's disease: an update on the pathogenesis. AB - Behcet's disease is a chronic inflammatory disorder of unknown etiology. It has long been postulated that immunological abnormalities, which are possibly induced by microbial pathogens in genetically susceptible individuals, are important in its pathogenesis. Recent findings have both supported the significance of genetic factors and better defined the nature of inflammation in Behcet's disease. Molecular genetic studies have strengthened the primary association of HLA-B51 with Behcet's disease. The exact pathogenic mechanism of the HLA-B51 molecule is still unknown, and its contribution to the overall genetic susceptibility to Behcet's disease is estimated to be less than 20%. Spontaneous and/or induced overexpression of pro-inflammatory cytokines (mainly Th1 type) from various cellular sources seems responsible for the enhanced inflammatory reaction in Behcet's disease, and it may be associated with the genetic susceptibility. An antigen-driven immune response superimposed on this primed-state and induced by heat shock proteins or other peptides from different strains of streptoccocci or other microbial agents has been suggested to trigger manifestations of Behcet's disease. Endothelial activation/injury and the resultant occlusive vasculopathy may also contribute to the tissue damage. PMID- 11760404 TI - Familial Mediterranean fever (FMF)-associated amyloidosis in childhood. Clinical features, course and outcome. AB - OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disorder of childhood characterized by attacks of fever and serositis. Renal amyloidosis is the most important complication of the disease that determines the prognosis. METHODS: Forty-eight Turkish FMF patients with amyloidosis who have been followed at the two hospitals in Ankara were included in this study. RESULTS: All patients with amyloidosis had been symptomatic for FMF at the time of the diagnosis (Phenotype I), none had received regular colchicine therapy and all presented with proteinuria. Ten of them had asymptomatic proteinuria; 38 had nephrotic syndrome and 8 of them had renal insufficiency (CRI) as well, at the time of the diagnosis. Regular colchicine therapy was commenced to all of the patients. At the end of observation period of 4.5 +/- 2.23 years (range 2-12 yrs) on treatment, nephrotic syndrome resolved in 13 patients and proteinuria was lost in 5 of them. None but 2 of the patients who were diagnosed at proteinuric stage progressed to end stage renal failure (ESRF). Seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) were systematically investigated in 32 patients. Six of the seven studied mutations were found in these patients and clinical diagnosis was confirmed by mutation analysis in 24 patients. Eight patients were found to have mutations on one of the alleles. CONCLUSION: Amyloidosis is the most serious complication of FMF. Colchicine treatment ameliorates the progression of renal disease in the patients who presented with proteinuria and even with nephrotic syndrome. No correlation between the outcome of the patients with nephrotic syndrome and the degree of proteinuria and/or serum albumin levels at the initiation of treatment were noted. Progression to ESRF seems inevitable despite colchicine therapy after the development of CRI in patients with FMF associated amyloidosis. PMID- 11760405 TI - Increased neutrophil apoptosis during attacks of familial Mediterranean fever. AB - AIM: Apoptosis is a programmed form of cell death. Recently much attention has been devoted to the role of apoptosis in rheumatological diseases. We have aimed to analyze apoptosis in the inflammatory pathway of familial Mediterranean fever (FMF). METHODS: 26 FMF patients and 12 age and sex matched controls were the subject of the study. Twelve of the patients were analyzed during an FMF attack whereas samples were obtained at least a week after an attack in 14. Four of the patients had renal amyloidosis. Whole blood was treated with ammonium chloride for RBC lysis. Subsequently the cells were stained with propidium iodide and annexin. Neutrophils and lymphocytes were gated separately for analysis by flow cytometry. We have also analyzed cellular Fas and Fas-ligand expression in these cells. RESULTS: The mean age of the patients was 12.00 +/- 3.17, and was not different than the control subjects. Erythrocyte sedimentation rate and CRP levels were significantly elevated in the attack group as compared to the attack free group. The mean levels of neutrophil apoptosis in the FMF patients with an attack, attack-free and controls were 12.94 +/- 11.78, 6.60 +/- 7.83 and 3.98 +/- 4.27, respectively. Lymphocyte apoptosis in the same groups were 7.84 +/- 8.63, 2.75 +/- 2.33, and 1.22 +/- 0.93, respectively. Neutrophil and monocyte apoptosis was significantly increased during the attack as compared to the controls (p < 0.05). However lymphocyte apoptosis was not different between the aforementioned groups. On the other hand, lymphocyte apoptosis was significantly increased in the SLE patients (p < 0.05), whereas neutrophil apoptosis was not. Fas staining of neutrophils were not different between the groups (p > 0.05). On the other hand the difference between the groups for FasL was significant (p < 0.05). CONCLUSION: Neutrophil and monocyte but not lymphocyte apoptosis was significantly increased during FMF attacks reminding us that FMF is an autoinflammation of certain peripheral cells. The increased apoptosis in these patients maybe regarded as a response to clear the unwanted inflammatory cells. On the other hand the increased apoptosis maybe the explanation of the self limited nature of the FMF attacks. Future studies will enlighten us on the significance of this increased apoptosis in the process of inflammation. PMID- 11760406 TI - Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment. AB - OBJECTIVE: To evaluate growth process and insulin like growth factor-1 (IGF-1) levels in children with familial Mediterranean fever (FMF). METHODS: This prospective study group consisted of 51 children with FMF under colchicine therapy (20 boys, 31 girls) and 42 healthy children (22 boys, 20 girls). All children were prepubertal. Bone ages and IGF-1 levels were determined in all cases. Height velocity (HV), height standard deviation score (SDS), target height and target height SDS were calculated. RESULTS: There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and diseased subjects. HV of children with FMF did not differ significantly from the control group. There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and FMF subjects. HV of children with FMF did not differ significantly from the control group. There was no significant correlation between disease duration, number of attacks, erythrocyte sedimentation rate and HV, HSDS and IGF-1 levels of FMF patients. There was positive correlation between cumulative colchicine dose and HV (r = 0.29). CONCLUSION: Growth and IGF-1 levels of children with FMF do not differ from their healthy peers. However, there was positive correlation between HV and cumulative colchicine dose. This study suggests that colchicine not only has no adverse influence on growth, but more by suppressing disease activity and inflammation it has an enhancing role. PMID- 11760407 TI - Colchicine treatment in familial Mediterranean fever: an indirect effect on in vitro serum amyloid A secretion via leukocyte derived factors. PMID- 11760408 TI - The therapeutic effect of cigarette smoking on oral/genital aphthosis and other manifestations of Behcet's disease. PMID- 11760409 TI - A case of familial Mediterranean fever, Behcet's disease and polyarteritis nodosa complicated by perirenal haematoma. PMID- 11760410 TI - Reporting a desensitization protocol for colchicine treatment. PMID- 11760411 TI - Multiple venous thrombosis in a patient with Behcet's disease and protein C deficiency. PMID- 11760412 TI - Bilateral uveitis in a 7-year-old patient with familial Mediterranean fever. An extremely rare complication. PMID- 11760413 TI - Sexually transmitted diseases among Italian heterosexuals: results from a general population survey within a European Concerted Action. PMID- 11760414 TI - [Type I diabetes in Lazio. Note 1: incidence in 1989-1998]. PMID- 11760416 TI - [Food: a significant source of exposure to aromatic polycyclic hydrocarbons]. PMID- 11760415 TI - [Determinants of milk consumption among compulsory education students in southern Sardinia]. PMID- 11760417 TI - [Trace elements in red and white wines from various Italian regions]. PMID- 11760418 TI - [Eating behavior of children and parents and patterns of hygienic safety: study of elementary schools in Campobasso]. PMID- 11760420 TI - [Evaluation of the applicability of a questionnaire on occupational health risks in agriculture]. PMID- 11760419 TI - [Health in developing countries: evaluation of nursing care at a provincial hospital in the Republic of Guinea]. PMID- 11760421 TI - [Risk perception among residents in a region with high environmental risk]. PMID- 11760422 TI - [Role of health education in the promotion of vaccination in school-age children: parents' responsibility]. PMID- 11760424 TI - [Towards a single vaccine]. PMID- 11760423 TI - [Responsibility of general practitioners and pediatricians in the free choice of vaccination in childhood]. PMID- 11760425 TI - [Principles of and criteria for certification of preventive services]. PMID- 11760426 TI - [Pneumococcal vaccine in the Puglia region]. PMID- 11760427 TI - [Peer accreditation handbook for health education functions and structure in local health units and regional health administration]. PMID- 11760428 TI - [Accreditation handbook on vaccination services]. PMID- 11760430 TI - [Accreditation of health districts: an overview of regional models]. PMID- 11760429 TI - [Accreditation of prevention departments: experience of the Local Health Unit of Bologna city]. PMID- 11760431 TI - [Pneumococcal vaccine in the Basilicata region]. PMID- 11760432 TI - [Pneumococcal vaccine: experience in the Abruzzo region]. PMID- 11760433 TI - [Pneumococcal vaccine. Methodological experience in general medicine]. PMID- 11760434 TI - [Epidemiology and clinical course of S. pneumoniae infections in children]. PMID- 11760435 TI - [Conjugated pneumococcal vaccine: a clinical profile]. PMID- 11760436 TI - [Pneumococcal vaccine of the new national health plan]. PMID- 11760437 TI - [Pneumococcal vaccine]. PMID- 11760438 TI - [Institutional and normative features of the university-territory relationship]. PMID- 11760439 TI - [Organizational problems and expectations of health care workers degrees]. PMID- 11760440 TI - [Significance of health degree classes in prevention]. PMID- 11760441 TI - [Significance of post-graduate degrees]. PMID- 11760442 TI - [Prospects for medical specialization schools]. PMID- 11760443 TI - [Perceptions, communication, and management of risk in vaccination]. PMID- 11760444 TI - [The genesis of medical waste]. PMID- 11760445 TI - [Classification and management of medical waste]. PMID- 11760446 TI - [Management of radioactive waste resulting from biomedical activities]. PMID- 11760447 TI - [Medical waste: evolution of the problem]. PMID- 11760448 TI - [The correct selection and salvage of medical waste in health facilities]. PMID- 11760449 TI - [Penal responsibility for the management of medical waste in public or private facilities. The role of health administrators after the adoption of regulation n. 219/2000]. PMID- 11760450 TI - [Risk for health personnel]. PMID- 11760451 TI - [Practical guidelines on the management of medical waste]. PMID- 11760452 TI - [Functional neuroimaging in movement disorders]. AB - Positron Emission Tomography (PET) and Single Photon Emission. Computed Tomography (SPECT) highly contribute to the management of patients with movement disorders by measuring regional cerebral metabolism/blood flow and dopamine receptors. Imaging of the dopaminergic system is a powerful tool for distinguishing patients with neurodegenerative disorders, such as Parkinson's disease. Parkinsonism is most of the time caused by idiopathic Parkinson's disease. Considering the differences in therapeutic response and prognosis, differentiation between Parkinson's disease and "parkinsonism-plus syndromes" is important. Visualisation of pre- and post-synaptic D2 dopamine receptors by using receptor ligands helps to discriminate between Parkinson's disease and "parkinsonism-plus syndromes" as Parkinson's disease is a presynaptic disease. Early disease detection in subjects suspected at risk for developing Parkinson's disease has become possible using ligands for the dopamine transporter. Functional imaging modalities are useful in the management of patients with movement disorders, are able to monitor in an objective way the efficacy of new pharmacological therapies, can document the effect of neuronal grafting for Parkinson's disease, and delineate the progression of these diseases. PMID- 11760453 TI - [Gastrointestinal immunology]. AB - The paper is devoted to the actual questions of gastrointestinal immunology. In the first part, structure and function of gut-associated mucosal tissue (GALT), including the role of secretory immunoglobulins and importance of oral tolerance are shown. In the second part, the pathogenesis of unknown origin gastrointestinal and liver diseases (gluten sensitive enteropathy, inflammatory bowel diseases, autoimmune liver diseases, autoimmune pancreatitis) is described. Then the immunology of some gastrointestinal infections (Helicobacter pylori, hepatitis virus B and C, and HIV) and of alcoholic and drug induced, liver diseases is briefly summarized. PMID- 11760454 TI - [The role of autopsy in verifying diagnostic accuracy at the intensive care unit]. AB - The accuracy of the clinical diagnoses compared to the findings of an autopsy is a more relevant characteristic of the quality of care than the length of stay in the hospital or the daily costs of the stay. The aim of this retrospective study was: a) to compare the clinical and pathological diagnoses, b) to determine the amount of new information supplied by the autopsy and c) to determine wether the knowledge of correct clinical diagnosis would have resulted in a change of therapy. At the medical ICU 163 patients died during 1998, autopsy was performed in 110 cases. Agreement of clinical and pathological diagnoses and causes of death were retrospectively assessed by a board. Acute myocardial infarction accounted for 26% of deaths, pneumonia and respiratory insufficiency for 15%, cardiac failure for 14%, sepsis for 14%, stroke for 13%, pulmonary embolism for 5% and others for 13%. The accuracy of the clinical cause of death was proved in 81% of the cases. The main disease was diagnosed correctly in 86% of the cases. As a tool in quality control, the agreement of clinical and pathological diagnoses and causes of death proved to be good during the examined period of time. PMID- 11760455 TI - [Biological effects of microorganisms, their substances and immunosuppressive agents in mice]. AB - The author provide evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defence. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating affect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora. With ageing, effect of immunomodulants can change and become indifferent or even suppressive. Dose dependence of stimulating or suppressing effect of immunomodulants may be related to their non-immunological effects (endotoxin effect, bacterial translocation). Finally, on the basis of the results, the authors consider the germfree mouse suitable for examining the effect of a given agent in the practice, on one hand, and for observing the host organism's reactions, free from the influence of the normal microbial flora, on the other. Along with the known physiological and pathological events, the results draw also attention to as distant fields as drug sensitivity, drug interactions influencing drug sensitivity. The author put emphasis on importance of germfree environment during immunosuppressive treatments in humans and when making special examinations under experimental conditions. PMID- 11760456 TI - [Acute lymphoblastic leukemia in a patient with congenital hemolytic anemia: case report]. AB - The authors present a case of a 13-year-old girl with a history of congenital hemolytic anemia (spherocytosis) who developed acute lymphoblastic leukaemia. She received treatment according to the ALL-BFM 91 protocol standard risk group. During maintenance therapy an aplastic crisis caused by Parvovirus B 19 infection had developed. Chemotherapy was stopped in September 1999, and the patient remained in complete remission. In January, 2000 the patient presented with jaundice, caused by a stone in the ductus choledochus. Cholecystectomy and splenectomy were performed, and the the girl became symptomfree. The authors review the most frequent complications of congenital hemolytic anemias (aplastic crisis, haemolytic crisis and cholelithiasis). The occurrence of acute lymphoblastic leukaemia in a patient with congenital hemolytic anemia has not been previously reported. PMID- 11760457 TI - [Development, attachment and relationship: new psychoanalytical concepts]. AB - Authors present the evolution of psychoanalytical views of how a child perceives and contruct the world. They begin with Freud's thought and go through works of Klein, Spitz, Mahler, Bowlby, ending with modern thought of Stern. Developments in understanding of the infant by observations taken through the last thirty years are outlined and implications for psychoanalytical theory and treatment of mental problems are described. PMID- 11760458 TI - [Hypochondriasis: mechanisms of a disorder in the light of psychoanalytical concepts]. AB - This paper presents the mechanisms of hypochondria from the perspective of different theoretical orientations in psychoanalysis. The authors analyze the significance of narcissism, the death instinct (mainly from the perspective of Melanie Klein's school) and the masochistic tendencies, in hypochondria. The paper presents the views of various psychoanalytical authors on the links between hypochondria and other mental disorders. The authors also present the theory and empirical data, showing the connection between somatoform disorders and the traumatic experiences in childhood. The authors stress the importance of the contribution of different theoretical schools in psychoanalysis to the understanding of the intra psychic work of hypochondria. PMID- 11760459 TI - [Psychophysiological correlates of primary insomnia]. AB - Psychophysiological differences between 16 patients with primary insomnia, 7 men and 9 women, of mean age 40.8 years, and 16 controls, matched according to age, sex and education, were studied. Insomniacs differed from controls in the following results: their motor activity level was higher during night, sleep efficiency was lower and complexity in slow wave sleep was higher. The Hyperarousal Scale score was higher in insomniacs and it correlated with severity of insomnia in Athens Insomnia Scale. Sleep latency in MSLT was not shorter in patients group. Reaction time was shorter, moreover, the number of presentations necessary to memorize all items of Selective Reminding Test was greater in these patients. Degree of the learning disturbance correlated with the Athens Insomnia Scale score. No correlations were found between Selective Reminding Test and standard polysomnographic parameters. To sum up, the hypothesis on 24-hour hyperarousal in primary insomnia has been confirmed and learning impairment has been documented in the present study, independent of standard polysomnographic parameters. PMID- 11760460 TI - [MSLT: an objective method of assessment of excessive sleepiness]. AB - Excessive daytime sleepiness is a serious medical problem. It appears against patient will, when he performs normal day activities. It significantly disturbes daily functioning and may be a cause of a serious accidents. Approximately 5% of the general population suffers from excessive daytime sleepiness. The most common cause of daytime sleepiness is sleep deprivation. It is also a symptom of many disorders and may be an effect of taking many drugs, especially sedative ones. Investigation continued in the seventies by W. Dement and M. Carscadon resulted in preparation of MSLT which became the most widely used, objective method of the assessment of excessive sleepiness. It has been quickly used in diagnosis of narcolepsy, obstructive sleep apnea, idiopathic hypersomnia, periodic limb movements, circadian rhythms disorders, insomnia investigations, clinical assessment of many drugs. However equipment requirements are not that complicated, but investigator knowledge and experience are the limitations of the method. We described the protocol of the test including EEG procedures, patient preparation, interpretation of the results and normal values. Indications for MSLT in the diagnosis of sleep disorders were outlined with the special emphasis on narcolepsy. PMID- 11760461 TI - [Usefulness of an original questionnaire for the sleep pattern analysis in distinguishing between some psychopathological syndromes]. AB - By the use of an original questionnaire constructed by the authors, sleep patterns in 194 patients with mental disorders admitted to the hospital were investigated. Six main psychopathological syndromes were diagnosed in this group. The results suggest that most of these syndromes exhibit their characteristic sleep patterns. Our questionnaire seems to be a simple and reliable tool helpful in comparing psychopathological syndromes between them. PMID- 11760463 TI - [Some aspects of measurement by Wechsler Intelligence Scale in the context of mental retardation diagnosis in adults]. AB - The paper deals with the problem of diagnosing mental retardation in adults, with a focus on the numerical indicator of intellectual level (intelligence quotient). According to the present standards, the process of diagnosing mental retardation demands a comprehensive approach: an evaluation of both the intellectual level and social competence, and should be carried out by a team of experts (medical consultants, a psychologist, an educationist, etc.). The paper shows that, in the process of diagnosing, excessive attention should not be paid to the indicator of intellectual level, expressed by the intelligence quotient. According to the theory of psychological testing, this indicator is saddled with some error. Its use as the main criterion in diagnosing can lead to drawing false conclusions. The paper presents the Wechsler Adults Intelligence Scale WAIS-R(PL), which is the most common tool used by Polish psychologists in diagnosing the intellectual level. It also indicates the limitations and strong points of this test in the process of diagnosing mental retardation. The article is mainly addressed to medical doctors, as it contains information relating to the problem of measurement by tests, which is scantily dealt with during the medical studies. PMID- 11760462 TI - [Bizon's method of social network and social support assessment: description of the method and its application]. AB - The development of the social network and social support assessment method designed by Bizon is concisely outlined. The final version of the measurement method is described and all its components are presented in the appendix. It consists of the Interview Questionnaire, including Social Support Inventory, the Map of Social Network, the List of Social Network, Table of the data coding and Questionnaire of Demographic Data. The main studies with this instrument are reviewed. They indicate that Bizon's method is a helpful diagnostic tool and has some advantages in comparison with similar methods applied in the studies of social support. PMID- 11760464 TI - [Mild cognitive impairment]. AB - Mild Cognitive Impairment (MCI) is a clinical syndrome (with well-established diagnostic criteria) that carries a high risk of the patient developing dementia, which means that it requires early detection, diagnosis and treatment to alleviate suffering and to attempt to reduce the resulting the burden. PMID- 11760465 TI - [Cognitive deficits in the bipolar affective disorder]. AB - Cognitive deficits have been viewed as being characteristic features of schizophrenia. Neuropsychological impairment has been also identified in depression and mania. Recent studies have suggested that patients with bipolar disorder do not make full recovery between episodes of illness and that neuropsychological dysfunction may persist beyond these episodes. Remitted bipolar patients performed worse on Wisconsin Card Sorting Test, Verbal fluency and Stroop Test than healthy controls, the results of the patients with affective disorders with psychotic features were comparable with those of schizophrenics. Some studies suggest an association between the course of illness and the intensity of cognitive deficits, this link was not confirmed in other reports. Imaging studies have shown the presence of white matter lesions and other abnormalities in the brains of bipolar patients. The relative reduction in cerebral tissue may contribute to neuropsychological impairment in subgroup of bipolar patients. Results of studies on the role of white matter lesions are inconsistent. Recent studies point to an association between decreased prefrontal cortex volume and cognitive disturbances. Attention is focused on hippocampus volume as well, since it is associated with cognitive deficits in bipolar disorder. Further studies are needed to elucidate whether a severe course of illness is associated with more pronounced cognitive disorders and whether presence of psychotic symptoms during the acute phase of the illness is a predictor of the occurrence of cognitive deficits in patients with bipolar affective disorder. PMID- 11760466 TI - [Psychiatry throughout ages: rethinking anorexia nervosa as a viable behavior in a specific sociocultural context?]. AB - Anorexia nervosa when described from a critical, historical perspective, may be successfully construed as a viable psychiatric illness. Just as fasting girls and victorian anorexics gained attention and respect in their families and communities, modern adolescent anorexics often derive reinforcement from peers and community acceptance of their self-starvation. This theoretical construction makes it possible to explain the changing nature of anorexia nervosa trough the ages and its' continued increase as well. PMID- 11760467 TI - [Disseminated intravascular coagulation(DIC)]. AB - Disseminated intravascular coagulation (DIC) remains a multifaced syndrome, which may develop with different background and aetiology into venous thromboembolism (mainly chronic, paraneoplastic DIC) or into severe bleeding, factor consumption, thrombocytopenia (i.e. gynaecological acute DIC) or may appear as microthrombotic organ hypoperfusion, organ-failure and necrosis (septic DIC variant). The understanding and consideration of pathogenetic events promotes better identification and interpretation of DIC syndrome and its categories, render more adequate diagnostics and therapy available. The vast majority of new data accumulated in the septic type of DIC, and this general review also tries to put the major emphasis on sepsis-DIC link, laboratory diagnosis and apparent new therapeutic approaches. PMID- 11760468 TI - [Dual-energy x-ray absorptiometry and quantitative ultrasound bone density examinations in primary hyperparathyroidism]. AB - The aim of this study was the analysis and comparison of bone density data obtained by dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) and the follow up of bone density after parathyroidectomy of our patients with primary hyperparathyroidism. The authors performed bone mineral density (BMD) measurements using DEXA (Hologic QDR 4500 C) and QUS (Lunar Achilles Plus) devices in 22 patients with primary hyperparathyroidism between 1997 and 1999 (19 sporadic, 1 MEN 1., 2 MEN II.). Fifteen patients underwent parathyroidectomy (13 adenoma, 2 carcinoma). According to DEXA measurements all patients had osteoporosis. The lowest bone mineral density was detected at the wrist: the mean t-score was -4.00 +/- 1.79. After parathyroidectomy nine patients were followed for a mean of 12.8 months. After one year following surgery the most significant increase in BMD was 14.6%. The QUS values did not correlate with the DEXA data before the operation and no significant changes in stiffness were detected after surgery. The QUS values do not reflect the severity of the BMD decrease by DEXA in patients with primary hyperparathyroidism. PMID- 11760469 TI - [HLA genomic tissue typing in myasthenic patients with rheumatoid arthritis]. AB - In a 36 years old male and a 56 years old female myasthenic patient thymectomy was performed several years ago. In the male patient 5, and in the female patient 7 years after the operation rheumatoid arthritis developed. The rheumatoid arthritis in the male patient was seropositive with marginal erosions in the carpometacarpal and in the tarsometatarsal joints. The female patient had no joint destruction and was seronegative as well. The female patient had also an abnormal ratio between the separated CD4 and CD8 T-cells. The major histocompatibility complex determined by the serological methods revealed a haplotype of HLA-A1-B8-D3-DQ2, which is typically due to the myasthenic disease. In the female patient the molecular analysis of the HLA-D region showed a HLA DRB1* 0401 allele, which is frequently associated with rheumatoid arthritis. The male patient had no allelic variant which could be related to his chronic disabilitating joint disease. PMID- 11760470 TI - [Postoperative depression after open heart surgery]. AB - Rehabilitation of the patients following open heart surgery is strongly influenced by the psychological conditions. Depression plays a crucial negative role in this process. Depression score was measured in patients taking part in the rehabilitation course of our institute last year (1998), 6 weeks after discharge from the hospital. Unfortunately preoperative score was not done. Beck Depression Inventory (BI) test was used. Following factors were investigated: age, gender, cross clamp and bypass time, type of anaesthesia (propofol, isoflurane or midazolam, all combined with fentanyl), ICU stay, hospital stay, hypotension, cardioversion during hospital stay and neurological disorders. Statistical analyses were performed with forward stepwise regression and ANOVA tests. 74 patients were investigated. BI score under 10 points is considered to be normal. Depression scores were significantly affected by the gender (females: r: 0.85, p = 0.005), and the ICU stay (r: 0.76, p = 0.007). Type of anaesthesia, age, hospital stay, and neurological disorders did not affected the depression score. Our results indicate, that females and patients with longer ICU stay require special attention during the perioperative period in psychological respect. PMID- 11760471 TI - [Myocarditis simulating myocardial infarction]. AB - Acute myocarditis caused by infectious mononucleosis simulated myocardial infarction, initially the quantitative and qualitative blood picture was normal. Repeated blood and serological studies confirmed the diagnosis, which was altered by acute porphyria caused by infection. In each case of young patients with myocardial infarction and in older patient with coexisting infectious symptoms, myocarditis must be considered. Since the cardiac manifestation may precede the infectious disease symptoms, repeating the necessary examinations may be mandatory. PMID- 11760472 TI - NCLEX-RN strategies for success: a private university's experience. AB - Our university is committed to teaching excellence and effective student learning. To demonstrate this effectiveness, our school of nursing conducted a pilot study to assess the status of student learning through documented success on the National Council Licensure Examination for Registered Nurses (NCLEX-RN). Recognizing that recommendations on NCLEX-RN test plan development and revisions are based on results of the triennial RN job analysis study, it became apparent to faculty for the need to identify and enhance nursing skills a student should be able to perform at the entry level of a newly licensed registered nurse. Predictive variables were identified and correlated with outcomes on the NCLEX RN. Recommendations for research, education, and practice were developed and implemented leading to 1999 quarterly increases of 5-10% in NCLEX-RN scores. PMID- 11760473 TI - The dissertation ... and beyond: developing your academic career. AB - Completing the dissertation is not the end of a long journey; instead, it is the beginning of a journey that offers unlimited adventure. That adventure unfolds to become the individual's academic career. The skill with which that trip is planned can mean the difference between a challenging, but rewarding career or years of floundering and frustration. The road to the dissertation involves at least six traveling companies: the student, their mentor/dissertation chair, and the dissertation committee members. Careful selection of the dissertation chair is the first step to the successful completion of the dissertation. Forging that career-long partnership must be one of mutual benefit. Tips to aid in that selection are presented. Each committee member should be selected for their expertise and ability to support some aspect of a student's dissertation research. Strategies for the selection and evaluation of committee members are outlined. Finally, advice is offered on how to fund your dissertation research, enhance your scholarly development--pre- and post-doctorally, and seek post doctoral opportunities. PMID- 11760474 TI - The nursing process: what do students know? AB - The purpose of this study was to assess students' knowledge and understanding of the nursing process in preparation for the NCLEX-RN examination. A descriptive correlational research design was used. Fifty-one students in both associate degree and bachelors degree programs in an urban public university, participated in the pilot study. A survey tool was developed which asked students to define and give examples of the steps in the nursing process. Short answer responses were required. Students did not consistently give correct definitions and examples. A second study was developed to determine if students performed differently on a short answer examination and a multiple choice examination. Ninety-five students in both associate degree and bachelors degree programs participated in the second study. Students did more poorly on the multiple choice examination than on the short answer survey. Students in the pilot study performed better in some areas compared to students in the follow-up study. PMID- 11760475 TI - Mentoring: a supporting act for African American students and faculty. AB - Part of the reason for the low numbers of African-America nurses is related to nursing student attrition. One approach described to help students to successfully complete educational objectives is mentoring. Mentoring is a supportive act for both minority students and faculty. Although numerous definitions of mentoring exist it is recognized that a mentor can be a role model, confidante, friend, and support system. Mentors may be the passageway into the work force or a bypass around the many obstacles that impede success. Because of the limited African American faculty available, many are overworked and may never reach full potential, contributing to the problem of limited minority nursing faculty available to institutions of higher learning. This article describes the markers of both poor and positive mentoring universities. PMID- 11760476 TI - [Multiple organ failure--light at the end of the tunnel?]. PMID- 11760477 TI - [Multiple organ failure. Mechanisms, clinical manifestations and treatment strategies]. AB - Multiple organ failure (MOV) still represents the leading medical and economical problem in the care of the critically ill surgical patient. Although the incidence of MOF has tended to decrease over the last several years reflecting improved surgical and supportive therapy in the ICU, prognosis still remains serious when MOF develops. MOF seems to reflect a dysregulation of host-defence systems, such as innate immune, coagulation and complement systems, which are likely to reflect a more general dysregulation of cellular and subcellular functions, such as signal transduction and stress gene expression. Besides complexity and redundancy of the mediator systems involved, their beneficial local reparative as opposed to detrimental systemic effects may have contributed to the disappointing results of anti-mediator strategies in the treatment of MOF and sepsis. Although treatment of the underlying disease remains the cornerstone of the care of the critically ill patient to prevent MOF, recent results indicating a decreased mortality in severely septic patients receiving activated protein C as a supportive treatment suggest that modulation of the mediator cascades of sepsis and MOF remains a generally promising therapeutic strategy. PMID- 11760478 TI - [Less pain on injection by a new formulation of propofol? A comparison with propofol LCT]. AB - BACKGROUND: Pain on injection is a major disadvantage of propofol, experienced by the vast majority of patients. Since the traditional formulation has almost normal osmolality and pH, it is hypothesised that the concentration of free propofol in the aqueous phase of the emulsion is responsible for the pain and that reducing the amount of free propofol would also reduce the frequency and intensity of pain on injection. This study was designed to investigate whether pain on injection can be reduced in frequency and intensity by a new formulation of propofol. METHODS: We performed a monocentre, controlled, randomised, double blind study to compare the pain produced by intravenous injection of a new propofol preparation (propofol-MCT/LCT) with standard propofol in patients undergoing elective surgical procedures. A total of 184 non-premedicated patients received either 1% propofol prepared in a mixture of medium and long chain triglycerides (Propofol-MCT/LCT, Propofol- Lipuro, B. Braum Melsungen AG) or standard 1% propofol prepared exclusively in long chain triglycerides (Propofol LCT; Disoprivan, AstraZeneca) into a vein of the dorsal hand for induction of anaesthesia. Anaesthesia was maintained by TIVA with propofol and remifentanil. Pain on injection was recorded and graded as none, mild, moderate or severe. RESULTS: Patients receiving propofol-MCT/LCT had a significantly lower incidence of pain on injection compared to the standard propofol group (37% vs 64%) with the intensity of pain also being less severe. There were no differences between both groups in propofol dosage for induction (3.2 +/- 0.8 mg/kg vs 3.3 +/- 0.9 mg/kg) and maintenance of anaesthesia (3.4 +/- 0.6 mg/kg/h vs 3.2 +/- 0.5 mg/kg/h), remifentanil dosage (25 +/- 6 micrograms/kg/h vs. 24 +/- 6 micrograms/kg/h), intraoperative hemodynamics, recovery parameters and postoperative patient satisfaction. Postoperative thrombophlebitis at the injection site for propofol was not observed in any of the patients. CONCLUSIONS: Propofol-MCT/LCT produced significantly less pain on injection when compared to standard propofol in ASA I and II patients undergoing elective surgery. Pain was also significantly less severe, with both effects presumably being due to the lower concentration of free propofol in the MCT/LCT-preparation. With regard to injection pain propofol-MCT/LCT offers significant a advantage over standard propofol. PMID- 11760479 TI - [Patient surgical masks during regional anesthesia. Hygenic necessity or dispensable ritual?]. AB - OBJECTIVE: The use of surgical face masks (SFM) is believed to minimize the transmission of oro- and nasopharyngeal bacteria to wounds and surgical instruments. However, there are disadvantages for patients undergoing regional anaesthesia and wearing masks: deficient assessment of lip cyanosis, anxiety, retention of CO2, costs. Up to now no studies have been published investigating whether or not SFMs, worn by patients during regional anaesthesia, will reduce bacterial convection. METHODS: We investigated 72 patients during aseptic operations: 24 individuals with regional anaesthesia and SFMs, 22 individuals with regional anaesthesia without SFMs and 26 patients undergoing general anaesthesia. Using an air sampler (volumetric impaction method) 100 L air were collected on blood agar over 2 min. After incubation at 37 degrees C over 60 h the colony forming units (CFU) were counted and differentiated. Airborne culturable bacteria were sampled over the operation field, on the anaesthetic side of the surgical curtain, as well as 10 cm before and to the side of the patients mouth. RESULTS: At all 4 locations there were no significant differences in the number of CFUs between patients wearing a SFM or not (e.g. over the operation field: patient with SFM 5.5 +/- 1.1; no SFM 4.8 +/- 1.2; mean +/- SEM). Significantly more CFUs were detected in patients undergoing general anaesthesia (p < or = 0.05). The extent of the operation did not correlate with the number of CFUs; however, we observed a trend that more CFUs were detected with an increasing number of persons working in the operating room. CONCLUSION: Surgical face masks worn by patients during regional anaesthesia, did not reduce the concentration of airborne bacteria over the operation field in our study. Thus they are dispensable. A higher airborne germ concentration has been detected in patients during general anaesthesia. The reasons for this finding are unknown, but it may be discussed as being a result of a higher activity and number of staff involved during general anaesthesia causing more air turbulence. PMID- 11760480 TI - [Postpartum neurologic complications following delivery with peridural analgesia. Case report with literature review]. AB - Regional analgesia provides effective pain relief during delivery. Postpartal neurological deficits may be due to pressure of the fetal head on nerve structures at the pelvic rim or may be a complication of epidural analgesia. Nerve injuries due to spontaneous delivery and instrumental delivery are much more common than neurological deficits from epidural analgesia such as epidural hematoma or epidural abscess. The pattern of nerve damage is usually unilateral and non segmental. This case report describes the differential diagnosis of neurological deficit after spontaneous delivery under epidural analgesia and a discussion of the recent literature. Finally recommendations for the treatment of neurological deficits after delivery under epidural analgesia are presented. PMID- 11760481 TI - [Snakebite---intoxication by cobra venom]. AB - A private reptile breeder who handled exotic snakes was bitten by a Cobra near his ear. An ambulance was immediately called and the patient was transferred under unstable hemodynamic conditions to the nearest major hospital. During transport the patient had to undergo cardiopulmonary resuscitation. In the hospital, his status again deteriorated and he was intubated at a Glasgow coma scale of 5 and vasoactive medications were given. The patient was transferred by helicopter to a university hospital, where several doses of antivenom were given. After 4 days of deep coma the patient regained consciousness and spontaneous respiration and was extubated. Around the location of the bite wound angioedema and local necrosis developed. Surgical treatment of the wound was not necessary and 8 days after the incident the patient was fully recovered and was discharged from the hospital. PMID- 11760482 TI - [Latex allergy. Perioperative management in anesthesia and cardiac anesthesia]. AB - The frequency of perioperative allergic responses to latex has markedly increased over the last 10 years. High risk groups to develop sensitivity to latex include healthcare workers, workers in the latex industry, children suffering from congenital malformations such as spina bifida or urogenital deformities and patients who have undergone multiple surgical procedures. During surgery, patients have contact to a variety of products containing latex. To prevent anaphylactic reactions, all hospitals have to develop strategies to identify and manage patients sensitised to latex or belonging to high risk groups. The aim of this paper is to describe safe perioperative management in a latex-free environment. PMID- 11760483 TI - [Early contributions from Erlangen to the theory and practice of general anesthesia with ether and chloroform. 2. The animal experiments of Ernst von Bibra and Emil Harless]. AB - Just three months after the first application of sulphuric ether to a patient in german-speaking countries the monography Die Wirkung des Schwefelathers in chemischer und physiologischer Beziehung was published. In this book Ernst von Bibra and Emil Harless presented their experimental research on the effects of ether on humans and compared it to those on animals. The contents of the book are described. The authors "Theory on the action of ether" will be discussed in the context of contemporary criticism. Their hypothesis affected the discussion on the mechanisms of anaesthetic action up to the twentieth century. PMID- 11760484 TI - [The new international guidelines for cardiopulmonary resuscitation. Remarks on the article of V. Wenzel at al., Anaesthesist (2001) 50: 342-357]. PMID- 11760485 TI - [Epileptoform EEG activity: occurrence under sevoflurane and not during propofol application remarks on the article of B. Schultz et al., Anaesthesist (2001) 50:43-45]. PMID- 11760486 TI - [Emergency management in near-drowning and accidental hypothermia]. PMID- 11760487 TI - The epidemiology of fatalities reported to the vaccine adverse event reporting system 1990-1997. AB - PURPOSE: To examine the fatalities reported to the federally administered Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, in its first 7 years. METHODS: The working data set included variables such as demographic information, dates of vaccination, adverse event onset and death, vaccines administered, and vaccination facility data. Frequencies for these data and state reporting rates were calculated. RESULTS: A total of 1266 fatalities were reported to VAERS during July 1990 through June 1997. The number of death reports peaked in 1992-1993 and then declined. The overall median age of cases was 0.4 years, with a range of 1 day to 104 years. Nearly half of the deaths were attributed to sudden infant death syndrome (SIDS). CONCLUSIONS: The trend of decreasing numbers of deaths reported to VAERS since 1992-1993 follows that observed for SIDS overall for the US general population following implementation of the 'Back to Sleep' program. These data may support findings of past controlled studies showing that the association between infant vaccination and SIDS is coincidental and not causal. VAERS reports of death after vaccination may be stimulated by the temporal association, rather than by any causal relationship. PMID- 11760488 TI - Antihypertensives and myocardial infarction risk: the modifying effect of history of drug use. AB - PURPOSE: Confounding by indication is common in observational studies of outcomes that treatment is intended to affect. In light of the stepped-care approach to hypertension management, we reexamined the controversy around myocardial infarction (MI) risk in relation to antihypertensive agents by considering past drug history both as a confounder and as an effect modifier. METHODS: Case control design nested within a cohort of 19,501 adults initiating therapy with angiotensin-converting enzyme inhibitors (ACEI), calcium channel blockers (CCB) or beta-blockers in Saskatchewan (1990-93) and followed up to 1997. MI cases were identified using death certificates and hospital discharge diagnoses (ICD-9,410). Four controls were matched to each case to account for duration and timing of follow-up. RESULTS: 812 MI cases were identified, of which 26% were fatal. At first, current use of CCB and ACEI (versus beta-blockers) appeared to be associated with an increased risk of MI (RR = 2.2; 95% CI = 1.8-2.7 and RR = 1.3; CI = 1.0-1.6 respectively). Adjustment for drug use history attenuated both associations (RR = 1.6; CI = 1.1-2.2 and RR = 1.0; CI = 0.7-1.4). Moreover, the risk for CCB use disappeared when restricted to patients who had already used these agents in the past (RR = 1.1; CI = 0.77-1.7) whereas a high risk of MI for ACEI was found in digoxin users (RR = 9.4; CI = 3.2-27.5). CONCLUSION: Past drug history can be both a confounder and an effect modifier in observational studies. We found adjustment for medication history to attenuate the associations between antihypertensive agents and MI risk. In addition, the estimates significantly varied across drug history profiles thus suggesting the presence of preferential prescribing of specific drug classes to high-risk patients. PMID- 11760490 TI - Compliance in European pharmacovigilance: a regulatory view. PMID- 11760489 TI - Impact of the Minimum Pricing Policy and introduction of brand (generic) substitution into the Pharmaceutical Benefits Scheme in Australia. AB - PURPOSE: To describe the effects of introducing the Minimum Pricing Policy (MPP) and generic (brand) substitution in 1990 and 1994 respectively on the dispensing of Pharmaceutical Benefits Scheme (PBS) prescriptions both at the aggregate and individual patient level. METHODS: The relative proportion of prescriptions with a brand premium and those at benchmark was examined 4 years after introduction of the MPP and again 5 years later after generic substitution by pharmacists was permitted. To determine the impact of a price signal at the individual level, case studies involving a patient tracking methodology were conducted on two drugs (fluoxetine and ranitidine) that received a brand premium. RESULTS: From a zero base when the MPP was introduced in 1990, there were 5.4 million prescriptions (17%) dispensed for benchmark products 4 years later in 1994. At this stage generic (brand) substitution by pharmacists was then permitted and the market share of benchmark brands increased to 45% (25.2 million) by 1999. In the patient tracking studies, a significantly lower proportion of patients was still taking the premium brand of fluoxetine 3 months after the introduction of a price signal compared with patients taking paroxetine which did not have a generic competitor. This was also the case for the premium brand of ranitidine when compared to famotidine. The size of the price signal also had a marked effect on dispensing behaviour with the drug with the larger premium (fluoxetine) showing a significantly greater switch away from the premium brand to the benchmark product. CONCLUSIONS: The introduction in 1990 of the Minimum Pricing Policy without allowing generic substitution had a relatively small impact on the selection of medicines within the Pharmaceutical Benefits Scheme. However the effect of generic substitution at the pharmacist level, which was introduced in December 1994, resulted in a marked increase in the percentage of eligible PBS items dispensed at benchmark. Case studies showed a larger premium resulted in a greater shift of patients from drugs with a brand premium to the benchmark alternative. PMID- 11760491 TI - Risk factors for the development of Clostridium difficile toxin-associated diarrhoea: a pilot study. AB - This study was a pilot investigation of risk factors for the development of Clostridium difficile toxin-associated diarrhoea and in particular the differential influence of antimicrobial agents. The study was a retrospective case-control design conducted at Freeman Hospital, Newcastle upon Tyne. Cases were inpatients with stool positive C. difficile toxin diarrhoea and two controls were drawn for each case matched for age (+/- 5 years) and type of admission (emergency or elective). Using conditional logistic regression analysis, cephalosporins and erythromycin were found to be statistically significantly associated with Clostridium difficile toxin associated-diarrhoea. The results form the basis for designing a larger, prospective study. PMID- 11760492 TI - Trends in primary care antibiotic prescribing in England 1994-1998. AB - PURPOSE: To investigate the changing decisions to prescribe antibiotics as manifest in the patterns of prescriptions dispensed in England, and to investigate antibiotic prescribing in different types of practice. METHODS: Antibiotic prescribing data and practice characteristics collected for every practice in England for the years 1994/5-1997/8. Morbidity data for common infections was also obtained from published sources. RESULTS: Antibiotic prescribing was related to practice characteristics, with high prescribing in deprived and single-handed practices in particular. There was a fall in antibiotic prescribing in all types of practice of practice over the period of the study. Morbidity data from other sources shows a fall in diagnosed morbidity from some infectious diseases over the same period. There were no differences in choice of antibiotic in different types of practice. CONCLUSIONS: The fall in antibiotic prescribing is universal across all kinds of practices and is possibly related to the fall in diagnoses. It is uncertain whether this reflects true morbidity. PMID- 11760493 TI - The use of anti-asthmatic drugs in children: results of a community-based survey in Germany. AB - PURPOSE: To describe the use of anti-asthma drugs in children in the general population and in children with asthma using data from two large surveys in Germany. METHODS: Community-based random sample of 5-7 and 9-11-year-old children in Dresden and Munich were studied in 1995/96 by parental questionnaires using the Phase II protocol of the International Study of Asthma and Allergies in Childhood (ISAAC). A total of 11,094 children participated in the surveys (response rate 83%). RESULTS: In all children, inhaled beta 2-agonists were used most frequently during the last 12 months (2.6%), followed by inhaled cromolyns (2.5%), oral beta 2-agonists (1.5%), and inhaled steroids (0.9%). Drug use was significantly higher among boys than girls and in older children compared to younger ones (P < 0.05 for both). Among children with current asthma, 47% had used inhaled beta 2-agonists, 43% inhaled cromolyns, 22% oral beta 2-agonists, and 16% inhaled steroids. Inhaled steroids were used significantly more often in Dresden (21.7%) than in Munich (11.2%) (P < 0.05). CONCLUSIONS: Among anti-asthma drugs, agents used for symptomatic relief were the most frequently reported followed by inhaled anti-inflammatory agents. Most of the anti-inflammatory drugs used were SCG, which may indicate under-treatment with inhaled steroids. PMID- 11760494 TI - Use of cold medications for upper respiratory tract infections in children. AB - Prescribing practices in the treatment of upper respiratory tract infections (URTI) in children were studied, with particular emphasis on overuse of antibiotics, combination cold medications, and off-label use of medicines in children. Prescriptions with the diagnosis of URTI were studied over a period of 5 months in a general pediatric clinic. Out of 224 prescriptions scrutinized, a cold medication was prescribed in 88.4% of cases and 50.9% prescriptions contained a combination preparation. Antihistamines (50.9%), alpha-adrenoceptor agonist decongestants (50.0%) and opioid anti-tussives (24.5%) were the common ingredients of cold medications. Antihistamines (35.7%) were also used alone. Of the children 18.2% were receiving a drug contraindicated or not recommended in their age group. Antibiotics were prescribed in only 8.5% of cases, and for appropriate indications, reflecting a more restrained use of antibiotics. PMID- 11760496 TI - European pharmacovigilance legislation: has it led to implementation of pharmacovigilance inspections? PMID- 11760495 TI - Non-steroidal anti-inflammatory drug prescribing patterns in general practice: comparison of a general practitioner-based survey and a pharmacy-based survey in France. AB - PURPOSE: In order to assess biases occurring in primary care prescription studies, we compared non-steroidal anti-inflammatory drug (NSAID) prescribing patterns reported by general practitioners directly (GP-based survey) and from a pharmacy-based survey of general practitioner prescribing (pharmacy-based survey). METHODS: Volunteer GPs of the administrative area of Cote d'Or (France) returned a mailed questionnaire on NSAID prescribing patterns for consecutive patients seen during a 2-month period. In order to obtain a reference basis, pharmacies of the same administrative area provided all prescriptions that included NSAIDs during a 1-week period originating in general practice. RESULTS: The rate of participation was 25% for the GPs and 40% for the pharmacies. Participant GPs were representative of GPs of the area with regard to sex, year of graduation and practice area but pharmacies from rural areas were over represented. The GP-based survey and the pharmacy-based survey provided respectively 770 and 1050 prescriptions. There were no differences between either survey in the type of NSAIDs prescribed and in the most frequently associated drugs. GPs who volunteered in the GP survey prescribed NSAIDs more frequently orally and at higher doses than GPs involved in the pharmacy-based survey. They also prescribed more gastroprotective drugs, especially in the elderly. None of these results could be explained by differences in patient characteristics and GP practice areas. CONCLUSION: GPs who actively participate in prescription surveys exhibit prescribing patterns that fit better with official recommendations than the average. Although selection biases cannot be ruled out, it is suggested that some changes in GP prescription habits may have been induced by the survey itself. PMID- 11760497 TI - Propensity score methods in drug safety studies: practice, strengths and limitations. PMID- 11760498 TI - Pharmacoepidemiology and drug safety. PMID- 11760499 TI - HIV/AIDS: a world health tragedy. PMID- 11760500 TI - The impact of HIV/AIDS on the African American woman and child: epidemiology, cultural and psychosocial issues and nursing management. AB - The approach to understanding the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) must include the African American woman and children as persons at high risk. This information must be documented in all epidemiology, cultural and psychosocial aspects of care, and nursing management reports. Approximately twenty years after it was first recognized, AIDS is still traveling across the globe at full speed, with very little brake power. In the United States, the African American heterosexual woman continues to be the fastest growing group of persons with the acquired immunodeficiency syndrome. The proportion of cases increased drastically in the period from 1993 to October 1995, with women totaling 18 percent of the total cases (Newman & Wofsy, 1997). The impact that cultural and psychological issues have had on women and children living with HIV or AIDS is immense, involving not only the potential burdens of physical deterioration, but also the stress of accompanying lifestyle and role changes. These issues involve processes in adjusting and adapting to HIV infection that are important not only because of their centrality to the coping individual, but because they directly affect the success of treatment and prevention (Jaccard, Wilson & Radecki, 1995). PMID- 11760501 TI - Reducing the rate of mother-to-child HIV transmission in Africa. AB - Currently there are about twenty four million HIV/AIDS (human immunodeficiency virus and acquired immunodeficiency syndrome) cases on the continent of Africa. Over the past two years, many health care professionals have been in a stage of denial concerning this problem. According to researchers attending the XIII International AIDS Conference held in Durban, South Africa, the world became aware that cost-effective strategies are needed desperately to stop the rapid spread of HIV/AIDS in Africa. Recent studies suggest that modest antiretroviral drug therapies for HIV-positive pregnant women can reduce one-half of the risk of HIV transmission to the unborn child. Challenges to the governments of Africa such as the high cost of drugs, lack of health care infrastructure and cultural barriers, priority to treat only pregnant women has been a difficult decision, while other infected persons with HIV are not treated. PMID- 11760502 TI - Antiretroviral agents used in the treatment of HIV infections. AB - The human immunodeficiency virus (HIV) is a global problem in today's society. Presently, there is no cure for this devastating disease, but there are many treatment modalities from which to choose. The medications called antiretroviral agents must be carefully selected and customized for each person who is being treated for an HIV infection. Physicians and pharmacists must use extreme care when these drugs are ordered, because if they are used improperly, there will be an increase in resistance to the virus. In order to prevent resistance, people should be properly educated about these agents, how they should be taken, as well as the specific schedule to which they should comply. Education is the major factor in assisting with bringing this disease under control and reducing transmission. Antiretroviral agents recommended for HIV infection through the stages of reproduction, transmission, and treatment are discussed. PMID- 11760503 TI - Healthy People 2010. PMID- 11760504 TI - Finding business information and benchmarks for successful programs- BizhealthCheck.com. PMID- 11760505 TI - Benefits of a nurse directed over the counter medication dispensing system in an automotive plant. A preliminary study. AB - Information is limited about the effects of the availability of over the counter medicines (OTCs) at a worksite on workers' ability to remain at work and the effect on health care utilization. The purpose of this preliminary study was to assess workers' perceptions related to the benefits of having a nurse directed over the counter medication dispensing system (OTCMS) at an automotive manufacturing plant. Fifty-six percent of 257 randomly selected workers who participated in semistructured interviews indicated they used OTCs as the first intervention when at home, and 88% had obtained OTCs from the plant's medical department. The workers were overwhelmingly positive about having an OTCMS available at their worksite. Eighty-nine percent indicated that having OTCs available from the occupational health nurse made it possible for them to stay at work and complete their shift. Not only did the workers find the OTCMS to be an asset in their worksite, but they also highly recommended having an OTCMS available in work settings that do not presently have one in place. PMID- 11760506 TI - A collaborative model for employee health and nursing education. Successful program. AB - Combining the talents and skills of CON faculty and students with those of the CAVHS health professionals has demonstrated the synergy that can be obtained through collaboration. The health care needs of CAVHS employees continue to provide a fertile ground for the education, service, and research missions of the CON. The Program outcomes and employee satisfaction ratings, combined with the positive educational outcomes in the CON, have led to strengthened relationships between nursing education and the veterans health care system. The results of this partnership are illustrated by the recent signing of an additional 3 year contract for the CAVHS. PMID- 11760507 TI - Representation of work stress in an Australian public hospital. A case study. AB - Content analysis of the view of occupational stress presented in the Annual Reports of an Australian public hospital revealed scant attention to occupational health and safety issues and less still to the issue of workplace stress. The hospital aimed to "provide for all employees a working environment with maximum job satisfaction and opportunities for personal growth," yet stepped up surveillance of "sick leave not absolutely necessary or related to medical conditions." Investigation of the hospital's employee assistance programs revealed a "band aid" approach of individually focused stress management techniques rather than preventative organizational procedures. The researchers concluded that management considered workplace stress to be a problem in the employee not in the workplace, evident also in an increase of almost 1,000% in the number of clients visiting the staff counseling center in a 10 year period. Although a shift to focus on prevention was noticed in most recent reports consistent with the World Health Organization's target of stress prevention, the holistic public safety of workers appears an unmet challenge in this health industry. PMID- 11760508 TI - Positively channeling workplace anger and anxiety. Part I. AB - Negative emotions are not only a natural component of the world of work, they must be acknowledged and engaged if individuals are to make good decisions and if businesses are to create effective teams. Understanding that anger is a fear based emotion and that the brain is structured so anger and fear can be processed more quickly than rational thinking provides tremendous insights for occupational health personnel. Occupational and environmental health nurses can use the techniques presented in this article to develop employee self awareness and skills for positively channeling their workplace anger and anxiety. PMID- 11760509 TI - Anger and the use of nonviolent communication. PMID- 11760510 TI - Conducting research on the Internet--Part I. PMID- 11760511 TI - Expanding occupational and environmental health nurse resources. Using community projects to inspire volunteerism. AB - 1. Community involvement is becoming a natural extension of health and wellness services. Participation by occupational and environmental health nurses in community initiatives provides personal satisfaction, improves chapter cohesion, and increases visibility for the profession. 2. Variety in community projects enhances participation by appealing to the diversified interests and time constraints of members. 3. Volunteerism appeals to the basic beliefs of nurses helping to reach beyond individual health and wellness and target global issues. PMID- 11760512 TI - Roles and value added contributions of the occupational health nurse. Corporate perceptions. AB - This study replicated a study by Martin (1993) to examine the corporate perceptions of the current and future roles and activities of the occupational health nurse and the nurse's value added contributions in the local operating units of a large Fortune 100 company. A descriptive design was used for this study. The sample consisted of 44 corporate officials. The study findings are consistent with Martin (1993) and suggested that management is aware of the traditional roles and activities of the nurse, including direct care, education and counseling, and case management. The desired future activities identified were trend analysis, conducting plant rounds, and developing health programs specific to the needs of the corporation. The activities identified as adding value to the corporation included: planning and developing educational programs specific to the needs of the corporation, supervising the provision of nursing care, assisting in rehabilitation of injured workers, and providing follow up on workers' compensation claims. Corporate officials are aware of the traditional roles of the nurse. However, they may not be aware of the newer nursing roles, such as trend analysis, research, and budget development. PMID- 11760513 TI - Exposure risks and tetanus immunization in women of family owned farms. Implications for occupational and environmental health nursing. AB - A sampling pool of 4,808 farms in 10 parishes across southeast Louisiana was used to examine the risk factors of farm women who engage in activities putting them at risk for tetanus and to examine the circumstances related to vaccination. Data were collected, via stratified random sampling, in summer 1998 resulting in 657 completed interviews. Only 53.6% of women were current with a tetanus booster, having received their immunization within the past 10 years. Just as many women received tetanus vaccination following an injury or accident as for prevention. As women aged, they were less likely to be compliant. In the South, a number of environmental factors contribute to the risk for tetanus exposure and infection. These risk factors were examined in light of compliance with tetanus booster compliance. Increasing awareness of risk is essential because although tetanus is uncommon, the death rate from tetanus is greater than 30%. PMID- 11760514 TI - Essentials of environmental health. Enhancing your occupational health nursing practice (Part I). AB - 1. The environment is a primary determinant of health status of individuals and communities. Environmental hazards are widespread and poorly understood. 2. The five parameters of exposure pathways for environmental hazards include source of contamination; environmental media and transport mechanism; point of exposure; route of exposure; and receptor population. Routes of exposure to environmental hazards include percutaneous (dermal); inhalation; ingestion, gastrointestinal tract; and transplacental. 3. Humans vary widely in their susceptibility to potential environmental hazards. The human response to environmental conditions varies with a variety of personal characteristics including age, weight, gender, nutritional status, psychological status, preexisting disease states, concomitant or previous exposures, and even behavior and lifestyle factors. 4. The unique knowledge and skills possessed by occupational and environmental health nurses make them an important resource for clients, community members, and other health care professionals. PMID- 11760515 TI - Volunteerism--It's history! PMID- 11760516 TI - Storytelling and violence against women. AB - Health professionals are frequently the first point of contact for many women who are abused and experience intimate male partner violence. Yet, practitioners often do not have the knowledge and/or feel prepared to address these issues with women. The authors propose the use of storytelling and literature as an educational strategy to challenge and change nurses' conceptualization and practices relative to abuse and violence against women. PMID- 11760517 TI - Self-reported health status and depression of battered black women. AB - This study examined the influence of psychological factors and personal characteristics on depression and health outcomes of battered Black women. Much of the existing research on violence against women by intimate partners has focused on prevalence and response to abuse. However, the problem of battering among Black women as a group has been neglected, especially as it impacts health and causes health-related problems. Secondary analysis was used in this study to look at health-related problems and battering. The sample consisted of 128 battered Black women who participated in interviews, and completed the Beck Depression Index, Health Response Scale, Daily Hassles Scale, and Index of Spouse Abuse. Study outcomes indicated a positive relationship between depression and gastrointestinal upsets. Further study with a larger group of women is needed to validate findings. PMID- 11760519 TI - A review of sex offender treatment programs. AB - The author analyzes the current literature and research concerning sexual offender treatment including research on treatment methods and a brief review of three populations: wife batterers; alcoholics; and substance abusers. A brief description of several treatment programs is followed by a discussion of sex offender treatment effectiveness, and a qualitative study of alcoholics' perception of treatment to illustrate how qualitative results were utilized to structure a treatment approach. PMID- 11760518 TI - Physical and psychological abuse among a predominantly African American sample. AB - The purpose of this descriptive correlational study was to explore the prevalence of physical and psychological abuse between intimate partners in a non-clinical sample of predominantly African American women. The self-administered questionnaire included: a) demographic characteristics, b) the Index of Spouse Abuse (ISA) designed to measure physical and psychological abuse c) the Family Violence Scale (FVS) designed to measure family history of violence and d) a question inquiring as to past history of sexual abuse and e) a question asking whether participants perceived that they were abused versus nonabused. Students, faculty and staff from a large midwestern urban commuter university with undergraduate and graduate programs were surveyed. A computerized random sampling procedure was used to select the sample. One hundred and seventy nine usable questionnaires were returned. The findings revealed a 15.6% rate of physical abuse, an 11.7% rate of psychological abuse and a 6% rate of both physical and psychological abuse among the sample. Women's perceptions of abuse (feeling abused versus not feeling abused) and the occupation of their partners (blue collar) accounted for most of the variance in physical (R2 = .32) and psychological abuse (R2 = .43). The findings have implications for expanding the practice of nursing to college campus populations to prevent, and intervene in issues of intimate partner abuse. PMID- 11760520 TI - Job security for the 21st century. PMID- 11760521 TI - Job security for occupational health and safety professionals in the 21st century. What you need to know about the institute of medicine (2000) report. AB - The IOM study does an admirable job of discussing trends affecting the future of workers and the workplace. Based on theses trends, there will be vast unmet needs, as well as tremendous opportunities, for occupational health and safety professionals, particularly occupational health nurses, to help meet these needs. Individual occupational health and safety professionals will do well to study the trends, assess their current knowledge and skills, and seek the education and training required to develop and enhance the necessary competencies. They will need to: pay special attention to areas of behavioral health, work organization, communication (especially risk commnication), management, team learning, work force diversity, information systems, prevention interventions, health care delivery systems, and evaluation methods (IOM, 2000). They will need to develop, document, and communicate new and creative models for providing occupational health and safety services. Also, see the Advisory, "Job Security for the 21st Century," on page 164A. PMID- 11760522 TI - Disability management. Application of a nurse based model in a large corporation. AB - 1. Minimizing the impact of injury, disability, and disease on employees is important not only to enhance the employee's quality of life, but also to maintain worker performance. Key to the disability management plan is early, aggressive, and safe return to work programs, which minimize personal and corporate costs. 2. The challenge is to improve the delivery of various disability programs (including short term disability, long term disability, and workers' compensation), and minimize escalating costs. 3. Program development provides the foundation for a disability management system. Implementation is key to achieving success. To successfully market case management, the occupational health nurse must articulate the cost benefit, as well as other concepts behind case management. 4. Disability management can be operationally defined as an active process for minimizing the impact of an impairment (resulting from injury, illness, or disease) on the individual's capacity to participate competitively in the work environment. PMID- 11760523 TI - The process and results of departmental specific safety surveys for health care organizations. Successful program. AB - 1. Meeting compliance and accreditation standards can be challenging for any organization, especially in the health care setting. Safety surveys can play a strategic role in proactively preparing for such events. 2. Implementing department specific safety surveys offers a tailored approach to monitoring and addressing the occupational safety issues that occur within each department. 3. Safety surveys are a method for assessing and monitoring the environment and employee training needs, and for driving safety decisions. 4. Safety in the workplace must be a shared and continuous responsibility among employees. A formal safety survey process instilling a culture of responsibility and "buy in" by all employees is necessary. PMID- 11760524 TI - Essentials of environmental health. Enhancing your occupational health nursing practice (Part II). AB - 1. In the United States, approximately 24 million people use water daily from unregulated water supplies. Agents of water pollution can be categorized as biological (e.g., Cryptosporidium parvum), chemical (e.g., industrial solvents), or radionuclide (e.g., radon). 2. More than 600 chemicals are registered with the Environmental Protection Agency as pesticides in the United States. Human exposure occurs through direct contact or dermal absorption, inhalation, and ingestion of food, water, and breast milk. It is estimated that 50% of all the pesticides ingested in a lifetime are ingested in the first 5 years of life. 3. Children are at particular risk for exposure to environmental toxicants like pesticides because of time spent crawling and playing on floors, lawns, and other potentially contaminated surface areas, and hand to mouth behaviors. At this time, toxicity data for many pesticides in common use are inadequate to determine potential for neurotoxicity and adverse effects on the developing immune and endocrine system. 4. To meet the challenge of environmental health issues, occupational and environmental health nurses have important opportunities to promote health in the workplace and the community through research, direct clinical services, advocacy, and education. PMID- 11760525 TI - Conducting research on the Internet--Part II. PMID- 11760526 TI - The art of strategic planning. Creating the future path. PMID- 11760527 TI - The effect of injection speed on the perception of intramuscular injection pain. A clinical update. AB - Injections are frequently administered by occupational health nurses in worksite health promotion programs. The purpose of this study was to examine the effect of varying injection speed on the perception of pain. Fifty workers were given intramuscular (i.m.) hepatitis B vaccine at injection speeds of 10 and 30 seconds per cubic centimeter (s/cc). The perception of pain was measured on a visual analogue scale and reported post-injection at three different time intervals. The results showed that no difference in pain was perceived by participants between the two injection speeds. Results also revealed that women consistently had higher mean pain scores than men and significantly more pain at the 0 hour measurement of the 10 s/cc injection. While the results of this study indicate no need to administer an i.m. injection slower than 10 s/cc, occupational health nurses will need to consider gender differences in pain perception when administering injections. PMID- 11760528 TI - Developing a Respiratory Protection Program. Understanding the written elements. AB - 1. Respirators can be the last defense for the estimated 5 million employees who use them for protection from dusts and fibers, fumes, mists, gases, vapors, and biological hazards. Because of these potentially lethal respiratory hazards, occupational and environmental health nurses need to be able to determine the need for, understand, develop, update, and implement an actionable respiratory protection program (RPP). 2. Regulated per 29 CFR 1910.134, a written RPP becomes the map or guideline process specific to the workplace that needs to be followed to ensure employee protection. 3. The nine required written elements of a RPP include respirator selection; fit testing; respirator use in routine and emergency situations; respirator maintenance and change schedules; ensuring adequate breathing air supply, quantity, and flow for atmosphere supplying respirators; regular evaluation of program effectiveness; medical evaluation; training employees in the respiratory hazards in routine and emergent situations; and training employees in proper use of the respirator. 4. Occupational and environmental health nurses are in a unique position to be a RPP program administrator, its designated licensed health care professional, or an active member of a team implementing the RPP process. PMID- 11760529 TI - Absence monitoring. A case management perspective. AB - 1. A need for absence monitoring was identified at a three facility complex. The company's direct and indirect costs for nonoccupational absences exceeded costs of occupational absences. 2. Occupational health nurses gained management support for a proactive absence monitoring program. 3. An absence monitoring program was developed and implemented using a case management approach. 4. Quantitative analysis revealed the program was well received by employees and valued by management. The data also proved the program was cost effective. PMID- 11760530 TI - Telecommuting. Factors to consider. AB - 1. Telecommuting is a work arrangement in which employees work part time or full time from their homes or smaller telework centers. They communicate with employers via computer. 2. Telecommuting can raise legal issues for companies. Can telecommuting be considered a reasonable accommodation under the Americans With Disabilities Act? When at home, is a worker injured within the course and scope of their employment for purposes of workers' compensation? 3. Occupational and environmental health nurses may need to alter existing programs to meet the distinct needs of telecommuters. Often, there are ergonomic issues and home office safety issues which are not of concern to other employees. Additionally, occupational and environmental health nurses may have to offer programs in new formats (e.g., Internet or Intranet programs) to effectively communicate with teleworkers. PMID- 11760531 TI - The power of a vision. The nurse's journey through health care. AB - 1. Currently, health care is a constant battle between cost and compassion. The most difficult change health care professionals have had to make is expanding the vision of the compassionate caregiver to include the bottom line business professional. 2. Occupational and environmental health nurses need to have more visibility in the companies they work for to get a "seat at the table" with the rest of the management team. One way to gain visibility and credibility is to be a part of the community newsletter via a column "Ask the Nurse" where employees send in questions and nurses answer one or two questions each month. 3. Occupational and environmental health nurses can become the "visionaries" of the companies they work for by formulating a vision of what they want to provide for the employees of their companies and passionately sharing that vision with management and employees alike. If both management and employees buy into that vision, a remarkable transition can take place. 4. The future is very exciting for occupational and environmental health nurses. For those leaving the corporate world, there will be expanding opportunities in research, education, policy making, and lobbying. Occupational and environmental health nurses with the entrepeneurial spirit could consider being a consultant, working for a number of different companies, both here and abroad. PMID- 11760532 TI - Positively channeling workplace anger and anxiety. Part II. AB - Emotions are powerful, free resources for businesses. Just as employee enthusiasm is essential for superior productivity, anger can be harvested for peak performance. An array of psychological and physiological tools have been described to empower employees so they may constructively handle their anger, anxiety, and stress. These tools can be used to reduce health care and workers' compensation costs while creating an effective workplace in which angry outbursts or passive aggressive behavior is rare. Methods for de-escalating angry responses have also been described. Using these techniques can help ensure a nonviolent workplace while inducing a cooperative environment for problem solving and lowering the frustrations of employees. PMID- 11760533 TI - Coping with stress. PMID- 11760534 TI - [Endoscopic diagnostics of colorectal neoplasms]. PMID- 11760535 TI - [Tetracycline treatment, oral contraceptives and pregnancy]. PMID- 11760536 TI - [Depression, stress and brain function]. AB - Many patients with major depression have elevated serum cortisol, which cannot be suppressed with dexamethasone. This points to a disturbance in the hypothalamus pituitary-adrenal (HPA) axis, which might have pathogenetic importance. Recent investigations with MRI have shown an increased frequency of generalised, as well as localised atrophy in the brains of depressed patients. The reduced volume of the hippocampus is particularly interesting, because of the participation of this structure in the regulation of the individual's stress response. Furthermore, the hippocampus is of major importance for cognitive processes. There is evidence that the increased cortisol concentration is neurotoxic and may cause atrophy, as is known from Cushing's disease. This is supported by studies of the accumulated duration of depressive episodes, and also by the fact that drugs that dampen the HPA axis have proved to have antidepressant properties in clinical controlled, double-blind studies. This points to new principles in the treatment of major depression and underlines the importance of early intervention in order to prevent cerebral atrophy, which is probably reversible at the beginning of the disease process. PMID- 11760538 TI - [Laparoscopic cholecystectomy in outpatient surgery]. AB - INTRODUCTION: The aim of the study was to describe the organisation of laparoscopic cholecystectomy in outpatient surgery and to discuss whether the method should be the future treatment of choice. MATERIAL AND METHODS: A retrospective descriptive study was carried out on 133 consecutive patients in the period 1 October 1999 to 30 September 2000. RESULTS: Seventy-seven per cent of the patients were discharged directly from the Department of Outpatient Surgery and 121 (97%) who underwent laparoscopy were discharged within 23 hours of the operation. The postoperative complication rate was 1.5% and the frequency of readmittance was 5%. DISCUSSION: Laparoscopic cholecystectomy is suitable for outpatient surgery and appears to be a recommendable setting for this operation. The method is safe and associated with few complications and readmittances. PMID- 11760537 TI - [Sigmoidoscopy as primary examination in patients with bowel symptoms]. AB - INTRODUCTION: Flexible sigmoidoscopy is recommended in the literature and is now officially recommended as the primary diagnostic method in patients with symptoms consistent with colorectal cancer. Sigmoidoscopy can detect two-thirds of all colorectal cancers. MATERIAL AND METHODS: We carried out a retrospective analysis of prospective data on symptoms and findings at FS in 682 patients, above the age of 40 years, referred to a private specialist for rectal bleeding, change in bowel habits, or unspecific abdominal symptoms. The chi 2-test and logistic multivariate regression analysis were used to estimate the predictive value of symptoms for neoplasia. RESULTS: Carcinoma was found in 31 (5%) and adenoma in 76 (11%), i.e., neoplasia in 16%. Logistic multivariate regression showed that bleeding in or on the faeces (p < 0.0001, OR 10.6 and 11.6), mucous discharge (p = 0.02, OR 3.0), and change in bowel habits (p = 0.02, OR 3.0) were independent risk factors of cancer, and bleeding on the faeces (p = 0.0002, OR 3.2) or in the faeces (p = 0.02, OR 2.7) were independent risk factors of adenoma. DISCUSSION: On the basis of the literature and the present results, we conclude that sigmoidoscopy is a suitable primary diagnostic method for the detection of neoplasia in the rectum and left colon in patients with bowel symptoms. Bleeding, mucous discharge, and change in bowel habits are independent risk factors for carcinoma and bleeding for adenoma. PMID- 11760539 TI - [Evaluation of a leadership education at the Rigshospitalet. How an evaluation design can support organizational learning]. AB - INTRODUCTION: The aim of the present study was to evaluate a Management & Leadership Education and Training Programme at the hospital before, during, and after implementation, allowing stakeholders to qualify alteration of the Programme as a process by using for instance formative evaluation. MATERIAL AND METHODS: The Delphi method is used for pre-evaluation of the concept of the Programme. Pre- and post-questionnaires were employed to measure the participants' adaptation of the hospital's "Management Fundamentals" before and after the Programme. RESULTS: The Expert panel stated that the Programme concept was pertinent and applicable. One hundred per cent recommended the Programme to be interdisciplinary. Eighty-two per cent stated that it would probably be difficult to acquire organisational learning. The results of the pre- and post questionnaires showed that the participants and their superiors found that they adapted the hospital's "Management Fundamentals" better after having followed the Programme. DISCUSSION: With the use of the Delphi method (formative evaluation), the Programme concept could be altered already before implementation. The experts stated that they were not sure that the Programme would support organisational learning. Having this knowledge, it has been possible to work with activities supporting organisational learning already during implementation. In future, the experience with pre- and post-measurements will be used in a concrete way to support the learning environment in the organisation. PMID- 11760540 TI - [The relevance of mirror examination in modern otorhinolaryngology]. AB - INTRODUCTION: The aim of this study was to investigate whether the teaching of mirror examination of the larynx and rhinopharynx is still relevant and to estimate whether it is still a reliable examination. MATERIAL AND METHOD: Twenty five patients underwent a mirror examination of the larynx and rhinopharynx by a young doctor, a young otorhinolaryngologist, and a senior otorhinolaryngologist. RESULTS: Not surprisingly the senior otorhinolaryngologist conducted the most adequate examinations. Forty-three percent of the laryngoscopies were adequate, that is all anatomic structures were seen. Forty-one per cent provided a reasonable survey, that is a few anatomic structures were not seen. This shows that 84% of the laryngoscopies could be used to give a reasonable examination of the larynx. Only 27% of the rhinoscopies were completely adequate, and as many as 49% were inadequate. DISCUSSION: Routine mirror examination of the larynx adequately provides a reliable diagnosis in most patients. But in some, it is not adequate, and here fibrolaryngoscopy is a good alternative and a more reliable examination. Mirror examination of the rhinopharynx is difficult, so if a disease of the rhinopharynx is suspected, the patient must be given a fibroscopy and biopsy under general anaesthesia. PMID- 11760541 TI - [Staging of rectal cancer by means of MRI. Experiences with the first twenty-five patients]. AB - INTRODUCTION: The Danish Surgical Society recommends preoperative radiation for patients with T4 tumours of the rectum. However, the clinical examination with regard to fixation, especially for tumours in the upper part of the rectum, is encumbered by much uncertainty. MR imaging is a new modality in the staging procedure of the patient with rectal cancer. Our experience with the first 25 patients is presented. METHODS: After clinical examination, an MRI of the rectum was done and in the case of a T4 tumour preoperative radiotherapy was established. Preoperative MRI staging was correlated with the histopathology of the resection specimen. RESULTS: In cases of tumours in the lower third of the rectum, we found total agreement between the clinical examination and the MRI findings. In the middle third it was impossible to assess clinical fixation in two out of seven patients and in the upper third it was impossible in eight out of ten. With respect to possible involvement of lymph nodes, the MRI revealed a true positive diagnostic frequency of 0.78, a true negative diagnostic frequency of 0.92, a true positive nosographic frequency of 0.88 and a true negative nosographic frequency of 0.85. The corresponding values for tumour invasion were 0.94, 0.75, 0.94 and 0.75. DISCUSSION: Our results seem to indicate that preoperative MRI--especially in patients with tumours in the upper two-thirds of the rectum--is suitable for predicting fixation. MRI also seems to be suitable in the complete staging of the patient with a tumour of the rectum. PMID- 11760542 TI - [Examination and treatment of dyslipemia after myocardial infarction--are the goals achieved?]. AB - According to guidelines, medical treatment of dyslipidaemia in post-AMI patients should await assessment of underlying lipid disorders and the outcome of dietary treatment. The risk of patients not being treated with lipid-lowering therapy because of lack of follow-up has led to more aggressive guidelines recommending statin treatment even before discharge from hospital. In a study comprising 730 patients, we have shown that, although most patients were discharged from the coronary care unit without statin treatment, a traditional rehabilitation programme succeeded in assessing more than 95% of the patients for underlying lipid disorders, and more than 75% of patients with plasma cholesterol > or = 5.5 mmol/l received lipid-lowering therapy within the first year. Most patients were treated with statins. Statins, however, were given in smaller doses than those used in the clinical trials, and only 52% of the treated patients reached the recommended goal of plasma cholesterol lower than 5 mmol/l. PMID- 11760543 TI - [Risk factors of lower urinary tract symptoms in women aged 40-60 years]. AB - INTRODUCTION: The study was carried out to determine the relation between lower urinary tract symptoms and possible associated factors in women aged 40-60 years. METHODS: In a normal population study, 502 women with lower urinary tract symptoms and 742 women without symptoms (controls) were asked about possible associated factors. RESULTS: Four hundred and eighty-seven (97.0%) women with symptoms and 564 (76.0%) controls completed the study. Stress incontinence was associated with parity (primipara: OR = 2.2 [95% CI: 1.0; 4.9]; para II: OR = 3.9 [95% CI: 1.9; 8.0]; para III: OR = 4.5 [95% CI: 2.1; 9.5]), the use of diuretics (OR = 2.2 [95% CI: 1.2; 3.9]), hysterectomy (OR = 2.4 [95% CI: 1.6; 3.7]), and increased BMI. Urge incontinence was associated with the use of diuretics (OR = 4.0 [95% CI: 2.2; 7.1]) and increased BMI. Urgency was associated with parity (primipara: OR = 1.9 [95% CI: 0.9; 4.2]; para II: OR = 3.0 [95% CI: 1.5; 5.9]; para III: OR = 3.1 [95% CI: 1.5; 6.5]), the use of diuretics (OR = 2.7 [95% CI: 1.5; 4.7]) and increased BMI. Associations between non-incontinence symptoms (except urgency) and the factors studied were weak and inconsistent. Straining at stool and constipation were inversely associated with lower urinary tract symptoms. Overall, lesion of the anal sphincter, episiotomy, fetal weight, physical activity, and hormonal status had a minor, if any, association with lower urinary tract symptoms. CONCLUSIONS: Lower urinary tract symptoms were associated positively with parity, BMI, prior hysterectomy, use of diuretics, straining at stool, and constipation. PMID- 11760544 TI - [Recurrent mucineous cystadenoma in an 11-year-old premenarchal girl]. AB - A case of a recurrent ovarian mucinous cystadenoma in an 11-year-old, premenarchal girl is described. The treatment of choice was cystectomy, partly because of the patient's age and partly because malignancies are uncommon in this population. The operative approach can either be by laparotomy or laparoscopy when technically feasible. But it is important to keep in mind the possibility of recurrence even of benign cysts. PMID- 11760545 TI - [Picture of the month: foreign body in the respiratory tract]. PMID- 11760546 TI - [Anthrax. Description of symptoms, findings, diagnostics and treatment of infection]. PMID- 11760547 TI - [Anthrax transmission from patient to patient?]. PMID- 11760548 TI - [Is it smart to give immunoglobulin prophylaxis against respiratory syncytial virus infection?]. PMID- 11760549 TI - [Diabetic retinopathy--reply]. PMID- 11760550 TI - [Smoking, health education, questionnaires and science]. PMID- 11760551 TI - NCCN: Non-Hodgkin's lymphoma. PMID- 11760552 TI - NCCN guidelines development: Some lessons learned. PMID- 11760553 TI - NCCN: New directions in chronic lymphocytic leukemia. PMID- 11760554 TI - NCCN: Fever and neutropenia. PMID- 11760555 TI - NCCN: Non-small cell lung cancer. PMID- 11760556 TI - NCCN: Small cell lung cancer. PMID- 11760557 TI - NCCN: Chronic myelogenous leukemia. PMID- 11760558 TI - NCCN: High-dose chemotherapy. Applications of high-dose chemotherapy with bone marrow/stem cell support in solid tumors. PMID- 11760559 TI - NCCN: Breast cancer. AB - The 2001 NCCN Breast Cancer Guidelines reflect the results of 5 generations of NCCN Breast Cancer Guidelines. Evidence-based guidelines, such as the NNCN Breast Cancer Guidelines, are possible only because of the availability of high-level evidence at multiple decision points in treatment. The continued performance of high quality clinical trials is central to our ability to further improve the treatment of breast cancer. The panel believes that participation in high quality clinical trials is the preferred treatment at all points in breast cancer therapy. PMID- 11760560 TI - NCCN: New chemotherapeutic approaches to hormone refractory prostate cancer. PMID- 11760561 TI - NCCN: Palliative care. PMID- 11760562 TI - NCCN: New applications for erythropoietin. PMID- 11760563 TI - NCCN: Multiple myeloma. AB - Although multiple myeloma is sensitive to both chemotherapy and RT, it remains incurable at present. However, treatment algorithms based on published data, as well as clinical experience, can be developed to optimize therapy. This includes not only therapy for the underlying disease but also supportive therapy to enhance quality of life. Because myeloma is incurable, these guidelines prominently identify the clinical settings appropriate for treatment of patients on clinical research protocols. PMID- 11760564 TI - NCCN: Distress management. PMID- 11760565 TI - NCCN: Sarcoma. PMID- 11760566 TI - Cancer and aging: why not waltz together? AB - The burden of cancer is felt disproportionately among the elderly with the majority of cancers occurring in adults over the age of 65. Dr. Bennett briefly examines the implications of this fact, and acknowledges the growing evidence that clinicians are ill equipped to handle the complex management issues of their elderly patients. CA will continue this series on geriatric oncology in future issues. PMID- 11760567 TI - Comorbidity considerations in geriatric oncology research. AB - Although it is generally acknowledged that comorbidity has a significant impact on treatment selection and outcomes for elderly patients with cancer, an understanding of how comorbid conditions should influence clinical decisions is quite incomplete. This issue remains an important and challenging area of geriatric oncology research. Measures of comorbidity require recognition, documentation, and accurate data extraction. Extensive prospective evaluations and medical chart reviews have the greatest reliability but are costly. Administrative data are convenient and applicable to large populations, but suffer from relatively poor reliability and therefore should be used with caution. Perhaps in the future more refined nosology and better information systems will improve our understanding and ability to use administrative data sets to study comorbidity in the elderly--the eventual goal of such investigation being evidence-based criteria for care of elderly cancer patients. PMID- 11760568 TI - Radon. AB - Residential and occupational exposure to radon is the second leading cause of lung cancer after cigarette smoking. As many as eight million homes in the US have elevated radon levels according to Environmental Protection Agency estimates. High exposure levels in homes are largely a result of radon contaminated gas rising from the soil. This makes it an unusual indoor air pollutant in that it has a natural source. This study examines the synergism between smoking and radon, what levels are considered safe, and what to do to safeguard against overexposure to radon. PMID- 11760569 TI - Epidemiology and molecular pathology of gallbladder cancer. AB - Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis. We report here the worldwide geographical distribution of gallbladder cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5-15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans. The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high-risk populations. Secondary prevention of gallbladder cancer could be effective if supported by cost-effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high-risk areas. PMID- 11760570 TI - Important facts about cancer pain treatment. PMID- 11760571 TI - Geographic variation in breast cancer mortality for white and black women: 1986 1995. AB - Breast cancer mortality rates have decreased during the last 20 years in the United States overall. However, declines in breast cancer mortality rates differ among individual states. This analysis ranked states from the highest to the lowest percentage change in mortality between 1986 to 1990 and 1991 to 1995. Data on white and black females were analyzed separately. Among white women, the 10 states showing the greatest percentage change in mortality during those two periods had the greatest baseline mortality in the 1986-to-1990 period. Similarly, the 10 states with the lowest percentage change in mortality had the lowest mortality rate in 1986 to 1990. In contrast, among black women, the top 10 states ranked by percentage change in mortality included either a decline or an increase. The disparities in mortality rates by state likely depend on the stage of disease at diagnoses, socioeconomic status, access to care, and adequacy of medical care. PMID- 11760572 TI - [Revised nomenclature for medical acts]. PMID- 11760573 TI - [Portal vein embolization prior to hepatectomy. Techniques, indications and results]. AB - Postoperative liver failure is a severe complication of major hepatectomies, in particular in patients with a chronic underlying liver disease. Preoperative interruption of the portal flow in the liver territories planned to be removed, induces their atrophy and the compensatory hypertrophy of the segments spared by the resection. This interruption can be induced by the surgical ligation of the portal branches or by the percutaneous intraportal injection, under ultrasound guidance, of glues or sclerosing agents. Preoperative portal vein embolisation is usually indicated when the remnant liver accounts for less than 25-40% of the total liver volume. Feasibility is close to 100% and the risk comparable to that of a percutaneous liver biopsy. It is well tolerated and the biological impact is minimal in patients without liver failure. Compensatory hypertrophy of the non embolised segments is maximal during the first 2 weeks and persists, although to a lesser extent during approximately 6 weeks. The magnitude of hypertrophy is correlated with the volume of parenchyma embolised, and is reduced in diabetic or jaundiced patients or when there is an active chronic liver disease. Liver resection is performed 2 to 6 weeks after embolisation. Retrospective studies and one prospective study suggest that patients so prepared have a reduced perioperative risk and that their long term carcinologic results are not impaired. PMID- 11760574 TI - [Consensus conference. Treatment of hemorrhoidal diseases]. PMID- 11760575 TI - [Is preoperative localization of insulinomas necessary?]. AB - STUDY AIM: To appreciate the impact of preoperative localization in surgical treatment of insulinomas. PATIENTS AND METHOD: From 1986 to 2001, 29 patients were surgically treated for suspected insulinoma. Preoperative imaging assessment was performed in 26 patients: ultrasonography (n = 21), computed tomography (n = 23), endoscopic ultrasonography (n = 13), intraoperative ultrasonography (n = 22) (2 of them under laparoscopic approach). RESULTS: The sensibility of the localization procedures was as follows: ultrasonography = 9.6%, computed tomography = 39%, endoscopic ultrasonography = 92.3%, surgical exploration 79.3%, intraoperative ultrasonography 86.3%. The sensibility of intraoperative palpation associated which intraoperative ultrasonography was 100%. Surgical procedures included: 11 enucleations, 10 segmental resections of the tail, 1 left pancreatectomy, 3 median pancreatectomies, 4 subtotal pancreatectomies. There was no postoperative mortality and postoperative morbidity rate was 17%, including 4 pancreatic leakages. Histological examination found solitary tumor in 22 patients (1 of them was a malignant tumor), multiple tumors (MEN 1) in 4 patients and factitious hypoglycemia in 3 patients. All the insulinomas were resected. CONCLUSION: Intraoperative evaluation of the pancreas with intraoperative ultrasonography was associated which a right localization in 100% of insulinomas. The place for preoperative imaging seems to be limited. A laparoscopic approach in sporadic insulinomas could modify this attitude. PMID- 11760576 TI - [Vascular deficit is the major cause of fistula in esophageal surgery]. AB - AIM OF THE STUDY: The aim of this retrospective study was to find a link between vascularization failure and fistula in esophageal surgery. The originality of this study was to be based on hyperselective arteriogaphy of the artery vascularizing the gastric plasty, showing all vascular network of the plasty. PATIENTS AND METHODS: Hyperselective arteriography was carried out in 14 patients operated for esophagus cancer with a gastric plasty replacement. All these patients had a postoperative leakage or a bad vascularization of the gastric plasty during the operation. RESULTS: The vascularization of the gastric plasty was organized from the gastro-epiploic artery by anastomotic transversal network, depending on the left gastro-epiploic artery and left gastric artery. For the 14 patients, a constant link between leakage and vascularization failure could be proved. CONCLUSION: Esophageal surgery is dependent on the vascular status of the patient. The type of gastric plasty with large or narrow tubulization does not interfere with the quality of vascularization at the top of the plasty due to the preservation of a corporeal low branch. PMID- 11760577 TI - [Isolated pancreatic neck rupture]. AB - AIM OF THE STUDY: Through four cases of pancreatic neck rupture, the study aim was to emphasize the advantages of an early laparotomy when there is a doubt about a canal disruption and the risks of a later surgical management. PATIENTS AND RESULTS: Four patients were operated on for a neck disruption of the pancreas due to blunt trauma. Two patients underwent laparotomy in the first 48 hours after a radiological exploration and underwent a left pancreatectomy with spleen preservation. There were no associated injuries, no lesions of acute pancreatitis. The two other patients were, at first, medically treated and developed an acute pancreatitis with pseudocyst. They underwent laparotomy, 7 and 10 days after the trauma because of pain and hyperthermia, and a conservative treatment by cystojejunostomy was performed in difficult conditions because of the acute pancreatitis. A late pancreatic pseudocyst (4 and 6 months) occurred in two patients. CONCLUSION: When pancreatic trauma occurs, an exploration with echography, scanner, endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography can suggest a neck disruption and a canal rupture. When the canal is safe, a drainage close to the pancreas is sufficient. When the rupture of the canal is suspected or proved, an early laparotomy is necessary in order to investigate the pancreas and to perform the appropriate procedure. This surgery is easier before the occurrence of pseudocyst and acute pancreatitis. PMID- 11760578 TI - [Anal incontinence: echographic and manometric study]. AB - STUDY AIM: The goal of this study was to evaluate the clinical and functional consequences of anal sphincter echographic lesions in patients with fecal incontinence. PATIENTS AND METHOD: From January 1997 to April 2001, 100 patients with fecal incontinence (90 women, 10 men) were prospectively explored by transanal ultrasound and vectormanometry. Internal and external sphincter defects, as well as their extension, were analyzed with regard to their clinical and functional expressions (resting and squeeze anal sphincter pressures, anal sphincter asymmetry index). RESULTS: Among the 100 patients, 42 had no echographic lesions, 58 had a defect: 26 had an isolated defect (internal sphincter (n = 3), external sphincter (n = 23) and 32 had combined internal and external sphincter defects. Squeeze anal pressures were significantly lower in the group of patients with combined defects, compared to the group with isolated defect or without defect. Anal asymmetry index was higher in the group of patients with combined defects, compared to the other groups. There was a positive correlation between the radial extension of the defect and the importance of clinical complaints. CONCLUSION: Echographic anal sphincter lesions are frequent in fecal incontinence and are clinically and functionally significant. PMID- 11760579 TI - [Late intestinal fistula following implantation of parietal abdominal prostheses]. AB - STUDY AIM: The aim of this retrospective study was to describe an unusual complication of the nonabsorbable meshes used for repair of incisional hernia or inguinal hernia. PATIENTS AND METHODS: This study included eight observations of intestinal fistulas that occurred between 1 and 13 years after using Mersilene (Dacron) mesh for repair of an incisional hernia (7 cases) and an inguinal hernia (1 case). There were 6 men and 2 women (mean age: 58 years, range: 35-85 years) with an external intestinal fistula (n = 6) or an internal intestinal fistula (n = 2). All the patients required a reoperation for extraction of the mesh and treatment of the bowel injuries. RESULTS: There was one secondary death in a 85 years old woman in relation with a vascular complication after incomplete excision of the prosthesis. In five patients out of six, there was a recurrence of the incisional hernia. CONCLUSION: The intestinal fistulas associated with prosthetic repair of the abdominal wall are mostly observed with intraperitoneal mesh but this factor is not exclusive. Their frequency after repair of incisional or inguinal hernia with non absorbable mesh is estimated between 0.3 and 3.5%. The use of nonabsorbable mesh should be limited to the indications of strict necessity, without any septic context or emergency surgery. The contact of the mesh with the bowel should be formally avoided. PMID- 11760580 TI - [Growth and pubertal development following pediatric heart transplantation]. AB - STUDY AIM: Prospective study of growth and pubertal development following pediatric heart transplantation in 25 children. PATIENTS AND METHOD: Twenty-five children underwent orthotopic cardiac transplantation at Ste-Justine Hospital from July 1984 to August 1996. Systematic evaluation of anthropometric parameters (weight, height, bone age), hormonal profile (LH, FSH, testosterone, oestradiol, DHEAS), and pubertal development according to Marshall and Tanner were done yearly. RESULTS: Six patients had severe growth retardation at transplantation and only one patient was obese. All patients showed normal height increment following cardiac transplantation. Only 3 patients will not reach genetic target height. The 6 children suffering from congenital cardiomyopathy and showing severe growth delay before surgery did not show any significant catch up growth. Significant weight gain was observed during the first post-operative year (113 +/ 27% ideal body weight p = 0.0002) with evolution towards normal values at 2 years (100 +/- 18%). Thirteen patients were in the prepubertal stage at the time of transplant. Since then, one girl had her menarche at 11 years of age and 3 boys started their pubertal onset at 12 years old. The elevation of blood gonadotrophins during pubertal development correlated with progression of secondary sexual characteristics in both sexes. CONCLUSION: This pediatric population showed normal growth and normal onset and progression of puberty following cardiac transplantation. However, no catch-up growth was observed. The most important factor influencing attainment of maximal growth potential following heart transplantation was the degree of staturoponderal growth retardation at the time of surgery. PMID- 11760582 TI - [Hematemesis revealing chronic volvulus of a wandering spleen]. AB - A 23 years old woman was admitted on emergency for an upper digestive tract bleeding and endoscopy found gastric varices. CT scan revealed a splenomegaly, a twisted aspect of the splenic pedicle and varices in the gastrosplenic ligament. Arteriography showed a narrow splenic artery and varices in the gastrosplenic ligament. After a recurrent bleeding, splenectomy was performed. There was a chronic volvulus of a wandering spleen; the splenic venous flow was passing through the left gastroepiploic vein and a gastrosplenic vein. Chronic volvulus of a wandering spleen with gastric varices is an unfrequent pathology, diagnosed by imaging and requiring splenectomy. PMID- 11760581 TI - [The avian peripheral olfactory system: model for study of apoptosis and cellular regeneration]. AB - A reliable model, usable in vitro and in vivo, is necessary for analysis of processes engaged during cell death, regeneration and differentiation. The peripheral olfactory system is an attractive model for studying these processes through its dynamic neurogenesis that occurs continually throughout the lifetime. STUDY AIM: The aim of this study was the analysis of these processes on an animal model. MATERIAL AND METHODS: We performed axotomy of the nerve olfactory on young animals and chicken embryos E17. Then we infused IGF-I (insulin-like growth factor-I) in the lesioned site. Death, regeneration and differentiation of cells were studied by immunocytology. RESULTS: After hatching, the section of the olfactory nerve induced a rapid neuronal apoptosis at the 24th hour followed by a wave of mitosis 24 hours later. In prenatal stages, the response to the axotomy was rather similar to a dedifferentiation. In postnatal stages, the IGF-I infusion at the lesioned site had a triple function: survival of mature neurons, maintenance of differentiation and stimulation of mitosis. The neoneurogenesis, which occurred from neuronal stem cells would depend on the maturation and environment of the olfactory neurons protected from apoptosis by IGF-I. CONCLUSION: The avian olfactory epithelium is a good model for analysis of cell death, regeneration and differentiation. The capacity of these neuronal stem cells to dedifferentiate makes then more primitive than the pluripotent cells, closer to totipotent embryonic stem cells. PMID- 11760583 TI - [Solid cystic papillary tumor of the pancreas]. AB - Solid cystic papillary tumors of the pancreas are rare; they occur most commonly in young women. Despite their characteristic microscopic appearance, their immunophenotype is not specific. Their prognosis is excellent after complete surgical resection. The study aim was to report two cases in female patients who were 15 and 20 years old; the first tumor was discovered fortuitously and the second girl presented with abdominal pain and vomiting. Both tumors were encapsulated and located in the tail of the pancreas. The histological study showed the papillary architecture mixed with solid areas. Immunohistochemical staining was positive only for vimentin in one case and positive for cytokeratin, chromogranin, synaptophysin, neuron specific enolase, vimentin and protein S100 in the second case. PMID- 11760584 TI - [Black esophagus associated with hypothermia]. AB - The authors report a clinical case concerning a necrotizing esophagitis following severe hypothermic shock. They recall the usual aetiology of the "black esophagus", emphasize the importance of ischemia and the multispeciality management of this very unfrequent disease. PMID- 11760585 TI - [The anatomy collections of the Paris V University: their role in medical teaching for two centuries]. AB - The Museum of anatomy of the University Paris V exhibits a collection of ancient and high quality dissections and waxworks, very well preserved, which were used for teaching anatomy and have been classified historic monument since 1992. PMID- 11760586 TI - [Persistent dysphagia after Nissen procedure]. PMID- 11760587 TI - [Late mortality in severe acute pancreatitis]. PMID- 11760588 TI - [Effect of a tyrosine kinase inhibitors in a patient with a metastatic gastrointestinal stromal tumor]. PMID- 11760589 TI - [The impact factor or in publishing is it necessary to choose between The Orthopedic Surgery Review and the impact factor?]. PMID- 11760590 TI - Managing stable chronic obstructive pulmonary disease. AB - Over 26,000 people died of chronic obstructive pulmonary disease (COPD) in England and Wales in 1999. The disease is a common cause of consultations in primary care and accounts for as many as 1 in 8 medical admissions. Patients with stable COPD, the focus of this article, experience chronic symptoms such as breathlessness, cough, sputum production, wheeze and chest tightness, which worsen slowly over time. We do not deal here with the management of severe acute exacerbations, which are caused by an additional (often infective) process. PMID- 11760591 TI - Levonorgestrel intra-uterine system for menorrhagia. AB - In 1996, we concluded that the levonorgestrel intra-uterine system (levonorgestrel IUS; Mirena--Schering Health Care) was an effective contraceptive. The product is now also licensed as a treatment for "idiopathic menorrhagia", with the claim that it "may be particularly useful in women with idiopathic menorrhagia requiring (reversible) contraception". We assess the efficacy and safety of levonorgestrel IUS in the management of heavy menstrual bleeding. PMID- 11760592 TI - Medical devices that incorporate medicines. AB - There are now thousands of medical devices in use for the diagnosis, prevention, treatment or monitoring or disease or disability, and for contraception. Some of the devices used within the body also incorporate a medicine. What are the implications for the regulation of, and dissemination of information about, such products? PMID- 11760593 TI - [Mourning]. AB - A PAINFUL EXPERIENCE: Mourning characterizes the grief of a person who has lost a loved one forever. The bereavement that follows is natural and should not be medicated. Mourning is not a disease; it is one of the most painful facts of life. In fact, the more we are attached to someone, the more we will suffer his or her loss. This is unavoidable. The grief expressing our attachment is accompanied by immediate and intense regression with repeated need for consolation. For some people, it can be the means of coming to terms with their own mortality. THE STAGES OF MOURNING: There are several stages of mourning: the living person's ambivalence toward the deceased, the recollection corresponding to the progressive acceptance of the loss, which represents the first phase of the mourning process. During the healing phase, the mourner is gradually capable of recalling the good times during the life of the deceased and then progressively of evacuating the souvenirs and start living and opening up to others again. COMPLICATED MOURNING: Mourning may be passionate and characterized by the refusal to integrate the loss, or delayed, with an apparent lack of grief and sorrow. Chronic depression is a sort of greater degree of severity compared with delayed mourning. A denial mechanism installs: the loved one is not dead and will return. A split in personality can be observed: part of the person will integrate the reality; the other will retreat from it. In this case, recollection will not lead to integration of the loss. Somatization disorders or organic problems can be observed and more rarely grief melancholia, mania, hysteria or obsessional grief. These are the domain of the specialist. GENERAL PRINCIPLES FOR THE PHYSICIAN: Reality is always preferable to imagination. Listening to the patient must precede any medication. In severe cases of grief, sedative antidepressors are preferable and the co-prescription of anxiolytics, particularly benzodiazepines should be avoided. One should not hesitate to seek advice from a specialist. PMID- 11760594 TI - [Causes of fever in adults infected by HIV-1. Ambulatory follow-up in the ANRS 059 trial in Abidjan, Ivory Coast]. AB - OBJECTIVE: Describe the causes of fever in HIV-1 infected adults in Abidjan, Ivory Coast. METHODS: Exhaustive analysis of all the morbid episodes with raise in temperature to above 37.5 degrees C in patients followed-up prospectively, within the framework of the ANRS 059 study from April 1996 to March 1998. RESULTS: One hundred and four patients presented 269 episodes of fever. At the start of these episodes, the mean CD4 count was of 311/mm3, fever had lasted a mean of 3.4 days and mean body temperature was 38.7 degrees C. The 269 episodes lead to 288 diagnoses: 152 specific etiologic diagnoses and 136 non-specific syndrome diagnoses. Community bacterial infections represented 55% of the specific diagnoses, followed by malaria (16%) and tuberculosis (12%). The mean CD4 count during the bacterial episodes was 208/mm3, in malaria 384/mm3 and in tuberculosis 245/mm3. Non-typhi salmonella, pneumococci and Escherischia coli represented 37%, 32%, and 15% respectively of the bacteria isolated. The mean duration between the first and last day of fever was 8.4 days. This time lapse was superior or equal to 30 days in 22 episodes (8%), 50% of which were mycobacterioses (36% tuberculosis and 14% atypic mycobacterioses). Nineteen episodes (7%) lead to death within a mean delay of 58 days. The first cause of death was atypic mycobacteriosis (26%). Death was significantly associated with a CD4 count < 200/mm3 and to prolongation of fever for more than 30 days. CONCLUSION: Other than the frequently described role of tuberculosis in HIV morbidity in sub-Saharian Africa, the role of bacterial diseases, responsible for early death, potentially severe, but curable should be underlined. The diffusion of antibiotic treatment algorithms adapted to the principle clinical syndromes encountered, might improve the treatment of adults infected by HIV consulting in sub-Saharian Africa. PMID- 11760595 TI - [Successful treatment of gastroesophageal reflux with anterior partial fundoplication under celioscopy]. AB - OBJECTIVE: To study the interest of partial fundoplication under laparoscopy, not only in terms of efficacy but also in the low rate of complications. METHODS: The study included all patients having undergone coelioscopic surgery for gastroesophageal reflux from January 1995 to February. A ventral semi-valve was created in all patients. Complications during surgery and post-surgical follow-up immediately after, six weeks later and then at distance were analyzed. RESULTS: The mean duration of surgery was 81 minutes (40-170 min.) and mean hospital stay 6.2 days (2-12 days). Twelve conversions were observed (9.6%) and post-surgical morbidity was of 9.7% after coelioscopy. At 6 weeks, 72 patients (63.7%) were satisfied with the operation, 13 patients (11.5%) complained of dysphagia and 5 (4.4%) of bloating. At distance, after a mean of 3.2 years (0.5-5.5 years), 72 patients (73%) were totally satisfied; 4 presented recurrent reflux (4.1%) and 3 patients (3.1%) complained of dysphagia. CONCLUSION: The results of laparoscopic surgery for gastroesophageal reflux with creation of a ventral semi-valve are encouraging. Pre-existing symptomatology is eradicated and post-surgical complications are clearly decreased. PMID- 11760596 TI - [Congenital syphilis still exists]. AB - INTRODUCTION: Even today screening for congenital syphilis must be performed and confirmed by appropriate serological tests and bacteriological samples. OBSERVATION: A newborn presented with an apparently materno-fetal or viral fetal disease. It was in fact congenital syphilis. The mother exhibited no risk factors for syphilis. Systematic serological search for syphilis was negative in the mother at 11 weeks of amenorrhea. No signs of primary or secondary syphilis had been observed during pregnancy. At twenty-nine weeks of amenorrhea, the mother presented a menace of preterm delivery and no tocolysis at 31 weeks. Examination of the newborn revealed clinical signs of aterno-fetal infection, without specificorientation. Initial bacteriological and virological analyses were negative. Screening for specific Treponema pallidum M-type immunoglobulines (IgM) on the 9th day of life, confirmed the diagnosis of congenital syphilis. COMMENTS: Diagnosis of congenital syphilis must not be eliminated during early serological screening: clinical suspicion must lead to further anamnesis again and serological tests both in the newborn and the mother. PMID- 11760597 TI - [Bacterial pneumopathy facilitated by diazepam in acute poisoning with chloroquine]. PMID- 11760598 TI - [Glaucoma disclosing a small-cell bronchial carcinoma]. PMID- 11760599 TI - [Aortoduodenal fistula on aortic prosthesis]. PMID- 11760600 TI - [Pendred's syndrome. Current features]. AB - Introduction Pendred's syndrome is a recessive autosomal disease, traditionally defined as the association of deaf-mutism, goiter and dysfunctional iodide organization revealed by the perchlorate discharge test. It represents 4 to 10% of the causes of congenital hypoacusis. Although described more than a 100 years ago, the association of thyroid and cochleo-vestibular damage remained unclear for many years. Genetic abnormalities Progress in molecular biology has revealed that the disease is related to alterations in the PDS gene situated on chromosome 7. The PDS gene is responsible for the production of pendrine, protein involved in anion (l-, Cl-) transportation, notably in the apical pole of the thyreocyte and the cochlear duct, where the endolympha is produced. Practical implications The truncation of pendrine related to the genetic alterations be responsible for the morpho-functional alterations in the cochlear apparatus and the thyroid. In this perspective, Pendred's syndrome would appear as a genetic disorder in anion transportation. PMID- 11760601 TI - [Serotonin syndrome. Which treatment and when?]. AB - A TOXIC REACTION: Prevalence of the serotonin syndrome is increasing and can be fatal. The physiopathological hypothesis is principally supported by excess stimulation of the central (5HT1a) serotonin receptors. There are various serotonin drugs and associations implied. Monoamine oxidase inhibitors appear to be the major culprits. RECENTLY REVISED CLINICAL DIAGNOSIS FACTORS: The classical triad of neuropsychiatric, neuromuscular and neurovegetative symptoms, described in 1991 by Sternbach, has recently been modified. The syndrome is however protein like and differential diagnosis remains the neuroleptic malignant syndrome. FIRST LINE THERAPEUTIC MEASURES: Prevention of the syndrome and its early discovery are essential. Withdrawal of the imputable drugs often resolves the symptoms within 24 hours. Symptomatic and supportive care remains the pillar to treatment. ORIENTATION TOWARDS SPECIFIC TREATMENTS: Several non-selective anti-serotonin treatments have been tested without much success. In the absence of prospective studies, current therapeutic strategies rely on case reports demonstrating the relative efficacy of cyproheptadine and chlorpromazine. The proposed treatment, as soon as severe or persisting symptoms are observed, is administration of 8 to 30 mg cyproheptadine per os, and in the case of failure or contraindication, followed by 50 to 100 mg of intramuscular chlorpromazine, renewed when necessary. PMID- 11760602 TI - [Systemic markers of inflammation after coronary angioplasty]. AB - THE RISK OF RESTENOSIS: Coronary angioplasty is an effective treatment of stable and instable coronary disease and its principle limitation, despite technical progress, remains restenosis. In instable angina, the physiopathologic and prognostic role of inflammation proteins is well documented. THE ROLE OF THE C REACTIVE PROTEIN (CRP): Is a validated risk factor for patients presenting with heart failure, whether instable or stable angina and in the general population. This risk factor is distinct from tobacco abuse, hypercholesterolemia or diabetes. In all the series studied to date, the frequency of restenosis following coronary angioplasty increases when CRP values are high prior to surgery and continue to rise up to the 48th or 72nd hour. PERSPECTIVES: New therapeutic measures widen the possibilities of mechanical strategies (angioplasty with or without stent) and treatment of inflammatory mechanisms in the atheromatous plaques (statines, brachytherapy or "covered" stents). PMID- 11760603 TI - [Perinatal pertussis: from mother to child]. AB - Two infants, a girl, aged four weeks, and a boy, aged three weeks, came to our attention with poor feeding and weight loss. Later the typical cough of pertussis appeared. Serological testing confirmed that both patients' mothers had recently had pertussis. One mother suffered from severe and typical coughing periods even throughout labour. Despite the vaccination program in the Netherlands, each year new-born infants with pertussis require hospitalisation. Pertussis during the neonatal period is seldom described. Adults can suffer from pertussis, even when they have been vaccinated in childhood. They then become contagious for unvaccinated infants. Pertussis during the neonatal period is an insidious disease with sometimes severe complications. If pertussis is suspected in mothers with new-born infants or pregnant women towards the end of the pregnancy, they should be treated with antibiotics to prevent pertussis in the new-born infant. PMID- 11760604 TI - [Total mesorectal excision and preoperative radiotherapy in patients with rectal carcinoma: good preliminary results]. AB - The value of a short course of radiotherapy prior to total mesorectal excision was studied in patients with resectable rectal cancer. The new surgical technique of total mesorectal excision was introduced under appropriate supervision and gave favourable treatment results. The incidence of local recurrence was markedly reduced by preoperative radiotherapy. Long term results should give greater insight into potential improvements in survival rates and any late side effects which may arise as a result of the radiation schedule. PMID- 11760605 TI - [Follow-up after oncological surgery]. AB - After an operative and adjuvant treatment of solid tumours there are a number of reasons for follow-up: treatment of the functional and psychological results of the therapy, quality control with respect to the treatment, screening for metachronous tumours, reassuring the patient, and the detection of asymptomatic recurrences. Most follow-up schedules are based on the probability of a recurrence and not on the effectiveness of possible interventions. Negative effects are false positive test results, morbidity and even mortality due to a new intervention, and the knowledge that there is a recurrence for which in the absence of complaints no effective treatment is possible. In the ideal situation every patient should have a personal monitoring schedule based on the aforementioned considerations whilst taking into account comorbidity and the patient's wishes. This documented agreement should state the frequency of the follow-up visits, the type of examination and the person responsible for carrying out the monitoring. PMID- 11760606 TI - [Clinical thinking and decision making in practice. 4 times ERCP, 6 times ultrasonography of the upper abdomen and 3 CT-scans for a woman with recurrent fever and bacteremia]. AB - A 42-year-old woman was hospitalised due to recurrent fever (40 degrees C) and bacteraemia. A physical examination revealed no abnormalities. Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Enterococci were found in blood cultures. Laboratory results revealed liver enzyme levels which were only slightly elevated. An X-ray investigation, ERCPs, CT scans, ultrasounds, a leucocyte scintigram and a gallium scan, all revealed no abnormalities. Due to the results from the blood cultures it was thought that the bile duct system or the digestive tract were the focus of infection. Therefore a liver biopsy was carried out for the purpose of making a diagnosis. The patient was diagnosed as having ductal plate malformation, a microscopic congenital cystic dilatation of the bile ducts. The prognosis is poor and the treatment consists of lifelong antibiotics. PMID- 11760607 TI - [Diagnostic image (65). Unintentional biopsies of the gastric mucosa, obtained by withdrawal of a stomach tube]. AB - Three biopsies from the mucosa of the stomach were taken, unintentionally, in a 24-year-old man, by withdrawing a stomach tube that was used for lavage after an autointoxication. PMID- 11760608 TI - [Deep venous thrombosis as a complication of congenital absence of vena cava inferior]. AB - A 19-year-old man was admitted with fever, haematuria, general malaise, pain on the left side of the pelvis and a full feeling in the left lower abdominal quadrant of the abdomen. His history mentioned a varices operation. During admission he developed an acute abdomen and deep vein thrombosis in both legs. CT of the abdomen showed a pathologic mass and absence of the vena cava inferior. Laparotomy revealed extensive thrombosis in widened veins. Clinical improvement occurred following adequate thrombolysis. Congenital absence of the vena cava inferior results from aberrant development during organogenesis. Patients are typically asymptomatic, but may present with venous insufficiency at a young age and deep vein thrombosis. Absence of the vena cava inferior can be accompanied by other congenital abnormalities such as dextrocardia and congenital heart diseases. Diagnosis is made using CT or MRI. Treatment consists of lifelong anticoagulant therapy and, if necessary, surgery. PMID- 11760609 TI - [Traumatic atlanto-occipital dislocation with minimal neurologic deficits]. AB - A 21-year-old woman presented with mild neck pain following a scooter accident. Conventional cervical radiographs showed a lateralisation of the dens axis to the left in relation to the foramen magnum. A subsequent CT with a multiplanar reconstruction revealed an atlanto-occipital dislocation that was repositioned under fluoroscopic control. The patient had an uneventful recovery; a mild loss of strength in the left arm remained. The atlanto-occipital dislocation without neurological deficit is rare. PMID- 11760610 TI - [Optimal medical care for children with Down syndrome and their parents]. PMID- 11760611 TI - [Treatment of rheumatoid arthritis by inhibition of tumor necrosis factor with infliximab or etanercept]. PMID- 11760612 TI - The relevance of lowered personal control for patients who have stoma surgery to treat cancer. AB - OBJECTIVES: The objective of this study was to explore the experience of patients who had stoma surgery to treat cancer in order to explicate why problems associated with stoma surgery are not decreasing despite technical improvements in stoma care. DESIGN: A longitudinal design was used in order to capture the process of preparing for surgery and dealing with its aftermath. Participants were interviewed using a semi-structured protocol on three occasions; 1-2 weeks before surgery (eight participants), 1-2 weeks after surgery (seven participants), and 3 months after surgery (four participants). METHOD: Transcripts were analysed guided by the procedures of grounded theory. This involved developing categories from the data and linking them together to form a conceptual understanding of our participants' experience. RESULTS: Lowered personal control was the most important concept to emerge from the analysis. We identified perceived causes of lowered control, its mitigating factors, the strategies used to manage this experience and the consequences of these processes. CONCLUSIONS: We make three recommendations based on the conclusion that improvements could be implemented in the psychological aspects of stoma care and, in particular, the enabling of patient perceived self-efficacy. First, improvements could be made in doctor-patient communication with doctors becoming more aware of their psychological impact on patients. Second, specialist stoma care nurses could be trained to recognize patients with dysfunctional self efficacy beliefs and/or delayed psychological adaptation. Finally, we identify a need for more prolonged practical and emotional support for at least some stoma out-patients. PMID- 11760613 TI - Affective reactions to auditory hallucinations in psychotic, evangelical and control groups. AB - OBJECTIVES: Building on recent work on the similarities and differences in delusional ideation between psychotic and religious populations (Peters, Day, McKenna, & Orbach, 1999), the experiences of auditory hallucinations in psychotic, evangelical and control groups were examined in this study. METHOD: The incidence and subjective experiences of hearing voices were assessed using questionnaire methods in psychotic out-patients, evangelical Christians and controls (non-psychotic, non-evangelical). RESULTS: Incidence of auditory hallucinations differed significantly across the three groups with psychotics showing the highest levels and controls the lowest levels. The experiences of the evangelical group were significantly more positive than those of the control group, which in turn were significantly more positive than those of the psychotic group. The most recent experience of hearing voices was rated more positively than the first experience by the psychotic and religious groups but not by the control group. These findings were much stronger for affective reactions to the experiences than for perceptions of the voices. CONCLUSION: These results provide only partial support for the findings of Peters et al. (1999) on differences in delusional ideation and possible reasons for this are discussed. The findings for religious and psychotic individuals are discussed further in terms of interpretational and coping mechanisms. PMID- 11760614 TI - An investigation of models of illness in carers of schizophrenia patients using the Illness Perception Questionnaire. AB - BACKGROUND: Although carers' reactions to schizophrenic illness in a close family member may have important implications for the patient and for themselves, little is known of factors that influence the way carers respond. In the area of physical health problems, people's models of their illness or illness representations have been found to be related to the ways they react and cope with their illness. This study examines the use of a modified form of the Illness Perception Questionnaire (IPQ) to investigate illness models in a sample of carers of schizophrenia patients. METHODS: Forty-seven carers participated. The psychometric properties of the modified IPQ were examined, and a number of carer and patient outcomes were investigated in relation to carer scores on the illness identity, consequences, control-cure and timeline subscales of the modified IPQ. These outcomes included measures of carer distress and burden, expressed emotion dimensions, and patient functioning. RESULTS: The modified IPQ was found to be a reliable measure of carers' perceptions of schizophrenia. Carer functioning, the patient-carer relationship and patient illness characteristics were associated with different dimensions of illness perceptions. CONCLUSIONS: The findings support the proposal that carer cognitive representations of the illness may have important implications for both carer and patient outcomes in schizophrenia. PMID- 11760615 TI - The utility of dimensional and categorical approaches to understanding dissociation in the eating disorders. AB - OBJECTIVE: The present study compared levels of dissociation across groups of eating-disordered women, investigating the utility of dimensional and categorical measures of dissociation in understanding diagnoses and behaviours in the eating disorders. METHODS: The Dissociative Experiences Scale (DES-II) was completed by 170 eating-disordered women (drawn from out-patient assessment clinics) and 203 nonclinical women. The clinical group also supplied information regarding eating behaviours and related features (alcohol abuse, reported history of sexual abuse). The DES-II and a subset of its items (DES-Taxon) were used as dimensional and categorical discriminators of the groups and of the presence/absence of specific features and symptoms. RESULTS: When treated as dimensional measures, the DES-II and DES-Taxon had similar levels of clinical utility (particularly discriminating the binge-purge anorexics from the other clinical groups). However, the DES-Taxon was a superior categorical measure, discriminating groups more clearly and predicting the presence of many symptoms and features much more powerfully. CONCLUSIONS: The DES-Taxon is a potentially valuable self-report measure for indicating the level and presence of dissociative psychopathology in the eating disorders. As well as being convenient to administer and score, it has the clinical and research value of indicating those patients in whom treatment might need to include addressing pathological dissociation. PMID- 11760616 TI - Prevention of anxiety symptoms in primary school children: preliminary results from a universal school-based trial. AB - Preliminary data are presented on the effectiveness of a universal school-based intervention for the prevention of anxiety symptoms in primary school children. A sample of 489 children (aged 10-12 years) were assigned to one of three intervention conditions: a psychologist-led preventive intervention, a teacher led preventive intervention, or a usual care (standard curriculum) with monitoring condition. The intervention offered was the Friends for Children programme, a 12-session cognitive-behavioural intervention, originally based upon Kendall's (1994) Coping Cat programme. Participants in both intervention conditions reported fewer symptoms of anxiety at post-intervention than participants in the usual care condition. These preliminary results suggest that universal programmes for childhood anxiety are promising intervention strategies that can be successfully delivered to a school-based population and integrated into the classroom curriculum. PMID- 11760618 TI - Normative data for the HADS from a large non-clinical sample. AB - OBJECTIVES: To provide normative data for the Hospital Anxiety Depression Scale (HADS). DESIGN: Repeated measures and correlational. METHODS: The HADS was administered to a non-clinical sample, broadly representative of the general adult UK population (N = 1792) in terms of the distributions of age, gender and occupational status. Correlational analysis was used to determine the influence of demographic variables on HADS scores. RESULTS: Demographic variables had only very modest influences on HADS scores. The reliability of the HADS is acceptable; the Anxiety and Depression scales are moderately correlated (.53). Tables to convert raw scores to percentiles are presented for females and males. CONCLUSIONS: The present normative data allow clinicians to assess the rarity of a given HADS score, and thus provide a useful supplement to existing cut-off scores. PMID- 11760617 TI - Predicting onset of depression: the Vulnerability to Depression Questionnaire. AB - OBJECTIVES: The development of a self-report questionnaire capable of assessing cognitive and interpersonal vulnerability factors for clinical depression is described. The Vulnerability to Depression Questionnaire (VDQ) was developed to provide a brief, economical alternative to the Self-Evaluation and Social Support interview (SESS; O'Connor & Brown, 1984), assessing negative evaluation of self, negative interaction with partner or child and lack of a support figure. DESIGN: The VDQ was tested in a prospective study of community-based women who were contacted on three occasions over the course of approximately 1 year, to: (i) compare the VDQ's capacity to categorize vulnerability compared with the SESS interview, and (ii) to test the VDQ's prediction of onset of clinical depression during the follow-up. METHOD: Selected nondepressed respondents completed the VDQ and were interviewed to determine their vulnerability using the SESS. They were re-interviewed on two further occasions during the follow-up period, and the VDQ was also re-administered at the time of first follow-up. Onset of clinical depression during the follow-up was assessed by interview at each contact. RESULTS: Comparison of VDQ and SESS interview classification of participants' vulnerability at first contact indicated that the questionnaire had good sensitivity and specificity. Test-retest scores for the VDQ indicated satisfactory levels of reliability. VDQ scores also predicted onset of clinical depression in the follow-up period. CONCLUSIONS: Results suggest that the VDQ is an economical and effective means of screening large populations for the purposes of risk assessment, to aid future research into clinical depression and to facilitate the implementation of intervention strategies. PMID- 11760619 TI - Strengthening relationships for a successful nurse directed center within an academic setting. AB - This article focuses on the evolvement of a nurse-directed student health center within an academic setting. The advantages of having a student health center located under academic affairs versus the traditional model of being placed under student affairs is discusses. How this organizational arrangement can be used to develop and strengthen relationships, as well as promote collaboration among various disciplines within the college is discussed. Such an arrangement can provide resources, student practicum experiences on campus as well as strengthen and develop relationships within the surrounding community. These strategies can be used to create a forum for discussion of various strategies which will assist in establishing a vision, overcoming obstacles, expanding the center's scope of services as well as provide mentoring opportunities for student nurses and faculty. PMID- 11760620 TI - Community health indicators predicting adolescent academic achievement. AB - Throughout the literature investigating adolescent academic achievement, little or no attention has been focused on indicators of community health as factors that share variance with academic achievement. The purpose of this study was to conduct exploratory analyses using indicators of community health to investigate adolescent academic achievement. This study employed hierarchical linear multiple regression to explain variations in adolescent academic achievement as measured by standardized tests for two different school years. The unit of analyses was the school district with the standardized test results of 8th grade students as academic achievement. The first model of the school district for school year 1997 98 accounted for almost 58% of the variance in adolescent academic achievement. This model was replicated on a different school year and it accounted for almost 63% of the variance in adolescent academic achievement. These strong models hold great promise for future investigations of adolescent academic achievement using indicators of community health and other community contextual variables. PMID- 11760621 TI - Clinical decisions using the National Triage Scale: how important is postgraduate education? AB - Triage is the formal nursing assessment of all patients who present to an Emergency Department (ED). The National Triage Scale (NTS) is used in most Australian EDs. Triage decision making involves the allocation of every patients presenting to an ED to one of the five NTS categories. The NTS directly relates a triage category to illness or injury severity and need for emergency care. Triage nurses' decisions not only have the potential to impact on the health outcomes of ED patients, they are also used, in part, to evaluate ED performance and allocate components of ED funding. This study was a correlational study that used survey methods. Triage decisions were classified as 'expected triage', 'overtriage' or 'undertriage' decisions. Participant's qualifications were allocated to five categories: 'nil'; 'emergency nursing'; 'critical care nursing'; 'midwifery'; and 'tertiary' qualifications. There was no correlation between triage decisions and length of experience in emergency nursing or triage. 'Expected triage' decisions were more common when the predicted triage category was Category 3 (P < 0.001) and 'overtriage' decisions were less common when the predicted triage category was Category 2 (P < 0.0010). The frequency of 'undertriage' decisions decreased significantly when the predicted triage category was Category 3 (P < 0.001) or Category 4 (P < 0.001). There was no correlation between triage decisions and qualifications in the 'nil', 'emergency nursing' or 'critical care nursing' categories. A midwifery qualification demonstrated a positive correlation with 'expected triage' decisions (P = 0.048) and a negative correlation with 'undertriage' decisions (P = 0.012). There was also a positive correlation between a tertiary qualification and 'expected triage' decisions (P = 0.012). PMID- 11760622 TI - Organ donation in A&E: the legal and ethical implications for the A&E nurse. AB - In the U.K. the requirement for organs grows daily and sadly many people will die before an organ for transplant becomes available. In an effort to improve the supply of organs some clinicians are now looking to the A&E department to identify potential organ donors occurring as a result of a sudden death in the department. Many people take the view that hundreds of potential organs are wasted every year, as a result of the A&E departments' failure to notify the organ transplant co-ordinator of a potential donor in sufficient time to seek consent from the relatives. This paper will explore the legal and ethical principles which underpin the current organ donations system in the U.K., and explore the rationale for the reluctance of the majority of A&E departments to utilise this option. Some possible solutions to the conflicts which this option presents to the A&E nurse will be proposed. PMID- 11760623 TI - The extent and nature of emergency nurse practitioner services in Scotland. AB - Emergency Nurse Practitioners (ENPs) are being used in an increasing proportion of A&E departments across England and Wales. This paper reports the findings of a postal survey sent to all (94) A&E departments in Scotland including the smaller GP run units. The aim of the study was to document the extent and nature of ENP services in Scotland. Nurses were found to be practising as ENPs in 47% of Scottish A&E departments. The majority (70%) of nurses practising as ENPs had been educated for the role on courses for ENPs. Nurses working as ENPs were being paid at all grades ranging from the lowest grade for a staff nurse (D-grade) through to H-grade. ENPs are practising in all types of A&E department. Most ENPs have been formally trained for the role, however huge variation exists in educational preparation and in remuneration for this expanded nursing role. PMID- 11760624 TI - Who is to blame? PMID- 11760626 TI - Writing academic papers: the Clinical Effectiveness in Nursing experience. PMID- 11760625 TI - How do ambulance personnel experience work at a disaster site? AB - Working at a major accident site is a complex matter where knowledge from various fields must be put into practice. In addition, the different situations at emergency and disaster sites place a variety of demands on personnel, equipment and organization. The aim of the present study is to investigate how the ambulance personnel perceived their own action and the functioning of the whole emergency organization at a major accident site (large discotheque fire) in 1998. Working from a list obtained from the fire department, a questionnaire with 57 questions was sent to the personnel (n = 36) who had participated at the accident site either as ambulance crew members or as members of a medical team sent out from the hospital. The response rate was 80 per cent. Despite the extreme situation, most of the ambulance personnel involved were satisfied with their own preparedness as well as the medical and nursing care performed at the site. Those who where not satisfied reported that the main reason for dissatisfaction was lack of time to calm and comfort people who were not injured or had only minor injuries. The need of more medical support for the medical team members at the site was also emphasized with regard to the care of the severely injured. The ambulance service crews from the suburbs, in comparison with the local city rescue service, were, in general, less satisfied with the co-operation from other rescue units. PMID- 11760627 TI - Dilemma. Incompetence by colleagues. PMID- 11760628 TI - Violence in A&E departments: a systematic review of the literature. AB - Violence against A&E staff is increasing, and national initiatives have been implemented to counter the threat to staff. The aim of this paper is to determine the risks to staff of working in A&E and to determine methods of risk-reduction, using searches of literature and web-based resources. There is also critical appraisal of the data therein. PMID- 11760629 TI - The Boston experience. AB - In April 2000, three nurses from Chesterfield (UK) were successful in an application for a travel scholarship. The scholarship was to examine emergency nurse practitioner (ENP) schemes in Boston USA after completion of my dissertation based on the same subject, in the course of which the broad span of ENP work had become obvious to me. Leading up to the trip overseas, we discussed specific objectives we hoped to meet but we did not expect the range of experiences we were exposed to within this busy city. It became apparent while in Boston, that we should avoid becoming too focused otherwise we might miss valuable information or experiences which would benefit practice back in the UK. Six of the most striking issues, which impressed all three of us, are covered in this paper. These are then reflected back to UK practice in an attempt to discover whether these experiences can benefit our own profession. Subjects covered include: student training; ENP training and role parameters; physician assistants; primary care and the effect of information technology on the emergency care culture. PMID- 11760630 TI - Management of alcohol misuse in Scotland: the role of A&E nurses. AB - Despite national targets to reduce excessive drinking in Scotland, rates have increased dramatically since the mid-eighties. The role of Accident and Emergency (A&E) departments in the management of alcohol misuse is much debated. This postal survey was conducted with senior medical and nursing staff in A&E departments and minor injury units throughout Scotland to examine the prevalence of alcohol-related attendances and staff's attitudes towards identifying and responding to alcohol-related attendances. A 57% response rate was achieved, representing 87% of all A&E institutions in Scotland (n = 84). The results reveal an estimated 1 in 7 attendances in A&E in Scotland are alcohol-related, and 1 in 5 of these result in admission. However, over two-fifths of departments do not routinely screen for, or keep records of, patients who attend with alcohol problems. Intervention is normally limited to a brief dialogue and referral to the patient's GP. Despite considerable barriers, A&E nursing staff express a willingness to assume a preventive role, but acknowledge lack of appropriate training and sources of support. It is concluded that there is scope for developing identification and brief intervention services within A&E. However, such developments are dependent upon alcohol issues assuming a higher priority among senior A&E staff. PMID- 11760632 TI - What are the legal or malpractice issues faced by case managers? PMID- 11760631 TI - Cultivating effectiveness in your organization. AB - To be truly effective, the occupational and environmental health nurse must possess skills as both a manager and a leader. Effective management results in programs and projects that are likely to be successful, achieve established goals, and meet expectations of the intended recipients. Effective leadership results in individuals who feel valued for their opinions, empowered to act independently, and accountable for setting and achieving personal goals. When these individuals come together to form teams, they create an organization in which the group benefits from the commitment and mutual desire to work toward a shared mission and vision. The nursing process provides an excellent framework for the occupational and environmental health nurse to approach the tasks associated with leading and managing in a rapidly changing, challenging environment. Techniques to be employed are those acquired in formal management training programs and those passed down from experienced mentors. It is incumbent on all occupational and environmental health nurse managers to perfect and use leadership and management skills to positively contribute to organizational effectiveness and, ultimately, employee health and well being. PMID- 11760633 TI - Case management services for work related upper extremity disorders. Integrating workplace accommodation and problem solving. AB - A case manager's ability to obtain worksite accommodations and engage workers in active problem solving may improve health and return to work outcomes for clients with work related upper extremity disorders (WRUEDs). This study examines the feasibility of a 2 day training seminar to help nurse case managers identify ergonomic risk factors, provide accommodation, and conduct problem solving skills training with workers' compensation claimants recovering from WRUEDs. Eight procedural steps to this case management approach were identified, translated into a training workshop format, and conveyed to 65 randomly selected case managers. Results indicate moderate to high self ratings of confidence to perform ergonomic assessments (mean = 7.5 of 10) and to provide problem solving skills training (mean = 7.2 of 10) after the seminar. This training format was suitable to experienced case managers and generated a moderate to high level of confidence to use this case management approach. PMID- 11760634 TI - Stress and coping. A model for the workplace. AB - Stress, both positive and negative, is a part of personal and work life. Some stressors in the work environment are so extreme they cause strain to all employees. Such conditions require immediate response by employers to change the work environment. However, understanding most workplace stress requires an approach examining the fit between the individual and the work. Only by holistically examining the relationships between the worker's characteristics and the job's characteristics can successful intervention strategies be planned and implemented. Once occupational and environmental health nurses have completed an occupational stress assessment they can plan primary, secondary, and tertiary interventions to meet the specific needs of the employees and the organization. PMID- 11760635 TI - Turning workplace anger and anxiety into peak performance. Strategies for enhancing employee health and productivity. AB - Traditional corporate approaches toward anger and anxiety in the workplace have ignored or exacerbated the problem. Human emotions are not only essential for job performance, they are a free resource that can be harnessed in ethical ways to enhance job productivity. Most of the causes and costs of workplace anger and anxiety can be prevented. In an ideal workplace, employees are internally motivated and self regulating because they are hired with care, placed in jobs serving them as well as the company, and supported with the required resources to accomplish their jobs. When companies treat employees with dignity and make efforts to empower them, employee self confidence and performance grows. Occupational and environmental health nurses are in positions to alter dysfunctional aspects of corporate culture while simultaneously working with individual employees who are angry or anxious. Successful companies are those that nurture their workers while achieving their mission. They treat employees with dignity and respect while challenging them to reach their full potential. PMID- 11760636 TI - Disapproving OSHA's ergonomic standard. PMID- 11760637 TI - Travel health. PMID- 11760638 TI - Confidentiality and genetic information. PMID- 11760639 TI - Legal update--application of the ADA to contingent workers. PMID- 11760640 TI - A mobile mammography program in the workplace. Successful program. AB - United States companies recognize health care costs are rising and the prevention, early detection, and treatment of disease can help with cost control. Onsite mobile mammography can provide a convenient, effective, and time saving service for employees. Establishing a mobile mammography program requires some planning, but is relatively easy to administer and maintain. PMID- 11760641 TI - Effective ergonomic teaching for positive client outcomes. Implications for practice. AB - Teaching and intervention are integral aspects of professional nursing practice. Numerous publications encourage the use of specific teaching intervention techniques, but few are validated by studies conducted to assess actual teaching behaviors of nurses who administer successful teaching intervention programs. This is a case study of one occupational health nurse who administers a highly effective ergonomic program for employees in a large urban hospital. Themes identified during observation of nurse and client interactions include mindfulness on the part of the nurse, respect for client autonomy, nurse effort, nurse accessibility, and professional distance. A consistent teaching process identified during observation consists of six steps: inquiry, invitation, assessment, synthesis, validation, and progression. This six step process is embedded within identified themes. Teaching and intervention methods identified in the study are a synthesis of caring behaviors and nursing process. This integrated method is entitled "Effective Teaching Through Unified Process and Caring Interpersonal Behavior." It may represent a valid teaching and intervention method supporting compliance and positive client outcome when interacting with clients requiring ergonomic teaching and intervention. PMID- 11760642 TI - Agricultural health nurses. Job analysis of functions and competencies. AB - Agricultural health nurses address the health and safety issues of farmers, agricultural workers, and farm families. This nurse role incorporates both public health and occupational health nurse specialty practice. The purpose of this study was to describe agricultural health nurse job functions and competencies used in providing services to agricultural populations. A two round modified Delphi technique was used to attain a consensus among participants related to agricultural health nurse functions and competencies. In Round I, a mailed survey assessing demographic characteristics, and job functions and competencies was sent to an identified list of 61 nurses. A second mailed survey, with categorized job function and competency responses elicited through Round I, was sent to the 32 Round I respondents to assess the importance of the job functions and competencies and the frequency of performing each job function. Twenty four Round II surveys were returned. Job functions rated highest were: Serve as a liaison for the agricultural, health and medical, and nonfarm communities. Promote agricultural health and safety issues through the media. Implement educational courses for various groups. Conduct follow up assessment of injury, illness, or disease occurring as a result of an agricultural exposure. Function as a resource for information to victims of agricultural injury and illness and their families. The competencies of greatest importance were interpersonal communication skills, knowledge of injury prevention principles and measures, ability to recognize potential hazards within the work and home environment, and demonstrate a strong sense of self. This study adds to the body of knowledge needed to define the agricultural health nurse role. PMID- 11760644 TI - Avoid identity theft in the workplace. PMID- 11760643 TI - Health assessment for the occupational and environmental health nurse. Skills update. AB - The assessment and management of clinical problems of employees related to occupational and non-occupational health are key components within the scope of the occupational and environmental health nurse practice. Employees present with various physical or psychosocial problems. The occupational and environmental health nurse must be equipped to make appropriate assessments and decisions related to the employees' care and referral. Use of a structured health assessment tool provides a systematic approach to identification of health needs given the stated goals of maintaining employee health and securing a safe work setting. PMID- 11760645 TI - [Clinical symptoms, diagnosis and treatment of focal dystonias]. AB - Focal dystonias are relatively rare and significantly disabling disorders. These include cervical dystonia, blepharospasm and hemifacial spasm. The spasmodic torticollis consists of tonic posturing of the head away from its neutral position or twisting of the cervical muscles. The blepharospasm is an abnormal blinking, eyelid tic or twitch resulting from any cause. The hemifacial spasm is an involuntary unilateral twitching of the facial muscle. Patients affected by focal dystonias are predominantly females, and many times psychical stress can be revealed. The pathogenesis may involve dysfunction of the basal ganglia and brain stem although the exact mechanism remains to be elucidated. The patients need to be diagnosed and treated in centers specialized in movement disorders. Although many drug treatments can be beneficial, the most effective treatment is the local Botulinum toxin injection into the affected muscles. This neurotoxin produces temporary neuromuscular blockade, which reveals the symptoms and pain. The effect of the toxin is temporary and, therefore, the injection needs to be repeated every 6-12 weeks. The most common side effects are hypersensitivity, bleeding, hematoma, ptosis, facial spasm, dysphasia or dysarthria. With the use of proper dose and injection sites these side effects can be avoided. PMID- 11760646 TI - [Second-line chemotherapy with paclitaxel for ovarian cancer]. AB - The authors summerize the results of second-line combination chemotherapy with paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 5 mg/ml.min) in patients with recurrent epithelial ovarian cancer. The paclitaxel/carboplatin therapy was applied in 57 patients in 297 courses (median course/patient was 5, range 2, 12). Complete response (CR) was found in 3 patients (3/57 = 5%), however the tumorous process progressed after some time. The median progression free interval (PFI) was found to be 15 (range 3,130) weeks, with an average of 24.3 +/- 26.5 weeks. The authors conclude, that second-line paclitaxel combination therapy produces poorer results than the first-line treatment. These results, which are similar to the literature data have led to the agreement: paclitaxel can be applied in ovarian cancer patients only in first-line chemotherapy in Hungary from the year 2000. PMID- 11760647 TI - [Anti-Saccharomyces cerevisiae antibodies in patients with Crohn's disease]. AB - Inflammatory Bowel Diseases are a group of diseases with chronic inflammation of the gastrointestinal tract, but without proven etiology. Immunologic, environmental, infective and genetic factors equally can play role in their development. Antibodies to an oligomannose epitope of the Saccharomyces cerevisiae demonstrated in 60-70% of the patients with Crohn's disease. The origin and the clinicopathological role are not clarified. It is important that there are no surveys with patients suffering in gluten sensitive enteropathy in the literature. As there are no ASCA survey in Hungary, the aim of this study was to determine the prevalence of the ASCA. The authors examined at their patients the ASCA's occurrence and compared with the clinical picture of the Crohn's disease. The results supported the theory that ASCA positivity correlates with small intestines' Crohn's disease and in these cases both the IgG and IgA type antibodies proved. The antibodies in the sera at the analyzed ASCA positive cases prove a systemic immune response against Saccharomyces cerevisiae and the authors suggest the end of the oral tolerance against the yeast's antigens. The diet restriction (elemental diet, total parenteral nutrition, and fecal diversion) may ameliorate the status of the patients with Crohn's disease. It is speculated that the yeast-free diet as a part of the therapy for the ASCA positive patients can be reasonable: moreover the permanent "forbidding" of the yeast can be an acceptable alternative in case of getting well. PMID- 11760648 TI - [Familial brain abscess as a complication of hereditary hemorrhagic telangiectasia]. AB - The hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an inherited autosomal dominant disease with angiodysplasia of the skin, mucosa, parenchymal organs, and it can affect the central nervous system. In 40% of the cases neurological complications, most frequently intracerebral abscesses occur. In this study, the case history of a patient with central nervous system manifestation of hereditary hemorrhagic telangiectasia showing familiar aggregation of brain abscess will be presented. A young male patient was admitted to Neurological Department because of his first epileptic seizure and progressive right hemispheric symptoms. His examinations showed frontal abscess, which was surgically removed. The frequent nose-bleeding of the patient and recurrent brain abscess in his brother's history provided the possibility of hereditary hemorrhagic telangiectasia. The background of brain abscess were multiple pulmonary arteriovenous malformation, which were embolized by repeated angiography. Familiar brain abscess is very rare. However, in the case of brain abscess especially with familiarity diagnosis of the Rendu-Osler-Weber disease should be considered. PMID- 11760649 TI - [Karoly Laufenauer (1848-1901): the clinical and scientific founder of neurology and psychiatry in Hungary]. PMID- 11760650 TI - [Diagnostic difficulties in the discernment of lymphogranulomatosis. 1926]. PMID- 11760651 TI - [Molecular biology investigations in chronic lymphocytic leukemia]. PMID- 11760652 TI - [Posttraumatic stress disorder in cancer patients]. AB - BACKGROUND: Patients' response to experiencing a life-threatening disease such as cancer is usually marked by high levels of distress. As the latest modification of the stress criterion for posttraumatic stress disorder includes cancer as a potential precipitating traumatic event, the concept of posttraumatic stress disorder has been widely applied to cancer survivors. CURRENT RESEARCH: An increasing number of studies try to assess the traumatic impact of the disease on patients' psychological well-being. The prevalence of posttraumatic stress disorder in cancer patients is still not known, mainly due to various methodological problems and the lack of valid assessment instruments. CONCLUSIONS: The importance of giving clinical attention to the specific stress symptoms in cancer survivors cannot be emphasized enough. Understanding the psychological distress of this population will help clinicians to identify patients at risk and prevent severe stress reactions. PMID- 11760653 TI - [Physical inactivity: a modifiable risk factor in primary prevention?]. AB - BACKGROUND AND AIM: Physical inactivity is an important risk factor for cardiovascular disease and for increased cardiovascular mortality. The aim of this review article was to demonstrate whether increased physical activity can safely reduce the increased cardiovascular mortality due to physical inactivity. A further aim was to derive recommendations for physical activity. METHODS: The effect of physical activity on indirect and direct cardiovascular parameters and clinical endpoints was analyzed by means of an inquiry of the literature. RESULTS: Physical inactivity is an important risk factor for cardiovascular and overall mortality. Many epidemiologic studies could demonstrate with high consistency that regular physical activity is associated with a lower cardiovascular mortality and overall mortality. There is an inverse relationship between physical activity and mortality. Even moderate physical activity (30 min brisk walking or 15 min jogging) on most days of the week can increase the wellness and reduce the cardiovascular and overall mortality. CONCLUSIONS: Regular physical activity can contribute to an enormous health benefit in the general population. Therefore the promotion of adequate physical activity should be a major aim of the policy of health. PMID- 11760654 TI - [Artificial sweeteners--are they potentially carcinogenic?]. AB - BACKGROUND: Artificial sweeteners have rapidly evolved over the last 20 years and are added to a broad variety of food, drinks, drugs, and hygiene products. Since their introduction, especially mass media have reported about potential cancer risks, which has attributed to undermine the people's sense of security. It can be assumed that every citizen of the western countries is using artificial sweeteners--knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. STUDIES: This article gives an overview about the most important publications dealing with the cancerogenic potential of artificial sweeteners. PMID- 11760655 TI - [Hepatocellular adenoma confirmed by Doppler ultrasonography and laparoscopy]. AB - CASE REPORT: A 46-year-old female patient presented for further investigation of an isolated liver lesion that was diagnosed by her physician by abdominal ultrasound and computertomography. The Doppler ultrasound (including a signal amplifier) could not differentiate the lesion so that a laparoscopy was performed. A hepatic adenoma was found which was confirmed by the histological examination of a directed liver biopsy. CONCLUSION: Signs and symptoms, diagnostic procedures and differential diagnostic options of a hepatic adenoma are discussed. PMID- 11760656 TI - [Rescue thrombectomy after stent implantation in a degenerating aortocoronary bypass]. AB - BACKGROUND: Distal showering of atherosclerotic debris or thrombus is a feared event during percutaneous angioplasty of degenerated vein grafts. CASE REPORT: We report on a 66-year-old male patient with a history of coronary artery disease who was admitted into hospital with an acute coronary syndrome. He had had coronary artery bypass graft surgery in 1995. His chest pain resolved under treatment with aspirin, heparin, betablocker, and nitrate. A diagnostic angiogram demonstrated two critical stenoses of the left anterior descending graft. After a continuous infusion of tirofiban administered for 24 h prior to elective angioplasty, a JR 4SH 6 F guiding catheter (Cordis) was positioned. The lesions were crossed with a 0.014" Galeo F wire (Biotronik). A 4 mm x 16 mm stent graft (Jostent, Jomed) was deployed in the distal stenosis and a 4.5 mm x 32 mm self expandable stent (Magic Wallstent, Boston Scientific) in the proximal stenosis. Thereafter, the patient suffered from chest pain, and the ECG showed ST elevation from V1 to V5. Angiography revealed total occlusion of the left anterior descending artery. An X-Sizer catheter (EndiCOR Medical, Inc.) was introduced and advanced through the vein graft with slow back-and-forth movements. After several aspirations, blood flow was significantly improved. A modest CK elevation (127 U/l) indicated a rather small loss of myocardial tissue. CONCLUSION: Percutaneous revascularization of narrowed aortocoronary saphenous vein grafts is associated with increased risk of distal embolization and "no reflow". The X-Sizer catheter system is compatible with commercially available guiding catheters, and capable of retrieving thrombotic debris after macroembolization from degenerated saphenous vein grafts including the native coronary artery. PMID- 11760657 TI - [Lipoid pneumonia following attempted suicide by intravenous injection of lamp oil]. AB - BACKGROUND: Pneumonic complications after intoxication with mineral oils have been described before in the contents of accidental aspiration and oral ingestion. However, intoxication following an intravenous injection leading to a lipoid pneumonia after an attempted suicide is a rare finding. CASE REPORT: A case report is presented of an attempted suicide by intravenously self-injection of 20 ml lamp oil (liquid paraffin). Immediately after injection the patient suffered from dry coughing which changed in the course of the next hours into a productive cough with white thick mucous sputum accompanied by hemoptysis. Additionally, he developed a mild disseminated intravascular coagulation with a fall of thrombocytes, an INR of 1.6 and a rise of D-dimeres. Under a therapy with hydrocortisone, ascorbic acid, ambroxol, acetylcysteine, heparin, antibiotics and oxygen, the patient improved without the need of mechanical ventilation. Initially seen signs of right heart dilatation diminished 3 days after onset of therapy. Apart from pulmonal manifestation no relevant organ damage was observed. The patient was discharged from the intensive care unit 9 days after intoxication and was submitted to psychiatric therapy. CONCLUSION: Lipoid pneumonia caused by intoxication with a mineral oil is a severe disease, whereas in the presented case a relative bland course of the disease has been seen. The employed therapy in this patient might be encouraging for a comparable treatment of pneumological complications resulting from similar clinical pictures. PMID- 11760658 TI - [Pronounced soft tissue calcinosis in primary hyperoxaluria Type 1]. PMID- 11760659 TI - [Individuality in medicine in light of new theory of logic]. PMID- 11760660 TI - [Quality management: internal guidelines and critical pathways for patients]. AB - BACKGROUND: The construction and implementation of "Practice Guidelines" was one of the most important developments in American medicine of the last 15 years. There is ongoing controversy about the effectiveness of these guidelines to get introduced into practice. It has been proved, however, that guidelines developed by care organizations themselves, will show a higher effectiveness and acceptance and will achieve more positive results (Internal Guidelines, "Locally Owned" Standards). "Mipp": Internal Guidelines are also the starting point for the patient pathways of the model of integrated patient pathways "mipp", developed at the Kantonsspital Aarau in the last 7 years. The model is presented with its main features: Construction and Implementation of Pathways, Path-Controlling, Path Benchmarking and Path-Visualization. "Mipp" Pathways share with Clinical Pathways the interdisciplinary perspectives for an efficient quality management. The description of processes is combined with an integrated calculation of costs, which is the basis of standard cost accounting and even activity based-costing. CONCLUSION: In the field of upcoming prospective payment systems (PPS) like ARDRG, APDRG etc. it is of utmost importance for care organizations to have a clear view regarding the treatment processes and the possibilities of their improvement. PMID- 11760661 TI - Toward a genealogy of culture. AB - Using psychoanalytic theory, this paper attempts to trace the natural history of the phenomenon designated as Culture. It postulates that psychoanalysis, a product of the Hegelian philosophical revolution, is still one of the best instruments to understand Culture. It traces the origins of culture as postulated by Freud and the pioneer anthropologists and its course from early and evolved religion through humanism, science, and finally postmodernism. It emphasizes the dialectical concepts in psychoanalysis and reviews summarily those psychoanalysts that, according to the author, have had a major impact on the study of culture: Freud, Horney, and Lacan. PMID- 11760662 TI - The gap between: being and knowing in Zen Buddhism and psychoanalysis. AB - The author discusses various relationships derived from the image of gap, precipice, and abyss with specific emphasis on interacting dynamics between being and knowing as explicated in the Zen Buddhist teachings of Hui-neng and in the psychoanalytic writings of Wilfred Bion. While of significant value to psychoanalysis, it is argued that symbolic meanings can occlude the actuality of the analysand's or of the spiritual seeker's affective experiencing, particularly concerning the human tendency to concretize experiential states engendered through meditation and/or the psychoanalytic encounter. The author draws from Matte-Blanco's explication of symmetrical and asymmetrical perceptual modalities to discuss the fluid nature of spiritual experiencing, paradoxical coexistence of ultimate and relative realities and reciprocal dynamics and identities between states of experiencing that might otherwise appear opposed. The primacy of experiencing for both disciplines, particularly concerning the experiencing subject's momentary state of consciousness, forms a central theme for both Zen and psychoanalysis. Brief clinical vignettes support and illuminate the author's points. PMID- 11760663 TI - Phantasies, neurotic-beliefs, and beliefs-proper. AB - This paper presents a philosophical analysis of three cognitive states familiar and important to psychoanalysts--phantasy, neurotic-belief, and belief-proper. It explores the differences among these three propositional attitudes and finds that the development of secondary process capacities of reality testing and truth directness out of earlier primary process operations (themselves prior to considerations of truth or falsity) plays a crucial role. Difficulties in the proper typing of cognitive states are discussed, as are the consequences of such confounds. This use of a philosophical method serves to sharpen the familiar psychoanalytic clinical concepts of phantasy and neurotic-belief. In addition, these same clinical concepts, once properly specified, have much to offer the philosophy of mind, where current understanding of representational cognitive states is restricted to those that are largely conscious and rational. When psychoanalytic concepts such as phantasy and neurotic-belief can be better integrated within the discipline of philosophy of mind, both philosophers and psychoanalysts will have a more complete and adequate theory of mind. PMID- 11760664 TI - Elasticity of technique: the psychoanalytic project and the trajectory of Ferenczi's life. AB - The object of this paper is the Elasticity of Psychoanalytic Technique in the work of Sandor Ferenczi. The author sustains that this can be considered neither as an ultimate arrival point nor as a particular stage of Ferenczi's clinical theoretical body of work, but rather as an ensemble of affective qualities, attitudes and values, which he gradually developed through experience, signalling a paradigm shift in the history of psychoanalysis. The following areas will be explored: the new sensitivity demonstrated by Ferenczi concerning the relational and communicative factors present in the analytic session, his subtle and acute attention to the participation of the analyst's own subjectivity in the therapeutic process, and how these enduring elements of Ferenczi's technique anticipate several significant future developments in psychoanalysis. PMID- 11760665 TI - Gender in homosexual boys: some developmental and clinical considerations. PMID- 11760666 TI - [The return to home for children at the end of life]. PMID- 11760667 TI - [How and when to decide to stop curative treatment? Pediatric oncology experience]. PMID- 11760668 TI - [Intestinal volvulus in extremely premature infants]. AB - Volvulus with or without malrotation are infrequent in the extremely premature newborn. CASE REPORTS: Intestinal volvulus in seven premature newborns are reported with abdominal distention, bright and tense skin without visible bowel loops and spiraled bowel loops on the abdominal X-ray. Intestinal resection was avoided due to early diagnosis. We identified abdominal wall massages as a risk factor, because no new cases have occurred since interdiction of these practices. CONCLUSIONS: Symptoms and radiologic findings are relatively specific for excluding the diagnosis of necrotizing enterocolitis in premature newborns. Abdominal nursing could be the incriminating factor. PMID- 11760669 TI - [Treatment of giant congenital nevus with high-energy pulsed CO2 laser]. AB - All authors agree upon the need for early treatment of giant congenital nevi. The surgeon must seek to minimize the risk of malignancy. The objective calls for radical excision of all pigmented areas; this may be impossible because of the risk of leaving the patient with disfiguring scars. The aim of this study was to assess treatment of giant congenital nevi with the high-energy pulsed CO2 laser as an alternative to surgery. PATIENTS AND METHODS: Between 1998 and 1999, the high-energy pulsed CO2 laser was used in nine newborns and five children. RESULTS: The treatment with the high-energy pulsed CO2 laser achieved 70-90% clearing of the giant nevi in most of the children. Two children developed hypertrophic scars on a companion nevi and on giant congenital nevi. One child required a skin graft because of tissue necrosis, associated with a disseminated intravascular coagulation and septic shock. DISCUSSION: Laser is a surface technique proposed when surgical excision cannot be performed because the surface is too large or the localization is incompatible with surgery. Early treatment, in the first 15 days, is not required for the quality of the cosmetic result. The high-energy pulsed CO2 laser provides satisfactory cosmetic results with short cicatrisation time. It allows the treatment of the companion nevi at the same time. The risk of malignant transformation is greatly but not totally reduced. Regular clinical surveillance should help reduce the risk. PMID- 11760670 TI - [The lessons of medical cooperation (1995-1998): the formation of young teams trained in emergency services at two Romanian pediatric hospitals]. AB - A cooperation programme, aimed at improving the running of pediatric hospitals in Bucharest (Romania) was conducted by a team of Assistance Publique-Hopitaux de Paris from 1995 to 1998. MATERIAL AND METHODS: The introduction mentions the context of the health care system in order to help to follow the role of emergency services. The method to improve the child health services was based on an initial evaluation of emergency structures and procedures. A questionnaire was filled in after a four-year programme to test the impact of the counselling concerning the organization of the casualties and emergency division, the medical and nursing training and the use of equipment. RESULTS: The results show: a centralization of the emergencies and the implementation of an intensive care unit in one out of the two hospitals. The discussion points out the criteria of efficacy for cooperation programmes and gives examples of medical cooperation in eastern countries. CONCLUSION: The conclusion insists on the multidisciplinary approach of medical programmes, with training of young teams. PMID- 11760671 TI - [Nutritional status and risk in hospitalized children]. AB - BACKGROUND: A few studies report malnutrition in hospitalized patients. MATERIAL AND METHODS: This one-day cross-sectional survey performed in January 1999 assessed nutritional status and protein-energy intake in a pediatric population hospitalized in medicine or surgery units. Every child older than six months, hospitalized for more than 48 h and free of nutritional support (parenteral, enteral, or special regimens for metabolic diseases) was included. RESULTS: Fifty eight children among the 183 present the day of the study met the inclusion criteria and were included in the statistical analysis. They were hospitalized in medicine (48%), psychiatry (31%) and surgery (21%). The body mass index (BMI) was below -2 standard deviations (DS) in 21% of them. Excluding patients with anorexia nervosa, BMI was < -2 SD, > +2 SD, or in between these limits in respectively 12, 14 and 74%. Energy intake measured at the hospital was below 75% of the recommended dietary allowances in two-thirds of the children whether malnourished or not. Fifty percent of the malnourished children had been referred to a dietician the day of the study. CONCLUSIONS: Malnutrition is frequent in a population of hospitalized children. Energy intake and referral to a dietician are insufficient. PMID- 11760672 TI - [Mayer-Rokitansky-Kuster-Hauser syndrome: associated pathologies]. AB - MRKH syndrome (Mullerian structures agenesis in woman) is often associated with other anomalies: kidney and bone anomalies, deafness, ovarian tumors. Functional ovarian anomalies have not been previously reported. CASE REPORTS: Five new cases of MRKH syndrome are reported. They were associated with deafness in two cases, with kidney anomaly in three cases, vertebral anomalies in one case, and four suffered from obesity and ovarian dysfunction (ovarian polycystics syndrome, advanced puberty, androgenic excess). All of them had ovarian ectopy, which was responsible for false ultrasonographic diagnosis. CONCLUSION: An MRKH syndrome diagnosis implicates a search for other anomalies. Ovarian functional trouble should not let MRKH syndrome remain unrecognized. PMID- 11760673 TI - [Laryngitis revealing bacterial tracheitis in a five-year-old child]. AB - CASE REPORT: We report the case of a five-year-old boy with clinical features of croup and left lower lobe pneumonia. Response to inhaled adrenaline and dexamethasone was incomplete and he developed respiratory distress. Direct laryngoscopy performed in the operating room showed mild glottic and subglottic inflammation. On bronchoscopy, there was thick pus coming from the left lower lobe. He was intubated for three days and regular toilet brought back thick pus. Tracheal fluid culture grew Haemophilius influenzae. COMMENTS: We suggest that he had bacterial tracheitis but that the tracheal involvement was not prominent at the time of diagnosis. CONCLUSION: Laryngoscopy and bronchoscopy in specialized surroundings should be considered for each child with croup unresponsive to conventional treatment, especially in case of lower respiratory tract involvement. PMID- 11760674 TI - [Aerosolized iloprost therapy in an infant with chronic pulmonary hypertension after a neonatal arterial switch operation]. AB - The treatment of chronic pulmonary hypertension with prostacyclin in children is prone to severe complications due to mandatory long-term venous therapy. Inhaled iloprost has been evaluated in adult patients with good preliminary results. CASE REPORT: We report our experience of the use of aerosolized iloprost in an infant treated for pulmonary hypertension associated to a right ventricular failure, which occurred after a neonatal arterial switch operation for transposition of the great arteries. For nine months, hemodynamic and functional status improved and the quality of life was satisfactory at home. CONCLUSION: If further experiences and studies support this observation, aerosolized iloprost could be an alternative to prostacyclin venous therapy in treating children with chronic pulmonary hypertension. PMID- 11760675 TI - [Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden and prothrombin mutations]. AB - We report a case of renal vein thrombosis, treated with heparin and thrombolytic therapy, in a patient who was heterozygous for both factor V Leiden and prothrombin mutations. CASE REPORT: A full-term infant was treated with heparin and fibrinolytics at the fourth day of life because of renal vein thrombosis, inferior vena cava thrombosis and adrenal hemorrhage. After four days of treatment, the repermeabilization was complete but a renal atrophy developed. The investigation for congenital coagulation disorders revealed a heterozygous mutation for both factor V Leiden and prothrombin. CONCLUSION: Search for inborn blood coagulation disorders should be systematic in the newborn infant with venous thrombosis because of the risk of recurrence, even in the presence of a known acquired risk factor. The thrombolytic treatment improves the prognosis. PMID- 11760676 TI - [Infant formulas and soy protein-based formulas: current data]. AB - For many years soy bean-based formulas (SBBF) were the only dietary product used for infants with cow's milk intolerance. At the present time, their place in infant nutrition is reduced as a result of the availability of new dietary products without lactose and/or cow's milk proteins and the recognition of soy bean protein allergy. There is no evidence that SBBF have any efficiency in infant colic. SBBF have no indication in the prevention of allergy, nor in premature infants' nutrition. Their main indication is the feeding of infants of vegetarian parents who do not want to use cow's milk products. Studies have shown that SBBF contain large quantities of phytoestrogens, particularly isoflavone. Because of experimental data suggesting a possible deleterious effect of phytoestrogens on the neuroendocrine maturation, the reduction of their content in SBBF must be considered. PMID- 11760677 TI - [Radiology case of the month. Blount's disease]. PMID- 11760678 TI - [Guilt and aggression in children after the death of a relative]. AB - Children may feel guilty about the death of a close relative. The reasons are analyzed: in most cases guilty feelings remain unjustified. Consequent changes in the child's behavior are described, including aggressivity, depressive symptoms and regression. A preventive comprehensive attitude of the surviving family circle will help children to overcome these feelings. PMID- 11760679 TI - [Bicycle helmet effectiveness in children: qualitative analysis of the literature]. AB - In order to assess bicycle helmet effectiveness in preventing head injury in children, we performed an international qualitative and systematic review using the criteria of the French Health Accreditation and Evaluation National Agency (ANAES) developed for recommendations in clinical practice (formulation of a question, judgment criteria, collecting references, quality analysis, interpretation of results). Two hundred and thirty-four papers dealing with the subject were identified through a MEDLINE search. Two hundred and fifteen of them were eliminated as they did not meet selected criteria. Four were eliminated because of language criteria. On the 14 meeting all selection criteria, five were judged satisfactory according to qualitative criteria. All five conclude in favor of the effectiveness of the bicycle helmet even when taking bias into account. The real protection afforded by wearing a bicycle helmet militates in favor of its habitual use. PMID- 11760680 TI - [Adolescents and contraception. What should the pediatrician know? (Part one)]. AB - Many adolescents are sexually active and reproductive health is an important aspect of adolescent medicine. However, pediatricians are often uncomfortable with the issues of sexuality and contraception, for which they have not been particularly trained. The general purpose of this article is to increase pediatricians' sense of competence with adolescents, particularly when having to deal with or counsel on such a sensitive issue as contraception. This first of two parts is an updated review of the relevant contraceptive methods available, mainly condoms and various contraceptive pills, but also less-prescribed method like long-term progestins, as well as the recently debated emergency contraception. Each of these methods is described in its context of use at adolescence. PMID- 11760681 TI - [Infants born by cesarean section at the University Hospital Center of Brazzaville]. PMID- 11760682 TI - [Bacterial meningitis in children at the University Hospital Center of Bouake in the Republic of the Ivory Coast]. PMID- 11760683 TI - [Rectal bleeding: complication of hydrogen peroxide enemas]. PMID- 11760684 TI - [Role of nutrition in postnatal cytomegalovirus infection in premature infants]. PMID- 11760685 TI - [Reply to the open letter from an urban pediatrician to his hospital colleagues]. PMID- 11760686 TI - [Reply to an open letter from an urban pediatrician to his hospital colleagues ]. PMID- 11760687 TI - [Incidence of Reye's syndrome in France]. PMID- 11760688 TI - [Relationship between vaccination for diphtheria-tetanus-pertussis +/- Haemophilus influenzae b and sudden infant death before three months of age: a case-control study]. PMID- 11760689 TI - [Prospective study of post-traumatic stress in victims of terrorist attacks]. AB - In 1995-96 several terrorist attacks struck Paris. After that, the French government decided to optimize the service claimed to treat psychological repercussions of attacks victims. For this reason we need to better understand the psychopathology developing after these traumatic events in order to adjust the various steps of the treatment. In December 1996, a terrorist attack occurred in a Paris subway. Medical and medico-psychological teams intervened immediately on the site to help victims. Among 115 victims, 4 persons died and 35 were seriously injured. The aim of our study was to evaluate the psychological impact among a population of terrorist attacks victims by a prospective study and to identify predictive factors of posttraumatic stress disorder (PTSD). We evaluated PTSD rates at 6 and 18 months, the relationship between coping style and PTSD, and whether PTSD increased health care utilization. Two follow up evaluations were performed in the 6th and 7th month respectively, by means of self questionnaires sent by mail. Among 115 victims of the bombing attack occurred in December 1996, the 111 survivors were asked to participate to the study. The subjects who accepted and could use French questionnaires were considered eligible for the inclusion: the main criteria of the Watson's PTSD Inventory for the specific post-traumatic symptoms were used; the Goldberg's General Health Questionnaire was used to measure the general psychopathology; to identify coping styles we used the questionnaire "Ways of Coping Check List" of Vitaliano at 6 months and the "Coping Inventory for Stressful Situations (CISS)" by Endler at 18 months; a small questionnaire was proposed to evaluate injuries, hospitalization and specific treatment immediately or after the event. Among 70 subjects who accepted to participate, 56 (33 females) could be evaluated at 6 months and 32 (14 females) subjects at 18th months. The mean age at 6 months was 38.4 years: 41% of participants met PTSD criteria at 6 months, 34.4% still had PTSD at 18 months; at 18th months, 50% subjects presented GHQ scores higher than 3, corresponding to the cut-off revealing mental suffering; people hospitalized more than two days immediately after the event presented significantly lower PTSD scores at 6 months. General characteristics of risks factors for PTSD were: at 6 and 18 months, women and younger people presented significantly higher PTSD scores; for the CISS at 18 months Emotion-oriented coping correlated significantly with PTSD (r = 0.49, p = 0.007), while task-oriented coping and PTSD correlated negatively (r = -0.39; p = 0.04). Avoidance coping's styles were not correlated with PTSD. About predictive factors: the GHQ-12 and PTSD-I scores at 6 months were significantly correlated with PTSD-I scores at 18 months (respectively r = 0.73, p = 0.018 and r = 0.75, p = 0.0029); by a multiple regression we observed that PTSD-I score at 6 months predicted the PTSD-I score at 18 months, adjusted on sex and age. The others characteristics at 18 months were: medication use increased significantly at 18 months; people who lived another traumatic event since December 1996 presented a 18 month PTSD score higher than the other victims. In spite of the small size of this sample, the principal interest of this study is the prospective data in a population exposed by the same traumatic event. We note the high score of PTSD at 18 months. Terrorism exposure resulted in persisting PTSD in a significant proportion of victims; this was related to coping style. Moreover PTSD increased health care utilization. We discuss these results comparing with other similar populations in France, Israel and USA. We discuss overall the role of coping styles during the time after an attack; we insist on considering this aspect in the therapeutic strategies. These data contribute to inform that people with a high PTSD score at 6 months presented a high risk to suffer PTSD at 18 months. These results underline the importance of early diagnosis to propose early medical and psychological help to the victims. PMID- 11760690 TI - [Hypofrontality and negative symptoms in schizophrenia: synthesis of anatomic and neuropsychological knowledge and ecological perspectives]. AB - Cognitive deficits in schizophrenia have been observed with neuropsychological tests of executive function, traditionally considered sensitive to frontal lobe damage. These impairments affect planning abilities, as well as the aptitude to initiate and regulate a goal-directed behaviour. On the other hand, negative symptoms of schizophrenia are widely suspected to reflect a frontal lobe dysfunction. Based on a review of a hundred papers, the present article analyses the anatomical and neuropsychological evidence of disturbed frontal lobe functioning in patients with negative schizophrenic symptoms. The phenomenological similarity of some schizophrenic symptoms to the clinical features of patients with prefrontal injury inspired the hypothesis of damaged frontal lobe in the former disorder. The morphological findings of neuroimaging studies brought inconsistent conclusions, with some researchers noting no differences between patients and control subjects while others observing reduced prefrontal volumes in schizophrenia. The functional neuroimaging demonstrated a reduced frontal blood flow relative to the general cerebral perfusion in patients with schizophrenia. Even though the overall neuroimaging literature provides reliable evidence of frontal impairment in schizophrenia, the average magnitude of the difference between patients and healthy controls is insufficient to defend the hypothesis of frontal lobe dysfunction, as far as brain volume, resting metabolism or blood flow are concerned. The only measure, which clearly distinguishes between the patients' and controls' distributions, is the functional neuroimaging of the frontal lobe while subjects are performing an experimentally controlled task. Schizophrenic patients fail to activate their frontal cortex when the task requires it. Analysing executive abilities in relation to symptom expression leads to recognising the fact that frontal dysfunction is a characteristic of only a sub-syndrome of schizophrenia. The factor analysis of the clinical features consistently reveals three syndromes in schizophrenia, termed disorganisation, positive and negative syndromes. The substantial body of evidence that patients exhibit more than one syndrome indicates these are dimensions within a single illness rather than discrete diseases. Liddle labelled the negative syndrome as "psychomotor poverty" and associated it with malfunction of the neuronal projections from dorsal prefrontal cortex to thalamus via striatum, connections involved in the initiation of mental activity. His hypothesis was supported by the work of other, independent research groups. The patients with negative symptoms, in contrast with the nonnegative symptom group, tend to demonstrate reduced neuronal activation of the frontal cortex during executive task realisation. The nonnegative patients are indistinguishable from the healthy control subjects in this region. Neuropsychological studies reveal that severity of psychomotor poverty is associated with slowing of mental processing and deficits in tasks that require planning abilities. These frontal functions are identified with the selection, the initiation and monitoring of a wide variety of behavioural processes. It was hypothesised that executive dysfunction will appear through different patterns across symptom subtypes, but few studies sought to validate this assumption. Finally, researchers make little effort to develop theoretical conceptualisations of the aetiology of negative schizophrenic symptoms, despite the growing body of evidence on its resemblance to the dorsolateral frontal lobe syndrome. Frith proposes that defects in the initiation of spontaneous action underlie these clinical phenomena, but his definition is not specific enough to be confronted to existing literature, neither has been empirically tested. Disturbed executive functioning has detrimental impact on the quality of daily living in patients with schizophrenia. Indirect observation of the latter accounts for defective long-term adaptation, which has been correlated to severity of negative symptoms and, although not consistently, to executive deficit as assessed by neuropsychological testing. Unfortunately, this area of research lacks ecologically valid studies. Measuring executive dysfunction as it occurs in the natural setting of the patient and validating dissocialbility of frontal deficits with respect to the schizophrenic symptomatology could lead to greater individualization of treatment plans and therefore to more efficient therapy outcome. PMID- 11760691 TI - [Typology of elderly patients hospitalized in psychiatry: evaluation of psychiatric antecedents before age 60]. AB - To take care of elderly patients in psychiatric hospital sets specific problems. It is interesting to know the mode, the frequency, and the reasons of these hospitalizations, to improve the medical care given to these subjects. We made a prospective study with elderly patients hospitalized in a psychiatric institution. The results were completed in discussions with the medical care staff. During the study (January and February 1997), 112 elderly patients, about more than 60 years old, were hospitalized in Villejuif' specialized hospital (inpsychiatric units). Informations about social facts, main psychiatric previous, reasons of the hospitalization, the caring and the evolution of these subjects were collected. The main important reflexion we did observe was the significant difference between elderly patients hospitalized in psychiatric units, with or without psychiatric previous before the age of 60. Those who were hospitalized at the first time in psychiatric units before 60, presented a medium aged population, younger than the other group. They also presented more delusion with psychosis, were more frequently hospitalized longly in psychiatric units, took neuroleptics, and their somatic associate pathologies were less difficult to take care of. In the second group including the elderly patients without psychiatric previous before 60, we did observe very different characteristics: the diagnosis of most of the patients is dementia; these elderly subjects leaved mostly at home, they presented more sadness, aggression, or social inappropriate behaviour. Depression is a more frequent diagnosis. This study of all the elderly patients admitted in a psychiatric hospital confirmed the population's heterogeneity. The existence of an hospitalisation in psychiatric unit before sixty represented a pertinent test to a major and simple approach of these differences. The psychiatric unit which receives more and more elderly patients take care of their differences to the organisation of care needs between the gerontopsychiatric patients types. The patients with a late gerontopsychiatric's disease could need a specific hospitalization in gerontopsychiatric units, especially organised to deliver psychiatric cares and somatic cares, including medical geriatric practicer and medical care staff formed to the dependence need care. PMID- 11760692 TI - [Correlation between eating disorders and sleep disturbances]. AB - Anorectics and bulimics often complain sleep onset insomnia and disrupted sleep. During awakenings bulimics can have binges. Conversely, eating disorders can be a clinical expression of a concomitantly occurring sleep disorder. Two clinical entities have been recently described: the Night Eating Syndrome (NES) and the Sleep Related Eating Disorders. The main goal of this literature review was to better characterize the relationships between eating disorders and sleep disturbances. No specific EEG sleep pattern emerges in anorectic and bulimic patients. However, all studies include several methodological limitations: a few number of patients, heterogeneous patient groups, various diagnostic criteria. The results of studies evaluating the impact of depression on sleep EEG in eating disorder patients are also subject to controversy. The only study examining the relationship between sleep EEG and morphological alterations in anorectics and normal weight bulimics shows that patients with enlarged cerebrospinal fluid spaces spent more time in slow wave sleep and that the duration of rapid eye movement (REM) sleep was reduced. The ventricular brain ratio was negatively correlated with REM sleep. The Night Eating Syndrome consists in insomnia, binge eating and morning anorexia. Other criteria are proposed to characterize the NES: more than 50% of the daily energy intake is consumed after the last evening meal, awakenings at least once a night, repetition of the provisional criteria for more than 3 months, subjects do not meet criteria for bulimia nervosa or binge eating disorder. Patients have no amnesia nor alteration of alertness, and no other sleep disorder. There is no modification of sleep EEG except sleep maintenance. The prevalence of the NES is 1.5% in the general population. Some neuroendocrine disturbances have been found in the NES. The delimitation with eating disorders is not yet clearly established. If it shares the compulsive features with eating disorders, particularly the "Binge Eating Disorder", and occurs during full awakenings, the night eating syndrome may be recognized as a specific eating disorder. The sleep related eating syndrome is also characterized by compulsive binge eating during awakenings. But in this case, night eating is linked with a reduced consciousness and sleep disorders, mainly somnambulism. Patients never experience hunger, abdominal pain, nausea or hypoglycemia. Night-eating takes place invariant across weekdays, weekend and vacations. Patients consumed high caloric foods and fluids but never alcohol and purging does not occur. Diurnal bulimia is frequently associated with the sleep-related eating disorder. In conclusion, the sleep related eating disorder seems rather be a clinical subtype of sleep disorders whereas the NES could be considered as an eating disorder. PMID- 11760693 TI - [Prescribing ritalin in combined modality management of hyperactivity with attention deficit]. AB - Attention Deficit Hyperactivity Disorder (ADHD) is a relatively frequent affection that can generate severe problems (school, social, professional) if no take in charge is done. Treatment of ADHD is generally multifactorial; it can associate medical treatment, comportemental and analytical psychotherapies, reeducation of associated disorders (orthophony, psychomotor reeducation) and educative approach. Methylphenidate, considered as therapeutic reference, is a central nervous system stimulant. It produces a stimulation of vigilance and superior mental activities, a diminution of fatigue sensation and sleep need, an anorexigen power and sympathomimetic effect. Its mechanism of action is abundantly studied and is not completely known. Principal hypothesis are: increase of chemical mediators biodisponsibility and change in cerebral blood flow delivery. In France, it is agreed since 1995 for treatment of ADHD in over 6 years-old child. Ritaline 10 mg is registered on the narcotic list and an initial hospital prescription is needed, reserved to specialists and/or to neurologic, psychiatric and pediatric services. Mid-1995, 2.8% (namely 1.5 millions) of 5 to 18 years-old american children have taken this drug. Methylphenidate is effective on each three principal symptoms of ADHD: it decreases the level of activity, it improves apprentice capacity, just as school performances and it eases social interactions. The therapeutic schedule at short and middle term is reassuring, with substantial profits on school, familiar and social plans, but unknowns subsist and opinions diverge about long term efficacity. Methylphenidate is not the only one used in ADHD treatment. Other products, like dextroamphetamine and pemoline have been used in the USA and are for those who can't tolerate methylphenidate or badly respond to it. Those other drugs are not commercialized in France. The limits of stimulating drugs (fear to favour toxicomania, undesirable effects that need to stop treatment or non-responsive hyperactive children), just as positives experiences with antidepressants (especially on enuresis) led to use tricyclic antidepressants as second-line agents in ADHD treatment. Their efficiency is less and their well known side-effects are sometimes constraining. Antidepressants that inhibit serotonin recapture, MAOI and bupropion, central antihypertensive, such as clonidine and guanfacine have been tried in ADHD treatment as third-line agents. They should be useful on non responsive or patients who can't tolerate stimulants or tricyclic antidepressants. Analytical and comportemental psychotherapies are used in addition to medicamental treatment. Reeducation of troubles such as dyslexia, language delay, corporal scheme troubles or fine coordination trouble is obtained by orthophony and psychomotricity. It's very important to instaurate an educative strategy in order to contend inattention and hyperactivity. Regular conservations with parents and child are necessary. The whole american literature shows better efficiency of multimodal treatment of ADHD in child, as opposed to single stimulant treatment. PMID- 11760694 TI - [Schizophrenia and performance on the Wisconsin Card Sorting Test (WCST): deficits and rehabilitation]. AB - In recent years, there has been a sustained interest in the so-called "frontal hypothesis" of schizophrenia: the idea that clinical symptoms and cognitive deficits characteristic of schizophrenia might be explained by defective function of the frontal lobes. Several studies have attempted to test this hypothesis by examining the performance of schizophrenic subjects on the Wisconsin Card Sorting Test (WCST), a neuropsychological evaluation widely believed to reflect the functional capacity of frontal lobes. A typical finding is that schizophrenic patients demonstrate a tendency to perseverate in producing an inappropriate response in spite of negative feedback. This perseverative tendency resembles the perseveration often seen in patients with frontal brain damage. This article proposes a critical examination of the available evidence linking frontal deficits with schizophrenia via the WCST. As we will show, in most of these studies, only a relatively small number of the available measures on the WCST are made, and consequently many interesting cognitive capacities in schizophrenic subjects have not been adequately examined with this test. These "non-classical" measures will be described and critically examined with respect to their pertinence for further work on schizophrenic subjects. Of particular interest are the "failure to maintain set", which measures cognitive instability, "conceptual responses", which can indicate a certain conceptual capacity even in subjects who show perseveration, and "learning to learn", which can demonstrate a capacity to profit from experience on the test. A second objective will be to critically examine the evidence concerning the capacity of schizophrenic patients to improve their performance on the WCST. To the extent that performance on the WCST reflects the functional level of cognitive capacities important for everyday life, any capacity in schizophrenic patients to improve their performance could have important implications for therapeutic intervention and re-education. PMID- 11760695 TI - [Development of a scale for assessing lack of motivation in elderly persons]. AB - OBJECTIVE: Apathy is made of depression and of loss of motivation. For patients with senile dementia of Alzheimer-type, the MMS score is inversely correlated with apathy and depression. The aim of this study is to build a scale aimed at loss of motivation and validated for elderly people. METHODS: The study was performed on 44 non-demented elderly people, 54 outpatients with dementia, mainly Alzheimer's type. After agreement of the patients and the family, patients were assessed using different scales: Cornell's for depression, Marin's for apathy, MMS for cognitive disorders. At the same time, we tested with caregivers a 21 items indirect scale listing various disorders related to loss of motivation, scored from 1 to 4: very often, often, sometimes, never. Patients were retested by 7 different caregivers, and different investigators, immediately and a month later to evaluate reproducibility, temporal stability using Cohen's Kappa and Spearman coefficients. The demotivation scale was then correlated with the other scales and Cronbach's alpha coefficient was studied. RESULTS: The 44 non-demented people were 80.25 years old +/- 7.75. 54 demented patients were included: 15 men and 39 women. The mean age was 81.47 years +/- 8.03. As Cohen's Kappa and Spearman coefficients were not sufficient for 6 items, the scale was reduced to 15 items (Presented). The depression scale is strongly and significantly correlated with the Marin's apathy scale. Internal coherence is particularly significant: Cronbach's alpha coefficient = 0.91. For the 54 patients with dementia, the depression score worsens significantly as cognitive disorders worsen. In these patients Marin's scale shows a progression of apathy with the impairment observed in MMS, but the MMS is not correlated with the score at the demotivation scale. So this latter scale seems to measure something close but independent from apathy. DISCUSSION: The loss of motivation is a frequent behavioral disorder in old patients. Loss of motivation can be present in any chronic disease with asthenia. This disorder is frequent in depression, in dementia and even in endocrine disease, for instance hyperthyroidism. It triggers a loss of commitment of old people and paves the way for the loss of autonomy. Apathy is a loss of motivation associated with an affective blunting. Demotivation is congruent with the actual presence of apathy in patients as measured using Marin's scale that has been used as a standard in this study. This paper presents a methodology for an evaluation scale aimed at the loss of motivation in old people. A psychologist and seven different caregivers working in a day care hospital on 98 patients performed an indirect assessment. An estimation of specificity, sensibility, reproducibility and homogeneity was tested with appropriate techniques. The results obtained with this scale answer the preliminary methodological queries, allowing us to trigger further researches for a final validation. According to our results, demotivation does not increase with age neither in demented nor in non-demented patients. Conversely, the aggravation of cognitive disorders in dementia is associated with increasing demotivation and depression. The loss of motivation participates to the learnt and acquired helplessness. Its care is necessarily global, using pharmacological, psychological and sociotherapeutic treatment. CONCLUSION: EAD scale appears a reliable tool to assess loss of motivation in old and very old patients. PMID- 11760696 TI - [Benzodiazepine addiction and symptoms of anxiety and depression in elderly subjects]. AB - The relative works to the psychopathological aspects of benzodiazepines (BZD) addiction in elderly persons make the object of a large debate because the question of addiction remains whole. They concern: 1) the influence of age on the level of consumption of the BZD. The research permits to clear 4 explanatory major factors of the relation observed between age and the consumption of BZD: a) the morbidity increased of the aged people, b) the impact of the painful life events, c) the social isolation, d) the weight of the medical prescription; 2) the concepts of dependence (evolution of the definitions, type of physical, psychic or psychopathological dependencies) and of addiction (definitions, place in the international classifications, psychopathological perspective); 3) the reports of the anxiety and the depression with BZD addiction in elderly persons. To the look of these works, the objectives of this present study were to examine the variability of BZD addiction on the one hand within a population weakened by the effects of age (apparition of a chronic illness, for example) and on the other hand the relations that the anxious and depressive symptoms maintain with BZD addiction in elderly persons. Two self-questionnaires were administered: 1) BZD addiction scale, 2) Hospital Anxiety Depression Scale (HAD) to 28 elderly (18 women and 10 men; mean age is 73.25 years). To the exit of this work, the results put in evidence go in the sense of our hypotheses but cannot be generalized to the set of the elderly consumers of BZD, they let appear that age, the depression and the association anxiety/depression predict meaningful manner BZD addiction. Indeed, with regard to age, the polypathology as well as the changes of life induced by the aging process involved BZD addiction in old people. The old age can engender a depression that results in addictive behavior. However, anxiety alone is not experienced before drug addiction in a significant way. This result can explain itself by the fact that the anxiety is a symptom of depression. The present research is unique in several important aspects. First, the study shows that drug addiction in old people cannot be reduced to physiological addiction on product but understood in terms of a complex process requiring an analysis of the psychological addiction on product. Second, BZD addiction in the elderly acts as a psychological/existential medical care. Future research is needed to examine the psychological and psychopathological links that old people maintain with their drug medication. PMID- 11760697 TI - [Evaluation of worry: validation of a French translation of the Penn State Worry Questionnaire]. AB - Excessive worry, which is the central feature of Generalized Anxiety Disorder (GAD), is recognized as an important clinical phenomenon with many negative consequences on people's health. For example, studies report that excessive worry is associated with higher frequencies of work absenteeism and medical consultations, increased risk of other anxiety disorders, depression, heart disease, diabetes and cancer. It is thus imperative to develop effective measures to assess worry among adult. Until now, no measures were available in French for the practitioners and researchers to evaluate the tendency to engage in excessive and uncontrollable worry. One of the most frequently used questionnaires to assess worry in English is The Penn State Worry Questionnaire (PSWQ). This self report measure has been widely studied and has shown excellent psychometric properties among the non-clinical and clinical populations. This manuscript presents the results of three studies evaluating the psychometric properties of a French Translation of the PSWQ, the Questionnaire sur les Inquietudes de Penn State (QIPS). The first study includes the translation procedures used to create the French version of the questionnaire, the factorial structure, the internal consistency, the quality of the items, and the convergent validity among non clinical participants. The second study examines the temporal stability, and the convergent and divergent validity of the questionnaire. Finally, the third study investigates the internal consistency, the quality of the items, and the convergent and divergent validity of the questionnaire among GAD patients. Study 1. This study describes the translation procedures used to create the QIPS, the factorial structure, the internal consistency, the quality of the items, and the convergent validity among non-clinical participants. The French version was translated by a group of clinical psychologists with the assistance of a professional translator and a linguist. A back translation procedure was also conducted. Finally, a pilot study confirmed the intelligibility of the questionnaire. French-speaking university students (N = 352) completed a battery of questionnaires during a lecture. The questionnaires were: The Questionnaires sur les Inquietudes de Penn State, the Intolerance of Uncertainty Questionnaire, the Cognitive Avoidance Questionnaire, the Why Worry Questionnaire-Revised, and the Social Problem-Solving Inventory-Revised. The statistical analyses reveal that the QIPS shows an appropriate factorial structure, an excellent internal consistency and a very good convergent validity. This French Questionnaire thus seems to be suitable to assess the tendency to worry among the nonclinical population. Study 2. This second study examines the temporal stability, and the convergent and divergent validity of the QIPS. The sample includes 95 French speaking University students who volunteered to complete the QIPS and the Beck anxiety Inventory. Two self-rating questions were also asked to evaluate the percentage of time spent worrying and to what extent does worrying causes a problem. Eighty-six students participated at the second administration of the questionnaires, four weeks later. The results indicate that the QIPS is very stable over time, thus supporting its temporal stability. Different correlations confirm its convergent and divergent validity. It is concluded that the QIPS is a suitable measure of worry in a non-clinical population. Study 3. This study investigates the internal consistency, the quality of the items, and the convergent and divergent validity of the questionnaire among GAD patients. Seventy-seven GAD patients, as defined by the Diagnostic and Statistical Manual of Mental disorders, fourth edition (DSM IV), participated in this study. They completed the QIPS, the Worry Domains Questionnaire, The Worry and Anxiety Questionnaire, the Intolerance of Uncertainty Questionnaire, the Beck Anxiety Inventory, the Beck Depression Inventory, and a daily diary of differents aspects of worry. The results reveal that the QIPS has an excellent internal consistency, a very good convergent and divergent validity. The QIPS thus seems to be suitable to assess the tendency to worry among GAD patients. CONCLUSION: The overall results presented in these studies confirm the excellent psychometric properties of the QIPS. This French questionnaire is a useful tool for clinicians and researchers to assess the tendency to worry among non-clinical and clinical populations. PMID- 11760698 TI - [Phenomenologic complexity of mania]. PMID- 11760699 TI - [How could one conduct self-assessment of mania?]. PMID- 11760700 TI - [The spectre of mania]. PMID- 11760701 TI - [Managing the manic episode in bipolar patients]. PMID- 11760703 TI - Incident analysis. PMID- 11760702 TI - [Predictive effects of anxiety onset in occurrence of postpartum depression in 200 puerperal patients]. PMID- 11760704 TI - Complying with the Health Insurance Portability and Accountability Act. Privacy standards. AB - The Privacy Rule: Limits the use and disclosure of PHI to purposes of treatment, payment, or routine health care operations. Requires covered entities to provide advance notice to the public of its policy governing disclosure of PHI. Requires entities covered by the Standard to secure general client consent to use and to disclose PHI for treatment, payment, or routine health care operations and to obtain specific client authorization to use or to disclose PHI for all other purposes unless the disclosure is specifically permitted without consent or authorization (e.g., a covered entity may disclose PHI to a health care oversight agency such as the Office of the Inspector General without first obtaining client authorization). In certain situations, a covered entity need only obtain client agreement to disclose PHI which may be oral or inferred from the circumstances surrounding the disclosure. For example, a covered entity could disclose PHI to a relative caring for the individual who is the subject of the health information. Expects covered entities to take measures to protect PHI from both inadvertent and deliberate misuse and disclosure. Requires, except in certain circumstances, the amount of PHI disclosed on any occasion to be limited to the minimum necessary to achieve the purpose of the disclosure. Gives individuals more control of their health information by permitting them to review and amend health information pertaining to themselves and to demand an accounting of persons to whom their health information has been disclosed. Establishes terms under which a covered entity may disclose PHI to a business associate. Permits states to maintain state laws that are more stringent than the Privacy Rule. The statute provides for significant civil and criminal penalties for failure to comply with the Standards. Violations are punishable by fines as much as $250,000 and 10 years imprisonment. The HHS, Office of Civil Rights is charged with enforcing the Standards. The HHS is expected to issue a single Enforcement Rule applicable to all three of the HIPAA Administrative Simplification Standards. Many worksite records will not be protected under the HIPAA Privacy Rule because employers are not covered entities and few occupational health professionals meet the criteria of being considered a covered entity. Nevertheless, occupational health professionals need to be knowledgeable about the application of HIPAA in the occupational health care setting. Furthermore, given that the Rule does not preempt state privacy laws that are more stringent than the Standards, occupational health professionals should monitor legislative activity related to privacy in the states in which they practice. To date, Oregon, Texas, and New Jersey have broadened HIPAA's definitions to create more covered entities and services. PMID- 11760705 TI - How does the HIPAA privacy standard affect case management? PMID- 11760706 TI - Bioterrorism. Implications for the occupational and environmental health nurse. AB - 1. Bioterrorism is the intentional release of a biological agent--bacterial, viral, or genetically altered--to instill fear or create chaos, massive casualities, illness, and death in humans, animals, or plants. 2. The threat of bioterrorism is real. Although every community is vulnerable, terrorists seek densely populated, highly visible targets. 3. Occupational and environmental health nurses must to be able to recognize and report signs and symptoms of an early bioweapons outbreak in their workplaces and communities. Only thorough preparedness and planning will result in effective mitigation and treatment. 4. The Bioterrorism Readiness Plan (at http://www.apic.org and http://www.CDC.gov/ncidod/hip) is a template for health care professionals to help plan a realistic response to bioterrorism. It serves as a tool for successful collaboration and communication among all disciplines and public health agencies for the best possible outcomes. PMID- 11760707 TI - Mental health issues in Japanese workers. An update. AB - In this cross sectional study conducted in one city in Japan, psychiatrists were asked to answer self administered questionnaires related to their patients' vital status, constituent family members, employment status, financial support from family, emotional support from family, present state of mental condition, and steps used to help them return to society. The focus of the study was to identify and understand the needs of Japanese workers with mental health problems, and to relate the findings to implications for the workplace. Of the 1,283 male patients reported on in the survey, the greatest proportion (45.1%) suffered from schizophrenia, with the prevalence of this serious illness decreasing with age. One half of the total group worked full or part time, with highest rates of employment among those in their 40s and 50s. The most common jobs were simple physical work or assembly. Workers older than 40 years also were more likely to be responsible for financial support of their families. It is suggested that the occupational health nurse has an important role in providing interventions to help these workers remain productive in the workplace, and thus in society. PMID- 11760708 TI - Management strategies for an aging work force. AB - 1. The demographic shift to an aging population has significant societal and cultural implications that carry over into the workplace. 2. The occupational and environmental health nurse needs to be aware of the risks associated with the aging process including physiological changes of aging, comorbidities and chronic diseases, and psychosocial factors as well as the impact those risks may have on work ability. 3. Health management strategies for an aging worker population include developing an older worker profile, creative job accommodations, and training programs. 4. The occupational and environmental health nursing scope of practice will require significant change for the profession to take a proactive approach to address this workplace transformation. PMID- 11760709 TI - Working with older employees. PMID- 11760710 TI - [Antibiotic therapy in the third millenium]. PMID- 11760711 TI - [Verbum disputabile. Chapter 1. Why and what]. PMID- 11760712 TI - [Effectiveness of St. John's Wort in major depression apparently not indicated]. PMID- 11760714 TI - [It is difficult to research homeopathic remedy provings]. PMID- 11760713 TI - [Mistletoe or not mistletoe is still the question]. PMID- 11760715 TI - [Formic acid and autologous blood in spondylitis]. PMID- 11760716 TI - [Homeopathy for middle ear inflammation: we hope for the best]. PMID- 11760717 TI - [Are homeopathic studies better-fated in India?]. PMID- 11760718 TI - [Otomycosis]. PMID- 11760719 TI - [Verbum disputabile. Chapter 2. Democritization of ethics in medicine]. PMID- 11760720 TI - Targeted Therapies in the Treatment of Breast Cancer. Proceedings of a meeting. Kailua-Kona, Hawaii, July 19-23, 2000. PMID- 11760721 TI - Heavy cigarette smoking and RA. PMID- 11760722 TI - Rheumatoid arthritis associated with ulcerative colitis. PMID- 11760723 TI - Intramuscular methotrexate in inflammatory rheumatic disease. PMID- 11760724 TI - Epidemiology of vasculitis in Europe. PMID- 11760725 TI - Anti-U3 snRNP antibodies in localised scleroderma. PMID- 11760726 TI - Telomerase activity in peripheral blood mononuclear cells from patients with SLE. PMID- 11760727 TI - Treatment of ankylosing spondylitis with infliximab. PMID- 11760729 TI - Current world literature. Paediatric urology. PMID- 11760728 TI - Retrocalcaneal bursitis in polymyalgia rheumatica. PMID- 11760730 TI - Current world literature. Andrology, sexual dysfunction, infertility. PMID- 11760732 TI - [Left-handed in a right-handed world. Left behind?]. PMID- 11760731 TI - Normative studies with the Scale for Interpersonal Behaviour (SIB): II. US students. A cross-cultural comparison with Dutch data. AB - The Scale for Interpersonal Behaviour (SIB), a multidimensional, self-report measure of state assertiveness, was administered to a nationwide sample of 2375 undergraduates enrolled at 11 colleges and universities across the USA. The SIB was developed in the Netherlands for the independent assessment of both distress associated with self-assertion in a variety of social situations and the likelihood of engaging in a specific assertive response. This is done with four factorially-derived, first-order dimensions: (i) Display of negative feelings (Negative assertion); (ii) Expression of and dealing with personal limitations; (iii) Initiating assertiveness; and (iv) Praising others and the ability to deal with compliments/praise of others (Positive assertion). The present study was designed to determine the cross-national invariance of the original Dutch factors and the construct validity of the corresponding dimensions. It also set out to develop norms for a nationwide sample of US students. The results provide further support for the reliability, factorial and construct validity of the SIB. Compared to their Dutch equivalents, US students had meaningfully higher distress in assertiveness scores on all SIB scales (medium to large effect sizes), whereas differences on the performance scales reflected small effect sizes. The cross national differences in distress scores were hypothesized to have originated from the American culture being more socially demanding with respect to interpersonal competence than the Dutch, and from the perceived threats and related cognitive appraisals that are associated with such demands. PMID- 11760733 TI - Aptitude for osteopathic training. 1939. PMID- 11760734 TI - Osteopathic education looks ahead. 1948. PMID- 11760735 TI - Peripheral primitive neuroectodermal tumor: challenge for multimodal treatment. AB - The primitive neuroectodermal tumor (PNET) is an extremely aggressive soft tissue neoplasm that occurs in children and adolescents. We retrospectively reviewed our therapeutic experience with a multidisciplinary approach, combining surgery, chemotherapy, and radiation therapy. Treatment of PNET was carried out in compliance with the soft tissue protocol (CWS) from the German Society of Pediatric Oncology. Biopsy-proven diagnosis was followed by chemotherapy, which in all cases led to partial remission, allowing excision of the remainder of the tumor without mutilation. After excision, irradiation of the tumor site and two further sequences of chemotherapy were performed. When PNET of the paravertebral region caused symptoms of paralysis and immediate surgery was required, postoperative chemotherapy, a second-look operation, and irradiation were undertaken. Between 1986 and 1998 we treated 13 patients (median age 15 years). In five patients the PNET originated from the chest wall and in eight patients from the paravertebral and retroperitoneal region. Five patients died after 20 months on average, and the remaining eight patients are in full remission after 7, 16, 46, 55, 70, 74, 75, and 115 months, respectively. Close cooperation between surgeons and their pediatric and radiotherapy colleagues is obligatory when treating PNET. Chemotherapy as the first stage is mandatory to avoid a mutilating surgical procedure and intraoperative tumor cell dissemination. PMID- 11760736 TI - Is timing of death from tumor recurrence predictable after curative resection for gastric cancer? AB - It is still difficult to predict whether cancer in patients who undergo curative gastrectomy for gastric cancer will recur and when they will die of recurrence. This study clarified predictive factors related to timing of death from tumor recurrence. A multivariate analysis was used to assess the dependence of death on postoperative tumor recurrence and were the dependence of the timing of death on tumor recurrence. Patients were divided into two groups according to the timing of death: those who died of tumor recurrence less than 2 years after surgery and those who died more than 2 years after surgery. Depth of cancer invasion, regional lymph node metastasis, and tumor size were independently correlated with tumor recurrence after curative gastrectomy. Onlv the depth of cancer invasion independently correlated with the timing of death due to tumor recurrence. It might be possible to predict the timing of death from tumor recurrence by the depth of cancer invasion into the gastric wall. PMID- 11760737 TI - Barostat examination of proximal site of the anastomosis in patients with rectal cancer after low anterior resection. AB - Patients who have undergone low anterior resection (LAR) of the rectum for cancer show symptoms of urgency and frequency of defecation after meals. The cause of these symptoms is unclear. It was hypothesized that the functional disorder of the proximal site of the anastomosis after low anterior resection of the rectum often leads to the symptoms and that the 5-HT3 receptor antagonist reduces postprandial colonic contractions. The aim of this study was to assess colon contractions of the proximal site of the anastomosis and the effects of the 5-HT3 receptor antagonist on the contractions. We evaluated 37 patients who had undergone LARs, 17 with high stool frequency (more than four times per day) and 20 with normal stool frequency. In the first part of the study, basal tone, compliance of the proximal site of the anastomosis, and response to a meal (300 kcal) were recorded with a barostat in all patients. In the second part of the study the effects of the 5-HT3 receptor antagonist on contractions of the proximal site of the anastomosis after ingesting a meal was evaluated. Seven healthy controls were also studied for descending colonic tone with a barostat after a meal. Basal barostat balloon volumes showed only small variations in the two post-LAR groups. Compliance of the proximal site of the anastomosis was similar in the two groups. Meal ingestion stimulated contractions of the proximal site of the anastomosis. In patients with high stool frequency the proximal site of the anastomosis contracted earlier than in those with normal stool frequency after a meal. The descending colonic tone of healthy controls did not change after a meal. The 5-HT3 receptor antagonist inhibited postprandial contractions of the proximal site of the anastomosis after LAR. These observations lend support to the idea that gastrocolonic reflex increases in patients who have undergone LAR, leading to high stool frequency. Furthermore, the 5-HT3 receptor antagonist may alleviate the symptoms of urgency and the frequency of defecation. PMID- 11760738 TI - Surgeons who contributed to the enlightenment of Japanese medicine. AB - Until the sixteenth century internal medicine, primarily Chinese medicine, had been predominant in Japan. From 1639, under the national seclusion policy of the Tokugawa Shogunate, Japan's doors were closed to the West; and Japan had no trade relations with any countries except China and Holland. Only in Nagasaki, where a Dutch settlement was located, were Japanese able to learn about Western culture and Western medicine. Through the medical education and services provided by Philipp Franz von Siebold, Western surgery was introduced to Japan. In 1854 Japan was opened to the world, and many German physicians were invited to provide medical education in Japan. The German medical education system continued until about 1950. After World War II, Japanese medical education was reformed, and several medical professors from U.S. universities were sent to Japan. One was Charles G. Johnston of Wayne State University. Thanks to the efforts of these visiting American professors, many young Japanese doctors were sent to the United States to study surgery, anesthesia, and the like. These doctors later became the leaders of medical education in Japan. The guidance and friendship of these foreign doctors had a profound effect on the progress and advancement of modern Japanese medicine. PMID- 11760739 TI - Selection of nonoperative management candidates. AB - The liver and spleen are the most commonly injured intraabdominal organs and comprise most of the injuries to the solid viscera during blunt abdominal injury. The contrast-enhanced computed tomography (CT) scan has emerged as an accurate, safe diagnostic tool for blunt torso trauma, making nonoperative management of even severe injury to the liver and spleen possible. This review concentrates on the trends, patient selection criteria, and some of the risks of nonoperative management of hemodynamically stable patients with blunt liver and spleen injury. PMID- 11760740 TI - Factors of failure for nonoperative management of blunt liver and splenic injuries. AB - A review of the literature describing the management of hepatic and splenic injuries indicates that as many as 67% of exploratory celiotomies for blunt trauma are reported as nontherapeutic. Avoiding unnecessary surgery through nonoperative management offers an attractive alternative. Nonetheless, nonoperative management should not be considered unless the patient meets the following criteria: (1) hemodynamic stability, with or without minimal fluid resuscitation; (2) no demonstrable peritoneal signs on abdominal examination; and (3) the absence on computed tomography (CT) scan of any intraperitoneal or retroperitoneal injuries that require operative intervention. Although a patient may meet these criteria, several additional factors can serve as predictors of failure of nonoperative management. Such predictors among patients with hepatic injuries are hemodynamic instability, liver injury of American Association for the Surgery of Trauma grades IV and V (especially when accompanied by hemodynamic instability), and pooling of contrast on CT scan. Formerly thought to be a predictor of failure of nonoperative management, periportal tracking has not been cited as such in recent reports of hepatic injuries. Among patients with blunt splenic injuries, such predictors include hemodynamic instability, injury of grade IV or higher, large associated hemoperitoneum, and contrast blush on CT scan. Although preexisting splenic disease and age older than 55 years have traditionally been considered predictors of failure, recent reports have shown that these characteristics do not appear to be associated with an increased need for surgical intervention. PMID- 11760741 TI - Computed tomography, angiography, and endoscopic retrograde cholangiopancreatography in the nonoperative management of hepatic and splenic trauma. AB - There is a marked trend toward nonoperative management of abdominal trauma. This has been possible thanks to the advances in imaging and interventional techniques. In this work we review in which way computed tomography (CT) abdominal scans, angiography, and endoscopic retrograde cholangiopancreatography (ERCP) can guide the nonoperative management of hepatic and splenic trauma. The CT abdominal scan with intravenous contrast is the "departure imaging" of choice for the nonoperative management of hepatic and splenic trauma in the hemodynamically stable patient. It is the most accurate test for detecting, defining, and characterizing these injuries, the associated hemoperitoneum, and other abdominal abnormalities (the hollow viscus injuries missed on the CT scan were detected by clinical parameters and had no negative consequences in the outcome). It has an accuracy of more than 95% for these injuries, but CT grading alone cannot decide which patient can be treated conservatively and which patient requires surgery. Its usefulness for follow-up seems challenging. Angiography can be therapeutic, thereby avoiding surgery (some report that angiography can be performed even in patients with active bleeding as damage control); if vessel injury, active bleeding or hemobilia are suspected on the basis of a CT scan in a stable patient, angiography should be carried out. ERCP should be performed in patients with suspected injury to the biliary tree, even with normal iminodiacetic acid radionuclide scanning (HIDA) if symptoms persist. A biliary stent can be placed. Indications for angiography and ERCP remain unclear. PMID- 11760743 TI - Nonoperative treatment of blunt splenic injury. AB - A spleen-preserving program was implemented at the author's institution during the mid-1980s using a five-part injury-grading scale that is similar and comparable to the AAST classification. Since that time, all patients with splenic injuries admitted to the Department of Surgery at the Karl-Franzens University Hospital in Graz, a level I trauma center, have been prospectively evaluated with respect to splenic preservation. Analysis of the relation of the severity of organ injury to the use of nonoperative management showed that degree I or II injuries were treated nonoperatively, whereas degree III and IV injuries were usually treated with adhesives, partial resection, or mesh splenorrhaphy; only degree V injuries almost always required splenectomy. With increasing experience in nonoperative management of splenic injuries the initial criteria have become less rigid, and there is now a tendency to attempt it in patients who formerly would have undergone surgery. PMID- 11760742 TI - Current status of nonoperative management of liver injuries. AB - The successful use of nonoperative management of liver injuries requires a hemodynamically stable patient and early access to computed tomography (CT). Extensive intraperitoneal blood and extravasation of contrast on CT predict potential clinical failures. The CT appearance of the liver injury has poor correlation with clinical outcome. Angiographic embolization complements nonoperative management in the stable patient with an ongoing blood requirement. The follow-up CT scan is not required provided the hematocrit and the patient's clinical status remain stable. Common errors in nonoperative management include attributing evidence of blood loss to nonhepatic sources and continuing transfusions in anticipation that the bleeding will stop without intervention. PMID- 11760744 TI - Information age technologies for surgeons: overview. AB - This overview summarizes the revolutionary changes that are occurring in medicine today and looks beyond medicine to the other disciplines of science that contribute to the overall revolution of the Information Age. The concept of "information equivalent," representing real objects within a computer as information, is explained. The application of today's emerging information technologies is divided into the components of patient care--diagnosis, consultation, treatment, and education--and illustrations are given of how information sciences are changing the practice of surgery. PMID- 11760745 TI - Telesensor integrated circuits. AB - Progress in personal computing has recently permitted small research programs to design and simulate application-specific integrated circuits (ASICs). Inexpensive fabrication of silicon chips can then be obtained using chip foundries, and quite complex circuits can be greatly reduced in size with an accompanying increase in certain performance characteristics. Within the past 5 years it has also become possible to design ASICs which can transmit and receive radio signals and which thus may be employed in applications in which wired connections for input and output of signals are not practicable. We are currently developing research-grade prototype ASICs for the monitoring of human vital signs. In this case one or more sensors placed on an ASIC provides a signal to be transmitted a distance of 2-3 meters to a receiver/display unit. The use of ASIC telesensors provides the possibility of wireless monitoring, including long-term monitoring, with inexpensive and unencumbering devices. Their self-contained nature permits a number of potential uses in future biomedical applications as new sensors are devised which are amenable to deployment on silicon. PMID- 11760746 TI - Image display technology and image processing. AB - Significant developments in video imaging have taken place but further progress is needed to provide images with the right characteristics for optimal interpretation by the operator. The nature and location of the image display in relation to the surgeon and operating field are also important in facilitating image-guided surgery/interventions, and several new technologies are being explored. In the diagnostic field, virtual reality surface anatomical and internal luminal rendering has opened a new chapter in diagnosis, screening, and treatment planning, the potential of which is only just being realized. PMID- 11760747 TI - Image acquisition: ultrasound, computed tomography, and magnetic resonance imaging. AB - As the transition toward total digital image acquisition continues, radiology is transcending the current standard of two-dimensional (2-D) cross-sectional anatomic imaging to more complex models. Among these are three-dimensional (3-D) anatomic images, constructed either from a synthesis of traditional 2-D data sets, or directly from volumetrically acquired data. However, current trends are moving beyond mere anatomic imaging to include physiological data once mainly obtained via nuclear medicine. Recent magnetic resonance pulse sequences, in addition to Doppler and harmonic ultrasound methods, are providing insight into blood flow, oxygenation, and metabolite concentrations non-invasively. Through image registration techniques, these data (even from differing modalities) are being assembled into 2-D and 3-D "fusion" images that promise to revolutionize diagnosis. Furthermore, with improvements in miniaturization, reliability, speed, built-in intelligence, and ease of use, these new developments are finding their way into use by nonspecialists. For instance, a new hand-held ultrasound unit will likely become a common tool among emergency medical teams, military medical teams, and in NASA's manned space program. Portable computed tomography (CT) scanners are already being used in the operating room. The increasing sophistication of imaging instruments will bring about a complementary increase in ease of use for both scanning and data interpretation, bringing diagnostic imaging and therapeutic capabilities closer to the patient, rather than the converse. PMID- 11760748 TI - Telementoring and teleproctoring. AB - Telemedicine has previously been defined as "live two-way interactive video communication between a physician and a patient and/or another physician, where all participants are able to see and hear one another much like a face to face encounter." This concept has gained recent notoriety because of the great advances in telecommunications and the potential future increased cost effectiveness associated with its utilization. We have developed a telementoring deployment protocol that can be effectively used to introduce a student to telementoring processes. The strict protocol uses military commands to facilitate smooth information transfer. The use of a concept called tactical information deployment provides the surgeon with rapid access to reference information in the operating suite. Multimedia interactive CD-ROMs, with digitized movie clips, illustrations, sound bits, and the latest academic review of the literature arm the surgeon with a database that establishes an unprecedented clinical adaptive capability (CAC). The availability of this information is invaluable to surgeons in their initial advanced laparoscopic procedural efforts. Telementoring simulator opportunities are included to acclimate the participant to the process. If the process seems comprehensive, it is meant to be. This is a high-risk situation, and a patient's welfare is on the line. If this concept is to reach its maximal healthcare delivery potential, responsible and academically credible training programs should be established with directional guidelines. PMID- 11760749 TI - Telemedicine, the Internet, and world wide web: overview, current status, and relevance to surgeons. AB - The Information Age has made profound changes in society and is slowly entering the healthcare field. Some of the most important areas are telemedicine, the Internet, and the world wide web (www). Millions of physicians, healthcare providers, and patients are accessing the web daily for patient information, consultation, and distant learning. Telemedicine is beginning to enter the mainstream of health care after decades of demonstration projects. There are many issues which have been raised, such as access to the information, the security of the information, and the quality of the content on the web. While telemedicine is beginning to Hower, there are numerous barriers that prevent its rapid implementation, such as licensure, reimbursement, liability, quality of service, and technical issues. In spite of the numerous challenges, telemedicine over the Internet was practiced in one of the most remote areas of the world--Mt. Everest- demonstrating that it is possible to utilize all the latest healthcare telecommunications tools in even the most extreme of settings. PMID- 11760750 TI - Tissue engineering and its potential impact on surgery. AB - The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in healthcare. Current treatment modalities include transplantation of organs, surgical reconstruction, use of mechanical devices, or supplementation of metabolic products. A new field, tissue engineering, applies the principles and methods of engineering, material science, and cell and molecular biology toward the development of viable substitutes which restore, maintain, or improve the function of human tissues. In this review, we outline the opportunities and challenges of this emerging interdisciplinary field and its attempts to provide solutions to tissue creation and repair. Within this context, we present our experience using the basic tools of tissue engineering to guide regeneration of diverse tissues that include the liver, small intestine, cardiovascular structures, nerve, and cartilage. And in addition, we discuss the necessity of finding new strategies to achieve vascularization of complex tissues for transplant and present our approaches utilizing MicroElectroMechanical Systems (MEMS) technology and three-dimensional printing. PMID- 11760751 TI - Feasibility of robotic laparoscopic surgery: 146 cases. AB - Theoretically, in laparoscopic surgery, a computer interface in command of a mechanical system (robot) allows the surgeon: (1) to recover a number a number of lost degrees of freedom, thanks to intraabdominal articulations; (2) to obtain better visual control of instrument manipulation, thanks to three-dimensional vision; (3) to modulate the amplitude of surgical motions by downscaling and stabilization; (4) to work at a distance from the patient. These advances improve the quality of surgical tasks in a perfect ergonomic position. The purpose of this paper is to evaluate the feasibility of utilizing a robot in laparoscopic surgery. The first robot-assisted procedure in humans was performed in March 1997 by our team. One hundred forty-six patients underwent robot-assisted laparoscopic surgery. Between March 1997 and February 2001 a nonconsecutive series was performed of 39 antireflux procedures, 48 cholecystectomies, 28 tubal reanastomoses, 10 gastroplasties for obesity, 3 inguinal hernias, 3 intrarectal procedures, 2 hysterectomies, 2 cardiac procedures, 2 prostactectomies, 2 arteriovenous fistulas, 1 lumbar sympathectomy, 1 appendectomy, 1 laryngeal exploration, 1 varicocele ligation, 1 endometriosis cure, 1 neosalpingostomy, 1 deferent canal. The robot (Da Vinci system, Intuitive Surgical, Mountain View, CA), consists of a console and a cart with three articulated robot arms. The surgeon sits in front of the console, manipulating joysticklike handles while observing the operative field through binoculars that provide a three-dimensional picture. This computer is capable of modulating these data by eliminating physiologic tremor and by downscaling the amplitude of motions by a factor 5 or 3 to one. This study has demonstrated the feasibility of several laparoscopic robotic procedures. There is no morbidity related to the system. Operating time and the hospital stay were within acceptable limits. The system seems most beneficial in intra-abdominal microsurgery or for manipulations in a very small space. Optimized ergonomics and increased mobility of the instrument tips are beneficial in many steps of abdominal surgical procedures. PMID- 11760752 TI - Objective psychomotor skills assessment of experienced, junior, and novice laparoscopists with virtual reality. AB - Objective assessment of psychomotor skills in surgery is now a priority; however, this assessment is difficult to achieve because of measurement difficulties associated with the reliability and validity of assessing surgical skills in vivo and in the laboratory. In this study virtual reality (VR) was used to overcome these problems in the objective psychomotor assessment of senior, junior, and novice laparoscopists. Twelve experienced laparoscopic surgeons (performed >50 Minimal Access Surgery (MAS) procedures), 12 inexperienced laparoscopic surgeons (<10 MAS procedures), and 12 laparoscopic novices (no MAS procedures) participated in the study. Each subject completed all six tasks of the Minimally Invasive Surgical Trainer; Virtual Reality (MIST VR). In comparison to the other groups, experienced laparoscopic surgeons performed the tasks significantly (p < 0.01) faster, had a lower error rate, were more economic in their movement of surgical instruments and in the use of diathermy. As a group they also showed greater consistency in their performance. MIST VR distinguished between the three groups of laparoscopists. VR provides a useful objective assessment tool for evaluating psychomotor skills for laparoscopic surgery. PMID- 11760753 TI - Surgical education and surgical simulation. AB - The science of virtual reality provides an entirely new opportunity in the area of simulation of surgical skills using computers for training, evaluation, and eventually certification. A taxonomy of the types of simulators is proposed based upon the level of complexity of the task which is being simulated. These tasks are precision placement, simple manipulation, complex manipulation, and integrated procedure. Representative simulators in each category are illustrated and discussed in the context of their contribution to the education and training of a surgeon. The importance of a curriculum is to give content to the role of simulators as another advanced tool for education. Simulators must be integrated into a comprehensive curriculum and not considered as a stand-alone system. The current accomplishments as well as challenges are discussed. PMID- 11760754 TI - Teleeducation in surgery: European Institute for Telesurgery experience. AB - The information age is revolutionizing the practice and education of surgery. The use of video-conference systems through Integrated Service Digital Network (ISDN) teletransmission connects surgeons around the world without the limits of distance. Teleeducation, teleteaching, teletraining, telementoring, and teleaccreditation have been clearly demonstrated and are now common practice. Pre and perioperative surgical advice may be obtained from expert networks. Patient data can be reconstructed as virtual tridimensional images analyzed by computers, and the surgical procedure can be simulated to obtain an optimal surgical decision. Finally, the use of the Internet will provide access to this information, whenever and wherever necessary, through dedicated websites. It remains to be adequately demonstrated that these means will allow improvement in patient care. PMID- 11760755 TI - [Rumors, fear or epidemy? The bubonic plague of 1913-1914 in the Atlantic coast of Columbia]. AB - By the end of the 1800s, international trade and steam navigation made way for the third bubonic plague pandemy, which started in China in 1891 and reached America in 1898. This calamity apparently arrived in Columbia's coast between 1913 and 1915, during the apex of Pasteur medicine. The deficiencies of Columbian public scientific and sanitary apparat, concerning the emerging bacteriology and epidemiology, prevented the government and the medical body from reacting against the fear and rumor of epidemy, which negatively affected the trade. The authorities were also unable to fight this problem with adequate diagnosis, enferms treatment, urban sanitation, and isolation of infected places. These difficulties led to a confrontation between the government and the medical body, inciting an argument about the existence of the plague. This discussion was settled by the North American official medicine that, in its verdict, gave preference to the commercial interests of the United States, ignoring the sanitary urgencies of the Columbian Atlantic coast. PMID- 11760756 TI - [Brazilian medical literature about the white plague: 1870-1940]. AB - The Darwinian theories compound the paradigm adopted by the physicians in Southern United States, when they turned to the subject of the differences in morbidity and mortality among the races after abolition. These physicians engaged in thoughts about the health crisis that assaulted the African-American population on that region. The Brazilian physicians, on the other hand, would not try to understand or explain the health crisis that overtook the population descended from Africans on their country. Actually, not a single Brazilian medical journal, since the end of abolition to the 1930s, published an article where a physician indicated the morbidity and mortality of his negro patients, or of negroes in general, as caused by any source related to the racial paradigm. The psychiatrists and eugenicist doctors were exceptions. PMID- 11760757 TI - [Notes for a history of health: document sources of Parana]. PMID- 11760758 TI - [Over the cuckoo's nest: memories of a former president of Funacao Oswaldo Cruz]. PMID- 11760759 TI - Occupational injury and illness recording and reporting requirements. Final rule. AB - The Occupational Safety and Health Administration (OSHA) is delaying the effective date of three provisions of the Occupational Injury and Illness Recording and Reporting Requirements rule published January 19, 2001 (66 FR 5916 6135) and is establishing interim criteria for recording cases of work-related hearing loss. The provisions being delayed are sections 1904.10 (a) and (b), which specify recording criteria for cases involving occupational hearing loss, section 1904.12, which defines "musculoskeletal disorder (MSD)" and requires employers to check the MSD column on the OSHA Log if an employee experiences a work-related musculoskeletal disorder, and section 1904.29(b)(7)(vi), which states that MSDs are not considered privacy concern cases. The effective date of these provisions is delayed from January 1, 2002 until January 1, 2003. OSHA will continue to evaluate sections 1904.10 and 1904.12 over the next year. OSHA is also adding a new paragraph(c) to section 1904.10, establishing criteria for recording cases of work-related hearing loss during calendar year 2002. Section 1904.10(c) codifies the enforcement policy in effect since 1991, under which employers must record work related shifts in hearing of an average of 25 dB or more at 2000, 3000 and 4000 hertz in either ear. PMID- 11760760 TI - Infant mortality. PMID- 11760761 TI - Medicare program; revisions to payment policies and five-year review of and adjustments to the relative value units under the physician fee schedule for calendar year 2002. Final rule with comment period. AB - This final rule with comment period makes several changes affecting Medicare Part B payment. The changes affect: refinement of resource-based practice expense relative value units (RVUs); services and supplies incident to a physician's professional service;anesthesia base unit variations;recognition of CPT tracking codes; and nurse practitioners, physician assistants, and clinical nurse specialists performing screening sigmoidoscopies. It also addresses comments received on the June 8, 2001 proposed notice for the 5-year review of work RVUs and finalizes these work RVUs. In addition,we acknowledge comments received on our request for information on our policy for CPT modifier 62 that is used to report the work of co-surgeons. The rule also updates the list of certain services subject to the physician self-referral prohibitions to reflect changes to CPT codes and Healthcare Common Procedure Coding System codes effective January 1, 2002. These refinements and changes will ensure that our payment systems are updated to reflect changes in medical practice and the relative value of services. The Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000 modernizes the mammography screening benefit and authorizes payment under the physician fee schedule effective January 1, 2002; provides for biennial screening pelvic examinations for certain beneficiaries effective July 1, 2001; provides for annual glaucoma screenings for high-risk beneficiaries effective January 1,2002; expands coverage for screening colonoscopies to all beneficiaries effective July 1, 2001; establishes coverage for medical nutrition therapy services for certain beneficiaries effective January 1, 2002; expands payment for telehealth services effective October 1, 2001; requires certain Indian Health Service providers to be paid for some services under the physician fee schedule effective July 1, 2001; and revises the payment for certain physician pathology services effective January 1, 2001. This final rule will conform our regulations to reflect these statutory provisions. In addition, we are finalizing the calendar year (CY) 2001 interim RVUs and are issuing interim RVUs for new and revised procedure codes for calendar year (CY) 2002. As required by the statute, we are announcing that the physician fee schedule update for CY2002 is -4.8 percent, the initial estimate of the Sustainable Growth Rate (SGR) for CY 2002 is 5.6 percent, and the conversion factor for CY 2002 is $36.1992. PMID- 11760762 TI - Health status indicators: definitions and national data. AB - In July 1991 the Centers for Disease Control (CDC) released a set of 18 health status indicators and encouraged their use by federal, State, and local health agencies. The indicators were developed in response to Objective 22.1 of Healthy People 2000 through a consensus process described in a previous Statistical Notes. This article recommends detailed definitions, suggests national data sources, and provides national baseline data for each indicator. PMID- 11760763 TI - Issues related to monitoring the Year 2000 objectives. PMID- 11760764 TI - Medicare program--prospective payment system for hospital outpatient services: criteria for establishing additional pass-through categories for medical devices. Interim final rule with comment period. AB - This interim final rule with comment period sets forth the criteria the Secretary will use to establish new categories of medical devices eligible for transitional pass-through payments under Medicare's hospital outpatient prospective payment system. PMID- 11760765 TI - Medicare program; announcement of the calendar year 2002 conversion factor for the hospital outpatient prospective payment system and a pro rata reduction on transitional pass-through payments. Final rule. AB - This final rule announces the Medicare hospital outpatient prospective payment system conversion factor for calendar year (CY) 2002. In addition, it describes the Secretary's estimate of the total amount of transitional pass-through payments for CY 2002 and the implementation of a uniform reduction in each of the pass-through payments for that year. PMID- 11760766 TI - Dispensing of controlled substances to assist suicide. Interpretive rule. AB - For the reasons provided in the memorandum set forth below, the Attorney General has determined that assisting suicide is not a "legitimate medical purpose" within the meaning of 21 CFR 1306.04 (2001), and that prescribing, dispensing, or administering federally controlled substances to assist suicide violates the Controlled Substances Act. Such conduct by a physician registered to dispense controlled substances may "render his registration . . . inconsistent with the public interest" and therefore subject to possible suspension or revocation under 21 U.S.C. 824(a)(4). The Attorney General's conclusion applies regardless of whether state law authorizes or permits such conduct by practitioners or others and regardless of the condition of the person whose suicide is assisted. The Attorney General recognizes, however, that pain management is a legitimate medical purpose justifying a physician's dispensing of controlled substances. Finally, the Attorney General's determination makes no change in the current standards and practices of the DEA in any State other than Oregon. PMID- 11760767 TI - Written and oral information or statements affecting entitlement to benefits. Final rule. AB - This document amends the Department of Veterans Affairs (VA) adjudication regulations to eliminate the requirement that beneficiaries advise VA of changes affecting entitlement to benefits in writing. This allows VA to increase or decrease benefit payments based on information submitted orally or by e-mail, facsimile, or other electronic means and makes it easier for beneficiaries to submit information that they must provide. This document also amends our notice requirements to allow VA to reduce or terminate benefit payments based on information reported orally without issuing a 60-day advance notice, but only under certain conditions that ensure that claimants are not deprived of benefits without adequate notice. This will reduce the amounts of any over payments created by these actions. PMID- 11760768 TI - Extension of the presumptive period for compensation for Gulf War veterans' undiagnosed illnesses. Interim final rule with request for comments. AB - The Department of Veterans Affairs (VA) is amending its adjudication regulations regarding compensation for disabilities resulting from undiagnosed illnesses suffered by Persian Gulf War veterans. This amendment is necessary to extend the period within which such disabilities must become manifest to a compensable degree in order for entitlement for compensation to be established. The intended effect of this amendment is to ensure that veterans with compensable disabilities due to undiagnosed illnesses that may be related to active service in the Southwest Asia theater of operations during the Persian Gulf War may qualify for benefits. PMID- 11760769 TI - A model for types and levels of human interaction with automation. AB - Technical developments in computer hardware and software now make it possible to introduce automation into virtually all aspects of human-machine systems. Given these technical capabilities, which system functions should be automated and to what extent? We outline a model for types and levels of automation that provides a framework and an objective basis for making such choices. Appropriate selection is important because automation does not merely supplant but changes human activity and can impose new coordination demands on the human operator. We propose that automation can be applied to four broad classes of functions: 1) information acquisition; 2) information analysis; 3) decision and action selection; and 4) action implementation. Within each of these types, automation can be applied across a continuum of levels from low to high, i.e., from fully manual to fully automatic. A particular system can involve automation of all four types at different levels. The human performance consequences of particular types and levels of automation constitute primary evaluative criteria for automation design using our model. Secondary evaluative criteria include automation reliability and the costs of decision/action consequences, among others. Examples of recommended types and levels of automation are provided to illustrate the application of the model to automation design. PMID- 11760770 TI - Preoxygenation time versus decompression sickness incidence. AB - Preoxygenation, breathing 100% oxygen prior to decompression, has been used for well over half of this century to reduce decompression sickness (DCS) incidence. Duration of preoxygenation has been reported to be inversely related to subsequent DCS incidence. A direct comparison of DCS incidence at 30,000 ft versus preoxygenation time is needed to allow better-informed decisions regarding the cost vs. benefit of increasing preoxygenation time to prevent DCS. To obtain such a comparison, we accomplished a retrospective study of exposures to 30,000 ft (226 mm Hg; 4.37 psia) while performing mild exercise. The 86 male exposures were preceded by preoxygenation times of one to four hours. Venous gas emboli (VGE) and DCS symptom development were monitored and recorded. Although more protection was demonstrated with increasing preoxygenation time, the cost-to benefit ratio also increases with each additional increment of preoxygenation time. The diminishing return of increasing preoxygenation to reduce DCS would eventually impact mission planning and crew duty limitations. Alteration in the physiology of denitrogenation, such as inclusion of exercise during preoxygenation, may provide better and more cost-effective DCS protection than simply increasing preoxygenation time. PMID- 11760771 TI - Field intercomparison of a novel optical sensor for formaldehyde quantification. AB - A one-week in situ intercomparison campaign was completed on the Rice University campus for measuring HCHO using three different techniques, including a novel optical sensor based on difference frequency generation (DFG) operating at room temperature. Two chemical derivatization methods, 2,4-dinitrophenylhydrazine (DNPH) and o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA), were deployed during the daylight hours for three- to four-hour time-integrated samples. A real time optical sensor based on laser absorption spectroscopy was operated simultaneously, including nighttime hours. This tunable spectroscopic source based on difference frequency mixing of two fiber-amplified diode lasers in periodically poled LiNb03 (PPLN) was operated at 3.5315 micrometers (2831.64 cm 1) to access a strong HCHO ro-vibrational transition free of interferences from other species. The results showed a bias of -1.7 and -1.2 ppbv and a gross error of 2.6 and 1.5 ppbv for DNPH and PFBHA measurements, respectively, compared with DFG measurements. These results validate the DFG sensor for time-resolved measurements of HCHO in urban areas. PMID- 11760773 TI - [Imminent strenghtenment of the protection of medical relics and collections]. PMID- 11760774 TI - [Clinical medicine of the western medicine in the 18th century]. AB - The 18th century is an important turning point not only in human history, but also in medical history. G. B. Morgagni was an Italian who founded the organic pathology in the 18th century, which was a bridge between basic medicine and clinical medicine of western medicine. H. Boerhaave called for "paying attention to the development of clinical medicine", and under this situation, western clinical medicine was attached importance and developed again in the 18th century. However, at the same time, the mechanical materialism was also infiltrated into western clinical medicine. PMID- 11760772 TI - Factors enhancing Agrobacterium tumefaciens-mediated gene transfer in peanut (Arachis hypogaea L.). AB - Parameters enhancing Agrobacterium-mediated transfer of foreign genes to peanut (Arachis hypogaea L.) cells were investigated. An intron-containing beta glucuronidase uidA (gusA) gene under the transcriptional control of CaMV 35S promoter served as a reporter. Transformation frequency was evaluated by scoring the number of sectors expressing GUS activity on leaf and epicotyl explants. The 'Valencia Select' market type cv. New Mexico was more amenable to Agrobacterium transformation than the 'runner' market type cultivars tested (Florunner, Georgia Runner, Sunrunner, or South Runner). The disarmed Agrobacterium tumefaciens strain EHA101 was superior in facilitating the transfer of uidA gene to peanut cells compared to the disarmed strain C58. Rinsing of explants in half-strength Murashige-Skoog (MS) media prior to infection by Agrobacterium significantly increased the transformation efficiency. The use of cocultivation media containing high auxin [1.0 or 2.5 mg/l (4.53 micromolar or 11.31 micromolar) 2,4 D] and low cytokinin [0.25 or 0.5 mg/l (1.0 micromolar or 2.0 micromolar) BA] promoted higher transformation than either hormone-free or thidiazuron-containing medium. The polarity of the epicotyl during cocultivation was important; explants incubated in an inverted (vertically) manner followed by a vertically upright position resulted in improved transformation and shoot regeneration frequencies. Preculture of explants in MS basal medium or with 2.5 mg thidiazuron per l prior to infection drastically decreased the number of transformed zones. The optimized protocol was used to obtain transient transformation frequencies ranging from 12% to 36% for leaf explants, 15% to 42% for epicotyls. Initial evidence of transformation was obtained by polymerase chain reaction and subsequently confirmed by Southern analysis of regenerated plants. PMID- 11760775 TI - [Humoralism and its influence on western medicine]. AB - As the cornerstone of the ancient theories in the west, humoralism had been a dominative theory in medicine from the ancient Greek time to the 19th century, prior to the birth of the bacterial theory of disease. As a theory of holistic medicine in the west in ancient period, humoralism was similar to traditional Chinese medicine in its viewpoints of health and disease. Therefore, the review of its origin, cardinal principles and its evolution, is not only significant in the correct understanding of ancient western medicine and its appraisal, but also for the interpretation of traditional Chinese medicine as a reference. PMID- 11760776 TI - The basis for drug treatment of the overactive bladder. AB - The normal bladder functions, storage and elimination of urine, are dependent on neural circuits in the brain and spinal cord that coordinate the activity of the detrusor and that of the smooth and striated muscles of the outflow region. Disturbances at different levels may cause the overactive bladder (OAB) syndrome, characterized by urge, frequency and urge incontinence. Knowledge about the mechanisms controlling both normal and abnormal micturition is mandatory for the detection of targets for pharmacological intervention. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. Traditionally, drugs for treatment o PMID- 11760777 TI - Which muscarinic receptor is important in the bladder? AB - Antimuscarinic agents are the most widely used therapy for urge incontinence, but have side effects such as constipation, tachycardia and dry mouth, resulting from a lack of selectivity for the bladder. M2 receptors are the predominant cholinoceptors present in urinary bladder, but mainly the minor population of M3 receptors mediate its contraction. M2 receptors modulate detrusor contraction by several mechanisms, and may contribute more to contraction of the bladder in pathological states such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2 or M4 receptors and prejunctional facilitatory muscarinic Ml receptors in the bladder have all been reported. In clinical studies, tolterodine, a non-selective muscarinic antagonist, has been reported to be as effective as oxybutynin but inducing less dry mouth. Thus, although it is not certain which antimuscarinic drugs have the better efficacy and tolerability, the non-selective antimuscarinic drugs seem to be better than M3-selective antagonists in their clinical efficacies. However, controlled release, or intravesical, intravaginal, or rectal administrations of oxybutynin have been reported to cause fewer side effects. Darifenacin, a new M3 selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To verify which antimuscarinic drugs selective for the muscarinic subtypes have the best efficacy and tolerability, comparative clinical trials between M3 selective antagonists and non-selective compounds, such as olterodine, are required in the future. PMID- 11760778 TI - Potential therapeutic targets for treatment of the overactive bladder. AB - Muscarinic receptor antagonists remain the main therapy for the treatment of the overactive bladder yet severe adverse effects make them unsuitable for a large number of patients. The development of new drugs with novel mechanisms of action for the treatment of this condition is therefore essential. This article considers some of the targets currently under investigation for the development of such compounds. Beta-adrenoceptor agonists and KATP channel openers inhibit detrusor muscle activity and remain targets for drug development. There is also evidence that alpha-adrenoceptor antagonists may be effective in the overactive bladder, but the mechanism involved in this action is unclear. Finally the role of tachykinins in regulating bladder function through both the sensory and the motor innervation make them a potential target for drug development, but as with the the others, a selective action on the bladder must remain the goal of drug development. PMID- 11760779 TI - Tolterodine: an overview. AB - Tolterodine has emerged as a new anticholinergic drug to treat detrusor instability in recent years. This substance and its major metabolite DD01 exhibit a favourable effect-to-side-effect ratio for the bladder. Several clinical studies demonstrated the drug's efficacy in reducing the symptoms of an overactive bladder (urgency, urge incontinence and high micturition frequency) and in increasing functional bladder volume. With a clinical effectiveness comparable to oxybutynin, the side effect-profile measures up favourably to oxybutynin. Consequently, though some limitations need to be addressed, tolterodine can be regarded as the drug of first choice to treat overactive bladders in a variety of patient groups: the young (and otherwise healthy), the elderly, as well as in patients with renal and hepatic insufficiency. A new extended release formula of tolterodine has been launched that may improve patients' compliance. PMID- 11760780 TI - Oxybutynin and the overactive bladder. AB - Oxybutynin is a tertiary amine, which undergoes an extensive first-pass metabolism. It has an active metabolite, N-desethyl oxybutynin, and the effect of oral oxybutynin is to a large extent exerted by this metabolite. Oxybutynin has both an antimuscarinic and a direct muscle relaxant effect, and, in addition, local anesthetic actions. Most probably, oral oxybutynin exerts its effects on the overactive bladder (OAB) by an antimuscarinic action. Several studies have shown that oral oxybutynin is effective in controlling OAB. Admininistred intravesically, it can increase bladder capacity and produce clinical improvement both in patients with hypereflexia and in other types of OAB with few side effects. Adverse effects related to the antimuscarinic activity occur frequently and can necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. A controlled-release preparation has recently been introduced. Oxybutynin has a well-documented efficacy in the treatment of detrusor overactivity, and is a drug of first choice in patients with this disorder. PMID- 11760781 TI - Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). AB - Propiverine hydrochloride (propiverine) is a compound that has neurotropic and musculotropic effects on the urinary bladder smooth muscle. Controlled clinical trials have shown its effectiveness in treating detrusor hyperreflexia and in treating patients with symptoms of an overactive bladder: this is true not only for adults but in children and the elderly as well. European and Japanese studies have also documented that propiverine is well tolerated. It is better tolerated than oxybutynin (particularly in regard to frequency and severity of dryness of the mouth). In several Japanese studies authors demonstrated that propiverine is well tolerated on a long-term basis. Voigt reported an adverse event incidence rate of 13% in a follow-up investigation during 10 years of treatment. A post marketing drug surveillance consisting of 4390 patients provided additional data concerning efficacy and safety of propiverine. It is one of the few drugs recommended for the treatment of detrusor overactivity by the Committee on Pharmacological Treatment during the First International Consultation on Incontinence. PMID- 11760782 TI - Trospium chloride--an effective drug in the treatment of overactive bladder and detrusor hyperreflexia. AB - Trospium chloride (TCL), a quaternary ammonium derivative of nortropanol, has been evaluated in a number of clinical and pharmacological studies. Selected pharmacological and clinical pharmacokinetic data are discussed as providing a basis for a better interpretation and understanding of the clinical trial results. An overview of the results of 20 clinical trials and post-marketing surveillance studies including more than 10000 patients is presented. PMID- 11760783 TI - Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside. AB - Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders. We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis. The results of a larger randomized, double-blind, placebo controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size. Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction. PMID- 11760784 TI - Depression and incontinence. AB - The urologic literature suggests that there is an association between a variety of psychiatric disorders and incontinence. Most notably, depression is found in a significant percentage of patients with urinary incontinence. Depression also occurs in other conditions associated with urinary urge incontinence, such as aging and dementia, and in neurologic disorders such as normal pressure hydrocephalus. Correction of some neurologic disorders eliminates both depression and urge incontinence. Although chronic medical disorders such as urge incontinence may lead to depression, an alternative hypothesis is that these two conditions share a common neurochemical pathogenesis. Lowering monoamines such as serotonin and noradrenaline in the central nervous system (CNS) leads to depression and urinary frequency and a hyperactive bladder in experimental animals. Thus, depression may not only be the result of persistent urinary incontinence, but individuals with altered CNS monoamines could manifest both depression and an overactive bladder. The latter condition may lead to urge incontinence, urinary frequency, urgency, or enuresis. Uncovering further evidence for such a linkage could serve as the basis for the development of genetic markers and novel therapeutic interventions for these two conditions. PMID- 11760785 TI - Quality of life assessment before and after transurethral resection of the prostate in patients with lower urinary tract symptoms. AB - OBJECTIVES: The aim of this study was to determine the effects of surgical treatment of lower urinary tract symptoms (LUTS) in a Malaysian population by evaluating the quality of life before and after treatment. PATIENTS AND METHODS: The study group comprised 111 LUTS patients (age 69.56 +/- 7.94 years, mean +/- SD ) who were assessed 1 week before and at 3, 6 and 12 months after treatment using the health-related quality of life (HRQOL-20) questionnaire, a visual analogue scale (VAS), the present pain intensity (PPI) scale and the international prostate symptom score (I-PSS). RESULTS: Preoperatively the patients suffered more pain, severe prostatic symptoms, impaired disease-specific quality of life and a reduction in health-related quality of life. Postoperatively the patients showed a significant reduction and improvement in pain, prostatic symptoms, and disease-specific and health-related quality of life. CONCLUSIONS: The results showed that the operative procedure significantly improved the overall quality of life of patients with LUTS. PMID- 11760786 TI - Expression, specificity and immunotherapy potential of prostate-associated genes in murine cell lines. AB - The TRAMP-C1 (C1) and TRAMP-C2 (C2) cell lines were derived from a prostate tumor that arose in a mouse from the transgenic adenocarcinoma mouse prostate (TRAMP) model. However, their similarity to primary prostate tumors and therefore their usefulness in immunotherapy studies has not been clearly defined. We showed using RT-PCR that these cell lines exhibited a variety of prostate-specific genes expressed by human prostate tumors that may be used as tumor-associated antigens for immunotherapy. Interestingly, several of these genes are also expressed in cell lines that are not prostatic in origin. The prostate cell lines were also shown to grow in an androgen-independent manner, to be capable of expressing MHC class I and to be susceptible to specific lysis by cytotoxic T lymphocytes. Therefore, these cell lines will provide us with the ability to evaluate immune responses to and tolerance of prostate-specific protein peptides in an animal model. PMID- 11760787 TI - Systemic and cavernosal plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction. AB - The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-l (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated that ET-1 might be involved in the pathophysiology of penile erection. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels recorded in systemic and cavernosal blood taken from healthy males and patients with erectile dysfunction (ED) during different penile conditions (flaccidity, tumescence/rigidity, detumescence). The study groups comprised 33 healthy adult males and 25 patients. The subjects were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET- 1/-2 was determined in plasma aliquots by means of an enzyme-linked immunosorbent assay (ELISA). Mean systemic and cavernosal plasma levels of ET- 1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernosal blood during penile tumescence, rigidity and detumescence. In the patients, mean plasma ET-1/-2 levels during penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernosal blood (flaccidity 0.52 +/- 0.38 fmol/ml vs 0.48 +/- 0.46 fmol/ml, respectively: detumescence 0.53 +/- 0.33 fmol/ml vs 0.27 +/- 0.11 fmol/ ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and those with a psychogenic aetiology of ED. During detumescence, the mean ET-1/-2 level was lower in the cavernosal blood taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-l/-2 in the cavernosal blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seemed to be of no physiological significance, our findings contradict the hypothesis of the ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding the involvement of ET-1 in the pathophysiology of erectile dysfunction. PMID- 11760788 TI - Endocrine response to masturbation-induced orgasm in healthy men following a 3 week sexual abstinence. AB - This current study examined the effect of a 3-week period of sexual abstinence on the neuroendocrine response to masturbation-induced orgasm. Hormonal and cardiovascular parameters were examined in ten healthy adult men during sexual arousal and masturbation-induced orgasm. Blood was drawn continuously and cardiovascular parameters were constantly monitored. This procedure was conducted for each participant twice, both before and after a 3-week period of sexual abstinence. Plasma was subsequently analysed for concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone and testosterone concentrations. Orgasm increased blood pressure, heart rate, plasma catecholamines and prolactin. These effects were observed both before and after sexual abstinence. In contrast, although plasma testosterone was unaltered by orgasm, higher testosterone concentrations were observed following the period of abstinence. These data demonstrate that acute abstinence does not change the neuroendocrine response to orgasm but does produce elevated levels of testosterone in males. PMID- 11760789 TI - The portrait of James Israel by the German impressionist Max Liebermann: a selected pictorial view on the early twentieth century development of surgical urology in Berlin. AB - On the occasion of his retirement from the position as head of the Jewish Hospital in Berlin in 1917, the famous kidney surgeon James Israel (1848-1926) was portrayed by Max Liebermann (1847-1935). At that time both men were leading members of their professions--medicine and fine arts--and represented the Jewish community in Berlin. Private contacts between the surgeon and the artist had been established when Liebermann and his wife needed surgical treatment themselves some years before. Liebermann's later friendship with the surgeon Ferdinand Sauerbruch (1875-1951) culminated in one of the best-known portraits of a member of the medical profession. This biographical article from the history of medicine and fine arts reflecting the relation of these men provides a special view of the development of urological surgery in Berlin at the beginning of the twentieth century. PMID- 11760790 TI - Gadolinium enhancement of cerebrospinal fluid in a patient with renal failure. AB - Gadolinium based MRI contrast agents are considered very safe due to their well known pharmacologic properties and elimination mechanisms. In this paper, we present a unique case in whom transient enhancement of CSF with contrast is seen. Severe renal failure is demonstrated to be responsible for this finding. The diagnostic criteria for everyday clinical setting and possible clinical implications are discussed. PMID- 11760791 TI - Ophthalmic artery calcification in a patient with renal failure. AB - We report calcification in cranial arteries, including the ophthalmic arteries, visible on CT in a patient with diabetes mellitus and renal failure. PMID- 11760792 TI - Long-term clinical outcome of spontaneous carotid cavernous sinus fistulae supplied by dural branches of the internal carotid artery. AB - We report the long-term clinical outcome of spontaneous carotid cavernous sinus fistulae (CCF) originally supplied by branches arising from the internal carotid artery (Barrow's type B), or type-D lesion that became type B after particulate embolization. A total of 55 patients was included in this study. Their angiography revealed that cortical drainage was absent, and that the arteries supplying the fistulae originated in the dural branches of the internal carotid artery. Thirty-two patients had type-D lesions, which became type-B lesions after obliteration of the external carotid supply by endovascular treatment. The other 23 patients had type-B lesions documented by angiography, and had no embolization. The follow-up period ranged from 8 to 144.5 months. Clinical cure was achieved in 39 patients (70.9%), improvement in eight patients (14.5%), the lesion remained stable in four patients (7.3%), and was aggravated in four patients (7.3%). The number of drainage veins is the only radiographic factor that could predict the outcome. Those patients with single draining veins had a better chance of complete remission. The outcome between the group with original type D lesions after embolization and the group with original type B revealed no statistically significant difference. The time-course to complete cure was significantly shorter in the group with embolization of the external carotid supply. In the four patients whose symptoms were aggravated, embolization was performed, and the result was excellent. The clinical outcome of type-B CCF, or type D converted to type B, is good. Previous external carotid artery embolization can significantly shorten the time to complete cure. Aggressive treatment should be reserved for those who have aggravated symptoms. PMID- 11760793 TI - Thyroglossal duct calcifications. PMID- 11760794 TI - Diffusion-weighted imaging in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. AB - The purpose of our study was to determine the usefulness of echo-planar diffusion weighted imaging (EPDI) in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. Eighteen patients ranging in age from 3 weeks to 12 years were evaluated for evidence of ischemic/infarction changes on conventional MR and EPDI. Included in the study group were five patients with sickle cell disease, four with congenital heart disease, four with hypotensive episodes with various etiologies, three with sepsis, and two with encephalitis or meningitis. Patients were examined 2 h to 6 days after the initial insult, with follow-up studies in four patients at 1 to 62 days after the initial examination. After conventional MR imaging (T1, FSE T2, and FLAIR), diffusion-weighted MR imaging was performed using high-speed, single-shot EP techniques with TR 6000, TE 144, matrix 96 x 128, FOV 23.3 x 31 and five b values of 0, 160, 360, 640, and 1,000 s/mm2. EPDI demonstrated abnormally increased signal in watershed ischemic/infarction zones in all initial cases. Apparent diffusion coefficients (ADC) were obtained in 59 lesions. When compared with radiographically normal (on EPDI) contralateral brain parenchyma, 45 demonstrated a relatively decreased ADC, while eight had normal ( +/- 10%) and six had increased ADC. In four cases, signal abnormalities on EPDI were not seen or exceeded that seen with conventional MR imaging. In the remaining cases, signal abnormalities were obvious on EPDI and more subtle on conventional MR imaging. Follow-up studies demonstrated resolution of abnormal EPDI signal with persistent abnormalities on conventional imaging in some cases, while others revealed an increase in size or number of EPDI signal abnormalities, suggesting ongoing acute ischemic/infarctive changes. EPDI is a rapid, sensitive technique for detecting watershed ischemic/infarction changes in pediatric patients with hypoperfusion episodes, at times before such changes are apparent on conventional MR images and/or are clinically apparent. PMID- 11760795 TI - Diffusion-weighted imaging and fluid attenuated inversion recovery imaging in the evaluation of primitive neuroectodermal tumors. AB - The aim of our study was to determine whether fluid-attenuated inversion recovery (FLAIR) imaging and diffusion-weighted imaging (DWI) would be helpful in characterizing primitive neuroectodermal tumors (PNET) from other pediatric brain tumors. We expected that the compact cellular nature and the relatively small extracellular space of this tumor would affect the signal intensity on both pulse sequences relative to the more sparsely cellular glial tumors that have larger extracellular spaces. Eighteen pediatric patients with PNET were examined on a 1.5 T MRI with routine imaging plus FLAIR and compared with 28 patients with nonPNET. DWI was also performed in 7 PNET and 18 non-PNET. Seventyeight percent of PNET were isointense to gray matter on FLAIR while 82% of non-PNET were hyperintense and only one was isointense (3%). Diffusion was abnormally restricted in all 7 PNET examined (100%) but was restricted in non-PNET in only 1 out of 18 (6%) patients who had DWI. The differences in the histologic architecture between PNET and non-PNET are reflected in both FLAIR imaging and in DWI. PMID- 11760796 TI - Posterior fossa and arterial abnormalities in patients with facial capillary haemangioma: presumed incomplete phenotypic expression of PHACES syndrome. AB - We report on the neuroradiological studies performed on three infants with capillary haemangioma (CH) of the head and neck with associated posterior fossa and arterial abnormalities. Posterior fossa malformations were represented by cerebellar hemispheric and vermian hypoplasia and cerebellar cortical dysgenesis, whereas arterial anomalies included bilateral agenesis, kinking, and looping of the internal carotid arteries. One patient had marked exophthalmos due to intraorbital CH. We suggest that these patients had an incomplete phenotypic expression of PHACES syndrome, a vascular phakomatosis characterised by the variable association of posterior fossa malformations, CH, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal and medioventral defects. Evidence suggests that PHACES syndrome is not a random association but a true phakomatosis; further studies are awaited to shed light on a possible genetic background. The phenotypic spectrum is broad and still largely unexplored, and precise diagnostic criteria have not yet been identified. A causal teratogenic influence, possibly related to anomalous expression of vascular growth factors and their modulators, is suggested to occur between gestational weeks 3 and 5.5 PMID- 11760797 TI - MRI of mannosidosis. AB - MR findings in three patients with mannosidosis are reported. They all had diploic space widening with underdevelopment of the sinuses, prominent periventricular Virchow-Robin spaces and perioptic CSF spaces. Two had tight foramen magnum, one of which was associated with a cervical syrinx and markedly widened perioptic CSF spaces with papilledema. PMID- 11760798 TI - Melanotic neuroectodermal tumour of the pineal region. AB - We describe CT and MR findings in a 23-month-old infant with a melanotic neuroectodermal tumour of the pineal gland. The tumour has been stereotactically biopsied and surgically resected. The pathological diagnosis was made on the resected piece. Embryology of the pineal gland and the histology of melanotic neuroectodermal tumour of infancy are discussed. PMID- 11760799 TI - Menkes' disease with a Dandy-Walker variant: case report. AB - We report a boy with Menkes' disease in whom MRI revealed delayed myelination of the white matter, brain atrophy and tortuosity of the intracranial vessels. The characteristic MRI features of Menkes' disease were accompanied by a Dandy-Walker variant. PMID- 11760800 TI - MRI findings in an asymptomatic boy with X-linked adrenoleukodystrophy and his symptomatic mother. AB - We report an asymptomatic 15-year-old boy with X-linked adrenoleukodystrophy and his symptomatic 38-year-old mother. MRI revealed similar, subtle high-signal lesions in the periventricular white matter of the parieto-occipital regions, without involvement of the corpus callosum, more pronounced in the mother. PMID- 11760801 TI - Anatomy of brain-stem white-matter tracts shown by diffusion-weighted imaging. AB - We acquired high-resolution MRI and anisotropically diffusion-weighted images (DWI) with direction-selective gradients of the brain stem in 20 healthy volunteers, to identify brain-stem structures such as white-matter tracts and nuclei which show diffusion anisotropy. After averaging and superposition of individual cuts, the images were projected onto appropriate plates of the Schaltenbrand and Wahren anatomical atlas. We identified 20 structures--white matter tracts and some nuclei--with high contrast. The direction of fibres could be determined as areas of increased (parallel to) or decreased diffusion (perpendicular to the gradient). This study may contribute to understanding of the functional anatomy of the brain stem. PMID- 11760802 TI - MR imaging in intramedullary cysticercosis. AB - Although intramedullary spinal cord cysticercosis (IMC) is uncommon, its presence is being increasingly recognised by magnetic resonance imaging. We studied six patients from an endemic region and present the MRI features and clinical correlation of IMC. Six patients who presented with para- or quadriplegia were studied by contrast enhanced spinal MRI. Prompted by the spinal lesions, all patients underwent brain MRI. Clinical data and laboratory studies were reviewed in all patients. Definite diagnosis was established in the form of response to drug therapy (n = 4) and histopathology (n = 2). Follow-up MRI studies of spine and brain were obtained in four patients 2 months after they started medical treatment, regardless of surgery. Five patients showed fusiform and focal enlargement of the spinal cord (cervical 2, thoracic 3). Well-defined cysts with a slightly hyperintense mural nodule were identified in five patients in Ti weighted images (T1WI). All cysts were hyperintense on T2WI and merged with the surrounding oedema. Oedema extended one to three vertebral levels above or below the cyst. Post-contrast T1WI showed well-defined, ring enhancing lesions with smooth walls in all patients. Symptoms in all patients correlated with the level of the lesions. Brain studies demonstrated lesions in just two patients. Histopathological confirmation was obtained in two patients. Follow-up spinal MRI was normal in two patients, following 2 months of treatment while residual and smaller lesions were seen in two patients. Two patients were asymptomatic and denied follow-up MRI. MRI of spinal cysticercosis were typical of and similar to those seen in cerebral lesions in our patients and corresponded to the level of symptoms. All cysts were surrounded by oedema. Two of four patients showed residual lesions after 2 months of therapy and 33 % of patients showed concomitant intracranial lesions. PMID- 11760803 TI - Diffusion-weighted MR in reversible wernicke encephalopathy. AB - Diffusion-weighted images (DWI) of a patient with Wernicke encephalopathy were obtained during routine MR examination. Mammillary bodies were hyperintense on T2 weighted and enhanced on T1-weighted images; on DWI, a mild hyperintensity was noticed. Calculation of the apparent diffusion coefficient (ADC) demonstrated an increased diffusion on the affected regions; the hyperintensity on DWI was probably due to a "T2-shine-through" effect. These findings are consistent with the presence of extracellular oedema, without significant neuronal damage. The patient recovered promptly after thiamine administration, and MR alterations disappeared. The favourable evolution indicates that no relevant neuronal death occurred. This is consistent with DWI findings. DWI are more sensitive than ordinary T1- and T2-weighted images to neuronal irreversible damage, and may differentiate between neuronal necrosis and extracellular oedema in various brain pathologies. The demonstration of a limited neuronal damage may represent a favourable prognostic factor in patients with WE. PMID- 11760804 TI - Familial form of cerebral cavernous malformations: evaluation of gradient-spin echo (GRASE) imaging in lesion detection and characterization at 1.5 T. AB - The purpose of this study was to evaluate the turbo gradient-spin-echo sequence (GRASE) in the MR assessment of the familial form of cerebral cavernous malformations (CCM). Twenty-one patients (15 male, six female) aged from 21 to 68 years (mean = 42.2 years) were prospectively examined with cerebral MR imaging, including T2-weighted turbo gradient-spin-echo (TGSE), turbo spin-echo (TSE) and gradient-echo (GRE) sequences. All sequences were performed in the same plane, the same matrix and the same field of view and were analyzed for signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), susceptibility effects, number of CCM, size of CCM and signal of CCM. It was found that SNR and CNR in the TGSE sequence were significantly inferior to those in both TSE and GRE sequences. TGSE and TSE sequences were significantly less prone to susceptibility effects than the GRE sequence. The sensitivity of TGSE and TSE sequences in detecting CCM was significantly lower than that of the GRE sequence. TGSE and TSE sequences provided comparable information about CCM size and signal. It was concluded that GRASE imaging was less sensitive than the GRE sequence in the detection of CCM and provided information similar to that yielded by the TSE sequence in the characterization of lesions, but with a higher number of artifacts. GRASE imaging cannot therefore replace TSE or GRE sequences in the MR evaluation of the familial form of CCM. PMID- 11760805 TI - The importance of venous hypertension in the formation of dural arteriovenous fistulas: a case report of multiple fistulas remote from sinus thrombosis. AB - Various hypotheses have been reported concerning the pathogenesis of dural arteriovenous fistulas (DAVFs). However, it is still controversial whether sinus thrombosis or venous hypertension has a greater influence on the formation of DAVFs. We present a rare case of multiple DAVFs that developed after sinus thrombosis. Chronic venous hypertension secondary to sinus thrombosis in the left transverse-sigmoid sinus induced the multiple DAVFs, including one in the right cavernous sinus, which was remote from the occluded sinus. This case indicates the importance of venous hypertension in the formation of DAVFs. PMID- 11760806 TI - Bleeding from a cavernous angioma mimicking rupture of a middle cerebral artery aneurysm. AB - Cavernous angiomas and aneurysms may both present with acute cerebral haemorrhage. We present a case in which the coexistence of an unruptured aneurysm obscured the diagnosis of cerebral haemorrhage from a cavernous angioma. Although this association was presumably coincidental, this case demonstrates that obvious pathology (an angiographically proven aneurysm at the site of haemorrhage) may reduce awareness of other, possibly more common, causes of cerebral haemorrhage. PMID- 11760807 TI - Fusiform aneurysms detected 5 years after removal of an atrial myxoma. AB - Neurological signs frequently accompany atrial myxomas. Association of multiple cerebral aneurysms in patients with atrial myxomas are less common than embolic infarctions. The development of aneurysms years after the cardiac tumor removal is rare, and few MR images have been reported to date. A case of multiple peripheral fusiform aneurysms detected 5 years after tumor resection is presented in this report, together with MR images and CT and angiographic images. PMID- 11760808 TI - Brain PET and technetium-99m-ECD SPECT imaging in Lhermitte-Duclos disease. AB - Two patients with Lhermitte-Duclos disease were evaluated by brain positron emission tomography (PET) and technetium-99m-ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT). In the lesions in both patients, hyperperfusion was detected on cerebral blood flow images obtained by PET, and hyperactivity by standard 99mTc-ECD SPECT. Dynamic 99mTc-ECD SPECT images demonstrated a plateau of activity in each lesion. These findings suggest that lesions in Lhermitte-Duclos disease have a retention mechanism for 99mTc-ECD equivalent to that of normal neural tissue. PMID- 11760809 TI - Parkinson's disease associated with impaired oxidative phosphorylation. AB - Parkinson's disease may be due to primary or secondary oxidative phosphorylation (OXPHOS) defects. In a 76-year-old man with Parkinson's disease since 1992, slightly but recurrently elevated creatine phosphokinase, recurrently elevated blood glucose, thickening of the left ventricular myocardium, bifascicular block and hypacusis were found. Cerebral MRI showed atrophy, periventricular demyelination, multiple, disseminated, supra- and infratentorial lacunas, and haemosiderin deposits in both posterior horns. Muscle biopsy showed typical features of an OXPHOS defect. Whether the association of Parkinson's disease and impaired OXPHOS was causative or coincidental remains unknown. Possibly, the mitochondrial defect acted as an additional risk factor for Parkinson's disease or the OXPHOS defect worsened the preexisting neurological impairments by a cumulative or synergistic mechanism. In conclusion, this case shows that Parkinson's disease may be associated with a mitochondrially or nuclearly encoded OXPHOS defect, manifesting as hypacusis, myopathy, axonal polyneuropathy, cardiomyopathy and recurrent subclinical ischaemic strokes and haemorrhages. PMID- 11760810 TI - Scientific analysis of the proposed uses of the T25 dose descriptor in chemical carcinogen regulation. AB - The uncertainties that surround the methods used for risk assessment of exposure to carcinogens have been highlighted by a recent document advocating an approach based on the T25 dose (the dose giving a 25% incidence of cancer in an appropriately designed animal experiment). This method relies on derivation of the T25 dose then assesses risk at the exposure dose using proportionality provided by a linear extrapolation (T25/linear). To promote discussion of the scientific issues underlying methods for the risk assessment of chemical carcinogens, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) hosted a one-day workshop in Brussels on 10 November 2000. Several invited presentations were made to participants, including scientists from regulatory authorities, industry and academia. In general, it was felt that there was sufficient basis for using the T25 dose as an index of carcinogenic potency and hence as part of the hazard assessment process. However, the use of the T25 in risk assessment has not been validated. The T25/linear and other extrapolation methods based on metrics such as LED 10 assume linearity which may be invalid. Any risk calculated using the T25/linear method would provide a precise risk figure similar to the output obtained from the Linearised Multistage (LMS) method formerly used by the Environmental Protection Agency (EPA) in the United States of America. Similarity of output does not provide validation but rather reflects their reliance on similar mathematical approaches. In addition to the T25 issue, evidence was provided that using two separate methods (linearised non-threshold model for genotoxic carcinogens; no-observable-effect level with a safety factor (NOEL/SF) method for all other toxicity including non-genotoxic carcinogens) is not justified. Since the ultimate purpose of risk assessment is to provide reliable information to risk managers and the public, there was strong support at the workshop for harmonisation of approaches to risk assessment for all genotoxic and nongenotoxic carcinogens. In summary, the T25 method has utility for ranking potency to focus efforts in risk reduction. However, uncertainties such as the false assumption of precision and non-linearity in the dose-response curve for tumour induction raise serious concerns that caution against the use of T25/linear method for predicting human cancer risk. PMID- 11760812 TI - Bioavailability of cadmium from infant diets in newborn rats. AB - Infants are exposed to higher levels of cadmium (Cd) from infant and follow-on formulas than from breast milk. We studied the bioavailability of 109CdCl2 from cows' milk formula, soy formula, wheat/oat/milk formula, wholemeal/milk formula and water in 11-day-old rat pups. The pups received a single oral dose of one diet labelled with 109Cd, 0.1 or 0.3 mg Cd/kg body weight. After 2 or 24 h or 4, 9 or 12 days the fractional retention of 109Cd in the whole body, in segments of rinsed small intestine and in tissue was measured in a gamma counter. Pups receiving 109Cd in water or cows' milk formula had the highest mean whole-body retention. It ranged from 67% of the dose in the water group to 52% in the wholemeal/milk formula group 4 days after dosing. The retention of 109Cd in the rinsed small intestine was significantly higher in the water group and the cows' milk formula group than in the cereal-based formula groups at 24 h and 4 days after dosing. It was still high in all groups on day 9, ranging from 26 to 11%. Initially most of the 109Cd was retained in the duodenum but by day 4 it had moved further down into the jejunum. In the liver, the highest and lowest retention on day 4 was 16%, and 3 per thousand of the dose in the water group and wholemeal/milk formula group, respectively. In the kidney, 109Cd was still increasing 12 days after exposure in all groups. Whole-body retention and tissue levels were higher than previously reported in adult animals. The lower bioavailability of 109Cd from the cereal-based formulas compared to water and cows milk formula on the longer survival times is most likely explained by Cd binding to dietary fibre and phytic acid in the cereal-based formulas reducing the intestinal binding and decreasing the bioavailability of Cd. The high retention of 109Cd in the small intestine, leading to a prolonged absorption period, emphasizes the importance of extending studies on neonatal Cd absorption over a long time period in order to detect for example, endpoints, accumulation of Cd in the kidney. PMID- 11760811 TI - A repeated 28-day oral dose toxicity study of methoxychlor in rats, based on the 'enhanced OECD test guideline 407' for screening endocrine-disrupting chemicals. AB - In association with the international validation project to establish an OECD Enhanced Test Guideline 407, we performed a 28-day repeated-dose toxicity study of methoxychlor, a chlorinated hydrocarbon pesticide with pro-estrogenic and anti androgenic activities. Attention was paid to the sensitivity of certain additional parameters for detecting endocrine related effects of endocrine disrupting chemicals based on the existing TG 407. Seven-week-old Crj:CD(SD)IGS rats were allocated to one of four groups, each consisting often males and ten females, and methoxychlor was administered once daily by gavage at doses of 0 (control), 20, 100 or 500 mg/kg body weight per day. Male rats were killed on the day after the 28th administration. Female rats were killed on the day of the diestrus stage during 4 days after the 28th administration. Male rats receiving methoxychlor showed mainly atrophy of mammary acinus in the 20 mg/ kg and higher groups, together with decreases in prostate and seminal vesicle weights, and atrophy of epididymis, prostate, seminal vesicle and coagulating gland in the 100 and 500 mg/kg groups. In addition, decrease in serum testosterone level, increase in follicle-stimulating hormone level, decrease in testis and epididymis weights, atrophy of semiferous tubules and Leydig cells, decrease in the number of sperm in the caudal epididymis and their motility were observed in the 500 mg/kg group. Female rats receiving methoxychlor showed mainly abnormal estrous cycles, decrease in serum luteinizing hormone level, decrease in ovary weight, proliferation of mammary acinus, atrophy of ovary due to decrease in follicles and corpus luteum in histopathology, hypertrophy of endometrial epithelium of uterus and vagina epithelium in the 100 and 500 mg/kg groups. Among the parameters tested in the present experimental system, effects of methoxychlor on endocrine-related organs were detected with regard to serum hormone, organ weights, histopathological examination in both sexes, estrus cycle in females and sperm examination in males. Based on these results, a no-observed-adverse-effect level (NOAEL) in the present study was estimated to be below 20 mg/kg per day. In particular, the adverse effects were effectively detected in organ weights of accessory sex organs and histopathological examination. PMID- 11760813 TI - Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. AB - Arsenic is a potent toxin, carcinogen and modulator of antioxidant defense system. In this study, male rats of Wistar strain, maintained on either 18% or 6% protein (casein) diet, received an acute i.p. exposure to sodium arsenite (As3+) at its LD50 dose (15.86 mg/kg body weight). One hour after the arsenic exposure, glutathione (GSH) concentration was significantly depleted and lipid peroxidation was increased. A relationship between any two of tissue arsenic concentrations, GSH levels and lipid peroxidation values was observed only for liver when the proportional changes of respective parameters in either of the dietary groups of animals were compared. This suggests that, in liver, arsenic metabolism appears dependant upon the GSH concentration. Acute arsenic exposure significantly increased the glutathione peroxidase (GPx) activity in liver of both dietary groups and in kidney of only the 18% protein-fed group of animals. The glutathione-S-transferase (GST) activity significantly decreased in liver of the 18% protein-fed animals while GST increased in kidney of both the 18% and the 6% protein-fed groups. No significant change in glutathione reductase (GR) or glucose-6-phosphate dehydrogenase (G6PDH) activity was observed. In the present investigation, liver as a whole seems to be more affected in terms of GSH level and GST activity. The mode of responses of GPx and GR activities as well as the unaltered G6PDH activity might result in arsenic-induced GSH depletion and increase in lipid peroxidation. The animals of the 6% protein-fed group, appeared to be affected less in terms of tissue arsenic concentration, GSH level and GST activity. lipid peroxidation, PMID- 11760814 TI - Differential selectivity in carbamazepine-induced inactivation of cytochrome P450 enzymes in rat and human liver. AB - Oxidative metabolism of carbamazepine results in covalent binding of its reactive metabolite to liver microsomal proteins, which has been proposed as an important event in pathogenesis of the hypersensitivity reactions to this drug. Although the proposed reactive metabolites are produced by cytochrome P450 enzymes (P450 or CYP), the impact of the formation of unstable metabolites on the enzyme itself has not been elucidated. The present study examines the alteration of P450 enzyme activities during the metabolism of carbamazepine. Liver microsomes from rats and humans were preincubated with carbamazepine in the presence of NADPH, and subsequently assayed for monooxygenase activities representing several P450s. No evidence was obtained for inactivation of CYP2C11, CYP3A, CYP1A1/2 or CYP2B1/2 in rat liver microsomes during the carbamazepine metabolism, whereas the CYP2D enzyme was inactivated in a manner related to the preincubation time. Interestingly, under the same protocol human liver microsomes did not exhibit inactivation of CYP2D6, as well as there being no CYP2C8, CYP2C9 or CYP3A4 inactivation, whereas CYP1A2 was inactivated. Reduced glutathione could not protect against the observed inactivation of the P450s. These results suggest that CYP2D enzyme(s) in rats and CYP1A2 in humans biotransform carbamazepine into reactive metabolites, resulting in inactivation of the enzyme themselves, and raise the possibility that the P450 isoforms participate in toxicity induced by the drug in both animal species. PMID- 11760815 TI - Dependence of papanicolaou gradings of exfoliated urothelial cells upon GSTM1 and GSTT1 polymorphism in benzidine-exposed workers of the Shanghai dye industry. AB - The distribution of the polymorphic alleles of the genes coding for glutathione S transferases (GSTs) M1 and T1 was compared with the results of cytological grading of exfoliated urothelial cells (Pap test) in a non-diseased high-risk group of workers formerly exposed to benzidine in the Shanghai dyestuff industry (n = 317). All subjects were genotyped for GSTT1 and M1 gene polymorphism by allele-specific PCR. Individuals were stratified according to their job and duration of exposure. A subgroup of 78 individuals with cytological gradings of grade III or higher in the Pap test showed a significant under-representation of the combination of GSTT1 0/0 and M1 0/0 genotypes compared with 238 subjects with a cytological classification lower than grade III (OR 0.55, 95% CI 0.31-0.98. P=0.04). These results suggest that neither the GSTM1 0/0 or GSTT1 0/ 0 genotype alone nor their combination had a clear association with cytopathological changes in exfoliated urothelial cells from individuals previously exposed to benzidine in Shanghai. This contradicts the results of studies indicating that the GSTM1 0/0 genotype is associated with an increased risk for bladder cancer in the general population, mostly outside China. PMID- 11760816 TI - Effect of tributyltin on the N-methyl-D-aspartate (NMDA) receptors in the mouse brain. AB - The purpose of this study was to determine the effect of tributyltin chloride (TBTCI) on the NMDA receptor by in vitro and in vivo experiments. In the first in vitro experiment, the binding of [3H]MK-801 and of [3H]-CGP39653 were studied in membrane preparations from the cerebral cortex of intact mice to obtain control values. Saturation experiments for [3H]MK-801 and [3H]CGP39653 revealed single binding sites with Kd values of 10.27 and 37.8 nM, and receptor densities of 1.75 and 2.20 pmol/mg of protein, respectively. In the second in vitro experiment, displacement studies were carried out with TBTCI over a concentration range of 0.1 microM to 2 mM. TBTCI inhibited [3H]MK-801 binding but did not affect [3H]CGP39653 binding. In the in vivo experiments, the mice received 1-125 ppm TBTCI in the diet ad libitum for 30 days. Ligand binding to cortical membrane preparations from each mouse was measured by a one-concentration point (2 nM) binding assay. [3H]MK-801 binding was significantly lowered (P < 0.05) in the 5 and 125 ppm TBTCl-exposed animals compared with the controls. [3H]CGP39653 binding was also significantly lowered (P<0.05) in the 1 and 125 ppm TBTCI exposed animals compared with the controls. These results suggest that the NMDA receptors in the mouse brain are sensitive to relatively low level exposure to TBTCl. PMID- 11760817 TI - Toxicity and effects of 2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate (terbutol) on hepatic cytochrome P450 in F344 rats. AB - The subacute toxicity and effects of 2,6-di-tert-butyl-4-methylphenyl N methylcarbamate (terbutol) on hepatic microsomal cytochrome P450 (P450) were investigated in male and female F344 rats. Rats were given 0.25, 0.5, and 1.0% terbutol for 28 days. Liver weights of male and female rats increased at all dose levels. The compound did not affect activity or amount of serum biochemical markers related to hepatic damage. The concentrations of terbutol in rat serum were less than 0.1 microM, and its major metabolites in serum were 2,6-di-tert butyl-4-carboxyphenyl N-methyl-carbamate and 2,6-di-tert-butyl-4-carboxyphenol. In male rats, P450 and cytochrome b5 (b5) contents, and NADPH cytochrome c reductase (fp2) activity in liver microsomes were increased about 2-fold by 1% terbutol administration for 7 to 28 days. Among the P450-dependent monooxygenase activities in liver microsomes, 7-benzyloxyresorufin-O-debenzylase (BROD) activity was greatly increased by 100-fold, and 7-ethoxyresorufin-O-deethylase (EROD), 7-ethoxycoumarin-O-deethylase (ECOD), and aminopyrine-N-demethylase (APND) activities were elevated 2- to 3-fold. 7-Methoxyresorufin-O-deethylase (MROD), erythromycin-N-demethylase (EMND), estradiol 2-hydroxylase (ED2H), chlorzoxazone 6-hydroxylase (CZ6H), and lauric acid omega-hydroxylase (LAOH) activities were unchanged. For the activities of testosterone hydroxylation, testosterone 16beta-hydroxylase (T16BH) activity was markedly increased by 30 fold, and testosterone 6beta-hydroxylase (T6BH) and testosterone 7alpha hydroxylase (T7AH) activities were slightly elevated. Testosterone 2alpha hydroxylase (T2AH) activity was not affected. Terbutol 4-methylhydroxylase (T4MH) activity was increased 9-fold by 1% terbutol. In an immunoinhibition study, T4MH activity in liver microsomes from 1% terbutol-treated rats was decreased about 50% by polyclonal anti-rat CYP2B1, whereas polyclonal anti-rat CYP2A1 and CYP2C11 did not affected the activity. These results indicate that terbutol increased CYP2B subfamily in rat liver microsomes, and that the compound did not cause serious hepatic damage. PMID- 11760819 TI - Eight years of unexplained headaches (why did the diagnosis take so long?). AB - The patient had chronic incapacitating headaches for a period of eight years. Neurologic tests ruling out organic causes such as tumors and analysis of diet, allergies, stress levels, and chronic infections left the patient and physicians without an explanation. The headaches did not fit the patterns of common or classic migraines. The patient's energy level had significantly decreased during this same time period, and she had frequently become short of breath. Diagnosis of underlying pathology occurred when efforts were focused on explaining respiratory conditions. The patient had an oxygen saturation of 77% and a pulse of 98, following a brief walk around the building. Further testing by a pulmonary specialist confirmed diagnosis of emphysema secondary to a deficiency of Alpha-1 Antitrypsin (AAT). Background materials supporting this case history include: a model for AAT function, genetics of AAT deficiency, pathophysiology of both liver and pulmonary diseases, and a summary of treatment options and prognosis for AAT deficient patients. PMID- 11760818 TI - The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human relevant doses. AB - 7-Acetyl-1,1,3,4,4,6-hexamethyl- 1,2,3,4-tetra-hydronaphthaline (AHTN) is one of the two most widely used fragrances of a group of substances known collectively as the polycyclic musks. In the last few years evidence has been accumulating that AHTN is hepatotoxic when administered at high doses. In the present study the subchronic hepatotoxicity of AHTN administered to rats at doses within the human exposure range was evaluated. For this purpose female and male juvenile Wistar rats were exposed to AHTN (300 microg/kg body weight per day, i.p.) alone or to a single dose of diethylnitrosamine (DEN) (100 mg/kg body weight, i.p.) followed by AHTN (1, 10, 100 or 300 microg/kg body weight per day, i.p.) for 90 days. Thereafter the liver architecture as well as the presence of placental glutathione S-transferase (GST-P)-positive hepatic lesions was assessed. In male animals receiving AHTN alone or in combination with DEN the number of GST-P positive single hepatocytes was similar to that in untreated rats, while GST-P positive mini-foci and foci were not observed. In the case of female rats the number of GST-P-positive single hepatocytes and mini-foci in AHTN-treated rats was similar to that in untreated animals, whereas in those animals receiving AHTN either alone or in combination with DEN, GST-P-positive foci could not be detected or were present in a number as similar to that in untreated rats. In conclusion, in the present study it has been shown that AHTN administered over a 90-day period in concentrations similar to those taken up daily by humans does not lead to hepatotoxicity. PMID- 11760820 TI - B-Prolymphocytic leukemia: a case study. AB - The case study reported is of a patient initially misdiagnosed as chronic lymphocytic leukemia. Immunophenotyping studies ultimately identified the nature of the disease as B-cell prolymphocytic leukemia with concomitant warm autoimmune hemolytic anemia. The leukemia and hemolytic anemia were refractory to all conventional treatments administered. The patient survived a significantly shorter period of time than the median time of three years reported in the literature. The patient expired from complications resulting from B-cell PLL, warm autoimmune hemolytic anemia, and combination chemotherapy. PMID- 11760821 TI - Comparison of four automated hematology analyzers. AB - OBJECTIVE: To compare four automated hematology analyzers for efficiency and sensitivity. DESIGN: Four automated hematology analyzers were compared in a side by side study: Bayer ADVIA 120 (Bayer Diagnostic Division, Tarrytown, NY), Beckman Coulter GEN S (Beckman Coulter, Brea, CA), Abbott CELL DYN 3500 and CELL DYN 4000 (Abbott Diagnostics, Santa Clara, CA). 164 specimens were analyzed for cell counts, indices, and the automated WBC differential (DLC). Tallies were kept of all interventions, defined as any parameter necessitating examination of a stained blood smear by a clinical laboratory scientist. A 400-cell manual differential was performed on each specimen and used as the reference to prepare truth tables for each type of WBC. PATIENTS: Specimens comprised regular runs from this tertiary care teaching hospital. These included inpatients, outpatients, and oncology patients, including bone marrow transplant patients. MAIN OUTCOME MEASURES: Results from the truth tables were used for calculating sensitivity and efficiency for each analyzer. Each DLC parameter was analyzed for variance using the one-way ANOVA test. RESULTS: No intervention was required for 103 of 164 specimens for the CELL DYN 3500; the ADVIA gave 70 reportable DLCs without intervention, the GEN S provided 91 and the CELL DYN 4000 resulted in 117 of 164 DLCs without intervention. Agreement or efficiency was 65% for the CELL DYN 3500, 41% for the ADVLA, 58% for the GEN S, and 79% for the CELL DYN 4000. Sensitivity was 67% for the CELL DYN 3500, 86% for the ADVIA, 76% for the GEN S, and 71% for the CELL DYN 4000. Probability of significant variation was as follows for each parameter: % neutrophil 0.8747, % lymphocyte 0.8830, % monocyte 0.0296, % eosinophil 0.7903, and % basophil <.0001. CONCLUSION: The analyzers tested were acceptable for routine laboratory work. Selection would depend on individual need with respect to sensitivity and efficiency. The clinical significance of disagreement between the DLC and the manual differential remains to be determined. PMID- 11760822 TI - The use of high sensitivity C-reactive protein in assessing the risk for coronary heart disease. PMID- 11760823 TI - Health services implications of DNA testing. AB - This review article summarizes the state of the art in genetic testing and discusses the many issues that new technologies have raised. A health services perspective is offered to aid in providing laboratorians with an understanding of the dilemma that society faces with the exponential advances in knowledge. Unmistakably, these new technologies are a mixed blessing: on the one hand, diagnoses can be made with greater accuracy and preventive measures implemented more fruitfully and individuals may be more conclusively identified and/or exonerated for forensic purposes. On the other hand, however, are the very real concerns that discrimination under a medical guise will be encouraged and that privacy rights may be compromised. Another important issue is how the laboratory profession will serve in moving these new technologies from research to practice. We examine the role of the CLS in moving forward to a role of patient counselor and advocate in the emerging complex world of DNA-related biotechnology. PMID- 11760824 TI - The new millennium laboratory: molecular diagnostics goes clinical. AB - Applications of nucleic acid testing in most areas of the clinical laboratory have increased rapidly. The advantages of nucleic acid testing include enhanced specificity and sensitivity, ease of sample procurement, and more rapid turnaround time compared to conventional laboratory testing methods. However, the cost of testing is usually higher due to the need for additional laboratory space, specialized equipment, safety apparel, and the need for highly trained personnel. Most nucleic acid techniques currently used in a clinical setting can be categorized as either hybridization or amplification assays. Hybridization assays, including blotting techniques and microarrays, involve the complementary binding of an oligonucleotide probe of known DNA sequence with nucleic acid derived from the patient sample. To amplify small amounts of nucleic acid, assays such as the polymerase chain reaction and branched chain DNA employ either signal amplification or exponential amplification of target nucleic acid. Clinical applications of nucleic acid testing involve the detection of genetic diseases, e.g., sickle cell anemia and Huntington disease; and identification of infectious agents, e.g., HCV and HIV; or malignancies, e.g., chronic myelogenous leukemia and Burkitt lymphoma. Quantitative molecular assays also play important roles in predicting prognosis and monitoring responsiveness to therapy. PMID- 11760825 TI - Laboratory results that predict arterial thrombosis. AB - This focus section reviews the laboratory markets now available for predicting the risk of cardiovascular disease. The three most often ordered are: fibrinogen, described by David Golec of Esoterix Coagulation; homocysteine, reviewed by Paige Macy of Esoterix Coagulation; and high-sensitivity C-reactive protein, reviewed by George Fritsma of the University of Alabama at Birmingham coagulation service. Following is a brief review of cardiovascular disease. PMID- 11760826 TI - Fibrinogen and thrombophilia. AB - The objective of this article is to illustrate the significant relationship between fibrinogen and thrombophilia, the tendency toward clot formation. This deserves attention because thrombus formation leads to disease states such as pulmonary embolism, peripheral vascular disease, and cardiovascular disease (CVD). The latter holds the distinction of being the leading cause of mortality among the U.S. population. Elevated levels of plasma fibrinogen have been correlated with increased risk of ischemic events. Its relationship is even stronger than that of increased total cholesterol. Many studies have demonstrated that fibrinogen is a potent predictor of coronary artery disease, and it is also positively associated with stroke. For all of its predictive power, fibrinogen's use as a yardstick for cardiovascular risk has not gained widespread acceptance. The problem with fibrinogen as a clinical tool for predicting coronary events is that laboratory measurement is not standardized, and specific clinical interventions to lower fibrinogen levels are not available. Fibrinogen is also an acute phase reactant. It fluctuates with the onset of inflammatory stares. When there is a change in the structure of the fibrinogen molecule, either by hereditary or acquired conditions, there can be dramatic effects, or none at all. Since fibrinogen plays several roles in maintaining hemostatic balance, abnormalities in molecular composition can be reflected in various ways, including thrombus formation. PMID- 11760827 TI - Homocysteine: predictor of thrombotic disease. AB - Up to one third of primary cardiovascular and cerebrovascular thrombotic events occur in people who do not have traditional risk factors. This has led the scientific community to look for other potential reasons, i.e., predictors of these events. Numerous clinical trials have demonstrated a definite link between increased levels of homocysteine and the development of cardiovascular, cerebrovascular, and peripheral vascular disease. Hyperhomocysteinemia is caused by a disruption in normal metabolism of homocysteine by lack of nutrition, pharmaceutical agents, and by inherited or acquired disorders associated with this metabolism. Elevated levels of homocysteine promote endothelial cell damage, platelet hyperactivity, and the production of abnormal clotting factors leading to the development of thromboembolic plaques in the coronary, carotid, and peripheral vascular systems. The laboratory assessment of homocysteine has been made easier and more readily available to the clinician by the development of new enzyme immunoassay technology. Preanalytical variables, however, such as collection, processing, and storage are very important considerations for the accurate detection of elevated levels of homocysteine. PMID- 11760828 TI - High sensitivity C-reactive protein. AB - Though there is no apparent relationship between CRP and cardiovascular disease, the hsCRP may be the most effective single marker of disease among otherwise healthy adults, and is certainly an effective marker when employed in combination with other proven markers such as fibrinogen, homocysteine, and lipid assays. The hsCRP test may not be particularly useful among inpatients, however, as it is typically elevated in acute inflammatory disease. In addition to its apparent ability to predict the risk of cardiovascular disease, the hsCRP test points the way to further identification of risk markers. PMID- 11760829 TI - Reconsidering the effects of antiresorptive therapies in reducing osteoporotic fracture. AB - Concepts of what constitutes osteoporosis have evolved from the single criterion of low bone mass to a more inclusive consideration of bone strength, based on both quantity and quality. The evidence driving this shift is drawn from many sources. For example, recent studies of bone geometry have shown what engineers have always known: material properties and structural strength are inseparable. Genetic factors also argue against a one-dimensional (ID) view of osteoporosis. Large-scale family studies present a strong case for genetic influences on bone mass and predisposition to fracture. The contribution of aging to fracture risk has long been known, but we are only now beginning to understand what happens to bone remodeling and microstructure in an aging skeleton. The recognition that osteoporosis is far more complex than previously thought suggests that factors in addition to bone mineral density (BMD) may be useful for evaluating bone fragility and therapeutic effectiveness. Although assessment of BMD is noninvasive and widely available, the degree of increase in BMD alone fails to account for the broader effectiveness of antiresorptive agents in reducing the risk of fractures related to osteoporosis. Indeed, the very multiplicity of factors that determine fracture risk implies that response to therapy may be equally complex. Studies of response to antiresorptive agents and the cellular processes they induce are at best preliminary at this time. Although new technologies have been applied to studying bone microarchitecture, their invasive nature limits wide use. New methods are needed to provide insight into the causes and effects of bone fragility. The definition of osteoporosis, meanwhile, must still be considered a work in progress. PMID- 11760830 TI - Midregion parathyroid hormone-related protein inhibits growth and invasion in vitro and tumorigenesis in vivo of human breast cancer cells. AB - Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide hormone that undergoes extensive post-translational processing, and PTHrP(38-94)-amide is one of the mature secretory forms of the peptide. In this study, we explored the effect of PTHrP(38-94)-amide in a panel of six breast cancer cell lines "in vitro" and in MDA-MB231 cells "in vivo" specifically examining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38-94)-amide markedly inhibited proliferation and also caused striking toxicity and accelerated cell death in breast cancer cells. In addition, direct injection of PTHrP(38-94)-amide into MDA-MB231 breast cancer cells passaged in immunodeficient mice produced a marked reduction in tumor growth. These studies (i) indicate breast cancer cells are one of the few tissues in which specific effects of midregion PTHrP have been established to date, (ii) support a role for midregion secretory forms of PTHrP in modulating not only normal but also pathological mammary growth and differentiation, (iii) add further evidence for the existence of a specific midregion PTHrP receptor, and (iv) provide a novel molecule for modeling of small molecule analogues that may have anti-breast cancer effects. PMID- 11760831 TI - Parathyroid hormone-related protein is required for normal intramembranous bone development. AB - It is well established that parathyroid hormone-related protein (PTHrP) regulates chondrocytic differentiation and endochondral bone formation. Besides its effect on cartilage, PTHrP and its major receptor (type I PTH/PTHrP receptor) have been found in osteoblasts, suggesting an important role of PTHrP during the process of intramembranous bone formation. To clarify this issue, we examined intramembranous ossification in homozygous PTHrP-knockout mice histologically. We also analyzed phenotypic markers of osteoblasts and osteoclasts in vitro and in vivo. A well-organized branching and anastomosing pattern was seen in the wild type mice. In contrast, marked disorganization of the branching pattern of bone trabeculae and irregularly aligned osteoblasts were recognized in the mandible and in the bone collar of the femur of neonatal homozygous mutant mice. In situ hybridization showed that most of the osteoblasts along the bone surfaces of the wild-type mice and some of the irregularly aligned osteoblastic cells in the homozygous mice expressed osteocalcin. Alkaline phosphatase (ALP) activity and expression of osteopontin messenger RNA (mRNA) in primary osteoblastic cells did not show significant differences between cultures derived from the mixture of heterozygous mutant and wild-type mice (+/? mice) and those from homozygous mutant mice. However, both mRNA and protein levels of osteocalcin in the osteoblastic cells of homozygous mutant mice were lower than those of +/? mice, and exogenous PTHrP treatment corrected this suppression. Immunohistochemical localization of characteristic markers of osteoclasts and ruffled border formation did not differ between genotypes. Cocultures of calvarial osteoblastic cells and spleen cells of homozygous mutant mice generated an equivalent number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear and multinucleated cells and of pit formation to that of +/? mice, suggesting that osteoclast differentiation is not impaired in the homozygous mutant mice. These results suggest that PTHrP is required not only for the regulation of cartilage formation but also for the normal intramembranous bone development. PMID- 11760832 TI - Assessment of gene regulation by bone morphogenetic protein 2 in human marrow stromal cells using gene array technology. AB - Marrow stromal cells can differentiate into osteoblasts, adipocytes, myoblasts, and chondrocytes. Bone morphogenetic protein 2 (BMP-2) is a potent stimulator of osteoblastic differentiation, and identification of the genes regulated by BMP-2 in these cells should provide insight into the mechanism(s) of osteoblastic differentiation. Thus, we used a conditionally immortalized human marrow stromal cell line (hMS) and a gene expression microarray containing probes for a total of 6800 genes to compare gene expression in control and BMP-2-treated cultures. A total of 51 genes showed a consistent change in messenger RNA (mRNA) frequency between two repeat experiments. Seventeen of these genes showed a change in expression of at least 3-fold in BMP-2-treated cultures over control cultures. These included nuclear binding factors (10 genes), signal transduction pathway genes (2 genes), molecular transport (1 gene), cell surface proteins (2 genes) and growth factors (2 genes). Of particular interest were four of the nuclear binding factor genes ID-1, ID-2, ID-3, and ID-4. These encode dominant negative helix-loop-helix (dnHLH) proteins that lack the nuclear binding domain of the basic HLH proteins and thus have no transcriptional activity. They have been implicated in blocking both myogenesis and adipogenesis. Other transcription factors up-regulated at least 3-fold by BMP-2 included Dlx-2, HES-1, STAT1, and JunB. The changes in these nuclear binding factor mRNA levels were confirmed by real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). A further three transcription factors, core binding factor beta (CBFbeta), AREB6, and SOX4, showed changes in expression of between 2- and 3-fold with BMP-2 treatment. In summary, we have used a gene chip microarray to identify a number of BMP-2 responsive genes in hMS cells. Thus, these studies provide potential candidate genes that may induce osteoblastic differentiation or, in the case of the ID proteins, block differentiation along alternate pathways. PMID- 11760833 TI - Tissue inhibitor of metalloproteinases 1 and 2 directly stimulate the bone resorbing activity of isolated mature osteoclasts. AB - Tissue inhibitor metalloproteinases 1 (TIMP-1) and 2 have been reported to inhibit bone resorption. However, here, we report the direct action of both TIMP 1 and TIMP-2 on isolated rabbit mature osteoclasts to stimulate their bone resorbing activity at significantly lower concentrations (approximately ng/ml) than those (approximately microg/ml) required for the inhibition of bone resorption. The cell population used in this study consisted of a mature osteoclast population with >95% purity. TIMP-1 (approximately 50 ng/ml) and TIMP 2 (approximately 8-10 ng/ml) increased the pit area excavated by the isolated mature osteoclasts. The stimulatory effects of TIMPs were abolished by simultaneous addition of anti-TIMP antibodies. At higher concentrations, the stimulation of bone resorption decreased reversely to the control level. The magnitude of the stimulatory effect of TIMP-2 was more than that of TIMP-1. Metalloproteinase inhibitors such as BE16627B and R94138 could not replace TIMPs with respect to the bone-resorbing activity, suggesting that the osteoclast stimulating activity of TIMPs was independent of the inhibitory activity on matrix metalloproteinases (MMPs). TIMPs stimulated tyrosine phosphorylation of cellular proteins in the isolated mature osteoclasts. Both herbimycin A, an inhibitor of tyrosine kinases, and PD98059 and U0126, inhibitors of mitogen activated protein kinase (MAPK), completely blocked the TIMP-induced stimulation of osteoclastic bone-resorbing activity. On the plasma membrane of osteoclasts, some TIMP-2-binding proteins were detected by a cross-linking experiment. These findings show that TIMPs directly stimulate the bone-resorbing activity of isolated mature osteoclasts at their physiological concentrations and that the stimulatory action of TIMPs is likely to be independent of their activities as inhibitors of MMPs. PMID- 11760834 TI - Generation of bone-resorbing osteoclasts from B220+ cells: its role in accelerated osteoclastogenesis due to estrogen deficiency. AB - Estrogen deficiency stimulates both osteoclastic bone resorption and pre-B lymphopoiesis, the interrelationships between which remain unknown. To investigate the involvement of an increase in the number of B220+ cells in accelerated osteoclastogenesis after estrogen deficiency, we first examined whether ovariectomy (OVX) increased the frequency of clonogenic osteoclast precursors in bone marrow. The results were that after OVX, the frequency of clonogenic osteoclast precursors is increased in bone marrow, suggesting that accumulated osteoclast precursors contribute to accelerated osteoclastogenesis. Further, we found that cocultures of B220+ cells purified from bone marrow cells and stromal ST2 cells in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] gave rise to osteoclasts that can resorb bone and express calcitonin receptors. When the frequencies of clonogenic osteoclast precursors in the purified B220+ and B220- cell fractions were compared, it was found that the fractions gave rise to osteoclasts at similar frequencies, which rules out the possibility of cross contamination and suggests that the two fractions contain comparable numbers of osteoclast precursors. Furthermore, we identified cells that are positive for both tartrate-resistant acid phosphatase (TRAP) and B220, not only in cocultures of B220+ and ST2 cells, but also in freshly isolated unfractionated bone cells. Therefore, it is concluded that at least a subfraction of B220+ cells are capable of generating osteoclasts and that the increase in the number of B220+ cells caused by estrogen deficiency may contribute to accelerated bone resorption by this novel osteoclastogenesis pathway. PMID- 11760835 TI - Conditional ablation of the osteoblast lineage in Col2.3deltatk transgenic mice. AB - Two transgenic mouse lines were generated with a DNA construct bearing a 2.3 kilobase (kb) fragment of the rat alpha1 type I collagen promoter driving a truncated form of the herpes thymidine kinase gene (Col2.3Atk). Expression of the transgene was found in osteoblasts coincident with other genetic markers of early osteoblast differentiation. Mice treated with ganciclovir (GCV) for 16 days displayed extensive destruction of the bone lining cells and decreased osteoclast number. In addition, a dramatic decrease in bone marrow elements was observed, which was more severe in the primary spongiosum and marrow adjacent to the diaphyseal endosteal bone. Immunostaining for transgene expression within the bone marrow was negative and marrow stromal cell cultures developed normally in the presence of GCV until the point of early osteoblast differentiation. Our findings suggest that the early differentiating osteoblasts are necessary for the maintenance of osteoclasts and hematopoiesis. Termination of GCV treatment produced an exaggerated response of new bone formation in cortical and trabecular bone. The Col2.3deltatk mouse should be a useful model to define the interrelation between bone and marrow elements as well as a model to analyze the molecular and cellular events associated with a defined wave of osteogenesis on termination of GCV treatment. PMID- 11760836 TI - Arthrodesis of lumbar spine transverse processes using nacre in rabbit. AB - This study compares the osteogenic effects of nacre and autogenous bone grafts in a rabbit model of lumbar spine transverse process arthrodesis. A total of 15 rabbits were processed for arthrodesis between the fifth and sixth lumbar vertebrae using nacre powder mixed with autologous blood or autogenous iliac crest bone. Control rabbits were sham operated. Sample vertebrae were removed from the nacre-implanted rabbits at 2, 5, and 11 weeks postsurgery. The autogenous bone graft and sham-operated groups were processed for histological study 11 weeks postsurgery. The results for the three groups were compared at 11 weeks. The nacre-implanted samples taken at 2 weeks showed that the nacre was well tolerated by the host tissue. Endochondral bone formation was seen in the region of the dissolving nacre particles by 5 weeks. The newly formed bone formed a solid fusion between the transverse processes in one-third of the rabbits. There was still new bone formation at 11 weeks at the nacre implant site. Two thirds of the rabbits had formed a solid fusion. Light microscopy also showed new bone formation 11 weeks after the autologous bone graft. All rabbits had a solid fusion. This initial study indicates that nacre can induce spinal fusion in an acceptable percentage of cases. PMID- 11760837 TI - Identification of the calcium-sensing receptor in the developing tooth organ. AB - Calcium (Ca2+) is a critical component of tooth enamel, dentin, and the surrounding extracellular matrix. Ca2+ also may regulate tooth formation, although the mechanisms for such action are poorly understood. The Ca2+-sensing receptor (CaR) that is expressed in the parathyroid gland, kidney, bone, and cartilage has provided a mechanism by which extracellular Ca2+ can regulate cell function. Because these tissues play an important role in maintaining mineral homeostasis and because Ca2+ is hypothesized to play a crucial role in tooth formation, we determined whether the CaR was present in teeth. In this study, using immunohistochemistry, CaR protein was detected in developing porcine molars localized in the predentin (pD), early secretory-stage ameloblasts, maturation stage smooth-ended ameloblasts (SA), and certain cells in the stratum intermedium. CaR protein and messenger RNA (mRNA) were detected also in an immortalized ameloblast-like cell line (PABSo-E) using immunofluorescence, reverse-transcription polymerase chain reaction (RT-PCR), and Northern analysis. Based on the observation that the CaR is expressed in cultured ameloblasts, we determined whether increments in medium Ca2+ concentration could activate the intracellular Ca2+ signal transduction pathway. In PABSo-E cells, increasing extracellular Ca2+ in the medium from 0 (baseline) to 2.5mM or 5.0 mM resulted in an increase in intracellular Ca2+ above baseline to 534 +/- 69 nM and 838 +/- 86 nM, respectively. Taken together, these results suggest that the CaR is expressed in developing teeth and may provide a mechanism by which these cells can respond to alterations in extracellular Ca2+ to regulate cell function and, ultimately, tooth formation. PMID- 11760839 TI - Measurement of midfemoral shaft geometry: repeatability and accuracy using magnetic resonance imaging and dual-energy X-ray absorptiometry. AB - Although macroscopic geometric architecture is an important determinant of bone strength, there is limited published information relating to the validation of the techniques used in its measurement. This study describes new techniques for assessing geometry at the midfemur using magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) and examines both the repeatability and the accuracy of these and previously described DXA methods. Contiguous transverse MRI (Philips 1.5T) scans of the middle one-third femur were made in 13 subjects, 3 subjects with osteoporosis. Midpoint values for total width (TW), cortical width (CW), total cross-sectional area (TCSA), cortical cross-sectional area (CCSA), and volumes from reconstructed three-dimensional (3D) images (total volume [TV] and cortical volume [CVol]) were derived. Midpoint TW and CW also were determined using DXA (Lunar V3.6, lumbar software) by visual and automated edge detection analysis. Repeatability was assessed on scans made on two occasions and then analyzed twice by two independent observers (blinded), with intra- and interobserver repeatability expressed as the CV (CV +/- SD). Accuracy was examined by comparing MRI and DXA measurements of venison bone (and Perspex phantom for MRI), against "gold standard" measures made by vernier caliper (width), photographic image digitization (area) and water displacement (volume). Agreement between methods was analyzed using mean differences (MD +/- SD%). MRI CVs ranged from 0.5 +/- 0.5% (TV) to 3.1 +/- 3.1% (CW) for intraobserver and 0.55 +/- 0.5% (TV) to 3.6 +/- 3.6% (CW) for interobserver repeatability. DXA results ranged from 1.6 +/- 1.5% (TW) to 4.4 +/- 4.5% (CW) for intraobserver and 3.8 +/- 3.8% (TW) to 8.3 +/- 8.1% (CW) for interobserver variation. MRI accuracy was excellent for TV (3.3 +/- 6.4%), CVol (3.5 +/- 4.0%), TCSA (1.8 +/- 2.6%), and CCSA (1.6 +/- 4.2%) but not TW (4.1 +/- 1.4%) or CW (16.4 +/14.9%). DXA results were TW (6.8 +/- 2.7%) and CW (16.4 +/- 17.0%). MRI measures of geometric parameters of the midfemur are highly accurate and repeatable, even in osteoporosis. Both MRI and DXA techniques have limited value in determining cortical width. MRI may prove valuable in the assessment of surface-specific bone accrual and resorption responses to disease, therapy, and variations in mechanical loading. PMID- 11760838 TI - Preonset studies of spondyloepiphyseal dysplasia tarda caused by a novel 2-base pair deletion in SEDL encoding sedlin. AB - Spondyloepiphyseal dysplasia tarda (SEDT), an X-linked recessive skeletal disorder, presents with disproportionate short stature and "barrel-chest" deformity in affected (hemizygous) adolescent boys. In four reported families to date, mutations in a gene designated SEDL (spondyloepiphyseal dysplasia late) cosegregate with SEDT. We diagnosed SEDT in a short-stature, kyphotic 15-year-old boy because of his characteristic vertebral malformations. Clinical manifestations of SEDT were evident in at least four previous generations. A novel 2-base pair (bp) deletion in exon 5 of SEDL was found in the propositus by polymerase chain reaction (PCR) amplification and sequencing of all four coding exons. The mutation ATdel241-242 cosegregated with the kindred's skeletal disease. The deletion is adjacent to a noncanonical splice site for exon 5 but does not alter splicing. Instead, it deletes 2 bp from the coding sequence, causing a frameshift. A maternal aunt and her three young sons were investigated subsequently. Radiographs showed subtle shaping abnormalities of her pelvis and knees, suggesting heterozygosity. X-rays of the spine and pelvis of her 8-year old son revealed characteristic changes of SEDT, but her younger sons (aged 6 years and 3 years) showed no abnormalities. SEDL analysis confirmed that she and only her eldest boy had the 2-bp deletion. Molecular testing of SEDL enables carrier detection and definitive diagnosis before clinical or radiographic expression of SEDT. Although there is no specific treatment for SEDT, preexpression molecular testing of SEDL could be helpful if avoiding physical activities potentially injurious to the spine and the joints proves beneficial. PMID- 11760840 TI - Can metacarpal cortical area predict the occurrence of hip fracture in women and men over 3 decades of follow-up? Results from the Framingham Osteoporosis Study. AB - The purpose of this study was to determine if a single measurement of metacarpal cortical area could predict the subsequent risk of hip fracture over a long-term follow-up period. Thirteen hundred eighty-six women and 1014 men (mean age [+/- SD] 61 +/- 8 years) underwent posteroanterior hand radiography between 1966 and 1970 as part of the Framingham Study. Measurements of cortical bone width (external width and medullary width) were made at the midpoint of the second metacarpal with a digital caliper to the nearest 0.1 mm. Hip fracture occurrence was ascertained on all survivors through December 1995. Surprisingly, in women, there was no significant increase in hip fracture according to metacarpal cortical area measurements (per SD decrease) in either age-adjusted (hazard ratio [HR] = 1.13; 95% CI, 0.94-1.35) or multivariate-adjusted models (HR = 1.06; 95% CI, 0.88-1.27). The same results were seen when considering only those women who were > or = 65 years of age at the time of their X-ray or when considering only the first 10 years of follow-up. When the type of hip fracture was considered in women, after adjustment for other risk factors, there appeared to be an association between metacarpal cortical area and intertrochanteric fracture risk (HR = 1.24; 95% CI, 0.91-1.71) but not femoral neck fracture risk (HR = 0.93; 95% CI, 0.71-1.22). In men, the age-adjusted risk of hip fracture was increased modestly per SD decrease in metacarpal cortical area (HR = 1.38; 95% CI, 1.02 1.87), and this remained true after adjustment for potential confounders. In this prospective cohort study with up to 30 years of follow-up, metacarpal cortical area in men predicted hip fracture risk. In women, the only association between metacarpal cortical area and fracture risk was observed for intertrochanteric fractures and was not significant when adjusting for multiple potential confounders. We conclude that this peripheral measure of bone status is not a potent predictor of hip fracture over a long period of follow-up. PMID- 11760841 TI - Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss. AB - Spine fractures usually occur less commonly in men than in women. To identify the structural basis for this gender difference in vertebral fragility, we studied 1013 healthy subjects (327 men and 686 women) and 76 patients with spine fractures (26 men and 50 women). Bone mineral content (BMC), cross-sectional area (CSA), and volumetric bone mineral density (vBMD) of the third lumbar vertebral body (L3) were measured by posteroanterior (PA) and lateral scanning using dual energy X-ray absorptiometry (DXA). In this cross-sectional study, the diminution in peak vertebral body BMC from young adulthood to old age was less in men than in women (6% vs. 27%). This diminution was the net result of two opposing changes occurring concurrently throughout adult life: the removal of bone adjacent to marrow on the inner (endosteal) surface by bone resorption and the deposition of bone on the outer (periosteal) surface by bone formation. For L3, we estimated that men resorbed 3.7 g and deposited 3.1 g, producing a net loss of 0.6 g from young adulthood to old age and women resorbed 3.1 g and deposited only 1.2 g, producing a net loss of 1.9 g. Thus, based on our indirect estimates of periosteal gain and endosteal loss across life, the observed net diminution in BMC during aging was less in men than women because absolute periosteal bone formation was greater in men than women (3.1 g vs. 1.2 g) not because absolute bone resorption was less in men. On the contrary, the absolute amount of bone resorbed was greater in men than women (3.7 g vs. 3.1 g). Periosteal bone formation also increased vertebral body CSA 3-fold more in men than in women, distributing loads onto a larger CSA, so that the load imposed per unit CSA decreased twice as much in men than in women (13% vs. 5%). In men and women with spine fractures, CSA and vBMD were reduced relative to age-matched controls. However, vBMD was no different to the adjusted vBMD in age-matched controls derived assuming controls had no periosteal bone formation during aging. Thus, large amounts of bone are resorbed in men as well as in women, accounting for the age-related increase in spine fractures in both genders. Periosteal bone formation increases CSA and offsets bone loss in both genders but more greatly in men, accounting for the lower incidence of spine fractures in men than in women. We speculate that reduced periosteal bone formation, during growth or aging, may be in part responsible for both reduced vertebral size and reduced vBMD in men and women with spine fractures. Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than age-related bone loss. PMID- 11760842 TI - The biomechanical basis of vertebral body fragility in men and women. AB - The aim of this study was to quantify the biomechanical basis for vertebral fracture risk in elderly men and women. A bone is likely to fracture when the loads imposed are similar to or greater than its strength. To quantify this risk, we developed a fracture risk index (FRI) based on the ratio of the vertebral body compressive load and strength. Loads were determined by upper body weight, height, and the muscle moment arm, and strength was estimated from cross sectional area (CSA) and volumetric bone mineral density (vBMD). With loads less than the strength of the bone, the FRI remains < 1. For any given load, once bone strength diminishes due to a falling vBMD, the FRI will increase. Should FRI approach or exceed unity, structural failure of the vertebra is likely. We measured vertebral body CSA vBMD of the middle zone of third lumbar vertebra by lateral and posteroanterior (PA) scanning using dual-energy X-ray absorptiometry (DXA) and calculated vertebral compressive stress (load per unit area) in 327 healthy men and 686 healthy women and 26 men and 55 postmenopausal women with vertebral fractures. Activities that require forward bending of the upper body caused approximately 10-fold more compressive stress on the vertebra compared with standing upright. Men and women had similar peak vBMD in young adulthood. Because men have greater stature than women, the loads imposed on the vertebral body are higher (3,754 +/- 65 N vs. 3,051 +/- 31 N; p < 0.001). However, because CSA also was higher in men than women, peak load per unit CSA (stress) did not differ by gender (317.4 +/- 4.7 N/cm2 vs. 321.9 +/- 3.3 N/cm2, NS). The FRI was similar in young men and women and well below unity (0.42 +/- 0.02 vs. 0.43 +/- 0.01; NS). Gender differences emerged during aging; CSA increased in both men and women but more so in men, so load per unit area (stress) diminished but more so in men than in women. vBMD decreased in both genders but less so in men. These changes were captured in the FRI, which increased by only 21% in men and by 102% in women so that only 9% of elderly men but 26% of elderly women had an FRI > or = 1. Men and women with vertebral fractures had an FRI that was greater than or equal to unity (1.03 +/- 0.13 vs. 1.35 +/- 0.13; p < 0.05) and was 2.04 SD and 2.26 SD higher than age-matched men and women, respectively. In summary and conclusion, young men and women have a similar vBMD, vertebral stress, and FRI. During aging, CSA increases more, and vBMD decreases less in men than in women. Thus, fewer men than women are at risk for fracture because fewer men than women have these structural determinants of bone strength below a level at which the loads exceed the bone's ability to tolerate them. Men and women with vertebral fractures have FRIs that are equal to or exceed unity. The results show that a fracture threshold for vertebrae can be defined using established biomechanical principles; whether this approach has greater sensitivity and specificity than the current BMD T score of -2.5 SD is unknown. PMID- 11760843 TI - Growth hormone is permissive for skeletal adaptation to mechanical loading. AB - The Lewis dwarf (DW) rat was used as a model to test the hypothesis that growth hormone (GH) is permissive for new bone formation induced by mechanical loading in vivo. Adult female Lewis DW rats aged 6.2 +/- 0.1 months (187 +/- 18 g) were allocated to four vehicle groups (DW), four GH treatment groups at 32.5 microg/100 g body mass (DWGH1), and four GH treatment groups at 65 microg/100 g (DWGH2). Saline vehicle or GH was injected intraperitoneally (ip) at 6:30 p.m. and 6:30 a.m. before mechanical loading of tibias at 7:30 a.m. A single period of 300 cycles of four-point bending was applied to right tibias at 2.0 Hz, and magnitudes of 24, 29, 38, or 48N were applied. Separate strain gauge analyses in 5 DW rats validated the selection of loading magnitudes. After loading, double label histomorphometry was used to assess bone formation at the periosteal surface (Ps.S) and endocortical surface (Ec.S) of tibias. Comparing left (unloaded) tibias among groups, GH treatment had no effect on bone formation. Bone formation in tibias in DW rats was insensitive to mechanical loading. At the Ec.S, mechanically induced lamellar bone formation increased in the DWGH2 group loaded at 48N (p < 0.05), and no significant increases in bone formation were observed among other groups. The percentage of tibias expressing woven bone formation (Wo.B) at the Ps.S was significantly greater in the DWGH groups compared with controls (p < 0.05). We concluded that GH influences loading related bone formation in a permissive manner and modulates the responsiveness of bone tissue to mechanical stimuli by changing thresholds for bone formation. PMID- 11760844 TI - Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location. AB - Bone tissue responds to elevated mechanical loading with increased bone formation, which is triggered either directly or indirectly by the mechanical strain engendered in the bone tissue. Previous studies have shown that mechanical strain magnitude must surpass a threshold before bone formation is initiated. The objective of this study was to estimate the strain thresholds at three different locations along the ulna of adult rats. We hypothesized that the strain threshold would be greater in regions of the ulna habitually subjected to larger mechanical strains. New bone formation was measured on the periosteal and endocortical surfaces of the ulnar diaphysis in adult female rats exposed to controlled dynamic loading. Axial, compressive loading was applied daily at five different magnitudes for a period of 2 weeks. Bone formation rate (BFR) was measured, using double-label histomorphometry at the ulnar middiaphysis and at locations 3 mm proximal and 3 mm distal to the middiaphysis. Loading induced lamellar bone formation on the periosteal surface that was greater at the distal ulnar location and lower at the proximal location when compared with the middiaphysis. Likewise, peak strains on the periosteal surface were greatest distally and less proximally. There was a significant dose-response relationship between peak strain magnitude and periosteal new bone formation when the mechanically induced strain surpassed a threshold. The strain threshold varied from 1343 microstrain (mu strain) proximally to 2284 mu strain at the midshaft to 3074 mu strain distally. Unlike the periosteal response to mechanical loading, there was not a clear dose-response relationship between applied load and bone formation on the endocortical surface. Endocortical strains were estimated to be < 20% of periosteal strains and may not have been sufficient to initiate a bone formation response. Our results show that the osteogenic response on the periosteal surface of the ulna depends on peak strain level once a strain threshold is surpassed. The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower. PMID- 11760845 TI - Total body bone mineral content and tibial cortical bone measures in preschool children. AB - This study was undertaken to identify factors that influence total body bone area (TBBA), total body bone mineral content (TBBMC), and tibial cortical bone measures in 239 children aged 3-5 years. We obtained information on demographic and anthropometric characteristics and measurements of diet, physical activity, and strength. In multiple regression analysis, TBBA correlated with height (p < 0.001), weight (p < 0.001), percent body fat (p < 0.001), and calcium intake (p = 0.02). TBBMC correlated with TBBA (p < 0.001), age (p = 0.001), and weight (p = 0.02) and inversely correlated with height (p < 0.001) and percent body fat (p < 0.001). Children born preterm had lower TBBMC compared with children born at term (p = 0.02). Both periosteal and endosteal circumferences were correlated with weight (both,p < 0.001) and inversely correlated with age (p = 0.006 and p = 0.003, respectively) and percent body fat (p = 0.002 and p = 0.005 respectively). Endosteal circumference was greater and cortical bone area was lower in children born preterm compared with those born at term (both, p = 0.04). Findings of higher TBBA and lower TBBMC in children with high percent body fat indicate undermineralization of bone and suggest that obesity in preschool children may have detrimental effects on total body bone mass accretion. A smaller tibial periosteal circumference and thus cross-sectional area in children with the same weight but higher percent body fat also would lead to a biomechanical disadvantage in these children. Findings of low TBBMC and cortical bone area among children born preterm need to be confirmed in other populations. We speculate that differences in these measurements between children born preterm and at term may be caused by differences in activity. PMID- 11760846 TI - High serum retinyl esters are not associated with reduced bone mineral density in the Third National Health And Nutrition Examination Survey, 1988-1994. AB - Hypervitaminosis A is sometimes associated with abnormalities of calcium metabolism and bone mineral status. A recent study found a negative association between reported dietary vitamin A intake and bone mineral density (BMD). Some segments of the U.S. population have high fasting serum retinyl ester concentrations, a physiological marker that may reflect high and possibly excessive vitamin A intake. We examined the association between fasting serum retinyl esters and BMD in the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III), a large, nationally representative sample of the U.S. population. BMD was measured for the femoral neck, trochanter, intertrochanter, and total hip on all nonpregnant participants aged > or = 20 years; 5,790 participants also had complete data on fasting serum retinyl esters and covariates including age, body mass index (BMI), smoking, alcohol consumption, dietary supplement use, diabetes, physical activity, and, among women, parity, menopausal status, and the use of oral contraceptives or estrogen replacement therapy. The sample included non-Hispanic white, non-Hispanic black, and Mexican American men and women. We examined the association between fasting serum retinyl esters and BMD at each site, controlling for covariates with multiple linear regression. We examined the association with osteopenia and osteoporosis with multiple logistic regression. Although the prevalences of high fasting serum retinyl esters concentration and low BMD were both substantial in this sample, there were no significant associations between fasting serum retinyl esters and any measure of bone mineral status. PMID- 11760847 TI - Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia. AB - The tissue-nonspecific alkaline phosphatase (TNSALP) gene from five German family members with childhood-type hypophosphatasia (HOPS) was analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) direct sequencing method. Four novel missense mutations (T51M, R54S, L258P, and R374H) and two that had been described previously (A160T and R206W) were detected in the respective patients. Mutation A160T was detected in 3 distinct patients, and a polymorphism V505A that had been described previously was detected in the same allele as L258P mutation in 1 patient and in 2 fathers whose V505A alleles were not transmitted to the probands. No other mutations were found in 2 patients. Transient expression of the mutant proteins in COS-1 cells showed that the four novel mutations and R206W were severe alleles, whereas A160T was a moderate allele. Analysis of its enzymatic activity and genetic transmission patterns confirmed that V505A was a polymorphism. Immunoprecipitation of the transiently expressed proteins showed that levels of the 80-kDa mature form of the enzyme were diminished or absent with the severe alleles; instead, levels of high-molecular mass disulfide-linked aggregates were increased. These results suggest that in compound heterozygotes, the combination of severe and moderate alleles may combine to cause the mild phenotype seen in childhood-type HOPS. PMID- 11760848 TI - The skeletal structure of insulin-like growth factor I-deficient mice. AB - The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact. PMID- 11760849 TI - The release and activation of transforming growth factor beta2 associated with apoptosis of chick hypertrophic chondrocytes. AB - The apoptosis of hypertrophic chondrocytes at the interface between growth cartilage and invading vessels is at the center of a series of critical events in endochondral formation. We have shown that the hypertrophy and apoptosis of chick chondrocytes in culture is associated with the release and activation of transforming growth factor beta2 (TGF-beta2). Supplementation of the culture medium with agents that influenced the maintenance of hypertrophic differentiation also influenced the release of TGF-beta2. A large proportion of the TGF-beta2 released from the cells was shown to be in an active form particularly TGF-beta2 associated with the support matrix. Inhibition of apoptosis with a broad-spectrum caspase inhibitor inhibited activation of the matrix-associated TGF-beta2. However, inhibition of apoptosis did not diminish the release of TGF-beta2. Release of TGF-beta2 by chondrocytes at a late stage of their terminal differentiation and its activation in association with apoptosis may provide a mechanism controlling the processes of vascular invasion of growth cartilage and the deposition of bone matrix on nearby cartilage remnants. PMID- 11760850 TI - Activation of transforming growth factor beta in chondrocytes undergoing endochondral ossification. AB - Transforming growth factor beta (TGF-beta) has well-documented roles in chondrocyte maturation and endochondral ossification, but the mechanisms of TGF beta activation during these processes remain unclear. In this study, we analyzed TGF-beta activation in chick embryo resting, proliferating, and hypertrophic chondrocytes in culture. We found that both levels and activation of TGF-beta increased substantially with maturation. The majority of TGF-beta produced by resting cells over culture time remained latent, but a larger portion produced by proliferating and hypertrophic cells was activated with increasing maturation. Zymography of gelatin gels revealed that matrix metalloprotease 2 (MMP-2) and MMP 9 were expressed by each population and that MMP-13 characterized hypertrophic chondrocytes and to a lesser extent proliferating chondrocytes in late cultures. Treatment with pharmacologic agents revealed that both MMPs and serine proteases are involved in activation. However, because inhibition of MMPs almost completely prevented TGF-beta activation, MMPs appear crucial for activation. During culture, inclusion of the tetracycline-derived, collagenase/gelatinase inhibitor chemically modified nonantimicrobial tetracycline (CMT-8) at concentrations specific for MMP-13 inhibition resulted in complete inhibition of TGF-beta activation by proliferating and hypertrophic chondrocytes. These results show that TGF-beta production, release, and activation are regulated developmentally in chondrocytes. Our findings point to a strict mode of regulation of this potent factor to elicit diverse and highly specific effects during chondrocyte maturation and ossification. PMID- 11760851 TI - Goats as an osteopenic animal model. AB - A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats. PMID- 11760853 TI - The bone scan in osteomyelosclerosis. PMID- 11760852 TI - Apparent cure of a newborn with malignant osteopetrosis using prednisone therapy. AB - A newborn girl with hemorrhagic purpura, suspected neonatal sepsis, and pale and dry skin was lethargic with remarkable hepatosplenomegaly, convergent strabismus, severe anemia, and elevated alkaline phosphatase activity. Radiographs showed a generalized increase in bone density, small medullary cavities, sclerosis of the skull and vertebrae, transverse wavy stripes of sclerotic bone in the metaphyses, and bone-in-bone appearance in phalanges of hands and feet. On this basis, she was diagnosed with malignant infantile osteopetrosis. On the first day of life, the infant was given a blood transfusion and vitamin K (1 mg intravenously [iv]). Corticosteroid therapy was started with prednisone (2 mg/kg per day). She showed marked improvement of symptoms. On the 26th day and 42nd day of life, she received additional blood transfusions. On the 49th day, the patient was discharged and corticosteroid therapy was continued at a regimen of 5 mg/day. Subsequent blood sample analyses revealed normal values for age. At 1 year of life, a bone marrow sample showed normal white and red cell lineages. X-ray confirmed attenuation of the bone sclerosis; therefore, bone marrow transplantation (BMT) was not implemented. At the age of 1.5 years, prednisone therapy was discontinued gradually and withdrawn before the age of 2 years. Subsequent follow-up showed normalization of all radiological and hematologic parameters. At present, the patient is 3 years old and appears healthy with apparently complete regression of the disease. PMID- 11760854 TI - Treatment of an atraumatic fracture: the importance of establishing a definitive diagnosis. PMID- 11760855 TI - Perimenopausal bone loss: more than estrogen depletion. PMID- 11760856 TI - Jumping exercises are high impact. PMID- 11760857 TI - An explanatory model for Munchausen by proxy abuse. AB - OBJECTIVE: In Munchausen by proxy (MBP) abuse, a caretaker fabricates or induces illness in another person to obtain emotional gratification. In representative cases, a mother is the perpetrator and her child is the victim. In view of the limits of current explanatory models, we use personal accounts of MBP perpetrators, physicians, and family members as a window into understanding this counterintuitive behavior. METHOD: As subspecialty clinicians and consultants, we supplemented our extensive direct experience with MBP with a review of published reports of MBP located via MEDLINE and PsycINFO (1980 onward). We also examined the books devoted to the subject and incorporated personal accounts of MBP perpetrators and of family members and professionals involved with them. RESULTS: Factors contributing to the onset and continuation of MBP are the perpetrator's experiencing a particular drive (e.g., intense anger or frustration); lacking or overcoming internal inhibitions against abusive actions; and overcoming external inhibitions, such as the potential intercession of a spouse or pediatrician. As a result, the MBP parent experiences release from unpleasant emotions and a sense of renewed control. MBP behavior gains "habit strength" each time it occurs. CONCLUSIONS: Psychodynamic explanations of MBP, while favored by some authors, are inherently speculative and tend to be low in predictive value. We suggest broadening these traditional explanations by emphasizing observable behaviors and verifiable background factors. The behavioral perspective we outline helps explain how MBP behavior is learned, why it is more prevalent among mothers, and why it is so difficult for perpetrators to stop. PMID- 11760858 TI - Restricted emotional processing and somatic attribution in fibromyalgia. AB - OBJECTIVE: Medically unexplained symptoms or syndromes, such as fibromyalgia (FM), might be partly caused or sustained by a mechanism involving restricted emotional processing (REP) and the subsequent attribution of emotional arousal to somatic or syndrome-consistent causes. In this study, it was hypothesized that FM patients, compared to healthy individuals, would be higher on trait measures of REP (defensiveness and alexithymia), and would show affective-autonomic response dissociation, that is, higher standardized scores of heart rate responses than affective responses, during negative emotional stimulation. Additionally, FM patients were expected to attribute their bodily symptoms more to somatic than to psychological causes. METHOD: Emotional movie excerpts were shown to 16 female FM patients and 17 healthy women. Affective response and heart rate were monitored continuously, while symptoms and their causal attributions were measured before and after the excerpts. Repressor coping style and alexithymia were measured, along with negative affectivity and habitual attributions of somatic complaints. RESULTS: FM patients nearly all showed the relatively uncommon combination of high defensiveness and high anxiousness. Compared with healthy women FM patients were more alexithymic, showed a higher level of affective-autonomic response dissociation, and lower within-subject emotional variability. The groups showed opposite attributional patterns, with FM patients attributing symptoms less to psychological causes and more to somatic causes. There was no evidence of a shift in these attributions caused by the emotional stimuli. CONCLUSIONS: The results provide preliminary support for the hypotheses. Both at trait and at state level, FM showed restricted emotional processing on most of the parameters measured, and a high ratio of somatic to psychological symptom attribution, coupled with high negative affectivity. PMID- 11760859 TI - Childhood trauma and adult somatic preoccupation by body area among women in an internal medicine setting: a pilot study. AB - OBJECTIVE: This study was designed to explore the relationship between three types of abuse in childhood and their relationship to somatic preoccupation, in general and by body area, in adulthood. METHOD: Eighty-five women in an internal medicine clinic completed self-report measures of childhood sexual, physical, and emotional abuse as well as the Bradford Somatic Inventory. RESULTS: Using simple correlations, all three types of abuse were positively related to current somatic preoccupation. Using multiple regression analysis that included demographic variables (education and age) and the three forms of childhood abuse, only the demographic variables and sexual abuse were uniquely predictive of somatic preoccupation. To determine the relationship between childhood abuse and somatic symptoms based on body area (head, chest, stomach, throat) and fatigue, a series of multiple regression analyses were performed. The chest and throat areas were significant, but no abuse variable was uniquely predictive. CONCLUSIONS: Among females in adulthood, all studied forms of abuse in childhood appear to contribute to general somatic preoccupation, as well as specific somatic symptoms in the chest and throat areas. Sexual abuse, specifically, is a unique predictor for general somatic preoccupation, but not necessarily specific body areas. PMID- 11760860 TI - Anxiety and depression in an internal medicine resident continuity clinic: difficult diagnoses. AB - OBJECTIVE: To determine the prevalence of anxiety and depression in a residents' clinic and if these diagnoses are associated with patients being perceived as difficult, as well as how often these diagnoses are documented in the patients' charts. METHODS: This was a cross-sectional study conducted in a general internal medicine residents' clinic. A total of 135 patients were given the Primary Care Evaluation of Mental Disorders questionnaire (DSM-IIIR version) and their physicians filled out the Difficult Doctor-Patient Relationship Questionnaire after the visit. Charts were reviewed for documentation of a diagnosis of anxiety or depression. RESULTS: Major depression was present in 26 percent, dysthymia 16 percent, major depression in partial remission 9 percent, generalized anxiety disorder 13 percent, and panic disorder 7 percent. Overall, 38 percent had at least one and 21 percent had more than one diagnosis. Of patients with one psychiatric diagnosis, 9 percent were classified as difficult versus 100 percent of patients with four diagnoses. Documentation of depression was noted for 43 percent of patients with major depression but only 9 percent with an anxiety disorder. CONCLUSIONS: Anxiety and depression were very common among the patients in this clinic, and increasing numbers of diagnoses were associated with patients being classified as difficult. Residents diagnosed depressive disorders as often as practicing physicians in other studies, but anxiety less well. The high prevalence of mental disorders has implications for resident education in that they need to be prepared to care for these patients, but residents also may benefit from exposure to sites with more typical prevalences of these illnesses. PMID- 11760861 TI - How well informed are australian general practitioners about adolescent suicide? Implications for primary prevention. AB - OBJECTIVE: To investigate the extent of knowledge of Australian general practitioners (GPs) in terms of critical information about adolescent suicide. METHOD: GPs knowledge about adolescent suicide was assessed using the 39-item Adolescent Suicide Behaviour Questionnaire (ASBQ), distributed to all GPs listed on the Medical Practitioners Board register of the Australian state of Victoria. Forty-three percent of GPs (n = 1694) completed and returned the survey. RESULTS: GPs scored, on average, 71 percent of the questionnaire items correct. The mean level of incorrect and uncertain responses was 14 percent and 15 percent, respectively. However, there were wide differences in the number of correct scores between individual GPs, with some respondents scoring as few as four items correct and others as many as 38 items correct. Analysis of knowledge rates within ABSQ content domains showed that GPs were generally well informed about adolescent suicide in relation to precipitating factors, and less well informed about the remaining content domains. CONCLUSIONS: Australian GPs are, in general, moderately well informed, and are in a unique position to identify those at risk and to provide appropriate intervention (or referral). However, there is considerable variability in the accuracy of beliefs about adolescent suicide, with some GPs demonstrating excellent knowledge levels but others holding little accurate information. The extent of this variability in knowledge is a cause for concern. Findings highlight the need for ongoing education of GPs as an essential component of prevention strategies for youth suicide. PMID- 11760862 TI - Utilization of medical services and quality of life among low-income patients with generalized anxiety disorder attending primary care clinics. AB - OBJECTIVE: Anxiety disorders appear to influence morbidity and medical utilization. However, little is known about the relationship between Generalized Anxiety Disorder, quality of life, and medical utilization, especially among low income patients. The goals of this investigation were to 1) determine if low income patients with GAD utilize medical services more than patients with other Axis I diagnoses, or no psychopathology, and 2) compare the health-related quality of life of these three groups. METHOD: Participants were randomly recruited from public primary care clinics and administered intake assessments of demographics, stress, and health-related self-report questionnaires. At the end of the first year a structured psychiatric interview was administered (N = 431). Over the second year, patients (n = 360) were administered a health-related quality of life measure every three months for four assessments. Medical charts were abstracted to collect information about chronic illnesses and visits to outpatient clinics and the emergency department during the two years. RESULTS: Patients were predominantly middle-aged, low-income, uninsured African-American females. In this low-income sample, patients with GAD utilized the emergency department more and reported poorer quality of life than patients with other Axis I disorders and patients without any psychopathology. CONCLUSION: Low-income patients with GAD utilize the emergency department more and report poorer quality of life than patients with other Axis I disorders and patients without any psychopathology. Programs to identify and treat patients with GAD may yield improvements in quality of life, as well as reduce emergency department utilization. PMID- 11760863 TI - Religion and medicine III: developing a theoretical model. AB - In this third of a four-article series on religion and medicine, I describe a theoretical model to illustrate the complex pathways by which religion may influence physical health. Genetic factors, childhood training, psychological and social influences, health behaviors, and healthcare practices are discussed as part of this model. Considerable space is given to recent advances in psychoneuroimmunology and to stress-induced cardiovascular changes that demonstrate physiological pathways by which cognitive, emotional, and behavioral processes may influence susceptibility to disease and disease course. I also discuss research illustrating the important role that social support plays in moderating the physiological effects of stress and improving health outcomes. If religious beliefs and practices improve coping, reduce stress, prevent or facilitate the resolution of depression, improve social support, promote healthy behaviors, and prevent alcohol and drug abuse, then a plausible mechanism exists by which physical health may be affected. PMID- 11760864 TI - Psychiatric complications of malaria: a case report. AB - This article reviews the psychiatric complications of malaria. A case of malaria infection is described. The diagnoses, treatment, and neuropsychiatric complications of acute and chronic malaria infection are discussed. The treatment of malaria and its complications are summarized. PMID- 11760865 TI - A case of bilateral ptosis with unsteady gait: suggestibility and culture in conversion disorder. AB - We report a case of a 14-year-old girl who presented, following a sudden onset, with bilateral ptosis, gait disturbance, difficulty swallowing and loss of appetite, right hypochondriacal pain, and frontal headache. Protracted neurological and medical examinations were unremarkable; neither was precipitating psychological stresses evident. The condition, which manifest as typical conversion disorder, lasted for one year. "Treatment" involving electrical stimulation of both eyes muscles and legs with positive reassurance resolved the symptom. This case supports the view that conversion disorder, not only involves a strong element of suggestion, but also incorporates socio cultural sanctioned prescription. PMID- 11760866 TI - Complicated dual diagnosis: a case for physician involvement in addictions treatment. AB - Despite the high prevalence of substance use disorders, the prevention and treatment of such illnesses seem to receive little attention during physician training. This provides cause for concern, as physician involvement in addiction treatment has been relatively sparse. We present the case of a patient whose successful treatment likely relied upon her physicians' intensive training in each of the biological, psychological, and social aspects of her clinical presentation. The case illustrates the need for added emphasis on the assessment and treatment of addictive disorders during medical training, and for more active physician involvement in addictions treatment. PMID- 11760867 TI - Chimpanzee sign language and Darwinian continuity: evidence for a neurological continuity for language. AB - The current article addresses the empirical validity of the Cartesian view of language by first examining a sample of the results generated by over 30 years of chimpanzee sign language studies and then examining some neurological and behavioral data that accounts for the similarity between human and nonhuman communication systems. Finally an attempt will be made to propose a unified model of language that accounts for these findings and shows how the Cartesian world view has proposed a theory of language that is incomplete. PMID- 11760868 TI - Cisternal MHPG level inversely correlates with Glasgow coma scale after aneurysmal subarachnoid hemorrhage. AB - We measured the concentrations of monoamines and amino acids in the cisternal cerebrospinal fluid obtained from 15 patients after aneurysmal subarachnoid hemorrhage. Based on the Glasgow Coma Scale (GCS), the patients were divided into two conscious (GCS always 14 or better from the third post-operative day to Day 12; n = 8) and unconscious groups (n = 7). We examined the concentrations of monoamines and amino acids between the two groups and evaluated the correlation between the concentrations and the GCS at CSF sampling. The concentration of MHPG was significantly higher in the unconscious than in the conscious group from Days 4 to 12. A significant inverse correlation was observed between the MHPG concentration and the GCS (r = approximately 0.635, p < 0.0001). Measuring the cisternal MHPG concentration may be useful for estimating convalescence after subarachnoid hemorrhage. PMID- 11760869 TI - Clinical cerebral microdialysis: brain metabolism and brain tissue oxygenation after acute brain injury. AB - While continuous monitoring of brain tissue oxygenation (P(ti)O2) is known as a practicable, safe and reliable monitoring technology supplementing traditional ICP-CPP-monitoring, the impact of cerebral microdialysis, now available bedside, is not proven extensively. Therefore our studies focused on the practicability, complications and clinical impact of microdialysis during long term monitoring after acute brain injury, especially the analysis of the correlation between changes of local brain oxygenation and metabolism. Advanced neuromonitoring including ICP-CPP-p(ti)O2 was performed in 20 patients suffering from acute brain injury. Analysis of the extracellular fluid metabolites (glucose, lactate, pyruvate, glutamate) were performed bedside hourly. No catheter associated complications, like infection and bleeding, occurred. However, longterm monitoring was limited in 5 out of 20 patients caused by obliteration of the microdialysis catheter after 3-4 days. In the individual patients partly a correlation between increased lactate levels as well as lactate pyruvate ratios and hypoxic brain tissue oxygenation could be found. Analysing the data sets of all patients only a low correlation was detected indicating physiological and increased lactate and lactate/pyruvate ratio during sufficient brain oxygenation. Additionally, concentrations of excitatory amino acid glutamate were found in normal and elevated range during periods of hypoxic oxygenation (P(ti)O2 < 10 mmHg) and intracranial hypertension. Our data strongly suggest partly evidence of correlation between hypoxic oxygenation and metabolic disturbances after brain injury. On the other hand brain metabolism is altered without changes of cerebral oxygenation. Further studies are indicated to improve our pathophysiological knowledge before microdialysis is routinely useful in neurointensive care. PMID- 11760870 TI - Effects of popliteal illumination on cerebral near-infrared spectroscopy. AB - The endogenous clock of humans can be influenced by light application to the popliteal region. Previously, it had been assumed that light must fall directly into the eye in order to influence the inner circadian clock. This study, published in 1998, has not been reproduced. We investigated the effects of laser light illumination (785 nm for 5 min) on cerebral near infrared spectroscopy (NIRS) in 33 volunteers. There were significant (p < 0.001) delayed (2 min) alterations in NIRS parameters during popliteal light illumination. This could be further evidence for extraocular phototransduction in humans. PMID- 11760871 TI - Serial MRI findings in patient with chronic cryptococcus meningo-encephalitis. AB - We describe the serial changes of magnetic resonance imaging (MRI) in a patient with chronic cryptococcus meningo-encephalitis. In the subacute phase, MRI revealed a focal lesion with hyperintensity on T2-weighted image (WI) in the left thalamus. At 11 months after the onset, MRI showed a focal lesion with hyperintensity on T2-WI in the right pons that was enhanced with gadolinium (Gd). At 13 months after the onset, the lesion in the left thalamus became rim enhanced with Gd. After antifungal therapy (amphotericin B and 5-flucytosine), the rim enhancement in the left thalamus and the high signal intensity area in the right pons decreased. Cryptococcoma should be in the differential from other ring enhancing lesions. PMID- 11760872 TI - Biocompatibility evaluation of dura mater substitutes in an animal model. AB - Dura-Guard Dural Repair Patch, PRECLUDE Dura Substitute, and Codman ETHISORB Dura Patch were evaluated in a six-month dural tissue reaction study in rabbits. Bilateral craniotomy was followed by subdural implantation for each dura mater substitute. The surgical procedure for the sham control group was the same except that no material was implanted. Implantation of all of these dura mater substitutes for 28, 91, or 182 days post-implantation did not result in any deaths or clinical neurobehavioral abnormalities, changes in cerebrospinal fluid, or significant macroscopic changes at necropsy. However, histomorphologic evaluation of the implantation sites revealed some differences in the tissue response to these materials. For Dura-Guard Dural Repair Patch, a nonabsorbable material derived from bovine pericardium, the implantation site was characterized by fibrosis of the overlying area with islands of osseous metaplasia and adhesions to the brain surface. Over time, infiltrative fibrosis of the implant resulted in separation of the collagenous layers of the implant and compression of the underlying brain. Fibrosis of the overlying area that incorporated this material formed a 'replacement' dura mater. Adhesions to the brain surface observed initially were still present at six months post-implantation. Implantation of PRECLUDE Dura Substitute, a nonabsorbable material comprised of expanded polytetrafluoroethylene, resulted in virtually no early reaction, and few adhesions to the brain surface at any time period. Although this material was eventually incorporated by fibrosis, islands of osseous metaplasia were also observed in this 'replacement' dura mater. The tissue reaction to Codman ETHISORB Dura Patch, an absorbable material comprised of polyglactin 910 and polydioxanone, was generally characterized by low-grade granulomatous inflammation and initial adhesions to the brain surface. The three-dimensional structure of this implant acted as a scaffold to guide the development and integration of a 'replacement' dura mater. The absorption of the material was associated with complete resolution of the inflammatory reaction, a lack of cerebral adhesions, and restoration of the normal architecture of this region. In conclusion, subdural implantation of Dura-Guard Dural Repair Patch, PRECLUDE Dura Substitute, or Codman ETHISORB Dura Patch in rabbits for up to six months resulted in the eventual restoration of the dura mater without significant adverse effects. However, osseous metaplasia associated with nonabsorbable Dura Guard Dural Repair Patch and PRECLUDE Dura Substitute, and the infiltration of Dura-Guard Dural Repair Patch by fibrosis suggests that long-term follow-up may be needed after the use of these materials in patients. An advantage of Codman ETHISORB Dura Patch was that it was completely absorbed after guiding the restoration of the dura mater without any morphological sequelae. PMID- 11760873 TI - Gabapentin: a unique anti-epileptic agent. AB - Gabapentin is an anti-epileptic drug (AED) that was approved in 1993 for the adjunct treatment of complex partial seizures (CPS) with and without generalization. Although the mechanism of action of gabapentin has not been fully elucidated, it has been shown to be effective not only as an adjunct AED in patients with CPS, but also in children with epilepsy, many pain syndromes (most notably neuropathic pain), and several other neurological diseases. The efficacy of the drug as an AED In both adults and children has been mostly seen when used as an adjunct with other AEDs. When used as monotherapy, it has been most effective for CPS in adults at higher doses. Gabapentin as monotherapy in children has not been shown to be as beneficial as in adults. Also, the dosing of the drug in children has been complicated by negative behavioral adverse effects. Overall, gabapentin has a low incidence of adverse effects, a pharmacokinetic profile that limits its drug interactions, and limited effects on cognition when compared to traditional AEDs. The dosing of the drug is dependent on the disease state targeted, the number of specific therapeutic drugs used, and the renal function of the patient. PMID- 11760874 TI - Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy. AB - To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE. PMID- 11760875 TI - Surgical treatment of cervical intramedullary spinal cord tumors. AB - The aim of this study is to determine if radical microsurgical removal of cervical intramedullary spinal cord tumors (CIMSCT) is achievable without causing respiratory, motor and sphincter deficits. Sixteen consecutive patients, who underwent surgical removal of a cervical intramedullary spinal cord tumor between 1988 and 1997, are presented. Surgical findings and results are analyzed. Patients' pre- and postoperative neurological conditions were evaluated using the clinical/functional scale of McCormick et al. The tumor was totally removed in 15 patients (93%). An improvement in sensory and motor functionality was obtained in 10 patients (63%), five patients (31%) remained stable and only one patient (6%), in whom partial removal was performed, presented a worsening of motor and sphincter functions. None of the patients who underwent total removal have shown MR signs of recurrence. The only patient in whom a partial removal was realized, presented a bulbar diffusion of the tumor and died. Microsurgical total removal can be considered the treatment of choice for CIMSCT. An accurate dissection between tumoral mass and normal spinal cord may allow, in the majority of cases, a total removal of tumor with preservation of spinal cord. Potential alterations of the spine stability must be prevented using internal or external stabilization. PMID- 11760876 TI - Effects of iloprost on vasospasm after experimental spinal cord injury: an electron and light microscopic study. AB - It has been increasingly reported that traumatic and ischemic insults to the spinal cord may produce tissue damage through both direct and indirect mechanisms. In spite of many theories about post-traumatic spinal cord injury, there is still no satisfactory account of the exact mechanism. Vasospasm may be related to the trauma and release of vasoconstrictor or vasoactive amines. This study aims at studying the possible protective mechanisms of iloprost, a stable analogue of prostacyclin, after spinal cord injury on the rabbit. Forty-two adult male rabbits (New Zealand albino) were inflicted injuries by epidural application of an aneurysm clip to the spinal cord. Twenty-one rabbits received an i.v. infusion of 25 microg kg(-1) x h(-1) iloprost. The remaining twenty-one rabbits received an i.v. infusion of saline as the control group. Intravenous treatment started immediately after the infliction of the spinal cord injury and lasted for 1 h. Iloprost treatment had no side effects on the general physiological parameters in the rabbits. Control and iloprost treatment groups were divided into three sub-groups. The first group of animals was deeply anesthetized and spinal cords were removed 15 min after treatment. Second and third group animals were sacrificed in the 3rd and 24th hours respectively. All spinal cords were removed for light and electron microscopic examination. The width of anteriolar smooth muscle cells and the ultrastructural analysis of sulcal arterioles and venules in the ventral median fissure of spinal cords treated by iloprost revealed less thickening in all groups especially on the 24th hour group (p < 0.01), but less thickening was observed on the 3rd hour group. Iloprost-treated groups had limited edema and moderate protection of myelin and axons. These results suggest that iloprost treatment after spinal cord injury has a highly protective effect, and the possible protective effect of iloprost is resolution of vasospasm due to spinal cord injury. PMID- 11760877 TI - Vasoactive intestinal peptide influences neurite outgrowth in cultured rat spinal cord neurons. AB - Vasoactive intestinal peptide (VIP) is a neuropeptide which has been shown to exhibit a wide range of neurotrophic effects both in vivo and in vitro. For the purpose of clarifying the effect of VIP on spinal cord neurons, we studied the effect of VIP on neurite outgrowth of fetal rat ventral and dorsal portions of spinal cord in cultures. VIP-treated ventral spinal cord cultures (VSCC), compared with control VSCC, had a significant neurite outgrowth at 10(-8), 10( 6), and 10(-4) M. The effect was considered to be concentration dependent. Morphological changes of the dorsal spinal cord cultures (DSCC) remained unchanged by VIP treatment. Because of their close sequence homology with VIP, PHI-27 (peptide, histidylisoleucine amide) and secretin were also examined with the same experimental conditions as was VIP. Both PHI-27 and secretin had neurite promoting effects in VSCC at 10(-8) and 10(-6) M, respectively. However, there were no neurite promoting effects in DSCC in both of them at any concentrations. VIP had the most potent effect on neurite outgrowth in VSCC, followed by PHI-27, and secretin in their effectiveness concentrations. Our data showing VIP, PHI-27 and secretin have neurotrophic action on VSCC and suggest that a potential therapeutic use of VIP and its related peptides in treating diseases that involve degeneration and death of spinal motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis. PMID- 11760878 TI - Brain-stem abscess successfully treated by microsurgical drainage: a case report. AB - Brain-stem abscess is an uncommon condition associated with high mortality. The best method of treatment is not yet defined. It can be managed by medical treatment alone, stereotactic aspiration of the pus and medical treatment, or surgical excision/drainage of the abscess. We present a case of large brain-stem abscess, treated successfully by surgical drainage after the failure of medical treatment. The patient had a large brain-stem abscess extending from the mid brain down to the lower pons. She was in a poor neurological condition pre operatively, and was worsening despite intravenous antibiotics. The abscess was coming close to the surface in the lateral aspect of the mid-brain. The presumed source of infection was multiple dental abscesses. The brain-stem abscess was approached by a subtemporal transzygomatic approach and drained completely after making an incision on the lateral surface of the mid-brain. After the operation, the patient showed steady improvement. At six months after the surgery, the patient was fully conscious, talking fluently, and walking with the help of a walker. Her hemiparesis and co-ordination were improving. Surgical drainage of a brain-stem abscess is indicated when medical therapy fails. Proper anatomical knowledge of the brain-stem and the selection of appropriate surgical approach is important for safe drainage of the abscess. PMID- 11760879 TI - N(omega) -nitro-L-arginine methyl ester (L-NAME) attenuates the acute inflammatory responses and brain injury during the early phase of experimental Escherichia coli meningitis in the newborn piglet. AB - We evaluated the anti-inflammatory and neuroprotective effect of nonselective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli. L NAME 10 mg kg(-1) was given intravenously 30 min before induction of meningitis. L-NAME significantly attenuated the increase in intracranial pressure and decrease in cerebrospinal fluid glucose concentration observed in the meningitis group. Systemic and cerebral perfusion pressure were even higher compared to the control and meningitis groups. However, the meningitis-induced increase in tumor necrosis factor-alpha level, leukocyte numbers and lactate level in the cerebrospinal fluid was not significantly attenuated with L-NAME administration. Reduced cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were significantly improved with L-NAME treatment. Decreased brain glucose and ATP levels were also significantly improved with L-NAME treatment. These findings suggest that L-NAME was effective in attenuating the acute inflammatory responses and brain injury in neonatal bacterial meningitis. PMID- 11760880 TI - Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. AB - Although radiation injuries to the brain are well documented, immediate early histological changes in the brain remain to be defined. The present study characterizes glial injury provoked in adult rat white matter within 24 h after a single irradiation of the whole brain (10 or 20 Gray). Irradiated brains were histologically and histochemically analyzed. TUNEL-positive cells exhibiting apoptotic morphology were counted in five representative regions of the white matter. Glial cell death was further evaluated by glial cell density 24 h after irradiation, which induced both dose (p < 0.0001)- and time- (p < 0.0001) dependent apoptosis in these cells. The overall apoptotic rate in the white matter peaked within 8 h after irradiation. Total glial cell density decreased significantly in the white matter 24 h after irradiation. TUNEL-positive cells were immunohistochemically negative for GFAP, a marker for astrocytes, but positive for CNP, a marker for oligodendrocytes. The apoptotic rate was highest in the external capsule (p < 0.0001), followed by the fimbria and genu of the corpus callosum (p < 0.0001). The rates were lowest in the internal capsule and cerebellum. These data indicated that brain irradiation induces rapid apoptotic depletion of the oligodendroglial population, which may participate in the development of radiation-induced pathological conditions. PMID- 11760881 TI - Cerebral blood flow and tissue oxygen saturation in immediate and progressive ischemia in rat brain. AB - The aim of the present study was to investigate whether immediate ischemia is more harmful to the brain than progressive ischemia. To do so, we examined the correlation between the degree and the process of ischemia using hypobaric hypotension technique, which was used to reduce systemic blood pressure acutely or progressively below the lower threshold of CBF regulation, in rat brain. In Wistar rats (n = 21), global ischemia using bilateral carotid arteries occlusion coupled with hypobaric hypotension was induced by lowering mean arterial blood pressure (MABP) progressively to 55, 45 and 35 mmHg or immediately to 35 mm Hg. Local cerebral blood flow (ICBF) by laser Doppler (LD) flowmetry and tissue hemoglobin oxygen saturation (HbSO2) by a microspectrophotometric method were measured at 25 corresponding locations using a 'scanning' technique which employs a computer-controlled micromanipulator. Regional CBF (rCBF) and rHbSO2 were determined by calculation of the median value from the 25 ICBF and IHbSO2 data. In the 'progressive' group, rCBF and rHbSO2 decreased gradually and reached 12.2 +/- 15.8 LD-units and 44.9% +/- 13.4% at 35 mm Hg of MABP, respectively. In the 'immediate' group, both parameters dropped suddenly to 7.86 +/- 10.6 LD-units (p < 0.01 vs. CBF of the progressive group) and 22.5% +/- 15.5% (p < 0.001 vs. tissue HbSO2 of the progressive group) from the control at 35 mmHg. These data suggested that cerebral ischemia is better tolerated if it is induced gradually. CBF recorded by LD-scanning technique and HbSO2 value by microspectrophotometric method correlated well in the ischemic condition, indicating that HbSO2 can be preserved if CBF is decreased gradually. PMID- 11760882 TI - High-dose ketamine hydrochloride maintains somatosensory and magnetic motor evoked potentials in primates. AB - Monitoring the descending neural motor volleys (MEPs), in comparison to muscle action potentials, allows sensitive motor assessment under anesthesia irrespective of the use of muscular blockade and status of skeletal musculature. Ketamine hydrochloride (KH) had preserved muscle MEPs on a pre-established primate model. The present work examines the effect of incremental hypnotic KH dosages thoracic neural on somatosensory (SEP) and MEPs recorded epidurally in response to transcranial magnetic stimulation (TMS). Through a small thoracic T11 T12 laminotomy, an insulated double bipolar electrode was inserted epidurally and cephalad in seven cynomolgus monkeys. Thoracic spinal TMS-MEPs, and SEPs, were tested against graded increase of KH doses (0.01, 0.018, 0.032, 0.056, 0.1, and 0.18 mg kg(-1) min(-1) i.v. infusion). The direct (D-) and indirect (I-) epidural MEP peaks were well-defined under sole KH infusion. The waveforms were consistent at various dosages. At the highest cumulative dose (0.18 mg kg(-1) min(-1), total 6.5 mg kg(-1) over 150 min), I5 was host and I3 and I4 latencies were delayed. The scalp and spinal SEP showed no significant change. Recording of both neural D and I- MEPs and SEPs is feasible under high sole i.v. KH. It is the first agent to maintain up to four later I1 peaks. The reproducibility of both modalities is unquestionable under KH-based deep anesthesia. This reflects the maintenance of state of neural excitability under KH. PMID- 11760884 TI - Osteological features in pure-bred dogs predisposing to cervical spinal cord compression. AB - Relative to body size, midsagittal and interpedicular diameters of the cranial and caudal aspects of cervical vertebral foramina (C3-C7) were found to be significantly (P < 0.05) larger in small breeds than in large breeds and Dachshunds, and also larger in Dachshunds (P < 0.05) than in large breeds. This condition increases the risk for spinal cord compression resulting from relative stenosis of the cervical vertebral foramina, especially in large dogs, and this is also exacerbated by the typical shape of the vertebral foramina (i.e. dorsoventrally flattened cranially and bilaterally narrowed caudally). Within large dogs those breeds highly predisposed to cervical spinal cord compression were Great Danes (the breed with the smallest midsagittal vertebral foramen diameters from cranial C6 to cranial T1) and Doberman Pinschers, because of the most strikingly cranially dorsoventrally narrowed cone-shaped vertebral foramina at C6 and C7. The existence of a small midsagittal diameter in the cranial cervical spine was a high risk factor predisposing to spinal cord compression in small breeds and Dachshunds. Remarkable consistency was noted between the spinal level of the maximum enlargement of the spinal cord which previously was reported to be at C6, and the site of maximum enlargement of the vertebral canal currently stated in Dachshunds and small breeds. In large breeds the maximum enlargement of the vertebral canal tended to be located more caudally at the caudal limit of C7. The average age at which large dogs were most susceptible to noxious factors causing abnormal growth of the pedicles was determined to be 16 wk. PMID- 11760885 TI - Fibrocartilage at the entheses of the suprascapular (superior transverse scapular) ligament of man--a ligament spanning two regions of a single bone. AB - The suprascapular ligament converts the suprascapular notch into a foramen separating the vessels and nerve of the same name. It connects 2 regions of the same bone and does not cross any joint, and no mechanical function has yet been attributed to it. Nevertheless, variations in its thickness and length, and its tendency to ossify, suggest that the ligament responds to changes in mechanical load. This should be reflected in the composition of the extracellular matrix. The primary purpose of the present study is to demonstrate that the suprascapular ligament has fibrocartilaginous entheses (i.e. insertion sites), even though there is no obvious change in insertional angle that directly results from joint movement. Such a change is more typical of tendons or ligaments that cross highly mobile joints. The complete ligament (including both entheses) was removed from 7 cadavers shortly after death and fixed in 90% methanol. Cryosections were immunolabelled with a panel of monoclonal antibodies against collagens (types I, II, III, VI), glycosaminoglycans (chondroitin 4 sulphate, chondroitin 6 sulphate, dermatan sulphate and keratan sulphates), proteoglycans (aggrecan and versican) and link protein. Both entheses were strongly fibrocartilaginous, and a moderately fibrocartilaginous matrix was also detected throughout the remainder of the ligament. The extracellular matrix of both entheses labelled strongly for type II collagen, aggrecan and link protein. The fibrocartilaginous character of the entheses suggests that the insertion sites of the ligament are subject to both compressive and tensile loading and are regions of stress concentration. This in turn probably reflects the complex shape of the scapula and the presence of a conspicuous indentation (the suprascapular notch) near the ligament. The loading patterns may reflect either the attachment of muscles and/or the forces transmitted to the suprascapular ligament from the neighbouring coracoclavicular ligament. PMID- 11760883 TI - The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. AB - The 2 major categories of idiopathic inflammatory arthritis are rheumatoid arthritis and the seronegative spondyloarthropathies. Whilst the synovium is the primary site of joint disease in the former, the primary site in the latter is less well defined. However, it has recently been proposed that enthesitis associated changes in the spondyloarthropathies are primary and that all other joint manifestations are secondary. Nevertheless, some of the sites of disease localisation have not been adequately explained in terms of enthesitis. This article summarises current knowledge of the structure, function, blood supply, innervation, molecular composition and histopathology of the classic enthesis (i.e. the bony attachment of a tendon or ligament) and introduces the concept of 'functional' and articular 'fibrocartilaginous' entheses. The former are regions where tendons or ligaments wrap-around bony pulleys, but are not attached to them, and the latter are synovial joints that are lined by fibrocartilage rather than hyaline cartilage. We describe how these 3 types of entheses relate to other, and how all are prone to pathological changes in spondyloarthropathy. We propose that the inflammatory responses characteristic of spondyloarthropathies are triggered at these seemingly diverse sites, in genetically susceptible individuals, by a combination of anatomical factors which lead to higher levels of tissue microtrauma, and the deposition of microbes. PMID- 11760886 TI - Variations of the arterial pattern in the upper limb revisited: a morphological and statistical study, with a review of the literature. AB - A total of 192 embalmed cadavers were examined in order to present a detailed study of arterial variations in the upper limb and a meta-analysis of them. The variable terminology previously used was unified into a homogenous and complete classification, with 12 categories covering all the previously reported variant patterns of the arm and forearm. PMID- 11760887 TI - The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach. AB - The three-dimensional (3D) microanatomy of the cornea is the major determinant of its optical and mechanical properties. Scanning electron microscopy (SEM) is the most commonly used method to obtain information on the overall 3D microanatomy of organs. However, SEM has not been successful in revealing the 3D microanatomy of the cornea, because the interior of the cornea is too compact to be explored by the electron beam. In this study, the 3D organisation of the cells and extracellular materials of human and rabbit corneas was examined after exposure by HCl and NaOH digestion, and by microdissection by the adhesive tape method. In the cornea of both species, all epithelial cells exhibited microplicae regardless of their location. This raises doubts about the tear film-holding role assigned to the microplicae of the superficial cells. Human and rabbit corneas differed in the collagen fibre patterns of the epithelial basement membranes. The 3D organisation of the stromal lamellae was similar in both species. In humans and rabbits, the keratocytes showed similar 3D features. However, the surface of human keratocytes located near Descemet's membrane exhibited small fenestrations that were not present in the rabbit keratocytes. The pattern of keratocyte innervation by the stromal neural plexus and 3D keratocyte microanatomy confirms that keratocytes form a large intercommunicating network within the corneal stroma. Two morphologically discrete subpopulations of keratocytes located at different stromal levels were identified in both human and rabbit corneas, suggesting that keratocytes are not functionally homogeneous. In addition, the density of the stromal neural plexus appeared to be greater in rabbits than in humans. Clear differences between human and rabbit corneas were observed in the collagen arrangement in Descemet's membrane, which may reflect their different biomechanical requirements. PMID- 11760888 TI - The relationship of the number of Meissner's corpuscles to dermatoglyphic characters and finger size. AB - This study investigated the relationships between the density of Meissner's corpuscles and the dermatoglyphic characteristics of human fingers. Dermatoglyphic prints and tissue samples were collected from the index (II) and ring (IV) fingers of 28 cadavers from the Medical School, University of Adelaide. Pattern types, pattern intensity, total ridge count and ridge breadth, were determined for each sample and the density of Meissner's corpuscles established by recording the mean number of Meissner's corpuscles underlying a 10 mm long line on the skin surface. No relationship was found between the density of Meissner's corpuscles and pattern type, pattern intensity or total ridge count. Negative correlations were found for the density of Meissner's corpuscles with both ridge width and size of fingers. Males were found to have significantly larger fingers, larger ridge breadth, and a lower density of Meissner's corpuscles per 10 mm compared with females. However, there was no difference between the total number of Meissner's corpuscles per finger in males and females. No significant differences were found in either the density of Meissner's corpuscles between antimeres or between the index and ring fingers. These results suggest that for both the left and right hand in males and females, there is a similar number of Meissner's corpuscles for both the index and ring fingers. PMID- 11760889 TI - Thoracic splanchnic nerves: implications for splanchnic denervation. AB - Splanchnic neurectomy is of value in the management of chronic abdominal pain. It is postulated that the inconsistent results of splanchnicectomies may be due to anatomical variations in the pattern of splanchnic nerves. The advent of minimally invasive and video-assisted surgery has rekindled interest in the frequency of variations of the splanchnic nerves. The aims of this study were to investigate the incidence, origin and pattern of the splanchnic nerves in order to establish a predictable pattern of splanchnic neural anatomy that may be of surgical relevance. Six adult and 14 fetal cadavers were dissected (n = 38). The origin of the splanchnic nerve was bilaterally asymmetrical in all cases. The greater splanchnic nerve (GSN) was always present, whereas the lesser splanchnic nerve (LSN) and least splanchnic nerve (ISN) were inconsistent (LSN, 35 of 38 sides (92%); LSN, 21 of 38 sides (55%). The splanchnic nerves were observed most frequently over the following ranges: GSN, T6-9: 28 of 38 sides (73%); LSN, when present, T10-11: (10 of 35 sides (29%); and ISN, T11-12: 3 of 21 sides (14%). The number of ganglionic roots of the GSN varied between 3 and 10 (widest T4-11; narrowest, T5-7). Intermediate splanchnic ganglia, when present, were observed only on the GSN main trunk with an incidence of 6 of 10 sides (60%) in the adult and 11 of 28 sides (39%) in the fetus. The higher incidence of the origin of GSN above T5 has clinical implications, given the widely discussed technique of undertaking splanchnicectomy from the T5 ganglion distally. This approach overlooks important nerve contributions and thereby may compromise clinical outcome. In the light of these variations, a reappraisal of current surgical techniques used in thoracoscopic splanchnicectomy is warranted. PMID- 11760890 TI - Reversed palatal perforation by upper incisors in ageing blind mole-rats (Spalax ehrenbergi). AB - Blind mole-rats (Spalax ehrenbergi) are fossorial solitary rodents that present striking morphological, physiological and behavioural adaptations to the subterranean environment in which they live. Previous studies have shown that mole-rats are specialised in tooth-digging. The rapid eruption-rate of their incisors has evolved to compensate for their excessive wear by excavation. Males use their incisors more than females for digging and fighting, and their rate of incisor eruption is significantly more rapid than in females. Since mole-rats use their incisors for digging throughout the year, we suggest that continuous mechanical pressure on their oral tissues concentrated at the apical sites of the upper incisors leads to cell and tissue fatigue. We provide evidence for 5 stages of palatal perforation by the upper incisors at their apical sites, with maximum perforation characterising aged males. Interspecies comparisons with 7 other fossorial and semi-fossorial rodent species, and with beavers, which expose their incisors to enormous mechanical pressure, revealed that this palatal perforation is unique to the male mole-rat. We suggest that while the fast eruption rate of incisors in the mole-rat compensates for the rapid wear resulting from digging, evolutionary adaptation to continuous tooth-digging is still ongoing, since the physical pressure of digging at the apical sites of the upper incisors leads to tissue destruction, breakage of the palatal bone and possibly to death, as a result of maxillary inflammation. PMID- 11760891 TI - The pathophysiology of pelvic floor disorders: evidence from a histomorphologic study of the perineum and a mouse model of rectal prolapse. AB - The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain deficient in urokinase-type plasminogen activator (uPA-/-) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA-/- mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA-/- mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders. PMID- 11760893 TI - Study of axillary lymph node asymmetry in a female population. AB - We analysed a large series of axillary lymph nodes, with and without metastases following radical mastectomy for breast cancer. We found left/right asymmetry in numbers of lymph nodes, and also asymmetry of lymph node dimensions, which could have been the caused by tumoral antigenic stimulation. The distribution of hyperplastic node patterns differed significantly. PMID- 11760892 TI - Ossification in the human calcaneus: a model for spatial bone development and ossification. AB - Perichondral bone, the circumferential grooves of Ranvier and cartilage canals are features of endochondral bone development. Cartilage canals containing connective tissue and blood vessels are found in the epiphysis of long bones and in cartilaginous anlagen of small and irregular bones. The pattern of cartilage canals seems to be integral to bone development and ossification. The canals may be concerned with the nourishment of large masses of cartilage, but neither their role in the formation of ossification centres nor their interaction with the circumferential grooves of Ranvier has been established. The relationships between cartilage canals, perichondral bone and the ossification centre were studied in the calcaneus of 9 to 38-wk-old human fetuses, by use of epoxy resin embedding, three-dimensional computer reconstructions and immunhistochemistry on paraffin sections. We found that cartilage canals are regularly arranged in shells surrounding the ossification centre. Whereas most of the shell canals might be involved in the nourishment of the cartilage, the inner shell is directly connected with the perichondral ossification groove of Ranvier and with large vessels from outside. In this way the inner shell canal imports extracellular matrix, cells and vessels into the cartilage. With the so-called communicating canals it is also connected to the endochondral ossification centre to which it delivers extracellular matrix, cells and vessels. The communicating canals can be considered as inverted 'internal' ossification grooves. They seem to be responsible for both build up intramembranous osteoid and for the direction of growth and thereby for orientation of the ossication centre. PMID- 11760894 TI - Draining of a retroaortic left renal vein via the 'subcentral veins' into the inferior vena cava. PMID- 11760895 TI - The role of mechanical bowel preparation for colonic resection and anastomosis: an experimental study. AB - BACKGROUND AND AIMS: To evaluate the effect of mechanical bowel preparation (MBP) on colonic resection and anastomosis. PATIENTS AND METHODS: Mongrel dogs were divided into two groups of 20 animals each. During the preoperative period (24 h) group A was not subjected to MBP, and group B was fasted and ingested 20 ml magnesium hydroxide plus 15 ml/kg 10% mannitol orally. All animals underwent segmental colectomy followed by end-to-end anastomosis. The survivors of both groups were reoperated upon on the 7th postoperative day. RESULTS: Mortality before reoperation was significantly higher in group A (45%) than in group B (10%; P<0.05). Upon reoperation on surviving animals the incidence of localized anastomotic leakage, leakage with peritonitis, and healed anastomoses was 72.72%, 9.09%, and 18.8% in group A, and 66.66%, 22.22%, and 11.11% in group B, respectively (P>0.05). Aerobic and anaerobic bacterial cultures showed similar growth in the two groups. CONCLUSION: We conclude that the omission of MBP increased the mortality due to early anastomotic leakage with peritonitis; MBP did not change the rate of localized anastomotic leakage, leakage with peritonitis, or intact anastomoses on the 7th day; no quantitative or qualitative differences were observed in the bacteria isolated from the two groups. PMID- 11760896 TI - Study of the effect of temperature on the rectal function with evidence of thermorectal reflex. AB - BACKGROUND AND AIMS: Rectal sensation seems to originate from mechanoreceptors which are stimulated by passive rectal filling or active contraction. We investigated the effect of temperature on rectal function. PATIENTS AND METHODS: A balloon was introduced into the rectum of 28 healthy volunteers, filled with 50 ml saline at various temperatures, and rectal pressure was recorded. The test was repeated 30 min and 3 h after rectal anesthetization. RESULTS: Rectal pressure was significantly reduced at 45 degrees and 40 degrees C, showed no change at 37 degrees or 30 degrees C, and was increased at 20 degrees, 10 degrees, and 0 degrees C. At 45 degrees C patients felt rectal pain but no sensation of warmth; at 40 degrees, 37 degrees, and 30 degrees C neither rectal pain nor warm sensation was felt; at 20 degrees C or below rectal pain and cold sensation were perceived. Rectal balloon filling 30 min after anesthetization caused no significant rectal pressure changes or sensation of coldness or warmth; after 3 h, when the anesthetic had waned, the rectal pressure response and sensation were similar to those before anesthetization. CONCLUSIONS: Warm saline appears to cause rectal relaxation and cold saline rectal contraction. Subjects did not perceive sensation of warmth in the rectum but felt cold sensation, which may indicate the presence of cold receptors in the rectal wall. The rectal response to temperature variations is suggested to be reflex in nature as evidenced by its absence on rectal anesthetization. Such reflex, designated "thermorectal reflex," is proposed to mediate the rectal response and is speculated to have clinical significance in rectal dysfunctional and neurogenic disorders. PMID- 11760897 TI - Effect of caseload on the short-term outcome of colon surgery: results of a multicenter study. AB - This prospective multicenter study investigated the effect of hospital caseload on early postoperative outcome of surgery for carcinoma of the colon in 75 German hospitals and included 2293 patients. The hospitals were divided into those with a caseload of 1-30 (group A), 31-60 (group B), and more than 60 (group C) operations. Increasing caseload was associated only with fewer general postoperative complications. It was also associated with significantly greater use of antibiotic prophylaxis. No significant differences between the groups were found in resection rates, intraoperative complications, specific postoperative complications, overall postoperative morbidity, hospital mortality, or 30-day mortality. The significance of hospital caseload for the short-term postoperative outcome following surgery on the colon should not be overestimated. Basing conclusions about the results to be expected simply on the case volume is impermissible. On the basis of the available data it is not possible to establish a threshold value, that is, a minimum number of required operations. PMID- 11760898 TI - Anorectal sphincter function and rectal barostat study in patients following transanal endoscopic microsurgery. AB - BACKGROUND AND AIMS: This study evaluated the effect of transanal endoscopic microsurgery (TEM) on anorectal sphincter functions and determined the risk factors for anorectal dysfunctions (including incontinence). PATIENTS AND METHODS: A study group of 33 patients with small, mobile rectal tumors (adenoma and carcinoma) located up to 12 cm from the anal verge underwent anorectal motility studies (using pull-through anorectal manometry and rectal barostat) and endoanal ultrasound prior to surgery and 3 weeks and 6 months after TEM; controls were 20 healthy volunteers. RESULTS: Resting and squeeze anal pressures were reduced 3 weeks after TEM. Resting anal pressure remained reduced 6 months after surgery; the changes were related to low preoperative levels and to the internal anal sphincter defects rather than to the procedure duration or the type of surgery. High-pressure zone length and vector volume were decreased 3 weeks after TEM and restored 6 months later. Rectoanal inhibitory reflex, reflex sphincter contraction, rectoanal pressure gradients, threshold and maximal tolerable volume of rectal sensitivity, and compliance were significantly changed 3 weeks after TEM; only rectal wall compliance remained low at 6 months. The rectoanal inhibitory reflex, reflex sphincter contraction, rectal sensitivity, and compliance were related to the extent and type of excision (partial or full thickness). Anal ultrasound revealed internal anal sphincter defects in 29% of patients studied 3 weeks after TEM. Only 76% of patients were fully continent. Disturbed anorectal function (including partial fecal incontinence) was observed in up to 50% of patients at 3 weeks. Partial and moderate anorectal dysfunction was found in 21% patients 6 months after surgery. The main risk factors of anorectal dysfunctions following TEM included: postoperative internal anal sphincter defects, low preoperative resting anal pressure, disturbed rectoanal coordination, extent (>50% of wall circumference) and the depth (full thickness) of tumor excision. CONCLUSION: TEM has a relevant but temporary effect on anorectal motility. As a result of TEM procedures 21% of the patients had disturbed anorectal functions, mostly due to the extent or depth of tumor excision (influencing rectal compliance and rectoanal coordination), and to the sphincter defects lowering resting anal pressure. Preoperative anorectal motility studies and anal ultrasound allow the identification of patients with the risk of postoperative anorectal dysfunctions. PMID- 11760899 TI - Glucocorticoid receptor signaling in the intestinal epithelial cell lines IEC-6 and Caco-2: evidence of inhibition by interleukin-1beta. AB - BACKGROUND AND AIMS: Glucocorticoids are potent anti-inflammatory drugs widely used in the treatment of inflammatory bowel disease, but many patients do not benefit from glucocorticoid therapy (glucocorticoid resistance) or need inappropriately high doses to retain remission (glucocorticoid dependency). Because of the role of intestinal epithelial cells in inflammatory bowel disease we examined glucocorticoid receptor signaling and the effect of interleukin-1beta as one of the main proinflammatory cytokines in the intestinal epithelial cell lines IEC-6 and Caco-2. METHODS: Dexamethasone effects on transcriptional activation was measured by reporter gene assay using a construct containing glucocorticoid-responsive elements. The transrepressive effect was monitored by a nuclear factor (NF) kappaB inducible reporter construct. In addition in IEC-6 cells immuncytochemistry was used to monitor glucocorticoid receptor translocation. RESULTS: Dexamethasone induced receptor-mediated reporter gene transcription and receptor translocation, while interleukin-1beta significantly inhibited dexamethasone effects. Dexamethasone inhibited interleukin-1beta induced, NF-kappaB driven gene transcription only in IEC-6 and not in Caco-2 cells. However, in Caco-2 cells glucocorticoid receptor overexpression resulted in a marked decrease in NF-kappaB activity even in absence of dexamethasone. CONCLUSIONS: These studies demonstrate that glucocorticoid receptor driven gene regulation in intestinal epithelial cells may contribute to the anti-inflammatory effects of glucocorticoids in inflammatory bowel disease. Our data are consistent with the notion that interleukin-1beta produced during inflammatory response induces steroid resistance, which is a common clinical problem in treating patients with inflammatory bowel disease. PMID- 11760900 TI - Adaptive cytoprotection against acetic acid induced colonic injury in rats. AB - BACKGROUND AND AIMS: The phenomenon of prostaglandin dependent adaptive cytoprotection has been well established in the stomach and duodenum but not in the colon. This study investigated whether it also occurs in the colon. METHODS: Fisher rats received intracolonic administration (0.5 ml) of saline or acetic acid at low concentrations (0.01-5%) followed by high concentration (25%) at various intervals (10-720 min). The distal colon was removed 2 h after acetic acid (25%), and colonic injury was assessed macroscopically and histologically and scored. Indomethacin (5 mg/kg) or N(G)-nitro-L-arginine methyl ester (10 mg/kg) was injected intraperitoneally 1 h or 30 min before pretreatment with 1% acetic acid. RESULTS: Acetic acid (25%) administered into the colon induced 11.6+/-0.2 macroscopic scores and 10.0+/-0.4 histological scores in saline pretreated rats, which were reduced to 0.3+/-0.2 and 1.8+/-0.5 by acetic acid (1%) pretreatment, respectively. The protective effect assessed macroscopically and histologically was dose related (0.01-1% acetic acid) and long lasting (maximal at 30 min and lasting up to 6 h). Indomethacin abolished the colonic adaptive cytoprotection while nitric oxide synthase inhibitor had no effect. CONCLUSIONS: These data show that prostaglandin dependent adaptive protection is induced by exposure of the colon to low concentrations of acetic acid, suggesting that endogenous defense mechanisms are increased in the colon by mild irritants. PMID- 11760901 TI - Restoration of fecal continence with chronic electrostimulation of gracilis muscle 17 years after a Pickrell's operation. AB - A 27-year-old woman who had undergone a Pickrell's operation at the age of 10 years, was observed for severe incontinence to solid and liquid stools. Physical examination and physiological tests revealed poor resting anal tone but a very good response of the transposed gracilis to percutaneous electrostimulation, which showed that the gracilis ability to contract was maintained in spite of 17 years of only occasional and unplanned muscular activity. Examination also demonstrated that the muscle had followed body growth during the patient's development. Restoration of continence by continuous electrostimulation of the gracilis muscle was then planned. To allow muscular resistance to this stimulation a fast-to-slow twitch fiber conversion was first obtained by low frequency electrostimulation. A subcutaneous abdominal implant of a pulse generator connected to the gracilis by intramuscular platinum-iridium electrodes was carried out. After a period of muscular training, fiber conversion was achieved, and continuous electrostimulation led to complete restoration of continence with stable results at the 36 month follow-up evaluation. This case demonstrates that even such a long period of muscular inactivity does not affect the possibility of recovering a failed Pickrell's operation using electrostimulation. This easy and safe procedure can be applied to all previously failed graciloplasties provided that muscle contractility is maintained. PMID- 11760902 TI - Large lymph node metastasis gives hint to a glicentin positive small endocrine rectal carcinoma. AB - In a patient with a small endocrine carcinoma of the rectum, an unusually large lymph node metastasis was the only preoperative clinical finding. Low anterior rectal resection with total mesorectal excision and lymph node dissection was performed. The tumor demonstrated some highly unusual characteristics: it was classified as a small, low-grade neuroendocrine rectal carcinoma of L-cell type with three large lymph node metastases and morphological consistency with an endocrine tumor and focal positivity of glicentin, demonstrating a proliferation of smooth muscle cells. The established Capella classification of endocrine tumors of the rectum by morphological findings would have characterized this primary tumor as benign. In this case, however, clinical and histopathological findings more accurately reflected its malignant potential. PMID- 11760903 TI - Anorectal teratoma in an adult woman. AB - We present the case of a 21-year-old woman referred to us with the diagnosis of a pelvic mass originating in the lower rectum. Following preoperative assessment she underwent surgery from a posterior approach. The pathology of the removed mass revealed an extremely rare rectal tumor--an anorectal teratoma of the mature type. We describe the successful surgical treatment, together with radiological, microscopic and perioperative appearance. PMID- 11760904 TI - Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families. AB - Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifetime risk in gene carriers for synchronous and for metachronous colorectal cancer and endometrial cancer in women, prophylactic and extended surgery are considered as options for gene carriers. A 54-year-old patient with a history of metachronous rectal cancer and a family history fulfilling the Amsterdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histological examination of the specimen showed three synchronous colon carcinomas. The 31-year-old son carrying the pathogenic mutation refused to be included in the HNPCC surveillance program. One year later he presented with symptoms of bowel obstruction, and a carcinoma of the descending colon was diagnosed. Intraoperatively, in addition to the colon cancer, a small bowel cancer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented with synchronous cancer of the ascending colon and the lower rectum at the age of 49 years. Proctocolectomy and prophylactic hysterectomy were performed, which revealed an additional colon cancer and endometrial cancer. We discuss approaches for individual decision making for surgery in HNPCC patients. Is a subtotal colectomy indicated in the case of first colon cancer in HNPCC patients, or if the first tumor occurs in the lower rectum, should a proctocolectomy or a restorative proctocolectomy be considered? The aim of prospective clinical studies should be to assess acceptability, survival rates, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophylactic surgery. PMID- 11760905 TI - Adenocarcinoma of the appendix associated with long-standing Crohn's disease. PMID- 11760906 TI - National pharmaceutical stockpile aids homeland health security. PMID- 11760907 TI - GAO finds national plans to combat bioterrorism need improvement. PMID- 11760908 TI - Early use of interferon alfa-2a can stop HCV infection. PMID- 11760909 TI - Once-weekly erythropoiesis-stimulating protein enters market. PMID- 11760910 TI - Pharmaceutical company to pay $875 million to settle federal case. PMID- 11760911 TI - International pharmacists group convenes in Singapore. PMID- 11760912 TI - Pharmacist participation on an inpatient geriatric care team. PMID- 11760913 TI - Galantamine hydrobromide. PMID- 11760914 TI - Brinzolamide. PMID- 11760915 TI - Mometasone furoate. PMID- 11760916 TI - Achievement of anticoagulation by using a weight-based heparin dosing protocol for obese and nonobese patients. AB - The need for different heparin dosing protocols for obese and nonobese patients was studied. A chart review was performed for all patients who received heparin over an eight-month period at an acute care hospital. Data collected included age, sex, height, actual body weight (ABW), ideal body weight (IBW), initial activated partial thromboplastin time (aPTT), initial heparin bolus dose, initial heparin i.v. infusion rate, time to initial targeted aPTT, and final infusion rate. Forty patients met criteria for inclusion: 20 obese patients (greater than 30% over IBW) and 20 nonobese patients (less than 20% over IBW). Mean +/- S.D. initial heparin infusion rates for the obese and nonobese groups were 14.44+/ 1.29 and 15.04+/-0.42 units/kg/hr, respectively. Times to targeted aPTT for obese and nonobese patients were 25.86+/-12.83 and 25.18+/-14.76 hours, respectively; mean final infusion rates were 12.94+/-2.56 and 12.36+/-2.54 units/kg/hr; and percent changes from initial to final infusion rates were 11.84% and 17.76%. There were no significant differences in initial or final infusion rates or time to targeted aPTT between the two groups. It is appropriate to use ABW in a weight based heparin dosing protocol for obese patients. PMID- 11760917 TI - Mediating denials of pharmaceutical services: an alternative to traditional appeals. AB - The effectiveness of mediation as a primary tool to resolve pharmaceutical service denials by managed care is discussed. A three-month prospective randomized trial of 48 medical appeal cases involving prescription drugs was conducted by Tennessee's Department of Health. Patients whose prescription claims were denied by the state's Medicaid managed care program and whose appeals were deemed medically unnecessary by one of two independent reviewers were randomly assigned to either a standard procedure group or a mediation group. Appeals assigned to the standard procedure group were immediately referred for administrative hearing. In the mediation group, the independent reviewer assigned to the case contacted the patient's care provider, discussed the case, and recommended an alternative drug. The care provider either accepted the suggested compromise, concluding the appeals process, or declined the suggestion, allowing the appeal to go to hearing. Reviewers recorded the amount of time they spent on each appeal. The mediation did not substantially increase the time the reviewers spent on each case (mean +/- S.D. minutes, 15.83+/-7.89 mediation versus 12.26+/ 6.96 standard procedure). The mean number of appealed drugs was also similar between groups (1.46+/-0.78 mediation versus 1.35+/-0.89 standard procedure). Only 21% of appealed cases went to hearings in the mediation group, while 80% did in the standard procedure group. The average cost to the state for employing mediation ($142.92+/-$186.77) was significantly lower than the average cost incurred by using standard procedures ($355.75+/-$175.43). Mediation is an effective and efficient tool for resolving patients' appeals of denied pharmaceutical services. PMID- 11760918 TI - ASHP survey of ambulatory care responsibilities of pharmacists in managed care and integrated health systems--2001. AB - The results of a 2001 national survey of the ambulatory care responsibilities of pharmacists in managed care organizations (MCOs) and integrated health systems are reported and compared with the results of similar surveys conducted in 1997 and 1999. Three hundred and seventy-six MCOs and integrated health systems participated in the telephone survey. The surveyelicited data about organizational structure and pharmacist functions in the ambulatory care environment. Survey respondents were asked about 24 specific ambulatory care pharmacist functions. The performance of functions was related to five "enabling" factors: pharmacists on interdisciplinary care teams, automated dispensing systems, integrated electronic medical records, very supportive medical staff, and very supportive senior management. Twenty previously measured functions decreased since 1999. Decreases were greatest in negotiating pharmaceutical contracts (-28%), administering immunizations (-27%), and immunization screening (-24%). Enabling factors supported continued expansion. Two clusters of functions, patient-related and population-related activities, were identified and supported differentially by enabling factors. Group-model and staff-model HMOs had the most enabling factors and the broadest scope of pharmacist functions. Independent practice associations had fewer enabling factors and a different mix of functions, with an emphasis on population-focused functions. Ambulatory care functions of pharmacists have expanded to new areas and have decreased in more traditional areas, perhaps because of the current pharmacist shortage and the increase in the number of prescriptions and patients. PMID- 11760919 TI - Vancomycin utilization at a teaching hospital in Hong Kong. PMID- 11760920 TI - Strategies for improving pharmacy practice in Latin America. PMID- 11760921 TI - Establishing the internal and external validity of experimental studies. AB - The information needed to determine the internal and external validity of an experimental study is discussed. Internal validity is the degree to which a study establishes the cause-and-effect relationship between the treatment and the observed outcome. Establishing the internal validity of a study is based on a logical process. For a research report, the logical framework is provided by the report's structure. The methods section describes what procedures were followed to minimize threats to internal validity, the results section reports the relevant data, and the discussion section assesses the influence of bias. Eight threats to internal validity have been defined: history, maturation, testing, instrumentation, regression, selection, experimental mortality, and an interaction of threats. A cognitive map may be used to guide investigators when addressing validity in a research report. The map is based on the premise that information in the report evolves from one section to the next to provide a complete logical description of each internal-validity problem. The map addresses experimental mortality, randomization, blinding, placebo effects, and adherence to the study protocol. Threats to internal validity may be a source of extraneous variance when the findings are not significant. External validity is addressed by delineating inclusion and exclusion criteria, describing subjects in terms of relevant variables, and assessing generalizability. By using a cognitive map, investigators reporting an experimental study can systematically address internal and external validity so that the effects of the treatment are accurately portrayed and generalization of the findings is appropriate. PMID- 11760922 TI - Maintenance therapy for opioid addiction with methadone, LAAM and buprenorphine: the Emperor's New Clothes Phenomenon. PMID- 11760923 TI - Hepatitis C and substance use in a sample of homeless people in New York City. AB - This study examined the prevalence of hepatitis C virus (HCV) antibodies and its association with substance use and sexual behavior among a sample of 139 persons visiting a mobile medical clinic in Manhattan. Ninety percent were unstably housed or were living on the street. The prevalence of HCV antibodies was 32%. Prevalence was also high for hepatitis B core antibodies (47%), HIV antibodies (15%), and syphilis exposure (14%); 76% tested positive for cocaine. Among subjects who reported ever injecting (20%), 86% were HCV positive; 19% of non injectors were HCV positive. In separate multivariate logistic regression models (with injection controlled), HCV was predicted by quantitative hair assays for cocaine and self-reported duration of crack-cocaine use. Alcohol dependence and sexual behavior did not predict HCV. Hepatitis C is a significant public health problem among the urban homeless population, with injection drug use and, to a lesser extent, cocaine use implicated as risk factors. PMID- 11760924 TI - Psychiatric symptoms and HIV risk in MMPI-2 cluster subgroups of polysubstance abusers in treatment. AB - This-investigation identified personality subgroups based upon cluster analysis of MMPI-2 records of polysubstance abusers. Subgroups were compared on lifetime and current psychiatric symptoms and on attitudes and behaviors linked with HIV infection risk. High psychopathology, mild psychopathology, and subclinical MMPI 2 cluster types were identified which resemble those that have been identified in earlier studies with the original version of the MMPI. The High Psychopathology Subgroup had significantly higher proportions with all lifetime psychiatric problems (ASI), higher levels of all current psychiatric symptoms (SCL-90), and lower levels of confidence in ability to enact safer sexual practices than the Subclinical Cluster Subgroup. Fewer differences in lifetime and concurrent psychiatric symptoms were found in comparisons involving High Pathology and Mild Pathology cluster subgroups and Mild Psychopathology and Subclinical cluster subgroups. Those in the High Psychopathology Subgroup likely need treatment programs that address their more chronic and serious mental health problems and interventions that target their judgment and problem solving limitations that may increase HIV infection risk. PMID- 11760925 TI - A comparative study on schizophrenic patients with dual diagnosis. AB - As indicated in the literature, substance abuse is a significant yet complex variable in schizophrenic disorder. We evaluated hospital charts of 86 schizophrenic patients with comorbid substance use disorder and of 56 patients suffering from schizophrenia-only. We surmised that among the former group there will be a substantial proportion of patients abusing opiates and that there will be differences between schizophrenic patients abusing different drugs. Both hypotheses could be confirmed. Among our dual patients, 18 patients with alcohol, 18 patients with cannabis, and 50 patients with "hard drugs" (opiates, cocaine) use disorder were identified and several significant differences were found between the individual groups of patients in respect to basic sociodemographic and clinical variables; in particular, schizophrenic patients with alcohol use disorder (and patients suffering from schizophrenia-only) were older and better socially adjusted than schizophrenic patients with "illegal" drug use disorder. The particularities of schizophrenic patients suffering from different kinds of substance use disorder should be considered when creating individualized therapeutic programs. PMID- 11760926 TI - Polysubstance use among alcoholics. AB - Contemporary alcoholics often use multiple substances, but there is little systematic research on this. This study examines the drug use comorbidity of alcoholics (DSM diagnosis, frequency and quantity of drug use); the relationship between drinking and drug use; the relative severity of alcohol- and drug-related problems; and the validity of reports of illicit drug use. Data on substance use were collected from 248 treatment-seeking alcoholics using an expanded Time-line Follow-Back (TLFB) interview. Self-reports of substance use were validated with data from biological specimens (urine and hair). Lifetime diagnosis of joint alcohol and drug dependence/abuse was 64%. Two-thirds (68%) reported using drugs in the past 90 days: 33% powder cocaine; 29% crack cocaine; 15% heroin, and 24% cannabis. The mean proportions of exposed days on which users reported consuming a substance were 57% (alcohol), 26% (powder cocaine), 46% (crack cocaine), 47% (heroin), and 29% (cannabis). Subjects reported consuming an average of 14 standard drinks on a drinking day and $67 worth of drugs on a using day. Drug users reported drinking less than nonusers on a drinking day. Frequency of drinking and drug use were positively correlated; almost all drug users reported simultaneous drinking and drug use; and they rated drugs as the bigger problem. Considerable under-reporting of drug use occurred for the previous 3-4 days, but was more accurate for the previous month. PMID- 11760927 TI - Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM). AB - A patient undergoing management of heroin dependency with high dosages of the long-acting methadone derivative, levomethadyl acetate HCl (LAAM; ORLAAM) developed a prolonged QTc interval and polymorphic QRS complexes on EKG consistent with torsades de pointes (TdP). The patient was taking other drugs known to prolong the QTc interval (fluoxetine and IV cocaine), and those known to antagonize the activity of the P450 enzymes responsible for the metabolism of LAAM and its active metabolite (fluoxetine, cocaine and marijuana). No previous reports have appeared in the literature attributing this adverse event to LAAM therapy; however, five similar cases have been reported to the manufacturer. Animal studies indicate that LAAM and metabolites prolong the action potential duration of myocardial cells. We propose that predisposed patients on high doses of LAAM may be at risk for developing TdP. Patients being treated with LAAM should receive dosages consistent with guidelines and be evaluated for concomitant diseases, interacting drug therapies, and EKG abnormalities. PMID- 11760928 TI - The JACS study I: characteristics of a population of chemically dependent Jewish men and women. AB - In order to learn more about chemically dependent Jewish people, and to help dispel the misinformation about them, the authors surveyed individuals who were part of the JACS database. Data from 379 questionnaires were analyzed and compared with the findings of two general population surveys of Jews and a previous study of Jewish alcoholics. Seventy-one percent of respondents reported dependence on more than one substance. Alcohol was found to be the most prevalent drug of both primary (54.7%) and secondary (24.5%) dependence. The male:female ratios for all chemical dependents (1.08:1) and alcohol dependents (1:1.006) were lower than observed in national studies of American alcoholic populations, as was also found in a previous study of Jewish alcoholics. The hypotheses that alcoholic Jews suffer from lack of education, poor income, alienation or loss of religious conviction failed to be supported by the JACS study. Alcohol is the drug of choice for chemically dependent Jews. The JACS survey does not support previous ideas about causes of Jewish alcoholism. The relatively large proportion of women found deserves further study. PMID- 11760929 TI - Dopamine transporter density and novelty seeking among alcoholics. AB - OBJECTIVE: The aim of this study was to investigate a putative association between the personality trait of novelty seeking (NS) and dopaminergic neuronal activity in the human brain. METHOD: We studied the striatal dopamine transporter (DAT) density of 30 (18 early and 12 late-onset) alcoholics and 26 healthy controls with beta-CIT ([123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane) and SPET (Single Photon Emission Tomography); personality traits were assessed with the Tridimensional Personality Questionnaire (TPQ). RESULTS: DAT density correlated significantly with both NS (r = 0.46, p = 0.011) and age (r = -0.50, p = 0.005) in the alcoholics, generally. NS scores were higher in alcoholics with antisocial personality disorder (p = 0.004) than among other alcoholics. CONCLUSION: Among alcoholics, NS correlated positively with DAT density, which is in line with Cloninger's theory concerning personality and character. PMID- 11760930 TI - Michigan's unique approach to treating impaired health care professionals. AB - The practice of health care professionals impaired by alcohol or other substance abuse is an often hidden, but continuing problem. Established by law in 1994, the Michigan Health Professional Recovery Program (MHPRP) provides a new approach to treating impaired health professionals. It is unique nationally, both in its umbrella approach to most health professional licensees in the State of Michigan, and in the arrangement by which the program is run through a private contract, awarded after bidding, to five of the state's professional organizations. The arrangement maintains separation from the established professional regulatory/licensing boards unless a licensee is non-compliant. MHPRP operates under specific policies, procedures, guidelines, and criteria established by the Health Professional Recovery Committee which includes a member appointed by each health care licensing board plus two public members. As of June 30, 2000 over 1600 health care professionals in Michigan had been included in the program. PMID- 11760931 TI - Validation of publication of new names and new combinations previously effectively published outside the IJSEM. PMID- 11760932 TI - Notification that new names and new combinations have appeared in volume 51, part 5, of the IJSEM. PMID- 11760934 TI - Fusobacterium equinum sp. nov., from the oral cavity of horses. AB - Two strains of gram-negative, anaerobic, non-sporulating rod that were isolated from the normal oral cavity and oral-associated disease from horses and which phenotypically resembled Fusobacterium necrophorum were characterized by sequencing of the 16S rRNA gene, phylogenetic analysis, DNA-DNA hybridization and phenotypic characterization. The results placed the novel strains as distinct members of the genus Fusobacterium. The novel species Fusobacterium equinum sp. nov. is proposed, with strain VPB 4027T (= NCTC 13176T = JCM 11174T) as the type strain. PMID- 11760933 TI - Legionella gresilensis sp. nov. and Legionella beliardensis sp. nov., isolated from water in France. AB - Novel Legionella-like isolates, strains Montbeliard A1T and Greoux 11 D13T, isolated from two different French water sources, were studied taxonomically and phylogenetically. Morphological and biochemical characterization revealed that they were Gram-negative, aerobic, non-spore-forming bacilli with a cut-glass appearance that grew only on L-cysteine-supplemented buffered charcoal yeast extract agar. Phenotypic characterization using fatty acid and ubiquinone profiles and SDS-PAGE analysis confirmed that they were closely related, but distinct from, other species of the genus Legionella, since serotyping could not relate them to any existing serogroup. Genotypic profiles generated by randomly amplified polymorphic DNA and 16S-23S rDNA spacer region PCR analyses were unique for each of these isolates. DNA-DNA relatedness values of strains Montbeliard A1T and Greoux 11 D13T to each other and to other Legionella type strains were less than 25%. Phylogenetic affiliation of these organisms obtained by 16S rDNA sequence comparisons confirmed that they were distinct from any other known Legionella species. All the above results confirm that these strains constitute two novel species for which the names Legionella gresilensis sp. nov. (type strain Greoux 11 D13T = ATCC 700509T = CIP 106631T) and Legionella beliardensis sp. nov. (type strain Montbeliard A1T = ATCC 700512T = CIP 106632T) are proposed. PMID- 11760935 TI - Opitutus terrae gen. nov., sp. nov., to accommodate novel strains of the division 'Verrucomicrobia' isolated from rice paddy soil. AB - Three strains of obligately anaerobic bacteria were isolated from rice paddy soil microcosms. Comparative analysis of the 16S rRNA genes showed that these novel isolates have identical gene sequences and are members of the division 'Verrucomicrobia'. The novel strains are phenotypically and phylogenetically distinct from species described previously. One strain, PB90-1T, was characterized in more detail. The cells are cocci and are motile by means of a flagellum. Catalase and oxidase activities are absent. Growth-supporting substrates include mono-, di- and polysaccharides, while alcohols, amino acids and organic acids do not support growth. Propionate and acetate are the major end products of fermentation. Nitrate is reduced to nitrite, but other external electron acceptors are not utilized. The G+C content of the genomic DNA is 74 mol%. This strain represents a taxon that has not yet been formally recognized, for which the name Opitutus terrae gen. nov., sp. nov. is proposed. The type strain is PB90-1T (= DSM 11246T). PMID- 11760936 TI - Microbacterium gubbeenense sp. nov., from the surface of a smear-ripened cheese. AB - Phenotypic and phylogenetic studies were performed on 11 strains of a Microbacterium-like organism isolated from the surface of a smear-ripened cheese. The isolates were Gram-positive, catalase-positive, facultatively anaerobic, oxidase-negative, non-spore-forming, non-motile, small, slender rods and grew in 12% (w/v) NaCl. Chemotaxonomic investigation revealed that all the isolates belonged unambiguously to the genus Microbacterium. They contained type B1 peptidoglycans with L-lysine as the diamino acid and glycolyl acyl types; rhamnose and galactose were the cell wall sugars. The G+C content ranged from 69 to 72 mol%. The major menaquinones were MK-11 and MK-12 and the major fatty acids were anteiso C15:0 and C17:0 and iso C16:0. Phylogenetic analysis of the 16S rRNA sequences of four isolates showed that they represented a new subline in the genus Microbacterium, with Microbacterium barkeri as their nearest phylogenetic neighbour. M. barkeri showed the highest sequence similarity to the isolates; however, DNA-DNA hybridization showed that the isolates had only 38% chromosomal similarity to M. barkeri. Based on the phylogenetic and phenotypic distinctiveness of the isolates, it is proposed that they be classified as a new Microbacterium species, for which the name Microbacterium gubbeenense sp. nov. is suggested. The type strain has been deposited as LMG S-19263T (= NCIMB 30129T). The GenBank accession number for the 16S rDNA sequence of the type strain is AF263563. PMID- 11760937 TI - Lachnobacterium bovis gen. nov., sp. nov., a novel bacterium isolated from the rumen and faeces of cattle. AB - Phenotypic and phylogenetic analysis was performed on four strains of a previously undescribed Gram-positive, rod-shaped, anaerobic bacterium isolated from the rumen and faeces of cattle. This bacterium fermented glucose primarily to lactic acid along with minor amounts of acetic and butyric acids. The four strains produced a temperature-sensitive bacteriocin-like inhibitory substance. Comparative 16S rRNA gene sequence analysis indicated that the bacterium was a member of the clostridial XIVa cluster of the low-G+C content Gram-positive bacteria. Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be assigned to a new genus, Lachnobacterium, as Lachnobacterium bovis gen. nov., sp. nov. The type strain is YZ 87T (= ATCC BAA-151T = DSM 14045T = LRC 5382T). Its G+C content is 33.9 mol %. PMID- 11760938 TI - Phylogenetic relationships of three bacterial strains isolated from the pasture legume Biserrula pelecinus L. AB - Three bacterial strains (WSM 1283, WSM 1284, WSM 1497) isolated from root nodules of the pasture legume Biserrula pelecinus L. growing in Morocco, Italy and Greece, respectively, were studied in order to determine their phylogenetic relationship to the other members of the family Rhizobiaceae. A polyphasic approach, which included analyses of morphological and physiological characteristics, plasmid profiles, symbiotic performance and 16S rRNA gene sequencing, indicated that these strains belong to the genus Mesorhizobium. PMID- 11760939 TI - Arenibacter gen. nov., new genus of the family flavobacteriaceae and description of a new species, Arenibacter latericius sp. nov. AB - Five dark-orange-pigmented, Gram-negative, rod-shaped, non-motile, aerobic bacterial strains were isolated from sandy sediment samples collected in the South China Sea in the Indian Ocean, from a holothurian, Apostichopus japonicus, in the Sea of Japan and from a brown alga, Chorda filum, from the Sea of Okhotsk in the Pacific Ocean. Phenotypic data were collected, demonstrating that the bacteria are chemo-organotrophic and require seawater-based media for growth. Polar lipids were analysed and 27% of the total extract comprised phosphatidylethanolamine as the major component. The predominant cellular fatty acids were branched-chain saturated and unsaturated [i-C15:0, i-C15:1, a-C15:0, C15:0, C16:1(n-7)]. The DNA base composition was 37.5-38.2 mol % G+C. The level of DNA homology of the five isolates was 83-94%, indicating that these isolates belong to the same species. A 16S rDNA sequence of the type strain KMM 426T was determined and phylogenetic analysis, based on neighbour-joining and Fitch Margoliash methods, revealed that the type strain formed a distinct phyletic line in a clade corresponding to the family Flavobacteriaceae and represented a new genus. From the results of this polyphasic taxonomic analysis, it is proposed that the bacterial strains be classified in a new genus, Arenibacter gen. nov., and species, Arenibacter latericius sp. nov. The type strain is KMM 426T (VKM B 2137DT = LMG 19694T = CIP 106861T). PMID- 11760940 TI - Muricauda ruestringensis gen. nov., sp. nov., a facultatively anaerobic, appendaged bacterium from German North Sea intertidal sediment. AB - A gram-negative, facultatively anaerobic bacterium with appendages was isolated from continuous cultures with a seawater-sediment suspension containing hexadecane as the sole carbon source. Although this organism was isolated from a hexadecane-degrading bacterial community, it was not able to degrade hexadecane. However, this bacterium was able to use different sugars and amino acids for growth, indicating that it probably profits from the lysis or from products like surfactants of other cells in the community. 16S rDNA analysis demonstrated that the isolated strain is phylogenetically related to the family Flavobacteriaceae of the phylum 'Cytophaga-Flavobacterium-Bacteroides'. Evidence based on phenotypic characteristics and 16S rDNA analysis supports the conclusion that this bacterium is distinct from its nearest relative, Zobellia uliginosa (90.72% similarity in 16S rRNA gene sequence), and from the other genera of the Flavobacteriaceae. It is therefore proposed that the isolated marine bacterium represents a novel taxon, designated Muricauda ruestringensis gen. nov., sp. nov. The type strain is strain B1T (= DSM 13258T = LMG 19739T). PMID- 11760941 TI - Mycobacterium doricum sp. nov. AB - A novel mycobacterial species is described in this study. The strain was isolated from the cerebrospinal fluid of a severely immunocompromised AIDS patient. It was scotochromogenic and slow-growing. Characteristic features for its differentiation from other mycobacteria are its lipid pattern and the unique gene sequences within the hypervariable regions of the 16S rDNA. The strain shows susceptibility to current antimycobacterial drugs. The pathogenicity of the novel mycobacterium and its clinical significance are not certain, as the neurological symptoms of the patient could also be due to concomitant infection with Cryptococcus neoformans. The name Mycobacterium doricum sp. nov. is proposed for the novel mycobacterium; the type strain is strain FI-13295T (= DSM 44339T = CIP 106867T). PMID- 11760942 TI - Pseudomonas sp. strain KC represents a new genomovar within Pseudomonas stutzeri. AB - Pseudomonas sp. strain KC (= ATCC 55595 = DSM 7136) is a denitrifying aquifer isolate that produces and secretes pyridine-2,6-bis(thiocarboxylate) (PDTC), a chelating agent that fortuitously transforms carbon tetrachloride without producing chloroform. Although KC has been used successfully for full-scale bioremediation of carbon tetrachloride, its taxonomy has proven difficult to resolve, as it retains properties of both Pseudomonas stutzeri and Pseudomonas putida. In the present work, a polyphasic approach was used to conclude that strain KC represents a new genomovar (genomovar 9) within the species P. stutzeri. PMID- 11760943 TI - Detailed phylogeny of ammonia-oxidizing bacteria determined by rDNA sequences and DNA homology values. AB - A comparison of the phylogeny of 38 isolates of chemolithoautotrophic ammonia oxidizing bacteria (AOB) based on 16S rRNA gene sequences, 16S-235 rDNA intergenic spacer region (ISR) sequences and species affiliations based on DNA homology values was performed. The organisms studied all belong to the beta subclass of the Proteobacteria and included representatives of Nitrosomonas, Nitrosococcus and Nitrosospira. The similarity values of the 16S rDNA sequences were high, particularly within the Nitrosospira genus, and based on these sequences it is difficult to determine the phylogenetic position of some AOB. As an alternative and supplement to 16S rRNA gene sequencing, the ISR was sequenced and analysed phylogenetically. Due to considerably lower similarity values, the ISR-based phylogeny gives a better resolution than the phylogeny based on the functional 16S rRNA gene. Since the ISR-based phylogeny of AOB is highly consistent with the 16S rDNA based phylogeny, ISR sequencing appears as a suitable tool for resolving the detailed phylogeny of AOB. The phylogenetic position of two isolates of the former genus 'Nitrosolobus' (now included in the Nitrosospira genus) is not clear. These organisms are close relatives of the former Nitrosospira spp. and 'Nitrosovibrio' spp. (now Nitrosospira), but based on their marginal positions in the phylogenetic trees, DNA-DNA hybridization data and phenotypic characteristics, it is suggested that 'Nitrosolobus' should be a separate genus. DNA homology determination of 11 Nitrosospira isolates revealed two new species of Nitrosospira. The phylogeny of AOB reflected in the trees based on the rDNA sequences is consistent with the species affiliations of AOB by DNA homology values. This observation will probably be important for the interpretation of results from studies of natural diversity of AOB. PMID- 11760944 TI - Vibrio agarivorans sp. nov., a novel agarolytic marine bacterium. AB - It is proposed that the new Vibrio species Vibrio agarivorans accommodates two agarolytic, halophilic, fermentative bacterial strains isolated from Mediterranean sea water. The cells were gram-negative, oxidase-positive, polarly flagellated bacilli that fermented glucose without gas production and that produced no decarboxylases. They used a wide range of compounds as sole carbon and energy sources. The DNA G+C content was 44.8 mol%. Phylogenetic analysis based on complete 16S and 23S rDNA sequences revealed that the strains belong to the gamma-Proteobacteria, and are specifically related to Vibrio species. Their nearest relatives were species of the Vibrio fischeri group, sharing 16S rDNA sequence similarities below 97% with the agarolytic strains. The type strain is 289T (= CECT 5085T = DSM 13756T). PMID- 11760946 TI - Isolation of a cinnamic acid-metabolizing Clostridium glycolicum strain from oil mill wastewaters and emendation of the species description. AB - A strictly anaerobic, gram-positive, motile, sporulated bacterium, designated strain CIN5, was isolated from olive mill wastewaters after enrichment on cinnamic acid. The rod-shaped cells were slightly curved (0.4-1.1 x 2.0-15 microm) and occurred singly or in pairs. Strain CIN5 utilized a limited number of carbohydrates (glucose, fructose, maltose, sorbitol), grew optimally at 37 degrees C and at pH 7.3-7.5 and had a DNA G+C content of 29.1+/-0.3 mol%. Strain CIN5 was very closely related to Clostridium glycolicum DSM 1288T. Both strain CIN5 and the type strain of C. glycolicum transformed cinnamic acid to hydrocinnamic acid and a wide range of other cinnamic acid derivatives, including o-, m- and p-coumaric, o-, m- and p-methoxycinnamic, p-methylcinnamic, caffeic, ferulic and isoferulic acids, to their corresponding 3-phenylpropionic acids by reducing the double bond of the side chain. Glucose supplementation increased the rate of conversion markedly. The emendation of the description of C. glycolicum is proposed to include these new characteristics. PMID- 11760945 TI - Phylogenies of atpD and recA support the small subunit rRNA-based classification of rhizobia. AB - The current classification of the rhizobia (root-nodule symbionts) assigns them to six genera. It is strongly influenced by the small subunit (16S, SSU) rRNA molecular phylogeny, but such single-gene phylogenies may not reflect the evolution of the genome as a whole. To test this, parts of the atpD and recA genes have been sequenced for 25 type strains within the alpha-Proteobacteria, representing species in Rhizobium, Sinorhizobium, Mesorhizobium, Bradyrhizobium, Azorhizobium, Agrobacterium, Phyllobacterium, Mycoplana and Brevundimonas. The current genera Sinorhizobium and Mesorhizobium are well supported by these genes, each forming a distinct phylogenetic clade with unequivocal bootstrap support. There is good support for a Rhizobium clade that includes Agrobacterium tumefaciens, and the very close relationship between Agrobacterium rhizogenes and Rhizobium tropici is confirmed. There is evidence for recombination within the genera Mesorhizobium and Sinorhizobium, but the congruence of the phylogenies at higher levels indicates that the genera are genetically isolated. rRNA provides a reliable distinction between genera, but genetic relationships within a genus may be disturbed by recombination. PMID- 11760947 TI - Desulfomusa hansenii gen. nov., sp. nov., a novel marine propionate-degrading, sulfate-reducing bacterium isolated from Zostera marina roots. AB - The physiology and phylogeny of a novel sulfate-reducing bacterium, isolated from surface-sterilized roots of the marine macrophyte Zostera marina, are presented. The strain, designated P1T, was enriched and isolated in defined oxygen-free, bicarbonate-buffered, iron-reduced seawater medium with propionate as sole carbon source and electron donor and sulfate as electron acceptor. Strain P1T had a rod shaped, slightly curved cell morphology and was motile by means of a single polar flagellum. Cells generally aggregated in clumps throughout the growth phase. High CaCl2 (10 mM) and MgCl2 (50 mM) concentrations were required for optimum growth. In addition to propionate, strain P1T utilized fumarate, succinate, pyruvate, ethanol, butanol and alanine. Oxidation of propionate was incomplete and acetate was formed in stoichiometric amounts. Strain P1T thus resembles members of the sulfate-reducing genera Desulfobulbus and Desulforhopalus, which both oxidize propionate incompletely and form acetate in addition to CO2. However, sequence analysis of the small-subunit rDNA and the dissimilatory sulfite reductase gene revealed that strain P1T was unrelated to the incomplete oxidizers Desulfobulbus and Desulforhopalus and that it constitutes a novel lineage affiliated with the genera Desulfococcus, Desulfosarcina, Desulfonema and 'Desulfobotulus'. Members of this branch, with the exception of 'Desulfobotulus sapovorans', oxidize a variety of substrates completely to CO2. Strain P1T (= DSM 12642T = ATCC 700811T) is therefore proposed as Desulfomusa hansenii gen. nov., sp. nov. Strain p1T thus illustrates the difficulty of extrapolating rRNA similarities to physiology and/or ecological function. PMID- 11760948 TI - Reclassification of Saccharococcus caldoxylosilyticus as Geobacillus caldoxylosilyticus (Ahmad et al. 2000) comb. nov. AB - A polyphasic study was performed on five thermophilic strains belonging to the genus Bacillus, isolated from soil of different geographical areas. 16S rRNA gene sequence analysis placed these isolates in RNA group 5, with Saccharococcus caldoxylosilyticus and [Bacillus] thermoglucosidasius being the closest phylogenetic neighbours. The type species of Saccharococcus, Saccharococcus thermophilus, was only moderately related to these two species and the novel isolates. DNA-DNA hybridization studies and comparison of morphological, chemotaxonomic and phenotypic features supported the close relationship between the novel isolates and Saccharococcus caldoxylosilyticus. These data justify the reclassification of Saccharococcus caldoxylosilyticus. Following the transfer of the validly described Bacillus species of group 5 into the genus Geobacillus, the reclassification of Saccharococcus caldoxylosilyticus as Geobacillus caldoxylosilyticus comb. nov. is proposed. This species can be distinguished genomically from Geobacillus thermoglucosidasius, Geobacillus stearothermophilus, Geobacillus thermodenitrificans and Saccharococcus thermophilus by a specific PCR RFLP assay targeting the 16S rDNA. PMID- 11760949 TI - Agreia bicolorata gen. nov., sp. nov., to accommodate actinobacteria isolated from narrow reed grass infected by the nematode Heteroanguina graminophila. AB - Agreia bicolorata gen. nov., sp. nov. (type strain VKM Ac-1804T=UCM Ac-620T) is proposed to accommodate aerobic, oxidase- and catalase-positive, weakly motile, coryneform actinobacteria isolated from leaf galls induced by the plant-parasitic nematode Heteroanguina graminophila in narrow reed grass, Calamagrostis neglecta. Bacteria assigned to Agreia bicolorata gen. nov., sp. nov. form a distinct lineage within the phylogenetic branch of the family Microbacteriaceae and possess the following chemotaxonomic characteristics: B-type peptidoglycan containing 2,4-diaminobutyric acid, ornithine, alanine, glycine, glutamate and hydroxyglutamate; cell wall sugars rhamnose, fucose and mannose; MK-10 as major menaquinone; phosphatidylglycerol and diphosphatidylglycerol as principal phospholipids; and 12-methyltetradecanoic acid (anteiso-15:0), 14-methyl pentadecanoic acid (iso-16:0) and 14-methyl-hexadecanoic acid (anteiso-17:0) as predominant fatty acids. The DNA G+C content of Agreia bicolorata is about 67.0 mol %. PMID- 11760950 TI - Lactobacillus coleohominis sp. nov., isolated from human sources. AB - Four strains of a hitherto unrecognized gram-positive, catalase-negative, facultatively anaerobic, rod-shaped bacterium isolated from human sources were characterized using phenotypic and molecular taxonomic methods. Comparative 16S rRNA gene sequencing demonstrated that the bacterium represents a new subline within the Lactobacillus casei/Pediococcus rRNA group of the genus Lactobacillus. The unknown bacterium was readily distinguished from all other described Lactobacillus species and related taxa by biochemical tests and electrophoretic analysis of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Lactobacillus coleohominis sp. nov. The type strain of Lactobacillus coleohominis is CCUG 44007T (= CIP 106820T). PMID- 11760951 TI - Jeotgalibacillus alimentarius gen. nov., sp. nov., a novel bacterium isolated from jeotgal with L-lysine in the cell wall, and reclassification of Bacillus marinus Ruger 1983 . as mMrinibacillus marinus gen nov., comb. nov. AB - A moderately halophilic, round-endospore-forming bacterium (strain YKJ-13T) was isolated from jeotgal, a traditional Korean fermented seafood, and studied by a polyphasic taxonomic approach. This organism was related to the phylogenetic clade comprising members of Bacillus rRNA group 2 and formed a cluster with Bacillus marinus with a bootstrap fidelity value of 93.6%. The peptidoglycan type was A1alpha linked directly through L-Lys. Based on cell morphology, peptidoglycan type and phylogeny, strain YKJ-13T, together with B. marinus, is considered to be a member of Bacillus rRNA group 2. Strain YKJ-13T was also characterized by having MK-7 and MK-8 as the predominant menaquinones and iso C15:0 as the major fatty acid. The DNA G+C content was 44 mol%. Strain YKJ-13T exhibited a 16S rDNA similarity value of 95.7% with B. marinus DSM 1297T, its closest phylogenetic relative. Levels of 16S rDNA similarity between strain YKJ 13T and other Bacillus spp. were less than 94.2%. Therefore, on the basis of the data presented, the name Jeotgalibacillus alimentarius gen. nov., sp. nov. is proposed for strain YKJ-13T (= KCCM 80002T = JCM 10872T). It is also proposed that B. marinus be reclassified in Marinibacillus gen. nov. as Marinibacillus marinus comb. nov. PMID- 11760952 TI - Emended descriptions of Clostridium acetobutylicum and Clostridium beijerinckii, and descriptions of Clostridium saccharoperbutylacetonicum sp. nov. and Clostridium saccharobutylicum sp. nov. AB - On the basis of 16S rRNA gene sequencing and DNA-DNA reassociation, industrial solvent-producing clostridia have been assigned to four species. In this study, the phenotypic characteristics of Clostridium acetobutylicum, Clostridium beijerinckii, 'Clostridium saccharoperbutylacetonicum', and an unnamed Clostridium sp. represented by the strains NCP 262T and NRRL B643 are compared. In addition, a further 40 strains of solvent-producing clostridia have been classified by biotyping, DNA fingerprinting and 16S rRNA gene sequencing. These included 14 C. beijerinckii strains, two strains currently designated as 'Clostridium kaneboi' and 'Clostridium butanologenum', and 24 production strains used in the commercial acetone-butanol fermentation. All of the C. beijerinckii strains were confirmed to have been classified correctly. The 'C. kaneboi' and 'C. butanologenum' strains require reclassification as C. acetobutylicum and C. beijerinckii, respectively. The commercial production strains were found to belong either to C. beijerinckii or to the unnamed Clostridium sp. For the comparative phenotypic studies of the four species, representative strains were selected from each of the DNA-fingerprint subgroups within each species. These strains were analysed for their ability to utilize different carbohydrates, hydrolyse gelatin or aesculin, and produce indole, and were tested for the presence of catalase and urease. On the basis of these results, several phenotypic traits were found to be useful for differentiating between the four species. The descriptions of C. acetobutylicum and C. beijerinckii have been emended. The names Clostridium saccharoperbutylacetonicum sp. nov. [type strain = N1-4 (HMT) = ATCC 27021T] and Clostridium saccharobutylicum sp. nov. (type strain = DSM 13864T = ATCC BAA-117T) are proposed for the two new species. PMID- 11760953 TI - Metabolism of cinnamic acids by some Clostridiales and emendation of the descriptions of Clostridium aerotolerans, Clostridium celerecrescens and Clostridium xylanolyticum. AB - The ability of Clostridium aerotolerans DSM 5434T, Clostridium celerecrescens DSM 5628T, Clostridium methoxybenzovorans DSM 12182T, Clostridium stercorarium ATCC 35414T, Clostridium subterminale DSM 2636, Clostridium termitidis DSM 5398T, Clostridium thermolacticum DSM 2910T, Clostridium thermopalmarium DSM 5974T and Clostridium xylanolyticum DSM 6555T to metabolize cinnamic acid and various derivatives, with or without glucose supplementation, was examined. Only C aerotolerans DSM 5434T and C. xylanolyticum DSM 6555T, closely related species, transformed cinnamic acid to 3-phenylpropionic acid. Both species also reduced a wide range of cinnamic acid derivatives, including o-, m- and p-coumaric, o-, m- and p-methoxycinnamic, p-methylcinnamic, caffeic, ferulic, isoferulic and 3,4,5 trimethoxycinnamic acids to their corresponding 3-phenylpropionic acid derivatives. C. aerotolerans DSM 5434T, however, also decarboxylated p-coumaric acid into 4-vinylphenol, which was then reduced to 4-ethylphenol. C. celerecrescens was grouped with C. aerotolerans and C. xylanolyticum in subcluster XIVa of the Clostridiales. C. celerecrescens DSM 5628T only metabolized m- and p-methoxycinnamic and p-methylcinnamic acids to their corresponding 3-phenylpropionic acid derivatives, reducing the double bond in the C3 aliphatic side chain. Addition of glucose markedly increased the yield of the biotransformations by these three species. An emendation of the descriptions of C. aerotolerans, C. celerecrescens and C. xylanolyticum is proposed, based on these observations. PMID- 11760954 TI - Comparative sequence analysis of a recA gene fragment brings new evidence for a change in the taxonomy of the Lactobacillus casei group. AB - The taxonomic positions of species of the Lactobacillus casei group have been evaluated by sequencing and phylogenetic analysis of a 277 bp recA gene fragment. High sequence similarity between strain ATCC 393T, currently designated as the type strain of L. casei, and the type strain of Lactobacillus zeae, LMG 17315T, has been established, while L. casei ATCC 334 and Lactobacillus paracasei NCDO 151T form a single phylogenetic group. The taxonomic status of species and strains at issue is discussed. PMID- 11760955 TI - Phylogenetic analysis of the genus Actinoplanes and transfer of Actinoplanes minutisporangius Ruan et al. 1986 and 'Actinoplanes aurantiacus' to Cryptosporangium minutisporangium comb. nov. and Cryptosporangium aurantiacum sp. nov. AB - The phylogenetic structure of the genus Actinoplanes was determined by comparative 16S rDNA sequence analysis of the type strains of all validly described Actinoplanes species and other strains of Actinoplanes. Actinoplanes minutisporangius IFO 15962T and 'Actinoplanes aurantiacus' IFO 13967 were placed outside the family Micromonosporaceae and appeared to be closely related to the genus Cryptosporangium. On the basis of their morphological and chemotaxonomic characteristics and phylogenetic analysis, these strains were reclassified into the genus Cryptosporangium. DNA-DNA hybridization revealed that these strains differed from the species previously described in this genus. Therefore, the transfer is proposed of Actinoplanes minutisporangius Ruan et al. 1986 and 'Actinoplanes aurantiacus' IFO 13967 to the genus Cryptosporangium as Cryptosporangium minutisporangium comb. nov. and Cryptosporangium aurantiacum sp. nov. PMID- 11760956 TI - Nocardia ignorata sp. nov. AB - An isolate that was received during a mycobacterial quality control test and which was thought to be a Mycobacterium species was subjected to a polyphasic taxonomic study after mycolic acid analysis showed that it possessed mycolates characteristic of the nocardiae. Further chemotaxonomic and 16S rRNA gene sequence analyses of this isolate demonstrated that it belongs to the genus Nocardia. 16S rRNA gene sequence data, DNA-DNA hybridization studies and the biochemical characteristics of the isolate indicate that it belongs to a novel species that differs from previously described members of the genus Nocardia. The name Nocardia ignorata sp. nov. is proposed for this isolate with the type strain IMMIB R-1434T (= DSM 44496T = NRRL B-24141T). PMID- 11760957 TI - Alcalilimnicola halodurans gen. nov., sp. nov., an alkaliphilic, moderately halophilic and extremely halotolerant bacterium, isolated from sediments of soda depositing Lake Natron, East Africa Rift Valley. AB - An alkaliphilic, halotolerant, Gram-negative, heterotrophic, aerobic and rod shaped organism was isolated from drying soda and at a water-covered site of Lake Natron, Tanzania, by means of the most-probable-number technique developed for anoxygenic, phototrophic sulfur bacteria. It had an absolute requirement for alkalinity, but not for salinity; growth occurred at salt concentrations of 0-28% (w/v), with optimal growth at 3-8% (w/v) NaCl. The bacterium preferentially metabolized volatile fatty acids and required vitamins for growth. The name Alcalilimnicola halodurans gen. nov., sp. nov. is proposed for the novel isolate, placed in the gamma-Proteobacteria within the family Ectothiorhodospiraceae on the basis of analysis of the 16S rDNA sequence, polar lipids, fatty acids and DNA base composition. Although Alcalilimnicola halodurans is closely related to the extreme anoxygenic, phototrophic sulfur bacteria of the genus Halorhodospira, it is not phototrophic. PMID- 11760958 TI - Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila. AB - The genera Anaplasma, Ehrlichia, Cowdria, Neorickettsia and Wolbachia encompass a group of obligate intracellular bacteria that reside in vacuoles of eukaryotic cells and were previously placed in taxa based upon morphological, ecological, epidemiological and clinical characteristics. Recent genetic analyses of 16S rRNA genes, groESL and surface protein genes have indicated that the existing taxa designations are flawed. All 16S rRNA gene and groESL sequences deposited in GenBank prior to 2000 and selected sequences deposited thereafter were aligned and phylogenetic trees and bootstrap values were calculated using the neighbour joining method and compared with trees generated with maximum-probability, maximum-likelihood, majority-rule consensus and parsimony methods. Supported by bootstrap probabilities of at least 54%, 16S rRNA gene comparisons consistently clustered to yield four distinct clades characterized roughly as Anaplasma (including the Ehrlichia phagocytophila group, Ehrlichia platys and Ehrlichia bovis) with a minimum of 96.1% similarity, Ehrlichia (including Cowdria ruminantium) with a minimum of 97.7% similarity, Wolbachia with a minimum of 95.6% similarity and Neorickettsia (including Ehrlichia sennetsu and Ehrlichia risticii) with a minimum of 94.9% similarity. Maximum similarity between clades ranged from 87.1 to 94.9%. Insufficient differences existed among E. phagocytophila, Ehrlichia equi and the human granulocytic ehrlichiosis (HGE) agent to support separate species designations, and this group was at least 98.2% similar to any Anaplasma species. These 16S rRNA gene analyses are strongly supported by similar groESL clades, as well as biological and antigenic characteristics. It is proposed that all members of the tribes Ehrlichieae and Wolbachieae be transferred to the family Anaplasmataceae and that the tribe structure of the family Rickettsiaceae be eliminated. The genus Anaplasma should be emended to include Anaplasma (Ehrlichia) phagocytophila comb. nov. (which also encompasses the former E. equi and the HGE agent), Anaplasma (Ehrlichia) bovis comb. nov. and Anaplasma (Ehrlichia) platys comb. nov., the genus Ehrlichia should be emended to include Ehrlichia (Cowdria) ruminantium comb. nov. and the genus Neorickettsia should be emended to include Neorickettsia (Ehrlichia) risticii comb. nov. and Neorickettsia (Ehrlichia) sennetsu comb. nov. PMID- 11760959 TI - Candida thermophila sp. nov., a novel thermophilic yeast isolated from soil. AB - Yeast strain Y94T, which is capable of growth at high temperature, was isolated from soil in Korea. Characteristics of the strain include asexual reproduction by multilateral budding, the absence of extracellular starch-like compounds, a negative Diazonium blue B colour reaction, and the absence of arthrospores, ballistoconidia and ascospores; the strain can therefore be placed in the genus Candida. A maximum growth temperature of 50-51 degrees C, along with certain other physiological characteristics, and a unique 26S rDNA partial sequence separate this strain from other ascomycetous yeasts. Taken together, these results suggest that the strain is a novel species and the name Candida thermophila sp. nov. (type strain is Y94T = JCM 10994T = KCCM 50661T) is proposed. PMID- 11760960 TI - Candida bituminiphila, a novel anamorphic species of yeast. AB - A novel anamorphic species of yeast belonging to the genus Candida was isolated from tar in Canada. Morphological and physiological observations, as well as phylogenetic analyses, were performed. Conidiophores were produced, were usually short and had sympodial growth, numerous bud scars and a rachis-like structure. They bore one or more conidia. Pseudomycelium was scarcely produced and true mycelium was sparse. No sexual reproduction was observed on corn meal, malt, Gorodkowa, Dextrose Yeast Peptone or V8 agars. Zygoascus hellenicus was physiologically the most closely related species, but it differed from the novel species by its ability to assimilate D-galacturonate and L-rhamnose, ferment sucrose and grow at 37 degrees C. From sequence analysis of the 26S rDNA D1/D2 region, Z. hellenicus and Candida bertae var. bertae were the closest species with 54 and 56 bp substitutions, respectively. Similar results have been obtained from analysis of the 18S rDNA. All these data support the hypothesis that the yeast, named Candida bituminiphila, is a novel species closely related to Z. hellenicus. The holotype and only isolate of C. bituminiphila is strain CBS 8813T (= MUCL 41424T). PMID- 11760961 TI - Phylogenetic analysis of strains originally assigned to Bullera variabilis: descriptions of Bullera pseudohuiaensis sp. nov., Bullera komagatae sp. nov. and Bullera pseudoschimicola sp. nov. AB - Twenty strains previously assigned to the species Bullera variabilis Nakase & Suzuki were reclassified using a molecular taxonomic approach. The strains were regrouped first by nucleotide sequence comparison of the rDNA internal transcribed spacer (ITS) regions, including the 5.8S gene. Phylogenetic positions of B. variabilis strains with different ITS region sequences were then analysed based on their 18S rDNA sequences. The taxonomic status of the original Bullera variabilis strains was clarified further by DNA-DNA hybridization experiments. Of the 20 strains studied, five remained in the species B. variabilis, six strains were reassigned to the species Bullera mrakii and three novel species were proposed for eight of the nine remaining strains, namely Bullera pseudohuiaensis sp. nov. (one strain; type strain JCM 5984T = AS 2.2203T), Bullera komagatae sp. nov. (one strain; type strain JCM 5983T = AS 2.2202T) and Bullera pseudoschimicola sp. nov. (six strains; type strain JCM 391ST = AS 2.2201T). The remaining strain, JCM 6140, was closely related to B. pseudoschimicola. However, differences in ITS region sequences between strain JCM 6140 and strains of B. pseudoschimicola, and the intermediate DNA-DNA relatedness to representative strains of B. pseudoschimicola did not allow a definite taxonomic decision to be made for strain JCM 6140. PMID- 11760962 TI - Three new species of Saccharomyces sensu lato van der Walt from Yaku Island in Japan: Saccharomyces naganishii sp. nov., Saccharomyces humaticus sp. nov. and Saccharomyces yakushimaensis sp. nov. AB - Three new yeast species were isolated from soil and partially decayed leaves in Yaku Island and Iriomote Island in the Nansei Islands of Japan. Based on DNA hybridization and physiological characters, these represent novel taxa. These are designated Saccharomyces naganishii sp. nov. (type strain IFO 10181T = CBS 8797T), Saccharomyces humaticus sp. nov. (type strain IFO 10673T = CBS 8893T) and Saccharomyces yakushimaensis sp. nov. (type strain IFO 1889T = CBS 8894T). The phylogenetic relationships of the three new species with members of other ascomycetous genera (e.g. Kluyveromyces, Saccharomyces, Torulaspora and Zygosaccharomyces) were estimated by 18S rDNA gene sequence analysis. PMID- 11760963 TI - Reclassification of the Cryptococcus humicola complex. AB - Ten strains of the Cryptococcus humicola complex were reclassified on the basis of sequence analyses of 18S rDNA and internal transcribed spacer regions and DNA DNA reassociation experiments. They were differentiated into seven species including C humicola. Five novel species are proposed: Cryptococcus daszewskae sp. nov. (type strain CBS 5123T = JCM 11166T = MUCL 30649T), Cryptococcus fragicola sp. nov. (type strain JCM 1530TT = CBS 88981), Cryptococcus longus sp. nov. (type strain CBS 5920T = JCM 11167T = MUCL 30690T), Cryptococcus musci sp. nov. (type strain JCM 1531T = CBS 8899T) and Cryptococcus pseudolongus sp. nov. (type strain JCM 9712T = CBS 8297T). A syntype of Sporobolomyces albidus JCM 1460T is also revealed to be a distinct species; the name Cryptococcus ramirezgomezianus nom. nov. is therefore proposed for Sporobolomyces albidus Ramirez Gomez (type strain IJFM 502T = CBS 2839T = JCM 1460T = NRRL Y-2478T), since the name Cryptococcus albidus (Saito) C. E. Skinner has already been recognized for a distinct species within the genus Cryptococcus. Strains possessing either Q-9 or Q-10 have been reported to occur in C. humicola; however, after reclassification, the ubiquinone type of the species in each phylogenetic group was shown to be uniform, indicating that it is a useful criterion for the taxonomy of the Trichosporonales. PMID- 11760964 TI - New insights into the phylogenetic position of diplonemids: G+C content bias, differences of evolutionary rate and a new environmental sequence. AB - The phylum Euglenozoa consists of three distinct groups: the euglenoids, diplonemids and kinetoplastids. The phylogenetic position of the diplonemids within this phylum remains unsettled, since both morphological and molecular data produce weak and contradictory results. It is shown here that taxonomic sampling, G+C content bias, mutational saturation and differences of evolutionary rate among lineages are major factors affecting the topology of the small-subunit rRNA euglenozoan tree. When these problems are minimized by using a larger diplonemid sampling (including a sequence of environmental origin) and correcting for G+C bias (by using both paralinear distances or an unbiased dataset), a diplonemids+euglenoids sisterhood is retrieved. Bootstrap support for this relationship is still moderate, but it is retrieved by all analysis methods, overcoming previously reported disagreements. In addition, the inclusion of a large number of euglenoid sequences in the analysis improves some phylogenetic relationships within this group. Some problematic taxa, such as the species Khawkinea quartana, are now placed with high bootstrap support and monophyly is found for two interesting groups (the photosynthetic genera Eutreptia+Eutreptiella and the loricate genera Strombomonas+Trachelomonas), although with weak statistical support. PMID- 11760965 TI - Is characterization of a single isolate sufficient for valid publication of a new genus or species? Proposal to modify recommendation 30b of the Bacteriological Code (1990 Revision). AB - From 1990 to 2000, the number of published named taxa based upon new isolates at species and genus levels in International Journal of Systematic and Evolutionary Microbiology, formerly International Journal of Systematic Bacteriology, have increased by approximately four- and sevenfold, respectively. New taxa based upon characterization of only a single isolate remained at around 40% for both categories. The Bacteriological Code (1990 Revision) has no recommendations on the number of strains required for definition of new taxa. For a few groups, a minimum number of 5-10 strains has been suggested in minimal standards. Since an exponential increase in new taxa can be expected in the future, the authors discuss problems related to naming new species and genera based upon descriptions of a single isolate and suggest that this practice is re-evaluated. It is proposed that the following should be added to Recommendation 30b of the Bacteriological Code: 'Descriptions should be based on as many strains as possible (minimum five), representing different sources with respect to geography and ecology in order to be well characterized both phenotypically and genotypically, to establish the centre (from which the type strain could be chosen) and the extent of the cluster to be named. In addition, comparative studies should be performed, including reference strains that represent neighbouring species and/or genera, in order to give descriptions that are sufficiently detailed to allow differentiation from these neighbours.' PMID- 11760966 TI - Postmarketing drug surveillance: what it would take to make it work. PMID- 11760967 TI - Flu vaccination in Alberta long-term care facilities. PMID- 11760968 TI - Too many serpents spoil the symbol. PMID- 11760970 TI - Don't forget anserine bursitis. PMID- 11760969 TI - Hereditary nonpolyposis colon cancer. PMID- 11760972 TI - Baseline staging tests in primary breast cancer. PMID- 11760971 TI - Longer waits for breast cancer surgery in Quebec could be good news. PMID- 11760973 TI - For expert literature searching, call a librarian. PMID- 11760974 TI - Evaluating the risks of therapies for acute coronary syndromes. PMID- 11760975 TI - Predicting performance on the Royal College of Physicians and Surgeons of Canada internal medicine written examination. AB - BACKGROUND: Although the written component of the Royal College of Physicians and Surgeons of Canada (RCPSC)internal medicine examination is important for obtaining licensure and certification as a specialist, no methods exist to predict a candidate's performance on the examination. METHOD: We obtained data from 5 Canadian universities from 1988 to 1998 in order to compare raw scores from the American Internal Medicine In-Training Examination (AIMI-TE) with raw scores and outcomes (pass or fail) of the written component of the RCPSC internal medicine examination. RESULTS: Mean scores on the AIMI-TE correlated well with scores on the RCPSC internal medicine written examination for all postgraduate years (r = 0.62, r = 0.55 and r = 0.65 for postgraduate years 1, 2 and 3 respectively). Scores above the 50th percentile on the AIMI-TE w/ere predictive of a low failure rate (< 1.5%) on the RCPSC internal medicine written examination, whereas scores at or below the 10th percentile were associated with a high failure rate (about 24%). INTERPRETATION: Candidates who are eligible to take the written component of the RCPSC certification examination in internal medicine can use the AIMI-TE to predict their performance on the Canadian examination. The AIMI-TE is a useful test for residents in all levels of training, because the examination scores have a strong relation to expected performance on the Canadian examination for each year of postgraduate training. PMID- 11760976 TI - Does bed rest after cervical or lumbar puncture prevent headache? A systematic review and meta-analysis. AB - BACKGROUND: Headache after cervical or lumbar puncture has long been attributed to early mobilization; however, there is little evidence for this. We performed a systematic literature review and meta-analysis of randomized controlled trials to assess whether longer bed rest is better than immediate mobilization or short bed rest in preventing headache. METHODS: We searched EMBASE (1988 to March 2001), MEDLINE (1966 to May 2001), Pascal Biomed (1996 to February 2001), Current Contents (1997 to September 1999), PsycINFO (1966 to May 2001), the Cochrane Controlled Trial Register (last search May 15, 2001), textbooks and references of the papers selected. Studies were eligible if patients underwent cervical or lumbar puncture for any reason and were randomly assigned to either a long or a short period of bed rest. Data were abstracted independently by 2 investigators to a predefined form. RESULTS: We found 16 randomized controlled trials involving 1083 patients assigned to immediate mobilization or a short period of bed rest (up to 8 hours) and 1128 patients assigned to a longer period of bed rest (0.5 to 24 hours). Puncture was performed for anesthesia (5 trials), myelography (6 trials) and diagnostic reasons (5 trials). None of the trials showed that longer bed rest was superior to immediate mobilization or short bed rest for preventing headache after puncture. When pooling the results of the trials in the myelography group and the diagnostic group, the relative risks of headache after puncture were 0.93 (95% confidence interval [CI] 0.81-1.08) and 0.97 (95% CI 0.79 1.19) respectively. We did not pool the results from the trials in the anesthesia group because of clinical heterogeneity, but shorter bed rest appeared to be superior. INTERPRETATION: There was no evidence that longer bed rest after cervical or lumbar puncture was better than immediate mobilization or short bed rest in reducing the incidence of headache. PMID- 11760977 TI - Evaluation of an institution-based protocol for postpartum rubella vaccination. PMID- 11760978 TI - The modern scientific physician: 7. Theory of medicine. PMID- 11760979 TI - Evaluation and management of atherogenic dyslipidemia: beyond low-density lipoprotein cholesterol. PMID- 11760980 TI - The death of a volunteer research subject: lessons to be learned. PMID- 11760981 TI - Intention-to-treat principle. PMID- 11760982 TI - Clinical nutrition: a new series. PMID- 11760983 TI - Clinical nutrition: 1. Protein-energy malnutrition in the inpatient. PMID- 11760985 TI - Taliban rulers curtail women's freedom, health care. PMID- 11760986 TI - "You have 3 minutes to get out": MSF camp brings taste of refugee life to Canada. PMID- 11760984 TI - Is obsessive-compulsive disorder an autoimmune disease? AB - OBSESSIVE-COMPULSIVE DISORDER (OCD) IS A COMMON and debilitating neuropsychiatric disorder. Although it is widely believed to have a genetic basis, no specific genetic factors have been conclusively identified as yet, leading researchers to look for environmental risk factors that may interact with an underlying genetic susceptibility in affected individuals. Recently, there has been increasing interest in a possible link between streptococcal infections and the development of OCD and tic disorders in children. It has been suggested that OCD in some susceptible individuals may be caused by an autoimmune response to streptococcal infections, that is, a similar biological mechanism to that associated with Sydenham's chorea. The term "pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections" (PANDAS) has been used to describe a subset of children with abrupt onset or exacerbations of OCD or tics, or both, following streptococcal infections. Affected children have relatively early symptom onset, characteristic comorbid symptoms and subtle neurological dysfunction. Neuroimaging studies reveal increased basal ganglia volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies with basal ganglia tissue. Vulnerability to developing PANDAS probably involves genetic factors, and elevated levels of D8/17 antibodies may represent a marker of susceptibility to PANDAS. Prophylactic antibiotic treatments have thus far not been shown to be helpful in preventing symptom exacerbations. Intravenous immunoglobulin therapy may be an effective treatment in selected individuals. Further understanding of the role of streptococcal infections in childhood-onset OCD will be important in determining alternative and effective strategies for treatment, early identification and prevention of this common and debilitating psychiatric disorder. PMID- 11760987 TI - Hands across the ocean for world's first trans-Atlantic surgery. PMID- 11760988 TI - Are physicians too rude? PMID- 11760989 TI - Ontario, Quebec compare views on medicare. PMID- 11760990 TI - Angiotensin-Il-receptor blockers and nephropathy in patients with type 2 diabetes. PMID- 11760991 TI - Does smallpox still pose a threat? PMID- 11760992 TI - Gas chromatographic technologies for the analysis of essential oils. AB - Essential oil analysis has basically had one technical goal: to achieve the best possible separation performance by using the most effective, available technology of the day. The result achieved from this may then be used to answer the research or industrial analysis questions which necessitated the analysis. This may be for comparative purposes, where one oil is contrasted with other(s) for quality control or investigation of adulteration, to discover new components, or to characterise the chemical classes of compounds present. Clearly, today the analyst turns to chromatography as the provider of separation and then may supplement that with mass spectrometry to aid identification. The power of GC-MS means that advances in both the separation technique, and improvements in mass spectrometry detection - along with improved data handling tools - will immediately be relevant to the essential oil area. This present review outlines the developmental nature of instrumental approaches to essential oil analysis using gas chromatography. Mass spectrometry will be included to the extent that it represents the hyphenation of choice for most analysts when analysing essential oils. Thus single-column and multi-dimensional analysis will be covered, as will sample handling or introduction techniques prior to the analysis step, where these techniques provide some measure of separation. The recent demonstration of comprehensive gas chromatography will be discussed as the potentially most powerful separation method for essential oils. This brief review is not intended to be a comprehensive dissertation on the field of essential oil analysis since that would require sufficient space to occupy a book in its own right. Rather, it will outline selected considerations and developments, to help explain where new technology has been applied to advantage in this field. PMID- 11760993 TI - Analysis of terpene compounds in Cimicifuga foetida L. by reversed-phase high performance liquid chromatography with evaporative light scattering detection. AB - An RP-HPLC method with evaporative light scattering detection (ELSD) was developed for the analysis of terpene compounds in traditional Chinese medicine. Actein, 27-deoxyactein and cimicifugoside in a typical Chinese medicine of Cimicifuga foetida L. were quantitatively analyzed. Comparing ELSD with UV detection under the same eluent conditions, the former showed better sensitivity and a more stable baseline. The ELSD responses versus sample size of three terpenes and those in double logarithmic were investigated. The good calibration curves in double logarithmic coordinator for actein, 27-deoxyactein and cimicifugoside were obtained. Three solutions for the extraction of the terpene compounds were also compared, the results indicated that methanol-water (80:20) is the best among them. The method was applied to quantify actein, 27-deoxyactein and cimicifugoside in Cimicifuga foetida L. from Hunan, China. It was shown that ELSD is an effective detection method for the analysis of the non-volatile terpenes in traditional Chinese medicine. PMID- 11760994 TI - Liquid chromatographic separation of terpenoid pigments in foods and food products. AB - The newest achievements in the use of various liquid chromatographic techniques such as adsorption and reversed-phase thin-layer chromatography and HPLC employed for the separation and quantitative determination of terpenoid-based color substances in foods and food products are reviewed. The techniques applied for the analysis of individual pigments and pigments classes are surveyed and critically evaluated. Future trends in the separation and identification of pigments in foods and food products are delineated. PMID- 11760995 TI - Effects of fluorescent light and vacuum packaging on the rate of decomposition of pigments in paprika (Capsicum annuum) powder determined by reversed-phase high performance liquid chromatography. AB - The effect of storage time, the presence of light and oxygen on the decomposition rate of carotenoid pigments in paprika (Capsicum annuum) powders was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The similarities and dissimilarities of pigment composition of samples under various storage conditions was elucidated by principal component analysis (PCA) and stepwise regression analysis (SRA). Calculations proved that the overall decomposition rate of pigment sections equally depended on the storage time and on the presence of light and oxygen, the effect of storage time being the most decisive factor while the impact of oxygen was the lowest. The selectivity of decomposition also depended on the storage time and on the presence of oxygen the influence of storage time being the most important. RP-HPLC followed by PCA and SRA can be successfully used for the study of the impact of environmental conditions on the decomposition of carotenoid pigments of paprika powders. PMID- 11760996 TI - Monoterpenic and norisoprenoidic glycoconjugates of Vitis vinifera L. cv. Melon B. as precursors of odorants in Muscadet wines. AB - The volatile monoterpenic and norisoprenoidic compounds released by glycosidase enzyme hydrolysis of C18 reversed-phase isolates from the juice of Vitis vinifera L. cv. Melon B. have been qualitatively and quantitatively determined using GC-MS and GC-FID. The components analyzed were broadly similar to those previously reported for other varieties but the level of bound p-menth-1-en-7,8-diol was higher in this cultivar. Then the monoterpenic and norisoprenoidic volatiles released from the same glycosidic extracts under mild acid conditions, mimicking wine aging conditions, have been analyzed using GC-Olfactometry and GC-MS. The most odorous compounds detected were p-cymene, terpinen-4-ol, cis- and trans vitispiranes, 1,6,6-trimethyl-1,2-dihydronaphtalene (TDN), beta-damascenone and riesling acetal. To assess their potential levels in corresponding wines after ageing, most of these odorants were generated by harsh acid hydrolysis from the precursors extracts and quantitatively determined using SPME and GC-MS/MS. For the development and application of this analysis, the odorants not commercialy available were synthesized. The total amounts of norisoprenoidic odorants generated by acid hydrolysis of the glycosidic extracts were shown to be proportional to the total amounts of these precursors. PMID- 11760997 TI - Gas and liquid chromatography of hydrocarbons in edible vegetable oils. AB - Hydrocarbons, an important part of the minor constituents belonging to vegetable oils are reviewed. Their importance, origin, characterization and detection in edible vegetable oils are considered. The determination of some of them as a means of establishing oil quality and genuineness is also highlighted. The official methodologies, as well as the most commonly procedures used for isolation and analysis are reviewed. Furthermore, novel procedures applying new techniques for determining those compounds are also presented. PMID- 11760998 TI - Nonsaponifiable lipid components of the pollen of elder (Sambucus nigra L.). AB - Pollen of the elder (Sambucus nigra L.) was extracted with chloroform-methanol. The extract was separated by column chromatography into the following groups of compounds: hydrocarbons (8.7%). polycyclic aromatic hydrocarbons (0.2%), complex esters (5.2%), triglycerides (18.7%), hydroxy esters (27.9%), free fatty acids and alcohols (16.8%), free sterols (6.8%), and triterpenic alcohols (4.0%). The nonsaponifiable components (hydrocarbons, fatty acids, alcohols, and sterols) were examined in detail using spectroscopic and chromatographic methods (IR spectroscopy, GC, and GC-MS). The identified compounds were characterized by their mass spectra and Kovats retention indices. The double bond positions and their configurations in unsaturated compounds are also reported. PMID- 11760999 TI - Unusually high levels of non-saponifiable lipids in the fishes escolar and rudderfish identification by gas and thin-layer chromatography. AB - Analysis of the non-saponifiable lipids of the fishes Lepidocybium flavobrunneum and Ruvettus pretiosus (escolar), and Centrolophus niger and Tubbia spp. (rudderfish) was performed. The analyses were used to clarify the cause of recent reports of illness (diarrhoea) in Australia from consumption of purported rudderfish. Both escolar and rudderfish contained very high levels of oil (generally between 14 to 25%, as % wet mass) in the fillet and the oil compositions were different to most seafood. Escolar oil contained mainly wax ester (>90% of oil). The oil from five specimens of rudderfish contained mainly diacylglyceryl ether (DAGE, >80% of oil) or hydrocarbon (>80% of oil, predominately squalene). One rudderfish specimen contained mainly polar lipid. Major differences in oil content and composition, including fatty alcohol and glyceryl ether diols (derived from DAGE), were observed between purported individuals of the same species or related species of rudderfish, raising the possibility of geographic or seasonal differences affecting the oil composition. The oil composition of fish fillet samples associated with the health issues were consistent with the profiles for escolar, rather than rudderfish species. These findings, in particular the lipid class and fatty alcohol profiles, were supported by general protein fingerprinting results and were consistent with the samples originating from individuals of the escolar species L. flavobrunneum. The high wax ester content of the escolar group clarifies the reported diarrhoeal effects to consumers. Purgative properties of high wax ester containing fish oils have been reported for escolar and other species. The results highlight the potential for non-saponifiable lipid profiles to be used for identification of fish fillets and oils to at least group level. PMID- 11761000 TI - Combination of chromatographic and spectroscopic methods for the isolation and characterization of polar guaianolides from Achillea asiatica. AB - Four polar guaianolides, 8alpha-angeloxy-2alpha,4alpha, 10beta-trihydroxy 6betaH,7alphaH, 11betaH-1(5)-guaien- 12,6alpha-olide; 8alpha-angeloxy 1beta,2beta:4beta,5beta-diepoxy- 10beta-hydroxy-6betaH,7alphaH,11betaH-12,6alpha guaianolide; 8alpha-angeloxy-4alpha, 10beta-dihydroxy-2-oxo-6betaH, 7alphaH, 11betaH- 1(5)-guaien- 12,6alpha-olide and 8-desacetyl-matricarin, were isolated from Achillea asiatica and characterized by TLC, MS, IR, HPLC and diode array detection. Purified extracts were separated by means of flash chromatography. HPLC separations were achieved using different methanol-water gradients as mobile phase and LiChrospher 100-RP8 5 microm or Zorbax SB-C8 3.5 microm as stationary phases. The chromatographical data are compared to those of the proazulene 8alpha tigloxy-artabsin which shows antiinflammatory effects. By means of these characteristics the identification of the guaianolides with potential antiphlogistic properties is also possible from other sources. PMID- 11761001 TI - Analysis of non-saponifiable lipids by super-/subcritical-fluid chromatography. AB - Because of the particular properties of carbon dioxide or carbon dioxide/modifier mobile phases, super- or subcritical-fluid chromatography (SFC) can be an alternative to more classical chromatographic methods such as gas chromatography (GC) or high-performance liquid chromatography (HPLC) for the separation of unsaponifiable lipids. These fluids can also be helpful in the extraction and/or the concentration steps of sterols, tocopherols or carotenoids from complex samples. Supercritical extraction, off-line prefractionation or semi-preparative supercritical fluid chromatography, carried out before the analysis are described. The effects on separation of analytical parameters such as pressure, nature of and modifier percentage or stationary phase nature are also reported. The performance of capillary, packed or capillary packed columns is discussed, as well as the consequences of their use (choice of stationary phases, type of coupled detector). Numerous examples of fine separations are reported. PMID- 11761002 TI - Supercritical fluid extraction and chromatography for fat-soluble vitamin analysis. AB - Extraction and chromatographic separation of fat-soluble vitamins is a challenging task, due to the sensitivity of these compounds towards light, oxygen, heat and pH. In light of this, supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) are attractive techniques as they function at considerably milder conditions than conventional solvent-based analytical techniques. Moreover, supercritical techniques consume much less amounts of organic solvents than conventional ones. This review gives a brief description of suitable supercritical media as well as basic theory on SFE and SFC processes. Furthermore, guidelines are provided for optimizing the important extraction and separation parameters to facilitate a successful method development. Finally, applications employing SFE and/or SFC for fat-soluble vitamin enrichment and final determination are reviewed. PMID- 11761003 TI - Techniques for gas chromatography of volatile terpenoids from a range of matrices. AB - The commercial importance of the volatile mono- and sesqui-terpenoids has resulted in a wide range of techiques being used for extraction, concentration, chromatography, and characterisation of constituents. The major chromatographic technique is gas chromatography, and tandem techniques of chromatography linked to further chromatography and spectroscopy, allow much increased resolution, and greater ease of characterisation of terpenes. A wide range of extraction techniques are discussed, and suitability for particular matrices and sample sizes outlined. Chromatography operating conditions and stationary phases, and techniques for solute identification are laid out. A number of applications of terpene analysis in many different matrices are discussed. PMID- 11761004 TI - Chemical characterisation of the different types of volatile oil constituents by various solute retention ratios with the use of conventional and novel commercial gas chromatographic stationary phases. AB - Retention ratios of an unknown solute peak from a volatile oil can help to identify its chemical type. Relative retentions on conventional stationary phases can be used to calculate a polar/non-polar ratio which may suggest it is an aromatic solute or a sesquiterpene hydrocarbon. With dipentyl (DA) cyclodextrin phases, gamma-DA/alpha-DA ratios can indicate a bicyclic or monocyclic monoterpenoid. Temperature change on alpha-DA can pick out a non-alcoholic saturated cyclic monoterpenoid, using 150/125 degrees C. Twenty retention ratios are reviewed involving various phases, including other modified cyclodextrins, liquid crystals, "Chirasil-Val" and crown ethers. Applications to six volatile oils are made using a variety of phases. PMID- 11761005 TI - Quantitation of monoterpenoid compounds with potential medicinal use in biological fluids. AB - Alicyclic monoterpenes are not only used as flavoring substances, but many have also been used in herbal products and as home remedies. Their formal use as potential drugs has recently been recognized. Consequently, the previous emphasis of the analytical methods on separation and identification of components has now evolved to the development of highly sensitive and specific quantitation methods capable of measuring the parent compounds and metabolites in biological fluids in order to meet the demand in drug development. This review aims to survey and describe major quantitative methods for some of the monoterpenes that possess medicinal applications. This review also comments on the favorable aspects of some of these assay methods as well as future trends. PMID- 11761006 TI - Chromatographic performance on a C30-bonded stationary phase of monohydroxycarotenoids with variable chain length or degree of desaturation and of lycopene isomers synthesized by various carotene desaturases. AB - Selectivity towards geometric isomers is a superior feature of a C30 polymeric stationary phase. Therefore, lycopene isomers synthesized in Escherichia coli transformants by catalysis of divers carotene desaturases were separated on this stationary phase. Due to their spectral characteristics and by co-chromatography with nuclear magnetic resonance-characterized carotene standards, some of them could be identified. Most of the lycopene isomers were cyclized by lycopene cyclase yielding mainly 9Z, 13Z and all-E beta-carotene. In contrast, 7,9,7',9'Z prolycopene is accumulating since it cannot be converted by this enzyme. Finally several acyclic hydroxycarotenoids with a chain of 30, 40 and 45 carbon atoms differing in the length of the polyene chain from 9 to 13 were separated on the C30 stationary phase. Longer retention times were observed when the length of the molecule increased and also when the conjugated double bond system was extended. Corresponding monocyclic carotenoids were less retained on the C30 stationary phase and derivatives with an epsilon-ionone end group eluted earlier than with a beta-end group. PMID- 11761007 TI - Improved normal-phase and reversed-phase gradient high-performance liquid chromatography procedures for the analysis of retinoids and carotenoids in human serum, plant and animal tissues. AB - Two high-performance liquid chromatography (HPLC) procedures, a rapid normal phase isocratic method for the analysis primarily of retinol and retinoic acid on a 3 mu silica column, and a reversed-phase gradient method for the simultaneous analysis of retinoids and very polar to nonpolar carotenoids on a 3 mu C18 column, are described. The normal-phase isocratic HPLC procedure is rapid (12 min), requires a sample size of 100 microl or less of serum, and is suitable for routine analysis of retinol in any serum, and of retinol and retinoic acid in serum after administration of retinoic acid. The reversed-phase gradient method is suitable for the simultaneous analysis of very polar to nonpolar carotenoids such as epoxy-xanthophylls and xanthophyll esters, along with other carotenoids and retinoids that occur normally in human serum and other plant and animal tissues. A run time of 30-70 min is necessary, depending on the presence or absence of xanthophyll esters in the sample. PMID- 11761008 TI - Analysis of lipophilic antioxidants in human serum and tissues: tocopherols and carotenoids. AB - Tocopherols and carotenoids are naturally occurring lipophilic micronutrients, suggested to play a role in the prevention of several degenerative diseases. Thus, methods for the quantification of these nutrients in human samples have been developed during recent years. Blood and tissue levels of tocopherols and carotenoids are influenced by a variety of parameters related to disease, age, diet and lifestyle. This review summarizes general aspects of chromatographic analysis of tocopherols and carotenoids in human samples and deals with information on the outcome of human studies, in which such measurements were applied. PMID- 11761009 TI - Chromatography of long chain alcohols (polyprenols) from animal and plant sources. AB - This paper provides a comprehensive overview of existing chromatographic methods for the analysis of long chain alcohols (polyprenols) from animal and plant sources. After a brief introductory discussion on the biological aspects of the polyprenols, the review focuses on various techniques for the isolation, purification, chromatographic separation and detection of polyprenols. PMID- 11761010 TI - Biotechnologically manufactured drugs for inflammatory bowel disease. PMID- 11761011 TI - Influence of bacterial lipopolysaccharide on healing of chronic experimental ulcer in rat. AB - BACKGROUND: Lipopolysaccharides (LPS) are major components of the outer membrane of Gram-negative bacteria, which play a central role as potent endotoxins in the pathogenesis of the Gram-negative septicaemia. Although it is well known that large amounts of endotoxin may produce haemorrhagic lesions in the stomach, the effect of LPS on ulcer healing has not been fully clarified. The aim of the present study was to examine the effect of parenteral injection of LPS at different doses on the course of ulcer healing in rats. METHODS: Gastric ulcers were induced in Wistar rats by serosal application of an acetic acid area. After ulcer induction, vehicle (saline) or E. coli-LPS was injected at various doses (0.1, 1 and 5 mg/kg i.p.) for 7 days. The animals were sacrificed on day 8 after ulcer induction and the following parameters were analysed; ulcer area (planimetry), gastric blood flow (GBF) (H2 gas clearance method), gastric secretion, plasma levels of proinflammatory cytokines such as IL-1beta and TNFalpha, mucosal gene expression for cyclooxygenases (COX-1/-2), apoptosis related proteins (Bax, Bcl-2), TNFalpha, IL-1beta and vascular endothelial growth factor (VEGF). RESULTS: Daily parenteral challenge with LPS resulted in a dose dependent delay in ulcer healing with maximum observed at a dose of 5 mg/kg (12.14 +/- 1.2 mm2 versus 5.18 +/- 0.8 mm2 in the control group). The impairment of ulcer healing in LPS-treated rats was associated with a significant decrease in GBF, increased mRNA expression for IL-1beta, TNFalpha, the rise in plasma IL 1beta and TNFalpha levels, an overexpression of COX-2 and VEGF and imbalance in the ratio between pro-apoptotic Bax and antiapoptotic Bcl-2. The daily administration of 50 mg/kg pentoxifylline by itself failed to accelerate the ulcer healing but attenuated the deleterious effects of LPS on this healing. CONCLUSIONS: 1) Bacterial endotoxin impairs ulcer healing through the decrease in gastric mucosal blood flow, increased expression and release of proinflammatory cytokines IL-1beta and TNFalpha, the imbalance between pro- and anti-apoptotic members of Bcl-2 family via downregulation of antiapoptotic bcl-2, and 2) endotoxin leads to upregulation of genes for VEGF and COX-2, which fail to accelerate the ulcer healing. PMID- 11761012 TI - Transfer of clarithromycin to gastric juice is enhanced by omeprazole in Helicobacter pylori-infected individuals. AB - BACKGROUND: The effects of proton-pump inhibitors and Helicobacter pylori infection on the distribution of drugs employed for the eradication of H. pylori are poorly understood. The aim of this study was to investigate the effects of a 7-day oral administration of 20 mg omeprazole on the distribution of clarithromycin in the gastric juice of individuals with H. pylori infection. METHODS: Eighteen H. pylori-infected dyspeptic male volunteers without endoscopic lesions were enrolled in a study with an open, randomized, two-period crossover design and a 21-day washout period between phases. Plasma and gastric juice concentrations of clarithromycin in subjects with and without omeprazole pretreatment were measured by means of liquid chromatography coupled to tandem mass spectrometry. RESULTS: The maximum concentration of clarithromycin (Cmax) and the area under the time-concentration curve from 0 to 2 h (AUC0-2h) were significantly higher in gastric juice than in plasma. Omeprazole treatment further augmented clarithromycin Cmax and AUC0-2h in gastric juice approximately 2-fold (P < 0.05). CONCLUSIONS: Short-term treatment with omeprazole in H. pylori positive volunteers increases the amount of clarithromycin transferred to the gastric juice, confirming a synergism between these drugs. Our results suggest the presence of an active transport mechanism for clarithromycin from plasma to the gastric lumen, which is influenced by omeprazole. PMID- 11761013 TI - Comparison of diagnostic methods for Helicobacter pylori infection in patients with upper gastrointestinal bleeding. AB - BACKGROUND: Accuracy of the most frequently used tests for diagnosing Helicobacter pylori infection in patients with upper gastrointestinal bleeding of peptic origin is determined. METHODS: Seventy-eight patients with endoscopically proven upper gastrointestinal bleeding of peptic origin were included. The presence of H. pylori was considered when observed from the histology or, if negative, when serology and breath test were both positive. Accuracy of the rapid urease test was estimated in accordance with results obtained with other diagnostic methods. RESULTS: Lesions causing gastrointestinal bleeding were 56 duodenal ulcers, 13 gastric ulcers, 7 pyloric channel ulcers, 13 acute lesions of the gastric mucosa and 16 erosive duodenitis. H. pylori infection was present in 68 patients (87.2%). Forty-four patients had received non-steroidal anti inflammatory drugs. The sensitivity/specificity (%) of the diagnostic methods was 48.5/100 for the rapid urease test, 91/77.8 for the breath test, 89.5/80 for serology and 86.3/100 for histology. The prior consumption of proton-pump inhibitors and antibiotics induced false-negative results in the rapid urease test and breath test, with no effect on serology and histology. CONCLUSIONS: The prevalence of H. pylori infection in patients with upper gastrointestinal bleeding from peptic lesions is high. Sensitivity of the rapid urease test for diagnosing H. pylori is low in this setting. Cases with negative rapid urease test need the combination of two or more additional tests if diagnosis is to be achieved. Cases with positive rapid urease test do not need further investigation for diagnosis. PMID- 11761014 TI - Cerebral response to electric stimulation of the colon and abdominal skin in healthy subjects and patients with irritable bowel syndrome. AB - BACKGROUND: Visceral hyperalgesia may play an important part in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the neuronal afferent pathways in healthy volunteers and IBS patients by recording evoked potentials (EPs) elicited by electrical stimulation of the colon and abdominal skin inside and outside the referred pain area. METHODS: Six healthy subjects and nine IBS patients met the inclusion criteria. Morphology and topography of EPs to painful electrical stimuli were estimated in the rectosigmoid junction and on the skin inside/outside the referred pain areas. RESULTS: The EPs to painful stimuli of the gut showed a shorter latency and a smaller amplitude of the first positive peak (P1) in the IBS group. The controls had a mid-latency frontal positive component after 100 ms, whereas no reliable early activation was seen in the IBS patients. In controls, a single late (>150 ms) positive component was seen, whereas the late component was biphasic in the IBS group. The EPs to painful stimuli of the two skin areas differed in IBS patients, but not in controls. CONCLUSION: Differences in the EPs to electrical painful stimulation of the sigmoid colon and skin inside/outside the experimentally evoked referred pain area were seen comparing healthy subjects and IBS patients. The results indicate altered central nervous system responses. PMID- 11761015 TI - Proximal gastric motor and sensory function in slow transit constipation. AB - BACKGROUND: Slow transit constipation may be part of a more generalized gastrointestinal motility disorder. METHODS: Gastric motor and sensory function were evaluated using a barostat in 17 patients with slow transit constipation and in 16 healthy controls. A step-wise isobaric distension procedure was performed, followed by a barostat procedure including a liquid meal. Symptoms were scored using visual analog scales. Plasma levels of gastrointestinal hormones were determined postprandially. RESULTS: Proximal gastric compliance was significantly reduced in the patients. Basal gastric volume did not differ between patients and controls. Postprandial fundus relaxation was significantly reduced in the patients and correlated significantly with daily upper gastrointestinal symptoms. Postprandial secretion of cholecystokinin and gastrin was reduced in the patients. CONCLUSIONS: In patients with slow transit constipation, proximal gastric compliance is reduced and postprandial fundus relaxation is impaired. These findings support the hypothesis that slow transit constipation may be part of a pan-enteric disorder. PMID- 11761016 TI - Lactose malabsorption and intolerance in the elderly. AB - BACKGROUND: Lactase activity declines with age in rats, but it is not clear whether this model is also shared by humans. Few studies have evaluated lactose intolerance and malabsorption in the elderly and no definite conclusions can be drawn. The aim of our study was therefore to verify the impact of age on lactose intolerance and malabsorption. METHODS: Eighty-four healthy subjects took part in the study. Thirty-three were <65 years, 17 were between 65 and 74 years and 34 were >74 years. All the subjects underwent a preliminary evaluation of intestinal gas production capacity and oro-cecal transit time by H2/CH4 breath test after lactulose. After a 3-day period, an H2/CH4 breath test after lactose was performed. The occurrence of intolerance symptoms during the test and in the 24 h after the test was recorded. RESULTS: Breath H2 and CH4 excretion parameters at fasting and after lactulose did not differ between the three groups. Cumulative breath H2 excretion after lactose was higher in subjects >74 years than in subjects <65 years and in subjects aged 65-74 years, while no difference was found between the latter two groups. In subjects >74 years, the prevalence of lactose malabsorption was higher than in the other two groups, while no significant difference was observed between subjects <65 years and subjects aged 65-74 years. Within the malabsorber subjects, the prevalence of lactose intolerance was higher in subjects <65 years than in those aged 65-74 years and in those aged >74 years. No significant difference was found between the latter two groups. No difference was found between the three groups in terms of daily calcium intake and a significant negative correlation between symptom score and daily calcium intake was only found in the group of subjects aged <65 years. CONCLUSIONS: As age increases, the prevalence of lactose malabsorption shows an increase while the prevalence of intolerance symptoms among malabsorbers shows a decrease. Accordingly, daily calcium intake was similar among the adults and elderly studied. PMID- 11761017 TI - Tissue transglutaminase auto-antibodies in cord blood from children to become celiacs. AB - BACKGROUND: Determination of tissue transglutaminase auto-antibodies (tTGAA) has been shown to be a sensitive and specific diagnostic tool for large-scale screening for celiac disease. The purpose of this study was to measure tissue tTGAA in cord blood in infants that later developed celiac disease to evaluate if this assay could serve as a predictive tool for later development of celiac disease. METHODS: IgG tTGAA were analyzed in cord blood through immunoprecipitation from 51 future celiac patients and 102 age-matched controls. Cut-off level was set at 0.040. RESULTS: No difference in tTGAA levels was found between cord blood from infants who later developed celiac disease and controls (P = 0.746). 2/51 future celiac patients (3.9%) had levels above cut-off-value in cord blood, while 3/102 controls were positive (2.9%) (P = 1.000). tTGAA levels were higher in the 1980s and at the beginning of the 1990s than they have been in recent years (P = 0.003). CONCLUSIONS: Determination of tissue tTGAA in cord blood does not predict future celiac disease in children. tTGAA levels vary with time, which should be considered in retrospective studies analyzing tTGAA. PMID- 11761018 TI - Link between Helicobacter pylori infection and iron-deficiency anaemia in patients with coeliac disease. AB - BACKGROUND: Iron-deficiency anaemia is a frequent finding in coeliac disease. Recent investigations have identified Helicobacter pylori infection as a factor responsible for iron deficiency. We investigated the potential relationship between H. pylori and iron-deficiency anaemia in patients with coeliac disease. METHODS: We conducted a prospective observational cohort study on coeliac patients evaluated for iron-deficiency anaemia. An upper gastrointestinal endoscopy was performed and biopsy specimens of duodenal and gastric mucosa were taken for histological examination and assessment of Helicobacter pylori status. RESULTS: The initial database was 386 subjects. Of these, 24 were excluded because of concomitant potential causes of iron deficiency. Of the 362 enrolled patients, H. pylori was detected in 77 (21%) subjects; of these 55 (71%) had iron deficiency anaemia. Among the 285 H. pylori-negative subjects, 81 (28%) showed anaemia (P < 0.001). We did not find significant differences in gastric histological aspects between patients with or without iron deficiency anaemia. CONCLUSIONS: This study shows a significant association between H. pylori infection and iron-deficiency anaemia in patients with coeliac disease. The discovery of iron-deficiency anaemia in coeliac subjects may constitute another indication for the diagnosis and treatment of this worldwide infection. PMID- 11761019 TI - Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease. AB - BACKGROUND: Oxidative stress is believed to play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. Circulating antioxidants may have a role to play in preventing free radical-mediated tissue injury. METHODS: Plasma vitamin A, E and carotenoid concentrations, leukocytic genomic damage and 8-hydroxy-deoxy-guanosine (8-OHdG) concentration were determined in 46 ulcerative colitis (UC) patients, 37 Crohn disease (CD) patients and 386 controls. A 20 ml blood sample was taken from each subject for antioxidant and 8-OHdG measurements. A food frequency questionnaire was administered to a sample of subjects from each group to evaluate daily intake of dietary compounds. RESULTS: Antioxidant concentration was significantly reduced in IBD patients, particularly in those with active disease, with respect to controls (P < 0.0001). 8-OHdG concentrations were significantly increased in IBD patients compared to controls, independent of disease activity (P < 0.05). No correlation was found between antioxidant and 8-OHdG concentrations. Carotenoid concentrations were significantly reduced in malnourished IBD patients (0.89 +/- 0.14 micromol/l) compared to patients with normal or high body mass index (1.83 +/- 0.12 micromol/l; P < 0.05), independent of disease activity or extension. Protein, fruit and vegetable intakes of IBD patients were significantly lower than those of controls. CONCLUSIONS: Depletion of antioxidants is likely to be important in the pathophysiology of IBD: UC and CD patients show increased free radical peripheral leukocyte DNA damage and decreased plasma antioxidant defenses. These results indicate the necessity of further studies to establish whether optimal vitamin status may improve the clinical course of UC and CD. PMID- 11761020 TI - Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor? AB - BACKGROUND: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. METHODS: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC). 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. RESULTS: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years: P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. CONCLUSIONS: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect. PMID- 11761021 TI - Activated platelets in ulcerative colitis enhance the production of reactive oxygen species by polymorphonuclear leukocytes. AB - BACKGROUND: Although the number of activated platelets increases in the peripheral blood of patients with inflammatory bowel disease (IBD), the role of activated platelets in the polymorphonuclear leukocytes (PMN)-mediated mucosal injury in IBD remains unclear. In the present study, we used luminol-enhanced chemiluminescence (LCL) to examine the influence of platelets from patients with ulcerative colitis (UC) on the production of reactive oxygen species (ROS) by circulating PMN. METHODS: The proportion of P-selectin-positive activated platelets was determined using flow cytometry. PMN from patients with UC and normal controls were stimulated using phorbol 12-myristate 13-acetate with or without autologous platelets, anti-P-selectin monoclonal antibody and thrombin. Indicator PMN from a normal volunteer were stimulated using heterologous platelets from UC patients and normal controls, and LCL signals were registered every 60 sec for 240 min. RESULTS: The proportion of activated platelets was significantly increased in IBD patients. The level of ROS production by PMN did not significantly differ between UC patients and normal controls in the absence of a platelet-PMN interaction. Platelets from UC patients enhanced the amount of ROS produced by indicator PMN significantly more than those from normal controls. This effect was partly diminished by anti-P-selectin monoclonal antibody. CONCLUSIONS: Platelet activation in UC might be responsible for the secondary activation of PMN, which could account for the increase in PMN-mediated tissue injury associated with UC. PMID- 11761023 TI - Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease. AB - BACKGROUND: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). METHODS: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. RESULTS: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered. CONCLUSIONS: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling. PMID- 11761022 TI - Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients. AB - BACKGROUND: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. METHODS: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an antero-posterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. RESULTS: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women (P = 0.03), of ocular and liver involvement (P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs (P = 0.02) was observed. CONCLUSION: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria. PMID- 11761024 TI - Comparison of flow cytometry and histology with mutational screening for p53 and Ki-ras mutations in surveillance of patients with long-standing ulcerative colitis. AB - BACKGROUND: We evaluate the usefulness of screening for p53 and Ki-ras mutations in comparison with histological and flow cytometric findings. METHODS: We analyzed 1486 biopsy samples from 769 locations of 83 patients with long-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 biopsy samples of 16 patients with irritable bowel disease. RESULTS: With respect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/83) of patients, dysplasia in 22.9% (15/83), p53 in 21.7% (18/83) and Ki-ras mutations in 18.1% (15/83) of patients. None of these markers was found in our control group. In 7 out of 10 patients who displayed dysplastic findings during endoscopic surveillance p53 and / or Ki-ras mutations were present in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy (P < 0.001), between dysplasia and p53 mutations (P = 0.05) and between dysplasia and p53 and/or Ki-ras mutations (P = 0.002). No significant associations were found between dysplasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. CONCLUSIONS: These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with long-standing ulcerative colitis. PMID- 11761025 TI - Identification of two potential suppressor gene regions on chromosome arm 14q that are commonly lost in advanced colorectal carcinomas. AB - BACKGROUND: Remarkably little is known about the molecular alterations contributing to the establishment of a distant metastasis from a primary colorectal carcinoma. Previous studies on primary colorectal carcinomas have suggested an association between loss of chromosome 14 sequences and cancer progression. METHODS: In the present study, we analyzed 20 distant metastases and peripheral blood samples from 18 patients using 24 microsatellite markers spanning chromosome arm 14q. In addition, DNA from microdissected corresponding primary tumors (formalin-fixed and paraffin-embedded) was analyzed at selected 14q loci. RESULTS: Sixty-five percent (13/20) of the metastases, from 11/18 patients, showed loss of one or more markers at 14q, and the majority (94%) of the primary carcinomas showed identical 14q genotypes to those found in the metastasis. Two minimal common deleted regions were delineated in the metastases, one between markers D14S288-D14S52 at 14q13-21 and the other between D14S284 D14S81 at 14q24-31, pinpointing two previously unrecognized map positions for potential target genes. The genotype pattern of five tumors was consistent with monosomy or large chromosomal deletions spanning both potential suppressor regions. The reasons for monosomy in cancer remain unknown, but our data support the hypothesis that deletions of several tumor suppressor genes are more readily obtained by one chromosome loss than by several molecular events, and through this unison loss a growth advantage may be provided. CONCLUSION: Our data suggest that 14q loss is not a rate-limiting event in colorectal metastasis formation, but the high frequency of this alteration in primary tumors with metastatic ability, as well as in the metastases themselves, suggests it is part of the tumor clone with selective growth capacity. PMID- 11761026 TI - Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study. AB - BACKGROUND: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding. PMID- 11761027 TI - Selective involvement of calcium and calcium channels in stimulated mucin secretion from rat colon. AB - BACKGROUND: The cellular mechanisms involved in the mucin secretion of rat colon are unknown. The objective of the present study was thus to determine the role of extracellular calcium and of L-type calcium channels in rat intestinal mucin discharge. METHODS: The experiments were conducted using the isolated vascularly perfused rat colon. Mucin secretion was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Intra-arterial bethanechol (200 microM) or luminal deoxycholate (5 mM) produced a significant mucin discharge (609% and 386% of controls, respectively). The colonic mucin output induced by these two secretagogues was significantly inhibited by arterial administration of EGTA (2 mM), verapamil (100 microM) or nifedipine (50 microM). In contrast, luminal EGTA (2 mM) had no inhibitory effect. Intra-arterial infusion of the calmodulin antagonist trifluoperazine (10 microM) also reduced mucin discharge induced by bethanechol or deoxycholate (304% and 223% of controls, respectively). Colonic mucin secretion was significantly stimulated after intra-arterial infusion of 3 isobutyl-methylxanthine (IBMX, 100 microM) or forskolin (2-20 microM). Stimulation by forskolin was unaffected by arterial EGTA, verapamil, nifedipine or trifluoperazine. CONCLUSION: In the isolated vascularly perfused rat colon, mucin discharge induced by bethanechol or deoxycholate requires extracellular calcium and the activation of voltage-dependent calcium channels of L-type. In contrast, forskolin does not appear to stimulate mucin release by increasing calcium entry. PMID- 11761028 TI - Time course profile and cell-type-specific production of monokine induced by interferon-gamma in Concanavalin A-induced hepatic injury in mice: comparative study with interferon-inducible protein-10. AB - BACKGROUND: We have previously shown that interferon-inducible protein-10 (IP 10), a chemokine for activated lymphocytes, was specifically induced in the liver of Concanavalin A (Con A)-treated mice. The aim of this study was to investigate the time course profile and cell-type-specific hepatic production of monokine induced by interferon-gamma (MIG), a chemokine which shares its receptor and most of its activity with IP-10, in Con A-treated mice and to compare them with those of IP-10. METHODS: Hepatic mRNA expression of MIG and IP-10 was studied by means of Northern blot analysis and in situ hybridization in Con A-treated mice. The levels of MIG and IP-10 in the serum and culture supernatants of murine hepatoma , hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage derived cell lines were determined by means of specific enzyme-linked immunosorbent assays. RESULTS: The serum level of MIG slowly reached a maximum at 12 h after Con A injection and remained elevated for a long time, whereas that of IP-10 reached a maximum at 3 h and declined quickly, a finding supported by Northern blot analysis. Using in situ hybridization, the mRNA of MIG as well as IP-10 was found to be expressed in hepatocytes and hepatic non-parenchymal cells. Similar to IP-10, MIG was produced by hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines in vitro. CONCLUSIONS: Although both MIG and IP-10 were produced by hepatocytes and hepatic non-parenchymal cells in Con A-treated mice, the time course profile of MIG was distinguishable from that of IP-10. The fact that hepatic MIG and IP-10 were produced sequentially in this hepatitis model may suggest that a non-redundant role is played by these two chemokines in the process of hepatic necro inflammation. PMID- 11761029 TI - Factors associated with tolerance to, and discomfort with, unsedated diagnostic gastroscopy. AB - BACKGROUND: Identification of patients likely to experience high levels of discomfort during unsedated gastroscopy would be useful as these patients could be prospectively targeted for sedation. We prospectively assessed patient and endoscopic variables in subjects attending for endoscopy in order to identify factors associated with patients' experience of the unsedated examination. METHODS: We studied 508 patients attending for routine diagnostic gastroscopy. Clinical and endoscopic data were collected and patients completed a two-part questionnaire assessing their anxiety with, and experience of, the procedure. RESULTS: Thirty-nine subjects failed to complete the initial unsedated endoscopy. Failure to tolerate endoscopy was associated with younger age (P = 0.002) and examination with a standard-bore (> or = 9.0 mm) endoscope (P = 0.004). High levels of patient discomfort during the procedure were associated with younger age (P < 0.001), high levels of pre-endoscopic anxiety (P < 0.001), high levels of pre-endoscopic discomfort due to throat spray (P = 0.02) and examination with a standard-bore endoscope (P < 0.001). Preference for sedation during future examinations was related to female gender (P = 0.02), young age (P = 0.02), high levels of apprehension (P < 0.001), the examining doctor (P = 0.002) and use of a standard-bore endoscope (P < 0.001). CONCLUSIONS: Discrete clinical characteristics and endoscopic variables are associated with patients' experience of unsedated endoscopy. Further work might result in an algorithm for identifying patients who would benefit from sedation prior to gastroscopy. PMID- 11761030 TI - Eosinophilic gastroenteritis: our recent experience: one-year experience of atypical onset of an uncommon disease. AB - Eosinophilic gastroenteritis is an unusual entity that is rarely found in daily clinical practise. Its aetiology is unknown and diagnosis can be made microscopically with evidence of massive eosinophilic infiltration in patients with chronic gastrointestinal symptoms, excluding entities that may cause such findings (parasitic infestation, medical therapy, inflammatory bowel disease, and so on). Allergic processes are usually associated and these normally respond well to steroids. We present our last year's experience of four women with eosinophilic gastroenteritis with an extraordinary atypical clinical onset. Two of the women presented with an acute abdomen and two with isolated colonic involvement. The management of acute abdomen avoiding surgery and a complete response with azathioprine are the outstanding variables that make our recent cases of special interest. Demographic variables were similar to others reported from our medium, with the exception of a higher incidence of women. Our cases suggest the wide spectrum of clinical presentations and show the high suspicion index needed for a diagnosis that is made by pathologists. PMID- 11761031 TI - Effects of worry and evaluation stress on interhemispheric interaction. AB - Theories of cognitive functioning in anxiety propose decreased processing efficiency associated with worry but have paid scant attention to possible neural mechanisms. This study examined interhemispheric processing in individuals differing in self-reported worry under high- and low-evaluative conditions. Measures of interhemispheric processing were letter-matching tasks, with matches occurring either within or across hemispheres and requiring either a physical identity (A-A) or a name identity match (A-a). Results indicated that the across hemisphere advantage (AHA) for the more difficult name identity task was exaggerated under high-evaluative conditions, indicating that interhemispheric processing was especially beneficial under the processing load of evaluation stress. Regardless of task condition, high worriers displayed a reduced AHA compared with low worriers, reflecting ineffective coordination of interhemispheric resources in worriers. PMID- 11761032 TI - Object naming and semantic knowledge in temporal lobe epilepsy. AB - Object-naming impairment is common among temporal lobe epilepsy (TLE) patients, but other aspects of semantic memory have received limited attention in this population. This study examined object-naming ability and depth of semantic knowledge in healthy controls (n = 29) and patients with early onset TLE (n = 21). After administration of the Boston Naming Test (BNT), the authors asked participants to provide detailed definitions of 6 BNT objects. The TLE group demonstrated a significant deficit relative to controls in both object-naming ability and semantic knowledge for the target objects, even after controlling for IQ. In a multiple regression analysis that included other neuropsychological test scores as independent variables, the semantic knowledge score was the only significant predictor of patients' object-naming performance. Thus, at the group level, early onset TLE patients have a semantic knowledge deficit that contributes to dysnomia. PMID- 11761033 TI - The relationship between recall and recognition in amnesia: effects of matching recognition between patients with amnesia and controls. AB - To examine the relationship between recall and recognition memory in amnesia, the authors conducted 2 experiments in which recognition memory was equated between patients with amnesia and control participants. It was then determined whether recall was also similar across groups. In Experiment 1, recognition was equated by providing amnesic patients with additional study exposures; in Experiment 2, recognition was equated by testing controls following a longer delay. These different methods of equating recognition across groups led to divergent results because amnesic patients' recall performance was lower than controls' recall performance in Experiment 1 but not in Experiment 2. These findings are accounted for by considering the differential contribution of recollection and familiarity to the performance of amnesic patients and controls in the 2 experiments. PMID- 11761034 TI - Selective attentional processing and the right hemisphere: effects of aging and alcoholism. AB - Thirty-seven nonalcoholic individuals (22 women, 15 men), ages 26-76, and 36 abstinent alcoholic individuals (11 women, 25 men), ages 31-74, participated in a cued-detection task that assessed right hemisphere (RH) functioning associated with aging and alcoholism. Young controls were less reliant on cues following RH activation, which is consistent with the view that the RH has an advantage because it has the ability to attend to a broader spatial array than does the left hemisphere (LH). This RH advantage was not obtained in older controls or alcoholic participants. The pattern of results for the older nonalcoholic participants indicated that they neither benefited from valid cues following LH activation nor exhibited enhanced processing on invalid cue trials following RH activation. The results for the alcoholic participants were consistent with RH functional decline, but did not support the view that alcoholism and aging have synergistic effects. PMID- 11761035 TI - Interpreting Stroop interference: an analysis of differences between task versions. AB - The present study investigated methodological differences between the clinical version of the Stroop Color and Word Test and the computerized single-trial version. Three experiments show that different presentations of the Stroop task can produce different levels of interference. The 1st experiment examined the effect of blocking; the 2nd experiment examined different control conditions. Greater interference in the blocked clinical version appears to result from lower response times (RTs) in the neutral condition, not from greater RTs in the incongruent condition. Experiment 3 examined the impact of shifting attention across locations while responding to Stroop stimuli. The present set of findings sheds light on the inconsistency in the clinical literature and demonstrates that the method and selection of neutral stimuli (that provide the baseline by which interference is measured) are critical because they clearly can change performance. PMID- 11761036 TI - Midlife aging, open-ended planning, and laboratory measures of executive function. AB - The frontal lobes show early signs of structural and functional change in the course of adult aging. The 1st study of the current article examined whether midlife aging influences open-ended planning, a skill that is particularly sensitive to frontal lobe damage. There were no midlife declines in the ability to carry out variants of the T. Shallice and P. Burgess (1991) Six Elements and Multiple Errands Tests. Younger adults were more likely to break individual task rules. In a 2nd experiment, middle-aged adults performed worse than young adults did on laboratory executive tests sensitive to frontal lobe damage-Self-Ordered Pointing and the Wisconsin Card Sorting Test (N. M. Fristoe, T. A. Salthouse, & J. L. Woodard, 1997). In spite of changes in novel executive test performance, real-world executive skills appear to be spared in midlife aging. PMID- 11761037 TI - Conceptual implicit memory performance in Alzheimer's disease. AB - Alzheimer's disease (AD) patients often exhibit deficits on conceptual implicit memory tests such as category exemplar generation and word association. However, these tests rely on word production abilities, which are known to be disrupted by AD. The current study assessed conceptual implicit memory performance in AD patients and elderly control participants using a conceptual priming task that did not require word production (i.e., semantic decision). Memory performance was also examined using a category exemplar generation test (i.e., a conceptual priming task that required word production) and a recognition memory test. AD patients exhibited deficits on the semantic decision task, the category exemplar generation task, and the recognition memory task. The results indicate that the conceptual memory deficits observed in AD patients cannot be attributed completely to word production difficulties. PMID- 11761038 TI - Neuropsychological differences among empirically derived clinical subtypes of schizophrenia. AB - Neuropsychological profile differences between empirically derived clinical subtypes of schizophrenia were examined. Two hundred five patients and 209 demographically matched controls were administered a neuropsychological battery examining 8 domains. Subtypes included negative, disorganized, paranoid, Schneiderian, and mild. All subtypes displayed a neuropsychological profile of generalized impairment with greater deficits in learning, memory, and attention. Results were suggestive of diffuse cognitive dysfunction in schizophrenia with more severe deficits in learning and memory relative to executive skills. This pattern of greater learning and memory impairment was pronounced for disorganized patients. In contrast, paranoid patients outperformed disorganized and negative patients in several domains. These findings reflect bilateral frontal-temporal dysfunction, particularly in disorganized and negative patients. Subtype differences highlight the importance of conceptualizing schizophrenia as a multifocal disorder. PMID- 11761039 TI - Controlled and automatic processing during animal word list generation in schizophrenia. AB - Controlled and automatic aspects of semantic-associative functioning in schizophrenia were investigated by evaluating performance on animal word list generation (WLG). Responses from control (n = 47) and patient (n = 38) participants were subjected to multidimensional scaling (MDS), cluster analysis (CA), and indices on the basis of number of shared attributes (SA) between consecutive responses. Patient MDS results accounted for less variance and contained more error than control data. CA results yielded fewer and less clear animal-response subgroups among patients yet demonstrated intact associations among strongly related exemplars. The SA indices revealed better clustering and more effective switching among response clusters in controls than patients. Results suggest that animal WLG in schizophrenia is compromised both by aberrant automatic semantic-associative network activation and by controlled processes such as search, access, and selection. This pattern is consistent with prominent frontotemporal pathology evident in the disorder. PMID- 11761040 TI - Evidence for the pathological right-handedness hypothesis. AB - The present study investigated handedness of 109 Korean patients with temporal lobe epilepsy (TLE) and 120 normal control participants. Left TLE was associated with a significantly raised incidence of left-handers relative to normal controls. More important for the present purpose, right TLE was associated with a significantly raised incidence of strong right-handers relative to normal controls. This finding indicates that certain early damage to the right brain causes a mild hypofunction of the left hand in natural weak right-handers, which in turn causes the patient to switch to strong right-handedness. To the authors' knowledge, this finding provides the 1st empirical evidence supporting the pathological right-handedness hypothesis. Prior failure to find evidence of pathological right-handedness may reflect the low base rate of natural left handers rather than true absence of pathological right-handers. PMID- 11761041 TI - Hemispheric perception of emotional valence from facial expressions. AB - The authors previously reported that normal subjects are better at discriminating happy from neutral faces when the happy face is located to the viewer's right of the neutral face; conversely, discrimination of sad from neutral faces is better when the sad face is shown to the left, supporting a role for the left hemisphere in processing positive valence and for the right hemisphere in processing negative valence. Here, the authors extend this same task to subjects with unilateral cerebral damage (31 right, 28 left). Subjects with right damage performed worse when discriminating sad faces shown on the left, consistent with the prior findings. However, subjects with either left or right damage actually performed superior to normal controls when discriminating happy faces shown on the left. The authors suggest that perception of negative valence relies preferentially on the right hemisphere, whereas perception of positive valence relies on both left and right hemispheres. PMID- 11761042 TI - Face learning and memory: the twins test. AB - The clinical utility of current face recognition tests has been questioned. To evaluate if a new paradigm may measure this type of memory more accurately, the authors created a novel test to examine face learning (previously uninvestigated) and short- and long-term retention. For this initial investigation of test sensitivity to hemisphere of dysfunction, patients with surgical resection from a temporal lobe and healthy subjects were tested. Recognition was evaluated on 3 trials: after a single exposure, after 4 exposures (for learning), and after a 24 hr delay interval. Patients with a right resection performed significantly worse than healthy controls and patients with left resection. There was no difference between patients with a left resection and controls. Classification of individual patients to side of resection based on test results showed higher sensitivity (82%) than published for other tests and maintained good specificity (79%). PMID- 11761043 TI - Modal attention asymmetry in patients with schizophrenia and bipolar disorder. AB - This cross-sectional study examined modal attention asymmetries in patients with schizophrenia (n = 47) and bipolar disorder (n = 42), as contrasted to a matched sample comparison group of normal participants (n = 89). A test of continuous auditory and visual attention was the primary measure. The data were analyzed from 2 experimental conditions: simple modal responses (auditory and visual) and modal switching responses (ipsimodal and cross-modal switching). In the simple modal condition, patients with schizophrenia demonstrated a visual over auditory asymmetry; patients with bipolar disorder showed no differences. In modal switching conditions, however, patients with bipolar disorder displayed a significant auditory over visual asymmetry. No main effect was detected between medications and attention functioning. Results are discussed in light of differentiating these 2 populations on the basis of modal specificity of attention functioning. PMID- 11761044 TI - Learning disabilities and executive dysfunction in boys with attention deficit/hyperactivity disorder. AB - The effect of comorbid reading or arithmetic learning disabilities (LDs) on neuropsychological function in attention-deficit/hyperactivity disorder (ADHD) was studied. Participants were young males diagnosed with ADHD, with and without LD, and non-ADHD, non-LD male controls of similar age. LD was defined by combined regression-based and low-achievement classifications. Analyses adjusted for the effect of psychiatric comorbidity, age, and socioeconomic status on neuropsychological function. Children who had both ADHD and LD were significantly more impaired on both executive and nonexecutive functions than ADHD children without LD. Neuropsychological performance was most impaired in ADHD with combined arithmetic and reading disability. These data indicate that comorbid LD, especially arithmetic disability, significantly increases the severity of executive function impairment in ADHD. PMID- 11761045 TI - Porteus Maze performance following traumatic brain injury in children. AB - To investigate planning in traumatically brain injured children, the authors gave the Porteus Maze Test (PMT; S. D. Porteus, 1959) to 276 pediatric patients who had sustained a traumatic brain injury (TBI) at least 3 years previously. Sensitivity of the PMT to TBI severity, age at test, and volume of focal brain lesions detected by magnetic resonance imaging was also studied. The Peabody Picture Vocabulary Test-Revised (L. M. Dunn & L. M. Dunn, 1981) was also administered as a control measure. Results indicated that the PMT was highly sensitive to TBI severity and to volume of circumscribed prefrontal lesions. In contrast to the PMT data, receptive vocabulary was related to injury severity but not to discrete prefrontal lesions. Implications for mechanisms of cognitive deficit after TBI in children are discussed. PMID- 11761046 TI - Neural activation during frequency-memory performance. AB - Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory. PMID- 11761047 TI - Automatic hypermnesia and impaired recollection in schizophrenia. AB - Evidence from studies of nonmnemonic automatic cognitive processes provides reason to expect that schizophrenia is associated with exaggerated automatic memory (implicit memory), or automatic hypermnesia. Participants with schizophrenia (n = 22) and control participants (n = 26) were compared on word stem completion (WSC) and list discrimination (LD) tasks administered using the process dissociation procedure. Unadjusted, extended measurement model and dual process signal-detection methods were used to estimate recollection and automatic memory indices. Schizophrenia was associated with automatic hypermnesia on the WSC task and impaired recollection on both tasks. Thought disorder was associated with even greater automatic hypermnesia. The absence of automatic hypermnesia on the LD task was interpreted with reference to the neuropsychological bases of context and content memory. PMID- 11761048 TI - Names and words without meaning: incidental postmorbid semantic learning in a person with extensive bilateral medial temporal damage. AB - The authors describe a densely amnesic man who has acquired explicit semantic knowledge of famous names and vocabulary words that entered popular culture after the onset of his amnesia. This new semantic knowledge was temporally graded and existed over and above the implicit memory he demonstrated in reading speed and accuracy, familiarity ratings, and his ability to make correct guesses on unfamiliar items. However, his postmorbid knowledge was limited to verbal labels denoting famous people and words; he possessed virtually no explicit knowledge of the meaning of these words or the identities of these individuals, although there was some evidence that some of this information had been acquired at an implicit level. Findings are discussed in the context of a neural network model (J. L. McClelland, B. L. McNaughton, & R. C. O'Reilly, 1995) of semantic acquisition. PMID- 11761049 TI - Left and right hemisphere contributions to physiognomic and verbal discrimination. AB - The relative contributions of the right- and left-temporal lobes in rapid recognition of faces and letters were studied in patients with anterior right- or left-temporal lobe excisions and a matched control group. On the basis of findings in patients with unilateral and bilateral brain damage, it was hypothesized that left hemisphere damage would not change the reaction time of letters analyzed by the right hemisphere and that right hemisphere damage would not change the reaction time of faces analyzed by the left hemisphere. The hypothesis was supported for letters but not for faces. Patients in the right temporal group, particularly those with large hippocampal removals, were slow to recognize faces in both visual fields. Two possible explanations for the findings with faces are explored: One holds that right hemisphere mechanisms are involved even when a face is presented to the left hemisphere for rapid recognition; the other holds that specialized encoding is carried out by the right hemisphere during learning, with the encoded template then being used by each hemisphere independently. PMID- 11761050 TI - Superior episodic memory is associated with interhemispheric processing. AB - The dependence of episodic memories on interhemispheric processing was tested. In Experiment 1, positive familial sinistrality (FS+; e.g., presence of left-handed relatives) was associated with superior episodic memory and inferior implicit memory in comparison with negative familial sinistrality (i.e., FS-). This reflected a greater degree of interhemispheric interaction in FS+ participants, which was hypothesized as facilitating episodic memory. In Experiment 2, the authors directly manipulated inter- versus intrahemispheric processing using tests of episodic (recognition) and semantic (lexical decision) memory in which letter strings were presented twice within trial blocks. Semantic memory was superior when the 2nd presentation went to the same hemisphere as the 1st. Episodic memory, however, was superior when the 2nd presentation of a stimulus went to the opposite hemisphere. Results support an interhemispheric processing basis for episodic memories. PMID- 11761051 TI - Improved detection of differential information-processing speed deficits between two disease-course types of multiple sclerosis. AB - Patients with multiple sclerosis (MS) frequently demonstrate impairments of information-processing speed (IPS) on measures such as the Paced Auditory Serial Addition Test (PASAT; D. M. A. Gronwall, 1977). The authors have previously shown that their new PASAT scoring method (mean dyad score) is better correlated in comparison with more traditional PASAT scoring method(s), with magnetic resonance imaging measurement of the total area (mm2) of white-matter sclerotic lesions (P. J. Snyder & J. C. Cappelleri, 2001). The present study reports that the mean dyad score discriminated 20 relapsing-remitting MS (RRMS) patients from 15 secondary progressive MS (SPMS) patients noticeably better than did the standard scoring method(s). Mean dyad scores < 4.13 classified patients as having SPMS with 73% accuracy (sensitivity), whereas scores > or = 4.13 classified patients as having RRMS with 80% accuracy (specificity). PMID- 11761052 TI - Building episodic connections: changes in episodic priming with age and dementia. AB - Previous studies of associative encoding that used explicit retrieval tasks have shown both age- and dementia of the Alzheimer type (DAT)-related declines, but such results may be biased by group differences in explicit retrieval. In the present experiment, the authors assessed implicit associative encoding for 25 younger adults (ages 18-25), 73 healthy older adults (ages 59-91), and 65 adults with DAT (ages 59-91) during a speeded word-naming task using an episodic priming measure. Episodic priming refers to the facilitation in responding to a target word after repetition of both words in a prime-target pair, in comparison with simple repetition of the target word with a new prime on each presentation. In contrast with other studies of implicit associative encoding that did not use an implicit episodic priming measure, the present study found both age- and DAT related declines in associative encoding under conditions of massed learning trials. PMID- 11761053 TI - Beyond reinforcement: the evolution of premating isolation by direct selection on preferences and postmating, prezygotic incompatibilities. AB - The evolution of premating isolation after secondary contact is primarily considered in the guise of reinforcement, which relies on low hybrid fitness as the driving force for mating preference divergence. Here I consider two additional forces that may play a substantial role in the adaptive evolution of premating isolation, direct selection on preferences and indirect selection against postmating, prezygotic incompatibilities. First, I argue that a combination of ecological character displacement and sensory bias can cause direct selection on preferences that results in the pattern of reproductive character displacement. Both analytical and numerical methods are then used to demonstrate that, as expected from work in single populations, such direct selection will easily overwhelm indirect selection due to low hybrid fitness as the primary determinant of preference evolution. Second, postmating, prezygotic incompatibilities are presented as a driving force in the evolution of premating isolation. Two classes of these mechanisms, those increasing female mortality after mating but before producing offspring and those reducing female fertility, are shown to be identical in their effects on preference divergence. Analytical and numerical techniques are then used to demonstrate that postmating, prezygotic factors may place strong selection on preference divergence. These selective forces are shown to be comparable if not greater than those produced by the low fitness of hybrids. PMID- 11761054 TI - Selection for recombination in small populations. AB - The reasons that sex and recombination are so widespread remain elusive. One popular hypothesis is that sex and recombination promote adaptation to a changing environment. The strongest evidence that increased recombination may evolve because recombination promotes adaptation comes from artificially selected populations. Recombination rates have been found to increase as a correlated response to selection on traits unrelated to recombination in several artificial selection experiments and in a comparison of domesticated and nondomesticated mammals. There are, however, several alternative explanations for the increase in recombination in such populations, including two different evolutionary explanations. The first is that the form of selection is epistatic, generating linkage disequilibria among selected loci, which can indirectly favor modifier alleles that increase recombination. The second is that random genetic drift in selected populations tends to generate disequilibria such that beneficial alleles are often found in different individuals; modifier alleles that increase recombination can bring together such favorable alleles and thus may be found in individuals with greater fitness. In this paper, we compare the evolutionary forces acting on recombination in finite populations subject to strong selection. To our surprise, we found that drift accounted for the majority of selection for increased recombination observed in simulations of small to moderately large populations, suggesting that, unless selected populations are large, epistasis plays a secondary role in the evolution of recombination. PMID- 11761055 TI - Evidence for Dobzhansky-Muller incompatibilites contributing to the sterility of hybrids between Mimulus guttatus and M. nasutus. AB - Both chromosomal rearrangements and negative interactions among loci (Dobzhansky Muller incompatibilities) have been advanced as the genetic mechanism underlying the sterility of interspecific hybrids. These alternatives invoke very different evolutionary histories during speciation and also predict different patterns of sterility in artificial hybrids. Chromosomal rearrangements require drift, inbreeding, or other special conditions for initial fixation and, because heterozygosity per se generates any problems with gamete formation, F1 hybrids will be most infertile. In contrast, Dobzhansky-Muller incompatibilities may arise as byproducts of adaptive evolution and often affect the segregating F2 generation most severely. To distinguish the effects of these two mechanisms early in divergence, we investigated the quantitative genetics of hybrid sterility in a line cross between two members of the Mimulus guttatus species complex (M. guttatus and M. nasutus). Hybrids showed partial male and female sterility, and the patterns of infertility were not consistent with the action of chromosomal rearrangements alone. F2 and F1 hybrids exhibited equal decreases in pollen viability (> 40%) relative to the highly fertile parental lines. A large excess of completely pollen-sterile F2 genotypes also pointed to the segregation of Dobzhansky-Muller incompatibility factors affecting male fertility. Female fertility showed a pattern similarly consistent with epistatic interactions: F2 hybrids produced far fewer seeds per flower than F1 hybrids (88.0 +/- 2.8 vs. 162.9 +/- 8.5 SE, respectively) and either parental line, and many F2 genotypes were completely female sterile. Dobzhansky-Muller interactions also resulted in the breakdown of several nonreproductive characters and appear to contribute to correlations between male and female fertility in the F2 generation. These results parallel and contrast with the genetics of postzygotic isolation in model animal systems and are a first step toward understanding the process of speciation in this well-studied group of flowering plants. PMID- 11761056 TI - Molecular phylogeography, reticulation, and lineage sorting in Mediterranean Senecio sect. Senecio (Asteraceae). AB - The Mediterranean species complex of Senecio serves to illustrate evolutionary processes that are likely to confound phylogenetic inference, including rapid diversification, gene tree-species tree discordance, reticulation, interlocus concerted evolution, and lack of complete lineage sorting. Phylogeographic patterns of chloroplast DNA (cpDNA) haplotype variation were studied by sampling 156 populations (502 individuals) across 18 species of the complex, and a species phylogeny was reconstructed based on sequences from the internal transcribed spacer (ITS) regions of nuclear ribosomal DNA. For a subset of species, randomly amplified polymorphic DNAs (RAPDs) provided reference points for comparison with the cpDNA and ITS datasets. Two classes of cpDNA haplotypes were identified, with each predominating in certain parts of the Mediterranean region. However, with the exception of S. gallicus, intraspecific phylogeographic structure is limited, and only a few haplotypes detected were species-specific. Nuclear sequence divergence is low, and several unresolved phylogenetic groupings are suggestive of near simultaneous diversification. Two well-supported ITS clades contain the majority of species, amongst which there is a pronounced sharing of cpDNA haplotypes. Our data are not capable of diagnosing the relative impact of reticulation versus insufficient lineage sorting for the entire complex. However, there is firm evidence that S. flavus subsp. breviflorus and S. rupestris have acquired cpDNA haplotypes and ITS sequences from co-occurring species by reticulation. In contrast, insufficient lineage sorting is a viable hypothesis for cpDNA haplotypes shared between S. gallicus and its close relatives. We estimated the minimum coalescent times for these haplotypes by utilizing the inferred species phylogeny and associated divergence times. Our data suggest that ancestral cpDNA polymorphisms may have survived for ca. 0.4-1.0 million years, depending on molecular clock calibrations. PMID- 11761057 TI - Down the tube: pollinators, predators, and the evolution of flower shape in the alpine skypilot, Polemonium viscosum. AB - We address how a conflict between pollinator attraction and avoidance of flower predation influences the evolution of flower shape in Polemonium viscosum. Flower shape in P. viscosum is the product of an isometric relationship between genetically correlated (rA = 0.70) corolla flare and length. Bumblebee pollinators preferentially visit flowers that are more flared and have longer tubes, selecting for a funnel-shaped corolla. However, flower shape also influences nectar-foraging ants that sever the style at its point of attachment to the ovary. Surveys of ant damage show that plants having flowers with flared, short corollas are most vulnerable to ant predation. Consistent with this result, the ratio of corolla length to flare is significantly greater in a krummholz (high predation risk) population than in a tundra (low predation risk) population. To explicitly test whether the evolution of a better defended flower would exact a cost in pollination, we created tubular flowers by constricting the corolla during development. Performance of tubular flowers and natural controls was compared for defensive and attractive functions. In choice trials, ants entered control flowers significantly more often than tubular ones, confirming that the evolution of tubular flowers would reduce the risk of predation. However, in a bumblebee-pollinated population, tubular flowers received significantly less pollen and set fewer seeds than controls. A fitness model incorporating these data predicts that in the absence of the genetic correlation between corolla length and flare, intermittent selection for defense could allow tubular flowers to spread in the krummholz population. However, in the tundra, where bumblebees account for nearly all pollination, the model predicts that tubular flowers should always confer a fitness disadvantage. PMID- 11761058 TI - Gene flow versus local adaptation in the northern acorn barnacle, Semibalanus balanoides: insights from mitochondrial DNA variation. AB - In reciprocal transplant experiments, Bertness and Gaines (1993) found that Semibalanus balanoides juveniles that had settled in an upper Narragansett Bay estuary survived better in that estuary that did juveniles from coastal localities. The observed pattern of survivorship led to the claim that local adaptation may result from a combination of limited gene flow between and strong selection within these habitats. Here we test the hypothesis that limited gene flow has led to habitat-specific population differentiation using sequence and restriction fragment length polymorphism analyses of the mitochondrial DNA D-loop region of S. balanoides. Samples were analyzed from replicated coastal and estuary localities in both Narragansett Bay, Rhode Island, and Damariscotta River, Maine. The patterns of F(ST) indicate that gene flow between coast and estuary is extensive (Nm > 100) and is not lower in the estuary with lower flushing rates (Narragansett Bay). Given the high estimate of genetic exchange, adaptations for unpredictable environments seem more likely than local adaptation in this species because loci that respond to selection in one generation are essentially homogenized by the next seasons' settlement. Nevertheless, these estimates of neutral gene flow can help identify the strength of selection necessary for local adaptation to accumulate in Semibalanus. PMID- 11761059 TI - Partial incompatibility between ants and symbiotic fungi in two sympatric species of Acromyrmex leaf-cutting ants. AB - We investigate the nature and duration of incompatibility between certain combinations of Acromyrmex leaf-cutting ants and symbiotic fungi, taken from sympatric colonies of the same or a related species. Ant-fungus incompatibility appeared to be largely independent of the ant species involved, but could be explained partly by genetic differences among the fungus cultivars. Following current theoretical considerations, we develop a hypothesis, originally proposed by S. A. Frank, that the observed incompatibilities are ultimately due to competitive interactions between genetically different fungal lineages, and we predict that the ants should have evolved mechanisms to prevent such competition between cultivars within a single garden. This requires that the ants are able to recognize unfamiliar fungi, and we show that this is indeed the case. Amplified fragment length polymorphism genotyping further shows that the two sympatric Acromyrmex species share each other's major lineages of cultivar, confirming that horizontal transfer does occasionally take place. We argue and provide some evidence that chemical substances produced by the fungus garden may mediate recognition of alien fungi by the ants. We show that incompatibility between ants and transplanted, genetically different cultivars is indeed due to active killing of the novel cultivar by the ants. This incompatibility disappears when ants are force-fed the novel cultivar for about a week, a result that is consistent with our hypothesis of recognition induced by the resident fungus and eventual replacement of incompatibility compounds during force-feeding. PMID- 11761060 TI - Seasonally varying diet quality and the quantitative genetics of development time and body size in birch feeding insects. AB - Genetic variance-covariance structures (G), describing genetic constraints on microevolutionary changes of populations, have a central role in the current theories of life-history evolution. However, the evolution of Gs in natural environments has been poorly documented. Resource quality and quantity for many animals and plants vary seasonally, which may shape genetic architectures of their life histories. In the mountain birch-insect herbivore community, leaf quality of birch for insect herbivores declines profoundly during both leaf growth and senescence, but remains stable during midsummer. Using six sawfly species specialized on the mountain birch foliage, we tested the ways in which the seasonal variation in foliage quality of birch is related to the genetic architectures of larval development time and body size. In the species consuming mature birch leaves of stable quality, that is, without diet-imposed time constraints for development time, long development led to high body mass. This was revealed by the strongly positive phenotypic and genetic correlations between the traits. In the species consuming growing or senescing leaves, on the other hand, the rapidly deteriorating leaf quality prevented the larvae from gaining high body mass after long development. In these species, the phenotypic and genetic correlations between development time and final mass were negative or zero. In the early-summer species with strong selection for rapid development, genetic variation in development time was low. These results show that the intuitively obvious positive genetic relationship between development time and final body mass is a probable outcome only when the constraints for long development are relaxed. Our study provides the first example of a modification in guild-wide patterns in the genetic architectures brought about by seasonal variation in resource quality. PMID- 11761061 TI - Host-induced assortative mating in host races of the larch budmoth. AB - The likelihood of sympatric speciation is enhanced when assortative mating is a by-product of adaptation to different habitats. Pleiotropy of this kind is recognized as important in parasites that use their hosts as a long-range cue for finding mates, but is generally assumed to have limited applicability for most other organisms. In the larch budmoth, Zeiraphera diniana (Lepidoptera: Tortricidae), sympatric host races feed on larch or pine. Zeiraphera diniana females attract males (call) by releasing host-independent long-range pheromones. Pheromone composition differs strongly between host races, but we show in an experimental field study that cross-attraction can occur at a rate of 0.03-0.38. Cross-attraction to larch females increases when they call from neighborhoods (8 m radius) rich in pine or from pine trees. Cross-attraction to pine females similarly increases when calling from neighborhoods rich in larch, but there is no significant effect of calling substrate. Males, as well as females, of this species preferentially alight on their own host, and in neighborhoods where their own host is common. This effect of tree species and host neighborhood on assortative mating is therefore due, at least in part, to the numbers of males of each host race present within approximately 200 m2 surrounding the female. This proximity effect is enhanced by the clumped distributions of the hosts themselves. Host chemistry might also affect pheromone production and/or response directly, but we have evidence neither for nor against this. This work provides empirical evidence that host adaptation has a pleiotropic effect on assortative mating in a species with host-independent long-range mating signals. Sympatric speciation via pleiotropy between ecological traits and assortative mating may thus be more common than generally supposed: Clumped resource distributions and habitat choice by adults are widespread. PMID- 11761063 TI - The role of introgressive hybridization in the evolution of the Gila robusta complex (Teleostei: Cyprinidae). AB - The extent and impact of introgressive hybridization was examined in the Gila robusta complex of cyprinid fishes using mitochondrial DNA (mtDNA) sequence variation. Lower Colorado River basin populations of G. robusta, G. elegans, and G. cypha exhibited distinct mtDNAs, with only limited introgression of G. elegans into G. cypha. The impact of hybridization was significant in upper Colorado River basin populations; most upper basin fishes sampled exhibited only G. cypha mtDNA haplotypes, with some individuals exhibiting mtDNA from G. elegans. The complete absence of G. robusta mtDNA, even in populations of morphologically pure G. robusta, indicates extensive introgression that predates human influence. Analysis of the geographic distribution of variation identified two distinctive G. elegans lineages; however, the small number of individuals and localities sampled precluded a comprehensive analysis. Analysis of haplotype and population networks for G. cypha mtDNAs from 15 localities revealed low divergence among haplotypes; however, significant frequency differences among populations within and among drainages were found, largely attributable to samples in the Little Colorado River region. This structure was not associated with G. cypha and G. robusta, as morphotypes from the same location are more similar than conspecific forms in other locations. This indicates that morphological and mtDNA variation are affected by different evolutionary forces in Colorado River Gila and illustrates how both hybridization and local adaptation can play important roles in evolution. PMID- 11761062 TI - The evolution of agriculture in beetles (Curculionidae: Scolytinae and Platypodinae). AB - Beetles in the weevil subfamilies Scolytinae and Platypodinae are unusual in that they burrow as adults inside trees for feeding and oviposition. Some of these beetles are known as ambrosia beetles for their obligate mutualisms with asexual fungi--known as ambrosia fungi--that are derived from plant pathogens in the ascomycete group known as the ophiostomatoid fungi. Other beetles in these subfamilies are known as bark beetles and are associated with free-living, pathogenic ophiostomatoid fungi that facilitate beetle attack of phloem of trees with resin defenses. Using DNA sequences from six genes, including both copies of the nuclear gene encoding enolase, we performed a molecular phylogenetic study of bark and ambrosia beetles across these two subfamilies to establish the rate and direction of changes in life histories and their consequences for diversification. The ambrosia beetle habits have evolved repeatedly and are unreversed. The subfamily Platypodinae is derived from within the Scolytinae, near the tribe Scolytini. Comparison of the molecular branch lengths of ambrosia beetles and ambrosia fungi reveals a strong correlation, which a fungal molecular clock suggests spans 60 to 21 million years. Bark beetles have shifted from ancestral association with conifers to angiosperms and back again several times. Each shift to angiosperms is associated with elevated diversity, whereas the reverse shifts to conifers are associated with lowered diversity. The unusual habit of adult burrowing likely facilitated the diversification of these beetle fungus associations, enabling them to use the biomass-rich resource that trees represent and set the stage for at least one origin of eusociality. PMID- 11761064 TI - Social causes of correlational selection and the resolution of a heritable throat color polymorphism in a lizard. AB - When selection acts on social or behavioral traits, the fitness of an individual depends on the phenotypes of its competitors. Here, we describe methods and statistical inference for measuring natural selection in small social groups. We measured selection on throat color alleles that arises from microgeographic variation in allele frequency at natal sites of side-blotched lizards (Uta stansburiana). Previous game-theoretic analysis indicates that two color morphs of female side-blotched lizards are engaged in an offspring quantity-quality game that promotes a density- and frequency-dependent cycle. Orange-throated females are r-strategists. They lay large clutches of small progeny, which have poor survival at high density, but good survival at low density. In contrast, yellow throated females are K-strategists. They lay small clutches of large progeny, which have good survival at high density. We tested three predictions of the female game: (1) orange progeny should have a fitness advantage at low density; (2) correlational selection acts to couple color alleles and progeny size; and (3) this correlational selection arises from frequency-dependent selection in which large hatchling size confers an advantage, but only when yellow alleles are rare. We also confirmed the heritability of color, and therefore its genetic basis, by producing progeny from controlled matings. A parsimonious cause of the high heritability is that three alleles (o, b, y) segregate as one genetic factor. We review the physiology of color formation to explain the possible genetic architecture of the throat color trait. Heritability of color was nearly additive in our breeding study, allowing us to compute a genotypic value for each individual and thus predict the frequency of progeny alleles released on 116 plots. Rather than study the fitness of individual progeny, we studied how the fitness of their color alleles varied with allele frequency on plots. We confirmed prediction 1: When orange alleles are present in female progeny, they have higher fitness at low density when compared to other alleles. Even though the difference in egg size of the female morphs was small (0.02 g), it led to knife-edged survival effects for their progeny depending on local social context. Selection on hatchling survival was not only dependent on color alleles, but on a fitness interaction between color alleles and hatchling size, which confirmed prediction 2. Sire effects, which are not confounded by maternal phenotype, allowed us to resolve the frequency dependence of correlational selection on egg size and color alleles and thereby confirmed prediction 3. Selection favored large size when yellow sire alleles were rare, but small size when they were common. Correlational selection promotes the formation of a self-reinforcing genetic correlation between the morphs and life-history variation, which causes selection in the next density and frequency cycle to be exacerbated. We discuss general conditions for the evolution of self-reinforcing genetic correlations that arise from social selection associated with frequency-dependent sexual and natural selection. PMID- 11761065 TI - Condition, genotype-by-environment interaction, and correlational selection in lizard life-history morphs. AB - We compared reproductive allocation and variation in condition and survivorship of two heritable female throat color morphs (orange and yellow) in a free-living population of side-blotched lizards (Uta stansburiana). Using path analysis and structural equation modeling, we investigated how variation in the social environment affected clutch size and egg mass and two condition traits (postlaying mass, immunological condition) and how these traits in turn affected female field survival. In the presence of many neighbors, both morphs increased their clutch sizes, although these effects were only significant in yellow females. In addition, yellow females increased their egg mass in the presence of many orange neighbors. Orange females surrounded by many orange neighbors showed sign of stress in the form of immunosuppression, whereas this effect was less pronounced in yellow females. The morphs also differed in the impact of variation in clutch size and egg mass on both condition traits. Finally, female morphotype and immune responsiveness affected fitness interactively, and hence these two traits showed signs of fitness epistasis: Selection gradients on this trait were opposite in sign in the two morphs. The correlational selection gradient (gamma throat x antibody response) between female throat color and antibody responsiveness was -0.365. Our data thus reveal important interactive effects such as genotype-by-environment interaction toward the social environment and morph-specific trade-offs as well as the occurrence of correlational selection. We discuss the use of naturally occurring and conspicuous genetic polymorphisms in field studies of selection and life-history allocation. PMID- 11761066 TI - Evolutionary implications of divergent clines in an avian (Manacus: Aves) hybrid zone. AB - A previous study of the hybrid zone in western Panama between white-collared (Manacus candei) and golden-collared manakins (M. vitellinus) documented the unidirectional introgression of vitellinus male secondary sexual traits across the zone. Here, we examine the hybrid zone in greater genetic and morphological detail. Statistical comparisons of clines are performed using maximum-likelihood and nonparametric bootstrap methods. Our results demonstrate that an array of six molecular and two morphometric markers agree in cline position and width. Clines for male collar and belly color are similar in width to the first eight clines, but are shifted in position by at least five cline widths. The result is that birds in intervening populations are genetically and morphometrically very like parental candei, but males have the plumage color of parental vitellinus. Neither neutral diffusion nor nonlinearity of color scales appear to be viable explanations for the large cline shifts. Genetic dominance of vitellinus plumage traits is another potential explanation that will require breeding experiments to test. Sexual selection remains a plausible explanation for the observed introgression of vitellinus color traits in these highly dimorphic, polygynous, lek-mating birds. Two other clines, including a nondiagnostic isozyme locus, are similar in position to the main cluster of clines, but are broader in width. Thus, introgression at some loci is greater than that detected with diagnostic markers. Assuming that narrow clines are maintained by selection, variation in cline width indicates that selection is not uniform throughout the genome and that diagnostic markers are under more intense selective pressure. The traditional focus on diagnostic markers in studies of hybrid zones may therefore lead to underestimates of average introgression. This effect may be more pronounced in organisms with low levels of genetic divergence between hybridizing taxa. PMID- 11761067 TI - Shifts in bilateral asymmetry within a distribution range: the case of the chukar partridge. AB - Three major types of bilateral asymmetry (fluctuating asymmetry, directional asymmetry, and antisymmetry) have long been recognized in the literature. Little, however, is known about transitions between asymmetry types, especially in natural populations. It is often assumed that directional asymmetry and antisymmetry have a larger genetic basis than fluctuating asymmetry. This leads many scientists to exclude traits or populations showing either directional asymmetry or antisymmetry from developmental instability studies, focusing attention on fluctuating asymmetry alone. This procedure may bias the findings and thus our understanding of patterns of bilateral asymmetry and the factors influencing it. To examine changes in bilateral asymmetry across the distribution range of a species, I studied the length of the third toe in 11 chukar partridge (Alectoris chukar) populations across a steep environmental gradient of 320 km within the species' range in Israel. This trait was selected due to its adaptive value in the chukar, a species that spends much of its activity walking, and due to its high measurement repeatability. Moving from the core toward the very extreme periphery of the range, the following four trends are detected: (1) the expression of the directional asymmetry component significantly increases; (2) the frequency of symmetrical individuals in the population significantly decreases, with a sharp decline at the steepest part of the climatic and environmental gradient studied, within the Mediterranean-desert ecotone; (3) mean asymmetry levels, as estimated using the unsigned difference between the right and left toe, significantly increases; and (4) the range of asymmetry increases such that the most asymmetrical individuals originate from the very edge of the range. These findings provide primary evidence that substantial shifts in asymmetry may occur across short geographical distances within a species' distribution range. They show a continuum between asymmetry types and support the notion that all three types of asymmetry can reflect developmental instability. Further studies of developmental instability should be designed so that they enable detection of transitions between asymmetry types across natural populations. Such a procedure may partly resolve some of the contradictions seen in the literature regarding the relationship between bilateral asymmetry and environmental stress. PMID- 11761068 TI - Albinism and phenotype of barn swallows (Hirundo rustica) from Chernobyl. AB - The effects of mutation on phenotypic expression are supposed to be mainly deleterious because mutations disrupt the expression of genes that function relatively well under current environmental conditions. Thus, mutations are assumed to give rise to deviant phenotypes that are generally selected against. Radioactive contamination in the Chernobyl region of Ukraine is associated with a significant increase by a factor two to 10 in mutation rate in microsatellite markers of the barn swallow, Hirundo rustica. Barn swallows from Chernobyl had a temporally constant, elevated frequency of partial albinism compared to the situation before radioactive contamination and compared to birds from a control area. Albinism disproportionately affected the carotenoid-based plumage of the head, suggesting that carotenoid metabolism is particularly susceptible to the effects of radiation. Individuals with partially albinistic plumage had, on average, lower mean phenotypic values than other birds, and this was particularly the case for males. Furthermore, differences in phenotypic variation, as determined using Levene's test, were significantly larger in partial albinos compared to nonalbinos in males, but not in females, even though the null expectation would be the opposite due to the lower mean phenotypic values of partial albinos. Although small phenotypes were commonly associated with germline mutations, there was no general decrease in overall body size during the period 1991-2000, implying that small individuals were selected against. Because partial albinism is disfavored by natural selection, the effects of mutations are deleterious, giving rise to a balance between mutation and selection. PMID- 11761069 TI - Sex-biased gene flow in spectacled eiders (Anatidae): inferences from molecular markers with contrasting modes of inheritance. AB - Genetic markers that differ in mode of inheritance and rate of evolution (a sex linked Z-specific microsatellite locus, five biparentally inherited microsatellite loci, and maternally inherited mitochondrial [mtDNA] sequences) were used to evaluate the degree of spatial genetic structuring at macro- and microgeographic scales, among breeding regions and local nesting populations within each region, respectively, for a migratory sea duck species, the spectacled eider (Somateria fisheri). Disjunct and declining breeding populations coupled with sex-specific differences in seasonal migratory patterns and life history provide a series of hypotheses regarding rates and directionality of gene flow among breeding populations from the Indigirka River Delta, Russia, and the North Slope and Yukon-Kuskokwim Delta, Alaska. The degree of differentiation in mtDNA haplotype frequency among breeding regions and populations within regions was high (phiCT = 0.189, P < 0.01; phiSC = 0.059, P < 0.01, respectively). Eleven of 17 mtDNA haplotypes were restricted to a single breeding region. Genetic differences among regions were considerably lower for nuclear DNA loci (sex linked: phiST = 0.001, P > 0.05; biparentally inherited microsatellites: mean theta = 0.001, P > 0.05) than was observed for mtDNA. Using models explicitly designed for uniparental and biparentally inherited genes, estimates of spatial divergence based on nuclear and mtDNA data together with elements of the species' breeding ecology were used to estimate effective population size and degree of male and female gene flow. Differences in the magnitude and spatial patterns of gene correlations for maternally inherited and nuclear genes revealed that females exhibit greater natal philopatry than do males. Estimates of generational female and male rates of gene flow among breeding regions differed markedly (3.67 x 10(-4) and 1.28 x 10(-2), respectively). Effective population size for mtDNA was estimated to be at least three times lower than that for biparental genes (30,671 and 101,528, respectively). Large disparities in population sizes among breeding areas greatly reduces the proportion of total genetic variance captured by dispersal, which may accelerate rates of inbreeding (i.e., promote higher coancestries) within populations due to nonrandom pairing of males with females from the same breeding population. PMID- 11761070 TI - Positive genetic correlation between parasite resistance and body size in a free living ungulate population. AB - Parasite resistance and body size are subject to directional natural selection in a population of feral Soay sheep (Ovis aries) on the island of St. Kilda, Scotland. Classical evolutionary theory predicts that directional selection should erode additive genetic variation and favor the maintenance of alleles that have negative pleiotropic effects on other traits associated with fitness. Contrary to these predictions, in this study we show that there is considerable additive genetic variation for both parasite resistance, measured as fecal egg count (FEC), and body size, measured as weight and hindleg length, and that there are positive genetic correlations between parasite resistance and body size in both sexes. Body size traits had higher heritabilities than parasite resistance. This was not due to low levels of additive genetic variation for parasite resistance, but was a consequence of high levels of residual variance in FEC. Measured as coefficients of variation, levels of additive genetic variation for FEC were actually higher than for weight or hindleg length. High levels of additive genetic variation for parasite resistance may be maintained by a number of mechanisms including high mutational input, balancing selection, antagonistic pleiotropy, and host-parasite coevolution. The positive genetic correlation between parasite resistance and body size, a trait also subject to sexual selection in males, suggests that parasite resistance and growth are not traded off in Soay sheep, but rather that genetically resistant individuals also experience superior growth. PMID- 11761071 TI - Estimating genetic correlations from measurements of field-caught waterstriders. AB - Lynch (1999) proposed a method for estimation of genetic correlations from phenotypic measurements of individuals for which no pedigree information is available. This method assumes that shared environmental effects do not contribute to the similarity of relatives, and it is expected to perform best when sample sizes are large, many individuals in the sample are paired with close relatives, and heritability of the traits is high. We tested the practicality of this method for field biologists by using it to estimate genetic correlations from measurements of field-caught waterstriders (Aquarius remigis). Results for sample sizes of less than 100 pairs were often unstable or undefined, and even with more than 500 pairs only half of those correlations that had been found to be significant in standard laboratory experiments were statistically significant in this study. Statistically removing the influence of environmental effects (shared between relatives) weakened the estimates, possibly by removing some of the genetic similarity between relatives. However, the method did generate statistically significant estimates for some genetic correlations. Lynch (1999) anticipated the problems found, and proposed another method that uses estimates of relatedness between members of pairs (from molecular marker data) to improve the estimates of genetic correlations, but that approach has yet to be tested in the field. PMID- 11761072 TI - Reproductive skew and split sex ratios in social Hymenoptera. AB - I present a model demonstrating that, in social Hymenoptera, split sex allocation can influence the evolution of reproductive partitioning (skew). In a facultatively polygynous population (with one to several queens per colony), workers vary in their relative relatedness to females (relatedness asymmetry). Split sex-ratio theory predicts that workers in monogynous (single-queen) colonies should concentrate on female production, as their relatedness asymmetry is relatively high, whereas workers in the polygynous colonies should concentrate on male production, as their relatedness asymmetry is relatively low. By contrast, queens in all colonies value males more highly per capita than they value females, because the worker-controlled population sex ratio is too female biased from the queens' standpoint. Consider a polygynous colony in a facultatively polygynous population of perennial, social Hymenoptera with split sex ratios. A mutant queen achieving reproductive monopoly would gain from increasing her share of offspring but, because the workers would assess her colony as monogynous, would lose from the workers rearing a greater proportion of less-valuable females from the colony's brood. This sets an upper limit on skew. Therefore, in social Hymenoptera, skew evolution is potentially affected by queen worker conflict over sex allocation. PMID- 11761073 TI - Rapid measurement of deuterium content of breath following oral ingestion to determine body water. AB - The ability to measure total body water accurately, non-invasively and rapidly with results that are immediately available would represent an important advance in body composition research. Flowing afterglow mass spectrometry (FA-MS) has been developed to enable immediate measurement of deuterium content in breath water from single exhalations, which when combined with oral D2O loading enables measurement of total body water. We report here its first use in normal subjects, demonstrating the dispersal kinetics of deuterium in the body by monitoring deuterium in breath water following ingestion. Ten studies were performed in six normal subjects. After obtaining baseline samples, each subject ingested 0.3 g x kg(-1) of 99.9% pure D2O. Subsequently, breath samples were obtained every 3-5 minutes until equilibration had occurred. Three distinct phases in breath deuterium content were observed: an initial immediate peak due to HDO remaining in the oral cavity, a secondary peak reflecting gastrointestinal absorption and finally equilibration with the body water. The incremental increase in breath deuterium abundance between baseline and equilibration was used to calculate the total body water. Mathematical fitting of this final equilibration phase demonstrated that the measured deuterium abundance was within 0.2% of the ideal (asymptotic) value within 2 hours in all cases. We conclude that FA-MS is a powerful new method that, when combined with oral D2O loading, enables measurement of the dispersal kinetics of HDO and the calculation of total body water within 2 hours. PMID- 11761074 TI - Reproducibility of a non-invasive real-time measure of cardiac parasympathetic activity. AB - The NeuroScope is a new device which produces a continuous real-time index of cardiac parasympathetic activity (the CIPA) and accurately measures RR intervals. The reproducibility of the CIPA has not yet been assessed. This study was designed to assess the reproducibility of a 5 minute recording of the CIPA using the NeuroScope and compare it with that of conventional heart rate variability (HRV) measures. 50 subjects (31 male, 19 female) aged 21-77 years were recruited. 11 of these were apparently healthy and 39 were patients with a variety of cardiological problems. Two 5 minute recordings of CIPA and RR intervals for each subject were made with a 2-3 minute break between recordings. The limits of agreement for the CIPA were such that the second estimate was between 72 and 140% of the first estimate, 95% of the time. The limits of agreement for other indices of HRV, namely SDNN, rMSSD, In low-frequency HRV and In high-frequency HRV, were 61-157%, 68-153%, 77-131% and 76-133%. The short-term reproducibility of a 5 minute recording of CIPA is moderate and better than simple time-domain but not frequency-domain measures of HRV. PMID- 11761075 TI - A digital system for recording the electrical activity of the uterus. AB - The ability to identify true pre-term labour would be of considerable clinical benefit as electrical signals from the uterus, recorded using surface electrodes, may discriminate between labouring and non-labouring states in human pregnancy. A digital recording system for recording the electrical activity of the uterus has been developed and is described in this paper. A pilot study in which entire recordings in 21 women were subjected to power spectral analysis suggests that the relative power in two frequency bands (0.2-0.45 Hz and 0.8-3 Hz) changes as pregnancy progresses into early labour. PMID- 11761076 TI - High-resolution speckle-microscopy: study of the spatial structure of a bioflow. AB - Perspectives of velocity measurements of a random bioflow and its spatial structure by speckle-methods are studied in this paper. The mechanism of output signal formation and the optical scheme of the speckle-microscope are described. Amplitude, phase and frequency characteristics of this measuring system are investigated. The main types of signal distortions in the speckle-microscope are considered. Results of the analysis of output characteristics are applied to measurements of the spatial distribution of the refractive index of a blood flow in a small single microvessel. It is shown that the minimal size of flow inhomogeneities (with fluctuations in the optical path of the investigated object, less than 0.01 lambda) that can be resolved by the speckle-microscope is about a quarter of the waist beam diameter. PMID- 11761077 TI - A method to standardize a reference of scalp EEG recordings to a point at infinity. AB - The effect of an active reference in EEG recording is one of the oldest technical problems in EEG practice. In this paper, a method is proposed to approximately standardize the reference of scalp EEG recordings to a point at infinity. This method is based on the fact that the use of scalp potentials to determine the neural electrical activities or their equivalent sources does not depend on the reference, so we may approximately reconstruct the equivalent sources from scalp EEG recordings with a scalp point or average reference. Then the potentials referenced at infinity are approximately reconstructed from the equivalent sources. As a point at infinity is far from all the possible neural sources, this method may be considered as a reference electrode standardization technique (REST). The simulation studies performed with assumed neural sources included effects of electrode number, volume conductor model and noise on the performance of REST, and the significance of REST in EEG temporal analysis. The results showed that REST is potentially very effective for the most important superficial cortical region and the standardization could be especially important in recovering the temporal information of EEG recordings. PMID- 11761078 TI - Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode. AB - The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration. A computer program has been used to simulate the vascular structure of various tissues and also the measurements of oxygen tension using a polarographic electrode. The electrode absorption process is described using a theoretical model. The gradient of oxygen in tissue is described by a mathematical model that takes into consideration both diffusion and cellular consumption of oxygen. We have compared the results obtained using the response function of the electrode and some simplifications of it. The results of these comparisons show that there are some differences in the 'observed' distributions of the oxygen tension in tissues predicted using different formulae for the electrode response function. Also, there are considerable differences between the input oxygen distribution and the measured values in all cases. All the results of the simulations of the oxygen tension 'observed' by a 12 microm polarographic electrode, using different response functions of the electrode, show that the electrode averages the values from many cells. Care should be taken in using a simplification for the response function of the electrode, especially if the results are going to be used as input values in modelling the tumour response to new treatments and/or as a basis of selecting patients for treatments. A computer simulation of measurement of oxygen tensions in regions of steep pO2 gradients shows that extremely high and extremely low pO2 values will not be detected. PMID- 11761079 TI - Mathematical modelling of responses of cerebral blood vessels to changing intraluminal pressure. AB - The authors have designed a mathematical model to investigate the influences of the physical and chemical properties of the cerebral blood vessel resistance on vessel diameter. The model is based on the way the total tension within the blood vessel walls varies due to specific ions interacting and affecting the vascular smooth muscle cells and the vascular walls. In particular, we shall model a series of calcium sites and derive a generalized equation of the diameter as a function of pressure. The model includes the action of the vascular smooth muscle cells and the elasticity of the vascular walls, the pressure exerted on the walls by the blood and the effect of alterations to their properties within the blood vessel. They are formulated in terms of three parameters: the diameter at zero pressure, the myogenic response as the pressure tends to zero and a term associated with the myogenic tone. All three parameters may be reliably extracted from diameter-pressure measurements. The model was successfully used in quantifying diameter oscillations and dynamic myogenic responses that are frequently observed both in vivo and in vitro. Finally, we tested the model on experimental data obtained from the resistance of cerebral vessels that have been isolated from rats. In particular, we have first shown that the blood vessel characteristics are such that the diameter change due to calcium ion variations is at a maximum value. Second, we have shown that blood flow affects the myogenic response and third, we can explain the affect of ATP on the vessel diameter. PMID- 11761080 TI - Empirical estimators of gamma fits to tracer-dilution curves and their technical basis and practical scope. AB - A gamma fit facilitates smoothing and extrapolation of distorted tracer-dilution curves in blood flow studies. Theoretically based empirical estimators were developed as simple alternatives to direct regression approaches from simulated gamma distributions with a wide range of shape asymmetry. Key curve features of peak height p, full width w at half peak height, rising and falling limb inflection tangents and asymmetry of the peak time with respect to the p/2 height occurrences were related to the parameters of the distribution by multiple linear regression after suitable transformations. The product pw was simply related to the total area A under the curve, pw/A being 0.93 +/- 0.01 in 70 cardiac output determinations from ten surgical patients. Shape and scale parameters were closely related to the standard deviation, inflection point properties and w for the curves. Mensuration devices suitable for cardiac output computers were developed that calculated total areas from incomplete portions under gamma curves and by-passed the need for parameter estimation. There was limited point in estimating the distribution parameters just to derive particle transit times, because of the ad hoc nature of the fitting form, which did not allow for the back-dispersion by Brownian motion of tracer molecules diluting in blood flow. Nonetheless, the accuracy of area prediction using a gamma fit was adequate for most clinical purposes and comparable to that via the random walk function, giving good insight to established results and computing procedures. PMID- 11761081 TI - Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. AB - Laser Doppler velocimetry uses the frequency shift produced by the Doppler effect to measure velocity. It can be used to monitor blood flow or other tissue movement in the body. Laser speckle is a random interference effect that gives a grainy appearance to objects illuminated by laser light. If the object consists of individual moving scatterers (such as blood cells), the speckle pattern fluctuates. These fluctuations provide information about the velocity distribution of the scatterers. It can be shown that the speckle and Doppler approaches are different ways of looking at the same phenomenon. Both these techniques measure at a single point. If a map of the velocity distribution is required, some form of scanning must be introduced. This has been done for both time-varying speckle and laser Doppler. However, with the speckle technique it is also possible to devise a full-field technique that gives an instantaneous map of velocities in real time. This review article presents the theory and practice of these techniques using a tutorial approach and compares the relative merits of the scanning and full-field approaches to velocity map imaging. The article concludes with a review of reported applications of these techniques to blood perfusion mapping and imaging. PMID- 11761083 TI - MAST system: a new condensed cardiopulmonary bypass circuit for adult cardiac surgery. AB - There have been many refinements in cardiopulmonary bypass (CPB) techniques over the past few decades specific to design, materials and function. Despite these improvements, use of the standard length circuit tubing and pump oxygenator alter cellular, biochemical and rheological properties by inducing a systemic inflammatory response, persisting well into the early postoperative phase. We have designed a new condensed CPB circuit, the MAST system, where the oxygenator and the pumps are brought closer to the operating table (within 30 inches) with the help of a series of telescopic swivel steel poles to which they are attached. The control console is retained at the usual remote location of 2ft behind the MAST system. This configuration accomplishes a decrease in tubing length, priming volume and blood circulatory time within the extracorporeal circuit. Early experience of a hundred consecutive cases utilizing the MAST CPB system is presented along with a comparative analysis of prime volume, hemodilution and transfusion parameters of MAST system vs the low prime system, which is another newly developed CPB circuit utilizing a pediatric oxygenator to reduce prime volume and hemodilution. PMID- 11761082 TI - The use of leucocyte-depleting and conventional arterial line filters in cardiac surgery: a systematic review of clinical studies. AB - Although various forms of arterial line filter have been available for use during cardiopulmonary bypass (CPB) for 30 years, their use is not universal. The aim of this review was to seek evidence of the clinical benefit of using conventional or leucocyte-depleting arterial line filters during bypass. A literature search revealed 28 relevant clinical studies. Despite the wide variety of patient populations, types of filter and outcome measures utilized in studies, a few conclusions are possible. Whereas conventional filtration has the definite effect of reducing neuropsychological deficit post-CPB, the results of studies using the leucocyte-depleting filter are less clear cut. Leucocyte-depleting filters have potential for reducing inflammatory mediated heart and lung injury, however it is recommended that any additional benefit of leucocyte-depleting filters over conventional filters should be further tested by randomized controlled trials of sufficient size. PMID- 11761084 TI - A mobile system for the treatment of accidental hypothermia with extracorporeal circulation. AB - When deep accidental hypothermia causes circulatory failure, the best chance of survival is treatment with extracorporeal circulation (ECC) and warming of the blood. This may be difficult to achieve if the patient is first admitted to a hospital without a department of thoracic surgery. Our aim was to test a lightweight mobile system for ECC. The equipment could be transported almost anywhere, making it possible to start ECC on the spot and during transfer. The system was tested on six hypothermic pigs, two of the pigs at the institute laboratory, two of the pigs in a normal ambulance, and two of the pigs in an air force rescue helicopter. All of the pigs were transported back to the institute for warming to normal temperature. After warming, and the ECC stopped, all the pigs were in sinus rhythm and had an obviously satisfactory circulation. It is possible to bring a lightweight ECC system to the unstable patient. Treatment is possible in any hospital, ambulance or helicopter. PMID- 11761085 TI - Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal. AB - The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT < 200s, n =7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface. Mean ACTs were significantly different, as expected (HD: 446 +/- 26s, LD: 213 +/- 12s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep. PMID- 11761086 TI - Thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation. AB - The object was to study thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation (ECMO) and determine whether abnormal thyroid function correlates with prognosis. Total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), reverse triiodothyronine (rT3), thyroid-stimulating hormone, and thyroxine binding globulin were measured in 14 newborn infants with severe respiratory failure (age 1-30 days) from samples collected before anesthesia for cannula placement, at 30, 60, and 360 min after initiation of ECMO, and on days 2, 4, 6, and 8. The patients were divided into survivors and non-survivors for statistical analyses. No differences were noted between survivors and non-survivors in the pre-ECMO mean serum concentrations of the thyroid function tests analyzed. In nine survivors, mean serum T4, FT4, T3, FT3, and rT3 all declined significantly within 30-60 min after initiation of ECMO, compared to baseline values. The values for all mean serum concentrations recovered completely and exceeded baseline between days 2 and 8. In five non-survivors, the decline of all mean serum values was not statistically significant and recovery to baseline was not achieved. The ratios of mean serum concentration of rT3/FT3 were significantly different between survivors and non survivors across all times during the ECMO course (p < 0.0005). These findings indicate that abnormalities in thyroid function occur in neonates with severe respiratory failure on ECMO and that the rT3/FT3 ratio correlates with prognosis over the ECMO course. Survival was associated with a significant reduction of serum thyroid hormone concentrations followed by recovery. We speculate that, in neonates with respiratory failure on ECMO, adaptive mechanisms which enhance survival include the capacity to down-regulate the pituitary-thyroid axis. PMID- 11761087 TI - Factor V(LEIDEN) and cardiopulmonary bypass: investigation of haemostatic parameters and the effect of aprotinin using an ex vivo model. AB - It has been suggested that aprotinin results in significantly increased risk for perioperative thrombotic complications in patients with Factor V(LEIDEN) (F5L) due to its ability to competitively inhibit activated protein C (APC) function in vitro. No clinical studies have been performed to assess the effect of aprotinin on APC function of F5L in vivo. We developed an ex vivo model to mimic the effects of cardiopulmonary bypass with the exclusion of the patient in order to assess APC function. Blood from normal (n = 2) and F5L heterozygous donors (n = 2) was treated with aprotinin or placebo (saline). The blood was heparinized, added to the prime and circulated at 2 l/min through a modified cardiopulmonary bypass circuit. After 60 min of circulation, the heparin was neutralized with protamine sulfate. Blood samples, drawn at specific time points, were analysed for APC ratio. Results showed a decrease in APC ratio for both F5L and normal bloods with the addition of aprotinin (18% and 40%, respectively). APC ratios also decreased with the commencement of extracorporeal circulation for all bloods, resulting in an APC ratio of 1.35 in normal placebo-treated blood and 0.67 in F5L placebo-treated blood. The combined effect of aprotinin and extracorporeal circulation resulted in APC ratios of 0.90 for normal blood and 0.63 for F5L blood, corresponding to a severe dysfunction of APC intraoperatively (reference range 1.9-4.0). The data from this model predict an increased risk of perioperative thrombosis due to inhibition of APC function in cardiac surgical patients heterozygous for the F5L mutation. Aprotinin further compounds the severity of APC dysfunction, though the effect is more severe in normal blood. The ex vivo model employed was an effective tool for the investigation of the haemostatic effect of aprotinin. This model may be exploited for other applications such as the investigation of novel or emerging haemostatic agents prior to clinical trial. PMID- 11761088 TI - Use of desmopressin and erythropoietin in an anaemic Jehovah's Witness patient with severely impaired coagulation capacity undergoing stentless aortic valve replacement. AB - Cardiac surgery in Jehovah's Witness patients remains a challenge in the presence of concomitant congenital or acquired coagulation disorders and anaemia. We report a case of a 66-year-old female Jehovah's Witness suffering from severe calcified aortic valve stenosis requiring aortic valve replacement. The anaemic patient suffered from concomitant platelet dysfunction and deficiency of factors V and VII due to gammopathy of immunoglobulin G. The patient was preoperatively treated with recombinant erythropoietin in combination with folic acid and iron, which resulted in an increase of the haematocrit from 0.335 to 0.416 after 22 days of treatment. Haemostasis was improved by high dose aprotinin and additional desmopressin, which could be demonstrated to be effective by a preoperative test. The patients intra- and postoperative course was uneventful, her total chest tube loss was 130 ml, and she was able to be discharged without the need of any blood transfusions. The beneficial properties of erythropoietin and desmopressin in Jehovah's Witness patients are discussed. PMID- 11761089 TI - Apoptosis in the ischemic reperfused myocardium. AB - Recovery of the myocardium from an ischemic event depends on the reperfusion of the ischemic area. Resumed blood flow to the tissue restores the metabolic substrates necessary for energy production and cell survival. Paradoxically, ischemic reperfusion (I/R) can result in further damage to the myocardium (I/R injury) through an acute inflammatory response mediated by cytokines, neutrophils, macrophages, and reactive oxygen species. These events can trigger cardiomyocyte death through either necrosis or apoptosis. This report will focus on the apoptosis process, which is an organized, active, and gene-directed process of cell self-destruction that can be initiated by intracellular genetic programs, or second messenger pathways inside the cell upon extracellular stimulation by signaling molecules or stress. Awareness of the apoptotic process in cardiomyocytes and endothelial cells is relevant to myocardial preservation during cardiopulmonary bypass compared with off-pump cornary artery bypass procedures. Pharmacological interventions of the signaling pathways that control apoptosis provide an opportunity for new therapeutic approaches to reduce I/R injury in the heart. This review of apoptosis will introduce the perfusionist to apoptosis in the I/R heart, discuss some of the metabolic pathways that initiate it, and report on developing strategies to prevent it. PMID- 11761090 TI - Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C. AB - To investigate the influence of hypothermic cardiopulmonary bypass (HCPB) at 25 degrees C and circulatory arrest at 18 degrees C on the global and regional cerebral blood flow (CBF) during pulsatile perfusion, we performed the following studies in a neonatal piglet model. Using a pediatric physiologic pulsatile pump, we subjected six piglets to deep hypothermic circulatory arrest (DHCA) and six other piglets to HCPB. The DHCA group underwent hypothermia for 25 min, DHCA for 60min, cold reperfusion for 10 min, and rewarming for 40 min. The HCPB group underwent 15 min of cooling, followed by 60 min of HCPB, 10min of cold reperfusion, and 30 min of rewarming. The following variables remained constant in both groups: pump flow (150 ml/kg/min), pump rate (150 bpm), and stroke volume (1 ml/kg). During the 60-min aortic crossclamp period, the temperature was kept at 18 degrees C for DHCA and at 25 degrees C for HCPB. The global and regional CBF (ml/100g/min) was assessed with radiolabeled microspheres. The CBF was 48% lower during deep hypothermia at 18degrees C (before DHCA) than during hypothermia at 25 degrees C (55.2 +/- 14.3ml/100g/min vs 106.4 +/- 19.7 ml/100 g/min; p < 0.05). After rewarming, the global CBF was 45% lower in the DHCA group than in the HCPB group 48.3 +/- 18.1 ml/100g/min vs (87 +/- 35.9ml/100g/min; p < 0.05). Fifteen minutes after the termination of CPB, the global CBF was only 25% lower in the DHCA group than in the HCPB group (42.2 +/- 20.7 ml/100 g/min vs 56.4 +/- 25.8ml/100g/min; p = NS). In the right and left hemispheres, cerebellum, basal ganglia, and brain stem, blood flow resembled the global CBF. In conclusion, both HCPB and DHCA significantly decrease the regional and global CBF during CPB. Unlike HCPB, DHCA has a continued negative impact on the CBF after rewarming. However, 15 min after the end of CPB, there are no significant intergroup differences in the CBF. PMID- 11761091 TI - Intra-operative quality assessment of coronary artery bypass grafts. AB - Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery. PMID- 11761092 TI - Haemolysis during cardiopulmonary bypass: how to reduce the free haemoglobin by managing the suctioned blood separately. AB - During cardiopulmonary bypass (CPB) the collection of the patient's blood from the operating area is of fundamental importance. This blood is collected in the cardiotomy reservoir using field suckers and can be managed in different ways. It can be filtered in the cardiotomy reservoir and redirected to the venous reservoir, then oxygenated and returned to the patient, or it can be managed separately: collected in the cardiotomy reservoir, treated at the end of the operation and only after this, returned to the patient. The aim of this study is to determine in vivo the effect of a separate management of the suction blood from the operative field, using the Avant D903 oxygenator (Dideco, Mirandola, Italy). Twenty-one patients undergoing coronary artery bypass graft surgery with CPB were selected and put into two groups at random. In the control group (n = 10) the suction blood in the cardiotomy reservoir was filtered and immediately redirected into the venous reservoir, oxygenated and returned to the patient. In the study group (n = 11) the suctioned blood was collected in the D903 Avant's (Dideco) cardiotomy reservoir and returned to the patient only after having been washed at the end of the operation, using a Compact Advanced (Dideco), as required. Clinical data demonstrated that while in the study group it was possible to keep the free plasma haemoglobin (FPH) concentrations the same as at the beginning, in the control group there was a significant increase in FPH from 5.0 +/- 3.5 mg/dl (baseline) to 37 +/- 16.7mg/dl (120min after CPB). PMID- 11761093 TI - Respiratory failure caused by tuberculous pneumonia requiring extracorporeal membrane oxygenation. AB - While a common pathogen, Mycobacterium tuberculosis (TB) pneumonitis is only rarely reported as a cause for respiratory failure in developed countries. We report an adolescent with TB pneumonitis and respiratory failure requiring extracorporeal membrane oxygenation (ECMO) with eventual survival. With the incidence of TB rising globally, TB should be suspected and treated as early as possible. ECMO should be considered as a treatment option if conventional ventilatory support is inadequate. ECMO survival with TB pneumonia and anti-TB antimicrobial therapy is possible. PMID- 11761094 TI - PH strategy for deep hypothermic circulatory arrest in adults. PMID- 11761095 TI - Separation of carrier-free 181Re produced in 16O-irradiated thulium target. AB - Heavy ion activation of natural Tm2O3 with 90 MeV 16O beam results in the formation of carrier-free short-lived 181Ir and 181Os which ultimately decay out to 181Re in the matrix. The liquid cation exchanger, HDEHP, has effectively been utilized as an extractant for quantitative separation of bulk thulium target matrix from carrier-free rhenium radionuclide. PMID- 11761096 TI - Recovery of 18F from [18O] water by electrochemical method. AB - An electrochemical method for producing 18F sources for the slow positron beam was applied to the recovery of 18F from H2(18)O water. The 18F of activities 150 227 mCi (5.55-8.40 GBq) was electro-deposited on a graphite rod and then emitted into pure water. The best result of the efficiency for the electro-deposition for 5 min was 97% and that for the electro-emission for 5 min was 89%. The H2(18)O water is expected to be reused much more easily by this method than by the ion exchange resin method. The metal impurities contained in the 18F solution were considerably reduced by using this method. PMID- 11761097 TI - Monte Carlo simulation of a clinical linear accelerator. AB - The effects of the physical parameters of an electron beam from a Siemens PRIMUS clinical linear accelerator (linac) on the dose distribution in water were investigated by Monte Carlo simulation. The EGS4 user code, OMEGA/BEAM, was used in this study. Various incident electron beams, for example, with different energies, spot sizes and distances from the point source, were simulated using the detailed linac head structure in the 6 MV photon mode. Approximately 10 million particles were collected in the scored plane, which was set under the reticle to form the so-called phase space file. The phase space file served as a source for simulating the dose distribution in water using DOSXYZ. Dose profiles at Dmax (1.5 cm) and PDD curves were calculated following simulating about 1 billion histories for dose profiles and 500 million histories for percent depth dose (PDD) curves in a 30 x 30 x 30 cm3 water phantom. The simulation results were compared with the data measured by a CEA film and an ion chamber. The results show that the dose profiles are influenced by the energy and the spot size, while PDD curves are primarily influenced by the energy of the incident beam. The effect of the distance from the point source on the dose profile is not significant and is recommended to be set at infinity. We also recommend adjusting the beam energy by using PDD curves and, then, adjusting the spot size by using the dose profile to maintain the consistency of the Monte Carlo results and measured data. PMID- 11761098 TI - The feasibility of accelerator-based in vivo neutron activation analysis of nitrogen. AB - The feasibility of accelerator-based in vivo neutron activation analysis of nitrogen has been investigated. It was found that a moderated neutron flux from approximately 10 microA of 2.5 MeV protons on a 9Be target performed as well as, and possibly slightly better than the existing isotope-based approach in terms of net counts per unit subject dose. Such a system may be an attractive alternative to the widespread use of (238,239)Pu/Be or 252Cf neutron sources, since there is more flexibility in the energy spectrum generated by accelerator-based neutron sources. From a radiation safety standpoint, accelerators have the advantage in that they only produce radiation when in operation. Furthermore, an accelerator beam can be pulsed, to reduce background detected in the prompt-gamma measurement, and such a device has a wide range of additional biological and medical applications. PMID- 11761099 TI - A discretized approach to determining TG-43 brachytherapy dosimetry parameters: case study using Monte Carlo calculations for the MED3633 103Pd source. AB - It is of interest to discern the energy-dependence of American Association of Physicists in Medicine (AAPM) TG-43 brachytherapy dosimetry parameters. Using Monte Carlo calculation geometry and techniques (MCNP), dependence of these parameters was calculated as a function of photon energy, in general, and for the MED3633 103Pd source using a discretized approach. Results were weighted and summed to determine the total contribution for comparison with the 103Pd source literature. Comprehensive 2-D results are discussed, and the level of agreement with other assessments are presented. PMID- 11761100 TI - An automated synthesis module for preparation of L-3-[123I]iodo-alpha-methyl tyrosine. AB - L-3-[123I]iodo-alpha-methyl tyrosine (IMT) is an artificial amino acid suitable for SPECT imaging of various tumours. Manual synthesis of this radiopharmaceutical is reliable, but time-consuming and may require handling of large quantities of radioactivity. We developed an automated IMT synthesis module, which prepares a ready-to-inject product that meets radiopharmaceutical requirements and is identical to the manually synthesised equivalent. Current advantages include decreased operator assistance time and reduced radiation exposure. Application may be extended to other radiopharmaceuticals, including high-dose preparations for therapeutic use. PMID- 11761101 TI - Modified synthesis of 11-[14C]-clozapine. AB - The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[14C] 5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%. PMID- 11761102 TI - Geometrical rectification for images from a mobile large container inspection system. AB - The mobile large container inspection system (MLCIS) is a more flexible X-ray radiographic system than conventional fixed systems. Ideally, the X-ray detectors should be arranged along an arc with the source at the center. However, detectors of the MLCIS are arranged in an L-shaped frame and result in a factual image which is distorted compared with the ideal image. We propose a geometrical rectification algorithm to convert the factual image to the ideal image. We choose the dimension ratios of identical objects shown on the factual and processed images with our algorithm as a measure, and the results is desirable. PMID- 11761103 TI - How to calculate lead concentration and concentration uncertainty in XRF in vivo bone lead analysis. AB - The authors provide a substantial correction for calculating estimates of lead concentration and uncertainty for in vivo X-ray fluorescent bone analysis with Cd 109 source. Based on general principles, they provide mathematical techniques for propagation of uncertainties in XRF analysis. They give additional considerations for lowering the detection limit and improving spectral data quality. PMID- 11761104 TI - Genetic effects induced by neutrons in Drosophila melanogaster I. Determination of absorbed dose. AB - A method to obtain the absorbed dose in Drosophila melanogaster irradiated in the thermal column facility of the Triga Mark III Reactor has been developed. The method is based on the measurements of neutron activation of gold foils produced by neutron capture to obtain the neutron fluxes. These fluxes, combined with the calculations of kinetic energy released per unit mass, enables one to obtain the absorbed doses in Drosophila melanogaster. PMID- 11761105 TI - Dosimetric characterization of a newly designed encapsulated interstitial brachytherapy source of iodine-125-model LS-1 BrachySeed. AB - A newly designed encapsulated 125I source has been introduced (Model LS-1 BrachySeed manufactured by DRAXIMAGE Inc.) for interstitial brachytherapy. In this source 125I radionuclide is contained in two ceramic beads positioned at each end of a titanium capsule. The source contains a rod of Pt-Ir, which serves as a radiographic marker for source localization in the patient. Principle photon emissions are 27.4 and 31.0 keV X-rays and a 35.5 keV gamma-ray. The 22.2 and 25.5 keV silver X-rays produced by fluorescence of the silver dopant in the ceramic bead radioisotope carriers, are also emitted. In this work, the dosimetric characteristics of the 125I source were measured with micro LiF TLD chips and dosimetry parameters were characterized based upon the American Association of Physicists in Medicine, Task Group, No. 43 formalism. The corrected 1999 National Institute of Standards and Technology standard for low energy interstitial brachytherapy sources was used to specify the air kerma strength of the sources used in this study. The dose rate constant of the sources was determined to be 1.02+/-0.07 cGy h(-1) U(-1). The radial dose function was measured and was found to be similar to that of the silver-based model 6711 125I source. However, the anisotropy function of the Model LS-1 BrachySeed source is considerably better than that of model 6711 125I source, especially on the points along and close to the longitudinal axis of the source. The BrachySeed model LS-1 provides more isotropic angular dose distribution in tissue than model 6711 125I source. The anisotropy constant for the model LS-1 source was determined to be 1.006, which is considerably better than the value of 0.93 for the model 6711 source. PMID- 11761106 TI - Nuclide-dependent local and collector surface effects in sampling of radioactive deposition to ground. AB - After the end of atmospheric nuclear weapons tests and after the Chernobyl accident, the deposition characteristics of 137Cs changed from a predominant wet deposition to the present resuspension mechanism characterised by predominant dry deposition. To study the consequences of this change for deposition sampling, monthly deposition data from two collectors located at a distance of 600 m were compared from 1991 to 2000. On the average, the deposition rates differed by roughly a factor of two for 137Cs, whereas for the cosmogenic 7Be a difference was not detectable with statistical significance. Further, a "funnel" collector with a mostly dry surface collected on the long-term average 36% less of 137Cs, but 8% less of 7Be, than a "pot" collector with a continuously water-covered surface. Since for 137Cs deposition and the bulk deposition a similar behaviour was found, a stronger sensitivity of other resuspension-derived radionuclides against local and collector surface variations can generally be expected. PMID- 11761107 TI - A theoretical model for calculation of the detective quantum efficiency in granular scintillators. AB - A theoretical model has been developed for calculating the detective quantum efficiency (DQE) of scintillators, by taking into account the internal structure of granular scintillators often used in medical imaging detectors. Scintillators were considered to consist of N elementary thin layers containing spherical scintillating grains of equal size. Grains were assumed to be regularly distributed within each thin layer, the thickness of the latter being equal to the grain diameter. Values of the X-ray absorption and X-ray attenuation coefficients, of the intrinsic X-ray to light conversion efficiency and of the optical scattering and absorption coefficients were used as input data to the model. Optical scattering and optical absorption coefficients were determined by fitting the model to experimental luminescence data. The model was employed to calculate the detective quantum efficiency of La2O2S:Tb, Y2O2S:Tb, Y2O2S:Eu, ZnSCdS:Ag, ZnSCdS:Au,Cu scintillators. Results of the calculations were found close to values published in previous studies. PMID- 11761108 TI - Possibility of using porcelain samples of high-voltage line insulators for radiation dose reconstruction by EPR spectroscopy. AB - In electron paramagnetic resonance spectra of irradiated porcelain samples from high-voltage supply line insulators three overlapping single signals were observed. The dependencies of the amplitude of these signals on the microwave power, irradiation dose and the stability in darkness and in natural light were investigated. It was concluded that for dosimetric purposes it is reasonable to use the radiation-induced signal with g = 2.001, which could be ascribed to the E' centres of quartz. The microwave power dependence of the amplitude of this signal is saturated at 1 mW, the dose dependence is saturated at about 60 mGy. A minimal level of dose determination is about 1 Gy, and it is limited mainly by the accuracy of subtraction of the background signal existing in the unirradiated sample. The radiation-induced signal is stable in the darkness, but rapidly faded in natural light, therefore, for dosimetric purposes it is possible to use only insulators covered with dark glaze or ceramic samples from the very interior of the insulators. PMID- 11761109 TI - Factor of merit and minimum detectable activity for 90Sr determinations by gas flow proportional counting or Cherenkov counting. AB - The determination of 90Sr in environmental samples can be done by using a gas flow proportional counter (beta-counting) or a liquid-scintillation spectrometer (Cherenkov counting). In this work, we present the factor of merit (FOM) and the minimum detectable activity (MDA) for both the counters. Quantitative relationships are proposed for FOM and MDA determination. PMID- 11761110 TI - Measurement of radioactivity and radon exhalation rate in different kinds of marbles and granites. AB - Geological materials usually contaminated with naturally occurring radioactive materials (NORM) have become a focus of great attention. These NORM under certain conditions can reach hazardous contamination levels. Some contamination levels may be sufficiently severe that precautions must be taken. The present study deals with 60 geological samples (marble and granite) from both Egyptian and foreign locations. The studied samples were analyzed and the concentrations in Bq/kg dry weight of radioisotopes were determined by gamma-ray spectrometry using hyper-pure germanium (HPGe) detector in Bq/kg dry weight. The absorbed dose rate due to the natural radioactivity in the samples under investigation ranged from 2.45 +/- 0.07 to 64.44 +/- 1.93 nGy/h for marble and from 41.55 +/- 1.25 to 111.94 +/- 3.36 nGy/h for granite. The radium equivalent activity varied from 5.46 +/- 0.16 to 150.52 +/- 4.52 Bq/kg for marble samples and from 229.52 +/- 6.89 to 92.16 +/- 2.76 Bq/kg for granite. The representative external hazard index values for the corresponding samples are also estimated and given. The radon exhalation rates for marble and granite samples were also calculated by using solid state nuclear track detector (CR-39). The value of radium exhalation rate varied from 8.0 +/- 2.39 to 30.20 +/- 5.06 Bq/m2/d for marble and 6.89 +/- 1.72 to 25.79 +/- 4.38 Bq/m2/d for granite and the effective radium content was found to vary from 1.700 +/- 0.51 to 6.42 +/- 1.08 Bq/kg for marble and 1.29 +/- 0.32 to 5.63 +/- 0.96 Bq/kg for granite. The values of the radon exhalation rate and effective radium content are found to correspond with the values of uranium concentration measured by the HPGe detector in the corresponding sample. PMID- 11761111 TI - Uranium mineralization in the two mica granite of gabal Ribdab area, South Eastern Desert, Egypt. AB - Among the different rock units in the Gabal Ribdab area, the two-mica leucogranite and muscovite pegmatitic granite are the most favourable host rocks for uranium and thorium mineralization. The muscovite pegmatitic granite shows evidence of post-magmatic alteration, e.g. Na- and K-metasomatism, whereas the two-mica leucogranite could be regarded as being fresh. The spectrometric survey revealed the presence of three enriched zones with a maximum eU content of 140 ppm and the maximum eTh is 36 ppm. Uranophane, zippeite and becquerelite are the most abundant uranium minerals. The origin of these secondary minerals is mainly related to alteration of primary minerals by the action of oxidizing fluids, mobilization of uranium and then redeposition in other forms. Redistribution by circulating meteoric waters might have taken place. PMID- 11761112 TI - Natural radioactivity and radon exhalation rate of soil in southern Egypt. AB - The level of natural radioactivity in soil of 30 mining samples collected from six locations in southern Egypt was measured. Concentrations of radionuclides in samples were determined by gamma-ray spectrometer using HPGe detector with a specially designed shield. The obtained results of uranium and thorium series as well as potassium (K-40) are discussed. The present data were compared with data obtained from different areas in Egypt. Also, a solid state nuclear track detector SSNTD (Cr-39) was used to measure the radon concentration as well as exhalation rate for these samples. The radon concentrations were found to vary from 1.54 to 5.37 Bq/kg. The exhalation rates were found to vary from 338.81 to 1426.47 Bq/m2d. The values of the radon exhalation rate are found to correspond with the uranium concentration values measured by the germanium detector in the corresponding soil samples. PMID- 11761113 TI - Uranium-series disequilibrium dating of secondary uranium ore from the south Eastern Desert of Egypt. AB - The secondary uranium ore of Um Ara mining area, south Eastern Desert of Egypt, is composed mainly of uranophane and beta-uranophane. They occur in the oxidized zone as idiomorphic crystals filling cavities and as coatings on the fracture surfaces of the alkali-feldspar and albitized granites. The activity ratios 234U/238U and 230Th/234U of the secondary uranium ore and host rocks indicate that there were two main phases of uranium mobility in recent geological time. An earlier precipitation of uranium from solutions forming the secondary ore and a subsequent mobilization resulted in adsorption of uranium to the host granitic rocks. The 230Th/234U age of secondary uranium ore varies from (50 +/- 10) to (159 +/- 69/-45) ka whereas, the age of uranium adsorption to the rocks ranges from (18 +/- 6) to (38 +/- 5) ka. The time of secondary uranium ore precipitation can be attributed to the Saharan II pluvial period which prevailed in Egypt during humid oxygen isotope climatic stage 5. The later uranium mobility and subsequent adsorption by the rocks took place during Kubbaniyan and Nabtian pluvial periods that coincided with oxygen isotope stages 3 and 1, respectively. PMID- 11761115 TI - Comments on 'Radiation effects in dry ice: models for a peak on the Arrhenius curve'. PMID- 11761114 TI - Radon exhalation and radiometric prospecting on rocks associated with Cu-U mineralizations in the Singhbhum shear zone, Bihar. AB - The Singhbhum thrust belt is a 200 km long arcuate orogenic belt in Bihar, eastern India. The huge mineral resources, viz. copper, uranium, magnetite, apatite and molybdenite, etc., make it significant from an economic as well as a geological point of view. The belt hosts three types of mineralization: sulphides of copper and other metals, uranium oxides and apatite-magnetite. Several distinct geological episodes are responsible for the evolution of mineralization and the thrust zone itself. Extensive and reliable radiometric prospecting and assaying have been carried out by us for the past 5 years from Dhobani in the east to Turamdih in the west of the Singhbhum shear zone. The present work indicates uranium mineralization in the Pathargora-Rakha area presently being mined for copper and also within areas in the vicinity of Bhatin. Studies on radon emanation have also been undertaken in some parts of the shear zone which indicate reasonably high radon emanation of the soils and rocks studied. This suggests the need for regular monitoring and suitable controls on the mine environment (air quality) and its vicinity. Radon emanation studies coupled with gamma-ray spectrometry and the subsequent modelling of the radiometric and radon measurements will help in the application of radon as a geophysical tracer in exploration of radioactive ore bodies and in radon risk assessment as well as in delineating active and passive faults and even in petroleum exploration. PMID- 11761116 TI - Risk analysis and the law: international law, the World Trade Organization, Codex Alimentarius and national legislation. AB - This paper discusses the place of risk analysis in international trade from a US perspective, through looking at the activities of the World Trade Organization and the Codex Alimentarius Commission. After examining what the trade agreements say about risk analysis and how international bodies are advancing and using risk analysis, the paper goes on to assess how risk analysis is used at a national level. Finally, recommendations are made for strengthening international food safety initiatives. PMID- 11761117 TI - A biomarker approach to measuring human dietary exposure to certain phthalate diesters. AB - Three groups of eight volunteers were administered stable isotope-labelled phthalate diesters in a single dose and the amount of the corresponding phthalate monoesters excreted in the urine was measured. Amongst the phthalates administered were the symmetrical dibutyl-, di-2-ethyl- and diisooctyl- phthalates along with the unsymmetrical benzylbutylphthalate. The control group received no dose, the low dose group received 168-255 microg of each phthalate and the high dose group received 336 to 510 microg of each phthalate. The excreted phthalate monoesters were measured by LC-MS following hydrolysis of conjugates. The bulk of phthalate monoester was excreted in the first 24 hour period following the dose. For dibutylphthalate, 64% and 73% on a mole basis of the low, and high dose respectively was excreted as monobutylphthalate. For dioctylphthalate (sum of the 2-ethylhexyl and the isooctyl species) the yield was 14 and 12% of the low and high dose excreted as monooctylphthalate. For benzylbutylphthalate, 67% and 78% was eliminated as monobenzylphthalate and only 6% (measured for the high dose only) was eliminated as monobutylphthalate. These conversion factors can be used in future studies to assess exposure to phthalate esters via measuring urinary levels of the monoester metabolites. PMID- 11761118 TI - Urinary biomarkers for assessing dietary exposure to caffeine. AB - The feasibility of using metabolites specific to caffeine as urinary biomarkers to be employed in the estimation of dietary caffeine intake is reported. The influence of inter-individual differences in the metabolism of caffeine and the effect of volunteer phenotype on the interpretation of potential biomarkers has been investigated using urinary caffeine metabolite data. This method of phenotype determination accurately reflected the rate constant for the cytochrome P4501A2 (CYP1A2)-catalysed 3-demethylation of caffeine in vivo. Three studies with up to 20 human volunteers demonstrated that a 24-h urine collection after a caffeine dose allows quantification of the metabolites excreted; that the ratios of selected metabolites used to classify the volunteers into fast, intermediate or slow caffeine metabolizers by CYP1A2 phenotype gave a similar result (2:7:3, slow:intermediate:fast) to that found in the general population (1:7:2); and that three metabolites, 1,7-dimethylxanthine, 1,7-dimethyluric acid and 1 methylxanthine, could be studied further as potential biomarkers for caffeine dietary intake. PMID- 11761119 TI - Assessment of dietary exposure to ochratoxin A in the UK using a duplicate diet approach and analysis of urine and plasma samples. AB - The approach to assess exposure to ochratoxin A from the diet by the analysis of human plasma and urine samples has been developed. Composite duplicate diet samples from 50 individuals and corresponding plasma and urine samples were obtained over 30 days. Samples were analysed using sensitive methods capable of measuring ochratoxin A at 0.001 ng g(-1) in food, 0.1 ng ml(-1) in plasma and 0.01 ng ml(-1) in urine. Analysis of the foods indicated ochratoxin A levels contributing to an average intake in the range 0.26-3.54 ng kg(-1) bw day(-1) over the 30 days. Ochratoxin A was found in all plasma samples and in 46 urine samples. The correlation between the plasma ochratoxin A levels and ochratoxin A consumption was not significant (95% confidence limit). However, a significant correlation was found between ochratoxin A consumption and the urine ochratoxin A concentration expressed as the total amount excreted. This new work offers the possibility of using ochratoxin A in urine as a simple and reliable biomarker to estimate exposure to this mycotoxin. PMID- 11761120 TI - Studies made to assess risk concerning a 'dioxin' contamination incident near Bolsover, Derbyshire, UK. AB - During 1990 and 1991, milk samples were collected from farms in Derbyshire, a county in the UK, as part of a study designed to establish background concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in cows' milk produced in the area. The concentrations found in two samples, both taken from farms near the town of Bolsover, were significantly elevated (40.0-42.0 ng TEQ kg(-1) fat) when compared with the normal range for these compounds in milk from the surrounding area (1.1-7.1 ng TEQ kg(-1) fat). An immediate intensive programme commenced in April 1991 to test milk from a further 27 dairy farms close to those where the original 'high' samples were obtained. A maximum tolerable concentration (MTC) was calculated to be 17.5 ng/TEQ kg(-1) fat. This was derived by using the tolerable daily intake (TDI) for 2,3,7,8-TCDD of 0.01 ng kg(-1) body weight day(-1) set by the World Health Organization in 1990 and accepted by the UK government (this figure has since been revised to 1-4 pg kg( 1) body weight day(-1)). MTC is defined as the amount of PCDD/Fs that could be present and still ensure that high-level (97.5 pecentile) consumers of milk would not exceed the TDI. Milk originating from dairies supplied by these farms and others contained PCDD/F in the range 1.8-3.1 ng TEQ kg(-1) fat, which indicated there was no risk to health for consumers purchasing milk in the normal manner. Milk from the two dairy farms was removed from the food supply until concentrations of PCDD/Fs were consistently below the MTC. The UK Department of Health monitored the blood concentrations of PCDD/Fs in individuals who had consumed milk produced on the affected farms and the Department of the Environment initiated a programme of work to identify and reduce the source of pollution. PMID- 11761121 TI - Food allergy--towards predictive testing for novel foods. AB - The risks associated with IgE-mediated food allergy highlight the need for methods to screen for potential food allergens. Clinical and immunological tests are available for the diagnosis of food allergy to known food allergens, but this does not extend to the evaluation, or prediction of allergenicity in novel foods. This category, includes foods produced using novel processes genetically modified (GM) foods, and foods that might be used as alternatives to traditional foods. Through the collation and analysis of the protein sequences of known allergens and their epitopes, it is possible to identify related groups which correlate with observed clinical cross-reactivities. 3-D modelling extends the use of sequence data and can be used to display eptiopes on the surface of a molecule. Experimental models support sequence analysis and 3-D modelling. Observed cross reactivities can be examined by Western blots prepared from native 2-D gels of a whole food preparation (e.g. hazelnut, peanut), and common proteins identified. IgEs to novel proteins can be raised in Brown Norway rat (a high IgE responder strain) and the proteins tested in simulated digest to determine epitope stability. Using the CSL serum bank, epitope binding can be examined through the ability of an allergen to cross-link the high affinity IgE receptor and thereby release mediators using in vitro cell-based models. This range of methods, in combination with data mining, provides a variety of screening options for testing the potential of a novel food to be allergenic, which does not involve prior exposure to the consumer. PMID- 11761122 TI - Food-borne Listeria monocytogenes risk assessment. AB - Listeria monocytogenes is ubiquitous in the environment and in food processing plants. Consequently, foods are frequently contaminated. However, the occurrence rate of listeriosis is only about five cases per million people per year. Listeriosis primarily strikes immunocompromised individuals, pregnant women and the elderly with a fatality rate of 20-25%. The FDA is in the process of finishing a risk assessment that is being conducted as an initial step in reviewing its approach to maximizing the public protection from foodborne L. monocytogenes. The risk assessment evaluated the presence and quantitative levels of L. monocytogenes in 21 groups of ready-to-eat foods. The potential growth of L. monocytogenes between retail point-of-sale, where contamination data originated, and consumption was modelled. The frequency and amount of consumption of these foods completed the data for the exposure assessment. For the hazard characterization or dose response part of the risk assessment, data from animal studies, virulence assays and epidemiological investigations were used to estimate the likelihood of illness for different human groups from consuming different numbers of L. monocytogenes. This risk assessment is a virtual review of current scientific knowledge. Quantitative modelling provides greater insight than a qualitative review and also indicates the uncertainty about our knowledge. The risk assessment does not attempt to define an acceptable or tolerable level of L. monocytogenes consumption or propose changes in regulations. These decisions are the responsibility of risk managers who consider additional factors such as food preferences, technical feasibility and societal values when evaluating regulatory policies. PMID- 11761123 TI - Implications of multiple antimicrobial-resistant enterococci associated with the poultry environment. AB - Poultry are increasingly being associated with carriage of multiresistant organisms that may cause disease in humans. Among these organisms are the enterococci, not regarded as a common cause of hospital-acquired infections. The use of antimicrobials for growth promotion in poultry production envronments may facilitate the dissemination of resistance to Enterococcus spp. that have the potential to be clinically significant. To assess descriptively the degree of multiresistant enterococci in the poultry environment of the Delmarva (Delaware Maryland-Virginia) East Coast region of the USA, litter samples from regional commercial poultry houses and transport container swabs from processing facilities were cultured for Enterococcus spp. Using a microtiter plate adaptation of a conventional biochemical screen, the predominant species identfied were E. faecalis (61.2%), E. faecium (18.6%) and E. gallinarum (2.4%). Resistance to the cephalosporin, macrolide and tetracycline classes of antimicrobials was uniform with broader resistance to penicillin and derivatives present in a majority of E. faecium isolates. High-level streptomycin resistance was evident in close to 30% of all isolates with a majority of E. faecalis variants possessing resistance. High-level gentamicin resistance was detected at a low frequency (2.6%) only within the E. faecalis group with resistance to low level gentamicin levels present in a majority of both the E. faecalis group and subsets of E. faecium. No unexpected vancomycin resistance was detected. Of particular interest was resistance to the streptogramin quinupristin-dalfopristin (Q-D or Synercid), which was present in 70.4% of E. faecium and E. faecium variants. PMID- 11761124 TI - Assessing the risks of pesticide residues to consumers: recent and future developments. AB - Assessing exposure of consumers to pesticide residues is an area of regulatory science that has rapidly developed over the last decade. From simplistic, deterministic models calculating lifetime exposure for adults only, assessment procedures have diversified so that more realistic estimates of long term exposures for adults, schoolchildren, toddlers and infants and short term exposures for adults and toddlers (who generally bound the more extreme consumer patterns) are now carried out. The final assessment of risk still remains a simplistic numeric comparison against hazard assessment based on a wide range of toxicity studies incorporating the appropriate safety or uncertainty factors. As development of risk assessments continues, the use of probabilistic models is becoming an invaluable information tool for quantitative risk management and aiding assessment of cumulative exposure. This paper examines the recent developments in risk assessment and consumer perception of the risks of pesticide residues, and speculates where the future developments in these areas may lie. PMID- 11761125 TI - Risk communication--the perceptions and realities. AB - This paper defines risk communication and puts it into the perspective of risk analysis as a whole. Case studies originating for the food industry are described in the areas of food colours, pesticides and genetically, modified foods to exemplify both the difficulties of risk communication and the lessons that can be learned. This paper concludes by suggesting ways in which successful risk communication should be managed. PMID- 11761126 TI - Contribution of European research to risk analysis. AB - The European Commission's, Quality of Life Research Programme, Key Action 1 Health, Food & Nutrition is mission-oriented and aims, amongst other things, at providing a healthy, safe and high-quality food supply leading to reinforced consumer confidence in the safety, of European food. Its objectives also include the enhancing of the competitiveness of the European food supply. Key Action 1 is currently supporting a number of different types of European collaborative projects in the area of risk analysis. The objectives of these projects range from the development and validation of prevention strategies including the reduction of consumers risks; development and validation of new modelling approaches, harmonization of risk assessment principles methodologies and terminology; standardization of methods and systems used for the safety evaluation of transgenic food; providing of tools for the evaluation of human viral contamination of shellfish and quality control; new methodologies for assessing the potential of unintended effects of genetically modified (genetically modified) foods; development of a risk assessment model for Cryptosporidium parvum related to the food and water industries, to the development of a communication platform for genetically modified organism, producers, retailers, regulatory authorities and consumer groups to improve safety assessment procedures, risk management strategies and risk communication; development and validation of new methods for safety testing of transgenic food; evaluation of the safety and efficacy of iron supplementation in pregnant women, evaluation of the potential cancer-preventing activity of pro- and pre-biotic ('synbiotic') combinations in human volunteers. An overview of these projects is presented here. PMID- 11761127 TI - Adjustments to managed health care: pushing against it, going with it, and making the best of it. AB - In this qualitative study of managed health care and occupational therapy practice, participants described how their practice had changed, suggested that students be educated to communicate the value of occupational therapy and to navigate corporate medicine, and expressed ethical concerns regarding reimbursement versus therapy goals. In-person, individual, focused interviews were conducted with 25 therapists in the southeastern Atlantic states. Participants' perceptions ofpervasive changes in practice due to managed health care reflected three themes of meaning: the "pushing against it" personal professional struggle; the "going with it" businesslike perspective, and the "making the best of it" optimistic outlook. These findings provide insight into therapists' occupational adaptation to managed health care. PMID- 11761128 TI - Untangling occupation and activity. AB - Activity and occupation are two core concepts of occupational therapy that are in need of differentiation. Occupation is defined here as a person's personally constructed, one-time experience within a unique context. Activity is defined as a more general, culturally shared idea about a category of action. The ways in which subjectivity and context are handled within the concepts of occupation and activity are keys to disentangling them. The proposed untangling of the two concepts into distinct definitions is congruent with their historical origins as well as with current definitional trends. Once occupation and activity are recognized as two separate and equally valuable concepts, they offer a rich set of theoretical relations for exploration. The clarity that will result from differentiating occupation and activity will enhance disciplinary discourse and research as well as enhance the intervention efficacy, moral surety, and political strength of the profession. PMID- 11761129 TI - Beyond the unobtrusive observer: reflections on researcher-informant relationships in urban ethnography. AB - Ethnographic research involves the creation and ongoing renegotiations of relationships between researchers and informants. Prolonged engagement contributes to the complexity as relationships deepen and shift over time and participants accumulate a substantial reservoir of shared experiences. Reflections about the relationships we have co-constructed with informants in several research projects have contributed to our identification of several critical aspects of building and maintaining researcher-informant relationships in cross-cultural research. Aspects of relationship work specifically related to conducting ethnography with children, within the communities in which researchers live, and within the practice of occupational therapy are discussed. PMID- 11761130 TI - Effect of interactive metronome training on children with ADHD. AB - OBJECTIVE: The purpose of this study was to determine the effects of a specific intervention, the Interactive Metronome, on selected aspects of motor and cognitive skills in a group of children with attention deficit hyperactivity disorder (ADHD). METHOD: The study included 56 boys who were 6years to 12 years of age and diagnosed before they entered the study as having ADHD. The participants were pretested and randomly assigned to one of three matched groups. A group of 19 participants receiving 15 hr of Interactive Metronome training exercises were compared with a group receiving no intervention and a group receiving training on selected computer video games. RESULTS: A significant pattern of improvement across 53 of 58 variables favoring the Interactive Metronome treatment was found. Additionally, several significant differences were found among the treatment groups and between pretreatment and posttreatment factors on performance in areas of attention, motor control, language processing, reading, and parental reports of improvements in regulation of aggressive behavior. CONCLUSION: The Interactive Metronome training appears to facilitate a number of capacities, including attention, motor control, and selected academic skills, in boys with ADHD. PMID- 11761131 TI - Theoretical and clinical perspectives on the Interactive Metronome: a view from occupational therapy practice. PMID- 11761132 TI - From waiting to relating: parents' experiences in the waiting room of an occupational therapy clinic. AB - OBJECTIVE: The purpose of this study was to gain an understanding ofparents'perceptions of outcomes of occupational therapy intervention using a sensory integration approach. METHOD: Interviews with parents regarding their childrens participation in occupational therapy were analyzed using grounded theory. RESULTS: The parents' experiences of sitting in the waiting room while their children received occupational therapy emerged as a powerful outcome theme. Through their interactions with other parents, this particular group of parents gave and received naturally occurring support for parenting children with sensory integrative dysfunction. Additionally, by virtue of repeated experiences of waiting, parents moved to positions of liminality, shared weekly rituals, engaged in downward social comparison, and reframed their views of their children. CONCLUSION: Implications are proposedfor expanding the definition of family centered intervention; attending to the meaning of the cultural world of practice; and directing future research related to how a physical setting, such as a waiting room, might shape naturally occurring support and social interaction. PMID- 11761133 TI - Pencil grasp and children's handwriting legibility during different-length writing tasks. AB - OBJECTIVE: This study examined the influence ofpencil grasp on handwriting legibility during both short and long writing tasks in 46fourth-grade students who were typically developing. Matched samples were used to controlfor variability. METHOD: Regular classroom writing assignments were scoredfor word and letter legibility, and scores were compared using a mixed repeated-measures analysis of variance design. The two independent variables were pencil grasp (dynamic tripod grasp vs. atypical grasp) and task length (short vs. long). RESULTS: A significant difference was found between the letter legibility scores on the short task and the letter legibility scores on the long task. Students' legibility was greater on the short task than on the long task across both grasp conditions. No significant difference was found in scores between students who used dynamic tripod grasps and those who used atypical grasps, nor was there a significant interaction between grasp and task length. No significant differences were found between word legibility scores. CONCLUSION: The results indicate that although the students in this study wrote more legibly on the short task than on the long task, the type of grasp they used did not affect their legibility. Because of the limited sample size, the results of this study should be interpreted cautiously. More research in handwriting performance and pencil grasp is needed to provide clear expectations and treatment options for students. PMID- 11761134 TI - Validity of the baltimore therapeutic equipment work simulator in the measurement of lifting endurance in healthy men. AB - OBJECTIVE: To examine the criterion validity of the Baltimore Therapeutic Equipment (BTE) work simulator by comparing endurance time, oxygen uptake (VO2), and heart rate measured during real and simulated lifting tasks and to derive a regression equation for predicting actual lifting endurance from measurements on the work simulator. METHOD: Twenty healthy male volunteers repetitively lifted and lowered a load of 40 lb using the BTE work simulator and actual weights at a laboratory workstation. Postures, location, and frequency of lifts were kept constant. Endurance (defined as the time taken for the rating of perceived exertion to increase 2 units on the Borg scale) was measured under both conditions. VO2 and heart rate were also recorded, using standard physiological procedures. RESULTS: The mean values for endurance time, steady-state VO2, and heart rate were significantly different between the real and simulated tasks (p < .05). Correlation of endurance time between the two tasks was significant (r = .71, p < .05). Step wise regression analysis resulted in the following equation for predicting real endurance from simulated time measurements: predicted real time = .34 simulated time + 3.29; r = .71; SE = 1.00 min. CONCLUSION: The BTE work simulator tends to overestimate real lifting endurance performance in healthy men. The lower physiological stress during the simulated task suggests a significant difference between the real and simulated loads. Occupational therapists should exercise caution when using the results of the BTE work simulator during functional capacity evaluations. PMID- 11761135 TI - "Tears in my eyes 'cause somebody finally understood": client perceptions of practitioners following brain injury. AB - OBJECTIVE: The purpose of this study was to identify practitioner qualities and traits that clients with brain injury see as important. METHOD: An opportunistic sample of 51 participants with brain injury was interviewed about perceptions of service access and effectiveness. An interview guide was used to gather data for this phenomenological qualitative study. Four interviewers individually conducted audiotaped interviews, which were then transcribed. Coding and theme development were completed using HyperRESEARCH software. RESULTS: Three themes regarding practitioner qualities emerged from the data: (a) roles of the provider, (b) perceived helpfulness of services, and (c) personal characteristics of the providers. Beneficial provider roles included advocate, friend, mentor, and team member. Perceptions of helpfulness of the services included relevance, meaningfulness, practical application, skill development potential, and whether periodic feedback on progress was provided. Personal characteristics of the provider valued by the participants were clear and honest communicator, supportive, respectful, good listener, and understanding. CONCLUSIONS: Practitioners need to pay increased attention to the perceptions of care and services of clients with brain injury. The current study closely supports previous research related to quality of care in the medical and community arenas and offers some additional suggestions to professionals who work with persons with brain injury, including learning how to time giving information to clients and how to understand client concerns without being prescriptive. Future research in this area needs to focus on and describe providers who demonstrate an ability through their willingness to don a variety of roles, their helpful services, and their personal characteristics-to meet the unique needs of clients with brain injury. PMID- 11761136 TI - Increased pain tolerance as an indicator of return to work in low-back injuries after work hardening. AB - OBJECTIVE: This study examined retrospective data from a multidisciplinary work hardening program that compared patients who did and did not return to work after low-back injury. The objective of this study was to identify differences between these groups to better guide work-hardening programs and return-to-work decisions. METHOD: Retrospective data from patients with low-back injuries (n = 115) who participated in a northern California work-hardening program were analyzed. Using two-way analysis of variance, male and female patients who did and did not return to work were compared. RESULTS: No significant differences were found between men and women for any of the variables studied. Patients who did and did not return to work were not significantly different in age, length of injury, and subjective pain at the beginning or end of the work-hardening program or in activity tolerance (p = .08). Patients who returned to work perceived a significantly (p < or = . 05) greater improvement in pain tolerance by the end of the work-hardening program than those who did not return to work. CONCLUSION: The results of this study suggest that rehabilitation emphasis should not be placed on the reduction of subjective pain but, rather, on strategies to cope with existing pain while improving functional ability. PMID- 11761137 TI - A literature review of the effect of handedness on isometric grip strength differences of the left and right hands. AB - When estimating preinjury grip strengthfor compensation and rehabilitation purposes, two methods have been identified in the literature: (a) comparison with the unaffected hand and (b) reference to grip strength normative data. The literature is divided about whether a significant difference exists between the grip strengths of a person's two healthy hands. Some researchers argue that handedness affects the grip strength ratio. According to these authors, there is considerable variation in the definition of handedness, its effect on grip strength ratios, and the methods of assessing handedness as it relates to grip strength. The complexity of defining and accurately evaluating handedness is discussed in this literature review. Inappropriateness of the current use of self report questionnaires for determining handedness for grip strength purposes is highlighted. The impact of the effect of handedness on grip strength ratios cannot be clarified until a consistent definition and evaluation method for assessing handedness is developed. This handedness definition then needs to be applied to appropriately designed hand grip strength studies. PMID- 11761138 TI - Effect of wrist positioning on the repeatability and strength of power grip. AB - OBJECTIVE: This study tested the between-day repeatability and effect of wrist positioning on grip strength measurement. METHOD: Thirty healthy men 20 years to 69 years of age were tested twice, 1 week apart, in six wrist positions. RESULTS: The findings showed good repeatability for grip strength, with the intraclass correlation coefficient [ICC(1, 3)] ranging from .9043 to .9663. Significant differences were found in grip strength among the six positions (p < . 001), with grip strength measured at 15 degrees or 30 degrees of wrist extension (EXT) and 0 degrees ulnar deviation (UD) significantly greater than that of 0 degrees UD and 0 degrees EXT or 15 degrees UD with or without EXT This finding suggests the clinical importance of standardizing the testing position for grip strength measurement. CONCLUSION: The high repeatability of the tests supports the use of the grip strength measurement to evaluate treatment progress. PMID- 11761139 TI - Student attitudes toward persons with mental illness: the influence of course work and level I fieldwork. PMID- 11761141 TI - Postdoctoral training for new doctoral graduates: taking a step beyond a doctorate. PMID- 11761140 TI - Therapeutic use of humor: occupational therapy clinicians' perceptions and practices. PMID- 11761142 TI - Conference report: qualitative evidence-based practice. PMID- 11761143 TI - Research over the next century: impact of technology. PMID- 11761144 TI - The occurrence of culmorin and hydroxy-culmorins in cereals. AB - Forty-five samples from 1988-1995 of naturally contaminated grain, barley, wheat and oats, three samples of mixed feed, and 16 samples of grain artificially inoculated with Fusarium culmorum during the flowering stage were analysed for deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-acetyl-DON), culmorin and hydroxy culmorins. These compounds are secondary metabolites produced by the fungal species F. culmorum and F. graminearum. Acetonitrile-water extract of the samples was purified on a Mycosep #225 column, derivetized using penta-fluoropropionic anhydride (PFPA) and analysed by gas chromatography-mass spectrometry (GC-MS). The amount of each of culmorin, 5-, 12-, 14 and 15-hydroxy-culmorin and one unknown hydroxy-culmorin were determined relative to the amount of DON plus 3 acetyl DON for each sample. The ratio between the total amount of culmorin compounds and the DON compounds ranged from 0.14 to 1.07 in the samples. This study shows that there is a strong correlation between the amount of DON present in the grain and the amount of culmorin and hydroxy-culmorins present. The ratio of each of the culmorin compounds relative to the amount of DON compounds were in the same range in the grain artificially inoculated by F. culmorum as found in an earlier study for F. culmorum strains cultivated on rice, while the hydroxy culmorin profile in the naturally contaminated grain was more similar to what was found for the F. graminearum cultures in the same study. These results indicate that F. graminearum may be a relatively important source for DON in grain also in relatively cold areas. PMID- 11761145 TI - Studies on the molecular ecology of Blastomyces dermatitidis. AB - The microecology of Blastomyces dermatitidis, the dimorphic etiologic agent of the potentially fatal systemic fungal infection, blastomycosis, is not well defined. Blastomyces dermatitidis may occur periodically at natural sites, perhaps aided by rotting organic material, animal droppings and physical changes. Semi-quantitative growth studies of B. dermatitidis on 2% agar plates determined the ability to utilize or tolerate a variety of substrates including simple and complex molecules as carbon source, and organic and inorganic nitrogen sources. Allantoin, creatinine, quanidoacetic acid, guanidine and cysteine may be used as sole nitrogen source. Allantoin in combination with dextrose, glycerol, lichenen, celloboise and other wood by-products support growth of B. dermatitidis at room temperature. The nutritional conversion of the fungus to the yeast form at room temperature, well demonstrated on allantoin/glycerol/yeast extract media, appears to be affected by certain inorganic compounds. The organism tolerates low to moderate levels of alpha-pinene, tannic acid, shikimic acid, veratryl alcohol, vanillic acid, and polyethyleneglycol-200. There are significant differences among isolates regarding growth on various substances at 20 degrees and 37 degrees centigrade. It appears that a variety of wood by-products and animal waste substrates, in combination, support the growth of B. dermatitidis. Their role in the ecological niche of B. dermatitidis, and the importance of nutritional dimorphism in the natural environment warrants further investigation. PMID- 11761146 TI - Cell-mediated immune responses (CMIR) in human rhinosporidiosis. AB - Cell mediated immune responses (CMIR) to Rhinosporidium seeberi in human patients with rhinosporidiosis have been studied. With immuno-histochemistry, the cell infiltration patterns in rhinosporidial tissues from 7 patients were similar. The mixed cell infiltrate consisted of many plasma cells, fewer CD68+ macrophages, a population of CD3+ T lymphocytes, and CD56/57+ NK lymphocytes which were positive for CD3 as well. CD4+ T helper cells were scarce. CD8+ suppressor/cytotoxic cytolytic cells were numerous. Most of the CD8+ cells were TIA1+ and therefore of the cytotoxic subtype. CD8+ T cells were not sub-typed according to their cytokine profile; 1L2, IFN-gamma (Tcl); IL4, ILS (Tc2). In lympho-proliferative response (LPR) assays in vitro, lymphocytes from rhinosporidial patients showed stimulatory responses to Con A but lymphocytes from some patients showed significantly diminished responses to rhinosporidial extracts as compared with unstimulated cells or cells stimulated by Con A, indicating suppressor immune responses in rhinosporidiosis. The overall stimulatory responses with Con A suggested that the rhinosporidial lymphocytes were not non-specifically anergic although comparisons of depressed LPR of rhinosporidial lymphocytes from individual patients, to rhinosporidial antigen with those to Con A, did not reveal a clear indication as to whether the depression was antigen specific or non-specific. The intensity of depression of the LPR in rhinosporidial patients bore no relation to the site, duration, or the number of lesions or whether the disease was localized or disseminated. Rhinosporidial extracts showed stimulatory activity on normal control lymphocytes, perhaps indicating mitogenic activity. These results indicate that CMIR develops in human rhinosporidiosis, while suppressed responses are also induced. PMID- 11761147 TI - Cell-mediated immune responses (CMIR) to Rhinosporidium seeberi in mice. AB - There is no published data on Cell Mediated Immune Responses in experimental animals to Rhinosporidium seeberi the causative agent of human and animal rhinosporidiosis. The quantitative mouse foot-pad model was used to assay the Delayed-Type Hypersensitivity (DTH) cell-mediated immune response to extracts of purified endospores and sporangia of R. seeberi. Histological examination was used to confirm that the foot-pad reactions were compatible with DTH reactions in the mouse. We report that sonically disintegrated rhinosporidial endospores/sporangia induced DTH responses in the foot-pads of sensitized mice which were comparable in intensity and histological profile to that induced by sheep red blood cells in SRBC sensitized mice. Anti-rhinosporidial antibody was also induced. Filtrates of the soluble antigens in sonicated suspensions failed to evoke a DTH-foot-pad (DTH-FP) response in sensitized mice although an anti rhinosporidial antibody response to this preparation was detected. Prolonged pre treatment with sonicated suspensions of endospores and sporangia resulted in a decrease of DTH reactivity as compared with reactions following pre-treatment of a shorter duration. PMID- 11761148 TI - Human hair colonizing fungi in water sediments of India. AB - Out of 144 samples of water sediments, 183 isolates belonging to 9 genera and 22 species were isolated. Fifty-nine isolates of Acremonium, 26 of Chrysosporium indicum, 22 of Chrysosporium keratinophilum, 17 of Malbranchea sp. and 10 of Microsporum gypseum were recovered. Acremonium implicatum, Chrysosporium georgii, Chrysosporium xerophilum and Geomyces pannorum were reported for the first time from India. PMID- 11761149 TI - Genetic and physiological variants of yeast selected from palm wine. AB - Genetic screening of 1200-palm wine yeasts lead to the selection of fourteen isolates with various genetic and physiological properties. Nine of the isolates were identified as Saccharamyces species, three as Candida species, one as Schizosaccharomyces species and one as Kluyveromyces species. Five of the isolates were wild type parents, two were respiratory deficient mutants (rho) and nine were auxotrophic mutants. Four isolates were heterozygous diploid (alphaa) and two were homozygous diploid (aa/alphaalpha) for the mating a mating types were further identified on mating with type loci. Four Mat alpha and four Mat a types were further identified on mating with standard haploid yeast strains. Forty-five percent sporulated on starvation medium producing tetrads. Fifty-two percent of the four-spored asci contained four viable spores. Maximum specific growth rate [micromax] of the fourteen isolates range from 0.13-0.26, five isolates were able to utilize exogenous nitrate for growth. Percentage alcohol production range between 5.8-8.8% for palm wine yeast, 8.5% for bakers' yeast and 10.4% for brewers yeast. The palm wine yeast were more tolerant to exogenous alcohol but had a low alcohol productivity. Hybridization enhanced alcohol productivity and tolerance in the palm wine yeasts. PMID- 11761150 TI - Rapid method for the determination of ochratoxin A in urine by immunoaffinity column clean-up and high-performance liquid chromatography. AB - A rapid and accurate method to quantify ochratoxin A (OTA) at ppt (pg/ml) levels in urine has been developed. The method uses commercial immunoaffinity columns for clean-up and reversed phase high-performance liquid chromatography (HPLC) with fluorescence detector for quantification of the toxin. Average recoveries of OTA from human urine spiked at levels from 0.05 ng/ml to 1.0 ng/ml ranged from 88% to 93%, with relative standard deviations (RSDs) between 1% and 8%. Detection limit was 0.005 ng/ml. Out of 41 human urine samples, 25 were found positive to OTA with only one sample exceeding 0.05 ng/ml; the latter originated from a patient affected by karyomegalic interstitial nephritis. The method can be used as a rapid and non-invasive tool to assess human and animal exposure to OTA in epidemiological studies and to establish the possible role of OTA in acute animal intoxications or human end-stage renal diseases. PMID- 11761151 TI - Toxic activity from liquid culture of Colletotrichum acutatum. AB - Colletotrichum acutatum has become an increasingly important plant pathogen worldwide. With this background, a study was carried out to characterize the toxicity of liquid culture media from different isolates and to identify some properties of the toxic principles. Liquid culture media from all isolates were toxic to rubber leaves and induced the anthracnose symptoms. Toxicity of the culture filtrate was not host specific and toxic substances were thermostable. Acetone soluble fraction of the culture filtrates retained the toxic activity and it was effective even at a concentration of 700 microg dry mycelium mass/ml. PMID- 11761152 TI - The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides. AB - Developed over the past two decades, the antisense strategy has become a technology of recognised therapeutic potential, and many of the problems raised earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cells remains an important and inordinately difficult challenge. Synthetic polymers appeared on this scene in the middle 1980s, and there is a surprisingly large variety used or proposed so far as agents for delivery of oligodeoxynucleotides. After discussing the principles of antisense strategy, certain aspects of the ingestion of macromolecules by cells, and the present situation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and or cell membrane permeabilisation agents for delivery of antisense oligodeoxynucleotides. Structural aspects of various polymers, as well as the results, promises and limitations of their use are critically evaluated. PMID- 11761153 TI - Preparation of oxidized glucose-crosslinked N-alkylated chitosan membrane and in vitro studies of pH-sensitive drug delivery behaviour. AB - Glucose was oxidized to generate a glucose dialdehyde and chitosan (CS) was hydrophobicallly modified with butyl bromide, octyl bromide and dexyl bromide. The analysis of IR and X-ray diffraction results of CS derivatives confirms that the hydrogen bonds and crystallinity were weakened by the incorporation of pendant alkyl. The permeability coefficient P and diffusion coefficient D for model drug vitamin B2 through oxidized glucose-crosslinked alkylated CS membrane were determined under different pH media. The results show that for the same alkylated CS in different pH media, P and D decrease with an increase in pH; for different alkxylated CSs in acidic media, P and D diminish with the increase in the length of alkyl side, which is supposedly originated from the enhancement of hydrophobicity. In alkali medium, P and D show a rising trend with the increase in the length of alkyl chain, which might be related to the loose stacking of network as it occurs to shrink in alkali medium. The preliminary cytotoxicity assay indicates that oxidized glucose-crosslinked alkylate CS membrane is non toxic in vitro. PMID- 11761154 TI - Mechanical and in vitro testing of aerosol-gel deposited titania coatings for biocompatible applications. AB - The biocompatible properties of sol-gel litania have increased the interest in the mechanical properties of this material in the form of functional coatings for prosthetic applications. In the present work. titania coatings with thicknesses of 1 microm have been prepared using the aerosol gel process. The main objective has been to evaluate the mechanical properties of the coatings and to prove their in-vitro biocompatibility. For this purpose, the hardness and Young's modulus of the coatings were measured by nanoindentation with loads in the 6-30 mN range. A continuous increase of these magnitudes was observed for the coatings treated at increasing sintering temperatures (150-800 degrees C). The hardness and the Young's modulus ranged between 15.8-19.5 GPa and 142-186 GPa, respectively. This behaviour has been confirmed by measurements of the plastic energy of deformation in 10 mN full loading unloading tests and by determination of the mean indentation creep under 30 mN loads. The films were additionally characterised by XRD. FTIR and ellipsometry to study the chemical and structural changes produced by sintering. Biocompatibility tests are very conclusive. Cells seeded on aerosol gel titania coatings grow while adhered onto the surface. These coatings are thus of potential interest for the enhancement of the properties of prosthetic TiAlV alloys. PMID- 11761155 TI - The role of protein adsorption on chondrocyte adhesion to a heterocyclic methacrylate polymer system. AB - Chondrocyte adhesion to a polymer system consisting of poly(ethyl methacrylate) and tetrahydrofurfuryl methacrylate (PEMA/THFMA) has been investigated in vitro. The adhesive glycoproteins, fibronectin and vitronectin were studied for their role in promoting cell attachment. Fibronectin was the best substrate for chondrocyte attachment, if it was pre-adsorbed and did not have to compete with other proteins for attachment sites. Chondrocytes began to spread on fibronectin coated glass although they remained rounded on the libronectin coated PEMA/THFMA system. Vitronectin was better at competing with the other proteins in serum and was the main adhesive protein for chondrocyte attachment to TCP and the PEMA/THFMA system in normal serum medium. Serum contains non-adhesive proteins that compete for binding sites and hence reduce cell attachment. The alpha5beta1 and alpha(v)beta3/beta5 integrins were detected on the chondrocytes although there may be a difference in expression between different material surfaces. PMID- 11761156 TI - Cancellous bone repair using bovine trabecular bone matrix particulates. AB - At 5 and 15 weeks post-surgery, biomechanical and histological analyses of cancellous bone defects filled with the bovine trabecular bone matrix (BBM) and hydroxyapatite (Hap) particulates of dimensions 106-150 microm were investigated. It was observed that at 5 weeks post-surgery the stiffness properties of the BBM filled defects were significantly higher than those observed in the Hap filled defects (p < 0.01) but comparable to those recorded in intact cancellous bone from the same anatomical position. Histologically, no significant differences were observed in the percentage of new bone contact with the particles. The biomechanical properties of the Hap filled defects mirrored those in intact cancellous bone only at 15 weeks post-surgery. BBM particles thus appeared to accelerate the early healing of osteotomies. It is therefore suggested that particles of this bioceramic be the subject of intense research for more usage in both periodontal osseous defects and orthopaedic fractures. PMID- 11761157 TI - Effects of Si speciation on the in vitro bioactivity of glasses. AB - The surface reactivity of glasses belonging to the (mol%) 31SiO2-11P2O5-(58-x)CaO xMgO series, with x ranging from 0 to 32, was studied in Kokubo's simulated body fluid (SBF). Scanning electron microscopy, inductively coupled plasma spectroscopy and Fourier transform infrared spectroscopy were used to characterise the glass surface and the SBF compositional changes. All glasses develop surface layers rich in silica and calcium phosphate. An increasing surface activity with increasing MgO/CaO ratio was observed. In a previous investigation using magic-angle spinning nuclear magnetic resonance it was found that there is an increasing abundance of Q0 species in the glass structure with increasing MgO content. The present work shows that, when immersed in SBF, Q0 rich glasses are easily leached to form a silica gel layer. It is concluded that MgO in the glass indirectly improves the early stages of mineralisation by favouring Q0 speciation. This mechanism plays an important role in glass bioactivity. PMID- 11761158 TI - Conformation of a model peptide of the tandem repeat decapeptide in mussel adhesive protein by NMR and MD simulations. AB - The conformation of a model peptide (Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys) of the tandem repeat decapeptide sequence of Mytilus edulis foot protein-1 (mefp-1) has been studied by 1H and 13C 2D-NMR in three diverse media-DMSO-d6, water (pH 3.5) and 40% hexafluoroacetone (HFA). Various NMR parameters that were used to deduce the secondary structure were chemical shift (1H and 13C) temperature coefficients of NH chemical shifts, 3J(NH alpha) coupling constants and the pattern of intra and inter-residue NOEs. Molecular dynamics simulations making integral use of the NMR data shows that the conformation of the peptide is conserved in all the three media. The structure in the three solvents is best defined as a left-handed polyproline II helix (PPII). PMID- 11761159 TI - Three-dimensional reconstruction of confocal laser microscopy images to study the behaviour of osteoblastic cells grown on biomaterials. AB - The adhesion, spreading and cytoskeletal organization of osteoblastic cells seeded onto titanium and titania/hydroxyapatite composite coating (TiO2/HA) were studied using images acquired by confocal laser scanning microscopy. The fluorescence staining technique was employed to visualize actin cytoskeletal organization of cells, 2-D images were exhaustive when the cells were seeded at low density (in the first 24 h of incubation), but they were less clear when the cells proliferated and appeared stacked. Since the shareware software were not satisfactory, a new 3-D image reconstruction was developed using ordinary software and a model was obtained directly from the optical section set, in order to achieve a more realistic and faithful vision of morphological structures and to evaluate the behaviour of bone cells grown on materials. The results showed that the cells grown on titanium conform to the irregular substrate surfaces maximizing the contact between the cell membrane and the substrate and proliferate disposing close to each other. On the contrary, the osteoblasts seeded onto TiO2/HA coating develop clusters where the cells aggregated extending processes in order to establish intercellular connections. Cell aggregation is an early and critical event leading to cell differentiation and mineralization process and could be a first signal of the tendency of TiO2/HA coating to stimulate cell differentiation. PMID- 11761160 TI - Ectopic osteogenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits. AB - Porous calcium phosphate ceramics consisting of hydroxyapatite (HA) and tricalcium phosphate (TCP) with different HA to TCP ratio were implanted intramuscularly in rabbits for six months in order to carry out a comparative study on osteogenic activity of the ceramics. Bone formation was detected only in HT73 (HA to TCP ratio, 7-3) specimens. Other implants, HT28 (2-8) and HT010 (0 10), could not induce bone. After a six-month period of implantation, HT28 and HT010 implants showed obvious degradation of the implants changing their shape and size macro and microscopically. Microscopically, they showed aggregates of fine particles and appearance of multinucleated cells. However, HT73 implants was less degraded and could maintain their original structure macro and microscopically. This study showed that HT73 ceramics can induce bone in rabbit muscle tissue and it is considered that maintenance of porous structure, that is, degradation rate of the materials may be one of the affecting factors in ceramic induced osteogenesis. PMID- 11761161 TI - Organization of cyclic AMP-dependent connexin 43 in Swiss 3T3 cells attached to a cellulose substratum. AB - We have previously shown that the adenylyl cyclase, which produces cyclic AMP (cAMP) in Swiss 3T3 cells, is activated by their attachment to a cellulose substratum (Cuprophan, CU). This substratum adsorbs vitronectin poorly, prevents cell spreading and causes them to aggregate. By contrast, cells spread out on polystyrene and contain low concentrations of cAMP. We have found that Connexin 43 (Cx 43) gap junction plaques are involved in this cell aggregation. MDL 12330 A, a specific inhibitor of adenylyl cyclase, prevented cell aggregation on CU and abolished Cx 43 channel clustering. But forskolin, a direct activator of adenylyl cyclase, and SBr cAMP, a cell-permeable analogue of cAMP, caused Cx 43 channel clustering in cells attached to polystyrene. Hence, Cx 43 channel clustering is regulated by cAMP in Swiss 3T3 cells. In addition, neither brefeldin A nor monensin (inhibitors of transit through the endoplasmic reticulum and Golgi apparatus), abolished Cx 43 channel clustering in cells aggregated on CU. Thus, the Cx 43 that form clusters in cells attached to CU are not dependent upon the trafficking of Cx 43 from intracellular storage sites, but are probably reorganised from the plasma membrane. PMID- 11761162 TI - Fabrication of Zn containing apatite cement and its initial evaluation using human osteoblastic cells. AB - Recently, the effects of Zn2+ on osteogenesis stimulation have become major topics in the research fields of bone formation and organism essential elements. Based on the fundamental finding of Zn2+ with respect to osteogenesis stimulation, Ito et al. have prepared Zn doped beta-tricalcium phosphate (ZnTCP) and have reported that ZnTCP enhances the proliferation of MC3T3-E1 cells. In this investigation, we studied the effects of ZnTCP added to apatite cement (AC) with respect to its setting reaction and proliferation of human osteoblastic cells as an initial evaluation for the feasibility of AC containing ZnTCP. Compositional analysis using powder X-ray diffractometer revealed that ZnTCP shows no reactivity with the setting reaction of AC. As a result, the mechanical strength of set AC decreased increasing amounts of added ZnTCP as if ZnTCP acts as a pore in AC. The setting time of AC was not affected by addition of ZnTCP up to 10%. When AC containing ZnTCP was immersed in alpha-MEM containing 10% bovine serum, Zn2+ was released from AC. Larger amounts of Zn2+ were released from AC containing larger amounts of ZnTCP. When human osteoblastic cells were incubated on the surface of AC discs, proliferation of human osteoblastic cells was significantly increased on the surface of AC that contained 5% ZnTCP when compared with that containing no ZnTCP. In contrast, proliferation of human osteoblastic cells decreased on the surface of AC that contained 10% ZnTCP when compared with that free from ZnTCP; indicating cytotoxicity. We concluded therefore, that addition of ZnTCP to AC is useful to enhance the osteoconductivity of AC when release of Zn2+ can be carefully regulated. PMID- 11761163 TI - Hemocompatibility of heparin-coated surfaces and the role of selective plasma protein adsorption. AB - Although several studies have shown that heparin-coated surfaces reduce the activation of both the complement system and the coagulation system, there is still inadequate understanding of the factors initiating and controlling blood activation at these surfaces. We investigated the adsorption profile of 12 common plasma proteins (and the platelet receptor CD41) to a heparin coating (Carmeda BioActive surface (CBAS)) compared to uncoated controls (PVC) by using an in vitro whole blood Chandler-Loop model. Surface bound proteins were studied kinetically by a direct ELISA technique. Western blots were performed on the SDS eluates in order to detect adsorbed cleavage products and denatured proteins. Changes in plasma levels of neutrophil activation markers, platelet activation, coagulation activation, complement activation and the inflammatory response were measured by conventional ELISAs. This study showed significant differences in adsorption patterns among the heparin-coated and the uncoated surfaces, notably for fibronectin, fibrinogen, C3 and high molecular weight kininogen (HMWK). The kinetic studies confirmed the results obtained from Western blots and indicated specific adsorption profiles of plasma proteins. We assume that at least some of the improved blood compatibility of the heparin-coated surfaces may be ascribed to the selective uptake and cleavage of plasma proteins. PMID- 11761164 TI - Protein-containing hydrophobic coatings and films. AB - The incorporation of enzymes and other proteins into hydrophobic polymeric coatings and films has been investigated in this study with the goal of generating biologically active materials for biocatalysis, antifouling surfaces, and biorecognition. The protein-polymer composites are created using standard solution coating techniques with poly(methyl methacrylate), polystyrene, and poly(vinyl acetate) as polymers and alpha-chymotrypsin and trypsin as biocatalysts. The specific enzyme is first extracted into a nonpolar organic solvent using hydrophobic ion-pairing. The ion-paired enzyme is dried and redissolved into a solvent also miscible with the polymer. This solution is then poured over a surface and the solvent is allowed to evaporate to form the enzyme containing coating, which can then be delaminated to form a film. Leaching of enzyme from and activity of the biocatalytic coatings and films were evaluated. The biocatalytic coatings showed no loss of activity over ca. one week. For the biocatalytic films, the leaching rate was initially high followed by a slow rate of enzyme loss. Activity was measurable for at least one month, with only ca. one third of the initial activity lost in that time, while, being continuously incubated in a buffer solution. Activity was also exhibited on macromolecular (protein) substrates. The biocatalytic coatings could be reused over 100 times with only a modest loss of activity. Finally, coatings and films containing a lectin (Concanavalin A) were capable of selectively binding to glycoproteins, thereby extending the application of such films for use in bioseparations and biorecognition. PMID- 11761165 TI - Biocompatibility of anionic collagen matrix as scaffold for bone healing. AB - The basic approach to the treatment of bone defects involves the use of scaffolds to favor tissue growth. Although several bioscaffolds have been proposed for this purpose, the search for new and enhanced materials continues in an attempt to address the drawbacks of the present ones. Modifying current materials can be a fast and cheap way to develop new ones. Among them, type I collagen allows its structure to be modified using relatively simple techniques. By means of an alkaline treatment, anionic collagen with enhanced piezoelectric properties can be obtained through hydrolysis of carboxyamides groups of asparagine and glutamine residues from collagen in carboxylic. The process applied to a raw source of collagen, bovine pericardium, provided a sponge-like structure, with heterogeneous pore size, and, moreover, the complete removal of interstitial cells. For the evaluation of the biocompatibility of such matrices, they were implanted in surgically created bone defects in rat tibias. Empty defects served as controls. This experimental model allowed a preliminary evaluation of the osteoconductiveness of the matrices. The histological results presented a low inflammatory response and bone formation within a short period of time, similar to that of controls. The low cost of production associated to the biocompatibility and osteoconductivity performance make the anionic collagen matrices promising alternatives for bone defects treatment. PMID- 11761166 TI - Preparation of controlled release ophthalmic drops, for glaucoma therapy using thermosensitive poly-N-isopropylacrylamide. AB - In this study, controlled release ophthalmic agents for glaucoma therapy were developed based on the thermosensitivity of poly-N-isopropylacrylamide (PNIPAAm). The clear solution of PNIPAAm was known to undergo phase transition when the temperature was raised from the room temperature to about 32 degrees C. The drug was entrapped in the tangled polymer chains or encapsulated within the crosslinked polymer hydrogel at room temperature, and released progressively after topical application (i.e., at a higher temperature). Linear PNIPAAm and crosslinked PNIAAm nanoparticles containing epinephrine were prepared. The drug release rate and cytotoxicity were investigated in vitro. Ophthalmic formulations based on either linear PNIPAAm or the mixture of linear PNIPAAm and crosslinked PNIPAAm nanoparticles were administered to rabbits and the intraocular pressure (IOP)-lowering effect was evaluated. The decreased pressure response of the formulation based on linear PNIPAAm lasted six-fold longer than that of the conventional eye drop. Furthermore, for formulation based on the mixture of linear PNIPAAm and crosslinked nanoparticles, the pressure-lowering effect lasted eight times longer. These results suggest the use of thermosensitive polymer solutions or hydrogels is potential in controlled release antiglaucoma ophthalmic drugs. PMID- 11761167 TI - In vitro response of macrophages to a new carbon-polylactide composite for the treatment of periodontal diseases. AB - The purpose of the study was to examine the response of macrophages and the concentration of selected released cytokines following contact with a new carbon polylactide composite. The macrophages were grown on samples of the materials and on each of its components separately. Viability of the cells as well as concentrations of interleukins IL-6, IL-10, IL-12 and TNF-alpha were then determined. Some differences in the viability of the cells were demonstrated. They varied according to the kind of material used. After incubation with the serum, the composite and its components induced the release of IL-6, IL-12 and TNF-alpha which did not differ significantly from one another. PMID- 11761168 TI - Galactosylated alginate as a scaffold for hepatocytes entrapment. AB - Galactose moieties were covalently coupled with alginate through ethylenediamine as the spacer for enhancing the interaction of hepatocytes with alginate. Adhesion of hepatocytes onto the galactosylated alginate (GA)-coated polystyrene (PS) surface showed an 18-fold increase as compared with that of the alginate coated surface and it increased with an increase in the concentration of GA. The morphologies of attached hepatocytes were observed to spread out at the 0.15 wt% GA-coated PS surface while round cells were observed at the 0.5 wt% GA-coated PS surface. Inhibition of hepatocytes attachment onto the galactose-carrying PS coated surface occurred with the addition of the GA into the hepatocyte suspension, indicating the binding of GA with hepatocytes via the patch of asialoglycoprotein receptors. Primary hepatocytes were entrapped in the GA/Ca2+ capsules (GAC). Higher cell viability and more spheroid formation of hepatocytes were obtained in the GAC than in the alginate/Ca2+ capsules (AC). Moreover, liver functions of the hepatocytes such as albumin secretion and urea synthesis in the GAC were improved in comparison with those in the AC. PMID- 11761169 TI - Interaction of glucuronic acid and iduronic acid-rich glycosaminoglycans and their modified forms with hydroxyapatite. AB - Proteoglycans and their spatial arms, glycosaminoglycans (GAGs), are known to interact with hydroxyapatite (HAP) and have been implicated as important modulators of mineralisation. In the present study isotherm data (0.02 M sodium acetate, pH 6.8) revealed that the iduronic-rich GAGs heparan sulphate, heparin and dermatan sulphate showed greater binding onto HAP with higher adsorption maxima compared with the glucuronic acid-rich GAGs chondroitin-4-sulphate, chondroitin-6-sulphate and hyaluronan. Chemically desulphated chondroitin showed no adsorption onto HAP. With the exception of hyaluronan, the GAGs studied showed no desorbability in sodium acetate buffer only, whereas in di-sodium orthophosphate, desorption occurred much more readily. The data indicates that GAG chemistry and conformation in solution greatly influence the interaction of these molecules with HAP. The conformational flexibility of iduronic acid residues may be an important determinant in the strong binding of iduronic acid rich GAGs to HAP, increasing the possibility of the appended anionic groups matching calcium sites on the HAP surface, compared with more rigid glucuronic acid residues. This work provides important information concerning interfacial adsorption phenomena between the organic-inorganic phases of mineralised systems. PMID- 11761170 TI - Characteristics of the surface oxides on turned and electrochemically oxidized pure titanium implants up to dielectric breakdown: the oxide thickness, micropore configurations, surface roughness, crystal structure and chemical composition. AB - Titanium implants have been used widely and successfully for various types of bone-anchored reconstructions. It is believed that properties of oxide films covering titanium implant surfaces are of crucial importance for a successful osseointegration, in particular at compromized bone sites. The aim of the present study is to investigate the surface properties of anodic oxides formed on commercially pure (c.p.) titanium screw implants as well as to study 'native' oxides on turned c.p. titanium implants. Anodic oxides were prepared by galvanostatic mode in CH3COOH up to the high forming voltage of dielectric breakdown and spark formation. The oxide thicknesses, measured with Auger electron spectroscopy (AES), were in the range of about 200-1000 nm. Barrier and porous structures dominated the surface morphology of the anodic film. Quantitative morphometric analyses of the micropore structures were performed using an image analysis system on scanning electron microscopy (SEM) negatives. The pore sizes were < or = 8 microm in diameter and had 1.27-2.1 microm2 opening area. The porosity was in the range of 12.7-24.4%. The surface roughness was in the range of 0.96-1.03 microm (Sa), measured with TopScan 3D. The crystal structures of the titanium oxide were amorphous, anatase, and a mixtures of anatase and rutile type, as analyzed with thin-film X-ray diffractometry (TF-XRD) and Raman spectroscopy. The chemical compositions consisted mainly of TiO2, characterized with X-ray photoelectron spectroscopy (XPS). The native (thermal) oxide on turned implants was 17.4 nm (+/- 6.2) thick and amorphous. Its chemical composition was TiO2. The surface roughness had an average height deviation of 0.83 microm (Sa). The present results are needed to elucidate the influence of the oxide properties on the biological reaction. The results of animal studies using the presently characterized surface oxides on titanium implants will be published separately. PMID- 11761171 TI - A synthetic aragonite-based bioceramic: influence of process parameters on porosity and compressive strength. AB - We investigate the influence of process parameters such as weight fraction and particle size of pore-former, and isostatic pressure, on porosity and compressive strength of non-sintered porous calcium carbonate biomaterials compacted at high pressure in uniaxial or isostatic mode. Experiment design and results analysis are performed according to a two-level 2k factorial design method (FDM). Results indicate that only the weight fraction of pore-former (wt fpf) influences significantly the porosity and the compressive strength. The porosity P, is described by a linear function of wt fpf, and the compressive strength sigma(comp), by an exponential one. For materials compacted under uniaxial pressing: P (vol%) = 33.7 + 85.4 (wt fpf) and sigma(comp) (MPa) = 28.8e(-9.2(wt fpf)) with 0.1 < or = wt fpf < or = 0.3. For materials compacted in isostatic mode: P (vol%) = 33.9 + 82.1 (wt fpf) and sigma(comp) (MPa) = 24.0e(-7.0(wt fpf)) with 0.15 < or = wt fpf < or = 0.35. The pore-former particle size has no significant influence on both properties. The increase in isostatic pressure provides slightly lower porosity and better compressive strength. For a fixed fraction of pore-former, isostatic pressing leads to a better compressive strength than uniaxial pressing. This study indicates that, for a constant amount of pore former, the size of macropores can be adjusted to reach optimal bone ingrowth without change in compressive strength. PMID- 11761172 TI - Selective adhesion of astrocytes to surfaces modified with immobilized peptides. AB - Under serum-free conditions, rat skin fibroblasts, but not cortical astrocytes, selectively adhered to glass surfaces modified with the integrin-ligand peptide RGDS. In contrast, astrocytes, but not fibroblasts, exhibited enhanced adhesion onto substrates modified with KHIFSDDSSE, a peptide that mimics a homophilic binding domain of neural cell adhesion molecule (NCAM). Astrocyte and fibroblast adhesion onto substrates modified with the integrin ligands IKVAV and YIGSR as well as the control peptides RDGS and SEDSDKFISH were similar to that observed on aminophase glass (reference substrate). This study is the first to demonstrate the use of immobilized KHIFSDDSSE in selectively modulating astrocyte and fibroblast adhesion on material surfaces, potentially leading to materials that promote specific functions of cells involved in the response(s) of central nervous system tissues to injury. This information could be incorporated into novel biomaterials designed to improve the long-term performance of the next generation of neural prostheses. PMID- 11761173 TI - Inflammatory responses to orthopaedic biomaterials in the murine air pouch. AB - An in vivo model of the inflammatory response to orthopaedic biomaterials was used to examine cellular and cytokine responses to polymer particles of ultra high molecular weight polyethylene (UHMWPE) and polymethylmethacrylate (PMMA), and metal particles of cobalt-chrome (Co-Cr) and titanium alloy (Ti-6Al-4V). Responses were determined separately and in combinations, to examine interactions between different forms of biomaterials. Murine air pouches were injected with particle suspensions, and reactions evaluated using histological, immunological, and molecular techniques. All particulate biomaterials caused significant increases in membrane thickness compared with control (saline) air pouches, with the highest reaction seen in response to Ti-6Al-4V particles. A synergistic increase in membrane thickness was observed when PMMA was combined with UHMWPE, suggesting that multiple biomaterial stimuli markedly increase the inflammatory reaction. Cellular analysis indicated that all particles increased the absolute number and the percentage of macrophages in the membrane over the control level, with the most pronounced increase due to individual biomaterial occurring with UHMWPE particles. Cytokine analysis revealed that biomaterials provoked a strong IL-1 response. Ti-6Al-4V stimulated the highest IL-6 gene transcription and the lowest IL-1 gene transcription. The data suggest that synergism in the inflammatory response to biomaterials may be important in adverse responses to orthopaedic wear debris. PMID- 11761174 TI - New hydrogel matrices containing an anti-inflammatory agent. Evaluation of in vitro release and photoprotective activity. AB - In the present work. the preparation and characterization of hydrogels based on alpha,beta-polyaspartylhydrazide (PAHy) chemically crosslinked with ethyleneglycol diglycidylether (EGDGE) containing Tolmetin sodium salt, are reported. In particular, these samples have been prepared both as water swellable microparticles and as gels at two different crosslinking degrees. The incorporation of Tolmetin sodium salt in PAHy-EGDGE microparticles has been performed after the crosslinking reaction by a soaking procedure or during the formation of the network. The influence of drug loading procedure on Tolmetin release has been evaluated by performing in vitro release study in simulated gastrointestinal fluids (pH 1.0/6.8) using the pH variation method and in phosphate buffered saline, pH 7.4. PAHy-EGDGE networks containing Tolmetin sodium salt have been also prepared as gels. These have showed a slowed down release as evidenced by in vitro release studies at pH 5.0 and 7.4 using a Franz diffusion cell system and an artificial membrane. Finally, PAHy EGDGE networks provide a pronounced reduction of the photosensitizing activity of Tolmetin, as evidenced by in vitro hemolysis assays. PMID- 11761175 TI - Tissue engineered microsphere-based matrices for bone repair: design and evaluation. AB - The need for synthetic alternatives to conventional bone grafts is due to the limitations of current grafting materials. Our approach has been to design polymer-based graft substitutes using microsphere technology. The gel microsphere matrix and the sintered microsphere matrix were designed using the random packing of poly(lactide-co-glycolide) microspheres to create a three-dimensional porous structure. The evaluation of these methods dealt with analysis of effects of matrix composition and processing. Matrices were evaluated structurally by scanning electron microscopy and porosimetry, and biomechanically by compression testing. The evaluation revealed the high modulus of the gel microsphere matrix and the versatility of the sintered microsphere matrix. The gel microsphere matrix incorporated hydroxyapatite particles and had a Young's modulus of 1651 MPa, but structural analysis through SEM revealed a pore system less optimal for bone in-growth. The sintered microsphere matrices were fabricated without hydroxyapatite particles by thermally fusing polymeric microspheres into a three dimensional array, possessing interconnectivity and a modulus range of 241 (+/ 82)-349 (+/-89) MPa. The sintered microsphere matrix demonstrated a connected pore system and mechanical properties in the mid-range of cancellous bone. Porosimetry data indicated that matrix pore diameter varied directly with microsphere diameter, while pore volume was independent of microsphere diameter in the range of diameters examined. The microsphere-based matrices show promise as polymeric substitutes for bone repair. PMID- 11761176 TI - Thermally responsive polymer-grafted surfaces facilitate patterned cell seeding and co-culture. AB - Tissue engineering constructs that effectively duplicate natural tissue function must also maintain tissue architectural and organization features, particularly the integration of multiple cell types preserving distinct, integrated phenotypes. Cell-cell communication and biochemical cross-talk have been shown to be essential for the maintenance of differentiated cell functions in tissues and organs. Current limitations of cell-culture hinder progress in understanding the features and dynamics of heterotypic cell communication pathways critical to developing more sophisticated or effective tissue-engineered devices. We describe a method to conveniently electron-beam pattern cell culture surfaces with thermo responsive polymer chemistry that exploits changes in cell-polymer adhesive interactions over a temperature window amenable for high-throughput cell culture. Cells seeded on these patterned surfaces at 20 degrees C adhere only to surface areas lacking thermo-responsive grafting chemistry; grafted domains at 20 degrees C are hydrophilic and non-cell adhesive. The culture temperature is then increased to 37 degrees C collapsing the hydrated grafted chemistry. A second cell type is added to the culture and adheres only to these exposed relatively hydrophobic grafted patterns. Both cell types can then be effectively co-cultured at 37 degrees C under multiple conditions. Long-term cell pattern fidelity and differentiated cell functions characteristic of each co-planar cell type are observed. This method is simple and has few limitations, compared with other existing co-culture methods. PMID- 11761177 TI - Increasing hydroxyapatite incorporation into poly(methylmethacrylate) cement increases osteoblast adhesion and response. AB - Poly(methylmethacrylate) (PMMA) is the current standard for cement held prostheses. It forms a strong bond with the implant, but the bond between the cement and the bone is considered to be weak, with fibroblastic cells observed at the implant site, rather than direct bone contact, a contributing factor leading to implant failure. Incorporation of hydroxyapatite (HA) increases the biological response to the cement from tissue around the implant site, thus giving increased bone apposition. In this study, PMMA discs with 0, 4.6 and 8.8 vol%. HA were examined. Primary human osteoblast-like cells (HOBs) were used for the biological evaluation of the response to the cements in vitro. Morphology was observed using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Measurement of tritiated thymidine (3H-TdR) incorporation and alkaline phosphatase (ALP) activity were used to assess proliferation and differentiation. A synergy between increasing focal contact formation, cytoskeletal organisation, cell proliferation and expression of phenotype was observed with increasing HA volume. Preferential anchorage of HOBs to HA rather than PMMA was a prominent observation. PMID- 11761178 TI - Biomaterial patches sutured onto the rat stomach induce a set of genes encoding pancreatic enzymes. AB - Asymmetric patches of polyhydroxybutyric acid with one smooth and one rough surface were produced by a dipping procedure. These patches were implanted into the rat gastrointestine and tissue samples were generated at distinct time intervals after surgery. The host's response towards the foreign material was analyzed by Differential Display and RNA profiles were compared to each other. One to two weeks after surgery a group of mRNAs encoding pancreatic enzymes was transiently present after biomaterial implantation. PMID- 11761179 TI - Function of linear and cyclic RGD-containing peptides in osteoprogenitor cells adhesion process. AB - Cell adhesion directly influences cell growth, differentiation and migration as well as morphogenesis, integrity and repair. The extracellular matrix (ECM) elaborated by osteoblast cells constitutes a regulator of the cell adhesion process and then of the related phenomenon. These regulatory effects of ECM are mediated through integrins and some of them are able to bind RGD sequences. The aim of this study was to determine the role of the sequence and the structure of RGD-containing peptides (linear and cyclic) as well as their role in the cell adhesion process. Cell adhesion assays onto ECM proteins coated surfaces were performed using a range of linear and cyclic RGD-containing peptides. We showed a different human osteoprogenitor cell adhesion according to the coating for ECM proteins and for RGD-peptides. Inhibition assays using peptides showed different responses depending on the coated protein. Depending on the amino-acid sequence and the structure of the peptides (cyclic linear), we observed 100% inhibition of cell adhesion onto vitronectin. These results suggest the importance of sequence, structure and conformation of the peptide, which may play a crucial function in the ligand/receptor interaction and/or in the stability of the interaction. PMID- 11761180 TI - Biological performance of calcium phosphate films formed on commercially pure Ti by electron-beam evaporation. AB - Thin and defect-free calcium phosphate films with a Ca/P ratio of 1.62 were formed by electron-beam evaporation. The as-deposited films had average bonding strengths to the metal implants of 64.8 MPa and the dissolution rates of 47.5 nm/h in isotonic saline solutions. The interface mechanical characteristics and histology of the as-machined, as-blasted, and calcium phosphate coating on the machined surfaces of commercially pure titanium were investigated. After a healing period of 12 weeks, the implants were unscrewed with a torque gauge instrument at the day of sacrifice. The coated sample showed a removal torque of 48.5 Ncm (SD 5.4) compared to 32.3 Ncm (SD 2.91) for the uncoated implant with the same surface roughness, and 47.3 Ncm (SD 5.8) for the grit blasted screw. The histomorphometric analyses of the calcium-phosphate-coated implants revealed a mean of 52.4% (SD 6.3) as the highest bone to implant contact. PMID- 11761181 TI - In vitro testing of the potential for orthopedic bone cements to cause apoptosis of osteoblast-like cells. AB - The purpose of this study was to investigate in vitro the apoptosis- and/or necrosis-inducing potential of polymethylmethacrylate (PMMA)-based bone cements for prosthetic surgery. Four bone cements widely used in orthopedics were tested as extracts onto osteoblast-like MG-63 cells and for comparison, HL-60 cells, which are remarkably sensitive to apoptotic stimuli. Neutral red uptake (NRU) was used to measure cell viability while Hoechst 33258 staining was used to detect DNA content. Apoptosis was characterized using a BrdU-based ELISA assay for DNA fragmentation and examined by fluorescence microscopy using acridine orange and propidium iodide staining of nuclei. The generation of reactive oxygen species (ROS), which could mediate apoptosis, was verified using dichlorofluorescein diacetate (DCFH-DA) oxidation to DCF. After 24 h of challenge of the cells with the four cement extracts, the viability of either MG-63 or HL-60 cells was found to be unaltered, as recorded by NRU. Apoptotic cell death was induced by three cements in HL-60, whereas MG-63 cells were significantly affected by the four cements tested: the finding of DNA fragments both in the cytoplasm and supernatants of MG-63 after 24 h demonstrated that these cells underwent late apoptosis secondary necrosis. Fluorescent staining of the nuclei confirmed the results obtained with the ELISA test. Oxygen free radicals were elicited by two cements in HL-60 cells, while MG-63 did not generate ROS in response to cements. This study helps to gain more insight into the mechanism of cell death induced by PMMA-based cements and suggests apoptosis of osteoblasts as a part of the tissue reaction around cemented prostheses. PMID- 11761182 TI - Use of coupling agents to enhance the interfacial interactions in starch EVOH/hydroxylapatite composites. AB - Different zirconate, titanate and silane coupling agents were selected in an effort to improve the mechanical properties of starch and ethylene-vinyl alcohol copolymer (EVOH) hydroxylapatite (HA) composites, through the enhancement of the filler particles-polymer matrix interactions and the promotion of the interfacial adhesion between these two phases. The mechanical performance was assessed by tensile tests and discussed on the basis of the respective interfacial morphology (evaluated by scanning electron microscopy). The main relevant parameters were found to be the surface properties and reactivity of the filler (non-sintered HA) and the chemical nature (pH and type of metallic centre) of the added coupling agent. Significant improvements in the stiffness were achieved (about 30% increase in the modulus) when using the acidic zirconate coupling agents. The acidic zirconate combined the capability of crosslinking the polymer matrix with the establishment of donor-acceptor interactions and hydrogen bonding between it and the ceramic particles, leading to very good interfacial adhesion. The optimization of these coupling processes associated with the introduction of higher amounts of filler, may be an effective way to produce composites with mechanical properties analogous to those of the human cortical bone. PMID- 11761183 TI - Plague virulence. PMID- 11761184 TI - Hetero-resistance: an under-recognised confounder in diagnosis and therapy? PMID- 11761185 TI - Detection of Helicobacter pylori in faeces by culture, PCR and enzyme immunoassay. AB - Various techniques such as culture, PCR and enzyme immunoassay have been used to detect Helicobacter pylori infection in human faecal specimens. Attempts to culture H. pylori have had limited success as the bacterium exists predominantly in a non-culturable (coccoid) form in the faeces. Several PCR protocols, differing from each other in the choice of genomic targets and primers, have been used to detect H. pylori infection. Substances in faeces that inhibit PCR have been removed by various pre-PCR steps such as filtration through a polypropylene membrane, biochemical separation by column chromatography and isolation of H. pylori with immunomagnetic beads, the former two techniques yielding results with a high degree of sensitivity and specificity. An enzyme immunoassay based on the detection of H. pylori antigen in faeces has become a convenient tool for the pre treatment diagnosis of the infection. The stool antigen assay is convenient, especially for children, as it involves neither surgery nor the discomfort associated with the urea breath test. However, its applicability in monitoring eradication therapy has been controversial, as the assay can detect dead or partially degraded bacteria long after actual eradication, thus giving false positive results. PMID- 11761186 TI - Interaction of Yersinia enterocolitica and Y. pseudotuberculosis with platelets. AB - Yersinia enterocolitica is a bacterium capable of growth at 4 degrees C in donated blood and has been responsible for many deaths following transfusion. Interaction of Y. enterocolitica with blood cells is of interest in understanding the mechanisms of survival and growth in blood. The closely related organism Y. pseudotuberculosis is known to invade platelets and cause platelet aggregation by a mechanism that involves expression of the chromosomal inv gene. Yersinia isolates were made to express green fluorescent protein (GFP) and their interaction with platelets was studied by flow cytometry, enterocolitica did not cause platelet aggregation or activation, not even when grown at 22 degrees C to maximise inv expression. Attachment of Y. enterocolitica O:9 to platelets occurred with virulence plasmid-bearing (pYV+) strains grown at 37 degrees C but not with pYV- strains nor with strains grown at 22 degrees C. Y. pseudotuberculosis containing inv did cause platelet activation and aggregation when grown at 22 degrees C, as has been shown before, but also showed enhanced attachment to platelets when grown at 37 degrees C. Electron microscopy studies confirmed that inv-expressing Y. pseudotuberculosis invaded platelets but Y. enterocolitica attached only to the outer surface of platelets. Interaction of Y. enterocolitica O:9 with platelets provided a modest protection against bacterial killing by human serum. Interaction of Y. enterocolitica O:9 with platelets does not lead to platelet invasion or activation, and is mediated through plasmid coded factors, not inv. PMID- 11761187 TI - Characterisation of p-nitrophenylglycerol-resistant Proteus mirabilis super swarming mutants. AB - p-Nitrophenylglycerol (PNPG) inhibits the co-ordinately regulated activities of swarming behaviour and virulence factor expression in Proteus mirabilis. The inhibitory action of PNPG was investigated by the isolation of Tn5 insertion mutants that could swarm, albeit with much reduced ability, in the presence of PNPG. The mutants exhibited a super-swarming phenotype in the absence of PNPG; i.e., they migrated further in a given time than did the wild-type cells. Cloning and sequence analysis of the mutants indicated that Tn5 was inserted into the rsbA gene, which may encode a membrane sensor histidine kinase of the bacterial two-component signalling system. In the absence of PNPG, the mutants exhibited several swarming-related phenotypes that were different from those of the wild type; they initiated swarming earlier and had a less conspicuous consolidation phase, they differentiated earlier and maintained a differentiated state for longer, they started to express virulence factors earlier and maintained high expression levels of these factors for longer, and they had higher cell invasion ability than the wild type. These mutant phenotypes could be complemented by a plasmid-borne copy of rsbA. Together, these data suggest that RsbA may act as a repressor of swarming and virulence factor expression. In the presence of PNPG, these rsbA-mutated mutants could still swarm, differentiate and express virulence factors, whereas the wild type could not, suggesting that PNPG may target RsbA or RsbA-regulated pathways to exert its inhibitory effect. Together, these data reveal a novel mechanism through which bacteria may negatively regulate swarming differentiation and virulence factor expression and identify a potential target of PNPG action. PMID- 11761188 TI - Survival and distribution of cell-free SEF 21 of Salmonella enterica serovar Enteritidis in the stomach and various compartments of the rat gastrointestinal tract in vivo. AB - Rats were dosed for 6 days with purified SEF 21 fimbriae of Salmonella enterica serovar Enteritidis 10360. The levels of fimbriae in gut contents associated with tissues and in the faeces were quantified by direct non-competitive ELISA. SEF 21 was distributed throughout the gut. The majority was found in the large intestine where it was primarily in the luminal contents. In contrast, a high proportion of SEF 21 detected in the ileum, the main site of salmonella colonisation and invasion, was tissue-bound. Thus, purified SEF 21 survived intestinal passage and associated with the stomach and gastrointestinal tract in a pattern similar to that found with whole Salmonella cells. PMID- 11761189 TI - A portuguese isolate of Borrelia lusitaniae induces disease in C3H/HeN mice. AB - A low-passage, Portuguese isolate of Borrelia lusitaniae, strain PotiB2, was inoculated into C3H/HeN mice and disease was monitored by histopathology at 8 weeks after spirochaete challenge. Ear, heart, bladder, femoro-tibial joint, brain and spinal cord were examined. B. lusitaniae strain PotiB2 (6 of 10 mice) and B. burgdorferi sensu stricto strain N40 (9 of 10 mice) induced similar lesions in the bladder of infected mice characterised as a multifocal, lymphoid, interstitial cystitis. Moreover, both B. lusitaniae PotiB2 and B. burdorferi N40 induced lesions in the heart of infected mice. The lesions induced by B. lusitaniae PotiB2 (2 of 10 mice) were characterised as a severe, necrotising endarteritis of the aorta, with a minimal, mixed inflammatory infiltrate (neutrophils, macrophages and lymphoid cells) extending into the adjacent myocardium. In contrast, B. burgdorferi N40 induced a periarteritis of the pulmonary artery (7 of 10 mice), with no involvement of the endothelium and more extensive inflammation and subsequent necrosis of the adjacent myocardium. This infiltrate was composed entirely of mononuclear cells, predominantly mature lymphocytes and plasma cells. No lesions were noted in the joints or central nervous system with inoculation of strains N40 or PotiB2, and co-inoculation of either strain with Ixodes ricinus salivary gland lysate did not affect the resulting pathology. Serology, examined 8 weeks after inoculation, indicated a different reactivity in mice infected with B. lusitaniae PotiB2 compared with B. burgdorferi N40. Immunoblot analysis demonstrated that mice with lesions resulting from infection with B. lusitaniae PotiB2 reacted only to the flagellin protein (41 kDa) or to flagellin and OspC, whereas mice infected with B. burgdorferi N40 reacted with multiple high and low mol. wt proteins, including flagellin, p93, p39, OspA, OspB and OspC. These results indicate that B. lusitaniae PotiB2 induced pathology similar to B. burgdorferi N40 when inoculated into susceptible mice. Moreover, these results establish the first animal model of disease with B. lusitaniae. This mouse model can be used to characterise the immunopathogenesis of B. lusitaniae infection and to delineate the proteins responsible for disease induction in susceptible mice. PMID- 11761190 TI - Isolation and characterisation of a novel spirochaete from severe virulent ovine foot rot. AB - A novel spirochaete was isolated from a case of severe virulent ovine foot rot (SVOFR) by immunomagnetic separation with beads coated with polyclonal anti treponemal antisera and prolonged anaerobic broth culture. The as yet unnamed treponeme differs considerably from the only other spirochaete isolated from ovine foot rot as regards morphology, enzymic profile and 16S rDNA sequence. On the basis of 16S rDNA, it was most closely related to another unnamed spirochaete isolated from cases of bovine digital dermatitis in the USA, raising the possibility of cross-species transmission. Further information is required to establish this novel ovine spirochaete as the cause of SVOFR. PMID- 11761191 TI - Characterisation and differentiation of lactobacilli by lectin typing. AB - Lactobacillus isolates from healthy Estonian and Swedish children were characterised by a lectin typing technique; 56 isolates from six species (L. acidophilus, L. paracasei, L. plantarum, L. fermentum, L. brevis and L. buchneri) were tested. The typing system was based on an agglutination assay with a panel of six commercially available lectins, which were chosen on the basis of their carbohydrate specificities. The isolates were also subjected to proteolytic degradation before lectin typing to decrease auto-agglutination of whole cells in the assay. The 56 isolates were divided into 15 different lectin types by their lectin agglutination patterns. Proteolytic treatment reduced auto-agglutination for the majority of species, apart from L. acidophilus, which remained predominantly auto-agglutinating (eight of nine strains). The system produced stable and reproducible results under standardised culture conditions. Lactobacilli are important bacteria for use as probiotics and this system may supplement current molecular typing techniques and may help in identification of strains that could be useful in this role. PMID- 11761192 TI - Comparison of SmaI-defined genotypes of Campylobacter jejuni examined by KpnI: a population-based study. AB - Pulsed-field gel electrophoresis (PFGE) was used to analyse 147 isolates collected in two regions of Quebec province (Estrie and Montreal) between March 1998 and Feb. 1999, to determine the utility of molecular strain typing for a population-based collection of Campylobacter jejuni and to compare directly the discriminatory power of SmaI and KpnI restriction digests. With a combination of epidemiological criteria including space and time plus molecular strain typing, 49% of isolates from Estrie and 39% of isolates from Montreal were identified as belonging to a putative cluster. For 41% of the cases, sources were either missing or explicitly unknown; the remaining sources were subject to recall bias. Thus, the evaluation of sporadic cases of campylobacter enteritis by descriptive clinical investigation alone is neither sensitive nor reliable for identifying sources of infection. In the PFGE analysis, KpnI digests provided appreciably greater discriminatory power than SmaI digests. When combining the PFGE analyses with basic epidemiological criteria, 30% of the putative SmaI clusters were inconsistent with the epidemiological criteria compared with 17% of the KpnI clusters. Among the 98 isolates assigned to clusters by SmaI, only 65% gave concordant results with KpnI. In contrast, among the 81 isolates assigned to clusters by KpnI, 92% gave concordant results with SmaI. Finally, clusters that were epidemiologically related to ingestion of raw milk and specific water sources correlated better with the typing results based on KpnI than SmaI. Thus, KpnI is the enzyme of choice for molecular epidemiology studies of C. jejuni. The combination of continuous epidemiological surveillance and molecular strain typing may be useful for identifying new sources and mechanisms of transmission for community-acquired C. jejuni infection andultimately for developing new approaches to prevention. PMID- 11761193 TI - PCR ribotyping of clinically important Clostridium difficile strains from Hungary. AB - Isolates of Clostridium difficile from different hospital wards at the University Hospital of Szeged in Hungary were typed by PCR amplification of rRNA intergenic spacer regions (PCR ribotyping). A total of 15 different ribotypes was detected among the 65 isolates tested. The predominant type, PCR ribotype 087, accounted for 39% of all isolates, in contrast with an international typing study where ribotype 001 was the most common. Two non-toxigenic C. difficile strains were found to exhibit the same pattern, which was distinct from those of all the ribotypes described previously, suggesting that this is a new type. PMID- 11761194 TI - Prevalence of cytolethal distending toxin (cdt) genes and CDT production in Campylobacter spp. isolated from Danish broilers. AB - The pathogenesis of campylobacter infection in man is largely unknown, although cytolethal distending toxin (CDT) has been incriminated as a virulence factor. However, little is known about the cdt genes in Campylobacter spp. isolated from broiler chickens. A total of 350 cloacal swabs was collected and tested by conventional culture and PCR. Of the 114 Campylobacter isolates obtained, 101 (88.6%) were identified as C. jejuni and 13 (11.4%) as C. coli by conventional methods. cdt genes were detected by PCR in all the isolates except one C. jejuni isolate. Cytotoxic effects were produced in a Vero cell line, by 100 of the C. jejuni isolates. In contrast, 10 C. coli isolates produced much lower levels of toxin and 3 produced no detectable toxin. These results confirm the common occurrence of campylobacter infection in chickens and indicate that cdt genes are commonly present in both C. jejuni and C. coli isolates from broilers, but that there are distinct differences in CDT production in these two closely related species. PMID- 11761195 TI - Seasonal variations in nasopharyngeal carriage of respiratory pathogens in healthy Italian children attending day-care centres or schools. AB - The aim of this study was to investigate seasonal variations in the prevalence of the nasopharyngeal carriage of respiratory pathogens and identify factors affecting colonisation patterns in healthy children. The nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis during two seasons (autumn and spring) was evaluated in 1580 healthy children aged 1-7 years by means of a cohort study conducted in day-care centres and schools in eight Italian cities. A questionnaire was used to obtain the epidemiological data. In all, 309 children (19.5%) carried one or more respiratory pathogens in the autumn, and 375 children (23.7%) in the spring. This variation was due to H. influenzae alone or in combination (autumn: S. pneumoniae 60, 3.8%; H. influenzae 206, 13.0%, M. catarrhalis 71, 4.5%; spring: S. pneumoniae 75, 4.7%; H. influenzae 288, 18.2%, M. catarrhalis 82, 5.2%). Colonisation with two or more pathogens increased from 9.1% in the spring to 17.3% in the autumn. Seasonal variations occur in the prevalence of the nasopharyngeal carriage of respiratory pathogens in healthy children attending day-care centres or schools in Italy. However, although statistically significant, the difference was slight and had limited clinical relevance. Therefore, seasonal influence on the nasopharyngeal carriage of respiratory pathogens in healthy children was negligible. PMID- 11761196 TI - Comparison of PCR, capture ELISA and immunoblotting for detection of Toxoplasma gondii in infected mice. AB - PCR was compared with capture ELISA and immunoblotting for the detection of Toxoplasma gondii in sera of acutely infected mice. One hundred animals were inoculated intraperitoneally with 5000 trophozoites of RH strain and five of them were killed every 3 h from 3 h to 21 h post infection (p.i.), and every day from day 1 to day 7 p.i.. No assay detected the parasite from 3 h p.i. to 15 h p.i. PCR was the most sensitive assay and detected the T. gondii from 18 h p.i., whereas the other assays detected it only from day 1. PMID- 11761197 TI - Comparative performance of Fungichrom I, Candifast and API 20C Aux systems in the identification of clinically significant yeasts. AB - To compare the performance of current chromogenic yeast identification methods, three commercial systems (API 20C Aux, Fungichrom I and Candifast) were evaluated in parallel, along with conventional tests to identify yeasts commonly isolated in this clinical microbiology laboratory. In all, 116 clinical isolates, (68 Candida albicans, 12 C. parapsilosis, 12 C. glabrata and 24 other yeasts) were tested. Germ-tube production, microscopical morphology and other conventional methods were used as standards to definitively identify yeast isolates. The percentage of isolates identified correctly varied between 82.7% and 95.6%. Overall, the performance obtained with Fungichrom I was highest with 95.6% identification (111 of 116 isolates). The performance of API 20C Aux was higher with 87% (101 of 116 isolates) than that of Candifast with 82.7% (96 of 116). The Fungichrom I method was found to be rapid, as 90% of strains were identified after incubation for 24 h at 30 degrees C. Both of the chromogenic yeast identification systems provided a simple, accurate alternative to API 20C Aux and conventional assimilation methods for the rapid identification of most commonly encountered isolates of Candida spp. Fungichrom seemed to be the most appropriate system for use in a clinical microbiology laboratory, due to its good performance with regard to sensitivity, ease of use and reading, rapidity and the cost per test. PMID- 11761198 TI - MMR and the age of unreason. PMID- 11761199 TI - Ensuring patient safety. PMID- 11761200 TI - The predictive value of asthma medications to identify individuals with asthma--a study in German general practices. AB - BACKGROUND: The assessment of prescribing performance by aggregated measures mainly developed from automated databases is often helpful for general practitioners. For asthma treatment, the frequently applied ratio of anti inflammatory to bronchodilator drugs may, however, be misleading if the specificity of a drug for the treatment of asthma, compared with other diseases, is unknown. AIM: To test the association of specific drugs with the diagnosis of asthma compared with other diagnoses. DESIGN OF STUDY: Cross-sectional study analysing prescription data from a retrospective chart review. SETTING: Eight general practices and one community respiratory practice in a town in Northern Germany. METHOD: All patients in the participating practices who received at least one of the 50 asthma drugs most frequently prescribed in Germany within the past 12 weeks were identified. Odds ratios (ORs) with 95% confidence intervals (ClI) were calculated to reveal any association between a specific drug and the diagnosis of asthma. The unit of analysis was the item prescribed. RESULTS: Topical betamimetics (e.g salbutamol, fenoterol) were the most often prescribed asthma drugs in the general practices (52.1 ) and in the respiratory practice (57.6%). Inhaled steroids accounted for 15% and 13%; systemic steroids accounted for 10% and 13%, respectively. In the general practices, inhaled betamimetics had a moderate marker function for asthma (OR = 2.0; 95% CI = 1.14-3.58). A fixed oral combination drug of clenbuterol plus ambroxol was a marker drug against asthma (OR = 0.35; 95% CI = 0.20-0.61). In the respiratory practice, the diagnosis of asthma was strongly marked by fixed combinations of cromoglycate plus betamimetics (OR = 29.0; 95% CI = 6.86-122.24) and moderately by inhaled betamimetics (OR = 2.6; 95% CI = 1.28-5.14). In contrast, systemic steroids (OR = 0.24; 95% CI 0.10-0.57) and even inhaled steroids (OR = 0.46; 95% ClI= 0.22-0.96) proved to contradict the diagnosis of asthma. CONCLUSION: Only betamimetics were markers for asthma patients in both types of practices; inhaled steroids, however, were not. Combinations of cromoglycate were markers in the respiratory practice only. Limited specificity of drugs for a disease (e.g asthma) should be taken into account when analysing prescribing data that are not diagnosis linked. PMID- 11761201 TI - Comorbidity associated with atrial fibrillation: a general practice-based study. AB - BACKGROUND: [corrected] Atrial fibrillation is an important risk factor for ischaemic stroke. Anticoagulation treatment with warfarin can substantially reduce the risk of stroke in people with atrial fibrillation but concerns about their side-effects have limited their use in clinical practice. However there has been little population-based research on the comorbidity associated with atrial fibrillation and on the prevalence of potential contraindications to anticoagulantion treatment among these patients. AIM: To determine the prevalence of known risk factors for ischaemic stroke and possible contraindications to anticoagulant treatment among patients with atrial fibrillation. METHOD: One-year prospective cohort study in 60 general practices in England and Wales with a total population of 502,493 people. Age and sex specific prevalence rates and relative risks of risk factors for ischaemic stroke and possible contraindications to antithrombotic treatment were calculated. RESULTS: The number of patients who had a diagnosis of atrial fibrillation during the year was 1,414 (0.3%) patients. The prevalence of other nsk factors for ischaemic stroke in patients with atrial fibrillation increased with age in men, from 48% (relative risk [RR] = 3.78, 95% confidence interval [95% CI] = 3.23-4.41) at 45 to 64 years to 64% (RR = 2.21, 95% CI = 2.00-2.44) at 75years and over A similar increase of 50% (RR = 4.36, 95% CI = 3.54-5.38) to 60% (RR = 2.07, 95% CI = 1.91 2.23) was seen in women. The percentage of men with atrial fibrillation with at least one contraindication to antithrombotic treatment was 5% at 45 to 64 years and 14% at 75 years and over. Among women with atrial fibrillation, 7% had a contraindication at 45 to 64 years and 16% at 75 years and over. The all-ages relative risk of a contraindication was 1.17 (95% CI = 0.92-1.48) in men and 1.53 (95% CI = 1.28-1.83) in women. Forty per cent (575) of patients with atrial fibrillation had at least one risk factor for ischaemic stroke and no contraindications to antithrombotic treatment. CONCLUSION: Atrial fibrillation is associated with a substantial increase in the prevalence of risk factors for ischaemic stroke. By contrast, potential contraindications for antithrombotic treatment are more evenly distributed among patients with and without atrial fibrillation. Around 40% of patients with atrial fibrillation in primary care are at high risk of stroke and have no contraindicationsfor antithrombotic treatment. PMID- 11761202 TI - Underperforming doctors in general practice: a survey of referrals to UK Deaneries. AB - BACKGROUND: National Health Service Executive guidelines for rehabilitation of general practitioners (GPs) who require professional support state that these GPs should be advised to contact the Director of Postgraduate General Practice Education in their Deanery. There has been concern about how the needs of these GPs can be met without additional resources. AIM: To monitor and describe the process and outcome of these referrals over a two-year period to assess the size of the problem, to share good practice, and to identify any deficiencies in the system. DESIGN OF STUDY: Quarterly postal questionnaires. SETTING: Deaneries in the United Kingdom, which are geographically-based organisational units for the management of general practice education. METHODS: Three postal questionnaires were devised to cover General Medical Council (GMC) referrals to Deaneries, health authority referrals, and referrals made by Deaneries to the GMC Non responders were contacted by telephone. RESULTS: Twenty-seven GPs were referred by the GMC, 72 were referred by health authorities, and 18 referrals were made by Deaneries to the GMC. The information provided to Deaneries by the GMC was timely in just over half the cases, and was left to be appropriate in two-thirds of cases. Information provided by health authorities was almost always timely, detailed, and appropriate. The action required by the GMC was felt to be inappropriate in five cases, and not feasible in eight cases. No extra resources were available in the majority of cases. Information about outcome for the GP was either unavailable or unclear in over half the cases. CONCLUSION: This monitoring exercise has revealed several deficiencies in the system for dealing with the educational needs of underperforming GPs. There is a needfor a clear national protocol for referral of GPs to Deaneries and for the support that Deaneries can be expected to provide. PMID- 11761203 TI - Adherence to guidelines on cervical cancer screening in general practice: programme elements of successful implementation. AB - BACKGROUND: There is still only limited understanding of whether and why interventions to facilitate the implementation of guidelines for improving primary care are successful. It is therefore important to look inside the 'black box' of the intervention, to ascertain which elements work well or less well. AIM: To assess the associations of key elements of a nationwide multifaceted prevention programme with the successful implementation of cervical screening guidelines in general practice. DESIGN OF STUDY: A nationwide prospective cohort study. SETTING: A random sample of one-third of all 4,758 general practices in The Netherlands (n = 1,586). METHOD: General practitioners (GPs) in The Netherlands were exposed to a two-and-a-half-year nationwide multifaceted prevention programme to improve the adherence to national guidelines for cervical cancer screening. Adherence to guidelines at baseline and after the intervention and actual exposure to programme elements were assessed in the sample using self administered questionnaires. RESULTS: Both baseline and post-measurement questionnaires were returned by 988 practices (response rate = 62%). No major differences in baseline practice characteristics between study population, non responders, and all Netherlands practices were observed. After the intervention all practices improved markedly (P<0.001) in their incorporation of nine out of 10 guideline indicators for effective cervical screening into practice. The most important elements for successful implementation were: specific software modules (odds ratios and 95% confidence intervalsfor all nine indicators ranged from OR = 1.85 [95% CI = 1.24-2.77] to OR = 10.2 [95% CI = 7.58-14.1]); two or more 'practice visits' by outreach visitors (ORs and 95% CIs for six indicators ranged from OR = 1.46 [95% CI= 1.01-2.12] to OR = 2.35 [95% CI = 1.63-3.38]); and an educational programme for practice assistants (ORs and 95% CIs for four indicators ranged from OR = 1.57 [95% CI = 1.00-1.92] to OR = 1.90 [95% CI = 1.25 2.88]). CONCLUSION: A multifaceted programme targeting GPs, including facilitating software modules, outreach visits, and educational sessions for PAs, contributes to the successful implementation of national guidelines for cervical screening. PMID- 11761204 TI - Parents' perspectives on the MMR immunisation: a focus group study. AB - BACKGROUND: The uptake of the combined measles, mumps and rubella immunisation (MMR) in Britain has fallen since 1998, when a link was hypothesised with the development of bowel disorders and childhood autism. Despite reassurances about the safety of MMR, uptake levels remain lower than optimal. We need to understand what influences parents' decisions on whether to accept MMR or not so that health professionals can provide a service responsive to their needs. AIM: To investigate what influences parents' decisions on whether to accept or refuse the primary MMR immunisation and the impact of the recent controversy over its safety. DESIGN: Qualitative study using focus group discussions. SETTING: Forty eight parents, whose youngest child was between 14 months and three years old, attended groups at community halls in six localities in Avon and Gloucestershire. METHODS: Purposive sampling strategy was used to include parents from a variety of socioeconomic backgrounds. Three groups comprised parents who had accepted MMR and three groups comprised parents who had refused MMR. Data analysis used modified grounded theory techniques incorporating the constant comparative method. RESULTS: All parents felt that the decision about MMR was difficult and stressful, and experienced unwelcome pressure from health professionals to comply. Parents were not convinced by Department of Health reassurances that MMR was the safest and best option for their children and many had accepted MMR unwillingly. Four key factors influenced parents' decisions: (a) beliefs about the risks and benefits of MMR compared with contracting the diseases, (b) information from the media and other sources about the safety of MMR, (c) confidence and trust in the advice of health professionals and attitudes towards compliance with this advice, and (d) views on the importance of individual choice within Government policy on immunisation. CONCLUSIONS: Parents wanted up-to-date information about the risks and benefits of MMR to be available in advance of their immunisation appointment. Many parents did not have confidence in the recommendations of health professionals because they were aware that GPs needed to reach immunisation targets. Most parents would, however, welcome more open discussion about immunisation with health professionals. PMID- 11761206 TI - Complementary medicine use in children: extent and reasons. A population-based study. AB - This study used a cross-sectional population survey to determine the prevalence of complementary medicine use in children. Some form of complementary medicine had been used by 17.9% of children at least once, and 6.9% had visited a complementary medicine practitioner. Homoeopathy, aromatherapy, and herbal medicine were most frequently used, most commonly for ear; nose, and throat; dermatology; musculoskeletal; infant; respiratory; and emotional/behavioural health problems. Complementary medicine was used mainly because of word-of-mouth recommendation, dissatisfaction with conventional medicine, and fear of side effects of conventional treatments. Complementary medicine use is widespread in children; professionals should be aware of this, be alert for possible side effects/interactions, and encourage adherence to effective conventional treatments where important. PMID- 11761205 TI - Hampshire depression project: changes in the process of care and cost consequences. AB - Records of patients included in a trial of educating practice teams about the management of depression were examined to determine changes in the process of care. There were no significant differences in the proportions recognised or treated for depression. Only 15% of those with possible, and 26% of those with probable, major depressive disorder were prescribed recommended doses and duration of antidepressants. The education apparently delayed a switch away from tricyclics while achieving a similar outcome. However health service costs were mainly non-psychiatric, and there were no significant savings as a result. PMID- 11761207 TI - The MODEL project: a scoring system to manage demand for cataract and joint replacement surgery. AB - Cataract surgery and joint replacement are highly cost-effective procedures; however, their availability is inequitable and doctors lack guidance on whom to refer and treat. We investigated the feasibility of using a scoring system to assess patients' suitability for operation. Wefound acceptable correlations between the scores ofgeneral practitioners and surgeons for both procedures. Scoring systems can be used in a consistent way bygeneralpractitioners and surgeons, and can make a contribution towards matching patients' needs with available treatment capacity. PMID- 11761208 TI - Informal carers and the primary care team. AB - The number of carers in the community is rising, and the importance of general practice in providing supportfor them has been highlighted. Caring for a disabled friend or relative has been shown to be harmful to the health of the caregiver and changes in social and family structure have led carers to become isolated and more reliant on the formal support services. However, many carersfeel that GPs do not understand their needs, and in turn many GPs and nursesfeel that they lack the relevant resources and training to take a more proactive role. The shift from hospital to community-based care and the blurring of social roles of responsibility puts additional pressure on the carers and community services. However general practice is in the best position to help and there are many things that can be done by primary care teams, such as providing information about available support, benefits and local services, which would be appreciated by informal carers. PMID- 11761209 TI - Orthotic devices for tennis elbow: a systematic review. AB - Lateral epicondylitis (tennis elbow) is af requently reported condition. A wide variety of treatment strategies has been described. Asy et, no optimal strategy has been identified. The aim of this review was to assess the effectiveness of orthotic devices for treatment of tennis elbow. An electronic database search was conducted using MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trial Register Current Contents, and reference listsf rom all retrieved articles. Experts on the subjects were approachedfor additional trials. All randomised controlled trials (RCTs) descrbiing individuals with diagnosed lateral epicondylitis and assessing the use of an orthotic device as a treatment strategy were evaluatedfor inclusion. Two reviewers independently assessed the validity of the included trials and extracted data on relevant outcome measures. Dichotomous outcomes were expressed as relative risks and continuous outcomes as standardised mean differences, both with corresponding 95% confidence intervals. Statistical pooling and subgroup analyses were intended. Five small-size RCTs (n = 7-49 per group) were included the validity score ranged from three to nine positive items out of 11. Subgroup analyses were not performed owing to the small number of trials. The limited number of included trials present few outcome measures and limited long-term results. Pooling was not possible owing to the high level of heterogeneity of the trials. No definitive conclusions can be drawn concerning effectiveness of orthotic devices for lateral epicondylitis. More well-designed and well-conducted RCTs of sufficient power are warranted. PMID- 11761210 TI - Otitis externa. PMID- 11761211 TI - Improving access in primary care. PMID- 11761212 TI - Chlamydia trachomatis: opportunistic screening in primary care. PMID- 11761213 TI - The end of single-handed practice? PMID- 11761214 TI - The end of single-handed practice? PMID- 11761215 TI - Management of patients with depression. PMID- 11761216 TI - Proton pump inhibitors: perspectives of patients and their GPs. PMID- 11761217 TI - Repeat prescribing realignment project. PMID- 11761218 TI - What does patient-centredness really mean? PMID- 11761219 TI - A new world order. PMID- 11761220 TI - Afghanistan--humanitarian aid and military intervention don't mix. PMID- 11761221 TI - Perestroika in primary care. PMID- 11761222 TI - TRIPs revisited. PMID- 11761223 TI - Time heals! Using time as a currency. PMID- 11761224 TI - Explanations for the credulous. PMID- 11761225 TI - Role of CTL host responses and their implication for tumorigenicity testing and the use of tumour cells as vaccine substrate. AB - Viral oncogenes, mutated cellular oncogenes, or other adventitious agents that might contaminate vaccine preparations on inoculation of the host will encounter a T cell-mediated immune response which will play a determining role in the progression of neoplastic events or replication of contaminating viral agents. Using SV40 T antigen tumour systems as a model we discuss the regions of the oncoprotein that have an impact on tumourigenicity and the role of CD8 T lymphocyte immune responses in eliminating potential tumour cells. In addition, we discuss measures that counteract T cell immune responses to abrogate T cell mediated immunosurveillance. PMID- 11761226 TI - Transgenic animal models that might be useful in identifying unsuspected oncogenic factors in tumour cell substrates. AB - The use of alternative short term models for the assessment of pharmaceutical carcinogenicity potential is expanding and evolving. Several mouse models of accelerated carcinogenesis have gained user confidence and are being applied to product development decision-making. These models have been highlighted as part of a consortium effort organized under ILSI to further evaluate their strengths and limitations compared to the standard two-years, two species cancer bioassay. Examples of trends that are developing in our understanding of applicability of these models to chemical carcinogenesis have been presented but a more comprehensive review of all the currently available data has been avoided. Such a review would be soon outdated as the anticipated data from the ILSI consortium studies will soon become available and greatly further impact our present appreciation of the capabilities of these models. As strengths and limitations of those models are being elucidated, mechanistic understanding of the models is expanding. In addition to those reviewed briefly in this paper, numerous other transgenic models with micro-injected oncogenes and disrupted tumour suppressor genes have demonstrated enhanced propensity for developing cancer. Critical experiments can be designed to test, conceptually, for the ability of any of these models to detect tumorigenic potential for a given dose of adventitious agent, or residual DNA sequence. The choice of model and of DNA sequence or adventitious agent to begin this evaluation must be carefully considered. From such data, risk may be better identified or prioritized, but such approaches may not be practical as general routine screens of finished vaccine product with unknown residual DNA sequence or adventitious agents. PMID- 11761227 TI - Evaluating the oncogenic risk of residual DNA in vaccines: the potential role of transgenic mice. AB - There is a general consensus that residual DNA from immortalised cells is very unlikely to pose a safety risk for biotechnology products but there is little experimental data to support this contention. Transgenic mice primed with one or more oncogenes or tumour suppressor deletions offer a potentially sensitive and quantitative method for determining the presence of oncogenic DNA. Separate lines of mice transgenic for myc and Cbfa1 may provide a means of detecting oncogenic DNA containing genes belonging to different complementation groups. PMID- 11761228 TI - Generation of mink cell focus-inducing retroviruses: a model for understanding how viral-viral and viral-cellular interactions can result in biological consequences. AB - Using neoplastic cell lines as substrates for vaccine development could inadvertently result in viral-viral or viral-cellular interactions whose biological consequences are unclear. In this review, the generation of mink cell focus-inducing (MCF) retroviruses in the mouse is discussed as a model for understanding how viral-viral and viral-cellular interactions can result in the generation of new retroviruses with pathological consequences. PMID- 11761229 TI - MuLV packaging systems as models for estimating/measuring retrovirus recombination frequency. AB - Interaction of retrovirus vectors and endogenous retroviruses present in packaging cell lines and target cells may result in the formation of recombinant viruses. Using sensitive RT-PCR assays, we have investigated human and murine gene therapy packaging cell lines for the incorporation of endogenous retrovirus transcripts into murine leukaemia virus (MLV) vector particles and whether vector genomes are incorporated into human endogenous retrovirus (HERV) particles. VL30 endogenous retrovirus sequences were packaged in particles produced by the murine AM12 packaging system. For every seven MLV-derived -galactosidase beta-Gal vector genomes present in the particles, one copy of VL30 was also packaged. Although human FLY packaging cells expressed HERV transcripts (HERV-K, HuRT, type C, and RTVL-H), none was detectable in the MLV vector particles released from the cells. Non-specific packaging of the MLV gag-pol expression vector transcripts was detected in the FLY virions at a low level (one in 17,000 sequences). In other experiments, gag proteins produced by HERV-K particles present in human teratocarcinoma cells did not appear to package MLV-based vectors that expressed Gal transcripts. These findings indicate that retrovirus vectors interact with human packaging cells to produce retrovirus particles that are far less contaminated by endogenous viral sequences or other types of extraneous particles than murine packaging cells. PMID- 11761230 TI - Mixed retrovirus infections. AB - Mixed retrovirus infections frequently result in viral pseudotyping in which the genome of a virus is encapsulated within virions possessing a distinct host range from that encoded by the packaged genome. Pseudotyping between different classes of murine retroviruses has been extensively documented in vitro and in vivo and can result in profound changes in viral replication and pathology. A number of non-human retroviruses exhibit infectivity for various heterologous cell lines which often include human cells. Thus there is a possibility of generating heterologous mixed retroviral infections in humans upon the administration of clinical reagents developed in non-human systems. Pseudotyping between retroviruses from heterologous species (e.g., murine and primate retroviruses) has also been documented in mixed in vitro infections, as has pseudotyping between retroviruses and viruses of other families (e.g., rhabdoviruses). The effects of heterologous pseudotyping on viral replication and pathology in vivo have not been extensively studied and represent a potential concern for the development of clinical reagents in heterologous cells. PMID- 11761231 TI - Pathogenesis of replication competent retroviruses derived from mouse cells in immunosuppressed primates: implications for use of neoplastic cells as vaccine substrates. AB - T-cell lymphomas developed in three of 10 immunosuppressed rhesus macaques during early experiments using retroviral vectors to transfer marker genes into CD34+ bone marrow cells for subsequent transplantation in the animals. Direct PCR analyses of RNA obtained from tumour tissues from these macaques revealed the presence of several different recombinant murine leukaemia viruses (MuLV). Most prominent was a recombinant designated Mo(LTR)Ampho(env) in which the amphotropic env of the helper packaging virus was joined to a modified form of long terminal repeat (LTR) of the Moloney MuLV-derived vector that contained an additional copy of the core enhancer. This new LTR afforded enhanced replication upon the Mo(LTR)Ampho(env) MuLV in several different rhesus cell types compared with the prototype amphotropic MuLV4070A. Unexpectedly, at least two types of a mink cell focus-forming (MCF) MuLV element, arising from endogenous retroviral sequences expressed in the murine packaging cell line, were also transmitted and highly expressed in one of the macaques. Furthermore, murine virus-like VL-30 sequences were detected in the rhesus lymphomas, but these were not transcribed into RNA. The unanticipated presence of this array of MuLV-related structures in a primate gene transfer recipient highlighted the generation of recombinant retroviruses when the vector producer line produced replication competent viruses. These recombinants had an enhanced tropism and pathogenicity in the primate gene transfer recipients and frequently caused lymphomas. This primate experiment highlights the potential risk from contamination of a vaccine cell substrate with a replicating retrovirus. PMID- 11761232 TI - Pathogenesis of defective retroviruses. AB - Concerns about the presence of contaminating defective retroviruses in cells used for vaccine preparations have been raised. These concerns mainly reflect the fact that (i) most species harbour several copies of endogenous defective and/or non defective retroviral sequences in their genome; (ii) these sequences have frequently been found to participate in recombination events giving rise to novel viral entities; and (iii) several strains of defective retroviruses have been shown to be pathogenic. Here, a brief description of the main features of defective retroviruses is provided. In addition, the characteristics and plasticity of defective retroviruses are illustrated with a defective retrovirus inducing a mouse disease, murine AIDS (MAIDS). PMID- 11761233 TI - Retroviral recombination as an adjunct to viral propagation and pathogenesis. PMID- 11761234 TI - Evolution of live-attenuated virus vaccines. PMID- 11761235 TI - Retroviral insertion into herpesviruses: discovery and implications. AB - Retroviruses and herpesviruses are important human pathogens. Co-infections of these viruses in hosts often exist and co-infection of the same cell type is also common. In this report, we will review the evidence that supports the contention that retrovirus insertion into herpesvirus can occur in vitro and in vivo. We will also discuss retrovirus insertion into other large DNA viruses. PMID- 11761236 TI - Foamy virus replication: implications for interaction with other retroviruses and host cellular sequences. AB - Foamy viruses (FV) comprise one of the seven genera of retroviruses. These viruses infect most non-human primates as well as cats, cows and horses. Infections are persistent and life-long, but have no pathogenic consequences. Viral replication in vivo is at a very low level, but virus can be recovered years after infection. Humans can acquire FV as zoonotic infections which are also life-long. Although FV are highly cytopathic to fibroblast cultures, some cell lines can be infected with FV without any syncytium formation or cell death. Thus, material obtained from infected animals could contain FV proviruses without any obvious cytopathicity. The consequences of FV in biological material is not known. Little is known about how FV package their genomes, or whether they are able to package cellular genes which could have consequences for recipient cells. In addition, possible recombination between FV and other retroviruses has not been studied. Future studies of this virus should focus on the packaging ability of FV and whether they can recombine with other retroviruses. PMID- 11761237 TI - Analysis of lenti- and trans-lentiviral vector genetic recombination. AB - Lentiviral vectors hold great promise for gene therapy, and clinical trials to examine their safety and efficacy for treating human disease are being planned. The principle concern for safety is that genetic recombination among components of the vector could lead to the emergence of replication competent retrovirus (RCR). Using a sensitive method for detecting genetic recombination, we found that the current design of lentiviral vectors permits the generation of envelope deficient recombinant lentivirus, stable integration of the recombinant into chromosomes of transduced cells, and mobilization of the recombinant genomes to other cells when pseudotyped with an exogenous envelope. We split the lentiviral packaging construct (Gag/Gag-Pol) into two separate parts: one that expresses Gag and Gag-Pro, and another that expresses Pol (reverse transcriptase [RT] and integrase [IN]) as a fusion partner of Vpr (Vpr-RT-IN). This "trans-lentiviral" vector efficiently transduces non-dividing cells and achieves titres greater than 10(6) U/ml or 10(8) IU/ml after concentration by ultracentrifugation. The trans lentiviral vector disarms the Gag-Pol structure and prevents the generation of recombinants containing functional RT and IN. Since RT and IN are absolutely required for any type of RCR and DNA mobilization, this new class of lentiviral vector, in combination with our sensitive in vitro assay for monitoring regeneration of the gag-pol structure, offers a unique advantage for predicting vector safety for clinical applications. PMID- 11761238 TI - Major issues associated with the use of cell substrates for the production of vaccines. PMID- 11761239 TI - Telomerase activity and cellular immortalization. AB - Normal human cells undergo a limited number of divisions and eventually undergo senescence. This is accompanied by several changes, including increases in inhibitors of cyclin-dependent kinases and shortening of telomeres. Expression of the catalytic component of telomerase, hTERT, significantly extends the lifespan of human fibroblasts but is not sufficient for the immortalization of human keratinocyte or breast epithelial cells. However, inactivation of the Rb/p16ink4a pathway, or down-regulation of p16ink4a expression in combination with hTERT, is capable of immortalizing human epithelial cells efficiently. Elimination of p53, and of the DNA-damage-induced checkpoint is not required for immortalization, nor is a consistent loss of p19ARF. PMID- 11761240 TI - An overview of cell DNA issues. AB - Because at least some tumour cells are known to contain oncogenes and/or viral genes, there is a theoretical possibility that even small amounts of cellular DNA in a product could transmit genetic information for cancer, or for certain viruses, and thus cause an oncogenic event or pathology related to viral gene expression. The major points supporting such a possibility are that (i) viral nucleic acids can infect cells, (ii) tumour cell DNA can transform 3T3 cells, (iii) viral DNA can infect animals and, (iv) the purified viral oncogene, v-src, caused tumours in chickens. On the other hand, there is no convincing evidence that DNA from tumour cells can cause tumours in animal test systems, and a limited amount of human and non-human primate data are consistent with a level of risk that is not measurable. Estimates of various types of risk from residual cellular DNA suggest that the levels of risk are so low that they are not measurable in most cases. PMID- 11761241 TI - The transforming activity of tumour cell DNA. AB - Transfection of DNA isolated from a subset of human tumour cells was shown in the early 1980s to be capable of inducing transformation in NIH3T3 cells. This review summarizes the approaches and results of the efforts to measure the transforming activity of genomic DNA and discusses the results in the light of current concerns about the potential hazard associated with DNA contamination of biological material produced by cultured transformed cells. PMID- 11761242 TI - Infectivity of lentiviral DNA in animals. PMID- 11761243 TI - Utility of human neural cells and cell lines for anti-viral vaccine research and development. AB - Specific cell types such as neurons, astrocytes, and microglial cells can be isolated from a mixed population of human foetal brain cells and cultured for extended periods. The rapid expansion of cell populations occurring during culture has accommodated the large-scale growth and production of various neurotropic viruses. Furthermore, neural cell lines derived from CNS tumours or by the immortalization of primary cells have also been established and used for studies of viral pathogenesis. The potential to generate and expand selected populations of neural-derived cells should provide a new and abundant substrate for the production of viruses in vaccine development. PMID- 11761244 TI - Review of workshop purposes and goals. PMID- 11761245 TI - Retrotransposon insertions in germ cells and somatic cells. PMID- 11761246 TI - Application of quantitative methods for the detection of adventitious agents. PMID- 11761247 TI - Industrial experience with live polio vaccine prepared on the Vero continuous cell line. PMID- 11761248 TI - Human peripheral blood mononuclear cell substrate for propagating wild type HIV 1. AB - Molecularly derived HIV proteins fail to induce broadly neutralizing antibodies (NAB) and cytotoxic T cell (CTL) responses, which are considered necessary for any effective vaccination. Natural virion proteins of the primary isolates of HIV 1 (pi-HIV), grown in human peripheral blood mononuclear cells (PBMC) followed by viral inactivation and pooling to reflect the antigenic diversity of the prevalent strains in a given population, would provide a novel polyvalent HIV vaccine (HIVAX) capable of inducing both HIV-NAB and CTL. Proven technologies are harnessed to provide a framework for advancing human blood-derived HIVAX. Fresh leukocytes, recovered by gravity flow elution from leukocyte depletion blood filters, or "buffy coats", routinely removed in preparing blood components for transfusion, provide an abundant and safe cell substrate following ficoll separation of viable PBMC. The low content of wild-type HIV (wt-HIV) in infected plasma can be chaperoned by dendritic cells through their DC-SIGN receptor for gp120 and efficiently expanded in co-culture with CD4-enriched cell substrate in a medium containing human AB serum as a substitute for foetal calf serum. Dimethyl methylene blue (DMMB), ethylene diiimine (EDI), or psoralens can be used to inactivate the virion RNA selectively and the unbound chemicals and their products are removable by molecular sieving. Additional inactivation by physical methods would include proven hydrostatic pressure cycling technology (PCT) and flash pasteurization at 60 degrees C for less than 10 minutes to totally inactivate infectivity of the virions. Our empirical strategy is to pool five different HIV isolates of the prevalent subtype B (U.S.A.) or C (Southern Africa), augmented by other subtypes A, C/B, D, E, and 'X' (new emerging subtypes), to provide a polyvalent HIV vaccine (HIVAX). Immunochemical quantification of the gp120, gp41, p24 and p31 antigen content of HIVAX ensures consistency of the product, and safety is ensured by failure to amplify HIV nucleic acid sequences by RT-PCR and to demonstrate infectivity in animal models. Ultimate efficacy HIVAX must be shown by human clinical trials in the high-risk populations. PMID- 11761249 TI - Response to apoptin of diploid fibroblasts from cancer-prone syndromes. PMID- 11761250 TI - Human papillomaviruses: A window into the mechanism and regulation of eucaryotic cellular DNA replication. AB - Papillomaviruses are ubiquitous pathogens of humans and other vertebrates. Productive infections lead to hyperproliferative lesions in squamous epithelia from diverse anatomic sites, both cutaneous and mucosal. The 7,900 bp double stranded, circular DNA genome replicates as extrachromosomal plasmids in the nuclei of infected cells. The productive phase of the HPV infection takes place in differentiated, post-mitotic squamous keratinocytes. However, viral DNA replication requires the host cells to supply much of the replication machinery and substrates. Consequently, these viruses usurp the cellular control mechanisms via protein interactions and provide an excellent model system to investigate cellular processes. This paper summarize our investigations and insight into the virus-host interactions observed in productively infected patient lesions, in a model organotypic culture system of primary human keratinocytes transduced with viral genes, and in a cell-free viral DNA replication system with purified viral and host protein. PMID- 11761251 TI - Developing an approach to evaluate the use of neoplastic cells as vaccine substrates. AB - Advances in technology, emerging infectious diseases and accumulating knowledge of the mechanisms of neoplastic development are stimulating the need to develop a regulatory management plan that can be used to evaluate different types of neoplastic cells as possible substrates for vaccine development. To address this challenge, CBER is developing an approach, based on issue identification, issue based model development and validation, and, where possible, a quantitative risk evaluation, as a basis for regulatory guidance on the use of neoplastic cell substrates for the manufacture of viral vaccines. The issues or concerns that have been identified with the use of neoplastic cell substrates include vaccine contamination with viable human tumour cells or adventitious agents, the possible risks associated with residual cell-substrate DNA or proteins in the vaccine, possible vaccine virus interactions with the cell substrate, and possible uncertainties associated with the instability of the neoplastic cell genome. PMID- 11761252 TI - Facilitated detection of adventitious agents using genetically engineered cell lines. AB - Proposals to expand the number and types of cellular substrates used in the production of live attenuated vaccines, especially to include those of tumour origin, have raised concerns about the current capacity to detect adventitious agents that may be present in vaccine stocks. Detection of unknown agents is especially difficult because the culture systems used may not be optimal. We hypothesize that failure to grow certain viruses in culture may be the result of the cellular suicide mechanism, known as apoptosis, killing virus-infected cells before the virus can effectively replicate and spread. Our earlier work with an HIV-1 culture system which overexpresses the cellular anti-apoptotic gene, bcl-2, demonstrated that interfering with the apoptotic programme could facilitate HIV-1 expression and accelerate the kinetics of an acute spreading HIV-1 infection. These findings may have implications for improving cell culture detection systems to screen for potentially harmful infectious agents in current and developmental vaccine substrates. In this paper, we briefly review earlier work and discuss future studies aimed at manipulating the cellular apoptotic programme to facilitate the replication of adventitious and transforming viral agents in vitro. PMID- 11761253 TI - In situ analysis of the transcriptional activity of integrated viral DNA using tyramide-FISH. AB - Infection by the oncogenic human papillomavirus (HPV) types 16 and type 18 can progress to cancers. Two well studied cervical carcinoma cell lines, SiHa and CaSki, contain two to four copies, or several hundred copies of integrated HPV 16, respectively. To define the chromosomal loci from which HPV mRNAs are transcribed in these cells, we have simultaneously visualized chromosomal DNA territories, HPV DNA or nascent HPV RNA sequences by using a highly sensitive in situ hybridization (T-FISH) technique employing deposition of fluorescent tyramides. We found that, in SiHa cells, nascent HPV RNAs co-localized with both integrated HPV copies on chromosome 13. Surprisingly, in CaSki cells, nascent HPV RNA only co-localized with one minor HPV DNA-positive locus on chromosome 14. The DNA signal intensity of this locus was consistent with a single to a few HPV intergrants. The tyramide methodologies described here provide an in-depth molecular cytological analyses applicable to research and diagnosis. PMID- 11761254 TI - Pert analysis of endogenous retroviruses induced from K-BALB mouse cells treated with 5-iododeoxyuridine: a potential strategy for detection of inducible retroviruses from vaccine cell substrates. AB - The activation of an endogenous, infectious retrovirus in a cell substrate that is used for the production of biologics is an important safety concern, especially in the case of live, viral vaccines, where there are minimal purification and inactivation steps in order to preserve high vaccine potency. Extensive analysis has been done to evaluate various chemical agents for the induction of endogenous retroviruses in murine and avian cells; however, similar studies have not been done with cells of other species, especially human and non human primates, that are used in vaccine production. To develop a strategy for optimal induction and sensitive detection of endogenous, infectious retroviruses in currently used or potential vaccine cell substrates, we have initially investigated the use of a state-of-the-art, highly-sensitive, product-enhanced reverse transcriptase (PERT) assay for evaluating the kinetics of retrovirus induction and replication in 5-iododeoxyuridine (IdU)-treated K-BALB mouse cells, where endogenous retrovirus activation has previously been described. In general, the overall kinetics of virus production were similar to those of previous studies in that two peaks of RT activity were seen on long-term culture of IdU treated K-BALB cells; however, retrovirus activation was detected earlier under our induction conditions and with greater sensitivity using the PERT assay, where 1-10 virions were detected in 1 microl equivalent of the test sample, without concentration. Furthermore, the PERT activity corresponded to the presence of infectious, murine leukaemia viruses (MuLVs) induced from K-BALB cells. Based upon these results, a strategy is proposed using the PERT assay for detection of inducible, endogenous retroviruses in vaccine cell substrates. PMID- 11761255 TI - Infectivity of wild-type and deleted proviral SIV DNA. AB - Live attenuated lentiviruses are potentially effective candidate HIV vaccines; however, delivery of these viruses in the field would be problematic. Delivery of attenuated lentiviruses as proviral DNA would be a simple means of immunization, but the efficiency of this method of delivery is not known. In this study, macaques were readily infected following inoculation of plasmid DNA encoding proviral simian immunodeficiency virus (SIVmac239), whether given i.m. (300 microg) or epidermally (15 microg), with all four animals succumbing to AIDS at a mean of 26 weeks following inoculation. Using a human skin explant model, we found that the 50% infectious dose (ID50) of proviral SIV or HIV-1 plasmid may be as low as 1 microg when delivered to skin by gold particle bombardment using a gene gun. An infectious proviral clone of SIV mac239 with a 105 bp deletion in the 3' nef/LTR overlap region was engineered (SIVsbbc delta3), analogous to the initial common nef/LTR deletion in HIV-1 strains isolated from an Australian cohort of long-term slow-progressors. Two further macaques were also readily infected with SIVsbbc delta3 after i.m. injection of 300 microg of highly purified plasmid DNA. Unexpectedly, in one macaque inoculated with SIVsbbc delta3 DNA, SIV strains isolated three to six weeks after infection had completely repaired the nef/LTR deletion with wild-type sequence, and eventually progressed to AIDS. The mechanism used to rebuild this deletion with wild-type sequence, presumably derived from an intact 5' LTR, is unclear, but possibilities include RNA read-through errors from the plasmid DNA and recombination with residual plasmid DNA at the inoculation site. PMID- 11761256 TI - Adventitious agent issues. AB - Characterised cell banks are likely to be the most virologically satisfactory production system. In the past there have been numerous examples of contamination of biologicals by agents which may be difficult to detect. The certainty with which a cell can be thought satisfactory depends on the efficacy of the available methods of examination. PMID- 11761257 TI - Retroviral aspects of the characterisation of avian and mammalian cell substrates. AB - There have been no reported incidents of adventitious retroviral infection of cell lines used for the production of vaccines and other biologicals. However, due to the unique molecular biology of retroviruses, cell lines may contain endogenous retroviral genomes and these can give rise to defective retroviral particles, e.g. murine hybridomas and CHO cells. Recently, a similar situation was reported for a cell substrate in use for decades for vaccine production, namely chick embryo fibroblasts, and this raised some concern regarding the safety of these vaccines. PMID- 11761258 TI - Induction/activation and detection of occult viral agents present in mammalian cells. AB - Occult viral agents in cell cultures may include (i) known viruses present at a concentration too low for detection and (ii) unknown viruses. For maximal safety regarding adventitious agents, a strategy is proposed which involves cellular cloning of candidate cell substrates for vaccines. This will render occult viruses present in either all cells or none, thus greatly facilitating their detection. Known and unknown members of virus families known to establish latency are best detected by molecular methods based on broadly conserved sequences and low stringency conditions. The presence of retrovirus particles, known or unknown, in vaccine harvests can be excluded by the Product-Enhanced Reverse Transcriptase (PERT) assay which detects particle-associated reverse transcriptase with the sensitivity of nucleic acid amplification tests. Latent retroviruses can be activated by stimulation with halogenated pyrimidines and/or azacytidine. Endogenous proviruses with no release of particles are of no concern. PMID- 11761259 TI - Status of HERV in human cells: expression and coding capacity of human proviruses. AB - Human endogenous retroviruses (HERVs) comprise a significant portion of the human genome. They are expressed in a variety of human tissues and some encode intact retroviral proteins. HERV expression seems to be upregulated in certain tissues and tumour types. The HERV-K(HML-2) family is an important exception from the vast majority of defective HERVs in that it encodes all essential retroviral proteins and functional enzymes, respectively. Furthermore, several intact HERV K(HML-2) gag and env genes as well as an almost intact HERV-K(HML-2) provirus could be demonstrated within the human genome. However, none of the HERVs described so far seems to produce infectious virus. PMID- 11761260 TI - Viral latency--the papillomavirus model. AB - To investigate the prevalence and the natural history of human papillomavirus infections, we monitored HPV DNA shedding as a consequence of immunosuppression, with the expectation that latent viral infections would reactivate and become detectable. The study populations consisted of women who were in end-stage renal failure, those who ultimately received kidney transplantations, and those who had HIV/AIDS with various degrees of immune depression at entry. For each woman, cervico-vaginal lavage to sample viral shedding from the lower genital tract was performed at approximately six month intervals, and the cohorts have been followed since 1996. Nested polymerase chain reaction amplification of papillomavirus DNA using novel pairs of primers was followed by diagnostic restriction endonuclease cleavage or by DNA sequencing. This strategy is particularly capable of identifying single and multiple infections and determining the genotypes of any viruses present. Of the 225 women in the HIV cohort, 177 (79%) were HPV-positive and 111 (49%) shed from two up to eight different HPV types over the course of the survey. Thirty-five different mucosotropic HPV types, virtually all that have ever been described worldwide, were isolated from these 225 women, and nine additional new (provisional) types were discovered. As is always the case, HPV-6 was very common. However, all the other frequently detected HPV types (45, 52, 53, 54, 58, 74) were more prevalent than the types typically reported forthe general population (HPV-11, 16, 18, 31, 33, 35). Notably, the 14 members of the A3 phylogenetic subgroup (HPV-61, 62, 72, 81, 83, 84, and all the new types) were by far the most frequently observed viral types in the AIDS cohort. The HPV prevalence in the cohorts of kidney transplantation candidates and recipients was only slightly lower than that in the AIDS cohort. We conclude that HPV infections are extraordinarily common and are normally held in a sub-clinical state by functional immune systems, but can be reactivated by immunosuppressive conditions. The question of how so many distinct types persist in the human population and can be repeatedly isolated from specimens collected around the world raises complex issues concerning the nature of viral transmission, reproduction, shedding, and mutational drift. These molecular epidemiological observations signal the likelihood that HPV is part of the commensal microflora of human epithelia. Their prevalence elicits a caution that latent HPV DNA may be present in primary human epithelial tissues. PMID- 11761261 TI - Conceptual and experimental approaches to address product safety issues raised by novel cell substrates. AB - This article provides a brief summary of the defined risks approach to evaluating new cell substrates for vaccine production, and indicates how quantitative data may be applied to assess risks in a regulatory setting. A more detailed discussion of how the potential infectious risk of residual DNA may be evaluated is provided as an example of this process. PMID- 11761262 TI - Transmissible spongiform encephalopathies: vaccine issues. AB - The recent emergence of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob Disease (vCJD) suggests that transmissible spongiform encephalopathies (TSEs) pose an ongoing threat to human and animal health. To avoid iatrogenic transmission of TSEs in vaccines, strategies must be developed to obviate TSE agent infectivity in cellular substrates, cell culture media components and enzymes, and excipients, and to validate the safety of these components and field vaccines efficiently PMID- 11761263 TI - The cellular immortalization process: relevant issues for the generation of cell substrates for production of vaccines and other biologicals. AB - Although non-immortalized primary cultures have been widely used, and continue to be used, for the production of biological materials, there are many instances where the use of immortalized cell lines presents a significant saving in effort as well as cost. Furthermore, circumstances can often arise where the cell substrate must be engineered to a degree which cannot be achieved in primary cultures; in such cases the use of immortalized cells would be a necessity. The downside of using immortalized cells is that the vast majority of currently available immortalized cell lines display malignant phenotypes, which in many cases can limit their usefulness for the production of biologicals. In this review we will explore the biological basis of the immortalization process, as well as recent advances in our ability to engineer immortalization using well defined interventions. PMID- 11761264 TI - Safety of recombinant adenoviruses produced on adenovirus-transformed human cells. PMID- 11761265 TI - A brief history of cell substrates used for the preparation of human biologicals. PMID- 11761266 TI - A defined-risks approach to the regulatory assessment of the use of neoplastic cells as substrates for viral vaccine manufacture. PMID- 11761267 TI - Animal models of neoplastic development. AB - The basic animal model for neoplastic development used by regulatory agencies is the two-year chronic bioassay developed more than 30 years ago and based on the presumed mechanism of action of a few potential chemical carcinogens. Since that time, a variety of other model carcinogenic systems have been developed, usually involving shorter duration, single organ endpoints, multistage models, and those in genetically-engineered mice. The chronic bioassay is still the "gold standard" of regulatory agencies despite a number of deficiencies, while in this country the use of shorter term assays based on single organ endpoints has not been popular. The multistage model of carcinogenesis in mouse epidermis actually preceded the development of the chronic two-year bioassay, but it was not until multistage models in other organ systems were developed that the usefulness of such systems became apparent. Recently, several genetically-engineered mouse lines involving mutations in proto-oncogenes and tumour suppressor genes have been proposed as additional model systems for use in regulatory decisions. It is likely that a combination of several of these model systems may be most useful in both practical and basic applications of cancer prevention and therapy. PMID- 11761268 TI - Multistage carcinogenesis in cell culture. AB - Rodent fibroblasts explanted from embryos to culture undergo a period of declining growth rate in serial passages leading to crisis, followed by the appearance of variants which can multiply indefinitely. If the "immortal" cell line was established by low density passage, i.e., 3T3 cells, it has a low saturation density and is non-tumorigenic. If it was established by high density passage, it has a high saturation density and is tumorigenic. The establishment of cells goes through successive stages, including increased capacity to multiply in low serum concentration, growth to high saturation density, growth in suspension, assisted tumour formation in susceptible hosts and unassisted tumour formation. Chromosome aberrations and aneuploidy occur long before the capacity to produce tumours appears. Contrary to conventional belief, human fibroblast populations also undergo a continuous loss of capacity to multiply from the time of explantation, with only the longest surviving clone reaching the Hayflick limit. Neoplastic transformation of rodent cells is strongly favoured by maintaining them in a quiescent state at confluence for prolonged periods, which results in genetic damage to the cells. It also produces a large variety of chromosomal aberrations in human cells and extends their replicative lifespan. Individual clones are more susceptible to spontaneous transformation than their heterogeneous parental cultures. The implications of these results for tumour development in vivo are that oncogenic genetic changes may be common under stressful conditions which restrict replication, and that such changes are maximized when a rogue clone reaches a critical size that reduces stabilizing interactions with neighbouring clones. An alternative explanation, described in the Addendum, which we retrospectively favor is that the easily transformed clones are a minority in the uncloned parental population. The reason they transform before the parental population is that when they are expanded, they have more transformable cells available under the selective condition of confluence than the uncloned parental population from which they are derived. PMID- 11761269 TI - Transformation by DNA viral oncogenes. PMID- 11761270 TI - "Hit and run" transformation leading to carcinogenesis. AB - Subgenomic fragments of herpes simplex virus and cytomegalovirus have been shown to transform rodent cells to a neoplastic phenotype in vitro. The transfected DNA does not persist long term in the transformed cells, and viral proteins, although transiently expressed, cannot be detected in the established cell lines. There is evidence that the transforming DNA fragments have mutagenic properties. It has not been established that the effects found in rodent cells can be observed in human cells. Although, the concept of "hit-and-run" transformation has been controversial for many years, it remains the only plausible explanation for the observations of neoplastic transformation, following in vitro transfection of herpesvirus and cytomegalovirus DNAs, which have been made by multiple laboratories over more than two decades. PMID- 11761271 TI - DNA methylation and epigenetic mechanisms of carcinogenesis. PMID- 11761272 TI - The fate of foreign DNA in mammalian cells and organisms. AB - We have investigated the consequences of foreign DNA insertions into the genomes of mammalian cells in transgenic cell lines, in adenovirus type 12 (Ad12) transformed cells, in Ad12-induced tumor cells or in transgenic mice. We have reported previously on the de novo methylation of integrated foreign genomes and on extensive changes in cellular patterns of DNA methylation upon foreign DNA insertion. These studies have been extended and several independent methods have been applied to document these alterations in cellular DNA methylation and gene expression patterns in transgenic cell lines and in transgenic mice. These data are relevant for the mechanism of (viral) oncogenesis and for the interpretation of data gathered in experiments with transgenic animals. PMID- 11761273 TI - Role of the innate immune response in determining the tumorigenicity of neoplastic cells. AB - Expression of the E1A oncogene of adenovirus serotype 5 (Ad5) sensitizes neoplastic cells from different species, including human, to apoptosis triggered by components of the innate mmune response. This E1A activity causes a marked reduction in the tumorigenicities of sarcoma cells in a manner that is directly linked to the competence of NK cells from the test animals to lyse E1A-expressing tumour cells. The results from this oncogene model indicate that studies of quantitative differences in the tumorigenicities of different neoplastic cells should include considerations of oncogene regulation of susceptibility to immune mediated injury and the immunocompetence of the animals chosen as tumour challenge recipients. PMID- 11761274 TI - The evaluation of microbial contamination in platelet concentrates prepared by two different methods. AB - The microbial contamination of platelet concentrates (PCs) prepared by two different methods both with a high risk of bacterial contamination during preparation and storage were evaluated. For apheresis platelets, the concentrates were obtained using the Haemonetics MCS 3P device. For the random method, platelets were obtained by two phase centrifugation, in the Heraeus Cryofuge 8500 I device using the Kansuk 3-way bags which permit storage for five days. 1620 plateletpheresis units prepared by apheresis, and 9838 units prepared by the random method, were included in the study. Of the 11,458 PCs studied. 32 (0.27%) were false positives and 24 (0.2%) were real positives. All of the positive results occurred in platelets prepared by the random method. C. xerosis and S. epidermidis, S. hominis, Alpha-hemolytic streptococci, all flora of the skin, were isolated in the contaminated concentrates. The risk of microbial contamination of PCs, prepared both by apheresis and from whole blood, continues at a low rate although the products were collected into specific bags following rules including appropriate disinfection of the skin, correct centrifugation collection time and optimal storage conditions including temperature and agitation. These results again emphasize the importance of: obeying phlebotomy rules and hand disinfection of the person who collects the blood as well as the need for careful skin decontamination of the donor, during donation. PMID- 11761275 TI - IVIG-pools: regulatory gifts--transiting from harmony toward harmonious immunoglobulins: why? and why not? AB - Based on 'initial conditions' which depend on each donors' exposure to a unique environment, a pooled intravenous immunoglobulin (IVIG) product transfers its immunoglobulin molecule repertoire, unchanged, to the altered host. The relay function of the cell-bound receptors, especially that of the inhibitory Fc(gamma)RIIB, may then allow sufficient amplification to make regulatory activity possible. To the clinician, IVIG may be considered a tool to promote reversal of the dysregulation causing autoimmune disease. Generically, IVIG may be seen as a promoter allowing a progression from harm by an inflammatory/fibrotic reaction, then down-regulating toward restitutio ad integrum. By modifying natural processes, IVIG may play minor roles in promoting defense against spontaneous bleeding and, perhaps, stimulating remyelination. The wide spectrum of IVIG specificities, by reflecting evolutionary epitope selection, may not further destabilize cell/molecule disarray in the affected host. Benefit to the patient by IVIG treatment cannot be predicted nor can potentially severe or even fatal accidents entirely be excluded. Important aspects of IVIG treatment still await clarification including dosage, timing and the isotype form. In the foreseeable future it does not seem that biotechnological advances will match the physiologic harmony of IVIG, leaving antibody characteristics aside. PMID- 11761276 TI - Fetomaternal alloimmune thrombocytopenia. AB - Thrombocytopenia is the second commonest haematological abnormality in the neonatal period after anaemia due to iatrogenic blood letting. One to four percent of all newborn babies have a platelet count < 150 x 10(9)/l at birth and approximately 20-40% of neonates in intensive care units are affected by neonatal thrombocytopenia. The most common cause of severe neonatal thrombocytopenia is fetomaternal platelet incompatibility and subsequent alloimmunisation. During the last decade recent advances in molecular techniques have led to rapid and efficient methods for diagnosis. Progress in fetal medicine has enabled accurate determination of fetal status, allowing improvements in fetal diagnosis and therapy. Human platelet antigen (HPA)-1a is by far the most frequently involved platelet antigen system in Caucasians accounting for 90% of cases, followed at a much lower frequency by HPA-5b (5-15%) and HPA-3a. The incidence is estimated to be 1 per 2000 to 1 per 5000 live births, but this is low in comparison to the incidence of fetomaternal platelet antigen incompatibility especially for the HPA 1 alloantigen system in the Caucasian population in whom the estimated frequency of HPA-1b1b individuals is 2%. Retrospective and prospective studies have reported that the immunogenetic background is important, and the chance of HPA-1a alloimmunisation is strongly associated with maternal HLA class II DRB3*0101 (DR52a) type. A significant association (p = 0.004) between severe thrombocytopenia and a third trimester antiHPA titre >1:32 has been observed. It is now possible to genotype the fetus or neonate and the parents, which provides confirmation as to which HPA systems are incompatible between the mother and father. Simultaneous genotyping of HPA-1, 2, 3 and 5 can be carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) protocol, which has been widely used for HLA class II determination. The platelet count may continue to fall during the first 48 h after birth and the risk of intracranial bleeding is highest during this period. The best option is transfusion of specially selected antigen negative compatible donor platelets or if unavailable, maternal washed platelets. Antenatal screening for the most common form of fetomaternal alloimmune thrombocytopenia (FMAIT), due to antiHPA-1a is under consideration, but there is no established method at present. The Scottish National Blood Transfusion Service started a study in August 1999 on 25,000 pregnancies to carry out a cost benefit analysis of routine antenatal screening. The aims of the study are to determine the frequency of HPA-1b homozygosity; monitor antibody titres during pregnancy and confirm correlation of antibody emergence with HLA DRB3*0101, and finally to access cost effectiveness of routine screening across Scotland. Of 26,509 women screened in three Scottish regions 501 (1.9%) are HPA 1b homozygous and about 9%, of the consented women are antibody positive. PMID- 11761277 TI - Bacterial contamination of blood components. AB - Despite considerable advances in the safety of blood components, transfusion associated bacterial infection (TABI) remains an unresolved problem. As yet there are no perfect preventative, screening and/or detection methodologies for eliminating contaminated units. Until a practical, rapid, cost-effective and logistically acceptable test becomes available, we should be satisfied with the choice of various limited solutions that at least partially improve the bacterial safety of blood components. It is also necessary to establish standardised guidelines and agreed upon systematic procedures for the recognition and reporting of the laboratory and clinical evaluation of adverse reactions in recipients of contaminated blood components. PMID- 11761278 TI - Hemophilia centre twinning with Nanfang Hospital, Guangzhou, China. Challenges and opportunities. PMID- 11761279 TI - A period of trial in American apheresis medicine. PMID- 11761280 TI - Standardisation of platelet counting accuracy in blood banks by reference to an automated immunoplatelet procedure: comparative evaluation of Cell-Dyn CD4000 impedance and optical platelet counts. AB - Prophylactic and therapeutic platelet transfusions are increasingly used for patients with conditions associated with thrombocytopenia in order to prevent the development of potentially life threatening bleeding. These clinical strategies have led to a significant expansion in platelet unit manufacture, and this now represents a major resource and cost commitment for blood banks. As part of the manufacturing process, blood banks are required to implement control procedures, and the determination of platelet counts in particular is necessary to confirm that the quality of platelet unit production meets the standards defined by national or international guidelines. Apart from linearity analysis and comparisons of platelet counts given by different instruments, there has been no systematic standardisation of platelet counting methods in blood bank practice because to date there has been no suitable reference method for counting platelets in citrate anticoagulants. The recent introduction of an automated immunoplatelet procedure on the Cell-Dyn CD4000 provides a means of determining a true platelet count that is unaffected by changes induced either by storage or anticoagulant. The CD4000 in its routine configuration also provides simultaneous impedance and optical platelet counts and this study was therefore undertaken in order to compare all three different platelet counting methods in parallel with a representative series of platelet units. Platelet counts determined after sub sampling of platelet units into EDTA vs plain non-anticoagulated tubes revealed no differences in impedance or immunoplatelet counts but generally lower optical counts when aliquoted into tubes that did not contain EDTA. This study therefore routinely used EDTA for platelet unit sub-samples. Comparative results of platelet counts for buffy coat platelet units (n = 36) aliquoted into EDTA indicated that the impedance count was higher than the reference immunoplatelet count by a mean factor of 1.25 while the optical count was lower by a mean factor of 0.87. The degree of impedance count overestimation was particularly consistent while the optical count underestimation was more variable. Linearity studies of 10 fresh platelet units showed no deviation in the range 0-2305 x 10(9) l(-1) for impedance and 0 to 1420 x 10(9) l(-1) for the optical counts, and the relative numerical relationships between impedance and optical counts were conserved throughout the range of dilutions tested. In the CD4000 optical analysis, blood samples anticoagulated with EDTA showed a distinctive elliptical population distribution that fell within the system thresholds. In contrast, the optical pattern observed for platelet units (in CPD) and ACD-anticoagulated venous blood showed a wider 90 degrees scatter with a population of platelet events above the upper parallel discriminator. As these were excluded from the optical count (but were still identified as platelets by the immunoplatelet method) it meant that the optical counts of samples in citrate-based anticoagulants were systematically lower than immunoplatelet counts. Platelet units (n = 15) analysed daily over a seven day period of storage revealed that the greatest decline in platelet counts was with the optical measurement while the most stable value was obtained by impedance analysis. The results of the immunoplatelet analysis further suggested a progressive increase in small platelets with increasing storage time. The use in this study of a standardised immunoplatelet reference method to examine the question of analyser suitability for determining platelet counts/yields of platelet units thus provided a number of important findings. An impedance platelet counting method is utilised by the great majority of haematology instruments in current use, and in common with the CD4000 analyser, a correction factor is employed to take account of RBC/platelet coincidence. This study found that when analysed samples such as platelet units were RBC-free, that an inappropriate correction factor was applied. Consequently, the CD4000 impedance platelet count will provide reliable platelet counts, irrespective of the day of platelet unit storage, when a factor of 1.25 is applied to the system-reported result. By comparison, optical methods are more likely to be affected by subtle morphological changes that may result from anticoagulants or progressive storage time. The method limitations documented by this study may well affect many other analysers and mean that the implementation of process control statistics related to platelet counts may be less reliable than previously assumed. It is suggested that standardisation could be much better achieved if there was some form of system cross-calibration that was referenced to an independent method such as an immunoplatelet assay. It is proposed that studies of this type should be extended to a wide assessment of platelet count accuracy of blood bank instruments in order to standardise data within national organisations. If consistent inter instrument correction factors such as those documented here can be identified, it would considerably increase the relevance of determining platelet counts in production control processes. PMID- 11761281 TI - Prevalence and correlates of antisocial behaviors among three ethnic groups. AB - Using data from the MECA Study, this report examines the prevalence of Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), and various levels of antisocial behavior and their correlates among three ethnic groups: Hispanics, subdivided into Island Puerto Ricans and Mainland Hispanics; African Americans; and Mainland Non-Hispanic, Non-African Americans. Correlates considered include stressful life events, birth defects, low birth weight, learning difficulties, teen mothers, family environment, marital adjustment, social competence, parental monitoring, and family relationships. Logistic regression was used to determine the association of outcomes with individual correlates and of interaction terms with ethnicity. Differences between adjusted rates and observed rates of disorders and levels of antisocial behaviors are compared to estimate the extent to which each correlate explains the group differences in rates. Island Puerto Ricans had a lower prevalence of CD, ODD, and various levels of antisocial behavior than mainland Hispanics, African Americans, and non-Hispanic Whites. The lower prevalence appears to be associated with differences in the extent to which a number of these correlates are found on the island, the most salient being better family relations between the target children and their parents and siblings. PMID- 11761282 TI - Relationship quality of aggressive children and their siblings: a multiinformant, multimeasure investigation. AB - Sibling influence on the learning and enactment of aggressive behavior has been consistently demonstrated in studies of sibling relationships. Available evidence suggests that, compared with nonaggressive children's sibling interactions, the sibling interactions of aggressive children are marked by more frequent, intense, and prolonged aggressive behaviors. Although research on normative and aggressive children's sibling interactions has increased recently, a number of limitations in this literature were addressed in this study by: (1) including both an aggressive and nonaggressive comparison group, (2) examining both positive and negative features of sibling relationships, (3) employing a multimethod/multiinformant approach to data collection, and (4) utilizing an improved self-report method. In support of our hypotheses and consistent with previous research, results showed that aggressive children's sibling relationships were marked by higher levels of observed conflict and lower levels of self-reported positive features. When gender was examined, results showed that older brother/younger sister dyads were characterized by higher levels of negative features and lower levels of positive features. PMID- 11761283 TI - A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies. AB - The processing of emotional expressions is fundamental for normal socialisation and interaction. Reduced responsiveness to the expressions of sadness and fear has been implicated in the development of psychopathy (R. J. R. Blair, 1995). The current study investigates the sensitivity of children with psychopathic tendencies to facial expressions. Children with psychopathic tendencies and a comparison group, as defined by the Psychopathy Screening Device (PSD; P. J. Frick & R. D. Hare, in press), were presented with a cinematic display of a standardised set of facial expressions that depicted sadness, happiness, anger, disgust, fear, and surprise. Participants observed as these facial expressions slowly evolved through 20 successive frames of increasing intensity. The children with psychopathic tendencies presented with selective impairments; they needed significantly more stages before they could successfully recognise the sad expressions and even when the fearful expressions were at full intensity were significantly more likely to mistake them for another expression. These results are interpreted with reference to an amygdala and empathy impairment explanation of psychopathy. PMID- 11761284 TI - Somatic markers and response reversal: is there orbitofrontal cortex dysfunction in boys with psychopathic tendencies? AB - This study investigated the performance of boys with psychopathic tendencies and comparison boys, aged 9 to 17 years, on two tasks believed to be sensitive to amygdala and orbitofrontal cortex functioning. Fifty-one boys were divided into two groups according to the Psychopathy Screening Device (PSD, P. J. Frick & R. D. Hare, in press) and presented with two tasks. The tasks were the gambling task (A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) and the Intradimensional/Extradimensional (ID/ED) shift task (R. Dias, T. W. Robbins, & A. C. Roberts, 1996). The boys with psychopathic tendencies showed impaired performance on the gambling task. However, there were no group differences on the ID/ED task either for response reversal or extradimensional set shifting. The implications of these results for models of psychopathy are discussed. PMID- 11761285 TI - Can inattention/overactivity be an institutional deprivation syndrome? AB - Elevated rates of attention deficit and overactivity have been noted previously in samples of institution-reared children. This study examined the hypothesis that inattention/overactivity(I/O) might constitute a specific deprivation syndrome. One hundred and sixty five children adopted at varying ages (e.g., 0-42 months of age) into the UK following severe early deprivation were compared with 52 within-UK adoptees who did not suffer deprivation. The children were rated by teachers and parents on levels of I/O, conduct difficulties, and emotional difficulties using the Revised Rutter Scales. Data were collected at age 6 for the entire sample and at age 4 for the UK adoptees and for the subsample of Romanian children who entered the UK before the age of 2 years. Mean level analyses suggested a significant effect of duration of deprivation on I/O, but not on conduct or emotional difficulties. The effects of duration of deprivation were specific to I/O and were not accounted for by low birth weight, malnutrition, or cognitive impairment. Levels of I/O correlated with attachment disturbances. Furthermore, the effects of duration of deprivation on I/O did not attenuate over time. We conclude that I/O may well constitute an institutional deprivation syndrome, but that the type of attention deficit and overactivity exhibited by these children may present a different clinical picture from that of "ordinary" varieties of attention deficit disorder or hyperkinetic syndrome. PMID- 11761286 TI - A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD. AB - Recent research on the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD) has demonstrated that the subtypes differ in demographic characteristics, types of functional impairment, and profiles of comorbidity with other childhood disorders. However, little research has tested whether the subtypes differ in underlying neuropsychological deficits. This study compared the neuropsychological profiles of children without ADHD (n = 82) and children who met symptom criteria for DSM-IV Predominantly Inattentive subtype (ADHD-IA; n = 67), Predominantly Hyperactive Impulsive subtype (ADHD-HI; n = 14), and Combined subtype (ADHD-C; n = 33) in the areas of processing speed, vigilance, and inhibition. We hypothesized that children with elevations of inattention symptoms (ADHD-IA and ADHD-C) would be impaired on measures of vigilance and processing speed, whereas children with significant hyperactivity/impulsivity (ADHD-HI and ADHD-C) would be impaired on measures of inhibition. Contrary to prediction, symptoms of inattention best predicted performance on all dependent measures, and ADHD-IA and ADHD-C children had similar profiles of impairment. In contrast, children with ADHD-HI were not significantly impaired on any dependent measures once subclinical symptoms of inattention were controlled. Our results do not support distinct neuropsychological deficits in ADHD-IA and ADHD-C children, and suggest that symptoms of inattention, rather than symptoms of hyperactivity/impulsivity, are associated with neuropsychological impairment. PMID- 11761287 TI - Executive functioning, temporal discounting, and sense of time in adolescents with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). AB - Clinic-referred teens (ages 12-19) with ADHD and ODD (N = 101) were compared to community control (CC) teens, equated for age and sex, (N = 39) on a variety of psychological tasks assessing executive functioning (EF), temporal reward discounting, and time estimation and reproduction. A factor analysis reduced the EF measures to three dimensions, representing CPF Inattention, Working Memory, and CPT Inhibition. Results indicated that the ADHD group had significantly more CPT Inattention than the CC group. No differences were found for Working Memory or CPT Inhibition. The ADHD group displayed significantly greater temporal discounting of delayed hypothetical monetary rewards relative to immediate ones and manifested more impaired time reproduction, but not time estimation, than did the CC group. Main effects for level of IQ were found only on the Working Memory factor and largely did not interact with the group factor otherwise. The group differences in CPT Inattention, temporal discounting, and time reproduction were not a function of level of comorbid oppositional defiant disorder, delinquency, or anxiety-depression. Results are reasonably consistent with past research on EF and sense of time in children with ADHD and extend these findings to the adolescent age group. Problems with working memory and CPT inhibition found in prior studies of children with ADHD, however, were not evident here, perhaps owing to age-related improvements or insufficient task difficulty. PMID- 11761288 TI - Parent-adolescent conflict in teenagers with ADHD and ODD. AB - Eighty-seven male teens (ages 12-18 years) with ADHD/ODD and their parents were compared to 32 male teens and their parents in a community control (CC) group on mother, father, and teen ratings of parent-teen conflict and communication quality, parental self-reports of psychological adjustment, and direct observations of parent-teen problem-solving interactions during a neutral and conflict discussion. Parents and teens in the ADHD/ODD group rated themselves as having significantly more issues involving parent-teen conflict, more anger during these conflict discussions, and more negative communication generally, and used more aggressive conflict tactics with each other than did parents and teens in the CC group. During a neutral discussion, only the ADHD/ODD teens demonstrated more negative behavior. During the conflict discussion, however, the mothers, fathers, and teens in the ADHD/ODD group displayed more negative behavior, and the mothers and teens showed less positive behavior than did participants in the CC group. Differences in conflicts related to sex of parent were evident on only a few measures. Both mother and father self-rated hostility contributed to the level of mother-teen conflict whereas father self-rated hostility and anxiety contributed to father-teen conflict beyond the contribution made by level of teen ODD and ADHD symptoms. Results replicated past studies of mother-child interactions in ADHD/ODD children, extended these results to teens with these disorders, showed that greater conflict also occurs in father-teen interactions, and found that degree of parental hostility, but not ADHD symptoms, further contributed to levels of parent-teen conflict beyond the contribution made by severity of teen ADHD and ODD symptoms. PMID- 11761290 TI - The influence of family and experimental context on cognition in anxious children. AB - Examined the influence of family on anxious children's cognition. Research by Barrett, Rapee, Dadds, and Ryan (1996) found anxious children reported increased avoidance after interacting with their parents. They labelled this finding the FEAR effect-Family Enhancement of Avoidant Responses. Whilst some subsequent studies have found similar results, others have not. These contradictory findings question whether the direction of parental influence on anxious children is determined by the perceived demands of the experimental context. Anxious children (N = 101) and their parents were asked to interpret seven ambiguous situations and to discuss what their child would do if the scenario actually occurred. Study 1 found that children in the anxious group and an externalizing control group were more likely to interpret ambiguous situations as threatening than nonclinic children were. Study 2 sought to examine changes in the children's responses from pre- to postfamily discussion, and to identify variables associated with the FEAR effect in anxious families. Interestingly, anxious children whose families completed the discussion task after they (children) had been offered treatment were more likely to show a FEAR effect than anxious families who completed the task as part of assessment. Study 3 examined predictors of enhanced avoidance in anxious families. Treatment context and maternal distress were correlated with the child's increased avoidance following family discussion. Limitations of these studies and directions for future research are discussed. PMID- 11761289 TI - Is expressed emotion a specific risk factor for depression or a nonspecific correlate of psychopathology? AB - Five Minute Speech Sample Expressed Emotion (FMSS-EE) was examined in families of youth with depressive disorders, nondepressed youth with attention deficit/hyperactivity disorder (ADHD), and community controls screened for the absence of depression and ADHD. Consistent with the hypothesis that FMSS-EE shows some specificity as a risk factor for depression, rates of critical EE were significantly higher among mothers of youth with depression as compared to mothers of nondepressed youth with ADHD, or mothers of controls. When both mothers' and fathers' scores were used to generate family EE ratings, rates of overall EE and critical EE were significantly higher for the depressed group than the control group, but the nondepressed ADHD group did not differ significantly from the other groups. Results support the hypothesis that critical EE in mothers shows some specificity as a risk factor or correlate of depression in youth. PMID- 11761291 TI - In vitro antibiotic sensitivity of strains of Ornithobacterium rhinotracheale isolated in The Netherlands between 1996 and 1999. AB - All the strains of Ornithobacterium rhinotracheale isolated in the Netherlands between 1996 and 1999 were tested in the agar gel diffusion test for their sensitivity to amoxycillin, tetracycline, enrofloxacin and trimethoprim/sulphonamide (TMP/S). The percentages of strains sensitive to amoxycillin and tetracycline decreased in successive years from approximately 62 per cent to 14 per cent, and four strains were resistant to enrofloxacin or TMP/S. Twelve multiresistant strains were tested against seven alternative antibiotics; they were resistant to all of them except clavulanic acid potentiated amoxycillin. PMID- 11761292 TI - New histochemical and ultrastructural observations on normal bovine tonsils. AB - Samples of normal bovine palatine tonsils were examined by light and electron microscopy. Like human tonsils, they were composed of crypts, subepithelial areas, follicles, and T-dependent zones, but their well-developed capsule subdivided the lymphoid tissue by connective septa. B cells formed the major lymphoid component. The follicles and T-dependent zones had morphological and histochemical features typical of peripheral lymph organs. Follicular dendritic cells were isolated and shown to be similar to human follicular dendritic cells. PMID- 11761293 TI - Clostridium perfringens beta2-toxin in an African elephant (Loxodonta africana) with ulcerative enteritis. AB - A 22-year-old female African elephant (Loxodonta africana) developed diarrhoea of unknown cause which lasted for two days. The animal was euthanased after it remained recumbent and refused to get up. Gross pathological changes were present mainly in the gastrointestinal tract. The intestinal contents were watery and dark brown. Several areas of the mucosa of the small intestine were covered minimally to moderately with fibrin and had a few 0.1 x 10 to 15 cm linear ulcerations. Microscopical lesions consisted of discrete areas of necrosis of the surface and crypt epithelium without overt inflammatory infiltrates. Culture of the small intestinal contents resulted in a moderate growth of Clostridium perfringens. No salmonella were found in the small or large intestine. PCR of the isolate of C. perfringens revealed the presence of the beta2-toxin gene cpb2 and the alpha-toxin gene cpa but no other known toxin genes. The expression of the beta2-toxin gene in vivo was demonstrated by the immunohistochemical localisation of the beta2-toxin to the microscopical lesions in the small intestine. PMID- 11761294 TI - Diagnosis of foot-and-mouth disease by real-time fluorogenic PCR assay. PMID- 11761295 TI - Granulomatous (pseudotumoral) iridociclitis associated with leishmaniasis in a cat. PMID- 11761296 TI - Klebsiella pneumoniae infection in Italian rabbits. PMID- 11761297 TI - Toxoplasmosis in a wild-caught black lion tamarin (Leontopithecus chrysopygus). PMID- 11761298 TI - EU requirement to survey for BSE in fallen stock: consequences for postmortem examination. PMID- 11761299 TI - Salmonella typhimurium DT170 in cattle. PMID- 11761300 TI - National Scrapie Plan. PMID- 11761301 TI - Feline leukaemia virus neutralising antibodies. PMID- 11761302 TI - Approaches to diagnosis and treatment. PMID- 11761303 TI - The effects of promotion and prevention cues on creativity. AB - This study tested whether cues associated with promotion and prevention regulatory foci influence creativity. The authors predicted that the "risky," explorative processing style elicited by promotion cues, relative to the risk averse, perseverant processing style elicited by prevention cues, would facilitate creative thought. These predictions were supported by two experiments in which promotion cues bolstered both creative insight (Experiment 1) and creative generation (Experiment 2) relative to prevention cues. Experiments 3 and 4 provided evidence for the process account of these findings. suggesting that promotion cues, relative to prevention cues, produce a riskier response bias (Experiment 3) and bolster memory search for novel responses (Experiment 4). A final experiment provided evidence that individual differences in regulatory focus influence creative problem solving in a manner analogous to that of incidental promotion and prevention cues. PMID- 11761304 TI - The automated will: nonconscious activation and pursuit of behavioral goals. AB - It is proposed that goals can be activated outside of awareness and then operate nonconsciously to guide self-regulation effectively (J. A. Bargh, 1990). Five experiments are reported in which the goal either to perform well or to cooperate was activated, without the awareness of participants, through a priming manipulation. In Experiment 1 priming of the goal to perform well caused participants to perform comparatively better on an intellectual task. In Experiment 2 priming of the goal to cooperate caused participants to replenish a commonly held resource more readily. Experiment 3 used a dissociation paradigm to rule out perceptual-construal alternative explanations. Experiments 4 and 5 demonstrated that action guided by nonconsciously activated goals manifests two classic content-free features of the pursuit of consciously held goals. Nonconsciously activated goals effectively guide action, enabling adaptation to ongoing situational demands. PMID- 11761305 TI - Emotional selection in memes: the case of urban legends. AB - This article explores how much memes like urban legends succeed on the basis of informational selection (i.e., truth or a moral lesson) and emotional selection (i.e., the ability to evoke emotions like anger, fear, or disgust). The article focuses on disgust because its elicitors have been precisely described. In Study 1, with controls for informational factors like truth, people were more willing to pass along stories that elicited stronger disgust. Study 2 randomly sampled legends and created versions that varied in disgust; people preferred to pass along versions that produced the highest level of disgust. Study 3 coded legends for specific story motifs that produce disgust (e.g., ingestion of a contaminated substance) and found that legends that contained more disgust motifs were distributed more widely on urban legend Web sites. The conclusion discusses implications of emotional selection for the social marketplace of ideas. PMID- 11761306 TI - Substituting the forest for the trees: social networks and the prediction of romantic relationship state and fate. AB - This research focused on perceptions held by heterosexual couples' friendship network concerning the couple's relationship. In a three-wave longitudinal study, we examined (a) whether these perceptions were similar to the couple's views of the relationship, (b) whether they predicted current relationship state and future fate, and (c) how they compared with the couple's perceptions in predicting fate. Consistent with within-dyad idealization, results from a North American sample indicated that network perceptions of relationship state were significantly more negative than those held by a couple. Although both the couples' and the total networks' perceptions predicted fate, friends of the female couple member were particularly successful at predicting relationship dissolution. An examination of possible mechanisms whereby friends may come to possess particularly predictive perceptions supported the role of couple disclosure in this process. PMID- 11761307 TI - If you can't join them, beat them: effects of social exclusion on aggressive behavior. AB - Social exclusion was manipulated by telling people that they would end up alone later in life or that other participants had rejected them. These manipulations caused participants to behave more aggressively. Excluded people issued a more negative job evaluation against someone who insulted them (Experiments 1 and 2). Excluded people also blasted a target with higher levels of aversive noise both when the target had insulted them (Experiment 4) and when the target was a neutral person and no interaction had occurred (Experiment 5). However, excluded people were not more aggressive toward someone who issued praise (Experiment 3). These responseswere specific to social exclusion (as opposed to other misfortunes) and were not mediated by emotion PMID- 11761308 TI - How people make support judgments: individual differences in the traits used to infer supportiveness in others. AB - Social support and other social judgments are composed of several distinct components, of which relationship effects are an important part. With regard to support judgments, relationship effects refer to the fact that when judging the same targets, people differ systematically in whom they see as supportive. One explanation for this effect is that people differ in how they combine information about targets to judge supportiveness. Participants rated the supportiveness of hypothetical targets and targets from their own social networks. Multilevel modeling identified the traits participants used to make support judgments. There were significant differences in the extent to which participants used different target personality traits to judge supportiveness. In addition, participant neuroticism predicted the extent to which participants used target neuroticism and agreeableness to judge supportiveness. PMID- 11761309 TI - Cognitive interdependence and convergent expectations in transactive memory. AB - A laboratory experiment investigated the processes that underlie the development of transactive memory structures--the organizing schemes that connect knowledge held by individuals to knowledge held by others (D. M. Wegner, T. Guiliano, & P. T. Hertel, 1985). The design was a 2 x 4 factorial that controlled expectations about the partner's knowledge (similar or different from the participant's) and cognitive interdependence, the degree to which participants' outcomes depended on whether they recalled the same or different information as their partner (defined by 4 incentives). Transactive memory was most differentiated when individuals had different expertise and incentives to remember different information and most integrated when individuals had similar expertise and incentives to remember the same information. These findings may help to explain the impact of previous experience and relationships on the development of transactive memory. PMID- 11761310 TI - Is there any scapegoat around? Determinants of intergroup conflicts at different categorization levels. AB - Recategorization at a higher level reduces tensions between groups. However, recategorization may cause conflicts between the common in-group and a new out group. Additionally, determinants of conflict between subgroups may enhance conflict at the higher categorization level. In the context of German unification, the authors explored these suggestions with an East German 3-wave longitudinal study and a West German control group. Results show that a salient East German versus West German categorization enhances conflict between subgroups, whereas categorization as German enhances conflict at the common in group level. Determinants of subgroup conflict also influence conflict at the inclusive level (Germans and foreigners). Thus, recategorization is a 2-edged instrument: Although it reduces conflict at the subgroup level, it may initiate conflict at the common in-group level. PMID- 11761311 TI - Self-Esteem and threats to self: implications for self-construals and interpersonal perceptions. AB - In 4 studies, the authors examined interpersonal perceptions as a function of self-construals and ego threats for those with high and low self-esteem. Previous research (T. F. Heatherton & K. D. Vohs, 2000a) found that after threat, high self-esteem people were rated as less likable by an unacquainted dyad partner, whereas low self-esteem people were rated as more likable. Study I showed that after threat, high self-esteem people seek competency feedback, whereas low self esteem people seek interpersonal feedback. Study 2 showed that high self-esteem people become more independent after threat, whereas low self-esteem people become more interdependent. Study 3 linked differences in independence versus interdependence to interpersonal evaluations. Study 4 found that differences in independent and interdependent self-construals statistically accounted for differences in likability and personality perceptions of high and low self-esteem people after threat. Thus, the combination of threat and self-esteem alters people's focus on different self-aspects, which consequently leads to different interpersonal appraisals. PMID- 11761312 TI - Rigid and extreme: a geometric representation of personality disorders in five factor model space. AB - Personality disorder rigidity and extremity can be geometrically defined and operationalized within the 5-factor model (FFM) of personality. A series of geometric and substantive assumptions were derived and then tested in samples of college students (N = 1,323) and psychiatric patients (N = 86). Normal and disordered personalities were found to coexist in a variety of regions of the FFM multivariate space. Within regions, the profiles of normal and disordered personalities were very similar in characteristic configuration but notably different in profile variability. Personality-disordered individuals tended to be located in the perimeters or outer regions of the FFM space, as indicated by their longer vector lengths. These findings generalized across 2 measures of personality disorders and across 2 measures of normal personality traits. PMID- 11761313 TI - Social roles as mechanisms for psychological need satisfaction within social groups. AB - The authors explored ways in which needs for autonomy and relatedness can be simultaneously met within the context of group life. Specifically, it was hypothesized that social role performances provide means of both expressing the self and connecting with group members. Consistent with the assumption that autonomy and relatedness are complementary rather than conflictual, these needs were positively correlated in all 5 studies. Consistent with the authors' assumption that these needs are both important, feelings of autonomy and relatedness in social roles independently predicted subjective well-being, as measured by concurrent (Studies I and 3), peer-report (Study 2). and longitudinal (Studies 4 and 5) methodologies. Study 5 showed that participants whose characteristics matched an assigned role experienced more autonomy and relatedness and thus more positive mood during a group task. Implications for optimal functioning in group contexts are discussed. PMID- 11761314 TI - Goal reconstruction and depressive symptoms during the transition to motherhood: evidence from two cross-lagged longitudinal studies. AB - Two cross-lagged longitudinal studies were carried out to investigate the extent to which the adjustment of personal goals to match the particular stage-specific demands of the transition to motherhood has consequences for women's depressive symptoms. In Study 1. 348 women filled out a revised version of Little's (1983) Personal Project Analysis and a revised version of Beck's Depression Inventory (A. T. Beck. C. H. Ward. M. Mendelsohn, L. Mock, & J. Erlaugh. 1961) 4 times: during early pregnancy, 1 month before childbirth, 3 months after childbirth. and 2 years after childbirth. In Study 2. 140 women who reported high levels of fear of childbirth filled out identical measures during early pregnancy, 1 month before childbirth, and 3 months after childbirth. The results showed that an increase in family-related goals during pregnancy and after the birth of the child predicted a decline in women's depressive symptoms. By contrast, an increase in self-focused goals predicted an increase in women's depressive symptoms. PMID- 11761315 TI - Blirtatiousness: cognitive, behavioral, and physiological consequences of rapid responding. AB - The Brief Loquaciousness and Interpersonal Responsiveness Test (BLIRT) measures the extent to which people respond to others quickly and effusively. The BLIRT displays desirable psychometric properties and distinguishes people who should theoretically score high (e.g., car salespersons) from those who should score low (e.g., librarians). Scores on the scale predict (a) the amount and rapidity of people's verbal responses in an unstructured interaction, (b) how likable and competent people's classmates perceive them to be early in the semester, (c) how quickly people respond to an obnoxious cell-phone user and how physiologically aroused they become, and (d) how quickly and emphatically people respond to a series of personal insults as well as their degree of physiological arousal. Converging evidence indicates that blirtatiousness is unique in its ability to amplify people's qualities, making these qualities more readily observable to perceivers. PMID- 11761316 TI - Syndromal versus contextualized personality assessment: differentiating environmental and dispositional determinants of boys' aggression. AB - Two studies examined how "syndromal" approaches to assessment confound differences between individuals in the person and situation variables that contribute to their behavior. In a field study, a widely used instrument was found to be sensitive to the base rates of boys' aggression but, as expected, did not discriminate between boys who were similar in their behavior base rates but different in their social environments and how they responded to them. A laboratory experiment replicated this finding and demonstrated that social observers discriminated between targets on the basis of their functional properties even though syndrome scores did not. The results clarify how syndromal methods can obscure situational factors, conflict with people's social knowledge, and reinforce the view that syndromes exist "in the individual" rather than in person-environment interactions. Implications for developing more contextually sensitive instruments are discussed. PMID- 11761317 TI - Personality-Relationship transaction in young adulthood. AB - Personality and social relationships were assessed twice across a 4-year period in a general population sample of 489 German young adults. Two kinds of personality-relationship transaction were observed. First, mean-level change in personality toward maturity (e.g., increase in Conscientiousness and decrease in Neuroticism) was moderated by the transition to partnership but was independent of other developmental transitions. Second, individual differences in personality traits predicted social relationships much better than vice versa. Specifically, once initial correlations were controlled for, Extraversion, Shyness, Neuroticism, self-esteem, and Agreeableness predicted change in various qualities of relationships (especially with friends and colleagues), whereas only quality of relationships with preschool children predicted later Extraversion and Neuroticism. Consequences for the transactional view of personality in young adulthood are discussed. PMID- 11761318 TI - Attachment theory and reactions to others' needs:' evidence that activation of the sense of attachment security promotes empathic responses. AB - Five studies examined the effects of chronic and contextual activation of attachment security on reactions to others' needs. The sense of attachment security was contextually primed by asking participants to recollect personal memories, read a story, or look at a picture of supportive others or by subliminally exposing them to proximity-related words. This condition was compared against the priming of neutral themes, positive affect, or attachment insecurity schemas. Then reports of empathy and personal distress or the accessibility of empathy and personal-distress memories were assessed. Attachment security priming strengthened empathic reactions and inhibited personal distress. Self-reports of attachment anxiety and avoidance were inversely related to empathy, and attachment anxiety was positively related to personal distress. The discussion emphasizes the relevance of attachment theory for explaining reactions to others' needs. PMID- 11761319 TI - Judgment under emotional certainty and uncertainty: the effects of specific emotions on information processing. AB - The authors argued that emotions characterized by certainty appraisals promote heuristic processing, whereas emotions characterized by uncertainty appraisals result in systematic processing. The 1st experiment demonstrated that the certainty associated with an emotion affects the certainty experienced in subsequent situations. The next 3 experiments investigated effects on processing of emotions associated with certainty and uncertainty. Compared with emotions associated with uncertainty, emotions associated with certainty resulted in greater reliance on the expertise of a source of a persuasive message in Experiment 2, more stereotyping in Experiment 3, and less attention to argument quality in Experiment 4. In contrast to previous theories linking valence and processing, these findings suggest that the certainty appraisal content of emotions is also important in determining whether people engage in systematic or heuristic processing. PMID- 11761320 TI - Mind at ease puts a smile on the face: psychophysiological evidence that processing facilitation elicits positive affect. AB - The affect system, in its position to monitor organismic-environmental transactions, may be sensitive to the internal dynamics of information processing. Hence, the authors predicted that facilitation of stimulus processing should elicit a brief, mild, positive affective response. In 2 studies, participants watched a series of neutral pictures while the processing ease was unobtrusively manipulated. Affective reactions were assessed with facial electromyography (EMG). In both studies, easy-to-process pictures elicited higher activity over the region of zygomaticus major, indicating positive affect. The EMG data were paralleled by self-reports of positive responses to the facilitated stimuli. The findings suggest a close link between processing dynamics and affect and may help understand several preference phenomena, including the mere-exposure effect. The findings also highlight a potential source of affective biases in social judgments. PMID- 11761321 TI - Organic redox cofactors. PMID- 11761322 TI - Substrates but not inhibitors alter the redox potentials of monoamine oxidases. AB - The midpoint potentials for the reduction of the cysteinyl-flavin adenine dinucleotide (FAD) in monoamine oxidases (MAO) A and B in the absence and presence of ligands have been determined. Both MAO A and MAO B can be reduced chemically in two steps, the first generating a semiquinone spectrum and the second the spectrum of fully reduced FAD, each of which requires two electron equivalents. The midpoint potentials for the oxidized/semiquinone and semiquinone/reduced couples were -159+/-4 mV and -262+/-3 mV for MAO A and -167+/ 4 mV and -275+/-3 mV for MAO B. After modification with a thiol reagent, direct reduction from the oxidized to fully reduced form was observed with no semiquinone and without change in the overall midpoint potential. In the presence of substrate, no semiquinone was formed, but the midpoint potential for full reduction of the flavin was positively shifted by up to 500 mV, depending on the substrate. This shift in potential could permit a more thermodynamically favorable transfer of electrons from the amine substrates to oxygen. In contrast, stable products and inhibitors did not cause a shift in potential and did not prevent the formation of semiquinone. PMID- 11761323 TI - Modulating the redox property of a flavin analog through adjustment of its microenvironment in a self-assembled monolayer. AB - Self-assembled monolayers (SAMs) have been used to examine the effects of electrostatic interactions and changing microenvironment on the pH-dependent redox properties of a flavin analog. The pKa value of the N1 proton for the reduced flavin analog was determined to be approximately 9.7 in the SAM of disulfide 5, 8.5 in the SAM of disulfide 7, and 6.7 when free in solution. The pyridinium ion of 7 stabilizes the anionic form of reduced flavin analog and provides a dielectric medium more closely resemblingthat experienced by the flavin analog free in solution. PMID- 11761324 TI - Further computational studies on the conformation of 1,5-dihydrolumiflavin. AB - The optimized geometry of 1,5-dihydrolumiflavin has been calculated using density functional theory (DFT). Reduced lumiflavin was found to be bent along the N5-N10 axis, 25 degrees from planarity, which is nearly the same as previously reported restricted Hartree-Fock (RHF) calculations, which predict a bending angle of 27 degrees. The major difference in the DFT calculation is that the N10 methyl group adopts a more pseudoequatorial disposition and is only bent 13 degrees above the plane of the isoalloxazine ring system as opposed to 59 degrees in the RHF calculations. These computational results are compared with x-ray crystal structures of flavin models and flavoproteins. DFT calculation of 1,5 dihydroisoalloxazine resulted in a more modestly bent geometry of 17 degrees. This indicates that both electronic and steric interactions of the N10 methyl group of reduced lumiflavin contribute to the bent geometry. PMID- 11761325 TI - Retro-nitroreductase, a putative evolutionary precursor to Enterobacter cloacae strain 96-3 nitroreductase. AB - Enterobacter cloacae strain 96-3 nitroreductase (NR) is a homodimeric flavoenzyme that catalyzes the pyridine nucleotide-dependent four-electron reduction of a variety of nitroaromatic compounds, including the explosives TNT (2,4,6 trinitrotoluene), RDX (1,3,5-trinitro-1,3,5-triazine), tetryl (2,4,6 trinitrophenyl-N-methylnitramine), and pentryl (2,4,6-trinitrophenyl-N nitroaminoethylnitrate). The enzyme was initially characterized by Bryant et al. from a strain of Enterobacter that had been isolated from a weapons dump in La Jolla, CA. The enzyme displays a catalytic efficiency for nitroreduction at least 10-fold higher than that of several highly homologous bacterial nitroreductases and has long been thought to have evolved to be a more efficient nitroreductase due to the high nitroaromatic compound concentrations in its environment. We report the cloning and biochemical characterization of a nitroreductase gene from a clinical isolate of Enterobacter cloacae, a strain that presumably had not encountered high concentrations of nitroaromatics. The new enzyme, which we term retro-nitroreductase, had an amino acid sequence 96.7% identical to NR, and most differences are relatively conservative. The catalytic efficiency of the new enzyme is twofold less than that of NR for the oxidation of NADH and is not significantly different from the value observed for NR for the reduction of dinitrobenzyl alcohol. We conclude that NR has not significantly evolved to be a more efficient nitroreductase as a result of its environment, and the relatively high catalytic activity of the enzyme is a general property of Enterobacter cloacae nitroreductases. PMID- 11761326 TI - Pyrroloquinoline quinone (PQQ) and quinoprotein enzymes. AB - This review summarises the characteristics, identification, and measurement of pyrroloquinoline quinone, the prosthetic group of bacterial quinoprotein dehydrogenases whose structures, mechanisms, and electron transport functions are described in detail. Type I alcohol dehydrogenase includes the "classic" methanol dehydrogenase; its x-ray structure and mechanism are discussed in detail. It is likely that its mechanism involves a direct hydride transfer rather than a mechanism involving a covalent adduct. The x-ray structure of a closely related ethanol dehydrogenase is also described. The type II alcohol dehydrogenase is a soluble quinohaemoprotein, having a C-terminal extension containing haem C, which provides an excellent opportunity for the study of intraprotein electron transfer processes. The type III alcohol dehydrogenase is similar but it has two additional subunits (one of which is a multihaem cytochrome c) bound in an unusual way to the periplasmic membrane. One type of glucose dehydrogenase is a soluble quinoprotein whose role in energy transduction is uncertain. Its x-ray structure (in the presence and absence of substrate) is described together with the detailed mechanism, which also involves a direct hydride transfer. The more widely distributed glucose dehydrogenases are integral membrane proteins, bound to the membrane by transmembrane helices at the N-terminus. PMID- 11761327 TI - Phototropins: a new family of flavin-binding blue light receptors in plants. AB - Phototropin is the designation originally assigned to a recently characterized chromoprotein that serves as a photoreceptor for phototropism. Phototropin is a light-activated autophosphorylating serine/threonine kinase that binds two flavin mononucleotide (FMN) molecules that function as blue light-absorbing chromophores. Each FMN molecule is bound in a rigid binding pocket within specialized PAS (PER-ARNT-SIM superfamily) domains, known as LOV (light, oxygen, or voltage) domains. This article reviews the detailed photobiological and biochemical characterization of the light-activated phosphorylation reaction of phototropin and follows the sequence of events leading to the cloning, sequencing, and characterization of the gene and the subsequent biochemical characterization of its encoded protein. It then considers recent biochemical and photochemical evidence that light activation of phototropin involves the formation of a cysteinyl adduct at the C(4a) position of the FMN chromophores. Adduct formation causes a major conformational change in the chromophores and a possible conformational change in the protein moiety as well. The review concludes with a brief discussion of the evidence for a second phototropin-like protein in Arabidopsis and rice. Possible roles for this photoreceptor are discussed. PMID- 11761328 TI - The covalent FAD of monoamine oxidase: structural and functional role and mechanism of the flavinylation reaction. AB - The family of flavoenzymes in which the flavin coenzyme redox cofactor is covalently attached to the protein through an amino acid side chain is covered in this review. Flavin-protein covalent linkages have been shown to exist through each of five known linkages: (a) 8alpha-N(3)-histidyl, (b) 8alpha-N(1)-histidyl, (c) 8alpha-S-cysteinyl, (d) 8alpha-O-tyrosyl, or (e) 6-S-cysteinyl with the flavin existing at either the flavin mononucleotide or flavin adenine dinucleotide (FAD) levels. This class of enzymes is widely distributed in diverse biological systems and catalyzes a variety of enzymatic reactions. Current knowledge on the mechanism of covalent flavin attachment is discussed based on studies on the 8alpha-S-cysteinylFAD of monoamine oxidases A and B, as well as studies on other flavoenzymes. The evidence supports an autocatalytic quinone methide mechanism of protein flavinylation. Proposals to explain the structural and mechanistic advantages of a covalent flavin linkage in flavoenzymes are presented. It is concluded that multiple factors are involved and include: (a) stabilization of the apoenzyme structure, (b) steric alignment of the cofactor in the active site to facilitate catalysis, and (c) modulation of the redox potential of the covalent flavin through electronic effects of 8alpha substitution. PMID- 11761329 TI - Catalytic control of redox reactivities of coenzyme analogs by metal ions. AB - Redox coenzymes and analogs have their own redox reactivities for both thermal and photochemical redox reactions. The redox activities of coenzymes can be tuned by using metal ions that can bind the redox coenzymes and analogs. Quantitative measure to determine the Lewis acidity of a variety of metal ions is given in relation to the catalytic reactivities. The mechanistic viability of metal ion catalysis in redox reactions of coenzyme analogs is described by showing a number of examples of both thermal and photochemical reactions that are made possible to proceed by controlling the redox reactivities of coenzymes with metal ions. PMID- 11761330 TI - Electronic structure studies of quinones and semiquinones: accurate calculation of spin densities and electron paramagnetic resonance parameters. AB - The application of electronic structure methods to the prediction of geometries, spin densities, and hyperfine couplings for biologically relevant quinones and semiquinones is reviewed. It is demonstrated that hybrid-type density functional methods are particularly suitable for such studies. Hydrogen bonding to the semiquinone oxygen by appropriate donors is shown to lead to a redistribution of spin density in the carbonyl group of the semiquinone. Experimental trends are well reproduced by the calculated values. Symmetric and asymmetric models of hydrogen bonding are modelled. It is shown that the symmetric models give good agreement with solution studies in vitro. The asymmetric models of hydrogen bonding give quite good agreement with values measured for in vivo semiquinones generated in the reaction centres of the purple photosynthetic bacterium, Rb sphaeroides, and also for the phyllosemiquinone free radical formed during electron transfer in Photosystem I of green plants. These recent advances in electronic structure calculations, in particular the applicability of density functional methods to the study of free radical properties, have opened up an exciting avenue for the complete characterisation of their electronic properties. In particular, the combination of experimental methods of electron paramagnetic resonance and such calculations should in future provide a clearer understanding of free radical chemistry in many areas of biology. PMID- 11761331 TI - Dissection of a flavoenzyme active site: the reaction catalyzed by cholesterol oxidase. AB - Cholesterol oxidase is a member of the glucose-methanol-choline (GMC) oxidoreductase family that is characterized by a conserved topology. We review our investigations into the reactivity of the Streptomyces cholesterol oxidase cofactor, flavin adenine dinucleotide (FAD), and the role of active-site residues. All of our mutagenesis, enzyme inhibition, and kinetic data demonstrate that the cofactor catalyzes oxidation of alcohols to ketones, but not oxygenation of carbon. Cholesterol oxidase catalyzes two reactions, oxidation and isomerization, in one active site, presumably because of the susceptibility of the reaction intermediate cholest-5-en-3-one to radical oxidation. This bifunctionality is not a shared characteristic with other GMC oxidoreductase family members. Furthermore, we have characterized the unusual inactivation of FAD by electrophilic substitution at C6 of the isoalloxazine ring upon ring opening of a cyclopropyl steroid. Another member of the GMC oxidoreductase family, methanol oxidase, is also inactivated by a cyclopropanol suggesting that inhibition by cyclopropanol inhibitors may be diagnostic of membership in this family. PMID- 11761332 TI - Advances in flavin and flavoprotein optical spectroscopy. AB - Flavins and flavoproteins are versatile redox cofactors that can perform both one and two-electron transfer. Because they are highly colored in all three oxidation states, optical spectroscopy has been exploited for decades to study these redox changes. This review summarizes the application of optical spectroscopies to flavins and flavoproteins since 1990. Special emphasis is placed on new techniques, such as Stark spectroscopy, as well as significant refinements in more well known techniques, such as resonance Raman spectroscopy and ultrafast spectroscopy. PMID- 11761333 TI - The FAD-PAS domain as a sensor for behavioral responses in Escherichia coli. AB - Aer, the aerotaxis receptor in Escherichia coli, is a member of a novel class of flavoproteins that act as redox sensors. The internal energy of the cell is coupled to the redox state of the electron transport system, and this status is sensed by Aer(FAD). This is a more versatile sensory response system than if E. coli sensed oxygen per se. Energy-depleting conditions that decrease electron transport also alter the redox state of the electron transport system. Aer responds by sending a signal to the flagellar motor to change direction. The output of other sensory systems that utilize redox sensors is more commonly transcriptional regulation than a behavioral response. Analysis in silico showed Aer to be part of a superfamily of PAS domain proteins that sense the intracellular environment. In Aer, FAD binds to the PAS domain. By using site specific mutagenesis, residues critical for FAD binding and sensory transduction were identified in the PAS domain. The PAS domain appears to interact with a linker region in the C-terminus. The linker region is a member of a HAMP domain family, which has signal transduction roles in other systems. PMID- 11761334 TI - Reduced flavin: donor and acceptor enzymes and mechanisms of channeling. AB - Although mechanisms of metabolite channeling have been extensively studied, the nature of reduced flavin transfer from donor to acceptor enzymes remains essentially unexplored. In this review, identities and properties of reduced flavin-producing enzymes (namely flavin reductases) and reduced flavin-requiring processes and enzymes are summarized. By using flavin reductase-luciferase enzyme couples from luminous bacteria, two types of reduced flavin channeling were observed involving the differential transfers of the reduced flavin cofactor and the reduced flavin product of reductase to luciferase. The exact mode of transfer is controlled by the specific makeup of the constituent enzymes within the reductase-luciferase couple. The plausible physiological significance of the monomer-dimer equilibrium of the NADPH-specific flavin reductase from Vibrio harveyi is also discussed. PMID- 11761335 TI - Artificial flavin receptors: effects of hydrogen bonding on redox properties of a flavin mimic. AB - This review describes the roles of hydrogen bonding on the redox properties of a flavin mimic by using artificial flavin receptors. The receptors exploited are melamine derivatives bearing guanidinium ion(s) that strongly bind 6-azaflavin through five or seven hydrogen bonds involving N(1), C(2)=O, N(3)-H, C(4)=O, N(5), and N(6) positions in CHCl3 and CHCl3-acetonitrile. It has been shown that receptors are quite useful for examination of the hydrogen bonding effects on the redox potential, stability of the anionic semiquinone radical, and the oxidation activity of 6-azaflavin. The functionalized receptors have a substrate- or a metal-binding site have been shown to facilitate the reactions by forming the noncovalent assemblies. A possibility as an apoprotein model of the receptors has been mentioned also. PMID- 11761336 TI - Effects of thiol antioxidants on hepatocyte growth factor signaling in cardiac myocytes. AB - We describe here novel antioxidant-sensitive events in which activation kinetics are delayed, leading to inhibition of cell signaling. Hepatocyte growth factor (HGF) transiently phosphorylated p44/42 mitogen-activated protein kinase (MAPK) with a peak at 3-5 min in HL-1 adult cardiac myocytes. Pretreatment of cells with thiol antioxidants, N-acetylcysteine or alpha-lipoic acid attenuated MAPK phosphorylation induced by a 3-min incubation with HGF. However, kinetic analysis revealed that the apparent inhibition of HGF signaling was due to a delay in the activation because HGF phosphorylated MAPK with a peak at 5-7 min in cells treated with thiol antioxidants. This 2-min delay in HGF activation of MAPK resulted in >5-min delay in phosphorylation of MAPK targets such as p90RSK and GATA-4. Hydrogen peroxide did not mimic HGF signaling, and HGF did not induce reactive oxygen species production. Thus, in cardiac myocytes, thiol antioxidants delay HGF-mediated MAPK activation and suppress subsequent signaling eventsvia reactive oxygen species-independent mechanism. PMID- 11761337 TI - Heparin-binding EGF-like growth factor decreases inducible nitric oxide synthase and nitric oxide production after intestinal ischemia/reperfusion injury. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to protect intestine from ischemia/reperfusion (I/R) injury in vivo and to down-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in intestinal epithelial cells in vitro. The present study was undertaken to investigate whether HB-EGF could modulate the iNOS/NO axis after total midgut I/R injury in rats. I/R injury induced a significant increase in iNOS gene expression (quantified by real-time RT-PCR) and protein production (detected by western blots), as well as elevation of serum NO levels (measured by chemiluminescence assay). Nitrotyrosine (NT) and iNOS production colocalized immunohistochemically, with positive staining found mainly in villous and crypt epithelial cells, as well as ganglion cells. Intraluminal administration of HB EGF 45 min after the start of a 90-min ischemic interval significantly decreased I/R-induced iNOS gene expression and protein production, as well as serum NO levels. Immunohistochemically, HB-EGF administration led to elimination of iNOS and NT staining in crypt epithelial cells and ganglion cells, with only weak staining that remained in villous epithelial cells. Thus, HB-EGF protects the intestine from I/R injury, at least partially, through down-regulation of the iNOS/NO/NT pathway, a mechanism that is central to I/R injury in multiple organ systems. PMID- 11761338 TI - The specific NOS2 inhibitor, 1400W, sensitizes HepG2 cells to genotoxic, oxidative, xenobiotic, and endoplasmic reticulum stresses. AB - We tested the hypothesis that the constitutive activity of the inducible form of nitric oxide synthase (NOS2) serves to protect cells against numerous endogenous stresses. To accomplish this, we treated HepG2 cell lines that were individually transfected with 13 different promoter/response element (RE) chloramphenicol acetyl transferase (CAT) reporter constructs, with a highly selective NOS2 inhibitor, 1400W [N-(3-(aminomethyl)benzyl) acetamidine)]. HepG2 cells were incubated for 6 h with 0, 1, 10, 50, 100, and 200 microM 1400W, and the activation of the promoter/RE CAT reporter constructs was simultaneously determined. The highest fold inductions occurred at 200 microM 1400W, a concentration that had no effect on overall cell viability, as determined by the MTT assay. Twelve of the 13 promoter/RE CAT reporter constructs were significantly activated by 200 microM 1400W. These results indicate the extensive protective role of constitutive NOS2 against genotoxic, oxidative, and endoplasmic reticulum stresses. The mechanism of this protection may involve the complexing of iron by nitric oxide (NO) to reduce hydroxyl radical formation, NO inhibition of electron transport and the generation of reactive oxygen species within mitochondria, NO inhibition of cyclooxygenase, lipoxygenase, and cytochrome P450 enzyme activity, and the scavenging of superoxide anions by NO to form peroxynitrite. PMID- 11761339 TI - The coming of age of behavioral research in physical activity. PMID- 11761340 TI - The transtheoretical model of behavior change: a meta-analysis of applications to physical activity and exercise. AB - The purpose of this study was to summarize findings from empirical applications of the transtheoretical model (TTM) (Prochaska & DiClemente, 1983) in the physical activity domain by using the quantitative method of meta-analysis. Ninety-one independent samples from 71 published reports were located that present empirical data on at least one core construct of the TTM applied to exercise and physical activity. In general, results support the application because core constructs differ across stages and most changes are in the direction predicted by the theory. Three general conclusions are offered. First, existing data are unable to confirm whether physical activity behavior change occurs in a series ofstages that are qualitatively different or along adjacent segments of an underlying continuum. Second, the growing number of studies that incorporate TTM concepts means that there is an increasing need to standardize and improve the reliability of measurement. Finally, the role ofprocesses of change needs reexamining because the higher order constructs are not apparent in the physical activity domain and stage-by-process interactions are not evident. There now are sufficient data to confirm that stage membership is associated with different levels of physical activity, self-efficacy, pros and cons, and processes of change. Further studies that simply stage participants or examine cross-sectional differences between core constructs of the TTM are of limited use. Future research should examine the moderators and mediators of stage transition. PMID- 11761341 TI - Effects of a physical activity intervention on body image in university seniors: project GRAD. AB - Project GRAD (Graduate Ready for Activity Daily) was a randomized controlled study to teach university seniors behavioral skills necessary for increasing and/or maintaining physical activity habits in preparation for the transition to working adult roles after graduation. This study examines the secondary effects of this intervention on body image concerns among college-aged men and women. Three hundred thirty-eight undergraduates (54%female, Mage = 24years, SD = 1.95; MBody Mass Index = 24.26, SD = 4.0) were studied. The sample was 61/% Anglo, 16% Latino, 16% Asian/Pacific Islander, 4% African American, and 3% Native American/Other Body image concerns were assessed at pre- and posttreatment using 2 subscales of the Eating Disorder Inventory: Drive for Thinness and Body Dissatisfaction. Because the latter concentrates on body parts typically associated with female concerns (e.g., thighs, hips, buttocks), a parallel scale was developed to target body parts that may be of more concern to men (e.g., legs, shoulders, arms, stomach). Results indicated that compared to the control group, women in the intervention showed a significant increase in drive for thinness without any changes in body dissatisfaction. For men, there were no significant changes in drive for thinness or body dissatisfaction. These results suggest that physical activity interventions may have some negative consequences of increasing concerns about thinness in women. This negative effect occurred despite intervention content designed to prevent concern over eating, dieting, and the importance of weight. Health promotion studies should include assessments of potential negative side effects. PMID- 11761342 TI - Agreement between participant-rated and compendium-coded intensity of daily activities in a triethnic sample of women ages 40 years and older. AB - Participant-rated and compendium-coded intensity of daily physical activities were compared in 148 African American, 144 Native American, 51 non-Hispanic White women ages 40 to 91 years who completed 4 days of activity records. For compendium-coded intensity, reported activities were classified as light (< 3 metabolic equivalents [METS]), moderate (3-6 METS), or vigorous (> 6 METS) using the Compendium of Physical Activities (1), whereas these categories were self assigned for participant-rated intensity. Minutes per day (min/d) spent in activities at each intensity level were computed. Relative to compendium-coded min/d, participants reported significantly greater time spent in light (+10 min/d; p < .01) and vigorous (+17 min/d; p < .001) activities, and less time spent in moderate activities (-27 min/d; p <.001). Similarly, compendium-coded estimates yielded higher rates ofparticipants meeting Centersfor Disease Control and Prevention-American College of Sports Medicine and Surgeon General recommendations than participant-rated estimates (11-18% differences) but substantially lower rates meeting American College of Sports Medicine vigorous recommendations (22% difference). Further, 247 greater kilocalories per day were estimated based on compendium-coded intensity. Kilocalories per day estimates based on compendium codings were more highly associated with pedometer counts than those based on participant ratings (p < .05). Studypatterns were generally seen across all sample subgroups. Discrepancies between participant and compendium estimates are likely to be most meaningful in studies estimating energy expenditure as it relates to health outcomes and in studies estimating vigorous activities. PMID- 11761343 TI - Framework PEACE: an organizational model for examining physical exercise across the cancer experience. AB - The primary purpose of this article is to provide a framework for organizing research on physical exercise and cancer control. A secondary purpose is to use this framework to provide an overview of the extant literature and to offer directions forr future research. The proposed framework, entitled Physical Exercise Across the Cancer Experience (PEACE), divides the cancer experience into 6 time periods: 2 prediagnosis (i.e., prescreening and screening/diagnosis) and 4 postdiagnosis (i.e., pretreatment, treatment, posttreatment, and resumption). Based on these time periods, 8 general cancer control outcomes are highlighted. Two cancer control outcomes occur prediagnosis (i.e., prevention and detection), and 6 occur postdiagnosis (i.e., buffering, coping, rehabilitation, health promotion, palliation, and survival). An overview of the physical exercise literature indicates that only I time period (i.e., prescreening) and cancer control outcome (i.e., prevention) has received significant research attention. Some time periods (i.e., treatment and resumption) and cancer control outcomes (i.e., coping and health promotion) have received modest research attention, whereas other time periods (i.e., screening/diagnosis, pretreatment, and posttreatment) and cancer control outcomes (i.e., detection, buffering, rehabilitation, palliation, and survival) have received only minimal attention. It is hoped that Framework PEACE will stimulate a more comprehensive and in-depth inquiry into the role of physical exercise in cancer control. PMID- 11761344 TI - Contributions of imagery ability to stress and relaxation. AB - This study examined the contribution of imagery ability to psychological and physiological responses to stress and relaxation. Individuals (N = 176) participated in two study sessions. In the first session, participants completed the Creative Imagination Scale and were block-randomized to a stress or relaxation condition based on imaging scores. During the second session, stress and mood were assessed before and after participants watched a stressful movie or listened to a relaxation tape. Finger temperature was monitored during the interventions. Changes in temperature and in self-reports of stress and mood indicated that the manipulations were effective. In comparison to low imagers, high imagers reported greater stress after the movie and less stress and negative affect after the relaxation tape. Imagery ability predicted neither levels of negative affect following the stress condition nor changes in positive affect or temperature during the interventions. In the stress condition, expectations of stress partially mediated the relation between imagery ability andpsychological stress. In contrast, expectations of relaxation did not significantly predict responses to the relaxation intervention. These findings suggest that imagery ability is related to greater subjective responses to both stress and relaxation and that, in stressful situations, expectancies may account for some of the effects of imagery ability on perceived stress. PMID- 11761345 TI - Biobehavioral responses to interpersonal conflict during anger expression among anger-in and anger-out men. AB - To examine whether typical modes of anger expression (ie., anger-in, anger-out) were related to cardiovascular, affective, behavioral, and cognitive responses to interpersonal conflict, 20 anger-in and 20 anger-out undergraduate men participated in 2 role plays, one in which they were instructed to exhibit their anger overtly and the other in which they inhibited their anger Results showed that anger-in individuals used significantly more repression self-statements than anger-out individuals across both role play interactions (p <.01). Anger-out persons showed exaggerated diastolic blood pressure response in contrast to anger in participants, but only during the exhibited anger role play (p <.04). When the anger exhibition role play followed anger inhibition, diastolic bloodpressure responses were more intense (p <. 05), and heart rate recovery was significantly slower (p <.03) among anger-outparticipants in contrast to anger-in participants. These findings indicate that modes of anger expression (trait) and contextual demands of the interaction (state) interact in complex ways to influence biobehavioral reactions to anger provocation. PMID- 11761346 TI - Predictors of improvement in a cognitive-behavioral intervention for women with rheumatoid arthritis. AB - In this article we present a secondary analysis of data from a brief cognitive behavioral intervention for women with rheumatoid arthritis that resulted in significant overall improvements in personal coping resources, pain coping behaviors, psychological well-being, and fatigue. Not every participant, however, improved during the intervention. Establishing predictors of improvement in brief interventions is important to optimize the cost-effective use of these resources. In search of predictors of improvement, we examined demographic and background variables, personal coping resources, pain coping behaviors, and social support. Both linear and quadratic effects were analyzed, comparing baseline measures to both immediate postintervention and 3-month follow-up outcomes using standardized indexes ofpredictors and criteria variables. After removing the effects of baseline scores on the outcomes index, significant predictors of improvement included length of time since diagnosis, personal coping resources, and maladaptive and adaptive pain coping behaviors. Both linear and quadratic effects were found, although this varied as a function of type of predictor. PMID- 11761347 TI - Anxiety and compliance among women at high risk for breast cancer. AB - The aim of this study was to investigate the association between symptoms of depression and general anxiety, patient's feelings of vulnerability to cancer, the anxiety experienced specifically in relation to various cancer screeningprocedures, and compliance with these procedures among women atfamilial risk for breast cancer The data were obtained from 430 patients from the High Risk Clinic at the UCLA Revlon Breast Center who completed the State-Trait Anxiety Inventory and answered questions about their perceived vulnerability to breast cancer; the anxiety they experienced regarding undergoing pap smear tests, mammograms, and breast self-examinations (BSEs); and their compliance with these cancer-screening procedures. Correlations were used to estimate the association between feelings of anxiety and compliance. We found that women attending programs targeting those at familial risk for breast cancer suffer from significant symptoms of general anxiety. General anxiety was found to be related to anxiety regarding specific screening practices but not to women's perceived vulnerability to cancer In general, neither general nor screening-specific anxiety were found to be related to patients 'compliance with screening practices; however, significant associations were found between patient's feelings of anxiety regarding BSEs and their actual performing them. BSE appears to be the only procedure for which compliance is negatively associated with procedure-specific anxiety. We offer possible explanations for this relation and discuss the possible psychological impact that recommendations regarding BSEs may have on highly anxious at-risk women. PMID- 11761348 TI - The relation between beliefs about drug treatments for HIV and sexual risk behavior in gay and bisexual men. AB - This study examined the relation between gay and bisexual men's (N = 575) beliefs about highly active antiretroviral therapy (HAART) and other HIV-related beliefs, intentions, and risk behaviors. Confirmatory factor analysis verified three belief factors: the extent to which HAART improves health among HIV-infected individuals, decreases the risk of HIV transmission, and is complicated and of limited efficacy. Men who endorsed the belief that HAART decreases HIV transmission risk expressed lower intentions to use condoms for anal sex and were more likely to have engaged in unprotected anal intercourse with a casual partner HIV-negative men who believed that HAART decreases transmission risk also perceived themselves to be more susceptible to HIV infection. Statistical evidence indicated that perceptions of susceptibility partially mediate the relation between sexual risk behavior and beliefs about HAART suggesting that beliefs may result from, rather than cause, increased risk behavior. PMID- 11761349 TI - Response bias influences mental health symptom reporting in patients with obstructive sleep apnea. AB - The Medical Outcomes Study (MOS) inventory is widely used to assess quality of life in chronically ill patients. Although response bias was addressed during its initial validation, we are unaware ofsubsequent studies examining how personality characteristics influence responses on this instrument. We examined the impact of response bias on MOS data reported by 44 obstructive sleep apnea (OSA) outpatients who completed the MOS and Marlowe-Crowne Social Desirability Scale (MC). Social desirability implies responding in a way that the participant believes will be viewed favorably; MC is often used to statistically controlfor this form of response bias on self-report measures. The MOS yielded 2 summary scales (Mental and Physical Health) and 8 dimensions (based on Short Form-36 [SF 36]). Data were analyzed using multiple regression analyses. Results show that there is a significant relation between MC and the Mental and Physical Health factors (R2 = .194, F = 5.069, p = .011) and the eight SF-36 dimensions (R2 = .359, F= 2.448, p = .032). Post hoc analyses did not reveal that any one independent variable was a superior predictor of the MC. Participants scoring high on the MC reported 31% greater health than participants scoring low on the MC. Findings suggest that response bias has a significant influence on MOS data from OSA patients, with the greatest impact on mental health indexes. Controlling for response bias on the MOS and other self-report measures is important in both research and clinical situations with OSA and potentially other chronically ill patients. PMID- 11761350 TI - Risk adjustment in the private sector. PMID- 11761351 TI - Why don't private employers use risk adjustment? Conference overview. PMID- 11761352 TI - The prevalence of formal risk adjustment in health plan purchasing. AB - This paper describes the prevalence of formal risk adjustment of payments made to health plans by Medicare, Medicaid, state governments, and private payers. In this paper, 'formal risk adjustment" is defined as the adjustment of premiums paid to health plans based on individual-level diagnostic or demographic information. We find that formal risk adjustment is used for about one-fifth of all enrollees in capitated health plans. While the Medicare and Medicaid programs rely on formal risk adjustment for virtually all their health plan enrollees, the practice is used for only about 1% of privately insured health plan enrollees. Ourfindings raise the question of why regulators have adopted formal risk adjustment, but private purchasers for the most part have not. PMID- 11761353 TI - Private employers don't need formal risk adjustment. AB - This paper lays down a set of hypotheses to explain why private employers do not use formal risk adjustment. The theme running through these hypotheses is simple: private employers don't need formal adjustment because they have better tools for dealing with adverse selection than formal risk adjustment provides. Open enrollment provisions, premium negotiations, and restricting employees' choices of health plans are mechanisms superior to formal risk adjustment for dealing with problems caused by adverse selection. PMID- 11761354 TI - Designing employer health benefits for a heterogeneous workforce: risk adjustment and its alternatives. AB - Many health economists recommend that employers provide employees with a risk adjusted choice among competing health insurance plans. However, formal risk adjustment is rarely if ever used by employers. This paper examines a range of health benefit design options available to employers, focusing attention not only on risk adjustment but also on its alternatives. We argue that while formal risk adjustment is rare, employers commonly use strategies that accomplish some of the same objectives at less cost. PMID- 11761355 TI - A demand-side view of risk adjustment. AB - This paper analyzes the efficient allocation of consumers to health plans. Specifically, we address the question of why employers that offer multiple health plans often make larger contributions to the premiums of the high-cost plans. Our perspective is that the subsidy for high-cost plans represents a form of demand side risk adjustment that improves efficiency. Without such subsidies (and in the absence of formal risk adjustment), too few employees would choose the high-cost plans preferred by high-risk workers. We test the theory by estimating a model of the employer premium subsidy, using data from a survey of large public employers in 1994. Our empirical analysis shows that employers are more likely to subsidize high-cost plans when the benefits of risk adjustment are greater. The findings suggest that the premium subsidy can accomplish some of the benefits of formal risk adjustment. PMID- 11761356 TI - Health plans and selection: formal risk adjustment vs. market design and contracts. AB - In this paper, we explore the demand for risk adjustment by health plans that contract with private employers by considering the conditions under which plans might value risk adjustment. Three factors reduce the value of risk adjustment from the plans' point of view. First, only a relatively small segment of privately insured Americans face a choice of competing health plans. Second, health plans share much of their insurance risk with payers, providers, and reinsurers. Third, de facto experience rating that occurs during the premium negotiation process and management of coverage appear to substitute for risk adjustment. While the current environment has not generated much demand for risk adjustment, we reflect on its future potential. PMID- 11761357 TI - Formal risk adjustment by private employers. AB - This paper explores explanations for why few private employers have adopted formal risk adjustment. The lack of data, challenges of using highly imperfect signals, and absence of market power are not compelling explanations. Alternative strategies that reduce selection problems are clearly important. The central argument is that U.S. health markets are not in equilibrium, but rather are changing rapidly. Since many agents-consumers, employers, health plans, and providers--do not currently demand formal risk adjustment, it is not surprising that adoption has been slow. Recent changes in health plan markets may change the demand and accelerate future adoption. PMID- 11761358 TI - Individual-based risk adjustment by health insurers: needs, options, and methods. PMID- 11761359 TI - Some observations about risk adjustment research. PMID- 11761360 TI - Location, race, and hospital care for AIDS patients: an analysis of 10 states. AB - This study is the first statewide comparison of hospital utilization and inpatient mortality rates for people with acquired immune deficiency syndrome (AIDS). Data from 120,772 hospital discharge abstracts for all AIDS-related admissions in 10 states (California, Colorado, Florida, Iowa, Kansas, Maryland, New Jersey, New York, Pennsylvania, and South Carolina) in 1996 were combined with data on the number and the racial and ethnic characteristics of all people living with AIDS (PLWAs) in each state. These data were used to derive population based estimates of the use of hospital services per PLWA and of inpatient mortality rates in each state. Multivariate analyses examined sources of variation in inpatient length of stay and inpatient mortality. The primary finding of this study is that hospital utilization rates and inpatient mortality rates for people with AIDS vary substantially across states and among racial and ethnic groups within states even after adjusting for severity of illness. Blacks and Hispanics had longer hospital stays and were more likely to die in the hospital than whites. State-level policies, such as home and community-based waiver programs and enhanced HIV reimbursement rates, significantly affected hospital use. PMID- 11761361 TI - Low-wage workers and health insurance coverage: can policymakers target them through their employers? AB - Many policy initiatives to increase health insurance coverage would subsidize employers to offer coverage or subsidize employees to participate in their employers' health plans. Using data from the 1997 Robert Wood Johnson Foundation Employer Health Insurance Survey, we contrast "low-wage employers" with all other employers. Employees in low-wage businesses have significantly worse access to employment-based insurance than other employees do; they are less likely to work for an employer that offers insurance, less likely to be eligible if working in a business that offers insurance, and less likely to be enrolled if eligible. Low wage employers contribute lower shares of premiums and offer less generous benefits than other employers do. Policies that would target subsidies to selected employers to increase insurance offers to low-wage workers are difficult to design, however, because several commonly mentioned employer characteristics (including firm size) are found to be poor indicators of low-wage worker concentration. Programs that would set minimum standards for employer plans to be eligible for "buy-ins" need to base these standards on the less generous terms offered by low-wage employers in order to effectively reach low-wage workers and their dependents. PMID- 11761362 TI - Development of a PCR test for the detection of Curtobacterium flaccumfaciens pv. flaccumfaciens. AB - A chromosomal DNA library of the bacterial pathogen of bean, Curtobacterium flaccumfaciens pv.flaccumfaciens NCPPB 559 was constructed in the plasmid pGEM 7Zf(+). Several clones were identified that hybridised to all Curtobacterium flaccumfaciens pathovars including: C. f betae, C. f flaccumfaciens, C. f oortii, C. f. poinsettiae and, in addition, to some strains of Clavibacter michiganensis subsp. insidiosus and Clavibacter michiganensis subsp. One of these clones (pPMP 26), after subsequent digestion with restriction endonucleases EcoRI/SacI, yielded a fragment of approximately 0.2 Kb (pPMP-26D) that hybridised specifically to C. f flaccumfaciens and not to any of the other plant pathogenic members of the order Actinomycetales or any of the other prokaryotic bean pathogens tested. This fragment was subcloned and sequenced, analysis of the resultant 198 bp sequence showed that no significant homology existed with any other sequence currently deposited in public databases. Further analysis of these data facilitated the design of PCR primers which were subsequently tested against a wide range of plant pathogenic actinomycetes and other prokaryotic bean pathogens. Results show that these primers are highly specific for all strains of C. f flaccumfaciens with no cross-reaction to strains from any other bacterial taxa tested. PMID- 11761363 TI - Human acylphosphatase cannot replace phosphoglycerate kinase in Saccharomyces cerevisiae. AB - Human acylphosphatase (h-AP, EC 3.6.1.7) has been reported to catalyse the hydrolysis of the 1-phosphate group of 1,3-diphosphoglycerate. In vivo operation of this reaction in the yeast Saccharomyces cerevisiae would bypass phosphoglycerate kinase and thus reduce the ATP yield from glycolysis. To investigate whether h-AP can indeed replace the S. cerevisiae phosphoglycerate kinase, a multi-copy plasmid carrying the h-AP gene under control of the yeast TDH3 promoter was introduced into a pgk1 delta mutant of S. cerevisiae. A strain carrying the expression vector without the h-AP cassette was used as a reference. For both strains, steady-state carbon- and energy-limited chemostat cultures were obtained at a dilution rate of 0.10 h(-1) on a medium containing a mixture of glucose and ethanol (15% and 85% on a carbon basis, respectively). Although the h AP strain exhibited a high acylphosphatase activity in cell extracts, switching to glucose as sole carbon and energy source resulted in a complete arrest of glucose consumption and growth. The lack of a functional glycolytic pathway was further evident from the absence of ethanol formation in the presence of excess glucose in the culture. As h-AP cannot replace yeast phosphoglycerate kinase in vivo, the enzyme is not a useful tool to modify the ATP yield of glycolysis in S. cerevisiae. PMID- 11761364 TI - Modular organization of the AIDA autotransporter translocator: the N-terminal beta1-domain is surface-exposed and stabilizes the transmembrane beta2-domain. AB - The adhesin involved in diffuse adherence (AIDA-I) of the diarrhoeagenic Escherichia coli strain 2787 (O126:H27) is synthesized as a precursor molecule. This pre-pro-protein is N- and C-terminally processed to generate three distinct domains, which are characteristic for autotransporter secretion systems in Gram negative bacteria: the N-terminal pre-peptide, the alpha-domain and the C terminal beta-domain. The outer membrane-integrated beta-domain (AIDAC) is responsible for the surface-presentation of the alpha-domain (AIDA-I) and is thus termed 'translocator'. Characterization of extracted N-terminally truncated forms and of in vitro refolded proteins revealed a core structure at the C-terminus of the translocator which was found to be very stable even in the presence of SDS. Denaturation occurs only after additional incubation at temperatures above 80 degrees C. Reporter-epitope insertions were used to analyze the location of regions of membrane-integrated AIDAC relative to the membrane. The modified topological model developed for the AIDA translocator suggests the N-terminal domain (beta1) encompasses approximately 10 kDa to represent a completely surface exposed segment while the C-terminal compact core domain (beta2) remains integrated in the membrane as a beta-barrel-like structure. Though the beta2-core structure alone harbours all the information for the outer membrane integration of AIDAC it is additionally stabilized by the beta1-domain. Access to large amounts of complete as well as truncated AIDAC proteins facilitated the study of protein folding by CD and fluorescence spectroscopy. A potential pore forming activity of the translocator using the completely refolded AIDAC or the beta2 core in black-lipid membranes could not be demonstrated. PMID- 11761365 TI - Study of murine faecal microflora by cellular fatty acid analysis; effect of age and mouse strain. AB - Analysis of bacteria-derived cellular fatty acids was applied to study differences in faecal floras of inbred mice. The bacterial composition of the faecal flora clearly changes with age, whereas the sex does not affect it. Most interestingly, different mouse strains were found to have different faecal floras. This was particularly observed at the age of 17-19 weeks for stool samples of four different mouse strains; the mice were handled identically in identical environments, and the two congenic strains used were different from each other only by the major histocompatibility complex (MHC). These results suggest that composition of the faecal flora is genetically regulated. PMID- 11761366 TI - Tilletiopsis derxii, Tilletiopsis oryzicola and Tilletiopsis penniseti, three new species of the ustilagionomycetous anamorphic genus Tilletiopsis isolated from leaves in Thailand. AB - Four strains of ballistoconidium-forming yeast-like fungi (K-95, K-125, K-132 and K139), isolated from plants collected in Bangkok, Thailand, were assigned to the genus Tilletiopsis based on morphological and chemotaxonomical characteristics. On the basis of sequence data of 18S rDNA and the D1/D2 region of 26S rDNA, strains K-95, K-125 and K-132 were close to T. flava and T fulvescens, and strain K-139 each formed related to T. minor. DNA-DNA reassociation experiments with related species revealed that strains K-125, K-132 and K-139 each formed a new and distinct species whereas strain K-95 was identified as T. flava. Tilletiopsis derxii Takashima et Nakase sp. nov. (JCM 10217T; K-125), Tilletiopsis oryzicola Takashima et Nakase sp. nov. (JCM 10218T; K-132), and Tilletiopsis penniseti Takashima et Nakase sp. nov. (JCM 1021 6T; K- 139) are the names proposed for the new taxa. PMID- 11761368 TI - Molecular characterization of Acidithiobacillus ferrooxidans and A. thiooxidans strains isolated from mine wastes in Brazil. AB - Nineteen strains of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans, including 12 strains isolated from coal, copper, gold and uranium mines in Brazil, strains isolated from similar sources in other countries and the type strains of the two species were characterized together with the type strain of A. caldus by using a combination of molecular systematic methods, namely ribotyping, BOX- and ERIC-PCR and DNA-DNA hybridization assays. Data derived from the molecular fingerprinting analyses showed that the tested strains encompassed a high degree of genetic variability. Two of the Brazilian A. ferrooxidans organisms (strains SSP and PCE) isolated from acid coal mine waste and uranium mine effluent, respectively, and A. thiooxidans strain DAMS, isolated from uranium mine effluent, were the most genetically divergent organisms. The DNA-DNA hybridization data did not support the allocation of Acidithiobacillus strain SSP to the A. ferrooxidans genomic species, as it shared only just over 40% DNA relatedness with the type strain of the species. Acidithiobacillus strain SSP was not clearly related to A. ferrooxidans in the 16S rDNA tree. PMID- 11761367 TI - Rapid flow cytometry--Nile red assessment of PHA cellular content and heterogeneity in cultures of Pseudomonas aeruginosa 47T2 (NCIB 40044) grown in waste frying oil. AB - The accumulation of cytoplasmic polyhydroxyalkanoates (PHAs) and the heterogeneity ofbacterial populations were analysed by flow cytometry and SYTO-13 and Nile red staining in rhamnolipid-producing Pseudomonas aeruginosa cultures grown in waste frying oil as carbon source. A combination of SYTO-13 and Nile red fluorescence with cytometric forward and side scatter values may allow increases in the final production of polyhydroxyalkanoates (PHA) by two basic mechanisms: (i) rapid assessment of polyhydroxyalkanoate content and (ii) definition of flow cytometric cell sorting protocols to select high polyhydroxyalkanoate (PHA) producing strains. We report a rapid (less than 30 min) flow cytometric assessment of PHAs in Pseudomonas aeruginosa 47T2 following Nile red staining: (i) to estimate cellular PHAs content; (ii) to study heterogeneity of the batch cultures producing PHAs and (iii) to establish the basis for sorting sub populations with a high capacity to accumulate PHAs. PMID- 11761369 TI - Two new anamorphic yeasts: Candida germanica and Candida neerlandica. AB - Descriptions are given for the two new anamorphic ascomycetous yeasts Candida germanica (type strain NRRL Y-27064, CBS 4105) and Candida neerlandica (type strain NRRL Y-27057, CBS 434). The species were isolated, respectively, from the atmosphere over Germany and from pressed yeast cake in The Netherlands. Phylogenetic analysis of 26S domain D1/D2 ribosomal DNA sequences places C. germanica near Pichia philogaea, whereas C. neerlandica is a member of the Lodderomyces elongisporus/Candida albicans clade. PMID- 11761370 TI - Molecular characterisation of Hanseniaspora species. AB - The sequences of the internal transcribed spacers (ITS regions) and the 5.8S rRNA gene, together with the electrophoretic karyotypes of 27 strains representative of the six species belonging to the genus Hanseniaspora, were examined. From the analysis of the 5.8S rRNA gene and the ITS regions, the genus Hanseniaspora is monophyletic and can be divided into two subgroups. This subdivision was supported by electrophoretic chromosome patterns. Hanseniaspora guilliermondii, H. uvarum and H. valbyensis show 6-7 bands (8 to 9 chromosomes), while the second group comprises the species H. occidentalis, H. osmophila and H. vineae which have only 5 chromosomes. PMID- 11761371 TI - Bioprospecting for novel oxylipins in fungi: the presence of 3-hydroxy oxylipins in Pilobolus. AB - As previously found in various members of the Mucorales, 3-hydroxy oxylipins in Mucor genevensis are associated with the sporangia, i.e. mainly the columella structure and between aggregating sporangiospores. To determine if this phenomenon is also true in distantly related members, the mucoralean fungus Pilobolus was examined. This fungus is characterized by relatively large sub sporangial-columella structures which actively eject sporangia in a sticky liquid for attachment onto herbage surrounding its growth medium--in this case horse dung. Strikingly, this fungus produced a novel oxylipin i.e. a 3-hydroxy monounsaturated fatty acid, possibly a nonenoic acid, which is mainly associated with the sub sporangial-columella structure and aggregating sporangiospores. The specificity of the antibody against 3-hydroxy oxylipins used in immunofluorescence mapping of the mucoralean fungi, was further confirmed in the yeast, Saccharomycopsis malanga which produces 3-hydroxy palmitate in crystal form. These crystals occur between aggregating yeast cells. On the basis of the available data, we hypothesize that 3-hydroxy oxylipins probably function as adhesives, attaching fungal cells to each other or to other surfaces through entropic based hydrophobic forces and/or hydrogen bonds. PMID- 11761372 TI - Are bats really involved in dengue virus transmission? PMID- 11761373 TI - Discovery, distribution, and abundance of the newly introduced mosquito Ochlerotatus japonicus (Diptera: Culicidae) in Connecticut, USA. AB - The earliest documented specimen of an exotic east Asian mosquito Ochlerotatus (Finlaya) japonicis japonicus (Theobald) in the Western Hemisphere is reported along with the results of a state wide survey to determine the distribution and abundance of this mosquito in Connecticut. Ochlerotatus japonicus was collected from 87 locations in eight counties. It is established throughout the state and occurs in a variety of natural and artificial container habitats including discarded tire casings, bird baths, wooden barrels, porcelain bath tubs (used for watering animals), plastic milk cartons, toys, vinyl tarpaulins (covering wood piles and swimming pools), exposed rock holes in stream beds, tree holes, subterranean catch basins, surface water rain pools, and spring-fed depressions. Larvae were particularly common in containers with water, decaying leaves, and algae, in shaded and sunlit areas and, in rock-pool habitats along streambeds, in association with Ochlerotatus atropalpus (Coquillett). Adult females were collected in sod grass-infused gravid and CO2- baited light traps, from early June through October, with peak collections in September. Biting females were collected by human bait method augmented with CO2, verifying its capacity to feed on humans. The ovitraps used in this study were not effective for recovering this species. Our results suggest that Oc. japonicus was introduced into Connecticut between 1992 and 1998. Because of the ability of Oc. japonicus to transmit West Nile virus, and because of the recent detection of this virus in field-collected specimens, the introduction of Oc. japonicus is considered a significant public health development. PMID- 11761374 TI - Histochemical localization of esterases in the integument of the female Boophilus microplus (Acari: Ixodidae) tick. AB - The cattle tick Boophilus microplus (Canestrini) is one of the most important ectoparasites affecting tropical cattle with worldwide distribution. Application of organophosphate compounds (OP) is extensively used as a tick control method. However, the appearance of ticks resistant to the OP decreases the therapeutic efficacy of such compounds. Esterases have been implicated as potential biochemical mechanisms for detoxification in B. microplus larvae. We found increased esterase activity in the inner layers of the integument of OP resistant adult female B. microplus ticks as compared with the OP susceptible ticks. We discuss the potential role of these enzymes during acaricide metabolism and propose future research. PMID- 11761375 TI - Lutzomyia pseudolongipalpis: the first new species within the longipalpis (Diptera: Psychodidae: Phlebotominae) complex from La Rinconada, Curarigua, Lara State, Venezuela. AB - Lutzomyia pseudolongipalpis, the first new sand fly species within the longipalpis complex, is described based on females and males from La Rinconada, Curarigua, Lara State, Venezuela. Similar to Lutzomyia longipalpis sensu lato, females of the new species show spermathecae with 8-10 annulations and cibarial armature with 8-12 horizontal teeth. However, L. pseudolongipalpis females show conspicuous vertical cibarial teeth, large stipites and wing vein sections, round cerci, and short and broad valvifers that separate them from L. longipalpis s. l. females. L. pseudolongipalpis and L. longipalpis s. l. males are isomorphic, both having parameres with two curved setae on a simple tubercle. The analysis of morphometric characters and their diagnostic value is in progress. PMID- 11761376 TI - Tissue localization of overproduced esterases in the mosquito Culex pipiens (Diptera: Culicidae). AB - We have investigated the tissue distribution of overproduced esterases A (A1 and A2) and B (B1 and B2) in strains of Culex pipiens L. by immunocytochemistry. S LAB mosquitoes, lacking overproduced esterases, were used as reference. Tissues showing a strong specific reaction (fluorescence) were observed with anti esterase A1 antiserum in S54 (with A1) and BOUAKE (with A2) strains, and with anti-esterase B1 antiserum in TEM-R and EDIT (with B1) and BOUAKE (with B2) strains. Overproduction of esterases A and B was tissue-specific. The most constant pattern for the two types of esterases was their overproduction in the alimentary canal and Malpighian tubes, although fluorescence varied in intensity depending on strains and developmental stages. There was no difference in the tissue distribution of esterases Al and A2. In contrast, esterases B pattern was highly variable among strains. Differences between TEM-R and EDIT were explained by the different overall overproduction and number of copies of the amplified gene (10-fold higher in TEM-R). The most striking difference in esterase B1 and B2 tissue localization concerned the nervous system where neurons were intenisely fluorescent in TEM-R and EDIT (B1), but not in BOUAKE (B2). All esterase B positive tissues in TEM-R contained large quantities of esterase B1 mRNA (in situ hybridization), indicating that at least part of the protein revealed by immunochemistry was produced in the tissues where it was observed. Our results are discussed in terms of the protection that the different esterases can confer during exposition to organophosphorous insecticides. PMID- 11761377 TI - Structures of the preantennal region of several species of Damalinia (Phthiraptera: Trichodectidae). AB - A comparative study was made of the structures of the preantennal region of nine species of Damalinia Mjoberg, 1910 (Phthiraptera: Trichodectidae). Variability in the form of the head, ventral carina, pulvinus, mandibles, and labrum was observed by light and scanning electron microscopy. According to previous studies, the form of the head is possibly influenced by the density and texture of the hair of the host. The ventral carina, which maybe sharp or blunt, and the pulvinus, a membranous lobe, of these parasite species of different hosts, were studied. Photographs of the mandibles and labrum show a high variability according to species. PMID- 11761378 TI - Stereochemical effects in an insect repellent. AB - Racemic 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine repels blood-feeding arthropods such as mosquitoes, chiggers, and ticks. The compound contains two asymmetric carbon atoms and the racemate consists of four stereoisomers. Quantitative mosquito bioassays using Aedes aegypti (L.) showed that (1S,2'S) and (1R,2'S) configurations were 2.8-3.1 and 1.6-1.8 times more effective, respectively, than the other two stereoisomers in reducing mosquito bites. (1S,2'S) was 2.5 more repellent than the racemate. Biological data show that an interaction of the (2'S)-2-methylpiperidine configuration with a repellent receptor system in A. aegypti is apparently important to repellent activity. Nuclear magnetic resonance spectra and molecular mechanics calculations for the stereoisomers provided insight into the conformation of the (2'S)-group. Results indicate that enhanced repellent effects can be realized through formulation of the most active stereoisomers of the compound. PMID- 11761379 TI - Spatial dispersion of adult mosquitoes (Diptera: Culicidae) in a sylvatic focus of Venezuelan equine encephalitis virus. AB - We studied the spatial localization of mosquitoes in sylvatic focus of Venezuelan equine encephalitis virus in western Venezuela to identify mosquito species potentially involved in the hypothesized transport of viruses out of enzootic foci. The following criteria were used to identify species with potential for virus export: (1) common in the forest and surrounding area, (2) feeding on a wide range of vertebrates; (3) long dispersal capabilities, and (4) established vectorial competence for enzootic or epizootic VEE viruses. CDC traps baited with light/CO2 were operated for four and 12-h intervals to collect mosquitoes at four stations along two forest/open area transects from September to November 1997. We collected 60,444 mosquitoes belonging to 11 genera and 34 species. The most common species were Aedes serratus (Theobald), Ae. scapularis (Rondani), Ae. fulvus (Wiedmann), Culex nigripalus Theobald, Cx, (Culex) "sp", Cx. mollis Dyar & Knab, Cx. spissipes (Theobald), Cx. pedroi Sirivanakarn and Belkin, Psorophora ferox (Humboldt), Ps. albipes (Theobald), and Ps. cingulata (F.). Very few mosquitoes were captured during the (day in the open area outside the forest, suggesting that any virus export from the forest may occur at night. The following mosquitoes seemed to be mostly restricted to the forest habitat: Ae. serratus, Ps. ferox, Ps. albipes, sabethines, Cx. spissipes, Cx. pedroi, Cx. dunni Dyar, and Ae. fulvus. The main species implicated its potential virus export were Cx. nigripalpus, Ae. scapularis, and Mansonia titillans (Walker). PMID- 11761380 TI - Effect of passive zooprophylaxis on malaria transmission in The Gambia. AB - The effect of zooprophylaxis on malaria transmission has not been studied on the African continent despite that the World Health Organization has recommended this intervention method since 1982. The effect of passive zooprophylaxis on malaria vector abundance, mosquito feeding preferences, and infectivity was studied in an area of moderate seasonal transmission in The Gambia. A paired cohort of 204 children <7 yr of age was selected and matched in groups for presence or absence of cattle (Bos taurus) within 20 m of their bedroom. Comparisons were made between mosquitoes collected from the bedrooms of the two groups of children. Other ruminants and equines were present in both groups of compounds. Most of the anopheline mosquitoes (98.5%) collected were Anopheles gambiae sensu lato. There was no difference in the geometric mean number of An. gambiae s.l. mosquitoes caught in houses near or far from cattle. The species composition of the An. gambiae complex was similar in both groups. Blood meal analysis of specimens collected in houses without cattle showed a human blood index (HBI) of 82% for An. Arabiensis (Patton), 56% for An. gambiae sensu stricto (Giles), and 36% for Anopheles Melas (Theobald), indicating that each of these sibling species fed readily on animals. The presence of cattle reduced the HBI of An. arabiensis but did not significantly alter the HBI of An. gambiae s.s. or An. melas. There was no significant difference between the groups in the sporozoite rates of An. gambiae s.l. nor in the estimated malaria transmission risk. These findings suggest that passive zooprophylaxis using cattle does not alter the individual exposure to malaria parasites in The Gambia. PMID- 11761381 TI - Movement of Rhodnius prolixus (Hemiptera: Reduviidae) within a simulated house environment. AB - We observed the movement, attraction, and resting behavior of laboratory Rhodnius prolixus Stal within a house environment, simulated by a Styrofoam box. Movement of R. prolixus into various refuge types (fiberpots or white-, cream-, or black colored modified Gomez-Nunez boxes) at different strata was assessed. Greater numbers of fifth instars sought a refuge than third instars. Fasted nymphs sought a refuge more than fed nymphs. Our simulated house environment showed potential as a laboratory arena to observe the resting preferences, dispersal, and response of kissing bugs to potential attractants. Our data indicated that fiberpot refuges may serve as an effective and inexpensive monitoring device to detect low density kissing bug infestations. PMID- 11761382 TI - Electron microscopic observations on wound-healing in larvae of the mosquito Armigeres subalbatus (Diptera: Culicidae). AB - The wound-healing processes in the mosquito Armigeres subalbatus (Coquillett) were observed with electron microscopy. The initial reaction involved wound contractions and aggregation of injured surface tissues, cell debris and movement of granulocytes toward the wound. Granulocytes first aggregated around the surface of the wound and many filamentous filopodia protruded to connect with cytoplasmic strands. These strands were then interconnected to form a network coagulum resulting in wound closure to prevent body fluid loss. Granulocytes lysed on the wound-site and released granular materials around the wound, inducing localized clot formation. These results suggested that wound-healing in this mosquito species involved both humoral and cellular reactions. The latter reaction involved the movement of plasmatocytes to the basement membrane of the epidermis beneath the wound-site and epithelial cells regeneration. Our observations revealed that wound-healing in A. subalbatus involves the wound contraction, formation of a temporary cellular clump, scar formation, basement membrane formation, and reepithelialization. The larvae neither discarded the wound scar nor secreted a new cuticle until the next molting. Based on the ultrastructural observations, it is suggested that the wound-healing reaction in A. subalbatus was probably a typical response employed by other members of the family Culicidae. PMID- 11761383 TI - A novel technique for removing Wolbachia infections from Aedes albopictus (Diptera: Culicidae). AB - Intracellular bacteria of the genus Wolbachia often behave as reproductive parasites by manipulating host reproduction to enhance the vertical transmission of infections. Wolbachia infections in Aedes albopictus (Skuse) cause a reproductive manipulation known as cytoplasmic incompatibility, which can reduce brood hatch. Because field populations of Ae. albopictus are naturally infected, studies of Wolbachia-induced effects on Ae. albopictus reproduction and fitness require that Wolbachia be artificially removed. Although simiple techniques for clearing Wolbachia infections from other host insects have been developed, removal of Wolbachia bacteria from Ae. abopictus is difficult. Here we describe an improved method for removing Wolbachia infections Ae. albopictus. This method differs from earlier techniques in that it relies upon the tetracycline treatment of adults instead of larvae. We demonstrate that tetracycline treatment of adult Ae. albopictus can predictably generate uninfected individuals, simplify the procedure required for Wolbachia removal, and reduce the level of inbreeding required to produce uninfected lines. PMID- 11761384 TI - Invasion: exotic ticks (Acari: Argasidae, Ixodidae) imported into the United States. A review and new records. AB - A review of the literature and unpublished records from the U.S. National Tick Collection on the importation of ticks from foreign lands reveals that at least 99 exotic tick species assignable to 11 genera have been either detected and destroyed at ports of entry or inadvertently imported into the United States in the past half century. This number includes four argasid and 95 ixodid species, some of which are important vectors of agents that cause disease to both man and animals. If one includes Aponomma sp. and Hyalomma sp. and the subspecies of Rhipicephalus, the total exceeds 100 taxa. It is notable that the number of imported tick species recorded herein exceeds the total number of tick species native to the United States. It appears that the soft tick genera Argas, Antricola and Nothoaspis have not been imported, although at some point in time Argas persicus (Oken) was introduced because it is resident although not often collected. The hard tick genera Anomalohimalaya, Cosmiomma, Margaropus, Nosomma and Rhipicentor, and the nuttalliellid genus Nuttalliella have also not been imported. PMID- 11761385 TI - The status of Linshcosteus in the Triatominae (Hemiptera: Reduviidae). AB - Of the 17 genera in Triatominae, only one, Linshcosteus, occurs exclusively outside the New World (India). Its relationship to the rest of the subfamily has been questioned, a question made urgent by the fact that many triatomines are vectors of the protozoan which causes Chagas' disease. Using a simple measure of similarity, we show that Linshcosteus is less similar to the other triatomine genera than each of them is to the others. PMID- 11761386 TI - Innate preference for host-odor blends modulates degree of anthropophagy of Anopheles gambiae sensu lato (Diptera: Culicidae). AB - In field studies, Anopheles gambiae Giles sensu stricto obtains most blood meals from humans, whereas Anopheles quadriannulatus Theobald bites predominantly bovids. We investigated whether host odors modulate the host preference of these mosquito species. In a dual-choice olfactometer, mosquitoes were given a choice between clean air and putative host-specific odor blends. An. gambiae chose 'human odor' over clean air and clean air over cow odor.' Although Anopheles quadriannulatus did not choose cow odor over clean air, it chose clean air over human odor. Cheese odor, which attracted An. gambiae, did not result in higher trap catch of An. quadriannulatus. We conclude that the degree of anthropophagy of An. gambiae s.l. has an innate olfactory basis. PMID- 11761387 TI - Enhanced pulmonary expression of endothelin-1 in an ovine model of smoke inhalation injury. AB - Recent studies suggest a role of endothelin-1 (ET-1) in mediating airway inflammation and lung injury. The aim of this study was to assess the immunohistochemical expression of ET-1 in the lung following smoke inhalation injury. ET-1 immunoreactivity was assessed in normal sheep (N = 4) and in sheep at 1 (N = 2), 6 (N = 3), 12 (N = 3), and 24 (N = 3) hours after inhalation injury. In normal animals, ET-1 expression was limited to the basal cell layer of the tracheal epithelium, main bronchi, and associated mucous glands. One hour after injury, ET-1 immunoreactivity was enhanced in upper airway epithelium and mucus glands with new expression in bronchioles. Airway smooth muscle, vascular tissue, and alveolar duct smooth muscle cells expressed moderate levels of ET-1 at 12 and 24 hours. ET-1 immunoreactivity was absent in areas of parenchymal edema and inflammation. The pattern of ET-1 expression following inhalation injury suggests that this peptide may contribute to the airway inflammation, mucus secretion, pulmonary hypertension, increased airway resistance, and decreased lung compliance, which are evident in our ovine model of inhalation injury. PMID- 11761388 TI - Marjolin's ulcers arising in burn scars. AB - Epidermoid carcinoma in nonhealing scar tissue, known as Marjolin's ulcer, is not uncommon and is thought to behave in a more aggressive fashion than those from other causes. Between 1982 and 1997, 56 patients with Marjolin's ulcer were treated at our center, Ege University Medical School, Izmir, Turkey. All lesions were secondary to various kinds of burns. Forty of these patients could be followed up 5 years or more. These 40 patients' medical records were reviewed retrospectively. PMID- 11761389 TI - Prospective trial of thick vs standard split-thickness skin grafts in burns of the hand. AB - For best function and appearance, thick skin grafts for hands are generally preferred to thinner grafts. But how thick is thick enough? This prospective randomized trial was designed to compare 0.015-inch skin grafts for burned hands to hand grafts that are 0.025 inches thick. Consecutive patients receiving skin grafts to hands were randomized to have sheet grafts using donor sites of 0.015 inch or 0.025-inch thickness. To prevent delayed healing and potential hypertrophic scarring, the thick graft donor sites were grafted with 0.008-inch grafts. There were no significant differences in range of motion, final appearance, or patient satisfaction between the two groups at 1 year. There were problems with donor site healing in both groups. We recommend that hand grafts for adults be at least 0.015 inches thick but do not see an advantage to the use of very thick (0.025-inch) grafts, even with thin split-thickness skin grafts to the donor site. PMID- 11761390 TI - Storage media and temperature maintain normal anatomy of cadaveric human skin for transplantation to full-thickness skin wounds. AB - Cadaveric human skin provides an optimal temporary cover after early excision of full-thickness burns; however, engraftment is reduced greatly by cryopreservation. Refrigerated skin is generally preferred because of its rapid revascularization, presumably caused by its greater viability. In this study, the effects of storage solutions, temperature, and the changing of the storage media on skin graft anatomy were evaluated as an indicator of graft viability. Split thickness human skin grafts (0.012-0.015 mm) were retrieved from cadaveric donors and grafted to circumferential, full-thickness skin wounds on athymic mice. After clinical determination of engraftment 3 months after grafting, 6-mm punch biopsy samples of the human skin were harvested and separated into two groups. Biopsy samples were stored in either saline or Eagle's minimal essential medium. Media were not changed or were changed every 3 days. All groups were stored at either 4 degrees C or room temperature (RT). After 5, 10, and 21 days of storage, biopsy samples were grafted onto athymic mice for 20 days. The biopsy grafts were then collected and prepared for histologic scoring on a scale of +4 (normal anatomy) to 0 (no epithelial cells). Significant differences in histologic scores were found by the nonparametric Kruskal-Wallis test followed by Wilcoxon pairwise comparison. Skin stored in media maintained better histologic anatomy than skin in saline, suggesting better maintenance of viability. There was also better preservation of anatomy after storage at RT for 21 days with media changes every 3 days when compared to unchanged media and all conditions at 4 degrees C. These results support the hypothesis that increased availability of nutrients and increased storage temperature maintain higher viability of cadaveric human skin for transplantation to full-thickness cutaneous wounds. PMID- 11761391 TI - Dexter: a tool to facilitate impairment ratings. AB - Calculating impairment in burn patients is crucial to understanding outcome. However, it is rarely reported after burns, presumably because the process of calculating impairment ratings is complicated and tedious. Computerized systems have been developed that facilitate the process, but it has not been established in burn patients that these systems reduce the time required to calculate impairment. We evaluated the Dexter Evaluation and Therapy System by Cedaron Medical Inc (Davis, CA). A sample of 10 manually recorded ratings was compared with 10 performed on the Dexter. Mean time for the manual technique was 65 +/- 35 minutes versus 37 +/- 13 minutes for the Dexter (P < .05, Mann-Whitney). The time taken to perform impairment ratings in burn survivors is significantly reduced by the use of the Dexter system. Time saving occurs primarily at three points: (1) electronic data entry directly from the measuring instruments, (2) compilation of data, and (3) rapid generation of reports. PMID- 11761392 TI - Time off work and return to work rates after burns: systematic review of the literature and a large two-center series. AB - The literature on time off work and return to work after burns is incomplete. This study addresses this and includes a systematic literature review and two center series. The literature was searched from 1966 through October 2000. Two center data were collected on 363 adults employed outside of the home at injury. Data on employment, general demographics, and burn demographics were collected. The literature search found only 10 manuscripts with objective data, with a mean time off work of 10 weeks and %TBSA as the most important predictor of time off work. The mean time off work for those who returned to work by 24 months was 17 weeks and correlated with %TBSA. The probability of returning to work was reduced by a psychiatric history and extremity burns and was inversely related to %TBSA. In the two-center study, 66% and 90% of survivors had returned to work at 6 and 24 months post-burn. However, in the University of Washington subset of the data, only 37% had returned to the same job with the same employer without accommodations at 24 months, indicating that job disruption is considerable. The impact of burns on work is significant. PMID- 11761393 TI - Microvascular assessment of burn depth conversion during varying resuscitation conditions. AB - Conversion of partial- to full-thickness injuries, even after the burning has stopped, remains a significant clinical problem. We developed a rat model with a wide range of burn depths to study this phenomenon by microvascular assessment. Fifty-four male Sprague-Dawley rats weighing 460 g on average were studied. Real time tissue monitoring of pH, paCO2, and paO2 was achieved by placement of a continuous blood gas monitor transducer in the aorta. Ten, 2-cm x 2-cm burns were created on each animal with milled aluminum templates (100 degrees C) with varying contact times. Conversion of burn depth in these wounds was documented by serial laser Doppler imager scanning over a 5-hour period. Animals received Ringer's lactate resuscitation at 0, 2, 4, 6, and 8 ml/kg/%burn. Serial laser Doppler scanning directly demonstrated progressive loss of perfusion to partial thickness burns dependent upon the amount of fluid resuscitation. Conversion of partial- to full-thickness burns in this rat model (documented by laser Doppler microvascular assessment) was dependent upon how the animals were resuscitated. PMID- 11761394 TI - Rates, trends, and severity of depression after burn injuries. AB - It is commonly assumed that patients hospitalized for burn treatment will experience some level of depression. However, little is known about the trends in severity of depression over time. The purpose of this study was to determine the rates and severity of depression over a 2-year period. The Beck Depression Inventory was administered at 1 month (N = 151), 1 year (N = 130), and 2 years (N = 125) after discharge. At 1 month, 54% of patients showed symptoms of moderate to severe depression, and at 2 years, 43% of the patients responding still reported moderate to severe depression. The average correlation between scores over time was high. Women had higher depression scores than men at each time period. An interaction between gender and having a head or neck injury was also observed at 1 month and 1 year after discharge. Results suggest that routine outpatient screening for depression is warranted. PMID- 11761395 TI - Computer-Related activities at the 2001 ABA annual meeting. PMID- 11761396 TI - Major burn injuries among restaurant workers in New York City: an underappreciated public health hazard. AB - Major burns among food service workers appears to be an underappreciated source of morbidity and public expense in New York City. A retrospective study was conducted to identify workers requiring hospital admission over the past 3 years. Seventy-six restaurant workers (3.8% of all adult admissions) were identified. They averaged 33 years of age, and sustained burns with a mean %TBSA of 12.5, resulting in a mean length of stay of 12.8 days. Scalds predominated, with water/coffee burns most common (n = 29), followed by oil (n = 27), and soup/sauce burns (n = 12). Burns to the extremities occurred in 97% of patients. Surgery was required in 32 of 76 patients (42.1%). Oil burns were more likely to require surgery than aqueous scalds (59 vs 34%; P < 0.01). Hospitalization expenses averaged $1.13 million dollars per year. There were no mortalities. Restaurant related major burns are a frequent occurrence, particularly scald injuries. Hospital care and further disability result in enormous publicly funded expenses. The morbidity and lost wages are a severe detriment to workers and their families. Greater public health awareness measures are warranted. PMID- 11761397 TI - Use of resources for illegal immigrants. PMID- 11761398 TI - Duration of dysphagic symptoms and swallowing outcomes after thermal burn injury. AB - Levels of swallowing disability, patterns of dysphagia rehabilitation and swallowing outcomes on discharge were retrospectively reviewed for 30 patients with thermal burn injury (with or without inhalation injury), referred to speech pathology services for dysphagia management. The average total surface burn area of the group was 50%. All patients were mechanically ventilated for an average of 24 days, with 80% of patients requiring subsequent tracheostomy. Initial dysphagia assessment occurred approximately 20 days after admission, whereas first safe oral intake was achieved by approximately 30 days. Supplementary nutrition and hydration was necessary for all patients. The time to achieve oral intake without supplementation was 53 days. Outcome measures revealed a significant improvement in swallowing function throughout the duration of inpatient stay, with 90% of patients discharged safely tolerating a normal diet, 6.7% of patients managing soft diet consistencies, and 3.3% managing soft puree consistencies on discharge. PMID- 11761399 TI - A new splinting approach for dorsal foot burns. AB - Successful treatment of dorsal foot burns is a challenge. By extrapolating from various treatments of dorsal hand burns the design of a static progressive splint was applied to the treatment of dorsal foot burns to prevent contracture deformities. The splint is composed of a base, dorsal thermoplastic piece, and Velcro strap. Soft hook and loop Velcro encircles the ankle and midfoot providing a base for the attachment of a Velcro strap. A thermoplastic piece is conformed to the dorsum of the toes and then affixed to the Velcro strap. The Velcro strap is then attached to the plantar surface of the base to create an adjustable static progressive stretch. This splint is designed to prevent dorsal foot contractures during the scar maturation phase of wound healing. PMID- 11761400 TI - Origin and distribution of sulphate in surface waters of the Mansfeld mining district (Central Germany)--a sulphur isotope study. AB - In the Mansfeld region (Central Germany) copper mining contributed to an enormous pollution of the environment. Metal- and sulphate-bearing sediments and leachates emerge from the former copper smelters and mining waste heaps, spread along local rivers and finally reach the Saale river. A sulphur isotope study on water and stream sediments was performed along the River "Bose Sieben" and from its tributaries to determine the different sulphur sources. Four major sulphur sources exist in the area: metal sulphide mineralisations (Kupferschiefer), met alliferous sulphidic flue dust, slag, and anhydrite and gypsum of Permian and Triassic age. We obtained delta34S(SO4)-values in water samples varying from +4 per thousand to -18 per thousand CDT, clearly reflecting the input of sulphate from different sources. Sulphate from the oxidation of sulphidic mining residues is restricted to the mining area and cannot be traced for more than 5 km downstream. The major source for sulphate is the dissolution of gypsum and anhydrite. The sulphur isotope composition in dissolved and sedimentary adsorbed sulphate differs only slightly from each other. Microbial dissimilatory sulphate reduction can not be excluded in the shallow sediment layers. PMID- 11761401 TI - Terrigenous clay deposition on estuarine sandflats: using stable isotopes to determine the role of the mud crab, Helice crassa Dana, in the recovery process. AB - Clay slurries, mixed in seawater, were deposited on intertidal mudflats in two contrasting estuaries in an experiment designed to evaluate the potential impact of soil erosion from adjacent urban developments on the biodiversity of the benthic communities, and the subsequent recovery mechanisms. Profiles of the natural abundance of stable isotopes from sediment cores where examined to determine immediate and longer-term impacts of the clay on the ambient sediments. The source clays with delta13C values of about -26 per thousand were easily distinguished from natural sediments with delta13C values of -19.7 +/- 1.1 per thousand at site OK and -14.2 +/- 0.9 per thousand at site WP, and bioturbation was seen to generate a gradient between these values. Physical processes of burial, or erosion and dispersal by estuarine flows initiated the recovery process. Repeated drying cycles left the clay surface cracked and able to trap natural sediments and food on the otherwise barren surface. Colonisation of the clay plots by the mud crab, Helice crassa, was important to the recovery process and depended on proximity to adjacent crab colonies. Burrowing activity by larger crabs enhanced the erosion of the clay surface while the resultant bioturbation blended the clay into the underlying sediments. Smaller crabs had less effect on erosion and bioturbation from their burrowing was mostly confined within the clay layer. Where the clay was more than 3 cm thick, they did not break through the bottom of the clay and the interface between clay and sediment was still sharp after 12 months. 13C variations also indicated that crab burrows and cracking of the clay surface moved natural sediment deep into the plots where it could be worked into the clay by subsequent crab burrowing activities thus enhancing recovery from the clay impact. PMID- 11761402 TI - Influences of heterotrophic and autotrophic resource use on carbon and hydrogen isotopic compositions of tropical tree leaves. AB - The delta13C and SD values of newly emerging to senescing tree leaves produced during a rainy season were obtained in dry seasonal and moist forest in Panama. Newly emerging leaves had less negative delta13C values than older leaves yet instantaneous pi/pa was never lowest in the youngest leaves. Furthermore, isotopic enrichment during early growth may have a detectable influence on the delta13C values of mature leaves. The deltaD values of cellulose nitrate were only related to deltaD values of leaf water if leaf age was also considered so that, for a given deltaD of leaf water, deltaD values were highest in the youngest leaves (R2 = 98%). There was no correlation between leaf age and deltaD values of leaf water. Investment of translocated organic carbon is a factor likely to be associated with both 13C and deuterium enrichment effects in new leaves. A coarse, mass balance approach can estimate the proportional heterotrophic investment in leaf growth and improve estimates of integrated pi/pa by approximating delta13C for the most autotrophic phase of leaf growth. Delta13C values of the predominantly sucrose mobile organic fraction in new leaves were less negative than in older leaves, thereby suggesting that the enrichment did not occur at the original site of production of the substrate for new leaf growth. Although the delta values of early leaf growth must be influenced by inputs of translocated organic carbon, enrichment effects, per se, are apparently caused by other mechanisms such as, for carbon, de novo sucrose synthesis and anaplerotic replenishment. Better recognition of metabolic causes of isotopic enrichment in leaves promises to increase the power and accuracy of inferences about carbon and water use of tropical trees from delta analyses. PMID- 11761403 TI - Delta13C and deltaD values of Opuntia atacamensis depending on different environmental conditions in the Atacama desert of Northern Chile. AB - We analysed 13carbon and deuterium discrimination in Opuntia atacamensis PHIL. at three different sites in the Atacama desert in Northern Chile: At the western Andean slopes, influenced by summer rainfall, in the very arid Chilean central valley, and at coastal fog mountains. At the most arid site, the central valley, discrimination of 13C and D was less (delta-values less negative) and also discrimination more against deuterium. This is an aridity, not an altitude effect. The differences in 13C content may be due to some carbon fixation via the C3 photosynthetic pathway at the more humid sites. Deuterium enrichment at the arid sites might be due to greater discrimination of HDO against H2O during transpirational water loss. PMID- 11761404 TI - The [15N]methacetin liver function test characterizes multicomponent exposure of children in industrially polluted regions. AB - The [15N]methacetin urine test for assessing disturbances of the cytochrome P450 aided oxygenation of xenobiotics in the human liver has been approved in several environmental health studies. A recent longitudinal study of kindergarten children near chemical and mining companies undergoing fundamental restructuring showed high, seasonally fluctuating SO2 burden which was well correlated with alterations in the mean liver states of the children. At one point the correlation disappeared, together with indications of large amounts of chlorinated compounds overflowing locally at nighttime. This was finally proven by analyzing urine samples from the children for trichloroacetic acid (TCA). Chlorinated ethanes and ethenes-the precursors of TCA-seemed to dominate the air pollution and to affect the hepatic detoxification capacity. We concluded that the methacetin liver function test reflects multicomponent exposure, including acute monopolization by a dominant pollutant for a time. PMID- 11761405 TI - The position dependent 15N enrichment of nitrous oxide in the stratosphere. AB - The position dependent 15N fractionation of nitrous oxide (N2O), which cannot be obtained from mass spectrometric analysis on molecular N2O itself, can be determined with high precision using isotope ratio mass spectrometry on the NO+ fragment that is formed on electron impact in the source of an isotope ratio mass spectrometer. Laboratory UV photolysis experiments show that strong position dependent 15N fractionations occur in the photolysis of N2O in the stratosphere, its major atmospheric sink. Measurements on the isotopic composition of stratospheric N2O indeed confirm the presence of strong isotope enrichments, in particular the difference in the fractionation constants for 15N14NO and 14N15NO. The absolute magnitudes of the fractionation constants found in the stratosphere are much smaller, however, than those found in the lab experiments, demonstrating the importance of dynamical and also additional chemical processes like the reaction of N2O with O(1D). PMID- 11761406 TI - Sulfur isotope fractionation in the biogeochemical sulfur cycle of marine sediments. PMID- 11761407 TI - Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias. AB - INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. METHODS AND RESULTS: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in approximately 11% of the Japanese population. This 1727G>A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in approximately 30% reduction in the slow delayed rectifier K+ current I(Ks) without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. CONCLUSION: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I(Ks) dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population. PMID- 11761408 TI - Single nucleotide polymorphisms and life-threatening arrhythmias: causal or casual? PMID- 11761409 TI - Relation between body surface mapping and endocardial spread of ventricular activation in postinfarction heart. AB - INTRODUCTION: Body surface mapping (BSM) can be used to identify the site of earliest endocardial activation of ventricular tachycardias (VTs). The multielectrode QRS morphology during VT is determined by both the site of earliest activation and the subsequent spread of electrical activation through the ventricles. This study investigated the relationship between the site of earliest endocardial activation, endocardial spread of activation, and the morphology of the multielectrode surface map in patients with remote myocardial infarction. METHODS AND RESULTS: In 14 patients with VT late (8.2+/-5.2 years) after myocardial infarction, BSM and simultaneous left ventricular 64-site basket endocardial mapping was performed during a total of 17 monomorphic VTs. In addition, multisite pacing by sequential use of the 64 basket electrodes was performed in 9 patients. BSM and basket mapping revealed the same endocardial breakthrough sites in 8 (47%) of 17 VTs and 189 (59%) of 322 pacing sites; adjacent sites were found in 2 (12%) of 17 VTs and 36 (11%) of 322 pacing sites. Large zones of conduction block explained the mismatch in localization in 2 (12%) of 17 VTs and 52 (16%) of 322 pacing sites. Regional differences in endocardial electrogram amplitudes were found as a cause for dissimilarity in 3 (18%) of 17 VTs and 73 (23%) of 322 pacing sites. Multiple endocardial breakthrough sites were found in 1 (6%) of 17 VTs and 8 (2%) of 322 pacing sites Finally, an epicardial exit site was suggested in 3 (18%) of 17 VTs as an explanation for mismatch, as no early endocardial activity could be recorded. CONCLUSION: Zones of conduction block, regional differences in signal amplitude, and multiple endocardial breakthrough sites are frequent causes for mismatch between BSM and basket catheter activation mapping. PMID- 11761410 TI - Hyperventilation facilitates induction of supraventricular tachycardia: a novel method and the possible mechanism. AB - INTRODUCTION: Hyperventilation has been demonstrated to alter autonomic function. Sympathomimetic drugs (isoproterenol) and parasympatholytic drugs (atropine) may be needed to facilitate induction of supraventricular tachycardia (SVT). The aim of this study was to test the clinical utility and mechanisms of hyperventilation to facilitate SVT initiation. METHODS AND RESULTS: Fourteen patients with clinically documented SVT (9 AV nodal reentrant tachycardia and 5 AV reciprocating tachycardia) but noninducible during baseline electrophysiologic study were included. Immediately after hyperventilation test (at least 30 respirations/min) for 2 minutes, systolic blood pressure, sinus cycle length, anterograde and retrograde 1:1 conduction, and induced SVT were measured. Arterial blood gas, pH, and heart rate variability before and after hyperventilation were measured. Seven of nine patients with AV nodal reentrant tachycardia and 3 of 5 patients with AV reciprocating tachycardia could be induced immediately after the hyperventilation test. After hyperventilation, anterograde AV and retrograde VA 1:1 conduction were improved, sinus cycle length was decreased, and heart rate variability were decreased in both groups. CONCLUSION: Hyperventilation can facilitate induction of SVT. Improvement of conduction properties and changes of autonomic function are the possible mechanisms. PMID- 11761411 TI - Clinical experience with a dual-chamber implantable cardioverter defibrillator to treat atrial tachyarrhythmias. AB - INTRODUCTION: This study evaluated the safety and efficacy of a new dual-chamber implantable cardioverter defibrillator (ICD) to detect and treat atrial tachyarrhythmias in patients with drug-refractory atrial fibrillation (AF) and no indication for a ventricular ICD. METHODS AND RESULTS: A dual-chamber ICD (Medtronic 7250 Jewel AF) was implanted in 144 of 146 patients. The device discriminates atrial tachycardia from AF based on cycle length and regularity, and uses atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 12.6+/-6.2 months. Use of antiarrhythmic drugs was 63% at baseline and did not change over time. Kaplan Meier estimates of 12-month complication-free survival, device therapy survival, and patient survival were 85%, 91%, and 98%, respectively. Positive predictive accuracy of spontaneous atrial tachyarrhythmia detection was 99%, while atrial overdrive pacing and shocks terminated 40% and 87% of treated episodes, respectively. Median duration of successfully treated episodes was 8.9 minutes versus 144 minutes for the therapy failures. There was no reduction in the use of patient-activated shock therapy over time; at the 12-month follow-up evaluation, 94% of patients were in sinus rhythm. Ventricular tachyarrhythmias (67 episodes) were detected and appropriately treated in 7.6% of patients. CONCLUSION: This dual-chamber ICD appears to be safe and well tolerated in patients with drug refractory symptomatic atrial tachyarrhythmias. The device, used in combination with drugs, effectively treats atrial tachyarrhythmias with pacing and/or shock therapies and decreases the median episode duration. In addition, the device protects from ventricular tachyarrhythmias in patients with AF and structural heart disease. PMID- 11761412 TI - Implantable device therapy of atrial tachyarrhythmias: ready for prime time? PMID- 11761413 TI - Ventricular echo beats and retrograde atrioventricular nodal exits in the dog heart: multiplicity in their electrophysiologic and anatomic characteristics. AB - INTRODUCTION: A single ventricular echo beat frequently is induced in the dog heart by ventricular pacing, but it has not been investigated using a concomitant ablative technique. We studied the effects of ablating the anterior atrial input to the AV node on ventricular echo beats induced in the dog heart to evaluate their electrophysiologic characteristics, the anatomic reentrant circuit, and the retrograde AV nodal exits. METHODS AND RESULTS: In 20 dogs, an epicardial radiofrequency current was applied to the right anterior septum in an attempt to ablate the anterior input to the AV node. Ventricular programmed stimulation was performed to evaluate the ventricular echo beat and the retrograde AV nodal exit before and after ablation. The AV junction was examined with light microscopy. Seventeen dogs in which the PR interval was prolonged significantly from 108+/-17 msec to 153+/-19 msec (P < 0.001) were selected for ventricular echo evaluation; 3 dogs in which persistent second- or third-degree AV block was induced by ablation were excluded. Ventricular echo beats, which were induced in 13 of 17 dogs, were classified into the anterior type (n = 6) or posterior type (n = 7) according to the earliest atrial activation site during the echo beat. The retrograde AV nodal exit site showed anterior-exit only (n = 10), posterior-exit only (n = 2), and dual-exit (n = 5) patterns. After ablation, the anterior-type ventricular echo beat was noninducible in all 6 dogs, whereas the posterior-type ventricular echo beat was noninducible in only 3 of 7 dogs. In 17 dogs, VA conduction was not demonstrated after ablation in 3 dogs, all of which showed the anterior-exit only pattern. CONCLUSION: The effect of ablation on the ventricular echo beats and retrograde AV nodal exit site suggests multiplicity in their electrophysiologic and anatomic characteristics in the dog heart. PMID- 11761414 TI - Anatomic criteria for identifying the components of the axis responsible for atrioventricular conduction. PMID- 11761415 TI - Evolution of action potential propagation and repolarization in cultured neonatal rat ventricular myocytes. AB - INTRODUCTION: Cultured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providing a useful model for studying activation and repolarization. METHODS AND RESULTS: We used the multielectrode array data acquisition system with 60 unipolar electrodes to investigate the functional organization of cultured NRVM, by determining propagation and repolarization patterns. Activation maps were constructed from the local activation times at each electrode. During days 3 to 8 in culture, QRS amplitude and dV/dt(max) increased with age. Concomitantly, with the culture maturation, QT interval (representing action potential duration) decreased, and T wave amplitude and slopes of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogram properties, slightly increasing during the first 3 to 5 days and gradually declining toward day 8 in culture. CONCLUSION: Establishment of uniform activation patterns in spontaneously firing or driven myocytes in monolayer cultures is accompanied by organization of activation and repolarization whose evolution appears in concert with that of a mature connexin43 staining pattern. The experimental techniques developed in this study provide useful tools to investigate the complex relations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysiologic conditions predisposes the myocardium to arrhythmias. PMID- 11761416 TI - Feasibility of a left atrial electrical disconnection procedure for atrial fibrillation using transcatheter radiofrequency ablation. AB - INTRODUCTION: An effective, catheter-based treatment for persistent atrial fibrillation (AF) remains elusive. This study assessed the feasibility of transcatheter left atrial (LA) electrical disconnection and its effect on AF inducibility. METHOD AND RESULTS: Thirteen anesthetized swine underwent noncontact mapping of the right atrium (RA) during coronary sinus (CS) pacing. Sites of earliest RA activation were identified using isopotential maps. An ablation catheter was navigated to these sites and a cluster of radiofrequency (RF) lesions applied until earliest activation shifted to a new site. The procedure was repeated until the atria were electrically disconnected. AF induction was attempted before and after ablation. Earliest RA activation was the CS os during proximal CS pacing and Bachmann's bundle during distal CS pacing. These two sites were successfully ablated in all 13 animals. Earliest activation then shifted to the fossa ovalis. RF energy was applied at a median of 2.5 sites (range 1 to 5) around the fossa, then at sites in the triangle of Koch, septum, cavotricuspid isthmus, and posterior wall. Atrial electrical disconnection was achieved in 10 of 13 animals (5 LA electrical disconnection, 3 RA electrical disconnection, 2 biatrial electrical disconnection with complete heart block). After atrial electrical disconnection, the LA became electrically silent. Before ablation, AF was inducible in every animal. After atrial electrical disconnection, AF was inducible in 3 of 10 animals. CONCLUSION: Atrial electrical disconnection is feasible using noncontact mapping and RF ablation. Successful electrical disconnection of the atria reduces AF inducibility. This approach is worthy of further evaluation as a management strategy for persistent AF, combined with device therapies. PMID- 11761417 TI - When technology exceeds knowledge, is success a reasonable expectation? PMID- 11761418 TI - Monophasic action potential recordings from intact mouse heart: validation, regional heterogeneity, and relation to refractoriness. AB - INTRODUCTION: The monophasic action potential (MAP) technique has been validated in humans and larger animals, but, in mice, MAP recordings available to date show little resemblance to the murine ventricular transmembrane action potential (TAP) measured by conventional microelectrodes. We developed a miniaturized MAP contact electrode technique to establish in isolated mouse hearts: (1) optimal electrode size; (2) validation against TAP; (3) relationship between repolarization and refractoriness; and (4) regional repolarization differences. METHODS AND RESULTS: In 30 Langendorff-perfused mouse hearts, MAP electrodes of tip diameter 1.5, 1.0, and 0.25 mm were tested by comparing MAPs and TAPs from epicardial and endocardial surfaces of both ventricles. Only the MAP contact electrode of 0.25 mm tip diameter consistently produced MAP recordings that had wave shapes nearly identical to TAP recordings. MAP durations measured at 30%, 50%, 70%, and 90% repolarization (APD30, APD50, APD70, APD90) highly correlated with TAP measurements (r = 0.97, P < 0.00001). APD50 was significantly longer in endocardial than in epicardial recordings (right ventricle: 9.3+/-1.1 msec vs 3.9+/-1.1 msec; left ventricle: 9.9+/-2.1 msec vs 6.2+/-1.9 msec; both P < 0.001), demonstrating transmural repolarization differences. Effective refractory period (ERP) determined at basic cycle lengths from 70 to 200 msec correlated with 80%+/-6% of total repolarization, with an ERP/APD90 ratio of 0.85+/-0.14. CONCLUSION: Murine myocardial repolarization, regional repolarization heterogeneity, and relation to refractoriness can be assessed reliably by this miniaturized MAP contact electrode technique, which renders action potential wave shapes similar to that of intracellular microelectrodes. This technique may be useful for exploring repolarization abnormalities in genetically altered mice. PMID- 11761420 TI - Of mice and men: in vivo electrophysiologic testing in genetically engineered mice. PMID- 11761419 TI - In vivo electrophysiologic studies in endothelial nitric oxide synthase (eNOS) deficient mice. AB - INTRODUCTION: Endothelial nitric oxide synthase (eNOS) mediates attenuation of the L-type calcium channel and modulates myocyte contractility. Arrhythmogenic afterdepolarizations are seen in vitro in ouabain-treated isolated myocytes from eNOS-deficient mice. The aim of these studies was to characterize the baseline electrophysiologic (EP) phenotype of eNOS-deficient mice and their potential susceptibility to cardiac conduction abnormalities and inducible arrhythmias. METHODS AND RESULTS: Surface ECG and in vivo intracardiac EP studies were performed in 27 mice lacking the eNOS gene and 21 wild-type littermate control mice. Baseline studies were performed in 10 eNOS-deficient mice and 10 wild-type controls. Subsequently, 17 eNOS-deficient mice and 11 wild-type controls were pretreated with digoxin, and ECG and EP testing were repeated. Data analysis revealed no significant differences in ECG intervals or cardiac conduction parameters, except sinus cycle length was higher in eNOS-deficient mice than wild type mice (P < 0.01). After digoxin pretreatment, 7 of 17 eNOS-deficient mice had inducible ventricular tachycardia and 2 others had frequent ventricular premature beats, compared with only 3 of 11 wild-type mice with inducible ventricular tachycardia. In addition, 2 digoxin-treated eNOS-deficient mice and 1 wild-type mouse had inducible nonsustained atrial fibrillation. CONCLUSION: Mice with a homozygous targeted disruption of the eNOS gene have slower heart rates but no other distinguishable EP characteristics under basal sedated conditions. Partial inhibition of the Na+/K+ ATPase pump with digoxin administration increases ventricular ectopic activity in eNOS-/- mice, a phenotype analogous to afterdepolarizations seen in vitro in this eNOS-deficient mouse model. PMID- 11761421 TI - Benefit of pacing and beta-blockers in idiopathic repetitive polymorphic ventricular tachycardia. AB - An 18-year-old woman presented with recurrent exercise-induced syncopal episodes and severe systolic dysfunction. ECG monitoring disclosed repetitive polymorphic ventricular complexes, paroxysms of bidirectional ventricular tachycardia, and nonsustained bursts of slow polymorphic ventricular tachycardia that increased in length and rate during exercise. Ventricular arrhythmias were refractory to medical treatment, which included verapamil and beta-blockers. Addition of permanent atrial pacing to beta-blocker therapy suppressed the arrhythmias and reversed systolic impairment in the following months. PMID- 11761422 TI - A good case. PMID- 11761423 TI - Localization of the origin of arrhythmias for ablation: from Electrocardiography to advanced endocardial mapping systems. AB - Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra-atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter-based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter-based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed. PMID- 11761424 TI - The T wave: a window on ventricular repolarization? PMID- 11761425 TI - Supraventricular tachycardia with alternating cycle length: what is the mechanism? PMID- 11761426 TI - Cardiac arrest following carotid sinus massage. PMID- 11761427 TI - Pulmonary vein dilation in patients with atrial fibrillation: detection by magnetic resonance imaging. PMID- 11761428 TI - Molecular pathology of pituitary adenomas. AB - A great deal of knowledge about anterior pituitary development, the pathogenesis of pituitary tumor and pituitary tumor progression has accumulated during the past decade. The role of multiple genes and gene products in pituitary development and the relationship of these genes to postnatal pituitary function and pituitary tumor development are being actively explored. Recent studies indicate that genes important in pituitary development do not contribute to pituitary tumorigenesis. However, mutations and other genetic alterations in these genes often lead to pituitary hypofunction. Many oncogenes and tumor suppressor genes that contribute to pituitary tumorigenesis have been described. There is a growing body of evidence showing that cellular and molecular changes in cyclins and cyclin-dependent kinase inhibitors contribute to pituitary tumorigenesis. Finally, recent comparative genomic hybridization studies show that many more genes that are important in pituitary tumorigenesis and tumor progression have yet to be discovered. PMID- 11761429 TI - Classification of pituitary adenomas. AB - This brief review summarizes various schemes which were introduced to classify pituitary tumors of adenohypophysial origin. Many different classifications were proposed. Pathologists prefer classifications based on the morphologic features of tumor cells. The gold standard is the light microscopic study of hematoxylin eosin stained sections of formalin fixed and paraffin-embedded tissues. For correlation between hormone production, secretory activity and cytogenesis, immunohistochemical and transmission electron microscopic investigation is needed. We are convinced that in the future, molecular and genetic techniques will also be applied. We present here our five-tier scheme for classification of pituitary tumors which was accepted by the 'World Health Organization International Histological Classification of Tumours'. This classification takes into consideration the clinical and laboratory findings, imaging results, histologic, immunocytochemical and ultrastructural features of tumor cells. Despite several recent attempts to assess the growth rate, aggressiveness and invasiveness of pituitary tumors, more work is required to draw conclusions on their prognosis. PMID- 11761430 TI - Acromegaly: historical perspectives and current therapy. AB - Soon after the initial description of acromegaly in the late 19th century, neurosurgeons performed the first operative procedures for the disease. Transcranial procedures eventually yielded to the transsphenoidal approach. Reasonably effective medical therapy was introduced in the 1970s and pharmacological progress continues to be realized. It is now recognized that excess growth hormone is associated with significant morbidity and mortality and that biochemical remission improves outcome. Although medical and radiation treatments offer useful adjuncts, surgery provides optimal results. PMID- 11761431 TI - Current management of prolactinomas. AB - Prolactinomas constitute the largest group of pituitary adenomas in autopsy series. However, their relative incidence in recent surgical series is much less impressive since medical treatment with dopamine agonists is routinely employed, which in many cases leads to tumor shrinkage and normalization of prolactin levels. The clinical symptoms of hyperprolactinemia are menstrual dysfunction and galactorrhea in women and loss of libido and potency in men. Prolactinomas may present also as space occupying sellar mass lesions impinging on the adjacent structures like the pituitary gland, cavernous sinus and optic nerves. The standard primary treatment is medical by dopamine agonists. Prolactinomas are the prototype of tumors, the growth of which can be reliably and safely inhibited by specific drugs other than cytostatic chemotherapy. These unfortunately have side effects, like orthostatic hypotension, nausea and vomiting. The effects induced by dopamine agonists are suppressive but not tumoricidal. Thus, the therapeutic effect is only maintained as long as the drug is administered. Consequently. in most cases, treatment has to be continued life-long with a few exceptions, in whom normoprolactinemia persists even after discontinuation of dopamine agonists. Main indications of surgery in prolactinomas are intolerance of the medication, and tumors not responding to dopamine agonists. Occasionally, these may ultimately require radiation therapy. Remission rates in large series of surgically treated prolactinomas vary between 54% and 86%. In our consecutive series of 540 surgically treated prolactinomas, the normalization rate after transsphenoidal surgery basically depended on the preoperative prolactin levels, tumor size and extension. The remission rate of 82% in microprolactinomas with initial prolactin levels <200 ng/ml would even in small adenomas make one consider surgical treatment as an interesting alternative to long-term medical treatment. PMID- 11761433 TI - Endocrine inactive and gonadotroph adenomas: diagnosis and management. AB - Endocrine inactive pituitary adenomas represent about one quarter of all pituitary tumors. By immunocytochemistry, most of these tumors are positive for intact gonadotropins and/or their subunits. Clinical presentation is usually secondary to mass effect symptoms, such as visual disturbances, headache, and hypopituitarism. Differential diagnosis is usually accomplished by neuroradiologic studies, even though in selected cases positron emission tomography and/or single photon emission tomography may aid to distinguish pituitary adenomas from other endocrine inactive lesions, such as meningiomas and craniopharyngiomas. Surgical management is usually considered the first choice treatment for patients with endocrine inactive pituitary adenomas because it is very effective in ameliorating symptoms of chiasmal compression and headache. Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Radiation therapy diminishes the likelihood of tumor recurrence, especially in patients with demonstrable tumor remnants after surgery. Medical therapy with dopaminergic drugs, somatostatin analogs, or gonadotropin-releasing hormone agonists or antagonists causes mild reduction of tumor size in few patients and, therefore, seems to be of limited value in the therapeutic management of patients with endocrine inactive pituitary adenomas. PMID- 11761434 TI - Thyrotropin-secreting pituitary adenomas. Clinical and biological heterogeneity and current treatment. AB - Thyrotropin (TSH)-secreting pituitary adenomas represent about 1-2% of all pituitary adenomas and cause secondary or central hyperthyroidism. TSH-secreting adenomas are part of the syndrome of 'inappropriate secretion of TSH' (SITSH). The hormonal profile is characterized by nonsuppressed TSH in the presence of high levels of free thyroid hormones (FT3 and FT4). Previous reports have described the surgical cure of TSH adenoma to be more difficult than other functional adenomas because of large and invasive features. However, with the current introduction of ultrasensitive immunometric assays, TSH-secreting adenomas are more often recognized. Early diagnosis of TSH-secreting adenomas leads to a high rate of remission of hyperthyroidism after surgery. However, some of those type of adenomas have clinical heterogeneity, and subsequently cannot be cured by surgery alone. We present our experiences and review reported cases of TSH-secreting adenomas to direct current management. PMID- 11761432 TI - Cushing's disease: a surgical view. AB - The management of adrenocorticotropic hormone (ACTH)-dependent Cushing's disease implies difficulties in the differential diagnosis, in the detection of minute pituitary adenomas, as well as in the radical removal of invasive adenomas. Magnetic resonance imaging (MRI) is unspecific and often negative in minute adenomas of three or less millimeters diameter. The trias of detectable ACTH, suppression of cortisol in the high-dose dexamethasone test, and stimulation in the corticotropin-releasing-hormone (CRH)-test has a high accuracy to prove pituitary dependency. In unclear cases, the use of inferior petrosal sinus sampling (IPSS) or cavernous sinus sampling (CSS) for the exclusion of ectopic ACTH-syndrome is currently advised especially in cases where cranial MRI is negative. The reliability of these methods to localize the mostly lateralized microadenomas is still discussed. Transsphenoidal microsurgical adenomectomy, the accepted primary therapy of Cushing's disease, has been published from experienced pituitary centers with remission rates ranging from 70% to 98% in the last decade. False diagnosis (pseudo-Cushing, ectopic ACTH-syndrome), incorrect adenoma localization by IPSS or CSS, and the rate of minute or non-resectable invasive tumors influence the results. The handling of minute specimen implies problems for surgeon and pathologist. Intraoperative tumor localization was improved by ACTH measurement from the cavernous sinus and the adenoma itself, by cytology, and frozen sections. The histology of the anterior lobe (rate of Crooke's cells) bears information of clinical relevance. Invasive macroadenomas may deserve repeat microsurgery, medical treatment, and radiosurgery. PMID- 11761435 TI - Endoscopic transsphenoidal surgery. AB - BACKGROUND: Endoscopic transsphenoidal surgery was developed under a minimally invasive surgical strategy. This endonasal transsphenoidal endoscopy eliminates a sublabial or transfixional incision, the use of a transsphenoidal retractor and any nasal packing. MATERIALS AND METHOD: Reported are 160 patients who had undergone endoscopic transsphenoidal surgery from 1993 to 1999. Seventy were men and ninety women. Age ranged from 14 to 88 years (median 43 years). Among the 160 patients, 128 had pituitary adenomas, 9 had anterior fossa meningiomas, 7 had clival chordomas and 16 patients had other pathologies. RESULTS: Among the 68 patients with hormone-none-secreting adenomas, 53 (78%) patients had gross total removal. Among the 35 patients with prolactinomas, 24 (71%) patients exhibited normalized prolactin levels postoperatively. Eleven (70%) patients among the 16 with Cushing's disease had normal postoperative cortisol levels. Among the 9 patients with acromegaly, 7 (78%) had normalized postoperative IGF-1 levels. Among the 9 patients with anterior cranial fossa meningiomas. 7 had gross total removal and 2 had subtotal removal. Among the 7 patients with clival chordomas, 5 had total removal and 2 had subtotal removal. One patient with a large calcified recurrent pituitary fibrosarcoma died postoperatively. Postoperative morbidities included cerebrospinal fluid (CSF) leak in 6%, meningitis in 1.2%, deterioration of anterior pituitary function in 11%, temporary diabetes insipidus in 4%, permanent diabetes insipidus in 3%, and sinusitis in 1.2%. Outpatient surgery was performed in 2 patients. One hundred and eleven patients (66%) stayed in the hospital only overnight. Postoperative discomfort was minimal. CONCLUSION: Endoscopic endonasal transsphenoidal surgery in this series resulted with comparable surgical outcomes to conventional microscopic transsphenoidal surgery. Patients' quick recovery, short hospital stays, and minimal postoperative discomfort have been observed. PMID- 11761436 TI - The role of gamma knife radiosurgery in the management of pituitary adenomas. AB - No treatment modality has been entirely successful in the management of pituitary adenomas. Although most patients with pituitary microadenomas can be cured by transsphenoidal surgery, the results are less satisfactory in macroadenomas in particular with suprasellar and/or parasellar extension. Additional treatment is then called for. Conventional fractional radiotherapy can often control tumour growth but is limited to 45-50 Gy with a very slow reduction in elevated pituitary hormones and a high incidence of pituitary insufficiency. Stereotactic radiosurgery allows the delivery of radiation with high precision to the target with low doses to the surrounding tissues permitting higher radiation doses. Gamma knife radiosurgery using photon energy with gamma beams from multiple cobalt 60 radiation sources is now used in many centers. It can be carried out in an outpatient setting with one single treatment. A more rapid normalization of pituitary hormone hypersecretion than with conventional radiation can be achieved as well as arrest of tumour growth and reduction of tumour mass. We therefore consider gamma knife radiosurgery as a valuable compliment to pituitary surgery. Long-term prospective studies are needed to evaluate the frequency of pituitary insufficiency in patients where the target area is determined with stereotactic magnetic resonance imaging (MRI). PMID- 11761438 TI - Treatment of human colon carcinoma cell lines with anti-neoplastic agents enhances their lytic sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes. AB - Certain anti-neoplastic agents at subtoxic doses may exert immunomodulatory effects, which alter the expression of specific tumor cell surface molecules. We reasoned that potential increases in tumor cell surface markers, such as those important for facilitating effector-target contact, as well as triggering cell death pathways, might then improve antigen (Ag)-specific T-cell-mediated tumor cytolysis. Here, in a human colon carcinoma cell model in vitro, we examined whether the anti-neoplastic agents 5-fluorouracil (5-FU), CPT-11 or cisplatin (CDDP) could upregulate the expression of specific tumor cell surface markers, which may then enhance productive lytic interactions between CD8+ CTL and Ag bearing tumor cells. Based on our earlier studies, IFN-gamma treatment was included as a control for sensitization to CTL-mediated lysis. Pretreatment of the SW480 primary colon carcinoma cell line with IFN-gamma, 5-FU, CPT-11 or CDDP enhanced ICAM-1 and Fas expression, resulting in Ag-specific CTL-mediated lysis involving Fas-dependent and -independent mechanisms. In contrast, pretreatment of the SW620 metastatic isolate, derived from the same patient, with IFN-gamma, CPT 11 or CDDP, but not 5-FU, enhanced ICAM-1 expression, resulting in Ag-specific CTL-mediated lysis via Fas-independent mechanisms only. Flow cytometric-based assays were then developed to measure the effects of drug treatment on caspase signaling and apoptosis incurred by tumor targets after interaction with CTL. We found that the lytic enhancement caused by drug treatment of SW480 or SW620 targets was accompanied by an increase in caspase-3-like protease activity. A peptide-based caspase inhibitor abrogated CTL-mediated apoptosis, suggesting that "chemomodulation" involved regulation of the caspase pathway. These results revealed for the first time an important role for components of the caspase pathway, such as caspase-3-like proteases, in the sensitization of human colon carcinoma cells by anti-neoplastic agents to Ag-specific CTL. Thus, certain anti neoplastic agents may display unique immunoregulatory properties that facilitate human colon carcinoma death by engaging the lytic capacity of Ag-specific CTL, which may have implications for chemoimmunotherapy strategies. PMID- 11761440 TI - Dendritic cells pulsed with tumor extract-cationic liposome complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor. AB - Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that locate in peripheral organs. It has been thought that a systemic immune response does not play a role in regression of central nervous system (CNS) tumors, because the CNS is an immunologically privileged site. However, recent advances in immunology have led to the possibility of immunotherapy using peripheral DCs against CNS tumors. Here, we investigated whether DCs pulsed with tumor extract could induce an antitumor effect against malignant glioma. Furthermore, we also investigated whether the antitumor effect become higher by pulsation with tumor extract-liposome complex, compared to pulsation with tumor extract alone. As a liposome, we used cationic small unilamellar vesicles composed of N-(alpha trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleoylphosphatidylethanolamine (DOPE) in a molar ratio of 1:2:2. After intracerebral inoculation of mouse malignant glioma GL261 cells into syngeneic C57BL/6 mice, DCs pulsed with extract from the glioma cells by sonication were administered intraperitoneally thrice weekly on days 7, 14 and 21. Tumor growth inhibition was evaluated by measuring the tumor size 1 month after the tumor inoculation. The group treated with DCs pulsed by tumor extract was inhibited in tumor progression compared with the control non pulsed DCs group, and the group treated with DCs pulsed by tumor extract and liposomes showed substantial tumor volume reductions in all the mice. Among the mice, there were several with no visible masses in their brains. Immunohistochemical study showed that the CD8-positive cytotoxic T cells (CTLs) were strongly recognized among the almost disappearing tumor cells of pulsed DCs groups. The CTLs showed a specific antitumor activity for GL261 mouse glioma cells. These findings indicated that DCs pulsed with tumor extract and liposomes might play an important role in the activation of an immune response in malignant glioma. PMID- 11761439 TI - Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity. AB - The use of fusions between dendritic cells (DCs) and tumor cells as vaccines has been proved very effective in stimulating antitumor immune responses, both in animal studies and in early human clinical trials. Because of the difficulty of purifying the hybrid cells from the fusion, fusion mixtures were used in these studies. Recently, we developed a technique using fluorescent-dye staining and fluorescence-activated cell sorting that enabled the hybrid cells to be instantly purified from the fusion mixture. In the present study, the hybrid cells were purified from a fusion between mouse DCs and B16F0 melanoma tumor cells using the new technique. The purified cells, named instant dendritomas (IDs) were then compared with fusion mixtures in stimulating antitumor immune responses. The results from cytotoxicity assays, interferon-gamma production and in vivo lung tumor metastasis demonstrated that IDs are more effective than fusion mixture in stimulating antitumor immunity. Meanwhile, there was no significant difference in the antitumor immunities activated by IDs from allogenic fusion or IDs from syngenic fusion. PMID- 11761441 TI - A TGF betaRII frameshift-mutation-derived CTL epitope recognised by HLA-A2 restricted CD8+ T cells. AB - Microsatellite instability (MSI) is recognised as genome-wide alterations in repetitive DNA sequences caused by defects in the DNA mismatch repair machinery. Such mutation patterns have been found in almost all analysed malignancies from patients with hereditary non-polyposis colorectal cancer, and in approximately 15% of sporadic colorectal cancers. In cancers with the MSI phenotype, microsatellite-like sequences in coding regions of various cancer-related genes, including transforming growth factor beta receptor type II (TGF betaRII), are targets for mutations. The TGF betaRII gene harbours a 10-bp polyadenine tract, and mutations within this region are found in 90% of colorectal cancers with MSI. The frameshift mutations result in new amino acid sequences in the C-terminal part of the proteins, prematurely terminating where a novel stop codon appears. In this study we have defined new cytotoxic T lymphocyte (CTL) epitope (RLSSCVPVA), carrying a good HLA-A*0201 binding motif, and resulting from the most common frameshift mutation in TGF betaRII. A CTL line and several CTL clones were generated from an HLA-A2+ normal donor by repeated stimulation of T cells with dendritic cells pulsed with the peptide. One of the CTL clones was able to kill an HLA-A2+ colon cancer cell line harbouring mutant TGF betaRII. This epitope may be a valuable component in cancer vaccines directed at MSI-positive carcinomas. PMID- 11761437 TI - Genesis of pituitary adenomas: state of the art. AB - In recent years, remarkable progress has been made in the understanding of the pathogenesis of pituitary tumors. Pituitary tumors originate from the uncontrolled proliferation of a single transformed cell in which an initiating event has caused a gain of proliferative function. After the initiation, promoting factors cooperate in the clonal expansion. Common oncogenes, such as ras, are only exceptionally involved. The only activating mutations identified so far are gsp mutations causing the constitutive activation of cAMP pathway. However, gsp-positive adenomas are not associated to a more aggressive tumoral phenotype. The oncogenic potential of gsp mutations is limited by a more rapid degradation of the mutant Gs(alpha) with respect to the wild-type protein, and by a faster removal of cAMP due to increased phosphodiesterase activity. Estrogen inducible gene sequences with transforming properties (pituitary tumor transforming gene (PTTG)) have been identified in human pituitary tumors. Human pituitary tumor-transforming gene (hPTTG) is involved both in early pituitary tumorigenesis, as it causes in vitro and in vivo transformation acting as a transcription activator, and in tumor progression, as it regulates the production of basic fibroblast growth factor (bFGF), a potent activator of angiogenesis and mitogenesis. Moreover, a role of cyclin D1 in pituitary tumorigenesis is emerging. The allelic loss of loci for unknown oncosuppressor genes are currently under investigation, while an exceedingly limited role for menin gene and RB1 has been demonstrated for sporadic pituitary tumors. Abnormal methylation that predisposing toward genetic instability may favor the allelic loss or the reduced expression of oncosuppressor genes, is also an emerging field of investigation. Several promoting factors, including the excessive action of physiological stimulators, the defective action of inhibitors, the susceptibility to respond to inappropriate stimuli and the locally produced growth factors, help in tumor progression. The study of homeobox genes that intervene in pituitary cell differentiation may help in expanding our knowledge in pituitary tumor cell genealogy. PMID- 11761442 TI - Biodistribution of 111indium-labeled macrophages infused intravenously in patients with renal carcinoma. AB - PURPOSE: We have previously reported a clinical trial on the intravenous injection of autologous activated macrophages (AAM) in 15 patients with renal carcinoma. The present paper concerns scintigraphic investigations performed in 11 of these patients after injection of 111indium oxinate-radiolabeled AAM. METHODS: AAM were prepared from mononuclear cells (MNC) collected by apheresis from patients treated simultaneously with granulocyte-macrophage colony stimulating factor (GM-CSF). MNC were cultured for 6 days in the presence of GM CSF and exposed for 18 h to gamma-interferon, the AAM were then separated by elutriation and injected. RESULTS: After intravenous infusion, radiolabeled AAM were transiently retained in the lungs, where they predominated in the first hour. Later on, radioactivity accumulated in liver and spleen and then decreased from the first and second day, respectively. In one patient, two foci of radioactivity were detected in the lungs 1 h after injection, and persisted thereafter. Their association with tumor lesions was uncertain. This observation possibly resulted from the presence of granulocytes in the radiolabeled AAM populations of this patient. It seems that MNC collected from GM-CSF-treated patients and cultured in the presence of GM-CSF enables the differentiation of granulocytes. CONCLUSIONS: A series of 11 investigations confirms the previously reported distribution pattern of intravenously injected AAM. It is possible that in patients treated with hematopoietic cell-mobilizing agents, granulocytes develop in cultures designed to produce monocyte-derived antigen-presenting cells. PMID- 11761443 TI - Soluble ICAM-1 in breast cancer: clinical significance and biological implications. AB - OBJECTIVES: In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule I (ICAM-1) on both tumour cells and antigen presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the effects of sICAM-1 in patients with breast cancer. PATIENTS AND METHODS: sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The effect of sICAM-1 present in the sera of patients with breast cancer upon unspecific and anti-Her-21/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51Cr-release assay and [3H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells. RESULTS: In patients with early breast cancer, serum levels of sICAM-1 were significantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a significant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No influence of sICAM-1 upon unspecific cytotoxicity, ADCC, or the ability to present antigen was observed. DISCUSSION: The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not influence unspecific cytotoxicity, ADCC, or antigen-induced T cell proliferation. PMID- 11761444 TI - Nitric oxide synthase inhibitor and IL-18 enhance the anti-tumor immune response of rats carrying an intrahepatic colon carcinoma. AB - The role of nitric oxide (NO) produced by adherent spleen cells in the systemic immunosuppression developing in tumor-bearing hosts was investigated. After therapeutic immunization of rats carrying an intrahepatic colon carcinoma, H1D2, the spleen cell antitumor immune responsiveness was analyzed. Compared to parallel immunized tumor-free rats, tumor-bearing rats (TB rats) had a greatly reduced proliferative T-cell response to wild-type tumor stimulator cells. The TB rats had a depressed proliferative response to anti-CD3 and to the superantigen SEA. TB rats with small tumors had a stronger response to IL-18-producing H1D2 stimulator cells than to wild type H1D2 cells. This was not the case with TB rats carrying larger tumors. Also the IFN-gamma production and cytotoxicity against the wild-type tumor cells and the NK sensitive YAC cells were depressed in spleen cells of TB rats after 5-day restimulation with wild-type tumor cells. A part of this immunosuppression was mediated by adherent spleen cells, mostly consisting of macrophages. An important mode of action appears to involve their production of an enhanced level of nitric oxide, since the competitive nitric oxide synthase (NOS) inhibitor L-NAME could partially counteract the suppression in vitro. We conclude that NOS inhibitors in combination with immunostimulatory cytokines, such as IL-18, could be useful tools to enhance anti-tumor immune responses in TB rats and therefore to increase the efficiency of immunotherapies. PMID- 11761445 TI - Nitric oxide in vPAG mediates the depressor response to acupuncture in stress induced hypertensive rats. AB - The hypertensive rat model was made by chronic stress of electric foot-shocks and noises. On such hypertensive rats, when anesthetized with urethane and chloralose, the electroacupuncture (EA) to bilateral "Zusanli (st.36)" acupoints for 20 min, could result in a depressor (including both systolic and diastolic pressure) and bradycardiac response as well as an attenuation in the maximum of left ventricular pressure, end diastolic pressure and +/-dp/dt. In power spectrum analysis of heart rate variability aspect, EA could increase all total variance, very low frequency component, low frequency component and the ratio of low frequency component and high frequency component. When EA with microinjection of N(omega) - Nitro- L-Arginine , a blocker of the formation of nitric oxide, into the ventral periaqueductal gray matter (vPAG), the above effects of EA were abolished or reduced significantly. The results suggest that the depressor effect of EA on stress-induced hypertensive rats might be mediated by nitric oxide in the vPAG due to activation of sympathetic inhibitory system and by attenuated cardiac activities. PMID- 11761446 TI - The effects of smiling or crying facial expressions on grip strength, measured with a hand dynamometer and the bi-digital O-ring test. AB - The effects of smiling or crying facial expressions on grip strength and the Bi Digital O-Ring Test were evaluated in this study. Ten right-handed basketball players (age group 18-28) were included in the study. Grip strength was measured with a Riester hand dynamometer and the Bi-Digital O-Ring Test successively, after the players had looked at the drawing of a "crying face" for 5 seconds from a distance of 40 cm at the eye level. Immediately afterwards they were shown the drawing of a "smiling face" and were asked to grip with the same condition. Once all 10 players carried out this experiment, the order in which the drawings were shown was reversed. We then proceeded to measure the same variables, using the Bi Digital O-Ring Test. The statistics obtained thereby were subjected to Pearsons correlation coefficient and paired t-test. Using a hand dynamometer and the Bi Digital O-Ring Test, it was found that, in both tests, the "smiling face" drawing (first crying, then smiling face: with hand dynamometer, it increased from 8.34+/ 0.97 kg to 9.18+/-0.9 kg; t=5.39,p=0.0001) increased the grip strength of the basketball players, and the "crying face" drawing (first smiling face, then crying face: with hand dynamometer it decreased from 9.35 +/- 0.90 kg to 8.51+/- 0.96 kg; t=9.81, p=0.0001) decreased the grip strength. Exposure to the smiling face drawing increased the grip strength, and exposure to the crying face decreased it, in every subject tested in this group. Similar effects were observed with the Bi-Digital O-Ring Test (first crying, then smiling: it increased from -2.80 +/- 1.13 to 2.20 +/- 1.32; t=33.54, p=0.0001; first smiling then crying: it decreased from 2.40 +/- 1.34 to -2.20 +/- 1.62; t = 15.06, p=0.0001). PMID- 11761447 TI - Auricular acupuncture increases cell proliferation in the dentate gyrus of Sprague-Dawley rats. AB - In a previous study, we have reported that acupuncture increases cell proliferation in the dentate gyrus after transient global ischemia in gerbils. In the present study, the effect of auricular acupuncture (AA) on dentate cell proliferation was examined in appropriately fed and food-deprived adult Sprague Dawley (S-D) rats. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry revealed a significant increase in cell birth in the dentate gyrus of both groups after AA treatment. In addition, the effect of AA on cell proliferation in the dentate gyrus was more profound in the food-supplied group. These findings demonstrate that AA enhances cell proliferation in the dentate gyrus of adult rats. PMID- 11761448 TI - Evaluation of acupuncture effect to chronic myofascial pain syndrome in the cervical and upper back regions by the concept of Meridians. AB - Myofascial pain syndrome (MPS) in the cervical and upper back regions is a common medical problem. The involved muscles include trapezius, multifidi, splenius cervicis, levator scapulae, supraspinatus or infraspinatus. Acupuncture is a well known method for relief of chronic pain. In this study, we evaluated the effect of acupuncture in MPS and its durability by using the concept of meridians. Twenty-nine patients with chronic MPS in the upper back and cervical regions received acupuncture 2 times per week for 3 weeks. According to the pathways of the meridians, we chose acupuncture points by the pain regions located in which parts of meridian passing (i.e. "Where the meridian passes, where to treat the disease."). We evaluated the intensity of pain by visual analog scales (VAS) and active range of motion (ROM) of neck before and after therapy. After receiving acupuncture for 3 weeks, VAS of pain fell significantly from 9.0+/-1.0 to 4.9+/ 2.5 and active ROM of neck significantly increased from 35.8+/-10.2 degrees to 61.3+/-9.4 degrees (p<0.05). The onset of symptom relief was gradual and duration of symptom relief after a course of acupuncture was average 5.3+/-1.2 days. In conclusion, acupuncture is a somewhat effective method for pain relief of patients with chronic MPS in the cervical and upper back regions. However, the effect of acupuncture with the concept of meridians on MPS is insidious and the duration of the relief is not long enough. PMID- 11761449 TI - Effect of electro-magnetic field leakage from a microwave oven on the efficacy of an antibiotic. PMID- 11761450 TI - Further characterization of the sixth transmembrane domain of Pgp1 by site directed mutagenesis. AB - PURPOSE: Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side could also affect function and to determine the extent to which altering the hydrophobic nature of residues on the hydrophobic side would impair the protein. METHODS: A full-length cDNA encoding wild-type Pgp1 from CHL cells was used as a template for site-directed mutagenesis. Eight different mutations, three on the hydrophilic side and five on the hydrophobic side, were prepared and transfected into drug-sensitive host cells. Wild-type transfectants served as controls. Drug resistance levels, RD50 values for cyclosporin A (CsA) and verapamil, iodoarylazidoprazosin (IAAP) photolabeling and verapamil-stimulated ATPase activity were evaluated. RESULTS: Substitution of any one of three amino acid residues on the hydrophilic side of TM6 disrupted function and led to alterations in drug resistance, CsA sensitivity, IAAP photoaffinity labeling, and in one case verapamil-stimulated ATPase activity. Replacement of a hydrophobic residue on the hydrophobic face of the helix with increasingly hydrophilic side-chains led to functional changes, the extent of which did not correlate with the degree of side chain hydrophilicity. Finally, while the placement of a proline residue along either face of the helix had varying effects on function, in all cases its presence interfered with verapamil-stimulated ATPase activity. CONCLUSIONS: Taken together these results indicate that both faces of TM6 mediate Pgp1 function and that the expected conformational changes resulting from proline substitutions at a variety of locations within the helix can alter the protein's enzymatic activity. PMID- 11761451 TI - Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies. AB - PURPOSE: A phase I study of the antitumor antibiotic 7-cyanoquinocarcinol, DX-52 1, was conducted in patients with refractory solid malignancies. This study sought to determine the maximum tolerated dose and principal toxicities of this agent and to characterize its pharmacokinetic behavior. METHODS: Patients were required to have adequate bone marrow, renal and hepatic function. DX-52-1 was administered by i.v. continuous infusion over a 6-h period each week for four consecutive weeks followed by a 2-week rest period, which constituted one cycle of treatment. RESULTS: Initial dose levels were 3, 6, and 10 mg/m2. An intermediate dose level of 8 mg/m2 was added after acceptable toxicity was observed at the 6 mg/m2 dose level, but dose-limiting toxicities, including life threatening ones, were seen at the 10 mg/m2 dose level in all three patients. The maximum tolerated dose (MTD) was subsequently determined to be 6 mg/m2. Because a clear pattern of toxicities was not initially evident, a larger than usual number of additional patients (16) were enrolled at the MTD to better distinguish toxicities due to the study drug from those secondary to the patients' underlying malignancies. Even at the MTD, the drug was poorly tolerated, with gastrointestinal toxicities (abdominal pain, nausea, vomiting and increased liver function tests) predominating and dose-limiting. Pharmacokinetic studies revealed that the mean maximum plasma concentration of DX-52-1 in patients evaluated at the MTD (138.8 +/- 59.3 ng/ml, n = 19) was considerably lower than the concentrations required for cytostatic or cytotoxic activity against sensitive human tumor cell lines in vitro. Further, the weekly dose intensity of the most efficacious treatment schedule identified during in vivo antitumor efficacy studies was 60 times greater than the 6 mg/m2 weekly dose tolerated by cancer patients. None of the 33 patients participating in this study, including the 22 patients evaluated at the MTD, had any response to treatment. CONCLUSION: Given the poor tolerability, the inability to achieve drug levels necessary to inhibit in vitro or in vivo tumor growth, and the lack of any responses in our study, DX 52-1, as given by this schedule, does not appear to warrant further investigation in phase II studies. PMID- 11761452 TI - Japanese experience with second-line chemotherapy with low-dose (60 mg/M2) docetaxel in patients with advanced non-small-cell lung cancer. AB - PURPOSE: To assess the efficacy and toxicity of relatively low-dose docetaxel (60 mg/m2) for previously treated advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIA-IV) NSCLC who had previously undergone at least one series of chemotherapy were enrolled. Previous paclitaxel use was allowed, but docetaxel was not. Docetaxel was administered at an initial dose of 60 mg/m2 intravenously on day 1 over 90 min every 3 weeks. RESULTS: From June 1997 to November 1999, 22 patients were entered into this study. The total number of cycles delivered to 22 patients was 53, with a median per patient of 2. Four patients achieved a partial response (PR), and the overall response rate was 18.2% (95% confidence interval 5.1-40.3%). The median time to progression was 13.7 weeks. The median survival time was 7.8 months, and the 1-year survival rate was 25%. About 73% of patients experienced grade 3 or 4 neutropenia. Neutropenic fever was observed in four patients (18%). Non-hematologic toxicities were generally mild. No treatment-related deaths occurred. CONCLUSIONS: Although the validity of the results of this study is limited due to the small and monoracial study population examined, low-dose (60 mg/m2) docetaxel for previously treated advanced NSCLC appears to yield antitumor activity and survival benefit comparable to those obtained with the conventional dose (100 mg/m2). PMID- 11761453 TI - Pharmacokinetics of MEN-10755, a novel anthracycline disaccharide analogue, in two phase I studies in adults with advanced solid tumours. AB - The doxorubicin analogue MEN-10755 has been identified as a compound with promising antitumour activity based on structure-activity studies of a new series of anthracycline disaccharides. The high antitumour activity of MEN-10755 in human tumour xenografts, including doxorubicin-resistant xenografts, and its unique pharmacological and biological properties made this novel disaccharide analogue an interesting candidate for clinical evaluation. Two pharmacokinetic phase I studies with different dosing schedules were performed in adults with solid refractory malignancies. The pharmacokinetics of MEN-10755 were studied after a 15-min i.v. infusion given once every 3 weeks or once every week for 3 weeks followed by 1 week rest. Plasma and urine levels of MEN-10755 were measured by HPLC with fluorescent detection. It was possible to combine the pharmacokinetic results of the two studies because there was no accumulation of MEN-10755 before the next infusion of MEN-10755 in the weekly study with 1 week rest. The administered dose levels on day 1 in this study were all in the lower range from the 3-weekly study. The postinfusion plasma kinetics of MEN-10755 were best described by a triexponential model. The plasma peak levels (Cmax) of MEN 10755 showed a linear relationship with the administered dose. Peak plasma MEN 10755 levels ranged between 474 and 21,587 microg/l. The mean elimination half life (T(1/2gamma)) was 20.7+/-9.0 h. The AUC(0-infinity) was proportional to the administered dose. The mean plasma clearance of MEN-10755 was 6.0+/-2.2 l/h per m2 with a mean volume of distribution (Vss) of 95.6+/-43.4 l/m2. The mean renal excretion of unchanged drug within 24 h was 4.3+/-1.8%. Compared to epirubicin and doxorubicin, the pharmacokinetics of MEN-10755 were characterized by an approximately twofold shorter terminal half-life, a much lower total plasma clearance and a much smaller volume of distribution. PMID- 11761454 TI - Comparative study between daily and 5-days-a-week administration of oral 5 fluorouracil chemotherapy in mice: determining the superior regimen. AB - BACKGROUND: Oral administration of derivatives of 5-fluorouracil (5-FU) is currently used to treat colorectal cancer in the United States. Oral chemotherapy possesses certain advantages: it is simple, easy to administer, and has few side effects. We compared conventional daily oral administration of 5-FU (daily schedule) with administration on 5 consecutive days followed by 2 drug-free days (5-days-a-week schedule) in a mouse tumor model. METHODS: The maximal tolerated dose (MTD) in the 5-days-a-week schedule and in the daily schedule were determined in 6-week-old non-tumor-bearing CDF1 male mice. In antitumor experiments, CDF1 mice were inoculated subcutaneously with Colon26 cells (1x10(6) per mouse). Antitumor efficacy was evaluated in terms of the ratio of tumor size in treated to control mice (T/C ratio). RESULTS: The MTD of 5-FU in the 5-days-a week schedule was 42 mg/kg, and in the daily schedule was 29 mg/kg. In the 5-days a-week schedule dose escalation nearly 1.4 times that in the daily schedule was possible, although the total dose over 7 days was similar between the two schedules (203 mg/kg and 210 mg/kg, respectively). When the doses of 5-FU were compared under the condition of no body weight loss, the 5-days-a-week schedule produced a comparative dose escalation of 2.1 times per day (from 20 to 42 mg/kg), and 1.5 times per total weekly amount (from 140 to 210 mg/kg) compared to the daily schedule. With regard to the antitumor effect as indicated by the T/C ratio, the 5-days-a-week schedule produced over 70% tumor suppression, whereas the daily schedule produced only 50% suppression at the MTD. Therapeutic efficacy was calculated in terms of the ratio of body weight change to antitumor effect (T/C ratio), and revealed that the MTD of 42 mg/kg 5-FU in the 5-days-a-week schedule produced a therapeutic efficacy almost three times that of the MTD of 29 mg/kg 5-FU in the daily schedule (P<0.001). CONCLUSIONS: Using oral administration of 5-FU, we confirmed that the 5-days-a-week schedule allowed dose intensity escalation and was superior to the daily schedule in both enhancement of antitumor effect and protection against adverse effects. PMID- 11761455 TI - Pharmacokinetics and tissue distribution of halofuginone (NSC 713205) in CD2F1 mice and Fischer 344 rats. AB - PURPOSE: Halofuginone (HF) inhibits synthesis of collagen type I and matrix metalloproteinase-2 and is being considered for clinical evaluation as an antineoplastic agent. Pharmacokinetic studies were performed in rodents to define the plasma pharmacokinetics, tissue distribution, and urinary excretion of HF after i.v. delivery and the bioavailability of HF after i.p. and oral delivery. MATERIALS AND METHODS: Studies were performed in CD2F1 mice and Fischer 344 rats. In preliminary toxicity studies in mice single HF i.v. bolus doses between 1.0 and 5.0 mg/kg were used. Pharmacokinetic studies were conducted in mice after administration of 1.5 mg/kg HF. In preliminary toxicity studies in male rats HF i.v. bolus doses between 0.75 and 4.5 mg/kg were used. In pharmacokinetic studies in rats an HF dose of 3.0 mg/kg was used. Compartmental and non-compartmental analyses were applied to the plasma concentration versus time data. Plasma, red blood cells, various organs, and urine were collected for analysis. RESULTS: HF doses > or = 1.5 mg/kg proved excessively toxic to mice. In mice, i.v. bolus delivery of 1.5 mg/kg HF produced "peak" plasma HF concentrations between 313 and 386 ng/ml, and an AUC of 19,874 ng/ml min, which corresponded to a total body clearance (CLtb) of 75 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. The bioavailability of HF after i.p. and oral delivery to mice was 100% and 0%, respectively. After i.v. bolus delivery to mice, HF distributed rapidly to all tissues, except brain. HF persisted in lung, liver, kidney, spleen, and skeletal muscle longer than in plasma. In the oral study, HF was undetectable in plasma and red blood cells, but was easily detectable in kidney, liver, and lung, and persisted in those tissues for 48 h. Urinary excretion of HF accounted for 7-11% of the administered dose within the first 72 h after i.v. dosing and 15-16% and 16% of the administered dose within 24 and 48 h, respectively, after oral dosing. There were no observed metabolites of HF in mouse plasma or tissues. In rats, i.v. bolus delivery of 3.0 mg/kg produced a "peak" plasma HF concentration of 348 ng/ml, and an AUC of 43,946 ng/ml min, which corresponded to a CLtb of 68 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. After i.v. bolus delivery to rats, HF distributed rapidly to all tissues, with low concentrations detectable in brain and testes. HF was detectable in some tissues for up to 48 h. HF could be detected in rat plasma after a 3 mg/kg oral dose. Peak HF concentration (34 ng/ml) occurred at 90 min, but HF concentrations were less than the lower limit of quantitation (LLQ) by 420 min. Urinary excretion of HF accounted for 8-11% of the administered dose within the first 48 h after i.v. dosing. No HF metabolites were detected in plasma, tissue, or urine. CONCLUSIONS: HF was rapidly and widely distributed to rodent tissues and was not converted to detectable metabolites. In mice, HF was 100% bioavailable when given i.p. but could not be detected in plasma after oral administration, suggesting limited oral bioavailability. However, substantial concentrations were present in liver, kidney, and lungs. HF was present in rat plasma after an oral dose, but the time course and low concentrations achieved precluded reliable estimation of bioavailability. These data may assist in designing and interpreting additional preclinical and clinical studies of HF. PMID- 11761457 TI - Enhancement of the bioavailability of oral uridine by coadministration of 5 (phenylthio)acyclouridine, a uridine phosphorylase inhibitor: implications for uridine rescue regimens in chemotherapy. AB - PURPOSE: The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in improving the oral bioavailability of uridine. PTAU is a new potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism. This compound was designed as a lipophilic inhibitor in order to facilitate its access to the liver and intestine, the main organs involved in uridine catabolism. PTAU is not toxic to mice and is fully absorbed after oral administration (100% oral bioavailability). METHODS: PTAU was administered orally to mice alone or with uridine. The plasma levels of PTAU as well as those of uridine and its catabolite uracil were measured using HPLC, and pharmacokinetic analysis was performed. RESULTS: Co-administration of PTAU with uridine elevated the concentration of plasma uridine in a dose-dependent manner over that resulting from the administration of the same dose of uridine alone, and reduced the clearance of uridine as well as the peak plasma concentration (Cmax) and area under the curve (AUC) of plasma uracil. Coadministration of PTAU at 30, 45 and 60 mg/kg improved the low oral bioavailability (7.7%) of uridine administered at 1320 mg/kg by 4.3 , 5.9- and 9.9-fold, respectively, and reduced the AUC of plasma uracil (1227.8 micromol x h/l) by 5.7-, 6.8- and 8.2-fold, respectively. Similar results were observed when PTAU was coadministered with lower doses of uridine. Oral PTAU at 30, 45 and 60 mg/kg improved the oral bioavailability of 330 mg/kg uridine by 1.8 , 2.6- and 2.8-fold, and that of 660 mg/kg uridine by 2.2-, 2.6- and 3.2-fold, respectively. CONCLUSION: The effectiveness of PTAU in improving the oral bioavailability of uridine could be useful in the rescue or protection from host toxicities of various chemotherapeutic pyrimidine analogues as well as in the management of medical disorders that are remedied by administration of uridine. PMID- 11761456 TI - Regulation of p53 target gene expression by cisplatin-induced extracellular signal-regulated kinase. AB - The extracellular signal-regulated kinase (ERK) pathway is among several signal transduction pathways that are activated in response to exposure to the DNA damage-inducing chemotherapeutic agent cisplatin. We have previously reported that inhibition of cisplatin-induced ERK activity enhances sensitivity to cisplatin. Furthermore, we have demonstrated that cisplatin-induced ERK activation is required for optimal p53 protein accumulation following cisplatin induced DNA damage. In the present study, we expanded our investigations to examine the effect of cisplatin-induced ERK activation on the expression of p53 targeted genes that have been shown to be important in the cellular response to DNA damage including Bax, Bcl-2, Bcl-x1, Cyclin G, Gadd45, p21WAF1, and Mdm2. In the ovarian carcinoma cell line A2780, cisplatin was shown to induce expression of p21WAF1, Gadd45 and Mdm2, but cisplatin had no effect on expression of Bax, Bcl-2, Bcl-x1, or Cyclin G. Inhibition of cisplatin-induced ERK activity by PD98059 resulted in decreased levels of p21WAF1, Gadd45 and Mdm2. These results provide evidence that ERK activity during the cisplatin DNA damage response, regulates in part, these cell cycle control (p21WAF1, Gadd45), DNA repair (Gadd45) and p53-regulatory (Mdm2) proteins. PMID- 11761458 TI - In vitro studies on the mechanisms of oxaliplatin resistance. AB - PURPOSE: We have previously reported that elevation of glutathione mediated by gamma-glutamyl transpeptidase is one mechanism of oxaliplatin resistance. This study explored other potential oxaliplatin resistance mechanisms with two aims: (1) to identify the differences between cisplatin and oxaliplatin in terms of drug accumulation, DNA-Pt adduct formation and repair, and (2) to determine whether defects in drug accumulation and enhanced repair of the DNA-Pt adduct contribute to oxaliplatin resistance. METHODS: The human ovarian carcinoma cell line A2780, an oxaliplatin-resistant variant A2780/C25 and a cisplatin-resistant variant A2780/CP along with an inherently cisplatin-resistant HT-29 colon carcinoma cell line were used in the study. The methods consisted of sulforhodamine-B assays, atomic absorption spectrophotometry and real-time quantitative RT-PCR. RESULTS: Significantly higher drug accumulation and DNA-Pt adduct formation were observed after exposure to cisplatin compared to after oxaliplatin in the parent A2780 cells and the oxaliplatin-resistant A2780/C25 cells. The DNA-Pt adduct formed after treatment with either drug was repaired with equal efficiency by all cell lines except A2780/CP, which repaired the DNA cisplatin adduct more efficiently than the DNA-oxaliplatin adduct. Relative to the parent line, oxaliplatin-resistant A2780/C25 cells showed reduced Pt accumulation and DNA-Pt adduct levels following exposure to oxaliplatin, but only reduced accumulation after exposure to cisplatin. The cisplatin-resistant A2780/CP cells showed reduced accumulation and DNA-Pt adduct levels after exposure to cisplatin, but only reduced DNA-Pt adduct after exposure to oxaliplatin. In comparison to A2780 cells, the inherently cisplatin-resistant HT 29 cells showed lower accumulation and DNA-Pt adduct levels after exposure to cisplatin, but displayed no difference after exposure to oxaliplatin. An enhanced repair of the DNA-cisplatin adduct was observed only in A2780/CP cells relative to A2780 cells in an 8-h period. The steady-state levels of ERCC-1 mRNA, but not of XPA, were moderately elevated in the resistant cells. Exposure to either one of the drugs resulted in an induction of XPA in all the cell lines and of ERCC-1 in cisplatin-resistant cells. There was no relationship between the level of expression of the repair genes and the DNA-Pt adduct levels or repair. CONCLUSIONS: Relative to cisplatin a lower intracellular concentration and fewer DNA-Pt adducts are sufficient for oxaliplatin to exert its cytotoxicity. Resistance to oxaliplatin is mediated by similar mechanisms of reduced drug accumulation and DNA-Pt adduct formation as resistance to cisplatin. There is no clear evidence that enhanced repair is a mechanism of oxaliplatin resistance in the cell line (A2780/C25) studied here. The findings are suggestive of yet unidentified differences between the two drugs with respect to cellular uptake and/or efflux and repair of DNA-Pt adducts. PMID- 11761459 TI - Thymidine phosphorylase as a target for imaging and therapy with thymine analogs. AB - PURPOSE: Thymidine phosphorylase (TPase; platelet-derived endothelial cell growth factor) is an attractive target for imaging and therapy because of the strong relationship between its expression in tumor biopsies and clinical outcome in many tumor types. Although the mechanism has yet to be explained, expression of TPase is highly associated with angiogenesis. METHODS: Tumor cells were phenotyped for TPase activity, and incubated with thymine or its analogs (5-X Ura). After intracellular conversion to thymidine analogs via the reverse reaction for TPase, these molecules were phosphorylated and incorporated into DNA. RESULTS: Preferential localization was found in cells with high TPase, e.g. U937. Incorporation was enhanced in cells with high TPase by coincubation with modulators such as deoxyuridine. CONCLUSIONS: 5-X-Ura molecules can be readily labeled with positron emitters, and this finding provides support for further evaluation in vivo of their potential as probes for noninvasive external imaging of TPase, both at the time of diagnosis and during maneuvers intended to manipulate TPase. If the 5-X-Ura molecules were labeled with a therapeutic isotope, e.g. 125I or 211At, selective cytotoxicity would be expected in cells with high TPase expression. However, direct evaluation of the safety in vivo of the therapeutic approach is required. The 5-X-Ura compounds constitute a novel approach to both imaging and therapy directed towards TPase. Further, there are distinct advantages to using the imaging mode to identify tumors likely to benefit from therapy with the same set of molecules. PMID- 11761460 TI - Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice. AB - PURPOSE: This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. METHODS: Athymic mice bearing subcutaneous or intracranial tumors were treated with irofulven at a 10% lethal dose with responses compared to tumor-bearing mice treated with drug vehicle. RESULTS: Irofulven was active against all tumor lines tested with growth delays ranging from 5.6 to 81.6 days (all values statistically significant, P < or = 0.001). Irofulven also produced a statistically significant (P < or = 0.001) increase in the median survival of mice bearing D-456 intracranial xenografts with a 162% increase in median survival. CONCLUSIONS: Irofulven is active in a spectrum of human glioblastoma multiforme-derived xenografts and evaluation in patients with this neoplasm is warranted. PMID- 11761461 TI - A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma. AB - PURPOSE: Preclinical and phase I clinical data suggest that 9-nitrocamptothecin (9NC) is an agent with potential anticancer activity. A phase II study was undertaken in order to evaluate the potential benefit of oral 9NC administration in patients with advanced pancreatic cancer. This was the first clinical study of 9NC in Europe. METHODS: A total of 19 consecutive patients with locally advanced or metastatic adenocarcinoma were enrolled (8 males and 11 females, aged 37-73 years). The patients were given 9NC orally five times a week, once a day. The end points of this study were toxicity, objective response rate, subjective response rate (i.e. pain control, performance status and body weight), and survival. RESULTS: An objective response was documented in 4 of the 14 evaluable patients (28.6%), while a subjective response was observed in 13 patients (92.9%). Overall median survival was 21 weeks (31 weeks in the group of 14 patients evaluable for response), and the 1-year survival was 16.7% and 23.1%, respectively. Toxicity leading to temporary discontinuation of 9NC was encountered in seven patients (36.8%), all related to a prior dose increase, while milder toxicity was observed in eight patients (42.1%). CONCLUSIONS: 9NC administered orally to patients with advanced pancreatic cancer gave promising results, while the toxicity of the therapy was mild and readily overcome. A larger scale clinical trial should be organized in order to establish the potential benefit of 9NC in patients with pancreatic adenocarcinoma. PMID- 11761462 TI - Use of PEG-asparaginase in the treatment of patients with solid tumors. PMID- 11761464 TI - Microarrays, markers of disease, and the myth of "nonhypothesis-driven" research. PMID- 11761463 TI - A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. AB - Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders. PMID- 11761465 TI - Epilepsy after head injury: the impact of impact. PMID- 11761466 TI - Imaging stroke recovery: lessons from Prozac. PMID- 11761467 TI - Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. AB - Using microarray technology, we investigated whether the gene expression profile in white blood cells could be used as a fingerprint of different disease states. Adult rats were subjected to ischemic strokes, hemorrhagic strokes, sham surgeries, kainate-induced seizures, hypoxia, or insulin-induced hypoglycemia, and compared with controls. The white blood cell RNA expression patterns were assessed 24 hours later using oligonucleotide microarrays. Results showed that many genes were upregulated or downregulated at least twofold in white blood cells after each experimental condition. Blood genomic response patterns were different for each condition. These results demonstrate the potential of blood gene expression profiling for diagnostic, mechanistic, and therapeutic assessment of a wide variety of disease states. PMID- 11761468 TI - Long-term hyperexcitability in the hippocampus after experimental head trauma. AB - Head injury is a causative factor in the development of temporal lobe epilepsy. However, whether a single episode of concussive head trauma causes a persistent increase in neuronal excitability in the limbic system has not been unequivocally determined. This study used the rodent fluid percussion injury (FPI) model, in combination with electrophysiological and histochemical techniques, to investigate the early (1 week) and long-term (1 month or longer) changes in the hippocampus after head trauma. Low-frequency, single-shock stimulation of the perforant path revealed an early granule cell hyperexcitability in head-injured animals that returned to control levels by 1 month. However, there was a persistent decrease in threshold to induction of seizure-like electrical activity in response to high-frequency tetanic stimulation in the hippocampus after head injury. Timm staining revealed both early- and long-term mossy fiber sprouting at low to moderate levels in the dentate gyrus of animals that experienced FPI. There was a long-lasting increase in the frequency of spontaneous inhibitory postsynaptic currents in dentate granule cells after FPI, and ionotropic glutamate receptor antagonists selectively decreased the spontaneous inhibitory postsynaptic current frequency in the head-injured animals. These results demonstrate that a single episode of experimental closed head trauma induces long lasting alterations in the hippocampus. These persistent structural and functional alterations in inhibitory and excitatory circuits are likely to influence the development of hyperexcitable foci in posttraumatic limbic circuits. PMID- 11761469 TI - Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. AB - In order to determine the influence of a single dose of fluoxetine on the cerebral motor activation of lacunar stroke patients in the early phase of recovery, we conducted a prospective, double-blind, crossover, placebo-controlled study on 8 patients with pure motor hemiparesia. Each patient underwent two functional magnetic resonance imaging (fMRI) examinations: one under fluoxetine and one under placebo. The first was performed 2 weeks after stroke onset and the second a week later. During the two fMRI examinations, patients performed an active controlled motor task with the affected hand and a passive one conducted by the examiner with the same hand. Motor performance was evaluated by motor tests under placebo and under fluoxetine immediately before the examinations to investigate the effect of fluoxetine on motor function. Under fluoxetine, during the active motor task, hyperactivation in the ipsilesional primary motor cortex was found. Moreover, fluoxetine significantly improved motor skills of the affected side. We found that a single dose of fluoxetine was enough to modulate cerebral sensory-motor activation in patients. This redistribution of activation toward the motor cortex output activation was associated with an enhancement of motor performance. PMID- 11761470 TI - Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord. AB - Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis. PMID- 11761471 TI - Dementia and neurodevelopmental predisposition: cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. AB - Dementia is typically thought of as a disease caused by the process of aging. Few studies have addressed the premorbid neuropsychological alterations in subjects at risk for the disease--an issue of great importance for the understanding and treatment of degenerative dementias. We used knowledge of the mutation carrier status in a family with inherited dementia to address this issue more efficiently than is possible in the general population, or in cases of inherited dementia where the mutational basis is unknown. Standard neuropsychological tests were used to detect evidence of dysfunction in frontal executive systems in 10 presymptomatic subjects with known mutation carrier status in the highly penetrant condition, frontotemporal dementia and parkinsonism linked to chromosome 17. Presymptomatic carriers demonstrated cognitive dysfunction that was not present in 6 nonmutation-carrying relatives. Strikingly, frontal executive dysfunction was apparent in some of the youngest mutation carriers many decades prior to the predicted onset of dementia. Thus, this dysfunction may reflect the native cognitive capacities of affected subjects. These results suggest a potentially important neurodevelopmental component to a dementing condition that has been predominantly considered to be a disease of aging; accordingly, this issue warrants study in other families to assess the applicability of these findings. PMID- 11761472 TI - Compensating for central nervous system dysmyelination: females with a proteolipid protein gene duplication and sustained clinical improvement. AB - A submicroscopic duplication that contains the entire proteolipid protein gene is the major cause of Pelizaeus-Merzbacher disease, an X-linked central nervous system dysmyelinating disorder. Previous studies have demonstrated that carrier females for the duplication are usually asymptomatic. We describe 2 unrelated female patients who present with mild Pelizaeus-Merzbacher disease or spastic paraplegia. In 1 patient, clinical features as well as cranial magnetic resonance imaging and brainstem auditory evoked potential results have improved dramatically over a 10-year period. The other patient, who presented with spastic diplegia and was initially diagnosed with cerebral palsy, has also shown clinical improvement. Interphase fluorescent in situ hybridization identified a proteolipid protein gene duplication in both patients. Interphase fluorescent in situ hybridization analyses of the family members indicated that the duplication in both patients occurred as de novo events. Neither skewing of X inactivation in the peripheral lymphocytes nor proteolipid protein gene coding alterations were identified in either patient. These findings indicate that, occasionally, females with a proteolipid protein gene duplication can manifest an early-onset neurological phenotype. We hypothesize that the remarkable clinical improvement is a result of myelin compensation by oligodendrocytes expressing one copy of proteolipid protein gene secondary to selection for a favorable X inactivation pattern. These findings indicate plasticity of oligodendrocytes in the formation of central nervous system myelin and suggest a potential role for stem cell transplantation therapies. PMID- 11761473 TI - McLeod neuroacanthocytosis: genotype and phenotype. AB - McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea acanthocytosis suggests that the corresponding proteins--XK, huntingtin, and chorein--might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia. PMID- 11761474 TI - Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. AB - Cerebral amyloid angiopathy is frequently found in demented and nondemented elderly persons, but its contribution to the causation of dementia is unknown. Therefore, we investigated the relation between the amount of cerebral amyloid angiopathy and the presence of dementia in 19 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. The advantage of studying hereditary cerebral hemorrhage in amyloidosis-Dutch type is that patients with this disease consistently have severe cerebral amyloid angiopathy with minimal neurofibrillary pathology. The amount of cerebral amyloid angiopathy, as quantified by computerized morphometry, was strongly associated with the presence of dementia independent of neurofibrillary pathology, plaque density, or age. The number of cortical amyloid beta-laden severely stenotic vessels, vessel-within-vessel configurations, and cerebral amyloid angiopathy-associated microvasculopathies was associated with the amount of cerebral amyloid angiopathy and dementia. A semiquantitative score, based on the number of amyloid beta-laden severely stenotic vessels, completely separated demented from nondemented patients. These results suggest that extensive (more than 15 amyloid beta-laden severely stenotic vessels in five frontal cortical sections) cerebral amyloid angiopathy alone is sufficient to cause dementia in hereditary cerebral hemorrhage with amyloidosis Dutch type. This may have implications for clinicopathological correlations in Alzheimer's disease and other dementias with cerebral amyloid angiopathy. PMID- 11761475 TI - The WldS protein protects against axonal degeneration: a model of gene therapy for peripheral neuropathy. AB - The WldS mouse is a spontaneous mutant that is characterized by the phenotype of delayed degeneration of transected nerves (slow Wallerian degeneration). Molecular genetic analysis identified a mutation in this animal that codes for a unique protein expressed in brain tissue of WldS mice. We asked whether the WldS phenotype, in addition to delaying axonal degeneration after axotomy, might provide neuroprotection against toxic neuropathy. In dorsal root ganglia (DRG) cultures, neurites from WldS transiently exposed to vincristine not only resisted axonal degeneration but resumed growth after withdrawal of the toxin. Neurites from wild type mice died rapidly and did not recover. To prove that the identified mutation and its protein product are responsible for the WldS phenotype, we used an adenoviral gene transfer system to deliver the WldS to rat DRG neurons. Rat neurons expressing the WldS protein were resistant to vincristine-induced axonal degeneration, confirming the functional significance of the identified gene mutation. These data provide evidence that the WldS protein can be neuroprotective against vincristine neuropathy, and possibly other disorders characterized by axonal degeneration. In addition, delivery of this gene to wild type cells can transfer the WldS phenotype, providing the possibility of "gene therapy" for peripheral neuropathy. PMID- 11761476 TI - Cigarette smoking and the incidence of Parkinson's disease in two prospective studies. AB - An inverse association between cigarette smoking and idiopathic Parkinson's disease has been reported in several retrospective studies, but prospective evidence is available only for men. We assessed the association between the incidence of Parkinson's disease and smoking in two large prospective cohort studies comprising men and women. New cases of Parkinson's disease were identified in the Nurses' Health Study for 1976-1996, and in the Health Professionals Follow-up Study for 1986-1996. Smoking history was assessed at baseline and updated on subsequent biennial questionnaires. In women, the age adjusted rate ratios (95% confidence intervals) for Parkinson's disease relative to never-smokers were 0.7 (0.5, 1.0) for past smokers, and 0.4 (0.2, 0.7) for current smokers. In men, the age-adjusted rate ratios for Parkinson's disease relative to never-smokers were 0.5 (0.4, 0.7) for past smokers, and 0.3 (0.1, 0.8) for current smokers. In both cohorts, the strength of the association decreased with time since quitting (among past smokers), increased with number of cigarettes per day (among current smokers), and increased with pack-years of smoking. These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women. PMID- 11761477 TI - Effect of therapeutic ionizing radiation on the human brain. AB - We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60 Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose-response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation-induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation-related changes over a broad dose range (20 to 60 Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal. PMID- 11761478 TI - Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12. AB - Spinocerebellar ataxia 12 (SCA12) is a recently identified form of autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' untranslated region of the gene PPP2R2B. We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members. The sizes of the expanded alleles ranged from 55 to 69 CAG repeats, and the sizes of the normal alleles ranged from 7 to 31 repeats. We believe our study is the first to demonstrate that SCA12 may not be as rare in some populations as previously thought. PMID- 11761479 TI - Reorganization of somatic sensory function in the human thalamus after stroke. AB - A patient with thalamic stroke underwent microelectrode-guided stereotactic thalamic exploration during surgery for control of tremor. The results of somatic sensory mapping in this patient were compared with explorations carried out during stereotactic surgery for the control of essential tremor (70 patients). There was evidence both of somatotopic reorganization and of anatomic reorganization of the representation of deep structures in the principal somatic sensory nucleus of the thalamus and the nuclei located anterior to it. This case demonstrates that thalamic reorganization can occur after a thalamic stroke and may play a role in recovery from such a stroke. PMID- 11761480 TI - Evidence for postjunctional serotonin (5-HT1) receptors in the trigeminocervical complex. AB - Units linked to stimulation of the superior sagittal sinus were identified and recorded from in the trigeminocervical complex of the anesthetized cat. Iontophoresis of glutamate NMDA receptor agonists increased the baseline-firing rate of these neurons. Coejection of sumatriptan, 4991W93, or ergometrine resulted in a significant reduction in NMDA agonist-induced increases in firing. These data establish the existence of triptan-sensitive (5-HT1) receptors on postsynaptic central trigeminal neurones. PMID- 11761481 TI - Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP. AB - To date, high human T-cell lymphotropic virus type I proviral load in patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal fluid has not been well investigated. We measured human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis patients using real-time quantitative polymerase chain reaction (TaqMan). Human T cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T-cell lymphotropic virus type I Tax-specific CD8+ T cells, as detected by peptide-loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus-specific CD8+ T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T-cell lymphotropic virus type I-infected cells and preferential expansion of human T-cell lymphotropic virus type I-specific CD8+ cells in cerebrospinal fluid may play a role in the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. PMID- 11761482 TI - Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism. AB - A genetic analysis identified 2 patients, approximately one-tenth of our patients with familial parkinsonism, who had expanded trinucleotide repeats in SCA2 genes. The reduction of 18F-dopa distribution in both the putamen and caudate nuclei confirmed that the nigrostriatal dopaminergic system was involved in parkinsonian patients with SCA2 mutation. PMID- 11761483 TI - Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis. AB - Facioscapulohumeral muscular dystrophy is caused by partial deletion of the D4Z4 repeat array on chromosome 4q35. Genetic diagnosis is based on sizing of this repeat array, which is complicated by cross-hybridization of a homologous polymorphic repeat array on chromosome 10 and by the frequent exchanges between these chromosomal regions. The restriction enzyme XapI optimizes the diagnosis of facioscapulohumeral muscular dystrophy by uniquely digesting 4-derived repeat units and leaving 10-derived repeat units undigested, thus complementing BlnI, which uniquely digests 10-derived repeat units. A triple analysis with EcoRI, EcoRI/BlnI, and XapI unequivocally allows characterization of each of the four alleles, whether homogeneous or hybrid. This is particularly useful in the case of identical sized 4-derived and 10-derived arrays, in situations of suspected facioscapulohumeral muscular dystrophy with nonstandard allele configurations, and for assignment of hybrid fragments to their original alleles. PMID- 11761484 TI - So near yet so far: neglect in far or near space depends on tool use. AB - The study of unilateral spatial neglect has shown that space can be dissociated on a peripersonal versus extrapersonal basis. We report a novel type of dissociation based on tool use in a patient suffering from left neglect. Line bisection was carried out in near and far space, using a stick and a laser pointer. A rightward bias was always found for the former, but not for the latter. Neglect thus appears to be contingent not only on distance, but also on the motor action required by the task. PMID- 11761485 TI - N-acetylaspartate--a marker of neuronal integrity. PMID- 11761487 TI - Bilateral high-frequency synchronous discharges associated with posterior fossa disorders. PMID- 11761486 TI - N-acetylaspartate: usefulness as an indicator of viable neuronal tissue. PMID- 11761488 TI - Effectiveness of intravenous immunoglobin therapy in cerebellar ataxia associated with gluten sensitivity. PMID- 11761489 TI - Cerebrospinal fluid interleukin-6 levels: a possible marker of disease activity. PMID- 11761490 TI - Delayed synaptic dysfunction of association cortices in carbon monoxide intoxication. PMID- 11761491 TI - Gone but not forgotten: declarative and nondeclarative memory processes and their contributions to resilience. AB - Cognitive psychology research challenges traditional psychoanalytic understanding of memory. The memory of facts and events is now referred to as declarative memory. Nondeclarative memory systems, in contrast, process patterns of perception, emotion, and action without representing the past in terms of any consciously accessible content. The author examines the contributions of declarative and nondeclarative memory processes to resilience. Declarative memories can promote resilience through their capacity to evoke soothing emotional responses. Nondeclarative memory processes can foster resilience through underlying the capacity to elicit and maintain supportive relationships. The concept of nondeclarative memory has potential to inform the understanding of essential psychoanalytic phenomena, including transference, countertransference, and enactment. PMID- 11761492 TI - The group-as-a-whole-object relations model of group psychotherapy. AB - The authors review the theoretical basis of group psychotherapy performed at The Menninger Clinic and demonstrate how the theory has been put into practice on two different types of inpatient units. The fundamental elements of the theory and practice used can be traced to object relations theory as originally proposed by Melanie Klein. Her work with individuals was directly applied to working with groups by Ezriel and Bion, who focused on interpreting group tension. More modern approaches have reintegrated working with individual concerns while also attending to the group-as-a-whole. Historically, these principles have been applied to long-term group treatment. The authors apply the concepts from the group-as-a-whole literature to short- and medium-length inpatient groups with open membership. They offer clinical examples of the application of these principles in short-term inpatient settings in groups with open membership. PMID- 11761493 TI - Object relations and transference in the group treatment of incest offenders. AB - After reviewing the literature on sex offenders-a literature largely devoted to behavioral, cognitive-behavioral, and relapse-prevention approaches to treatment the author proposes that an object-relational group psychotherapy treatment has a great deal to offer in the treatment of incest offenders. The author describes the parameters that distinguish group treatment of incest offenders from other object-relational group treatments. These parameters are largely related to the legally mandated nature of the treatment. The reality of enforced treatment and the very real influence treaters have on the lives of their patients supports a particular and salient transferential experience of the therapist as an authority figure who is generally also seen as harsh and arbitrary. Clinical case material clarifies how both overidentification with, and avoidance of, this authority figure role can derail treatment. The author concludes that there is potential for exploiting the reality-based treatment parameters with this population to help develop a treatment alliance that can be a powerful and effective treatment tool. PMID- 11761494 TI - Interviewing violent patients. AB - A clinical attitude to the interview of violent patients is outlined, which enables maximum safety for the clinician and usefulness of the interview findings. This approach emphasizes careful monitoring of subjective states in the patient and clinician. The author suggests an emphasis on clinical knowledge of the DSM-IV and psychodynamic diagnoses of potentially violent psychiatric patients; self-awareness of transference and countertransference; and self-care including attention to personal physical and emotional needs, de-escalation, and self-defense skills. Finally, there is need for a safe therapeutic context within which to work. PMID- 11761495 TI - A therapeutic nursery evaluation study. AB - The object of this prospective study was to evaluate the effectiveness of a therapeutic nursery program for troubled preschoolers attending the Preschool Day Treatment Center of The Menninger Clinic. Thirty-eight seriously disturbed preschoolers were assessed both at admission and at 9 months or at discharge (if before 9 months) in a pre-post design. Commonly used assessment instruments were collected by independent research clinicians. Significant gains were found in both internalizing and externalizing behaviors on the Child Behavior Checklist (CBCL). The Kohn Social Competence Scale showed significant improvement in learning, pleasurable play activities, and peer interactions. The socialization domain on the Vineland Adaptive Behavior Scale also indicated improvement beyond expectable maturation. In the Behavioral Observations test, both the capacities of the child and the qualities of the relationship were shown to be improved. As measured by the Epidemiologic Studies of Depression Scale (CES-D), mothers also became less depressed. Overall, the researchers conclude that a therapeutic nursery with a comprehensive program is an effective way to help seriously troubled preschoolers make gains in behavior, as well as in social and emotional growth. PMID- 11761496 TI - Object loss and object relations in depressive personality analogues. AB - The author investigated the extent to which self-reported early object loss and Thematic Apperception Test (TAT) measures of object relations differentiated individuals with a depressive personality from dysthymic persons and highly dependent individuals. In an undergraduate analogue sample of 54 students, those with a depressive personality reported a nonsignificantly higher proportion of object loss than did dysthymic and highly dependent participants. Those in the depressive personality and dependent groups had less complex representations of others than did those with dysthymia, and those with a depressive personalitiy and dysthymia tended to view others in a more negative, pessimistic fashion than did the highly dependent individuals. The author concludes that persons with a depressive personality can be identified, in part, by their experience of object loss and their distinctive object relations. PMID- 11761497 TI - Stamp vignette on medical science. Edward C. Kendall-Nobel laureate. PMID- 11761498 TI - Religion, spirituality, and medicine: how are they related and what does it mean? PMID- 11761499 TI - Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial. AB - OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit. PMID- 11761500 TI - Decline in bilateral orchiectomy for prostate cancer in Olmsted county, Minnesota, 1956-2000. AB - OBJECTIVE: To assess long-term secular trends in the utilization of bilateral compared with unilateral orchiectomy in the community. PATIENTS AND METHODS: This population-based descriptive study reviewed medical records of all Olmsted County, Minnesota, men undergoing orchiectomy between 1956 and 2000. RESULTS: Over the 45-year study period, 381 Olmsted County men had a first unilateral orchiectomy, while 431 underwent bilateral orchiectomy (including 8 with a second unilateral orchiectomy). There was no change over time in the age-adjusted utilization of unilateral orchiectomy, which was performed for a wide range of indications, mostly cryptorchidism and testicular malignancy. Most bilateral procedures, on the other hand, were in elderly men for castration, and trends over time generally paralleled those reported for prostate cancer in this community. CONCLUSION: The declining incidence of prostate cancer in recent years, combined with a shift to earlier stages and younger ages at diagnosis, and the development of pharmacological approaches to hormonal manipulation have led to a dramatic decline in the utilization of bilateral orchiectomy, while unilateral orchiectomy rates have remained unchanged. PMID- 11761501 TI - Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985 2000. AB - OBJECTIVE: To describe the causes, complications, and histological appearance of nonbacterial thrombotic endocarditis (NBTE) in a surgical population compared with those in previously reported autopsy series. PATIENTS AND METHODS: Cases were identified by reviewing the surgical pathology reports for all cardiac valvular specimens removed at Mayo Clinic, Rochester, Minn., between 1985 and 2000. Archived microscopic slides and medical records were reviewed for each study patient. RESULTS: The study group consisted of 30 patients (20 female and 10 male), with a mean age of 49 years (range, 15-89 years). Of these 30 patients, 28 had single valve involvement (19 mitral, 8 aortic, and 1 tricuspid), and 2 had involvement of both their mitral and aortic valves. An underlying immune-mediated disorder was identified in 18 patients (60%), including primary antiphospholipid syndrome (in 8), rheumatic heart disease (in 6), systemic lupus erythematosus (in 2), and rheumatoid arthritis (in 2), 15 (83%) of whom were women. Of the remaining 12 patients with no autoimmune disease, only 5 (42%) were women. No patient had metastatic malignant disease or disseminated intravascular coagulopathy. Systemic embolization was documented in 10 patients (33%), 8 of whom had cerebral involvement. Valvular vegetations were visualized by echocardiography before surgery in 8 patients and were suspected but not confirmed preoperatively in 1 patient. All vegetations consisted primarily of platelets and fibrin. The site and appearance of vegetations did not vary with the underlying disease state. CONCLUSIONS: In contrast to previously reported autopsy series, NBTE in a surgical population was more commonly associated with autoimmune disorders than malignancy or disseminated intravascular coagulopathy. Women were affected twice as often as men. Systemic embolization, particularly to the brain, was prominent in both surgical and autopsy series. Vegetations had a similar appearance regardless of the specific underlying disease. An antemortem diagnosis of NBTE in a patient with no known risk factors should prompt a search not only for occult malignancy, as suggested by autopsy studies, but also for autoimmune or rheumatic diseases, particularly the antiphospholipid syndrome. PMID- 11761502 TI - Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AB - OBJECTIVE: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack. PATIENTS AND METHODS: We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test. RESULTS: CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs. 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs. 24.0 micromol/ L; P = .02). CONCLUSION: Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL. PMID- 11761503 TI - Ciliary dyskinesia associated with hydrocephalus and mental retardation in a Jordanian family. AB - OBJECTIVE: To describe the presentation and genetic transmission of ciliary dyskinesia syndrome associated with hydrocephalus and mental retardation in 3 generations of a family. PATIENTS AND METHODS: A large Jordanian family included 9 individuals in 3 generations with recurrent pulmonary infections; 4 male siblings have been diagnosed as having mental retardation, and a maternal uncle was believed to have been similarly affected. Chromosome analysis of the family showed a normal karyotype. RESULTS: Electron microscopy of the nasal cilia from 3 affected siblings showed features of primary ciliary dyskinesia. Computed tomographic scans of the brains of all 4 affected siblings showed hydrocephalus. CONCLUSIONS: The recurrent pulmonary infections and hydrocephalus in this large Jordanian family are likely related to ciliary dyskinesia, which appears to follow an autosomal recessive mode of inheritance. The unusual presentation of ciliary dyskinesia, hydrocephalus, and mental retardation may be due to a new genetic mutation. PMID- 11761504 TI - Religious involvement, spirituality, and medicine: implications for clinical practice. AB - Surveys suggest that most patients have a spiritual life and regard their spiritual health and physical health as equally important. Furthermore, people may have greater spiritual needs during illness. We reviewed published studies, meta-analyses, systematic reviews, and subject reviews that examined the association between religious involvement and spirituality and physical health, mental health, health-related quality of life, and other health outcomes. We also reviewed articles that provided suggestions on how clinicians might assess and support the spiritual needs of patients. Most studies have shown that religious involvement and spirituality are associated with better health outcomes, including greater longevity, coping skills, and health-related quality of life (even during terminal illness) and less anxiety, depression, and suicide. Several studies have shown that addressing the spiritual needs of the patient may enhance recovery from illness. Discerning, acknowledging, and supporting the spiritual needs of patients can be done in a straightforward and noncontroversial manner. Furthermore, many sources of spiritual care (e.g., chaplains) are available to clinicians to address the spiritual needs of patients. PMID- 11761506 TI - The management of melanoma and nonmelanoma skin cancer: a review for the primary care physician. AB - In the United States, the incidence of skin cancer is greater than that of all other cancers combined, and early diagnosis can be lifesaving. A substantial public health concern, skin cancer is increasingly being diagnosed and managed by primary care physicians. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (known collectively as nonmelanoma skin cancer) and malignant melanoma are the most common cutaneous malignancies. Shave biopsy is usually performed if BCC is suspected; punch biopsy is preferred if SCC is thought to be present. The choice of biopsy techniques depends on the presumed depth of the lesion. Treatment has 3 goals: complete eradication of the cancer and preservation or restoration of normal function and cosmesis. Risk of recurrence or metastasis determines whether the tumor is high risk or low risk. Based on the level of risk, treatment options are considered, including whether the patient can be treated by a primary care physician or should be referred to a dermatologist. Choice of treatment approach depends on the tumor's location, size, borders, and growth rate. The standard treatment approaches are superficial ablative techniques (electro-desiccation and curettage and cryotherapy) used primarily for low-risk tumors and full-thickness techniques (Mohs micrographic surgery, excisional surgery, and radiotherapy) used to treat high-risk tumors. Removal of the entire tumor is essential to limit and prevent tumor recurrence. PMID- 11761505 TI - Current concepts in the diagnosis, pathogenesis, and treatment of autoimmune hepatitis. AB - Autoimmune hepatitis has a global distribution and affects all ages. Genetic factors strongly influence susceptibility, clinical expression, and treatment response. The diagnosis of autoimmune hepatitis has been codified by an international panel. An acute or fulminant presentation is recognized but not a cholestatic form. Subclassifications by predominant autoantibody profile have been proposed, but they lack etiologic and prognostic differences. Autoantibodies continue to be characterized to improve diagnostic specificity, predict outcome, and identify pertinent antigenic targets. Cytosolic enzymes are prime candidates as autoantigens. DRB1*0301 and DRB1*0401 are the susceptibility alleles in Caucasoid Northern Europeans and North Americans, and they also affect clinical expression and treatment outcome. Other autoimmune promoters affecting cytokine production and immunocyte activation may act in synergy with the susceptibility alleles to affect disease behavior. Cell-mediated and antibody-dependent forms of cytotoxicity are probably interactive pathogenic mechanisms, and novel site specific therapies are feasible because these mechanisms are defined. Potent new immunosuppressive agents are emerging from the transplantation arena, but prednisone alone or in combination with azathioprine remains the mainstay of treatment. Corticosteroid therapy is effective but not ideal. PMID- 11761507 TI - Step care therapy for hypertension in diabetic patients. AB - For diabetic patients, a goal blood pressure lower than 130/80-85 mm Hg is strongly supported by clinical trial results. We review the agents, sequence, and dosing used in clinical trials and propose a treatment algorithm. Multiagent antihypertensive therapy is required to attain goal blood pressure in most patients. Step sequences to obtain this goal are suggested. In general, we favor initial therapy with an angiotensin-converting enzyme inhibitor, followed by the addition of a diuretic. The presence of comorbid conditions may dictate variation from this scheme. The effect of antihypertensive agents on established cardiovascular diseases, proteinuria, renal function, and metabolic factors is discussed. Tailored recommendations for specific clinical scenarios are described. PMID- 11761508 TI - Caudate hemorrhage as a possible complication of midodrine-induced supine hypertension. PMID- 11761509 TI - Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients. PMID- 11761510 TI - Photodynamic therapy for the palliation of esophageal cancer: expensive endoscopic technique or inexpensive cancer treatment? PMID- 11761512 TI - Medical advice for international travelers. PMID- 11761511 TI - Medical advice for international travelers. PMID- 11761513 TI - Diet and activity to the rescue again. PMID- 11761514 TI - Gel may end hair loss in cancer patients undergoing chemotherapy. PMID- 11761515 TI - Rosacea is more than red face. PMID- 11761516 TI - Doppler radar keeps patients' blood flowing at its best during surgery. PMID- 11761517 TI - AMA urges HCFA to mandate physician collaboration. PMID- 11761518 TI - Medicare compliance programs. PMID- 11761519 TI - Herbs and the common cold. PMID- 11761520 TI - Make them laugh. Therapeutic humor for patients with grief-related stress or anxiety. PMID- 11761521 TI - Clinical management of type 2 diabetes. An overview for nurse practitioners. PMID- 11761522 TI - Insulin resistance syndrome. Unraveling the mystery. PMID- 11761523 TI - Syndrome X: a case study. PMID- 11761524 TI - Herbal approaches to diabetes care. Uses demand more scientific study. PMID- 11761525 TI - Transdermal estrogen replacement therapy. An overview of today's issues. PMID- 11761526 TI - Caring for sunburn. PMID- 11761527 TI - Get in the game. Principles of the preparticipation physical. PMID- 11761528 TI - Chronic and acute renal failure. Primary care issues. PMID- 11761529 TI - Update on contraception. PMID- 11761534 TI - 'Mixed' billing raises questions. PMID- 11761535 TI - Irritable bowel syndrome: an update on treatment options. PMID- 11761536 TI - Leukotriene modifiers. Expanded role may be on horizon. PMID- 11761537 TI - Inhaled corticosteroids. In the treatment of asthma. PMID- 11761538 TI - Increasing compliance with asthma treatments. PMID- 11761539 TI - Obstructive sleep apnea in children. Reversing the trend of underdiagnosis. PMID- 11761540 TI - Quieting the '100-day cough'. A primer on pertussis. PMID- 11761541 TI - Caregivers who hurt. The tragedy of elder abuse. PMID- 11761542 TI - It takes a village. NP-owned nonprofit clinic captivates a community. Interview by Jolynn Tumolo. PMID- 11761543 TI - Screen all patients for alcoholism. PMID- 11761544 TI - Standard for stroke is emergency care. PMID- 11761545 TI - Gainsharing arrangements. PMID- 11761546 TI - Telling a teen she's HIV-positive. PMID- 11761547 TI - Heart murmurs in children. A systematic approach to cardiac evaluation. PMID- 11761548 TI - Allergies and asthma. Don't overlook the missing link. PMID- 11761550 TI - Chlamydia: the silent STD. PMID- 11761551 TI - Sweet 16 and infected. Sexually transmitted diseases in adolescents. PMID- 11761549 TI - Hide and seek. Make sure HPV infection doesn't escape diagnosis. PMID- 11761552 TI - Get moving! A mantra for perimenopausal women. PMID- 11761553 TI - Ties that bind. Understanding meralgia paresthetica. PMID- 11761554 TI - Soft tissue injuries. Management of common presentations. PMID- 11761555 TI - The new AIDS paradigm: living with metabolic complications. PMID- 11761556 TI - Sudden development of bilateral cataract in a child with Dubowitz syndrome: a case report. AB - The Dubowitz syndrome is a rare, autosomal recessive disorder including intrauterine growth retardation, craniofacial abnormalities, mental retardation and eczematous skin eruption. Ocular problems occur in about 20%: strabismus, blefarophimosis, ptosis, telecanthus and epicanthal folds being the most frequent ones. We present a three years old girl, diagnosed with Dubowitz syndrome, with sudden visual loss due to bilateral cataract. PMID- 11761557 TI - Diplopia from skew deviation in Ramsey-Hunt syndrome. A case report. AB - OBJECT: Presentation of a 34-year-old pregnant woman with skew deviation due to peripheral vestibular dysfunction caused by herpes zoster oticus. METHODS: A multidisciplinary approach (neuroophthalmology, otorhinolaryngology, neuroradiology) revealed the diagnosis of Ramsey-Hunt syndrome. CASE REPORT: The patient presented with painful herpes zoster vesicles of the left ear, associated with a rotatory vertigo and hearing loss. Otorhinolaryngological examination showed a unilateral peripheral vestibular loss, a nystagmus towards the unaffected right side, no facial nerve dysfunction and a left perception hearing loss, mainly in the frequencies between 2-6 KHz. The patient was treated with Zovirax IV. Neuroradiological examination (MRI without contrast) revealed no abnormalities. Vertical diplopia from skew deviation was noted +/- 10 days after onset of herpes zoster oticus. Neuroophthalmological and orthoptic examination showed a comitant right hypertropia of 6 diopters and a spontaneous nystagmus to the right. CONCLUSION: Skew deviation can be caused by a sudden unilateral cochleo-vestibular loss as described by A.B. Safran. (4,6,7,8). PMID- 11761558 TI - Incidence of nd:Yag capsulotomy after lens implantation of an Acrylic IOL in one eye and a Silicone IOL in the other eye of the same patient: a preliminary study. AB - We retrospectively reviewed the charts of 40 patients who underwent an uneventful phacoemulsification in both eyes and had an Acrylic IOL (AcrySof) implanted in one eye and a Silicone IOL (SI 30/S 140) in the other. A subset of 18 patients had a mean follow up of 1 1/2 year. In the Acrylic group 1 patient (5.5%) underwent a posterior Yag-capsulotomy. In the Silicone group 6 patients (30%) underwent a Yag-capsulotomy. (2 anterior--4 posterior) (p = 0.04) Acrylic IOL's were associated with a significantly reduced incidence rate of Yag-capsulotomy compared with silicone IOL's after 1 1/2 years. PMID- 11761559 TI - Delayed diagnosis of retinoblastoma. AB - The aim of our study was to evaluate the age of the patient and the stage of retinoblastoma at diagnosis and to determine the time delay between the first symptoms noticed by proxy and the diagnosis of retinoblastoma. Therefore, thirty three children between the age of zero and seven with the diagnosis of uni- or bilateral retinoblastoma were studied retrospectively. Thirty-one patients were diagnosed with advanced disease; two patients had small tumors. The mean time delay between the first clinical symptoms and the diagnosis of retinoblastoma was 3.2 months (range 2 months to 1 year). In our study most children with retinoblastoma were diagnosed with advanced disease. In some patients there was a significant time delay between the first symptoms and the final diagnosis of retinoblastoma. Better parental and environmental information regarding symptoms of retinoblastoma could help to assure earlier detection of tumors. PMID- 11761560 TI - Invasive squamous cell carcinoma of the conjunctiva. AB - A 75-year-old man, known with Morbus Kahler, was referred with a history of uveitis and hypopyon at the left eye. The uveitis did not respond to any steroid treatment. It was complicated with high intraocular pressure. Anterior chamber punction showed atypical cells of epithelial origin. Several weeks prior to this presentation an atypical pterygium of the same eye was biopsied. Histopathologic examination at that time showed mild atypical actinic changes. The biopsy specimen was reviewed in our laboratory and revealed an invasive squamous cell carcinoma originating from the bulbar conjunctiva. The eye was eventually enucleated. Histologic examination of the enucleated eye showed invasion of the cornea, sclera, trabeculum, anterior chamber angle and choroid by a muco epidermoid squamous cell carcinoma. PMID- 11761561 TI - Clinicopathologic correlation of surgically removed submacular tissue. AB - The histologic appearance of a consecutive series of 200 neovascular membranes was analyzed. Specific angiographic manifestations of exudative age-related macular degeneration such as classic or occult choroidal neovascularization, vascularized pigment epithelial detachment, tear of the retinal pigment epithelium, polypoidal choroidal vasculopathy and deep retinal vascular anomalous complex correspond with specific histoarchitectural patterns. PMID- 11761562 TI - Cadherin expression in the eye. AB - E(pithelial)-cadherin and N(eural)-cadherin are transmembrane cell-cell adhesion molecules, belonging to the subfamily of classical cadherins. The expression of E and N-cadherin is spatiotemporally regulated and associated with a variety of normal morphogenetic events. The expression of E- and N- cadherin is also involved in carcinogenesis. E-cadherin functions as a tumor-suppressor. N cadherin, however, is associated with cancer progression. The study of the expression pattern of E- and N-cadherin in the normal and tumorous eye is the aim of our research. PMID- 11761563 TI - Cell biological mechanisms underlying posterior capsule opacification: search for a therapy. AB - The present paper overviews our recent studies for PCO prevention using an in vitro human capsular bag model and application of hyperthermia and photodynamic therapy with Bacteriochlorin A as the sensitizer as described in previous papers. These studies clearly showed that both treatments are successful in vitro and almost completely reduce the proliferation of lens epithelial cells on the posterior capsule and thus are potential candidates to eliminate the occurrence of PCO in vivo. Hyperthermia has a threshold temperature between 55 degrees C and 60 degrees C which makes this approach not very useful for in vivo application. Threshold conditions for PDT/BCA are much more moderate. Recent preliminary in vivo studies in the rabbit showed that using the in vitro threshold conditions, the formation of a ring of Soemmering and outgrowth of lens epithelial cells on the posterior capsule is significantly reduced. However, these conditions have an adverse affect on the corneal stroma and endothelium. Studies of PDT conditions which further reduce LEC outgrowth without affecting the corneal integrity are in progress. PMID- 11761564 TI - Preliminary results of the FRO project: chromosomal abnormalities in primary uveal melanoma. AB - Uveal melanoma is the most common primary intraocular tumor in adults in the western world. Recent studies indicate that the presence of cytogenetic abnormalities in tumor cells is strongly linked with prognosis. The purpose of this project is the detection of chromosomal abnormalities in a series of frozen tumors (retrospective study) and of fresh tumor tissues (prospective study) and to correlate these results with other prognostic factors and survival. PMID- 11761565 TI - ADCON-L hydrogel as a vitreous substitute: preliminary results. AB - The ideal vitreous substitute has still to be found. This report concerns the preliminary results of a translucent hydrogel, ADCON-L, used successfully in neurosurgery. We have used this hydrogel as a vitreous substitute in the right eye of New-Zealand albino rabbits following vitrectomy. The follow-up period was four weeks and the evaluation was followed by biomicroscopy, indirect ophthalmoscopy, and electroretinography. The results obtained suggest a potential retinotoxicity of this hydrogel as shown by the statistically significant reduction of the mean B-wave amplitude at day 14 (p < 0.05) and day 28 (p < 0.005), as well as an important postoperative inflammatory reaction. Another transparent formulation of the same molecule is currently under investigation. PMID- 11761566 TI - [Make difference between pain and pain! A basis for correct choice of treatment is differentiation of pain-generating mechanisms]. PMID- 11761567 TI - [Health effects of exposure to magnetic fields? Epidemiology, unknown mechanisms]. PMID- 11761568 TI - [Treatment guidelines for refractory angina pectoris now available. Therapeutic methods varying between behavior therapy and heart transplantation]. AB - Refractory angina pectoris is defined as severe angina despite optimal medical and surgical/invasive treatment (CABG, PTCA). The epidemiology of this condition is unknown. The estimated yearly incidence is 2,000 patients in Sweden and 30,000 50,000 patients in Europe. The patient group is growing as a result of improved therapy. A number of additional treatment modalities have been developed during the last decades. The article summarises the scientifically and clinical basis of these treatments and gives recommendations concerning their use. PMID- 11761569 TI - [Acupuncture therapy today. Background, clinical use, mechanisms]. AB - Acupuncture, an over 2000 years old therapeutic method stemming from traditional Chinese medicine (TCM), is nowadays used mainly as a sensory stimulation method, the main indication being long-term nociceptive pain. Symptoms of nausea, mouth dryness, climacteric flushes, vascular disturbances and bladder dysfunction may also be relieved by acupuncture. In addition, the method is used in alcohol and drug detoxification programs. Analgesia by acupuncture seems to work through stress induced analgesia (strong, painful) while therapeutic acupuncture (gentle, painless) probably works through a local tissue healing effect and central anti stress mechanisms. PMID- 11761570 TI - [International consensus on low-frequency electromagnetic fields: "possibly carcinogenic"]. PMID- 11761571 TI - [Guidelines and general advice on male circumcision]. PMID- 11761572 TI - [Cell transplantation in Parkinson disease]. PMID- 11761574 TI - [Increasing number of patients consider alternative and complementary medicine--a challenge for future health care]. PMID- 11761575 TI - [CAM--complementary or alternative medicine--in Lakartidningen!?]. PMID- 11761573 TI - [Complementary and alternative medicine--some ethical reflections]. AB - CAM, Complementary and Alternative Medicine, exposes the clinician to a number of ethical challenges. While sound scientific evidence supporting clinical procedures is always recommendable, it is nevertheless acceptable to use CAM procedures if they can reasonably be judged as harmless, and if conventional therapy offers little or no help. This is in line with the last revision of the Helsinki declaration. The physician must establish a close and trustful relationship with her patient and be open to the potential residing in CAM for a more profound understanding of clinical practice. PMID- 11761576 TI - [Natural preparations--drugs produced from the vegetable kingdom]. PMID- 11761577 TI - [Water as elixir of life and cure]. PMID- 11761578 TI - [Physicians without borders: "Food bombs" in Afghanistan discredit humanitarian help]. PMID- 11761579 TI - [Value and limits of alternative medicine]. PMID- 11761580 TI - [Psychological tests in forensic psychiatry on solid ground]. PMID- 11761581 TI - [Future physicians or ancient physicians?]. PMID- 11761582 TI - [Underreporting according to the Lex Maria]. PMID- 11761583 TI - [Yes, what are we supposed to do with our life?]. PMID- 11761584 TI - [Guidelines followed criticism concerning truth disclosure when it comes to cancer via telephone]. PMID- 11761585 TI - CMA balks as Calif. eyes Mexico to recruit docs to serve Latinos. PMID- 11761587 TI - Frustrated with managed care 'lite,' radicals see virtue of competition. PMID- 11761586 TI - Health care talk unseemly when United States is at war. PMID- 11761588 TI - Compensation monitor. Hospitals scramble for cutting-edge personnel. PMID- 11761589 TI - The uninsured: how health plans can do well by doing good. PMID- 11761590 TI - Attacks prompt examination of mental health care funding. PMID- 11761591 TI - Overlooked in Cipro hype: other anti-anthrax meds. PMID- 11761592 TI - Healing power of color as cheap as coat of paint. PMID- 11761593 TI - Telemedicine: cost-effective management of high-risk pregnancy. AB - PURPOSE: To evaluate the cost-effectiveness of telemedicine services in patients diagnosed with preterm labor (PTL). DESIGN: Women hospitalized with a diagnosis of PTL during a 3-year study period were identified within a health maintenance organization. INCLUSION CRITERIA: singleton gestation, stabilized after tocolysis and discharged from the hospital, and participation in the HMO's preterm-birth prevention program. After a PTL diagnosis, telemedicine services (home uterine activity monitoring with daily telephonic nursing contact) were authorized by the payer. The decision to prescribe telemedicine services was made by each patient's individual physician. Two groups of patients were identified: those who received telemedicine services (telemedicine group), and those who received standard care without the adjunctive outpatient service (control group). METHODS: Descriptive and statistical methods were used to compare maternal demographics, pregnancy outcome, antepartum hospitalization, delivery, nursery, and outpatient services. PRINCIPAL FINDINGS: One hundred women were identified: 60 in the telemedicine group and 40 in the control group. Gestational age at diagnosis of PTL was similar at 29.4 +/- 3.8 weeks, telemedicine group vs. 28.0 +/- 7.4 weeks, control group (P = 0.252). The telemedicine group had a significantly later mean gestational age at delivery (38.2 +/- 1.4 vs. 35.3 +/- 3.8), higher mean birth weight (3224 +/- 588 vs. 2554 +/- 911), fewer mean total nursery days (2.4 +/- 1.8 vs. 14.9 +/- 26.4), and less frequent admission to the neonatal intensive care unit (6.7 percent vs. 40 percent) than the control group (all P < 0.005). The total mean cost per pregnancy was $7,225 for the telemedicine group and $21,684 for the control group. This represented average savings of $14,459 per pregnancy using telemedicine services. CONCLUSION: Following an episode of PTL, use of telemedicine services can be a cost-effective tool to improve pregnancy outcome. PMID- 11761594 TI - Determining who is covered by HIPAA privacy regulation. PMID- 11761595 TI - Managed care outlook. Government still bullish on Medicare+Choice growth. PMID- 11761596 TI - Why do women suffer from sick building syndrome more often than men?--subjective higher sensitivity versus objective causes. AB - Office workers often report so-called sick building syndrome (SBS) symptoms affecting the skin, mucous membranes and nervous system. The recurring higher prevalence of SBS in women was investigated using questionnaire and ergonomic data from the German ProKlimA-Project. The hypothesis that working conditions and job characteristics for women are inferior to those of men was tested for groups of risk factors. Finally, gender-specific multiple logistic regression models were compared. It was found that 44.3% of women (n = 888) and 26.2% of men (n = 576) suffer SBS with significant differences between men and women for many variables. Considering sub-groups--supposing the same circumstances in psycho social and work-related conditions--gender-specific SBS prevalence rates differ as for the whole sample, e.g. 35.9% of women with the most favourable job characteristic suffer SBS (men: 19.4%), 53.0% of women with the most unfavourable job characteristic suffer SBS (men: 33.3%). These results show that women suffer more SBS than men independent of personal, most work-related and building factors. Multiple logistic models define self-reported acute illness, job satisfaction, software quality and job characteristics as significant gender independent risk factors. Number of persons/room, self-reported allergy and smoking are characteristic female risk factors. Age is a significant risk factor only in men. PMID- 11761597 TI - Sign of eye irritation in female hospital workers and the indoor environment. AB - The relationships between indoor environment factors and signs of eye irritation were studied in a sample of female personnel with (n = 112) and without (n = 64) mucous membrane symptoms working in 36 nursing departments at geriatric hospitals in the municipality of Trondheim, Norway. The indoor climate was characterised by high room temperature (interquartile range 23.0-23.7 degrees C), low relative air humidity (interquartile range 17-26%) and high outdoor airflow rate, as indicated by low indoor levels of carbon dioxide (interquartile range 490-650 ppm). An altered microbial flora was observed in nine of the departments, and Aspergillus fumigatus was found in three of these. Five of the hospitals were situated in urban parts of the municipality near roads with heavy traffic. In the initial analyses decreased tear-film stability (BUT) was observed in subjects working in departments with increased dust settlement rate (P = 0.03), in hospitals situated in urban areas with heavy traffic (P < 0.001), and in subjects working in departments with presence of A. fumigatus (P = 0.04). Increased conjunctival staining (CS) was related to alteration of the microbial flora. In the final multivariate analyses statistically significant relationships were observed between BUT and dust settlement rate and urban vicinity of workplace and between CS and alteration of the microbial flora. PMID- 11761598 TI - The distribution of soiling by coarse particulate matter in the museum environment. AB - Soiling measurements are needed to address strategies to control dust and determine its sources. There is no widely recognized method for dust monitoring in museums, but we used sticky samplers to collect deposited coarse particulate matter, and both manual microscopic observations and image analysis for determining soiling potential in the museum environment. We adopt fractional area covered by deposited particles as a surrogate for soiling and the covering rate (unit: s-1) as a measure of the rate of soiling. It was clear that visitor flow was a major contributor to soiling, such that soiling mechanisms in different museums could be compared after measurements were normalised on a per capita basis. The proximity of visitors to objects was another important factor with the soiling declining with distance from visitor pathways (a half-distance of about 0.5 m), which suggests soiling of objects on open display could be reduced by increasing the distance from visitors. PMID- 11761599 TI - Airborne birch and grass pollen allergens in street-level shops. AB - Polluted urban outdoor air may be enriched with large amounts of submicronic respirable pollen allergen particles that penetrate into street-level shops. The objectives of the study were to map concentrations of birch and grass pollen allergens in indoor air of street-level shops and to explore the effect of electrostatic air cleaning under authentic working conditions, indoor air samples were collected in May and July 1999 in two shops. Allergens were quantified by a direct on sampling filter in solution (DOSIS) luminescence immunoassay. The average concentration of airborne indoor birch pollen allergen in the shop with air cleaning was estimated to be 20 +/- 9 SQ/m3 (mean +/- SD) compared to 31 +/- 17 SQ/m3 (mean +/- SD) of that without. The air cleaner reduced the indoor air birch pollen allergen concentration by on average 26 to 48% (P < 0.05). Corresponding figures for airborne indoor grass pollen allergen concentrations were 14 +/- 7 SQ/m3 and 17 +/- 8 SQ/m3, indicating a statistically non significant (t-test) average 18% reduction of allergen by air cleaning. Excluding two observations with poor fit to the statistical model a significant (P < 0.05) average 27% reduction was obtained. Substantial amounts of airborne birch and grass pollen allergens may occur in street-level shops during flowering seasons. PMID- 11761600 TI - Sorptive interactions between VOCs and indoor materials. AB - This study was carried out using various materials (carpet, gypsum board, upholstery, vinyl and wood flooring, acoustic tiles, and fruit) that were exposed to eight gaseous volatile organic compounds (VOCs) (isopropanol, MTBE, cyclohexane, toluene, ethylbenzene, tetrachloroethene, 1,2-dichlorobenzene, and 1,2,4-trichlorobenzene) in electro-polished stainless-steel chambers. Dynamic responses in VOC concentrations were used to determine linear adsorption and desorption rate coefficients and equilibrium partition coefficients. A linear adsorption/desorption model was used to effectively describe the interactions between VOCs and indoor surface materials for short-term source events (10 h). Relationships between sorption parameters and chemical vapor pressure and the octanol-air partition coefficient were observed. Carpet was identified as the most significant sorptive sink for non-polar VOCs. Virgin gypsum board was observed to be a significant sink for highly polar VOCs. Sorptive interactions between non-polar VOCs and indoor materials were not affected by variations in relative humidity. However, increases in relative humidity were observed to increase the degree of sorption of isopropanol to carpet. PMID- 11761601 TI - A coupled airflow and source/sink model for simulating indoor VOC exposures. AB - In this paper, a numerical model is presented to study the indoor air quality (IAQ) in a room with different emission sources, sinks, and ventilation methods. A computer program, ACCESS-IAQ, is developed to simulate the airflow pattern, the time history of the contaminant concentrations in the occupied zone, and the inhalation exposures. The program developed may be useful for IAQ professional to design healthy and comfortable indoor environments. A numerical study has been carried out to predict the effectiveness of a displacement ventilation and a mixing ventilation on volatile organic compound (VOC) removal in a model office. Results from the numerical predictions show that when a "wet" emission source (a freshly painted wood stain) is distributed uniformly across the floor area with sinks (gypsum board) from the four vertical walls, displacement ventilation has consistently lower exposure at the breathing level of the occupant in the room. Such an effect is mainly due to the higher ventilation efficiency of displacement ventilation compared to the mixing ventilation. The simulation results also show that the walls adsorb significant amounts of VOCs during the first hour and act as secondary sources thereafter. PMID- 11761602 TI - Effects of environmental and test conditions on VOC emissions from "wet" coating materials. AB - In this paper, numerical simulations have been conducted to study the effects of key environmental and test conditions (air velocity, temperature, film thickness, and sample application time) on volatile organic compound (VOC) emissions from a "wet" coating material (wood stain). Simulation results indicate that air velocity and sample application time only significantly affect the emission profiles in the early stage. Film thickness, on the other hand, affects long-term emissions. Temperature can affect both the short-term and long-term emissions. PMID- 11761603 TI - Gambling, delinquency, and drug use during adolescence: mutual influences and common risk factors. AB - The purpose of this study was threefold: (1) to assess the possible mutual influence between gambling, substance use, and delinquency over a two-year period during mid adolescence, (2) to test whether variables that are usually predictive of delinquency and substance use also predict gambling, and (3) to test whether the links between the three problem behaviors could be, at least partially, accounted for by common antecedent factors (impulsivity, parental supervision, and deviant friends) assessed during early adolescence. Seven hundred and seventeen boys participated in the study. Impulsivity, parental supervision, and friends' deviancy were collected when participants were 13 and 14 years of age. Gambling, substance use, and delinquency were collected through self-reports at ages 16 and 17 years. Results showed no influence or modest influence of problem behaviors on each other from age 16 to age 17 years, once current links and auto correlations were accounted for. Conversely, the cross-sectional links between the three problem behaviors at each age were moderately high. Impulsivity, low parental supervision, and deviant friends were predictively related to each problem. Finally, a significant, although modest, portion of the covariance between the three problem behaviors was accounted for by these three predictors. The present findings contradict previous findings about the influence of gambling on other problem behaviors and support the notion of a "general problem behavior syndrome" fed by generic risk factors. PMID- 11761604 TI - Social influences involved in children's gambling behavior. AB - Children (N = 130) in grades 4 and 6 from various schools in the Greater Montreal Region completed a questionnaire concerning their gambling behavior and played a computer-simulated roulette game individually (baseline trial & post-test trial) and in groups (same and mixed gender dyads or triads: group trial). The purpose of this design was to measure children's betting behavior (via average wagers) and to determine if any changes in betting occur as a result of playing in groups of two, three, same and/or different gender peers. Results of repeated measures analyses reveal that during individual and group play, males consistently exhibit higher average wagers than females. Average wagers of females and mixed gender groupings appear to be most affected by the group condition. Females were found to increase their average wagers when playing with females and males. Female dyads' wagers increase significantly during group play, indicating they are dramatically affected by the group game. Most changes resulting from group play were generally maintained over a relatively short period of time in the post-test condition. Results are interpreted with respect to the importance of the influence of the peer group on children's gambling behavior. Future directions for research are suggested. PMID- 11761605 TI - Outcome of Minnesota's gambling treatment programs. AB - This study measured the outcome of four state-supported outpatient gambling treatment programs in Minnesota. The programs were developed specifically for the treatment of pathological gamblers and offered multiple modalities of treatment including individual, group, education, twelve-step work, family groups, and financial counseling. The therapeutic orientation was eclectic with an emphasis on the twelve steps of Gamblers Anonymous (GA) and a treatment goal of abstinence. The sample included 348 men and 220 women treated between January 1992 and January 1995. A pretest-posttest design was utilized with multidimensional assessments obtained at intake, discharge, six-months, and twelve-months post-discharge. Variables assessed included a range of clinical and outcome variables. At six month follow-up, 28% reported that they had abstained from gambling during the six months following discharge and an additional 20% had gambled less than once per month. Almost half of the sample (48%) showed clinically significant improvement in gambling frequency at six month follow-up. Outcome variables of gambling frequency, SOGS scores, amount of money gambled, number of friends who gamble, psychosocial problems, and number of financial problems, all showed statistically significant improvements from pretreatment to follow-up. The treatment programs yielded outcome results similar to those reported for alcohol and drug abuse treatment programs. PMID- 11761606 TI - "If you do not gamble, check this box": perceptions of gambling behaviors. AB - Most adults in the U.S. have participated in one or more gambling activities. However, many people engage in gambling activities without considering themselves as gamblers. Four hundred and forty-nine university students returned surveys about their participation in gambling activities. After completing a questionnaire recording the style and frequency of gambling participated in, respondents were asked to indicate whether or not they gambled. Results indicated that gamblers participated in twice as many forms of gambling activities as those who classified themselves as non-gamblers. Scratch tickets and lottery tickets were not generally considered gambling unless purchased frequently. Casino visits, bingo, dog races, football pools, golf matches, local poker games, and other card games were more likely to be viewed as gambling, especially when engaged in frequently. Subjects who had gambled on at least one occasion with bookies, dice games, video poker in a bar, dog or cock fights, or off track betting almost always identified themselves as gamblers. It is recommended that further research be conducted to clarify the gambling activities, and frequency of those activities, that influence a person's perceptions of gambling. PMID- 11761607 TI - [Genetic control of sex differentiation in humans]. AB - The current literature results on genetic control of sex differentiation and morphogenesis of the human reproductive system are reviewed. Several examples of the nosologic forms caused by mutations in the genes analyzed are considered. PMID- 11761608 TI - [Suppression of alpha-fetoprotein gene expression in somatic hybrids of AFP positive and AFP-negative clones of rat hepatoma]. AB - The presented study is devoted to investigation of molecular mechanisms regulating alpha-fetoprotein (AFP) gene expression at transcriptional level. The study was carried out on AFP-positive and AFP-negative clones of rat hepatoma McA RH 7777 that also differ in hepatocyte nuclear factors (HNF) 1 and 4 transcription levels. To examine a hypothesis of existence in AFP-non-producing clones a transcriptional factor that downregulates this gene expression, we have obtained somatic hybrids of AFP-positive and AFP-negative clones. In the obtained hybrids AFP gene expression is decreased while expression of HNF1, one of the main AFP promoter activators, is maintained. These data indicate an existence of a repressor in AFP-negative clones that determines AFP gene downregulation regardless of the HNF1 expression level. PMID- 11761609 TI - [Interspecies conjugation of Escherichia coli-Streptomyces globisporus 1912 using integrative plasmid pSET152 and its derivatives]. AB - Streptomyces globisporus 1912 produces a novel angucycline antitumor antibiotic landomycin E (LE). To study the LE biosynthetic gene cluster in detail, a system for the conjugal transfer of the integrative plasmid pSET152 from Escherichia coli into S. globisporus 1912 has been developed. It was shown that this plasmid integrates into two sites of the S. globisporus chromosome and is stably inherited under nonselective conditions. pSET152+ exconjugants of the strain 1912 are characterized by a significant decrease in LE synthesis (by 50-90%). A negative effect of pSET152 integration on antibiotic production was observed even upon the use of the recipient strain with increased LE synthesis, although in this case, the level of LE production in ex-conjugants was 120-150% of that in the original strain 1912. Based on pSET152, a vector system for gene knockouts in S. globisporus was developed. The effectivity of this system was shown in the example of disruption of the lndA gene encoding the key enzyme of LE synthesis (beta-ketoacylsynthase). Inactivation of this gene was shown to lead to the cessation of LE biosynthesis. PMID- 11761610 TI - [Individual polymorphism by RAPD markers in spring generation of the Colorado beetle Leptinotarsa decemlineata (Say)]. AB - Genetic diversity of Colorado potato beetle in a natural population from Fastovskii rayon, Kiev oblast was estimated using RAPD. The level of polymorphism for RAPD markers was far higher in the spring generation than in the sample obtained from the same locality in summer of the preceding year. The frequency of individual RAPD markers was found to differ in males and females of potato beetle. PMID- 11761611 TI - [Modeling the periodically-changing predictable response to mutagen exposure in CBA/LacY mice in a successive inbred generations]. AB - A hypothesis on the genetic determination of periodic fluctuations of the sensitivity to the mutagen thioTEPA in successive inbred generations of mice has been earlier put forward. This study was the initial stage of testing this hypothesis. The mouse strain CBA/LacY was divided into two substrains, which differed in the rate of generation change. As a result, two colonies of isogenic mice differing by 10-12 generations with respect to the inbred age were obtained. Both the rate and range of variations in the mutagen sensitivity (four generations per period of the cycle and 20-40% of cells with chromosome aberrations after the standard dose of 2.5 mg/kg of thioTEPA, respectively) in 19 generations of the "fast" substrain agreed with earlier data. The response of the "slow" substrain corresponded to the expected response of the "fast" substrain after the given number of generations. In the mice of generations F142 and F146 that lived simultaneously and differed in thioTEPA sensitivity, the effects of the carcinogen benzo[a]pyrene (BaP) were significantly different. The levels of these effects corresponded to the levels of the responses to thioTEPA. The data obtained agree with the hypothesis tested. PMID- 11761612 TI - [Transforming growth factor alpha (TGFalpha) modulates the effect of genomic imprinting and prolongs the development of parthenogenetic murine embryos]. AB - The effect of transforming growth factor alpha (TGF alpha) on the development of diploid parthenogenetic mouse embryos (CBA x C57BL/6)F1 was studied. The embryos were in vitro treated with the TGF alpha at the stage of morula. Upon reaching the blastocyst stage, each embryo was implanted into uterus of a pseudopregnant female. At a dose of 5 ng/ml, the TGF alpha was found to improve development of parthenogenetic embryos before implantation, increase significantly the number of developing blastocysts, and promote embryo implantation into uterus. After treatment with TGF alpha at a dose of 10 ng/ml, 4% of parthenogenetic embryos reached the stage of 30-45 somites and had forelimb and hindlimb buds; the embryo size from vertex to sacrum was 2.0 to 3.8 mm. A well-developed placenta was observed in 6% of TGF alpha-treated parthenogenetic embryos that reached the somite stages. In the parthenogenetic embryos with the most prominent development (42-45 somites) treated with 10 ng/ml of TGF alpha, the placental diameter was 4.0 to 4.2 mm on day 12 of gestation, which is close to the placental size of the normal (fertilized) 11-day-old mouse embryos. Our results suggest that endogenous TGF alpha can modulate the effects of genomic imprinting significantly improving formation of trophoblast derivatives and promoting longer postimplantation development of parthenogenetic embryos. PMID- 11761613 TI - [Inheritance of a sign of a weekly expressed greenbug resistance in sorghum]. AB - Combined inheritance of oligogenes (Sgr1, Sgr4, Sgr5, and Sgr6) and a weakly expressed resistance to infestation with virulent greenbug clones was studied in sorghum. Under these conditions, the resistance was shown to depend on the interaction between minor resistance genes of the host plant and the virulence genes of the pest rather than on the "residual effect" of oligogenes. The minor genes can be independent of or weakly linked to the major resistance gene. They differentially interact with phytophage genotypes and, contrary to Van der Plank's postulates, are not responsible for the long-term (horizontal) resistance. The possibility of rapidly overcoming the effect of minor genes was confirmed by observation of seasonal dynamics of a natural aphid population on a resistant variety. PMID- 11761614 TI - [Polymorphism of hordeins in Ethiopian barley]. AB - Using starch gel electrophoresis, polymorphism of hordein-encoding loci Hrd A, Hrd B, and Hrd F was studied in 147 accessions of local Ethiopian barley varieties. Loci Hrd A, Hrd B, and Hrd F were shown to have 26, 36, and 4 alleles, respectively. The allele frequencies in the collection examined varied from 0.17 to 45.72%. For loci Hrd A and Hrd B, families of blocks of hordein components were found. Based on the allele frequencies and their combinations at loci Hrd A and Hrd B as well as the numbers of families of component blocks in hordeins A and B, we identified genotypes that could be considered as the most ancient in Ethiopia. A catalog of hordein variant encoded by these loci was created. The list of hordein genetic formulas for the studied accessions is presented. PMID- 11761615 TI - [Analysis of the genetic structure of the breeding nucleus of the Russian population of purebred Thoroughbred horses at the Extension locus using molecular DNA typing]. AB - Results of the first in Russia survey of the gene pool of the breeding nucleus of the Russian population of thoroughbred horses by means of PCR analysis of the E (Extension) locus MC1R gene mutations are presented. The data on the structure of breeding populations from the leading stud farms Voskhod and Oros with regard to color phenotypes as well as genotype and allele frequencies are presented. The population structure parameters are discussed with respect to possible specific features of microevolution processes. PMID- 11761616 TI - [Allelotyping the Hras1 minisatellite: formation of carcinogenic risk groups and predicting the course of non-small cell lung cancer]. AB - PCR-based typing of Hras1 minisatellite alleles was carried out in 226 non-small cell lung cancer (NSCLC) patients and 207 unaffected controls. Application of this method permitted detection of four common (a1 to a4) and 25 other alleles, differing from any common allele by one or more repeat units. Depending on their frequency in control group, these alleles were defined as intermediate or rare (the frequency over 0.5% or less than 0.5%, respectively). It was established that the frequency of rare alleles in the group of NSCLC patients (7.1%) was statistically significantly higher than in healthy individuals (2.2%, p = 0.002), while the difference in the distribution of common and intermediate alleles between the compared groups was not statistically significant. In addition, rare Hras1 alleles were more frequent (p = 0.02) among nonsmoking patients compared to the patients subjected to of tobacco carcinogens. The presence of "heavy" (a3-a4) alleles was associated with an increased risk of low-differentiated and/or actively metastasizing tumors and also with the risk of lung cancer in the patients under 50 years of age (p < 0.05). These data indicate that an approach including application of modern highly sensitive techniques of Hras1 allele typing in combination with preliminary examination of healthy control population can be employed for identifying carcinogenic risk groups as well as for prognosis of the NSCLC clinical course. PMID- 11761617 TI - [Analysis of polymorphic variants of renin-angiotensin system genes in polymetabolic syndrome and non-insulin-dependent diabetes]. AB - Polymorphisms of the genes for angiotensin-converting enzyme (ACE) and angiotensinogen, the proteins of the renin-angiotensin system (RAS), were tested for association with the polymetabolic syndrome (PMS) and non-insulin-dependent diabetes mellitus (NIDDM) in the Moscow population. The insertional (I) allele and genotype II of the ACE gene proved to be associated with PMS. A significant difference in allele and genotype frequency distributions of the (CA)n microsatellite of the 3'-untranslated exon of the angiotensinogen gene was revealed between randomly sampled individuals and patients with PMS and IDDM from the Moscow population. PMID- 11761618 TI - [Structure of the gene pool of ethnic groups from the Altai-Sayan region from data on mitochondrial polymorphism]. AB - Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the four Turkic-speaking ethnic groups of Altai-Sayan highlands, Southern Altaians (Altai-Kizhi), Khakassians, Shorians, and Sojots, were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E, G, A, B, and F) and Caucasoid (H, U, T, J, and K) mtDNA lineages. All the populations studied had a strongly pronounced Mongoloid component, the frequency of which was 88.2% in Sojots, 75.9% in Khakassians, 67.4% in Altaians, and 64.3% in Shorians. Maximum frequency of the Caucasoid component (35.7%) was observed in Shorians. Phylogenetic and statistical analyses of the mtDNA group frequency distribution patterns in the gene pools of the ethnic populations of Altai-Sayan highlands and the adjacent territories showed that the populations of the region fell into three groups. The first group included Khakassians, Tuvinians and Altaians, the second group consisted of Sojots, Buryats, and Mongols, while the third group was composed of Uigurs, Kazakhs, and Kyrgyzes. The isolated position of Shorians among the populations examined can be explained by their different anthropological composition and their presumptive relatedness to Finno-Ugric populations of Siberia. PMID- 11761619 TI - [Variability in mitochondrial DNA in Russian inhabitants from Krasnodar Krai, Belgorod and the lower Novgorod region]. AB - Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations from the European part of Russia (Krasnodar Krai, Belgorod, and Nizhnii Novgorod oblast). This analysis revealed that mitochondrial gene pool of Russians was represented by the mtDNA types belonging to groups H, V, pre-V, HV*, J, T, U, K, I, W, and X. The major groups (average frequency over 5%) were H, V, J, T, and U. Mongoloid admixture in Russians, constituting only 1%, was revealed in the form of mtDNA types of groups C and D. Analysis of the frequency distribution of the mtDNA type groups indicated the absence of genetic differences between the Russian populations studied. PMID- 11761620 TI - [Computer modeling of joint selection response of MGE patterns and a polygenic system]. AB - Using computer simulation, selection response of three genome patterns- polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)--were studied. In each generation of selection, variability of each pattern type was described by on UPGMA tree. Stringent positive truncation selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95-96% and 70-80% of respectively enforced and non-enforced active polygenic alleles were fixed (2-3% and 16-17% lost). In all generations, Hkn < or = Dkn of the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85-88% (lost for 11-12%); marker MGEs, for 60-70 (lost for 21-25%); and independent copies, for 30-40 (lost for 50-60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16:3 for modifier MGEs, 15:6 for marker MGEs, and 25:28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random. PMID- 11761621 TI - [Trans-effect of modifiers on position-effect variegation in a set of euchromatin heterochromatin rearrangements in Drosophila melanogaster]. AB - The effects of suppressors of position-effect variegation were studied in a set of euchromatin-heterochromatin rearrangements of the X chromosome accompanied by inactivation of the gene wapl. The rearrangements differed from one another in the size of the heterochromatic block adjacent to euchromatin, with the euchromatin-heterochromatin border remaining unchanged. In one rearrangement (r20), the position effect caused by a small block of adjacent heterochromatin may be determined by its interaction with the neighboring main heterochromatic region of the X chromosome. Chromosome 3 (the RT chromosome) was found to have a strong suppressing effect on all rearrangements, irrespective of the amount of heterochromatin adjacent to euchromatin. Su-var(3)9, a known suppressor of the position-effect variegation, had a considerably weaker suppressing effect. The RT chromosome had the strongest suppressing effect on the rearrangement r20. PMID- 11761622 TI - [Use of artificial neuronal nets in automation of analysis and genetic identification of electrophoretic spectra of gliadin from durum wheat]. AB - Each wheat cultivar has a characteristic spectrum of gliadins. This makes it possible to use blocks of the components of reserve proteins as genetic markers when estimating seed quality. However, identification of the blocks that constitute the electrophoretic spectrum is a complicated task. For this purpose artificial neural network (ANN) technology is proposed. Based on experimental data, a teaching database and testing databases have been created. ANN was shown to be highly efficient (efficiency up to 100%) expert system for deciphering the electrophoretic spectra of gliadins of durum wheat cultivars. PMID- 11761623 TI - [Genetics of color of the ornamental carp: inheritance of underlying dark coloration]. AB - In ornamental carps from the collection of the Experimental Station, All-Russia Research Institute of Fresh-Water Fisheries, fish with a dirty dark tint of body color among orange and white fish were found. This coloration was shown to be due to the presence of black pigment cells in the lower skin layer. In the outer skin layers these cells were almost entirely absent. This color type was found to be determined by the presence of at least one of alleles B1' or B2' of digenic system B1, B2, which is responsible for the development of melanophores in fish skin. Each of the genes of this digenic system is represented by three alleles with the following order of dominance: B > B' > b. PMID- 11761624 TI - Successful management of lipid-lowering programs. AB - Health improvement programs must today face the hurdle of demonstrating their value to the business professionals in managed care organizations. These individuals have vast fiscal responsibilities but often lack a medical background. It is imperative that program advocates not only identify these key decision makers, but present an argument for program adoption by using data these decision-makers are most familiar with: grounded, quantitative results. This tactic can enhance the likelihood of a program being implemented. To validate the proposed program to the MCO business sector, it must address a disease or condition that is characterized by wide variation in physician practice, high cost, high volume, and an evidence base that supports the proposed intervention. PMID- 11761625 TI - An employer coalition to reduce costs and improve adherence. AB - A coalition of employers based in Ohio is addressing statin utilization on multiple fronts. By working through a new pharmacy benefits manager, it reduced its costs for statins by 9 percent over the course of one year, chiefly by replacing a relatively high-cost statin with a lower-cost statin believed to be of similar efficacy. The coalition also has worked on an individual basis with high prescribers of a high-cost statin, requesting them to consider a lower-cost statin. That effort also has met with success. Meanwhile, the coalition has launched a mail-based program intended to improve adherence among patients taking statins. PMID- 11761626 TI - The economics of lipid management. PMID- 11761628 TI - Clinical aspects of dyslipidemia. PMID- 11761629 TI - Adolescents with psychiatric disorders: when to treat? And with what? PMID- 11761630 TI - Anxiety disorders in children and adolescents with bipolar disorder: a neglected comorbidity. AB - OBJECTIVE: We describe a consecutive clinical sample of children and adolescents with bipolar disorder to define the pattern of comorbid anxiety and externalizing disorders (attention-deficit hyperactivity disorder [ADHD] and conduct disorder [CD]) and to explore the possible influence of such a comorbidity on their cross sectional and longitudinal clinical characteristics. METHODS: The sample comprised 43 outpatients, 26 boys and 17 girls, (mean age 14.9 years, SD 3.1; range 7 to 18), with bipolar disorder type I or II, according to DSM-IV diagnostic criteria. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). To shed light on the possible influence of age at onset, we compared clinical features of subjects whose bipolar onset was prepubertal or in childhood (< 12 years) with those having adolescent onset. We also compared different subgroups with and without comorbid externalizing and anxiety disorders. RESULTS: Bipolar disorder type I was slightly more represented than type II (55.8% vs 44.2%). Only 11.6% of patients did not have any other psychiatric disorder; importantly, 10 subjects (23.5%) did not show any comorbid anxiety disorder. Comorbid externalizing disorders were present in 12 (27.9%) patients; such comorbidity was related to the childhood onset of bipolar disorder type II. Compared with other subjects, patients with comorbid anxiety disorders more often reported pharmacologic (hypo)mania. PMID- 11761631 TI - The pharmacologic treatment of the early phase of first-episode psychosis in youths. AB - OBJECTIVES: To summarize available knowledge about pharmacologic treatments that are used for first-onset (or early) psychosis in youths, with particular consideration of the prodromal stage and the effectiveness and safety of novel antipsychotic drugs and mood stabilizers. METHOD: A computerized search of medical databases (for example, Medline and Embase), a manual searching of articles and textbooks, and the use of vignettes to highlight treatment issues. RESULTS: There are limited data about the effectiveness and safety of psychotropic agents for youths with psychosis and scarce information about the drug treatment of the prodromal stage of early psychosis in all age groups. The available data are encouraging, although the newer agents are not without safety concerns. CONCLUSIONS: Despite the paucity of studies, there is a range of psychotropics that may be used in the early stages of psychotic illness in youths. Drug choice is influenced by several factors, including the clinical picture, side effect profile, and patient preference. In certain situations, the decision may be not to use medication. PMID- 11761632 TI - Developmental neurobiology: implications for pediatric psychopharmacology. AB - Pediatric psychopharmacology can only be properly understood within the context of developmental neurobiology. Normal maturation of the brain is characterized by the complex anatomic, molecular, and organizational changes required for optimal adaptive functioning. In many areas of the developing nervous system, neurons, cell processes, neurotransmitters, and trophic nerve growth factors are produced in far greater numbers and in different areas than in the mature brain. Psychopathology and stressful environments can lead to enduring changes in brain structure and functioning. A few select psychopharmacological treatments are reviewed to assess their potential impact on CNS development. More clinical and basic science studies are needed to determine whether current treatments have neurotoxic or neuroprotective effects when administered over extended critical early periods of the lifespan. PMID- 11761633 TI - Psychosocial risk factors in poststroke depression: a systematic review. AB - OBJECTIVE: To review systematically the psychosocial risk factors for poststroke depression. METHODS: Medline was searched using the key words "poststroke depression" (PSD) for the period January 1, 1966, to June 30, 2000; using the key words "cerebrovascular disease" and "depression" it was searched from June 1, 1996, to June 30, 2000. Corollary articles were obtained from the bibliographies. Inclusion criteria were as follows: original research in French or English; prospective, case-control or cross-sectional study design; assessment of PSD in the first 6 months following the stroke; an acceptable definition of depression; an acceptable definition of stroke; and at least one psychosocial risk factor. Interrater reliability was tested for the selection and quality of the articles. A qualitative risk factor analysis was conducted. RESULTS: The risk factors most consistently associated with PSD are a past history of depression, past personal psychiatric history, dysphasia, functional impairments, living alone, and poststroke social isolation. Risk factors not associated with PSD are dementia and cognitive impairment. Controversial risk factors are age, socioeconomic status (SES), prior social distress, dependency in regard to activities of daily living (ADL), and sex. CONCLUSIONS: Over approximately 30 years, some 25 qualitative studies have addressed psychosocial risk factors for PSD. Further studies should aim for quantitative analysis. The results suggest that identifying psychiatric history and preventing social deterioration and impairment should be part of multidisciplinary efforts to care for poststroke patients. PMID- 11761634 TI - Antipsychotic drugs and obesity: is prolactin involved? AB - OBJECTIVES: To correlate the anthropometric indexes (Body Mass Index [BMI] and Waist-Hip ratio [WHR]) with the serum prolactin levels in a heterogeneous population of patients treated with typical antipsychotic (AP) drugs. METHODS: We evaluated BMI, WHR, and fasting serum prolactin of inpatients (n = 105) and outpatients (n = 122) treated with APs, in outpatients receiving other psychotropic drugs (OPDs) (n = 77), and in drug-free subjects (n = 33). Outpatients had free access to food, whereas the inpatient sample comprised people with a monotonous diet of approximately 2000 Kcal daily. RESULTS: Prolactin correlated positively with the BMI in the whole group of AP-treated outpatient men (P = 0.03) and with the WHR in AP-treated inpatient men (P = 0.053). Regarding treatment duration, prolactin and BMI correlated positively in men consecutively treated for more than 1 year (P = 0.023). By contrast, a trend toward a negative correlation between prolactin and BMI was observed in AP treated outpatient women (P = 0.08). No significant correlation, or even a trend, was observed in the other groups. CONCLUSIONS: Prolactin may be involved in AP induced weight gain, particularly in men. Future studies should characterize the period of maximal prolactin impact on body weight during AP treatment. Specific populations particularly sensitive to hyperprolactinemia might be identified as well. The negative correlation between prolactin and BMI detected in AP-treated women resembles the dampened prolactin response observed in severe primary obesity. PMID- 11761635 TI - Predictors of success and satisfaction in the practice of psychiatry: a preliminary follow-up study. AB - BACKGROUND: Few studies have examined the predictors of psychiatrists' perceived success and personal satisfaction with their careers. The present study examines self-reported success and personal satisfaction with their careers in a cohort of psychiatrists followed for more than 20 years. METHODS: A total of 29 psychiatrists, all of whom had participated in a study during their residency 21 to 24 years earlier, completed a self-report questionnaire. The first set of questions addressed the type and characteristics of their professional practice; the second set assessed aspects of their nonprofessional practice; and the third set assessed aspects of their nonprofessional, personal lifestyles. The personality traits of neuroticism and extraversion were assessed during the residency years and were used as predictors. Composite measures of self-perceived external success and personal satisfaction were computed. Regression models were constructed to determine the best predictors of these composite measures. RESULTS: Neuroticism proved to be a significant predictor of external success but not of personal satisfaction, with higher scores predicting a lower rating of perceived external success. There were 2 practice characteristics--involvement with research and practising from an orientation other than psychoanalytic--that predicted perception of success. One personal lifestyle characteristic--the perception that one's nonprofessional life sustained professional life--also predicted perception of success. The best predictor of personal satisfaction was overall satisfaction with nonprofessional aspects of life. CONCLUSIONS: Personality, nonprofessional social support, and engaging in research are associated with greater perceived success and personal satisfaction with a career in psychiatry. PMID- 11761636 TI - [Validation of the French version of the Health of the Nation Outcome Scales (HoNOS-F)]. AB - OBJECTIVE: This study reports the validation of the French version of the Health of the Nation Outcome Scales (HoNOS-F), a questionnaire developed to measure health and social functioning of people with mental illness. METHOD: Once each statement was tested for readability, the scale was administered to 3 samples of people suffering from severe mental disorders to estimate its reliability and validity. More specifically, tests were run to establish the internal consistency, the stability, and the interrater reliability of the HoNOS-F. Confirmative factor analyses and mean differences according to age, sex, and diagnosis were also conducted to evaluate respectively construct- and criterion related validity. RESULTS: Coefficients obtained from the various tests show that the scale is reliable only when the total score is used. The confirmatory factor analyses indicate that the observed data do not fit the 2 proposed models, a unidimensional model and a 4-dimension model. However, the scale did show criterion-related validity. CONCLUSIONS: Results of the present study converge with those obtained on the original widely used English version. Therefore, we suggest that clinicians use the questionnaire by referring to each item separately and by considering such patient characteristics as age, sex, and diagnosis. We also suggest that researchers wishing to evaluate health and social functioning of persons with serious mental disorders use the total score. Caution is, however, warranted when interpreting the total score for a French-speaking population, because the factorial solution 1-dimension model did not prove to be satisfactory. PMID- 11761637 TI - Frequency of borderline personality disorder in a sample of French high school students. AB - OBJECTIVE: To estimate the frequency of borderline personality disorder (BPD) in French high school students. METHOD: A random sample of high school students (n = 1363) ranging in age from 13 to 20 years agreed to complete a questionnaire, the Screening Test for Comorbid Personality Disorders (STCPD); 107 of them volunteered to be interviewed. We assessed this group using the Revised Diagnostic Interview for Borderlines (DIB-R). We conducted a regression analysis to determine a cut-off for BPD diagnosis with the STCPD. RESULTS: We estimated the overall frequency of BPD to be 10% for boys and 18% for girls. After a peak of frequency at age 14 years for both sexes, the frequency increased significantly again in late adolescence. CONCLUSION: This study found a high frequency of BPD in French adolescents, which adds to questions regarding the validity of diagnosing this disorder in adolescents. PMID- 11761638 TI - Factorial structure of the Sensation-Seeking Scale-Form V: confirmatory factorial analyses in nonclinical and clinical samples. AB - OBJECTIVE: The factor structure of the Sensation-Seeking Scale (SSS)-Form V was studied in 2 large French samples, using confirmatory factorial analyses (CFA) to test the 4-dimensional model of sensation seeking postulated by Zuckerman. METHOD: The study included 769 healthy subjects and 659 patients who met the DSM IV criteria for substance use disorders or eating disorders and completed the SSS. The correlation matrices for each of the samples were analyzed using CFA. RESULTS: In each sample, we found the 4-factor model to be replicable. CONCLUSION: The multidimensionality of sensation seeking is supported by the results, and the 4-dimensional model of sensation seeking identified by Zuckerman can be explored in French-speaking people. PMID- 11761639 TI - Suicide in adolescents in Italy (1969-1994). PMID- 11761640 TI - Does risperidone reduce concomitant substance abuse in cases of schizophrenia? PMID- 11761641 TI - Re: Developmental disability training in Canadian psychiatry residency programs. PMID- 11761642 TI - The phenomenology of perfectionism: "yumpity". PMID- 11761644 TI - Atypical antipsychotics and neuroleptic malignant syndrome. PMID- 11761643 TI - Evaluation of droperidol in the acutely agitated child or adolescent. PMID- 11761645 TI - Treatment of mixed mania with risperidone and mood stabilizers. PMID- 11761646 TI - Special session on medical liability. PMID- 11761647 TI - An open letter from a concerned medical student. PMID- 11761648 TI - Study indicates influenza vaccine beneficial for college athletes. PMID- 11761649 TI - Improvements achieved in medical care to Medicare beneficiaries. PMID- 11761650 TI - Endovascular repair of abdominal aortic aneurysms: our early experience. AB - Endovascular repair of abdominal aortic aneurysms (AAA) seems to hold the potential for decreased perioperative mortality and morbidity associated with the standard open repair by eliminating major surgical exposure of the aorta and prolonged aortic cross-clamping. After several years of FDA-approved clinical trials of multiple aortic-stented grafts, the FDA, in September 1999, approved two devices (the ANCURE and the AneuRx) for commercial use in the United States. We implanted the first device in the Tri-State area at the Charleston Area Medical Center (CAMC) on Feb. 6, 2000, and this study reviews our early experiences with 15 patients utilizing these two devices at CAMC. PMID- 11761651 TI - Developmental outcomes in very low birth weight infants: a six-year study. AB - Advances in neonatal care have led to survival of more Very Low Birth Weight (VLBW) infants weighing < 1,500 grams with growing concerns about neuro developmental outcomes. To identify relationships between outcomes and birth weight, we evaluated 213 VLBW infants over a six-year period using a standardized test to identify relationships between outcomes and birth weight, and participation in early intervention programs at a one-year follow-up. Average Mental Development Indices were obtained for the majority of infants across all birth weight categories with the smallest group (500-750 grams) scoring significantly lower than infants in all other categories. Infants who did not participate in early intervention scored better which suggests this group was healthier and less likely to need intervention services. Further clarification of the salient components of early intervention is recommended in future studies. PMID- 11761652 TI - Tetanus: a case report, epidemiology review and recommendations for immunization compliance. AB - Tetanus is a forgotten disease in the United States since many practicing primary care physicians have not seen a case of the disease in their career. A 73-year old woman presented with dysphagia two weeks after she obtained a superficial laceration while gardening. Within days, the jaw spasms and subsequent respiratory compromise that necessitated five weeks of ventilator support revealed the devastation that this disease can cause. Tetanus spores are found in high concentration in the soils of rural areas, especially where farm animals have grazed. Populations most at risk in the U.S. include under- or non-immunized elderly and immigrant populations. Barriers to immunization include patient and physician non-compliance, missed opportunity for immunization and concern over vaccine side effects. Targeting high-risk groups will enable primary care physicians to be more proactive in providing immunization, and thus in preventing prevention this disease. PMID- 11761653 TI - Diagnosis and treatment of Helicobacter pylori infection in children: a survey of WV primary care physicians. AB - Helicobacter pylori infection has been implicated in the development of peptic ulcer disease in children. Although clinical protocols for the diagnosis and treatment of this infection in children are available, the implementation of those guidelines by primary physicians are insufficient. In this study, we surveyed the clinical practices of 409 primary physicians who practice in West Virginia and treat children with H. pylori infection. Results showed in contradiction with the recommendation, primary physicians are still using serology as the preferred diagnostic method for this disease. Most of the physicians treat this disease with a combination of two antibiotics and anti-acid medication (H2 blockers or PPI) for at least one week. We conclude that an increase in knowledge of those guidelines among primary physicians may improve physicians' compliance with H. pylori guidelines. PMID- 11761654 TI - Billing procedures and reimbursement for palliative care consultations. PMID- 11761655 TI - Managing malpractice liability: tips to limit your risk. PMID- 11761656 TI - WV Department of Health and Human Services. Information for physicians: anthrax. PMID- 11761657 TI - [A study on the biological effects of exposure mobile-phone frequency EMF]. AB - Together with a growing number of cellular telephone users increases the interest in the effect of electromagnetic fields (EMF) emitted by them on live organisms. The surveys on subjective complaints of cellular telephone users carried out in Sweden, Norway, UK, USA, New Zealand and Australia showed that head ache is the major complain, and it is more pronounced with analogue than digital telephones. Apart from head ache, fatigue and general ill-being, muscular pains and nausea are reported. Human experimental studies reveal that EMF emitted by cellular telephones may be responsible for periodical increase in arterial blood pressure, changes in electric activity of the brain. However, no changes in secretion of cerebral pituitary hormones: adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), growth hormone, prolactin (PRL), lactogenic hormone (LH), follicle-stimulating hormone (FSH) and melatonine. The animal experimental studies indicated that exposure to EMF of the microwave frequency activates the endogenous opioid system in the brain, while the studies of the brain neurotransmitter activity have not produced univocal results, some of them showed decline, others increase in acetylcholinesterase activity. In vitro studies reveal that EMF even below maximum permissible levels may induce changes in the blood-brain permeability barrier and disorders in active transport of Na+, K+ ions and release of Ca++ ions by cellular membranes. The studies carried out thus far have not produced clear-cut results, but they indicate that EMF of the microwave frequency, including the frequency emitted by cellular telephones may be responsible for various measurable biological effects. It is essential to find out whether these effects may affect human health. PMID- 11761658 TI - [Is there any risk interaction between electromagnetic field generated by mobile phones and artificial pacemakers]. AB - Electromagnetic noise is rapidly increasing in the environment. Electromagnetic fields (EMF) originating from a variety of different sources have been shown to interfere with the function of implanted cardiac pacemaker. The authors present the effect of EMF generated by wireless telephones on different types of artificial pacemakers. In addition, instructions on safe use of mobile phones addressed to people with implanted artificial pacemaker are provided. PMID- 11761659 TI - [Effect of organic solvents on hearing organ]. AB - This paper reviews the studies of ototoxicity of organic solvents. Experimental and clinical studies show some harmful effects exerted on hearing organ by organic solvents, especially by toluene, xylene, styrene, carbon disulfide, n hexane and trichloroethylene. These chemicals may affect different levels of auditory pathways. When assessing these effects in industrial conditions, it is necessary to consider the noise activity and interactions between organic solvents and noise. Further research should focus particularly on one major question on whether workplace conditions free from exceeding hygiene standards of organic solvents are completely safe for workers. PMID- 11761660 TI - [Revised maximum admissible intensity (MAI) values for infrasonic noise in work environment]. AB - A short review of infrasound sources is presented. The measuring methods and occupational exposure limits for infrasonic noise (infrasound) are described. The amended Polish regulations on maximum admissible intensity (MAI) values for infrasonic noise in work environment and proposals of exposure limits for workers at particular risk (i.e. pregnant women and juveniles) are discussed. PMID- 11761661 TI - [Vanadium: threat and hope]. AB - Vanadium is an element classified in the group of heavy metals, very common in the natural environment and widely used in industry. It is mainly used in the production of nonferrous alloys, most resistant carbon steel, as well as in chemical, glass, paint and varnish, ceramic, and photographic industries. In the atmosphere, two second of vanadium originates from anthropogenic sources, sea born aerosols and volcanic eruptions. Municipal waste is the major source of vanadium in surface water. It is one of the components of live organisms and participates in many biochemical processes essential for their proper functioning, but in higher concentrations it may induce acute or chronic intoxication that damage biological structures and disorder biochemical systems. The mechanism of vanadium toxic effect has not as yet been elucidated, however, it is already known that this mechanism is rooted among others in vanadium properties able to hinder a number of enzymatic systems. For vanadium the most "critical" systems are respiratory, urinary and hemopoietic. Vanadium salts may also be genotoxic and harmful at different phases of reproduction and development. Numerous studies of a possible use of vanadium in treatment of certain diseases, e.g., diabetes, have been carried out. Some findings on a potential antineoplastic or contraceptive effect of vanadium compounds have recently been reported. To sum up, there are numerous hazards associated with the wide industrial use of vanadium, nevertheless, the number of findings highlighting its nutritive and therapeutic properties is growing. PMID- 11761662 TI - [Effect of fluorine compounds on metabolism of erythrocytes]. AB - The molecular mechanism for regulating nucleotide contents depends on the activity of numerous enzymes during glycolysis, pentose cycle and oxidation reduction system. Special attention was paid to the consequences of indirect effects of fluorine on ATP, ADP and AMP contents, nucleotide pool, energetic charge and the amount of 2,3 DPG. The effects of fluorine on ATP-ase activity are also described. PMID- 11761663 TI - [Problems in diagnosis of vibratory articular skeletal syndrome]. AB - Vibratory syndrome is still one of the essential problems in occupational health care. A literature review indicates that the majority of studies focus on vascular changes with very limited data on radiological articuloskeletal changes. Non-acute disease manifestation and the lack of clear-cut radiological criteria of skeletal changes contribute to diagnostic problems. The situation presented cannot be accepted as satisfactory in terms of certification consequences at the individual and population levels. There is a need to continue epidemiological studies which should allow for developing diagnostic criteria formulated in a simple way, as well as quantitative and qualitative rating of radiological skeletal changes. PMID- 11761664 TI - [Assurance and assessment of education quality in occupational hygiene in the United Kingdom, United States and Canada]. AB - There is an urgent need to develop and formally recognise the profession of occupational and environmental hygienist in Poland. A high quality of specialist training in occupational hygiene is a prerequisite for any successful action aimed at accomplishing this goal. Assurance and assessment of education quality in this domain is inseparably associated with the problem of accreditation and certification. The first difficulty lies in a limited number of patterns or points of reference, such as systems of accreditation and certification in the area of occupational hygiene that already function. Insufficient dissemination of knowledge of the systems which already exist and function properly is another difficulty. Based on the Anglo-Saxon literature dealing with this subject, the author tries to bridge this gap. PMID- 11761665 TI - [An opinion expressed in the discussion on the article entitled "Vocal disorders in students of teaching college"]. PMID- 11761666 TI - [Natural history of occupational allergy to latex in health care workers]. AB - The analysis of natural history of allergy to natural rubber latex (NRL) in health care workers, including the influence of exposure cessation on the clinical status and objective allergy markers was the objective of the study. The study covered 58 patients with recognised allergy to NRL. Of this number, 26 were followed up for 2 years after diagnosing NRL allergy. Medical examination, skin prick tests for common allergens and NRL, determination of total serum IgE and NRL-specific IgE antibodies, rest spirometry and non-specific bronchial hyperactivity test with histamine were performed. The retrospective analysis of clinical manifestation of NRL allergy revealed in 36% of patients progression of symptoms from local urticaria and rhinitis to systemic reactions. Two years after the cessation of exposure to NRL, symptoms became less severe in the majority of patients and even a clearance of allergic symptoms was observed, as well as the decrease in doses of inhalative glicocorticosteroids was noted. This was accompanied by the decline in non-specific bronchial hyperactivity. Although the skin prick tests showed the tendency to remain positive, the decrease in the level of specific anti-NRL IgE was found in 10 patients (including the RAST negativisation in one case). In conclusion, clinical progress from NRL-induced contact urticaria and allergic rhinitis to systemic reactions was observed only in part of patients with NRL allergy, which cannot be taken as a rule. Significant reduction of clinical symptoms or even total remission of NRL allergic symptoms could be observed after exposure cessation. PMID- 11761667 TI - [Sickness absence among workers with occupational locomotor system diseases]. AB - A long-term analysis of the data on temporary incapacity for work may be useful in identifying the most essential changes in the pattern of the causes of the disease-related incapacity for work and give the alert for taking necessary measures to protect the human health. The aim of the analysis is to define the causes of temporary incapacity for work prior to the diagnosis of chronic diseases of the locomotor system induced by the way the job is performed and the work overload in workers' groups of the highest disease incidence. The sickness absence study was carried out in the group of 395 workers with the locomotor system diseases due to the above-mentioned causes, diagnosed during the years 1996-1997. The analysis was based on numbers of days of work disability, numbers of cases and the average duration of disease. The rates of work disability days in the study group were compared with relevant rates in the occupationally active population of Poland. The analysis of sickness absence during a five-year period before the certification of the occupational diseases of the locomotor system revealed the sickness absence higher by 52% in male workers and by 60% in female workers than the average sickness absence in the general population. In this group, the diseases of the musculoskeletal system were the major cause of work disability, being responsible for 48% of sickness absence. The highest work disability was found in male workers with shoulder pain syndrome (about 49 days/person/year) and female workers with tenosynovitis and bursitis (45 days/person/year). As to the selected occupational groups, the first place was occupied by the group of workers engaged in metal processing (53 days/person/year), in which diseases of the musculoskeletal system made over 50%. In miners, besides locomotor diseases, a high level of sickness absence was due to the diseases of the nervous system and sense organs (17% of absence). In the group of dentists, the circulatory system diseases were the major cause of work disability in men (38% of absence), and the musculoskeletal system diseases in women (36% of absence). The study indicates that sickness absence can prove to be a substantial parameter that renders it possible to identify persons with enhanced risk of occupational disease by physicians involved in prophylactics and to take necessary preventive measures. PMID- 11761668 TI - [Radioisotopic diagnostic examination as a factor responsible for the Polish population exposure to ionizing radiation]. AB - For the general population, in vivo radioisotopic radiological examinations are the second, after x-ray diagnostics, artificial source of ionizing radiation used for medical purposes. The 1981 survey was the first review of the radioisotopic examinations in Poland and revealed that 80,000 examinations are performed annually (2 examinations per 1,000 population on average). It was also found that 131 I was the most common isotope used during thyroid examinations very frequently performed at that time. According to the 1996 data published by the National Consultant on Nuclear Medicine, "In Poland there are 36 centers of nuclear medicine within the network of public health care services. Every year about 130,000 radioisotopic examinations are performed." In order to estimate real exposure of the Polish population resulting from radioisotopic diagnostic examinations it is necessary to gather detailed data on the age structure of patients, as well as on the type and activity of radiopharmaceutical be administered. The paper presents the preliminary results of the follow-up study on radioisotopic examinations in Poland carried out by the Department of Radiological Protection, Nofer Institute of Medicine, Lodz. The data have been collected according to the adopted schedule, taking account of the organ (system) examined, the type of administered radiopharmaceutical, the kind and activity of radioactive isotopes used to mark radiopharmaceutics, age and sex of examined patient. By the end of December 2000 the data on radioisotopic examinations performed in 12 centers of nuclear medicine (Warsaw--7; Kielce--2; Gdansk, Lodz and Zgierz--one center in each city) had been collected. Thus far almost 40,000 radioisotopic examinations have been registered. According to the above mentioned procedure it was possible to collect data on all examinations performed in 1998. In addition, general numbers of examinations performed in the centers visited in 1999 were registered; the 2000 data are now being completed. It was finally established that the thyroid and musculoskeletal examinations constitute about 50% of the total number of examinations, which is in agreement with the data applying to the countries classified as those with the first level of health care. However, while an average effective dose per examination in those countries accounts for about 4 mSv, in the Polish centers the analogues indicator, estimated on the basis of the results collected thus far, is about 9 mSv, of this number, over 7 mSv is contributed by thyroid examinations with the use of iodine (131I). The obtained result is a strong stimulus to supplement and complete the data already gathered and to carry out a thorough analysis of radioisotopic examination in view of patients' exposure. Such an analysis would provide the subject matter arguments for the optimization of radiological protection in nuclear medicine in Poland. PMID- 11761669 TI - [Urinary trehalase activity as an indicator of renal dysfunction in lead smelters]. AB - Epidemiological and experimental studies have demonstrated that lead and cadmium are responsible for renal dysfunction. Urinary trehalase is known as a good marker of proximal tubular renal brush border destruction in the population environmentally exposed to cadmium. The aim of this study was to determine the impact of occupational exposure to lead on the renal function and urinary trehalase activity. The study was carried out in 68 workers, aged 46 +/- 6 years, employed in a copper foundry. Blood lead, cadmium, copper and manganese concentrations were measured by atomic absorption spectrophotometry. Urinary trehalase activity was determined by the method of Nakano and Itoh. Trehalase activity was increased in copper smelters as compared to controls. There also was a positive linear correlation between blood lead level and urinary trehalase activity (r = 0.44; p < 0.05). Negative correlations between blood lead and copper concentrations (r = -0.30; p < 0.05) and between serum copper and trehalase level (r = 0.68; p < 0.001) were found. The results show that urinary trehalase activity could be a good indicator of the renal brush border dysfunction in copper smelters. This marker could be useful in the early diagnosis of nephrotoxic effect of lead. PMID- 11761670 TI - [Renal dysfunction in chemical plant workers producing dust pesticides]. AB - The study covered workers of a chemical plant producing dust pesticides. A study group included 24 men, aged 29-54 years, employed directly in the production, and 22 women, aged 31-52 years, performing auxiliary jobs and handling only closed packages. In order to assess the renal function in the workers, the concentrations of serum creatinine and uric acid, protein, albumin and alpha 1 microglobulin, as well as the activity of alkaline phosphatase (AP) and N-acetyl beta-glucosaminidase (NAG) in urine were determined. The average air dust concentration at the workplaces was 0.42-16.66 mg/m3. The active substances with concentrations ranging from 10 to 75% in the final product were as follows: triazines, dithiocarbamates, carbendazim and thiophanate-methyl, captan, phenylureas, cupric oxychloride and occasionally also carbamates, dodine and 2,4 D. As compared to the results in the control groups of 31 healthy men and 22 women, free from occupational exposure to chemical noxas, a significantly higher serum creatinine concentration (in none of the subjects creatinine concentration exceeded the upper normal limit) and higher urinary protein, albumin and alpha 1 microglobulin concentrations, and higher enzyme activity were found in men, while in women only urine enzyme activity was significantly increased. The results speak in support of a discreet subclinical kidney impairment. PMID- 11761671 TI - [Validation of methods used for the assessment of the efficiency of selected psychophysical functions in gantry operators]. AB - The aim of the study presented was to develop psychological procedures useful for the replacement examinations of gantry operators. The psychological traits needed to ensure proper and safe handling of gantry were defined on the basis of work analysis. The experimental test battery for measuring these traits was worked out on the same basis. The group of 138 gantry operators, aged 19-59 years, were examined. Their test scores were used to estimate psychometric parameters of the test battery. The analysis of the results allowed to choose the best predictors of work capability. The authors also proposed the principles of the decision making process based on the test scores. PMID- 11761672 TI - [Risk of noise-induced hearing loss in farm tractor operators]. AB - Studies of noise at work site of tractor operators showed that this parameter exceeds allowable values. In order to evaluate the risk of hearing loss in this occupational group, noise-induced permanent threshold shift (NIPTS) values were determined. This parameter is a function of the audiometric frequency, duration of occupational exposure and noise exposure level (LEX,8 h). The procedure recommended by ISO-1999/1990 was used for calculations. The study covered two groups of operators: operators of ZM "Ursus" medium-power tractors (noise exposure level: LEX,8 h = 96.6 dB) and operators of high-power tractors of the same manufacture (LEX,8 h = 89.6 dB) The risk of hearing impairment was determined for the group of men aged 50 years, occupationally exposed to noise for a period of 30 years. The calculation was based on the mean value of expected hearing loss for three selected audiometric frequencies: 1000; 2000; and 4000 Hz. The study showed that the average (median; N0.50) expected hearing loss, excluding that associated with age, after 30 years of employment was 15 dB for operators of medium-power farm tractors, and 6 dB for operators of high-power tractors. The risk of hearing impairment due to occupational exposure to noise (exceeding the maximum allowable hearing loss of 27 dB; according to ISO 1999/1990) that may cause an acoustic trauma was 37.9% for medium-power tractors and 13.0% for high-power tractors. The results of the study show that noise at workplaces of farm tractor operators creates a high risk of hearing impairment. PMID- 11761673 TI - [Changes in the state of air ionization caused by medical equipment]. AB - The author discusses the effect of the ion-emitting medical equipment on changes in the air-ions concentration. The study shows that in the majority of cases (except for cobalt bomb) the changes observed fall within the range of the binding norms. PMID- 11761674 TI - [Human immunodeficiency virus in the work environment]. AB - This paper addresses the problem of occupational risk assessment of HIV infections and presents current data on HIV prevention. The risk of HIV infection is much lower than the probability of other infectious diseases that create an important medical problem in Poland. Nevertheless, it is a real hazard, involving not only medical, but also psychological, educational and social aspects. As yet there has been no documented case of occupational HIV infection in Poland, but health care workers should be aware of the HIV infection risk and should apply all possible preventive measures. PMID- 11761675 TI - [The role of vibration in pathology of hearing]. AB - Vibration is now considered as one of the most common environmental traumatic factors. The energy absorbed may exert a pathological effect on all bodily tissues and organs, although the consequences of exposure to vibration do not present a uniform clinical picture. Because all machines and vibrating tools also produce noise, the combined effect of both factors is usually examined. In the professional literature, an opinion predominates that vibration exerts only a week, additional traumatic influence on the hearing organ. This opinion is contrary to reports on vibration-related hearing impairments observed in workers of various branches of industry. In the past, the studies of harmful effects of vibration with the participation of volunteers were seldom and short-term. Experiments on laboratory animals were carried out on species with different sensibility of the hearing organ, and exposure to vibration was most frequently accompanied by noise. Nevertheless, they usually confirmed the presence of vibration-related changes in the inner ear, mostly in the hair cells. Moreover, there have been several reports on post-vibratory pathological changes not only in the inner, but also in other parts of the ear. All these findings indicate that the role of vibration in the pathology of the hearing organ is still underestimated and not fully elucidated. PMID- 11761676 TI - [Is the order of the Minister of Health of May 5, 2001 a mistake?]. PMID- 11761677 TI - [Hemorrhagic cystitis: etiology and treatment]. AB - Haemorrhagic cystitis consists of acute or insidious diffuse bleeding from the bladder mucosa. Although the aetiology of haemorrhagic cystitis is varied, the two predominant causes are chemical and irradiation. The chemical compounds most frequently responsible for haemorrhagic cystitis are oxaphosphorines (cyclophosphamide, ifosfamide). Haemorrhagic cystitis may also be due to toxic or infectious causes (bacterial, fungal, parasitic or viral). Finally, haemorrhagic cystitis can occur in the context of a systemic disease or may be isolated and idiopathic. Prevention of haemorrhagic cystitis, based on general measures and specific measures, is essential, but is not always effective. In the case of proven haemorrhagic cystitis, various treatment options are available, including and can associate clot extraction, continuous bladder irrigation, bladder instillations of haemostatic factors, formalin, hyperbaric oxygen therapy, arterial embolization or salvage surgery. Although therapeutic management is usually effective, it can sometimes be difficult due to the severity of the bleeding and its repercussions on the patient's general state. Deaths are not exceptional, emphasizing the seriousness of haemorrhagic cystitis. Based on a review of the literature, the authors review the aetiology and treatment of haemorrhagic cystitis. PMID- 11761678 TI - [Diagnostic methods for obstruction of the upper urinary tract: which tests are available in 2001]. AB - The presence of upper urinary tract obstruction, its site and its nature can be determined and the most appropriate treatment can be defined in the majority of clinical cases. However, in some circumstances, non-invasive or minimally invasive methods, such as ultrasonography, intravenous urography, urography with diuretic test, conventional and diuretic nephrography and MR urography, are unable to confirm the presence of obstruction, requiring assessment of the upper urinary tract by antegrade pyelomanometry. This investigation measures the pressure in the upper urinary tract perfused at a constant rate by a percutaneous catheter and allows evaluation of the obstruction. The authors discuss the place of the various upper urinary tract investigations to confirm the definitive diagnosis of upper urinary tract obstruction. PMID- 11761679 TI - [Idiopathic male infertility and androgen receptors]. AB - In France, 12 to 15% of couples experience procreation difficulties. A disorder of spermatogenesis (oligospermia, azoospermia) is responsible in 1/3 of cases. These forms of infertility, labelled idiopathic, probably have a genetic component, like microdeletions of the Y chromosome. The normal rate of circulating androgens suggests the implication, in some cases, of an abnormality from the receptor to the androgens (RA) of these male infertilities, whose number remains to be defined. Point mutations on exons of the gene encoding the AR cannot account for all cases of infertility due to idiopathic disorders of spermatogenesis. Expansion of the number of CAG triplets of exon 1 of the AR gene, already demonstrated in a fatal degenerative neuropathy (Kennedy's disease, in which more than 50% of patients are infertile), has been detected in these cases of idiopathic infertility and would be responsible for AR dysfunction. The number of these triplets is also decreased in patients with androgen-dependent prostate cancer. The polymorphism of repetition of CAG triplets would therefore be responsible for fine adjustment of the AR between excessive and insufficient function. ICSI. (Intra-Cytoplasmic Sperm Injection) is currently proposed in these cases of infertility, but the consequences of transmission of these abnormalities to the offspring are unknown. PMID- 11761680 TI - [Systematic conservative surgery for kidney cancer smaller than 4 cm: multicenter study]. AB - OBJECTIVE: To evaluate tumour control and morbidity of systematic conservative surgery for patients with a renal cancer < or = 4 cm. MATERIALS AND METHODS: A retrospective multicentre study was performed in 73 patients undergoing systematic conservative surgery for renal cancer < or = 4 cm. The mean age of the patients was 55.8 years (range: 19-82). The mean diameter of the tumour was 2.8 cm +/- 0.9. Tumour stage was pT1 in 97% of cases and pT3a in 3% of cases. The mean follow-up was 46.2 months (range: 12-138). RESULTS: The postoperative morbidity was 11%, including urinary fistulas in 5 cases and haemorrhage in 3 cases. No patient has developed local recurrence. One patient died from metastases. The 5-year recurrence-free survival was 97.4%. CONCLUSION: Systematic partial nephrectomy has a low morbidity in patients with a renal cancer less than 4 cm. It ensures satisfactory medium-term tumour control. However, only long-term follow-up can establish the place of systematic partial nephrectomy in the treatment of renal cancer. PMID- 11761681 TI - [Retroperitoneoscopic pyeloplasty for primary hydronephrosis: preliminary results of the first 30 procedures]. AB - OBJECTIVE: To evaluate the preliminary results of retroperitoneoscopic pyeloplasty (RP) for the treatment of primary ureteropelvic junction syndrome (PUPJS) in terms of operating time, operative and postoperative complications, clinical functional and radiographic results, length of hospital stay and resumption of physical activity. MATERIAL AND METHODS: From November 1997 to June 2000, from a consecutive series of 59 patients treated for an anomaly of the ureteropelvic junction (UPJ), the 29 patients (18 females and 11 males, mean age: 35.6 years [range: 17-68]) operated by RP for PUPJS (bilateral in one case) were reviewed. Twelve patients presented a lower pole vascular pedicle and 24 patients had an extrasinusal renal pelvis. The RP technique was identical for all patients (4 ports) and the UPJ repair was performed according to the technique described by Anderson-Hynes and Kuss (28 cases) or Y-V plasty (2 cases). RESULTS: The mean operating time was 150 minutes (range: 120-240) and the mean hospital stay was 4.2 days (range: 3-10). There were no intraoperative complications, but one conversion (3.3%) was necessary because of major adhesions. postoperative complications (23.3%) consisted of: four urinary tract infections with one case of acute pyelonephritis, perirenal haematoma, urine leak in the Redon drain due to obstructed double J stent, migration of the double J stent underneath the anastomosis leading to unstentable cicatricial stricture (treated by open pyeloplasty 3 weeks later). With a mean follow-up of 19.7 months (range: 7-40), 28 patients were asymptomatic and one patient presented persistent lumbar pain at 9 months with no signs of recurrence. The 3-month IVU, performed in 27 patients, showed reduction of hydronephrosis in 85.7% of cases and a patent ureteropelvic junction in 96.3% of cases. Complete resumption of physical activity and return to work were possible an average of 1 month postoperatively (a fortnight for the population under the age of 40 years). CONCLUSION: PUPJS can be treated by RP according to the same principles as conventional surgery. RP pyeloplasty can be performed with an acceptable operating time and morbidity. The functional and radiological results in terms of patency of the UPJ need to be assessed in the longer term. PMID- 11761682 TI - [Kidney cooling during multi-organ harvesting. Descriptive study]. AB - OBJECTIVE: To describe kidney cooling during multi-organ harvesting (MOH) from brain-dead donors and to evaluate harvesting practices. MATERIAL AND METHOD: The temperature of 12 kidneys (6 left and 6 right kidneys) was monitored continuously during MOH from brain-dead donors. After in situ cooling, the kidneys were separated on the table and washed for several minutes with UW preservation solution. The kidney temperature was studied as a function of the main phases of the operative procedure. RESULTS: The mean minimum kidney temperature of 10.8 degrees C (3.7 degrees C to 16.6 degrees C) was reached at the beginning of mobilization of the liver, i.e. an average of 20 minutes (13 to 37 min) after cannulation. The mean cooling rate was 1.37 degrees C/min (0.73 to 2.19 degrees C/min). The mean temperature of the UW cooling solution was 9.4 degrees C (3.8 degrees C to 14 degrees C). For hepatic followed by renal dissection, the kidneys slowly reheated at a mean rate of 0.20 degree C/min (0.12 to 0.37 degree C/min) to reach a mean temperature of 21 degrees C (13.5 degrees C to 26.3 degrees C) at the time of resection. The mean kidney temperature at the time of placement in the container was 17.5 degrees C (13.2 degrees C to 22 degrees C). CONCLUSION: The course of kidney temperature during MOH has not been previously described. This study, performed under usual harvesting conditions, demonstrated sometimes imperfect cooling that could be harmful to he kidneys, but which could be improved by simple measures: rapid dissection of the liver and kidneys and correct application of contact cooling. PMID- 11761683 TI - [Substitutive non-modeled uretero-ileoplasty]. AB - OBJECTIVES: To evaluate the indications and results of replacement uretero ileoplasties performed over the last six years. MATERIAL AND METHODS: Over a period of 6 years, 8 patients underwent subtotal or total replacement uretero ileoplasty involving a total of 9 renal units. Preoperative temporary urinary diversion was performed in each patient. The mean preoperative serum creatinine was 88 mumol/l (range: 53 to 150). Uretero-ileoplasty was performed for ureteric stricture in 7 cases (bilateral in one case and in a solitary kidney in one case), ureteric necrosis following renal transplantation without a donor ureter in one case and urothelial tumour on a solitary kidney in one case. RESULTS: The mean follow-up was 54 months. The mean operating time was 218 minutes for uretero unilateral ileoplasties, with a mean length of hospital stay of 12 days (range: 10 to 18 days). The following complications were observed: acute urinary retention, stenosis of the ileo-vesical implantation treated by endoscopic dilatation, 2 incisional hernias after midline laparotomy, one case of stones of the ileo-vesical anastomosis, non-febrile urinary tract infections treated on an outpatient basis. The functional result was considered to be satisfactory in every case. No electrolyte disorders were observed. Mean postoperative serum creatinine was 86 mumol/l (range: 59 to 140). CONCLUSION: In this recent series with a mean follow-up of 4.5 years, replacement uretero-ileoplasty successfully treated partial or total complex ureteric lesions with a low morbidity. PMID- 11761684 TI - [Urologic management of ureteral iatrogenic lesions]. AB - INTRODUCTION: Iatrogenic trauma of the ureter can occur following pelvic, abdominal or retroperitoneal surgery and during laparoscopy or ureteroscopy. MATERIAL AND METHODS: From 1988 to 1998, 30 patients with 34 iatrogenic ureteric injuries were treated in our department. RESULTS: Patients were referred after a mean of 13 days. Endourological treatment was performed as first-line management in 76% of cases of ureteric trauma, with a 71% immediate success rate. In the case of failure, surgery was performed in 78% of cases, with an 83% success rate. Seven patients required nephrectomy and one patient died. CONCLUSION: First-line endourological treatment gives good results. An early diagnosis remains an essential prerequisite to avoid serious complications. PMID- 11761685 TI - [Tolerance and efficiency of intravesical instillation of Calmette-Guerin in the prophylactic treatment of superficial bladder tumors, using a maintenance treatment]. AB - Maintenance treatment with complementary BCG instillations in the prevention of superficial bladder tumour could improve the results of this immunotherapy. This maintenance treatment is limited by accentuation of the adverse effects related to BCG. OBJECTIVES: To evaluate the impact of maintenance treatment on tumour recurrence and progression, and to evaluate the influence of adverse effects on maintenance treatment and the recurrence rate. MATERIAL AND METHODS: 72 patients were treated with six weekly instillations of 81 mg of BCG (Immucyst) followed by three complementary instillations 3, 6, 12, 18, 24, 30 and 36 months later. Adverse effects (AE) were classified into four classes, according to their type, severity and duration, and were recorded prospectively for 518 instillations. An adverse effect score was determined for each patient. RESULTS: 84.9% of patients did not present any recurrence, 12.5% developed recurrence and 2.6% progressed. The instillation regimen was completed by 19% of patients, the dose had to be decreased for 57% of patients and treatment had to be discontinued for 39% of patients. An initial adverse effect score (AESi) greater than 1.5 was associated with an increased risk of discontinuation of treatment or reduction of the dosage during maintenance treatment (p = 0.01). CONCLUSIONS: Maintenance treatment was associated with a very low recurrence and progression rate. We have established and validated an adverse effect severity scale and the consequences of these adverse effects on maintenance treatment. This scale could be used to prospectively define the most appropriate maintenance instillation regimen, by preventively decreasing the doses or deferring instillation. PMID- 11761686 TI - [Role of complementary tests in the management of colo-vesical fistulae]. AB - OBJECTIVE: Colo-vesical fistulas (CVF) are a complication of inflammatory or neoplastic diseases of the lesser pelvis. Although the clinical diagnosis is obvious in the presence of pneumaturia or faecaluria, a number of patients require complementary diagnostic and/or pretreatment investigations. The objective of this study was to analyse the management of these patients in order to define the place and cost-effectiveness of complementary investigations. MATERIAL AND METHODS: This retrospective study was based on 37 patients with a colo-vesical fistula, secondary to sigmoid diverticulitis in 60% of cases. RESULTS: Cystoscopy was the most cost-effective examination for the diagnosis of CVF with a sensitivity of 94%. The preoperative assessment of CVF and the underlying disease was optimally performed by a combination of cystoscopy, opaque enema and CT. CONCLUSIONS: Our study defined the place of the various examinations in the assessment of colo-vesical fistula, but the value of magnetic resonance imaging, not performed in this series, remains to be defined. PMID- 11761687 TI - [Stage T1a prostatic cancer: long-term retrospective study of 27 patients]. AB - OBJECTIVE: The natural history of stage T1a prostate cancer is generally favourable, but is nevertheless associated with a considerable progression rate of 7% to 27% depending on the study. The objective of this study was to identify possible predictive criteria of tumour progression to improve patient surveillance and early treatment. MATERIAL AND METHODS: 27 patients with stage T1a prostate cancer according to the TNM 97 classification, were followed for a mean duration of 79 months (range: 24-132, median: 68). A complementary assessment was performed in patients under the age of 70 years, and a strict clinical (DRE) and laboratory (PSA) surveillance protocol was performed in all patients. The initial mean PSA was 7 ng/ml and the mean Gleason score was 4.8. RESULTS: 20 patients (75%) did not present any clinical and/or laboratory signs of progression and were therefore not treated. Seven patients (25%) received treatment with a mean follow-up of 63 months (radical prostatectomy in 2 cases, external beam radiotherapy in 1 case, endocrine therapy in 4 cases). All patients are alive and in complete remission at last follow-up. CONCLUSION: Based on our results and a review of the literature, conservative management based on strict, long-term surveillance, is a frequent approach to stage T1a prostate cancer confirmed by negative biopsies of the residual capsule. The PSA velocity is the key to surveillance, and the only factor of predictive of tumour progression that can be really used in routine clinical practice. However, our study showed tumour progression in 25% of cases, raising the question of curative treatment, especially in young patients. PMID- 11761688 TI - [Hypospadias in adults]. AB - INTRODUCTION: In order to evaluate the long-term results and complications, the authors reviewed the files of 14 adult patients operated for the first time for hypospadias. MATERIAL AND METHODS: This study was based on retrospective analysis of the files of 15 adults between the ages of 17 and 36 years operated for hypospadias between 1989 and 1999. The findings of the first visit concerned the site of the urethral meatus, the presence and severity of chordee and the primary and secondary sexual characteristics. Urine culture was performed in all patients. RESULTS: The follow-up was 12 months to 8 years. Six of the 15 patients were treated by urethroplasty alone and 9 patients underwent urethroplasty with correction of chordee. 40% of patients (3 cases of anterior hypospadias, 2 cases of midpenile hypospadias and 1 vulviform hypospadias) obtained a good long-term result. In the case of complications (fistula, stenosis or distal necrosis of the tube), a single reoperation allowed good results to be achieved in 80% of the series. CONCLUSION: The results of treatment of hypospadias in adult patients differ from those obtained in children despite the use of similar surgical techniques. PMID- 11761689 TI - [Renal metastasis of thyroid carcinoma]. AB - The authors report a case of renal metastasis from a follicular carcinoma of the thyroid in a 62-year-old man, occurring 7 years after isthmolobectomy for thyroid carcinoma. Clinical symptoms radiographics results and treatment are discuss after a review of the literature. PMID- 11761690 TI - [Pheochromocytoma discovered in the preoperative period: analysis of 3 cases]. AB - Phaeochromocytoma is a rare tumour that may be discovered incidentally during a surgical operation that can sometimes cause fatal arrhythmias. The authors report 3 cases of phaeochromocytoma presenting in the form of hypertensive crisis and serious arrhythmias following manipulation of the tumour with a fatal outcome in 2 cases. These cases illustrate the severity and complexity of the problems encountered and the importance of preoperative detection of phaeochromocytomas, particularly at the pre-anaesthetic visit. PMID- 11761691 TI - [Paraganglioma associated with gastric schwannosarcoma]. AB - The authors report the case of a 45-year-old patient who presented with a left latero-aortic paraganglioma associated with gastric schwannosarcoma. Treatment consisted of resection of the chromaffin tumour and the gastric tumour, with a favourable course at last follow-up. The authors review the literature on this subject. PMID- 11761692 TI - [Complex tubercular ureteral stenoses (report of 2 cases treated with permanent double-J catheter]. AB - Two patients presenting complex tuberculous ureteral strictures on an only existing kidney were treated with definitive double J stent changed every 6 months. This treatment modality was well tolerated. On the basis of two cases and literature review, different therapeutic measures are discussed. PMID- 11761693 TI - [Seminal vesicle cyst associated with ipsilateral renal agenesis]. AB - The seminal vesicle cyst associated with ipsilaterale renal agenesis is a rare entity. Through this case report, we analyse the clinical aspects, the importance of imaging techniques and the various therapeutic possibilities. The patient, age 24, presented perineal pain accentuated at ejaculation. The digital rectal examination showed a pre-rectal lump. Transrectal ultrasound plays an important role both for the diagnosis and the treatment. The treatment was perineal aspiration under transrectal echography control. The follow-up was satisfactory. CONCLUSION: The seminal cyst with ipsilareral renal agenesis is a rare congenital malformation, transrectal ultrasound is an excellent imaging technique for diagnosis, the perineal aspiration of the cyst constitutes a therapeutic alternative. PMID- 11761694 TI - [Urachal adenocarcinoma]. AB - Cancer of the urachus is very unusual. The lesion is a mucosecretory adenocarcinoma. The diagnosis is usually established late, and has a serious prognosis because of a long clinical latency. We report a case of metastatic adenocarcinoma of the urachus revealed by hematuria. A review of the literature allows us to demonstrate the rarity of this tumour and to demonstrate its various clinical, histological, radiological and therapeutical aspects. PMID- 11761695 TI - [Verrucous epidermoid carcinoma of the bladder unrelated to schistosomiasis]. AB - The authors report two cases of papillomatous squamous carcinoma of the bladder unrelated to schistosomiasis. Both patients were treated by endoscopic resection. The staging assessment comprised thoraco-abdominopelvic computed tomography. A papillomatous squamous carcinoma of the bladder was detected in both cases: one was classified as pT2 G1 N0 M0 and the other as pT1 G1 N0 M0. Recurrence was rapidly observed, at the first follow-up cystoscopy. The tumour initially classified as pT1 subsequently underwent transformation to sarcomatoid carcinoma with peritoneal metastases. Papillomatous squamous carcinoma of the bladder, a rare squamous cell carcinoma, is a well differentiated tumour with an exclusively local and regional development. The prognosis is determined by the degree of tumour invasion, with a high local recurrence rate. The prognosis of invasive tumours is identical to that of conventional squamous cell carcinoma. Therapeutic management is poorly defined, but the only curative treatment appears to be radical cystectomy. PMID- 11761696 TI - [Colonic pseudo-obstruction disclosing bladder calculi: report of 2 cases]. AB - The authors report two cases of acute intestinal obstruction caused by bladder calculi and insist on differential clinical diagnosis. Simple X ray and sonography seemed to be sufficient-for diagnosis of this extrinseque colique obstruction and management consisted of removal of the bladder stones The prognosis is excellent. PMID- 11761697 TI - [Emphysematous pyelonephritis: report of 3 cases]. AB - Emphysematous pyelonephritis (EPN) is a rare form of renal suppuration defined by the presence of pus and gas or bacterial origin within the renal parenchyma. It is associated with a high mortality in the absence of rapid and effective treatment. Emergency nephrectomy constitutes the reference treatment. Percutaneous drainage associated with medical treatment is an alternative in patients with localized or bilateral lesions or in the case of solitary kidney. The authors report 3 cases of EPN treated by percutaneous drainage combined with medical treatment for a localized lesion in two cases and nephrectomy in one case of disseminated multilocular lesion with an uneventful course in all three cases. PMID- 11761698 TI - [Malformations of male genital organs]. PMID- 11761699 TI - [Organogenesis of male genital tract]. PMID- 11761700 TI - [Anomalies of mullerian origin in men and prostatic anomalies]. PMID- 11761701 TI - [Anomalies of the male internal genital organs and their impact on fertility]. PMID- 11761702 TI - [Malformations of male internal genital organs originating from the Wolff mesonephrotic canal]. PMID- 11761703 TI - [Current approach to hypospadias in children]. AB - Hypospadias surgery has dramatically changed over the last 15 years with a new anatomical approach of the ventral penile anomalies and new techniques of repair. The description of the hypoplasia of the tissues forming the ventral aspect of the penis (ventral radius of the penis) beyond the division of the corpus spongiosum, and the concept of urethral plate are the two key-elements to select the most appropriate technique of reconstruction. These modern concepts and the various surgical techniques used are reported here with their results. PMID- 11761704 TI - [Laparoscopic treatment of symptomatic calculous diverticulum of the calyx]. AB - Treatment of urinary stones in a caliceal diverticulum may be indicated when they are symptomatic. Operative techniques for the kidney are continuing to improve. After open surgery and percutaneous surgery, laparoscopy occupies an increasingly important place in the urological therapeutic armamentarium over recent years. The authors report the case of a woman with a stone in an inferior caliceal diverticulum, discovered in the context of acute pyelonephritis, and effectively treated by transperitoneal laparoscopy. The details of the operative technique are described and discussed in relation to the techniques reported in the literature. PMID- 11761705 TI - [Eunuchism in Byzantium]. AB - The purpose of this article is to present the various types of eunuchs, the castration techniques and the modification observed on males due to castration. PMID- 11761706 TI - [Re: "Usefulness of p53 in the clinical management of bladder tumors", by S. Bernardini, E. Chabannes, H. Bittard. Prog. Urol., (2001), 11, 201-208]. PMID- 11761707 TI - [Re: "Endoscopic treatment of vesico-renal reflux in children: short- and long term results of polytetrafluoroethylene (Teflon) injections" by P. Chaffange, R. Dubois, A. Boyhafs, A.F. Valmalle, H. Dodat. Prog. Urol., 2001, 11, 546-551]. PMID- 11761708 TI - The TATA-less promoter of VP1, a plant gene controlling seed germination. AB - Vp1 is a seed-specific gene involved in the control of dormancy and germination. We here present the complete sequence of the sorghum vp1 promoter/enhancer region highlighting its main features, especially the lack of canonical TATA and CAAT boxes and the presence of elements responsive to abscisic acid and light. The region closest to the start of transcription is highly homologous to the partial proximal sequence reported for the maize vp1 promoter. This region is interrupted by a 57-nt stretch containing 14 CT microsatellite repeats. We observed a poor overall homology to the promoter from abi3 gene, the Arabidopsis counterpart bearing a similar coding sequence. However, there exists a high degree of homology (89%) between a TATA-rich 103-bp stretch of the sorghum vp1 promoter located about 700 nt upstream of the startpoint and miniature inverted transposable elements (MITEs) interspersed within the sorghum seed-specific kafirin cluster. This sorghum MITE-like element displays considerable homology (68%) to the TATA-less promoter from the sorghum NADP-malate dehydrogenase gene and lesser similarity to the Tourist, Pilgrim and Batuta MITEs previously identified within the promoter from the maize Abp1 (auxin-binding protein) gene. PMID- 11761709 TI - ADP-ribosylating binary toxin genes of Clostridium difficile strain CCUG 20309. AB - The cdt genes that encode a binary ADP-ribosylating toxin in Clostridium difficile were first characterized from a toxigenic C. difficile strain CD196 in 1997. We report here C. difficile strain CCUG 20309 (ATCC 8864), a strain that produces toxin B but not toxin A, also carry a complete set of cdtA and cdtB genes. These genes were sequenced by cycle sequencing method. The 2 ORFs and the intergenic sequences of these 2 strains have a homology of 99.6%. Interestingly, 9 extra bases were found within the cdtA gene of strain CCUG 20309 which do not affect the downstream region of the ORF. Using the same homologous primers, the highly toxigenic reference strain VPI 10463 was found to carry only parts of the 2 ORFs while a nontoxigenic strain ATCC 8884 does not carry any of the cdt genes. Though it remains to be determined whether these genes are expressed, it is significant that strain CCUG 20309 contains the complete set of cdt genes. We speculate that the putative expressed proteins may contribute to pathogenesis, for example, enterotoxicity, of this unique strain of bacteria. PMID- 11761710 TI - Isolation of a member of ets gene family in the polychaete annelid Perinereis cultrifera. AB - Numerous genes belonging to the ets gene family have been described for a few years. The founder of this family is the v-ets proto-oncogene, which is the viral counterpart of the chicken c-ets-1 proto-oncogene. Main research was carried out both on Vertebrates, Drosophila and the nematod Caenorhabditis elegans. Previously, two genes of this family named Nd ets and Nd erg, were isolated in the polychaete annelid Hediste (Nereis) diversicolor. Here we have described the isolation of one gene from the ets family in another polychaete annelid named Perinereis cultrifera. By polymerase chain reaction using degenerated primers, we have amplified an approximatively 515 pb genomic region encoding the ETS domain and another domain designed as "R" domain by Qi et al. (1992) and which can mediate transactivation. By using this method for isolating members of the ets gene family, we are going to realize a phylogenetic study of the phylum of polychaete annelids. PMID- 11761711 TI - Genetic divergence in the algT-muc operon controlling alginate biosynthesis and response to environmental stress in Pseudomonas syringae. AB - The algT-muc gene cluster (rpoE operon) is important for alginate production and survival during environmental stress in Pseudomonas syringae. The algT-muc operon was cloned and sequenced from P. syringae to determine whether the organization of this gene cluster was conserved in this plant pathogen. Interestingly, analysis of the algT-muc region in P. syringae revealed a unique arrangement when compared to other bacteria and lacked a mucC homologue. The relative importance of the mucC gene in the algT (rpoE) operon of various bacterial species is discussed. PMID- 11761712 TI - Structure of the mouse calcitonin/calcitonin gene-related peptide alpha and beta genes. AB - We report the cloning, genomic organization and sequence of the mouse alpha-CALC and beta-CALC genes. The two genes share extensive sequence homology. The transcription units of both genes contain 6 exons. Transcripts of the alpha-CALC gene were found to alternatively include exon 4 or exons 5 and 6. For the beta CALC gene exon 4 was not detected in transcripts derived from this gene. The predicted mouse alpha-CGRP was found to be identical to rat alpha-CGRP, however, beta-CGRP predicted amino acid sequences revealed three amino acid differences suggesting these residues are not critical to CGRP function. PMID- 11761713 TI - Characterization of a cadmium-inducible isoform of pyruvate carboxylase from Caenorhabditis elegans. AB - A homologue of pyruvate carboxylase was isolated as an expressed sequence tag during the identification of cadmium-responsive genes in Caenorhabditis elegans. The C. elegans protein, designated PYC-1, is predicted to contain 1,175 amino acids with a molecular mass of 129,284. Amino acid sequence analysis indicates that PYC-1 will be translocated into mitochondria. PYC-1 has high levels of amino acid sequence identity with other pyruvate carboxylases. The highest levels of identity are in the putative transcarboxylation, biotin carboxylation and biotin carboxyl carrier domains. PMID- 11761714 TI - Cloning, mapping and expression analysis of C15orf4, a novel human gene with homology to the yeast mitochondrial ribosomal protein Ym130 gene. AB - We have identified C15orf4, a novel human gene showing homology to the yeast mitochondrial ribosomal protein YmL30. C15orf4 encodes a transcript of 1,006 nt with an ORF of 279 amino acids and a predicted protein size of 31.7 kDa. Expression of C15orf4 is enriched in testis. C15orf4 was positioned to chromosome 15q24 by radiation hybrid mapping. We have identified the C15orf4 mouse orthologue as well as homologues in other species. PMID- 11761715 TI - Cloning and characterization of 5'-upstream sequence of the M32 gene for a mouse homologue of Drosophila heterochromatin protein 1 (HP1). AB - M32 [also termed chromatin modifier protein 2 (MOD2)] is a nuclear protein consisting of the condensed chromatin structure (heterochromatin) and considered one of the mammalian homologues of heterochromatin protein 1 (HP1), first isolated as one of the components of heterochromatin in Drosophila. This report presents the isolation and characterization of the 5'-upstream region of the mouse M32 gene containing a promoter region and 5'-untranslated region (5'-UTR) exon. The 5'-upstream region (approximately 0.27 kb starting from the 5' end of the 5'-UTR exon) of the M32 gene contained neither a TATA box nor a CCAAT box, but possessed potential binding sites for transcription factors such as Sp1, H4TF 1, PEA2, PEA3, GSG element and Egr-1, and was highly G/C-rich. The promoter activity of this 5'-upstream region was demonstrated by transfecting its fusion construct with the E. coli beta-galactosidase gene into the F9 mouse teratocarcinoma cell line. The 5' ends of the mRNA were mapped to at least two positions in the 5'-upstream region. Interestingly, the 5'-upstream region exhibited a high degree of similarity to a portion of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 gene, which is thought to play a role in RNA processing, located in the reverse orientation to the M32 gene, and also to several known ESTs and cDNAs. These findings suggest that the 5'-upstream region of the M32 gene consists of a multiple regulatory complex which probably plays important roles in nuclear function such as chromatin organization and RNA processing. PMID- 11761716 TI - Distribution of cerebral cortical lesions in Pick's disease with Pick bodies: a clinicopathological study of six autopsy cases showing unusual clinical presentations. AB - We investigated six Japanese autopsy cases of Pick's disease with Pick bodies (PDPB) both clinically and pathologically, and examined the distribution of their cerebral cortical lesions using hemisphere and/or bisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Two patients with a clinical diagnosis of primary progressive apraxia and of slowly progressive aphasia had speech apraxia as their initial signs, and the other two patients were suspected as having Alzheimer's disease, with the clinical diagnosis of the remainder two patients being presenile dementia and depression, respectively. Extrapyramidal signs, believed to be rare in PDPB, were present in four patients. Severe lesions were multicentrically present in the cerebral cortices of all six cases. In two patients with speech apraxia, severe lesions were seen in the primary motor area, which generally has not been regarded as an "atrophic center" in Pick's disease. Furthermore, in a patient with depression, severe lesions were more widespread in the convexity than in the orbital region of the frontal lobe. The parietal lobes, including the postcentral gyrus usually believed to be spared in Pick's disease, were severely involved in three patients. We postulate that the clinical features of PDPB have a much wider spectrum than previously believed. In addition, we believe that the distribution of the cerebral cortical lesions in PDPB is more widespread than previously assumed, and that clinical manifestations of PDPB depend to some extent on the topographic distribution of the cerebral cortical lesions. PMID- 11761717 TI - Temporospatial relationship between the expressions of superoxide dismutase and nitric oxide synthase in the developing human brain: immunohistochemical and immunoblotting analyses. AB - To clarify a significant relationship between superoxide dismutase (SOD) and nitric oxide synthase (NOS) in the developing human brain temporospatially, we demonstrate immunohistochemical expression of Cu/Zn-binding SOD1 (SOD1), Mn containing SOD2 (SOD2), neuronal NOS (nNOS), inducible NOS (iNOS), and nitrotyrosine in human brains from 13 weeks of gestation to 2 years after birth. The immunoreactivities of both SOD1 and SOD2 were detected in fetal neuroblasts at 13 weeks' gestation, as well as mature neurons at the age of 2 years. By contrast, nNOS neurons could be recognized only at 28 and 33 weeks of gestation in the cerebrum, and only at 15, 18, and 23 weeks of gestation in the brain stem. No significant immunoreactivity for iNOS or nitrotyrosine was detected in any type of cell in any region during any stage examined. Immunoblotting analysis using frontal tissue homogenates at 15, 28, 40 weeks of gestation and 18 months of age revealed single band corresponding to SOD1 molecular weight, observed at all stages examined; a single band compatible with the nNOS molecular mass was detected only at the 28th week of gestation. Together with the fact that nitric oxide (NO) plays a potential role in neuronal differentiation, and that large amounts of NO have cytotoxicity from the reaction of NO with superoxide anions, our data suggested that the expressions of both SOD1 and SOD2, as scavengers of superoxide anions, were maintained from an early developmental stage to prepare stage-specific nNOS expression for a potential differentiation role and to elude NO cytotoxicity. PMID- 11761718 TI - In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man. AB - Using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labelling (TUNEL) histochemical technique, evidence for DNA fragmentation was sought in the hippocampus, cingulate gyrus and insula from 18 patients who survived for up to 12 months after head injury, and 15 matched controls. Both conventional (haematoxylin and eosin and Luxol-fast blue/cresyl violet) and immunohistochemical (glial fibrillary acidic protein, CD68) staining techniques were used to identify the cellular response and its time course in the regions of interest. Only the occasional TUNEL-positive (+) cell/unit area was seen in any area of the control brains. In contrast there were more TUNEL+ cells/unit area in the injured brains. TUNEL+ cells were present in white matter and their average numbers ranged from three to five per unit area for up to 3 months survival in the extreme capsule and the parasagittal white matter, with similar numbers in the hippocampus, and between two and three per unit area in the parasagittal white matter and hippocampus of the cases surviving up to 12 months post injury. Between one and two TUNEL+ cells/unit area were also seen in grey matter, of which most appeared as neurones. About 5% of the TUNEL+ cells in white matter had the morphological features of apoptosis: the corresponding figure in grey matter was less than 1%. In many instances the TUNEL+ cells were also CD68+ and appeared by light microscopy to be macrophages. It was concluded that, as reflected by TUNEL histochemistry, long-term DNA fragmentation is present in white matter after traumatic brain injury in man. PMID- 11761719 TI - Quantification of the vacuolation (spongiform change) and prion protein deposition in 11 patients with sporadic Creutzfeldt-Jakob disease. AB - The vacuolation (spongiform change) and prion protein (PrP) deposition were quantified in the cerebral cortex, hippocampus and cerebellum of 11 patients with sporadic Creutzfeldt-Jakob disease (CJD). The density of the vacuolation, averaged over patients, was greatest in the occipital cortex and cerebellum and least in the dentate gyrus. The degree of PrP deposition was similar in the different cortical areas and in the cerebellum but significantly lower in the hippocampus and absent in the dentate gyrus. There were no significant differences in the extent of the vacuolation and PrP deposition in the upper and lower cortical laminae. Vacuolation and PrP deposition in the upper cortex were both positively correlated with corresponding levels in the lower cortex. In addition, in the parietal cortex and parahippocampal gyrus, the density of the vacuolation was positively correlated with the level of PrP deposition but no such correlations were observed in the remaining areas studied. This quantitative study suggested that: (1) the pathological changes were most severe in the occipital cortex and cerebellum, while the hippocampus was least affected, (2) the pathological changes affect the upper and lower cortical laminae, and (3) the degree of correlation between the density of the vacuolation and PrP deposition may be dependent on brain region. PMID- 11761720 TI - Plaque-like structures and arteriosclerotic changes in "diffuse neurofibrillary tangles with calcification" (DNTC). AB - "Diffuse neurofibrillary tangles with calcification" (DNTC) is a rare form of slowly progressive dementia characterized by temporal or fronto-temporal atrophy with neuronal loss and astrocytosis, neurofibrillary tangles and Fahr-type calcification, but no senile plaques in the cerebral cortex. In patients with DNTC, we detected a novel histopathological abnormality that we termed "plaque like structures" (PLS). PLS appeared as oval, slightly eosinophilic masses of up to 100 microns in diameter. With methenamine silver stain, the PLS were argyrophilic, and thread-like structures were observed in and around them. Most PLS were observed in deep layers of the cortex and subcortical white matter, and were accompanied by small vessels. They were intimately associated with the small vessel walls and astrocytes. They were composed of two types of fibers. The first type comprised straight and loosely interwoven fibers about 25-30 nm in diameter, while the other type evoked tangles. These structures have not been found in other neurodegenerative diseases, including Alzheimer's disease. In addition, to evaluate hyaline arteriosclerosis in DNTC, we examined sclerotic changes of the medullary arteries and assessed white matter lesions in affected patients. In three of four patients with DNTC, sclerosis of the medullary arteries was significantly more extensive than in age-matched controls. In all four patients, the severity of white matter lesions was graded as moderate or severe in the temporal lobe and as mild or moderate in the frontal lobe. Arteriosclerotic changes and white matter lesions can occur without hypertension and beta amyloid deposits in DNTC. PMID- 11761722 TI - Increased chromosomal imbalances in recurrent pituitary adenomas. AB - Eight pituitary adenomas (four gonadotroph cell adenomas, three prolactin cell adenomas, one null cell adenoma) and their respective recurrences in the same patients were studied by comparative genomic hybridization. Chromosomal imbalances were found in seven of eight patients affecting two of eight primary and seven of eight recurrent tumors. Overall, pituitary adenomas showed an average of 1.6 chromosomal imbalances per primary and 3.4 per recurrent tumor (P < 0.01). Prolactin cell adenomas showed an average of 4.3 chromosomal changes per primary and 6.3 per recurrent tumor, which were significantly more common than in gonadotroph cell adenomas (0 vs 1.7 changes; P < 0.05) and the null cell adenoma (0 vs 1.0 changes; P < 0.05). The most common changes were gains of 4q (in three of eight recurrences), 5q, and 13q (in two of eight recurrences each) as well as losses of chromosome 2 (in both primary and recurring tumors of two patients), 1p, 8q, 10, and 12q (in two of eight recurrences). Minimal common regions associated with recurrent adenomas were gains of 4q31.2-34 (three recurrences), 5q14-23 and 13q21-31 and losses of 12q24.3-qter (two recurrences each). The average MIB-1 proliferation indices were 1.2% for primary and 1.9% for recurrent adenomas (P < 0.005). Our findings suggest that acquisition of certain chromosomal imbalances is related to and may underlie adenoma recurrence. PMID- 11761721 TI - Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains. AB - Cerebrovascular deposition of amyloid beta protein (A beta) is a characteristic lesion of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Besides A beta, several other proteins and proteoglycans accumulate in cerebral amyloid angiopathy (CAA). We have now analyzed the expression of the heparan sulfate proteoglycan (HSPG) subtypes agrin, perlecan, glypican-1, syndecans 1-3 and HS glycosaminoglycan (GAG) side chains in CAA in brains of patients with AD and HCHWA-D. Hereto, specific well characterized antibodies directed against the core protein of these HSPGs and against the GAG side chains were used for immunostaining. Glypican-1 was abundantly expressed in CAA both in AD and HCHWA-D brains, whereas perlecan and syndecans-1 and -3 were absent in both. Colocalization of agrin with vascular A beta was clearly observed in CAA in HCHWA-D brains, but only in a minority of the AD cases. Conversely, syndecan-2 was frequently associated with vascular A beta in AD, but did not colocalize with vascular A beta deposits in HCHWA-D. The three different syndecans, agrin, glypican-1 and HS GAG, but not perlecan, were associated with the majority of senile plaques (SPs) in all brains. Our results suggest a role for agrin in the formation of SPs and of CAA in HCHWA-D, but not in the pathogenesis of CAA in AD. Both syndecan-2 and glypican, but not perlecan, may be involved in the formation of CAA. We conclude that specific HSPG species may be involved in the pathogenesis of CAA in both AD and HCHWA-D, and that the pathogenesis of CAA and SPs may differ with regard to the involvement of HSPG species. PMID- 11761723 TI - Dementia with Lewy bodies and Alzheimer's disease. AB - To investigate similarities and differences between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), we undertook a demographic analysis of 277 patients from the Kathleen Price Bryan Brain Bank with an antemortem diagnosis of probable AD. Patients with additional, possibly confounding clinical and pathologic diagnoses such as infarcts, hematomas, neoplasms, and other neurodegenerative disorders, were excluded from the analysis. Neuropathologically, AD alone was present in 192 subjects (69%), and DLB was found in 85 subjects (31%). All of the DLB cases had neuropathologic evidence of AD sufficient to meet CERAD criteria for a diagnosis of definite AD plus nigral Lewy bodies. Gender, apolipoprotein E (APOE) genotype, brain weight, age at death, duration of disease and Braak stage were compared between the two groups. Statistical analyses were performed using Fisher's exact test for comparisons of categorical data and Student's t-test for comparison of means for continuous outcomes. The proportion of males and females was balanced in the combined AD and DLB populations. There was a highly statistically significant increased frequency of APOE 3/4 in males with DLB (P = 0.007). We found higher brain weights in males with DLB versus males with AD (P = 0.012). AD was more frequent in females and DLB was more frequent in males (P = 0.019). Our findings with respect to age at death, duration of disease and Braak stage within diagnostic groups confirm previously reported findings. These data suggest that Lewy bodies are more common in males affected with dementia, especially those with the APOE 3/4 genotype. PMID- 11761724 TI - Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat. AB - The ability of putative neuroprotective compounds to protect against white matter injury remains poorly investigated due to the lack of suitable methods for assessing white matter injury. This study was therefore designed to investigate the utility of Tau 1 (oligodendrocytes/axons), myelin basic protein (MBP; myelin) and amyloid precursor protein (APP; axons) immunohistochemistry in assessing white matter injury at various times following middle cerebral artery occlusion (MCAO) in the rat. Focal cerebral, ischaemia was induced in halothane anaesthetised rats using an intraluminal thread model. At 24 h, 1 and 2 weeks following MCAO, white matter injury was assessed using Tau 1, APP, MBP and Luxol fast blue staining and neuronal injury with cresyl fast violet (CFV). In histologically normal tissue MBP immunoreactivity was detected in myelinated fibre tracts, while Tau 1 and APP were axonally located. At 24 h following permanent MCAO, MBP, and Tau 1 staining remained relatively unchanged within the myelin and axonal compartments of the ischaemic region. In contrast, increased Tau 1 staining was apparent in oligodendrocytes within ischaemic tissue, while APP accumulated in axons surrounding the lesion. At 1 and 2 weeks following transient MCAO, Tau 1 and APP staining was markedly decreased within ischaemic tissue. Marked reduction in MBP levels within ischaemic tissue were not detected until 2 weeks following MCAO. The area of axonal injury as assessed by reduced Tau 1 or APP staining correlated with the area of neuronal damage as assessed by CFV staining. This study shows that MBP, Tau 1 and APP immunohistochemistry can be utilised to assess myelin and axonal integrity following sustained ischaemia using standard image analysis techniques. PMID- 11761725 TI - Perisomatic granules (non-plaque dystrophic dendrites) of hippocampal CA1 neurons in Alzheimer's disease and Pick's disease: a lesion distinct from granulovacuolar degeneration. AB - A number of pathological changes have been reported in relation to CA1 pyramidal cells in Alzheimer's disease (AD), among them hyperphosphorylation of tau protein followed by the formation of filamentous tau lesions, granulovacuolar degeneration (GVD), Hirano bodies and spindle-shaped dilatations of distal apical dendrites. Juxtacellular clusters of glutamate receptor (GluR)-positive granules around pyramidal cells of the CA1 sector have been recently reported under the term "non-plaque dystrophic dendrites". We independently found that CA1 pyramidal cells in AD patients are regularly surrounded by ubiquitin-positive granules measuring 1-4 microns in diameter, which we have termed perisomatic granules (PSG). Using confocal microscopy, ubiquitin- and GluR-reactive granules were found to largely coincide and to correspond to the same structure. By immunoelectron microscopy PSG were found to consist of GluR1-2-reactive enlarged synaptic boutons containing tubulo-filamentous or floccular material. PSG were found to be consistently associated with pyramidal (principal) cells but not with interneurons of the CA1 sector. Dual-labeling experiments have shown that PSG are preferentially associated with tau-immunoreactive "pretangle" neurons but not with cells containing filamentous tau inclusions or with tau-negative nerve cell bodies. The number of PSG was found to increase with the severity of AD changes with almost no PSG found in Braak stages I and II and few in stage III. Furthermore, PSG were not AD specific, as shown by their presence around CA1 pyramidal cells in Pick's disease. The reasons for GluR reactivity and ubiquitin complex formation in enlarged perisomatic boutons are unclear. Marked changes in GluR subunits have been observed in association with even moderate AD pathology in hippocampal pyramidal cells in AD and our findings suggest a pathogenic link between PSG and early tau pathology in CA1 neurons. PSG might represent residual and abnormally clustered GluR subunits in degenerating perisomatic neurites. Our work confirms and extend previous study on perisomatic "non-plaque dystrophic dendrites" in AD and establish PSG as a pathological entity distinct from GVD. In addition PSG should be acknowledged among main histological changes associated with hippocampal neurons in AD and Pick's disease. PMID- 11761726 TI - New variant or iatrogenic? A response to Streichenberger et al. [Acta Neuropathol (2000) 99:704-708]. AB - Evidence is presented that the reported case may not be a new variant sensu strictiori as suggested but rather a iatrogenic case transmitted by corneal transplant or tonometry. PMID- 11761727 TI - This is really a case of new variant Creutzfeldt-Jakob. Response to C.J.G. Lang et al. concerning our article Acta Neuropathol (2000) 99:704-708. PMID- 11761728 TI - Laboring union. Loans help strained PRN (Physicians for Responsible Negotiation) keep going--but for how much longer? PMID- 11761730 TI - No more griping, OK? Arbitration panel decides UPMC Passavant must stay with health system. PMID- 11761729 TI - Fla. union aids Utah doc effort. PMID- 11761732 TI - Healthcare's new motto: all bioterrorism, all the time. PMID- 11761731 TI - Hard to kill. Medicare cost reports still a big issue. PMID- 11761733 TI - How much is enough? AHA, lawmakers debate federal funding for bioterrorism preparation. AB - The anthrax outbreak was just the beginning. Recently the nation's hospitals got their first taste of dealing with a bioterrorism attack. And as fears of different terrorist onslaughts escalate, healthcare providers struggle to answer questions they never faced before--and to anticipate new ones. PMID- 11761734 TI - On the front lines. Ad campaign seeks to buff hospitals' image as federal funding decisions are made. PMID- 11761735 TI - Queens crash an echo for hospitals. PMID- 11761736 TI - Sexual aggression against women by men acquaintances: attitudes and experiences among Spanish University students. AB - Extensive prior research has indicated that sexual assault is highly prevalent among American college students. The purpose of this study was to assess Spanish students' attitudes about forced sex and actual experiences with male-against female sexual aggression (SA) at a major university campus. A date-rape story was presented whereupon students (N = 412) indicated the extent to which they thought forced sex was acceptable or unacceptable in ten hypothetical situations (Giarusso, Johnson, Goodchilds, & Zellman, 1979). A second section examined whether a female or male Spanish student had experienced or engaged in a broad range of coercive sexual activities (Koss & Oros, 1982). A third section elicited help-seeking behavior in those cases where a female student had experienced unwanted sexual activity (Ogletree, 1993). It was hypothesized that students would differ in their acceptance of forced sex as a function of sex, branch and year of study, and actual experience with SA. Results showed that acceptance of forced sex was significantly related to sex, year of study and experience with SA. Results also revealed that 17.5% of all male students (n = 189) accepted forced sex and 33.2% of all female students (n = 223) had experienced some form of unwanted sexual activity; 7.7% of the women had experienced attempted or completed rape. Only 39% of those women victimized sought any form of help. The implications of these findings for rape-prevention programs are discussed. PMID- 11761737 TI - Evaluation of the amount of therapist contact in a smoking cessation program. AB - This research tested a multicomponent self-help manual that contained nicotine fading and some behavioral techniques. It also evaluated the incremental effects of using higher amounts of therapist contact on quitting rates. 114 smokers were randomly assigned to one of four treatment groups: (1) A 10-session multicomponent program (n = 25); (2) a 5-session multicomponent program (n = 31); (3) a 5-session multicomponent plus a self-help manual program (n = 25); and (4) a self-help-manual-only program (n = 33). A control group (n = 48) did not receive any treatment. The distinctive characteristic of the treatments was the different amount of therapist contact. Common components of the programs were a refundable deposit, self-monitoring, information on smoking, stimulus control, CO feedback, nicotine fading, and strategies to avoid withdrawal symptoms. End-of treatment quit rates ranged from 36% (self-help manual) to 68% (10-session multicomponent program). At 12-month follow-up there were significant differences between groups, and the most effective group was the 5-session plus manual group, with an abstinence rate of 48%. PMID- 11761738 TI - Machiavellianism: dimensionality of the Mach IV and its relation to self monitoring in a Spanish sample. AB - The aim of this study was to assess the measurement model of a Spanish version of the Mach IV Scale (Christie, 1970b), used to measure Machiavellianism, and its relation with the Self-Monitoring Scale (Snyder & Gangestad, 1986). 346 undergraduate students (70 males and 276 females) filled in both scales. The results of confirmatory factor analyses showed a four-factor structure to be the most adequate model for the Mach IV, with the following factors: Positive Interpersonal Tactics, Negative Tactics, Positive View of Human Nature, and Cynical View of Human Nature. These results are not in accordance with the original factor structure but are consistent with other authors' findings. A structural model between Machiavellianism and self-monitoring was tested, showing statistically significant paths between interpersonal tactics and one self monitoring subscale. PMID- 11761739 TI - Metalinguistic awareness and reading acquisition in the Spanish language. AB - This research was designed to establish the importance of phonological awareness and print awareness in learning to read Spanish. A sample of 136 preliterate Spanish children (70 boys and 66 girls) whose ages ranged from 5.1 to 6.6 years (average age 5.6 years) participated in the study. The results, using path analysis, from this longitudinal study support the existence of a relationship between phonological awareness and reading. Moreover, the findings of this study reveal the importance of syllabic awareness, at least in Spanish, in the development of other levels of phonological awareness and in its early relation with reading. The results also confirm the existence of a relationship between print awareness and reading comprehension. PMID- 11761740 TI - The role of anxiety and adaptation to illness in the intensity of postchemotherapy nausea in cancer patients. AB - The aim of this work was to assess whether cancer patients presenting high anxiety levels or poor adaptation to cancer experience higher levels of postchemotherapy nausea, regardless of the emetogenicity of the chemotherapy schedule. Sixty-three patients were interviewed before receiving their chemotherapy schedule and some psychological variables were assessed. Nausea intensity was also assessed after treatment. The results showed that patients with relatively higher levels of nausea reported higher levels of anxiety prior to chemotherapy and lower levels of adaptation to cancer. Thus, evidence for a modulating effect of psychological factors in postchemotherapy emesis is suggested. PMID- 11761741 TI - The development and construct validation of a Spanish version of an Academic Self Concept scale for middle school Hispanic students from families of low socioeconomic levels. AB - For a sample of 305 6th, 7th and 8th grade students, of whom 95% was from economically disadvantaged Hispanic families and for whom English was their second language, evidence was sought regarding the reliability and construct validity of scores on a Spanish version of an academic self-concept measure entitled Dimensions of Self-Concept (DOSC), comprising five subscales bearing the same names as those of the five hypothesized constructs that they were intended to operationalize: Level of Aspiration, Anxiety, Academic Interest and Satisfaction, Leadership and Initiative, and Identification versus Alienation. Reliability estimates varying between .72 and .80 were judged to be reasonably satisfactory. Results from oblique factor analysis lent empirical support for the hypothesized constructs of Anxiety, Leadership and Initiative, and Identification versus Alienation. Scores associated with the subscales of Level of Aspiration and Academic Interest and Satisfaction generated a factor interpreted as a fusion of the two constructs of Level of Aspiration and Academic Interest and Satisfaction. PMID- 11761742 TI - The role of subvocalization in rehearsal and maintenance of rhythmic patterns. AB - This experiment analyzed the influence of subvocal activity in retention of rhythmical auditory patterns. Retention of sixteen percussion sequences was studied. Each sequence (a 4-s "door-knocking" pattern) was followed by one of the following six retention conditions: silence, unattended music (blocking the inner ear, i.e., Gregorian chanting), unattended music (blocking the inner ear, i.e., rock-and-roll), articulatory suppression (blocking the inner voice), tracing circles on the table with index finger (spatial task), and tapping (motor control). After silence, unattended music (chanting), or the spatial task, participants successfully reproduced most patterns. Errors increased with unattended music (rock-and-roll), but significant disruptions only occurred with tapping and articulatory suppression. Whereas the latter case supports the role of an articulatory loop in retention, the production of successive taps or syllables in both interference conditions probably relies on a general rhythm module, which disrupted retention of the patterns. PMID- 11761743 TI - Scores and principal components: the relationship between components due to subjects and to variables. AB - The main purpose of this article is: given a score matrix called S, find out the joint proportional contribution of factors due to persons (conditions, situations, and so forth) and factors due to variables, for any sij observed score, where i identifies persons, and j, variables. This approach makes it possible a) to show that the same score in a given variable may have a different quantitative interpretation in terms of persons or conditions, and b) to find out how subjects differ in the way in which they relate variables. PMID- 11761745 TI - Audit forms help streamline review of guideline compliance. PMID- 11761744 TI - Psychophysiological studies of unattended information processing. AB - The article describes the general methods and some of the results obtained in the Psychophysiology Laboratory of the University of La Coruna. The paper covers our research on the Simon effect and accessory effect, although it is not a review of the literature. The research strategy we followed is built around the use of lateralized motor potentials recorded from scalp. These measures allow observing the way responses are selected and when they are selected, providing an invaluable tool to study response interference and to split reaction time into two halves. The research on the Simon effect concludes that interference during response selection is critical in the Simon effect but it is dubious whether this process should be considered as automatic and stimulus-driven, as is widely accepted. The experiments with the accessory effect indicate that facilitation is produced before response selection is over, which ends a long controversy about the locus of the accessory effect. PMID- 11761746 TI - Re-evaluating what to measure when gauging physician performance. AB - In the rush to generate data on virtually every component of physician practice, an observer resurrects some of the basic, often-forgotten tenets of sound data driven management. PMID- 11761747 TI - Gradual approach key to successful transition to electronic records. AB - Implementing an electronic document imaging system hasn't exactly been pain-free, according to health information managers at the DeKalb Regional Healthcare System in Atlanta. But DeKalb's nearly four-year project has gone well thanks to a gradual phase-in of the system. PMID- 11761748 TI - Most physicians happy with EMR installation, says new MGMA study. PMID- 11761749 TI - Few insurers HIPAA-compliant as regulatory deadline looms. AB - For health care providers, that means delays in linking payers and providers with uniform EDI formats designed to reduce errors and ease administrative burdens. In the short run, paper records may remain cheaper and easier. PMID- 11761750 TI - Web-based second opinion service expanding quickly. AB - Specialists at high-profile, prestigious health care institutions always have promoted their services among their colleagues. Now, as part of an expansion of its telemedicine services, a group comprised of Boston's medical elite is taking its message directly to health care consumers. PMID- 11761751 TI - How patients and doctors benefit from being 'wired'. AB - Physicians are finding new and better ways to communicate--electronically--with their patients, drastically reducing the paper chase normally found in a busy office. PMID- 11761752 TI - [The results of forearm fractures by percutaneous stabilization in children]. AB - Between 1997 and 1999, 332 children (251 boys and 81 girls), aged 1 to 16, with fractures of the forearm bones were treated at the Department of Pediatric Surgery and Oncology in Lodz. In 38 patients (11.4%) percutaneous intramedullary Kirschner wiring of displaced fragments was performed. Proper reduction and good union of the fractured bones was achieved in all cases. Early evaluation performed at 6 months to 2 years after surgery revealed full joint mobility, preserved bone axis and no bone-length differences in comparison with the healthy forearm. Limitation of carpal joint mobility found in 4 cases (10.5%) was treated with prolonged (3 to 6 months) therapeutic rehabilitation. No patient in the analyzed series showed any symptoms of ostitis. The obtained results indicate that percutaneous intramedullary Kirschner wiring is a simple and effective way of treating chosen cases of forearm fractures in children. PMID- 11761753 TI - [The comparison of the results of treatment of displaced supracondylar humeral fractures by skeletal traction and percutaneous K-wire fixation in children]. AB - The aim of the study was to compare of the results of treatment of displaced supracondylar humeral fractures by skeletal traction and percutaneous K-wire fixation in children. We assessed retrospectively the type and result of treatment of 23 children. We obtained very good results in all cases treated by closed reposition secured by percutaneous K-wire fixation. In the group treated by skeletal traction, in 5 cases reposition was inadequate with subsequent limitation of range of motion in the elbow joint. According to our results closed reposition and percutaneous fixation should be the method of choice in displaced supracondylar humeral fractures in children. PMID- 11761754 TI - [Treatment of scaphoid fractures and other intra-articular fractures with the Herbert screw: a preliminary report]. AB - Treatment of scaphoid fractures and other intraarticular fractures with the Herbert screw is presented. It was used in 23 patients--17 with scaphoid fractures, 5 with radial head fractures and 1 with a Bennett fracture. The surgical technique is described. Stable fixation and early post-operative rehabilitation are the most important advantages of this technique. PMID- 11761755 TI - [Long-term results of surgical treatment of lumbar disk herniation in adults]. AB - The authors present long-term results (10.2 years post-op) of surgical treatment of lumbar disc herniation in 1003 patients operated at the Department of Neurosurgery by the University of Medical Sciences in Bialystok. The operated group comprised 33.1% women (mean age--55.6 years) and 68.7% men (mean age 57.3 years). Ten years post-op 15.9% women and 5.8% men kept the recommended diet, 14% women and 7.0% men continued muscle strengthening exercise. Ten years post-op excellent and good results were noted in respectively 42.4% and 46.5% women and 45.4% and 46.6% men. PMID- 11761756 TI - [An epidemiological analysis of bilateral slipped capital femoral epiphysis in children]. AB - The aim of the study was to analyze the natural history of the "healthy" hip joints in patients with primary unilateral slipped capital femoral epiphysis (s.c.f.e.). The material consisted of 128 patients operated because of s.c.f.e. in the Institute of Orthopaedics and Rehabilitation at the University of Medical Sciences of Poznan in 1968-1991. There were 84 boys (66%) and 44 girls (34%) at mean age of 12.8 years. The retrospective analysis showed that the percentage of bilateral s.c.f.e. diagnosed primary at the onset of the disease increased significantly in the long-term follow-up. There were 13 cases (10%) of primary bilateral s.c.f.e., 16 cases (13%) with symptomatic, secondary contralateral s.c.f.e. and 55 cases with asymptomatic, "silent" contralateral s.c.f.e. Only 44 cases (34%) remained unilateral in long term follow-up. The percentage of bilateral s.c.f.e. increased from 10% at the primary admission to 66% at the long term follow-up. The secondary contralateral slip remaine often asymptomatic ("silent") making the diagnosis more difficult. Contralateral, asymptomatic slip developed more often in boys than in girls. PMID- 11761757 TI - [Results of surgical correction of congenital talipes equinovarus]. AB - Different surgical procedures in the treatment of clubfoot were analyzed, especially in correlation to over-correction and inadequate correction. Indications for surgery, surgical errors and their influence on outcome were assessed. 82 children (28 females and 54 males) with 130 congenital equinovarus underwent surgery between 1988 and 1994. Age at the time of operation ranged from 6 to 13 months (average: 9 months). Posterior release (i.e. partial subtalar release) was conducted in 68 cases of clubfeet and complete subtalar release in 62 cases. During follow-up 44 children with 64 clubfeet were reviewed. Magone's criteria were used to assess final results. 15 (23%) feet showed very good results, 26 (41%)--good results, 14 (22%)--satisfactory and 9 (14%)--poor or no correction. PMID- 11761758 TI - [Morphometric changes in tibial tunnel after anterior cruciate ligament reconstruction by autogenous bone-patella tendon-bone graft]. AB - The author evaluated morphometric changes in the tibial tunnel of 24 patients, aged 18-46 years, after anterior cruciate ligament reconstruction by bone patellar tendon-bone autograft. The evaluation comprised the width and shape of the tunnel, the age of the patient and clinical outcome within 6 to 16 months post surgery. Morphometric analysis was based on radiograms done in antero posterior and lateral view. Clinical evaluation was based on the International Knee Documentation Committee (IKDC). The shape of the bone tunnel was evaluated according to Peyrache et al. Statistical analysis was performed by using Wilcoxon paired ranked test, Mann-Whitney test and t-Student test. The results show that the width of the tibial tunnel after anterior cruciate ligament reconstruction with autogenic bone-patellar tendon-bone graft increased in a statistically significant way, but it didn't affect the functional result of the operation. Change dynamics is greatest during the first 6 months post surgery, and the range of changes may be age-dependent. PMID- 11761759 TI - [Antero-lateral impingement syndrome and evaluation of chronic post-traumatic instability in the talo-crural joint]. AB - The aim of this paper was to asses whether the antero-lateral impingement syndrome is a sequel of ligamentous-capsular element failure in the talo-crural joint. The authors evaluated stability of the talocrural joint on a stand by one of the authors (E. G.). Using Zwipp's method and the authors own method the kind and degree of instability were assessed. Radiological features of antero-lateral instability were found in 17 patients (4.6%)--7 female (1.9%) and 10 male patients (2.7%) aged from 25 to 54 years. 4 grade II antero-lateral instabilities 2 grade III lateral instabilities and 1 grade V instability concomitant to antero lateral impingement were found in the female patients. Whereas among the male patients 6 grade II antero-lateral instabilities and 4 grade III instabilities were found. PMID- 11761760 TI - [Limb-sparing surgical treatment in osteosarcoma]. AB - From 1998 we performed limb-sparing surgery in 6 patients with osteosarcoma. No evidence of disease or local recurrence was noted in any of the patients after a mean follow-up period of 13 months. Age at the time of operation ranged from 8 to 14 years. Wide resection margins were achieved in all patients. The results of functional evaluation according to Enneking were excellent in 5 cases and poor in one. Bony defects created by limb-sparing procedures may be reconstructed by many methods. In growing children, limb-sparing surgery needs special consideration to avoid later limb-length discrepancy and expandable prostheses have been used to anticipate this problem. PMID- 11761761 TI - [Construction principles, strength investigation and early clinical results of the Integracja osteosynthesis system: a preliminary report]. AB - The aim of this paper was to present the construction principles and strength investigation of the Integracja osteosynthesis system. Preliminary results of fracture treatment in 6 patients with hip and knee prosthesis are presented. Inc all cases bony union was obtained. Integracja can be successfully used in femur fractures near the tip of the prosthesis shaft. PMID- 11761762 TI - [50 years of the Lodz Branch of the Polish Orthopedics and Traumatology Society]. AB - The Lodz Branch of the Polish Orthopedics and Traumatology Society (PTO i Tr.) was founded an march 10, 1951. The first Board was selected at the plenary PTO i Tr. meeting on May 7, 1951. The aim of the first Board was to make up for the inadequacies of orthopedic and trauma care in our region and assure orthopedic it's due place in the medical sciences. It also encouraged it's members to take up scientific and social work. In the past years the number of Branch members grew from 18 to 169, proportionately to the number of new orthopedic and trauma care facilities in Lodz and it's surroundings. The members of the Branch participated in local scientific meetings a domestic PTO i Tr. congresses as well in congresses abroad. They delivered on the local meetings near 1401 research reports, which level were high. 81 members received Ph. D. and 9 of them achieve the degree of D. M. Sc. The average frequency at the scientific local meetings was 33%. From 1951 to 2000 members of Lodz Branch presented 192 papers in 23 domestic congresses of PTO i Tr. and published 325 papers as well 15 communications in organ of PTO i Tr. Lodz Branch organised three domestic meetings so called Orthopaedic Days in 1951 and 1960 as well three congresses in 1966, 1984 and 1998. Its members were also included in General Board of PTO i Tr. PMID- 11761763 TI - [Lengthening of the IV metatarsal in the treatment of the shortened toe of the foot]. AB - The author presents the results of surgical treatment of congenital shortening of the IV metatarsal in 3 girls. In 2 cases the defect was bilateral. A total of 5 feet were operated on the age of the patients at time of operation ranged from 10 years and 1 months to 16 years and 11 months. A one-stage procedure with the use of a Pumed mini-distraction device was performed. The fissure between the bone fragments was augmented with a bone graft from the fibula. It was harvested in such a way as to maintain internal cortical integrity. K-wire fixation of the bony fragments was applied for 7 weeks. Immobilization by means of a plaster cast was applied for 6 to 8 weeks. Follow-up ranged from 7 months to 3 years. In all cases an improvement of the finger shape and it's lengthening was noted, although in 2 cases lengthening wasn't complete. In one case it resulted from an axial deformity of the IV metatarsal, a sequel of early (5 weeks) removal of the K wire. PMID- 11761764 TI - [Giant intradural disk herniation]. AB - The authors present a rare case of the total intradural sequester from a prolapsed lumbar disc at the L4 level. This kind of hernations comprise 0.3% of all disc hernations. Surgical treatment resulted in a good outcome. PMID- 11761765 TI - Prescriptions for bankruptcy. PMID- 11761766 TI - Wandering. Repaving the way you think. PMID- 11761767 TI - Too many and too few: population dilemmas of the 21st century. PMID- 11761768 TI - Breaking the cycles of malnutrition: are pregnancy nutrition interventions effective? PMID- 11761769 TI - One and a half centuries of demographic transition in Nepal. AB - This paper examines the past and prospective demographic transition in Nepal. Sparse data from the pre-1961 censuses suggest that mortality decline began during 1930s and allow rough estimates of fertility and mortality levels prior to 1961. Fertility decline began sometime between 1961 and early 1980s, with the total fertility rate declining from about 6 to 5 children per woman by early 1990s. The four scenarios of future fertility decline and population growth presented in the paper help draw several conclusions. A continuation of the recent slow pace of fertility decline would result in a total population of slightly over 100 million by the end of the next century (Scenario I). More rapid decline, similar to the median experience of Asian countries, would reduce this growth to below 60 million (Scenario III). Still more rapid decline, close to the limit of what has been observed in countries that have experienced the most rapid declines, could reduce the growth to 40 million (Scenario IV). It is possible, if not at present particularly plausible, that very rapid decline might be achieved by a combination of smaller family sizes and rising age of childbearing. An approach to reaching zero population growth rapidly--and anything less than a doubling of current population--may be ruled out with a high degree of certainty (Scenario II and IV). A doubling of population to 40 million is the least possible growth that can be expected. At the current rate of fertility decline, population will increase to 100 million during this century. If a smaller population in this range is considered to be in the national interest, it is as important to work for more rapid fertility decline as it is to work for accommodation of a much larger population. PMID- 11761770 TI - Effects of vitamin A supplementation during pregnancy and early lactation on body weight of South African HIV-infected women. AB - Effects of vitamin A supplementation during pregnancy and early lactation on maternal weight among HIV-1-seropositive South African women were examined. Three hundred twelve HIV-seropositive pregnant women between 28 and 32 weeks gestation were studied as part of a randomized, double-blind, placebo-controlled trial at the King Edward VIII Hospital in Durban, South Africa. Patients were randomized to receive placebo or 5,000 IU of retinyl palmitate and 30 mg of beta-carotene daily during pregnancy. At delivery, patients received placebo or 200,000 IU of retinyl palmitate. The main outcome measures were prenatal and postnatal maternal weight and weight loss at three months after delivery as measured in body mass index (BMI). Supplementation of vitamin A was not associated with improvements in prepartum weight gain but was significantly associated with improved weight retention three to six months after delivery (p = 0.02). The benefit of vitamin A supplementation appeared to be confined to subgroups with baseline CD4+ count < 200 cells/microL and serum retinol 0-20 micrograms/dL. Similar trends were observed in maintenance of postpartum BMI. However, no statistically significant associations were observed. Although there was no benefit of vitamin A supplementation on prepartum weight gain, a benefit on maintenance of postnatal weight was observed. The benefit was highest among those who were vitamin A deficient or whose CD4+ count was < 200 cells/microL presupplementation. In populations for whom antiretroviral therapy is not readily available or accessible, the finding that vitamin A may improve postpartum weight lends some hope to a relatively inexpensive treatment which could be used for helping ameliorate some weight loss which is common during HIV infection. PMID- 11761771 TI - Survival of Shigella dysenteriae type 1 on fomites. AB - Studies have shown that various objects, such as utensils, toys, and clothes, can serve as vehicles for transmission of Shigella spp. Shigellae can become viable but non-culturable (VBNC) when exposed to various environmental conditions as shown in earlier studies. The present study was carried out to detect VBNC Shigella dysenteriae type 1 on various fomites by direct viable counting, polymerase chain reaction (PCR), and fluorescent antibody methods. S. dysenteriae type 1 was inoculated onto cloth, wood, plastic, aluminum, and glass objects. Results showed that 1.5-4.0 hours after inoculation, S. dysenteriae type 1 became non-culturable, and after five days, non-culturable but viable S. dysenteriae type 1 could be detected by both PCR and fluorescent antibody techniques. Fomites can be considered an important potential route of transmission of VBNC S. dysenteriae type 1 and a significant factor in the epidemiology of shigellosis. PMID- 11761773 TI - Emergence of multidrug-resistant Salmonella Gloucester and Salmonella typhimurium in Bangladesh. AB - Infections due to non-typhoid Salmonella, resistant to antibiotics, have recently emerged as an important health problem worldwide. Antibiotic resistance was studied by the disc-diffusion method among 3,876 (2.78%) non-typhoid Salmonella isolates cultured from 139,279 faecal samples in a diarrhoea treatment centre in Dhaka, Bangladesh, during 1989-1996. Of 499 salmonellae isolated in 1989, serogroup C (1.12%) was the most common, followed by Salmonella Typhi (0.72%) and serogroup B (0.71%). Isolation rate of serogroup B increased significantly to 2.18% (p < 0.01) in 1992 compared to 0.56% in 1991, 2.86% in 1995, and 2.48% in 1996. Serotyping of 194 serogroup B isolates revealed Salmonella Typhimurium (52%) and Salmonella Gloucester (45%) as predominant serotypes. Resistance to ampicillin (A), chloramphenicol (C), and trimethoprim-sulphamethoxazole (Sxt) (R type-ACSxt) increased to 89-100% during 1992-1996 from 20-28% during 1989-1991 (p < 0.01) among S. Typhimurium and S. Gloucester isolates. In 1993, 8-10% of the strains of both the serotypes, resistant to ampicillin, chloramphenicol, and trimethoprim-sulphamethoxazole, acquired resistance to ceftriaxone (Cr) (R type ACSxtCr), which increased to 85-92% in 1996 (p < 0.01). All were susceptible to ciprofloxacin. A 157-kb conjugative plasmid transferred R type-ACSxt from both the serotypes to Escherichia coli K-12. The findings of the study suggest the emergence of multidrug-resistant S. Gloucester and S. Typhimurium for the first time as a significant health problem in Bangladesh, and surveillance is essential to monitor the resistant non-typhoid Salmonella and identify its sources and modes of transmission. PMID- 11761772 TI - Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance. AB - Antimicrobial susceptibility of Shigella spp. and Escherichia coli, isolated from diarrhoeal patients in Lagos, was studied from March 1999 to February 2000. Four hundred fifty-nine isolates were identified as shigellae (62) and E. coli (397). Shigella flexneri, S. dysenteriae, S. boydii, and S. sonnei accounted, respectively, for 51.6%, 17.7%, 17.7%, and 13% of the total number of shigellae isolated. Eleven cases of shigellosis occurred in the age group of 0-9 years, 22 cases in the age group of 10-19 years, and 29 cases in the age group of > or = 20 years. Of the 397 E. coli isolates, 11 were enteropathogenic E. coli (EPEC), and 7 of these strains were isolated with shigellae from stools of patients aged 0-9 year(s) (71.4%) and 10-19 years (28.6%). Over 70% of the Shigella isolates were resistant to two or more drugs, including ampicillin and tetracycline. Twenty-one distinct multidrug resistance patterns were observed in these isolates. During 1990-2000, resistance to ampicillin increased from 70% to 90%, co-trimoxazole from 77% to 85%, chloramphenicol from 71% to 77%, streptomycin from 71% to 79%, and nalidixic acid from 0% to 11.3%. Resistance to tetracycline decreased from 89% to 79% but with MIC50 and MIC90 values outside the susceptible range. While resistance to ciprofloxacin and ofloxacin remained nil with MIC50 and MIC90 values of 0.008 and 0.0016 microgram/mL respectively. The results of this study revealed the endemicity of shigellosis with S. flexneri as the predominant serogroup in Lagos. Children and young adults were at a higher risk of severe shigellosis. The results also suggest that ampicillin, tetracycline, co trimoxazole, and streptomycin should not be used as the first-line drugs in the treatment of shigellosis. Nalidixic acid should still be selectively used for treatment, while ciprofloxacin and ofloxacin can be ideal alternatives. PMID- 11761774 TI - Atypical rotavirus identified from young children with diarrhoea in South Africa. AB - The study was undertaken for antigenic characterization of rotavirus strains isolated from South African children. During July 1996-July 1997, an epidemiological surveillance of rotavirus-associated gastroenteritis was carried out in Pretoria and Gauteng provinces. In total, 1,229 diarrhoeal faecal samples were collected from a pathology laboratory. Of 389 (32%) rotavirus strains detected, most (97%) were group A rotaviruses by serological assay. However, 12 rotavirus strains identified did not apparently carry the common group A-specific antigen as determined by both commercial and monoclonal antibody-based ELISAs. Electrophoretic analysis of the viral RNA genome revealed that these strains shared a common electropherotype and that this resembled the group A rotavirus constellation of RNA segments. Furthermore, the conserved terminal sequences of the group A VP6 and VP7 genes could not be targeted by standard reverse transcriptase-polymerase chain reaction with a routine set of primers to the VP6 or VP7 genes. These strains present an interesting phenotypic variation of the recognized rotaviruses and warrant further characterization. PMID- 11761775 TI - Coeliac disease in Indian children: assessment of clinical, nutritional and pathologic characteristics. AB - Coeliac disease is an important cause of chronic diarrhoea, failure to thrive, and anaemia in children. Little information on the disease is available in India. This study was undertaken to determine the prevalence, clinical, anthropometric and histological profiles of coeliac disease in patients attending a tertiary referral centre in India. Coeliac disease was diagnosed in 42 (16.6%) of 246 children with chronic diarrhoea, failure to thrive, and anaemia. The mean ages at onset of symptoms and at diagnosis were 2.4 (range 0.5-10) years and 8.3 (range 3 14) years respectively, and a mean period of delay in diagnosis was 5.9 (range 1 13.5) years. Of the 42 cases, history of failure to thrive was observed in 38 (90%), chronic diarrhoea in 37 (88%), and anaemia in 6 cases. Short stature, under-nutrition, anaemia, oedema of feet, rickets, clubbing of fingers, features of vitamin A deficiency, and B-vitamin deficiency were found in 42, 26, 38, 9, 8, 6, 3, and 2 cases respectively. Onset of symptoms, such as, chronic diarrhoea and failure to thrive, was earlier in children with subtotal villous atrophy than in those with partial villous atrophy (mean +/- SD; 2.00 +/- 1.46 years vs 3.30 +/- 2.72 years; p < 0.05). Results of the study suggest that coeliac disease is not uncommon in Indian children. Coeliac disease should be considered in the differential diagnosis, particularly in children without any symptoms of diarrhoea. PMID- 11761776 TI - Family-planning services in a low-performing rural area of Bangladesh: insights from field observations. AB - This paper mainly reports the results of an observational study carried out during 1994-1995 in five rural unions of Bangladesh to identify the barriers to adoption of family-planning methods. At the time of the survey, one-fifth of 1,889 mothers with a living child, aged less than five years, were practising modern family-planning methods. Of the methods used, oral pill was the most common (50%), followed by injectables (20%), female sterilization (13%), IUD (11%), and condom (4%). Various factors that were responsible for the low performance of the family-planning programme included: inadequacy of motivational work by the field workers, poor counselling on the management of contraceptive related side-effects, inadequate response to the needs of clients, irregular field visits, and poor supervision and monitoring. The efficiency of the programme needs to be improved to meet the demand for family-planning methods in Chakaria, Bangladesh. PMID- 11761777 TI - A child with pyopericardium. PMID- 11761778 TI - Maternal nutrition and perinatal survival. AB - This review addresses the relationship between maternal nutrition and the survival of the foetus and infant. This survey was undertaken because wide-scale programmes on maternal feeding are in process, based, not on a critical synthesis of currently-available empirical research, but on a series of nested and, at times, weakly supported, assumptions. It is concluded that: (i) maternal weight and weight gain are remarkably resistant to either dietary advice or supplementation; (ii) nutritionally-induced increased birth-weight does not universally increase the chance of survival of the offspring, since pre-pregnancy weight, at least in affluent, industrialized societies-while associated with increased birth-weight-is also associated with higher perinatal mortality; (iii) while dietary supplements during pregnancy do have a modest effect on birth weight, in contrast to a large effect in famine or near-famine conditions, this is not mediated by maternal energy deposition; and (iv) declining peripheral fat stores in late pregnancy are associated with accelerated foetal growth, and improved nutrition can lead to lower fat stores. Rather, the component of maternal weight gain associated with accelerated foetal growth is water, and, presumably, plasma volume. In the few studies, large and thorough enough to adequately address the issues, maternal feeding--both in famine and non-famine conditions--has led to lower perinatal, primarily foetal, mortality; the mechanisms are not likely to have been due only to the acceleration of foetal growth. It is concluded that there is currently an inadequate base of secure knowledge to foster improvement in the health and nutrition of poor mothers and children. The public and policy-makers alike must be informed that greater knowledge relating maternal nutrition to perinatal outcome is urgently needed to create sound health advice and to mount effective programmes. PMID- 11761779 TI - [Concealed and simulated trauma fatalities(II)]. AB - A careful investigation of fatal accidents is required due to the relevant financial consequences for the insured as well as for the insurance company. An evaluation of post-mortem cases handled by our institute from 1988 to 1998 showed that 16% of all fatal accidents were not initially classified as such; it was only possible to determine the cause by post-mortem and criminal investigation. The frequency of a relevant alcoholization varied with different types of accidents. Furthermore, of all fatal accidents, 3% were revealed to be deceptive. Those 42 cases in total, presenting themselves as fatal accidents at first glance, were later determined either to be natural deaths (n = 27), homicide (n = 11) or suicide (n = 4). In addition to this, autopsies showed 83 cases of death to be sequelae to accidents. Particularly in cases of a victim plunging out of the window or into water, it can be difficult to make the distinction between natural death--e.g. as a reason for falling--and suicide or homicide. Further difficulties can result from interpretations of the findings in cases of putrefaction, mauling by animals, defects caused by burning or severely deformed corpses. In these cases, the importance of patho-morphological findings from the autopsy must be emphasized. Indirect sequelae of accidents may be pulmonary embolism or pneumonia. The cause of death has to be classified as accidental if the chain of events is of traumatic origin. Mistakes can be avoided if the medical history is taken conscientiously. If no facts are available, the cause of death should be certificated as undetermined. Our evaluation only included autopsy cases from our institute. The concealed fatal accidents which were incorrectly certified as natural deaths or the cases dismissed by the police and the public prosecutor without performing an autopsy were not evaluated. PMID- 11761780 TI - [Psychological reaction in private accident insurance. Differences in legal apprehension]. AB - According to the provisions of private accident insurance, mental or psychological reactions are in contrast to basically not covered by insurance. The body is the object of insurance, not like third party insurance, which covers health. Since 1993 private accident insurance companies have been able to offer better coverage for mental or psychological reactions. But these possibilities for modifications of the AUB (terms and conditions of private accident insurance) introduced in 1993 constitute a departure from the traditional terms and conditions of the AUB. PMID- 11761781 TI - [Attention deficit syndrome (ADS)]. AB - Attention Deficit Hyperactivity Disorder (ADHD) in Germany is diagnosed more often than in the past. Its growing popularity is one reason for this. In the USA and Switzerland, where ADHD is better known, ADHD is diagnosed twice as often as in Germany. I have attempted to summarize epidemiological data and therapies. The various symptoms of the disease are described and the prognosis is shown, especially as these relate to life and PHI products. PMID- 11761782 TI - [Stroke management in Germany]. AB - Stroke is a leading cause of morbidity and mortality (rank 3) and thus a mass disease. Therefore, immediate access for everybody to stroke treatment services is indispensible. Therapeutic efficacy has been shown for lysis therapy and early rehabilitation in stroke units, respectively. The British-Scandinavian stroke unit concept focusses on immediately starting rehabilitation over 4-6 weeks by a specifically trained and motivated team. Since 1995, so-called stroke units are established in Germany adhering to a specific concept of the German Society for Neurology (DGN). Although referring to the British-Scandinavian concept in terms of efficacy the German concept differs fundamentally by focussing on monitoring as well as lysis therapy and neuroprotection in a short (3-5 days) stay. This is an intensive care unit approach for which scientific evidence is lacking. More essential are reasonable doubts that this concept can ever expand sufficiently to ensure comprehensive care. At least presently, stroke care is provided unevenly, thus contravening legislation (section 70 Social Security Act Vol. V). Acknowledging the restrictions the DGN adapted its concept, now advocating a two step model comprising intensive care stroke units plus rehabilitative stroke units. PMID- 11761783 TI - [Modern illnesses from the critical viewpoint]. AB - Psychosomatic illness as "modern diseases" are of increasing interest to the public. Environmental illnesses, for example assumed intoxication with organic solvents, multiple chemical sensitivity, sick building syndrome, chronic fatigue syndrome, fibromyalgia, the influence of amalgam or of electromagnetic waves and ozone are often causes of anxiety. There are many hypotheses about the origin of these diseases. Some scientists emphasize an organic basis; however, this is not generally accepted. Very often with good reason a psychological cause is supposed. Objective diagnostic criteria are not available, therefore these diagnoses may only be applied after sufficient exclusion of other known organic diseases. Mostly a psychological treatment is refused by the person affected, and a scientifically based somatic concept for the therapy does not exist. The medicolegal problems are important and often the reason for prolonged forensic confrontations. PMID- 11761784 TI - [20th ICLAM--International Congress of Insurance Medicine. Sydney, 29 April to 3 May]. PMID- 11761785 TI - [Patient self determination at the end of life]. PMID- 11761786 TI - Altering physician behavior to improve clinical performance. AB - Increasing public awareness of the need to improve quality in health care and to limit unexplained variations in clinical practice have promoted interest in altering physician behavior. Unfortunately, many programs for changing the practice patterns of providers have proven less effective than anticipated. Interventions have often been initiated without a clear understanding of their theoretical basis or the empiric data supporting their use. This article reviews the various interventions available for altering physician behavior and their evidence of effectiveness. PMID- 11761787 TI - Outcomes of care: the use of conceptual models to "see the forest and the trees" in planning outcomes studies. AB - Outcomes research provides many opportunities to explore how care activities, care processes, and care systems impact on individuals and health care resources. This article discusses clinical outcomes research and its connection to real-life situations. A model-building approach is presented to clarify the process of outcomes research by acknowledging multiple variables and how they interact. The process is illustrated through a hypothetical model addressing coronary artery disease. The usefulness of using conceptual modeling typing related variables together while creating a framework for increased understanding of key variables and their interaction is discussed. PMID- 11761788 TI - Disease management as a performance improvement strategy. AB - Disease management is a strategy of organizing care and services for a patient population across the continuum. It is characterized by a population database, interdisciplinary and interagency collaboration, and evidence-based clinical information. The effectiveness of a disease management program has been measured by a combination of clinical, financial, and quality of life outcomes. In early 1997, driven by a strategic planning process that established three Centers of Excellence (COE), we implemented disease management as the foundation for a new approach to performance improvement utilizing five key strategies. The five implementation strategies are outlined, in addition to a review of the key elements in outcome achievement. PMID- 11761789 TI - Decreasing process variation in the care of carotid endarterectomy patients. AB - Avoidable complications after successful carotid endarterectomy surgery typically occur in the immediate postoperative period; most of these complications are related to hemodynamic instability. At Saint Agnes Medical Center, process variation resulted from 22 anesthesiologists and 11 surgeons doing the same process 242 ways. We introduced a Post-Anesthesia Care Unit Carotid Order Set to standardize the process, drug sequence, and drug choices for postoperative carotid endarterectomy patients. Ongoing monitoring demonstrated that this reduction in process variability resulted in a lower complication rate for stroke and wound hematoma. PMID- 11761790 TI - Effects of a weaning protocol on ventilated pediatric intensive care unit (PICU) patients. AB - As part of a learning collaborative sponsored by the Center for the Evaluative Clinical Sciences (CECS) at Dartmouth College, a multidisciplinary pediatric intensive care unit (PICU) group began meeting in 1997 to evaluate potential performance improvement (PI) opportunities. A reduction in mechanical ventilation (MV) hours was the initial team focus. The multidisciplinary team developed and implemented protocols and physician order sets outlining care for MV weaning, neuromuscular blockade/therapeutic paralyzation, and enteral feedings. Since the initiation of our protocols in July 1997, we have significantly reduced the number of hours our PICU patients receive MV. PMID- 11761791 TI - Development of an information management system using a strategic planning process. AB - This article details the development of an information management system to facilitate the ability of clinicians to identify risk factors present in low birthweight deliveries and to determine geographic clusters of risk factors. These data would serve as a basis for planning clinical interventions at the community level. The strategic planning process provided a framework for successful design and implementation of the information management system. PMID- 11761792 TI - Translating research into practice using electronic medical records the PPRNet TRIP project: primary and secondary prevention of coronary heart disease and stroke. AB - This paper describes the background and methods of an Agency for Healthcare Research and Quality-funded study designed to evaluate the impact of a quality improvement model using academic detailing and electronic medical records (EMRs) on adherence with 22 clinical practice guidelines for prevention of cardiovascular disease and stroke. The study is being conducted in 23 primary care practices in 14 states that use a common EMR and pool data for research. Control practices receive copies of the clinical practice guidelines and quarterly updates of their adherence with them. Intervention practices receive similar information and participate in regular site visits and investigator meetings designed to catalyze their quality improvement efforts. The intervention began January 1, 2001 and will be completed on June 30, 2003. PMID- 11761793 TI - Quality improvement using electronic medical records: a case study of a high performing practice. AB - Electronic medical record (EMR) systems are useful tools that can help primary care practices improve clinical care; however, the successful implementation of an EMR system depends on dedicated users who optimize the system to suit their practice needs. This case study describes the strategies a solo, family physician practice has adopted to improve care as part of a national cardiovascular disease prevention study. PMID- 11761795 TI - Leveraging performance measurement and management: the quality and efficiency edge. AB - The University HealthSystem Consortium (UHC) is a mission-based, member driven alliance of academic health centers. UHC's objectives are to pool resources, create economies of scale, improve clinical and operating efficiencies, and influence the direction and delivery of health care. To assist our members in developing these strategies, UHC conducted concurrent clinical and operational cardiology benchmarking projects. The goals of the cardiology-benchmarking project were to: Identify successful organizational structures and operational processes used by members to provide cardiology service. Identify methods to maximize productivity, and manage supply and equipment costs. Share methods of measuring and reporting outcomes (report cards, databases). PMID- 11761794 TI - System supports for chronic illness care and their relationship to clinical outcomes. AB - The Chronic Care Model proposes that organizational system changes improve the quality of chronic care. This cross-sectional study explores the relationship between system supports for chronic care and clinical outcomes for two major chronic illnesses: diabetes and cardiovascular disease. Nine community-based primary care practices from the Practice Partner Research Network (PPRNet) are studied using practice group interviews and clinical data from the PPRNet database. As overall system support increases, providers' achievement of recommended care and desirable patient outcomes improves (r = .828, p = .006). Enhanced systems for provider decision support had the strongest positive correlation with clinical outcomes (r = .907, p = .001). PMID- 11761796 TI - Service line assessment and performance management through information integration: the case for cardiovascular services. AB - Understanding the performance of clinically sophisticated services has become increasingly vital to ensuring the success of a health care organization. Health care delivery systems and providers will require well-designed performance management systems, which is underscored by an operating environment of declining margins, increased capacity issues, and labor shortages in key areas. This article reviews the case for cardiovascular service line assessment and performance management, specifically as a case study example of strategic, focused, and actionable measurement and assessment of clinical and financial performance for both clinical and administrative leaders. The integration of administrative data for comprehensive and strategic assessment of clinically sophisticated services is explored in depth, along with product line definition and positioning. PMID- 11761797 TI - [Para/endocrine function of the vascular endothelium of healthy pregnant women and pregnant women with preeclampsia and their neonates]. AB - Abnormal endocrine/paracrine function of the vascular endothelium seems to be of most important in the pathogenesis of preeclampsia. The present study aimed to assess plasma concentration of ET-1 and NOx in maternal (M) and umbilical cord blood (UC) in 15 pregnant women with moderately severe preeclampsia (gestosis index 6.1 +/- 0.4), 15 pregnant women with mild preeclampsia (gestosis index 2.3 +/- 0.1) and in 31 healthy pregnant women (in 15 of them elective cesarean section was done). The control group consisted of 10 nonpregnant healthy women (NC). Moderately severe preeclampsia was characterised by a normal or even reduced plasma ET-1 level in maternal (0.7 +/- 0.1 pg/ml and cord blood (1.3 +/- 0.2 pg/ml) but markedly elevated NOx concentration (maternal blood 36.7 +/- 4.2 mumol/l), cord blood 33.5 +/- 3.5 mmol/l). In pregnant women with mild preeclampsia elevated ET-1 levels were found both in cord (3.41 +/- 0.6 pg/ml) and maternal blood (2.62 +/- 0.5 pg/ml) which were accompanied by elevated NOx concentrations (31.2 +/- 2.9 mumol/l and 32.4 +/- 2.3 mumol/l in cord and maternal blood respectively). A significant negative correlation was found between plasma ET-1 and NO levels in cord blood from severely preeclamptic women, but a positive one between cord plasma ET-1 level and gestosis index. CONCLUSION: Participation of altered ET-1 and NOx levels in maternal and cord blood from preeclamptic women as compensatory mechanisms providing adequate perfusion of the utero-placental unit is likely. PMID- 11761798 TI - [The relation between QT dispersion and incidence of ventricular premature beats in patients after myocardial infarction]. AB - The relation between increased QT dispersion and ventricular arrhythmias in patients after myocardial infarction is not definitely confirmed. The diurnal variation and long-term changes in QT dispersion can be a substantial cause of conflicting results presented in follow-up studies that tested the prognostic significance of QT dispersion. The present study was designed to determine the relation between incidence of ventricular premature beats (VPBs) and magnitude of QT dispersion measured in sinus beats before VPBs occurrence. The study group consisted of 306 postinfarction patients including 153 patients with VPBs and 153 patients without VPBs on a routine ECG. QT dispersion was calculated as the difference between the maximum and the minimum QT intervals across a 12-lead ECG. In the group of patients with VPBs the mean value of QT dispersion was greater than in the group without VPBs (81 +/- 40 ms versus 56 +/- 33 ms, p < 0.0001). The results of univariate analysis indicated that QT dispersion > 60 ms, corrected QT interval > 465 ms, QRS complex > 100 ms and RR interval < or = 800 ms were all associated with VPBs incidence. Discriminant analysis of these variables revealed that QT dispersion > 60 ms was the strongest indicator of VPBs recorded on a routine ECG (F = 47.88; p < 0.0001). Increased QT dispersion is an electrocardiographic marker of susceptibility to ventricular premature beats in patients after myocardial infarction. PMID- 11761799 TI - [Serum soluble tumor necrosis factor alpha receptor (s-TNF-alpha R) and acute phase proteins as factors of a disease activity (and also as prognostic factors?) in patients with malignant lymphomas]. AB - It was found that in neoplastic disorders levels of sTNF-alpha R and acute phase proteins are elevated and correlate with disease activity and poor prognosis. The aim of the study was to determine levels of sTNF-alpha R and acute phase proteins in patients with lymphoma at presentation and after treatment and compare with healthy individuals. Serum concentration of sTNF-alpha R was estimated by ELISA method, fibrinogen and haptoglobin by nephelometric method in 46 lymphoma patients and in 14 healthy individuals. Mean sTNF-alpha R concentration in lymphoma group was statistically significantly higher than in healthy individuals (p = 0.00057) and in patients with complete remission (CR) (p = 0.024). Mean concentration of fibrinogen and haptoglobin was significantly statistically higher at presentation of lymphoma than in CR (p = 0.0001, p = 0.0001). We found the correlation between the mean concentration of sTNF-alpha R, fibrinogen and haptoglobin at presentation of lymphoma. There was no difference in the survival time in patients with higher concentration of sTNF-alpha R. Our data indicate the important role of the elevated concentration of sTNF-alpha R, fibrinogen and haptoglobin as factors of disease activity in lymphoma patients but they do not correlate with disease's prognosis. PMID- 11761800 TI - [Dental status and efficacy of Helicobacter pylori eradication]. AB - Beside stomach Helicobacter pylori can colonize the oral cavity. One may think, therefore, that if H. pylori persists the eradication therapy in the oral cavity, it could infect the stomach again. Since in the oral cavity H. pylori occurs most frequently in a dental plaque gathering on teeth, the aim of the study was to investigate whether the natural teeth status is important for the efficacy of H. pylori eradication. The study was conducted on 45 peptic ulcer patients with natural teeth. They were eradicated with one of two regimens: 1/OAT-omeprazole (2 x 20 mg), amoxicillin (2 x 1000 mg), tinidazole (2 x 500 mg) (14-day course), 2/OAC-omeprazole (2 x 20 mg), amoxicillin (2 x 1000 mg), clarithromycin (2 x 250 mg) (7-day course). Dentistry examination was performed 4-6 weeks after the end of eradication therapy and consisted of determination of the number of teeth, caries index, dental treatment index, plaque index, and periodontal index. It was found that in successfully eradicated patients with OAT regimen, the number of teeth was higher and caries index lower than in those whose eradication therapy was unsuccessful; 24.8 +/- 5.2 vs 15.5 +/- 8.6 (p < 0.01) and 31.4% vs 46.0% (p < 0.01), respectively. The number of teeth and caries index were not associated with the efficacy of H. pylori eradication in OAC treated group. Irrespectively of the eradication regimen used, OAT or OAC, dental treatment index, plaque index, and periodontal index were not associated with the efficacy of H. pylori eradication. It is concluded that the natural teeth status may have influence on the outcome of H. pylori eradication. One should remember about this prescribing drugs for H. pylori eradication. PMID- 11761801 TI - [ST-segment shift in V1-V3 in patients with inferior wall infarction depend on angiographic localization of right artery occlusion]. AB - Two electrocardiographic types of inferior wall infarct were isolated based on angiographic localization of right coronary artery occlusion. In proximal occlusion of RCA before right ventricular branch there is no depression or more rarely elevation of ST segment in V1-V3 especially in V1 (the first morphological type). ST segment depression in V1-V3 (second morphological type) is characteristic for distal segment of RCA occlusion. PMID- 11761802 TI - [Transcatheter closure of atrial septal defects in adults with the Amplatzer atrial septal occluder]. AB - In many centres the Amplatzer Septal Occluder (ASO) (AGA Med. Corp. Minnesota, USA) has become the device of choice for secundum atrial septal defect (ASD) closure in children. Current trend towards transcatheter closure of ASD in children could be translated to adults and many patients (pts) may avoid the need of open heart surgery. Assessment the efficacy and complication of device occlusion of ASD in adults, using ASO. Between October 1997 and April 2001 transcatheter closure of ASD was attempted in 51 pts who fulfilled the inclusion criteria--significant shunt with sufficient rims of interatrial septum. Mean age of pts was 29 (16-63) y, mean ASD diameter assessed by transesophageal echocardiography (TEE) was 14.7 (7-24) mm, assessed during catheterization by balloon sizing (stretched diameter) was 20.2 (8-36) mm. There were 9 pts with multiple ASDs, 2 pts with aneurysm of interatrial septum and 2--after previous surgery (recanalization of ASD). The ASO devices were successfully implanted in all, but one pt. In one patient because of unstable position of ASO (floppy rims), device was removed and bigger one was applied during next session. In one case early embolization to abdominal aorta occurred, ASO was translocated to aortic arch with Dotter basket and removed from aorta during simultaneous surgical closure of ASD. Mean fluoroscopy time was 15 (4-50) min. The occlusion rate after 24 h was 90%, after 1 month (m) 92%, after 3 m 93.5%, after 1 year (y) 93.3% and after 2 y 93.3%. All residual shunts were trivial. There were no late complication. CONCLUSIONS: The excellent results of ASD closure with ASO in adults indicate this treatment as a method of choice in selected patients, but long term follow-up is necessary to state final judgement. PMID- 11761803 TI - [Clinical variability in two cases of systemic mastocytosis]. AB - Two cases of systemic mastocytosis with different clinical course were described. The first of them manifested with returning attacks of tachycardia with raise of blood pressure, followed by its drop and loss of consciousness. Abdominal pain and persistent diarrhea characterized the second one. The common signs in both cases were skin changes of urticaria pigmentosa, presence of Darier's symptom, very high blood levels of tryptase and prostaglandin D2 and rise in urinary LTE4 concentration. Differential diagnostic is discussed and histopathology bone marrow biopsies are presented. PMID- 11761805 TI - [The role of proteoglycans in pathogenesis and therapy of osteoarthritis]. PMID- 11761804 TI - [Recurrent Zieve's syndrome: a case report]. AB - We report a case of recurrent Zieve's syndrome, consisting of jaundice, hemolytic anemia and hyperlipoproteinemia, initiated by alcohol abuse. The crucial feature of this syndrome, which allows differentiation with common acute alcoholic hepatitis, is the presence of hemolysis. There is no specific treatment, and restraining from alcohol consumption remains the basic prophylactic measure. PMID- 11761806 TI - [Pathogenetic mechanisms of chronic renal disease progression]. PMID- 11761807 TI - [The progression of chronic nephropathies: risk factors identification and management]. PMID- 11761808 TI - [Molecular and cellular mechanisms of aging]. PMID- 11761809 TI - Laboratory information systems. PMID- 11761810 TI - [Pathogenesis of exercise induced asthma]. AB - Exercise induced asthma is an exaggerated airway response to airway dehydration and the following mediators release from the inflammatory cells. The airway narrowing is primarily caused by bronchial smooth muscle contraction, but in milder form mucus production, airway edema and cough can be observed. In this study we have described some previously and currently proposed hypotheses which may explain pathomechanism of this form of bronchial hyperreactivity. PMID- 11761811 TI - [Interleukin-2 and interleukin-6 in serum as markers of disease progression in systemic sclerosis]. AB - It is hypothesized that abnormalities of cell-mediated immunity participate in the pathogenesis of systemic sclerosis (SSc). However, the role of many cellular markers of immune activation remain still not well known, particularly as comparable with clinical status. The aim of this study was to examine the levels of some cytokines: IL-2, IL-6, TNF-alpha and to evaluate their role as parameters of disease activity and severity in systemic sclerosis. Fourty-seven patients with SSc we included in the study. Concentrations of cytokines were determined by an-enzyme-linked immunosorbent assay--ELISA. Controls were healthy age-and-sex marched volunteers. Interleukin-2 was identified in 45% of sera from patients with SSc, predominantly among patients with the rapidly progressive disease and with the diffuse SSc. The presence of IL-2 in SSc sera may also be indicative of disease activity. The frequency of positivity for IL-6 in examined SSc sera was similarly and was 50%. The prominently frequent incidence of the IL-6 in early stage of disease and in patients with severe systemic involvement indicated a potential role of this cytokine as a parameter of disease activity. TNF-alpha was not detected in the examined sera. PMID- 11761812 TI - [Changes of serum il-6 and CRP after chemotherapy in patients with ovarian carcinoma]. AB - The levels of IL-6, CRP and TPS were measured in 38 patients with ovarian carcinoma in different histological types and clinical stages. The values IL-6, CRP and TPS were determined before and after chemotherapy. Pretreatment levels of IL-6, CRP and TPS were significantly increased in carcinoma patients relatively to the control group. The frequency of increased results and absolute value of IL 6 and TPS levels showed tendency to significant increase with the stage of disease. The highest values of IL-6 were observed in patients with serous and mucous carcinoma. The levels of IL-6, CRP and TPS were decreased above cut off values in patients with remission, and did not changed in patients with progression and stabilization disease. The results suggest that IL-6 especially in the combination with CRP and TPS may be useful in the diagnosis and the evaluation of therapy of patients with ovarian carcinoma. PMID- 11761813 TI - [Liver biopsy: the mandatory test in liver diagnosis in adults]. AB - The aim of the study was clinical and morphological analysis patients with liver biopsy. In this work technique of percutaneous liver biopsy, indications, contraindications and complications were presented. Among 547 liver biopsy 56% patients was HCV infected and a 14% patient was HBV infected. Microscopic examination was performed the similar percentage the stage of inflammation and fibrosis. Among patients without viral infection (HBV and HCV) the most finding was steatosis and liver cirrhosis. Agreement of clinical diagnosis with results of microscopic investigations with reference to of inflammable changes carried out 90%, the less agreement with steatosis, cholestasis and hemosiderosis. In 30% patients after biopsy were pains in place executed of intervention and right arm for 6 hours. 0.5% of patients was sub capsular bleeding after intervention. We no observed dangerous complications after liver percutaneous biopsy. Liver biopsy is very important investigation in liver diagnosis, comparatively safety if contraindications are complains. PMID- 11761814 TI - [Cancer procoagulant activity in cases of esophageal, stomach and colorectal cancer considering progression degree and histological type of cancer]. AB - The cancer procoagulant activity has been evaluated in homogenates of esophagal, stomach and colorectal cancer tissues and in the blood serum of patients with these neoplasms's. Activity of CP was significantly higher in examined material than in control. The correlation between CP activity and progression degree as well as histological type was affirmed. The higher activity of CP in homogenates as well as in serum was observed in cases with higher degree of clinical progression and smaller activity of this enzyme corresponded with lower degree of the cancer progression. The highest activity of CP was observed in the cases of adenocarcinoma whereas the lowest in cases of squamous cell carcinoma. Higher activity of CP in homogenates of examined tissues correlated with higher activity of this enzyme in the serum. Activity of CP depended on the tissue localisation of the cancer and the highest was in the cases of stomach cancers whereas the lowest was in the cases of esophagal cancer. PMID- 11761815 TI - [Video-laryngo-stroboscopy in diagnosis of senile voice disorders]. AB - Clinical applications of videolaryngostroboscopy (VLSS) in 110 senile persons in phoniatrics was investigated. Each patient was examined laryngologically and phoniatrically. The patients were divided into two groups, according to the changes observed in the larynx as edema and vocal folds atrophy. Measurements of vibration, amplitudae, frequency glottic closure and oscillation (mucosal wave) of vocal cords yielded objective information about vibration in edema and vocal fold atrophy. This method can find application in training and therapeutic procedures in patients with senile dysphonia. PMID- 11761816 TI - [Malignant or benign thyroid nodules: a diagnostic dilemma]. AB - The aim of this study was to determine the incidence of cysts and cystoid-solid lesions in thyroid carcinomas basing on preoperative ultrasonographic examinations (USG), fine needle aspiration biopsy (FNAB) and postoperative histopathological examinations. 661 patients with different thyroid disorders were treated surgically. Carcinoma was found in 46 patients (3.9%). Papillary carcinoma was predominant (n = 34). Of the 46 patients with carcinoma, preoperative USG examination revealed cystic or cystoid-solid lesions in 18 patients (39%). FNAB of this 18 patients was positive in 5 cases, negative in 4 and suspect in 9. In 6 cases the neoplastic lesion was strictly connected with cysts (foci in the wall or in solid masses within the cyst) and in the remaining 12 patients lesions were found in the vicinity of the neoplastic focus. We conclude that malignant neoplasms of the thyroid gland are frequently (in approximately 40%) accompanied by cystic and cystoid-solid lesions, FNAB diagnostic material should be obtained even through several USG-controlled punctures and negative FNAB does not exclude thyroid carcinoma, particularly in nodular-cystoid goitre. PMID- 11761817 TI - [Sodium cromoglycate in the treatment of food hypersensitivity in children under 3 years of age]. AB - Dietary elimination is a treatment of first choice in food hypersensitivity. Such therapy is not always enough to stop the disease and introduction of pharmacological treatment is necessary. In prevention and long term treatment antiallergic drugs are recommended. The aim of the study was to assess efficacy and safety of oral sodium cromoglycate in treatment of food hypersensitivity in the youngest children. In our study we examined: the group of 25 children aged 6 months-3 years treated with oral cromolyn sodium during the period 4-20 weeks and 29 children aged 6 months-3 years treated with ketotifen. Symptoms from skin, digestive and respiratory tract, behaviour status were evaluated for drugs efficacy. Cromolyn and ketotifen effected a significant decrease in total symptoms score. The treatment was well tolerated. No serious side effects were noted. The incidents of skin rash, disquiet during the night, diarrhoea and urticaria were only 8 percent. Sodium cromoglycate is safe and effective drug in treatment of food allergy in children; specially in symptoms from gastrointestinal tract and multi-organs allergy. PMID- 11761818 TI - [The assessment of the effectiveness of the shark liver oil in recurrent aphthous stomatitis treatment: clinical and immunological studies]. AB - There is no specific and effective treatment for recurrent aphthous stomatitis (RAS), which is connected with its unexplained etiology. The purpose of this study was to determine the clinical efficiency and immunomodulation of the shark liver oil in treatment of recurrent aphthous stomatitis. Twenty-five patients with severe disease received treatment with shark liver oil during a three-month period. The frequency of occurrence of RAS decreased from 1.56 before treatment to 0.95 after treatment and the number of lesions per month was significantly reduced during the third month of treatment and two months after treatment. During two months after treatment 4 patients had no ulcers and an improvement was exhibited in all except 3 of the remaining patients. The treatment had an influence on some immunological parameters. A better response of neutrophils to OZ and PMA were seen. The B cell and T CD3/HLA DR+ cell percentage returned to normal values. A significantly increased percentage of T cells was observed as compared to the before treatment value. The level of C4 and the hemolytic activity of the complement system decreased after treatment and neared the normal values. The shark liver oil contains compounds that have a positive immunomodulation action and alleviate the course of disease. PMID- 11761819 TI - [The effect of inhaled ambroxol treatment on clinical symptoms and chosen parameters of ventilation in patients with exacerbation of chronic obstructive pulmonary disease patients]. AB - It was a randomised, double-blind, placebo controlled comparative study of the clinical symptoms and chosen parameters of ventilation of inhaled ambroxol in patients hospitalized with exacerbation of chronic obstructive pulmonary disease (COPD). Eligible patients--30 patients (13 men and 17 women) aged of mean value 70.5 +/- 6.9 years who fulfilled the clinical traits of exacerbation of chronic bronchitis entered the study. 15 patients were treated with inhaled ambroxol and 15 were treated with placebo. Moreover all patients were treated with concomitant medications typical for exacerbation of COPD (systemic steroids, intravenous infusions with euphillin, antibiotics, Berodual nebulizations and oxygen therapy). Spirometry and data related to clinical symptoms were taken at the beginning of the study and after 1 and 3 days and after the end of the treatment. At the end of the treatment period in both groups (inhaled ambroxol therapy vs. placebo) there wasn't found statistically significant difference in the number of cough and dyspnoe attacks. There was found the difference in FEV1 and FEF 50 in both groups, but improvement in patients treated with ambroxol was statistically significantly faster, that can influence the cost of treatment. Moreover there were not found important adverse events in ambroxol group. PMID- 11761820 TI - [The effect of specific immunotherapy on serum eotaxin level in patients with pollinosis: preliminary studies]. AB - Eotaxin belongs to CC chemokines with selective activity for eosinophils and basophils. Specific immunotherapy (SIT) represents the only curative approach for allergic inflammation. The aim of this study was an evaluation of the effect of SIT on serum eotaxin level in patients with seasonal allergy. 40 patients (mean age 26 +/- 8.15 with seasonal allergy to birch, 25 with seasonal allergy to grasses) and 35 persons (mean age 27 +/- 8) of the control group took part in this study. Preseasonal immunotherapy (Allergovit, Germany) was performed in conventional schedule in patients with pollinosis. Clinical assessment of symptoms in season (score) was done by all of the patients studied. ELISA test was used to measure serum eotaxin level (pg/ml, kits from R&D) before, after immunotherapy, in pollen season and after season in patients with disease. There was observed increased eotaxin concentration in patients with allergy to birch (140.6 +/- 53.7) as compared to the eotaxin level in the control group (102.1 +/- 53.7) (p < 0.05). There was observed decreased eotaxin level after immunotherapy (115.9 +/- 49.9) (p < 0.05) in patients with allergy to birch, but no with allergy to grasses. When patients with clinical improvement were taken into account, the significant difference (p < 0.05) in eotaxin concentration was showed before (126.7 +/- 52.4) and after immunotherapy (102.5 +/- 44.8). The eotaxin level in pollen season of patients with clinical improvement was significantly (p < 0.05) decreased (116.5 +/- 54.3) as compared to the eotaxin level in patients without clinical improvement (139.8 +/- 46.3). The results suggest an involvement of eotaxin in pathomechanism of SIT. The effect depends on kind of allergen evaluated. Further longitudinal controlled investigations should establish the role measuring serum eotaxin level in the clinical evaluation of SIT. PMID- 11761821 TI - [The effect of triamcinolone, montelukast and formoterol on serum levels of il-4, IgE and clinical parameters in children with asthma]. AB - Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways, contributing to allergic inflammation. The purpose of this study was to define the effect of treatment with triamcinolon, montelukast, and formoterol on serum level of IL-4 and IgE, clinical parameters (symptom score, FEV1) and bronchial hyperreactivity (BHR) in children with moderate asthma. It was 8 week, placebo controlled and randomized, double blind trial of 99 children with moderate atopic asthma allergic to dust mite. Patients were randomly allocated to receive 400 mg triamcinolon (n = 20), 5 or 10 mg (according to age) montelukast (n = 18), 24 mg formoterol (n = 19), or placebo (n = 42). 80 children completed the study. After treatment with triamcinolon, montelukast, and formoterol the level of IL-4 in blood serum in all study groups significantly decreased, and all clinical parameters improved; treatment with triamcinolon, formoterol, and montelukast had no effect on IgE level in serum. Mean IL-4 levels in serum before and after treatment with triamcinolon were 0.129 pg/ml with 95% Cl, 0.1-0.145 pg/ml and 0.086 pg/ml with 95% Cl, 0.023-0.109 pg/ml respectively (p = 0.02); with montelukast were 0.123 pg/ml with 95% Cl, 0.57-0.82 pg/ml and 0.102 pg/ml with 95% Cl, 0.62-0.82 pg/ml respectively (p < 0.001); with formoterol were 0.128 pg/ml with 95% Cl, 0.108-0.164 pg/ml and 0.113 pg/ml with 95% Cl, 0.096-0.146 pg/ml respectively (p = 0.002). No correlations have been found between changes in serum IL-4 and any other clinical parameters after treatment. This study demonstrates that one of the possible ways by which triamcinolon, montelukast, and formoterol contribute to inhibition of allergic inflammation is by decreasing IL-4 levels. PMID- 11761822 TI - [Cases of carcinoid tumor in stomach and retroperitoneal space]. AB - Authors present two cases of carcinoid localized in stomach and retroperitoneal space. Diagnosis was based on clinical examination, endoscopy, CT and histopathological evaluation. The case of gastric carcinoid was an early lesion (penetrated only mucose and submucose layer of gastric wall). In opposition, second patient had inoperable large tumor localized in retroperitoneal space with multiple metastases to the liver. PMID- 11761823 TI - [Tubulointerstitial nephritis related to immunotherapy and immunostimulation: a report of two cases]. AB - Two cases of tubulointerstitial nephritis (TIN) with renal failure related to immunotherapy (case 1) and immunostimulation (case 2) have been described. Case 1: 18 years old male patient with hay fever was admitted because of rapid increase of serum creatinine from 1.1 mg/dl to 5.5 mg/dl, fever, weight loss and anemia which developed during 6 months after second course of immunotherapy. Case 2: 12 years old boy was admitted because of fever, weight loss and rapid progression to renal failure after treatment of pharyngitis with antibiotics and immunostimulant drug. In both patients renal biopsy was performed and TIN with huge lymphocytes T infiltrates was diagnosed. After 6 months treatment with corticosteroids renal function turned back to previous levels in both patients. Pathogenesis and treatment of TIN is discussed. PMID- 11761824 TI - [Histiocytic necrotizing lymphadenitis (Kikuchi disease): a case report]. AB - Histicytic necrotizing lymphadenitis (Kikuchi disease) is a benign, self-limited disorder occurring in young adults, that is sometimes confused with malignant lymphoma. A definitive etiology has been not identified. Kikuchi's disease is characterized by collections of histiocytes and lymphocytes surrounding areas of necrosis in lymph nodes, containing fragments of karyorrhectic nuclear debris. There has been a report of a case of Kikuchi disease. We suggest that Kikuchi disease be considered as one of the differential diagnoses in young patients presenting with cervical lymphadenopathy and fever of unknown origin. PMID- 11761825 TI - [A case of cancer transformation of planocellular papilloma of the lip into squamous cell carcinoma]. AB - Authors presents the case of cancer transformation papilloma planoepithelial of lip into squamous cell carcinoma in 26-years old man. They give attention to necessity of radical remove all changes around the lips. It is especially important because of possibility of cancer transformation in every case of papilloma of lip. PMID- 11761826 TI - [Acrodermatitis chronica atrophicans in the course of old Lyme disease]. AB - Lyme borreliosis is chronic spirochetal infection with phasic course. Lyme disease can be recognised as early or late stage of disease. A case report of patient with acrodermatitis chronica atrophicans in the course of chronic (late) Lyme borreliosis is presented. As it is described, the lack of uncognition of infection of B. burgdorferi and typical signs of erythema migrans as well as a lack of proper therapy in this time may be a reason of passing into chronic phase of the disease like ACA and Lyme arthritis. PMID- 11761827 TI - [Current opinions on embryotoxic and teratogenic effects of ibuprofen]. AB - Ibuprofen is a non-selective cyclooxygenase (COX) inhibitor with analgesic, antipyretic and antiinflammatory activity. Experimental, clinical and epidemiological studies, led on a wide scale, showed high therapeutically activity and good drug tolerability, especially for low doses in adult and children older then 6 months. Those data let to positioned ibuprofen to over-the counter (OTC) drugs. However, unlike well-documented tolerability studies of the postnatal period the prenatal data are still unclear. Results of experimental studies showed ibuprofen-dependent: implantation disturbances, blocking of parturition, and contraction of ductus arteriosus what could produce persistent pulmonary hypertension. These data has been partially confirmed in human studies. Lack teratogenic effect was observed in in vivo animal studies. Gastroschisis is the only congenital ibuprofen-related malformation that was proved in big epidemiological human studies. Other congenital anomalies and disturbances, such as oligohydramnion, associated with maternal ibuprofen ingestion, and reported in available literature, have not been established in epidemiological studies. PMID- 11761828 TI - [Drug-induced heart failure]. AB - Heart failure is a clinical syndrome caused mainly by cardiovascular diseases such as coronary heart disease, hypertension and valvular disease, but several categories of drugs may potentially induce heart failure in patients without previous heart disease or precipitate revealing of heart failure symptoms in patients with preexisting left ventricle impairment. Pathophysiologically drugs that increase preload, afterload or have negative inotropic properties may be able to cause this adverse reaction. In the article the potential role in the occurrence of heart failure of cytostatics, immunomodulating drugs, nonsteroidal anti-inflammatory drugs, calcium channel blockers, beta-adrenoceptor antagonists, antiarrhythmics, anesthetics and antidepressants is reviewed. PMID- 11761829 TI - [Single non-parasitic liver cysts]. AB - Solitary non-parasitic cysts of the liver (NPHC) are rare. The incidence of NPHC on autopsy is 0.2% to 0.5% and on imaging from 2.5 to 4.6% of the population. They are more common in females than males. Congenital cysts can be solitary, multiple or involve the whole liver which is referred to as polycystic liver disease (PCLD). Post-traumatic, neoplastic and echinococceal cysts are acquired lesions. Imaging procedures (USS, CT, MRI) are essential in diagnosis of hepatic cysts. Further diagnostic procedures include cytological, bacteriological and biochemical analysis of cystic fluid. Cystography can exclude communication of the cyst with the ductal system. Serologic tests are used in hydatid disease and serum tumour markers (CEA, CA 19-9) are measured to aid in differential diagnosis of suspected neoplastic cysts. Various therapeutic methods are used in the treatment of solitary non-parasitic hepatic cysts. The simplest is percutaneous obliteration with, for example ethyl alcohol. Fenestration (deroofing) with excision of the cyst wall is increasingly more often performed laparoscopically. Conventional open deroofing is used exceptionally, mainly in complicated cases. PMID- 11761830 TI - [The Mediterranean diet: cultural factor or prevention of civilization diseases?]. AB - Cardiovascular diseases and neoplasms are still the most frequent cause of morbidity. Abnormal diet is an important risk factor of the diseases. Therefore, there is a need to apply activities leading to changes in life style and nutrition. The most important features of the Mediterranean diet and the benefits by its use are described in this article. PMID- 11761831 TI - [Dermatoglyphic morphology in some diseases]. AB - Dermatoglyphic polymorphism results from the co-operation of genetic and environmental factors during the early stages of ontogenesis. Such elements as intrauterine viral infection, radiation, alcohol, drug or certain medicaments taken by pregnant women are able to essentially disturb the formation of dermatoglyphics, if only act before the 19th week of pregnancy. Also various genetic anomalies can result in improper morphology of ridge traits. Therefore, the dermatoglyphic analysis is a valuable completion of diagnosis of some diseases (phenyloketonuria) and syndromes genetically determined (e.g. Down, Turner or Klinefelter syndromes). Regardless of the mechanism resulting in disturbed ridge traits, the new figures of dermatoglyphics are never formed, instead the altered prevalence of particular forms of ridge traits and/or the changed direction of dermatoglyphics are revealed. The improper types of dermatoglypics--in particular when found in complexes--suggest the existence of developmental instability of an organism. PMID- 11761832 TI - [Prevalence of chlamydia pneumoniae antibodies in patients with coronary heart disease]. AB - A possible role of infectious agents in the pathogenesis and progression of cardiovascular system diseases has been postulated by many scientists. The purpose of our study was to evaluate the correlation between Chlamydia pneumoniae infections and coronary heart disease. A group of 211 patients including: 120 patients with coronary heart disease (CHD) [63 patients enrolled for precutaneous coronary interventions (PTCA), 14 with proven restenosis after PTCA and 43 after coronary artery bypass grafting with recurrence of CHD symptoms], 17 patients suffering from congenital heart diseases or mitral valve stenosis with normal coronary angiograms and 74 healthy volunteers were tested. The levels of serum IgM, IgG and IgA antibodies for Chlamydia pneumoniae were measured with indirect microimmunofluorescence test (MRL Diagnostic, USA). C. pneumoniae specific IgG antibodies were detected in both, patients as well as healthy volunteers. They were seropositive with similar frequency (28.3% and 28.6% respectively). Among CHD patients, however, in PTCA/rest patients, specific C. pneumoniae antibodies have been detected more often (42.9%). Prevalence of C. pneumoniae specific antibodies correlated with patients' age, sex. There was no relation between behavioral habits (smoking) and presence C. pneumoniae antibodies. PMID- 11761833 TI - [Collective outbreaks of foodborne infections and intoxications in Poland in 1985 1999]. AB - In outbreaks of foodborne infections and intoxications in 1985-1999 in Poland among salmonellas S. Enteritidis amounted for 84.9% in 1986 and 97.8% in 1991 1992. In 1985-1999, among the total number of diseases in outbreaks most of the cases occurred after eating of the dishes made from eggs (over 50%). In 1987 1999, food prepared in private homes had the largest influence on the occurrence of the outbreaks (up to 65.4% of outbreaks). The private homes were also the most frequent places of the consumption of that food. Contamination of the ready-made dishes was found to be due to the raw materials, mainly eggs coming from private farms. In Poland and in neighboring countries Salmonella of animal's source determines the epidemiological situation of foodborne infections and intoxications. PMID- 11761834 TI - [Epidemiology of rotaviral infections in children]. AB - Problems of rotavirus infections in children were presented. The rotaviral structure, features, epidemiology and clinical course of infection were discussed. Rotaviral infection plays an important role in the hospital settings. Passed rotaviral infection leaves the immunity. The most serious clinical course of rotaviral infection concerns children 6-24 months of age. In the Third World countries rotaviral infections are one of the most frequent causes of death in infants and toddlers. It is necessary to elaborate the effective anti-rotaviral vaccine. PMID- 11761835 TI - [Chronic hepatitis C and risk for hepatitis A infection]. AB - The aim of this study was to determine the prevalence of anti-HAV antibodies and factors associated with HAV infection amongst patients with chronic hepatitis C. The prevalence of anti-HAV antibodies in hepatitis C patients was 69.2% and did not differ significantly from 63.3% observed in the group of healthy controls. In patients with chronic hepatitis C the occurrence of HAV antibodies was not associated with the duration of HCV infection, history of transfusions and surgeries. There was a tendency towards higher prevalence of anti-HAV in persons with history of numerous hospitalizations (60.8% of persons with the history of up to 5 hospitalizations were positive for anti-HAV and more than 84.6% of those with more than 5 hospitalizations). Only 38.5% of patients under 35 years had anti-HAV antibodies. In conclusion immunization against hepatitis A should be recommended for hepatitis C patients under 35 years of age, most of whom are not immune to HAV. Testing for anti-HAV prior to vaccination should be performed in individuals older than 35 because natural immunity is common. PMID- 11761836 TI - [Adherence patterns of Escherichia coli strains isolated from children with diarrhea]. AB - Among enteropathogenic E. coli strains (EPEC) there are different patterns of adherence to the culture cells in vitro assay: localized, localized-like and diffuse. The adherence pattern is dependent on the ability of E. coli strains to cause of diarrhea. The strains locally adhering possess a 60 MDa plasmid--E. coli adherence factor (EAF), and produce characteristic histopathologic intestinal lesions linked with the presence of chromosomal eae gene. The pathogenicity of diffusely adherent as well as cells detaching E. coli (CDEC) remains controversial. The aim of the study was to identify the adherence patterns of E. coli strains isolated from children with diarrhea and to compare that patterns with the serotypes and the presence of EAF and/or pO157 plasmids, fimbriae and eae, stx1, and stx2 specific sequences. Nine out of examined E. coli strains showed the localized pattern of adherence. About half (46.8%) of strains were diffusely adherent and six isolates were cells detaching E. coli (CDEC). A total of 22 (23%) examined strains showed the presence of specific for verocytotoxins sequences. The results showed that many strains recognized on the ground of agglutination with specific EPEC antisera as unpathogenic could be an etiologic agents of diarrhea which are able to produce histopathologic lesions in the intestinal epithelium. In turn, many strains classified as EPEC could be unpathogenic on the basis of diffuse pattern of adherence. PMID- 11761837 TI - [Immunoenzymatic test ELISA in serodiagnosis of chronic brucellosis]. AB - Though the acute Brucella abortus infections among cattle and humans are not observed farm and veterinary service long standing workers have been still appearing with clinical symptoms resembling chronic brucellosis. The aim of the study was to evaluate usefulness of immunoenzymatic enzyme-linked immunosorbent assay (ELISA) in serodiagnosis of chronic brucellosis. Among 27 patients with chronic and in the past serologically confirmed brucellosis in seven (25.9%) the presence of specific IgG anti-Brucella antibodies by ELISA was showed. Among all 15 patients presenting with clinical symptoms suggesting brucellosis and never serologically diagnosed presence of specific IgG antibodies to Brucella abortus by ELISA was not detected. Obtained results confirmed that humoral immunological response in patients infected in the past is running out and serological tests detecting specific antibodies in chronic brucellosis are useless. The ELISA test is an additional test in serological diagnosis of brucellosis. PMID- 11761838 TI - [Mortality of male members of the Polish olympic teams in 1981-1998]. AB - OBJECTIVE: Comparison of the mortality of male members of the Polish Olympic teams with the general Polish male population for the period 1981-1998 and for two sub-periods 1981-1991 and 1992-1998. METHODS: Statistical approach based on the follow-up method. Comparison with the reference population (Polish males from urban areas) was made by means of the standardized mortality ratios (SMRs) and their 95% confidence intervals. The series test (Wald-Wolfowitz test) was applied to assess the mortality difference in 1981-1991 and 1992-1998. MAIN OBSERVATIONS: A total number of 1,769 male members of the Polish Olympic teams were identified. Of those, 148 died before 1981 and 116 were excluded from the analysis because of incomplete data records. Finally analyzed cohort included 1,505 athletes of the age 14-99 years, who contributed 21,575.8 person-years of observation. 131 deaths were noted during the analyzed period. RESULTS: Calculated SMR for the analyzed group of sportsmen was 0.420; 95% confidence interval: 0.351-0.498. All age specific SMRs was lower than in general population. The athletes' mortality in 1992-1998 was significantly lower than in 1981-1991. CONCLUSION: Polish participants in Olympic Games were proved to exhibit significantly lower mortality than general Polish male population throughout their life. The decrease in sportsmen mortality decrease in 1992-1998 was stronger than observed for the reference population. PMID- 11761839 TI - [Validity study on the certification and coding of underlying causes of death for the mortality statistic]. AB - The study was designed to assess the differences in the quality of certification and coding practices of underlying causes of death, which the mortality statistics is based upon. The mains focus of the study was the problem of proper selection of the underlying cause of death in various diseases. In the analysis the potential impact of medical experience of the physicians and the hospitalization of patients before the death have been taken in consideration. There were 479 death certificates chosen randomly out of all certificates filled in by 240 medical doctors in 1999 in Krakow. For each death certificate the available clinical case histories for deceased persons have been collected in order that a team of medical experts could formulate their independent opinion about the underlying cause of death. From comparisons of the underlying causes of death from the death certificates with those of experts, the indices of agreement have been calculated. The best overall agreement has been found for the neoplasmatic diseases (83.1%) and the lowest for the chest diseases (30.7%). For cardiovascular diseases the overall agreement was 65.5%, however in coronary heart disease it reached 74.0% and in cerebrovascular diseases 78.7%. Generally, the better agreement has been demonstrated if the additional information about the coexistent diseases or direct causes of the death has been mentioned in the death certificates as well. The longer period of hospitalization of subjects before death was related significantly with the higher agreement indices. PMID- 11761840 TI - [Cervical cancer prevention - awareness and health behavior changes of women in 1976, 1986, 1990 and 1998]. AB - AIM: To find the changes in the proportion of women who declared knowledge about cytological tests and underwent that test in the years 1976, 1986, 1990 and 1998, as well as in the proportion of those who declared showing up at the gynaecologist during the last year. To assess the number of women taking part in the secondary prevention of cervical cancer. To correct health education intervention targeted at women. METHODS: The results of four cervical prevention surveys on representative samples of Polish women aged over 18 years were compared. RESULTS: The substantial (58%) increase in the proportion of women who declared awareness of cytological tests was shown. As expected, smaller favourable changes were found in the field of women's health related to secondary prevention. The percent of women who declared yearly visits at the gynaecologists increased by 12% and those who declared having cytological tests done during last three years by 7%. The lowest level of awareness and the lowest frequency of using prevention services were declared among women aged over 60, represented the lowest education level and resided in rural areas. CONCLUSIONS: It is important to continue educational work and intervention measures concerning cervical cancer prevention, with special attention to the most neglected groups of women. PMID- 11761841 TI - [An epidemiologic survey of multiple sclerosis in the Szczecin province in Poland]. AB - The possibility of a focus of the province of Szczecin (Northwestern part of Poland) was first noticed in our survey covering the period of 1960-86. Starting from 1986 the incidence of MS in this region was closely followed. Seven communes with an area of 1202 km2 and 45,231 inhabitants, had 50 MS patients on Dec. 31st, 1995 and a prevalence rate of 110,54/100,000. This is twice the prevalence more than in surrounding area (52,89/100,000). New cases appeared irregularly, with four peaks in 1960, 1967-8, 1976-7 and 1981-2. The age at onset, duration of disease, life expectancy and natural history of the disease in the focus and rest of Szczecin region were similar. We conclude, that clustering seems to be due to the influence of environmental factors, such as peat soil, coniferous forest, quality of drinking water and nearby industrial plants. PMID- 11761842 TI - [The reasons of low performance and delaying in the compulsory vaccinations of children. The methods of research]. AB - Regional differences in realisation of compulsory vaccinations of children in Poland are observed. The alarming low vaccine coverage had place in province of Cracow. The aim of the study was to explain the reasons of that situation in this area. Parents of unvaccinated children and their paediatricians were interviewed and detailed questionnaire was filled out. CONCLUSION: It is necessary to increase knowledge on vaccinology among physicians. PMID- 11761843 TI - [Performance of vaccinations against poliomyelitis and measles in Malopolska province versus the plan for eradication and elimination of these diseases]. AB - The requirements for elimination and eradication of measles and poliomyelitis have been presented. The basis criteria include achieving and maintaining 95% immunization rate of children less than 2 years of age in the entire country and in each individual province. The performance of vaccinations against measles and poliomyelitis in the Province of Malopolska has been analyzed. PMID- 11761844 TI - [Cerebellitis in the course of varicella in a child: case report]. AB - A case of cerebellitis as a complication of varicella in a 5-year old child was described. Special attention was paid to severe course of the disease and therapeutic problems. Actually available possibilities of active and passive prophylaxis of varicella-zoster virus infections were also discussed. PMID- 11761845 TI - [The organization, aims and tasks of the health service of the State Repatriation Department in years 1944-1950]. AB - Control of communicable diseases, particularly acute infections, among the repatriants was a crucial problem, in terms of medical care and the possibility of spreading diseases in the country. The establishment of a "sanitary cordon" was impossible both due to difficulties in sanitation and to the massive and chaotic repatriation in the periods after end of war. Therefore a number of special camps were organized on the various-main repatriation entrance points, and within the country, especially in territories where the repatriants settled i.e. the Western Provinces. In the four most important entrance points isolation hospitals were organized. The repatriant camps were also provided with drugs, equipment and means of disinfection. Health Section of the State Repatriation Department (PUR) was creating its own health service for the repatriants in the years 1944-1950. Its relation to repatriation were limited to general epidemiological supervision, providing funds for treatment of repatriants suffering from communicable diseases and the partial provision of medical supplies to the PUR facilities. PMID- 11761846 TI - [Bioterrorism]. AB - Some countries explore biological agents (toxins, bacteria and viruses) as a potential threat that can be used as a weapon of mass destruction. The list of a biological and chemical weapons is still expanding. Despite military aspect of the issue, medical and civil staff must be aware that also an act of bioterrorism could happen. We must not be afraid, but we must be prepared. PMID- 11761847 TI - A brief overview of bovine spongiform encephalopathy and related diseases including a TSE risk analysis of bovine starting materials used during the manufacture of vaccines for use in humans. PMID- 11761848 TI - [Construction of eukaryotic expression plasmid for mouse myogenic regulatory factor MyoD gene]. AB - OBJECTIVE: To construct eukaryotic expression plasmid of mouse myogenic regulatory factor MyoD gene for further study on MyoD gene function in molecular regulatory mechanism in skeletal muscle repair. METHODS: The plasmids PEMMBC2 beta 5 containing full cDNA length of MyoD inserted in EcoRI restriction site, were first propagated in Escherichia coli DH5a, then extracted and purified with the Wizard Plus Minipreps DNA Purification System (Promega, USA). The coding sequence of MyoD in PEMMBC2 beta 5 was confirmed by agarose gel electrophoresis and DNA sequence analysis. After plasmids PEMMBC2 beta 5 and plasmids pcDNA3-neo were prepared by digestion with EcoRI, the MyoD cDNA fragment was inserted into EcoRI site in pcDNA3-neo eukaryotic expression vector, and pcDNA3/MyoD was formed. The pcDNA3/MyoD, digested with restriction enzymes, was found to contain the MyoD cDNA sequence by agarose gel electrophoresis analysis. RESULTS: The extracted and purified PEMMBC2 beta 5 contained the correct nucleotide sequence for the full length of MyoD cDNA fragment. The MyoD cDNA fragment had been inserted into the eukaryotic expression plasmid pcDNA3-neo, which formed the pcDNA3/MyoD. CONCLUSION: The pcDNA3/MyoD, a eukaryotic expression plasmid, for MyoD is constructed successfully. PMID- 11761849 TI - [The proliferation and differentiation of primary human embryonic skeletal myoblasts]. AB - OBJECTIVE: To observe the proliferation and differentiation properties of primary human embryonic skeletal myoblasts cultured in vitro. METHODS: The skeletal muscle samples were obtained from 20 to 25-week abortion fetus, the family history of inherited myopathies of parental generation was negative. With a modified method of Blau, the muscle sample was digested with trypsin and collagenase. The isolated cell suspension was a mixture of myoblasts and fibroblasts, the latter was removed by repeated attachment to culture dishes. The morphological, immunohistochemical observation, the proliferation and differentiation of primary myoblasts were studied. RESULTS: The isolated myoblasts were spherical in cell suspension and spindle-like after attached to culture dishes. The myosin specialized immunohistochemical staining was strongly positive. A large quantity of skeletal muscle specialized creatine kinase (CK-MM) was synthesized in cultured myoblasts. Additionally, while the cell density of myoblasts increased, the monocyte myoblasts would fused to form multinucleated myotube. All those indicated that the cultured cells were myoblasts. Primary myoblasts proliferated quickly, the doubling time, measured in growth curve, was 4.8 days. CONCLUSION: A large number of myoblasts can be available with digestion and repeated attachment method. The cultured cells can be proved as myoblasts by morphological and immunohistochemical detection. The cultured myoblasts have good ability of proliferation and differentiation. PMID- 11761850 TI - [Culture of human muscle satellite cell]. AB - OBJECTIVE: To investigate the biological characteristics of human muscle satellite cell cultured in vitro. METHODS: Human muscle satellite cells were obtained from skeletal muscle biopsies of six patients during corrective orthopedic surgery, cultivated in growth medium for ten days, then in differentiation medium for additional five days. Human satellite cells were identified with monoclonal antibody against desmin. Cells were observed under phase contrast microscopy. RESULTS: Human muscle satellite cells proliferated in growth medium, and fused to form myotubes in differentiation medium. After 24 hours in differentiation medium, the confluent satellite cells began to fuse actively and achieved the top level at 72 hours. CONCLUSION: Human muscle satellite cell can proliferate and differentiate in appropriate culture condition. Immunocytochemical detection of desmin is the effective early method to determine satellite cell. PMID- 11761851 TI - [Study on improvement of cell affinity of polymer materials--modified poly(D,L lactide) by anhydrous ammonia gaseous plasma]. AB - OBJECTIVE: To modify the surface of poly(D,L-lactide) film by anhydrous ammonia gaseous plasma treatment. METHODS: The changes of contact angles were measured and surface energy were calculated. Mouse 3T3 fibroblast cells were cultured on plasma modified and control poly(D,L-lactide) films. RESULTS: It was found that the hydrophilicity and surface energy of the materials have been increased after plasma treatment. Cell culture results showed that ammonia plasma treatment could promote the cell attachment and cells growth. After 4 days culture, the cells on the plasma treated films were 2-folds quantitatively compared with that of the control films. CONCLUSION: Ammonia plasma treatment can improve the cell affinity to poly(D,L-lactide). PMID- 11761852 TI - [Formation of the allogeneic tissue engineered cartilage using injectable biomaterial]. AB - OBJECTIVE: To study the feasibility of the formation of allogeneic tissue engineered cartilage of certain shape in immunocompetent animal using the injectable biomaterial. METHODS: Fresh newborn rabbits' articular cartilages were obtained under sterile condition (< 6 hours after death) and incubated in the sterile 0.3% type II collagenase solution. After digestion of 8 to 12 hours, the solution was filtered through a 150 micron nylon mesh and centrifuged, then the chondrocytes were washed twice with phosphate buffered saline (PBS) and mixed with the biomaterial to create a final cell density of 5 x 10(7)/ml. The cell biomaterial admixture was injected into rabbits subcutaneously 0.3 ml each point while we drew the needle back in order to form the neocartilage in the shape of cudgel, and the control groups were injected with only the biomaterial or the suspension of chondrocytes with the density of 5 x 10(7)/ml. After 4, 6, 8 and 12 weeks, the neocartilages were harvested to analyze. RESULTS: The new nodes could be touched subcutaneously after 2 weeks. In the sections of the samples harvested after 4 weeks, it was found that the matrix secreted and the collagen formed. After 6 weeks and later than that, the neocartilages were mature and the biomaterial was almost completely degraded. The cudgel-shaped samples of neocartilage could be formed by injection. In the experiment group, there was no obvious immune rejection response. On the contrary, there were no neocartilage formed in the control group. CONCLUSION: The injectable biomaterial is a relatively ideal biomaterial for tissue engineering, and it is feasible to form allogeneic tissue engineered cartilage of certain shape by injection in an immunocompetent animal. PMID- 11761853 TI - [Study on chitosan-gelatin/hydroxyapatite composite scaffolds--preparation and morphology]. AB - OBJECTIVE: To prepare chitosan-gelatin/hydroxyapatite (CS-Gel/HA) composite scaffolds, and to investigate the influence of components and preparing conditions to their micromorphology. METHODS: The CS-Gel/HA composite scaffolds were prepared by phase-separation method. Micromorphology and porosity were detected by using scanning electron microscope and liquid displacement method respectively. RESULTS: Porous CS-Gel/HA composite scaffolds could be prepared by phase-separation method, and their density and porosity could be controlled by adjusting components and quenching temperature. CONCLUSION: The study suggests the feasibility of using CS-Gel/HA composite scaffolds for the transplantation of autogenous osteoblasts to regenerate bone tissue. PMID- 11761855 TI - [Advances of construction of tissue engineered blood vessels]. AB - OBJECTIVE: To discuss the approaches of tissue engineered blood vessels (TEBV) reconstruction. METHODS: The recent literatures about TEBV were widely reviewed. We summarized various types of biomaterials served as scaffold for TEBV and evaluated the construction model of TEBV. And the biological properties of some TEBV were compared. RESULTS: Although the final model of construction of TEBV was not clear, reports in the last two years had shown several important advances in this exciting field. CONCLUSION: Mimicry of some or all of the properties of three layers of natural healthy blood vessels has been the strategy of all TEBV approaches. PMID- 11761854 TI - [Research and application of drug controlled release technique in tissue engineering]. AB - OBJECTIVE: To investigate protection of biological activity and controlled release of growth factor by means of drug controlled release technique in tissue engineering. METHODS: Using drug controlled release technique that to embed or microcapsulate the biological drug with biodegradable polymer. RESULTS: The aliphatic polylactone could be used as drug carrier for each drug including the biological matter. And the release behavior of the drug could be controlled by adjusting the molecular structure of the carrier and the controlled release method. The successful example, that to realize regeneration of rat's sciatic nerve with 5, 10, 15 and 20 mm of gap by using polylactide as nerve guide and the embedding growth factor, had been obtained. CONCLUSION: It is possible to realize protection of biological activity and sustained release of growth factor by using aliphatic polylactone as drug carrier. PMID- 11761856 TI - [Advance on repair of growth plate injury]. AB - OBJECTIVE: To sum up the studying course and latter development of repair of injury of growth plate. METHODS: Recent original articles about repair of injury of growth plate were extensively reviewed, focused on the progresses in understanding repair of injury of growth plate and comparison of several major reparative methods. RESULTS: Repair of injury of growth plate is a great difficulty in experimental study and clinical treatment of pediatric orthopedics. Graft of free growth plate and cartilage were unfavorably used because of lack of blood supplement. Although graft of vascularized growth plate solved circulation problem, both two kinds of grafts were involved in limitation of donor and immunologic reaction. Non-cartilaginous tissue and material could only prevent formation of bony bridge in small defect of growth plate and lacked ability of regenerative repair. Transfer of tissue engineered cartilage might be the best choice for repair of injury of growth plate. CONCLUSION: Considering source of transplanted material, reparative effect and adverse reaction, repair of injury of growth plate with tissue engineered cartilage deserves further investigation. PMID- 11761857 TI - [The stimulating effects of bFGF on fibroblast function and its C-fos gene expression]. AB - OBJECTIVE: To study the stimulating effects of basic fibroblast growth factor(bFGF) on fibroblast function and its ability to expression of c-fos gene. Furthermore, to explore the possible network action between bFGF and oncogene in modulating wound healing. METHODS: Cultured rat fibroblasts were divided into bFGF stimulating group and control group. Fibroblasts in bFGF stimulating group were treated with bFGF in a dosage of 40 ng/culture hole, while the control fibroblasts were treated with the same vehicle without bFGF. The morphology, cell vitality and their ability to express c-fos gene in the fibroblasts in both groups were studied with MTT and immunohistochemical methods. RESULTS: All fibroblasts in bFGF treated groups were enlarged and showed increased vitality with MTT method. C-fos gene expression in bFGF stimulating group was increased, especially in nucleus when compared with those in control group. CONCLUSION: The results show that the function and the ability to express c-fos gene in bFGF treated fibroblasts are enhanced. Combined with our previous studies, it may make a conclusion that there is a network regulation mechanism between growth factors and some oncogenes. PMID- 11761858 TI - [Repair and reconstruction of massively damaged wounds]. AB - OBJECTIVE: To report repair and reconstruction of massively damaged wound under unusual condition. METHODS: One hundred and forty-seven patients with deep tissue defects were admitted from January 1993 to December 2000, among them, 96 cases suffered from electrical injury, 18 cases with hot press injury, 18 cases with deep burns as a result of CO poisoning or epileptic seizure, 6 cases caused by chemical producing necrosis and wound infection, 3 cases with radiation injuries, 2 cases with chemical burn, 2 cases with explosive injury, 2 cases with frostbite. One hundred and seventy five wounds in 147 patients were repaired by transfer of local flap, forearm conversal island skin flap, pectoralis major myocutaneous flap, delto-pectoral skin flap, latissimus dorsi skin flap, gastroecnemius myocutaneous flap, anterior and posterior tibial artery island skin flap, and so on. The wound defect ranged from 1 cm x 1 cm to 20 cm x 28 cm, and the flaps were 1.5 cm x 2.0 cm to 22 cm x 30 cm. The necrotic tendon was replaced with acellular allogenic tendon simultaneously in 7 cases. RESULTS: One hundred and sixty-nine flaps were survival with first intention, while necrosis of the tip of flap occurred in 6 cases. The transplantation of acellular allogenic tendon in all cases were survival. The function and configuration in 28 cases were satisfactory after 4 months to 8 years follow-up. CONCLUSION: Various types of flaps are choosen according to the position, defect range and degree of wound, which is an ideal method to restore the function and to improve patients' living condition. PMID- 11761860 TI - [Experimental study on repair of bile duct defects with expanded polytetrafluoroethylene]. AB - OBJECTIVE: To explore the possibility of repair of the extensive bile duct injuries with expanded polytetrafluoroethylene (ePTFE). METHODS: A total of 36 local healthy hybrid dogs were employed to establish bile duct injury models by means of partial removal of bile duct (group A, 14 dogs), excision of a segmental duct (group B, 10 dogs), and ligation of the lower part of common bile duct(group C, 5 dogs; group D, 7 dogs). Group A were patched with ePTFE mesh, group B replaced by ePTFE tube. Interposition of the grafts between gallbladder and duedenum or jejunum was performed on group C and group D. The animals' postoperative performance status were evaluated. Cholangiography was used to define the patency of bile ducts. Tissues of bile ducts and liver were taken at 3 days, 2, 4, 8, 12 and 52 weeks for microscopic and ultrastructural examination to observe the healing process of bile duct and morphological changes in the liver. RESULTS: Group A with ePTFE patch covered by epithelium had a high patency rate of 75%(9/12) and pathological damages were not found in the liver. The patency rate of group B was merely 40%(4/10), to some extent, accompanying damages in the liver. The grafts of group C and group D were fully expelled, ultimately leading to cystic-duodenal or cystic-jejunal fistulas formation. CONCLUSION: The study suggests that application of ePTFE patch to repair bile duct defects is feasible. PMID- 11761859 TI - [Effects of ANSON NANOTECH on the healing of cutaneous chronic wounds]. AB - OBJECTIVE: To observe the effects of ANSON NANOTECH on the healing of cutaneous chronic wounds. METHODS: Thirty-four cases with 44 wounds were locally treated with ANSON NANOTECH in the wounds after debridement. Among them, there were 15 cases with traumatic ulcer (23 wounds), 9 cases with pressure ulcer(11 wounds), 5 cases with diabetes ulcer, and 5 cases with radiation ulcer. The healing time of wounds was used to evaluate the treatment results. RESULTS: The healing time in all of chronic wounds were accelerated. All wounds from trauma, diabetes and pressure were healed within 4 weeks and another 2 wounds from radiation injuries were healed over 4 weeks. The healing rate within 4 weeks was 95.5%. CONCLUSION: The results indicate that ANSON NANOTECH can accelerate the healing of chronic wounds. The mechanism probably include sterilization, improvement of local microcirculation, promotion of cell growth, and so on. PMID- 11761861 TI - [Design of Z-shaped Achilles tendon scar composite flaps to correct the tendon scar contracture]. AB - OBJECTIVE: To modify the design of the Achilles tendon-scar composite flap into the Z-shape and to apply it into clinic situations to correct the tendon-scar contracture after burn and other injures. METHODS: According to degree of contracture and strephenopedia, the central limb of Z-shaped design lay in contracture line of posterior ankle area just over the Achilles tendon and extended 8 to 12 cm in length. Lateral limbs extended 5 to 8 cm and usual angles of the Z-shape was 60 degrees. The two tendon-scar composite flaps were made and slipped along the central limb between them. From March 1994 to August 1999, seven patients with Achilles tendon scar contracture were operated with this method. RESULTS: Excellent relieving of the Achilles tendon-scar contractue was achieved. No such complications happened as ischemia and necrosis of the flaps. CONCLUSION: The Z-shaped tendon-scar composite flap is practical in clinics. It is characterized by abundant blood supply, easily procedure and reliable result. PMID- 11761862 TI - [Repair of humeral fracture and non-union with transfer of vascularized periosteal flap]. AB - OBJECTIVE: To study the results of humeral fracture and non-union repaired by vascularized periosteal flap transfer. METHODS: The clinical data of humeral fracture and non-union in 23 cases were analysized retrospectively since 1995. Among them, minuted or several segmental fracture in 12 cases, non-union in 11 cases, and following injury of radial nerve in 7 cases. The operative method was open reduction, inner or external fixation with vascularized periosteal flap transfer. RESULTS: The period of follow-up was 6 months to 2 years. The repair result of all patients was excellent and good, but elbow joint motion in 2 cases of non-union was not satisfactory. The periosteal flap had good osteogenic ability. The period of bone union was 2 to 5 months in humeral fracture and non union. And function of radial nerve was recovery. CONCLUSION: Transfer of distal humeral periosteal flap pedicled with radial collateral vessels is a better method for humeral fracture and non-union. PMID- 11761863 TI - [Comparative study of microvascular anastomotic clips and suture in small vessel anastomosis]. AB - OBJECTIVE: To explore an ideal way of small vessel anastomosis for microsurgery. METHODS: Anastomosis of both carotid arteries were performed in 20 rabbits. One side of the arteries were anastomosed with anastomotic clips, the other side of the arteries, as comparison, were anastomosed with suture. The vessels were harvested at first and 14th day after operation and were evaluated using operating microscope, light microscope and electronic microscope. RESULTS: The average anastomotic time for suture was about 15 minutes, while for the clips was 2 to 5 minutes. There were no difference in patency between the two techniques. Endothelialization at the anastomotic sites were both completed 14 days postoperatively. However, for the anastomotic clips, there were no endothelia damage and foreign bodies formation inside the vessels. CONCLUSION: This experiment has confirmed that the anastomotic clip's procedure provides a very safe and easy way to perform anastomosis and reduce the incidence of thromboses. PMID- 11761864 TI - [Experimental study on functional rehabilitation of peripheral nerve with electric acupuncture]. AB - OBJECTIVE: To observe the functional rehabilitation of injured peripheral nerve with electric acupuncture. METHODS: Sciatic nerve injury model was established by transection of left sciatic nerve in 60 Wistar rats, which were randomly divided into two groups. The experimental group was treated with electroacupuncture, no treatment in the control group. Change of nerve electrophysiological, power of muscle and sciatic functional index (SFI) were observed. RESULTS: Nerve muscle action potential (MAP) and motor nerve conduction velocity (MNCV) in the experimental group were better than that of the control group (P < 0.01). The single muscle twitch and tetanization of gastrocnemius muscle were higher in the experimental group too (P < 0.05). SFI were significantly higher in the experimental group (P < 0.05). CONCLUSION: Electric acupuncture therapy can improve functional rehabilitation of injured peripheral nerve. PMID- 11761865 TI - [Use of intraoperative red blood cell salvage in the anterior stabile operation of spinal fracture]. AB - OBJECTIVE: To observe the clinical results in the anterior stabile operation of spinal fracture using red blood salvage. METHODS: Nineteen cases with spinal fracture were performed the anterior decompress operation. Blood cell salvage were used during operation. Other 20 cases were also reviewed as control group, who were received the same operation without blood cell salvage. RESULTS: In the 19 cases, average volume of autologous transfusion was 536 ml. Only two cases had homologous transfusion requirements. In the control group, all cases needed homologous transfusion (averaged 947 ml). CONCLUSION: In the anterior decompress operation, the intraoperative blood salvage is highly effective in reducing transfusion and also improves the security of operation. PMID- 11761866 TI - Changes that impact upon health care: what do you know? PMID- 11761867 TI - War time experiences of triage and resuscitation: Australian Army nurses in the Vietnam War, 1967-1971. AB - The experiences of nurses in war is prolifically described in the North American scholarly literature, and in the Australian nursing literature to a lesser extent. The literature describes the plights and achievements of nurses caring for soldiers and civilians often under the most undesirable of circumstances. A central focus of war time nursing is the resuscitation of critically wounded soldiers. This paper addresses the experiences of the Australian Army nurses who were involved in the triage and resuscitation of critically wounded allied and enemy soldiers in the Vietnam War between 1967 and 1971. As part of a research study to explore and analyse the nature of nursing work in the Vietnam War, seventeen Vietnam veteran nurses were interviewed about their experiences. This paper explores the progression of the triage department in the Australian military hospital in Vung Tau, and it highlights that the majority of the nurses who took part in this study were clinically unprepared, particularly as emergency nurses. PMID- 11761868 TI - Effect of cutaneous stimulation on pain reduction in emergency department patients. AB - CONTEXT: The problem of unrelieved pain in Emergency Department (ED) patients as well as contraindications to analgesics and narcotics due to masking of symptoms during the diagnostic period, presents itself as a unique opportunity for ED nurses to utilize non-pharmacological and non-invasive interventions such as cutaneous stimulation (CS) to relieve pain. OBJECTIVE: To evaluate the effectiveness of a specific protocol of CS, developed by the researchers, in reducing pain levels in ED patients. Another objective was to determine the effect of CS on blood pressure and heart rate. Potential factors that could influence the dependent variables such as age, gender, educational level, location of pain, and site of CS were tested. DESIGN: A one group pre-test post test experimental design measured variables before and after intervention in all subjects. SAMPLE: After being screened for inclusion, 50 patients (38 adults, 12 children) were admitted to the study and were treated with CS to relieve pain. RESULTS: Following CS, subjects reported significantly reduced pain, and demonstrated reduced heart rate, and blood pressure readings. The location of pain significantly influenced heart rate and diastolic blood pressure but not pain level. The most effective site of CS was contralateral to the pain. Age, gender and educational level had no significant affect. CONCLUSIONS: The results of this study provide empirical evidence that CS effectively reduces pain, heart rate, and blood pressure in ED patients. The intervention of CS has solid utilization potential and could be easily incorporated into standard ED procedure. Further research is needed to identify threats to internal validity especially that of the caring presence of the nurse. PMID- 11761869 TI - Telephone triage: an Irish view. AB - This paper examines the issue of telephone triage for an Irish Emergency Department and includes definitions of triage and telephone triage. At St. James Hospital, Dublin the first attempt at formal telephone triage failed. In hindsight this was attributed to inadequate research into the topic and lack of staff motivation. This paper forms part of a larger literature review undertaken by the author following the first failed attempt. An overview of the international literature addresses both the positive and negative sides of a telephone helpline. The body of literature reviewed suggests telephone triage can be successful but advises the use of formal protocols, training of staff and accurate documentation. The purpose of this paper is therefore to investigate the benefits and recommended practices of implementing telephone triage with a view to successfully changing policy and practice in a busy Emergency Department. PMID- 11761870 TI - Problem-based learning: a gynaecological dilemma. PMID- 11761871 TI - Dilemma. TV programme in A&E. PMID- 11761872 TI - The mental health nurse: contributing to improved outcomes for patients in the emergency department. AB - Fundamental changes to health-care policy in Australia have led to an increase in the extent to which emergency department staff come into contact with patients experiencing mental health problems. This has been problematic for nurses, many of whom perceive themselves as lacking the skills and expertise to provide appropriate care and treatment to this client group. Psychiatric/mental health consultation-liaison nursing within the emergency department is becoming established as a means to overcome some of the problems identified. Despite this growth there is a paucity of literature evaluating the effectiveness of this position. This paper presents the results of an evaluation of the mental-health consultation-liaison nurse role in an inner city teaching hospital in Sydney Australia. The survey involved a three stage approach to data collection. The data collected at the commencement of the position included focus groups to ascertain the needs of emergency department nurses and a questionnaire designed to measure the skills, confidence and perceived knowledge of emergency department nursing and medical staff. An evaluation of the satisfaction of nurses and doctors was conducted towards the end of the three month pilot programme. The results confirmed the need for positions of this type and suggested a high level of satisfaction with the service provided. PMID- 11761873 TI - Assessment tools: are they an effective approach to implementing spiritual health care within the NHS? AB - Over the last 25 years, many nursing and palliative care journals have carried articles on the subject of 'spiritual' health care. The following is a review of National Health Service (NHS) guidelines and the work of various writers who have contributed to the debate on 'spirit' and 'spiritual needs' from within sociology, palliative care and nursing studies. However, 'spiritual' in the current usage should not be confused with 'religious' and is part of an understanding of what is known as holistic nursing (Dossey et al. 1995). This paper will examine what is meant by 'spiritual' and religious needs and what is indicated by the words 'spiritual' and 'spirit'; and some of the implications for a health care team will be considered. The place of assessment tools in 'spiritual' health care, and the role of the NHS chaplain in the assessment and provision of 'spiritual' health care will be examined. PMID- 11761874 TI - When is a bed not a bed? PMID- 11761875 TI - Pedestrian road traffic collisions in South Africa. AB - Pedestrian road traffic collisions continue to account for a large number of the clients attending the accident & emergency units in South Africa. These victims include both adults and children, and can lead to serious lifelong consequences for the victims and their families. A pilot study was carried out in Durban, KwaZulu-Natal in order to investigate the injuries sustained by pedestrian paediatric clients who were involved in road traffic collisions in South Africa. The findings of the study reflecting the age, gender distribution and the injuries and their severity are discussed. PMID- 11761876 TI - Contribution of a lecturer-practitioner in implementing evidence-based health care. AB - This article describes and discusses the role of a lecturer-practitioner (LP) in the context of a university and practice development unit within a primary care trust in contributing to evidence-based health care. Evidence-based health care is currently high on the political and professional agendas. Methods employed in practice to create an environment that encourages and supports innovation will be described. Methods used in the educational establishment will also be highlighted from a theoretical and practice perspective. Progress to date and expected future outcomes will be shared. The article concludes that progress is dependent on all those involved, sharing common goals in the implementation of evidence based health care as it will continue to remain high on the agenda in the educational and service sectors. This drive towards clinical effectiveness and evidence based practice puts the LP in an ideal position to reduce the practice-theory gap by the nature of their integrated role. PMID- 11761877 TI - Sign of the times or the shape of things to come? A 3-day unit of instruction on 'aggression and violence in health settings for all students during pre registration nurse training'. AB - In the UK, figures based on a recent survey of NHS Trusts suggest that health care workers are at greater risk (four times higher than normal) from work related violence than the general population. Studies also show that, of all health professions and grades, student nurses are at the greatest risk of being the victim. Yet, training in self-protection and pro-active management of aggression and violence remains predominantly a post-registration preserve. Despite English National Board (1993) recommendations recognizing that all pre registration courses for nurses and midwives should contain material on aggression and violence delivered by appropriately qualified trainers and teachers, this input is still likely to be uncoordinated and disparate within curricula. This paper reports the design, and early experience of delivery, of an integrated, 3-day unit of instruction for pre-registration students within a Common Foundation Programme of a diploma-level course. The unit designer/leader is a University Lecturer and Royal College of Nursing (RCN) Institute Registered Trainer in the management of actual and potential aggression. Consequently, all aspects involving teaching physical skills (breakaway skills) adhere to the recently published RCN training standards. In addition, initial student feedback on the delivery and suitability of the unit will be presented, along with a discussion of related issues. PMID- 11761878 TI - [Studies on the mechanism of persistent infection of Helicobacter pylori]. PMID- 11761879 TI - [Molecular genetic study of pathogenesis of the oral anaerobic bacterium Porphyromonas gingivalis]. PMID- 11761880 TI - [Iron uptake mechanism of periodontopathogens with special regards to Porphyromonas gingivalis]. PMID- 11761881 TI - [Grand design for health care in 21st century]. PMID- 11761882 TI - [EBM and asthma prevention and management guidelines]. PMID- 11761883 TI - [Meta-analysis of pharmacotherapies for allergic rhinitis]. AB - We performed meta-analysis using the data in literatures of the clinical study related to pharmacotherapies for allergic rhinitis in Japan as evidences. We extracted double-blind studies which used first-generation antihistamines, early stage second-generation antihistamines, late-stage second-generation antihistamines and arachidonic acid metabolite-receptor antagonists as investigational drugs. In meta-analysis of first-generation antihistamines and early-stage second-generation antihistamines, significant differences between them were detected in final overall improvement and usefulness. In meta-analysis of early-stage second-generation antihistamines and late-stage second-generation antihistamines, significant differences between them were detected in usefulness and sleepiness as an adverse effect. In meta-analysis of late-stage second generation antihistamines and arachidonic acid metabolite-receptor antagonists, significant differences between them were detected in final overall improvement and usefulness. These results indicate a historical trend in the development of drugs including measures to deal with sleepiness as an adverse effect. The arachidonic acid metabolite antagonists appeared to be promising among the oral drugs for allergic rhinitis, although data related to the arachidonic acid metabolite antagonists are still few and further collection of them is necessary. PMID- 11761884 TI - [Analysis of factors influencing on Anisakis specific IgE antibodies]. AB - Anisakis-specific IgE (AsIgE) was examined in 84 cases of acute urticaria (AU) and 100 cases of atopic dermatitis (AD). Gender, age, disease category (AU or AD) and serum IgE value of the patients were compared with AsIgE. Univariate analysis showed that there was significant correlation between age and AsIgE, and between serum IgE and AsIgE. Serum IgE was significantly higher in AD than in AU. Age was significantly higher in AU than in AD. AsIgE was positive value in 26 cases (31%) of AU and 25 cases (25%) of AD. There were no significant differences between them. In these cases, however, AsIgE was significantly higher in AU than in AD. Percentage of patients with high AsIgE value (> class 2) was significantly higher in AU (20 cases, 24%) than in AD (3 cases, 3%). Multivariate analysis using discriminant analysis and logistic regression analysis showed that the most influential factor on AsIgE was disease category (relative risk = 16.87), and the second was age (relative risk = 1.05). Serum IgE and gender were considered not to influence on AsIgE. It is possible that Anisakis or related antigens have something to do with urticaria in AU patients with high AsIgE value. PMID- 11761885 TI - [Clinical significance of measurement of urinary leukotriene E4 in asthmatic patients without attack]. AB - To evaluate clinical significance of measurement of urinary leukotriene E4 (LTE4) in asthmatic patients without attack, we measured urinary LTE4 in 68 asthmatic patients without attack and investigated its correlation with severity of asthma, % FEV1, bronchial hyperresponsiveness and peripheral eosinophil counts. Values of urinary LTE4 were significantly higher in the asthmatic patients (113.6 +/- 9.7 pg/mg.cr) than in healthy control subjects (67.8 +/- 4.7, n = 31), and the level of urinary LTE4 was in proportion to the severity of disease. Urinary LTE4 showed significant negative correlation with % FEV1 in atopic patients (Rs = -0.43, p = 0.025, n = 28), which was not recognized in non-atopic patients. Urinary LTE4 showed no significant correlation with bronchial hyperresponsiveness and peripheral eosinophil counts. Our findings suggested that basal LTE4 in urine reflected chronic airway inflammation of asthma. PMID- 11761886 TI - [The study of 18 cases of aspirin urticaria at dermatology of Yodogawa Christian Hospital--on the difference between aspirin asthma and aspirin urticaria]. AB - Aspirin intolerance manifests itself as two clinical symptoms, urticaria/angioedema and asthma. However, there is seldom patient of aspirin intolerance who has the both symptoms, urticaria and asthma. So we suspect that the pathogenic mechanism for aspirin urticaria differs from that for aspirin asthma. We examined 18 patients of aspirin urticaria at dermatology of Yodogawa Christian Hospital, especially as to oral aspirin challenge test. All patients had no symptom of asthma. Threshold dose evoke urticaria/angioedema after ingesting 100 to 500 mg of aspirin (average, 311 mg). Urticaria/angioedema occurred within 50 minutes to 14 hours (average, 3 hours 16 minutes) after ingesting aspirin. The dose and the time of oral aspirin challenge test for these 18 patients were more spent than those for reported patients of aspirin asthma. These results support the opinion that aspirin urticaria has the different pathogenic mechanism from aspirin asthma. In addition, we experienced one patient of aspirin intolerance which caused hyperemia and edema of the bulbar conjunctiva. She had no symptom of urticaria and asthma, and had the both character of aspirin urticaria and asthma as to aspirin challenge test. We propose that aspirin intolerance is classified in reaction of the skin (urticaria/angioedema) and reaction of the mucosa (asthma), and it has an intermediate type. PMID- 11761887 TI - [Clinical usefulness of the histamine release test in assessing adult asthmatic patients who keep hamster]. AB - Recently, the prevalence of keeping pets, such as hamsters and guinea pigs, at home has been increasing in Japan. The number of adult asthmatic patients who keep hamster (HKA) has increased, and accounted for 20% of all pet owners in 1997. Histamine release tests (HRT) were performed on 28 patients of HKA, who consulted with the outpatient clinic of our department, and the results were compared with CAP-RAST. HRT were performed with peripheral blood obtained from each subject, and histamine content was measured by fluorescent assay. 7 in 12 RAST positive patients and 4 in 16 RAST negative patients in HKA had histamine release titer reaction over 15 ng/ml. HRT and CAP-RAST scores were correlated in HKA, and HRT could be evaluated before and after stopping keeping hamsters in five subjects to find decreased HRT scores in all. The results obtained indicate that those tests were useful for the clinical diagnosing and monitoring of HKA. PMID- 11761888 TI - [Rational lymph node dissection for lung cancer according to the occurrence lobe and histological type]. AB - Between January 1989 and December 1998, 134 cases of squamous cell carcinoma and 244 cases of adenocarcinoma underwent surgical resection of the lung with systematic lymph node dissection in our hospital. The cN diagnosis by CT scan and pN diagnosis were compared. In squamous cell carcinoma pN 2-3 cases were only one patient (2%) out of 60 patients with cN 0, 5 patients (18%) out of 28 patients with cN 1, and 21 patients (46%) out of 46 patients with cN 2-3. On the other hand in adenocarcinoma pN 2-3 cases were 27 patients (14%) out of 193 patients with cN 0, 3 patients (25%) out of 12 patients with cN 1, and 24 patients (62%) out of 39 patients with cN 2-3. The pathways of the lymphatic metastases to the mediastinal nodes were analized in 27 patients with squamous cell carcinoma and 54 patients with adenocarcinoma undergoing systematic lymph node dissection. All patients had histologically proven mediastinal metastasis. Histologically there was no difference in pathways of the lymphatic metastases to the mediastinal nodes. 1. The dominant lymphatic drainage from the right upper lobe flowed into the superior mediastinal nodes. The direct metastatic passages to the superior mediastinal nodes were observed (47%). Subcarinal and inferior mediastinal node involvement was rare (3%). 2. The dominant lymphatic drainage from the middle and the lower lobe flowed into the subcarinal nodes (85%). The involvement of the superior mediastinal nodes occurred in 53% of subcarinal node positive patients on the right side. 3. The dominant lymphatic drainage from the left upper lobe flowed into the subaortic or paraaortic nodes (69%). Subcarinal and inferior mediastinal node involvement was rare (6%). We conclude that subcarinal and inferior mediastinal lymph node dissection is not necessary for upper lobe lung cancers, and that superior mediastinal lymph node dissection can be omitted in middle and lower lobe lung cancers without hilar and subcarinal lymph node involvement, especially in the cases of cN 0. PMID- 11761889 TI - [Two successful cases of coronary artery bypass grafting followed by transluminal carotid angioplasty with stenting]. AB - In coronary artery bypass grafting (CABG), carotid artery disease is an important factor that affects the incidence of perioperative stroke. The incidence of stroke following cardiac surgery is about 5 times higher in patients with carotid lesions than in patients without them. However, therapeutic strategies for those cases have not established in recent years. We report 2 successful cases of CABG following transluminal carotid angioplasty with stenting (TCAS) for concomitant coronary and carotid artery disease. The first case was a 71-year-old male who had left main trunk (LMT) and three-vessel coronary artery disease (CAD) and a 90% stenosis of the right internal carotid artery (ICA). One month after TCAS, triple CABG with cardiopulmonary bypass (CPB) was performed. The second case was a 75-year-old male who had LMT and single vessel CAD and a 99.9% stenosis of the lt. ICA. Considering his poor general conditions, combined strategy of off-pump CABG and PTCA was performed following TCAS. During and after cardiac surgery, they had no cerebral complications. Postoperative myocardial scintigraphy showed improved imaging in both cases. Preoperative TCAS is a safe and minimally invasive procedure for the patients with carotid artery stenosis who need CABG. PMID- 11761890 TI - [Mitral valve replacement 41 years after right pneumonectomy]. AB - Mitral valve replacement was performed successfully on a 68-year-old patient who had undergone right pneumonectomy and thoracoplasty 41 years earlier. Preoperative pulmonary function tests revealed poor results; the forced vital capacity was 950 ml (28.0% of the predicted value) and the forced expiratory volume in 1 second was 750 ml (28.9% of the predicted value). Despite such poor pulmonary function, the patient tolerated the operation well and led uneventful course. Careful perioperative management to prevent pulmonary edema and aggressive postoperative pulmonary toilet to facilitate recovery of the pulmonary function seem important. PMID- 11761891 TI - [A case of right pneumonectomy and omentopexy for lung cancer after preoperative irradiation]. AB - A 72-year-old man complaining of cough rejected the operation for squamous cell carcinoma obstructing the right intermediate trunk, therefore he was received 82 Gy (40 Gy and 42 Gy) of radiotherapy. However, the tumor did not decrease, in addition, cough and purulent sputum became severe gradually. We performed right pneumonectomy and omentopexy to prevent bronchial fistula, he had no pulmonary complication. Radiotherapy is a risk factor for postoperative bronchial fistula, omentopexy is useful to prevent it. PMID- 11761893 TI - [A case of refractory spasm of multiple coronary arteries and left internal thoracic artery graft following off-pump CABG]. AB - A 61-year-old man with exertional angina was underwent off-pump CABG with left internal thoracic artery being constructed to his left anterior descending artery. Two hours after surgery, complete atrioventricular block developed with circulatory collapse. Emergency cardiac catheterization showed multiple coronary artery spasms and LITA graft spasm, which were refractory to intracoronary and intragraft nitroglycerin injection. So we established IABP and continuous hemofiltration (CHF) urgently. Thereafter, his hemodynamics gradually improved and spasm did not recur. His postoperative angiogram revealed no significant narrowing in coronary arteries and patent anastomosis. IABP and CHF might be one of useful procedure for refractory postoperative coronary spasm. PMID- 11761892 TI - [Double switch operation (Senning and Rastelli operation) with left atrial augumentation by in situ autologous pericardium: a case report]. AB - A 23-month-old female infant with situs solitus, atrioventricular and ventriculoarterial discordance, pulmonary atresia, ventricular septal defect, who had received modfied right Blalock-Taussig shunt (4 mm Gore-Tex tube) at the age of 2 months, was carried out double switch operation with left atrial augumentation by in situ autologous pericardium. The spatial position of the heart was mesocardia. The systemic right ventricular end-diastolic volume was 100% of normal, and the pulmonic left ventricular end-diastolic volume was 105% of normal. Atrioventricular valvular regurgitation was not found. Postoperative course was uneventful. On the 28th postoperative day,she discharged from hospital. The disadvantage of double switch operation is difficulty of atrial switch procedure, because most patients have a small atrium due to dextrocardia or mesocardia. For the purpose of atrial augumentation without artificial materials, our modified Senning procedure is useful. But longer follow-up is necessary to determine whether this technique is indeed beneficial. PMID- 11761894 TI - [Efficacy of off-pump coronary artery bypass grafting in patients requiring noncardiac operations]. AB - Off-pump coronary artery bypass grafting was performed for patients with concomitant disease requiring noncardiac operations. Eight patients underwent CABG prior to or at the same time of noncardiac operation: lung cancer (2), gastric cancer (2), arteriosclerotic occlusive disease (2), abdominal aortic aneurysm (1), aorto-iliac occlusive disease (1). Of these, there were 6 patients who underwent off-pump CABG. Two patients underwent conventional CABG with extracorporeal circulation. Off-pump CABG was performed through a median sternotomy and small left thoracotomy. One patient received quadruple grafts, and another one received double, and 4 received single grafting. Simultaneous noncardiac operations were carried out in 3 patients (Y-grafting, femoro-femoral bypass, mediastinal lymphnode biopsy). The other 3 patients underwent subsequent operations (axillo-femoro-popliteal bypass, aorto-femoral bypass, subtotal gastrectomy). However, of the 2 patients with conventional CABG, 1 died of multiple metastasis after lobectomy of lung cancer that might have been affected by the extra-corporeal circulation. Off-pump CABG is efficient in patients with concomitant disease requiring noncardiac operations. PMID- 11761895 TI - [Surgical repair of postinfarction ventricular septal perforation by endocardial patch with infarction exclusion]. AB - We evaluated the surgical results of postinfarction ventricular septal perforation by endocardial patch with infarction exclusion. MATERIALS AND METHODS: We reviewed 8 patients complicating AMI who underwent surgical treatment at our institution from July 1997 to August 2000 (6 males, 2 females, mean age 73.9 +/- 9, range 57-87). The localization of AMI and VSP was anterior in 6 patients, inferior in 2. All patients had coronary angiography preoperatively. And 7 patients had the percutaneous transluminal coronary angioplasty of the infarct artery. RESULTS: There were 2 hospital deaths due to cerebral infarction and pulmonary hemorrhage. All deaths occurred in patients with cardiogenic shock. CONCLUSION: Good results were obtained by infarction exclusion technique. Better operative results may be expected with the preoperative coronary angioplasty of the infarct artery. PMID- 11761896 TI - [Emergent surgical treatment of type A acute aortic dissection in an elderly patient]. AB - An 86-year-old man with severe chest pain and shock was transferred to our hospital. Computed tomography revealed type A aortic dissection with cardiac tamponade. He needed intubation and closed chest massage preoperatively. At operation, intrapericardial space was filled with clotted blood and rupture of the ascending aorta was confirmed. He underwent a successful emergency graft replacement of the ascending aorta. Postoperative course was uneventful except for mild hemianopsia due to cerebral infarction. He had recovered to be able to walk and is doing well. PMID- 11761897 TI - [Right ventricular outflow tract reconstruction using a three-valved extracardiac conduit of expanded polytetrafluoroethylene vessel graft in the Ross operation: a pediatric case report]. AB - A 16-year-old boy was diagnosed as having severe aortic regurgitation and moderate aortic stenosis due to congenital aortic bicuspid valve. A chest X-ray film showed the cardiothoracic ratio (CTR) of 64% and echocardiography revealed severe dilation of the left ventricular dimension with severe wall thickness. An electrocardiogram showed multiple ventricular arrhythmias. The patient underwent the Ross operation with the reconstruction between the right ventricle and the pulmonary arteries using a three-valved conduit which was made by an expanded polytetrafuloroethylene vessel graft. Ventricular arrhythmia disappeared just after the operation and left ventricular dimensions improved with the CTR of 53% except mild regurgitation of the neo-aortic valve three months later. PMID- 11761898 TI - [Case of thoracoabdominal aortic aneurysm complicated with Buerger's disease]. AB - We report a rare case of 65-year-old man who developed thoracoabdominal aortic aneurysm of Crawford type III complicated with Buerger's disease. He was admitted to our hospital with chief complaints of upper abdominal and back pain. CT showed that the aneurysm extended from the descending thoracic aorta to the aortic bifurcation and its had a maximum width of 95 mm. Angiogram (IA-DSA) revealed that both popliteal arteries were occluded slightly above the level of the knee joint, although collateral vessels were visualized. He underwent preliminary graft replacement of the abdominal aorta with the end-to-side supplemental branch for cannulation. Subsequently we performed graft replacement of the thoracoabdominal aorta with reconstruction of the celiac and superior mesenteric arteries and intercostal arteries on under partial cardiopulmonary bypass. This supplemental branch of abdominal aortic graft was useful in preventing ipsilateral leg ischemia. During the reconstruction of the major visceral branches, the branches were perfused selectively via partial extracorporeal circulation. Post operative courses were uneventful without paraplegia and leg ischemia. Angiographic examination revealed excellent hemodynamic results. PMID- 11761899 TI - [Video-assisted thoracoscopical surgery for pericardial cyst: report of two cases]. AB - Two cases of pericardial cyst are reported. Case 1: A 51-year-old man, was admitted to the hospital because of an abnormal shadow on a chest CT scan. We confirmed a cystic mediastinal tumor situated between the superior vena cava and azygos vein. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. Patient 2, a 34-year-old woman was admitted to the hospital because of an abnormal shadow on a chest radiographic film. Chest CT scan showed a cystic mediastinal tumor. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. We would recommend video-assisted thoracoscopic surgery which is of great value in the treatment of pericardial cyst. PMID- 11761900 TI - [A case of pyoderma gangrenosum after mitral valve replacement]. AB - A 48-year-old male with treated hypothyroidism underwent mechanical valve replacement for mitral valve regurgitation. After the operation, the patient developed progressive median chest wound ulceration. The wound did not heal with conventional therapies for mediastinitis such as administration of antibiotics, debridement of necrotic tissue or continuous irrigation. The entire surgical wound opened spontaneously. Bacterial cultures yielded negative and the wound biopsy specimen revealed non-specific inflammatory change. The anti-TSH receptor antigen level was high. Pyoderma gangrenosum based on auto-immune deficiency was diagnosed and high dose corticosteroid therapy was started. The wound healed completely in 5 months. PMID- 11761901 TI - [Combined off-pump CABG (OPCAB) and abdominal vascular surgery]. AB - Two simultaneous operations for off-pump CABG (OPCAB) and abdominal vascular surgery were performed safely and effectively. [Case 1] A 52-year-old man was admitted with the right intermittent claudication and angina pectoris. Coronary angiography and aortography showed 90% stenosis of left anterior descending coronary artery (LAD) and the right external iliac artery. The patient underwent 1 CABG using left internal thoracic artery (ITA) without cardiopulmonary bypass and abdominal aorta--the right external iliac bypass simultaneously. Bleeding volume during the operation was only 150 ml. The operation time was 3 hours 50 minutes. [Case 2] A 57-year-old man was referred from the other hospital with complaints of abdominal aortic aneurysm. He had the history of 4 stroke attacks caused by idiopathic aldosteronism. Preoperative coronary angiography and aortography showed severe 3 vessels disease and abdominal aortic aneurysm. First, we harvested bilateral ITAs, the right gastroepiploic artery (GEA) and saphenous vein (SV). The complete revascularization (left ITA-LAD, right ITA-1st diagonal branch, GEA-seg. 4 posterodescending branch, SV graft-posterolateral branch) was performed on the beating heart. Then we repaired the abdominal aortic aneurysm (56 mm in diameter) using a Gelsealed Y-graft. The operative course was uneventful. The operation time was 6 hours 15 minutes. These cases suggested that OPCAB technique combined with abdominal vascular surgery reduced operation time and prevented complication in the patient with the risk of brain trouble. PMID- 11761902 TI - [A case of carcinosarcoma of the lung]. AB - A 63-year-old man was admitted to our hospital because of cough and slight fever up. A tumor shadow in right S6 and obstructive pneumonia was detected by X-ray and CT. Bronchoscopic study showed that right B6 bronchous was occluded by the tumor and in which malignant cell (squamous cell carcinoma suspect) were detected. Therefore right middle and lower lobectomy was performed. Histological examination of the resected specimen showed that the tumor was composed of poorly differentiated squamous cell carcinoma and abnormal spindle cell component. Both components of the tumor were mixed each other in part. Immunohistologically, malignant cell of sarcomatous elements were positively stained by vimentin and actine, but was not found such as osteosarcoma or rabdomyosarcoma. He was diagnosed as so-called carcinosarcoma of the lung. PMID- 11761903 TI - [Tension pneumothorax after simultaneous bilateral lung resection]. AB - A 72-year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray film. Chest CT showed a mass 6 cm in diameter in left S1 + 2, and a small round mass in right S2. Left side mass was diagnosed squamous cell carcinoma by transbronchial biopsy, but right side mass was unidentified. We performed partial resection for a right S2 mass with VATS, and then left upper lobe lobectomy and mediastinal lymph node dissection simultaneously. Pathological examination revealed the right mass was hamartoma. He discharged on 16 postoperative days uneventfully. But 3 days after he was sent to our hospital on emergency because dyspnea and unconscious. Chest X-ray revealed right side tension pneumothorax, then he was recovered by chest tube insertion. At re thoracotomy we confirmed air leakage was occurred from a ruptured bulla that was leaved at first operation. PMID- 11761904 TI - [Two surgical cases of pulmonary dirofilariasis]. AB - Two surgical cases of pulmonary dilofilariasis (women aged 80 and 54 years old) were reported. They, who had no history of keeping dogs, were admitted to our hospital with complaining of cough and coin lesion on chest X-ray. On investigation, it was difficult to distinguish between pulmonary dilofilariasis and lung cancer. Wedge resection was performed by video-assisted thoracic surgery (VATS), and a definite diagnosis of pulmonary dilofilariasis was made. Nodes 2-3 cm in diameter are formed beneath the pleura in many cases of pulmonary dilofilariasis. Therefore, VATS is useful owing to its minimal invasiveness. PMID- 11761905 TI - [Pulmonary embolism following lung resection: a case report and review of the Japanese literature]. AB - A 73-year-old male was admitted to our hospital with an abnormal shadow on a chest X-ray film. Chest CT demonstrated that a tumor shadow measuring 23 x 22 mm in size with pleural retraction was located in the right lower lobe. Transbronchial lung biopsy yielded a diagnosis of primary pulmonary adenocarcinoma. We performed a right lower lobectomy with mediastinal lymph node dissection. The patient suddenly complained of a syncope attack, tachycardia, hypotension, and hypoxemia 2 days after surgery. A perfusion lung scintigram with Tc-99 m macroaggregated albumin demonstrated localized defects at both the left lower lobe and a part of the left upper lobe. Thrombolytic and anticoagulation therapy with urokinase and heparin were immediately started. A postoperative lung scintigram 14 days after the onset of pulmonary thromboembolism showed normal filling of the left lung. The patient was discharged on the 37th postoperative day, and he has been followed up with anticoagulation therapy. PMID- 11761906 TI - [A case of thymoma with pure red cell aplasia]. AB - A 71-year-old man was admitted to the hospital because of general fatigue. There were few reticulocytes in the peripheral blood and no erythroblasts in the bone marrow. Chest CT revealed an anterior mediastinal tumor. Under a diagnosis of thymoma with PRCA, extended thymothymectomy was performed. Histological diagnosis was mixed type thymoma with no invasive growth beyond the capsule. Administration of predonisolone following surgery was not effective for PRCA. Otherwise, peripheral blood counts were significantly improved following occasional onset of acute bronchitis. PMID- 11761907 TI - [Non-Alzheimer type dementia in elderly: senile dementia of the neurofibrillary tangle type(SD-NET)]. PMID- 11761909 TI - [Comparison between Dyck's criteria and the polyneuropathy index-revised (PNI-R) in the electrophysiologic evaluation of diabetic neuropathy]. AB - In Rochester diabetic neuropathy research by Dyck et al., abnormal value in two or more nerves was introduced into the nerve conduction criteria of diabetic neuropathy. Polyneuropathy index-revised(PNI-R) is calculated as the mean percentage of the normal of 8 parameters on the motor nerve conduction studies. They were motor nerve conduction velocities in the forearm or leg segment and F wave latencies after wrist or ankle stimulation concerning to the median, ulnar, peroneal and posterior tibial nerves. F-wave latencies were adjusted to 160 cm height and used reciprocals in comparison with normal values. To compare these two indices, first we obtained the normal limit(1st or 99th percentile value) of each parameter from the data of 62 healthy individuals. Then in 78 patients with diabetes mellitus number of abnormal nerves and the PNI-R were investigated. Abnormal values were frequently observed in the categories of motor nerve conduction velocities and F-wave latencies. Amplitude of compound muscle action potential (CMAP) or sensory nerve action potential(SNAP) in each nerve had a large standard deviation. In such parameters abnormal rate was extremely low, because the lower limit of normal being very small. Nevertheless, sigma CMAP which means the summation of amplitudes of 3 CMAPs had as high as 53% of abnormal rate. The coefficient of correlation between number of abnormal nerves and the value of PNI-R mounted up to -0.87. Instead, the coefficient of correlation of sigma CMAP or sigma SNAP, which means the summation of amplitudes of ulnar and sural SNAPs, with PNI-R were 0.65 and 0.79, respectively. In 14 patients PNI-R was normal and the number of abnormal nerves was 0 or 1. In 59 both categories were abnormal, and only in 5 they were not coincide. As to the clinical signs PNI R had better correlation than number of abnormal nerves with vibration threshold or degree of Achilles tendon reflex. sigma CMAP is a convenient index to detect the existence and the degree of neuropathy. This index expresses the degree of neurogenic muscular atrophy, though it doesn't always advance parallel to the decrease in number of motor nerves. sigma SNAP had higher coefficient of correlation with PNI-R or number of abnormal nerves than sigma CMAP. In conclusion, abnormal PNI-R and abnormal value in two or more nerves are both useful and coincide with each other in the detection of diabetic neuropathy. The PNI-R is an excellent quantitative index, and the PNI-R corresponds well with the number of abnormal nerves. These observations indicate that the number of nerves with abnormal value is also available as a simple and semi-quantitative index of diabetic neuropathy. PMID- 11761908 TI - [Disturbance of micturition in Parkinson's disease]. PMID- 11761910 TI - [Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction]. AB - Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However, some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction(midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious(distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen(57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongata in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particulary medulla oblongata infarction. PMID- 11761911 TI - [Diffusion-weighted imaging of brain death: study of apparent diffusion coefficient]. AB - DWI(Diffusion-weighted images) of the brain has been revealed to be useful in diagnosis of several clinical conditions. However, little is known about DWI with regard to brain death. We had opportunities to study patients with brain death. Case 1. A 34-year-old woman experienced cardiopulmonary arrest due to severe ventricular fibrillation, and resuscitated after about 120 minutes. After brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC(apparent diffusion coefficient) values were 30-40% lower than those of normal volunteers. Case 2. A 45-year-old woman experienced cardiopulmonary arrest due to pontine hemorrhage, and was resuscitated after about 20 minutes. Before brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC values were the same as those of normal volunteers. After brain death, DWI showed more clearly defined in these areas, but ADC values were 30-40% lower than the first values. DWI and ADC mapping shows areas corresponding to edema of a cytotoxic nature and to ischemic tissue. The characteristic views of high signals in the whole area of the brain were present, and an objective evaluation was possible with DWI after the brain death diagnosis by measuring ADC values. PMID- 11761912 TI - [A case of Hirayama's disease successfully treated by anterior cervical decompression and fusion]. AB - The authors report the case of a 16-year-old boy with Hirayama's disease(juvenile muscular atrophy of unilateral upper extremity). The present history began about 6 months previously, when he noticed slowly progressive weakness with atrophy of the left hand and forearm. Neurological examination on admission revealed diffuse distribution of muscular atrophy including the left hypothenar, thenar, forearm, and triceps muscles. However, EMG studies identified neurogenic changes in both upper extremities. There was no long tract sign of objective sensory impairment. Plain spinal radiograms showed abnormal kyphosis of the cervical vertebrae. Cervical MR images in the neutral position demonstrated focal atrophy of the cervical cord at the C 5-6 vertebral levels. When the neck was flexed, the cervical cord was displaced anteriorly and was compressed over the posterior surface of the C 5-6 vertebral bodies. He was diagnosed to have Hirayama's disease(cervical flexion myelopathy). Via an anterior approach, he underwent a C 5 vertebrectomy followed by fixation of C 4-6 vertebral bodies using iliac bone and plate system. He recovered from surgery without any complications and has been well for the past 6 months with remarkable improvement of muscle strength. Application of cervical collar for 3 to 4 years has been generally advocated for the treatment of Hirayama's disease because progression of signs and symptoms is usually expected to cease within several years. However, some patients were reported not to response to conservative treatment for more than 5 years after their onsets. To these patients surgery seems to be beneficial, because it can give rise to permanent stable fixation with much shorter period of external cervical immobilization compared with cervical collar therapy, in which long-term application is frequently unbearable in many patients. In conclusion, the present case emphasizes the importance of surgical treatment in Hirayama's disease not only to improve neurological deficits but regain better quality of life. PMID- 11761913 TI - [Treatment of symptomatic convexity arachnoid cyst in the elderly by neuroendoscope assisted-stereotactic surgery: a case report]. AB - A 70-year-old female had Gerstman syndrome and a mild right side hemiparesis. She had no history of head injury. MRI revealed a large left convexity arachnoid cyst. Stereotactic cyst-ventricular shunting assisted by neuroendoscope was performed under local anesthesia. The postoperative course was uneventful. CT scan, performed one week after operation, showed a size reduction of the cyst. Her preoperative clinical signs progressively improved. Symptomatic arachnoid cyst in the elderly is rare. This paper discussed their findings in the previous published papers and the effectiveness of neuroendoscope assisted stereotactic fenestration of the cyst. PMID- 11761914 TI - [Twin-twin transfusion syndrome and intraventricular hemorrhage followed by hydrocephalus: report of two cases]. AB - We report 2 infants who were born as one of monochorial twins. Both of them had been suffering from twin-twin transfusion syndrome(TTTS) as a donor fetus. Case 1 was delivered by caesarean section at the 28th week of pregnancy. On day 0, intraventricular hemorrhage(IVH) occurred from the right subependymal germinal matrix layer, and progressive ventricular enlargement was followed. Case 2 was delivered by the caesarean section at the 31st week of pregnancy. On day 9, he developed IVH from the choroid plexus at the trigone of the left lateral ventricle, and progressive enlargement of the inferior and posterior horns, trigone and posterior part of the body of the left lateral ventricle was followed. IVH in patients with TTTS usually occur in recipient infant but it can also occur in donor infant as in our cases. Pathophysiology of central nervous system damages associated with TTTS is variable and complicated. PMID- 11761915 TI - [A case with diffuse vasospasm after perimesencephalic nonaneurysmal subarachnoid hemorrhage]. AB - Perimesencephalic nonaneurysmal subarachnoid hemorrhage(PNSH), defined as bleeding in the cisterns around the midbrain with a negative four-vessel angiographic study, is uniformly associated with an excellent outcome without associated rebleeding or symptomatic vasospasm. Angiographic vasospasm is uncommon in patients with this disease, and if vasospasm is present, severe and diffuse angiographical vasospasm is rare. We report a case with PNSH who developed severe and diffuse angiographic vasospasm. The patient was a 52-year old woman who suffered an acute severe headache. We diagnosed PNSH from CT and angiographical findings, and treated her conservatively. Serial angiography, that was performed on the fourteenth day after hemorrhage, showed diffuse and severe angiographic vasospasm affecting both the anterior and the posterior circulation. She was treated with normovolemia, and remained no neurological symptom. Follow up MR angiography showed improvement of the angiographic vasospasm. When the presence of diffuse and severe vasospasm is detected, a diagnosis of PNSH should not be excluded. PMID- 11761916 TI - [Acute edematous encephalopathy presenting with refractory generalized status epilepticus: an autopsy case]. AB - A previously healthy, 29-year-old man developed generalized convulsion with disturbed consciousness 3 days after the flu-like symptoms. On the next day, his convulsion evolved into generalized status epilepticus (GSE) that was unresponsive to administration of various anticonvulsants. Then, intravenous anesthetic agents, including midazolam, propofol and vecuronium sodium, were continuously infused. During the following 9 days, despite of high-dose infusion of these anesthetic agents, his GSE could not be suppressed, and complex partial seizure with secondary generalization frequently occurred. The patient was comatose and mechanically ventilated, whereas the brainstem reflexes were preserved. Electroencephalogram revealed a diffuse slowing of the background activity and occasional focal spike and wave complexes with secondary generalization. Cerebrospinal fluid analysis showed pleocytosis and elevated protein concentration. Cranial CT scans obtained on day 8 demonstrated brain edema. On day 10, his GSE ceased with abolition of the brainstem reflexes, and he lapsed into brain death resulting from the progressive brain edema. Over the following six days, his systemic circulation gradually worsened, and he died on day 16. On postmortem examination, the brain was markedly edematous and showed the findings consistent with acute anoxic encephalopathy with extensive circulatory stasis. Mild gliosis was observed in the insular cortex, yet no evidence of inflammatory disease was found throughout the brain. This patient was characterized by acutely progressive severe brain edema without inflammatory changes, suggesting that his primary disease was acute toxic encephalopathy presumably induced by viral infection. His GSE was refractory and unresponsive to the intensive treatment with the intravenous anesthetic agents. This case epitomizes the difficulties in controlling refractory seizures in some patients with encephalopathy or encephalitis. PMID- 11761917 TI - [A pediatric case of intractable complex partial seizures associated with mesial temporal lobe astrocytoma: usefulness of interictal epileptiform discharges in the present case]. AB - The patient was a 10-year-old male with normal developmental milestones. He had medically intractable complex partial seizures since the age of 7 years. At the age of 10 years, he had focal motor seizures of the right face, and a head CT scan showed a calcified lesion in the left mesial temporal region. The tumor exhibited low intensity on T 1-weighted and high intensity on T 2-weighted MR images, and was not enhanced by gadolinium-diethylenetriamine pentaacetic acid. Interictal SPECT showed hypoperfusion in the left temporal region. One-day video/EEG monitoring revealed very frequent epileptiform discharges which occurred only during sleep period exclusively in the left anterior-to-middle temporal region. The patient underwent lesionectomy with the guidance of electrocorticography. The histological study of the resected tissue showed astrocytoma. After surgery he has had no seizures for 10 months. It was concluded that very frequent interictal epileptiform discharges strictly localized to the temporal lobe at which MRI-identified tumor was present could be predictive of epileptogenic zone in the present patient in whom clinical symptoms and the results of other studies were also concordant. PMID- 11761918 TI - [Subacute combined degeneration with liner high intensity lesion of columns on MRI]. PMID- 11761919 TI - [Oculomotor nerve palsy caused by the abscess of the clivus]. PMID- 11761920 TI - [A 64-year-old man with parkinsonism as an initial symptom followed by dementia associated with marked abnormal behaviours]. AB - We report a 64-year-old man with parkinsonism as an initial symptom, which was followed by dementia and abnormal behaviours. He was well until 1985, when he was 49 years old, when he noted rest tremor in his right hand. Soon tremor appeared in his left hand as well. He was seen in our clinic and levodopa was prescribed. He was doing well with this medication, however, in 1993, he started to suffer from on-off phenomenon. He also noted visual hallucination. In 1994, he stole a watermelon and ate it in the shop. He repeated such abnormal behaviours. In 1995, he was admitted to the neurology service of Hatsuishi Hospital. On admission, he was alert and oriented. He did not seem to be demented; however, he admitted stealing and hypersexual behaviours. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, downward gaze was markedly restricted. He showed masked and seborrhoic face, and small voice. No motor palsy was noted, but he walked in small steps with freezing and start hesitation. Marked neck and axial rigidity was noted. Tremor was absent except for in the tongue. No cerebellar ataxia was noted. Deep tendon reflexes were diminished. Plantar response was extensor bilaterally. Forced grasp was noted also bilaterally. He was treated with levodopa and pergolide, but he continued to show on-off phenomenon. His balance problem and akinesia became progressively worse; still he showed hypersexual behaviour problems. He also showed progressive decline in cognitive functions. In 1997, he started to show dysphagia. He developed aspiration pneumonia in July of 1998. In 1999, he developed emotional incontinence and became unable to walk. He also developed repeated aspiration pneumonia. He died on March 1, 2000. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had corticobasal degeneration. Other diagnoses entertained included dementia with Lewy bodies, diffuse Lewy body disease, and frontotemporal dementia. Majority of the participants thought that diffuse Lewy body disease was most likely. Post-mortem examination revealed marked nigral neuronal loss, gliosis and Lewy bodies in the remaining neurons. Abundant Lewy bodies of cortical type were seen wide spread in the cortical areas, but particularly many in the amygdaloid nucleus. Lewy bodies were also seen in the subcortical structures such as the dorsal motor nucleus, oculomotor nucleus, Meynert nucleus, putamen, and thalamus. What was interesting was marked neuronal loss of the pontine nuclei, demyelination of the pontocerebellar fiber, and moderate neuronal loss of the cerebellar Purkinje neurons, a reminiscent of pontocerebellar atrophy. However, the inferior olivary nucleus was intact. PMID- 11761921 TI - [Liver tumor escape from immune surveillance]. PMID- 11761922 TI - [Telomere and hepatocarcinogenesis]. PMID- 11761923 TI - [Hepatocarcinogenesis and genomic instability]. PMID- 11761924 TI - [Oncogene c-myc]. PMID- 11761925 TI - [A novel tumor suppressor gene, TSLC1]. PMID- 11761926 TI - [Tumor suppressor gene IGF2 receptor]. PMID- 11761927 TI - [Loss of heterozygosity in hepatocarcinogenesis]. PMID- 11761928 TI - [Global epidemiology of hepatocellular carcinoma]. PMID- 11761929 TI - [Tumor suppressor RB gene and its related molecules in hepatocellular carcinoma]. PMID- 11761930 TI - [Tumor suppressor gene, p53, and hepatocarcinogenesis]. PMID- 11761931 TI - [DNA methylation]. PMID- 11761932 TI - [Abnormality of cyclin D1 gene]. PMID- 11761933 TI - [Angiogenesis related factors: angiopoietin-2]. PMID- 11761934 TI - [Alterations of mismatch repair gene in hepatocellular carcinoma]. PMID- 11761936 TI - [Recent progress in study of mechanism of invasion and metastasis of hepatocellular carcinoma]. PMID- 11761935 TI - [beta-catenin]. PMID- 11761937 TI - [Matrix metalloproteinase (MMP), matrix serine proteinase (MSP), tissue inhibitor of metalloproteinase (TIMP)]. PMID- 11761938 TI - [Syndecan-1]. PMID- 11761939 TI - [VEGF]. PMID- 11761940 TI - [E-cadherin]. PMID- 11761941 TI - [Natural course of hepatocellular carcinoma]. PMID- 11761943 TI - [Premalignant lesions of hepatocellular carcinoma]. PMID- 11761942 TI - [Histological classification of hepatocellular carcinoma]. PMID- 11761944 TI - [Classification of degree of liver damage and cancer stage]. PMID- 11761945 TI - [High risk group and screening methods of hepatocellular carcinoma]. PMID- 11761946 TI - [Imaging diagnosis of hepatocellular carcinoma]. PMID- 11761947 TI - [Early diagnosis of hepatocellular carcinoma using ultrasonography]. PMID- 11761948 TI - [Is US angiography (USAG) still a gold-standard in the diagnosis of hepatocellular carcinoma]. PMID- 11761949 TI - [Descriptive epidemiology of intrahepatic cholangiocarcinoma]. PMID- 11761950 TI - [Diagnostic usefulness of color Doppler US to hepatocellular carcinoma]. PMID- 11761951 TI - [FFT analysis of blood flow in hepatocellular carcinoma]. PMID- 11761952 TI - [Three dimensional ultrasound diagnosis of hepatocellular carcinoma]. PMID- 11761953 TI - [Dynamic CT, helical CT]. PMID- 11761954 TI - [Angio CT]. PMID- 11761955 TI - [Three-dimensional computed tomography (CTA, CTAP)]. PMID- 11761957 TI - [Xenon-enhanced CT]. PMID- 11761956 TI - [MDCT]. PMID- 11761958 TI - [The recent progress of MRI]. PMID- 11761959 TI - [Dynamic MRI]. PMID- 11761960 TI - [3D-MR angiography(MRA)]. PMID- 11761961 TI - [Nuclear medicine(FDG-PET)]. PMID- 11761962 TI - [Hepatic angiography]. PMID- 11761963 TI - [Intravenous ultrasound contrast agent, Levovist]. PMID- 11761964 TI - [Ultrasound contrast imaging with next generation contrast agents]. PMID- 11761965 TI - [Super para magnetic iron oxide--Feridex]. PMID- 11761966 TI - [Hepatocyte targeted MR contrast agent--Gd-BOPTA(E-7155)]. PMID- 11761967 TI - [MR contrast agent: resovist (SH U 555A)]. PMID- 11761968 TI - [Pathological diagnosis of hepatocellular carcinoma]. PMID- 11761969 TI - [Alpha-fetoprotein and its fucosylation index in the early diagnosis of hepatocellular carcinoma]. PMID- 11761970 TI - [PIVKA-II high-sensitivity PIVKA-II]. PMID- 11761971 TI - [Trends in research of hepatocarcinogenesis]. PMID- 11761972 TI - [Clinical significance of p53 antibody]. PMID- 11761973 TI - [High risk group for development of hepatocellular carcinoma]. PMID- 11761974 TI - [Prognostic factors in patients with hepatocellular carcinoma]. PMID- 11761975 TI - [p53 mutations as prognostic factors of hepatocellular carcinomas]. PMID- 11761976 TI - [AFP mRNA in the circulation]. PMID- 11761977 TI - [Cell proliferating activity and cell cycle-associated proteins]. PMID- 11761978 TI - [Hepatocellular carcinoma]. PMID- 11761979 TI - [Cholangiocellular carcinoma (intrahepatic bile duct carcinoma)]. PMID- 11761980 TI - [Multistep carcinogenesis of HCC]. PMID- 11761981 TI - [Combined hepatocellular carcinoma and cholangiocellular carcinoma]. PMID- 11761982 TI - [Fibrolamellar carcinoma]. PMID- 11761983 TI - [Early hepatocellular carcinoma]. PMID- 11761984 TI - [Advanced hepatocellular carcinoma]. PMID- 11761985 TI - [Multiple hepatocellular carcinoma]. PMID- 11761986 TI - [Hepatocellular carcinoma in patients who has survived more than 10 years without recurrence after surgery]. PMID- 11761987 TI - [Metastatic liver tumor]. PMID- 11761988 TI - [Features of hepatitis B virus-related hepatocellular carcinoma]. PMID- 11761989 TI - [Hepatitis C virus-related hepatocellular carcinoma]. PMID- 11761990 TI - [Hepatocellular carcinoma without hepatitis virus markers]. PMID- 11761991 TI - [Hypercarcinogenic state]. PMID- 11761992 TI - [Hepatocellular carcinoma associated with alcoholic liver diseases]. PMID- 11761993 TI - [Hepatocellular carcinoma complicating autoimmune hepatitis]. PMID- 11761994 TI - [Hepatocellular carcinoma accompanied with primary biliary cirrhosis]. PMID- 11761995 TI - [Hepatocellular carcinoma in patients with metabolic liver disease]. PMID- 11761996 TI - [Hepatocellular carcinoma in patients with parasitic liver disease--Japanese schistosomiasis and hepatocellular carcinoma]. PMID- 11761997 TI - [Hepatocellular carcinoma complicating Budd-Chiari syndrome]. PMID- 11761998 TI - [Hepatocellular carcinoma without underlying liver disease]. PMID- 11761999 TI - [Treatment for hepatocellular carcinoma]. PMID- 11762000 TI - [Overview of percutaneous ablation therapy]. PMID- 11762001 TI - [Mechanisms of hepatocarcinogenesis by hepatitis B virus(HBV) infection]. PMID- 11762002 TI - [Surgical resection for hepatocellular carcinoma]. PMID- 11762003 TI - [Surgical treatment for small hepatocellular carcinoma]. PMID- 11762004 TI - [Liver resection for advanced hepatocellular carcinoma]. PMID- 11762005 TI - [Transcatheter arterial embolization/chemoembolization]. PMID- 11762006 TI - [Transcatheter arterial chemoembolization using autologous blood clot for the treatment of hepatocellular carcinoma: long-term results of treatment and prognostic factors]. PMID- 11762007 TI - [A new embolic material: SAP-microsphere]. PMID- 11762008 TI - [A new embolic agent--DSM(degradable starch microsphere)]. PMID- 11762009 TI - [Percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma]. PMID- 11762010 TI - [Hepatocarcinogenesis by HCV infection]. PMID- 11762011 TI - [Percutaneous hot ethanol injection therapy (PHEIT)]. PMID- 11762012 TI - [Ethanol mixtured with lipiodol regional injection therapy]. PMID- 11762013 TI - [Percutaneous hepatic infarction therapy (PIT)]. PMID- 11762014 TI - [Percutaneous acetic acid injection therapy]. PMID- 11762015 TI - [Percutaneous microwave coagulation therapy (PMCT)]. PMID- 11762017 TI - [Radiofrequency ablation for liver tumors]. PMID- 11762016 TI - [Laparoscopic and thoracoscopic microwave coagulation for hepatocellular carcinoma]. PMID- 11762018 TI - [Laparoscopic radiofrequency ablation for hepatocellular carcinomas]. PMID- 11762019 TI - [Transgenic mouse as a model for viral hepatocarcinogenesis]. PMID- 11762020 TI - [Laser induced thermotherapy for hepatocellular carcinoma]. PMID- 11762021 TI - [Management of complications associated with local ablation therapy for hepatocellular carcinoma]. PMID- 11762022 TI - [Hepatic arterial infusion chemotherapy (anthracycline)]. PMID- 11762023 TI - [Hepatic arterial infusion chemotherapy using 'low dose FP']. PMID- 11762024 TI - [Hepatic arterial infusion chemotherapy for hepatocellular carcinoma by EEP regimen]. PMID- 11762025 TI - [Arterial infusion chemotherapy with SMANCS]. PMID- 11762026 TI - [Examination of in vitro chemosensitivity test using methylthiazole tetrazolium bromide chemosensitivity (MTT) test with combined drugs in hepatic arterial infusion chemotherapy for carcinoma of the liver]. PMID- 11762027 TI - [Adverse reaction of hepatic arterial infusion chemotherapy for hepatocellular carcinoma]. PMID- 11762028 TI - [Chemotherapy for hepatocellular carcinoma]. PMID- 11762029 TI - [Hyperthermia for hepatocellular carcinoma]. PMID- 11762030 TI - [Radiotherapy of hepatocellular carcinoma]. PMID- 11762031 TI - [Efficacy of proton irradiation for HCC]. PMID- 11762032 TI - [Genetic control of hepatocarcinogenesis in mice]. PMID- 11762033 TI - [Charged particle (carbon-ion) therapy]. PMID- 11762034 TI - [DDP-H, new formulation of cisplatin for hepatic artery infusion therapy]. PMID- 11762035 TI - [Somatostatin analogue (octreotide)]. PMID- 11762036 TI - [Angiogenesis inhibitor (TNP-470: AGM-1470)]. PMID- 11762037 TI - [Immunotherapy]. PMID- 11762038 TI - [Immune therapy against hepatocellular carcinoma using gene-modified tumor cells]. PMID- 11762039 TI - [Immunotherapy for hepatocellular carcinoma using dendritic cells]. PMID- 11762040 TI - [Gene therapy for hepatocellular carcinoma]. PMID- 11762041 TI - [Epidemiology of hepatocellular carcinoma in Japanese population]. PMID- 11762042 TI - [Liver transplantation for hepatocellular carcinoma]. PMID- 11762043 TI - [Role of alcohol and free radical in hepatocarcinogenesis]. PMID- 11762044 TI - [Multimodal therapy including hepatectomy for multiple hepatocellular carcinomas]. PMID- 11762045 TI - [Transcatheter arterial embolization therapy and local ablation]. PMID- 11762046 TI - [Combination of PMCT and PEIT for treatment of hepatocellular carcinoma]. PMID- 11762047 TI - [Balloon-occluded radiofrequency ablation for patients with hepatocellular carcinoma]. PMID- 11762048 TI - [Transcatheter local hyperthermia]. PMID- 11762049 TI - [Radiation therapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma]. PMID- 11762050 TI - [Hepatic arterial infusion chemotherapy combined with interferon-alpha for hepatocellular carcinoma]. PMID- 11762051 TI - [Prevention of hepatocellular carcinogenesis by interferon]. PMID- 11762052 TI - [Hepatocarcinogenesis with chemicals including mycotoxins]. PMID- 11762053 TI - [Retinoid]. PMID- 11762054 TI - [Prevention of development of hepatocellular carcinoma from HCV-associated liver cirrhosis by multi-agents therapy including stronger-neo-minophagen C]. PMID- 11762055 TI - [Sho-saiko-to]. PMID- 11762056 TI - [Present status and problems of hepatocellular carcinoma detected by ultrasonographic screening]. PMID- 11762057 TI - [Mass screening for high risk group of hepatocellular carcinoma]. PMID- 11762058 TI - [Cost-benefit of ultrasonographic mass screening for hepatocellular carcinoma]. PMID- 11762059 TI - [Quality of life in the treatment of hepatocellular carcinoma]. PMID- 11762060 TI - [Treatment for hepatocellular carcinoma under consideration of quality of life]. PMID- 11762061 TI - [Informed consent of treatment for HCC]. PMID- 11762062 TI - [Informed consent for high risk group of hepatocellular carcinoma]. PMID- 11762063 TI - [Hyperplastic foci and multicentric hepato-carcinogenesis]. PMID- 11762065 TI - [Hepatocellular carcinogenesis and Helicobacter hepaticus infection]. PMID- 11762064 TI - [Tumor dormancy therapy for hepatocellular carcinoma]. PMID- 11762066 TI - [The effects of radiation exposure on human hepatocarcinogenesis]. PMID- 11762067 TI - [Hepatoma-derived growth factor (HDGF) and HDGF family]. PMID- 11762068 TI - [Development of hepatocellular carcinoma during chronic hepatitis]. PMID- 11762069 TI - [Escape from apoptosis in liver cancer cells]. PMID- 11762070 TI - ["Cell eats itself" autophagy as a transport system from the cytoplasm to lysosomes]. PMID- 11762071 TI - [The late endosome as a molecular sorting station]. PMID- 11762072 TI - [Function of lysosomal membrane glycoproteins]. PMID- 11762073 TI - [Functions of acidic compartments in mammalian system]. PMID- 11762074 TI - [Vacuole: gigantic plant organelle with lysosomal function]. PMID- 11762075 TI - [Molecular strategy for parasitism and vaccine development of falciparum malaria]. PMID- 11762076 TI - [Molecular mechanism of stop codon recognition by eRF1: a wobble hypothesis for peptide anticodons]. PMID- 11762078 TI - [Knowing similarity in protein 3D structure]. PMID- 11762077 TI - [Intra-and extra-thymic development of NKT cells]. PMID- 11762079 TI - [Percutaneous pigtail catheter drainage of peripheral breast abscesses]. AB - Almost all peripheral non-lactational breast abscesses are staphylococcal in origin and so percutaneous drainage can be a valid alternative to surgical incision. Percutaneous drainage was performed in eight patients with one or more abscesses. A pigtail catheter was inserted only in foci greater than 3 cm. The results were good in 9 out of 10 purulent collections; one recurrence was observed in the smallest focus. All patients but one underwent local anesthesia and were managed as outpatients. PMID- 11762080 TI - [Evaluation of seminal and hormonal parameters in idiopathic varicocele before and after surgical intervention]. AB - 268 patients (age 16-47 years) affected with idiopathic varicocele, submitted to surgery, have been studied. Semen analysis, pampiniphorm plexus doppler examination and testosterone, estradiol, D4 androstenedione, DHEA-S, HPRL, 17-OH P, FSH and LH (basal and after LH-RH) evaluation, before and 6 months after surgery, were performed. The patients were divided in 3 groups (A, B and C) according to sperm count. Pre-surgery seminal parameters in A group were significantly reduced in comparison with control group. Six months after surgery, a significant increase of total and forward progression, Swelling test, Acridine Orange and in vitro penetration (CMPT) was observed. Sperm count showed an increase, although being still significantly reduced in comparison with normal controls. In B group, before surgery, sperm count, viability, Acridine Orange and CMPT were significantly reduced in comparison with controls. Six months after surgery, viability, Acridine Orange and CMPT resulted significantly improved. In C group, before surgery, CMPT resulted significantly reduced in comparison with controls. After surgery, semen framework improved without significant differences in comparison with normal controls. No significant differences were observed for hormonal patterns before and after surgery. PMID- 11762081 TI - [Spontaneous rupture of the esophagus]. AB - A series of 8 patients with spontaneous rupture of the esophagus is analysed. Correct diagnosis is difficult. The time lapse between the rupture and diagnosis nevertheless seems to be the most important single factor in the outlook for treatment of spontaneous rupture of the esophagus. Early primary closure of the tear and good drainage of the mediastinum and pleural cavity give the best results in such cases. Sometimes a conservative management should be advocated for the treatment of esophageal perforations. PMID- 11762082 TI - [Abdominal compartment syndrome in video laparoscopic surgery. Etiopathogenetic aspects, physiopathology and personal experience]. AB - The abdominal compartment syndrome (ACS) is a very seven pathology, consequence oh abdominal injuries and traumatism, acute pancreatitis, aortic aneurism rupture, acute peritonitis. The etiopatogenesis is the increase of intra abdominal pressure with systemic consequences for cardiorespiratory and renal failure. The authors after careful physiopathologic consideration, describe, a case report of ACS in the laparoscopic cholecystectomy for acute cholecystitis. To conclusion, we report very important the accurate intraoperative monitoring of vital parameters (PCO2, PO2, Pa, Fc, PVC, Ph, Diuresis) and immediate decision at laparotomic conversion for abdominal decompression. PMID- 11762083 TI - [Digestive hemorrhage in portal hypertension: role of sclerotherapy]. AB - Haemorrhage is perhaps the most terrible complication of portal hypertension whatever is the etiopathology. The authors point out how sclerotherapy of the varices is either a prophylaxis and a therapeutic procedure with a low rate of local and systemic complications. Even if they are supported by good results in personal experience, the authors notice as important is to tailor the treatment for each patient. PMID- 11762084 TI - [Informatics in a surgery department]. AB - In this paper the Authors describe their own experience in applying informatics at the Surgical Division III of Azienda Policlinico Universitario of Messina. After a discussion about existing hardware (LAN of PC) and daily used software (commercial suite) for managing the clinical reports and correlated data (images, medical prescription, reservations, and so on), their conclusion is that a great development on this way will be possible with extension of the services to all the business network and then to WAN as Internet. PMID- 11762085 TI - [Simultaneous and bilateral catheterization of inferior petrosal sinuses in the diagnosis of Cushing's syndrome: basal multiple sampling and after ACTH-releasing hormone test]. AB - In 22 patients with ACTH-dependent Cushing's syndrome we have performed multiple ACTH evaluations, baseline and after ACTH-releasing hormone (CRH), during simultaneous bilateral inferior petrosal sinus sampling. The basal inferior petrosal sinus/periphery ratio for ACTH was > 2 in 11/22 patients, CRH challenge caused the appearance of an inferior petrosal sinus/periphery ratio > 3 in 6 other patients. An ACTH-secreting adenoma was surgically proven in 17 patients with ACTH inferior petrosal sinus/periphery ratio > 2 basally or > 3 after CRH and in 1 patient with an inferior petrosal sinus/periphery ratio < 2 basally or 3 after CRH. In 4 patients the very high peripheral ACTH levels, the inferior petrosal sinus/periphery ratio and the lack of ACTH increase after CRH indicated the presence of an ectopic ACTH syndrome. An ACTH intersinus gradient > 1.4 was found in 11 patients. Among these patients the adenoma was correctly localised in 6 and wrongly in 5 patients. In conclusion, the diagnostic accuracy of the inferior petrosal sinus sampling was of 95.4% (21/22 cases) considering basal and CRH-stimulated ACTH levels. The multiple basal ACTH evaluation does not seem to be necessary associated with CRH-test, but may be helpful in some cases. PMID- 11762087 TI - A little skepticism. Physicians wonder about impact of workers' comp reform. PMID- 11762086 TI - A two-front war. PMID- 11762088 TI - Diabetes on a rampage. PMID- 11762089 TI - No more on-time delivery. PMID- 11762090 TI - The often overlooked posterior dislocation of the shoulder. AB - Unlike most shoulder dislocations, the posterior dislocation is truly a diagnostic challenge to the treating physician because it may be missed more often than it is recognized. In fact, more than 60% of posterior dislocations are misdiagnosed initially by the treating orthopedic surgeon, and the correct diagnosis is often delayed for months or years. A history of seizures, electroshock, or a fall onto a flexed, adducted arm should alert the physician to the possibility of posterior dislocation. A careful physical examination with comparison to the unaffected arm must be performed with particular attention given to subtle posterior fullness and anterior flatness of the shoulder, along with a lack of external rotation and abduction. A radiographic trauma series made in the scapular plane must always be obtained in cases of shoulder trauma to rule out posterior dislocation. A computed tomographic scan may also be necessary. The correct diagnosis of this injury will facilitate proper orthopedic evaluation and treatment and will reduce the incidence of missed posterior shoulder dislocation and its associated morbidity. PMID- 11762091 TI - Maybe AMA should be more like TMA. PMID- 11762092 TI - Evaluation of systematic reviews of treatment or prevention interventions. PMID- 11762093 TI - The making of a new medical school. PMID- 11762094 TI - Decontamination of reusable surgical instruments. PMID- 11762095 TI - Cochlear and middle ear implants: advances for the hearing impaired. AB - We have entered into an era of surgical audiology with cochlear and middle ear implants. With both devices there are distinct phases of patient management- patient selection, surgery, programming and rehabilitation. These phases and issues relating to the implants themselves are considered in this article. PMID- 11762096 TI - The case for a one-stop balance centre. AB - Vertigo, imbalance and dizziness are poorly understood symptoms. This lack of understanding often results in a feeling of therapeutic impotence and frustration. Despair may be felt by the treating physician and hence the patient. This is particularly unfortunate because most patients with imbalance can be helped, often on a single-visit basis. PMID- 11762097 TI - Current trends in managing chronic middle ear disease. AB - Major advances in reconstruction continue to be made in the treatment of chronic middle ear disease, while little prophylaxis is available and indications for intervention remain in many cases controversial. This reflects our lack of knowledge of the true causes of these diseases. PMID- 11762098 TI - An update on Dupuytren's contracture. AB - The standard treatment of Dupuytren's contracture of the digits, to date, is surgical. The aetiology, pathology, clinical findings and present day treatment are discussed and possible treatment for the future is suggested. PMID- 11762099 TI - Linezolid: a new antibiotic for gram-positive infections. AB - Linezolid is a new antibiotic that can treat multiresistant gram-positive infections and can be given parenterally or by mouth. It is not related to any existing agent so cross resistance is unusual. PMID- 11762100 TI - Modern management of migraine. AB - Migraine presents with episodic disabling headache, with additional features that distinguish it from other headache syndromes: it is not 'just a headache'. Treatment must be carefully selected, titrated and adjusted according to individual patient response. PMID- 11762101 TI - Managing urinary incontinence in the elderly. AB - Urinary incontinence is a common and unpleasant problem for older people. Age related changes to the urinary tract, age-related diseases and medications, as well as the underlying bladder problem that contributes to urinary incontinence, should be identified for successful management. PMID- 11762102 TI - Haematuria: a streamlined approach to management. AB - Haematuria can often herald significant underlying pathology. This article highlights the potential causes of haematuria and suggests a management algorithm. PMID- 11762103 TI - Informed consent and the preregistration house officer. AB - A survey of preregistration house officers demonstrated that less than a third had never felt compelled to obtain consent from patients for procedures they themselves did not understand. This had occurred frequently for over a fifth of respondents. Learning how to obtain informed consent is an important part of the education and training of a doctor. The wrong lessons will be learned if they feel compelled to do this when ill-equipped with relevant information about risks and alternatives. PMID- 11762104 TI - Publishing on the Internet: why bother? AB - This article outlines the rationale for the author who is thinking of publishing material directly via the Internet rather than through the established channels of publishing houses and peer-reviewed journals. PMID- 11762105 TI - Two cases of parotid gland swelling in patients taking clozapine. PMID- 11762106 TI - Acute abdomen following cardiac catheterization: a surprising outcome. PMID- 11762107 TI - Laparoscopically assisted splenectomy for idiopathic thrombocytopenic purpura in a previously conserved spleen. PMID- 11762109 TI - Violence on psychiatrists. PMID- 11762108 TI - Violence on psychiatrists. PMID- 11762110 TI - The new Mental Health Act. PMID- 11762111 TI - The implications of herbal medicines for anaesthesia. PMID- 11762112 TI - Are you really working harder now? PMID- 11762113 TI - How humiliating simply to fall apart! PMID- 11762114 TI - Dispense the drugs you prescribe? PMID- 11762115 TI - A celebration that couldn't wait. PMID- 11762116 TI - Does mandated diabetes coverage boost compliance? PMID- 11762117 TI - Treating pain: damned if you don't? PMID- 11762118 TI - Why I'm going to stay where I'm needed. PMID- 11762119 TI - A department head's liability for a colleague's mishap. PMID- 11762120 TI - Professor Oleh Hornykiewicz on the occasion of his 75th birthday and the first L DOPA treatment of Parkinson's disease 40 years ago. PMID- 11762121 TI - How L-DOPA was discovered as a drug for Parkinson's disease 40 years ago. PMID- 11762122 TI - [Is there a need for new clinical-ethical models in medical research?]. PMID- 11762123 TI - [Practice guidelines for formulation of patient or subject information and for the declaration of consent in genetic studies (inclusive of pharmaceutical genetics]. PMID- 11762124 TI - Increased intracranial arterial resistance in patients with type 2 diabetes mellitus. AB - BACKGROUND: The majority of the studies investigating risk factors for stroke have focused on the atherosclerosis of extracranial carotid arteries. Risk factors for the involvement of intracranial arteries in patients with stroke have not been widely investigated so far. The pulsatility index reflects the vascular resistance of intracranial arteries and could therefore be used as an estimate of the severity of vascular damage. MAIN PURPOSE: The present study aimed to examine the influence of type 2 diabetes mellitus and some other atherosclerosis risk factors on intracranial vascular resistance in patients with a previous stroke or transient ischemic attack. METHODS: Transcranial doppler investigations were performed in 103 patients with previous stroke (31 with diagnosis of type 2 diabetes, 72 without diabetes), at least 3 months after stroke occurred. Blood flow velocities of anterior cerebral arteries, middle cerebral arteries, the intracranial part of vertebral arteries and the basilar artery, as well as of the extracranial part of the internal carotid artery were measured, and Gosling's pulsatility index was calculated. The maximal pulsatility index of intracranial arteries was defined to express the most pronounced damage. RESULTS: Diabetic patients had a significantly higher pulsatility index than non-diabetic patients in all examined intracranial arteries. The maximal pulsatility index was also significantly higher in diabetic patients than in non-diabetic patients (1.24 +/- 0.25 vs. 1.00 +/- 0.23; p < 0.0001). There was no significant difference in the pulsatility index between men and women and between groups of patients with or without hypertension. In the multivariate analysis, the presence of diabetes (p < 0.0001) and the age of patients (p < 0.0001) were the only factors significantly predicting maximal pulsatility index, and this relationship was independent on the presence of hypertension. CONCLUSIONS: Diabetic patients with previous stroke have a higher pulsatility index than non-diabetic patients with previous strokes, which indicates a higher increase in intracranial arterial resistance and more severe damage to cerebral blood flow in diabetes mellitus. PMID- 11762125 TI - Prescription of analgesics in general medical practice. AB - The aim of this study was to examine the frequency of prescription of analgesic drugs by General Practitioners in Austria, the reasons for which they are prescribed, as well as relevant organizational details. A questionnaire was designed to prospectively collect data from 14 participating General Practitioners over a period of at least 20 days each. The type of analgesic drugs prescribed during direct (doctor) or indirect (receptionist) consultations was recorded, coded according to the ATC classification and separated into first and repeat consultations. Furthermore, the diagnostic terms and the individual intensity of pain perception by the patients were noted. During 7248 consultations recorded, 1083 prescriptions of analgesics were issued. The majority of first prescriptions are issued during direct consultations, whereas a large number of repeat prescriptions are prepared for the doctor's supervision by the receptionists via indirect consultations. Almost half of the patients receive repeat prescriptions. In both, direct and indirect consultations with patients, approximately every 7th contact results in the prescription of an analgesic drug. The antirheumatic drug group is the most frequently prescribed group of painkillers whereas opioids are rarely prescribed. Selection of drugs is not clearly related to the degree of pain experienced by individual patients. Problems of the musculo-skeletal system rank first among the classifications leading to prescription of an analgesic. Pain needs quick and efficient therapy. Prescriptions of analgesics in General Practice ought to be issued in such a way as to serve this large group of patients without, however, taking extensive risks: repeat and first prescriptions issued during indirect consultations have to be precisely recorded and need the doctor's personal supervision. PMID- 11762126 TI - Intraductal papillary-mucinous tumors of the pancreas: presentation of eight cases. AB - BACKGROUND AND STUDY AIMS: The mucinsecreting intraductal papillary-mucinous tumors of the pancreas are a rare entity with characteristic duodenoscopic and radiological features. These tumors have a broad spectrum of presentation. The diagnosis requires highly experienced and attentive endoscopists. Once diagnosed, resection of the tumor is recommended to prevent progression to malignancy. This surgical procedure has a low acceptance, mainly in the elderly patients. Therefore, a "wait and see" strategy may be necessary in those patients refusing operation. PATIENTS AND METHODS: Between 1996 and 2000, intraductal papillary mucinous tumors of the pancreas were diagnosed in eight patients (5 females, 3 males) using endoscopic retrograde cholangiopancreatography, and confirmed by brush cytology and/or histology and analyzed retrospectively. RESULTS: The patients showed typical endoscopic and radiological findings: dilatation and mucin extrusion of the papillary orifice, easy passage of instruments into the dilated main pancreatic duct, which showed patchy filling defects after application of contrast medium. Patients were informed about the diagnosis in detail. Two patients were inoperable. Surgery was recommended to the other six patients. Two of the six patients agreed to surgical treatment. The remaining four patients were included in a follow-up protocol. These patients were observed for up to 5 years. Only one patient showed minor progression of ERCP-findings. CONCLUSION: Intraductal papillary-mucinous tumors of the pancreas can be well characterized by means of endoscopy and radiology. Poor compliance to surgical treatment makes individual multidisciplinary management and follow-up necessary. PMID- 11762127 TI - 1902-2002: a hundred years later. Moriz Kaposi 1837-1902: a historical reappraisal. PMID- 11762128 TI - Research advances in ethanol metabolism. AB - The pharmacokinetics of alcohol determines the time course of alcohol concentration in blood after the ingestion of an alcoholic beverage and the degree of exposure of organs to its effects. The interplay between the kinetics of absorption, distribution and elimination is thus important in determining the pharmacodynamic responses to alcohol. There is a large degree of variability in alcohol absorption, distribution and metabolism, as a result of both genetic and environmental factors. The between-individual variation in alcohol metabolic rates is, in part due to allelic variants of the genes encoding the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). This review summarizes recent developments in the investigation of the following influences on alcohol elimination rate: gender, body composition and lean body mass, liver volume, food and food composition, ethnicity, and genetic polymorphisms in alcohol metabolizing enzymes as well as in the promoter regions of the genes for these enzymes. Evaluation of the factors regulating the rates of alcohol and acetaldehyde metabolism, both genetic and environmental, will help not only to explain the risk for development of alcoholism, but also the risk for development of alcohol-related organ damage and developmental problems. PMID- 11762129 TI - [Alcohol and nutrition]. AB - Alcoholism and alcohol-associated organ injury is one of the major health problems worldwide. Alcohol may lead to an alteration in intermediary metabolism and the relation between alcohol intake and body weight is a paradox. The effect of alcohol intake on resting metabolic rate, assessed by indirect calorimetry, and lipid oxidation, is still controversial. Small quantities of ethanol seem to have no effect on body weight. Ingestion of moderate amounts may lead to an increase in body weight, via a lipid-oxidizing suppressive effect. Chronic intake of excessive amounts in alcoholics leads to a decrease in body weight, probably via increased lipid oxidation and energy expenditure. Chronic ethanol abuse alters lipid-soluble (vitamins A, D and E) and water-soluble (B-complex vitamins, vitamin C) vitamins status, and some trace elements status such as magnesium, selenium or zinc. PMID- 11762130 TI - [Alcohol and oxidative stress]. AB - There is accumulating evidence pointing oxidative stress as a mechanism of ethanol toxicity. Oxidative stress takes place when the balance between the antioxidant defenses and the generation of reactive oxygen species (ROS) is tipped in favour of the latter. Ethanol metabolism is directly involved in the production of ROS, but ethanol also participated to the formation of an environment favourable to oxidative stress such as hypoxia, endotoxemia and cytokine release. Following ethanol intoxication, balance between prooxidants and antioxidants is disturbed to such an extent that it results in an oxidative damage of biomolecules. The ability of ethanol to induce peroxidation of membrane lipids is widely reviewed in literature. More recently it has also been described that ethanol can oxidize proteins and ADN. In this review, is also discussed the impairment of cellular function resulting from this situation of oxidative stress. PMID- 11762131 TI - [Alcohol-xenobiotic interactions. Role of cytochrome P450 2E1]. AB - Alcohol and xenobiotics share the same oxidative microsomal pathway, which is mainly located in the endoplasmic reticulum of hepatocytes. This pathway involves enzymes that belong to the super family of cytochrome P450 and allows to explain a lot of pharmacokinetic or toxic interactions between alcohol and xenobiotics. Cytochrome P450 2E1 (CYP2E1) is the key enzyme of the microsomal pathway of ethanol oxidation. It is inducible by chronic ethanol consumption and its activity is increased by three to five fold in liver from alcoholics subjects. This induction involves to a lesser extent cytochromes P450 3A4 and 1A2 and contributes to the metabolic tolerance of alcohol and drugs observed in alcoholics. The metabolic tolerance persits several days after ethanol withdrawal. Furthermore, CYP2E1 has a high capacity to activate numerous xenobiotics into toxic or carcinogenic compounds. Drugs currently used such as paracetamol, anesthetics (enflurane, halothane), industrial solvents (benzene or its derivatives), halogenated solvents (CCl4, trichlorethylene) and nitrosamines which are present in food or tobacco smoke are included. Therefore, heavy consumption of alcohol, which results in CYP2E1 induction, increases individual susceptibility to the toxic or carcinogenic effects of these xenobiotics. PMID- 11762132 TI - Genetic polymorphisms of alcohol metabolizing enzymes. AB - Alcohol metabolism is one of the biological determinants that can significantly influence drinking behavior and the development of alcoholism and alcohol-induced organ damage. Most ethanol elimination occurs by oxidation to acetaldehyde and acetate, catalyzed principally by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Other ethanol oxidation pathways, including catalase and microsomal ethanol-oxidizing system (MEOS/CYP2E1), as well as the nonoxidative pathway (FAEES), which forms fatty acid ethyl esters, appear to play a minor role. The major alcohol metabolizing enzymes exhibit genetic polymorphism and ethnic variation. In this review recent advances in the understanding of the functional polymorphisms of ADH, ALDH and CYP2E1 and their metabolic, physiologic and clinical correlations are presented. PMID- 11762133 TI - The genetics of addiction: alcohol-dependence and D3 dopamine receptor gene. AB - Alcohol-dependence is a complex phenotype, with behavioral, psychological, pharmacological, medical and social dimensions. Aggregation studies, adoption and twin researches have demonstrated that the vulnerability to alcohol-dependence is at least in part linked to genetic factors, the genetic vulnerability to alcoholism being mainly not substance-specific. There are numerous candidate genes, but the D3 dopamine receptor is specifically located in the limbic area, and in particular in the nucleus accumbens, which are involved in reward and reinforcement behavior. Furthermore, a previous collaborative study showed that homozygosity for the Ball DRD3 locus was more frequently observed in opiate dependent patients with high sensation seeking scores. In this study, we analyzed the distribution of Ball DRD3 polymorphism in a new sample of 131 French male alcoholic-patients (DSM III-R criteria) and 68 healthy controls matched for sex and origins. Although we replicated the higher sensation seeking score in alcohol dependent patients with comorbid dependence, we found no significant difference in the DRD3 gene polymorphism between controls and alcoholic patients, regardless of sensation seeking score, addictive or psychiatric comorbidity, alcoholism typology, and clinical specificities of alcoholism. There is good evidence that gene coding for the dopamine receptor D3 does not play a major role in the genetic vulnerability to alcoholism. PMID- 11762134 TI - [Applications of magnetic resonance spectrometry (MRS) in the study of metabolic disturbances affecting the brain in alcoholism]. AB - The purpose of this article is to provide an overview of the current applications of magnetic resonance spectroscopy (MRS) to the investigation of cerebral metabolism in alcoholic patients. The specific metabolic changes associated with the intoxication process (tolerance, dependance), abstinence and alcohol-related diseases (alcoholic encephalopathy, cirrhosis, Gayet-Wernicke's encephalopathy, Marchiafava-Bignami syndrome) are described. PMID- 11762135 TI - [Alcohol, chronobiology and sleep]. AB - Chronobiology is the scientific discipline of biologic rhythm study. Applications of the emerging concepts of chronobiology are now use in several fields of clinical medicine. Alcohol related disorders seems to be clarified with the main concepts of chronobiology. Thus chronopharmacology (specially chronokinetics and time-related differences in drug effects) clears up variations of blood alcohol levels and toxicity of ethanol during the 24 h, chronesthesy explains the action of ethanol on biological rhythms of hormone secretions and sleep, and the concept of chronopathology seems to be apply to alcohol dependence. We review in this article some applications in alcohol related disorders of the main concepts of chronobiology. PMID- 11762136 TI - [Fetal alcohol syndrome: nervous system damage and clinical phenotype]. AB - Alcohol is much more slowly eliminated in the fetus than in the mother (< 50%). The ethanol and its derivative the acetaldehyde have a constant dose-effect on the development of the nervous system central. The individual susceptibility to alchol teratogenic effect in utero is responsible of variable clinical phenotype. This teratogenicity is constant during all the development of the central nervous system. The diagnosis of fetal alcohol syndrome (FAS) associates three criteria: delay of pre- and postnatal growth, abnormal development of the central nervous system, craniofacial abnormalities. Cerebral malformations are extremely variable, being to relate to the various stages of development of the nervous system central. Neurochimic abnormalities interest mainly the mono-aminergic system. The backwardness is the best known consequence of SAF (34 to 851%). It is not constant. Facial dysmorphic results of joint abnormalities whose none is pathognomonic but whose grouping is evocative. Psychomotor instability is the most frequent expression on the behavioral phenotype. PMID- 11762137 TI - Alcoholic liver injury: pathogenesis and therapy in 2001. AB - Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and promising prospects for even more effective treatments. It continues to be important to replenish nutritional deficiencies when present but it is crucial to recognize that, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to SAMe but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for administration of the products of the reaction. It might also be beneficial to add other compounds to such therapeutic regiment. Since free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise. Several have been investigated experimentally and PPC is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Anti-inflammatory agents are also required. In addition to down regulators of cytokines and end toxic are being considered. Finally, since excess drinking is the crux of the issue, anticraving agents should be incorporated in any contemplated therapeutic cocktail, in view of the recent promising results obtained with some of these agents such as naltrexone and acamprosate. PMID- 11762138 TI - [Alcohol and pancreas]. AB - The mechanism of the pancreatic toxicity of alcohol is not completely elucidated. Many cofactors may contribute to the pancreatic toxicity of alcohol: diet, genetic factors. Chronic pancreatitis occurs after a long lasting and heavy alcoholism. During the first years, acute manifestations occur and, then endocrine and exocrine pancreatic insufficiency. PMID- 11762139 TI - [Alcohol and cancer]. AB - Regular consumption of alcoholic beverages increases the risk of cancer in the upper aero-digestive tract and in the liver. There is a dose-response relationship and the effects are combined with those of tobacco, according to a multiplicative model. The biologic mechanisms are unclear. Prevention is theoretically possible, but the risks concern levels of consumption generally considered as safe. PMID- 11762140 TI - [Alcohol and cardiovascular system: mechanisms of the protective effects]. AB - Moderate and regularly alcohol consumption reduces death rate from coronary heart disease and thrombotic stroke. This beneficial correlation observed with several alcoholic beverages seems to be mainly due to an ethanol effect. However the particular role of microconstituants contained in red wine must be considered. The mechanism of the putative protective effect of alcohol intake is mediated through the elevation of HDL cholesterol and through the aintioxydative effect of polyphenolic compounds. In addition, alcohol acts favourably on platelets agregation, fibrinolysis and several other coagulation parameters. Despite these explanations are yet speculative and there is no causal relation between alcohol and reduced coronary death, epidemiological data are consistent with the belief that daily consumption of one or two glasses of an alcoholic beverage has salutary effect on health. PMID- 11762141 TI - [Moderate alcohol consumption and cardiovascular diseases]. AB - While excessive ethanol consumption can result in higher rate of morbidity and mortality resulting from several diseases including cancer and cirrhosis, epidemiological studies suggest that moderate alcohol ingestion reduces the risk of cardiovascular diseases. However, the precise mechanisms by which moderate alcohol consumption protects against coronary heart disease (CHD) is not fully understood. Epidemiological studies suggest that alcohol consumption influences several risk factors for CHD including blood pressure, plasma cholesterol levels, platelet function, and fibrinolytic parameters, preventing both vascular thrombosis and occlusion. Turning to molecular and cellular levels, ethanol has been shown to act on several signal transduction mechanisms involve in the inhibition of smooth muscle cells proliferation and migration and in the activation of the release of vasoactive factors from vascular cells such as nitric oxide (NO). The latter is of importance since NO has been shown to possess antioxidant, antiaggregant properties, to regulate vascular tone and to inhibit both proliferation of smooth muscle cells and adhesion of leukocytes. Altogether, the above mentioned beneficial properties of moderate concentration of ethanol might help to explain the cardio- and vascular protection induced by ethanol. This review compels several bibliographic data concerning the cardiovascular effect of moderate alcohol consumption. PMID- 11762142 TI - [Peripheral markers, future perspectives]. AB - Four of the recently described peripheral markers of alcohol abuse have been reviewed. The acetaldehyde adducts allow to detect an alcohol abuse lasting for several weeks, even after a recent alcohol withdrawal. Inversely, 5 hydroxytryptophol (5-HTOL) reflects the alcohol consumption of the last 24 hours. Its detection is possible after the blood alcohol concentration has disappeared. Its measurement is run in urine samples, thus without invasive sampling. The hyaluronic acid and the activity of beta-hexosaminidase are markers of hepatobiliary alcohol induced disorders more than direct markers of alcohol intake. Acetaldehyde adducts could be used as markers of long term alcohol abuse, CDT as a marker of the recent alcohol abuse, and 5-HTOL the detection of alcohol abuse of the past day. PMID- 11762143 TI - Mechanisms of twinning. IV. Sex preference and lactation. AB - OBJECTIVE: To examine the likelihood of twinning through conception during lactation and to attempt to explain why there is an increased sex ratio with monozygotic twinning. STUDY DESIGN: Parturients who had become pregnant while still breastfeeding were asked to supply information about their gestations. Also, records from two maternity services over a three-year period were examined for the sex of monozygotic twin sets. Zygosity was confirmed with the pathology reports of the placentas. RESULTS: Much like that in a previously published study, the sex ratio (females/total) was found to be 0.60 in monozygotic twins. In the case of lactating gravidas, the incidence of twinning was much higher than in a random population (11.4% versus 1.1%). CONCLUSION: These findings are consistent with the model of twinning as a consequence of a depressed calcium environment and its effect on embryonic intercellular bonding. PMID- 11762144 TI - Intralesional injection for hepatic metastasis from cervical carcinoma. A report of two cases. AB - BACKGROUND: The treatment of isolated hepatic metastasis from carcinoma of the uterine cervix has yet to be established. We tested the efficacy of percutaneous injection of ethanol and acetic acid as a curative-intent treatment modality for this rare event. CASES: Under real-time sonographic guidance, two patients with a solitary hepatic metastasis from carcinoma of the cervix were treated with 99.5% percutaneous ethanol injection (one patient) and 50% percutaneous acetic acid injection (the other patient). The treatment was repeated weekly if laboratory data permitted and aspiration cytology interpreted on site showed tumor cells. Cytology after complete treatment showed no residual tumor cells in either case. Both patients had no evidence of disease during follow-up for 12 and 24 months, respectively. CONCLUSION: Treatment was successful in two patients with isolated hepatic metastatic lesions from carcinoma of the cervix who received percutaneous injection of 99.5% ethanol or 50% acetic acid. PMID- 11762145 TI - Forceps delivery after molar malignancy in a woman with arteriovenous malformation. A case report. AB - BACKGROUND: An arteriovenous (AV) fistula in the female pelvis is a rare finding. This report describes a successful pregnancy after selective embolization of a postmolar vascular malformation. CASE: At 5 weeks of pregnancy, a 27-year-old, white female, gravida 3, para 0, was discovered on ultrasound examination to have an AV malformation along with a fetal pole. The patient was asymptomatic and had previously received two courses of chemotherapy for a previous nonmetastasized malignant molar pregnancy. Doppler ultrasonography uncovered a vascular malformation extending from the margin of the fetal pole to the margin of the uterus. The pregnancy ended at 8 weeks with a spontaneous abortion. The patient underwent angiography and embolization of extensive right-sided uterine vessels. She resumed normal menstrual periods six weeks after the embolization and became pregnant. The pregnancy concluded in low forceps vaginal delivery of a healthy, female infant at 34 weeks. CONCLUSION: Vaginal delivery following postmolar pregnancy and a uterine AV malformation may be considered a viable delivery option. PMID- 11762146 TI - Accidental vaginal incision during cesarean section. A report of four cases. AB - BACKGROUND: Transverse vaginal incision during cesarean section, also known as anterior vaginotomy, is a recognized entity, mostly made unintentionally. CASES: At our institution, four patients underwent a transverse vaginal incision during cesarean section over an eight-year period. In three of them, excessive bleeding required blood transfusion. In one case, only hypogastric artery ligation resulted in bleeding control. None of the patients had subsequent vaginal deliveries. CONCLUSION: The exact incidence of anterior vaginotomy is difficult to evaluate. Accidental vaginal incision occurs mostly following a prolonged second stage of labor but is possible during the first stage. Risk factors include prolonged second stage of labor and an emergency setup. Reported complications resulting from anterior vaginotomy include excessive hemorrhage, with a possible need for hysterectomy, difficult approximation, and bladder or ureter injury. Massive bleeding and multiple blood transfusions occurred in our series as well. Fetal outcome and future obstetric behavior do not seem to be compromised. A high index of suspicion is essential when trying to avoid accidental anterior vaginotomy. Meticulous hemostasis, a search for bladder injury and anatomic closure are mandatory when managing this complication. PMID- 11762147 TI - Pancreaticoduodenectomy as treatment of adenocarcinoma of the papilla of Vater diagnosed during pregnancy. A case report. AB - BACKGROUND: Papillary adenocarcinomas are rare tumors of the gastrointestinal tract. There are few reports of this neoplasm diagnosed during pregnancy. CASE: A case of adenocarcinoma of the papilla of Vater was diagnosed by sonographically guided biopsy during pregnancy. The patient underwent radical resection of the tumor at 25 weeks' gestation; pregnancy termination was not indicated. At 39 weeks' gestation, a cesarean-section was performed. The postoperative period entailed total parenteral nutrition until intestinal motility stabilized. This ensured the mother and fetus' well-being until delivery. CONCLUSION: Papillary adenocarcinoma is associated with good prognosis since it is totally removed by radical resection, and pancreaticoduodenectomy can be performed successfully during pregnancy, but the patient must receive special prenatal care. PMID- 11762148 TI - Obstetrician-gynecologists' views on the health risks of obesity. AB - OBJECTIVE: To assess the knowledge and opinions of obstetrician-gynecologists concerning the health risks of obesity and the importance of weight management of patients to clinical practice. STUDY DESIGN: A questionnaire survey covering physician and patient demography, disease risk related to obesity, relevance of weight management to patient's health, and self-assessments of medical education and training was sent to the 418 American College of Obstetricians and Gynecologists (ACOG) fellows who constitute the Collaborative Ambulatory Research Network and to 700 ACOG fellows selected at random. RESULTS: Five hundred twenty five surveys were returned (47.0% response rate). Membership in the network was not a significant factor regarding responses; therefore, the data were pooled. Respondents estimated that 20.6 +/- 0.5% of their patients were obese and that a further 35.9 +/- 0.8% were overweight. The respondents were knowledgeable concerning health risks associated with obesity, and a majority considered obesity to be a major health concern that should be treated. Weight management was considered an important or very important part of practice by 81.5% of respondents. Almost half the respondents (45.5%) thought that the importance of weight management would increase. More than one of three responding physicians (36.4%) had prescribed weight loss medications in the previous year. Most responding physicians did not consider medical school or residency to be sources of information on these issues. CONCLUSION: Obstetrician-gynecologists think that managing the weight of their patients is part of their clinical responsibilities but do not consider their training in medical school and residency on these topics to be adequate. PMID- 11762149 TI - Headless spermatozoa in semen specimens from fertile and subfertile men. AB - OBJECTIVE: To investigate the frequency of headless, or unnucleated, spermatozoa, determine its percentage and evaluate its possible correlation with other semen parameters. STUDY DESIGN: Semen specimens from 94 subfertile men, aged 24-53 years (mean +/- SD 33.3 +/- 6.3) and from 52 fertile men, aged 24-44 (33.3 +/- 4.1) were studied. Two semen specimens were examined from each individual, with a six- to eight-week interval. Sperm morphology was evaluated from Papanicolaou stained smears, and the classification of abnormal sperm forms was made according to the guidelines of the World Health Organization. RESULTS: The percentage of headless spermatozoa was 9.0% +/- 8.8 in subfertile and 2.7% +/- 3.1 in fertile men. Headless spermatozoa existed in semen specimens from 90% of subfertile and 70% of fertile men. Of subfertile men, 23.4% had headless spermatozoa at a higher percentage than the highest normal limit found in sperm smears from fertile men. CONCLUSION: In some cases of subfertile men with a high percentage of headless spermatozoa, their infertility can be attributed to the cause of this morphological abnormality. Moreover, tails but not heads were found in semen specimens from subfertile and fertile men. PMID- 11762150 TI - Pyometra. What is its clinical significance? AB - OBJECTIVE: To evaluate the clinical outcomes of pyometra. STUDY DESIGN: Retrospective study conducted between 1993 and 1999 in two regional hospitals. RESULTS: Pyometra represented 0.038% of gynecologic admissions. Of the 27 women with pyometra, 6 (22.2%) cases were associated with malignancy, 1 (3.7%) was associated with genital tract abnormality, and 20 (74.1%) were idiopathic. Patients with idiopathic pyometra tended to be older and had a higher incidence of concurrent medical conditions. Five (18.5%) women experienced spontaneous perforation of pyometra. A preoperative diagnosis was correctly made in 17 of 22 (77.3%) patients without spontaneous perforation. Most women were treated with dilatation of the cervix and drainage. Nine women (33.3%) had persistent or recurrent pyometra; three of them were asymptomatic. CONCLUSION: Pyometra is an uncommon condition, but the incidence of associated malignancy is considerable, and the risk of spontaneous perforation is higher than previously thought. Dilatation and drainage is the treatment of choice, and regular monitoring after initial treatment is warranted to detect persistent and recurrent disease. PMID- 11762151 TI - Penetrating capacity of human spermatozoa cool preserved in electrolyte-free solution. AB - OBJECTIVE: To evaluate whether human spermatozoa preserved in electrolyte-free (EF) solution at 4 degrees C possess normal penetrating capacity. STUDY DESIGN: The acrosomal status of human spermatozoa cool preserved in EF solution was evaluated before preservation and before and after reinitiation by using chlortetracycline staining. The zona-free hamster egg sperm penetration test was performed using spermatozoa cool preserved in EF solution. RESULTS: The percentages of capacitated and acrosome-reacted spermatozoa cool preserved in EF solution before reinitiation were similar to those of fresh spermatozoa, but they significantly increased after reinitiation. The penetration rate and fertility index of spermatozoa cool preserved in EF solution were comparable to those of fresh spermatozoa (48.3% vs. 50.8% and 1.37 +/- 0.15 vs. 1.29 +/- 0.10, respectively). CONCLUSION: Human spermatozoa cool preserved in EF solution for one week can possess as much penetrating capacity as fresh spermatozoa. PMID- 11762152 TI - Effects of oral and transdermal hormone replacement therapy on internal carotid artery pulsatility indices in postmenopausal women. A prospective, randomized, comparative study. AB - OBJECTIVE: To compare the effects of oral and transdermal hormone replacement therapy on the internal carotid artery pulsatility index in postmenopausal women. STUDY DESIGN: Thirty-seven women were randomized to six months of treatment with oral (n = 19) or transdermal (n = 18) sequential combined hormone replacement therapy. The internal carotid artery pulsatility index was assessed by color Doppler ultrasound at baseline and after six months of treatment. RESULTS: Carotid artery pulsatility indices were significantly lower than the mean of 0.939 +/- 0.139 at 0.860 +/- 0.084 in the oral hormone replacement group and significantly lower than the mean of 0.928 +/- 0.092 at 0.891 +/- 0.046 in the transdermal hormone replacement therapy group (P = .042) after six months of treatment. The mean changes in the carotid artery pulsatility index between the oral and transdermal hormone replacement groups were nonsignificant (-0.078 +/- 0.131 and -0.037 +/- 0.067, respectively; P = .53). There was a significant negative correlation between the change in pulsatility index during treatment and baseline values in the carotid artery (r = -.81, P = .001), but no correlation was found with time since menopause and serum estradiol level. CONCLUSION: Oral and transdermal sequential hormone replacement therapy are similarly effective at six months in reducing impedance to flow in the internal carotid artery. PMID- 11762153 TI - Urinary profile of endogenous steroids in postmenopausal women with stress urinary incontinence. AB - OBJECTIVE: To predict the role of estrogen in prevention of and therapy for stress urinary incontinence by comparing the urinary levels of estrogens and androgens and, to indirectly evaluate metabolism of estrogens and androgens by comparing the concentration ratios of precursor metabolites with those in controls (normal subjects). STUDY DESIGN: Urine samples collected for 24 hours were obtained from postmenopausal women with stress urinary incontinence (n = 20) and from age-matched, postmenopausal, normal female subjects (n = 14). The urinary levels of 20 estrogens and 25 androgens were analyzed by gas chromatography/mass spectrometry. RESULTS: The urinary levels of androgens were significantly higher in patients with stress urinary incontinence than normal subjects, and the urinary levels of estrogens were somewhat higher in patients than normal subjects. However, there were no significant differences between the groups, nor were there significant differences in the metabolism of estrogens and androgens between two groups. CONCLUSION: The urinary levels of endogenous steroids were rather higher in patients with stress urinary incontinence than in normal subjects, so it appears that estrogen should not play a significant role in prevention of and therapy for stress urinary incontinence. PMID- 11762154 TI - Pregnancy prolongation in triplet pregnancies. Oral vs. continuous subcutaneous terbutaline. AB - OBJECTIVE: To assess gestational gain in triplet pregnancies treated with oral terbutaline followed by treatment with continuous subcutaneous terbutaline. STUDY DESIGN: From a database of patients who received perinatal home care services, we identified women with triplet gestations first receiving daily oral terbutaline following an episode of threatened preterm labor who subsequently received continuous subcutaneous terbutaline infusion after recurrence of preterm contractions. The primary outcome studied was gestational gain with oral terbutaline vs. gestational gain with continuous subcutaneous terbutaline infusion. RESULTS: One hundred four women were studied. The mean gestational age at enrollment was 22.0 +/- 2.7 weeks. Significantly more gestational gain was achieved during subcutaneous tocolytic treatment than during oral treatment (mean 5.4 +/- 3.4 vs. 2.8 +/- 2.2 weeks, P < .001). Twenty-nine percent of desired prolongation was achieved with oral terbutaline, while 71% of desired prolongation was achieved with subcutaneous terbutaline infusion (P < .001). The mean gestational age at delivery was 33.2 +/- 2.2 weeks. CONCLUSION: Gestational gain was greater in triplet pregnancies during treatment with continuous subcutaneous terbutaline infusion than with oral terbutaline. PMID- 11762155 TI - Medical vs. Surgical treatment of ectopic pregnancy. The University of New Mexico's six-year experience. AB - OBJECTIVE: To review and compare the treatments for ectopic pregnancy in a university setting serving an indigent population. STUDY DESIGN: Charts assigned an ICD-9 code for ectopic pregnancy from January 1, 1993, through December 31, 1998, were reviewed for presenting symptoms, hCG levels, ultrasound findings, treatment modality and need for subsequent treatment. RESULTS: Of 401 patients treated for ectopic pregnancy, 7 were managed expectantly. One hundred nineteen (30%) patients received methotrexate. Seventy percent (83/119) of these ectopic pregnancies resolved with a single dose and an additional 11 after a second dose, for a 79% overall success rate. Twenty-five patients (21%) failed methotrexate therapy and required surgical treatment, and 11 (9%) pregnancies were ruptured. Primary treatment was surgical in 275 (69%) patients: 172 (63%) underwent laparoscopy and 103 (37%) laparotomy. Primary laparoscopic treatment was successful in 90%. Success rates were significantly lower for medical therapy as compared to laparoscopic treatment (79% vs. 90%, odds ratio 2.2, 95% confidence interval 1.1, 4.3; P = .02). No discriminating predictors of successful treatment with methotrexate were identified. CONCLUSION: The success rate of methotrexate therapy for ectopic pregnancy was lower than that of surgical management in a university setting serving an indigent population. PMID- 11762156 TI - Influenza vaccination during pregnancy. Patients' and physicians' attitudes. AB - OBJECTIVE: To identify potentially remediable attitudinal factors among women and their physicians that may present barriers to influenza vaccination during pregnancy. STUDY DESIGN: We conducted a prospective survey study administered concurrently during influenza season (January-March 2000) to postpartum women in an urban, high-volume medical center and to practicing obstetricians in the metropolitan Los Angeles area. Analyses focused on individual questions' relation to the outcomes of: (1) patients' receipt of influenza vaccine during the recently completed pregnancy, and (2) physicians' discussion of influenza vaccine with their pregnant patients. RESULTS: Surveys were completed by 242 postpartum women and 113 physicians. Among the women, 22% had discussed influenza vaccine with their physicians during pregnancy, with only 8% of respondents having been vaccinated. Significantly more physicians stated that they discussed vaccination with their patients than did women (74% vs. 22%; P < .001). Physicians were more likely to recommend vaccine if they were aware of current Centers for Disease Prevention and Control guidelines (RR = 2.6, 1.1-5.9), gave vaccinations in their offices (RR = 1.2, 1.01-1.4) and had been vaccinated against influenza themselves (RR = 1.9, 1.3-2.8). CONCLUSION: Influenza vaccination during pregnancy occurred infrequently in this study cohort, and a significant discrepancy was seen between patients' and physicians' impressions of whether its use or recommendation had been discussed. Gaps existed in both groups' understanding of potential benefits of influenza vaccine for both pregnant women and their newborns. The survey results suggest potential strategies for targeting improved educational programs for physicians and patients to improve influenza vaccination rates for pregnant women. PMID- 11762157 TI - Mechanisms of twinning. III. Placentation, calcium reduction and modified compaction. AB - OBJECTIVE: To elucidate phenomena contributing to the maintenance and persistence of early uniovular pregnancies. It is proposed that the decreased survival of monozygotic (MZ) multifetal gestations is related to a smaller uteroplacental junctional (UPJ) area during and following implantation when compared with dizygotic (DZ) pregnancies. STUDY DESIGN: Pertinent placental data were collected and analyzed. From this information the placental area was calculated, and an estimate of the size of the UPJ was derived. RESULTS: In the first part of the study, MZ twins, triplets, quadruplets and quintuplets displayed a decrease in mean placental area per neonate as the number of fetuses increased in each set. In the second part, as predicted, MZ twin placentas exhibited smaller placental junctional areas than DZ. This is seen as a direct result of decreased trophectoderm mass due to scission in early gestation. CONCLUSION: These data are consistent with the general impression that multifetal pregnancies, especially monozygotic, are more at risk than singletons because of diminished placental support per fetus. They also reinforce the proposal that the key to MZ twinning is depressed calcium levels. PMID- 11762158 TI - Femtosecond near-infrared lasers as a novel tool for non-invasive real-time high resolution time-lapse imaging of chloroplast division in living bundle sheath cells of Arabidopsis. AB - Non-linear excitation of fluorophores by contemporaneous absorption of two or more near-infrared (NIR) photons following diffraction-limited focusing with high numerical-aperture objectives circumvents out-of-focus fluorescence (without a confocal pinhole) and spatially limits photobleaching and photodamage to the minute sub-femtoliter focal volume. This is in contrast to optical events in conventional confocal imaging systems using ultraviolet (UV) or visible laser sources wherein the entire sectors of the specimen above and below the plane of focus experience massive photostress and photodamage. In addition, NIR wavelengths penetrate deeper into the highly scattering environs of plant tissue than UV and visible wavelengths. We delineate a novel non-invasive technique using NIR femtosecond laser pulses at lambda = 740, 760, 780, and 800 nm for induction of chlorophyll fluorescence by the two-photon effect as well as for intra-tissue time-lapse vital three-dimensional imaging of fundamental events of chloroplast division in deeply seated bundle sheath cells of Arabidopsis thaliana (L.) Heynh. leaves. Our findings establish that (i) mature bundle sheath chloroplasts are indeed capable of division, (ii) the dividing chloroplasts assume a distinct constricted/dumbbell-shaped profile with an average lifespan of 20-25 min, (iii) the complete division of the pre-existing chloroplasts occurs within 50 min, and (iv) the two derivative daughter chloroplasts are invariably unequal in size. This novel NIR-laser-based technique has any number of potential applications, including (i) non-invasive intra-vital imaging of molecular and ion dynamics, (ii) non-destructive screening of mutants impaired in photosynthesis, (iii) diagnosis of physiological states of plants and (iv) bio-optical taxonomy. PMID- 11762159 TI - Tobacco transformants with strongly decreased expression of pyrophosphate:fructose-6-phosphate expression in the base of their young growing leaves contain much higher levels of fructose-2,6-bisphosphate but no major changes in fluxes. AB - The role of pyrophosphate:fructose-6-phosphate 1-phosphotransferase (PFP) in developing leaves was studied using wild-type tobacco (Nicotiana tabacum L.) and transformants with decreased expression of PFP. (i) The leaf base, which is the youngest and most actively growing area of the leaf, had 2.5-fold higher PFP activity than the leaf tip. T3 transformants, with a 56-95% decrease in PFP activity in the leaf base and an 87-97% decrease in PFP activity in the leaf tip, were obtained by selfing and re-selfing individuals from two independent transformant lines. (ii) Other enzyme activities also showed a gradient from the leaf base to the leaf tip. There was a decrease in PFK and an increase in fructose-6-phosphate,2-kinase and plastidic fructose-1, 6-bisphosphatase, whereas cytosolic fructose-1,6-bisphosphatase activity was constant. None of these gradients was altered in the transformants. (iii) Fructose-2,6-bisphosphate (Fru2,6bisP) levels were similar at the base and tip of wild-type leaves in the dark. Illumination lead to a decrease in Fru2,6bisP at the leaf tip and an increase in Fru2,6bisP at the leaf base. Compared to wild-type plants, transformants with decreased expression of PFP had up to 2-fold higher Fru2,6bisP at the leaf tip in the dark, similar levels at the leaf tip in the light, 15-fold higher levels at the leaf base in the dark, and up to 4-fold higher levels at the leaf base in the light. (iv) To investigate metabolic fluxes, leaf discs were supplied with 14CO2 in the light or [14C]glucose in the light or the dark. Discs from the leaf tip had higher rates of photosynthesis than discs from the leaf base, whereas the rate of glucose uptake and metabolism was similar in both tissues. Significantly less label was incorporated into neutral sugars, and more into anionic compounds, cell wall and protein, and amino acids in discs from the leaf base. Metabolism of 14CO2 and [14C]glucose in transformants with low PFP was similar to that in wild-type plants, except that synthesis of neutral sugars from 14CO2 was slightly reduced in discs from the base of the leaf. (v) These results reveal that the role of PFP in the growing cells in the base of the leaf differs from that in mature leaf tissue. The increase in Fru2,6bisP in the light and the high activity of PFP relative to cytosolic fructose-1,6-bisphosphatase in the base of the leaf implicate PFP in the synthesis of sucrose in the light, as well as in glycolysis. The large increase in Fru2,6bisP at the base of the leaf of transformants implies that PFP plays a more important role in metabolism at the leaf base than in mature leaf tissue. Nevertheless, there were no major changes in carbon fluxes, or leaf or plant growth in transformants with below 10% of the wild-type PFP activity at the leaf base, implying that large changes in expression can be compensated by changes in Fru2,6-bisP, even in growing tissues. PMID- 11762160 TI - Purification and properties of an endo-beta-1,4-glucanase from strawberry and down-regulation of the corresponding gene, cel1. AB - An endo-beta-1,4-glucanase (EG) was purified from ripe strawberry (Fragaria x ananassa Duch.) fruit using cellulose affinity chromatography. The purified enzyme gave a single protein band of 54 kDa on sodium dodecyl sulphate polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of this protein showed strong homology with the proteins encoded by recently identified EG genes from different strawberry cultivars and from Arabidopsis, pepper and tomato. The enzyme specifically cleaved the beta-1,4-glucosyl linkages of xyloglucan but was unable to hydrolyze those of insoluble cellulose. The pH optimum and Km of the enzyme against the artificial substrate carboxymethylcellulose (CMC) were pH 5.0-7.0 and 1.3 mg ml-1, respectively. To assess the role of the Cell enzyme in fruit softening a cDNA of the corresponding fruit-specific and ripening-enhanced strawberry gene, cell, was used to down regulate cell gene expression in transgenic strawberry plants. In several primary transformants, cell mRNA was strongly suppressed in ripe fruit. However, the EG activity and firmness of these fruit were indistinguishable from those of control fruit. The expression of a second gene, cel2, encoding a different strawberry EG was unaltered in the fruits of these transformants. The presence of the cel2 transcript in transgenic plants may have prevented the specific down-regulation of cell from revealing its role in fruit softening. PMID- 11762161 TI - Heat stress induces the synthesis of a new form of ribulose-1,5-bisphosphate carboxylase/oxygenase activase in cotton leaves. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) activase mRNA and protein synthesis were measured in the leaves of cotton (Gossypium hirsutum L.) plants under control (28 degrees C) or heat-stress (41 degrees C) conditions. A decline in activase transcript abundance occurred rapidly during the photoperiod and was unaffected by heat stress. In response to high temperature, de novo protein synthesis rapidly shifted from mainly expression of Rubisco large and small subunits to the major heat-shock proteins, while de novo synthesis of the constitutively expressed 47- and 43-kDa activase polypeptides was not appreciably altered. However, heat stress induced the synthesis of a 46 kDa polypeptide that immunoprecipitated with antibodies monospecific to activase. Expression of the 46-kDa polypeptide ceased within 1 h of the return of heat stressed plants to control conditions. Activase precursors of 55 and 51 kDa were detected among the in vitro translation products of RNA from control and heat stressed plants. In addition, a 53-kDa polypeptide that also immunoprecipitated with anti-activase IgG was among the in vitro translation products of RNA from heat-stressed plants. This putative activase precursor did not occur among the in vitro translation products of RNA from plants that had recovered from heat stress. The levels of the constitutive 47- and 43-kDa activase polypeptides were similar in control and heat-stressed plants, based on immunoblotting with antibodies to activase. However, a 46-kDa cross-reacting polypeptide was also present in heat-stressed plants and constituted about 5% of the total activase after 48 h at high temperature. The identity of the heat-induced 46-kDa polypeptide as activase was confirmed by protein sequencing, which showed that its N-terminal sequence was identical to that of the constitutive 47-kDa activase polypeptide. The presence of multiple isoforms for both the 47- and 43-kDa activase polypeptides on immunoblots of two-dimensional gels and the complex banding pattern on Southern blots together suggest the existence of more than one activase gene and the possibility that the synthesis of the heat-induced activase polypeptide may be regulated transcriptionally. Induction of a new form of activase may constitute a mechanism of photosynthetic acclimation to heat stress in cotton. PMID- 11762162 TI - Activation of the oxidative burst in aequorin-transformed Nicotiana tabacum cells is mediated by protein kinase- and anion channel-dependent release of Ca2+ from internal stores. AB - The source of Ca2+ involved in transducing an oxidative-burst defense signal was examined in aequorin-transformed tobacco (Nicotiana tabacum L.) cells using modulators of Ca2+ entry. Treatments that either increased or decreased the influx of Ca2+ from external stores were found to have little effect on the magnitude or kinetics of an osmotically stimulated oxidative burst. In contrast, treatments that reduced the discharge of Ca2+ from internal stores inhibited dilution-activated H2O2 production. Curiously, most of the modulators commonly employed in animal studies as internal Ca(2+)-release inhibitors were neither effective in blocking discharge of intracellular Ca2+ nor in preventing the oxidative burst. When three different biochemical elicitors of the oxidative burst were similarly examined, both the H2O2 production and Ca2+ fluxes stimulated were found to be sensitive to modulators of internal Ca2+ release, but neither was impacted by alterations in externally derived Ca2+ influx. We hypothesize, therefore, that the oxidative burst does not depend on the influx of external Ca2+, but instead may generally be mediated by the release of internal Ca2+ in a manner that depends on the proper function of kinases and anion channels. These Ca2+ pulses trigger downstream signaling events that include the activation of Ca(2+)-regulated protein kinases, which are required for stimulation of the oxidative burst. PMID- 11762163 TI - Photosynthetic light response curves determined with the leaf oxygen electrode: minimisation of errors and significance of the convexity term. AB - From photosynthetic studies on a range of monocotyledonous (C-3 and C-4) and dicotyledonous (C-3) plants using a leaf oxygen electrode, we conclude the following. (i) A non-linear model [J.H.M. Thornley (1976) Mathematical models in plant physiology, Academic Press, London; B. Marshall and P.V. Biscoe (1980) J Exp Bot 31:29-39] significantly better describes the photosynthetic light response curve [rate of photosynthesis (P) versus incident photosynthetic photon flux density (I)] than the frequently used linear hyperbolic model [E.I. Rabinowich (1951) Photosynthesis and related processes, vol 2, Wiley, New York]. (ii) When used at the recommended CO2 partial pressures (Ca = 1-5 kPa), CO2 supply saturates the photosynthesis rate in the C-3 dicot Phaseolus coccineus L. but not in the C-3 monocot Hordeum vulgare L.. (iii) Fits using a linear hyperbolic model for P versus I produce relatively large and statistically significant errors (approximately 60%) in the estimation of Pmax and quantum efficiency (alpha) if Ca is not > 5 kPa. (iv) The convexity term, theta, incorporated into the non-linear models for P versus I appears to reflect the limitation placed on the carboxylation processes by the supply of CO2 to the chloroplast stroma. Therefore, the use of a non-linear model providing an estimate of theta should be encouraged, as it is likely to provide information on the physiological status of plants. PMID- 11762164 TI - Photosynthetic properties of an Arabidopsis thaliana mutant possessing a defective PsbS gene. AB - We describe the properties of npq4-9, a new mutant of Arabidopsis thaliana (L.) Heynh. with reduced nonphotochemical quenching (NPQ) capacity that possesses a single amino acid substitution in the PsbS gene encoding PSII-S, a ubiquitous pigment-binding protein associated with photosystem II (PSII) of higher plants. Growth, photosynthetic pigment contents, and levels of the major PSII antenna proteins were not affected by npq4-9. Although the extent of de-epoxidatin of violaxanthin to antheraxanthin plus zeaxanthin for leaves displaying the mutant phenotype equaled or exceeded that observed for the wild type, the relative effectiveness of de-epoxidized xanthophylls in promoting NPQ was consistently lower for the mutant. Energy partitioning in PSII was analyzed in terms of the competition for singlet chlorophyll a among the processes of fluorescence, thermal dissipation, and photochemistry. The key processes of NPQ and photochemistry in open PSII centers are represented by the relative in vivo rate constants kN and kP0, respectively. The magnitude of kP0 in normal leaves declined only slightly with increasing kN, consistent with localization of NPQ primarily in the antenna complex. Conversely, a highly significant linear decline in kP0 with increasing kN was observed for the mutant, consistent with a role for the PSII reaction center in the NPQ mechanism. Although the PSII absorption cross section for white light was not significantly different relative to that of the wild type, PSII quantum yield was significantly lower in the mutant. The resulting lower capacity for linear electron transport in the mutant primarily affected reduction of terminal acceptors other than CO2. Parallel measurements of fluorescence and in vivo absorbance at 820 nm indicated a consistently higher steady-state level of reduction of PSII acceptors and accumulation of P700+ for the mutant. This suggests that inter-photosystem electron transport in the mutant is restricted either by a higher transthylakoid delta pH or by diminished accessibility to reduced plastoquinone. PMID- 11762165 TI - Auxin promotes gibberellin biosynthesis in decapitated tobacco plants. AB - Excision of the apical bud (decapitation) of tobacco (Nicotiana tabacum L.) plants reduced the endogenous levels of indole-3-acetic acid (IAA), gibberellin A20 (GA20), and GA1 (the bioactive GA), in internode tissue below the excision site. Application of IAA to the stump of decapitated plants dramatically increased GA20 content, to a level 3-fold greater than in intact plants. Gibberellin A1 content was also increased by IAA. Decapitation reduced the conversion of [14C]GA19 to [14C]GA20 and of [14C]GA20 to [14C]GA1, and appeared to promote the deactivation pathway [14C]GA20 to [14C]GA29 to [14C]GA29 catabolite. Application of auxin counteracted these effects, but did not restore the conversion of [14C]GA20 to [14C]GA1 to the level found in intact plants. The results indicate that auxin is necessary for normal GA biosynthesis in stems of tobacco. PMID- 11762166 TI - Changes in stomatal behaviour in the calcicole Leontodon hispidus due to the disruption by ozone of the regulation of apoplastic Ca2+ by trichomes. AB - Regulation of the concentration of Ca2+ in the apoplast of plants is essential in order to allow Ca(2+)-dependent processes, such as Ca(2+)-mediated signal transduction in stomatal guard cells, to function correctly. This is particularly important for plants growing with high levels of Ca2+ in the rhizosphere. Recently, we have shown that in two calcicoles, Leontodon hispidus L. and Centaurea scabiosa L., trichomes play a key role in this regulatory process. Ozone is known to have a marked effect on plant Ca2+ homeostasis. Therefore, we have examined the effect of this pollutant on the regulation by trichomes of apoplastic Ca2+ in the calcicole L. hispidus. Treatment with 100 nl l-1 ozone resulted in a reduction in stomatal conductance of approximately 25% in plants grown with 15 mM Ca2+ in the rhizosphere. Analysis of total Ca2+ levels revealed that these changes in stomatal behaviour reflect a decrease in the ability of trichomes to sequester Ca2+. The amount of Ca2+ present in the trichome tip cell was reduced by approximately 38%. This was accompanied by an increase in the levels of Ca2+ in the guard cells and other tissues of the leaf. These data suggest that ozone has a detrimental effect on the ability of trichomes to regulate the concentration of apoplastic Ca2+ in L. hispidus, resulting in altered stomatal behaviour, and hence gaseous exchange, possibly due to the disruption of guard-cell Ca(2+)-mediated signal transduction. This has important implications for the growth and survival of plants growing in Ca(2+)-rich soils. PMID- 11762167 TI - Inhibition of cell proliferation, cell expansion and differentiation by the Arabidopsis SUPERMAN gene in transgenic tobacco plants. AB - Plant development depends upon the control of growth, organization and differentiation of cells derived from shoot and root meristems. Among the genes involved in flower organ determination, the cadastral gene SUPERMAN controls the boundary between whorls 3 and 4 and the growth of the adaxial outer ovule integument by down-regulating cell divisions. To determine the precise function of this gene we overexpressed ectopically the Arabidopsis thaliana (L.) Heynh. SUPERMAN gene in tobacco (Nicotiana tabacum L.). The transgenic plants exhibited a dwarf phenotype. Histologically and cytologically detailed analyses showed that dwarfism is correlated with a reduction in cell number, which is in agreement with the SUPERMAN function in Arabidopsis. Furthermore, a reduction in cell expansion and an impairment of cell differentiation were observed in tobacco organs. These traits were observed in differentiated vegetative and floral organs but not in meristem structures. A potential effect of the SUPERMAN transcription factor in the control of gibberellin biosynthesis is discussed. PMID- 11762168 TI - Early primordium morphogenesis during lateral root initiation in Arabidopsis thaliana. AB - The first morphogenetic events of lateral root primordium (LRP) formation in the Arabidopsis thaliana (L.) Heynh. pericycle occur soon after cells of the primary root complete elongation. Pericycle cells in direct contact with underlying protoxylem cells participate in LRP formation. Two types of LRP initiation were found, longitudinal uni- and bi-cellular. These occur when a single or two pericycle cells within a file, respectively, become founder cells for the entire longitudinal extent of the LRP. Histochemical and cytological analysis suggests that three is the minimum number of cells required to initiate an LRP. In young primordia comprising less than 32 cells, the average cell-doubling time was 3.7 h, indicating a drastic acceleration of cell cycle progression after lateral root initiation. Early in LRP development, cell growth is limited and therefore cytokinesis leads to a reduction of cell volume, similar to cleavage division cycles during animal and plant embryogenesis. The striking coordination of proliferation between pericycle cells in adjacent files in direct contact with the underlying protoxylem implies that intercellular signaling mechanisms act in the root apical meristem or later in development. PMID- 11762169 TI - Analysis of the distribution of copper amine oxidase in cell walls of legume seedlings. AB - Copper-containing amine oxidase (CuAO) has been proposed to play a role in H2O2 production in plant cell walls during cell development and in response to pathogen attack. We have compared the localisation of CuAO in pea (Pisum sativum L.), lentil (Lens culinaris M.) and chick pea (Cicer arietinum L.) grown under different light conditions, using both immuno- and histochemical techniques. The enzyme was detected by indirect immunofluorescence in the cell walls of parenchyma tissues of etiolated pea and lentil plants and was particularly abundant at intercellular spaces. Upon de-etiolation, CuAO largely disappeared from cortical cell walls except in the region of intercellular spaces. In the apical internode of light-grown seedlings, CuAO occurred mainly in cortical cell walls and, to some extent, in cell walls of xylem vessels. In both the elongation zone and mature regions of roots, CuAO was restricted to cortical cell walls and some cell junctions close to the meristem. Extensin epitopes co-localised to intercellular spaces of the cortex in de-etiolated pea, indicating that CuAO may have a role in cell wall strengthening at intercellular spaces. In chick pea, the localisation of the enzyme varied between different cultivars that have differing susceptibility to the fungus Ascochyta rabiei. In a susceptible cultivar Calia, immunogold labelling localised CuAO to cell walls of the cortex, as in lentil and pea, while in a resistant cultivar Sultano, it was most abundant in xylem vessels and, in light-grown plants, in the epidermis. These expression patterns are discussed with regard to the possible functions of amine oxidase in cell growth, cell differentiation and pathogen resistance. PMID- 11762170 TI - A strain of Synechocystis sp. PCC 6803 without photosynthetic oxygen evolution and respiratory oxygen consumption: implications for the study of cyclic photosynthetic electron transport. AB - Cyclic electron transport around photosystem (PS) I is believed to play a role in generation of ATP required for adaptation to stress in cyanobacteria and plants. However, elucidation of the pathway(s) of cyclic electron flow is difficult because of low rates of this electron flow relative to those of linear photosynthetic and respiratory electron transport. We have constructed a strain of Synechocystis sp. PCC 6803 that lacks both PSII and respiratory oxidases and that, consequently, neither evolves nor consumes oxygen. However, this strain is still capable of cyclic electron flow around PSI. The photoheterotrophic growth rate of this strain increased with light intensity up to an intensity of about 25 mumol photons m-2 s-1, supporting the notion that cyclic electron flow contributes to ATP generation in this strain. Indeed, the ATP-generating ability of PSI is demonstrated by the fact that the PSII-less oxidase-less strain is able to grow at much higher salt concentrations than a strain lacking PSI. A quinone electrode was used to measure the redox state of the plastoquinone pool in vivo in the various strains used in this study. In contrast to what is observed in chloroplasts, the plastoquinone pool was rather reduced in darkness and was oxidized in the light. This is in line with significant electron donation by respiratory pathways (NADPH dehydrogenase and particularly succinate dehydrogenase) in darkness. In the light, the pool becomes oxidized due to the presence of much more PSI than PSII. In the oxidase-less strains, the plastoquinone pool was very much reduced in darkness and was oxidized in the light by PSI. Photosystem II activity did not greatly alter the redox state of the plastoquinone pool. The results suggest that cyclic electron flow around PSI can contribute to generation of ATP, and a strain deficient in linear electron transport pathways provides an excellent model for further investigations of cyclic electron flow. PMID- 11762171 TI - Seasonal changes in temperature and light drive acclimation of photosynthetic physiology and macromolecular content in Lobaria pulmonaria. AB - Lobaria pulmonaria (L.) Hoffm. is an epiphytic lichen common to temperate deciduous forests where it copes with large changes in temperature and light levels through repeated annual cycles. Samples of L. pulmonaria were taken from a deciduous forest in southeastern Canada at 35-day intervals from February 1999 to February 2000 and also from a rare population in an evergreen forest in March and August 1999. At field-ambient temperatures and light levels, the realised photosystem II (PSII) electron transport was low both in the summer and winter, with transient peaks in the spring and autumn. In contrast, the seasonal pattern of potential electron transport measured at a fixed 20 degrees C peaked in winter, showing the importance of temperature in driving photosynthesis to low levels in the winter despite an acclimation of electron-transport potential to exploit the high ambient light. Realised gross CO2 uptake was correlated with PSII electron transport at mechanistically plausible rates at all sampling sites in the summer but not in the winter, indicating electron diversion away from CO2 fixation in the winter. Chlorophyll content was highest in the dark summer months. The amount of ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) large subunit (LSU) was highest in spring. Changes in the level of this hyperabundant protein and in the activity of PSII maintained a relatively constant rate of maximum CO2 uptake per RuBisCO LSU from April through November, despite great changes in the seasonal light and temperature. L. pulmonaria acclimates between light and temperature stress in the winter months to light limitation in the dark summer months. Transition intervals in the spring and autumn, with warm, bright and wet conditions, are likely the most amenable times for growth. PMID- 11762172 TI - Effects of the mur1 mutation on xyloglucans produced by suspension-cultured Arabidopsis thaliana cells. AB - Mutation of the Arabidopsis thaliana (L.) Heynh. gene MUR1, which encodes an isoform of GDP-D-mannose-4,6-dehydratase, affects the biosynthetic conversion of GDP-mannose to GDP-fucose. Cell walls in the aerial tissues of mur1 plants are almost devoid of alpha-L-fucosyl residues, which are partially replaced by closely related alpha-L-galactosyl residues. A line of suspension-cultured A. thaliana cells was generated from leaves of mur1 plants and the structure of the xyloglucan in the walls of these cells was structurally characterized. Xyloglucan fractions were prepared from the walls of both wild-type (WT) and mur1 cells by sequential extraction with a xyloglucan-specific endoglucanase (XEG) and aqueous KOH. Structural analysis of these fractions revealed that xyloglucan produced by cultured mur1 cells is similar, but not identical to that isolated from leaves of mur1 plants. As previously reported for mur1 leaves, the xyloglucan from cultured mur1 cells contains less than 5% of the fucose present in the xyloglucan from WT cells. Fucosylation of the xyloglucan is substantially restored when mur1 cells are grown in medium supplemented with L-fucose. Xyloglucan isolated from leaves contains more oligosaccharide subunits in which the central sidechain is terminated with a beta-D-galactosyl residue than does xyloglucan prepared from cultured cells. This was observed for both mur1 and WT plants, indicating that this correlation is independent of the mur1 mutation and that it is possible to distinguish changes due to genetic mutation from those due to the physiological state of the cells in culture. Suspension-cultured cells thus provide a convenient source of genetically altered cell wall material, facilitating the biochemical characterization of mutations that affect cell wall structure. PMID- 11762173 TI - Diverse chalcone synthase superfamily enzymes from the most primitive vascular plant, Psilotum nudum. AB - Psilotum nudum Griseb is a pteridophyte and belongs to the single family (Psilotaceae) of the division, Psilophyta. Being the only living species of a once populated division, P. nudum is the most primitive vascular plant. Chalcone synthase (CHS; EC 2.3.1.74) superfamily enzymes are responsible for biosyntheses of diverse secondary metabolites, including flavonoids and stilbenes. Using a reverse transcription-polymerase chain reaction strategy, four CHS-superfamily enzymes (PnJ, PnI, PnL and PnP) were cloned from P. nudum, and heterologously expressed in Escherichia coli. These four enzymes of 396-406 amino acids showed sequence identity of > 50% among themselves and to other higher-plant CHS superfamily enzymes. PnJ and PnP preferred p-coumaroyl-CoA and isovaleryl-CoA respectively, as starter CoA and catalyzed CHS-type ring formation, indicating that they are CHS and phlorisovalerophenone synthase, respectively. On the other hand, PnI and PnL preferred cinnamoyl-CoA as starter CoA and catalyzed stilbene synthase-type cyclization and thus were determined to be pinosylvin synthases (EC 2.3.1.146). In addition, PnE, which uniquely contains a glutamine in place of otherwise strictly conserved histidine, had no apparent in vitro catalytic activity. Phylogenetic analysis indicated that these P. nudum clones form a separate cluster together with Equisetum arvense CHS. This cluster of pteridophytes is located next to the cluster formed by pine (gymnosperm) enzymes, in agreement with their evolutionary relationships. Psilotum nudum represents a plant with the most diverse CHS-superfamily enzymes and this ability to diverge may have provided a survival edge during evolution. PMID- 11762174 TI - The location of (1-3)-beta-glucan in the nucellar projection and in the vascular tissue of the crease in developing barley grain using a (1-3)-beta-glucan specific monoclonal antibody. AB - Immunocytochemical localization of the (1-3)-beta-glucan, callose, in developing barley (Hordeum vulgare L.) grain was investigated using a specific monoclonal antibody and observed by means of confocal laser-scanning microscopy. The nucellar projection (NP) and vascular tissue (VT) of the crease cells were specifically labelled by this antibody at all stages of grain development. Maximum intensity of label was found in the NP at 12-15 days post anthesis; thereafter, label was localized in the VT of the crease. The location of (1-3) beta-glucan in the NP and VT of the crease was also monitored by means of aniline blue-induced fluorescence of callose. The results obtained using both methods were found to be similar. The possible significance of the presence of callose in these tissues is discussed in relation to the uptake of assimilates into the developing grain. PMID- 11762175 TI - The diffusive transport of gibberellins and abscisic acid through the aleurone layer of germinating barley grain: a mathematical model. AB - A mathematical model of the diffusive transport of abscisic acid (ABA) and gibberellins (GAs) through the aleurone layer of barley (Hordeum vulgare L.) grain is presented. The model consists of two partial differential equations describing the accumulation of phytohormone in the apoplastic and symplasmic compartments of the aleurone layer, both spatially and temporally. The mathematical model contains the morphology of the barley grain and the physicochemical properties of the two phytohormones. A mathematical derivation of the accumulation ratios for the two phytohormones between the symplast and apoplast under equilibrium conditions resulted in different distribution mechanisms for GAs and ABA. A sensitivity analysis of the accumulation ratio for GAs indicated high sensitivity to the apoplastic pH and the membrane potential, whereas the accumulation ratio for ABA proved to be most sensitive to the pH difference between the apoplast and symplast. The diffusive transport time for GAs to the basal site of the aleurone layer as calculated with the mathematical model is within a physiologically plausible timescale according to experimental data from the literature. Abscisic acid cannot be transported by diffusion to the end of the aleurone layer as quickly as GAs, according to model simulations. Therefore, the functional role of ABA in germination is likely to be in the vicinity of the embryo. PMID- 11762176 TI - Characterization and regulation of ammonium transport systems in Citrus plants. AB - We have investigated both the kinetics and regulation of 15NH4+ influx in roots of 3-month-old hydroponically grown Citrus (Citrus sinensis L. Osbeck x Poncirus trifoliata Blanco) seedlings. The 15NH4+ influx is saturable below an external ammonium concentration of 1 mM, indicating the action of a high-affinity transport system (HATS). The HATS is under feedback repression by the N status of the plant, being down-regulated in plants adequately supplied with N during growth, and up-regulated by N-starvation. When assayed between 1 and 50 mM [15NH4+]0, the 15NH4+ influx showed a linear response typical of a low-affinity transport system (LATS). The activity of the LATS increased in plants supplied with NH4+ as compared with plants grown on an N-free medium. Transfer of the plants to N-free solution resulted in a marked decrease in the LATS-mediated 15NH4+ influx. Accordingly, resupply of NH4+ after N-starvation triggered a dramatic stimulation of the activity of the LATS. These data provide evidence that in Citrus plants, the LATS or at least one of its components is inducible by NH4+. Even when up-regulated, both the HATS and the LATS displayed a limited capacity, as compared with that usually found in herbaceous species. The use of various metabolic uncouplers or inhibitors indicated that 15NH4+ influx mediated by the HATS is strongly dependent on energy metabolism and H+ transmembrane electrochemical gradient. By contrast, the LATS is not affected by protonophores or inhibitors of the H(+)-ATPase, suggesting that its activity is mostly driven by the NH4+/NH3 transmembrane gradient. In agreement with these hypotheses, the HATS-mediated 15NH4+ influx was strongly inhibited when the solution pH was raised from 4 to 7, whereas influx mediated by the LATS was slightly stimulated. PMID- 11762177 TI - [Multicenter open study with docetaxel. Treatment of patients with locally advanced or metastatic breast carcinoma]. AB - The efficacy and safety of docetaxel were evaluated in an open, multicentric, non comparative study involving 24 patients with locally advanced or metastatic breast cancer, eligible for second line or subsequent anticancer chemotherapy; the results confirm a global response around 50%, suggesting some advantages when compared to the usual treatments in this set of patients; the median duration of response, the median time to progression and the median time of survival were respectively, 309, 219 and 345 days; the main iatrogenic event was haematological, mainly in the white and red blood cells. PMID- 11762178 TI - [Intestinal invagination in children. Reduction with pneumo-enema]. AB - Pneumatic reduction of intussusception in children is an effective and safe procedure, although controversy persists concerning contraindications. The shown by this procedure when compared to barium reduction have led to its implementation in our Service. AIM: To evaluate the usefulness of a 'handicraft method' of pneumatic reduction of intussusception with very restricted contraindications (peritonitis or shock). MATERIAL AND METHODS: The prospective study included 50 attempts at pneumatic reduction in 48 children (age range: 1.5 24 months). After confirmation of the diagnosis by ultrasonography. Then, air insufflation of the colon was performed under manometric and fluoroscopic control. After confirmation of diagnosis by ultrasonography, air insufflation of the colon was performed under manometric and fluoroscopic control in an operative room. Evolution longer than 24 hours was considered diagnostic delay, leukocytosis if WBC > 15 x 10(9)/l and distal localisation after splenic angle. Immediate laparotomy was undertaken in case of unsuccessful or doubtful reduction. RESULTS: Thirty-five reduction procedures (70%) were effective ab initio. In the 15 children submitted to laparotomy, seven were completely reduced (14%), five were manually reduced (10%), two presented intestinal necrosis (4%) and one (recurrence) had an ileal duplication (2%). The "real" efficacy (84%) was lower, even though significantly affected by diagnostic delay (81% vs 83%), rectal bleeding (81% vs 100%) or leukocytosis (71% vs 81%); efficacy was significantly lower only in distal localised cases (67% vs 97%, p = 0.02). There was one more recurrence (4%) and no other complications. CONCLUSIONS: The adopted method of pneumatic reduction was highly effective with low morbidity. Restricted contraindications were appropriate. PMID- 11762179 TI - [Oral health in pregnancy]. AB - Descriptive study with an analytic component, on pregnant women that went for consultation to Maternidade Daniel de Matos (Coimbra, Portugal) during the second week of July 1997. 80 women were randomly selected and asked to answer a questionnaire, concerning level of knowledge towards oral health as well as dietary and oral hygiene habits before and during pregnancy. It was also quantified the dental plaque indicator by using a plaque staining method. The knowledge about oral health is globally speaking, insufficient; dietary habits are mainly cariogenic although pregnant women tend to lower their sugar intake. During pregnancy women rarely go to see the dentist, especially the less educated ones. The dental plaque levels are globally high, indicating oral hygiene habits of low quality. PMID- 11762180 TI - [Evaluation of analgesia after cesarean section]. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of post-caesarean analgesia comparing three techniques most frequently used. PATIENTS AND METHODS: For three months all pregnant women submitted to elective or urgent caesarean section, under general or regional anaesthesia, were evaluate with a total of 129 parturient. These parturient were divided into three groups with different techniques of postoperative analgesia: Group 1 (n = 26) received intravenous pethidine and paracetamol per os, group 2 (n = 58) received epidural morphine and group 3 (n = 45) epidural morphine and intravenous propacetamol. Pain was assessed at rest and during mobilisation using a scale of 0-without pain, 1-mild pain, 2-moderate pain and 3-severe pain. Overall satisfaction was assessed with a verbal qualitative scale of very good, good, sufficient and bad. Side effects were analysed. RESULTS: The records of pain at rest and during mobilisation were significantly lower with epidural analgesia compared with intravenous pethidine. There were no significant differences between groups 2 and 3. Similar results were observed in the degree of satisfaction. For 50% of parturient of epidural analgesia (groups 2 and 3) and only 4% of intravenous pethidine (group 1) the analgesic technique was very good. Propacetamol and epidural morphine (group 3) had better pain scores (very good and good) when compared with morphine alone (group 2) but there were no significant differences. Epidural morphine was associated with more pruritus. CONCLUSION: From this study we are able to conclude that epidural morphine offers a good quality of analgesia with better satisfaction and minimal side effects. PMID- 11762181 TI - [Assessment of fetal well-being during labor]. AB - Nowadays the intrapartum assessment of fetal well-being and obstetric intervention during labor demand careful clinical examination and the knowledge of techniques such as cardiotocography, amnioinfusion, fetal scalp blood sampling and ultrasonography. The diversity of methods demands understanding and interpretation of fetal distress signals. The aim of this paper is to give a possible guidance in intrapartum assessment of fetal well-being. PMID- 11762182 TI - [Advanced glycosylation in diabetes mellitus. Occurrence of late complications]. AB - Chronic hyperglycaemia contributes to tissue and organ damage retina, kidney and nerves by promoting the formation of advanced glycosylation end products (AGE). The AGE accumulation both in intra and extracellular proteins plays an essential role in the pathogenesis of diabetic complications by production of cross links on extracellular matrix proteins, by interaction with specific cellular receptors and by modification of nucleic acids. Human studies are being conducted to examine the pharmacokinetics efficacy and toxicity of pharmacologic agents that inhibit the AGE formation--aminoguanidine and aminoguandine-like--in order to define its role in the prevention and treatment of retinopathy, nephrology, neuropathy and diabetic atherosclerosis. PMID- 11762183 TI - [Primary immunodeficiency secondary to ZAP-70 deficiency]. AB - The authors present the case of a child with recurrent infections since the age of 4 months, including bilateral pneumonia by Pneumocystis carinii and protracted varicella. Serum immunoglobulin values (when 10 months old), and B cell values were normal. There was persistent lymphocytic leucocytosis, near absence of CD8+ cells, and an increased CD4/CD8 ratio. The percentage of activated T cells and the expression of HLA class I were normal. Proliferation, activation and IL-2 synthesis studies in T cells showed a TCR/CD3-associated signal transduction deficit. ZAP-70 cDNA sequencing showed a mutation, and no ZAP-70 protein was detected in T cells. ZAP-70 deficiency is associated with a rare immune deficiency with absence of CD8+ T cells as well as a functional deficiency in T cells. Seven months after bone marrow transplantation the child is clinically well and immunologically recovered. PMID- 11762184 TI - [Endovascular treatment of iliac artery aneurysm]. AB - The authors report a case of an aneurysm of the common iliac artery of atherosclerotic etiology, treated by percutaneous endoluminal stent-graft placement. They describe the technique and review the medical literature. PMID- 11762185 TI - [Malignant angiotropic lymphoma. With primary lung involvement]. AB - Angiotropic malignant lymphoma (AMLy) is a rare neoplasm characterized by the intravascular proliferation of large lymphoid cells. Most of the cases reported in the literature describe a predominant involvement of the central nervous system and skin. Although any organ may be afflicted, primary involvement of the lung is unusual. We report a case of AMLy in which the pulmonary symptoms dominate the clinical picture. The tumour cells inside the small vessels of the lung were positively identified as B-phenotype lymphoid cells by immunoperoxidase stains for CD-20, which is typical of this aggressive type of lymphoma. PMID- 11762186 TI - [Progressive myositis ossificans. Stone man]. AB - Myositis ossificans progressiva (MOP) is a rare hereditary connective tissue disease, genetically inherited as an autossomal dominant trait with complete penetrance but variable expression. The onset usually takes place during childhood and progressive involvement of the spinal cord and proximal extremities leads to immobilization and articular dysfunction. We present a case of a 29-year old woman with the typical features of MOP and review the pathogenesis, clinical manifestations and treatment options of this rare disease. PMID- 11762187 TI - [Malignant localized fibrous tumor of the pleura]. AB - The authors report a case of a localized fibrous tumour of the pleura with huge proportions of 26 x 14 x 12 cm and 1.25 Kgr of weight, in a 56 year old female patient. The tumour occupied practically the inferior 2/3 of the right pulmonary field and had an unusual insertion in the diaphragmatic parietal pleura. It was non pediculous and had histological features of malignancy. The diagnosis of localized fibrous tumour of the pleura was achieved through observation of the sample obtained by fine needle aspiration. The immunohistochemical study subsequently done on the surgical specimen, confirmed the previous diagnosis. The evaluation of malignancy was based ou the following histological criteria: high cellularity, cellular pleomorphism, mitotic activity (more than four mitotic figures per 10 high power fields), hemorrhagic areas and necrosis. PMID- 11762188 TI - [Cancer screening. Concepts, trends, and practices]. AB - A National Cancer Surveillance Program has begun in Portugal in 1990. However, it is unevenly applied throughout the country and is almost unknown to clinicians other than general practitioners. As potentially life-saving procedures, cancer screening and early detection have an important impact not only among physicians but also among the general public, making it absolutely necessary an harmony of rationale, guidelines and practices. The author summarizes the points in discussion concerning cancer prevention procedures, the different published guidelines and some numbers on its practices. The aim is a contribution to an improvement in cancer screening in Portugal, achievable through awareness, promotion of evidence evaluation and the pursuit of consensus in strategies. PMID- 11762189 TI - [Implantation of an intra-hospital resuscitation program]. AB - The authors present their own experience on the installation of an in-hospital resuscitation programme, in a new tertiary hospital with 400 beds, an ICU with 8 beds and an emergency room 24 hours per day. The most important features presented are: the support by the Board of the Hospital, the engagement of all the health professionals, the distribution standardization and maintenance of the resuscitation equipment, the training in basic life-support techniques the doctors and nurses in the hospital, the performance of the cardiac arrest teams, all of which are fundamental to the maintenance of the chain of survival of cardiopulmonary resuscitation. PMID- 11762190 TI - The gene and pseudogenes of Cbx3/mHP1 gamma. AB - The HP1 class of chromobox (Cbx) genes encode an evolutionarily conserved family of proteins involved in the packaging of chromosomal domains into a repressive heterochromatic state. The murine Cbx5, Cbx1 and Cbx3 genes encode the three mouse HP1 proteins, mHP1 alpha, -beta and -gamma respectively. Here, we report the cloning of the mouse Cbx3/HP1 gamma gene and the chromosomal localisation of Cbx3 and three Cbx3-related pseudogenes. The Cbx3 structural gene is located on mouse Chromosome 6, close to the Hoxa cluster. Two Cbx3 processed pseudogenes are separated by just 300 bp and are arranged in a head-to-tail configuration on Chromosome 13 while a third pseudogene is found on mouse Chromosome 4. The genomic intron-exon arrangement of Cbx3 is different from the conserved organisation of three other mammalian HP1 genes, Cbx1 (mHP1 beta), CBX3 (hHP1 gamma), and Cbx5 (mHP1 alpha) in that Cbx3 lacks an intron that is present in the others. PMID- 11762191 TI - Molecular cloning, characterization, and tissue-specific expression of human LANCL2, a novel member of the LanC-like protein family. AB - We identified and characterized the cDNA coding for human LANCL2, a new member of the eukaryotic LanC-like protein family which is related to the bacterial lanthionine synthetase components C (LanC). The composite nucleotide sequence revealed a coding region of 1353 bp, a 5'-UTR of 186 bp and a 3'-UTR of 2421 bp. The deduced sequence of 450 amino acids showed 57.9% identity (74.7% similarity) when compared with the human LANCL1 homologue. In contrast to LANCL1, a unique ATP/GTP-binding site motif A was found in LANCL2. Northern blot analysis revealed the presence of two major transcripts in the brain, 4.7 kb and 4.1 kb in size, and a major 1.8 kb transcript in testis. Accordingly, expression array analysis showed prominent signals in these tissues. Because of the structural similarity to LanC, we postulate that LANCL2 may play a role as a component of a peptide modifying complex. PMID- 11762192 TI - xln23 from Streptomyces chattanoogensis UAH23 encodes a putative enzyme with separate xylanase and arabinofuranosidase catalytic domains. AB - The xylanase gene xysA of Streptomyces halstedii JM8 was used to isolate a DNA fragment from a gene library of Pstl-digested chromosomal DNA of the lignocellulolytic actinomycete Streptomyces chattanoogensis CECT-3336. Nucleotide sequence analysis revealed a gene (xln23) encoding a bifunctional multimodular enzyme bearing two independent xylanase and alpha-L-arabinofuranosidase domains separated by a Ser/Gly-rich linker. The N terminus of the predicted protein showed high homology to family F xylanases. The C terminus was homologous to amino acid sequences found in enzymes included in the glycosyl hydrolase family 62 and, in particular, to those of alpha-L-arabinofuranosidase AbsB from Streptomyces lividans. PCR and RT-PCR experiments showed that the nucleotide sequences corresponding to each domain are arranged as expected on the chromosomal DNA and that they are cotranscribed. To our knowledge, this is the first description of xylanase and arabinofuranosidase domains in a same open reading frame. PMID- 11762193 TI - Cloning and characterisation of the Hint homologue of the thermophile Thermus thermophilus. AB - Screening of a genomic library of the thermophile Thermus thermophilus revealed a novel thermophilic hint gene, homologues of which are highly conserved in genera from archaea to mammals. Hint belongs to the HIT protein super-family, which contains two broad groups, Fhit, associated with tumour suppression in eukaryotes and Hint with putatitively protein kinase C inhibitory activity. In T. thermophilus the 321 bp gene has a GC content of 67% overall and 94.4% in the third nucleotide position, with unusually no thymine as a wobble base. The gene product, a small highly conserved 11,996 Da predicted soluble cytoplasmic protein, offers an ideal opportunity to investigate thermostabilising amino acid substitutions. Here we report on the characterisation of the novel hint sequence. PMID- 11762194 TI - Identification of a gene cluster for the mevalonate pathway in Lactobacillus helveticus. AB - Three Lactobacillus helveticus 53/7 genes essential for the biosynthesis of isopentenyl diphosphate and the gene coding for a putative carotenoid biosynthesis protein were for the first time identified from lactic acid bacteria. The deduced amino acid sequences of the mevalonate pathway gene products share significant identity with corresponding proteins of a few gram positive cocci and Streptomyces species. PMID- 11762195 TI - Sequence analysis of the rat phenylalanine hydroxylase gene promoter. AB - We have characterized the 5'-end (3218 bp) of the rat phenylalanine hydroxylase (PAH) gene. Within this PAH promoter sequence, we have identified a number of putative regulatory sites analogous to those present in the human and murine PAH promoters. In particular, potential HNF 1 binding sites and a CRE have been identified. These sequences respectively bind HNF1 and CREB transcription factors present in rat nuclear extracts and may be significant in the tissue-specific and hormonal control of PAH expression. PMID- 11762196 TI - Identification and sequence determination of mRNAs detected in dormant (diapausing) Aedes triseriatus mosquito embryos. AB - Many insects survive adverse climatic conditions in a dormant state known as diapause. In this study, we identified and sequenced several mRNAs in diapausing Aedes triseriatus mosquito embryos. Using reverse-transcription PCR and 5' RACE, we identified a 995-nucleotide cDNA that encodes a 259-amino acid protein of unknown function. This putative protein displays strong sequence similarity to Drosophila melanogaster (95%), human (87%), Caenorhabditis elegans (86%) and yeast (81%) counterparts. The second identified full-length cDNA consists of 624 nucleotides and encodes a 174-amino acid protein of unknown function. This putative protein displays significant sequence similarity to D. melanogaster (68%), human (59%), plant (57%) and yeast (49%) counterparts. We also detected a number of cDNA fragments that exhibited significant sequence similarity to a mitochondrial cytochrome C oxidase subunit, human N33 protein (a potential human prostate tumor suppressor), 18S and 28S ribosomal RNAs, protein disulfide isomerase, and guanine nucleotide-binding protein. PMID- 11762197 TI - Complete cDNA and deduced amino acid sequence of the chaperonin containing T complex polypeptide 1 (CCT) delta subunit from Aedes triseriatus mosquitoes. AB - The chaperonin containing t-complex polypeptide 1 (CCT) assists in the ATP dependent folding and assembly of newly translated actin and tubulin in the eukaryotic cytosol. CCT is composed of eight different subunits, each encoded by an independent gene. In this report, we used RT-PCR amplification and 5'- and 3' rapid amplification of cDNA ends (RACE) to determine the complete cDNA sequence of the CCT delta subunit from Aedes triseriatus mosquitoes. The CCT delta cDNA is 1936 nucleotides in length and encodes a putative 533 amino acid protein with a calculated molecular mass of 57,179 daltons and pI of 7.15. Hydrophobic residues comprise 39.8% of the amino acid sequence and putative motifs for ATP-binding and ATPase-activity are present. The amino acid sequence displays strong sequence similarity to Drosophila melanogaster (92%), human (85%), puffer fish (84%) and mouse (84%) counterparts. CCT delta mRNA was detected in both biosynthetically active (embryonating) and dormant (diapausing) Ae. triseriatus embryos by RT-PCR analysis. PMID- 11762198 TI - Cloning of rat calcium-modulating cyclophilin ligand. AB - Rat calcium-modulating cyclophilin ligand (CAML) cDNA was cloned and sequenced. It has a predicted open reading frame of 294 amino acids. The CAML gene is highly conserved throughout species, showing 85, 89 and 69% amino acid sequence identity to the human, mouse, and chicken genes, respectively. Gene expression data using astrocytes, microglia and neurons show that CAML mRNA and protein is constitutively expressed in these cell types of the central nervous system. The cloning of rat CAML will facilitate further investigations on the function of this molecule. PMID- 11762199 TI - Immunization with HIV-1 subtype B gp160-DNA induces specific as well as cross reactive immune responses in mice. AB - BACKGROUND & OBJECTIVES: HIV-1 gp160 is an important structural protein for the virus cell interaction and virus entry. Therefore, it is regarded as the most important target for HIV-1 vaccine development. In this study we investigated the use of HIV-1 gp160-DNA construct in eliciting specific and cross reactive cell mediated immune response in mice. METHODS: DNA segment encoding env, tat and rev genes of HIV-1 subtype B (strain BRU-2) was amplified and cloned into mammalian expression vector pCI to generate plasmid pCIBRU-TRE. Mice were injected intramuscularly four times at biweekly intervals with 100 micrograms/dose of pCIBRU-TRE in normal saline, and subsequently analysed for anti HIV-envelope (env) immune responses. RESULTS: A low antibody level was detected as determined by ELISA after 4 doses. Subsequent inoculations failed to increase the antibody titres significantly. Spleen cells from the immunized mice were used for the detection of cellular immune response by lymphocyte proliferation assays (LPA), in vitro production of cytokines and cytotoxic T lymphocyte (CTL) assays. T cell response which was seen from the second week onwards, persisted even at the end of 24 wk following the last dose. Similar levels of T cell proliferation were observed on stimulation with either homologous or heterologous peptides. Cytokine studies showed a Th1 type of response. A cross clade MHC class I restricted CTL response was observed against target cells stimulated with either homologous or heterologous HIV antigens. INTERPRETATION & CONCLUSION: This study demonstrated that DNA encoding full length HIV-1 env glycoprotein gp160 induces specific as well as cross reactive cell mediated immune responses in mice. However, the induction of antibody response was poor. PMID- 11762200 TI - Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa. AB - During the months of May-June 2000, 194 patients with watery diarrhoea were admitted to the Infectious Diseases Ward of the M.K.C.G. Medical College, Berhampur. Ninety four rectal swabs were collected and processed according to the standard procedures. Vibrio cholerae strains were isolated from 20 samples. Of these 20 isolates, two were found to be V. cholerae O1 EITor Ogawa strain and 18 were confirmed to be V. cholerae serotype O139. All V. cholerae O139 isolates were of a single phage type (phage type 1) and the two O1 strains were of phage type 3 and phage type 27 respectively. All 20 V. cholerae isolates were positive for CAMP test, and showed uniform resistance to furazolidone and sensitivity to co-trimoxazole, amoxycillin, norfloxacin, tetracycline and gentamycin. V. cholerae O139 serotype has not been reported earlier in south Orissa. This is probably the first report of its isolation from this area. PMID- 11762201 TI - Campylobacter species associated with diarrhoea in patients from a tertiary care centre of north India. AB - BACKGROUND & OBJECTIVES: Most laboratories do not routinely distinguish the various Campylobacter species, though almost all Campylobacter species have been isolated from human faeces. The epidemiological and clinical aspects of its infection and the species involved in genesis of diarrhoea are least understood in the developing countries. The aim of the present study was to find out frequency of Campylobacter species isolated from patients with diarrhoea over a 12-year period and to analyse their features. METHODS: Campylobacter strains isolated from stool samples of patients with diarrhoea were identified to the species level on appropriate media at 42 degrees C micro-aerobically. Patients' demography and clinical data were analyzed retrospectively; 25 Campylobacter jejuni strains were tested for toxin production and 23 strains were typed by Penner scheme. RESULTS: A total of 62 strains were isolated from 59 patients and the various species were C. jejuni 51 (82.3%), C. coli 8 (12.9%), C. lari 2 (3.2%), and C. upsaliensis 1 (1.6%). Children < 5 yr of age were most affected (34/59; 57.6%), followed by patients in 15-30 yr of age (12/59; 20.3%). Presentation of watery diarrhoea was significantly more common than inflammatory diarrhoea (50/59, 84.7% vs 9/59, 15.3%; P < 0.001). Recurrence occurred in 3 (5.1%) patients. Majority of the infections resolved within one week; one HIV positive patient had chronic diarrhoea. Two patients developed Guillain-Barre syndrome following Campylobacter infection. Twenty (80%) of 25 strains were toxigenic and 20 (87%) of 23 strains could be typed by Penner scheme. INTERPRETATION & CONCLUSION: In our patients, 4 different Campylobacter species and various C. jejuni serotypes were involved in gastroenteritis. Majority of the infections were watery diarrhoea and in children < 5 yr of age. There is a need of a population-based systematic study to know the epidemiology of whole spectrum of campylobacters in India. PMID- 11762202 TI - Oviposition attractancy of an infusion from a wood inhabiting fungus for vector mosquitoes. AB - BACKGROUND & OBJECTIVES: Review of literature indicates that none of the chemicals so far studied for oviposition attractancy was found to be promising for operational use. Efforts are being made to find an effective substance to corner a large number of ovipositing females to selective breeding sites for ease of control operation. This will reduce insecticidal consumption and will be cost effective. This study is aimed to evaluate the oviposition attractancy of aqueous infusion from a wood inhabiting fungus (Polyporus spp.) for vector mosquitoes both in the laboratory and under field conditions. METHODS: An aqueous infusion (10%) was prepared by soaking 10 g of fungal powder in 100 ml of chlorine-free tap water. The mixture was shaken thoroughly and filtered through Whatman No. 1 filter paper. The filtered infusion was tested for oviposition attractancy against vector mosquitoes both in the laboratory and under field conditions. RESULTS: The laboratory study on the dose-effect relationship indicated that at an optimum concentration of 4 ppm, maximum attractancy was observed. Water treated with aqueous fungal infusion (AFI) at 4 ppm received significantly more egg rafts/eggs of vector mosquitoes than other substrates like rearing water, natural breeding water and tap water. Trials conducted in the field showed that mud pots treated with AFI placed in both indoor and outdoor locations received significantly more Aedes aegypti eggs than the control. Similarly, treated pots placed in paddy fields attracted significantly more gravid Anopheles subpictus for oviposition than untreated pots. In contrast, the number of egg rafts of Culex quinquefasciatus laid in AFI treated pots was significantly less than in the control ones owing to strong natural olfactory factors associated with the breeding habitat. INTERPRETATION & CONCLUSION: The results indicated that there is scope for developing a trap incorporating this oviposition attractant along with insect growth regulator(s) (IGR) for surveillance and/or control of Ae. aegypti and other vector mosquitoes breeding in paddy fields. PMID- 11762203 TI - HLA antigen distribution in Jain population from Mumbai, Maharashtra, India. AB - BACKGROUND & OBJECTIVES: The Indian population is well known for its genetic diversity. Among the numerous endogamous communities, the Jain community from Mumbai is very restricted by custom, marriage and occupation. We present here the HLA antigen distribution of individuals belonging to this endogamous community. METHODS: A total of 161 healthy individuals of the Jain community working or studying in a hospital at Mumbai were selected randomly during 1985-1988. HLA class I and class II antigens were identified by using the standard National Institutes of Health (NIH) microlymphocytotoxicity assay. RESULTS: The phenotypic frequencies of HLA A1, A2, A9, A11, A24, B5, B35, B40, Cw4, DR2, DR3, DR4, DR5 and DR7 were increased while frequencies of HLA A10, A19, A26, A32, B7, B14, B16, B21, B22, B27, B37, Cw2, DR1 and DR9 were decreased when compared with other populations from, Maharashtra. The phenotype frequencies of HLA A26, A28, A30, B18, B40, B56, Cw3, Cw4, DR3, DR4 and DR5 were increased while the frequencies of HLA B7, B15, B16, B22, B37, Cw2, Cw6, DR1 and DR9 were decreased when compared with frequencies in other Indian populations. Two locus haplotype analyses revealed that A9-B5, B35-Cw4, DR2-DQ1 and DR7-DQ2 were significant haplotypes among the positive linkage disequilibrium haplotypes. Whereas A9-B35, B35-Cw1 and DR1-DQ2 were significant haplotypes among the negative linkage disequilibrium haplotypes. INTERPRETATION & CONCLUSION: The study revealed that the Jain population of Mumbai cannot be considered as a single panmictic population with reference to genetic characteristics, this may have a clinical relevance in unrelated donor selection for allogenic bone marrow transplantation in India. PMID- 11762204 TI - The V kappa III subgroup light chain proteins in AL amyloidosis & autoimmune diseases. AB - BACKGROUND & OBJECTIVES: Light chain associated amyloidosis (AL) is characterized by extracellular deposition of immunoglobulin light chain and its fragments. In vitro and in vivo studies have shown that some light chains are nonamyloidogenic and nonnephrotoxic, whereas others are potentially amyloidogenic. Some light chains are prone to be deposited as rheumatoid materials, and also as nodular amorphous aggregates (light chain deposition diseases). These findings suggest that specific sequence element(s) may control the various kinds of light chain associated diseases. In this study we tried to identify such sequence element(s). METHODS: Two Bence Jones proteins (BJPs), NIG93 and NIG2 of subgroup V kappa III, were characterized and compared with other members of the same subgroup whose sequences are available in the data base. RESULTS: Both NIG93 and NIG2 proteins had sequences characteristics of V kappa IIIa as distinguished from V kappa IIIb, subsubgroup proteins. They also contained several novel substitutions, such as Met-37, Leu-40, Val-58, and IIe-85 in NIG93, and Val-2, His-29, Arg-50, and Ile 72 in NIG2. The data accumulated at present indicate that all members of the V kappa IIIa subsubgroup are related to either AL amyloidosis or rheumatoid arthritis, whereas the V kappa IIIb proteins are related to autoimmune diseases. INTERPRETATION & CONCLUSION: These observations indicate that subgroup-specific residues might be critical for light chain pathogenesis, at least for the V kappa III proteins. Point mutations within these proteins may be another structural element controlling their conformation as well as their pathogenic aggregation. PMID- 11762205 TI - The 24th Annual Meeting of the Canadian College of Neuropsychopharmacology. Banff, Alberta, Canada, June 17-20, 2001. PMID- 11762208 TI - Circadian secretion of cortisol in bipolar disorder. AB - OBJECTIVE: To compare the 24-h cortisol secretion profiles of normal control subjects and patients with bipolar disorder who were in the depressive, manic and euthymic phases of the disorder. PARTICIPANTS: Eighteen patients, 25-62 years of age, in depressed (n = 5), manic (n = 5) or euthymic (n = 8) phase of bipolar disorder recruited through a psychiatric outpatient clinic, and 5 control subjects, 24-41 years of age, recruited through advertisement or word of mouth. OUTCOME MEASURES: Subjects were interviewed and symptom ratings were obtained using the Hamilton Depression Rating Scale, Beck Depression Inventory and Young Mania Scale. Blood collection began at 0800 and continued at hourly intervals for 24 h. Serum cortisol levels were assayed using a validated commercial radioimmunoassay kit. RESULTS: An analysis of variance of the area under the cortisol 24-h time-concentration curve (AUC) revealed a significant difference between the control group and patient groups (F = 3.69, p = 0.03). the mean AUCs of the patients in the depressed (263.4 micrograms/dL) and hypomanic (262.2 micrograms/dL) phases were beyond the 95% confidence interval for the controls (120.9-253.3 micrograms/dL). There were no significant group differences in cosinor acrophase and no significant effects of sex, education, age of illness onset, duration of illness or duration of mood state at time of testing on the cortisol measures. Pearson correlations between symptom rating scores and cortisol secretion variables were not significant. CONCLUSION: The increases in cortisol secretion in patients in both the depressed and manic phases of bipolar disorder suggest that cortisol level is probably not a state marker in bipolar disorder. PMID- 11762206 TI - How do the atypical antipsychotics work? AB - Understanding the action of atypical antipsychotics is useful in exploring the pathophysiology of schizophrenia and in synthesizing drugs that improve various domains of psychopathology without unwanted side effects. In animal models, atypical antipsychotic drugs appear to have a preferential action in the limbic dopaminergic system. Regionally specific action has been studied by measuring the amount of Fos protein produced in a particular brain region as a consequence of a drug's effects on the c-fos gene. Evidence suggests that the atypical and typical antipsychotic drug-induced increases in Fos levels in the nucleus accumbens are related to improvements in positive symptoms, whereas Fos increases in the prefrontal cortex, with the atypical antipsychotics only, correlate with negative symptom improvement. The extrapyramidal effects seen with typical antipsychotics are thought to be related to Fos increases in the striatonigral pathway. However, studies of Fos levels in specific brain regions reveal only the site of action, not the mode of action. The finding that atypicality is related to surmountable D2 dopamine receptor blocking provides another venue to define and explore atypical antipsychotic drug action. PMID- 11762209 TI - Prevalence of tics and Tourette syndrome in an inpatient adult psychiatry setting. AB - OBJECTIVE: Given the widely recognized genetic basis for Gilles de la Tourette syndrome (TS) and the suggestion that the putative TS gene(s) may be expressed as or associated with a variety of psychiatric illnesses, this study was undertaken to assess the prevalence of tics and TS in a psychiatric inpatient population. DESIGN: Cross-sectional study. SETTING AND PATIENTS: 200 consecutive adult patients who were admitted to the psychiatric wards of University College London Teaching Hospitals. OUTCOME MEASURES: TS and related behaviours, as assessed by the comprehensive semi-structured National Hospital Interview Schedule. RESULTS: None of the 200 patients had definite TS, but 2 were observed to have motor tics; 10 had a history of tics (present for less than a year), and 7 reported a family history of tics. Thus, 19 (9.5%) inpatients qualified for inclusion in a broadly defined TS diathesis. These rates are significantly lower than those reported in a similar community based epidemiological study of adolescents (p = 0.018). CONCLUSIONS: Our findings do not support the theory that TS and related behaviours are over-represented among adult inpatients with psychiatric illnesses. PMID- 11762211 TI - [The expression characteristics and their biological significance of epidermal growth factor and basic fibroblast growth factor in rat skins at different development stages]. AB - OBJECTIVE: To explore the localization and expression characteristics of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in rat skins at different development stages (embryonic, newborn, adult). METHODS: Skins from embryonic, newborn and adult rats were taken, and detected by immunohistochemical technique. RESULTS: Positive immunohistochemical signal of EGF could be found in skins from embryonic, newborn and adult rats, mainly in the cytoplasm of the epidermal cells, fibroblasts, hair follicle epithelial cells, and endothelial cells. With the increase in age, the expression amount of EGF was increased. The positive signal of bFGF could be found in skins of newborn and adult rats, while the signal of bFGF in skin of embryonic rats was negative. CONCLUSION: The results indicate that endogenous EGF plays important role in epidermal development in embryonic stage and wound healing in adult after injury. The negative expression of bFGF in skin of embryonic rat indicate that the absence of bFGF may be one of the reasons for the non-scar healing in embryonic stage. PMID- 11762210 TI - When should one stop cholinesterase inhibitors in patients with Alzheimer's disease? PMID- 11762212 TI - [Effect of subcutaneous tissue trimming on the survival skin area of avulsion skin flap]. AB - OBJECTIVE: To investigate the effect of subcutaneous tissue trimming on the survival skin area of avulsion skin flap. METHODS: Degloving injury was created in bilateral hind limbs of 7 pigs with avulsion injury machine, 4 cm x 10 cm avulsion skin flaps were elevated in degloving areas. Skin flaps in one side were replanted as control without any treatment. Subcutaneous tissue in the skin flaps of another side was partially excised and replanted by trimmed skin flaps. Survival skin flaps was calculated with computer at 7 days after operation. RESULTS: In the control group, the survival skin area was (40.41 +/- 9.23)%, while in the experimental group, the survival skin area was (60.90 +/- 15.26)%. There was significant difference between the two groups (P < 0.05). CONCLUSION: Trimming off subcutaneous tissue does improve the survival area of avulsion skin flap. PMID- 11762213 TI - [Repair of facial soft tissue defect using temporal flap pedicled with orbicularis oculi muscle]. AB - OBJECTIVE: To probe into the methods and effects of small soft tissue defect of facial area, nose and eyelid repaired by temporal island flap pedicled with orbicularis oculi muscle. METHODS: From 1994 to 1999, 12 cases with cicatricial ectropion of eyelid, scar in nose and facial area or facial mole were repaired by temporal flap pedicled with orbicularis oculi muscle. The maximal area of skin flap was 3 cm x 5 cm. RESULTS: All the skin flaps were survived after operation. Six cases were followed up from 6 months to 4 years, the results were satisfied. There were no secondary deformity or scar formation in the donor site. CONCLUSION: The blood supply of orbicularis oculi muscle is plentiful. It is a reliable method to repair of small facial tissue defect using temporal island flap pedicled with orbicularis oculi muscle. But in bigger facial soft tissue defect, it should be cautious. PMID- 11762207 TI - Animal models of schizophrenia: a critical review. AB - Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself. Differing theories as to the cause and progression of schizophrenia, as well as the heterogeneity of clinical symptoms, have made it difficult to develop a coherent framework suitable for animal modelling. However, a number of limited animal models have been developed to explore various causative theories and to test specific mechanistic hypotheses. Historically, these models have been based on the manipulation of neurotransmitter systems believed to be involved in schizophrenia. In recent years, the emphasis has shifted to targeting relevant brain regions in an attempt to explore potential etiologic hypotheses. The specific animal models developed within these frameworks are described in this review. Emphasis is placed on the critical evaluation of currently available models because these models help to shape the direction of future research. PMID- 11762214 TI - [Clinical application of the serial flap pedicled with posterior interosseous artery and its recurrent branch]. AB - OBJECTIVE: To explore a new surgical approach to repair skin and soft tissue defect of hands. METHODS: Based on the anatomical study of the origin, course, branch, distribution, and anastomosis of the posterior interosseous artery and its recurrent branches in 40 upper limbs of cadavers, the posterior forearm serial flap, pedicled with the posterior interosseous artery and its recurrent branches, was designed and applied clinically in 17 cases to repair the skin and soft tissue defect of hands from August 1998 to July 2000. The size of flaps ranged from 7 cm x 5 cm to 15 cm x 10 cm. All of the cases were followed up for 3 weeks to 6 months. RESULTS: The anatomy study showed that the posterior forearm serial flap had long vascular pedicle, suitable thickness and large skin area. The clinical application indicated that the flaps survived in 16 cases. But flap necrosis at the distal end, sized 2 cm x 3 cm, was observed in one case, in which the defect was repaired by delayed skin grafting, CONCLUSION: The posterior forearm serial flap pedicled with the posterior interosseous artery and its recurrent branch have the character of avoidance of sacrificing the major arteries of the extremity, longer vascular pedicle, larger area and suitable thickness. The posterior forearm serial flap is a safe and easily manipulated surgical approach to repair the skin and soft tissue defect of the hands, especially of the thumb, palm, and proximal part of the fingers. PMID- 11762215 TI - [Pedicle graft of intestine seromuscular layer and skin graft for repair of abdominal wall defect]. AB - OBJECTIVE: To explore an effective method to repair the abdominal wall defect. METHODS: From July 1996 to December 2000, 7 cases with abdominal wall defect were repaired by pedicle graft of intestine seromuscular layer and skin graft, among them, intestinal fistula caused by previous injury during operation in 4 cases, abdominal wall defect caused by infection after primary fistulization of colon tumor in 2 cases, abdominal wall invaded by intestinal tumor in 1 case. Exploratory laparotomy was performed under general anesthesia, the infective and edematous tissue around abdominal wall defect was gotten rid off, and the pathologic intestine was removed. A segment of intestine with mesentery was intercepted, and the intestine along the longitudinal axis offside mesentery was cutted, the mucous layer of intestine was scraped. The intestine seromuscular layer was sutured to the margin of abdominal wall defect, and grafted by intermediate split thickness skin. RESULTS: The abdominal wall wound in 6 cases were healed by first intention, but part of grafted skin was necrosed, and it was healed by second skin graft. No intestinal anastomotic leakage was observed in all cases. Followed up 1 to 2 years, there were no abdominal hernia or abdominal internal hernia. All the cases could normally defecate. The nutriture of all cases were improved remarkably. CONCLUSION: Pedicle graft of intestine seromuscular layer is a reliable method to repair abdominal wall defect with low regional tension, abundant blood supply and high successful rate. PMID- 11762216 TI - [The effectiveness of prolene patch in hernia prevention following harvesting rectus abdominis myocutaneous flap]. AB - OBJECTIVE: To investigate the effectiveness of polypropylene path (Prolene) in hernia prevention following harvesting of rectus abdominis is myocutaneous flap. METHODS: From November 1999 to October 2000, Prolene patches were applied in 26 cases to repair the anterior rectus sheath following harvesting free rectus abdominis myocutaneous flap. Data concerning each case included size of rectus flap, defect of rectus sheath, size of patch used, wound healing and complications. RESULTS: Prolene patch showed good biocompatibility with abdominal tissue. No foreign-body rejection occurred after operation. Seroma developed in 1 case, and was drained bedside without complication. All prolene patches healed well in the body during follow-up. Hernia formation and abdominal bulge were not observed. CONCLUSION: Prolene patch is a satisfactory material for repair of the anterior rectus sheath after harvesting free rectus abdominis myocutaneous flap. PMID- 11762217 TI - [Treatment of the wound on donor site after great toe-nail flap grafting]. AB - OBJECTIVE: To investigate the method of improving the vitality of skin graft on donor site of the great toe-nail skin flap. METHODS: From June 1982 to April 1998, 252 cases of the great toe-nail flaps with piece of phalangeal bone and 18 cases of the simple great toe-nail flap were repaired with thin skin graft and packed under proper pressure. The stitches were removed two weeks later in common situation. It should be postponed on split thickness or partial survival skin flap avoiding early mobilization. RESULTS: Sixty-six cases of skin graft were necrotic after operation. Among them, 38 cases needed second skin grafting and 28 cases were healed after changing dressing. The survival rate of skin grafting was obviously higher on phalangeal marrow surface than on periosteum of the naked phalange. Contracture of the skin graft after operation made the retained skin flap expanding from medial side to lateral side and covered the whole plantar surface of the great toe. CONCLUSION: The survival rate of the skin graft on donor foot is improved after adopting the improved measures on taking the flap from great toe and paying attention to skin graft planting and packing. Free flap grafting is advocated for repairing of the wound on donor area of the great toe nail flap. PMID- 11762218 TI - [Surgical repair of hypospadias with urethral burying and scrotal skin flap transplantation]. AB - OBJECTIVE: To investigate the surgical approach to repair hypospadias. METHODS: From 1992 to 2000, 42 cases with hypospadias accepted secondary urethroplasty after primary operation, which included urethral burying in penile skin, bladder mucosa and scrotal septal vascular pedicled flap urethroplasty, trans-scrotal skin flap covering the wounds with normal meatus urinarius. RESULTS: Only one, out of 42 cases, had early complication of urinary fistula in 7 days after urethroplasty, which was cured by scrotal septal vascular pedicled flap urethroplasty 3 months later and had no further complication. The others were all succeeded once for all, the successful rate was 97.6%. CONCLUSION: The surgical method to repair hypospadias by urethral burying and transscrotal skin flap technique is safe, reliable and recommendable for clinical use. PMID- 11762219 TI - [Use of heterogeneous acelluar dermal matrix and autologous overthin split thickness skin for repair of deep burn at articular sites]. AB - OBJECTIVE: To investigate the effect of heterogeneous (swine) acellular dermal matrix (s-ADM) and autologous overthin split-thickness skin (auto-OTS) composite grafting in repair of deep burns at articular sites. METHODS: From May 1999 to April 2000, 19 articular sites in 16 patients, including 14 males and 2 females, were treated. In all the 19 sites of deep burn, the total burn area varied from 2% to 48% and the full-thickness burn area varied from 1% to 35%. After the primary escharectomy (1 to 5 days later) and complete hemostasis, the s-ADM was utilized to cover the exposed articular sites and the auto-OTS was transferred on the surface of sutured s-ADM. The size of s-ADM applied to each patient varied from 25 cm2 to 150 cm2. Regular skin grafting was adopted elsewhere other than the articular site. The survival rate of all skin grafting was evaluated and pathological examination was performed. RESULTS: The survival rate of the composite skin was (90.80 +/- 18.34)%, which was obvious higher than the survival rate of contiguous granulosum skin grafting (P < 0.05) and almost the same with that of snip skin grafting(P > 0.05). The survived composite skin appeared as smooth and soft as normal skin, and the function of articular site almost recovered with neglectable hypertrophic scar. The pathological examination revealed that the normal cell grew into s-ADM with regularly arranged collagen fiber and neovascularization in the matrix. CONCLUSION: The combination of s-ADM and auto-OTS graft is cheap and effective method to cover wound and minimize hypertrophic scar. PMID- 11762220 TI - [Expression of alpha-smooth muscle actin in scar fibroblasts in vitro]. AB - OBJECTIVE: To explore the expression of alpha-smooth muscle actin (alpha-SMA) induced by transforming growth factor beta 1 (TGF-beta 1). METHODS: Five samples of hypertrophic scars and three samples of normal mature scars were collected as the experimental and control groups respectively. The fibroblasts were isolated from scars, and cultured in 2-dimension or 3-dimension culture system. The immunohistochemical staining method of LSAB were used to investigate the expression of alpha-SMA in fibroblasts in the different concentration of TGF-beta 1. RESULTS: The expression of alpha-SMA in 3-dimension culture system were markedly lower than those in 2-dimension culture system with respect to the fibroblasts in the experimental group. The expression of alpha-SMA in fibroblasts were different in response to various TGF-beta 1 concentration, it was more effective at the concentration of 5 ng/ml. The expression of alpha-SMA in the fibroblasts from hypertrophic scars seemed to be more sensitive to TGF-beta 1 compared to that of the normal mature scars. CONCLUSION: There are concentration dependent in the expression of alpha-SMA induced by TGF-beta 1 in scar fibroblasts in vitro. The biological characteristics of the fibroblasts from hypertrophic scars and normal mature scars and their sensitivity to the inducement of TGF-beta 1 were different. The inducement of TGF-beta 1 may be depressed by extracellular matrix components and that may decrease the expression of alpha-SMA. PMID- 11762222 TI - [Allogeneic humeral shaft transplantation with vascular anastomosis: twenty years follow-up]. AB - OBJECTIVE: To sum up the clinical results of allogeneic humeral transplantation with vascular anastomosis, and evaluate the clinical significance. METHODS: From September to November 1979, 1 case with humeral shaft defect of 10 cm in length and 2 cases with tibia shaft defect of 12 cm in length were repaired by allogeneic humeral transplantation with vascular anastomosis. Azathiopurine and prednisone were applied for 3 months postoperatively. All cases were followed up for 20 years. RESULTS: Case 1 recovered well with good bone union and reconstruction after operation, and could work normally. In case 2, five chronic rejections were occurred during 3 years after operation, and recovered after treatment, the allograft bone was fractured after 2 years of operation, and unioned by autogeneous iliac bone transplantation. In case 3, the distal part of allograft bone was fractured after 46 months, and unioned by autogeneous iliac bone transplantation. The middle part of allograft bone was non-unioned after 20 years follow-up in case 3, but the patient could still work normally. CONCLUSION: The clinical results of allogeneic long bone transplantation can be improved by rational tissue matching test, application of effective immunosuppressive drugs in a certain period according to the principles of modern transplantation immunology. PMID- 11762221 TI - [Experimental study of Bcl-2 and Fas gene expression in fibroblast of scar]. AB - OBJECTIVE: To explore the effect of Fas/Apo-1 and Bcl-2 gene expression on mechanism of scar formation. METHODS: Immunohistochemical method was applied to defect the expression of Fas and Bcl-2 protein in fibroblasts from 10 cases with normal skin, 10 cases with hypertrophic scar and 10 cases with keloid. RESULTS: The positive expression rate of Bcl-2 protein in keloid was 83.2%, significantly higher than that in hypertrophic scar (38.6%), (P < 0.01), and the positive expression rate in hypertrophic scar and keloid was higher than that in normal skin (6.78%), (P < 0.01). But the positive expression rate of Fas/Apo-1 protein was 78.4% in normal skin 80.4% in hypertrophic scar, 84.4% in keloid respectively, which showed no significant difference among them (P > 0.05). CONCLUSION: Bcl-2 gene but Fas gene may take part in the formation of pathologic scar. PMID- 11762223 TI - [Repair and reconstruction of radial nerve injury]. AB - OBJECTIVE: To investigate the reparative method and effect of radial nerve injury. METHODS: From 1990 to 2000, 50 cases with radial nerve injuries were adopted in this study. Among them, there were 38 males and 12 females, aged from 5 to 65 years. For the 50 cases, there were 28 cases with complete nerve rupture, 3 cases with incomplete nerve rupture, 10 cases with compressive injury, 5 cases with contusion injury and 4 cases with defect and irreversible injury. All the patients were treated with radial nerve exploration in 1 hour to 6 months after injury. 31 cases were treated with nerve anastomosis, 10 cases with nerve lytic operation, 4 cases with tendon transfer and 5 cases with palliative treatment. RESULTS: All the cases were followed up 3 months to 10 years. The curative effect was assessed according to Highest grade method. There were excellent and good results in 46 cases, moderate results in 4 cases. CONCLUSION: It is necessary to explore and repair the radial nerve injury immediately after the diagnosis being confirmed. If the function of radial nerve could not recover in 6 months, tendon transfer should be carried out to reconstruct the extension of elbow, thumb and fingers. PMID- 11762224 TI - [Experimental study on compound of xenogenic inorganic bone and auto-marrow encapsuled by pedicled muscular flap]. AB - OBJECTIVE: To explore the possibility of prefabricate a vascularized artificial bone-muscular flap, a compound of xenogenic inorganic bone and auto-marrow, with capability of osteogenesis. METHODS: Twelve 6-month New Zealand rabbits were divided into two groups, compound of xenogenic inorganic bone and auto-marrow implanted into the muscle near to radia and ulna of left forefoot as experimental group. Simple xenogenic inorganic bone implanted into the same site of right side as control group. After 2, 8, 12 weeks, x-ray examination, gross evaluation and histological observation were carried out. RESULTS: X-ray film showed that the implant had a cancellus-like density, and no variance with time. Since 2 weeks after implantation, gross observation showed a complete fusion formed between the implant and the host muscular tissue, with obvious blood vessels on the surface of the muscular flap in which the compound was encapsulated. No necrosis was observed in the following 30 minutes after the compound was dissected from its surrounding tissues. The histological investigation showed a contact connection between implant and its surroundings. In the experimental group, no new bone formed but in-growth of blood vessels was observed at the end of the 2nd week, and a little new bone formed along the edge of xenogenic inorganic bone at the end of the 8th week, while at the end of 12th week, more new bone formed in the compound with osteocytes in bone lacuna, plenty blood vessels in bone matrix, and lots of osteoblasts surrounded by un-differentiated mesenchymal cells at the fringe of the new bone. While in the control group, there were only loose connective tissue with blood vessels grew into xenogenic inorganic bone with no new bone formation until 12 weeks. CONCLUSION: The compound of xenogenic inorganic bone and auto-marrow can promote the formation of vascularized myo-bone flap with new bone formation. PMID- 11762225 TI - [Effect of costal perichondrium on regeneration and remodeling of costal neocartilage]. AB - OBJECTIVE: To provide experimental basis for improving the curative effect of pectus excavatum. METHODS: Twelve rabbits were adopted in this experiment. After the bilateral second and third costal cartilages of the rabbits were resected subperichondrially, their right second and third costal perichondriums were damaged intentionally. Then, the bilateral third costal perichondriums were stitched into a tube-like structure and the second ones were left opened. After 2, 4, 6 of operation, the bilateral second and third neocartilages were measured for their width, and histological character were observed under microscope. RESULTS: 1. After 2, 4, 6 months of operation, the average width of the bilateral second neocartilages were significantly greater than the preoperative ones. 2. 4 and 6 months after operations, there was no significant difference in the average width of the bilateral third neocartilages and the preoperative ones. 3. The amount, distribution of costal neocartilage cells and the arrangement of costal neocartilage matrix within the left second and third costal cartilages were better than the right under the light microscope. 4. The left third costal neocartilage was regenerated and remodeled better than all the others. CONCLUSION: The integrality of costal perichondrium is in favor of the regeneration of costal cartilage, and the sleeve stitch of costal perichondrium facilitates the remodeling of costal neocartilage. PMID- 11762226 TI - [Anterior lumbar interbody fusion of canine with allograft cortical ring plus autogenous cancellus]. AB - OBJECTIVE: To prove the biological characteristics of spinal intervertebral fusion with allograft cortical ring plus autogenous cancellus from iliac bone (called as composite ring). METHODS: Eight hybrid dogs were adopted in the study. The composite ring and autogenous tri-cortical blocks were implanted into the intervertebral space of dogs respectively. The intervertebral discs were removed before implantation. The fusion segments were evaluated by x-ray, histological examinations at 1, 2, 4 and 6 months after operation to compare the healing status of two implants. RESULTS: The X-ray film and histological examination showed the lumbar interbody was fused after 4 months of operation in composite ring group, while the autogenous iliac bone blocks fused with peripheral bone tissue after 6 months of operation. Composite ring healed more quickly and completely, showed different osteogenesis behavior compared with that of massive allografts. CONCLUSION: Composite ring can promote the fusion of intervertebral body and can be used as a potential material for spinal surgery. PMID- 11762227 TI - [Replantation of segmental destructive amputation of multiple fingers]. AB - OBJECTIVE: To discuss the indication of replantation of destructive amputation of multiple fingers for improvement of the function of injured fingers. METHODS: From February 1996 to August 1999, 23 amputated fingers in 8 cases were shortened and replanted. The crushed digital bones were fixed by Kirschner wires, flexor tendons repaired by Kessler suture technique, and digital extensor tendons repaired by mattress suture. The arteries and veins were anastomosed in each finger at the ratio of 1 to 2 or 2 to 3. The defect of blood vessels was repaired by free graft of autologous veins in 5 fingers. All of the cases were followed up for 10 to 18 months, and clinical evaluation was performed. RESULTS: All replanted fingers survived in the 8 cases, with good sensation, two point discrimination of 6 to 12 mm, and satisfied function, such as pinching, grasping and hooking. The fingers were shortened for 2.6 cm in average, ranging from 2.2 cm to 4.0 cm. CONCLUSION: Multiple digits replantation by shortening fingers is beneficial to functional restoration of segmental destructive fingers. PMID- 11762229 TI - [Experimental study on isolated testes with ischemia/reperfusion injury]. AB - OBJECTIVE: To investigate the injury on isolated testes induced by ischemia/reperfusion(I/R), and the protective effect of Yisheng injection on the injury. METHODS: Twenty-six isolated cadaver testes contributed by 13 persons were preserved with 4 degrees C 250 ml hypertonic citrate alloxuric (HCA) solution and then reperfused with 37 degrees C 500 ml HCA. Solution of experimental group contained 500 micrograms/ml Yisheng injection. In simple cold preservation test, involving in 8 experimental and 8 control testes, a series of time points (6, 12, 18, 24, 36, 48, 60, 72 hours) were set to harvest. 10 testes (1 testis respectively on 6, 12, 18, 24 and 36 hours in experimental and control groups) were reperfused with 37 degrees C HCA for 6 and 12 hours. Histological and histochemical changes were observed. RESULTS: In the experimental testes, 4 degrees C cold preservation in 24 hours could not induce obvious pathologic changes. After 24 hours, changes such as swelling, vacuolar degeneration or detachment of endothelial cells (ECs), separation between basement membrane and seminiferous epithelium, mal-alignment of spermatogenous cell and edema of mesenchyme could be observed. In the testes preserved for 12 hours, the activity of lactic dehydrogenase(LDH) and succinic dehydrogenase (SDH) increased, then fallen after 24 hours. The activity of Nitric oxide synthetase(NOS) decreased after 18 hours. All changes were more obvious after following 37 degrees C reperfusion. In the control testes, swelling and vacuolar degeneration of ECs occurred on 12 hours cold preservation, and injury was worse along with the prolongation of cold preservation time. Pathologic changes of ECs, seminiferous epithelium and mesenchyme were serious after 37 degrees C reperfusion. CONCLUSION: 4 degrees C cold preservation in 24 hours can only cause mild ECs' injury, and obvious abnormal testes' histological profile can be observed beyond 24 hours. 37 degrees C reperfusion will make injury worse. Yisheng injection can keep isolated testes histologic structure well in 24 hours cold preservation, and it has protective effect on I/R injury. PMID- 11762228 TI - [Experimental study of tissue engineered bone with coralline hydroxyapatite as scaffolds]. AB - OBJECTIVE: To investigate the feasibility of coralline hydroxyapatite (CHA) as scaffolds in bone tissue engineering. METHODS: The bone marrow stromal cells from 4-month New Zealand rabbits were harvested and cultured in vitro. After multiplied, dexamethasone was used to promote the osteoblastic phenotype of the cells. The cells were harvested and then seeded into CHA. By means of tissue engineering technique, osteoblastic cells/CHA complex were formed. The complex were implanted subcutaneously in nude mice. The CHA alone was implanted as control. Bone regeneration was assessed 6, 8 weeks after implantation by histological and roentgenographic analysis. RESULTS: After six weeks of implantation, x-ray film showed high-density signal, osteoid tissue formed under histological examination. Large amount of new bone were formed and connected to trabecularism 8 weeks after implantation in the experimental group. While in the control group, there were no new bone formation, but amount of fiber tissue grew into the pore of CHA 8 weeks after implantation. CONCLUSION: CHA may be used as a good scaffold material for bone tissue engineering. PMID- 11762230 TI - [Psychology during the process of human hand allograft]. AB - OBJECTIVE: To study the psychology and its management during the process of hand allograft. METHODS: One psychologist participated through the whole process of the present hand allograft. 12 potential candidates of hand transplant were interviewed during the selection of patients to evaluate the state of psychiatry and their abilities to manage stressors like cooperation with medical workers and medical interventions, waiting for donors, adaptation to a new hand and post operation depression. The psychological state of 11 patients were believed to be able to receive hand transplant, and they are further prepared psychologically by the psychologist while waiting for a donor. Two lucky candidates were decided by tissue typing and received hand allograft simultaneously. After the operation, the two patients psychotherapy assisted with effective analgesia, supporting from family and environmental improvement. RESULTS: One out of 12 patients was found not suitable for the transplantation because of psychiatric problem. One week postoperation, the 2 patients were anxious, lack of patience, and horrified at seeing the long-expected grafted hand. After 1 week of treatments and adapation the patients managed to settle with the new hand, and accepted the hand as a whole 1 month postoperation. With the recovery of the hand sensation and motion 4 to 5 months postoperation, the patients held the hand as his own. CONCLUSION: Psychologists are required in the hand transplantation team during the pre transplant selection of patients and post-transplant rehabilitation. PMID- 11762231 TI - [The current condition and research progress of normal wound repair and "un controlled" wound repair]. AB - OBJECTIVE: To describe the concept of "un-controlled wound repair" and review its current progress in basic research and clinical treatment. METHODS: The literature review and comprehensive analysis methods were used in this study. RESULTS: The results showed that the normal wound repair and "un-controlled" wound repair had made big progress in cellular, molecular and genetic levels in recent years and these progresses had enhanced the treatment progress in clinic. CONCLUSION: All data indicate that the wound repair is made a big progress both in basic and clinic fields. New high techniques, such as clone, biochip and stem cell and their use will promote the deep study of "un-controlled" wound repair. PMID- 11762232 TI - Detection of sinusoidal gratings by pattern-specific detectors: further evidence for the correlation principle in human vision. AB - The detection of compound sinusoidal gratings of various spatial frequency separations and four different grating sizes has been studied using the summation to-threshold paradigm. Contrast interrelation functions have been measured and spatial frequency tuning estimates, based on the slope of the contrast interrelation function at two definite points, were derived using the "negative gradient technique" proposed by Logvinenko [Logvinenko (1995) Biol Cybern 73: 547 552]. It is shown that compound grating detection can be modelled by assuming pattern-specific sensory mechanisms for each of the spatial frequency components, which adapt to the periodicity and the size of the stimulus but not to its envelope function. Further, it is shown that relative sensitivity for a given spatial frequency separation can be predicted with good accuracy by the correlation of the grating components used for superposition. It is suggested that the most plausible implementation of the pattern correlation principle in human grating detection is the "grating cell" model. PMID- 11762233 TI - Conditional transitions in gaze dynamics: role of vestibular nuclei in eye-only and eye/head gaze behaviors. AB - The gaze control system governs distinct gaze behaviors, including visual fixation and gaze reorientations. Transitions between these gaze behaviors are frequent and smooth in healthy individuals. This study models these gaze-behavior transitions for different numbers of gaze degrees of freedom. Eye/head gaze behaviors have twice the number of degrees of freedom as eye-only gaze behaviors. Each gaze behavior is observable in the system dynamics and is correlated with neuronal behaviors in several, coordinated neural centers, including the vestibular nuclei. The coordination among the neural centers establishes a sensorimotor state which maintains each gaze behavior. This study develops a mathematical framework for synthesizing the coordination among neural centers in gaze sensorimotor states and focuses on the role of vestibular nuclei neurons in gaze sensorimotor state transitions. PMID- 11762234 TI - Learning the dynamics of reaching movements results in the modification of arm impedance and long-latency perturbation responses. AB - Some characteristics of arm movements that humans exhibit during learning the dynamics of reaching are consistent with a theoretical framework where training results in motor commands that are gradually modified to predict and compensate for novel forces that may act on the hand. As a first approximation, the motor control system behaves as an adapting controller that learns an internal model of the dynamics of the task. It approximates inverse dynamics and predicts motor commands that are appropriate for a desired limb trajectory. However, we had previously noted that subtle motion characteristics observed during changes in task dynamics challenged this simple model and raised the possibility that adaptation also involved sensory-motor feedback pathways. These pathways reacted to sensory feedback during the course of the movement. Here we hypothesize that adaptation to dynamics might also involve a modification of how the CNS responds to sensory feedback. We tested this through experiments that quantified how the motor system's response to errors during voluntary movements changed as it adapted to dynamics of a force field. We describe a nonlinear approach that approximates the impedance of the arm, i.e., force response as a function of arm displacement trajectory. We observe that after adaptation, the impedance function changes in a way that closely matches and counters the effect of the force field. This is particularly prominent in the long-latency (> 100 ms) component of response to perturbations. Therefore, it appears that practice not only modifies the internal model with which the brain generates motor commands that initiate a movement, but also the internal model with which sensory feedback is integrated with the ongoing descending commands in order to respond to error during the movement. PMID- 11762235 TI - Fly-like visuomotor responses of a robot using aVLSI motion-sensitive chips. AB - We explore the use of continuous-time analog very-large-scale-integrated (aVLSI) neuromorphic visual preprocessors together with a robotic platform in generating bio-inspired behaviors. Both the aVLSI motion sensors and the robot behaviors described in this work are inspired by the motion computation in the fly visual system and two different fly behaviors. In most robotic systems, the visual information comes from serially scanned imagers. This restricts the form of computation of the visual image and slows down the input rate to the controller system of the robot, hence increasing the reaction time of the robot. These aVLSI neuromorphic sensors reduce the computational load and power consumption of the robot, thus making it possible to explore continuous-time visuomotor control systems that react in real-time to the environment. The motion sensor provides two outputs: one for the preferred direction and the other for the null direction. These motion outputs are created from the aggregation of six elementary motion detectors that implement a variant of Reichardt's correlation algorithm. The four analog continuous-time outputs from the motion chips go to the control system on the robot which generates a mixture of two behaviors- course stabilization and fixation--from the outputs of these sensors. Since there are only four outputs, the amount of information transmitted to the controller is reduced (as compared to using a CCD sensor), and the reaction time of the robot is greatly decreased. In this work, the robot samples the motion sensors every 3.3 ms during the behavioral experiments. PMID- 11762236 TI - A normal ocular motor system model that simulates the dual-mode fast phases of latent/manifest latent nystagmus. AB - The fast phases of latent/manifest latent nystagmus (LMLN) may either cause the target image to fall within (foveating) or outside (defoveating) the foveal area. We previously verified that both types are generated by the same mechanism as voluntary saccades and propose a hypothetical, dual-mode mechanism (computer model) for LMLN that utilizes normal ocular-motor control functions. Fixation data recorded during the past 30 years from 97 subjects with LMLN using both infrared and magnetic search coil oculography were used as a basis for our simulations. The MATLAB/Simulink software was used to construct a robust, modular, ocular motor system model, capable of simulating LMLN. Fast-phase amplitude versus both peak velocity and duration of simulated saccades were equivalent to those of saccades in normal subjects. Based on our LMLN studies, we constructed a hypothetical model in which the slow-phase velocity acted to trigger the change between foveating and defoveating LMLN fast phases. Foveating fast phases were generated during lower slow-phase velocities whereas defoveating fast phases occurred during higher slow-phase velocities. The bidirectional model simulated Alexander's law behavior under all viewing and fixation conditions. Our ocular-motor model accurately simulates LMLN patient ocular motility data and provides a hypothetical explanation for the conditions that result in both foveating and defoveating fast phases. As is the case for normal physiological saccades, the position error determined the saccadic amplitudes for foveating fast phases. However, the final slow-phase velocity determined the amplitudes of defoveating fast phases. In addition, we suggest that individuals with LMLN use their fixation subsystem to further decrease the slow-phase velocity as the target image approaches the foveal center. PMID- 11762237 TI - [Radiological management in emergency and trauma medicine]. PMID- 11762238 TI - [Stroke unit: requirements for diagnostic imaging and interventions]. AB - Stroke Units are specialised centers of expertise with the aim to optimize acute therapy of stroke. More specifically, the aims are (a) to reduce the area of brain infarction, (b) to prevent or appropriately react to complications, (c) to ensure an optimal strategy of secondary stroke prevention after having clarified etiopathogenesis, and (d) to establish a basis for subsequent rehabilitation. Stroke Units should collaborate for the evaluation and development of new diagnostic and therapeutic means. Patients' medical history, their clinical presentation and brain imaging create the basis for therapeutical decisions. The value of interventional therapy is presently evaluated for acute stroke therapy (e.g. intra-arterial thrombolysis) and secondary stroke prevention (Stent protected angioplasty of carotid stenosis). PMID- 11762239 TI - [Cerebrovascular emergency in neuroradiology]. AB - Common causes to consultate a neuroradiologist in case of emergencies are trauma, brain infarction, or intracranial bleeding. Patients with brain infarction need a rapid assessment of the potentially nonnecrotic area within the ischaemic lesion. If haemorrhage, mostly occurring in the form of subarachnoid bleeding, is suspected, the source of bleeding has to be detected. With cranial computed tomography (CT) a thorough evaluation and staging of ischaemic stroke is possible with respect to thrombolysis. To detect irreversible damage of brain tissue, a combined perfusion-diffusion MRI should be performed. PMID- 11762240 TI - [Acute head trauma: diagnostic imaging]. AB - Computed tomography (CT) ist the primary modality of choice for imaging patients with acute head trauma. Lesions of the soft tissues and of the bones can be assessed more precisely than with other imaging modalities. With magnetic resonance imaging (MRI) additional information may be gained especially in subacute and chronic posttraumatic conditions. Urgent indication to perform a CT examination depends on the patient's history and on the mechanism of trauma. Image interpretation has been performed in the context of typical pathologic effects of trauma and with respect to potential therapy. PMID- 11762241 TI - [Spinal injuries--diagnostic imaging]. AB - Spinal trauma requires a prompt and detailed diagnosis for estimating the prognosis and installing proper therapy. Conventional radiograms are the first imaging modality in most cases. In the cervical and the lumbar spine, a CT has to be performed in patients with polytrauma and a higher risk of complications or with signs of instability. Especially for imaging the cervicocranium, multiplanar reformations in sagittal and coronal planes are necessary. For fractures of the thoracic spine, MR imaging is superior to CT because of the better detection of associated neurologic complications. PMID- 11762242 TI - [Overuse and trauma in sports--clinical symptoms in the context of modern imaging techniques]. AB - New insights in the fields of pathology and diagnostic radiology of sports injuries show that the borders between overuse syndromes and trauma are blurred. Techniques of diagnostic imaging are increasingly important for an objective documentation of morphologic changes of the musculoskeletal system. Typical sports-related syndromes exist and their clinical diagnosis is not always easy because pain cannot be located exactly. PMID- 11762243 TI - [Tendon overuse syndrome: imaging diagnosis]. AB - Injuries of muscles and tendons occur commonly during various sporting activities and in most cases the athletes feel such an accident to be sudden and unavoidable. The rupture of a tendon, however, has to be considered in many cases as the final stage of a long-standing progressive degeneration of collagen fibers. This process can be described as "tendon overuse syndrome (TOS)". Diagnostic imaging modalities, especially sonography and MRI, are suitable to detect and analyse the different stages of this syndrome and the degree of morphological abnormalities. The first stage is painful functional derangement, followed by tendovaginitis, peritendinitis, or bursitis. The third stage is tendinosis resulting from biomechanical or ischaemic injury of tendon fibers which may eventually be followed by partial or complete rupture. Regional or individual specifications of these four stages may occur at anatomically predisposing sites, so-called critical zones, or during periods of specific proneness, the vulnerable phases. PMID- 11762244 TI - [Trauma of the bones of the hand and wrist]. AB - Fractures of the distal radius are common counting for 17 percent of all fractures. With conventional radiography they can be classified readily. Magnetic resonance imaging (MRI) is a suitable technique for the detection of occult forms of fractures and of associated soft tissue injuries. In the wrist, fractures are 10 times less common than in the distal radius, with the scaphoid bone to be involved most commonly. Indications for computed tomography (CT) are complex fractures, occult fractures, or dislocations. MRI should be performed to evaluate the soft tissues, to detect occult fractures, or to analyse osteochondral lesions. Indications for arthrography are injuries of the ligaments or of the joint capsule. Fractures and dislocations of the metacarpal, and the phalangeal bones are the most common fractures of the skeletal system. Conventional radiography is the primary imaging technique, followed by sonography and MRI to detect injuries of the ligaments and tendons. PMID- 11762245 TI - [Trauma of the knee joint--radiological diagnosis]. AB - The knee, the largest joint in the human body, is composed of the distal femur, the proximal tibia, the patella, and a complex arrangement of ligaments and menisci. This joint is particularly vulnerable because of its anatomic, functional, and mechanical characteristics. Depending on the severity and the specific mechanism of the trauma, injuries of soft tissue structures or bony elements or even a combination of both may be present. In case of severe pain caused by traumatic events clinical tests may be insufficient for exact diagnosis and radiological examinations are mandatory for an effective planing of the therapeutic management. PMID- 11762246 TI - [Radiological diagnosis of adult respiratory distress syndrome (ARDS)]. AB - The bedside chest radiograph represents the imaging modality of choice for diagnosis and monitoring of adult respiratory distress syndrome (ARDS). Imaging findings are strongly influenced by means of mechanical ventilation therapy. The chest radiograph is relatively insensitive and not specific for the diagnosis of complications such as pneumonia or interstitial emphysema. Computed tomography (CT) is suitable for quantitative assessment of lung compartments with respect to the degree of aeration and to tissue density values. With CT, the understanding of the underlying pathophysiology and the effects of ventilation therapy (PEEP) could be improved. The role of CT in the clinical routine is still limited due to the high risk to transport patients with ARDS. PMID- 11762247 TI - ["Tubes and lines" in thoracic radiography: malpositioning and complications]. AB - Chest radiography is essential to evaluate the placement and position of tubes and lines in patients treated in intensive care units, such as central venous and arterial catheters, endotracheal and nasogastric tubes, thorax drains, cardiac pacemakers and defibrillators. Radiologic findings with respect to normal positioning, wrong positioning, and complications are described and illustrated. PMID- 11762248 TI - [Diagnostic imaging of the acute abdomen]. AB - An acute abdomen may result from various diseases, with appendicitis, cholecystitis, pancreatitis, and obstruction of the small and the large bowel as the leading causes. The quality of diagnostic imaging has been improved within the last years especially by recent developments of cross-sectional imaging modalities. Sonography is an efficient modality for detecting cholecystitis and appendicitis. Spiral computed tomography is the modality of choice in case of suspected bowel obstruction or pancreatitis. PMID- 11762249 TI - [Diagnosis of aortic emergency]. AB - The CT angiography is the diagnostic method of choice in patients with aortic emergencies. It allows for reliable evaluation of aortic dissection, aortic rupture as well postoperative and post-interventional complications. It can be performed rapidly with the option of continuous monitoring of the patient. Transesophageal echocardiography is an alternative primary diagnostic method in patients with aortic dissections. MRI does not play a role due to the limited possibilities for patient monitoring. Only in patients with limited renal function MRI may be employed instead of CT as primary diagnostic modality. PMID- 11762250 TI - [Acute peripheral arterial ischemia: diagnosis and interventional therapy]. AB - Acute peripheral arterial ischaemia is characterized by a rapidly developing perfusion deficiency with potential necrosis of the involved extremity. In more than 90% an embolic or thromboembolic etiology is present. Differential diagnosis includes all other vascular disease entities. Digital subtraction angiography is the radiological modality of choice for diagnosis and interventional therapy. Prior to a planned local fibrinolytic therapy potential contraindications have to be excluded. PMID- 11762251 TI - ["Women's imaging": an integral diagnostic concept]. PMID- 11762252 TI - [Breast cancer: figures and facts]. AB - The diagnosis and therapy of breast cancer has been improved and individualized to a great extend during the past two decades. Large randomised trials guide our discussions and new results are integrated continuously into the concept of breast cancer diagnosis and treatment. The new achievements are an increased early detection of breast cancer, a reduction in invasive procedures for diagnosis and operative treatment and an improvement of reconstructive oncoplastic-procedures. Chemo- and hormonal therapy have increased the survival rate and have improved quality of live in advanced disease. The follow-up of patients with breast cancer has to be aimed on regular personal contact, mammography, and gynaecologic follow-up. Other laboratory parameters and imaging techniques have to be reduced and confined for patients with anamnestic or clinical evidence of tumour progression. PMID- 11762253 TI - [Conventional or digital mammography]. AB - Digital techniques have been applied in many fields of diagnostic radiology, but they were not accepted in mammography. The technological base of direct digital mammography was the development of CCD-chips. Clinical experiences with this system are promising and may lead to replacement of conventional techniques in the future. With intraindividual correlation studies it was shown that microcalcifications were detected better than with conventional techniques. Patients' dose is equal with both system and the reporting time could be reduced. Moreover, digital mammography is important for the use of software programmes of computer assisted diagnosis (CAD). PMID- 11762254 TI - [Quality assurance of mammographic devices]. AB - An account of the technical features of mammographic devices as a consequence of the radiological requirements for imaging the breast is given. For quality assurance of these features specific test procedures have been established which at least since the introduction of the MED-directive 97/43 of CEC have to be applied. A concise summary of these protocols is given. PMID- 11762256 TI - [Differential diagnosis of acute and chronic pelvic pain in women]. AB - Acute and chronic forms of pelvic pain are symptoms of various gynaecological entities with a difficult clinical differential diagnosis. Acute pains are generally intensive attacks with a sudden onset, rapid progression, and normally short duration. Chronic pelvic pain is a continuous non-cyclic condition. Transvaginal sonography is an efficient tool to document morphologic abnormalities. Other imaging modalities, especially magnetic resonance imaging (MRI) and computed tomography (CT) are valuable to differentiate gynaecological from other abdominal causes of pelvic pain. PMID- 11762255 TI - [Urological and nephrological emergency--value of diagnostic imaging]. AB - Many diseases of the kidneys and the urinary tract may develop to urinary emergencies. A prompt evaluation of these critical situations is of utmost importance concerning therapeutic consequences, and implicates a considerable challenge for the radiologist. The use of the appropriate imaging method allows rapid diagnosis, and thus enables optimal therapeutic management. In this article we describe the most important urinary emergencies: urolithiasis, hydronephrosis, acute renal infection, acute obstruction, testicular torsion, complications after renal transplantation, and urinary trauma. Aetiology and pathogenesis of the specific entities are described as well as the use of the adequate imaging method. In addition, especially for CT examinations precise imaging techniques are reported. Complications and differential diagnosis of the specific emergencies are mentioned. PMID- 11762257 TI - [Diagnostic imaging in gynecological emergencies]. AB - A wide spectrum of differential diagnosis exists in case of gynaecological emergencies which also includes gastrointestinal and urologic diseases. Radiologic imaging primarily bases on sonography, computed tomography and magnetic resonance imaging are used for subsequent evaluation. The detailed algorithm is oriented on clinical symptoms and signs. The most important signs are left and right lower quadrant abdominal pain, vaginal bleeding, and sudden onset of pain in the breast. PMID- 11762258 TI - [Sex differences in joint diseases: pathophysiological basis]. AB - Gender affects the susceptibility to many joint diseases, in particular autoimmune rheumatic disorders; women have an increased risk of rheumatoid arthritis, systemic lupus erythematosus or Sjogren's syndrome. In rheumatoid arthritis alterations of sex hormone levels such as androgen deficiency or prolactin excess might, at least in part, explain the excess incidence in women. Osteoarthritis of the hand and the knee as well as generalized osteoarthritis is more frequent in women than in men. Nevertheless, until now there is no explanation for the increased incidence of osteoarthritis in women. PMID- 11762259 TI - [Radiologic imaging of degenerative and inflammatory joint diseases in women]. AB - Pain in joints and other structures of the musculoskeletal system is a common complaint in women. It may occur as functional pain, in many cases as inflammatory episode of arthrosis or of metabolic joint disease, sometimes as early manifestation of rheumatoid disease. With conventional radiography, high resolution sonography, and MR imaging it is possible to classify many of these clinical syndromes. A semiquantitative assessment of inflammatory activity can be made by analysing the degree of joint effusion, the thickness of the synovium and the extent of hypervascularisation. PMID- 11762260 TI - [Temporomandibular joint pain: radiological diagnosis]. AB - Pain in the temporomandibular joint is often the result of internal derangement, other causes are traumatic, functional or inflammatory processes. Conventional radiography is indicated in case of suspected trauma or for specialised preoperative measurements to plan the treatment of various facial dysplasias. MRI and CT should be used in the context with the results of clinical investigation and of axiography to differentiate the various functional and morphological abnormalities of this joint. PMID- 11762261 TI - Analysis of pharmacoeconomics of sedation and analgesia. AB - Intravenous sedation and analgesia are cornerstones of the pharmacologic management of the critically ill, mechanically ventilated adult patient. No conclusive evidence exists to support any single optimal sedative or analgesic regimen in this heterogeneous population. The role of cost effectiveness in the process of selecting a regimen is explored with a review of the literature, followed by proposed cost-effectiveness models and recommendations for the clinical practitioner. PMID- 11762262 TI - Commentary. Balancing sedation and analgesia in the critically ill. AB - The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized. PMID- 11762263 TI - Anxiety, delirium, and pain in the intensive care unit. AB - Anxiety, agitation, delirium, and pain are common findings in the ICU. These unhealthy states may lead to increased irritability, discomfort, hypertension, tachycardia, cardiac ischemia, harmful motor activity, and psychologic disquiet for the patient. The appropriate treatment of these conditions may lead to decreased morbidity and mortality in the critically ill patient. Unfortunately, the management of anxiety, agitation, delirium, and pain in the intensive care unit is not ideal. Many patients interviewed after an ICU stay rate their pain control as poor and their memories of their stay as unpleasant. Furthermore, many caregivers lack sufficient understanding of the appropriate or indicated uses of drugs to allay patients' fears and pain. The use of suitable protocols for the proper titration of sedation of mechanically ventilated patients and monitoring of the level of sedation in ventilated patients may decrease the amount of time that patients are ventilated and may alleviate some of the emotional stresses of recall of painful procedures or uncomfortable mechanical ventilation. Future research into protocols for the care of the critically ill patient can enhance the overall well-being of these patients. PMID- 11762264 TI - Benzodiazepines in the intensive care unit. AB - The effects of BZ drugs result from interaction at the GABAA receptor within the CNS, producing anxiolysis, hypnosis, and amnesia in a dose-dependent fashion. These sedative effects are best titrated to reproducible clinical endpoints, using scoring systems such as the Ramsay scale. All BZs exhibit similar pharmacologic effects, but the important differences in pharmacokinetics and pharmacodynamics should be recognized to use these drugs safely and effectively within the ICU. Diazepam is the classic anxiolytic, amnestic, and sedative agent, but the presence of long-acting active metabolites that depend on the kidneys for elimination limits its use in many ICU patients. Lorazepam is the most potent BZ used in the ICU; it has stable pharmacokinetics and relatively low cost. This drug is best reserved for situations in which rapid onset is not essential and long-term sedation is anticipated. Midazolam has the shortest t1/2 of the commonly used BZs, generates few active metabolites, and is water soluble at physiologic pH. Thus, it is well suited for continuous infusion in the ICU, and the recent introduction of generic formulations of midazolam has decreased the drug-acquisition cost for many hospitals. Optimal sedation for ICU patients often requires BZ and concomitant therapy with drugs such as haloperidol, dexmedetomidine, opioids, and so forth, to reduce untoward side effects and, perhaps, overall drug costs. Flumazenil, a specific BZ antagonist, can be used for diagnostic or therapeutic reversal of BZ agonists when appropriate. Most experienced intensivists recommend an individualized approach to sedation and titration of anxiolysis to maximize efficacy, minimize side effects, and optimize cost effectiveness in the ICU. New CNS monitors of the EEG, such as the BIS or entropy EEG monitors, may refine titration algorithms further in the near future. PMID- 11762265 TI - Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. AB - Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed. PMID- 11762266 TI - New agents for sedation in the intensive care unit. AB - Several advances are likely to benefit the ICU patient requiring sedation, analgesia, and anxiolysis. The cooperative sedation induced by dexmedetomidine is a unique and valuable state that allows patients to be aroused easily and interferes little with ventilation. Remifentanil is the prototype of short-acting drugs, providing fast onset and offset; its relatively high cost may be balanced by limiting the risk for long-lasting respiratory depression. Lorazepam seems to be finding more proponents, especially in long-term ICU sedation where the costs of the newer agents may be prohibitive. PMID- 11762267 TI - Analgesic agents. Pharmacology and application in critical care. AB - Evaluation of analgesic agents is multifactorial. The authors know of no direct comparisons among the choices in analgesic agents that suggest one therapy over another in global outcomes such as mortality or morbidity. Therefore, until further outcome differentiation between agents is proved, understanding the primary difference of delivery routes, mechanisms of action, pharmacokinetics, and adverse effects serves as the best guide for selecting the appropriate agent for each patient. PMID- 11762268 TI - Neuromuscular-blocking drugs. Use and misuse in the intensive care unit. AB - The use of NMB agents for more than 24 to 48 hours in critically ill patients is associated with many potential complications. Neuromuscular-blocking drugs should be used only when their use is essential for optimal patient care. The indications for neuromuscular blockade must be defined clearly, and patients should be evaluated during treatment for the need for continued muscle relaxation. The smallest doses of NMB agents that will accomplish clinical goals should be used. This dosage can be determined through clinical evaluations and peripheral nerve monitoring. It is essential that all patients treated with NMB drugs receive appropriate sedation and analgesia. Myopathies, neuropathies, and alterations of the neuromuscular junction can occur in the ICU setting, and nondepolarizing muscle relaxants seem to be involved in the development of these disorders. Clinicians should be aware of risk factors that may predispose certain patients to neuromuscular complications, including sepsis and the use of high dose steroids. Neuromuscular-blocking agents should be avoided in these patients if possible. Although not proved, early recognition and treatment of iatrogenic neuromuscular complications may improve patient outcome. PMID- 11762269 TI - Regional analgesia in the intensive care unit. Principles and practice. AB - Nociception is a complicated process, and only in recent years have the neural pathways and mediators of pain transmission been unraveled. Several regional anesthetic interventions, most notably epidural drug delivery, can interrupt nociception and provide safe and effective pain control in critically ill patients while substantially reducing the need for systemic medications. This article discusses the possibilities for regional control of the neurobiology of nociception and describes the arsenal of regional anesthetic techniques available to the intensivist. Used wisely, regional techniques can provide excellent pain control and may have a significant role in improving overall patient outcome. Regional analgesia offers the best opportunity to provide substantial analgesia without significant central opioid effects. Well-conducted regional analgesia can reduce many of the unpleasant or potentially problematic side effects observed when traditional intravenous medications are used exclusively for pain control. PMID- 11762270 TI - Monitoring sedation, agitation, analgesia, and delirium in critically ill adult patients. AB - The recent development of valid and reliable assessment tools to monitor agitation, sedation, analgesia, and delirium in the ICU represents an essential first step in the provision of patient comfort and the development of preferred treatment strategies. To make the ICU a more humane healing environment, these assessment tools must be used as part of a comprehensive evaluation of interventional and preventive treatments, pharmacologic and nonpharmacologic. In the spirit of the JCAHO, it may be time to add the evaluation of sedation, agitation, and delirium to that of pain assessment, making all aspects of patient comfort the fifth vital sign for the critically ill. PMID- 11762271 TI - Using protocols to improve the outcomes of mechanically ventilated patients. Focus on weaning and sedation. AB - The use of nonphysician-directed protocols and guidelines for the management of sedation and weaning has been shown to reduce the duration of mechanical ventilation for patients with acute respiratory failure when compared with conventional physician-directed practices. Practitioners in ICUs frequently are needed to perform multiple tasks and to evaluate numerous elements of clinical information in the care of the critically ill. In this complex environment, protocols and guidelines are one strategy for ensuring that specific tasks are carried out in a timely manner. Simple-to-employ methods for facilitating changes and improvements in the care of hospitalized patients recently have been proposed. These methods emphasize the importance of developing a culture of cooperation within the ICU so protocols and guidelines can be implemented successfully. Such a culture should embrace changes in medical practices in the ICU if they are associated with improved clinical outcomes. The results of studies evaluating the use of protocols and guidelines have important implications for general critical care practices, because many ICUs do not have physicians who are constantly at the patient's bedside. The need for effective communication from the bedside caregiver (e.g., nurse, respiratory therapist, pharmacist, technician) to the physician, so that treatment orders can be changed appropriately, usually results in some delay in the implementation of treatment changes. Protocols are one method for potentially reducing those delays and ensuring that medical care is administered in a more standardized and efficient manner. PMID- 11762272 TI - Special situations: pediatric, pregnant, and geriatric patients. AB - Venous thromboembolic disease is not an uncommon problem associated with the geriatric patient. These patients are at significantly increased risk of DVT and PE compared with their younger counterparts. Their associated morbidity and mortality is also higher. Treatment of thrombotic disease in these patients necessitates close monitoring owing to their enhanced sensitivity to the effects of anticoagulants. PMID- 11762273 TI - Pharmacology of low molecular weight heparins. AB - Although intravenous heparin has been the treatment of choice for acute VTE disease, LMWHs are gaining wider recognition and support as not only a new option but also as the standard of care. Each LMWH is viewed as a unique drug by regulatory agencies because of their differing physical and pharmacokinetic attributes. LMWHs have high absorption, high bioavailability, and long half-lives enabling once- or twice-daily dosing with predictable dose-response relationships. These factors enable the LMWHs to be used without laboratory monitoring and at home for acute DVT management. Studies continue to show that LMWH preparations are as at least as effective as heparin in a variety of settings, including VTE disease prophylaxis, management of acute VTE disease, unstable angina, and NSTEMI. They are at least as safe as heparin relative to hemorrhagic complications. Heparin-induced thrombocytopenia is less of a problem with LMWHs. Use of LMWHs has resulted in cost benefits in the treatment of acute DVT, unstable angina, and NSTEMI as well as in prophylaxis against venous thromboembolism. Emergency physicians, because of their unique position at the forefront of acute care, will soon regularly use LMWHs. PMID- 11762274 TI - Epidemiology of venous thromboembolic disease. AB - From the information presented in this article, it can be concluded that clinical suspicion of VTE should be increased in patients with a history of VTE, recent surgery, spinal cord injury, trauma, or malignancy. A variety of medical illnesses also increase the risk of venous thrombosis, including congestive heart failure, myocardial infarction, stroke with paresis, nephrotic syndrome, cigarette smoking, and obesity. Hypercoagulable states, such as antithrombin III deficiency, protein C deficiency, protein S deficiency, or factor V Leiden mutation should be considered in those patients who develop VTE in the absence of known risk factors. Additionally, the presence of vena caval filters does not exclude the possibility of PE or recurrent DVT. With a careful assessment of risk, physicians can hope to increase the diagnostic yield of VTE and decrease the significant morbidity and mortality of caused by this disease. PMID- 11762275 TI - Assessment of pretest risk for venous thromboembolic disease. AB - The news, therefore, is somewhat pessimistic. Empiric estimate appears to be fairly good in stratifying risk groups for PE but suffers from a lack of standardization, as well as poor sensitivity and specificity. Multiple attempts to standardize pretest risk have used several different but usually overlapping variables, and none appears yet to be much better than simple clinical estimate- the very scale they were trying to replace. The clinician therefore must assess whether, on the basis of what has been published so far, there is any convincing reason to move from an empiric to a score-based prediction system. Apart from the clear advantage of standardization, the score-based systems are varied, not agreed on, and usually clumsy to use in a busy ED. Until one prediction system has been shown to be both easy to remember and use in clinical practice, and to be more accurate than an empiric score, emergency physicians should continue to use their own practice-based empiric system. DVT can be safely, quickly, and accurately diagnosed in the ED, and for most cases there is no need to use a prediction rule. Suspected PE continues to be a complex entity to evaluate and diagnose in the ED, and none of the objective prediction rules have yet been able to improve the difficult task of the ED evaluation of the patient with suspected PE. PMID- 11762276 TI - Physical examination findings in deep venous thrombosis. AB - DVT is a potentially serious disease and can serve as a marker for PE, an entity with even higher morbidity. Thus, it is critically important that emergency physicians consider this diagnosis in patients who present with suspicious symptoms. Recognition of alternative conditions, such as compartment syndrome, septic arthritis, and cellulitis, is also important for optimal care. Because physical examination is only 30% accurate for DVT, it serves to increase clinical suspicion in patients at risk but cannot be used to eliminate the possibility of thromboembolic disease. Because of this limitation, the diagnosis of DVT should be pursued using adjunctive testing in any patient with unexplained limb pain or swelling. Duplex sonography is currently the initial diagnostic study of choice for evaluation of DVT and, if test results are negative, it should be repeated serially if the clinical suspicion is high. PMID- 11762278 TI - The diagnosis of lower extremity deep venous thrombosis. AB - The diagnosis of lower extremity deep venous thrombosis (DVT) is critical to emergency physicians because of the risk of pulmonary embolism. This article reviews the diagnostic modalities available for patients with suspected lower extremity DVT. The use of compression ultrasonography and the recent advances in the D-dimer assays are emphasized. A clinical algorithm that utilizes a non invasive approach to this potentially life threatening disease is presented. PMID- 11762277 TI - Non-lower extremity deep vein thrombosis. AB - This article reviews the prevalence, etiology, pathophysiology, clinical manifestations, diagnoses, and treatment of non-lower extremity deep vein thrombosis (DVT). The discussion includes upper extremity DVT, mesenteric venous occlusion, jugular vein thrombosis, and central venous thrombosis. PMID- 11762279 TI - Treatment options for deep venous thrombosis. AB - Once the diagnosis of deep venous thrombosis (DVT) has been established the focus shifts to management of the disease. The goals of acute treatment of DVT are several: arrest growth of the thrombus, dissolve or remove the thrombus, and prevent embolizations of the thrombus. Although these goals have remained constant, the initial management of DVT has undergone a series of evolutions during the past decade, affecting both acute treatment and disposition decisions. As this article discusses, emergency medicine is at the cutting edge of these changes. PMID- 11762280 TI - Clinical manifestation of pulmonary embolism. AB - Results of prospective studies have shown that physicians' estimate of clinical likelihoods of PE have predictive value. The ability of clinicians to assess the factors that determine the probability of disease based on clinical manifestations such as history and signs and symptoms at presentation, and to make bedside estimates of that probability, has not been systematically studied. Data suggest that that this would be a fruitful area of future investigation. Susec et al noted that there has been a total of three studies (including their own) which have examined the clinical features such as risk factors, signs, and symptoms associated with PE in ambulatory outpatients. Hence, the data collected thus far might not be generalizable to the ED patient population. As with other illnesses, the ED patients usually present later and more atypically. The prevalence of PE could be lower among this population compared with hospitalized patients, causing a lower positive predictive value, derivable from the clinical features and risk factors at presentation. Finally, the ED patient population is usually healthier and younger than the hospitalized patients, and it is well recognized that PE can be clinically silent in young patients and that 28% have no associated risk factors. Based on their finding, the authors argue that clinical pathways to risk stratify patients in an ambulatory setting could be less useful than anticipated. The validity of these findings needs further investigation, however. PMID- 11762281 TI - Nonspecific tests for pulmonary embolism. AB - Many tests have been proposed as useful in the diagnostic evaluation of suspected PE, but nonspecific tests for PE can only add to the level of suspicion one has for the diagnosis. As Anderson indicates, "virtually all clinical and laboratory findings neither diagnose nor exclude the diagnosis of PE. They merely serve to heighten suspicion of the diagnosis and prompt the clinician to pursue additional diagnostic studies." D-dimer measurement is promising as a test to exclude PE in young healthy out-patients, and further study and improvements in technology, can clarify the usefulness of the different methods of performing this assay. For now, diagnostic algorithms for PE should continue to incorporate multiple tests and decision points, but the standard remains specialized imaging techniques. PMID- 11762282 TI - Ventilation/perfusion scintigraphy. AB - V/Q imaging is often very useful in evaluating patients in whom a PE is suspected. A normal scan result can be used to exclude embolism and a high likelihood ratio scan can be used to make the diagnosis of PE. Most patients with PE do not have high likelihood ratio scans; therefore, it is important to pursue this diagnosis in patients with intermediate likelihood ratio scans and in the appropriate clinical setting for patients with the low likelihood ratio scans. In patients with parenchymal chest x-ray abnormalities who are likely to fall into the intermediate category, it can be more appropriate to use CT angiography instead of V/Q scintigraphy. This strategy probably increases the fraction of scans with high diagnostic utility. PMID- 11762283 TI - Newer diagnostic modalities for pulmonary embolism. Pulmonary angiography using CT and MR imaging compared with conventional angiography. AB - CTPA is a highly sensitive and excellent primary method for evaluating patients with symptoms of PE. Ongoing studies will demonstrate the good clinical outcome of patients with negative CTPA results. The ability to visualize the lung parenchyma in addition to the pulmonary vasculature, and the smaller number of nondiagnostic scans, make CT more cost effective than V/Q scans, and CT therefore should be used as a first-line evaluation. MR imaging is a continually developing modality with more imaging options that could make it an invaluable or adjunctive test in the near future. PMID- 11762284 TI - Emergency department management of pulmonary embolism. AB - There are several points that bear repetition. First, consider the diagnosis of PE in all patients presenting with chest pain, dyspnea, syncope, oxygen desaturation, or unexplained hypotension. Evaluate these patients in a rational manner. At any individual hospital, develop algorithms with consultants so that when one is faced with a patient with a PE, the flow of both diagnostics and therapeutics flows smoothly and rapidly. Consider the concept of risk stratification, and remember that not all patients with PE are created equal. In particular, be on the same page with all consultants regarding the use of right heart echocardiography, both for its potential diagnostic capabilities and for its ability to identify patients who could be at greater risk for bad outcomes. PMID- 11762285 TI - The electronic health record files 2 computers. E-health, patient empowerment and the cultural change. PMID- 11762287 TI - Proceedings of the 1st World Water Congress: Part 4, wastewater treatment. Paris, France, 3-7 July 2000. PMID- 11762288 TI - Wolfgang Beermann. 1921-2000. (133-135). PMID- 11762289 TI - [The usefulness of the application of nonlinear dynamics in the analysis of electrocardiograms in Chagas' disease patients]. AB - INTRODUCTION AND OBJECTIVES: The application of nonlinear techniques allows the definition of early risk markers in patients with Chagas infection and without any evidence of cardiac involvement evaluated by standard diagnostic test. Nonlinear modeling techniques have proved to be effective in cardiac rhythm analysis, thereby justifying its use in Chagas' disease. PATIENTS AND METHOD: The routine noninvasive test and heart rate variability analysis were performed in Chagas' disease patients and in a group of healthy subjects. In a second phase we used nonlinear analysis in the evaluation of patients with Chagas infection and no evidence of heart disease, Chagasic patients with minimal electrocardiographic abnormalities and healthy controls. RESULTS: Twenty-four-hour electrocardiographic ambulatory monitoring and heart rate variability allowed us to establish differences between the healthy subjects and patients with Chagas infection without evidence of cardiac disease (p c 0.05 and p <0.005). In sharp contrast nonlinear analysis characterized 4 subgroups in Chagasic patients without cardiac involvement (sensitivity and specificity of 1 00%). CONCLUSIONS: Our findings suggest that nonlinear modeling techniques have a high sensitivity and specificity in the early detection of cardiac involvement and very early autonomic disturbance. We recommend that these techniques be applied to patients with high risk of cardiac disease other than Chagasic myocarditis. Our findings should be corroborated with studies in larger populations. We are currently developing a prospective study to this end. PMID- 11762290 TI - [Agonist-antagonist mechanics of the descendent and ascendent segments of the ventricular myocardial band]. AB - In this article the macroscopic structure of the ventricular myocardium is described, which is configurated as a band along which four segments can be distinguished. Such band traces a helicoids with two spiral turns in the space, in its trajectory from the pulmonary artery root to the aortic root, delimits both ventricular cavities. Our interest in achieving the knowledge of the coherent relationship between that anatomical fact and cardiac mechanics, which necessarily exist between the form and the function of any organ, has led us to perform some experimental approaches which show that the volume decrease of the ventricular cavities takes place, simultaneously with the descent of the base, thanks to the agonist contraction of the descending segment of the band, previously stretched out in a rectilinear way. Meanwhile, the volume increase takes place, simultaneously with the ascent of the base, as a consequence of the antagonist contraction of the ascendent segment of the band, previously extended in a curvilinear way. PMID- 11762291 TI - [Chest pain units: state of the art of the management of patients with chest pain in the emergency department]. AB - Chest pain is one of the most common reasons for patients coming to emergency departments. Most of these individuals end up being hospitalized due to uncertainty of the cause of their complaint. This aggressive and defensive attitude is taken by emergency physicians because some 10 to 30% of these patients actually have acute coronary syndrome. As the admission electrocardiogram and serum CK-MB level have a sensitivity of about 50% for the diagnosis of acute myocardial infarction, serial evaluation is mandatory for non low risk patients. Inspite of this knowledge, an average of 2-3% of patients with acute myocardial infarction are erroneously released from emergency departments, what is responsible for expensive malpractice suits in the United States. Chest Pain Units were introduced in emergency practice two decades ago to improve medical care quality, reduce inappropriate hospital discharges, reduce unnecessary hospital admissions and reduce medical costs, thus making patient's assessment cost-effective. This is achieved mostly with the use of systematic diagnostic protocols by qualified and trained personnel in the emergency department setting and not in the coronary care unit. PMID- 11762292 TI - [Congenital stenosis of pulmonary veins: long-term efficacy after intraluminal dilatation]. AB - We present a 7-month-old infant diagnosed with congenital pulmonary vein stenosis. Cardiac catheterization showed two sequential stenoses of the superior left pulmonary vein and balloon angioplasty was performed. The gradient decreased from 20 to 4 mmHg and pulmonary artery pressure from 75/35 mmHg to 44/28 mmHg. The diameter of the stenoses increased from 2 and 3.5 mm, respectively, to 6 mm. Fourteen years after the procedure the patient is asymptomatic with normal cardiac examination. PMID- 11762293 TI - [Fibrinolytic treatment with tissue plasminogen activator in a thrombosed modified Blalock-Taussig shunt]. AB - Thrombolytic therapy of a systemic pulmonary fistula is a rare method of treatment in newborns with thrombosed systemic-pulmonary shunt. We report the case of a newborn girl with a complex congenital heart defect. On the ninth day of life a modified right Blalock-Taussig shunt was performed. The ductus arteriosus was not ligated. Six days later the baby developed severe hypoxemia. The results of echocardiography and cardiac catheterization showed a total thrombosis of the fistula and complete absence of flow throughout the shunt. After insertion of an arterial catheter into the proximal end of the shunt we started fibrinolytic treatment with recombinant tissue plasminogen activator (r TPA) in continuous infusion. After 14 hours of treatment we confirmed by angiography complete clot dissolution. The baby left the hospital in good condition when she was 23 days old. In the follow-up (4th month of life) the shunt is still permeable. Thrombolytic therapy with r-TPA locally applied in case of acute thrombosis of a systemic-pulmonary shunt appears to be a good therapeutic option avoiding the risks of a new surgical procedure. PMID- 11762294 TI - [Prevalence of white-coat hypertension in a geriatric population with a diagnosis of isolated systolic hypertension]. AB - The aim of this study was to determine the frequency of white-coat hypertension in geriatric subjects with isolated systolic hypertension. We included 80 elderly patients with a previous diagnosis of isolated systolic hypertension, who performed self-measurement of blood pressure at home during 3 days after a 2-week washout period. Patients with home blood pressure values <135/85 performed a second self-measurement of blood pressure one month later. We found that 20 patients (25%, 18 women, RR=2.6), showed normal blood pressure values at home in both studies of self-measurement. Knowledge of the prevalence of white-coat hypertension is important for adequate diagnosis, and to avoid the use of unnecessary antihypertensive drugs. PMID- 11762295 TI - [Cholesterol crystals pericarditis]. AB - Cholesterol pericarditis is an uncommon, specific form of pericardial disease that is characterized by the presence of cholesterol crystals in pericardial fluid. The etiology may be either idiopathic or in association with systemic disorders such as tuberculosis, rheumatoid arthritis, myxedema or hypercholesterolemia. We report a case of cholesterol pericarditis in a 51-year old male who was diagnosed with chronic renal failure due to polycystic kidney disease. To our knowledge no similar cases have been reported to date in the literature. PMID- 11762296 TI - [National Days of Laboratory Medicine of Russia-2001. Scientific and Practical Workshop "Philosophy and Methods of Laboratory Support of Outpatient Care and Current Problems of Laboratory Medicine"]. PMID- 11762297 TI - [National Days of Laboratory Medicine of Russia-2001. Scientific and Practical Workshop "Philosophy and Methods of Laboratory Support of Outpatient Care and Current Problems of Laboratory Medicine"]. PMID- 11762298 TI - Infectious and tropical diseases in the Middle East. Proceedings of an international congress. Oman, 2000. PMID- 11762299 TI - 77th Congress of the European Orthodontic Society, Ghent, Belgium. PMID- 11762300 TI - Immunologic tolerance: the good, the bad, and the ugly. PMID- 11762301 TI - Information for patients. Inhaled corticosteroids in asthma. PMID- 11762303 TI - [Proceedings of the 35th Annual Meeting of the German Society for Biomedical Engineering. 19-21 September 2001]. PMID- 11762302 TI - Free radicals and antioxidants in the development and functions of the central nervous system: from fetus to aging. April 18-20, 2001. Saint Petersburg, Russia. Abstracts. PMID- 11762305 TI - Current readings in nuclear medicine. PMID- 11762304 TI - [What caused the stroke?]. PMID- 11762306 TI - Correction: exposure measurement error in time-series air pollution studies. PMID- 11762307 TI - Confirmation of uterotrophic activity for 4-MBC in the immature rat. PMID- 11762308 TI - EU sewers still not up to standard. PMID- 11762309 TI - New risk for newborns. PMID- 11762310 TI - Molding better plastics with clay. PMID- 11762311 TI - The Tokyo attacks in retrospect: sarin leads to memory loss. PMID- 11762312 TI - Bad news for boys: linking hypospadias and endocrine disruptors. PMID- 11762313 TI - How risky is rover? Petting transfers pesticides. PMID- 11762314 TI - President Bush announces limited federal support for human embryonic stem cell research: beyond the great divide. PMID- 11762315 TI - Neuroimaging to develop in African centers of excellence. PMID- 11762316 TI - Who to publish landmark report based on mental health status in Africa. PMID- 11762317 TI - [Membrane properties and innervation of the aganglionic segment of smooth muscle in Hirschsprung's disease]. PMID- 11762318 TI - Lack of association of neprilysin polymorphism with Alzheimer's disease and Alzheimer's disease-type neuropathological changes. PMID- 11762319 TI - Human T lymphotropic virus type I (HTLV-1) associated myelopathy acquired through a liver transplant. PMID- 11762320 TI - Relation between the high production related allele of the interferon-gamma (IFN gamma) gene and age at onset of idiopathic Parkinson's disease in Japan. PMID- 11762321 TI - Autonomic dysreflexia due to neurogenic bladder dysfunction; an unusual presentation of spinal cord sarcoidosis. PMID- 11762322 TI - The late whiplash syndrome: a biopsychosocial approach. PMID- 11762323 TI - Rene Theophile-Hyacinthe Laennec: Laennec's cirrhosis. PMID- 11762324 TI - Treatment of symptomatic diffuse esophageal spasm by endoscopic injection of botulinum toxin: a prospective study with long term follow-up. PMID- 11762325 TI - A risk score to predict need for treatment for upper GI hemorrhage. PMID- 11762326 TI - Intestinal metaplasia is the probable common precursor of adenocarcinoma in Barrett's esophagus and adenocarcinoma of the gastrica cardia. PMID- 11762327 TI - Put patient safety process changes to the test. PMID- 11762328 TI - Abstracts of the 24th Annual San Antonio Breast Cancer Symposium. San Antonio, Texas, USA. December 10-13, 2001. PMID- 11762329 TI - High temperature in-situ XRD of plasma sprayed HA coatings. AB - The control of phase transformations in plasma sprayed hydroxyapatite (HA) coatings are critical to the clinical performance of the material. This paper reports the use of high temperature X-ray diffraction (HT-XRD) to study, in-situ, the phase transformations occurring in plasma sprayed HA coatings. The coatings were prepared using different spray power levels (net plasma power of 12 and 15 kW) and different starting powder size ranges (20-45; 45-75 microm). The temperature range employed was room temperature (approximately 26 degrees C) to 900 degrees C in normal atmosphere and pressure. High temperature differential scanning calorimetry (DSC) was also employed to investigate and determine the precise onset temperature of phase transformations during the recrystallization process. Results showed that actual onset of thermal degradation in the coating into other metastable phases like TTCP, beta-TCP and CaO occurred at 638 degrees C. The aforementioned phase transitions were independent of the selected spraying parameters. The degree of melting and thermal dissociation of HA actually determines the amount of calcium phosphate phases that are formed. A high power level of 15 kW produced a greater degree of melting, resulting in more CaO, TTCP and beta-TCP being formed as a result. PMID- 11762330 TI - Blood-compatible biomaterials by surface coating with a novel antithrombin heparin covalent complex. AB - Covalent antithrombin-heparin complex (ATH) was covalently grafted to a polycarbonate urethane (Corethane) endoluminal graft (a kind gift of Corvita Corporation) after being activated using 0.3% m/m NaOCl in 0.15 M phosphate pH 6.0. ATH graft density (1.98 x 10(-7) mol/m2) was 6 times the maximum amount of unfractionated heparin (UFH) that could be bound to polycarbonate urethane surfaces. Surface-bound ATH could be stored in sterile 0.15 M NaCl at 4 degrees C for at least 2 months with good antithrombotic activity before being implanted into rabbits. Analysis of ATH-coated tubing showed that it contained significant direct thrombin inhibitory activity. In vivo testing in a rabbit model was compared to non-activated non-coated surfaces, activated-non-coated surfaces, hirudin-coated surfaces and antithrombin (AT)-coated surfaces. The weight of the clot generated in the ATH-coated graft tubing was significantly less than the weight of the clot generated within the hirudin-coated graft (p = 0.03 with a 1 tailed Student's t test). The anticoagulant nature of ATH grafts in vivo was shown to be due to bound ATH because boththe AT-coated surfaces and non-coated but activated surfaces showed similar thromboresistant efficacy to that of untreated material (ANOVA; p < 0.05). Apart from the direct antithrombin activity that contributed to much of the prolonged patency in vivo, surface-bound ATH likely catalyzed AT inhibition of thrombin, as evidenced by a significant number of 125I-AT binding sites (> or = 1.5 x 10(-8) mol/m2). Thus, ATH appears to be a good candidate for coating cardiovascular devices, such as endoluminal grafts, with high levels of substitution and significant long-term blood-compatibility. PMID- 11762331 TI - Particle size effect on structure and properties of dispersed Pd-containing dental amalgam. AB - Focus of the study is to evaluate the effect of dispersant particle size on the structure and various properties of spherical matrix, irregular dispersant admixed type Pd amalgams. The results indicate that amalgams prepared from smaller dispersant particles have a shorter setting time (faster amalgamation reaction), smaller setting expansion, higher eta' content and lower early stage gamma2 content. Smaller dispersant particles also lead to a slightly higher compressive strength, lower creep value, more cathodic corrosion potential and less early stage mercury vapor release. The particle size effect on corrosion current density and chemical composition of gamma1 phase in aged amalgam is less significant. PMID- 11762332 TI - British Thoracic Society winter meeting 2001. London, United Kingdom. 5-7 December 2001. Abstracts. PMID- 11762333 TI - Surgical strategy in the treatment of gastrointestinal neuroendocrine tumours. AB - The aim of this study was to analyze the indications and type of surgery to be performed in patients suffering from the more common gastrointestinal neuroendocrine tumours. The different patterns of tumour spread are considered (local, locoregional and metastatic disease) along with the indications according to three main objectives, namely, identification of the disease, cure and care. The surgical procedures of choice in relation to the different tumour subtypes are also analyzed, and the main controversies relating to cytoreductive surgery are discussed. PMID- 11762334 TI - The clinical management of neuroendocrine tumors with long-acting repeatable (LAR) octreotide: comparison with standard subcutaneous octreotide therapy. AB - Neuroendocrine tumors are rare, occurring in less than 1% of the population. They are divided clinically into functionally active or non-active tumors. Functionally active tumors produce a variety of substances (mainly peptides or serotonin) that are responsible for symptoms and sometimes can lead to the death of the patient independently from tumor proliferation. The most important compounds that can control symptoms in these patients are somatostatin analogs. Native somatostatin is not suitable for long-term clinical application due to its short half-life. Therefore, synthetic drugs were developed with improved pharmacokinetic characteristics. The best-characterized analog, octreotide, has been successfully applied to patients with functioning tumors. Octreotide can ameliorate symptoms in 30%-70% of the patients, mainly through a direct inhibitory effect on hormone production from the tumors. There is little or no effect on tumor growth during octreotide therapy; clinical responses were recorded in only 10%-30% of the patients. Recently, significant improvement in the management of the disease has been demonstrated with long-acting repeatable (LAR) octreotide. This new formulation requires only one monthly intramuscolar injection, and shows better acceptability and patient compliance to therapy. Data available to date show superimposable results of both standard octreotide and LAR octreotide in controlling symptoms, lowering hormone and tumor marker levels, and in reducing tumor growth. The availability of long-acting molecules have permitted the exploration of high-dose therapy in increasing tumor shrinkage and prolonging survival. Although there is a clear dose-response trend, the published data are not conclusive and further investigations are needed. The possible lack of cross-resistance between LAR octreotide and a different analog, Lanreotide, is a very stimulating finding and this might lead to the development of new therapeutical strategies in the management of neuroendocrine tumors. PMID- 11762335 TI - Chemotherapy and biotherapy in the treatment of neuroendocrine tumours. AB - The medical treatment of neuroendocrine GEP tumours must be based on the growth properties of the tumour. Medical treatment includes chemotherapy, somatostatin analogues and alpha interferons. Chemotherapy has been particularly active in patients with high proliferating neuroendocrine tumours such as endocrine pancreatic tumours and lung carcinoids. Streptozotocin-based combinations including 5-flourouracil and doxorubicin have generated partial remissions in 40% 60% of the patients giving a median survival of about two years in patients with advanced disease. Cisplatinum plus etoposide have demonstrated significant antitumour effects in anaplastic endocrine pancreatic tumours and lung carcinoids. However, in low proliferating tumours such as classical midgut carcinoids the response rates with the same combinations of cytotoxic agents have only generated short lasting responses in less than 10% of patients. In these patients, biological treatment has been of benefit. Alpha interferon at doses of 3-9 million units three to seven times per week subcutaneously, has given biochemical response rates of 50% and significant tumour reduction in about 15% of patients with long duration, up to three years. Somatostatin analogues have been widely used in the treatment of neuroendocrine gut and pancreatic tumours. The currently available somatostatin analogues particularly bind somatostatin receptor 2 and 5 and with low affinity also receptor subtype 3. Octreotide is registered in most countries for the treatment of patients with carcinoid syndrome and also VIP and glucagon producing tumours. Regular octreotide at standard doses of 100-300 microg/day gives symptomatic responses in a medium of 60% of patients and biochemical responses in up to 70% of patients. Significant tumour responses are rare, less than 5%. Long-acting formulations of somatostatin analogues have been of significant benefit for the patients with similar response rates as for regular formulations. The quality of life has been significantly improved by using the long-acting formulations. PMID- 11762336 TI - Clinical significance of neuroendocrine carcinoma of the breast. AB - BACKGROUND: Neuroendocrine (NE) carcinomas of the breast are defined by the diffuse expression of NE markers. This definition includes lesions with 'pure' NE phenotype as well as 'variants' which may co-express mucinous and/or apocrine phenotype. In the present work, the clinical significance of pure' NE differentiation in breast carcinoma and of its 'variants' will be analyzed. MATERIALS AND METHODS: Forty-three NE breast carcinomas immunocytochemically positive for chromogranins and/or synaptophysin in > or = 50% of cells were graded following the Elston and Ellis grading system for breast carcinomas. The production of mucin and the expressionof the apocrine marker Gross Cystic Disease Fluid Protein-15 (GCDFP-15) were correlated with the grade and the hormonal receptor status. The clinical outcome of patients was also analyzed. RESULTS: The histological grade highly influenced the clinical evolution of NE breast carcinomas. We confirmed that mucinous differentiation is an important indicator of low biological aggressiveness. Estrogen and progesterone receptor expression was also correlated with a better prognosis. Presence of androgen was correlated with the expression of GCDFP-15 in NE tumors. CONCLUSIONS: The histological grade overcomes the immunophenotype in determining the prognosis of NE differentiated carcinomas of the breast. Co-expression of exocrine products in such tumors is related to hormone dependency. PMID- 11762337 TI - Clinical significance of neuroendocrine phenotype in non-small-cell lung cancer. AB - Non-small-cell lung carcinoma (NSCLC) describes a histologically heterogeneous group of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but clinical outcomes in individual patients remain unpredictable. A significant minority of NSCLCs (10%-30%) show neuroendocrine (NE) differentiation, and a number of studies have attempted to evaluate the therapeutic and prognostic significance of the expression of NE markers on the basis of the theoretical assumption that NE differentiated tumours may be associated with an adverse prognosis and greater chemosensitivity. However, the results of these studies are conflicting: some have found that NE differentiation has a negative impact on survival, but others have failed to demonstrate any correlation with prognosis. Similar discrepancies have also been observed in terms of chemosensitivity. Nevertheless, these data are difficult to interpret because there is no gold standard defining NE differentiation, as is shown by the fact that the proportion of NE-differentiated NSCLCs varies according to the technique and marker used, although chromogranin A and synaptophysin show the best correlation with ultrastructural evidence of NE differentiation. In conclusion, there is no doubt that caution is required when interpreting the results of a number of studies questioning the clinical impact of the NE features of NSCLCs. PMID- 11762338 TI - Neuroendocrine aspects of immunolymphoproliferative diseases. AB - Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation and mitogenesis, and immune cells may produce neuropeptides as well. Neuropetide Y is synthesized in B-cell leukaemia lymphoblasts, while substance P immunoreactivity has been detected in neoplastic haematological samples of different types of leukaemias. The presence of receptors for neuropeptides on different animal and human lymphoid cell lines, as well as in several types of animal and human lymphoproliferative diseases has been demonstrated. Species variability in receptor distribution has been shown as well. Receptor expression in immune cells may be regulated by changes in microenvironmental conditions, it may also be related to the activation and/ or proliferation state of cells. Vasoactive intestinal peptides receptors have been detected in myeloma cells, while somatostatin receptors have been first detected in vitro on resting lymphocytes and cells of the monocyte/macrophage lineage, and later on human activated lymphocytes and on lymphoblastic leukaemia cells. Somatostatin receptors have been found in biopsies from patients with malignant lymphomas. Tumor localization in non-Hodgkin lymphomas and Hodgkin's disease can be visualized by in vivo somatostatin receptor scintigraphy, contributing to establish the diagnosis and the stage of the disease. Recently. somatostatin receptors have been in vivo and in vitro detected in human thymic tumors. Although treatment of lymphoproliferative diseases with somatostatin analogs is a little explored field, partial remission was found in patients with low-grade non Hodgkin lymphoma and cutaneous T-cell lymphoma, and a successful treatment with octreotide has been reported in patients with thymoma. Specific somatostatin receptors present in progenitors of immune cells are not expressed in the mature phenotype, while they can be detected in transformed cell lines. The possibility that this phenomenon is caused by oncogene expression cannot be ruled out. Moreover, preliminary data showed a developmental expression of somatostatin receptors in lymphoid cells, suggesting a potential role for neuropeptide receptors as differentiation markers. Although controlled studies are warranted to investigate the efficacy of the currently available analogs, somatostatinergic compounds may be of interest in the treatment of lymphoproliferative malignancies. A promising approach in refractory patients with somatostatin receptor positive malignant lymphomas may be radionuclide-targeted and cytotoxic analog therapy. These concepts increase the possibility of a wider antitumor treatment with ligands for neuroepeptide receptors than in established 'classic' neuroendocrine tumors. PMID- 11762339 TI - Oncogenes, growth factors, receptor expression and proliferation markers in digestive neuroendocrine tumours. A critical reappraisal. AB - BACKGROUND: The main characteristic of the digestive neuroendocrine tumours (dNETs) is the low proliferating activity, even in the presence of malignant, metastatic behavior. PATIENTS AND METHODS: Considering that dNETs are rare diseases, relatively numerous studies, often including a conspicuous number of patients, have recently investigated the molecular mechanisms of neuroendocrine tumour genesis. RESULTS: In contrast to non-endocrine tumours of the digestive system such as carcinoma of the pancreas, colon and stomach, dNETs do not show alterations in oncogenes (ras, Myc, fos jun, Src) or in common tumor suppressor genes [p53, retinoblastoma suspectibility gene (Rb)]. MEN-1 gene alterations will likely be important in a proportion of sporadic dNETs. The role of various growth factors, novel oncogenes and tumour suppressor genes have also been investigated. However, results from these studies are non-conclusive and to date the molecular pathogenesis of these tumours has not been clarified. Studies on somatostatin receptor expression and synthetic analogues, as growth inhibitors in dNETs, although promising, have not reproduced in vivo all the antiproliferative effects showed in in vitro models. CONCLUSION: Although various functional genes and molecular mechanisms have been investigated in dNETs, to date the molecular pathogenesis of these tumours remains to be elucidated. PMID- 11762340 TI - Neuroendocrine tumors in the brain. AB - Somatostatin and other neuropeptides are expressed in tumors originating from neuronal precursors and paraganglia, namely medulloblastoma, central Primitive Neuro-Ectodermal Tumors (cPNETs), neurocytoma, gangliocytoma. olfactory neuroblastoma, paraganglioma. In medulloblastoma, the most common malignant tumor in childhood, there is an extensive expression of somatostatin in addition to somatostatin receptors (SSTR) type 2. Although density of SSTR-2 and intensity of expression of somatostatin genes have no prognostic significance in medulloblastoma. their presence may bring along important information on oncogenesis and relate medulloblastoma to cPNETs. Radio-labeled octreotide scintigraphy may be useful in the follow-up of these patients. allowing differentiation between scar and tumoral tissue. Moreover, on the basis of octreotide-induced inhibition of cell proliferation in medulloblastoma, a trial with octreotide in patients with recurrent or high-risk tumor is warranted. Meningiomas and low-grade astrocytic gliomas, even if not displaying a clear neuroendocrine phenotype, have high levels of SSTR-2. In meningiomas, SSTRs scintigraphy is not part of the routine pre-operative assessment; moreover, a therapeutic trial with somatostatin-analogues in patients with recurrent or inoperable meningiomas should be carried-out with great caution, because somatostatin and octreotide slightly increase cell proliferation in cultured meningiomatous cells. Low-grade gliomas (WHO grade 2), and a smaller fraction of anaplastic astrocytomas, express SSTR-2, while glioblastomas usually do not. Unfortunately, radiolabeled-octreotide scintigraphy is not useful in the differential diagnosis of gliomas, because the results are altered by the disruption of the blood brain barrier (BBB); in addition, radionuclide-labeled somatostatin analogues are not useful in the therapy of low-grade gliomas, because the intact BBB prevents them from reaching the target SSTR-2. Recently, a pilot study in gliomas, has proposed the use of a radio-labeled somatostostatin analogue with a loco-regional approach in order to overcome the intact BBB. PMID- 11762341 TI - Neuroendocrine differentiation in prostatic carcinoma: an update on recent developments. AB - The most recent developments relating to neuroendocrine differentiation in prostate cancer are reviewed. In vivo and in vitro experimental models of neuroendocrine differentiation in prostate cancer are emphasized with a discussion of their fidelity to the actual human in vivo situation. The contribution of these models to our understanding of the process of neuroendocrine differentiation and the mechanisms by which neuroendocrine differentiation can affect prognosis is discussed. Finally, an hypothosis is proprosed integrating neuroendocrine differentiation into more traditional models of the evolution, differentiation pathways and progression of prostate cancer, particularly in the androgen independent state. PMID- 11762342 TI - Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status. AB - BACKGROUND: The frequent occurrence of neuroendocrine (NE) differentiation in common prostatic malignancies has attracted increasing attention in contemporary prostate cancer research. METHODS: The present review focuses on growth properties and the androgen receptor (AR) status of NE phenotypes, and discusses their morphogenetic origin in benign and malignant prostate tissue. RESULTS: Recent data have documented a phenotype link between NE cells and other cell lineages encountered in benign and malignant prostate tissue. NE tumor cells (as defined by the most commonly used endocrine marker chromogranin A) do not proliferate or show apoptotic activity. This particular phenotype also lacks the nuclear AR in both benign and malignant conditions. CONCLUSIONS: Prostatic NE cells most likely derive from local stem cells and represent terminally differentiated and androgen-insensitive cell populations in benign prostate tissue. The frequent occurrence of NE differentiation in prostatic adenocarcinoma obviously reflects the differentiation repertoire of its stem cells. Neoplastic NE cells devoid of nuclear AR constitute an androgen-insensitive cell population in prostate cancer. The absence of proliferative and apoptotic activity may endow NE tumor cells with relative resistance towards cytotoxic drugs and radiation therapy. PMID- 11762343 TI - Neuroendocrine pathogenesis in adenocarcinoma of the prostate. AB - BACKGROUND: In the prostate, the importance of sex hormones for its normal development and function is well known. However, it has been proposed that various neuroendocrine (NE) hormones and growth factors may be involved in the pathogenesis of prostatic carcinoma (CaP). Neuroendocrine differentiation appears to be associated with tumour progression and the androgen-independent state, for which there is currently no successful therapy. Therefore, we need to improve our understanding of NE cells, their regulatory products and influence on the prostate gland. Finally, new therapeutic protocols need to be developed. METHODS: Information is presented on prostatic NE cells and neuroendocrine differentiation (NED) in prostatic carcinoma. Neuroendocrine secretory products and interactions with epithelial prostate cells are investigated in order to understand their significance for the pathogenesis of the prostate gland, prognosis and therapy. RESULTS: Recent research suggests that NE-secreted products. such as serotonin, somatostatin and bombesin, may influence growth, invasiveness, metastatic processes and angiogenesis in CaP. During recent years. new experimental models for NED have been developed to provide evidence that NE products may promote proliferation and confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to NE cells. Cancerous epithelial cells may become more responsive to NE factors by upregulation of receptors for neuropeptides, or may induce NE cells to upregulate the secretion and synthesis of NE factors. In the androgen independent state, neuropeptides and their intracellular signals may activate the androgen receptor. Furthermore, androgen ablation may lead to downregulation of neural endopeptidase 24.11 (a zinc-dependent metalloproteinase) and PSA, which would lead to increased levels of NE products becoming available. These studies confirm that NE cells and NED may have a significant impact on prostate cancer, especially in the androgen independent state. CONCLUSIONS: Recent developments in molecular biology and pathophysiology of prostate cancer have increased our understanding of the NE regulatory mechanisms. Hopefully, this will lead to the development of entirely new therapeutic modalities. For example, somatostatin agonists may suppress angiogenesis and proliferation, and simultaneously promote apoptosis in prostate cancer cells. Somatostatin may thus have an important role in tumour biology, and in the future there may be a potential role for somatostatin analogues in the treatment of prostate cancer, but also for serotonin and bombesin receptor antagonists. However, a review of the accumulated knowledge in this field suggests that we still need to improve our understanding of NE cells and their regulatory products and influence on the prostate gland. and that clinical trials are needed, to test drugs based on neuroendocrine hormones and their agonists/antagonists. PMID- 11762344 TI - Potential clinical value of circulating chromogranin A in patients with prostate carcinoma. AB - BACKGROUND: Neuroendocrine (NE) differentiation of prostate adenocarcinoma has received increasing attention in recent years as a result of possible implications for prognosis and therapy. The presence of NE tumor subpopulation can be gauged non invasively by measuring circulating levels of secretory products, primarily chromogranin A (CgA). METHODS: This article provides a review on published papers evaluating circulating CgA in prostate cancer patients. RESULTS: Circulating CgA levels were found to be higher in prostate cancer patients than in patients with benign or pre-malignant prostatic diseases. In patients with malignancy, they correlated either to the stage of disease or to the condition of hormone refractoriness. CgA levels did not correlate with serum prostate specific antigen (PSA) and were supranormal in the majority of advanced patients with PSA within normality. In hormone refractory cases, elevated CgA was a significant predictor of poor prognosis, independently from serum PSA. CgA values were not substantially affected by either endocrine therapy or chemotherapy. They were found to increase during androgen deprivation in some cases and this trend preceded that of PSA. The administration of a somatostatin analog in hormone refractory cases was able to reduce plasma CgA values consistently. CONCLUSIONS: Present data suggest a potential role of circulating CgA in the management of prostate cancer patients. CgA determination may be useful diagnostically and prognostically and could offer complementary information with respect to PSA. Serial evaluation of circulating CgA could provide information on changes in the NE phenotype expression as a consequence of tumor progression and/or treatment administration. PMID- 11762345 TI - Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma. AB - PURPOSE: The biological behaviour of prostate cancer is highly variable and prediction by the commonly employed prognostic parameters is not sufficient. The concept of neuroendocrine (NE) differentiation in prostate adenocarcinoma has recently received increasing attention due to possible implications for prognosis and therapy. MATERIALS AND METHODS: Core needle biopsies from 142 newly diagnosed patients were immunohistochemically examined for the coexistence of NE differentiation using an antibody against chromogranin A (CgA). Circulating CgA was available in 106 of these patients. RESULTS: NE differentiation was found in 64 (45.1%) tumors. Among them 29 (20.4%) had CgA positive cells scattered or focally distributed in less than 5% per mm3 of tumor tissues, 26 (18.3%) between 5% and 10% and 9 (6.4%) more than 10%, respectively. There was a significant correlation between the extent of NE features and either Gleason score (P < 0.01) or stage of disease. Circulating CgA but not PSA correlated with immunohistochemical CgA (P < 0.03) particularly in metastatic cases. CONCLUSIONS: These data support the concept that NE differentiation in human prostate cancer has a negative prognostic significance. Circulating CgA levels reflect immunohistochemical findings. PMID- 11762346 TI - Nerve-driven immunity: neuropeptides regulate cytokine secretion of T cells and intestinal epithelial cells in a direct, powerful and contextual manner. AB - Throughout the body, immune cells of various types, both classical (such as T cells) and less recognized (such as intestinal epithelial cells) are exposed to a variety of neurotransmitters secreted from local nerve fibers. Moreover, immune cells express specific neurotransmitter receptors. Based on the above we asked whether neurotransmitters. by direct interaction with their receptors, can either evoke or block immune functions in general, and cytokine secretion in particular. We found that several neuropeptides (SOM, Sub P, CGRP and NPY), in nM concentration and in the absence of any additional stimulatory molecules, induced a significant secretion of cytokines from Th0, Th1 and Th2 antigen specific T cells. Moreover, some neuropeptides surprisingly drove committed Thl and Th2 populations to a 'forbidden' cytokine secretion: secretion of Th2 cytokines from Th1 cells, and vice versa. We further found that SOM by itself markedly affected the secretion of proinflammatory cytokines from intestinal epithelial cells, which play a major role in the gut immunity in the mucosal defense against invading microorganisms. Thus, somatostatin, through its specific receptor, inhibits (> 90%) of the spontaneous, TNF-alpha or bacteria (Salmonella)-induced secretion of IL-8 and IL-1beta from two intestinal epithelial cell lines. Taken together, these observations suggest that neuropeptides can by themselves induce both typical and atypical cytokine secretion from T-cells and intestinal epithelial cells. Since a myriad of immune reactivities are mediated by, and dependent on, specific cytokines secreted from immune cells, the neuropeptide induced effects may have important implications for numerous physiological and pathological conditions, including autoimmune diseases, chronic inflammation and neoplasias. PMID- 11762347 TI - Expression of neuropeptide Y receptors in human prostate cancer cells. AB - BACKGROUND: Neuroendocrine molecules are now believed to play a significant role in the progression of human prostate cancer (CaP), especially in the androgen independent stage. MATERIALS AND METHODS: In the present study, we evaluated the presence and the function of the receptors for neuropeptide Y (NPY) in human CaP cell lines (the androgen-dependent LNCaP, and the androgen-independent DU 145 and PC-3). RESULTS: The presence of high-affinity binding sites for NPY was shown on PC-3 cells (radioreceptor assay). Reverse transcription-polymerase chain reaction analysis indicated that these sites correspond to the Y1 and Y2 receptor isoforms. A Y1 receptor protein (70 kDa) was also detected in PC-3 cell extracts by Western blot analysis. The activation of these receptors by NPY resulted in a reduction of forskolin-induced cAMP accumulation and an increase of [Ca2+]i. Moreover, a prolonged treatment with NPY induced a dose-related proliferation of PC-3 cells. CONCLUSIONS: By showing that NPY receptors are expressed in the androgen-independent cell line PC-3 and that their activation results in cell proliferation, the present date suggest that NPY-related mechanisms might be relevant in certain stages of CaP, such as the progression of the disease during the androgen-independent stage. PMID- 11762348 TI - Deregulation of genetic pathways in neuroendocrine tumors. AB - Complexity and redundancy of functional pathways controlled by the human genome explain that a single type of tumor can be induced by independant defective mutations in various genes that encode proteins acting in different parts of the cell physiology. Neuroendocrine tumors represent a powerful model for understanding such a complexity from the fact that at least six unrelated genetic syndromes have been characterized in the last decade which predispose to endocrine cell proliferation with variable penetrance and expressivity. Multiple Endocrine Neoplasia, von Hippel-Lindau. Carney and uncommonly Recklinghausen and Tuberous Sclerosis syndromes represent almost the whole panel of genetic diseases for which genes have been cloned and most of the functional knowledge has been collected. All the endocrine glands are concerned in these diseases, but the cellular pathways that are deregulated downstream from the deleterious mutations occurring in the genes of these autosomal dominant syndromes. might be related to each step of the cell life, from mitosis to DNA transcription, membrane receptor signalling and growth factor production, protein catabolism and extracellular matrix synthesis, and from transcription regulation to apoptosis and response to hypoxia and cellular stress. Here, we present an overview of genes involved in genetic predisposition to neuroendocrine tumors and highlight the complexity of pathways involved and the need of further studies focussing on genes involved in tumoral progression, most neuroendocrine tumors being benign at initial diagnosis but able to produce highly malignant cellular clones related to secondary genetic alterations or deregulation of growth factor production or cell cell adhesion processes. PMID- 11762349 TI - Somatostatin receptor subtype expression in human tumors. AB - The presence of functional SSR in tumors has several clinical implications which include the possibility a) to control hormonal hypersecretion and related symptomatology by treatment with SS-analogs, b) to detect SSR positive tumors and their metastases by in vivo SSR scintigraphy, and c) to carry out SSR-targeted radiotherapy using radiolabeled SS-analogs. The majority of SSR positive tumors show a differential expression of somatostatin receptor subtypes, sst2 receptors being the most frequently expressed SSR subtype. The predominant expression of sst2 receptors forms the basis for the successful application of sst2 preferring agonists in the treatment of patients with GH-secreting pituitary adenomas, as well as in patients with carcinoid or islet cell tumors. Sst2 and sst5 receptors appear to be differentially involved in the regulation of normal and tumoral pituitary hormone secretion. Additionally, sst2 receptors are involved in the receptor-mediated internalisation of sst2 preferring radiolabeled SS-analogs. The predominant expression of sst2 receptors in neuroendocrine tumors probably determines the successful application of radio-labeled SS-analogs for the detection of primary tumors and their metastases by SSR scintigraphy. In conclusion, the efficacy of treatment with SS-analogs, the visualisation of SSR positive tumors, as well as the possibility to carry out SSR-targeted radiotherapy, may very well depend upon the density and subtype of SSR that is expressed by the tumors. Therefore, the characterisation of SSR subtypes in human tumors may have important clinical consequences. PMID- 11762350 TI - Biological relevance of oxytocin and oxytocin receptors in cancer cells and primary tumors. AB - For a long time, the hypothalamic nonapeptide oxytocin (OT) is known to play a crucial role in many reproductive and behavioral functions. In recent years, a new biological effect of OT has been identified in neoplastic pathology. In this context, OT acts as a growth regulator. through the activation of specific G coupled transmembrane receptors (OTR). In vitro, an antiproliferative effect of OT was demonstrated in neoplastic cells of either epithelial (mammary and endometrial) or nervous or bone origin, all expressing OTR. Furthermore, the growth-inhibiting effect of OT was also tested and confirmed in mouse and rat mammary carcinomas in vivo. In neoplastic cells from another OT target tissue, trophoblast, the OT effect was to promote proliferation, the opposite of what previously observed in all the other neoplastic OT responsive cells. The signal transduction involved in the OT biological effect was different in OT growth inhibited or growth-stimulated cells. In the former, the OT effect was mediated by the activation of the cAMP-PKA pathway, a non-conventional OT signaling, whereas in the latter by the increase of intracellular calcium and tyrosine phosphorylation, which are the 'classical' OT transducers. The unexpected role of OT (and OT analogues) in regulating cell proliferation, as well as the diffuse expression of OTR in neoplastic tissue of different origin, open new perspectives on the biological role of the OT-OTR system in cancer. PMID- 11762352 TI - The value of radiolabelled MIBG and octreotide in the diagnosis and management of neuroendocrine tumours. AB - Neuroendocrine tumours have a particular tendency to express functional receptors and/or uptake mechanisms. Radionuclides, such as 123I-MIBG, which is taken up by a specific uptake mechanism, and 111In-pentetreotide, which binds to somatostatin receptors, present an imaging modality based on these physiological characteristics rather on purely anatomical alterations. They have been successfully utilised for both the diagnosis and staging of neuroendocrine tumours, as they can identify lesions beyond the diagnostic sensitivity of conventional imaging modalities. Scintigraphy with 111In-pentetreotide is in general more sensitive but scintigraphy with 123I-MIBG may occasionally demonstrate lesions not evident with 111In-pentetreotide. Although both are effective in identifying hepatic metastases there may be quantitative and qualitative differences in the pattern of uptake. 131I-MIBG therapy, based on a positive 123I-MIBG scan, produces symptomatic and hormonal improvement and moderate tumour regression/stabilisation in many patients with metastatic neuroendocrine tumours with minimal adverse effects. It may be a valuable alternative or additional therapeutic option to the currently available conventional treatment modalities. Although experience with 90Y-DOTA-D-Phe1-Tyr3 octreotide therapy is still limited, preliminary studies have demonstrated useful activity in tumours with positive 111In-pentetreotide scans, and yet other radionuclide analogues may become available. However, treatment with the combination of both radionuclides is another therapeutic possibility. PMID- 11762351 TI - Comparative somatostatin receptor scintigraphy using in-111-DOTA-lanreotide and in-111-DOTA-Tyr3-octreotide versus F-18-FDG-PET for evaluation of somatostatin receptor-mediated radionuclide therapy. AB - BACKGROUND: Based on the high number of somatostatin (SST) receptors expressed by neuroendocrine tumors, long-acting SST analogs have been successfully used for tumor detection. New developments point to the potential use of these types of radioligands for tumor-specific radionuclide therapy. PATIENTS AND METHODS: We have comparatively investigated the diagnostic capacity of the SST analog. 111In DOTA-lanreotide (LAN), as opposed to 111ln-DOTA-DPhe1-Tyr3-octreotide (TOCT) in tumor patients. This article gives an overview of recent scintigraphic results compared to CT/MRI, 18F-FDG-PET, endoscopy and/or surgery in a threshold of 218 tumor patients. RESULTS: As opposed to radiology, previously unknown tumor lesions were demonstrable by either SST radioligand in about one third of patients. In carcinoid patients, the SST scan sensitivity was 64% for LAN (18 of 28) and 87% (34 of 39) for TOCT, whereas the sensitivity was 100% in patients with (radioiodine-negative) thyroid cancer (17 of 17) for LAN and 95% for TOCT (20 of 21). Discordant scintigraphic results between LAN and TOCT (higher tumor uptake and/or visualisation of different lesions in the same patient) were also seen in patients with lymphoma, lung cancer and intestinal adenocarcinoma. In a direct comparison of both SST tracers in 38 tumor patients, LAN gave positive results in 35 of 38, TOCT in 36 of 38 and 18F-FDG-PET in 14 of 22 of the same patients. SST scan results obtained by both tracers were equivocal in 23 of 38 patients, but were better in 10 patients withTOCTand in 5 patients with LAN. CONCLUSIONS: We conclude that both SST radioligands are suitable tracers for tumor imaging, but may give significantly different uptake results for different tumor types. Since the uptake is most important for tumor therapy, using either longacting SSTanalogs, and/or 90Y-labeled analogs, careful evaluation should be made prior to therapy. PMID- 11762353 TI - Nuclear medicine imaging of neuroendocrine tumours. AB - Different tracers have been proposed in nuclear medicine to visualize neuroendocrine tumours: the majority are based on specific uptake mechanisms while some are aspecific. Among the most important gamma-emitting tracers, radiolabelled metaiodobenzylguanidine (123I or 121I-MIBG) and 111In-pentetreotide should be mentioned. In particular. good results can be obtained with 111In pentetreotide scanning, which visualizes more than 70% of all neuroendocrine tumours and in some indications, as in gastro-entero-pancreatic (GEP) tumours, has a diagnostic sensitivity superior to that of conventional radiological imaging. Radiolabelled monoclonal antibodies have at present only a storical value, while a series of new peptides represent interesting subjects in areas currently being regarded. Positron emission tomography (PET) is a successful modality to detect cancer and recent years, has demonstrated a great diagnostic value in a large series of tumour types. 18F-deoxyglucose (FDG)-PET has also been used to diagnose tumours of neuroendocrine origin. Even if 18F-FDG has been successfully and widely employed in oncology, it has not demostrated a significant uptake in well differentiated neuroendocrine tissues. On the contrary, other positron emitter tracers seem to be more promising. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. This uptake seems to be selective and some clinical evidence has demonstrated that it allows the detection of more lesions with PET than with CT or octreotide scintigraphy. Another radiopharmaceutical in development for PET is 11C L-DOPA, which seems to be useful in visualizing endocrine pancreatic tumours. This Review summarizes the potential of several nuclear medicine techniques in the diagnosis of neuroendocrine tumours and stresses the renewed role of nuclear -medicine in the management of this disease. PMID- 11762354 TI - The gut as the largest endocrine organ in the body. AB - Secretin, gastrin and cholecystokinin were the first discovered gut hormones. Today we recognize more than 30 gut hormone genes and a multitude of bioactive peptides, which make the gut the largest endocrine organ in the body. Due to structural homologies gut peptide hormones/growth factors have been divided into separate families. It has been emphasized that those peptides are widely distributed, but have a specific expression in different cell types. The intestine can also be regarded as a sensory organ operating via neurons, endocrine cells and immune cells with gut peptides as signalling substances. Expression studies of peptide receptors in gut neuroendocrine tumours in combination with tailored peptide analogs have been helpful in developing new diagnostic and therapeutic strategies. New fields of research will relate to gut peptides associated with deficiency diseases and as potential growth factors in malignancies. Enterochromaffin cells, interspersed throughout the entire gastrointestinal mucosa, form the largest endocrine cell system. The physiological role of hormonal messengers, peptide receptors and amine transporters is currently under investigation as well as their potential involvement in disease, e.g. the secretory diarrhea associated with midgut carcinoid tumours. PMID- 11762355 TI - Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. AB - BACKGROUND: Tumour marker measurement gives clinicians useful information for the follow-up and management of patients with neuroendocrine tumours (NETs). The currently used tumour markers for NETs are neuron-specific enolase (NSE) and chromogranin A (CgA). The clinical accuracy of these biomarkers depends on histotype and disease extent. CgA is thought to be the optimal marker for most NETs, as it is independent of the biological characteristics of the tumour. AIM OF THE STUDY: In this study we investigated the value of CgA assessment with respect to the other biomarkers in the diagnosis and follow-up of patients with different types of NETs. PATIENTS AIND METHODS: We measured CgA, NSE, carcinoembryonic antigen (CEA) and urine 5-hydroxy-3-indoleacetic acid (5-HIAA) in 290 patients with 127 gastroenteropancreatic (GEP) tumours, 49 neuroblastomas, 36 lung tumours, 24 medullary thyroid carcinomas (MTCs). 15 pNETs, 12 paragangliomas. 7 Merkel's cell carcinomas (MCCs) and 20 NETs of unknown origin. CgA and 5-HIAA were quantitated by immunoenzymatic assays, while NSE and CEA were determined by radioimmunoassays. RESULTS: The biomarkers' specificity in GEP tumours was 86% for CgA, 100% for NSE, 91% for CEA and 100% for 5-HIAA. The corresponding sensitivity was 68% for CgA, 33% for NSE, 15.4% for CEA and 35% for 5-HIAA. The sensitivity of CgA largely depends on disease extent or presence of functioning tumours and is highest in metastatic and syndromic patients. CgA determination in GEP tumour monitoring is useful to evaluate the response to therapy and to follow up patients with liver metastases. In neuroblastomas the overall specificity of NSE and CgA was 50%, and 83%, respectively. In these tumours NSE sensitivity was close to 90% in all clinical stages, while the sensitivity of CgA depended on clinical stage (50% for stage I and II, 60% for stage III and 100% for stage IV tumours). Also in this type of tumour changes in CgA levels correlated with objective response. In paragangliomas CgA measurement may provide useful clinical information. Measurement of CgA is of use in the diagnosis of lung carcinoids, while its value in MTCs, pNETs and MCCs is very limited. CONCLUSIONS: CgA was confirmed to be the best tumour marker currently available for identifying patients suffering from NETs of the GEP system, lung carcinoids and neuroblastomas. CgA evaluation is recommended in the follow-up of patients with such tumours. PMID- 11762356 TI - Circulating chromogranin A in the assessment of patients with neuroendocrine tumours. A single institution experience. AB - BACKGROUND: Chromogranin A (CgA) is a secretory protein present in dense-core vesicles of neuroendocrine (NE) cells. Its ubiquitous presence in NE tissues makes it a suitable circulating marker of neoplasms of NE origin. PATIENTS AND METHODS: Plasma CgA was determined in 178 patients with NE tumors and in 36 patients with non-endocrine malignancies. Circulating CgA was also serially evaluated in 39 NE cancer patients with advanced disease submitted to systemic therapy and in 14 patients with no evidence of disease (NED). RESULTS: Supranormal CgA values were found in 81% of patients with advanced NE tumors and in only 91% of NED cases. Plasma CgA in patients with well differentiated NE tumors, such as carcinoids, carcinoma of gastrointestinal tract, pheocromocytoma, pancreatic NE carcinoma (either functioning or not functioning), medullary thyroid carcinoma and NE tumors from various primary sites, was higher and more frequently elevated than in patients with small-cell lung cancer (P < 0.001). Plasma CgA did not discriminate patients with NE from those with non NE neoplasms since it was found elevated in 44% of the latter cases. Plasma CgA pattern correlated with the disease response in patients submitted to cytotoxic treatment and with changes in clinical symptomathology in patients receiving somatostatin analogs. CONCLUSIONS: Our data confirm that CgA is the best circulating neuroendocrine marker available up to now available for the management of differentiated neuroendocrine malignancies irrespective of tumor location and functional status. CgA plasma levels could also identify the coexistence of neuroendocrine differentiation in the context of non-endocrine malignancies. Circulating CgA seems to be less useful in undifferentiated tumors such as small cell lung cancer. PMID- 11762357 TI - Impact of chromogranin A measurement in the work-up of neuroendocrine tumors. AB - Since the development of the first immunoassay for circulating chromogranin A in 1984, a lot of studies have evaluated its clinical impact in neuroendocrine tumors. Initially studied in pheochromocytoma patients, the clinical impact of chromogranin A has rapidly extended to most neuroendocrine tumours, sometimes in combination with other eutopic or ectopic secretions. In our experience, CgA demonstrates a variable sensitivity between NET primary and a high specificity. Our results suggest that CgA should be routinely screened in foregut-derived NET and abandoned in the routine screening of medullary thyroid carcinoma. In addition, in phaeochromocytoma and ileum-NET patients, CgA demonstrates a comparable sensitivity with urinary reference markers and its impact on the follow-up will form a key point when recommending routine screening. Both tumor burden and secretory activity should be taken into account when interpreting CgA results. PMID- 11762358 TI - Ectopic ACTH syndrome: molecular bases and clinical heterogeneity. AB - There are roughly two types of ectopic ACTH syndrome (EAS). one associated with overt malignancies and one with occult neoplasms. The prototype of the first condition is Cushing's syndrome sustained by small-cell lung cancer (SCLC), while bronchial carcinoid tumors are the most common occult sources of ACTH. Patients with EAS and SCLC may have an atypical presentation with muscle wasting and weight loss that are more frequently observed than the classic cushingoid features. These patients have a poor prognosis because SCLC associated with the EAS is more resistant to chemotherapy and the severe hypercortisolism is responsible for a high rate of life-threatening complications during treatment. Conversely, the clinical and biochemical features of the EAS associated with carcinoid may overlap those seen in pituitary-dependent Cushing's syndrome. An extensive radiological and hormonal work-up is necessary to detect the extrapituitary source of ACTH. However, the differentiation between the pituitary, or eutopic, from the non-pituitary, or ectopic, source of ACTH secretion may be extremely difficult in some cases despite the wide diagnostic armamentarium available. Molecular biology studies have demonstrated that the carcinoid cells achieve a process of corticotroph differentiation being able to express the proopiomelanocortin (POMC) gene and to process POMC correctly to release large amounts of intact ACTH. Conversely, SCLC processes POMC in an aberrant way releasing high concentrations of ACTH precursors and less intact ACTH in the circulation. PMID- 11762359 TI - Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. AB - The aim of this article is to briefly review the physiology of growth hormone releasing hormone (GHRH) and the diagnosis and treatment of GHRH-mediated acromegaly. Moreover, the role of GHRH and its antagonists in the pathogenesis and treatment of cancer will be reviewed. Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. GHRH-producing neurons have been well characterized in the hypothalamus by immunostaining techniques. Hypothalamic tumors, including hamartomas. choristomas, gliomas. and gangliocitomas. may produce excessive GHRH with subsequent GH hypersecretion and resultant acromegaly. GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation and increased GH secretion. The structure of hypothalamic GHRH was infact elucidated from material extracted from pancreatic GHRH-secreting tumors in two patients with acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small-cell lung cancers, adrenal adenomas, and pheochromocitomas which have been reported to secrete GHRH. Acromegaly in these patients. however, is uncommon. In a retrospective survey of 177 acromegalic patients only a single patient was identified with elevated plasma GHRH levels. Measuring GHRH plasma levels therefore provides a precise and cost-effective test for the diagnosis of ectopic acromegaly. Peripheral GHRH levels are not elevated in patients with hypothalamic GHRH- secreting tumors, supporting the notion that excess eutopic hypothalamic GHRH secretion into the hypophyseal portal system does not appreciably enter the systemic circulation. Elevated circulating GHRH levels, a normal or small-size pituitary gland, or clinical and biochemical features of other tumors known to be associated with extrapituitary acromegaly, are all indications for extrapituitary imaging. An enlarged pituitary is, however, often found on MRI of patients with peripheral GHRH-secreting tumors, and the radiologic diagnosis of a pituitary adenoma may be difficult to exclude. Surgical resection of the tumor secreting ectopic GHRH should reverse the hypersecretion of GH, and pituitary surgery should not be necessary in these patients. Nonresectable, disseminated or reccurrent carcinoid syndrome with ectopic GHRH secretion can also be managed medically with long-acting somatostatin analogs (octreotide and lanreotide). The presence of GHRH and its receptors in several extrahypothalamic tissues, including ovary, testis and the digestive tract, suggests that GHRH may have a regulatory role in these tissues. As previously mentioned, biologically or immunologically active GHRH and mRNA encoding GHRH have been found in several human malignant tumors. including cancers of the breast, endometrium and ovary and their cell lines. The synthesis and evaluation of analogs with various modifications revealed that certain hydrophobic and helix-stabilizing amino acid substitutions can produce antagonists with increased GH releasing inhibitory potencies and GHRH receptor-binding affinities in vitro. The review of experimental results of these substances are promising altrough no clinical data are yet available. Finally, the advent of these antagonists has allowed significant progress in the understanding of the role of the central and tissue GHRH-GH-IGFs system in the pathogenesis of tumors. PMID- 11762360 TI - Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. AB - Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS). PMID- 11762361 TI - [XVII Brazilian Congress of Clinical Neurophysiology and XXVI Meeting of the Brazilian Epilepsy League. Recife, October 10-13, 2001. Abstracts]. PMID- 11762362 TI - Royal Institute of Public Health and Hygiene and Society of Public Health. Evidence submitted to the Health Committee. PMID- 11762363 TI - [History of the grafting of coronary artery bypass]. AB - Great efforts had been made to treat coronary artery disease by using myocardial revascularization for a century. Evolved from the early exploration, and the early forms of direct revascularization. The grafting of coronary artery bypass began in the 1960s. Big progresses had been made in the operative technique, the grafting materials of bypass and myocardial protection etc. in the following forty years. Now it is one of the most effective therapies for coronary artery disease. PMID- 11762364 TI - [Claude Bernard, founder of experimental physiology]. AB - Claude Bernard was a famous French physiologist and philosopher in the 19th century. His experimental researches almost involved all fields of physiology. It is generally recognized by physiologists that in the research of Bernard in the digestion of pancreas, glucogenesis in the liver, and the vasomotor mechanism and the mechanism of action of curari and carbon monoxide were all at the lead. His researches established the foundation for modern physiology, modern biochemistry and the works of Pavlov, and were the initiation of experimental physiology. PMID- 11762365 TI - [Influence of Adam Schall's changing calendar on Yun - qi theory in the early Qing Dynasty]. AB - The Yun - qi theory is closely related to the calendar system. In Chinese history, the change of the calendar system by Adam Schall von Bell in early Qing Dynasty was a disputable event. Studying its effect on Yun - qi theory, we find out the issue of changing the order of Zi and Shen lunar mansions, which annoyed many Chinese astronomers and scholars, had no significant influence on Yun - qi theory. As for the new calculation system of clepsydra and solar terms, these changes increased the accuracy of the Yun - qi calendar. PMID- 11762366 TI - [Influence of art of changes on the thinking of traditional Chinese medicine]. AB - The most important influence of art of changes on traditional Chinese medicine (TCM) was reflected in the formation of the basic theory of TCM. Some innovations were achieved by using the theory of art of changes to research medicine in later ages. However, the specific therapies and the prognostication of diseases inferred by using the art of mathematics were mostly unreliable. Though the researches on the art of changes were helpful to the exploration of the cause and effect of TMC, yet, its practical significance should be evaluated properly. PMID- 11762367 TI - [Research on the school of Danxi of the Ming dynasty]. AB - Zhu Danxi, the founder of Danxi School, one of the four major schools of the Jin Yuan dynasties, was famous for its Yin - nourishing theory. Clinically, it was adept in treating miscellaneous disorders, with the "four - injury theory" as its theory for differentiation of Zheng. The medical thinking of Danxi is quite specific that it exerted its clinical and academic influence mostly in the Ming dynasty, with so many schools followed him. Though research on its origin and evolution, direct followers like Dai Sigong, Wang Lu, Lin Chung et al. not only totally inherited Danxi's medical idea, but also became the receiver of his academic experiences. Indirect followers(study perronally) reached its peak in the Ming dynasty. They inherited Danxi's experience and further developed to supplement his theory. For other physicians partly following Danxi's experience also emerged and applied his academy for further development of medical theory. PMID- 11762368 TI - [Research on the headstream of Yu Yue's thought of abolishing traditional Chinese medicine]. AB - Yu Yue was a famous scholar in the Qing dynasty, who studied traditional Chinese medicine (TCM) by himself. However, he was the first one that suggested the abolishing of TCM in modern times. His unfortunate individual experience and the influence of his times that he lived can both helped us to explain his different attitude towards TCM in different periods. PMID- 11762369 TI - [Pictures of channel system in Isimpo (Prescriptions of medical heart]. AB - Pictures of channel system in Isimpo (Prescriptions of Medical Heart) was the earliest illustrations of channels. It was of important reference value for the researches on the running courses of channels, confirmation of some points, including Sanyinjiao, Dadu, Taibai and Gongsun, and its orders etc. PMID- 11762370 TI - [Bo tuo, a study on the reasons of its denomination]. AB - Research is made on the reasons of Bo tuo's denomination by studying its got - up method and the evolution of these two characters' font, in order to get a more rational commentary. Discussion is made on each variant forms of Bo tu, so as to explain the reasons of the variation. PMID- 11762371 TI - [Brief history of cosmetology in the imperial palace of China]. AB - The development of Chinese Palace's cosmetology is divided into three periods. It is in its embryonic stage that from the Xia to the Western Jin. The drugs and perfumes related to cosmetology were taken seriously by the Palace. The formulation of facial beauty was established. From the Eastern Jin to the end of Tang Dynasty was the forming periods. Cosmetology has been fully developed, and became the physical civilization which could enjoy by both nobels and common people. The developing and enriching time was from the Wu Dai to the end of the Qing Dynasty. The theory of cosmetology achieved a great development. The number of prescriptions of the Palace's cosmetology were increased greatly. PMID- 11762372 TI - [The manufacturing of penicillin in China in 1940s]. AB - A small modernized factory was established in early 1947, and developed into industrialized production. The manufacture of penicillin in China in the 1940s lay down the foundation for the industrialized production of penicillin in China which occupies an important position in the medical history of China. PMID- 11762373 TI - [Review on the Newly complied four - volume: a general history of Chinese medicine]. PMID- 11762374 TI - Arthromitus (Bacillus cereus) symbionts in the cockroach Blaberus giganteus: dietary influences on bacterial development and population density. AB - The filamentous spore-forming bacterium Arthromitus, discovered in termites, millipedes, sow bugs and other soil-dwelling arthropods by Leidy (1850), is the intestinal stage of Bacillus cereus. We extend the range of Arthromitus habitats to include the hindgut of Blaberus giganteus, the large tropical American cockroach. The occurrence and morphology of the intestinal form of the bacillus were compared in individual cockroaches (n=24) placed on four different diet regimes: diurnally maintained insects fed (1) dog food, (2) soy protein only, (3)purified cellulose only, and (4) a dog food-fed group maintained in continuous darkness. Food quality exerted strong influence on population densities and developmental stages of the filamentous bacterium and on fecal pellet composition. The most dramatic rise in Arthromitus populations, defined as the spore-forming filament intestinal stage, occurred in adult cockroaches kept in the dark on a dog food diet. Limited intake of cellulose or protein alone reduced both the frequency of Arthromitus filaments and the rate of weight gain of the insects. Spores isolated from termites, sow bugs, cockroaches and moths, grown on various hard surfaces display a branching mobility and resistance to antibiotics characteristic to group I Bacilli whose members include B. cereus, B. circulans, B. alvei and B. macerans. DNA isolated from pure cultures of these bacilli taken from the guts of Blaberus giganteus (cockroach), Junonia coenia (moth), Porcellio scaber (sow bug) and Cryptotermes brevis (termite) and subjected to Southern hybridization with a 23S-5S B. subtilis ribosomal sequence probe verified that they are indistinguishable from laboratory strains of Bacillus cereus. PMID- 11762375 TI - Exploring Earth's oldest geological record in Greenland. PMID- 11762376 TI - The cytoskeleton: problems, paradigms, and prospects. PMID- 11762377 TI - The efficacy of RNAi in the study of the plant cytoskeleton. AB - Recent studies on a variety of organisms point to the ubiquity of RNA interference (RNAi) as a means to induce a gene-specific block to translation. RNAi has gained popularity in the last few years in the study of a number of problems in development. In this review, we highlight recent findings with RNAi using several different kinds of animals and fungi, and we show how these responses parallel cosuppression effects described in plants nearly a decade earlier. We then point to the efficacy of RNAi in studying minor and regulatory components of the plant cytoskeleton, and we highlight some recent studies using this approach with the water fern, Marsilea vestita. PMID- 11762378 TI - Maintenance of asymmetric cellular localization of an auxin transport protein through interaction with the actin cytoskeleton. AB - In shoots, polar auxin transport is basipetal (that is, from the shoot apex toward the base) and is driven by the basal localization of the auxin efflux carrier complex. The focus of this article is to summarize the experiments that have examined how the asymmetric distribution of this protein complex is controlled and the significance of this polar distribution. Experimental evidence suggests that asymmetries in the auxin efflux carrier may be established through localized secretion of Golgi vesicles, whereas an attachment of a subunit of the efflux carrier to the actin cytoskeleton may maintain this localization. In addition, the idea that this localization of the efflux carrier may control both the polarity of auxin movement and more globally regulate developmental polarity is explored. Finally, evidence indicating that the gravity vector controls auxin transport polarity is summarized and possible mechanisms for the environmentally induced changes in auxin transport polarity are discussed. PMID- 11762379 TI - Halogenated auxins affect microtubules and root elongation in Lactuca sativa. AB - We studied the effect of 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA), a recently described root growth stimulator, and 5,6-dichloro-indole-3-acetic acid (DCIAA) on growth and microtubule (MT) organization in roots of Lactuca sativa L. DCIAA and indole-3-butyric acid (IBA) inhibited root elongation and depolymerized MTs in the cortex of the elongation zone, inhibited the elongation of stele cells, and promoted xylem maturation. Both auxins caused the plane of cell division to shift from anticlinal to periclinal. In contrast, TFIBA (100 micromolar) promoted elongation of primary roots by 40% and stimulated the elongation of lateral roots, even in the presence of IBA, the microtubular inhibitors oryzalin and taxol, or the auxin transport inhibitor naphthylphthalamic acid. However, TFIBA inhibited the formation of lateral root primordia. Immunostaining showed that TFIBA stabilized MTs orientation perpendicular to the root axis, doubled the cortical cell length, but delayed xylem maturation. The data indicate that the auxin-induced inhibition of elongation and swelling of roots results from reoriented phragmoplasts, the destabilization of MTs in elongating cells, and promotion of vessel formation. In contrast, TFIBA induced promotion of root elongation by enhancing cell length, prolonging transverse MT orientation, delaying cell and xylem maturation. PMID- 11762381 TI - Modeling human pilot cue utilization with applications to simulator fidelity assessment. AB - An analytical investigation to model the manner in which pilots perceive and utilize visual, proprioceptive, and vestibular cues in a ground-based flight simulator was undertaken. Data from a NASA Ames Research Center vertical motion simulator study of a simple, single-degree-of-freedom rotorcraft bob-up/down maneuver were employed in the investigation. The study was part of a larger research effort that has the creation of a methodology for determining flight simulator fidelity requirements as its ultimate goal. The study utilized a closed loop feedback structure of the pilot/simulator system that included the pilot, the cockpit inceptor, the dynamics of the simulated vehicle, and the motion system. With the exception of time delays that accrued in visual scene production in the simulator, visual scene effects were not included in this study. Pilot/vehicle analysis and fuzzy-inference identification were employed to study the changes in fidelity that occurred as the characteristics of the motion system were varied over five configurations. The data from three of the five pilots who participated in the experimental study were analyzed in the fuzzy-inference identification. Results indicate that both the analytical pilot/vehicle analysis and the fuzzy-inference identification can be used to identify changes in simulator fidelity for the task examined. PMID- 11762380 TI - Cortical actin filaments potentially interact with cortical microtubules in regulating polarity of cell expansion in primary roots of maize (Zea mays L.). AB - Evidence is accumulating implicating cortical microtubules in the directional control of cell expansion. However, the role of actin filaments in this process is still uncertain. To determine the involvement of actin in cell elongation, the organization of actin filaments in primary roots of maize (Zea mays L.) was examined by use of an improved fluorochrome-conjugated phalloidin-labeling method. With this method, a previously undetected state of actin organization was revealed in the elongation and maturation zone of maize roots. Fine transversely oriented cortical actin was observed in all cells of the elongation zone, including the epidermis, cortex, and vascular tissues. The orientation of cortical actin shifted from a predominantly transverse orientation to oblique, longitudinal, and/or random arrangements as the cells matured. The reorientation of cortical actin in maturing root cells mimics the behavior of cortical microtubules reported in other studies. Furthermore, roots treated with the microtubule-stabilizing drug taxol improved the quality of actin preservation as evidenced by the thicker bundles of cortical actin. This suggested that taxol was also capable of stabilizing the cortical actin networks. The elongation of roots exposed to 1 micromole Latrunculin B, an actin-disrupting drug, was inhibited, and after 24 h the roots exhibited moderate swelling particularly along the elongation zone. Latrunculin B also caused microtubules to reorient from transverse to oblique arrays. The results from this study provide evidence that cortical microtubules and actin filaments respond in a coordinated way to environmental signals and may well depend on both elements of the cytoskeleton. PMID- 11762382 TI - Iodate and iodide effects on iodine uptake and partitioning in rice (Oryza sativa L.) grown in solution culture. AB - In the Xinjiang province of western China, conventional methods of iodine (I) supplementation (i.e, goiter pills and iodinated salt) used to mitigate I deficiencies were ineffectual. However, the recent addition of KIO3 to irrigation waters has proven effective. This study was conducted to determine the effects of I form and concentration on rice (Oryza sativa L.) growth, I partitioning within the plant, and ultimately to assist in establishing guidelines for incorporating I into the human food chain. We compared IO3- vs. I- in order to determine how these chemical species differ in their biological effects. Rice was grown in 48 L aerated tubs containing nutrient solution and IO3- or I- at 0, 1, 10, or 100 micromoles concentrations (approximately 0, 0.1, 1, and 10 mg kg-1 I). The IO3- at 1 and 10 micromoles had no effect on biomass yields, and the 100 micromole treatment had a small negative effect. The I- at 10 and 100 micromoles was detrimental to biomass yields. The IO3- treatments had more I partitioning to the roots (56%) on average than did the I- treatments (36%), suggesting differences in uptake or translocation between I forms. The data support the theory that IO3- is electrochemically or biologically reduced to I- prior to plant uptake. None of the treatments provided sufficient I in the seed to meet human dietary requirements. The I concentration found in straw at 100 micromoles IO3- was several times greater than seed, and could provide an indirect source of dietary I via livestock feeding on the straw. PMID- 11762383 TI - Revisions to Healthy People 2000 baselines. PMID- 11762384 TI - Direct standardization (age-adjusted death rates). PMID- 11762385 TI - Years of healthy life. PMID- 11762386 TI - Evaluating public health data systems: a practical approach. PMID- 11762387 TI - Health status indicators: differentials by race and Hispanic origin. PMID- 11762388 TI - Muscle sympathetic nerve activity (MSNA) after 120 days of 6 degrees head-down bed rest (HDBR). AB - The alterations in the sympathetic nervous system are commonly seen after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR). Several studies have examined the effect of HDBR for a few days or a weeks on the vasomotor sympathetic tone at rest. However, it remains unclear how a long-lasting (>50 days) HDBR affects resting vasomotor sympathetic nervous activity. Consequently, we measured muscle sympathetic nerve activity (MSNA) in six healthy male volunteers (range, 26-42 years) in a resting supine position before and after 60 and 120 days of HDBR. MSNA was measured directly from the tibial nerve using a microneurographic technique. Resting supine MSNA significantly increased after 60 (28.2 +/- 2.7 bursts/min) and 120 (29.4 +/- 4.2 bursts/min) days of HDBR compared with the pre-HDBR level (19.0 +/- 2.3 bursts/min). Heart rate was significantly higher after 60 (73 +/- 2 beats/min) and 120 (72 +/- 3 beats/min) days of HDBR than before (65 +/- 2 beats/min). In contrast, mean blood pressure remained unchanged during and after 120 days of HDBR. In conclusion, the resting vasomotor sympathetic tone increased after long lasting simulated microgravity. PMID- 11762389 TI - A multiple chamber, semicontinuous, crop carbon dioxide exchange system: design, calibration, and data interpretation. AB - Long-term, whole crop CO2 exchange measurements can be used to study factors affecting crop growth. These factors include daily carbon gain, cumulative carbon gain, and carbon use efficiency, which cannot be determined from short-term measurements. We describe a system that measures semicontinuously crop CO2 exchange in 10 chambers over a period of weeks or months. Exchange of CO2 in every chamber can be measured at 5 min intervals. The system was designed to be placed inside a growth chamber, with additional environmental control provided by the individual gas exchange chambers. The system was calibrated by generating CO2 from NaHCO3 inside the chambers, which indicated that accuracy of the measurements was good (102% and 98% recovery for two separate photosynthesis systems). Since the systems measure net photosynthesis (P-net, positive) and dark respiration(R-dark, negative), the data can be used to estimate gross photosynthesis, daily carbon gain, cumulative carbon gain, and carbon use efficiency. Continuous whole-crop measurements are a valuable tool that complements leaf photosynthesis measurements. Multiple chambers allow for replication and comparison among several environmental or cultural treatments that may affect crop growth. Example data from a 2 week study with petunia (Petunia x hybrida Hort. Vilm.-Andr.) are presented to illustrate some of the capabilities of this system. PMID- 11762390 TI - Medicare and Medicaid programs; hospital Conditions of Participation: anesthesia services. Final rule. AB - This final rule amends the Anesthesia Services Condition of Participation (CoP) for hospitals, the Surgical Services Condition of Participation for Critical Access Hospitals (CAH), and the Surgical Services Condition of Coverage for Ambulatory Surgical Centers (ASCs), and, with its publication, withdraws the January 18, 2001 final rule (66 FR 4674).This final rule maintains the current physician supervision requirement for certified registered nurse anesthetists(CRNAs), unless the Governor of a State, in consultation with the State's Boards of Medicine and Nursing, exercises the option of exemption from this requirement consistent with State law. PMID- 11762391 TI - Protection of human research subjects. Final rule. AB - The Department of Health and Human Services (DHHS) is withdrawing Subpart B of its human subjects protection regulations published on January 17, 2001 and is issuing this replacement rule. These regulations provide additional protections for pregnant women and human fetuses involved in research. The final rule continues the special protections for pregnant women and human fetuses that have existed since 1975 and makes limited changes in terminology referring to neonates, clarifies provisions for paternal consent when research is conducted involving fetuses, clarifies language that applies to research on newborns of uncertain viability, and corrects technical errors. PMID- 11762392 TI - Disaster unemployment assistance program. Interim final rule; request for comments. AB - The Employment and Training Administration (ETA) of the Department of Labor (Department) is issuing this interim final rule, effective upon publication, to clarify eligibility for disaster unemployment assistance (DUA) in the wake of the major disasters declared as a result of the terrorist attacks of September 11, 2001. To provide an opportunity for public participation in this emergency rulemaking, this interim final rule includes a post-publication comment period. The Department will publish a final rule after taking into account any comments that are received. PMID- 11762393 TI - Gamma-irradiated onions as a biological indicator of radiation dose. AB - Post-irradiation identification and dose estimation are required to assess the radiation-induced effects on living things in any nuclear emergency. In this study, radiation-induced morphological/cytological changes i.e., number of root formation and its length, shooting length, reduction in mitotic index, micronuclei formation and chromosomal aberrations in the root tip cells of gamma irradiated onions at lower doses (50-2000 cGy) are reported. The capabilities of this biological species to store the radiation-induced information are also studied. PMID- 11762395 TI - Mary Ellen Jones: December 25, 1922-August 23, 1996. PMID- 11762394 TI - Jordi Folch-Pi: March 25, 1911-October 3, 1979. PMID- 11762396 TI - Hans Joachim Muller-Eberhard: May 5, 1927-March 3, 1998. PMID- 11762397 TI - Daniel Nathans: October 30, 1928-November 16, 1999. PMID- 11762398 TI - Howard M. Temin: December 10, 1934-February 9, 1994. PMID- 11762399 TI - Benton J. Underwood: February 28, 1915-November 29, 1994. PMID- 11762400 TI - Julius H. Comroe, Jr.: March 13, 1911-July 31, 1984. PMID- 11762402 TI - Is there a veterinary papyrus of Kahun? PMID- 11762401 TI - Rafael Lorente De No: April 8, 1902 - Alruk 2, 1990. PMID- 11762403 TI - Available sources of veterinary biographies useful in compiling contributions for an International Dictionary of Veterinary Biography(IDVB). AB - In the framework of the WAHVM-project to compile an International Dictionary of Veterinary Biography, two modern tools are described that may assist the contributors to this dictionary in finding references concerning the persons of their choice. The first is the World Biographical Index (WBI), an initiative of K. G. Saur Publishing, that can be consulted in print and online as well. The index covers more than 5000 sources of biographical information of all times and regions of the world. Its 7th online-edition (www.biblio.tu-bs/de/wbi) identifies the works where information can be found on the lives of 4551 veterinarians, for the greater part of the past. The editions are regularly expanded. The second tool is a CD-ROM, published by the WAHVM, with 13.000 references to books, periodical articles and dissertations on veterinary history. More than 40% of these references have biographical relevance. The index on personal names contains more than 2700 names. Both tools are complementary because the source materials differ largely. PMID- 11762404 TI - Food on foot: long-distance trade in slaughter oxen between Denmark and the Netherlands (14th-18th century). AB - This paper presents a short review of the long-distance trade in slaughter oxen in Northwest Europe. The long-term development of the trade is described against the social-economic background of the production and consumption areas. In the 14th century, the Danes obtained the right to sell cattle in certain Dutch cities. From 1500 onwards, the export of oxen from Denmark and the adjacent duchy of Schleswig-Holstein increased considerably. The export reached its peak in the first quarter of the 17th century; registered export in 1612 amounted to more than 52.000 oxen over land and, in 1624, about 10.000 oxen over sea. Part of that export was destined for the Dutch market. Protectionist tax measures taken by the Dutch government and the outbreaks of rinderpest put an end to the regular ox trade in the first half of the 18th century. By decree, local authorities tried to prevent the spread of contagious animal diseases. The history of international cattle trade and hauling, however, indicates that economic motives largely outweighed animal welfare issues. Thus, in addition to addressing the logistics of the trade, this paper also addresses veterinary aspects and animal welfare issues related to the transport of cattle. PMID- 11762405 TI - A selection of the publications written or edited by Ivan Katic. PMID- 11762406 TI - Ivan Katic: his importance for the history of Danish veterinary medicine and the Danish Society for the History of Veterinary Medicine. PMID- 11762407 TI - Ivan Katic and the Danish Veterinary and Agricultural Library (DVJB). PMID- 11762408 TI - Photo report dedicated to Ivan Katic. PMID- 11762409 TI - Harnessing the power of antibodies for therapeutic applications was a question of time. PMID- 11762410 TI - Non-Hodgkin's lymphoma: review of conventional treatments. AB - The non-Hodgkin's lymphomas are a diverse groups of lymphoid neoplasms that collectively rank fifth in cancer incidence and mortality. Conventional treatment for patients with newly-diagnosed non-Hodgkin's lymphoma (NHL) includes radiation or chemotherapy. In addition, those with asymptomatic low-grade disease may follow a "watch and wait" approach. Single agent oral alkylating therapy and CVP (cyclophosphamide, vincristine, and prednisone) have become a mainstay of treatment for low-grade NHL. High intensity chemotherapy consisting of the anthracycline, doxorubicin along with cyclophosphamide, vincristine and prednisone (CHOP) is offered as standard treatment for intermediate-grade NHL. Following relapse, salvage therapy rarely results in long-term survival in patients with low-grade NHL. Up to 50% of patients die within five years of first relapse. For patients with intermediate-grade NHL who relapse after or do not respond to first-line treatment, a range of combination regimens can be offered, composed of non-cross resistant drugs not typically used during first-line treatment. However, less than half of patients with intermediate-grade disease achieve prolonged disease-free survival. With today's' conventional treatments, cure is only a possibility for a minority of patients with intermediate-grade disease and a limited group of patients with indolent NHL who are diagnosed at early stages. Novel approaches to treatment are therefore needed. Monoclonal antibodies may fulfill this need, administered either as single agents or in conjunction with conventional cytotoxic approaches. The task now lies in determining how best to use this new modality, with the hope of bringing a cure to a greater number of patients. PMID- 11762411 TI - The history and rationale for monoclonal antibodies in the treatment of hematologic malignancy. AB - The potential of antibodies as "magic bullets" for cancer therapy has been appreciated for nearly a century. During the past 25 years, various scientific developments have made possible the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies (MoAbs). Intact, unconjugated MoAbs may: [1] produce anticancer effects through the immune system on the basis of interactions between the Fc portion of antibody and complement proteins and/or effector cells; [2] induce regulatory effects by neutralizing circulating ligands or blocking cell membrane receptors, thereby interfering with ligand/receptor interactions and signal transduction; [3] serve as immunogens for anti-cancer vaccines through the anti-idiotype-network cascade. Conjugated MoAbs can serve as carriers of other agents such as radioisotopes, natural toxins, chemotherapy drugs, cytokines, and immune cells. Important aspects of the antigenic target are the degree to which it is tumor-specific or tumor-associated, whether it internalizes or not, whether it is shed, the density of expression, and the physiologic significance of the antigen to the target cell. The clinical foundation for antibody-mediated therapy was laid in the 1980s when investigators established the safety of antibody administration, defined certain predictable antibody-mediated toxicities, and confirmed that antibodies could reach tumor targets and produce antitumor effects. A major limitation of these early mouse monoclonal antibodies was overcome with the production of antibodies with varying degrees of humanization. In 1997 rituximab (Rituxan), a mouse-human chimeric anti-CD20, became the first MoAb approved by regulatory agencies for the treatment of a human malignancy. PMID- 11762412 TI - Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma. AB - Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results. PMID- 11762413 TI - Toxin-labeled monoclonal antibodies. AB - To arm monoclonal antibodies (MAbs) with the power to kill malignant cells, they have been connected to toxins to create chimeric proteins called immunotoxins. Conventional immunotoxins contain a MAb chemically conjugated to a toxin which is mutated or chemically modified to minimize binding to normal cells. Examples include anti-B4-blocked ricin, targeting CD5, and RFB4-deglycosylated ricin A chain, targeting CD22. Conventional immunotoxins are capable of inducing responses in patients with hematologic malignancies, with dose-limiting toxicities being vascular leak syndrome, thrombocytopenia, and hepatic damage. Newer immunotoxins contain a recombinant ligand, either the variable domains (Fv) of a MAb, or a growth factor, fused to a truncated bacterial toxin. Bacterial toxins commonly used for this purpose include diphtheria toxin and Pseudomonas exotoxin. DAB389lL2 (Ontak) is a recently approved growth factor fusion toxin containing human interleukin-2 and diphtheria toxin and is effective in chemotherapy-resistant cutaneous T-cell lymphoma. Anti-Tac(Fv)-PE38 (LMB-2) and RFB4(dsFv)-PE38 (BL22) are two recombinant immunotoxins, targeting CD25 and CD22, respectively, in which Fvs of MAbs targeting these antigens are fused to truncated Pseudomonas exotoxin. Both LMB-2 and BL22 have exhibited clinical activity in patients with hematologic malignancies, with less vascular leak syndrome and probably less immunogenicity than the larger conventional immunotoxin conjugates. New recombinant immunotoxins are currently being engineered and developed to target other hematologic and solid tumor antigens. PMID- 11762414 TI - Radioimmunotherapy of B-cell NHL. AB - Much progress has been made in the development and implementation of radionuclide carrying antibody therapy (radioimmunotherapy or RIT) of non-Hodgkin's lymphomas (NHL) in the past decade. Response rates have generally exceeded 60% for nonmyeloablative single dose RIT (85% - 100% for myeloablative) in patients who have relapsed after primary therapy. It is also encouraging that the duration of such responses has often been greater than the response to the last chemotherapeutic regimen administered. These results, as well as a favorable toxicity profile, have resulted in the successful earlier and more widespread use of this new therapeutic modality. Although unlabeled antibody therapy alone has had a positive impact on the treatment of NHL, the response rates for RIT have been higher than (sometimes nearly double) those for unlabeled antibody therapy. This has been demonstrated in trials that have directly compared radiolabeled antibody with unlabeled antibody, as well as in separate trials for similar patient groups. Use of radionuclides in conjunction with antibodies adds transient marrow suppression and a small risk of second malignancy over unlabeled antibody therapy. However, the toxicity from a single course of RIT is very favorable compared to chemotherapy. Despite the enormous progress of RIT, much remains to be learned to fully optimize the role of this exciting modality in the treatment of NHL. PMID- 11762415 TI - Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin's lymphoma. AB - Zevalin (ibritumomab tiuxetan, IDEC-Y2B8) is a murine IgG1 kappa monoclonal antibody conjugated to tiuxetan (MXDTPA) that chelates Yttrium or Indium and is directed against the CD 20 molecules of B lymphocytes. Phase I studies have determined the optimal dose of pretreatment rituximab to be 250 mg/m2 seven days prior and immediately prior to the administration of Zevalin. Phase I/II data have determined the dose of 0.4 mCi/kg to be the maximum tolerated dose (MTD) for patients with platelet counts > 150,000 and < 25% bone marrow involvement with NHL. The dose of 0.3 mCi/kg is the MTD in patients with platelet counts between 100,000-149,000. Toxicity is primarily hematologic, transient, and reversible. Dosimetry has been completed using 111In-2B8. Results to date demonstrate that, at the above doses, no patients exceeded the protocol-prescribed organ maximum dose of 2,000 cGy or red marrow maximum dose of 300 cGy. Therefore, future use will not require pretreatment dosimetry. Zevalin contains a pure beta-emitting isotope; no protective patient or staff isolation procedures are required. A randomized Phase III trial has been completed, comparing Zevalin with a standard dose of rituximab (375 mg/m2 q week for four weeks) in patients with relapsed indolent or follicular transformed NHL. The overall response rate (ORR) was 80% in the Zevalin arm compared to 56% (p = 0.002) in the rituximab arm. The CR was 30% vs. 16% (p=0.04). A nonrandomized trial in patients refractory to rituximab demonstrated an ORR of 74% and a CR rate of 15%. A Phase II study of a reduced dose of Zevalin in patients with mild thrombocytopenia demonstrated an ORR of 67% and a 33% CR rate. Zevalin is safe and effective in patients with relapsed or refractory NHL, even in patients refractory to prior rituximab therapy. PMID- 11762416 TI - Monoclonal antibodies in the treatment of hematologic malignancies: radiation dosimetry aspects. AB - A number of therapeutic agents in nuclear medicine are currently attracting considerable interest, including several for the treatment of hematologic and nonhematologic malignancies. A knowledge of the radiation dose received by different organs in the body is essential to the optimization of the therapy for each patient; one wants to maximize the dose to the malignant tissue while minimizing the dose to critical healthy tissues and avoiding any toxic response therein. In this paper, current methods for calculating radiation doses will be discussed and evaluated. In almost all nuclear medicine therapy, and particularly in this application, dose to the active marrow is of paramount concern. Specific focus on current bone marrow dose models and their ability to predict observed marrow toxicity in patient populations to date will be discussed. The paper will focus on current and possible future dosimetry practice in therapeutic nuclear medicine, particularly as regards the treatment of hematologic malignancies. PMID- 11762417 TI - Antibody therapy of acute and chronic leukemias. AB - The development of antibody-based therapies for the treatment of both acute and chronic leukemias have undoubtedly been one of the most important advances in the treatment of leukemia. The importance of these novel agents lies not only in their unique mechanisms of action, but also their improved side effect profile which allows patients of advanced age or with significant co-morbid medical conditions to receive potentially beneficial therapies. Advances in therapeutic applications of monoclonal antibodies have come from a greater understanding of the biological characteristics of the antibody, as well as the target antigen, both of which impact the potential efficacy of a particular antibody. In the following review we will discuss the clinical development and potential roles of monoclonal antibodies in the treatment of both acute and chronic leukemias. PMID- 11762418 TI - Future approaches for treating hematologic disease. AB - The approval of monoclonal antibodies for therapy of hematologic malignacies (Rituxan, Mylotarg, Campath) renewed the interest in antibodies as potential new treatment options for cancer patients. Antibodies are effective in inhibiting tumor cell growth , inducing apoptosis, and activating host effector mechanisms for tumor cell killing. Monoclonal antibodies can be clinically effective as monotherapy, as targeting agents delivering either potent cytotoxic drugs or radionuclides as well as in combination with conventional chemotherapies. Advances in antibody engineering provided new capabilities to reduce immunogenicity, alter half life, increase effector functions, and increase tumor targeting for optimal therapeutic modalities requiring chronic dosing regimens. During the next decade, as new tumor-specific surface antigens are discovered and the linkage between genes and function is better understood, new targets will be identified for regulating tumor cell growth by engineered antibodies with agonist or antagonist activity. Additionally, antibody engineering will allow for more efficient radionuclide or cytotoxic drug targeting or lead to more selective activation of relevant host effector mechanisms, leading to a safe and effective therapy of cancer. PMID- 11762419 TI - [Clinical usefulness of selected factors in cervix mucous of women treated for infertility]. PMID- 11762421 TI - Opportunity knocked. PMID- 11762420 TI - Key industry facts. PMID- 11762422 TI - [Case study--relationship between prevalence of shyness, social phobia and avoidant personality in male sexual disorders]. AB - Social phobia, avoidant personality disorder and shyness are very akin disorders, despite the fact that the first two are mental disorders, whereas the third is found mainly in lay or psychological literature. The relationship between these disorders and male sexual disorders can only be hypothesized from clinical studies and psychopathological theories. Social phobia, avoidant personality disorder, and shyness, share a probable indirect responsibility in sexual disorders because they impair the ability of subjects to meet partners. There are only a few direct studies of the negative impact of shyness on sexual behavior. OBJECTIVE: The objective of this study was to compare males with sexual disorders to non-sexual disorder males on diagnosis of social phobia, avoidant personality disorder and shyness. METHODS: We conducted a case-control study comparing a group of male patients seeking care for sexual disorders (n = 87) and a control group of male subjects without sexual disorder (n = 87), regarding the diagnosis of social phobia, avoidant personality disorder and shyness. Diagnoses were appreciated with a structured diagnostic interview (CIDI for the diagnosis of social phobia) or a list of criteria (DSM IV criteria for avoidant personality disorder) and through standardized scales (Fear Questionnaire, CBSHY, Cottraux male sexual problems questionnaire). Severity of shyness was evaluated through visual analog scales. RESULTS: We found strong significant statistical differences between cases and controls regarding the percentage in each group of social phobia, avoidant personality disorder and shyness. For shyness, the mean score at CBSHY was 16.2 (+/- 12.63) for the cases and 6.07 (+/- 6.67) for the controls (p < 0.0001), whereas the percentage of cases with a score of > 19.5 was 41.4% vs 6.9% for the controls (p < 0.001); 27.6% of the cases had a CIDI diagnosis of social phobia vs 8% of the controls (p < 0.001); 31% of the cases implemented DSM IV criteria for the diagnosis of avoidant personality disorder vs 6.9% of the cases (p < 0.001). CONCLUSION: Our results are in favor of one or several factors in common between social phobia, avoidant personality disorder and shyness, which would be strongly related to male sexual disorders. PMID- 11762423 TI - Cognitive reactivity to sad mood: structure and validity of a new measure. AB - Cognitive reactivity to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The present report describes the development and test of a questionnaire that aims to measure cognitive reactivity independently from a mood induction procedure. The Leiden Index of Depression Sensitivity (LEIDS) was filled out by 198 participants. After Principal Components Analysis, 26 items were retained, which comprised four factors with good psychometric properties: Negative Self-Evaluation; Acceptance/Coping; Indifference; and Harm Avoidance. In a sample of 48 college students, LEIDS scores--particularly Negative Self-Evaluation and Harm Avoidance--were rather strong predictors of cognitive reactivity in a mood induction procedure. In contrast, baseline depression and baseline cognitive dysfunction did not predict cognitive reactivity. It is concluded that the LEIDS is a promising measure of cognitive reactivity, and that clinical studies need to be carried out to test its ability to predict relapse of depression. PMID- 11762424 TI - Comorbid anxiety and mood disorders among persons with social anxiety disorder. AB - Axis I comorbidity is associated with greater severity of social anxiety disorder. However, the differential effects of comorbid mood and anxiety disorders on symptom severity or treatment outcome have not been investigated. We evaluated 69 persons with uncomplicated social anxiety disorder, 39 persons with an additional anxiety disorder, and 33 persons with an additional mood disorder (with or without additional anxiety disorders). Those with comorbid mood disorders reported greater duration of social anxiety than those with uncomplicated social anxiety disorder. They were also judged, before and after 12 weeks of cognitive-behavioral group treatment and at follow-up, to be more severely impaired than those with no comorbid diagnosis. In contrast, persons with comorbid anxiety disorders were rated as more impaired than those with no comorbid diagnosis on only a single measure. Type of comorbid diagnosis did not result in differential rates of improvement of social anxiety disorder. PMID- 11762425 TI - Physiological and psychological reactivity in women with asthma: the effects of anxiety and menstrual cycle phase. AB - The relation between menstrual cycle timing, panic attacks, and diagnosis of asthma was explored in this study. Women with or without asthma and with or without a history of panic attacks engaged in a psychophysiological task during either the intermenstrual or premenstrual cycle phase and completed self-report measures of menstrual symptoms and attitudes, general psychological symptoms, and attitudes toward illness. No significant differences were identified for psychological or psychophysiological measures with menstrual cycle phase as a factor. However, women with both asthma and a history of panic attacks reported more general psychological distress than women in the other groups, and more state anxiety than controls. Women in the asthma, asthma and panic, and panic groups reported higher anxiety sensitivity than the control group. After listening to asthma-related scenes, women with asthma exhibited a decrease in peak expiratory air flow, and women with asthma and panic exhibited increased skin conductance response magnitude. Implications for the role of anxiety in lung function are discussed, as well as directions for future research with asthma and anxiety populations. PMID- 11762426 TI - The connection between cognitive development and specific fears and worries in normal children and children with below-average intellectual abilities: a preliminary study. AB - The present study explored the relationship between cognitive development and anxiety phenomena in 4-12-year-old children. Fears and worries of normal children (n=176) were compared to those of children with below-average intellectual abilities (children with BAIA; n=105). We evaluated to what extent level of cognitive development as indexed by a Piagetian conservation task was associated with the presence of fears and worries. While normal children and children with BAIA did not differ with regard to the content of their fears and worries, normal children more frequently reported such anxiety phenomena during the semi structured Anxiety Interview than did children with BAIA. Furthermore, in normal children, evidence was found to suggest that level of cognitive development contributes to the experience of fears and worries. That is, anxiety phenomena were more prevalent among those children who passed a Piagetian conservation task. However, when anxiety phenomena were assessed by means of the Koala Fear Questionnaire (KFQ), a different picture emerged. KFQ data suggested that fears were less frequent in normal children and those children with BAIA who had a higher level of cognitive functioning. Apparently, the Anxiety Interview and the KFQ tap quite different aspects of anxiety. The KFQ seems to measure primitive fears that are likely to be prevalent among children with limited cognitive capacity, whereas the Anxiety Interview assesses more sophisticated anxiety phenomena that probably depend on high levels of cognitive functioning. PMID- 11762427 TI - Thought suppression: specificity in agoraphobia versus broad impairment in social phobia? AB - The paradoxical effects of intended thought suppression have been linked to psychological disorders, specifically anxiety disorders. So far, the evidence for thought suppression playing a major role in the disorder is mixed. One important issue is whether thought suppression is impaired only for thoughts related to the disorder, or if the ability for mental control is generally impaired in anxiety patients. This study compared groups of agoraphobics and social phobics with a healthy control group. All subjects were asked to suppress two topics related to the respective central fear of the two disorders and one nonspecific topic. We found a rather specific deficit in thought suppression for the agoraphobics; that is, when compared with the control group, we found the biggest differences for the agoraphobic fear. The social phobics seem to be characterized by a general impairment of mental control, affecting specific and nonspecific stimuli. In addition, among several psychopathological variables, social anxiety proved to be the strongest predictor for problems with thought suppression. Taken together, there are several indicators that generally impaired thought suppression may be an important feature of social phobia. PMID- 11762428 TI - Antidepressant discontinuation in the context of cognitive behavioral treatment for panic disorder. AB - Cognitive behavioral treatment (CBT) has been shown to reduce risk for adverse reactions (e.g., rebound panic) following benzodiazepine taper for patients with panic disorder (PD). This study evaluated the effects of antidepressant discontinuation for patients with PD in the context of CBT. Patients with PD (n=21) on a stable dose of antidepressants completed a 12-week group CBT treatment and were randomly assigned to discontinue antidepressants during week 8 of the treatment. There were no statistically significant differences between groups at posttreatment or 6-month follow-up. Data indicate no apparent immediate or long-term adverse effects for antidepressant discontinuation for patients with PD receiving CBT. PMID- 11762429 TI - Insomniacs' reported use of CBT components and relationship to long-term clinical outcome. AB - Although there is considerable evidence for the efficacy of non-pharmacological treatment of insomnia, many of the larger trials have delivered CBT in multicomponent format. This makes it impossible to identify critical ingredients responsible for improvement. Furthermore, compliance with home implementation is difficult to ascertain in psychological therapies, and even more so when trying to differentiate across a range of elements. In the present report, 90 patients who had completed 12 month follow-up after participation in a clinical effectiveness study of CBT in general medical practice, responded to a questionnaire asking them about their use of the ten components of the programme. Reports of home use were then entered as predictors of clinical response to treatment. Results indicated that reported home use of stimulus control/sleep restriction was the best predictor of clinical improvement in sleep latency and nighttime wakefulness. Cognitive restructuring also contributed significantly to reduction in wakefulness. In spite of being the most highly endorsed component (by 79% of respondents) use of relaxation did not predict improvement on any variable. Similarly, sleep hygiene was unrelated to sleep pattern change and use of imagery training was modestly predictive of poor response in terms of sleep latency. There are methodological limitations to this type of post hoc analysis, nevertheless, these results being derived from a large patient outcome series raise important issues both for research and clinical practice. PMID- 11762430 TI - The ionic layer is required for efficient dissociation of the SNARE complex by alpha-SNAP and NSF. AB - The four-helical bundle soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complex that mediates intracellular membrane fusion events contains a highly conserved ionic layer at the center of an otherwise hydrophobic core. This layer has an undetermined function; it consists of glutamine (Q) residues in syntaxin and the two synaptosomal-associated protein of 25 kDa (SNAP-25) family helices, and an arginine (R) in vesicle-associated membrane protein (a 3Q:1R ratio). Here, we show that the ionic-layer glutamine of syntaxin is required for efficient alpha-SNAP and NSF-mediated dissociation of the complex. When this residue is mutated, the SNARE complex still binds to alpha SNAP and NSF and is released through ATP hydrolysis by NSF, but the complex no longer dissociates into SNARE monomers. Thus, one function of the ionic layer--in particular, the glutamine of syntaxin--is to couple ATP hydrolysis by NSF to the dissociation of the fusion complex. We propose that alpha-SNAP and NSF drive conformational changes at the ionic layer through specific interactions with the syntaxin glutamine, resulting in the dissociation of the SNARE complex. PMID- 11762431 TI - Rapid formation of the stable tyrosyl radical in photosystem II. AB - Two symmetrically positioned redox active tyrosine residues are present in the photosystem II (PSII) reaction center. One of them, TyrZ, is oxidized in the ns micros time scale by P680+ and reduced rapidly (micros to ms) by electrons from the Mn complex. The other one, TyrD, is stable in its oxidized form and seems to play no direct role in enzyme function. Here, we have studied electron donation from these tyrosines to the chlorophyll cation (P680+) in Mn-depleted PSII from plants and cyanobacteria. In particular, a mutant lacking TyrZ was used to investigate electron donation from TyrD. By using EPR and time-resolved absorption spectroscopy, we show that reduced TyrD is capable of donating an electron to P680+ with t1/2 approximately equal to 190 ns at pH 8.5 in approximately half of the centers. This rate is approximately 10(5) times faster than was previously thought and similar to the TyrZ donation rate in Mn-depleted wild-type PSII (pH 8.5). Some earlier arguments put forward to rationalize the supposedly slow electron donation from TyrD (compared with that from TyrZ) can be reassessed. At pH 6.5, TyrZ (t1/2 = 2-10 micros) donates much faster to P680+ than does TyrD (t1/2 > 150 micros). These different rates may reflect the different fates of the proton released from the respective tyrosines upon oxidation. The rapid rate of electron donation from TyrD requires at least partial localization of P680+ on the chlorophyll (PD2) that is located on the D2 side of the reaction center. PMID- 11762432 TI - On death and Dworkin: a critique of his theory of inviolability. PMID- 11762433 TI - Monitoring air quality in Healthy People 2000. PMID- 11762434 TI - [Measures against rabies in Hungary in the 18th and 19th centuries]. AB - The author presents a concise overview of the royal prescriptions and methods of popular medicine on the fighting of rabies in Hungary during the 18th and 19th century. PMID- 11762435 TI - [The Cheiron emblem and Cheiron medal of the World Association for the History of Veterinary Medicine]. AB - In 1964 the first symposium on history of veterinary medicine was organised in Hanover by the section "History of Veterinary Medicine" of the German Society of Veterinary Medicine. During the 6th symposium in Hanover the World Association for the History of Veterinary Medicine (WAHVM) was created. In the following years further symposiums, called later on congresses took place almost every year. In 2001 the 32nd congress will be held. The Association gave herself in 1973 a distinguishing mark, the Cheiron Emblem. Sixteen years later, the Cheiron Medal was endowed to allow the World Association to express thanks and acknowledgement for special achievements in the field of history of veterinary medicine. The Cheiron Medal was bestowed for the first time on May 26th, 1989. PMID- 11762436 TI - [Armourer and mad cow disease: images of veterinarians in music]. AB - This contribution is not about animals in music; it rather attempts to describe how veterinary medicine as a discipline and veterinarians as representatives of the profession are perceived of and portrayed in music. Aside from Gioacchino Rossini's "Barber of Seville", in which Count Almaviva impersonates a veterinarian of the day, the most sympathetic veterinarian character ever created by a lyricist or composer in surely Hans Stadinger, the "armourer" and vet in Albert Lortzings opera. In other musical genres such as artsongs and folksongs, the only such figure worthy of musical interpretation seems to have been those masters of the fiery forge who were also wise in the veterinary healing arts. In the past 20 years vets and veterinary medicine have been included in new musical trends: There are musicals and radio plays in which even the youngest members of the audience are exposed to the veterinarian profession. A number of pop groups are also to be mentioned here. For example, animal welfare has been thematized by punk rockers, and a pop group for Hamburg has put a medieval horse blessing to music. Last but not least, a number of vets in Berlin turn their everyday troubles and worries into musical parodies. PMID- 11762437 TI - [Belgian memorials to animals wounded and killed in war]. AB - Compassion is a feeling that makes man sensitive to the suffering and the death of animals. This feeling is not always shared by men and frequently they forget to recognize the merits of the animals wounded or killed while fighting side by side. In the past the horses were even more exposed to the dangers of war than men. In Belgium marks of these sufferings can be found on some monuments as well as in awards added to high military decorations. PMID- 11762438 TI - Ion transport in roots: measurement of fluxes using ion-selective microelectrodes to characterize transporter function. AB - The transport of mineral ions into and out of tissues and cells is central to the life of plants. Ion transport and the plasma membrane transporters themselves have been studied using a variety of techniques. In the last 15 years, measurement of specific ion fluxes has contributed to the characterization of transport systems. Progress in molecular genetics is allowing gene identification and controlled expression of transporter molecules. However the molecular expression of transporter gene products must be characterized at the functional level. The ion-selective microelectrode technique to measure specific ion fluxes non-invasively is ideally suited to this purpose. This technique, its theory, its links with others and its application and prospects in plant science, are discussed. Ions studied include hydrogen, potassium, sodium, ammonium, calcium, chloride and nitrate. Applications discussed include: solute ion uptake by roots; gravitropism and other processes in the root cap, meristematic and elongation zones; Nod factor effect on root hairs; osmotic and salt stresses; oscillations; the effects of light and temperature. Studies have included intact roots, leaf mesophyll and other tissues, protoplasts and bacterial biofilms. A multi-ion capability of the technique will greatly assist functional genomics, particularly when coupled with imaging techniques, patch clamping and the use of suitable mutants. PMID- 11762439 TI - On the relation between personality and job performance of airline pilots. AB - The validity of a personality questionnaire for the prediction of job success of airline pilots is compared to validities of a simulator checkflight and of flying experience data. During selection, 274 pilots applying for employment with a European charter airline were examined with a multidimensional personality questionnaire (Temperature Structure Scales; TSS). Additionally, the applicants were graded in a simulator checkflight. On the basis of training records, the pilots were classified as performing at standard or below standard after about 3 years of employment in the hiring company. In a multiple-regression model, this dichotomous criterion for job success can be predicted with 73.8% accuracy through the simulator checkflight and flying experience prior to employment. By adding the personality questionnaire to the regression equation, the number of correct classifications increases to 79.3%. On average, successful pilots score substantially higher on interpersonal scales and lower on emotional scales of the TSS. PMID- 11762440 TI - Effect of different gravity environments on DNA fragmentation and cell death in Kalanchoe leaves. AB - Different gravity environments have been shown to significantly affect leaf plantlet formation and asexual reproduction in Kalanchoe daigremontiana Ham. and Perr. In the present work, we investigated the effect of gravity at tissue and cell levels. Leaves and leaf-plantlets were cultured for different periods of time (min to 15 d) in different levels of gravity stimulation: simulated hypogravity (1 rpm clinostats; 2 x 10(-4) g), 1 g (control) and hypergravity (centrifugation; 20 and 150 g). Both simulated hypogravity and hypergravity affected cell death (apoptosis) in this species, and variations in the number of cells showing DNA fragmentation directly correlated with nitric oxide (NO) formation. Apoptosis in leaves was more common as gravity increased. Apoptotic cells were localized in the epidermis, mainly guard cells, in leaf parenchyma, and in tracheary elements undergoing terminal differentiation. Exposures to acute hypergravity (up to 60 min) showed that chloroplast DNA fragmentation occurred prior to nuclear DNA fragmentation, marginalization of chromatin, nuclear condensation, and nuclear blebbing. Addition of sodium nitroprusside (NO donor) mimicked centrifugation. NO and DNA fragmentation decreased with N(G)-monomethyl L-arginine (NO-synthase inhibitor). The variations in NO levels, nucleoid DNA fragmentation, and cell death show how chloroplasts, cells and leaves may respond (and adapt) to gravity changes. PMID- 11762441 TI - Crew tension during a space station simulation. AB - Two space simulation studies for the European Space Agency found that interpersonal tension increased in the beginning, around the middle, and toward the end of the confinement. This article reports data from a third study where this issue was further examined. Three subjects were confined in the MIR space station simulator in Moscow for 135 days. Communication analysis, peer rating, questionnaires, and interviews were used to assess crew tension. The temporal pattern found in this study corresponds to the previous findings. The beginning of the period was characterized by competition over leadership. Decreased crew cohesion and aggression toward the mission control marked the middle of the confinement. In the final weeks, open conflicts emerged, and one member was socially excluded. Joking occurred frequently in the first half of the confinement, whereas negative emotional expressions increased in the second half. These results might assist planners in anticipating behavioral problems during space missions. PMID- 11762442 TI - Selecting pilots with crew resource management skills. AB - For years, pilot selection has focused primarily on the identification of individuals with superior flying skills and abilities. More recently, the aviation community has become increasingly aware that successful completion of a flight or mission requires not only flying skills but the ability to work well in a crew situation. This project involved development and validation of a crew resource management (CRM) skills test for Air Force transport pilots. A significant relation was found between the CRM skills test and behavior-based ratings of aircraft commander CRM performance, and the implications of these findings for CRM-based selection and training are discussed. PMID- 11762443 TI - A closed-loop system for examining psychophysiological measures for adaptive task allocation. AB - A closed-loop system was evaluated for its efficacy in using psychophysiological indexes to moderate workload. Participants were asked to perform either 1 or 3 tasks from the Multiattribute Task Battery and complete the NASA Task Load Index after each trial. An electroencephalogram (EEG) was sampled continuously while they performed the tasks, and an EEG index (beta/alpha plus theta) was derived. The system made allocation decisions as a function of the level of operator engagement based on the value of the EEG index. The results of the study demonstrated that it was possible to moderate an operator's level of engagement through a closed-loop system driven by the operator's own EEG. In addition, the system had a significant impact on behavioral, subjective, and psychophysiological correlates of workload as task load increased. The theoretical and practical implications of these results for adaptive automation are discussed. PMID- 11762444 TI - Genetic privacy and discrimination: a survey of state legislation. Comment. AB - As of January 15, 1999, forty-four states had enacted legislation concerning genetic privacy or discrimination. This Comment catalogs these statutes and tabulates their most salient provisions. PMID- 11762445 TI - Primary adenocarcinoma of the urinary bladder: a study of 6 cases from the pathologist's point of view. AB - OBJECTIVE: The clinical presentation of adenocarcinoma is not different from the usual transitional cell carcinoma, hence the histological diagnosis plays an important role in the interpretation of cystoscopic biopsies. Six cases of primary adenocarcinoma of the urinary bladder are described from the pathologist's point of view. The diagnostic problems encountered in these cases are highlighted. METHODS: 6 cases of primary adenocarcinoma of the urinary bladder were encountered from 1983 to 1997. Relevant clinical data were analyzed. Multiple sections from the tumor and adjoining areas of the bladder were studied. Five patients were aged 50 to 75 years and the youngest patient was 22 years old. RESULTS: Hematuria and retention of urine were common presenting symptoms. Histologically, the diagnostic problems faced were mucinous metaplasia vs mucinous carcinoma, clear cell adenocarcinoma of the urinary bladder vs clear cell carcinoma of the pelvic kidney. We had one case of urachal and 5 cases of non-urachal carcinoma. CONCLUSIONS: Primary adenocarcinoma of the urinary bladder is an unusual tumor accounting for 0.5 to 2% of all bladder malignancies. They are commonly seen in endemic areas like schistosomiasis. By origin they are grouped into urachal and non-urachal carcinoma and histologically grouped as enteric, mucinous, clear cell and adenocarcinoma not otherwise specified. Direct consultation with the urologist, clinical findings, investigations and careful screening of histological material will help the pathologist to arrive at a correct diagnosis. PMID- 11762446 TI - Hydrous pyrolysis of polycyclic aromatic hydrocarbons and implications for the origin of PAH in hydrothermal petroleum. AB - Polycyclic aromatic hydrocarbons (PAH) are found at high concentrations in thermally altered organic matter and hydrothermally generated petroleum from sediment-covered seafloor hydro-thermal systems. To better understand the factors controlling the occurrence of PAH in thermally altered environments, the reactivities of two PAH, phenanthrene and anthracene, were investigated in hydrothermal experiments. The compounds were heated with water at 330 degrees C in sealed reaction vessels for durations ranging from 1 to 17 days. Iron oxide and sulfide minerals, formic acid, or sodium for-mate were included in some experiments to vary conditions within the reaction vessel. Phenanthrene was unreactive both in water alone and in the presence of minerals for up to 17 days, while anthracene was partially hydrogenated (5-10%) to di- and tetrahydroanthracene. In the presence of 6-21 vol % formic acid, both phenanthrene and anthracene reacted extensively to form hydrogenated and minor methylated derivatives, with the degree of hydrogenation and methylation increasing with the amount of formic acid. Phenanthrene was slightly hydrogenated in sodium formate solutions. The hydrogenation reactions could be readily reversed; heating a mixture of polysaturated phenanthrenes resulted in extensive dehydrogenation (aromatization) after 3 days at 330 degrees C. While the experiments demonstrate that reaction pathways for the hydrogenation of PAH under hydrothermal conditions exist, the reactions apparently require higher concentrations of H2 than are typical of geologic settings. The experiments provide additional evidence that PAH may be generated in hydrothermal systems from progressive aromatization and dealkylation of biologically derived polycyclic precursors such as steroids and terpenoids. Furthermore, the results indicate that PAH initially present in sediments or formed within hydrothermal systems are resistant to further thermal degradation during hydrothermal alteration. PMID- 11762447 TI - Race and the new reproduction. PMID- 11762448 TI - The performance of the human nose in odour measurement. AB - Over the last 20 years or so, there has been steadily increasing activity in the area of applied human odour measurement. This has been especially true outside of the United States. Yet, for about 40 years, there has also been decreasing interest and activity, on the part of academic smell researchers, in rigorous quantitative measurement of the functional properties of the human olfactory system. There are some optimistic signs, however, that this situation may be improving. Applied meetings such as this one are reaching out to learn more about basic research in human olfaction and some research groups are venturing out to indoor air quality, environmental health, water quality and other applied areas. In this paper I hope to support and accelerate the increasingly fruitful interactions that are beginning. The paper aims to make four main points. First, some of the most important ways in which the laboratory differs from everyday life will be noted. Keeping these differences in mind lessens the risk that laboratory data will be used uncritically to make predictions of real-world responses to chemical stimuli. Next, the specific benefits that would accrue from more fruitful interactions between basic and applied researchers will be highlighted; this is perhaps best seen by noting problem areas resulting from too little cross-fertilisation. Third, the CEN standard for the measurement of odour thresholds will be discussed in light of what is known concerning both the functional aspects of the human olfactory system and the current state of knowledge concerning best methods for investigating this system. Finally, some recent work we have done that was designed to help characterise human odour responses and demonstrate improved methodology, will be briefly mentioned. The paper concludes with suggestions as to how the scientific basis of applied odour measurement may best be enhanced. PMID- 11762449 TI - Recent odour regulation developments in Flanders: ambient odour quality standards based on dose-response relationships. AB - Until now there has been little uniformity in the approach of odour nuisance problems in Flanders. A switch to a standardised and scientifically underpinned approach is essential and is currently in full development. This paper mainly discusses the results of five year research on odour concentration standard developments in Flanders, executed in the period 1996-2000. The research was focused on five pilot sectors: pig farms, slaughterhouses, paint spray installations, sewage treatment plants and textile plants. The general approach of the method to determine the dose-response relation was found to be sufficient. The methodology used is fully described in the paper presented by Van Broeck and Van Langenhove at the CIWEM and IAWO Joint International Conference on Control and Prevention of Odours in the Water Industry in September 1999. For each location (16 locations in total) an unambiguous dose-response relation could be derived (rising nuisance for rising concentrations). In most cases, a "no effect" level could be determined. The background percentage nuisance fluctuated between 0 and 15%. For the sectors of the slaughterhouses, paint spray installations and sewage treatment plants a no effect level was 0.5, 2.0 and 0.5 sniffing units m( 3) as 98th percentile (sniffing units are odour concentrations measured by means of sniffing measurements on the field) was determined. For the sectors of the textile plants and pig farms, no unambiguous no effect level was found. Currently research is undertaken to translate the no effect levels to odour standards. Other initiatives, taken to underpin the Flemish odour regulations, such as the development of an odour source inventory and a complaint handling system, are also briefly discussed. PMID- 11762450 TI - Development of odour assessment criteria in New South Wales and application of the criteria for the assessment of a major public works project. AB - The introduction of the forthcoming Australian and New Zealand standard on odour measurement has led to the review of odour regulation in most Australian states. In New South Wales the regulator has drafted an odour impact assessment policy for point source emissions. The policy is based on the new odour measurement standard and defines regulatory dispersion modelling procedures. The New South Wales odour assessment policy was initially drafted on the basis of a literature review and has since been developed in consultation with various industry and government groups, including sewerage authorities. The policy, while still officially regarded as a draft, has already been used as the basis for the assessment of a number of sewerage projects that have been characterised by point source emissions. The application of modelling-based assessment procedures requires careful judgement concerning the selection of input data and close scrutiny on behalf of the assessor. This paper examines the assumptions underlying the development of the New South Wales draft odour assessment policy and draws important universal lessons from its application for the assessment of a major sewerage project. The introduction of peak to mean factors based on one second nose response times has been controversial and alternative procedures are proposed. PMID- 11762451 TI - Directive on odour in ambient air: an established system of odour measurement and odour regulation in Germany. AB - The legal basis for any requirement with respect to ambient air quality is the German Federal Protection Act for Ambient Air. According to article 3 Federal Protection Act all odours caused by plants are defined as an annoyance. The problem is to find out whether an annoyance has to be considered as a significant disturbance. In the Directive on Odour in Ambient Air a complete system is designed, beginning with measurement methods and concluding with ambient air quality requirements. In the following paper the tenor of the Directive on Odour is presented, some main aspects of more than five years of practical experience will be shown and a perspective on some future investigations and developments will be given. As a conclusion it is pointed out that in practice, the Directive on Odours has been successful. Both methods, field measurements with panels and dispersion modelling, are generally qualified for the determination of odour loads. The restriction of odour loads by limit values expressed as odour frequency per year for certain areas has been established in a lot of cases. PMID- 11762452 TI - Removal and decomposition of malodorants by using titanium dioxide photocatalyst supported on fiber activated carbon. AB - Effective and compact deodorization systems have been required for the measure of small-scale emission sources of offensive odors usually found in urban areas. We have developed a sheet material with titanium dioxide (TiO2) photocatalyst supported on fiber activated carbon (FAC) for a compact deodorization system. In the deodorization system using the TiO2/FAC sheet and a ultraviolet lamp, malodorants can be collected on the TiO2/FAC sheet by adsorption and then decomposed by photocatalysis with UV-irradiation. In this study, we obtained basic information about the removal and the decomposition of malodorants in the photocatalytic deodorization system using the TiO2/FAC sheet. The malodorants used in this study were methyl mercaptan, ammonia, and hydrogen sulfide. In addition, two kinds of light sources, a black light bulb (BLB; dominant wavelength: 365 nm) and an ultraviolet germicidal lamp (UV2; dominant wavelength: 254 nm) were used to analyze the effect on removal and decomposition characteristics by different dominant wavelengths. The removal rates of malodorants from the gas phase were determined in the deodorization system in the presence or absence of the TiO2/FAC sheet and UV-irradiation in order to study each removal effect due to adsorption onto the TiO2/FAC sheet, direct photolysis by UV-irradiation, and photocatalytic decomposition. The effect of adsorption onto the TiO2 /FAC sheet was pronounced in this batch-type experiment. The effect of photocatalysis was observed from the removal rates of methyl mercaptan. The percent oxidation of ammonia to nitrate and that of methyl mercaptan to sulfate were examined by determining products, i.e. nitrate and sulfate ions, with purified water after the reaction. The formation of nitrate or sulfate was not observed without UV-irradiation using the BLB, while the reactions progressed in the presence of the TiO2/FAC sheet. When the UV2 lamp was used, the oxidation of methyl mercaptan to sulfate occurred without the TiO2/FAC sheet. This suggests that the decomposition characteristics of malodorants were dependent on the wavelength of the light source. PMID- 11762453 TI - Direct molecular hydrogen sulphide scrubbing with hollowfibre membranes. AB - The emission of hydrogen sulphide is a major problem associated with anaerobic treatment of sulphate and sulphite containing wastewaters. Conventional absorbing processes, such as packed towers, spray towers or bubble columns, are all constrained by factors such as flooding and foaming. Membrane systems, on the other hand, enable independent control of the liquid and gas flow rate and a step change order of magnitude increase in the specific surface area of the contact process. The membrane acts as a gas absorber with a design similar to a shell and tube heat exchanger. On the other hand, they are limited by facets of the membrane such as its resistance to mass transfer and permselectivity, as well as its cost. The work presented in this paper refers to an absorption process based on a non-wetted hollow fibre membrane for the scrubbing of hydrogen sulphide from air, with water as the contact solvent. Results presented describe the performance of the unit in terms of overall transfer and outlet liquid concentration as a function of circulation regime, gas flow rate, liquid flow rate and specific surface area. In particular, results are presented using traditional plots of Sherwood number (Sh) against Graetz (Gr) number for the liquid flowing in the lumens, such that experimental and available empirical descriptions of the process performance are directly compared. Results suggest that, as expected, very efficient mass transfer is obtained. However, the mass transfer was found to reach a maximum value against Gr, contrary to available empirical models. PMID- 11762454 TI - Effect of carvacrol and thymol on odor emissions from livestock wastes. AB - A majority of the beef cattle and swine in the United States is produced in confined facilities. This generates significant environmental pollutants from the waste produced, including global warming gases, odor, and pathogens. The objectives of this study were to control the fermentation activity and pathogens in cattle and swine wastes with antimicrobial plant essential oils. Anaerobic one litre flasks with a working volume of 0.5 l were used to evaluate the effect of carvacrol and thymol on production of fermentation gas, short-chain volatile fatty acids, lactate, and bacterial populations. In cattle waste, 1 g l(-1) each of carvacrol and thymol completely inhibited the production of volatile fatty acids and lactate over 23 days. In swine waste, 2.5 g l(-1) carvacrol inhibited the production of all volatile fatty acids. We conclude that these essential oils are effective in controlling livestock waste odor emissions and field studies are warranted. PMID- 11762455 TI - Improving odour assessment by using better dispersion models: some examples. AB - A critical aspect of odour assessments is modelling to define exposure characteristics in affected communities, and to examine the effects of odour control options. In many cases, odour dispersion is Influenced by complex or non steady-state meteorology that cannot be represented by the commonly used dispersion models, such as ISC3 and AUSPLUME. These models are based on a steady state Gaussian plume assumption, which is often inaccurate. Recent developments in modelling of local meteorology and plume dispersion have enabled far more realistic predictions of odour dispersion. Three-dimensional models have been successfully applied to improve the predictions of odour impact and to better define the parameters for odour control options. These models more accurately represent features such as drainage flows along valley floors and around hills, and strong wind shear that can develop in stable conditions. Such conditions are often critical for a proper assessment of odour impact. Second-by-second fluctuations in odour concentrations can now be simulated using the KSP model developed by Yamartino et al. This model avoids the use of arbritrary methods of determining peak-to-mean ratios. New models can also provide detailed microscale wind fields, suitable for odour modelling in urban areas where odour dispersion is affected by very complex flows. PMID- 11762456 TI - Statistical elements of predicting the impact of a variety of odour sources. AB - Two key elements in predicting odour response are the estimation of peak (few seconds) ground-level concentrations and the evaluation of the likelihood of a consequent adverse response. Peak rather than ensemble-average concentrations are not easily predicted by current dispersion models. The required peak-to-mean ratios depend on source characteristics, downwind distance and atmospheric stability. Using recent wind-tunnel simulations for four types of sources and two atmospheric stabilities and various measures of intermittency and non stationarity, different regimes of behaviour are resolvable. A set of peak-to mean ratios for a specified probability of exceedance is recommended and their practicality discussed. PMID- 11762457 TI - Odour and VOC confining in large enclosures using air curtains. AB - Experiments were conducted on a two stream air-curtain prototype designed for VOC and odour confinement in a truck unloading area. The emphasis was placed on the air supply device. Measurements using tracer gas techniques were performed to assess the effectiveness of the system in terms of air tightness. Leakage flow rate was estimated for various feeding arrangements. Flow visualisations and particle image velocimetry measurements were carried out for a better understanding of the flow dynamics. Evidence was given of the improvements brought by the herein referred to, 'double flux' configuration in comparison to traditional designs. After a brief description of the experimental facility and the basic principle underlying the approach developed, the main results are reported and discussed and recommendations are drawn. Considerations about where the effort will be directed in future works are provided. PMID- 11762458 TI - What are the areas for further research? AB - The introduction of a national standard on odour measurement presents a new challenge for Australian olfactometry laboratories to meet tough new instrumental performance and panellist performance criteria. It also raises issues for end users of olfactometry results. For examples regulatory authorities may need to review the current status of odour regulations and guidelines. The paper reviews major issues pertaining to four components in odour impact assessment: measurement of odour, sampling techniques, air dispersion modelling, and the development of assessment criteria. The paper identifies and discusses the resolution of issues that could have a significant effect on the outcomes of odour impact assessment. It is hoped that the paper will provide a useful guide for industry and environmental protection authorities in the further development of an odour impact assessment procedure. PMID- 11762460 TI - Development of an odorant emission model for sewage treatment works. AB - In the field of odour assessment, much attention has been paid to the measurement of odour concentration. Whilst the concentration of an odour at a receptor is a useful indicator of annoyance, the concentration at the source tells only half the story. The emission rate - the product of odour concentration and air flow rate - is required to appreciate the significance of odour sources. Knowledge of emission rates allows odour sources to be ranked in terms of significance and facilitates appropriate selection and design of odour control units. The emission rate is also a key input for atmospheric dispersion models. Given the increasing importance of odour to sewage treatment works operators, there is a clear need for predictive methods for odour emission rates. Theory suggests that the emission of odorants from sewage to air is controlled by mass transfer resistances in both the gas and liquid phase. These are in turn controlled by odorant and emission source characteristics. The required odorant characteristics are largely known, and mass transfer from many different types of emission sources have been studied. Sewage treatment processes can be described by one or more of six characteristic emission sources, these being quiescent surfaces, channels, weirs and drop structures, diffused aeration, surface aeration and flow over media. This paper describes the development of odorant mass transfer models for these characteristic emission types. The models have been applied in the form of spreadsheet models to the prediction of H2S emissions and the results compared with commercial VOC emission models. PMID- 11762459 TI - Combination of advanced oxidation processes and gas absorption for the treatment of chlorinated solvents in waste gases. AB - Treatment of chlorinated organic compounds in waste gases is difficult because of several reasons: these compounds are dioxin precursors when incinerated, and also biological treatment is difficult because of a limited number of suitable microbial degradation pathways. On the other hand, since the 1990s, a new generation of chemical oxidation techniques has been introduced in water treatment. Advanced Oxidation Processes (AOPs) are based on a combination of UV/H202, UV/O3 or H2O2/O3. The combinations result in the generation of OH radicals, which subsequently attack the organic pollutants. In this work, the treatment of a gas stream (240 L/h) loaded with 20-40 ppmv trichloroethylene (TCE) is presented. Therefore, a combination of an absorption process in a bubble column with a liquid H2O2/O3 initiated oxidation, was investigated. Removal efficiencies, depending on the dosed H2O2 and O3, up to 94% were found. The production of chloride ions was investigated: the Cl-atoms from the removed TCE could be found back as chloride ions. Next to the experimental work, attention was paid to the mechanisms taking place in the proposed concept. Here, a simulation model was developed, considering gas/liquid mass transfer of TCE and ozone, axial liquid dispersion, advective gas and liquid transport and about 29 chemica reaction steps. The modelling allowed a better understanding of the technique and gives insight in its possibilities and limitations. Finally, it can be concluded that the proposed technique shows interesting perspectives: it is able to transform chlorine in chlorinated solvents into chloride ions effectively at ambient temperature conditions. PMID- 11762461 TI - Simultaneous activated sludge wastewater treatment and odour control. AB - Lab-scale tests were used to determine the amount of H2S that can be treated using a range of different activated sludges. Static vessels were used to study the effects of different H2S concentrations (5, 25, 50 and 75 ppm). The data indicated that odour control may be carried out using certain types of sludge, but sludge type, e.g. carbonaceous, nitrifying, with or without coagulant, affects removal efficiency. The presence of the biomass resulted in greater H2S removal than the use of wet scrubbing and the adverse effects on mixed liquor were negligible. A pilot plant was used to study the removal efficiencies of activated sludge diffusion using a typical wastewater treatment plant H2S concentration and investigated the effects that the diffusion of H2S had on the process performance. Results indicated that the levels of H2S produced by other unit processes on a wastewater treatment site (approximately 5 ppm) can be treated using activated sludge diffusion without compromising the performance of the wastewater treatment process. The only effects on the activated sludge plant observed were: (1) nitrification was interrupted briefly as H2S diffusion commenced and (2) the species' diversity in the sludge decreased. PMID- 11762462 TI - Predicting odour impact using the Austrian odour dispersion model (AODM). AB - Using a dispersion model to calculate ambient odour concentrations, the separation distance between livestock buildings and residential areas is defined by the odour impact criteria using a combination of a pre-selected odour threshold and an exceeding probability. The dynamic Austrian Odour Dispersion Model (AODM), a Gaussian model, is used to calculate the direction-dependent separation distances for several combinations of these two values, which represent the protection level of various land use categories. The calculated direction-dependent separation distances are a function of the prevailing wind velocity and atmospheric stability conditions. At a site in the Austrian North alpine foreland, the direction-dependent separation distance (calculated on the basis of a two year time series of meteorological data) for pure residential areas (3% exceeding probability over the year for an odour threshold of 1 OU/m3) lies between 99 m (for northerly winds with a probability of less than 3%) and 362 m (for westerly winds with a probability of 34%). For west and east the main wind directions, odour sensation can be expected more often for higher wind velocities and a neutral or stable atmosphere around sunset. Northerly and southerly winds show the typical diurnal variation of a local valley wind system with predominantly northerly daytime up-valley and southerly night-time down valley winds. PMID- 11762463 TI - Development of a procedure to determine odour emissions from animal farming for regulatory purposes in Flanders. AB - The purpose of the project described in this paper was to develop a procedure to determine odour emissions at existing and new intensive animal farming houses. The procedure should be scientifically valid and preferably applicable on a large scale at reasonable costs. In this project odour emissions were measured during one year at the same farm. Measurements included 20 olfactometric sampling days and 50 sniffing measurements, all spread over one year. For each olfactometric sampling day, samples were taken in duplicate for the different pig categories. The olfactometric analysis resulted in the determination of odour emission factors for growing/fattening pigs, weaned piglets, dry sows and farrowing sows. The influence of external parameters (ventilation rate, inside temperature, outside temperature, pen dirtiness, number of pigs and their weight) was examined. Good correlation between the odour emission and an external parameter could only be found for the ventilation rate (r = 0.98) and outside temperature (r = 0.87). The sniffing measurements resulted in maximal odour perception distances and odour emissions calculated with short and long term dispersion models. No significant influence of the outside temperature (season) could be found here. The results of the olfactometric and sniffing measurements will be presented, including a combination of both techniques to determine the odour emission of an agricultural construction. PMID- 11762464 TI - Agricultural odours: 25 years of reducing complaints about barns and manure storages using the minimum distance separation formulae. AB - Ontario in Canada has a diverse livestock and poultry industry. Two million of Ontario's eleven million residents live in rural areas, but only 5% live on livestock and poultry farms, being outnumbered by their rural, non-livestock neighbours by 20:1. The increasing size, complexity, specialisation and concentration of livestock and poultry farms coupled with rural neighbours who have little or no family or business connection to them has resulted in an escalation in the number of odour complaints about barn and manure storage locations. Ontario-developed Minimum Distance Separation I and II formulae have helped site over 100,000 non-compatible uses, such as severed lots, away from livestock and poultry facilities, and similarly sited over 20,000 barns. However, they are under review because of the need to reflect the current and anticipated state of the livestock and poultry industry, the changing needs of the rural community, and to make it easier to apply for the growing number of municipal staff with little knowledge of the agricultural industry. PMID- 11762465 TI - Biotreatments of odours: control and performances of a biofilter and a bioscrubber. AB - Biotechnology has been applied to find systems to decrease the level of pollution. The main biological systems used in the deodorisation of waste gases are biofilters, biotrickling filters and bioscrubbers. These technologies work at normal operating conditions of temperature and pressure, and therefore they are relatively cheap with high efficiencies when the waste gas is characterised by high flow and low concentrations of odorous compounds. The aim of this work was to study the influence of different parameters (residence time of the gas phase, pollutant loads) of a biofilter and a bioscrubber on removal efficiencies. Ethanol was used as pollutant compound, because it is representative of both volatile organic compounds and odorous molecules. The performances of the two biological systems are presented and discussed. The use of pressure drop monitoring as a tool to control the operation of a biofilter and to obtain optimal conditions in a bioscrubber is proposed. PMID- 11762466 TI - Biofilters based on the action of fungi. AB - Traditional biofilters for waste gas treatment are mainly based on the degradation activity of bacteria. The application of fungi in biofilters has several advantages: fungi are more resistant to acidification and drying out, and the aerial mycelia of fungi form a larger surface area in the gas phase than bacterial biofilms, which may facilitate the uptake of hydrophobic volatile compounds. The research described here identifies important conditions for the operation of fungal-based biofilters. Biofilters with perlite packing were operated at different pHs and relative inlet gas humidities. Toluene was used as a model pollutant. It was shown that a low pH is a prerequisite for fungal growth in biofilters. Also, the fungal biofilters were more resistant to drying out and more active than the bacterial biofilters. Fungal biofilters eliminated 80-125 g toluene/m3 filterbed/h. Several measures that could limit the clogging of fungal biofilters with fungal biomass were investigated. The introduction of mites helped to control excessive fungal growth and pressure drop. The pressure drop of a perlite/fungi/mites filter of 1 m height, loaded with 200 m3 gas/m3 filter/h stabilised around 130 Pa. Biofilters based on the action of fungi are cost effective for the treatment of waste gases containing aromatic compounds, alkenes and other hydrophobic compounds. PMID- 11762467 TI - Technologies to address air quality issues impacting animal agriculture. AB - The continued productivity, profitability and sustainability of animal production agriculture in most parts of the world will be dependent upon implementation of effective technologies and management practices to mitigate perceived and documented environmental impacts resulting from confined animal operation emissions. North Carolina State University Animal and Poultry Waste Management Center (APWMC) program efforts to identify such technologies through support of research, development and demonstration projects involve collaborative efforts with approximately 20 other universities (nationally and internationally). Many of these projects are well beyond the laboratory developmental stage and some are yielding encouraging results. Performance data, to date, has shown that swine manure treatment systems including a covered in-ground anaerobic digester, a sequencing batch reactor, and an upflow biological aerated filter system significantly improved odor emission variables. PMID- 11762468 TI - Influence of different pig housing systems on odor emissions. AB - The odor emissions from two different housing systems were determined during three fattening periods from October 1999 to November 2000 by analyzing weekly samples by means of dynamic olfactometry. The objects of the investigations were a standard housing system with fully slatted floor and forced ventilation (FF) compared with a kennel housing system with natural shaft ventilation (KN) in parallel operation. Only little data but with a wide range of odor emission values are available from the literature and these are difficult to compare and interpret, because of missing standards in presenting the results and experimental conditions. Therefore minimum requirements for measuring odor emissions from livestock buildings have been derived. In the scope of the measurements during the first two fattening periods (October 1999 to June 2000), no differences in odor emissions could be determined with mean values related to the livestock units (1 LU = 500 kg life weight) of 85 (FF) /87 (KN) in period A and 60 (FF) / 61 (KN) (OU/s)LU(-1) in period B. The overall range of the results of all measurements in periods A and B was 4 to 355 (OU/s)LU(-1). In period C (August-November 2000), the system FF showed higher odor emissions with 193 (28 550) compared to system KN with 105 (25-218) (OU/s)LU(-1). The air flow rates and odor concentrations at the three different naturally ventilated exhaust shafts of system KN differed considerably from each other. Odor measurement techniques with a higher temporal resolution than olfactometry are necessary to give evidence for the main factors influencing the odor formation and release. PMID- 11762469 TI - Comparison of odour emissions from animal housing systems with low ammonia emission. AB - Nuisance from livestock facilities is an increasing problem in densely populated areas like The Netherlands. It is in the interest of both farmers and society that housing systems and management methods are developed to minimise the emission of odour. An odour research programme has been completed in The Netherlands to investigate odour emission from both conventional housing systems and systems designed for low ammonia emission. The aim of this paper is to compare within each animal category the odour emission of a number of swine housing systems and poultry housing systems. Emission measurements including 17 housing systems were carried out at 24 livestock facilities. Results showed that investigated systems with low ammonia emission for fattening pigs and sows were significantly (p<0.025) lower than conventional systems, being 50%, or more, lower. For laying hens and broilers, housing systems with low ammonia emission showed odour emissions that in most cases only differed slightly from conventional systems. Correlations between ammonia and odour concentration (within facilities) did not show a consistent pattern. It is concluded that methods for restriction of emitting (slurry) surface in pig husbandry may reduce both ammonia and odour emission. In poultry housings the effects of methods for ammonia reduction that involve drying of fresh manure or litter cannot be directly extrapolated to odour emision. PMID- 11762470 TI - Biofilters--the influence of different filter materials and different operating conditions on the reduction efficiency. AB - A series of biofilter materials were tested for performance efficiency in treating ventilation air from pig sheds. Two different phases were conducted. In phase A five different biofilter materials were tested with the aim of selecting the best material regarding the odor reduction and over all efficiency. In conclusion of phase A, biochips, a new filter material, was selected due to its high average odor reduction (81%) in combination with a very low flow resistance (less than 30 Pa for filter volume loads of 600 m3 h(-1) m(-3)). In phase B, biochips and coconut fiber peat were tested under different operating conditions. Biofilters number 3 and 4 each with down-flow air supply could realize a higher average odor reduction than biofilter 5 with up-flow air supply. All three filter materials had the same moisture, however the two biofilters with down-flow air supply showed a more homogenous moisture distribution but they also used approximately three times more water than biofilter 5. Like in phase A the specific odor cleaning efficiency was mainly influenced by the specific odor loading rate and showed only slight differences between the five biofilters differing in bulk layer height (0.5 m and 1.0 m) and air supply mode. All in all the investigation showed that the efficiency of biofilters can be optimized by using an new filter material and a appropiate operating mode. PMID- 11762471 TI - Biofilter media mixture ratio of wood chips and compost treating swine odors. AB - Biofilter media mixtures were compared in 18 pilot-scale biofilters treating pit gases from a swine facility. The compost and wood chips mixtures ranged from 100% wood chips to a 50-50 blend in 10% increments. The effect of three media moisture contents (low, medium, and high) on biofilter performance was also evaluated. Odor and hydrogen sulfide reduction did not change significantly for mixtures with greater than 20% compost. For efficient odor, hydrogen sulfide, and ammonia reduction media moisture must be greater than 40% wb. Media moisture content influenced odor, hydrogen sulfide, and ammonia reduction more than the ratio of compost and wood chips. The count of heterotrophic or sulfur-oxidizing bacteria did not change in a discernable pattern with respect to media mixture or moisture content. As the amount of compost increased in the media mixtures, the pressure drop also increased. Based on this experiment, the recommended mixing ratio of compost to wood chips for biofilters on swine facilities is minimum 30% compost and 70% wood chips by weight. PMID- 11762472 TI - Odour emission rates from manure treatment/storage systems. AB - The effects of agitation, liquid-only manure, depth and time on odour emission rates were investigated. Manure storage tanks were filled to incremental depths every two weeks. At each depth odour samples were collected twice. The second sample was collected seven days after the first. Odour concentration was measured with an olfactometer. Three different pig-manure treatments were investigated. In one treatment, slurry manure in a storage tank was agitated before and during odour sampling. In a second treatment, the settlable solids in manure were removed gravimetrically over 24 hours and liquid manure was pumped to a storage tank. In the third treatment (control), odour samples were collected from unseparated and undisturbed slurry manure. Overall, the odour emission rates in the agitated manure treatment ranged between 0.39 and 1.02 ou s(-1) m(-2), increased with depth and decreased with time, i.e. after seven days at each depth. In the liquid-only manure treatment, the emission rates ranged between 0.09 and 0.69 ou s(-1) m(-2), increased with depth but the effect of time was not evident. In the control treatment, the emission rates ranged between 0.20 and 0.66 ou s(-1) m(-2) and increased with depth on the first odour sampling day but decreased with depth on the second sampling day. PMID- 11762473 TI - Interlaboratory comparison of dynamic olfactometry in Central Europe 2000. AB - This paper presents the results of an interlaboratory comparison (ringtest) on olfactometry with 31 participants from four countries in Central Europe. The aim was to give evidence of the performance of dynamic olfactometry on the basis of the European Standard prEN 13725 (Draft) "Determination of odour concentration with dynamic olfactometry. The test included the analysis of three individual substances (n-butanol, hydrogen sulphide, tetrahydrothiophen) as well as a natural odour mixture (coffee flavour) to compare mean values and the standard deviations of results for the investigated samples. It was confirmed that laboratories working in compliance with the requirements of the new standard achieve a significantly better repeatability and reproducibility than those that are not compliant. PMID- 11762474 TI - A pilot-scale study on biofilters for controlling animal rendering process odours. AB - Heating of animal tissue during the process of rendering liberates a variety of odorous compounds. The performance of biofiltration in removing these odours was investigated using pilot-scale biofilters containing different media (sand, finely and coarsely crushed wood bark, and bark/soil mixture). Odour-removal performance of the biofilters was determined using olfactometry. Biofilter odour removal efficiencies of between 29.7% and 99.9% were measured at influent odour concentrations of between 143,100 and 890,000 odour units m(-3), and various air loading rates (0.074-0.592 m(-3) air m(-3) medium min(-1)). Biofilters with bark or bark/soil media and low air loading rates gave the best odour removal. The bark and sand biofilters generally maintained good odour reduction for about three years at an air loading rate of 0.148 m(-3) air m(-3) medium min(-1). Drainage from the biofilters contained significant concentrations of nitrogenous and organic compounds, suggesting that controlled leaching has the potential to remove accumulated substances in biofilter media from rendering gas emissions and increase the longevity of a biofilter system. High pressure drop across biofilter media can adversely affect the odour removal performance. Sand and fine bark, due to their small particle size, caused high pressure drops. Coarse bark showed negligible pressure drop at several examined air loading rates. Pressure drop also increased with moisture content, particularly in sand and fine bark biofilters. Overall pressure drop characteristics of the biofilters described in this paper were maintained without significant change over the three year operation. PMID- 11762475 TI - Biofiltration of dichlorobenzenes. AB - The use of air biofiltration for the degradation of dichlorobenzenes (1,2-DCB and 1,4-DCB) was studied at a refinery site. At this plant, 93 m3/h of contaminated groundwater, used in a cooling system and containing a maximum of 2 ppm of dichlorobenzenes, had to be treated. Stripping of the DCBs followed by biofiltration was selected as the most suitable technology to avoid volatilization in ambient air as expected with a wastewater aerobic treatment system. A stripper of 15 m height and 1.27 m diameter was designed as a first step treatment to volatilize DCBs with 3400 m3/h of air. Two f ull-scale biofilters of 70 m3 each were built and filled with 45 m3 of filtering media for the adsorption and biodegradation of the DCBs in the gas-phase. Filtering media was composed mainly of peat moss, with animal manure, wood chips and DCBs contaminated soil. Air to be treated was also contaminated with naphthalene. Laboratory tests showed an effective microbial activity in the contaminated soil and in the filtering media for DCBs degradation. Degradation of naphthalene induced slower degradation of DCBs. Full-scale operation was studied during four months. Water flow and DCBs content in the water entering the stripper were lower than expected with only 57 m3/h and a maximum concentration of only 240 ppb. Effective desorption was obtained in the stripper in the full-scale operation (more than 99% removal). Full-scale biofilters maintained a DCB concentration of less than 1 ppmv in the air outlet, but removal efficiency varied between 0 and 79% because of the low DCB inlet concentrations, load variations and sporadic naphthalene presence. PMID- 11762476 TI - A pilot study of a biotrickling filter for the treatment of odorous sewage air. AB - The nuisance impact of air pollutant emissions from wastewater treatment plants (WWTPs) is a major issue of concern to Singapore and to many developing cities worldwide. Existing chemical and physical treatment methods are efficient but costly, and may generate secondary pollutants. Biotreatment, on the other hand, is a proven control technology for effectively removing hydrogen sulphide (H2S), the principal odour component of sewage air. The biotechnology is cost-effective to remove low-concentrations of biodegradable compounds from a large flow of waste gases. A pilot-scale biotrickling filter, packed with pall rings, was set up at a WWTP in Singapore to investigate its effectiveness for treatment of odorous sewage air. A series of experiments were conducted to assess the performance of the biotrickling filter under various operating scenarios. Results indicated that even at 5 second gas retention time, the biotrickling filter could remove 95% of the inlet H2S. The behaviour of the biotrickling filter under various operating scenarios are presented and discussed in this paper. PMID- 11762477 TI - Removal of odor emitted from composting facilities using a porous ceramic biofilter. AB - A field experiment was conducted using a full-scale ceramic biofilter (approximately 150 m3/min) in order to determine the potential for biofiltration to remove malodorous gases from composting facilities. The main compounds found in malodorous gases were NH3 and H2S. These compounds were analyzed by a UV spectrophotometer and gas chromatograph. The microbial carrier was a porous ceramic consisting of diatomite and fly ash. About 12 m3 of ceramic media inoculated with waste activated sludge were filled in the biofilter. The experimental conditions were space velocity of 500 hr(-1), empty bed residence time of 7.2 s, and linear velocity of 0.2 m/s. About 90 L/d of water were sprayed for the operation. The NH3 concentration in inlet gases ranged from 8 to 90 ppmv. The concentration of H2S ranged from 3.2-5.5 ppmv. The acclimation of the biofilter was slow, but more than 95% of removal efficiency was achieved after one month of operation. No nutrients were supplied to the biofilter. The pressure drop in the biofilter varied from 20-40 mmAq during the operation. The energy consumption of this biofilter was about 200 kW/d. It was estimated that the deodorization using this ceramic biofilter was successfully carried out to remove the odor emitted from composting facilities. PMID- 11762478 TI - Odor control of an anaerobic lagoon with a biological cover: floating peat beds. AB - The use of a biological cover for in situ control of gaseous sulfide emission from an anaerobic pond was investigated by a laboratory-scale experiment. The biological cover, constituting by a peat bed floating on the wastewater, caused a reduction of the H2S emission rate by 84.6%. The addition of Fe3+ (with FeCl3) and plants (Juncus effusus L.) to the peat bed significantly improved the performance to reach a H2S removal of 95.5%. Despite the fluctuations in the sulfide concentration in the wastewater, the performance of the biological covers remained constant during the entire period of the study. The analysis of the different forms of sulfur accumulated in the peat beds allowed the understanding of the mechanisms involved in H2S removal. The high amount of sulfate demonstrated that the conditions were favorable to the biological oxidation of H2S. The addition of Fe3+ increased the formation of insoluble ferrous monosulfide (FeS) and pyrite (FeS2). The plants seemed to convert sulfate into elemental and organic sulfur. PMID- 11762479 TI - Laboratory investigation of supported permeable organic covers for the management of odour emissions from anaerobic piggery waste ponds. AB - Australian research has linked much of the odour arising from intensive livestock operations to pond treatment systems. A reduction in emissions from treatment ponds would therefore generally reduce odour emissions from intensive livestock operations. Published data indicates that the application of straw and other biological materials to effluent pond surfaces as a continuous cover reduces odour emissions. The effectiveness of these covers has not, however, been researched under controlled conditions. Using locally available materials, the efficacy of supported covers has been investigated using a series of laboratory anaerobic digesters treating typical piggery effluent. Research to date has focused on: identifying effective cover and cover support materials; quantifying odour reduction; identifying the impact use these covers may have on greenhouse gas emissions; devising practical and effective methods for constructing these covers. Results have confirmed that a variety of cover materials are effective in reducing pond odour emissions. Supporting the pond cover appears to extend the cover life expectancy. While greenhouse gas emissions appear to vary according to cover type, the overall significance of these emissions is not yet clear. The impact of permeable pond covers on overall pond performance requires additional research. PMID- 11762480 TI - Removal of hydrogen sulfide and methyl mercaptan by a packed tower with immobilized micro-organism beads. AB - To develop a more effective process for removing H2S and methyl mercaptan (MeSH), which are the important odorous components emitted from wastewater treatment facilities, a packed bed filled with immobilized micro-organism beads was studied. This study encompassed bacteria enrichment, evaluation of bacteria immobilization methods, determination of optimum operation parameters, such as environmental conditions for bacteria growth, removal rate of the packed bed etc. The experimental results are shown as follows: (1) the cultures able to metabolize H2S and MeSH can be enriched from activated sludge and the enrichment periods are 1-2 days and 7-10 days for H2S and MeSH, respectively; (2) the key environmental parameter influencing the cultures is pH value, the suitable ranges are 2-3 and 6-8 for H2S and MeSH, respectively; (3) the maximum removal rate for H2S and MeSH are 6500 g/m3 bed d and 4 g/m3 bed d, respectively; (4) the superficial M-M kinetics parameters are Vm: 11.2 g S/kg dry beads h and Ks: 95.8 mg/m3 for H2S, and Vm: 0.052 g S/kg dry beads and Ks: 2.1 mg/m3 for MeSH; (5) a two-stage biofilter operated in series under different pH values is recommended, which can remove the H2S and MeSH effectively. PMID- 11762481 TI - Use of electronic noses for detection of odour from animal production facilities: a review. AB - In the field of controlling livestock and poultry odours in the internal and external environment and in derived food products, one main obstacle is how to measure the odour in a suitable way. Olfactometry and a human panel have been used in most studies of farm odour until now. Alternatives like electronic noses are interesting considering disadvantages for olfactometry regarding cost and labour requirement. An electronic device can produce an almost instant response which is useful in many applications. Studies have shown detection of farm odour for some electronic noses and also response to odour concentrations. Other studies have shown very high odour threshold values compared to human noses. Electronic noses with a large number of sensors have been developed since a base was formed in the 1950s. The fast progress in data processing and sensor development in the latest years have made the electronic noses interesting for a large number of industrial applications in the food processing industry, as well as in other areas. Materials like manure produce a complex mixture of odorous compounds and the interaction between these creates a unique odour where no specific dominating and characterising compound seems to exist. Related to swine farms almost 200 different odorous compounds have been reported. The electronic noses can, depending on the sensitivity of its sensors, detect some compounds at lower levels than the human nose, while other compounds offensive to a human nose cannot be detected. Proper function of the electronic noses with sensitivity for the odorous gases in the application must be followed by satisfying properties regarding ageing, temperature stability, humidity and other environmental factors. PMID- 11762482 TI - Adverse effects of environmental odours: reviewing studies on annoyance responses and symptom reporting. AB - Air pollution control authorities dealing with odourous emissions from industrial, municipal and agricultural activities are often faced with many complaints from the public. In Germany, the Directive on Odour in ambient air provides a regulation system for the abatement of odour annoyance. Ambient air quality standards have been established based on investigations of the relationship between ambient odour load and community annoyance reaction. This paper describes a tool for the assessment of annoyance reactions, whereby degree of annoyance is correlated with ambient odour load. Systematic exposure response relations have been established for odour annoyance responses and symptom reporting for a variety of industrial sources. However, the precision of annoyance prediction from odour exposure measures rarely exceeds r2 = 0.17 in such studies. This is partly due to the fact that person-related factors, such as age, perceived health or stress coping styles, modify exposure response relations. The contribution of intensity and unpleasantness (hedonic tone) of ambient odours as modifying the annoyance reaction is currently investigated. PMID- 11762483 TI - Sensor arrays: an inspired idea or an objective measurement of environmental odours? AB - The measure of annoyance odours from sewage tratment, landfill and agricultural practise has become highly significant in the control and prevention of dorous emissions from existing facilities and its crucial for new planning applications. Current methods (such as GC-MS analysis, H2S and NH3 measurements) provide an accurate description of chemical compositions or act as surrogates for odour strength, but tell us very little about the perceived effect, whereas olfactometry gives the right human response but is very subjective and expensive. The use of non-specific sensor arrays may offer an objective and on-line instrument for assessing olfactive annoyance. Results have shown that sensor array systems can discriminate between different odour sources (wastewater, livestock and landfill). The response patterns from these sources can be significantly different and that the intensity of sensor responses is proportional to the concentration of the volatiles. The correlation of the sensors responses against odour strengths have also shown that reasonable fits can be obtained for a range of odour concentrations (100-800,000 ou/m3). However, the influence of environmental fluctuations (humidity and temperature) on sensor baselines still remains an obstacle, as well as the need for periodic calibration of the sensory system and the choice of a suitable gas for different environmental odours. PMID- 11762484 TI - Detection of the dynamics of odour emissions from pig farms using dynamic olfactometry and an electronic odour sensor. AB - The dynamics of odour emissions from a pig house was investigated by olfactometry and using an electronic odour sensor. In addition, several suggested influencing factors on the odour emission were measured to get insight into the reasons for the fluctuation of the odour emission. Odour emission tended to increase over the fattening period f rom August to November 2000 by a factor of two to three, although temperature and air-flow rate decreased according to the seasons. Feeding caused a significant temporary rise in animal activity, dust and odour concentration resulting in an increase of odour emission. The sensor signals of an electronic odour sensor increased simultaneously and showed a good relation to the odour concentration. There is a promising potential of electronic odour sensors to detect the dynamic and the level of odour concentrations. Further investigation will be done, to ensure a standardised measuring protocol and to obtain a calibration of electronic odour sensor signals direct to odour concentrations. PMID- 11762485 TI - Applicability of sniffing team observations: experience of field measurements. AB - Sniffing measurement campaigns are a commonly used technique in Flanders to estimate the impact of an odour emission source. The Department of Organic Chemistry at Ghent University has developed its own sniffing strategy throughout the last ten years. The method uses, in essence, the technique of plotting odour perception areas and calculation of total odour emission rates based on maximum odour perception distance. 566 sniffing measurements, executed from 1990 until 1999 around industrial and agricultural odour sources were collected in a database for statistical analysis. Short-term dispersion modelling was executed using four different models, two of them based on Bultynck-Malet dispersion parameters, and two based on Pasquill dispersion parameters. Results from this analysis demonstrate some causes of variance in calculated emissions and show the fitness of each model. From the results of the sniffing teams, which are expressed as sniffing units (SU) instead of odour units (OU, OUE) to underline the difference in methodological approach, the overall odorous emission can be calculated, using short-term atmospheric dispersion models. In a second step, long-term dispersion models can be used to calculate isopercentile contour plots. According to our experience the short-term atmospheric model is a source of "noise" in the method since calculated standard deviations on calculated emissions are larger than standard deviations in the observed maximum distance for odour perception. This will be illustrated by presenting results from the evaluation of composting plants and animal farm houses. PMID- 11762486 TI - Improvement of a wind-tunnel sampling system for odour and VOCs. AB - Wind-tunnel systems are widely used for collecting odour emission samples from surface area sources. Consequently, a portable wind-tunnel system was developed at the University of New South Wales that was easy to handle and suitable for sampling from liquid surfaces. Development work was undertaken to ensure even air flows above the emitting surface and to optimise air velocities to simulate real situations. However, recovery efficiencies for emissions have not previously been studied for wind-tunnel systems. A series of experiments was carried out for determining and improving the recovery rate of the wind-tunnel sampling system by using carbon monoxide as a tracer gas. It was observed by mass balance that carbon monoxide recovery rates were initially only 37% to 48% from a simulated surface area emission source. It was therefore apparent that further development work was required to improve recovery efficiencies. By analysing the aerodynamic character of air movement and CO transportation inside the wind-tunnel, it was determined that the apparent poor recoveries resulted from uneven mixing at the sample collection point. A number of modifications were made for the mixing chamber of the wind-tunnel system. A special sampling chamber extension and a sampling manifold with optimally distributed sampling orifices were developed for the wind-tunnel sampling system. The simulation experiments were repeated with the new sampling system. Over a series of experiments, the recovery efficiency of sampling was improved to 83-100% with an average of 90%, where the CO tracer gas was introduced at a single point and 92-102% with an average of 97%, where the CO tracer gas was introduced along a line transverse to the sweep air. The stability and accuracy of the new system were determined statistically and are reported. PMID- 11762487 TI - Development of a new dynamic chamber system for measuring harmful gas emissions from composting livestock waste. AB - A dynamic chamber system consisting of a chamber covering a composting mixture (3 m in diameter, 2.2 m in height, 13 m3), a ventilator for suction of air into the chamber, and equipment to measure the gas composition and indicate temperature, was developed for evaluation of harmful gas emissions from such livestock waste composting. Fresh air was introduced through the space between the floor and the lower edge of the chamber, and exhaust gas was removed through an outlet placed on top of the chamber. NH3, CH4 and N2O concentrations in exhaust air from the chamber were measured by Infrared Photoacoustic Detector (IPD, multi gas monitor type 1312, INNOVA, Copenhagen, Denmark) at 5 minutes intervals. The system was evaluated with standard gas of NH3, CH4 and N2O. High recoveries of 98.5% (NH3, SD 6.25), 96.6% (CH4, SD 4.03) and 99.5% ( N2O, SD 2.68) were obtained for each gas emission in the chamber over 17-20 min. The measured values of those gases obtained by the IPD method and conventional method at the time of a composting examination of swine waste were measured, and the differences were only a few percent of the total emissions. PMID- 11762488 TI - Comparison of different approaches used to regulate odours around the world. AB - A number of different countries, and states and local regulatory agencies within countries, have struggled with developing effective odour regulations or guidelines. The challenge is to develop regulations or guidelines that both avoid odour annoyance conditions and are not excessively conservative. This paper will present highlights of odour regulations or guidelines in Europe, Asia, Australia, New Zealand and North America. A comparison between the different approaches will be presented. With a number of countries reporting an increase in complaints due to odours, the field of odour assessment is rapidly evolving. Complaints due to odours from livestock facilities are also significantly increasing in many countries. A comparison of approaches used to regulate livestock operations is also included in the paper. The potential impact of European olfactometry standardisation efforts to existing assumptions about odour annoyance or nuisance levels is analysed. PMID- 11762489 TI - From odorant formation to odour nuisance: new definitions for discussing a complex process. AB - The process leading from odorant formation to individuals filing a complaint is complex, involving many steps and factors. A flow chart is proposed. The definitions that describe elements of this process, such as annoyance, nuisance, propensity of a population to experience nuisance, the "unpleasantness" of an odour, as used in odour literature, are often imprecise and confusing. A set of definitions is proposed to identify the issues involved and suggest a more precise use of terminology. A new definition for "annoyance potential" as an attribute of an odour is proposed. The concepts were developed for a study into the feasibility of developing a standardised method for measuring annoyance potential, funded by the programme "Improvement of the quality of Environmental Measurements", funded by the Ministry of Public Planning and the Environment in The Netherlands. The programme is expected to lead to a development programme, which will be outlined. PMID- 11762490 TI - Mechanics and aerodynamics of insect flight control. AB - Insects have evolved sophisticated fight control mechanisms permitting a remarkable range of manoeuvres. Here, I present a qualitative analysis of insect flight control from the perspective of flight mechanics, drawing upon both the neurophysiology and biomechanics literatures. The current literature does not permit a formal, quantitative analysis of flight control, because the aerodynamic force systems that biologists have measured have rarely been complete and the position of the centre of gravity has only been recorded in a few studies. Treating the two best-known insect orders (Diptera and Orthoptera) separately from other insects, I discuss the control mechanisms of different insects in detail. Recent experimental studies suggest that the helicopter model of flight control proposed for Drosophila spp. may be better thought of as a facultative strategy for flight control, rather than the fixed (albeit selected) constraint that it is usually interpreted to be. On the other hand, the so-called 'constant lift reaction' of locusts appears not to be a reflex for maintaining constant lift at varying angles of attack, as is usually assumed, but rather a mechanism to restore the insect to pitch equilibrium following a disturbance. Differences in the kinematic control mechanisms used by the various insect orders are related to differences in the arrangement of the wings, the construction of the flight motor and the unsteady mechanisms of lift production that are used. Since the evolution of insect flight control is likely to have paralleled the evolutionary refinement of these unsteady aerodynamic mechanisms, taxonomic differences in the kinematics of control could provide an assay of the relative importance of different unsteady mechanisms. Although the control kinematics vary widely between orders, the number of degrees of freedom that different insects can control will always be limited by the number of independent control inputs that they use. Control of the moments about all three axes (as used by most conventional aircraft) has only been proven for larger flies and dragonflies, but is likely to be widespread in insects given the number of independent control inputs available to them. Unlike in conventional aircraft, however, insects' control inputs are likely to be highly non-orthogonal, and this will tend to complicate the neural processing required to separate the various motions. PMID- 11762491 TI - Cephalopod chromatophores: neurobiology and natural history. AB - The chromatophores of cephalopods differ fundamentally from those of other animals: they are neuromuscular organs rather than cells and are not controlled hormonally. They constitute a unique motor system that operates upon the environment without applying any force to it. Each chromatophore organ comprises an elastic sacculus containing pigment, to which is attached a set of obliquely striated radial muscles, each with its nerves and glia. When excited the muscles contract, expanding the chromatophore; when they relax, energy stored in the elastic sacculus retracts it. The physiology and pharmacology of the chromatophore nerves and muscles of loliginid squids are discussed in detail. Attention is drawn to the multiple innervation of dorsal mantle chromatophores, of crucial importance in pattern generation. The size and density of the chromatophores varies according to habit and lifestyle. Differently coloured chromatophores are distributed precisely with respect to each other, and to reflecting structures beneath them. Some of the rules for establishing this exact arrangement have been elucidated by ontogenetic studies. The chromatophores are not innervated uniformly: specific nerve fibres innervate groups of chromatophores within the fixed, morphological array, producing 'physiological units' expressed as visible 'chromatomotor fields'. The chromatophores are controlled by a set of lobes in the brain organized hierarchically. At the highest level, the optic lobes, acting largely on visual information, select specific motor programmes (i.e. body patterns); at the lowest level, motoneurons in the chromatophore lobes execute the programmes, their activity or inactivity producing the patterning seen in the skin. In Octopus vulgaris there are over half a million neurons in the chromatophore lobes, and receptors for all the classical neurotransmitters are present, different transmitters being used to activate (or inhibit) the different colour classes of chromatophore motoneurons. A detailed understanding of the way in which the brain controls body patterning still eludes us: the entire system apparently operates without feedback, visual or proprioceptive. The gross appearance of a cephalopod is termed its body pattern. This comprises a number of components, made up of several units, which in turn contains many elements: the chromatophores themselves and also reflecting cells and skin muscles. Neural control of the chromatophores enables a cephalopod to change its appearance almost instantaneously, a key feature in some escape behaviours and during agonistic signalling. Equally important, it also enables them to generate the discrete patterns so essential for camouflage or for signalling. The primary function of the chromatophores is camouflage. They are used to match the brightness of the background and to produce components that help the animal achieve general resemblance to the substrate or break up the body's outline. Because the chromatophores are neurally controlled an individual can, at any moment, select and exhibit one particular body pattern out of many. Such rapid neural polymorphism ('polyphenism') may hinder search-image formation by predators. Another function of the chromatophores is communication. Intraspecific signalling is well documented in several inshore species, and interspecific signalling, using ancient, highly conserved patterns, is also widespread. Neurally controlled chromatophores lend themselves supremely well to communication, allowing rapid, finely graded and bilateral signalling. PMID- 11762492 TI - Fig-eating by vertebrate frugivores: a global review. AB - The consumption of figs (the fruit of Ficus spp.: Moraceae) by vertebrates is reviewed using data from the literature, unpublished accounts and new field data from Borneo and Hong Kong. Records of frugivory from over 75 countries are presented for 260 Ficus species (approximately 30% of described species). Explanations are presented for geographical and taxonomic gaps in the otherwise extensive literature. In addition to a small number of reptiles and fishes, 1274 bird and mammal species in 523 genera and 92 families are known to eat figs. In terms of the number of species and genera of fig-eaters and the number of fig species eaten we identify the avian families interacting most with Ficus to be Columbidae, Psittacidae, Pycnonotidae, Bucerotidae, Sturnidae and Lybiidae. Among mammals, the major fig-eating families are Pteropodidae, Cercopithecidae, Sciuridae, Phyllostomidae and Cebidae. We assess the role these and other frugivores play in Ficus seed dispersal and identify fig-specialists. In most, but not all, cases fig specialists provide effective seed dispersal services to the Ficus species on which they feed. The diversity of fig-eaters is explained with respect to fig design and nutrient content, phenology of fig ripening and the diversity of fig presentation. Whilst at a gross level there exists considerable overlap between birds, arboreal mammals and fruit bats with regard to the fig species they consume, closer analysis, based on evidence from across the tropics, suggests that discrete guilds of Ficus species differentially attract subsets of sympatric frugivore communities. This dispersal guild structure is determined by interspecific differences in fig design and presentation. Throughout our examination of the fig-frugivore interaction we consider phylogenetic factors and make comparisons between large-scale biogeographical regions. Our dataset supports previous claims that Ficus is the most important plant genus for tropical frugivores. We explore the concept of figs as keystone resources and suggest criteria for future investigations of their dietary importance. Finally, fully referenced lists of frugivores recorded at each Ficus species and of Ficus species in the diet of each frugivore are presented as online appendices. In situations where ecological information is incomplete or its retrieval is impractical, this valuable resource will assist conservationists in evaluating the role of figs or their frugivores in tropical forest sites. PMID- 11762493 TI - Undergraduate curriculum guidelines for endodontology. PMID- 11762494 TI - The use of ultrasound for cleaning the surface of stainless steel and nickel titanium endodontic instruments. AB - AIM: The aim of this study was to evaluate the efficacy of ultrasound in cleaning the surface of stainless steel and Ni-Ti endodontic instruments. METHODOLOGY: Twenty nickel-titanium instruments (10 Quantec files and 10 Nitiflex) and 20 stainless steel K-files (10 Maillefer-Dentsply and 10 Moyco Union Broach) were removed from their original packages and evaluated using a scanning electron microscope. Scores were given for the presence of residues on the surface of the instruments. The instruments were then cleaned in an ultrasonic bath containing only distilled water or detergent solution for 15 min, and re-evaluated, using scanning electron microscopy. RESULTS: Before cleaning, a greater amount of metallic debris was observed on the nickel-titanium Quantec instruments (P < 0.05), when compared to those made of stainless steel. Statistical analysis showed that the use of ultrasound was effective for cleaning the instruments, regardless of the irrigating solution or the instruments type (P < 0.05). CONCLUSIONS: The use of ultrasound proved to be an efficient method for the removal of metallic particles from the surface of stainless steel and Ni-Ti endodontic instruments. PMID- 11762495 TI - The effect of FIV infection on CD4+ and CD8+ counts in periradicular lesions. AB - AIM: The purpose of this study was to elucidate whether a decrease/increase in T cell populations is present in the development of periradicular disease in the immunocompromised feline model. METHODOLOGY: Eight cats were immunosuppressed with steroids prior to infection with feline immunodeficiency virus (FIV). Another eight cats, age and sex matched littermates, were monitored and tested at equivalent periods of time and served as uninoculated, seronegative controls. Periradicular lesions were induced using local bacterial inoculations into the pulp of the canine teeth and assessed after one- and four-week periods, corresponding to the acute and chronic stages of the periradicular disease. Block sections were obtained and specimens were prepared for H & E and immunohistochemical staining for CD4+ and CD8+ receptors. Cells were quantified using a computer imaging system and data analysed using generalized estimating equation (GEE) regression models. RESULTS: Significantly lower CD4+ counts and CD4+/ CD8+ ratios were observed at all time periods in the periradicular region of the FIV group (P = 0.0006). No significant difference in CD8+ counts was observed between the two groups. In both groups there was a significant difference in the CD4+ counts between one week and baseline, and 1 week and 4 weeks. There was no significant difference between baseline and 4 weeks for either group. CONCLUSION: FIV infection reflected decreased CD4+ counts at the periradicular level, however, inflammation and progression of the lesion, appeared to be comparable to the non-immunocompromised controls. PMID- 11762496 TI - The influence of specialty training and experience on decision making in endodontic diagnosis and treatment planning. AB - AIM: The purpose of this study was to compare the diagnostic and treatment planning decision making of cohorts of dental surgeons with different experiences and specialty backgrounds. METHODOLOGY: Periapical radiographs of 20 teeth in patients referred for an opinion regarding the provision of endodontic surgical retreatment were taken using a paralleling technique and a film holder. The radiographs were photographed and black and white photographic prints produced to provide an image 10.5 times larger than the original radiograph. Each image was related to a clinical scenario. Each participant was asked to assess whether a periradicular lesion, as manifested by a radiolucency, was present and what clinical management would be prescribed. Ten participants in each of seven groups took part in the study. These groups were chosen to represent those dentists who were most likely to be involved in decision making in similar cases. RESULTS: In 12 out of 20 cases interobserver agreement for radiographic analysis was 'excellent' (above 90%) or 'good' (between 70 and 90%). There was less agreement for treatment decisions than for radiographic analysis and the order of agreement for cases for diagnosis was not the same as for treatment. No case achieved 'excellent' percentage interobserver agreement. The average percentage interobserver agreement of the endodontists was significantly greater than the average percentage interobserver agreement for the other groups for both radiographic assessment and treatment decisions. CONCLUSIONS: Differences in specialty backgrounds amongst the participants in this study affected both endodontic diagnostic and treatment decisions. Endodontists showed the most consistent agreement amongst the specialty groups. PMID- 11762497 TI - A comparison of the quality of root canal treatment in two Danish subpopulations examined 1974-75 and 1997-98. AB - AIM: The aim of this study was to compare the quality of root canal treatment in two Danish subpopulations. METHODOLOGY: Group 1 (358 patients) was examined 1974 75 and group 2 (244 patients) 1997-98. All patients were more than 20 years old. All had undergone a full-mouth radiographic survey. In root-filled teeth the following parameters were assessed: the quality of the coronal restoration or crown, the lateral seal of the root filling, the length of the root filling, and the periapical status. Chi-squared tests were used for the evaluation of differences between the groups. RESULTS: In group 1 there were 975 endodontically treated teeth, in group 2 there were 753. In group 1 the majority of root-filled teeth were premolars, in group 2 the majority were molars (P < 0.001). The quality of coronal restorations (P = 0.35) and crowns (P = 0.68) did not differ significantly between the groups. In group 2 more teeth had adequately sealed root canals (P < 0.001) and adequate length of root filling (P < 0.001). More root-filled molar teeth had apical periodontitis (AP) than root-filled premolar and anterior teeth (P < 0.001). CONCLUSIONS: Whilst the technical quality of endodontic treatment had improved during the last 24 years, basic differences between the populations prevented assessment of the impact of this change on disease frequencies. The study indicates that great care should be taken when comparing different patient populations, in particular more emphasis should be placed on the selection and description of study groups. PMID- 11762498 TI - The quality of root fillings remaining in mandibular incisors after root-end cavity preparation. AB - AIM: The aim of this study was to determine the quality of root fillings remaining in mandibular incisors after root-end resection and root-end cavity preparation. METHODOLOGY: Roots of 40 mandibular incisors,12 mm in length, were divided into two groups and instrumented using a balanced force technique and obturated by vertically compacted warm gutta-percha. In one group sealer was used when back-filling the root canal with the Obtura System. The other group was also back-filled with the Obtura System but without sealer. The apical 4 mm of each root filling was removed by root-end resection and root-end cavity preparation. Fluid transport along the 7 mm of remaining root filling was measured. After the leakage test, horizontal sections were cut at a level 3 mm from the apical end of the remaining root filling. The cross sectional area of the canal and gutta percha was measured using an image analysis program. The quality of the remaining root fillings was also evaluated by calculating the percentage of gutta-percha filled canal area. RESULTS: In total, 27 (67%) out of the 40 roots demonstrated leakage. No significant difference was found between the two groups (P = 0.265). In the cross-sections the bucco-lingual canal diameter was up to 2.6 mm long (mean 1.6 mm). The average percentage of gutta-percha filled canal area was 85.6%. Warm gutta-percha could not obturate areas where debris remained after instrumentation. CONCLUSIONS: The quality of the root fillings in mandibular incisors was poor, probably because the unprepared recesses of oval canals were not clean. PMID- 11762499 TI - Root and canal morphology of Burmese maxillary molars. AB - AIM: To investigate the root and canal morphology of Burmese maxillary molars using a canal staining and tooth clearing technique. METHODOLOGY: Maxillary molars (239) were collected from indigenous Burmese patients and designated; first (90), second (77), third (72) molars. Following pulp tissue removal and canal system staining with Indian ink, the teeth were decalcified with 10% nitric acid, dehydrated and cleared with methyl salicylate. The following features were evaluated: (i) number of roots and morphology; (ii) number of canals per root: (iii) root canal configuration (Vertucci's classification); (iv) number of apical foramina per root; (v) number and location of lateral canals; and (vi) the presence of intercanal communications. RESULTS: All first and second molars had three separate roots, whilst third molars had one of five different root forms, of which three separate (25%) or fused (31%) roots were most prevalent. The majority of palatal (100%) and disto-buccal (96%) roots possessed one canal (type I). The prevalence of mesio-buccal roots with two canals decreased from first to third molars (68%, 49%, 39%, respectively); type II (two orifices, one apical foramen) and IV (two orifices, two apical foramina) configurations were the most common. Single/fused rooted third molars had a range of number and type of canals. Most roots in all molars had one apical foramen, those with four apical foramina were confined to third molars. Intercanal communications were most prevalent in mesio-buccal roots and two/three fused rooted third molars. Lateral canals were most prevalent in the apical third of the roots of all molars. CONCLUSIONS: The mesio-buccal roots of Burmese maxillary molars possessed a variety of canal system types. Over 50% of the first and second molars had a second mesio-buccal canal, of which over 20% had intercanal communications. The palatal and disto-buccal canals mainly had type I canals. Lateral canals were equally prevalent in all tooth types but were most common in the apical third. PMID- 11762500 TI - Curved molar root canal preparations using Hero 642 rotary nickel-titanium instruments. AB - AIM: The Bramante method was used to study how the natural curvature of root canals was modified when using the Hero 642 nickel-titanium rotary system. METHODOLOGY: Twenty-four canals were selected in freshly extracted human mandibular molars. Every root canal had an angle of curvature greater than 20 degrees. Roots were embedded in clear casting resin using a plaster mould. Cross sectional cuts were made in the apical, middle and coronal thirds of each root. A first group (control) of 12 curved root canals was prepared using stainless steel hand instruments and the step-back technique. A second group of 12 curved root canals was instrumented using the Hero sequence according to the manufacturer's instructions. For each sectioning level, the amount of dentine removed, the change of shape factor and the canal centre displacement were calculated with the aid of a digital image analysis system. The results were subjected to the Mann Whitney U-test. RESULTS: No significant difference occurred in the amount of dentine removed, change of shape factor or canal centre displacement in the coronal and middle thirds of the curved canals. In the apical third, transportation was significantly higher (P=0.0171) with stainless steel hand instruments than with the Hero system. CONCLUSIONS: The original canal shape was maintained better in the apical third of curved canals when using the Hero system in a crown-down technique when compared to a hand preparation technique with stainless steel instruments. PMID- 11762501 TI - Correlation between clinical success and apical dye penetration. AB - AIM: This study was undertaken to examine whether a correlation exists between apical dye penetration and the clinical performance of root fillings. METHODOLOGY: Apical dye penetration into 116 roots of human teeth that had been root-filled at least 6 months prior to extraction was tested in vitro using a vacuum technique and by measuring the length of dye penetration. Endodontic treatment was classified as clinically successful or unsuccessful and results for these groups were compared using analysis of variance and the Student's t-test. Positive and negative controls were used to test the experimental system. RESULTS: All controls performed as expected. Dye penetrated significantly further in unsuccessful cases although the raw data suggested little difference. Overall, dye penetrated 99.5% of the specimens, indicating that the presence of dye in the canal is a poor indicator of whether the technique or material will succeed. However, the extent of dye penetration may be related to the clinical outcome. CONCLUSIONS: Clinically placed root canal fillings do not provide an apical seal that prevents fluid penetration. The outcome of treatment cannot be predicted from the results of apical dye leakage studies. PMID- 11762502 TI - A case of unusual anatomy: a mandibular second premolar with four canals. AB - AIM: The aim of this case report is to describe conventional root canal treatment on a mandibular second premolar with four canals. SUMMARY: The pulp of a mandibular second premolar had become irreversibly inflamed, probably as a result of bacterial microleakage from a carious lesion. The general dental practitioner had initiated root canal treatment, but due to procedural difficulties referred the case. Conventional root canal treatment was then performed with magnification. Preparation was undertaken in a crown-down manner using balanced force hand instrumentation with flexible K-type files and files of Greater Taper. The root canals were obturated with vertically condensed gutta-percha technique. KEY LEARNING POINTS: Good illumination and magnification are vital during root canal treatment. Crown-down preparation using the balanced force technique with flexible files makes instrumentation easier and prevents many of the procedural errors that can occur with filing techniques. Greater Taper instruments made of nickel-titanium are sufficiently flexible to be used in complex curved canals and obviate the need for step-back flaring of the apical preparation. Vertical compaction of warm gutta-percha may simplify the obturation of complex root canal systems. When the technical difficulty of a procedure exceeds the expertise of the practitioner, specialist referral may be required. PMID- 11762503 TI - Root canal treatment in an unusual maxillary first molar: a case report. AB - AIM: The aim of this clinical article is to describe the unusual anatomy that was detected in a maxillary first molar during routine endodontic treatment. SUMMARY: Success in root canal treatment is achieved after thorough cleaning and shaping followed by the complete obturation of the root canal system. Such treatment may be performed in root canal systems that do not comply with the normal anatomical features described in standard textbooks. The present case describes root canal treatment in a maxillary first molar with two roots and a type IV canal configuration in the buccal root. KEY LEARNING POINTS Careful examination of radiographs and the internal anatomy of teeth is essential. Root canal treatment is likely to fail if the entire system is not debrided and filled. Anatomic variations can occur in any tooth. PMID- 11762504 TI - Cancer pain education: a structured clinical instruction module for hospice nurses. AB - The learning experience with the Cancer Pain Structured Clinical Instruction Module (SCIM), a highly structured skills training course for medical students, has been reported favorably. The purpose of this study was to present the Cancer Pain SCIM to registered nurses employed in a hospice setting. The goal of the study was to pilot test a structured cancer pain educational program for hospice nurses and to determine the perceived effectiveness of this course on the participants' cancer pain assessment and management skills. A multidisciplinary Cancer Pain SCIM was presented to 25 hospice nurses to improve their understanding of the management of cancer pain. The development group identified essential aspects of cancer pain management and then developed checklists defining specific station content. During the 2-hour Cancer Pain SCIM, nurses rotated through 8 stations in groups of 3, spending 15 minutes at each station. Eight instructors and 6 standardized patients, 5 of whom were survivors of cancer, participated in the course. All participants (students, instructors, and patients) evaluated the course, using a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree). Nurses provided self-assessments of their perceived competence on important aspects of cancer pain management both before and after the SCIM. The self-assessment items used a 5-point scale ranging from 1 (not competent) to 5 (very competent). Twenty-five hospice nurses, averaging 4.1 years (range 1-30 years) postgraduation, participated in the Cancer Pain SCIM. Overall, nurses agreed that they improved on each of the 8 teaching items (P < 0.001). The average (SD) pretest score of 2.8 (0.72) improved to 3.8 (0.58) on the post-test (P < 0.001). Nurses believed that their mastery of specific clinical skills, taught in all 8 stations, improved as a result of participation in the course. Nurses strongly agreed (mean +/- SD) that it was beneficial to use patients with cancer in the course (4.6 +/- 0.82). Faculty members enjoyed participating in the course (4.9 +/- 0.35) and indicated a willingness to participate in future courses (4.7 +/- 0.49). Significant perceived learning among hospice nurses took place in all aspects of the Cancer Pain SCIM. Participating nurses, instructors, and patients with cancer appreciated the SCIM format. Nurses and faculty considered the participation of actual patients with cancer highly beneficial. The SCIM format has great potential to improve the quality of cancer pain education. PMID- 11762505 TI - Life-extending therapies among patients with advanced cancer: patients' levels of pain and family caregivers' concerns about pain relief. AB - The purposes of this article are to explore the extent to which oncology unit patients with advanced cancer in Taiwan receive life-extending therapies and to examine the relationship of care goals (curative vs palliative) to levels of pain and family caregivers' concerns about pain reporting and analgesic administration. Forty pairs of patients with advanced cancer and their family caregivers (N = 80) were recruited from inpatient oncology units in Taiwan. Of these patients, 53% were receiving chemotherapy or radiotherapy for life extending or curative reasons as opposed to palliative goals. Patients with advanced cancer who were receiving life-extending therapies experienced lower levels of pain intensity than did those who were not receiving life-extending therapies. Moreover, Taiwanese family caregivers of patients with advanced cancer had concerns about reporting pain and administering analgesics regardless of whether the patient was receiving life-extending therapies. However, the family caregivers whose patients were receiving life-extending therapies were less concerned about using analgesics than were those caregivers whose patients were not receiving life-extending therapies. Finally, family caregivers' concerns about pain management as measured by the Barriers Questionnaire-Taiwan (BQT) form were related to family caregivers' reluctance to report their patients' pain. Implications of this study are discussed in terms of palliative care and pain educational programs. PMID- 11762506 TI - How relatives adjust after the death of a patient with cancer in hospice. AB - This study aims to discover (1) how relatives adjust to their new life situations following the death of a patient with cancer in hospice and (2) how those relatives have been supported by healthcare professionals both before and after the patient's death. The data were collected with a structured questionnaire administered to relatives of patients with cancer who died in a Finnish hospice in 1998 and 1999. The questionnaires were administered by the hospice staff to all family members who met the criteria specified (n = 589). The final sample comprised 258 family members, most of whom were the deceased patients' spouses. The Mann-Whitney U-test and the Kruskal-Wallis test were used to analyze the data. Instrument reliability was ascertained by the Cronbach alpha coefficient. The relatives had little difficulty accepting their new life situation and adjusting to their new role. The main factors affecting adjustment were being the patient's spouse and the age of both patient and relative. Relatives believed that they received a moderate amount of support from healthcare professionals, both before and after the patient's death. Most of the information they received concerned the patient's illness and treatment and daily condition. Communication was honest and based upon the relatives' needs. Emotional support before the patient's death consisted mainly of accepting the relative and listening to what relatives had to say. PMID- 11762507 TI - Cancer genetics fundamentals. AB - It is often said that cancer is genetic. What exactly does that mean? This article is our answer to that question at the turn of the millennium. We present models of carcinogenesis, review basic cancer genetics terminology, and explain some of the fundamental genetic changes common to all types of cancer. These are organized into 6 sections of (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) tissue invasion and metastases. Underlying all of these changes are the even more fundamental enabling factors of genetic instability on both the chromosomal and the gene level. Finally, we look toward the future in a field where the future is now! PMID- 11762508 TI - Being informed: undergoing radiation therapy. AB - This article aims to give insight into the experience of an intensive course of radiation therapy and relate the findings to the nurses working with individuals receiving radiation therapy. The purpose of this article is to describe and interpret the experiences of individuals undergoing radiation therapy in the cancer center of a large teaching hospital. The philosophic basis of this study was hermeneutic phenomenology and draws on the experiences described by 20 individuals undergoing radiation therapy through a series of unstructured interviews. The findings indicate that there are deficits in the care delivered in some radiation therapy departments. Information and preparation for radiation therapy are often inadequate or do not meet the needs of the individuals in this study. Participants continue to adopt a "sick" or "patient" role even though they attend treatments on an outpatient basis and are required to manage their own care, which results in a feeling of not being in control. Moreover, the coping styles of the participants vary and are not clearly identified and assisted by relevant health professionals. Care is not always well coordinated between the various health professionals, resulting in the patient receiving mixed or confusing messages about their treatments. PMID- 11762509 TI - Thai Buddhist patients with cancer undergoing radiation therapy: feelings, coping, and satisfaction with nurse-provided education and support. AB - Ninety male and 89 female Thai Buddhist patients with cancer undergoing radiation therapy at a Bangkok hospital outpatient radiation therapy clinic were subjected to a questionnaire study. The purpose of the study was to (i) describe feelings, coping, and satisfaction with nurse-provided education and support and (ii) identify possible gender differences. The results showed that the most common feelings of both genders at first knowledge about radiation therapy were "acceptance/calmness," and the women more often than the men felt "anxiety" and "fright/fear." The most common ways of coping with radiation therapy for both genders were "rest," "talk with family/friends," "visit doctor," and "meditate," and in this regard there were no significant gender differences. The men expressed their highest satisfaction with "nurse has knowledge about disease/treatment" and "nurse listens to patient's problem," whereas the women expressed their highest satisfaction with "patient dares to ask questions" and "nurse likes to explain information." The satisfaction with different aspects of nurse-provided education and support was commonly higher among the men. When oncology nurses are to provide education to radiation therapy patients, it is essential that they are aware of their patients' characteristics, such as the ones identified here, that are related to cultural values and religious beliefs as well as to gender. PMID- 11762510 TI - Relilgious beliefs and practices of Taiwanese parents of pediatric patients with cancer. AB - The aim of this study was to increase understanding of religious beliefs and practices among Taiwanese parents of pediatric patients. Parents of 63 pediatric patients with cancer were interviewed to explore their related religious beliefs and practices, ie, worship at temple, drawing Chien, and divinations. Rituals were used to diminish the harmful effects of the child's disease, such as temple ceremonies, changing the child's name, and taking "Fu" water. Such practices were generally undertaken with a lack of medical guidance from oncologists largely because of poor interactions between parents and oncologists. The findings suggest that discovering a caregiver's worldview and cultural values is important to establish holistic nursing practices. Because immigrants increasingly move around the world, Taiwanese parents become a culturally diverse clientele for healthcare professionals who have to be aware of the existing cultural differences in healthcare values, patterns, and practices, particularly between Western and Eastern cultures. PMID- 11762511 TI - Determining the needs of chinese parents during the hospitalization of Their child diagnosed with cancer: an exploratory study. AB - In Hong Kong, as in other modern societies, cancer is the second cause of death among children. Studies show that childhood cancer affects all family members who frequently experience emotional and social problems resulting from managing the stress created by the disease and side effects of treatment. This subsequently results in parents experiencing a range of different needs. There is little evidence available of the needs of Chinese parents during the hospitalization of their child. An exploratory study was undertaken using in-depth semistructured interviews with 5 parents recruited from the pediatric oncology ward of a regional hospital in Hong Kong. The parents were interviewed twice during the active treatment phase to explore their changing needs during this initial period of hospitalization. All interviews were tape-recorded, transcribed, and translated into English before content analysis. The analysis of the parents' data identified 6 main categories common to both interviews: (i) the need for recognition of their reaction, (ii) the need for recognition of their fear of hospitalization, (iii) the need for support, (iv) the need for information, (v) the need for personal time, and (vi) finally the need for help in parenting skills were identified. The implications of these findings for nursing practice are presented. PMID- 11762512 TI - The relationship between disease features and quality of life in patients with cancer--I. AB - The high incidence and the severe symptoms of cancer have a considerable effect on quality of life in patients. The relationship between quality of life in patients with cancer and treatment, early diagnosis, disease acceptance, pain, psychological distress, loss of organ, duration of disease, and caregivers was investigated. This study included 508 patients with cancer treated in either inpatient or outpatient clinics of 5 oncology centers in Ankara, Turkey, between August 1 998 and January 2000. Patients were selected by interviews. Data were collected by a questionnaire to determine disease features and to evaluate patients' quality of life. We found that several disease features, including treatment, early diagnosis, disease acceptance, pain, psychological distress, and caregivers, had an effect on patients' quality of life (P < 0.05), whereas loss of organ and duration of disease did not. The results of this study underline the significant effect of psychosocial care programs on quality of life. In the future, assessments of quality of life can help healthcare personnel to prepare psychosocial care programs. PMID- 11762513 TI - Meta-analysis of the effect of the use of computer-based systems on the metabolic control of patients with diabetes mellitus. AB - The purpose of this study was to evaluate, through a meta-analysis study, whether the use of computer-based systems reported in the literature improves the metabolic control of diabetic patients. On the retrieved papers, a set of meta analysis studies were performed: first the difference of HbA1c between cases and controls at follow-up was evaluated (sign test); then the difference between cases and controls in the total variation of HbA1c from the beginning to the end of the trial was considered (method of effect sizes). The latter methodology was reapplied also on three more homogeneous article subgroups. The sign test was performed on 16 papers: in two of them, the HbA1c level was higher in the intervention group than in the control group at follow-up: it is unlikely that this is a random occurrence (p < 0.01). The method of effect sizes was first applied to 13 papers, as in the others some needed data were missing: the results obtained showed a statistically significant amelioration of metabolic control in the intervention group in comparison to the control group (p < 0.01). A progressive reinforcement of this outcome was obtained on the trial subgroups. Our study supports the hypothesis that the use of computer-based systems can be an effective means of improving metabolic control. The differential benefit obtained in the amelioration of HbA1c does not justify, by itself, the applicability of such systems into clinical practice; additional investigations should be carried out to evaluate the enhancement of other clinical and organizational indicators. PMID- 11762514 TI - Comparison of glucose concentration in interstitial fluid, and capillary and venous blood during rapid changes in blood glucose levels. AB - The relationship between glucose concentrations in interstitial fluid (ISF) and blood has generated great interest due to its importance in minimally invasive and noninvasive techniques for measuring blood glucose. The relationship between glucose levels in dermal ISF, and capillary and venous blood was studied with the dermal ISF samples obtained using the suction blister technique. The study was conducted with intensely managed diabetics whose blood glucose levels were manipulated so as to induce rapid changes in blood glucose levels. Glucose levels in the three compartments exhibited high correlations both when individual subjects were considered separately and when data from all subjects were combined. No significant time lag during glucose excursions was observed among the ISF, and capillary and venous glucose levels. PMID- 11762515 TI - Physiological influences on off-finger glucose testing. AB - Products for monitoring blood glucose that allow extraction from sites other than the finger have recently been introduced. The FreeStyle Blood Glucose Monitor requires only 0.3 microL of blood, and allows extraction from the hand, arm, and leg, as well as the traditional finger site. Differences in circulatory physiology of the off-finger test sites lead to differences in the measured blood glucose concentration. The first study involved 160 clinic visits by 120 unique subjects with type 1 or type 2 diabetes. FreeStyle measurements were compared to YSI Model 2300 Stat Plus Glucose Analyzer plasma measurements using venous blood, capillary blood from the finger, and capillary blood from the arm. In a second study, the time course of glucose variation was tested by simultaneous measurements on the arm and finger taken every 15 min for 6 h. Thirteen subjects with type 1 diabetes were studied in two 6-h sessions. When FreeStyle was compared to YSI using venous samples and finger samples, the regression statistics were very similar. But when FreeStyle with arm samples was compared to YSI with finger samples, the regression equation was similar, but the scatter in the data was statistically significantly greater at the 95% confidence interval. By studying the time course of glucose changes, the difference between finger and arm measurements was attributed to a time lag in the glucose response on the arm with respect to glucose response on the finger. The lag was observed when the glucose concentration was increasing or decreasing, and the lag time varied from subject-to-subject in the range of 5-20 min. Using the Clarke Error Grid Analysis, the difference between arm and finger glucose measurements was not clinically significant. However, when the glucose concentration is decreasing rapidly into a state of hypoglycemia, the lag in measurements on the arm could delay detection of hypoglycemia. When specifically testing for hypoglycemia, the finger may be the preferable test site. PMID- 11762516 TI - Information technology and home glucose clamping. AB - Persons with diabetes are responsible for the day-to-day control of their glycemia. To assist patients in discharging this responsibility and help them achieve and sustain improvements in self-blood glucose control, we developed information technology capable of executing algorithms for "clamping glucose" at home. Algorithms for laboratory glucose clamping were translated and adapted for use by patients. The procedures were supported by a central computer and registry. Interaction with the algorithms from home required the patient to handle only a touch-tone telephone, which accessed voice response hardware in the central computer. Patients reported self-measured blood glucose levels or hypoglycemia symptoms together with dietary changes, planned exercise, stress, illness or other lifestyle events. In response, they received self-management instructions and dosing decision support. Metabolic end points were measured. System beta testing in active patients was for 1 year. Patients (n = 142) used the algorithms for their daily self-management, accumulating 1,651 patient-months of follow-up. Almost 100,000 telephone calls were received. Patients benefited. Prevalence of diabetes related crises (hyperglycemia > 400 mg/dL, hypoglycemia < 50 mg/dL or symptoms without measurement) fell approximately twofold (p < 0.05) and glycated hemoglobin levels fell 1.3% (p < 0.001), while body weight was stable. Providers benefited from the timely receipt of standardized reports to monitor the progress of their patients. Earlier intervention was possible. Information technology facilitated home glucose clamping whereby patients with diabetes received timely assistance, advice and decision support for crucial self control of blood glucose levels. This empowered patients to achieve independence and improve diabetes self-management. PMID- 11762517 TI - Factors affecting the deposition of aerosolized insulin. AB - The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their efficiency (measured, for example, in terms of the amount of insulin absorbed in the blood compared to the total amount loaded into an inhalation device). A primary factor that could cause inefficiency of insulin absorption is deposition in the nonalveolated airways with subsequent removal from the lung via mucociliary clearance. Thus, a better understanding of the spatial distribution of insulin particle deposition in the lung can give guidance to the optimization of inhalation therapy. A mathematical model was used to study factors affecting the disposition of aerosolized insulin. The model calculates the trajectories of inhaled particles in the lung and has been validated by data from human subject experiments. Computer simulations were performed describing a wide range of patient breathing maneuvers. The results indicate significant variations in particle deposition patterns within lungs for different tidal volumes, inspiratory flow rates, and breath hold times. These findings indicate that particle sizes and ventilatory parameters are significant factors determining locations of particle deposition within human lungs, and thus the absorption of insulin into the blood stream via alveloated airways. Mathematical modeling is a valuable technique to complement clinical studies in the targeted delivery of inhaled insulin. PMID- 11762519 TI - Home fructosamine testing: will it improve diabetic control? PMID- 11762518 TI - Dual-test monitoring of hyperglycemia using daily glucose and weekly fructosamine values. AB - The purpose of this study was to assess the impact of using a dual-test blood glucose/fructosamine home monitoring system to assist individuals identified as having the potential for poor glycemic control to achieve values closer to normal. Forty-eight subjects found to have a fasting blood glucose value of > or = 126 mg/dL, casual blood glucose value of > or = 140 mg/dL, and/or blood fructosamine value of > or = 310 micromol/L, agreed to perform daily self testing for 90 days and were provided a dual-test blood glucose/fructosamine home monitoring system and testing supplies at no charge to them. Medication changes/compliance along with dietary and exercise habits were compared to testing results by the principle investigator at approximate 30-day intervals. The desired goal of this project was to achieve and/or maintain a fasting blood glucose value of < or = 110 mg/dL, a casual blood glucose value of < or = 140 mg/dL and a blood fructosamine value of < or = 310 micromol/L by encouraging each individual to realize the effect of dietary intake and exercise habits, and understand the importance of medication compliance, if appropriate, in achieving better overall glycemic control. Four subjects withdrew from the study prior to completion, 11 of the remaining 44 completed 60 days of testing and 33 of 44 completed 90 days of testing. Regular monitoring and counseling achieved an average reduction in blood glucose of 27.5% and a 16.6% reduction in average blood fructosamine when compared to original screening results of these 44 individuals. This study indicates that the addition of weekly fructosamine values to daily blood glucose values provides both the patient and clinician valuable information to evaluate the impact of dietary, exercise, and medication therapy changes on glycemic control by bridging the existing gap between daily blood glucose values and quarterly HbA1c confirmation of intervention results. PMID- 11762520 TI - Benchmark data from the literature for evaluation of new glucose sensing technologies. AB - New glucose sensors based on various technologies are being developed to provide information for improved therapy in diabetes. There is a need to establish rational performance standards for these sensors. Frequently sampled, direct blood glucose recordings representative of blood glucose excursions in diabetes are the "gold standard." An extensive literature search revealed a limited number of diabetic and nondiabetic blood glucose recordings suitable for this purpose. Certain blood glucose recordings reflect the diversity of glycemic dynamics and provide sufficient challenge for evaluation of sensor systems. These recordings were converted into an accessible electronic format. An example is given of the use of these benchmark data to estimate aliasing error, or the error due to insufficient sampling frequency, based on a hypothetical sensor system having some properties of conventional "fingerstick" systems. Discrete sampling systems accumulate substantial aliasing error as the sampling period increases. PMID- 11762521 TI - Graphical human insulin time-activity profiles using standardized definitions. AB - The purpose of this study was to (1) develop consistent definitions to report time-activity profiles of insulin formulations, (2) determine human insulin time activity profiles based on all available pharmacokinetic studies of biosynthetic human insulin rDNA(E. coli) (Humulin), and (3) create graphs that accurately and usefully represent human insulin time-activity profiles (TAPs). Standard definitions of onset, peak, duration, and time of 50% maximal activity were developed for human insulin. Results from all pharmacokinetic and pharmacodynamic studies available on human insulin from searches of both published literature and unpublished work were analyzed by these standard methods. Data obtained using these definitions were used to construct diagrams of the time-activity relationships for each formulation. Sixty-three insulin tests utilizing a variety of methodologies and data analysis techniques were located. Time-activity curves generated by application of standardized definitions varied depending on methodology, and on whether glucose, insulin and/or glucose infusion rates were used as the measure of insulin activity. A method of standard analysis is required for evaluating insulin pharmacokinetic studies due to the wide variation in design of these studies. Graphic representation of ranges obtained by standard analysis of onset, peak, duration, and 50% maximal activity increase the information transmitted when compared to currently used tables of time-activity data. The time of 50% maximal activity during increasing and decreasing phases may be a better marker of clinically significant activity than the classically defined parameters of onset and duration. PMID- 11762522 TI - Bioartificial pancreas: materials, devices, function, and limitations. AB - The term "bioartificial endocrine pancreas" (BEP) was introduced by Anthony Sun in 1980. It was in 1968, however, that Thomas Chang proposed the use of microencapsulated islets as artificial beta-cells. By applying a semipermeable membrane on the top of microcapsules, a system can be produced that is impermeable to viable islet cells and large effector molecules of the immune system, thus providing a protection for transplanted islets against rejection. Since then, the term BEP has not often appeared in papers. Instead, the term "bioartificial pancreas" (BAP) has gained widespread use. In a broader sense, BAP would include an application of suitable endocrine cells and protective polymeric vehicles, but not necessarily providing a filtration barrier of precisely defined properties (e.g., cells injected into a gel of hyaluronate). PMID- 11762524 TI - Noninvasive diabetes technology development: report from the Institute for International Research Symposium. PMID- 11762523 TI - Diabetes vaccines: a future to be realized. AB - Immune-mediated (type 1) diabetes mellitus (IMD) is an autoimmune disease resulting from the chronic destruction of pancreatic islet cells by autoreactive T lymphocytes. Although there has been much advancement in diabetes management, targeting the precise etiology of the disease process has remained elusive. Recent progress in the understanding of the immunopathogenesis of IMD, however, has led to new intervention strategies, especially antigen-based therapies given as altered peptide ligands (APLs) or as vaccines. Instead of using immunosuppressive agents to suppress an already dysfunctional immune system, antigen specific vaccines or even non-antigen specific immunostimulants present a unique opportunity to boost regulatory function and thereby regain tolerance to self. We discuss here the pathogenesis of IMD as it relates to therapeutic possibilities, review various intervention strategies that have been successful in rodent models, and then present recent progress in human trials of diabetes intervention and prevention through vaccine prototypes. PMID- 11762525 TI - Hypoglycemia and the brain. PMID- 11762526 TI - Simulating glycosylated hemoglobin (HbA1c) levels in diabetes using an interactive educational virtual diabetes patient simulator. AB - In 1996, an interactive educational diabetes simulator called AIDA was released without charge on the Internet as a noncommercial contribution to continuing diabetes education. Over the past 5 years, over 100,000 people have visited the AIDA Web pages at http://www.2aida.org and over 25,000 copies of the program have been downloaded free-of-charge. Previous Diabetes Information Technology & WebWatch columns have described various user feedback comments about the AIDA software. This current column overviews the method applied for modelling glycosylated hemoglobin (HbA1c) levels within an updated version of the AIDA program (v4.3). The result seems to be a useful and novel addition to the diabetes simulations, providing a parameter with which most users will be familiar, and able to relate. It is expected that the HbA1c indicator may prove useful in enhancing the educational value of the diabetes simulations. PMID- 11762527 TI - Increased lipid peroxidation in pregnant women after iron and vitamin C supplementation. AB - Iron overload could promote the generation of free radicals and result in deleterious cellular damages. A physiological increase of oxidative stress has been observed in pregnancy. A routine iron supplement, especially a combined iron and vitamin C supplementation, without biological justifications (low hemoglobin [Hb] and iron stores) could therefore aggravate this oxidative risk. We investigated the effect of a daily combined iron supplementation (100 mg/d as fumarate) and vitamin C (500 mg/d as ascorbate) for the third trimester of pregnancy on lipid peroxidation (plasma TBARS), antioxidant micronutriments (Zn, Se, retinol, vitamin E, (beta-carotene) and antioxidant metalloenzymes (RBC Cu-Zn SOD and Se-GPX). The iron-supplemented group (n = 27) was compared to a control group (n = 27), age and number of pregnancies matched. At delivery, all the women exhibited normal Hb and ferritin values. In the supplemented group, plasma iron level was higher than in the control group (26.90 +/- 5.52 mmol/L) and TBARs plasma levels were significantly enhanced (p < 0.05) (3.62 +/- 0.36 vs 3.01 +/- 0.37 mmol/L). No significant changes were observed in plasma trace elements and red blood cell antioxidant metalloenzymes. Furthermore, the alpha-tocopherol plasma level was lowered in the iron-supplemented groups, suggesting an increased utilization of vitamin E. These data show that pharmalogical doses of iron, associated with high vitamin C intakes, can result in uncontrolled lipid peroxidation. This is predictive of adverse effects for the mother and the fetus. This study illustrates the potential harmful effects of iron supplementation when prescribed only on the assumption of anemia and not on the bases of biological criteria. PMID- 11762528 TI - Reduction of vanadium(V) with ascorbic acid and isolation of the generated oxovanadium(IV) species. AB - The interaction of sodium metavanadate and VOCl3 with ascorbic acid, one of the possible natural reducing agents of vanadium(V) to oxovanadium(IV), has been investigated. Three new VO2+ complexes could be isolated as microcrystalline powders. One of them, of composition K1.5Na0.5[VO(HAsc)(OH)3], contains ascorbic acid as a monodentate ligand. In the other two, K[VO(Diketo)(OH)] x H2O and Na3[VO(Diketo)2(OH)], the enolized form of 2,3-diketogulonic acid (one of the oxidation products of ascorbic acid), acts as a bidentate ligand. The complexes were characterized by means of electronic (absorption and reflectance) and infrared spectroscopy and magnetic susceptibility measurements. Their thermal behavior was investigated by thermogravimetric and differential thermal analyses. The interest of the investigated system in relation to vanadium detoxification is also discussed. PMID- 11762529 TI - Relationships among element contents in the intimal, middle, and external tunicae of the thoracic aorta. AB - To examine an accumulation of elements within the arteries with aging, the authors investigated the element contents in the intimal, middle, and external tunicae of the thoracic aorta. The subjects consisted of six men and four women, ranging in age from 57 to 99 yr. The wall of the thoracic aorta was separated into the intimal, middle, and external tunicae by scrubbing the wall of the thoracic aorta with an edge of slide glass and the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were significant relationships among calcium, phosphorus, magnesium, sulfur, and sodium in both the intimal and middle tunicae of the aorta, but not in the external tunica. These results revealed that no significant differences were found in element compositions of deposits between the intimal and middle tunicae. PMID- 11762530 TI - Classification and prognostic value of serum copper/zinc ratio in Hodgkin's disease. AB - The serum copper and zinc levels were determined by atomic absorption spectrometry in 135 Hodgkin's disease (HD) patients and in 100 healthy controls. These values were used to explore the application value of the serum copper/zinc ratio in the histologic classification and prognosis in this illness. The resuls show that serum copper and the copper/zinc ratio were higher and the serum zinc level was lower in the HD patients when compared to the healthy individuals (p < 0.01, 0.001, and 0.01, respectively). The serum copper and copper/zinc ratio were significantly higher in the lymphocyte-depleted type of HD than in the patients with the mixed-cellular type of HD. These values were also higher and the serum zinc was lower in the patients with mixed-cellular HD when compared to the nodular-sclerosis and the lymphocyte-predominant types of the disease (p < 0.01 and 0.001, respectively). It was also shown that as the disease progresses, the serum copper level and copper/zinc ratio rises with the concomitant decrease of the corresponding serum zinc level. These trends are reversed in cases where the disease is in remission. Both the serum copper level and the copper/zinc ratio were strongly correlated to histopathological changes, clinical stage, and prognosis of Hodgkin's disease. PMID- 11762531 TI - Effects of lithium on thrombopoiesis in patients with low platelet cell counts following chemotherapy or radiotherapy. AB - Therapy for neoplasma is limited by hematological side effects of tumor destructive therapy and, in part, makes expensive supportive care necessary to overcome and treat leukopenia and thrombocytopenia and their consequences. Thrombocytopenia is a major clinical problem caused by chemotherapy and radiotherapy. An effective and very cost-effective option for treating moderate neutropenia is the administration of lithium carbonate. Lithium induces the release of colony-stimulating factors (CSF) and therefore stimulates proliferation of neutrophil granulocytes. Other cytokines, such as interleukin-1 (IL-1), IL-6, and tumor-necrosis factor-alpha (TNF-alpha), are also stimulated. Apart from granulocyte-macrophage-CSF (GM-CSF), there have as yet been no reports of lithium salts inducing early activating factors for the megakaryocytic lineage, such as IL-3, IL-11, stem cell factor and flt-3 ligand, or maturation factors, such as thrombopoietin (TPO). A statistically significant increase in the mean number of platelets for patients with cell counts below 150,000/microL on the commencement of treatment with lithium carbonate could be observed. Patient tolerability of lithium carbonate therapy is very good. Patients with persistent leukopenia and thrombocytopenia following chemotherapy or radiotherapy can be treated with this trace element very cost-effectively. Unfortunately this treatment has not gained acceptance in clinical oncology in the face of extremely cost-intensive treatment with recombinant GM-CSF, IL-11 or, potentially, thrombopoietin. PMID- 11762532 TI - Dietary titanium and infant growth. AB - Dietary titanium as TiO2+ improved animal growth during infancy while inhibiting the metabolism of intestinal bacteria. TiO2+ was also found capable of inhibiting human cytomegalovirus in tissue culture. These and other findings indicate TiO2+ improves infant growth by acting as an antibacterial and antiviral agent. The behavior of TiO2+ stands in contrast to that of TiO2, which is inert. PMID- 11762533 TI - Effect of dietary zinc intake on N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats. AB - Numerous studies have shown that zinc nutrition influences the growth of several types of tumor. However, the influence of zinc nutrition on mammary tumorigenesis is not known. To study the effects of dietary zinc intake on N-methyl-N nitrosourea (MNU)-induced mammary tumorigenesis, female Sprague-Dawley rats were fed an egg-white-based diet providing 3 (Z3), 12 (Z12), or 31 (Z31) mg zinc/kg diet ad libitum. In addition, two pair-fed controls, PFZ12 and PFZ31, were also included. Fourteen weeks after MNU injection, cumulative tumor incidence and total number of tumors were lower in Z3 rats than in Z12 and Z31 rats. Cumulative tumor incidence and total number of tumors were lower in Z3 rats than in PFZ12 rats, but were the same as in PFZ31 rats. Cumulative tumor incidence and total number of tumors were also lower in pair-fed controls than in their corresponding ad libitum controls, but were the same between the ad libitum controls. Overall, the results showed that the effect of marginal zinc deficiency on MNU-induced mammary tumorigenesis in rats was primarily the result of a reduced feed intake associated with marginal zinc deficiency rather than zinc per se. PMID- 11762534 TI - Determination of plasma trace elements in tumor-bearing animals by proton-induced X-ray emission spectroscopy. AB - Although altered levels of circulating essential trace elements are known to accompany malignant disease, the lack of sensitivity of conventional detection methods has generally limited their study to clinical conditions involving extensive disease (i.e., significant tumor burden). As such, the application of altered trace element levels as potential prognostic guides or as response indicators subsequent to treatment has been of limited use. During this study, proton-induced X-ray emission spectroscopy was evaluated as a tool to determine trace element imbalances in a murine tumor model. Using plasma from C57B1/6 mice bearing the syngeneic Lewis lung carcinoma (LLCa), levels of Fe, Cu, and Zn, as well as changes in the Cu /Zn ratio, were measured in animals carrying an increasing primary tumor burden. The plasma levels of Fe, Cu, and Zn were found to decrease significantly 7 d following implants of LLCa cells with no significant change observed in the Cu/Zn ratio. By d 21, however, an increase in the Cu/Zn ratio was found to accompany increased growth of the LLCa tumor; the plasma levels of Cu had returned to normal levels, whereas both the Fe and Zn plasma levels remained lowered. Collectively, the results suggest that although a net change in individual plasma trace element concentrations might not be accurately associated with tumor growth, a clear relationship was established between the Cu/Zn ratio and tumor size. PMID- 11762536 TI - Ultrasound into the future. PMID- 11762535 TI - Micronucleus frequencies in workers exposed to lead, zinc, and cadmium. AB - Micronuclei (MN) in blood lymphocytes were determined in 31 male workers occupationally exposed to lead (Pb), zinc (Zn), and cadmium (Cd) and 20 control workers matched for age and smoking habits. Exposed workers have higher MN mean values than control workers (p < 0.01). In exposed workers, blood Pb concentrations were also significantly higher than in control workers (p < 0.001), but the mean concentrations of Zn and Cd in the blood were not statistically significant compared to the controls (p > 0.05). These results suggest that lead may be genotoxic and the human lymphocyte micronucleus test can be used to assess genotoxic effects that result from occupational exposures. PMID- 11762537 TI - Reliability and validity of three-dimensional fetal brain volumes. AB - OBJECTIVE: To determine the intraobserver and interobserver variability in calculating three-dimensional fetal brain volumes and to examine the relationship between these volumes and biparietal diameter and head circumference measurements and estimated gestational age. METHODS: Eighty-five subjects between 16 and 40 completed weeks' gestation participated in the Institutional Review Board approved study. Fetal head images were obtained axially and stored on a magnetic optical disk. The fetal brain volumes were calculated in triplicate by each of 2 observers using 8 to 10 coronal cuts. The coefficient of variation was determined for both physicians. Pearson correlations and linear regression were used to evaluate the relationship between three-dimensional head volume and standard biparietal diameter and head circumference measurements and estimated gestational age. RESULTS: The coefficients of variation were low for both investigators, at 2.04% and 2.44%. The correlations between fetal brain volumes and biparietal diameter, head circumference, and estimated gestational age were all highly significant (P < .001). The linear regression of brain volumes with estimated gestational age was also highly significant (P < .001). CONCLUSIONS: Three dimensional fetal brain volume measurements had excellent intraobserver and interobserver reliability. The volumes correlated very well with standard biparietal diameter and head circumference measurements. These volumes can also be used to determine estimated gestational age. PMID- 11762538 TI - Three-dimensional sonographic assessment of fetal behavior in the early second trimester of pregnancy. AB - OBJECTIVE: To evaluate the fetal behavior pattern in the early second trimester of pregnancy by use of specially developed abdominal dynamic three-dimensional sonography. METHODS: Dynamic three-dimensional sonographic examinations were performed on 11 healthy pregnant women at 14 to 18 weeks of gestation. This imaging system provided continuous three-dimensional sonographic images every 1 to 2 seconds. Fetal movements were recorded continuously for 60 minutes in each fetus. The rate of occurrence of head, mouth, arm, trunk, and leg movements was evaluated. All fetal behavioral patterns were observed during the period studied. RESULTS: The active phase (time with fetal movements) was 59.4%, and the resting phase was 40.6%. The most active fetal behavior pattern was an arm movement, whereas the least was a mouth movement. Moreover, each fetal movement was synchronized and harmonized with other fetal movements (a few movement patterns were found to be generated simultaneously). CONCLUSIONS: Dynamic three dimensional sonography provides a novel means for evaluation of fetal behavior in the early second trimester of pregnancy. These results suggest that dynamic three dimensional sonography may be an important modality in future early fetal behavior research and in evaluation of early fetal well-being. PMID- 11762539 TI - Spectrum of normal intrauterine cavity sonographic findings after first-trimester abortion. AB - OBJECTIVE: To characterize the sonographic appearance of the uterine cavity after uncomplicated first-trimester abortion. METHODS: Women who underwent uterine evacuation for first-trimester abortion were referred for endovaginal sonographic examination within the week after the procedure. Special attention was directed to characterizing the intrauterine cavity. Demographic and clinical parameters were collected. A repeated postmenstrual examination was carried out in selected cases. RESULTS: In all, 57, 10, and 7 sonographic examinations were performed after termination of pregnancy, incomplete (spontaneous) abortion, and missed abortion, respectively. Fifty-seven (77%) of the 74 examinations showed considerable amounts of intrauterine content with various echogenicities (anteroposterior thickness range, 7-61 mm). No association could be documented between the pattern of appearance and gravidity, parity, gestational age, or type of abortion procedure. All postmenstrual reevaluations of patients with excessive amounts of intrauterine material at the initial examination (n = 7) showed empty intrauterine cavities. CONCLUSION: Within the week after first-trimester abortion, the uterine cavity is seldom empty. Thick heterogeneous material is an expected finding after examination. By being familiar with this normal range of appearances, clinicians can avoid unnecessary repeated invasive evacuation procedures. A follow-up sonographic evaluation during the follicular phase of the next menstrual cycle is recommended to confirm the absence of retained products of pregnancy. PMID- 11762540 TI - Birth weight prediction by three-dimensional ultrasonography: fractional limb volume. AB - OBJECTIVE: To introduce fractional limb volume as a new ultrasonographic parameter, validate reliability of fractional limb volume measurements, develop new birth weight prediction models, and examine their practical utility for estimating fetal weight during late pregnancy. METHODS: Healthy late-third trimester fetuses were prospectively scanned by two- and three-dimensional ultrasonography within 4 days of delivery. Volume data sets were subsequently used to extract several standard ultrasonographic measurements. Fractional limb volumes of the upper arm and thigh were based on 50% of diaphyseal bone length. Intraclass correlation was used to analyze interobserver and intraobserver reliability of fractional limb volume measurements. Several weight prediction models were developed by linear regression analysis. New prediction models were prospectively compared with the Hadlock formula in 30 healthy late-third trimester fetuses. RESULTS: One hundred fetuses were scanned at a mean +/- SD menstrual age of 39.2 +/- 1.2 weeks. Intraclass correlation indicated a significant degree of interobserver and intraobserver reliability for fractional thigh volume. Fractional thigh volume (r = 0.86), fractional upper arm volume (r = 0.83), abdominal circumference (r = 0.83), and midthigh circumference (r = 0.82) were most highly correlated with birth weight. The best prediction model (abdominal circumference and fractional thigh volume) gave weight estimates that deviated from actual birth weight by -0.025% +/- 7.8%. For late-third-trimester fetuses, the Hadlock model yielded errors of 9.0% +/- 9.0%. Prospective testing confirmed superior performance of the new prediction model, which gave accuracy of 2.3% +/- 6.6% (Hadlock method, 8.4% +/- 8.7%). It correctly predicted 20 of 30 birth weights to within 5% of actual weight. By comparison, the Hadlock model predicted only 6 of 30 birth weights to within 5% of actual weight. CONCLUSIONS: A new birth weight prediction model, based on fractional thigh volume and abdominal circumference, is reliable during the late third trimester. It provides a means for including soft tissue evaluation for birth weight prediction. This rapid technique avoids technical limitations that currently hinder the practical implementation of three-dimensional ultrasonography for estimating birth weight. PMID- 11762541 TI - Lack of association between carotid artery volume blood flow and cardiac output. AB - OBJECTIVE: The correlation of cardiac output and cerebral perfusion is unclear. We tested this potential association by correlating cardiac output data obtained by echocardiography and cerebral blood flow data as determined by color M-mode measurements of carotid artery blood flow. METHODS: We studied 43 patients with a broad spectrum of cardiac performance by means of transthoracic echocardiography. In these patients, different cardiac indices such as stroke volume, ejection fraction, and heart minute volume were determined. The data were correlated with volumetric flow measurements (color M-mode duplex system) of the common carotid arteries bilaterally. RESULTS: Heart minute volume ranged from 1.632 to 9.836 mL/min (mean +/- SD, 4.652 +/- 1.621 mL/min); ejection fraction ranged from 18% to 76% (mean, 48% +/- 16%). The relative fraction of carotid volume flow compared with heart minute volume was 15% +/- 6%. There was no correlation between ejection fraction, stroke volume, or heart minute volume and absolute volume flow in the carotid arteries when being adjusted for age. There was a highly significant inverse correlation (r = -0.8; P < .0001) of the relative fraction of the carotid volume flow (carotid volume flow/heart minute volume [percent]) and the heart minute volume. CONCLUSION: Our data support the concept that cerebral blood flow is independent of cardiac output. PMID- 11762542 TI - Quantification of flow volume with a new digital three-dimensional color Doppler flow approach: an in vitro study. AB - OBJECTIVE: The quantification of flow stroke volume is important for evaluation of patients with cardiac dysfunction and cardiovascular disease. Three dimensional digital color Doppler flow imaging allows the acquisition of flow data in an orientation approximately parallel to flow and analysis of the Doppler flow velocities perpendicular to flow (cross-sectional flow calculation). This in vitro study assessed the applicability of this method for quantifying cardiac output in a funnel-shaped tube model similar to mitral inflow or the left ventricular outflow tract. METHODS: A new digital three-dimensional color Doppler method was used to acquire Doppler flow information. Raw scan line data with digital velocity assignments were obtained on a conventional Doppler color flow imaging system with a 180 degrees rotating multiplanar transesophageal probe connected to a computer workstation. Nine stroke volumes (20-60 mL) with flow rates ranging from 1.5 to 5.28 L/min in a funnel-shaped pulsatile laminar flow model were studied. Three-dimensional flow rates were compared with standard-of reference measurements of flow obtained from timed collection in a graduated cylinder and with an ultrasonic flow meter. RESULTS: Within the funnel tube, the flow volumes that were calculated from the first, second, and third depths and the average of all 3 depths correlated well with the actual flow rate (r = 0.97 0.99). Results from the middle and second levels and from the average of all 3 depths provided the closest fit to the actual flow rates (r = 0.99; y = 0.96x + 0.14; and r = 0.98; y = 1.14x - 0.43, respectively). CONCLUSIONS: Although a work in progress, this digital three-dimensional color Doppler flow measurement method is feasible, accurate, and simple, and it may offer in vivo evaluation of blood volume flow given a favorable orientation between the valve orifice and the scanning device. PMID- 11762543 TI - Effectiveness of transcranial and transthoracic ultrasound and microbubbles in dissolving intravascular thrombi. AB - OBJECTIVE: To examine the effectiveness of 1 -MHz and 40-kHz ultrasound with and without microbubbles in fragmenting thrombi in attenuated conditions. METHODS: First, an vitro transcranial model was used to examine the ability of these frequencies to fragment thrombi in the presence or absence of perfluorocarbon exposed sonicated dextrose albumin microbubbles. Second, an in vivo transthoracic model was used to test the effectiveness of these same frequencies with intravenous perfluorocarbon-exposed sonicated dextrose albumin in fragmenting left circumflex coronary thrombotic occlusions. RESULTS: In the in vitro model, both transcranial 1-MHz and 40-kHz ultrasonic frequencies were effective at fragmenting thrombi only in the presence of microbubbles. In the in vivo model, 1 MHz ultrasound with intravenous perfluorocarbon-exposed sonicated dextrose albumin angiographically recanalized only 4 of 14 occlusions but was consistently effective at improving myocardial blood flow to the risk area even in the absence of angiographic recanalization. Both 40-kHz and 1-MHz ultrasound with perfluorocarbon-exposed sonicated dextrose albumin improved regional wall thickening and electrocardiographic abnormalities (P < .05 compared with control or ultrasound alone). CONCLUSIONS: Transcranial and transthoracic ultrasound in the presence of intravenous microbubbles can improve flow to ischemic regions and should be considered as a supplement to current pharmacologic therapy. PMID- 11762544 TI - Pattern of Doppler flow indices at the carotid bifurcation: evaluation by hemodynamic color Doppler imaging. AB - OBJECTIVE: To visualize the spatial variation of Doppler indices, principally the pulsatility index, taken proximal to the carotid bifurcation and to evaluate their relationship to the geometry of the carotid bulb. METHODS: The pattern of ultrasonographic Doppler indices was studied in healthy volunteers by using hemodynamic color Doppler imaging, which computes and displays a Doppler index at each color pixel from a sequence of color Doppler image frames taken over several cardiac cycles. RESULTS: In carotid bulbs with laminar flow (n = 5), the spatial partitioning between low-resistance internal carotid artery and high-resistance external carotid artery flows could be followed over 5 cm upstream in the common carotid artery. However, normal reverse or vortex flows at the carotid bulb (n = 15) obliterated upstream flow partitioning within 2 cm of the flow divider The pulsatility index was neither laterally nor axially uniform in the common carotid artery. CONCLUSIONS: Localization of "core flow" where meaningful Doppler indices may be measured is determined by the expansion geometry of the carotid bulb and usually requires positioning of a small sample volume in the center of the lumen at least 3 cm upstream from the flow divider However, in the absence of reverse or vortex flows, placement of a spectral Doppler sample volume is best guided by hemodynamic color Doppler imaging. PMID- 11762545 TI - Usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax. AB - OBJECTIVE: The suspended microbubble sign is defined as the image seen on ultrasonography consisting of a pleural effusion strewn with numerous hyperechoic pinpoints and more or less linear shadows that move synchronously with respiration. In this study, we intended to evaluate the clinical usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax. METHODS: This series consisted of 8 patients with empyemic hydropneumothorax and 23 patients with nonempyemic hydropneumothorax. The finding of the presence of the suspended microbubble signs on ultrasonography was recorded. To further elucidate the generation of the suspended microbubble sign, the interaction between air and pleural fluid of different types was investigated in vitro. RESULTS: The suspended microbubble sign was shown on ultrasonography in all 8 patients with empyemic hydropneumothorax but was absent in the 23 patients with nonempyemic hydropneumothorax. These findings were supported by the observation that the pus seemed to mix with and trap the air more easily than did the nonpurulent pleural fluid, as shown in vitro. In this selected population, the sensitivity and specificity of the suspended microbubble sign in aiding a diagnosis of empyemic hydropneumothorax were both 100%. CONCLUSION: The suspended microbubble sign shown on ultrasonography might be of considerable value in differentiating empyemic and nonempyemic hydropneumothorax. PMID- 11762546 TI - Role of Doppler sonography in the evaluation of accessory spleens after splenectomy. AB - OBJECTIVE: Splenectomy influences the Doppler blood flow pattern in the splenic artery. Blood flow in this vessel might return to normal if an accessory spleen increases in size after splenectomy. Our objective was to evaluate the resistive index of the splenic artery depending on the presence or absence of a hypertrophic accessory spleen in splenectomized patients. METHODS: The resistive index of the splenic artery was evaluated by duplex Doppler sonography in 19 splenectomized patients (8 with a hypertrophic accessory spleen) and in 8 healthy volunteers. The resistive index was measured within 3 cm of the origin of the splenic artery, and 3 different measurements were averaged. The presence or absence of a hypertrophic accessory spleen was diagnosed on the basis of sonography, computed tomography, magnetic resonance imaging, or scintigraphy, as well as by the presence or absence of Howell-Jolly bodies on a peripheral blood smear. RESULTS: The resistive index of the splenic artery in the splenectomized patients without a hypertrophic accessory spleen (mean +/- SD, 0.82 +/- 0.06; n = 11) was significantly (P < or = .0001) higher than in splenectomized patients with a hypertrophic accessory spleen (0.63 +/- 0.06; n = 8) and in control subjects (0.63 +/- 0.05; n = 8). CONCLUSIONS: In the splenectomized patient, a hypertrophic accessory spleen is associated with a normal resistive index in the splenic artery. PMID- 11762547 TI - Deep femoral artery pseudoaneurysm due to brucellosis. PMID- 11762548 TI - Three-dimensional sonographic imaging of a highly developed fetus in fetu with spontaneous movement of the extremities. PMID- 11762549 TI - Use of three-dimensional ultrasonography for prenatal diagnosis of ambiguous genitalia. PMID- 11762550 TI - Congenital glioblastoma multiforme: prenatal diagnosis on the basis of sonography and magnetic resonance imaging. PMID- 11762551 TI - Imaging the human corpus luteum. PMID- 11762552 TI - Hydatid liver cyst treatment. PMID- 11762553 TI - Evaluation of student achievement and educational outcomes. AB - Development of problem-solving skills is vital to professional education as is factual recall. Student mastery must be measured to document student achievement requiredfor completion of educational requirements and professional certification. These measurements also help determine if the educational process is meeting its goal of helping students develop critical cognitive skills for therapeutic problem solving. Testing student growth in the ability to solve problems is less understood. Stressing integration of information across disciplines to derive answers is also important. Test items should resemble the real-world task that students are expected to master. Thatisreallythe essence of content validity, which means faculty should be biased toward presenting information that way. This article is based on a symposium presented at the annual meeting of the American College of Clinical Pharmacology in September 1996. Symposium goals were to define purposes and uses of student evaluations by type and format, including application of techniques that improve evaluation, precision, and validity. Technical applications of computer-based learning and evaluation of problem-solving skills are described. Actual experience with evaluation of problem solving in the curriculum is discussed. The process by which a medical school developed and implemented an evaluation system for a new problem-based curriculum is presented, followed by a critique of the successes and problems encountered during the first year of implementation. Criteria that a well-constructed evaluation program must meet are explored. The approach and philosophy of national standardized testing centers are explained. PMID- 11762554 TI - P-glycoprotein (P-gp) is upregulated in peripheral T-cell subsets from solid organ transplant recipients. AB - Immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus, and corticosteroids are substrates for the transmembrane multidrug resistance pump P glycoprotein (P-gp). Experience in oncologyhas suggested that chronic exposure to P-gp substrates induces upregulation of P-gp activity, which could result in resistance to immunosuppressive drugs. The authors investigated P-gp function in CD4+ and CD8+ T cells from the peripheral blood of solid organ transplant recipients (SOTX). Subjects included 14 stable SOTX (10 liver, 4 lung) and 16 healthy controls. Four-color flow cytometry was used to simultaneously measure intracellular concentration of the fluorescent P-gp substrate Rhodamine 123 (Rh123) and surface expression of CD45RO (nominal memory/effector), CD45RA (naive), and either CD4 or CD8. P-glycoprotein function was measured by a dye efflux assay in which activity was inferred from a decrease in Rh123 fluorescence. CD4+ and CD8+ T cells from patients and control subjects eliminated Rh123, and this activity was inhibited by verapamil, a known P-gp substrate. CD8+ T cells had greater P-gp activity than CD4+ cells, and naive and transitional T cells displayed greater activity than memory T cells. Activity was bimodal in CD8+ CD45RO+ T cells, with a subset of these cells expressing the greatest P-gp activity. Patient CD8+ naive and transitional T cells had upregulated P-gp activity compared to control subjects. We conclude that (1) P-gp activityis significantly upregulated in specific T-cell subsets (CD8+/CD45RA+) in the peripheral blood of SOTX, and (2) the bimodal nature of P-gp response in CD8+ T cells complicates analysis of the effect of chronic administration of P-gp substrates to SOTX. PMID- 11762555 TI - Pharmacodynamics and pharmacokinetics of omapatrilat in heart failure. AB - The purpose of this study was to determine the pharmacodynamics and pharmacokinetics of omapatrilat, administered orally (25 mg) or intravenously (10 mg) in 19 New York Heart Association class II and class III congestive heart failure (CHF) patients versus 17 healthy controls matched for age, race, gender, and weight. The plasma concentrations of atrial natriuretic peptide (ANP) increased by approximately 20% and 30% in CHF and control subjects, respectively, at 4 hours after intravenous or oral omapatrilat administration. Similar elevation in the cyclic guanosine monophosphate concentration (25% to 35%) and ANP urinary excretion (21 ng/24 h to 22 ng/24 h) was seen in all treatment groups after omapatrilat administration. Angiotensin-converting enzyme activity was > 90% inhibited at 4 hours after dosing and remained approximately 60% to 70% inhibited at 24 hours after dosing. The levels of endothelin-1 and endothelin-2 remained unchanged after oral or intravenous administration of omapatrilat. The maximal reduction in seated blood pressure compared with baseline was similarfor CHF and control subjects. Clinical pharmacokinetic parameters were similar in both groups after intravenous dosing, but maximum concentration and area under the concentration-time curve were elevated in CHF patients compared with controls after oral dosing. Omapatrilat was well tolerated; differences in systemic exposure and metabolism between CHF patients and controls did not appear to be clinically significant. PMID- 11762556 TI - Omapatrilat: neurohormonal and pharmacodynamic profile when administered with furosemide. AB - Pharmacodynamic effects of combination therapy with omapatrilat and furosemide were evaluated. Two groups of 13 healthy subjects each received furosemide 20 mg dailyfor 15 days coadministered with either placebo on days 6 to 15 or omapatrilat 10 mg on days 6 to 10 and 25 mg on days 11 to 15. In the omapatrilat group, urinary excretion of atrial natriuretic peptide increased, and greater blood pressure reductions were seen compared with placebo. Concomitant omapatrilat treatment did not affect the acute diuresis, natriuresis, and kaliuresis observed with chronic administration of furosemide. Neither effective renal plasma flow nor glomerularfiltration rate changed in either treatment group. No clinically significant safety issues were observed. Daily coadministration of omapatrilat 10 or 25 mg with furosemide 20 mg does not affect the pharmacodynamics offurosemide at steady state. PMID- 11762557 TI - Pharmacokinetics of norelgestromin and ethinyl estradiol delivered by a contraceptive patch (Ortho Evra/Evra) under conditions of heat, humidity, and exercise. AB - The objectives of this randomized, open-label, three-period, incomplete block design study were to evaluate the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE) delivered by the contraceptive patch, Ortho Evra/Evra, and to evaluate patch adhesion under conditions of heat, humidity, and exercise. During each treatment period, 30 healthy women wore Ortho Evra on the abdomen for 7 days under one of six conditions (normal activity, sauna, whirlpool, treadmill, cool water immersion, or a combination of activities). Blood samples were collected before and several times to 240 hours after patch application. Mean serum concentrations of NGMN and EE generally remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the 7-day wearperiodfor all activities. Only 1 (1.1%) of 87 patches completely detached spontaneously. Peel force measurements were comparable for all activities. Ortho Evra was well tolerated. In conclusion, Ortho Evra delivers efficacious concentrations of NGMN and EE and maintains adhesive reliability through 7 days of wear even under conditions of heat, humidity, and exercise. PMID- 11762558 TI - The effect of intravenous haloperidol on QT interval dispersion in critically ill patients: comparison with QT interval prolongation for assessment of risk of Torsades de Pointes. AB - The objective of this study was to determine the effect of intravenous haloperidol on QT interval dispersion in critically ill patients and to compare increases in QT interval dispersion and QTc intervals in patients who developed haloperidol-induced Torsades de Pointes versus those in patients who did not. This was a case-controlled study of 30 critically ill patients who received intravenous haloperidol for delusional agitation. Cases were patients (n = 6) who developed Torsades de Pointes during haloperidol therapy. Controls were patients (n = 24) who did not experience haloperidol-induced Torsades dePointes. QTc intervals were measured and QT interval dispersion was calculated. Haloperidol prolonged QTc interval compared to pretreatment values in Torsades de Pointes patients (606 +/- 61 ms vs. 501 +/- 44 ms, p = 0.007) by a greater magnitude than in patients who did not experience Torsades de Pointes (507 +/- 60 ms vs. 466 +/- 44, p = 0.01). Twelve-lead analysis revealed that QT interval dispersion increased in patients who experienced Torsades de Pointes (from 63 +/- 11 to 95 +/- 22 ms, p = 0.03) but not in those who did not (62 +/- 18 vs. 60 +/- 26 ms, p = 0.66). Analysis of precordial leads only showed no significant haloperidol associated increases in QTinterval dispersion in eithergroup. The odds of developing haloperidol-induced Torsades de Pointes were highest in patients with QTc interval > 521 ms during haloperidol therapy(odds ratio = 12.1). It was concluded that intravenous haloperidol prolongs QTc intervals in critically ill patients. The degree of prolongation is greater in patients who experience Torsades de Pointes. QT interval dispersion may be increased in patients who develop haloperidol-induced Torsades de Pointes compared with those who do not. However, these effects are dependent on the method of measurement (12 leads vs. precordial leads). In addition, the odds of haloperidol-induced Torsades de Pointes are higherin patients with QTc intervalprolongation compared with increased QT interval dispersion. Therefore, QTc interval determination remains preferable to QT interval dispersion as a means assessment of risk for haloperidol-induced Torsades de Pointes. PMID- 11762559 TI - Pharmacokinetics of intravenous itraconazole followed by itraconazole oral solution in patients with human immunodeficiency virus infection. AB - This randomized, open-label, comparative study assessed the pharmacokinetics and safety of intravenous and oral hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions of itraconazole in patients with advanced human immunodeficiency virus (HIV) infection. All patients received 1-hour intravenous infusions of itraconazole 200 mg twice dailyfor 2 days, then once dailyfor 5 days. Patients were then randomized to receive itraconazole oral solution, 200 mg twice daily or 200 mg once daily, for a further 28 days. Itraconazole was solubilized by HP-beta CD in both intravenous and oral solutions, so HP-beta-CD concentration in plasma was measured. Thirty-two patients were enrolled and analyzed (n = 32 for intravenous treatment, 32 completed; n = 16 for oral once daily, 15 completed; n = 16 for oral twice daily, 12 completed). Steady-state plasma concentrations of itraconazole and hydroxyitraconazole were reached by days 3 and 6, respectively. After intravenous dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were 906 ng/ml and 1,690 ng/ml, respectively. During oral dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were maintained or increased in the 200 mg twice-dailygroup but fell with the 200 mg once-daily oral dose. Itraconazole was generally well tolerated and had a favorable safetyprofile; minor changes in hematology variables were noted during the intravenous phase, and HP-beta-CD was cleared rapidly, mostly in urine. Twenty-eight patients (88%) experienced at least one adverse event; no adverse event was severe, and only seven were definitely related to itraconazole. In conclusion, itraconazole 200 mg given intravenously twice daily for 2 days, then once daily for 5 days, rapidly achieves amean steady-state trough concentration of itraconazole of over 250 ng/ml, which is associated with clinic outcome and is effectively maintained with itraconazole oral solution 200 mg twice daily in patients with advanced HIV infection. PMID- 11762560 TI - Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler dry-powder inhalers to healthy subjects. AB - Direct comparisons of the pharmacokinetic (PK) and systemic pharmacodynamic (PD) properties of inhaled corticosteroids after single and multiple dosing in the same subjects are scarce. The objective of this study was to compare thePK/PDproperties of clinically equivalent, single, and multiple doses of dry powder formulations of inhaled fluticasone propionate (FP 200 and 500 microg via Diskus) and budesonide (BUD, 400 and 1,000 microg via Turbohaler). Fourteen healthy subjects completed a double-blind, double-dummy, randomized, placebo controlled, five-way crossover study consisting of a single dose administered at 8 a.m. on day 1 followed by 4 days of twice-daily dosing at 8 a.m. and 8 p.m. on days 2 to 5. Serum concentrations of FP and BUD were measured using validated liquid chromatography/ mass spectrometry assays. The 24-hour cumulative cortisol suppression (CCS) in serum was monitored as the pharmacodynamic surrogate marker. Peak serum concentrations following single and multiple dosing were observed 10 to 30 minutes after inhalation for BUD and 30 to 90 minutes afterinhalation of FP with no influence of dose ordosingregimen. After a single dose of 1000 microg BUD and 500 microg FP the median estimates of terminal half-life and mean residence time were 3.5 and 3.9 hours for BUD and 10.1 and 12.0 hours for FP, respectively. Using previously reported intravenous data, the mean absorption times (MAT) were calculated to be around 2 hours and 7 hours for BUD and FP respectively. On average, the area under the curve (A UC) at steady state (day 5) was up to 30% higher for BUD compared to that over a 12-hour period following the first dose on day 1, whereas A UC estimates were 50% to 80% higherforFP at steady state, indicating accumulation. However, the steady-state Cmax values were seven to eight times and AUC values three to four times higher for BUD than for FP. Comparison of active treatment data with placebo showed that CCS after a single dose was not pronounced for any of the doses/drugs studied. On day 5, both doses of BUD caused statistically significant suppression (CCS of 19% for the 400 microg dose and 36% for the 1,000 microg dose). For FP only the high dose had a statistically significant effect on serum cortisol (CCS of 14% for the 200 microg dose and 27% for the 500 microg dose). Compared to BUD, FP has slower pulmonary absorption and slower elimination kinetics. However, following inhalation of therapeutically equipotent, multiple twice-daily doses in healthy subjects, the systemic effects of FP delivered via Diskus on AUC24 serum cortisol were relatively low and similar to those of BUD delivered via Turbohaler. PMID- 11762561 TI - Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers. AB - The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle. Female volunteers (n = 16) with a regular menstrual cycle (28 +/- 4 days) received a single oral dose of 80 mg eletriptan during each of the four cycle phases: phase 1 (menses), days 1 to 4; phase 2 (follicular), days 6 to 10; phase 3 (ovulatory), days 11 to 13; and phase 4 (luteal), days 21 to 24. Eletriptan plasma concentrations were determined from serial plasma samples taken during a 24-hourperiod after dosing. Blood pressure, pulse rate, and ECG measurements were performed at baseline, 1 and 24 hours after dosing. No significant differences between phases were observed for maximum plasma concentration (cmax, range of means = 188-234 ng/ml), time to maximum concentration (tmax, range of means = 1.8-2.5 h), or systemic exposure (area under the curve [AUC], range of means = 1194-1514 ng x h/ml). Although there was a statistically significant difference in the terminal phase elimination rate constant (kel) between phases 1 and2 (0.175/h vs. 0.158/h, p = 0.044), the corresponding difference in terminal phase half-life (t 1/2) (4.0 h vs. 4.4 h) was not considered to be clinicallyrelevant. No clinically relevant differences in blood pressure, pulse rate, or ECG were observed, and the incidence, nature, and severity of adverse events were similar in all phases. The different phases of the menstrual cycle had no clinically significant effect on the pharmacokinetics, safety, or tolerability of oral 80 mg eletriptan in healthy females. PMID- 11762562 TI - Effect of food and food composition on alcohol elimination rates in healthy men and women. AB - Several studies have evaluated the effect of food on alcohol pharmacokinetics; however, most studies have used oral alcohol administration, which cannot separate the influence of food on absorption from its influence on alcohol elimination. Alcohol clamping uses intravenous alcohol and provides a direct measure of the alcohol elimination rate (AER). Two studies, using alcohol clamping at 50 mg %, were conducted to investigate the effect of food and food composition on AER (g/h) in healthymen and women. In the first study, 20 subjects underwent two clamping sessions, one after a 12-hour fast and another 1 hour after consuming a 530-calorie breakfast. In the second study, 8 subjects underwent four clamping sessions: one after a 12-hour fast and, in each of three "fed" sessions, 1 hour after a 550-calorie high-fat, high-protein, or high carbohydrate breakfast. Comparison of AERs from the first study showed an average 25% increase following food compared to thatfollowingfasting. Men showed significantly higher AERs compared to women; however, the food effect was similar in both genders. In the second study, the AER showed a significant average 45% increase following the meal, regardless of composition, compared with that following fasting. These findings indicate that food intake results in increased alcohol elimination rates. The increase was similar for meals of different compositions, suggesting that the food effect is not due to specific interactions with meal constituents. Probable mechanisms for the increased alcohol elimination includefood-induced increases in hepatic blood flow and in the activity of alcohol-metabolizing enzymes. PMID- 11762563 TI - Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults. AB - A 21-day, open-label, multisite, dose escalation study comprising three demographic groups (children, adolescents, and adults) was performed to determine the pharmacokinetics and tolerability of orally administered buspirone. Thirteen children and 12 adolescents with anxiety disorder and 14 normal healthy adults were escalated from 5 to 30 mg buspirone bid over the 3-week study. Pharmacokinetic analysis revealed that buspirone was rapidly absorbed in all study groups, reaching peak levels at about 1 hour after administration. Peak plasma buspirone concentrations (Cmax) were highest in children and lowest in adults at all three dose levels (7.5, 15, 30 mg bid). However, 1 pyrimidinylpiperazine (1-PP), the primary metabolite of buspirone, exhibited a different plasma concentration-time profile; Cmax was significantly higher in children than in either adolescents or adults at all concentrations. In addition, TAUC0-T for 1-PP was significantly higher in the children cohort relative to adolescents and adults. Buspirone was generally safe and well tolerated at doses up to 30 mg bid in adolescents and adults and most of the children. The most frequently reported adverse events in children and adolescents were lightheadedness (68%), headache (48%), and dyspepsia (20%); 2 children withdrewfrom the study at the higher doses (15 mg and 30 mg bid) due to adverse effects. In adults, the most common adverse effect was somnolence (21.4%); lightheadedness, nausea, vomiting, and diarrhea were also reported, although these were mild in intensity. PMID- 11762564 TI - The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration. AB - The first-dose pharmacokinetics of midazolam and its primary alpha hydroxymetabolite were studied after single-dose administration. Eligible study patients were enrolled into one of three study arms: Arm I (midazolam/metabolite pharmacokinetic evaluation after oral administration of a syrup formulation), Arm II (the absolute bioavailability of midazolam syrup), and Arm III (midazolam and metabolite pharmacokinetics after IV administration). Complete blood sampling for pharmacokinetic analysis was available in 87 subjects. Midazolam absorption after administration of the oral syrupformulation was rapid, with adolescents absorbing the drug at approximately half the rate observed in younger children (ages 2 to < 12 years). Furthermore, midazolam t 1/2 was prolonged and CL/F reducedin adolescents as compared with younger children. Although the midazolam Vd/F appeared larger in the youngest age group after oral administration, this observation was not apparent after IV dosing, suggesting subject differences in bioavailability rather than distribution. Like midazolam, the disposition characteristics for a-hydroxymidazolam were also highly variable, with the greatest formation of metabolite (reflected by the AUC ratio) observed in children ages 2 to < 12 years. The A UC ratios of alpha-hydroxymidazolam to midazolam after IV dosing were similar across all age groups and were smaller than corresponding values following oral administration. The absolute bioavailability of midazolam averaged 36% with a very broad range (9%-71%). No relationship between midazolam bioavailability and age was observed. Overall, the disposition characteristics of midazolam and its a-hydroxy metabolite were highly variable, appeared independent of age and dose administered, and were linear over the dose range studied (0.25 to 1 mg/kg). These data suggest that an initial oral dose of 0.2 to 0.3 mg/kg should be adequateforsuccessful sedation of most pediatric patients. The inherent variability in midazolam bioavailability and metabolism underscores the importance of titrating midazolam dose to desired effect. PMID- 11762565 TI - Error and blame: the Winnipeg inquest. PMID- 11762566 TI - The cost of maintaining adequate antidote supplies. PMID- 11762567 TI - Personalized medications. PMID- 11762568 TI - Give us clear, not convoluted, clinical practice guidelines. PMID- 11762569 TI - Give us clear, not convoluted, clinical practice guidelines. PMID- 11762570 TI - Probiotics as medical therapies. PMID- 11762571 TI - How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. AB - BACKGROUND: Numerous small clinical trials have been carried out to study the behaviourally defined efficacy and safety of short-acting methylphenidate compared with placebo for attention-deficit disorder (ADD) in individuals aged 18 years and less. However, no meta-analyses that carefully examined these questions have been done. We reviewed the behavioural evidence from all the randomized controlled trials that compared methylphenidate and placebo, and completed a meta analysis. METHODS: We searched several electronic sources for articles published between 1981 and 1999: MEDLINE, EMBASE, PsychINFO, ERIC, CINAHL, HEALTHSTAR, Biological Abstracts, Current Contents and Dissertation Abstracts. The Cochrane Library Trials Registry and Current Controlled Trials were also consulted. A study was considered eligible for inclusion if it entailed the following: a placebo-controlled randomized trial that involved short-acting methylphenidate and participants aged 18 years or less at the start of the trial who had received any primary diagnosis of ADD that was made in a systematic and reproducible way. RESULTS: We included 62 randomized trials that involved a total of 2897 participants with a primary diagnosis of ADD (e.g., with or without hyperactivity). The median age of trial participants was 8.7 years, and the median "percent male" composition of trials was 88.1%. Most studies used a crossover design. Using the scores from 2 separate indices, this collection of trials exhibited low quality. Interventions lasted, on average, 3 weeks, with no trial lasting longer than 28 weeks. Each primary outcome (hyperactivity index) demonstrated a significant effect of methylphenidate (effect size reported by teacher 0.78, 95% confidence interval [CI] 0.64-0.91; effect size reported by parent 0.54, 95% CI 0.40-0.67). However, these apparent beneficial effects are tempered by a strong indication of publication bias and the lack of robustness of the findings, especially those involving core ADD features. Methylphenidate also has an adverse event profile that requires consideration. For example, clinicians only need to treat 4 children to identify an episode of decreased appetite. INTERPRETATION: Short-acting methylphenidate has a statistically significant clinical effect in the short-term treatment of individuals with a diagnosis of ADD aged 18 years and less. However, the extension of this placebo-controlled effect beyond 4 weeks of treatment has not been demonstrated. Exact knowledge of the extent and definition of the short-term behavioural usefulness of methylphenidate is questioned. PMID- 11762572 TI - Prescription of methylphenidate to children and youth, 1990-1996. AB - BACKGROUND: There are concerns about the frequency and appropriateness of psychostimulant drug prescription to children. In order to identify unusual or unexpected patterns of use or prescribing, we reviewed prescription of methylphenidate (Ritalin) to children and adolescents aged 19 years or less in British Columbia between 1990 and 1996. METHODS: We obtained information about patients, physicians and prescriptions from British Columbia's Triplicate Prescription Program database for controlled drugs. Prescription data were available for the period Jan. 1, 1990, to Dec. 31, 1996. Linkage with the BC Linked Health Dataset provided additional demographic and health information. RESULTS: In 1990, 1715 children received at least 1 prescription for methylphenidate (1.9 per 1000 children). By 1996, the number had increased to 10,881 children (11.0 per 1000). Because some children were prescribed methylphenidate in more than 1 year, we also calculated the frequency with which the drug was prescribed to children who had never received it before. This rate increased from 1.0 per 1000 children in 1990 to 4.7 per 1000 in 1995; the rate fell in 1996 to 3.5 per 1000. The number of children receiving methylphenidate varied across health regions of the province, from 12.0 to 35.4 per 1000. Use also varied by socioeconomic status quintile: in the 2 lowest (least privileged) quintiles, 21.6 per 1000 children received methylphenidate, compared with 18.4 per 1000 in the 3 highest quintiles (relative risk 1.2, 95% confidence interval 1.1-1.2). Pediatricians and psychiatrists wrote 23% and 21% of all prescriptions respectively. General practitioners accounted for 56% of all prescriptions and 41% of initial methylphenidate prescriptions. A claim for prior specialist consultation was found in 30% of such cases. Many of the children who received more than 10 prescriptions had seen 4 or more physicians. The average daily dosage prescribed differed little among general practitioners, pediatricians and psychiatrists, unlike the mean interval between successive prescriptions: 89.9 (standard deviation [SD] 68.2), 99.8 (SD 64.1) and 75.9 (SD 70.2) days respectively. Persistence with therapy was more likely when a psychiatrist provided the initial prescription, or with involvement of more than one specialty. INTERPRETATION: Many trends and practices in the prescription of methylphenidate to children in British Columbia are consistent with other settings and accepted standards. Some aspects warrant closer investigation, including regional and socio-economic discrepancies in the distribution of patients, the relative involvement of primary and specialist care providers, continuity of care issues and time intervals between prescriptions. PMID- 11762573 TI - Past exposure to vaccines and subsequent risk of Alzheimer's disease. AB - BACKGROUND: It has been suggested that changes to the immune system could be a factor in age-related conditions such as Alzheimer's disease. Our objective was to examine the association between past exposure to conventional vaccines and risk of Alzheimer's disease. METHODS: We analyzed data from a representative community sample of subjects 65 years of age or older participating in the Canadian Study of Health and Aging, a prospective cohort study of dementia. Screening and clinical evaluations were done at both baseline and follow-up. Past exposure to vaccines was assessed at baseline by means of a self-administered questionnaire. RESULTS: Of the 4392 eligible subjects who were cognitively unimpaired and for whom vaccine information was available at baseline (in 1991 1992) and who completed follow-up 5 years later (in 1996-1997), 527 were diagnosed as having cognitive impairment or dementia other than Alzheimer's disease and were excluded from these analyses. Of the remaining subjects, 3682 were cognitively unimpaired at follow-up and 183 were newly diagnosed as having Alzheimer's disease. After adjustment for age, sex and education, past exposure to vaccines against diphtheria or tetanus, poliomyelitis and influenza was associated with lower risk for Alzheimer's disease (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.27-0.62; OR 0.60, 95% CI 0.37-0.99; and OR 0.75, 95% CI 0.54-1.04 respectively) than no exposure to these vaccines. INTERPRETATION: Past exposure to vaccines against diphtheria or tetanus, poliomyelitis and influenza may protect against subsequent development of Alzheimer's disease. PMID- 11762574 TI - The modern scientific physician: 8. Educational preparation. PMID- 11762575 TI - Painful inquiries: lessons from Winnipeg. PMID- 11762576 TI - Methylphenidate in the treatment of children with attention-deficit hyperactivity disorder. PMID- 11762577 TI - Statistics and drug utilization: are prescribing rates really that high? PMID- 11762579 TI - Seventy percent of country's FP practices closed to new patients: survey. PMID- 11762578 TI - Clinical nutrition: 2. The role of nutrition in the prevention and treatment of adult osteoporosis. PMID- 11762580 TI - AMA: set standards, not user fees. PMID- 11762581 TI - Quebec's $100-million campaign targets meningococcal disease. PMID- 11762582 TI - In Russia, medical profession plods toward 21st century. PMID- 11762583 TI - Health care spending slowing. PMID- 11762584 TI - User fees if necessary but not necessarily user fees: CFPC. PMID- 11762585 TI - Medical school enrolment rebounds. PMID- 11762586 TI - Early treatment of acute hepatitis C infection may lead to cure. PMID- 11762588 TI - Deposition of biological material for patent protection in biotechnology. PMID- 11762587 TI - Anthrax: walking the fine line between precaution and panic. PMID- 11762589 TI - Biotechnological production of pyruvic acid. AB - Pyruvic acid is an important organic acid widely used in the chemical and drug, as well as agrochemical, industries. Compared with the chemical method, biotechnological production of pyruvic acid is an alternative approach because of the low cost. An overview of biotechnological production of pyruvate, including direct fermentative production employing eukaryotic and prokaryotic microorganisms, production by a resting cell method and an enzymatic method as well as the recovery of pyruvate, is discussed. A multi-vitamin auxotrophic yeast strain, Torulopsis glabrata. has been used in the commercial production of pyruvate; emphasis is therefore placed on the mechanism and characteristics of pyruvate production by this strain. PMID- 11762590 TI - Desulfurization and desulfonation: applications of sulfur-controlled gene expression in bacteria. AB - Inorganic sulfate is the preferred sulfur source for the growth of most microorganisms but, in its absence, many organosulfur compounds can be degraded microbially to provide sulfur. Desulfurization of dibenzothiophene (DBT) by Rhodococcus sp. and of aromatic sulfonates by Pseudomonas sp. has considerable biotechnological potential. Both these pathways require non-flavin-containing FMNH2-dependent monoxygenases (DszC/DszA and SsuD, respectively). FMNH2 is provided from the freely diffusible FMNH2 pool in the cell, and is replenished by specific NAD(P)H:FMN oxidoreductases (DszD and SsuE). Overexpression of the DszD FMN reductase in a heterologous system increases the efficiency of DBT desulfurization but is detrimental to cell growth at high levels. Expression of the sulfonatase that cleaves aromatic sulfonates (surfactants, dyes) is accompanied by synthesis of a thiol-specific antioxidant protein, which may protect the cell from superoxide radicals generated by autoxidation of the reduced flavin. Effective application of DBT desulfurization in the biodesulfurization of crude oil, and of arylsulfonate desulfonation in bioremediation, may require optimization of both flavin reductase levels and antioxidant protection systems within the cell. PMID- 11762591 TI - Biotechnological development of effective phytases for mineral nutrition and environmental protection. AB - Phytases are hydrolytic enzymes that initiate the release of phosphate from phytate (myo-inositol hexakisphosphate), the major phosphorus (P) form in animal feeds of plant origin. These enzymes can be supplemented in diets for food animals to improve P nutrition and to reduce P pollution of animal excreta. This mini-review provides a synopsis of the concept of "ideal phytase" and the biotechnological approaches for developing such an enzyme. Examples of Escherichia coli AppA and Aspergillus fumigatus PhyA are presented to illustrate how new phytases are identified from microorganisms and developed by genetic engineering based on the gene sequences and protein structures of these enzymes. We also discuss the characteristics of different heterologous phytase expression systems, including those of plants, bacteria, fungi, and yeast. PMID- 11762592 TI - Efficient production of saikosaponins in Bupleurum falcatum root fragments combined with signal transducers. AB - An efficient system to produce saikosaponins (saikosaponin-a and -d) in Bupleurum falcatum adventitious root fragments combined with signal transducers was developed. The roots are heterogeneous in terms of size and shape and sometimes form aggregates during cultivation. When the roots were cut to lengths of about 5 mm using a scalpel and cultivated, the root fragments did not form the aggregates, and root growth and saikosaponin production were not inhibited. After screening various signal transducers, it was clear that methyl jasmonate (MeJA) markedly promoted saikosaponin production. By comparing the effect of MeJA and related substances on saikosaponin production, we conclude that both the pentenyl and carboxylmethyl group of MeJA play an important role in the promotion of saikosaponin production. Addition of both 100 microM MeJA and 20 mM CaCl2 to the medium stimulated the content of saikosaponin in the root, with levels reaching 31.7 mg/g-dry root for 15 days of cultivation. A large amount of root fragments were prepared using a blender and cultivated (23 g-dry root/l) with 400 microM MeJA and 20 mM CaCl2, resulting in a high concentration of saikosaponins (747.3 mg/l). PMID- 11762593 TI - Dual-substrate utilization by Bordetella pertussis. AB - To improve the cultivation of Bordetella pertussis and take advantage of the newest techniques in monitoring and control, a quantitative description of substrate utilisation is necessary. Growth of the organism is limited by two main substrates. However neither interactive nor non-interactive modelling seem appropriate. A model that combines essential and enhanced kinetics was developed based on experimental observation. Instead of fitting all model parameters at once, a step-wise experimentation procedure was used. Finally two cultivations showed the accuracy of the model. PMID- 11762594 TI - Effect of enzyme impurities on phenol removal by the method of polymerization and precipitation catalyzed by Coprinus cinereus peroxidase. AB - The removal of phenol by peroxidase-catalyzed polymerization was examined using the Coprinus cinereus peroxidases at different levels of impurity with respect to contamination. The phenol removal efficiency was improved by lowering the peroxidase purity. Acidic and high molecular weight proteins present as impurities in the peroxidase solution had some positive effect on the phenol polymerizing reaction. The residual enzyme activity, either only in the solution or both in the solution and on the precipitate during the polymerizing reaction, was measured. The results indicate that the main effect of impurities in the peroxidase solution was the suppression of the adsorption of peroxidase molecules on the polymerized precipitate. PMID- 11762595 TI - Development of novel whole-cell immunoadsorbents by yeast surface display of the IgG-binding domain. AB - The ZZ domain derived from Staphylococcus aureus, which binds to the Fc part of immunoglobulin G (IgG), was displayed on the cell surfaces of yeast Saccharomyces cerevisiae by cell-surface engineering using the C-terminal half of alpha agglutinin under control of the 5'-upstream region of the isocitrate lyase gene from Candida tropicalis (UPR-ICL). Display of ZZ on the cell surface was confirmed by immunofluorescence microscopy. Enzyme-linked immunosorbent assay (ELISA) and sandwich ELISA using the S. cerevisiae cells displaying ZZ detected IgG and antigen (human serum albumin) down to a concentration of 1-10 ng/ml in both cases. The detection range covered by these assay systems was wide and could be varied by adjusting the amount of cells and reaction times with horseradish peroxidase (HRP) substrate. Moreover, yeast cells displaying ZZ were successfully used for repeated affinity purification of IgG from serum. These results indicate that S. cerevisiae displaying ZZ may constitute novel and genetically renewable whole-cell immunoadsorbents widely applicable to immunoassays and affinity purification. PMID- 11762596 TI - Evaluation of an electrochemical bioreactor system in the biotransformation of 6 bromo-2-tetralone to 6-bromo-2-tetralol. AB - Biotransformation of 6-bromo-2-tetralone (Br-beta-tetralone) to 6-bromo-2 tetralol (Br-beta-tetralol) by yeast cells of Trichosporon capitatum (ATCC 74312) and its partially purified Br-beta-tetralone reductase was evaluated in an electrochemical bioreactor. The biotransformation rates and final product formation were significantly affected by substrate concentration, biomass and electric potential. At 2 g/l of substrate, the initial reaction rate and final product were increased by 35% and 15%, respectively, with -1.5 V of electric potential compared to without electric potential. Additional substrate (2 g/l) provided by pulse feeding to the reaction mixture at different intervals resulted in 2.1 g/l Br-beta-tetralol compared to a total of 1.2 g/l without feeding. However, the increased production was not proportionate to the amount of additionally fed substrate. Increased substrate availability by the addition of 5% (v/v) ethanol resulted in the highest reaction rate and product formation, but addition of ethanol at a concentration higher than 5% decreased the reaction rate. At low biomass, the initial reaction rates were enhanced significantly when electric potential was high, but a higher biomass was necessary to obtain a similar reaction rate when electric potential was reduced. The highest initial reaction rate (59.2 mg/l per min) was achieved with a two-fold biomass concentration of 15.6 g of dry cell weight/l, substrate at 4 g/l and electric potential at -6 V. The conversion of Br-beta-tetralone to Br-beta-tetralol with partially purified Br-beta-tetralone reductase was slow in the presence of electric potential. PMID- 11762597 TI - Improvement in the bioconversion of penicillin G to deacetoxycephalosporin G by elimination of agitation and addition of decane. AB - The bioconversion of penicillin G to deacetoxycephalosporin G (DAOG) using resting cells of Streptomyces clavuligerus could be a very valuable step in the economical production of semisynthetic cephalosporin antibiotics. The extent of the reaction, however, is very low due to inactivation of the ring expansion enzyme deacetoxycephalosporin C synthetase ("expandase") by reaction components. We show that elimination of agitation during the reaction lowers the rate but increases the amount of DAOG produced, presumably because the inactivation requires high levels of oxygen. Many additives to the medium were examined for their effect on the reaction. Clearly, the most effective compound was the organic solvent, decane. PMID- 11762598 TI - Yeast whole-cell biocatalyst constructed by intracellular overproduction of Rhizopus oryzae lipase is applicable to biodiesel fuel production. AB - Yeast whole-cell biocatalysts for lipase-catalyzed reactions were constructed by intracellularly overproducing Rhizopus oryzae lipase (ROL) in Saccharomvces cerevisiae MT8-1. The gene encoding lipase from R. orvzae IFO4697 was cloned, and intracellular overproduction systems of a recombinant ROL with a pro-sequence (rProROL) were constructed. When rProROL from R. oryzae IFO4697 was produced under the control of the 5'-upstream region of the isocitrate lyase gene of Candida tropicalis (UPR-ICL) at 30 degrees C for 98 h by two-stage cultivation using SDC medium (SD medium with 2% casamino acids) containing 2.0% and 0.5% glucose, intracellular lipase activity reached levels up to 474.5 IU/l. These whole-cell biocatalysts were permeabilized by air-drying and used for the synthesis of methyl esters (MEs), a potential biodiesel fuel, from plant oil and methanol in a solvent-free and water-containing system. The ME content in the reaction mixture was 71 wt% after a 165-h reaction at 37 degrres C with stepwise addition of methanol. These results indicate that an efficient whole-cell biocatalyst can be prepared by intracellular overproduction of lipase in yeast cells and their permeabilization. PMID- 11762599 TI - Differential expression of the Trichoderma reesei beta-xylanase II (xyn2) gene in the xylose-fermenting yeast Pichia stipitis. AB - The transcriptional control of two native promoters and one heterologous promoter and the production of a heterologous protein from these promoters were evaluated in the xylose-fermenting yeast Pichia stipitis cultivated on xylose and glucose as carbon sources, using the beta-xylanase II xyn2 gene of Trichoderma reesei. The xyn2 gene open reading frame was fused to the P. stipitis xylose reductase gene (XYL1) promoter, the P. stipitis transketolase gene (TKL) promoter and the Saccharomyces cerevisiae phosphoglycerate kinase gene (PGKI) promoter DNA sequences on episomal plasmids. The plasmids were transformed into Pichia stipitis and gene expression and beta-xylanase production monitored. The XYL1 promoter was shown to be inducible in the presence of xylose, as xyn2 transcription and beta-xylanase activity could be measured when the recombinant strain was cultivated on xylose but not when it was cultivated on glucose. TKL promoter expression was found to be constitutive when either glucose or xylose was used as sole carbon source. The PGK1 promoter did not promote xyn2 transcription in P. stipitis. The molecular size of the recombinant Xyn2 protein produced by P. stipitis was 20.7 kDa, which is similar to that of the native T. reesei Xyn2 protein. This indicates no or minimal glycosylation of the recombinant protein. The recombinant xyn2-expressing strain also yielded twice the amount of biomass yielded by the control strain when cultivated in medium containing 1% birchwood xylan as sole carbon source. PMID- 11762600 TI - Creation of cell surface-engineered yeast that display different fluorescent proteins in response to the glucose concentration. AB - We have successfully created a novel yeast strain able to monitor changes in environmental conditions by displaying either green fluorescent protein (GFP) from Aequorea victoria or blue fluorescent protein (BFP), a variant of GFP, on its cell surface as a visible reporter. For the display of these fluorescent proteins on the cell surface of Saccharomyces cerevisiase, our cell-surface engineering system was utilized. The GAPDH promoter, which is active in the presence of glucose, and the UPR-ICL promoter from Candida tropicalis, which starts to function in the presence of a reduced level of glucose, were employed simultaneously to express the GFP-encoding gene and the BFP-encoding gene, respectively. This cell-surface-engineered yeast strain emitted green fluorescence from the cell surface when sufficient glucose was present in the medium, and blue fluorescence from the same cell surface when the glucose in the medium was consumed. The fluorescent proteins displayed on the cell surface using the different promoters enabled us to monitor the concentrations of intra- and/or extracellular glucose that regulated activation or inactivation of the promoters. This novel yeast strain could facilitate the computerized control of various bioprocesses measuring emitted fluorescence. PMID- 11762601 TI - H+-ATPase defect in Corynebacterium glutamicum abolishes glutamic acid production with enhancement of glucose consumption rate. AB - A mutant of Corynebacterim glutamicum ('Brevibacterium flayum') ATCC14067 with a reduced H+-ATPase activity, F172-8, was obtained as a spontaneous neomycin resistant mutant. The ATPase activity of strain F172-8 was reduced to about 25% of that of the parental strain. Strain F172-8 was cultured in a glutamic-acid fermentation medium containing 100 g/l of glucose using ajar fermentor. It was found that glucose consumption per cell during the exponential phase was higher by 70% in the mutant than in the parent. The respiration rate per cell of the mutant also increased to twice as much as that of the parent. However, the growth rate of the mutant was lower than that of the parent. Under those conditions, the parent produced more than 40 g/l glutamic acid, while the mutant hardly produced any glutamic acid. Instead the mutant produced 24.6 g/l lactic acid as the main metabolite of glucose. Remarkably, the accumulation of pyruvate and pyruvate family amino acids, i.e., alanine and valine, was detected in the mutant. On the other hand, the parent accumulated alpha-ketoglutaric acid and a glutamate-family amino acid, proline, as major by-products. It was concluded that the decrease in the H+-ATPase activity caused the above-mentioned metabolic changes in strain F172-8, because a revertant of strain F172-8, R2-1, with a H+-ATPase activity of 70% of that of strain ATCC14067, showed a fermentation profile similar to that of the parent. Sequence analyses of the atp operon genes of these strains identified one point mutation in the gamma subunit in strain F172-8. PMID- 11762602 TI - Regiospecific effect of 1-octanol on cis-trans isomerization of unsaturated fatty acids in the solvent-tolerant strain Pseudomonas putida S12. AB - The solvent-tolerant bacterium Pseudomonas putida S12, which adapts its membrane lipids to the presence of toxic solvents by a cis to trans isomerization of unsaturated fatty acids, was used to study possible in vivo regiospecificity of the isomerase. Cells were supplemented with linoleic acid (C18:2delta9 cis,delta12-cis), a fatty acid that cannot be synthesized by this bacterium, but which was incorporated into membrane lipids up to an amount of 15% of total fatty acids. After addition of 1-octanol, which was used as an activator of the cis trans isomerase, the linoleic acid was converted into the delta9-trans,delta12 cis isomer, while the delta9-cis,delta12-trans and delta9-trans,epsilon12-trans isomers were not synthesized. Thus, for the first time, regiospecific in vivo formation of novel, mixed cis/trans isomers of dienoic fatty acid chains was observed. The maximal conversion (27-36% of the chains) was obtained at 0.03 0.04% (v/v) octanol, after 2 h. The observed regiospecificity of the enzyme, which is located in the periplasmic space, could be due to penetration of the enzyme to a specific depth in the membrane as well as to specific molecular recognition of the substrate molecules. PMID- 11762603 TI - Co-metabolic degradation of chlorinated hydrocarbons by Pseudomonas sp. strain DCA1. AB - Pseudomonas sp. strain DCA1, which is capable of utilizing 1,2-dichloroethane (DCA) as sole carbon and energy source, was used to oxidize chlorinated methanes, ethanes, propanes, and ethenes. Chloroacetic acid, an intermediate in the DCA degradation pathway of strain DCA1, was used as a co-substrate since it was readily oxidized by DCA-grown cells of strain DCAI and did not compete for the monooxygenase. All of the tested compounds except tetrachloroethylene (PER) were oxidized by cells expressing DCA monooxygenase. Strain DCAI could not utilize any of these compounds as a growth substrate. Co-metabolic oxidation during growth on DCA was studied with 1,2-dichloropropane. Although growth on this mixture occurred, 1,2-dichloropropane strongly inhibited growth of strain DCAI. This inhibition was not caused by competition for the monooxygenase. It was shown that the oxidation of 1,2dichloropropane resulted in the accumulation of 2,3-dichloro 1-propanol and 2-chloroethanol. PMID- 11762604 TI - Microbial community in anaerobic hydrogen-producing microflora enriched from sludge compost. AB - Hydrogen production by thermophilic anaerobic microflora enriched from sludge compost was studied by using an artificial medium containing cellulose powder. Hydrogen gas was evolved with the formation of acetate, ethanol, and butyrate by decomposition of the cellulose powder. The hydrogen production yield was 2.0 mol/mol-hexose by either batch or chemostat cultivation. A medium that did not contain peptone demonstrated a lower hydrogen production yield of 1.0 mol/mol hexose with less formation of butyrate. The microbial community in the microflora was investigated through isolation of the microorganisms by both plating and denaturing gradient gel electrophoresis (DGGE) of the' PCR-amplified V3 region of 16S rDNA. Sixty-eight microorganisms were isolated from the microflora and classified into nine distinct groups by genetic fingerprinting of the PCR-DGGE or by a random amplified polymorphic DNA analysis and determination of the partial sequence of 16S rDNA. Most of the isolates belonged to the cluster of the thermophilic Clostridium/Bacillus subphylum of low G+C gram-positive bacteria. Product formation by most of the isolated strains corresponded to that produced by the microflora. Thermoanaerobacterium thermosaccharolyticium was isolated in the enrichment culture with or without added peptone. and was detected with strong intensity by PCR-DGGE. Two other thermophilic cellulolytic microorganisms, Clostridium thermocellum and Clostridium cellulosi, were also detected by PCR DGGE, although they could not be isolated. These findings imply that hydrogen production from cellulose by microflora is performed by a consortium of several species of microorganisms. PMID- 11762605 TI - Degradation of diphenyl ether herbicides by the lignin-degrading basidiomycete Coriolus versicolor. AB - Under ligninolytic conditions, the white-rot basidiomycete Coriolus versicolor metabolized chloronitrofen (2, 4, 6-trichloro-4'-nitrodiphenyl ether; CNP) and nitrofen (2, 4-dichloro-4'-nitrodiphenyl ether, NIP), which constitute the largest class of commercially produced diphenyl ether herbicides. The pathway of CNP degradation was elucidated by the identification of fungal metabolites upon addition of CNP and its metabolic intermediates. The metabolic pathway was initially branched to form four metabolites--2, 4, 6-trichloro-3-hydroxy-4' nitrodiphenyl ether, 2, 4-dichloro-6-hydroxy-4'-nitrodiphenyl ether, NIP, and 2, 4, 6-trichloro-4'-aminodiphenyl ether--indicating the involvement of hydroxylation, oxidative dechlorination, reductive dechlorination, and nitro reduction. Of these reactions, hydroxylation was relatively major compared to the others. Extracellular ligninolytic enzymes such as lignin peroxidase, manganese peroxidase and laccase did not catalyze the oxidation of either CNP or NIP. Piperonyl butoxide, an inhibitor of cytochrome P450, suppressed fungal oxidation of CNP and NIP to their hydroxylated products. The inhibition resulted in increasing the amount of reductively dechlorinated and nitro-reduced products. These observations strongly suggest that basidiomycetes may possess a mechanism for a strict substrate recognition system and a corresponding metabolic response system to effectively degrade environmentally persistent aromatic compounds. PMID- 11762607 TI - Bringing mental health into the mainstream. PMID- 11762606 TI - Biodegradation of soluble aromatic compounds of jet fuel under anaerobic conditions: laboratory batch experiments. AB - Laboratory batch experiments were performed with contaminated aquifer sediments and four soluble aromatic components of jet fuel to assess their biodegradation under anaerobic conditions. The biodegradation of four aromatic compounds, toluene, o-xylene, 1,2,4-trimethylbenzene (TMB), and naphthalene, separately or together, was investigated under strictly anaerobic conditions in the dark for a period of 160 days. Of the aromatic compounds, toluene and o-xylene were degraded both as a single substrate and in a mixture with the other aromatic compounds, while TMB was not biodegraded as a single substrate, but was biodegraded in the presence of the other aromatic hydrocarbons. Substrate interaction is thus significant in the biodegradation of TMB. Biodegradation of naphthalene was not observed, either as a single substrate or in a mixture of other aromatic hydrocarbons. Although redox conditions were dominated by iron reduction, a clear relation between degradation and sulfate reduction was observed. Methanogenesis took place during the later stages of incubation. However, the large background of Fe(II) masked the increase of Fe(II) concentration due to iron reduction. Thus, although microbial reduction of Fe(III) is an important process, the evidence is not conclusive. Our results have shown that a better understanding of the degradation of complex mixtures of hydrocarbons under anaerobic conditions is important in the application of natural attenuation as a remedial method for soil and groundwater contamination. PMID- 11762608 TI - Three years of cadaveric renal transplantation. AB - AIM: To study patient and graft outcome and donor characteristics in cadaveric renal transplantation. MATERIAL AND METHODS: Fifty nine patients (35 males and 24 females) who underwent cadaveric renal transplantation between Oct'95 and Nov'98 were analysed. The recovery of renal function was correlated with the type and duration of dialysis. The number of rejections, donor characteristics and patient and graft survival was studied. RESULTS: Fifty nine patients were followed for a mean period of 14.58 months (SD 10.73), their age ranged from 17 to 64 years. Ten patients had primary graft failure, out of which four died and six are on maintenance dialysis. Seven died of other causes. Twelve patients had been on CAPD and 47 were on haemodialysis. Recovery of renal function was earlier in the haemodialysis group (mean 19.29 days SD 16.97) than in the CAPD group (31.6 days SD 32.3 days). But the difference was not statistically significant (p=0.36). The age of the donors ranged from 2 to 72 years (mean 42.8, SD 17.3). Seventeen died of CVA, 16 died of head injury, and one died of sedative overdose. Dual kidney transplant was done in nine patients of whom five have adequate graft function. CONCLUSION: Follow up for a mean period of 14.58 months shows patient survival of 81.3% and graft survival 72.8% with no significant difference in recovery of renal function between CAPD and HD groups. Poor results are due to HLA mismatch leading to rejection. The majority of the deaths were related to septicaemia. PMID- 11762609 TI - Mixed connective tissue disease--clinical and immunological profile. AB - AIM OF THE STUDY: To study the clinical and immunological profile of mixed connective tissue disease (MCTD) in rheumatic disease population. METHODS: We retrospectively analyzed 6400 cases of rheumatic disease population who took treatment in the Department of Rheumatology, Madras Medical College, Chennai during the period of 1996 to 1999, in which eight cases fulfilled the preliminary diagnostic criteria of mixed connective tissue disease devised by Kasukawa et al. All eight cases were studied in detail. RESULTS: All cases were females between 23 to 50 years of age. Polyarthritis, Raynaud's phenomenon and sclerodactyly were present in all eight patients. Oesophageal abnormalities, pulmonary changes and myositis were present in six patients. Facial erythema was observed in five patients. Alopecia and oral ulcers were seen in four patients. Two patients had pulmonary hypertension and migraine like headache. One patient had diffuse proliferative glomerulonephritis as an interesting feature by renal biopsy. Pleuritis, pericarditis and trigeminal neuropathy with lower cranial nerve palsies were present in one case each. Immunological tests showed presence of antinuclear antibodies and anti U1 ribonucleoprotein (anti U1RNP) antibodies in all eight patients. CONCLUSIONS: Mixed connective tissue disease should be considered as an important syndrome in any patient who presents with heterogeneous clinical presentation and who do not fit into any definite criteria of systemic connective tissue disorders. PMID- 11762610 TI - Non-diabetic renal disease in patients with type 2 diabetes mellitus. AB - OBJECTIVES: A wide spectrum of non-diabetic renal diseases (NDRD) are reported to occur in patients with type 2 diabetes mellitus. However, the prevalence and nature of NDRD in type 2 diabetics is not widely documented in our country. Therefore, the objectives of this study were to analyse prevalence and spectrum of non-diabetic renal disease in type 2 diabetic patients. METHODS: Two hundred sixty type 2 diabetic with clinical renal diseases were screened for evidence of NDRD, between April 1997 to March 1999. Renal disease other than diabetic nephropathy was found in 32 (12.3%) patients. Their (male 23; female 9) age ranged between 35-72 (mean 54.15+/-10.3) years. The duration of diabetes was < 5 years in 14 (43.7%), between 5-9 years in 8 (25%) and > 10 years in 10 (31.2%) patients. RESULTS: The presenting clinical syndromes were : chronic renal failure 15 (47%), acute nephritic syndrome 6 (18.7%), nephrotic syndrome 5 (15.6%), acute renal failure 4 (12.5%) and rapidly progressive glomerulonephritis (RPGN) in 2 (6.2%) cases. Overall, incidence of glomerular (46.8%) and tubulo-interstitial lesions (53.2%) were almost equal in type 2 diabetes patients. The spectrum of non-diabetic renal diseases includes : primary isolated glomerulopathy 12 (37.5%); mesangioproliferative GN superimposed on diabetic glomerulosclerosis (DGS) in 3 (9.3%); acute tubulo-interstitial nephropathy (TIN) 4 (12.5%); chronic TIN 10 (31.25%) and three patients had chronic pyelonephritis. Diabetic retinopathy was absent in 22 (69%) cases where 10 (31%) patients had background diabetic retinopathy. None of the patients with non-diabetic glomerular disease had diabetic retinopathy, except two who had DGS in addition to mesangioproliferative GN on renal biopsy. The background diabetic retinopathy was seen in 47% of patients with TIN without clinical evidence of diabetic nephropathy. The recovery of renal function or clinical improvement was observed in 47% of patients with NDRD with institution of appropriate treatment. CONCLUSION: The prevalence of NDRD was 12.3% in our type 2 diabetic patients. Both non-diabetic glomerulopathy (47%) and tubulo-interstitial nephropathy (53%) can occur with nearly equal frequency in such patients. It is also gratifying to diagnose and treat NDRD in type 2 diabetics in selected cases. PMID- 11762611 TI - Dapsone in treatment of chronic idiopathic thrombocytopenic purpura in adults. AB - BACKGROUND: When a patient is steroid-dependant, a currently available strategy in chronic idiopathic thrombocytopenic purpura (ITP) is to follow a trial and error approach with any of the known drugs which has been found effective in the condition. OBJECTIVE: To evaluate the response of chronic ITP to dapsone, an inexpensive drug now reported to be effective in the disease. DESIGN: A controlled trial of abstinence and rechallenge type. SUBJECTS: Eight subjects with chronic ITP. INTERVENTIONS: Phase I - Intake of 100 mg of dapsone daily until response (in form of rise of platelet count in blood), Phase II - Above followed by drug abstinence, minimum for four weeks, and then rechallenge with the drug. MAIN OUTCOME MEASURES: Platelet counts during various phases viz during drug intake, withdrawal and rechallenge. RESULTS: Four (50%) patients responded to treatment. The mean pre-dapsone and post-dapsone platelet counts of blood were 29.6 x 10(9)/l and 142.5 x 10(9)/l respectively during the first phase of trial. The rechallenge was done in five patients following withdrawal of drug and the mean values of platelet count before and after rechallenge were 32.2 x 10(9)/l and 83 x 10(9)/l respectively. There was a remarkable response in two patients; one is now off the drug and the other on a maintenance dose of 50 mg of dapsone daily. CONCLUSION: Dapsone caused significant rise of platelet count in some patients of chronic ITP. It can be tried as an alternative to other second-line drugs in chronic ITP. PMID- 11762612 TI - Effect of intravenous quinine on capillary glucose levels in malaria. AB - OBJECTIVE: Hypoglycemia occurring during management in patients of severe malaria is often overlooked, which can be associated with higher morbidity and mortality rates. METHOD: Capillary glucose was estimated in 32 patients of malaria before, at one hour and at six hours of quinine administration. Quinine was given in saline solution intravenously. RESULTS: Pretreatment capillary glucose was found to be lower (71-80 mg/dl) in 12.5% cases. After one hour of intravenous quinine administration, capillary glucose levels fell by 11.84% in all the cases. A further fall of 20.50% was observed in 75% of cases after six hour. Two patients died and both were suffering from cerebral malaria. Statistically, fall in capillary glucose was highly significant at one hour (t=9.4, p < 0.001) and at six hours. (t=3.87, p < 0.001) CONCLUSION: Statistically significant fall in capillary glucose levels has been observed in patients of malaria with quinine administration. PMID- 11762613 TI - Clinical, hematological and histomorphological profile of myelodysplastic syndrome. AB - AIM: The present study was designed to analyse clinical, haematological and histomorphogical features in 37 cases of myelodysplasic syndrome (MDS). MATERIAL AND METHODS: FAB criteria was used to diagnose MDS in 37 patients. Clinical details, peripheral blood findings, bone marrow aspirate and biopsy were reviewed. RESULTS: Of 37 cases, there were 25 females and 12 males in age range of 2 years to 75 years. There were three children. There were nine cases of refractory anaemia (RA), 18 of refractory anaemia with excess blasts (RAEB), nine of refractory anaemia with excess blasts in transformation (RAEB-t) and one of chronic myelomonocytic leukemia (CMML). All were denovo MDS. All patients had pallor. Hepato and/or splenomegaly was seen in 15 cases. Anemia, leukopenia and thrombocytopenia was seen in 37, 6 and 23 cases respectively. Bone marrow aspiration (BMA) was hyper to normo cellular in 35 cases. Dyshemopoiesis was seen in one or more cell lines in all cases. Bone marrow biopsy (BMB) was available in 16 cases. Abnormal localisation of immature precursors (ALIP) was seen in 11/12 biopsies of RAEB and 3/4 of RAEB-t. BMB was helpful in diagnosis of 3 doubtful cases (one RAEB and two RAEB-t), and upgrading of 2 cases of RAEB to RAEB-t. On follow up, 1 case of RA, 3 of RAEB, 1 of RAEB-t developed AML. One case of RAEB developed ALL and 2 progressed to RAEB-t. CONCLUSION: Primary MDS is seen in all age groups. Pallor is commonest presentation. RAEB was commonest subgroup seen. BMB is helpful in diagnosis of doubtful cases. ALIP is a reliable diagnostic feature of MDS. BMB is a diagnostic as well as prognostic tool in MDS cases which should be taken as a mandatory investigation. PMID- 11762614 TI - Clinical profile of AIDS. AB - OBJECTIVES: To study clinical presentation, spectrum of systemic involvement and opportunistic infections in AIDS patients. METHODS: Thirty patient HIV positive by ELISA test, admitted in the department of Medicine SMS Hospital, Jaipur during September, 1996 and December, 1997, were studied. Other causes of immunosuppression were ruled out. These patients having opportunistic infections and/or systemic involvement were diagnosed to have AIDS and per CDC Atlanta criteria. The patients and their spouses were interviewed, examined and investigated according to the pre-designed proforma. RESULTS: Twenty five male and five female patients (n=30), having mean age of 32.76+/-8.14 years (range 23 55 years) were studied. Ninety percent were in 20-40 years age group. Forty percent were related to transport services, while 43% had migrated to other areas. Sexual mode of transmission was seen in 21 subjects (70%) (20 males and one female), of which 18 were heterosexual and three bisexual. Four patients (13%) had history of blood transfusion. The commonest presentation was fever in ninety six per cent. Significant weight loss (1.5%+/-9.76%) was present in patients having associated Candida infection (n=15). Tubercular disease was seen in 66% and 30% had atypical presentations. A presumptive diagnosis of PCP was made in 10% while 30% had cryptococcal infection. The most common system involved was GIT (70%). All the patients were tested HBsAg negative. AIDS dementia complex was diagnosed in 13% all aged above 35 years. CONCLUSION: Occupation and migration were important risk factors for HIV transmission and heterosexual contact is the commonest mode of spread. Amongst infection, tuberculosis and candidiasis were common. PMID- 11762615 TI - Diabetic retinopathy and microalbuminuria in lean type 2 diabetes mellitus. AB - BACKGROUND: Relationship between microalbuminuria and diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus has been described. Patients with lean type 2 diabetes mellitus has some difference of insulin secretion and action in comparison with obese type 2 diabetes mellitus and there are evidences to support that lean type 2 diabetes mellitus is slow emerging type 1 diabetes mellitus in our population. The aim of this study is to find out correlation between retinopathy and microalbuminuria in lean type 2 diabetes mellitus. METHODS: Fifty two patients with lean type 2 diabetes mellitus (BMI < 18.5 Kg/M2) were selected. Diabetic retinopathy was observed in 25 patients only. Blood glucose sample was taken after 10 hours of overnight fasting. Glycosylated haemoglobin (HbA1c) was measured by calorimetric method and urinary albumin was estimated in morning urine saniple by Micral II test strip. RESULTS: Patients with diabetic retinopathy had longer duration of diabetes detected than those with normal fundus but the difference was statistically insignificant. Fasting blood glucose greater than 200 mg/dl was found in 63.6% of patients with diabetic retinopathy and in 36.4% of patients with normal fundus but the difference was insiginificant. Patients with diabetic retinopathy had microalbuminuria test positive and level was significantly higher in patients with proliferative retinopathy than in patients with background retinopathy. CONCLUSION: Microalbuminuria is associated with diabetic retinopathy in lean type 2 diabetes mellitus. Increase in urinary albumin excretion correlates with development of proliferative diabetic retinopathy in lean type 2 diabetes mellitus similar to type 1 and type 2 diabetes niellitus. This study emphasizes that microalbuminuria estimated by semi quantitative method is a cost effective and reliable marker of diabetic retinopathy in lean type 2 diabetes mellitus and high level of this may serve as an indicator of proliferative retinopathy in them. PMID- 11762616 TI - Age-related proximal femur bone mineral loss in South Indian women: a dual energy X-ray absorptiometry study. AB - OBJECTIVES: i) To collect normative data for proximal femur bone mineral density (BMD) in South Indian women using dual energy X-ray absorptiometry (DXA) and ii) to study the rate and significance of hip bone mineral loss with advancing age in this population. MATERIAL AND METHODS: Forty five women, whose age ranged from 16 to 84 years were studied. This sample was drawn randomly from general medical practice at KJ Hospital, Chennai, South India during November, 1997 to April, 1998. Of these 45 cases, 21 were pre-menopausal (mean +/- SD age = 30.9+/-8.8 years) and 24 post-menopausal (mean +/- SD age = 62.1+/-11.0 years). Subjects with secondary bone diseases were excluded. Also excluded were those taking any drugs known to affect calcium metabolism e.g., thiazide diuretics, oestrogen and calcium. Subjects were divided into seven decadal age groups from 15-24 years to 75-84 years. BMD of the right proximal femur was evaluated using a QDR-1000 DXA bone densitometer (Hologic Inc., Waltham, Massachusetts, USA). Data analysis was done with SPSS/PC statistical software package. RESULTS: Linear regression analysis showed significant (p < 0.001) negative correlations between all hip BMD variables at different regions of interest and patient's age. Relative to that at 30 years of age, rates of BMD loss in the neck of femur, trochanter, intertrochanter, total hip and Ward's triangle were 0.68%, 0.65%, 0.58%, 0.61% and 1.05% per annum respectively. Over the age of 65 years, the above mentioned regions BMD decreased by 0.91%, 0.84%, 0.72%, 0.78% and 1.66% per annum respectively. CONCLUSION: Normative data for proximal femur BMD in South India women have been evaluated and it may prove useful for diagnosing osteoporosis in the women of South India. PMID- 11762617 TI - Pictorial CME. Osteogenesis imperfecta. PMID- 11762618 TI - Systemic (adjuvant) treatment of primary breast cancer. AB - Breast cancer is a disease with long natural history. The pattern of practice should be expected to change. With the current speed of research, we should expect many changes in many aspects of treatment in next millennium. PMID- 11762619 TI - Role of anaesthetic equipment in transmitting nosocomial infection. AB - There is a potential risk of bacterial and viral infection being transmitted through anaesthesia circuits. Several studies have shown contamination of parts of anaesthetic equipment with bacteria that colonise the mouth and upper airway. A definite relationship between such contaminated anaesthetic equipment and subsequent lung infection remains to be established. Various factors contribute to the transmission and pathogenesis. Among the recommendations for preventing transmission of infection through anaesthetic circuits are using a bacterial/viral filter for every patient or using disposable circuits. Owing to financial constraints, all these recommendations may not be practical in India. Possible guidelines for India may include discarding endotracheal tubes after single use and rigorous cleaning and disinfection of masks and laryngoscopes. Corrugated tubings used in the expiratory limb of the circuit may be washed with soap and water after each patient and dried before use. It is advisable to disinfect all such tubings in 2% glutaraldehyde, and then to wash in water and to dry before use at least once a day or when they are visibly contaminated. PMID- 11762620 TI - Efficacy and cost effectiveness of current therapies in Guillain Barre syndrome. PMID- 11762621 TI - Intercostal lung herniation--depiction on spiral CT. AB - Computed tomography (CT) is the imaging modality of choice for the demonstration of intercostal lung herniation. The use of forced expiration and Valsalva's manouevre during CT scanning has been recommended in selected cases. We report a case of intercostal lung herniation, demonstrated only on coughing on spiral CT. PMID- 11762622 TI - Essential thrombocythemia--a cause of myocardial infarction in a young male. PMID- 11762623 TI - Bilateral renal angiomyolipomas in association with end stage renal disease without features of tuberous sclerosis. AB - We report a case of end stage renal disease in association with bilateral renal angiomyolipomas (RAML). There were no features suggestive of tubercous sclerosis (TS). Renal angiomyolipomas were detected incidentally, patient being asymptomatic for the same. She is being evaluated for live related kidney transplant. PMID- 11762624 TI - An unusual paratyphoid fever. AB - Salmonella typhi is known to produce acalculous cholecystitis and related gall bladder perforation. Following is a documentation of a patient of sub-phrenic abscess and gall bladder perforation which was possibly a result of Salmonella paratyphi A. PMID- 11762625 TI - Metastatic sweat gland carcinoma. AB - Sweat gland tumours are very rare. They lack distinctive clinical features and the histological appearences are often varied. Hence, diagnosis is difficult and usually late. We report a case of sweat gland adenocarcinoma with bony and lymphnode metastases, and possibly secondary involvement of 7th cranial nerve. This is probably the first case in Indian literature. PMID- 11762626 TI - 46 3q+ karyotype presenting as syndrome with obesity and hypogonadism. PMID- 11762627 TI - Paroxysmal nocturnal haemoglobinuria presenting as recurrent episodes of cerebral venous thrombosis. PMID- 11762628 TI - Vocal cord dysfunction presenting as recurrent acute severe asthma. PMID- 11762629 TI - Neuroblastoma in an adolescent girl. PMID- 11762630 TI - Salmonella typhi in injection abscess. PMID- 11762631 TI - Antiplatelet effect of aspirin--need for further research. PMID- 11762632 TI - Face of God. PMID- 11762633 TI - Anomalous origins of right coronary and left anterior descending coronary arteries: angiographic profiles. PMID- 11762634 TI - Elections and nail growth--a new physical sign? PMID- 11762635 TI - Neuroleptic malignant syndrome. PMID- 11762636 TI - Study of diabetic hand syndrome (DHS) in Indian NIDDM patients. PMID- 11762637 TI - Cisapride--a word of caution. PMID- 11762638 TI - Single small enhancing lesions and SPECT. PMID- 11762639 TI - An unusual clinical presentation of cobalamine deficiency. PMID- 11762640 TI - A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity. AB - Earlier we reported potent cRaf1 kinase inhibitors with a key acidic phenol pharmacophore that had, at best, adequate cellular efficacy. To improve the cellular potency, phenol isosteres and prodrugs were investigated. Many phenol isosteres were synthesized and tested, but failed to provide adequate enzyme potency. A prodrug approach resulted in a 2- to 17-fold improvement over the parent compound in cell-based efficacy. PMID- 11762641 TI - Cancerostatic octadecylpiperidinoylphosphate liposomes: effect of composition on uptake by and toxicity to J774 mouse macrophage cells and MT1 breast cancer cells in vitro. AB - Liposomes prepared from the cancerostatic octadecyl-(N,N-dimethylpiperidino-4-yl) phosphate (OPP) were investigated in order to characterize the influence of composition on cytotoxicity and to minimize side effects on the immune system. Differently composed liposomes with respect to charge, cholesterol content and steric stabilization were used. Fluorescence measurements and the MTT assay were applied to investigate the effect of uptake and cytotoxicity, respectively, on J774 mouse macrophages and MT1 human breast cancer cells in vitro. Because of their endocytotic capability, uptake was generally higher for macrophages compared with tumour cells. OPP liposomes, which are negatively charged, cholesterol-poor and sterically stabilized, showed the lowest total and internal uptake by both cell lines. On the other hand, these liposomes were also the most cytotoxic ones for both cell lines investigated, with an inhibitory concentration of between 50 and 80 microM. Cytotoxicity does not correlate with cellular uptake and is most likely caused by other mechanisms. The results demonstrate that cancerostatic liposomes have composition-dependent toxic effects on macrophages which have to be seriously considered. For therapeutic experiments in vivo liposomes should be negatively charged and sterically stabilized and composed of OPP and cholesterol in a molar ratio of approximately 1. PMID- 11762642 TI - A novel B-ring modified homocamptothecin, 12-Cl-hCPT, showing antiproliferative and topoisomerase I inhibitory activities superior to SN-38. AB - We report the synthesis and pharmacological evaluation of a novel homocamptothecin (hCPT) derivative, 12-Cl-hCPT, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha hydroxylactone found in camptothecin (CPT) and bears a chloro substituent at position 12. The capacity of 12-Cl-hCPT to inhibit DNA topoisomerase I was compared with that of SN-38, the active metabolite of the clinically used antitumour prodrug CPT-11. In the DNA relaxation assay, 12-Cl-hCPT proved to be slightly more potent than SN-38 at stimulating the formation of nicked plasmid DNA molecules. A series of radiolabelled DNA restriction fragments were employed to identify and compare the position of the DNA cleavage sites induced by topoisomerase I in the presence of 12-Cl-hCPT and SN-38. These sequencing studies confirm that both 12-Cl-hCPT and SN-38 strongly promote DNA cleavage by topoisomerase I and reveal that the majority of the cleavage sites are located at the same nucleotide positions for the two drugs. However, a certain number of DNA cleavage sites were found to be specific to 12-Cl-hCPT. These sites, previously characterized with unsubstituted hCPT, generally correspond to 5'-CG sites whereas the sites common to the 12-Cl-hCPT and SN-38 essentially correspond to 5' TG sites. We also quantified the formation of drug-induced protein-DNA complexes formed in HT29 human colon carcinoma cells. Trapping of endogenous proteins onto DNA was found to be much more efficient with 12-Cl-hCPT than with SN-38. These data provide a molecular basis to account for the enhanced antiproliferative activity of 12-Cl-hCPT compared with that of SN-38. Biological evaluation on a panel of sensitive and drug-resistant cell lines revealed 12-Cl-hCPT to be more cytotoxic to tumour cells than SN-38. 12-Cl-hCPT proved 14- and 23-fold more active than SN-38 toward the K562adr and T24anp multidrug-resistant cell lines, respectively. The marked topoisomerase I inhibitory properties of 12-Cl-hCPT coupled with its interesting antiproliferative activity, in particular against cancer cells presenting multidrug resistance phenotype with overexpression of P glycoprotein, makes 12-Cl-hCPT a valid candidate for subsequent preclinical evaluation. Collectively, the data strengthen homocamptothecin as an extremely promising template to generate novel and potent antitumour agents. PMID- 11762643 TI - Synthesis, evaluation and QSAR studies of highly potent aromatase inhibitors of the piperidinedione type. AB - The syntheses of new cycloalkyl- and cycloalkylalkyl-substituted 3-(4 aminophenyl)-piperidine-2,6-diones and their evaluation as aromatase inhibitors is described. Seven of the new compounds were more active in vitro than the cyclohexyl compound (CHAG), a former clinical candidate: cycloheptyl (1), cycloheptylmethyl (2), cyclohexylmethyl (3), cyclopentylmethyl (4), 1 adamantylmethyl (6), 2-cyclohexylethyl (7) and 2-cyclopentylethyl (8). Compound 3 was the most active, exceeding the potency of aminoglutethimide (AG) and CHAG by factors of 356 and 3, respectively, and reaching the activity of fadrozole. With the exception of 4, the other highly potent aromatase inhibitors were less active towards P450 scc compared with AG. Selected compounds showed only little inhibition of P450 18. In a QSAR study including analogous non-cyclic alkyl substituted piperidinediones a linear relationship between logP and -logIC50 was found. Tested in vivo, compounds 1, 3, 4, 6 and 7 inhibited androgen-stimulated uterine growth in immature Sprague-Dawley rats as potently as CHAG. At a dose of 8.6 micromol/kg body wt compound 2 was superior to CHAG and thus might be a candidate for the treatment of breast cancer. PMID- 11762644 TI - Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S cysteaminylphenol substituted with two methyl groups alpha to the nitrogen. AB - N-Acetyl-4-S-cysteaminylphenol 1 is an analogue of a biosynthetic intermediate in the pathway to melanin. It is probably oxidized to an o-quinone which can alkylate cellular nucleophiles resulting in interference with cell growth and proliferation. It is reported to have useful anti-melanoma activity. We previously synthesized a range of analogues of 1 by varying the acyl portion of the amide. A modest increase in melanoma activity against six melanoma cell lines for these analogues could be correlated with increased lipophilicity. Thirteen new analogues of 1 containing two methyl groups at the alpha-position of the amino component and various acyl groups have now been prepared and assessed for anti-melanoma activity against six human melanoma cell lines. Most of the new compounds displayed greater cytotoxicity than the lead compound 1. The highest cytotoxicity against the cell lines was observed for the cyclohexylacetamide 11 followed by the cyclohexylcarboxamide 10 and the 2,2-dimethylpropanamide 6. The IC50 values of the most cytotoxic compound 11 against the cell lines were comparable with those of cisplatin. Small variations in the acyl components of these analogues, such as reducing the ring size, lengthening the carbon chain and reducing the amount of chain branching, resulted in a considerable loss of cytotoxicity. The moderate activity of 6, 10 and 11 against SK-Mel-24 cells (non tyrosinase containing) and an ovarian cell line suggests that interference with the melanin pathway may not be their only mode of action. PMID- 11762645 TI - Ethyl side-chain modifications in novel flexible antiestrogens--design, synthesis and biological efficacy in assay against the MCF-7 breast tumor cell line. AB - To examine the efficacy of ethyl side-chain modifications in a family of flexible non-steroidal modulators of the estrogen receptor, a series of novel compounds was prepared and their antiproliferative effects on human MCF-7 breast tumor cells evaluated. These flexible antiestrogens consisted of members wherein the ethyl portion of the parent compound, a flexible analogue of tamoxifen, had been modified so as to introduce halogens or a nitro group, or to extend the side chain length from ethyl to propyl or butyl. The compounds demonstrated potency at low micromolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low associated cytotoxicity. Tested compounds exhibited nanomolar binding affinity (Ki) for the estrogen receptor (ER) as determined through displacement of radiolabelled estradiol. Semiempirical calculations predict an inherent lower oxidative potential at the allylic position, similar to that calculated for the established analogue toremifene, indicating a lesser propensity of such compounds towards metabolic oxidative carbocation generation and consequent DNA adduct formation. Computational studies predict these compounds to bind in a typical estrogen antagonist mode within the ER-ligand binding domain (LBD). Ethyl side-chain modification in this compound class is well tolerated within the ER and is not detrimental to compound efficacy, with additional potential anti-carcinogenic properties imbued to the molecule. PMID- 11762646 TI - Cell-based screening approach for antitumor drug leads which exploits sensitivity differences between normal and cancer cells: identification of two novel cell cycle inhibitors. AB - A cell-based in vitro screening approach for identification of antitumor drug leads that exploits the differential sensitivity between normal and cancer cells was developed. It is a three-step, high-throughput screen for antiproliferative and/or cytotoxic activity measured by a 7 day MTT [3-(4,5-dimethylthiazol-2yl) 2,5-diphenyl tetrazolium bromidel assay using small panels of proliferating primary human cells and established cancer cell lines. Proof-of-concept experiments successfully identified 11 known cancer drugs randomly mixed with 5000 test compounds. Application of this screening approach to a library of 110000 compounds allowed for the identification of several novel chemical classes of compounds active against an expanded panel of cancer cell lines in vitro. Two of the compounds representing novel mitotic inhibitors with in vivo potency against established breast cancer xenografts (MDA-MB-435) are reported here. PMID- 11762647 TI - Does the fetus lose weight in utero following fetal death: a study in preterm infants. AB - OBJECTIVE: To evaluate whether the fetus loses weight in uttero following fetal death, looking specifically at weight differences according to whether the death occurred during labour or before labour. DESIGN: Record linkage of maternity data and perinatal mortality data. SETTING: Scotland, UK. Population A group of 8,069 singleton live and stillbirths without obvious congenital abnormalities delivered at 24-32 weeks. MAIN OUTCOME MEASURE: Birthweight. RESULTS: Stillborn infants weighed less than liveborns of equivalent gestational age at delivery. Stillborn infants in whom the death occurred during labour weighed more than those in whom the death occurred before labour; this applied to both vaginal deliveries and those by caesarean section. CONCLUSIONS: These findings could be attributed to the hypothesis that the low birthweight of stillborn infants is due to weight loss following the death, in addition to any process of growth restriction before the death. The analysis described here contains no data which would negate this hypothesis. PMID- 11762648 TI - Seasonal variation in the occurrence of pre-eclampsia. AB - OBJECTIVE: To obtain evidence for seasonal variability in pre-eclampsia using the assumption that environmental factors may have a role in the causal mechanisms. DESIGN: Cross sectional population-based study. POPULATION: All 1,869,388 deliveries in Norway in the years 1967 to 1998. METHOD: For each month, the percentage of births complicated by pre-eclampsia was calculated. The relative risks of pre-eclampsia by month of delivery were estimated as odds ratios using the month with lowest risk as the reference category. RESULTS: Mothers of children born in August had the lowest risk of pre-eclampsia, and the risk was highest in the winter months (for December adjusted OR: 1.26, 95% CI 1.20-1.31). This pattern was independent of parity. maternal age, year and place of living. CONCLUSION: The finding may provide a new clue for understanding the causes of pre-eclampsia. Environmental factors that show a similar seasonal variation should be investigated as possible causes. PMID- 11762649 TI - The relationship between cervical dilatation at initial presentation in labour and subsequent intervention. AB - OBJECTIVE: To examine the relationship between the cervical dilatation at which women present in labour and the subsequent likelihood of caesarean section. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. POPULATION: 3,220 women met the entry criteria from 14,050 deliveries between January 1995 and December 1999. METHODS: Women meeting the following criteria were identified: those in spontaneous labour with a singleton pregnancy and a cephalic presentation at 37-42 weeks of gestation; all women delivering within 36 hours of first presentation were included. Women who had spontaneous rupture of the membranes before first attendance were excluded. MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section. Secondary outcomes were operative vaginal delivery, fetal weight, cord pH, five minute Apgar score, length of labour, labour augmentation with oxytocin and epidural analgesia. RESULTS: The risk of caesarean section decreased with increasing cervical dilatation at presentation. This was true for nulliparous (n = 1,168) and parous women (n = 2,052). The caesarean section rate of nulliparous women presenting at 0-3cm (n = 812) was 10.3%, compared with 4.2% for those presenting at 4cm-10 cm (n = 356), and the mean duration of labour before presentation was 2.0 hours versus 4.5 hours, respectively (P = 0.0001). For parous women the caesarean section rates were 5.7% and 1.3%, respectively (P = 0.0001). There were significantly greater frequencies of use of oxytocin and epidural analgesia by women presenting earlier in labour. The caesarean section rate of 185 nulliparae (15.8%) who were initially allowed home was no different from those admitted immediately (9.2% vs 8.2%, P = 0.67). Similarly, 196 (9.5%) of multiparae went home and had a caesarean section rate of 3.6%, compared with 3.1% if admitted immediately (P = 0.76). CONCLUSIONS: Women who present to hospital at 0-3cm spend less time in labour before presentation and are more likely to have obstetric intervention than those presenting in more advanced labour. Outcomes were similar whether or not the woman was initially allowed home. PMID- 11762650 TI - The association between maternal HIV-1 infection and pregnancy outcomes in Dar es Salaam, Tanzania. AB - OBJECTIVE: To examine the association between maternal HIV infection and pregnancy outcomes controlling for potential confounding factors among a cohort of HIV-uninfected and HIV-infected pregnant women in Dar es Salaam, Tanzania. DESIGN: Prospective cohort study. METHODS: A cohort of 1,078 HIV-infected and 502 HIV-uninfected pregnant women between 12 and 27 weeks of gestation were enrolled and followed up until delivery. Multiple regression models were used to compare the risk of adverse pregnancy outcomes among HIV-uninfected women with those among HIV-infected women overall, and separately among asymptomatic or symptomatic HIV-infected women. RESULTS: No significant differences between HIV uninfected women and HIV-infected women were observed in risks of fetal loss or low birthweight or in the weight, head circumference and gestational age of infants at birth. HIV-infected women were more likely to have severe immature infants (<34 weeks) than HIV-uninfected women (multivariate RR 1.54 [95% CI 0.90 2.48]; P= 0.05). There was a significantly higher risk of low birthweight (RR 2.29, 95% CI 1.34-3.92; P = 0.03) and prematurity (<37 weeks) (RR 1.93, 95% CI 1.35-2.77; P = 0.0003) among symptomatic HIV-infected women when compared with HIV-uninfected women. CONCLUSION: HIV-infected women, particularly those whoare symptomatic, are at a higher risk of adverse pregnancy outcomes. PMID- 11762652 TI - Pregnant women with chronic hypertension and superimposed pre-eclampsia have high cerebral perfusion pressure. AB - OBJECTIVE: To determine any differences in cerebral perfusion pressure in patients with chronic hypertension compared with those with chronic hypertension and superimposed pre-eclampsia. DESIGN: A prospective observational study. SETTING: University hospital clinic and labour and delivery suite. PARTICIPANTS: Fifteen women with chronic hypertension and 15 with superimposed pre-eclampsia. METHODS: Transcranial Doppler ultrasound was used to measure blood velocity in the middle cerebral arteries of the patients. Systemic blood pressure in the brachial artery was measured simultaneously. Middle cerebral artery. resistance index, pulsatility index, and cerebral perfusion pressure were calculated and plotted on the same axes as data from normal pregnant women. Cerebral perfusion pressure values outside of the 5th and 95th centiles were regarded as abnormal. Cerebral perfusion pressure data from the chronic hypertension and superimposed pre-eclampsia groups were also expressed in terms of the number of normative standard deviations from the mean value for normal pregnancy (Multiples of the Standard Deviation: MOS). All studies were conducted before labour, under similar conditions, and before volume expansion or treatment. Statistical analysis was by Student's t test and Fisher's exact test as appropriate with significance set at a two-tailed P<0.05. RESULTS: Patient demographics and blood pressure were not significantly different between the two groups. The resistance index and pulsatility index were not significantly different (neither absolute nor multiples of the standard deviation values). The absolute cerebral perfusion pressure was significantly higher in the patients with superimposed pre eclampsia. The group of women with superimposed pre-eclampsia had a significantly higher mean value of cerebral perfusion pressure measured as multiples of the standard deviation from the mean value for normal pregnancy, despite there being no blood pressure difference. CONCLUSIONS: Superimposed pre-eclampsia is associated with significantly higher cerebral perfusion pressure measurements compared with women with uncomplicated chronic hypertension. This is not directly related to a higher blood pressure. The difference in cerebral perfusion pressure may be used to speculate upon the pathophysiology of the increased risk for eclampsia seen in patients with superimposed pre-eclampsia. PMID- 11762651 TI - Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. AB - OBJECTIVE: To assess the maternal, fetal and neonatal safety of enoxaparin in pregnant women who require antithrombotic therapy. DESIGN: Retrospective analysis of case notes of women who received enoxaparin during pregnancy, irrespective of dose, duration and reason for treatment. SETTING: Fifty-five French perinatal centres. SAMPLE: Data from 624 pregnancies in 604 women between 1988 and 1997. The incidence of previous thromboembolism was 29.8%, known thrombophilia 15.2%. METHODS: Indication, regimen of enoxaparin and outcome measures were reported for each pregnancy. Information was obtained from case records, validated by research staff and analysed by an independent scientific committee. MAIN OUTCOME MEASURES: Incidence, seriousness and causality of maternal, fetal and neonatal adverse events, pregnancy outcome, and incidence of venous thromboembolism. RESULTS: Enoxaparin was administered for treatment of an acute episode in 49 cases and for thromboprophylaxis in 574 cases. Serious maternal haemorrhage occurred in 11 cases during pregnancy (1.8%), one being reasonably related to enoxaparin, and in nine cases at delivery (1.4%), all unrelated to enoxaparin. Maternal thrombocytopenia was reported in 10 cases (1.6%). two being serious but unrelated to enoxaparin. Eight pregnancies ended in stillbirth (1.1%). Among the 693 live births, 17 major congenital abnormalities (2.5%) and 10 serious neonatal haemorrhages (1.4%) were reported. None of the fetal or neonatal adverse events was related to enoxaparin. Eight venous thromboembolic events (1.3%) were reported. CONCLUSIONS: The incidence of adverse events reported could be explained by the high risk profile of the study population. Overall, this retrospective study suggests enoxaparin is well tolerated during pregnancy. PMID- 11762653 TI - Impaired vascular function in women with pre-eclampsia observed with orthogonal polarisation spectral imaging. AB - OBJECTIVE: To investigate in vivo the function of the microcirculation of the skin in pregnancy and pregnancy complicated with pre-eclampsia. DESIGN: Case control study. SETTING: Academic Medical Centre. PARTICIPANTS: A group of 10 women with pre-eclampsia and a healthy control group of 10 pregnant women. METHODS: The microcirculation of the skin of the finger at rest and during venous occlusion was studied with laser Doppler fluxmetry and orthogonal polarisation spectral imaging. By inflating a cuff around the upper arm to a pressure of 50 mmHg, causing venous occlusion, the local sympathetic veno-arteriolar reflex was provoked. With laser Doppler fluxmetry the blood flow of the skin at a depth of 1 2mm was measured at rest and during venous occlusion. Orthogonal polarisation spectral imaging was used to assess red blood cell velocity at rest and during venous occlusion of the nutritive capillaries of the skin. RESULTS: Laser Doppler fluxmetry showed no significant difference between the normotensive group and the group with pre-eclampsia. Using orthogonal polarisation spectral imaging, venous occlusion produced a significantly greater decrease in red blood cell velocity in the control group than in the women with pre-eclampsia: (84% (81-88)(median and interquartile range) vs 58% (45-88), P = 0.0029). No differences in absolute red blood cell velocities were observed between groups either at rest or during venous occlusion. CONCLUSION: This study shows an impaired local veno-arteriolar reflex in pre-eclampsia at the nutritive, but not at the therrmoregulatory, level of the microcirculation of the skin. PMID- 11762654 TI - Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities. AB - OBJECTIVE: To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha fetoprotein (% alpha-fetoprotein-L2 + L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. DESIGN: Prospective consecutive series. SETTING: University hospital. SAMPLE: Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. RESULTS: The proportion of alpha-fetoprotein-L2 + L3 in maternal serum for trisomy 21 (40.3%. P < 0.0001) and trisomy 18 (39.8%, P < 0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2 + L3 in amniotic fluid was significantly higher (P < 0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2 + L3 between maternal serum and amniotic fluid (r = 0.840, P < 0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2 + L3 in maternal serum and amniotic fluid. CONCLUSION: The proportion of alpha-fetoprotein-L2 + L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2 + L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening. PMID- 11762655 TI - A comparison of fetal behaviour in term fetuses exposed to anticonvulsant medication with unexposed controls. AB - OBJECTIVE: To compare behaviour in term fetuses exposed to anticonvulsants with unexposed controls. DESIGN: An observational study. SETTING: Pregnancy Assessment Centre, University Hospital, Nottingham, UK. SAMPLE: Seventeen fetuses whose mothers were taking anticonvulsants and 94 fetuses whose mothers were on no medication between 28 and 41 weeks. METHODS: Behaviour (fetal heart rate and activity) was recorded with the use of Doppler ultrasound. The duration of recording was 60 minutes or more in all but four recordings (minimum 49 minutes). MAIN OUTCOME MEASURES: Behavioural criteria studied were: 1. the relative percentage time spent in low and high variation fetal heart rate patterns; 2. the duration and recurrence of fetal activity; 3. the number of accelerations in low and high fetal heart rate variation; and 4. the number of fetal behavioural state transitions. RESULTS: The two groups were comparable in terms of maternal age, parity. birthweight, Apgar scores and absence of neonatal problems. There was less fetal activity in the anticonvulsant group, but this was only statistically significant at 33-36 weeks in fetal heart rate pattern B (equivalent to state 2F). CONCLUSIONS: This study showed that fetuses exposed to anticonvulsant medication exhibited a trend of being less active. There were no other significant differences in behaviour. The data do not support the hypothesis of substantial differences in behaviour in fetuses exposed to anticonvulsants. PMID- 11762656 TI - Pregnancy and the erythrocyte sedimentation rate. AB - OBJECTIVES: To determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women. To examine the effect of gestational age and haemoglobin concentration on erythrocyte sedimentation rate. SETTING: Queen Charlotte's Hospital, London, UK. DESIGN: Cross sectional descriptive study. Population Healthy pregnant women attending for routine outpatient antenatal visits at Queen Charlotte's Hospital in London. METHODS: Erythrocyte sedimentation rate was determined by the Westergren method, haemoglobin concentration by automated cell counter and gestational age by ultrasonography. The median and 95% reference range was determined for erythrocyte sedimentation rate values obtained. Linear regression analysis was used to determine the influence of haemoglobin concentration and gestational age on erythrocyte sedimentation rate. RESULTS: For 1,019 women examined, the range of erythrocyte sedimentation rate values obtained was 4-112 mm/ h. Gestational age and haemoglobin concentration both significantly influenced erythrocyte sedimentation rate. (P < 0.0001). For non-anaemic women the 95% reference range rose from 18-48 mm/h in the first half of pregnancy to 30-70 mm/h in the second half of pregnancy. For anaemic women the corresponding reference ranges were 21-62 mm/h and 40-95 mm/h, respectively. CONCLUSION: For the correct interpretation of erythrocyte sedimentation rate values obtained during pregnancy gestational age and haemoglobin concentration must be taken into account. PMID- 11762657 TI - Insertion of an intrauterine contraceptive device after induced or spontaneous abortion: a review of the evidence. AB - OBJECTIVE: Assess the safety and efficacy of intrauterine contraceptive device (IUCD) insertion immediately after induced or spontaneous abortion. DESIGN: Systematic search for randomised trials that had at least one treatment arm that involved IUCD insertion immediately after an induced or spontaneous miscarriage using Medline, Popline, EMBASE, and review articles supplemented by correspondence with investigators. POPULATION: Women of any age or gravidity who had an IUCD inserted immediately after evacuation for spontaneous or induced abortion. METHODS: Articles were abstracted and the raw data from tables were analysed with RevMan 3.1 software. We focused on Tietze-Potter gross life table probabilities with denominators of person-time of exposure. MAIN OUTCOME MEASURES: Rates of perforation, expulsion, pelvic inflammatory disease, contraceptive failure, and method continuation. RESULTS: Complication rates for immediate post-abortal IUCD insertion were low. Perforation was rare with a rate of approximately one per 1,000 insertions. One year gross cumulative expulsion rates ranged from 1.8% to 12.6%, pregnancy rates from 0.6% to 2.1%, and continuation rates from 54% to 90%. The net discontinuation rate due to pelvic inflammatory disease was low, ranging from 0.0 to 0.8 per 100 women at one year. Increasing gestational age at insertion was associated with increased expulsion rates. CONCLUSIONS: Post-abortal IUCD insertion is safe and effective. The risks of perforation, expulsion, pelvic inflammatory disease and contraceptive failure were low and similar to those reported for interval insertion. Second trimester gestational age is associated with an increased risk of expulsion. Immediate insertion may have a higher expulsion rate than delayed insertion. However, these risks may be outweighed by the benefit of immediate contraception. PMID- 11762658 TI - Comparative study of the effects of a progestogen-only pill containing desogestrel and an intrauterine contraceptive device in lactating women. AB - OBJECTIVE: To evaluate the effects of desogestrel 75 microg/day, as a progestogen only pill compared with a copper-bearing intrauterine contraceptive device (IUCD) on lactation and to study the safety of both treatments in mothers and children. Transfer of etonogestrel to breast milk was studied in a subgroup of desogestrel users. The children were to be followed up until 2.5 years of age. DESIGN: An open, non-randomised, group-comparative study in lactating women. SETTING: University Hospital, Reykjavik, Iceland. PARTICIPANTS: A total of 83 lactating women; 42 received desogestrel and 41 had an IUCD inserted for seven consecutive treatment cycles of 28 days. METHODS: Evaluation visits were planned at baseline and at the end of treatment cycles 1, 4 and 7. The amount of breast milk was determined by weighing the infants before and after feeding, at baseline and after treatment cycles I and 4. Milk samples were obtained at the same time for constituent measurements. Safety was studied by structured medical examinations and by recording adverse experiences in mothers and children. RESULTS: There were no significant differences between the desogestrel and IUCD groups in composition and quantity of breast milk nor in growth and development of the children followed up to the age of 2.5 years. In the desogestrel group a slightly higher incidence of mild adverse experiences of a hormonal nature was reported among both mothers and infants. Of the children 82% were followed until 1.5 years of age and 50% until 2.5 years. CONCLUSION: The use of desogestrel 75 microg/day did not change the amount and composition of breast milk nor did it affect growth and development of the breastfed children. It appears to be a safe and effective contraceptive method for lactating women PMID- 11762659 TI - A randomised placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea. AB - OBJECTIVE: To determine whether vitamin E is effective in the treatment of primary dysmenorrhoea. DESIGN: A randomised placebo-controlled trial. PARTICIPANTS: One hundred girls, aged 16-18 years old who suffered from primary dysmenorrhoea, among 1,000 students attending a public high school in Region 5 in the Greater Tehran Municipality. METHODS: Fifty girls were given 500 units of vitamin E (five tablets) per day, and 50 were given five placebo tablets per day. The treatment began two days before the beginning of menstruation and continued through the first three days of bleeding. The severity of pain before and after the treatment was studied. Treatment in both groups was carried out in two consecutive menstrual periods. RESULTS: The severity of pain in the two groups was reduced after treatment, but the reduction was greater in the group treated with vitamin E. These differences were maintained in the second month of therapy. CONCLUSION: Both placebo and vitamin E are effective in relieving symptoms due to primary dysmenorrhoea, but the effects of vitamin E are more marked. PMID- 11762660 TI - Is conservative treatment for adenocarcinoma in situ of the cervix safe? AB - OBJECTIVE: To determine the long term results of treatment of adenocarcinoma in situ by conisation of the cervix using survival analysis. DESIGN: A retrospective study in six teaching hospitals in North West Thames. POPULATION: Eighty-five women with a histological diagnosis of adenocarcinoma in situ of the cervix in punch or cone biopsy were identified from pathology and clinical databases. RESULTS: In one patient a small focus of adenocarcinoma in situ was found in a cervical polyp. Subsequent cytology was normal and no further treatment was undertaken. The 84 remaining women underwent diathermy loop, cold knife cone biopsy, laser cone biopsy, or needle excision of the transformation zone. A hysterectomy or second conisation was performed in 31/84 women (36.9%) as part of the initial treatment. In all, nine (10.6%) had early invasive lesions of which four were squamous. Fifty-nine patients were treated conservatively following one or two conisations (median follow up 78 weeks, range 0-543 weeks). One had a subsequent hysterectomy for menorrhagia. Five women have undergone treatment for suspected recurrence, a 21.5% cumulative rate of further treatment by four years. The cumulative rate of histologically proven recurrence after conservative management was 4.3% at one year and 15% at four years. CONCLUSIONS: In those cases with clear margins in the cone biopsy, there is a place for conservative management of a selected group of patients who wish to preserve fertility. However, 16.7% of these will require further treatment after four years because of recurrent cytological abnormalities. Women who opt for conservative management should undergo regular, long term surveillance in a colposcopy clinic. Among those women with involved margins in the initial cone biopsy, there is a high incidence of residual disease. A second cone biopsy may be appropriate 'definitive treatment' for young women who wish to preserve their fertility if the margins of the second biopsy are clear and there is no evidence of invasion. Even among those for whom a hysterectomy is the proposed 'definitive treatment', a second cone biopsy may be required before hysterectomy to avoid inappropriate treatment of an occult invasive lesion. PMID- 11762661 TI - Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis. AB - Obstetric cholestasis is a liver disorder unique to pregnancy, which typically presents with pruritus. However, pruritus is common in pregnancy and the diagnosis of obstetric cholestasis is confirmed by finding abnormal liver function. We report 10 cases in which pruritus occurred before any abnormality in liver function tests (including total serum bile acids) and discuss the implications of this for clinical practice. PMID- 11762662 TI - The impact of the menstrual cycle on urinary symptoms and the results of urodynamic investigation. AB - Four hundred and eighty-three consecutive women referred for videocystourethrography completed a structured questionnaire about their menstrual status and urinary symptoms. Women were included in the study if they were premenopausal, had a regular menstrual cycle and were not taking hormonal therapy. One hundred and thirty-three women satisfied the inclusion criteria of whom 55 (41%) complained that their urinary symptoms were cyclical. The times at which symptoms were said to be at their worst were reported by the women as follows: during a period (n = 20; 36%); just after a period (n = 4; 7%); middle of the month (n = 8; 15%); just before a period (n = 23; 42%). The prevalence of abnormal detrusor activity on videocystourethrography increased significantly with time from the last menstrual period (chi2 for trend = 6.56, P = 0.01) and might reflect increases in the circulating level of progesterone following ovulation. This study provides further indirect evidence that progesterone could have an adverse effect on female lower urinary tract function. In addition, it might be necessary to consider the stage within the menstrual cycle when interpreting the results of urodynamic investigation. PMID- 11762663 TI - Pyoderma gangrenosum of the vulva. PMID- 11762664 TI - Meckel's diverticulitis: an uncommon complication during pregnancy. PMID- 11762665 TI - Interview with Bill Robertson. PMID- 11762666 TI - Acute ethylene chlorohydrin poisoning: experience of a poison control center. AB - BACKGROUND: Ethylene chlorohydrin (CAS 107-07-3), a chemical once used in hastening grape vine sprouting in Taiwan, has caused severe toxicity upon acute exposure. Although such use of ethylene chlorohydrin is now prohibited in Taiwan, poisoning still occurs following its illegal use. Since data concerning human ethylene chlorohydrin poisoning remain rare, we report our experience in treating acute ethylene chlorohydrin-poisoned patients. METHODS: A retrospective analysis was conducted to evaluate patients with ethylene chlorohydrin poisoning reported to Taiwan Poison Control Center during 1985-1998. RESULTS: Seventeen patients with ethylene chlorohydrin poisoning were identified. There were 11 male and 6 female patients, ranging in age from 2 to 70 years (median 53 years). The intent of exposure was suicide in 5, accident in 9, and occupational exposure in 3 patients. Oral ingestion was the most common route of exposure (14 patients). Seven out of the 17 patients died within 24 hours due to metabolic acidosis and respiratory failure. Ethanol therapy, used in 2 patients, had no apparent benefit. Moderate or mild poisoning was characterized by gastrointestinal effects only and an uneventful recovery. CONCLUSIONS: Ethylene chlorohydrin can result in severe metabolic acidosis, respiratory failure, coma, and death after acute exposure. PMID- 11762667 TI - Atropine use in Centruroides scorpion envenomation. AB - BACKGROUND: Systemic scorpion envenomation may be associated with hypersalivation and respiratory distress. Atropine can dry secretions, but is not recommended for stings from many foreign scorpions, since it exacerbates adrenergic toxicity to the cardiopulmonary system. Serious adrenergic effects, however, are rare with Centruroides sculpturatus envenomation. CASE SERIES: Five cases of Grade IV C. sculpturatus envenomation whose treatment included atropine were found on retrospective review at one poison control center located in a scorpion-endemic area. No clinically significant adverse effects of atropine were noted. In 3 cases, atropine's reversal of hypersalivation and respiratory distress obviated the need for further interventions. PMID- 11762668 TI - How long after drug ingestion is activated charcoal still effective? AB - OBJECTIVE: The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion. METHODS: This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies. CONCLUSION: Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose. PMID- 11762669 TI - Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. AB - OBJECTIVE: To correlate serum glycolic acid levels with clinical severity and outcome in ethylene glycol poisoning and to determine if glycolic acid levels are predictive of renal failure and the need for hemodialysis. METHODS: We measured serum ethylene glycol and glycolic acid levels by gas chromatography/mass spectrometry for 41 admissions (39 patients) for ethylene glycol ingestion and performed retrospective chart reviews. RESULTS: Eight patients died, all of whom developed acute renal failure. Of the survivors, 15 also developed acute renal failure, whereas 18 did not. Of those with normal renal function, 8 had glycolic acid levels below detection limits (< 0.13 mmol/L) despite ethylene glycol levels as high as 710 mg/dL; 7 of these patients coingested ethanol. Pertinent initial laboratory data for each group are as follows (mean; range): Deceased: pH 6.99 (6.82-7.22); bicarbonate, 4.8 mmol/L (2-9); anion gap, 28.6 mmol/L (24-40); glycolic acid, 23.5 mmol/L (13.8-38.0); ethylene glycol, 136.5 mg/dL (6-272). Survived/acute renal failure: pH 7.07 (6.75-7.32); bicarbonate, 5.6 mmol/L (1 12); anion gap, 28.7 mmol/L (18-41); glycolic acid, 20.2 mmol/L (10.0-30.0); ethylene glycol, 238.8 mg/dL (12-810). No acute renal failure with glycolic acid > 1.0 mmol/L: pH 7.29 (7.12-7.46); bicarbonate, 14.7 mmol/L (4-23); anion gap, 16.5 mmol/L (10-26); glycolic acid, 6.8 mmol/L (2.6-17.0); ethylene glycol, 269.1 mg/dL (6-675). No acute renal failure with glycolic acid < 1.0 mmol/L: pH 7.41 (7.38-7.47); bicarbonate, 23.4 mmol/L (17-25); anion gap, 11.8 mmol/L (8-18); glycolic acid, 0.1 mmol/L (0-0.66); ethylene glycol, 211 mg/dL (8-710). The mean time postingestion to admission generally correlated with severity as follows: deceased, > or = 10.4 h; survived/acute renal failure, > or = 9.9 h; no acute renal failure with glycolic acid > 1.0 mmol/L, > or = 6.2 h; no acute renal failure with glycolic acid < 1.0 mmol/L, > or = 3.7 h. Hematuria was more prevalent than oxaluria (86% and 41%, respectively), but neither was individually predictive of acute renal failure. Good correlations were found between glycolic acid levels and anion gap (r2 = 0.7724), pH (r2 = 0.7921), and bicarbonate (r2 = 0.6579); poor correlations (r2 < 0.0023) occurred between ethylene glycol levels and glycolic acid, pH, anion gap, and bicarbonate. Measured ethylene glycol values were highly correlated with ethylene glycol values calculated from the osmolal gap (r2 = 0.9339), but the latter overestimates the true value by about 7%, on average. An initial glycolic acid level > or = 10 mmol/L predicts acute renal failure with a sensitivity of 100%, a specificity of 94.4%, and an efficiency of 97.6%. Ethylene glycol levels are not predictive of acute renal failure or central nervous system manifestations of toxicity. If only ethylene glycol values are available (measured or calculated), an initial anion gap > 20 mmol/L is 95.6% sensitive and 94.4% specific for acute renal failure when ethylene glycol is present. Likewise, initial pH < 7.30 is 100% sensitive and 88.5% specific for acute renal failure. CONCLUSION: We propose glycolic acid > 8 mmol/L as a criterion for the initiation of hemodialysis in ethylene glycol ingestion. Patients with glycolic acid < 8 mmol/L probably do not need dialysis, regardless of the ethylene glycol concentration, when metabolism of ethylene glycol is therapeutically inhibited. In the absence of glycolic acid values, an anion gap > 20 mmol/L or pH < 7.30 predicts acute renal failure. PMID- 11762670 TI - Acute poisoning with the neonicotinoid insecticide imidacloprid in N-methyl pyrrolidone. AB - BACKGROUND: Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2 ylideneamine, CAS 138261-41-3] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals because they have resistant nicotinic receptor subtypes compared to insects, as well as protection of the central nervous system by the blood brain barrier. Despite wide usage, human exposure experience resulting in toxicity is quite limited. CASE REPORT: Here, we report a case of acute ingestion of an insecticide formulation containing 9.7% imidacloprid, <2 % surfactant, and the balance as solvent, N-methyl pyrrolidone. Clinical manifestation included drowsiness, disorientation, dizziness, oral and gastroesophageal erosions, hemorrhagic gastritis, productive cough, fever, leukocytosis, and hyperglycemia. The patient recovered without complication with supportive treatment and was discharged 4 days after ingestion. Follow-up barium upper gastrointestinal examination 1 month later was normal. Because moderate to high dose imidacloprid in animals causes central nervous system activation similar to nicotine, including tremors, impaired pupillary function, and hypothermia, it is unclear whether imidacloprid had a causal role in the patient's initial drowsiness and dizziness. It is more likely that the formulation ingredients, particularly N-methyl pyrrolidone, caused most of the clinical symptoms including minor central nervous system depression, gastrointestinal irritation, and hyperglycemia. PMID- 11762671 TI - Alkaline esophagitis evaluated by endoscopic ultrasound. AB - CASE REPORT: Two patients with corrosive esophagitis caused by alkaline household agents were examined with endoscopic ultrasound using a 20-MHz probe. In the first case, endoscopic ultrasound revealed circumferentially thickened mucosa and muscularis propria, and lack of differentiation between the mucosa and submucosa. However, esophageal stricture did not develop during 3 months of follow-up, suggesting that the deep lesion may have involved a narrow section of esophagus only. In the second case, a markedly thickened mucosa was seen, resulting in no sequelae. Endoscopic ultrasound offers a more accurate evaluation of the depth of the lesions in alkaline esophagitis compared to standard endoscopy or computed tomography. Longitudinal studies are needed to identify lesions at greatest risk for progression to stricture. PMID- 11762672 TI - Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. AB - CASE REPORT: We report a case of methanol poisoning exhibiting complete recovery from severe visual impairment following treatment with ethanol, fomepizole, and hemodialysis. An adult male presented with central blindness after ingesting methanol. Initial visual acuity was <20/800 (finger counting at 1-2 feet) with retinal edema on fundoscopy, arterial pH 7.19, methanol 97 mg/dL (30 mmol/L), formate 14.3 mmol/L, and ethanol undetectable. The patient was treated with ethanol, then fomepizole intravenously (15, 10, then 5 mg/kg), and hemodialysis. Methanol metabolism was effectively blocked by fomepizole even after ethanol had been eliminated, and the patient recovered 20/20 vision by day 14 with normal fundoscopy. This case report confirms highly efficient inhibition of alcohol dehydrogenase by fomepizole, as well as demonstrate the safety of fomepizole in a patient already exhibiting end-organ retinal toxicity. The potential for fomepizole to inhibit retinol dehydrogenase, an isoenzyme of alcohol dehydrogenase essential to vision, did not appear to be clinically significant in this symptomatic methanol-poisoned patient. PMID- 11762674 TI - Severe reversible bone marrow suppression induced by Selaginella doederleinii. AB - CASE REPORT: We report a 52-year-old female patient with cholangiocarcinoma who developed severe bone marrow suppression after taking Selaginella doederleinii as an alternative anticancer treatment. She developed severe pancytopenia with initial presentations of skin ecchymosis, itching, and gum bleeding 2 weeks after taking Selaginella doederleinii daily. Bone marrow smear and biopsy showed severe hypocellularity with no malignant cell infiltration. Approximately 1 week after stopping Selaginella doederleinii, her hemogram returned to previous levels. Selaginella doederleinii, a popular anticancer herb, may contain an as yet unidentified substance that contributes to reversible bone marrow suppression. PMID- 11762673 TI - Organ procurement and successful transplantation after malathion poisoning. AB - BACKGROUND: One of the major limitations to organ procurement and donation is the lack of suitable donors. As the demand for suitable organs exceeds the supply, identification of potential donors continues to evolve. Due to perceived risks of transmittable toxins and insufficient understanding of toxicological fate, poisoned patients are often overlooked as organ donors. CASE REPORT: A 17-year old white male was found by his mother having a seizure in bed. A strong odor of pesticides was noted and an empty container of malathion was found. He was transported to an outlying hospital and underwent prolonged cardiopulmonary resuscitation. The patient exhibited symptoms consistent with cholinergic poisoning and received a total of 12 mg of atropine and a pralidoxime bolus of 1 g followed by an infusion at 500 mg/h. Initial plasma cholinesterase was 1433 IU/L (normal 7500-14,600). The patient developed aspiration pneumonia and remained comatose. No further treatment for cholinergic toxicity was needed 5 days after admission and a cerebral blood flow scan confirmed brain death. After review of the available literature on the disposition andfate of malathion in human tissues, the patient's liver and kidneys were harvested for transplantation. The recipients were all doing well 1 year posttransplantation. CONCLUSIONS: This case of successful transplantation after organophosphate exposure underscores the fact that poisoned patients should not be overlooked as transplant candidates. Decisions should be based on the clinical presentation and knowledge of the properties of the toxin. PMID- 11762675 TI - Sustained-release potassium chloride overdose. AB - BACKGROUND: Although ingestion of sustained-release potassium supplements can cause life-threatening hyperkalemia in patients with abnormal renal function, only a few previous reports suggest that this may occur in patients with normal renal function. We report 2 cases of hyperkalemia in patients with normal renal function who developed hyperkalemia after ingesting sustained-release potassium preparations and describe the use of radiography and whole-bowel irrigation in their care. CASE REPORTS: The first patient is a 50-year-old woman who ingested 100 K-Dur tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 1 hour prior to presenting to the emergency department. She developed a peak serum potassium level of 9.7 mEq/L and had transient, potentially life-threatening electrocardiographic changes. The second patient was a 17-year-old man who ingested 20 to 30 Klor-Con tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 10 hours prior to presentation. Although he developed a peak serum potassium level of 6.1 mEq/L, he had a persistently normal electrocardiogram. In both patients, the tablets were visualized on abdominal radiographs and the gastrointestinal tracts of both were successfully decontaminated using whole-bowel irrigation. DISCUSSION: Although the sensitivity and specificity are unknown, the abdominal radiograph appears to be useful in detecting sustained-release potassium tablets. Whole-bowel irrigation as a primary method of gastrointestinal decontamination also appears to be effective although its use is not previously reported for sustained-release potassium overdoses. PMID- 11762676 TI - Tricyclic antidepressant fatality: postmortem tissue concentrations. PMID- 11762677 TI - Establishing a cause of death dependent upon time of postmortem. PMID- 11762678 TI - Diagnosis of unsuspected gamma hydroxy-butyrate poisoning by proton NMR. PMID- 11762679 TI - The value of noninvasive studies of parotid glands in primary Sjogren's syndrome. PMID- 11762680 TI - Clinical stratification in the spondylarthropathies: E. pluribus unum or ex uno plures? PMID- 11762681 TI - Phenotypic diversity is not determined by independent genetic factors in familial spondylarthropathy. AB - OBJECTIVE: To analyze the segregation of manifestations belonging to the spectrum of spondylarthropathy (SpA) among patients and unaffected siblings within SpA multiplex families. METHODS: Ninety-five multiplex families have been investigated. The diagnosis of SpA was made according to European Spondylarthropathy Study Group criteria. The prevalence of SpA manifestations was determined in unaffected siblings and compared with their prevalence in patients. RESULTS: We compared 241 SpA patients with 259 unaffected siblings. The prevalence of skeletal and extraarticular features not used as diagnostic criteria, i.e., radiographic sacroiliitis, peripheral enthesitis, uveitis, psoriasis, and inflammatory bowel disease, was significantly increased in patients compared with unaffected siblings. This result was not accounted for by sex or HLA-B27 distribution differences. CONCLUSION: In familial SpA, skeletal and extraarticular manifestations tend to segregate together, implying that all subsets are predominantly determined by a shared component, and that accessory factors must be responsible for phenotype diversity. PMID- 11762682 TI - Psoriasis predicts a poor short-term outcome in patients with spondylarthropathy. AB - OBJECTIVE: The outcome of patients with recent-onset spondylarthropathy (SpA) is unclear. Therefore, the objective of this study was to prospectively correlate clinical and laboratory features with functional and radiologic outcome in patients with psoriatic SpA (PsS), undifferentiated SpA (uSpA), and Reiter's syndrome/reactive arthritis (ReA). METHODS: Patients presenting to an early arthritis clinic with a spondylarthropathy pattern of peripheral arthritis were selected and prospectively followed. Clinical and laboratory features were recorded at baseline, 12 months, and 24 months. Radiographs of affected joints were taken at presentation and at followup. RESULTS: The cohort consisted of 157 patients: 82 PsS, 59 uSpA, and 16 ReA. Symptom duration at presentation was progressively shorter, and the erythrocyte sedimentation rate/C-reactive protein (ESR/CRP) incrementally higher in ReA, uSpA, and PsS, respectively. There was a higher swollen joint count (SJC) in PsS compared with uSpA. In PsS, strong positive correlations were observed between ESR/CRP and articular indices. Initially, functional impairment was greater in ReA compared with uSpA and PsS but resolved completely in ReA. Clinical remission rates at 2 years were ReA 61% and uSpA 63%, compared with PsS 14%. Remission at 2 years could be predicted in SpA by disease category and presentation SJC. Baseline erosions in PsS (28%) and uSpA (5%) increased to 45% and 25%, respectively, at 2 years. CONCLUSION: These observations suggest a spectrum within the spondylarthropathy subgroups where at presentation the acute phase markers in ReA and uSpA reflect a systemic process, whereas in PsS they reflect articular manifestations. Although the clinical presentations are indistinguishable, PsS has a more aggressive clinical course with a poorer functional and radiologic outcome. PMID- 11762683 TI - A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992. AB - OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients. PMID- 11762684 TI - A health professional's guide to exercise prescription for people with arthritis: a review of aerobic fitness activities. PMID- 11762685 TI - Magnetic resonance imaging and magnetic resonance sialography of parotid glands in primary Sjogren's syndrome. AB - OBJECTIVE: To look for structural parotid gland changes on magnetic resonance (MR) imaging and MR sialography of primary Sjogren's syndrome (SS) patients and healthy control subjects and to compare these methods with each other. METHODS: MR imaging and MR sialography of both parotid glands were performed on 26 patients and 7 healthy controls. Bilateral surface coils were used to obtain high spatial resolution. RESULTS: Twenty-two of the 26 patients had abnormalities on MR imaging. Twenty-one had a nodular or dendritic parenchymal pattern, 5 had cavities, and 6 had duct dilatations. On MR sialography, 25 of the 26 patients had abnormalities of the ducts, and 16 of them also had cavities. One patient and all 7 controls had normal results with both methods. The structural appearance of the parotid glands on MR images had marginal linear association with the duct system changes but no correlation with the cavitary changes seen on MR sialography. Furthermore, duct system abnormalities did not correlate with cavitary changes. Both parenchymal and sialographic abnormalities were associated with the presence of Ro/SSA antibodies but not with age of the patient, disease duration, salivary flow rate, or the presence of hypergammaglobulinemia or extraglandular manifestations. CONCLUSION: MR imaging and MR sialography are noninvasive methods that provide definitive information of morphologic changes in parotid glands and can be used as diagnostic indicators of primary SS. Because these methods give information on different aspects of glandular pathology, both should be performed when evaluating parotid glands of SS patients. MR sialography is more sensitive, but conventional MR imaging gives complementary information on the progressive pathologic changes of glandular parenchyma. PMID- 11762686 TI - Effect of a randomized, controlled trial of exercise on mood and physical function in individuals with fibromyalgia. AB - OBJECTIVE: To evaluate the effect of exercise on mood and physical function in individuals with fibromyalgia. METHODS: Subjects were randomly assigned to an exercise (EX) or control (CTL) group. EX subjects participated in 3 30-minute exercise classes per week for 23 weeks. Subjects were tested at entry and at 6, 12, and 23 weeks. Tests included the Beck Depression Inventory (BDI), 6-minute walk, State-Trait Anxiety Inventory (STAI), Mental Health Inventory (MHI), Fibromyalgia Impact Questionnaire (FIQ), Arthritis Self-Efficacy Scale (ASES), and a measure of tender points and knee strength. RESULTS: Fifty subjects (27 EX, 23 CTL) completed the study, and 31 (15 EX, 16 CTL) met criteria for efficacy analyses. In efficacy analyses, significant improvements were seen for EX subjects in 6-minute walk distances, BDI (total, cognitive/ affective), STAI, FIQ, ASES, and MHI (3 of 5 subscales) scores. These effects were reduced but remained during intent-to-treat analyses. CONCLUSION: Exercise can improve the mood and physical function of individuals with fibromyalgia. PMID- 11762687 TI - Microscopic polyangiitis presenting as pulmonary-renal syndrome in a patient with long-standing diffuse cutaneous systemic sclerosis and antibodies to myeloperoxidase. PMID- 11762688 TI - Glucosamine and chondroitin sulfate for the treatment of osteoarthritis: comment on the article by Akama and Saito. PMID- 11762689 TI - Rheumatoid arthritis: an ancient disease or a new one? PMID- 11762690 TI - The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats. AB - We studied the effect of oral ascorbic acid treatment on nickel sulfate-induced lipid peroxidation in the liver of Wistar strain male albino rats. Lipid peroxide and glutathione levels and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in liver. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased glutathione, SOD, CAT, and GSH-Px activities in liver. The simultaneous administration of ascorbic acid with nickel sulfate resulted in a remarkable improvement of lipid peroxide, glutathione, SOD, CAT, and GSH-Px status in liver in comparison with rats treated with nickel alone. Nickel sulfate has an adverse effect on hepatic lipid peroxidation in animals, but simultaneous treatment with ascorbic acid offers a relative protection against nickel-induced hepatotoxicity. PMID- 11762691 TI - Effects of acamprosate and scopolamine on the working memory of rats in a three panel runway task. AB - The aim of this study was to evaluate the effect of treatment with single (1x) and multiple (10x) doses of the anti-craving compound acamprosate (AC, calcium acetyl homotaurinate) on working memory in rats, using in a three-panel runway test. We measured tasks after the animals were treated with AC (500 mg/kg/d, i.p.); scopolamine (SC, 0.5 mg/kg/d, i.p.), a cholinergic muscarinic receptor antagonist; or both drugs concomitantly (ACSC), either for 1 day (1x) or daily for 10 consecutive days (10x). Neither 1x not 10x AC alone had a significant effect on working memory task performance, whereas treatment with SC alone had a significantly negative effect on the ability of the rats to complete the tasks. Rats receiving ACSC performed better than those receiving SC alone, making fewer errors and displaying shorter latency, similar to the performance of the control group. These observations support the hypothesis of an indirect involvement of AC in the cholinergic system. PMID- 11762692 TI - Possible mechanisms for the anti-implantation action of dicofol in albino rats. AB - Dicofol, a chlorinated pesticide showing estrogenic activity, was administered orally to virgin pregnant rats at doses of 300, 400, 500, 600, or 700 mg/kg/day for 7 consecutive days to examine its effect on blastocyst implantation. One group of rats received estradiol-17beta (10 microg) for comparison and control animals received similar quantities of olive oil. Autopsy on day 8 revealed that the olive-oil treated rats were pregnant and had a normal number of implantations and a normal duration of diestrus. Treatment with estradiol-17beta completely inhibited implantation, significantly decreased the duration of diestrus with concomitant increase in estrus. Treatment with 300, 400, or 500 mg/kg/d dicofol neither inhibited implantation nor significantly changed diestrus. Treatment with 600 mg dicofol partially inhibited implantation and significantly decreased diestrus with concomitant increase in estrus. Treatment with 700 mg dicofol completely inhibited implantation, and the uterus showed placental scars. This group exhibited a significant decrease in diestrus with concomitant increase in estrus. In all dicofol-treated rats, no significant changes were found in body weight or organ, except for a significant decrease in the weight of the uterus in groups receiving either 700 mg dicofol or estradiol-17beta. The inhibitory effect of dicofol on implantation may be due to an imbalanced estrogen-progesterone ratio, essential for implantation. The pesticide is neither tubal locking nor causes expulsion of the blastocyst from the uterus like estradiol-17beta. PMID- 11762694 TI - Effect of hyperoxia and metformin on vascular responses to vasoactive compounds in rats. AB - Exposure of cells to oxygen concentrations higher than normal (hyperoxia) damages the molecular components of cells, resulting in cellular dysfunction and death. Metformin, a biguanide molecule used for treating non-insulin-dependent diabetes, been shown to lower blood pressure. The aim of this study was to investigate the possible effects of hyperoxia and metformin on the vascular responses of thoracic aorta to vasoactive compounds, using an in vitro rat model. In the hyperoxia control (HC) group, the response to acetylcholine was completely abolished, but metformin treatment before (MH) or after (HM) exposure to 100% oxygen restored the response to acetylcholine to near-control values. In aortas from HC, MH, or HM groups, no significant differences were found in pD2 values to the endothelium dependent vasodilator sodium nitroprussiate. In aortic strips from metformin treated rats, the pD2 values for noradrenaline in the presence of endothelium were significantly smaller than those in the normal control group. The maximal contractile responses to KCl were not significantly different among all experimental groups. The results of the present study show that in hyperoxia exposed rats, metformin treatment reverses the abolished vascular relaxation to AChe. PMID- 11762693 TI - Effect of 5-aminoimidazole-4-carboxamide riboside (AICA-r) on isolated thoracic aorta responses in streptozotocin-diabetic rats. AB - Diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. 5-amino-4-imidazole-carboxamide riboside (AICA-r), a nucleoside corresponding to AICA-ribotide and an intermediate of the de novo pathway of purine biosynthesis, was recently proposed as a new insulinotropic tool in non insulin-dependent diabetes mellitus. The aim of the present study was to define whether AICA-r affects altered vascular responsiveness to vasoconstrictors and vasodilators in the thoracic aorta of neonatal streptozotocin (STZ)-diabetic rats. The results of this study indicate that a 1-month treatment with AICA-r significantly increases the body weight in diabetic rats; significantly decreases the blood glucose level of diabetic rats (from 302+/-47 to 135+/-11 mg/dL, p<0.001); does not significantly affect the fast, slow, and total components of responses to noradrenaline in all the experimental groups; reverses the increased Emax values of noradrenaline in diabetic rats to near-control values; reverses the completely abolished responses of acetylcholine (pD2 and percent relaxation) in diabetic rats to control values; and reverses the decreased pD2 values of sodium nitroprussiate in diabetic rats to control values. In conclusion, AICA-r treatment in neonatal STZ-diabetic rats improved increased blood glucose levels, accelerated weight gain, reversed endothelial dysfunction, and normalized vascular responses. PMID- 11762695 TI - Effect of nitric oxide synthase inhibition on the gastric mucosal barrier in rats. AB - The aim of this study was to investigate the effect of N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the gastric mucosal barrier in rats. A group of Swiss albino rats received L-NAME (60 mg/kg/d) in their drinking water daily for 21 d. The mucin and prostaglandin E2 (PGE2) contents of the gastric mucosa were measured in gastric tissue samples. L-NAME intake did not affect gastric mucin, but it significantly reduced PGE2, a component of the gastric mucosal barrier. The results of this study imply that nitric oxide plays an important mediatory role in maintaining the gastric mucosal barrier. The inhibition of nitric oxide may be involved in the increased vulnerability of the gastric mucosa to injurious stimuli in rats. PMID- 11762696 TI - Gender difference in cytoprotection induced by estrogen on female and male bovine aortic endothelial cells. AB - Before menopause, women have a lower risk of cardiovascular diseases than men. Studies attribute this gender difference to estrogenic protection in the female cardiovascular system. We have demonstrated that 17beta-estradiol (E2) protects female bovine aortic endothelial cells against oxidative injury, probably through the induction of antioxidant enzyme activities. In this study, we examined whether E2 confers a differential protection on male and female cells. Bovine aortic endothelial cells from both genders were preconditioned for 24 h with E2 (1 nM to 10 microM), and their resistance to paraquat (1 mM, 3 h), a superoxide generator, was measured using an MTT assay. In contrast to the protection observed in female bovine aortic endothelial cells, there was no protective effect by E2 on male bovine aortic endothelial cells at physiologic concentrations. However, E2 at 1-10 microM attenuated paraquat's toxicity in both male and female cells, probably through its direct antioxidant activity. E2 at 1 nM increased in female, but not in male, cells the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, which was associated with decreased levels of reactive oxygen species during subsequent paraquat exposure. This suggests that antioxidant enzyme induction plays some role in E2-augmented oxidative resistance in female endothelial cells. PMID- 11762697 TI - Relaxin has a minor role in rat mammary gland growth and differentiation during pregnancy. AB - Growth and differentiation of mammary gland is associated with numerous hormones and a variety of cell-cell, cell-matrix interactions. This study addressed the role of relaxin (Rlx) on these processes. Morphologic and biochemical changes that occur throughout the second half of pregnancy are reported. Temporal patterns and spatial distributions of markers useful to evaluate proliferation, secretion, and collagen remodeling were established. To evaluate the role of Rlx, an ablation/replacement animal model was used. Considering Rlx secretion pattern, two periods were selected: d 11 through d 13, and d 20 through d 23. In the stroma, the extracellular compartment showed changes associated with the lack of Rlx. Collagen remodeling within the lobuloalveolar structure, measured by a significant increase in collagen birefringence, decreased at d 12, d 21, and d 22. Parenchymal structures were less sensitive to the absence of Rlx than stroma. Epithelial cell proliferation was lower in Rlx-deficient rats only at d 12, and alpha-lactalbumin expression decreased at d 21 and d 22. Both lobuloalveolar diameter and percentage of area occupied by these structures showed no changes. In the absence of Rlx, some of the studied markers showed statistically significant differences in scattered days; these do not make clear trends. No differences were found on d 23 on any of the studied parameters suggesting that compensatory mechanisms might be activated to overcome the effects of the absence of Rlx. Unlike the critical role of Rlx either in uterine cervix dilation or in nipple development during rat pregnancy, Rlx had a minor role in growth and differentiation of rat mammary gland. PMID- 11762698 TI - Herbimycin, a tyrosine kinase inhibitor with Src selectivity, reduces progesterone and estradiol secretion by human granulosa cells. AB - The purpose of the present study was to investigate whether the tyrosine kinase inhibitor herbimycin with some selectivity to block Src would alter the stimulatory effects of follicle-stimulating hormone (FSH) and cyclic adenosine monophosphate (cAMP) on estradiol secretion by human granulosa cells. Granulosa cells were taken from ovaries of premenopausal women undergoing oophorectomy for reasons unrelated to ovarian pathology. Granulosa cells from follicles ranging from 5-20 mm in diameter were subjected to culture. Granulosa cells were cultured with human FSH (2 ng/mL) or cAMP (0-1 mM) and testosterone (1 microM) in the presence and absence of herbimycin (0-2 pM). Media were collected at 24, 48, and 72 h. Accumulation of cAMP, progesterone, and estradiol in the media was determined by radioimmunoassay. Herbimycin dose dependently inhibited the ability of FSH to induce increases in progesterone and estradiol secretion. Although herbimycin increased (p < 0.0001) the accumulation of cAMP in response to FSH, this was evident only at the high concentrations of herbimycin (2 microM). To determine whether herbimycin would inhibit the ability of exogenous cAMP to induce estradiol and progesterone secretion, granulosa cells were incubated with 0-1 mM cAMP in the presence and absence of various doses of herbimycin. Herbimycin inhibited cAMP-induced estradiol and progesterone secretion in granulosa cells. The results from seven experiments indicate that herbimycin inhibits FSH stimulation of estradiol and progesterone secretion and that this inhibition may be, in part, at post-cAMP site(s). PMID- 11762700 TI - Suppression by exendin(9-39)amide of glucagon-like peptide-1 insulinotropic action in rats infused with dimethyl ester of succinic acid. AB - Glucagon-like peptide-1 (GLP-1) acts as a nutrient-dependent insulin-releasing agent, and its insulinotropic action is enhanced by nutrient secretagogues, such as the dimethyl ester of succinic acid (SAD). In the present study, a primed constant infusion of SAD (0.5 micromol followed by 0.25 micromol/min both per g of body wt) was found to increase plasma insulin concentration in fed anesthetized rats, to potentiate the B-cell secretory response to GLP-1 (0.5 pmol/g of body wt), and to unmask the hypoglycemic potential of the gastrointestinal hormone. In the SAD-infused rats, the infusion of exendin(9 39)amide (5.0 pmol/min per g of body wt), 1 min before and 3 min after GLP-1 injection, decreased plasma insulin concentration before GLP-1 injection, suppressed the B-cell secretory response to GLP-1, and both delayed and minimized its hypoglycemic action. It is proposed, therefore, that exendin (9-39)amide could represent a tool in the treatment of alimentary or reactive hypoglycemia. PMID- 11762699 TI - A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia. AB - Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH. PMID- 11762701 TI - Dual role of glucocorticoids in suckling-induced prolactin secretion. AB - The exact contribution of corticosteroids to the control of prolactin secretion in lactating rats is poorly understood. Therefore, the present studies were focused on the effect of adrenalectomy and dexamethasone treatment on the suckling-induced prolactin release. Animals were adrenalectomized on the 3rd day of lactation and tested on the 7th day of lactation. In adrenalectomized animals, the suckling stimulus failed to induce the characteristic increase in plasma prolactin levels. Dexamethasone pretreatment (400 microg/kg b.w. s.c. 24, 48, 72 h before testing) of adrenalectomized rats restored this prolactin response. The same treatment with dexamethasone given to control animals attenuated the suckling stimulus induced prolactin response. The present findings indicate that corticosteroids are essential for a basic prolactin response of lactating rats. PMID- 11762702 TI - Effects of 17beta-estradiol on the expression of matrix metalloproteinase-1, -2 and tissue inhibitor of metalloproteinase-1 in human osteoblast-like cell cultures. AB - Estrogen can effectively prevent estrogen deficiency-induced bone loss in animals and humans. However, its mechanism remains unknown. Osteoblast-derived Matrix metalloproteinse-1 (MMP-1), MMP-2, and tissue inhibitor of metalloproteinase-1 (TIMP-1) recently were implicated as playing important roles in initiating bone resorption. Therefore, we tested the effects of 17beta-estradiol (E2) on MMP-1, MMP-2, and TIMP-1 production in cultures of human osteoblastic MG-63 cells and normal human osteoblasts (hOB). MMP-1, MMP-2 and TIMP-1 concentrations in the culture medium were determined by ELISA, and activity of MMP-2 was assessed by ELISA. After 12-48 h of treatment, E2 at 10(-8)M decreased MMP-1 level in cultures of MG-63 cells or hOB. Treatment with increasing, dose of E2 in MG-63 cells or hOB caused a dose-dependent decrease in MMP-1 synthesis. E2 had no influence on MMP-2 and TIMP-1 production in MG-63 cells or hOB cultures, as well as activation of latent MMP-2. In conclusion, E2 represses MMP-1 synthesis, and this effect may contribute to its action on the inhibition of bone resorption, followed by prevention of bone loss. Increasing MMP-1 production followed by estrogen deficiency may contribute to the mechanisms involved in postmenopausal osteoporosis. PMID- 11762703 TI - Effects of thyroid hormone on the renal dopaminergic system. AB - This study determined the effects of thyroid hormone on the renal dopaminergic system. Surgical thyroidectomy (Tx) and treatment with 2-thiouracil (Thio) decreased renal cortex Na+/K+ ATPase activity and urinary volume. Tx also decreased urinary Na+ and urinary L-DOPA without changing urinary excretion of Dopamine (DA). Thio treatment decreased slightly urinary L-DOPA and Na+, but increased urinary excretion of DA. In both models of thyroid hormone deficiency, the ratio urinary DA/DOPA increased. Changes after Thio treatment were reversed after one month of drug withdrawal. Treatment with T3 via osmotic minipump increased Na+/K+ ATPase activity and urinary L-DOPA, did not change urinary DA, and increased the ratio DA/DOPA. To further analyze the effects of thyroid hormone deficiency, we administered selective DA1 (SCH-23390), DA2 (Sulpiride), and a non selective (Haloperidol) DA receptor antagonists to Thio treated and control animals. The DA1 antagonist decreased diuresis, natriuresis and urinary L DOPA in control, but had no effect in Thio treated rats. Sulpiride had no effect in either group. The combination of SCH-23390 plus Sulpiride decreased urinary L DOPA and urinary volume only in Thio treated animals. Haloperidol decreased urinary volume in Thio treated animals, but had no effect in controls. Our findings suggest that renal DA synthesis is to some extent dependent on thyroid hormone levels, and that the response of DA receptors is altered by thyroid hormone deficiency, indicating a role of this hormone in the regulation of the renal dopaminergic system. PMID- 11762704 TI - Leptin levels in diabetic and nondiabetic subjects. AB - The role of leptin in human pathophysiology elicits considerable interest in view of its potential role as a treatment tool for obesity and other insulin resistant states, like type 2 diabetes mellitus (T2DM). Leptin has been extensively studied in obese humans, and much less so in other pathologic conditions. Leptin level has been reported to correlate with percent body fat mass (%FM), fasting serum insulin (FPI), insulin sensitivity and blood pressure. The aim of this study was to compare the leptin concentration, and its relationship with some anthropometric and biochemical parameters related to insulin resistance in 140 moderately obese type 2 diabetics (T2DM) and 160 age and weight matched non diabetic controls in order to get a better insight into the possible role of leptin in the metabolic abnormalities of diabetes. The leptin levels were lower in the diabetic population only when both sexes were combined (p < 0.05) and were higher in the females of both groups. Among the nondiabetics, the leptin levels appeared to be related to BMI, %FM, HDL and FPI, while this was not the case in the diabetics. After correction for BMI, leptin appeared to be correlated with the FPI levels only in the non-diabetic females. When plasma leptin was included in a multiple linear regression model with plasma leptin as a dependent variable, BMI, W:Hr and FPI levels were significantly related to leptin in the non diabetic population, while no relationship reached the level of statistical significance among the diabetics, with the exception of the borderline value for the FPI (p = .052). In conclusion, leptin levels were independent of any of the parameters examined in our diabetic population, possibly due to the progressive loss of the normal mechanisms of leptin regulation with advancing disease. Conclusive data can only be obtained from the longitudinal study of a cohort of newly diagnosed diabetic subjects. PMID- 11762705 TI - Differential effects of glutamate agonists and D-aspartate on oxytocin release from hypothalamus and posterior pituitary of male rats. AB - In order to determine whether ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptor activation modulates oxytocin release in male rats, we investigated the effect of agonists of both types of glutamate receptors on oxytocin release from hypothalamus and posterior pituitary. Kainate and quisqualate (1 mM) increased hypothalamic oxytocin release. Their effects were prevented by selective AMPA/kainate receptor antagonists. NMDA (0.01-1 mM) did not modify hypothalamic oxytocin release. Group I mGluR agonists, such as quisqualate and 3-HPG, significantly increased hypothalamic oxytocin release. These effects were blocked by AIDA (a selective antagonist of group I mGluRs). In the posterior pituitary, oxytocin release was not modified by kainate, quisqualate, trans-ACPD (a broad-spectrum mGluR agonist) and L-SOP (a group III mGluR agonist). However, NMDA (0.1 mM) significantly decreased oxytocin release from posterior pituitary. D-Aspartate significantly increased oxytocin release from the hypothalamus, while it decreased oxytocin release from posterior pituitary. AP-5 (a specific NMDA receptor antagonist) reduced the D-Aspartate effect in the hypothalamus, but not in the posterior pituitary. Our data indicate that the activation of non-NMDA receptors and group I mGluRs stimulates oxytocin release from hypothalamic nuclei, whereas NMDA inhibits oxytocinergic terminals in the posterior pituitary. D-Aspartate also has a dual effect on oxytocin release: stimulatory at the hypothalamus and inhibitory at the posterior pituitary. These results suggest that excitatory amino acids differentially modulate the secretion of oxytocin at the hypothalamic and posterior pituitary levels. PMID- 11762706 TI - Thyroidectomy induces neurofilament expression in adenohypophyses of rats. AB - We studied the effect of thyroidectomy on neurofilament expression in adenohypophyses of rats. The question of whether thyroxine (T4) administration can reduce this effect was also investigated. Rats were divided into: 1. Euthyroid controls, 2. Thyroidectomized 20 d (Tx 20 d), 3. Thyroidectomized 20 d with replacement of T4 (Tx 20 d + T4 20 d), 4. Thyroidectomized 40 d (Tx 40 d), 5. Thyroidectomized 40 d with replacement of T4 20 d after surgery (Tx 40 d + T4 20 d). Adenohypophyses were studied by immunohistochemistry and Western blot analysis using antibodies against neurofilament 200 kDa (NF-H) and thyroid stimulating hormone (TSH). The number of thyrotrophs with immunoreactivity for NF H was increased in Tx 20 d and Tx 40 d rats, whereas T4 administration protected the effect of thyroidectomy. In the thyroidectomized animals, thyrotrophs showed eccentric nuclei and the cytoplasm was full of NF-H immunoreactivity, whereas in T4 treated rats, the thyrotrophs were similar to control. Western blot analysis showed that NF-H expression increased in rats thyroidectomized for 20 and 40 d. T4 given immediately or 20 d after thyroidectomy caused no changes in NF-H expression. We conclude that thyroidectomy induces NF-H expression in adenohypophyses of rats and administration of T4 decreases this effect. PMID- 11762708 TI - Influence of nicotinamide on the radiosensitivity of normal and goitrous thyroid in the rat. AB - Radioiodine is used to treat thyroid cancer and hyperthyroidism. In order to reduce radiation hazard to the patient and to people in contact with the patient it would be desirable to obtain the same therapeutic effect with lower activities of the radioisotope. This could be achieved by the simultaneous administration of a compound that increases tissue radiosensitivity. In this study we analyzed the use of nicotinamide (NA) as a radiosensitizer to radioiodine, to increase 131I efficacy. NA administered during 30 days to Wistar rats failed to alter thyroid weight. The influence of NA on radiothyroidectomy induced by increasing doses of 131I was examined in otherwise nontreated rats. NA produced a significant increase in the ablation caused by radioiodine. Goiter was then induced by the administration of methylmercaptoimidazol (MMI) to rats, followed by the treatment with radioiodine with and without simultaneous administration of NA. Thyroid weight per 100 g of body weight ratio was not changed by NA alone; 131I administration caused a 25% decrease in goiter size, while 131I plus NA produced a reduction of the ratio of 46% (p < 0.01 vs. NA). No changes were observed in adenosine diphosphate (ADP)-ribosilation of thyroid nuclear protein in NA-treated rats. Thyroid blood flow (determined by 86Rb uptake) was increased by 84% by NA. In conclusion, nicotinamide has a significant radiosensitizing effect to 131I both in normal and goitrous rats. This action is because of an increase in thyroid blood flow, which probably enhances tissue oxgenation. PMID- 11762707 TI - Adrenalectomy regulates apoptotic-associated genes in rat hippocampus. AB - Morphological studies of granular neurons of the hippocampus have shown that adrenalectomy (ADX) induces the cell death of granular neurons, an effect prevented by corticosterone replacement. We addressed the hypothesis that corticosterone regulates the expression of the apoptotic bcl-2 gene family. Five days after adrenalectomy, we observed morphological changes related to hippocampal granule cell apoptosis that was accompanied by terminal dUTP nick and labeling (TUNEL) labeling in nuclei located in the hilus region. Corticosterone replacement prevented the cell death induced by ADX. Using RT-PCR we found a reduction in mRNA levels of the antiapoptotic gene bcl-2 in whole hippocampus, an effect which was prevented by corticosterone administration to ADX rats. However, Bcl-2 protein levels were not altered by this treatment. We did not observe modifications in the level of bcl-X(L) mRNA however, we did find a 40% reduction in Bcl-X(L) protein levels, an effect not reversed by corticosterone. In contrast, we found a reduction in the mRNA of the antiapoptotic gene bax and Bax levels after ADX; both effects were prevented by corticosterone. The reduction in proapoptotic bax and in antiapoptotic bcl-2 mRNA levels in the whole hippocampus, suggests that local variations in these molecules could account for both neuronal viability of the CA1-CA3 and granular cell death detected by morphological means and observed after ADX. PMID- 11762709 TI - Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats. AB - We evaluated the effects of hyperthyroidism on cardiac structural changes and postischemic myocardial function, and also studied how an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, can alter these changes. Hyperthyroidism was induced by daily intraperitoneal injection of thyroxine (T4) (600 microg/kg) with or without cilazapril (10 mg/kg per day, orally), and control rats were given by vehicle. After 2 weeks of treatment, T4-treated rats showed increases in blood pressure and heart weight to body weight ratio (HW:BW). Cilazapril decreased blood pressure to control values and reduced HW:BW. In the isolated working heart preparation, T4-treated rats showed a poor postischemic recovery of left ventricular pressure-rate product (14% of baseline at 30 minutes of reperfusion vs. vehicle 85%) and cardiac work (6% vs. 71%). Cilazapril recovered both values to 49% and 43%. Propranolol (500 mg/L in drinking water) decreased blood pressure to the same extent as cilazapril in hyperthyroid rats, but changed neither HW:BW nor the postischemic myocardial dysfunction. Percent recovery of cardiac work was inversely well correlated with HW:BW (R2 = 0.998, p < 0.001). Results indicate that T4-induced cardiac hypertrophy enhances postischemic cardiac dysfunction. Results also indicate renin-angiotensin system (RAS), but not sympathetic nerve activation, is involved in cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats. PMID- 11762710 TI - Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas. AB - Duox2, and probably Duox1 are glycoflavoproteins involved in the thyroid H2O2 generator functionally associated to thyroperoxidase (TPO). We investigated both DUOX1 and DUOX2 gene expressions using quantitative reverse transcription polymerase chain reaction (RT-PCR) in 47 thyroid carcinomas, including 10 paired normal/tumoral tissues. In carcinomas, variations of DUOX1 and DUOX2 mRNA levels were parallel, indicating that control mechanisms of both gene expressions operate in tumors as well as in normal thyroid tissues; DUOX1 expression was in the normal range in 20, was decreased up to 50-fold in 8, and increased up to 7 fold in 19 samples. DUOX2 expression was in the normal range in 15, was decreased up to 200-fold in 10, and increased up to 5-fold in 22 samples. In the 10 paired samples, variations of DUOX and TPO gene expressions were not correlated. We analyzed Duoxl/2 protein expression in 86 tumor samples using an antipeptide antiserum reacting with both Duox proteins. In normal tissue, Duox proteins are localized at the apical pole of thyrocytes, with 40% to 60% of thyrocytes being stained. In the 86 cancer tissues, immunostaining was absent in 19 samples, was low in 32, and normal or even slightly increased in the other 35 samples. The expression of Duox proteins was related to tumor differentiation, being more frequently found in neoplastic tissues that were able to pick up radioiodine, and in those with a detectable expression of sodium iodide symporter (NIS), pendrin and TPO. PMID- 11762711 TI - Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer. AB - Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasible, and malignant tissue ablation by 131I administration. This procedure requires levothyroxine withdrawal to obtain high levels of endogenous thyrotropin (TSH) to stimulate radioactive iodine uptake by the malignant tissue. Levothyroxine withdrawal may cause severe adverse effects and complications in patients with concomitant illness or advanced metastatic disease. The recent availability of recombinant human thyrotropin (rhTSH) allows diagnostic whole-body scan (WBS) and thyroglobulin testing without levothyroxine withdrawal. We describe six patients with metastatic differentiated thyroid cancer (DTC) and concomitant illness in whom the use of rhTSH was effective in preventing the complications that patients had previously experienced during hypothyroidism consequent to levothyroxine withdrawal. Our results indicate that rhTSH can be particularly advantageous to avoid signs and symptoms of hypothyroidism and complications because of associated diseases in view of 131I treatment of DTC metastases in selected cases in which levothyroxine withdrawal may be dangerous. Its efficacy to treat advanced metastatic disease should be further investigated. PMID- 11762712 TI - Iodine-131 treatment of thyroid papillary carcinoma in patients undergoing dialysis for chronic renal failure: a dosimetric method. AB - Until recently, the therapeutic protocol widely accepted for ablation of the thyroid remnant and for metastases of thyroid papillary carcinoma was the administration of 131I after surgery. However, at present, some data question the usefulness of such treatment in patients considered low risk. The treatment with radioiodine in patients suffering from end-stage renal disease (ESRD) undergoing hemodialysis requires controlled dosages and individualized administration guidelines. The need to include these patients on the waiting list for a renal transplantation, once they have overcome the disease, and the higher prevalence of thyroid carcinoma in ESRD patients makes this an increasingly significant problem. The cases reported in the literature are few and the therapeutic models followed are very difficult. In this paper we propose a therapeutic model that provides the highest thyroid ablative dosage, minimizing radiation exposure to the rest of the organs. The main difference between our protocol and that already described is the performance of daily hemodialysis during the first 5 days of treatment, as well as the administration of a dose of 131I equivalent to that administered to patients who show normal renal function. PMID- 11762713 TI - A thyroid-stimulating life: an interview with Dr. J. Maxwell McKenzie. PMID- 11762714 TI - Serum insulin-like growth factor type 1, insulin-like growth factor-binding protein-1, and insulin-like growth factor-binding protein-3 concentrations in patients with thyroid dysfunction. AB - Thyroid hormones play a role in the regulation of insulin-like growth factor type 1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) expression, and both IGF-1 and IGFBPs have been shown to be related to the function and growth of the thyroid. Our aim was to evaluate serum concentrations of IGF-1, IGFBP-1, and IGFBP-3 in patients with thyroid dysfunction before and after normalization of thyroid function. The study was performed in 86 patients with thyroid dysfunction (43 hyperthyroid and 43 hypothyroid patients) and 17 euthyroid subjects. Serum growth hormone (GH), insulin, IGF-1, IGFBP-1, and IGFBP 3 were measured in all patients before and after normalizing serum thyroid hormone concentrations. Hyperthyroid patients showed IGF-1 (198.8 +/- 17.0 microg/L) and IGFBP-3 levels (4.2 +/- 0.2 mg/L) similar to those found in the control group (217.9 +/- 20.3 microg/L and 4.2 +/- 0.3 mg/L, respectively). After therapy these levels significantly decreased to 156.6 + 11.1 microg/L (p < 0.01) and 3.3 +/- 0.1 mg/L (p < 0.001), respectively. IGFBP-1 concentrations were clearly higher than those found in controls (22.7+/- 2.6 vs. 5.7 +/- 1.5 microg/L, p < 0.001) and exhibited a significant reduction after therapy for thyroid hyperfunction (11.0 +/- 1.7 microg/L, p < 0.001). Patients with hypothyroidism showed serum concentrations of IGF-1 (161.5 +/- 13.1 microg/L, p < 0.05) and IGFBP-3 (3.2 +/- 0.3 microg/L, p < 0.05) significantly lower than those found in healthy volunteers. However, replacement therapy with levothyroxine did not induce any significant modification of these concentrations (152.6 +/- 10.6 microg/L and 3.2 +/- 0.2 mg/L, respectively). Similarly, patients with thyroid hypofunction exhibited raised levels of IGFBP-1 (15.5 +/- 0.9 microg/L, p < 0.05 vs. control group) that were significantly decreased after therapy (8.8 +/- 1.4 microg/L, p < 0.01). The results of the present study show that thyroid status affects GH/IGF axis. Hypothyroidism is associated with significant reductions of IGF-1 and IGFBP-3, and IGFBP-1 is elevated in both hypothyroidism and hyperthyroidism. PMID- 11762715 TI - Autoimmune thyroid disease in pregnancy and the postpartum period: relationship to spontaneous abortion. AB - The aim of this study was to determine the prevalence of autoimmune thyroid disease and the risk of miscarriage in autoimmune thyroid antibody (ATA)-positive women. Eight hundred seventy-six subjects completed the study, and 12.3% were thyroid antibody-positive (4.5% tested positive for both thyroid peroxidase antibody [TPO-Ab] and thyroglobulin autoantibody [Tg-Ab], 4.79% were TPO-Ab positive only, and 3.1% were Tg-Ab-positive only). Fifty percent of the ATA positive women and 14.1% of the ATA-negative group had a history of spontaneous abortion. Forty-eight of the ATA-positive women developed postpartum autoimmune thyroid dysfunction (PATD). Of these, 50% had hypothyroidism alone, 31.3% had transient hyperthyroidism followed by hypothyroidism, and 18.8% had transient thyrotoxicosis alone. Of the 48 PATD subjects, 12.5% developed persistent hypothyroidism. None of the ATA-negative women developed any form of thyroid dysfunction. The thyroid-stimulating hormone (TSH) levels in the ATA-positive group were significantly higher than those in the ATA-negative group, and only the ATA-positive women with a history of abortion had significantly higher TSH and lower free thyroxine (FT4) concentrations than the other subgroups. The results revealed a 5.5% prevalence rate for PATD in the study population. In addition to TPO-Ab, Tg-Ab is a useful marker for autoimmune thyroiditis. PMID- 11762716 TI - Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma. AB - Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker. PMID- 11762717 TI - Increasing incidence and characteristics of differentiated thyroid cancer in Huntington, West Virginia. AB - Since 1985, we have observed an increasing number of differentiated thyroid cancer cases in Huntington, West Virginia. We describe tumor incidence, patient and tumor characteristics, treatment modalities, and tumor recurrence and death. One hundred seventeen patients with differentiated thyroid cancer were identified between 1976 and 1999. Data were collected from patient records in our practice and the tumor registries at the three hospitals serving our community. The annual incidence of differentiated thyroid cancer increased significantly from fewer than 3 cases per 100,000 prior to 1996 to 9.4 cases per 100,000 in 1999. The median age at diagnosis was 49 years (range, 16-80). The median tumor size was 2.5 cm (range, 1.2-10). Forty-seven percent of the patients had bilateral disease, 28% had three or more tumors, 44% had thyroid capsular invasion, and 16% had gross extrathyroid invasion at surgery. Twenty-two percent had cervical lymph node involvement and 9% had distant metastases at diagnosis. During 1-month to 23 year follow-up, 11% had recurrence, and 5% died of thyroid cancer. In summary, differentiated thyroid cancer has increased dramatically in our community. The tumors appear to be aggressive at diagnosis as reflected by the high percentage of tumors with bilateral, multicentric, and locally invasive disease. PMID- 11762718 TI - Cystic ovarian metastasis from papillary thyroid carcinoma: a case report. AB - Ovarian metastasis from a primary thyroid carcinoma is rare. In this report we describe a woman who manifested the unusual occurrence of metastases of papillary thyroid carcinoma to the ovary. Both clinically and pathologically, such a presentation can be difficult to distinguish from benign cystic neoplasms of the ovary or cystic struma ovarii. PMID- 11762719 TI - Adrenal metastasis secondary to papillary thyroid carcinoma. AB - Differentiated papillary thyroid carcinoma is usually indolent. Distant metastases from papillary thyroid cancer are rare and associated with poor prognosis. To our knowledge there have been no reported cases of functioning adrenal metastases secondary to papillary carcinoma of the thyroid. Here we report a patient with papillary thyroid carcinoma where surveillance scanning with whole-body 131I scan revealed a large, solitary adrenal metastasis. A 73 year-old woman was treated aggressively for a large papillary thyroid carcinoma. After fine-needle aspiration biopsy of the thyroid nodule, she underwent near total thyroidectomy and postoperative treatment with 150 mCi of 131I. Nine months later, surveillance whole-body 131I scanning revealed a large focus of uptake in the right adrenal gland. The patient underwent adrenalectomy and a papillary thyroid carcinoma metastasis was confirmed. To our knowledge this is the first description of a functioning papillary thyroid carcinoma metastatic to the adrenal. PMID- 11762720 TI - Complete lingual ectopia of the thyroid in a hypothyroid child. PMID- 11762721 TI - Utilization of thyrogen. PMID- 11762722 TI - Thyroid transcription factor-2 gene expression in benign and malignant thyroid lesions. AB - Thyroid transcription factor-2 (TTF-2) is a recently cloned thyroid-specific gene and is central to the development and differentiation of the thyroid follicular cell. Information regarding transcript levels in normal and diseased adult human thyroids is lacking. We have investigated TTF-2 gene expression in various thyroid pathologies and assessed its potential in preoperative diagnosis of thyroid nodular disease, which is a common clinical problem. We have used reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) and detected TTF-2 transcripts in 60% of 125 samples of adult human thyroids tested by RT-PCR (64% of 35) or ISH (59% of 90). In normal thyroid tissues TTF-2 transcript levels are low, 18 of 36 were weakly positive and 18 of 36 negative when tested by ISH. In the benign lesions, TTF-2 transcripts were detected either by RT-PCR or ISH in 8 of 8 Graves disease; 3 of 7 Hashimoto's; 2 of 2 follicular hyperplasia; 15 of 21 follicular adenoma; 11 of 13 multinodular goiters and 0 of 1 hyalinizing trabecular adenoma. In the malignant thyroid lesions, TTF-2 transcripts were detected in 8 of 18 follicular cancers; 0 of 2 anaplastic carcinoma, and 11 of 17 papillary cancers. Compared with normal thyroids, transcripts were more abundant in 24% of thyroid lesions tested by ISH. In conclusion, we report for the first time on TTF-2 gene expression in normal and diseased adult human thyroids. PMID- 11762723 TI - Getting started. PMID- 11762724 TI - Distal radius fractures: therapy practice patterns. AB - Identifying practice patterns for therapy interventions following distal radius fractures (DRFs) is necessary to define the most frequently used examination and intervention techniques. The purpose of this study was to identify preferred practice patterns and physical and functional outcome measures used during DRF management. Two hundred forty-two therapists (PTs, OTs, and CHTs) were surveyed by questionnaire at an annual hand therapy meeting. A descriptive analysis of data was performed. Preferred practice patterns during the immobilization and the post-immobilization periods were identified. More than 75% of the surveyed therapists used upper extremity range-of-motion exercises and compressive wrap with retrograde massage during the immobilization phase. More than 90% of therapists included range-of-motion exercises and heat/cold modalities in the post-immobilization treatment plans. Physical impairment measures of outcome were used much more frequently than functional outcome questionnaires in assessing progress during treatment. This study advances the evidence-based practice of therapy by establishing a foundation for future research. PMID- 11762725 TI - Thenar eminence quantitative sensory testing in the diagnosis of proximal median nerve compression. AB - Diagnosis of proximal median nerve compression (PMNC) remains a clinical challenge. The authors hypothesized that measurement of the sensibility of the thenar eminence might identify PMNC by demonstrating abnormal function in the palmar cutaneous branch of the median nerve. This hypothesis was evaluated by means of quantitative sensory testing of the thenar eminence in 33 healthy volunteers, 14 patients with carpal tunnel syndrome, and 35 patients with PMNC. The cutaneous pressure thresholds for one-point static touch (1PS) and two-point static touch (2PS) were measured with the Pressure-specified Sensory Device (Sensory Management Services, Baltimore, Maryland). There was no significant difference in thenar eminence sensibility between the healthy volunteers and the patients with carpal tunnel syndrome. In contrast, patients with PMNC had higher cutaneous pressure thresholds for 1PS (p<0.001), 2PS-pressure (p<0.001), and 2PS distance (p<0.001) than did patients with carpal tunnel syndrome. The p values were less than 0.001 for each of these three comparisons between the healthy volunteers and the patients with PMNC. For the diagnosis of PMNC, quantitative sensory testing of the thenar eminence has a sensitivity of 90.3%, a specificity of 83.3%, and a positive predictive value of 87.5%. PMID- 11762726 TI - Evaluation of hand sensibility: a review. AB - Many assessment devices and measures have been described to evaluate sensibility, with little consensus on the optimal measurement tool. The purpose of this paper is to review the assessment methods and devices used in the evaluation of hand sensibility. Consideration is given to the characteristics of each measurement tool, the information necessary for complete patient evaluation, and the battery of valid and reliable measurements that provide the most complete and accurate patient assessment. PMID- 11762727 TI - Sensible manual muscle strength testing to evaluate and monitor strength of the intrinsic muscles of the hand: a commentary. AB - Hand therapists often assess, evaluate, and monitor the status of, and changes in the strength of, the intrinsic muscles of the hand. Some common indications are peripheral and central neuropathies and nerve lacerations and repairs. The therapist will often use a muscle chart that lists all the muscles innervated by the ulnar and median nerves, and all muscles will be tested. Not all muscles in the hand can be sufficiently isolated to grade their strength, nor is it always necessary to test all muscles innervated by a particular nerve to evaluate the presence or extent of motor function impairment or monitor changes. This paper discusses the tests by which changes in strength of the ulnar and median innervated intrinsic muscles can be assessed and the reasons that certain muscles cannot or need not be tested. Information about the reliability of muscle testing is also given. PMID- 11762728 TI - Assessing hand grip endurance with repetitive maximal isometric contractions. AB - The purpose of this study was to identify a method for measuring hand grip endurance in patients with hand injury as well as in healthy subjects. Twenty hand-injured patients and 60 healthy subjects participated in the study. Each subject performed two sets of maximal repetitive isometric contractions on the Grippit instrument for 180 seconds, with a contraction time of 2.5 seconds and a rest time of 1 second. Reliability data were high for initial grip force and for absolute and relative endurance values at 90 seconds (r range, 0.73 to 0.97, p < 0.001). Relative endurance at 180 seconds, though, showed weaker reproducibility (r = 0.54, p < 0.01). A measuring period of 90 seconds instead of 180 seconds is suggested, because of the results of test-retest reliability. The method allows endurance to be described in relative force values (as a percentage) as well as in absolute force values (Newtons). PMID- 11762729 TI - The effects of gloves on grip strength and three-point pinch. AB - No-glove, leather-glove, nitrile-glove, and vinyl-glove conditions were evaluated to determine their effects on grip strength and three-point pinch. Forty-one adult volunteers from a local university and local hospital participated in the two-day study. The order of testing was randomly assigned. A hydraulic hand dynamometer and a hydraulic pinch gauge were used to evaluate grip strength and three-point pinch with no glove and with each glove type. Grip strength and three point pinch were tested on separate days. Grip strength test results showed statistically significant differences (p < 0.05) for no glove vs. leather glove, no glove vs. nitrile glove, no glove vs. vinyl glove, leather glove vs. nitrile glove, and leather glove vs. vinyl glove, but no statistically significant difference for nitrile glove vs. vinyl glove. Three-point pinch test results also showed statistically significant differences (p < 0.05) for no glove vs. leather glove, leather glove vs. nitrile glove, and leather glove vs. vinyl glove, but no statistically significant differences for no glove vs. nitrile glove, no glove vs. vinyl glove, and nitrile glove vs. vinyl glove. The results indicate that glove type may have clinical applications for occupational and physical therapists whose patients use gloves in the workplace. PMID- 11762731 TI - A flexion contracture splint for the distal interphalangeal joint: distal interphalangeal joint flexion contracture splinting. PMID- 11762730 TI - The use of manual edema mobilization for the reduction of persistent edema in the upper limb. AB - Management of persistent edema with the common treatment methods reported in the literature is not always successful. Manual edema mobilization (MEM) is a relatively new treatment regimen derived from established European and Australian lymphedema reduction regimens. It includes the use of exercises, light skin tractioning massage techniques following the lymphatic pathways, and the use of low-compression garments. The typical patient who may benefit from the use of MEM has a presumed healthy lymphatic system, is an active participant, and performs some of the techniques independently between therapy sessions. This case report describes the use of MEM on a patient with multiple trauma, which resulted in a significant reduction--78%--of the persistent edema in the affected upper limb. A theoretic rationale is offered for each MEM technique. PMID- 11762732 TI - Likelihood ratios: determining the usefulness of diagnostic tests. PMID- 11762733 TI - Salicylic acid: one more reason to eat your fruits and vegetables. PMID- 11762734 TI - Take 10! Classroom-based program fights obesity by getting kids out of their seats. PMID- 11762735 TI - Becoming a Medicare provider: systems for success. PMID- 11762736 TI - Reductionism and the narrowing nutrition perspective: time for reevaluation and emphasis on food synergy. PMID- 11762737 TI - Saturated fat intake is reduced in patients with ischemic heart disease 1 year after comprehensive counseling but not after brief counseling. AB - OBJECTIVE: To examine the dietary habits of patients with ischemic heart disease 1 year after they received either dietary advice on using the Plate Model and how to increase intakes of fruits and vegetables in a 10-minute session (brief counseling group, BCG) or dietary advice primarily based on the National Cholesterol Education Program Step I diet provided in 2 individually tailored 50 minute sessions held 3 months apart (comprehensive counseling group, CCG). DESIGN: A randomized study that included dietary intake evaluation on basis of 7 day weighed food records completed at 3 occasions: immediately before counseling (week zero), 12 weeks after counseling, and 52 weeks after counseling. SUBJECTS: BCG was composed of 15 men and 2 women and CCG was composed of 16 men and 3 women with ischemic heart disease age 70 years or younger recruited from the Department of Cardiology, Odense University Hospital, Odense, Denmark. STATISTICAL ANALYSES PERFORMED: ANOVA, unpaired t tests, and multiple regression analysis, as well as nonparametric statistical analyses were carried out. RESULTS: The comprehensive counseling resulted in significant improvements from week 0 to 52 in the percent of energy from fat (33% to 28%), saturated fat (12% to 9%) and carbohydrate (51% to 54%) consumed by the subjects. The corresponding values in BCG did not differ significantly (31% to 32%, 11% to 12%, 53% to 52% respectively). Differences from week 0 to 52 between groups were significant for fat, saturated fat, and carbohydrate intake. In CCG, median intakes of fish, fruits, and vegetables were 44 g/day, 172 g/day, and 315 g/day, respectively, at week 52. The corresponding values in BCG were 44 g/day, 129 g/day, and 224 g/day. There was no significant difference either within or between the groups. CONCLUSION: This study suggests that sustained improvements in dietary behavior require individualized and reinforced counseling in patients with ischemic heart disease. Changes in intakes of fish, fruits, and vegetables need to be specifically targeted. PMID- 11762738 TI - Postpartum exercise and food intake: the importance of behavior-specific self efficacy. AB - OBJECTIVE: To examine the relationships between psychosocial characteristics and change in exercise and food intake of women during the first year postpartum. DESIGN: A prospective cohort study following women from pregnancy until 1 year postpartum. Psychosocial variables, change in food intake, and exercise frequency were assessed using anonymous mailed questionnaires during pregnancy and at 1 year postpartum. Sociodemographic and anthropometric information was obtained from the medical record. SUBJECTS/SETTING: Six hundred twenty-two women who enrolled for prenatal care in the Bassett Healthcare system between November 7, 1994, and November 15, 1996, and who met the eligibility criteria. The attrition rate for completing the questionnaire at 1 year postpartum was 20%. STATISTICAL ANALYSES PERFORMED: Multivariate linear regression with exercise frequency at 1 year postpartum and change in food intake during the second 6 months postpartum as the dependent variables and psychosocial factors assessed at 1 year postpartum as the independent variables, controlling for sociodemographic variables, body mass index, and gestational weight gain. RESULTS: Higher exercise self-efficacy and having the intention to exercise were associated with more frequent exercise at 1 year postpartum in the multivariate regression analysis (r2 = 20%). Food intake self-efficacy, body satisfaction, weight gain acceptance, and drive for thinness were all significant in the multivariate analysis (r2 = 7%) and higher scores on these variables were associated with reductions in food intake. APPLICATIONS/CONCLUSIONS: Interventions that aim to help women get regular exercise and make appropriate reductions in food intake during the postpartum period should focus on self-efficacy specific to the targeted behaviors. For example, dietitians may strengthen exercise self-efficacy by providing postpartum women with mastery experiences of setting realistic exercise goals. Likewise, dietitians can focus on food intake self-efficacy by modeling strategies that women can use to avoid overeating in stressful situations. PMID- 11762739 TI - Development and reproducibility of a brief food frequency questionnaire for assessing the fat, fiber, and fruit and vegetable intakes of rural adolescents. AB - OBJECTIVE: To describe the systematic development and reproducibility of a food frequency questionnaire (FFQ) designed to meet the specific research requirements of the Goals for Health cancer prevention intervention program for rural middle school children. DESIGN: A 4-step process was used to develop a brief FFQ for scoring intakes of total fat, fiber, and fruits and vegetables. The resulting questionnaire consisted of 25 food frequency items and 10 supplemental questions. Reproducibility of the questionnaire was determined by comparing responses at the beginning and end of a 4-month interval. SUBJECTS: Study subjects were sixth- and seventh-grade students attending middle schools in rural areas of Virginia and upstate New York. Seventh-grade students participated in the pilot study, and sixth-grade students participated in the reproducibility study. The final version of the FFQ was completed twice by 539 sixth graders. After exclusions for missing and unreliable data, the usable sample size was 415. Boys were somewhat more likely than girls to be excluded for missing data. African-American students comprised 32% of the population. STATISTICAL ANALYSES PERFORMED: Each food frequency item was associated with 3 scores--a fat score, a fiber score, and a combined score for the number of servings of fruits and vegetables. Means and standard deviations were determined for nutrient variables, differences between repeat administrations were tested for significance by paired t test, and Pearson correlation coefficients were calculated for nutrients and for individual food items. RESULTS: Correlation coefficients for nutrient scores were 0.58 for fat, 0.49 for fiber, and 0.51 for fruits and vegetables. For individual food items, correlations ranged from 0.24 to 0.59 (mean=0.41). APPLICATIONS/CONCLUSIONS: Using a systematic approach to developing a study-specific FFQ for rural adolescents is feasible. Further, the reproducibility of the Goals for Health questionnaire was demonstrated for the 3 nutrient scores it was designed to measure. This developmental approach may be readily adapted to other populations, study designs, and nutrients of interest. The validity of the questionnaire remains to be tested. PMID- 11762740 TI - Nutritional supplements used in weight-reduction programs increase intestinal gas in persons who malabsorb lactose. AB - OBJECTIVE: To determine if ingestion of 2 doses of milk-based dietary supplements produce gaseous symptoms in subjects who malabsorb lactose. DESIGN: Randomized, controlled, crossover trial. SUBJECTS/SETTING: Ten community-based subjects who malabsorb lactose. INTERVENTION: Ingestion of 2 standard servings of milk-based supplements (a powder reconstituted in fat-free milk or a ready-to-drink preparation) or low-lactose control preparations. MAIN OUTCOME MEASURES: Frequency of flatus passage and subjective impression of bloating, flatulence, and abdominal discomfort. STATISTICAL ANALYSIS: Wilcoxon signed-rank test. RESULTS: The high lactose content (27 g) of 2 servings of the powder-based supplement ingested without other food resulted in a marked increase in daily flatus passages from the basal level of 9.7+/-8.2 to 30+/-14 (mean+/-SD), and a significant increase in the subjects' perception of gas. In contrast, the lower lactose content (18.4 g) of 2 servings of a ready-to-drink supplement resulted in a flatus frequency of 17+/-10 (P=.14 vs baseline) and no significant increase in the perception of increased gas. Neither supplement resulted in a significant increase in bloating, abdominal pain, or diarrhea. The lactose content of the liquid supplement was reduced by 80% following overnight incubation with an over the-counter lactase preparation. APPLICATIONS/CONCLUSIONS: Persons who malabsorb lactose should be aware that sizable increases in rectal gas commonly occur when milk-based powders reconstituted in milk are used as meal replacements. In contrast, gas problems probably will be minor following ingestion of 2 doses of a ready-to-drink, milk-based supplement. The lactose content of these supplements can be markedly reduced by overnight incubation with over-the-counter lactase preparations, and this manipulation should be beneficial for subjects troubled by the increased gas caused by the consumption of lactose-containing supplements. PMID- 11762741 TI - Perceptions and evaluation of the computerized registration examination for dietitians. AB - In September 1999, the format for the Registration Examination for Dietitians changed from a paper-and-pencil test to a computerized design. The purpose of this study was to determine how examinees reacted to the computerized exam experience. We surveyed 304 registered dietitians in Region VI states who had been eligible as of August 1, 1999, to earn this credential. The response rate was 61% (n=185). Average time between completing the supervised practice program and taking the exam was 5.7 months. Most (n=125) found the computerized format to be satisfactory even though 54.7% reported having anxiety about taking computerized exams. The major difficulties experienced by the examinees were scheduling problems and poor communication on the part of the testing centers. Exam takers need to be better informed about procedural issues, exam center environment, and the limitations of the testing centers. PMID- 11762742 TI - Wheat starch, gliadin, and the gluten-free diet. AB - Individuals with celiac disease generally are advised to follow a lifelong gluten free diet and avoid consumption of the prolamins gliadin (wheat), secalin (rye), and hordein (barley). Although the designation of the diet as glutenfree may imply that the diet contains zero gluten, this is not necessarily true. In some countries (eg, United States, Canada), the gluten-free diet is completely devoid of gluten and is based on foods such as rice and corn that are naturally gluten free. In others (eg, Scandinavia, United Kingdom), the gluten-free diet may include foods such as wheat starch that have been rendered gluten free but nonetheless contain small amounts of toxic prolamins. The discrepancy in the use of foods rendered gluten free exists because the amount of toxic prolamins that individuals with celiac disease may consume without damaging the mucosa of the small intestine is unknown. Minimal research has been conducted on the toxicity of foods rendered gluten free, and there are no definitive data about whether the small amount of prolamin found in these products is safe to consume. Nonetheless, the Codex Alimentarius Standard for gluten-free foods allows a certain amount of prolamin in foods designated gluten free, and these products have been used in many countries for several decades. Well-designed, scientifically sound studies are needed to help determine the amount of toxic prolamins, if any, that may be safely consumed by individuals with celiac disease. Until this research is conducted, dietitians in the United States should continue to advise their patients against the use of wheat starch and other foods rendered gluten free. PMID- 11762743 TI - Impact of a buffet-style dining program on weight and biochemical indicators of nutritional status in nursing home residents: a pilot study. PMID- 11762744 TI - The use of a no-concentrated-sweets diet in the management of type 2 diabetes in nursing homes. PMID- 11762745 TI - Body mass index and effects of refeeding on liver tests in drug-dependent adults in a residential research unit. PMID- 11762746 TI - Research across the curriculum (RAC): integration of research into 3 undergraduate foods courses. PMID- 11762747 TI - Correlates of success on the registered dietetic technician credentialing examination. PMID- 11762748 TI - Case problem: nutrition support in MEN1 syndrome. PMID- 11762749 TI - Bacterial arylsulfate sulfotransferase as a reporter system. AB - To investigate whether the arylsulfate sulfotransferase (ASST) is suitable as a reporter system for monitoring gene expression, a reporter vector carrying the fragments of the astA coding region without the promoter region was constructed and designated as pSY815. As a test of the ASST reporter system's suitability, the regulatory regions of ermC and lacZ were inserted upstream of the coding region of the reporter gene to generate pSY815-EC and pSY815-LZ, respectively. In the absence of the inserted regulatory regions, the plasmids displayed very low background activities in Bacillus subtilis and Escherichia coli. The ASST activity under the control of the ermC regulatory region was increased 4.4-fold in B. subtilis when induced by 0.1 microgml(-1) of erythromycin. These results were consistent with a lacZ reporter gene assay of the ermC regulatory region. Furthermore, we confirmed that the lacZ promoter in E. coli was strongly induced to a 17.9-fold increase by 0.05 mM of isopropyl-beta-D-thiogalactopyranoside (IPTG) in this reporter system. These results indicate that the ASST is a suitable reporter system. The lack of endogenous activity, the simple detection of enzyme activity in the living cell, the commercially available non-toxic substrates, and the high sensitivity make ASST a useful genetic reporter system for monitoring gene expression and understanding gene regulation. PMID- 11762750 TI - Inhibitory role of neutrophils on influenza virus multiplication in the lungs of mice. AB - The protective role of neutrophils on intranasal infection of influenza virus was investigated in 3 strains of tumor-bearing mice with neutrophilic leukocytosis. In vitro multiplication of influenza virus was inhibited by neutrophils from both normal and tumor-bearing mice, and the inhibitory effect of neutrophils was augmented by an addition of fMLP to the culture. Pulmonary virus infectivities in the early phase after infection decreased in such ICR and BALB/c mice, and virus elimination in the late phase was accelerated in the ICR mice. However, no decrease in pulmonary virus infectivity was observed in tumor-bearing C57BL/6 mice. Intranasal administration of fMLP into normal and tumor-bearing C57BL/6 mice after infection significantly inhibited the virus propagation in the lungs. The decrease in neutrophil infiltration into the lung in tumor-bearing C57BL/6 mice was confirmed from histological observations of the lung and lung lavage after infection and from analysis of the neutrophil chemotactic activity induced by fMLP. This might be responsible for the high level of pulmonary virus titer in tumor-bearing C57BL/6 mice. Phagocytic activities of alveolar macrophages and productions of neutralizing antibody were suppressed in the 3 strains of tumor bearing mice. These observations indicated that neutrophils could be significant effector cells as a host defense mechanism against influenza virus infection in vivo, and infiltration and functional activation of neutrophils could play a significant role in virus elimination from the infected site. Furthermore, the inhibition of virus propagation by neutrophils in vitro was almost completely abrogated by an addition of ZnSO4, suggesting that calprotectin could inhibit influenza virus multiplication. PMID- 11762751 TI - Inhibition of p21/Waf1/Cip1/Sdi1 expression by hepatitis C virus core protein. AB - The possibility of interaction between hepatitis C virus (HCV) core protein and the cell cycle regulator protein p21/Waf1/Cip1/Sdi1 (p21/Waf1) in cultured cells was analyzed. Although colocalization of HCV core protein and p21/Waf1 was not clearly observed, p21/Waf1 expression was much weaker in HCV core protein expressing cells than in the control. A Northern blot analysis showed nearly the same level of p21/Waf1 mRNA in both cells, suggesting that HCV core protein inhibited p21/Waf1 expression post-transcriptionally. The degradation patterns of p21/Waf1 did not differ significantly in HCV core protein-expressing cells and in the control, suggesting that the stability of p21/Waf1, once it was accumulated in the cell, was not significantly affected by HCV core protein. But this does not necessarily exclude the possibility that synthesis, maturation, and nuclear transport of p21/Waf1 is impaired, or that the degradation of newly synthesized, improperly processed p21/Waf1 is promoted by HCV core protein. The decrease in p21/Waf1 accumulation was partially inhibited by proteasome inhibitors and a calpain inhibitor in both HCV core protein-expressing cells and the control. In vitro kinase assay revealed that a p21/Waf1-mediated inhibition of cyclin dependent kinase 2 activity was partially negated by HCV core protein. Taken together, the present results suggest that HCV core protein inhibits p21/Waf1 expression post-transcriptionally and impairs the function of p21/Waf1 in the cell. PMID- 11762752 TI - Anti-fibrin antibody binding in valvular vegetations and kidney lesions during experimental endocarditis. AB - In Streptococcus sanguinis (sanguis) induced experimental endocarditis, we sought evidence that the development of aortic valvular vegetation depends on the availability of fibrin. Endocarditis was induced in New Zealand white rabbits by catheter placement into the left ventricle and inoculation of the bacteria. Fibrin was localized in the developing vegetation with 99mTechnetium (Tc)-labeled anti-fibrin antibody one or three days later. When rabbit anti-fibrin antibody was given intravenously on day 1, the mass of aortic valvular vegetation was significantly reduced at day 3; infusion of non-specific rabbit IgG showed no effect. The 99mTc-labeled anti-fibrin antibody also labeled kidneys that showed macroscopic subcapsular hemorrhage. To learn if the deposition of fibrin in the kidneys was a consequence of endocarditis required a comparison of farm-bred and specific pathogen-free rabbits before and after the induction of endocarditis. Before induction, the kidneys of farm-bred rabbits were labeled, but specific pathogen-free rabbits were free of labeling and signs of macroscopic hemorrhage. After 3 days of endocarditis, kidneys of 10 of 14 specific pathogen-free rabbits labeled with 99mTc-labeled anti-fibrin antibody and showed hemorrhage. Kidney lesions were suggested to be a frequent sequellae of S. sanguinis infective endocarditis. For the first time, fibrin was shown to be required for the continued development of aortic valvular vegetations. PMID- 11762753 TI - A mathematical analysis of the interactions between immunogenic tumor cells and cytotoxic T lymphocytes. AB - Recent developments of biotechnology have enabled us to use immunotherapy against certain kinds of tumors in patients. However, it is reasonable to doubt if the immunotherapy can completely aid the rejection of tumors that have escaped from the immune system. In this paper, we propose a new mathematical model of tumor immunity by tumor-specific cytotoxic T lymphocytes (CTLs), since tumor-specific CTLs play an important role in tumor immunity. Using this model, we have mathematically investigated the interactions between immunogenic tumor cells (TCs) and tumor-specific CTLs and evaluated the availability of immunotherapies for tumors. The findings herein demonstrate that three kinds of dynamics of tumor immunity exist: i.e. (1) TCs continue to proliferate with CTLs; (2) TCs are rejected by CTLs; and (3) TCs equilibrate with CTLs, but with little possibility of the equilibrium. The findings also demonstrate that a sufficient increase in CTLs by immunotherapy can aid the rejection of TCs, but an insufficient increase in CTLs by immunotherapy causes only a transient regression of TCs. Clinically the findings mean that increasing tumor-specific CTLs, e.g., by vaccination or adoptive transfer of tumor-specific CTLs expanded ex vivo, can theoretically aid the rejection of TCs. PMID- 11762754 TI - Molecular evolution of human echovirus 9 isolated from patients with aseptic meningitis in northern Kyushu during the summer of 1997. AB - An epidemic of aseptic meningitis caused by human echovirus 9 (E-9) occurred in the summer of 1997 in northern Kyushu, Japan. Sequences of genome position 2504 3358, which encoded a part of VP1, of the nine isolated viruses were determined. An RGD motif and B-C loop were found in all. They were almost identical and closely related to the virulent strain Barty. PMID- 11762755 TI - Characterization of two genes encoding ferritin-like protein in Actinobacillus actinomycetemcomitans. AB - Two genes encoding ferritin-like protein, designated afnA and afnB, were identified in the upstream region of actX on the Actinobacillus actinomycetemcomitans chromosomal DNA. The actX has been reported to be a regulatory gene homologous to the Escherichia coli fnr, which controls the growth and virulence of A. actinomycetemcomitans under anaerobic conditions. The afnB located 340 bp-upstream from the actX, and the afnA located just 15 bp-upstream from afnB. The afnA and afnB encoded 161 and 165 amino acid residues, respectively, which were similar to ferritin-like proteins of other microorganisms. Western immunoblotting using rabbit antiserum against E. coli ferritin showed these two proteins, which are reactive with the serum with 19-kDa molecular masses, are produced from A. actinomycetemcomitans. The N-terminal amino acid sequences of the two proteins were consequent with those deduced from afnA and afnB. Northern hybridization revealed that the afnA and afnB constituted a bicistronic operon and the accumulation of afnA and afnB mRNA was upregulated under aerobic conditions. These findings suggested that the operon was regulated by the presence of oxygen. The two ferritin-like proteins may have important roles in the adaptation of A. actinomycetemcomitans to oxidative environmental changes. PMID- 11762756 TI - Direct extraction of specific pharmacophoric flavonoids from gingko leaves using a molecularly imprinted polymer for quercetin. AB - A new straightforward approach to extract active components from Chinese traditional herb was reported by using a molecularly imprinted polymer (MIP) as the sorbent material. The MIP was prepared using quercetin, a typical active compound of the flavonoid family in gingko leaves as the template. Acrylamide was used as the functional monomer and two polar solvent tetrahydrofuran was used as the porogen. Afterwards, the polymer was evaluated by chromatographic analysis. It exhibited high selectivity for quercetin and good affinity to its structural analogues. Specific binding amount of quercetin on the MIP in the solvent methanol was 12 microg/g polymer by the cartridge test. The MIP cartridge could directly trap a specific class of compounds including quercetin and kaempferol from the hydrolyzate of gingko leaves. The result demonstrated the possibility of direct extraction of certain pharmacophoric constituents from herb by MIP technology. The compounds extracted were confirmed by time-of-flight mass spectrometry. PMID- 11762757 TI - Strategies for in-capillary derivatization of amino acids in capillary electrophoresis using 1,2-naphthoquinone-4-sulfonate as a labeling reagent. AB - This paper examines the potentiality of in-capillary derivatization for improving the sensitivity of the spectrophotometric detection of amino acids in capillary zone electrophoresis. 1,2-Naphthoquinone-4-sulfonate was selected as the labeling agent of amino acids. The underivatized sample and the reagent solution segments are injected by pressure into the capillary prior to applying the running voltage. The corresponding derivatization reaction occurs inside the capillary once the potential is applied, as it induces mixing of the sample with the reagent. Several introduction modes consisting of tandem or sandwich configuration have been evaluated. These techniques result in a straightforward and automated way of carrying out a derivatization. Furthermore, in-capillary procedures may become much more attractive than conventional pre-capillary derivatization in terms of sensitivity and reproducibility. The optimum operation mode found consists of a sandwich system where the sample is injected in between two reagent segments. The method was applied to the determination of amino acids in feed samples. Results show a good concordance with those given by a standard amino acid analyzer. PMID- 11762758 TI - Complex formation analysis of water-soluble calixarenes by capillary zone electrophoresis. AB - The equilibria of complex formation reactions between various kinds of cations and anionic calixarenes in an aqueous solution were analyzed by capillary zone electrophoresis on the basis of the change in electrophoretic mobility of the calixarenes. The apparent electrophoretic mobility of the calixarenes decreased with increasing concentrations of alkali metal ions and quaternary ammonium ions. Equilibrium constants were determined by a non-liner least-squares analysis using the changes in apparent electrophoretic mobility. The complex formation constants obtained with alkali metal ions were in the order of 10(2.3) - 10(3.0), and those with quaternary ammonium ions were 10(2.9) - 10(4.2), providing less selectivity among them. The selectivity of the calixarene toward alkali metal and quaternary ammonium ions in aqueous solution involves flexible structure, and compensative interactions of electrostatic and hydrophobic interactions. From the results obtained in this work, the electrophoretic method has proved to be useful for analyzing the reactivity of anionic calixarene in aqueous solution. PMID- 11762759 TI - Towards functional group-specific detection in high-performance liquid chromatography using mid-infrared quantum cascade lasers. AB - A distributed feedback quantum cascade laser was applied for the first time as a powerful light source for mid-infrared (MIR) detection in liquid chromatography. Fructose and glucose in red wine were separated with an isocratic HPLC system, which was connected to a custom-made flow cell. This flow cell was constructed of two diamond windows with adjustable spacing and two hollow wave-guides for guiding the incoming and outgoing light. The HPLC column based on an ion-exchange resin with calcium(II) counter ion was run at 80 degrees C with 0.04% formic acid as the mobile phase. Under these conditions the carbohydrates could not be completely separated from the organic acids also present in wine. However, the emission of the laser at 1067 cm(-1) matches the absorption maximum of fructose and glucose, whereas the organic acids do not absorb appreciably at this wavenumber. Thus group-specific detection could be achieved. Additionally, the optical path length could be increased from 25 to 125 microm, which is very promising in gaining enhanced sensitivity compared to Fourier transform IR detection. PMID- 11762760 TI - Determination of low thiourea concentrations in industrial process water and natural samples using reversed-phase high-performance liquid chromatography. AB - A rapid LC method was developed to determine thiourea in natural samples and freshly prepared as well as used tin-baths from the galvanic industry, with LC on a C18-bonded silica column and with doubly distilled water as eluent. The retention time of thiourea is 1.35 min +/- 5%. UV detection is at 236 nm. Small sample volumes of 10-50 microl allow detection down to 2 microg/l thiourea without any interference by heavy metals or organic compounds and in the case of marine samples by mineral salts. The presented technique should be highly useful for industrial purposes. PMID- 11762761 TI - Numerical estimation of multicomponent adsorption isotherms in preparative chromatography: implications of experimental error. AB - Since experimental methods for measuring multicomponent adsorption isotherms are extremely tedious, numerical approaches are an attractive alternative. Here, the variance in isotherm parameters as a function of experimental error in measured effluent concentrations is quantified. The number of experimental replicates needed to obtain isotherm parameters to a desired level of accuracy is calculated explicitly. After the covariance matrix of the parameters has been determined, Monte Carlo methods are found to be rapid and effective. The use of different kinds of experiments, the effect of resolution and loading, and the impact of the number of measured data points are described. PMID- 11762762 TI - Flux of gases across the air-water interface studied by reversed-flow gas chromatography. AB - In the present work the reversed-flow gas chromatographic technique was applied for the study of flux of gases across the air-water interface. The model system was vinyl chloride-water, which is of great significance in food and environmental chemistry. Using suitable mathematical analysis, equations were derived by means of which the following physicochemical quantities were calculated: diffusion coefficient of vinyl chloride (VC) into water, partition coefficient of VC between the water (at the interface and the bulk) and the carrier gas nitrogen, overall mass transfer coefficients of VC in the gas (nitrogen) and the liquid (water), gas and liquid film transfer coefficients of VC, gas and liquid phase resistances for the transfer of VC into the water, and finally the thickness of the stagnant film in the liquid phase, according to the two-film theory of Whitman. From the variation of the above parameters with temperature, as well as the volume and the free surface area of the water, useful conclusions concerning the mechanism for the transfer of VC into water were extracted. These are discussed in comparison with the same parameters calculated from empirical equations or determined experimentally by other techniques. PMID- 11762763 TI - Solid-phase microextraction of monocyclic aromatic amines using novel fibers coated with crown ether. AB - Three solid-phase microextraction (SPME) fibers prepared by the sol-gel method, containing hydroxydibenzo-14-crown-4 (OH-DB14C4), dihydroxy-substituted saturated urushiol crown ether (DHSU14C4) and 3,5-dibutyl-unsymmetry-dibenzo-14-crown-4 dihydroxy crown ether (DBUD14C4), respectively, were evaluated for the determination of aromatic amine (aniline, m-toluidine, N,N-diethylaniline, N ethyl-m-toluidine, 3,4-dimethylaniline). The sol-gel-derived hydroxy-dibenzo14 crown-4-coated fiber has the best affinity for several aniline derivatives. Optimization was carried out for the determination of aromatic amines with SPME fibers. The linearity was from 0.11 to 29 microg/ml and detection limits varied from 0.17 to 0.98 ng/ml. Relative standard deviation (n=5) was found to be 3.23 6.20%. The coating proved to be very stable at high temperature (to 340 degrees C) and in different solvents (organic and inorganic). The method was applied to the determination of aromatic amines in wastewater samples from a pharmaceutical factory. PMID- 11762764 TI - Tris(2,2'-bipyridyl)ruthenium(III)-based electrochemiluminescence detector with indium/tin oxide working electrode for capillary electrophoresis. AB - A novel tris(2,2'-bipyridyl)ruthenium(III) [Ru(bpy)3(3+)]-based electrochemiluminescence (ECL) detector for capillary electrophoresis (CE) has been developed. The detector was of the wall-jet configuration and an indium/tin oxide (ITO)-coated glass plate was used as the working electrode for end-column detection. Potential control of the ITO electrode was provided using a DC battery, without decoupling the detector from the CE field. Electrochemical behavior of Ru(bpy)3(2+) at the ITO electrode was found to be analogous to that at a Pt electrode. In the presence of tertiary or some secondary amines, ECL emission due to reaction between in situ generated Ru(bpy)3(3+) and analytes can be observed at the ITO surface. With 15 mM sodium borate (pH 9.5) plus 1 mM Ru(bpy)3(2+) present in the detection cell and the ITO electrode biased at 1.5 V (vs. Pt wire reference), a detection limit of 1 microM proline with a theoretical plate number of 4000 was obtained using the developed CE-ECL detection system. The detector response was found to be analyte-dependent, e.g. tryptophan gives no response, and the response for histidine is about 13-fold lower than that of proline. PMID- 11762765 TI - Capillary electrophoretic determination of sulfite using the zone-passing technique of in-capillary derivatization. AB - A new capillary electrophoretic (CE) method was developed for the simple and selective determination of sulfite. The proposed method is based on the in capillary derivatization of sulfite with iodine using the zone-passing technique and direct UV detection of iodide formed. The optimal conditions for the separation and derivatization reaction were established by varying concentration of iodine, electrolyte pH and applied voltage. The optimised separations were carried out in 20 mmol l(-1) Tris-HCl electrolyte (pH 8.5) using direct UV detection at 214 nm. Experimental results showed that the injection of the iodine zone from anodic end of the capillary gives significantly better precision. Common UV absorbing anions such as Br-, l-, S2O3(2-), NO3-, NO2-, SCN- did not give any interferences. Valid calibration (r2=0.998) is demonstrated in the range 1 x 10(-5) - 8 x 10(-4) mol l(-1) of sulfite. The detection limit (SIN=3) was 2 x 10(-6) mol l(-1). The proposed system was applied to the determination of free sulfite in wines. The recovery tests established for wine samples were within the range 92-103%. The CE results were compared with those obtained by iodometric titration technique. PMID- 11762766 TI - On-line capillary electrophoresis with mass spectrometry detection for the analysis of carbohydrates after derivatization with 8-aminonaphthalene-1,3,6 trisulfonic acid. AB - Capillary electrophoresis (CE) with mass spectrometry (MS) detection is an ideal tool for analytical use, which combines a nano quantity assay with mass determination. Carbohydrate analysis has always been a challenge because of the inherent structural complexity and the lack of a chromophore, unless derivatization is used. Here we use the derivatization of carbohydrates with a fluorophore, 8-aminonaphthalene-1,3,6-trisulfonic acid (ANTS). This chromophore has two advantages, first, it facilitates UV and fluorescence detection and, second, it introduces negative charge to the analyte, which enhances zone electrophoretic separation. In this study, CE combined with negative ion electrospray MS (ESI-MS) was evaluated for the on-line analysis of ANTS labeled carbohydrates and cellulose fragments. The CE system was connected to the MS by a sheath-liquid electrospray arrangement. The ANTS reagent and Dextrin-15, which contains oligomers of maltose, were used as model samples for ESI-MS optimization in flow-injection-MS and CE-MS modes, respectively. Various sheath-liquid compositions regarding organic modifier (isopropanol, methanol, or acetonitrile) and electrolyte (acetic acid-formic acid, ammonium acetate, or triethylamine) were studied. The response as well as the analyte charge state distribution was found to be dependent on the composition and the orifice voltage. Low-pH conditions with isopropanol as organic modifier were sensitive, stable, and the most favorable for analysis. PMID- 11762767 TI - Effect of a soluble ionic polymer on the separation of anions by capillary electrophoresis. AB - A silica capillary for CE analysis of anions can be conditioned with NaOH, rinsed with water, coated with a cationic polymer, and equilibrated with the background electrolyte in only 2 min for each of the four steps. The coated surface has a positive charge that gives a substantial anodic electroosmotic flow (EOF) over the range of pH 2.5-12.0. The migration times of sample anions and a neutral marker (used for EOF calculations) are generally reproducible to an RSD of 1% or better, both for successive runs on a single capillary and from capillary to capillary. It was shown that the type of buffer used affects the EOF of a coated capillary. A concentration of 100 mM or higher sodium chloride minimizes differences in EOF with different buffers and also gives sharper peaks for sample anions. PMID- 11762768 TI - Separation and determination of n-alkylamines and histamine by capillary zone electrophoresis using salicylaldehyde-5-sulfonate as a derivatizing reagent. AB - Sodium salicylaldehyde-5-sulfonate (SAS) was investigated as a derivatizing reagent for the separation and determination of primary amines by capillary zone electrophoresis (CZE). The amines were derivatized with SAS to the corresponding Schiff bases before their determination. Optimal conditions for the formation reactions of the Schiff bases and the CZE analysis were investigated in details. The Schiff bases were formed almost completely within 9 min in 40%(v/v) ethanol solution at 40 degrrees C. A migrating solution containing 40%(v/v) ethanol and 20 mM phosphate buffer (pH 7.8) was found to be preferable for the stability of the Schiff bases. Eight kinds of n-alkylamines were derivatized with SAS under the optimal conditions and the derivatives were successfully separated by a CZE analysis. The proposed method allows simultaneous, sensitive and sufficiently precise determination of the n-alkylamines with the alkyl chain length from 3 to 12 of methylene groups. The derivatization process with SAS was successfully applied to the detection of histamine at a very low level. The detection limit was 2.5-10(-6) M, and it was improved in the order of 8 times compared with the CZE analysis without derivatization. PMID- 11762769 TI - Consensus statement on children at high altitude. PMID- 11762770 TI - Chromatographic procedures for the isolation of plant steroids. AB - In this review, we consider the general principles and specific methods for the purification of different classes of phytosteroids which have been isolated from plant sources: brassinosteroids, bufadienolides, cardenolides, cucurbitacins, ecdysteroids, steroidal saponins, steroidal alkaloids, vertebrate-type steroids and withanolides. For each class we give a brief summary of the characteristic structural features, their distribution in the plant world and their biological effects and applications. Most classes are associated with one or a few plant families, e.g., the withanolides with the Solanaceae, but others, e.g., the saponins, are very widespread. Where a compound class has been extensively studied, a large number of analogues are present across a range of species. We discuss the general principles for the isolation of plant steroids. The predominant methods for isolation are solvent extraction/partition followed by column chromatography and thin-layer chromatography/HPLC. PMID- 11762771 TI - Analysis of steroidal lipids by gas and liquid chromatography. AB - This article describes the most commonly used procedures and recent laboratory methodologies using gas and liquid chromatography developed for separation and quantitation of non-saponifiable steroidal lipids from clinical (human) studies, edible fats and oils or fatty foods. PMID- 11762772 TI - Qualitative and quantitative liquid chromatographic determination of natural retinoids in biological samples. AB - Liquid chromatography continues to be the preferred method for determining retinoids in biological samples. The highly unstable nature of retinoids and the real possibility of artifacts or erroneous results have led to the development of rapid and highly automated protocols for retinoid extraction, separation and detection. Due to strong light absorbance in the ultraviolet region, UV detectors still predominate although mass spectrometric detection is gaining increased popularity. This paper reviews recent advances and provides major guidelines for using liquid chromatography to identify and quantify retinoids in biological samples. PMID- 11762773 TI - Gas chromatography and high-performance liquid chromatography of natural steroids. AB - This review article underlines the importance of gas chromatography (GC), high performance liquid chromatography (HPLC) and their hyphenated techniques using mass spectrometry (MS) for the determination of natural steroids, especially in human biological fluids. Steroids are divided into eight categories based on their structures and functions, and recent references using the above methodologies for the analysis of these steroids are cited. GC and GC-MS are commonly used for the determination of volatile steroids. Although HPLC is a widely used analytical method for the determination of steroids including the conjugated type in biological fluids, LC-MS is considered to be the most promising one for this purpose because of its sensitivity, specificity and versatility. PMID- 11762774 TI - Chromatographic analysis of plant sterols in foods and vegetable oils. AB - This paper reviews recently published chromatographic methods for the analysis of plant sterols in various sample matrices with emphasis on vegetable oils. An overview of structural complexities and biological/nutritional aspects including hypocholesterolemic activities of phytosterols is provided in the Section 1. The principal themes of the review highlight the development and application of chromatographic techniques for the isolation, purification, separation and detection of the title compounds. Pertinent gas chromatographic and high performance liquid chromatographic methods from the literature are tabulated to illustrate common trends and methodological variability. The review also covers specific analyses of natural/synthetic standard mixtures to shed light on potential applicability in plant sample assays. Examples of combined chromatographic techniques linked in tandem for the analysis of complex samples are included. Elution characteristics of sterol components are discussed in the context of analyte substituent effects, structural factors and stationary/mobile phase considerations. PMID- 11762775 TI - Plasma non-cholesterol sterols. AB - Increased levels of plasma sterols other than cholesterol can serve as markers for abnormalities in lipid metabolism associated with clinical disease. Premature atherosclerosis and xanthomatosis occur in two rare lipid storage diseases, Cerebrotendinous xanthomatosis (CTX) and sitosterolemia. In CTX, cholestanol is present in all tissues. In sitosterolemia, dietary campesterol and sitosterol accumulate in plasma and red blood cells. Plasma accumulation of oxo-sterols is associated with inhibition of bile acid synthesis and other abnormalities in plasma lipid metabolism. Inhibition of cholesterol biosynthesis is associated with plasma appearance of precursor sterols. The increases in non-cholesterol sterols, while highly significant, represent only minor changes in plasma sterols, which require capillary gas-liquid chromatography and MS for effective detection, identification and quantification. PMID- 11762776 TI - Analysis of free and esterified sterols in fats and oils by flash chromatography, gas chromatography and electrospray tandem mass spectrometry. AB - A method for the analysis of free and esterified sterols has been developed. Fat or oil samples were separated on solid-phase extraction silica gel columns into a sterol ester fraction, a fraction of triacylglycerols, and a free sterol fraction containing partial acylglycerols and residual triacylglycerols. Sterol esters and acylglycerols of the free sterol fraction were transesterified to methyl esters. The fatty acid methyl esters from sterol ester fraction and the free sterols from sterol ester fraction and free sterol fraction were determined by GLC. Precursor ion electrospray MS-MS of sterol fragment ions of sterol ester fractions were recorded and used for determination of sterol ester proportions in butterfat and vegetable oil samples. PMID- 11762777 TI - Liquid chromatography-UV determination and liquid chromatography-atmospheric pressure chemical ionization mass spectrometric characterization of sitosterol and stigmasterol in soybean oil. AB - A narrow-bore HPLC-UV method was developed for the analysis of two of the more abundant naturally occurring phytosterols in vegetable oils: sitosterol and stigmasterol. The method enabled detection of the compounds at a concentration of 0.42 microg/ml and quantitation at concentrations of 0.52 and 0.54 microg/ml for sitosterol and stigmasterol, respectively. An excellent linearity was determined over two orders of concentration magnitude (r2 0.999-1.000) and verified by applying the Mandel fitting test (p>0.099) and the lack-of-fit test (p>0.057) performed at the 95% confidence level. A good intra-day precision ranging from 0.15 to 1.16% was calculated at two concentration levels (2 and 100 microg/ml). The inter-day reproducibility was verified on 3 different days by performing an homoscedasticity test and analysis of variance. A solid-phase extraction method was developed on silica cartridges for the isolation of phytosterols from soybean oil providing recovery values of 101+/-9 and 106+/-7% for sitosterol and stigmasterol, respectively. Good accuracy of the method was statistically demonstrated since no matrix effect was found for both the analytes. The developed method was applied to the quantitative assay of phytosterols in a soybean oil sample (61+/-5 mg/100 g of stigmasterol and 118+/-4 mg/100 g sitosterol). The HPLC-atmospheric pressure chemical ionization MS technique enabled the identification of stigmasterol, sitosterol and campesterol in the oil sample. PMID- 11762778 TI - Quantitative analysis of desmosterol, cholesterol and cholesterol sulfate in semen by high-performance liquid chromatography. AB - A simple, rapid and accurate method to separate and quantify cholesterol, desmosterol and cholesterol sulfate in human spermatozoa and seminal plasma (SP) is described. This high-performance liquid chromatographic procedure is based on reversed-phase chromatography on a Inertsil ODS2 5 microm silica column with a binary gradient of mixtures of chloroform-methanol and chloroform-methanol-water as the mobile phase at a flow-rate of 0.25 ml/min. Sterols are separated with good resolution and high reproducibility. The eluted sterols are quantified using a light-scattering (mass) detector. As little as 64, 64 and 68 pmol of cholesterol, desmosterol and cholesterol sulfate, respectively, can be quantified under these conditions. Cholesterol is the predominant sterol both in spermatozoa (107+/-7 nmol/10(8) spermatozoa) and SP (0.83+/-0.10 micromol/ml) whereas the concentrations of desmosterol were 38+/-6 nmol/10(8) in spermatozoa and 0.18+/ 0.02 micromol/ml in SP. Cholesterol sulfate represents about 6% of total cholesterol in the spermatozoa and SP. In conclusion, this method offers interesting perspectives for the quantitative analysis of these sterols not only in semen, but also in other biological samples. PMID- 11762779 TI - Steroid analysis for medical diagnosis. AB - Steroid assays are important for medical diagnosis of diseases related to steroid disturbances and abuse. This article reviews the recent progress in analytical methods for steroids in the clinical laboratory. The requirements for these methods are rapid, highly sensitive, specific, direct assay of conjugated steroids, the simultaneous analysis, identification of unknown steroids, and ultra-miniaturization of the separation system. PMID- 11762780 TI - High-performance liquid chromatographic analysis of dehydroepiandrosterone. AB - Qualitative and quantitative analysis of dehydroepiandrosterone and its conjugates in biological matrices and establishment of their relationships with physiological functions is a very active field. This review article discusses methods of separation and quantification of dehydroepiandrosterone and its conjugates using high-performance liquid chromatographic techniques. PMID- 11762781 TI - 7-Hydroxydehydroepiandrosterone epimers in human serum and saliva. Comparison of gas chromatography-mass spectrometry and radioimmunoassay. AB - Recent reports demonstrated that 7-hydroxylated metabolites of dehydroepiandrosterone (DHEA) possess immunomodulatory and antiglucocorticoid properties. Increased 7alpha-OH-DHEA levels were found in patients with Alzheimer's disease. Hence, measurement of steroids in patients with autoimmune diseases or disturbances in the central nervous system could be of interest. A new sensitive GC-MS method for the determination of 7 hydroxydehydroepiandrosterone epimers was developed and compared with previously developed radioimmunoassays. Besides serum, these steroids were, for the first time, measured in saliva where their concentrations were about five times lower. 7alpha- and 7beta-epimer levels correlated well in both body fluids and they were larger in male. PMID- 11762782 TI - Extraction of fat-soluble vitamins. AB - An overview of the different extraction procedures of fat-soluble vitamins from human fluids, foods and pharmaceutical preparations is presented. Methods using organic solvent extraction (both liquid-liquid and solid-liquid extraction), supercritical fluid extraction and solid-phase extraction for the different types of both vitamins and matrices are discussed. PMID- 11762783 TI - Identification and quantitative analysis of the phytoecdysteroids in Silene species (Caryophyllaceae) by high-performance liquid chromatography. Novel ecdysteroids from S. pseudotites. AB - Many species in the genus Silene (Caryophyllaceae) have previously been shown to contain ecdysteroids and this genus is recognised as a good source of novel ecdysteroid analogues. We have used ecdysteroid-specific radioimmunoassays and the microplate-based Drosophila melanogaster B(II) cell bioassay for ecdysteroid agonist and antagonist activities to identify further phytoecdysteroid-containing species in this genus. The main ecdysteroid components from 10 Silene species (S. antirrhina, S. chlorifolia, S. cretica, S. disticha, S. echinata, S. italica, S. portensis, S. pseudotites, S. radicosa, S. regia) were isolated and identified, mainly by normal-phase and reversed-phase high-performance liquid chromatography. The amount of each ecdysteroid was determined by comparing chromatogram peak areas with those for reference 20-hydroxyecdysone (20E) on reversed-phase HPLC. 20E is the most abundant ecdysteroid in each of the Silene extracts. Polypodine B, 2-deoxy-20-hydroxyecdysone and ecdysone are also common ecdysteroids in these Silene species, but the proportions of these ecdysteroids vary between the Silene species. HPLC proved to be a quick and effective way to screen Silene species, determine ecdysteroid profiles and, hence, identify extracts containing novel analogues. An extract of the aerial parts of S. pseudotites was found to contain several new ecdysteroids. These have been isolated and identified spectroscopically (by NMR and mass spectrometry) as 2-deoxyecdysone 22beta-D glucoside, 2-deoxy-20,26-dihydroxyecdysone and 2-deoxypolypodine B 3beta-D glucoside. Additionally, (5alpha-H)-2-deoxyintegristerone A (5alpha-2H 91%, 5alpha-1H 9%) was isolated as an artefact. This study contributes to the understanding of ecdysteroid distribution in Silene species and provides further information on the chemotaxonomic significance of ecdysteroids in Silene species. PMID- 11762784 TI - Chromatographic analysis of Fritillaria isosteroidal alkaloids, the active ingredients of Beimu, the antitussive traditional Chinese medicinal herb. AB - Bulbus Fritillariae derived from plants of various Fritillaria species is the most commonly used antitussive traditional Chinese medicinal herb and is called Beimu. Herbs derived from similar and/or different species of Fritillaria are also used in Japan and Turkey as traditional or folk medicines. Isosteroidal alkaloids are the main bioactive ingredients in Fritillaria species. As the contents and structure types of these bioactive alkaloids vary in different Fritillaria species, quality control of these active principles in herbal Beimu is very important to ensure its safe and effective clinical use. This review describes the development of chromatographic analyses for the simultaneous qualitative and quantitative determination of the main bioactive Fritillaria isosteroidal alkaloids in herbal and biological samples. The recently developed direct HPLC-evaporative light scattering detection method is the most simple, selective and sensitive assay, and is readily used as a suitable quality control method for the analysis of the active principles of herbal Beimu. PMID- 11762785 TI - Chromatographic analysis of alpha-tocopherol and related compounds in various matrices. AB - Tocopherols and tocotrienols (Vitamin E) are part of a group of "minor components" of main interest, present in the unsaponifiable fraction of many samples. Their importance in biological, metabolical and nutritional studies makes determination of tocopherols and related compounds of major interest. Present work critically reviews the different ways to perform sample pre treatment and analysis of these compounds, related to the matrices, other analytes to be measured, sensitivity, and simplicity. The review includes well referenced tables that provide in-depth summaries of methodology for the chromatographic analysis of alpha-tocopherol and related compounds in foods, pharmaceuticals, plants, animal tissues and other matrices. PMID- 11762786 TI - Chromatographic separation of tocopherols. AB - alpha-, beta-, gamma-, and delta-Tocopherols were separated by reversed-phase high-performance thin-layer chromatography (C18RP-HPTLC), normal-phase high performance liquid chromatography (NP-HPLC), reversed-phase high-performance liquid chromatography (C18RP-HPLC), and gas chromatography (GC). The selected topological indices based on connectivity (M, 1chi(v)), on distance matrix (W, (o)B, MTI) and on information theory (I(AC), I(AC)) were calculated for these tocopherols. The observed chromatographic separations of investigated tocopherols were compared. This comparison indicated that the C18RP-HPTLC, NP-HPLC, and GC are the best techniques for the separation of these tocopherols. Topological index (o)B was the most significant. We obtained definite dependence between the numerical values of topological index (o)B and the chromatographic separation of the investigated tocopherols. PMID- 11762787 TI - Analysis of vitamin E isomers in seeds and nuts with and without coupled hydrolysis by liquid chromatography and coulometric detection. AB - A method is described for the determination of vitamin E isomers [alpha-, (beta+gamma)- and delta-tocopherols] in seeds and nuts by reversed-phase HPLC with coulometric detection. Three methods of sample treatment were compared. The first method included alkaline hydrolysis, extraction of analytes from unsaponifiable and injection into the chromatographic system. In the second method, alkaline hydrolysis and later continuous membrane extraction of isomers were coupled with the HPLC system. The third method involved direct extraction of the analytes through a silicone membrane coupled on-line with the chromatographic system. The three methodologies used for the determination of vitamin E isomers in these samples afforded good results for alpha-tocopherol. However for (beta+gamma)- and delta-tocopherols the best results were obtained with the third method. The method without hydrolysis was the simplest one to carry out and analysis took no longer than 40 min from weighing of the samples. Accordingly, it is the method proposed. PMID- 11762788 TI - Liquid chromatographic method for the analysis of tocopherols in malt sprouts with supercritical fluid extraction. AB - A simple, specific and sensitive high-performance liquid chromatographic method has been developed for the determination of tocopherols in malt sprouts. A supercritical fluid extraction (SFE) procedure was used to isolate tocopherols from the vegetal matrix before quantitative analysis. The analytes were separated on a Zorbax reversed-phase column using methanol-water as mobile phase and quantified by measuring its fluorescence at lambda(em)=328 nm after excitation of the analytes at lambda(exc)=303 nm. The limits of detection for alpha-, gamma- and delta-tocopherols were 0.04, 0.05, and 0.05 microg/ml, respectively. The calibration graphs of the method were linear from 0.1 to 1.5, 0.2 to 2.5, and 0.2 to 2.0 microg/ml, for alpha-, gamma- and delta-tocopherols, respectively. This SFE and HPLC procedure is simple, precise and accurate for the determination of tocopherols in malt sprouts. PMID- 11762789 TI - Sensitive analysis of 1alpha,25-dihydroxyvitamin D3 in biological fluids by liquid chromatography-tandem mass spectrometry. AB - A liquid chromatographic-tandem mass spectrometric assay using 5% bovine serum albumin as the calibration matrix has been developed for the quantitative analysis of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] in biological fluids. The analyte was extracted from the matrix after protein precipitation using an automated solid-phase extraction procedure involving both a reversed phase and normal-phase procedure on a single C18 cartridge. The analytical chromatography was performed using a Symmetry C8 50 x 2.1 mm, 3.5 microm column. The mobile phase was a linear gradient from 75 to 99% methanol with a constant concentration of 2 mM ammonium acetate. 1alpha,25(OH)2D3 and the internal standard [2H6]1alpha,25(OH)2D3 were detected by using MS-MS. The ion source was operated in the positive electrospray ionisation mode. The assay is specific, sensitive, and has a capacity of more than 100 samples per day, with a limit of quantitation of 20 pg ml(-1) for a 1.0-ml sample aliquot. The assay has been used for the analysis of 1alpha,25(OH)2D3 in serum from rats and pigs simultaneously with the analysis of the vitamin D analog seocalcitol. PMID- 11762790 TI - A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria. AB - For many years, urine alkalinization has been one of the cornerstones in the treatment of homozygous cystinuria. Because of the relationship found between the excretion of urinary sodium and cystine, potassium citrate has emerged as the preferred sodium-free alkalizing agent. To evaluate the usefulness of potassium citrate for urine alkalization in cystinuric patients, sodium bicarbonate and potassium citrate were compared in 14 patients (10 on tiopronin treatment and four without treatment with sulfhydryl compounds). The study started with 1 week without the use of any alkalizing agents (Period 0) followed by 2 weeks with sodium bicarbonate (Period 1) and 2 weeks with potassium citrate (Period 2). Urinary pH, volume, excretion of sodium, potassium, citrate and free cystine, as well as the plasma potassium concentration, were recorded. Potassium citrate was shown to be effective as an alkalizing agent and, in this respect, not significantly different from sodium bicarbonate. Even though a normal diet was used, a significant increase in urinary sodium excretion was observed with sodium bicarbonate (Period 1). Urinary potassium and citrate excretion increased with potassium citrate (Period 2). A significant correlation was found between urinary sodium and cystine in the tio-pronin-treated patients. No significant differences in cystine excretion were recorded in Periods 0, 1 and 2. Plasma potassium was significantly higher during Period 2, but only one patient developed a mild hyperkalemia (5.0 mmol/l). The use of potassium citrate for urine alkalization in homozygous cystinuria is effective and can be recommended in the absence of severe renal impairment. PMID- 11762791 TI - Cystine analyses of separate day and night urine as a basis for the management of patients with homozygous cystinuria. AB - Based on previous observations of the diurnal variation of urinary cystine excretion, the use of separate day and night urine collections was proposed. To improve the medical treatment of patients with cystinuria, this strategy was performed to guide the fluid intake and the administration of SH compounds (tiopronin, D-penicillamine, and MESNA).Twenty-six patients (19 treated with SH compounds and seven with alkalinization and hydration only) were followed during two 3.5-year periods. During Period 1, 24-h urine was collected and during Period 2, separate day and night urine was collected. There were 56 episodes of high urinary cystine supersaturation (> 1,200 micromol/l) during Period 2, 47% of which would have evaded detection with 24-h urine analysis. In comparison with Period 1, the urinary cystine concentration was lower (P < 0.05), and the urinary volume was higher (P < 0.05) during Period 2. Patients treated with tiopronin had reduced cystine excretion (P < 0.05) and at the end of Period 2, an increased dose of tiopronin, reflecting a more aggressive treatment. Furthermore, a reduced number of stone episodes and need of active stone removal (P < 0.05) was noted in the whole group of patients. Analyses of separate day and night urine samples can be used advantageously to reveal episodes of high supersaturation with cystine not detected in 24-h urine samples. Such a procedure might be useful for optimizing the treatment of patients with cystinuria. PMID- 11762792 TI - The effect of estrogen-replacement therapy on clitoral-cavernosal tissue in oophorectomized rats: a histo-quantitative study by image analyzer. AB - Sexual dysfunction is an important problem for aging females. However, little attention has been paid to female sexual dysfunction. The clitoris is an important organ for physiological sexual function in females. There is a close relationship between the presence of sexual complaints and levels of estrogen. Using the rat as an experimental model, we evaluated the effect of estrogen replacement therapy and its timing on clitoral-cavernosal collogen fiber content after oophorectomy. Four-month-old female Wistar rats (n = 36) weighing 230-250 g were used. They were categorized into four groups: oophorectomized (Group 1: n = 10); oophorectomized delayed estrogen replacement (group 2: n = 10); oophorectomized + immediate estrogen replacement (group 3: n = 10); and sham operated (group 4: n = 6). The estrogen replacement used was 17-beta-estradiol. All rats were euthanized at the same age. The specimens were stained with Masson's trichome technique, and computerized image analysis was used to quantify the collagen-fiber content of clitoral-cavernous tissue. The clitoral collagen fiber percentages in the different groups were as follows: group 1: 64.17 +/- 5.01%; group 2: 62.57 +/- 5.37%; group 3: 56.33 +/- 3.85%; group 4: 51.48 +/- 6.37%, respectively. Although there was a tendency in the untreated group for a higher collagen-fiber content, no statistically significant difference was found among groups (P > 0.05). Although the results of this study were not statistically significant, estrogen did appear to decrease clitoral-cavernosal collagen-fiber content. These findings may be important in the pathophysiology of postmenopausal female sexual dysfunction. PMID- 11762793 TI - Interleukin-1beta gene and receptor antagonist gene polymorphisms in patients with calcium oxalate stones. AB - Interleukin-1 (IL-1) might play a role in the process of bone loss and hypercalciuria and is therefore considered to be involved in the formation of urinary stones. The aim of this study is to test whether the IL-1beta promoter region, exon 5 region and IL-1 receptor antagonist gene intron 2 polymorphisms could be genetic markers for the susceptibility to the formation of urinary stones. A control group of 152 healthy people and a group of 105 patients with recurrent calcium oxalate stone were examined in this study. Polymerase chain reaction (PCR) analyzed the variable number tandem repeats at intron 2 of the IL 1Ra gene for the polymorphisms. PCR-based restriction analysis was done for the IL-1beta gene polymorphisms of the promoter region and exon 5 by the endonucleases Ava I and Taq I, respectively. The polymorphisms studied in the IL 1beta genes did not reveal a strong association with calcium oxalate stone disease when compared with the control group (promoter region by chi-square test, P=0.627: exon 5 region by Fisher's exact test, P = 0.403). Only two frequent alleles of the IL-1Ra gene corresponding to one and two copies of an 86-bp sequence repeat were identified by PCR. The result revealed significant differences between control individuals and stone patients (P < 0.01. Fisher's exact test). In addition, the frequency of the type I allele in the stone group (99.0%) was higher than in the control group (94.0%). The odds ratio for the type I allele of the IL-1Ra gene in calcium oxalate stone disease is 6.041 (95% CI: 1.683 approximately 21.687). There is an association between urolithiasis and polymorphism in the IL-1Ra gene. No significant difference was found when dividing the stone patients into groups with normocalciuria and hypercalciuria in relation to these genetic polymorphisms. Further studies of the type I allele of the IL-IRa gene are worthwhile because of its correlation with stone disease. In our study, neither the IL-1beta promoter region nor the exon 5 polymorphisms were significantly different when comparing control subjects and calcium oxalate stone patients. PMID- 11762794 TI - G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells. AB - The aim of this study was to investigate the expression of G-protein coupled receptor kinases (GRKs) mRNA by RT-PCR and GRKs protein by immunohistochemistry in human detrusor cultured smooth muscle. Primary cultures of human detrusor smooth muscle cells were established using the explant method from three normal bladders. The expression of each GRK, beta-adrenergic receptor and muscarinic acethylcholine receptor (mAchR) mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical staining was also performed using primary antibodies for GRKs. The GRK2 and GRK3 transcripts were detected by RT-PCR. The m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes mRNA were also detected. Using immunohistochemistry, both GRK2 and GRK3 were found to be expressed in detrusor smooth muscle cells. These results demonstrated the existence of GRK2 and GRK3 and the co-expression of m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes in detrusor smooth muscle cells. The possibility exists that these kinases play a role in the desensitization mechanism of mAchR and beta adrenergic receptors. PMID- 11762795 TI - Simultaneous ligation of CD5 and CD28 with monoclonal antibodies restores impaired immunostimulatory function in human renal cell carcinoma. AB - Tumor cells, including renal cell carcinoma (RCC) cells, do not effectively stimulate T lymphocyte responses against specific antigens presented on their surface. Reasons for this low immunogenicity may include low or absent expression of MHC class I and/or class II molecules, as well as accessory and costimulatory molecules. We used tumor cell pretreatment with cytokines, together with monoclonal antibodies (mAbs) directed at receptors for costimulatory molecules, to render RCC cells immunostimulatory. Interferon-gamma or tumor necrosis factor alpha pretreatment enhanced expression of MHC class I and class II molecules, as well as CD54, but had only minimal effects on T cell activation. A CD28 mAb, or an even more effective combination of CD28 and CD5 mAb, induced strong primary proliferative responses of allogeneic resting T lymphocytes. Cytokine pretreatment further augmented this T cell response in vitro and allowed T cell expansion and establishment of T cell lines. Stimulation of T cells with autologous RCC cells resulted in a similar T cell activation but with the expansion of cytolytic T cells directed at autologous MHC class II molecules. These experiments demonstrate that cytokines combined with costimulatory mAbs are useful for increasing the immunogenicity of tumor cells. They also indicate. however, that autologous MHC class II expression on tumor cells, together with strong costimulation, may lead to the activation of autoreactive T cells. PMID- 11762796 TI - Estrogenic regulation of HSP90 kD synthesis in rat urinary bladder. AB - The role of heat shock protein (HSP90 kD) has been investigated in regard to its association with steroid receptors. HSP90 kD may play a role in steroid receptor stabilization and activation. Oophorectomized Sprague-Dawley rats (n = 25) were placed into five groups and injected subcutaneously with 30 microg beta-estradiol 17-benzoate in sesame oil, with one group injected with carrier oil (control). After estrogen administration, the rats were killed, and their bladders removed for immunostaining, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis demonstrated a 90-kD band in bladder homogenates, even in the absence of estrogen. However, the bands were more intense 12 and 24 h after administering estrogen. ELISA showed significant differences in HSP90 kD synthesis as early as 6 h compared to controls (P< 0.05). After 48 h the estrogen treated rats and controls were identical. The above results were confirmed by immunostaining for HSP90 kD. HSP90 kD synthesis in the rat urinary bladder is under estrogenic regulation. These findings may be relevant in the etiology and pathobiology of interstitial cystitis and menopausal voiding dysfunctions since the bladder is enriched with estrogenic receptors and is under estrogenic influence. PMID- 11762797 TI - Extravesical cryosurgical approach for VX2 bladder tumor in rabbits. AB - This study characterized the VX2 bladder cancer model in rabbits and tested the feasibility of treating bladder cancer by extravesical cryosurgery. After the growth characteristics of the VX2 bladder tumor model were determined, the VX2 tumor was inoculated into rabbits at the dome of the bladder. One week later, three freeze/thaw cycles were followed by immediate surgical repair. The control group underwent a sham operation without freezing. When the VX2 tumor is injected into the bladder wall, invasion and central necrosis occurred within I week, lymphatic metastases by 2 weeks, and lung metastases by 3 weeks after inoculation. By 4 weeks, all control rabbits had large VX2 tumors in their bladders and advanced lung metastases. Nine of the ten rabbits in the cryosurgical group had mild to moderate degrees of lung metastases, and six of them had relatively small local recurrences. One rabbit had no tumor in the bladder and only microscopic lung metastasis. The extravesical approach to cryosurgery employing bladder inversion is well tolerated. Cryosurgery exhibits modest efficacy in treating local tumors and delaying lung metastasis in this aggressive tumor model. PMID- 11762798 TI - Reduced renal vascular resistance in response to verapamil during gradated ureter obstruction in pigs. AB - Unilateral ureteral obstruction (UUO) is associated with reductions in ipsilateral renal blood flow (RBF) and glomerular filtration rate (GFR) caused by an active preglomerular vasoconstriction, where angiotensin II (ANGII) may be an important mediator. Calcium-channel blockers preferentially dilate preglomerular vessels and abolish the vasoconstrictor actions of ANGII in preglomerular arterioles of the hydronephrotic rat kidney. In this study, we, therefore, examined the effects of the calcium-channel blocker verapamil (3.65 microg/kg per minute i.v.) on RBF, GFR and renal vascular resistance (RVR) in our pig model with UUO, where ultrasonic flow probes are mounted on each renal artery and catheters placed in the abdominal aorta and both renal veins. Verapamil treatment was associated with a 34% reduction in ipsilateral RBF (from 182.6 +/- 20.5 ml/min to 120.6 +/- 12.2 ml/min, P < 0.001), which was similar to the 27% reduction in ipsilateral RBF in controls (from 194.6 +/- 13.1 ml/min to 140.6 +/- 15.2 ml/min, P < 0.001). Ipsilateral GFR was reduced by 70% in the verapamil treated pigs (from 29.0 +/- 2.6 to 8.5 +/- 0.9 ml/min, P < 0.001) and by 73% in control animals (from 29.2 +/- 3.1 to 7.6 +/- 2.1 ml/min, p < 0.001). However, the increase in RVR was significantly attenuated in the verapamil-treated pigs. Ipsilateral RVR increased by 19% in the verapamil-treated pigs (from 0.585 +/- 0.076 to 0.726 +/- 0.081 mmHg/min/ml, P < 0.05) compared with a 34% increase in control pigs (from 0.560 +/- 0.056 to 0.854 +/- 0.091 mmHg/min per milliliter, P<0.001), suggesting that an intact calcium-channel may be important for the increase in renal vascular resistance during unilateral ureter obstruction. In conclusion, the present study shows that verapamil is able to modulate the increase in renal vascular resistance in response to increased pelvic pressure. PMID- 11762799 TI - Effects of nitric oxide on the Ca2+-activated potassium channels in smooth muscle cells of the human corpus cavernosum. AB - Relaxation of the corpus cavernosum smooth muscle is an absolute prerequisite of penile erection. Potassium channels play a role in the physiologic regulation of corporal smooth muscle tone. Among the several subtypes of potassium channels, Ca2 +-activated potassium channel (KCa channel) subtypes are thought to be the most physiologically relevant in the regulation of corporal smooth muscle tone. The purpose of this study was to investigate the effects of nitric oxide (NO) and sildenafil on the KCa channels and elucidate the mechanisms of action on the KCa channels in smooth muscle cells of the human corpus cavernosum. The conventional patch-clamp technique was applied to short-term cultured smooth muscle cells of the human corpus cavernosum. Single-channel currents were recorded in cell attached or inside-out patches, and whole-cell currents were recorded in perforated-patches. In cell-attached patches, sildenafil alone did not activate the KCa channels but sildenafil enhanced the NO-induced activation of KCa channels. The open probability of KCa channels was increased significantly after application of NO donor, SIN-1 (100 microM) (47 +/- 7.1%, n = 10, P=0.002). The application of sildenafil (100 nM) with SIN-1 (100 microM) markedly increased the open probability of KCa channels (148 +/- 24%, n = 8, P < 0.001). The activation by SIN-1 or sildenafil with SIN-1 was completely blocked by pretreatment of the soluble guanylate cyclase inhibitor, ODQ (10 microM). In inside-out patches. SIN 1 or sildenafil with SIN-1 failed to activate KCa channels at pCa 7.5 (n=5). SIN 1 increased the whole cell outward K+ currents in all holding potential. The increased IK by SIN-1 was inhibited by charybdotoxin (CTX) about 70%. These data provide compelling evidence consistent with the involvement of the KCa channel subtype in modulating NO-induced relaxation responses in human corporal smooth muscle. Furthermore, the activation of KCa channels is thought to be mediated by activation of soluble guanylate cyclase, leading to increased intracellular levels of cyclic GMP and the subsequent activation of protein kinase rather than direct NO effect. PMID- 11762801 TI - Are smokers actually a bonus for the Social Security systems? PMID- 11762800 TI - Plasma levels of cyclic guanosine-3',5'-monophosphate in the cavernous and systemic blood of healthy males during different functional conditions of the penis. AB - The relaxation of cavernous arterial and trabecular smooth muscle is dependent upon the stimulation of guanylyl cyclase activity by nitric oxide (NO), which is released from nerve terminals and endothelial cells within the cavernous tissue, and the subsequent accumulation of cyclic guanosine-3',5'-monophosphate (cGMP) in the intracellular space. The present study was undertaken to determine whether or not plasma levels of cGMP in the systemic and cavernous blood of healthy male subjects change from penile flaccidity to tumescence, rigidity and detumescence. Fifteen adult healthy males were exposed to visual and tactile erotic stimuli to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein in the respective penile stages, and cGMP was determined in plasma aliquots by means of a radioimmunoassay. Mean systemic and cavernous plasma levels of cGMP in the blood samples obtained from the healthy volunteers ranged from 1.2-1.7 pmol/ ml. cGMP levels in the systemic circulation and in the cavernous blood did not change during developing erection, rigidity and detumescence. No significant differences were found between cGMP plasma levels in the systemic and cavernous blood in the different penile stages. Our results may reflect the fact that the stimulation of NO production in healthy males during sexual arousal and developing penile erection either does not yield substantial quantities of cGMP or that the rate of cGMP-extrusion from cavernous smooth muscle cells into the extracellular space accounts only for a minor fraction of plasma cGMP. Moreover, basal levels of cGMP in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection may conceal any local release of cGMP that may occur within the penile erectile tissue. Thus, we conclude that the quantification of cGMP is of no use in the evaluation of the physiologic mechanisms of penile erection in vivo. PMID- 11762802 TI - Editorial comments on 'Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study'. PMID- 11762803 TI - Radon: a likely carcinogen at all exposures. AB - BACKGROUND: Radon is a well-established lung carcinogen that has been extensively studied. Very high concentrations can occur in some underground mines. Concentrations also tend to build up in homes. MATERIALS AND METHODS: Epidemiological studies of radon-exposed miners and of residential radon and lung cancer are reviewed. Quantitative estimates of the risk of lung cancer, based on the experience of the miners, are applied to residential radon exposures in the United Kingdom. Strategies for the prevention of lung cancer induced by residential radon are discussed. RESULTS: Estimates are uncertain, but residential radon is probably responsible for about 2000 lung cancer deaths per year in the United Kingdom, or around 6% of the total, making it the second biggest cause after smoking. Over 80% of the deaths are estimated to occur at ages less than 75 and over 80% in smokers or ex-smokers. Around 90% of radoninduced deaths in the United Kingdom probably occur as a result of exposures to radon concentrations below the currently recommended action level of 200 Bq m( 3). CONCLUSIONS: Further work is needed to obtain more reliable estimates of the risk of lung cancer associated with residential radon and on the cost effectiveness of various intervention strategies before the most appropriate policies can be developed for managing exposure to this natural carcinogen. PMID- 11762804 TI - Pathogenesis of malignant ascites: Starling's law of capillary hemodynamics revisited. AB - Peritonitis carcinomatosa, indicating the presence of malignant cells in the peritoneal cavity, is a well-known complication of malignant disease. As a result, so-called malignant ascites develops. Malignant ascites is a debilitating condition for which no effective anti-tumor therapy is available. Frequent draining may be necessary to relieve pain and discomfort. Most studies regarding malignant ascites focus on diagnosis and treatment. In this paper. we will address the subject from a pathophysiologic perspective, using the characteristics of malignant ascites, Starling's equation of capillary forces, and recent knowledge regarding biologically active peptides produced by tumor cells. Following this approach. apart from decreased lymphatic ascites absorption, increased net capillary fluid-production can be identified as a contributing feature of ascites formation. The increased net filtration is due to an increase of overall capillary membrane-surface, increased capillary permeability and a subsequent increase of intraperitoneal protein concentration leading to increased intraperitoneal oncotic pressure. This sequence might be the result of biologically active peptides produced by tumor cells such as vascular endothelial growth factor and basic fibroblast growth factor. Interference with these mediators may serve as a target in future therapeutic strategies. PMID- 11762805 TI - Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study. AB - BACKGROUND: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. PATIENTS AND METHODS: Patients with chemo naive SCLC were randomized to standard-dose CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks, x4, with filgrastim 5 microg/kg/day days 4 13) to assess the impact on survival (n = 240 patients). Patients were also randomized to prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This manuscript focuses on the antibiotics question. RESULTS: The incidence of FL during the first cycle was 25% of patients in the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an overall incidence through all cycles of 43% vs. 24% respectively (P = 0.007; 1-sided). There were less Gram positive (12 vs. 4), Gram-negative (20 vs. 5) and clinically documented (38 vs. 15) infections in the antibiotics arm. The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17 patients, P = 0.013: 1-sided). However, the overall number of days of hospitalization was not reduced (P = 0.05; 1-sided). The number of infectious deaths was nil in the antibiotics vs. five (6%) in the placebo arm (P = 0.022; 2 sided). CONCLUSIONS: Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered. PMID- 11762806 TI - Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II study. AB - OBJECTIVES: New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. RESULTS: Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). CONCLUSION: Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study. PMID- 11762807 TI - A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients. AB - PURPOSE: A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week. RESULTS: One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate. CONCLUSION: The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration. PMID- 11762808 TI - Experience in treatment of metastatic pulmonary carcinoid tumors. AB - BACKGROUND: The only cure for patients with pulmonary carcinoids is surgery. In the present paper, we report the results of medical treatment of patients with metastatic tumors, their circulating hormone markers, and immunohistochemical profile of the tumors. PATIENTS AND METHODS/RESULTS: The response to systemic antitumoral treatment was studied in 31 patients with metastatic pulmonary carcinoids. Median survival from treatment start was 25 months. Alpha-interferon treatment has resulted in stable disease in 4 of 27 patients (median duration 15 months), while 23 patients showed progressive disease. Somatostatin analogues given as single drug treatment resulted in progressive disease. Streptozotocin and 5-fluorouracil resulted in progressive disease in seven of seven patients. Stable disease was obtained for 8 and 10 months respectively in two of two patients treated with streptozotocin + doxorubicin. Two of eight patients treated with cisplatinum + etoposide showed a significant decrease in tumor size lasting six and eight months respectively, and one displayed stable disease for seven months. Elevation of plasma chromogranin A was seen in 93%. CONCLUSIONS: The results of systemic antitumoral treatment of pulmonary carcinoids with distant metastases are generally discouraging. Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with streptozotocin or paclitaxel may be of value. Alpha interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker. PMID- 11762809 TI - Weekly docetaxel (Taxotere) in patients with metastatic breast cancer. AB - BACKGROUND: Docetaxel (Taxotere) has demonstrated high antitumour activity in first- and second-line treatment of metastatic breast cancer. This study analysed the efficacy and toxicity of docetaxel given weekly. PATIENTS AND METHODS: Thirty five patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks without treatment. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression. All patients had received prior chemotherapy: 32 and 5 patients had received prior anthracycline-containing and taxane-containing regimens, respectively. Docetaxel was administered for a total of 359 doses (median 9. range 6-22). RESULTS: There was one complete response (3%), 11 partial responses (31%), 17 patients with stable disease (49%) and six with disease progression (17%). Overall response rate was 34% (95% confidential interval (95% CI): 18%-51). Median survival was 307 days; median progression-free survival was 2.6 months (range 1.5 to > or = 5.5 months). Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1-2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haematotoxicity. and stopped in one patient due to painful nail toxicity. CONCLUSION: Weekly administration of docetaxel at a dose of 35 mg/m2 is effective and of low toxicity in patients with metastatic breast cancer. PMID- 11762810 TI - A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma. AB - BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX in chemotherapy-naive patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL). time to progression and overall survival. PATIENTS AND METHODS: Twenty-two patients (median age 65) were enrolled. CAELYX was administered to the first five patients at a dose of 30 mg/m2 three-weekly. Two of these patients were dose escalated to 50 mg/m2 four weekly. Subsequent patients were all treated on the latter schedule. RESULTS: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. CONCLUSION: No objective responses were seen with CAELYX in this study. CAELYX was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials. PMID- 11762811 TI - A phase II study of gemcitabine in gallbladder carcinoma. AB - BACKGROUND: Due to the high mortality rates from gallbladder carcinoma in Chile, we conducted a phase II trial to test the efficacy and safety of gemcitabine in patients with locally advanced or metastatic gallbladder carcinoma. PATIENTS AND METHODS: From January 1998 to February 2000, 26 patients with metastatic or unresectable gallbladder carcinoma and no prior chemotherapy received gemcitabine 1,000 mg/m2 over 30 minutes weekly for three weeks followed by a week of rest. RESULTS: Patients received a median of 4.2 cycles (range 1-10). Out of the 25 patients whose response could be evaluated, 9 went into partial remission, an overall response rate of 36% (95% confidence interval (95% CI): 17.1% to 57.9%). In six (25.0%) patients, the cancer remained stable, and in 10 (40%) it progressed. Median survival time was 30 weeks (range 7-80+. Hematological toxicities were mild, with no cases of febrile neutropenia or hemorrhage. However, four and one patient(s) had grades 1-2 and 3-4 neutropenia, respectively, and two patients had grade 2 thrombocytopenia. Nine patients experienced grade 1-2 nausea/vomiting, but were able to continue treatment. There were no toxic deaths. CONCLUSIONS: In this phase II trial, gemcitabine is an active chemotherapy in metastatic or inoperable gallbladder carcinoma, with a manageable toxicity profile. PMID- 11762812 TI - A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation. RESULTS: ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea. CONCLUSIONS: The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate. PMID- 11762813 TI - Multicenter phase II-III study of oxaliplatin plus cyclophosphamide vs. cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients. AB - PURPOSE: A phase II-III randomised study to compare safety and efficacy of an oxaliplatin/cyclophosphamide (OXAC) combination, vs. the reference combination of cisplatin/cyclophosphamide (CPC), in untreated advanced ovarian cancer patients. PATIENTS AND METHODS: 182 patients were enrolled, of whom 177 were treated: 86 with OXAC (130 mg/m2 oxaliplatin two-hour intravenous (i.v.) infusion, 1,000 mg/m2 cyclophosphamide two-hour i.v. infusion), and 91 with CPC (100 mg/m2 cisplatin one-hour i.v. infusion. 1,000 mg/m2 cyclophosphamide two-hour i.v. infusion). Treatment cycles were repeated every three weeks (maximum of six cycles). RESULTS: The main toxicities, which were significantly less severe in the OXAC arm, were myelosuppression and vomiting, including (OXAC vs CPC, % patients): grade 3-4 leukopenia (37% vs. 56%), and anaemia (7% vs. 32%), with blood transfusions in 8% vs. 21%. In the OXAC arm, 64% of surgically assessable patients and 33% of clinically assessable patients achieved an objective response. In the CPC arm, 67% patients achieved a surgical response and 42% achieved an objective clinical response. In the OXAC and CPC arms, median progression free-survival was 13.0 and 13.3 months, and overall survival was 36.0 and 25.1 months respectively, without statistically significant difference. CONCLUSION: The activity and time-related parameters of the OXAC and CPC combinations in advanced ovarian cancer patients, are comparable. Combined with the better safety profile of the oxaliplatin-containing regimen, this confirms the interest of oxaliplatin combined with active new agents in this indication. PMID- 11762814 TI - Combination chemotherapy with gemcitabine and ifosfamide as second-line treatment in metastatic urothelial cancer. A phase II trial conducted by the Hellenic Cooperative Oncology Group. AB - PURPOSE: The aim of the study was to evaluate the efficacy and safety of the combination of gemcitabine and ifosfamide as a second-line treatment for advanced urothelial cancer. PATIENTS AND METHODS: Thirty-four patients with metastatic urothelial cancer previously treated with cisplatin (CDDP)/ carboplatin (CBDCA) and/or taxanes-based chemotherapy were studied. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 and ifosfamide at a dose of 2 g/m2 on days 1 and 8 with adequate amount of Mesna. every three weeks. Hematopoietic growth factors were given between days 3 to 5 and 12 to 16 to maintain the treatment schedule. RESULTS: On an intent to treat basis, there was one complete response (CR) (3%) (95% confidence interval (95% CI): 0% to 10%) and six partial responses (PR) (18%) (95% CI: 7% to 34%). inducing an objective response rate (RR) of 21% (95% CI: 9% to 38%); 12 (35%) patients achieved a stable disease (SD) and 15 (44%) a progressive disease (PD). The median time to tumor progression (TTP) was four months (range, 0.52 to 21.6 months) and the median survival nine months (range 0.52 to 28 months). This regimen also provided the opportunity for symptomatic improvement of pain, dysuria, haematuria and leg oedema. Grade 3-4 neutropenia was experienced by 9 (27%) patients, grade 3 4 anemia by 6 (18%) and grade 3-4 thrombocytopenia by 4 (12%). Six patients were hospitalized due to febrile neutropenia. Despite the prophylactic use of hematopoietic growth factors, 8 (23.5%) patients required dose reduction due to myelosuppression. Grade 3 alopecia occurred in 14 (41%) patients, grade 3-4 nausea in 1 (3%), grade 2 fever in 3 (9%), grade 2-3 diarrhea in 2 ( 6%) and grade 2 allergic reaction in 1 (3%). CONCLUSION: We conclude that the combination of gemcitabine and ifosfamide is an active salvage regimen for the treatment of urothelial cancer and that the treatment also has a tolerable toxicity profile; it warrants further investigation in combination with CDDP in chemotherapy-naive patients. PMID- 11762815 TI - Alterations of routine blood tests in adult patients with soft tissue sarcomas: relationships to cytokine serum levels and prognostic significance. AB - BACKGROUND: It has been reported that malignancy is often accompanied by hematological alterations and that such alterations may correlate with poor prognosis. It has also been demonstrated that several cytokines may be synthesized by many malignant tumors and that elevated serum levels of some cytokines are associated with changes in blood cell counts in cancer patients. However, so far little is known about the prognostic significance and mechanism of hematological changes in soft tissue sarcomas. The aim of the study was to evaluate the routine blood tests of disturbances in patients with malignant soft tissue tumors prior to treatment and to correlate these results with selected cytokine serum levels, clinicopathological features of the tumors and patient survival. PATIENTS AND METHODS: 145 patients (75 males, 70 females; mean age 49.97 +/- 16.9 yrs) with histologically confirmed soft tissue sarcomas before treatment were enrolled into the study. In all these patients we evaluated routine blood tests (hemoglobin level HGB, white blood cell count WBC, platelet count PLT, white blood cell differential count-neutrocyte count NE, lymphocyte count LY, monocyte count MN, eosinophile count EO) and serum levels of 13 cytokines and soluble cytokine receptors (IL-6, IL-8, IL-10, TNFalpha, G-CSF, M CSF, bFGF, VEGF, IL-1ra, sIL-2R. sIL-6R. TNF RI, TNF RII)--ELISA method. Peripheral blood samples from 50 healthy volunteers served as control. Statistical analysis was performed using Kolmogorov-Smirnov and Mann-Whitney U tests, chi2 test (P < 0.05), where appropriate. For survival analysis the Kaplan Meier method, log-rank test and multivariate Cox analysis were applied. RESULTS: Alterations of at least one of the standard blood tests were found in 43.4% of all cases. The most frequent alterations were: neutrophilia (28.3% of cases), leukocytosis (27.6%), decreased HGB (25.5%), monocytosis (19.3%) and thrombocytosis (14.5%); they correlated strongly with elevated serum levels of several cytokines and soluble cytokine receptors (particularly: sIL-2R, IL-6, IL 8, M-CSF, VEGF, TNF RI, TNF RII) (P < 0.001). Lymphocytopenia (LY < 1.0) found in 10.3% of patients correlated strongly with increased serum levels of IL-6, sIL 2R, TNF RI. In parallel, we found a significant difference in serum levels of 11 of 13 cytokines (IL-1ra. sIL-2R, IL-6, IL-8, IL-10, TNF RI, TNF RII, TNFalpha, M CSF, bFGF, VEGF) (P < 0.001) in soft tissue sarcoma patients compared to healthy controls. Hematological alterations were significantly more frequent in patients with advanced tumors. In multivariate analysis we found no prognostic significance of any of the routine blood tests in soft tissue sarcoma patients. CONCLUSION: The results of this study demonstrate that hematological alterations, which occur in over 40% of soft tissue sarcoma cases, are found more frequently in patients with advanced tumors. Strong correlations between the occurrence of hematological abnormalities and elevated serum levels of several cytokines and soluble cytokine receptors, suggest that the former may develop as a result of cytokine misbalance frequently detected in soft tissue sarcoma patients. However, the results of routine blood tests alone are no independent prognostic factor for survival of soft-tissue sarcoma patients. PMID- 11762816 TI - Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease. AB - BACKGROUND: There is considerable debate as to the optimum schedule of bisphosphonate treatment in advanced malignancy. Short term studies using symptomatic response and biochemical markers of bone resorption may provide useful insight into differences between agents. PATIENTS AND METHODS: Fifty-one patients with metastatic bone disease were randomly allocated to either oral clodronate 1,600 mg daily (group 1), intravenous clodronate followed by the same schedule of oral clodronate (group 2). or intravenous pamidronate 90 mg monthly (group 3). No radiotherapy was delivered or other systemic anticancer treatments were allowed except for long term endocrine therapy. Bone resorption was assessed by measurement of urinary collagen crosslinks. At each visit a pain score was recorded. RESULTS: Symptomatic response was more frequent in the pamidronate group than in patients receiving clodronate. Nine of sixteen patients experienced a sustained improvement in pain score in the pamidronate-treated group, in contrast to only 4 of 16 and 2 of 11 patients in groups 1 and 2, respectively. There was a significant improvement in pain scores in the pamidronate arm compared with the clodronate treated patients after both three months of treatment (P <0.01) and at the last measurement (P <0.05). Biochemical changes correlated with changes in the pain score (P = 0.01). CONCLUSION: Intravenous pamidronate appears to be more effective than oral clodronate in both controlling symptoms and suppressing bone resorption. PMID- 11762818 TI - Diffuse large B-cell lymphoma with primary retroperitoneal presentation: clinico pathologic study of nine cases. AB - Diffuse large B-cell lymphoma primarily presenting in the retroperitoneum (PRLBCL) has been the object of occasional reports, all based on dated techniques. MATERIALS AND METHODS: Nine PRLBCLs--with clinical information and paraffin blocks available--were reviewed on morphologic, immunohistochemical and molecular grounds. RESULTS: At microscopic examination, the cases were characterized by a diffuse proliferation of large cells (CD20+, CD79a+, CD3-), displaying a wide rim of cytoplasm (clear in seven instances and acidophilic in two), associated with sclerosis and frequent compartmentalization. Phenotypic and molecular analyses showed that: a) three cases were bcl-2+, bcl-6+, HLA-DR+, and CD10+ (1/3), with associated follicular dendritic cell (FDC) component and bcl-2 gene rearrangements; b) four cases were bcl-2, bcl-6, HLA-DR, CD10, FDC, and bcl 2 gene rearrangement negative; c) two cases had border-line characteristics (bcl 2+, bcl-6+, FDC+, HLA-DR-, CD10-, and bcl-2 gene rearrangement-). The first subgroup was thought to be of follicular derivation, as was the third due to bcl 6 and FDC stains. Of the corresponding five patients, three are in complete remission and two died of disease within 12 months. No obvious, normal counterpart was detected in the remaining four tumors: the corresponding patients died of disease in 3-23 months. The problem of similarities between PRLBCL and primary mediastinal LBCL is discussed. CONCLUSIONS: Although the present series is small, our findings suggest that PRLBCL may represent a more heterogeneous group of tumors than previously thought, which merits further phenotypic and molecular studies to broaden the understanding of its histogenesis and behavior. PMID- 11762817 TI - Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma. AB - BACKGROUND: Dexamethasone. cytarabine (ara-C), and cisplatin (DHAP) can be used effectively to treat patients with non-Hodgkin's lymphoma (NHL). We hypothesized that substitution of cisplatin by oxaliplatin (L-OHP) could result in less toxicity and greater efficacy. L-OHP is active in patients with lymphoma. It produces mild myelosuppression and is devoid of renal toxicity. We report on a phase II study of dexamethasone, high-dose ara-C, and L-OHP (DHAOx) used to treat patients with NHL who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifteen patients were given DHAOx. They had failed to achieve a CR with initial chemotherapy or had recurrent disease. DHAOx consisted of dexamethasone, 40 mg/day (days 1 to 4): L-OHP, 130 mg/m2 (day 1); and ara-C, 2,000 mg/m2 every 12 h (day 2). Treatment was repeated every 21 days. RESULTS: Patients received a median of four courses of DHAOx. Myelosuppression and transient sensory peripheral neuropathy were the most prominent toxic effects. Serum creatinine levels did not increase in patients with normal renal function, nor in patients who had renal impairment before DHAOx. The median follow-up time from the start of DHAOx treatment was 17 months. Eight patients (53%) achieved a CR, and three patients (20%) had a PR. Responses were achieved by patients with lymphomas of various histologies that included mainly the follicular subtype, and by patients with and without resistance to prior chemotherapy. None of the eight responders have relapsed from CR at 4+. 6+, 14+, 15+, 19+, 20+, 24+, and 24+ months. They had various types of therapy after DHAOx. Disappearance of molecular markers was observed in all four patients who achieved a CR and whose tumor cells carried molecular abnormalities. CONCLUSION: DHAOx possesses characteristics of toxicity which compare favorably to those reported with DHAP, and it is useful as a salvage treatment for patients with NHL. Larger studies are required to establish the therapeutic potential of the regimen. PMID- 11762819 TI - Fludarabine and mitoxantrone: effective and well-tolerated salvage therapy in relapsed indolent lymphoproliferative disorders. AB - BACKGROUND: Prior studies of the combination of fludarabine, mitoxantrone and dexamethasone have yielded high response rates but are associated with a significant risk of opportunistic infections, predominantly Pneumocystis Carinii pneumonia (PCP) requiring routine prophylaxis. PATIENTS AND METHODS: We evaluated the combination of fludarabine (25 mg/m2/day x 3) and mitoxantrone (10 mg/m2 x 1) without corticosteroids or PCP prophylaxis in 29 patients with relapsed or refractory indolent lymphoproliferative disorders; median age 56 years, 62% refractory to preceding chemotherapy. RESULTS: A median of four cycles was administered without cumulative myelosuppression. Neutropenia <0.5 x 10(9/)l was seen in 16% of cycles. Infections complicated 10.4% of cycles. with impaired performance status (> or = ECOG 2) and increased age ( > 56 years) significant risk factors (P < or = 0.01). No cases of PCP were encountered. The response rate was 90%, median remission duration 11.9 months and the median survival 57 months. Peripheral blood progenitor cell mobilization was attempted in 11 patients and yielded > or = 2 x 10(6) CD34+ cells/kg in only 5 cases (45%). CONCLUSIONS: High response rates can be attained with fludarabine and mitoxantrone in combination without corticosteroids, and routine PCP prophylaxis can safely be omitted. Peripheral blood progenitor collections are problematic in these heavily pretreated patients. PMID- 11762820 TI - Quality of life in patients at risk of medullary thyroid carcinoma and followed by a comprehensive medical network: trends for future evaluations. AB - BACKGROUND: As shown in a previous study, the knowledge of the genetic risk in individuals belonging to families at risk of medullary-thyroid carcinoma (MTC) could be associated with impaired quality of life (QoL). PATIENTS AND METHODS: In the present study, we compared the QoL scores obtained in the same period with the subjective quality of life profile (SQLP): in 82 individuals at risk of MTC who had been tested for Ret-mutations; in 200 women at risk of familial breast/ovarian cancer syndrome (BOC); and in a control population of 3,501 healthy volunteers. RESULTS: Significant differences were observed in favour of healthy volunteers as well as individuals at risk of MTC, over women at risk of BOC (mean scores: 0.89, 0.85, and 0.64, respectively, P < or = 0.001), but QoL scores were not statistically different between individuals at risk of MTC and the control population (P = 0.2). However, they were significantly inferior in the subgroup of germline Ret-mutation carriers, as compared to the control population (mean scores: 0.73 and 0.89, P = 0.04). In the latter, the relationships with the children and the family were the most important facets of their QoL. CONCLUSION: Our results confirm the potentially negative impact of the knowledge of the genetic risk of cancer and its consequences in terms of morbidity and follow-up, on the QoL in people followed at oncogenetic visits. PMID- 11762821 TI - Changed trends of cancer mortality in the elderly. AB - BACKGROUND: Trends in cancer mortality for the elderly have long been unfavourable. MATERIALS AND METHODS: Mortality from 12 major cancer sites, plus total cancer mortality at age 65-84 in 23 European countries, the US and Japan was analyzed. RESULTS: Between the late 1980s and the late 1990s total cancer mortality at age 65 to 84 has been declining in the European Union (UE) (-5.5% in males, -4.5% in females), in United States (US) males (-2.3%), but not females (+4.4%), and in Japanese females (-5.6%), but not males (+6.3%). Cancer mortality in the elderly rose for both sexes in eastern Europe. Gastric cancer mortality declined in all the areas. Lung cancer rates declined over the last decade by 8.5% in males in the EU. and by 0.9% in the US. Rates were still increasing in eastern Europe, in Japanese males and in females in all areas. Pancreatic mortality rates were increasing in both sexes in the EU and Japan up to the late 1980s, and in eastern Europe up to the 1990s, whereas rates for US males have been declining over recent years. Breast cancer mortality has declined over the last decade by 8% in the US and by 3% in the EU, while it has risen in eastern Europe and in Japan. Mortality from breast and prostate as well as ovarian cancer remained however low in elderly Japanese. Prostate cancer mortality declined in the EU and in the US, whereas it rose in eastern Europe and in Japan. Mortality from lymphomas and multiple myeloma rose in both sexes and various geographic areas, but improved diagnosis and certification may have played a role in these trends. Mortality from leukemia in the elderly increased in eastern Europe and Japan. but was stable in the US and the EU. CONCLUSIONS: Cancer mortality in the elderly has stopped systematically rising, and is on the decline in males since the late 1980s. PMID- 11762822 TI - Identification of the B-cell tumor-specific molecular fingerprint using non radiolabelled PCR consensus primers. AB - BACKGROUND: The complementarity determining region 3 (CDR3) of the immunoglobulin (Ig) heavy chain variable region (VH) is the most reliable molecular fingerprint for most if not all human B cells. The nucleotide sequence encoding for any B cell tumor-specific VH CDR3 is currently identified by PCR sequencing based on procedures involving the usage of either radioactive materials, patient/family specific primers, or bacterial cloning. PATIENTS AND METHODS: In six consecutive patients with follicular lymphoma we assessed the feasibility of a method that allows for identification of the tumor-specific VH CDR3 using consensus primers while avoiding both radioactive materials and bacterial cloning procedures. RESULTS: The tumor-specific VH CDR3 was successfully identified in all six patients in nearly half the time typically required by any other method currently utilized. The feasibility of the proposed method was not significantly affected either by the tumor-specific Ig isotype, or by the tumor infiltration in the original biopsy specimen. In the three patients for whom tumor specimen-derived hybridomas were available, the tumor-specific VH CDR3 was also found in at least 8 of 10 of them. CONCLUSIONS: The proposed method allows the ability to quickly identify the B-cell tumor-specific VH CDR3 using consensus primers while avoiding radioactive materials and bacterial cloning procedures. PMID- 11762823 TI - PET and PLAP in suspected testicular cancer relapse: beware sarcoidosis. AB - A 31-year-old man previously treated with chemotherapy for metastatic testicular cancer presented with new mediastinal lymphadenopathy and peripheral lung opacities. Serum tumour markers were not elevated and a PET (positron emission tomography) scan revealed increased FDG (fluoro-deoxyglucose) uptake in the lungs and mediastinum consistent with testis cancer relapse. A biopsy of a mediastinal lymph node was performed and the pathology was that of sarcoidosis. Immunohistochemistry however was positive for PLAP (placental alkaline phosphatase) and negative for EMA (epithelial membrane antigen). This immunohistochemical profile raised concerns that the observed pathology represented a sarcoid reaction to micro-metastatic testicular cancer relapse. We performed immunohistochemical pathology analysis on four known cases of sarcoidosis and found the same immunohistochemical-staining pattern. This case highlights the problem of specificity when interpreting the significance of PET scans and immunohistochemical analysis in this situation. Sarcoidosis, a condition that has been associated with testicular cancer, should always be considered in the differential diagnosis. PMID- 11762824 TI - Metastatic malignant ameloblastoma responding to chemotherapy with paclitaxel and carboplatin. AB - We report an unusual case of metastatic ameloblastoma, involving lung and pleura. that repeatedly responded to systemic treatment with paclitaxel and carboplatin. suggesting principle chemosensitivity of this rare disease. PMID- 11762825 TI - Prolonged neutropenia following anti CD20 therapy in a patient with relapsed follicular non-Hodgkin's lymphoma and corrected with IVIG. PMID- 11762826 TI - Use of gemcitabine (GEM) in advanced myelodysplastic syndromes. PMID- 11762827 TI - Endothelial cell formation of focal adhesions on hydrophilic plasma polymers. AB - Endothelial cell (EC) formation and distribution of both actin stress fibers and focal contacts on hydrophilic plasma polymers derived from gamma-butyrolactone (GBL) and n-vinylpyrrolidone (NVP) were examined to determine their ability to support endothelial cell growth in comparison to fibronectin. One hour after seeding, cells adhered and spread moderately on fibronectin with the development of defined actin stress fibers and focal adhesions compared to NVP and GBL, on which the cells were spread with poorly developed stress fibers and a perinuclear localization of vinculin. At 3 h, cells continue to spread more on fibronectin and NVP than GBL, and the cells on fibronectin had well-defined stress fibers terminating with sharp spikes of vinculin, typical of focal adhesions. At this time point, paxillin, a signaling component of focal adhesion complex, was predominantly localized at the focal contacts for well-spread EC on fibronectin and NVP, whereas it was almost entirely concentrated in the perinuclear region of less-spread cells on GBL. However, by 24h, cells were much more spread on all three surfaces with defined stress fibers and focal contacts although EC expression of vinculin and paxillin was moderate on GBL compared to fibronectin and NVP. These results suggest that EC can form cytoskeletal structures necessary for cell survival on plasma polymers, especially on more hydrophilic NVP, which could be exploited as interface material for seeding endothelial cells. PMID- 11762828 TI - Osteoblast behaviour on HA/PE composite surfaces with different HA volumes. AB - A hydroxyapatite (HA) reinforced polyethylene (PE) composite (designated HAPEX), with high mechanical specification and a bioactive HA phase, has been optimised as a bone analogue material. Manufacturing conditions and machining of the materials were carefully controlled to give a reproducible material surface roughness with minimal batch variation. The effect of surface composition was examined in vitro using primary human osteoblasts (HOB). HOBs were cultured in direct contact with the test materials containing 20% and 40% vol. HA. The results showed that 40% HA/PE enhanced cellular activity by increasing proliferation rate and differentiation compared to the 20% vol. HA composite. The cytoskeletal organisation of the cells was also examined and HOBs cultured on 40% HA/PE were flatter and had an enhanced rate of cytoskeletal organisation and an increase in focal contact points compared to the 20% HA/PE. PMID- 11762829 TI - Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects. AB - Several studies have reported enhanced repair of damaged cartilage following implantation of mesenchymal stem cells (MSCs) into full-thickness cartilage defects suggesting that the cells in the repair tissue were derived from the implant. However, it cannot be excluded that the enhanced tissue repair is derived from host cells recruited to the defect in response to the implant, rather than the re-population of the tissue by the implanted MSCs. Our objective was to study the short-term fate of fluorescently labeled MSCs after implantation into full-thickness cartilage defects in vivo. The fluorescent dye used in our studies did not affect MSC viability or their ability to undergo osteogenic and chondrogenic differentiation in vitro. MSC gelatin constructs were implanted into full-thickness cartilage defects in goats. These cells retained the dye and were detectable by histology and flow cytometry. At intervals spanning 2 weeks post implantation we observed gradual loss of implanted cells in the defect as well as fragments of gelatin sponge containing labeled MSCs in deep marrow spaces indicating fragmentation, dislodgement and passive migration. Fluorescent labeling enabled us to determine whether the implanted cells were lost during early time points after implantation as well as their spatial orientation throughout the defect. By determining the fate of implanted cells, new biomaterials could be engineered to correct undesirable characteristics. Testing of new biomaterials in short-term in vivo models would provide faster optimization for cell retention needed for successful, long-term cartilage regeneration. PMID- 11762830 TI - Iodine-containing cellulose mixed esters as radiopaque polymers for direct embolization of cerebral aneurysms and arteriovenous malformations. AB - The present study deals with the synthesis and characterization of radiopaque polymers which could, when solubilized in an appropriate water-miscible solvent, be useful embolic materials for the treatment of cerebral aneurysms and arteriovenous malformations. For this purpose cellulose (both microcrystalline and powdered) and partially substituted cellulose acetate (two different viscosity grades) were selected as starting materials to prepare iodine containing polymers through various synthetic routes. The materials obtained were characterized by IR and NMR spectroscopy, molecular weight, iodine content, radiopacity and solubility in selected injectable organic solvents. The embolic liquids were evaluated for their precipitation behavior in a phosphate buffer solution (pH 7.4) mimicking physiological conditions using an in vitro aneurysm model. A sheep model was also used to assess in vivo the radiopacity and precipitation properties of a highly concentrated solution of a cellulose acetate 2,3,4-triiodobenzoate mixed ester. All materials with 4-iodo- and 2,3,5 triiodobenzoyl groups gave sufficient radiopacity to be regarded as possible embolization materials, whereas iododeoxycellulose and iododeoxycellulose acetate were not radiopaque because of their low iodine content. Esters synthesized using cellulose as starting material were not soluble in the selected organic solvents due to the presence of many residual hydroxyl groups, but could be used for other biomedical applications where insoluble radiopaque materials are used. In contrast, solubility of the materials as well as satisfactory precipitation properties were ensured using cellulose acetate as the starting material. In conclusion, cellulose acetate iodobenzoate mixed esters dissolved in diglyme or dimethyl isosorbide (dimethyl sulfoxide is probably less appropriate because of its toxicity and hemolytic properties) could be useful embolic liquids for the treatment of cerebral aneurysms or arteriovenous malformations. PMID- 11762831 TI - Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite. AB - Hydroxyapatite (HA)-reinforced polymers have been proposed as a method of improving the biological properties of bone cements and implant materials. For example, bone cements based on polymethylmethacrylate (PMMA) have long been used to secure orthopedic implants to the skeleton. This composite could also be used as a polished coating on other materials or in bulk form, shaped or molded, to custom fit a specific clinical need. However, complications may occur as a result of the limited mechanical and biological properties of PMMA. The purpose of this investigation was to determine whether the incorporation of HA in a PMMA matrix would enhance the biological properties of osteoblast response as compared to PMMA alone. Fetal rat calvarial osteoblasts were plated on discs of PMMA, PMMA/HA, commercially pure titanium (CpTi) and tissue culture polystyrene (control). Osteoblast attachment and day 2 proliferation were similar on all implant materials, whereas, day 8 proliferation on PMMA/HA was significantly higher than on PMMA and similar to CpTi and control. Extracellular matrix production was examined by immunohistochemistry which indicated that osteoblasts cultured on PMMA/HA showed a more distinct networked pattern of organized fibronectin. Histochemical staining of mineralization was examined by confocal microscopy which demonstrated a higher degree of mineralization in nodules formed on PMMA/HA as compared to PMMA. Together, these results indicate that the addition of HA in a PMMA matrix improves osteoblast response as compared to PMMA alone. Therefore, the incorporation of HA into a PMMA matrix may be a useful method to provide PMMA materials with enhanced osteogenic properties. PMID- 11762832 TI - Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G CSF, a model protein. AB - A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP 55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins. PMID- 11762833 TI - Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. AB - Quaternized modifications of chitosan present characteristics that might be useful in DNA condensing and efficient gene delivery. Trimethylated chitosan (TMO) was synthesized from oligomeric chitosan (<20 monomer units). TMOs spontaneously formed complexes (chitoplexes) with RSV-alpha3 luciferase plasmid DNA. These complexes were characterized by photon correlation spectroscopy and were investigated for their ability to transfect COS-1 and Caco-2 cell lines in the presence and absence of fetal calf serum and compared with DOTAP (N-[1-(2,3 dioleoyloxy)propyl]-N,N,N-trimethylammonium sulphate) lipoplexes. Additionally, their effect on the viability of the respective cell cultures was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results showed that quaternized chitosan oligomers were able to condense DNA and form complexes with a size ranging from 200 to 500 nm. Chitoplexes proved to transfect COS-1 cells, however, to a lesser extent than DOTAP-DNA lipoplexes. The quaternized oligomer derivatives appeared to be superior to oligomeric chitosan. The presence of fetal calf serum (FCS) did not affect the transfection efficiency of the chitoplexes, whereas the transfection efficiency of DOTAP DNA complexes was decreased. Cells remained 100% viable in the presence of chitosan oligomers whereas viability of DOTAP treated cells decreased to approximately 50% in both cell lines. Both DOTAP-DNA lipoplexes and chitoplexes resulted in less transfection efficiency in Caco-2 cell cultures than in COS-1 cells; however quaternized chitosan oligomers proved to be superior to DOTAP. Effects on the viability of Caco-2 cells were similar to the effects observed in COS-1 cells. We conclude that trimethylated chitosan-DNA complexes present suitable characteristics and the potential to be used as gene delivery vectors. PMID- 11762834 TI - Generation of mesoscopic patterns of viable Escherichia coli by ambient laser transfer. AB - We have generated mesoscopic patterns of viable Escherichia coli on Si(1 1 1), glass, and nutrient agar plates by using a novel laser-based transfer process termed matrix assisted pulsed laser evaporation direct write (MAPLE DW). We observe no alterations to the E. coli induced by the laser-material interaction or the shear forces during the transfer. Transferred E. coli patterns were observed by optical and electron microscopes, and cell viability was shown through green fluorescent protein (GFP) expression and cell culturing experiments. The transfer mechanism for our approach appears remarkably gentle and suggests that active biomaterials such as proteins, DNA and antibodies could be serially deposited adjacent to viable cells. Furthermore, this technique is a direct write technology and therefore does not involve the use of masks, etching, or other lithographic tools. PMID- 11762835 TI - Apatite-forming ability of CaO-containing titania. AB - It was recently shown that titanium metal and its alloys spontaneously form a bonelike apatite layer on their surfaces in the living body and bond to the bone through the apatite layer, when the sodium ions are incorporated into titanium oxide layer of their surfaces by chemical and heat treatments. It is expected that their apatite-forming ability, and hence their bone-bonding ability, could be enhanced, if the calcium ions are incorporated into their surface titanium oxide layers instead of the sodium ions, because the calcium ions released from their surface layers can increase the ionic activity product of the apatite of the surrounding fluid more effectively than the sodium ions. In the present study, in order to investigate the effect of incorporation of the calcium ions into the titanium oxide layer on its apatite-forming ability, apatite-forming abilities of titania gels which have different CaO contents and subjected to different heat treatments were examined in a simulated body fluid with ion concentrations nearly equal to those of the human blood plasma. It was found that CaO-containing gels do not form the apatite on their surfaces as far as they take an amorphous phase in spite of the fact that they release larger amounts of the calcium ions with increasing CaO contents of the gels. They form the apatite when they take an anatase-like structure even though they do not contain CaO. These results indicate that a specific structure of the titanium oxide is more important for the apatite nucleation than the magnitude of the ionic activity products of the apatite in the surrounding fluid. PMID- 11762836 TI - Carbonate apatite coating on titanium induced rapidly by precalcification. AB - Chemical treatments have been thought to be promised methods for improving bioactivity of titanium. In this work, the effect of precalcification with boiling saturated Ca(OH)2 solution on bioactivation of titanium was investigated. After precalcification and soaking in supersaturated Ca-P solution (SCP), calcium phosphate rapidly precipitated onto the surfaces of titanium, and after only three days an uniform apatite layer was found up to thickness of a few micrometers. The observation using scanning electron microscopy (SEM) showed that the coating was composed of a number of small crystal grains. The investigation by X-ray energy dispersion spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that the coating was Ca deficient carbonate apatite. Based on the analyses for the surfaces and SCP, a mechanism of precipitation of apatite was proposed in thermal dynamics and kinetics. PMID- 11762837 TI - In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. AB - A novel injectable-chitosan-based delivery system with low cytotoxicity was fabricated in the study. The chitosan microspheres with small particle size, low crystallinity and good sphericity were prepared by a spray-drying method followed by treating with a crosslinker. In the study, a naturally occurring crosslinking reagent (genipin), which has been used in herbal medicine and in the production of food dyes, was used to crosslink the chitosan microspheres. The glutaraldehyde crosslinked counterparts were used as a control. Histological study of the genipin-crosslinked chitosan microspheres injected intramuscularly into the skeletal muscle of a rat model showed a less inflammatory reaction than its glutaraldehyde-crosslinked counterparts. The results of the scanning electron microscopic examination indicated that the glutaraldehyde-crosslinked chitosan microspheres retrieved at 12-week postoperatively were already degraded into a loose and porous structure. However, the degradation of the genipin-crosslinked chitosan microspheres was not significant after 20 weeks of implantation. The results of the study demonstrated that the genipin-crosslinked chitosan microspheres have a superior biocompatibility and a slower degradation rate than the glutaraldehyde-crosslinked chitosan microspheres. Accordingly, the genipin crosslinked chitosan microspheres may be a suitable polymeric carrier for long acting injectable drug delivery. PMID- 11762838 TI - Investigation of primary cell-biomaterial interactions using silver nitrate staining of nucleolar organising regions. AB - The quantification of silver nitrate staining of nucleolar organising regions (AgNORs) within the nucleus of the cell has been shown to give a relative measure of the metabolic activity of the cell. In the present study, silver nitrate staining was utilised to identify metabolic variations in cells cultured on different surfaces and compared with proliferative activity assessed using bromodeoxyuridine (BrdU) uptake. Primary osteoblast and periosteal cells, isolated from the calvaria of neonate rats, were cultured on tissue culture-grade (TCPS) and bacteriological-grade (BACPS) polystyrene petri dishes for 3, 5, 7 and 9 days (silver nitrate) or 14 days (BrdU). The phenotype of the cells was examined using RT-PCR of the mRNA for osteocalcin, collagen 1a, alkaline phosphatase and osteopontin. The number and area of AgNORs and the proportion of BrdU positive cells were statistically different in cells cultured on TCPS compared with BACPS at each culture period tested. The results suggest that the metabolic activity and proliferation of cells were affected by the substrate which they colonise. PMID- 11762839 TI - Material properties of polymerized NDGA-collagen composite fibers: development of biologically based tendon constructs. AB - Methods for stabilizing collagen-based materials with catechol containing monomers were developed in order to produce fibers with mechanical properties in tension comparable to those of normal tendon. Fibers produced from pepsin solubilized, bovine tendon type I collagen were polymerized with the di-catechol nordihydroguaiaretic acid (NDGA). Polymerization was based on the chemical oxidation of the constituent o-catechols to reactive o-quinone functionalities. NDGA caused a dose dependent increase in the tensile strength and stiffness of the type I collagen fibers. A second treatment with NDGA improved the tensile properties significantly. Comparison of the effects of NDGA with those of biologically relevant mono-catechols indicated that the bi-catechol functionality of NDGA was responsible for generation of the superior tensile properties. Elimination of unreacted intermediates from the treated fibers with ethanol increased the effectiveness of the cross-linking process while simultaneously sterilizing the material. Catalyzing oxidation by saturating the reaction buffer with oxygen increased the effectiveness of polymerization and the resulting tensile properties of the treated fibers. The ultimate tensile strength of the optimized NDGA-treated fibers averaged 90 MPa; the elastic modulus of these fibers averaged 580 MPa. Both values are comparable to native tendon. The material properties of the NDGA cross-linked fibers exceed the properties of collagen fibers treated with other cross-linking strategies such as glutaraldehyde and carbodiimide. These results indicate that NDGA cross-linking may provide a viable approach to stabilizing collagenous materials for use in repair of ruptured, lacerated or surgically transected tendons, as well as other biomaterial constructs for surgical repair of musculoskeletal injuries and disease. PMID- 11762840 TI - Silicon excretion from bioactive glass implanted in rabbit bone. AB - Bioactive glass granules were implanted in the tibiae of rabbits in order to determine the pathway of the silicon released from bioactive glass in vivo. We traced and quantified the silicon released by obtaining 24-h urine samples and blood samples for up to 7 months after implantation. Bone tissue as well as the following organs were resected for chemical and histopathological analyses: kidney, liver, lung, lymph nodes, and spleen. The urinary silicon of the implanted group was significantly higher than in the control group. From the data, the calculated average excretion rate was approximately 1.8 mg/day, and as such, the amount of implanted silicon was excreted within statistical bounds in 24 weeks. At this point, only elevated concentrations of silicon were found at the implant site and not in the other organs. The concentrations of silicon measured in the urine were well below saturation. Since no significant increase in silicon was found in any of the organs including the kidney, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine. PMID- 11762841 TI - Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence. AB - In order to elucidate design principles for biocompatible materials that can be created by in situ transformation from self-assembling oligopeptides, we investigate a class of oligopeptides that can self-assemble in salt solutions to form three-dimensional matrices. This class of peptides possesses a repeated sequence of amino acid residues with the type: hydrophobic/negatively charged/hydrophobic/positively-charged. We systematically vary three chief aspects of this sequence type: (1) the hydrophobic side chains: (2) the charged side-chains: and (3) the number of repeats. Employing a rheometric assay to judge matrix formation, we determine the critical concentration of NaCl salt solution required to drive transformation from viscous state to gel state. We find that increasing side-chain hydrophobicity decreases the critical salt concentration in accord with our previous validation of DLVO theory for explaining this self assembly phenomenon Caplan et al. (Biomacromolecules 1 (2000) 627). Further, we find that increasing the number of repeats yields a biphasic dependence-first decreasing, then increasing, the critical salt concentration. We believe that this result is likely due to an unequal competition between a greater hydrophobic (favorable) effect and a greater entropic (unfavorable) effect as the peptide length is increased. Finally, we find that we can use this understanding to rationally alter the charged side-chains to create a self-assembling oligopeptide sequence that at pH 7 remains viscous in the absence of salt but gels in the presence of physiological salt concentrations, a highly useful property for technological applications. PMID- 11762842 TI - Subcutaneous microfabricated surfaces inhibit epithelial recession and promote long-term survival of percutaneous implants. AB - The long-term success of percutaneous devices is compromised by problems such as infection, mechanical avulsion and epithelial downgrowth. The objective of this study was to test the effects of microfabricated surfaces on tissue integration and long-term survival of percutaneous implants, using a modified implant design and a two-stage surgical method. Hexagonal titanium-coated epoxy implants were constructed with separate subcutaneous and percutaneous components, so that the effects of surface topography on connective tissue could be separated from the effects on epithelium. Subcutaneous components with 30-microm-deep micromachined grooves, 120-microm-deep tapered pits, or smooth control surfaces were secured to the calvarial bone of rats by a titanium pin. After 8 weeks, a percutaneous smooth-surfaced component was secured to the subcutaneous component. Dental impression materials were used to make models of the components and adjacent tissues at weekly intervals and tissue recession around the implants was measured. Some implants were removed at intervals up to 24 weeks and processed for histology. Connective-tissue ingrowth and mineralized tissue were noticed on the micromachined surfaces, whereas a thick capsule and epithelial downgrowth were observed on smooth control surfaces. On all implants, recession occurred most rapidly in the first 3 weeks, but was significantly reduced relative to the smooth controls only on implants with micromachined grooved subcutaneous surfaces (p<0.05). In addition, the time before failure was significantly (p<0.05) longer for implants with grooved subcutaneous surfaces than implants with smooth and pitted subcutaneous surfaces. This study indicated that an impression technique could be used to monitor tissue recession on percutaneous devices, and that micromachined grooved surfaces located subcutaneously improved the performance and longevity of percutaneous devices by promoting tissue integration. PMID- 11762843 TI - Comparison of the effects of Mg(OH)2 and sucrose on the stability of bovine serum albumin encapsulated in injectable poly(D,L-lactide-co-glycolide) implants. AB - Incomplete release and poor stability of encapsulated proteins are common hurdles to overcome when developing poly(lactide-co-glycolide) (PLGA) controlled-release systems. Antacid excipients such as Mg(OH)2, which increase both microclimate pH and polymer water uptake, have been shown to prevent acid-induced instability of proteins encapsulated in PLGA. The purpose of this study was to delineate the effects of microclimate pH and polymer water content on the stability of encapsulated bovine serum albumin (BSA) by comparing the effects of Mg(OH)2 with those of another excipient, sucrose, which increases polymer water content without significantly affecting acid-base chemistry of the polymer. These two excipients, when encapsulated in PLGA at appropriate levels (3% Mg(OH)2 vs. 10% sucrose), were found to cause identical water sorption kinetics, thus allowing the effect of the two microclimate parameters to be determined. In contrast to their similar effects on polymer water sorption, Mg(OH)2 afforded a much greater stabilization effect on encapsulated BSA than did sucrose, with less than 7% aggregates for 3% Mg(OH)2 compared to 51% for 10% sucrose and 81% without either excipient after 4 weeks of incubation at 37 degrees C. When the protein stabilization rationale of neutralizing the acidic microenvironment by adding Mg(OH)2 was applied to the delivery of an important therapeutic protein, tissue plasminogen activator (t-PA), t-PA stability was also improved and the active protein was completely recovered during a one month period of in vitro release. These data demonstrated that although increased water uptake induced by antacid excipients may improve the stability of the encapsulated proteins, the homogeneous acid neutralization effect is unique to antacid excipients such as Mg(OH)2, which is necessary to maintain the stability of proteins in acidic PLGA specimens. PMID- 11762844 TI - A method for evaluating the influence of porosity on the early reactions of blood with materials. AB - A method is presented for evaluating the influence of porosity on the early reactions of blood with polymer membranes of cellulose acetate and polyethersulfone with two different pore sizes, 0.1-0.2 microm and 0.8 microm. A system of two phases consisting of capillary blood and Dulbecco's phosphate buffered saline was constructed. Platelet adhesion and exposure of thrombospondin was examined by immunofluorescence. Platelet adhesion was higher on the membrane with 0.8 microm pore size. Leukocyte adhesion and viability was measured by fluorescein diacetate/propidium iodide staining, and the respiratory burst response to PMA and opsonized zymosan was measured by chemiluminescence. Leukocyte viability was higher on the membranes with 0.8 microm pore size and higher on the cellulose membrane for exposures upto 2 h. After 3 h the leukocyte viability was highest on the polyethersulfone membrane with a pore size of 0.8 microm. The respiratory burst response of membrane-adhering leukocytes could not be triggered by opsonized zymosan on any of the tested membranes. A response was seen after stimulation with PMA of cells adhering to the cellulose membrane with a pore size of 0.8 microm. PMID- 11762845 TI - Synthesis, characterization and platelet adhesion of segmented polyurethanes grafted phospholipid analogous vinyl monomer on surface. AB - New segmented polyurethanes (SPUs) grafted phospholipid analogous vinyl monomer, 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) on surface were synthesized. The soft segment of these polyurethanes was hydroxylated poly(isoprene) diol and the hard segments were 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD). SPUs were hydroxylated by potassium peroxodisulfate and MPC was grafted on the surface of hydroxylated SPUs using di-ammonium cerium (IV) nitrate (ceric ammonium nitrate, CAN) as a radical initiator. The bulk characterization of synthesized SPUs was investigated by infrared spectroscopy (IR) and gel permeation chromatography (GPC). The existence of phospholipid analogous groups on the surface of these SPUs was revealed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The surfaces of MPC-grafted SPUs showed decreased water contact angles compared to non-grafted SPU and the presence of phosphorylcholine groups. The blood compatibilities of the new polymers were evaluated by platelet rich plasma (PRP) contact studies and viewed by scanning electron microscopy (SEM) using BioSpan and non-grafted polyurethane as references. We found that fewer platelets adhered to the MPC-grafted surfaces and that they showed less shape variation than the references. These results suggest that these grafted polymers may have the possibility of the usage for biomaterials. PMID- 11762846 TI - Production of ordered collagen matrices for three-dimensional cell culture. AB - The aim of this study was to produce collagen gels with controlled fibrillar order as matrices for cell culture. Their structural characterization and colonization by human dermal fibroblasts arc presently reported. Ordered matrices are obtained by using the property of type I collagen monomers to self-assemble in liquid crystalline arrays by slow evaporation of acidic solutions at high concentrations. Induction of fibrillogenesis concomittent with the stabilization of the supramolecular order is then obtained, within petri dishes, by gelation of the viscous preparations under ammoniac vapours. For comparison, dermal equivalents, in which collagen compaction depends on fibroblasts contraction, are made according to the method of Bell et al. (Proc. Natl. Acad. Sci. 76(3) (1979) 1274). The fibrillar arrangement of the collagen network in the samples is determined by polarizing optical microscopy and by transmission electron microscopy. Whereas dermal equivalents exhibit heterogeneous distributions of fibrils, two differents types of order are obtained in the stabilized liquid crystalline collagen samples, namely aligned, i.e. nematic, at 20 mg/ml, or crimped, i.e. precholesteric, at 40 mg/ml. The morphology and behaviour of fibroblasts seeded on the surface of the matrices are analysed from day 1 to day 21. The cells are viable, proliferate at the surface of ordered matrices and migrate up to 400 microm in depth. Production of concentrated and ordered collagen matrices provides new perspectives to study the behaviour of cells in a valorized three-dimensional context where the fibrillar organization becomes close to in vivo situations. PMID- 11762847 TI - The effect of virtual cross linking on the oxidative stability and lipid uptake of aliphatic poly(urethane urea). AB - In vitro oxidative degradation and lipid sorption of aliphatic, low elastic modulus and virtually cross-linked poly(urethane urea)s based on 4,4' methylene bis(cyclohexyl isocyanate), hydroxy terminated poly butadiene and hexamethylene diamine were evaluated. The aged samples revealed no weight loss in the oxidation medium. The IR spectral analyses revealed the stability of unsaturated double bonds at 964 cm(-1) (characteristic for polybutadiene soft segment) with no change in peak intensity. The poly(tetramethylene glycol) (PTMG)-added poly(ether urethane urea) polymer also revealed no disappearance of IR peaks for ether and unsaturated double bonds in samples aged in vitro oxidation medium. All the polymers have shown increase in weight due to lipid up take in lipid-rich medium (palm oil) but it was rather low in Dulbecco's modified eagle medium (DMEM) cholesterol. The slight change in mechanical properties of the present polymers in oxidation and DMEM is due to the rearrangement of molecular structure with virtual cross links of hydrogen bonding (physical cross linking) without degradation and plasticization effect of lipid. The influence of these media on the rearrangement of virtual cross links has been observed. Higher the virtual cross-link density, lesser is the loss of tensile properties of poly(urethane urea)s in the oxidation medium and vice versa. On the other hand, higher the virtual cross-link density of poly(urethane urea), higher is the loss of ultimate tensile strength and stress at 100% strain and vice versa in DMEM medium. PMID- 11762848 TI - In vitro degradation of Polyactive 1000PEOT70PBT30 devices. AB - Polyactive 1000PEOT70PBT30 (a segmented block copolymer of poly(ethylene oxide terephtalate)/poly(butylene terephtalate) with 70/30 PEOT/PBT ratio) was processed into three different types of samples: injection molded to rods, hot pressed to films and to composite membranes made by hot-pressing a tubular mesh of poly-L,D-lactide 96/4 between two films of Polyactive. The molecular weight of Polyactive was not influenced by processing, but gamma-sterilization seemed to increase the weight average molecular weight (Mw). Mechanical properties of the rods and films decreased rapidly in hydrolytic conditions due to the hydrogel nature of the polymer, swelling and degradation. Mesh reinforcement increased the mechanical properties, but the components separated during soaking. In vitro the molecular weight of the rods and films started to decrease immediately, but the PEOT (or PEO) proportion remained relatively constant for 26 weeks. Macroscopically, all the wet devices remained intact, but fragmented on drying. Microscopically, topographical formations of polymer were found on the surfaces and small sodium-rich spots were precipitated onto and inside the polymer. Thermal measurements showed that polymer consisted of amorphous PEOT segments and both amorphous and crystalline PBT segments. PMID- 11762849 TI - Effect of load on the early incorporation of impacted morsellized allografts. AB - Impacted morsellized bone grafts are clinically successful to restore bony defects after failed total hip arthroplasties. The incorporation process seems to be dependent on the location where the reconstruction is performed, which suggests that load could play a role. In this study, we hypothesised that, as in fracture healing, physiological loading has a stimulatory effect on the process of early bone graft incorporation. To test this hypothesis we created a standardised defect in the distal femur of twelve goats. Allograft bone chips were impacted into the defect and a subcutaneous pressure implant was screwed in. With this implant the graft can be loaded under controlled circumstances. Six goats were subjected to a daily loading regime of 3 MPa, the other six were non loaded. After five weeks the bone mineral density was measured with peripheral quantitative computer tomography. Thereafter, routine histology and histomorphometry were carried out. Bone mineral density was not affected by load. Histology revealed microscopic evidence of bone graft incorporation, which proceeded in a similar way in both loaded and non-loaded specimens. New bone was formed free in the stroma or on graft remnants after osteoclastic resorption of the graft. Only the area of active incorporating bone graft was higher under load. In conclusion, the formation of a new bony structure was not affected by load after five weeks. However, load resulted in a larger area of active graft incorporation at this early stage. Possibly biological and immunological factors govern the early incorporation process independent of the local loading regime. PMID- 11762850 TI - Effect of four acrylic bone cements on transforming growth factor-beta1 expression by osteoblast-like cells MG63. AB - Based on the hypothesis that bone cements cause changes in the production of transforming growth factor-beta 1 (TGF-beta1) by bone cells, the effects of four acrylic bone cements (Sulfix-60, CMW 1, CMW 2 and CMW 3) were examined using the osteoblast-like cell line MG63. The extracts in MEM of the cements were tested, following 1 h- and 7 day-curing. MG63 cells seldom expressed mRNA specific for TGF-beta1 in basal conditions. The cultures expressed mRNA constantly after incubation with the extract of CMW 1 cured for 1 h. TGF-beta1 specific mRNA was seldom expressed after incubation with the other cement extracts. The release of TGF-beta1 into the conditioned medium was increased significantly by CMW 1 extract at 1 h-curing, but was not changed significantly by CMW 1 extract at 7 day-curing and by the extracts of the other cements, at both curing times. The stimulating effect of CMW 1 on the secretion of TGF-beta1, even with all the restrictions of an in vitro study of continuous cell lines, if confirmed in vivo, might favor the development of the synovial-like membrane around the implant, and therefore impair the chance of success of the prosthesis. PMID- 11762851 TI - Apatite formation on zirconium metal treated with aqueous NaOH. AB - Previous studies by the authors have shown that titanium metal, titanium alloys and tantalum metal which were subjected to aqueous NaOH solution and subsequent heat treatments form an apatite surface layer upon immersion in a simulated body fluid (SBF) with ion concentrations nearly equal to those in human blood plasma. These metals form the apatite surface layer even in living body, and bond to living bone through the apatite layer. In the present study, the apatite-forming ability of NaOH-treated zirconium metal in SBF has been investigated. A hydrated zirconia gel layer was formed on the surface of the zirconium metal on exposure to 1-15 M NaOH aqueous solutions at 95 degrees C for 24h. It was observed that the metals treated in NaOH aqueous solutions with concentrations above 5 M form an apatite layer on their surface in SBF. This indicates that the Zr-OH group of the zirconia gel induces apatite nucleation. The present study points to the possibility of obtaining bioactive zirconium after treatment by NaOH. PMID- 11762852 TI - Spark plasma sintering of hydroxyapatite powders. AB - Dense hydroxyapatite (HA) compacts have been successfully fabricated by a spark plasma sintering (SPS). The sintering behavior of HA powders at different temperatures ranging from 850 degrees C to 1100 degrees C was studied. Results showed that spark plasma sintering resulted in rapid densification to near theoretical density. The HA compact was homogeneously sintered at 950 degrees C in a short sintering duration of 5 min, while maintaining high quality and high relative density (>99.5%). The density, microhardness and Young's modulus of HA sintered compact initially increased with the sintering temperature, reached a maximum value at around 950-1000 degrees C, then decreased with further increase in the temperature due to the decomposition of HA into beta-tricalcium phosphates. Fracture toughness results showed no significant difference with increasing temperature due to the combined influences of density and grain size. Microstructure analysis showed no noticeable grain growth under different sintering temperatures due to the short time exposure at high temperatures. PMID- 11762853 TI - Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness. AB - The development of flexible polyurethane heart valves has been hindered by material degradation in vivo. Low modulus polyurethane leaflets are regarded as desirable to achieve good hydrodynamic function. However, low modulus materials may suffer high strain accumulation, hence poor durability. Higher modulus materials may improve durability, but may have poor hydrodynamic function. This study examines the hydrodynamic behaviour of biostable polyurethane valves, varying Young's modulus from 5 to 63.6 MPa and mean leaflet thickness from 48-238 microm. Parameters studied included mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.61 min( 1)) At low cardiac output, modulus was not significantly correlated with any parameter of valve opening. At 9.61 min(-1), modulus significantly influenced mean pressure gradient (p = 0.033). Mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow at all cardiac outputs (p<0.001). This study demonstrates that, over a wide range of moduli, valve hydrodynamic function is not affected significantly by the material modulus. Leaflet thickness is a highly significant factor. Higher modulus elastomers in a range up to 32.5 MPa may be useful in prosthetic heart valve leaflet manufacture, retaining good hydrodynamic function while potentially extending the lifetime of the valve. PMID- 11762854 TI - The effect of Nd:YAG radiation at nanosecond pulse duration on dentine crater depth. AB - The effect of laser parameters on laser-dentine interaction is little known. The aim of this in vitro study was to determine the effect on dentine crater depth of Nd:YAG laser radiation in relation to pulse repetition rate, total delivered energy, dentine site and the presence or absence of a dye. One hundred and forty four sound third molars were extracted and sectioned transversely to provide 288 upper and lower cut surfaces. The upper surfaces were painted with a layer of dye (IR5) suitable for absorption at 1064 nm. The specimens were divided into 12 sub groups each containing 12 upper and 12 lower specimens. These were exposed to a Nd:YAG laser with a 30 nanosecond (ns) pulse duration. This laser operated in a non-contact mode (spot diameter 165 microm) with pulse repetition rates of 2.5, 5.4 and 10.5 Hz. Four total energies were delivered at each repetition rate; 2.3, 3.63, 3.96, 4.29 joule (J) at 2.5 Hz repetition rate; 2.3, 2.64, 3.63, 4.29 J at 5.4 and 10.5 Hz repetition rates. Five outer and three inner sites were irradiated on each specimen. Each dentine crater depth was measured five times using a Reflex Microscope and a three-dimensional centre of gravity derived. An upper and lower specimen were taken from each sub-group and viewed under a scanning electron microscope (SEM). ANOVA was applied: total delivered energy and dyed/undyed were found to have a statistically significant effect on crater depth (p<0.0001). In general increasing energy and the presence of dye produced deeper craters. Inner/outer dentine location and repetition rate were not found to be statistically significant. All craters were carbonised. PMID- 11762856 TI - Assessment and characterization of degradation effect for the varied degrees of ultra-violet radiation onto the collagen-bonded polypropylene non-woven fabric surfaces. AB - Exposure to ultra-violet (UV)-C radiation is a frequently used method to prevent bacteria from invasion of blood-contact biomedical products. Potential damage induced by UV radiation to collagen is of concern due to the decay of bioactivity, considerably correlated with structural alterations. Our current investigation studies the collagen-bonded non-woven polypropylene (PP) fabric surface. In this experiment, antenna-coupling microwave plasma is utilized to activate PP fabric and then the sample is grafted with acrylic acid (AAc). Type III collagen is immobilized by using water soluble 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide as coupling agent. The collagen-bonded samples with sample temperature ca. 4 degrees C are then exposed to UV-254nm radiation for different time intervals. By using fourier-transformed infrared with attenuated total reflection (FTIR-ATR) and XPS (X-ray photoelectron spectroscopy), we examine the chemical structures of samples with different treatments. Coomassie brilliant blue G250 method is utilized to quantify the immobilized collagen on the PP fabric surfaces. Blood-clotting effects are evaluated by activated partial thromboplastin time, thrombin time, and fibrinogen concentration tests. By means of cell counter and scanning electron microscopy we count red blood cells and platelets adhesion in the modified porous matrix. Our experimental results have demonstrated that with pAAc-grafting of ca. 173 microg cm(-2) and immobilized collagen of 80.5+/-4.7 microg cm(-2), for human plasma incubated samples of various intervals of UV-254 nm radiation, fibrinogen concentration decreases in human plasma, while platelets and red blood cells adhesions increase before UV radiation. However, the required time for thrombination shows significant change for UV radiation exposure of less than 20 h (alpha = 0.05). The decay of bioactivity for the UV-irradiated, collagen-bonded surfaces is thus evaluated. Surface analyses indicate that the decrease of R-COOH (derivated from grafted-pAAc or de-carboxylation of collagen), amides degradation (broken-NH), and phenylalanine scission (terminated by -OH, tyrosine formation) may gradually damage collagen by increasing the intervals of UV radiation. These effects considerably influence the bioactivity of the collagen-bonded fabric. The XPS measurements of C 1s core levels at 288.4 eV (O = C-NH) and at 289.1 eV (O = C-O) illustrate significant decreases of intensity after radiation time ca. 44 h. It is clear that UV-254 nm radiation exposure for ca. 20 h has the potential impact to moderate the bioactivities of collagen and therefore act as a vital factor to accelerate biodegradation. PMID- 11762855 TI - Effects of fluoride concentration and elastic tensile strain on the corrosion resistance of commercially pure titanium. AB - The corrosion resistance of commercially pure (CP) titanium in 1% NaCl + 0 approximately 1% NaF solution (pH = 6) under different elastic tensile strains was investigated by using electrochemical impedance spectroscopy (EIS) measurement technique. The polarization resistance (Rp), which is inversely proportional to the corrosion rate, of CP titanium in the test solution was obtained from the EIS data. Different elastic tensile strains, namely 0%, 1%, 2%, and 4%, were applied on the test specimens by using a tensile test machine during the corrosion tests. Corrosion morphology was characterized by using a scanning electron microscope. Surface chemical analyses were performed by using energy dispersive spectroscopy and X-ray photoelectron spectroscopy. The results showed that the NaF concentration and the elastic tensile strain had a statistically significant influence on the Rp (P<0.001). The Rp decreased on increasing the NaF concentration and the elastic tensile strain. When the NaF concentration was lower than 0.10%, the Rp value (> 3.4 x 10(5) omega cm2) was mainly ascribed to the formation of a protective titanium dioxide (TiO2) on the metal surface, regardless of the elastic tensile strain applied. However, when the NaF concentration was higher than 0.1%, the protectiveness of TiO2 was destroyed by fluoride ions, leading to severe corrosion of CP titanium. PMID- 11762857 TI - The biocompatibility evaluation of epoxy resin-based root canal sealers in vitro. AB - The cytotoxic and mutagenic effects of epoxy resin-based root canal sealer AH26 and AH-Plus were determined in vitro. Root canal sealers were eluted for 24 h in dimethyl sulfoxide (DMSO) and diluted in culture medium. Cytotoxic effects were assessed using the MTT [tetrazolium dye, 3-(4.5-dimethylthiazol-2-yl)-2.5 diphenyltetrazolium bromide, C18H16N5SBr] assay for mitochondrial enzyme activity and also the cell viability. Genotoxicity assays were assessed using the alkaline single cell gel electrophoresis assay (comet assay) for DNA damage measurement. Result indicated that both the AH26 and AH-Plus sealers exhibited a dose dependent increase in astrocyte toxic effects. Additionally, dose-dependent astrocyte DNA damage was also noted for both sealers. Therefore, these epoxy resin-based sealers, AH26 and AH-Plus demonstrated both cytotoxicity and genotoxicity in vitro. PMID- 11762858 TI - Titanium dioxide reinforced hydroxyapatite coatings deposited by high velocity oxy-fuel (HVOF) spray. AB - Hydroxyapatite (HA) coatings with titania addition were produced by the high velocity oxy-fuel (HVOF) spray process. Mechanical properties of the as-sprayed coatings in terms of adhesive strength, shear strength and fracture toughness were investigated to reveal the effect of the titania reinforcement on HA. Qualitative phase analysis with X-ray diffraction (XRD) showed that mutual chemical reaction between TiO2 and HA, that formed CaTiO3 occurred during coating formation. Differential scanning calorimetry (DSC) analysis of the starting powders showed that the mutual chemical reaction temperature was approximately 1410 degrees C and the existence of TiO2 can effectively inhibit the decomposition of HA at elevated temperatures. The positive influence of TiO2 addition on the shear strength was revealed. The incorporation of 10 vol% TiO2 significantly improved the Young's modulus of HA coatings from 24.82 (+/- 2.44) GPa to 43.23 (+/- 3.20) GPa. It decreased to 38.51 (+/- 3.65) GPa as the amount of TiO2 increased to 20 vol%. However, the addition of TiO2 has a negative bias on the adhesive strength of HA coatings especially when the content of TiO2 reached 20 vol%. This is attributed to the weak chemical bonding and brittle phases existing at the splats' interface that resulted from mutual chemical reactions. The fracture toughness exhibited values of 0.48 (+/- 0.08) MPa m0.5, 0.60 (+/- 0.07) MPa m0.5 and 0.67 (+/- 0.06) MPa m0.5 for the HA coating, 10 vol% TiO2 blended HA coating and 20 vol% TiO2 blended HA coating respectively. The addition of TiO2 in HA coating with the amount of less than 20 vol% is suggested for satisfactory toughening effect in HVOF HA coating. PMID- 11762859 TI - Experimental procedure for the evaluation of the mechanical properties of the bone surrounding dental implants. AB - The mechanical stability of the fixture in bone is one of the most important factors for the long-term reliability of dental implants. This paper focuses on an experimental procedure to evaluate the mechanical properties of the bone surrounding dental implants. The procedure is based on a surgical animal model followed by mechanical tests. The experimental mechanical testing has been used for preliminary investigations on the role played by different parameters such as the healing time and the surgical technique (standard or with regenerative material). The procedure has been evaluated in some preliminary tests on a few specimens. Microradiographic analyses have been performed on the bone surrounding the implants in order to give an interpretation of the bone properties on the basis of the bone morphology and to distinguish the newly formed bone from the pre-existing bone. The preliminary results relevant to 10 threaded titanium implants are presented and discussed. Our findings show that the mechanical properties of the bone surrounding the implant improve with the increase in the healing time from 24 to 45 days. The ultimate loads recorded during mechanical tests arise from 395 N to 2665 N in case of coronal defects filled with bone regenerative and from 2200 N to 5700 N in case of standard technique. PMID- 11762860 TI - Microabrasion--a simple method to assess surface degradation of UHMWPE following sterilisation and ageing. AB - The ageing behaviour of ultra-high molecular weight polyethylene (UHMWPE) has been studied following gamma irradiation (25 or 40 kGy) in air. Accelerated ageing procedures used elevated temperature (70 degrees C) and/or pressurised oxygen (5bar). Shelf-aged UHMWPE was also studied. The variation in surface density and mechanical properties were determined following the various sterilisation and ageing treatments. Microabrasive wear testing was also performed. Wear rates were found to correlate well with stress at break for sterilised and aged UHMWPE but not with elongation to failure. It is proposed that the wear mechanism is fracture dominated and occurs following some disentanglement of the polymer chains. Wear also depends upon embrittlement of the surface layer due to its processing and ageing. Elongation to failure in a tensile test is not a good measure of this embrittlement whereas the microabrasion test provides more surface sensitive information concerning this property. PMID- 11762861 TI - 'They all look alike to me': prejudice and cross-race face recognition. AB - We investigated whether prejudice level influences the size of the other-race effect (poorer recognition of other-race compared with own-race faces). Previous studies, using self-report measures of prejudice, failed to find a relationship between prejudice and the other-race effect. We used an implicit prejudice measure, developed by Fazio, Jackson, Dunton, and Williams (1995), to determine whether implicit prejudice influences the size of the other-race effect. A self report measure of prejudice, Walker's (1994) Attitudes to Asians Scale, was also included to replicate previous results. A group of 30 high prejudice and 30 low prejudice Caucasian participants, as determined by the self-report measure, were run through a procedure which assesses implicit prejudice and recognition performance at the same time. Neither implicit nor self-reported prejudice level influenced the size of the other-race effect. Unexpectedly, implicit and self report prejudice influenced (in opposite ways) recognition of own-race faces. The implications of these results for understanding the other-race effect are discussed. PMID- 11762862 TI - Investigating the role of context in learning to read: a direct test of Goodman's model. AB - The much discussed 'whole language' or 'real books' approach to children's reading is based on a theory which makes two quite separate predictions: (1) that children will read difficult words more successfully in context than in isolation, and (2) that contextual experience of words will lead to greater improvements in word reading than isolated experience of words. We report a study which tests both predictions and supports the first but not the second. PMID- 11762863 TI - The effects of irrelevant speech and articulatory suppression on the serial recall of silently presented lipread digits. AB - The immediate serial recall of lipread material is disrupted by irrelevant speech (Campbell & Dodd, 1984; Jones, 1994) and by articulatory suppression (Campbell & Dodd, 1984). However, the interaction between these has not been directly examined. In Exp 1, participants recalled silently presented lipread digits in conditions of quiet, irrelevant speech, articulatory suppression and suppression/speech combined. Irrelevant speech disrupted recall, but not when articulation was suppressed. Experiment 2 demonstrated that participants were able to accurately lipread targets in all of the above experimental conditions. A third experiment contrasted predictions derived from the phonological loop model (PL; Baddeley, 1986) and the changing state hypothesis (CSH; Jones, 1993). The CSH predicts that tones and speech that vary in frequency to the same degree will disrupt recall equally (Jones & Macken, 1993), whereas the PL model implies that speech will always be more disruptive. The results support the CSH, and extend the findings of Jones and Macken (1993) to account for lipread stimuli. As with graphic presentation, the CSH provides a better account of the processes underpinning the irrelevant speech effect; however, it is argued that the recoding hypothesis from the PL model should be retained. PMID- 11762864 TI - Earwitness testimony: effects of exposure and attention on the face overshadowing effect. AB - Two experiments tested memory for a once-heard voice. Experiment 1 showed that hearing an unknown voice utter the same sentence three times improved recognition of the voice a week later compared with hearing only a single utterance of the sentence, but instructions to attend to the voice did not. The impairment caused by seeing the speaker's face during the original utterance (the Face Overshadowing Effect--FOE) occurred only with the single utterance and was unaffected by instructions. It was concluded that length of utterance without increase in speech variety aids voice recognition, and that the FOE is not due to voluntary attention to face rather than voice, but may be due to involuntary attention to the initial exposure of the face. Experiment 2 investigated whether exposure to the face before the onset of speech reduced the FOE. Such an effect was observed and it was concluded that the FOE is due to involuntary preference for processing face information in order to aid later recognition of the individual, while speech is processed primarily for meaning. Absence of an FOE on memory for the words uttered was consistent with this interpretation. PMID- 11762865 TI - On the psychology of drinking: being thirsty and perceptually ready. AB - The present research is concerned with cognitive effects of habitually regulated primary motives. Specifically, two experiments tested the idea that feelings of thirst enhance the cognitive accessibility of, or readiness to perceive, action relevant stimuli. In a task allegedly designed to assess mouth-detection skills, some participants were made to feel thirsty, whereas others were not. Results showed that participants who were made thirsty responded faster to drinking related items in a lexical decision task, and performed better on an incidental recall task of drinking-related items, relative to no-thirst control participants. These results suggest that basic needs and motives, such as thirst, causes a heightened perceptual readiness to environmental cues that are instrumental in satisfying these needs. PMID- 11762866 TI - Illusions in reading maps by touch: reducing distance errors. AB - The study reports systematic distance errors in reading raised-line maps by touch, and how they can be reduced. We show that T-shaped road junctions produce the typical error due to overestimating the length of the bisecting road compared to the bisected road. The error was not reduced when the target location was marked initially by a symbol. However, it was eliminated by instructions to use both hands concurrently to scan the route relative to an external square frame surrounding the map layout and to the body midline. Road junctions, which resemble 'Muller-Lyer' configurations, produced a significant overestimation of the length of a road that ended in diverging side roads relative to underestimating a road section with converging side roads. Spatial anchor cues from landmarks along the route, either alone or in conjunction with the spatial frame instructions, eliminated the illusion equally. We discuss theoretical implications, and the use of map frames and landmarks as spatial guides to improve map use by touch. PMID- 11762867 TI - Locus of control and health behaviour revisited: a multivariate analysis of young adults from 18 countries. AB - The inconsistent and small associations between health locus of control and health behaviour found in previous studies may be due to the use of small samples, and an overreliance on correlations as measures of association. We assessed relationships between internal powerful others and chance health locus of control, health values, and ten health-related behaviours (physical exercise, smoking, alcohol consumption, breakfast, tooth-brushing, seat belt use, and consumption of fruit, fat, fibre and salt) in 4358 female and 2757 male university students from 18 European countries. Multivariate logistic modelling, assessing the odds of engaging in healthy behaviour with graded changes in locus of control, identified substantial associations. For five behaviours, the odds of healthy behaviour were more than 40% greater among individuals in the highest vs. lowest quartile of internal locus of control after adjustment for sex, age, health value and other locus of control scales. High chance locus scores were associated with more than 20% reductions in the likelihood of healthy options for six behaviours, while powerful others scores showed more variable associations with healthy actions. Inclusion of health value within the analyses did not change the nature of the relationships observed between variables. Associations between health locus of control and health behaviour are of a similar magnitude to other psychosocial factors when appropriate statistical tests are employed. PMID- 11762868 TI - Bullying and victimization of primary school children in England and Germany: prevalence and school factors. AB - Differences in definitions and methodologies for assessing bullying in primary school children between countries have precluded direct comparisons of prevalence rates and school factors related to bullying. A total of 2377 children in England (6-year-olds/Year 2: 1072; 8-year-olds/Year 4: 1305) and 1538 in Germany (8-year olds/Year 2) were questioned individually using an identical standard interview. In both countries the types of bullying to victimize others were similar: boys were most often perpetrators, most bullies were also victims (bully/victims), most bullying occurred in playgrounds and the classroom, and SES and ethnicity only showed weak associations with bullying behaviour. Major differences were found in victimization rates with 24% of English pupils becoming victims every week compared with only 8% in Germany. In contrast, fewer boys in England engaged every week in bullying (2.5-4.5%) than German boys (7.5%), while no differences were found between girls. In England, children in smaller classes were more often victimized. Further study of the group of bully/victims, schooling differences in England vs. Germany and implications for prevention of bullying are discussed. PMID- 11762869 TI - Gingival recession defects and guided tissue regeneration: a review. AB - The last decade has seen an increasing number of clinical reports on guided tissue regeneration (GTR) for reconstruction of gingival recession defects. This article reviews the value of GTR in the management of gingival recession defects based on records from such reports. Studies and case-series using nonresorbable and bioresorbable membranes, studies comparing GTR to the subepithelial connective tissue graft (CTG) procedure, and histologic reports of healing following GTR, published in the English language from 1985 to 2000, were identified using a Medline search and were included in the data-base for this review. The Following pre- and post-treatment data were collated and evaluated for each of the reports: gingival recession depth, probing depth, clinical attachment level, and width of the keratinized gingiva. In perspective of the limitations of the studies reviewed, it has been shown that GTR may be used for reconstruction of gingival recession detects. Importantly it has not been shown that GTR provides an added clinical benefit for the patient treatment planned for reconstruction of gingival recession defects. i.e. GTR does not appear to offer a significant advantage over mucogingival procedures such as the connective tissue graft or the advanced flap procedure. It is imperative to recognize inherent technical difficulties associated with GTR including primary would closure and secondary membrane exposure: membrane exposures being negatively correlated to desired clinical outcomes. Also, membrane exposures appear consistently more common in smokers than in non-smokers. It is also imperative to recognize shortcomings and adverse effects including space maintenance and unacceptable foreign body reactions associated with some bioresorbable GTR technologies. PMID- 11762870 TI - Effects of glucose on formation of cytotoxic end-products and proteolytic activity of Prevotella intermedia, Prevotella nigrescens and Porphyromonas gingivalis. AB - Black-pigmented bacteria which produce cytotoxic metabolic end-products and cell membrane-associated proteases have been reported to play an important role in the pathogenesis of periodontal diseases. These bacterial virulence factors can be modified by the environmental conditions including nutrients supplied variously into the oral cavity. Although glucose is one of the most essential nutrients for oral bacteria, the exogenous supply of glucose may be discontinuous and the glucose concentration in a periodontal pocket may be influenced by the depth of the periodontal pocket. Therefore, effects of glucose as an environmental factor on the virulence factors of Prevotella intermedia, Prevotella nigrescens and Porphyromonas in the presence o glucose.,bo t P. intermedia and P. nigrescens markedly decreased the production of cytotoxic end-products including succinate.,isobutyrate,isovalerate and ammonia, although their growth was increased. Furthermore, the proteolytic activities such as immunoglobulin- albumin- and casein-degrading activities of these bacteria were decreased in the presence of glucose. On the other hand, no effect of glucose on the metabolic activity of P gingivalis was observed. These results suggest that pathogenicity of P. intermedia P. nigrescens may be decreased by the presence of glucose. PMID- 11762871 TI - Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study. AB - The present study investigated the effect of nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. Twenty adult male Wistar rats were used. After anesthesia, a mandibular first molar was randomly assigned to receive a cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments. of daily intraperitoneal injections: A - saline solution, B -0.37 mg of nicotine kg, C -0.57 mg of nicotine kg and D 0.73 mg of nicotine/kg. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Statistical analysis (ANOVA) revealed greater bone loss (p<0.05) in the ligated teeth of animals which received nicotine (groups B/C D) than in the ligated teeth of animals which received saline solution (group A). In addition, a dose-dependent response was observed among the nicotine groups. A negative effect of nicotine was observed in the unligated teeth of the experimental groups (p<0.05). Therefore, daily administration of nicotine enhanced, in a dose-dependent manner, the effects of local factors in producing periodontal breakdown. Furthermore, the nicotine seemed to have a direct deleterious effect on the periodontal tissues. PMID- 11762872 TI - Enamel matrix derivative (EMDOGAIN) rapidly stimulates phosphorylation of the MAP kinase family and nuclear accumulation of smad2 in both oral epithelial and fibroblastic human cells. AB - In our previous study, we demonstrated that porcine enamel matrix derivative (EMD) induces p21WAF1/cip1 within 8 hours and subsequently arrests the cell cycle of human oral epithelial cells in G1 phase. In contrast, EMD markedly stimulates the proliferation of gingival fibroblasts without inducing p21WAF1/cip1. To investigate the mechanism of how EMD produces these differential effects, we have focused on the initial response of these two cell types to EMD. In epithelial cell cultures, EMD stimulated cytoskeletal actin polymerization within 30 min and promoted cell adhesion in our experimental system. EMD failed to stimulate either intracellular Ca2+ mobilization or cAMP production in either cell type. In both epithelial and fibroblastic cells, EMD (25-100 microgram/ml) rapidly produced dose-dependent phosphorylation of the mitogen-activated protein kinase (MAPK) family: extracellular signal response kinase (ERK), p38-MAPK (p38-K), and c-Jun terminal kinase/stress-activated protein kinase (JNK). However, neither inhibitors of MEK (ERK kinase) nor p38-K could block EMD's anti-proliferative action on epithelial cells. On the other hand, EMD rapidly stimulated translocation of smad2 into the nucleus in both cell types. Spurred by this finding, we assayed for TGF-beta1, a ligand for one receptor associated with smad2 activation, and detected significant levels in EMD preparations. The sum of these pharmacological findings indicates that EMD contains at least one bioactive factor, which is most probably TGF-beta1 (or TGF-beta-like substances). In conjunction with the similarities in the differential growth-modulating actions between EMD and what is known for TGF-beta, we suggest that TGF-beta might act as the principal growth regulating agent of oral fibroblastic and epithelial cell types in EMD despite being present in only low levels. PMID- 11762873 TI - Hepatocyte growth factor secreted by periodontal ligament and gingival fibroblasts is a major chemoattractant for gingival epithelial cells. AB - To ascertain whether periodontal fibroblasts could be involved in the pathogenesis of periodontal pocket formation, the chemotactic activity of periodontal ligament fibroblast-conditioned medium (PLF-CM) and gingival fibroblast-conditioned medium (GF-CM) for gingival epithelial cells was examined using a modified Boyden chamber assay. Both PLF-CM and GF-CM possessed significant chemotactic activity, which was decreased markedly by treatment with anti-human hepatocyte growth factor (HGF) neutralizing antibody. Furthermore, the chemotactic activity of PLF-CM and GF-CM was well correlated with HGF content. These results show that PLF and GF secrete an HGF-like factor, and suggest that such a factor derived from periodontal fibroblasts might play a role in epithelial apical migration in periodontitis. PMID- 11762874 TI - Morphometric evaluation of gingival overgrowth and regression caused by cyclosporin in rats. AB - Cyclosporin A is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Cyclosporin A can cause various side effects including gingival overgrowth. The aim of this work was to evaluate gingival overgrowth of rats treated daily with 10 mg/kg bodyweight of cyclosporin A for 60 days, as well as the regression after the interruption of treatment. All rats treated with cyclosporin A developed gingival overgrowth, with increased thickness of the epithelium, height and width of the connective tissue. The density of fibroblasts and collagen fibers also increased. Five to 90 days after the interruption of treatment with cyclosporin A, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblast densities. The reduction was more pronounced in the initial periods and after 90 days did not return to the normal values. PMID- 11762875 TI - Differential gene expression in neutrophils from patients with generalized aggressive periodontitis. AB - Differential gene expression was investigated in neutrophils stimulated with N formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive-P. n = 6), generalized chronic periodontitis (Chronic-P, n = 6) and healthy controls (H, n = 8). Our results show that 37 genes were upregulated. while 27 genes were down-regulated in all Aggressive-P neutrophils by using RAP-PCR with 45 primer pairs. Reverse transcription-PCR analyses revealed that mRNA levels were significantly different (p<0.05) for heat shock transcription factor 4b (HSF4b) gene. Kruppel-like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive-P compared to groups H and Chronic-P. Zf9 and muskelin genes were lower in Aggressive-P compared to the H groups, but no significant difference was noted compared to the Chronic-P group. The control genes, IL-1beta and VEGF genes, were expressed at a significantly higher level in Aggressive-P and Chronic-P than H (p<.01, p<0.05). In conclusion, the RAP-PCR technique used in this study enabled us to identify 3 Aggressive-P related genes, which had not been reported previously. Neutrophil functions in Aggressive-P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF-beta) and muskelin (cellular adhesion). PMID- 11762876 TI - Bacteroides forsythus prtH genotype in periodontitis patients: occurrence and association with periodontal disease. AB - Bacteroides forsythus has been described as a periodontopathogen and its presence in the subgingival plaque can lead to periodontal disease. Recently, a cysteine protease designated as prtH was isolated and characterized from B. forsythus ATCC 43037. The purpose of this study was to determine the prevalence and the association of the prtH gene of B. forsythus with periodontal disease. A total of 160 subgingival plaque samples were assayed with the polymerase chain reaction method using oligonucleotide primers targeting the prtH and the 16S rDNA genes of B. forsythus. Primers targeting the 16S rDNA gene of B. forsythus were used to determine the occurrence of the bacteria in the subgingival plaque samples at baseline. At baseline, B. forsythus was detected in 78 out of 86 (91%) diseased sites and 33 out of 74 (45%) healthy sites studied. Among the 86 diseased sites examined, 73 sites (85%) were colonized by the bacteria with the prtH genotype. In sites of the periodontally healthy, 7 out of 73 (10%) possessed B. forsythus with the prtH genotype. The results obtained suggested strong association of the prtH gene of B. forsythus with adult periodontitis. Although this bacterial species was detected from about half of the periodontally healthy samples, only a fraction of these subjects possess the bacteria strain with the prtH genetic subtype. We propose the use of the prtH gene as an alternative to the more widely used 16S rDNA gene of B. forsythus, for a more accurate determination of the prevalence of periodontal health and disease in epidemiological studies and clinical screening. PMID- 11762877 TI - Reflex and non-reflex elements of hypertonia in triceps surae muscles following acquired brain injury: implications for rehabilitation. AB - BACKGROUND: Following adult onset acquired brain injury, the triceps surae muscles tend to become shortened and exhibit increased resistance to passive lengthening; a phenomenon that has been termed 'hypertonia'. Spasticity (velocity dependent tonic reflex hyper-excitability) has traditionally been considered a major component of hypertonia. In addition, unmodulated descending excitatory influences on the alpha motorneurone pool may result in inappropriate or excessive muscle activity (dystonia). Non-reflex changes, secondary to the brain injury, and as a consequence of subsequent immobility, also take place in the passive and active elements of the muscle. These non-reflex changes affect the stiffness and extensibility of the musculo-tendinous unit. Atrophy of muscle fibres combines with collagen proliferation to produce increased muscle stiffness. This may be compounded by increased actin-myosin cross-bridge linkages, which are thought to be associated with reduced rates of cross-bridge detachment. Prolonged immobilization in a shortened position results in a loss of sarcomeres in series. Arthrogenic changes associated with disuse include remodelling of dense connective tissue and intra-articular adhesions. CONCLUSION: Decreased muscle extensibility may be exacerbated by muscle overactivity. Consideration of all of the potential factors contributing to hypertonia of the triceps surae muscle will assist clinicians to identify appropriate intervention strategies, which may facilitate better treatment outcomes. PMID- 11762878 TI - Determinants of chronic disability related to low back pain: towards an integrative biopsychosocial model. AB - PURPOSE: Since the early 1990s, numerous prospective studies have been published on the determinants of chronic disability related to low back pain (LBP) of non specific origin whose human and financial costs are enormous. The significant contribution of psychosocial factors is being increasingly recognized. However, additional efforts are needed to clarify their role and to improve the interventions. The purpose of this theoretical paper is to propose a coherent organization of the medical and psychosocial determinants identified in prospective studies into a conceptual framework. METHOD: Several models available in the field of pain and disability as well as in health psychology were reviewed. RESULTS: A recent version of the stress coping model was chosen and adapted to the problem. The adapted model suggests that stress, particularly that caused by the pain associated with LBP, could have a negative impact on the outcome either: (1) indirectly through the negative emotional responses that it produces, which can cause biological or behavioural changes; or (2) directly through the biological or behavioural changes, which can in turn negatively affect the emotional response. CONCLUSIONS: The proposed biopsychosocial model assumes that LBP-related chronic disability is possibly, in some cases, a stress related disorder. Its empirical verification in LBP could particularly improve the understanding of the interrelationships between certain variables. PMID- 11762879 TI - Factors associated with carer strain in carers of people with multiple sclerosis. AB - PURPOSE: To examine the factors associated with strain in carers of people with multiple sclerosis (MS). METHOD: People with MS were recruited from an MS management clinic. Demographic information, memory, executive function, attention/concentration, mood, disability and health of the person with MS, the carer's opinion of the care-recipient's memory and disability, and the carer's mood were recorded. A postal questionnaire to identify factors associated with carer strain was sent to carers. A further questionnaire was sent to carers to examine the association between memory problems in people with MS and carer strain. RESULTS: Problems with everyday memory and activities of daily living were found to be associated with carer strain. Strained carers perceived strain to be a consequence of the memory problems (p < 0.01). Aspects of the memory problems related to carer strain were the amount of time a carer could spend alone (p = 0.01), the carer's mood and less sympathetic feelings towards the person with MS (p < 0.05). Strained carers had more desire for other people to help the person with MS deal with the memory problems by themselves than carers who were not under strain (p = 0.03). CONCLUSION: Carer strain was associated with memory problems experienced by people with MS. PMID- 11762880 TI - Factors associated with home environmental problems among community-living older people. AB - PURPOSE: This paper describes the types of difficulties older people have with their home environments and the factors associated with having such difficulties. METHOD: Data were used from 296 study participants of the University at Buffalo's Consumer Assessments Study that examines the home modification needs and environmental difficulties of older people. A combination of socio-demographic variables, health and functional status indicators and measures of psychosocial well-being were used to predict environmental problems. RESULTS: An average of 13 problems with the environment that posed as a barrier to safe and independent performance was observed in homes. It was found that most difficulties occurred in bathrooms, kitchens, bedrooms and access to entryways and rooms. Hierarchical multiple regression analysis showed that having home environmental problems was most strongly associated with younger age, being female, being of minority status, having pain, and greater physical disability. CONCLUSION: The findings show that a combination of conditions that include demographic and functional conditions place older people at risk for problems with the home environment that impede performance of daily living activities. PMID- 11762881 TI - The illness experience of adult persons with muscular dystrophy. AB - PURPOSE: The purpose of the present study is to describe the illness experience of persons with muscular dystrophy, their experience of activities of daily living, and whether there are any differences in how different types of muscular dystrophy affect people's lives. METHOD: Fifty-eight subjects were interviewed on two occasions. The interviews with 15 subjects (five for each type of muscular dystrophy; proximal muscular dystrophy, myotonic muscular dystrophy, myopathia distalis tarda hereditaria) were subjected to inductive content analysis. The interviews were about experiences of the first symptoms, learning of the diagnosis, life in general from then to the present, managing daily living and thoughts about the future. RESULTS: After a deductive validation procedure the results were presented as three core narratives', one for each type of muscular dystrophy. The illness experience was mainly similar irrespective of type of muscular dystrophy. Learning of the incurable, progressive, hereditary disease was traumatic and the subjects hoped the diagnosis was wrong. They felt uncertain about the future, and were sad and worried about the consequences of a hereditary disease for their children. CONCLUSION: The results will enable rehabilitation staff to better understand the patient's need for psychosocial support. PMID- 11762882 TI - The prevalence and characteristics of physical and sensory disabilities in Northern Ethiopia. AB - PURPOSE: To identify disabilities and to determine their prevalence, age of onset and perceived cause in one urban and three rural areas in Northern Ethiopia. METHOD: A community based cross-sectional study of households that were selected by systematic sampling. Trained enumerators identified individuals with physical disabilities or epilepsy who were 5 years of age or older. RESULTS: The overall prevalence of disability in 4214 individuals was 4.9%. The more common forms were walking difficulty (1.7%), loss of vision in one or both eyes (1.5%), hand dysfunction (0.8%) and epilepsy (0.7%). Information provided by the interviewees revealed a pattern of early onset, with injury and infection prominent as perceived causes. The importance of injury and infections was confirmed by the findings in half the people with disability, who were examined by a surgeon. CONCLUSIONS: Disability is a major public health problem and more facilities for rehabilitation and social support are needed. Measures that are needed to reduce the prevalence include health promotion, preventing injury, widening immunization coverage, better childhood nutrition and effective treatment for infection and injury. Further research should include younger children, cover a wider range of disability and use more sensitive means to detect hearing loss. PMID- 11762883 TI - What do we know about life on acute psychiatric wards in the UK? A review of the research evidence. AB - Despite the development of community care and associated processes of de institutionalisation, the hospital remains the hub of mental health services in the UK. However, previous quantitative and survey research indicates that quality of care in acute psychiatric (admission) wards has been compromised or is under threat, and points to a bleak experience for people who are admitted. Indicators of this include that there have been increases in admission rates, the proportion of compulsory admissions, and bed occupancy rates. There is also evidence of violence, sexual harassment and substance misuse in this setting, accompanied by rapid staff turnover, low staff morale, and an increasing proportion of 'difficult' patients (especially young men with schizophrenia). This paper reviews the evidence about life on psychiatric wards, focusing on how it is experienced by patients in acute settings. Research conducted in the UK in the 1990s, supports the impression that organisational pressures are having a negative impact on the quality of care. It shows that: nurse-patient (N-P) relationships are perceived to be an important aspect of care, but that N-P contact has declined; and patients are critical of conditions on the ward and view life there as both boring and unsafe. However, very little in-depth ethnographic research has been conducted on acute wards in the UK (and none since the 1970s) leaving us with a 'black box' view of in-patient care in this setting. Studies conducted during earlier 'care paradigms', notably those in the USA by Goffman and Strauss et al., provide useful insights into the patient's experience, but the extent to which these can be conceptually generalised to the present situation is unknown. The paper concludes by outlining questions and priorities for future investigation, focusing on the role of qualitative research. PMID- 11762884 TI - Using an interactive framework of society and lifecourse to explain self-rated health in early adulthood. AB - This paper presents an integrated model of the determinants of adult health combining lifecourse factors and contemporary circumstances. Using the 1958 British Birth Cohort, it operationalises lifecourse influences in terms of factors from birth to age 33, which might act through latent, pathway, or cumulative effects. Contemporary circumstances are represented by variables at different levels of social aggregation: macro (socio-economic circumstances); meso (involvement in civil society functions); micro (personal social support); and intersecting (job insecurity and life control). Multiple regression models were fitted, using self-rated health at age 33 as the health outcome. To allow for temporal ordering of events, early life factors were entered first in the final model, followed by later childhood factors and, finally current factors. Self-rated health was predicted by variables representing both early and later stage of the lifecourse and also contemporary societal-level factors. The effects of childhood factors were not removed by including contemporary factors, and conversely, contemporary factors contributed to the prediction of self-rated health over and above lifecourse factors. The factors were not collinear; supporting the notion that each dimension was distinct from the others. Although the model accounted for only 9% of the variance in self-rated health, the general conclusion is that both lifecourse and contemporary circumstances should be considered together in explaining adult health. PMID- 11762885 TI - An investigation into the cyclical incidence of dengue fever. AB - The purpose of this research was to review the topic of dengue fever transmission and investigate the relationship between seasonal temperature fluctuations and cyclical dengue fever incidence. Data from Puerto Rico (1988-1992) were used to test the model proposed. Dengue fever is a viral disease caused by any one of four antigenically distinct serotypes. It is transmitted by Aedes mosquitoes and infects 80 million people per year. Currently, dengue is endemic in specific tropical and subtropical regions worldwide and epidemic dengue has been reported in the Americas, Asia and some Pacific Islands. Data for Puerto Rico were collected from the NCDC/NOAA and a study conducted by Perez et al. (1994). Multivariate linear regression analysis was used to determine if a relationship exists between the monthly mean temperature lagged and the monthly incidence of dengue fever in Puerto Rico. Statistical significance was achieved and a second order model produced an R2 of 0.71. A residual analysis reveals positive autocorrelation, thus weakening the model's power to predict monthly dengue incidence. This suggests that other forces or factors related to the history of the herd immunity, the introduction of a new serotype, or demographic transitions are also influencing the cyclical transmission of dengue fever. Case clustering information, regional dengue distributions, and population density transformations must also be obtained in order to assess the forecasting ability of this model. Additional research is needed to avoid oversimplifying the problem. Without such attempts at establishing significant correlations, dengue prevention and control will remain a formidable task for many developing and developed countries. PMID- 11762886 TI - Accessibility and spatial distribution of general practice services in an Australian city by levels of social disadvantage. AB - The accessibility and spatial distribution of health services provided by the main source of primary medical care in Australia--the general practice surgery- was investigated by level of social disadvantage of local catchment areas. All 459 general practice surgeries in Perth, an Australian city of 1.2 million residents, were surveyed with a 94% response. Amount of service provision was measured using weekly doctor-hours, available from consulting rooms during opening hours, and associated nurse-hours of service. Access factors were defined as the distance to the nearest surgery, provision of Sunday and evening services, ease of making a same day appointment, bulk-billing, and whether the surgery offered a choice of gender of doctor. There were relatively more surgeries in disadvantaged areas and doctor-hours of service provision were also greater (41.0 h/1,000 most disadvantaged vs. 37.9 h/1000 least disadvantaged). Bulk-billing care, at no direct cost to the patient, was more likely to be provided in most disadvantaged areas compared with least disadvantaged areas (61 vs. 38%). However, populations living in the most disadvantaged areas were less likely to be able to see the local GP at short notice (91 vs. 95%), to have access to a local female GP (56 vs. 62%) or a local service in the evenings (42 vs. 51%). While the overall picture of accessibility was favourable, there was considerable variation in the type of services provided to different socioeconomic groups. Health care planners should investigate the reasons for these differences and advise Government to ensure that access factors affecting publicly funded services are equitably distributed. PMID- 11762887 TI - What determines health? To where should we shift resources? Attitudes towards the determinants of health among multiple stakeholder groups in Prince Edward Island, Canada. AB - The population health perspective has become significant in academic and policy discourse. The purpose of this paper is to assess its significance among health care practitioners and administrators as well as the general public. Respondents in Prince Edward Island, Canada were asked to rank the broad determinants of health and comment on to where resources should be shifted to improve the health of the population. Important variations are noted between the groups with family physicians and front-line staff being similar in perceptions to the general public on most determinants than other groups. The paper concludes with discussion on the relevance of the findings for population health research and health policy. PMID- 11762888 TI - Health behaviour, risk awareness and emotional well-being in students from Eastern Europe and Western Europe. AB - Life expectancy and other indices of health have deteriorated markedly in the former socialist countries of Eastern Europe over recent decades. The possible roles of lifestyles, knowledge about health and behaviour, emotional wellbeing and perceptions of control were assessed in a cross-sectional survey of young adults of similar educational status in Eastern and Western Europe. As part of the European Health and Behaviour Survey, data were collected in 1989-1991 from 4170 university students aged 18-30 years from Austria, Belgium, the Federal Republic of Germany, the Netherlands and Switzerland, and from 2293 students from the German Democratic Republic, Hungary and Poland. Measures were obtained of health behaviours, awareness of the role of lifestyle factors in health, depression, social support, health locus of control, and the value placed on health. After adjustment for age and sex, East European students had less healthy lifestyles than Western Europeans according to a composite index of 11 health behaviours, with significant differences for seven activities: regular exercise, drinking alcohol, avoiding dietary fat, eating fibre, adding salt to food, wearing a seat-belt, and using sunscreen protection. East European students were less likely to be aware of the relationship between lifestyle factors (smoking, exercise, fat and salt consumption) and cardiovascular disease risk. In addition, they were more depressed (adjusted odds of elevated scores on the Beck Depression Inventory of 2.46, 95% C.I. 1.95-3.09), reported lower social support, and had higher beliefs in the "chance" and "powerful others" locus of control. Internal locus of control levels did not differ across regions, and Eastern Europeans placed a higher valuation on their health. Unhealthy lifestyles associated with lack of information about health and behaviour, greater beliefs in uncontrollable influences, and diminished emotional well-being, may contribute to poor health status in Eastern Europe. PMID- 11762889 TI - Cataract surgery in a community hospital outreach clinic: patients' costs and satisfaction. AB - A cataract day surgery service for the population of central Norfolk, UK, was provided by the main ophthalmic department in a district general hospital and in an outreach clinic in a community hospital 40 km distant. The outreach clinic aimed to extend the accessibility of this particular service in a rural area where many patients faced long journeys to the main hospital. Samples of 201 patients attending the main hospital for day cataract surgery and 198 patients attending the outreach clinic for the same procedure were identified. Patients were interviewed and given questionnaire forms to establish their general health before the operation, their arrangements to get to hospital and their satisfaction with the clinic and the care they had received. The sample of patients attending the outreach clinic was slightly older, less affluent and in slightly poorer general health than the patients attending the main hospital. The two samples were similar in terms of visual acuity after the operation, complication rates, satisfaction with the outcome of the operation and subsequent use of health services. The journey to hospital was quicker, more convenient and less costly for the outreach clinic patients than the main hospital patients. The net benefit to patients of the outreach clinic was estimated as pounds sterling 39,000 per annum. Satisfaction with administrative matters, facilities at the two clinics and the care received was high in both samples, but patients were significantly more satisfied with arrangements at the smaller outreach clinic. This evidence suggests that an outreach clinic in a small community hospital can provide cataract day surgery under local anaesthesia as effectively as a district centre, at a reduced social cost and with positive social benefits. Further study of heath service costs is vital, but political pressure to acknowledge patient preferences for more local services is growing. PMID- 11762890 TI - Determinants of general practitioner use among women in Australia. AB - This study investigates the use of general practitioner services by women in Australia. Although there is a universal health insurance system (Medicare) in Australia, there are variations in access to services and out of pocket costs for services. Survey data from 2350 mid-age (45-50 years) and 2102 older (70-75 years) women participating in the Australian Longitudinal Study on Women's Health were linked with Medicare data to provide a range of individual and contextual variables hypothesised to explain general practitioner use. Structural equation modelling showed that physical health was the most powerful explanatory factor of general practitioner use. However, after adjusting for self-reported health, out of pocket cost per consultation was inversely associated with use of services. The out of pocket cost was generally lower for women with low socioeconomic status but cost was also directly related to geographical remoteness. Women living in more remote areas had higher out of pocket costs and poorer access to services. Women who reported better access to care were more likely to be satisfied with their most recent general practice consultation and less likely to be sceptical of the value of medical care. These results show the need for health policies that improve the equitable use of general practitioner services in Australia. PMID- 11762891 TI - Family effects on self-reported health among Russian wives and husbands. AB - Alcohol abuse and a transition to the market economy are often blamed for high mortality and low life expectancy in Russia, but little is known about proximate influences on individual health. This study estimates family influences on the self-reported health of Russian wives and husbands. Predicting gender differences in the determinants of health status, hypotheses are presented for the effects on spouses' self-reported health of five family characteristics: economic status, household division of labor, family decision-making, presence of young children, and housing conditions. Controls are included for age, education, sensitivity, alcohol use, job-related time, and urban-rural location. Data from a 1996 sample of couples (n = 925) from Moscow and two rural regions of Russia are analyzed using logistic regression. The findings provide mixed support for the hypotheses, though they do show the important role of family characteristics on spouses' health. Family economic standing is important to both spouses' self-reported health, though young children in the home is not. Family decision-making does influence spouses' health: when Russian wives are the primary decision makers in the family, their own health suffers, though their husbands' health is better. And support is found for the combined effects of job-related time and household labor but only for wives' health. When wife's household labor is low, the probability of her having poor health increases, the more time she devotes to her job. However, when she does substantially more domestic labor than her husband, her job-related time has the opposite effect, reducing the chances of poor health, the more time she spends on job activities. This study is important both in helping to account for poor health of Russians during the current economic and social transition and in identifying aspects of family life that affect men's and women's health cross-nationally. PMID- 11762892 TI - The main determinants of infant mortality in Nepal. AB - Infant mortality has reached a low stable rate in developed countries while it is still high and on a slow decline in developing countries. There are many factors that contribute to the incidence of a high or low level of infant mortality. Although credit for contributing to the lowering of infant mortality has been given to health programs by public health personnel and to the improvement in socio-economic status by social scientists, in a traditional and agricultural country such as Nepal, both these factors are found to influence infant mortality. Data on infant mortality obtained by the 1991 Demographic Health Survey of Nepal are analyzed in this study. A logistic regression model is used for analyzing the data. Several hypotheses are tested to explain the incidence of infant mortality in Nepal. The various reasons for the persistence of high infant mortality and the difficulties in lowering it are discussed. The findings suggest that among all the variables analyzed in the study, parity, place of residence, immunization, and ethnicity influence infant mortality the most. PMID- 11762893 TI - Risk factors and child mortality among the Miao in Yunnan, Southwest China. AB - Environmental factors and the lifestyle of communities in developing countries as in the industrialized world have a great deal to do with their health status. This study carried out among the Miao people of southeastern Yunnan province in Southwest China has demonstrated important links between child mortality (one indicator of health status) and specific risk factors. These include lifestyle variables such as geographic mobility, the age of weaning and religious belief. In addition, the use of available health care facilities was another explanatory variable. Perhaps surprisingly, a history of tuberculosis seemed also to be empirically related to the presence or absence of child mortality. Although it was impossible to show a significant statistical relationship between traditional practices and child mortality from the study's database, the authors have observed qualitatively that birthing customs play an important role in explaining the perinatal component of child mortality. These various relationships shed some light on potential areas for intervention with a view to reducing the levels of child mortality among minority peoples in China and elsewhere. PMID- 11762894 TI - When the bough breaks: provider-initiated comprehensive care is more effective and less expensive for sole-support parents on social assistance. AB - This 5-year study conducted in Ontario, Canada is designed to assess the effects and expense of adding a mix of provider-initiated interventions to the health and social services typically used in a self-directed manner by sole-support parents and their children receiving social assistance in a national system of health and social insurance. Results from a 2-year interim analysis show that providing social assistance families with proactive comprehensive care (health promotion, employment retraining, and recreation activities for children) compared to allowing families to fend for themselves in a self-directed manner, results in 15% more exits from social assistance within 1 year and substantial savings to society in terms of social assistance payouts. It is no more expensive to provide health and social services in a comprehensive fashion, and equivalent reductions in parent mood disorder and child behavior disorders, as well as equivalent increases in parent social adjustment and child competence levels were also observed. This study presents clear evidence that providing comprehensive care to social assistance recipients produces tremendous short- and long-term financial gains and societal benefits. PMID- 11762895 TI - Deprivation and mortality: the implications of spatial autocorrelation for health resources allocation. AB - This paper aims at investigating whether the relationship between mortality and socio-economic deprivation is affected by the spatial autocorrelation of ecological data. A simple model is used in which mortality (all-ages and premature) is the dependent variable, and deprivation, morbidity and other socio economic indicators are the explanatory variables. Deprivation is measured by the Townsend index; the other socio-economic variables are the median income, unequal income distribution (Gini coefficient) and population density. Morbidity is estimated on the basis of hospital admission rates and overweight prevalence. Spatial autocorrelation is measured by the Moran's I coefficient. All mortality and morbidity variables have significant, positive, and moderate-to-high spatial autocorrelation. Two multivariate models are explored: a weighted least-squares model ignoring spatial autocorrelation and a simultaneous autoregressive model. The paper concludes that spatial autocorrelation has a significant impact on the relationship between mortality and socio-economic variables. Future ecological models intended to inform health resources allocation need to pay greater attention to the spatial dimension of the data used. PMID- 11762896 TI - Medical audit: threat or opportunity for the medical profession. A comparative study of medical audit among medical specialists in general hospitals in The Netherlands and England, 1970-1999. AB - Medical audit has been introduced among hospital specialists in both the Netherlands and England. In the Netherlands following some local experiments, medical audit was promoted nationally as early as 1976 by the medical profession itself and became a mandatory activity under the Hospital Licensing Act of 1984. In England it was the government who promoted medical audit as a compulsory activity for medical specialists, in particular since 1989. In this article the development and introduction of medical audit in the two health care systems is described and its impact on the clinical autonomy of medical specialists gauged. It is concluded that in both countries external pressures seem to have been crucial in the 'compulsory' introduction of medical audit. Although there are differences in the organisation and culture of the medical profession in the two countries, in both countries medical audit turned out to be an instrument 'controlled' by the profession itself. The question whether medical audit is instrumental in preserving clinical autonomy has also been addressed. Our conclusion is that in its present form medical audit in the two countries has not been a threat to the clinical autonomy of the medical profession. At the same time it is clear that the study of one quality instrument is insufficient to draw conclusions about the development of clinical autonomy, let alone autonomy in general. Moreover, it remains to be seen how medical audit can survive alongside quality improvement mechanisms such as accreditation, certification, performance indicators and formal quality systems (ISO, EFQM) where hospital management executes more control. The history of medical audit in the Netherlands and England over the past 30 years does illustrate, however, the capability of the profession to maintain autonomy through re-negotiated mechanisms for self control. PMID- 11762897 TI - Effect of lateral connections on the accuracy of the population code for a network of spiking neurons. AB - We study how neuronal connections in a population of spiking neurons affect the accuracy of stimulus estimation. Neurons in our model code for a one-dimensional orientation variable phi. Connectivity between two neurons depends on the absolute difference absolute value(phi - phi') between the preferred orientation of the two neurons. We derive an analytical expression of the activity profile for a population of neurons described by the spike response model with noisy threshold. We estimate the stimulus orientation and the trial-to-trial fluctuations using the population vector method. For stationary stimuli, uniform inhibitory connections produce a more reliable estimation of the stimulus than short-range excitatory connections with long-range inhibitions, although the latter interaction type produces a sharper tuning curve. These results are consistent with previous analytical studies of the Fisher information. PMID- 11762898 TI - Speed of feedforward and recurrent processing in multilayer networks of integrate and-fire neurons. AB - The speed of processing in the visual cortical areas can be fast, with for example the latency of neuronal responses increasing by only approximately 10 ms per area in the ventral visual system sequence V1 to V2 to V4 to inferior temporal visual cortex. This has led to the suggestion that rapid visual processing can only be based on the feedforward connections between cortical areas. To test this idea, we investigated the dynamics of information retrieval in multiple layer networks using a four-stage feedforward network modelled with continuous dynamics with integrate-and-fire neurons, and associative synaptic connections between stages with a synaptic time constant of 10 ms. Through the implementation of continuous dynamics, we found latency differences in information retrieval of only 5 ms per layer when local excitation was absent and processing was purely feedforward. However, information latency differences increased significantly when non-associative local excitation was included. We also found that local recurrent excitation through associatively modified synapses can contribute significantly to processing in as little as 15 ms per layer, including the feedforward and local feedback processing. Moreover, and in contrast to purely feed-forward processing, the contribution of local recurrent feedback was useful and approximately this rapid even when retrieval was made difficult by noise. These findings suggest that cortical information processing can benefit from recurrent circuits when the allowed processing time per cortical area is at least 15 ms long. PMID- 11762899 TI - Neural coding and decoding: communication channels and quantization. AB - We present a novel analytical approach for studying neural encoding. As a first step we model a neural sensory system as a communication channel. Using the method of typical sequence in this context, we show that a coding scheme is an almost bijective relation between equivalence classes of stimulus/response pairs. The analysis allows a quantitative determination of the type of information encoded in neural activity patterns and, at the same time, identification of the code with which that information is represented. Due to the high dimensionality of the sets involved, such a relation is extremely difficult to quantify. To circumvent this problem, and to use whatever limited data set is available most efficiently, we use another technique from information theory--quantization. We quantize the neural responses to a reproduction set of small finite size. Among many possible quantizations, we choose one which preserves as much of the informativeness of the original stimulus/response relation as possible, through the use of an information-based distortion function. This method allows us to study coarse but highly informative approximations of a coding scheme model, and then to refine them automatically when more data become available. PMID- 11762900 TI - Pattern recognition in a compartmental model of a CA1 pyramidal neuron. AB - Computer simulation of a CA1 hippocampal pyramidal neuron is used to estimate the effects of synaptic and spatio-temporal noise on such a cell's ability to accurately calculate the weighted sum of its inputs, presented in the form of transient patterns of activity. Comparison is made between the pattern recognition capability of the cell in the presence of this noise and that of a noise-free computing unit in an artificial neural network model of a heteroassociative memory. Spatio-temporal noise due to the spatial distribution of synaptic input and quantal variance at each synapse degrade the accuracy of signal integration and consequently reduce pattern recognition performance in the cell. It is shown here that a certain degree of asynchrony in action potential arrival at different synapses, however, can improve signal integration. Signal amplification by voltage-dependent conductances in the dendrites, provided by synaptic NMDA receptors, and sodium and calcium ion channels, also improves integration and pattern recognition. While the biological sources of noise are significant when few patterns are stored in the associative memory of which the cell is a part, when large numbers of patterns are stored the noise from the other stored patterns comes to dominate the pattern recognition process. In this situation, the pattern recognition performance of the pyramidal cell is within a factor of two of that of the computing unit in the artificial neural network model. PMID- 11762901 TI - A hybrid learning network for shift, orientation, and scaling invariant pattern recognition. AB - A three-layer neural network is presented as a generic approach for visual pattern recognition invariant with respect to the geometric appearance such as translation, orientation and scale of the patterns. The invariant recognition is achieved by representing the geometric variations internally in the network by nodes in the input and middle layers, which are laterally connected and trained by a hybrid algorithm combining both competitive and Hebbian learning. As the result of the hybrid learning, each pattern will be represented by a particular subset of middle-layer nodes all specialized to respond to the same pattern but with different geometric appearances. The nodes in the output layer are then trained by competitive learning to recognize the different pattern internally represented by the middle-layer nodes, independent of their location, orientation and size. The proposed algorithm is generic and robust and can be applied to various practical recognition problems. Moreover, the network is relatively simple and biologically plausible and can serve as a computational model to account for the invariant object recognition in the biological visual system. PMID- 11762902 TI - The influence of earthworm-processed pig manure on the growth and productivity of marigolds. AB - The effects of additions of earthworm-processed pig manure (vermicompost) on the growth and productivity of French marigold (Tagetes patula) plants were evaluated under glasshouse conditions. Marigolds were germinated and grown in a standard commercial greenhouse container medium (Metro-Mix 360), substituted with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% (by volume) pig manure vermicompost. The control consisted of Metro-Mix 360 alone without vermicompost. Plants were supplied regularly with a complete mineral nutrient solution for 121 days. The greatest vegetative growth resulted from substitution of Metro-Mix 360 with 30% and 40% pig manure vermicompost, and the lowest growth was in the potting mixtures containing 90% and 100% vermicompost. Most flower buds occurred in the potting mixtures containing 40% pig manure vermicompost (19.4 buds), and fewest in the potting mixtures containing 100% vermicompost. Marigolds grown in Metro-Mix 360 substituted with 90% and 100% pig manure vermicompost had the fewest and smallest flowers. After substitution of Metro-Mix 360 with 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% vermicompost, the marigold roots were larger than those of plants grown in the Metro-Mix 360 controls. Substitution of Metro Mix 360 with any concentration of pig manure vermicompost, with all needed nutrients provided, increased the overall nitrate-nitrogen concentrations of the marigold leaf tissues at flowering stage. Some of the marigold growth and productivity enhancement, resulting from substitution of Metro-Mix 360 with pig manure vermicompost, may be explained by nutritional factors; However, other, factors, such as plant-growth regulators and humates, might have also been involved since all plants were supplied regularly with all required nutrients. PMID- 11762903 TI - Simulation of a cross-flow shrinking-bed reactor for the hydrolysis of lignocellulosics. AB - An idealized model is developed for the case in which biomass slurry is conveyed through an annulus, with water or steam entering through an inner porous wall and liquid product leaving through an outer porous wall. It is assumed that the ratio of occluded liquid to solid in the slurry is a constant, Rws, and that non occluded water is immediately removed from the reactor. The goal of > 90% sugar yield with > 10% sugar in the product is almost reached (88% glucose yield, 91% xylose yield, 47 g/l glucose and 45 g/l xylose) at 240 degrees C, 1% acid. Rws = 1 and a radial wash water flow of three times the initial mass flow of solids to the reactor per meter of reactor length per g/l of sugar concentration in the occluded water. If Rws is limited to 3, the yield falls to 85% and the total sugar concentration to 61 g/l. Even without cross-flow wash, the yields can be increased by about 16 percentage points, compared to plug flow, by extracting excess liquid through the outer wall as it is formed. At 200 degrees C, where one might prefer to operate for ease of control and concern about the possibility of making fermentation inhibitors at higher temperatures, the maximum glucose yield in a plug-flow reactor is low (12-13%) whereas in a cross-flow reactor, at a high cross-flow wash rate, it can still be quite high (60-83%) but at a very low concentration (0.57-1.47%). In these simulations it is assumed that one-half of the inerts is solubilized. The formation of oligomers is neglected. PMID- 11762904 TI - The effect of aeration on the biotransformation of lignocellulosic wastes by white-rot fungi. AB - The mineralisation and the humification of organic matter (OM) in sterile horticultural plant wastes inoculated with Coriolus versicolor or Phanerochaete flavido-alba was investigated under different aeration rates in order to determine their efficacy as potential inoculants for composting. The change in elemental composition, lignin content and OM fractions was analysed during a 90 day incubation. Both fungi degraded 30% of lignin at low aeration rates. Different aeration rates led to significant changes in OM mineralisation induced by C. versicolor, but did not have noticeable effect on P. flavido-alba activity. The mineralisation was more effectively carried out by P. flavido-alba than by C. versicolor. Lignin degradation and the linked humification process were equally achieved by the two fungi and were enhanced in aerated conditions. The fungi analysed may facilitate the composting of lignocellulosic wastes by means of an increase in substrate bioavailability and OM humification. PMID- 11762905 TI - Optimization of urease immobilization onto non-porous HEMA incorporated poly(EGDMA) microbeads and estimation of kinetic parameters. AB - Jack bean urease (urea aminohydrolase, EC 3.5.1.5) was immobilized onto modified non-porous poly(ethylene glycol dimethacrylate/2-hydroxy ethylene methacrylate), (poly(EGDMA/HEMA)), microbeads prepared by suspension copolymerization for the potential use in hemoperfusion columns, not previously reported. The conditions of immobilization; enzyme concentration, medium pH, substrate and ethylene diamine tetra acetic acid (EDTA) presence in the immobilization medium in different concentrations, enzyme loading ratio, processing time and immobilization temperature were investigated for highest apparent activity. Immobilized enzyme retained 73% of its original activity for 75 days of repeated use with a deactivation constant kd = 3.72 x 10(-3) day(-1). A canned non-linear regression program was used to estimate the intrinsic kinetic parameters of immobilized enzyme with a low value of observable Thiele modulus (phi < 0.3) and these parameters were compared with those of free urease. The best-fit kinetic parameters of a Michaelis-Menten model were estimated as Vm = 3.318 x 10(-4) micromol/s mg bound enzyme protein, Km = 15.94 mM for immobilized, and Vm = 1.074 micromol NH3/s mg enzyme protein, Km = 14.49 mM for free urease. The drastic decrease in Vm value was attributed to steric effects, conformational changes in enzyme structure or denaturation of the enzyme during immobilization. Nevertheless, the change in Km value was insignificant for the unchanged affinity of the substrate with immobilization. For higher immobilized urease activity, smaller particle size and concentrated urease with higher specific activity could be used in the immobilization process. PMID- 11762906 TI - Preliminary studies on TCF bleaching of Pinus pinaster acetosolv pulps. AB - Oxygen pre-treatment of Pinus pinaster acetosolv pulps has been studied as a first step towards TCF bleaching. Using a 2(3) factorial design, the influence of temperature (80-120 degrees C), time (1-2 h) and NaOH concentration (1.5-3%) on pulp yield in the oxygen stage, chemical composition and physical properties of the pulps obtained was studied. Pulps pre-bleached with oxygen in the conditions selected as optimal (80 degrees C, 1 h with 2.25% NaOH) have been bleached with TCF sequences which included stages with hydrogen peroxide or hydrogen peroxide oxygen under pressure. Even if high degrees of delignification were reached, with a reduction in Kappa number up to 95% and without important loss of viscosity, the carbohydrates degradation, especially hemicelluloses in the acetic acid delignification, reduces the strength potential of the pulps. PMID- 11762907 TI - Petiolar felt-sheath of palm: a new biosorbent for the removal of heavy metals from contaminated water. AB - Biosorption of heavy metals such as Pb2+, Ni2+, Cd2+, Cu2+, Cr3+ and Zn2+ by petiolar felt-sheath of palm (PFP) from contaminated water was examined. PFP was found to efficiently remove all the toxic metal ions with selectivity order of Pb2+ > Cd2+ > Cu2+ > Zn2+ > Ni2+ > Cr3+. The uptake was rapid, with more than 70% completed within 15 min. The bound metal ions were successfully desorbed and the PFP fibrous-biomass remained effective after several adsorption-desorption cycles. PMID- 11762908 TI - Decolourisation of the textile dye Astrazon Red FBL by Funalia trogii pellets. AB - The effects of various conditions such as initial pH, dye concentrations, amount of pellet, temperature and agitation on decolourising activity of Funalia trogii were investigated. These, except initial pH, were all found to be important for dye decolourising activity of F. trogii. The decolourisation of the dye involved adsorption of the dye compound by fungal pellets at the initial stage, followed by the decolourisation through microbial metabolism. Heat-killed pellets were also tested for their ability to decolourise Astrazon Red dye. These pellets adsorbed the dye and 55% decolourisation was obtained in 24 h. But at the second cycle there was only 24% decolourisation. Our observation showed that Astrazon Red dye decolourisation by heat-killed pellets was mainly due to biosorption. The longevity of the decolourisation activity of F. trogii pellets was also investigated in repeated batch mode. Variations in the amount of pellet increased % decolourisation and stability of pellets. PMID- 11762909 TI - Utilization of waste materials for outdoor wintering of Apis mellifera L. colonies. AB - The studies were conducted for two years during 1996-1997 and 1997-1998 to evaluate the impact of different waste materials wheat bhusa (chopped wheat straw), paddy straw, sawdust and thermocole sheet (a type of polystyrene board) as inner packing, and in combination with polythene sheets as outer packing, on the brood rearing activity of honeybee (Apis mellifera L.) colonies. The increase in brood area showed that thermocole alone as well as in combination with polythene sheets was superior to all other treatments; followed by paddy straw, wheat bhusa and saw dust, respectively. Considering the economic feasibility and easy availability, the paddy straw packing is recommended for outdoor wintering of honeybee colonies. PMID- 11762910 TI - Bioconversion of eucalyptus bark waste into soil conditioner. AB - An optimized protocol for the bioconversion of eucalyptus bark was devised. It comprised: (i) mechanical reduction in bark size to 0.5-3.0 cm, (ii) moistening to 60-65%, (iii) fortification with ligninase-rich fungus Volvariella sp. (S-1) and 2% urea and (iv) maintenance of this composting mix under aerobic and ambient condition for 14-15 weeks. The resulting bark soil conditioner (BSC) was an easily crumbling, reddish brown biomass, with physico-chemical and microbial properties which would enrich soil fertility/productivity. PMID- 11762911 TI - Plant growth-promoting oligosaccharides produced from tomato waste. AB - Tomato juice waste was hydrolyzed with acid. Tomato juice waste (500 g; wet weight) was heated with 0.5 N HCl (2.5 l) at 70 degrees C for 4 h. After neutralization, the growth-promoting extracts (300 g; dry weight) in the plants were produced from the tomato waste. The acid extract significantly promoted the growth of cockscomb (Celosia argentea L.) and tomato (Lycopersicon esculentum L.) seedlings. We have recognized potent plant growth-promoting substances in the acid extract from tomato waste. The most effective components in the active fraction were almost all oligogalacturonic acids (DP 6-12). This paper is the first report that plant growth-promoting oligosaccharides can be directly produced from tomato juice waste. It is possible that the substances from the tomato waste can become useful plant growth regulators in the agriculture field in the future. PMID- 11762912 TI - Role of conserved TGDGVND-loop in Mg2+ binding, phosphorylation, and energy transfer in Na,K-ATPase. AB - In the P-domain, the 369-DKTGTLT and the 709-GDGVNDSPALKK segment are highly conserved during evolution of P-type E1-E2-ATPase pumps irrespective of their cation specificities. The focus of this article is on evaluation of the role of the amino acid residues in the P domain of the alpha subunit of Na,K-ATPase for the E1P[3Na]--> E2P[2Na] conversion, the K+-activated dephosphorylation, and the transmission of these changes to and from the cation binding sites. Mutations of residues in the TGDGVND loop show that Asp710 is essential, and Asn713 is important, for Mg2+ binding and formation of the high-energy MgE1P[3Na] intermediate. In contrast Asp710 and Asp713 do not contribute to Mg2+ binding in the E2P-ouabain complex. Transition to E2P thus involves a shift of Mg2+ coordination away from Asp710 and Asn713 and the two residues become more important for K+-activated hydrolysis of the acyl phosphate bond at Asp369. Transmission of structural changes between the P-domain and cation sites in the membrane domain is evaluated in light of the protein structure, and the information from proteolytic or metal-catalyzed cleavage and mutagenesis studies. PMID- 11762913 TI - Conformational coupling: the moving parts of an ion pump. AB - The Na,K-ATPase carries out the coupled functions of ATP hydrolysis and cation transport. These functions are performed by two distinct regions of the protein. ATP binding and hydrolysis is mediated by the large central cytoplasmic loop of about 430 amino-acids. Transmembrane cation transport is accomplished via coordination of the Na and K ions by side-chains of the amino-acids of several of the transmembrane segments. The way in which these two protein domains interact lies at the heart of the molecular mechanism of active transport, or ion pumping. We summarize evidence obtained from protein chemistry studies of the purified renal Na,K-ATPase and from bacterially expressed polypeptides which characterize these separate functions and point to various movements which may occur as the protein transits through its reaction cycle. We then describe recent work using heterologous expression of renal Na,K-ATPase in baculovirus-infected insect cells which provides a suitable system to characterize such protein motions and which can be employed to test specific models arising from recently acquired high resolution structural information on related ion pumps. PMID- 11762914 TI - Structural organization and energy transduction mechanism of Na+,K+-ATPase studied with transition metal-catalyzed oxidative cleavage. AB - This chapter describes contributions of transition metal-catalyzed oxidative cleavage of Na+,K+-ATPase to our understanding of structure-function relations. In the presence of ascorbate/H2O2, specific cleavages are catalyzed by the bound metal and because more than one peptide bond close to the metal can be cleaved, this technique reveals proximity of the different cleavage positions within the native structure. Specific cleavages are catalyzed by Fe2+ bound at the cytoplasmic surface or by complexes of ATP-Fe2+, which directs the Fe2+ to the normal ATP-Mg2+ site. Fe2+- and ATP-Fe2+-catalyzed cleavages reveal large conformation-dependent changes in interactions between cytoplasmic domains, involving conserved cytoplasmic sequences, and a change of ligation of Mg2+ ions between E1P and E2P, which may be crucial in facilitating hydrolysis of E2P. The pattern of domain interactions in E1 and E2 conformations, and role of Mg2+ ions, may be common to all P-type pumps. Specific cleavages can also be catalyzed by Cu2+ ions, bound at the extracellular surfaces, or a hydrophobic Cu2+-diphenyl phenanthroline (DPP) complex, which directs the Cu2+ to the membrane-water interface. Cu2+ or Cu2+-DPP-catalyzed cleavages are providing information on alpha/beta subunit interactions and spatial organization of transmembrane segments. Transition metal-catalyzed cleavage could be widely used to investigate other P-type pumps and membrane proteins and, especially, ATP binding proteins. PMID- 11762915 TI - Electrogenic properties of the Na+,K+-ATPase probed by presteady state and relaxation studies. AB - Electrical measurements on planar lipid bilayers, patch/voltage clamp experiments, and spectroscopic investigations involving a potential sensitive dye are reviewed. These experiments were performed to analyze the kinetics of charge translocation of the Na+,K+-ATPase. High time resolution was achieved by applying caged ATP, voltage-jump, and stopped-flow techniques, respectively. Kinetic parameters and the electrogenicity of the relevant transitions in the Na+,K+ ATPase reaction cycle are discussed. PMID- 11762916 TI - Molecular and functional studies of the gamma subunit of the sodium pump. AB - This article reviews our studies of the gamma subunit of the sodium pump. Gamma is a member of the FXYD family of small, single transmembrane proteins and is expressed predominantly in the kidney tubule. There are two major variants of gamma which function similarly to bring about two distinct effects, one on K'(ATP) and the other, on K(K), the affinity of the pump for K+ acting as a competitor of cytoplasmic Na+. In this way, gamma is believed to provide a self regulatory mechanism for maintaining the steady-state activity of the pump in the kidney. Our studies also suggest that K+ antagonism of cytoplasmic Na+ activation of the pump is relevant not only to the presence of gamma in the kidney, but probably some hitherto undefined factor(s) in other tissues, most notably heart. The interesting possibility that not only gamma but other members of the FXYD family regulate ion transport in a tissue-specific manner is discussed. PMID- 11762917 TI - Modulation of Na,K-ATPase by associated small transmembrane regulatory proteins and by lipids. AB - The effects of phospholipid acyl chain length (n(c)) and cholesterol on Na,K ATPase reconstituted into liposomes of defined lipid composition are described. The optimal hydrophobic thickness of the lipid bilayer decreases from n(c) = 22 to 18 in the presence of 40 mol% cholesterol. Hydrophobic matching as well as specific interactions of cholesterol with the phosphorylation/dephosphorylation reactions is found to be important. A novel regulatory protein has been identified in Na,K-ATPase membrane preparations from the shark (phospholemmanlike protein from shark, PLMS) with significant homology to phospholemman (PLM), the major protein kinase substrate in myocardium. Both are members of the FXYD gene family. Another member of this family is the Na,K-ATPase gamma subunit indicating that these proteins may be specific regulators of the Na,K-ATPase. A regulatory mechanism is described in which association/dissociation of PLMS with the Na,K ATPase is governed by its phosphorylation by protein kinases. PMID- 11762919 TI - Short-term regulation of the proximal tubule Na+,K+-ATPase: increased/decreased Na+,K+-ATPase activity mediated by protein kinase C isoforms. AB - In different species and tissues, a great variety of hormones modulate Na+,K+ ATPase activity in a short-term fashion. Such regulation involves the activation of distinct intracellular signaling networks that are often hormone- and tissue specific. This minireview focuses on our own experimental observations obtained by studying the regulation of the rodent proximal tubule Na+,K+-ATPase. We discuss evidence that hormones responsible for regulating kidney proximal tubule sodium reabsorption may not affect the intrinsic catalytic activity of the Na+,K+ ATPase, but rather the number of active units within the plasma membrane due to shuttling Na+,K+-ATPase molecules between intracellular compartments and the plasma membrane. These processes are mediated by different isoforms of protein kinase C and depend largely on variations in intracellular sodium concentrations. PMID- 11762920 TI - CCL- and PLE-catalyzed reverse enantiomeric separation of various (+/-)-2 thienylcarbinols. AB - (+/-)-2-Thienylcarbinols and their O-acetyl derivatives were resolved in reverse separation by CCL and PLE catalysed hydrolysis to afford optically active 2 thienylcarbinols in 35%-99% e.e. that are valuable chiral building blocks, in particular in the synthesis of pheromones and some alkoloid type natural products. Absolute configurations were determined by the correlation of specific rotation values with the literature and by transforming into the corresponding secondary alcohols via reductive desulfurization by Ra-Ni. PMID- 11762918 TI - The functional role of beta subunits in oligomeric P-type ATPases. AB - Na,K-ATPase and gastric and nongastric H,K-ATPases are the only P-type ATPases of higher organisms that are oligomeric and are associated with a beta subunit, which is obligatory for expression and function of enzymes. Topogenesis studies suggest that beta subunits have a fundamental and unique role in K+-transporting P-type ATPases in that they facilitate the correct membrane integration and packing of the catalytic a subunit of these P-type ATPases, which is necessary for their resistance to cellular degradation, their acquisition of functional properties, and their routing to the cell surface. In addition to this chaperone function, beta subunits also participate in the determination of intrinsic transport properties of Na,K- and H,K-ATPases. Increasing experimental evidence suggests that beta assembly is a highly ordered, beta isoform-specific process, which is mediated by multiple interaction sites that contribute in a coordinate, multistep process to the structural and functional maturation of Na,K- and H,K ATPases. PMID- 11762921 TI - 2-Hydroxymethyl-1,4-dioxane: synthesis, resolution and determination of the absolute configurations of the enantiomers. AB - 2-Hydroxymethyl-1,4-dioxane 3 was resolved via salt formation between its hydrogen phthalate and (R)- or (S)-1-phenylethylamine, selective crystallization of the resultant diastereomeric mixtures and subsequent recovery of its enantiomers by saponification. The progress of the resolution was followed by chiral HPLC and the absolute stereochemistry of the two enantiomers determined by comparison of their specific rotations with that of (R)-3 synthesized from enantiomerically pure (R)-1-O-benzylglycerol. The results of the synthesis of 3 and of its resolution are discussed and compared with those previously obtained for 1,2-isopropylidene glycerol evaluating the consequences of replacement of ispropylidene with an ethylene bridge. PMID- 11762922 TI - Three-step synthesis of (R)- and (S)-thalidomides from ornithine. AB - Three-step synthesis of enantiomerically pure thalidomide is described. D Ornithine (2) reacted with thionyl chloride in methanol followed by treatment with triethylamine to give the (R)-3-amino-piperidin-2-one hydrochloride (3) in good yield. Protection of amino moiety by the use of N-carboethoxyphtalimide in DMSO furnished (R)-N-phtaloylpiperidin-2-one (4) as colorless crystals. Finally, the oxidation using a catalytic amount of RuO2 in the presence of excess sodium metaperiodate in a two-phase system gave (R)-thalidomide (1) in good yield without racemization. (S)-Thalidomide (1) was also synthesized from L-ornithine (2) in good overall yield. Since all the intermediates to thalidomide are easily recrystallized, the present method can be performed on a large scale without purification by column chromatography. PMID- 11762923 TI - Investigation of the enantioselectivity of three polypeptide liquid-crystalline solvents using NMR spectroscopy. AB - The enantioselective potentialities of three polypeptide liquid-crystalline solutions made of poly-gamma-benzyl-L-glutamate (PBLG), poly-gamma-ethyl-L glutamate (PELG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL) are investigated and compared using proton, carbon-13 and deuterium NMR spectroscopy. From a practical point of view, we propose an efficient alternative to the PBLG system, which is essential when this chiral homopolymer fails in distinguishing between enantiomers or enantiotopic elements. From a theoretical point of view, this study provides new information on the role of the lateral side chain of the polypeptide in the mechanisms of enantiodiscrimination. The various experimental results reported show the extraordinary adaptability of this methodology, and so enlighten the very large potential of NMR in chiral liquid crystals in the field of enantiomeric and enantiotopic analysis. PMID- 11762924 TI - The asymmetric Michael reaction involving chiral imines: recent progress at the Universite Paris-Sud. PMID- 11762925 TI - Mixed cobalt(III) complexes with aromatic amino acids and diamine. Part II. Synthesis and configuration of (1,2-diaminoethane)bis(L tyrosinato)cobalt(III)complex diastereomers. The crystal structure of the delta C1-cis(O) diastereomer. AB - In the reaction of trans-[CoCl2(en)2]+ with L-tyrosine all six theoretically possible diastereomers of the (1,2-diaminoethane)bis(L-tyrosinato)cobalt(III) complex were formed. The following five were isolated: gamma-trans(O); and gamma- and delta-C2-cis(O) and gamma- and delta-C1-cis(O) diastereomers, while the delta trans(O) diastereomer was only detected in the corresponding eluate. Separation of the obtained diastereomers was performed by chromatography on a Dowex 1 x 4 column. Characterization of the isolated diastereomers was carried out by means of elemental analysis, electronic absorption, circular dichroic, 1H and 13C NMR spectra, and by x-ray crystal structure analysis in the case of the delta-C1 cis(O) diastereomer. We established the general rule of preference of diasteromers formation in complexes of [Co(L-aa)2diamine]+ (L-aa = L-amino acid anion; diamine = 1,2-diaminoethane or 1,3-diaminopropane) type. PMID- 11762926 TI - Enantioresolution and absolute stereochemistry of a photochromic bis(benzo[b]thienyl)ethene compound. AB - The colored closed-ring isomers of a bis(benzo[b]thienyl) type photochromic diarylethene compound were enantioresolved by chiral column chromatography. The absolute stereochemistry of a (-)633-compound was determined by X-ray crystallography as (S,S). The relationship between the absolute stereostructure and the circular dichroism (CD) spectrum is discussed. PMID- 11762927 TI - Liquid chromatographic resolution of biphenyl dimethyl dicarboxylate (DDB) and its analogues on a chiral stationary phase. AB - Racemic biphenyl dimethyl dicarboxylate (DDB) and its analogues have been successfully resolved on a commercial HPLC chiral column, (3R,4S)-Whelk-O 1. In general, cyclic amide analogues of DDB, which were derived from pyrrolidine or piperidine, showed greater enantioselectivity and greater retention than the corresponding N,N-dialkyl amide or N-alkyl amide or ester analogues. From these results, it was concluded that the carbonyl oxygen of the DDB analogues plays an important role as a hydrogen bond acceptor, though the steric bulkiness of the amide functionality of DDB analogues may be another factor governing chiral recognition. The conformational stability of the two enantiomers of DDB and its analogues was also found to be high enough for the two enantiomers to be resolvable on (3R,4S)-Whelk-O 1. PMID- 11762928 TI - Determination of a site-specific reference dose for methylmercury for fish-eating populations. AB - Environmental risk-management decisions in the U.S. involving potential exposures to methylmercury currently use a reference dose (RfD) developed by the U.S. Environmental Protection Agency (USEPA). This RfD is based on retrospective studies of an acute poisoning incident in Iraq in which grain contaminated with a methylmercury fungicide was inadvertently used in the baking of bread. The exposures, which were relatively high but lasted only a few months, were associated with neurological effects in both adults (primarily paresthesia) and infants (late walking, late talking, etc.). It is generally believed that the developing fetus represents a particularly sensitive subpopulation for the neurological effects of methylmercury. The USEPA derived an RfD of 0.1 microg/kg/day based on benchmark dose (BMD) modeling of the combined neurological endpoints reported for children exposed in utero. This RfD included an uncertainty factor of 10 to consider human pharmacokinetic variability and database limitations (lack of data on multigeneration effects or possible long term sequelae of perinatal exposure). Alcoa signed an Administrative Order of Consent for the conduct of a remedial investigation/feasibility study (RI/FS) at their Point Comfort Operations and the adjacent Lavaca Bay in Texas to address the effects of historical discharges of mercury-containing wastewater. In cooperation with the Texas Natural Resource Conservation Commission and USEPA Region VI, Alcoa conducted a baseline risk assessment to assess potential risk to human health and the environment. As a part of this assessment. Alcoa pursued the development of a site-specific RfD for methylmercury to specifically address the potential human health effects associated with the ingestion of contaminated finfish and shellfish from Lavaca Bay. Application of the published USEPA RfD to this site is problematic; while the study underlying the RfD represented acute exposure to relatively high concentrations of methylmercury, the exposures of concern for the Point Comfort site are from the chronic consumption of relatively low concentrations of methylmercury in fish. Since the publication of the USEPA RfD, several analyses of chronic exposure to methylmercury in fish-eating populations have been reported. The purpose of the analysis reported here was to evaluate the possibility of deriving an RfD for methylmercury, specifically for the case of fish ingestion, on the basis of these new studies. In order to better support the risk-management decisions associated with developing a remediation approach for the site in question, the analysis was designed to provide information on the distribution of acceptable ingestion rates across a population, which could reasonably be expected to be consistent with the results of the epidemiological studies of other fish-eating populations. Based on a review of the available literature on the effects of methylmercury, a study conducted with a population in the Seychelles Islands was selected as the critical study for this analysis. The exposures to methylmercury in this population result from chronic, multigenerational ingestion of contaminated fish. This prospective study was carefully conducted and analyzed, included a large cohort of mother-infant pairs, and was relatively free of confounding factors. The results of this study are essentially negative, and a no-observed-adverse effect level (NOAEL) derived from the estimated exposures has recently been used by the Agency for Toxic Substances and Disease Registry (ATSDR) as the basis for a chronic oral minimal risk level (MRL) for methylmercury. In spite of the fact that no statistically significant effects were observed in this study, the data as reported are suitable for dose-response analysis using the BMD method. Evaluation of the BMD method used in this analysis, as well as in the current USEPA RfD, has demonstrated that the resulting 95% lower bound on the 10% benchmark dose (BMDL) represents a conservative estimate of the traditional NOAEL, and that it is superior to the use of "average" or "grouped" exposure estimates when dose-response information is available, as is the case for the Seychelles study. A more recent study in the Faroe Islands, which did report statistically significant associations between methylmercury exposure and neurological effects, could not be used for dose-response modeling due to inadequate reporting of the data and confounding from co-exposure to polychlorinated biphenyls (PCBs). BMD modeling over the wide range of neurological endpoints reported in the Seychelles study yielded a lowest BMDL for methylmercury in maternal hair of 21 ppm. This BMDL was then converted to an expected distribution of daily ingestion rates across a population using Monte Carlo analysis with a physiologically based pharmacokinetic (PBPK) model to evaluate the impact of interindividual variability. The resulting distribution of ingestion rates at the BMDL had a geometric mean of 1.60 microg/kg/day with a geometric standard deviation of 1.33; the 1st, 5th, and 10th percentiles of the distribution were 0.86, 1.04, and 1.15 microg/kg/day. In place of the use of an uncertainty factor of 3 for pharmacokinetic variability, as is done in the current RfD, one of these lower percentiles of the daily ingestion rate distribution provides a scientifically based, conservative basis for taking into consideration the impact of pharmacokinetic variability across the population. On the other hand, it was felt that an uncertainty factor of 3 for database limitations should be used in the current analysis. Although there can be high confidence in the benchmark-estimated NOAEL of 21 ppm in the Seychelles study, some results in the New Zealand and Faroe Islands studies could be construed to suggest the possibility of effects at maternal hair concentrations below 10 ppm. In addition, while concerns regarding the possibility of chronic sequelae are not supported by the available data, neither can they be absolutely ruled out. The use of an uncertainty factor of 3 is equivalent to using a NOAEL of 7 ppm in maternal hair, which provides additional protection against the possibility that effects could occur at lower concentrations in some populations. Based on the analysis described above, the distribution of acceptable daily ingestion rates (RfDs) recommended to serve as the basis for site-specific risk-management decisions at Alcoa's Point Comfort Operations ranges from approximately 0.3 to 1.1 microg/kg/day, with a population median (50th percentile) of 0.5 microg/kg/day. By analogy with USEPA guidelines for the use of percentiles in applications of distributions in exposure assessments, the 10th percentile provides a reasonably conservative measure. On this basis, a site-specific RfD of 0.4 microg/kg/day is recommended. PMID- 11762929 TI - Nails in the coffin: increasing evidence for the role of rheumatic disease in the cardiovascular mortality of rheumatoid arthritis. PMID- 11762930 TI - Examining health disparities in systemic lupus erythematosus. PMID- 11762931 TI - Immunoglobulin variable-region gene usage in systemic autoimmune diseases. PMID- 11762932 TI - Inflammatory bowel disease and spondylarthropathy. PMID- 11762933 TI - High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. AB - OBJECTIVE: To compare the incidence of cardiovascular (CV) events in persons with rheumatoid arthritis (RA) with that in people from the general population, adjusting for traditional CV risk factors. METHODS: Two hundred thirty-six consecutive patients with RA were assessed for the 1-year occurrence of 1) CV related hospitalizations, including myocardial infarction, stroke or other arterial occlusive events, or arterial revascularization procedures, or 2) CV deaths. Both outcomes were ascertained by medical records or death certificates. For comparison, we used CV events that occurred during an 8-year period among participants in an epidemiologic study of atherosclerosis and CV disease who were ages 25-65 years at study entry. We calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. RESULTS: Of the 236 RA patients, 234 were observed for 252 patient-years, during which 15 CV events occurred. Of these, 7 incident events occurred during the 204 patient years contributed by patients ages 25-65 years, for an incidence of 3.43 per 100 patient-years. In the comparison cohort, 4,635 community-dwelling persons were followed up for 33,881 person-years, during which 200 new events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 (95% confidence interval [95% CI] 1.86 8.43). After adjusting for CV risk factors using Poisson regression, the IRR decreased slightly, to 3.17 (95% CI 1.33-6.36). CONCLUSION: The increased incidence of CV events in RA patients is independent of traditional CV risk factors. This suggests that additional mechanisms are responsible for CV disease in RA. Physicians who provide care to individuals with RA should be aware of their increased risk of CV events and implement appropriate diagnostic and therapeutic measures. PMID- 11762934 TI - Long-term morbidity, mortality, and economics of rheumatoid arthritis. AB - OBJECTIVE: To estimate the morbidity, mortality, and lifetime costs of care for rheumatoid arthritis (RA). METHODS: We developed a Markov model based on the Arthritis, Rheumatism, and Aging Medical Information System Post-Marketing Surveillance Program cohort, involving 4,258 consecutively enrolled RA patients who were followed up for 17,085 patient-years. Markov states of health were based on drug treatment and Health Assessment Questionnaire scores. Costs were based on resource utilization, and utilities were based on visual analog scale-based general health scores. RESULTS: The cohort had a mean age of 57 years, 76.4% were women, and the mean duration of disease was 11.8 years. Compared with a life expectancy of 22.0 years for the general population, this cohort had a life expectancy of 18.6 years and 11.3 quality-adjusted life years. Lifetime direct medical care costs were estimated to be $93,296. Higher costs were associated with higher disability scores. CONCLUSION: A Markov model can be used to estimate lifelong morbidity, mortality, and costs associated with RA, providing a context in which to consider the potential value of new therapies for the disease. PMID- 11762935 TI - Selective lymphocyte chemokine receptor expression in the rheumatoid joint. AB - OBJECTIVE: In patients with rheumatoid arthritis (RA), chemokines and their receptors are important for lymphocyte trafficking into the inflamed joint. This study was undertaken to characterize the expression of chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CXCR3, and CX3CR1 in normal (NL) peripheral blood (PB), RA PB, and RA synovial fluid (SF). METHODS: Using flow cytometry, immunohistochemistry, and 2-color immunofluorescence, we defined the expression of chemokine receptors on CD3+ T lymphocytes in RA synovial tissue (ST), RA SF, RA PB, and NL PB. RESULTS: The percentage of CD3+ lymphocytes expressing CCR2, CCR4, CCR5, and CX3CR1 was significantly elevated in RA PB compared with that in NL PB, while the percentage of CD3+ lymphocytes expressing CCR5 was significantly enhanced in RA SF compared with that in NL and RA PB. In contrast, similar percentages of CD3+ lymphocytes in NL PB, RA PB, and RA SF expressed CCR6 and CXCR3. Immunohistochemistry of RA ST showed lymphocyte expression of CCR4, and 2 color immunofluorescence staining revealed RA ST CD3+ lymphocytes intensely immunoreactive for CXCR3, suggesting that these 2 receptors may be particularly important for CD3+ lymphocyte trafficking to the inflamed joint. In comparisons of chemokine receptor expression on naive (CD45RA+) and memory (CD45RO+) CD3+ lymphocytes, there were greater percentages of memory CD3+/CD4+ lymphocytes expressing CCR4, CCR5, and CXCR3 than naive CD3+/CD4+ lymphocytes in RA PB and RA SF, and greater percentages of memory CD3+/CD8+ lymphocytes expressing CCR4, CCR5, and CXCR3 than naive CD3+/CD8+ lymphocytes in RA SF, suggesting receptor up regulation upon lymphocyte activation. In contrast, percentages of CD3+/CD8+ memory lymphocytes expressing CX3CR1 were significantly less than percentages of naive CD3+/CD8+ lymphocytes in RA PB, suggesting that this receptor may be down regulated upon lymphocyte activation. A major difference between the RA PB and NL PB groups was significantly more CCR4+ memory leukocytes and memory CCR5+/ CD3+/CD8+ lymphocytes in RA PB than NL PB, further suggesting that these receptors may be particularly important for lymphocyte homing to the RA joint. CONCLUSION: These results identify CCR4, CCR5, CXCR3, and CX3CR1 as critical chemokine receptors in RA. PMID- 11762936 TI - Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile. AB - OBJECTIVE: This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients. METHODS: Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]), and 5) secretory group IIA phospholipase A2 (sPLA2-IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG). RESULTS: RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA2-IIA, ICAM, CRP, Fb, TNFalpha, and IFNgamma compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (Kd) to GAG (mean +/- SD Kd 204+/-22.4 nM Apo B) than did LDL from control subjects (Kd 312+/-36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P < or = 0.004). In RA patients, a significant positive correlation was obtained between sPLA2-IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA2-IIA. CONCLUSION: These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients. PMID- 11762937 TI - The osteoprotegerin/receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand system in cartilage. AB - OBJECTIVE: The receptor activator of nuclear factor kappaB (RANK) is a member of the tumor necrosis factor receptor family. It is activated by the secreted or cell surface-bound RANK ligand (RANKL). Osteoprotegerin (OPG) is a soluble nonsignaling receptor for RANKL and interferes with RANK activation. This receptor-ligand system regulates the differentiation of osteoclasts and dendritic cells. The present study examined human articular cartilage for the expression of these molecules and the role of RANKL in the regulation of chondrocyte function. METHODS: Normal and osteoarthritic (OA) human articular cartilage was used for explant tissue culture or for isolation of chondrocytes and cell culture. Expression of RANK, RANKL, and OPG was analyzed by immunohistochemistry, Western blotting, or reverse transcription-polymerase chain reaction. Recombinant RANKL was added to cartilage or chondrocyte cultures, and gene expression, collagenase and nitric oxide production, and NF-kappaB activation were determined. RESULTS: RANK, RANKL, and OPG messenger RNA (mRNA) were expressed in normal cartilage. By immunohistochemistry, RANK, RANKL, and OPG were detected in the superficial zone of normal cartilage. OA cartilage contained increased levels of OPG mRNA, and expression of the 3 proteins extended into the midzone of OA cartilage. OPG was detected by Western blotting, and was increased in response to interleukin-1beta stimulation. OPG, RANK, and RANKL protein were also detected in cultured chondrocytes. Addition of exogenous RANKL did not activate NF-kappaB, induce expression of genes encoding proinflammatory mediators in chondrocytes, or stimulate the production of collagenase and nitric oxide. CONCLUSION: These results demonstrate the expression of OPG, RANK, and RANKL in cartilage. However, RANKL does not activate human articular chondrocytes. PMID- 11762938 TI - Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology. AB - OBJECTIVE: To understand changes in gene expression levels that occur during osteoarthritic (OA) cartilage degeneration, using complementary DNA (cDNA)-array technology. METHODS: Nine normal, 6 early degenerated, and 6 late-stage OA cartilage samples of human knee joints were analyzed using the Human Cancer 1.2 cDNA array and TaqMan analysis. RESULTS: In addition to a large variability of expression levels between different patients, significant expression patterns were detectable for many genes. Cartilage types II and VI collagen were strongly expressed in late-stage specimens, reflecting the high matrix-remodeling activity of advanced OA cartilage. The increase in fibronectin expression in early degeneration suggests that fibronectin is a crucial regulator of matrix turnover activity of chondrocytes during early disease development. Of the matrix metalloproteinases (MMPs), MMP-3 appeared to be strongly expressed in normal and early degenerative cartilage and down-regulated in the late stages of disease. This indicates that other degradation pathways might be more important in late stages of cartilage degeneration, involving other enzymes, such as MMP-2 and MMP 11, both of which were up-regulated in late-stage disease. MMP-11 was up regulated in OA chondrocytes and, interestingly, also in the early-stage samples. Neither MMP-1 nor MMP-8 was detectable, and MMP-13 and MMP-2 were significantly detectable only in late-stage specimens, suggesting that early stages are characterized more by degradation of other matrix components, such as aggrecan and other noncollagenous molecules, than by degradation of type II collagen fibers. CONCLUSION: This investigation allowed us to identify gene expression profiles of the disease process and to get new insights into disease mechanisms, for example, to develop a picture of matrix proteinases that are differentially involved in different phases of the disease process. PMID- 11762939 TI - Activation of the inducible nitric oxide synthase pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. AB - OBJECTIVE: Osteoporosis is a major clinical problem in chronic inflammatory diseases such as rheumatoid arthritis. The mechanism of bone loss in this condition remains unclear, but previous studies have indicated that depressed bone formation plays a causal role. Since cytokine-induced nitric oxide (NO) production has been shown to inhibit osteoblast growth and differentiation in vitro, this study was undertaken to investigate the role of the inducible NO synthase (iNOS) pathway in the pathogenesis of inflammation-mediated osteoporosis (IMO) by studying mice with targeted inactivation of the iNOS gene (iNOS knockout [iNOS KO] mice). METHODS: IMO was induced in wild-type (WT) and iNOS KO mice by subcutaneous injections of magnesium silicate. The skeletal response was assessed at the tibial metaphysis by measurements of bone mineral density (BMD), using peripheral quantitative computed tomography, by bone histomorphometry, and by measurements of bone cell apoptosis. RESULTS: NO production increased 2.5-fold (P < 0.005) in WT mice with IMO, but did not change significantly in iNOS KO mice. Total BMD values decreased by a mean +/- SEM of 14.4+/-2.0% in WT mice with IMO, compared with a decrease of 8.6+/-1.2% in iNOS KO mice with IMO (P < 0.01). Histomorphometric analysis confirmed that trabecular bone volume was lower in WT mice with IMO compared with iNOS KO mice with IMO (16.2+/-1.5% versus 23.4+/ 2.6%; P < 0.05) and showed that IMO was associated with reduced bone formation and a 320% increase in osteoblast apoptosis (P < 0.005) in WT mice. In contrast, iNOS KO mice with IMO showed less inhibition of bone formation than WT mice and showed no significant increase in osteoblast apoptosis. CONCLUSION: Inducible NOS mediated osteoblast apoptosis and depressed bone formation play important roles in the pathogenesis of IMO. PMID- 11762940 TI - Systemic lupus erythematosus in three ethnic groups. IX. Differences in damage accrual. AB - OBJECTIVE: To determine the factors predictive of damage in a multiethnic (Hispanic, African American, and Caucasian) LUMINA (lupus in minority populations, nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) with disease duration of < or =5 years at enrollment (T0). METHODS: Variables (socioeconomic/demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at T0 and annually thereafter. Disease damage was measured with the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and disease activity was measured with the Systemic Lupus Activity Measure. The relationship between the different variables and the SDI at the last visit (TL) was examined (mean followup from diagnosis to TL 61 months; adjusted for disease duration). Poisson regression was used to identify the independent association between the different variables and SDI scores at TL. RESULTS: Seventy-two Hispanics, 104 African Americans, and 82 Caucasians were included. One-half of patients had not accrued any damage. Caucasians had the lowest SDI scores at T0, and Hispanics had the highest scores at TL. Renal damage occurred more frequently among Hispanics and African Americans, while integument damage was more frequent among African Americans. Neuropsychiatric (20%), renal (16%), and ocular (15%) damage occurred most frequently among all patients. Independent predictors of SDI at TL were age, corticosteroid use (maximum dose at T0), number of American College of Rheumatology (ACR) criteria met, disease activity, and abnormal illness-related behaviors. Other variables were less consistently associated with damage accrual (poverty in African Americans, lack of HLA-DRB1*0301 in Hispanics, presence of HLA-DQB1*0201 and acute onset of SLE in Caucasians). CONCLUSION: Damage in SLE occurs from the outset in some, but not all, patients; Hispanics accrue damage more rapidly. Disease factors (corticosteroid use, number of ACR criteria met, disease activity, and acute-onset type) are important, but age and abnormal illness-related behaviors also contribute to overall damage in SLE. PMID- 11762941 TI - Linkage analysis of human systemic lupus erythematosus-related traits: a principal component approach. AB - OBJECTIVE: To identify chromosomal regions containing genes involved in the susceptibility to human systemic lupus erythematosus (SLE)-related traits. METHODS: In the context of a genome scan, we analyzed 101 SLE-affected sibpairs with respect to dermatologic, renal, immunologic, hematologic, neurologic, cardiopulmonary, and arthritic characteristics. Phenotypes were redefined in terms of principal components, which are synthetic variables composed of linear combinations of the original traits. Using 9 principal components obtained from these 7 traits plus age at SLE onset and race, we analyzed genome scan data with the multivariate version of the new Haseman-Elston regression model. RESULTS: The largest linkage for an individual trait was on chromosome 2 at 228 cM (immunologic; P = 0.00048). The most significant linkage to an individual principal component was on chromosome 4 at 208 cM (P = 0.00007). The largest multivariate linkage was on chromosome 7 at 69 cM (P = 0.0001). Of the individual organ systems, dermatologic involvement had the largest effect (P = 0.0083) at this peak at 7p13 on chromosome 7. Further analyses revealed that malar rash, a subtype of dermatologic involvement, was linked significantly (P = 0.00458) to this location. CONCLUSION: These results provide evidence of the presence and locations of genes that are involved in the genetic susceptibility to SLE-related traits in humans. PMID- 11762942 TI - Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis. AB - OBJECTIVE: To investigate whether a polymorphism(s) or mutation(s) in the tumor necrosis factor receptor II (TNFRII) gene is involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: All 10 exons of the TNFRII gene were analyzed by exon-specific polymerase chain reaction-single-strand conformation polymorphism, followed by nucleotide sequencing of exons that displayed aberrant bands. To analyze the function of the TNFRII polymorphisms, the full-length TNFRII complementary DNA of each allele was transfected in HeLa cells and then studied for specific binding of 125I-TNFalpha, as well as interleukin-6 (IL-6) production and cytotoxic activity after treatment with recombinant human TNFalpha. RESULTS: We identified 4 polymorphisms, at codons 56, 181, 196, and 232. The latter 2 had amino acid substitutions M196R and E232K, respectively. Only the 196R allele was significantly associated with SLE in our 105 Japanese SLE patients, with an allele frequency of 20.5%, compared with 12.6% in 99 healthy controls (P = 0.0335). More importantly, using TNFRII-transfected HeLa cells, we demonstrated significantly increased IL-6 production by 196R TNFRII compared with 196M TNFRII. The cytotoxic activity induced by 196R TNFRII was also increased compared with that of 196M TNFRII. This increase was achieved without affecting the binding affinity of TNFalpha to TNF-RII, as demonstrated by the finding that specific TNFalpha binding to the HeLa transfectants of 196R and 196M TNFRII was similar, with Kd values of 3.12 x 10(-10)M and 4.34 x 10(-10)M, respectively. CONCLUSION: These results suggest that 196R TNFRII, which transduces the signals of TNFalpha more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE. PMID- 11762943 TI - Improvement in skin thickening in systemic sclerosis associated with improved survival. AB - OBJECTIVE: The natural history of changes in skin thickening in diffuse scleroderma is quite variable, but the significance of these changes is not clear. Clinical trials are using changes in skin thickening as the primary outcome measure, and thus it would be helpful to determine the significance of improvement in skin thickening. The purpose of the present study was to determine whether improvement in skin thickening over time was associated with improved survival. METHODS: Patients with early (<3 years) diffuse scleroderma who had a baseline evaluation and a repeat skin assessment (modified Rodnan skin score) performed 2 years later (i.e., they had to live for 2 years) were identified from the prospective, observational Pittsburgh Scleroderma Databank. The percentage of improvement and rate of change in the skin score during that time were determined. Patients with an improvement in their skin thickening of >25% of their peak skin score and a rate of change of at least 5 units/year were defined as the improved group; patients with increased skin thickening or no improvement were termed the no improvement group. Demographic and clinical features, organ system involvement, and survival rates were determined and the groups were compared. Regression and Cox regression analyses were used to determine what features were associated with improved skin thickness and survival. RESULTS: Two hundred seventy-eight patients fulfilled the entry criteria, 63% in the improved group and 36% in the no improvement group. The groups were similar in terms of clinical and demographic characteristics at the initial visit. The improved group had an average improvement of 50% of their peak skin score at 2 years after the initial visit. Survival was significantly better in the improved group compared with the unimproved group at 5 and 10 years, with rates of 90% and 80%, respectively, in the improved group and 77% and 60%, respectively, in the no improvement group (P < 0.0001). There were no significant differences in the occurrence of severe organ involvement during the first 2 years to account for the later differences in survival. The duration of the use of D-penicillamine was significantly associated with improved skin thickness and improved survival. CONCLUSION: Among patients surviving the first few years of diffuse scleroderma, striking improvement in skin thickening may occur in up to two-thirds. This improvement in skin thickening is associated with improved survival. Improvement in skin thickening may be useful as a surrogate for improvement in survival in clinical trials. PMID- 11762944 TI - Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. AB - We report on the successful, compassionate use of the anti-CD20 chimeric monoclonal antibody rituximab in a patient with chronic, relapsing cytoplasmic antineutrophil cytoplasmic antibody (cANCA)-associated Wegener's granulomatosis (WG). The patient initially responded to treatment with glucocorticoids and cyclophosphamide. However, bone marrow toxicity during cyclophosphamide treatment of a relapse precluded its further use. Azathioprine and mycophenolate mofetil treatment had failed to maintain remission of the WG, and methotrexate was contraindicated. Because the patient's 5-year course was characterized by close correlation of cANCA levels with disease activity, selective elimination of cANCA was deemed a treatment option for his latest relapse. He was given 4 infusions of 375 mg/M2 of rituximab and high-dose glucocorticoids. Complete remission was associated with the disappearance of B lymphocytes and cANCA. Glucocorticoid treatment was then discontinued. After 11 months, the cANCA recurred, and rituximab therapy was repeated, without glucocorticoids. At 8 months after the second course of rituximab (18 months after the first course), the patient's WG has remained in complete remission. Elimination of B cells by rituximab therapy may prove to be an effective and safe new treatment modality for ANCA-associated vasculitis and possibly other autoimmune diseases. This modality warrants closer examination in a carefully conducted clinical trial. PMID- 11762945 TI - PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. AB - OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis. PMID- 11762946 TI - Antineutrophil cytoplasmic antibodies stabilize adhesion and promote migration of flowing neutrophils on endothelial cells. AB - OBJECTIVE: Recruitment of neutrophils to sites of inflammation requires coordinated regulation of their capture, activation, and migration on vascular endothelium. This study examines whether exposure of neutrophils to antineutrophil cytoplasmic antibodies (ANCAs) can disrupt this sequence of events. METHODS: Isolated human neutrophils were perfused in the presence or absence of ANCA-positive IgG over endothelial cells that had been activated with either 2 units/ml or 100 units/ml of tumor necrosis factor alpha (TNFalpha) for 4 hours. RESULTS: When endothelial cells were activated with 100 units/ml of TNFalpha, neutrophils were captured from flow, a small proportion of adherent cells rolled, and the majority transmigrated through the endothelial cell monolayer. When neutrophils were treated with ANCA IgG immediately before, 5 minutes before, or 15 minutes before perfusion, none rolled on contact with the endothelium, but the majority still transmigrated. When endothelial cells were activated with 2 units/ml of TNFalpha, the majority of untreated adherent neutrophils rolled, a few transmigrated, and the number that attached decreased with time during washout. In contrast, when neutrophils were pretreated with ANCA IgG just before perfusion, adhesion was stabilized, and the number of neutrophils that transmigrated was increased 10-fold. Priming of the neutrophils with TNFalpha before the addition of ANCA further increased the stability of neutrophil binding, but did not significantly increase transmigration. CONCLUSION: Rather than frustrating the transmigration process, ANCAs promoted the migration of neutrophils through the endothelium. That the effect was evident at a relatively low level of endothelial activation suggests that ANCAs may potentiate the early vasculitic lesion and promote tissue damage and recruitment of other proinflammatory cells. PMID- 11762947 TI - Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. AB - OBJECTIVE: To review the occurrence of neurologic events suggestive of demyelination during anti-tumor necrosis factor alpha (anti-TNFalpha) therapy for inflammatory arthritides. METHODS: The Adverse Events Reporting System of the Food and Drug Administration (FDA) was queried following a report of a patient with refractory rheumatoid arthritis who developed confusion and difficulty with walking after receiving etanercept for 4 months. RESULTS: Nineteen patients with similar neurologic events were identified from the FDA database, 17 following etanercept administration and 2 following infliximab administration for inflammatory arthritis. All neurologic events were temporally related to anti TNFalpha therapy, with partial or complete resolution on discontinuation. One patient exhibited a positive rechallenge phenomenon. CONCLUSION: Further surveillance and studies are required to better define risk factors for and frequency of adverse events and their relationship to anti-TNFalpha therapies. Until more long-term safety data are available, consideration should be given to avoiding anti-TNFalpha therapy in patients with preexisting multiple sclerosis and to discontinuing anti-TNFalpha therapy immediately when new neurologic signs and symptoms occur, pending an appropriate evaluation. PMID- 11762948 TI - Statins prevent endothelial cell activation induced by antiphospholipid (anti beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. AB - OBJECTIVE: To investigate the ability of statins, the inhibitors of the hydroxymethylglutaryl-coenzyme A reductase enzyme, to affect endothelial cell activation induced by anti-beta2-glycoprotein I (anti-beta2GPI) antibodies in vitro. METHODS: Human umbilical vein endothelial cell (HUVEC) activation was evaluated as U937 monocyte adhesion, E-selectin, and intercellular adhesion molecule I (ICAM-1) expression by cell enzyme-linked immunosorbent assay and as interleukin-6 (IL-6) messenger RNA (mRNA) expression by RNA protection assay. E selectin-specific nuclear factor kappaB (NF-kappaB) DNA-binding activity was evaluated by the gel-shift assay. HUVECs were activated by polyclonal affinity purified IgG, human monoclonal IgM anti-beta2GPI antibodies, human recombinant IL 1beta, tumor necrosis factor alpha, or lipopolysaccharide (LPS). RESULTS: Fluvastatin reduced, in a concentration-dependent manner (1-10 microM), the adhesion of U937 to HUVECs and the expression of E-selectin and ICAM-1 induced by anti-beta2GPI antibodies as well as by cytokines or LPS. Another lipophilic statin, simvastatin, displayed similar effects but to a lesser extent than fluvastatin. The inhibition of E-selectin expression exerted by fluvastatin was related to the impairment of NF-kappaB binding to DNA. Moreover, the drug attenuated the expression of IL-6 mRNA in HUVEC exposed to anti-beta2GPI antibodies or cytokines. Incubation of HUVECs with mevalonate (100 microM), concomitantly with fluvastatin, greatly prevented the inhibitory effect of statin. CONCLUSION: Endothelial activation mediated by anti-beta2GPI antibody can be inhibited by statins. Because of the suggested role of endothelial cell activation in the pathogenesis of antiphospholipid syndrome (APS), our data provide, for the first time, a rationale for using statins as an additional therapeutic tool in APS. PMID- 11762949 TI - TIA-1 regulates the production of tumor necrosis factor alpha in macrophages, but not in lymphocytes. AB - OBJECTIVE: To determine whether TIA-1 differentially regulates the production of tumor necrosis factor a (TNFalphalpha) in macrophages and lymphocytes. METHODS: Peritoneal macrophages derived from wild-type and TIA-1-/- mice were cultured in the absence or presence of lipopolysaccharide (LPS) before comparison of the production of TNFalpha protein by intracellular flow cytometry and the secretion of TNFalpha protein by enzyme-linked immunosorbent assay. In parallel experiments, splenocytes were cultured in the absence or presence of concanavalin A (Con A), phorbol myristate acetate (PMA)/ionomycin, or anti-CD3/anti-CD28 before comparing the production of TNFalpha protein. Finally, the relative expression of TIA-1 protein in macrophages and splenocytes was compared using immunoblotting analysis. RESULTS: LPS-activated peritoneal macrophages derived from TIA-1-/- mice produced significantly more TNFalpha than macrophages from wild-type controls. In contrast, splenic lymphocytes (CD3+, CD4+, or CD8+) derived from wild-type and TIA-1-/- mice produced similar amounts of TNFalpha in response to Con A, PMA/ionomycin, or anti-CD3/anti-CD28. Lymphocytes and macrophages expressed similar amounts of TIA-1 protein, indicating that differential expression of TIA-1 cannot account for these results. CONCLUSION: TIA-1 is the target of a regulatory pathway that operates in activated macrophages, but not in activated lymphocytes. Developing drugs that target this pathway might prevent the pathologic overexpression of TNFalpha without subverting the T lymphocyte response to microbial pathogens. PMID- 11762950 TI - Adenovirus-based overexpression of tissue inhibitor of metalloproteinases 1 reduces tissue damage in the joints of tumor necrosis factor alpha transgenic mice. AB - OBJECTIVE: Rheumatoid arthritis is a prototype of a destructive inflammatory disease. Inflammation triggered by the overexpression of tumor necrosis factor alpha (TNFalpha) is a driving force of this disorder and mediates tissue destruction. Since matrix metalloproteinases (MMPs) are among the molecules activated by TNFalpha, we hypothesized that overexpression of their natural inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), in TNFalpha transgenic mice could inhibit the development of destructive arthritis. METHODS: Systemic treatment was carried out by replication-defective adenoviral vectors for TIMP-1, beta-galactosidase, or phosphate buffered saline (PBS), which were applied once at the onset of arthritis. Clinical, serologic, radiologic, and histologic outcomes were assessed 18 days after the treatment. RESULTS: The AdTIMP-1 group showed significantly reduced paw swelling and increased grip strength compared with the 2 control groups, whereas total body weight, TNFalpha, and interleukin-6 levels were similar in all 3 groups. Radiographic assessment revealed a significant reduction of joint destruction in the AdTIMP-1 group; this was confirmed by histologic analyses showing reduced formation of pannus and erosions in the AdTIMP-1 group compared with the AdLacZ and PBS control groups. The formation of arthritis-specific autoantibodies to heterogeneous nuclear RNP A2 was not observed in the AdTIMP-1 group but was present in the 2 control groups. CONCLUSION: These results indicate a central role of MMPs in TNFalpha mediated tissue damage in vivo and a promising therapeutic role for TIMP-1. PMID- 11762951 TI - Differential expression pattern of the antiapoptotic proteins, Bcl-2 and FLIP, in experimental arthritis. AB - OBJECTIVE: To examine the relationship between apoptosis and the expression of antiapoptotic proteins in the pathogenesis of experimental inflammatory arthritis. METHODS: Clinical and histologic assessment of adjuvant-induced arthritis (AIA) was performed over a 42-day period. The induction of apoptosis was measured by TUNEL analysis, and the antiapoptotic proteins, Bcl-2 and FLIP, were examined by immunohistochemistry with the use of monospecific antibodies. The percentage of Bcl-2- and FLIP-positive cells was correlated with histologic markers of AIA. RESULTS: Arthritis developed by day 14 following adjuvant injection. Few TUNEL-positive cells were observed between days 0 and 21, indicating that apoptosis did not occur at these time points. An increase in the number of TUNEL-positive cells was observed at day 28, particularly outside sites of cartilage or bone erosion, which dramatically declined by day 35. Immunohistochemical analyses of Bcl-2 and FLIP revealed that the synovium was positive for Bcl-2 and FLIP on day 0. On day 14, Bcl-2 was present at the sites of early erosions and correlated with the erosion and inflammation scores. FLIP was also highly expressed at sites of erosion and was localized to the pannus starting on day 21. Although TUNEL positivity peaked at day 28, a time point in which Bcl-2 and FLIP were present, the areas that displayed intense positivity for expression of Bcl-2 and FLIP were TUNEL negative. In addition, the number of neutrophils in the synovial lining and pannus significantly decreased from day 28 to day 35, suggesting that the cells undergoing apoptosis were neutrophils. Furthermore, at day 42 when TUNEL-positive cells were absent, Bcl-2 expression was diminished, while FLIP remained highly expressed in the pannus. CONCLUSION: The overall percentage of TUNEL-positive cells in the ankle was <1% except on days 28 and 35 post-adjuvant injection, suggesting that in AIA, similar to rheumatoid arthritis, a lack of apoptosis may contribute to disease progression. Furthermore, Bcl-2 and FLIP are temporally and differentially expressed during the pathogenesis of AIA. Inhibition of these molecules may augment synovial apoptosis and ameliorate the disease. PMID- 11762952 TI - Amelioration of joint disease in a rat model of collagen-induced arthritis by M40403, a superoxide dismutase mimetic. AB - OBJECTIVE: To investigate the effects of M40403, a synthetic mimetic of superoxide dismutase (SOD), on collagen-induced arthritis (CIA) in rats. METHODS: CIA was elicited in Lewis rats by intradermal injection of 100 microl of an emulsion of bovine type II collagen (CII) in Freund's incomplete adjuvant at the base of the tail. A second injection was given on day 21. RESULTS: Immunization induced an erosive arthritis of the hind paws. Macroscopic evidence of CIA first appeared as periarticular erythema and edema in the hind paws by days 24-26 after the first injection, with a 100% incidence by days 27. Severity progressed over a 35-day period. Radiography revealed soft tissue swelling and focal resorption of bone, together with osteophyte formation in the tibiotarsal joint. Histopathologic features included erosion of the articular cartilage at the joint margins and subchondral bone resorption associated with bone-derived multinucleated cell-containing granulomatous lesions. Treatment with M40403 (2-10 mg/kg/day) starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26-35 and improved the histologic findings in the joint and paw. Immunohistochemical analysis for nitrotyrosine (a marker of peroxynitrite formation) and poly(ADP-ribose) polymerase (PARP; a nuclear enzyme activated by DNA single-strand damage) revealed positive staining in the inflamed joints of CII-treated rats, suggestive of the formation of peroxynitrite and DNA damage, both of which were markedly reduced by M40403 treatment. Radiographic evidence of protection from bone resorption, osteophyte formation, and soft tissue swelling was apparent in the tibiotarsal joints of M40403-treated rats. Arthritic rats treated with M40403 gained weight at the same rate and to the same extent as normal, nonarthritic rats. CONCLUSION: This study shows that a low molecular weight mimetic of SOD, M40403, attenuates the degree of chronic inflammation, tissue damage, and bone damage associated with CIA in the rat, and supports the possible use of SOD mimetics as therapeutic agents for the management of chronic diseases such as rheumatoid arthritis. PMID- 11762953 TI - Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1 mice. AB - OBJECTIVE: To study the role of CD44, the principal hyaluronan (HA) receptor, in experimental arthritis. METHODS: We generated CD44 gene deficiency in arthritis susceptible DBA/1LacJ mice to study the role of CD44 directly in collagen-induced arthritis (CIA). Wild-type and CD44-deficient mice were immunized with chicken type II collagen, and the onset and severity of CIA were monitored up to day 64. The immune status of immunized mice was determined at the end of the experiments. Cell transfer experiments were performed to monitor lymphocyte traffic to the inflamed joints. RESULTS: Mice homozygous for the CD44 mutation developed normally and showed no phenotypic defects. Although they showed a normal response to immunization with type II collagen and had Th1/Th2 ratios comparable with those in wild-type animals, CD44-deficient mice exhibited significant reductions in both the incidence and severity of CIA. This was accompanied by altered serum levels of HA, reduced expression of L-selectin, and a delayed entry of intravenously injected CD44-deficient donor lymphocytes into the arthritic joints of recipient mice. CONCLUSION: While CD44 is not essential for morphogenesis and autoimmunity, this cell surface receptor seems to play an important role in the development of arthritis, most likely by directing leukocyte traffic to the site of inflammation. PMID- 11762954 TI - The impact of ultrasonography on diagnosis and management of patients with musculoskeletal conditions. PMID- 11762955 TI - Treatment of longstanding active giant cell arteritis with infliximab: report of four cases. PMID- 11762956 TI - Infliximab treatment of severe ankylosing spondylitis: one-year followup. PMID- 11762957 TI - Effects of anti-tumor necrosis factor alpha on synovium in patients with spondylarthropathy: comment on the article by Baeten et al. PMID- 11762958 TI - Possible infection with Brucella in patients with spondylitis: comment on the article by Brandt et al and the clinical images by Mercie and Leleu. PMID- 11762959 TI - Correlation among macrophage inflammatory protein 1alpha levels, matrix metalloproteinase 8 levels, and systemic inflammation in rheumatoid arthritis: comment on the articles by Yamanaka et al and Mattey et al. PMID- 11762960 TI - Reduced bone mineral density in men with rheumatoid arthritis: comment on the article by Haugeberg et al. PMID- 11762961 TI - Are cases of rheumatoid arthritis in smokers and lifelong nonsmokers representative of different rheumatoid disease processes? Comment on the article by Harrison et al. PMID- 11762962 TI - Disease activity and survival in vasculitis: comment on the article by Gayraud et al. PMID- 11762963 TI - Possible association between glucosamine treatment and renal toxicity: comment on the letter by Danao-Camara. PMID- 11762964 TI - Fetal cell trafficking and dermal fibrosis: comment on the article by Christner et al. PMID- 11762965 TI - Information supplied to cancer patients and their caregivers--no more unmet needs? PMID- 11762966 TI - Important drugs for cough in advanced cancer. AB - Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management. PMID- 11762967 TI - Taste and smell dysfunction in patients receiving chemotherapy: a review of current knowledge. AB - Disorders of taste are prevalent in patients undergoing chemotherapy and often have a negative impact on quality of life and nutrition. We now present a review of the physiology of taste and smell and a discussion of the multiple causes of disturbances in these senses in patients undergoing standard- and high-dose chemotherapy. A better understanding of the complex and often multifactorial etiology of taste dysfunction should enable the clinician to institute measures to minimize the impact of these disturbing changes. PMID- 11762968 TI - Voluntary associations for cancer patients in Sweden: supportive activities. AB - Our aim was to describe voluntary associations for patients with cancer in Sweden (n=108) and their activities, type and extent of member support, and the associations' collaboration with the health care system. A specially constructed questionnaire with structured and open questions was used for the investigation. The frequency of answers was 89%. The results show in the broadest sense that the associations have two missions. The direct patient-related mission concerns providing patients with support in the form of close proximity, approachability and through distribution of knowledge together with financial and practical support; the indirect patient-related mission deals with activities aimed at improving conditions for patients in general within the health care system and by influencing authorities as well as supporting family members and significant others and providing financing. The associations collaborate with the health care system, although they face difficulties in becoming 'sanctioned' and in establishing positive relationships with the health care community. The associations display a positive attitude towards their cause and the personal gratification that the voluntary work brings. In general, the findings indicate that the associations have a potential to help patients live and cope with their cancer disease. PMID- 11762969 TI - The informational needs, satisfaction with communication, and psychological status of primary caregivers of cancer patients receiving chemotherapy. AB - The first objective of the study was to identify the specific informational needs of primary caregivers of cancer patients receiving chemotherapy in a Greek outpatient setting and to assess their preference for cancer-specific booklets, their levels of satisfaction with communication and their psychological status. The second objective was to examine whether their need for information was associated with their preference for written information, level of satisfaction, and levels of psychological distress. The final objective was to search for possible associations between satisfaction and psychological distress. Seventy eight caregivers participated in the study and data were collected by structured individual interviews. The main findings to emerge were that a significant proportion of the caregivers had elevated needs for information, which were positively associated with a preference for cancer-specific printed material and negatively associated with satisfaction with the doctor's communication of information and affective behavior. Participants experienced heightened levels of anxiety and depression, which were independent of the need for information, preference for printed material or satisfaction with communication. The results suggest that the Greek cancer caregiver needs more factual information relevant to the patient's condition and that communication of information is critical if he or she is to be satisfied. The Greek oncologist should therefore not only try to detect the informational needs, but should also be qualified to meet them in the best possible way. In addition, the rates of anxiety and depression observed highlight the need for a more thorough evaluation and management of caregivers' psychological morbidity in the Greek oncology setting. PMID- 11762970 TI - The significant unmet needs of cancer patients: probing psychosocial concerns. AB - 'Significant unmet needs' are those needs that patients identify as both important and unsatisfied. In this article we ask whether the overall needs of cancer patients are actually being met. We believe that the range of unmet need, and the kinds of patients who are more likely to claim unmet need, should be carefully identified. The needs responses of a series of 295 cancer patients in a cross-sectional survey were analysed. The majority expressed the opinion that information and good relationships with health care professionals were important, and few expressed dissatisfaction with these aspects of need. Similarly, needs items about support from family and friends were largely rated as important and satisfied. For a sizeable minority of patients, items of significant unmet need cluster around aspects of managing daily life, emotions, and social identity. The distribution of significant unmet needs is not random but is more likely to be experienced by patients who are younger, have a long-standing illness or disability, do not own/have use of a car, and/or have no religious faith. Furthermore, significant unmet needs relate to patients' ability to talk freely to a carer about the cancer, the degree to which the cancer interferes with social activities, and whether financial difficulties are experienced. Most of the significant unmet need is beyond the remit of services primarily designed for the treatment of disease. We consider whether multidisciplinary cancer teams can be expected to deal with all aspects of the cancer experience. PMID- 11762971 TI - Effectiveness of a teaching programme in pain and symptom management for junior house officers. AB - The objectives of this study were (i) to assess the level of knowledge with respect to pain and symptom management among doctors in their first year after graduation and (ii) to measure the impact of a structured teaching programme on their level of knowledge. All 34 newly qualified junior house officers in one teaching hospital were offered a six-session teaching programme in pain and symptom management. A multiple-choice questionnaire was used to assess their level of knowledge at the beginning and at the end of a 6-month period over which the teaching sessions took place. Attendance at and satisfaction with the programme were high. There was a significant improvement in the level of knowledge at the end of the programme, with the greatest improvement in those who attended most sessions. The low scores recorded for the questionnaire administered before the teaching programme suggest that there is a critical need for improved education in palliative care amongst newly qualified doctors. We have shown that a simple in-service case-based teaching programme can meet this need effectively. PMID- 11762972 TI - Implementing evidence based antiemetic guidelines in the oncology setting: results of a 4-month prospective intervention study. AB - There is a considerable gap between obtaining results in randomized trials and implementing them into practice. This is particularly relevant with the high-cost 5HT3 antiemetics, which include ondansetron, dolasetron and granisetron. Randomized trial data suggests that they should be used as a single daily dose during only the first 24 h of chemotherapy because they offer little benefit over less costly agents beyond this period. In this study, six intervention methods (i.e. multifaceted approach) were combined to change physicians' 5HT3 prescribing patterns to comply with evidence-based antiemetic guidelines. A six-step implementation process was adopted, consisting of guideline dissemination, the use of opinion leaders, interactive educational workshops, therapeutic reminders in the form of preprinted orders, clinical interventions by pharmacists for the event of inappropriate antiemetic orders, and physician audit and feedback. Once implemented, the control of emesis was collected in all patients who were enrolled in the intervention program. Multivariable regression analysis was then used to assess whether prescribing within antiemetic guidelines compromised patient care. A total of 195 inpatients were enrolled in the study over the 4 month intervention period. Overall, 88.7% of granisetron prescriptions fulfilled the guidelines with respect to appropriate indication, dosage, and duration of therapy. The multivariable analysis suggested that granisetron prescribing within guidelines did not compromise the control of acute and delayed emesis. In addition, patients who received evidence-based antiemetic therapy experienced a significant reduction in the severity of acute nausea [risk ratio (RR) = 0.69; P=0.03]. The results of this guideline implementation study revealed that a pharmacist-driven multifaceted intervention program for such high-cost agents as 5HT3 antiemetics can promote their use in a clinically appropriate manner and can save unnecessary drug costs without compromising the quality of patient care. PMID- 11762973 TI - Outpatient parenteral antibiotic therapy in patients with haematological malignancies. A pilot study of an early discharge strategy. AB - The objectives of this study were to estimate the feasibility of a self administration outpatient parenteral antibiotic therapy (OPAT) model. to record the complication rate and to estimate patient acceptance during the OPAT period in patients with acute leukaemia (AL) or aggressive non-Hodgkin lymphoma (NHL). Patients were trained to administer the antibiotic infusions themselves, via their central venous access device, according to a checklist and step-by-step instructions. Study-specific questionnaires were used to evaluate patient acceptance. Eleven patients [AL (n=8) and NHL (n=3), median age 51 years, range 29-661 participated in the education programme and subsequent OPAT during ten episodes of documented infection and six episodes of fever of unknown aetiology. All patients had assessment of the infectious episode and initial parenteral antibiotic therapy in the hospital before they continued self-administration at home. The median education time was 3 h (range 0.75-4.5). The patients could stay at home for 4 days (median, range; 1-12) with ongoing intravenous antibiotic therapy instead of being hospitalised. None of the patients developed recurrent fever. All patients reported that OPAT was of great value and they would favour OPAT again during subsequent antibiotic therapy. In conclusion, the results of this pilot series suggest that OPAT, in this setting, is a safe alternative during the last days of an episode of fever / infection. All patients were satisfied overall, and none was readmitted. PMID- 11762974 TI - Existential support in brain tumour patients and their spouses. AB - Caring for patients with brain tumours raises existential questions. The aims of this study were to describe the opinions of nurses, patients and next-of-kin on existential support and how this is prioritised. PATIENTS AND METHOD: a total of 20 brain tumour patients, 16 family members and 16 nurses underwent explorative, tape-recorded, semi-structured interviews about existential issues. RESULTS: the nurses' opinions about the importance and prioritisation of existential support could be divided into four main groups: 1) religion, 2) "a diffuse picture", 3) conversation, and 4) questions of vital importance. They generally had a favourable attitude towards existential issues but thought those issues were difficult to deal with in practice due to lack of time, lack of knowledge and fear. Without exception, patients and family members were satisfied with the medical and physical treatment, but not with the existential support. They had, to a great extent, wished for existential support, and especially for the opportunity of talking about the existential threat that had arisen. Obstacles to this were thought to be due to the staff being under much stress, being afraid and unskilled. The importance of closeness and presence, which decreased existential isolation, was emphasised. PMID- 11762975 TI - Lymphoedema care of breast cancer patients in a breast care clinic: a survey of knowledge and health practice. AB - Lymphoedema, an accumulation of protein-rich fluid in interstitial tissue, is a well-recognised life-altering result of breast cancer treatment. With the goal of studying the prevalence and management of lymphoedema after breast cancer therapy, 171 patients were invited to complete a self-administered questionnaire following completion of treatment for breast cancer. The survey revealed that 82.5% of patients knew they were at-risk of developing lymphoedema. However, the level of knowledge about preventive care in lymphoedema was inadequate, with a mean score of 4.07 out of a full mark of 10 (SD=2.35, mode=2). A substantial proportion (45.6%; n=78) of respondents reported that they had experienced lymphoedema and subsequently developed multiple sites of lymphoedema, but only 34.7% (n=26) had been referred for physiotherapy. The study also revealed that patients who had received the combined regimen of mastectomy, lymph node dissection, radiotherapy and chemotherapy were at a higher risk of developing lymphoedema (chi2=6.305, P=0.043). Interestingly, it was found that nurses were the most frequently cited resource for information, but the least consulted professionals for discussion on treatment. It is apparent from our patient survey that there is a lack of knowledge on lymphoedema care amongst breast cancer patients. In order to improve patients' level of knowledge and their awareness of lymphoedema care, the provision for systematic and comprehensive patient education, including management protocols for lymphoedema, needs to be addressed. Education and training, will be essential components of efforts to ensure appropriate care for lymphoedema patients. PMID- 11762976 TI - Working with ambivalence: informal caregivers of patients at the end of life. AB - Informal caregivers of patients at the end of life perform a crucial role in maintaining and supporting patients at home. They provide a high level of demanding care, and as a consequence have been shown to have high-level information and support needs themselves. However, they are less often identified as recipients of services than as providers, and little research has addressed how services should be developed to meet their needs. This study aimed to address obstacles in the access to and provision of targeted, appropriate interventions. Eighteen informal carers participated in this qualitative study, which used a grounded approach to the analysis and generation of concepts. The data showed that while recognising their stress, anxiety and need for a caregivers' service, caregivers were highly ambivalent with regard to their own needs. The design and delivery of an intervention aimed at caregivers should take account of their high level of ambivalence by addressing their lack of identification with their role, enhancing existing coping strategies, and ensuring that interventions are accessible and acceptable. PMID- 11762977 TI - Methadone: the question or the answer for US opioid therapy and pharmaco economics? PMID- 11762978 TI - The changing picture of the HIV/AIDS epidemic. AB - Twenty years after it was first recognized, the HIV/AIDS epidemic continues to expand, but its impact varies greatly in different parts of the World. The worst of the epidemic is now centered in developing countries, especially sub-Saharan Africa, and areas such as Eastern Europe, which was only marginally involved a few years ago but has recently experienced the largest growth in the epidemic. In industrialized countries Highly Active Antiretroviral Therapy (HAART) has changed the natural history of HIV/AIDS, causing a reduction in mortality and morbidity due to HIV/AIDS and related diseases. Many interlocking factors determine the impact of HAART at the population level, including reduction of morbidity and mortality, changes in the natural history of HIV/AIDS and associated illnesses, and the effects of HAART on HIV transmission. To fully appreciate the potential benefits of HAART, the epidemic should continue to be monitored in the future, and the effects of HAART on reducing HIV transmission should also be evaluated. Interventions addressed to encourage the adoption of safer sex practices are badly needed, since a "rebound" in risky sexual behaviors was recently reported among high risk groups, which is, at least in part, attributable to the optimism about new treatments. PMID- 11762979 TI - "Tissue" transglutaminase expression in HIV-infected cells: an enzyme with an antiviral effect? AB - The cytopathic effect of HIV has been shown to be associated with the induction of apoptosis and the inhibition of proliferation of T cells. However, the cellular and molecular mechanisms at the basis of the dramatic immune cell loss caused by HIV in patients suffering from acquired immunodeficient syndrome (AIDS), are not yet fully established. We demonstrated that "tissue" transglutaminase (tTG) gene expression is induced in the immune system of seropositive individuals (peripheral blood mononuclear cells and lymph nodes). tTG is a multifunctional protein involved in a variety of fundamentally important cellular functions, in addition to cell death by apoptosis. The presence of high tTG levels in immune-competent cells of HIV+ persons might exert an important role in HIV-infection by influencing viral production. We propose that, in addition to its multiple functions, tTG might interfere with HIV replication by altering the viral mRNA trafficking between the nucleus and the cytoplasm. This effect might be due to its specific interaction with eIF5A, a cellular partner of HIV Rev protein, which is essential for HIV replication in immune-competent cells. Given the presence of high tTG levels in HIV+ individuals, it would be of interest to pursue the potential role of this multifunctional protein in the development of strategies aimed at the pharmacologic regulation of HIV production. PMID- 11762980 TI - Cardiomyopathy and encephalopathy in AIDS. AB - HIV encephalopathy has been in the past years the most typical CNS disorder in patients with AIDS. Histologic abnormalities consist in astrocytosis, myelin pallor, infiltration by infected macrophages, resident microglia and multinucleated giant cells, generally in absence of direct infection of neurons. Mononuclear phagocytes in the brain are the main target of HIV-1 infection and the site of productive viral replication, and viral stimulation leads to the release of neurotoxic products causing neurologic damage. Subclinical cardiac abnormalities are common in HIV+ patients and several studies suggested a role for cytokines and other inflammatory products as mediators of cardiac abnormalities. The common pathway for neurologic and cardiac manifestations supports the relationship between neurologic disease and cardiac dysfunction in HIV infection. Clinical observations suggest that cardiomyopathy could be associated with encephalopathy in HIV+ patients and that it may affect survival. Antiretroviral therapy may reduce impact of neurologic and cardiac abnormalities by suppressing plasma HIV-1 viral load. PMID- 11762981 TI - Epidemiology of cardiovascular involvement in HIV disease and AIDS. AB - The epidemiology of cardiac complications related to HIV including cardiomyopathy, increased left ventricular mass, myocarditis, pericardial effusion, endocarditis, and malignancy are discussed. A large number of HIV infected individuals will present with cardiac complications in the next decade as chronic viral infection, co-infections, drug therapy, and immunosuppression affect the heart. Understanding the nature and course of cardiac illness related to HIV infection will allow appropriate monitoring, early intervention and therapy, and will provide a baseline to evaluate the effects of new therapeutic regimens such as highly active antiretroviral therapy on the cardiovascular system. PMID- 11762982 TI - Cardiology and AIDS--HAART and the consequences. AB - Since the introduction of highly active antiretroviral therapy (HAART), AIDS has become a treatable disease. A steep decline in morbidity and mortality has been observed in most western countries. The HIV epidemic is now moving into middle aged populations which are already at increased risk for cardiovascular disease. Since the cardiovascular system is frequently affected in HIV infection, reflections on traditional cardiovascular risk factors is a pressing issue. Moreover, during the last few years, complex lipodystrophic body changes in association with metabolic abnormalities such as dyslipidemia and insulin resistance have become a common feature in HIV+ patients on HAART. Although the precise mechanisms are not fully understood, early reports on myocardial infarctions and vascular changes have raised concern about the possibility of an epidemic of cardiovascular events among HAART patients within the next decade. Not only more data on lipid-lowering drugs in the context of HAART, on switching strategies, and treatment interruptions, but also from intervention studies on traditional risk factors such as smoking, are urgently needed. In this review the key issues concerning cardiovascular aspects of HIV infection in the era of HAART and possible preventive strategies are discussed. PMID- 11762983 TI - HIV inhibitors: problems and reality. AB - The human immunodeficiency virus encodes three replication enzymes, which are required for a productive life-cycle. Currently, several anti-retroviral drugs are available for clinical use, and they are inhibitors of either the reverse transcriptase or the viral protease. The introduction of combination anti retroviral therapy (HAART) changed the prognosis of HIV infection. However, current therapy is not able to eradicate the virus, only suppress it; therefore, long-term use of the drugs is required to keep the viral load under control. Most of the problems associated with the HIV therapy are the consequence of the necessarily long-term use of the drugs. The long-term effectiveness of current inhibitors as therapeutic agents is limited by the rapid development of drug resistant variants. Furthermore, various side effects have been reported. These side effects include hypersensitivity, mitochondrial toxicity, lypodystrophy syndrome, insulin resistance and cardiovascular disorders. Further drug development is necessary to design new compounds that have efficacy similar to the currently used drugs in the management of HIV infection and that are potent against the resistant viruses but do not exhibit unwanted metabolic side effects. PMID- 11762984 TI - Apoptosis and the heart: a brief review. AB - Cardiomyopathies are observed with increasing frequency in association with AIDS and HIV infection. Although indirect evidence exists suggesting an association between apoptosis regulation and HIV infection, there is yet no direct evidence that HIV-associated cardiomyopathies involve increased level of apoptosis in the heart. However, since it is now known that apoptosis plays a significant role in heart injury associated with other conditions such as ischemia/reperfusion and heart failure, there is a possibility that dysregulation of apoptosis plays a similarly important role in HIV-associate cardiomyopathies. Here we will briefly review the evidence that apoptotic death of cardiomyocytes occurs and what novel therapeutic strategies may be suggested. PMID- 11762985 TI - Cardiac manifestations of HIV infection in infants and children. AB - Cardiac manifestations of HIV infection in children are common, but etiologies, contributing factors, and the natural history are largely unexplored. The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection Study (P2C2 HIV Study) was initiated in 1989 by the National Heart, Lung and Blood Institute, USA. A primary objective of this study is to examine the epidemiology of cardiovascular problems associated with HIV infection in a cohort of children vertically infected. Findings of the study thus far show that cardiovascular problems associated with HIV infection including left ventricular dysfunction and increased left ventricular mass are common and clinically important indicators of survival for children infected with HIV. PMID- 11762986 TI - Drugs and cardiotoxicity in HIV and AIDS. AB - The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a life-threatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug-related cardiac effects. PMID- 11762987 TI - Cardiovascular disease risk factors in HIV-infected patients in the HAART era. AB - HIV infection is accompanied by disturbances in lipid and glucose metabolism, which are further compounded by changes induced by antiretroviral drugs. There is increasing concern that these changes will lead to an epidemic of cardiovascular disease. Cardiovascular disease will no doubt increase, but current data indicate that the average absolute levels are likely to remain low, although patients with additional risks (smoking, hypertension, diabetes, age, family history, etc.) are certainly more susceptible. The complications of therapy need to be taken into account when deciding on the time of treatment, and reducing risk factors should become a routine aspect of the care of an HIV population that now lives longer as a result of highly active antiretroviral therapy. PMID- 11762988 TI - Metabolic and morphologic disorders in patients treated with highly active antiretroviral therapy since primary HIV infection. AB - Our objective was to describe morphologic and metabolic disorders in patients treated with highly active antiretroviral therapy (HAART) since primary HIV infection (PHI). Our method was prospective evaluation of patients with PHI initiating HAART at the time of diagnosis. Outcome measures were: development of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and of body shape abnormalities indicative of lipodystrophy, assessed through self-reported questionnaires and physical examination. RESULTS: From May 1997 to April 2001, 41 patients (35 males) with PHI presented at the National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy. A protease inhibitor-including regimen was started in 30 patients, and a nonnucleoside reverse transcriptase inhibitor in 11. Median interval between enrollment and treatment initiation was 30 days (mean 39, range 10-150). Median HAART duration was 19 months (mean 21.2, range 3-47). Thirty-eight patients had undetectable (less than 80 cp/mL) HIV RNA after a median of 3 months (mean 4.1, range 1-15). Mean CD4 cells count increased from 632/mmc at baseline to 936/mmc at the last follow up. No cases of hyperglycemia (glucose level greater than 110 mg/dL) were observed. After a median of 6 months on HAART, 10 patients developed beyond grade 2 (greater than 240 mg/dL) hypercholesterolemia, 5 developed beyond grade 2 (greater than 400 mg/dL) hypertrygliceridemia, and two developed both. Body mass index did not change significantly. Five patients (12.2%) developed lipodystrophy after a median of 14.5 months (mean 15.3, range 2-30), with an incidence of 7.3 per 100 patient-years. CONCLUSIONS: Dyslipidemia and lipodystrophy can occur in patients treated with HAART since PHI. This risk of should be taken into account when considering this early antiretroviral treatment of HIV infection. PMID- 11762989 TI - Clinical manifestation of HIV-related pulmonary hypertension. AB - In recent years, much more thought has been given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH), which currently represents one of the most severe events during HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnea that will progress to the point of breathlessness at rest. The diagnosis of HRPH can be made only after all etiologies for pulmonary hypertension have been excluded. Echocardiography has been proven to be an extremely useful tool for diagnosing HRPH, and Doppler echocardiography can be used to estimate systolic pulmonary artery pressure and to monitor the effects of therapy. Assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension, since vasoconstriction is a determinant characteristic of this disease. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new, more efficient antiretroviral treatment are introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV+ patients in the future. PMID- 11762990 TI - Pathological findings of HIV-associated cardiovascular disease. AB - More effective therapies have improved survival times of HIV+ patients, resulting in a higher prevalence of long-term complications of the disease. This review focuses on HIV-associated cardiovascular pathology, correlating the morphologic findings to clinical syndromes of HIV disease/AIDS. PMID- 11762991 TI - Cardiovascular monitoring and therapy for HIV-infected patients. AB - Cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients. These complications can usually be detected at subclinical levels with monitoring, which can help guide targeted interventions. This article reviews available data on types and frequency of cardiovascular manifestations in HIV+ patients and proposes monitoring strategies aimed at early subclinical detection. In particular, we recommend routine echocardiography for HIV+ patients, even those with no evidence of cardiovascular disease. We also review preventive and therapeutic cardiovascular interventions. For procedures that have not been studied in HIV+ patients, we extrapolate from evidence-based guidelines for the general population. PMID- 11762992 TI - Catheter-related bloodstream infections in HIV-infected patients. AB - Bloodstream infections (BSI) constitute a significant public health problem and represent an important cause of morbidity and mortality in hospitalized patients, with an approximate incidence of one episode per hundred hospital admissions. Studies on BSI in HIV+ patients have identified central venous catheters (CVC) as a risk factor, with an attributable mortality rate of 10-20%. The long-term CVC related infection risk appeared to be 5 to 10-fold higher with respect to the infection rates among HIV- patients. CVC associated infection rate ranges from 1.3 to 12 infections per 1,000 catheter-days. Staphylococcus aureus is the most common etiologic agent causative of CVC-related BSI, likely the result of the high skin and nasal carriage of this organism among HIV+ patients, mostly intravenous drug users. Coagulase-negative staphylococci are also frequently identified as cause of CVC-related BSI, likely the result of breaches in infection control measures and in antiseptic technique during CVC management. Treating bacteremia without catheter removal would be optimal, but the reported efficacy of systemic antibiotic therapy alone is only 25-32%. Conversely, recent studies have shown that, using an antibiotic-lock procedure, up to 90% of HIV infected and uninfected patients achieved complete eradication of catheter related BSIs without catheter removal. Clinical trials using new materials such as covalently linked heparin on the CVC surface, electrically charged CVC, novel topical agents that interfere with bacterial colonization, antiadhesin molecules and agents that block the gene expression involved in the biofilm formation, are all needed to reduce the high catheter-related infection risk among HIV+ patients. PMID- 11762993 TI - Risk of HIV and other blood-borne infections in the cardiac setting: patient-to provider and provider-to-patient transmission. AB - Health care workers (HCWs) face a well-recognized risk of acquiring blood-borne pathogens in their workplace, in particular hepatitis B and C viruses (HBV/HBC) and human immunodeficiency virus (HIV). Additionally, infected HCWs performing invasive exposure-prone procedures, including in the cardiac setting, represent a potential risk for patients. An increasing number of infected persons could need specific cardiac diagnostic procedures and surgical treatment in the future, regardless of their sex or age. The risk of acquiring HIV, HCV, HBV infection after a single at-risk exposure averages 0.5%, and 1-2%, and 4-30%, respectively. The frequency of percutaneous exposure ranges from 1 to 15 per 100 surgical interventions, with cardiothoracic surgery reporting the highest rates of exposures; mucocutaneous contamination by blood-splash occurs in 50% of cardiothoracic operations. In the Italian Surveillance (SIROH), a total of 987 percutaneous and 255 mucocutaneous exposures were reported in the cardiac setting; most occurred in cardiology units (46%), and in cardiovascular surgery (44%). Overall, 257 source patients were anti-HCV+, 54 HBsAg+, and 14 HIV+. No seroconversions were observed. In the literature, 14 outbreaks were reported documenting transmission of HBV from 12 infected HCWs to 107 patients, and 2 cases of HCV to 6 patients, during cardiothoracic surgery, especially related to sternotomy and its suturing. The transmission rate was estimated to be 5% to 13% for HBV, and 0.36% to 2.25% for HCV. Strategies in risk reduction include adequate surveillance, education, effective sharps disposal, personal protective equipment, safety devices, and innovative technology-based intraoperative procedures. PMID- 11762994 TI - Role of guidelines in clinical practice for the management of HIV-related diseases. AB - Several guidelines have been developed for the diagnosis, treatment and prevention of infectious diseases. Actually, evidence-based clinical practice guidelines provide physicians and other health care professionals with scientific information about the most appropriate strategy for the management of these patients, in order to avoid unnecessary or inappropriate interventions. As medical technology rapidly increases and becomes more complex, clinical guidelines can help health care providers to assess current practices and integrate new technological advances. Since AIDS was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of life for HIV+ patients. In this area, clinical guidelines have been developed to manage patient care, focusing on: antiretroviral therapy, prevention of opportunistic infections, and treatment of tuberculosis. The quality of the guideline is notable when appropriate methodologies are applied. Different methods for developing guidelines are evaluated here: Agency for Health Care Policy and Research (AHPCR) methodology is designed to produce evidence-based guidelines that are valid, clinically applicable, and flexible. Finally, the problems associated with the implementation of guidelines for HIV-related diseases and other infectious diseases are examined. PMID- 11762995 TI - AIDS cardiomyopathy: physiological, molecular, and biochemical studies in the transgenic mouse. AB - Cardiomyopathy in AIDS (AIDS CM) is an important and prevalent clinical problem. Mechanisms of AIDS CM are not completely understood. Among the potential etiologies of AIDS CM are HIV-1, various opportunistic infections, inflammatory reactions, cytokine effects, and cardiotoxicity of prescribed or illicit drugs. The transgenic mouse (TG) offers a unique in vivo way to elucidate mechanisms of AIDS CM. Structural and functional effects of HIV-1 and specific HIV-1 gene products on heart tissue can be addressed by TGs. Selective effects of HIV-1 and antiretroviral therapy may be defined in controlled studies. We utilized AIDS TGs with generalized expression of HIV-1 gene products in CM models. We treated those TGs with individual and combined antiretroviral therapeutics (HAART) to compare cardiovascular effects of AIDS per se and its therapy. We next developed cardiac specific TGs in which selected HIV-1 genes are driven by alpha-myosin heavy chain promoter to target the selected HIV-1 gene to the cardiac myocyte to define effects of specific HIV-1 gene products on the cardiac myocyte. Each transgenic approach is a model system that affords a distinct opportunity to explore the pathogenesis and pathophysiology of AIDS CM. PMID- 11762996 TI - Pathogenesis of HIV-associated cardiomyopathy. AB - Reviews and studies published before the introduction of highly active antiretroviral therapy (HAART) regimens have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults. HAART regimens have significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV+ subjects expected. However, early data raised concerns about HAART's being associated with an increase in both peripheral and coronary arterial diseases. A variety of potential etiologies have been postulated in HIV-related heart disease, including myocardial infection with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, drug related cardiotoxicity, nutritional deficiencies, and prolonged immunosuppression. In this review article we discuss HIV-associated cardiovascular complications, focusing on pathogenetic mechanisms that may play a role in diagnosis, management, and therapy of these complications. PMID- 11762997 TI - Pathogenesis of HIV-related pulmonary hypertension. AB - Human immunodeficiency virus (HIV)-related pulmonary hypertension (HRPR) is a cardiovascular complication of HIV infection that has been recognized in the last years with increasing frequency. The etiology of HRPH is unknown. All the attempts to isolate HIV on pulmonary vessels in HRPH patients failed, and an indirect role for HIV in this disease has been hypothesized. Current theories on the pathogenesis focus on abnormalities of endothelial and smooth muscle cells of pulmonary vasculature. Endothelial and smooth muscle cell injury could be due to a high production or to a reduced clearance of cytokines in these patients. In fact, in several studies high levels of ET-1, IL-1alpha, IL-6 and PDGF in primary pulmonary hypertension (PPH) and in HRPH have been found. HIV gp 120 could induce the production of these cytokines by a stimulation of monocytes/macrophages. A high alpha1-adrenoreceptors stimulation of pulmonary vessels could be also implicated in the pathogenesis of HRPH. Chronic hypoxia is observed with increased frequency in HIV patients, and this could induce a chronic stimulation of alpha1-receptors of pulmonary vasculature with typical pathological changes. However, only a small percentage of HIV- patients develop HRPH. This observation suggests the existence of an idiosyncratic susceptibility to the development of vascular disease. This susceptibility could have a genetic basis, and might be determined by particular major histocompatibility complex alleles. PMID- 11762998 TI - Cell death in HIV pathogenesis and its modulation by retinoids. AB - Patients infected with the human immunodeficiency virus exhibit a progressive decline in the CD4 T-cell number, resulting in immunodeficiency and increased susceptibility to opportunistic infections and malignancies. Although CD4 T cell production is impaired in patients infected with HIV, there is now increasing evidence that the primary basis of T cell depletion is accelerated apoptosis of CD4 and CD8 T cells. The rate of lymphocyte apoptosis in HIV infection correlates inversely with the progression of the disease: it is low in long-term progressors and in patients undergoing highly active antiretroviral therapy. Interestingly, only a minor fraction of apoptotic lymphocytes are infected by HIV, indicating that the enhanced apoptosis does not necessarily always serve to remove the HIV+ cells and results from mechanisms other than direct infection. Thus, understanding and influencing the mechanisms of HIV-associated lymphocyte apoptosis may lead to new therapies for HIV disease. In this paper the potential effects of retinoids on CD4 T cell apoptosis is discussed. PMID- 11762999 TI - Regulatory issues in Europe. PMID- 11763000 TI - The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. AB - In this study, the authors investigated the relationship between the metabolism of clomipramine (C) and the genotypes of cytochrome P450 (CYP) CYP2C19 and CYP2D6. Fifty-one Japanese patients (18 men and 33 women) were administered 10 to 250 mg/day of C by mouth and maintained on the same daily dose of C for at least 2 weeks to obtain steady-state concentrations. Plasma levels of C and its metabolites N-desmethylclomipramine (DC), 8-hydroxyclomipramine, and 8-hydroxy-N desmethylclomipramine (HDC) were determined by high-performance liquid chromatography. The allele frequencies of CYP2C19*2, CYP2C19*3, CYP2D6*5, and CYP2D6*10 were 27.5%, 12.8%, 2.9%, and 43.1%, respectively. Subjects who were homozygous for mutated alleles of CYP2C19 showed approximately 75% higher concentrations of C corrected by dose and body weight compared with those who were homozygous for wild-type alleles. Also, subjects who were homozygous for mutated alleles of CYP2C19 showed an approximately 68% higher value of C/DC compared with those who were homozygous for wild-type alleles. No significant difference in the ratio of DC/HDC was observed between subjects who were homozygous for mutated alleles of CYP2D6 and those who were homozygous for wild type alleles. These results suggest that genotyping CYP2C19 is useful for grossly predicting the risk of getting high plasma concentrations of C and the low individual capacity to demethylate C because there is marked interindividual variability within each genotype. However, the genotyping of CYP2D6 is not useful for predicting the individual capacity to hydroxylate DC. PMID- 11763001 TI - SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram. AB - Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it. PMID- 11763002 TI - The double-blind variable placebo lead-in period: results from two antidepressant clinical trials. AB - The 1-week single-blind placebo lead-in has long been a standard in double-blind psychopharmacology clinical trials. Although a lead-in period is often necessary (e.g., to receive laboratory results before randomization), some authors have demonstrated that the standard single-blind placebo lead-in's performance was similar to having a lead-in in which placebo was not administered. The single blind placebo lead-in did not decrease postrandomization placebo response, nor did it increase drug-placebo differences. To eliminate a higher percentage of placebo responders before randomization and to reduce potential biases in baseline ratings, the authors designed and implemented two depression studies with a double-blind variable placebo lead-in period. In these designs, both the patients and personnel at the investigative sites were blinded to the length of the placebo lead-in period and the start of the active treatment period. Approximately 28% of the patients in the double-blind placebo lead-in studies met criteria to be placebo lead-in responders, as compared with fewer than 10% from two single-blind placebo lead-in studies conducted in a similar time frame. Although all patients continued in the study (including placebo lead-in responders), the primary efficacy analysis prospectively excluded double-blind placebo lead-in responders. Analysis of postrandomization changes revealed that double-blind placebo lead-in responders, even when continuing to receive placebo treatment, maintained their response. At the study endpoint, these placebo lead in responders had significantly lower severity scores than their counterparts who were not lead-in responders. The prospective removal of lead-in responders thus resulted in an increase in mean endpoint placebo group severity scores. This resulted in an increased drug-placebo treatment difference in one of the two studies but had no effect on the treatment difference in the other study. PMID- 11763003 TI - Individual changes in clozapine levels after smoking cessation: results and a predictive model. AB - Published reports document 20-40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml +/- 598.8 ng/ml) occurred upon smoking cessation (p < .034) from a baseline level of 550.2 ng/ml (+/- 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (+/- 105.2 ng/ml) for the remaining cases (p < .001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F = 34.9;p = .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events. PMID- 11763004 TI - The effect of olanzapine treatment on m-chlorophenylpiperazine-induced hormone release in schizophrenia. AB - In addition to dopamine, serotonin (5-hydroxytryptamine, 5-HT) has been reported to play an important role in schizophrenia. Besides blocking dopamine, atypical antipsychotics also block 5-HT receptors. The clinical efficacy of the atypical antipsychotic clozapine is associated with the 5-HT antagonistic action of the drug and a high serotonergic tone before treatment. The atypical antipsychotic olanzapine has a receptor-binding profile similar to that of clozapine. The present study investigated whether treatment with olanzapine blocks hormone release induced by the 5-HT2c agonist m-chlorophenylpiperazine (m-CPP) and, if so, whether this 5-HT antagonistic effect is related to treatment response. Eighteen male schizophrenic patients participated in this study. All patients were challenged with m-CPP (0.5 mg/kg orally) in a double-blind, randomized, placebo-controlled design after a drug-free period of at least 2 weeks. Adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels were measured every 30 minutes up to 210 minutes after challenge. Patients were treated for 6 weeks with 10 mg olanzapine daily in an open design, after which the challenge tests were repeated. Olanzapine significantly blocked m-CPP-induced ACTH, cortisol, and prolactin release, suggesting that it is a potent 5-HT2c antagonist in vivo. This 5-HT antagonistic effect of olanzapine was not significantly correlated with treatment response. Also, no significant correlation was found between m-CPP-induced hormone release before treatment and clinical response after treatment with olanzapine. These findings suggest that olanzapine is a potent 5-HT2c antagonist in vivo but that this is unrelated to its clinical efficacy in this nonrefractory sample of schizophrenic patients. PMID- 11763005 TI - The efficacy and safety of risperidone for the treatment of geriatric psychosis. AB - Risperidone is an atypical antipsychotic drug which has been suggested to be beneficial for the treatment of elderly patients with psychotic symptoms. In this study, we assessed the short-term efficacy and the safety of risperidone in geropsychiatric inpatients with psychotic symptoms. The sample population included 110 elderly inpatients with psychotic disorders. Assessment for drug efficacy using the Brief Psychiatric Rating Scale, Sandoz Clinical Assessment Geriatric scale, and Clinical Global Impression scale was conducted at baseline and also at 4 weeks subsequent to risperidone treatment commencement. Subsequent to commencing risperidone treatment, 80 patients completed a 4-week therapeutic evaluation. Seventy (87.5%) of the 80 patients experienced mild to substantial improvement using the Clinical Global Impression scale. Adverse effects were monitored in all 110 patients. The most commonly detected adverse effects were weakness of legs or walking problems (43/110; 39.1%) and dizziness (32/110; 29.1%). Peripheral edema was noted in 18 (16.4%) patients. Risperidone, in low doses, appeared to have been effective in this sample of patients older than 65 years with psychotic symptoms. The mean dose (2.1 +/- SD 1.4 mg/day) applied was lower then that suggested for young patients and was related to the each specific patient diagnosis. Peripheral edema and walking problems were commonly observed adverse effects for these elderly patients, such problems having not been seen to the same extent in previous studies of young patients. PMID- 11763006 TI - Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients. AB - Nonlinear mixed effects modeling was used to estimate the effects of clonazepam carbamazepine interaction on clearance values using 359 serum levels gathered from 183 pediatric and adult epileptic patients (age range, 0.3-26.8 years) during their clinical routine care. Patients received the administration of clonazepam and/or carbamazepine. The final model describing clonazepam clearance was CL = 179.0 x TBW(-0.231) x 1.22(CBZ), where CL is total body clearance (mL/kg/h) and TBW is total body weight (kg); CBZ = 1 for concomitant administration of carbamazepine and CBZ = zero otherwise. The final model describing carbamazepine clearance was CL = 92.7 x TBW(-0.394) x DOSE(0-397) x 0.795(CZP), where DOSE is the daily dose of carbamazepine (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance and a 20.5% decrease in carbamazepine clearance. PMID- 11763007 TI - Ten-year follow-up of thyroid function in lithium patients. AB - The objective of this paper was to study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. Patients (N = 150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for the presence of thyroid autoimmunity, hypothyroidism, and goiter during a further period of lithium exposure of up to ten years. The following annual rates of newly developed thyroid dysfunction were observed: autoimmunnity (1.4%), subclinical hypothyroidism (1.7%), and goiter (2.1%). Subjects with thyroid autoimmunity had a higher chance of requiring substitution treatment with levothyroxine for subclinical hypothyroidism compared with subjects with no evidence of thyroid autoimmunity (13/32 = 41% versus 7/118 = 6%). Subjects (N = 15) who were prescribed carbamazepine in addition to lithium showed a significant decrease of TSH concentrations. In patients already being treated with lithium for several years, the overall incidence of hypothyroidism, goiter, and thyroid autoimmunity were comparable with those reported for the general population. However, lithium exposure may represent an additional risk factor for hypothyroidism in women and/or in the presence of thyroid autoimmunity. PMID- 11763008 TI - The H1-receptor antagonist dextro-chlorpheniramine impairs selective auditory attention in the absence of subjective awareness of this impairment. AB - Although previous studies have shown that the human attention system is partially affected by chlorpheniramine, the effects of chlorpheniramine on human auditory selective attention have not yet been explored. This study examines the effects of a single dose of 4 mg of dextro-chlorpheniramine on human auditory selective attention by means of the evaluation of the event-related brain potential (ERP) processing negativity (PN). The study sample consisted of 20 healthy male humans, who received either a single 4-mg dose of dextro-chlorpheniramine or a placebo in a double-blind design. The subjects were given a dichotic listening task, in which they were instructed to press a response button upon detecting deviant tones (target) while their ERPs were recorded. In parallel, subjective tests evaluated the daytime sleepiness, overall vigor, and affect of the subjects. Results showed that the auditory selective attention is impaired under the effects of chlorpheniramine, as reflected by an attenuation of PN amplitude and by a decrease of performance in the group of subjects who took a single 4-mg dose of dextro-chlorpheniramine. No subjective change in the daytime sleepiness, overall vigor, or affect of the subjects was observed. This lack of conscious awareness of the side effects may lead to situations of risk in tasks for which auditory information is important, because no subjective indicators of attention impairment are available to the subjects. PMID- 11763009 TI - Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C-->A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. AB - Antipsychotic response to clozapine varies markedly among patients with schizophrenia. The disposition of clozapine is dependent, in part, on the cytochrome P-450 (CYP) 1A2 enzyme in vivo. In theory, a very high CYP1A2 activity may lead to subtherapeutic concentrations and treatment resistance to clozapine. This prospective case study evaluates the clinical significance of ultrarapid CYP1A2 activity and a recently discovered single nucleotide (C --> A) polymorphism in intron 1 of the CYP1A2 gene (CYP1A2*F) for treatment resistance to clozapine. In addition, we describe the effect of grapefruit juice or low-dose fluvoxamine (25-50 mg/d) coadministration on clozapine and active metabolite norclozapine steady-state plasma concentration and antipsychotic response. PMID- 11763010 TI - Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study. AB - The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4 muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor. PMID- 11763011 TI - Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study. AB - The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity. PMID- 11763012 TI - Fluoxetine and norfluoxetine plasma levels after discontinuing fluoxetine therapy. PMID- 11763013 TI - A probable interaction between a very low-dose oral contraceptive and the antidepressant nefazodone: a case report. PMID- 11763014 TI - Abnormalities of thermoregulation induced by fluvoxamine. PMID- 11763015 TI - Therapeutic efficacy of allopurinol in mania associated with hyperuricemia. PMID- 11763016 TI - Gabapentin-related dyskinesia. PMID- 11763017 TI - Dopamine in catatonia. PMID- 11763018 TI - Differences between in vitro and in vivo determinations of fluvoxamine-clozapine interaction. PMID- 11763019 TI - Intranasal administration of delta sleep-inducing peptide increases P300. PMID- 11763020 TI - Differences in haloperidol epidemiologic pharmacokinetic studies. PMID- 11763021 TI - Clozapine and sudden death. PMID- 11763022 TI - A preliminary report on possible naltrexone and nonsteroidal analgesic interactions. PMID- 11763023 TI - Antidepressant effects of the herb Salvia divinorum: a case report. PMID- 11763024 TI - St. John's wort in generalized anxiety disorder: three case reports. PMID- 11763025 TI - Photochemical processes for atrazine degradation: methodological approach. AB - Numerous studies have been carried out on s-triazines, and more specifically on atrazine, with the long-term objective of resolving the problems caused by these herbicides: removing them from drinking water. However, applications have remained too limited. So far, processes based on photochemical degradation have been little implemented. We, therefore, investigated the development of photochemical processes, emphasizing their capacity to degrade triazine by photolytic and photocatalytic mode. The study sought to assess the performance of these ssstems. Experiments ts showed that according to a medium pressure mercury source (UV-Vis irradiation), the photolytic degradation of atrazine was very efficient, with a best atrazine degradation half-life shorter that 5 min. The main degradation pathway was deshalogenation. The photocatalytic degradation of atrazine under irradiation over 290 nm in the presence of titanium dioxide was shown to be efficient too, with a half-life of about 20 min. In this case an experimental design was conducted so as to assess the influence of various parameters: pH, water medium, and amount of catalyst. There has been observational evidence for the efficiency of the processes investigated here and for potential technological developments as regards drinking water treatment. PMID- 11763026 TI - Performance of stochastic approaches for forecasting river water quality. AB - This study analysed water quality data collected from the river Ganges in India from 1981 to 1990 for forecasting using stochastic models. Initially the box and whisker plots and Kendall's tau test were used to identify the trends during the study period. For detecting the possible intervention in the data the time series plots and cusum charts were used. The three approaches of stochastic modelling which account for the effect of seasonality in different ways. i.e. multiplicative autoregressive integrated moving average (ARIMA) model. deseasonalised model and Thomas-Fiering model were used to model the observed pattern in water quality. The multiplicative ARIMA model having both nonseasonal and seasonal components were, in general, identified as appropriate models. In the deseasonalised modelling approach, the lower order ARIMA models were found appropriate for the stochastic component. The set of Thomas-Fiering models were formed for each month for all water quality parameters. These models were then used to forecast the future values. The error estimates of forecasts from the three approaches were compared to identify the most suitable approach for the reliable forecast. The deseasonalised modelling approach was recommended for forecasting of water quality parameters of a river. PMID- 11763027 TI - Pre-acidification in anaerobic sludge bed process treating brewery wastewater. AB - The effect of pre-acidification on anaerobic granule bed processes treating brewery wastewater was the focus of a comparison study employing two configurations, (a) a single stage upflow anaerobic sludge bed (UASB) and (b) an upflow acidification reactor in series with a methanogenic UASB. The pre acidification reactor achieved 20 +/- 4% SCOD removal and 0.08 +/- 0.003 L of methane produced per gram of SCOD removal at a hydraulic retention time (HRT) of 0.75-4 h. Butyric acid was not detected and short chain fatty acids (SCFAs) were mainly acetic and propionic acids. The acidification ratio was about 0.42 +/- 0.02g SCFAs as COD,g of influent COD. Both systems' critical loading rate to achieve 80% COD removal was established at 34-39kgCOD/nm3 of total sludge bed volume per day. SCOD removal efficiency of 90 +/- 3% was achieved by both systems at an organic loading rate of 25 +/- 1 kg COD/m3 of total sludge bed volume per day, indicating that the installation of an acidification reactor had no effect in terms of the maximum granular activity, biomass granulation and the settleability of granules. At an organic loading rate of 67 kg COD/m3 of total sludge bed volume per day at an HRT of 1 h, the series system outperformed the single UASB by a removal of 62 compared to 57%. PMID- 11763028 TI - Optimization of activated sludge reactor configuration: kinetic considerations. AB - To evaluate and design staged activated sludge systems it is necessary to determine the biomass requirement for a given configuration. This depends on both kinetics and treatment requirements. We present a procedure to determine the optimum reactor configuration for a range of influent and effluent substrate concentrations, half saturation coefficients, and number of tanks in series for both inhibitory and non-inhibitory substrates. Dimensionless plots of the results show the minimum biomass requirement of the series relative to that for a single CSTR and the optimal relative sizes of the tanks. The plots may be used directly for staged system design and lead to the following conclusions: three tanks in series is generally best, high influent substrate concentrations and stringent discharge requirements increase the benefit of staging, and optimal tank sizing is significantly better than using equal sized tanks. PMID- 11763029 TI - A reappraisal of saprobic values and indicator weights based on Slovenian river quality data. AB - The saprobic values and indicator weights used in the Slovenian saprobic system are reappraised using data from the 1990 to 95 river quality surveys of Slovenia. The conceptual basis of the reappraisal is described and then formulated mathematically. The analysis is based on 1,106 biological samples and covers 300 taxa. The results are expressed in terms of revised saprobic values and indicator weights that mirror the ones previously assigned by ecological experts. The most significant differences between original and revised values are highlighted and discussed. It is concluded that: (a) the revised values and weights are more representative of their 'true' values than are the original values and weights, but that it would be premature to consider them definitive; (b) the analytical method provides a sound data-based approach to the revision of saprobic values and indicator weights; and (c) the method could help to improve and harmonise the various saprobic systems currently in use across Europe. PMID- 11763030 TI - Effect of bromide ions on genotoxicity of halogenated by-products from chlorination of humic acid in water. AB - Genotoxicity of halogenated by-products obtained by chlorination of humic acid in water was evaluated in the presence of bromide ions (Br-). After the halogenated humic acid solution was made to flow through CSP800 cartridge, absorbed substances were eluted with dimethyl sulfoxide or acetone, and subjected to mutagenicity assays and to analysis of trihalomethanes (THMs). Mutagenic activity was measured by Ames tests using S. typhimurium TA100 strain without metabolic activation, and by the frequencies of micronuclei formation using cultured Chinese hamster lung cells (CHL/IU) in vitro. A powerful effect of bromide ions in chlorinated humic acid solutions was observed on the reverse mutation and micronuclei formations. The formations of total THMs and more brominated THMs were also enhanced in the presence of bromide ions. The ratio of [Br-/Cl-] regulated the composition and concentrations of THMs intensely, and the rate of substitution of Br- was greater than that of chloride ions (Cl-). The increments of the mutagenicity and total THMs formed in chlorinated solutions were observed in parallel with the concentration of Br- or Cl-. From the observations, it was concluded that the increasing mutagenicity might be caused by the increasing chlorinated and/or brominated by-products. PMID- 11763031 TI - Effect of dissolved organic material and cations on freeze-thaw conditioning of activated and alum sludges. AB - Freeze-thaw conditioning effectively dewaters alum and activated sludges, but it works better on alum sludge than it does on activated sludge. The main difference between alum sludge and activated sludge is that activated sludge has high concentrations of both dissolved organic material and ions. Dissolved organic material and ions may possibly alter the freezing process and decrease the effectiveness of freeze-thaw conditioning on activated sludge. The objective of this study is to investigate the effect of dissolved organic material and cations on freeze-thaw conditioning of sludges, and to improve the effectiveness of freeze-thaw conditioning on activated sludge. The results of this study show that although protein, carbohydrate and cation concentrations in activated sludge supernatant are initially high, they dramatically increase after freeze-thaw conditioning. The increase is likely to come from the release of extracellular and intracellular material to sludge supernatant. The observed increase in the DNA concentration in activated sludge supernatant after freeze-thaw conditioning indicates that freeze-thaw causes cell disruption. Alum sludge supernatant, on the other hand, initially contains low concentrations of proteins, carbohydrates and cations which do not noticeably change after freeze-thaw conditioning. When ECPs (extracellular polymers) and cations are extracted from activated sludge before freeze-thaw conditioning. the sludge settles and dewaters better after the freeze-thaw. The resulting aggregates are smaller and denser resembling the "coffee ground" aggregates of alum sludge. PMID- 11763032 TI - Modelling the sewage discharge and dispersion of Cryptosporidium and Giardia in surface water. AB - Modelling the discharge of parasitic protozoa into surface water and the dispersion in rivers and streams gives insight into the contribution of the different sources of environmental contamination and in the transmission of these organisms from the point of discharge to drinking water abstraction points and bathing sites. We tested the applicability of emission (PROMISE) and dispersion (WATNAT) models developed for chemical pollutants to describe the environmental behaviour of Cryptosporidium and Giardia in the Netherlands. The annual load of Cryptosporidium and Giardia in domestic wastewater was 3.2 x 10(13) and 3.8 x 10(14) respectively. The majority (85%) of the Cryptosporidium oocysts was discharged with effluent of wastewater treatment plants. while the majority (82%) of the Giardia cysts was discharged with untreated wastewater discharges and sewer overflows. The estimated annual import through the river Rhine and Meuse was 3.2 x 1014 Cryptosporidium oocysts and 2.1 x 10(15) Giardia cysts, of which the river Rhine contributed 87 and 66%, respectively. This outweighed the total load of the discharges of treated and untreated wastewater in the Netherlands. The combination of PROMISE and WATNAT predicted concentrations of Cryptosporidium and Giardia in surface water that were in the same order of magnitude as the concentrations that were observed at 5 of the 6 sites compared. At a site with primarily agricultural contamination, the models predicted concentrations that were 1 10log-unit lower than the observed concentrations. This is a first step in the direction of a quantitative description of the transmission cycle of Cryptosporidum and Giardia through water. The use of these models combines observational occurrence data and experimental data from laboratory survival studies into a single integrated description. The description needs further improvement by incorporation of agricultural run-off and increasing the number and time frame of input monitoring data. PMID- 11763033 TI - Acid-stimulated phosphate uptake by activated sludge microorganisms under aerobic laboratory conditions. AB - Activated sludge inocula taken from five different wastewater treatment plants were grown aerobically under laboratory conditions on mineral salts medium containing either glucose or skimmed milk powder as carbon source. Cultures showed increases of between 50% and 143% in levels of phosphate uptake from the medium when the growth pH was 5.5 rather than 7.5. Of 100 individual sludge microbial isolates studied, 34 demonstrated such acid-stimulated luxury phosphate uptake; the optimum pH for the process was shown to lie between 5.0 and 6.5. Enhanced phosphate removal by these isolates was accompanied by increases of between 2 and 10.5-fold in their polyphosphate content; this was visualised as intracellular inclusions. Acid-stimulated luxury phosphate uptake by environmental microorganisms is a previously-unrecognised phenomenon that may have application in novel technologies for nutrient removal from wastewaters. PMID- 11763034 TI - Degradation of aroclor 1242 in a single-stage coupled anaerobic/aerobic bioreactor. AB - Degradation of Aroclor 1242 was studied in granular biofilm reactors with limited aeration. An aerobic biphenyl degrader, Rhodococcus sp. M5, was used to supplement a natural bacterial population present in a "bioaugmented" reactor, while the "non-bioaugmented" reactor only contained natural granular sludge. The bioaugmentation, however appeared to have no effect on the reactor performance. Aroclor measurements showed its disappearance in both reactors with only 16-19% of Aroclor recovered from the reactor biomass and effluent. Simultaneously, a chlorine balance indicated that dechlorination occurred at a specific rate of 1.43 mg PCB (g volatile suspended solids)(-1) d(-1), which was comparable to the observed rate of Aroclor disappearance. Intermediates detected in both reactors were biphenyl, benzoic acid, and mono-hydroxybiphenyls. This suggests that a near complete mineralization of Aroclor can be achieved in a single-stage anaerobic/aerobic system due to a combination of reductive and oxidative degradation mechanisms. PMID- 11763035 TI - Residue characteristics and pore development of petrochemical industry sludge pyrolysis. AB - Petrochemical industry bio-sludge was pyrolyzed to investigate the composition and pore size distribution of pyrolytic residue. Results indicated that the carbon, nitrogen, and hydrogen concentrations could be reduced after an increase in pyrolytic temperature. The trace element analysis indicated that Al, Ca, Fe, Mg. K, Cu, Sr, and Sb concentrated during the pyrolytic process. When forty grams of pre-dried sludge were pyrolyzed at various pyrolytic temperatures, the transfers from the gas phase to liquid phase to residue were from 21.2 to 36.0%, from 49.0 to 70.0%, and from 8.3 to 16.5%. Results of the pore size distribution examination indicated that the mesopore had the greatest effect on the bio-sludge pyrolysis. The optimal pyrolytic temperatures and times were approximately 800 degrees C for 30 min and 900 degrees C for 10 min. The conceptual model can reasonably explain the pore structure development during the pyrolysis process. PMID- 11763036 TI - Sequential inactivation of Cryptosporidium parvum using ozone and chlorine. AB - Inactivation of bovine-derived C. parvum oocysts was studied at bench-scale in oxidant demand free 0.05 M phosphate buffer using free chlorine alone or ozone followed by free chlorine at temperatures of 1 degrees C, 10 degrees C and 22 degrees C at pH 6. Animal infectivity using neonatal CD-1 mice was used for evaluation of oocyst viability after treatment. Kinetic models based on the linear Chick-Watson model were developed for free chlorine inactivation and ozone/free chlorine sequential inactivation for 0.4 or 1.6 log-units of ozone primary kill. At 22 degrees C. ozone pre-treatment increased the efficacy of free chlorine for about 4-6 times depending on the level of ozone primary kills. Gross kills of the ozone/free chlorine sequential inactivation were a function of ozone primary kills and increased linearly with the free chlorine C(avg)t (arithmetic average of the initial and final residual x contact time) product. Temperature was critical for both single and sequential inactivation, and the efficacy of free chlorine after 1.6 log-units of ozone primary inactivation decreased by a factor of 1.8 for every 10 degrees C temperature decrease. Given an ozone primary kill of 1.6 log-units, the free chlorine C(avg)t products required for a gross kill of 3.0 log-units were 1000, 2000 and 3,300 mgmin/L for 22 degrees C. 10 degrees C and 1degrees C, respectively. PMID- 11763037 TI - Analysis of microfiltration performance with constant flux processing of secondary effluent. AB - This study involves the microfiltration (MF) of secondary effluent from a sequencing batch reactor processing industrial waste. The MF unit was a hollow fibre module with gas backwash capability, and operated with pumped permeate (controlled flux) and dead-end, crossflow or intermittent feed. The results showed that crossflow had no effect on flux and that intermittent dead-end filtration was less productive than non-intermittent operation. For dead-end filtration the cycle-time between gas backwashes depends very significantly on the imposed flux (varying from about 100 min at 30 L/m2 h to about 5 min at 90 L, m2 h) and the feed solids content. Optimal operation has to balance operating (energy for backwash) costs and the capital (membrane area) costs. Cost analysis based on capital and energy costs indicates that for lower energy cost the unit needs to be operated at lower imposed flux but to minimise total cost it is necessary to operate the unit above 60 L/m2 h imposed flux depending on the maximum transmembrane pressure (TMP) allowed before back washing. Further analysis of TMP profiles showed that membrane resistance increased over time towards a maximum, which tended to increase with imposed flux. This implies more frequent chemical cleaning for high flux operation. Specific cake resistances were deduced from the profiles and indicated cake compression at higher flux and larger maximum TMP. Results of long-term trials are also reported. Water quality analysis shows consistent quality of permeate PMID- 11763038 TI - Transport and fate of Cryptosporidium parvum oocysts in intermittent sand filters. AB - The transport potential of Cryptosporidiim parvum (C. parvum) through intermittent. unsaturated, sand filters used for water and wastewater treatment was investigated using a duplicated. 2(3) factorial design experiment performed in bench-scale, sand columns. Sixteen columns (dia = 15 cm, L = 61 cm) were dosed eight times daily for up to 61 days with 65,000 C. parvum oocysts per liter at 15 degrees C. The effects of water quality, media grain size, and hydraulic loading rates were examined. Effluent samples were tested for pH, turbidity, and oocyst content. C. parvum effluent concentrations were determined by staining oocysts on polycarbonate filters and enumerating using epifluorescent microscopy. At completion, the columns were dismantled and sand samples were taken at discrete depths within the columns. These samples were washed in a surfactant solution and the oocysts were enumerated using immunomagnetic separation techniques. The fine grained sand columns (d50 = 0.31 mm) effectively removed oocysts under the variety of conditions examined with low concentrations of oocysts infrequently detected in the effluent. Coarse-grained media columns (d = 1.40 mm) yielded larger numbers of oocysts which were commonly observed in the effluent regardless of operating conditions. Factorial design analysis indicated that grain size was the variable which most affected the oocyst effluent concentrations in these intermittent filters. Loading rate had a significant effect when coarse-grained media was used and lesser effect with fine-grained media while the effect of feed composition was inconclusive. No correlations between turbidity, pH, and effluent oocyst concentrations were found. Pore-sizc calculations indicated that adequate space for oocyst transport existed in the filters. It was therefore concluded that processes other than physical straining mechanisms are mainly responsible for the removal of C. pavum oocysts from aqueous fluids in intermittent sand filters used under the conditions Studied in this research. PMID- 11763040 TI - The influence of salting out on the sorption of neutral organic compounds in estuaries. AB - The relative (unsaturated) solubility and sorption of 2,2',5,5' tetrachlorobiphenyl have been studied along an estuarine salinity gradient. The aqueous compound was salted out with increasing salinity and an aqueous salting constant of about 0.0021 g(-1) was derived. Sorption of the compound to estuarine particles increased with increasing salinity for a range of particle concentrations, but the magnitude of this effect (sorption salting constants of about 0.005-0.011 g(-1)) indicated that salting out of the aqueous phase was not solely responsible. It is suggested that the hydrophobicity of sediment organic matter is enhanced by its interaction with seawater ions through a reduction in the charge of the particle surface and, possibly, modification of the structure of the organic matter. Examination of literature data on the sorption of neutral organic compounds to estuarine sediment indicates a general increase in sorption with increasing salinity which can be empirically defined by a salting equation. Although charge reduction of estuarine particles is a general observation, it is not possible to establish the general significance of this effect (or any other form of salting out of sediment organic matter) on the sorption of organic compounds in estuaries because appropriate site- and compound-specific aqueous salting constants are unavailable. Increased sorption at high salinities has obvious implications for the disposal and transport of organic chemicals in estuaries. However, the inverse dependency of sediment-water partitioning on particle concentration is likely to be of at least equal significance in macrotidal environments where sediment resuspension occurs. An empirical model, combining the effects of salinity and particle concentration, is proposed for deriving first-order estimates of the partitioning of neutral organic compounds in estuaries. PMID- 11763039 TI - Sonochemical decomposition of dibenzothiophene in aqueous solution. AB - Dibenzothiophene is decomposed rapidly by sonication in aqueous solution. Decomposition of dibenzothiophene follows a first-order reaction kinetics. The rate constant was found to increase with increasing ultrasonic energy intensity, temperature, and pH and decrease with increasing initial dibenzothiophene concentration. The activation energy was 12.6 kJ mol in the temperature range of 15-50 degrees C, suggesting a diffusion-controlled reaction. Hydroxydibenzothiophenes and dihydroxydibenzothiophenes were identified as reaction intermediates. It is proposed that dibenzothiophene is oxidized by OH radical to hydroxy-dibenzothiophenes and then to dihydroxy-dibenzothiophenes. Kinetic analysis suggests that approximately 72% of the dibcnzothiophene decomposition occurred via OH radical addition. A pathway and a kinetic model for the sonochemical decomposition of dibenzothiophene in aqueous solution are proposed. PMID- 11763041 TI - Exploratory analysis of the effects of particulate characteristics on the variation in partitioning of nonpolar organic contaminants to marine sediments. AB - The partitioning of nonpolar organic contaminants to marine sediments is considered to be controlled by the amount of organic carbon present. However, several studies propose that other characteristics of sediments may affect the partitioning of contaminants. For this exploratory analysis, we measured 19 sediment characteristics from five marine sediments and 11 characteristics of humic acids extracted from the sediments. These characteristics included elemental composition, grain size, soot carbon, polarity indices and molar ratios. Each individual characteristic and combinations of these characteristics were then used to normalize partition coefficients (Kp) generated for three organic contaminants: lindane, fluoranthene and a tetrachlorinated biphenyl (PCB). A coefficient of variation (CV) was then calculated for each contaminant to determine which normalization characteristic (individually or in combination) resulted in the lowest variability in partitioning between study sediments. For lindane and the PCB. normalization by the amount of sediment organic carbon resulted in the lowest variability in partition coefficients with CVs of 16.2% and 37.7%. respectively. However, normalization of fluoranthene by silt content resulted in lower CVs than those generated by organic carbon normalization: 31.0% vs. 37.6%. Normalization of contaminants Kp's by combined values of sediment characteristics resulted in lower CVs but only by a few percent. Using humic acid characteristics, humic organic carbon reduced variability between sediments most effectively. But only the normalized fluoranthene values had a CV (i.e., 25.4%) lower than the one based on normalization by sediment characteristics. When combined, humic acid characteristics resulted in lower CVs than normalization by individual or combinations of sediment characteristics for fluoranthene and the PCB with CVs of 19.3% and 28.7%, respectively. This analysis indicates variability associated with the partitioning of some organic contaminants to marine sediments can be further reduced when normalization by sediment characteristics other than organic carbon are utilized. PMID- 11763042 TI - Removal of cadmium and manganese by a non-toxic strain of the freshwater cyanobacterium Gloeothece magna. AB - The ability of both living and dry cells of Gloeothece magna, a non-toxic freshwater cyanobacterium, to adsorb cadmium and manganese is demonstrated in this study. Chlorophyll a content of living cells was not influenced by either cadmium or manganese concentrations, indicating that adsorption of both Cd2+ and Mn2+ by living cells of G. magna, was independent of the metabolic state of the organism. Moreover, the adsorption of both Cd2+ and Mn2+ to living cells and dry cells, was dependent on the metal concentrations, and fitted the Freundlich adsorption isotherm. However, dry cells had larger binding capacity for both Cd2+ (Kf = 912.6) and Mn2+ (Kf = 2,398) than living cells (Kf = 151.4 & 63, respectively). The role of the capsular polysaccharides, the main constituents of the cyanobacterial envelope, in binding these two metals was also studied. Polysaccharide extracts of this organism adsorbed high amounts of both Cd2+ (I15 425 microgmg(-1)) and Mn2+ (473-906 microgmg(-1)). This study suggests that G. magna would probably be cultured in water bodies contaminated by heavy metals to ameliorate their toxicity. Also dry material of this cyanobacterium being a non toxic species, could be used as a safe biofilter to remove toxic metals from drinking water. PMID- 11763043 TI - Electrochemical treatment of acidic aqueous ferrous sulfate and copper sulfate as models for acid mine drainage. AB - Acid mine drainage (AMD) is a serious environmental problem in the mining industry. The present work describes electrolytic reduction of solutions of synthetic AMD, comprising FeSO4/H2SO4 and CuSO4/H2SO4, in flow-through cells whose anode and cathode compartments were separated using ion exchange membranes. In the case of FeSO4/H2SO4 at constant flow rate, the pH of the effluent from the catholyte increased progressively with current at a variety of cathodes, due to electrolytic reduction of H+ ions to elemental hydrogen. Near-quantitative removal of iron was achieved by sparging air into the catholyte effluent, thereby precipitating iron outside the electrochemical cell, and avoiding fouling of the electrodes. The anode reaction was the oxidation of water to O2, a proton releasing process. Using cation exchange membranes and sodium sulfate as the supporting electrolyte in the anode compartment, the efficiency of the process was compromised at high currents by transport of H+ competitively with Na+ from the anode to the cathode compartments. Higher efficiencies were obtained when anion exchange membranes were used, and in this case no additional supporting electrolyte other than dilute H2SO4 was needed, the net reaction being the electrochemically driven transfer of the elements of H2SO4 from the cathode to the anode compartments. Current efficiencies approximately 50% were achieved, the loss of efficiency being accounted for by ohmic heating of the solutions. In the case of CuSO4/H2SO4 and anion exchange membranes at high currents, reduction of Cu2+ and H+ ions and transport of SO4(2-) ions out of the catholyte caused unacceptably high potentials to be generated. PMID- 11763044 TI - Aerobic biological treatment of a pharmaceutical wastewater: effect of temperature on cod removal and bacterial community development. AB - The effect of temperature was studied on the efficiency of soluble COD removal and bacterial community development during the aerobic biological treatment of a pharmaceutical wastewater. Using wastewater and bacterial inoculum obtained from the full-scale facility treating this wastewater, batch laboratory cultures were operated at 5 degrees C intervals from 30 degrees C to 70 C. Following four culture transfers to allow for bacterial acclimation, residual soluble COD levels were measured and bacterial community fingerprints were obtained by denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments. Soluble COD removal efficiency declined as temperature increased from 30 degrees C (62%) to 60 degrees C (38%). Biological treatment of this wastewater failed to occur at temperatures higher than 60 C. Gradual shifts in bacterial community structure were detected as temperature increased, including a concomitant reduction in the number of different bacterial populations. The impact of temperature on a two-stage biological treatment process was also compared. Better soluble COD removal was achieved when both reactors were operated at 30 degrees C compared to a system where the two stages were consecutively operated at 55 degrees C and 30 degrees C. These results indicate that operation of aerobic biological wastewater treatment reactors at elevated temperatures can have adverse effects on process performance. PMID- 11763045 TI - Membrane and solution effects on solute rejection and productivity. AB - Limited understanding of the physical and chemical processes involved in membrane processes affects their widespread application in drinking water treatment. Insight into these processes was attained through a systematic manipulation of solution chemistry in membrane filtration with three 'loose' nanofiltration membranes. Eighteen known solutions were created varying pH, ionic strength, and major cation valence in the presence of a commercial humic acid. The membrances varied as well, including a non-ionic hydrophobic, a non-ionic hydrophilic, and an anionic hydrophilic membrane surface. Specific membrane productivity and TOC and conductivity rejection were monitored. In all cases, the presence of divalent cations decreased the rejection of both conductivity and organic matter. Divalent cations also greatly increased the rate of productivity decline over equivalent tests in solutions with monovalent cations. The most hydrophobic membrane had the greatest productivity decline rate under all solution conditions. The lowest ionic strength solutions showed the greatest TOC and conductivity rejection and the greatest rate of productivity decline for each of the membranes. PMID- 11763046 TI - Effects of natural organic matter, anthropogenic surfactants, and model quinones on the reduction of contaminants by zero-valent iron. AB - Recent studies of contaminant reduction by zero-valent iron metal (Fe0) have highlighted the role of iron oxides at the metal-water interface and the effect that sorption has at the oxide-water interface on contaminant reduction kinetics. The results suggest that a variety of organic surface-active substances might enhance or inhibit contaminant degradation, depending on the degree to which they promote solubilization, sorption. and/or reaction. Of particular interest is the effect of natural organic matter (NOM), because of its ubiquitous presence in natural waters and amphiphilic properties; anthropogenic surfactants, because of their use in groundwater remediation; and certain quinones, which represent the redox-active functional groups associated with NOM. In this study, no well defined effects of these substances were found on the reduction of nitro benzene by Fe0, but the reduction of carbon tetrachloride and trichloroethylene (TCE) was inhibited by NOM. Results with carbon tetrachloride showed that the inhibitory effect of humic acids was greater than fulvic acids, but that several quinonoid NOM model compounds (juglone, lawsone. and anthraquinone disulfonate) increased the rate of reduction by Fe0. Isotherms for adsorption of TCE and NOM onto Fe0 showed evidence of competition for surface sites. PMID- 11763047 TI - Assimilable organic carbon (AOC) and biodegradable dissolved organic carbon (BDOC): complementary measurements. AB - The objective of this study was to evaluate the necessity of measuring both assimilable organic carbon (AOC) and biodegradable dissolved organic carbon (BDOC) as indicators of bacterial regrowth potential. AOC and BDOC have often been measured separately as indicators of bacterial regrowth, or together as indicators of bacterial regrowth and disinfection by-product formation potential, respectively. However, this study proposes that both AOC and BDOC should be used as complementary measurements of bacterial regrowth potential. In monitoring of full-scale membrane filtration, it was determined that nanofiltration (NF) removed over 90% of the BDOC while allowing the majority of the AOC through. Heterotrophic plate counts (HPC) remained low during the entire period of monitoring due to high additions of disinfectant residual. In a two-year monitoring of a water treatment plant that switched its treatment process from chlorination to chlorination and ozonation, it was observed that the plant effluent AOC increased by 127% while BDOC increased by 49% after the introduction of ozone. Even though AOC is a fraction of BDOC, measuring only one of these parameters can potentially under- or overestimate the bacterial regrowth potential of the water. PMID- 11763048 TI - Influence of the characteristics of natural organic matter on the fouling of microfiltration membranes. AB - Natural organic matter (NOM) plays a significant role in fouling microfiltration membranes in drinking water treatment processes even though the NOM is retained only to a small extent. The aim of this study was to obtain a better understanding of the interactions between the fractional components of NOM and microfiltration membranes. Filtration experiments were performed using 0.22 microm hydrophobic and hydrophilic polyvinylidene fluoride (PVDF) membranes in a stirred-cell system on the NOM isolated from three Australian surface waters. As expected, the fouling rate for the hydrophobic membrane was considerably greater than for the hydrophilic membrane. Focusing on the hydrophobic membrane, it was shown that the high molecular weight fraction of NOM ( > 30 kDa) was responsible for the major flux decline. Filtration tests on the four fractions of NOM isolated on the basis of hydrophobicity and charge using non-functionalised and anionic resins revealed that the fouling potential for the three waters was hydrophilic neutral > hydrophobic acids > transphilic acids > hydrophilic charged. The low-aromatic hydrophilic neutral compounds were the main determinant of the rate and extent of flux decline. This was linked to the colloidal size fraction ( > 30 kDa) and to the selective concentration of calcium in the fraction leading to organics-Ca2+ bridging. It was also shown that the higher the aromaticity of the NOM the greater the flux decline, and the aromatics mainly resided in the hydrophobic acids fraction. Overall, the fouling mechanism controlling the flux decline involved the combined effects of adsorptive and colloidal fouling by the hydrophilic neutral fraction in the internal pore structure of the membrane. PMID- 11763049 TI - The impact of ferrous ion reduction of chlorite ion on drinking water process performance. AB - The use of chlorine dioxide (ClO2) as a primary disinfectant and pre-oxidant in drinking water treatment is being explored as an alternative to chlorine for reducing disinfection by-product formation and to assure compliance with United States Environmental Protection Agency's Stage 1 Disinfection/ Disinfection By Products Rule. However, the ClO2 by-product chlorite ion (ClO2-) is also regulated by the same regulation. Ferrous iron (Fe(II)) has been shown to effectively reduce chlorite ion to chloride ion (Cl-) and this study was conducted to evaluate the impact on overall treatment process performance due to the ferric hydroxide solids that form from the reaction. Ferrous iron application was explored at three different points in a pilot-scale water treatment system: pre-rapid mix. pre-settling and pre-filter. Chlorite ion concentrations were effectively reduced from 2mg/L to less than 0.3mg/L using an Fe(II) dose of approximately 6mg/L for all trials. Fe(II) addition at the rapid mix caused no adverse effects and, in fact, allowed for reduction of the alum dose due to the newly formed ferric hydroxide acting as a supplemental coagulant. An increase of 241 and 247% of total suspended solids influent to the filter process was observed when Fe(II) was applied at the pre-settling and pre-filter locations. Pilot-scale filter runs during these trials were less than 2 h and never obtained true steady state conditions. Jar testing was performed to better understand the nature of the ferric hydroxide solids that are formed when Fe(II) was oxidized to Fe(III) and to explore the effectiveness of Fe(II) addition at intermediate stages in the flocculation process. PMID- 11763051 TI - Expanding the scope of chemical vapor generation for noble and transition metals. AB - A modified Bergener parallel path nebulizer was used for the generation of volatile metal species of Pt, Co, Ag, Cu, Rh, Pd, Au, Ni, Ir, Ti and Mn through reaction with tetrahydroborate (III). Several physicochemical factors were identified which impact on their yield which, at present, is estimated to range from 0.02-2% absolute. PMID- 11763050 TI - Batch-mixed iron treatment of high arsenic waters. AB - This paper develops batch-mixed treatment with zero-valent iron as a point-of-use technology, appropriate for arsenic removal from water stored within rural homes in Bangladesh and West Bengal, India, where arsenic poisoning has affected an estimated 20 million people. Batch tests with iron yielded the following results: (1) High arsenic removal (>93%) was achieved from highly arsenated waters (2,000 microg/L) over short contact times (0.5-3h) with iron filings added at doses ranging from 2500 to 625 mg/L; (2) Most rapid arsenic removal was observed in head-space free systems with sulphates present in solution, while phosphate buffers were observed to inhibit arsenic removal by iron; (3) The arsenic removed from water was found to be strongly bound to the elemental iron filings, such that the treated water could be decanted and iron could be reused at least 100 times; (4) Some iron dissolved into water over the contact period, at concentrations ranging from 100 to 300 microg/L, which are within safe drinking water limits. These results indicate that, with appropriate assessment of water chemistry in the affected region, treatment with metallic iron followed by simple decantation can be used as a practical, in-home, point-of-use technique for reducing human exposure to arsenic in drinking water. PMID- 11763052 TI - Synchronization of separation and determination based on multichannel mode filtered light detection with capillary electrophoresis. AB - A novel method for the synchronization of separation and determination is described, in which a mode-filtered light detector is used as an online detector in capillary electrophoresis. An instrument is described which has been developed for this purpose. The round capillary used in conventional capillary electrophoresis is replaced by an annular column, which is constructed from a naked optical fibre inserted into a fused-silica capillary. In fact, the annular electrophoresis column itself forms part of the mode-filtered light sensor. Along the side of the annular column are several detection channels for gathering and transmitting the mode-filtered light to a charge-coupled device (CCD). Every channel provides information on the sample from the point at which it is located. Using capillary isotachophoresis incorporating the annular column, the analytes in a sample containing alanine (10.0 mM) and glycine (9.7 mM) were simultaneously separated and determined using multichannel mode-filtered light detection with a detection limit of 1.5 mM. PMID- 11763053 TI - Electrochemically modulated liquid chromatography: an electrochemical strategy for manipulating chromatographic retention. PMID- 11763054 TI - Disorganised self-assembled monolayers (SAMs): the incorporation of amphiphilic molecules. AB - A new approach for designing a voltammetric selective electrode is presented. The approach is based on the formation of a disorganised inert self-assembled monolayer (SAM), in which an amphiphilic molecule is incorporated. The latter serves as the selectivity factor, which extracts the analyte. The purpose of these experiments is to study the parameters that affect the capability of a monolayer to host amphiphiles. As model systems we focused on the incorporation of simple amphiphilic molecules (quaternary alkyl ammonium salts), electroactive amphiphiles (dialkylviologens) and a macrocycle ligand (tetramethylcyclam) into octadecyl silane monolayers formed on indium tin oxide (ITO) and purposely made disorganised alkanethiols on gold. We find that basically, the incorporation of amphiphiles into a hydrophobic inert SAM resembles a reversed stationary phase in liquid chromatography and this configuration can be used for designing selective electrodes. PMID- 11763055 TI - Zeolite-membrane modulation of simple and facilitated ion transfer. AB - The silicalite-modified water/organic interface represents a novel system, which is of potential utility for electroanalytical studies. As a means of investigating the analytical potential of this interface the facilitated transfer of various alkali and alkaline earth metal ions have been investigated using voltammetric methods. Additionally, the size selective transfer of tetraalkylammonium ions across this modified interface has been studied and a possible adsorption process that may be a step in the overall transfer has been identified. PMID- 11763056 TI - Stable sensor layers self-assembled onto surfaces using azobenzene-containing polyelectrolytes. AB - Polyelectrolytes functionalized with photoisomerizable azobenzene chromophores were multi-layered onto inorganic and metal surfaces, by the repeated adsorption from dilute aqueous solution, alternating between oppositely charged polymers. These layer-by-layer ionically self-assembled thin films were investigated for their suitability as sensor host materials with respect to the criteria of control over physical layer properties, versatility to different substrates and adsorption geometries, and stability of the formed layers to heat, solvent, and sonication. Layer thickness was found to be controllable between 5 A and 500 nm by varying the total number of layers deposited, from a single monolayer to 1000 layers. Control over individual layer thickness was achieved by varying the pH of the adsorption solutions. This multi-layer self-assembly was demonstrated to be suitable for a wide range of metal and inorganic substrates, and achievable with surfaces of high curvature (r = 50 nm), and confined geometry. The deposited layers exhibited good stability to desorption in a range of organic solvents, aqueous temperatures to 100 degrees C, and cleaning protocols such as sonication. The laser-induced geometric isomerization of the azobenzene chromophores was shown to be strongly dependent on aqueous solution properties, demonstrating an application as a hydroxide ion sensor in highly alkaline media. PMID- 11763057 TI - An assay for the enzyme N-acetyl-beta-D-glucosaminidase (NAGase) based on electrochemical detection using screen-printed carbon electrodes (SPCEs). AB - An electrochemical assay for the enzyme N-acetyl-beta-D-glucosaminidase (NAGase) is described, using bare screen-printed carbon electrodes (SPCEs). The enzyme substrate, 1-naphthyl-N-acetyl-beta-D-glucosaminide, was added to the NAGase containing sample under hydrodynamic conditions and was hydrolysed to 1-naphthol, which was monitored amperometrically at an Eapp of +650 mV versus SCE. A pH study revealed the apparent Vmax for the assay to occur at pH 4.5. corresponding to an apparent substrate Km of 0.28 mM. In order to be compatible with the analysis of biological fluids, a final operating pH of 5.4 was selected, and, using a data recording time of 100 s post-substrate addition, the assay gave a linear response (r2 = 0.988) over the range 3.1 to 108 mU ml(-1) NAGase (RSD = 15.4%). This assay has the potential to monitor NAGase levels in a number of application areas. PMID- 11763058 TI - Electrochemical and spectroscopic characterization of quinone functionalized exfoliated graphite. AB - Natural graphite was exfoliated by thermal decomposition of graphite-bisulfate intercalation compound. Oxidative/reductive pre-treatment of exfoliated graphite was subsequently carried out to introduce various functional groups on the graphite surface. The resulting material was covalently modified with redox active quinones. The covalent modification was effected through oxygen containing functional groups formed on the graphite surface. The modified exfoliated graphite was characterized by infra-red (FTIR) and X-ray photoelectron spectroscopy (XPS). Electrochemical characterization of the pressed pellets of the modified graphite showed that the modification occurred at the edge sites. These electrodes were found to be very stable and the surface renewal was simply accomplished by polishing the surface using SiC emery sheets. Application of the benzoquinone modified electrode for the electrocatalysis of ascorbic acid oxidation was demonstrated. PMID- 11763059 TI - Nanocomposite electrodes made of carbon nanofibers and black wax. Anodic stripping voltammetry of zinc and lead. AB - Nanocomposite electrodes offer exciting new possibilities in electroanalytical chemistry. In this preliminary study, nanocomposite electrodes made of carbon nanofibers and black wax were characterized and investigated as novel substrates for metal deposition and stripping processes. Carbon nanofibers were grown from ethylene-hydrogen gas mixtures over Fe-Ni-Cu (85:10:5) nanoparticle catalysts at 600 degrees C and then embedded in Apiezon black wax under vacuum at 140 degrees C. The resulting nanocomposite electrodes showed (i) good conductivity, (ii) a wide potential window in aqueous solutions, (iii) low background currents, (iv) near steady state voltammetric responses with substantial Faradaic currents and (v) sharply peaked fast scan metal stripping responses. Zinc is a notoriously difficult metal to determine in aqueous solutions, because its deposition and stripping are accompanied by hydrogen evolution at extreme negative potentials. It therefore provided a challenging test for our new nanocomposite electrode. Although numerous complications associated with the hydrogen evolution process could not be eliminated, remarkably clear voltammograms could be obtained even at scan rates of 40 V s(-1). PMID- 11763060 TI - Potentiometric titrations using dual microband electrodes. AB - We present a novel method of analysis using potentiometric end-point detection and dual microband electrodes in generator-collector mode. The titrant is electrogenerated using either a constant current or a current that increases linearly with time, and the fluxes of reactive material rather than molar amounts are balanced. The advantage of the ramp current system over the constant current method is that all of the information needed for a full titration curve and a proper analysis can be obtained during a single scan. The method was applied to the determination of vitamin C with ferricyanide and to the determination of thiosulfate and sulfite with iodine using gold microband electrodes. As a new type of analysis, a potentiometric titration that uses dissolving silver microband electrodes in order to generate the titrant is demonstrated. The system was applied to the detection of chloride, iodide, thiosulfate and cyanide. The accuracy of the analysis is +/-10%, limited mainly by the present screen-printing process, and the method is well adapted for measurements on the millimolar scale. PMID- 11763061 TI - Simulation of the microdisc problem in spherical co-ordinates. Application to electrochemiluminescence homogeneous analysis. AB - The chemical transformations of electrogenerated ion-radicals of a number of complex organic compounds may be accompanied by emission of photons. An electrogenerated chemiluminescence (ECL) quantum contains information both on the kinetics of the heterogeneous electrode processes and on the subsequent homogeneous chemical reactions in the solution. Application of ECL to solution analysis provides advantages in comparison to electrochemical methods. We demonstrate a new approach for numerical simulation of the microdisc problem in spherical co-ordinates and apply it to ECL homogeneous analysis under non-steady state electrolysis. PMID- 11763062 TI - Electrochemical recognition of charged species using quaternary ammonium binaphthyl salts. AB - The effects of ionic analytes on the electrochemical properties of quaternary ammonium binaphthyl salts are described in this work. The stability of the binaphthyl radicals and hence the reversibility of the electrochemical response are discussed in terms of molecular structure. The ability of azacrown derivatised binaphthyl salts to act as amperometric receptors is ascribed to the strain imparted in the cyclic ammonium ring when Li+ ions complex with them. It is also shown that the redox properties of quaternary ammonium binaphthyl salts are pH dependent in aqueous solutions, but that reversible redox properties can be observed in extremely basic solutions. The effect of anions binding to the quaternary ammonium cation can be seen in the redox properties of the binaphthyl moiety and the use of a chiral binding site for enantiomeric recognition is also demonstrated. PMID- 11763063 TI - Voltammetric investigation of hair dye constituents: application to the quantification of p-phenylenediamine. AB - The application of electrochemical techniques to the determination of common hair dye constituents was investigated. Cyclic voltammetry was used to probe the electrode response to p-phenylenediamine (PPD), 4-chlororesorcinol and m aminophenol with square wave voltammetry used to effect quantitative measurements. The nature of the electrode response was characterised and issues of surface fouling resulting from the deposition of electrogenerated reaction products were addressed. A procedure designed to allow the facile determination of PPD in hair care products is presented. PMID- 11763064 TI - Investigation of mechanisms for the reductive dechlorination of chlorinated ethylenes using electroanalytical techniques. AB - Chlorinated ethenes in the environment can dechlorinate by accepting electrons from electron donors fortuitously found in nature under a wide range of conditions in the sub-surface by both abiotic and biotic pathways. A source of electron donors is a range of dehalorespiratory bacteria, in which Co(I) in vitamin B12, in the presence of strong reductants such as Ti(III) citrate, aids dehalogenation. In this work we investigated a range of reducing conditions using electron donors of varying strengths and proposed mechanisms for dechlorination. Initially, the reducing abilities of one of the strongest electron donors known, tetrakis(dimethylamino)ethylene (TDAE), was studied. Subsequently, the reducing ability of a cobalt salt under reducing conditions was examined. Molasses was used as a source of hydrogen. The reactions were followed using electrochemistry, UV-Vis spectroscopy and ion chromatography. TDAE was found to form adducts with tetrachloroethylene and trans-dichloroethylene and to reduce trichloroethylene and cis-dichloroethylene very rapidly. On application of a negative potential, cobalt, in the presence of molasses, was also found to dechlorinate trichloroethylene rapidly. Dechlorination of PCE was considerably slower. PMID- 11763065 TI - Catalytic hydrogen evolution in cathodic stripping voltammetry on a mercury electrode in the presence of cobalt(II) ion and phenylthiourea or thiourea. AB - The system Co(II)-phenylthiourea (PTU)-borax buffer was investigated by cathodic stripping voltammetry (CSV) at a hanging mercury drop electrode. The results of the voltammetric measurements showed that the presence of both PTU and Co(II) gives rise to a new irreversible peak at about -1.5 V. Based upon our previous results obtained in the study of other sulfur compounds and the sulfide ion itself, the peak was ascribed to the catalytic hydrogen evolution superimposed on the reduction of the coordinated Co(II) ion. The catalyst itself is a Co(II) complex with the sulfide ion produced by the decomposition of the analyte during the deposition step. The influence of PTU and cobalt concentration, accumulation conditions and stripping parameters was investigated and complementary data on thiourea are included. The results showed that the measurement of the catalytic hydrogen evolution peak current can be used as a basis for a simple, accurate and rapid method for the determination of PTU within the concentration range 10-100 nM. The catalytic method is relatively free of interferences and could be a suitable alternative for cases in which the stripping peak due to mercury ion reduction in the accumulated mercury compound is disturbed by some interference. PMID- 11763066 TI - Redox modification of proteins using sequential-parallel electrochemistry in microtiter plates. AB - Redox modification of proteins has frequently been used to improve the electron transfer properties in amperometric biosensors. One approach is the coordinative labelling of histidine residues with metal complexes like [Ru(bpy)2Cl2] and [Ru(bpy)2CO3]. Although the reaction depends on a variety of parameters no detailed optimisation of these modification procedures has been done, most probably due to the complexity of the parameter matrix and the expected differences for any individual protein. A multi electrode sequential analyser (MESA) system has been developed which allows one to follow in a sequential parallel scheme a number of modification reactions by performing electrochemical measurements such as cyclic voltammetry or differential pulse voltammetry in individual wells of a conventional microtiter plate. Using this system, the ligand exchange reaction leading to the binding of the Ru-complex to histidine residues could be investigated with imidazole as a model compound. Furthermore, the selective labelling of soluble PQQ (pyrrolochinolinquinone)-dependent glucose dehydrogenase (sGDH) and glucose oxidase (GOx) with Ru complexes could be optimised and the electrochemical and biological properties of the obtained 'electroenzymes' were examined. PMID- 11763067 TI - A glucose biosensor based on electrodeposited biocomposites of gold nanoparticles and glucose oxidase enzyme. AB - Electrodeposition was used for the codeposition of glucose oxidase enzyme and a gold nanoparticle-silicate network onto an indium tin oxide (ITO) glass electrode. This co-entrapment of glucose oxidase enzyme in a gold nanoparticle silicate network imparts biocatalytic activity to the film. The gold nanoparticles in the network catalyse the oxidation and reduction of H2O2, the by product of the enzymatic reaction. The low operating potential of the sensor eliminates the interference from common interferents, such as acetaminophen, ascorbic acid, dopamine, etc. PMID- 11763068 TI - Two OPEEs (organic phase enzyme electrodes) used to check the percentage water content in hydrophobic foods and drugs. AB - The development and optimization of an analytical method using enzymatic biosensors able to operate in organic solvents [organic phase enzyme electrodes (OPEEs)] for the determination of the water content in food fats (butter, margarine) or pharmaceutical or cosmetic ointments is described. The method is based on the increase in enzymatic activity which is related to the increase in the percentage water content in the organic phase into which the biosensor is dipped. The enzymes used to assemble the biosensors were tyrosinase or catalase, the substrates were phenol or p-cresol and tert-butyl hydroperoxide, respectively, and the organic solvents were acetonitrile or dioxane. A gas diffusion amperometric electrode for oxygen measurement was used as electrochemical transducer. The results were compared with those obtained applying the Karl Fischer method to the same food or drug matrices. The correlations among the two methods proved satisfactory, as the difference in the computed values of water content was never higher than 7%. Also, the precision of measurements was acceptable (RSD < 6%) in all the analyses of real matrices. PMID- 11763069 TI - Effect of interfering substances on current response of recombinant peroxidase and glucose oxidase-recombinant peroxidase modified graphite electrodes. AB - Graphite electrodes have been modified with different forms of horseradish peroxidase (HRP). These included native HRP, wild-type recombinant HRP, and two single-point recombinant HRP mutants, N70V and N70D. The mediator-less response of these electrodes to H2O2 was studied indicating that electrodes modified with recombinant HRP forms are more stable than those modified with native HRP. Various interfering compounds were investigated for their effect on the current response to H2O2. It was found that interferences such as acetaminophen and dopamine affected the response by mediating the electron transfer (ET) between graphite and peroxidases. The mediating behaviour manifested itself as an increased current of the electrode to H2O2. The interfering effect was less pronounced for the electrodes modified with recombinant HRPs possessing better electronic coupling with the graphite surface. The interfering behaviour of acetaminophen on the response for glucose with the bienzyme electrode containing co-immobilised glucose oxidase and HRP was mainly ascribed to mediation of ET between graphite and HRP. It was experimentally proven that a high efficiency of direct ET between graphite and recombinant HRP substantially reduces the interfering effect of acetaminophen. PMID- 11763070 TI - Towards the development of molecularly imprinted polymer based screen-printed sensors for metabolites of PAHs. AB - This paper describes the fabrication of a sensor for 1-hydroxypyrene (1-OHP) based on a screen-printed carbon electrode (SPCE) modified with a molecularly imprinted polymer (MIP); 1-OHP was chosen as a model metabolite of polyaromatic hydrocarbons (PAHs). It was shown that 1-OHP could be readily oxidised at a plain SPCE and the electrochemical mechanism was found to involve an ECE (electron transfer-chemical reaction-electron transfer) process. The MIP for 1-OHP was prepared using only divinylbenzene (DVB) and styrene as monomers and the binding was only based on hydrophobic interactions. Batch binding studies revealed that optimum uptake of 1-OHP by the MIP occurred from solutions containing 35% water in methanol. Selectivity of the binding sites in the MIP was examined by performing uptake studies in the same solution containing either phenol or 1 naphthol; the specific binding of 1-OHP was twenty times greater than the former and five times greater than the latter. Preliminary calibration studies were performed with the MIP-SPCE using a two-step approach; accumulation was carried out in 35% water in methanol followed by measurement in 50% methanol-0.025 mol dm(-3) phosphate buffer pH 12. This two-step non-competitive affinity assay gave encouraging results and indicated potential for use in pollution studies. PMID- 11763071 TI - A new electrochemical enzyme-linked immunosorbent assay for the screening of macrolide antibiotic residues in bovine meat. AB - A new sensitive electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of two macrolides (erythromycin and tylosin) in bovine muscle was developed, using the mouse monoclonal antibodies anti-erythromycin and anti tylosin. The competitive indirect assay was performed using an erythromycin (or tylosin)-BSA conjugate as a coating molecule; after competition between free and coated analytes for the antibodies, the activity of the horseradish peroxidase labelled antiglobulins was measured electrochemically using 3,3',5,5' tetramethylbenzidine (TMB) as substrate. The detection limit of the assay was 0.4 ng ml(-1) for erythromycin and 4.0 ng ml(-1) for tylosin, while the sensitivity (25% inhibition concentration) was 1.4 ng ml(-1) for erythromycin and 13.0 ng ml( 1) for tylosin. The specificity of the assay was assessed by studying the cross reactivity of various macrolides other than erythromycin and tylosin. The results indicate that the monoclonal antibodies anti-erythromycin and anti-tylosin can readily distinguish the target compound from other macrolides, with the exception of roxithromycin, a semisynthetic macrolide antibiotic derived from erythromycin. Fortified and real samples were analysed by the developed ELISA method and results confirmed by micro-LC-MS-MS using an atmospheric pressure ionisation (API) source and an ionspray (IS) interface. The latter provides unequivocal identification and quantification of the analytes at the level of interest. The ELISA assay showed precision (RSD) values ranging from 6.3 to 11.4% for erythromycin and from 7.5 to 12.6% for tylosin; the accuracy (relative error, RE) ranged from -16.0 to -9.8% and from -9.5 to 8.0% for erythromycin and tylosin, respectively. All results obtained demonstrate that the electrochemical ELISA is a suitable method for a sensitive, simple, rapid and reliable screening of the two macrolides in animal tissues. PMID- 11763072 TI - Micro sequential injection: environmental monitoring of nitrogen and phosphate in water using a "Lab-on-Valve" system furnished with a microcolumn. AB - A "Lab-on-Valve" manifold operated in the micro sequential injection (microSI) mode was adopted to accommodate EPA-approved methods for spectrophotometric determinations of nitrate, nitrite and orthophosphate in the ppb (N or P) concentration range. A computer programmable microSI protocol, utilizing stopped flow within a copperized Cd-foil filled microcolumn was developed for nitrate reduction to nitrite with subsequent colorimetric measurement, yielding concentration ranges for nitrate of 100.0-4000.0 ppb (N) and for nitrite of 30.0 4000.0 ppb (N) and linear calibration responses of r2 = 0.9999 for nitrate and 0.9995 for nitrite. Using a stopped-flow reaction rate measurement, phosphate was determined in the range 1.0-30.0 ppb (P) with a calibration response of r2 = 0.9997. The technical improvement of this methodology, apart from micro miniaturization, is the use of the stopped-flow technique, that resulted in improved detection limits and allowed reagent consumption to be reduced 1500-fold compared with conventional procedure while the amount of metallic cadmium was reduced 20-fold compared with the EPA-approved continuous-flow assay. PMID- 11763073 TI - Velocity measurement of particulate flow in microfluidic channels using single point confocal fluorescence detection. AB - This article presents a non-invasive, optical technique for measuring particulate flow within microfluidic channels. Confocal fluorescence detection is used to probe single fluorescently labeled microspheres (0.93 microm diameter) passing through a focused laser beam at a variety of flow rates (50 nL min(-1)-8 microL min(-1)). Simple statistical methods are subsequently used to investigate the resulting fluorescence bursts and generate velocity data for the flowing particles. Fluid manipulation is achieved by hydrodynamically pumping fluid through microchannels (150 microm wide and 50 microm deep) structured in a polydimethylsiloxane (PDMS) substrate. The mean fluorescence burst frequency is shown to be directly proportional to flow speed. Furthermore, the Poisson recurrence time and width of recovered autocorrelation curves is demonstrated to be inversely proportional to flow speed. The component-based confocal fluorescence detection system is simple and can be applied to a diversity of planar chip systems. In addition, velocity measurement only involves interrogation of the fluidic system at a single point along the flow stream, as opposed to more normal multiple-point measurements. PMID- 11763074 TI - Calculation of the electrophoretic mobility of amines in methanol-aqueous electrolyte systems. AB - An equation for calculating the electrophoretic mobility of an analyte with respect to the concentration of organic modifier in mixed aqueous-organic modifier running buffer was derived from mixture response surface methodology. In order to assess the accuracy and predictability of the proposed model, the electrophoretic mobilities of four aliphatic amines and imidazole (background absorber) were measured in mixed water-methanol running buffer containing 0-100% v/v methanol by capillary zone electrophoresis with indirect UV detection. The accuracy of the proposed model was examined by fitting all the experimental data points. The predictability of the model was then evaluated by employing six training data points to compute the model constants, and the mobility at the other data points was predicted by the trained model. The proposed model gave accurate results for the correlation and prediction, with mean percentage errors for the amines studied of 0.6% to 0.5% and 1.5% to 1.1%, respectively. PMID- 11763075 TI - High performance liquid chromatographic determination of mazindol in human plasma. AB - A simple and convenient high performance liquid chromatographic method with UV detection is described for the determination of mazindol [5-(p-chlorophenyl)-2,5 dihydro-3H-imidazo[2,1-a]isoindol-5-ol] and its major metabolite, 2-(2 aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine (Met), in human plasma. The analytes were extracted with ethyl acetate from plasma samples and separated on a C18 column using acetonitrile-0.067 mol dm(-3) phosphate buffer (pH 3.5) (24 + 76 v/v) as a mobile phase. The eluates were monitored at 220 nm. Following complete validation and stability studies, the proposed method proved to be sensitive and precise. The limits of detection were 0.07 and 0.08 ng ml(-1) of plasma for mazindol and Met, respectively. The accuracy and recovery were in the ranges 94 102% and 91-102%, respectively, for both compounds. The intra- and inter-assay precisions were less than 7.6 and 9.2%, respectively, for both compounds. The stability of mazindol under different storage conditions, i.e., at room temperature (rt) and 4 degrees C and with freeze-thaw cycles, was also examined. Mazindol was unstable in plasma samples left at rt and 4 degrees C. The method was applied to the determination of mazindol and Met in the plasma of a patient treated for obesity with mazindol. PMID- 11763076 TI - Formation of artefacts during air analysis of volatile amines by solid-phase micro extraction. AB - Solid-phase micro extraction (SPME) is a promising technique for fast and low cost trace analysis. However, some limitations of the technique were encountered when using a PDMS (polydimethylsiloxane)/Carboxen fibre for sampling a mixture of volatile aliphatic amines in air. On the GC chromatogram, two supplementary peaks were noticed in addition to the analyte peaks, thus limiting qualitative and quantitative analysis in this particular case. This paper presents the investigations to identify the artefacts and determine the origin of their formation. First, GC-MS identification, by both electron impact and chemical ionisation modes, demonstrated that the two artefacts were unsaturated amines assumed to be formed by a dehydrogenation reaction of the target amines. This reaction was found to occur during thermal desorption of analytes in the GC injection port and to be catalysed by temperature and by metals consisting of the inox (stainless-steel) needle of the SPME device. It was also demonstrated that artefact formation was not significant when using PDMS or PDMS/divinylbenzene fibres. This difference with PDMS/Carboxen fibre can be explained by the high desorption temperature required for this fibre. Moreover, the microporosity of Carboxen induces a longer desorption time which increases the contact between analytes and inox and thereby enhances artefact formation. PMID- 11763077 TI - Trace level analysis of polycyclic aromatic hydrocarbons in surface waters by solid phase extraction (SPE) and gas chromatography-ion trap mass spectrometry (GC-ITMS). AB - Ontario Provincial Water Quality Objectives for polycyclic aromatic hydrocarbons (PAHs) in surface waters require low parts per trillion (ng L(-1))/high parts per quadrillion (pg L(-1)) detection limits. To meet these monitoring requirements, a solid phase extraction-gas chromatography-ion trap mass spectrometry (SPE-GC ITMS) method was developed. Seventeen priority PAHs commonly monitored in surface and drinking waters were examined using an external ionization ion trap mass spectrometer operated in selected ion monitoring (SIM) mode. Under 70 eV electron ionization (El) conditions, both the quantitative [M]+* ion and confirmatory [M - 2H]+* ion were formed in classical abundance ratios. Each of these ion species was isolated in the ion trap using a specific scan function. However, to overcome poor levels of confirmatory ion abundance which otherwise restrict PAH method detection limits (MDLs), the abundance of [M - 2H]+* ions was augmented during isolation by causing the dissociation of [M]+* with the broad-band waveform used for high mass ion ejection. Augmenting the [M - 2H]+* signal intensity facilitated the achievement of MDLs of approximately 1 ng L(-1). PAHs in surface water samples that were not detected by current Ontario Ministry of the Environment high-performance liquid chromatography (HPLC)-fluorescence and GC single-stage quadrupole mass spectrometry methods were detected and quantified using the ion trap mass spectrometry SIM method. The data produced by all three methods on natural water samples fortified at sub-parts per billion (ppb) levels were comparable. When applied to Standards Council of Canada/Canadian Association for Environmental Analytical Laboratories (SCC/CAEAL, www.CAEAL.ca) accreditation audit samples, the SPE-GC-ITMS method results met all performance evaluation criteria. PMID- 11763078 TI - Single-sided membrane introduction mass spectrometry for on-line determination of semi-volatile organic compounds in air. AB - Construction, optimization, and testing of a novel single-sided configuration for a semi-permeable [poly(dimethylsiloxane); PDMS] membrane introduction system for mass spectrometry is described. On-line detection of semi-volatile organic compounds of environmental interest is shown, including lindane (a pesticide), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) (an explosive), butylated hydroxytoluene (BHT) (an antioxidant), 1,2-dichlorobenzene, dimethylmethyl phosphonate (DMMP) (a chemical warfare agent simulant) and naphthalene. The technique has limits of detection in the sub-ppb range. with rise times of 4 to 7 s and fall times of 12 to 36 s and a response that is linear over 4 orders of magnitude (from 0.1 ppb to 1000 ppb for DMMP). The cycle time, from crude air sampling to acquisition of results, is approximately 1 min. No sample preparation is necessary. PMID- 11763079 TI - Development and validation of a method for the confirmation of nicarbazin in chicken liver and eggs using LC-electrospray MS-MS according to the revised EU criteria for veterinary drug residue analysis. AB - A method is described for the quantitative confirmation of 4,4' dinitrocarbanilide (DNC), the marker residue for nicarbazin in chicken liver and eggs. The method is based on LC coupled to negative ion electrospray MS-MS of tissue extracts prepared by liquid-liquid extraction. The [M-H]- ion at m/z 301 is monitored along with two transition ions at m/z 137 and 107 for DNC and the [M H]- ion at m/z 309 for the internal standard, d8-DNC. The method has been validated according to the new EU criteria for the analysis of veterinary drug residues at 100, 200 and 300 microg kg(-1) in liver and at 10, 30 and 100 microg kg(-1) in eggs. Difficulties concerning the application of the new analytical limits, namely the decision limit (CCalpha) and the detection capability (CCbeta) to the determination of DNC in both liver and eggs are discussed. PMID- 11763080 TI - Efficient and sensitive screening and confirmation of residues of selected polyether ionophore antibiotics in liver and eggs by liquid chromatography electrospray tandem mass spectrometry. AB - A method using liquid chromatography tandem mass spectrometry (LC-MS-MS) with electrospray (ES) for the determination of traces of narasin, monensin and salinomycin in chicken liver and eggs was developed, validated and used for routine surveillance. The essence of this paper is to demonstrate that one single method can serve very well for two entirely different purposes, i.e., screening and confirmation. Highly reliable confirmation of the identity at low concentrations was demonstrated when residues of narasin were detected and quantified (0.2 to 11 ng g(-1)) in 50% of the Swedish eggs analysed in 1999. Four daughter ions were detected with ion ratios meeting suggested confirmation criteria for the European Union, even at 0.2 ng g(-1). The method was found to be highly cost-effective since both screening and confirmation of 98 liver samples were performed in only two analytical runs (the Swedish national surveillance scheme of 1999, report level 5 ng g(-1)). The high performance of the method for the different applications was possible due to a combination of the power of ES LC-MS-MS, a procedure involving screening of pooled samples, and method optimisation of the work-up (automated solid phase extraction), LC and MS parameters. Validation data for narasin (0.5 to 20 ng g(-1)) in eggs are presented (accuracy 94 to 108%, relative standard deviation 4 to 10%, limit of detection 0.026 ng g(-1)). The time for an LC-MS-MS run was 4 min, corresponding to 48 s per sample in a pool. PMID- 11763081 TI - Approach to the determination of insulin-like-growth-factor-I (IGF-I) concentration in plasma by high-performance liquid chromatography-ion trap mass spectrometry: use of a deconvolution algorithm for the quantification of multiprotonated molecules in electrospray ionization. AB - The insulin-like-growth-factor-I (IGF-I) peptide is known to be a marker for growth hormone administration. The development of a quantification method by electrospray ionization mass spectrometry (ESI-MS) coupled with high-performance liquid chromatography (HPLC) is required. This paper describes a method to quantify IGF-I using the internal standard R3 IGF-I in its oxidized forms. A deconvolution software was used to quantify the set of multi-charged molecules recorded on an ESI ion trap mass spectrometer. The results (i.e., linearity, reproducibility and concentration range) were obtained on standard samples and the described LC-ESI-MS method should be applicable to biological samples. PMID- 11763082 TI - Generic microcystin immunoassay based on monoclonal antibodies against Adda. AB - A monoclonal antibody (clone AD4G2) was generated against a common part of microcystins and nodularins, the unusual amino acid Adda [(2S,3S,8S,9S)-3-amino-9 methoxy-2,6,8-trimethyl-10-phenyldeca-4E,6E-dienoic acid]. A direct competitive ELISA based on this antibody was developed and the cross-reactivity pattern was measured. Different toxins showed a very similar response. The assay provides therefore a sum parameter of microcystins, nodularins and peptide fragments containing Adda. The IC50 for microcystin-LR was 0.33 microg L(-1) which leads to a detection limit of 0.07 microg L(-1). This is well below the concentration of 1 microg L(-1) proposed by the World Health Organisation (WHO) as the limit for drinking water. Microcystin-LR spiked water samples in the concentration range between 0.1 and 1 microg L(-1) were measured and a mean recovery of 113+/-23% was found. The antibody is well suited for the determination of microcystins in drinking as well as surface water. PMID- 11763083 TI - Multivariate evaluation of factors influencing the performance of a formic acid biosensor for use in air monitoring. AB - A formic acid biosensor for air monitoring has been evaluated using chemometric methods. Using experimental design eleven factors that could influence the performance of the biosensor were examined. The response matrices consisted of six parameters (steady state currents at three different formic acid concentrations and response rates during changes in formic acid concentrations) describing the performance of the biosensor. The data were evaluated using a combination of principal component analysis (PCA) and multiple linear regression (MLR). To confirm the conclusions from the PCA-MLR partial least squares (PLS) was also used. The most important factor for the biosensor performance was found to be the enzyme concentration. Using the information from the chemometric analyses the optimum operation conditions for the biosensor were determined. The steady state currents were increased by 18-30% and the initial two response rates increased by 47-89% compared with a biosensor that had not been optimised. PMID- 11763084 TI - Cyclodextrin-modified biosensors: comparision of cyclodextrin-linked ferrocenes as mediators in sol-gel and screen-printed formats for sensing acetylcholine. AB - This work reports the comparison of a sol-gel and a screen-printed biosensor format using new mediators and a sensitive thin-film (ref. 1: P. Kataky and D. Parker, Analyst, 1996, 121, 1829) to enhance the sensitivity and stability of biosensors. The new mediators were per-alkylated cyclodextrin linked ferrocenes and a control, ferrocene aminocarboxylic acid. The thin film comprised a cocktail with polyurethane, plasticiser, lipophilic anion and a perethylated beta-CD. The analyte targeted was acetylcholine using the established horseradish peroxidase choline-oxidase-acetylcholine esterase relay. The screen-printed electrode format showed a marked decrease in oxidation potential, the magnitude of the shift depended on the structure of the mediator and the membrane covering. Although lower oxidation-potentials were observed with the sol-gel format sensors, their response was more akin to aqueous solution behaviour. Electrocatalytic currents were observed suggesting a highly efficient electron transfer process. PMID- 11763085 TI - Magnetic bead-based label-free electrochemical detection of DNA hybridization. AB - Magnetic bead capture has been used for eliminating non-specific adsorption effects hampering label-free detection of DNA hybridization based on stripping potentiometric measurements of the target guanine at graphite electrodes. In particular, the efficient magnetic separation has been extremely useful for discriminating against unwanted constituents, including a large excess of co existing mismatched and non-complementary oligomers, chromosomal DNA, RNA and proteins. The new protocol involves the attachment of biotinylated oligonucleotide probes onto streptavidin-coated magnetic beads, followed by the hybridization event, dissociation of the DNA hybrid from the beads, and potentiometric stripping measurements at a renewable graphite pencil electrode. Such coupling of magnetic hybridization surfaces with renewable graphite electrode transducers and label-free electrical detection results in a greatly simplified protocol and offers great promise for centralized and decentralized genetic testing. A new magnetic carbon-paste transducer, combining the solution phase magnetic separation with an instantaneous magnetic collection of the bead captured hybrid, is also described. The characterization, optimization and advantages of the genomagnetic label-free electrical protocol are illustrated below for assays of DNA sequences related to the breast-cancer BRCA1 gene. PMID- 11763086 TI - The electroanalytical detection and determination of copper in heavily passivating media: ultrasonically enhanced solvent extraction by N-benzoyl-N phenyl-hydroxylamine in ethyl acetate coupled with electrochemical detection by sono-square wave stripping voltammetry analysis. AB - N-benzoyl-N-phenyl-hydroxylamine dissolved in ethyl acetate was employed as a ligand for the solvent extraction of copper. Ultrasonic emulsification was shown to be effective both in the extraction of copper from an aqueous phase into ethyl acetate and its recovery or "back extraction" into a fresh clean aqueous solution. Experimental determination of thermodynamic parameters governing the extraction process via UV/visible spectroscopy is reported. This permitted theoretical predictions for the amount of copper transferred into the final aqueous solution to be fitted to experimental data. Quantitative analysis of copper removed via double sono-extraction from an aqueous medium hostile to voltammetric analysis proceeded via sono-square wave anodic stripping voltammetry analysis (sono-SWASV). This resulted in very high sensitivity in the relatively clean medium. The technique was then applied to the analysis of copper in the soft drink 'Ribena Light'. In the absence of sample preparation by solvent extraction sono-SWASV yields a measurable peak current for copper. However it is irreproducible and erratic due to passivating effects, possibly attributed to the sugars, natural flavourings and colourings present. Following sono-solvent extraction, the overall copper concentration could be obtained with a detection limit of 2 microg L(-1). Biphasic sono-extraction synergistically coupled with the recognized technique sono-SWASV presents an attractive technique for copper analysis in electrode passivating media. The technique necessarily removes contaminants present in the test solution since these will prefer to remain in the initial aqueous phase, or will transfer to the organic phase but are unlikely to be doubly transferred into the 'clean' final aqueous phase. PMID- 11763087 TI - Carbon paste electrode for trace zirconium(IV) determination by adsorption voltammetry. AB - A very sensitive and selective procedure was developed for trace measurement of zirconium based on the cathodic adsorptive stripping voltammetry of the zirconium alizarin red S(ARS) complex at a carbon paste electrode (CPE). The 2nd-order derivative linear scan voltammograms of the zirconium-ARS complex were recorded by a model JP-303 polarographic analyzer from 0.0 to -1.0 V (vs. SCE). Optimal analytical conditions were found to be: an acetic acid (0.1 mol l(-1))-potassium biphthalate (0.08 mol l(-1)) buffer solution (pH 4.8) containing 4.0 x 10-6 mol l(-1) ARS; accumulation potential, 0.0 V; accumulation time, 180 or 90 s; rest time, 10 s; scan rate, 250 mV s(-1). The results showed that the complex can be adsorbed on the surface of the CPE, yielding one peak at -0.51 V, corresponding to the reduction of ARS in the complex at the electrode. The detection limit was found to be 1.0 x 10(-10) mol l(-1) (S/N = 3) for 240 s accumulation. The linear range was 2.0 x 10(-10)-4.0 x 10(-7) mol l(-1). The developed method was applied to the determination of trace zirconium in the ore samples with satisfactory results. PMID- 11763088 TI - Determination of the complex stability of zinc with carbonic anhydrase in sea water. AB - Carbonic anhydrase (CA) is inactive unless associated with zinc, with possible substitution by cobalt. In this work, the complexation of zinc by CA was determined in sea-water using cathodic stripping voltammetry (CSV) with ligand competition. The zinc was found to be released from the CA over a period of 3 h when equilibrated with a competing complexing ligand and the complex was re formed with the CA when zinc was added. A value of 8.90+/-0.27 was found for logK'ZnCA where K'ZnCA is the conditional stability constant for the complex of Zn2+ with CA in pH 8 sea-water. A value for the molecular weight of CA was calculated from its equivalent ligand concentration (in nM) obtained by titrations with zinc at various CA concentrations (1-4 mg l(-1)). The value found (34740 g mol(-1)) for the molecular weight is consistent with values found previously by other methods (29000-31000 g mol(-1)) confirming that the stoichiometry of the complex between zinc and CA is 1:1. This work confirms that the zinc-CA complex is reversible and that the interaction between zinc and CA can be determined using CSV with ligand competition. PMID- 11763089 TI - Effect of dissolved CO2 on the potential stability of all-solid-state ion selective electrodes. AB - The influence of dissolved CO2 on the potentiometric responses of all-solid-state ion-selective electrodes (ISEs) was systematically examined with four different types of electrodes fabricated by pairing pH-sensitive and pH-insensitive metal electrodes (Pt and Ag/AgCl, respectively) with pH-sensitive and pH-insensitive ion-selective membranes (H+-selective membrane based on tridodecylamine and Na+ selective membrane based on tetraethyl calix[4]arenetetraacetate, respectively). The experimental results clearly showed that the carbonic acid formed by the diffused CO2 and water vapor at the membrane/metal electrode interface varies the phase boundary potentials both at the inner side of the H+-selective membrane (deltaE(in)mem) and at the metal electrode surface (deltaEelec). The potential changes, deltaE(in)mem and deltaEelec, occurring at the facing boundaries, are opposite in their sign and result in a canceling effect if both the membrane and metal surface are pH-sensitive. Consequently, the H+-selective membrane coated on a pH-sensitive electrode (Pt) tends to exhibit a smaller CO2 interference than that on a pH-insensitive electrode (Ag/AgCl). When the all-solid-state Na+ and K+ ISEs were fabricated with both pH-insensitive metal electrode and ion-selective membrane, they did not suffer from CO2 interference. It was also confirmed that plasticization of the PVC leads to increased CO2 permeation. Various types of intermediate layers were examined to reduce the CO2 interference problem in the fabrication of H+-selective all-solid-state ISEs. The results indicated that the H+-selective electrode needs an intermediate layer that maintains a constant pH unless the carbonic acid formation at the interfacial area is effectively quenched. PMID- 11763090 TI - A comparison of simple statistical methods for estimating analytical uncertainty, taking into account predicted frequency distributions. AB - Error in chemical analysis is propagated mainly by multiplication (not addition) of random, systematic and spurious errors. Individual random errors tend to have symmetrical frequency distributions but their combined error distribution has a positive skew. Certain systematic errors (bias) conceivably could have frequency distributions which would enhance or lessen the overall skew but they are unlikely to produce a truly normal distribution. Each analytical method, or modification of it, may produce a unique frequency distribution of results. Hence an ideal general statistical treatment of results cannot exist and the best practical compromise should be utilised. Three simple statistical treatments of data produced from various analytical models were compared, to identify the best compromise. Conventional statistics, with no transformation of data, generally treated low results too favourably and high results too harshly. Prior transformation of results to logarithms tended to do the reverse. Transformation of results to factors, followed by derivation of a robust standard deviation, treated the extremes more equally, if somewhat harshly. Factor statistics for precision have low sensitivity to outliers and the assigned true value and they offer a good compromise for the description of analytical data. PMID- 11763091 TI - Factor transformation to produce statistics describing the uncertainty of analytical data. AB - Analytical uncertainty produced by random error has a positively skewed distribution and accuracy and precision have non-linear scales. Compared with conventional statistics, factor transformation of the data allows more appropriate interpretation of results and facilitates graphical inspection of data. Statistics are compared for practical examples of performance in proficiency tests and of repeatability and reproducibility in collaborative studies. Factor transformation is shown to be applicable to wide ranges of analyte concentration and measurement precision. PMID- 11763092 TI - Statistical and probabilistic approaches to confidence intervals of linear calibration in liquid chromatography. AB - The aim of this paper is to compare the reliability of two approaches to estimate the 95% confidence intervals of linear calibration in real situations. One is the statistical approach, which is well known in statistics, and the other is the probabilistic approach, which is based on a theory to predict the precision of instrumental analyses mainly from signal and noise, called FUMI (Function of Mutual Information) theory. The high-performance liquid chromatographic determination of quisalofop and maltose is taken as an example. Calibration lines obtained under the same experimental conditions are superimposed on the 95% confidence intervals to investigate whether the resulting confidence intervals can include all the calibration lines reasonably. A pair of 95% confidence intervals (upper and lower limits) can be calculated from each calibration line, but varies from calibration line to calibration line, although obtained under the same experimental conditions. The variability and reliability of the 95% intervals are also examined. PMID- 11763093 TI - Application of SERS spectroscopy to the identification of (3,4 methylenedioxy)amphetamine in forensic samples utilizing matrix stabilized silver halides. AB - A method based on surface-enhanced Raman scattering (SERS) spectroscopy was developed to meet the need for the reliable and rapid identification of illicit drugs such as the 'designer drug' XTC, preferably to increase the security of legal certificates. A matrix stabilized silver halide dispersion on a microtiter plate is used as the SERS-active substrate, providing an easy to use system for sample preparation and probing by means of a Raman microscope. The potential of the method is demonstrated by applying it to the identification of the psychoactive ingredients of drug containing tablets which were confiscated by the local police at techno-music events. The samples of interest were 26 different brands of XTC tablets and several pieces of evidence (powders) containing amphetamine. For reference, we show SERS and Raman spectra of pristine amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4 methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethamphetamine. PMID- 11763094 TI - Rapid determination of sulfonated naphthalenes and their formaldehyde condensates in aqueous environmental samples using synchronous excitation fluorimetry. AB - Sulfonated naphthalenes and their formaldehyde condensates (SNFC) were determined in aqueous environmental samples by spectrofluorimetry. A clean-up step using n hexane to extract possibly interfering nonpolar compounds such as naphthalene is the only preparatory procedure. Synchronous excitation mode with a gammalambda of 105 nm allows the determination of SNFC in environmental samples without additional clean-up or analyte enrichment. Interferences by humic acids and nitrate occurred only at concentrations higher than 1 mg C L(-1) and 10 mg NO3- L(-1), respectively. The limit of detection was 0.2 microg L(-1), the average recovery was 104% and the confidence interval (95% certainty) was 24%. The response factor for the quantitative determination of total SNFC, depending on the distribution of the different SNFC components, was validated for groundwater from two field sites using an HPLC-FD (fluorescence detection) method as a reference method. PMID- 11763095 TI - X-ray fluorescence spectrometric determination of sulfur-containing anionic surfactants in water after their enrichment on a membrane filter as an ion-pair complex with a cationic surfactant. AB - Anionic surfactants containing sulfur in their structure were enriched on a mixed cellulose ester membrane filter (MF) by filtration as an ion-pair complex with a cationic surfactant. After their enrichment, the anionic surfactants were determined by X-ray fluorescence spectrometry of the sulfur enriched on the MF. A linear calibration was obtained over a concentration range from 0.05 to 0.8 mg L( 1) of sodium dodecyl sulfate as a standard material with less than 6% RSD. The detection limit based on 3s for the reagent blank was 2 microg L(-1). This method is very simple, rapid and highly selective for sulfur-containing surfactants, and does not require any organic solvent extraction. This method was applied to the determination of anionic surfactant in some urban river waters where domestic wastewater was discharged. The results were compared with those obtained by conventional solvent extraction-spectrophotometry. The distribution of the analyte complexes within the MF where the ion-pair was retained is also discussed. PMID- 11763096 TI - A novel fluorescence reagent, 10-hydroxybenzo[h]quinoline-7-sulfonate, for selective determination of beryllium(II) ion at pg cm(-3) levels. AB - A facile method has been developed for the highly sensitive and selective determination of ultratrace Be(II) ion using a new fluorimetric reagent, 10 hydroxybenzo[h]quinoline-7-sulfonate (HBQS), under extremely alkaline conditions, at pH 12.0. This reagent is quite suitable for the very small ion, Be(II), to form a 6-membered chelate ring, compatible with a high fluorescence yield. The stoichiometry of the chelate is 1:1 for Be-HBQS at pH 12.0. The calibration graph gave a wide linear dynamic range, 2-100 nmol dm(-3) of Be(II) ion with the detection limit (3s blank) of 0.52 nmol dm(-3), or 4.7 pg cm(-3). The excellent sensitivity and toughness toward the matrix influence were demonstrated using the artificial sample solutions for air-dust. Coupled with the simple masking procedure using EDTA, the method enables one to determine Be(II) ion at nanomolar levels in the presence of metals at the natural abundance levels in air-dust samples, typically Al, Ca, Cu, Fe, Mg, Pb, and Zn at 130, 150, 1.0, 70, 33, 3.0, and 8.0 micromol dm(-3), respectively, in the final solution. The proposed method was successfully applied to the determination of Be in urban air. PMID- 11763097 TI - o-Dianisidine: a new reagent for selective spectrophotometric, flow injection determination of chlorine. AB - A flow injection analysis (FIA) procedure for the determination of free chlorine in industrial formulations and water samples is proposed. The manifold is provided with a gas-diffusion unit which permits the removal of interfering species and also the preconcentration of chlorine. The determination of chlorine is performed on the basis of the oxidation by o-dianisidine as a chromogenic reagent to a coloured product which can be monitored at 445 nm. The method (for a preconcentration step of 60 s) is linear over the range 0.04-1.00 mg l(-1) of chlorine, the limit of detection is 0.04 mg l(-1), the reproducibility of the procedure (as RSD of the slope) is 3.7% for a series of four independent calibrations, the precision (as RSD of a series of 30 continuous FIA peaks of 0.56 mg l(-1) of chlorine) is 1.4% and the sample throughput is 40 h(-1). A detailed comparative study of the analytical characteristics of a single mono channel reverse FIA assembly and the same system but provided with a Fluoropore membrane filter of 0.5 microm pore size was performed to check the advantages of the new approach in terms of sensitivity, selectivity and limit of detection. PMID- 11763098 TI - Obtaining the 'best values' of stability constants: the protonation constants of five thioether carboxylates as a case study. AB - Computer speciation models often require large numbers of equilibrium constant values. For this purpose, state-of-the-art methods for experimental constant determination, best value constant selection from published values, and constant prediction based on quantitative structure-activity relationships, are evaluated through their application to the study of the protonation constants of five thioether carboxylates in aqueous solution at 37 degrees C and I = 150 mmol dm( 3) (NaCl). PMID- 11763099 TI - Mid-infrared difference-frequency generation source pumped by 1.1-1.5 micrometer dual-wavelength fiber amplifier for trace-gas detection. AB - Continuous-wave mid-infrared radiation near 3.5 micrometers is generated by difference-frequency mixing of the output of a compact 1.1-1.5 micrometer dual wavelength fiber amplifier in periodically poled LiNbO3. The diode side-pumped amplifier is constructed with double-cladding Yb-doped fiber followed by single mode Er/Yb codoped fiber. Output powers of as much as 11 microW at 3.4 micrometers are obtained, and spectroscopic detection of CH4 and H2CO is demonstrated. PMID- 11763100 TI - Comparative study of 137Cs partitioning between solid and liquid phases in Lakes Constance, Lugano and Vorsee. AB - The methodology for estimating radiocaesium distribution between solid and liquid phases in lakes is applied for three prealpine lakes: Lake Constance (Germany), Lake Lugano (Switzerland) and Lake Vorsee (Germany). It is based on use of the exchangeable distribution coefficient and application of the exchangeable radiocaesium interception potential (RIPex). The methodology was tested against experimental data. Good agreement was found between estimated and measured 137Cs concentrations in Lake Constance and Lake Lugano, whereas for Lake Vorsee a discrepancy was found. Bottom sediments in Lake Vorsee are composed mainly of organic material and probably cannot be described in terms of the specific sorption characteristics attributed to illitic clay minerals. PMID- 11763101 TI - A particle-tracking method for simulating the dispersion of non-conservative radionuclides in coastal waters. AB - A particle-tracking method has been used to simulate the dispersion of non conservative radionuclides in the sea. Three dimensional turbulent diffusion and the interactions between water, suspended matter and bottom sediments are simulated using a stochastic method. Kinetic transfer coefficients, as in finite difference models, are used to describe the transfers between the liquid and solid phases. Deposition of suspended matter and erosion of sediment are also included in the model. The method has been applied to simulate the dispersion of 137Cs and (239,240)Pu in the English Channel and the results have been compared with those of a finite difference model. The results from both techniques are, in general, in good agreement. PMID- 11763102 TI - The impact of phosphate loading activities on near marine environment: the Syrian coast. AB - The impact of loading cargoes of phosphate ore into ships on the near marine environment at the Syrian coast has been evaluated. Results have shown a significant enhancement of 210Po, 210Pb and other natural radionuclides in sediment and surface water inside the port area. The highest 210Po and 210Pb concentrations observed in sediment were found to be 170 and 64 Bq kg(-1) respectively, while 210Pb and 210Po concentrations in surface water ranged from 5 to 20 mBq l(-1) and 0.93 to 3.23 mBq l(-1). In addition, comparable values of 210Po and 210Pb for all marine organisms (algae, crab and fish) suggest that their use as indicators for phosphate pollution is not recommended. However, the effect of loading cargoes on the port marine environment of Tartous was found to be mainly related to wind direction where radioactive air particulate are either being dispersed to land or sea. PMID- 11763103 TI - Norm and associated radiation hazards in bricks fabricated in various localities of the North-West Frontier Province (Pakistan). AB - The activity concentrations of natural gamma-emitting radionuclides and associated radiation hazards due to 40K, 226Ra and 232Th have been measured in baked brick samples, collected from six highly populated areas of the North-West Frontier Province (NWFP) of Pakistan. For the detection, analysis and data acquisition, a high purity germanium (HPGe) detector coupled with a high resolution multichannel analyser (MCA) was used. The range of the average values of the activity concentrations due to 40K, 226Ra and 232Th were found to be 680.3 +/- 22.2-784.4 +/- 30.7 Bq kg(-1), 36.9 +/- 3.5-51.9 +/- 3.3 Bq kg(-1) and 52.5 +/- 3.6-67.6 +/- 3.1 Bq kg(-1), respectively. Radium equivalent (Ra(eq)) activities and various hazard indices were also calculated to assess the radiation hazards. All the brick samples showed Ra, activities within the limit (370 Bq kg(-1)) set by the Organization for Economic Cooperation and Development (OECD) countries. The results of different criterion formulae also complemented each other in this study. The derived data have been compared with the reported values for other countries of the world. PMID- 11763104 TI - Tissue free water tritium and organically bound tritium in the rice plant acutely exposed to atmospheric HTO vapor under semi-outdoor conditions. AB - Potted rice plants were exposed to atmospheric HTO in a box outdoors for 1 h at 9 different times from booting to yellow-ripe stages. It is indicated that the leaf TFWT concentration may reach equilibrium within 1 h in clear weather. The plant TFWT concentration decreased at a rapid rate for the first several hours and at a much slower rate thereafter. The decrease till harvest was by factors of 600 95,000 depending on the plant parts and exposure times. The time course of the ear OBT concentration was characterized by the exposure time. After exposure at the booting to heading stages, the leaf OBT concentration decreased rapidly for the first several hours and then very slowly. The plant OBT concentration was initially about 2 orders of magnitude lower, but at harvest an order of magnitude higher, than the TFWT concentration. The OBT concentration in hulled seeds at harvest varied with exposure times by a factor of 70, being highest in the exposure performed at the earlier stage of rapid grain growth. Also in this exposure, the plant total OBT was greatest due to the seed OBT. PMID- 11763105 TI - Selected bibliography. PMID- 11763106 TI - Three-dimensional ballistocardiography and respiratory motion in sustained microgravity. AB - BACKGROUND: We measured the three-dimensional ballistocardiogram (BCG) in a free floating subject in sustained microgravity during spaceflight to test the usefulness of such measurements for future non-invasive monitoring of cardiac function, and to examine the effects of respiratory movement on the BCG in three axes. METHODS: Acceleration was measured using a three-axis accelerometer fastened to the lumbar region of the subject while simultaneous recordings of ECG, and respiratory motion via impedance plethysmography were also made. Data were recorded during a 146-s period of inactivity on the part of the subject during which time there was no contact with the spacecraft. RESULTS: Total body motion due to respiratory activity was consistent with that calculated from the known action of the diaphragm and conservation of momentum. The accelerations due to cardiac activity, ensemble averaged over the R-R interval, were greatest along the head-to-foot axis. Maximum amplitude of the HIJK complex of the BCG generated by ventricular ejection was greatest in the head to foot axis (approximately 70 x 10(-3) m x s(-2)), but there were also substantial accelerations along the dorsoventral axis of up to 43 10(-3) m x s(-2), that are not measured interrestrial two-dimensional studies. The amplitude of the BCG was strongly affected by lung volume, with accelerations being reduced 50 to 70% between end inspiration and end-expiration. CONCLUSIONS: These data suggest a greatly reduced transmission of the cardiac motion to the body at end-expiration (FRC) than at higher lung volumes. The BCG might be further developed as a non-invasive means of monitoring parameters such as stroke volume in microgravity. PMID- 11763107 TI - Circulatory responses to orthostasis during alpha1-adrenergic receptor blockade at high altitude. AB - BACKGROUND: Increased blood level of norepinephrine, a primary alpha-adrenergic agonist, is associated with high-altitude exposure, and may help regulate key physiological functions (e.g., blood pressure). We hypothesized that blocking alpha1-adrenergic receptors would impair circulatory compensation for an orthostatic challenge to a greater extent at altitude than at sea level. METHODS: Sixteen healthy women (23 +/- 2 yr) were randomly assigned to receive either 2 mg prazosin (n = 8) or placebo (n = 8) t.i.d. (double-blind design) for 12 d at sea level and during the first 12 d of altitude residence (4300 m). Passive 60 degrees upright tilt was performed at sea level (10 d of treatment), and after 3 and 10 d at altitude. Mean arterial BP (MABP, via auscultation) and heart rate (HR, via ECG) were measured every min during 10 min each of supine rest and tilt. RESULTS: For the prazosin group compared with the placebo group: 1.) Supine and tilt MABP were consistently lower (p < 0.05) at sea level; 2.) MABP did not differ (p > 0.05) for either day at altitude; 3.) HR was similar for both positions at sea level and altitude; and 4.) MABP was consistently less only at sea level and HR was consistently greater only at altitude (both p < 0.05) in response to tilt. CONCLUSIONS: alpha1-adrenergic blockade altered MABP and HR responses to tilt at sea level and altitude, but circulatory responses to orthostasis were well maintained in both environments. At altitude, BP during tilt was sufficiently maintained by a compensatory increase in heart rate, likely mediated by parasympathetic withdrawal. PMID- 11763108 TI - Aeromedical management of U.S. air force aviators who attempt suicide. AB - BACKGROUND: Little has been published about the aeromedical management and disposition of aviators who attempt suicide, and almost no such information about military aviators exists in the open literature. The few available data are scattered and frequently anecdotal. METHODS: The authors reviewed all case reports of fliers evaluated at the USAF School of Aerospace Medicine's Aeromedical Consultation Service (ACS) between 1981-96 for possible return to flying duties after a suicide attempt, and prepared a representative case report. RESULTS: Between 1981 and 1996, the ACS evaluated 14 trained aviators (pilots and other aircrew members, excluding flight surgeons) who had attempted suicide. Of these, 11 (79%) ultimately received a recommendation for return to flying duties. CONCLUSIONS: In most instances the underlying stressors included failed intimate interpersonal relationships, administrative or legal problems, psychiatric disorders, death of spouse, or job conflicts. Evidence of abuse of alcoholor other substances was found in 54% of an earlier, larger data set of attempters. Some data on aircrew suicide completion were available and are reported. The top medical priorities after such attempts should be to diagnose what is wrong, and to treat it. In spite of the common assumption that a suicide attempt inevitably ends a military flying career, some attempters can return to safe and effective flying duty after appropriate psychotherapy. If the flier regains physical and mental health and maintains them for at least 6 mo after treatment, then that flier may be evaluated by an outside aeromedical psychiatric consultant such as the ACS (to avoid transference issues between flier and therapist) for possible return to flying duties. Waiver action should be based on the underlying psychiatric diagnosis, not the suicidal attempt itself. Follow-up may be accomplished through periodic mental health evaluations in conjunction with routine physical examination procedures. Issues involving substance abuse and security clearances must be handled through the appropriate channels. PMID- 11763109 TI - Alcohol and other risk factors for drowning among male active duty U.S. army soldiers. AB - BACKGROUND: Risk factors for drowning are largely undocumented among military populations. HYPOTHESIS: Accident report narratives will provide important information about the role of alcohol use and other behaviors in drownings among active duty male U.S. Army soldiers. METHODS: Using a case series design, we describe drowning deaths reported to the U.S. Army Safety Center (1980-1997), documenting associated demographic factors, alcohol use, and other risk-taking behaviors. RESULTS: Drowning victims (n = 352) were disproportionately young, black, and single, with less time-in-service, and no college experience. Most drownings occurred off-duty (89%). Alcohol use was involved in at least 31% of the cases overall. Alcohol use was also associated with a 10-fold increase in reckless behavior (OR 9.6, 95% Cl 4.5-20.7) and was most common among drownings in Europe (OR = 4.3, 95% Cl 1.5-13.4). Most drownings occurred where no lifeguard was present (68%), but almost two-thirds occurred in the presence of others, with CPR initiated in less than one-third of these cases. Drownings involving minority victims were less likely to involve alcohol, but more likely to occur in unauthorized swimming areas. While most drownings did not involve violations of safety rules, over one-third of the cases involved some form of reckless behavior, particularly for those under age 21. CONCLUSIONS: Intervention programs should be tailored to meet the needs of the demographic subgroups at highest risk since behavioral risk factors vary by race and age. CPR training and skills maintenance can improve survival rates. Narrative data are important for developing hypotheses and understanding risk factors for injuries. PMID- 11763110 TI - Antihypertensive therapy in critical occupations: studies with an angiotensin II antagonist. AB - OBJECTIVE: This study was performed to establish whether an angiotensin II antagonist modulates daytime sleepiness or performance. METHODS: The central effects of losartan (50 and 100 mg), as well as amlodipine (5 and 10 mg) and promethazine (10 mg), were studied in six healthy volunteers (aged between 20 and 27 (mean 24) yr). Digit symbol substitution, tracking, vigilance, immediate and short-term memory recall, complex reaction time, together with objective (daytime sleep latencies) and subjective measures of sleepiness, were measured 1.0 h before and 0.5, 2.0, 3.5, 5.0, 6.5, and 8.0 h after ingestion. The study was placebo-controlled and double-blind with a six-way crossover design. RESULTS: No changes in performance or in measurements related to sleepiness were observed with losartan (50 and 100 mg). Amlodipine (10 mg) impaired immediate memory and increased subjective sleepiness at 8.0 h (p < 0.05). Promethazine (10 mg) impaired vigilance and immediate memory recall and increased reaction time (basic and complex) from 2.0 to 6.5 h after ingestion, impaired tracking from 3.5 to 6.5 h and increased subjective sleepiness from 2.0 to 8.0 h (p < 0.05). CONCLUSION: The study suggests that an angiotensin II antagonist could prove useful for the treatment of hypertension in aircrew. PMID- 11763111 TI - Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition. AB - BACKGROUND: Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. METHOD: A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. RESULTS: Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. CONCLUSION: PB is well tolerated by healthy young people, even when twice the recommended military dose is administered. PMID- 11763112 TI - No effect of hypergravity on adult rat ventral horn neuron size or SDH activity. AB - BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions. PMID- 11763113 TI - A review of the relationship between patent foramen ovale and type II decompression sickness. AB - The significance of patent foramen ovale (PFO) in the pathophysiology of Type II decompression sickness (DCS) remains controversial. PFOs are common, occurring in approximately one quarter of the normal population, thus making right-to-left shunting of venous gas emboli (VGE) a theoretical concern in both hyper- and hypobaric situations. Despite this high prevalence of PFO in the general population, and the relatively common occurrence of venous gas bubbles in diving and altitude exposures, the incidence of Type II DCS in diving or with altitude is remarkably low. Although the literature supports a relationship between the presence and size of PFO and cryptogenic stroke, and an increased relative risk of Type II DCS with a PFO in divers, the absolute increase in risk accrued is small. Hence, the value of screening is also controversial. This paper presents a summary of the literature on PFOs and DCS in animals, and in human altitude and diving, focusing on the latter; as well the analogous literature on cryptogenic stroke. The results of an examination of the literature on detection of, screening for, and treatment of PFOs is also presented. PMID- 11763114 TI - Hearing loss in space. AB - BACKGROUND: Temporary and, in some cases, permanent hearing loss has been documented after long-duration spaceflights. METHODS: We examined all existing published data on hearing loss after space missions to characterize the losses. RESULTS: Data from Russian missions suggest that the hearing loss, when it occurs, affects mainly mid to high frequencies and that using hearing protection often might prevent the loss. Several significant questions remain about hearing loss in space. While the hearing loss has been presumed to be noise-induced, no clear link has been established between noise exposure and hearing loss during spaceflight. In one documented case of temporary hearing loss from the Shuttle Mir program, the pattern of loss was atypical for a noise-induced loss. Continuous noise levels that have been measured on the Mir and previous space stations, while above engineering standards, are not at levels usually associated with hearing loss in ground-based studies (which have usually been limited to 8 10 h exposure periods). Attempts to measure hearing in space using threshold based audiograms have been unsuccessful in both the American and Russian programs due to noise interference with the measurements. CONCLUSIONS: The existing data highlight the need for reliable monitoring of both hearing and noise in long duration spaceflight. PMID- 11763115 TI - Wireless telemetry and Internet technologies for medical management: a Martian analogy. AB - BACKGROUND: The NASA Haughton-Mars Project Base Camp on Devon Island, Canada (approximately 75 degrees north) was the site for transmission of vital signs from two "terranauts" (individuals who acted as Earthbound astronauts) back to the United States in (artificially delayed) real-time. METHODS: The subjects became "physiologic ciphers" for status monitoring using readily available technologies that affordably captured and distributed vital signs to a variety of platforms. This study of nominal monitoring and simulated medical emergency used wireless technologies and the Internet. RESULTS: Basic vital signs and images can be sent using wireless topologies and completely automated functions. Due to the lightweight transport requirements, existing low data rate connections can easily handle the volume of traffic. CONCLUSIONS: Monitoring, the health of space travelers will be an important component for both low-Earth orbiting spacecraft and long-term missions to distant planets. However, terrestrial applications represent the primary application of such technologies because the home can be a remote and hazardous environment as well. PMID- 11763116 TI - The benefits of integrating Internet technology with standard communications for telemedicine in extreme environments. AB - The ability to continuously monitor the vital signs of a person can be beneficial especially if the environment is hazardous or a person simply has general health concerns. We wanted to ascertain if, by integrating the Internet, ubiquitous switching technologies and off-the-shelf tools, this "suite of services" could provide a topology to enable remote monitoring in extreme and remote locations. An evaluation of this approach was conducted at the base camp of Mount Everest in the spring of 1999. Three climbers were outfitted with wireless, wearable sensors and transmitters for 24 h as they ascended through the Khumbu Icefall toward Camp One. The physiologic data was forwarded to the receiving station at Base Camp where it was forwarded to the U.S. mainland. Two of the three devices delivered physiologic data 95%-100% of the time while the third unit operated at only 78%. According to the climbers, the devices were unobtrusive, however, any additional weight while climbing Everest must provide advantage. PMID- 11763117 TI - Blood-injection-injury phobia in a commercial aviator: a case report. AB - A small percentage of the population suffers from blood-injection-injury phobia. These individuals can have vasodepressor syncope related to episodes when their phobia is triggered by a stimulus such as the sight of blood or receiving an injection. A case is presented in which a commercial aviator had a vasodepressor syncopal event during flight. She is referred for evaluation. A discussion of the diagnosis, disease, treatment, and follow-up recommendations are included. PMID- 11763118 TI - Granulomatous hepatitis due to sarcoidosis: a case report. AB - A Royal Australian Air Force transport pilot is discovered to have abnormal liver function tests during a routine aircrew medical examination. In the preceding 12 mo he had experienced minimal symptoms. Liver biopsy confirmed granulomatous hepatitis, the cause of which was determined to be sarcoidosis. Hilar and paratracheal lymphadenopathy were found on chest radiography. No overt evidence of other pulmonary, cardiac or ocular disease was found. This case illustrates the interesting problem of a clinically well aviator with biochemical abnormalities only, but at risk due to the potential presence of more widely disseminated sarcoidosis. PMID- 11763119 TI - Case report: myopic shift in a stable corneal graft following high altitude exposure. AB - Refractive changes in patients after radial keratotomy who are exposed to high altitudes have been reported previously. Hypoxic environments may cause corneal curvature changes in surgically altered corneas that result in refractive error shifts. We report a patient who experienced a partially reversible myopic shift in a previously stable corneal transplant after prolonged exposure to high altitude. PMID- 11763120 TI - Skeletal muscle catabolism at high-altitude--immunoprotective or immunodepressive? PMID- 11763121 TI - In response to the commentary on "screening EEG in aircrew selection: clinical aerospace neurology perspective":. PMID- 11763123 TI - Supporting the exploration of space. PMID- 11763122 TI - How micro-machined sensors are being used to help pilots. PMID- 11763124 TI - Actin monoubiquitylation is induced in plants in response to pathogens and symbionts. AB - Most dramatic examples of actin reorganization have been described during host microbe interactions. Plasticity of actin is, in part, due to posttranslational modifications such as phosphorylation or ubiquitylation. Here, we show for the first time that actins found in root nodules of Phaseolus vulgaris are modified transiently during nodule development by monoubiquitylation. This finding was extended to root nodules of other legumes and to other plants infected with mycorrhiza or plant pathogens such as members of the genera Pseudomonas and Phytophthora. However, neither viral infections nor diverse stressful conditions (heat shock, wounding, or osmotic stress) induced this response. Additionally, this phenomenon was mimicked by the addition of a yeast elicitor or H2O2 to Phaseolus vulgaris suspension culture cells. This modification seems to provide increased stability of the microfilaments to proteolytic degradation and seems to be found in fractions in which the actin cytoskeleton is associated with membranes. All together, these data suggest that actin monoubiquitylation may be considered an effector mechanism of a general plant response against microbes. PMID- 11763125 TI - Transgenic tobacco plants expressing the potato virus X open reading frame 3 gene develop specific resistance and necrotic ring symptoms after infection with the homologous virus. AB - Tobacco plants were transformed with the open reading frame 3 gene from Potato virus X (PVX) coding for the p12 protein. Although the transgenic plants exhibited a normal morphological aspect, microscopic examination revealed extensive alterations in leaf tissue structure. After being challenged with PVX, the transgenic plants showed resistance to PVX infection and formation of specific leaf symptoms consisting of concentric rings encircled by necrotic borders. These novel symptoms were accompanied by biochemical changes normally associated with the hypersensitive response (HR) and were absent in noninfected transgenic plants or in PVX-infected nontransgenic plants. No equivalent virus resistance was observed after inoculation with Tobacco mosaic virus or Potato virus Y, suggesting the presence of a specific resistance mechanism. Despite development of HR-like symptoms, systemic acquired resistance was not induced in PVX-infected p12 transgenic plants. No evidence of an RNA-mediated resistance mechanism was found. PMID- 11763126 TI - The Bradyrhizobium japonicum hsfA gene exhibits a unique developmental expression pattern in cowpea nodules. AB - The Bradyrhizobium japonicum host-specific fixation gene hsfA was identified as essential for nitrogen fixation on cowpea, but not required for nitrogen fixation on soybean or siratro. The DNA sequence of the hsfA promoter contains a consensus RpoN, -24/-12 binding site, suggesting the involvement of a regulatory protein that binds to an upstream activating sequence (UAS). To further explore the regulation of this interesting gene, serial deletions of the hsfA promoter were made and fused with the beta-glucuronidase (GUS) gene. The HsfA3 deletion, containing 60 bp 5' of the -24/-12 sequence, showed a similar level of GUS expression to that shown by the longest fusion construct (HsfA1), containing 464 bp of upstream sequence. In contrast, the HsfA4-GUS fusion, containing only 20 bp 5' of the -24/-12 region, showed no GUS activity, delimiting the location of a putative UAS to a 40-bp region. During nodule development, GUS expression first appeared in nodules 12 days postinoculation (dpi) and reached a maximum level of expression in approximately 17-day-old nodules. By 28 dpi, HsfA-GUS expression had returned to a low, basal level. These data were consistent with the detection of hsfA mRNA by in situ hybridization in 17-day-old nodules, but not in 28-day old nodules. In contrast to the stage-specific expression in cowpea, HsfA-GUS expression increased with nodule development in HsfA3-inoculated soybean. These data indicate that HsfA expression is regulated in cowpea in a unique developmental manner and that the DNA regulatory regions that control this expression are confined to a short, promoter-proximal region. PMID- 11763127 TI - The role of G protein alpha subunits in the infection process of the gray mold fungus Botrytis cinerea. AB - To identify signal transduction pathways of the gray mold fungus Botrytis cinerea involved in host infection, we used heterologous hybridization and a polymerase chain reaction (PCR)-based approach to isolate two genes (bcg1 and bcg2) encoding alpha subunits of heterotrimeric GTP-binding proteins. Both genes have homologues in other fungi: bcg1 is a member of the G alpha(i) class, whereas bcg2 has similarities to the magC gene of Magnaporthe grisea and the gna-2 gene of Neurospora crassa. Reverse-transcription (RT)-PCR experiments showed clearly that both genes are expressed at very early stages in infected bean leaves. Gene replacement experiments were performed for both genes. bcg1 null mutants differ in colony morphology from the wild-type strain, do not secrete extracellular proteases, and show clearly reduced pathogenicity on bean and tomato. Conidia germination and penetration of plant tissue is not disturbed in bcg1 mutants, but the infection process stops after formation of primary lesions. In contrast, bcg2 mutants show wild-type colony morphology in axenic culture and are only slightly reduced in pathogenicity. Complementation of bcg1 mutants with the wild-type gene copy led to the full recovery of colony morphology, protease secretion, and pathogenicity on both host plants. Application of exogenous cyclic AMP restored the wild-type growth pattern of bcg1 mutants, but not the protease secretion, implicating an essential role of BCG1 in different signaling pathways. PMID- 11763128 TI - Ornithine decarboxylase knockout in Tapesia yallundae abolishes infection plaque formation in vitro but does not reduce virulence toward wheat. AB - A knockout strain of Tapesia yallundae lacking the single ornithine decarboxylase (ODC) allele has been created by targeted gene replacement. A central region of the ODC gene was isolated by polymerase chain reaction with degenerate oligonucleotides and used to probe a lambda genomic library. The gene was sequenced, and the encoded ODC protein sequence was shown to be similar to those from other fungi. The functionality of the T. yallundae ODC was confirmed by complementation of an Aspergillus nidulans mutant (puA) strain devoid of ODC activity, restoring growth in the absence of exogenous polyamines. Transformation mediated gene replacement was used to create strains that were auxotrophic for putrescine and lack ODC coding sequences. ODC knockout strains were unable to differentiate infection structures after in vitro induction and showed an abnormal hyphal branching phenotype. Pathogenicity studies on these mutants showed that, surprisingly, they are not reduced in virulence compared with nondisrupted transformants. This suggests that the strains carrying an ODC disruption can obtain sufficient polyamines from the host plant for normal growth and differentiation and, therefore, that fungal ODC may not be a suitable target for fungicides. PMID- 11763129 TI - A highly efficient transposon mutagenesis system for the tomato pathogen Clavibacter michiganensis subsp. michiganensis. AB - A transposon mutagenesis system for Clavibacter michiganensis subsp. michiganensis was developed based on antibiotic resistance transposons that were derived from the insertion element IS1409 from Arthrobacter sp. strain TM1 NCIB12013. As a prerequisite, the electroporation efficiency was optimized by using unmethylated DNA and treatment of the cells with glycine such that about 5 x 10(6) transformants per microg of DNA were generally obtained. Electroporation of C. michiganensis subsp. michiganensis with a suicide vector carrying transposon Tn1409C resulted in approximately 1 x 10(3) transposon mutants per pg of DNA and thus is suitable for saturation mutagenesis. Analysis of Tn1409C insertion sites suggests a random mode of transposition. Transposition of Tn1409C was also demonstrated for other subspecies of C. michiganensis. PMID- 11763130 TI - Differential regulation of gene expression in the obligate biotrophic interaction of Uromyces fabae with its host Vicia faba. AB - Classical analysis of obligate biotrophic fungi revealed changes of enzyme activities or the concentration of metabolites in infected areas. However, due to the intricate integration of host and parasite metabolism, it was not possible to delineate the individual contributions of the two organisms. Here, we used reverse-transcription-polymerase chain reaction to monitor expression of genes from the rust fungus Uromyces fabae and its host Vicia faba. We focused on genes relevant for amino acid and sugar uptake and metabolism in both organisms. In the fungus, mRNA for plasma membrane ATPase was detected in spores and all infection structures. Two genes for fungal amino acid transporters showed dissimilar regulation. Transcripts for one were detected during all developmental stages, whereas those of the other appeared to be under developmental control. The latter result was also obtained for the so far only hexose transporter known from U. fabae and for one gene of the thiamine biosynthesis pathway. In the host plant, transcripts for two ATPases analyzed generally declined upon infection. Sucrose synthase expression increased in leaves, but decreased in roots. Transcript levels of glucose and sucrose transporter genes appeared unchanged. Markers for amino acid metabolism did not show a uniform trend: transcripts for asparagine synthetase increased, whereas those for two amino acid transporters either decreased or increased. Our analyses revealed that not only expression of genes in the immediate vicinity of the primary infection site is altered, but infection also influences transcription of certain genes in remote organs, like stems and roots. This demonstrates alterations in the source-sink relationships. PMID- 11763131 TI - A protein from the mold Aspergillus giganteus is a potent inhibitor of fungal plant pathogens. AB - A purified preparation of antifungal protein (AFP) from Aspergillus giganteus exhibited potent antifungal activity against the phytopathogenic fungi Magnaporthe grisea and Fusarium moniliforme, as well as the oomycete pathogen Phytophthora infestans. Under conditions of total inhibition of fungal growth, no toxicity of AFP toward rice protoplasts was observed. Additionally, application of AFP on rice plants completely inhibited M. grisea growth. These results are discussed in relation to the potential of the afp gene to enhance crop protection against fungal pathogens in transgenic plants. PMID- 11763132 TI - Potato spindle tuber viroid as inducer of RNA silencing in infected tomato. AB - Potato spindle tuber viroid (PSTVd), an RNA plant pathogen encoding no known proteins, induces systemic symptoms on tomato plants. We report detection of small RNAs of approximately 25 nucleotides with sequence specificity to PSTVd in infected plants: an indication of the presence of RNA silencing. RNA silencing, however, did not appear to be responsible for the differing symptoms induced by a mild and a severe strain of PSTVd. The unique structural and biological features of viroids make them attractive experimental tools to investigate mechanisms of RNA silencing and pathogen counterdefense. PMID- 11763133 TI - Novel genomic locus with atypical G+C content that is required for extracellular polysaccharide production and virulence in Xanthomonas oryzae pv. oryzae. AB - Three exopolysaccharide (EPS)- and virulence-deficient mutants of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight of rice, were isolated by Tn5 mutagenesis. These insertions are not located within the gum gene cluster. A 40-kb cosmid clone that restored EPS production and virulence to all three mutants was isolated, and the three transposon insertions were localized to contiguous 4.3- and 3.5-kb EcoRI fragments that are included in this clone. Sequence data indicate that two of the transposon insertions are in genes that encode a putative sugar nucleotide epimerase and a putative glycosyl transferase, respectively; the third insertion is located between the glycosyl transferase gene and a novel open reading frame (ORF). A 5.5-kb genomic region in which these three ORFs are located has a G+C content of 5-1.7%, quite different from the G+C content of approximately 65.0% that is typical of X. oryzae pv. oryzae. Homologues of this locus have not yet been reported in any other xanthomonad. PMID- 11763134 TI - Analysis of genes expressed during rice-Magnaporthe grisea interactions. AB - Expressed sequence tag (EST) analysis was applied to identify rice genes involved in defense responses against infection by the blast fungus Magnaporthe grisea and fungal genes involved in growth within the host during a compatible interaction. A total of 511 clones was sequenced from a cDNA library constructed from rice leaves (Oryza sativa cv. Nipponbare) infected with M. grisea strain 70-15 to generate 296 nonredundant ESTs. The sequences of 293 clones (57.3%) significantly matched National Center for Biotechnology Information database entries; 221 showed homologies with previously identified plant genes and 72 with fungal genes. Among the genes with assigned functions, 32.8% were associated with metabolism, 29.4% with cell/organism defense or pathogenicity, and 18.4% with gene/protein expression. cDNAs encoding a type I metallothionein (MTs-1) of rice and a homolog of glucose-repressible gene 1 (GRG1) of Neurospora crassa were the most abundant representatives of plant and fungal genes, comprising 2.9 and 1.6% of the total clones, respectively. The expression patterns of 10 ESTs, five each from rice and M. grisea, were analyzed. Five defense-related genes in rice, including four pathogenesis-related genes and MTs-1, were highly expressed during M. grisea infection. Expression of five stress-inducible or pathogenicity-related genes of the fungus, including two hydrophobin genes, was also induced during growth within the host. Further characterization of the genes represented in this study would be an aid in unraveling the mechanisms of pathogenicity of M. grisea and the defense responses of rice. PMID- 11763135 TI - The need for a new prospective population-based cohort in Japan. PMID- 11763136 TI - Baseline survey of JPHC study--design and participation rate. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - The data collection from cohort subjects at baseline is the core work for prospective study as well as follow-up. We set up 140,420 cohort subjects (68,722 men and 71,698 women) (61,595 in 1990 as Cohort I and 78,825 in 1993 as Cohort II) based on resident registry of 29 districts under 11 Public Health Center areas and baseline survey were submitted for them. The survey consisted of the following three components: (1) self-administered questionnaire survey, (2) collection of blood samples (plasma and buffy coat) for deep-freezed storage and (3) collection of health check-up data. All survey were completed during the first five year of each study. Among all cohort subjects, 113,461 (81%) (53,375 men and 60,086 women, 50,245 in Cohort I and 63,216 in Cohort II) returned the questionnaire and 49,011 (35%) (18,159 men and 30,852 women, 24,637 in Cohort I and 24,374 in Cohort II) provide their blood. The health check-up data were collected from 47,910 (34%) (17,276 men and 30,664 women, 23,311 in Cohort I and 24,599 in Cohort II). These data and blood samples serve as basis for the Japan Public Health Center-based prospective Study on cancer and cardiovascular diseases (JPHC Study). PMID- 11763137 TI - Study design and organization of the JPHC study. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - The Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study; formerly called "Koseisho Multipurpose Prospective Cohort Study") began in 1990 (Cohort I) and 1993 (Cohort II). The JPHC Study covers 11 public health center areas throughout Japan and includes a total of 140,420 residents. The study's design includes a baseline survey with a self-administered questionnaire on lifestyle and collection of blood and health checkup data; a follow-up system for mortality, migration, and incidence of cancer and cardiovascular diseases; an additional follow-up survey after 5 and 10 years; and distribution of a newsletter. The JPHC study is expected to provide evidence for the prevention and control of cancer and cardiovascular diseases in the 21st century. PMID- 11763138 TI - Dietary habits among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - Dietary habit is closely associated with development of cancer and cardiovascular diseases, however little prospective evidence has been published for Japanese, whose dietary habit is substantially different from Western countries. Therefore, frequencies of food consumption, food preference, cooking method and acceptance of dietary advice were investigated at the baseline by two kinds of self administered food frequency questionnaires. Dietary habits between urban and rural (Tokyo and Osaka vs. others), or between Okinawa and non-Okinawa revealed recognizable differences. The so-called westernized foods such as bread, beef and coffee were more consumed in the urban areas such as Tokyo and Osaka and also in Okinawa. The frequencies of salted food intake such as pickled vegetables and salted seafoods were remarkably low in Okinawa. Cooking methods for meats, seafoods and vegetables were also unique in Okinawa. No distinct geographical difference was shown in food preference and modification of dietary habit by dietary advice. PMID- 11763139 TI - Smoking and drinking habits among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - Smoking and drinking habits at baseline survey among 110,896 male and female residents aged 40-69 are reported as part of an ongoing prospective population based cohort in 11 geographically diverse health centers in Japan. The age adjusted proportion of current and former smokers was 54.8% and 21.8% in males and 8.3% and 2.1% in females, respectively. Mean age at initiation of smoking in males and females was 20.6 and 27.8 years of age, respectively. In males, the age adjusted proportion of those who drink almost daily was 49.1% and that of those who drink almost never was 19.7%, while in females, it was 5.9% and 71.6%, respectively. When compared by health center, the proportion of male current smokers was lower in Miyako and Ishikawa, both located in Okinawa Prefecture, while in females the proportion was higher in urban areas, such as Katsushika and Suita. The proportion of those who drink almost daily in males was higher in Yokote, Kashiwazaki, Katsushika and Suita, and lower in Ishikawa and Miyako, but in Ishikawa and Miyako, the proportion of those who drink at social events was higher. In females, the proportion of those who drink almost daily was higher in urban areas. There was substantial variation in the types of alcohol beverages consumed by males. In contrast, alcohol consumption in females comprised mainly beer. PMID- 11763140 TI - Health status, life habits, and social background among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - A self-reported questionnaire on the health status, life habits, and social background was conducted at baseline in the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases (JPHC study). This report presents the outcome of the study regarding past or family history of various diseases, medical treatment, life habits such as physical labor or sports, and social background among study participants. In both cohorts I and II, prevalent past and family history included hypertension, stroke, and cancer, whereas the prevalence of coronary heart diseases was historically low. The prevalence of a past history of hypertension and stroke was higher in the northern part of Japan, Ninohe, and Yokote, and lower in Okinawa, compared to the other districts. The prevalence of participants with a history of stomach cancer and liver cancer was higher in Arikawa than in other districts. The frequency of participants who took medication from doctors ranged from 20% to 30%, higher in the Tohoku areas, and lower in Okinawa compared to the other districts. All districts showed a high rate of over 70% for the participation rate for basic health examination conducted by the local government, The rate was particularly high in the Tohoku area where a high prevalence of a history of hypertension was found. The frequency of persons who had a chance to participate in sports or physical exercise was high in Okinawa and Suita subcohort 2, although the mean total physical activity (both at work and for leisure time) was lowest in the latter subcohort. No substantial differences were found in compositions of personality among districts. The frequency of more active and positive persons, however, was relatively higher in urban areas and lower in Okinawa compared to the other districts. The association between the differences of health status, life habits, and social background and the occurrence of various lifestyle-related diseases will be clarified in a follow-up study within the JPHC study. PMID- 11763141 TI - Baseline data of reproductive system in the JPHC study. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - Hormonal status in the body is closely related to the occurrence of estrogen related cancers. Baseline survey data about the female reproductive system in JPHC study showed different gynecological and gestational profiles in each study area. Late menarche (15-16 y/o) was characteristic in the rural areas. Earlier gestational age and larger number of children were also more common in the rural areas. Baseline survey data, including gynecological past history, frequency of examination for uterine cancers, and so forth, showed some profile of middle aged women in the different areas in Japan. PMID- 11763142 TI - Geographic characteristics and mortality profiles in the JPHC study. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - The study areas of the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study) are distributed throughout Japan and represent both rural and urban communities. These geographical differences yield considerable difference in population, culture, and lifestyle. The mortality rates in the study areas were apparently influenced by these factors. The pattern of standardized mortality ratios (SMRs) for all causes of death (cancer, heart diseases, ischemic heart disease, and cerebrovascular diseases) in each area was different. Age-standardized site-specific cancer mortality rates showed large variation even when compared with corresponding figures of prefectures in Japan. The areas of the JPHC study showed different patterns of SMR for major causes of death. The differences in site-specific cancer mortality rates for most of the sites are sufficient for epidemiological analyses. PMID- 11763143 TI - Standardization of laboratory test in the JPHC study. Japan Public Health Center based Prospective Study on Cancer and Cardiovascular Diseases. AB - The standardization committee has carried out standardization of 23 laboratories in the cohort area. They participated in the External Quality Control Survey by the Japan Medical Association. Most laboratories got A or B in evaluation criteria for most test items, but the results of AST, ALT and gamma-GTP were unsatisfactory. As for the lipid standardization, accuracy and precision of all 23 laboratories were satisfactory except for one. Close communication and collaborative study with reference laboratory improved the accuracy control. PMID- 11763144 TI - Anthropometric measures, blood pressure and major laboratory examination results in the health check-up examination among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. AB - Health check-up data were compared in all 11 populations included in the cohort. The collected sample size was 23,313 in Cohort I and 24,654 in Cohort II. Height was greater in two urban populations, and body mass index (BMI) was largest in the two populations in Okinawa prefecture. Blood pressure was higher in the populations in northeast part of Japan and Okinawa prefecture, and lower in Suita. Serum total cholesterol level was higher in Okinawa and two urban populations, and lower in the populations in northeast part of Japan, and in Arikawa and Saku. PMID- 11763145 TI - Recent trends in organochlorine residues in mussels (Mytilus edulis) from the Mersey Estuary. AB - Blue mussels (Mytilus edulis) taken from several sites in the Mersey Estuary, an urban-industrial water body in NW England, have been analyzed for residues of the persistent organochlorines, DDT, PCB congeners nos. 28, 52, 101, 118, 138, 153 and 180 (ICES7), and alpha-MHCH (alpha-methyl hexachlorocyclohexane). The concentration range for sigmaPCB (ICES7) was 13.9-34.9 microg kg(-1) in 1994 compared with 9.6-31.9 microg kg(-1) in 1998, whilst the equivalent concentrations of sigmaDDT were 8.9-32.4 microg kg(-1) and 4.5-16.8 microg kg( 1), respectively. The concentration of alpha-MHCH, an organochlorine largely restricted to the Mersey Estuary, was 1.2-11 microg kg(-1) in 1994 and 0.3-1.3 microg kg(-1) in 1998. At both sampling dates the inner estuary sites of Rock Ferry and Egremont were more contaminated than the outer estuary sites of New Brighton. Dove Point and Caldy Blacks. The lower concentrations of organochlorines in mussels in 1998 compared with 1994 are thought to be early evidence of significant improvements in water quality derived from major capital investment in the treatment of industrial effluents and sewage wastewater, linked to a combination of stricter legislative controls and the environmental benefits from the adoption of new, clean technologies in manufacturing. PMID- 11763146 TI - Atmospheric input of anthropogenic phosphorus to the northwest Mediterranean under oligotrophic conditions. AB - Phosphorus (P) concentration in the atmospheric aerosol was measured at a northwestern Mediterranean coastal site. Airborne P ranged between 25 and 85 ng m(-3) (geometric mean: 51 ng m(-3)). Due to a significant contribution (about 90%) of anthropogenic land-based source emissions, dry deposition velocities of 0.1-0.5 cm s(-1) were used to estimate a dry flux of 0.15-0.7 micromol P m(-2) day(-1). The theoretical impact of the dry flux on primary production (0.1-0.4 mg C m(-2) day(-1)) is 50-200-fold lower than that of a single significant wet event. The incineration plant of the Nice district is identified as a possible major source of airborne anthropogenic P. As the implementation of waste plants is currently expanding along the western European shores, the importance of the P atmospheric source to the western Mediterranean is likely to increase with time. PMID- 11763147 TI - Influence of age, sex and body condition on zinc, copper, cadmium and metallothioneins in common guillemots (Uria aalge) stranded at the Belgian coast. AB - The common guillemots, Uria aalge, found stranded at the Belgian coast, display high levels of Cu in both liver and kidneys. The condition index of the animals, defined as the ratio of liver to kidneys mass (Wenzel & Adelung, 1996, The suitability of oiled Guillemots (Uria aalge) as monitoring organisms for geographical comparisons of trace element contaminants. Archives of Environmental Contamination and Toxicology, 31, 368-377), influences both the metal concentration and its binding to metallothioneins (MT): the lower the condition index, the more emaciated the animals, and the higher the total Cu concentration and the concentration of Cu bound to MT. In less robust individuals, our results suggest that Cu could displace Zn from MT, rendering the Zn ions available to induce a new MT synthesis. Sex-related effects also emerged as significantly higher hepatic MT as well as Cu- and Zn-MT concentrations were found in emaciated male guillemots compared to females. In both organs, Cd concentrations remained low and typically demonstrated an age-dependent renal accumulation, with no noticeable effect of the condition index. As a whole, these results suggest that, for guillemots found stranded at the Belgian coast. Cu binding to hepatic and renal MT could function as a protective mechanism, rendering the metal ions unavailable to exert any cytotoxic activity. PMID- 11763148 TI - The North Cape oil spill: hydrocarbons in Rhode Island coastal waters and Point Judith Pond. AB - On 19 January 1996, the North Cape oil barge ran aground near Moonstone Beach, RI, and spilled over 2700 metric tons of No. 2 fuel oil during a severe winter storm. High winds and rough seas drove the oil into the water column, and the oil spread throughout Block Island Sound and into several coastal salt ponds. Over 50 water samples were collected from Point Judith Pond (PJP) and the southern coast of Rhode Island for four months after the spill and analyzed for polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs). These analyses revealed that at least 60 km2 of coastal waters were impacted from the spill. Maximum concentrations of sigmaPAHs and TPHs were 115 and 3940 microg l( 1), respectively. The percentage of sigmaPAHs relative to the TPHs for all samples varied from 0.2 to 43%, showing that there was no clear relationship between sigmaPAHs and TPHs for the whole dataset and likely resulting from spatial and temporal partitioning over the course of the spill. However, within the dataset, there were stronger correlations for distinct samples collected at similar locations and times. In PJP, water column concentrations of individual PAHs decreased at rates of 0.08-0.24 day(-1) and lower-molecular weight PAHs were removed faster than higher-molecular weight PAHs. PMID- 11763149 TI - Increasing imposex in populations of Bolinus brandaris (Gastropoda: Muricidae) in the northwestern Mediterranean. AB - The muricid gastropod Bolinus brandaris exhibited imposex, a phenomenon linked to the use of organotin biocides. Several stages of imposex development (1-5) could be distinguished and were documented with SEM-photographs for the first time in this species. Additional alterations of the genital tract in females (blocked vulva preventing copulation and deposition of egg capsules) and males (excrecences on the penis and vas deferens) were shown. Imposex intensity on the Catalan coast was very high. The frequency of imposex off Barcelona and Vilanova i la Geltru was 100%, with all females showing stage 4. Imposex frequency off Sant Carles de la Rapita was 99.7% and the VDS index scored 3.9. Despite regulations of TBT-containing antifouling paints in Spain since 1990, the present study revealed that frequency and intensity of imposex have increased on the Catalan coast, at least since 1997. However, at present, imposex does not apparently affect the population dynamics of B. brandaris in the studied area, since no serious consequences on female reproduction (only one case of female sterilization) were detected. Gonadal activity and oogenesis were not suppressed or supplanted by spermatogenesis. Sex ratios were not male-biased. Possible sources of organotin biocides are examined. PMID- 11763150 TI - Do endocrine disrupting chemicals threaten Mediterranean swordfish? Preliminary results of vitellogenin and Zona radiata proteins in Xiphias gladius. AB - Endocrine Disrupting Chemicals (EDCs) have the potential to alter hormone pathways that regulate reproductive processes in wildlife and fishes. In this research the hypothesis that Mediterranean top predator species (such as large pelagic fish) are potentially at risk due to EDCs is investigated. These marine organisms tend to accumulate high concentrations of EDCs such as polyhalogenated aromatic hydrocarbons (PHAHs). The potential effects of EDCs on a fish species of commercial interest, the top predator Xiphias gladius (swordfish), were investigated using vitellogenin (Vtg) and Zona radiata proteins (Zrp) as diagnostic and prognostic biomarkers. Dramatic induction of typically female proteins (Vtg and Zrp) was detected by ELISA and Western Blot in adult males of the species. These results are the first warning of the potential risk for reproductive function of Mediterranean top predators, and suggest the need for continuous monitoring of this fragile marine environment. PMID- 11763151 TI - Hepatitis C virus: prospects for future therapies. AB - Hepatitis C virus (HCV) infection is a major health crisis worldwide. Current treatment requires combination therapy with interferon-alpha and ribavirin. The low efficacy and poor tolerability of this therapeutic regimen has driven the search for safer and more effective medicines. This search has led to intense research efforts which have enhanced our understanding of HCV biology and to the development of a number of strategies for identifying new antiviral agents. At the same time, efforts have been directed towards improving the efficacy and tolerability of existing therapies. Recent developments in the area of modified interferons and research on virus-encoded and host drug discovery targets are reviewed here. Advances in the field of improved interferon-based treatments and the use of new antiviral agents in clinical trials gives cause for optimism in the clinical management of HCV infections. PMID- 11763152 TI - ISIS-14803 (Isis Pharmaceuticals). AB - Isis and Merck are developing an antisense oligonucleotide for the potential treatment of hepatitis C virus (HCV) infection [305306]. As of March 2000, the lead from this program, ISI-14803, was being studied in a phase I/II trial where it was administered in three weekly 2-h infusions for 4 weeks [327913], [357823]. Based on these results Isis plans to evaluate the potential of ISIS-14803 in single-agent trials and in combination studies with PEGylated interferon and ribavirin, and in studies that will examine longer-term dosing with both i.v. and s.c. administration [412920]. In January 2000, Isis signed a binding letter of agreement with Elan to form a new subsidiary of Isis to develop ISIS-14803 [351881], [362727]. In October 2001, Isis reported that it had earned a $1.5 million research milestone payment from Merck for progress in this collaboration [426015]. PMID- 11763153 TI - Pegasys (Hoffmann-La Roche). AB - Hoffmann-La Roche has developed a PEGylated interferon alpha-2a, Pegasys, for the potential treatment of chronic hepatitis C and hepatitis B virus infection. It was first approved in Switzerland in August 2001 [418260] and was expected to be launched in September/October 2001 [419333]. In May 2000, Roche submitted a BLA to the US FDA, for approval to market Pegasys for the treatment of chronic HCV infection in non-cirrhotic and cirrhotic patients with compensated liver disease [329872], [348368], [367781]. Approval was still pending in December 2000 [387363], [392481]. Roche expects the US launch to take place in the second half of 2001 [400857]. In April 2001, Roche received a complete response letter from the FDA for Pegasys and was working with the FDA to address the questions raised in the letter [407595], [418310]. In August 2001, Roche expected approval for HCV in the US in 2002 and for HBV in 2004 [419333]. At this time, Roche planned to file an sNDA for combination with ribavirin [421285]. By March 2001, EU and Canadian filings had been made [401793]. Roche also planned to launch the product for chronic HBV infection and various malignancies in 2004 and 2005, respectively [400857]. Pegasys was filed for registration in Brazil in the first part of 2000 [418310]. As of December 1999, the drug was in phase II for HCV infection in Japan. It is being developed by Nippon Roche, which intended to extrapolate foreign phase III data for use in an NDA application in Japan [351804]. As a result of a meeting of Japan's PMSB in March 2001, Pegasys may be given priority in the review of its NDA, if submitted [403782]. In August 2001, Schering-Plough entered into a licensing agreement with F Hoffman-La Roche Ltd and Hoffmann-La Roche Inc that settles all patent disputes regarding the two companies' PEGinterferon products. Under the terms of the agreement, Schering-Plough and Roche will cross license to each other all patents applicable to Peg-Intron and Pegasys. The settlement agreement also includes a Schering-Plough sublicense of Enzon's branched PEG patents to Roche [418935], [418956]. Roche is collaborating with Maxim Pharmceuticals to develop PEG-IFN alpha-2a in conjunction with Maxim's Maxamine [378609]. In July 1998, Hoffmann-La Roche and Weston Medical signed a global agreement to license INTRAJECT (Weston's single-use, disposable, prefilled, needle-free injector for subcutaneous delivery of injectable liquid pharmaceuticals) for delivery of Pegasys [292119]. In April 1999, ABN Amro predicted annual sales of SFr 25 million in 2000, rising to SFr 75 million in 2002 [328676]. In September 2000, Merrill Lynch predicted sales of SFr 70 million in 2001, rising to SFr 700 million in 2004 [383742]. In March 2001, Deutsche Bank estimated that the product has sales potential of SFr 1600 million [421009]. PMID- 11763154 TI - Biological activity of tyrosine kinase inhibitors: novel agents for psoriasis therapy. AB - Uncontrolled signaling from protein tyrosine kinases (PTKs) can lead to numerous proliferative and inflammatory diseases, and identification of the specific PTKs that play a key role in a defined disease could potentially lead to a selective therapeutic agent. In psoriasis, the balance of signals that regulate the homeostasis of normal epidermis is altered. Several lines of evidence suggest a role for the epidermal growth factor receptor (EGFR) system in this process. The PTK inhibitor from the tyrphostins family--AG-1571 (SU-5271) potently inhibits proliferation of psoriatic keratinocytes in excellent correlation with its EGFR kinase inhibitory activity, and was in clinical trials by SUGEN Inc. The recently developed in vivo models of psoriasis may become useful tools to evaluate PTK inhibitors to treat the disease and open a novel specific therapeutic approach. This article summarizes recent progress in the development of PTK inhibitors in the treatment of psoriasis. PMID- 11763155 TI - Targeting interleukin-2 as a treatment for psoriasis. AB - Interleukin (IL)-2 is known to play a key role in the pathophysiology of psoriasis by activating T-cells. In recent years, therapies have been developed to specifically prevent T-cell activation by blocking the production of IL-2 or by inhibiting its action. These new therapies are discussed. PMID- 11763156 TI - Targeting phospholipase A2 for the treatment of inflammatory skin diseases. AB - Due to the problems associated with current treatments for inflammatory disorders of the skin, the pharmaceutical industry has focused on novel ways to treat these disorders. Lipid-derived eicosanoids, which play an important role in the underlying inflammation in psoriasis and atopic dermatitis, can be derived from the phospholipase (PLA)-dependent production of arachidonate. In this review, the characteristics and promise of PLA, inhibitors, which have shown activity in preclinical models of skin inflammation are discussed along with the challenges the field faces in developing clinical candidates. PMID- 11763157 TI - Immunotherapeutic approaches for the treatment of malignant melanoma. AB - Clinical and laboratory observations suggest that host immunological responses may occasionally influence the course of melanoma, stimulating the investigation of immunotherapy approaches in this disease. Areas of active investigation have included recombinant cytokines, either alone or in combination with chemotherapeutic regimens or other biological response modifiers, such as vaccines, monoclonal antibodies, dendritic cells and gene therapy. To date, the benefit of these approaches in patients at high-risk of recurrence or advanced disease has been modest. Although many of these novel strategies are limited by weak antigen presentation, tumor-induced tolerance and tumor heterogeneity, it is possible that these approaches will prove more useful when given in combination. PMID- 11763158 TI - Mechanism of action of thiazolidinediones. AB - Type 2 diabetes is associated with multiple metabolic abnormalities including insulin resistance and the procoagulant state. Thiazolidenediones are an emerging class of insulin sensitizers which have the potential to mitigate many of the complications of diabetes. Mechanisms of action of the thiazolidenediones are discussed together with their possible pitfalls. Presently, evidence to clearly define the role of thiazolidenedionesfor the treatment of type 2 diabetes is lacking. PMID- 11763159 TI - Current and future treatment strategies for type 2 diabetes: the beta-cell as a therapeutic target. AB - Diabetes affects millions of people worldwide. The most common variants are type 1 diabetes with autoimmune destruction of the pancreatic beta-cells and type 2 diabetes with peripheral insulin resistance and beta-cell dysfunction. In spite of tremendous research, current pharmacological regimens are still sub-optimal for adequate blood glucose control. As a consequence, patients with diabetes are at significant risk for development of serious long-term complications, such as blindness and kidney disease. This review will discuss present and future strategies for the treatment of type 2 diabetes with a focus on the more recently recognized problems of beta-cell dysfunction and loss. The treatment strategies presented include promotion of beta-cell proliferation and differentiation by glucagon-like peptide 1 receptor agonists. PMID- 11763160 TI - Pramlintide (Amylin). AB - Pramlintide is a human amylin analog, under development by Amylin (originally in collaboration with Johnson & Johnson), as an adjunct with insulin for the potential prevention of complications of type I diabetes, and as a single agent for type II diabetes [279804], [295121], [305454]. In December 2000, Amylin submitted a US NDA seeking approval to market pramlintide as an adjunctive therapy for type 1 and 2 diabetics using insulin [392527]; the application was accepted for review by the FDA in January 2001 [396938], and was scheduled for review by the Endocrinologic and Metabolic Drugs Advisory Committee on July 26 2001 [408924]. In May 2001, Amylin submitted an MAA for pramlintide to the EMEA [411323] and in October 2001, Amylin received an approvable letter from the FDA for both Type I and insulin-using Type II diabetes; however, at this time, discussions with the FDA were ongoing regarding additional clinical work that was required before the NDA would be approved [425570]. PMID- 11763161 TI - Parkinson's disease and D1 dopamine receptors. AB - This article reviews the role of the D1-like dopamine receptors in Parkinson's disease (PD), an idea supported by the location of D1 receptors in key aspects of basal ganglia circuitry. The initial disappointing results with available partial D1 agonists have been replaced by optimism as newer full D1 agonists have been shown to be the only class of drugs that can decrease parkinsonism in primates to a degree comparable to levodopa. Most of the available D1 agonists, however, have been plagued by several problems, including poor bioavailability due, at least in part, to the necessity of a catechol function. Three other development issues that have hampered some members of this class are tolerance, hypotension and seizures, although some of the newer drugs entering early development may have escaped these problems. Finally, scientific advances have suggested that therapeutic profiles may be improved either by targeting only one of the two D1 like receptors or by developing drugs that can activate selectively only some D1 mediated functions. These examples suggest that it is highly likely that the immense therapeutic potential of D1 agonists will be realized both in PD and several other important CNS disorders before the end of the decade. PMID- 11763162 TI - NS-2330 (Neurosearch). AB - NeuroSearch is developing NS-2330, a compound that increases the activity of dopamine, norepinephrine and acetylcholine, as a potential therapy for Alzheimer's disease (AD) and Parkinson's disease (PD) [260782]. It is in phase II for AD [355341], and by March 2001 was also in a phase II tolerability trial in PD patients with dyskinesia. Phase III studies are expected to begin in the third quarter of 2002 [413151]. At this time, NeuroSearch was in licensing negotiations with a number of companies and had expected an agreement to be concluded within the first half of 2001 [401800]. In June 2001, NeuroSearch decided to continue the in-house development of NS-2330 provided that a capital increase could be effected on satisfactory terms [412065], [413151]. In August 2001, the company confirmed that it had raised these funds and phase III studies were planned for the third quarter of 2002 [420708]. In September 2001, WestLB Panmure predicted that NS-2330 had 12 and 15% probabilities of reaching market for its PD and AD indications, respectively. It also predicted that the drug would be launched in 2008 and 2007 for these indications, with market shares of 12.5 and 25%, respectively [423585]. PMID- 11763163 TI - TAK-147 (Takeda). AB - TAK-147 is a CNS-specific acetylcholinesterase inhibitor under development by Takeda as a potential treatment for Alzheimer's disease. By November 1999, it had entered phase III trials in Japan [348496]. In August 1999, Lehman Brothers predicted product launch in 2002, with potential peak sales of $250 million in 2012 [349228]. PMID- 11763164 TI - Overview: rational integration of agents directed at novel therapeutic targets into combination chemotherapeutic regimens. AB - The last decade has witnessed the introduction of a number of agents directed against novel targets into the therapeutic armamentarium for the treatment of cancer. These include agents that interrupt neoplastic cell-survival signaling or cell-cycle regulatory pathways, and differentiation-inducing agents. A common theme linking these agents is that disruption of signal-transduction-, cell-cycle progression- or differentiation-related pathways frequently leads to mitochondrial damage and apoptosis, and loss of neoplastic cell self-renewal capacity. It has also become apparent that these novel agents may, in a dose- and sequence-dependent manner, lower the threshold for conventional cytotoxic drug induced apoptosis, resulting in synergistic interactions. More recently, evidence has been accumulating that the judicious combination of agents that interrupt more than one signaling-, cell-cycle-regulatory- or differentiation-related pathway represents an extremely potent apoptotic stimulus for neoplastic cells. The development of rational chemotherapeutic regimens combining these novel agents with others in their class or with conventional cytotoxic drugs presents significant challenges, but offers significant opportunities for therapeutic advances in the treatment of human malignancies. A brief overview of the status of this field follows. PMID- 11763165 TI - The Hsp90 chaperone as a promising drug target. AB - Geldanamycin and radicicol, antibiotics produced by Streptomycetes and fungi, respectively, were originally discovered many years ago. Only recently was it discovered that they bind with high specificity within the ADP/ATP binding pocket of the Hsp90 molecular chaperone, thereby inhibiting the function of Hsp90. In eukaryotic cells Hsp90 catalyzes the final activation step of many of the most important regulatory proteins. Cells that lose this function are severely compromised and cannot progress through the cell cycle. In cell-culture systems, the administration of geldanamycin induces degradation of several signal transduction proteins of oncological importance. Hsp90 inhibitors are, therefore, now attracting considerable attention as potential antitumor agents; one geldanamycin derivative is already in phase I trials as an anticancer drug. These drugs may also have virucidal, antimalarial and ischemia-protective effects. PMID- 11763166 TI - Pemetrexed disodium (Eli Lilly). AB - Pemetrexed, a thymidylate synthase (TS) and transferase inhibitor, is in phase III trials with Eli Lilly as a potential treatment for several common solid tumors, including non-small cell lung cancer (NSCLC) and mesothelioma [321789], [410731]. Studies on pemetrexed have concluded that not only is the compound a TS inhibitor but also a potent inhibitor of human dihydrofolate reductase (DHFR). The results suggest that pemetrexed acts upon multiple intracellular targets and that the antitumor effect may be derived from its simultaneous inhibition of multiple folate-requiring enzymes [203662]: this compound has been designated as a multitargeted antifolate (MTA) [386680]. The drug also causes concentration- and time-dependent apoptosis [284380]. Other studies in which the 4-oxo group of the pyrimidine ring portion of pemetrexed was replaced with a hydrogen atom, demonstrated that the resulting analogs were potent DHFR inhibitors with very little activity against the enzymes glycinamide ribonucleotide formyltransferase (GARFT) and TS [310674]. In phase II European studies in 64 patients with advanced breast cancer, encouraging responses were seen in anthracycline-failure (23%) and anthracycline-refractory (19%) patients. Responses were observed in 28% of patients who had been previously treated with a taxane [326097]. Data from a phase II trial of pemetrexed (500 mg/m2 once every 21 days as a 10 min i.v. infusion) as a salvage therapy in advanced breast cancer showed that supplementation of the treatment regime with folic acid (FA) and vitamin B12 reduced its already manageable and tolerable toxicities [408821], [409650]. At doses of 500 mg/m2, the drug was also safely administered to 35 patients with impaired renal function [409953]. Phase I and II trials have shown that the main side effects include neutropenia, thrombocytopenia, mucositis, nausea and vomiting [203666], [272241]. Princeton University holds the patent rights to this drug under EP-00432677. In June 2001, Lilly expected to launch the product in 2003 [412318]. In February 1999, Lehman Brothers predicted launch of the drug in 2001 [319225]. In February 1999, Deutsche Bank predicted sales of $100 million in 2001 rising to $400 million in 2003 [316821]. In November 1999, Lehman Brothers estimated peak revenues in excess of $1 billion [348368]. By September 2001, Bear Stearns & Co predicted sales of $35 million in 2002, rising to $125 million in 2005 [422325]. PMID- 11763167 TI - Alanosine (UCSD). AB - Researchers at the University of California at San Diego (UCSD) are developing alanosine as a potential treatment for cancer [227466], [408222]. The compound was originally under development in collaboration with Triangle, which initiated its development in 1996 [227466], but later discontinued development of the compound [406677]. As of May 2001, UCSD's ongoing clinical trials of alanosine included phase II trials for non-small cell lung cancer (NSCLC) and phase I trials for acute lymphoid leukemia (ALL), while a phase II trial for glioma at UCSD had been suspended [408222]. Alanosine is an amino acid analog originally derived from Streptomyces alanosinicus. It interferes with the de novo synthesis of adenosine in both malignant and normal cells. In cancer cells that lack methyladenosine phosphorylase (MTAP, required in the salvage pathway), alanosine should deprive such cells (but not normal cells) of de novo synthesized adenosine [277968]. In early 1997, patients were being recruited for a phase II pilot efficacy trial of alanosine as a treatment for glioma and NSCLC, since a significant number of these tumor types lack MTAP and, it was hoped, would therefore be sensitive to alanosine [239280], [248260]. Phase I and II trials were completed in the 1980s by the NCI before they were discontinued because alanosine caused toxicity typically associated with chemotherapy, and did not produce significant response rates in common tumors such as breast or colon cancers. Researchers at UCSD found that some types of cancer lack MTAP, which was responsible for alanosine's previous clinical failure [227466]; phase II trials were being carried out at the university in 1997 [269338]. Triangle obtained an option for a worldwide license from the Regents of the University of California that expired in September 1998 (but had an option to extend the period for a further one year) [277968]. PMID- 11763168 TI - ET-743 (PharmaMar/NCI/Ortho Biotech). AB - Ecteinascidin-743 (ET-743), a tetrahydroisoquinoline alkaloid isolated from the Caribbean tunicate, Ecteinascidia turbinata, is under development by PharmaMar (the pharmaceutical subsidiary of Zeltia), the National Cancer Institute (NCI) and Ortho Biotech, as a potential treatment for several tumor types including breast cancer, lung cancer, ovarian cancer and melanoma. It appears to function by DNA minor groove alkylation, which induces topoisomerase I-mediated protein linked DNA strand breakage [322446]. ET-743 is an analog of ET-729 [169825]. As of February 1999, it was in phase II trials [326363], [326268], [375811] and, in August 2001, PharmaMar expected phase II trials for breast, ovarian and non-small cell lung cancer to be completed by August 2002 [423408]. In June 2001, the EMEA awarded ET-743 Orphan Drug status for the treatment of soft tissue sarcoma [412446]. The orphan medicinal product designation is designed to expedite the registration of pharmaceuticals for life-threatening or debilitating conditions with low prevalence (< 5 per 10,000 in the EU), for which no satisfactory treatment exists. The designation offers the sponsor several incentives, such as centralized procedure review of the Marketing Authorization Application and, upon approval, ten-year marketing exclusivity throughout Europe for the therapeutic indication for which it was granted. PharmaMar is also collaborating with the European Organization for Research and Treatment of Cancer (EORTC); PharmaMar has obtained the worldwide rights to ET-743, amongst other ecteinascidins, from the University of Illinois [177268]. In August 2001, Dresdner Kleinwort Wasserstein predicted total sales, for all ET-743's indications, of $1 million in 2002, rising through $1106 million in 2007 to $2725 million in 2011 [423408]. PMID- 11763169 TI - Expression of CD3 and CD11b antigens on blood and mammary gland leukocytes and bacterial survival in milk of cows with experimentally induced Staphylococcus aureus mastitis. AB - OBJECTIVES: To differentiate early (1 to 8 days) from late (9 to 14 days) inflammatory phases and assess relationships between leukocyte phenotype and bacterial recovery in cows with Staphylococcus aureus-induced mastitis. ANIMALS: 10 first-lactation Holstein cows. PROCEDURE: Blood and milk samples were collected from 4 or 6 cows before and after intramammary infusion of sterile broth or S. aureus, respectively. Flow cytometric expression of CD3 and CD11b antigens on blood and milk leukocytes, leukocyte differential counts, bacterial counts in milk, and somatic cell counts were determined longitudinally. RESULTS: Density of CD3 molecules decreased on blood lymphocytes and increased on milk lymphocytes after infusion of bacteria. Density of CD11b molecules on lymphocytes and phagocytes and percentage of CD11b+ lymphocytes in milk increased significantly after infusion; maximum values were achieved during the early inflammatory phase. Density of CD3 and CD11b molecules on milk lymphocytes and macrophages, respectively, 1 day after inoculation were negatively correlated with bacterial recovery on day 1 and days 9 to 14, respectively. Density of CD11b molecules on milk macrophages and the ratios of phagocyte to lymphocyte percentages and polymorphonuclear cell to macrophage percentages in milk differentiated the early from the late inflammatory phase. CONCLUSIONS AND CLINICAL RELEVANCE: Activation of bovine mammary gland macrophages and T cells in response to intramammary infusion of S. aureus was associated with an inability to culture this bacterium from milk. Identification of specific inflammatory phases of S. aureus-induced mastitis in cows may allow for the design of more efficacious treatment and control programs. PMID- 11763170 TI - Metabolism of amino acids in cats with severe cobalamin deficiency. AB - OBJECTIVE: To validate an automated chemiluminescent immunoassay for measuring serum cobalamin concentration in cats, to establish and validate gas chromatography-mass spectrometry techniques for use in quantification of methylmalonic acid, homocysteine, cysteine, cystathionine, and methionine in sera from cats, and to investigate serum concentrations of methylmalonic acid, methionine, homocysteine, cystathionine, and cysteine as indicators of biochemical abnormalities accompanying severe cobalamin (vitamin B12) deficiency in cats. SAMPLE POPULATION: Serum samples of 40 cats with severe cobalamin deficiency (serum cobalamin concentration < 100 ng/L) and 24 control cats with serum cobalamin concentration within the reference range. PROCEDURE: Serum concentrations of cobalamin were measured, using a commercial automated chemiluminescent immunoassay. Serum concentrations of methylmalonic acid, methionine, homocysteine, cystathionine, and cysteine were measured, using gas chromatography-mass spectrometry, selected ion monitoring, stable-isotope dilution assays. RESULTS: Cats with cobalamin deficiency had significant increases in mean serum concentrations bf methylmalonic acid (9,607 nmol/L), compared with healthy cats (448 nmol/L). Affected cats also had substantial disturbances in amino acid metabolism, compared with healthy cats, with significantly increased serum concentrations of methionine (133.8 vs 101.1 micromol/L) and significantly decreased serum concentrations of cystathionine (449.6 vs 573.2 nmol/L) and cysteine (142.3 vs 163.9 micromol/L). There was not a significant difference in serum concentrations of homocysteine between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cats with gastrointestinal tract disease may have abnormalities in amino acid metabolism consistent with cobalamin deficiency. Parenteral administration of cobalamin may be necessary to correct these biochemical abnormalities. PMID- 11763171 TI - Effects of exercise on biomechanical properties of the superficial digital flexor tendon in foals. AB - OBJECTIVE: To determine the effects of exercise on biomechanical properties of the superficial digital flexor tendon (SDFT) in foals. ANIMALS: 43 Dutch Warmblood foals. PROCEDURE: From 1 week until 5 months of age, 14 foals were housed in stalls and not exercised, 14 foals were housed in stalls and exercised daily, and 15 foals were maintained at pasture. Eight foals in each group were euthanatized at 5 months, and remaining foals were housed together in a stall and paddock until euthanatized at 11 months. After euthanasia, SDFT were isolated and fit in a material testing system. Mean cross-sectional area (CSA) was measured and traction forces recorded. Normalized force at rupture (force(rup)), normalized force at 4% strain, strain at rupture, stress at 4% strain (stress(4%stain)), and stress at rupture were compared among and within groups. RESULTS: At 5 months, mean CSA and normalized force(rup) were significantly greater and stress(4%strain) significantly less in the pastured group, compared with the other groups. At 11 months, CSA and normalized force(rup) were not significantly different among groups, because force(rup) increased significantly from 5 to 11 months in the nonexercised group and decreased significantly in the pastured group. CONCLUSIONS AND CLINICAL RELEVANCE: Exercise significantly affected the biomechanical properties of the SDFT in foals. Evenly distributed moderate- and low-intensity exercise at a young age may be more effective for development of strong, flexible tendons in horses than single episodes of high intensity exercise superimposed on stall rest. This effect may impact later susceptibility to SDFT injury. PMID- 11763172 TI - Computed tomographic study of the effect of a tongue-tie on hyoid apparatus position and nasopharyngeal dimensions in anesthetized horses. AB - OBJECTIVE: To determine the effect of manual tongue protrusion on the dimensions of the hyoid apparatus, nasopharynx, and oropharynx in anesthetized horses. tongue protrusion on the dimensions of the hyoid. ANIMALS: 5 adult horses. PROCEDURE: Horses were anesthetized and positioned in sternal recumbency for 2 sequential computed tomographic (CT) scans. Images were acquired with the tongue in a natural position inside the mouth. Then, the tongue was pulled rostrally and secured, and a second CT scan was performed. Dorsoventral length of the hyoid apparatus and angles of the basisphenoid, basihyoid, and ceratohyoid were measured on 3-dimensional reconstructed CT images. Cross-sectional diameters and areas of the nasopharynx and oropharynx were determined on reformatted images in the transverse and longitudinal planes, using osseous landmarks for consistency. Results were tested between the 2 groups to determine significant differences. RESULTS: We were unable to detect a significant difference between any of the lengths or angles of the hyoid apparatus measured with or without rostral protrusion of the tongue. Similarly, nasopharyngeal and oropharyngeal diameters and cross-sectional areas were not significantly different with or without rostral protrusion of the tongue. CONCLUSIONS AND CLINICAL RELEVANCE: Tying the tongue rostrally out of a horse's mouth did not influence the position of the hyoid apparatus or dimensions of the nasopharynx or oropharynx in anesthetized horses. Currently, no data suggest that application of a tongue-tie is effective for maintaining stability and patency of the nasopharyngeal or orolaryngeal airways in horses during races. PMID- 11763173 TI - Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals. AB - OBJECTIVE: To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. ANIMALS: 6 healthy 6- to 10-week-old foals. PROCEDURE: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. RESULTS: Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min x kg, and apparent volume of distribution at steady state was 18.6 L/kg. After i.g. administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated i.g. administration, peak serum concentration was 0.63 +/- 0.10 microg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated i.g. administration. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. PMID- 11763174 TI - Shedding of porcine reproductive and respiratory syndrome virus in mammary gland secretions of sows. AB - OBJECTIVE: To document shedding of porcine reproductive and respiratory syndrome (PRRS) virus in mammary gland secretions of experimentally inoculated sows, to evaluate effects of vaccination during gestation on virus shedding during the subsequent lactation, and to evaluate shedding of PRRS virus in milk of sows in commercial herds. ANIMALS: 6 sows seronegative for PRRS virus were used for experiment 1, and 2 sows were retained for experiment 2. For experiment 3, 202 sows in commercial herds were used. PROCEDURE: In experiment 1, 2 sows were inoculated with PRRS virus, 2 sows were vaccinated with modified-live PRRS virus vaccine, and 2 sows served as control pigs. Mammary gland secretions were assayed for PRRS virus. In experiment 2, pregnant vaccinated sows from experiment 1 were vaccinated with another modified-live PRRS virus vaccine. Mammary gland secretions were assayed in the same manner as for experiment 1. For experiment 3, milk collected from 202 sows in commercial herds was assayed for PRRS virus. RESULTS: In experiment 1, PRRS virus was detected in mammary gland secretions of both vaccinated and 1 of 2 virus-inoculated sows. In experiment 2, virus was not detected in samples from either vaccinated sow. In experiment 3, all samples yielded negative results. CONCLUSIONS AND CLINICAL RELEVANCE: Naive sows inoculated late in gestation shed PRRS virus in mammary secretions. Previous vaccination appeared to prevent shedding during the subsequent lactation. Results for samples obtained from sows in commercial herds suggested that virus shedding in mammary gland secretions of such sows is uncommon. PMID- 11763175 TI - Comparison of deposition images obtained by use of an ultrafine 99m-technetium labeled carbon dry aerosol with ventilation images obtained by use of 81m-krypton gas for evaluation of pulmonary dysfunction in calves. AB - OBJECTIVE: To characterize the accuracy of an ultrafine 99m-technetium-labeled carbon dry aerosol for use in assessment of regional ventilation in calves with pulmonary dysfunction. ANIMALS: 7 Belgian White and Blue calves. PROCEDURE: The ultrafine aerosol was assessed by comparing deposition (D) images with ventilation (V) images obtained by use of 81 m-krypton (81mKr) gas via D-to-V ratio (D:V) image analysis in calves during spontaneous breathing (SB) and during experimentally induced pulmonary dysfunction (ePD). RESULTS: Mismatching index (LrTot) calculated on the D:V images revealed a good match (LrTot, 0.96 +/- 0.01) between D and V distribution patterns in calves during SB. Calculation of the ultrafine aerosol penetration index relative to 81mKr (PIRel) revealed preferential distribution of the ultrafine aerosol in lung parenchyma (PIRel, 1.13 +/- 0.11). In ePD, heterogeneity in the D:V distribution was observed (LrTot, 0.78 +/- 0.10) as a result of ultrafine aerosol particles impaction in airways as indicated by PIRel (0.66 +/- 0.16) and a proportion of pixels more radioactive in D images, compared with V images, that was located in the central part of the lung (475 +/- 77% in ePD vs 32.8 +/- 5.7% in SB). However, this central deposition did not prevent visual examination of the entire ventilated lung. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrafine aerosol appears suitable for use in examination of ventilated parts of lungs of cattle, even those with impaired pulmonary function. However, airway impaction of ultrafine aerosol particles impedes the quantification of regional ventilation in cattle with abnormal lung function. PMID- 11763176 TI - Anticoagulant effects of repeated subcutaneous injections of high doses of unfractionated heparin in healthy dogs. AB - OBJECTIVE: To evaluate s.c. administration of unfractionated heparin (UFH) in accordance with a dosing regimen for high-dose treatment in dogs. ANIMALS: 10 healthy adult Beagles. PROCEDURES: Two groups of dogs (5 dogs/group) were given 6 injections of heparin (500 units of UFH/kg of body weight, s.c.) at intervals of 8 (experiment 1) and 12 (experiment 2) hours. Blood samples were collected before and 4 hours after heparin injections to determine amidolytic heparin activity, activated partial thromboplastin time (APTT), thrombin time, antithrombin activity, platelet count, and Hct. RESULTS: For experiments 1 and 2, mean +/- SD heparin activities before (experiment 1, 1.32 +/- 0.20 U/ml; experiment 2, 0.69 +/- 0.174 U/ml) and 4 hours after the last heparin injection (experiment 1, 1.71 +/- 0.30 U/ml; experiment 2, 1.10 +/- 0.30 U/ml) were higher than values calculated for the regimen used in experiment 1. Results of the investigated thrombin time test system with low thrombin activity were frequently beyond the measurement range, even with UFH activities > or = 0.6 U/ml. Moreover, a severe decrease of antithrombin activity became evident during both experiments (eg, in experiment 2 from 95.6 +/- 4.8 to 59.2 +/- 6.6%). In each treatment group, 2 dogs developed hematomas. CONCLUSIONS AND CLINICAL RELEVANCE: Calculations of the course of heparin activity after a single injection do not result in a reliable dosing regimen for high-dose heparin treatment in dogs. High-dose treatment must be monitored for each dog. Thrombin time measured with low thrombin activity is unsuitable for this purpose. PMID- 11763177 TI - Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis. AB - OBJECTIVE: To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. ANIMALS: 16 horses with recurrent uveitis. PROCEDURES: Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. RESULTS: The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). CONCLUSIONS AND CLINICAL RELEVANCE: This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis. PMID- 11763178 TI - Evaluation of an autogenous Salmonella bacterin and a modified live Salmonella serotype Choleraesuis vaccine on a commercial dairy farm. AB - OBJECTIVE: To compare the efficacy of a Salmonella bacterin and a modified live Salmonella ser. Choleraesuis vaccine on a commercial dairy. ANIMALS: 450 cows in late gestation and 80 calves. PROCEDURE: Group-1 cows (n = 150) were vaccinated once with a modified live S. Choleraesuis (serogroup C1) strain 54 (SC54) vaccine, group-2 cows (150) were vaccinated on enrollment and 30 days later with a Salmonella ser. Montevideo (serogroup C1) bacterin, and group-3 cows (150) served as unvaccinated controls. One gallon of colostrum harvested from the first 80 cows to calve was fed to each calf. Outcome assessments included fecal shedding of Salmonella spp for the first 10 days after parturition (cows) or birth (calves), milk production, involuntary culling rate, mastitis incidence, antimicrobial use, and mortality rate. RESULTS: Salmonellae were isolated from 306 of 309 (99%) cows and 64 of 74 (86.5%) calves. Shedding frequency was less in SC54-vaccinated cows and calves that received colostrum from those cows, compared with the other groups, and vaccination was specifically associated with less shedding of serogroup C1 salmonellae. Production data were similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination of pregnant cows with an autogenous Salmonella bacterin had no effect on fecal shedding of salmonellae, whereas vaccination with a modified live S. Choleraesuis vaccine reduced the frequency of fecal shedding of serogroup C1 salmonellae during the peripartum period. A commercial S. Choleraesuis vaccine licensed for use in swine may be more efficacious than autogenous Salmonella bacterins on dairies infected with serogroup C1 salmonellae. PMID- 11763179 TI - Cardiopulmonary function in horses during anesthetic recovery in a hydropool. AB - OBJECTIVE: To determine the cardiovascular and respiratory effects of water immersion in horses recovering from general anesthesia. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 3 times with halothane and recovered from anesthesia while positioned in lateral or sternal recumbency in a padded recovery stall or while immersed in a hydropool. Cardiovascular and pulmonary functions were monitored before and during anesthesia and during recovery until horses were standing. Measurements and calculated variables included carotid and pulmonary arterial blood pressures (ABP and PAP respectively), cardiac output, heart and respiratory rates, arterial and mixed venous blood gases, minute ventilation, end expiratory transpulmonary pressure (P(endXes)), maximal change in transpulmonary pressure (deltaP(tp)max), total pulmonary resistance (RL), dynamic compliance (Cdyn), and work of breathing (W). RESULTS: Immersion in water during recovery from general anesthesia resulted in values of ABP, PAP P(endXes), deltaP(tp)max, R(L), and W that were significantly greater and values of Cdyn that were significantly less, compared with values obtained during recovery in a padded stall. Mode of recovery had no significant effect on any other measured or calculated variable. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in pulmonary and cardiovascular function between horses during recovery from anesthesia while immersed in water and in a padded recovery stall were attributed to the increased effort needed to overcome the extrathoracic hydrostatic effects of immersion. The combined effect of increased extrathoracic pressure and PAP may contribute to an increased incidence of pulmonary edema in horses during anesthetic recovery in a hydropool. PMID- 11763180 TI - Computed tomography of the tarsal joint in clinically normal dogs. AB - OBJECTIVE: To use computed tomography to provide a detailed description of tarsal joint structures in clinically normal dogs. ANIMALS: 6 clinically normal adult mixed-breed dogs weighing 25 to 35 kg and one 12-month-old Bullmastiff weighing 65 kg. PROCEDURE: To perform computed tomography (CT) of both tarsal regions, dogs were anesthetized and placed in ventral recumbency. One- and 2-mm contiguous slices were obtained, using a third generation CT scanner Individual images were reviewed, using bone (window width = 3,500 Hounsfield units; window level = 500 Hounsfield units) and soft-tissue (window width = 400 Hounsfield units; window level = 66 Hounsfield units) settings. After euthanasia, the hind limbs from the Bullmastiff were removed and frozen at -18 C. Tarsal joints were sectioned into approximately 1-mm-thick slab sections, using a cryomicrotome. Anatomic sections were photographed and compared with the corresponding CT images. Computed tomographic reconstructions of the tarsocrural joint were created in sagittal and dorsal planes. RESULTS: Structures on the CT images were matched with structures in the corresponding anatomic sections. The entire tarsocrural joint surface could be evaluated on the reconstructed images in the sagittal and dorsal planes. CONCLUSIONS AND CLINICAL RELEVANCE: CT images provide full anatomic detail of the bony structures of the tarsal joint in dogs. Tendons and large blood vessels can also be evaluated. These results could be used as a basis for evaluation of CT images of the hind limbs of dogs with tarsal joint injuries. PMID- 11763181 TI - Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism. AB - OBJECTIVE: To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1beta in articular cartilage explants of horses. ANIMALS: 11 healthy 1- to 2-year-old horses. PROCEDURE: Horses were randomly assigned to the control (n = 5) or treated group (4.4 mg of phenylbutazone/kg of body weight, p.o., q 12 h; n = 6). Articular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment (day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with recombinant human interleukin-1beta (IL-1beta; 0.1 ng/ml). RESULTS: On day 0, proteoglycan synthesis was significantly less in cartilage explants cultured in IL-1beta, compared with medium alone. Mean proteoglycan synthesis in explants collected on days 14 and 30 was significantly less in treated horses, compared with controls. However, incubation of explants from treated horses with IL-1beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentration were not detected between or within groups. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of phenylbutazone for 14 days significantly decreased proteoglycan synthesis in articular culture explants from healthy horses to a degree similar to that induced by in vitro exposure to IL 1beta. Phenylbutazone should be used judiciously in athletic horses with osteoarthritis, because chronic administration may suppress proteoglycan synthesis and potentiate cartilage damage. PMID- 11763182 TI - Effects of acetylpromazine or morphine on urine production in halothane anesthetized dogs. AB - OBJECTIVE: To assess the influence of preanesthetic administration of acetylpromazine or morphine and fluids on urine production, arginine vasopressin (AVP; previously known as antidiuretic hormone) concentrations, mean arterial blood pressure (MAP), plasma osmolality (Osm), PCV, and concentration of total solids (TS) during anesthesia and surgery in dogs. ANIMALS: 19 adult dogs. PROCEDURE: Concentration of AVP, indirect MAP, Osm, PCV, and concentration of TS were measured at 5 time points (before administration of acetylpromazine or morphine, after administration of those drugs, after induction of anesthesia, 1 hour after the start of surgery, and 2 hours after the start of surgery). Urine output and end-tidal halothane concentrations were measured 1 and 2 hours after the start of surgery. All dogs were administered lactated Ringer's solution (20 ml/kg of body weight/h, i.v.) during surgery. RESULTS: Compared with values for acetylpromazine, preoperative administration of morphine resulted in significantly lower urine output during the surgical period. Groups did not differ significantly for AVP concentration, Osm, MAP, and end-tidal halothane concentration; however, PCV and concentration of TS decreased over time in both groups and were lower in dogs given acetylpromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Preanesthetic administration of morphine resulted in significantly lower urine output, compared with values after administration of acetylpromazine, which cannot be explained by differences in AVP concentration or MAP When urine output is used as a guide for determining rate for i.v. administration of fluids in the perioperative period, the type of preanesthetic agent used must be considered. PMID- 11763183 TI - In vitro responses of equine colonic arterial and venous rings to adenosine triphosphate. AB - OBJECTIVE: To evaluate the in vitro effects of adenosine tryphosphate (ATP) on vasomotor tone of equine colonic vasculature. SAMPLE POPULATION: Arteries and veins from the left ventral colon of 14 mixed-breed horses euthanatized for reasons unrelated to cardiovascular or gastrointestinal tract disease. PROCEDURES: Endothelium-intact and -denuded arterial and venous rings were precontracted with 10(-7) and 1.8 x 10(-8) M endothelin-1, respectively. In 1 trial, endothelium-intact rings were also incubated with 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME) to inhibit nitric oxide (NO) production. Adenosine triphosphate (10(-8) to 10(-3) M) was added in a noncumulative manner, and relaxation percentage versus time curves were generated. Areas under the curves (ie, percentage of relaxation time) were calculated. RESULTS: Relaxation response of arterial and venous rings to ATP was dose-dependent. Percentage of relaxation time in response to 10(-4) and 10(-3) MATP was significantly greater, compared with that for rings not treated with ATP Removal of endothelium attenuated but did not eliminate the relaxation response. Addition of L-NAME did not attenuate the relaxation response in arteries. At higher concentrations, the vascular response to ATP was biphasic. CONCLUSIONS AND CLINICAL RELEVANCE: ATP applied to equine colonic arterial and venous rings with and without intact endothelium induced a biphasic response characterized by transient contraction followed by slow, substantial, and sustained relaxation. This ATP-induced response is possibly mediated by a mechanism other than NO. Adenosine triphosphate may be a useful treatment to modulate colonic vasomotor tone in horses with strangulating volvulus of the ascending colon. PMID- 11763184 TI - Effects of vitamin E on urokinase-plasminogen activator receptor expression by bovine neutrophils. AB - OBJECTIVE: To determine the effect of vitamin E supplementation on urokinase plasminogen activator (u-PA) receptor (u-PAR) expression by neutrophils of dairy cows. ANIMALS: 16 healthy Holstein dairy cows. PROCEDURE: 16 cows were assigned to 1 of 2 experimental groups: control (no vitamin E supplementation) and vitamin E supplementation. Supplementation of vitamin E started 4 weeks prior to and continued up to 4 weeks after parturition and included oral administration of vitamin E at 3,000 U/cow per day; these cows also received 1 injection of vitamin E (5,000 units), 1 week prior to the expected date of parturition. Blood samples were collected, and neutrophils were isolated weekly throughout the experimental period. The following variables were measured: u-PA (mRNA), total cell-associated u-PA activity, membrane-bound u-PA activity, and free unoccupied u-PA binding sites on the cell membrane of neutrophils. RESULTS: Stimulated neutrophils isolated from cows that received vitamin E supplementation had significantly higher u-PA mRNA and total cell-associated and membrane-bound u-PA activity at postpartum week 1, compared with those of stimulated neutrophils isolated from control cows. There were no differences between groups throughout the whole experimental period in u-PA binding sites of neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: The increased total cell-associated and membrane-bound u-PA activity in neutrophils isolated from cows that received vitamin E may facilitate the ability of neutrophils to extravasate and reach the mammary gland at postpartum week 1. Rapid recruitment of neutrophils is critical for proper defense of the gland. PMID- 11763185 TI - Use of the 13C-octanoic acid breath test for assessment of solid-phase gastric emptying in dogs. AB - OBJECTIVE: To assess the 13C-octanoic acid breath test for determining gastric emptying in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Food was withheld for 12 hours before each test. Expired air was collected 30 minutes and immediately before each test and at frequent intervals thereafter for 6 hours. Concentration of 13CO2 in expired air was determined by use of continuous-flow isotope-ratio mass spectrometry. Basal concentration of 13CO2 was measured in dogs that were not fed a test meal. Effects of the standard unlabeled test meal on basal concentration of 13CO2 were then assessed. The optimum dose of substrate was determined by measuring 13CO2 concentration after ingestion of the standard test meal containing 50 or 100 mg of 13C-octanoic acid, whereas effect of energy density of the test meal on gastric emptying was determined after ingestion of the standard or high-energy labeled test meal. Gastric emptying coefficient (GEC), time to peak 13CO2 concentration (tmax), and half-dose recovery time (t(1/2)) were calculated. RESULTS: Basal concentration of 13CO2 in expired air was not significantly affected by ingestion of the unlabeled test meal. However, 13CO2 concentration significantly increased in a dose-dependent manner after ingestion of the labeled meal. Gastric emptying coefficient, and were significantly different between dogs fed the standard and high-energy test meals, indicating that ingestion of a high-energy meal delays gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: The 13C-octanoic acid breath test may be a useful noninvasive and nonradioactive method for assessment of gastric emptying in dogs. PMID- 11763186 TI - Effects of topical administration of 0.005% latanoprost solution on eyes of clinically normal horses. AB - OBJECTIVE: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. ANIMALS: 20 adult clinically normal horses. PROCEDURE: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement. RESULTS: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses. PMID- 11763187 TI - Serum lipid peroxide and alpha-tocopherol concentrations and superoxide dismutase activity in captive bottle-nosed dolphins. AB - OBJECTIVE: To evaluate serum lipid peroxide (LPO) and alpha-tocopherol concentrations and superoxide dismutase (SOD) activity in captive bottle-nosed dolphins and to evaluate effects of storage on production of LPO in various marine fish. ANIMALS: 16 bottle-nosed dolphins. PROCEDURE: 8 dolphins (group A) were fed chub mackerel and herring (high fat) and arabesque greenling and banded blue-sprat (low fat); the other 8 dolphins (group B) were fed chub mackerel and Pacific saury (high fat) and shishamo smelt and Japanese horse mackerel (low fat). Each group had been on these respective diets for 3 years. Serum LPO and alpha-tocopherol concentrations, serum SOD activity, and superoxide production by neutrophils were measured. All types of marine fish were frozen at -20 C for 6 months, and concentrations of LPO were measured at various time points. RESULTS: Serum LPO concentrations in group-A dolphins were significantly higher than those in group B. Serum alpha-tocopherol concentrations and SOD activity in group A were significantly lower than those in group B. A significant negative correlation was found between serum LPO and alpha-tocopherol concentrations in all 16 dolphins. The LPO concentrations in mackerel and herring fed to group-A dolphins were higher than those of other fish. Concentrations of LPO in herring stored for 3 and 6 months at -20 C were higher than those in herring before freezing and in herring stored for 1 month. CONCLUSIONS AND CLINICAL RELEVANCE: Serum LPO and alpha-tocopherol concentrations in captive bottle-nosed dolphins may be strongly influenced by high amounts of polyunsaturated fatty acid and LPO found in marine fatty fishes. High concentrations of serum LPO, as found in group A dolphins, were associated with decreased antioxidative states. Monitoring of serum LPO and alpha-tocopherol concentrations and serum SOD activity may be useful for the management of captive marine mammals. PMID- 11763188 TI - Investigation of mRNA expression of tumor necrosis factor-alpha, interleukin 1beta, and cyclooxygenase-2 in cultured equine digital artery smooth muscle cells after exposure to endotoxin. AB - OBJECTIVE: To determine messenger RNA expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin- (IL)-1beta from cultured equine smooth muscle cells (SMC). SAMPLE POPULATION: Segments of palmar digital artery harvested from 6 clinically normal adult horses. PROCEDURE: Explants were collected from the tunica media of arteries for primary culture of SMC. Equine mononuclear cells were used as control cells. Subcultured vascular SMC and control cells were exposed to lipopolysaccharide (20 microg/ml and 100 ng/ml, respectively). Northern blot analysis with equine-specific probes for COX-2, TNF alpha, and IL-1beta was performed, using isolated total cellular RNA. RESULTS: Although no message was detected for IL-1beta or TNF-alpha in control or endotoxin-exposed equine vascular SMC from all horses, COX-2 underwent a distinct substantial up-regulation after endotoxin exposure. Endotoxin-exposed equine mononuclear cells had up-regulation of IL-1beta and TNF-alpha mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: Increased expression of COX-2 mRNA by equine vascular SMC may be an important early pathophysiologic event in the onset of endotoxemia in horses. Potentiated local vascular production of various prostanoids after increased expression of mRNA for COX-2 may result in vasoactive events observed with laminitis. PMID- 11763189 TI - Evaluation of a short interspersed nucleotide element in the 3' untranslated region of the defective dystrophin gene of dogs with muscular dystrophy. AB - OBJECTIVES: To determine the distribution of a 231-base pair (bp) element in the dystrophin gene 3' untranslated region (UTR) in a colony of Golden Retrievers with muscular dystrophy and other unrelated dogs and to estimate the frequency of recombination for the canine dystrophin gene. ANIMALS: 77 dogs from the Golden Retriever Muscular Dystrophy (GRMD) colony at the Murdoch Veterinary School and 30 unrelated dogs from the Murdoch University Veterinary Clinic. PROCEDURE: Samples of blood or hair from dogs were used for amplification of DNA, using primers to the canine dystrophin 3' UTR. RESULTS: The DNA from affected dogs generated a larger PCR product than that obtained from clinically normal dogs. Products were cloned and sequenced, and the difference in size was found to be attributable to a 231-bp short interspersed nucleotide element (SINE). The SINE was found in all affected dogs in the colony but not in most unaffected puppies in the colony. Eighteen of 19 dogs in the colony were heterozygous for the GRMD mutation, and 7 of 30 unrelated dogs also were heterozygous for the SINE. CONCLUSION AND CLINICAL RELEVANCE: Evidence of recombination between the GRMD mutation and the SINE was observed in only 4 dogs (2 sets of littermates) in the GRMD colony. Incidence of this SINE in a few unrelated dogs suggests that this particular insertion into the dystrophin gene may have been a recent event. The SINE in the dystrophin 3' UTR did not have an apparent influence on dystrophin mRNA concentrations. PMID- 11763190 TI - Effects of racing and training on serum thyroid hormone concentrations in racing Greyhounds. AB - OBJECTIVES: To determine the effects of racing and training on serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations in Greyhounds. ANIMALS: 9 adult racing Greyhounds. PROCEDURE: Serum thyroid hormone concentrations were measured before and 5 minutes after a race in dogs trained to race 500 m twice weekly for 6 months. Resting concentrations were measured again when these dogs had been neutered and had not raced for 3 months. Postrace concentrations were adjusted relative to albumin concentration to allow for effects of hemoconcentration. Thyroid hormone concentrations were then compared with those of clinically normal dogs of non-Greyhound breeds. RESULTS: When adjusted for hemoconcentration, total T4 concentrations increased significantly after racing and TSH concentrations decreased; however, there was no evidence of a change in free T4 or total or free T3 concentrations. Resting total T4 concentrations increased significantly when dogs had been neutered and were not in training. There was no evidence that training and neutering affected resting TSH, total or free T3, or free T4 concentrations. Resting concentrations of T3, TSH, and autoantibodies against T4, T3, and thyroglobulin were similar to those found in other breeds; however, resting free and total T4 concentrations were lower than those found in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Except for total T4, thyroid hormone concentrations in Greyhounds are affected little by sprint racing and training. Greyhounds with low resting total and free T4 concentrations may not be hypothyroid. PMID- 11763191 TI - Effects of intestinal ischemia on in vitro activity of adjacent jejunum in samples obtained from ponies. AB - OBJECTIVE: To determine whether intestinal ischemia would alter activity of the jejunum in vitro or alter staining characteristics for certain types of enteric neurotransmitters. SAMPLE POPULATION: Jejunal samples obtained from 10 ponies. PROCEDURE: Jejunal samples were obtained from locations proximal and distal to an area of small intestine made ischemic for 60 minutes. A portion of each sample was stained to detect substance P-like immunoreactivity, cholinergic and adrenergic neurons, and nitric oxide synthase. Portions of the remaining samples were suspended in muscle baths. General activity patterns (frequency and amplitude of contraction), responses to neuronal depolarization induced by electrical field stimulation (EFS), and responses to 1 microM norepinephrine (NE) were compared with responses of a normal section of small intestine obtained prior to ischemic insult. RESULTS: Staining patterns were not altered. Proximal and distal sections had evidence of decreased contractility, compared with the normal section. Contraction frequency also was decreased, and distal sections had lower contraction frequency than proximal sections. Relaxation responses were decreased in distal sections. Responses to NE differed significantly for distal and proximal sections, compared with normal sections. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term ischemia can significantly affect adjacent bowel. Contractile and relaxation responses are impaired. Discrepancies in intestinal motility patterns and alterations in response to NE for sections proximal and distal to ischemic intestine could lead to clinical ileus or slowed transit of ingesta. PMID- 11763192 TI - Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration. AB - OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of danofloxacin in goats and the concentrations required to induce bacteriostasis, bactericidal activity, and bacterial elimination. ANIMALS: 6 healthy British Saanen goats. PROCEDURE: Danofloxacin (1.25 mg/kg of body weight) was administered i.v. and i.m. in a cross-over design with 14 days between treatments. A tissue cage was used for evaluation of drug distribution into transudate and exudate. The ex vivo antibacterial activity of danofloxacin in serum, exudate, and transudate against a caprine isolate of Mannheimia haemolytica was determined. Pharmacokinetic and pharmacodynamic data were integrated to determine the ratio of the area under the concentration versus time curve to the minimum inhibitory concentration of danofloxacin (AUIC). RESULTS: Elimination half-lives of danofloxacin in serum were 4.67 and 4.41 hours after i.v. and i.m. administration, respectively. Volume of distribution was high after administration via either route, and bioavailability was 100% after i.m. administration. Rate of penetration into exudate and transudate was slow, but elimination half-lives from both fluids were approximately twice that from serum. Drug concentrations in serum, exudate, and transudate for 9 to 12 hours after administration induced marked ex vivo antibacterial activity. For serum, AUIC24h values required for bacteriostasis, bactericidal effect, and bacterial elimination were 22.6, 29.6, and 52.4, respectively. Similar values were obtained for exudate and transudate. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of danofloxacin pharmacokinetic and pharmacodynamic data obtained in goats may provide a new approach on which to base recommendations for therapeutic dosages. PMID- 11763193 TI - Comparison of endogenous feline leukemia virus RNA content in feline vaccine and nonvaccine site-associated sarcomas. AB - OBJECTIVE: To determine whether feline vaccine site-associated sarcomas (VSS) contain a higher amount of endogenous FeLV (enFeLV) RNA, compared with feline nonvaccine site-associated sarcomas (non-VSS). SAMPLE POPULATION: Formalin-fixed paraffin-embedded (FFPE) tissues from 50 VSS and 50 cutaneous non-VSS. PROCEDURE: RNA was extracted from FFPE sections of each tumor, and regions of the long terminal repeat (LTR) and envelope (env) gene of enFeLV were amplified by use of reverse transcriptase-polymerase chain reaction (RT-PCR). The density of each RT PCR product band for enFeLV was compared with that of a constitutively expressed gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). An integrated density value (IDV) was determined by use of densitometry, and the IDV ratio for enFeLV to GAPDH was calculated for each enFeLV primer set. RESULTS: The median (interquartile range) of the IDV ratio for the enFeLV LTR primer set was 0.52 (0.26 to 1.17) for the VSS group and 0.84 (0.21 to 1.53) for the non-VSS group. The median (interquartile range) of the IDV ratio for the enFeLV env primer set was 0.60 (0.37 to 0.91) for the VSS group and 0.59 (0.36 to 1.09) for the non-VSS group. CONCLUSIONS: Because the amount of enFeLV RNA within the LTR and env gene was not significantly different between the VSS and non-VSS groups, enFeLV replication or expression is unlikely to be involved in VSS development. PMID- 11763195 TI - Actin cytoskeleton role in the structural response of epithelial (MDCK) cells to low extracellular Ca2+. AB - Kinetic and stereometric assessment of the mechanical responses of epithelial cells to variations in the concentration of extracellular Ca2+ was carried out in vivo at the single cell level. Continuous monitoring of individual MDCK cells in subconfluent cultures attested to an intense, immediately relaxable, and cytochalasin D-sensitive contraction, equivalent to that seen in confluent monolayers following depletion of external Ca2+ (<0.1 mM). Increasingly greater and less readily reversible contractions were performed upon repeated stimulation with short-term cycles of alternating normal (30 min) and low Ca2+ (30 min) media. Constriction of a narrow horizontal girdle corresponding in position to the major ring-like bundle of actin filaments eventually develops into a deep lateral furrow in intensely contracted cells. Substantial membrane infolding in the contracted state is indicated also by stereometric estimates of apparent bounding surface area. Irrespective of the contracted or relaxed cell condition, rhodamine-phalloidin labeling showed a marginal position of the ring-like bundle of microfilaments and other components of the actin cytoskeleton. These results suggest, contrary to prevalent views, that the actin-myosin system stays associated to the cortex and retains contractile capability in epithelial cells deprived of external Ca2+. Hence, the mechanical responses to variations of Ca2+ may be an overstrained expression of a physiological mechanism. PMID- 11763194 TI - Three-dimensional study of the capillary supply of skeletal muscle fibres using confocal microscopy. AB - Three-dimensional (3D) study of capillary network of individual muscle fibres in rat extensor digitorum longus (EDL) and soleus (SOL) muscles is presented. Stereology and 3D reconstruction techniques were applied to stacks of serial optical sections recorded by a confocal microscope from thick muscle slices. The results suggest that SOL muscle fibres have a larger surface area and volume as well as a larger length of capillaries per fibre length than EDL. On the other hand, these two muscles have a similar ratio of capillary length to fibre surface area. The 3D approach to evaluation of muscle fibre capillarization brings many advantages over traditional measurements made on single muscle sections and could also be applied to the study of angiogenesis in other tissues. PMID- 11763196 TI - Protein kinase C mediates phosphorylation of the regulatory light chain of myosin II during mitosis. AB - Phosphorylation of the regulatory light chain (RLC) of myosin-II is cell cycle dependent. Early in mitosis the RLC is phosphorylated predominantly on Ser-1/2, while during cytokinesis the primary site of phosphorylation is Ser-19 (Yamakita et al., 1994). To identify candidate kinases likely to mediate the mitotic phosphorylation on Ser-1/2, we assayed RLC kinase activity in mitotic cell extracts and measured apparent steady-state kinetic constants using purified enzymes. The mitotic RLC kinase is distinct from cdc2 kinase, protein kinase A and protein kinase G, as activators or inhibitors specific for these kinases do not affect the mitotic kinase activity. The activity of the mitotic RLC kinase is enhanced by the addition of Ca2+ and DAG and/or phorbol esters, characteristics of a conventional protein kinase C (PKC). Moreover, the PKC inhibitors, Go6983 and Go6976, significantly attenuate the phosphorylation of the RLC in mitotic extracts. Apparent steady-state kinetic studies indicate that several PKC isoforms display high specificity for myosin-II. These results suggest that current models describing Ser-1/2 phosphorylation during mitosis need to be re evaluated. PMID- 11763197 TI - Interfilament spacing, Ca2+ sensitivity, and Ca2+ binding in skinned bovine cardiac muscle. AB - The length-dependence of myofilament Ca2+ sensitivity in cardiac muscle appears to be a function of length-dependent variation in the lateral separation of actin and myosin filaments. The goal of this study was to determine how force, Ca2+ sensitivity, and Ca2+ binding to troponin C are correlated in skinned bovine ventricular muscle bundles set at sarcomere length 1.9 microm and subjected to varying degrees of osmotic compression with Dextran T-500. With 5, 10, and 15% Dextran T-500 the muscle diameter was reduced by 13, 21, and 25%, respectively. Addition of 5% Dextran T-500 caused increases in developed force, Ca2+ sensitivity, and in the affinity of Ca2+ for the regulatory binding site on troponin C. All of these parameters were reversed back toward control levels with 10% Dextran T-500. With 15% Dextran T-500 all parameters were decreased to below control levels. These data indicate that (1) there is an optimal filament separation at which both Ca2+ sensitivity and Ca2+ binding are maximized, and (2) Ca2+-troponin C affinity is linked to changes in Ca2+ sensitivity rather than to changes in interfilament spacing. PMID- 11763198 TI - Early and selective disappearance of telethonin protein from the sarcomere in neurogenic atrophy. AB - Mutations of the human telethonin gene have recently been shown to cause limb girdle muscular dystrophy type 2G in three Brazilian families. The mRNA has been shown to be dynamically regulated in animals, however, the fate of the protein in human muscle is unknown. In order to assess the expression of telethonin in more frequently encountered myopathological conditions we generated and characterized a rabbit antiserum raised against the C-terminal end of telethonin by immunoblotting and immunogold EM. Indirect immunofluorescence analysis of a wide variety of neuromuscular disorders including dystrophinopathies, metabolic myopathies, denervation disorders, congenital and inflammatory myopathies revealed that the characteristic Z-band staining of telethonin was preserved in all disease entities included in our study. However, a reduced telethonin immunoreactivity was observed in up to 10% of type II fibers in 10 cases of neurogenic atrophy. A decreased telethonin staining was more frequently observed in early stages of fiber atrophy than in type II fibers displaying normal or highly atrophic fiber diameters. Hence, not only the telethonin transcript is rapidly downregulated in denervated muscle but the protein itself undergoes dynamic changes while its known sarcomeric binding partner titin remains unaltered. Beyond its role as a static component of Z-bands, these findings indicate that telethonin protein levels seems to be at least in part regulated by neuronal activity and is thus linked to the dynamic control of myofibrillogenesis and muscle turnover in human skeletal muscle. PMID- 11763199 TI - Changes in mitochondrial Ca2+ detected with Rhod-2 in single frog and mouse skeletal muscle fibres during and after repeated tetanic contractions. AB - The present study investigated mitochondrial Ca2+ uptake and release in intact living skeletal muscle fibres subjected to bouts of repetitive activity. Confocal microscopy was used in conjunction with the Ca2+-sensitive dye Rhod-2 to monitor changes in mitochondrial Ca2+ in single Xenopus or mouse muscle fibres. A marked increase in the mitochondrial Ca2+ occurred in Xenopus fibres after 10 tetani applied at 4 s intervals. The mitochondrial Ca2+ continued to increase with increasing number of tetani. After the end of tetanic stimulation, mitochondrial Ca2+ declined to 50% of the maximal increase within 10 min and thereafter took up to 60 min to return to its original value. Depolarization of the mitochondria with FCCP greatly attenuated the rise in the mitochondrial Ca2+ evoked by repetitive tetanic stimulation. In addition, FCCP slowed the rate of decay of the tetanic Ca2+ transient which in turn led to an elevation of resting cytosolic Ca2+. Accumulation of Ca2+ in the mitochondria was accompanied by a modest mitochondrial depolarization. In contrast to the situation in Xenopus fibres, mitochondria in mouse toe muscle fibres did not show any change in the mitochondrial Ca2+ during repetitive stimulation and FCCP had no effect on the rate of decay of the tetanic Ca2+ transient. It is concluded that in Xenopus fibres, mitochondria play a role in the regulation of cytosolic Ca2+ and contribute to the relaxation of tetanic Ca2+ transients. In contrast to their important role in Xenopus fibres, mitochondria in mouse fast-twitch skeletal fibres play little role in Ca2+ homeostasis. PMID- 11763200 TI - Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres. AB - This study investigated the effects of the protein kinase A (PKA) inhibitor, H 89, in mechanically-skinned muscle fibres and intact muscle fibres, in order to determine whether PKA phosphorylation is essential for normal excitation contraction (E-C) coupling. In skinned EDL fibres of the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10 microM H 89, a concentration more than sufficient to fully inhibit PKA. Staurosporine (1 microM), a potent non-specific kinase inhibitor, also had little if any effect on depolarization-induced responses. At 1-2 microM, H-89 significantly slowed the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. With 100 microM H-89, the force response to depolarization by ion substitution was completely abolished. This inhibitory effect was reversed by washout of H-89 and was not due to block of the Ca2+ release channel in the sarcoplasmic reticulum (SR). In intact single fibres of the flexor digitorum longus (FDB) muscle of the mouse, 1-3 microM H-89 had no noticeable effect on action-potential-mediated Ca2+ transients. Higher concentrations (4-10 microM) caused Ca2+ transient failure in fibres stimulated at 20 Hz in a manner indicative of action-potential failure. At 10-100 microM, H 89 also inhibited net Ca2+ uptake by the SR and affected the Ca2+-sensitivity of the contractile apparatus in rat skinned fibres. All such effects were proportionately greater in toad muscle fibres. These results do not support the hypothesis that phosphorylation is essential for the Ca2+ release channel to open in response to voltage-sensor activation in skeletal muscle fibres. PMID- 11763201 TI - Overexpression of miniparamyosin causes muscle dysfunction and age-dependant myofibril degeneration in the indirect flight muscles of Drosophila melanogaster. AB - Miniparamyosin (mPM) is a protein of invertebrate muscle thick filaments. Its similarity to paramyosin (PM) suggests that it regulates thick filament and myofibril assembly. To determine its role in muscle structure and function we overexpressed mPM in muscles of Drosophila melanogaster. Surprisingly, myofibrils accumulating excess mPM assemble nearly normally, with thick filament electron density and sarcomere length unaffected. Myofibrils in some indirect flight muscle groups are misaligned and young flies exhibit a moderate level of flight impairment. This phenotype is exacerbated with age. Transgenic flies undergo progressive myofibril deterioration that increases flight muscle dysfunction. Our observations indicate that the correct stoichiometry of mPM is important for maintenance of myofibril integrity and for the proper function of the flight musculature. PMID- 11763202 TI - Do SF-36 summary component scores accurately summarize subscale scores? AB - Standard scoring algorithms were recently made available for aggregating scores from the eight SF-36 subscales in two distinct, higher-order summary scores: Physical Component Summary (PCS) and Mental Component Summary (MCS). Recent studies have suggested, however, that PCS and MCS scores are not independent and may in part be measuring the same constructs. The aims of this paper were to examine and illustrate (1) relationships between SF-36 subscale and PCS, MCS scores, (2) relationships between PCS and MCS scores, and (3) their implications for interpreting research findings. Simulation analyses were conducted to illustrate the contributions of various aspects of the scoring algorithm to potential discrepancies between subscale profile and summary component scores. Using the Swedish SF-36 normative database, correlation and regression analyses were performed to estimate the relationship between the two components, as well as the relative contributions of the subscales to the components. Discrepancies between subscale profile and component scores were identified and explained. Significant correlations (r = -0.74, -0.67) were found between PCS and MCS scores at their respective upper scoring intervals, indicating that the components are not independent. Regression analyses revealed that in these ranges PCS primarily measures aspects of mental health (57% of variance) and MCS measures physical health (65% of variance). Implications of the findings were discussed. It was concluded that the current PCS MCS scoring procedure inaccurately summarizes subscale profile scores and should therefore be revised. Until then, component scores should be interpreted with caution and only in combination with profile scores. PMID- 11763203 TI - Interpreting SF-36 summary health measures: a response. AB - In response to questions raised about the "accuracy" of SF-36 physical (PCS) and mental (MCS) component summary scores, particularly extremely high and low scores, we briefly comment on: how they were developed, how they are scored, the factor content of the eight SF-36 subscales, cross-tabulations between item-level responses and extreme summary scores, and published and new tests of their empirical validity. Published cross-tabulations between SF-36 items and PCS and MCS scores, reanalyses of public datasets (N = 5919), and preliminary results from the Medicare Health Outcomes Survey (HOS) (N = 172,314) yielded little or no evidence in support of Taft's hypothesis that extreme scores are an invalid artifact of some negative scoring weights. For example, in the HOS, those (N = 432) with "unexpected" PCS scores worse than 20 (which, according to Taft, indicate better mental health rather than worse physical health) were about 25% more likely to die within two years, in comparison with those scoring in the next highest (21-30) category. In this test and in all other empirical tests, results of predictions supported the validity of extreme PCS and MCS scores. We recommend against the interpretation of average differences smaller than one point in studies that seek to detect "false" measurement and we again repeat our 7-year old recommendation that results based on summary measures should be thoroughly compared with the SF-36 profile before drawing conclusions. To facilitate such comparisons, scoring utilities and user-friendly graphs for SF-36 profiles and physical and mental summary scores (both orthogonal and oblique scoring algorithms) have been made available on the Internet at www.sf-36.com/test. PMID- 11763204 TI - A gap approach to exploring quality of life in mental health. AB - Improving quality of life (QoL) is an important treatment outcome for the serious mentally ill. There is, however, a need for an instrument which both captures consumers own assessments and gives direct information for intervention. A useful approach is to define QoL as the gap between actual and ideal life circumstances, which is weighted by importance. In this paper we detail how we developed and evaluated a QoL instrument which follows this model. This instrument, the 'QoL GAP', is based on self-appraised items within various life domains. For each item respondents firstly identify what they have (actual) and then what they would like (ideal). They then rate the item for its importance and make any comments. A weighted gap score for each item is subsequently derived from the ideal actual gap being weighted by the importance rating. This weighted gap score is then related to domain satisfaction ratings, while their average from each domain is related to overall satisfaction and well-being. We surveyed 120 individuals with a serious and enduring mental illness living in different types of residences, such as psychiatric hospitals, hostels, or their own homes, in a largely urban part of Queensland. Sixty-eight percent were males, and 92% had schizophrenia or related disorders. We found that our approach demonstrated good psychometric properties, and that the model-based predictions were borne out: weighted gap measures were consistently more strongly related to domain satisfaction than were the actual circumstances alone. While further work is being undertaken--in such matters as short-forms and further evaluation of the QoL-GAP in a longitudinal study--our results suggest that this 'gap' approach helps consumers state their own goals and give their opinions and so is particularly relevant for consumer focused mental health delivery and research. PMID- 11763205 TI - Probabilities of transition among health states for older adults. AB - GOAL: To estimate the probabilities of transition among self-rated health states for older adults, and examine how they vary by age and sex. METHODS: We used self rated health (excellent, very good, good, fair, poor, dead) collected in two longitudinal studies of older adults (mean age 75) to estimate the probability of transition in 2 years. We used the estimates to project future health for selected cohorts. FINDINGS: These older adults were most likely to be in the same health state 2 years later, but a substantial proportion changed in both directions. Transition probabilities varied by initial health state, age and sex. Men were more likely than women to transition to excellent or dead. Women were more likely than men to transition to good or fair health. Although women aged 70 will have more years of life and more years of healthy life than men, they also have more years of unhealthy life, and the proportion of remaining life that is healthy is slightly higher for men. When observed and predicted years of healthy life (YHL) were compared in various subgroups, the YHL of persons with less favorable baseline characteristics was lower than predicted, and vice-versa. Differences, however, were small (about 5%). CONCLUSIONS: These transition probability estimates can be used to predict the future health of individuals or groups as a function of current age, sex, and self-rated health. PMID- 11763206 TI - Agreement between patients' and proxies' reports of quality of life in Alzheimer's disease. AB - Agreement between self reports and proxy reports of health-related quality of life (H RQoL) was examined in a sample of 76 patients with mild to moderate Alzheimer's disease and their proxies. Patients and proxies completed an '17-item Duke health profile'. The items were rephrased for the proxy. The proportion of exact agreement between patients and proxies on the 17 items ranged from 26.3 to 52.6%. Results reveal poor to moderate agreement (intraclass correlation coefficients (ICCs) from 0.00 to 0.61 for 10 subscales) between patients' and proxies' reports. Agreement was higher for measures of function that are directly observable (physical health, disability) and relatively poor for more subjective measures. Proxy reliability varied according to the relationship of the proxy to the index subject. Spouses and nurses agreed more closely with index subjects than did children or nurses' aides. Agreement decreased with increasing severity of dementia. Statistically significant differences in mean scores were noted for several dimensions, with proxies tending to rate the patients as having a lower quality of life than the patients themselves. This study indicates the importance of considering the information source of a patient's HRQoL. However, assessments by proxies should be used with caution. PMID- 11763207 TI - The use of life review to enhance quality of life of people living with AIDS: a feasibility study. AB - People living with AIDS (PLWA) are confronted with uncertainty and their own mortality at an earlier than expected age. Life review, an intervention that has the potential to increase life satisfaction in the elderly experiencing transition points in their lives, may have a similar effect when used with PLWA. Therefore, the purpose of this feasibility study was to explore the use of life review in a sample of 20 PLWA through a randomized controlled trial of its effectiveness in decreasing depressive symptoms and in increasing self esteem, quality of life, and purpose in life. Compared to the control group, the treatment group had an improved overall quality of life and self-esteem over 12 months, less depressive symptoms over 12 months, and a greater purpose in life at 3 months. The effects that were seen were mainly small to medium effects. The findings from this feasibility study suggest the potential value of life review to enhance quality of life, purpose in life, and self-esteem, and to decrease depressive symptoms in PLWA. Further research is needed with a larger sample and with other groups such as PLWA experiencing virologic failure. PMID- 11763208 TI - Psychometric evaluation of the 12-item Well-being Questionnaire for use with people with macular disease. AB - This paper reports the evaluation of a generic measure of psychological well being, the 12-item Well-being Questionnaire (W-BQ12), for use with people who have the chronic eye condition, macular disease (MD). The W-BQ12 was incorporated in a self-administered questionnaire which was completed by 1421 members of the Macular Disease Society (MD Society). Unforced factor analysis elicited the expected three factors representing constructs of positive well-being, energy and negative well-being. A forced single-factor solution supported use of the whole scale to measure total general well-being. High Cronbach's alpha coefficients demonstrated good internal consistency reliability in the entire scale (alpha = 0.87) and in subscales (alpha > 0.78). The factor structure matched that found in samples of people with diabetes for whom the W-BQ12 was first developed, indicating construct validity. Expected subgroup differences in the MD sample indicated significantly poorer well-being in women than in men and also in participants who were registered blind or partially sighted compared to those who were not registered. The W-BQ12 will be useful in measuring outcomes in rehabilitative and medical interventions and in researching factors affecting adjustment to MD. PMID- 11763209 TI - Keeping the focus. PMID- 11763210 TI - Can saltwater toxicity be predicted from freshwater data? AB - The regulation of substances discharged to estuarine and coastal environments relies upon data derived from ecotoxicity tests. Most such data are generated for freshwater rather than saltwater species. If freshwater toxicity data are related to saltwater toxic effects in a systematic and predictable way, the former can be used to predict the latter. This would have economic advantages due to a reduction in toxicity testing of saltwater species. If toxicity data are plotted as species sensitivity distributions, four theoretical relationships between freshwater and saltwater can be envisaged. Examples show that each one of these relationships is supported by empirical data. These examples show that although there is considerable potential for freshwater to saltwater prediction, species parity and representativeness need to be examined for each chemical substance to avoid bias. PMID- 11763211 TI - What's in a name? PMID- 11763212 TI - Trace contaminant concentrations in the Kara Sea and its adjacent rivers, Russia. AB - Trace organic (chlorinated pesticides, PCBs, PAHs and dioxins/furans) and trace metal concentrations were measured in surficial sediment and biological tissues (i.e., worms, crustaceans, bivalve molluscs, and fish livers) collected from the Russian Arctic. Total DDT, chlordane, PCB and PAH concentrations ranged from ND to 1.2, ND to <0.1, ND to 1.5 and <20-810 ng g(-1), respectively, in a suite of 40 surficial sediment samples from the Kara Sea and the adjacent Ob and Yenisey Rivers. High sedimentary concentrations of contaminants were found in the lower part of the Yenisey River below the salt wedge. Total dioxins/furans were analysed in a subset of 20 sediment samples and ranged from 1.4 to 410 pg g(-1). The highest trace organic contaminant concentrations were found in organisms, particularly fish livers. Concentrations as high as 89 ng g(-1) chlordane; 1010 ng g(-1) total DDTs; 460 ng g(-1) total PCBs; and 1110 ng g(-1) total PAH, were detected. A subset of 11 tissue samples was analysed for dioxins and furans with total concentrations ranging from 12 to 61 pg g(-1). Concentrations of many trace organic and metal contaminants in the Kara Sea appear to originate from riverine sources and atmospheric transport from more temperate areas. Most organic contaminant concentrations in sediments were low; however, contaminants are being concentrated in organisms and may pose a health hazard for inhabitants of coastal villages. PMID- 11763213 TI - Litter burial and exhumation: spatial and temporal distribution on a cobble pocket beach. AB - A cobble beach (-6 diameter to -8 diameter) located on the South Wales coastline, UK, was studied over a three-month winter period to assess litter input levels. After total beach litter clearance, six surveys were conducted at consecutive spring tides which involved marking of previously unrecorded litter. The beach was soon inundated with debris, predominantly plastic beverage containers. Some marked litter was found to disappear from the beach surface, re-emerging weeks later which suggests that the potential for litter burial has been underestimated in litter research. Higher wave energies between surveys coincided with higher levels of previously unseen litter. These new inputs consisted of sea borne and exhumed litter. Items larger than the surrounding cobbles were found to work their way back to the surface of the beach after burial, smaller items remained buried. Pits dug into the cobble ridge confirmed the burial of mainly small items. PMID- 11763214 TI - The effects of dredge-spoil dumping on a shallow water soft-sediment community in the Solitary Islands Marine Park, NSW, Australia. AB - In December 1999, 28,000 m3 of sediment was dredged from two sites within the harbour at Coffs Harbour, NSW. Dredging was carried out using a trailing suction hopper-dredge which transported the spoil to a shallow (6 m) site within the adjacent Solitary Islands Marine Park for disposal. Evaluation of the effects of the dredge-spoil dumping at the receiving site was conducted by taking replicated van Veen grab samples at the disposal site and at two control sites, before, immediately after, and three months after dumping. The results indicated that dredge-spoil dumping had no detectable effect on either the structure of the invertebrate community or the physical characteristics of sediment at the receiving site. Although there were some significant faunistic differences between samples from the disposal site and the control sites immediately following dumping, these were related to pre-existing differences between sites rather than to the effects of dredge-spoil disposal. Four principal factors are likely to have contributed to the lack of impact: (i) dredged material had similar sedimentary characteristics to those at the receiving site; (ii) dredged material was free from contaminants; (iii) the disposal method systematically distributed a number of shallow layers of sediment over the disposal site and thus motile macrofauna had the opportunity to migrate upwards between passes of the barge; and (iv) the disposal site was in a high energy environment where the resident biota are likely to be adapted to dynamic sedimentary conditions. The lack of detectable effects suggests that the disposal strategy was one which minimized impacts within an area which has high conservation value and should thus be adopted as a model for future works within the region. PMID- 11763215 TI - Comparative concentrations of metals in marine species from French Frigate Shoals, North Pacific Ocean. AB - Concentrations of arsenic, cadmium, chromium, copper, lead, mercury, selenium, and zinc were measured in coral, crab, eel, fish, lobster, and sediment samples collected from French Frigate Shoals, North Pacific Ocean. The sediments contained relatively high concentrations of selenium; moderate concentrations of arsenic, cadmium, copper and lead; and low concentrations of chromium and zinc. Metal concentrations were also determined in coral and crabs collected from the island of Oahu. Notably, a crab (Grapsus tenuicrustatus) and the undulated moray eel (Gymnothorax undulatus) exhibited high levels of copper and arsenic, respectively, relative to the other species studied. The concentrations of arsenic in the eel averaged 225 microg g(-1) dry wt, which was 3-12 times higher than that in all of the other species tested. The average concentration of copper in the crab was 343 microg g(-1) dry wt, 3-86 times greater than that in the other species studied. These data indicate background and comparative levels of the metals among the studied species. Lead levels in the coral (9-10 microg g(-1) dry wt) and crab (42-57 microg g(-1) dry wt) from Tern and Disappearing Islands were 23-283-fold greater than those from Oahu (0.4 and 0.2 microg g(-1) dry wt, respectively). PMID- 11763216 TI - Detection of anthropogenic Cu, Pb and Zn in continental shelf sediments off Sydney, Australia--a new approach using normalization with cobalt. AB - Concentrations of Co, Cu, Pb and Zn were determined in 107 surficial sediment samples from the continental margin adjacent to Sydney, Australia. The spatial distributions of trace metals in the sediments and the mud content are similar and increase with greater distance from the coast. In contrast, normalization of the concentrations of Cu, Pb and Zn in the total sediment with Co enables a coastal anthropogenic source to be identified. The spatial distribution of Co normalized concentrations of Cu, Pb and Zn in total sediment is similar to the distribution of these trace metals in the fine fraction of sediment (<62.5 microm), indicating that Co may be used as a normalizing element for determining contaminant sources in the marine environment near Sydney. PMID- 11763217 TI - Aliphatic and aromatic hydrocarbons in sediments of Santos and Cananeia, SP, Brazil. AB - Sediment samples from Santos and Cananeia, Sao Paulo Brazil were analysed by GC FID and GC-MS for aliphatic and aromatic hydrocarbons in order to gather information on the degree of contamination by oil and other biogenic contributions. Concentrations of total n-alkanes in Santos varied from 1.05 to 4.29 microg g(-1) and aromatic hydrocarbons from 0.08 to 42.39 microg g(-1). In Cananeia total n-alkanes varied from 4.37 to 157.90 microg g(-1). However, aromatic hydrocarbons were not detected. In Cananeia n-alkanes of terrestrial plants with high molecular weight predominate (n-C25, n-C27, n-C29, n-C31 and n C33). In Santos, a more uniform distribution of the n-alkanes and aromatic hydrocarbons was found at all the sediment stations. The hydrocarbon data from stations close to the Saboo Wharf, at Alemoa and in the COSIPA Channel revealed alarming levels of acenaphthylene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene and chrysene. PMID- 11763218 TI - Sources and geochemical constraints of polycyclic aromatic hydrocarbons (PAHs) in sediments and mussels of two Northern Irish Sea-loughs. AB - Polycyclic aromatic hydrocarbons (PAHs) were sampled from 30 sediment and 8 mussel (Mytilus edulis) stations in two Northern Irish Sea-toughs. Analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). Sedimentary organic carbon, % silt/clay and mean grain size were analysed in order to assess the role of geochemistry on PAH distribution. With the exception of two sites in Larne Lough representing localized regions of high contamination, sum(PAHs) in sediments ranged between 83 and 2300 ng g(-1). Regression analysis indicated that particle size and organic C were dominant factors in controlling the distribution of PAHs throughout the sediments. Sources of PAHs in both sea-loughs were dominated by pyrogenic inputs suggesting that diffuse sources such as atmospheric deposition may be a major source to both water bodies. The sum of PAHs in mussels ranged between 95 and 184 ng g(-1). Variations in concentrations may be explained by differences in the condition between mussel populations. Mussels in both sea loughs exhibit similar metabolic activities towards the PAH compounds which were predominantly bioaccumulated from sediments. PMID- 11763219 TI - The effects of freshwater flushing on marine heterotrophic protists--implications for ballast water management. AB - Survivorship of ballast-entrained marine heterotrophic protists was examined following freshwater flushing. The recovered taxa, including typical marine rhizopods such as Platyamoeba murchelanoi, Labyrinthula spp, Pontifex maximus, Thecamoeba orbis, and the ciliate Condylostoma arenarium, were reared in waters of various salinities. After 2 months, the original salinity subsample retained five protist taxa, the freshwater six, including the amoeba Cochliopodium bilimbosum, the brackish water 22 taxa, and the seawater 19 taxa. Since protists form a major component of marine microbial food webs, their survival may be instrumental in supporting complex ballast-entrained food webs. Our study raises questions as to the reliability of open-ocean exchange (OOE) or freshwater flushing as effective control measures. PMID- 11763220 TI - Variation of antioxidant enzyme activities of sprat (Sprattus sprattus) larvae and organic contaminant levels in mixed zooplankton from the southern North Sea. AB - Sprat (Sprattus sprattus) larvae and mixed zooplankton were collected from sites in the southern North Sea across three transects running north, north-west and west from the Elbe and Weser estuaries (Germany). Sprat larval sub-cellular fractions (13,500 g supernatants) were assayed for the antixoxidant enzymes catalase (EC 1.11.1.6) and superoxide dismutase (SOD; EC 1.15.1.1), and levels of polychlorobiphenyls (PCBs), p,p'-DDE and polycyclic aromatic hydrocarbons (PAHs) were determined in the mixed zooplankton (fish larval diet). Higher levels (p < 0.05) of SOD and catalase activities were observed at sites closest to estuaries corresponding to sites with the highest levels (p < 0.05) of total PCBs and p,p' DDE. Antioxidant enzymes activities decreased in samples collected from sites further from the estuaries across a northern and north-western transect; however this was not observed across a western transect. Larval antioxidant enzyme activities are discussed in relation to potential processes affecting them including plankton contaminant level distributions. PMID- 11763221 TI - Antibiotic resistant bacteria in fish from the Concepcion Bay, Chile. AB - Antibiotic resistant bacteria from commercial demersal and pelagic fish captured in the Concepcion Bay, Chile were investigated. Viable counts of antibiotic resistant bacteria isolated from gill and intestinal content samples showed high frequencies of resistance to ampicillin, streptomycin and tetracycline, while the proportion of chloramphenicol resistance was rather low. A high incidence of resistance to ampicillin, streptomycin, tetracycline and nitrofurantoin, as well as almost an absence of resistance to gentamicin, amikacin and cotrimoxazole was found among selected isolates which represented the resistant bacterial population. These strains mainly belonged to Vibrionaceae and Enterobacteriaceae and were predominantly resistant to 3 and 4 antibacterials. Isolates from demersal fish exhibited resistance to as many as 8-10 compounds, whereas those from pelagic fish were resistant to seven or fewer antibiotics. These results suggest that Chilean commercial fishes residing in waters near the disposals of urban sewage might play a role as carriers of antibiotic resistant bacteria prompting a health risk to public health for fish consumers. PMID- 11763222 TI - Effects of chromated copper arsenate (CCA) wood preservative on early fouling community formation. AB - The effects of the anti-marine-borer timber preservative CCA (a pressure impregnated solution of copper, chromium and arsenic compounds) on early fouling community formation were investigated during a number of field trials. The formation of a biofilm on the surface of CCA-treated and untreated timber panels of Scots pine was examined by scanning electron microscopy following submersion in Langstone Harbour, Portsmouth, UK for periods of 2, 7, 14 and 28 days. Results indicated a slightly faster rate of biofilm formation after 2 and 7 days of exposure on untreated timber compared to CCA-treated timber, although no differences were visible between panels after 14 and 28 days exposure, or between panels treated to different CCA loadings after all exposure periods. Settlement of the serpulid Ficopomatus enigmaticus and two species of barnacles (Elminius modestus and Balanus crenatus) onto the surface of untreated and CCA-treated panels of Scots pine was examined following 4 weeks exposure in a brackish water millpond at Emsworth, West Sussex. Numbers of individuals were higher on CCA treated panels than on untreated panels, and in the case of F. enigmaticus abundance of individuals increased with increasing preservative loadings. Early colonization by macroalgal species on the surface of CCA-treated and untreated panels of Scots pine was examined following submersion of panels in Langstone Harbour for a period of 4 weeks. Percentage cover of most species of algae was similar on the surface of CCA-treated and untreated panels, with the exception of Hincksia granulosa and Ceramium nodulosum which had significantly higher percentage cover on untreated panels. Possible explanations for the recruitment patterns are discussed. PMID- 11763223 TI - The effect of accidental sulphuric acid leaking on metal distributions in estuarine sediment of Patos Lagoon. AB - In August of 1998 the tanker BAHAMAS belonging to the Chem Oil Company containing 12,000 t of concentrated sulphuric acid, had an accident on board, after which estuarine water entered one of the compartments of the tanker, resulting in a vigorous exothermic reaction. The reaction of acid with the metallic interior hull of the ship and the accompanying heat and H2 production resulted in an imminent risk of explosion. To avoid an explosion, given the fact that neutralization was not possible, some of the cargo was discharged into the surrounding water. Neutralization was done in January 1999, after the acid concentration in the tanker had decreased and the concentrations of Fe, Cr and Ni remained elevated. Metal concentrations in bottom sediments showed significant modifications. Leached mercury migrated and redeposited downstream, reaching approximately 76 times the background values. Such an anomaly has a well expressed barrier character. The mechanism for redeposition of Hg and other metals probably followed the pattern: Downstream as a result of dilution and mixing with seawater the pH of acid-water increases, favouring adsorption and/or precipitation of metals. The leading edge of a geochemical barrier, at positions 7-9 of sampling sites (Fig. 1), is confirmed by pH variations in the water. The reestablishment of normal pH occurred after a short time due to the high buffering capacity of seawater and large natural dilution process. The concentration of metals in estuarine water during and after the accident showed insignificant anomalies. PMID- 11763224 TI - Developing a method to track oil and gas produced water discharges in estuarine systems using salinity as a conservative tracer. AB - Produced water is a high salinity by-product resulting from oil and gas production. Disposal methods include surface water discharge from a point source. The current field method used for fate and effect determinations in open water estuarine systems involves extending a compass oriented transect (COT) from the point source discharge--a method designed for a uniform offshore environment that might be inappropriate for the hydrologic and geomorphologic complexities found in estuarine systems. Research was conducted in a canal and a small, semi enclosed bay to observe effluent behaviour and to determine if salinity could be used to track the effluent. A salinity/conductivity/temperature (SCT) probe measured water properties within 1 cm of the sediment surface and identified a thin, bottom salinity plume that would have gone undetected by conventional instruments. The plume flowed across the sediment surface and towards greater depths. Plume-affected sampling stations exhibited higher levels of sediment contaminant indicators (SCIs) and indicated that station location could affect impact conclusions. PMID- 11763225 TI - Tributyltin along the coasts of Corsica (Western Mediterranean): a persistent problem. AB - Despite optimistic forecasts by various scientists after regulatory measures were taken in the 1980s, coastal tributyltin (TBT) contamination is still a major problem. The present study concerning Corsica (Western Mediterranean) shows that contamination is not limited to harbour areas, but extends along the coast, involving protected nature reserves. The concentrations measured in harbours, which can reach 200 ng TBT l(-1), tend to incriminate both pleasure craft and ferries providing regular service between the island and the continent. Contamination as high as 7 ng TBT l(-1) has been measured in waters of the Scandola nature reserve, which is quite excessive given the no effect concentrations (NOEC) for marine fauna are around 1-2 ng TBT l(-1). The inadequacy of current regulations and their application are a major factor in this situation. PMID- 11763226 TI - Oxygen, sulphide and nutrient uptake of the mangrove mud clam Anodontia edentula (Family: Lucinidae). AB - Oxygen, sulphide and nutrient (ammonia, nitrite and phosphate) uptake of Anodontia edentula was measured. Oxygen and sulphide were measured from sealed containers provided with 1 l fresh mangrove mud (sulphide source) and seawater (oxygen source) with two treatments (with and without clam) at 16 replicates each. Oxygen, sulphide and other parameters were measured at days 1 (initial), 3 and 5 (final). Nutrients were measured from containers filled with 1.5 l wastewater from a milkfish broodstock tank with two treatments (with and without clam) at eight replicates each. Ammonia, NO2 and P04 were measured at days 0 (initial) 3, 6, 9 and 12 (final). Results showed significantly decreasing oxygen and sulphide concentrations in treatment with clams (ANOVA, p < 0.001). A significantly higher ammonia concentration (ANOVA, p < 0.05) was observed in treatment with clams while no significant difference was observed in nitrite and phosphate between the two treatments. A decreasing ammonia and an increasing nitrite trend was also observed in both treatments starting at day 3. PMID- 11763227 TI - Distribution and partitioning of polycyclic aromatic hydrocarbons (PAHs) in different size fractions in sediments from Boston Harbor, United States. AB - The concentrations of 16 US EPA priority pollutant polycyclic aromatic hydrocarbons (PAHs) were analyzed in four size fractions (< 62, 62-125, 125-250, and > 250 microm) in three contaminated Boston Harbor sediments. Total PAH concentrations ranged from 7.3 to 358 microg/g dry wt. and varied largely among the different size fractions in these sediments. For all three sites, the highest PAH concentrations were associated with the large size (> 250 microm) fractions while the fine silt and clay fractions (< 62 microm) contained relatively low PAHs. Despite the great concentration differences, the composition of PAHs in the four size fractions of these sediments showed similar patterns dominated by PAHs with three or more rings. By examining the distribution patterns of selected alkyl homologs to parent compounds, the results indicate that the major PAHs contributing to the high contamination in the inner harbor sediments were from pyrogenic sources. A positive correlation between PAHs and sedimentary organic carbon exists for all size fractions in the sediments. Calculated organic carbon normalized partition coefficients (log K(oc)) for selected major PAHs indicate near-equilibrium partitioning of PAHs among the different size fractions despite their large concentration variations. Sedimentary organic matter associated with different size fractions was the controlling factor for the observed distribution differences of PAHs among the size fractions. Our results also suggest that sedimentary organic matter with different origins and maturities may have somewhat different PAH sorption characteristics. Particulate organic matter of charcoal, plant detritus and Capitella fecal pellets in the sediments appear to sorb PAHs more strongly than organic matter associated with clay minerals. The strong association of PAHs with these organic particles in sediments will have a great influence not only on their distribution but also on long-term environmental impact. PMID- 11763228 TI - Effect of sampling frequency on shoreline microbiology assessments. AB - More than 80,000 shoreline bacteriological samples are collected annually in southern California to protect beachgoer health, but sampling frequency varies from daily to monthly among sampling sites. To assess the effectiveness of various sampling frequencies, we used five years of data from 24 Los Angeles area sites that have been monitored daily to simulate five alternative sampling strategies: five weekdays, five days per week including a weekend day, three days per week, weekly, and monthly. For each of these sampling strategies, we included in the simulation the local custom of adaptive sampling, in which a site is resampled the following day if bacterial concentrations exceed the State of California's beach water quality standards. We found that sampling five times per week resulted in observing about 80% of the events in which State standards were exceeded. This frequency dropped to 55%, 25%, and 5% for three times per week, weekly, and monthly sampling, respectively. Adaptive sampling was ineffective because nearly 70% of the water quality exceedences were single-day events, even at the most frequently contaminated sites. This high frequency of single-day events is of concern because the public is typically notified about water quality conditions 24-48 h after samples are collected, meaning that most warnings are out-of-date when they are issued. PMID- 11763229 TI - Public perceptions of environmental quality: a survey study of beach use and perceptions in Los Angeles County. AB - Despite documented successes in the battle to clean up the coastal waters of Southern California, Los Angeles County residents continue to view the ocean more as a place of pollution than a vibrant and healthy place for bathing and swimming. This study shows that residents of Los Angeles County tend to hold perceptions of marine water quality that are at odds with data on bacteriological measures of water quality collected by local sanitation districts (and reported by not-for-profit Heal the Bay). Summary results of a survey of 400 randomly chosen households in Los Angeles County are given. Respondents were asked about their beach use and perceptions of environmental quality: both coastal water quality and air quality. The results suggest that perceptions of coastal water quality may be influenced less by "current coastal education campaigns" and more by the media and other factors. PMID- 11763230 TI - The interpretation of body trace metal concentrations in neogastropods from Hong Kong. AB - Three species of neogastropods, i.e., Thais clavigera, Thais luteostoma and Morula musiva, were collected from 12 sites in the coastal waters of Hong Kong, including clean and known metal-enriched ones. Accordingly, body trace metal concentrations varied greatly. Copper and zinc body concentrations compared poorly with those of accepted biomonitors and presumed metal contamination profiles. Much is known about the feeding ecology of neogastropods on local shores and where direct observational data were not available, their diets could, nevertheless, be estimated reliably. Accumulated metal concentrations can be interpreted with regard to dietary history. T. luteostoma, for example, had body copper concentrations of 51.8 microg g(-1) on an exposed shore and a diet of mainly barnacles. In contrast, on a sheltered shore (but only some 250 m distant) where the diet consisted mainly of oysters, body copper concentrations were approximately 15 times greater at 833 microg g(-1). Similar results were obtained for T. clavigera. The results of this analysis suggest that neogastropods can play a significant role in trace metal trophic transfer studies, especially as their representatives are intertidally and subtidally ubiquitous and can be spatially separated into tropical specialists and temperate generalists. PMID- 11763231 TI - A statistical riverine litter propagation model. AB - A statistical riverine litter propagation (RLP) model based on importance sampling Monte Carlo (ISMC) simulation was developed in order to predict the frequency distribution of certain litter types in river reaches. The model was preliminarily calibrated for plastic sheeting by a pilot study conducted on the River Taff, Wales (UK). Litter movement was predominantly controlled by reach characteristics, such as vegetation overhang and water-course obstructions. These affects were modeled in the simulations, by utilizing geometric distributions of river reaches in the time domain. The proposed model satisfactorily simulated the dosing experiments performed at the River Taff. It was concluded from the preliminary calibrations that, the RLP model can be efficiently utilized to portray litter propagation at any arbitrarily selected river site, provided that the stream flows and reach characteristics are calibrated by representative probability distributions of similar sections. Therefore, the RLP model can be considered as a new statistical technique that can predict litter propagation in river sections. PMID- 11763232 TI - Standing stock and production rate of phytoplankton and a red tide outbreak in a heavily eutrophic embayment, Dokai Bay, Japan. AB - The seasonal variation of phytoplankton biomass and primary productivity in a heavily eutrophic embayment, Dokai Bay, Japan, was determined. Dokai Bay was characterized by high phytoplankton biomass and productivity during summer and low phytoplankton biomass and productivity during other seasons. The results suggested that phytoplankton growth was limited by only irradiance and water temperature under the high nutrient concentrations available for phytoplankton growth in the entire year. Moreover, in spite of sufficient nutrient for phytoplankton growth in the entire year, a red tide occurred only in the summer period in this bay. Our results suggested that a red tide occurred by the high phytoplankton growth rate in the summer season, but in other periods surface phytoplankton was flushed out of the bay before forming the red tide, because phytoplankton growth rate was low and could not form the red tide due to low irradiance and low water temperature. PMID- 11763233 TI - Nutrients, trace metals, and organic contaminants in Banten Bay, Indonesia. PMID- 11763234 TI - Metallic elements and metal poisoning among white-tailed sea eagles from the Baltic south coast. PMID- 11763235 TI - Plastic ingestion by a leatherback turtle Dermochelys coriacea from the Azores (NE Atlantic). PMID- 11763236 TI - Smart behavior of true slime mold in a labyrinth. AB - Even for humans it is not easy to solve a maze. But the plasmodium of true slime mold, an amoeba-like unicellular organism, has shown an amazing ability to do so. This implies that an algorithm and a high computing capacity are included in the unicellular organism. In this report, we discuss information processing in the microorganism to focus on the issue as to whether the maze-solving behavior is akin to primitive intelligence. PMID- 11763237 TI - Sure facts and open questions about the origin and evolution of photosynthetic plastids. AB - Some eukaryotic groups carry out photosynthesis thanks to plastids, which are endosymbiotic organelles derived from cyanobacteria. Increasing evidence suggests that the plastids from green plants, red algae, and glaucophytes arose directly from a single common primary symbiotic event between a cyanobacterium and a phagotrophic eukaryotic host. They are therefore known as primary plastids. All other lineages of photosynthetic eukaryotes seem to have acquired their plastids by secondary or tertiary endosymbioses, which are established between eukaryotic algae, already containing plastids, and other eukaryotic hosts. Both primary and secondary symbioses have been followed by extensive plastid genome reduction through gene loss and gene transfer to the host nucleus. All this makes the reconstruction of the evolutionary history of plastids a very complex task, indissoluble from the resolution of the general phylogeny of eukaryotes. PMID- 11763238 TI - Expression of Neisseria gonorrhoeae cell division genes ftsZ, ftsE and minD is influenced by environmental conditions. AB - The activity of the promoter regions of the cell division genes ftsZ, ftsE, minC, minD and minE from Neisseria gonorrhoeae (Ng) was studied under different environmental conditions using lacZ translational fusions. The promoters of the minNg genes have not been previously determined and we identified promoter regions upstream of each gene (minCp, minDp and minEp). We determined that minDp had the strongest activity. Expression of the promoter regions of ftSZ(Ng) and ftsE(Ng), which we had previously identified, as well as minD(Ng), were then studied under conditions reflecting the environment of the genitourinary tract. These conditions included anaerobiosis, presence of isoleucine or urea (3 mM and 400 mM, respectively) and acidity of pH 6. Both beta-galactosidase expression and northern blot analysis indicated that all three genes were upregulated under anaerobiosis. The addition of isoleucine as well as media at pH 6 did not have any significant effects on the promoter activity of these genes while the presence of urea significantly decreased ftsZ(Ng) promoter activity. The expression of the minD(Ng) promoter region was analyzed during different growth phases and shown to follow the growth behavior of the culture. By contrast, the ftSZ(Ng) promoter activity continued to rise after the onset of the stationary phase. When gonococcal ftsZ promoter 1, (Pz1) was altered by site-directed mutagenesis, a significant decrease in the expression of ftsZ(Ng) was observed under both aerobic and anaerobic conditions. These data infer that gonococci regulate their cell division in response to different environments. PMID- 11763239 TI - Effect of O2, H2 and redox potential on the activity and synthesis of hydrogenase 2 in Escherichia coli. AB - The aim of this work was to study the influence of O2 with special emphasis on low oxygen tension, the effect of H2 under various conditions of oxygen tension and the influence of the redox potential in the growth medium on hydrogenase 2 of Escherichia coli. The hydrogenase activity and the content of the large (HybC) and small (HybO) subunits of hydrogenase 2 were compared during turbidostat cultivation in a wild strain and mutant HDK103 lacking hydrogenases 1 and 3. No hydrogenase 2 activity in the mutant HDK103 was observed under aerobic conditions, but it was maximal under anaerobic conditions and half-maximal at an oxygen tension of approximately 4 mbar as is common for enzymes of anaerobic respiration. The content of hydrogenase 2 in both the strains was maximal under anaerobic conditions. In the wild strain, H2 addition enhanced hydrogenase activity and the HybO content under microaerobic conditions only. Under anaerobic conditions endogenous H2 production hindered this effect. Under aerobic conditions, the 02-related negative effect seemed to dominate over the H2-related positive effect. By contrast, in the mutant HDK103, hydrogen influenced neither hydrogenase 2 activity nor its content. A possible role of hydrogenase I in the response of hydrogenase 2 to hydrogen is discussed. Under conditions of different O2 tension, hydrogenase activity in both strains correlated inversely with the value of the redox potential of the medium. The presence of H2 changed this dependence. Thus, the value of the redox potential itself is not a controlling factor for hydrogenase 2. PMID- 11763240 TI - In-frame fusion of a His-Cys motif into the Pseudomonas aeruginosa outer membrane OprI lipoprotein results in increased metal binding capacity by Escherichia coli. AB - OprI, a small outer membrane lipoprotein from Pseudomonas aeruginosa, can be produced in large amounts and anchored at the surface on Escherichia coli cells. A four-time repeated (His-Cys) motif was fused to the C-terminal part of OprI. After induction, E. coli cells harbouring the recombinant oprI gene became more sensitive to Cd and Co. The same cells, after IPTG induction, bound four to eight times more Cd and Cr than control cells expressing oprI alone. PMID- 11763241 TI - A sequence variant of Staphylococcus hominis with a high prevalence of oxacillin and fluoroquinolone resistance. AB - A newly identified subspecies of Staphylococcus hominis, S. hominis subsp. novobiosepticus, was found to be the cause of several invasive infections at a hospital in New Jersey. This subspecies differs from classical S. hominis, now S. hominis subsp. hominis, by the phenotypic characteristics of novobiocin resistance and the inability to ferment trehalose. DNA sequences of segments of 16S rRNA, DNA gyrase (gyrA), and DNA topoisomerase IV (grlA) genes were determined for the type strains of the 2 subspecies, and for 34 S. hominis clinical isolates. The 16S rRNA sequences of the type strains differed at 3 positions over 410 bp; the grlA sequences differed at 6 positions over 119 bp. These sequence differences define S. hominis subsp. novobiosepticus and S. hominis subsp. hominis "sequevars." Of 34 S. hominis clinical isolates, 31 were S. hominis subsp. novobiosepticus sequevars, 28 of which were resistant to both oxacillin and ciprofloxacin. The clinical microbiology laboratory, using a MicroScan system, identified 7 of the 31S. hominis subsp. novobiosepticus sequevars as S. hominis subsp. hominis on the basis of phenotypic characteristics. Three S. hominis subsp. hominis sequevars were all identified phenotypically as S. hominis subsp. hominis and were oxacillin- and ciprofloxacin susceptible. Although the precise relationship between the S. hominis sequevars and their phenotypic subspecies remains to be determined, our results indicate that antibiotic-resistant clinical isolates of S. hominis belong almost exclusively to the S. hominis subsp. novobiosepticus sequevar. PMID- 11763242 TI - Mercury resistance transposons of gram-negative environmental bacteria and their classification. AB - A total of 29 mercury resistance transposons were isolated from mercury-resistant environmental strains of proteobacteria collected in different parts of Eurasia and the USA and tested for hybridization with probes specific for transposase genes of known mercury resistance transposons. 9 were related to Tn21 in this test, 12 were related to Tn5053, 4 to Tn5041 and 1 to Tn5044; three transposons were negative in this test. Restriction mapping and DNA sequencing revealed that 12 transposons were identical or nearly identical to their corresponding relatives while the rest showed varying divergence from their closest relatives. Most of these previously unknown transposons apparently arose as a result of homologous or site-specific recombination. One of these, Tn5046, was completely sequenced, and shown to be a chimera with the mer operon and the transposition module derived from the transposons related to Tn5041 and to Tn5044, respectively. Transposon Tn5070, showing no hybridization with the specific probes used in this study, was also completely sequenced. The transposition module of Tn5070 was most closely related to that of Tn3 while the mer operon was most closely related to that of plasmid pMERPH. The merR of Tn5070 is transcribed in the same direction as the mer structural genes, which is typical for mer operons of gram-positive bacteria. Our data suggest that environmental bacteria may harbor many not yet recognized mercury resistance transposons and warrant their further inventory. PMID- 11763243 TI - Using inactivated microbial biomass as fertilizer: the fate of antibiotic resistance genes in the environment. AB - The waste product produced by Novo Nordisk A/S from microbial fermentations is used as agricultural fertilizer in Denmark (NovoGro) after being treated by heat and chemicals to destroy the microorganisms. The fertilizer contains DNA fragments from the genetically modified microorganisms used in industrial production. This DNA contains genes coding for the desired industrial products as well as genes used as genetic selection markers during production strain development. The antibiotic resistance markers used as genetic selection markers are chloramphenicol (Cm), kanamycin (Km) and ampicillin (Ap). The aim of the present study was to examine whether DNA and intact genes were present in NovoGro and whether horizontal transfer of DNA isolated from inactivated production strains occurred either in the laboratory or in the fields treated with NovoGro. DNA isolated from NovoGro was analysed by PCR and intact genes coding for a protease and chloramphenicol resistance were amplified. This isolated DNA was used for in vitro experiments including electroporation and transformation but no transfer of DNA to Escherichia coli or Bacillus subtilis was observed. The antibiotic resistance profile of the indigenous bacterial population in the fields treated with NovoGro compared with fields treated with inorganic fertilizers showed no differences. In addition, DNA isolated directly from the fields treated with NovoGro for up to 7 years was analysed by PCR and no specific production gene constructs could be detected. PMID- 11763244 TI - Measuring quality of life in women with vertebral fractures due to osteoporosis: a comparison of the OQLQ and QUALEFFO. AB - INTRODUCTION: Studies comparing the performance of health-related quality of life instruments in osteoporosis are lacking. We compared the feasibility, validity and reliability of the osteoporosis quality of life questionnaire (OQLQ) and the QUALEFFO (test version) in women with vertebral deformities due to osteoporosis. METHODS: Three hundred and thirty-eight patients diagnosed with primary osteoporosis and vertebral deformity and a random sample of 304 women from the general population (control group) were recruited. Patients and controls were randomly assigned to receive either the OQLQ or the QUALEFFO, and the SF-36 and EQ-5D. Test-retest reliability was assessed in the patient group. RESULTS: The QUALEFFO had more items with missing data and took slightly longer to administer (20.7 vs. 18.7 min). Cronbach's alpha and intraclass correlation coefficient (ICC) values for OQLQ domains (alpha: 0.75-0.91; ICC: 0.85-0.93) were slightly higher than for the QUALEFFO (alpha: 0.63-0.90; and ICC: 0.80-0.93). OQLQ and QUALEFFO domain scores correlated as expected with SF-36 and EQ-5D domains. Both questionnaires discriminated between patients and controls though the OQLQ showed slightly better discriminant power. DISCUSSION: The superior performance of the OQLQ in terms of administration time, missing responses, and discriminatory capacity needs to be weighed against the advantages of using a self-administered instrument such as the QUALEFFO. A full comparison also requires data on sensitivity to change. PMID- 11763245 TI - A psychometric analysis of the Quality of Life-Cancer Survivors (QOL-CS) in survivors of childhood cancer. AB - Given the increasing interest in quality of life research in cancer survivorship, psychometric properties of the Quality of Life-Cancer Survivors (QOL-CS) were explored in a group of childhood cancer survivors. The QOL-CS is a 41-item visual analog scale composed of four multi-item sub-scales (physical well-being, psychological well-being, social well-being, spiritual well-being) and two sub components (fears, distress). This instrument was incorporated in a mailed survey completed by 177 respondents. The underlying factor structure and internal reliability of the instrument were explored. A preliminary assessment of the external validity of the factor structure was undertaken. Results of a factor analysis were theoretically consistent with elements assessed in the QOL-CS, although misclassification of several items was noted and discussed. Internal consistency reliability was very good (Cronbach's alpha = 0.80-0.89) for five of the six factors. Moderate (0.30 < r < 0.45) to high (r > 0.60) concurrent validity was observed for four factors. Discriminant validity was noted across groups defined by health and social status variables. Psychometric analysis indicated that the instrument measured distinct and relevant domains of quality of life for childhood cancer survivors, but in its current form does not appear to be an optimal measure of quality of life in this population. PMID- 11763246 TI - Sleep problems, health-related quality of life, work functioning and health care utilization among the chronically ill. AB - OBJECTIVES: To provide a comprehensive assessment of whether sleep problems among the chronically ill are associated with decrements in functional health and well being, decreases in work functioning and increases in the use of health care services. DESIGN: Cross-sectional survey of patients from the Medical Outcomes Study (MOS), an observational study of functional health and well-being. Chronically ill patients (n = 3484) were sampled from health maintenance organizations, large multi-specialty groups, and solo or single-specialty group practices in Boston, Los Angeles, and Chicago. Chronic illness subgroups include: clinical depression (n = 527), congestive heart failure (229), diabetes (n = 577), recent myocardial infarction (n = 170), hypertension (n = 2206), asthma (n = 84), back problems (n = 771), and arthritis (n = 672). ANCOVA analyses of the relationship between sleep problems and SF-36 scales and summaries were performed. In addition, a 'relative impact' analysis determined what scales or summaries were most associated with sleep problems. MAIN OUTCOME MEASURES: Eight scales and two summary measures from the SF-36 Health Survey, work productivity and work quality measures and self-reports of health care utilization. RESULTS: Comparing chronically ill patients with no sleep problems to those with mild, moderate, or severe sleep problems revealed a direct association between sleep problems and decrements in health-related quality of life (HRQOL) as measured by SF-36 scales and summaries (MANOVA F 24.1; d.f. 24; p < or = 0.0001). In addition, significant differences in HRQOL were found when comparing patients with and without sleep problems within most of the disease groups studied. The relative impact analysis revealed that measures of mental health and the mental health summary were most associated with sleep problem severity in the total sample and chronic disease subsets, in comparison with measures of physical health. In addition, monotonic relationships were found between severity of sleep problems and decreases in work productivity and increases in health care utilization, as expected. CONCLUSIONS: The analyses revealed that sleep problems go hand in hand with poorer mental health, diminished work productivity and work quality and greater use of health care services. Sleep problems, therefore, may be a significant confounding factor in the interpretation of health outcomes among patients with chronic diseases. PMID- 11763247 TI - Can parents rate their child's health-related quality of life? Results of a systematic review. AB - A systematic review was conducted to determine the relationship between ratings of children's health-related quality of life (HRQoL) made by parents and children. This was investigated in relation to four questions: is agreement greater for some domains (e.g. physical HRQoL) than others?; do parents perceive illness to have a greater impact than their child?; how is agreement affected by child age, gender and illness status?; and is the relationship between proxy ratings affected by the method of data collection? Fourteen studies were identified. Consistent with previous research, there was greater agreement for observable functioning (e.g. physical HRQoL), and less for non-observable functioning (e.g. emotional or social HRQoL). Three studies assessed whether parents perceive the illness to have a greater impact than their child, but no clear conclusions could be drawn given differences in measures used. Agreement is better between parents and chronically sick children compared with parents and their healthy children, but no effects were found for age or gender. All of these results may be dependent on the specific measure of HRQoL employed. There remain strong arguments for obtaining information from both parents and children whenever possible. PMID- 11763248 TI - Efficacy results and quality-of-life measures in men receiving sildenafil citrate for the treatment of erectile dysfunction. AB - The aim of the present study was to evaluate the efficacy of sildenafil citrate and its effects on quality of life (QoL) in men with erectile dysfunction (ED) using data from three multicenter, double-blind, placebo-controlled clinical trials. Efficacy was evaluated using a global efficacy question (improvement of erections) and questions from the International Index of Erectile Function (IIEF) addressing the ability to achieve and maintain erections. QoL directly related to ED was evaluated using questions 13 and 14 of the IIEF, several psychometric instruments, and a questionnaire addressing men's concerns about their erection problems. Seventy-nine [corrected] percent of patients receiving sildenafil reported improved erections compared with 23% of patients receiving placebo (p < 0.0001); also reported were improvements in the ability to achieve and maintain erections with sildenafil but not with placebo (p < 0.0001). Improvements were also seen for other aspects of sexual function (overall satisfaction with sex life, sexual relationships with partners, concerns about erectile problems, p < 0.0001) and general mental health (well-being, self-control, satisfaction with relationship, health relative to 1 year ago, mental health; p < or = 0.05) following treatment with sildenafil. Thus, treatment of ED with sildenafil can significantly improve key QoL parameters related to sexual dysfunction and general mental health. PMID- 11763249 TI - Quality of Life (QoL) in severely disabled multiple sclerosis patients: comparison of three QoL measures using multidimensional scaling. AB - This study reports a comparison of three quality of life (QoL) measures completed by patients with advanced multiple sclerosis. Multidimensional scaling analysis explored the structure of relationships amongst a general health measure (the Short Form 36--SF 36) and two person-centred measures (the Patient Generated Index--PGI; and the Schedule for the Evaluation of Individual Quality of Life Direct Weighting version--SEIQoL-DW). Results showed distinct differences both between the two person-centred measures, and when compared against the general health measure, reflecting the different conceptual bases of these measures. The findings suggest that PGI scores closely relate to measures of physical functioning, whereas SEIQoL-DW scores relate more closely to feelings of health and vitality. The implications of these results for selection and development of appropriate QoL scales for the target population are discussed. PMID- 11763250 TI - Self-care agency and quality of life among adults diagnosed with inflammatory bowel disease. AB - Individuals with inflammatory bowel disease (IBD) often exhibit anxiety and depression, pain and reduced energy but may not adequately develop self-care agency (SCA) to manage IBD. The purpose of this study was to examine whether SCA is related to quality of life in adults diagnosed with IBD. The sample of 34 individuals for this descriptive, correlational study completed three questionnaires including the Appraisal of self-care agency scale (A.S.A.-A Scale), the Inflammatory bowel disease questionnaire and a Demographic data questionnaire. Results indicated SCA was unrelated to indicators of quality of life among IBD individuals. This finding may be attributed to the high level of functioning of the sample. However, IBD quality of life (emotional functioning, social functioning, and bowel and systemic symptoms) was negatively correlated with the number of medications individuals took and positively correlated with the number of diagnosed chronic illnesses. PMID- 11763251 TI - Research or stagnation? An AOF challenge. PMID- 11763252 TI - Effects of contact lens-induced hypoxia on the physiology of the corneal endothelium. AB - Contact lens wear can cause a number of physiological changes in the cornea. Two areas of interest in my laboratory have been contact lens effects on the endothelium and, more recently, the role of metabolic activity in predicting corneal swelling. The first part of this review focuses on the function of the corneal endothelium, the nature of its fluid pump, and the effects of contact lens-induced hypoxia and corneal pH changes on corneal endothelial function. In the second part, the etiology of hypoxia-induced corneal swelling is reviewed in relation to new studies on the causes of intersubject corneal swelling variability. The results indicate that corneal swelling is influenced by both corneal metabolic activity and endothelial function. PMID- 11763253 TI - Variations in accommodation and convergence responses in a minimally controlled photorefractive setting. AB - PURPOSE: A remote haploscopic photorefractor, designed for assessment of accommodation and convergence in infants and clinical groups, was used to determine heterophoria accommodative convergence/accommodation (AC/A) ratios in normal naive adults. These were compared with conventional clinical measures. METHODS: Twenty-one naive subjects were used to compare occluded and unoccluded prism cover test responses with the remote haploscopic photorefractor using a text and picture target. RESULTS: Although luminance was generally low for both targets, binocular vergences were appropriate for target demand in both studies. Binocular accommodation showed greater lag for the highest target accommodative demand and the less demanding target. Occlusion not only reduced vergence response, but also frequently caused a marked reduction in accommodation, especially to the picture target. Normal mean AC/A values were found, but with wide variations between individual subjects. CONCLUSIONS: Although mean accommodation, vergence, and AC/A values were comparable with published data, we suggest that in these conditions using naive subjects, accommodation is frequently inaccurate, especially on occlusion, without concomitant loss of vergence, at least at low light levels. Accommodative convergence may play a less important part in, and other cues contribute more to, the near reflex than has been previously suggested. PMID- 11763254 TI - Fractal analysis of eye movements during reading. AB - We present a new method for the analysis of reading eye movements based on the methods of nonlinear dynamics. In this preliminary study, the eye movements of normal and abnormal readers were analyzed for evidence of chaotic, nonlinear dynamical behavior. Both power spectral density analysis and fractal dimension determination showed evidence of nonlinearity as manifest in chaotic behavior. The computed fractal dimension of the system's presumed attractor seemed directly related to qualitative assessment of reading ability. Representative subjects did not differ in a similar analysis of pursuit movements. Although fractal analysis did not distinguish unconditionally between normal and abnormal reading in this preliminary study, it nevertheless offers a promising hitherto unused approach to the analysis of eye movements and the modeling of oculomotor behavior. PMID- 11763255 TI - The effect of saccades and brief fusional stimuli on phoria adaptation. AB - PURPOSE: The purpose of this experiment was to determine whether brief fusional stimuli and saccades similar to those seen in the alternate cover test affect phoria disadaptation. METHODS: Three cover test conditions were performed randomly. Before each test condition, subjects fused for 2 min at an angle convergent to the subjective phoria. In one test condition, subjects viewed monocularly. In another condition, subjects alternately fixated with each eye (no binocular time). In a third condition, subjects alternately fixated with each eye, and there was a 100-ms period of binocular viewing between alternations. The ocular vergence angle was monitored using scleral search coils. RESULTS: Vergence angle was plotted against time for each condition. The area under this plot was determined using a computer program. The area reflected the rate at which ocular vergence returned to the original phoria position. The mean area for the monocular condition was 300.9, the mean area for alternate fixation with no binocular time was 300.3, and the mean area for alternate fixation with binocular time was 205.2. CONCLUSIONS: Saccadic alternations do not affect phoria adaptation. However, short periods in which binocular disparate images are viewed significantly increase the rate at which phoria adaptation declines for some subjects. PMID- 11763256 TI - Comparing optical systems, and the concept of the converter system. AB - The purpose of this article was to present a complete and general method for comparing the first-order optical character of optical systems. The method provides a common basis for quantifying the difference between systems of all kinds including thin lenses, ophthalmic prisms, eyes before and after accommodation, eyes before and after refractive surgery, etc. Systems may be astigmatic or stigmatic, coaxial or noncoaxial. In special cases, the method reduces to being equivalent in essence to ostensibly incommensurate comparisons implicit or explicit in current optometric and ophthalmological usage (difference in power for refractions, corneas, and thin lenses, difference in prismatic power for prisms, ratio of magnifications for afocal telescopes, etc.). The method uses the concept of a converter system that when placed in front of or behind one system, converts its first-order optical character to the equivalent of a second system. Equations are presented for the ray transferences of the anterior and posterior converter systems for pair-wise comparisons in general. For any two systems, the transferences of the converter systems always exist and are unique. Numerical examples are presented; they illustrate converter systems that may be thin in special cases but thick otherwise. The transference of a converter system embodies and quantifies the optical difference between systems or characterizes the change from one state of a system (presurgical or preaccommodative, for example) to another (postsurgical or postaccommodative). The method provides a rational and uniform methodology for research and clinical applications in many areas of optometry and ophthalmology. PMID- 11763257 TI - Does meaning matter? The impact of word knowledge on lateral masking. AB - BACKGROUND: Many older adults have lost the use of their foveae due to disease. Because of this, they must use peripheral retina to do tasks formerly done using the fovea, such as letter identification and reading. Several researchers have recently proposed that reading in the periphery is limited by lateral masking: the reduced perceptibility of a target when it is surrounded by flanking stimuli. None of these studies tested the perceptibility of letters within words, where the semantic relationship between the target letter and the flanking letters is likely to improve perceptibility. This study sought to determine whether the semantic relationship between the flanking stimuli and the target stimulus affects perceptibility of letters in the periphery. METHODS: Young, normally sighted observers identified single letters and the middle letters of three letter words, trigrams, and letters flanked by x's (xax) presented for 150 ms at 10 degrees eccentricity on each of the primary meridia. In the first experiment, subjects identified letters presented alone and letters flanked by one x on either side. In the second experiment, subjects identified the middle letters of words, trigrams, and xax stimuli, which were either presented in blocks or randomly. In the third experiment, only the words and trigrams were used, and subjects were required to both identify the middle letter and simultaneously indicate whether the stimulus was a word or a trigram. RESULTS: The first experiment showed that single letters were identified about 50% more accurately than letters flanked by x's. In the second and third experiments, letter identification was better when the target and flanking letters formed a word than when they formed a trigram and better along the horizontal meridian than along the vertical meridian, which is consistent with previous studies. In the third experiment, the subject's ability to identify the stimulus type had a significant impact on performance. When the stimuli were words, subjects identified the middle letter on 87% of trials when they correctly identified the stimulus and 40% of the trials when they did not; for the trigrams these percentages were 65% and 5%. CONCLUSIONS: When the flanking letters and the target letter formed a word, observers were better able to identify the target than when they did not form a word, and this pattern was mediated by the observers' knowledge of stimulus type. These data suggest that to draw conclusions regarding the impact of lateral masking on reading, the stimuli used should be words, not random letter strings or other target/flanker combinations. PMID- 11763258 TI - Clinical measurement, artifact, and data analysis in dioptric power space. AB - It appears now to be recognized that traditional clinical representations of astigmatic power, including sphere, cylinder, and axis, in particular, do not lend themselves directly to satisfactory quantitative analysis. For purposes of analysis, the clinical representations need first to be transformed into representations in dioptric power space. It turns out, however, that characteristics of the clinical measurements carried over into dioptric power space can be a source of spurious conclusions reached in such studies. The source of the problem lies in the nature of sphere, cylinder, and axis and in the discreteness (multiples of 0.25 D, usually, in sphere and cylinder and 1 or 5 degrees in axis) of the clinical measurements. As a consequence, scatter plots of clinical measurements in dioptric power space may show patterns and structures, including clusters, arcs, and moire effects. All the structures are artifacts of the discreteness in sphere, cylinder, and axis; they have no other physical basis. Furthermore, the clinical measurements can show departures from normality that are also purely artifact. By learning to recognize artifact in the scatter plots, the researcher can overcome some of the problems. But because of the assumption of normality underlying many statistical procedures, the problem of distortions in the distributions remains. The distortions may weaken the confidence with which inferences can be made or even lead to erroneous conclusions. The purpose of this paper is to draw attention to the problems of artifact in analyses of clinical data and to suggest ways of overcoming it or avoiding it at least in part. PMID- 11763259 TI - The effect of flicker rate on measured visual field extent in very young children. AB - PURPOSE: To investigate the effect of flicker rate on measured visual field extent in toddlers. METHODS: A total of 270 full-term children (90 each at 11-, 17-, and 30-months of age) and 36 adults were tested binocularly with an LED static perimetry procedure using a black double-arc perimeter. Each subject was tested with one of three flicker rates: 0, 3, or 10 Hz. The median farthest location seen and an interpolated estimate of the location at which 50% of the subjects detected the peripheral stimulus were calculated for each age group for each flicker rate. RESULTS: For 11-, 17-, and 30-month-old subjects, but not adults, flickering stimuli produced a larger measured visual field extent than nonflickering stimuli. For the 10-Hz stimuli, measured visual field extent in children did not differ from that of adults. CONCLUSIONS: In infants and young children, binocular measured visual field extent is enhanced by peripheral stimulus flicker. Maturity of the measured visual field depends on the stimulus parameters used during testing. PMID- 11763260 TI - Polychlorinated biphenyls (PCBs) in sediments of the southern Baltic Sea--trends and fate. AB - Polychlorinated biphenyls (PCBs) have been determined in recent [0-1(2), 1(2)-5 and 5-10 cm deep layers] sediments from different sites of the southern Baltic Sea, including the Szczecin Lagoon, collected from May 1996 to October 1999, i.e. before and after the great flood in Poland of July/August 1997. The PCB distribution has been correlated with location and hydrological conditions as well as with organic carbon, algal pigments and their derivatives in the sediments. The sum of PCB (seven congeners) was equal to approximately 1-149 ng/g dry wt., on average this was rather low (up to 40 ng/g). There was a decreasing trend in PCBs concentrations in the bottom sediments of the southern Baltic in 1996 but considerable amounts were still accumulated there. The flood of 1997 caused a distinct increase of PCB concentration level in the sediments, which again showed a decreasing trend in the next few years. This illustrates that at present the main source of PCBs for the southern Baltic are not a direct consequence of human activity, but from floods and heavy rains washing these compounds from land to the sea. Algae and algal detritus play an important role in the transport and distribution of PCBs in the southern Baltic. High correlation of PCBs with chlorophyll a derivatives--products of zooplankton grazing--indicates that PCBs are ingested by zooplankton with phytoplankton and then exuded with fecal pellets. PCBs bound to algal detritus or to fecal pellets in the water column are transferred to sediments, there they may be trapped either in a bonded and unchanged form or resuspended, remobilized and/or dechlorinated, depending on their properties and environmental conditions. PMID- 11763261 TI - The fate of 137Cs in coniferous forests following the application of wood-ash. AB - In the future, it may become common practice in Swedish forestry to recycle wood ash, a waste product of the combustion of bio-fuel. As a consequence of the Chernobyl radioactive fallout in 1986, large areas of central Sweden were contaminated. Application of recycled wood-ash, originating from contaminated areas, to a previously uncontaminated forest, risks an increase in the concentration of radioactive 137Cs. We measured 137Cs radioactivity in different parts of coniferous forests in seven field experiments. Measurements of radioactivity were made 5-8 years after an application of wood-ash equivalent to 3000 kg ha(-1). The sites, in a north-south transect across Sweden, have a background radioactivity ranging from 0 to 40 kBq m(-2), the higher levels are mainly a result of the Chernobyl fall-out. Depending on its origin, the radioactivity of the applied wood-ash ranged from 0.0 to 4.8 kBq kg(-1), corresponding to 0.0-1.44 kBq m(-2). In autumn 1999, samples were taken from the soil, field vegetation, needles and twigs and the levels of 137Cs determined. In addition, soil samples were analysed for extractable K. The highest 137Cs concentration was found in the soil. At six of the seven sites there were no statistically significant effects of wood-ash application on 137Cs activity. This was despite the fact that the wood-ash had, in one case, added the same amount of radioactivity as the background. However, at one site with intermediate 137Cs deposition (10-20 kBq m(-2)), there was a statistically significant decrease in 137Cs radioactivity in the soil, needles and twigs from the plots treated with wood-ash. The decrease in radioactivity was partly due to the fact that one of the main constituents of wood-ash is K, which is antagonistic to 137Cs. Based on our results, it appears that application of wood-ash containing 137Cs does not necessarily increase the 137Cs radioactivity in plants and soil. However, some of the observed effects could be a result of the low number of replicates used in this study. PMID- 11763262 TI - Selected persistent organochlorine pollutants in Romania. AB - Selected persistent organochlorine pollutants, including PCBs, DDT and its metabolites (DDTs) and hexachlorocyclohexane isomers (HCHs) were determined in soil, animal fat and human serum samples from Romania. All methods were rigorously tested and adequate quality control was ensured. Soil samples from lassy County showed a lower contamination with organochlorines than samples from other Romanian regions. While DDTs concentrations in soil were significantly higher at rural sites, only few samples (three out of 47) exceeded the official Romanian norms for DDTs. PCBs concentrations were low in rural sites (< 8 ng/g soil), but rather high (up to 134 ng/g soil) in urban soils collected mostly from parks (Bucharest, Arad, Baia Mare, Pitesti and Ploicsti). Animal fat samples from lassy showed high concentrations of organochlorine pesticides (HCHs concentrations up to 12370 ng/g fat), but similar PCB concentrations when compared with Arad samples. Two samples (from 24) exceeded the EU norms (1000 ng/g fat) for HCHs and DDTs in animal fat. Organochlorines were found in higher concentrations in some samples of human serum from Timisoara due to a broader age range. Samples of human serum from lassy mothers showed higher HCHs and DDTs concentrations than samples from a similar group from Antwerp, Belgium. HCB and PCBs were higher in Antwerp cohort. Romanian samples showed a higher ratio DDT/sigmaDDTs, but similar ratios PCB 153/sigmaPCBs. PMID- 11763263 TI - Response of antioxidant enzymes in freshwater fish populations (Leuciscus alburnoides complex) to inorganic pollutants exposure. AB - Evidence is accumulating indicating the importance of antioxidant enzyme activity measurements in eco-toxicological studies, as they may constitute markers for exposure to a large variety of pollutants. Variation of antioxidant enzymes, superoxide dismutase (SOD) and glutathione S-transferases (GST) and the effect of heavy metals and selenium exposure on these enzymes were investigated in the livers of Iberian endemic minnows (Leuciscus alburnoides complex) captured in a copper (Cu) mining area. Higher hepatic levels of copper and selenium were always observed in fish captured at the polluted site relative to the reference area population, reflecting the environmental monitoring results. A seasonal fluctuation in zinc and selenium levels for both populations was also observed which could be related to gonad maturation. The activity of SOD did not show significant regional alterations, but a seasonal variation occurred presumably associated with the Leuciscus life cycle. The GST activity was higher in the fish population from the polluted area (except in spring) and GST variability was associated with selenium and copper levels when both regions were compared. The increased GST activity was probably a metabolic adaptation to the continuous exposure to higher levels of those elements. PMID- 11763264 TI - Peripheral blood cells among community residents living near nuclear power plants. AB - Information about hematopoieses as a result of exposure to very low levels of radiation is scarce. To investigate the human hematopoietic effect of very low level radiation exposure, measurements of peripheral blood components were performed among 3602 men and women, aged 35 and above, living in a community near two nuclear power installations in Chinshan, Taiwan. The radiation level that each individual was exposed to was represented by a surrogate level, '1/D2(1i) + 1/D2(2i)', a transformed distance from each individual's residence to the two power plants D1 and D2. In addition to comparing average hematology measurements, multiple regression analyses were done to include age, gender, smoking, drinking status and the surrogate radiation exposure level as independent variables. Univariate and bivariate analyses showed that the hematology measurements had significant associations with age, gender, smoking or drinking. The multiple regression analyses revealed that significant positive associations with '1/D2(1i) + 1/D2(2i)' were found for hemoglobin, hematocrit, platelet, white blood cell and red blood cell. The platelet count might increase for 208.7 x 10(3)/microl if the exposure from the nuclear plants increased by one exposure unit. This type of association implies that those who lived closer to the nuclear power installation had a higher blood cell count; we suspect that this could be a type of radiation hormesis. PMID- 11763265 TI - Historical contamination of Yukon Lake sediments by PCBs and organochlorine pesticides: influence of local sources and watershed characteristics. AB - PCBs and other persistent organochlorine (OC) pesticides were analyzed in sediment cores collected from six lakes in Yukon Territory and one in northern British Columbia, Canada, with the objective of establishing sources and historical trends of these contaminants. DDT was found to be the most prominent OC in the sediment profiles of most of the lakes. Maximum sigmaDDT levels (3.47 2680 ng g(-1) dw) were observed in sediment slices dated to the 1950s from lakes near populated areas. In contrast, in more remote lakes (Hanson, Kusawa and Lindeman), the maximum sigmaDDT concentrations were observed in the sediments dated to the 1970s. Highest sigmaPCB and sigmaDDT concentrations were measured in sediments from Watson Lake, near a suspected PCB waste disposal site and in a region where DDT was heavily applied in the 1950s and 1960s. Elevated sigmaPCB concentrations [16.1-93.6 ng g(-1) dry weight (dw)] were also observed in sediments from lakes situated near populated areas, relative to Kusawa and Lindeman (11.1 and 12.7 ng g(-1) dw, respectively). Recent sigmaPCB fluxes ranged from 621 ng m(-2) y(-1) in Kusawa Lake to 16400 ng m(-2) y(-1) in Little Atlin Lake. The extremely high sedimentation rate (2050 g m(-2) y(-1)) in glacial fed Lindeman Lake gave rise to elevated fluxes of sigmaPCB (2410 ng m(-2) y(-1)) and other OCs, despite much lower concentrations in the sediment. Levels of hexachlorocyclohexanes (sigmaHCH), chlordane-related compounds (sigmaCHL), and chlorobenzenes (sigmaCBz) were in the low ng g(-1) (dw) range in all lake sediments, similar to concentrations previously reported for Arctic lakes in Canada, indicating that their major source was long range atmospheric transport. Contamination of the lakes with PCBs and DDT near populated areas of the Yukon Territory appears to be a result of regional activities rather than long range transport and deposition. The results also point to glacial runoff as a significant source of OCs to small, high elevation lakes (Lindeman), but not to larger lakes within the Yukon River drainage basin that are also affected by glacial sources (Kusawa, Laberge). PMID- 11763266 TI - Riparian zone influence on stream water chemistry at different spatial scales: a GIS-based modelling approach, an example for the Dee, NE Scotland. AB - A geographical information system (GIS-ARC/INFO) was used to collate existing spatial data sets on catchment characteristics to predict stream water quality using simple empirical models. The study, based on the river Dee catchment in NE Scotland, found that geological maps and associated geochemical information provided a suitable framework for predicting chemical parameters associated with acidification sensitivity (including alkalinity and base cation concentrations). In particular, it was found that in relatively undisturbed catchments, the parent material and geochemistry of the riparian zone, when combined with a simple hydrological flow path model, could be used to accurately predict stream water chemistry at a range of flows (Q95 to > Q5) and spatial scales (1-1000 km2). This probably reflects the importance of the riparian zone as an area where hydrological inputs to stream systems occur via flow paths in the soil and groundwater zones. Thus, evolution of drainage water chemistry appears to retain the geochemical characteristics of the riparian area as it enters the channel network. In more intensively managed catchments, riparian land use is a further influential factor, which can be incorporated into models to improve predictions for certain base cations. The utility in providing simple hydrochemical models, based on readily available data sets, to assist environmental managers in planning land use in catchment systems is discussed. PMID- 11763267 TI - Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 1: physiology, function and sampling of placenta for elemental characterisation. AB - Choice of specimen from human subjects for monitoring pollutants proven to be detrimental to human health depends on the criteria chosen, namely real-time monitoring (RTM) or long-term monitoring (LTM). Specimens such as whole blood, urine, saliva and breast milk are commonly used from living subjects for RTM of toxic metals. However, sampling blood requires an invasive procedure. On the other hand, hair (with some limitations), bone (especially for the assessment of bone seeking elements), adipose tissue (mainly for organic pollutants) and liver (for both organic and inorganic toxicants) are used as specimens for LTM. With the exception of hair, generally these specimens are obtained at post-mortem. In context of health-related biomonitoring, placenta as a specimen has not received as much attention as it deserves. It is a unique sample requiring no invasive procedure, and offers possibilities for RTM, in particular as a dual purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. Obtaining representative samples of placenta for elemental composition studies is a difficult task, because of heterogeneous mix of placental cells and decidual matter tainted with maternal and fetal blood. Therefore, the present sampling practices for placental tissue, and guidelines to safeguard the validity of the sampled material have been reviewed in part 1 with the following conclusions: medico-legal and ethical matters should be properly addressed before collecting the placenta; it is advisable to collect the entire placenta even if it includes the umbilical cord; further preparatory work is to be carried out in a clean laboratory and depends upon the purpose of the investigation; homogenising the entire sample may prove to be technically challenging but this step is crucial to obtain representative samples, handling the entire sample may be unavoidable; and an alternative method of procuring representative samples would require random samples from multiple sites, pooled, homogenised and assayed to confirm homogeneity. PMID- 11763268 TI - Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 2: essential minor, trace and other (non-essential) elements in human placenta. AB - A survey of elemental composition of the human placenta was undertaken to evaluate reference values for minor and trace elements (essential and non essential). The new data collection was narrowed down to results generated between the period of 1975-2000, since analytical methodology was becoming increasingly reliable with time for many elements. The search revealed the following results (microg/g, based on wet weight): Ca = 770; Cl = 1900; K = 1685; Mg = 100; Na = 360; P = 1700; and S = 350. However, Na, P and S need further confirmation. For a group of essential trace elements following average values were evaluated (microg/g, based on wet weight): Co = 0.007; Cr = 0.03; Cu = 0.9; Fe = 69; I = 0.005; Mn = 0.08; Mo = 0.02; Se = 0.2; and Zn = 10. However, the iodine value needs further confirmation. In addition, information values have been identified for a number of so-called non-essential elements such as Ag, Au, B, Ba, Br, Cs, F, La, Rb, Sb, Sc, Si, Sn, Sr, Ti, V and W. The survey results for toxic trace elements As, Cd, Hg, Ni and Pb are discussed in part 3 of this paper along with placenta as a biomonitor for toxic trace elements. PMID- 11763269 TI - Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 3: toxic trace elements in placenta and placenta as a biomarker for these elements. AB - The human placenta as a body component is exposed to several harmful substances, depending upon the environmental conditions encountered. In the case of toxic metals, placental tissue can be regarded as a dual biomarker to assess maternal and fetal health. The average range of concentrations for toxic trace elements in placenta based on wet weight are found to be: cadmium 1-6 ng/g; total mercury 2 13 ng/g; methyl mercury 1-14 microg/g; and lead 5-60 ng/g. The placenta appears to be at least a partial barrier for Cadmium. Cadmium transport includes a broad variety of mechanisms. Once in circulation, it mainly interferes with Ca and Zn transportation. On the other hand, placenta appears to be a weaker harrier for Pb than for Cd. In the case of Hg, predominantly the organic form is absorbed and readily crosses the placenta. In fetal blood, the organic mercury content is equal or even greater than in maternal blood, raising questions on normal fetal development. Placenta as a biomarker could be taken as an alternative to repeated maternal blood sampling for assessing lead exposure in utero. Placenta samples are usually obtained at the time of parturition, a one-time event. Hence, each pregnancy has to be looked upon as an RTM (real time monitoring) process since the affected species is exposed to the placental source of pollutants only during the course of that particular pregnancy. PMID- 11763270 TI - Partitioning and speciation of chromium, copper, and arsenic in CCA-contaminated soils: influence of soil composition. AB - This study focused on the influence of soil composition and physicochemical characteristics on the retention and partitioning of Cu, Cr and As in nine chromated copper arsenate (CCA) artificially contaminated soils. A statistical mixture design was used to set up the number of soils and their respective composition. Sequential extraction and modified solvent extraction were used to assess Cu and Cr partitioning and As speciation [As(III) or As(V)]. It was found that peat had a strong influence on CEC (232 meq/100 g), on buffer capacity and on Cu and Cr retention, whereas kaolinite's contribution to the CEC was minor (38 meq/100 g). Average metal retention in mineral soils was low (58% for Cu and 23% for Cr) but increased dramatically in highly organic soils (96% for Cu and 78% for Cr). However, both organic and mineral soils demonstrated a very high sorption of added As (71-81%). Levels of Cu and Cr in a soluble or exchangeable form (F1) in highly organic soils were very low, whereas the levels strongly bound to organic matter were much higher. Conversely, in mineral soils, 47% of Cu and 18% of Cr were found in F1. As a result, Cr and Cu in moderately and highly organic contaminated soils were present in less mobile and less bioavailable forms, whereas in mineral soils, the labile fraction was higher. The modified method used for selective determination of mineral As species in CCA-contaminated soils was found to be quantitative and reliable. Results revealed that arsenic was principally in the pentavalent state. Nevertheless, in organic soils, arsenite was found in significant proportions (average value of 29% in highly organic soils). This indicates that some reduction of arsenate to arsenite occurred since the original species in CCA is As(V). PMID- 11763271 TI - Lead and traditional Moroccan pharmacopoeia. AB - The use of traditional cosmetics and remedies such as kohl and henna is very common in Morocco, especially among women, children and babies. Kohl is a dangerous eye cosmetic. It is usually mixed with other harmful substances, then applied on women's eyebrows and used in skin treatments for infants. Henna is another traditional product, with religious associations, which has been widely used over the centuries for cosmetic and medical purposes. Many people add various herbs or other substances to the henna in order to strengthen it or to give it a stronger colour. Our results were reassuring in that the concentrations of lead found in non-elaborate (henna only) samples of henna were low. However, when henna was mixed with other products (elaborate henna), these concentrations increased. Lead concentrations in kohl were very high however, unlike henna, were lower in mixed kohl as mixing with other products diluted the concentration of lead. Nevertheless, in both types of kohl, lead concentrations were very high and consequently constitute a risk for public health, particularly for children. PMID- 11763272 TI - Organochlorine pesticide, polychlorinated biphenyl and heavy metal concentrations in wolves (Canis lupus L. 1758) from north-west Russia. AB - The wolf Canis lupus is a major terrestrial predator in eastern Europe and, as a top carnivore, may be exposed to high concentrations of contaminants that are readily transferred through the food chain. Despite this, there are few published data on pollutant and pesticide levels in wolves. This study utilised tissues from animals legally killed by hunters for other reasons (animals were not killed for the purposes of this study) to carry out the only detailed investigation of contaminants in wolves in Europe and the first in animals from Eastern Europe. The livers of 58 wolves from the Tver and Smoliensk regions of northwest Russia (54 degrees N 31 degrees E to 57 degrees N 35 degrees E) were analysed for seven organochlorine pesticides, 24 PCB congeners, Aroclor 1254-matched summed PCBs (sigmaPCBs), total mercury, cadmium and lead. Cadmium, most of the organochlorine pesticides and many PCB congeners were not detectable in any of the wolves. Hexachlorobenzene, alpha-HCH, pp'DDE, PCB congeners 118, 138, 149 and 156 and lead were detected in up to 6% of livers. Dieldrin, PCB congeners 153, 170 and 180, sigmaPCBs and mercury were detected more frequently. Contaminant levels were generally low; maximum wet weight concentrations of any of the organochlorine pesticides, sigmaPCBs and mercury were less than 0.1, 1 and 0.25 microg g(-1), respectively. PCB congeners 153, 170 and 180 accounted for 41% of the sigmaPCBs. Dieldrin, sigmaPCBs and mercury concentrations did not vary significantly between males and females nor between adult and juvenile (< 12 months old) wolves apart from the sigmaPCB concentration, which was on average five times higher in adults than juveniles. Liver residues were generally below the level normally associated with adverse effects except for lead levels which exceeded the critical 5 microg g(-1) dry wt. concentration in three of the 58 animals examined. PMID- 11763273 TI - Georeferenced aquatic fate simulation of cleaning agent and detergent ingredients in the river Rur catchment (Germany). AB - The Geography-referenced regional exposure assessment tool for European rivers (GREAT-ER) 1.0 was developed in the context of environmental risk assessment of chemicals to calculate the aquatic fate of 'down-the-drain' chemicals in surface waters due to point release. As a follow-up project, the river Rur catchment in Germany was incorporated into the system. This included aspects of data collection, modelling and monitoring. Investigated substances are the four detergent and cleaning agent ingredients boron, linear alkylbenzene sulfonate (LAS), nitrilotriacetate (NTA) and ethylenediaminetetraacetate (EDTA). Results of the catchment's incorporation into the system and a comparison of GREAT-ER simulations with different monitoring results are both given. It is shown that data sets derived from a literature review can be used to calculate concentration profiles that are in the range of measured values. Since the model establishes a causal relationship between emission sites and data on the one hand, and observed concentrations in the receiving surface waters on the other, the simulation results can be used to explain monitoring data. PMID- 11763274 TI - Tolerance changes of the potworm Enchytraeus albidus after long-term exposure to cadmium. AB - Cadmium tolerance in Enchytraeus albidus was assessed for non-acclimatised organisms, as well as populations acclimatised for 18 months to 32, 100 and 320 mg Cd/kg dry wt. of standard artificial soil. Despite the increased concentration of metallothionein-like proteins in the acclimatised potworms, no changes in sensitivity to acute and chronic (juvenile production) cadmium toxicity could be observed. The 21-day LC50s ranged from 627 for the non-acclimatised enchytraeids to 748 mg Cd/kg dry wt. for the organisms acclimatised for 18 months to a cadmium concentration of 320 mg/kg dry wt. The 42-day EC50s varied from 96.2 (73.6-115) for the organisms acclimatised to 32 mg Cd/kg dry wt. to 234 (186-290) mg Cd/kg dry wt. for those acclimatised to 100 mg Cd/kg dry wt., while the value was intermediate for the non-acclimatised organisms and those acclimatised to the highest cadmium concentration. The elevated content of metallothionein-like proteins apparently only served for the detoxification of the increased cadmium body burdens. PMID- 11763275 TI - Distribution of lanthanoids, Be, Bi, Ga, Te, Tl, Th and U on the territory of Bulgaria using Populus nigra 'Italica' as an indicator. AB - The concentrations of lanthanoids, Be, Bi,Ga, Te, Tl, Th and U have been determined using ICP-MS for 100 standardized samples of poplar leaves collected from the territory of Bulgaria. The investigated elements are log-normally distributed on the territory. Using cluster analysis of the analytical data the samples were grouped according soil type on which the plants are growing. PMID- 11763276 TI - Chemicals and biological products used in south-east Asian shrimp farming, and their potential impact on the environment--a review. AB - A wide variety of chemicals and biological products are used to treat the water and sediment of ponds in semi-intensive and intensive south-east Asian shrimp farming. These products are also often used in shrimp hatcheries and to disinfect equipment for shrimp pond management. In spite of the size and importance of the shrimp farming industry in several south-east Asian countries, documentation of the quality and quantity of chemicals and biological products used during farming is scarce. This paper is a compilation of the literature available on substances used in shrimp farming, and the possible environmental effects of these products are analysed to the extent allowed by the limited information. The role of shrimp farm managers, the chemical industry, governments, inter-governmental organisations and scientists in the development of a sustainable practice is discussed. It is concluded that shrimp farmers should reduce the use of chemicals and biological products because of the risks to the environment, human health and to production, and also, because many chemicals and biological products used in pond management have not been scientifically shown to have a positive effect on production. Clearly, the use of some chemicals, i.e. certain antibiotics, poses a risk of danger towards human health. Some chemicals used in shrimp farming, such as organotin compounds, copper compounds, and other compounds with a high affinity to sediments leave persistent, toxic residues, and are likely to have a negative impact on the environment. However, to assess the reality of these risks, substantial new information about the quantity of chemicals used in marine south-east Asian shrimp farming is needed. PMID- 11763277 TI - Disability, injury and ergonomics intervention. AB - PURPOSE: Disability due to work injury, trauma or disease is prevalent in our society. Also, due to slower growth of population and rapid increase in ageing population there may be an increasing pressure on shrinking labour pool. The purpose of this study is to review disability profile with common disabilities, socioeconomic impact of these disabilities, make a case for ergonomics as an enabler, and provide a couple of case studies to illustrate the point. METHOD: Major disability statistical records were reviewed to reveal rates of disability in some countries of the world. Among them the age and gender association of disability has been described. Furthermore the major categories of disabilities associated with systemic disorders and their gradations have been described, e.g. cardiovascular conditions, pulmonary conditions and joint diseases. Finally, using a feed forward mechanism a specific and customized ergonomic intervention was designed for two workers with knee injury. RESULTS: The prevalence of disability has been reported to range between 0.2% -20.9%. A significant association of disability with ageing was reconfirmed. A significant socio economic impact of disability including differential employment rate for normal and disabled was discovered. A strategy and a means to achieve increased functionality in people with disability using ergonomic intervention has been described. Using a custom designed shin pad for rehabilitation of two workers with injured knee who were also on compensation were successfully returned to work many weeks before they may have been able to resume their work. CONCLUSION: Using a functional classification and developing functional profiles of people with disability may allow ergonomists to develop generic as well as specific solutions to successfully intervene in many cases and improve their functional capacity. PMID- 11763278 TI - Early prognosis for low back disability: intervention strategies for health care providers. AB - PURPOSE: Disability following acute occupational low back pain (OLBP) represents a significant and preventable health outcome, yet confusion about prognostic factors have limited the development of effective, targeted interventions for those at greatest risk. The purpose of this study was to synthesize findings from available studies of prognostic factors for OLBP disability in a clinically relevant framework. METHOD: A systematic search of the MEDLINE database was conducted to identify empirical studies assessing the value of various prognostic factors to predict extended disability after an acute episode of OLBP. Relevant studies were screened based on a number of inclusionary criteria. Prognostic factors were catalogued, summarized, and evaluated based on agreement across studies, and clinical recommendations were developed based on the evidence. RESULTS: Of 361 studies of OLBP disability found, 22 met specific criteria for inclusion. Significant prognostic factors included low workplace support, personal stress, shorter job tenure, prior episodes, heavier occupations with no modified duty, delayed reporting, severity of pain and functional impact, radicular findings and extreme symptom report. Physicians can decrease OLBP disability by using standardized questionnaires, improving communication with patients and employers, specifying return to work accommodations, and employing behavioural approaches to pain and disability management. Future studies should evaluate interventions guided by prognosis. PMID- 11763279 TI - Serial plaster casting to correct equino-varus deformity of the ankle following acquired brain injury in adults. AB - PURPOSE: Proposed mechanisms via which serial casting might effect increased joint range, muscle extensibility and reduced reflex excitability are outlined in this review. Support for these mechanisms stems largely from animal experimental studies. The applicability of these data to human muscle is unknown. ISSUES: Equino-varus deformity of the ankle is a common secondary complication of acquired brain injury. It results from a combination of sequelae of the brain injury and subsequent immobility, including hypertonia, reduced muscle length and increased stiffness. Some evidence exists for the efficacy of serial plaster casts in the treatment of equino-varus deformity, although most reported studies are uncontrolled and involve small numbers of subjects. Serial casting has been shown to result in decreased resistance to passive lengthening and a reduction in dynamic reflex excitability within the lengthened muscles in children with cerebral palsy. Currently documented effects of serial casting in brain injured adults are limited to changes in range of maximal passive dorsiflexion. CONCLUSION: Serial casting should be considered as an adjunct to therapy aimed at improving functional mobility. A variety of therapeutic interventions have been used to augment the effect of the casting regime. Factors that have been demonstrated to be associated with a favourable outcome from serial casting, and recommendations for future research are also discussed in this review. PMID- 11763280 TI - Cross cultural differences in health related quality of life in adolescents with cystic fibrosis. AB - PURPOSE: Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL-measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. METHOD: The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV1% predicted and BMI) were also recorded. RESULTS: The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. CONCLUSIONS: The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36. rather than a consequence of their disease or its management. PMID- 11763281 TI - Verbal autopsy: a necessary solution for the paucity of mortality data in the less-developed countries. AB - Although global disease burden can best be described using accurate and reliable mortality data, many investigators rely solely on death certificates, despite the fact that many of the less-developed countries (LDCs) do not have mandated death certifications. In many of these LDCs, particularly in remote areas, verbal autopsy (VA) may be a surrogate for death certificates in ascertaining causes of death. The main benefit of using VA stems from the fact that it is based on laypersons' observations of the diseased, and therefore does not require medical training. Because of human and economic resource constraints in many LDCs, investments in infrastructures for collecting mortality data needed for the planning, monitoring, and evaluation of health are unlikely in the immediate future. Investment in rural health workers who are trained in VA may prove useful in increasing the quality and availability of mortality data from many LDCs. Rural health workers are essentially 'foot doctors' in many of these countries, whose familiarity with nooks and crannies of villages would be beneficial in the collection of needed mortality data. There is a need for international development agencies, such as the World Health Organization, to devote resources for training rural health workers in order to increase the availability of mortality data for describing worldwide disease burdens. PMID- 11763282 TI - HFE mutations in African-American women with non-insulin-dependent diabetes mellitus. AB - The aim of this study was to compare the frequencies of HFE mutations in African American women with non-insulin-dependent diabetes mellitus (NIDDM) to that of controls and to determine whether these mutations are associated with NIDDM and iron overload. We studied 167 African-American women with NIDDM. The 71 non diabetic controls were African-American female controls. HLA-A and -B typing and HFE mutation analysis for C282Y and H63D alleles were performed using standard molecular genetic techniques. The frequencies of C282Y and H63D were not significantly different in NIDDM patients and controls. C282Y was observed in 0.59% of patients and 1.41% of controls. H63D was observed in 2.99% of patients and 3.08% of controls. All of the NIDDM patients who possessed either C282Y or H63D mutations had normal values of serum ferritin, serum iron and transferrin saturation. A woman who inherited C282Y also possessed HLA-A3, -B7 which is considered part of the ancestral haplotype containing the gene predisposing to hemochromatosis in Caucasians. The frequencies of C282Y and H63D vary in African Americans from different geographic regions of the United States; this variance can be explained by Caucasian admixture. Although most iron overload cases in African Americans bear more resemblance to cases of African iron overload than to those of Caucasian hemochromatosis, rare cases resembling Caucasian hemochromatosis have been observed in African Americans. PMID- 11763283 TI - Determinants of fasting glucose in young Guatemalan adults. AB - OBJECTIVE: To examine correlates of fasting glucose, a precursor for type 2 diabetes mellitus, in young adults in Guatemala, a country undergoing an epidemiologic transition. DESIGN: Cross-sectional. METHODS: Anthropometric, lifestyle, dietary, serum lipid, and socioeconomic characteristic data were collected on 189 men and 201 women (mean age 24.4 years) born in four villages in Eastern Guatemala. We used linear regression to identify parsimonious predictive models, including 2-way interactions. RESULTS: In men, mean fasting glucose was 87.3 mg/dL (SD 10.2); our model explained 30% of variance. Body mass index (BMI), abdomen-to-hip ratio (AHR), and total cholesterol showed graded positive effects. BMI and AHR interacted (P<.001); men with high BMI and high AHR had the highest fasting glucose levels. No dietary factors independently predicted fasting glucose. In women, mean fasting glucose was 83.9 mg/dL (SD 8.5); 22% of variance was explained by BMI, energy-adjusted fat intake, physical activity, birth village, and current residence (rural/urban). BMI and fasting glucose were positively related. Urban residence interacted with birth village (P=.06) and physical activity (P=.13). CONCLUSIONS: The major conclusion drawn from this study is that increased adiposity, even among lean individuals, is the largest environmental predictor of fasting glucose. Prevention and control of obesity in young adults in transitioning countries are key strategies for the prevention of diabetes. PMID- 11763284 TI - Factors associated with missing birthplace information in a population-based cancer registry. AB - Differences in cancer occurrence within a racial/ethnic group may be influenced by migrant status or level of acculturation, which can indicate variations in environmental exposures. When immigration and acculturation data on individual patients are not available, birthplace may serve as a proxy. As part of a larger study intended to assess the utility of the birthplace variable in the Greater Bay Area Cancer Registry (GBACR), part of the Surveillance, Epidemiology, and End Results (SEER) program, we measured its completeness, and determined whether missing birthplace is associated with patient and hospital reporting source characteristics. Subjects were persons diagnosed with cancer within the GBACR surveillance area during the period 1988-1996. Of the 204,553 subjects, 67% had birthplace recorded in the registry. Deceased persons were 10 times more likely than living persons to have data on birthplace. Racial/ethnic groups which included more foreign-born persons, such as Southeast Asians, tended to have more complete birthplace information than did groups with fewer foreign-born, such as Japanese and Hispanics. The effects of patient and reporting source characteristics on birthplace completeness differed across racial/ethnic groups. These data indicate that completeness of the birthplace variable in the GBACR is biased, and that investigators considering birthplace in analyses of SEER data should consider these biases. For birthplace data to be useful, completeness needs to be improved at the level of the diagnosing facility. PMID- 11763285 TI - Differing postneonatal mortality rates of Mexican-American infants with United States-born and Mexico-born mothers in Chicago. AB - OBJECTIVES: This study sought to determine the relationship between maternal nativity and the postneonatal mortality rate of urban Mexican-American infants. DESIGN: This is a population-based study. METHODS: Stratified and logistic regression analyses were performed on a data set of 1992-1995 computerized birth death records of all Mexican-American infants born to Chicago residents with appended 1990 United States Census income and 1995 Chicago Department of Public Health data. RESULTS: In Chicago, Mexican-American infants (N = 10,599) of US born mothers had a postneonatal mortality rate of 3.2/1,000 compared to 2.1/1,000 for infants (40,813) of Mexico-born mothers; relative risk (95% confidence interval) equaled 1.5 (1.0-2.3). The adjusted odds ratio of postneonatal mortality was 1.4 (1.1-1.9) for Mexican-American infants of US-born mothers. The mortality rate due to preventable causes (sudden infant death syndrome, homicides, non-intentional injuries, and infections) for Mexican-American infants of US-born mothers was twice that of infants of Mexico-born mothers; relative risk (95% confidence interval) equaled 2.2 (1.3-3.8); this nativity differential persisted in non-impoverished communities. CONCLUSION: The postneonatal mortality rate of urban Mexican-American infants with US-born mothers exceeds that of infants with Mexico-born mothers. This nativity disparity is attributable to preventable causes. PMID- 11763286 TI - Use of illegal drugs among mothers across racial/ethnic groups in the United States: a multi-level analysis of individual and community level influences. AB - OBJECTIVE: To obtain adjusted one-year prevalence estimates and compare multi level correlates of marijuana, cocaine, crack, or heroin use among 4,678 mothers of minor children in the United States across racial/ethnic populations. METHODS: The study used publicly available data from the 1997 National Household Survey on Drug Abuse. Hierarchical generalized linear modeling (HGLM) procedures were used to test drug use variation among non-Hispanic White, non-Hispanic Black, and Hispanic mothers across US neighborhoods. RESULTS: Black mothers were 40% less likely to use illegal drugs than were White mothers, and Hispanic mothers were 72% less likely than were White mothers to use drugs, after adjusting for demographic and community covariates. Drug use was found to vary across neighborhoods for all racial/ethnic groups. This study identified a positive association between the likelihood of mothers using illegal drugs and their living in neighborhoods with a higher occurrence of drug use. CONCLUSION: To compare drug use across racial/ethnic groups, it is necessary to account for the confounding effects of covariates. Additional research is needed to determine whether non-drug using mothers chose to live in neighborhoods with a lower concentration of drug use, whether residence in these neighborhoods decreases the likelihood of mothers using drugs, or if a reciprocal relationship exists. The mechanisms that link individual drug use and neighborhood characteristics merit further investigation. PMID- 11763287 TI - Multiple-race mothers on the California birth certificate, 2000. AB - OBJECTIVES: Several data systems are beginning to allow respondents to report more than one race. Implications of multiple race reporting for the tabulation of race-specific birth characteristics are largely unknown. This analysis reports selected demographic characteristics and birth outcomes for multiple-race mothers, using California birth certificate data for 2000. DESIGN: Descriptive study of birth records. METHODS: Data were drawn from 530,305 electronically registered births. Demographics and birth outcomes were analyzed by race of mother for six multiple-race/ethnic groups with >300 births. RESULTS: 1.7% of mothers reported more than one race on the birth certificate. The most common multiple-race group reported was non-Hispanic Asian/White, followed by Hispanic/American Indian or Alaska Native/White. Characteristics varied widely among multiple-race subgroups, as well as between multiple-race groups and their single-race counterparts. For example, among multiple-race mothers, the proportion of births to teenage mothers was lowest among non-Hispanic Asian/White mothers (9%); this was significantly higher than percentages for non-Hispanic Asian or non-Hispanic White mothers (4% and 6%, respectively). CONCLUSIONS: Understanding the influence of multiple-race reporting on trends and comparisons in birth outcomes will be a challenge for public health researchers. PMID- 11763288 TI - HIV-infected American Indians/Alaska natives in the Western United States. AB - OBJECTIVE: We sought to describe HIV-infected American Indians/Alaska Natives (AI/ AN) in the western United States. DESIGN: One hundred fifty-one Al/AN and 11,344 non-AI/AN HIV-infected patients in Seattle, Denver, and Los Angeles were followed by medical record review from January 1989 through June 1998 for the Adult/Adolescent Spectrum of HIV-related Diseases study. METHODS: Bivariate and multivariate statistical analyses comparing HIV-infected Al/AN and non-AI/AN were performed. RESULTS: There were 103 (68%) male and 48 (32%) female Al/AN patients, while non-Al/AN patients were 86% male and 14% female (P<.001). The median age among AI/ AN was 32 years vs. 34 years among non-AI/AN (P = .05). Male Al/AN were more likely than male non-AI/AN to report the dual risks of having sex with men and injection drug use (32% vs. 14%; P<.001) compared with other HIV risks. Median CD4 cell counts were higher in Al/AN than in non-AI/AN (P< or =.001). AI/AN were more likely to be diagnosed with an acute sexually transmitted disease (STD) than were non-AI/AN (11% vs. 4%, P<.001). Five (6%) of AI/AN with AIDS had active pulmonary tuberculosis (TB) compared with 132 (2%) of non-AI/AN with AIDS (P = .02). While 52% of Al/AN and 44% of non-AI/AN had a psychiatric illness (P = .04), and 13% of AI/AN, and 6% of non-AI/ AN had suicidal ideation (P<.001), these associations became non-significant in analyses stratified by alcohol and drug use (P>.05). In adjusted models, survival and progression to opportunistic infection or CD4 cell count less than 200/mm3 did not significantly differ between Al/AN and non-AI/AN. CONCLUSIONS: HIV-infected AI/AN were younger than non-AI/AN, and a greater proportion of Al/AN were women relative to non-AI/AN. AI/AN were more likely to be diagnosed with STDs and TB. In adjusted models, their risks of death and developing AIDS did not significantly differ from those of non-AI/AN. PMID- 11763289 TI - Older Mexican-American women and cancer screening: progress toward targets for healthy people 2000. AB - BACKGROUND: Published information about cancer screening in older Mexican American women is scarce. This study reported the patterns of mammogram and Pap test use among older Mexican-American women. The patterns and associated factors were examined and compared with Healthy People 2000 targets. METHODS: Data were obtained from the Hispanic Established Population for the Epidemiological Study of the Elderly, the largest representative survey of community-dwelling Mexican Americans aged 67 years or over, from the southwestern United States. RESULTS: Among older Mexican-American women, 68.3% reported ever having a mammogram, and 41.2% reported having a mammogram in the last two years; 64.0% reported ever having a Pap test, with 43.6% reported having a Pap test in the last three years. CONCLUSIONS: The data for older Mexican-American women demonstrated that they approached the targets for breast cancer screening, but not for Pap test use. PMID- 11763290 TI - Should body size preference be a target of health promotion efforts to address the epidemic of obesity in Afro-Caribbean women? AB - OBJECTIVE: To determine if 1) Afro-Caribbean women prefer large body sizes, 2) the body size preference of Afro-Caribbean men and women are associated, 3) women's preferences are associated with increased risk of obesity or with weight management behaviors. DESIGN: Population samples of 314 and 487 women, ages 20-55 years, were recruited on Barbados and Dominica with response rates of 74% and 77%, respectively. Body size preferences, stress related variables, and demographic data were ascertained by questionnaire. Height and weight were also measured. On Barbados, body preference data were collected from male partners of participants, and data on intentions to perform weight management behaviors were collected from 175 women. RESULTS: Most women preferred body sizes within normal limits, although women on Dominica had a slightly larger ideal body size (IBS) than did Barbadian women (P<.05). On both islands, the size that women thought men preferred was related to their IBS (P<.0001). Likewise, IBS was associated with increased odds of being overweight (P<.001), however most overweight women (>75%) wanted to be smaller. IBS was not related to the intention to exercise or to eat high fat foods. CONCLUSIONS: It is unlikely that body size preference poses a barrier to intervention efforts to reduce the prevalence of overweight in Afro-Caribbean women. PMID- 11763291 TI - Effects of acculturation and psychosocial factors in Latino adolescents' TB related behaviors. AB - OBJECTIVE: To determine the effect of acculturation and psychosocial factors (self-esteem, social support, mastery, and self-efficacy of medication taking) on Latino adolescents' adherence (completion of treatment, percent of appointments kept, number of treatment weeks, and number of days missed medication in past week) to tuberculosis (TB) treatment. METHODS: Participants (N = 618) were recruited from two clinics located in Los Angeles, California, after receiving a positive diagnosis for Class II TB. RESULTS: Adolescents with high linguistic acculturation and ethnic identification had high mastery, self-esteem and self efficacy. Teens with high ethnic identification perceived more support from parents. Almost 81% of participants completed treatment and the percentage of appointments kept was 76.3%. A high proportion of those completing the treatment regimen had their parents helping them to remember to take the medication. Older teens were less acculturated, less likely to complete treatment, and had a lower rate of appointment keeping. Age and difficulty in getting to the clinics were predictors of adherence. CONCLUSIONS: This study highlights the importance of parental support and sociocultural factors in adherence to TB treatment in this population. PMID- 11763292 TI - Obesity and approaches to weight in an urban African-American community. AB - OBJECTIVES: To describe the prevalence of obesity, associated factors, and current approaches to weight in an inner city African-American community. DESIGN: In-home survey by community health interviewers. SETTING: Baltimore, Maryland. PARTICIPANTS: 2196 community residents identified in a probability sample of census blocks. MAIN OUTCOME MEASURES: Self-reported height and weight and calculated Body Mass Index (BMI), category of BMI, and stated weight goals. RESULTS: Sixty percent of participants were overweight (BMI> or =25 kg/m2), and 31% were obese (BMI> or =30 kg/m2). In multivariate analysis, women, those earning $15,000-30,000, and those aged 45-60 were more likely to be obese; less likely to be obese were smokers, daily drinkers, and those with "good" or "excellent" health. Sixty-one percent of obese participants reported trying to lose weight, while 36% of normal weight participants were trying to gain weight. Of those trying to lose weight, 35% were using recommended approaches, and 26% received "the professional help they needed to control their weight." CONCLUSIONS: Although obesity was prevalent, few were using recommended weight loss strategies and a significant minority of normal weight participants were trying to gain weight, indicating a need for improved weight management and obesity prevention in the African-American community. PMID- 11763293 TI - Neighborhood context and cardiovascular disease risk factors: the contribution of material deprivation. AB - This paper investigates whether neighborhood material deprivation is associated with cardiovascular disease (CVD) risk factors (physical inactivity, diabetes, smoking, body mass index, blood pressure, cholesterol) independent of individual socioeconomic status (SES) in Black, Mexican-American, and White women and men aged 25-64 using data from the Third National Health and Nutrition Examination Survey (1988-1994, N = 9,961). The data were linked to 1990 Census tract characteristics (unemployment, car ownership, rented housing, crowded housing), which were used to construct a neighborhood-level material deprivation index. Results are stratified by gender and race/ethnicity. Multiple logistic and linear regression models were specified using SUDAAN to account for the clustered design. In general, residence in a deprived neighborhood increased the probability of having an adverse CVD risk profile, independent of an individual's SES. For example, after adjusting for SES, Black women living in deprived neighborhoods were at increased risk of being diabetic, being a smoker, and having a higher body mass index and blood pressure compared to Black women living in less deprived neighborhoods (P values <.05). Stronger associations were found between neighborhood deprivation and CVD risk factors in Blacks than in Mexican Americans despite living in similarly deprived neighborhoods. Neighborhood deprivation may influence CVD risk factors through a variety of mechanisms including the availability of healthy environments, municipal services, and political/cultural characteristics. Policies and interventions that address the socioeconomic context in which people live might reduce inequalities in CVD risk factors. PMID- 11763294 TI - The feasibility of using rural health workers to determine cause of death in remote regions of Cameroon, West Africa. AB - The validity of the recent Global Burden of Disease Study (GBDS) was compromised by the lack of adult mortality data in developing countries, particularly in Sub Saharan Africa. Verbal autopsies, in which health workers (HW), using questionnaires and algorithms, interview surviving family members to determine the cause of death, have proven useful in establishing priorities for the allocation of limited health care resources. Most reports, however, have come from large population centers. The feasibility of using health workers trained in verbal autopsy methodology to operate in remote rural areas of Africa has had limited testing. The records of 40 villagers who died in a Mission Hospital of the Northwest Province of Cameroon were reviewed, and the hospital discharge diagnosis, made by the attending physician, compared with that obtained by HW who administered a verbal autopsy to the family. In 70% of the cases the physician and HW were in exact agreement. Such a method, if confirmed in other studies among rural populations, may be an important approach to determining cause of death in many developing countries. PMID- 11763295 TI - The association between community context and mortality among Mexican-American infants. AB - Mexican-American infants have surprisingly low mortality rates, given their high risk demographic characteristics. One explanation for this well-known paradox is the beneficial influence of a traditional Mexican cultural orientation. However, many studies have focused on individual, rather than contextual, markers of acculturation to explain the reasons for this paradox. This study incorporated community-level data into the analysis to further elucidate the Mexican paradox. Data from the National Linked Birth and Infant Death files for 1995-1997 were used to stratify infants born in counties of Arizona, California, New Mexico, and Texas into tertiles based on the proportion of Mexican births in each county. We calculated mortality rates for infants in each tertile. Logistic regression, with generalized estimating equations, was used to calculate odds ratios comparing infant mortality in low and medium concentration counties to high concentration counties. Odds ratios were adjusted for maternal age, education, parity, marital status, and maternal nativity status. Among Mexican-American infants, mortality rates ranged from 4.3 in counties with high proportions of Mexican births to 5.5 in counties with low proportions of Mexican births. However, this association was limited to US-born mothers, whose rates ranged from 4.4 in high concentration counties to 7.0 in low concentration counties (adjusted OR, 1.56 [1.35-1.81]); a substantial proportion of that difference was due to lower birth-weight specific mortality among normal birth-weight infants (1.9 vs. 3.1 deaths/1,000 live births). Among infants with Mexico-born mothers, there was no association between community context and mortality (OR, 1.01). Residence in counties with high proportions of Mexican births had a positive influence on birth outcomes among women of Mexican origin born in the United States. Exposure to the Mexican culture may reinforce healthy behaviors that Mexican-American women may lose through acculturation. PMID- 11763296 TI - Hysterectomy: beliefs and attitudes expressed by African-American women. AB - OBJECTIVE: Racial/ethnic differences in the rates of hysterectomy have been noted historically. The aim of this study was to explore the beliefs and attitudes of African-American women regarding hysterectomy recommended for non-life threatening conditions. METHODS: Women, aged 30-65 years, were recruited from public health clinics and community agencies for participation in focus groups guided by a semi-structured questionnaire. Transcripts were analyzed both manually and using NUD*IST software. RESULTS: Thirty-eight women participated in six focus groups. Hysterectomy had been recommended for 15% of the women. Four categories and 11 themes emerged from the sessions. Categories included: definitions of hysterectomy and medical indications; resources consulted in the decision-making process; outcomes of hysterectomy; and interactions with the health care community. CONCLUSION: It is important to assess a patient's perceptions and preferences regarding treatment options. The women in this study advocated the delay or avoidance of surgery, or the use of alternative methods of treatment in lieu of hysterectomy for non-cancerous conditions. Physicians who recommend hysterectomy should consider the attitudes, beliefs, and knowledge of patients. PMID- 11763297 TI - A review of endothelin and hypertension in African-American individuals. AB - Endothelin-1 (ET-1) is a peptide with potent vasopressor and mitogenic actions. Moreover, ET-1 displays modulatory effects on the endocrine system, including stimulation of angiotensin II and aldosterone production, and influences ion and fluid transport in the gut and kidney. A number of groups reported that ET-1 is overexpressed in the vasculature in several salt-sensitive models of experimental hypertension. African Americans present with a salt-sensitive and low-renin model of hypertension, and circulating plasma ET-1 levels are significantly increased in this population. The prevalence of hypertension and its complications is also higher in Blacks than in Whites and, despite extensive research, the reasons for this difference are not well understood. We propose that vasoactive, mitogenic, and renal effects of the ET system might contribute to the development, maintenance and/or complications of hypertension in African Americans. PMID- 11763298 TI - G6PD deficiency: its role in the high prevalence of hypertension and diabetes mellitus. AB - Hypertension and diabetes mellitus represent increasing threats to the health of many populations. For reasons not completely understood, the prevalence of these diseases is higher in some ethnic groups than in others. The key to this puzzle may rest with the interplay of a defect of an enzyme-mediated process and the environment. Oxidative stress and impairment of synthesis or release of nitric oxide (NO) are being regarded as causative factors in the pathogenesis of hypertension, diabetes mellitus and atherosclerosis, among other conditions. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been overlooked as a cause of both oxidative stress and a decrease in the generation of nitric oxide (NO). G6PD generates nicotinamide adenine dinucleotide phosphate (NADPH), a co factor in the synthesis of nitric oxide. There is impairment of the production of nitric oxide superoxide and hydrogen peroxide in G6PD-deficient granulocytes. In the polyol pathway, G6PD deficiency causes hyperglycemia, making more glucose available for the non-enzymatic production of advanced glycosylation end products (AGE's), which also causes an increase in superoxide anions and a quenching of nitric oxide. Currently, there are 200 million people worldwide with red cell x linked chromosome defects who, with the persistent ingestion of refined carbohydrates, are at greater risk of developing hypertension or diabetes mellitus than those racial groups without the defect. PMID- 11763299 TI - Ethnic disparities in stroke: the scope of the problem. AB - An excess stroke mortality rate among African Americans is well known and should be considered a national crisis. This excess persists today despite dramatic declines in stroke mortality between 1970 and 1990 for both White and African American men and women. Only a portion of this excess stroke mortality among African Americans can be explained by the higher prevalence of hypertension and diabetes in African Americans, and by the lower average socioeconomic status (SES) among African Americans. The majority of the excess burden of stroke mortality is borne by relatively young (ages 35-64) African Americans and by African Americans living in the Southeastern United States. While overall stroke mortality rates have been rapidly declining for both African Americans and Whites, the magnitude of the relative increased risk of dying from a stroke among African Americans, as compared to Whites, has remained largely unchanged. As such, efforts to reduce ethnic disparities in stroke mortality have been unsuccessful. PMID- 11763300 TI - The perilous effects of racism on blacks. AB - This paper focuses on understanding the perilous effects of interpersonal and institutional racism on the psychological and physiological well-being of Blacks. Interpersonal racism refers to prejudice and discriminatory behaviors directed toward individuals because of their race or ethnicity, and institutional racism refers to formal and informal policies and practices that deny equitable treatment to individuals because of their race or ethnic group affiliation. Racism can psychologically affect Blacks by allowing society to deny their value as individuals, and by compelling them to internalize the racist conceptions of them held by their oppressors. Racist stressors may also lead to increased physiological reactivity which, when sustained for a period of time, can lead to cardiovascular disorders and diseases. To eliminate the effects of racism, it is imperative that further research seek better ways to shield Blacks from these menacing stressors. PMID- 11763301 TI - Managing worry, stress and high blood pressure: African-American women holding it together through 'family'. AB - Strategies to manage worry, stress and high blood pressure (HBP) are little understood from the perspective of African Americans. Using data from a qualitative research study in south Louisiana, this article outlines how participants with HBP managed worry and stress through the formation of family. In an exploration of 314 conversations about 'family,' African-American women were cited by both women and men as mediators of worry, stress, and HBP. Participants did not necessarily define 'family' by blood or marriage relations, unlike the way in which 'family' is presented in most HBP research. 'Family' was often discussed in terms of how relationships with others were utilized to share knowledge about HBP, to address situations that produced HBP elevation, and to marshal resources to manage HBP. PMID- 11763302 TI - Hostility, cultural orientation, and casual blood pressure readings in African Americans. AB - Evidence suggests that hostility correlates with blood pressure levels in African American samples. However, some studies have reported an inverse relationship, while others have found the relationship between blood pressure and hostility to be positive. Other literature suggests health outcomes in general, and blood pressure in particular, are related to cultural orientation in African-American samples. In the present study, six casual measures of blood pressure and heart rate in a sample of 90 African-American college students were aggregated and correlated with measures of hostility and cultural orientation. Correlational and regression analyses revealed a weak positive relationship between hostility and systolic blood pressure. The relationships between the cardiovascular measures and cultural orientation were more consistent. The tendency to embrace mainstream Euro-American values, such as materialism, individuality, and competitiveness, was associated with more rapid heart rate and higher diastolic blood pressure levels for both men and women. The relationship between systolic blood pressure and cultural orientation emerged for men only. The findings encourage further research into the relationship between personality variables and cardiovascular activity in African-American samples. PMID- 11763303 TI - Is there a role for stress management in reducing hypertension in African Americans? AB - When stress is considered as any demand placed on the body, the focus is shifted away from the stressor to how the body responds to the stress. There are psychological, physiological, and behavioral responses to excessive stress. Left unaddressed, cardiovascular or cerebrovascular diseases may occur. The goal of meditation is to decrease mental activity while simultaneously resting and rejuvenating the body. There are internal and external approaches to meditation. The most researched internal form of meditation is the Transcendental Meditation technique, which has been found to reduce stress, depression, anxiety, and blood pressure in hypertensive African Americans. Clinical use of stress management approaches, particularly Transcendental Meditation to reduce hypertension, is supported by randomized clinical trials. Studies with larger numbers of participants and more diverse ethnic groups should continue. PMID- 11763304 TI - The association between racism and high blood pressure among African Americans. AB - National attention is currently being directed toward assessing the association between racism as a stressor and high blood pressure (HBP) among African Americans. Within this context, however, very little research is designed to elucidate the viewpoints of African Americans with HBP on this topic area. The purpose of this article is to explore, critique, and elaborate upon the study of racism as it relates to HBP research. The first portion of this paper reviews the existing literature in this field. Limitations of the current research are outlined. Insights gained as 30 African Americans with HBP talked about racism as a stressor and how it affected their health are subsequently highlighted. Lastly, suggestions for future studies on racism and HBP are postulated. PMID- 11763305 TI - Racism, discrimination and hypertension: evidence and needed research. AB - This paper reviews the available scientific evidence that relates racism to the elevated rates of hypertension for African Americans. Societal racism can indirectly affect the risk of hypertension by limiting socioeconomic opportunities and mobility for African Americans. Racism can also affect hypertension by 1) restricting access to desirable goods and services in society, including medical care; and 2) creating a stigma of inferiority and experiences of discrimination. This paper evaluates the available evidence for perceptions of discrimination. African Americans frequently experience discrimination and these experiences are perceived as stressful. Several lines of evidence suggest that stressors are positively related to hypertension risk. Exposure to racial stressors under laboratory conditions reliably predicts cardiovascular reactivity and such responses have been associated with longer-term cardiovascular risk. Few population-based studies have examined the association between exposure to racial discrimination and hypertension, and the findings, though suggestive of a positive association between racial bias and blood pressure, are neither consistent nor clear. However, the existing literature identifies important new directions for the comprehensive measurement of discrimination and the design of rigorous empirical studies that can evaluate theoretically derived ideas about the association between discrimination and hypertension. PMID- 11763306 TI - Efficacy of a church-based intervention on cardiovascular risk reduction. AB - Lighten Up, a church-based lifestyle program, was developed in collaboration with the Christian community to decrease cardiovascular risk through lifestyle modification. One goal has been to reach the medically under-served in North Carolina and South Carolina. Lighten Up includes a baseline health check (week 1), eight educational sessions (weeks 2-9) combining study of scripture and health messages, a short-term health check (week 10), and a long-term health check (1 year). Baseline and 10-week data obtained for 381 participants (66% Black, 83% women, and a mean of 55 years of age) at 24 sites form the basis of this report. One-year data were obtained in a subgroup of 163 participants (64% Black, 82% women, and a mean of 57 years of age). At baseline, participants had the following significant modifiable risk factors for heart disease: obesity (73%); high blood pressure (55%); high cholesterol (48%); and diabetes (19%). Participants exhibited significant short-term reductions in weight and systolic blood pressure, which were sustained throughout the year. Half or more sessions were attended by 70% of participants. Participants who attended more of the sessions had the greatest reductions in risk factors. Whites appear to have greater reductions in risk factors than did Blacks. However, Lighten Up is reaching both Blacks and Whites with multiple cardiovascular risk factors, and short- and long-term improvements are being made. PMID- 11763307 TI - Conducting health interventions in black churches: a model for building effective partnerships. AB - This article offers a brief review of recent health promotion and disease prevention programs conducted in Black churches and identifies benefits and limitations of conducting interventions in these settings. In addition, a review of three current studies being conducted by our group at the Emory University Rollins School of Public Health provides a discussion of a successful model for forming and maintaining effective partnerships between Black churches and public health organizations. PMID- 11763308 TI - Lipid lowering in high-risk populations: how low should we go? PMID- 11763309 TI - Ethnic disparities in cardiovascular health. AB - Disparities in the cardiovascular outcomes of African-American patients is evident from national, regional, and local statistical data, as well as from the daily practice of medicine. This discussion highlights the complexity of ethnic disparities using a case-based approach with two typical cases from a cardiology practice. These cases underscore the complex interplay of the following factors in ethnic disparities. 1. Excess burden of cardiovascular risk factors in African Americans, with particular emphasis on high blood pressure, diabetes, obesity, physical inactivity, and psychosocial stress. 2. Inadequate knowledge of how personal risk factors are directly linked to atherosclerosis and heart disease. 3. Cultural factors in symptom recognition and health-care seeking behavior. 4. Economic factors influencing access to health care including prevention, diagnosis, and treatment. 5. A combination of psychosocial stress, racism, and frustration leading to sub-optimal interactions with the health care system. 6. Genetics of disease and predisposition to vascular disease and atherosclerosis. We must come to terms with these fundamental factors in the causation and, therefore, the resolution of ethnic disparities in cardiovascular health. Successful strategies must include: 1) partnerships for long-term, sustainable, population-wide strategies on risk factor modification; 2) models of culturally competent health care delivery; and 3) research on the gene-environment interactions, which cause the susceptibility of ethnic minorities to cardiovascular disease. PMID- 11763310 TI - Detection of t(I 1; 18) in MALT-type lymphoma with dual-color fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction analysis. AB - t(11:8) is a recurrent chromosomal abnormality observed in mucosa-associated lymphoid tissue (MALT)-type lymphoma. API2 and MLT genes have been implicated. The authors devised a dual-color interphase fluorescence in situ hybridization (FISH) system to detect splitting of 11q22 and its fusion with 18q21. Subjects were 44 cases of extranodal lymphoma and cases of primary macroglobulinemia. Whenever RNA was available, reverse transcriptase-polymerase chain reaction followed by sequence analysis was performed. Positive cases by dual-color FISH analysis were restricted to MALT-type lymphoma and one case of primary macroglobulinemia. Among 24 cases of MALT-type lymphoma, 14 (58%) (4 gastric, 5 pulmonary, 3 orbital, 1 salivary, and 1 thyroid lymphomas) had splitting of the 11q22 region probes and fusion of signals suggesting the translocation of chromosome 11 and 18. Reverse transcriptase-polymerase chain reaction analysis showed the API2/MLT gene fusion in 9 of 10 cases. Sequence analyses showed three different modes of involvement of the MLT gene, whereas the breakpoint at API2 was the same. Monoclonal component of serum immunoglobulin M was observed in 3 of 14 positive cases for the translocation. Direct visualization using dual-color FISH on samples serves as a molecular tool for management of MALT-type lymphoma with API2/MLT gene fusion. PMID- 11763311 TI - Use of novel t(11;14) and t(14;18) dual-fusion fluorescence in situ hybridization probes in the differential diagnosis of lymphomas of small lymphocytes. AB - Increasingly, molecular biologic techniques have become important in the diagnosis of non-Hodgkin lymphomas. In the differential diagnosis of lymphoma(s) of small lymphocytes (LSL), reliable detection of t(11;14) or t(14;18) would confirm the diagnosis of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL), respectively. A total of 87 LSL cases (27 MCL, 39 FCL, 17 small lymphocytic lymphoma [SLL], 3 marginal zone lymphomas, and 1 paraimmunoblastic variant of SLL) were diagnosed by a combination of light microscopy, immunohistochemistry, and flow cytometric immunophenotyping. Interphase fluorescence in situ hybridization (FISH) for t(11;14) and t( 14;18) using dual fusion probes (Vysis, Downers Grove, IL) was performed on touch (n = 69) or gravity (n = 18) preparations from these cases. Of 27 MCL cases tested, 25 (93%) had demonstrable t(11;14), none had t(14;18), and 2 were negative for t(11;14) and t(14;18). Twenty-five of 39 (64%) FCL cases had t(14;18), none had t(11;14), and the remaining FCL cases (14 cases [35%]) had neither t(11;14) nor t(14;18). All 17 (100%) SLL cases had neither t(11;14) nor t(14;18). All 3 (100%) marginal zone lymphoma cases had neither t(11;14) nor t(14;18). The case of paraimmunoblastic variant of SLL had t(11;14) and was negative for t(14;18). No discrepant [i.e., positive for both t(11;14) and t(14;18)] or false-positive cases were noted. Interphase FISH using these commercially available probes is a useful adjunct to light microscopy, immunohistochemistry, and flow cytometric immunophenotyping in the diagnosis of LSL. FISH can be performed successfully on archival single-cell preparations (touch preparations or gravity preparations) when fresh tissue is unavailable. No discordant or false-positive cases were identified. PMID- 11763312 TI - Chromosome 11 copy number gains and Epstein-Barr virus-associated malignancies. AB - Epstein-Barr virus (EBV) genome can be found in many malignant tumors in China. Previous data of interphase cytogenetics, by comparative genomic hybridization and/or fluorescence in situ hybridization, on nasopharyngeal carcinomas and natural killer cell-type non-Hodgkin lymphomas in Hong Kong have noted gains in chromosome 11. This study compares the frequency of chromosome 11 copy number gains in three different types of EBV-associated tumors in Hong Kong. Using alpha satellite probes, the authors studied by fluorescence in situ hybridization 31 EBV-positive tumors comprising 10 EBV-positive gastric carcinomas, 8 lung lymphoepithelioma-like carcinomas, and 13 non-Hodgkin lymphomas. Trisomy or polysomy 11 was detected in 10 of 10 (100%) EBV-positive gastric carcinomas, 6 of 8 (75%) lung lymphoepithelioma-like carcinomas, and 4 of 13 (30.8%) non-Hodgkin lymphomas. Compared with the EBV-positive gastric carcinomas, the 10 EBV-negative gastric carcinomas that were also studied showed chromosome 11 copy number gains in 3 of 10 (30%), a significantly lower frequency. The authors conclude that gains in chromosome 11 are common in EBV-associated malignancies in Hong Kong, with the strongest association found in gastric carcinoma. There seems to be differences between EBV-associated tumors of different locations, and between gastric carcinomas with and without EBV. PMID- 11763313 TI - Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes. AB - Chondrosarcomas are malignant cartilaginous tumors. Most are located in the medullar cavity (central chondrosarcoma), and a minority develop in a preexisting osteochondroma (peripheral chondrosarcoma). The authors present karyotypes for 37 central, peripheral, juxtacortical, and dedifferentiated chondrosarcomas. Using loss of heterozygosity (LOH) analysis and DNA flow cytometry, the authors previously showed that central and peripheral chondrosarcomas probably evolve by different genetic mechanisms. Peripheral chondrosarcoma is characterized by genetic instability, as was previously shown by a high percentage of LOH and a broad range in DNA ploidy. The authors now show that all peripheral chondrosarcomas tested are aneuploid, combined with many nonspecific chromosomal aberrations. Two juxtacortical chondrosarcomas showed normal chromosome numbers combined with limited structural alterations, substantiating that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic background. Central chondrosarcomas were previously found to be peridiploid with limited LOH, most frequent at 9p21. In the current study, chromosome 9 was involved in five of seven central chondrosarcomas compared with only one of four peripheral chondrosarcomas. Three central tumors showed involvement of the 9pl2-22 region, suggesting an important role for chromosome 9 in the oncogenesis of central chondrosarcoma. Moreover, trisomy 22 was found in four central chondrosarcomas only. PMID- 11763314 TI - Expression of fas ligand in metastatic prostatic carcinoma: suggestive of possible clonal expansion of subpopulation with metastatic potential. AB - Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases. Analysis of the FasL gene and its mRNA by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively, suggested that the expression of immunohistochemically detectable FasL in metastatic tumor cells was not due to mutation in the FasL gene with resulting overexpression. Further, FasL expression was detectable in the acinar epithelial cells of prostates with morphologic atrophic changes, suggesting that FasL also plays a role in the physiologic apoptosis process of noncancerous prostate. The current data suggest that a subpopulation of prostate carcinoma cells clonally expresses FasL, and this subpopulation may have metastatic potential. Evaluation of FasL expression in the primary tumor thus may provide a useful parameter for predicting metastatic potential of the tumor. PMID- 11763315 TI - Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia. AB - Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disease characterized by mild hypercalcemia, an inappropriately high parathyroid hormone level, and absence of hypercalciuria. Heterozygous inactivating mutations of calcium-sensing receptor (CaSR) are found in about two thirds of patients with FHH. Histologic examination of parathyroid glands in FHH is reported to show normal histology or chief cell hyperplasia. Thus, histologic features of the parathyroid glands in FHH vary, and there is no clear histologic criterion that indicates FHH. The authors have encountered three hypercalcemic patients with characteristic histologic features of enlarged parathyroid glands. Clusters of parenchymal cells were mixed with fat cells, and the area of fat cells was 33% to 49% of the total area. These features are similar to those described as parathyroid lipohyperplasia. Postoperative evaluation showed that fractional excretion of calcium was low in these patients. Direct sequencing of the polymerase chain reaction product showed that the first patient was heterozygous for an already reported inactivating mutation of CaSR (P55L). The second patient was also heterozygous for a novel inactivating mutation (R220W). The third was homozygous for an inactivating mutation (Q27R). These results indicate that histologic features of parathyroid lipohyperplasia suggest the presence of inactivating mutations of CaSR. PMID- 11763316 TI - Expression of ID genes in differentiated elements of human male germ cell tumors. AB - The ID genes are members of a family of genes that encode helix-loop-helix (HLH) containing proteins. The Id proteins, unlike other HLH proteins, lack an adjacent DNA binding domain and hence act as dominant negative regulators of HLH transcription factors that have been implicated in control of cellular differentiation. Although the role of Id genes in murine development has been documented, their roles in human embryogenesis remain unknown. In this study, human male germ cell tumors (GCTs) were used as a model for examining the expression of the ID genes in various histologies that are reflective of different temporal phases of human development. In seminomas, little or no expression of IDI, ID2, and ID3 was detected, consistent with the uncommitted germ cell-like phenotype of this tumor histology. Likewise, GCTs with histologies reflective of extraembryonic and embryonic patterns of differentiation exhibited patterns of expression of the three ID genes often similar to those noted during murine development. It was also evident, as revealed by ID expression patterns, that despite the overall aberrant spatial differentiation patterns displayed by these tumors, some tissue-tissue interactions reminiscent of those observed during normal embryogenesis are retained. Thus, adult male GCTs offer a unique system in which the role of genes such as the IDs can be studied in human embryogenesis. PMID- 11763317 TI - Analytic validation of a competitive polymerase chain reaction assay for measuring Epstein-Barr viral load. AB - Epstein-Barr virus (EBV) is associated with several benign and malignant diseases, and blood tests for EBV viral load show promise as markers of disease burden in affected patients. A commercial quantitative PCR method (BioSource International) was recently introduced to facilitate measuring viral load. It relies on coamplification of EBV DNA and a spiked competitor in plasma or serum, followed by semiautomated product detection on enzyme-linked immunosorbent assay (ELISA) plates. In the current study, analytic performance characteristics were assessed, and the authors describe several methodologic improvements to facilitate laboratory implementation. Rapid DNA extraction was accomplished using commercial silica spin columns, heat-labile uracil-N-glycosylase was used to inhibit amplicon contamination, and inexpensive agarose gels were used to screen for polymerase chain reaction products requiring ELISA plate quantitation. Accuracy and precision were verified using EBV DNA standards derived from two cell lines and plasmid containing viral sequences. The assay was sensitive to as few as five template copies per polymerase chain reaction and was linear across four orders of magnitude (correlation coefficient 0.995). When applied to matched plasma and serum samples from 15 patients with nasopharyngeal carcinoma, both sample types yielded similar viral load results. This commercial EBV viral load assay provides sensitive and quantitative detection of EBV DNA using equipment already available in many molecular diagnostic laboratories. PMID- 11763318 TI - Comparison of the DNA extraction methods for polymerase chain reaction amplification from formalin-fixed and paraffin-embedded tissues. AB - To obtain an adequate quality and quantity of DNA from formalin-fixed and paraffin-embedded tissue, six different DNA extraction methods were compared. Four methods used deparaffinization by xylene followed by proteinase K digestion and phenol-chloroform extraction. The temperature of the different steps was changed to obtain higher yields and improved quality of extracted DNA. The remaining two methods used microwave heating for deparaffinization. The best DNA extraction method consisted of deparaffinization by microwave irradiation, protein digestion with proteinase K at 48 degrees C overnight, and no further purification steps. By this method, the highest DNA yield was obtained and the amplification of a 989-base pair beta-globin gene fragment was achieved. Furthermore, DNA extracted by means of this procedure from five gastric carcinomas was successfully used for single strand conformation polymorphism and direct sequencing assays of the beta-catenin gene. Because the microwave-based DNA extraction method presented here is simple, has a lower contamination risk, and results in a higher yield of DNA compared with the ordinary organic chemical reagent-based extraction method, it is considered applicable to various clinical and basic fields. PMID- 11763319 TI - Rotary International: a partner in polio eradication. AB - Rotary International remains committed to the goal of global eradication of polio and certification by 2005. The reports of possible sources of virulent vaccine derived poliovirus, which may persist after the global eradication of wild poliovirus, need to be investigated rapidly. If these sources are confirmed to be significant risks to global polio eradication, methods to eliminate these sources need to be identified and implemented. Final recommendations on the stopping of vaccination need to be made by WHO. PMID- 11763320 TI - Will the polio niche remain vacant? AB - C-Cluster enteroviruses (C-CEVs), consisting of Coxsackie A viruses (C-CAV1, 11, 13, 15, 17, 18, 19, 20, 21, 22, 24, 24v) and polioviruses (PV1, 2, 3), have been grouped together in relation to their genomic sequences. On the basis of disease syndromes caused in humans, however, C-CAVs and PVs are vastly different: the former cause respiratory disease, just like the major receptor group rhinoviruses (magHRV), whereas PVs, on invasion of the CNS, can cause poliomyelitis. It is assumed that the difference in pathogenesis of C-CEVs is governed predominantly by cellular receptor specificity. C-CAVs use ICAM-1, just like magHRV, whereas PVs uniquely use CD155. Both ICAM-1 and CD155 are Ig-like molecules. Remarkably, based on a phylogenetic analysis of non-structural proteins, CAV 11, 13, 17 and 18 are interleaved with, rather than separated from, the three PV serotypes, e.g. PV1 is more closely related to CAV18 that to PV2. This observation suggests that PVs may have emerged from a pool of C-CAVs by evolving a unique receptor specificity. We have been studying virion structure, virion/receptor interactions, genetics, and the molecular biology of C-CEVs with the objective of identifying the molecular basis of phenotypic diversity of these viruses. Of particular interest is the prospect that C-CEVs can be genetically manipulated to switch their receptor affinity: from CD155 to ICAM-1 for PVs, or from ICAM-1 to CD155 for C-CAVs. We propose a hypothesis that in a world free of poliovirus and anti-poliovirus neutralizing antibodies C-CAVs would be given a greater chance to switch receptor specificity from ICAM-1 to CD155 and thus, to evolve gradually into a new polio-like virus. PMID- 11763321 TI - The eradication of foot-and-mouth disease: a parallel problem. AB - Poliomyelitis and foot-and-mouth disease (FMD) can both be prevented by vaccination. The vaccines are highly effective but they differ in that, whereas in most countries attenuated viruses have been used to control poliomyelitis, FMD vaccines are prepared from the virulent viruses. The reasons for choosing inactivated vaccines for FMD are (i) the demonstration several decades ago that a virus which was attenuated for one species could be virulent for another and (ii) the great antigenic variability of the virus. This has meant that the viruses to be used for vaccination have to "match" those occurring in the field. It also means that they should only be handled under strict conditions of containment. PMID- 11763322 TI - Stopping a polio outbreak in the post-eradication era. PMID- 11763323 TI - Possible global strategies for stopping polio vaccination and how they could be harmonized. AB - One of the challenges of the polio eradication initiative over the next few years will be the formulation of an optimal strategy for stopping poliovirus vaccination after global certification of polio eradication has been accomplished. This strategy must maximize the benefits and minimize the risks. A number of strategies are currently under consideration, including: (i) synchronized global discontinuation of use of oral poliovirus vaccine (OPV); (ii) regional or subregional coordinated OPV discontinuation; and (iii) moving from trivalent to bivalent or monovalent OPV. Other options include moving from OPV to global use of IPV for an interim period before cessation of IPV use (to eliminate circulation of vaccine-derived poliovirus, if necessary) or development of new OPV strains that are not transmissible. Each of these strategies is associated with specific advantages (financial benefits for OPV discontinuation) and disadvantages (cost of switch to IPV) and inherent uncertainties (risk of continued poliovirus circulation in certain populations or prolonged virus replication in immunodeficient persons). An ambitious research agenda addresses the remaining questions and issues. Nevertheless, several generalities are already clear. Unprecedented collaboration between countries, regions, and indeed the entire world will be required to implement a global OPV discontinuation strategy Regulatory approval will be needed for an interim bivalent OPV or for monovalent OPV in many countries. Manufacturers will need sufficient lead time to produce sufficient quantities of IPV Finally, the financial implications for any of these strategies need to be considered. Whatever strategy is followed it will be necessary to stockpile supplies of a poliovirus-containing vaccine (most probably all three types of monovalent OPV), and to develop contingency plans to respond should an outbreak of polio occur after stopping vaccination. PMID- 11763324 TI - Progress with inactivated poliovirus vaccines derived from the Sabin strains. AB - To produce a safe and effective inactivated poliovirus vaccine (IPV), we have developed S-IPV using Vero cells infected with the Sabin strains in a semi production scale. All production steps including virus culture on microcarrier beads were highly reproducible. Mean recovery percents of infectious viruses or D antigens during all processes for concentration, purification and inactivation were 30-50% in the three types. The S-IPV potency was adjusted for D-antigen content as determined by in-house ELISA and was comparable to WHO reference IPV derived from the virulent strains in immunogenicity tests in rats. Antibody development in more than 30 seronegative infant volunteers after two shots of S IPV at four-week interval were 100% without notable adverse reactions. The mean antibody titres (log2) to Sabin 1, 2 and 3 viruses were 11.1, 8.3 and 8.9, respectively. The antibodies neutralized the Mahoney, MEF-1, and Saukett virulent strains with slightly inferior titres to those of the Sabin strains. D-antigens for each type of S-IPV were stable at 4 degrees C without any significant decrease over more than two years. PMID- 11763325 TI - Inactivated vaccines based on alternatives to wild-type seed virus. PMID- 11763326 TI - Live-attenuated strains of improved genetic stability. AB - The current live-attenuated vaccine strains of poliovirus are genetically unstable and capable of rapid evolution in human hosts, resulting in reversion to neurovirulence and, occasionally, disease. They can also be shed by recipients for a considerable time after vaccination. This raises questions about how and when to stop vaccination after wild-type viruses have been eliminated. Persistence of vaccine revertant viruses in the population would present a risk to new cohorts of unvaccinated children and threaten the success of the eradication programme. A number of Sabin vaccine strain derivatives have been described that are, in theory, genetically more stable than the present vaccines and therefore less likely to revert to virulence. The approaches used in their derivation are outlined here and data presented for two strains showing a significant improvement in genetic stability. These strains were designed according to our understanding of the molecular basis of attenuation and incorporate changes in the sequence of an RNA structural domain that plays a key role in attenuation. They may also be less transmissible than the current type 3 vaccine strain and are potentially useful in the strategically difficult final stages of poliomyelitis eradication. PMID- 11763327 TI - Vaccines based on recombinant antigen strategies. PMID- 11763328 TI - Anomalous observations on IPV and OPV vaccination. AB - Anomalies of vaccine performance are events or observations that go counter to the current paradigms on the properties of a vaccine. In the current paradigm, inactivated poliovirus vaccine (IPV) induces serum immunity to protect the individual from poliomyelitis, but not mucosal immunity to prevent subsequent wild poliovirus infection. Therefore, it is believed not to be suitable to interrupt virus transmission in polio-endemic tropical and developing countries, where poliovirus transmission is thought to be predominantly faecal-oral, unlike in countries with excellent sanitation, where it is predominantly respiratory. Oral poliovirus vaccine (OPV), because it is believed to mimic natural (wild) poliovirus infection and to induce serum and mucosal immunity, is considered ideal to interrupt virus transmission in countries with poor sanitation and endemic polio. Moreover, the vaccine viruses are shed in the stools and it is presumed to spread faeco-orally to unvaccinated children in the vicinity, thus increasing its effectiveness in the community. These paradigms on both vaccines may be seen in standard textbooks of virology and paediatrics. In reality, IPV induces very high mucosal immunity in a monkey model, lasting at least 12 months and providing complete protection against oral challenge with wild virus. In field trials, IPV has been found to have very high vaccine efficacy (VE) and to retard significantly wild-virus transmission in communities. OPV, requiring five to seven doses for individual protection, does not seem to induce effective mucosal immunity. Hence, 10-15 doses of OPV and near 100% vaccination coverage are necessary for interruption of virus transmission in countries with poor sanitation. In the monkey model, wild poliovirus infection did not offer any mucosal protection against a second infection, indicating that live virus infection is not the best way to induce mucosal immunity (unless repeated several times). The immunity induced by OPV has two arms, individual protection (by serum immunity) and mucosal protection from later infection by wild virus; these are dichotomous, as evidenced further by protected children participating in wild virus transmission in breakthrough outbreaks in communities well vaccinated with OPV. There is no evidence that polioviruses, wild or vaccine, spread faeco-orally to any meaningful extent. The median age of polio in India, in the pre-vaccine era, and even in recent years was 12-18 months. No other faeco-oral infection has such a low median age. Measles virus transmission is respiratory, and the median age of measles is over two years. Wild virus is shed faecally, but by the age when faecal microbes infect children, most of them are already immune to disease caused by polioviruses. As for vaccine viruses, even when heavy inocula are fed repeatedly, children may not always become infected. That exposure to the small amounts of virus through faecal contamination (unlike microbes that multiply in food) would infect them, is an unrealistic expectation. There are sufficient anomalies demanding our revision of the old paradigms. IPV is a better immunogen than OPV and is completely safe. During the interval between the cessation of wild virus transmission and the global stoppage of polio vaccination, it will be advantageous to use IPV, particularly combined with DPT vaccine, to provide individual protection, and herd effect to prevent spread in case of the introduction of wild polioviruses, whether unintentionally or otherwise, and to bolster the Expanded Programme on Immunisation. PMID- 11763329 TI - The efficiency and reliability of polio surveillance. AB - Surveillance for acute flaccid paralysis (AFP) in children younger than 15 years, and careful investigation of the cases, are the cornerstones for monitoring the progress of the poliomyelitis eradication programme. However, its sensitivity to detect wild type poliovirus (wtPV) circulation decreases when the incidence of true polio cases approaches zero. Under these conditions, only about one in 100,000 children is being investigated for poliovirus excretion. No real alternative approach which is generally exploitable has been developed. Environmental surveillance may in optimal conditions be at least as sensitive in detecting poliovirus circulation as AFP surveillance. However, optimal conditions, i.e. converging sewage systems, are not used by most people in the remaining endemic countries. Enterovirus surveillance, based on isolation of poliovirus in the routine diagnostic services, is only applicable in a few countries, where the diagnostic activity covers the entire population. Whichever approach is used, we will never reach 100% certainty of complete elimination of wtPV circulation. However, by applying all these approaches optimally, we may eventually reach a probability level allowing the safe cessation of immunisation. PMID- 11763330 TI - Evaluation of the new control methods for oral poliomyelitis vaccine. AB - In the draft recommendations for production and control of OPV the WHO proposed new control methods: (i) mutant analysis with PCR and restriction enzyme cleavage (MAPREC) assay that allows evaluation of poliovirus population heterogeneity at the molecular level; (ii) neurovirulence (NV) test using transgenic mice susceptible to polioviruses and (iii) control of the seed lots for the presence of the simian virus 40 (SV40) DNA sequence. This paper is focused on our experience in the practical implementation of the new methods at the Institute of Poliomyelitis and Viral Encephalitides (IPVE). Using methods based on PCR we have demonstrated that working seed viruses used by IPVE for OPV production are free from SV40 DNA sequences. Our experience on the conduction of the OPV type 3 control using TgPVR21 mice NV test (seven vaccine lots) and the MAPREC assay (more than 150 samples of single harvests and monovalent bulks) showed that these methods may be used instead of the monkey NV test, because they could not pass the vaccine failed monkey NV test. The necessity for single harvests control is discussed. PMID- 11763331 TI - Poliomyelitis in Russia in 1998-1999. AB - After introducing surveillance for poliomyelitis and AFP cases in the Russian Federation in 1998, 740 AFP cases have been registered in 1998-1999, and 18 of that number were considered as vaccine-associated paralytic poliomyelitis (VAPP). Of 18 cases 11 were classified as VAPP of vaccine recipients and confirmed by virus isolation; from two of the vaccine recipients virus was not isolated, and five were poliomyelitis cases in contact non-vaccinated children. In all the cases the disease was characterised with the typical clinical picture with residual pareses and paralyses. One case was fatal. Vaccine virus type 3 has been isolated from all the vaccine recipients. The MAPREC test has shown that the quality of monovaccine type 3 bulks used for vaccinating these children did not differ from the quality of other bulk vaccines produced by the Chumakov Institute of Poliomyelitis. Patients surveyed for gammaglobulin were positive. Polioviruses type 1 isolated from two of the contact cases had changed antigenic properties and were recombinants of types 1 and 2. PMID- 11763332 TI - Inhibition of poliovirus RNA synthesis as a molecular mechanism contributing to viral persistence in the mouse central nervous system. AB - Many survivors of poliomyelitis, several decades after the acute phase of the disease, develop a set of new muscle symptoms called post-polio syndrome. The persistence of poliovirus (PV) in the central nervous system (CNS) may be involved in the aetiology of this syndrome. By using a mouse model, we have shown that PV persists in the CNS of paralysed mice for over a year after the acute disease. Detection of PV plus- and minus-strand RNAs in the spinal cord of paralysed mice suggested continuous PV RNA replication in the CNS. However, infectious PV particles could not be recovered from homogenates of CNS from paralysed mice beyond 20 days post-paralysis, indicating that PV replication was restricted. In an attempt to identify the molecular mechanism by which PV replication was limited, PV plus- and minus-strand RNA levels were estimated in the CNS of persistently infected mice by a semi-quantitative RT-nested PCR method. Results revealed that RNA replication was inhibited at the level of plus strand RNA synthesis during persistent infection. Similar results were obtained in neuroblastoma IMR-32 cell cultures persistently infected with PV Restriction of PV RNA synthesis could be involved in persistence by limiting PV replication. PMID- 11763333 TI - Outbreak of paralytic poliomyelitis in the Chechen Republic in 1995. AB - An outbreak of poliomyelitis with 146 cases among children of whom six died occurred in the Chechen Republic in 1995. Sporadic cases of poliomyelitis have been reported in the neighbouring Ingush Republic. The outbreak lasted for five months (from May to September) and the maximum number of cases was registered in July. The age of the patients did not exceed 11 years, and more than 90% of the patients were children aged from one month to four years. The overwhelming majority of the patients had not been vaccinated in the routine OPV immunization programme. The outbreak was due to wild poliovirus type 1 belonging to genotype T previously known to circulate in the territory of the former Soviet Union (FSU). Chechen and Ingush isolates were very closely related to each other and to isolates from Central Asia, Tajikistan, 1994. Only a very distant relatedness of the Chechen and Ingush isolates was found with the strains isolated at about the same time outside the FSU (China 1994, Pakistan 1995). The presence of high numbers of non-vaccinated/poorly vaccinated persons and the poor sanitary and hygienic conditions for civilians due to the military conflict were factors that had a role in the outbreak. PMID- 11763334 TI - Progress towards global polio eradication. AB - In the 12 years since the global polio eradication goal was set in 1988, the eradication initiative has reached every polio-endemic country. Mass immunization campaigns have reached as many as 450 million children per year and 134 million children in a single day. The number of reported cases has declined from 35,251 to 7088 cases during that time span. Because surveillance has improved the decline in cases occurring is significantly greater. Wild poliovirus transmission is now confined to South Asia and West and Central Africa and the Horn of Africa. Although significant obstacles remain, it appears likely that polio will be eradicated world-wide by the end of the year 2002. PMID- 11763335 TI - A scenario for polio eradication. AB - Polio eradication has entered the phase operating in the Asian sub-continent and in sub-Saharan Africa, where polio is still endemic in 30 countries. These countries are apparently most resistant to the eradication effort. The WHO polio panel held in May, in Geneva, discussed a scenario to stop transmission by 2002 and thereafter three years for certification. This paper discusses the scenario based on experience with smallpox eradication from the viewpoint of impact of population density on immunisation. The programme in the Indian sub-continent, which has the world's highest population density, may require a more rigorous surveillance-containment type strategy than that in sub-Saharan Africa which, with its lower density of population in many countries, may be relatively susceptible to the eradication effort. However, countries with higher population density and/or with political trouble may pose substantial difficulties. Also briefly discussed are measures to be taken after interruption of polio transmission world-wide. These still require intensive studies. The goal is foreseeable and with intensified mobilisation of global resources. PMID- 11763336 TI - Some problems of molecular biology of poliovirus infection relevant to pathogenesis, viral spread and evolution. AB - Molecular mechanisms of poliovirus reproduction in the human gut remain largely unexplored. Nevertheless, there are grounds to believe that the virus spreads from cell to cell, like that from person to person during natural circulation, and involves a relatively small proportion of the highly heterogeneous viral population generated by the previous host. This mechanism of random sampling is responsible for the majority of fixed mutations, and contributes to the maintenance of a certain level of viral fitness (virulence). In the long term, random sampling may lead to the decrease in fitness and even to extinction of some viral evolutionary branches, explaining cases of self-limiting poliovirus infection in immunodeficient patients. A low propensity of the Sabin viruses for natural circulation may also be a related phenomenon. The trend to decrease in fitness may be interrupted by the appearance of rare, fitter (more virulent) variants, which may be responsible for poliomyelitis outbreaks caused by wild type virus, and for the development of paralytic disease in chronic carriers of the Sabin vaccine. All these evolutionary events are largely stochastic and hence are unpredictable in principle. PMID- 11763337 TI - The molecular basis of poliovirus neurovirulence. AB - Species specificity of poliovirus (PV) is mostly governed by host cellular molecules that serve as the PV receptor (PVR). Molecular cloning of the gene and cDNAs of human PVR and the subsequent development of PV-sensitive transgenic (Tg) mice carrying the human PVR gene made it possible to investigate molecular mechanisms for PV-specific dissemination in the whole body. After intravenous inoculation which makes artificial viremia, poliovirus appears to enter the central nervous system (CNS) at a fairly high rate via the blood brain barrier, suggesting existence of a specific permeation system for PV. This main dissemination process does not require PVR. After intramuscular inoculation, PV appears to be incorporated by endocytosis at synapses, and the endosomes containing PV transported through axons to neuron cell body, where viral replication occurs. Efficiency of viral multiplication in the CNS probably determines the neurovirulence level, which differs between PV strains. An important determinant for neurovirulence phenotype resides in the internal ribosomal entry site (IRES). This has led us to a concept of "IRES-dependent virus tropism". PMID- 11763338 TI - Strengths and weaknesses of current polio vaccines--a view from industry. AB - Polio eradication is within our grasp and, unless something terribly wrong and unexpected happens, the three types of wild polioviruses will cease to circulate in human populations within the next few years. This achievement will be a result of the rational use of OPV. A momentous global decision--discontinuation of vaccination--will then have to be taken. The most important uncertainty that will weigh upon that decision is whether wild polioviruses can re-emerge after "eradication" defined as "complete interruption of wild polioviruses transmission", has been obtained. It is important to realise that "eradication" does not mean "extinction" in the sense that the dodo is extinct. After eradication, wild polioviruses will still lurk in laboratory specimens and in protected environmental sites (like glaciers) and may even "re-emerge" by back mutation or recombination of Sabin-derived strains that may continue to circulate even after OPV use is discontinued. Theoretically, the risk of re-emergence of wild polioviruses would be lessened if IPV was used for a number of years to immunise all those born after cessation of OPV usage. But the question is "by how much?". Vaccination with IPV will reduce the risk that persistent OPV-derived strains (e.g. in immunodeficient patients) will have the chance to establish permanent transmission after vaccination is totally discontinued. However, the risk of re-emergence will not be changed since this will be determined by the risk of accidental re-introduction. Whether the expense of switching completely from OPV to IPV globally can be justified will depend upon the relative risks of wild poliovirus re-emergence from either OPV-derived sources or other environmental sources including "escape" of virulent seed viruses from IPV production facilities. This balance of probabilities and risks will be very difficult to determine. In any case, it is likely that the decision to upscale IPV production to required levels has already been delayed too long so that polio eradication will be achieved by the use of OPV in developed as well as in less developed countries that cannot afford to use IPV at a high enough vaccine coverage rate to make it safe. Wild poLiovirus transmission has been interrupted with OPV in the Western Hemisphere. There is no reason why this cannot be done in the rest of the world. In industrialized countries that can afford it and where vaccine coverage is sufficient to prevent wild virus circulation, IPV, in combined vaccines, will be increasingly used. Let us hope that politicians in developing countries and zealous ethicists in the developed world will understand why, in the present and foreseeable future circumstances, OPV is better than IPV in the poorer countries and will not demand, in the name of equity in health, a total switch to IPV. For eradication, IPV cannot, and hopefully need not, replace OPV. At this stage it should not. PMID- 11763339 TI - The scientific basis for stopping polio immunisation--issues and challenges. AB - Eradication of polio is in sight. Once this is finally achieved there is general agreement that the world should move from the current policy of universal childhood immunisation, mostly with the oral poliovirus vaccine (OPV), to no immunisation. The challenge ahead is to build consensus on how and when this is achieved. The major area of scientific uncertainty is whether OPV-derived strains excreted by vaccinees will establish chains of transmission in communities, especially in settings of poor hygiene, when population immunity levels begin to fall after immunisation ceases. Evidence from several sources suggests that this may not occur. Most convincing are studies that show polioviruses are not detected beyond three months after mass OPV campaigns in at least two countries that only use OPV in this way. However it is clear that there are significant gaps in our knowledge. These include the transmissibility of OPV-derived strains under certain ecological settings, the potential for persistently infected individuals to re-seed viruses into a community, and the molecular basis of transmissibility. Research in these areas is underway and will help develop and refine strategies for stopping polio immunisation. The potential risks and benefits of ceasing polio immunisation are such that the best available science is required to reach an informed decision. PMID- 11763340 TI - Characteristics of poliovirus strains from long-term excretors with primary immunodeficiencies. AB - Individuals who are deficient in humoral immunity are particularly at risk from infection with enteroviruses, and poliovirus in particular, where antibodies are the main source of protection from disease. Long-term excretion of vaccine strains of poliovirus has been documented for many years and instances of paralytic poliomyelitis in hypogammaglobulinaemic patients who were subsequently found to have been excreting virus for prolonged periods have been reported in the U.S.A., Germany and Japan. The identification of a healthy immunodeficient patient in the U.K. who has probably been excreting type 2 poliovirus for 15 years will be described, with the characteristics of the virus and the results of attempts at treatment so far. Such individuals pose a significant risk to the eradication programme unless they can be identified and treated. PMID- 11763341 TI - Risks of reintroduction of polio after eradication: the vaccine origin of an outbreak of type 3 poliomyelitis. AB - Sabin live-attenuated strains, which have proved to be the most effective tools for poliovirus eradication, could also be the source of reintroduction of polio epidemics after global eradication of wild poliomyelitis is achieved. There are still considerable gaps in our knowledge about the persistence of vaccine-derived viruses in the population and the mechanisms involved in poliovirus transmissibility, both of which are essential factors in assessing the risks posed by such strains and in designing effective strategies for the cessation of polio immunisation. In this report, we have examined virological and epidemiological aspects of an epidemic of poliomyelitis in 1968 in Poland that was shown to be associated with the use of the USOL-D-bac live-attenuated vaccine strain. Possible causes of the origin and progress of the outbreak included the pattern of virus excretion from vaccinees, mutations identified in epidemic viruses and the unique vaccination policies in Poland during the years preceding the epidemic. PMID- 11763342 TI - Progress towards polio eradication: an African perspective. AB - Despite daunting competing health priorities, Africa has made significant progress in polio control. Northern and Southern Africa appear to be polio-free and may shortly be certified as such; however, polio still remains endemic in West and Central Africa and the Horn of Africa. Countries "in difficult circumstancess", wracked by major civil wars, have particularly low routine vaccine coverage, although NIDS have been carried out during negotiated days of tranquillity. AFP surveillance has also improved, although the quality of stool specimens is still far from ideal. There is, nevertheless, an extraordinary political commitment to the eradication campaign. Lessons from the history of polio in the continent need to be heeded in designing end-game strategies. Obstacles on the path to successful eradication are undoubtedly more formidable on the African continent--perhaps the most serious of all are the continuing wars. International political commitment and focussed and empowering developmental aid are urgently needed. PMID- 11763343 TI - Neurovirulence of Sabin 1-derived polioviruses isolated from an immunodeficient patient with prolonged viral excretion. AB - We have analysed the neurovirulence of Sabin 1-derived isolates which persisted more than nine years in an immunodeficient patient in the U.S.A. Samples were collected from stool specimens at days 11 (St1), 23 (St2), 48 (St3), 126 (St5), and 200 (St7) after the onset of paralysis. Critical nucleotides associated with the reversion of virulence were examined. All the isolates had the substitutions at nucleotide positions 480 (G to A) in the 5'-non-coding region (NCR), 2438 (A to U) in VP3, 2795 (A to G) in VP1, and 6203 (C to U) in 3D. Serially diluted samples were injected intracerebrally to transgenic mice harbouring the human poliovirus receptor gene. Samples St2, 3, 5 and 7 showed typical virulent characters in transgenic mice, whereas the sample ST1 showed intermediate neurovirulence. It seemed that there were two variant viruses providing for a major (M) and a minor (m) populations. After disappearance of the m-variant, samples obtained at the later stages showed neurovirulence almost equivalent to that of the Mahoney strain. Thus, the Sabin 1 strain evolved towards full neuropathogenicity after long-term replication in humans by accumulating mutations. Therefore, OPV-vaccination of immunodeficient persons should be avoided. PMID- 11763344 TI - Poliovirus persistence in human cells in vitro. AB - Poliovirus (PV) can persist in vivo in the intestine of immunocompromised hosts for years. Moreover, immunocompetent individuals who have survived paralytic poliomyelitis sometimes develop the post-poliomyelitis syndrome (PPS), consisting of a variety of symptoms including new muscular atrophies. PPS may be due to PV persistence. We have developed models of PV persistence in neural cells and epidermoid cells. Cell determinants are of crucial importance for the establishment of persistent infections in human neuronal cells, whereas viral determinants play the primary role in human epidermoid HEp-2 cells. The results obtained with these in vitro models show the capacity of PV to persist and reveal a virus and cell co-evolution involving PV-receptor interactions. In addition, they suggest that several mechanisms are used by PV to establish and maintain persistent infections. PMID- 11763345 TI - Selection and characterization of active hammerhead ribozymes targeted against cyclin E and E2F1 full-length mRNA. AB - Proliferation of vascular smooth muscle cells is generally accepted as a key event in the development of restenosis following percutaneous transluminal angioplasty. To prevent human restenosis, we have designed a molecular strategy based on hammerhead ribozymes targeted against the mRNA of cyclin E and E2F1, two proteins relevant in cell cycle progression whose regulation is interconnected by a positive feedback loop. Following the identification of accessible ribozyme target sites by RNase H mapping, several hammerhead ribozymes were generated that cleave with comparable efficiency two different splice forms of cyclin E mRNA and the full-length and a truncated form of E2F1 RNA, respectively. The most active ribozymes were tested in vitro under single-turnover conditions yielding k(react)/K(m) ratios between 36 and 73 x 10(4) M(-1) min(-1), which places them in the top range ribozymes targeted against long and structured substrates. In addition, we show that the most active ribozyme selected in vitro reduces specifically and significantly (p < 0.0028) proliferation of cultured human vascular smooth muscle cells (VSMC). PMID- 11763346 TI - Inhibition of GM-CSF/IL-3/IL-5 signaling by antisense oligodeoxynucleotides targeting the common beta chain of their receptors. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 play a key role in allergic inflammation. They mediate their effect via receptors that consist of two distinct subunits, a cytokine-specific alpha subunit and a common beta subunit (betac) that transduces cell signaling. We sought to down-regulate the biologic activities of GM-CSF, IL-3, and IL-5 simultaneously by inhibiting betac mRNA expression with antisense technology. Experiments were performed with TF-1 cells (a human erythroleukemia cell line expressing GM-CSF, IL-3, and IL-5 receptors, which proliferates in response to these cytokines), monocytic U937 cells, which require these cytokines for differentiation, and purified human eosinophils. Cells were treated with antisense phosphorothioate oligodeoxynucleotides (ODN) targeting betac mRNA. In contrast to nontreated cells and cells treated by sense or mismatched ODN, antisense ODN inhibited betac mRNA expression and significantly decreased the level of cell surface betac protein expression on TF-1 and U937 cells. Receptor function was also affected. Antisense ODN were able to inhibit TF-1 cell proliferation in vitro in the presence of GM-CSF, IL-3, or IL-5 in the culture medium and eosinophil survival. We suggest that antisense ODN against betac may provide a new therapeutic alternative for the treatment of neoplastic or allergic diseases associated with eosinophilic inflammation. PMID- 11763347 TI - Inhibition of HIV-1 replication in vitro and in human infected cells by modified antisense oligonucleotides targeting the tRNALys3/RNA initiation complex. AB - The untranslated 5' leader region of the human immunodeficiency virus type 1 (HIV 1) RNA plays an essential role in retroviral replication. It is the first retrotranscribed RNA region, primed from a cellular tRNALys3 partially annealed to the HIV-1 primer binding site (PBS). The structural and functional features of the HIV-1 reverse transcription initiation complex have been thoroughly studied. In this work, we used chemically modified antisense oligonucleotides (AS-ODN) as competitors of the natural tRNALys3 primer for the PBS region. Modified 2'-O methyl AS-ODN were able to inhibit in vitro HIV-1 reverse transcription and displace the tRNALys3 previously annealed to the PBS. The destabilization of the initiation complex by 2'-O-methyl ODN was a sequence-specific process. We further demonstrated the importance of an anchor region contiguous to the PBS in the annealing of the antisense molecule, allowing the displacement of tRNALys3. The 20-mer 2'-O-methyl molecules were also able to inhibit viral replication in HIV-1 human infected cells, either by blocking cDNA synthesis during the early phase or by interfering with the annealing of the tRNALys3 primer to the PBS during the late phase of the viral cycle. Thus, the highly conserved retroviral initiation complex was shown to be a promising target when using the antisense strategy. PMID- 11763348 TI - Inhibition of Vesivirus infections in mammalian tissue culture with antisense morpholino oligomers. AB - Caliciviruses infect and cause disease in animals and humans. They are nonenveloped, positive-stranded RNA viruses with a genome of approximately 7.5 kb that encodes viral proteins in three open reading frames (ORF). Antisense oligomers targeting one of the three ORF of caliciviruses of the genus Vesivirus significantly inhibit viral replication in tissue culture. Porcine kidney and African green monkey kidney cells were infected with Vesivirus isolates SMSV-13 and PCV Pan-1. Phosphorodiamidate morpholino oligomers (PMO) with sequence complementary to the AUG translation start site regions of ORF1, ORF2, and ORF3 were evaluated for their effect on viral titer. Scrape-loading delivered PMO to 50%-70% of the cells of the two cell lines, as measured by fluorescence microscopy and flow cytometry. A PMO targeting ORF3 caused a significant increase in viral titer. A PMO targeting ORF2, a scrambled PMO control sequence, and an unrelated PMO antisense sequence did not alter viral titer. Various PMO sequences antisense to an upstream region of ORF1 were effective in reducing viral titer up to 80% in a dose-dependent and sequence-specific manner. The extent of viral titer reduction was proportional to the delivery of PMO to cells. These observations demonstrate that antisense PMO can disrupt caliciviral gene function in a nucleic acid sequence-specific manner and are potentially effective antiviral agents. PMID- 11763349 TI - High-level multiplex DNA amplification. AB - We present data on efficient amplification of large number of DNA targets using a single-tube polymerase chain reaction (PCR). This is a further enhancement of our approach to multiplexed PCR based on PCR suppression, which allows multiple DNA amplification using only one sequence-specific primer per amplicon while the second primer is common for all targets (Broude, N.E., et al., Proc. Natl. Acad. Sci. USA 98, 206-211, 2001). The reaction conditions have been optimized for simultaneous synthesis of 30 DNA targets, mostly consisting of fragments containing single nucleotide polymorphisms (SNP). The size of the amplified fragments, derived from many different human chromosomes, varies from 100 to 600 bp. We conclude that this method has potential for highly multiplexed DNA amplification useful for SNP analyses, DNA diagnostics, and forensics. PMID- 11763350 TI - CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved. AB - Oligodinucleotides containing CpG motifs stimulate vertebrate immune cells in vitro, have proven efficacy in murine disease models and are currently being tested in human clinical trials as therapies for cancer, allergy, and infectious disease. As there are no known immunostimulatory motifs for veterinary species, the potential of CpG DNA as a veterinary pharmaceutical has not been investigated. Here, optimal CpG motifs for seven veterinary and three laboratory species are described. The preferential recognition of a GTCGTT motif was strongly conserved across two vertebrate phyla, although a GACGTT motif was optimal for inbred strains of mice and rabbits. In a subsequent adjuvanticity trial, the in vitro screening methodology was validated in sheep, representing the first demonstration of CpG DNA efficacy in a veterinary species. These results should provide candidate immunostimulant and therapeutic drugs for veterinary use and enable the testing of CpG DNA in large animal models of human disease. PMID- 11763351 TI - Delivery of a hammerhead ribozyme specifically downregulates mutant type I collagen mRNA in a murine model of osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a systemic heritable disorder of connective tissue, caused by a mutation in one of the genes for type I collagen, whose cardinal manifestation is bone fragility. Several studies have identified two molecular mechanisms of collagen type I defects. In chain exclusion, the mutant chain is not incorporated into the collagen triple helix, whereas in chain nonexclusion, it is. The dominant-negative effect of nonexcluded mutations must be taken into account in all strategies aimed at correcting the collagen defects in individuals affected with moderate or several OI. Herein, we describe the application of hammerhead ribozymes to selectively target the mutant minigene transcript expressed in a murine calvarial osteoblast cell line. Active and control inactive ribozymes were tested in vitro on both mutant and normal targets and in the minigene-expressing cell line. Active ribozyme cleaved its target with high efficiency and specificity in both a time-dependent and dose-dependent manner. After delivery of a ribozyme expression construct, intracellular ribozyme was detected, along with a relative reduction in mutant transcript level. PMID- 11763352 TI - Gene expression profiles for monitoring radiation exposure. AB - Previous demonstrations that the dose, dose rate, radiation quality, and elapsed time since ionising radiation exposure result in variations in the response of stress genes suggest that gene expression signatures may be informative markers of radiation exposure. Defining sets of genes that ate specific for different outcomes of interest will be key to such an approach. A generalised post-exposure prolile may identify exposed individuals within a population, while more specific fingerprints may reveal details of a radiation exposure. Changes in gene expression in human cell lines occur after as little as 0.02 Gy rays, and in peripheral blood lymphocytes alter as little as 0.2 Gy. Diverse genes are also elevated in vivo in mice 24 h after 0.2 Gy irradiation. Ongoing microarray analyses meanwhile continue to identify large numbers of potential biomarkers from varied irradiation protocols. Development of computation-intensive informatics analysis methods will be needed for management of the complex gene expression profiles resulting from such experiments. Although the preliminary data are encouraging, significant work remains before meaningful correlations with risk or practical assessment of exposure can be made by gene expression profiling. PMID- 11763353 TI - Radiation exposure assessment using cytological and molecular biomarkers. AB - Chromosome aberration analysis is the conventional means of assessing radiation exposure. The Armed Forces Radiobiology Research Institute recently established an alternative method to measure radiation-induced chromosome aberrations in interphase cells. The method uses commercially available chemical agents to induce premature chromosome condensation in resting' G0 human peripheral blood lymphocytes. Then specific whole-chromosome DNA probes are used with fluorescence in situ hybridisation to detect aberrant cells rapidly over a broad dose range. In new research, the real-time fluorogenic 5'-nuclease, or TaqMan, polymerase chain reaction assay is being used to identify radiation-responsive molecular biomarkers, including gene expression targets and DNA mutations. The goal is to establish rapid, precise, high-throughput assay systems that are practical in a variety of radiation exposure scenarios. The new methodologies that have a number of other applications, together with diagnostic software now in development, could improve the United States military's emergency response capability and medical readiness. PMID- 11763354 TI - Base excision repair processing of radiation-induced clustered DNA lesions. AB - Energy from low LET ionising radiation, such as X rays and gamma rays, is deposited in the water surrounding the DNA molecule such that between 2 to 5 radical pairs are generated within a radius of I to 4 nm. As a result, multiple single lesions, including oxidised purine or pyrimidine bases, sites of base loss, and single-strand breaks, can be formed in DNA from the same radiation energy deposition event. The single lesions in these so-called multiply damaged sites or clustered lesions are repaired by base excision repair. Here we show that clustered DNA damages are formed in bacterial cells by ionising radiation and are converted to lethal double-strand breaks during attempted repair. In wild type cells possessing the oxidative DNA glycosylases that recognise and cleave DNA at repairable single damages, double-strand breaks are formed at radiation induced clusters during post-irradiation incubation and in a dose-dependent fashion. Mutant cells lacking these enzymes do not form double-strand breaks post irradiation and are substantially more radioresistant than wild type cells. These radioresistant mutant cells can be made radiosensitive by overexpressing one of the oxidative DNA glycosylases. Thus the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk. PMID- 11763355 TI - Clustered DNA damages as dosemeters for ionising radiation exposure and biological responses. AB - Clustered DNA damages--two or more lesions (oxidised bases. abasic sites, or strand breaks) within a few DNA helical turns on opposing strands--are induced in DNA in solution and in vivo in human cells by ionising radiation. They have been postulated to be difficult to repair, and thus of potentially high biological significance. Since the total of clustered damages produced by ionising radiation is at about 3 to 4 times higher levels than double-strand breaks and are apparently absent in unirradiated cells, levels of clustered damages present immediately alter radiation exposure could serve as sensitive dosemeters of radiation exposure. Since some clusters may not be repairable and may accumulate in cells, they might also be useful as integrating dosemeters of biological effects of radiation damage. PMID- 11763356 TI - Biomarkers of exposure and dose: state of the art. AB - Biomarkers provide methods to measure changes in biological systems and to relate them to environmental insults and disease processes. Biomarkers can be classified as markers of exposure and dose, markers of sensitivity, and markers of disease. It is important that the differences and applications of the various types of biomarkers be clearly understood. The military is primarily interested in early biomarkers of exposure and dose that do not require high levels of sensitivity but can be used to rapidly triage war fighters under combat or terrorist conditions and determine which, if any, require medical attention. Biomarkers of long-term radiation risk represent the second area of interest for the military. Biomarkers of risk require high sensitivity and specificity for the disease and insult but do not require rapid data turnaround. Biomarkers will help provide information for quick command decisions in the field, characterise long-term troop risks and identify early stages of radiation-induced diseases. This information provides major positive reassurances about individual exposures and risk that will minimise the physical and psychological impact of wartime radiation exposures. PMID- 11763357 TI - Validated biomarker responses influence medical surveillance of individuals exposed to genotoxic agents. AB - There is currently a vast armamentarium of biomarkers for evaluating human exposures to environmental carcinogens, the effects of such exposures and/or susceptibility to disease outcome. Before application, however, these biomarkers require validation in terms of truly reflecting what is claimed. Transitional epidemiological studies bridge the gap between laboratory and field. In a transitional study, a biomarker response is the dependent variable being evaluated, while the intended measure, i.e. exposure effect or susceptibility, is the independent variable. Once validated, biomarker responses provide valuable data for use in making human health risk assessments and as guides for individual medical surveillance programmes. An analysis of medical decision-making illustrates how biomarker responses that increase the relative risk of subsequent disease occurrence change the 'pre-test likelihood' of having the disease, thereby influencing interpretation of medical diagnostic tests and even the choice of tests to be performed. This argues that an individual's response using salidated biomarkers should be made part of the medical record. PMID- 11763358 TI - Fish cytogenetics and the future of radiation biodosimetry. AB - Fluorescence in situ hybridisation (FISH) with whole chromosome paints has greatly facilitated the analysis of structural chromosome aberrations and has led to translocations replacing dicentrics as the aberration of choice for many applications. Major challenges remain if we are to go from translocations to an understanding of the health consequences of radiation exposure. Yet to be surmounted are the roles of individual susceptibility, time since exposure, and the effects of subjects age. Accomplishing these objectives will require automation, reduced costs, improved calibration, and extensive use of baseline samples. PMID- 11763359 TI - Evaluation of three somatic genetic biomarkers as indicators of low dose radiation effects in clean-up workers of the Chernobyl nuclear reactor accident. AB - The goals of this study were to assess three biomarkers of genetic effect for their individual and collective ability to detect and estimate radiation exposure in Russian Chernobyl clean-up workers. Work assignments were planned to limit dose to 0.25 Gy. The three biomarkers employed were chromosome translocations detectcd in lynmphocytes by florescence in situ hybridisation (FISH), and mutation at two genes, glycophorin A (GPA) in red blood cells detected by flow cytometry and hypoxanthine phosphoribosyltransferase (HPRT) in lymphocytes detected by selective cell culture. Samples were Obtained from 1992 to 2000. The time between exposure at Chernobyl and sample acquisition was > or =5 years. The lymphocyte assays detected an elevation over controls in average outcomes it clean-up workers: translocation rates were 46% higher when adjusted for age and smoking and HPRT mutant frequencies were were 16% higher when adjusted for age. The G PA assay did not detect an exposure effect. The results indicate that measuring frequency of translocations by FISH is preferred for low dose radiation, retrospective biochemistry. PMID- 11763360 TI - Biomarkers specific to densely-ionising (high LET) radiations. AB - There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel. We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm anld inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. PMID- 11763361 TI - Recent insights into body weight control: from physiology to pathology. AB - Over the past several years, new modulators of feeding and body weight have been discovered, and our knowledge of the mechanisms and neurohumoral interactions between anorexigenic and orexigenic compounds has increased dramatically. This review aims to summarize the present knowledge of the role of leptin and several hypothalamic neuropeptides, such as neuropeptide Y (NPY), corticotropin-releasing hormone (CRH) and melanocortins, in the regulation of appetite and body weight. It also presents the progress made in the design of interactions between leptin and hypothalamic peptides in the regulation of feeding. The role of these compounds in the pathogenesis of obesity in animals and humans, and their potential usefulness in the treatment of this disorder, are discussed. PMID- 11763362 TI - Conformation of N-terminal HIV-1 Tat (fragment 1-9) peptide by NMR and MD simulations. AB - The N-terminal portion of HIV-1 Tat covering residues 1-9 is a competitive inhibitor of dipeptidyl peptidase IV (DP IV). We have used 1H NMR techniques, coupled with molecular dynamics methods, to determine the conformation of this peptide in the three diverse media: DMSO-d6, water (pH 2.7) and 40% HFA solution. The results indicate that in both DMSO-d6 and HFA the peptide has a tendency to acquire a type I beta-turn around the segment Asp5-Pro6-Asn7-IIe8. The N-terminal end is seen to be as a random coil. In water, the structure is best described as a left-handed polyproline type II (PPII) helix for the mid segment region Asp2 to Pro6. The structures obtained in this study have been compared with an earlier report on Tat (1-9). PMID- 11763363 TI - N-Terminal domain of HTLV-I integrase. Complexation and conformational studies of the zinc finger. AB - The HTLV-I integrase N-terminal domain [50-residue peptide (IN50)], and a 35 residue truncated peptide formed by residues 9-43 (IN35) have been synthesized by solid-phase peptide synthesis. Formation of the 50-residue zinc finger type structure through a HHCC motif has been proved by UV-visible absorption spectroscopy. Its stability was demonstrated by an original method using RP-HPLC. Similar experiments performed on the 35-residue peptide showed that the truncation does not prevent zinc complex formation but rather that it significantly influences its stability. As evidenced by CD spectroscopy, the 50 residue zinc finger is unordered in aqueous solution but adopts a partially helical conformation when trifluoroethanol is added. These results are in agreement with our secondary structure predictions and demonstrate that the HTLV I integrase N-terminal domain is likely to be composed of an helical region (residues 28-42) and a beta-strand (residues 20-23), associated with a HHCC zinc binding motif. Size-exclusion chromatography showed that the structured zinc finger dimerizes through the helical region. PMID- 11763365 TI - Gel-Phase synthesis of hydrophobic (thr14) (thr19) galanin (1 -19) fragment on a high capacity flexible crosslinked polystyrene support. AB - A hydrophobic analogue of human galanin (1-19) fragment has been synthesized using Boc/Bzl tactics to demonstrate the synthetic utility of the flexible crosslinked polystyrene support prepared by the suspension polymerization of styrene and 1,4-butanediol dimethacrylate. The copolymer was chloromethylated to 2.36 mmol Cl/g. The functionalized resin was found to possess all the physicochemical properties similar to Merrifield resin. The free peptide was obtained in high yield and purity as judged by RP-HPLC and characterized by amino acid analysis and ESI-MS. PMID- 11763364 TI - Discovery of potent and selective peptide agonists at the GRP-preferring bombesin receptor (BB2). AB - Analogues of the nonselective bombesin receptor synthetic agonist H-D-Phe-Gln-Trp Ala-Val-betaAla-His-Phe-Nle-NH2 were prepared and their biological activity assessed at the NMB-preferring/bombesin receptor (NMB-R: BB1), the GRP preferring/bombesin receptor (GRP-R: BB2) and the orphan receptor bombesin receptor subtype-3 (BRS-3; BB3). Progressive N-terminal deletions identified the minimum C-terminal sequences required for maintaining a significant agonist effect, whilst an alanine scan, targeted changes in stereochemistry and other pertinent substitutions identified key side-chain and stereochemical requirements for activation. Key structural elements required for functional potency at BB1 BB2 and BB3, and for selectivity between these receptor subtypes were established. Synthetic peptides were discovered. which were highly potent agonists at BB2 and extremely selective over both BB1 and BB3. PMID- 11763366 TI - Nursing ethics in an era of globalization. AB - We live in an era of globalization in which our essential interdependence is increasingly revealed. Transportation and communication technology plus worldwide health, environmental, and security risks and a world economy driven by transnational corporations are connecting us in a new kind of way. Incredible advances in biotechnology, the pressing demands of equity and justice in resource allocation, and the need for a universal perspective in health ethics are some of the issues challenging our moral imagination in significant ways. Nurses need to ask themselves: What changes for nursing ethics when the global-not the local becomes the dominant frame of reference? PMID- 11763367 TI - Reinvesting in social justice: a capital idea for public health nursing? AB - Social justice is a core ethical principle of public health nursing; yet, nurses' work as social activists has largely diminished over the past century. Reengagement in social justice activities is essential to change the current social, economic, and health differentials perpetuated by market justice ideologies. Social capital has emerged in the public health literature as a promising concept for developing community interventions that diminish disparities. Public health nurses, however, must be wary of uncritically adopting social capital as a panacea for inequalities; advocating for interventions seeking to build social capital may be as harmful as the inequalities themselves. PMID- 11763368 TI - Human biological materials in research: ethical issues and the role of stewardship in minimizing research risks. AB - Recent scientific and technologic advances generated from the human genome project have increased the ability of researchers to study human biological materials. This has enhanced the ease with which highly personal information such as genetic makeup can be revealed about individuals, families, and communities. In addition, a change in the societal value of human biological tissue from waste to commercial resource has occurred. A new model of stewardship is developed that can be used as a guide for protecting human research participants who are involved in studies that include collecting and handling human biological samples. Nursing implications to ensure protection of human research participants are discussed. PMID- 11763369 TI - Nursing with prisoners: the practice of caring, forensic nursing or penal harm nursing? AB - The number of incarcerated persons in the United States has been increasing dramatically over the last two decades. Incarcerated men and women have increased rates of serious and chronic physical and mental illnesses and therefore require substantial health care efforts. Caring for prisoners is a difficult and often unrewarding experience for health care providers, particularly within a social climate that encourages noncaring behaviors. This article critically analyzes three philosophic stances toward nursing care with prisoners and suggests their philosophic commensurability within traditional nursing practice. Implications for nursing practice, research, and education are discussed. PMID- 11763370 TI - Advancing nursing scholarship through the interpretation of imaginative literature: ancestral connectedness and the survival of the sufferer. AB - Imaginative literature has played an important role in nursing practice and education since the time of Florence Nightingale. Used primarily as an exemplar, however, its potential has not been realized fully by nurses. This article addresses the use of imaginative literature in scholarly inquiry. Often considered the aegis of literary critics and philosophers, the formal discipline of literary criticism enables the nurse to identify concepts and to generate theoretic explanations about human phenomena. The relationship between the ancestor and the survival of the sufferer is illustrated using Morrison's literary and cultural paradigm applied to selected novels. Implications for practice are identified. PMID- 11763371 TI - Chlamydial treatment failures: a persistent problem? PMID- 11763372 TI - What's new in pseudo-Kaposi's sarcoma. PMID- 11763373 TI - Rosacea fulminans. PMID- 11763374 TI - Unusual leucodermas. PMID- 11763375 TI - Laser tissue interaction in epidermal pigmented lesions. PMID- 11763376 TI - Skin disorders in the setting of renal failure: invited editorial. PMID- 11763377 TI - Role of Langerhans cells in the skin. What's new? PMID- 11763378 TI - Sexually transmitted infections and human immunodeficiency virus infection in Europe: the way ahead? AB - The incidence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) infection is increasing in Europe. The reasons for this are multifactorial but ease of travel is one of them. This is worrying in view of the established role of STIs in facilitating HIV transmission. Care of this group of infections is provided by a variety of doctors, often not following agreed guidelines. It is vital that doctors and their specialist societies engage in setting standards, in ensuring that STIs and HIV infection are moved up the healthcare agendas of all European countries and in making sure that access to care is rapid. Surveillance should be enhanced, interventions evaluated and the media engaged. PMID- 11763379 TI - Electron microscopic evidence of persistent chlamydial infection following treatment. AB - Chlamydia trachomatis infections of the female and male genital tracts are often asymptomatic and, thus, tend to become persistent. In the persistent state the typical Chlamydia life cycle is arrested and standard antibiotic regimens do not always eradicate this infection. We sought to relate treatment failures in men and women with persistent chlamydial genital tract infections to electron microscopic evidence of chlamydial persistence and with atypical morphological forms of the organism. Of 16 patients with chlamydial persistence following azithromycin treatment, morphological variants of this organism were observed by electron microscopy from one endocervical sample and one male urethral sample. We document the presence of intracellular inclusions containing only reticulate bodies, extracellular monomembrane and polymembrane phagosomes containing elementary bodies and reticulate bodies with abnormal outer membranes in the process of dividing extracellularly. These observations parallel previous in vitro studies of chlamydial persistence under adverse conditions. This capacity of C. trachomatis to undergo atypical morphological alterations in vivo may contribute to its persistence and relative resistance to antibiotics. PMID- 11763380 TI - Assessing psychological distress in patients with skin diseases: reliability, validity and factor structure of the GHQ-12. AB - OBJECTIVE: We studied reliability, validity and factor structure of the 12-item General Health Questionnaire (GHQ-12) in dermatological patients. METHOD: Subjects attending a dermatological outpatient clinic were administered the GHQ 12 and the Skindex-29. A random subsample was mailed another copy of the questionnaires to be completed within 1 week. RESULTS: A total of 2,579 subjects completed the GHQ-12. The internal consistency of the GHQ-12 was high (Cronbach's alpha = 0.88). Test-retest reliability on 137 subjects was also fairly satisfactory (intraclass correlation coefficient = 0.72), notwithstanding a re test artefact probably related to reassurance from the physician. Evidence of construct validity was provided by the pattern of correlation between scores on the GHQ-12 and on the scales of Skindex-29, which were as hypothesized. Also, GHQ 12 scores of patients in different clinical groups varied as hypothesized, with patients affected by inflammatory skin diseases scoring significantly higher than patients with isolated skin lesions. We obtained both a two-factor and a three factor solution: the latter seemed theoretically more appropriate, although the first may have practical advantages. A 'social dysfunction' factor emerged in both analyses, while the other items loaded on a 'general dysphoria' factor or on two separate factors interpreted as 'anxiety' and 'loss of self-esteem'. CONCLUSIONS: The GHQ-12 is a reliable and valid instrument with a factor structure that is quite stable across different samples as well as across diverse cultures. Its brevity and easiness of completion make it a useful tool to assess psychological distress in dermatological patients. PMID- 11763381 TI - Evaluation of sexual function in subjects taking finasteride for the treatment of androgenetic alopecia. AB - BACKGROUND: Our practical experience indicates that sexual side-effects in subjects taking finasteride 1 mg (Propecia) for androgenetic alopecia are much less common than reported in the literature. OBJECTIVE: To evaluate the sexual function in subjects taking finasteride (1 mg) compared with age-matched controls using the International Index of Erectile Function (IIEF). METHODS: The IIEF, a brief, reliable questionnaire, was self-administered to 236 patients taking Propecia and 236 age-matched males attending the Department of Dermatology of the University of Bologna. RESULTS: Statistical analysis showed no differences between scores obtained with the IIEF in subjects taking finasteride and controls. CONCLUSIONS: The sexual and erectile function of subjects taking finasteride does not significantly differ from that of age-matched controls. This is consistent with the experience of many dermatologists who do not see sexual or erectile dysfunction in patients taking Propecia. PMID- 11763383 TI - Dermatofibrosarcoma protuberans: experience with 14 cases. AB - Dermatofibrosarcoma is a rare, low-grade malignant skin tumour that can be considered the equivalent of malignant non-cutaneous soft tissue fibrohistiocytoma. The high rate of recurrence of this tumour is correlated with poor surgical management because lesions, often smaller than 2 cm in diameter, may be confused with dermatofibroma or keloid. Our findings confirm the importance of accurate diagnosis of primary lesions and the need for aggressive surgical treatment (excision of 5 cm of surrounding tissue) to lower the incidence of local relapse. PMID- 11763382 TI - Examination of mycosis fungoides for the presence of Epstein-Barr virus and human herpesvirus-6 by polymerase chain reaction. AB - BACKGROUND: The aetiology of cutaneous T-cell lymphoma (CTCL) remains unknown despite numerous investigations. In recent years, retroviruses and human herpesviruses have been implicated to play a causal part in CTCL. OBJECTIVE: The aim of this study was to elucidate the possible aetiopathogenetic role of human herpesviruses (HHV) in mycosis fungoides (MF). METHODS: Polymerase chain reaction was used to study formalin-fixed, paraffin-embedded lesional skin biopsies from 92 subjects with MF to evidence possible presence of Epstein-Barr virus (EBV) and HHV-6. RESULTS: Biopsy specimens from nine subjects (9.8%) evidenced EBV DNA, whereas all except one of the subjects (1.1%) lacked HHV-6 DNA. CONCLUSIONS: Although these findings do not support a primary aetiological role for EBV and HHV-6 in classical CTCL, the possibility remains that both viruses, particularly EBV, may act as potential cofactors in the development of CTCL. PMID- 11763384 TI - Dermatological immune restoration syndrome: does it exist? AB - Dermatological conditions are often an early clue to HIV infection and are common. As the disease progresses patients develop a dominant Th-2 immunological response that may facilitate the development of a number of skin conditions. With antiretroviral therapy the Th-1 response is restored and some skin problems regress. But, paradoxically, some cutaneous conditions may worsen, such as herpes zoster, mucocutaneous herpes, eosinophilic folliculitis and mycobacterial infections. This may be because immune restoration of a host's immunity causes recognition of silent or latent infection and results in development of the condition. PMID- 11763385 TI - Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro. AB - Langerhans cells can originate in vitro from immature precursors stimulated with granulocyte macrophage-colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha and stem cell factor (SCF). We asked whether these cytokines also control the differentiation state of Langerhans cells within the epidermis and upon leaving this tissue. We harvested sheets of human epidermis by controlled dispase hydrolysis of keratomes, cultured them in RPMI and 10% fetal calf serum for 48 h and analysed the sheets and the cells migrated spontaneously into the medium, most of which were Langerhans cells containing Birbeck granules. By flow cytometry, the intensity of CD1a expression was reduced quite evenly among Langerhans cells migrated from sheets within 48 h. The cells in the sheets underwent loss of dendrites, with a significant reduction in the cell perimeter that was prevented by GM-CSF and TNF-alpha together. Either of these cytokines induced expression of CD18 by cells in the sheets and those in the medium. Moreover, TNF-alpha induced expression of CD54 by cells in the medium, but not by those retained in the sheets, whereas human SCF induced, dose dependently, expression of CD54 by cells in the sheets, but not from those in the medium. The proliferation of allogeneic lymphocytes was much higher when stimulating Langerhans cells were harvested from cultures with any cytokine, rather than from cultures without cytokines. We conclude the following: (i) GM-CSF and TNF-alpha help to maintain full differentiation of Langerhans cells within the epidermis; (ii) cytokine influence on Langerhans cells adhesiveness is in part context dependent; and (iii) pretreatment with cytokines influences positively the number or accessory activity of Langerhans cells on lymphocytes during subsequent mixed leucocyte reaction. PMID- 11763386 TI - Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea. AB - BACKGROUND: Rosacea is a common chronic dermatosis that evolves in stages. The mite Demodex folliculorum has been implicated in its obscure aetiopathogenesis. AIM: To evaluate the importance of D. folliculorum in the aetiology and course of rosacea. METHODS: We studied 92 consecutive cases of papulopustular rosacea and 92 age- and sex-matched controls. Prevalence and density of D. folliculorum were estimated by microscopic examination of the expressed follicular content. Histological examination and immunohistochemical study of the inflammatory infiltrate were performed in 10 subjects (five with positive D. folliculorum finding and five with negative finding). RESULTS: D. folliculorum was detected in 83 (90.2%) of the 92 rosacea subjects but only 11(11.9%) of the controls. The mean mite density was 2.03 mites/visual field in the rosacea group (range 0-5, SD = 1.2) and 0.16 mites/visual field (range 0-2, SD = 0.52) in the control group. The difference was statistically significant (P < 0.0001) for both mite prevalence and density. Hair follicle infestation was associated with intense perifollicular infiltrate of predominantly (90-95%) CD4 helper/inducer T cells. We observed an increased number of macrophages and Langerhans cells only in those subjects with a positive D. folliculorum finding. CONCLUSIONS: Although Demodex mites do not seem to be the cause of rosacea, they may represent an important cofactor, especially in papulopustular rosacea. Immunohistochemical findings suggest that a delayed hypersensitivity reaction, possibly triggered by antigens of follicular origin, probably related to D. folliculorum, may occur, stimulating progression of the affection to the papulopustular stage. PMID- 11763387 TI - Wolf's isotopic response: a case of zosteriform lichen planus on the site of healed herpes zoster. AB - Based on histological findings, the patient had lichen planus. The clinical picture suggests Wolf's isotopic response on the site of healed herpes zoster. These conditions taken into account lead to the diagnosis of zosteriform lichen planus. Lichenoid papules in a dermatomal arrangement are extremely rare. The clinical, dermoscopic and histological features of this case are described. PMID- 11763388 TI - Verrucous form of chilblain lupus erythematosus. AB - A 45-year-old woman had symmetrical livid plaques with yellowish hyperkeratoses for 5 years, which progressed on to the fingers and toes and on the soles of the feet. Two years later creamy, whitish areas and maceration appeared on the buccal mucosa and the lips. A skin biopsy revealed massive collagen hyaline degeneration in the perivascular area, hyperkeratosis and hypergranulosis, small lymphocyte infiltrates with several melanophages and extravasates of erythrocytes in the upper corium in perivascular areas and hydropic degeneration of basal keratinocytes. The findings using direct immunofluorescence were compatible with lupus erythematosus (LE). Laboratory investigation showed a slight leucopenia and thrombopenia, a slightly elevated erythrocyte sedimentation rate, hypocomplementaemia C3 and C4, a high titre of rheumatoid factor and antinuclear antibodies positivity of extractable nuclear antigen. The results reflected probably the development of a systemic form of the disease. The patient was successfully managed by methylprednisolone and hydroxychloroquine. After 1 year of therapy, a new skin biopsy revealed a substantial reduction of hyperkeratosis and hyaline degeneration of collagen tissue in the perivascular areas. The combination of the extensive hyperkeratosis and hyalinization thus seems to be features of the long-lasting, untreated lesions in chilblain LE. PMID- 11763389 TI - Lichen planus pigmentosus-inversus. AB - We examined seven patients with lichen planus pigmentosus (LPP) clinically and microscopically. Clinically, all patients had a striking predominance of lesions in an intertriginous location, with most of them in the axillae. Microscopically, two biopsies were of significance. Except for the regressive lichen planus, which is usual in LPP, the active inflammatory phase was also present. In these biopsies the very intensive hydropic degeneration of basal keratinocytes was combined with the absence of compensatory increased proliferation of keratinocytes, i.e. without acanthosis. The short duration of this process probably led to the quick transformation into a long noninflammatory regressive phase with incontinence of the pigment. These specific morphogenetic dynamics are possibly why most of the morphs of LPP present as brown, non-pruritic, small inflammatory macules. Because of the highly characteristic inverse location of the lesions in our patients we propose the designation LPP-inversus for this variant of the disease. PMID- 11763390 TI - Treatment of chronic radiation ulcers with recombinant platelet-derived growth factor and a hydrophilic copolymer membrane. AB - We report on a 59-year-old woman suffering from cutaneous T-cell lymphoma of the mycosis fungoides type, who developed chronic ulcerating radiation dermatitis after total body electron beam irradiation with a cumulative dose of 36 Gy. The painful and easily bleeding ulcers could be markedly improved using a combined approach with topical platelet-derived growth factor gel and hydrophilic copolymer membranes. PMID- 11763391 TI - Pityriasis lichenoides et varioliformis acuta during pregnancy. AB - Pityriasis lichenoides et varioliformis acuta (PLEVA) is a disorder of unknown aetiology that occurs at any age and can be localized on the skin and on the mucosas. We report the case of a 24-year-old woman who presented PLEVA at her 20th week of gestation. This is, to our knowledge, the second case of PLEVA during pregnancy reported in literature. We report this case for the importance of the diagnosis of PLEVA during pregnancy because of the possible involvement of the mucosal membranes, and in particular of the vagina or cervical os of the uterus, where it may cause premature labour and/or premature rapture of the membranes. PMID- 11763392 TI - Calciphylaxis in two patients with end-stage renal disease. AB - Fatal calciphylaxis (CPX) occurred in two 71-year-old females both requiring haemodialysis for end-stage renal disease. Case 2 also had an associated follicular lymphoplasmocytoid lymphoma. Although laboratory tests disclosed normal coagulation parameters, this woman had a striking cutaneous histological picture of vessel thrombosis and finally died of disseminated intravascular coagulation. CPX is a rare but potentially life-threatening complication of renal failure. The clinical picture is primarily characterized by livedoid purpura with subsequent cutaneous ischaemia and painful ulcerations. Cutaneous ischaemic phenomena are sustained by a progressive process of vascular calcification and thrombosis involving small to medium size arteries of the dermis and subcutis. Although not yet clearly explained, the pathogenetic role of a predisposing hypercoagulability state is currently the most frequently considered hypothesis. PMID- 11763393 TI - Dapsone in rosacea fulminans. AB - Rosacea fulminans is a rare disease with female predominance characterized by abrupt onset of pustules, papules, and confluent nodules on the face. The conventional treatment consists of systemic glucocorticoids and isotretinoin. We present the case of a 56-year-old woman with a marked facial papulopustular eruption that had followed an initial period of severe seborrhoea. Conventional treatment produced no clear improvement. Dapsone treatment achieved complete healing in 5 weeks. PMID- 11763394 TI - Q-switched Alexandrite laser in the treatment of pigmented macules in Laugier Hunziker syndrome. AB - We report clearance of pigmented macules on the lips of two subjects with Laugier Hunziker syndrome using the Q-switched Alexandrite laser. Recurrence of two macules was noticed in one case 6 months after treatment and the lesions were successfully retreated. This report evaluates the efficacy and side-effect profile of the Q-switched Alexandrite laser in the treatment of lentigines in this syndrome. PMID- 11763395 TI - Hypopigmentation after non-permanent henna tattoo. AB - A young girl presented with a hypopigmentation in the shape of the sun. During a holiday in Egypt 3 months before a non-permanent henna tattoo had been applied on her right upper arm. Three to 4 days later there was a severe cutaneous reaction followed by massive swelling of the arm. The lesion took 6 weeks to subside. Patch testing revealed positive reactions to para-phenylenediamine (PPD) but not to henna or any other standard allergen. Especially in Arabic countries PPD is a common additive in natural henna preparations to enhance the weak colouring properties of the natural henna dye. We conclude that henna preparations may contain 'hidden' allergens, such as PPD, which can provoke severe cutaneous reaction without any cosensitization to the henna dye itself. PMID- 11763396 TI - Granulomatous folliculitis as a manifestation of post-herpetic isotopic response. AB - We report a case of postherpetic granulomatous folliculitis in a 52-year-old female. The several cutaneous granulomatous eruptions following herpes zoster reported in the literature include annular, sarcoid and tuberculoid granuloma, granulomatous vasculitis and granulomatous folliculitis. The mechanism of granuloma formation is probably triggered by a delayed hypersensitivity response to the virus. PMID- 11763397 TI - Histiocytic necrotizing lymphadenitis preceding systemic lupus erythematosus. AB - Necrotizing histiocytic lymphadenopathy (NHL) is a rarely observed clinical entity that is occasionally associated with systemic lupus erythematosus (SLE). The histological features of the condition have been considered to be indistinguishable from those of lymphadenitis in subjects with SLE, and the clinical symptoms of the two disorders share common features. This report presents the case history of a subject who developed SLE with central nervous system involvement 3 years following onset of Kikuchi's disease (histiocytic necrotizing lymphadenitis). Repeated lymph node biopsies confirmed the diagnosis in relation to the clinical progression. A review of the literature on this topic is also presented. PMID- 11763398 TI - Cutaneous lymphadenoma. AB - Lymphoepithelial neoplasms are biphasic tumours that contain both epithelial and lymphoid components. This heterogeneous group includes benign cutaneous lymphadenoma (CL), malignant lymphoepithelioma-like carcinoma of the skin and dermal thymus. We present two cases of CL in male subjects of 14 and 64 years of age. The latter man had a history of multiple basal cell carcinomas (BCCs) and solar keratoses. Histological sections of both tumours revealed similar features of an invasive non-ulcerated tumour with a mixed architecture of BCC and trichoepithelioma. Immunocytochemical examination revealed a biphasic epithelial tumour of follicular differentiation, possibly a variant of trichoepithelioma or a BCC. Within the epithelial islands there was a heavy infiltration that was confirmed as CD3-positive T cells and S-100-positive dendritic cells by immunocytochemistry. PMID- 11763399 TI - Rosacea fulminans triggered by high-dose vitamins B6 and B12. AB - Rosacea fulminans is a rare variant of rosacea conglobata that occurs almost exclusively in women well past adolescence. The aetiology is unknown, although immunological, hormonal, and vascular factors have been suggested. We report the case of a 17-year-old girl with rosacea fulminans that was temporally associated with daily ingestion of high-dose vitamin B supplements. The onset was sudden and cosmetically disabling. The eruption improved when the vitamin supplement was discontinued and a therapeutic regimen including isotretinoin and methylprednisolone was introduced. It seems appropriate to consider the possibility of such a vitamin B-triggered condition in cases of subjects presenting new or exacerbating facial eruptions. PMID- 11763400 TI - The anti-inflammatory activity of azulene. PMID- 11763401 TI - Mast cells in pseudo-Kaposi's sarcoma lesions. PMID- 11763402 TI - Angiolymphoid hyperplasia with eosinophilia treated by cryosurgery. PMID- 11763403 TI - Chemotherapy-induced bullous acral erythema in a subject with B-cell lymphoma. PMID- 11763404 TI - Unilateral lesions in a patient with keratosis follicularis. PMID- 11763405 TI - Mastocytoma: topical corticosteroid treatment. PMID- 11763406 TI - Ageing of the skin during menopause. PMID- 11763407 TI - Ranitidine therapy for recalcitrant warts in adults: a preliminary study. PMID- 11763408 TI - Hepatocellular damage in porcine endotoxemia: beneficial effects of selective versus non-selective nitric oxide synthase inhibition? AB - While nitric oxide (NO) is implicated as an important mediator of hypotension in sepsis and endotoxemia, its role as a mediator of tissue injury in shock is controversial. During porcine endotoxemia (lipopolysaccharide (LPS) 1.7 microg kg(-1) x h(-1) i.v. for 6 h), we compared circulatory and morphological changes in the liver induced by two different NO synthase inhibitors (N(G)-nitro-L arginine methyl ester, L-NAME, 25 mg x kg(-1) i.v. and aminoethyl-isothiourea, AE ITU, 10 mg x kg(-1) i.v.), both given after 3 h. LPS induced time-dependent tissue reactions with edema, sinusoidal dilation, packing of red cells and leukocyte infiltration, progressing to endothelial cell and hepatocyte damage, formation of thrombi, and at 6 h widespread necrosis. These changes were similar in all pigs receiving LPS, regardless of treatment with NOS inhibitors. LPS caused significant increases in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alpha glutathione S-transferase (alpha-GST), L-NAME caused further increases in AST, ALP and alpha-GST, while AE-ITU prevented the late increase in ALP and alpha-GST observed in the other LPS groups. LPS reduced liver blood flow by approximately 40%. L-NAME further reduced flow by approximately 50%, while AE-ITU restored liver blood flow to baseline values. CONCLUSION: L NAME in endotoxemia had detrimental effects on liver circulation, while AE-ITU improved liver blood flow and attenuated the late increase in liver enzymes. Liver morphology was unaffected within the 3-h observation time after NOS inhibition. PMID- 11763409 TI - Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis. AB - Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis. PMID- 11763410 TI - Early identification of bacteremia by biochemical markers of systemic inflammation. AB - Group II phospholipase A2 (PLA2-II), procalcitonin (PCT) and C-reactive protein (CRP) are useful indicators of the severity of inflammation in various infections. To compare their discriminatory abilities at an early phase of bacteremia, PLA2-II, PCT and CRP were measured upon admission and 24-48 h thereafter in 29 patients with bacteremia, non-bacteremic bacterial or viral infections. The levels of PLA2-II and PCT were higher in bacteremia than in non bacteremic bacterial or viral infections. PCT was highest upon admission, PLA2-II peaked at 12-24h, whereas CRP peaked one day later. At < or =24h, the AUC(ROC)s of PLA2-II and PCT were superior to those of CRP. Thereafter, the AUC(ROC)s of PLA2-II and PCT decreased and those of CRP increased. PLA2-II at cut-off level of 150 microg/L and PCT at 2-6 microg/L showed high sensitivity and specificity for bacteremia within the first 24h. In conclusion, PLA2-II and PCT are useful markers for early diagnosis of bacteremia. Devising analytical methods suitable for point-of-care testing would further enhance the clinical utility of the measurement of serum PLA2-II and PCT. PMID- 11763411 TI - Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes. AB - Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes in neuroendocrine responses occur early in the course of diabetes, we investigated the responses to insulin induced hxypoglycaemia during the first year of type 1 diabetes. Autonomic and somatic nerve function tests were performed concomitantly. Six type 1 diabetes patients were studied 3 and 12 months after diagnosis of diabetes. Hypoglycaemia was induced by i.v. insulin infusion after an overnight normalization of blood glucose. Autonomic nerve function was evaluated by cardiovascular tests, and somatic nerve function by nerve conduction velocities A 50% reduction was found in adrenaline (p < 0.025) and noradrenaline (p < 0.05) responses to hypoglycaemia; PP, too, was significantly diminished at 12 months compared with 3 months after diagnosis of type 1 diabetes. Rate of glucose recovery did not differ at month 12 compared with month 3. Cardiovascular autonomic nerve function tests did not change and remained within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i.e. a higher threshold (i.e. a lower blood glucose level) for hypothalamic activation of the sympathoadrenal system. PMID- 11763412 TI - Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation. AB - BACKGROUND: Treatment with hyperbaric oxygen (HBO2) is controversial when treating disorders other than decompression sickness. Still, HBO2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO2 treatment on cultured endothelial cells in a simulated ischaemia-reperfusion model. METHODS: To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t PA), urokinase plasminogen activator (uPA) and the antagonist. plasminogen activator inhibitor type one (PAI-1). RESULTS: Immediately after 8 h of total anoxia and reoxygenation with HBO2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. CONCLUSION: In this ischaemia-reperfusion model. HBO2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion. PMID- 11763413 TI - Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS. AB - A new method for the determination of N,N-dimethyl-5-hydroxytryptamine (bufotenine), N,N-dimethyltryptamine (DMT)*, 5-methoxy-N,N-dimethyltryptamine (5 MeODMT), and N-methyltryptamine (NMT) was developed using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Identification of the analytes is based on liquid chromatographic retention times of analytes and two fragment ions produced by a triple quadrupole mass spectrometer. Quantification is based on electrospray ionization (ESI), and multiple reaction monitoring (MRM) was also utilized for getting better selectivity. The analytes and internal standard were separated from the urine matrix by solid-phase extraction (SPE). The method was applied for the determination of these compounds in urine samples of patients from surgical, medical and psychiatric wards. Of the dimethylated amines, only bufotenine was found in significant amounts (up to 34 microg/L). In keeping with our earlier results, the bufotenine excretion of psychiatric patients was found to be higher than that of the somatic patients. Method, procedure, considerations, statistical evaluations and urine sample spectra are presented. PMID- 11763414 TI - Hypothalamic-pituitary-adrenal response to different tests in type 1 diabetes mellitus. AB - OBJECTIVE: To determine whether different tests of the adrenocorticotropic hormone (ACTH) reserve are influenced by diabetic state and metabolic control in newly diagnosed type 1 diabetic patients. DESIGN AND METHODS: We evaluated the ACTH reserve in 10 patients with uncomplicated type 1 diabetes during periods of poor and improved metabolic control and in 10 healthy subjects. The ACTH-cortisol secretion was assessed by a diurnal profile, an intravenous corticotropin releasing hormone (CRH) test and an insulin tolerance test (ITT). RESULTS: The diurnal profiles were similar in all groups. CRH resulted in a diminished ACTH response during poor compared with improved metabolic control (mean+/-SD) (AUC 4950+/-4227 vs. 5847+/-3788 ng/L min, p<0.05). The response in the diabetic patients during improved metabolic control was of the same magnitude as in the control subjects (5934+/-1778 ng/L x min). ITT elicited a similar ACTH and cortisol response in the diabetic patients during poor and improved metabolic control as in the healthy control subjects. CONCLUSIONS: The ITT was uninfluenced by diabetic state and metabolic control and should therefore be considered the method of choice in evaluation of the ACTH reserve in patients with type 1 diabetes. PMID- 11763415 TI - Levels of three inflammation markers, C-reactive protein, serum amyloid A protein and procalcitonin, in the serum and cerebrospinal fluid of patients with meningitis. AB - The levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) in blood are increased in patients with inflammatory diseases as acute phase proteins. Most of the presently used indicators of inflammation, such as body temperature, white cell count, erythrocyte sedimentation rate or CRP, are non-specific parameters. In contrast, procalcitonin (PCT) has been reported to be selectively induced by severe bacterial infection during the systemic inflammatory response syndrome (SIRS), and also in sepsis or multiorgan dysfunction syndrome. PCT expression is only slightly induced, if at all, by viral infections, autoimmune disorders, neoplastic diseases and trauma of surgical intervention. We measured the concentrations of CRP, SAA and PCT in the sera and cerebrospinal fluid (CSF) of 30 patients with bacterial, viral, or mycotic meningitis, and 12 patients with a noninflammatory central nervous system disease as controls. An extremely high CRP level in CSF of above 100 microg/L was seen in all seven bacterial meningitis patients and in only 10% of the viral meningitis patients. A high SAA level in CSF of greater than 10 microg/L was observed in all of the bacterial meningitis and mycotic meningitis patients, and in 95% of the viral meningitis patients. Among those with bacterial meningitis, the serum PCT level was more elevated in those with more serious bacterial meningitis. The PCT level in the CSF did not significantly differ among the patients with the three types of meningitis. However, the serum PCT level was very high above 0.1 microg/L in all seven bacterial meningitis patients, especially in the clinically serious cases. PMID- 11763416 TI - Serum cystatin C is a better marker for preeclampsia than serum creatinine or serum urate. AB - Altered renal function is an essential component of the pathophysiological process in preeclampsia. The kidneys play a significant part in the turnover of most low molecular weight substances such as creatinine, urate and cystatin C. The present work was undertaken to investigate if the serum levels of these components are altered in characteristic ways in preeclampsia, and can be used to assist in the diagnosis of this condition. The serum levels were therefore determined in samples from 100 healthy women at term as well as in 45 samples of patients with preeclampsia (diastolic blood pressure >90 mmHg; urinary albumin excretion >300 mgL(-1)). The levels of all three components were significantly higher in samples from preeclamptic patients with the mean+SD being 1.55+/-0.29 vs. 1.05+/-0.19 mg L(-1) for cystatin C, 70+/-23 vs. 56+/-9.7 micromol L(-1) for creatinine, and 413+/-128 vs. 305+/-61 micromol L(-1) for urate. Receiver operating characteristic analysis demonstrated that the serum level of cystatin C had a superior diagnostic accuracy for preeclampsia compared to those of serum urate and creatinine and that the diagnostic accuracy of serum urate was better than that of serum creatinine. PMID- 11763417 TI - Invasiveness in vitro and biological markers in human primary glioblastomas. AB - Invasion of spheroids from 20 human primary glioblastomas into precultured fetal rat brain tissue in culture has been studied and quantified. Between 30 and 98 percent of the normal brain tissue was destroyed by invading glioma cells within 4 days. The degree of invasion did not correlate with patient survival. A slightly higher invasiveness and shorter survival was seen in tumors with EGF receptor overexpression, and the opposite pattern was found for tumors with a TP53 mutation. The degree of invasiveness in vitro was far higher than would be expected from the dynamics of clinically observed tumor spread. This suggests that mechanisms suppressing invasion may be operative in the normal brain; alternatively the differences may be due to a higher permissiveness of the fetal brain tissue for invasion in vitro. PMID- 11763419 TI - Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. AB - Estramustine phosphate (EMP) is an anti-microtubule agent that induces apoptosis of glioma cells. We investigated whether EMP caused apoptosis through the alkylating effect of its nitrogen mustard component or by phosphorylation of bcl 2 like other anti-microtubule agents in normal human astrocyte and human malignant glioma cell lines. Apoptosis was seen in glioma cells treated either with nitrogen mustard or EMP and expression of bcl-2 mRNA was not changed by exposure to the drug. An immunoprecipitation study only found phosphorylation bcl 2 in glioma cells exposed to EMP and not in cells exposed to nitrogen mustard. These results indicate that induction of apoptosis in glioma cells by EMP is mediated by phosphorylation of bcl-2. PMID- 11763418 TI - Antiproliferative and apoptotic effect of ascorbyl stearate in human glioblastoma multiforme cells: modulation of insulin-like growth factor-I receptor (IGF-IR) expression. AB - Human glioblastomas (gliomas) are characterized as highly invasive and rapidly growing brain tumors. In this study, we present data on in vitro effect of ascorbyl stearate (Asc-S), a liphophilic derivative of ascorbic acid on cell proliferation, transformation, apoptosis and modulation of expression of insulin like growth factor-I receptor (IGF-IR) in human glioblastoma multiforme (T98G) cells. Asc-S showed significant inhibition of fetal bovine serum and human recombinant insulin-like growth factor-I (IGF-I) dependent cell proliferation in a dose dependent manner. Treatment of T98G cells with 0, 50, 100 and 150 microM Asc-S for 24h slowed down the cell multiplication cycle with significant accumulation of cells at late S/G2-M phase of cycle. Asc-S treatment (100 microM) reversed the transformed phenotype as determined by clonogenecity in soft agar and also induced apoptosis of T98G. These changes were found to be associated with significant decrease in IGF-IR expression in dose and time dependent manner compared to untreated controls. The data clearly demonstrate that Asc-S has antiproliferative and apoptotic effect on T98G cells probably through modulation of IGF-IR expression and consequent facilitation of programmed cell death. PMID- 11763420 TI - Phase II study of thalidomide in the treatment of recurrent glioblastoma multiforme. AB - Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatment of recurrent glioblastoma multiforme. Patients were treated with 100 mg/day of Thalidomide, increased at weekly intervals by 100 mg to a maximum tolerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for response and 39 for toxicity. Two patients (5%) achieved a partial response and 16 (42%) had stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or performance status. Overall Thalidomide was well tolerated with no grade 4 toxicities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients developed tachyphylaxis. There was no correlation demonstrated with plasma vascular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined once we have established reliable surrogate endpoints. PMID- 11763421 TI - Efficacy of intratumoral delivery of mitoxantrone in recurrent malignant glial tumours. AB - Ninety-nine patients bearing recurrent malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study. All patients were previously managed with radiotherapy 60 Gy total dose and chemotherapy with nitrosoureas and platinum compounds. At recurrence they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally by delivering 4mg of mitoxantrone every 20 days through the Ommaya reservoire, and 25 GBL (group C) treated with a second surgery and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoir after repeat surgery. A trend to different demographic features among subgroups (with locoregionally treated patients and patients undergoing repeat surgery being younger than the others) was seen in this non-randomized study, but this was not statistically significant. Median overall survival was 27, 26 and 15.5 months respectively for groups c, b and a (log-rank = 0.1). After tumor recurrence median survival was 16.8, 12 and 6.6 months respectively for groups c, b and a (log-rank = 0.001) For the 29 AA, overall survival was 48.5 and 100 months (log-rank = 0.03) if treated locally with second tumor debulking. Our results stress the opinion that a second operation could be indicated only if it is a part of a therapeutic protocol to allow a locoregional treatment. Moreover we can finally assume that local delivery of chemotherapy after tumor recurrence, possibly extends patients survival but certainly improves the number of long survivors. PMID- 11763422 TI - Paraganglioma of the pituitary fossa: diagnosis and management. AB - Paraganglioma of the sellar area is extremely rare with only six cases having been reported in the literature. Surgical removal of these tumors is difficult, and the transsphenoidal approach usually results in limited resection. Most authors who published reports on this tumor recommended radiation therapy after partial removal of the tumor. However, considering the benign nature of these tumors, the risk of radiation-induced endocrine insufficiency and optic neuropathy and the lack of proven effectiveness of radiotherapy, its value remains controversial. We describe a 48-year-old woman with parasellar paraganglioma who presented with headaches, visual loss and oligomenorrhea. Magnetic resonance imaging (MRI) showed an invasive tumor in the sellar and parasellar areas which extended to both cavernous sinuses and compressed the optic chiasm and the left internal carotid artery. Surgery by the transsphenoidal approach enabled only limited biopsy of the tumor. The patient was reoperated by an extended pterional approach which resulted in a subtotal removal of the tumor and adequate decompression of the adjacent structures. She received no adjuvant treatment during the 8-year postsurgical follow-up and remained in good health. A repeated MRI showed no change in the size of the residual tumor. Contrary to the therapeutic recommendations described in previous reports, we favor postoperative adjuvant therapy only if the symptoms or signs of cranial nerve compression persist following maximal tumor removal, or if there is evidence of subsequent growth of residual tumor. PMID- 11763423 TI - Extraneural metastasis in a child with atypical teratoid rhabdoid tumor of the central nervous system. AB - Atypical teratoid rhabdoid tumor is a distinctive brain tumor appearing in infancy and early childhood. Leptomeningeal dissemination is common, both at presentation and relapse. Extracranial metastases of the central nervous system tumors are rarely seen. To our knowledge there is only one report with an atypical teratoid rhabdoid tumor metastasizing via a ventriculoperitoneal shunt. We describe the first case of atypical teratoid rhabdoid tumor of the central nervous system who developed lung metastasis without the presence of a shunt. PMID- 11763424 TI - Solitary fibrous tumours of the meninges: case series and literature review. AB - We report four new cases of meningeal Solitary Fibrous Tumour (SFT). Two patients presented with raised intracranial pressure from posterior fossa SFT, and the third developed hemiparesis and dysphasia due to a large lesion that originated in the left middle cranial fossa. These were successfully excised and the patients remain well at follow-up of between 1 and 3 years. The fourth patient, a 71-year-old man, suffered an intracerebral haemorrhage and later died from a malignant SFT that had invaded the falx cerebri, superior sagittal sinus, and brain. This is the first description of a locally aggressive meningeal SFT with multiple atypical histological features. The 31 previously reported cases of meningeal SFT are reviewed. They occur at all ages and may be relatively more common in the posterior fossa and spine. Intracranial SFT originate from the dura and are probably indistinguishable from meningiomas on imaging and at surgery. In contrast, approximately two-thirds of spinal SFT have no dural attachment. Histologically, SFT are spindle-cell neoplasms with a characteristic immunohistochemical profile of CD34, vimentin, and bcl-2 positivity. Data on outcome for patients with meningeal SFT are limited. At other sites, however, extent of resection is the most important prognostic factor, and invasion or metastasis can occur with histologically benign SFT. Meningeal SFT should, therefore, be excised as completely as possible and followed carefully in the long-term. PMID- 11763425 TI - Pseudotumoral demyelination: a diagnosis pitfall (report of three cases). AB - Rare forms of demyelinating disease such as Balo's concentric sclerosis or Schilder's disease may simulate brain tumors, both clinically and on the computed tomography (CT) and magnetic resonance imaging (MRI). Even the histopathological diagnosis after a biopsy is not entirely reliable. We report three cases of pseudotumoral demyelinating disorders having required a stereotaxic biopsy, one of which was erroneously diagnosed as a malignant astrocytoma. We describe MRI especially the intense contrast enhancement with ill-defined margins, and the mild mass effect. We then detail the histopathological processes upon which differential diagnosis with a tumor can be based. PMID- 11763427 TI - CDKN2A/p16 in ependymomas. AB - Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas. PMID- 11763426 TI - A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma. AB - Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses > or = 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score > or = 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score > or = 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas. PMID- 11763428 TI - Acidic vesicles of Schistosoma mansoni. AB - The fluorescent probe LysoTracker Red was used to examine for the presence of acidic vesicles in cercariae and schistosomula of Schistosoma mansoni. Acidic vesicles were widely distributed throughout the body of freshly transformed schistosomula and 24-h-old schistosomula but were absent from cercariae. The vesicles of freshly transformed schistosomula were undetectable after incubation with drugs that affect the functionality of acidic vesicles including monensin, ouabain, primaquine, and amiloride. In 24-h transformed schistosomula, the same effect was observed with monensin but not with ouabain, primaquine or amiloride. Praziquantel also affected the acidic vesicles of the schistosomula. We suggest that these acidic vesicles could be large lysosome-like organelles. PMID- 11763429 TI - The analysis of Plasmodium vivax Duffy receptor binding domain gene sequence from resurgent Korea isolates. AB - The Duffy binding domain gene structures of Plasmodium vivax facilitate the invasion of erythrocytes. Human erythrocytes that lack Duffy blood group antigens are resistant to invasion by P. vivax. We have sequenced the Duffy binding domain gene from eight P. vivax isolates collected from malaria cases in South Korea. When compared to isolates from other regions in the world, the amino acid sequences of the Korean isolates showed unique variations in region II. From 606 sequenced amino acids, 32 variations were found. Of these, three variations were regularly found in positions 424, 437 and 503 of the Sal-1 amino acid sequence. In region III, six isolates had a loss of the 30 bp (FAESTKSAE) insert. However, six isolates had 6 bp (SD) inserts at the end of region III. Two cases had a reverse pattern. Our results suggest that the P. vivax currently found in South Korea are unique when compared to other isolates and can be divided, by the analysis of their molecular structure, into two strains. PMID- 11763430 TI - Use of a novel DNA melting profile assay for the identification of PCR-amplified genomic sequences encoding for variant-specific surface proteins from the clonal GS/M-83-H7 line of Giardia lamblia. AB - During infections, Giardia lamblia undergoes a continuous change of its major surface antigens, the variant-specific surface proteins (VSPs). Many studies on antigenic variation have been performed using G. lamblia clone GS/M-83-H7, which expresses surface antigen VSP H7. The present study was focused on the identification and characterization of vsp gene sequences within the genome of the clonal G. lamblia GS/M-83-H7 line. For this purpose, we applied a PCR which specifically amplified truncated sequences from the 3'-terminal region of the vsp genes. Upon cloning, most of the vsp gene amplification products were shown to be approximately identical in size and thus could not be distinguished from each other by conventional gel electrophoresis. In order to pre-estimate the sequence complexity within the large panel of vsp clones isolated, we elaborated a novel concept which facilitated our large-scale genetic screening approach: PCR products from cloned DNA molecules were generated and then subjected to a DNA melting profile assay based on the use of the LightCycler Instrument. This high throughput assay system proved to be well suited to monitor sequence differences between the amplification products from closely related vsp genes and thus could be used for the primary, sequence-related discrimination of the corresponding clones. After testing 50 candidates, vsp clones could be divided into five groups, each characterized by an individual DNA melting profile of the corresponding amplification products. Sequence analysis of some of these 50 candidates confirmed data from the aforementioned assay in that clones were demonstrated to be identical within, but different between, the distinct groups. The nucleotide and deduced amino acid sequences of five representative vsp clones showed high similarities both among each other and also with the corresponding gene segment of the variant-specific surface antigen (VSP H7) expressed by the original GS/M-83-H7 variant type. Furthermore, three of the genomic vsp sequences turned out to be identical to vsp sequences that represented previously characterized transcription products from in vivo- or in vitro-switched GS/M-83 H7 trophozoites. In conclusion, the DNA melting profile assay seems to be a versatile tool for the PCR-based genotyping of moderately or highly diversified sequence orthologues. PMID- 11763431 TI - More efficient allopatric combinations of Fasciola hepatica and Lymnaea truncatula due to modification of redial development? AB - Experimental infections of two susceptible French populations of Lymnaea truncatula (Courcelles and Saint Ours) with an allopatric (Fes, Morocco) or a semi-sympatric (Limoges, France) isolate of Fasciola hepatica miracidia were performed to determine the effect of allopatric miracidia on redial and cercarial production. In both populations, cercarial release was significantly greater in allopatric than in semi-sympatric snails. Compared to semi-sympatric snails, the examination of allopatric snails killed from day 14 to day 35 post-exposure demonstrated (1) a significant decrease after day 28 in the number of daughter rediae (R2a group) exiting from the first-appearing mother redia (R1a redia), and (2) the differentiation of numerous daughter rediae (R2b group) in the body of second-appearing mother rediae (R1b group). These experiments demonstrated that the exposure of L. truncatula to an allopatric isolate of miracidia disturbed the usual developmental pattern of redial generations and caused the formation of numerous R2b rediae. The authors hypothesized that the increase in cercarial release noted in allopatric snails would be assured by the rediae from the R2b group after their emergence from the body of R1b mother rediae. PMID- 11763432 TI - Change in Plasmodium falciparum genotype during successive malaria episodes in Gabonese children. AB - Extensive polymorphism in the malaria parasite Plasmodium falciparum is one of the major obstacles to controlling the disease. With the aim of analysing the dynamics of P. falciparum inoculations, we investigated the parasite genotypes of successive malaria episodes. Polymerase chain reaction was performed on blood samples collected longitudinally from 31 children in Lambarene, Gabon. The polymorphic regions of the merozoite surface antigens 1 and 2 were used as genetic markers. The data show that children in this area are exposed to many different P. falciparum strains. In a few cases, the same parasite genotypic pattern was observed in samples from two consecutive clinical attacks indicating probable recrudescences after therapy. In six cases the first successive infections with a particular merozoite surface antigen (MSA)-2 strain (3D7) were followed by infections with the other MSA-2 genotype (FC27). In all other cases the genetic characteristics of the parasite were different from one infection to the next, indicating that reinfection was caused by a new parasite strain. PMID- 11763433 TI - Hyperkeratotic mange caused by Sarcoptes scabiei (Acariformes: Sarcoptidae) in juvenile human-habituated mountain gorillas (Gorilla gorilla beringei). AB - To facilitate ecotourism and behavioral research, free-ranging mountain gorillas (Gorilla gorilla beringei) have been habituated to humans. During routine health monitoring, five juvenile gorillas were observed with active crusted dermatitis and alopecia. Papular and vesicular lesions and crusts with papular eruption and oozing were numerous and disseminated over the body of one gorilla with a confirmed infestation of scabies. In this gorilla, the hyperkeratotic crusts were loose and thick with a flaky and scaly appearance. Histologically, the epidermis was thickened, displayed hyperkeratosis and was infiltrated with lymphocytes and neutrophils. Examination of skin scraping yielded a positive identification of adults and eggs of Sarcoptes scabiei mites. The gorillas were treated with ivermectin, 200 mg kg(-1). As S. scabiei mites can cross-infect various mammalian species causing self-limiting dermatitis, these ectoparasites can be propagated in the habitats shared by gorillas, people, and livestock, and therefore they represent an anthropozoonotic threat. PMID- 11763434 TI - Blastocystis hominis modulates immune responses and cytokine release in colonic epithelial cells. AB - An experimental in vitro model has been developed in order to determine whether Blastocystis hominis is able to trigger inflammatory cytokine response in colonic epithelial cells. After 24 h incubation of B. hominis with the cell lines HT-29 and T-84, B. hominis cells were not able to cause cytopathic effects, but significant increases in the release of the cytokines IL-8 and GM-CSF could be observed. However, after the first 6 h of co-incubation, the production of IL-8 was not increased in HT-29 cells, and even reduced when Escherichia coli (bacteria or lipopolysaccharide) was present during co-incubation. Similar effects were observed using supernatants of B. hominis culture. These data indicate that B. hominis induces as well as modulates the immune response in intestinal epithelial cells, and we conclude that different pathophysiological events may occur during B. hominis infection. PMID- 11763435 TI - PCR-ELISA: a new simplified tool for tracing the source of cryptosporidiosis in HIV-positive patients. AB - Cryptosporidium parvum is a major parasitic cause of death in end-stage AIDS patients that results from both zoonotic and person-to-person transmission. Recent studies have provided evidence that parasites causing zoonotic disease and those causing anthroponotic infection are genetically distinct. Isolates carrying "animal"-type genetic markers were presumed to be the result of zoonotic spread, either directly or through contaminated food and water. The need for a genotype specific diagnostic tool that can provide clues as to the origin and possible modes of spread of C. parvum strains has been recognised. Here, we report the development of such a tool for C. parvum based on polymerase chain reaction enzyme linked immunosorbent assay that enables the accurate typing of isolates from HIV-seropositive and HIV-negative patients presenting with diarrhoea from the United Kingdom and Canada. This study also showed that zoonotic transmission might be predominant in the HIV-positive patient group in the United Kingdom. PMID- 11763436 TI - Fine structure, freeze-fracture and deep-etch views of the sheath and cuticle of microfilariae of Litomosoides chagasfilhoi (Nematoda: Filarioidea). AB - The fine structure of the sheath and the cuticle of microfilariae of the filariid Litomosoides chagasfilhoi is described based on observations made using transmission electron microscopy (TEM) and especially on deep-etched replicas of fully developed intrauterine microfilariae and mature stretched microfilariae released by adult females through cultivation in vitro. TEM showed that the sheath was trilaminated. In contrast, in deep-etching replicas the sheath presented two layers: an inner layer composed of tightly arranged globular material, and an outer layer whose external surface was relatively smooth. Both in thin sections and in classical freeze-fracture and deep-etched replicas, the cuticle presented two distinct regions: an external one, corresponding to the trilaminated epicuticle, and an inner one, corresponding to the inner cuticle. Deep-etching replicas revealed that the epicuticle presented several structures on the annulations of the microfilariae and that the inner region was composed by two parallel rows of globular structures. PMID- 11763437 TI - A monoclonal antibody to Trypanosoma cruzi trypomastigotes recognizes a myosin tail epitope. AB - A monoclonal antibody, 1E7, raised against tissue culture-derived trypomastigotes of Trypanosoma cruzi reacted with proteins located at the perinuclear region of the parasite as detected by immunofluorescence and immunogold electron microscopy. The antibody also recognized antigens in all trypanosomatids tested, including T. cruzi epimastigotes, as well as in many mammalian cells. Five principal antigens of 140-270 kDa soluble in 1 M NaCl were recognized by the monoclonal antibody, suggesting that the epitope may belong to more than one polypeptide since the same bands appeared even when the samples were treated with high concentrations of denaturing agents. The antibody reacted in Western blots with muscle myosin. Bacterial clones expressing fast skeletal muscle myosin head or tail cDNAs upon IPTG induction were used to demonstrate that 1E7 monoclonal antibody recognizes an epitope present in the tail region of the myosin heavy chain. This result adds to the on-going discussion related to the possible existence of an auto-immune component in the immunopathogenesis of Chagas' disease due to cross-reactive epitopes shared by the parasite and cardiac myosin. PMID- 11763438 TI - Immunocytochemical localization of antigens recognized by asymptomatic microfilaremic patient's antisera in microfilariae of Wuchereria bancrofti. AB - Ultrathin sections of microfilariae of Wuchereria bancrofti embedded in hydrophilic resin were incubated with sera from patients, using antisera from asymptomatic microfilaremic patients with different microfilarial densities [1 100 microfilariae (mf)/ml, 101-500 mf/ml, > 1,000 mf/ml]. All groups studied showed reactivity against relevant epitopes in all tissues of microfilariae of W. bancrofti, instead of being localized in a specific nematode region, although the number of colloidal per square micron was inversely proportional to the microfilaremia. Such results confirm data obtained by other authors and indicate a possible role for the humoral response in the mechanism for the destruction of circulating microfilariae. PMID- 11763439 TI - Attempt to differentiate Leishmania (Leishmania) amazonensis, L. (L.) chagasi, Leishmania (Viannia) braziliensis and L. (V.) guyanensis using the SSR-PCR technique. AB - The ability to differentiate reference strains of Leishmania (Leishmania) amazonensis, L. (L.) chagasi, Leishmania (Viannia) braziliensis and L. (V.) guyanensis was evaluated using the simple sequence repeat polymerase chain reaction (SSR-PCR) technique. This technique differentiates the Leishmania species, generating distinct DNA amplicon profiles. The SSR-PCR profiles were similar to but more reproducible than those produced by RAPD. SSR-PCR is presented as an alternative to other molecular methods for the differentiation of Leishmania species or strains. PMID- 11763440 TI - Milestones of protozoan research at Bayer. PMID- 11763441 TI - Isolation, characterisation and organisation of histone H1 genes in African trypanosomes. AB - A tandemly arranged gene family coding for histone H1 in African trypanosomes is described. Many variants, differing by some substitutions and/or deletions in their monotone and repetitive amino acid sequences, are found. The different variants can be sorted into three subtypes using their N-terminal region. PCR amplification experiments with primers specific to these three H1 subtypes suggest that the genes may be separated into two transcriptional units. Heterogeneity among species, subspecies and even strains was found. The transcripts are polyadenylated and the trans-splicing site is located very closely to the start codon. The intergenic regions are typical when compared to other polycistronic clusters described in trypanosomes. Amino acid sequence motifs may explain differences seen in chromatin compaction patterns between African and American trypanosomes. PMID- 11763442 TI - Trypanosoma cruzi: the development of estrus cycle and parasitemia in female mice maintained with or without male pheromones. AB - Female BALB/c or C57B1/6 mice, kept in small groups of three or five animals with or without male odor, all had a similar progesterone and corticosterone level, mean number of estrus and duration of estrus cycle. However, if males were kept in the same room, the mean duration of the estrus cycle was longer for both strains; and C57B1/6 females had a significantly higher number of estrus than BALB/c mice and showed a tendency to synchronize the estrus cycle within a group. After infection of females of both mouse strains with vector-derived metacyclic trypomastigotes of Trypanosoma cruzi, anestrus with intense phlegm production occurred during the acute phase of infection and this was positively correlated with higher parasitemia. Within individual groups of BALB/c mice, the female with the relatively highest corticosterone and progesterone level had the lowest parasitemia. In groups kept separate from male pheromones, one or two females in each group developed high parasitemias. PMID- 11763443 TI - Experimental Chagas disease: the influence of sex and psychoneuroimmunological factors. AB - The effects of gender and psychoneuroimmunological factors resulting from the social environment and status of males were investigated with regard to the concentrations of testosterone and corticosterone and the course of Trypanosoma cruzi infection in mice. Hormone concentrations varied considerably; and only testosterone concentrations showed a tendency to be higher in dominant males. Females kept singly developed lower and more similar parasitaemias than males kept singly or together with a female. This difference was significant when comparing groups of females or males. Within groups of male mice, parasitaemia was strongly correlated with the social position, being high in inferior males and low in dominant ones. The importance of these findings is that they clearly prove that chronic social stress in males strongly affects the course of infection with T. cruzi. PMID- 11763444 TI - Artificial urushi. AB - A new concept for the design and laccase-catalyzed preparation of "artificial urushi" from new urushiol analogues is described. The curing proceeded under mild reaction conditions to produce the very hard cross-linked film (artificial urushi) with a high gloss surface. A new cross-linkable polyphenol was synthesized by oxidative polymerization of cardanol, a phenol derivative from cashew-nut-shell liquid, by enzyme-related catalysts. The polyphenol was readily cured to produce the film (also artificial urushi) showing excellent dynamic viscoelasticity. PMID- 11763445 TI - Acid-base centers and acid-base scales in ionic solids. AB - For the case of ionic crystals it is shown to be most straightforward and consistent to define acidity/basicity by the (electro-)chemical potential of the respective ion, in a similar fashion to the way that the Fermi level (i.e.. electrochemical potential of the electron) characterizes the redox state. The isomorphy is explicitly expressed by using the energy-level diagrams introduced for electrons in semiconductor physics. Without having to make further assumptions it is possible 1) to compare acidity/basicity between different solids, 2) to link internal and surface acidity/basicity, and 3) to establish acidity/basicity scales for ionic solids. The point defects are revealed to be the natural acidic and basic elementary centers, and associates between them to be the internal acids/bases exchanging these elementary centers. Even though acidity/basicity is an overall property of the solid, the number of point defects (if dilute) directly represents these properties in the same way as H+ or OH- accomplish this for aqueous solutions. PMID- 11763446 TI - The total synthesis of C-glycosides with completely resolved seven-carbon backbone polyol stereochemistry: stereochemical correlations and access to L configured and other rare carbohydrates. AB - The de novo synthesis of a full set of hydroxymethyl C-glycosides from only two precursors is described. The seven-carbon target molecules contain five stereocentres and bridge the stereochemical gap between natural D-configured and non-natural L-configured series of hexoses. Key steps include hydroxylation, differential protection, stereoselective reduction and desymmetrization of 8 oxabicyclo[3.2.1]oct-6-enes. C-Terminus differentiation and C-terminus excision of the seven-carbon polyol backbone lead to hexoses, including those of the L series. A stereochemical and genetic classification of C-glycosides is presented. PMID- 11763447 TI - Regioselective synthesis of a branched isomer of nonylphenol, 4-(3',6'-dimethyl 3'-heptyl)phenol, and determination of its important environmental properties. AB - A method for the synthesis of a pure nonylphenol isomer, 4-(3',6'-dimethyl-3 heptyl)phenol, by Friedel-Crafts reaction between anisole and 3-bromo-3,6 dimethylheptane that gives a 47.3% overall yield is reported. The reactions were followed by GC-MS, and the chemical structures are in agreement with the NMR and IR spectra. The log K(ow) value for this compound, its water solubility, vapor pressure, and Henry's Law constant were also determined. These physicochemical properties were required for prediction of the compound's behavior in aquatic ecosystems. PMID- 11763448 TI - Metal complexation with Langmuir monolayers of histidyl peptide lipids. AB - Langmuir monolayers made from peptide-lipid molecules represent a novel direction in the research areas of biomimetic interfaces and two-dimensional supramolecular chemistry. Peptide structures and molecular recognition activities toward other guest molecules have been the focus of previous study. This study reports the investigation of metal complexation to histidine-containing peptide lipids in the organized Langmuir, Langmuir-Schaefer, or Langmuir-Blodgett films. Three peptide lipids PEP1-PEP3, with a histidine amino acid incorporated in the middle of the peptide, were designed and synthesized. The monolayer structures and metal binding activities of each peptide lipid and their 1:1:1 molar ratio mixture were studied by thermodynamic and spectroscopic techniques. It was found that hard Lewis acid type metal cations such as K+ and Mg2+, and borderline or soft metal cations such as Zn2+, Cu2+, and Cd2+ exhibit clearly different binding activity toward peptide-lipid monolayers. The conformational changes of peptides upon binding with Cu2+ and Zn2+ were partially revealed by FT-IR spectroscopic studies. Furthermore, by adding a fluorescent-probe lipid to the peptide monolayer, dramatic fluorescence change was observed when Cu2+ or Zn2+ bound to the Langmuir and Langmuir-Schaefer films of peptide-lipid monolayers. Metal protein complexation plays a crucial role in the function and activity of proteins and enzymes. Investigation of metal complexation to organized peptide Langmuir monolayers may provide an alternative approach for the development of artificial metalloproteins and novel supramolecular systems or materials. PMID- 11763449 TI - Crucial influence of solvent and chirality-the formation of helices and three dimensional nets by hydrogen-bonded biimidazolate complexes. AB - Deprotonation and recrystallisation of racemic [Co(2,2'-biimidazole)3][NO3]3 by ammonia in water/dimethylformamide solutions gave crystals of [Co(Hbiim)3] x 0.8H2O x 0.5DMF (2: Hbiim = monoanion of 2,2'-biimidazole, DMF = dimethylformamide), a porous material that contains fourfold interpenetrating (10.3) three-dimensional nets formed by neutral, hydrogen-bonded [Co(Hbiim)3] units, with DMF molecules in the narrow channels. Recrystallisation of [delta Co(2,2'-biimidazolate)3] gave helices instead of the expected (10,3)-a net. These results are discussed in the light of additional density functional theory and molecular mechanics calculations and the X-ray structure of [Co(H2biim)3][NO3]3. PMID- 11763450 TI - Indenylidene complexes of ruthenium: optimized synthesis, structure elucidation, and performance as catalysts for olefin metathesis--application to the synthesis of the ADE-ring system of nakadomarin A. AB - An optimized and large scale adaptable synthesis of the ruthenium phenylindenylidene complex 3 is described which employs commercially available diphenyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual structure of the complex have been ruled out by a full analysis of its NMR spectra. A series of applications to ring closing metathesis (RCM) reactions shows that complex 3 is as good as or even superior to the classical Grubbs carbene 1 in terms of yield, reaction rate, and tolerance towards polar functional groups. Complex 3 turns out to be the catalyst of choice for the synthesis of the enantiopure core segment 77 of the marine alkaloid nakadomarin A 60 comprising the ADE rings of this target. Together with a series of other examples, this particular application illustrates that catalyst 3 is particularly well suited for the cyclization of medium-sized rings by RCM. Other key steps en route to nakadomarin A are a highly selective intramolecular Michael addition setting the quaternary center at the juncture of the A and D rings and a Takai-Nozaki olefination of aldehyde 73 with CH2I2, Ti(OiPr)4 and activated zinc dust. PMID- 11763451 TI - Synthesis of conformationally locked L-iduronic acid derivatives: direct evidence for a critical role of the skew-boat 2S0 conformer in the activation of antithrombin by heparin. AB - We have used organic synthesis to understand the role of L-iduronic acid conformational flexibility in the activation of antithrombin by heparin. Among known synthetic analogues of the genuine pentasaccharidic sequence representing the antithrombin binding site of heparin, we have selected as a reference compound the methylated anti-factor Xa pentasaccharide 1. As in the genuine original fragment, the single L-iduronic acid moiety of this molecule exists in water solution as an equilibrium between three conformers 1C4, 4C1 and 2S0. We have thus synthesized three analogues of 1, in which the L-iduronic acid unit is locked in one of these three fixed conformations. A covalent two atom bridge between carbon atoms two and five of L-iduronic acid was first introduced to lock the pseudorotational itinerary of the pyranoid ring around the 2S0 form. A key compound to achieve this connection was the D-glucose derivative 5 in which the H 5 hydrogen atom has been replaced by a vinyl group, which is a progenitor of the carboxylic acid. Selective manipulations of this molecule resulted in the 2S0 type pentasaccharide 23. Starting from the D-glucose derivative 28, a covalent two atom bridge was now built up between carbon atoms three and five to lock the L-iduronic acid moiety around the 1C4 chair form conformation, and the 1C4-type pentasaccharide 43 was synthesized. Finally the L-iduronic acid containing disaccharide 58 which, due to the presence of the methoxymethyl substituent at position five adopts a 4C1 conformation, was directly used to synthesize the 4C1 type pentasaccharide 61. The locked pentasaccharide 23 showed about the same activity as the reference compound 1 in an antithrombin-mediated anti-Xa assay, whereas the two pentasaccharides 43 and 61 displayed very low activity. These results clearly establish the critical importance of the 2S0 conformation of L iduronic acid in the activation of antithrombin by heparin. PMID- 11763452 TI - Conventional and gemini surfactants embedded within bilayer membranes: contrasting behavior. AB - Laser microelectrophoresis (coupled with conductance, fluorescence, and dynamic light scattering) is shown to be a highly instructive tool in comparing the dynamics of conventional and gemini surfactants embedded within vesicle bilayers. The following can be listed among the more important observations and conclusions: a) Cationic conventional surfactant, added to a "solid" (gel) lipid vesicle containing an anionic phospholipid, charge-neutralizes only half the anionic charge. With a "liquid" (liquid crystalline) vesicle, however, the entire negative charge is neutralized. Thus, the cationic conventional surfactant can "flip-flop" readily only in the liquid membrane. b) A cationic gemini surfactant charge-neutralizes only the anionic lipid in the outer membrane leaflet of either solid or liquid membranes, thus indicating an inability to flip-flop regardless of the phase-state of the bilayer. c) Mixed population experiments show that surfactants can hop from one vesicle to another in liquid but not solid membranes. d) In liquid, but not solid, bilayers, a surface-adsorbed cationic polymer can electrostatically "drag" anionic surfactant from the inner leaflet to the outer leaflet where the polymer resides. e) Peripheral fluorescence quenching experiments show that a cationic polymer, adhered to anionic vesicles, can be forced to dissociate in the presence of high concentrations of salt or an anionic polymer. f) Adsorbed polymer, of opposite charge to that imparted to vesicles by a gemini surfactant, is unable to dislocate surfactant even in a liquid membrane. g) In our systems, ionic polymers will not bind to neutral vesicles made solely of zwitterionic phospholipid. On the other hand, ionic polymers bind to neutral vesicles if charge neutrality is obtained by virtue of the membrane containing equimolar amounts of cationic and anionic surfactant. This is attributable to surfactant segregation within the bilayer. h) Experiments prove that polymer migration can occur among a population of neutral ternary vesicles. PMID- 11763453 TI - Polyphenylene dendrimers with perylene diimide as a luminescent core. AB - A novel synthesis is presented of a fourfold ethynyl-substituted perylene diimide dye 4, which acts as a core molecule for the buildup of polyphenylene dendrimers. Around the luminescent core 4, a first-generation (5), a second-generation (6), and a third-generation (7) polyphenylene dendritic environment consisting of pentaphenylbenzene building blocks are constructed. The dendrimers 5 and 6 are synthesized by an exclusively divergent route, whereas for 7, a combination of a divergent and convergent approaches is applied. Absorption and emission spectra of 5-7 in different solvents and in a film have been measured and compared to a nondendronized model compound 13. In solution, the internal chromophore is scarcely influenced by the dendritic scaffold; however, in the solid state, aggregation of the perylene diimide is prevented very effectively by the four rigid dendrons. Additionally, fluorescence quantum yields in solution have been determined for 5-7 and 13; they decrease as the number of generation increases. PMID- 11763454 TI - Quantitative measurements of edge-to-face aromatic interactions by using chemical double-mutant cycles. AB - Synthetic H-bonded zipper complexes have been used to quantify the magnitude of an edge-to-face aromatic interaction between a benzoyl group and an aniline ring. Four chemical double-mutant cycles were constructed by using a matrix of nine closely related complexes in which the aromatic rings were sequentially substituted for alkyl substituents. The stability constants and three-dimensional structures of the complexes were determined by using 1H NMR titrations in deuterochloroform at room temperature. The value of the interaction energy is similar in all cases, the average is -1.4 +/- 0.5 kJ mol(-1). The scope and limitations of the double-mutant approach are explored, and the consequences of conformational equilibria are discussed. PMID- 11763455 TI - A supramolecular system for quantifying aromatic stacking interactions. AB - A supramolecular complex for investigating the thermodynamic properties of intermolecular aromatic stacking interactions has been developed. The conformation of the complex is locked in a single well-defined conformation by an array of H-bonding interactions that force two aromatic rings on one end of the complex into a stacked geometry. Chemical double-mutant cycles have been used to measure an anthracene-aniline interaction (+0.6 +/- 0.8 kJ mol(-1)) and a pentafluorophenyl-aniline interaction (-0.4 +/- 0.9 kJ mol(-1)) in this system. Although the interactions are very weak, the pentafluorophenyl interaction is attractive, whereas the anthracene interaction is repulsive: this is consistent with the dominance of pi-electron electrostatic interactions. The nitropyrrole subunits used to control the conformation of these complexes lead to problems of aggregation and multiple conformational equilibria. The implications for the thermodynamic analysis are examined in detail, and the double-mutant-cycle approach is found to be remarkably robust with respect to such effects, since systematic errors in individual experiments are removed in a pair-wise fashion when the cycle is constructed. PMID- 11763456 TI - Highly selective optical-sensing membranes, containing calix[4]arene chromoionophores, for Pb2+ ions. AB - Plasticized poly(vinyl chloride) (PVC) optode membranes containing novel calix[4]arene chromoionophores 1 or 2 and one equivalent of a lipophilic anion respond to Pb2+ ions with high selectivity over alkali, alkaline-earth, and other heavy metal ions. This selectivity stems from the combination of ligand specificity and a unique ion exchange scheme that employs both monovalent metal ions and protons as the exchanged ions. Complexation of Pb2+ ions inside the membrane is accompanied by deprotonation of the chromoionophores, which causes a bathochromic shift of the absorption maximum lambda(max). The response to Pb2+ ions is modulated by pH and alkali metal ions in a fashion that is consistent with the proposed ion-exchange mechanism. Of all of the other metal ions tested, only Cs+ and Ag+ produce a color change. However, these monovalent metal ions cause hypsochromic shifts of lambda(max) instead of the bathochromic shift caused by Pb2+, because the chromoionophores remain protonated upon complexation. PMID- 11763457 TI - Aurophilic attraction and luminescence of binuclear gold(I) complexes with bridging phosphine ligands: ab initio study. AB - Electronic structure and spectroscopic properties of [Au2(dpm)2]2+ (dpm = bis(diphosphino)methane) were studied by ab initio calculations. The absorption and emission spectra of this binuclear gold(I) complex in acetonitrile and in the solid state were calculated by single excitation configuration interaction (CIS) method. In the calculations, the solvent effect was taken into account by the weakly solvated [Au2(dpm)2]2+ x (MeCN)2 complex. The ground state structures of [Au2(dpm)2]2+ and [Au2(dpm)2]2+ x (MeCN)2 were optimized by the second-order Moller-Plesset perturbation (MP2) method, while the emissive triplet excited state structures were optimized by the CIS calculations. The results reveal that coordination of acetonitrile to the gold atom in the 3[d(sigma*)s(sigma)] excited state causes a significant red shift in emission energy. The weak aurophilic attraction exists in the ground states of [Au2(dpm)2]2+ and [Au2(dpm)2]2+ x (MeCN)2, and is greatly enhanced in their 3[d(sigma*)s(sigma)] excited states. In acetonitrile, the 3Au(s(sigma)) --> 1Ag(d(sigma*)) transition (phosphorescence) of [Au2(dpm)2]2+ was calculated at 557 nm, in consistent with the observed emission of [Au2(dppm)2](ClO4)2 (dppm = bis(diphenylphosphino)methane) at 575 nm. A high energy emission at 331 nm is predicted for [Au2(dpm)2]2+ in the absence of the interaction between the gold atom and solvent molecule and/or neighboring anion in the excited state. The CIS calculations on the excited states also reveal that the two absorption bands at 278 and 218 nm recorded for [Au2(dcpm)2](ClO4)2 in acetonitrile can be attributed to the 1Ag(d(sigma*)) --> 1Au(p(sigma)) and 1Ag(d(sigma*)) --> 1Au((sp)sigma) transitions, respectively. PMID- 11763458 TI - Langmuir and Langmuir-Blodgett films of amphiphilic hexa-peri-hexabenzocoronene: new phase transitions and electronic properties controlled by pressure. AB - We present the synthesis as well as the structural and electronic properties of an amphiphilic derivative of hexaalkylhexa-peri-hexabenzocoronene (HBC), which contains one alkyl substituent that is terminated with a carboxylic acid group. The molecules form well-defined Langmuir films when spread from a solution at the air-water interface. Grazing-incidence X-ray diffraction (GIXD) and X-ray reflectivity studies of the Langmuir monolayer reveal two crystallographic phases at room temperature which depend on the surface pressure applied to the film. Scattering from very well-ordered (zeta = 200-400 A) pi-stacked lamellae of HBC molecules tilted approximately 45 degrees relative to the surface normal is observed in the low-pressure phase. In this phase, the HBC molecules pack in a rectangular two-dimensional unit cell with a = 22.95 A and b = 4.94 A. In the high-pressure phase, coherence from the pi stack is lost. This is a consequence of stress induced by the crystallization of the substituent alkyl chains into a hexagonal lattice, which has a trimerized superstructure in one direction: a = 3 x b = 15.78 A, b = 5.26 A, gamma = 120 degrees, A = 71.9 A2 = 3 x 23.9 A2. Thin monolayer films can be transferred to solid supports by the Langmuir-Blodgett (LB) technique. Atomic force microscopy (AFM) with atomic resolution reveals the crystalline packing of alkyl chains in the high-pressure phase. Kelvin force microscopy (KFM) shows a clear potential difference between the high- and low pressure phases. This is discussed in terms of orbital delocalization (band formation) in the highly coherent low-pressure phase, which is in contrast to the localized molecular orbitals present in the high-pressure phase. The highly coherent pi stack is expected to sustain a very high charge-carrier mobility. PMID- 11763459 TI - Ionic channel structures in [(M+)x([18]crown-6)][Ni(dmit)2]2 molecular conductors. AB - The [(M+)x[18]crown-6)] supramolecular cations (SC+), in which M+ and [18]crown-6 are alkali metal ions (M+ = Li+, Na+, and Cs+) and 1,4,7,10,13,16 hexaoxacyclooctadecane, respectively, form ionic channel structures through the regular stacks of [18]crown-6 in [Ni(dmit)2]-based molecular conductors (dmit2+ = 2-thioxo-1,3-dithiole-4,5-dithiolate). In addition to the [Ni(dmit)2] salts that have the ionic channel structures (these salts are abbreviated as type I salts), Li+ and Na+ form dimerized [(M+)2([18]crown-6)2] units in the crystals (type II salts). The K+ and Rb+ are coordinated tightly into the [18]crown-6 cavity to form typical disk-shape SC+ units in the corresponding [Ni(dmit)2] salts (type III salts). The type I, II, and III salts have typical stoichiometries of [(M+)x([18]crown-6)][Ni(dmit)2]2, [(M+)([18]crown-6)(H2O)x(CH3CN)(1.5 - x)][Ni(dmit)2]3 (x = 1 for Li+ or 0.5 for Na+), and [M+([18]crown 6)][Ni(dmit)2]3, respectively: the salts of the same type are isostructural. In agreement with the trimer structures of [Ni(dmit)2] in the type II and III salts, they exhibit semiconducting behavior with electrical conductivities at 300 K (sigma(300 K)) of 0.01-0.1 S cm(-1). Type I salts contain a regular stack of partially oxidized [Ni(dmit)2] units, which form a quasi one-dimensional metallic band within the tight-binding approximation regime. The electrical conductivities at 300 K are 10-30 S cm(-1), and an almost temperature-independent conductivity was observed at higher temperatures. However, the one-dimensional electronic structures in these salts are strongly influenced by the static and dynamic structures of the coexisting ionic channel. The Na+ salt is a semiconductor, whose magnetic behavior is described by the disordered one-dimensional antiferromagnetic chain. On the other hand, the Cs+ salt is a exhibits metallic properties with 2 kF instability at room temperature. The Li+ salt shows a gradual transition from the high-temperature metallic phase to the low temperature one-dimensional antiferromagnetic semiconductor phase, which was associated with the freezing of Li+ motion at lower temperatures. The preferential crystallization of type I salts was possible by controlling the equilibrium constant (Kc) of the complex formation between M+ ions and the [18]crown-6 molecule. The ionic channel structures were obtained when the KC was low in the electrocrystallization solution, while type II or III salts were formed in the high Kc region. PMID- 11763460 TI - (Phosphanyloxazoline)palladium complexes, part I: (Eta3-1,3 dialkylallyl)(phosphanyloxazoline)palladium complexes: X-ray crystallographic studies, NMR investigations, and quantum-chemical calculations. AB - A series of systematically varied (eta3-1,3-dialkylallyl)palladium complexes of (4S)-[2-(2-diphenylphosphanyl)phenyl]-4,5-dihydrooxazole (PHOX) ligands were characterized by X-ray crystal structure analysis and NMR spectroscopy. Complexes with identical substituents in the 1,3-positions of the allyl group can form eight stereoisomers. In solution four to six isomers were observed and their conformations assigned with the aid of NOE experiments. The dynamic behavior of the complexes was analyzed. In addition, quantum-chemical calculations (restricted Hartree-Fock (HF), density functional theory (DFT)) were carried out and gave satisfactory agreement with experimental findings. PMID- 11763461 TI - Transient-resonance Raman and density functional theory investigation of 4 biphenylylnitrenium, 2-fluorenylnitrenium, and diphenylnitrenium ions. AB - We present transient-resonance Raman spectra for the 4-biphenylylnitrenium, diphenylnitrenium, and 2-fluorenylnitrenium ions. These spectra display a number of fundamental vibrational bands whose frequencies exhibit good agreement with those computed using BPW91/cc-PVDZ density functional theory calculations for the singlet ground states of the 4-biphenylylnitrenium, diphenylnitrenium, and 2 fluorenylnitrenium ions. Comparison of these arylnitrenium ions with each other and with previous results for structurally similar biphenyl radical cations indicates that the degree of iminocyclohexadienyl character observed in these arylnitrenium ions depends on the relative orientation of the two phenyl rings, the nature of the nitrenium ion moiety, and the ability of the biphenyl-like group to accommodate positive charge through formation of a more planar-like structure with quinoidal-like character. PMID- 11763463 TI - Coordination of semiquinone and superoxide radical anions to the zinc ion in SOD model complexes that act as the key step in disproportionation of the radical anions. AB - Reactions of imidazolate-bridged CuII-ZnII heterodinuclear and CuII-CuII homodinuclear complexes, [CuIIZnII(bdpi)(CH3CN)2](ClO4)3 x 2CH3CN (1) and [CuII2(bdpi)(CH3CN)2](ClO4)3 x CH3CN x 3H2O (2) (Hbdpi = 4,5-bis(di(2 pyridylmethyl)aminomethyl)imidazole), with the p-benzosemiquinone radical anion (Q*-) have been examined to provide mechanistic insight into the role of the ZnII ion in copper-zinc superoxide dismutase (Cu,Zn-SOD). The addition of less than one equivalent of Q*- to a deaerated solution of 1 or 2 in propionitrile at -80 degrees C results in the oxidation of Q*- accompanied by the appearance of a new absorption band at 585 nm due to the CuI-Q complex (3 or 4), the absorbance of which increases linearly with the increase in Q*- concentration. Both the resonance Raman spectra of 3 and 4 exhibit a strong resonance-enhanced Raman band at 1580 cm(-1), which can be assigned to a CO stretching vibration in the CuI-Q complexes. Further addition of Q*- to a deaerated solution of 3 in propionitrile results in the reduction of Q*-, whereas no reduction of Q*- occurs with 4, which does not contain the ZnII ion. Thus, the coordination of Q*- to the ZnII ion is essential for the reduction of Q*- by the CuI ion in 3. The coordination of O2*- and Q*- to the ZnII ion has been confirmed by the electronic and ESR spectra of the O2*- and Q*- complexes with mononuclear ZnII complexes, [ZnII[MeIm(Py)2](CH3CN)](ClO4)2 (5) and [ZnII[MeIm(Me)2](H2O)](ClO4)2 (6) (MeIm(Py)2 = (1-methyl-4-imidazolylmethyl)bis(2-pyridylmethyl)amine, MeIm(Me)2 = (1-methyl-4-imidazolylmethyl)bis(6-methyl-2-pyridylmethyl)amine). The binding energies of O2*- with the ZnII ion in 5 and 6 have been evaluated from the deviation of the g values of the ESR spectra from the free spin value. PMID- 11763462 TI - Total synthesis of nucleobase-modified adenophostin A mimics. AB - The adenophostins exhibit approximately 10-100 times higher receptor binding and Ca2+ mobilising potencies in comparison with the natural second messenger D-myo inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Despite many synthetic attempts to determine the minimal structural requirement for this unusual behaviour of the adenophostins, few related simplified analogues displaying higher activity than that of Ins(1,4,5)P3 have been reported. However, biological evaluation of such analogues has revealed that one of the key factors for the enhanced biological activity is the adenine moiety. To further understand the effect that the adenine base has upon the activity of the adenophostins, congeners in which this functionality is replaced by uracil, benzimidazole, 2-methoxynaphthalene, 4 methylanisole and 4-methylnaphthalene using the common intermediate 1,2-di-O acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-alpha-D-glucopyranosyl) ribofuranose have been synthesised using a base replacement strategy. The synthesis of the uracil and benzimidazole analogues was achieved using the Vorbruggen condensation procedure. The 1'-C-glycosidic analogues were prepared using Friedel-Crafts type C-aryl glycosidation reactions. Phosphate groups were introduced using the phosphoramidite method with subsequent removal of all-benzyl protecting groups by catalytic hydrogenation or catalytic hydrogen transfer. Apart from one analogue with an alpha-glycosidic linkage all compounds were more potent than Ins(1,4,5)P3 and most tended more towards adenophostin in activity. These analogues will be valuable tools to unravel the role that the adenine moiety plays in the potent activity of the adenophostins and demonstrate that this strategy is effective at producing highly potent ligands. PMID- 11763464 TI - What is the difference between the manganese porphyrin and corrole analogues of cytochrome P450's compound I? AB - Density functional calculations on oxo-manganese complexes of corrole (1) and porphyrin (2 and 3) show a fundamental difference. The ground state of I is the singlet manganese(V) state, 1A(MnV), in which corrole is a closed shell. In contrast, 2 and 3 have high-spin manganese(IV) states, 1A1u and 3A2u respectively. This difference and the state ordering for each system are rationalized based on the competition between the intrinsic tendency of manganese to prefer high-spin electronic configurations, vis-a-vis the general tendency to prefer double occupancy in the low-lying orbitals. The outcome of this competition is determined primarily by the identity of the macrocycle, corrole versus porphyrin. Corrole with a small cavity holds the MnO moiety with a high off-plane displacement, and thereby prefers the low-spin state. On the other hand, porphyrin with the wider cavity holds the MnO moiety closer to the plane, and thereby prefers high-spin states. PMID- 11763465 TI - Comparative supramolecular chemistry of coronene, hexahelicene, and [18]crown-6: hydrated and solvated molecular complexes of [18]crown-6 with 5 hydroxyisophthalic acid and related di- and tricarboxylic acids. AB - The outer rim of C-H bonds of coronene (COR) and hexahelicene (HEL) is similar to that of the crown conformation of [18]crown-6 (CRO), which is exploited for crystal engineering of molecular complexes of CRO. However, although CRO does form the adduct (TMA)2 x CRO x (H2O)2 (TMA = trimesic acid = 1,3,5 benzenetricarboxylic acid), its structure does not correspond to the H-bonded, three-connected honeycomb sheet architectures of (TMA)2 x COR and (TMA)2 x HEL. Instead, porous, but noninterpenetrating, H-bonded four-connected sheets are observed, with the dihydrated, crown-shaped CRO molecules functioning as spacers rather than molecular guests. In the adduct (CHTA)2 x CRO x (H2O)5 (CHTA = cis,cis-1,3,5-cyclohexanetricarboxylic acid), the tetrahydrated CRO molecules again take up the crown conformation and act as spacers, this time within porous, noninterpenetrating H-bonded three-connected sheets. The engineering goal of CRO filled H-bonded, hexagonal honeycomb cavities similar to the COR- and HEL-filled TMA honeycomb pores in (TMA)2 x COR and (TMA)2 x HEL was met in the adduct (HIPA)6 x CRO x (H2O)10 (HIPA = 5-hydroxyisophthalic acid), crystallized from aqueous EtOH. The crystal structure of this complex is on the one hand built up of isolated hexagonal honeycomb cavities established by six HIPA molecules cyclically linked through pairwise intercarboxylic H bonds. These cavities accommodate the crown-shaped CRO molecules, oriented such that maximally straight C-H...O contacts are enabled between its 12 equatorial H atoms and the surrounding 12 carboxylic groups of HIPA, in complete analogy to the situation prevailing in (TMA)2 x HEL and (probably) (TMA)2 xCOR. The second building block of (HIPA)6 x CRO x (H2O)10 is represented by a centrosymmetric decameric water cluster, which has the connectivity of the carbon skeleton of a bishomocubane with opposite methylene bridges, in agreement with vibrational spectroscopic evidence on gaseous (H2O)10. The crystal architecture of the adduct as a whole may either be likened to a severely distorted NaCl-type lattice, with the (HIPA)6 x CRO units replacing, for example, the Na+ ions, and the water clusters substituting the Cl- ions, or else to a system of stacked host sheets set up by C H...O bonded (HIPA)6 macrorings, which give rise to perpendicular channels taking up guest columns of alternating, H-bonded CRO and (H2O)10 units. Crystals of another, solvated HIPA-CRO adduct of the composition (HIPA)4 x CRO x (EtOH)2 were obtained from aqueous EtOH. Their crystal structure is related to those of (TMA)2 x HEL and (TMA)2 x COR inasmuch distorted HIPA honeycomb sheets are adopted, which may be developed from the hexagonal TMA sheets by replacing one third of the pairwise intercarboxylic linkages by single interphenolic H bonds. The cavities in the HIPA sheets are thus smaller than those of the TMA honeycomb sheets and elliptically shaped. The HIPA sheets associate in pairs yielding twin cavities which take up one CRO and two EtOH molecules. The CRO molecules are suspended in the twin HIPA cages through H bonds extended from the phenolic OH groups and relayed by interposed EtOH "bridges". In keeping with the elliptic shape of the pores in (HIPA)4 x CRO x (EtOH)2, the CRO molecules are not crown shaped, but rather adopt the more rectangular form as observed in crystalline CRO itself. The crystal structure of a dihydrate of HIPA itself was analysed, too, which assembles in a complex three-dimensional H-bonded network. It is finally concluded that hydrated CRO appears to be an avid H-bond acceptor, in particular towards carboxylic acids functioning as H-bond donors. PMID- 11763466 TI - The effects of formulation factors on the moist granulation technique for controlled-release tablets. AB - Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release. PMID- 11763467 TI - X-ray diffraction and electron microscopy in the polymorphism study of ondansetron hydrochloride. AB - Using different techniques, we studied the possible formation of ondansetron polymorphs. Ondansetron is a carbazol antiemetic that acts as a competitive, selective inhibitor of 5-HT3 serotonin receptors. The polymorphs were determined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results suggest that the compounds are not true crystallographic polymorphs, but instead are the product of physical structural changes in the drug, which would be of interest pharmaceutically. PMID- 11763468 TI - Effect of water-soluble polymers on naproxen complexation with natural and chemically modified beta-cyclodextrins. AB - The combined effect of cyclodextrins (CDs) (beta-, methyl-beta-, hydroxypropyl beta-cyclodextrins) and water-soluble polymers (sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone K30, polyethylene glycol 6000) on naproxen solubility improvement was studied. Phase solubility analysis at 25 degrees C was used to investigate the interaction of the drug with each cyclodextrin (or polymer, alone or in the presence of the different water-soluble polymers (or cyclodextrins). The combined use of polymer and cyclodextrin was always clearly more effective in enhancing the aqueous solubility of naproxen in comparison with the corresponding drug-polymer or drug-cyclodextrin binary systems, and the solubilization enhancement was not simply additive, but synergistic. Water-soluble polymers increased the complexation efficacy of cyclodextrins toward naproxen (as shown by the increased stability constants of the complexes), which resulted in enhanced drug solubility. No previous sonication or heating treatments of the drug-cyclodextrin-polymer suspensions was necessary to obtain this favorable effect. The best results were obtained in ternary systems with beta-cyclodextrin, which had a solubilizing effect toward naproxen in the presence of 0.25% w/v of the different hydrophilic polymers examined that was improved from 25% to about 80%, depending on the type of polymer. PMID- 11763469 TI - Evaporative drying of aqueous dispersions of solid lipid nanoparticles. AB - Solid lipid nanoparticles (SLNs) have been proposed as alternative colloidal drug carriers. SLNs are obtained by dispersing warm oil-in-water microemulsions into cold water. The aim of this research was to investigate an evaporative drying process for aqueous dispersions of SLNs. For this purpose, a special apparatus, namely a thermostatic minidesiccator having alumina as the drying medium, was designed to carry out the evaporative drying at a controlled temperature. Besides the water removal kinetics, the mean particle size and the size distribution of SLNs were measured during the during with the aim of detecting the highest temperature at which the drying process can be carried out without significantly affecting the SLN average diameter. The SLN dispersions were evaluated with and without a hydrophilic excipient, commonly used as a cryoprotector (trehalose). The drying temperature of 10 degrees C was found to be the most suitable for obtaining SLNs as a powder, maintaining almost the same size as that of the SLNs in dispersion. PMID- 11763470 TI - Interaction of verapamil hydrochloride with carbopol 934P and its effect on the release rate of the drug and the water uptake of the polymer matrix. AB - In the present study, investigation of the possibility of interaction of verapamil hydrochloride with Carbopol 934P using differential scanning calorimetric analysis and Fourier transform infrared analysis was performed. The effect of the drug-to-polymer ratio, the electrolyte concentration, and the pH of the medium on the extent of interaction of the drug with the polymer using 2(3) factorial design was investigated. The study also investigated the effect of this interaction on the rate of water uptake of the matrix or the rate of release of verapamil hydrochloride from the swelling polymer matrix. Results revealed that the drug-to-polymer ratio had the most influential effect on both the extent of interaction between the drug and the polymer and the rate of water uptake of the polymer matrix. On the other hand, the pH of the medium had the most significant effect on the rate of drug release. Interaction of the tertiary amine nitrogen of the drug with the anionic carboxyl group on the polymer, forming an insoluble complex, reduced the rate of drug release. This interaction also led to neutralization of the carboxyl group and suppression of the electrostatic repulsion between the anionic groups, which reduced the uncoiling and chain relaxation of the polymer and consequently decreased the swelling of the matrix. The application of the designed experiment allowed the quantification of the effect of each of the studied variables on the investigated responses through the calculation of their coefficient in the response suface equation and checking of their significance. PMID- 11763471 TI - Effect of compression force, compression speed, and particle size on the compression properties of paracetamol. AB - The compression characteristics of two particle size fractions (< 90 microm, 105 210 microm) of paracetamol were examined. Each fraction produced extremely weak tablets and displayed a high tendency to cap. Low correlation coefficients of the initial parts of the Heckel plots, a low strain rate sensitivity, and an increase in mean yield pressure (from 34.2 to 45.5 MPa) with decrease in particle size all confirmed that the main mechanism during the compaction of paracetamol was fragmentation. The 105-210-microm particles underwent more fragmentation than the less than 90-microm powder. Heckel analysis confirmed that the larger size fraction of paracetamol produced denser compacts than the smaller fraction. The 105-210-microm fraction resulted in tablets with lower elastic recoveries and elastic energies. The elastic, plastic energy ratios indicated that the majority of energy involved during the compaction of paracetamol was utilized as elastic energy, indicative of massive elastic deformation of paracetamol particles under pressure. PMID- 11763472 TI - A nifedipine coground mixture with sodium deoxycholate. I. Colloidal particle formation and solid-state analysis. AB - Sodium deoxycholate (DCNa) is a bile salt that forms multimolecular inclusion compounds with a variety of organic substances. In this study, complex formulation of DCNa with nifedipine, a poorly water soluble drug, by grinding was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction, differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. A laser diffraction particle size analyzer was also used to determine the particle size distribution curve in solution. When a nifedipine-DCNa (1:2 w/w) mixture coground for 30 min was dispersed into water and a pH 6.8 buffer solution, a semitransparent colloidal solution occurred immediately; 90% of the total particles formed in solution had a diameter less than 600 nm. Both powder X-ray diffraction peaks and DSC endothermic peak of nifedipine crystals were not found for the coground mixture, whereas a new exothermic peak was observed on DSC thermograms. The magnitude of this exothermic peak depended on the weight fraction of DCNa and the grinding time, indicating that nifedipine crystals changed into an amorphous state by complex formation with DCNa during the grinding process. In the FTIR spectrum of the coground mixture, the peaks of aromatic CH out-of-plane bend and dihydropyridine NH stretch of nifedipine were considerably weakened, suggesting that van der Waals interaction may be present between the drug and DCNa molecules. From these results, it is clear that the cogrinding method with DCNa is very useful for the formation of amorphous nifedipine in the solid state and the production of colloidal particles of the drug in solution. PMID- 11763473 TI - A nifedipine coground mixture with sodium deoxycholate. II. Dissolution characteristics and stability. AB - Nifedipine is a poorly water soluble drug that demonstrates low bioavailability. In a previous study, a coground mixture of nifedipine with sodium deoxycholate (DCNa), a bile salt, immediately produced colloidal particles when dispersed in water. In this study, the effect of the weight fraction of DCNa, grinding time, dissolution media, and storage conditions on colloidal particle formation in solution was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction. A laser diffraction particle size analyzer was used to determine the particle size distribution curve in water. The size of particles formed in solution decreased with an increase in the weight fraction of DCNa and grinding time. A nifedipine DCNa (1:2 w/w) mixture coground for 30 min was used in the experiments. Colloidal particle formation from the coground mixture was also observed in dissolution media of water and a pH 6.8 buffer solution at 37 degrees C. Most precipitates passed through a filter with a pore size of 0.8 microm, but the particle size distribution in water was different from that in the pH 6.8 buffer solution. DCNa exhibited not only micellar solubilization for drug crystals, but also a retarding effect on drug crystal growth in a supersaturated solution. The latter effect could serve to form colloidal particles in solution. When stored under 75% relative humidity at 40 degrees C for 1 month, the amorphous coground mixture crystallized, and the particle size in water markedly increased. Therefore, the weight fraction of DCNa, grinding time, dissolution media, and humidity during storage influence the dissolution characteristics of nifedipine from a coground mixture. PMID- 11763474 TI - Synthesis and evaluation of a nonsteroidal anti-inflammatory polymeric prodrug for sustained and site-specific delivery. AB - A new polymerizable drug derivative of diclofenac sodium was synthesized and characterized in terms of melting point, elemental analysis, and infrared spectroscopy. It was then polymerized to obtain a new polymeric prodrug. The prodrug was evaluated for its viscosity, drug content, and in vitro drug release behavior at pH 1.2 and 7.2. The in vitro studies showed that the drug release takes place predominantly at the higher pH and in a sustained manner, as hypothesized. Stability at room temperature, bioavailability, and ulcer-inducing effect of the polymeric prodrug were also studied. The investigations showed complete drug absorption from the polymeric prodrug with a statistically significant decrease in ulcer scoring effect, thus showing its potentialfor site specific and sustained drug delivery. PMID- 11763475 TI - Study of formulation parameters by factorial design in metoprolol tartrate matrix systems. AB - The study of formulation parameters in hydrophilic matrices of metoprolol tartrate by 2(3) factorial design wass made. We compared the dissolution profiles of two hydrophilic polymers (hydroxypropylmethylcellulose and hydroxyethylcellulose) at high and low concentrations and in the presence or absence of an insoluble excipient (calcium hydrogen phosphate dihydrate). The results showed that the presence of an insoluble excipient influenced almost all of the dissolution parameters. PMID- 11763476 TI - Effects of adhesives and permeation enhancers on the skin permeation of captopril. AB - To formulate a transdermal drug delivery system of captopril, monolithic adhesive matrix type patches containing 20% captopril, different pressure-sensitive adhesives, and various permeation enhancers were prepared using a labcoater. The effects of the adhesives and permeation enhancers on skin permeation of captopril from the prepared patches were evaluated using Franz diffusion cells fitted with excised rat skins. The permeation rate of the drug through the excised skin was dependent on the type of polyacrylate copolymers studied. Fatty alcohols resulted in a pronounced enhancing effect on the skin permeation of captopril, while dimethyl sulfoxide, N-methyl-2-pyrrolidone, oleic acid, Transcutol, and polysorbate 20 showed no significant enhancing effect. The permeation-enhancing effect of the fatty alcohols reached the maximum at the level of 100%. Based on these results, a captopril patch may be developed with further optimization. PMID- 11763477 TI - Enhancement of absorption of insulin-loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats. AB - Polyisobutylcyanoacrylate (PIBCA) nanospheres were employed as biodegradable polymeric carriers for oral (p.o.) and subcutaneous (s.c.) delivery of insulin. The polymerization technique used was able to hold 65%-95% of insulin added 30 min after initiation of polymerization. The percentage drug loading was monomer concentration dependent. Insulin adsorption to the nanospheres was measured by radioimmunoassay. Although Pluronic F68 (0.5%) did not significantly alter the in vitro insulin degradation half-life T50%, sodium cholate (0.5%) increased the degradation T50% of insulin by 56% (from 13.6 +/- 1.6 to 22.1 +/- 2 min). This study also investigated the in vivo performance of insulin-loaded PIBCA in aqueous suspension with or without sodium cholate (0.5%) and Pluronic F68 (0.5%) surfactants after oral and subcutaneous administration to alloxan-induced diabetic rats. Insulin absorption was evaluated by its hypoglycemic effect. Insulin associated with PIBCA nanospheres retains its biological activity up to 15 h and 24 h after oral and subcutaneous administrations, respectively. Administered orally insulin-loaded (75 U/kg) nanospheres, in the presence of surfactants, significantly reduced the mean blood glucose level from 392 +/- 32 to 80 +/- 13 mg/dl within 2 h and maintained it at 100 mg/dl or less for more than 8 h. On the other hand, the subcutaneous administration of insulin-loaded (25 U/kg) nanospheres significantly decreased the blood glucose level from 406 +/ 33 to 88.5 +/- 12.8 mg/dl within 1 h, and the lowered glucose level was maintained at 100 mg/dl or less for more than 12 h; it returned to its initial value 24 h after administration. Insulin-loaded nanospheres with surfactants showed significant (P < .05) pharmacological availability (PA%) of 37.6% +/- 3.7% and 65.2% +/- 2.7% after oral and subcutaneous dosages, respectively. The existence of surfactants with PIBCA nanospheres improved the oral PA% by 49.2%. These findings suggest that the developed PIBCA, in the presence of surfactants, would be useful not only in improving insulin gastrointestinal absorption, but also in sustaining its systemic action by lowering the blood glucose to an acceptable level. PMID- 11763478 TI - Study of the theophylline content of single coated particles by gas chromatography/mass spectrometry. AB - The aim of the present study was to determine by gas chromatography/mass spectrometry (GC/MS) the content uniformity of single theophylline microcapsules of different particle size ranges. Microencapsulation was carried out in a laboratory fluidized bed system using Eudragit L30D aqueous dispersion. Scanning electron microscopy was applied for the characterization of the surface morphology of the prepared theophylline microcapsules of two different particle size ranges. The theophylline content of single particles was determined by GC/MS analysis. It was found that the particle size of microcapsules greatly influenced their theophylline content. The GC/MS analysis was successully applied to indicate the changes in the content uniformity and thus the interparticular costing distribution of single theophylline microcapsules in the presence of several excipients. PMID- 11763479 TI - Stability of 4-DMAP in solution. AB - A stability-indicating reversed-phase performance liquid chromatographic method was developed for the detection of 4-(N,N-dimethylamino)phenol (4-DMAP) and its degradation products under accelerated degradation conditions. The degradation kinetics of 4-DMAP in aqueous solution over a pH range of 1.12-6.05 and its stability in solutions based on propylene glycol or polyethylene glycol 400 were investigated. The observed rate constants were shown to follow, apparent first order kinetics in all cases. The pH rate profile shows that maximum stability of 4-DMAP was observed in the pH range 2.0 to 3.0. Acid/base catalysis of 4-DMAP was not affected by systems of various ionic strengths. Incorporation of nonaqueous propylene glycol or polyethylene glycol 400 in the pH 3.05 solution of 4-DMAP showed an increase in the stability at 55 degrees C +/- 0.5 degrees C. PMID- 11763480 TI - Potential pulmonary effects of man-made organic fiber (MMOF) dusts. AB - In the first half of the twentieth century epidemiologic evidence linked elevated incidences of pulmonary fibrosis and cancer with inhalation of chrysotile and crocidolite asbestos, a family of naturally occurring inorganic fibrous materials. As the serpentine and amphibole forms of asbestos were phased out, synthetic vitreous fibers (SVFs; fiber glass, mineral wool, and refractory fiber) became increasingly utilized, and concerns were raised that they too might cause adverse health effects. Extensive toxicological research on SVFs has demonstrated that their pulmonary effects are directly related to fiber dose in the lung over time. This is the result of deposition (thin fibers deposit in the lower lung more efficiently than thick fibers) and lung-persistence ("biopersistence" is directly related to fiber length and inversely related to dissolution and fragmentation rates). In rat inhalation studies, asbestos was determined to be 7- to 10-fold more biopersistent in the lung than SVFs. Other than its effect on biopersistence, fiber composition did not appear to play a direct role in the biological activity of SVFs. Recently, the utilization of man-made organic fibers (MMOFs) (also referred to by some as synthetic organic fibers) has increased rapidly for a variety of applications. In contrast to SVFs, research on the potential pulmonary effects of MMOFs is relatively limited, because traditionally MMOFs were manufactured in diameters too thick to be respirable (inhalable into the lower lung). However, new developments in the MMOF industry have resulted in the production of increasingly fine-diameter fibers for special applications, and certain post-manufacturing processes (e.g., chopping) generate respirable-sized MMOF dust. Until the mid-1990s, there was no consistent evidence of human health affects attributed to occupational exposure to MMOFs. Very recently, however, a unique form of interstitial lung disease has been reported in nylon flock workers in three different plants, and respirable-sized nylon shreds (including fibers) were identified in workplace air samples. Whether nylon dust or other occupational exposures are responsible for the development of lung disease in these workers remains to be determined. It is also unknown whether the biological mechanisms that determine the respirability and toxicity of SVFs apply to MMOFs. Thus, it is appropriate and timely to review the current data regarding MMOF workplace exposure and pulmonary health effects, including the database on epidemiological, exposure assessment, and toxicology studies. PMID- 11763481 TI - Carcinogenic risk of toluene diisocyanate and 4,4'-methylenediphenyl diisocyanate: epidemiological and experimental evidence. AB - Diisocyanates are highly reactive compounds widely used, for example, in the production of polyurethane foams, elastomers, paints, and adhesives. The high chemical reactivity of these compounds is also reflected in their toxicity: diisocyanates are one of the most important causes of occupational asthma but also other adverse effects, such as irritation and toxic reactions, have been described in exposed subjects. One of the open questions is whether occupational isocyanate exposure is a carcinogenic hazard. The few epidemiological studies available have been based on young cohorts and short follow-up and are not conclusive. Toluene diisocyanate (TDI) has been classified as carcinogenic in animals on the basis of gavage administration studies, but no conclusions are available on inhalation exposure. For 4,4'-methylene diphenyldiisocyanate (MDI) there is suggestive evidence for carcinogenicity in rats. The possible carcinogenic mechanism of TDI and MDI is not clear. Both chemicals have been positive in a number of short-term tests inducing gene mutations and chromosomal damage. The reactive form could be either the diisocyanate itself or may derive from the metabolic activation of the aromatic diamine derivatives formed by hydrolysis. TDI and MDI react with DNA in vivo and in vitro. However, the structure of the adducts has not been identified. Especially from the in vivo experiment it is not known if the adducts are a product from the reaction with the isocyanate or the corresponding amine. In conclusion, both TDI and MDI are highly reactive chemicals that bind to DNA and are probably genotoxic. The alleged animal carcinogenicity of TDI and MDI would suggest that occupational exposure to these compounds is a carcinogenic risk. The few epidemiological studies available have not, however, been able to clarify if TDI and MDI are occupational carcinogens. PMID- 11763482 TI - Holmium laser resection of the prostate (HoLRP): 2-year follow-up data. AB - PURPOSE: The aim of this study was to evaluate the 2-year clinical outcome of patients who underwent holmium laser resection of the prostate (HoLRP) for management of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: All patients who underwent HoLRP before October 1995 were contacted by mail. Each patient completed an American Urological Association (AUA) symptom score index, a questionnaire, and a urinary flow rate. The questionnaire was used to evaluate the frequency of complications, incontinence, recatheterization, and patient satisfaction. RESULTS: Two hundred twelve patients were contacted and 168 responded. Of these, 100 patients successfully completed all three investigations and had all preoperative information available. Mean length of follow-up was 27.5 months (range 24 to 34 months). Mean peak urinary flow was 21.6 mL/s (range 6 to 34 mL/s), mean voided volume was 348 mL (range 146 to 1,387 mL), and mean AUA symptom score index was 6.8 (range 0 to 27). Eighty-eight percent of patients stated they would have HoLRP again for management of their BPH. The perioperative recatheterization rate was 9%. Reoperation rate with a minimum of 2 years of follow-up was 5%; three patients required a bladder neck incision and two patients required a revision HoLRP. Urethral strictures occurred in 4% of patients, and 1% of patients had persistent incontinence requiring pads. CONCLUSIONS: Medium-term clinical results of HoLRP confirm that patient satisfaction is excellent, with complication rates similar to those historically reported for transurethral resection of the prostate (TURP). The HoLRP technique is an effective and durable surgical alternative to standard TURP. PMID- 11763483 TI - Results of treatment with tamsulosin in men with acute urinary retention. AB - PURPOSE: The aim of this study was to prospectively assess the outcome in men treated with temporary catheter drainage and tamsulosin after an episode of acute urinary retention (AUR). MATERIALS AND METHODS: Thirty-three consecutive men with AUR were treated with tamsulosin 0.4 mg daily for at least 4 days before a trial of voiding. Those men who were able to void adequately continued taking tamsulosin and were evaluated at 2-week and 3-month follow-up. After 3 months, additional follow-up was obtained at regular intervals as determined by the treating physician. RESULTS: Median follow-up was 6.5 months. Mean urine volume at the time of initial bladder drainage was 790 mL. Eighty-eight percent (29/33) of men were able to void initially. Transurethral prostatectomy or intermittent catheterization were necessary in 9 (27%) of 33 patients during the follow-up period. A poor quality-of-life score on the initial International Prostate Symptom Score (p = .038) and a high postvoid residual volume 2 weeks after catheter removal (p = .013) correlated with failure of medical therapy. Patients with AUR after nonurologic surgery had a significantly better outcome than those with AUR that did not occur postoperatively. Mean symptom score, quality-of-life score, and postvoid residual urine volume were 12.9, 2.7, and 111 mL, respectively, at 2-week follow-up and were 11.9, 2.8, and 61.7 mL, respectively, at 3-month follow-up. Mean peak urinary flow rate at 3 months was 7.7 mL/s. CONCLUSIONS: Tamsulosin appears to be helpful in the management of men with AUR. The majority of men were able to avoid surgery after temporary catheter drainage. PMID- 11763485 TI - Obliterated urethra: holmium:yttrium-aluminum-garnet cut-to-light with urolume stenting. AB - Antegrade-retrograde urethrotomy, or the cut-to-light procedure, performed for obliterated urethra is associated with a high rate of recurrence of urethra] stricture. With the goal of reducing the stricture recurrence rate, we performed a modified cut-to-light procedure using a holmium:yttrium-aluminum-garnet laser and UroLume stenting in a 76-year-old man with urethral obliteration. PMID- 11763484 TI - United States experience with tension-free vaginal tape procedure for urinary stress incontinence: assessment of safety and tolerability. AB - PURPOSE: The tension-free vaginal tape (TVT) procedure is an operation for treatment of stress urinary incontinence. A polypropylene mesh tape is placed to support the midurethra through a small vaginal incision. In this study, we present our preliminary results evaluating the safety, tolerability, and perioperative morbidity of this procedure. MATERIALS AND METHODS: One hundred patients with stress urinary incontinence underwent the TVT procedure as part of an observational study. Patients were evaluated prospectively with history and pelvic examination, urodynamic studies, perioperative protocol, outcome and satisfaction questionnaire, and postoperative visits at 3 weeks and 2 months. RESULTS: The procedure was performed with the patient under local anesthesia, using intravenous sedation in 97 patients and regional anesthesia in 3. Mean surgical time was 35.5 minutes. Bladder penetration occurred in 24 patients. Forty-two required overnight urethral catheterization. Mean hospital stay was 0.18 days. By 24 hours after the procedure, 95% were able to void. At 3-week follow-up, 88% of patients were completely continent and 9% significantly improved. CONCLUSIONS: The TVT procedure for stress urinary incontinence is a safe, minimally invasive operation with minimal perioperative morbidity. Considering these preliminary findings and long-term European data of 1 to 3 years' experience with continence rate averaging 85%, the TVT procedure may prove to be the operation of choice to treat stress urinary incontinence for many women. PMID- 11763486 TI - Coagulating intermittent cutting: improved high-frequency surgery in transurethral prostatectomy. AB - PURPOSE: Despite the good long-term results of transurethral resection of the prostate (TURP), intraoperative blood loss and TUR syndrome produce morbidity. Thus, TURP is still considered invasive therapy. Many minor invasive alternative treatment modalities have been developed in recent years. MATERIAL AND METHODS: To minimize the risk of bleeding, we have improved on the high-frequency technology. The output signals of commercially available high-frequency generators were modulated such that each cut results in an efficient coagulation zone in the tissue with excellent cutting quality. RESULTS: Laboratory and in vitro studies using porcine kidneys as well as clinical trials showed good cutting characteristics accompanied by a significant reduction of bleeding. As a result, blood transfusions were less necessary, TUR syndrome occurred less often, the indwelling catheter could be removed earlier in the postoperative period, and hospitalization time was reduced. CONCLUSIONS: We believe that this improved high frequency technology, termed coagulating intermittent cutting, results in blood sparing tissue resection and reduction of morbidity. PMID- 11763487 TI - Renal ultrasound changes after internal double-J stented pyeloplasty for ureteropelvic junction obstruction. AB - PURPOSE: Renal ultrasound changes after pediatric pyeloplasty were reported recently in the literature, mainly on unstented pyeloplasties. We evaluated the time to improvement or resolution of hydronephrosis in pediatric patients who underwent double-J stented pyeloplasty for ureteropelvic junction (UPJ) obstruction and compared our results to unstented pyeloplasties. MATERIALS AND METHODS: Ultrasonic grading of hydronephrosis after double-J stented pyeloplasty was performed according to the Society for Fetal Urology criteria at intervals of 0 to 3. 3 to 6, 6 to 12, and greater than 12 months postoperatively. Twenty-six pyeloplasties met all criteria for inclusion. The median patient age was 4 months. RESULTS: Of the 26 pyeloplasties studied, 18 kidneys had grade 4, 7 grade 3, and I grade 2 hydronephrosis. Twenty-two percent of kidneys with grade 4 hydronephrosis had resolution of pyelocaliectasis at the 0- to 3-month ultrasound examination; all of these kidneys had the stents removed prior to being studied. No patient with improvement of hydronephrosis worsened on subsequent examinations. All but three patients improved over 1-year follow-up: 11 (42%) to grade 0, 5 (19.2%) to grade 1, 6 (23%) to grade 2, and 1 (3.8%) to grade 3. The average final grade was 1.56 for grade 4 and 0.57 for grade 3 hydronephrosis. This represented more rapid improvement than unstented pyeloplasties. Average indwelling time for double-J stent was 52 days. CONCLUSIONS: Improvement and sometimes resolution of hydronephrosis after internal double-J stented pyeloplasty for UPJ obstruction is rapid and can occur within the first 3 months postoperatively. One year postoperatively, the majority of renal units have grade 2 hydronephrosis or less. We recommend the use of indwelling double-J ureteral stents in all pediatric patients undergoing dismembered pyeloplasty for UPJ obstruction to allow for more rapid improvement and possible resolution ofpyelocaliectasis. Further comparison of stented vs. unstented pyeloplasty is needed. PMID- 11763488 TI - Effective renal plasma flow calculated from a single blood sample following Technetium-99m mercaptoacetyltriglycine renal scan can predict delayed graft function in renal transplantation. AB - PURPOSE: Effective renal plasma flow (ERPF) can be calculated by obtaining a single blood sample at a fixed time after injection in a patient undergoing a technetium-99m mercaptoacetyltriglycine (99mTc MAG3) renal scan. The purpose of this study was to determine whether the calculated ERPF following cadaveric renal transplantation could accurately predict the need fordialysis within the first 10 postoperative days or the serum creatinine at postoperative day 10. MATERIALS AND METHODS: Between February 1994 and September 1998, 41 patients underwent 45 99mTc MAG3 renal scans within the first 10 days following a cadaveric renal transplantation at Harbor-UCLA Medical Center. A blood sample was drawn 44 minutes after injection of 99mTc and was used to calculate ERPF. This calculated ERPF was compared to measures of early function, such as the need for dialysis and serum creatinine. RESULTS: Decreased ERPF strongly correlated with the need for dialysis within the first 10 postoperative days (p < .0001). No patient with ERPF >210 mL/min/1.7 M2 required dialysis, whereas 35% (6/17) of patients with ERPF < or =210 mL/min/1.7 M2 required dialysis within the first 10 postoperative days. For those patients who did not undergo dialysis, the calculated ERPF was significantly related to the serum creatinine on postoperative day 10 (p<.0001 ). CONCLUSIONS: ERPF can be calculated from a single blood sample when performing a 99mTc MAG3 renal scan following cadaveric renal transplantation. This calculated ERPF provides a useful clinical tool to identify patients at high risk for development of delayed graft function. PMID- 11763490 TI - Combined Doppler, blood gas, and Bennet quick test for venous leak practical for prepenile prosthesis testing in solo private offices. AB - Cavernosal blood gases have been widely reported but have not become routine in private practice. The method reported here employs the aspiration of blood gases 15 minutes after pharmacologic challenge followed by a quick test for venous leak followed by Doppler stethoscope observations. The results in 90 patients suggest its selective use in the subset of nonresponding, nonleakers who have open cavernous arteries by Doppler, typically diabetics. PMID- 11763489 TI - Interstitial laser therapy for benign prostatic hyperplasia in the anticoagulated patient. AB - PURPOSE: Interstitial laser therapy (ILT) was performed without discontinuing warfarin anticoagulation therapy in eight patients (mean international normalized ratio 2.8 +/- 0.8) with benign prostatic hyperplasia. Three patients were in urinary retention and had failed voiding trials. Five had severe symptoms (mean American Urological Association symptom score 22 +/- 7) and had failed medical therapy. MATERIALS AND METHODS: Interstitial laser therapy was performed using the Indigo model 830e LaserOptic Treatment System with the patient under local anesthesia. Mean operative time was 25 minutes and mean total laser energy was 6,785 J. RESULTS: After surgery, spontaneous voiding was achieved by 7 of the 8 patients at 1 week and by all 8 patients at 3 weeks. At 3-month follow-up, mean American Urological Association symptom score was 13 +/- 5, and mean peak urinary flow rate had increased to 12.2 +/- 3.2 mL/s from 8.8 mL/s (excluding retention) before surgery. Interstitial diode laser therapy appears to be a safe and effective technique for treatment of benign prostatic hyperplasia in the fully anticoagulated patient. PMID- 11763491 TI - Crural ligation surgery for the young male with venogenic erectile dysfunction: technique. AB - Isolated crural venous leak is an uncommon cause of erectile dysfunction. Recent data have suggested that ligation of the crura in men with this condition may result in significant improvement in erectile function. This report outlines the criteria for patient selection and the technique we use to accomplish crural ligation. PMID- 11763492 TI - Postradiation prostatic sarcoma: de novo carcinogenesis or dedifferentiation of prostatic adenocarcinoma? AB - Postradiation sarcoma (PRS) of the prostate is rare. We describe the second case associated with brachytherapy for adenocarcinoma and review the literature on prior cases of PRS as well as carcinosarcoma, a dedifferentiated form ofadenocarcinoma that may be confused with true prostate sarcoma. It is clear that radiation to the prostate confers a significantly increased risk for subsequent sarcoma, although not within the prostate. Because many of the reported cases of PRS were admixed with adenocarcinoma and had relatively short latency periods, we conclude that these cases of PRS ofthe prostate are, in fact, carcinosarcoma. Therefore, with only one case reported following therapeutic irradiation, PRS of the prostate is extremely rare. PMID- 11763493 TI - Treatment of giant ancient pelvic schwannoma. AB - A 32-year-old patient presented with urinary retention and chronic constipation. Computerized tomography and magnetic resonance imaging showed a 10 x 11cm encapsulated tumor with cystic areas lying ventral to the sacrum. There was no evidence of invasion of bladder or rectum. At laparotomy, a 10 x 11 cm mass was found in the left pelvis. Final pathology revealed an ancient schwannoma. In most large series, 80% to 90% of the primary retroperitoneal tumors are malignant. Retroperitoneal schwannomas can be benign or malignant, roughly half of the reported cases showed malignancy. Benign schwannomas may arise along the course of any myelinated nerve, with the acoustic neuroma being the most frequent site. Immunostaining showed a strong expression of S-100 protein. The staining for this protein is helpful for differentiation of a benign schwannoma from a malignant peripheral nerve sheath tumor and from other benign spindle cell tumors. The treatment of choice for benign schwannomas is complete excision. Recurrence or persistence seems to be associated with incomplete resection, which occurred in 10% of the reported cases. After surgery, the patient had normal erection, normal micturition, and normal defecation but no symptoms of motor and sensory disturbances. PMID- 11763494 TI - Lower pole ureteral obstruction secondary to fecal impaction in an 8-year-old girl. AB - An 8-year-old girl presented with frequent, nonfebrile, urinary tract infections and a lifelong history of severe constipation. Ultrasound revealed bilateral duplicated renal systems, severe right upper pole hydronephrosis, and moderate left lower pole hydronephrosis. Computerized tomographic scan revealed a large, fecal-impacted colon. Diuretic renogram showed high-grade obstruction (T1/2 >30 minutes) of the right upper pole and left lower pole moieties. After administering an aggressive bowel preparation, a repeat diuretic renogram was performed, which revealed resolution of the left lower pole obstruction. Constipation has long been established as a contributing factor to urinary tract infections in children. However, fecal impaction causing ureteral obstruction in a child has not been reported. We report the case of an 8-year-old girl who had left lower pole ureteral obstruction secondary to fecal impaction. PMID- 11763495 TI - 31-Year-old bladder diverticulocutaneous fistula with a giant stone as a complication of pelvic fracture. AB - Pelvic fractures associated with urinary bladder rupture are not rare, however, bladder fistulae are a rare complication after primary repair of bladder rupture. To our knowledge, we present the first case of a vesical diverticulocutaneous fistula after pelvic fractures. Etiology, presentation. diagnosis, and management are discussed. PMID- 11763496 TI - Effect of circumcision on prostatic bacterial colonization and subsequent bacterial seeding following transrectal ultrasound-guided prostate biopsies. AB - PURPOSE: This study was designed to compare the prevalence of prostatic bacterial growth between circumcised and uncircumcised males and determine whether the lack of circumcision results in a change in the incidence of bacterial seeding following prostate needle biopsy. MATERIALS AND METHODS: Forty-six men (21 circumcised and 25 uncircumcised) undergoing ultrasound and biopsy to rule out prostate cancer were evaluated with questionnaires regarding previous history of urinary tract infection (UTI), any symptoms suggestive of UTI, and obstructive voiding symptoms. None of the patients received preprocedure antibiotics. Preprocedure and postprocedure urine samples, prostate biopsy core, and postprocedure blood samples were obtained for culture. After the cultures were obtained, patients received oral antibiotics. RESULTS: Patient characteristics between circumcised and uncircumcised patients were similar in terms of age, prostate-specific antigen level, voiding symptoms, history of UTI, prostate biopsy technique, and incidence of prostate cancer. The prevalence of preprocedure bacteriuria was slightly higher in the uncircumcised men (14 [56%] of 25 patients) vs. the circumcised men (8/21 [38%] patients), although this was not statistically significant (r = .2, p = .1). The prevalence of postprocedure bacteriuria was significantly higher (p = .04) in the uncircumcised men (12/25 [48%] patients) vs. the circumcised men (4/21 [19%] patients). No correlation was found between circumcision status and incidence of bacterial colonization in the prostate tissue. A statistically significant difference (p = .003) was found between the lack of circumcision and postprocedure bacteremia. CONCLUSIONS: Circumcision status does not effect the prevalence of bacterial growth in the urine and the prostate tissue. Uncircumcised men have a higher incidence of bacteriuria and bacteremia following prostate needle biopsies. PMID- 11763497 TI - Pulsatile drug-delivery systems. AB - Delivery systems with a pulsatile-release pattern are receiving increasing interest for the development of drugs for which conventional controlled drug release systems with a continuous release are not ideal. These drugs often have a high first-pass effect or special chronopharmacological needs. A pulsatile release profile is characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Pulsatile drug-delivery systems can be classified into site-specific systems in which the drug is released at the desired site within the intestinal tract (e.g., the colon), or time-controlled devices in which the drug is released after a well-defined time period. Site controlled release is usually controlled by environmental factors, like the pH or enzymes present in the intestinal tract, whereas the drug release from time controlled systems is controlled primarily by the delivery system and, ideally, not by the environment. This review covers various single- and multiple-unit oral pulsatile drug-delivery systems with an emphasis on time-controlled drug-release systems. PMID- 11763498 TI - Multifunctional matrices for oral peptide delivery. AB - The oral administration of peptide drugs represents one of the greatest challenges in pharmaceutical technology. To gain a sufficient bioavailability of these therapeutic agents, various barriers including the mucus-layer barrier, the enzymatic barrier, and the membrane barrier have to be overcome. A promising strategy for achieving this goal is the use of multifunctional matrices. These matrices are based on polymers that display mucoadhesive properties, a permeation enhancing effect, enzyme-inhibiting properties, and/or a high buffer capacity. Moreover, a sustained or delayed drug release can be provided by delivery systems that contain such polymers. Among them, polyacrylates, cellulose derivatives, and chitosan are promising excipients that can also be customized by chemical modification to improve certain properties. For example, the covalent attachment of thiol moieties on these polymers leads to improved mucoadhesive and permeation enhancing properties, and the conjugation of enzyme inhibitors enables the matrices to provide protection for peptide drugs against enzymatic degradation. The efficacy of multifunctional matrices in oral peptide delivery has been verified by various in vivo studies that could pave the way for the development of commercially viable formulations. PMID- 11763499 TI - Transcutaneous immunization: an emerging route of immunization and potent immunostimulation strategy. AB - Transcutaneous immunization (TCI) has emerged recently as a new method of vaccination that uses the skin. The simplicity of a patch-based immunization may obscure the potency of this strategy for immunostimulation because TCI allows the safe use of a wide variety of potent adjuvants. It is thought that these adjuvants activate Langerhans cells in the skin, which migrate to the draining lymph to orchestrate robust systemic immune responses. TCI represents a novel combination using established knowledge relating to skin penetration, the potency of adjuvant-based immunostimulation, and data showing that Langerhans cells are highly desirable targets because of their antigen-presenting cell function. The near-term challenge will be to take this promising insight into successful product development. PMID- 11763500 TI - Primary Sjogren's syndrome and keratoconjunctivitis sicca: diagnostic methods, frequency and social disease aspects. PMID- 11763501 TI - Microbial production of spider silk proteins. AB - The remarkable properties of spider dragline silk and related protein polymers will find many applications if the materials can be produced economically. We have demonstrated the production of high molecular weight spider dragline silk analog proteins encoded by synthetic genes in several microbial systems, including Escherichia coli and Pichia pastoris. In E. coli, proteins of up to 1000 amino acids in length could be produced efficiently, but the yield and homogeneity of higher molecular weight silk proteins were found to be limited by truncated synthesis, probably as a result of ribosome termination errors. No such phenomenon was observed in the yeast P. pastoris, where higher molecular weight silk proteins could be produced without heterogeneity due to truncated synthesis. Spider dragline silk analog proteins could be secreted by P. pastoris when fused to both the signal sequence and N-terminal pro-sequence of the Saccharomyces cerevisiae alpha-mating factor gene. PMID- 11763502 TI - Lessons from nature--protein fibers. AB - Silks are protein fibers with remarkable mechanical properties. The discovery of the structural features that govern these properties is a challenge for biochemistry and structural biology. This review summarizes the results of the biochemistry of silk proteins as well as the knowledge of the molecular biology of the respective genes. In addition, an overview is presented on the efforts to produce recombinant silk proteins by biotechnological techniques. PMID- 11763503 TI - Silk biotechnology. PMID- 11763504 TI - Strength and structure of spiders' silks. AB - Spider silks are composite materials with often complex microstructures. They are spun from liquid crystalline dope using a complicated spinning mechanism which gives the animal considerable control. The material properties of finished silk are modified by the effects of water and other solvents, and spiders make use of this to produce fibres with specific qualities. The surprising sophistication of spider silks and spinning technologies makes it imperative for us to understand both material and manufacturing in nature before embarking on the commercialization of biotechnologically modified silk dope. PMID- 11763505 TI - Molecular biology of spider silk. AB - Spider silks are an intriguing family of fibrous proteins due to their highly repetitive primary sequence, their solution properties and their assembly and processing into fibers with remarkable mechanical properties. Current research efforts aimed at understanding and manipulating genes encoding these proteins are helping to gain insight into the relationships between protein sequence, protein assembly and macromolecular properties. PMID- 11763506 TI - New silk protein: modification of silk protein by gene engineering for production of biomaterials. AB - The interest in silk fibroin morphology and structure have increased due to its attractiveness for bio-related applications. Silk fibers have been used as sutures for a long time in the surgical field, due to the biocompatibility of silk fibroin fibers with human living tissue. In addition, it has been demonstrated that silk can be used as a substrate for enzyme immobilization in biosensors. A more complete understanding of silk structure would provide the possibility to further exploit silk fibroin for a wide range of new uses, such as the production of oxygen-permeable membranes and biocompatible materials. Silk fibroin-based membranes could be utilized as soft tissue compatible polymers. Baculovirus-mediated transgenesis of the silkworm allows specific alterations in a target sequence. Homologous recombination of a foreign gene downstream from a powerful promoter, such as the fibroin promoter, would allow the constitutive production of a useful protein in the silkworm and the modification of the character of silk protein. A chimeric protein consisted of fibroin and green fluorescent protein was expressed under the control of fibroin in the posterior silk gland and the gene product was spun into the cocoon layer. This technique, gene targeting, will lead to the modification and enhancement of physicochemical properties of silk protein. PMID- 11763507 TI - [The impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on planning of radiotherapy]. AB - AIM: To determine the impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on patient management in radiotherapy. MATERIAL AND METHODS: One hundred sixty-nine consecutive patients with different malignant tumors were analyzed. Whole-body FDG-PET was performed for staging before radiotherapy. The strategy of radiotherapy before and after PET scanning was compared and the change in the treatment management determined. RESULTS: In 47(28%) of 169 patients PET results changed patient management in radiotherapy. In 19 patients (11%) radiotherapy was not performed after PET. In 16 patients (10%) PET results changed the intention of radiation treatment (curative/palliative). Correction of radiation dose was made in 16 patients (10%). Correction of the volume of the exposure area was made in 12 patients (7%). Tumor outside the field of view was missed in only 2 patients with a regional PET scan. CONCLUSION: In this retrospective analysis the information provided by FDG-PET contributes to a substantial change in radiotherapy strategy. PMID- 11763508 TI - [How physicians and patients look at the problem of obesity]. AB - AIM: To elicit attitude of physicians and population to the problem of obesity; to assess awareness and diagnostic and therapeutic tool. MATERIAL AND METHODS: A questionnaire survey was performed among 384 endocrinologists and 54 other medical professional in 13 cities of Russia. 1405 randomly selected citizens of Moscow (males and females) aged 18-64 years were interviewed according to the standard questionnaire on the telephone. THE RESULTS: Opinion of the physicians. Endocrinologists think that the key factors of weight gain are the following: overeating (81%), hypodynamia (53%), heredity (36%), endocrine pathology (20%), diet rich in fat (18%). Body weight is assessed on the basis of BWI (80%), weight height tables (38%), Brock's formula (25%), waist and hip circumferences (21%). Endocrinologists believe that obesity should be treated to improve wellbeing (75%), concomitant syndromes (53%), appearance (4%). 92% of endocrinologists recommend a low-calory diet, 82%--physical exercise, 15%--medication, 6%--food additives. Potential patients. 1/3 of city population have overweight. 1/4 of them want to lose weight. Women want to lose weight three times more frequently than men. The proportion of men and women wanting to lose weight is higher at the age group of 40-49 years. Obese subjects more frequently than subjects with normal weight want to lose weight without keeping diet (53 vs 39%) or extra physical activity (38% vs 27%). Women more frequently use methods of losing weight (both registered and unregistered). CONCLUSION: Physicians underestimate the role of obesity in genesis of concomitant diseases, the role of high-calory diets in development of obesity. Most of potential patients have an inadequate attitude to the necessity and feasibility of weight loss, are unrealistic as to methods of losing weight and effectiveness of such methods. PMID- 11763509 TI - [Primary generalized amyloidosis: a case report]. PMID- 11763510 TI - [Gestational diabetes mellitus (a literature review)]. PMID- 11763511 TI - [Renal and uterine hemodynamics in pregnant women with hypertension]. AB - AIM: To study gestational alterations of renal and uterine hemodynamics, their relationships with systemic and intracardiac hemodynamics in pregnant women (PW) with essential hypertension (EH). MATERIAL AND METHODS: Echocardiography, ultrasound dopplerography of renal and uterine arteries, roll-over test were made in the course of trimester II-III and 3 months after the delivery in 48 PW with EH degree 1-2 and control 20 healthy PW. Hemodynamic parameters in pregnancy were compared to postpartum ones. The latter were supposed to be basal. RESULTS: Changes in systemic and intracardiac hemodynamics in EH and control women were in many respects similar but systolic blood pressure in EH changed insignificantly, minute volume increased owing to increased heart rate. PW with EH of the second degree have in the III trimester more frequent positive roll-over test this evidencing for high pressor reactivity of the vascular system. PW with EH showed higher speed of the blood flow in the renal arteries in unchanged resistance. With growing gestation time the resistance of the uterine arteries declined. The resistance of the main stem of the renal artery went up in enhanced cardiac contraction regardless of total peripheral vascular resistance (TPVR). Blood flow in the uterine arteries worsened in elevation of arterial pressure, TPVR, lowering of the heart rate and systolic function of the heart. Renal and uterine hemodynamics were independent. CONCLUSION: Hemodynamic changes in control and EH PW were similar in many respects but higher arterial pressure, abnormal systolic function of the left ventricle, bradycardia disturb uterine blood flow. Renal circulation was independent of systemic and intracardiac hemodynamics and is unrelated to changes in the uterine circulation. PMID- 11763512 TI - [Hormone replacement therapy in women with arterial hypertension in peri- and postmenopause: hemodynamic effects]. AB - AIM: To study hemodynamic effects of replacement hormone therapy (RHT) with trisecvens, beta-blocker betaksolol and their combination in perimenopausal and menopausal women with hypertension. MATERIAL AND METHODS: The study was made of 60 menopausal women aged 45-60 with mild and moderate arterial hypertension (AH). The women had no contraindications to either RHT or beta-blockers. They were randomized into three groups: group 1 received trisekvens, group 2--trisekvens plus betaksolol in a dose 10-20 mg/day, group 3--betaksolol. Arterial pressure (AP) and heart rate (HR) were measured before the treatment, in one month and each three months for a year. ECG and echo-CG were registered before treatment and each 3 months of the therapy. AP monitoring covered 50% of the patients of each group before the treatment and after 1 and 3 months of it. The data were analysed according to SAS system. RESULTS: Group 1 patients showed no significant changes in AP and HR. Group 2 and 3 patients' AP lowered, in group 2 the fall of systolic AP being more pronounced. 12-month therapy brought about a 10.3% decrease in left ventricular myocardial mass index in group 2. CONCLUSION: RHT with trisekvens in combination with beta-blocker in long-term use potentiates the effect on systolic AP and reduced hypertrophy of the left ventricle. RHT does not produce a significant effect on AP in women with AH recorded before the menopause. PMID- 11763513 TI - [Effect of the treatment with femoston on the cardiovascular system in postmenopausal women]. AB - AIM: To assess femoston effects on the cardiovascular system in postmenopause. MATERIAL AND METHODS: Cardiovascular effects of femoston were studied in 20 postmenopausal women with menopausal syndrome. 70% patients had arterial hypertension. Cardiovascular system was examined before the treatment and after three treatment months using 24-h monitoring of arterial pressure, echocardiography, photoplethysmography, conjunctival biomicroscopy, central hemodynamics tests. RESULTS: In the course of femoston treatment menopausal manifestations relieved, arterial pressure was lowering. 3-month treatment has improved parameters of central and peripheral hemodynamics: total peripheral vascular resistance significantly fell, stroke and minute blood volumes, cardiac indexrose, tissue blood flow and microcirculation improved. CONCLUSION: Femoston produces positive changes in cardiovascular system, vascular tone, microcirculation and arterial pressure. PMID- 11763514 TI - [Characteristics of mental status of patients with neurocirculatory dystonia]. AB - AIM: To specify forms of severity of mental disorders in neurocirculatory asthenia (NCA) for more precise differentiation between NCA as a nosological entity and syndrome. MATERIAL AND METHODS: The examination including specially designed interview, ECG, echo-CG, orthostatic and hyperventilation tests, bicycle exercise, consultation of the psychiatrist, psychological tests covered 80 NCA patients (31 men, 49 women, mean age 29.2 +/- 9.08 years). RESULTS: NCA is characterized by the absence of a clear link with psychoemotional stress, seasonal disease aggravations, weakness, dizziness, negative results of orthostatic and hyperventilation tests. Among NCA criteria, dominating are "additional signs". Patients with anxio-fobic, panic, anxio-depressive neurotic disorders are characterized by strong relations between manifestation, subsequent disease exacerbations with psychogenia; attack-like NCA manifestation, prevalence of "basic signs" among diagnostic criteria (cardialgia, pulse and blood pressure lability, nonspecific alterations of T wave, positive orthostatic and hyperventilation tests). CONCLUSION: NCA presents at least with two variants. In the first variant NCA picture is characterized by hereditary or early acquired vegetative stigmation and secondary neurotic disorders; the second variant presents as a clinically formed illness in which NCA symptoms manifest as a syndrome which is a leading component of a mental disease. PMID- 11763515 TI - [Treatment of asthenic disorders with tanakan]. AB - AIM: To evaluate efficacy and safety of tanakan in different asthenic disorders. MATERIAL AND METHODS: Tanakan in a dose 240 mg/day was used in 60 patients with various asthenic disorders arising in neurasthenia and late after craniocerebral trauma. The response was assessed by the scale of general clinical impression, side effects and by changes in psychic and somatic status. RESULTS: The response was achieved in 90% of the patients. 78% had significant improvement regardless nosological entity of asthenia. CONCLUSION: Tanakan is safe and effective in therapy of asthenic disorders. Moreover, with tanakan asthenia can be treated without polypragmasia. PMID- 11763516 TI - [Immune correction by polyoxidonium in chronic alcoholics with renal impairement]. AB - AIM: To study clinical effectiveness and immunocorrective properties of polyoxidonium in chronic alcoholics with renal impairment. MATERIAL AND METHODS: The trial enrolled 62 chronic alcoholics with chronic pyelonephritis (CP). Group 1 comprised 28 patients (mean age 39.9 +/- 2.4 years) with severe chronic alcoholism (CA) in long abstinence and grave CP; 16 moderate CA patients of group 2 (mean age 42.2 +/- 1.2 years) with moderate CP in drinking period; the control group consisted of 11 severe CA patients (mean age 39.2 +/- 1.2 years) in short term abstinence and moderate CP. CP was the only visceral damage in the examinees. All the patients were examined clinically. Biochemical blood tests, ultrasound, x-ray examinations, radionuclide investigation of the kidneys, immunological examination were made before and after the treatment. Patients of groups 1 and 2 received polyoxidonium (12 mg once a day, i.m., each other day, a course dose 0.084 g) in combination with penicillin and nistatin. Patients of group 3 received placebo in combination with the same antibacterial therapy. RESULTS: Remission with normalization of laboratory and immunological parameters was achieved in 75% of group 1 patients. No response was seen in 7.1%. In group 2 remissions were absent while immunological changes were insignificant. Group 3 patients exhibited clinical response in 48.2% but no remission was achieved. CONCLUSION: Polyoxidonium immunocorrection was effective in CA patients with renal affection only in long-term abstinence being a failure in drinking period. PMID- 11763517 TI - [Errors in diagnosis and treatment in lung neoplasms]. PMID- 11763518 TI - [New developments in phytotherapy of chronic prostatitis (a lecture)]. PMID- 11763519 TI - [Tropacin in the treatment of patients with the hyperactive urinary bladder]. AB - AIM: To examine effectiveness and tolerance of tropacin in patients with hyperactive urinary bladder (HAUB). MATERIAL AND METHODS: 62 patients aged between 19 and 82 with hyperactive bladder have received tropacin in a dose 3-10 mg twice a day for 12 weeks. Of them 31 had idiopathic detrusor unstability (IDUS), 10 had sensory urgent disorders (SUD), 21 suffered from detrusor hyperreflexia (DHR). RESULTS: In IDUS patients 12-week tropacin administration reduced mean daily number of urination from 14.3 to 10.9, mean daily number of episodes of inperative enuresis diminished from 3.9 to 2.2. DHR patients showed the above decrease from 15.2 to 12.7 and 4.1 to 2.2, respectively. In sensory urgency tropacin was less effective. CONCLUSION: Tropacin is effective and safe medicine for treatment of IDUS and DHR. PMID- 11763520 TI - [DNA-abzymes and their clinical significance in systemic lupus erythematosis]. AB - AIM: To evaluate occurrence of DNA-abzymes with catalytic (DNA-hydrolysing) and cytotoxic properties in patients with systemic lupus erythematosus (SLE) for examination of clinical value of DNA-abzymes in diagnosis of autoimmune syndrome and apoptosis level in different variants of immunopathology. MATERIAL AND METHODS: The study group consisted of patients with verified SLE diagnosis (n = 120). They were compared to 72 patients with rheumatoid arthritis (RA), 82 patients with scleroderma systematica (SS), 60 patients with discoid lupus erythematosus (DLE), 88 patients with focal scleroderma (FS) and 198 autoimmune uveitis (AU) patients. 128 donors served control. Catalytic and cytotoxic activity of DNA-abzymes were determined by methods of molecular biology and enzymology. All the patients were examined for blood levels of IgG, IgM and IgA, anti-DNA, anti-Sm and other IgG-autoantibodies, CIC titers, phagocyting activity, content of main D-cell subpopulations. Key immunoregulatory indices were also estimated. RESULTS: DNA-abzymes were detected more often in SLE and RA patients. In SLE, catalytic and cytotoxic activities of DNA-abzymes reached their maximum. There was a correlation with leading clinicoimmunological signs of SLE. The disease was most severe with apparent immunopathology in patients with maximal catalytic and cytotoxic activity of DNA-abzymes. With lowering cytotoxic activity of DNA-abzymes more patients demonstrate low SLE activity without severe organic lesions and alleviated symptoms of immunopathology. CONCLUSION: An important role of DNA-abzymes in pathogenesis of SLE is shown. They are also valuable tools in diagnosis of various clinicoimmunological variants of the disease. PMID- 11763521 TI - [Antioxidant and antiarrhythmic activity of carvedilol in patients with ischemic heart disease. Comparison with anaprilin]. AB - AIM: To examine antioxidant and antiarrhythmic activity of carvedilol vs that of standard beta-blocker anaprilin in coronary patients with low left ventricular ejection fraction (LVEF). MATERIAL AND METHODS: The cross-over trial enrolled 50 coronary male patients with LVEF under 45%. Before and after treatment with carvedilol and anaprilin, measurements were made of blood dienic conjugates and malonic dialdehyde, 24-h ECG monitoring was performed. RESULTS: The antioxidant activity of antiarrhythmic effect of carvedilol was significantly higher than that of anaprilin. A correlation was discovered between the number of extrasystoles and blood levels of dienic conjugates. CONCLUSION: Marked antioxidant activity of carvedilol as well as reduced myocardial energy consumption resultant from hemodynamic cardiac unloading due to block of alpha adrenoreceptors contribute to carvedilol additional antiarrhythmic effect. PMID- 11763522 TI - [Pumpan in the treatment of ischemic heart disease associated with arterial hypertension]. AB - AIM: To study effectiveness of natural combined medicine pumpan in patients with ischemic heart disease (IHD) including cases with concomitant arterial hypertension (AH). MATERIAL AND METHODS: 35 patients with different forms of IHD (myocardial infarction, stable and unstable angina pectoris of functional class III-IV) received conventional treatment combined with pumpan given for 7-11 weeks. Changes in clinical condition, biochemical blood indices, ECG, echo-CG, 24 h arterial pressure monitoring data were investigated. RESULTS: The addition of pumpan to the standard therapy reduced frequency of anginal attacks, improved intracardiac hemodynamics, psychic and adaptive indices. CONCLUSION: Pumpan is a good adjuvant to conventional treatment of various IHD forms including combination of IHD with AH. Pumpan enables reduction in the required doses of beta-blockers, ACE inhibitors, nitrates, sedatives. It also provides hypocoagulatory and hypocholesterolemic effect. PMID- 11763524 TI - [Comparative safety of treatment of arterial hypertension with calcium antagonists: a problem of evidence ( a lecture)]. PMID- 11763523 TI - [Changes in blood rheological properties in patients with hypertension]. AB - AIM: To study hemorheology in patients with essential hypertension (EH), to improve EH treatment in terms of blood rheology. MATERIAL AND METHODS: Blood rheology, microcirculation, lipid plasm spectrum, central hemodynamics were studied in 90 patients with mild and 83 patients with moderate or severe EH as well as 30 healthy controls before and after treatment (hypotensive drugs, essential phospholipids, intravenous laser blood radiation, plasmapheresis). RESULTS: Hemorrheological disorders (subnormal deformability of the red cells and elastoviscosity of their membranes, disk-spherical transformation and hyperaggregation of blood cells, high dynamic viscosity) correlated with the disease severity, arterial pressure and total peripheral vascular resistance. Long-term (1-1.5 years) hypotensive therapy, especially with combination of beta blockers with diuretics, has a negative effect on blood rheology. Optimisation of EH treatment in terms of blood rheology consists in using essential phospholipids in stable hypertension, intravenous laser radiation in complicated hypertension, plasmapheresis in drug-resistant hypertension. Such an approach not only significantly improves hemorheology but also provides good clinical and hypotensive effects in 75-80% patients. CONCLUSION: Blood viscodynamics should be taken into consideration in individual treatment of hypertensive patients. PMID- 11763525 TI - [Correction of sleep disorders and efficacy of antihypertensive monotherapy in elderly patients: use of ivadal]. AB - AIM: To assess effects of ivadal (zolpidem) on arterial pressure (AP) in the cycle sleep-awake in aged patients with insomnia who have failed hypotensive monotherapy with different drugs, i.e. whose AP remained abnormal at night. MATERIALS AND METHODS: The trial included 25 aged patients (17 females, 8 males, mean age 66.4 +/- 3.7 years) with isolated systolic arterial hypertension (AH) of the first-second degree (WHO classification, 1999) and insomnia. AH duration averaged 8.7 +/- 3.7 years. All the patients have received antihypertensive monotherapy. As shown by the initial 24-h monitoring, patients with elevated night AP had significantly lower mean score by the questionnaire "Subjective Sleep Characteristics" and more frequently suffer from insomnia. These patients were given a hypnotic drug ivadal (zolpidem) in a single daily dose 5 mg in the evening for 10 days. On the treatment night 10 monitoring of AP was repeated. RESULTS: Ivadal treatment has significantly improved all the subjective parameters of sleep and 24-h AP profile, lowered sleep and awake AP. CONCLUSION: Ivadal treatment raises efficacy of a hypotensive monotherapy in aged patients with isolated systolic AH and insomnia. PMID- 11763526 TI - [Use of ednit in the treatment of portal hypertension in patients with chronic hepatitis and liver cirrhosis]. AB - AIM: To study ednit (ACE inhibitor) effectiveness in the treatment of portal hypertension in patients with chronic hepatitis (CH) and hepatic cirrhosis (HC). MATERIAL AND METHODS: The examination of 87 patients with active CH and 54 patients with HC at the preascytic stage included two-dimentional ultrasonic scanning of the abdominal organs with doppler fluometry of the vessels in the territory of the portal vein, tetrapolar rheohepatography, ultrasound investigation, angiography of the abdominal vessels. The patients received combined therapy with ednit in a dose 5 mg twice a day for at least 5 weeks. RESULTS: Patients with active CH and HC having portal hypertension treated with adjuvant ednit in the above dose achieved marked clinicobiochemical remission quicker, portal-hepatic circulation improved. CONCLUSION: The addition of ednit to therapy of active CH and HC with portal hypertension is effective as it lowers total peripheral vascular resistance which eventually results in a fall of pressure in the territory of the portal vein and improvement of hepatic circulation. The highest effect is reached in administration of 5 mg twice for 24 hours. PMID- 11763527 TI - [Influence of sodium pump and Na(+), K(+), CL(-)-cotransport on the resting membrane potential of somatic muscle cells of the earthworm Lumbricus terrestris]. AB - Tetrodotoxin and acidic pH do not change the resting membrane potential (RMP), whereas Na+ or Cl- free solutions or ouabain and furosemide equally depolarize the membrane of the earthworm somatic muscle cells. The findings of the RMP depending on extracellular K+ concentration corroborate theoretical model by Goldman-Hodgkin-Katz only in Na(+)-free medium or in presence of ouabain. The data suggest that the RMP is the sum of potassium and chlorine diffusion potentials as well as of the potential produced by electrogenic component of Na+ pump and, probably, by furosemide-sensitive Na+,K+Cl- co-transport. PMID- 11763528 TI - [Initiation of locomotor activity in spinalized cats by epidural stimulation of the spinal cord]. AB - An area initiating locomotor activity under conditions of the spinal cord surface stimulation (SCS) was found at the upper border of the lumbar enlargement (L4-5 spinal segments). Parameters of the SCS for activation of the spinal stepping generator (SSG) were identified. Activation of the SSG under the SCS was shown to occur because of interaction of the spinal and peripheral mechanisms. Primary role in the SSG initiation during the SCS belongs to the propriospinal system of the dorsolateral funiculi. PMID- 11763529 TI - [The role of stress proteins HSP70 and the adrenergic system in different resistance to myocardial infarction of August and Wistar genetic rat strains]. AB - A lesser resistance against myocardial infarction (MI) in the Wistar rats as compared with the August rats was found to be combined with a greater stress response and activation of the heart sympathetic regulation in the former rats. In the Wistar rats and not in August rats, an activation of hypothalamic noradrenaline (NA) system occurs as well as a greater "output" of the NA from sympathetic terminals in the myocardium. Accumulation of the HSP 70 stress proteins in IM in the myocardium is nearly 2-2.5-fold lesser in the Wistar rats. Thereupon, different resistance against the IM in Wistar and August rats seems to be due to a genetically determine differences in intensity of the stress response, activation of the heart sympathetic regulation in the IM, and production of the HSP 70 protective stress-proteins in the myocardium. PMID- 11763530 TI - [Dependence of the size of leukocytes on their number in human blood]. AB - An interaction was shown to exist among the quantities of neutrophiles, lympho- and monocytes in circulation and characteristics of their corpuscular volume. The correlation embraces all the leukocyte classes, being apparent in indices of separate classes as well as on the intertype level. Such a co-ordination is involved in maintenance of the normal microcirculation level and manifested in a series of intra- and intertype correlations of relative content and parameters of the corpuscular volume distribution of the cells. PMID- 11763531 TI - [Effect of the water deprivation during pregnancy on the water-salt tissue composition and kidney function in the rat offspring of the first and second generation]. AB - Rats were subjected to intermittent water restriction from the 1st day of pregnancy until delivery. Water, sodium, and potassium contents in the liver, brain, skeletal muscles, heart, kidneys, and subcutaneous fat tissue were determined in the litter. Water and sodium contents in 30-day old rats of the 1st and 2nd generation were found to be comparable to the control values. Water loading resulted in weaker diuretic responses in the former rats as compared with the control. No differences in the renal response were revealed in adult rats. PMID- 11763532 TI - [Changes in the neuroendocrine regulation of adaptive behavior in rats subjected to stress in the late prenatal ontogenesis]. AB - Female rats were subjected from the 14th to 17th day of pregnancy to immobilisation under conditions of 1-hour daily bright illumination. On the 20th day, contents of testosterone and estradiol was decreased with no sex difference in their level in the pregnant female rats' blood and in the amniotic fluid. Sex differences were flattened in 1-month litter both in the androgen and oestrogen contents and in adaptive behaviour. In prenatally stressed males, motor activity was inhibited and anxiety was enhanced as compared with the control. At one and a half months of age, the consequences of the prenatal stress disappeared and then reappeared after sexual maturation but with an opposite trend. Adaptive behaviour of adult males was less flexible and revealed no age-dependent oscillations inherent in the control animals. Prenatal stress while preventing the maximal raise of sex steroids in the blood shifts sex differentiation of the adaptive behaviour toward demasculinization. PMID- 11763533 TI - [Effect of physical load on serum protein glycation in rats with induced diabetes]. AB - Decreased levels of early and advanced glycation products were found in exercise training diabetic rats as compared with sedentary diabetic rats. Adaptation to systemic physical exercise in diabetic animals affects not only enzyme-regulated metabolism but also non-enzymatic processes involving protein glycation. PMID- 11763534 TI - [Adaptation to hyperthermia and changes in peripheral blood leukocytes in humans]. AB - Heating humans up to rectal temperature 39.0-39.5 degrees C induces a heat stress and a physiological adaptation. Blood cells were found to produce nitric oxide under these conditions, neutrophiles playing a major role in the process. In our opinion, the HSC 70 takes part in the process of the long cell adaptation augmenting the cells' functional activity. Hyperthermia leads to a massive temporal HSP 72 expression in the blood mononuclears. This expression seems to be due to alterations in the cellular proteins and to oxidative stress. PMID- 11763536 TI - [Factor analysis of interrelations between EEG waves with various frequency ranges in adults and 5-6 year old children]. AB - Statistical interrelations among different amplitude-temporal features of the EEG waves of different frequency bands in adults and 5-6-year old children are determined mainly by two factors. The first one is related to the alpha-wave index and amplitude and the beta-wave index, the second one--to the alpha-wave average period. Adults revealed a higher level of negative correlation between the EEG wave amplitude and index and the theta-wave index than the 5-6-year old children. PMID- 11763535 TI - [Neurochemical characteristics of the ventromedial hypothalamus and anti-aversive effects of anxiolytic agents in various anxiety models]. AB - Neurochemical analysis using anxiosedative and anxioselective agents injected into the hypothalamus revealed that antiaversive action of camprione is only realised under conditions of domineering fear motivation whereas that of chlordiazepoxide, phenibut, indoter may also be realised under conditions of negative stressful zoo-social impacts mediated by serotonin. PMID- 11763537 TI - [Behavioral disorders caused by acute and chronic manganese intoxications of white rats]. AB - Single per oral administration of manganese chloride induced an obvious reversible diminishing of locomotor activity in white rats as well as deterioration of avoidance response to unconditioned and conditioned stimuli, prolongation of the conditioning latency, and a temporary deterioration of learning. Chronic manganese intoxication produced an irreversible learning disability and a slight memory disorders. PMID- 11763538 TI - [Effect of estrous cycle phase on pain threshold in female white rats]. AB - Pain thresholds and body resistance in female Wistar rats were determined during estrous cycle stages. The flinch and shuffle thresholds were increased on the 3rd day of measurement in diestrus and estrus but not in proestrus and metestrus as compared with the thresholds during the 1st day of recording. The thresholds decreased as of the 7th day to the 14th day. Daily threshold measurements raised the body resistance on the 7th day of recording. In contrast to the pain thresholds, the body resistance change had not a stage-dependent character. PMID- 11763539 TI - [Autoregulation of coronary vessels following the acute blood loss and its combination with preexisting immobilization stress]. AB - A 6-hour immobilization stress and a 2-hour posthaemorrhagic hypotension caused elevation of the coronary flow, deterioration of coronary autoregulation, decreasing of the coronary dilation reserve, and diminishing of the left ventricular pressure. In the "stress + haemorrhage" group, the changes of the coronary vessels autoregulation ability were less obvious. Concentration of NO3 /NO2- in the blood serum was elevated after stress. Inhibition of the NO-synthase decreased the coronary flow. Thereupon, a pre-existing immobilization stress alters the coronary vessels tone. PMID- 11763540 TI - [Ability of novel non-competitive glutamate receptor blocking agents to weaken motor disorders in animals]. AB - Action of mono- and dication derivatives of phenylcyclohexyl was compared with effects of known NMDA-antagonists memantine and dizocilpine. Seizures induced with the NMDA were effectively prevented both by mono- and dications, whereas against the kainate seizures dication alone was effective. Anticataleptic activity was much stronger in monocations, and the side effect of the substances under study on motor co-ordination was obviously weaker than in dizocilpine. Thereupon, the phenylcyclohexyl derivatives might be regarded as potential means for treatment of parkinsonism and other motor disorders. PMID- 11763541 TI - [Effect of long-term restraint stress on behavior of female C57BL/6J and CBA/Lac inbred mice. Dispersion and cluster analysis]. AB - An augmented exploratory behaviour and motor activity and diminished anxiety after a restraint stress were found in CBA/Lac female mice [corrected] but not in C57BL/6J ones. In the Porsolt test the result was exactly opposite. A possibility of inherent anxiety-depressive pathological condition in the C57BL/6J mice [corrected] developing under the effect of repeated psychological stress, is assumed. PMID- 11763542 TI - Influence function based variance estimation and missing data issues in case cohort studies. AB - Recognizing that the efficiency in relative risk estimation for the Cox proportional hazards model is largely constrained by the total number of cases, Prentice (1986) proposed the case-cohort design in which covariates are measured on all cases and on a random sample of the cohort. Subsequent to Prentice, other methods of estimation and sampling have been proposed for these designs. We formalize an approach to variance estimation suggested by Barlow (1994), and derive a robust variance estimator based on the influence function. We consider the applicability of the variance estimator to all the proposed case-cohort estimators, and derive the influence function when known sampling probabilities in the estimators are replaced by observed sampling fractions. We discuss the modifications required when cases are missing covariate information. The missingness may occur by chance, and be completely at random; or may occur as part of the sampling design, and depend upon other observed covariates. We provide an adaptation of S-plus code that allows estimating influence function variances in the presence of such missing covariates. Using examples from our current case-cohort studies on esophageal and gastric cancer, we illustrate how our results our useful in solving design and analytic issues that arise in practice. PMID- 11763543 TI - Dynamic random effects models for times between repeated events. AB - We consider recurrent event data when the duration or gap times between successive event occurrences are of intrinsic interest. Subject heterogeneity not attributed to observed covariates is usually handled by random effects which result in an exchangeable correlation structure for the gap times of a subject. Recently, efforts have been put into relaxing this restriction to allow non exchangeable correlation. Here we consider dynamic models where random effects can vary stochastically over the gap times. We extend the traditional Gaussian variance components models and evaluate a previously proposed proportional hazards model through a simulation study and some examples. Besides, semiparametric estimation of the proportional hazards models is considered. Both models are easily used. The Gaussian models are easily interpreted in terms of the variance structure. On the other hand, the proportional hazards models would be more appropriate in the context of survival analysis, particularly in the interpretation of the regression parameters. They can be sensitive to the choice of model for random effects but not to the choice of the baseline hazard function. PMID- 11763544 TI - Nonparametric test for doubly interval-censored failure time data. AB - This paper considers comparison of discrete failure time distributions when the survival time of interest measures elapsed time between two related events and observations on the occurrences of both events could be interval-censored. This kind of data is often referred to as doubly interval-censored failure time data. If the occurrence of the first event defining the survival time can be exactly observed, the data are usually referred to as interval-censored data. For the comparison problem based on interval-censored failure time data, Sun (1996) proposed a nonparametric test procedure. In this paper we generalize the procedure given in Sun (1996) to doubly interval-censored data case and the generalized test is evaluated by simulations. PMID- 11763546 TI - Comparison of confidence procedures for type I censored exponential lifetimes. AB - In the model of type I censored exponential lifetimes, coverage probabilities are compared for a number of confidence interval constructions proposed in literature. The coverage probabilities are calculated exactly for sample sizes up to 50 and for different degrees of censoring and different degrees of intended confidence. If not only a fair two-sided coverage is desired, but also fair one sided coverages, only few methods are quite satisfactory. A likelihood-based interval and a third root transformation to normality work almost perfectly, but the chi 2-based method that is perfect under no censoring and under type II censoring can also be advocated. PMID- 11763545 TI - A method for estimating time dependent intervention benefits under arbitrarily varying age and exogenous components of hazard. AB - A method for estimating the dependence of intrinsic intervention benefits on time elapsed since the intervention took place is proposed. The method is aimed at intervention programs against diseases where one or all of the following components of hazard intensity may undergo important and unknown variations: 1) the intervention benefits to a subject are a function of the time elapsed since the intervention took place, or since inception for a continuing treatment, 2) the subjects vulnerability is an unknown function of their age, 3) the exogenous or environmental baseline intensity, to which all are assumed subjected, fluctuates arbitrarily with calendar time. During the time span of a study, these variables interact in a complex way, possibly masking the real contribution of the intervention. However, with very general assumptions about how hazard components interact, the cumulative hazards of subpopulations treated at different times in the past are shown to be described mathematically by a convolution of the time elapsed dependent intervention benefit function with the age and calendar time dependent baseline intensity. Starting from the cumulative hazards of untreated and treated subpopulations that had the intervention at different times in the past, a method of deconvolution through regularization is proposed to reconstruct the time elapsed dependence of the intervention benefit function. The regularization technique used is of the 'penalized least square smoothing' type, it is applied to the solution of Volterra integral equations of the first kind under noisy inputs. Simulations, to test for the reconstruction of different modes of time elapsed variation of the intervention benefits, are carried out on realistically noisy 'data sets' taken to be available at a limited number of time points. The stability of the estimated reconstructions, to measurement errors, is examined through repeated simulations with random noise added to inputs. The method is applied to a Brazilian data set where BCG vaccination resulted in a small reduction in the cumulated risk of leprosy infection. PMID- 11763547 TI - Smooth estimation of the reliability function. AB - Problems with censored data arise quite frequently in reliability applications. Estimation of the reliability function is usually of concern. Reliability function estimators proposed by Kaplan and Meier (1958), Breslow (1972), are generally used when dealing with censored data. These estimators have the known properties of being asymptotically unbiased, uniformly strongly consistent, and weakly convergent to the same Gaussian process, when properly normalized. We study the properties of the smoothed Kaplan-Meier estimator with a suitable kernel function in this paper. The smooth estimator is compared with the Kaplan Meier and Breslow estimators for large sample sizes giving an exact expression for an appropriately normalized difference of the mean square error (MSE) of the two estimators. This quantifies the deficiency of the Kaplan-Meier estimator in comparison to the smoothed version. We also obtain a non-asymptotic bound on an expected L1-type error under weak conditions. Some simulations are carried out to examine the performance of the suggested method. PMID- 11763548 TI - Multilevel models for meta-analysis, and their application to absolute risk differences. AB - Meta-analysis can be considered a multilevel statistical problem, since information within studies is combined in the presence of potential heterogeneity between studies. Here a general multilevel model framework is developed for meta analysis to combine either summary data or individual patient outcome data from each study, and to include either study or individual level covariates that might explain heterogeneity. Classical and Bayesian approaches to estimation are contrasted. These methods are applied to a meta-analysis of trials of thrombolytic therapy after myocardial infarction. Subgroups within the trials were available, categorized by the time delay until treatment, so that a three level random effects model that includes time delay as a covariate is proposed. In addition it was desired to represent the treatment effect as an absolute risk reduction, rather than the conventional odds ratio. We show how this can be achieved within a Bayesian analysis, while still recognizing the binary nature of the original outcome data. PMID- 11763549 TI - Estimating effects of latent and measured genotypes in multilevel models. AB - Multilevel modelling is a data analysis technique for analysing linear models in samples with a hierarchical or clustered structure. Clustered data are often present in genetic research where family members may either be required or serve a methodological purpose to study hereditary factors. These samples imply a natural hierarchy because genetically related individuals are grouped within families. We first demonstrate the use of multilevel modelling to study latent genetic and environmental components of variance in extended families where subjects may be related as twins, full siblings, half siblings, or cousins. Next, measured genotypes are included to estimate locus effects. Because the model accounts for the clustering of observations by estimating a random intercept at the family level, it tests for genotype effects on the phenotype within families so that possible population stratification effects cannot cause false positive results. Several extensions are discussed such as testing for genotype environment interactions, analysing different types of response scales, or tailoring the model to other sample structures. To illustrate the approach we used birth weight data of 5562 children from 3643 fathers from 3186 mothers in 2873 extended families to which simulated genotypes of a hypothetical locus were added. PMID- 11763550 TI - Multilevel models for censored and latent responses. AB - Multilevel models were originally developed to allow linear regression or ANOVA models to be applied to observations that are not mutually independent. This lack of independence commonly arises due to clustering of the units of observations into 'higher level units' such as patients in hospitals. In linear mixed models, the within-cluster correlations are modelled by including random effects in a linear model. In this paper, we discuss generalizations of linear mixed models suitable for responses subject to systematic and random measurement error and interval censoring. The first example uses data from two cross-sectional surveys of schoolchildren to investigate risk factors for early first experimentation with cigarettes. Here the recalled times of the children's first cigarette are likely to be subject to both systematic and random measurement errors as well as being interval censored. We describe multilevel models for interval censored survival times as special cases of generalized linear mixed models and discuss methods of estimating systematic recall bias. The second example is a longitudinal study of mental health problems of patients nested in clinics. Here the outcome is measured by multiple questionnaires allowing the measurement errors to be modelled within a linear latent growth curve model. The resulting model is a multilevel structural equation model. We briefly discuss such models both as extensions of linear mixed models and as extensions of structural equation models. Several different model structures are examined. An important goal of the paper is to place a number of methods that readers may have considered as being distinct within a single overall modelling framework. PMID- 11763551 TI - Multilevel analysis with messy data. AB - This paper reviews applications of the method of multiple imputation to dealing with multilevel data that have several kinds of imperfections. These are classified into two broad categories: missing values and imprecise measurement (corrupted recording). The role of the model describing the data imperfections is emphasized. With multiple imputation, these imperfections and information about the processes underlying them can be taken into account. The inferences drawn exploit all the collected information and appropriately reflect the information contained in the data. PMID- 11763552 TI - [Organizational-methodological approaches to treating tuberculosis in children and adolescents in the growth of an endemic disease]. AB - The paper presents guidelines in treating tuberculosis in children from the experience gained in Russia and other foreign countries. Emphasis is laid on the necessity of applying a comprehensive approach to the treatment whose main constituents are sanitary and dietary regimens, etiotropic and pathogenetic therapies, prevention of exacerbations or treatment of concomitant diseases. It is important to use antituberculous agents rationally by determining a standard treatment regimens for patients with various somatic diseases. Of great value is the pattern of organization of a therapeutical process at different stages (institutional treatment at a hospital, day hospital, or sanatorium and outpatient treatment), which secures continuity and accordingly enhances the efficiency of treatment as a whole. PMID- 11763553 TI - [Effectiveness of the standard mode of chemotherapy for newly-diagnosed patients with destructive pulmonary tuberculosis with bacterial isolation]. AB - The authors evaluated the efficiency of a routine drug therapy regimen by the WHO category 1 in treating 149 new cases of destructive pulmonary tuberculosis and bacterial isolation. They used not only the WHO sputum smear negativization criterion, but the data of cultural studies and on lung cavernous closure. The specific features of the approach applied were compulsory cultural studies determining Mycobacterium sensitivities before treatment and compulsory correction of chemotherapy after there was evidence for the sensitivity. Retrospective analysis of 6-month chemotherapy has ascertained that the efficiency of the routine drug therapy regimen largely depends on the baseline extent of infiltrative and destructive changes in the lung and on the baseline resistance of Mycobacteria tuberculosis. They showed a high baseline resistance to streptomycin (20.6%) and streptomycin and isoniazid (33.1%) and a low baseline resistance to ethambutol (5.1%). In these cases, the more optimum regimen was a combination of rifampicin, pyrazanamide, and ethambutol. When Mycobacteria showed multidrug resistance, the routine regimen was ineffective and caused amplification to a larger number of drugs. A modified treatment course using the routine regimen in the intensive phase was developed. If Mycobacterial resistance was present, compulsory correction was made by using reserve agents, pathogenetic treatments, artificial pneumothorax or surgical interventions, which made it possible to abacillate 94.1% of patients by their smears and culture by months 4 5 and to close caverns in 91.3% of cases by months 8-10. PMID- 11763554 TI - [Local ozone therapy in the complex surgical treatment of pulmonary and pleural tuberculosis patients]. AB - The found bactericidal activity of ozone and oxygen mixture containing ozone, 10 mg/l, and ozoned solutions of furacilin (dilution 1:5000) and chlorohexidine (0.05%) against the nonspecific microflora and Mycobacteria tuberculosis allowed them to be used in the treatment of 55 patients with pleural empyema. Analyzing the outcomes of treatment in these patients versus 59 matched patients indicated that local ozone therapy accelerated sanitation and stimulation of reparative processes in this disease on the average by a fortnight. Local ozone therapy used in the preoperative preparation of patients with pulmonary tuberculosis and pleural empyema reduced the number of purulent postoperative complication to 17.7% versus 30.4% in the controls, enhanced the efficiency of multimodality treatment by 15.6% and reduced mortality by 9.5%. Analyzing the results of prevention of purulent bronchopleural complications after pleuropulmonectomy in 31 patients in the experimental group and in 35 in the control one showed that with local ozone therapy, complications occurred in 16.1 and 28.6%, respectively, and the efficiency of surgical management increased by 13.1% and mortality rates reduced by 9.6%. PMID- 11763555 TI - [Modern aspects of the combined treatment of pulmonary tuberculosis in adolescents]. AB - The paper presents the follow-up data on 171 adolescents with active pulmonary tuberculosis. Extensive, complicated processes were encountered in 30% of patients. Chemotherapy was used in relation to the severity of disease, to the presence of decay and bacterial isolation, to the sensitivity of Mycobacteria tuberculosis. Most patients received routine treatment regimens including four (n = 66) or three (n = 51) drugs. The treatment involved auxiliary drugs (tarivid, protionamid, amykacin). Pathogenetic treatments (lidase therapy, laser blood radiation, magnetic therapy) were employed. Comorbidity was also treated. Good results were achieved in 95.4% of patients. Hospital treatment decreased by 1.5-3 months. PMID- 11763556 TI - [Improvement of diagnostics and methods of determining effectiveness of chemotherapy against tuberculosis in children]. AB - Altered Mycobacterial forms, particularly granular forms, in the sputum and blood, as well as the serum level of tuberculosis antibodies and mycobacterial antigens by enzyme immunoassay are proposed to be determined as additional criteria for diagnosing active primary tuberculosis in children. The diagnostic value of these indices is accounted for by that they are more frequently detected and their levels are significantly higher than the similar ones in healthy, tuberculosis-infected children, and tuberculin-negative, earlier BCG vaccinated children. By taking into account a reduction in the detection rate of granular forms of Mycobacteria in the sputum and blood and altered levels of tuberculosis antibodies during chemotherapy, which were observed in parallel to the positive clinical and X-ray changes, these tests may be recommended for evaluation of the efficiency of treatment for primary abacillary tuberculosis in children. PMID- 11763557 TI - [Features of isoniazid activation in patients with tuberculosis and diabetes mellitus]. AB - Isoniazid inactivation was studied in 60 patients with concomitant diseases (pulmonary tuberculosis and diabetes mellitus). Thirty three patients had type 1 diabetes mellitus (Group 1) and 27 had type 2 (Group 2). Weak isoniazid inactivators were 81.2% in Group 1 and 51.9% (p < 0.02), which was much greater than those in patients with tuberculosis alone. The distinctive features of isoniazid metabolism in patients with diabetes mellitus were decreased acetylation of the drug and appropriate increased splitting and oxidation. In patients with type 1 diabetes mellitus, the prevalence of weak drug inactivation may both promote higher chemotherapeutical efficiency and enhance the likelihood of side effects. PMID- 11763558 TI - [Changes in lung function in patients with newly-diagnosed tuberculosis during treatment with short courses of controlled drug therapy]. AB - In 54 new cases of tuberculosis, VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, PaO2, PaCO2 were measured before, during, and after a short-term intensive controlled chemotherapy. Lung function improved in 57.4% of patients and deteriorated in 22.2%. There was a combination of better and worse lung function in 7.4%. The direction of functional changes depended on the form of tuberculosis, the extent of a tuberculous process, the duration and efficiency of chemotherapy. PMID- 11763559 TI - [Contribution of academicians from the Russian Academy of Medical Sciences named for A. G. Khomenko to physiatry and pulmonology]. PMID- 11763560 TI - [Radionuclide studies in physiatry and pulmonology: advances and prospects]. PMID- 11763561 TI - [Significance of hereditary factors in tuberculosis and other granulomatous lung diseases]. PMID- 11763562 TI - [Modern principles of treating bronchial obstruction in pulmonary tuberculosis patients]. AB - The efficiency of bronchodilating therapy described in the Federal Program for patients with chronic obstructive pulmonary diseases was evaluated in patients with lung tuberculosis with bronchial obstruction, treated in accordance with the Federal Program. Obvious advantages of modern inhalation therapy in comparison with the traditional methods were demonstrated: respiratory symptoms decreased and bronchial patency improved. These results recommend the therapy presented in the Federal Program for wide practical use. PMID- 11763563 TI - [New aspects of combined therapy of chronic pulmonary heart disease]. PMID- 11763564 TI - [Atypical and unfavorable variants in the course of sarcoidosis]. AB - Sarcoidosis with atypical clinical manifestations and a poor course accounts for 5.6% (78 individuals per 1400 patients). The paper describes the atypical manifestations of sarcoidosis (fever, hypereosinophilia, lymphocytosis, etc.) and its poor course, which are similar to those of lymphoproliferative diseases, fibrosing alveolitis-type sarcoidosis, infiltrative pneumonic forms). Each of the above manifestations has complex differentially diagnostic aspects. PMID- 11763565 TI - [Extracorporeal methods in treating sarcoidosis patients]. AB - The study was undertaken to develop basically new treatments of patients with sarcoidosis, namely: plasmapheresis and extracorporeal lymphocytic modification (ELM) with steroids, infrared laser or cytostatics. The authors analyzed the outcomes of treatment: 50 patients received plasmapheresis, in 52, 20, and 48 had ELM using prednisolone, infrared laser, and cyclosporin, respectively. Plasmapheresis used in the treatment regimen substantially reduced the dosage of corticosteroids. The outcomes of infrared laser therapy were comparable to those of plasmapheresis one. Positive clinical and X-ray changes of a tuberculous process were achieved with prednisolone or cyclosporin ELM in 95% of cases. As this took place, there were certain differences in the time course of X-ray changes. If prednisolone ELM promoted first of all reversal of interstitial changes, cyclosporin ELM affected a granulomatous process to a greater extent and alveolitis to a lesser one. Therapy-induced exacerbations were seen in none case. There were complications in 4% of cases. PMID- 11763566 TI - [Features of morphological reactions in caseous pneumonia]. AB - The morphological features of caseous pneumonia (CP) were studied in 90 patients aged 20-54 years by using specimens obtained at autopsy and surgery at the Central Research Institute of Therapy, Russian Academy of Medical Sciences and Moscow Clinical Tuberculosis Hospital No. 7. Thirty patients died from CP, 30 were operated on for CP. A matched group of 30 patients was operated on for fibrocavernous pulmonary tuberculosis (FCPT). Of the 30 patients operated on for CP, the process was classified as an individual nosological entity in 19 patients and as a complication due to FCPT in 11 patients. Out of the 30 deceased, CP was as an individual nosological entity in 17 patients and it complicated acute FCPT in 13 patients. Morphological (light and electron microscopy) and immunomorphological studies revealed the specific features of CP, which distinguished it from other forms of pulmonary tuberculosis. These included: the fulminant course and dissemination of lung tissue lesion, which is association with the appearance of intravascular blood coagulation and lung infarction; 2) development of immunodeficiency in the presence of autoallergy to the basilar membrane of lung vessels, macrophageal and lymphocytic dysfunctions; 3) extensive cell dystrophy of the air-blood barrier even in the intact portions of the lung; 4) hepatic dysfunction due to extensive dystrophy to the extent of hepatocytic micronecroses and dyscirculatory disorders. PMID- 11763567 TI - [Advances and perspectives in microbiological diagnosis of tuberculosis]. PMID- 11763568 TI - [Genotyping mycobacteria, isolated from incarcerated tuberculosis patients]. AB - The aim of the investigation was to genotype clinical Mycobacterium tuberculosis isolates circulating at the penitentiaries of the Ivanovo Region. Mycobacterial strains were genotyped by the polymorphism of the lengths of restrictive fragments containing the insertion sequence 6110 by the routine procedure. The genotypes of Mycobacterium strains were classified in accordance with the PHRI database (New York). The strains were characterized by their sensitivity to antituberculous drugs by the absolute concentration method. The investigations indicated that in terms of the IS6110 genotype there were prevalent Mycobacteria strains belonging to 2 families: a W family (62.5% of the strains) and an AI family (25%). In addition to the monocultures, genotyping also revealed 3 mixed cultures consisting of 2 strains. Determining the drug sensitivity of the genotyped strains demonstrated both drug-sensitive and drug-resistant strains, including multidrug resistance among the strains of the same genotyping family (W or AI). PMID- 11763569 TI - [Biochemical aspects of assessing reactivity of pulmonary tuberculosis patients]. PMID- 11763570 TI - [Genetic aspects of isolating risk groups for tuberculosis]. PMID- 11763571 TI - [Effectiveness of WHO strategies in prisons in the Ivanovsk district]. AB - The paper analyzes the results of implementation of the WHO recommendations on detection ad treatment of patients with tuberculosis in 1997-1999. A total of 8901 individuals with symptoms of suspected pulmonary tuberculosis were examined in this period. Sputum smear microscopy revealed acid-resistant bacteria (ARB) in 293 (3.3%) of the patients, including in 167 (57%) with their verification at clinical diagnostic laboratories of general health care units. A therapeutical success was achieved in 81.9% of the new cases of pulmonary tuberculosis who had ARB, in 85.7% of the patients without ARB, and in 72% with recurrent tuberculosis. PMID- 11763572 TI - Realistic program for teens discourages drunk driving. PMID- 11763573 TI - Recognizing and managing Website risks. PMID- 11763574 TI - Assessing medical error in health care. Controversy, challenge, and a culture of safety. PMID- 11763575 TI - A brief history. A summary of the development of the Ethical and Religious Directives for Catholic Health Care Services. PMID- 11763576 TI - Feeding tubes: sorting out the issues. Efficacy of artificial nutrition and hydration is determined by several clinical factors. PMID- 11763577 TI - Withdrawing nutrition and hydration. The Catholic tradition offers guidance for the treatment of patients in a persistent vegetative state. PMID- 11763578 TI - Filling gaps in the continuum. Fourth in a series examining revenue growth strategies in a difficult health care market. PMID- 11763579 TI - Long-term care financing. To achieve significant change, a functional national approach is needed. PMID- 11763580 TI - The view from AAHSA. Interview by Gordon Burnside. PMID- 11763581 TI - The prescription for long-term care. Improving the care of chronic conditions will have the single greatest effect on the long-term care crisis. PMID- 11763582 TI - A ministry of presence. Catholic health care in Memphis is anchored by a long term care center. PMID- 11763583 TI - Resident-centered care. Teresian House takes a team-based approach to care of the elderly. PMID- 11763584 TI - Agency-free at last! Leaders of a long-term care organization tell how they eliminated the need to hire temporary staff. PMID- 11763585 TI - The graying of America. PMID- 11763586 TI - Finding and keeping staff. The "employer of choice" strategy can give those who adopt it an advantage over competitors. PMID- 11763587 TI - Community networks. Youth recreation and self-esteem enhancement initiative. Little Falls, MN. PMID- 11763588 TI - Communities of practice. PMID- 11763589 TI - OIG work plan puts spotlight on discharge and transfer patterns. PMID- 11763590 TI - Formalize planning for continuum of care. PMID- 11763591 TI - ACI: update protocols or risk poor outcomes. PMID- 11763592 TI - Report gives 'benchmark' for ED disaster training. PMID- 11763593 TI - Clinicians must be voice of reason, reassurance now that bioterrorism battle has been joined. PMID- 11763594 TI - Should clinicians get smallpox vaccinations? PMID- 11763595 TI - Use of stents for small coronary arteries. Results of the Multi-Link 2.5 Portuguese Registry. AB - INTRODUCTION: Stents are being used with increasing frequency in percutaneous transluminal coronary angioplasty (PTCA) but their use in small vessels is still controversial, due to the possibility of excessively high rates of adverse events and restenosis. OBJECTIVE: To assess the safety and clinical efficacy of ACS RX Multi-Link (ML) 2.5 mm stents, in "de novo" coronary stenosis. DESIGN: Prospective Registry, with 6 months clinical follow-up, involving all Portuguese centers of Interventional Cardiology. POPULATION: Between April 7 and November 20 1998, 102 patients were enrolled, 82 male and with ages ranging from 30 to 86 years (average 58 +/- 11). Clinical presentation for PTCA was stable angina in 53%, unstable angina in 36% and silent ischemia in 11%. There was a history of previous myocardial infarction in 29% of patients. The main risk factors were hypertension (58%), hyperlipidemia (57%), smoking (25%) and diabetes (20%). Multivessel coronary artery disease was present in 46% of patients and left ventricular function was normal in 89%. Of the 217 existing lesions, 188 (87%) were treated: 35 with balloon angioplasty and 153 with stent implantation, 114 of which were ML 2.5 mm: 79 of 15 mm in length and 35 of 25 mm. METHODS: Angiographic success with ML stent implantation and major adverse cardiac events (MACE)--myocardial infarction (MI), coronary artery bypass graft (CABG), new target vessel revascularizations and death--were evaluated during hospital stay, and at 1 and 6 months clinical follow-up. RESULTS: Angiographic success was 97.4%. In one patient it was not possible to cross the lesion, in another there was stent migration and in a third distal coronary flow after stenting was TIMI grade 1. Clinical success was 96.1% and there were no cases of death, Q-wave MI or urgent CABG. Two patients had non-Q wave MI and two required urgent repeat angioplasty. Subacute stent thrombosis occurred in 1 patient. There were no additional MACE at 1 month follow-up. At 6-month follow-up (in 97% of patients) MACE had occurred in 14.1%: 2 deaths (one non-cardiac), 3 MI (one non-Q) and 14 new PTCA (one in a non-ML stent). There was no need for CABG in any patient. Six month survival rate was 97.9%, 94.9% were free of infarction and 84.8% were free of infarction and new revascularization. CONCLUSIONS: Multi-Link 2.5 mm stent implantation appears to be safe and efficient with a low incidence of immediate and 6-month adverse events in the range of centers and operators of the Registry. PMID- 11763596 TI - Results of the quantitative coronary angiographic analysis in the angiographic subgroup of the Multi-Link 2.5 Portuguese Registry. AB - INTRODUCTION: The restenosis rate of stents implanted into small coronary arteries is considered higher than that of stents in arteries > or = 3 mm, but could be influenced by clinical parameters and by the type and length of the stents. OBJECTIVE: To assess the incidence of angiographic restenosis at 6 months after implantation of 2.5 mm ACS RX Multi-Link (ML) stents, 15 and 25 mm length, in de novo coronary stenosis. DESIGN: Angiographic substudy of the Portuguese Multi-Link 2.5 Registry, which included Interventional Cardiology centers with facilities for coronary angiographic recordings allowing quantitative analysis. POPULATION: Between April 7 and November 20 1998 and in the 5 hospitals that agreed to participate, 61 patients were enrolled and 40 selected as having procedural and 6-month angiographies of sufficient quality for quantitative analysis. The only significant differences in the demographic, clinical and angiographic characteristics of the patients relative to those of the Registry were the lower prevalence of unstable angina and smoking in the angiographic substudy. There were 43 lesions and 46 ML stents were implanted. In 37% the lesions were located in the LAD, in 37% in the LCx and 26% in the RCA. 29 stents of 15 mm length and 17 stents of 25 mm were used. METHODS: The morphologic characteristics of the lesions were analyzed subjectively using the AHA/ACC classification. Quantitative coronary analysis (QCA) was performed, in an independent laboratory using the CAAS 2 system, for reference vessel diameter, lesion length, percentage of stenosis, minimum lumen diameter (MLD) and related parameters. Restenosis was defined as > or = 50% lumen obstruction at 6-month angiography. RESULTS: In the subjective analysis, 2 lesions were type B1, 27 type B2 and 14 type C. The overall restenosis rate was 32.6%. Restenosis was 27.7% for 15 mm stents and 36% for 25 mm stents (p = 0.4). For the QCA parameters analyzed, only MLD at the end of stent implantation was a predictor of 6-month restenosis (2.19 +/- 0.30 without vs. 2.03 +/- 0.18 with restenosis, p = 0.048). CONCLUSIONS: The restenosis rate of the Multi-Link 2.5 mm stents, of 15 and 25 mm length, was similar to that described with other types of stents in small coronary arteries. Minimum lumen diameter after stenting was found to be the best predictor of 6-month restenosis. PMID- 11763597 TI - Small is still beautiful. PMID- 11763598 TI - Ebstein's anomaly in neonates. AB - Ebstein's anomaly is a rare congenital heart disease abnormality in which the tricuspid valve leaflets do not attach normally to the tricuspid valve annulus. The effective tricuspid valve orifice is displaced apically into the right ventricle (RV), near the junction of the inlet and the trabecular parts of the RV. The authors present a retrospective study of the patients with Ebstein's anomaly admitted to a neonatal intensive care unit, in the period between January 1993 and March 2000. There were ten patients, representing 0.24% of total neonates and 1.99% of total congenital heart disease admitted to the institution in the same period. Fifty per cent were male and only one case had prenatal diagnosis. Holosystolic murmur (100%) from tricuspid regurgitation and cyanosis (80%) were the most frequent clinical findings. Chest X-ray was abnormal in 90% of the neonates, with a "balloon-shaped" enlarged heart. The main electrocardiographic findings were right atrial enlargement (70%) and arrhythmias (40%). Apical displacement of the septal leaflet of the tricuspid valve, to a maximum of 20 mm, and leaflets tethering to underlying RV myocardium were found in all patients. Tricuspid valve regurgitation was found in 90% (severe form in four cases). An atrial intracardiac shunt, mostly right-to-left, was also found in 50%. Digoxin was used (40%) to restore sinus rhythm. Fifty per cent of the neonates received intravenous prostaglandins. Two patients required a surgical procedure. Two patients died in the neonatal period. During the follow-up period (range 0.3-74.6 months), only one episode of supraventricular tachycardia was recorded. At present seven patients are clinically stable, three of them on medication. PMID- 11763599 TI - Neisseria meningitidis native valve endocarditis. A case report. AB - The so-called nonpathogenic neisseriae are common inhabitants of the upper respiratory tract in humans and are not usually regarded as pathogens. Neisseria meningitidis on the contrary may cause severe disease. These organisms are an uncommon cause of infective endocarditis. The authors report a case of a 64 year old male, type II diabetic, previously asymptomatic, admitted to hospital because of fever, aphasia and right hemi-paresis. A systolic murmur was heard at the cardiac apex, and three blood cultures were positive for Neisseria meningitidis. The echocardiogram showed a vegetation on the posterior leaflet of the mitral valve, allowing the diagnosis of meningococcal endocarditis. The patient's clinical condition improved on intravenous penicillin therapy, and regression of fever, disappearance of the neurological signs and of the mitral valve vegetation were observed. PMID- 11763600 TI - [Clinical pharmacology of the new antiarrhythmia agents]. AB - Antiarrhythmic drugs (ADs) are the mainstay in the treatment of cardiac arrhythmias. Arrhythmias merit treatment for the relief of symptoms and for the prolongation of survival for decreasing arrhythmic deaths. Since class I ADs can increase arrhythmia mortality in patients with coronary artery disease the interest has shifted to class III ADs, particularly those with greater effect at fast heart rates or with greater selectivity for atrial tissue. The recognition that some cardiac arrhythmias can be attributed to variable expression of specific genes or variability in the function of their protein products offers new perspectives for developing new ADs Moreover, the finding that heart disease alters electrophysiological properties of cardiac tissue suggests that we must target the arrhythmogenic substrate rather than its final electrical product. Advances in molecular genetics and electrophysiology will provide an opportunity to identify new targets and to design new ADs that are more effective and with lower risk of complications than those presently prescribed. PMID- 11763602 TI - [National Pacing Registry -- 1999]. PMID- 11763601 TI - [Cardiac effects of acute poisoning with tricyclic antidepressants: systematic review of the literature -- Part III]. AB - Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present this paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this third (of four) articles, the prognosis of tryciclic antidepressant overdose is presented (in the two previous articles--published in previous issues of the Revista--we discussed the epidemiological aspects as well as the clinical presentation and the diagnosis). In the remaining paper we will present its management, and prevention. Note: this is the third of a series of four articles on the cardiac toxicity of tricyclic antidepressant overdose; the final article will be presented in the October issue of the Revista. PMID- 11763603 TI - Endocarditis through infection of pacemaker probe visualized by transesophageal echocardiography. PMID- 11763604 TI - [Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization]. PMID- 11763605 TI - [DRG's: progress or a stumbling block? What is the meaning of the new case oriented cost-classification system for child- and adolescent psychiatry?]. PMID- 11763606 TI - [Mother-child interaction and externalizing disorders in elementary schoolchildren]. AB - OBJECTIVES: The behavior of eight-year-old children with externalizing disorders (ADHD and CD) in interaction with their mothers was examined. METHODS/RESULTS: Mothers of ADHD children were more restrictive and negative towards their children and showed less adequate control than did mothers of normal children. ADHD children paid less attention, were less assertive and helpless, and were more impulsive than controls. CD children were more negative towards their mothers, and were more aggressive and provocative than normal children, while their mothers were more impatient. CONCLUSIONS: An interaction between aggressive child behavior and maternal restrictiveness contributed to increased conduct problems. Hyperactivity was enhanced by the interaction between the impulsive behavior of the child and the aversive maternal response. PMID- 11763607 TI - [When should inpatient child and adolescent psychiatric treatment be terminated?]. AB - OBJECTIVES: As up to now no thorough empirical investigation of the length of stay during inpatient treatment exists, the criteria for the decision to terminate inpatient treatment were studied. METHODS: The opinions of experts in child psychiatry were collected by means of a three-part questionnaire that included a general section together with questions concerning the respective profession group of each expert, a structured section, and a section with open questions. 200 questionnaires were mailed to members of different professional groups at all hospitals for child and adolescent psychiatry in Lower Saxony and Bremen. 112 questionnaires were returned. Data were evaluated descriptively and by means of analyses of variance to determine whether the assessment patterns differ among the various groups. RESULTS: Complex criteria were found by attributing answers to both the structural and the open questions, which included patient-related aspects (particularly the course of symptoms and the child's/adolescent's development of competence), conditions in the family, administrative influences (aftercare and post-discharge placement), problems in the therapeutic setting, aspects of group dynamics between patients and staff, as well as problems involving motivation and compliance. The decision patterns in the professional groups did not differ. CONCLUSION: To reduce the length of inpatient treatment to criteria in accordance with DRGs would be to overlook essential professional aspects of a qualified decision process and thus constitute a misleading strategy with regard to effectiveness and efficiency. The use of the criteria found here as components of a quality management process might be a better way to achieve this goal. PMID- 11763608 TI - [Maternal stress among mothers of children with Williams-Beuren syndrome, Down's syndrome and mental retardation of non-syndromal etiology in comparison to mothers of non-disabled children]. AB - OBJECTIVES: This study assesses the quantity of stress in mothers of children with mental retardation of different etiologies (Williams Syndrome--WS, Down Syndrome--DS, mental retardation of different etiologies--MR) and in mothers of non-disabled children (MA). METHODS: 85 mothers were asked to complete the Parenting Stress Index (PSI) and the Child Behavior Checklist (CBCL). The groups were matched according to the children's age, sex, and verbal comprehension as assessed by the WISC-R. Data on the child's mental age (WISC-R) and the family's socio-economic level were collected. RESULTS: Significant differences were found in the Child Domain, but not in the Parent Domain of the PSI. According to the Child Domain, mothers of children with WS and DS scored significantly higher on the acceptance and demandingness scales, while mothers of children with MR scored higher on the acceptance scale than did mothers of children with MA. Moreover mothers of children with WS displayed the highest scores on the hyperactivity, mood and adaptability scales. Groups did not differ on the level of experienced reinforcement from their child. No significant differences were found in the Parent Domain according to the subscales attachment and social isolation. Mothers of children with DS scored higher than the other groups on the scales: depression, sense of competence and parent health. Mothers of children with MR scored lower on restriction of their role as a parent and relationship to their spouse. The degree of the children's mental retardation as well as conspicuous behavior correlated positively with maternal stress but not the familial socio economic level or the age of the children. CONCLUSIONS: Generally, mothers of children with mental retardation, regardless of its etiology, find it more difficult to accept their child than do mothers of non-disabled children. Specific behavior problems associated with the behavioral phenotype of a syndrome also influence the level of maternal stress. PMID- 11763609 TI - [Antisocial behavior in adolescence: risk factors and developmental types]. AB - Both the intensity and prevalence of violence and delinquency among children and adolescents have continued to rise during the past fifteen years. Efforts to counteract this development may benefit from recent evidence from developmental psychopathology and neurobiology. A model proposed by Moffitt describes two developmental pathways into antisocial problem behavior: one path characterized by an early onset and a stable course of symptoms ("life-course persistent") and the other by an episodic ("adolescence-limited") occurrence of anti-social behavior. While in the latter the specific developmental tasks and life circumstances of adolescence play a major role in the pathogenesis, persistent antisocial behavior is perceived to be a result of a transactional process between child and environment. Apart from psychosocial factors, biological predispositions (genetic susceptibility) and psychological dispositions (temperament and personality characteristics) are of primary interest. The recent progress in neurobiological and personality research promises significant insights into the underlying pathogenetic mechanisms. Integrating these approaches may help in targeting prevention and early intervention programs to high-risk groups and may thus contribute to improving their effectiveness. PMID- 11763611 TI - The evil face of terror. PMID- 11763610 TI - [Transcranial magnetic stimulation in child and adolescent psychiatry: excitability of the motor system in tic disorders and/or attention deficit hyperactivity disorders]. AB - Motor system excitability can be investigated in vivo by means of single and paired pulse transcranial magnetic stimulation (TMS). Whereas the cortical silent period reflects the general degree of inhibitory mechanisms mainly within the sensorimotor loop, intracortical excitability measures the focused degree of inhibitory and facilitatory mechanisms within the motor cortex. In child and adolescent psychiatric disorders with uncontrollable motor behavior such as tics in tic disorder or motoric hyperactivity in attention deficit hyperactivity disorder (ADHD), different dysfunctional patterns of motor system excitability could be demonstrated compared to age-matched healthy controls: (1) In tic disorder, a shortened cortical silent period was observed, providing evidence of deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. (2) In ADHD, a decreased intracortical inhibition was found, probably reflecting deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In order to investigate neurophysiological aspects of comorbidity, (3) motor system excitability was also measured in children with combined ADHD and tic disorder. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence of additive effects at the level of motor system excitability. These decreased inhibitory mechanisms within the entire sensorimotor loop and especially the motor cortex could be essential neurobiological substrates of the deficient inhibitory motor control and regulation, respectively, in tic disorder and ADHD. PMID- 11763612 TI - Reclaiming fees from patients. PMID- 11763613 TI - Suspected latex allergies. PMID- 11763614 TI - In vitro cytotoxicity of chlorhexidine gluconate, benzydamine-HCl and povidone iodine mouthrinses on human gingival fibroblasts. AB - Mouthrinses are frequently prescribed for the treatment of ulcerative diseases of the oral mucosa. In this study the in vitro cytotoxic effect of 0.2% chlorhexidine gluconate in water, 0.15% benzydamine-HCl in 8.5% ethanol and 1% povidone iodine in 10% ethanol were determined. Results of photographs and cell counts revealed that all the cells exposed to chlorhexidine gluconate, benzydamine-HCl and povidone iodine were immediately fixated onto the tissue culture surfaces. The three agents were then diluted in phosphate buffered saline to concentrations varying between 10% and 90% and fibroblasts were once again exposed to the dilutions of the test agents. Photographs were taken and cell concentrations in the wells were determined immediately after exposure and after 2, 4 and 24 hours. Results indicated that cells were immediately fixated by 10% chlorhexidine gluconate in water, 20% povidone iodine and 70% benzydamine-HCl. Fibroblasts survived and recovered from the exposure to 8.5% and 10% ethanol, which indicated that the fixation effect is not the result of the ethanol, but should be ascribed to the activity of the active ingredients in the mouthrinses. PMID- 11763615 TI - Trends in treatment performed in the Phelophepa Dental Clinic: 1995-2000. AB - Mobile clinics are a cost-effective method of meeting the dental needs of rural communities in South Africa. Phelophepa, the first primary health care train of its kind world-wide, provides eye care, education, medicine, basic health care and since June 1995 dental treatment to rural communities. All services are rendered by students under supervision of qualified staff. The aim of this study was to analyse and report the data for treatment performed in the dental clinic from June 1995 to May 2000. During its first five years of operation, dental services were provided at 183 towns in all provinces except Gauteng. Of the 42,073 patients treated during this time (an average of 229.9 per town), 67.4% were adults. 71.3% of the 103,283 procedures performed were extractions, 15.7% could be classified as preventive with the remaining 13% as restorative procedures. The average value of the service provided to each patient was R218.53. The exposure of dental, dental therapy and oral hygiene students to rural areas of South Africa serves the important purpose of sensitising students to the realities of oral diseases in these communities. PMID- 11763616 TI - Computer-assisted learning (CAL) in undergraduate clinical dentistry: a review. AB - OBJECTIVE: To review the effectiveness of computer-assisted learning (CAL) in undergraduate clinical dentistry. METHODS: A review of dental and related medical literature was conducted using a selective MEDLINE search and by manual search. RESULTS: An attempt was made to evaluate the results of computer-based teaching methods in clinical dentistry, and the future. Analysis of several controlled studies showed equivocal learning improvements for CAL when compared with other teaching methods in clinical dentistry. However, CAL technology and appreciation of the standards required for effective learning programmes have changed considerably since these early studies were published. CONCLUSIONS: There is considerable potential for effective computer-based education in undergraduate clinical dental programmes, and the Internet can provide better access to such material. However, using newer technologies, further controlled studies of the learning effectiveness and cost-effectiveness of CAL in clinical dentistry are required. PMID- 11763617 TI - Pre-authorisation: a purpose or a pain? PMID- 11763618 TI - [Sex-typical aspects of the physician-patient relationship of elderly patients in general practice]. AB - So far the issue of gender combination in the patient-doctor relationship has not been investigated in depth. In a cross sectional study 84 general practitioners of the Canton of Zurich were asked to give information on health problems and expectations of their patients over 55 years. Data regarding fears and expectations on the part of the physicians pertaining to their own age were assessed. Results show that cardio-circular, muscular-skeletal, fibre-tissue, urological, nutritional and metabolic system diseases as well as psychological and behavioural problems were most commonly diagnosed in older patients in general practice. Patients often had expectations not or difficult to fulfill by their physicians. Gender stereotypes appeared in the descriptions of typical older male or female patient. Female doctors characterise their patients similarly to their male colleagues. Regarding their own aging both genders reported fears of dependency. Female doctors primarily hoped for wisdom, whereas, their male colleagues wished for themselves health and more time for their own interests. Results indicate that the issue of gender combination and the competence in dealing with psychosocial problems of older patients should be given special consideration in graduate programs and continuous training of doctors. PMID- 11763619 TI - [General AL-amyloidosis: a rare complication in Waldenstrom macroglobulinemia]. AB - Waldenstrom's macroglobulinemia (W.M.) is a paraproteinemic disorder similar to multiple myeloma expressing a monoclonal IgM paraprotein. The course of W.M. is milder and the occurrence of renal disease is less frequent than in multiple myeloma. Amyloidosis occurs in less than 5% of patients with monoclonal IgM. We report a 65 year old patient with an asymptomatic long-term survival whose W.M. remained without any therapy. Amyloidosis developed twenty-one years after the initial diagnosis presenting with the nephrotic syndrome, renal and heart failure. W.M. combined with amyloidosis is a rare association. The deposition of amyloid causes progressive organ damage and indicates a bad prognosis. Most commonly nephrotic syndrome or heart failure are signs of amyloidosis. The development of amyloidosis does not seem to be influenced by the duration of W.M. disease or the paraprotein level. It is not known whether the amyloidosis can be prevented by an early chemotherapy. PMID- 11763620 TI - [The value of walking exercise in treatment of intermittent claudication]. AB - Physical training is one of the basic measures for all patients suffering from a generalized atherosclerosis. Specific training forms for PAD patients include home-based and structured, organized physical training programs; these are discussed and the results of meta-analyses presented. Whereas the published materials available for a home-based training is non-conclusive, structured training programs will lead to a statistically significant and clinically relevant improvement of a PAD patients' functional capacity. PMID- 11763621 TI - [Chlamydia pneumoniae: an cause of reactive arthritis?]. AB - Chlamydia pneumoniae is a common cause of acute infections within the upper respiratory tract. It is less well known that chlamydia pneumoniae, just like chlamydia trachomatis, may also trigger reactive arthritis. We describe three patients with arthritis possibly triggered by chlamydia pneumoniae. The patients showed the typical symptoms of reactive arthritis like asymmetric oligo- or polyarthritis, dactylitis, enthesiopathies and tendovaginitis. The course of the disease was quite different. The first patient developed persistent polyarthritis which required longterm treatment with a rheumatic disease modifying drug; the second patient improved after several weeks and the third patient experienced a full remission within a few days. PMID- 11763622 TI - [53-year-old patient with enlarged inguinal lymph nodes. Anal carcinoma]. PMID- 11763623 TI - [Endoscopy in endodontic surgery]. PMID- 11763624 TI - [Aspects of dental care of immunosuppressed patients. II. Organ transplantation]. PMID- 11763626 TI - [As carefully as in fire hazard. How to stop the methicillin resistant staphylococcus]. PMID- 11763625 TI - [Early growth and risk of coronary disease. Does it depend on fetal malnutrition, childhood conditions or genetic factors?]. PMID- 11763627 TI - [Proved association between low birth weight and coronary disease in adulthood. Too quick weight gain can disturb the muscle-fat balance]. PMID- 11763628 TI - [Control of methicillin resistant staphylococci at the Sahlgrenska hospital. Successful control program against MRSA outbreak]. AB - In 1998-1999 a strain of methicillin resistant Staphylococcus aureus (MRSA) infected 147 patients in 40 out of 160 ward units at Sahlgrenska University Hospital, Gothenburg. The strain originated from a patient who had been treated in a hospital in Cyprus. In order to control this outbreak a plan of action was decided upon and carried out, including extensive information to the hospital staff, screening for carriers, and establishing a hospital infection control committee. Furthermore, a policy for screening all patients readmitted to the hospital was established in November 1999. This screening could be discontinued on July 1, 2001. PMID- 11763629 TI - [Can asthma deaths in young people be predicted and prevented?]. AB - In spite of increased asthma prevalence, the mortality in the disease has decreased during the last two decades in Sweden and in some other countries. However, in the age group 15-24 years an increased death rate was noted at the end of the 1980s. Therefore we started a prospective study from 1994 with the aim of trying to analyse the precipitating factors of all deaths in the ages 1-34 years in which the death certificate alleged asthma or anaphylaxis as the main or contributing cause of death. We conducted a confidential telephone enquiry of the next of kin of the deceased using a modified questionnaire developed by the British Thoracic Association. When available, patient records and post mortem protocols were obtained. RESULTS: The mortality in asthma in the ages 1-34 years has decreased from around 5 per million/year to 0.5/million/year over the period 1987-1998. The main preventable factors found in this analysis are undertreatment, non-compliance, psychosocial factors including alcohol/drug abuse, food allergy and inhalation allergy. Lacking awareness of the risks and underestimation of the severity of the asthma both by the physician and the patient seem to be dominating factors. PMID- 11763630 TI - [Great geographic variations in the prevalence of asthma and allergy. International population studies to explain the associative factors]. AB - During the 1990's the international variation in the prevalence of asthma and allergy was studied in young adults (European Community Respiratory Health Survey, ECRHS) and in children (International Study of Asthma and Allergy in Children, ISAAC). The prevalence of asthma and allergy was highest in the United Kingdom, North America, Australia and New Zealand, lower in the Baltic countries and very low in some of the poorest republics of the former USSR. Children that lived in the countryside during the first year of life had a lower prevalence of atopic disease as teenager while in adults farmers had the highest prevalence of occupational asthma. In both investigations a negative association was found between having pets as a child and atopic sensitisation. This association could, however, be related to selection mechanisms. In a three year follow-up of the Swedish part of the ECRHS the incidence of asthma was higher in smokers than non smokers. Passive smoking was associated with respiratory symptoms in both children and adults. Follow-ups of both studies are being planned or performed. Further analyses of the geographic differences may explain the reason for the rapid increase of asthma and allergy in the Western world. PMID- 11763631 TI - [Peripheral and central nervous system stimulation in chronic therapy-resistant pain. Background, hypothetical mechanisms and clinical experiences]. AB - Severe neurogenic pain still constitutes a major problem since it is often resistant to conventional therapy. During the last 30 years electric activation of pain inhibitory mechanisms through stimulation both of peripheral nerves and of central nervous circuits has been used to great advantage. The simplest method of stimulation, transcutaneous electric nerve stimulation (TENS), is extensively used by physiotherapists as well as in pain clinics. The patient should always get his own stimulator for use at home. TENS originally served as a screening method to identify patients suitable for spinal cord stimulation therapy (SCS). The main indication is severe neuropathic pain of peripheral origin, but SCS has also been found valuable in extremity ischemia as well as in refractory angina pectoris. The most severe cases of neuropathic pain may benefit from intracranial stimulation via electrodes placed stereotactically in the posteromedial thalamus or epidurally over the motor cortex. PMID- 11763632 TI - [Children and bodily pain. Strong association between bodily pain, mental problems and sleep disorders among school children]. AB - Body pain is frequently reported in children, and it has been suggested that childhood pain could be the beginning of chronic disabling pain. Three hypotheses were tested: 1. Body pain is associated with mental distress and sleeping problems; 2. The association is dependent on the localisation of the pain; 3. The association increases with the number of painful areas. 86 percent of the pupils (569) in the 4th form (mean age 10.5 years), 7th form (mean age 13.5 years) and 9th form (mean age 15.5 years) from all the schools in a local community answered a questionnaire about self esteem, body image, physical activity and body pain. A strong association was found between the reporting of pain, mental distress and sleeping problems. Knee pain was the only problem reported more frequently by boys than by girls, and did not show the same association with mental distress and sleeping problems as pain from other regions. PMID- 11763633 TI - [Falsely increased creatine level--something to consider? Two cases with increased creatinine level without reduced renal function]. PMID- 11763634 TI - [Adverse effects of drugs in patients with heart disease lead to hospital care]. AB - Polypharmacy in patients with cardiovascular disease leads to an increased risk of developing adverse effects. At the Department of Internal Medicine at Stockholm Soder Hospital we studied computerized records and discovered that 14% of those hospitalized patients who were on drug treatment for cardiovascular diseases were admitted due to problems or symptoms possibly caused by their drugs. Interactions were less common; the symptoms which warranted hospitalization were more often caused by additive pharmacological effects. Obviously, adverse effects of drugs decrease quality of life, cause unnecessary suffering and treatment, and are expensive for the health care system. Screening of computerized records helps us detect adverse effects, and facilitates prevention. PMID- 11763635 TI - [Need for more research on female circumcision. Lack of communication between women and men conserves the traditional practice]. AB - Several studies in cultures in which FGM is widely performed have shown an emerging questioning of the value of performing the procedure, especially among the younger generations. Traditionally the practice has been said to be carried out by women in order to satisfy men. Recent research findings, however, indicate that men may have attitudes and preferences strikingly different from what has been ascribed to them in the literature. Thus men may play an important and positive role in future work to counteract the practice. Reinfibulation after delivery implies repeated genital mutilation. Despite this, reinfibulation has attracted little research, and not very much is known about the practice. There is a need for systematic research about the extent of complications of FGM, especially long-term effects including effects on pregnancy, delivery and the newborn child. Our experiences from research on FGM in Sudan indicate that research findings might be very useful in intervention programs. PMID- 11763636 TI - [Simple reference values and individual feedback are effective for quality work]. PMID- 11763637 TI - [Swedish occupational legislation in a historical perspective]. PMID- 11763638 TI - [Important progress presented at a European conference on meningococcal disease]. PMID- 11763639 TI - [The Swedish penicillin V model]. PMID- 11763640 TI - [Group dialogues with students during the 11th semester. Coordination of training of consultation skills is missing]. PMID- 11763641 TI - [The global health development--what is the status and what can be done?]. PMID- 11763642 TI - [Is the abolition of pulmonary artery catheterization use evidence-based?]. PMID- 11763643 TI - [Dangerous mother or a mother accused of being dangerous?]. PMID- 11763644 TI - [Publishing of scientific studies is no longer dependent on considerations of space in medical journals]. PMID- 11763645 TI - [Administration of analgesics is not participation in active euthanasia]. PMID- 11763646 TI - [What was the cause of Karl the XIIth death?]. PMID- 11763647 TI - The undiscovered Argentine pharmaceutical market. AB - The Argentine health care system is more highly developed than most systems in Latin America and gives most of its citizens access to a reasonable level of care. Now after 50 years of government control the system is becoming privatized, which provides new possibilities for health care marketers. One company developed an innovative approach to pharmaceutical marketing in Argentina that, while perhaps not appropriate for the U.S. market, may reap rewards in certain cultures and provide lessons for others. PMID- 11763648 TI - International market research at the Mayo Clinic. AB - Mayo Clinic has a long international history and has been providing care to international patients since its inception. Despite its history and reputation, however, the marketing staff continues to monitor the international market to gauge the level of awareness, reputation, and attractiveness of Mayo Clinic around the world. Here's a look at how one institution has used word-of-mouth marketing to maintain its global reputation. PMID- 11763649 TI - HIV services for a new generation. AB - Expanded treatment capabilities, supportive services, and education are available to control the AIDS epidemic as it spreads among new, harder-to-reach populations. Unfortunately, disparities in health status among these groups often prevent them from getting preventive care and treatment. To build awareness among today's at-risk population, health care marketers must address the needs of their target audience. With a well-planned and sensitive approach, they can work with practitioners to bring these services to the people who need them most. PMID- 11763650 TI - Marketing organ donation around the globe. AB - Marketing to potential organ donors in different countries requires knowledge about religious beliefs and cultural norms that might influence the decision to donate. Because beliefs vary so widely from country to country, marketers need to consider whether a standardized or adaptive approach is suitable for marketing organ donation in different countries. This article takes a look at the variables that influence the decision to donate an organ and suggests marketing strategies that may work in various parts of the world. PMID- 11763651 TI - Marketing alternative medicine. PMID- 11763652 TI - The changing face of health care consumers. AB - Caring for a diverse pool of patients is an ongoing challenge for health care practitioners and marketers. Communication difficulties and cultural misunderstandings still stand in the way and keep members of some minority populations from getting the health care they need. To better serve these groups, it's crucial to learn more about patients' values, needs, and expectations. Fortunately, opportunities abound for health care marketers to learn about and effectively target these still largely underserved populations. PMID- 11763653 TI - A neighborhood of nations. PMID- 11763654 TI - Marketing government-sponsored primary care services. PMID- 11763655 TI - Breaking down Internet barriers. PMID- 11763656 TI - The new childbearing family. PMID- 11763657 TI - Use teamwork to prepare for the unimaginable. PMID- 11763658 TI - Work plan outlines areas for compliance review. PMID- 11763659 TI - Trading in health: the World Trade Organization (WTO) and the international regulation of health and safety. PMID- 11763660 TI - Liability perspectives on reuse of single-use medical devices. PMID- 11763661 TI - The Personal Information Protection and Electronic Documents Act and the protection of personal health information. PMID- 11763662 TI - Nitric oxide and airway reactivity. AB - BACKGROUND: Nitric oxide is a neurotransmitter of the inhibitory nonadrenergic noncholinergic mediation in the respiratory system. Its participation in the regulation of airways functions is determined by its level in the organism. MAIN PURPOSE: We examined participation of nitric oxide in the changes of the airway reactivity evoked by toluene exposure as the source of the free radicals. The changes of nitric oxide level in the organism were evoked by administration of its indirect donor isosorbide dinitrate. Thiol groups were provided by administration of antioxidative mucolytic N-acetylcysteine. METHODS: Used drugs- isosorbide dinitrate (5 mg/kg b.w.) and N-acetylcysteine (300 mg/kg b.w.) were administered intraperitoneally or by inhalation 30 minutes before each exposure to the toluene vapours. The control group was not treated with drugs. After toluene exposure (2 hours in each of 3 consecutive days) tracheal and lung strips smooth muscle reactivity to histamine was observed under in "in vitro" conditions. RESULTS: The administration of isosorbide dinitrate decreased especially the lung strip smooth muscle reactivity to histamine. We revealed more expressive effect of the pretreatment with intraperitoneally administered isosorbide dinitrate in the comparison with inhalation. Simultaneous pretreatment with N-acetylcysteine intensified beneficial effect of isosorbide dinitrate probably by increasing of the intracellullary level of thiols. CONCLUSION: In our experimental conditions possible participation of nitric oxide in changes of airways smooth muscle reactivity after exposure to the toluene follows from results, as well as the importance of thiol groups for the activity of its indirect donors. (Fig. 6, Tab. 3, Ref. 35.) PMID- 11763663 TI - Serotonin and 5-hydroxyindole-acetic acid. AB - BACKGROUND: In patients suffering from chronic renal insufficiency (CRI) serotonin (5HT) metabolism is impaired, and plasma 5-hydroxyindoleacetic acid (5HIAA) levels (main metabolite of 5HT) are increased. AIM: In this study we aimed to give a detailed description of peripheral serotonin metabolism in healthy subjects and patients with CRI, and to evaluate the efficacy of hemodialysis in the elimination of cumulated 5HT and 5HIAA. METHODS: 5HT (platelet rich plasma, platelet poor plasma, urine, HPLC with electrochemical detection) and 5HIAA (plasma, urine, HPCL with electrochemical detection) levels were evaluated in 14 conservatively treated (CT) and 12 hemodialysed (HD) patients with CRI and were compared to those of 60 healthy volunteers (HV). RESULTS: In patients with CRI accumulation of 5HT and 5HIAA in plasma with no changes in platelet 5HT content was revealed. 5HT renal and fractional excretion (FE) was markedly decreased in CRI. FE-5HT was < 1 in all investigated subjects, indicating its reabsorption in proximal tubules, or local degradation to 5HIAA. Due to the increased filtration load renal excretion of 5HIAA was not altered in CT patients, however it was decreased in HD patients. The relative participation of glomerular filtration in 5HIAA renal excretion increased in CRI. FE-5HIAA > 5 was found in 20% of HV and 15% of CT, pointing indirectly to 5HIAA intrarenal production. In CRI FE-5HIAA decreased. HD did not eliminate accumulated 5HT and 5HIAA effectively. CONCLUSION: Increased levels of 5HT and 5HIAA might exert metabolic effects contributing to the clinically manifested impairments characteristic for uremic syndrome. (Tab. 3, Fig. 3, Ref. 27.) PMID- 11763664 TI - Late effects of anticancer therapy on kidney function in children with acute lymphoblastic leukemia. AB - THE CURRENT STATE: Children with curable cancer are potentially at risk of long term renal sequelae. The nephrotoxicity is considered dose related and includes a variable reduction of glomerular filtration rate along with tubular dysfunction. SUBJECTIVE: The aims of the present study were: to analyse kidney damage as well as the clinical course in children treated for ALL, to determine what type of nephrotoxic damage is most frequent in relation with the used treatment, to determine possible risks of acute and chronic nephropathy of anticancer therapy, to standardise evaluation of kidney function in children after their complex antitumourous treatment has finished. METHODS AND MATERIAL: We examined a group of 36 children (21 boys, 15 girls, average age at diagnosis of ALL 6.9 years)) treated for ALL using the therapeutical protocol ALL BFM 90. The average period after the treatment had finished was 48 month. The following parameters were examined: urinalysis and urine sediment, clearance of creatinine, tubular resorption, ultrasound of kidneys, 24 hrs proteinuria (PU) and urine concentration of albumine, transferine, alpha-1-microglobuline and Tamm-Horsfall protein. Concentration function of kidneys was examined by test with DDAPV. RESULTS: After finish of cytostatic therapy had 19 patients (52.8%) PU. Glomerular PU was found in 3 children (15.8%), in 3 children (15.8%) was found mixed PU and 13 children (68.4%) had tubular PU. Reduction of GFR had 5 patients (13.9%) and 19 patients (52.8%) had reduction of DDAPV test. CONCLUSION: Sensitive laboratory analysis of proteinuria is required for timely detection of the most frequent type of kidney damage in the course of treatment with cytostatics but also other concurrently administered drugs. Thus we can reliably detect mainly patients with glomerular/mixed proteinuria who are potentially imperilled by the risk of the development of chronic renal failure. If there is higher level of glomerular/mixed proteinuria even after the treatment has finished, the patients have to undergo another nephrological monitoring. (Tab. 3, Ref. 20.) PMID- 11763665 TI - Surgical treatment of injuries of nervus fibularis. AB - STARTING POINT: In this retrospective study, we present the results of 40 surgeries of 40 patients that within the period of 15 years, i.e. from 1985 to 1999 were provided the treatment of 40 lesions of n. fibularis, historically treated as problematic in terms of successful healing. The work provides the fundamental lines of their surgery treatment. MATERIAL AND METHODS: From the total number of 40, external neurolysis was performed to 20 patients. The remaining 20 patients were provided with reconstruction surgeries of the injured nerves, while 8 surgeries was done by suture of peripheral nerve and 12 surgeries were performed by nerve graft, in cases of complete and persisting neurological deficit and absence of action potential at EMG. The mechanism of lesion included the damages of nerve from elongation, with or without fracture, "sharp" or "blunt" lesions, lesions of shooting, compressions and iatrogenic injuries. If the spontaneous adjustment did not occur within the period of 2-6 months after the lesion, the patients underwent surgery. We performed the analysis of the efficiency of the surgical intervention depending on the following parameters: period of surgery from the lesion, patient's age, nature of lesion, degree of lesion, type of surgery intervention. RESULTS: With 27 of 40 an effective adjustment was achieved preventing the sagging of the foot trace and with 25 of 40 protective sensitivity appeared. After neurolysis with 18 of 20 patients (90%) we achieved effective degree of adjustment in spite of heavy pre-surgical motor deficit. With 8 patients an "end to end" suture was performed and with 6 (75%) the degree of adjustment was 3 or higher. 12 patients requested reconstruction surgeries with the help of nerve grafts, the length of grafts varied from 4 to 20 cm. The grafts were shorter than 5 cm with 2 patients, 1 with cut lesion and 1 patient with iatrogenic lesion. With both patients the function was adjusted to the degree M4. With 1 of 4 patients (25%) with the graft of 6 to 12 cm and with none of 6 with the grafts from 13 to 20 cm the adjustment of the degree 3 or higher was not achieved. In this cases, however, we noticed partial adjustment of trophic and tonus, however at the absence of motor adjustment. CONCLUSION: The pre-surgical and persurgical examinations are indispensable conditions for obtaining optimal results. It is worth of mentioning that surgical treatment proximal lesins of n. fibularis yielded better results than treatment of more distal lesions in the area of knee. (Tab. 5, Ref. 20.) PMID- 11763666 TI - Benefits of beta-blockers in heart failure. AB - The problem of heart failure (HF) has become a topic of great interest. Until recently, the use of beta-blockers in patients with HF was considered as a contraindication. Times have changed and the contraindicated drug is now an advised and preferred one to be used in HF patients with certain advised recommendations for its use in a safe and beneficial way. Still we need to emphasize the benefits of these agents in order to achieve more application in HF patients. Here we try to stress the proved beneficial effects of beta-blockers by major studies in HF patients, and to supply the reader with practical information regarding the use of these agents with a look at the frequency of using them and the possible reasons behind their underuse. The files of heart failure patients admitted to 1st Internal Department in the University Hospital in Bratislava in the period between January and December 1997 were checked to show the magnitude of using beta-blockers in them. Among 150 patients admitted during the above mentioned period only 30 patients (20%) received beta-blockers. It seems that beta-blockers have to be used in all patients with HF with reduced ejection fraction unless a real contraindication exists, but the actual data shows that beta-blockers are still underused. (Tab. 2, Ref. 30.) PMID- 11763667 TI - New approach to evaluation of clinical state in patients with multiple sclerosis. AB - The authors used a new method of evaluating clinical disability--Multiple Sclerosis Functional Composite (MSFC). Three quantitative tests, for the upper, lower extremities and cognitive functions, were used in 90 multiple sclerosis (MS) patients. The correlation between these results and Expanded Disability Status (EDSS) has shown that in slightly disabled patients there was achieved relatively high correlation especially for the upper extremities function. Their function remains saved for comparatively a long time. During the gradual deterioration of clinical status high correlation between the severity of disability and lower extremities function was achieved. The lowest degree of correlation was observed in cognitive functions, which are monitored more senzitively by MSFC method than by EDSS. The best correlation was revealed in seriously disabled group, not in slight and moderate affections, because EDSS evaluates these functions only marginally and cannot catch discover the beginning of the cognitive deficit. (Tab. 1, Ref. 4.) PMID- 11763668 TI - Atypical course of the median nerve. AB - Work in the form of anatomical casuistry is presenting and describing the atypical course of the median nerve found in both upper limbs of one of the cadavers in the Department of Anatomy of Medical Faculty of Comenius University in Bratislava. This atypical course was found during the students' dissection of the peripheral nerves and vessels. This non-standard course of the median nerve is compared with standard course described in anatomical literature and atlases, and confronted with the possible variations of the median nerve and its course described by the available literature. (Fig. 4, Ref. 4.) PMID- 11763669 TI - Eradicative effect of cotrimoxazole and quinolones on non-typhoid salmonellae. AB - Opinions on antibiotic treatment of salmonella gastroenteritis are still different. Many authors support an opinion that antimicrobial treatment has no effect on salmonella elimination. The authors of the study have tried to prove that fluoroquinolones shorten the elimination of salmonellae and therefore they are useful not only for the treatment of salmonella gastroenteritis in immunocompromised patients to prevent sepsis and extraintestinal manifestations of the infection, but also for eradication of salmonellae in food industry workers, whose carrier state might exclude them from their work. (Tab. 3, Ref. 10.) PMID- 11763670 TI - Report of first experience with endoscopic ultrasonography in Slovak Republic. AB - BACKGROUND: Endoscopic ultrasonography (EUS) is a method that takes the advantage of a combination of endoscopy and ultrasound, where a miniature probe that functions as a transducer (which functions as both a transmitter and a receiver of ultrasound), is incorporated in the tip of the endoscope. From the introduction, this modality has found it s uninterchangable place all over the world not only in the diagnosis, but also in the therapy of gastrointestinal diseases and the diseases of the surrounded structures and organs. Indications for EUS can be simply divided into three main categories: submucosal abnormalities, staging of tumors of the gastrointestinal tract and pancreatobiliary diseases. In December 2000 we began at the Clinic of Gastroenterology of Slovak Postgraduate Academy of Medicine at St. Cyril and Method s Hospital in Bratislava, Slovak Republic with the EUS evaluation with radial mechanical probe, as the first one in the Slovak Republic. In this article we describe our first experience with the EUS at our clinic. CONCLUSIONS: All together 64 patients were evaluated from December 2000 to the end of March 2001 from all over the Slovakia. In this article we describe in more detailed form the indications and also the findings in our group of patients. PMID- 11763671 TI - Medical physics education from the view of the possible structural changes. AB - Teaching subject physics at the university level represents a specific didactic transformation of the scientific field--physics. The determination of the content, extent, used methods, mutual relation to other subjects of curriculum as well as to the entrance knowledge of students are the most important parts of pedagogical activities in the educational process. Based on own experiences, successes and mistakes in teaching so-called medical physics the authors discuss didactic procedures which should support the interest and creativity of students. Some changes in the structure of physics education are recommended. The usefulness of the international collaboration in the framework of projects such as TEMPUS, ERASMUS is also remembered. PMID- 11763672 TI - Locus DR in primary Sjogren's syndrome. AB - The primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy which is presenting with progressive dryness of the eyes and the mouth, changes in the parotid glands and not rarely with systemic (extraglandular) manifestations. The development of the immunogenetics proved that the course of the disease is genetically determined. HLA-antigens, associated with pSS differ in the separate races, populations and ethnic groups. PMID- 11763673 TI - Radiofrequency catheter ablation of common-type atrial flutter guided by conventional versus electroanatomical mapping. AB - Radiofrequency catheter (RF) ablation aiming the complete conduction block of the cavotricuspid isthmus has become treatment of choice for common type atrial flutter. Different approaches to guide the ablation procedure are used. For the conventional approach multipolar catheters in the right atrium and in the coronary sinus are required to detect the induction of conduction block via the isthmus. RF current is applied starting at the ventricular site of the cavotricuspid isthmus under fluoroscopic control to recognise dislocation of the ablation catheter and to avoid potential complications. Three-dimensional electroanatomic (CARTO) activation mapping can be helpful to guide atrial flutter ablation. By the help of a magnetic sensor, embedded in the tip of the mapping catheter, a virtual frame of the cavotricuspid isthmus will be reconstructed. The middle region between the virtual septal and posterolateral border of the cavotricuspid isthmus will be targeted for the ablation lesion line. Both approaches have been shown to be associated with a high acute success rate and a low recurrence rate. The major difference is that the CARTO system leads to a substantial reduction of fluoroscopic time required for atrial flutter ablation. Thus, CARTO-guided ablation directed at the cavotricuspid isthmus represent a modern method for rapid and successful treatment of common-type atrial flutter with low radiation exposure. (Fig. 4, Ref. 16.) PMID- 11763674 TI - Endocrine activation in tachycardias. AB - This article reviews the complex character of neuroendocrine response to paroxysmal tachycardia. While the endocrine influences in arrhythmogenesis are well perceived by the cardiologists, less attention has been paid to influence of tachycardia on neuroendocrine activation. However, this may significantly alter the clinical course of tachycardias and its responses to pharmacotherapeutic interventions. Main characteristics of hormones with direct relationship to cardiovascular system (ANP, AVP, catecholamines, angiotensin and others) are listed with description of regulation of their secretion and main biological effects, especially with regard to regulation of circulation. Changes in hemodynamics during tachycardia with accompanying changes in ANP, AVP renin angiotensin-aldosterone system, sympatho-neural and sympatho-adrenal activation are reviewed. Further research and understanding require more complex approach and concentration on interrelationship of different regulatory hormones in tachycardia. (Fig. 2, Ref. 96.) PMID- 11763675 TI - The internal mammary artery bypass--the principles of preoperative and postoperative diagnosis using colour-duplex ultrasound. AB - BACKGROUND: The aim of the study was the assessment of functional characteristics of the left internal mammary artery (LIMA) bypass in patients after coronary artery bypass grafting (CABG) in comparison with the native LIMA using colour duplex ultrasound as the non-invasive diagnostic method. METHODS: We examined 303 patients after myocardial revascularization with the internal mammary artery bypass using the Hewllett Packard 2500, 5500 ultrasound units. Using the 7.5 MHz linear transducer we detected the LIMA from the left supraclavicular approach. We assessed the peak systolic velocity (PSV--cm/s), peak diastolic velocity (PDV- cm/s), end-diastolic velocity (EDV--cm/s) and we calculated the peak systolic/peak diastolic velocity ratio (SDVR) and resistance index RI (PSV EDV/PSV). The obtained parameters were compared with the native LIMA flow characteristics of the 70 consecutive patients before CABG. RESULTS: We observed the transformation of internal mammary artery flow from the predominantly systolic high resistance type of the native LIMA, to the low resistance biphasic waveform after its use as a coronary artery graft. We detected a significant increase of diastolic flow velocities and a significant decrease of resistance and of the SDVR ratio. In dysfunctional grafts we found a decrease of diastolic flow and an increase of LIMA resistance and SDVR. CONCLUSION: The colour-duplex ultrasound is a perspective non-invasive method for the postoperative follow-up of patients with the LIMA graft. It allows the assessment of the bypass flow characteristics, functional status and patency and it could contribute to the early diagnosis of bypass failure. (Fig. 6, Tab. 4, Ref. 21.) PMID- 11763676 TI - The role of the initial 12-lead ECG in risk stratification of patients with acute coronary syndrome. AB - This article reviews the prognostic significance of the initial 12 lead ECG in acute coronary syndrome (ACS). In patients with non ST segment elevation ACS, the initial ECG may vary from a normal one to an ECG which demonstrates T wave inversion and ST segment deviation. Patients, who present with either a normal ECG or T wave inversion in less than 5 leads, are considered to be at low risk. Those patients who have ST segment depression or a combination of ST segment depression and elevation have the highest incidence of cardiac death, re infarction and recurrent chest pain. In patients with ST segment elevation ACS, the mortality and morbidity is mostly influenced by infarct size. The ECG findings which correlate with infarct size are 1) the degree and extent of ST segment elevation, 2) the infarct related coronary artery and 3) distortion of the terminal portion of the QRS complex. Patients with acute anterior wall myocardial infarction due to a proximal occlusion of the left anterior descending (LAD) coronary artery have the worst short and long-term prognosis. The ECG manifestation of a proximal left anterior descending artery occlusion is ST segment elevation in lead aVL and the precordial leads, combined with ST segment depression in the inferior leads. With regard to patients who have an acute inferior wall myocardial infarction, the patients at highest risk are those with a proximal right coronary artery (RCA) occlusion artery and posterolateral extension. The ECG findings in proximal right coronary artery occlusion are ST segment in the inferior leads and in V4R. Less frequently ST segment elevations may be present in lead V1 and V2. Patients with posterolateral wall extension can be identified by the presence of ST segment depression in the right precordial leads. Finally, distortion of the terminal portion of the QRS complex is an important indicator of poor outcome. (Fig. 3, Ref. 42.) PMID- 11763677 TI - Quantitative characterization of the relief of body surface potential distribution. AB - The body surface distribution of the cardiac electric field is best represented as reliefs of positive and negative potentials, or their time integrals. The objective of this study was to design a methodology of their quantitative evaluation. QRST isointegral maps were obtained from 45 healthy subjects (35 men, 10 women, aged 10-67 years) using a 80 electrode set. Relative frequencies of positivity and of negativity were ascertained for different levels of the QRST integral values. Two fuzzy subsets: that of positive and that of negative QRST values were defined on the set of electrode placements. The values of membership functions of their elements were derived from relative frequencies obtained in the reference group of subjects, separately for all levels of QRST integral values. Statistics of these values characterize the reference reliefs of the positive and of the negative QRST values and are used to test their resemblance to a given individual distribution. In conclusion, the representation of isopotential, or isointegral body surface potential maps as reliefs of their positive and negative values, based on the theory of fuzzy sets, enables a quantitative evaluation of their resemblance to a given individual distribution. (Fig. 6, Ref. 18.) PMID- 11763678 TI - Prolactin and interleukin 2 concentrations before and after i.v. TRH application in primary hypothyroidism and in controls. AB - The authors evaluated serum level of prolactin (PRL) and interleukin 2 (IL-2) before and after i.v. application of tyreoliberin (TRH) 0.2 mg in 10 women as controls and 10 women with primary hypothyreoidism. In controls, there was a significant increase of IL-2 20 min following application of TRH (IL-2 0 min: 17.95 +/- 11.69, IL-2 in 20 min: 33.36 +/- 17.73 fmol/l), in patients with hypothyreoidism the serum level of IL-2 decreased (IL-2 0 min: 31.32 +/- 19.0, IL 2 in 20 min: 19.11 +/- 17.8 fmol/l). The basal concentration of IL-2 in patients with hypothyreoidism was significantly higher as in controls (p < 0.01). The presented finding indicated relation between the neuroendocrine and immune system but its value is not yet apparent. (Tab. 4, Fig. 1, Ref. 7.) PMID- 11763679 TI - Stress and health-related behaviour, personality characteristics and blood pressure in older school children. AB - BACKGROUND: Frequent stress contributes to physical and psychical disorders already in school-age children. Subjective evaluation of stress level is considered adequately informative for differentiating eustress and distress. OBJECTIVES: Assessment of the extent of stress and connections with health related factors and characteristics is a precondition for health promotion and stress prevention in school children. METHODS: In a cross-sectional study we analysed data from 213 older school children (107 boys and 106 girls) aged 10 and 14 years. Use was made of a self-evaluation questionnaire to assess the stress level, behavioural factors, feeling of health, 7-day report of data on diet and physical activity, J.E.P.I. test (Eysenck, 1971) evaluating neuroticism and extroversion. Sport activities were expressed as FIT value (product of frequency, intensity and time of exercises) and daily energy balance as ratio of average daily energy intake and energy expenditure. RESULTS: The girls felt stress more frequently than boys (38.7% vs 24.3%, p < 0.03). School stress was significantly more frequent than home stress. The stressed students more negatively evaluated their health and physical performance. The relation between stress degree and neuroticism score was confirmed. Sport and physical activities were significantly lower in boys with high stress load. Any closer relations between frequency of stress and health risk behaviour, sleep as well as school performance and blood pressure failed to be confirmed. CONCLUSION: The results have indicated the need of lowering school stress. One of effective ways is to promote physical activity in the life of children. (Tab. 3, Fig. 1, Ref. 24.) PMID- 11763680 TI - Special character of atrial paroxysmal fibrillation in coincidence with WPW syndrome. AB - The paper summarizes the knowledge on paroxysmal atrial fibrillation in WPW syndrome. The peculiarities, ECG features, risk markers of sudden cardiac death, pharmacologic and non farmacologic therapy and prevention of this arrhythmia are presented. Potentially dangerous effects of drugs such as digoxin, verapamil, adenosine and betablockers are emphasized. PMID- 11763681 TI - Metabolic cause of Reye-like syndrome. AB - The most frequent metabolic cause of Reye-like syndrome is medium chain acyl-CoA dehydrogenase (MCAD) deficiency. The authors describe a gypsy boy who was repeatedly hospitalised due to symptoms of Reye-like syndrome (serious hypoglycemia, loss of consciousness, seizures, increased values of aminotransferases, decreased values of free carnitine). The diagnosis of MCAD deficiency was established by analysis of plasmatic acylcarnitines by use of tandem mass spectrometry. DNA analysis proved the most common K329E (G985) mutation in gene for MCAD deficiency in homozygous state. The authors have emphasised the advantage of tandem mass spectrometry in the diagnosis of disorders of fatty acid beta-oxidation. This highly sophisticated method can detect most of these disorders from dry blood spots disregarding the symptoms and type of mutation. PMID- 11763682 TI - Importance of echocardiography in atrial fibrillation. AB - Echocardiography influences at present in decisive manner therapeutic approach to atrial fibrillation (AF). The paper discusses current knowledge regarding the role of echocardiography in routine management of cardioversion for AF and regarding the echocardiographic prediction of: 1. the thromboembolism in AF, 2. the efficiency of cardioversion for AF, 3. the maintenance of sinus rhythm after successful cardioversion for AF. The advantage of TEE-guided cardioversion is particularly emphasized. PMID- 11763683 TI - Specialities of assessment of endurance capabilities in sport active children. AB - Maximal oxygen uptake (VO2 max) belongs to most important functional parameters of physical fitness testing and consideration of endurance capabilities. The value of VO2 max depends on age, gender, genetic disposition, body dimensions and physical fitness. Spiroergometric examination was done on cycle ergometer (ramp 25-35 W per minute) at vita maxima. One hundred and seventy children (129 boys and 41 girls) at the age of 8 to 17 were examined. The obtained results showed that absolute values of maximal oxygen uptake progressively rise during the course of childhood and gender differences between boys and girls started at the age 12-13 years. PMID- 11763684 TI - Brain embolism, left atrial thrombi and cardiosurgery. AB - Patients with embolization into the brain and mobile thrombus in the left atrium (LA) are in the danger of recurrent embolization. A patient with the history of recent cerebral vascular accident (CVA) would be at higher risk of cerebral complications due to cardiopulmonary bypass and this risk may be as high as that of re-embolization. We present a case of a 41-year old man with an acute ischemic focus (3 x 3 cm) in the temporoparietal lobe verified by computer tomography (CT). Transthoracic echocardiography showed severe aortic insufficiency, low ejection fraction of dilatated left ventricle (LV). Transesophageal echocardiography showed a mobile thrombus (2.2 x 1.1 cm) in LA. The cardiovascular surgeon consultant did not recommend urgent operation. Instead, the patient was treated by low molecular heparin. CT of the brain after 10 days of treatment was normal. Patient underwent a successful aortic valve replacement. At the time of surgery there was no thrombus in the LA. Subsequently, the patient recovered normally with no neurologic sequelae. This case illustrates the difficulty arising from the consideration of the relative risks of acute surgery vs conservative management in patient with recent CVA and a large mobile thrombus in LA. PMID- 11763685 TI - Undergraduate medical education in Slovakia--present state and future needs. AB - There is a lot of problems related to undergraduate medical education (UME) at Slovak medical schools, e.g. low level co-ordination and integration of curriculum, isolation of teaching subjects, amateurish teaching methods, low level of management, which result in low level of effectivity, late and insufficient reactions to the needs of medical practice. There is urgent need for complex reform of UME if we like to be able to complete with high quality medical schools in Europe. The reform should be focused to the content of curriculum--to integrate preventive and acute medicine into the UME, to improve training of medical students for service in primary health care, to start with renaissance of humanistic education of medical students, to improve research training and teaching of medical informatics. For improving organisation of UME it is necessary to prepare modern profile of graduates from medical school, and from the profile to derive co-ordinated and integrated system of UME. The teachers at medical school should be professionals not only in medical specialization, but in pedagogy, psychology and management, too. Passive forms of education (e.g. lectures) should be partly substituted by active methods, e.g. problem--based learning. More attention should be devoted to elaboration of criteria for evaluation quality of teaching process. The reform of UME have to be done if we like to have a chance to be as good as the best medical schools in Europe. I believe, we want it all! (Ref. 31.) PMID- 11763686 TI - [The quality of care of femoral fractures secondary to occupational accidents cannot be inferred only from third level medical care]. PMID- 11763687 TI - Iron deficiency anemia in Tarahumara women of reproductive-age in northern Mexico. AB - OBJECTIVE: To determine the prevalence of iron deficiency anemia (IDA) among Tarahumara women of reproductive age. MATERIAL AND METHODS: A cross-sectional survey was conducted in a representative sample of 481 women aged 12-49 years, residents of Guachochi Municipality, Chihuahua, from June to September 1998. The hemoglobin (Hb) level was measured in capillary blood using the Hemocue technique, and the serum ferritin level in capillary serum spotted on filter paper, in a sub-sample of women. Central tendency and dispersion measures were estimated; the Chi-squared test was used to test differences in proportions and ANOVA and Bonferroni's test for differences in means. RESULTS: Prevalence of anemia (mean Hb +/- S.D.) was 16.1% (140 +/- 16 g/l) and 25.7% (129 +/- 12 g/l) for non-pregnant and pregnant women, respectively. Pregnant women in the 3rd trimester and those who were breast-feeding their children during the first 6 months after delivery had the highest prevalence of anemia (38.5% and 42.9%, respectively). Iron deficiency was responsible for most of the anemia found in this sample. CONCLUSIONS: This study provides relevant information for the development of intervention programs to treat and prevent IDA in this ethnic group. PMID- 11763688 TI - [Relationship between maternal and neonatal iron stores]. AB - OBJECTIVE: To establish the relationship of normal, low, and moderate blood iron values in mothers and their newborns. MATERIAL AND METHODS: A cross-sectional study was conducted among 163 pregnant women and their newborns, users of Hospital de Ginecologia y Obstetricia numero 15, Instituto Mexicano del Seguro Social, from Chihuahua, Mexico. The mothers' clinical histories were collected and analyzed; hemoglobin, hematocrit, and ferritin serum levels were measured in maternal and umbilical cord samples. Iron maternal stores were determined by ferritin (microgram/l) values as follows: low: < or = 11; moderate: 12-20; and normal: > or = 20.1. The Kruskal-Wallis test was used to establish differences among group; the chi-squared test to determine differences of proportions; and Pearson's correlation coefficient for assessing the association between maternal and newborn iron stores. RESULTS: A weak correlation between maternal and neonatal ferritin was found (r = 0.14, p = 0.07). Geometric means of neonatal ferritin for low, moderate, and normal maternal iron stores were 4.77, 4.85, and 5.02 respectively (p = 0.12). The maternal iron stores changed after iron supplementation (p = 0.01). CONCLUSIONS: Iron stores in mothers and their newborns are closely related. Women who take iron supplements during pregnancy have significantly higher iron stores at the end of pregnancy. PMID- 11763689 TI - The prevalence and treatment of hypertension in the elderly population of the Mexican Institute of Social Security. AB - OBJECTIVE: To assess the prevalence and treatment of high blood pressure among elderly people in Mexico. MATERIAL AND METHODS: A cross-sectional study was conducted from February to July 1998 among the elderly people covered by the Instituto Mexicano del Seguro Social (IMSS) healthcare services in Mexico City. The study population consisted of 4,777 subjects aged 60 years and over, selected from a cohort of 5,433 people, representative of the population of Mexico City. Trained nurses carried out three blood pressure measurements at home. Diagnosis of high blood pressure was established if systolic pressure was equal to or higher than 160 mmHg, and/or diastolic pressure was equal or higher than 90 mmHg, or by self-report of a medical diagnosis of hypertension. Demographic and risk factor information was also collected. RESULTS: A total of 4,777 subjects were screened; 2,036 (43%) of them reported that they had been previously diagnosed as hypertensive. Of these, 1,954 (96%) were already on pharmacological treatment. A further 273 (5.7%) subjects were found to be hypertensive at screening. Among those receiving treatment, 1,399 (68.5%) had a blood pressure reading of less than 160/90 mmHg, and this was also the case for 59 (72%) of the known hypertensives not on treatment. A single drug was used by 1,556 (79.6%) of those on treatment. Risk factors for hypertension were more frequent in the hypertensive group (p 0.05 Pound). CONCLUSIONS: Almost half of the elderly population is hypertensive, most of them are already on treatment, but about one third of those on treatment do not have an adequate control of high blood pressure. PMID- 11763690 TI - [Validation of a self-efficiency scale for the prevention of AIDS among adolescents]. AB - OBJECTIVES: The objectives are obtain the internal consistency, validity and factorial structure of the Self-Efficacy for AIDS scale, which was developed in American population by Kasen, Vaughan and Walter (1992) and adapted in mexican samples for Lopez and Padilla (1999). INSTRUMENTS: It is employed the Self efficacy to Prevent the AIDS Scale of 27 items of Lopez and Padilla (1999), together with closed questions Likert type, dicotomics and two opened questions on relevant aspects of the sexual conduct to validate the scale, under a format self-applied test of pencil and paper. MATERIAL AND METHODS: It is a correlacional study with a not experimental design of transverse type. It was accomplished with a simple random sample of 962 adolescents wich were taken of 60 public health centers of Monterrey. None went to consult by motives related to the AIDS. RESULTS: The scale was adjusted to a normal distribution (Zk-s(Normal) = 1.369; p = 0.047). It presents a mean of 95.14 and a standard deviation of 25.80. Its reliability, by the alpha of Cronbach, was 0.89. SEA-27 shows a structure of four independent factors that explain 58.47% of the total variance. CONCLUSIONS: Thus, it is concluded that SEA-27 is a reliable and valid scale. PMID- 11763691 TI - [Prevalence of asthma and other allergic diseases in school children from Juarez City, Chihuahua]. AB - OBJECTIVE: To assess the prevalence and severity of asthma and allergic diseases in schoolchildren residing in Ciudad Juarez, Chihuahua. MATERIAL AND METHODS: A cross-sectional study was conducted from April 1998 to May 1999, among 6,174 children from 53 schools in Ciudad Juarez, Chihuahua. The method used was the one recommended by the International Study of Asthma and Allergies in Childhood (ISAAC) to determine the prevalence and severity of asthma, rhinitis, and eczema. Parents were asked to answer a standardized questionnaire on current and cumulative prevalence of asthma, rhinitis, and eczema. A sample stratified by level of pollution was selected. RESULTS: The cumulative prevalence of medically diagnosed asthma and wheezing was 6.8% (95% CI 6.2, 7.4) and 20% (95% CI 19.7, 21.8), respectively. The prevalence of wheezing in the last 12 months was higher in the group aged 6-8 years than in those aged 11-14 years (9.7% vs. 5.8%, p < 0.01). The prevalence of medically diagnosed rhinitis was 5.0% (95% CI 4.5, 5.6). The prevalence of medically diagnosed eczema was 4.9% (4.3, 5.4). The prevalence of eczema symptoms in the last 12 months was 12.7% in the 6-8 years group and 13.3% in the 11-14 year group, respectively. Severe symptoms of asthma were significantly higher in the 6-8 years group and during the autumn months. CONCLUSIONS: The prevalence of medically diagnosed and symptomatic asthma was relatively low in comparison with findings from others studies that use similar methods, but the prevalence rates of rhinitis and eczema were higher. PMID- 11763692 TI - [Learning from experience. Analysis of claims submitted to the National Commission of Medical Arbitration]. AB - OBJECTIVES: To describe claims brought to Comision Nacional de Arbitraje Medico (Medical Arbitration National Commission or Conamed) against medical care services in Mexico City. Also, to identify deficiencies in the quality of care by institution and medical speciality and describe some characteristics of the plaintiffs. MATERIAL AND METHODS: A total of 1925 claims were collected and data were analysed quantitatively. Pearson's chi-square (c2) test and a cluster analysis were performed. RESULTS: Most claims are related to therapy, surgery, and diagnosis problems. Claims related to structure, process, and outcomes were also identified for each defendant institution. Claims vary by sex, age, and socio-economic levels. CONCLUSIONS: Claims brought to Co-named are useful indicators of users' dissatisfaction. Our results are consistent with other papers about users' satisfaction and quality of health care. PMID- 11763693 TI - [Use of and verification with biological indicators in sterilizers belonging to dentistry surgeons from San Luis Potosi, Mexico]. AB - OBJECTIVE: To assess the utilization of sterilizing equipment used by dentists, and verification of sterilization using biological indicators. MATERIAL AND METHODS: A cross-sectional study was conducted in 1999-2000, among 130 (65%) dentists having sterilizing equipment, at Facultad de Estomatologia, Universidad Autonoma de San Luis Potosi and Colegio Dental Potosino. Biological indicators for sterilization containing Bacillus subtilis and Bacillus stearothermophilus were used. RESULTS: Thirty autoclaves and 100 dry-heat sterilizers were evaluated: 23 (17.7%) of them showed bacterial growth. Twenty-one (16.1%) dentists already were using biological indicators to verify their sterilizing equipment. Both sterilization methods were found to allow bacterial growth with similar frequencies (p = > 0.66). CONCLUSIONS: Few dentists verify the quality of sterilization process through biological indicators; bacterial growth and failure of sterilization were evidenced. PMID- 11763695 TI - [Epidemiologic overview of smoking in Mexico]. AB - Smoking is one of the main preventable causes of disease and death worldwide; 3.5 million smokers die annually. This essay shows the progress made against this epidemic in our country and points out the relevance of implementing a comprehensive program to control smoking. Results from three national surveys conducted in Mexico in 1988, 1993, and 1998 are analyzed and compared. On the one hand, the strategies should include preventive actions, protection of non smokers, smoking cessation, banning of smoking advertisement, and tax increases; on the other hand, controlling smoking and its consequences on health depend on all of us. PMID- 11763694 TI - [Prevalence of diabetes mellitus and hyperlipidemia among Otomi indians]. AB - OBJECTIVE: To determine prevalence and risk factors for diabetes mellitus (DM) and hyperlipidemias in a population of Otomi Indians. MATERIAL AND METHODS: A cross-sectional study was conducted between 1996 and 1997, in a convenience sample of 91 Otomi Indians, aged 15 to 77 years, in the communities of Yosphi and El Rincon, Queretaro, Mexico. Fasting blood samples were obtained to measure glucose, cholesterol and triglyceride levels. RESULTS: DM was found in 4.4% of subjects; hypercholesterolemia in 7.6%; and hypertriglyceridemia (HTG) in 26%. Mean concentrations of glucose -(81.0 +/- 24.4 mg/dl) and triglycerides (157.4 +/ 88.9 mg/dl) increased significantly with age, p = 0.0279 and p < 0.0001, respectively; as well as the prevalence of HTG (p < 0.0001). CONCLUSIONS: Results suggest that drastic changes in the diet of Otomi Indians may cause severe problems related to high concentration of lipids in blood. PMID- 11763696 TI - [Mystic, science, and politics in the development of health systems. The experience of Chile]. AB - The combination of inspiration, science, and politics is a cornerstone precept for the common good of humanity, towards the fulfillment of social objectives. Based on this precept, this paper reviews core experiences of the Chilean Health Sector. Health sector key events taking place during the first half of the 20th century were the creation of the National Health Service and the development of mother and child healthcare policies. After the earthquake of 1939, the future President of Chile, Doctor Salvador Allende, set up the Special Sanitation Council, to balance policies. Also, he launched the Social Security reform process, which endured financing restrictions and the animosity of physicians opposing the socialization of medical care. In 1951 the reform was approved, to extend coverage to blue collar workers and their families; separate health provision from healthcare security; emphasize preventive pediatric care in mother's health, and reproductive health. The basic tenets of healthcare reform were the right to health, solidarity, and equity, as the pillars of policy-making and healthcare programming. The question of whether the evolution of social security in Chile has been consistent with the original healthcare reform tenets is raised by the author. PMID- 11763697 TI - [Hospital discharge statistics of the Health Secretariat, 2000]. PMID- 11763698 TI - Reuse of single-use medical devices in Canadian acute-care healthcare facilities, 2001. PMID- 11763699 TI - The 2002 Joint Commission survey. An arduous mock survey can help you prepare. PMID- 11763700 TI - The rolled sandwich. A simple and versatile holiday treat. PMID- 11763701 TI - Executive leadership. A new age demands new skills. PMID- 11763702 TI - Gap analysis. A method for assessing leadership development needs. PMID- 11763703 TI - Medical gas safety. PMID- 11763704 TI - Introduction: cultures of neurasthenia from Beard to the First World War. PMID- 11763705 TI - 'Uterine mischief': W.S. Playfair and his neurasthenic patients. PMID- 11763706 TI - Public views of neurasthenia: Britain, 1880-1930. PMID- 11763707 TI - Neurasthenia in Wilhelmine Germany: culture, sexuality, and the demands of nature. PMID- 11763708 TI - Electrified nerves, degenerated bodies: medical discourses on neurasthenia in Germany, circa 1880-1914. PMID- 11763709 TI - The neurasthenic experience in imperial Germany: expeditions into patient records and side-looks upon general history. PMID- 11763710 TI - The public's view of neurasthenia in Germany: looking for a new rhythm of life. PMID- 11763711 TI - Neurasthenia in the Netherlands. PMID- 11763712 TI - Neurasthenia as Pandora's box? 'Zenuwachtigheid' and Dutch psychiatry around 1900. PMID- 11763713 TI - In search of Dutch neurasthenics from the 1880s to the early-1920s. PMID- 11763714 TI - A harmless disease: children and neurasthenia in the Netherlands. PMID- 11763715 TI - Nervousness, eighteenth and nineteenth century style: from luxury to labour. PMID- 11763716 TI - Neurasthenia and manhood in fin-de-siecle France. PMID- 11763717 TI - Claire, Lise, Jean, Nadia, and Gisele: preliminary notes towards a characterisation of Pierre Janet's psychasthenia. PMID- 11763718 TI - Varieties of medical experience: doctors and patients, psyche and soma in America. PMID- 11763719 TI - Neurasthenia in Britain: an overview. PMID- 11763720 TI - 'A mob of incoherent symptoms'? Neurasthenia in British medical discourse, 1860 1920. PMID- 11763721 TI - Leukotriene receptor antagonists (Montelukast) in the treatment of asthma crisis: preliminary results of a double-blind placebo controlled randomized study. AB - OBJECTIVE: Evaluate the efficacy of oral Montelukast 10 mg as an add-on therapy to the usual emergency therapy of an asthma crisis in an emergency room (ER). POPULATION: Twenty adults that sought medical attention in the ER of our Hospital and in whom, on admission, it appeared unnecessary to give systemic steroids. METHODS: All patients received the usual therapy of the asthma crisis. Simultaneously it was randomly administered a capsule containing 10 mg Montelukast or placebo, in a double-blind protocol. In both groups we evaluated the evolution of Peak-Flow values, the duration of stay in the ER as well as the need for additional therapy with systemic aminophylline or steroids, representing an insufficient response to the initial treatment. Student's T test was used to evaluate the statistical differences between these two groups. RESULTS: Both the Montelukast (MK) and Placebo (PL) groups were comparable regarding age and sex distribution, Peak-Flow values and Arterial O2 values on admission. During therapy, MK group had a shorter duration of ER stay (MK = 2.5 h; PL = 2.9 h) and a better evolution of Peak-Flow values (medium increase of 55% from baseline versus 44% in PL group). However these differences did not reach statistical significance. In the MK group one patient needed systemic steroids and 4 received systemic aminophylline while in the PL group 4 patients received systemic steroids and 8 aminophylline. This difference was significant (p = 0.03). We did not observe any significant side effects during therapy. CONCLUSIONS: Despite a small trend favourable to Montelukast we did not observe significant differences between groups regarding duration of stay or Peak-Flow evolution during therapy in ER, most probably due to the small sample size. However patients in the MK group needed significantly less systemic therapy with aminophylline or steroids. These data, in view of the very good safety profile of Montelukast, allow us to conclude that this is a useful additional therapy, which should be considered in the ER treatment of the asthma crisis. PMID- 11763722 TI - Effect of specific immunotherapy versus loratadine on serum adhesion molecules. AB - OBJECTIVE: To evaluate comparatively the effect on serum ICAM-1 and VCAM-1 values of specific immunotherapy versus loratadine in the treatment of allergic rhinitis. POPULATION: 65 patients with mild to moderate House Dust Mite allergic rhinitis. METHODS: Patients were divided into three groups, according to patients' preference: a control group with patients receiving only rescue therapy (antihistamines and/or nasal cromoglycate when needed); an antihistamine group with patients receiving daily loratadine 10 mg (and nasal cromoglycate as rescue therapy); an immunotherapy group with patients receiving subcutaneous house dust mite specific immunotherapy (and antihistamines or nasal cromoglycate when needed). In all groups we measured soluble ICAM-1 and VCAM-1 serum levels before the start of the study period and at the end of the study period. The duration of the study was one year for the control group and for the immunotherapy group. In patients taking daily antihistamines we measured serum adhesion molecules one month after the beginning of the therapy. We used Student's T test for statistical analysis. RESULTS: Patients in the control group didn't have significant variations in serum ICAM-1 (p = 0.239) or VCAM-1 (p = 0.38) levels. Patients receiving loratadine showed significant decreases in serum VCAM-1 levels (p = 0.0012) but not in serum ICAM-1 levels (p = 0.224). Patients receiving immunotherapy also showed a similar pattern, with significant decreases in serum VCAM-1 levels (p = 0.012) but not in serum ICAM-1 levels (p = 0.254). CONCLUSIONS: Specific house dust mite immunotherapy and regular daily loratadine therapy are able to lower significantly serum levels of soluble VCAM-1. However, this effect, which can be interpreted as an anti-inflammatory action, is not applied to soluble ICAM-1 levels, which raises the possibility of a differential action of these therapies on the mechanisms of allergic inflammation. Patients on rescue medication alone did not show any significant differences in these parameters. PMID- 11763723 TI - Immunotherapy in allergic rhinitis. AB - Allergen specific immunotherapy (IT) represents a cornerstone of allergic rhinitis treatment and his efficacy has been confirmed, through open and double blind trials and meta-analysis. In the last few years non invasive routs for IT (oromucosal, nasal) were developed gained general acceptation mainly in children and were validated by WHO. The efficacy of IT could be markers, the pattern of specific antibody response or by the effect on sequential nasal challenges. We have evaluated the effect of IT in allergic rhinitis by different methods. Nasal IT decreased mean symptoms and pharmacological scores as well as in seasonal as in perennial rhinitis. The same decrease has been observed after oromucosal IT. The effect of IT in allergic inflammation has been confirmed by a decrease in the level of soluble adhesion molecule sVCAM-1 which is related to eosinophilic inflammation but not statistically for sICAM-1. We have also evaluated the immunoblotting pattern or specific IgE after oromucosal IT for house dust mites. For D. pteronyssinus in 4 patients the bands intensity decreased and in 3 patients the bands decreased and in 10 disappeared. IT decreases tryptase and ECP in nasal lavage after sequential nasal challenges. Therefore IT decreases clinical scores, inflammation markers, specific IgE immunoblotting bands and response to allergen challenge. These different results confirm his efficacy and usefulness in allergic rhinitis. PMID- 11763724 TI - [Variation in eosinophilia and measures of pollen counts of grasses (Poaceae) and ragweed (Ambrosia) in the Rhone valley]. AB - Sensitivity to ragweed pollen, along with grasses pollen, is the leading cause of pollen-induced allergy in our region. Our study focuses on the variation of eosinophilia levels in the blood taken from a sample of the general population during both ragweed and grasses pollination periods. The pollen trap located in the central Rhone River Valley region has provided weekly counts since 1995. The Etablissement Francais du Sang Rhone-Alpes-Valence routinely checks hypereosinophilia in the blood through systematic analysis after a blood donation. Average cumulative pollen counts for grasses and ragweed present an interesting correlation with the levels of hypereosinophilia measured at the end of the summer. PMID- 11763725 TI - [Crossed food allergies in the Mediterranean: pollen and foods]. PMID- 11763726 TI - [Clinical profile and diagnosis of carbon monoxide poisoning]. PMID- 11763728 TI - [Heat contact urticaria: apropos of a case]. AB - Heat contact urticaria is a rare condition. We describe a case report and overview the literature about diagnosis and treatment of this pathology. PMID- 11763727 TI - [Mites and their allergens: identification and extermination methods]. AB - Mite allergens are the main allergens in indoor environment. Using different means of assessing exposure to house dust mites (Acarex-test, major allergen (Der p 1 + Der f 1, Der p 2 + Der f 2), content measured by ELISA) has allowed better identification of mite reservoirs and allergens in patients' homes. House dust mite control measures are based on the knowledge of factors contributing to mite development, especially indoor relative humidity. Mite allergen avoidance strategies include 3 different methods: avoidance of mite producing allergens, elimination of mite reservoirs, especially textile reservoirs, dwellings designed so as to inhibit mite proliferation. Only controlled trials can estimate patients' compliance with proposed avoidance measures. Avoidance protocols should be adjusted to each individual by medical indoor environment counselors in order to optimize mite allergen reduction. PMID- 11763729 TI - Intracranial abscessation in white-tailed deer of North America. AB - From January 1996 through April 1997, the geographic distribution, etiology, demographics, seasonality, and prevalence of an intracranial abscessation/suppurative meningoencephalitits syndrome in white-tailed deer (Odocoileus virginianus) were evaluated by surveying wildlife disease diagnostic laboratories and by examining both natural mortality and hunter-harvested deer skulls from North America. Intracranial abscesses were diagnosed as the cause of death or illness in 97 of nearly 4,500 (2.2%) white-tailed deer examined from 12 states and four Canadian provinces by the diagnostic laboratories. The bacterium Arcanobacterium pyogenes was isolated from 61% of cases; 18 other genera of bacteria also were isolated. The disease was strongly gender-biased (P < 0.01) with 87% of cases occurring in males, and the overall prevalence among males was 4.9%. Cases were most common among antlered males (> or = 1 yr) with few cases among male fawns. Among antlered males, cases were seasonal, primarily occurring from September through April. Four hundred eighteen skulls from deer found dead in the field were examined from southeastern USA, and of the 119 used for further evaluation, 9% had characteristic lesions. Skulls from hunter-harvested males in the southeastern USA had a lesion prevalence of 1.4%. The similarity of disease prevalence among male deer found dead in the field (9.0%) and deer examined as southeastern diagnostic laboratory cases (8.4%) suggests that this disease accounts for slightly < 10% of the natural mortality for yearling and adult male white-tailed deer in the southeastern region. The strong bias for occurrence among males suggests this disease may affect quality deer management strategies. PMID- 11763730 TI - Pathology of experimental mycoplasmosis in American alligators. AB - Mycoplasma alligatoris was the suspected etiology of an epidemic of acute multisystemic inflammatory disease which emerged in captive American alligators (Alligator mississippiensis) in Florida (USA) in 1995. In an experimental inoculation study conducted from April through October 1999, 18 alligators were inoculated with 10(2), 10(4), or 10(6) colony forming units (CFU) of M. alligatoris by instillation into the glottis. As early as 1 wk post-inoculation (PI), mycoplasma were cultured from blood of three of six alligators inoculated with 10(6) CFU. Two of those died and the third was euthanatized within 4 wk PI. Necropsy gross findings included fibrinous polyserositis and polyarthritis. Histopathologic changes in affected individuals included pulmonary edema, interstitial pneumonia, pericarditis, myocarditis, meningitis, and synovitis. Mycoplasma were cultured quantitatively in high numbers from trachea, lung, coelomic cavity, liver, spleen, interior of pericardial sac, heart, blood, brain, and limb joints. In alligators inoculated with 10(6) CFU, heterophilia and moderate hyperglycemia peaked about 4 wk PI, and seroconversion occurred by 6 to 8 wk PI. Necropsy gross and histologic findings were generally unremarkable for the surviving alligators inoculated with 10(6) CFU, alligators inoculated with 10(2) or 10(4) CFU, and four uninoculated control alligators. Mycoplasma were not cultured at any time point from those alligators. The findings confirm that M. alligatoris can cause fulminant inflammatory disease and rapid death of alligators. PMID- 11763731 TI - Electrocardiogram reference values for the buzzard in Spain. AB - Electrocardiographic reference values were established on apparently healthy buzzards (Buteo buteo) in Lugo (Spain) from March 1997 to June 1999. All birds were anesthetized with isofluorane and placed in dorsal recumbence. The standard and augmented unipolar limb leads electrocardiograms were recorded in 65 buzzards. The wave forms were analyzed in lead II at 50 mm/sec and at 1 cm = 1 mV to determine P, PR, QRS, T and QT durations and P, QRS and T amplitudes. The polarity of each wave form was tabulated in all leads. The mean electrical axis (MEA) for the frontal plane was calculated using leads II and III. The mean heart rate was 325.2 +/- 52.9 beats/min. In lead II, the P wave was positive, the dominant pattern of QRS complex was QS and the T wave was always positive. The average value of the MEA was -99.2 +/- 7.7 degrees. Establishment of normal electrocardiogram (EKG) values will facilitate a better understanding of EKG changes seen in many diseases of these birds. PMID- 11763732 TI - Effects of petroleum on mink applied as a model for reproductive success in sea otters. AB - Ranch-reared mink (Mustela vison) were used as a model in an experimental trial to investigate the potential effects of exposure to two petroleum products on sea otters (Enhydra lutris). Mink were exposed either dermally on one occasion 60 days prior to breeding or via low level contamination of their diets daily from 60 days prior to breeding (January 1994) until weaning of kits (June 1994). For dermal exposure, we placed mink in either a slick of Alaskan North Slope crude oil (n = 24) or bunker C fuel oil (n = 24) on sea water or sea water alone (n = 10) for 1 min. For dietary exposure, we fed mink rations containing 500 ppm of either Alaskan North Slope crude oil (n = 24) or bunker C fuel oil (n = 24; control, n = 15). The number of liveborn kits did not differ significantly among mink exposed dermally (5.0 kits/female for crude oil and 6.5 kits/female for bunker C fuel oil) and unexposed controls (5.3 kits/female). However, only 2.3 and 0.7 kits were produced per female for those exposed through the diet to crude oil and bunker C fuel oil, respectively. Females with reduced reproductive success had no clinical signs of toxicosis or behavioral abnormalities. In addition, kits of females exposed through the diet had poor survival to weaning. Once mature, kits born to females exposed to bunker C fuel oil in the diet had significantly reduced reproductive success (3.4 kits/female) although their only exposure to the petroleum products was in utero or during nursing. Therefore, it is possible that sea otter populations consuming contaminated food sources or colonizing previously oiled habitats will have reduced reproductive success. PMID- 11763733 TI - Concentrations and interactions of selected essential and non-essential elements in bowhead and beluga whales of arctic Alaska. AB - In this study, we evaluated concentrations of twelve essential and non-essential elements (As, Cd, Co, Cu, Pb, Mg, Mn, Hg, Mo, Se, Ag, and Zn) in tissues of bowhead (Balaena mysticetus) and beluga (Delphinapterus leucas) whales from arctic Alaska (USA) and northwestern Canada. Tissue samples were collected between 1983 and 1997, mostly in 1995-97. The essential elements are reported to develop reference ranges for health status determination, and to help assess known or suspected interactions affecting toxicoses of cadmium (Cd) and mercury (Hg). In some tissues, Cd, Hg, and selenium (Se) were present at concentrations that have been associated with toxicoses in some domestic animals. Nevertheless, tissue levels of all elements were within ranges that have been reported previously in marine mammals. While mean Ag concentrations in beluga whale liver were relatively high (15.91 micrograms/g ww), Ag was not associated with hepatic Se levels or age, contrary to previous findings. Significant associations included: Cd with age, Zn, or Cu; Cu with age, Zn or Ag; and Hg with age, Se, Zn, or Cu. This study found hepatic Hg:Se molar ratios to be consistently lower than unity and different between species. Possible explanations for observed elemental correlations (i.e., interactions) and ancillary mechanisms of Cd and Hg detoxification are discussed. PMID- 11763734 TI - Concentrations and interactions of selected essential and non-essential elements in ringed seals and polar bears of arctic Alaska. AB - In this study, we evaluated concentrations of twelve essential and non-essential elements (As, Cd, Co, Cu, Pb, Mg, Mn, Hg, Mo, Se, Ag, and Zn) in tissues of ringed seals (Phoca hispida) and polar bears (Ursus maritimus) of arctic Alaska (USA). All samples were collected between 1995-97 in conjunction with subsistence harvests. The essential elements are reported to help develop reference ranges for health status determination and to help assess known or suspected interactions affecting toxicoses of cadmium (Cd) and mercury (Hg). In some tissues, Cd, Hg, and selenium (Se) were present at concentrations that have been associated with toxicoses in some domestic animals. Nevertheless, tissue levels of all elements were within ranges that have been reported previously in other pinnipeds and polar bears. Significant associations included: Cd with Zn or Cu; Cu with Zn or Ag; and Hg with Se, Zn, or Cu. This study found hepatic Hg:Se molar ratios to be lower than unity and different between the two species. Based upon significant differences in mean tissue elemental concentrations for polar bear versus ringed seal, we concluded that biomagnification factors (bear/seal) were significant for: Cu in liver and muscle; Pb in kidney; Se in kidney and muscle; Zn in liver and muscle; and Hg in liver. Possible explanations for observed elemental correlations (i.e., interactions) and ancillary mechanisms of Cd and Hg detoxification are discussed. PMID- 11763735 TI - Duration of bluetongue viremia in experimentally infected American bison. AB - Six yearling American bison (Bison bison bison) bulls and one yearling ewe (Ovis aries) were inoculated intradermally and subcutaneously with 2 x 10(5) plaque forming units (pfu) of bluetongue (BT) virus serotype 11. Two uninoculated yearling bison bulls served as negative controls. Blood samples were collected for serology and virus isolation on 0, 4, 7, 11 and 14 days post-inoculation (dpi) and every 2 wk thereafter to 127 dpi. Every 4 wk a new ewe was inoculated with a pooled sample of whole blood from the six infected bison, and each sheep was monitored for 28 days for clinical signs of BT and seroconversion. Bluetongue viremia was detected in all six inoculated bison starting at 4 to 28 dpi and was no longer detectable from 42 dpi onward. Pooled blood samples collected at 28, 56, 84 and 112 dpi from the six infected bison were not infectious for sheep. The six infected bison seroconverted by 11 to 28 dpi on a competitive enzyme-linked immunosorbent assay and by 28 dpi on the serum neutralization test, and all remained seropositive thereafter. No clinical signs or lesions attributable to BT were observed in the infected bison or controls. There was evidence that a small amount of epizootic hemorrhagic disease virus type 2 had been present in the BT virus inoculum; reasons are given for concluding that this did not affect the results of the BT study. PMID- 11763736 TI - Acceptance of baits for delivery of oral rabies vaccine to raccoons. AB - During 1993-96 the Ontario Ministry of Natural Resources (Canada) implemented a research project to evaluate the efficacy of three candidate baits to deliver oral rabies vaccine to wild raccoons (Procyon lotor). Extensive field testing revealed that raccoon acceptance of Sugar-Vanilla baits (SV) at densities of 200/km2 and 400/km2, hand-placed in urban habitats of Scarborough (Ontario) during 1993, was 74% and 82%, respectively. Raccoon density in those areas averaged 11/km2. Aerial placement of SV baits in rural habitats in Barrie (Ontario) during 1993 and 1994, yielded raccoon acceptance levels of 58% with a density of 100 baits/km2, 59% at 75 baits/km2, and 47% at 50 baits/km2. Raccoon acceptance of SV baits was significantly lower in areas baited at the density of 50/km2. Acceptance of Cheese baits (CH) at a density of 75 baits/km2 was 52%. During 1996 trials in Barrie, modified SV baits with blister packs protruding through the matrix yielded raccoon acceptance values of 51% at a bait density of 54/km2, whereas acceptance of regular SV baits was 39% at a density of 51 baits/km2. Pooling of bait acceptance data for all years revealed that bait acceptance was highest for adult male raccoons. Raccoon density in rural habitats (Barrie, Ontario) where the studies took place, averaged 11-13/km2. Puncture and impact testing of blister packs in baits suggested that they would adequately serve as a vehicle to contain oral rabies vaccine for delivery to raccoons via baits. PMID- 11763737 TI - Serologic survey for canine coronavirus in wolves from Alaska. AB - Wolves (Canis lupus) were captured in three areas of Interior Alaska (USA). Four hundred twenty-five sera were tested for evidence of exposure to canine coronavirus by means of an indirect fluorescent antibody procedure. Serum antibody prevalence averaged 70% (167/240) during the spring collection period and 25% (46/185) during the autumn collection period. Prevalence was 0% (0/42) in the autumn pup cohort (age 4-5 mo), and 60% (58/97) in the spring pup cohort (age 9-10 mo). Prevalence was lowest in the Eastern Interior study area. A statistical model indicates that prevalence increased slightly each year in all three study areas. These results indicate that transmission occurs primarily during the winter months, antibody decay is quite rapid, and reexposure during the summer is rare. PMID- 11763738 TI - Susceptibility of the Siberian polecat to subcutaneous and oral Yersinia pestis exposure. AB - To determine if the Siberian polecat (Mustela eversmannii) represents a suitable model for the study of plague pathogenesis and prevention in the black-footed ferret (Mustela nigripes), polecats were exposed to 10(3), 10(7), or 10(10) Yersinia pestis organisms by subcutaneous injection; an additional group was exposed to Y. pestis via ingestion of a plague-killed mouse. Plague killed 88% of polecats exposed to Y. pestis (71% mortality in the 10(3) group, 100% mortality in the 10(7) and 10(10) groups, and 83% mortality in the mouse-fed group). Within the challenged group, mean day of death post-challenge ranged from 3.6 to 7.6 days; all polecats died on or before day 12 post-challenge. Animals receiving the lowest parenteral dose survived significantly longer than those receiving higher parenteral doses. Within challenged animals, mean survival time was lower in those presenting with significant weight loss by day 3, lethargy, and low fecal output; time to onset of lethargy and other signs was also related to risk of dying and/or plague dose. Six polecats developed serum antibody titers to the Y. pestis F1 protein. Three seropositive polecats survived the initial challenge and a subsequent exposure to a plague-killed mouse, while two seropositive animals later died. This study confirms that the Siberian polecat is susceptible to plague and suggests that this species will offer an appropriate surrogate for black-footed ferrets in future plague studies and related vaccine trials. PMID- 11763739 TI - Escherichia coli O157:H7 in free-ranging deer in Nebraska. AB - In order to determine the prevalence and distribution of the human pathogen, Escherichia coli O157:H7, in free-ranging deer, hunters were asked to collect and submit fecal samples from deer harvested during a regular firearm season (14-22 November 1998). Prior to the season, 47% of the hunters with permits in the southeastern Nebraska (USA) study area indicated a willingness to participate in the study. Approximately 25% of successful hunters in the area submitted deer fecal samples. Escherichia coli O157:H7 was cultured from four (0.25%) of 1,608 total samples submitted. All of the fecal samples that were properly identified (1,426) and all that were positive for E. coli O157:H7 were from white-tailed deer (Odocoileus virginianus). We were unable to detect a statistically significant geographic distribution pattern of E. coli O157:H7. The presence of E. coli O157:H7 in the feces of free-ranging deer has implications not only for hunters, consumers of venison, and others in contact with deer or deer feces, but also for the development of strategies aimed at reducing and/or controlling this pathogen in water sources and domestic livestock. PMID- 11763740 TI - New host and geographic records for two protostrongylids in Dall's sheep. AB - Biodiversity survey and inventory have resulted in new information on the distribution of Protostrongylidae in Dall's sheep (Ovis dalli dalli) from the Northwest Territories (NT, Canada) and from Alaska (AK, USA). In 1998, Parelaphostrongylus odocoilei adults were found for the first time in the skeletal muscles of Dall's sheep in the Mackenzie Mountains (NT). Adult P. odocoilei were associated with petechial and ecchymotic hemorrhages and localized myositis; eggs and larvae in the lungs were associated with diffuse granulomatous pneumonia. Experimental infections of the slugs Deroceras laeve and Deroceras reticulatum with dorsal-spined first-stage larvae assumed to be P. odocoilei, from ground-collected feces from Dall's sheep in the Mackenzie Mountains, yielded third-stage larvae by at least 28 (in D. laeve) and 48 (in D. reticulatum) days post-infection. Third-stage larvae emerged from D. laeve between days 19 and 46 post-infection and emergence occurred both at room temperature and at 10 to 12 C. Protostrongylus stilesi were definitively identified from the lungs of Dall's sheep collected in the Mackenzie Mountains, NT in 1998. Specimens collected from sheep in the Mackenzie Mountains, NT in 1971-72, and the Alaska Range, AK in 1972 were also confirmed as P. stilesi. Lung pathology associated with adults, eggs, and larvae of P. stilesi was similar to that described in bighorn sheep (Ovis canadensis). Concurrent infections with P. odocoilei and P. stilesi in a single host have not been previously reported. PMID- 11763741 TI - Experimental ivermectin treatment of sarcoptic mange and establishment of a mange free population of Spanish ibex. AB - Ivermectin was used to treat sarcoptic mange in Spanish ibex (Capra pyrenaica hispanica). Its therapeutic effectiveness was analyzed when it was administered through subcutaneous injection, to sick animals in the consolidation stage of mange (third phase) and, with double injections to chronically affected animals (fourth phase) at a dosage of 0.2 or 0.4 mg/kg body weight (bw). Three wk after treatment, the animals in the third phase of mange treated with a high dose (0.4 mg/kg bw) of ivermectin were completely cured. The same result was achieved after 4 wk of treatment in those animals in phase 3 of mange when 0.2 mg/kg body weight was used. Double injection with ivermectin, even at high doses, did not guarantee the complete cure of all cases of sarcoptic mange in the chronic stage (phase 4); only three of six animals were free of Sarcoptes scabiei. The second experiment consisted on the application of a sanitation program in order to obtain a population of Spanish ibex free from S. scabiei, starting with free-ranging animals, some of them healthy and others sick. After capture the animals were classified as chronically ill, in which case they were excluded from the program, mite carriers and healthy specimens. All the animals were treated first topically with foxim (500 mg/l) and subcutaneously with ivermectin (0.4 mg/kg bw). The infected animals were housed in the treatment pen, and received two doses of ivermectin (0.2 mg/kg bw) at an interval of 15 days, then spent 15 days in the quarantine pen, where they received a further dose before they were included in the pool of healthy animals, and immediately were placed in the quarantine phase. The sanitation we implemented was fully effective in curing the affliction of Spanish ibex affected by S. scabiei. PMID- 11763742 TI - Effects of spatial and host variables on hematozoa in white-crowned sparrows wintering in Baja California. AB - A survey of blood parasites was conducted in February 1995 on white-crowned sparrows (Zonotrichia leucophrys) wintering in two environmentally different localities of Baja California Sur (Mexico). Blood parasite prevalence was higher in La Purisima (49%) than in San Jose del Cabo (8%), but there were no differences between ages or sexes within each locality. All haematozoa infections were by Haemoproteus coatneyi, except one bird in each site that were positive for Trypanosoma sp. We found no evidence for the predicted negative relationship between host body condition and intensity of parasitism. The relatively high prevalence in one site suggests that an increase of hematozoa transmission may occur in that area. PMID- 11763743 TI - Serological responses of coyotes to two commercial rabies vaccines. AB - Between August 1993 and September 1994 we documented serological responses of coyotes (Canis latrans) vaccinated with two commercial rabies vaccines licensed for use in domestic dogs. Serologic responses were documented by testing for rabies virus neutralizing antibodies with the rapid fluorescent focus inhibition test (RFFIT) at 30, 90, 180, 270, and 365 days post-vaccination. All coyotes vaccinated with Imrab 3 (Rhone-Merieux, Inc.), and 75% of those vaccinated with Dura-Rab 3 (Immunovet, Inc.) seroconverted, as evidenced by the presence of antirabies antibody titers > or = 1:5 in one or more of the five post-vaccination samples. The percent of coyotes showing a titer > or = 1:5 was generally greater and titer levels appeared higher and more persistent among animals vaccinated with Imrab 3 than Dura-Rab 3. Presence of titers via RFFIT tests demonstrates the antibodies produced in coyotes by these rabies vaccines functionally bind and neutralize rabies virus in vitro, but these results do not constitute a demonstration of protection required for licensure for use in coyotes. PMID- 11763744 TI - European brown hare syndrome in free-ranging European brown and mountain hares from Switzerland. AB - From 1997 to 2000, complete necropsy and histopathologic investigations were performed on 157 free-ranging European brown hares (Lepus europaeus) found dead throughout Switzerland. Organ samples of all these individuals (157 livers and 107 spleens available) were tested for European brown hare syndrome virus (EBHSV) antigen by enzyme-linked immunosorbent assay (ELISA) test kit. Furthermore, 60 additional blood samples were tested for antibodies against EBHSV by ELISA. In addition, liver samples of 87 free-ranging mountain hares (Lepus timidus) hunted in 1996 were tested for EBHSV-antigen. In two European brown hares from southern Switzerland lesions suggestive of changes induced by EBHSV were present, and high titers of EBHSV-antigen were detected in both liver and spleen samples of these animals. Based on negative staining electron microscopy investigations of liver and spleen homogenates, we observed calicivirus in one antigen-positive hare. Low EBHSV-antigen titers were found in three additional European brown hares from central and western Switzerland, but EBHS-lesions were absent. Antibodies against EBHSV were not detected in any of the sera of European brown hares, and EBHSV antigen was not found in the samples of mountain hares. This is the first report of EBHS in European brown hares from Switzerland. PMID- 11763745 TI - Newcastle disease virus in double-crested cormorants in Alabama, Florida, and Mississippi. AB - In order to understand the epidemiology of Newcastle disease (ND) outbreaks in double-crested cormorants (Phalacrocorax auritus), a study was conducted on wintering migratory cormorants (P. a. auritus) in Alabama and Mississippi (USA) and non-migratory cormorants (P. a. floridanus) that breed in Florida (USA). Antibodies against ND virus were detected by the hemagglutination-inhibition method in sera from 86 of 183 (47%) migratory cormorants over-wintering in eight roosting sites in Alabama and Mississippi between November, 1997 and April, 1999. Titers ranged from 5 to 40. Antibody prevalences in sera collected from females in early winter (November and December) (26%) and late winter (February and March) (56%) were significantly different (P = 0.0007). None of 45 serum samples from 1- to 7-wk-old nestlings from 11 colonies in Florida during the 1997-98 and 1998-99 breeding seasons was positive. However, antibodies were detected in yolk samples from 98 of 126 (78%) eggs collected in these same colonies. Titers ranged from 4 to 256. The prevalence of antibodies in eggs collected from fresh-water colonies (63% prevalence, n = 30) and salt-water colonies (82% prevalence, n = 96) was significantly different (P = 0.041). ND virus was not isolated from tissues of 18 cormorants and cloacal and tracheal swabs from 202 cormorants collected in Alabama and Mississippi; virus was also not isolated from cloacal and tracheal swabs from 51 nestlings from Florida. PMID- 11763746 TI - Lingual calcinosis circumscripta in a captive sitatunga. AB - Calcinosis circumscripta (CC) was found in a 10-yr-old female sitatunga (Bovidae; Tragelaphus spekei). At necropsy, there were two white coalescing nodules (3 x 5 x 2 cm, 2 x 2 x 1.5 cm) on the ventral side of the tongue. The cut surface of the nodules had multiple, well-circumscribed loculi with chalky appearance and gritty consistency, separated by thin strands of connective tissue. Histologically, the nodules contained multiple loculi of various sizes and shapes, which consisted of amorphous material that was pale basophilic with H&E stain, surrounded by fibrous connective tissue. Around the loculi were numerous foreign body giant cells and epithelioid macrophages; occasional lymphocyte aggregations also were seen. The amorphous material was positive for PAS and von Kossa's stain. Calcinosis circumscripta is rare in the Bovidae. PMID- 11763747 TI - Malignant melanoma of the palpebral conjunctiva in a captive fallow deer. AB - A case of malignant melanoma in the conjunctiva of the eyelid of a captive 13-yr old female fallow deer (Dama dama) was studied. The black tumor that protruded to the palpebral conjunctiva of the right lower eyelid consisted of an infiltrative growth of melanin-containing neoplastic cells with marked cytological atypia. The tumor involved the conjunctiva of the right lower eyelid and infiltrated to the conjunctival epithelial layer, but did not reach the palpebral skin. Numerous mitotic figures and lymphatic invasions were observed. This is a very rare case of a malignant melanoma arising from the palpebral conjunctiva in a wild ruminant. PMID- 11763748 TI - Serologic evidence of influenza A infection in marine mammals of arctic Canada. AB - A serologic survey of influenza A antibodies was undertaken on 1,611 blood samples from five species of marine mammals collected from Arctic Canada from 1984-98. Sampling was done in 24 locations throughout the Canadian Arctic encompassing Sachs Harbor (72 degrees N, 125 degrees W), Northwest Territories in the west to Loks Land (63 degrees N, 64 degrees W), Nunavut in the east, to Eureka (80 degrees N, 86 degrees W), Nunavut in the north to Sanikiluaq (56 degrees N, 79 degrees W), Nunavut in the south. A competitive ELISA using a monoclonal antibody (Mab) against influenza A nucleoprotein (NP) was used. Five of 418 (1.2%) belugas (Delphinapterus leucas) and 23 of 903 (2.5%) ringed seals (Phoca hispida) were serologically positive. None of the 210 walruses (Odobenus rosmarus rosmarus), 76 narwhals (Monodon monoceros) and four bowhead whales (Balaena mysticetus) had detectable antibodies to influenza A. Positive belugas were identified from communities on southeast Baffin Island while positive ringed seals came from communities in the eastern, western and high Arctic. Virus isolation attempts on lung tissue from a seropositive beluga were unsuccessful. We believe that influenza A infection in marine mammals is sporadic, the infection is probably self-limiting, and it may not be able to be maintained in these animals. Although the predominant hemagglutinin (H) type was not determined and therefore the pathogenicity of the strains to humans is unknown, the hunting and consumption of marine mammals by the Inuit, may put them at risk for influenza A infection. PMID- 11763750 TI - Survey of aflatoxin concentrations in wild bird seed purchased in Texas. AB - The use of backyard feeders to attract avian wildlife is a common practice throughout the United States. However, feeding wildlife may create a problem due to aflatoxin, a harmful fungal metabolite, which can affect wildlife that are fed contaminated grain. Our study was initiated to determine if songbirds were being exposed to aflatoxin-contaminated feed throughout Texas. Bags of wild bird seed (n = 142) were purchased from grain cooperatives, grocery stores, and pet shops located in the panhandle, central, south, east, and west regions of Texas during spring and summer 1999. Aflatoxin concentrations in bird seed ranged from non detectable to 2,780 micrograms/kg. Overall, 17% of samples had aflatoxin concentrations greater than 100 micrograms/kg, of which 83% contained corn as an ingredient. Retail establishment effects were noted in the southern and western regions of Texas, with average concentrations of aflatoxin greater from bags of bird seed purchased from grain cooperatives, followed by pet shops, then grocery stores. Regional differences in aflatoxin levels were not apparent from bags of seed purchased at pet shops: however, regional differences were noted in aflatoxin levels from seeds obtained at grocery stores and grain cooperatives. Average aflatoxin concentration from seed purchased at grocery stores was greatest in the panhandle region, followed by the remaining regions. Within grain cooperatives, the panhandle, south, and west regions of Texas exhibited higher levels of aflatoxin-contaminated bird seed than cooperatives within the east and central regions of Texas. Granivorous songbirds in Texas are exposed to aflatoxins at backyard feeders, which may be a significant morbidity and mortality factor. PMID- 11763749 TI - Mycoplasmosis in evening and pine grosbeaks with conjunctivitis in Quebec. AB - An outbreak of conjunctivitis affected evening grosbeaks (Coccothraustes vespertinus) and pine grosbeaks (Pinicola enucleator) in Quebec (Canada) during the winter 1998-99. One to 30% of the individuals from these two species were sick at 13 feeding stations. Sick birds were thin and had unilateral or bilateral catarrhal and lymphoplasmacytic conjunctivitis and rhinitis, and mucopurulent infra-orbital sinusitis. Mycoplasmal organisms were isolated in cultures in an affected evening grosbeak and identified as Mycoplasma gallisepticum by direct immunofluorescence. Random amplified polymorphic DNA (RAPD) fingerprinting of this isolate resulted in a banding pattern that was identical to patterns of M. gallisepticum isolates made from similar lesions in house finches (Carpodacus mexicanus) and American gold finches (Carduelis tristis) throughout eastern North America. Mycoplasma gallisepticum was identified by polymerase chain reaction in another evening grosbeak and a pine grosbeak. These observations suggest that the same strain of M. gallisepticum is the likely etiology for the observed disease in evening and pine grosbeaks in Canada and represent an extension of the host species range for the ongoing epidemic of M. gallisepticum conjunctivitis in eastern North America. PMID- 11763751 TI - Ticks from a Morelet's crocodile in Belize. AB - Parasitism of crocodilians by ticks has rarely been reported, and to our knowledge only seven published accounts exist. On 3 July 1999, we collected four ticks from a subadult Morelet's crocodile (Crocodylus moreletii) captured in northern Belize. These were identified as Amblyomma dissimile (one female), and Amblyomma sp. (two nymphs, one larva). The crocodile was captured on land approximately 100 m from water, and all four ticks were attached to loose skin on the lateral surface of the tail. Crocodilians are most susceptible to terrestrial ectoparasites, including ticks, during overland movements. However, most such movements occur in response to drought, when tick questing activity is suppressed, which likely accounts for the small numbers of tick specimens recorded from crocodilians and the absence of any noticeable impact of parasitism on host fitness. PMID- 11763752 TI - Helminths of wild boar in Spain. AB - Forty-seven wild boars (Sus scrofa) collected from two areas in the province of Valencia (eastern Spain) were examined for digestive and respiratory helminth parasites. Helminth species and their prevalence were Taenia hydatigena cysticercus (19%), Ascarops strongylina (87%), Physocephalus sexalatus (6%), Ascaris suum (2%), Metastrongylus spp. (85%), Capillaria sp. (2%) and Macracanthorhynchus hirudinaceus (21%). Trichinella spp. were not found. Physocephalus sexalatus, A. suum, Capillaria sp. and M. hirudinaceus were found only in wild boars collected from one area (National Hunting Reserve of Cortes de Pallas). Macracanthorhynchus hirudinaceus did not occur in hogs < 1-yr-old, whereas the intensity of Metastrongylus spp. infection was the greatest in this age group. PMID- 11763753 TI - Emergency admissions. Change the record. AB - The rise in emergency admissions has been 2-3 per cent over the last 20 years and shows no sign of abatement. Medical emergencies account for most of the increase Emergency admissions should be divided into short and long stays. This type of analysis shows that the bulk of the increase in emergency admissions has been for short-stay patients. Better understanding of emergency admissions should help hospitals improve their ward distribution. PMID- 11763754 TI - Referrals. Electric avenue. AB - A pilot electronic booking project for outpatient appointments at King's College Hospital, London, has been well received by consultants. But only a minority of practices are taking part--only 24 of the 160 local practices are participating. A considerable culture change is needed to persuade practices to become involved. GPs accustomed to traditional referral letters find electronic referrals a big step. More day-to-day support might encourage GP involvement. PMID- 11763755 TI - Referrals. Practice pitch. PMID- 11763756 TI - Open space. Fault lines. PMID- 11763757 TI - Data briefing. Equity in healthcare. PMID- 11763758 TI - [Development of a regional program for prevention of children's disability]. AB - Pressing problems (social, socio-hygienic, medical, legal, etc.) of childhood disability are discussed for a typical Russian territory. Causes of disability from the viewpoint of its prevention are analyzed. Experience gained in organization of complex measures, inter-department approach to formation and realization of relevant programs with emphasis on prevention is presented on the model of the Republic of North Ossetia--Alania. PMID- 11763759 TI - [Health characteristics, quality of life and medical care of patients with diseases of the locomotor system (joint diseases and various types of osteochondrosis)]. PMID- 11763760 TI - [Medico-social aspects of primary disability due to cardiovascular diseases]. AB - The prevalence of primary disability caused by the major cardiovascular diseases was studied in Shymkent for the period of 1884-1995. The rate in the growth of this parameter is uneven; disability coefficient is 3-8-fold higher for men than for women. The need in extension of measures aimed at disability prevention and medicosocial rehabilitation is emphasized. PMID- 11763761 TI - [Morbidity trends in the population of Tatarstan Republic with basic socially important diseases]. AB - Main trends of changes in qualitative and quantitative parameters of socially significant contagious and noncontagious diseases (tuberculosis, syphilis, gonorrhea, HIV infection, acute respiratory infections, malignant tumors, mental disorders, narcological disorders, etc.), which essentially decrease the vital activity and working capacity of the Tatarstan population, are analyzed. The situation with regard to the above listed diseases deteriorated during the analyzed period. This can be altered only by wide-scale measures including medical care of patients, sanitization of various population groups making use of numerous methods of physical and mental rehabilitation and health fortification, and planned activities aimed at formation of a healthy life style. Determination of these tendencies is significant for evaluation of the health status of the population of Tatarstan Republic and can be used for scientific validation of regional programs of health protection and organization of medical care of the population. PMID- 11763762 TI - [State of reproductive health of boys in St. Petersburg]. AB - Complex medical social analysis of reproductive health of modern boys was carried out. Approaches to specialized care of boys and youths in St. Petersburg are presented. Measures aimed at creation of a universal staged specialized service including outpatient and inpatient care are offered. Standards were determined as regards care of boys with reproductive system disorders for primary health care centers and for the second component of specialized service, responsible for the major part of outpatient care. A comprehensive departmental system of medical care quality control is suggested, including public health administrative organs and clinical expert committees of treatment and prophylactic institutions. PMID- 11763763 TI - [Effects of sports on students' progress in studies]. AB - Relationship between health, athletics, and studies was evaluated in students of medical schools in Tatarstan. The empirical basis of the study was investigation carried out in 1997-1999 in Kazan, Naberezhnye Chelny, Nizhnekamsk, Elabuga, Almetyevsk, Chistopol, and Menzelinsk. First-, second, and third-year students took part in the study. The majority of medical students did not go in for sports at all. Students lagging behind in their studies predominated among athlets. These data indicate that health and effective studies are in inverse proportion and that vocational training, upbringing, medical examinations, treatment, and prophylactic examinations of students should be corrected individually with consideration for social and economic conditions. PMID- 11763764 TI - [Problems in population health statistics]. AB - The statistics of population health and development of public health system is incomplete. Mortality values can be analyzed for 5-year intervals, while morbidity is represented for the following age groups: children, adolescents, adults aged 20-39 and 40-59 years. The authors suggest revising the structure and volume of statistical data on morbidity with regard for age and sex for 5-year intervals, which will help more reliably and correctly solve modern problems of public health. PMID- 11763765 TI - [Legal regulation of maintenance provisions of a city hospital]. PMID- 11763766 TI - [Role of general hospitals in health services to population of a large city]. AB - Parameters characterizing public health activities in Chelyabinsk are analyzed. Time course of volume parameters characterizing the activities of multi discipline hospitals and analogous parameters for the whole city demonstrate their relationships and necessitate optimization of management of primarily large multi-discipline institutions. Among the elements of this optimization are planning of volume parameters of the treatment-and-prophylaxis institutions in accordance with the municipal order, revision of indications for hospitalization, control of validity of hospitalization, and improvement of managing technologies in outpatient clinics. PMID- 11763767 TI - [Social and financial aspects of rural medicine at municipal level]. PMID- 11763768 TI - [Current problems in advancement of health care of children and adolescents]. AB - Based on the results of socio-hygienic and medical organization research carried out at N. A. Semashko Institute, the authors discuss transformation of activities of a modern local pediatrician and addition of medical psychologist, adolescent therapist, and gynecologist to the staff of primary pediatric centers. Chronometric studies with evaluation of working time expenditures and estimation of the number of staff members helped determine standard staff for pediatric outpatient clinics. PMID- 11763769 TI - [Medical care of adolescents]. AB - The authors discuss staged transfer of adolescents aged 15-17 years to pediatric outpatient institutions by discontinuing their transfer to general therapeutic and prophylactic institutions and thus initiate continuous medical services for children till the age of 18 years within the framework of pediatric service. Experience gained in the Ryazan region is presented and the basic features in organization of public health organs and institutions of the territory in this direction are described; the role of complex prophylactic measures and inter departmental approach to solution of this problem are discussed. PMID- 11763770 TI - [Organizational bases of the advancement of telemedicine]. PMID- 11763771 TI - [Interrelations between the curricula of the Medical Institute and the Medical Department of the Moscow University in 1818-1834]. PMID- 11763772 TI - [Population health and economics factor]. AB - Correlations between gross domestic product per capita in terms of the minimum consumer goods basket and number of population health indicators is discussed for Kazakhstan. PMID- 11763773 TI - [Faculty Therapeutic Clinic of St. Vladimir University in late 19th and early 20th centuries: medical principles of Zakhar'in and Botkin in the activities of V. V. Chirkov and V. P. Obraztsov]. PMID- 11763774 TI - [Medical-demographic processes and rural family]. AB - Analysis of medical demographic parameters of the Nizhnii Ingash territory of Krasnoyarsk region is analyzed for the period of 1959-1999. Periods of changes (transformations) in the rural territory are distinguished. Time course of natural migration of population correlated with these periods. Number of children per rural family was estimated for the Krasnoyarsk region and Nizhny Ingash territory and the regularity of transformation of a traditional family with many children into a family with few children is described. Interviews of the population revealed the relationship between social reforms and reproductive policy of families. PMID- 11763775 TI - [Recombinant rearrangements of bacterial genome and adaptation to the environment]. AB - The rearrangement of bacterial chromosomes induced by intragenomic recombination is considered. The role of stochastic and programmed genome rearrangements in bacterial adaptation to the environment and in cell differentiation is discussed. PMID- 11763776 TI - [The role of antioxidant systems in response of bacteria Escherichia coli to heat shock]. AB - Shifting the temperature from 30 to 45 degrees C in an aerobic Escherichia coli culture inhibited the expression of the antioxidant genes katG, katE, sodA, and gor. The expression was evaluated by measuring beta-galactosidase activity in E. coli strains that contained fusions of the antioxidant gene promoters with the lacZ operon. Heat shock inhibited catalase and glutathione reductase, lowered the intracellular level of glutathione, and increased its extracellular level. It also suppressed the growth of mutants deficient in the katG-encoded catalase HPI, whereas the sensitivity of the wild-type and sodA sodB mutant cells to heat shock was almost the same. In the E. coli culture adapted to growth at 42 degrees C, the content of both intracellular and extracellular glutathione was two times higher than in the culture grown at 30 degrees C. The temperature-adapted cells grown aerobically at 42 degrees C showed an increased ability to express the fused katG-lacZ genes. PMID- 11763777 TI - [Isolation, purification, and separation of the complex preparation of extracellular proteinases with fibrinolytic and anticoagulant properties from Aspergillus ochraceus 513]. AB - The extracellular proteinase complex of the microscopic fungus Aspergillus ochraceus 513 was isolated, purified, and separated by affinity chromatography on bacillichin-silochrom and subsequent column chromatography on DEAE-Toyopearl 650 M. The extracellular enzyme of the protein C activator type had a molecular mass of 36.5 kDa and activity close to that of the Agkistrodon snake venom protein C activator. The fibrinolytic and anticoagulant activities of the enzyme were investigated. PMID- 11763778 TI - [Effect of reduced concentrations of carbon, nitrogen, and phosphorus in a medium on growth of three dissociants of Pseudomonas aeruginosa]. AB - The effect of lowered concentrations of carbon, nitrogen, and phosphorus sources in the medium on the specific growth rate mu of the R, S, and M dissociants of the hydrocarbon-oxidizing strain Pseudomonas aeruginosa K-2, culture pH, and the population composition was studied. Within the first 16 hours of cultivation in all of the four media tested, the R, S, and M dissociants had virtually identical mu. The maximal values of mu were reached by the 20th h of growth in the basal medium (R and S dissociants) and in the carbon-deficient medium containing 0.4% glucose (M dissociant). The R and M dissociants showed the most rapid decrease in mu in the nitrogen-deficient medium containing 0.55% NaNO3. By the end of cultivation in the basal medium, the pH of the R, S, and M cultures decreased to 6.3, 5.3, and 3.3, respectively. In the case of the carbon-deficient medium, the drop in the culture pH was lower. After a 2.5-day incubation of the S dissociant in the phosphorus-deficient medium containing 0.028% NaH2PO4.2H2O and of the M dissociant in the basal medium supplemented with chalk powder, these dissociants were completely displaced from the media. PMID- 11763779 TI - [Characteristics of exogenous dormancy of Aspergillus niger conidia]. AB - Aspergillus niger conidia are characterized by exogenous dormancy: the first stage of their germination is accomplished in twice distilled water. However, germ tube formation requires the availability of carbon and nitrogen sources. Exogenous dormancy in A. niger conidia exhibits the following peculiar features: (i) nitrogen-containing substances are active stimulators of germination; (ii) temperature-dependent changes in the lipid bilayer and in the neutral lipid composition of conidia are virtually identical to those occurring in growing mycelium under temperature stress; and (iii) the spore viability threshold does not exceed 45 degrees C; i.e., the spores are more heat-resistant than the mycelium, but they are less heat-resistant than the spores that are in the state of endogenous dormancy. According to the current classification of the types of cell metabolism arrest, the exogenous dormancy of A. niger conidia resembles the pattern of metabolism characteristic of vegetative cells during the idiophase. PMID- 11763780 TI - [Synthesis of anabiosis autoinducers in non-spore-forming bacteria as a mechanism regulating their activity in soil and subsoil sedimentary rocks]. AB - Non-spore-forming bacteria of the genera Arthrobacter and Micrococcus, isolated from permafrost subsoil, were found to produce greater amounts of the d1 extracellular factor than closely related collection strains isolated from soil. The effect of this factor, responsible for cell transition to anabiosis, was not species-specific. Thus, the d1 crude preparation isolated from the culture liquid of the permafrost isolate Arthrobacter globiformis 245 produced an effect on the collection strain Arthrobacter globiformis B-1112 and also on Micrococcus luteus and Bacillus cereus. The crude d1 preparation from the permafrost isolate of Arthrobacter differed from the chemical analogue of this factor, 4n hexylresorcinol, in the level of the induced cell response, which may have resulted from different cell sensitivity to various homologs of alkylhydroxybenzenes contained in the d1 preparation. Thus, additional evidence was obtained indicating that autoregulation of bacterial growth and development is implemented at the level of intercellular interactions in microbial communities. Abundant production of the d1 anabiosis-inducing factors by bacteria isolated from permafrost subsoil is probably a result of special antistress mechanisms responsible for the survival of these bacteria under extreme conditions of natural deep cooling. PMID- 11763781 TI - [Characteristics of in vivo isolation of free fatty acids by prokaryotic and eukaryotic algae under elevated and reduced temperature]. AB - The paper describes the composition of extracellular free fatty acids (FFAs) and intracellular fatty acids (FAs) in the enrichment cultures of the prokaryotic alga Spirulina platensis and the eukaryotic alga Chlorella vulgaris grown at optimal, supraoptimal, and suboptimal growth temperatures. With increasing growth temperature, the degree of unsaturation of the intracellular FAs of both algae decreased, while that of the extracellular FFAs of S. platensis increased. The composition of the extracellular FFAs of C. vulgaris practically did not depend on the growth temperature. PMID- 11763782 TI - [The role of chitinase in antifungal activity of Bacillus sp. 739]. AB - Investigation of the crude extracellular chitinase of Bacillus sp. 739, an antagonist of phytopathogenic fungi, discerned a relationship between the chitinase and antifungal activities of this bacterium. Purified chitinase lost its ability to inhibit the growth of micromycetes. The antagonistic (antifungal) activity of crude chitinase was found to be located in a low-molecular-weight fraction of the enzyme, which does not possess chitinase activity. Both crude and purified chitinase were able to lyse the cell walls of intact mycelium. Accordingly, it may be inferred that the antagonistic activity of Bacillus sp. 739 against micromycetes is largely determined by low-molecular-weight nonenzymatic substances whereas the role of chitinase is to utilize chitin, which is ubiquitously present in soil. PMID- 11763783 TI - [Pseudozyma fusiformata BKM Y-2821--a producer of antifungal glycolipid]. AB - The yeast Pseudozyma fusiformata (the order Ustilaginales) produces an extracellular low-molecular-weight protease-resistant thermostable fungicide, which was active against more than 80% of the 280 yeast and yeastlike species tested. The fungicide, extracted with methanol and purified by column and thin layer chromatography, was found to consist of glucose and saturated fatty acids. PMID- 11763784 TI - [Relationship between lectin, alpha-, beta-glucosidase, and beta-galactosidase activities of Azospirillum]. AB - The activities of alpha-glucosidase, beta-glucosidase, and beta-galactosidase were studied during the isolation and purification of lectins from Azospirillum brasilense Sp7 and Azospirillum lipoferum 59b cells. These enzymatic activities were revealed in crude extracts of surface proteins, protein fraction precipitated with ammonium sulfate or ethanol-acetone mixture, and protein fraction obtained by gel filtration on Sephadex G-75. The distribution of the enzymes between different protein fractions varied among the azospirilla studied. The cofunction of the A. brasilense Sp7 lectin and beta-galactosidase on the cell surface is assumed. A strong interaction between the A. lipoferum 59b lectin and glucosidases was revealed. The lectin from A. lipoferum 59b may possess saccharolytic activity. PMID- 11763785 TI - [Diversity in the monosaccharide composition of antigenic polysaccharides from proteobacteria Pseudoalteromonas and Marinomonas genera]. AB - The sugar analysis of the glycans of the type strains of marine proteobacteria of the genera Pseudoalteromonas and Marinomonas--Pseudoalteromonas atlantica IAM12927T, P. aurantia NCIMB 2033T, P. citrea ATCC 29719T, P. elyakovii KMM 162T, P. espejiana ATCC 29659T, P. piscicida NCIMB 645T, P. tetraodonis IAM 14160T, Marinomonas communis ATCC 27118T, and M. vaga ATCC 27119T--showed that they contain glucose, galactose, galactosamine, glucosamine, fucose, rhamnose, mannose, heptose, 2-keto-3-deoxyoctonate (KDO), uronic acids, colitose (3,6 dideoxyl-L-xylo-hexose), and 6-deoxy-L-talose. The carbohydrate composition of the antigenic polysaccharides (PSs) of P. elyakovii KMM 162T and P. espejiana ATCC 29659T depended on the type and the concentration of carbohydrate substrates in the nutrient media. The molar proportion between rhamnose, glucose, and galactose (ca. 1:0.3:2) in the PS of P. elyakovii KMM 162T was almost the same in the media lacking carbohydrates or containing glucose or galactose at a concentration of 1 g/l. At the same time, the molar proportion between fucose, glucose, galactose, galactosamine, and glucosamine (ca. 1:1:1:2:0.5) in the PS of P. espejiana ATCC 29659T depended on the presence and the concentration of carbohydrate substrates in the medium. A high concentration of glucose in the medium (30 g/l) brought about a rise in the content of glucose in PSs (9-fold for the PS of P. elyakovii KMM 162T and 4.6-fold for the PS of P. espejiana ATCC 29659T) and led to a decrease in the content of other carbohydrates. The cultivation of these two strains at a lactose concentration of 30 g/l resulted in their PSs containing glucose and galactose in about equal proportions (ca. 1:1 in the case of P. espejiana ATCC 29659T and ca. 2.1:1.7 in the case of P. elyakovii KMM 162T). PMID- 11763787 TI - [Formation of polar bundles of pili on a cell and the behavior of Azospirillum brasilense in semiliquid agar]. AB - This paper describes the formation of single polar bundles of pili on Azospirillum brasilense cells, the twitching motility of cell aggregates, and a new type of social behavior--the dispersal of bacterial cells in semiliquid agar associated with the formation of granular inclusions (the so-called Gri+ phenotype)--which is an alternative to swarming (the Swa+ phenotype). The wild type A. brasilense cells occurring in a semiliquid agar may show either the Swa+Gri-, or Swa-Gri-, or Swa-Gri+ phenotype. The formation of single polar flagella (Fla) or polar bundles of pili may reflect two alternative states of A. brasilense cells. The components of the Fla system may be involved in the regulation of the phenotypic variation of azospirilla. PMID- 11763786 TI - [Lysozyme-antilysozyme interactions in protozoa-bacteria communities (a model Tetrahymena-Escherichia community)]. AB - Lysozyme and antilysozyme activities present in a wide range of microorganisms determine the so-called lysozyme-antilysozyme system of hydrobionts, which greatly contribute to the formation of aquatic biocenoses. However, the mechanism of the functioning of this system in natural freshwater communities remains obscure. The experimental investigation of lysozyme-antilysozyme interactions in a model Tetrahymena--Escherichia community showed that the antilysozyme activity of Escherichia coli leads to incomplete phagocytosis, thus enhancing bacterial survival in a mixed culture with infusoria. The selection and reproduction of bacterial cells resistant to grazing by infusoria determine the character of host parasite interactions and allow bacteria to survive. It was demonstrated that the antilysozyme activity of microorganisms, which is responsible for bacterial persistency in natural biocenoses, is involved in the maintenance of protozoa bacteria communities in bodies of water. PMID- 11763788 TI - [Identification of Zygowillopsis californica strains of various origin by polymerase chain reaction with universal primers]. AB - After reevaluation of the taxonomic position of 27 yeast collection strains of different origin by UP-PCR followed by dot-hybridization, only 22 strains were assigned to the biological species Zygowilliopsis californica (Lodder) Kudriavzev. Four strains were identified as Williopsis suaveolens (Klocker) Naumov et al. Universal primers L45 and N21 are recommended for identification of the Z. californica yeasts. PMID- 11763789 TI - [Microbial processes of carbon and sulfur cycles in lake Mogil'noe]. AB - In the beginning of summer 1999, complex microbiological and biogeochemical investigations of meromictic Lake Mogil'noe (Kil'din Island, Barents Sea) were carried out. The analysis of the results shows clearly pronounced vertical zonality of the microbial processes occurring in the water column of the lake. To a depth of 8 m, the total number and activity of microorganisms was limited by the relatively low content of organic matter (OM). In the upper part of the hydrogen-sulfide zone of the lake (beginning at a depth of 8.25 m), the content of particulate OM and the microbial number sharply increased. In this zone, the daily production of OM during anaerobic photosynthesis at the expense of massive development of colored sulfur bacteria reached 620 mg C/m2, which was twofold greater than the daily production of phytoplankton photosynthesis and led to a considerable change in the isotopic composition (delta 13 C) of the particulate OM. In the same intermediate layer, the highest rates of sulfate reduction were recorded, and fractionation of stable sulfur isotopes occurred. Below 10 m was the third hydrochemical zone, characterized by maximum concentrations of H2S and CH4 and by a relatively high rate of autotrophic methanogenesis. The comparison of the results obtained with the results of investigations of previous years, performed in the end of summer, shows a decrease in the intensity of all microbial processes inspected. An exception was anoxygenic photosynthesis, which can utilize not only the de novo formed H2S but also the H2S accumulated in the lake during the winter period. PMID- 11763790 TI - [Enumeration of active cells in bacterial plankton of the Rybinsk reservoir with 5-cyano-2,3-ditolyltetrasolium: comparison with other methods]. AB - The enumeration of actively respiring bacterial cells in different biotopes of the littoral zone of the Rybinsk Reservoir during the spring period of ice thaw using the fluorescent dye 5-cyano-2,3-ditolyl tetrazolium chloride showed that bacterial communities growing on the bottom surface of the ice cover and in water overgrown by higher aquatic plants were most active. The number of active cells among individual bacterial cells averaged 20% and reached about 40% among aggregated and filamentous bacterial cells. The results of the count of active bacteria by this method were compared with those obtained by other methods. PMID- 11763791 TI - [Structure of bacterial complexes of the river Protva flood-plains]. AB - The synecological analysis of bacterial communities from the Protva River flood plain biogeocenosis showed that all of the horizons contain spirilla, which are typical hydrobionts, and pigmented coryneform bacteria associated with the herbaceous plants of the flood-plain meadows. The alluvial meadow soils of the inundated regions of the floodplain differed from the unflooded regions of the flood-plain in that they had a more diverse bacterial population continuously distributed over the soil profile. PMID- 11763792 TI - [Formation of artificial nitrogen-fixing symbiosis with rape (Brassica napus var. napus) plants in nonsterile soil]. AB - The treatment of rape plants grown in nonsterile soil with 2,4 dichlorophenoxyacetic acid (auxin-like growth-promoting substance) or their inoculation with the bacterial association Micrococcus sp. + Rhodococcus sp. and/or with the mixed nitrogen-fixing culture Azotobacter nigricans + Bacillus sp. led to the formation of paranodules on the rape roots. The introduced bacteria were detected both in the intercellular space and inside the cells of the paranodules and the rape roots. The nitrogen-fixing activity of the paranodulated plants was two times higher than that of the inoculated plants lacking paranodules and five times higher than that of the control (i.e., not inoculated) plants. The paranodulation led to a 40% increase in the crop yield of rape plants and provided for a statistically significant increase in the total nitrogen as well as protein nitrogen contents of the plants. PMID- 11763793 TI - [Distribution of microscopic fungi along Moscow roads]. AB - The distribution of microscopic fungi in soils and surface air along some Moscow roads was studied from 1994 through 2000 at several distances (0, 5, 10, and 20 m) from the roads. Soil fungal complexes in roadside zones with different levels of pollution from automobile engines were found to differ in their composition, species structure, and biomorphology. Relatively far from the roads, the content of fungal mycelium diminished, while that of fungal spores increased. Close to the roads, fungal complexes in soil and surface air were dominated by dark melanin-containing fungi. The microscopic fungal complexes of soil and surface air along the roadsides were similar but differed in the relative abundance of some species. PMID- 11763794 TI - [Yeast biodiversity in hydromorphic soils with reference to grass-Sphagnum swamp in Western Siberia and the hammocky tundra region( Barrow, Alaska)]. AB - The microbiological analysis of 78 samples taken from a boreal bog in Western Siberia and from a tundra wetland soil in Alaska showed the presence of 23 yeast species belonging to the genera Bullera, Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Metschnikowia, Mrakia, Pichia, Rhodotorula, Saccharomyces, Sporobolomyces, Torulaspora, and Trichosporon. Peat samples from the boreal bog were dominated by eurytopic anamorphic basidiomycetous species, such as Rhodotorula mucilaginosa and Sporobolomyces roseus, and by the ascomycetous yeasts Candida spp. and Debaryomyces hansenii. These samples also contained two rare ascomycetous species (Candida paludigena and Schizoblastosporion starkeyi henricii), which so far have been found only in taiga wetland soils. The wetland Alaskan soil was dominated by one yeast species (Cryptococcus gilvescens), which is a typical inhabitant of tundra soils. Therefore, geographic factors may serve for a more reliable prediction of yeast diversity in soils than the physicochemical or ecotopic parameters of these soils. PMID- 11763795 TI - CDC broadcast aims to improve clinicians' grasp of anthrax issues. PMID- 11763796 TI - Special health care team screens postal workers for anthrax. PMID- 11763797 TI - Pharmacy products could be on bomb makers' shopping lists. PMID- 11763798 TI - Tragic experience sends pharmacist back to his profession. PMID- 11763799 TI - Oral budesonide approved for active Crohn's disease. PMID- 11763800 TI - Eflornithine. PMID- 11763801 TI - Valganciclovir hydrochloride. PMID- 11763802 TI - Vital signs of quality: medication-use safety. PMID- 11763803 TI - Ciprofloxacin frenzy. PMID- 11763804 TI - ASHP national survey of pharmacy practice in hospital settings: prescribing and transcribing--2001. AB - Results of the 2001 ASHP national survey of pharmacy practice in hospital settings that pertain to prescribing and transcribing are presented. A stratified random sample of pharmacy directors at 1091 general and children's medical surgical hospitals in the United States was surveyed by mail. SMG Marketing Group, Inc., supplied data on hospital characteristics; the survey sample was drawn from SMG's hospital database. The response rate was 49.0%. During 2001, nearly all hospitals are estimated to have pharmacy and therapeutics (P&T) committees that meet an average of seven times per year. It is estimated that more than 90% of P&T committees are responsible for formulary development and management, drug policy development, adverse-drug-reaction review, and medication use evaluation. More than 90% of hospitals use clinical and therapeutic, cost, and pharmacoeconomic information in the formulary management process, while nearly two thirds consider quality-of-life issues. Nearly 70% use clinical practice guidelines in the formulary management process, and 78% have a medication-use evaluation program designed to improve prescribing. Pharmacists in more than 75% of hospitals provide consultations on drug information, dosage adjustments for patients with renal impairment, antimicrobials, and pharmacokinetics. Further, a majority of hospitals ensure accurate transcription of medication orders by clarifying illegible orders before transcription or entry into medication administration records (MARs), using standardized prescriber order forms, requiring prescribers to countersign all oral orders, and reconciling MARs and pharmacy patient profiles at least daily. In 2001, large hospitals are most likely to use prescriber order-entry systems to improve patient safety and are least likely to require the reentry of medication orders into the pharmacy computer system. The 2001 ASHP survey results suggest that pharmacists in hospital settings have positioned themselves well to improve the prescribing and transcribing components of the medication-use process. PMID- 11763805 TI - Automated medication distribution systems and compliance with Joint Commission standards. AB - One health care institution's experience with an automated medication distribution (AMD) system is described, along with how the system met standards of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). AMD units were implemented in nearly 50 patient care locations in a medical center with the goal of providing cartless distribution for over 90% of all medications. Planning for the system began in the fall of 1998; the system was fully implemented by mid-2000. In compliance with JCAHO requirements, the system provided medications in unit dose or single unit-of-use packaging, supplied drugs in a ready-to-administer form, ensured that drugs were available only near the time of administration, created a patient-specific medication profile, allowed for pharmacist review of medication orders before dispensing, provided proper storage conditions, prevented unauthorized use, allowed for access in emergencies, and met federal and state regulations. Implementation of the system improved drug distribution at the medical center and saved nursing and pharmacy time. Challenges included waits by nurses trying to access the AMD units and the extensive, ongoing education and training required for users of the system. An AMD system should be fully integrated with the health care institution's medication-use process and comply with applicable JCAHO standards. PMID- 11763806 TI - Pharmacy preparedness for incidents involving weapons of mass destruction. AB - Recent worldwide terrorist acts and hoaxes have heightened awareness that incidents involving weapons of mass destruction (WMD) may occur in the United States. With federal funding assistance, local domestic preparedness programs have been initiated to train and equip emergency services and emergency department personnel in the management of large numbers of casualties exposed to nuclear, biological, or chemical (NBC) agents. Hospital pharmacies will be required to provide antidotes, antibiotics, antitoxins, and other pharmaceuticals in large amounts and have the capability for prompt procurement. Pharmacists should become knowledgeable in drug therapy of NBC threats with respect to nerve agents, cyanide, pulmonary irritants, radionucleotides, anthrax, botulism, and other possible WMD. PMID- 11763807 TI - Neuromuscular blockers in surgery and intensive care, Part 1. AB - The historical development, pharmacology, pharmacodynamics, pharmacokinetics, clinical applications, pharmacologic basis for selection, adverse effects, and cost of neuromuscular blockers (NMBs) are discussed. The first NMB to be used was tubocurarine. During neurotransmission, acetylcholine is synthesized, stored in vesicles at the neuromuscular junction, released into the synapse, and bound to nicotinic receptors in the muscle end plate. For muscle contraction to occur, the impulse generated in a neuron's cell body must create an action potential that is chemically transmitted across the synapse. The postsynaptic nicotinic receptor at the neuromuscular junction is the major site of action of depolarizing and nondepolarizing NMBs. All NMBs have the potential for cross-reactivity at other nicotinic and muscarinic sites. Drug interactions most commonly occur between NMBs and inhalation anesthetics, certain antimicrobials, calcium-channel blockers, and anticholinesterases. When selecting an NMB, an agent's onset and duration of action must be considered. NMBs can be used on a short-term or long term basis. Apart from cost, the choice of an NMB is made on the basis of its adverse-reaction profile, pharmacokinetics, and indications for use. Monitoring tools, their use, the rationale for their use, and the interpretation of the results they provide are unique. The patterns of peripheral nerve stimulation vary and elicit different characteristics of nondepolarizing neuromuscular blockade. The effectiveness of reversal agents is proportional to the degree of blockade. The mechanism of action of anticholinesterases involves inhibition of acetylcholinesterase. The expensive NMBs should be conserved for use in surgery, while the cheaper, long-acting [corrected] agents should be used in the intensive care unit. An understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of NMBs will help health care providers gain expertise in the selection and use of these agents. PMID- 11763808 TI - Seaweed, vitamin K, and warfarin. PMID- 11763809 TI - Meeting of oncology residency program directors. PMID- 11763810 TI - Pharmaceutical services for indigent patients. PMID- 11763811 TI - [Parasternal lymph node excision in breast cancer]. AB - Comparative analysis of the results of videothoracoscopic parasternal lymphadenectomy and standard mastectomy by Urban--Holdin is presented. In November 1995 to December 1999 205 videothoracoscopic parasternal lymphadenectomies were performed (96--on the left, 104--on the right). Central and medial location of breast cancer was indication for this operation. Age of the patients ranged from 23 to 73 years. Surgery was performed under intravenous anesthesia in the conditions of artificial lung ventilation with separate lung intubation. Mastectomy was performed as the first stage. Further, thoracoports were introduced into pleural cavity in the 5th intercostal space along medioclavicular and mediaxillar lines and in the 4th intercostal space along anterior axillar line. Parietal pleurotemy was performed parallely to internal thoracic vessels, parasternal fat and lymph nodes were removed en-block. Parasternal lymph nodes were involved in 40 (19.5%) patients. The spirometry, cardiomonitoring which were used pre-, intra-, postoperatively demonstrated that parasternal thoracoscopic lymphadenectomy is less traumatic and effective as diagnostic method than mastectomy by Urban--Holdin. Parasternal thoracoscopic lymphadenectomy can be recommended as a method of choice in medial and central breast cancer. PMID- 11763812 TI - [Treatment of ischemic heart disease by minimally invasive coronary surgery with the "Octopus" system]. AB - Results of 30 operations performed for combined lesions of coronary and peripheral arteries are analyzed. All the operations were performed as off-pump minimally invasive coronary surgery (MICS) on beating heart with "Octopus" system Medtromic. There were no lethal outcomes. Number of complications was minimal. MICS is high-effective procedure in selected patients with coronary heart disease. It is necessary to use differential policy of surgical treatment of coronary heart disease. PMID- 11763813 TI - [Ultrasonic diagnosis of abdominal foreign bodies]. AB - Experience with ultrasonic examination (USE) in diagnosis of foreign abdominal bodies in 23 patients is reviewed. Foreign abdominal bodies have specific echosemiotics. It is demonstrated that USE provides maximal information about sizes, structure, location of foreign abdominal bodies, their depth of location and relationship with abdominal organs. It makes sense to make in some cases a differential diagnosis with inflammatory infiltrates and abdominal abscesses, fetus, gastric bezoar. It is necessary for this to use additional X-ray and endoscopic methods. USE helps to decide on optimal surgical approach and gives information for repeated surgery that permits to reduce the time of relaparotomy. PMID- 11763814 TI - [Functional results of laparoscopic antireflux surgery and causes of postoperative dysphagia]. AB - Results of functional examination of 176 patients with gastroesophageal reflux disease are presented. 94 patients were were followed up from 1 month to 4 years after laparoscopic antireflux operation (82--by Nissen and Nissen--Rossetty, 6- by Dor, 6--by Toupet). After Nissen operation the pressure in the region of lower esophageal sphincter (LES) increased more than after partial fundoplication and remained the same during 4 years of follow-up (p < 0.05). Postoperative dysphagia in the majority of cases was associated with excessive increase of pressure and length of LES region, decrease of it capacity to relaxation during swallowing (p < 0.05). 360 degrees-fundoplication can not be recommended only in complete loss of contractile capacity of the esophagus. PMID- 11763815 TI - [The role of helminthiasis in the etiology of acute appendicitis]. AB - 279 vermiform processes removed for different form of appendicitis were studied hystologically with obligatory analysis of appendix content. High rate of helminth intestation (27.2%) in vermiform processes removed in acute appendicitis surgery confirms an important role of small helminths (Enterobius, Trichocephalis and their larvae) in acute appendicitis development. The incidence of acute appendicitis and helminths interstation in children is higher than in adults. All the patients with acute appendicitis need helminthological examination and etiotropic treatment because appendectomy eliminates the complication but not the cause of intestinal disease. PMID- 11763816 TI - [Assessment of the results of surgical treatment of multiple lesions of lower limb arteries]. AB - 121 one-stage "two-floor" reconstructions were performed in multiple lesions of lower limbs arteries. Their results were compared with results of 197 reconstructions of aorto-iliac segment with revascularisation of the firifory of deep femoral artery (DFA). In immediate postoperative period better results were achieved after one-stage "two-floor" reconstructions. There were 70.9% of good results after revascularisation of DFA and 88.4%--after one-stage "two-floor" reconstructions. In long-term period (up to 5 years) after "two-floor" reconstructions the patency of the distal bypasses was lower than that of proximal bypasses since the second year of follow-up. Patency of the distal bypasses after one-stage "two-floor" reconstructions depends on a type of plastic material, location of distal anastomosis of the femoro-popliteal bypass and does not depend on location of the proximal anastomosis. Patency of combined bypasses was lower than one of autovenous bypasses and biografts since the second year of follow-up, patency of femoro-tibial bypasses was lower than that of femoro popliteal bypasses since the third year of follow-up. PMID- 11763817 TI - [Peripheral hemodynamics in patients with posttraumatic osteomyelitis of leg bones]. AB - Complex examination of peripheral hemodynamics with rheovasography, US dopplerography and laser flowmetry was carried out in 67 patients with posttraumatic osteomyelitis of leg bones. In these patients before treatment there were sings of functional spasm of popliteal artery, increase of circulatory resistance in the bed of anterior and posterior tibial arteries, decrease of precapillary vessels reactivity by hypertonic type, decrease of capillary elasticity, their spasm, difficulty of blood outflow from great and middle veins. During treatment by transsosseous osteosynthesis main-changed type of blood flow, unstable vascular tones, decrease of greater artery elasticity, hypertoe of pre- and postcapillary small vessels were found. After treatment normalization of vascular tone, balance of status of pre- and postcapillary vessels, normal reaction of capillaries to functional test were demonstrated. PMID- 11763818 TI - [Comparative assessment of diagnostic methods in adenomas of the thyroid gland]. AB - The authors carried out comparative assessment of sensitivity and specificity of ultrasonic examination with color dopper mapping (USE with CDM), thin-needle aspiration biopsy--TAB (palpation- and US-assisted), express histologic examination--(EHE), intraoperative laser autofluorescent spectroscopy (IOLAS) with retrospective assessment by results of elective histologic examination in adenomas of thyroid gland (TG). Medical histories of 135 patients hospitalized with adenomas of TG of follicular cells were analyzed. Based on comparison of USE with CDM and morphologic analysis of TG adenomas three types of specific echographic symptomcomplexes were recognized. USE with CDM in combination with US assisted TAB was the most effective diagnostic complex before operation. Comparative analysis of results of these methods with express histologic examination showed equal efficacy, that permitted to reject routene EHE. For the first time IOLAS was used as "optic instant-biopsy" for selection of optimum scope of surgery when "follicular neoplasia" was suspected. Combined use of USE with CDM and TAB before operation as well as IOLAS enabled correct diagnosis of the nature of TG lesion, it morphologic type, and based on these data adegnatechoice. PMID- 11763819 TI - [Surgical treatment of complicated extra-sphincter and trans-sphincter fistulas of the rectum]. AB - 172 patients were operated for complicated extrasphincter high fistulas and some transsphincter fistulas of the rectum. All the patients were treated by the proposed method--resection of the fistula in intestinal lumen, splitting of the sphincter, repair of anal canal with pullthrough of the distal rectal segment. Spinal anesthesia leading to good relaxation of the anal canal was used. There were no recurrences in patients folloved up during 2 years. Postoperative bed-day reduces to 12-15. There were no disorders of rectal sphincter apparatus. PMID- 11763820 TI - [Thienam treatment in early postoperative period after pneumonectomy in patients with lung cancer]. PMID- 11763821 TI - [H2 blockers in the treatment of bleeding gastroduodenal ulcers]. PMID- 11763822 TI - [Surgical treatment of a patient with giant pheochromocytoma]. PMID- 11763824 TI - [Use of physical methods in the treatment of purulent wounds]. PMID- 11763823 TI - [Transcutaneous rheolytic thrombectomy in combination with stenting of distal anastomosis in thrombosis of femoro-popliteal bypass]. PMID- 11763825 TI - Physicians' attitudes toward litigation and defensive practice: development of a scale. AB - The authors' threefold purpose in this article was to (a) propose a model of the relationship between the emotional aspects of physicians' attitudes to medical errors (e.g., fear of litigation) and their functional consequences (e.g., tendency to defensive practice); (b) develop a measure of some of these attitudes; and (c) provide empirical support for some of the relationships in the model. Medical students and physicians responded to a questionnaire concerning their attitudes toward uncertainty and medical error. The dependent variables were two dimensions of attitudes to uncertainty ("reluctance to disclose uncertainty" and "stress from uncertainty") and four dimensions of attitudes to medical error ("fear of litigation," "support for self-regulation," "tendency to defensive practice," and "self-disclosure of errors"). Stress from uncertainty correlated with fear of malpractice litigation and defensive practice. They concluded that interventions that aim to increase physicians' tolerance of uncertainty may also reduce their fear of malpractice litigation and their tendency to defensive practice. PMID- 11763826 TI - Acculturation and family functioning are related to health risks among pregnant Mexican American women. AB - The authors examined the independent and interactive effects of acculturation status and family cohesiveness on a series of psychosocial and medical risk factors of pregnancy among 500 women of Mexican origin. In general, both higher and lower levels of acculturation produced positive or negative psychosocial and healthcare consequences, and the operative relationships depended heavily on the particular outcome chosen. Higher levels of family cohesiveness tended to foster the most constructive health and psychosocial outcomes. However, in some circumstances higher levels of family cohesiveness resulted in less coping and a lower quality of prenatal care for less acculturated women. An important implication of this study is that psychosocial and health information can be obtained through assessments that identify different subgroups of Mexican American women and depend on women's level of acculturation and family cohesiveness. Culturally competent health practitioners or clinicians can conduct these assessments in a prenatal healthcare setting. PMID- 11763827 TI - The prevalence of daytime napping and its relationship to nighttime sleep. AB - Many healthy adults report daytime napping. Surprisingly few studies, however, have examined spontaneous napping behavior, especially very short naps, in healthy adults. The authors examined the prevalence of power naps (lasting less than 20 minutes) and longer naps (20 minutes or more) and their effects on nighttime sleep in a group of healthy young and middle-aged adults. The young and middle-aged adults reported very similar sleep and napping patterns, with approximately 74% of the participants in both groups reporting they had napped during a 7-day sleep-log period. Almost half of the participants reported that the average nap lasted less than 20 minutes. A multivariant analysis of variance (MANOVA) found no significant differences between the no-nap and the power-nap or long-nap groups in sleep quantity or quality for either age group. The current data suggested that power napping occurs frequently in healthy adults and that spontaneous napping does not negatively affect nighttime sleep. PMID- 11763828 TI - Biofeedback using telemedicine: clinical applications and case illustrations. AB - Telecommunications technology is dramatically changing our world, allowing healthcare professionals to offer medical healthcare, in the form of consultation, assessment, and treatment, through the use of new communications media. In behavioral medicine, advances in telecommunications have brought about new ways of offering services by expanding healthcare to patients located all over the world and simultaneously reducing costs and improving outcome efficacy. This article describes the use of biofeedback to treat various pain and psychophysiological disorders through telemedicine technology. The authors provide a description of "off-the-shelf," low-cost, and low-bandwidth telemedicine equipment used to deliver clinical biofeedback treatment when the patient and provider are in two different locations. In addition, the authors discuss practical issues of behavioral telehealth. PMID- 11763829 TI - Behavioral treatment of hypertensive heart disease in African Americans: rationale and design of a randomized controlled trial. AB - African Americans experience higher morbidity and mortality than Whites do as a result of hypertension and associated cardiovascular disease. Chronic psychosocial stress has been considered an important contributing factor to these high rates. The authors describe the rationale and design for a planned randomized controlled trial comparing Transcendental Meditation, a stress reduction technique, with lifestyle education in the treatment of hypertension and hypertensive heart disease in urban African Americans. They pretested 170 men and women aged 20 to 70 years over a 3-session baseline period, with posttests at 6 months. Outcomes included clinic and ambulatory blood pressure, quality of life, left ventricular mass measured by M-mode echocardiography, left ventricular diastolic function measured by Doppler, and carotid atherosclerosis measured by beta-mode ultrasound. This trial was designed to evaluate the hypothesis that a selected stress reduction technique is effective in reducing hypertension and hypertensive heart disease in African Americans. PMID- 11763830 TI - Proceedings from the 3rd International Congress of Paediatric Audiology. Copenhagen, Denmark, May 9-12, 2000. PMID- 11763831 TI - Obesity: Research and Clinical Practice, A Multidimensional Perspective. Saalbau, Essen, Germany. March 23-25, 2000. Proceedings and abstracts. PMID- 11763832 TI - Proceedings of the workshop on cytoreduction, stem cell mobilization and high dose therapy in relapsed/refractory malignant lymphomas. 12 October 2000, Hamburg, Germany. PMID- 11763833 TI - Re: "Nickelodeon in the new millennium". PMID- 11763834 TI - Nutrition and fitness: Diet, genes, physical activity and health. Proceedings of the 4th International Conference on Nutrition and Fitness. Athens, Greece, May 25 29, 2000. PMID- 11763835 TI - Nutrition and fitness: metabolic studies in health and disease. Proceedings of the 4th International Conference on Nutrition and Fitness. Athens, Greece, May 25 29, 2000. PMID- 11763837 TI - Expanding the prospects of nephrology in the Balkan Peninsula. Proceedings of the 5th Congress of the Balkan Cities Association for Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO). September 30-October 3, 2001. Thessaloniki, Greece. PMID- 11763836 TI - Women's work, health and quality of life: It is time we redefined women's work. Proceedings of the 11th International Congress on Women's Health Issues. San Francisco, California, USA. January 2000. PMID- 11763838 TI - Recent advance in sleep and chronobiology. Proceedings of a meeting. October 28 29, 2000. San Diego, California, USA. PMID- 11763839 TI - Bibliography. Current world literature. Nutraceutics and micronutrients. PMID- 11763840 TI - Bibliography. Current world literature. Nutrition and physiological function. PMID- 11763841 TI - Bibliography. Current world literature. Nutrition and the gastrointestinal tract. PMID- 11763842 TI - Russell of Russel's viper fame. PMID- 11763843 TI - [Integrated care in gastroenterology]. PMID- 11763845 TI - The new age of anti-terrorism. PMID- 11763844 TI - Responses to "A comparison of characteristics of Kevorkian euthanasia cases and physician-assisted suicides in Oregon". PMID- 11763846 TI - From the Centers for Disease Control and Prevention. Investigation of bioterrorism-related anthrax and adverse events from antimicrobial prophylaxis. PMID- 11763847 TI - From the Centers for Disease Control and Prevention. Considerations for distinguishing influenza-like illness from inhalational anthrax. PMID- 11763848 TI - From the Centers for Disease Control and Prevention. Interim guidelines for investigation of and response to Bacillus anthracis exposures. PMID- 11763849 TI - JAMA patient page. Anthrax. PMID- 11763850 TI - Christian (Chris) Neethling Barnard, 1922-2001. PMID- 11763851 TI - Abstracts from the 20th annual meeting of the European Underwater and Baromedical Society. Malta, 14-17 September 2000. PMID- 11763852 TI - HIV: future and futuristic therapies. PMID- 11763854 TI - From the Centers for Disease Control and Prevention. Investigation of bioterrorism-related anthrax, 2001. PMID- 11763853 TI - Ernst Schweninger, Professor of Dermatology, and Bismarck's personal physician. PMID- 11763855 TI - From the Centers for Disease Control and Prevention. Recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax. PMID- 11763856 TI - From the Centers for Disease Control and Prevention. Potential risk for lead exposure in dental offices. PMID- 11763857 TI - JAMA patient page. Youth violence in schools. PMID- 11763858 TI - [Central nervous system lesions in Adams-Oliver syndrome]. PMID- 11763859 TI - The effect of l-3,4-dihydroxyphenylalanine (= DOPA) on akinesia in parkinsonism. 1961. PMID- 11763860 TI - Variations in the concentration of radon in parts of the Ogof Ffynnon Ddu system, Penwyllt, South Wales and estimates of doses to recreational cavers. AB - A new winter and summer investigation of radon concentrations in parts of the Ogof Ffynnon Ddu system at Penwyllt, South Wales, has been carried out using 100 environmental National Radiological Protection Board track etch detectors. Fifty detectors were installed in the system in December 1998 and again in August 1999 for a period of a month. The data obtained confirm that the system has moderately high radon concentrations with a system mean of 2318 Bq m(-3) in winter and 2844 Bq m(-3) in summer. Traverse means have a summer high of 3094 Bq m(-3) for OFDI to Cwm Dwr and a winter low of 1946 Bq m(-3). The extremely high concentrations approaching 20,000 Bq m(-3), reported previously from the system (Hyland, 1995), have not been reproduced. The data show that the airflow directions at the entrances are not what might have been predicted. Air appears to be largely continuously emerging from the lowest entrance but, at the higher entrances, conversely to the predictions, in winter air enters and in summer appears to be coming out or is variable. Internally, there are sites that in winter have very low radon concentrations that can only be explained by the ingress of fresh air. These are not matched in the summer experiment, again indicating that ingress of fresh air to some parts of the system is very variable. The data illustrate the complexity of airflow within a multi-entrance system but behind these variations several mean concentrations can be obtained from which an approximation of the dose likely to be received can be calculated. Using the maximum mean concentration obtained, 3094 Bq m(-3), and using the latest dose conversion, a 10 h underground trip in the Ogof Ffynnon Ddu system yields a calculated dose of 0.12 mSv. Given that the recommended limit for a member of the public is 1 mSv, this dose would be reached after about 80 h of caving in the system. PMID- 11763861 TI - Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity. AB - Calcium phosphate cement (CPC) sets to form hydroxyapatite and has been used in medical and dental procedures. However, the brittleness and low strength of CPC prohibit its use in many stress-bearing locations, unsupported defects, or reconstruction of thin bones. Recent studies incorporated fibers into CPC to improve its strength. In the present study, a novel methodology was used to combine the reinforcement with macroporosity: large-diameter resorbable fibers were incorporated into CPC to provide short-term strength, then dissolved to create macropores suitable for bone ingrowth. Two types of resorbable fibers with 322 microm diameters were mixed with CPC to a fiber volume fraction of 25%. The set specimens were immersed in saline at 37 degrees C for 1, 7, 14, 28 and 56d, and were then tested in three-point flexure. SEM was used to examine crack-fiber interactions. CPC composite achieved a flexural strength 3 times, and work-of fracture (toughness) nearly 100 times, greater than unreinforced CPC. The strength and toughness were maintained for 2-4 weeks of immersion, depending on fiber dissolution rate. Macropores or channels were observed in CPC composite after fiber dissolution. In conclusion, incorporating large-diameter resorbable fibers can achieve the needed short-term strength and fracture resistance for CPC while tissue regeneration is occurring, then create macropores suitable for vascular ingrowth when the fibers are dissolved. The reinforcement mechanisms appeared to be crack bridging and fiber pullout, the mechanical properties of the CPC matrix also affected the composite properties. PMID- 11763862 TI - Superhydrophobic modification fails to improve the performance of small diameter expanded polytetrafluoroethylene vascular grafts. AB - To determine whether superhydrophobic modification of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts improves the performance of these grafts, we assessed neointima formation and platelet deposition in standard and superhydrophobic modified ePTFE grafts. Standard and superhydrophobic vascular grafts were implanted in the carotid arteries of two rabbits and two pigs. Furthermore, standard and superhydrophobic vascular patches were implanted in the carotid arteries of seven pigs. After 4 weeks of implantation all patches were removed and histomorphometric data were analyzed. The early thrombotic effect of superhydrophobic modification was examined by quantifying platelet glycoprotein receptor IIIa deposition onto each type of vascular graft after 15 min of in vitro circulation with human blood. All superhydrophobic and standard ePTFE vascular grafts occluded 15 min to 1 h after implantation in both rabbit and pig carotid arteries. All implanted patches remained patent and were completely covered by endothelium. Superhydrophobic modification of ePTFE vascular grafts did not lead to less neointima formation and resulted in significantly more platelet deposition than did standard ePTFE vascular grafts. Thus, superhydrophobic modification does not improve the performance of small diameter ePTFE vascular grafts. PMID- 11763863 TI - [Implementation of the European Union chemical safety regulation in Poland]. PMID- 11763864 TI - Origin of neck pain. Part 3. PMID- 11763865 TI - Perceived racism and self and system blame attribution: consequences for longevity. AB - In this article, we examine the National Survey of Black Americans to assess the relationship between perceived racism, self and system blaming attribution and survival. Perceived exposure to racism and other covariates were measured at baseline (1979) with a mortality follow up 13 years later (1992). We test the hypothesis that an external attributional orientation (which we refer to as system blaming) as opposed to an internal attributional orientation (which we refer to as self blaming) will be protective of health (as measured at 13-year survival) when individuals are exposed to racism. Using Cox proportional hazards regression modeling, we found support for our hypothesis. African Americans with a system-blaming orientation who reported experiencing racism were more likely to survive the 13-year follow-up period, compared to self blamers who did not perceive themselves to have been exposed to racism (OR = .37, CI95: .21, .64). Controlling for other known correlates of survival (age, health status at baseline, sex, marital status, smoking, and income) did not eliminate the significant effect of self-blame orientation among those exposed to racism (OR = .43, CI 95: .23, .82). The findings suggest that the attribution of negative events to external factors, such as systemic societal racism, rather than to individual characteristics, may be adaptive and protective of health status. PMID- 11763867 TI - Removal of fiber posts from endodontically treated teeth. AB - The removal of posts from endodontically treated teeth can be a major obstacle in the retreatment of teeth that have recurrent pathology, often leading to extraction of a tooth that could have been saved with endodontic retreatment. The use of a fiber post offers the advantages of a suitable elastic modulus and good bonding between post and cement, but also the advantage of easy removal, if so indicated by clinical findings. A special removal kit for fiber posts has been developed, and its use is illustrated, and described. The removal procedure can be completed in a very short time, usually less than 5 min. The tooth can then be restored with the same type and size of fiber post as was in the tooth prior to removal. Removal kits are found to be for single use only. PMID- 11763866 TI - Clinical evaluation of fiber-reinforced epoxy resin posts and cast post and cores. AB - PURPOSE: This retrospective study evaluated treatment outcome of cast post and core and Composipost systems after 4 yrs of clinical service. MATERIALS AND METHODS: 200 patients were included in the study. They were divided in two groups of 100 endodontically treated teeth restored with a post. Group 1: Composipost systems were luted into root canal following the manufacturer's instructions. Group 2: Cast post and cores were cemented into root canal preparations with a traditional technique. The patients were recalled after 6 months, 1, 2 and 4 yrs and clinical and radiographic examinations were completed. Endodontic and prosthodontic results were recorded. RESULTS: Group 1: 95% of the teeth restored with Composiposts showed clinical success; 3% of these samples were excluded for noncompliance and 2% showed endodontic failure. Group 2: Clinical success was found with 84% of teeth restored with cast post and core. 2% of these samples were excluded for noncompliance, 9% showed root fracture, 2% dislodgment of crown and 3% endodontic failure. Statistical evaluation showed significant differences between Groups 1 and 2 (P < 0.001). The results of this retrospective study indicated that the Composipost system was superior to the conventional cast post and core system after 4 yrs of clinical service. PMID- 11763868 TI - In vitro evaluation of endodontic posts. AB - PURPOSE: To compare stainless steel posts and three different fibrous posts with respect to pullout (shear) strength from extracted third molars embedded in denture acrylic. MATERIALS AND METHODS: Post space was prepared and the posts cemented with a resin cement according to manufacturer's instructions. Single step and multi-step dentin bonding systems were also evaluated. The testing was in tension at a loading rate of 2 mm/min. RESULTS: The statistical analysis indicated no significant difference in the pullout (shear) strength between any of the post groups tested. Also evaluated was the flexure strength of the fibrous posts before and after thermal cycling. Statistical analysis indicated a significant decrease in flexure strength for the respective fibrous posts following thermal cycling. PMID- 11763869 TI - Retrospective study of the clinical performance of fiber posts. AB - PURPOSE: To evaluate the clinical performance of C-Posts, AEstheti Posts and AEstheti Plus Posts after a period of clinical service ranging from 1-6 yrs. MATERIALS AND METHODS: 1,304 posts were included in the study: 840 Composiposts, 215 AEstheti posts and 249 AEstheti Plus posts were placed into endodontically treated teeth. Four combinations of bonding/luting materials were used. The patients were recalled every 6 months and clinical and radiographic examinations were completed. Endodontic and prosthodontic results were recorded. Actuarial Life Table statistical analysis and Mantel-Haenszel comparison of survival curve have been performed at 95% level of confidence. RESULTS: The 3.2% failure rate was due to two reasons: 25 posts debonded during removal of temporary restorations, and 16 teeth showed periapical lesions at the radiographic examination. No statistical significant differences were found among the four groups. The results of this retrospective study indicate that fiber posts in combination with bonding/luting materials can be routinely used. PMID- 11763871 TI - [The dismembered body: the social history of early modern anatomical section]. PMID- 11763870 TI - [The history of Italian psychology. Essay reviews of works by: Cimino G; Dazzi N.; 1998 and Albertazzi L; Cimino G; Gori-Savellini S., 1999]. PMID- 11763872 TI - From the dinner table to the state house. AB - A Tennessee lawmaker, moved by his wife's tales from her job as a school nurse, has taken a stand to improve school health programs. PMID- 11763873 TI - States respond to growing abuse of painkiller. AB - OxyContin has been touted as a "miracle" drug for its abilities to ease chronic pain. But a growing number of addicts are obtaining it illegally because of the immediate, intense "high" it gives them. PMID- 11763874 TI - [Sterility and fertility: the role of males]. PMID- 11763875 TI - A trust analysis of a gestational carrier's right to abortion. PMID- 11763876 TI - The severely to profoundly hearing impaired population in the United States: prevalence and demographics. PMID- 11763877 TI - The quality of life and economic implications of daily dialysis. PMID- 11763878 TI - The societal costs of severe to profound hearing loss in the United States. PMID- 11763879 TI - The Icelandic health sector database. PMID- 11763880 TI - Central health database in Iceland and patients' rights. PMID- 11763881 TI - Using existing data to track insurance and access to health care in California. PMID- 11763882 TI - The passions and animal language, 1540-1700. PMID- 11763883 TI - Hobbes on explanation and understanding. PMID- 11763884 TI - The use of postcards to advertise products sold by pharmacies in Britain. PMID- 11763885 TI - Social validation: an historian's look at complementary/alternative medicine. PMID- 11763886 TI - Frame food diet. PMID- 11763887 TI - John Dewey and early Chicago functionalism. AB - John Dewey and James Angell are regarded respectively as the founder and systematizer of the Chicago school of functional psychology. The early Chicago school traditionally has been portrayed as a unified theoretical approach based primarily on William James's naturalist theory of mental processes. It is argued in this article that although the psychology systematized by Angell bore a close affinity to James's naturalism, Dewey's own psychology was based primarily on the neo-Hegelian philosophy of Thomas Hill Green. Through a review of a number of Dewey's major writings, Green's neo-Hegelian philosophy is shown to have influenced Dewey's views on psychological concepts such as reaction, emotion, and perception during the formative period of the Chicago school. The interpretation of Dewey's psychology developed in this article leads to the conclusion that early Chicago functionalism should not be regarded as a unified theoretical approach. PMID- 11763888 TI - The repeated reproduction of Bartlett's Remembering. AB - There is a striking parallel between the treatment of F. C. Bartlett's theories of memory in the psychological literature and Bartlett's own characterization of reproductive memory as interest driven and constructive. Three periods of intensified interest in Bartlett's classic book Remembering (1932/1995) can be identified. The 1st occurred in the wake of the publication of Remembering and focused on replication and extension of the empirical work. The 2nd was during the period of the "cognitive revolution" and treated Bartlett's key theoretical concept of "schema" within an information-processing framework. The 3rd is an ongoing revitalization of interest in the cultural and social aspects of Bartlett's multifaceted theory. Each wave of increased interest in Bartlett's work has brought different aspects of his thinking to the fore, producing different versions of his theory of remembering that reflect the theoretical climate of the time. PMID- 11763889 TI - To be a big shot or to be shot: Zing-Yang Kuo's other career. AB - The radical behaviorist Zing-Yang Kuo's other career reveals a figure who moved in the circles of senior university administrators and significant political figures. When he left China for Hong Kong after World War II (WWII), he did no more scientific research but embarked on an autobiography and a study of Chinese national character. A chance renewal of his acquaintance with Leonard Carmichael led to the simultaneous publication of several articles based on work done in the 1930s, and thereby to the revival of Kuo's scientific reputation. However, Kuo preferred to pursue his national character studies--his only post-WWII funded work. The author argues that it was the failure of Kuo's ambitions in China that led to both his interest in national character and to the revival of his scientific reputation, which might otherwise have lain dormant. PMID- 11763890 TI - The international union of psychological science and the politics of membership: psychological associations in South Africa and the German Democratic Republic. AB - This article examines the origins and the development of psychological associations in the German Democratic Republic and the Republic of South Africa and the ways membership in the International Union of Psychological Science (IUPsyS)--founded in 1951--figured in the process. The political regimes in these 2 countries had difficulties of their own in achieving a standing in the international community and, as a result, psychologists faced significant dilemmas in gaining legitimacy for the discipline. Membership in the IUPsyS served an important function in gaining legitimacy for the discipline in both countries, but it also contradicted legitimizing strategies that involved the countries' distinctive political and social structures. Membership in the IUPsyS was sufficiently important for psychologists to try to strike a compromise between different legitimation strategies. PMID- 11763891 TI - A pro-life loss of nerve? PMID- 11763892 TI - One patent a day keeps the doctor away? Patenting human genetic information and health care. PMID- 11763893 TI - Regulations and organ transplantation in Turkey. AB - The concrete expression of ethical values in legal arrangements may require a long period. In our experience, this period can sometimes be quite brief when it comes to bioethical issues, as it can be seen in the legal arrangement in Turkey concerning organ transplantations. Turkey can be considered a fortunate country with respect to legal arrangements for organ transplantation in that laws on organ transplantation in Turkey date back to twenty years ago. At the time this law went into effect, the ethical discussion on this issue were yet to begin. The rationale behind the law was to prevent physicians from legal prosecution due to organ transplantation. Yet, the attempt to place organ transplantation into a certain legal framework alleviates our ethical concerns. PMID- 11763894 TI - Recommendation No. R (99) 4 of the Committee of Ministers to member states on principles concerning the legal protection of incapable adults, an introduction in particular to part V Interventions in the health field. PMID- 11763895 TI - [Medical ethics in the clinical context -- a new concept by the physician Richard C. Cabot]. AB - Richard C. Cabot was a professor of medicine and philosophy at Harvard University. He developed a very practical system of medical ethics structured by the hospital, its patients and care givers. Clearly he differentiated between a concept from an inside perspective and a concept born from an outside perspective. Thus, he opposed to the orientation to ethical codes which the American Medical Association established since 1847 (the outside perspective). The code-tradition was oriented by principles without professional context, while Cabot focused his concept of ethics rather on duty, which can not be reflected without its context (the inside perspective). This paper displays the essentials of his concept of ethics: 1) communication as the substantial core of medicine, 2) the basis in cases, 3) the multi/-interdisciplinarity, 4) the focus on the structure of therapy, i.e. care giving, 5) the respect of the patient, and 6) the obligation by truth. PMID- 11763896 TI - Effect of conditioning times on resin-modified glass-ionomer bonding. AB - PURPOSE: To evaluate in vitro the effect of different polyacrylic acid conditioning times on the shear bond strength of a resin-modified glass-ionomer bonded either to enamel to dentin surfaces. MATERIALS AND METHODS: 36 flat enamel and 36 dentin bond sites were prepared to 600 grit on human incisors. Five groups (n = 6 per group) for each substrate (enamel or dentin) were conditioned using 20% polyacrylic acid and 3% aluminum chloride for either 10, 20, 40, 80, or 160 s before bonding with the resin-modified glass-ionomer. A non-conditioning group per substrate group was used as a control. A hybrid composite was placed in two increments in a 3 mm diameter matrix on the treated surfaces. The specimens were stored for 4 weeks in distilled water at 37 degrees C. Shear bond strengths were determined using an Instron testing machine with a load rate of 0.5 mm/min. Additionally, 15 enamel and 15 dentin samples were tested with a profilometer to quantify changes in surface roughness during the different conditioning times. RESULTS: Dentin shear bond strength values were not significantly different among the different groups, including the unconditioned control group. For enamel, the unconditioned group was significantly weaker than any of the conditioned groups. No significant differences (P > 0.05) were found among the conditioned enamel specimens. No significant differences in surface roughness were found for either enamel or dentin. PMID- 11763897 TI - A comparison of the Braun Oral-B 3D plaque remover and the Sonicare plus electric toothbrush in removing naturally occurring extrinsic staining. AB - PURPOSE: To compare the extrinsic stain-removing properties and the safety of the Braun Oral-B 3D Plaque Remover and the Sonicare Plus electric toothbrush. MATERIALS AND METHODS: This randomized, parallel group, investigator-blinded study involved 67 subjects and was conducted over 6 weeks. After recruitment, the subjects received a baseline stain assessment (Lobene stain index) and a soft and hard tissue examination, and were then randomized to use either the Sonicare or the 3D device. All subjects were trained to use both devices, and instructed to brush twice daily with their assigned device for 2 min. The subjects' brushing technique was checked after 2 weeks. After a further 4 weeks, the subjects underwent a final stain assessment and soft and hard tissue examination. A questionnaire was also completed. RESULTS: At 6 weeks, oral hard and soft tissue examinations revealed no abrasion or damage in either group. Both brushes produced significant (P < 0.001) reductions from baseline in total stain score, stain area and intensity, but group comparisons showed that these reductions were significantly (P < 0.001) greater for the 3D device. PMID- 11763898 TI - Effect of dentin desensitizers and dentin bonding agents on dentin permeability. AB - PURPOSE: To determine the effect of dentin desensitizing agents (oxalates and glutaraldehyde) and dentin bonding agents, with and without resin-based composite (RBC) on dentin permeability and morphology of the dentin surface. The influence of saliva and toothbrushing on these agents was also evaluated. MATERIALS AND METHODS: Radicular dentin discs +/-1 mm thick were obtained from extracted human teeth. The thickness of the discs was standardized by grinding them with 600 grit silicon carbide powder. Both pulpal and periodontal surfaces of the discs were treated with 6% citric acid for 2 min prior to the baseline measurement of dentin permeability. Permeability was measured for the discs, using a split-chamber apparatus, at four different time points: at baseline, after treatment with each desensitizing modality, after 24 hrs of saliva immersion and after simulated toothbrushing equivalent to 3 weeks of normal brushing. The treatment modalities were: Sensodyne Dentin Desensitizer, Gluma Dentin Desensitizer, All-Bond DS (primers without etching), Etch+Primers (All-Bond 2 system), Etch+Primers+Adhesive and Etch+Primers+Adhesive+RBC (AElite Flo). Radicular dentin discs were prepared separately for scanning electron microscopy (SEM). One group was left untreated as the control group. Discs in the other groups were treated with the modalities listed above. One disc from each group was viewed under the SEM after treatment with the desensitizing modality. The second disc in each group was viewed after 24 hrs of saliva immersion following desensitizing treatment and the third disc after 3 weeks of simulated toothbrushing following desensitizing treatment and saliva immersion. RESULTS: The greatest reduction in permeability was caused by All-Bond DS followed by Sensodyne Dentin Desensitizer and Etch+Primers+Adhesive+RBC. Gluma Dentin Desensitizer, Etch+Primers, and Etch+Primers+Adhesive did not reduce permeability by a significant amount. Saliva immersion increased permeability significantly only for the Gluma and Etch+Primers+Adhesive groups. There was a trend towards increase in permeability after toothbrushing; however, this increase was not statistically significant for any group (P > 0.05). Thus, placement of primers without etching (All-Bond DS) reduced permeability more than any other treatment modality. These data indicate that etching a sensitive dentin area may be appropriate only if RBC is to be placed in the area. Exposure to saliva and toothbrushing countered the decrease in permeability caused by dedicated desensitizers and dentin bonding agents. The SEM micrographs revealed that in most cases, form corroborated function and the morphology of the dentin surface corresponded to the dentin permeability values. PMID- 11763899 TI - Biocompatibility of a resin-modified glass-ionomer cement applied as pulp capping in human teeth. AB - PURPOSE: to evaluate the human pulp response following pulp capping with calcium hydroxide (CH, Group 1), and the resin-modified glass-ionomer Vitrebond (VIT, Group 2). MATERIALS AND METHODS: Intact teeth with no cavity preparation were used as control Group (ICG, Group 3). Buccal Class V cavities were prepared in 34 sound human premolars. After exposing the pulps, the pulp capping materials were applied and the cavities were filled using Clearfil Liner Bond 2 bonding agent and Z100 resin-based composite. The teeth were extracted after 5, 30, and from 120 to 300 days, fixed in 10% buffered formalin solution, and prepared according to routine histological techniques. 6-microm sections were stained with hematoxylin and eosin, Masson's trichrome, or Brown & Brenn technique for bacterial observation. RESULTS: At 5 days, CH caused a large zone of coagulation necrosis. The mononuclear inflammatory reaction underneath the necrotic zone was slight to moderate. VIT caused a moderate to intense inflammatory pulp response with a large necrotic zone. A number of congested venules associated with plasma extravasation and neutrophilic infiltration was observed. Over time, only CH allowed pulp repair and complete dentin bridging around the pulp exposure site. VIT components displaced into the pulp tissue triggered a persistent inflammatory reaction which appeared to be associated with a lack of dentin bridge formation. After 30 days a few histological sections showed a number of bacteria on the lateral dentin walls. In these samples the pulp response was similar to those samples with no microleakage. VIT was more irritating to pulp tissue than CH, which allowed pulp repair associated with dentin bridge formation. These results suggested that VIT is not an appropriate dental material to be used in direct pulp capping for mechanically exposed human pulps. PMID- 11763900 TI - Morphological effects of surface treatments on ceramic restorative materials. AB - PURPOSE: To examine and evaluate the topographies of Vita Mark II and Dicor MGC surfaces by SEM after simulating the common clinical procedures. MATERIALS AND METHODS: Twelve (12) samples of Dicor MGC and 12 samples of Vita Mark II were milled on a Cerec, a computer-controlled machine. Three cut surfaces were observed and photographed using a scanning electron microscope following standardized milling, etching and polishing procedures. RESULTS: The surface topographies of the ceramic restorative materials showed distinctly different characteristics. Dicor MGC showed definite shaped crystals after etching. The surface characteristics of etched Dicor MGC were different than etched Vita Mark II, which exhibited large trabeculations. The occlusal and proximal surfaces, which were not etched but polished, displayed large vacuoles with Vita Mark II while smaller vacuoles were seen in the fused crystals of Dicor MGC. PMID- 11763901 TI - Cleaning dental instruments: measuring the effectiveness of an instrument washer/disinfector. AB - PURPOSE: To analyze the cleaning effectiveness of one type of instrument washer available for use in a dental office. MATERIALS AND METHODS: Dental instruments were heavily contaminated with blood and specific test bacteria. They were placed in cleaning baskets or within instrument cassettes, processed through the instrument washer, and analyzed for remaining blood and viable bacteria. RESULTS: Information obtained indicated that the washer is an effective cleaning system for dental instruments. PMID- 11763902 TI - Recent developments in dentin bonding. AB - Hybridization of the dentin with resin by monomer interdiffusion has been identified as the basic bonding mechanism resulting in an intimate interlocking of the cured resin with the dentin. Today, growing efforts are made to simplify and shorten the bonding procedures, e.g. by combining the functions of primer and adhesive. Ultrastructural investigations using high-resolution optical technology provided exciting insight into the interactions of bonding systems and dentin. It became clear, that the maintenance or recovery of microporosities in the dentin is most important for optimal hybridization. This can be achieved by the moist bonding technique, which is mandatory in acetone-based systems. The observation that certain bonding systems are able to bond to dentin depleted from the demineralized collagen network raised the question of whether the collagen-resin interdiffusion zone really represents a prerequisite for successful bonding to dentin. The use of strongly acidic primer monomers introduced the concept of "self-etching" primers not only to dentin but also to enamel, which eliminates the necessity of a separate conditioning step. Clinical investigations are necessary to evaluate the potential of recently developed all-in-one products which combine the functions of conditioner, primer, and adhesive. With improvements in dentin bonding and the development of new resins that exhibit little or no shrinkage upon polymerization, even greater applications for adhesive technology will be found in dentistry. PMID- 11763903 TI - Infection control in the new millennium. PMID- 11763904 TI - Lipoma of the buccal vestibule. PMID- 11763905 TI - Enamel color change by microabrasion and resin-based composite. AB - A simple technique using microabrasion with hydrochloric acid/pumice and resin based composite to improve the esthetics of discolored anterior teeth is described. PMID- 11763906 TI - Postadjustment polishing of CAD-CAM ceramic with luminescence diamond gel. AB - PURPOSES: (1) to investigate by SEM and profilometry the effectiveness of Luminescence diamond polishing gel on machinable ceramic after adjustment grinding with different grit diamond finishing burs, and (2) to define a simple, time-saving ceramic finishing and polishing technique for clinically satisfactory results. MATERIALS AND METHODS: Discs, 3 mm thick, were cut from Vita Mark II CAD CAM ceramic and ground to a uniform surface finish on 600 grit wet SiC paper. Five specimens in each of the seven groups below were finished unidirectionally by a sweeping mode with the following Two Striper MFS diamond burs: 1. MF1 (45 microm); 2. MF2 (25 microm); 3. MF3 (10 microm); 4. MF1 + MF2; 5. MF1 + MF3; 6. MF2 + MF3; 7. MF1 + MF2 + MF3. Then, Luminescence diamond polishing gel was dispensed on a mandrel-mounted felt applicator and applied at 10,000 rpm for 60 s, and after dipping in water for another 60-s sequence. Surface roughness was determined for each step with a stylus-fitted surface analyzer. On each specimen five parallel tracings (evaluation length 4.0 mm and cut-off length 0.8 mm) were made 1 mm apart. Ra and Rz values were recorded as roughness parameters. Data was subjected to one-way ANOVA and Tukey's multiple comparison test at a significance level of alpha = 0.05. One additional sample for each grinding and polishing step in each of the seven groups was produced for SEM analysis. RESULTS: Diamond polishing after MF1 finishing reduced Ra and Rz significantly from 1.75 to 0.79, and from 10.0 to 4.09 microm, respectively, whereas the Ra and Rz reduction after MF3 finishing and diamond polishing were from 0.64 to 0.49 and from 4.31 to 1.81 microm. The polished surface roughness of specimens prefinished with MF2 or MF3 burs alone or as the final step after preceding grinding with coarser grits was not significantly different. The average Ra and Rz values were 0.42 microm and 1.73 microm. SEM photographs confirmed the uniformity of the surface finish in these groups. The second polishing sequence did not significantly improve the smoothness obtained with the first cycle. PMID- 11763907 TI - Anticalculus effect of two zinc citrate/essential oil-containing dentifrices. AB - PURPOSE: To assess the feasibility of incorporating zinc citrate, a known anticalculus ingredient, into a dentifrice formulation containing a fixed combination of essential oils, a known antiplaque/antigingivitis agent. MATERIALS AND METHODS: This randomized, parallel, double-blind study evaluated the potential of two essential oil dentifrice formulations containing different levels of zinc citrate (1.0% and 2.0% ZCT) to reduce supragingival calculus formation compared to a marketed control dentifrice, Crest Regular. Following a 3 month pre-test phase, subjects received a dental prophylaxis, were stratified into three balanced groups on the basis of Volpe-Manhold calculus scores and brushed twice daily with their assigned dentifrice for 3 months. RESULTS: One hundred ninety-six evaluable subjects completed all phases of the study. ANCOVA revealed that the 1.0% ZCT and 2.0% ZCT essential oil dentifrice formulations provided significant reductions in calculus formation of 26.4% and 29.0% (P< 0.001), respectively, compared to the control dentifrice, Crest Regular. The magnitude of calculus reductions is similar to those levels obtained by other zinc salt formulations. PMID- 11763908 TI - Caries inhibition efficacy of an antiplaque/antigingivitis dentifrice. AB - PURPOSE: To evaluate the efficacy of a fluoride dentifrice containing a fixed combination of essential oils (Thymol, Menthol, Eucalyptol, and Methyl Salicylate) in preventing caries in Sprague Dawley rats. MATERIALS AND METHODS: The dentifrice contains 0.76% sodium monofluorophosphate (SMFP) as the fluoride source and a silica abrasive system. A fluoride-free placebo and a clinically proven USP dentifrice reference standard for SMFP/silica were included as controls. Three groups of 45 SDV-free Sprague Dawley weanlings were infected by a cariogenic strain of Streptococcus sobrinus and fed cariogenic diet NIH 2000 ad libitum. Animals were treated twice daily (once on weekends) with the assigned dentifrice using a cotton-tipped applicator, for 5 wks, after which they were terminated and caries scored using Larson's modification of the Keyes method. RESULTS: Analyses of variance were used to compare inter-group means, the total E lesion score was the primary efficacy variable. Compared with the fluoride-free vehicle control, the experimental dentifrice and USP reference standard dentifrice produced a statistically significant reductions of 18.3% and 12.2% respectively for total caries score (P<0.001). Compared with the clinically tested USP positive control dentifrice, the experimental dentifrice produced a statistically significant reduction in the total caries score of 6.9% (P=0.028). The results of this study show that 1) both the new dentifrice containing essential oils and USP dentifrice are statistically significantly effective in reducing caries in the rat model, 2) the anticaries activity of the SMFP dentifrice is not adversely affected with the addition of essential oils. PMID- 11763909 TI - Clinical effectiveness of essential oil-containing dentifrices in controlling oral malodor. AB - PURPOSE: To assess the efficacy of two essential oil-containing dentifrices in the reduction of human intrinsic oral malodor ("morning bad breath"). MATERIALS AND METHODS: Two clinical trials were conducted which used observer-blind, negative control, parallel designs. To insure a homogeneous test population with similar oral odor characteristics, subjects followed instructions that included toothbrushing with a standard ADA-accepted fluoride dentifrice the night before. On odor evaluation days, subjects refrained from all oral hygiene procedures and from eating or drinking any food or beverage or smoking prior to and during the odor evaluations. Eighty healthy adult subjects in the first trial and 90 in the second trial with qualifying baseline levels of oral malodor participated. Odor ratings of each subject's breath were made by 4-5 trained judges using a nine point hedonic scale, i.e., 1 = most pleasant, 5 = neutral, 9 = most unpleasant. Qualifying subjects were randomly assigned one of two essential oil dentifrices or a negative control dentifrice. Subjects brushed with their assigned dentifrice for 60 s, rinsed with 20 ml of water for 10 s, and received post-treatment hedonic odor ratings at 30, 60, 90, 120, 180, and 240 min. Data were analyzed using an ANCOVA to adjust for baseline scores. RESULTS: The essential oil dentifrices were significantly more effective (P < or = 0.033) than the control in reducing intrinsic oral malodor from 90 to 120 min. PMID- 11763910 TI - Stain removal efficacy of two new fluoride dentifrices containing essential oils. AB - PURPOSE: To assess in vitro the stain removal efficacy of two new antiplaque/antigingivitis dentifrices utilizing a modification of a previously validated Stookey method. MATERIALS AND METHODS: The modifications to the original Stookey method are the following: (1) study design; three 5 x 5 Latin Squares were employed to minimize bias stemming from position or test run in the study. (2) statistical success criteria; a test formulation was judged to be effective if the lower one-sided 95% confidence limit was "equal to or higher than" 50 since a minimum PCR (pellicle cleaning ratio) score of 50 is needed for a dentifrice to show clinical efficacy. The two test dentifrice formulations contained a fluoride source, a silica abrasive system, and four essential oils. The ADA reference abrasive material (calcium pyrophosphate) and placebo toothpaste were included as positive and negative controls, respectively. RESULTS: Compared to the negative control, the positive control exhibited a statistically higher PCR score; therefore, the validity of this modified Stookey method was confirmed. Additionally, the lower limits of the one-sided 95% confidence interval for the two dentifrice formulations were above the threshold PCR of 50; therefore, this modified Stookey method should predict that both essential oil-containing dentifrices possess acceptable stain removal power. PMID- 11763911 TI - Effect of an essential oil-containing dentifrice on dental plaque microbial composition. AB - PURPOSE: To determine the effect of 6 months use of an essential oil-containing (EO) antiplaque/antigingivitis fluoride dentifrice on the balance of the oral microbial flora and on the emergence of resistant microbial forms by analysis of dental plaque and saliva. MATERIALS AND METHODS: The dentifrice essential oils consisted of a fixed combination of thymol, menthol, methyl salicylate, and eucalyptol. An identical fluoride-containing dentifrice without the essential oils served as the control. A subgroup of 66 subjects from a clinical trial population of 321 was randomly selected for characterization of their dental plaque microflora. Saliva was also cultured to monitor for the emergence of opportunistic pathogens. Supragingival plaque and saliva were harvested at baseline, after which subjects received a dental prophylaxis. Subjects were sampled again after 3 and 6 months of product use prior to clinical examination. Plaque was characterized for microbial content by phase contrast microscopy for recognizable cellular morphotypes and by cultivation on nonselective and selective culture media. Determination of the minimum inhibitory concentrations of the test agent against selected Actinomyces and Veillonella isolated bacterial species was conducted at all time points to monitor for the potential development of bacterial resistance. RESULTS: There were no statistically significant differences between the microbial flora obtained from subjects using the essential oil-containing dentifrice and the vehicle control for all parameters and time periods except for the percentage of spirochetes at 6 months and for percentage of "other" microorganisms at 3 months. The EO group exhibited a lower adjusted mean for both parameters. Additionally, there was no evidence of the development of bacterial resistance to the antimicrobial activity of the essential oils or the emergence of opportunistic pathogens. PMID- 11763912 TI - Essential oils in an antiplaque and antigingivitis dentifrice: a 6-month study. AB - PURPOSE: To determine if a dentifrice formulated with the fixed combination of essential oils possessed antiplaque and antigingivitis properties. MATERIALS AND METHODS: This study was a blinded, randomized, controlled clinical trial. The 6 month study had clinical examinations at baseline, 3 and 6 months. The examinations consisted of three indices; a plaque index, the Modified Gingival Index and a bleeding index. RESULTS: At 6 months, the essential oil-containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean plaque index scores exhibiting mean reductions of 18.3% and 18.1% relative to the vehicle control. At 6 months, the essential oil containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean gingival index scores compared to the vehicle control with reductions of 16.2% and 15.5%, respectively. Finally, for the gingival bleeding index, the essential oil-containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean bleeding index scores and reductions of 40.5% and 46.9% at 6 months compared to the vehicle control. PMID- 11763913 TI - Confocal and multi-photon microscopy of dental hard tissues and biomaterials. AB - Confocal microscopy is a technique that can be used both in the clinic and the high-resolution microscopy suite. This form of optical microscopy enables high resolution images to be made of samples with minimum requirements for specimen preparation. Images may be made of either reflections from the sample surface or, if an immersion medium is used to optically couple the objective lens, then sub surface images can be produced of reflective or fluorescent structures within semi transparent materials such as cells and dental hard tissues. These images are like optical sections, giving thin (> 0.35 microm) slices up to 200 microm below the surface of a mineralized tissue. The technique generates significant improvements in resolution, lying somewhere between that of conventional light microscopy and TEM/SEM. Instruments that work at video-rate allow high-speed events to be examined, such as in vivo clinical studies, cutting of dental tissues and fracture of adhesive interfaces. New dyes offer many exciting prospects for labeling changes in chemical composition in materials or biological tissues, while new imaging techniques such as multi-photon laser excitation of dyes give the potential of greater depth penetration and improved resolution. As with all new techniques the inexperienced should be aware of some of the artifacts inherent to the system. However, the widespread availability of conventional confocal microscopes should give ample opportunity for dental researchers to capitalize on this new technology. PMID- 11763915 TI - Focused ion beam in dental research. AB - Focused ion beam (FIB) has been available for over 10 yrs but until recently its usage has been confined to the semiconductor industry. It has been developed as an important tool in defect analysis, circuit modification and recently transmission electron microscope sample preparation. This paper introduces FIB and demonstrates its application in dental research. Its ion and electron imaging modes complement the SEM while its ability to prepare TEM samples from a wide range of material will allow the study of new types of adhesive interface. As an example, its use is described in the characterization of the interface of resin to a tribochemically treated surface of an experimental fiber-reinforced resin based composite. As with all new techniques, the initial learning curve was difficult to manage. This new instrument offers opportunities to expand research in dental materials to areas not possible before. PMID- 11763914 TI - New trends in dentin/enamel adhesion. AB - The acid-etch-technique has provided an ideal surface for bonding to enamel by using 30-40% phosphoric acid. The resulting etch pattern is characterized by the profuse formation of microporosities which allow the penetration of monomers into those porosities to form resin tags that provide micromechanical retention. Successful attempts of bonding to dentin in a similar fashion have been reported more recently. Due to the specific properties of dentin, such as its tubular structure and its intrinsic wetness, bonding to dentin has not yet reached the ideal characteristics. In spite of the existing deficiencies in dentin adhesion, the increasing demand for esthetic restorations has generated intensive research on new esthetic materials with special focus on amalgam alternatives. The bonding mechanism of recent dentin bonding agents is based on the penetration of ambiphilic molecules into acid-etched dentin to form a lacework of dentin collagen and polymerized monomers. Dentin adhesive systems that contain a multitude of different bottles of different colors and shapes belong to the past. Because clinicians are increasingly eager to try new materials, the actual tendency calls for simplification of the bonding procedure e.g. one-bottle adhesive systems and all-in-one no-bottle materials. In spite of simpler materials, a separate etching step is still needed for one-bottle systems. Nevertheless, manufacturers of these simplified one-bottle materials recommend their use to bond polyacid-modified composites (compomers) without a separate etching step. The most recent addition to the group of simplified adhesives is the all-in-one no-bottle adhesives; one of these all-in-one systems, Prompt L-Pop (ESPE) has resulted in very promising laboratory results when used on enamel. In spite of the uncertainty about the capacity of all-in-one adhesives to etch enamel adequately in vivo, scanning electron microscopy studies have resulted in an enamel-etching pattern morphologically similar to that corresponding to phosphoric acid-etched enamel. While all-in-one adhesive systems have been reported to result in very satisfactory dentin bond strengths, results from other laboratories suggest that bonding to dentin with all-in-one adhesive systems will need to be somewhat improved. Clinical studies, which are the ultimate test for the acceptance of dentin adhesives, are now underway in several centers. Six month data showed a very good clinical performance for this ultra-simplified all in-one adhesive system. PMID- 11763916 TI - Direct and indirect adhesive restorative materials: a review. AB - Esthetic restorative materials require a bonding procedure in order to be durable and reliable. In order to accomplish this ideal, the bonding system must be biocompatible, bond indifferently to enamel and dentin, have sufficient strength to resist masticator forces, have mechanical properties close to those of tooth structures, be resistant to degradation in the oral environment and easy to use. This paper reviews the published literature on direct and indirect adhesive restorative materials. PMID- 11763917 TI - Microscopy investigations. Techniques, results, limitations. AB - This paper critically reviews current microscopy techniques that are used to image resin-dentin interfaces and more in particular to investigate the process of hybridization and resin-tag formation. A short description of the four most commonly used microscopy techniques with their necessary specimen-preparation methodology is provided along with a discussion of their possibilities, limitations and potential artifact formation. With this critical appraisal on microscopy techniques available to study adhesive interfaces, it is hoped to encourage the use of high-resolution analytical tools to further elucidate the mechanisms of bonding at the ultra-structural level. Besides ultra-morphologic characterization, more research should be devoted to study the chemical and physical properties of resin-dentin bonds. The final objective of such fundamental research should be to establish a more durable and reliable adhesive restorative technique. PMID- 11763918 TI - Clinical results and new developments of direct posterior restorations. AB - PURPOSE: To (1) review the literature and analyze the longevity and reasons for failure of direct resin-based composite (RBC), amalgam, and glass-ionomer cement (GIC) restorations in stress-bearing posterior cavities and (2) to assess new material developments and treatment techniques to restore these cavities. MATERIALS AND METHODS: This work reviewed the dental literature predominately of the last decade for longitudinal, controlled clinical studies and retrospective cross-sectional studies. Only studies investigating the clinical performance of restorations in permanent teeth were included. Annual failure rates of direct resin-based composite, amalgam, and GIC restorations were determined and failure reasons were discussed. RESULTS: Annual failure rates in posterior stress-bearing cavities were determined to be: 0-9% for direct RBC restorations, 0-7% for amalgam restorations, and 1.9-14.4% for GIC restorations. The median annual failure rate of longitudinal studies for amalgam was calculated with 1.1%, for RBCs 2.1% and for GICs 7.7%. GIC is significantly worse compared with amalgam and RBC. Main reasons for failure were secondary caries, marginal deficiencies, fracture, and wear. Longitudinal studies showed a strong trend towards a higher longevity compared with cross-sectional investigations. PMID- 11763919 TI - A direct approach to restore anterior teeth. AB - When selecting the correct treatment for a patient with anterior esthetic problems, the dentist must choose between direct and indirect procedures. With situations allowing conservative treatment, direct resin restoration should be given strong consideration. Advances in materials and techniques that can positively affect this choice include pre-restorative bleaching procedures, new bonding agents, and new highly esthetic direct resin systems. A procedure is described to maximize esthetics and minimize finishing time during direct resin placement. PMID- 11763920 TI - Adhesive luting of indirect restorations. AB - PURPOSE: To describe the potential of adhesive luting procedures with respect to (1) material characteristics and classifications, (2) film thickness, (3) overhang control, (4) bonding to different inlay materials, (5) adhesion to tooth substrates and the problem of hypersensitivities, (6) wear of luting composites, and (7) clinical performance. MATERIALS AND METHODS: A literature review of relevant studies of various in vitro and in vivo studies enables an overview of possibilities and limitations of adhesively luted indirect restorations. RESULTS: (1) Resin-based composites are the material of choice for adhesive luting. Both material properties and wear behavior of fine particle hybrid-type resin-based composites are superior to other materials. The use of compomers is questionable due to hygroscopic expansion and possible crack formation as proven for IPS Empress caps in vitro and in vivo. (2) Recent luting cements exhibit excellent flow characteristics with mean film thicknesses ranging between 8 microm and 21 microm. The ultrasonic insertion technique is recommended for viscous luting composites or conventional restorative composites utilizing their thixotropic properties. (3) For successful overhang control, good fit of the restoration (during luting) and high radiopacity of the cement (after luting) are indispensable. Overhang control is estimated easier when the ultrasonic insertion technique is applied. (4) The pre-treatments of ceramic inlays using hydrofluoric acid or silica coating result in effective bonding; for pre-treatment of resin based composite inlays, silica coating is promising as well. (5) Bonding to enamel and dentin is proven clinically acceptable, but it should be performed with multi-step systems providing separate primers and bonding agents producing a perfect internal seal with almost no hypersensitivities. Dual-cured multi-step bonding agents provide the most promising potential. (6) The viscosity and filler content of the resin composite used for luting does not influence the wear characteristics within the marginal luting area in vivo. However, the ultrasonic insertion technique involving high viscosity materials provides enhanced handling characteristics for luting of tooth-colored inlays. (7) Clinical results with tooth-colored inlays and veneers are promising over periods of up to 10 yrs, including use in severely destroyed teeth. PMID- 11763921 TI - Advances in light curing. AB - PURPOSE: To review and connect the scientific background of light curing with clinical requirements and new technical opportunities in order to conclude the best technology for next generation light curing units. RESULTS: Three conclusions are drawn for proper light curing: (1) A minimum dose of light is needed (wavelength dependent); (2) Internal stress can be reduced by giving the sample time to flow before gel point is reached; (3) An upper intensity limit has to be respected to limit temperature increase as well as light intensity dependent deactivation of activated photoinitiators. These conclusions can best be realized by using the softstart approach. A comparison of different light generation technologies shows that LEDs are most likely to shape the next generations of curing lights. Due to their superior power conversion rate as well as to their optimum spectral emission small and handy devices can be realized that work battery-powered and totally silent. The benefits for the dentist are improved reliability, handling, and hygiene. PMID- 11763922 TI - Exploring beyond methacrylates. AB - PURPOSE: This article focuses on the polymerization shrinkage of current dental composites as their major disadvantage and to find new routes for a solution. MATERIALS AND METHODS: A brief introduction describes selected methods for the shrinkage determination as well as some principal solutions to overcome the shrinkage problem. RESULTS: Siloranes, a new class of ring opening monomers, are presented as a promising resin matrix for dental composites. The synthesis of these monomers, and further consequences of the new chemistry for the formulation are discussed. Two selected silorane composites are presented with their mechanical data and their volume shrinkage. PMID- 11763923 TI - Creating a reliable bond. An all-in-one system. AB - This paper explains the reasons why a new adhesion concept was developed, how it was conceived and what properties and test results were achieved with the product Prompt L-Pop that follows this new concept. Therefore, a short historical introduction into the development of adhesive materials is given followed by a summary of today's state-of-the-art techniques. The requirements for the new adhesion concept are pointed out and the outcome of the effort in the development is explained in more detail. In vitro and in vivo test results of Prompt L-Pop support the new concept by revealing excellent bond strength values in combination with good marginal adaptation and a significantly reduced post operative sensitivity. Finally, further developments regarding the new concept are discussed, such as the use of Prompt L-Pop in combination with plasma curing lights or indirect restorations. PMID- 11763924 TI - Clinical evaluation of an adhesive used as a fissure sealant. AB - PURPOSE: To compare the retention of a multi-use bonding agent (OptiBond) to a conventional sealant (Delton) used as pit and fissure sealants. MATERIALS AND METHODS: An informed consent was obtained from 38 subjects aged 11-17 yrs. Delton, a self-cured sealant, was applied to 86 teeth, and OptiBond, a dual-cure glass filled adhesive, was applied to 85 teeth, under cotton roll isolation and saliva ejector. Each subject received both sealing materials, randomly assigned to the sides of the mouth. The sealed teeth were followed up to 30 months. Clinical evaluation was performed by two examiners and the retention was classified as failure or success. RESULTS: Statistical analysis based on a stratified Cox proportional hazards regression model indicated that OptiBond had better clinical performance than Delton (P < 0.001). PMID- 11763925 TI - Effect of light source position and bevel placement on facial margin adaptation of resin-based composite restorations. AB - PURPOSE: To evaluate the effect of direction of first cure and the presence or absence of a facial margin bevel on the adaptation of facial margins of Class III resin-based composite (RBC) restorations. MATERIALS AND METHODS: Custom polyvinyl siloxane (PVS) light shields were fabricated for both the mesial and distal surfaces of 20 extracted incisors. Class III cavities were prepared in the mesial and distal surfaces of the incisors. On the facial, lingual, and gingival margins of 20 of the preparations a 0.5 mm wide enamel bevel was placed. The lingual and gingival, but not the facial, margins were beveled on the other 20 preparations. The PVS light shield was adapted to the tooth and trimmed to allow 1-2 mm of the facial margin to be exposed on 10 of the beveled and 10 of the non-beveled preparations. For the remaining 20 preparations the PVS light shield was trimmed to allow access of the curing light only from the lingual. Teeth were restored with Prisma TPH RBC. Using the appropriate shield, restorations in the facial first cure group were cured first from the facial and then from the lingual. Restorations in the lingual first cure group were cured only from the lingual. Restorations were finished flush with enamel margins and thermocycled following storage. Samples were exposed to a 50% solution of silver nitrate followed by light exposure. Teeth were sectioned and microleakage was evaluated at three levels (incisal, middle, and cervical). Four evaluators (blinded to direction of cure) independently scored microleakage using a categorical evaluation scale. Statistical analysis included non-parametric descriptive statistics, Cohen's kappa, chi-square analysis, and Kruskal-Wallis ANOVA. RESULTS: Samples prepared without a facial bevel revealed significantly more (P = 0.01) microleakage than preparations with a facial bevel. At the most incisal level, restorations cured first from the facial revealed significantly more (P < 0.001) microleakage than restorations cured first from the lingual. At the middle and cervical levels, restorations cured first from the facial revealed significantly less (P < 0.001) microleakage than restorations cured first from the lingual. When a facial bevel was present, samples cured first from the facial showed significantly less (P < 0.001) microleakage than those cured only from the lingual. PMID- 11763926 TI - Effect of stepped light exposure on the volumetric polymerization shrinkage and bulk modulus of dental composites and an unfilled resin. AB - PURPOSE: To compare the volumetric polymerization shrinkage and dynamic bulk modulus of five resins and an experimental unfilled resin polymerized with a stepped power light and with a conventional one step curing light. MATERIALS AND METHODS: Parallel sided glass rings 5 mm in diameter and 2 mm high were etched for 5 min with hydrofluoric acid and silanated. The density and volume of the rings were calculated before they were filled with either SureFil, AEliteflo, Pertac II, Z100, or an experimental unfilled resin. When cured, the resin was bonded to the glass ring which produced a mold with a configuration C-factor of approximately 0.8. The resin was cured for 40 s on each side using either a one step curing light or a stepped power curing light. After curing, the specimens were weighed in air and in water to calculate their final density and volumetric shrinkage. Ten samples were made using each light system and for each resin (total of 100 samples). The bulk modulus was determined for each resin using an ultrasonic method, and the percentage filler contents were determined by thermogravimetric analysis. RESULTS: The mean +/- SD volumetric polymerization shrinkage values ranged from 3.10 +/- 1.19% for SureFil using the one step light to 12.35 +/- 1.38% for the unfilled resin using the stepped power curing light. Student-Newman-Keuls post hoc test separated the 10 different materials into three significant groups at P= 0.05. The unfilled resin exhibited the highest volumetric shrinkage followed by the flowable composite (AEliteflo). For all materials tested, there was no significant difference in the volumetric shrinkage values when the resin was cured with the one step or the stepped power curing light. There was no significant difference in the volumetric shrinkage values for the hybrid composites (Pertac II, Z100, and SureFil). The volumetric shrinkage values were highly sensitive to filler weight (P < 0.001). Except for Z100, there was no difference in the specific gravity values and velocities of the longitudinal and shear waves and bulk modulus when the one step and stepped power curing lights were used. The bulk modulus values ranged from 6.30 +/- 0.19 GPa for unfilled resin, to 17.10 +/- 1.09 GPa for Z100. Curing with the one step or the stepped curing light had no significant effect on the modulus values for any resin with the exception of Z100, P = 0.05. The bulk modulus values were highly sensitive to filler weight, and higher modulus values were associated with increased filler weight (P < 0.001). There was no significant difference between the bulk modulus of Pertac II and SureFil (P = 0.05). PMID- 11763927 TI - Bond strength of brackets cemented with light-cured glass-ionomer cements to contaminated enamel. AB - PURPOSE: To examine the effect of contamination on the bond strength of orthodontic brackets cemented with either a commercial (Fuji Ortho LC) or an experimental light-cured glass-ionomer cement to enamel, and the effect of etching times on the bond strength. MATERIALS & METHODS: Simulated metal brackets were applied with the cements to bond polished and etched (37% phosphoric acid) bovine enamel with and without contamination by water, human saliva, and blood. After 1-day water immersion, the shear bond strengths were measured. The fractured surfaces were examined using SEM. Additional tests were conducted on: (1) the Knoop hardness of the contaminated cements, (2) the HEMA composition of the cements, (3) the viscosity of the cements, and (4) the intensity of transmitted visible light through the contaminants. The results were compared by ANOVA and Duncan's tests at P=0.05. RESULTS: Water and saliva reduced the bond strength to polished and etched enamel, except for the bond strength of Fuji Ortho LC to polished enamel. The blood contamination produced poor bond strengths to polished and etched enamel. The experimental cement showed higher bond strengths to polished enamel with water and saliva contamination than Fuji Ortho LC. The bond strength of the experimental cement to etched enamel with and without contamination were comparable to those of Fuji Ortho LC. SEM micrographs revealed that the specimens exhibiting high bond strengths to polished and etched enamel mainly had cement-enamel interface failure and cement-metal mesh interface failure, respectively. Fuji Ortho LC had higher HEMA concentration than the experimental cement. The highest viscosity was measured with blood, followed by saliva and water. Blood contamination, showing the highest attenuation of the light intensity, reduced Knoop hardness of the experimental cement and Fuji Ortho LC. PMID- 11763928 TI - Use of one-bottle adhesive as an intermediate bonding layer to reduce sealant microleakage on saliva-contaminated enamel. AB - PURPOSE: To evaluate the influence of three different adhesives, each used as an intermediary layer, on microleakage of sealants applied under condition of salivary contamination. MATERIALS AND METHODS: Six different experimental conditions were compared, 3 with adhesives and 3 without. After prophylaxis and acid etching of enamel, salivary contamination was placed for 10 s. In Group SC the sealant was applied after saliva without bonding agent and then light-cured. In Group SCA, after saliva, the surface was air dried, and then the sealant was applied and cured. In Groups ScB, SB and PB, a bonding agent (Scotchbond Dual Cure/3M, Single Bond/3M and Prime & Bond 2.1/Dentsply, respectively) was applied after the saliva and prior to the sealant application and curing. After storage in distilled water at 37 degrees C for 24 hrs, the teeth were submitted to 500 thermal cycles (5 degrees C and 55 degrees C), and silver nitrate was used as a leakage tracer. Leakage data were collected on cross sections as percentage of total enamel-sealant interface length. Representative samples were evaluated under SEM. RESULTS: Sealants placed on contaminated enamel with no bonding agent showed extensive microleakage (94.27% in SC; 42.65% in SCA). The SEM revealed gaps as wide as 20 microm in areas where silver nitrate leakage could be visualized. In contrast, all bonding agent groups showed leakage less than 6.9%. Placement of sealant with a dentin-bonding agent on contaminated enamel significantly reduced microleakage (P < 0.0001). The use of a bonding agent as an intermediary layer between enamel and sealant significantly reduced saliva's effect on sealant microleakage. PMID- 11763929 TI - Cavity wall adaptation of resin-based composites lined with flowable composites. AB - PURPOSE: To compare the adhesion of a flowable resin-based composite (RBC) vs. a condensable RBC to tooth structure using scanning electron microscopy (SEM). MATERIALS AND METHODS: Fifteen recently extracted human teeth were prepared for Class I restorations and equally divided into three groups. Group 1 was filled with Heliomolar bonded with Syntac Single Component. Group 2 was lined with Flow It in addition to ALERT condensable RBC bonded with Bond-1 Primer/Adhesive. Group 3 was filled with ALERT bonded with Bond-1 Primer/Adhesive. All teeth were thermocycled, sectioned and evaluated for gap formation with the SEM. RESULTS: SEM at x15 demonstrated that restorations with the flowable RBC at the tooth/restoration interface showed no evidence of marginal gaps between the RBC material or at the underlying tooth structure. A significant difference (P < 0.05) in wall adaptation was found between Groups 2 and 3. PMID- 11763930 TI - Self-contamination of deep dentin by dentin fluid. AB - PURPOSE: To compare, with the use of a resin replica technique, surface features of deep, acid-conditioned dentin from vital human molars that were anesthetized with an anesthetic: Group 1: without a vasoconstrictor (Mepivacaine 3%), and Group 2: containing a vasoconstrictor (Lidocaine 2% with 1:80,000 epinephrine). MATERIALS AND METHODS: 10 Class I cavities with dentin caries were included in each group. Following complete caries removal, a total-etch technique was performed with 32% phosphoric acid (Uni-Etch) for 15 s. After rinsing, each cavity was air-dried for 1 s, then a slow setting vinyl polysiloxane (President) impression was taken. As a control, impressions were taken from three additional cavities in teeth that were anesthetized with Mepivacaine 3% but not acid etched. A TEM-grade epoxy resin was used to prepare replicas from the impressions. Polymerized replicas were coated with gold and examined with a scanning electron microscope. RESULTS: In Group 1, fluid was visible leaving tubular orifices in all replicas. In addition, three were covered with a smooth, amorphous film that was different from the granular appearance of the smear layer in the control cavities. In Group 2, patent tubular orifices without fluid were observed in all specimens. Odontoblast process-like structures were seen from some dentin tubules. PMID- 11763931 TI - Fluoride release/uptake from newer glass-ionomer cements used with the ART approach. AB - PURPOSE: To determine the fluoride ion release/uptake of two conventional glass ionomer cements (GICs) manufactured for use with the ART approach (Fuji IX GP, Ketac-Molar), as compared with that of a resin-modified GIC (Fuji II LC). MATERIALS AND METHODS: 15 specimens of each material were prepared and placed in vials with artificial saliva and stored at 37 degrees C. The solution was replaced weekly for 6 wks, and the fluoride ions released were measured in ppm each week. After 6 wks, the 15 specimens of each material were divided into three equal groups and placed into three fluoride recharging agents (1.23% APF gel, 1.1% neutral NaF and 0.001% CaF2) for 4 min at 23 degrees C. Fluoride ion measurements of the recharged specimens were carried out at 1 day, 2 days, then weekly for another 6 wks. RESULTS: All freshly-mixed specimens showed the highest fluoride ion release after 1 week, then the release rates dropped quickly to become largely stabilized after 3 wks. After one 4-min exposure to APF gel the initial fluoride ion release increased significantly for all materials. The highest rates were during the first day, but then dropped very quickly to again become largely stabilized after usually 3 wks. Exposure to NaF and CaF2 did not usually result in significantly sustained fluoride ion release by any material. The order of release/uptake for all three agents was Fuji II LC > Fuji IX GP > Ketac-Molar. The mechanism of fluoride ion release after the application of different fluoride recharging agents is not clear. It may occur partly by washout of recharge agents that are retained in the pores and cracks of the restorative materials, for APF gel is viscous and difficult to wash off completely with deionized water; by erosion of surfaces by low pH agents, or by the subsequent release of fluoride ions from within the cement matrix. PMID- 11763932 TI - Microleakage and adaptation of Class II packable resin-based composites using incremental or bulk filling techniques. AB - PURPOSE: To compare the ability of three packable resin-based composite (RBC) systems (ALERT, SureFil, and Solitaire), placed and light-cured in either incremental layers or in bulk, to seal the gingival margin of Class II preparations when the gingival margin is placed apical to the cementoenamel junction. MATERIALS AND METHODS: Packable RBCs were used to restore 60 extracted human premolars with Class II preparations using an incremental-cure technique (each layer no greater than 2 mm in thickness when light-cured) or a bulk-cure technique (n=10). Manufacturers' directions were followed; the cure technique was the only variable. After the restorations were completed, the specimens were thermocycled, stained, sectioned, and viewed under a light microscope for microleakage at the gingival margin. RESULTS: All specimens showed leakage at the gingival margin. No statistically significant difference was found between the bulk-cure and incremental-cure techniques for each of the RBC systems evaluated. ALERT had significantly less leakage than SureFil and Solitaire. PMID- 11763933 TI - Effect of temporary materials on bond strength of resin-modified glass-ionomer luting cements to teeth. AB - PURPOSE: To evaluate the effect of temporary materials on the bond strength of resin-modified glass-ionomer luting cements to teeth. MATERIALS AND METHODS: 240 freshly extracted bovine central incisors were ground to expose enamel and dentin surface. Fuji Lute and Vitremer Luting Cement were bonded to enamel and dentin surfaces after pretreatment for 1 week with (1) a eugenol-containing cement (Propac), (2) a eugenol-free cement (Freegenol Temporary Pack), (3) a polycarboxylate cement (HY-Bond Temporary Cement Hard), (4) a chemically cured temporary restorative resin (Plast Seal), and (5) a light-cured temporary restorative resin (Fermit). The flattened enamel and dentin surfaces were used as controls. After bonded specimens were stored in water at 37 degrees C for 24 hrs, the tensile bond strength was measured at a crosshead speed of 0.5 mm/min. The data were statistically analyzed by one-way ANOVA and Dunnett's Post-hoc Procedure (P < 0.05). RESULTS: Plast Seal had no adverse effect on the tensile bond strength of Fuji Lute on both enamel and dentin surfaces, while the other temporary materials revealed significant decrease in bond strength. In Vitremer Luting Cement, Propac, and Fermit, as well as Plast Seal demonstrated tensile bond strengths similar to the controls. PMID- 11763934 TI - Evaluation of floss types for interproximal plaque removal. AB - PURPOSE: To evaluate the efficacy of four different floss types for interproximal plaque removal on the normal dentition. MATERIALS AND METHODS: 24 dental hygiene students tested each of four different floss types: waxed, unwaxed, woven and shred-resistant. At baseline, all subjects received a prophylaxis to become plaque-free and identical flossing instructions were given. Subjects were then instructed not to brush, floss, or rinse for 3 days to allow for plaque development. On the fourth day, each subject's teeth were disclosed and scored using O'Leary's Plaque Index. Subjects were then randomly assigned one of the four floss types to use throughout the dentition, following which a second plaque record was assessed. Subjects were timed while flossing, and then completed a 10 cm Visual Analogue Scale (VAS) scoring their degree of discomfort/comfort and ease of use for each specific type of floss. This protocol was followed until all four floss types were tested by each subject. Results analyzed reductions in total interproximal plaque score (TIPS), anterior (teeth) interproximal plaque score (AIPS), and posterior (teeth) interproximal plaque score (PIPS). RESULTS: The greatest reduction in TIPS and PIPS was with waxed floss (68.87%, 66.54% respectively) and in AIPS with woven floss (75.15%). Post-hoc testing using Tukey's method revealed no significant differences among the four floss types. VAS scores revealed shred-resistant most comfortable (6.99) while unwaxed was least (4.29). These results indicated minimal differences in the efficacy of different types of floss, their degree of comfort and ease of use. PMID- 11763935 TI - Buccal absorption of triclosan following topical mouthrinse application. AB - PURPOSE: To determine clinically the buccal absorption and plaque retention of triclosan from a mouthrinse containing 0.03% triclosan. MATERIALS AND METHODS: 15 ml of the triclosan oral rinse (N=9) or placebo mouthrinse (N=12) was used twice daily for 21 days in humans. Blood, dental plaque and the expectorated oral rinse were collected prior to, during the treatment period at given intervals, and 8 days after the treatment. Dental plaque and blood samples were collected 1 hr and 4 hr after the morning rinse, respectively. The oral retention of triclosan was calculated by subtracting the amount of triclosan recovered in the expectorate from the triclosan dose applied (4.50 mg) in the mouthrinse. Plasma samples were analyzed for free triclosan (the parent molecule) and its glucuronide and sulfate conjugates, whereas dental plaque was analyzed only for total triclosan. RESULTS: No significant treatment-related adverse effects were observed during the clinical phase of the study. The average daily oral retention of triclosan was calculated to be 0.660 mg, which is 7.33% of the triclosan dose applied (2 x 4.50 mg). Plaque contained an average 20.5-46.4 microg of triclosan per g of plaque collected. At various sampling times, mean plasma concentrations were: no detectable triclosan, 63.8-86.3 microg/ml of triclosan glucuronide and 8.23-18.0 ng/ml of triclosan sulfate. The mean total triclosan plasma concentration ranged from 74.5 to 94.2 microg/ml with plateau concentrations reached after 2 days of dosing. Eight days after the last treatment the triclosan plasma concentration returned to baseline levels (< 2 ng/ml). PMID- 11763936 TI - Effectiveness of two fluoride dentifrices to arrest root carious lesions. AB - PURPOSE: To compare the effectiveness of Prevident 5000 Plus (5,000 ppm F) and Colgate Winterfresh Gel (1100 ppm F) to arrest root carious lesions. MATERIALS AND METHODS: 201 subjects with at least one root carious lesion were recruited from dental school patients. They were randomly assigned to use either Prevident 5000 Plus (5000 ppm F) or Colgate Winterfresh Gel (1100 ppm F) as sodium fluoride in the same silica base. Measurements of lesion hardness, area, distance from the gingival margin, cavitation and plaque were recorded at baseline and after 3 months by a single examiner. RESULTS: After 3 months 38% of subjects using Prevident 5000 Plus and 10% using Winterfresh Gel had one or more lesions that had become hard (P < 0.001). Non-cavitated lesions at baseline were more likely to become hard than cavitated lesions. Compared to the Winterfresh group there was significant increase in the distance from the base of the lesion to the gingival margin and plaque scores were reduced in those using Prevident 5000 Plus. PMID- 11763937 TI - Comparative anticaries efficacy of sodium fluoride and sodium monofluorophosphate dentifrices. A two-year caries clinical trial on children in New Jersey and Puerto Rico. AB - PURPOSE: To provide a head-to-head comparison of the anticaries efficacy associated with two commercially-available and American Dental Association accepted dentifrices: Crest Cavity Fighting Toothpaste with Fluoristat, containing 0.243% sodium fluoride in a silica base, and Colgate Great Regular Flavor Fluoride Toothpaste, containing 0.76% sodium monofluorophosphate in a dicalcium phosphate dihydrate base. The study was conducted in harmony with the published 1988 American Dental Association guidelines for studies geared toward this purpose. MATERIALS AND METHODS: The study employed a double-blind, parallel groups, multi-center two-treatment design, and involved third, fourth, and fifth grade schoolchildren from Newark, New Jersey, and from the Cidra and Lares areas of Puerto Rico. Qualifying subjects were stratified according to age and sex, and were randomly assigned to the two treatment groups, with multiple subjects in the same household all assigned to the dentifrice randomly allocated to the first among them. Caries examinations were conducted in accordance with U.S. Food and Drug Administration guidelines for the clinical evaluation of drugs to prevent dental caries. After treatment assignment, study participants were instructed to brush their teeth at home with their assigned dentifrice at least twice daily. Brushing instructions were reinforced by the presentation of educational films and lectures at school, by semi-annual mailings to parents, and through the periodic distribution of small novelty gifts along with the dentifrice deliveries, in order to enhance the interest and enthusiasm of study participants. Post-baseline examinations were performed after 1 and after 2 yrs of product use. Two thousand four hundred seventy-nine (2,479) subjects completed this 2-yr study. For these subjects, the mean (S.D.) DFS scores at baseline were 2.77 (3.35) for the Crest group, and 2.66 (3.18) for the Colgate group. For caries increment after 1 yr, the respective means were 1.68 (2.53) and 1.70 (2.57). After 2 yrs, the mean caries increments were 3.56 (4.11) for the Crest group, and 3.56 (4.05) for the Colgate group. RESULTS: The analysis of the 2-yr caries increment scores support the conclusion that the anticaries efficacy associated with Colgate Great Regular Flavor Fluoride Toothpaste is equivalent to that associated with Crest Cavity Fighting Toothpaste with Fluoristat, in accordance with the procedures and standards provided by the published guidelines of the American Dental Association. Further, consistent with those same standards, the results of this study serve to lend additional support to the conclusion that dentifrices formulated with sodium monofluorophosphate provide an equivalent level of anticaries efficacy as to those formulated with sodium fluoride. PMID- 11763938 TI - Traumatic neuroma of the anterior tongue. PMID- 11763939 TI - An advanced toothbrush with improved plaque removal efficacy. AB - PURPOSE: To compare the plaque removal efficacy and safety of a new advanced manual toothbrush, the Oral-B CrossAction, with seven other toothbrushes. MATERIALS AND METHODS: Seven independent, cross-over design clinical studies were conducted using the same examiner who was blind to the identity of the test products and treatment assignments. In each study, approximately 75 healthy adult subjects from a general population brushed with their randomly assigned toothbrush (CrossAction or comparison brush) at Visit 1 for 1 min without supervision or instruction in brushing technique. Subjects returned after a 1 week washout period and brushed with the alternate toothbrush (Visit 2). Plaque was evaluated before and after brushing using the Rustogi Modified Navy Plaque Index. Statistical analyses were conducted by an independent statistician who remained blind to the identity of all test products. RESULTS: Each of the toothbrushes tested provided significant (P < or = 0.0001) reductions in plaque scores after a single brushing. In each of the studies, the CrossAction toothbrush removed significantly (P < or = 0.0001) greater amounts of whole mouth, gingival margin, and approximal plaque than the compared toothbrush. All toothbrushes were found to be safe, with no changes in oral tissues or restorations observed over the course of each study. The results from these studies were consistent, demonstrating that the CrossAction toothbrush significantly enhances the ability of subjects to remove more plaque during normal brushing compared to seven other toothbrushes. PMID- 11763940 TI - A comparative clinical investigation of a novel toothbrush designed to enhance plaque removal efficacy. AB - PURPOSE: To investigate the safety and efficacy of a new toothbrush with a novel brush head design (Oral-B CrossAction) in comparison with seven leading manual brushes. MATERIALS AND METHODS: Seven independent clinical studies, each involving approximately 100 healthy subjects from a general population, were carried out using a crossover design. In each study, the Oral-B CrossAction toothbrush was compared with an alternative brush for plaque removal efficacy. Plaque was evaluated before and after brushing for 60 s using the Proximal/Marginal Plaque Index. Subjects were randomly assigned to the two brushes in each study and after brushing at visit 1 they returned after a further 2 weeks to repeat the procedure with the second brush. RESULTS: All toothbrushes in the seven studies significantly reduced levels of plaque from their pre brushing values and were found to be safe with no evidence of oral soft tissue trauma. In each of the studies, the CrossAction was found to be significantly (P < 0.05) more effective than the comparison brush for whole mouth plaque scores, as well as for plaque scores at the gingival margin and proximal surfaces. Advantages in favor of the CrossAction ranged from 9.8% to 23.2% for whole mouth plaque, from 5.3% to 20.6% for the gingival margin and from 12.8% to 24.5% for proximal surfaces. It was concluded that the novel brush head design of the CrossAction toothbrush provides enhanced plaque removal, especially from proximal surfaces, and that this toothbrush is significantly more effective than all seven toothbrushes tested. PMID- 11763942 TI - A new toothbrush design. PMID- 11763941 TI - A 3-month comparative investigation of the safety and efficacy of a new toothbrush: results from two independent clinical studies. AB - PURPOSE: To compare the efficacy of a new toothbrush featuring a novel brush head design with those of two established toothbrushes by measuring plaque and gingivitis over a period of 12 weeks. MATERIALS AND METHODS: The Oral-B CrossAction toothbrush was compared with the Dr. Best InterDent and Crest DeepSweep toothbrushes in two independent, parallel-group, examiner-blind clinical studies. Each study involved approximately 100 healthy individuals from a general population. At baseline, after 23-25 hrs of no oral hygiene, oral hard and soft tissues were examined and whole mouth, marginal and approximal plaque scores and whole mouth gingivitis scores were recorded. Subjects in the two studies were asked to use their assigned toothbrush twice a day. No instruction in brushing technique or brushing time was given. After a period of 6 weeks and finally after 12 weeks, subjects in the studies were reassessed for oral tissue status, and their plaque and gingival indices were rescored. RESULTS: In each of the two studies, the tested toothbrushes significantly reduced levels of plaque and gingivitis. The CrossAction toothbrush was, however, more effective in reducing both plaque and gingivitis over 12 weeks, the differences in favor of the CrossAction being statistically significant. All the toothbrushes tested in this investigation were found to be safe with no evidence of hard or soft tissue trauma. PMID- 11763943 TI - Development and laboratory evaluation of a new toothbrush with a novel brush head design. AB - Despite many developments in manual toothbrush design, plaque removal at the back of the mouth and at approximal surfaces remains inadequate, yet it is at these sites in particular that plaque accumulates and leads to the development of gingival disease. Improved oral hygiene can be achieved by better brushing technique and by increasing brushing time, but a change in behavior patterns is almost impossible to achieve for the majority of individuals. What is required is a brush head design that maximizes plaque removal, regardless of how the user brushes. As a result of a detailed investigation into the action of bistles during brushing, the Oral-B CrossAction toothbrush has been developed. It incorporates bristles angled at 16 degrees in a unique CrissCross design arranged along the horizontal axis of the toothbrush. Laboratory studies have demonstrated that this development significantly enhances interproximal penetration and cleaning effectiveness when compared with an identical brush head with vertical rather than angled bristles. Laboratory comparisons with more than 80 leading manual toothbrushes from around the world demonstrate a consistent, significant advantage for the new CrossAction toothbrush, both with respect to interproximal penetration and cleaning effectiveness. These results suggest that the CrossAction toothbrush has the potential to remove greater amounts of plaque, especially from the approximal surfaces, than conventional toothbrushes incorporating vertical bristles or more traditional tuft designs. PMID- 11763944 TI - Desensitizing efficacy of a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride. AB - PURPOSE: To evaluate the relative effectiveness provided by a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base (Colgate Sensitive Maximum Strength) for reducing dentin hypersensitivity over an 8-wk period, as compared to that provided by a commercially-available antihypersensitivity dentifrice containing 5.0% potassium nitrate and 0.76% sodium monofluorophosphate in a dicalcium phosphate base (Fresh Mint Sensodyne dentifrice). MATERIALS AND METHODS: To qualify for participation in this examiner blind study, male and female adults from the San Francisco, California area were required to present with tactile and air blast dentin hypersensitivity in at least 2 non-molar teeth at two examinations, spaced 1 wk apart. Qualifying subjects were randomized into two treatment groups, which were balanced for gender, age, and baseline sensitivity scores. Subjects were provided with a soft bristled toothbrush. Examinations for tactile and air blast sensitivity were repeated after 4 wks' use of the study dentifrices, and again after 8 wks' usage. RESULTS: 101 subjects complied with the protocol, and completed the entire study. After 4 wks, subjects assigned to the Colgate Sensitive Maximum Strength group exhibited a statistically significant improvement over the Fresh Mint Sensodyne dentifrice group with respect to tactile sensitivity scores, and a statistically significant improvement over the Sensodyne dentifrice group with respect to air blast sensitivity scores. Correspondingly significant improvements were presented after 8 wks. Thus, the results of this examiner-blind clinical study support the conclusion that Colgate Sensitive Maximum Strength dentifrice provided superior levels of control of tactile and air blast sensitivity than did the clinically tested, commercially-available Sensodyne anti-hypersensitivity dentifrice. PMID- 11763945 TI - Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices. AB - PURPOSE: To investigate the relative effectiveness provided by a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base (Colgate Sensitive Maximum Strength dentifrice) for reducing dentin hypersensitivity over an 8-wk period, as compared to that provided by a commercially-available antihypersensitivity dentifrice containing 5.0% potassium nitrate and 0.76% sodium monofluorophosphate in a dicalcium phosphate base (Fresh Mint Sensodyne dentifrice). MATERIALS AND METHODS: To qualify for participation in this examiner-blind clinical study, male and female adults from the central New Jersey area were required to present with tactile and air blast dentin hypersensitivity in at least two non-molar teeth at two examinations, spaced 1 wk apart. Qualifying subjects were randomized into two treatment groups, which were balanced for gender, age, and baseline sensitivity scores. Subjects were provided with a soft-bristled toothbrush. Examinations for tactile and air blast sensitivity were repeated after 4 wks' use of the study dentifrices, and again after 8 wks' usage. 97 subjects complied with the protocol, and completed the entire study. RESULTS: After 4 wks, subjects assigned to the Colgate Sensitive Maximum Strength dentifrice group exhibited a statistically significant improvement over the Sensodyne dentifrice group with respect to tactile sensitivity scores, and a statistically significant improvement over the Sensodyne dentifrice group with respect to air blast sensitivity scores. Correspondingly significant improvements were presented after 8 wks. Thus, the results of this examiner-blind clinical study support the conclusion that the Colgate Sensitive Maximum Strength dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base provided superior levels of control of tactile and air blast sensitivity than the clinically tested, commercially available anti-hypersensitivity dentifrice Sensodyne dentifrice containing 5.0% potassium nitrate and 0.76% sodium monofluorophosphate in a dicalcium phosphate base. PMID- 11763946 TI - Effect of plasma arc curing on the microleakage of Class V resin-based composite restorations. AB - PURPOSE: To evaluate the effect of plasma arc light-curing on the microleakage of Class V resin-based composite (RBC). MATERIALS AND METHODS: Facial and lingual Class V cavities were prepared at the cemento-enamel junction of extracted third molars. Restorations of the two materials (Z250; Amelogen) were placed, using the supplied dentin adhesives (Single Bond; PQ 1, respectively), and light-cured by either a halogen light curing unit (H) or a plasma arc curing unit (P). After thermal cycling, the teeth were immersed in methylene blue dye, then sections of the restored teeth were visually assessed for leakage. RESULTS: No leakage was observed at the interface between enamel and RBC in any restoration in this study. At gingival margins, the incidence of leakage (slight/severe) was: Z250 H = 2/4, P = 6/6; Amelogen H = 3/4, P = 1/12, where n = 16. The greatest incidence of leakage was observed in restorations cured by the plasma arc method. A two-way ANOVA of leakage data rankings showed curing method to be a significant factor (P = 0.002), restorative material not to be a significant factor (P = 0.24), and no significant interaction between material and curing method (P = 0.38). PMID- 11763948 TI - Physical properties of the dentin-enamel junction region. AB - PURPOSE: To determine the physical properties between enamel and dentin at the dentin-enamel junction (DEJ) region of natural tooth structure. MATERIALS AND METHODS: Ultimate tensile cohesive strengths of the DEJ region of human and bovine teeth were measured using a microtensile test, and the nanohardness and Young's modulus from deep enamel to superficial dentin of human teeth were measured using a nanoindentation tester. RESULTS: The mean ultimate tensile cohesive strengths of bovine and human DEJ region were 47.7 MPa and 51.5 MPa, respectively. The nanohardness, dynamic hardness and Young's modulus of the DEJ region showed moderate values between those of enamel and dentin. Comparison of the cohesive strength of the human DEJ region with previous results of the bond strength of resin bonding systems indicate that current resin bonding systems might reproduce the biological adhesion of enamel to dentin in terms of the tensile strength. Moreover, the indentation properties of the DEJ region showed higher values than those of the underlying dentin or of resin impregnated dentin. PMID- 11763947 TI - Effect of stepped vs. continuous light curing exposure on bond strengths to dentin. AB - PURPOSE: To compare the 10-min and 24-hr shear bond strengths of three dentin bonding systems, polymerized with either a standard (Optilux 401) light for 60 s, or a stepped curing light (Elipar Highlight) that delivered a low light intensity for 10 s followed by high intensity for 50 s. MATERIALS AND METHODS: Three bonding systems were used to bond two resin-based composites (RBC) to dentin at 34 degrees +/- 2C using the two curing lights. Single Bond (SB) and Prime & Bond 2.1 (P&B) were used with Z100 RBC, and EBS bonding system was used with Pertac II RBC. Ten specimens from each combination were debonded at 37 degrees +/- 1C 10 min after starting to light cure the bonding system. Ten other specimens were stored in water at 37 degrees +/- 1C for 24 hrs before debonding at 37 degrees +/ 1C (total 120 teeth). RESULTS: The 10-min mean shear bond strengths were: Standard Cure; EBS 11.9 +/- 2.9 MPa, SB 14.6 +/- 2.2 MPa, P&B 14.7 +/- 4.2 MPa: Stepped Curing; EBS 7.4 +/- 2.1 MPa, SB 13.0 +/- 3.6 MPa, P&B 15.6 +/- 4.8 MPa. The 24-hr mean shear bond strengths were: Standard Cure; EBS 14.8 +/- 5.1 MPa, SB 25.1 +/- 3.3 MPa, P&B 25.2 +/- 8.8 MPa: Stepped Curing; EBS 15.1 +/- 4.6 MPa, SB 21.9 +/- 5.9 MPa, P&B 17.3 +/- 9.2 MPa. Three way ANOVA showed significant main effects for light, bonding system and time and no 2- or 3-way interaction effects at P = 0.01. The Least-Squares Means test with Sidak's adjustment for Multiple Comparisons showed that the bond strengths obtained using the standard light were significantly greater than the bond strengths obtained using the stepped curing light (P < 0.01). The 24-hr bond strengths were significantly greater (P < 0.01) than the 10-min bond strengths. The bond strengths obtained with EBS were significantly less than SB and P&B (P < 0.01), but there were no significant differences between SB and PB (P = 0.9752). PMID- 11763949 TI - Composite surfaces after finishing and polishing techniques. AB - PURPOSE: To evaluate the effect of finishing and polishing techniques on surface roughness of resin-based composites (RBCs). MATERIALS AND METHODS: Forty specimens of each material were cured under Mylar strips and immersed in artificial saliva for 1 wk. Samples were tested with a profilometer to obtain baseline average surface roughness (Ra). Specimens of both RBCs were then finished and polished according to four techniques: (1) Sof-Lex disks; (2) Sof Lex disks followed by Prisma Gloss; (3) Enhance points; (4) Enhance points followed by Prisma Gloss application. New readings of the roughness pattern were carried out and the difference of post-polishing and baseline values were analyzed. RESULTS: ANOVA test (alpha = 0.05) did not show differences between materials (P = 0.9393) nor interaction effects (P = 0.3094), but significant difference among the finishing/polishing techniques were detected (P = 0.0157). Tukey's test showed that the smoothest surface was obtained when the specimens were treated by Sof-Lex followed by Prisma Gloss polishing paste; and the worst results were obtained after using Enhance points alone. PMID- 11763950 TI - Human pulpal response to direct pulp capping with an adhesive system. AB - PURPOSE: To evaluate clinically and microscopically the human pulp response when directly capped with an adhesive system or calcium hydroxide over short (9-12 days) and long (53-204 days) experimental periods. MATERIALS AND METHODS: Fifty one sound human premolars scheduled for orthodontic extraction, had their pulp horns gently exposed with a diamond point. Debris in the pulp wound was washed out with a sterile saline solution. The pulps were then capped with either an adhesive system (Scotchbond Multi-Purpose Plus) or calcium hydroxide. All teeth were subsequently restored with resin-based composite (Z-100) according to the manufacturer's instructions. After the experimental periods, the teeth were extracted and processed for light microscopic examination. RESULTS: Short-term: the pulp tissue capped with SBMP-P exhibited dilated and congested blood vessels associated with a moderate inflammatory response and blanching of pulp cell nuclei. Long-term: no evidence of healing and bridge formation was observed. A persistent mild inflammatory pulp response was present. Micro-abscesses were detected in three cases associated with bacterial infiltration. Calcium hydroxide stimulated early pulp repair and dentin bridging which extended into the longest period. PMID- 11763951 TI - Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices. AB - PURPOSE: To demonstrate through clinical pharmacokinetic studies that triclosan does not accumulate in blood or plasma in human subjects who regularly use triclosan-containing dentifrice. MATERIALS AND METHODS: Three clinical pharmacokinetic studies were conducted to assess the blood or plasma levels of triclosan following toothbrushing with dentifrice formulations containing triclosan. In Study 1, both a single-dose and a multiple-dose phase were conducted. In the single-dose phase, subjects brushed one time with 1.25 g dentifrice containing 0.3% triclosan (3.75 mg triclosan dose) and ingested all of the dentifrice. Blood samples were collected at multiple time points from pre dose to 72 hrs post-dose and analyzed for total triclosan levels. In the multiple dose phase, these same subjects brushed three times daily as in the single-dose phase. This pattern was followed for 12 consecutive days. Blood samples were taken for triclosan analysis at multiple time points up to 48 hrs after the first dose of day 12. Study 2 was a parallel, open-labeled clinical study to compare triclosan blood levels from twice daily brushing with 1 gm of dentifrice containing 0.2% triclosan to twice daily ingestion of 20 ml of a 0.01% triclosan aqueous solution over a period of 21 days. Blood samples were taken for triclosan analysis at baseline and at 4 hrs after the morning dose on days 7, 14, and 21. Study 3 was a parallel, double-blind, 12-wk brushing study with dentifrice containing 0.2% triclosan or a matching placebo. Blood samples were taken for triclosan analysis at baseline and at 3 and 12 wks at 4 hrs after the morning dose. RESULTS: In the single-dose study, Triclosan was absorbed into the systemic circulation with a T(1/2) of the terminal plasma concentration ranging between 6 63 hrs. The mean AUC(0-inf) after a single dose was found to be 2,809 ng x hr/ml. After 12 days of three times daily toothbrushing and ingestion of the dental slurry, the mean triclosan plasma concentration was 352 ng/ml in the steady state period, and the mean AUC in a 24-hr period (AUC24) was found to be 8,460 ng x hr/ml. This AUC24 was normalized for the number of brushings for comparison to the AUC(0-inf) after a single brushing. There was no significant (P = 0.93) difference between these AUC values suggesting a complete elimination of daily triclosan dose and no increase in the triclosan level during repeated brushing/ingestion. In the two other dentifrice studies, the triclosan blood concentration appeared to reach a steady state level by day 7 and was maintained at the steady state level (14 to 21 ng/ml) for up to 12 wks. These results support the conclusion that the elimination of a daily triclosan dose is complete and no accumulation of triclosan was observed even after three times daily toothbrushing with 1.25 g dentifrice containing 0.3% triclosan and full ingestion of the dentifrice. PMID- 11763952 TI - A model for clinical evaluation of anti-microbial effects of agents on plaque colonization. AB - PURPOSE: To evaluate a new improved method of microbial analysis in a cross-over clinical study by investigating the efficacy of a single application of an essential oil-containing (EOC) dentifrice as compared to its vehicle control (VC) over a 6-hr period. MATERIALS AND METHODS: Acrylic stents with retention areas for 7, 3 mm x 3 mm hydroxyapatite (HA) squares were fabricated for 12 subjects. 30 min following stent placement, one HA square was removed and sampled for viable microflora. After stent replacement, subjects were assigned either the EOC dentifrice or its VC and brushed under supervision for 1 min. Stents remained in place for the next 6 hrs. A HA square was removed at hourly intervals for 6 hrs following brushing. The microflora was analyzed for total anaerobes on Schaedler's media, for total gram-negative anaerobes on Schaedler-NV selective media, and for total Fusobacterium species on CVE selective media. Plates were incubated anaerobically at 37 degrees C for 2-5 days. Colony forming units were calculated. For each time point, pairwise t-tests were performed using the adjusted means and the pooled error term from the analysis of variance (ANOVA). RESULTS: Treatment with the EOC dentifrice resulted in a statistically reduced plaque growth. Differences were seen as reductions in: (1) total gram-negative anaerobes seen from 1-6 hrs (P < or = 0.011), (2) total anaerobic bacteria which achieved significance at 3 hrs and continued through 6 hrs (P < or = 0.005), and (3) Fusobacterium species as seen from 4-6 hrs (P < or = 0.002). PMID- 11763954 TI - Oral melanoacanthoma of the attached gingiva. PMID- 11763953 TI - Effect of mouthwash and accelerated aging on the color stability of esthetic restorative materials. AB - PURPOSE: To evaluate the color stability of esthetic restorative materials after immersion in mouthwashes and accelerated aging. MATERIALS AND METHODS: Compomers and resin-based composites (RBC) were measured at baseline and repeatedly after immersion in three kinds of mouthwash (Listerine, Peridex, Rembrandt Age Defying) for 24 hrs and 7 days, and after aging for 150 kJ/m2. Color was measured according to CIE L*a*b* color scale on a reflection spectrophotometer. RESULTS: After immersion for 7 days, the mouthwash groups did not produce significantly higher color changes than the distilled water group, except with some mouthwashes used with Tetric-Ceram. After immersion for 7 days and aging for 150 kJ/m2, the mouthwash groups did not produce significantly higher color changes than the distilled water group. Aging in weathering chamber produced color change (deltaE*) of 1.1-3.9, which was mainly influenced by the material. With some exceptions, the color changes from immersion of the RBCs and compomers in mouthwashes were not perceptible (deltaE*<3.3). PMID- 11763955 TI - Managing the office safety program. PMID- 11763956 TI - Auditory behaviour of a parasitoid fly (Emblemasoma auditrix, Sarcophagidae, Diptera). AB - Females of the parasitoid fly Emblemasoma auditrix find their host cicada (Okanagana rimosa) by its acoustic signals. In laboratory experiments, fly phonotaxis had a mean threshold of about 66 dB SPL when tested with the cicada calling song. Flies exhibited a frequency dependent phonotaxis when testing to song models with different carrier frequencies (pulses of 6 ms duration and a repetition rate of 80 pulses s(-1)). However, the phonotactic threshold was rather broadly tuned in the range from 5 kHz to 11 kHz. Phonotaxis was also dependent on the temporal parameters of the song models: repetition rates of 60 pulses s(-1) and 80 pulses s and pulse durations of 5-7 ms resulted in the highest percentages of phonotaxis performing animals coupled with the lowest threshold values. Thus, parasitoid phonotaxis is adapted especially to the temporal parameters of the calling song of the host. Choice experiments revealed a preference of a song model with 9 kHz carrier frequency (peak energy of the host song) compared with 5 kHz carrier frequency (electrophysiologically determined best hearing frequency). However, this preference changed with the relative sound pressure level of both signals. When presented simultaneously, E. auditrix preferred 5-kHz signals, if they were 5 dB SPL louder than the 9-kHz signal. PMID- 11763957 TI - Effects of binaural decorrelation on neural and behavioral processing of interaural level differences in the barn owl (Tyto alba). AB - The effect of binaural decorrelation on the processing of interaural level difference cues in the barn owl (Tyto alba) was examined behaviorally and electrophysiologically. The electrophysiology experiment measured the effect of variations in binaural correlation on the first stage of interaural level difference encoding in the central nervous system. The responses of single neurons in the posterior part of the ventral nucleus of the lateral lemniscus were recorded to stimulation with binaurally correlated and binaurally uncorrelated noise. No significant differences in interaural level difference sensitivity were found between conditions. Neurons in the posterior part of the ventral nucleus of the lateral lemniscus encode the interaural level difference of binaurally correlated and binaurally uncorrelated noise with equal accuracy and precision. This nucleus therefore supplies higher auditory centers with an undegraded interaural level difference signal for sound stimuli that lack a coherent interaural time difference. The behavioral experiment measured auditory saccades in response to interaural level differences presented in binaurally correlated and binaurally uncorrelated noise. The precision and accuracy of sound localization based on interaural level difference was reduced but not eliminated for binaurally uncorrelated signals. The observation that barn owls continue to vary auditory saccades with the interaural level difference of binaurally uncorrelated stimuli suggests that neurons that drive head saccades can be activated by incomplete auditory spatial information. PMID- 11763958 TI - Cutaneous electrical oscillation in a weakly electric fish, Gymnarchus niloticus. AB - An African electric fish, Gymnarchus niloticus. ceases its electric organ discharge for a prolonged time in response to external electrical signals. During the cessation of electric organ discharges from the electric organ, a weak sinusoidal signal (approximately 0.1 mV cm(-1)) near the fish's previous discharge frequency was recorded near the body. The oscillatory potentials at all points on the body surface were synchronized and had a complex spatial distribution. The source of the potential was determined to be within the dermal tissue. Electroreceptive central neurons that responded to a moving target near the fish with normal electric organ discharges also responded to the same target when the electric organ discharge was interrupted and the potential from the skin existed. This result suggests that the fish may be able to electrolocate objects without the discharge from the electric organ. PMID- 11763959 TI - Temporally patterned sound pulse trains affect intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus. AB - This study examined the effect of temporally patterned pulse trains on intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus. Intensity sensitivity of inferior collicular neurons was expressed by the dynamic range and slope of rate-intensity functions. Inferior collicular neurons with non-monotonic rate-intensity functions have smaller dynamic ranges and larger slopes than neurons with monotonic or saturated rate intensity functions. Intensity sensitivity of all inferior collicular neurons improved by increasing the number of non-monotonic rate-intensity functions when the pulse repetition rate of pulse trains increased from 10 to 30 pulses per second. Intensity sensitivity of 43% inferior collicular neurons further improved when the pulse repetition rate of pulse trains increased still from 30 to 90 pulses per second. Frequency sensitivity of inferior collicular neurons was expressed by the Q10, Q20, and Q30 values of threshold frequency tuning curves and bandwidths of isointensity frequency tuning curves. Threshold frequency tuning curves of all inferior collicular neurons were V-shape and mirror-images of their counterpart isointensity frequency tuning curves. The Q10, Q20, and Q30 values of threshold frequency tuning curves of all inferior collicular neurons progressively increased and bandwidths of isointensity frequency tuning curves decreased with increasing pulse repetition rate in temporally patterned pulse trains. Biological relevance of these findings to bat echolocation is discussed. PMID- 11763960 TI - Task-specific association of photoreceptor systems and steering parameters in Drosophila. AB - Visual motion processing enables moving fruit flies to stabilize their course and altitude and to approach selected objects. Earlier attempts to identify task specific pathways between two photoreceptor systems (peripheral retinula cells 1 6, and central retinula cells 7 + 8) and three steering parameters (wingstroke asymmetry, abdomen deflection, hindleg deflection) attributed course control and object fixation to peripheral retinula cells 1-6-mediated simultaneous reactions of these parameters. The present investigation includes first results from fixed flying or freely walking ninaE17 mutants which cannot synthesize the peripheral retinula cells 1-6 photoreceptor-specific opsin. Retention of about 12% of the normal course control and about 58% of the object fixation in these flies suggests partial input sharing for both responses and, possibly, a specialization for large-field (peripheral retinula cells 1-6) and small-field (central retinula cells 7 + 8) motion. Such signals must be combined to perceive relative motion between an object and its background. The combining links found in larger species might explain a previously neglected interdependence of course control and object fixation in Drosophila. -Output decomposition revealed an unexpected orchestration of steering. Wingstroke asymmetry and abdomen deflection do not contribute in fixed proportions to the yaw torque of the flight system. Different steering modes seem to be selected according to their actual efficiency under closed-loop conditions and to the degree of intended turning. An easy experimental access to abdominal steering is introduced. PMID- 11763961 TI - Presynaptic effects of biogenic amines modulating synaptic transmission between identified sensory neurons and giant interneurons in the first instar cockroach. AB - Intracellular recording was used to investigate the modulatory effects of serotonin and octopamine on the identified synapses between filiform hair sensory afferents and giant interneurons in the first instar cockroach, Periplaneta americana. Serotonin at 10(-4) mol l(-1) to 10(-3) mol l(-1) reduced the amplitude of the lateral axon-to-ipsilateral giant interneuron 3 excitatory postsynaptic potentials. and octopamine at 10(-4) mol l(-1) increased their amplitude. Similar effects were seen on excitatory postsynaptic potentials in dorsal giant interneuron 6. Several lines of evidence suggest that both substances modulate the amplitude of excitatory postsynaptic potentials by acting presynaptically, rather than on the postsynaptic neuron. The fitting of simple binomial distributions to the postsynaptic potential amplitude histograms suggested that, for both serotonin and octopamine, the number of synaptic release sites was being modulated. Secondly, the amplitudes of miniature excitatory postsynaptic potentials recorded in the presence of tetrodotoxin were unaffected by either modulator. Finally, recordings from contralateral giant interneuron 3, which has two identifiable populations of synaptic inputs, showed that each modulator had a more pronounced effect on excitatory postsynaptic potentials evoked by the lateral axon than on those evoked by the medial axon. Immunocytochemistry confirmed that neuropilar processes containing serotonin are present in close proximity to these synapses. PMID- 11763962 TI - Hearing dimorphism, trait variation and conflicts over space in the thorax of the bushcricket Requena verticalis (Listroscelidinae: Tettigoniidae: Orthoptera). AB - The hearing system of Requena verticalis is sexually dimorphic. Previous work has shown size of the auditory spiracle determines absolute threshold and as female spiracles are, on average, larger than males, females are more sensitive to the main energy of the male call. In all measured traits in morphology and physiology, females showed lower coefficient of variation than males. This difference was significant for bulla volume and hearing threshold. In addition, female ear size covaries with thorax dimensions but this is not so in males. Such a finding suggests stabilising selection on ear size in females, perhaps explained by the requirement of females to recognise and locate the male. As the auditory bulla is larger in females than males, so occupying thoracic space, we suggest a possible trade-off in this brachypterous species between hearing sensitivity and sound production. Finally, we examine relative growth of body structures not associated with hearing and those that influence hearing sensitivity. Scaling, where traits are under strong selection, may result in allometry. Female hearing traits show positive allometry with absolute size and while the relationship between bulla volume and spiracle area was positively allometric in females this was not the case for males. PMID- 11763963 TI - The effect of shape parameters on maximal detection distance of model targets by honeybee workers. AB - The influence of several spatial parameters on the maximal detection distance of a target by approaching foraging honeybees was examined. The roles of target diameter, color and luminance contrasts have been already demonstrated in earlier studies. The present study used, for the first time, dissected flower like targets that differed in addition to diameter (D) and area (pi(D/2)(2) = Acir) also in the length of contour line (C), the area of the colored "petals" (Acol) and the degree of dissectedness as expressed mainly by the ratio Acol2/C. The color and luminance contrasts were identical for all targets. Our results confirm the importance of size. However, we demonstrate for the first time, that full circular shapes have the greatest maximal detection distance among targets of equal diameters, and even more than dissected targets with equal Acol and double D. The parameter Acol2/C was found as the best predictor of maximal detection distance of vertically presented targets with varying diameter and degree of dissection for honeybee workers. We propose that an increase in the colored area and decrease in contour line is advantageous due to the fact that it increases the amount of contrast that the target as a whole produces against its background. PMID- 11763964 TI - Nectar feeding by the hovering hawk moth Macroglossum stellatarum: intake rate as a function of viscosity and concentration of sucrose solutions. AB - Although nectar feeding in insects has long been studied, the knowledge of the effect of nectar energy content on the ingestion dynamics separately from the viscosity of the fluid is very limited. To determine the effects of both factors on the feeding behavior of the hovering hawk moth Macroglossum stellatarum, we developed a method to independently manipulate sucrose concentrations and viscosity. The intake rate was analyzed as a function of sucrose concentration, the concentration at constant viscosity (kept constant by adding tylose, an inert polysaccharide), and of the different viscosities of a 30% weight/weight (w/w) sucrose solution (by adding different amounts of tylose). By increasing the concentration, and thus its viscosity, the solution intake rate (in microl s ( 1)) decreased beyond a 20% w/w sucrose solution. For a 30% sucrose solution, the intake rate decreased with increasing viscosity. At constant viscosity, the solution intake rate decreased beyond a 30% w/w sucrose solution. However, if we considered the quantity of sucrose ingested per unit time (sucrose intake rate), the same fitted maximum was attained for both series in which the sucrose concentration changed (33.6% w/w). Results suggest that the gustatory input affects the dynamics of fluid ingestion separately from the viscosity. PMID- 11763965 TI - Worker piping in honey bee swarms and its role in preparing for liftoff. AB - Worker piping, previously reported only in hives, was observed in swarms as they prepared to liftoff to fly to a new home. Pipers are excited bees which scramble through the swarm cluster, pausing every second or so to emit a pipe. Each pipe consists of a sound pulse which lasts 0.82 +/- 0.43 s and rises in fundamental frequency from 100-200 Hz to 200-250 Hz. Many. if not all, of the pipers are nest site scouts. The scouts pipe when it is time to stimulate the non-scouts to warm themselves to a flight-ready temperature (35 degrees C) in preparation for liftoff. The time-course of worker piping matches that of swarm warming, both start at a low level, about an hour before liftoff, and both build to a climax at liftoff. When we excluded pipers from bees hanging in the cool, outermost layer of a swarm cluster, we found that these bees did not warm up. The form of worker piping that we have studied in swarms differs from the form of worker piping that others have studied in hives. We call the two forms "wings-together piping" (in swarms) and "wings-apart piping" (in hives). PMID- 11763966 TI - Structure and function of pore-forming beta-barrels from bacteria. AB - Crystallographic studies of the past ten years have revealed that many outer membrane proteins and bacterial toxins are constructed on the beta-barrel motif. Two structural classes can be identified. The first class, represented by the porins, includes monomeric or multimeric proteins where each beta-barrel is formed from a single polypeptide. The second class features proteins where the beta-barrel is itself a multimeric assembly, to which each subunit contributes a few beta-strands. In addition to structural investigations, much work has also been devoted to the functional aspects of these proteins, and to the relationships between structure and function. Here we present a review of the structural and the functional properties of some of the best-studied examples of these various classes of proteins, namely the general-diffusion, specific and ligand-gated porins, multidrug efflux proteins and the staphylococcal toxin alpha hemolysin. PMID- 11763967 TI - A XerD recombinase with unusual active site motifs in Streptococcus pneumoniae. AB - XerD belongs to the site specific recombinases of the integrase family of proteins that catalyze recombination events via a phosphotyrosine intermediate. Sequence alignments and crystal structure resolution of E. coli XerD and related enzymes demonstrated the importance of four conserved amino acids R-H-R-H that are spaced along the C-terminal domain in addition to a conserved K and the active site Y, all of which have been implicated in catalysis. The deduced amino acid sequence of the putative S. pneumoniae XerD contained three unique replacements at the conserved positions resulting in L-Q-R-L; moreover, the active site Y was the penultimate amino acid residue, and the extreme C-terminal region suggested to be involved in interaction of E. coli XerD with XerC was lacking. Severe growth defects in a loss-of-function xerD mutant are consistent with an important in vivo function of the S. pneumoniae XerD protein. Highly related xerD genes with similar unusual amino acid replacements were found in S. mitis, S. mutans and S. pyogenes but not in other Gram-positive bacteria, although the genetic environment was very similar in many species. There are at least another four genes in the S. pneumoniae KNR_7/87 genome encoding Xer related peptides, one of which was identified as the xerC homologue. The xerD and xerC genes were present in a sample of 20 S. pneumoniae strains whereas the other xer genes appear to be absent in some of the strains and are more closely related to integrases of phage and transposon origin. PMID- 11763968 TI - Ushers and secretins: channels for the secretion of folded proteins across the bacterial outer membrane. AB - Gram-negative bacteria have evolved a number of pathways for extracellular protein secretion. Proteins targeted for secretion in Gram-negative bacteria must cross the outer membrane in addition to the cytoplasmic membrane. This must be accomplished without compromising the barrier properties of the outer membrane and is further complicated by the fact that proteins may fold prior to secretion outside the cell. This review will discuss the usher and secretin families of integral outer membrane proteins, which function to allow the secretion of folded proteins in Gram-negative bacteria. PMID- 11763969 TI - Bacteriophage holins: deadly diversity. PMID- 11763970 TI - Transport capabilities encoded within the Bacillus subtilis genome. AB - We here describe all recognized established and putative transport proteins encoded within the genome of Bacillus subtilis. These fall into four classes of established transporter types: (1) channel proteins, (2) secondary active transporters, (3) primary active transporters, and (4) group translocators of the sugar-transporting phosphotransferase system (PTS). Additionally, some transporters are recognized that utilize an unknown mode of action or energy coupling mechanism. The secondary carriers (which represent the majority of Bacillus transporters) are subdivided according to substrate specificity and family association. Characteristics of the families as well as the individual transport systems are presented when sufficient information is available. The recognized transporters fall into 58 families including 4 channel types, 42 secondary carrier types, 3 primary carrier types, 4 PTS-types and 5 unknown types. PMID- 11763971 TI - A web-based Tree View (TV) program for the visualization of phylogenetic trees. AB - We designed a web-based program, Tree View (TV), which uses a dynamic data structure algorithm to draw the phylogenetic tree for a family of homologous proteins. This program has a user-friendly interface and can be easily implemented into other programs for convenient protein sequence analysis. It is available at our web site: http://www.biology.ucsd.edu-yzhai/biotools.html. PMID- 11763972 TI - SPOUT: a class of methyltransferases that includes spoU and trmD RNA methylase superfamilies, and novel superfamilies of predicted prokaryotic RNA methylases. PMID- 11763973 TI - An inventory of genes encoding RNA polymerase sigma factors in 31 completely sequenced eubacterial genomes. AB - Sigma factors are important elements involved in transcriptional regulation of gene expression by conferring promoter specificity to RNA polymerase. The number of sigma factor encoding genes in 31 completely sequenced bacterial genomes were compared. Two unrelated families of sigma factors, the sigma70- and the sigma54 family were identified previously. The sigma70-family can be further subdivided into two distantly related groups: the sigma70 subfamily and the poorly characterized ECF subfamily. A total of 215 sigma factors could be attributed to these subfamilies. The construction of phylogenetic trees allows subclassifications of sigma factor encoding genes within the subfamilies. With the exception of Deinococcus radiodurans, all species possess a housekeeping primary sigma factor. Free-living species possess a higher number of both sigma70 type and ECF alternative sigma factors than pathogens or symbionts associated with animals. Different bacterial species exhibit large differences in the number of alternative sigma factor encoding genes and consequently huge flexibility in their transcriptional regulatory patterns. Transcriptional regulation in terms of regulons controlled by alternative sigma factors is a late evolving phenomenon. The current nomenclature for sigma factor encoding genes is confusing and should be revised. PMID- 11763974 TI - Sequence analysis and structure prediction of 23S rRNA:m1G methyltransferases reveals a conserved core augmented with a putative Zn-binding domain in the N terminus and family-specific elaborations in the C-terminus. AB - N1-methylation of G748 within 23S ribosomal RNA results in resistance to the macrolide tylosin in Streptomyces. In contrast, the Escherichia coli mutant lacking N1-methylation of G745 exhibits increased resistance to viomycin, in addition to severe defects of growth characteristics. Both methylated guanines are located in hairpin 35, in domain II of prokaryotic 23S rRNA. G748 and G745 are modified by related S-adenosylmethionine-dependent methyltransferases (MTases), TlrB and RrmA respectively. Earlier sequence comparisons allowed identification of the AdoMet-binding site, however the catalytic site and the target-recognition region of these enzymes could not be delineated unambiguously. In this work, we carried out sequence-to-structure threading of the rRNA:m1G MTase family against the database of known structures to Identify those "missing regions". Our analysis confirms the earlier prediction of the AdoMet-binding site, but suggests a different location of the putative catalytic center than was previously postulated. We predict that RrmA and TlrB possess two regions that may be responsible for specific interactions with their target nucleic acid sequences: a putative Zn-finger domain in the N-terminus and the variable domain close to the C-terminus, which indicates that 23S rRNA MTases exhibit the primary structural organization distinct from other nucleic acid MTases, despite sharing the common catalytic domain. PMID- 11763975 TI - Contraceptive practices of women after abortion in Turkey. AB - OBJECTIVES: The aim ofthis study was to determine the postabortion contraception choices of women and the subsequent reduction in pregnancy rate. The changes in method of contraception during the 1-year follow-up period were also assessed. METHODS: Ninety women decided to practice family planning methods following an abortion procedure. The family planning choices of the postabortion family planning group were determined by active immediate family planning counselling. The control group, which consisted of 23 women who had had an abortion and wanted to become pregnant again, were followed-up for 1 year to determine their pregnancy rate. The pregnancy rates and methods used were determined during a 12 month follow-up period. RESULTS: Following counselling, 79.64% of the patients signed for immediate family planning practice. In the postabortion family planning group, one out of 90 patients (1.1%, Pearl index 1.29) practising contraception with a condom became pregnant. However, ten out of 23 (43.5%, Pearl index 54.2) patients in the control group became pregnant during the 1-year follow-up period (p < 0.05). In the postabortion family planning group, intrauterine devices (IUDs) (n = 43), injectable monthly contraceptives (n = 24) and tubal ligation (n = 9) were the most commonly preferred methods, with 47%, 27% and 10% of the women using these methods, respectively. At the end of the 12 month period, the drop-out rate among women using the injectable monthly contraceptives was significantly higher (13 patients, 54%) compared to other methods (p < 0.05). In one case out of 43 using an IUD (2.38%), the IUD was expelled during follow-up. CONCLUSION: The use of postabortion family planning significantly decreased the postabortion pregnancy rate. The use of an IUD was the preferred immediate method of choice. Use of injectable monthly contraceptives was the method with the highest drop-out rate. The expulsion rate of postabortion IUDs was acceptable in our practice. The pregnancy rate in the control group was lower than the physiological fecundity would predict. This may suggest that, although couples plan to get pregnant, they do not concentrate on the ideal conditions for conception or they do, in fact, practice some form of family planning. PMID- 11763976 TI - Oral versus vaginal misoprostol for cervical priming in first-trimester abortion: a randomized trial. AB - The objective of this study was to compare the oral and vaginal administration of misoprostol for cervical priming before surgical abortion up to 63 days' gestation. A total of 900 pregnant women, with ages ranging from 18 to 42 years, who asked for pregnancy termination, were included in this study. Women were randomly allocated to one of the following groups: oral administration of 400 microg misoprostol, 8 h before aspiration; and vaginal self-administration of 400 microg misoprostol, 4 h before aspiration. During admission, all subjects were checked on a 15-min basis. The preoperative cervical dilatation achieved was the main outcome assessed. The cervix was dilated (Hegar > or = 8) in 348 (78%) subjects from the oral treatment group and in 391 (87%) women from the vaginal treatment group; this difference was statistically significant (p = 0.0004). The mean dilatation achieved in the oral treatment group was 8.1 mm (SD 1.6 mm) and it was 8.5 mm (SD 1.5 mm) in the vaginal treatment group; this difference was statistically significant (p = 0.0001). The frequencies of side-effects such as nausea, vomiting, diarrhea and chills reported by women from the vaginal misoprostol group were 10, 8, 18 and 4 times lower, respectively, than those reported by subjects from the oral misoprostol group. In conclusion, vaginal self administration of misoprostol was the best administration route, as it obtained the same or greater priming effectiveness of the cervix in half the time with a much lower frequency of side-effects. PMID- 11763977 TI - Randomized outpatient clinical trial of medical evacuation and surgical curettage in incomplete miscarriage. AB - OBJECTIVE: To compare the efficacy and safety of misoprostol in outpatient medical evacuation with surgical curettage in uncomplicated incomplete spontaneous miscarriage. METHODS: Eighty women with a history of vaginal bleeding, and passage of some products of the conceptus were randomized into two groups. Forty patients in Group 1 received 200 microg misoprostol q.i.d. after the application of 200 microg intravaginal misoprostol for 5 days; 40 patients in Group 2 had a surgical curettage performed. All of the patients were re-evaluated after 10 days. The success rates, mean number of days of bleeding, mean decreases in hemoglobin levels, the complications and the rates of patient dissatisfaction in the two groups were compared. RESULTS: The success rate in the misoprostol administered group was 95% [corrected]. Although the mean number of days of bleeding was significantly higher in the misoprostol-administered group, the mean decreases in hemoglobin values in the two groups were not significantly different. The patient dissatisfaction rate was 2.5% in the misoprostol group, compared to 35% in the control group. The difference between the two groups was significant. CONCLUSIONS: The use of misoprostol in the outpatient treatment of uncomplicated incomplete spontaneous miscarriage is safe and effective and can be an alternative to surgical evacuation and expectant management. PMID- 11763978 TI - Determinants of abortion among women undergoing artificial termination of pregnancy. AB - OBJECTIVES: In order to determine factors involved in the contraceptive practice of women undergoing artificial abortion, a prospective questionnaire survey was carried out. METHODS: Women (n = 800) requesting artificial abortion were compared with women (n = 1000) admitted to or visiting the department for reasons other than abortion. The SPSS program was used for statistical analysis between 1998 and 1999. Multiple logistic regression analysis was applied to evaluate the factors influencing the contraceptive practice of the aborters. RESULTS: Reliable contraceptive methods were used significantly less frequently by the aborters than by the control group (19.1% vs. 55%, p < 0.001, adjusted odds ratio (AOR), 0.46; 95% confidence interval (CI), 0.3-0.7). The contraceptive choice of the aborters depended significantly on their low income (AOR, 1.87; 95% CI, 1.5-2.4). The likelihood of abortion was significantly lower among those informed by a health-care provider (AOR, 0.56; 95% CI, 0.4-0.8) or the media (AOR, 0.51; 95% CI, 0.4-0.7). Awareness of reliable methods was also an important factor (AOR, 0.25; 95% CI, 0.1-0.5). CONCLUSIONS: It appears that a further decrease of the abortion ratio could be attained through an intensive media campaign and improved education. PMID- 11763979 TI - Factors influencing women's satisfaction with birth control methods. AB - OBJECTIVES: To study the extent to which variation in satisfaction with a birth control method is explained by variation in perceived physical and psychological effects. METHODS: A population survey among 1466 German women was carried out. Within the overall sample, 1303 women had ever used oral contraceptives, 996 had relied on condoms, 342 had ever used intrauterine devices (IUD), 428 had used natural family planning and 139 women were sterilized. For each method a woman had ever used, she answered questions about satisfaction with the method, concerns about getting pregnant or suffering health risks during use, ease of use, changes in sexual relationship, relationship with the partner and mood. Past and current users of oral contraceptives and IUDs and sterilized women additionally reported changes in menstrual bleeding. RESULTS: Variation in satisfaction was, for a large part, explained by variation in health concerns among oral contraceptive users, by variation in perceived changes in the quality of the sexual relationship among condom users, by perceived ease of use among IUD users and sterilized women, and by variation in pregnancy concern among natural family planning users. CONCLUSION: Counselling about these perceived experiences is most likely to result in greater satisfaction and therefore improved compliance. PMID- 11763980 TI - Blood pressure stability in a normotensive population during intake of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 g gestodene. AB - OBJECTIVES: Evaluation of the impact of a monophasic gestodene-based oral contraceptive on blood pressure in a population that was normotensive at baseline. METHODS: Data on blood pressure were retrospectively analyzed from four large prospective clinical phase III trials with an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene. A total of 1342 young fertile women were evaluated after 12 treatment cycles. RESULTS: The mean systolic and diastolic blood pressure did not change during treatment. Approximately 89% of women were normotensive at baseline and 93% at the end of the treatment period. Only a few women (< or = 1%) were hypertensive at baseline; an increase in this prevalence was not found after 12 cycles of oral contraceptive use. The number of women who experienced a blood pressure increase was almost identical to the number who experienced a decrease. Approximately 90% of women had either a negligible blood pressure change of maximal +/- 10 mmHg or a decrease. CONCLUSIONS: The findings of this retrospective analysis confirm that monophasic gestodene has a negligible effect on blood pressure in users who were normotensive before treatment began. PMID- 11763981 TI - Transfer of drospirenone to breast milk after a single oral administration of 3 mg drospirenone + 30 microg ethinylestradiol to healthy lactating women. AB - Drospirenone (DRSP) is a synthetic progestogen which has been developed in combination with ethinylestradiol (EE) for use as an oral contraceptive (Yasmin, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of DRSP were evaluated in serum and breast milk from lactating women who received a single oral dose of 3 mg DRSP + 30 microg EE, to determine the fraction of the dose of DRSP which transfers to breast milk. Nine healthy, lactating women were included into the present study and pharmacokinetic data were obtained from six participants. The maximum DRSP concentrations (data given as mean +/- standard deviation) were reached on average 2.5+/-1.2 and 2.8+/-1.3 h in serum and breast milk, respectively after oral administration of 3 mg DRSP + 30 microg EE, and amounted on average to 30.8+/-14.4 and 13.5+/-11.7 ng DRSP/ml in serum and breast milk. The mean breast milk versus serum concentration ratios of DRSP increased from 0.16 to 0.57 within 2 h after dosing and decreased to 0.16 after 24 h. The average ratio of AUC0-48 h, values in breast milk versus serum was 0.23+/-0.09. The mean DRSP concentration in breast milk over the 24-h period after dosing was 3.7+/-1.9 ng/ml. The amount of DRSP measured to be transferred into breast milk in the six women participating in the present study was, on average, 635 ng (range 256.2-1357.9 ng) within 24 h, corresponding to about 0.02% of the maternal dose. Based on the average concentration of the drug in breast milk over 24 h and assuming a daily ingestion of approximately 800 ml breast milk, the daily dose that reaches an infant via breast milk is estimated to be approximately 3 microg DRSP. The subjective and objective tolerances of 3 mg DRSP + 30 microg EE were good, with no adverse events reported. PMID- 11763982 TI - A multinational evaluation of the efficacy, safety and acceptability of the Protectaid contraceptive sponge. AB - OBJECTIVE: The Protectaid sponge (Gefar Pharma, Switzerland) is a new feminine barrier contraceptive method containing three low-dose spermicidal agents. In order to evaluate its efficacy and safety profiles, an international, multicenter study has been conducted in four countries. METHODS: Healthy, presumably fertile and sexually active women were enrolled in this study and were followed at 15 days, 3, 6, 9 and 12 months. Contraceptive efficacy was assessed by a pregnancy test, while safety was evaluated by performing gynecological examinations as well as reporting adverse events. The 'acceptability' of the sponge by the women was assessed through a standard questionnaire. RESULTS: A total of 129 women were enrolled in the study, generating 1182 cycles of use of the sponge. The overall efficacy rate was 77%, with no significant influence of age or parity. Acceptability was high, with 85% of subjects being symptom- or problem-free while using the sponge. Finally, the safety profile was very good, with no clinically significant evidence of local or systemic adverse reactions. CONCLUSION: The new Protectaid sponge is a safe and effective non-hormonal contraceptive method for women. PMID- 11763983 TI - Neural basis and biological function of masking by light in mammals: suppression of melatonin and locomotor activity. AB - Light influences mammalian circadian rhythms in two different ways: (1) It entrains endogenous oscillators (clocks), which regulate physiology and behavior; and (2) it affects directly and often immediately physiology and behavior (these effects are also referred to as masking). Masking effects of light on pineal melatonin, locomotor activity, and the sleep-wake cycle in mammals and man are reviewed. They seem to represent a universal response in this group. The review reveals that the mechanism of photic inhibition of melatonin is fairly well understood, whereas only little is known about the influence of light on other circadian rhythm outputs, such as locomotor activity. PMID- 11763984 TI - Spontaneous and light-evoked discharge of the isolated abdominal nerve cord of crayfish in vitro reveals circadian oscillations. AB - We examined the well-known spontaneous discharge (SD) and light-evoked (PD) discharge of the crayfish caudal photoreceptor for the possible existence of a daily rhythm in spike frequency. To do this, we isolated the abdominal nerve cord in vitro and studied its discharge frequency in constant darkness. Single cosinor analysis revealed significant SD and PD circadian rhythms (P < .05) with periods tau = 24.4h and 24.2h, respectively. These oscillations correspond to an endogenous circadian discharge of the caudal photoreceptor that is enhanced by light. The importance of this rhythm in the adaptive behavior of crayfish is discussed. PMID- 11763985 TI - Adjustability of the circadian clock in the cockroaches: a comparative study of two closely related species, Blattella germanica and Blattella bisignata. AB - A single 2h light pulse (250 lux) was given at various times to phase shift the locomotor circadian rhythm of two species of closely related cockroaches, Blattella bisignata and Blatella germanica. The phase-response curve (PRC) of both species showed a similar pattern. Phase delays and advances were induced by light pulse during the early and late subjective night, respectively, while no clear phase shifting was elicited during the subjective day. However, the magnitude of the phase delay (1.89h +/- 0.66h) and advance (0.69h +/- 0.36h) of B. bisignata was significantly larger than that of B. germanica (0.78h +/- 0.38h and 0.35h +/- 0.18h, respectively). This result indicates the superior adjustability of the circadian clock in B. bisignata. The period-response curve (PdRC) was also constructed for both species. Although both species did not show great flexibility in circadian period changes, the phase shifts were significantly correlated with the period changes in the advance zone of B. bisignata (r = 0.72, P < .1). This allowed the circadian clock of B. bisignata to display better entrainability since the phase advance adjustment was significantly more difficult than that of phase delay. The results indicate the overall adjustability of the circadian clock of B. germanica is inferior to that of B. bisignata. The significance of this finding is discussed from an ecological perspective. PMID- 11763986 TI - S20098 affects the free-running rhythms of body temperature and activity and decreases light-induced phase delays of circadian rhythms of the rat. AB - Mammalian endogenous circadian rhythms are entrained to the environmental day night cycle by light exposure. Melatonin is involved in this entrainment by signaling the day-night information to the endogenous circadian pacemaker. Furthermore, melatonin is known to affect the circadian rhythm of body temperature directly. A striking property of the endogenous melatonin signal is its synthesis pattern, characterized by long-term elevated melatonin levels throughout the night. In the present study, the influence of prolonged treatment with the melatonin agonist S20098 during the activity phase of free-running rats was examined. This was achieved by giving S20098 in the food. The free-running body temperature and activity rhythms were studied. The present study shows that enhancement of the melatonin signal, using S20098, affected the free-running rhythm by gradual phase advances of the start of the activity phase, consequently causing an increase in length of the activity phase. A well-known feature of circadian rhythms is its time-dependent sensitivity for light. Light pulse exposure of an animal housed under continuous dark conditions can cause a phase shift of the circadian pacemaker. Therefore, in a second experiment, the influence of melatonin receptor stimulation on the sensitivity of the pacemaker to light was examined by giving the melatonin agonist S20098 in the food during 1 day prior to exposure to a 60-min light pulse of 0, 1.5, 15, or 150 lux given at circadian time (CT) 14. S20098 pretreatment caused a diminished light pulse induced phase shift when a light pulse of low light intensity (1.5 lux) was given. S20098 treatment via the food was sufficient to exert chronobiotic activity, and S20098 treatment resulting in prolonged overstimulation of melatonin receptors is able to attenuate the effect of light on the circadian timing system. PMID- 11763987 TI - Effect of light wavelength on suppression and phase delay of the melatonin rhythm. AB - Different wavelengths of light were compared for melatonin suppression and phase shifting of the salivary melatonin rhythm. The wavelengths compared were 660 nm (red), 595 nm (amber), 525 nm (green), 497 nm (blue/green), and 470 nm (blue). They were administered with light-emitting diodes equated for irradiance of 130 muW/cm2. Fifteen volunteers participated in all five wavelength conditions and a no light control condition, with each condition conducted over two consecutive evenings. Half-hourly saliva sam ples were collected from 19:00 to 02:00 on night 1 and until 01:00 on night 2. Light was administered for the experimental conditions on the first night only from midnight to 02:00. Percentage melatonin suppression on night 1 and dim light melatonin onset (DLMO) for each night were calculated. The shorter wavelengths of 470, 497, and 525 nm showed the greatest melatonin suppression, 65% to 81%. The shorter wavelengths also showed the greatest DLMO delay on night 2, ranging from 27 to 36 min. The results were consistent with the involvement of a scotopic mechanism in the regulation of circadian phase. PMID- 11763988 TI - Genetic analysis of morningness and eveningness. AB - We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability--the sum of additive and nonadditive genetic influences--for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. PMID- 11763989 TI - Parental enforcement of bedtime during childhood modulates preference of Japanese junior high school students for eveningness chronotype. AB - We examined the effect of home bedtime discipline during childhood on morningness and eveningness (M-E) preference by Japanese junior high school students. M-E was assessed by the M-E Questionnaire (MEQ) of Torsvall and Akerstedt (the higher the score, the greater the preference for morningness), and parental determination of bedtime during childhood was ascertained using an original questionnaire. The average M-E score of adolescents living in urban Kochi City (mean +/- SD; 15.10 +/- 3.42) was significantly lower (P < .01) than the score of those in suburban districts (16.14 +/- 3.44). Overall, 43.1% of the junior high school students in Kochi City compared to 53.0% of the students living in suburban districts had their bedtime decided during childhood by parents (P < .01). In Kochi City, the M E score for boys (14.62 +/- 3.51) was lower (P < .01) than girls (15.53 +/- 3.28). During childhood, parents decided the bedtime for 49% of the girls compared to 36.6% of the boys (P < .01). Boys whose bedtime was not decided by parents during childhood had a somewhat stronger preference for eveningness (14.20 +/- 3.53) (P < .05) compared to those whose bedtime was decided by parents (15.12 +/- 3.36). The results suggest bedtime discipline at home during childhood has an effect on adolescent chronotype, modulating the extent of shift to evening ness in Japanese junior high school boys in particular. PMID- 11763990 TI - A pedigree of one family with delayed sleep phase syndrome. AB - The prevalence of delayed sleep phase syndrome (DSPS) has been estimated to be quite low. Although no genetic inheritance pattern has been described, it has been reported that close to 50% of DSPS patients have biological relatives with similar symptoms. A pedigree of one extended family with symptoms suggestive of DSPS has been identified. Morningness-eveningness questionnaires were administered to all first- and second-degree relatives of a proband identified with DSPS. A total of 51 (86%) questionnaires were returned, and 6 adult biological relatives of 27 (22%) showed a preference for eveningness, which is much higher than reported in the general population. Both the paternal and maternal branches contained affected individuals, suggesting the possibility of a bilineal mode of inheritance. While the trait did not obey simple Mendelian inheritance, the vertical patterns of transmission were consistent with either an autosomal dominant mode of inheritance with incomplete penetrance or a multifactorial mode of inheritance. These data provide some preliminary support to the notion that eveningness, and thus DSPS, may have a genetic component. The prevalence of symptoms suggestive of DSPS is higher in this family than reported in the general population. Case reports such as this support the utility of larger, more systematic studies. It is unclear whether this degree of familiarity is representative of that in the general population. PMID- 11763991 TI - Morning-evening administration time differences in digoxin kinetics in healthy young subjects. AB - Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration Cmax; Tmax, the time to reach Cmax; area under plasma concentration curve AUC; and elimination half-time T1/2 of digoxin were determined. Tmax was statistically significantly shorter (54 min) following 08:00 dosing com pared to 20:00 dosing (96 min). Although the Cmax was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except Tmax exhibited administration time dependency. PMID- 11763992 TI - Cisplatin-induced vomiting depends on circadian timing. AB - We examined whether the clock time of cisplatin plus antiemetic and diuretic administration affects the amount of cisplatin-associated emesis and severity of renal toxicity. We treated 22 patients with urogenital cancer with two courses of chemotherapy containing 70 mg/m2 of cisplatin. Cisplatin together with furosemide was administered in the morning (05:00) or evening (17:00) during two courses 1 month apart in a crossover fashion. Ondansetron was given either before or after cisplatin to control nausea and vomiting. The number of vomiting episodes, serum creatinine, serum urea nitrogen (BUN), creatinine clearance, and urinary beta-N acetyl glucosamidase (NAG) concentration were evaluated before and after each treatment course. Regardless of the timing of ondansetron, morning compared to evening cisplatin was always associated with greater vomiting in the first treatment course. However, prophylactic administration of ondansetron markedly diminished the impact of the clock time of cisplatin administration. Serum creatinine transiently decreased rather than increased 14 days after cisplatin and furosemide administration, while NAG excretion increased 3 days after cisplatin and furosemide administration. In the first course, serum creatinine levels were similar regardless of the clock time of cisplatin and furosemide administration. However, in the second course, serum creatinine rose in patients given evening cisplatin and furosemide, while it remained unchanged in those given morning cisplatin and furosemide. Moreover, the first course morning cisplatin and furosemide treatment was associated with less change in NAG excretion (less kidney toxicity) than the first course of evening cisplatin and furosemide treatment. The second course evening cisplatin and furosemide treatment was associated with an increase in NAG excretion compared to the first course of treatment, while morning cisplatin and furosemide treatment in the second course showed less change in NAG excretion compared to the first course. The clock time of cisplatin administration had an impact on the frequency of emesis. Prophylactic ondansetron, however, diminished the time-of-day dependency of cisplatin-induced vomiting. Administration of cisplatin and furosemide in the morning rather than evening appears to cause less renal damage, and this damage may be further reduced with aggressive hydration and routine administration of furosemide. PMID- 11763993 TI - Seasonal variation in the effect of a fixed dose of heparin on activated clotting time in patients prepared for open-heart surgery. AB - We investigated the effect of an injected bolus of 5 mg kg(-1) heparin at one circadian stage (08:30 to 11:00) on blood coagulation during different months of the year. Activated clotting times (ACTs) were assessed before and 5 min after heparin dosing to ensure extracorporeal circulation during open-heart surgery. The ACT data of 1083 presumably day-active Turkish patients (816 men and 267 women, mostly older than 46 years) who underwent coronary bypass surgery between 08:30 and 11:00 in the years from 1994 to 1997 were analyzed for annual rhythmicity. The ACT values obtained just before and 5 min after heparinization were subjected to cosinor analysis using a 365.25-day period to assess seasonality in basal ACT level and heparin effect. A small-amplitude annual rhythm with a wintertime peak was documented in the morning ACT in the group of 1083 patients. Rhythms of similar magnitude and staging were also detected in heparin effect on ACT in the 1083 patients and in subgroups categorized by gender. Circannual rhythmicity in the heparin effect on ACT was also documented in the elderly (> or = 45 years old), but not young (18-45 years old) patients. The annual mean effect of heparin on the ACT was statistically significantly greater in younger than older patients. The relatively low-amplitude circannual rhythm in heparin effect on ACT (approximately 10% of the annual mean) is not viewed as being meaningful in patient preparation for bypass surgery for the 5 mg kg(-1) level of heparin dose. PMID- 11763994 TI - A longitudinal investigation of seasonal variation in mood. AB - A prospective panel study was conducted to measure seasonality of mood in a random community sample in Melbourne, Australia (N = 245). Based on research into the structure of human mood, it was predicted that a lowering of mood in winter relative to summer would be observed in positive affect (PA) and behavioral engagement (BE), but not negative affect (NA). These variables were measured across summer and winter for 3 years. Consistent with the majority of research in the Northern Hemisphere, analyses on the entire sample found evidence of a small prospective season effect on the BE scale (explaining 2.1% of variance in BE scores). Also, as expected, no season effect was seen on the NA scale. In the entire sample, the season effect was not significant for PA, but joint factor analysis of the BE, PA, and NA scales confirmed that the season effect seen in the BE scale was largely due to items that were pure measures of PA. Winter pattern seasonality was both reliable across measures and significantly more marked among the subgroup of respondents who self-identified winter pattern of mood on the Seasonal Pattern Assessment Questionnaire. PMID- 11763996 TI - Exploring relationships in gene expressions: a partial least squares approach. AB - Microarray technology has revolutionized the way gene functions are monitored. Analysis of microarray data is a fast growing research area that interfaces various disciplines such as biology, biochemistry, computer science, and statistics. While various clustering and classification techniques have been successfully employed to group genes based on the similarity of their expression patterns, much is yet to be learned about the interrelationship of the expression levels among various genes. We approach this problem with a statistical technique called partial least squares that is capable of modeling a large number of variables each with relatively few observations. This property of the partial least squares methodology appears to be attractive for application to microarray data sets where the simultaneous expression levels of many genes are collected each at a few time points (or individuals). We use it to analyze publicly available microarray data on sporulation of budding yeast (Saccharomyces cerevisiae). We investigate a number of representative genes, one from each temporal group (based on the time of first induction) of positively expressed genes and show that in each case most of the variability was explained by only two partial regression terms based on all remaining genes. Moreover, the predicted expression levels of the representative genes from partial least squares fit very well on the average with the true expression levels over time. Finally, we compare the biological functions of the genes with largest coefficients with those of the predicted genes. In many cases, the genes are involved in similar or related biological functions including negative relationships. We show that this method can identify established gene relationships; we argue that it can be an exploratory tool for identifying potential gene relationships requiring further biological investigation. PMID- 11763995 TI - Adenovirus-mediated increase of HNF-3 levels stimulates expression of transthyretin and sonic hedgehog, which is associated with F9 cell differentiation toward the visceral endoderm lineage. AB - Retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells toward the visceral endoderm lineage is accompanied by increased expression of the Forkhead Box (Fox) transcription factors hepatocyte nuclear factor 3a (HNF 3alpha) and HNF-3beta, suggesting that they play a crucial role in visceral endoderm development. Retinoic acid stimulation results in a cascade of HNF-3 induction in which HNF-3alpha is a primary target for retinoic acid action and its increase is required for subsequent induction of HNF-3beta expression. Increased expression of HNF-3beta precedes activation of its known target genes, including transthyretin (TTR), Sonic hedgehog (Shh), HNF-1alpha, HNF-1beta, and HNF-4alpha. In order to examine whether increased HNF-3 expression is sufficient to induce expression of its downstream target genes without retinoic acid stimulation, we have used adenovirus-based expression vectors to increase HNF-3 protein levels in F9 cells. We demonstrate that adenovirus-mediated increase of HNF-3alpha levels in F9 cells is sufficient to induce activation of endogenous HNF-3beta levels followed by increased TTR and Shh expression. Furthermore, we show that elevated HNF-3beta levels stimulate expression of endogenous TTR and Shh without retinoic acid stimulation. Moreover, ectopic HNF-3 levels in undifferentiated F9 cells are insufficient to induce HNF-3alpha, HNF-1alpha, HNF 1beta, and HNF-4alpha expression, suggesting that their transcriptional activation required other regulatory proteins induced by the retinoic acid differentiation program. Finally, our studies demonstrate the utility of cell infections with adenovirus expressing distinct transcription factors to identify endogenous target genes, which are assembled with the appropriate nucleosome structure. PMID- 11763997 TI - Reversal of inhibition by the T7 concatemer junction sequence on expression from a downstream T7 promoter. AB - We have previously reported that placement of the phage T7 concatemer junction (CJ) just upstream of another gene on a plasmid in a T7 system proved to be inhibitory to expression of the downstream gene. We had hypothesized that the inhibition was a result of a readthrough transcript of the CJ element interacting with the translation start region of the downstream gene; also that in the absence of a T7 termination signal, transcription continued around the plasmid multiple times ("rolling circle" transcription), always juxtaposing the inhibitory CJ sequence proximal to the downstream gene mRNA. Two strong predictions were made from this model: 1) that introduction of a spacer sequence between the CJ element and the downstream gene should alleviate the inhibition, and 2) that reintroduction of a T7 transcription terminator should prevent rolling circle transcription, thereby reversing the inhibition by allowing some transcripts to be generated originating from the downstream promoter that did not contain the inhibitory CJ element upstream. We report here that both of these predictions have been fulfilled. However, the reversal of inhibition was only partial in the construct where the T7 terminator was reintroduced, indicating that there remains a residual inhibitory effect of the CJ element on expression of the downstream gene. A possible explanation is that the CJ element, acting as a pause site for transcription, blocks access to the downstream T7 promoter, thereby reducing transcription from that promoter. If this explanation is correct, steric hindrance of transcription starts resulting from an upstream RNA polymerase pause site may represent a previously unrecognized mechanism of transcriptional control. PMID- 11763998 TI - Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development. AB - The transcriptional mechanisms underlying tooth development are only beginning to be understood. Pitx2, a bicoid-like homeodomain transcription factor, is the first transcriptional marker observed during tooth development. Because Pitx2, Msx2, and Dlx2 are expressed in the dental epithelium, we examined the transcriptional activity of PITX2 in concert with Msx2 and the Dlx2 promoter. PITX2 activated while Msx2 unexpectedly repressed transcription of a TK-Bicoid luciferase reporter in a tooth epithelial cell line (LS-8) and CHO cell line. Surprisingly, Msx2 binds to the bicoid element (5'-TAATCC-3') with a high specificity and competes with PITX2 for binding to this element. PITX2 binds to bicoid and bicoid-like elements in the Dlx2 promoter and activates this promoter 45-fold in CHO cells. However, it is only modestly activated in the LS-8 tooth epithelial cell line that endogenously expresses Msx2 and Pitx2. RT-PCR and Western blot assays reveal that two Pitx2 isoforms are expressed in the LS-8 cells. We further demonstrate that PITX2 dimerization can occur through the C terminus of PITX2. Msx2 represses the Dlx2 promoter in CHO cells and coexpression of both PITX2 and Msx2 resulted in transcriptional antagonism of the Dlx2 promoter. Electrophoretic mobility shift assays demonstrate that factors in the LS-8 cell line specifically interact with PITX2. Thus, Dlx2 gene transcription is regulated by antagonistic effects between PITX2, Msx2, and factors expressed in the tooth epithelia. PMID- 11763999 TI - SpSoxB1 serves an essential architectural function in the promoter SpAN, a tolloid/BMP1-related gene. AB - Transcription of SpAN, which encodes a secreted protease related to tolloid and BMP 1, is differentially regulated along the animal-vegetal axis of the sea urchin embryo by a maternally initiated mechanism. Regulatory sites that bind SpSoxB1 and CBF (CCAAT binding factor) are essential for strong transcriptional activity because mutations of these elements reduce promoter activity in vivo 20- and 10-fold, respectively. Here we show that multimerized SpSoxB1 elements cannot activate transcription from the SpAN basal promoter in vivo. However, like other factors containing HMG-class DNA binding domains, SpSoxB1 does induce strong bending of DNA. The CBF binding site lies abnormally far from the transcriptional start site at -200 bp. We show that the SpSoxB1 site is not required if the CCAAT element is moved 100 bp closer to the transcriptional start site, replacing the SpSoxB1 site. This supports a model in which the bending of SpAN promoter DNA by SpSoxB1 facilitates interactions between factors binding to upstream and downstream regulatory elements. PMID- 11764001 TI - Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction. AB - To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg( 1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg( 1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated. PMID- 11764000 TI - Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis. AB - Peroxisome proliferators, which function as peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists, are a group of structurally diverse nongenotoxic hepatocarcinogens including the fibrate class of hypolipidemic drugs that induce peroxisome proliferation in liver parenchymal cells. Sustained activation of PPARalpha by these agents leads to the development of liver tumors in rats and mice. To understand the molecular mechanisms responsible for the pleiotropic effects of these agents, we have utilized the cDNA microarray to generate a molecular portrait of gene expression in the liver of mice treated for 2 weeks with Wy-14,643, a potent peroxisome proliferator. PPARalpha activation resulted in the stimulation of expression (fourfold or greater) of 36 genes and decreased the expression (fourfold or more decrease) of 671 genes. Enhanced expression of several genes involved in lipid and glucose metabolism and many other genes associated with peroxisome biogenesis, cell surface function, transcription, cell cycle, and apoptosis has been observed. These include: CYP2B9, CYP2B10, monoglyceride lipase, pyruvate dehydrogenase-kinase-4, cell death-inducing DNA-fragmentation factor-alpha, peroxisomal biogenesis factor 11beta, as well as several cell recognition surface proteins including annexin A2, CD24, CD39, lymphocyte antigen 6, and retinoic acid early transcript-gamma, among others. Northern blotting of total RNA extracted from the livers of PPARalpha-/- mice and from mice lacking both PPARalpha and peroxisomal fatty acyl CoA oxidase (AOX), that were fed control and Wy-14,643-containing diets for 2 weeks, as well as time course of induction following a single dose of Wy-14,643, revealed that upregulation of genes identified by microarray procedure is dependent upon peroxisome proliferation vis-a-vis PPARalpha. However, cell death inducing DNA-fragmentation factor-alpha mRNA, which is increased in the livers of wild-type mice treated with peroxisome proliferators, was not enhanced in AOX-/- mice with spontaneous peroxisome proliferation. These observations indicate that the activation of PPARalpha leads to increased and decreased expression of many genes not associated with peroxisomes, and that delayed onset of enhanced expression of some genes may be the result of metabolic events occurring secondary to PPARalpha activation and alterations in lipid metabolism. PMID- 11764002 TI - Complement plays an important role in gastric mucosal damage induced by ischemia reperfusion in rats. AB - Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress. PMID- 11764003 TI - Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs. AB - The effect of oxytocin (1 mg/kg s.c) on gastric acid secretion and on different experimentally induced gastric and duodenal ulcers was studied. The acute gastric ulcer models used were pylorus ligation, indomethacin, ethanol and histamine induced acute gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by cysteamine hydrochloride. Oxytocin showed significant antisecretory and antiulcer activity in pylorus ligated rats. Similarly oxytocin reduced the ulcer index in histamine induced gastric ulcers in guinea pigs and cysteamine induced duodenal ulcers in rats. The antiulcer and antisecretory effect was comparable to that of ranitidine (50mg/kg, i.p) though less in intensity. However, it did not show any gastric cytoprotective effect in ethanol and indomethacin induced ulcer models but ranitidine showed protection (p<0.05) in later model. Oxytocin enhanced gastric ulcer healing in acetic acid induced chronic gastric ulcer model. The reversal of oxytocin effect by atosiban, an oxytocin receptor antagonist indicates a role for oxytocin receptors. The antiulcer activity of oxytocin can be attributed to its antisecretory effect. PMID- 11764004 TI - Rearrangement of diflunisal acyl glucuronide into its beta-glucuronidase resistant isomers facilitates transport through the small intestine to the colon of the rat. AB - Many non-steroidal anti-inflammatory drugs (NSAIDs) which form acyl glucuronide conjugates as major metabolites have shown an antiproliferative effect on colorectal tumors. This study assesses the extent to which rearrangement of an acyl glucuronide metabolite of a model NSAID into beta-glucuronidase-resistant isomers facilitates its passage through the small intestine to reach the colon. Rats were dosed orally with diflunisal (DF), its acyl glucuronide (DAG) and a mixture of rearrangement isomers (iso-DAG) at 10 mg DF equivalents/kg. The parent drug DF appeared in plasma after all doses, with maximum concentrations of 20.5+/ 2.5, 28.8+/-8.3 and 11.0+/-1.6 microg DF/ml respectively, obtained at 3.8+/-0.3, 3.6+/-1.8 and 7.5+/-0.9 hr after the DF, DAG and iso-DAG doses respectively. At 48 hr, 16.2+/-3.3, 19.8+/-0.8 and 42.9+/-10.1% of the doses respectively were recovered in feces, with < or = 1% remaining in the intestine. About half of each dose was recovered as DF and metabolites in 48 hr urine: for DF and DAG doses, the majority was in the first 24 hr urine, whereas for iso-DAG doses, recoveries in the first and second 24 hr periods were similar. The results show that hydrolysis of both DAG and iso-DAG, and absorption of liberated DF, occur during passage through the gut, but that these processes occur more slowly and to a lesser degree for iso-DAG. The intrinsic hydrolytic capacities of various intestinal segments (including contents) towards DAG and iso-DAG were obtained by incubating homogenates under saturating concentrations of DAG/iso-DAG at 37 degrees C. Upper small intestine, lower small intestine, caecum and colon released 2400, 3200, 9200 and 22800 microg DF/hr/g tissue plus contents respectively from DAG substrate, and 18, 10, 140 and 120 microg DF/hr/g tissue plus contents respectively from iso-DAG substrate. The much greater resistance of iso-DAG to hydrolysis appears attributable to its resistance to beta glucuronidases. The data suggest that in rats dosed with DF, DAG excreted in bile would be substantially hydrolysed in the small intestine and liberated DF reabsorbed, but that portion which rearranges to iso-DAG would likely reach the colon. PMID- 11764005 TI - Inhibition of proliferation of HT-29 colon adenocarcinoma cells by carboxylate NSAIDs and their acyl glucuronides. AB - Many nonsteroidal anti-inflammatory drugs (NSAIDs) which have antiproliferative activity in colon cancer cells are carboxylate compounds forming acyl glucuronide metabolites. Acyl glucuronides are potentially reactive, able to hydrolyse, rearrange into isomers, and covalently modify proteins under physiological conditions. This study investigated whether the acyl glucuronides (and isomers) of the carboxylate NSAIDs diflunisal, zomepirac and diclofenac had antiproliferative activity on human adenocarcinoma HT-29 cells in culture. Included as controls were the carboxylate NSAIDs themselves, the non-carboxylate NSAID piroxicam, and the carboxylate non-NSAID valproate, as well as its acyl glucuronide and isomers. The compounds were incubated at 1-3000 microM with HT-29 cells for 24 hr, with [3H]-thymidine added for an additional 2 hr incubation. IC50 values were calculated from the concentration-inhibition response curves for thymidine uptake. The four NSAIDs inhibited thymidine uptake, with IC50 values about 200-500 microM. All of the NSAID acyl glucuronides (and isomers, tested in the case of diflunisal) showed antiproliferative activity broadly comparable to the parent drugs. This activity may stem from direct uptake of intact glucuronide/isomers followed by covalent modification of proteins critical in the cell replication process. However, hydrolysis during incubation and cellular uptake of liberated parent NSAID will play a role. In HT-29 cells incubated with zomepirac, covalently modified proteins in cytosol were detected by immunoblotting with a zomepirac antibody, suggesting that HT-29 cells do have the capacity to glucuronidate zomepirac. The anti-epileptic drug valproate had no effect on inhibition of thymidine uptake, though, surprisingly, its acyl glucuronide and isomers were active. The reasons for this are unclear at present. PMID- 11764006 TI - Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. AB - Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells under conditions that increase intracellular iron concentrations. We report here that after incubation with holotransferrin, which increases the concentration of ferrous iron in cancer cells, dihydroartemisinin, an analog of artemisinin, effectively killed a type of radiation-resistant human breast cancer cell in vitro. The same treatment had considerably less effect on normal human breast cells. Since it is relatively easy to increase the iron content inside cancer cells in vivo, administration of artemisinin-like drugs and intracellular iron-enhancing compounds may be a simple, effective, and economical treatment for cancer. PMID- 11764007 TI - Protein phosphatase inhibitor cantharidin inhibits steroidogenesis and steroidogenic acute regulatory protein expression in cultured rat preovulatory follicles. AB - The effect of cantharidin, a natural toxicant of blister beetles and a strong inhibitor of protein phosphatases types 1 and 2A, on luteinizing hormone (LH) induced synthesis of steroidogenic acute regulatory (StAR) protein was studied in a serum-free culture of preovulatory follicles. StAR protein is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of steroidogenesis, probably by promoting the transfer of cholesterol to the inner mitochondrial membrane and the cytochrome P450 side-chain cleavage (P450scc) enzyme. Treatment of preovulatory follicles dissected from ovaries of immature rats primed with pregnant mares' serum gonadotropin (10 IU) with LH for 24 h resulted in a dose-dependent increase in the level of StAR protein that reached a maximum at 100 ng LH/ml. This increase was associated with an increase in progesterone production. Treatment of follicles with increasing concentrations (10 - 1000 ng/ml) of cantharidin suppresssed LH (100 ng/ml)-induced StAR protein levels and progesterone production in a dose-dependent manner. The amount of P450scc protein and the conversion of 22R-hydroxycholesterol to progesterone were not affected by cantharidin. This indicates that cantharidin did not interfere with the activity of P450scc. Cantharidin also decreased StAR protein levels and progesterone production induced by the adenylate cyclase activator forskolin (10(-5) M) or a cAMP analog 8-Br-cAMP (0.5 mM). These results demonstrate that cantharidin inhibits the LH-induced StAR protein levels, and, thus, suggest that phosphoprotein phosphatase activity is required for the cAMP-protein kinase A stimulated steroidogenic activity of the preovulatory follicle. PMID- 11764008 TI - Semi-quantitative RT-PCR analysis of environmental influence on P450scc and PNMT mRNA expression in rat adrenal glands. AB - Environmental influence on brain function, particularly spatial learning and memory, has been extensively investigated, but little is known about the influence of environmental conditions on the functions of peripheral organs. In the present study, the effects of different housing conditions on the steady state levels of mRNAs encoding cholesterol side-chain cleavage enzyme (cytochrome P450scc) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands was examined to investigate the environmental influence on both adrenocortical and adrenomedullary functions. Behavioral changes of the animals housed in different conditions were first examined to assess the relevance of environmental manipulation used. In consistent with previous findings, housing of the animals in enriched conditions resulted in the significant reduction of spontaneous motor activity (locomotor activity and rearing) in comparison with housing in isolated conditions, thus indicating the relevance of housing conditions used in this work for investigating the environmental influence on adrenal function. Then, the effects of these housing conditions on P450scc and PNMT mRNA levels in adrenal glands were examined using semi-quantitative RT-PCR method. In comparison with the isolated group, the enriched group showed significantly higher levels of P450scc mRNA. In contrast, PNMT mRNA levels in the enriched group were significantly lower than those in the isolated group. These results propose the possibility that the environmental conditions may cause differential alterations in adrenocortical and adrenomedullary functions, although their possible association with behavioral changes still remains to be elucidated. PMID- 11764009 TI - Effects of resveratrol on human immune cell function. AB - Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol found in grapes and grape products such as red wine, has been reported to exhibit a wide range of biological and pharmacological activities both in vitro and in vivo. Because many of the biological activities of resveratrol, like the inhibition of cyclooxygenase, induction of CD95 signaling-dependent apoptosis, effects on cell division cycle and modulation of NF-kB activation, suggest a possible effect on the immune system, we evaluated the in vitro effects of resveratrol in three immune response models: i) development of cytokine-producing CD4+ and CD8+ T cells induced by stimulation of peripheral blood mononuclear cells (PBMC) with anti-CD3/anti-CD28; ii) specific antigen-induced generation of cytotoxic T lymphocytes; iii) natural killer (NK) activity of PBMC. The results showed that in vitro exposure to resveratrol produces a biphasic effect on the anti-CD3/anti CD28-induced development of both IFN-gamma- IL2- and IL4-producing CD8+ and CD4+ T cells, with stimulation at low resveratrol concentrations and suppression at high concentrations. Similarly, the compound was found to induce a significant enhancement at low concentrations and suppression at high concentrations of both CTL and NK cell cytotoxic activity. On the whole, the results of the study indicate that resveratrol modulates several human immune cell functions and suggest that this activity may be related to its effects on cytokine production by both CD4+ and CD8+ T cells. PMID- 11764010 TI - Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats. AB - Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission. PMID- 11764011 TI - Influence of antidepressant pharmacotherapy on behavioral treatment adherence and smoking cessation outcome in a combined treatment involving fluoxetine. AB - The authors examined whether serum fluoxetine levels influence behavioral treatment adherence and smoking cessation outcome. Nondepressed smokers (N = 989) from 16 centers were randomized on a double-blind basis to receive either fluoxetine (30 or 60 mg) or placebo plus 9 sessions of behavioral smoking cessation treatment. Fluoxetine and norfluoxetine blood levels were assayed 1 week after the quit date. Logistic regression was used to predict treatment completion and cessation outcome, controlling for gender, age, treatment site, and degree of nicotine dependence. Higher steady-state fluoxetine blood levels (fluoxetine + norfluoxetine) predicted less likelihood of dropping out, chi2(1, N = 820) = 3.9, p < .05, and more likelihood of being abstinent, chi2(1, N = 513) = 18.1, p < .001. Attaining a higher fluoxetine blood level improved the likelihood of completing behavioral treatment and increased the probability of achieving abstinence. PMID- 11764012 TI - Triazolam impairs inhibitory control of behavior in humans. AB - This study tested the effects of the sedative-hypnotic drug triazolam (Halcion) on the ability to inhibit behavior in humans. Thirty adults practiced a stop signal task that measured their ability to inhibit and activate behavioral responses on a choice reaction time task. Equal numbers of participants (i.e., n = 10) then received either 0.25 mg, 0.125 mg, or 0 mg (placebo) of triazolam under double-blind conditions and performed the task intermittently over a 3-hr period. In accord with the hypothesis, triazolam reduced response inhibitions and increased the time required to inhibit a response. The drug also slowed the activation of responses. The findings contribute to the understanding of the basic behavioral mechanisms by which sedative-hypnotic drugs can produce states of behavioral disinhibition in some individuals. PMID- 11764013 TI - Exposure to novel environmental stimuli decreases amphetamine self-administration in rats. AB - Researchers examined whether exposure to novel environmental stimuli reduces drug self-administration. Rats were trained to self-administer amphetamine on a fixed ratio (FR) 5 schedule of reinforcement and then were exposed to novel stimuli during the session. Responding was significantly decreased with exposure to novelty but returned to baseline levels on intervening nonexposure sessions. In 2 subsequent experiments, rats were exposed to novel plastic objects prior to the session. Immediately following exposure, rats were allowed to self-administer amphetamine on an FR 1 schedule, which was increased gradually to an FR 5 either using predetermined increments or on the basis of performance criteria. Exposure to the novel objects significantly decreased acquisition of amphetamine self administration in both situations. Results suggest that exposure to novel environmental stimuli may be effective at reducing drug self-administration. PMID- 11764014 TI - The impact of alcohol and alcohol expectancies on male perception of female sexual arousal in a date rape analog. AB - The impact of alcohol and alcohol expectancies on men's perception of female sexual arousal and men's ability to discriminate accurately female sexual intentions in a dating situation was examined. In a 2 (alcohol) x 2 (expectancy) balanced placebo design, men were exposed to an audiotape of a date rape and asked to signal when the man should stop making sexual advances. On 4 occasions during the vignette, participants rated how sexually aroused the woman on the tape was at that moment. Relative to controls, participants who consumed alcohol or expected to consume alcohol took significantly longer to identify the inappropriateness of the man's sexual behavior toward his date. Similarly, alcohol participants also rated the woman's arousal level significantly higher at the first 2 refusals. Implications of the results are discussed. PMID- 11764015 TI - Integrating disinhibition and learning risk for alcohol use. AB - In this study the authors tested the acquired preparedness model of problem drinking, which holds that trait disinhibition, defined as neurotic extraversion by C. M. Patterson and J. P. Newman (1993), leads to the biased formation of positive over negative alcohol expectancies. Positive expectancies thus mediate disinhibition's influence on drinking. The authors also hypothesized that disinhibition moderates the expectancy-drinking relationship such that disinhibited individuals are more likely to act on their positive expectancies. In Study 1, positive expectancies both mediated and moderated the disinhibition drinking relationship. In Study 2, learning task results indicated that disinhibited individuals sought reward, even when passive avoidance of punishment was indicated. Study 2 also replicated Study I hypotheses for men but generally not for women. PMID- 11764016 TI - The impact of imagining personalized versus standardized urge scenarios on cigarette craving and autonomic reactivity. AB - A cue-reactivity paradigm was used to investigate the effects of personalizing imagery materials on smokers' reactivity to smoking cues. Cigarette smokers (n = 60) described situations used to create 4 personalized imagery scripts: positive mood/urge, positive mood/no urge, neutral mood/urge, and neutral mood/no urge. Their reactivity to these scripts as well as 4 standardized imagery scripts and 4 personalized scripts of another smoker was assessed. Personalization led to greater vividness, positive mood, and relevance ratings compared with the other 2 script types. Personalization of urge material did not enhance craving beyond that generated by the other 2 script types but did suppress craving under no-urge conditions. Findings stand in contrast to current conceptualizations of craving regarding the proposed impact of personalization on craving and suggest alternative mechanisms by which imagery cues influence craving generation. PMID- 11764017 TI - Parental alcoholism and the effects of alcohol on mediated semantic priming. AB - In this study, researchers tested the effects of a moderate dose of alcohol on the spread of activation of associated information in memory using a mediated semantic priming task in which target words are preceded by primes that are either unrelated or indirectly related to the target. Male and female participants with or without a parental history (PH+ and PH-, respectively) of alcoholism were administered the priming task after consuming alcohol or a placebo beverage. Among PH- individuals, alcohol constrained the spread of activation of associated information, as manifested by a reduced priming effect. In contrast, alcohol enhanced priming effects among PH+ participants, though this latter effect appears to be due to a particularly slow response among these individuals to unprimed words. Results are discussed with regard to theories of alcohol's effects on cognitive processes. PMID- 11764018 TI - The impact of smoking urges on working memory performance. AB - The effect of smoking urges on cognitive performance is relatively short-lived (R. A. Zwaan, R. A. Stanfield, & C. M. Madden, 2000). The authors examined whether this results from the short-lived nature of the elicited urge itself or from practice effects on the cognitive task. Smokers listened to 1 of 2 imagery scripts (urge vs. neutral) and subsequently performed 2 cognitive tasks (math and language comprehension). Exposure to the urge script produced significantly less accurate performance at the onset of the 1st task than exposure to the neutral script, but there was no difference at the onset of the 2nd task. Thus, the quick disappearance of the urge effect seems to be due to the transient nature of the elicited urge itself rather than to practice effects. PMID- 11764019 TI - Effects of methylphenidate and expectancy on performance, self-evaluations, persistence, and attributions on a social task in boys with ADHD. AB - This study examined the effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and persistence of 137 boys with attention-deficit/hyperactivity disorder (ADHD) in a get-acquainted dyadic interaction with a peer, using a balanced-placebo design. Boys in 4 groups administered placebo or MPH crossed with being told they received placebo or MPH interacted with child confederates in experimental situations in which social success and failure were manipulated. In contrast with studies of academic persistence, MPH did not affect boys' task persistence or performance. Boys gave more positive self-evaluations and talked more in the success condition as compared with the failure condition. Boys attributed success to effort and ability and failure to task difficulty, and neither MPH nor expectancy affected this pattern. These findings are consistent with other studies in failing to find debilitating effects of MPH or medication expectancies on ADHD boys' attributions or self-evaluations. PMID- 11764020 TI - Through the preoccupation with new technical developments, physicists have lost sight of the realities of cancer care and statistics. For the proposition. PMID- 11764022 TI - Implementing multiple static field delivery for intensity modulated beams. AB - A clinically oriented two-dimensional intensity-modulated beam delivery method is implemented using multiple static segmented fields, i.e., the "step-and-shoot" approach. Starting with a desired al" intensity distribution, it creates a multiple-level intensity approximation, and then constructs a sequence of segmented fields to deliver the multiple-level intensities using multileaf collimator (MLC) and independent backup jaws. The approach starts with a simple grouping of all the nonzero intensity values into a minimum number of clusters for a user specified deviation tolerance for the ideal plan. The k-means clustering algorithm is then employed to find the optimal levels of intensity that minimize the discrepancies between the ideal and the approximated intensities, without violating the user specified deviation tolerance. The multiple-level intensities are then decomposed into a sequence of machine deliverable segments. Apart from the first segment for each gantry angle, all the other segments are arranged to minimize the total travel distance of the leaves. The first segment covers the entire irradiated area and is used for treatment verification by electronic portal imaging. The implementation issues due to the physical constraints of the MLCs are also addressed. PMID- 11764023 TI - Verification of dynamic intensity-modulated beam deliveries in canine subjects. AB - Our objective in this work was to assess the precision and degree of accuracy with which intensity modulated radiation therapy (IMRT) can deliver highly localized dose distributions to tumors near critical structures using the dynamic sliding window technique. Measurements of dose distribution were performed both in vivo and in vitro using a combination of dosimeters [thermoluminescent dosimeters (TLD's), films, and diodes]. In vivo measurements were performed in two groups of purpose-bred dogs: one receiving four-field three-dimensional (3D) conformal treatment and the other receiving IMRT. The algorithms used in the inverse planning process included the Macro Pencil Beam (MPB) model and Projections onto Convex Sets (POCS). Single beam measurements were performed in phantoms to verify the accuracy of monitor unit settings required for delivering the desired doses. The composite doses from the delivery of the seven beam intensity modulated plans were measured in phantoms and cadavers, Biological end points (spinal cord toxicity and neurologic deficits due to irradiation) were evaluated at the end of one year to determine the spatial accuracy of the IMRT treatments over a fractionated course in live subjects. Results in single beam measurements were used at first to improve the dose calculation and translation algorithms. Results of the measurements for the delivery of all seven beams in phantoms confirmed that the system was capable of accurate spatial and dosimetric IMRT delivery. The in vivo results showed dramatic differences between control and IMRT-treated dogs, with the IMRT group showing no adverse effects and the control animals showing severe spinal cord injuries due to irradiation. The measurements presented in this paper have helped to verify the successful and accurate delivery of IMRT in a clinically related model using the University of Washington Medical Center (UWMC) system. PMID- 11764024 TI - Comprehensive quality assurance for the delivery of intensity modulated radiotherapy with a multileaf collimator used in the dynamic mode. PMID- 11764025 TI - Method of identifying dynamic multileaf collimator irradiation that is highly sensitive to a systematic MLC calibration error. AB - In intensity modulated radiotherapy (IMRT), radiation is delivered in a multiple of multileaf collimator (MLC) subfields. A subfield with a small leaf-to-leaf opening is highly sensitive to a leaf-positional error. We introduce a method of identifying and rejecting IMRT plans that are highly sensitive to a systematic MLC gap error (sensitivity to possible random leaf-positional errors is not addressed here). There are two sources of a systematic MLC gap error: centerline mechanical offset (CMO) and, in the case of a rounded end MLC, radiation field offset (RFO). In IMRT planning system, using an incorrect value of RFO introduces a systematic error ARFO that results in all leaf-to-leaf gaps that are either too large or too small by (2*DeltaRFO), whereas assuming that CMO is zero introduces systematic error DeltaCMO that results in all gaps that are too large by DeltaCMO=CMO. We introduce a concept of the average leaf pair Opening (ALPO) that can be calculated from a dynamic MLC delivery file. We derive an analytic formula for a fractional average fluence error resulting from a systematic gap error of Deltax and show that it is inversely proportional to ALPO; explicitly it is equal to Deltax/(ALPO+ 2 * RFO+ epsilon), in which epsilon is generally of the order of 1 mm and Deltax =2 * Delta RFO + CMO. This analytic relationship is verified with independent numerical calculations. PMID- 11764026 TI - Calibration and quality assurance for rounded leaf-end MLC systems. AB - Multileaf collimator (MLC) systems are available on most commercial linear accelerators, and many of these MLC systems utilize a design with rounded leaf ends and linear motion of the leaves. In this kind of system, the agreement between the digital MLC position readouts and the light field or radiation field edges must be achieved with software, since the leaves do not move in a focused motion like that used for most collimator jaw systems. In this work we address a number of the calibration and quality assurance issues associated with the acceptance, commissioning, and routine clinical use of this type of MLC system. These issues are particularly important for MLCs used for various types of intensity modulated radiation therapy (IMRT) and small, conformal fields. For rounded leaf end MLCs, it is generally not possible to make both the light and radiation field edges agree with the digital readout, so differences between the two kinds of calibrations are illustrated in this work using one vendor's MLC system. It is increasingly critical that the MLC leaf calibration be very consistent with the radiation field edges, so in this work a methodology for performing accurate radiation field size calibration is discussed. A system external to the vendor's MLC control system is used to correct or handle limitations in the MLC control system. When such a system of corrections is utilized, it is found that the MLC radiation field size can be defined with an accuracy of approximately 0.3 mm, much more accurate than most vendor's specifications for MLC accuracy. Quality assurance testing for such a calibration correction system is also demonstrated. PMID- 11764027 TI - Influence of respiration-induced organ motion on dose distributions in treatments using enhanced dynamic wedges. AB - The mean velocity of respiration-induced organ motion in cranio-caudal direction is of the same magnitude as the velocity of the moving jaw during a treatment with an enhanced dynamic wedge. Therefore, if organ motion is present during collimator movement, the resulting dose distribution in wedge direction may differ from that obtained for the static case, i.e., without organ motion. The position as a function of time of the moving jaw has been derived from a log-file generated during each treatment. Parameters for the respiratory cycle and information about respiration-induced motion for organs in the upper abdomen were taken from the literature. Both movements were superimposed and the resulting monitor unit distribution has been calculated in the intrinsic coordinate system of the organ. The deviations from the static case have been studied as a function of wedge angle, amplitude of organ motion, respiratory rate, asymmetry of the respiratory cycle, beam energy, and the dose rate. If an amplitude of 30 mm and a respiratory rate of 10 min(-1) are assumed, the maximum deviation in monitor units is 2.5% for a 10 degees wedge, 7% for a 30 degrees wedge, and 16% for a 60 degrees wedge. Furthermore, a dose distribution for an organ undergoing respiration-induced motion has been generated and we found dose deviations of the same magnitude as calculated with the monitor unit distribution. PMID- 11764028 TI - A maximum-entropy method for the planning of conformal radiotherapy. AB - The maximum entropy method (MEM) is a powerful inverse analysis technique that is used in many fields of science and engineering to perform tasks such as image reconstruction and processing of nuclear magnetic resonance signals. Unlike other methods, MEM naturally incorporates a priori knowledge of the problem into the optimized cost function. This feature is especially important in radiotherapy planning, because some knowledge is usually available about the stage of tumor development and about the prescription doses, including some dose constraints to the surrounding normal organs. Inverse planning is inherently consistent with the ability of MEM to estimate parameters inversely. In this investigation, an entropy function determines the homogeneity of dose distribution in the planning target volume; a least-squares function is added to the maximum entropy function as a constraint to measure the quality of reconstructed doses in organs at risk; and an iterative Newton-Ralphson algorithm searches for the optimization solution. Here we provide two examples that validate this application of MEM and the results were compared with manual plans. Although the examples involve conformal radiotherapy, we think MEM can be adopted to optimize intensity modulated radiation therapy. PMID- 11764029 TI - An iterative EPID calibration procedure for dosimetric verification that considers the EPID scattering factor. AB - There has been an increasing interest in the application of electronic portal imaging devices (EPIDs) to dosimetric verification, particularly for intensity modulated radiotherapy. Although not water equivalent, the phantom scatter factor of an EPID, Spe, is generally assumed to be that of a full phantom, Sp, a slab phantom, Sps, or a mini phantom. This assumption may introduce errors in absolute dosimetry using EPIDs. A calibration procedure that iteratively updates Spe and the calibration curve (pixel value to dose rate) is presented. The EPID (Varian Portal Vision) is irradiated using a 20 x 20 cm2 field with different beam intensities. The initial guess of dose rates in the EPID is calculated from ionization chamber measurements in air, multiplied by Sp or Sps. The calibration curve is obtained by fitting EPID readings from pixels near the beam central axis and dose rates in EPID to a quadratic equation. The Spe is obtained from EPID measurements in 10 X 10 cm2 and 20 x 20 cm2 field and from the calibration curve, and is in turn used to adjust the dose rate measurements and hence the calibration curve. The above procedure is repeated until it converges. The final calibration curve is used to convert portal dose to dose in the slab phantom, using the calibrated Spe, or assuming Spe = Sp or Spe=Sps . The converted doses are then compared with the dose measured using an ionization chamber. We also apply this procedure to off-axis points and study its dependence on the energy spectrum. The hypothesis testing results (on the 95% significance level) indicate that systematic errors are introduced when assuming Spe = Sp or Spe=Sps and the dose calculated using Spe is more consistent with ionization chamber measurements. Differences between Spe and Sps are as large as 2% for large field sizes. The measured relative dose profile at dmax using the EPID agrees well with the measured profile at dmax of the isocentric plane using film in a polystyrene phantom with full buildup and full backup, for open and wedged fields, and for a broad range of field sizes of interest. The dependence of the EPID response on the energy spectrum is removed once the calibration is performed under the same conditions as the actual measurements. PMID- 11764030 TI - Electron dosimetry based on the absorbed dose to water concept: a comparison of the AAPM TG-51 and DIN 6800-2 protocols. AB - The dosimetry protocols DIN 6800-2 and AAPM TG-51, both based on the absorbed dose to water concept, are compared in their theoretical background and in their application to electron dosimetry. The agreement and disagreement in correction factors and energy parameters used in both protocols will be shown and discussed. Measurements with three different types of ionization chambers were performed and evaluated according to both protocols. As a result the perturbation correction factor P(60Co)wall for the Roos chamber was determined to 1.024 +/- 0.5%. PMID- 11764031 TI - Automated seed detection and three-dimensional reconstruction. I. Seed localization from fluoroscopic images or radiographs. AB - An automated procedure for the detection of the position and the orientation of radioactive seeds on fluoroscopic images or scanned radiographs is presented. The extracted positions of seed centers and the orientations are used for three dimensional reconstruction of permanent prostate implants. The extraction procedure requires several steps: correction of image intensifier distortions, normalization, background removal, automatic threshold selection, thresholding, and finally, moment analysis and classification of the connected components. The algorithm was tested on 75 fluoroscopic images. The results show that, on average, 92% of the seeds are detected automatically. The orientation is found with an error smaller than 50 for 75% of the seeds. The orientation of overlapping seeds (10%) should be considered as an estimate at best. The image processing procedure can also be used for seed or catheter detection in CT images, with minor modifications. PMID- 11764032 TI - Automated seed detection and three-dimensional reconstruction. II. Reconstruction of permanent prostate implants using simulated annealing. AB - We present an algorithm, based on simulated annealing, for automatic seed matching and three-dimensional spatial coordinate reconstruction using either three radiographic films or three fluoroscopic images taken from different perspectives. The matching problem is defined in the framework of combinatorial optimization, which allows robust reconstruction in presence of calibration imprecision, patient movements, and isometric distortions. Furthermore, by using a global criterion to select the correct matching, we evade common problems of the three-film method and its variants in presence of noise. The algorithm has been tested on 112 clinical cases and 100 simulated implants and used clinically on more than 100 cases. Simulated implants were reconstructed with an average error of 0.21 mm. For clinical cases, comparison of the precision is performed between results obtained with this new method and results obtained using the three-film technique. Compared to the latter technique, the reconstruction precision was improved in 62% of the clinical cases. PMID- 11764033 TI - CT and MRI derived source localization error in a custom prostate phantom using automated image coregistration. AB - Dosimetric evaluation of completed brachytherapy implant procedures is crucial in developing proper technique. Additionally, accurate dosimetry may be useful in predicting the success of an implant. Accurate definition of the prostate gland and localization of the implanted radioactive sources are critical to attain meaningful dosimetric data. MRI is recognized as a superior imaging modality in delineating the prostate gland. More importantly, MRI can be used for source localization in postimplant prostates. However, the MRI derived source localization error bears further investigation. We present a useful tool in determining the source localization error as well as permitting the fusion, or coregistration, of selected data from multiple imaging modalities. We constructed a custom prostate phantom of hydrocolloid material precisely implanted with I-125 seeds. We obtained CT, the accepted modality, and MRI scans of the phantom. Subsequently, we developed an automated algorithm that employs a sequential translation of data sets to initially maximize coregistration and minimize error between data sets. This was followed by a noniterative solution for the necessary rotation transformation matrix using the Orthogonal Procrustes Solution. We applied this algorithm to CT and MRI scans of the custom phantom. CT derived source locations had source localization errors of 1.59 mm +/- 0.64. MRI derived source locations produced similar results (1.67 mm +/- 0.76). These errors may be attributed to the image digitization process. PMID- 11764034 TI - Dosimetric study of the new Intersource125 iodine seed. AB - The use of low energy photon emitters for brachytherapy applications, as in the treatment of the prostate or of eye tumors, has significantly increased these last few years. New seed models for 125I have been recently introduced. The aim of this study is to determine the dosimetric parameters as recommended by the AAPM in the TG43 formalism for a new iodine seed design: the InterSource125 (Furnished by IBt, Seneffe, Belgium). Measurements are made with LiF thermoluminescent dosimeters (size of 1 mm3) in solid water phantoms to obtain the dose constant, the radial dose function, and the anisotropy function. The TLDs were calibrated at 6 MV and an energy correction factor of 1.41 has been applied. The same dose parameters are also obtained by Monte Carlo calculations (MCNP4B) in solid water and in liquid water. The radial function was measured at 1, 1.5, 2, 3, 4, 5, 6, and 7 cm and calculated between 0.3 and 7 cm. The anisotropy functions were measured at 2, 3, and 5 cm and calculated between 0.3 and 7 cm. The calculated and the measured TG43 functions for solid water are in excellent agreement. We have then calculated these functions in liquid water to obtain the dosimetric information for clinical applications as per TG43 recommendations. In WTI, the calculated dose rate constant is 0.98+/-1% and the measured value is 1.03 +/- 7 %. The calculated value for water is 1.02+/- 1 %. In conclusion, the dosimetric functions for the new iodine seed InterSource125 have been determined. They are quite different from the data of the well-known model 6711 from Amersham due to the absence of silver in the new seed. The characteristics are very similar to those of model 6702. PMID- 11764035 TI - Discretizing large traceable vessels and using DE-MRI perfusion maps yields numerical temperature contours that match the MR noninvasive measurements. AB - The success of hyperthermia treatments is dependent on thermal dose distribution. However, the three-dimensional temperature distribution remains largely unknown. Without this knowledge, the relationship between thermal dose and outcome is noisy, and therapy cannot be optimized. Accurate computations of thermal distribution can contribute to an optimized therapy. The hyperthermia modeling group in the Department of Radiotherapy, University Medical Center Utrecht devised a Discrete Vasculature [Kotte et al., Phys. Med. Biol. 41, 865-884 (1996)] model that accounts for the presence of vessel trees in the computational domain. The vessel tree geometry is tracked using magnetic resonance (MR) angiograms to a minimum diameter between 0.6 and 1 mm. However, smaller vessels (0.2-0.6 mm) are known to account for significant heat transfer. The hyperthermia group at Duke University Medical Center has proposed using perfusion maps derived from dynamic-enhanced magnetic resonance imaging to account for the tissue perfusion heterogeneity [Craciunescu et al., Int. J. Hyperthermia 17, 221-239 (2001)]. In addition, techniques for noninvasive temperature measurements have been devised to measure temperatures in vivo [Samulski et al., Int. J. Hypertherminal, 819-829 (1992)]. In this work, a patient with high-grade sarcoma has been retrospectively modeled to determine the temperature distribution achieved during a hyperthermia treatment. Available for this model were MR depicted geometry, angiograms, perfusion maps, as necessary for accurate thermal modeling, as well as MR thermometry data for validation purposes. The vasculature assembly through modifiable potential program [Van Leeuwen et al., IEEE Trans. Biomed. Eng. 45, 596-604 (1998)] was used in order to incorporate the traceable large vessels. Temperature simulations were made using different approaches to describe perfusion. The simulated cases were the bioheat equation with constant perfusion rates per tissue type, perfusion maps alone, tracked vessel tree and perfusion maps, and generated vessel tree. The results were compared with MR thermometry data for a single patient data set, concluding that a combination between large traceable vessels and perfusion map yields the best results for this particular patient. The technique has to be repeated on several patients, first with the same type of malignancy, and after that, on patients having malignancies at other different sites. PMID- 11764036 TI - Relationship between phantom failure rates and radiation dose in mammography accreditation. AB - The American College of Radiology Mammography Accreditation Program (ACR MAP) reviews both clinical mammograms and a phantom image to assess clinical and technical quality from each mammography unit. The phantom contains details representing fibers (speculations), speck groups (microcalcifications), and masses. The depiction of these structures by the mammographic system is scored by medical physicists. The phantom image is taken using the facility's exposure technique for a 4.2-cm thick breast of average composition. The mean glandular dose (MGD) is determined from a set of thermoluminescent dosimeters placed on top of the chest wall edge of the phantom. Phantom scores and MGD data collected from 1993 to 1999 based on 31 535 unit evaluations are presented in this paper. The relationship between the failure rate for phantom image quality and MGD has been analyzed. While over all doses the phantom failure rate was 11%, for doses of 0.26 to 0.50 mGy the failure rate was 43%. The phantom failure rate fell continuously to about 6% for MGDs in the range of 1.51-2.0 mGy. With further increases in dose, failure rates began to rise. Factors that may account for these results are presented and discussed. PMID- 11764037 TI - Performance gain in computer-assisted detection schemes by averaging scores generated from artificial neural networks with adaptive filtering. AB - The authors investigated a new method to optimize artificial neural networks (ANNs) with adaptive filtering used in computer-assisted detection schemes in digitized mammograms and to assess performance changes when averaging classification scores from three sets of optimized schemes. Two independent training and testing image databases involving 978 and 830 digitized mammograms, respectively, were used in this study. In the training data set, initial filtering and subtraction resulted in the identification of 592 mass regions and 3790 suspicious, but actually negative regions. These regions (including both true-positive and negative regions) were segmented into three subsets three times based on the calculation of the values of three features as segmentation indices. The indices were "mass" size multiplied by their digital value contrast, conspicuity, and circularity. Nine ANN-based classifiers were separately optimized using a genetic algorithm for each subset of regions. Each region was assigned three classification scores after applying the three adaptive ANNs. The performance gain of the CAD scheme after averaging the three scores for each suspicious region was tested using an independent data set and a ROC methodology. The experimental results showed that the areas under ROC curves (Az) for the testing database using three sets of optimized ANNs individually were 0.84+/ 0.01, 0.83+/-0.01, and 0.84+/-0.01, respectively. The between-index correlations of three A values were 0.013, -0.007, and 0.086. Similar to averaging diagnostic ratings from independent observers, by averaging three ANN-generated scores for each testing region, the performance of the CAD scheme was significantly improved (p<0.001) with Az value of 0.95+/-0.01. PMID- 11764038 TI - Analysis of temporal changes of mammographic features: computer-aided classification of malignant and benign breast masses. AB - A new classification scheme was developed to classify mammographic masses as malignant and benign by using interval change information. The masses on both the current and the prior mammograms were automatically segmented using an active contour method. From each mass, 20 run length statistics (RLS) texture features, 3 speculation features, and 12 morphological features were extracted. Additionally, 20 difference RLS features were obtained by subtracting the prior RLS features from the corresponding current RLS features. The feature space consisted of the current RLS features, the difference RLS features, the current and prior speculation features, and the current and prior mass sizes. Stepwise feature selection and linear discriminant analysis classification were used to select and merge the most useful features. A leave-one-case-out resampling scheme was used to train and test the classifier using 140 temporal image pairs (85 malignant, 55 benign) obtained from 57 biopsy-proven masses (33 malignant, 24 benign) in 56 patients. An average of 10 features were selected from the 56 training subsets: 4 difference RLS features, 4 RLS features, and 1 speculation feature from the current image, and 1 speculation feature from the prior, were most often chosen. The classifier achieved an average training Az of 0.92 and a test Az of 0.88. For comparison, a classifier was trained and tested using features extracted from the 120 current single images. This classifier achieved an average training Az of 0.90 and a test Az of 0.82. The information on the prior image significantly (p = 0.015) improved the accuracy for classification of the masses. PMID- 11764039 TI - A fast and efficient method for sequential cone-beam tomography. AB - Sequential cone-beam tomography is a method that uses data of two or more parallel circular trajectories of a cone-beam scanner to reconstruct the object function. We propose a condition for the data acquisition that ensures that all object points between two successive circles are irradiated over an angular span of the x-ray source position of exactly 360 degrees in total as seen along the rotation axis. A fast and efficient approximative reconstruction method for the proposed acquisition is presented which uses data from exactly 360 degrees for every object point. It is based on the Tent-FDK method which was recently developed for single circular cone-beam CT. The measurement geometry does not provide sufficient data for exact reconstruction but it is shown that the proposed reconstruction method provides satisfying image quality for small cone angles. PMID- 11764040 TI - Comparison of an amorphous silicon/cesium iodide flat-panel digital chest radiography system with screen/film and computed radiography systems--a contrast detail phantom study. AB - Flat-panel (FP) based digital radiography systems have recently been introduced as a new and improved digital radiography technology; it is important to evaluate and compare this new technology with currently widely used conventional screen/film (SF) and computed radiography (CR) techniques. In this study, the low contrast performance of an amorphous silicon/cesium iodide (aSi/Csl)-based flat panel digital chest radiography system is compared to those of a screen/film and a computed radiography system by measuring their contrast-detail curves. Also studied were the effects of image enhancement in printing the digital images and dependence on kVp and incident exposure. It was found that the FP system demonstrated significantly better low-contrast performance than the SF or CR systems. It was estimated that a dose savings of 70%-90% could be achieved to match the low-contrast performance of the FP images to that of the SF images. This dose saving was also found to increase with the object size. No significant difference was observed in low-contrast performances between the SF and CR systems. The use of clinical enhancement protocols for printing digital images was found to be essential and result in better low-contrast performance. No significant effects were observed for different kVps. From the results of this contrast-detail phantom study, the aSi/CsI-based flat-panel digital chest system should perform better under clinical situations for detection of low-contrast objects such as lung nodules. However, proper processing prior to printing would be essential to realizing this better performance. PMID- 11764041 TI - Decaying source method for scintillation camera resolving times. AB - An earlier paper by the author showed that scintillation camera systems can be described effectively using the resolving times T and tau0 of the dominant nonparalyzable and paralyzable components, that is, the detector system and the computer interface, respectively. When used with a full spectrum window, the camera has a lower nonparalyzable and an upper paralyzable operating range with normalized threshold input rate n(t)= N(t)tau(0) = ln(1 +k(T)n(t)), where kT= T/(tau)0. Correct determination of T and tau(0) requires that both r12 and r in the normalized two-source equations kT=(2/r12- 1/r) and k0=(r12/2r2)ln(2r/r12) come from the nonparalyzable (n< or =n(t)) and paralyzable (n> or =n(t)) ranges, respectively. A serious constraint of the two-source method, therefore, is that the large ratio a = n12 ln = 2 can lead to an input rate range (n,n12), which includes the threshold point n,, and in which neither T nor tau0 can be measured correctly. The decaying source method constitutes a refinement of the two-source method, which enables smaller ratios 1 5, OR 2.09 (95% CI 1.07, 4.09). They were significantly more likely to have hypotension, 35.5 versus 22.3%, OR 1.90 (95% CI 1.01, 3.59). There was no difference in the frequency of respiratory distress syndrome, mechanical ventilation, infection or rate of congenital malformation. Mortality before hospital discharge was significantly greater for the SGA infant (52.6 versus 28.4%, OR 2.79 (95% CI 1.56, 5.02)). This difference remained significant after exclusion of congenital abnormalities. Survivors had a longer mean duration of stay, (54.4 versus 41.2 days, p < 0.001). CONCLUSION: The higher mortality seen in SGA infants appears to be due to a poorer condition at birth. There is no evidence that SGA infants have more mature lungs so antenatal corticosteroids should not be withheld on these grounds. PMID- 11764053 TI - Disability and handicap among elderly Singaporeans. AB - Singapore's elderly population has been growing rapidly and is expected to constitute more than 25 percent of the total population by the year 2030. The ageing process brings with it a host of health problems. Here the question arises -Are the increasing years of life going to create a high proportion of sick and disabled elderly people, or a rich human resource of healthy senior citizens? Since more women are living longer than men, who would face a higher risk of disability and handicap? These questions are yet to be answered in Singapore. This paper seeks answers to these questions. The study is based on a sample survey of 1209 elderly Singaporeans living in Kampong Glam, Kreta Ayer and Bukit Merah parliamentary constituencies which have some of the highest proportions of the aged population. The results revealed that more than half of the aged had a disability and the rate of disability was significantly higher among the women as compared to the men. More than one-third of the elderly had a handicap and the rate of handicap among the women was twice as much as that among the men. Severity of handicap was directly correlated with age. PMID- 11764054 TI - Rhabdomyolysis and acute renal failure following a switchover of therapy between two fibric acid derivatives. AB - Drug induced myopathy has been reported with the use of fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and nicotinic acid. Over the last three decades, hypolipemiants like fibric acid derivatives and statins have been increasingly recognised as causes of rhabdomyolysis and acute renal failure especially during combination therapy and in the presence of underlying renal impairment. We report two cases of bezafibrate-induced rhabdomyolysis in patients with underlying coronary artery disease and pre existing renal impairment. Both patients developed rhabdomyolysis leading to acute renal failure soon after their hyperlipidaemia treatment was changed from gemfibrozil to bezafibrate. There were no intercurrent illnesses or co administration of other lipid lowering drugs in both patients. Even though both drugs belong to the same fibric acid derivatives group, these patients developed the complication only after a switchover of therapy. PMID- 11764055 TI - Occupational asthma in Singapore. AB - AIM: Since the first notified case of occupational asthma in 1983, a total of 90 cases were confirmed as on 31st December 1999. In this study, demographic data, causative agents and impact on the workers were described. METHODS: The data was derived from notifications to the Ministry of Manpower and referrals to the Occupational Lung Disease Clinic jointly run with Department of Respiratory Medicine, Tan Tock Seng Hospital. RESULTS: Of the 90 cases, 19 (21%) were females and 71 (79%) were males. There were 48 (53%) Chinese, 22 (24%) Malays, 14 (16%) Indians and 6 (7%) of other ethnic origins. The mean age at diagnosis was 35.8 +/ 9.3 yrs. The mean duration of exposure prior to onset of symptoms was 34.9 +/- 57.3 months. The most common causative agent was isocyanates (28 cases, 31%) followed by solder flux (12 cases, 13%) and welding fumes (8 cases, 9%) respectively. Thirteen (14.4%) workers were assessed to have permanent disability under the Workmen's Compensation Act. CONCLUSIONS: Since 1990, occupational asthma has overtaken silicosis and asbestosis as the most common occupational lung disease in Singapore. The most common causative agent is isocyanates. Occupational asthma is a condition associated with disability in the workplace and may still be largely under-reported. PMID- 11764056 TI - Case report of a granular cell tumour in the nasal septum of a child. AB - A six-year-old child with a nasal septal polyp presents with pain and nasal discharge. The diagnosis of a granular cell tumour was made histologically on excision of the polyp. This interesting case of an uncommon lesion presenting in a relatively rare paediatric age group is, as far as we know, the first report of a granular cell tumour involving the nasal septum. PMID- 11764057 TI - Gastrointestinal manifestations of systemic lupus erythematosus. AB - Gastrointestinal symptoms are common in patients with systemic lupus erythematosus (SLE) and can be due to primary gastrointestinal disorders, complications of therapy or SLE itself. In this case report, we describe three different presentations and causes of gastrointestinal complaints in patients with SLE. Diagnostic and management problems are discussed. PMID- 11764058 TI - Proteinuria: clinical signficance and basis for therapy. AB - Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure. PMID- 11764059 TI - Clinics in diagnostic imaging (64). Invasive pulmonary aspergillosis. AB - A 30-year-old woman undergoing chemotherapy for acute myeloid leukemia developed fever. Chest radiograph showed ill-defined nodules in the mid and lower zones. CT showed multiple nodules that cavitated with commencement of anti-fungal therapy. Follow-up CT showed complete resolution of the pulmonary nodules, confirming the diagnosis of invasive pulmonary aspergillosis. Aspergillus fumigatus presents clinically as aspergilloma, invasive pulmonary aspergillosis or allergic bronchopulmonary aspergillosis depending on the immune status of the host. The different manifestations are discussed and imaging features of representative clinical case studies are illustrated. PMID- 11764060 TI - Cortical blindness following coronary angiography. PMID- 11764061 TI - Cognitive behavior therapy for somatization disorder: a preliminary investigation. AB - Patients diagnosed with somatization disorder have high rates of disability and often prove refractory to treatment. This preliminary investigation examines the effect of a 10-session cognitive behavior therapy (CBT) protocol on the physical discomfort and disability of severely impaired somatizers. The severity of patients' physical discomfort and disability was assessed at baseline, post treatment, and eight months following treatment. Patients reported significant improvement in symptomatology and physical functioning between baseline and post treatment as well as between baseline and follow-up. The findings suggest that CBT might benefit patients diagnosed with somatization disorder and should be subjected to a controlled treatment trial. PMID- 11764062 TI - Reliability, validity, and normative data of the Penn State Worry Questionnaire in 8-12-yr-old children. AB - The Penn State Worry Questionnaire for Children (PSWQ-C) is a 14-item self-report questionnaire that intends to measure the tendency of children to engage in excessive, generalized, and uncontrollable worry (Chorpita et al., Behav. Res. Ther. 35 (1997) 569-581). The current study further examined the reliability and validity of the PSWQ-C in a large sample of 8-12-yr-old children (N = 486). Psychometric evaluation indicates that it is preferable to discard the three reverse scored items from the PSWQ-C when using the measure in this particular age group. The shortened 11-item PSWQ-C turned out to be reliable in terms of internal consistency and correlated meaningful with a scale measuring anxiety disorders symptoms. That is, PSWQ-C scores were significantly associated with all types of anxiety disorders symptoms but in particular with symptoms of generalized anxiety disorder. Normative data of the PSWQ-C are provided against which scores of individual children in this age range can be compared. PMID- 11764063 TI - Interapy, treatment of posttraumatic stress through the Internet: a controlled trial. AB - On-line therapy offers many advantages over face-to-face settings. Interapy includes psycho-education, screening, effect measures and protocol-driven treatment via the Internet for clients. The present paper reports the results of a controlled trial on the Interapy treatment of posttraumatic stress and grief in students, gaining course credits. The participants in the experimental condition (n = 13) improved significantly than the participants in the waiting-list control condition (n = 12), on trauma-related symptoms and general psychopathology. The effect sizes were large. Eighty percent of the treated participants showed clinically significant improvement after treatment. The possibilities for future research with Interapy, including studies into moderating variables, are discussed. PMID- 11764064 TI - Cognitive and biochemical processes in depressed adult outpatients: a test of the circular process model. AB - The circular process model is a psychobiological model of depression, in which it is postulated that catecholamines and negative cognitions interact to influence depression. Since its publication, there have been no empirical tests to support or refute the model. This study tested the model in 92 depressed adult outpatients with non-bipolar non-psychotic depression. There were no significant bivariate correlations among the biochemical and cognitive measures. However, the interactive model was supported by results of two out of three hierarchical regression analyses, in which the biochemical-by-cognitive interactive terms significantly predicted depression after the main effects of each variable were accounted for. These findings show sufficient evidence in support of the Circular Process Model to warrant further testing over the treatment period. PMID- 11764065 TI - Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia: one disease or three? PMID- 11764066 TI - Nishot: on target, but there's no magic bullet. PMID- 11764067 TI - Current status of HER2 testing: caught between a rock and a hard place. PMID- 11764068 TI - Lymphoma transformation: genetic relatedness, stealth lymphomas, and the final frontier. PMID- 11764069 TI - Pathologists' assistants practice: a measurement of performance. AB - Despite their widespread utilization, little is known about the quality of pathologists' assistants' services. Pathologists' assistants' performance was compared with pathology residents' performance using the metrics of lymph node retrieval and tissue resubmission rates. Lymph node retrieval was calculated by retrospective review of surgical pathology reports from a sample of axillary dissection, mastectomy, and colorectal specimens. Tissue resubmission rates were calculated by retrospective review of a sample of general surgical pathology reports. Pathologists' assistants retrieved a significantly greater total number of lymph nodes compared with pathology residents; however, there was no difference in the total number of positive lymph nodes retrieved. Cases for which pathologists' assistants performed the gross examination had a significantly decreased resubmission rate compared with those performed by residents. In this setting, the gross examination performance of pathologists' assistants was equivalent to or superior to that of pathology residents. These results provide the first information available relating to pathologists' assistants' performance in surgical pathology. PMID- 11764070 TI - Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. AB - To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non-squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas. Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63. Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin. PMID- 11764071 TI - Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct. AB - We immunohistochemically labeled 72 biopsy specimens from the extrahepatic biliary tree and pancreas for Dpc4 protein and correlated expression with histologic diagnosis and patient follow-up. Specimens were classified histologically as follows: nonneoplastic, 35; neoplastic, 22; atypical, 15. Loss of expression of Dpc4 protein was identified in 12 specimens; 11 were histologically diagnostic of carcinoma. The 12th specimen was from a patient whose biopsy specimen initially was diagnosed as "atypical," but clinical follow up revealed adenocarcinoma. Of the 12 atypical biopsy specimens with intact expression for Dpc4, follow-up later revealed that 10 were adenocarcinoma. Loss of expression of Dpc4 protein was never identified in a benign specimen. Immunohistochemical labeling for the Dpc4 gene product is a specific marker of carcinoma in biopsy specimens of the pancreas and extrahepatic bile ducts and is marginally helpful in classifying atypical specimens. The sensitivity for carcinoma is low. This latter finding is not unexpected, because the DPC4 tumor suppressor gene is inactivated in only about half of pancreatic and biliary malignant neoplasms. Importantly, loss of Dpc4 expression has been reported in in situ carcinomas, suggesting that loss of expression should not be equated with invasive carcinoma. PMID- 11764072 TI - Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma. AB - Assessment of angiogenesis may yield important information for an effective antiangiogenic treatment for hepatocellular carcinoma (HCC) because HCC is characteristically hypervascular We examined the relationship of microvessel density (MVD), vascular endothelial growth factor (VEGF), and VEGF receptors Flt 1 and Flk-1/KDR in 50 patients with HCC and in 3 hepatoma cell lines. VEGF messenger RNA (mRNA) was overexpressed in 26 tumors (52%), and the 3 VEGF isoforms (121, 165, and 189) were present in high frequencies. Flt-1 mRNA was overexpressed in 34 tumors (68%), with levels significantly increased in HCCs compared with the nontumorous livers. Tumor Flt-1 mRNA significantly correlated with tumor VEGF mRNA levels. Within the group of tumors 8.5 cm or less in diameter, tumors with intrahepatic metastasis in the form of tumor microsatellite formation had significantly higher VEGF mRNA levels. MVD assessed by immunohistochemical analysis with CD34 antibody was inversely related to tumor size. Angiogenesis as assessed by MVD and tumor VEGF expression seems to have a more important role in tumor growth and intrahepatic metastasis in smaller HCCs. The differential up-regulation of Flt-1 suggests that it may have an important role in angiogenesis in HCC. PMID- 11764073 TI - Portal tract eosinophils and hepatocyte cytokeratin 7 immunoreactivity helps distinguish early-stage, mildly active primary biliary cirrhosis and autoimmune hepatitis. AB - We studied nondiagnostic liver biopsy specimens from 20 patients with definite primary biliary cirrhosis (PBC) and 18 with definite autoimmune hepatitis (AIH) to identify distinguishing features. All patients had early-stage disease; biopsy specimens were devoid of granulomas or diagnostic features of PBC or AIH. Diagnoses were based on serologic and clinical variables. Sixteen specimens from each group were immunostained with cytokeratin 7. The density of portal tract eosinophils and number with cytokeratin 7-reactive periportal hepatocytes were quantified. Sixteen of 18 patients with AIH and 13 of 20 with PBC had no or minimal bile duct injury. Histologic activity index scores were 5.8 in AIH and 5.7 in PBC. The mean portal eosinophil score was greater in PBC than in AIH. Cytokeratin 7 identified many central bile ducts that were obscured by portal inflammation. The mean periportal cytokeratin 7-reactive hepatocyte score was greater in PBC than in AIH. Portal eosinophils and cytokeratin 7 reactivity in periportal hepatocytes are supportive of PBC rather than AIH. No morphologic features were supportive of AIH. Cytokeratin 7 reactivity in periportal hepatocytes may be an early response to PBC-induced biliary obstruction in other regions of the liver. PMID- 11764074 TI - Juxtaglomerular cell tumor: a clinicopathologic study of four cases and review of the literature. AB - We studied 4 new cases of juxtaglomerular cell tumor and compared their morphologic and immunohistochemicalfeatures with 2 renal hemangiopericytomas and 5 cutaneous glomus tumors. The juxtaglomerular tumors were resectedfrom 2 males and 2 females (mean age at diagnosis, 23 years). Three patients manifested with severe hypertension. Tumors ranged from 2.2 to 8.0 cm and were well circumscribed. The tumors consisted of solid sheets and nodules of variably sized tumor cells with round, oval, and spindled nuclei alternating with edematous microcystic foci. Nuclear atypia, present in all tumors, was a prominent feature in 2. Mitotic activity was not identified. All cases showed hemorrhage, numerous mast cells, and thick-walled blood vessels. Unusual features included coagulative tumor necrosis, a hemangiopericytoma-like vascular pattern, and hyalinized stroma. All tumors were immunoreactive for CD34 and actin. Ultrastructural analysis revealed the presence of rhomboid-shaped renin protogranules. Patients were treated by partial or radical nephrectomy and followed up for 14 to 48 months. There were no recurrences or metastases. The characteristic clinical and morphologic features of juxtaglomerular cell tumor permit distinction from renal hemangiopericytoma and other renal tumors. PMID- 11764075 TI - The relative importance of anatomic and PSA factors to outcomes after radical prostatectomy for prostate cancer. AB - We report on how anatomic pathology observations and prostate-specific antigen (PSA) observations made before and just after radical prostatectomy relate to subsequent outcomes in men with prostate cancer. Our study patients consisted of more than 200 men who underwent radical prostatectomy and who had a mean follow up of more than 6 years. We found that there were 2 categories of failures after surgery--one consisting of an eventual elevated PSA level and the other consisting of an early death from progressive tumor--and that these 2 failures related differently to PSA and anatomic pathology observations made at the time of prostatectomy. Whereas preoperative and postoperative levels of PSA related most closely to PSA failure, Gleason grade 5 and the percentage carcinoma related most closely to early death. Our results suggest how men could be sorted into 3 prognostic categories after surgery: one with high hazard for early death, a second with low hazard for early death but with high probability for eventual elevated PSA level, and a third with overall good prognosis. PMID- 11764076 TI - Safely reducing manual urine microscopy analyses by combining urine flow cytometer and strip results. AB - We aimed to reduce the number of manual urine microscopy examinations safely by cross-interpretation of the Sysmex UF-100 (TOA Medical Electronics, Kobe, Japan) and urine strip results such that microscopy would be performed if there was discordance between the UF-100 and urine strip results. We also evaluated the usefulness of the optional UF-100 expert software. We performed 2 studies: study 1 to establish review rules for eventual microscopic examination; study 2, a validation study. Our review rates were 40% and 48% and those of UF-100 software were 16% and 32% for the 2 studies. Our false-positive and false-negative results, among the samples not flagged for microscopic review, were acceptably low. We did not find a good correlation between the microscopic classification of RBC morphologic features and the classification given by the UF-100. Since incorporation of the automated urine strip reader and the UF-100 in routine use, our manual microscopy has been reduced to less than 40%. PMID- 11764077 TI - The impact of requisition design on laboratory utilization. AB - Laboratory utilization by clinician specialty groups serving outpatients was monitored before and after requisition redesign. Requisition changes were designed to address compliance and utilization issues and included implementation of test groupings and cascades or ordering algorithms. Data collected included the number of selected tests and test sets ordered during both time intervals and the number of patient office visits. Selected tests for monitoring included CBC counts, metabolic panels, thyroid function tests, hepatic function tests, urine analysis, and send-out testing. Statistical significance was measured using Poisson rates for test ordering. The composite effect was a significant decrease in the overall number of tests ordered per outpatient visit for most specialties, with a shift in ordering practices from panels to individual tests. Utilization rates by specialty groups were characterized by average number of laboratory tests ordered per patient visit. PMID- 11764078 TI - Cytogenetic findings in mantle cell lymphoma cases with a high level of peripheral blood involvement have a distinct pattern of abnormalities. AB - We compared conventional cytogenetic findings in mantle cell lymphomas (MCLs) having an absolute peripheral lymphocytosis of more than 10,000/microL (>10 x 10(9)/L) at diagnosis ("leukemic"; n = 30) with those in cases having no or minimal lymphocytosis ("nodal"; n = 19). Only cases positive for t(11;14) were included for study. Forty-six cases (94%) had abnormalities in addition to t(11;14). The most frequent abnormalities involved chromosome 13 (26 cases [53%]), followed by chromosomes 1, 3, 7, 8, 9, 10, 12, 15, 17, and 21 (11-18 cases [22%-37%]). There was no difference in the number of aberrations between the 2 groups. Abnormalities of chromosomes 17, 21, and 22 were more frequent, and breakpoints involving 8q24, 9p22-24, and 16q24 were found exclusively in leukemic MCL. Chromosome 17 aberrations involved were structural (breakpoints involving 17p13, 17p11.2, 17q) in leukemic MCL but were only numeric in nodal MCL. Thus, leukemic MCL differs from nodal MCL in their cytogenetic profiles, which may contribute to the clinical presentation. PMID- 11764079 TI - Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma. AB - Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many morphologic and immunophenotypic features. In addition to histomorphologic examination, it is customary to use the absence of CD23 to differentiate MCL from CLL/SLL, based primarily on reported comparisons of immunohistochemical staining of tissue sections. These findings are widely extrapolated to flow cytometric analysis, although available data are contradictory and not sufficiently detailed. We compared expression of CD23 by flow cytometry in 22 cases of MCL and 25 cases of CLL/SLL. Lymphoma cells in 12 of 22 MCLs were negative for CD23, and 10 showed dim expression. In contrast, none of 25 CLL/SLLs were negative for CD23, 4 were dimly positive, and 21 were moderately or brightly positive. Thus, a significant proportion of MCL exhibited overlap of CD23 expression in the low-intensity range with CLL/SLL. Clinically, there was no correlation between the intensity of CD23 expression and clinical stage at diagnosis or survival. These findings emphasize that by flow cytometry, MCL can be differentiated reliably from CLL/SLL using CD23 if negative expression is observed. However, with dimly positive expression, interpretation should be cautious. PMID- 11764080 TI - Primary diagnosis of whipple disease manifesting as lymphadenopathy: use of polymerase chain reaction for detection of Tropheryma whippelii. AB - Whipple disease is a rare, chronic multisystem disease associated with the recently characterized organism Tropheryma whippelii. Extraintestinal manifestation involving the central nervous system, heart, and joints occasionally occurs. Involvement of the abdominal lymph nodes, especially the mesenteric and periaortic nodes, is not uncommon. However, peripheral lymphadenopathy as the sole clinical manifestation of Whipple disease is rare. We describe 2 patients with Whipple disease whose initial manifestation was lymphadenopathy. Lymph nodes from both patients showed infiltration of the sinuses by macrophages containing periodic acid-Schiff-positive, diastase resistant, sickle-like structures. Electron microscopic evaluation confirmed the presence of rod-like organisms. DNA from each sample was amplified by the polymerase chain reaction using a specific set of oligonucleotide primers developed against the 16S ribosomal RNA coding sequence of T. whippelii. The histopathologic features and differential diagnosis of lipogranulomatous lymphadenopathy secondary to Whipple disease, as well as use of molecular-based assays, are discussed. PMID- 11764081 TI - Laboratory, morphologic, and immunophenotypic correlates of surface immunoglobulin heavy chain isotype expression in B-cell chronic lymphocytic leukemia. AB - We compared surface immunoglobulin heavy chain isotype expression with a number of laboratory, morphologic, and immunophenotypic features in a series of 76 cases of B-cell chronic lymphocytic leukemia (B-CLL). Fifty-five cases were IgM+/IgD+, a phenotype associated with antigenically naive B cells; 16 cases expressed IgD without IgM, a phenotype seen in a subset of normal B cells with extensive somatic immunoglobulin variable region (IgV) gene mutations; and 5 cases were IgD , a phenotype associated with memory B cells. WBC count, atypical morphologic features, atypical immunophenotypic characteristics, and CD38 expression were nonrandomly distributed among the 3 categories of heavy chain isotype expression. Moreover, a WBC count more than 30,000/microL (30 x 10(9)/L), atypical morphologic features, and CD38 expression in more than 30% of neoplastic cells (all adverse prognostic factors in B-CLL) were less common among IgD-only cases than among IgM+/IgD+ and IgD- cases. These data demonstrate that surface immunoglobulin heavy chain isotype expression is associated with several laboratory, morphologic, and immunophenotypic features in B-CLL. The subset of B CLL with the IgD-only phenotype is associated with several favorable prognostic factors, suggesting the possibility that IgD-only B-CLL may be associated with a favorable prognosis. PMID- 11764082 TI - Automated quantitation of hemoglobin-based blood substitutes in whole blood samples. AB - It is necessary to develop methods for accurate monitoring of cell-free hemoglobin in circulation. Routine monitoring of circulating cell-free hemoglobin will be useful for evaluating the efficacy of blood substitute administration andfor determining the clearance rates of the blood substitute from circulation. In addition, discriminating between cell-free hemoglobin and cell-associated hemoglobin will enable accurate determination of RBC indices, mean cell hemoglobin and mean corpuscular hemoglobin concentration, in individuals receiving hemoglobin-based blood substitutes. As colorimetric methods used by hematology analyzers to quantitate the hemoglobin value of a blood sample cannot distinguish between cell-associated and cell-free hemoglobin, it is currently not feasible to quantitate the levels of hemoglobin substitutes in circulation. The advent of a technology that measures volume and hemoglobin concentration of individual RBCs provides an alternative strategy for quantitating the cell associated hemoglobin in a blood sample. We document that the combined use of cell-based and colorimetric hemoglobin measurements provides accurate discrimination between cell-associated and cell-free hemoglobin over a wide range of hemoglobin levels. This strategy should enable rapid and accurate monitoring of the levels of cell-free hemoglobin substitutes in the circulation of recipients of these blood substitutes. PMID- 11764083 TI - Comparison of touch imprints with aspirate smears for evaluating bone marrow specimens. PMID- 11764084 TI - Induction of CD13 antigen in in vitro culture and assessment of negative or positive in acute myeloid leukemia cases. PMID- 11764085 TI - Update on the neuropathological diagnosis of frontotemporal dementias. PMID- 11764086 TI - Regulation of Th1 and Th2 lymphocyte migration by human adult brain endothelial cells. AB - Endothelial cells of the blood-brain barrier (BBB) have the ability to regulate and restrict the passage of cells and molecules from the periphery to the CNS. We have used an in vitro assay of lymphocyte migration across monolayers of human adult brain endothelial cells (HBEC) as a model of lymphocyte migration across the BBB. We found that human allogeneic or MBP-reactive Th2-polarized lymphocytes migrate more avidly than Th1-polarized lymphocytes. Migration of Th2 but not Th1 cells across brain endothelium was inhibited by antibodies directed at MCP-1, a chemokine produced by HBECs. We could detect CCR2, a chemokine receptor that recognizes MCP-1 on Th2 but not Th1 lymphocytes. ICAM-1 and VCAM-1 molecules were expressed on the surface of HBECs under basal conditions and were upregulated by Th1 but not Th2 cell-derived supernatants. Migration of both lymphocyte subsets was dependent on LFA-1/ICAM-1 interactions. Blocking VLA-4/VCAM-1 binding did not influence actual trans-endothelial migration. These results suggest that HBECs composing the BBB favor the migration of Th2 cells. We postulate that this selectivity may help prevent activated Th1 lymphocytes, the putative CNS autoimmune disease initiating cells, from reaching the CNS parenchyma and favor entry of Th2 cells, a putative means to induce bystander suppression in the CNS. PMID- 11764087 TI - Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures. AB - We report clinical, neuropathologic and molecular genetic data from an individual affected by a familial Alzheimer disease (AD) variant. The proband had an onset of dementia at age 29 followed by generalized seizures a year later. He died at age 40. Neuropathologically, he had severe brain atrophy and characteristic histopathologic lesions of AD. Three additional neuropathologic features need to be emphasized: 1) severe deposition of Abeta in the form of diffuse deposits in the cerebral and cerebellar cortices, 2) numerous Abeta deposits in the subcortical white matter and in the centrum semiovale, and 3) numerous ectopic neurons, often containing tau-immunopositive neurofibrillary tangles, in the white maner of the frontal and temporal lobes. A molecular genetic analysis of DNA extracted from brain tissue of the proband revealed a S169L mutation in the Presenilin 1 (PSEN1) gene. The importance of this case lies in the presence of ectopic neurons in the white matter, early-onset seizures, and a PSEN1 mutation. We hypothesize that the PSEN1 mutation may have a causal relationship with an abnormality in neuronal development. PMID- 11764088 TI - Inhibition of sorbitol dehydrogenase exacerbates autonomic neuropathy in rats with streptozotocin-induced diabetes. AB - We have developed an animal model of diabetic autonomic neuropathy that is characterized by neuroaxonal dystrophy (NAD) involving ileal mesenteric nerves and prevertebral sympathetic superior mesenteric ganglia (SMG) in chronic streptozotocin (STZ)-diabetic rats. Studies with the sorbitol dehydrogenase inhibitor SDI-158, which interrupts the conversion of sorbitol to fructose (and reactions dependent on the second step of the sorbitol pathway), have shown a dramatically increased frequency of NAD in ileal mesenteric nerves and SMG of SDI treated versus untreated diabetics. Although lesions developed prematurely and in greater numbers in SDI-treated diabetics, their distinctive ultrastructural appearance was identical to that previously reported in long-term untreated diabetics. An SDI effect was first demonstrated in the SMG of rats that were diabetic for as little as 5 wk and was maintained for at least 7.5 months. As in untreated diabetic rats, rats treated with SDI i) showed involvement of lengthy ileal, but not shorter, jejunal mesenteric nerves; ii) demonstrated NAD in paravascular mesenteric nerves distributed to myenteric ganglia while sparing adjacent perivascular axons ramifying within the vascular adventitia; and, iii) failed to develop NAD in the superior cervical ganglia (SCG). After only 2 months of SDI-treatment, tyrosine hydroxylase immunolocalization demonstrated marked dilatation of postganglionic noradrenergic axons in paravascular ileal mesenteric nerves and within the gut wall versus those innervating extramural mesenteric vasculature. The effect of SDI on diabetic NAD in SMG was completely prevented by concomitant administration of the aldose reductase inhibitor Sorbinil. Treatment of diabetic rats with Sorbinil also prevented NAD in diabetic rats not treated with SDI. These findings indicate that sorbitol pathway-linked metabolic imbalances play a critical role in the development of NAD in this model of diabetic sympathetic autonomic neuropathy. PMID- 11764089 TI - Oligodendroglial tumors frequently demonstrate hypermethylation of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes. AB - We investigated 34 oligodendroglial tumors (7 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas) for deletion, mutation, hypermethylation, and expression of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes at 9p21. One anaplastic oligoastrocytoma carried a homozygous deletion including all 3 genes. None of the tumors demonstrated point mutations in any of the genes. Methylation-specific polymerase chain reaction (MSP) analysis and sequencing of bisulfite-modified DNA, however, revealed frequent hypermethylation of the 5'-CpG islands in CDKN2A, p14ARF, and CDKN2B. Partial or complete methylation of the majority of CpG sites analyzed from each gene was detected in 32% of the tumors at the CDKN2A gene and at a similar percentage (41%) of the tumors at the p14ARF gene and the CDKN2B gene. Most tumors with CDKN2A, p14ARF, and/or CDKN2B hypermethylation either lacked detectable transcripts from these genes or had lower mRNA levels than those determined for non-neoplastic brain tissue. There was a significant correlation between hypermethylation of these genes and the presence of allelic losses on chromosomal arms 1p and 19q. In addition, p14ARF hypermethylation was predominantly found in tumors without a demonstrated TP53 mutation. Taken together, our results indicate that hypermethylation of CDKN2A, p14ARF, and CDKN2B is an important epigenetic mechanism by which oligodendroglial tumors may escape from p53- and pRb-dependent growth control. PMID- 11764090 TI - Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. AB - Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16INK4a/p15INK4b and TP53/p14ARF/MDM2 pathways. In oligodendrogliomas, hypermethylation of RB1 (1 case) and p14ARF (6 cases) were the only detectable genetic changes (7/28, 25%). In anaplastic oligodendrogliomas, the RB1/CDK4/p16INK4a/p15INK4b signaling pathway regulating the G1 -->3 S transition of the cell cycle was altered in 13/20 (65%) cases, by either RBI alteration, CDK4 amplification, or p16IN4a/p15INK4b homozygous deletion or promoter hypermethylation. Further, 50% (10/20) of anaplastic oligodendrogliomas showed alterations in the TP53 pathway through promoter hypermethylation or homozygous deletion of the p14ARF gene and, less frequently, through TP53 mutation or MDM2 amplification. Of 13 anaplastic astrocytomas with an altered RB1 pathway, 9 (69%) also showed a dysregulated TP53 pathway. Thus, simultaneous disruption of the RB1/CDK4/p16INK4a/p15INK4b and the TP53/p14ARF/MDM2 pathways occurs in 45% (9/20) of anaplastic oligodendrogliomas, suggesting that these phenomena contribute to their malignant phenotype. PMID- 11764091 TI - Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis. AB - JNK and p38, two members of the MAP kinase family, are strongly induced by various stresses including oxidative stress and have been involved in regulation of apoptosis. As both kinases phosphorylate tau protein in vitro, we have investigated their immunohistochemical localization in a group of neurodegenerative diseases characterized by intracellular deposits of hyperphosphorylated tau. Cases included Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Gerstmann-Straussler Scheinker disease-Indiana kindred, and frontotemporal dementia with parkinsonism linked to chromosome 17. In all tissue samples, strong immunoreactivity for both MAP kinases was found in the same neuronal or glial cells that contained tau positive deposits. By double immunohistochemistry, JNK and p38 colocalized with tau in the inclusions. Analysis of apoptosis-related changes (DNA fragmentation, activated caspase-3) showed that the expression of JNK and p38 was unrelated to activation of an apoptotic cascade. Our data indicate that phospho-JNK and phospho-p38 are associated with hyperphosphorylated tau in a variety of abnormal tau inclusions, suggesting that these kinases may play a role in the development of degenerative diseases with tau pathology. PMID- 11764092 TI - White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. AB - Extracellular matrix (ECM) alterations in the central nervous system (CNS) of multiple sclerosis (MS) patients result from blood-brain barrier breakdown, release and activation of proteases, and synthesis of ECM components. To elucidate their potential pathophysiologic roles, we analyzed expression of major CNS ECM proteoglycans (PGs) in MS and control CNS tissues. In active MS plaque edges, 3 CNS lecticans (versican, aggrecan, and neurocan) and dermatan sulfate PG were increased in association with astrocytosis; in active plaque centers they were decreased in the ECM and accumulated in foamy macrophages, suggesting that these ECM PGs are injured and phagocytosed along with myelin. In inactive lesions they were diminished and in normal-appearing white matter they showed heretofore unappreciated abnormal heterogeneous aggregation. Phosphacan, an ECM PG abundant in both gray and white matter, was less markedly altered. Since in development the spaciotemporal expression of ECM PGs influences neurite outgrowth, cell migration, axon guidance, and myelination, these data suggest that 1) enhanced white matter lectican and dermatan sulfate PG expression in the pro-inflammatory milieu of expanding lesion edges contributes to their sharp boundaries and the failure of neuronal ingrowth; 2) decreases in plaque centers may preclude regeneration and repair; and 3) diffuse ECM PG damage relates to axon degeneration outside of overt lesions. Thus, ECM PG alterations are specific, temporally dynamic, and widespread in MS patients and may play critical roles in lesion pathogenesis and CNS dysfunction. PMID- 11764093 TI - Hypothalamic lesions in multiple sclerosis. AB - Demyelinating lesions of fiber bundles in and adjacent to the hypothalamus (i.e. the fornix. anterior commissure, internal capsule, and optic system) may be the basis for autonomic and endocrine alterations in multiple sclerosis (MS) patients. Therefore we investigated the presence and immunological activity of lesions in hypothalamic fiber bundles of 17 MS patients and 14 controls. In the MS group, 16 of 17 patients showed demyelinated lesions. The incidence of active lesions was high (60%) and outnumbered chronic inactive lesions in the internal capsule (p = 0.005). In 4 of 17 MS patients, axonal damage was observed and in 3 of 17 MS patients grey matter lesions were apparent. Duration of MS was inversely related to the active hypothalamic MS lesion score (r = -0.72, p = 0.001). Since comparison of hypothalamic lesions with MS lesions in other areas of the brain in the same patients (n = 7) showed a great similarity both as stage and appearance was concerned, this negative relation in all likelihood reflects the clinical consequences of high disease activity throughout the whole brain. In controls no demyelinating lesions were seen but in 11 control cases HLA expression was observed that was lower than that present in MS patients (p = 0.02). In the median eminence region that lacks a blood-brain barrier, all controls showed a strong HLA expression around the blood vessels. We conclude that systematic pathological investigation of the hypothalamus in MS patients reveals an unexpected high incidence of active lesions that may impact on hypothalamic functioning. PMID- 11764094 TI - Hyperphosphorylation of RNA polymerase II and reduced neuronal RNA levels precede neurofibrillary tangles in Alzheimer disease. AB - Affected neurons of Alzheimer disease (AD) brain are distinguished by the presence of the cell cycle cdc2 kinase and mitotic phosphoepitopes. A significant body of previous data has documented a decrease in neuronal RNA levels and nucleolar volume in AD brain. Here we present evidence that integrates these seemingly distinct findings and offers an explanation for the degenerative outcome of the disease. During mitosis cdc2 phosphorylates and inhibits the major transcriptional regulator RNA polymerase II (RNAP II). We therefore investigated cdc2 phosphorylation of RNAP II in AD brain. Using the H5 and H14 monoclonal antibodies specific for the cdc2-phosphorylated sites in RNAP II, we found that the polymerase is highly phosphorylated in AD. Moreover, RNAP II in AD translocates from its normally nuclear compartment to the cytoplasm of affected neurons, where it colocalizes with cdc2. These M phase-like changes in RNAP II correlate with decreased levels of poly-A RNA in affected neurons. Significantly, they precede tau phosphorylation and neurofibrillary tangle formation. Our data support the hypothesis that inappropriate activation of the cell cycle cdc2 kinase in differentiated neurons contributes to neuronal dysfunction and degeneration in part by inhibiting RNAP II and cellular processes dependent on transcription. PMID- 11764095 TI - Axonal dysfunction in adoptive transfer of experimental autoimmune neuritis with P2-specific CD4+ cells: the role of nerve ischemia. PMID- 11764096 TI - Gilbert syndrome associated with beta-thalassemia. AB - The authors investigated whether the considerable variability in serum bilirubin levels (STB) found in transfusion-dependent beta-thalassemia, beta-thal intermedia, and heterozygous beta-thalassemia individuals could be related to the coexistence of Gilbert syndrome (GS). The promoter region [A(TA)nTAA] of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) was analyzed in a total of 128 beta-thalassemia individuals (108 transfusion-dependent beta-thal patients, 20 very mild beta-thal intermedia) and in 33 beta-thal heterozygotes. The control group consisted of 70 healthy children with no history of anemia. The frequency of GS genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed between serum bilirubin levels (STB) and GS genotypes (TA)7/(TA)7 and (TA)6/(TA)7 and also between (TA)7/(TA)7 and (TA)6/(TA)6 for all groups examined. These results confirm that the (TA)7/(TA)7 GS genotype is one of the factors accounting for the hyperbilirubinemia observed in beta-thalassemia major, intermedia, and heterozygous individuals. PMID- 11764097 TI - Parotid and thyroid gland cancers in patients with ataxia-telangiectasia. AB - This study describes the clinicopathologic features of parotid and thyroid gland cancers in patients with ataxia-telangiectasia (AT). The medical records of 412 AT patients were reviewed to identify those patients who developed parotid or thyroid gland cancers. Presenting features, diagnoses, types of therapy, risk factors, and other primary cancers were analyzed. Five patients with parotid or thyroid gland cancers were identified. Three had parotid (2 mucoepidermoid and 1 acinic cell) and 2 had thyroid gland (1 papillary and 1 follicular) cancers. Four patients presented with head and neck masses and 1 had an occult papillary thyroid carcinoma. Four patients had more than one primary cancer. The only mode of therapy was surgery. The 2 patients with mucoepidermoid carcinoma had complete parotidectomies. One is alive without any evidence of disease 12 months after diagnosis and 1 died of refractory lymphoma without any evidence of mucoepidermoid carcinoma at autopsy. The patient with acinic cell carcinoma had a parotid biopsy only. The 2 patients with thyroid cancer were diagnosed at autopsy. The results indicate that patients with AT are at risk for developing multiple primary cancers including those of the parotid and thyroid gland, and should be evaluated for such primaries. PMID- 11764098 TI - Low serum carnitine concentrations in healthy children with iron deficiency anemia. AB - Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship. PMID- 11764099 TI - MDM2 and p53 in childhood acute lymphoblastic leukemia: higher expression in childhood leukemias with poor prognosis compared to long-term survivors. AB - In previous studies the authors have found increased expression of p53 and MDM2 proteins in leukemic cells in a majority of children eligible for bone marrow transplantation (BMT) due to relapse or prognostically unfavorable features. In this study the immunohistochemical expression of p53, MDM2, and p21Cip1 was investigated in bone marrow samples from the time of diagnosis in 30 children with acute lymphoblastic leukemia (ALL) surviving disease-free at least 5 years. This group was compared with 15 advanced ALL patients, admitted for BMT. In 7 of the BMT patients orginal diagnostic marrow samples were also available for analysis. Four out of 30 ALL patients in the relapse-free group expressed p53 in the original leukemic cell population, while 8/15 advanced ALL patients did before BMT (p = .014). Four out of 30 cases in the relapse-free group expressed MDM2, while 10/15 in the BMT group did (p = .0011). In retrospect, MDM2 overexpression at the time of diagnosis was also more common (p = .0098) in the BMT group as well as p53 overexpression (p = .054) compared to nonrelapsed patients. PMID- 11764100 TI - Treatment of alpha-fetoprotein secreting hepatoblastoma by response of serum alpha-fetoprotein levels: a new concept. AB - Hepatoblastoma, the commonest primary malignant liver tumor in infants and children, is usually associated with elevated serum alpha-fetoprotein (AFP) levels. The authors sought to determine if AFP levels can be used to modify treatment, thereby avoiding the wait for formal imaging studies and prolonged suboptimal treatment and limiting the use of effective but toxic chemotherapy. From April 1984 to December 1997, 8 children were diagnosed with AFP-secreting hepatoblastoma. Serum AFP levels were measured weekly. If AFP levels failed to improve, or increased on at least 2 successive examinations, the chemotherapy protocol was changed. When an excellent response was achieved, less toxic chemotherapy was substituted. Six patients (75%) were disease-free for at least 2 years, some with high-risk or metastatic disease. Two patients died. Six of the 7 nonmetastatic patients (86%) remain disease-free (only one had a resectable tumor). Chemotherapy changes resulted in reduced AFP levels in 7 patients. This study supports the use of AFP monitoring to modify treatment in hepatoblastoma responding to therapy with less toxic drugs and the use of nonstandard therapy when suboptimal responses are obtained. PMID- 11764101 TI - Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report. AB - Anti-HLA antibodies reportedly exist in 31% of pregnant women. However, few ocurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibody have been reported. In this study, maternal anti-HLA B60 and B61 antibodies were identified in patient serum at birth, but no anti-platelet antibodies were present. No maternal anti-HLA A2, A24, B51, or B52 antibodies were detected in patient serum. Platelet transfusion from the third donor was effective because these platelets expressed HLA A24 and B52 but not B60 or B61. Cross-matching tests between patient leukocytes or platelets and maternal serum were strongly positive, indicating that maternal anti-HLA antibodies were responsible for NAIT. This report is the first to demonstrate NAIT probably caused by maternal anti-HLA A24 and B52. PMID- 11764102 TI - Effect of short-course, high-dose steroid therapy in a child with myelodysplastic syndrome. AB - High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML). Here the beneficial effect of short-course HDMP therapy in a child with myelodysplastic syndrome (MDS) is reported. Oral methylprednisolone sodium succinate (Prednol-L) was administered at a single daily dose of 30 mg/kg for 5 days to a 4-year-old girl with refractory anemia with excess of blasts and hypocellular bone marrow before the initiation of chemotherapy. In addition to dramatic clinical improvement, the patient's white blood cell count increased from 2.3 x 10(9)/L to 5.0 x 10(9)/L, and peripheral blood blast cells disappeared 4 days after HDMP treatment. Repeated bone marrow aspirate 1 week after the initiation of HDMP disclosed increased cellularity with no blasts. Furthermore, short-course HDMP treatment stimulated the increase in the number of peripheral blood lymphocytes and CD3+, CD4+, CD8+, CD19+, CD34+, and NK cells. Results obtained with HDMP from the previous studies and the present case suggest that high-dose methylprednisolone is a promising agent in the treatment of AIDS and it is recommended as an initial treatment especially for MDS children with hypocellular bone marrow at presentation. PMID- 11764103 TI - Hemophagocytic syndrome: a rare life-threatening complication of visceral leishmaniasis in a young boy. AB - The authors report a case of hemophagocytic syndrome (HPS) associated with acute visceral leishmaniasis (VL). A 4-year-old boy was admitted with high fever, hepatosplenomegaly, and pancytopenia. Elevated serum ferritin and triglyceride, low fibrinogen levels, and bone-marrow (BM) histiocytic hyperplasia with prominent hemophagocytosis were consistent with a HPS. An initial diagnosis of kala-azar was refuted because of negativity of BM aspiration and serology for this parasite, and the diagnosis HPS was made. Three months after first admission, reevaluation of the BM aspiration revealed many amastigotes of Leishmania parasites. The serology of VL became positive, finally establishing the diagnosis of VL. Although specific therapy for VL was instituted, the patient died 4 weeks after the diagnosis. PMID- 11764104 TI - Lethal hydrops fetalis due to congenital dyserythropoietic anemia in a newborn: association of a new skeletal abnormality. AB - Congenital dyserythropoietic anemias (CDAs) are a group of hereditary refractory anemias characterized by ineffective erythropoiesis, typical morphological abnormalities of erythroblasts, a low or no reticulocyte response, hyperbilirubinemia, and splenomegaly. A massive hydropic newborn born with a very severe anemia (Hb 4.8 g/dL), diffuse edema, hepatosplenomegaly, ascites, pulmonary edema and respiratory distress, and shortness and hallux varus deformity of the great toe of the right foot was diagnosed to have congenital dyserythropoietic anemia on the basis of the hematological (macrocytosis, anisopoikilocytosis, fragmented red cells and erythroblastosis in the peripheral blood, and erythroid hyperplasia with erythroblastosis and erythroblasts with double nuclei and thin chromatin bridges connecting these nuclei in the bone marrow) and serological (negative acidified serum lysis test and no agglutination with anti-i antibodies) findings. In this article the seventh case of neonatal congenital dyserythropoietic anemia presenting with a very severe (lethal) form of hydrops fetalis and a new (hallux varus) deformity of the great toe of the right foot is presented. Congenital dyserythropoietic anemia should be considered in the differential diagnosis of hydrops fetalis presenting with a very severe anemia and a skeletal abnormality of the great toe. PMID- 11764105 TI - Enhanced vincristine neurotoxicity from drug interactions: case report and review of literature. AB - This study reports observed toxicity in a child with acute lymphocytic leukemia who had received vincristine (VCR) with nifedipine and itraconazole. A 5-year-old child with leukemia developed bilateral cranial nerve palsies, severe peripheral neuropathy involving upper and lower extremities, seizures, hypertension, heart failure, and syndrome of inappropriate antidiuretic hormone secretion after being treated with VCR, nifedipine, and itraconazole. Appropriate management of the above problems including discontinuation of VCR resulted in recovery from neurotoxic manifestations. Concurrent administration of VCR with nifedipine and itraconazole may enhance its neurotoxicity. PMID- 11764106 TI - Vaccination-associated immune thrombocytopenic purpura in five children. PMID- 11764107 TI - Compomer materials and secondary caries formation. AB - PURPOSE: To evaluate the role of compomers in secondary caries formation in vitro. MATERIALS AND METHODS: 36 human teeth with caries-free enamel (coronal) and root surfaces underwent a fluoride-free prophylaxis. Class V cavities were prepared in buccal and lingual coronal and root surfaces. The teeth were divided into two groups with 3 treatment subdivisions [12 teeth per restorative material (6 with coronal restorations and 6 with root surface restorations)]). The preparations were restored with: (1) filled composite (Filtek Z250 with Single Bond), (2) fluoride-releasing compomer [Hytac with Prompt L-Pop (fluoride releasing water-based adhesive)]; or (3) fluoride-releasing compomer [Dyract AP with Prime & Bond NT (fluoride-releasing acetone-based adhesive)]. 24 cavities (6 teeth with 2 cavities/tooth) were available with each treatment. The teeth were thermocycled (500 cycles at 5-50 degrees C) in synthetic saliva prior to artificial caries formation. After lesion formation, 5 longitudinal sections were taken from each specimen for polarized light evaluation. Mean surface lesion depths and wall lesion frequencies were determined. RESULTS: The Filtek Z250 group had significantly (P < 0.05, ANOVA, DMR) greater mean body of the lesion depths in coronal (205 microm) and root surfaces (221 microm) than either the Hytac (119 microm coronal and 161 microm root surfaces) or the Dyract AP (127 microm coronal and 149 microm root surfaces) groups. Likewise, wall lesion frequency was significantly higher (P < 0.05, ANOVA, DMR) for the Filtek Z250 group (41% coronal and 37% root surfaces) compared with either the Hytac (31% coronal and 25% root surfaces) or Dyract AP (26% coronal and 21% root surfaces) groups. No differences in outer body of the lesion depths or wall lesion frequencies were found between Hytac and Dyract AP for coronal and root surface restorations (P > 0.05, ANOVA, DMR). PMID- 11764108 TI - Microleakage of Class II resin-based composite restorations with flowable composite in the proximal box. AB - PURPOSE: To compare microleakage of Class II hybrid resin-based composite (RBC) restorations with and without low viscosity (flowable) RBC in the proximal box. MATERIALS AND METHODS: Conservative Class II cavity preparations were made in 50 extracted premolars randomly assigned to five groups (n = 10). OptiBond FL dentin bonding agent, and Prodigy hybrid RBC were used to restore all cavity preparations. Preparations in four of the five groups were restored with flowable RBC as the initial increment in the proximal box. The four flowable RBCs tested were: AEliteFlo, Revolution, UltraSeal XT and Flow-It. In the control group, the entire preparation was restored only with hybrid RBC. Specimens were stored in water at 37 degrees C for 24 hrs after restoration, thermocycled 1,000x, immersed in 2% basic fuchsin, sectioned and evaluated for microleakage. Microleakage was scored on a 0-4 scale. RESULTS: Non-parametric Kruskal-Wallis one-way ANOVA followed by Wilcoxon signed ranks test was used for statistical analysis. The use of any of the four flowable RBCs tested did not influence microleakage significantly (P > 0.05) in Class II RBC restorations. PMID- 11764109 TI - Influence of incorrect application of a water-based adhesive system on the marginal adaptation of Class V restorations. AB - PURPOSE: To determine the influence of incorrectly performed steps during the application of the water-based adhesive system OptiBond FL on the marginal adaptation of Class V composite restorations. MATERIALS AND METHODS: In 96 extracted human teeth Class V cavities were prepared. Half of the margin length was situated in dentin. The teeth were randomly divided into 12 groups. The cavities were filled with Prodigy resin-based composite in combination with OptiBond FL according to the manufacturer's instructions (Group O) and including several incorrect application steps: Group A: prolonged etching (60 s); Group B: no etching of dentin; Group C: excessive drying after etching; Group D: short rewetting after excessive drying; Group E: air drying and rewetting; Group F: blot drying; Group G: saliva contamination; Group H: application of primer and immediate drying; group I: application of only primer; group J: application of only adhesive; Group K: no light curing of the adhesive before the application of composite. After thermocycling, replicas were taken and the margins were quantitatively analyzed in the SEM. Statistical analysis of the results was performed using non-parametric procedures. RESULTS: With exception of the "rewetting groups" (D and E) and the group with saliva contamination (G), all other application procedures showed a significantly higher amount of marginal openings in dentin compared to the control group (O). Margin quality in enamel was only affected when the primer was not applied. PMID- 11764110 TI - Microleakage and retention of bonded amalgam restorations. AB - PURPOSE: To compare the microleakage and bond strength exhibited by two light cured, filled dentin bonding agents, a resin cement, and cavity varnish. MATERIALS AND METHODS: The four test groups of lining agents for amalgam restorations included (LF) Light-cured, Filled resin (Clearfil Liner Bond 2); (LCF) light- and chemical-cured, Filled resin (Clearfil Liner Bond + Protect Liner); (RC) Resin Cement (Panavia 21); and (V) Varnish (Copalite). For each group, 20 Class V cavity preparations were cut in human extracted molars. Tytin amalgam was condensed into the preparation. After storage for at least 24 hrs in distilled water at 37 degrees C, all restorations were subjected to 2500 thermal cycles (8 degrees C to 48 degrees C). After 1 wk, specimens were tested. For the leakage tests, teeth were immersed in 45Ca, sectioned, and radiographs of sections were evaluated and then evaluated by Ridit analysis. Retention samples were tested to failure in tension using an Instron machine and peak load (kg) was recorded. RESULTS: Compared to varnish, the two dentin bonding agents (LF and LCF) significantly decreased microleakage at the cementum margin but not at the enamel margin. The two dentin bonding agents also exhibited significantly greater retentive strength than either the resin cement or the varnish. PMID- 11764112 TI - Bonding to root canal: structural characteristics of the substrate. AB - PURPOSE: To evaluate in vitro the dentin morphology in root canals in terms of tubule orientation, density and increase in surface area after etching. MATERIALS AND METHODS: Thirty anterior teeth were divided in 3 groups at random: the samples of Group 1 were used to study tubular morphology in SEM. Groups 2 and 3 samples were etched with 32% phosphoric acid. The teeth in Group 2 were examined by SEM without further treatment. The samples in Group 3 were treated with a bonding system and fiber posts were luted into the canal. These teeth were then processed for evaluation of hybrid layer formation and resin tags in dentin tubules. The observations were made according to location in the root dentin, tubule density was estimated, and the increase in area available for bonding after etching was calculated. RESULTS: The observations revealed variability in tubule density and orientation within different areas of any one sample. Statistically significant differences in the density of tubules were found depending on location. The dentin surface area available for bonding increased by 202% after etching in the cervical third, 156% in the middle third, and 113% in the apical third of the root dentin. Group 3 samples showed that the thickness of the hybrid layer depended on the density of tubules. In the sectors with a low density of tubules, the hybrid layer was significantly thinner than in areas with a higher density of tubules. The increase in dentin surface area might be responsible for the enhanced bond strength after acid etching, but not all areas exhibited equal responses to etching. PMID- 11764111 TI - Bond strength of prosthodontic luting materials to titanium after localized cyclic loading. AB - PURPOSE: To establish an in vitro analysis system to evaluate the effect of cyclic loading on the bond strengths and durability of luting materials bonded to titanium. MATERIALS AND METHODS: Machine-milled titanium disks were finished with 600 grit silicon-carbide paper and pairs of disks were bonded together using the five different luting materials. A stainless steel stylus was vertically loaded at a center position (Model 1) or at the border (Model 2) of the specimens with a force of 75.6 N at 7500 cycles/hr. When the stylus contacted the specimen surface through the water slurry of poly(methyl methacrylate) beads, it rotated clockwise up to 15 degrees and counter-rotated. Shear bond strengths were determined 1 hr after bonding, after storage in water at room temperature for 24 hr, and after the loading for 100,000 cycles. RESULTS: The bond strengths of the unfilled adhesive resin and resin-based composite cement (RBC) were significantly higher than those of the glass-ionomer cements. Zinc phosphate cement demonstrated no bonding ability to titanium. After 100,000 cycles, peripheral loading in Model 2 significantly reduced the bond strength of the RBC and glass-ionomer cements, while Model 1 loading did not. The highest and the most durable bonds were obtained with the unfilled adhesive resin in both models. PMID- 11764113 TI - Effect of gingival fluid on marginal adaptation of Class II resin-based composite restorations. AB - PURPOSE: To evaluate in vitro the marginal quality of Class II composite restorations at the gingival enamel margins as affected by contamination of the cavities with gingival fluid (GF) during different steps of resin bonding procedures. MATERIALS AND METHODS: 70 Class II cavities were prepared in extracted human molars and restored with composite using a multi-component bonding system (OptiBond FL/Herculite XRV; OPTI) or a single-bottle adhesive (Syntac Sprint/Tetric Ceram; SYN). The cavities were contaminated with human GF: C1 after acid etching, C2 after application of the primer (OPTI) or light-curing of the primer-adhesive (SYN), and C3 after light-curing of the resin adhesive (OPTI). Uncontaminated cavities were used as the control (C0). The restored teeth were subjected to thermocycling (TC) and replicated for SEM analysis of marginal gap formation. Microleakage at the gingival margins was determined by dye penetration with basic fuchsin. STATISTICS: non-parametric tests (Kruskal-Wallis test, Mann-Whitney test with Bonferroni correction). RESULTS: In both bonding systems, contamination with GF after acid etching (C1) did not impair the marginal quality; the mean percentages of continuous margin/mean depths of dye penetration were: OPTI: C0: 88.5%/0.10 mm, C1: 95.6%/0.04 mm; SYN: C0: 90.9%/0.08 mm, C1: 97.0%/0.05 mm. Marginal adaptation was adversely affected when GF contamination was performed after PMID- 11764114 TI - Shear bond strength to moist and dry dentin of four dentin bonding systems. AB - PURPOSE: To compare the shear bond strength of four single-bottle adhesive systems (Prime & Bond NT, Single Bond, Gluma Comfort Bond, Gluma Comfort Bond + Desensitizer) bonded to moist and dry dentin. MATERIALS AND METHODS: A column of resin-based composite was bonded to human dentin using the dentin bonding systems following manufacturers' directions (n= 12). For half the specimens, the dentin was dried completely after acid etching (air dried for 10 s). For the remaining specimens, the dentin was left moist (glistening appearance with no puddles) after acid etching. All specimens were thermocycled for 1,000 cycles at 6-60 degrees C, placed in a fixture on an MTS machine and loaded in shear until failure. RESULTS: Statistical analysis revealed that dentin condition (moist or dry) was significant for Prime & Bond NT, Single Bond, and Gluma Comfort Bond. Bonding to moist dentin produced higher bond strengths than bonding to dry dentin. For Gluma Comfort Bond + Desensitizer, no statistical difference was found between bonding to moist vs. dry dentin. Over all, Single Bond and Gluma Comfort Bond bonded to moist dentin produced significantly higher bond strengths than all other groups. PMID- 11764115 TI - Video rate confocal microscopic imaging of dentin/adhesive interfacial failure under load. AB - PURPOSE: To obtain information on interfacial failure by recording video rate images of the interface as it failed, while simultaneously recording the load applied. MATERIALS AND METHODS: Fluorescent labeled adhesives were used to retain resin-based composite bobbins on the flat exposed dentin surface of teeth included in epoxy resin blocks. The teeth were secured in a miniature straining stage while the bobbins were loaded in shear mode and the interface viewed with a tandem scanning confocal microscope. Images of the interface during failure were recorded with the aid of computer image processing and storage. The dynamic failure pattern, site of failure (after repositioning the fractured bobbin under the microscope) and shear bond stress were analyzed for four dentin adhesives [OptiBond (OB), Scotchbond Multi-Purpose Plus (SBMP+), Clearfil Liner Bond 2 (CFLB2) and ESPE Bonding System (EBS)]. Control specimens without fluorescent dyes were also studied. Four dynamic patterns of failure were observed: snap, slip/stick, peel and shock wave were seen respectively with OB, SBMP+, CFLB2 and EBS adhesive. The shear bond strengths were ranked EBS*>OB>SBMP+>CFLB2* (*statistically different at alpha=0.05). No significant difference was found between specimens with and without fluorescent dye. PMID- 11764117 TI - Applied research still needed on infection control procedures. PMID- 11764116 TI - Influence of Erbium:YAG laser energies on the microleakage of Class V resin-based composite restorations. AB - PURPOSE: To evaluate the influence of three Erbium:YAG laser energies on the microleakage of Class V resin-based composite restorations. MATERIALS AND METHODS: 60 extracted human premolar teeth stored in 0.12% thymol solution were randomly allocated to three groups. Buccal and lingual box-shaped Class V cavities were prepared on each tooth. One cavity served as the control and was cut using a conventional diamond bur in a high-speed handpiece. The test cavity was prepared using a pulse repetition rate of 5 Hz with 1 of 3 pulse energies; 200 mJ, 240 mJ, and 300 mJ with a 100 mJ dentin finish. The cavities were restored with Scotchbond Multi-Purpose and Z100 and were finished immediately before being stored for 3 months in thymol solution at 37 degrees C. Following thermocycling between 5 degrees C and 55 degrees C for 240 cycles and a further 12 hrs storage, the teeth were immersed in a 2% aqueous solution of methylene blue for 24 hrs. They were then sectioned through the mid-point of the restorations in a bucco-lingual plane and dye penetration was scored as 0 (none) to 4 (to the axial wall) for the enamel and dentin margins of both sections. The worst score for each margin was used for statistical analysis using the Kruskal Wallis and Mann-Whitney U tests at P < 0.05. RESULTS: When the lased groups were compared, optimum sealing was achieved with energies of at least 240 mJ at the enamel margin and with energies no higher than 200 mJ to finish the dentin margin. However, while all the pulse energies compared favorably to the control group in enamel, a similar result was found only using the 300 mJ, with 100 mJ, finish at the dentin margins. PMID- 11764118 TI - Mustache grooming associated with angular cheilitis. PMID- 11764119 TI - Rapid general dental erosion by gas-chlorinated swimming pool water. Review of the literature and case report. AB - Several reports indicate an increased prevalence of dental erosion among intensive swimmers due to low pH gas-chlorinated pool water. Contrary to other extrinsic factors which induce erosion located on the facial aspect, low pH pool water results in general dental erosion. Additionally, a case report is presented which describes the very rapid occurrence of excessive general dental erosion of a competitive swimmer due to gas-chlorinated pool water within 27 days. The observation of several authors as well as this case underscore the significance of a regular pH monitoring of chlorinated swimming pool water. The high incidence indicates that dental erosion due to frequent swimming is of considerable diagnostic and therapeutic significance. Furthermore, it is recommended to fluoridate the teeth of intensive swimmers regularly to prevent dental erosion. PMID- 11764121 TI - Influence of acidulated phosphate fluoride agents on surface characteristics of composite restorative materials. AB - PURPOSE: To evaluate the surface changes of resin-based composites (RBC) when they were exposed to acidulated phosphate fluoride (APF) agents. MATERIALS AND METHODS: One microfilled (Silux Plus) and four hybrid (Clearfil AP-X, Lite-Fil IIA, Palfique Estelite, Progress) RBCs were separately treated with two APF agents (Fluorident Gel, Floden A). Changes in surface roughness were determined with a surface analyzer, and relief patterns were observed using a scanning electron microscope. RESULTS: Although the surfaces of hybrid RBC materials containing macro-inorganic filler particles were generally found to be rougher than that of the microfilled composite regardless of APF treatment, macro inorganic fillers in two of the hybrid composites demonstrated noticeable etched patterns generated by an APF solution. PMID- 11764120 TI - Clinical evaluation of a polyacid-modified resin used as a fissure sealant: 48 month results. AB - PURPOSE: To evaluate the incidence of occlusal caries and the rates of retention using Variglass VLC (polyacid-modified resin) as an occlusal sealant. MATERIALS AND METHODS: The sample consisted of 185 school children (6-8 yr-old), with sound unsealed permanent first molars. Sealants were applied on the upper and lower first molars from a randomly chosen hemiarch (N=370 teeth). The follow-up was conducted at 6, 12 and 48 months examining 343 (93%), 290 (78%) and 187 (51%) teeth, respectively. RESULTS: After 48 months, total retention of the material was noted in only 5% of the teeth. The presence of sealant in 2/3 and 1/3 of the pit extension was verified in 8% and 14% of the teeth, respectively, while 73% of the sealed teeth had no sealant present on the occlusal surface. Caries incidence, measured by the presence of dental caries and restorations, was 16% representing an annual increase of 4%. PMID- 11764122 TI - Fluoride release from light-curing restorative materials. AB - PURPOSE: To measure the in vitro fluoride release from three polyacid-modified resin-based composites (Dyract AP, Compoglass F, F2000) and one resin-modified glass-ionomer cement (Vitremer VLC) for 28 days in two different buffer solutions. MATERIAL AND METHODS: 30 cylindrical specimens of each material were prepared. Subsequently, 15 samples of each material were stored in neutral (pH 6.8) and acidic (pH 4.0) buffer solution (5 mL), respectively. After 4, 8, 12 hrs and 1, 2, 4, 8, 14 days, respectively, the samples were transferred into new solutions. The fluoride content was determined with a fluoride sensitive electrode. Data were analyzed with ANOVA, followed by closed-test-procedure based on Kruskal-Wallis. RESULTS: Compared to the neutral solution, all materials showed a significantly higher release of fluoride in acidic environment within the 28-day period (P < 0.001, ANOVA). In acidic buffer solution Vitremer VLC and Compoglass F showed a significantly higher fluoride release than F2000 and Dyract AP (P < 0.001, closed-test-procedure). In neutral solution Dyract AP showed the significantly lowest release (P < 0.001, closed-test-procedure). Fluoride release from the materials tested is higher in an acidic environment than in a neutral environment. PMID- 11764123 TI - Patient preference between visible light-cured and heat-cured acrylic splints. AB - PURPOSE: To compare the advantages/disadvantages concerning patient subjective preferences of splints made with heat-cured acrylic (Splint Resin Polymer) or visible light-cured material. MATERIAL AND METHODS: A questionnaire was developed assessing: comfort, stability, fit, taste, occlusal contacts, lip seal, smoothness, hygiene, color stability, stain resistance, salivation level, gingival irritation, bulkiness and odor. 10 patients already treatment planned to receive splints, were chosen at random from the dental school. Splints made from the two types of materials were delivered to each patient to be used for 3 wks. The material to initially be used was chosen at random and the questionnaire was answered after each 3-wk period. RESULTS: The MacNemar's Chi-square test revealed that there was no statistical difference in patient preference between the two splint materials. PMID- 11764124 TI - Dentin bond strength of packable composites using one-bottle adhesives. AB - PURPOSE: To evaluate the shear bond strength to dentin of packable composites using their respective one-bottle adhesives. MATERIALS AND METHODS: Human, noncarious extracted permanent molars stored in distilled water were used. Flat buccal and lingual dentin surfaces were ground wet on 600-grit silicon carbide paper. The teeth were then distributed at random into four groups of 8 teeth (16 surfaces) each: Group 1: Gluma Comfort Bond/Solitaire II; Group 2: Bond 1/Alert; Group 3: Prime & Bond NT/Surefil; Group 4: OptiBond Solo/Prodigy Condensable. Group 5: Single Bond/Z250 (control) Cylindrical samples of the materials were prepared in plastic molds and bonded to the dentin surface according to the manufacturers' instructions. All samples were placed in distilled water for 24 hrs, thermocycled for 500 cycles in distilled water at 6 degrees C and 60 degrees C and sheared with a universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: In MPa: Group 1: 24.39 +/- 3.54; Group 2: 28.96 +/- 4.62; Group 3: 30.77 +/- 4.71; Group 4: 30.82 +/- 3.29; Group 5: 24.93 +/- 5.14. ANOVA revealed that Groups 1 and 2 were statistically significantly different from the other groups; there was no statistically significant difference between Groups 2, 3 and 4. PMID- 11764125 TI - Microleakage of resin-based composite restorations with ceramic inserts. AB - PURPOSE: To evaluate dye penetration of proximal vertical slot resin-based composite (RBC) restorations as a function of cavity size and restorative material employed (RBC, ceramic inserts with low-viscosity resin, and RBC with low-viscosity resin liner). Microleakage was measured using rank scoring and linear measurement of dye penetration and ANOVA and non-parametric tests were used to evaluate the statistical significance of the results. MATERIALS AND METHODS: Ninety erupted crack- and caries-free mandibular third molars, extracted for orthodontic reasons, were used. Proximal vertical slots were prepared on the mesial surfaces of the teeth using diamond instruments at high speed under distilled water coolant. Teeth were placed randomly into nine groups. Three sizes of diamond burs of an ultrasonic cavity preparation system were used under low energy in order to standardize cavity size and shape, each tip size being used in 30 different teeth. The gingival margins were prepared 1 mm above the cemento enamel junction. Specimens were etched, prepared with bonding agent, restored using three different materials, and immersed in a 50% AgNO3 solution for 8 hrs and sectioned to evaluate the dye penetration. RESULTS: Statistical analysis revealed no statistically significant differences among the nine groups. PMID- 11764126 TI - Enamel wear of modified porcelains. AB - PURPOSE: To evaluate the wear of three different modified ceramics along with a conventional porcelain and the wear of opposing enamel at initial wear cycle on a two-body and a three-body wear simulation. MATERIALS AND METHODS: Modified ceramics used in this study included a low fusing/low crystal porcelain (Finesse), a high fusing/low crystal porcelain (Softspar), and a heat-pressable ceramic (IPS Empress). A conventional porcelain (Ceramco II) was used as the control material. Hemispherical shaped ceramic styli (1/8 inch in diameter) made of respective materials were fabricated according to the manufacturers' directions. Proximal surfaces of non-carious human molars were ground flat within the enamel with a silicon carbide paper to 600 grit with copious irrigation. They were perpendicularly opposed to each other with or without intermediate material as a food bolus and subjected to in vitro wear test by a UAB wear simulator. A 75.6 N load was applied vertically onto the surface at 1.2 Hz. The surface was duplicated after respective wear cycles. Seven specimens were tested for each group of both simulations. RESULTS: The enamel wear loss when opposing the modified ceramics was less than the Ceramco II control which exhibited the greatest values. The IPS Empress material showed the least amount of wear among them. Statistically significant differences were seen between the IPS Empress and the Ceramco II for every cycle interval evaluated (ANOVA, P < 0.05). Although the enamel wear loss when opposing the IPS Empress was significantly less (ANOVA, P < 0.05) than the others until 20,000 wear cycles, no significant differences were found among the modified ceramics at the end of 50,000 wear cycles. The concentric wear patterns were already prominent at 5,000 wear cycles on two-body wear, however, the wear facet of the three-body wear was smaller (the wear depth of 0-5 microm) than the two-body wear test, as it was quite similar to the one of the two-body wear test at 100 wear cycles. On the other hand, although no statistically significant differences were found among the three modified ceramics and between the conventional porcelain and the modified ceramics at every wear cycle, the high values of the Finesse since 10,000 wear cycles were probably due to the mechanical properties of this porcelain. Moreover, on the surface of the ceramic styli at the end of 50,000 wear cycles, the glaze layer on the contact area had not yet worn off. PMID- 11764127 TI - Comparative microtensile bond strength and SEM analysis of bonding to wet and dry dentin. AB - PURPOSE: To compare bond strengths of resins to acid-etched wet vs. dry dentin. MATERIALS AND METHODS: Human third molars were bonded with One-Step (OS), Single Bond (SB) or Clearfil PhotoBond (PB) under control moist or air-dried (5 s air blast) conditions. Tensile bond strengths were tested using the microtensile bond testing method. Scanning electron microscopy was done to evaluate the quality and thickness of the hybrid layers following polishing and acid plus NaOCl-challenge. RESULTS: The tensile bond strengths of OS, SB and PB were significantly (P < 0.01) lower (8-19 MPa) to air-dried dentin than to moist dentin (39-50 MPa). No hybrid layers were seen in the air-dried specimens bonded with OS or SB, while relatively thin hybrid layers were produced by PB. In contrast, moist dentin produced high bond strengths with all bonding systems and created thicker, acid/NaOCl-resistant hybrid layers. These results support the predictions of a previously published morphologic model and offer a morphologic explanation for the differences in bond strengths between wet vs. dry bonds. PMID- 11764128 TI - Role of hybridization on marginal leakage and bond strength. AB - PURPOSE: To evaluate whether the hybrid layer significantly contributes to the seal of adhesive Class V restorations placed in vivo and to the bond strength obtained in vitro. MATERIALS AND METHODS: 20 periodontally severely compromised anterior teeth were selected for the leakage study. In each tooth, one round 3 mm wide V-shaped cavity with a maximum depth of 2 mm was prepared on the labial surface crossing the cementum-enamel junction. The sample teeth were randomly divided into two groups of ten samples each: in Group 1, Scotchbond Multi-Purpose Plus was applied in combination with Z-100 following the manufacturer's instructions. In Group 2 the bonding procedure was the same as in Group 1, except that after the phosphoric acid treatment, the cavities were treated with 5% NaOCl for 2 min. Following a period of clinical service of 60-90 days, the teeth were extracted and processed for the leakage test. RESULTS: At the enamel site, 30% of the samples of Group 1 and 70% of the samples of Group 2 showed dye penetration. At the dentin site, 50% of the samples of Group 1 showed leakage, while all the samples of Group 2 were severely infiltrated. Statistically significant differences between the groups both for the enamel sites (P < 0.05) and for dentin-cementum sites (P < 0.001) were found. Bond strength tests were performed on 2 mm thick dentin slides of tapered Class I cavities (n = 10 in each group). The mean bond strength value obtained from cavities treated without NaOCl was 15.23 (+/-1.40) MPa and with NaOCl treatment 20.52 (+/-1.70) MPa. Statistical analysis showed significant differences (P < 0.05) between the two groups. No hybrid layer was detected on the NaOCl-treated samples by scanning electron microscopy. PMID- 11764129 TI - Effect of different single-bottle dentin adhesives on vascular responses in rat carotid artery. AB - PURPOSE: To investigate the effect of one-bottle dentin bonding systems on pulpal hemorrhage control in direct pulp exposures through contraction of pulp blood vessels using the rat carotid artery model. MATERIALS AND METHODS: Four dentin bonding agents (Prime & Bond 2.1, Prime & Bond NT, Syntac Single Component and Single Bond) were used. The efficacy of bonding agents were compared to that of epinephrine (control) in the viewpoint of the concentration applied and the contraction forces induced on the smooth muscle were recorded using a force displacement transducer. RESULTS: Three of the test materials produced epinephrine-like contractions on the rat carotid artery (smooth muscle) while no reading could be achieved with Single Bond. A ranking between the bonding agents for contraction forces was obtained as follows: Prime & Bond NT > Prime & Bond 2.1 > Syntac Single Component (P < 0.05). PMID- 11764130 TI - Infection control products and equipment must be used correctly. PMID- 11764131 TI - Sialolithiasis involving the maxillary alveolar mucosa. PMID- 11764132 TI - The observation care unit as part of the emergency department revisited. PMID- 11764133 TI - A short-stay observation unit improves care in the paediatric emergency care setting. AB - The aim of this study was to evaluate the influence of a short-stay observation unit (SSOU) on the hospitalization rate, the authors have analysed the activity of a SSOU opened in 1992 in a paediatric emergency department (PED) and the number of children hospitalized between 1987 and 1996. Among 2321 patients admitted to the SSOU in 1996, 644 medical patients have been analysed, showing a young population (55% under 3 years old), living in the town or surroundings (70%) and usually have not been referred by a general practitioner (64%). Twenty per cent were admitted for accurate diagnosis (group A), 49% for treatment and observation of a recognized acute pathology before decision of discharge (group B), and 31% waiting for a bed in a paediatric ward (group C). Sixty-eight per cent of children spent less than 6 hours in the SSOU, and 79% of those from groups A and B were thereafter discharged home. Between 1987 and 1991, the number of children hospitalized increased 5% per year on average. After the opening of the SSOU in 1992, this increase has been stopped although the number of medical referrals to PED was still going up. The SSOU in a PED can provide comprehensive care to young children requiring short-term treatment or observation, and is effective in limiting unappropriate hospitalizations. PMID- 11764134 TI - Attendance of patients with minor head injury in an emergency department observation ward. AB - A retrospective study was undertaken to compare the management of head injured patients in a short stay ward (SSW) with their management in other departments in the same hospital, where there is no neurosurgery department. Head injured patients were admitted to the general surgery department until November 1998, when the SSW was inaugurated. The following data were collected for all head injured patients admitted between 1997 and 1999: age, gender, diagnosis, outcome categories and length of stay. A total of 225, 238 and 340 head injured patients were admitted in 1997, 1998 and 1999 respectively. Patients in the neurology department were older (60 +/- 23 years) than in the SSW (41 +/- 23 years) and general surgery department (42 +/- 20 years). Patient diagnosis was similar in the SSW, paediatrics and general surgery departments but patients admitted to the neurology department had more skull fractures and intracranial injuries. The length of stay was longer in general surgery (3.5 +/- 3.9 days) and neurology departments (9.6 +/- 19.1 days) than in the SSW (1.4 +/- 0.8 days) and paediatrics department (1.5 +/- 1.5 days). Thirteen patients in the SSW required admission to another department in the hospital and only one was transferred to the neurosurgery department in another hospital. The results support the view that SSWs are suitable in the management of head injured patients. PMID- 11764135 TI - Helium-oxygen breathing in the early emergency care of acute severe asthma: a randomized pilot study. AB - The aim of this study was to establish whether a clinical trial, comparing helium oxygen (HeO2) breathing to standard therapy, would be feasible during the out-of hospital care of adult patients with severe asthma. Although the primary outcome in a definitive trial will be a decrease in morbidity, the present study primarily examined: (1) if the strategy could be successfully implemented in emergency ambulatory units; (2) if the research staff could enroll enough patients, given the resources. Nine patients were included in the conventional treatment group, and seven patients in the HeO2 group. Patients randomized to the HeO2 group breathed the mixture for a 12-hour period. Clinical and biological parameters improved for all patients. There was no trend towards a HeO2 benefit, whether during the initial out-of-hospital nor the ICU care. No patient was intubated within the study period. HeO2 breathing was considered to be simple to initiate, and no side effects were reported. In conclusion, while HeO2 breathing is easy to apply, even in the out-of-hospital setting, the few enrolled patients did not appear to benefit from this treatment. Regarding our low inclusion rate and the lack of positive effect trend, we believe that a large definitive trial will be difficult to initiate in such an emergency care setting. PMID- 11764136 TI - Patients admitted to the emergency department with acute chest pain--is there a difference between patients in an urban and a rural area? AB - The aim of this study was to compare the characteristics and outcome for patients coming to the emergency department with acute chest pain in a city university hospital, representing an urban area, and a county hospital, representing a rural area. This was a retrospective survey of all chest pain patients at Sahlgrenska University Hospital, Goteborg, covering an area with 706 inhabitants/km2, and at Uddevalla County Hospital, Uddevalla, covering an area with 34 inhabitants/km2, over a period of 6 months. In all 2,297 patients were registered at Sahlgrenska University Hospital and 1062 at Uddevalla Hospital (per 100,000 inhabitants and year 1,502 and 1,342 patients, respectively). The patients in the urban area were more frequently sent home from the emergency department than in the rural area (30% versus 23%; p < 0.0001). Patients in the urban area had a lower prevalence of previous cardiovascular diseases. An obvious acute myocardial infarction (AMI) or a strong suspicion of AMI at initial evaluation was less frequent in the urban area whereas no suspicion of AMI was twice as common (46% versus 24%; p < 0.0001). Furthermore, there was a difference in the use of medications; various cardiovascular drugs were more frequently used in the rural area. Despite these differences at baseline the 30-day mortality was similar (3.5% in the urban area and 3.6% in the rural area; NS), as well as the 2-year mortality (14.0% and 12.7%, respectively; NS). It is concluded that the number of patients admitted to the emergency department with acute chest pain/100,000 was slightly higher in the urban than in the rural area. Patients in the urban area differed from those in the rural area having a lower prevalence of previous cardiovascular diseases, a lower initial suspicion of AMI, they were less frequently hospitalized and less frequently prescribed various cardiovascular drugs. Mortality did not differ between the two cohorts. PMID- 11764137 TI - Magnesium efficacy in magnesium deficient and nondeficient patients with rapid ventricular response atrial fibrillation. AB - We assessed the effect of magnesium sulphate (MgSO4) on lowering the rate in ventricular atrial fibrillation (AF), and evaluated the effect of this therapy in magnesium (Mg) deficient and nondeficient patients. This experimental clinical study was performed on 34 patients with rapid AF (ventricular rate [VR] > 120/minute) presenting to the emergency department of a tertiary care university hospital. Patients with systolic blood pressure < or = 100 mmHg, Hb level < or = 11.8, saO2 of < or = 96%, BUN > or = 40 or creatine > or = 1.8 were excluded (n = 15). Nineteen patients were given an initial 2 g MgSO4 bolus i.v. and a 1 g/hour continuous infusion over 6 hours. To evaluate the presence of Mg deficiency, urine was collected from the onset of treatment and continued for the next 24 hours, and the excretion rate of administered Mg was calculated. Ventricular rates were obtained at baseline, after MgSO4 bolus, and every 15 minutes for the first hour. The decrease in the VR was statistically significant at 15, 30 and 60 minutes after Mg therapy (p = 0.0025, p < 0.001, p > 0.001). There was no difference in the response to Mg therapy between Mg deficient and nondeficient patients at 15, 30 or 60 minutes after therapy (p = 0.41, p = 0.28, p = 0.08). It is concluded that i.v. MgSO4 has a statistically significant but clinically limited effect on VR and this effect did not differ between patients with and without Mg deficiency. PMID- 11764138 TI - Transient global amnesia or subarachnoid haemorrhage? Clinical and laboratory findings in a particular type of acute global amnesia. AB - Acute global amnesia may be due to several causes, such as transient global amnesia (TGA), acute drug-related confusional state, toxic substances, metabolic abnormalities, infective diseases, cerebral tumours, cerebrovascular accidents, subarachnoid haemorrhage and epilepsy. In particular both TGA and subarachnoid haemorrhage may be precipitated by sexual activity; by contrast the two diseases are quite different in prognosis and treatment. Ten subjects were admitted in the period 1997-99 to our emergency department for acute global amnesia related to sexual activity. They represented 18% of total acute global amnesias observed in the same period. All patients were males, aged between 41 and 64 years. TGA was found in nine cases, while one patient had subarachnoid haemorrhage, due to rupture of an aneurysm of the right middle cerebral artery. The patient with subarachnoid haemorrhage showed neurologic defects (second-degree nystagmus and retropulsion), while no major neurologic abnormalities were found in TGA. Likewise computerized tomography (CT) scan was positive only in the case of subarachnoid haemorrhage. Patients and relatives in most cases left out sexual activity as a trigger factor. This experience indicates that acute global amnesia related to sexual activity is mostly due to TGA. Major neurologic signs are suggestive of subarachnoid haemorrhage and an immediate CT scan is recommended. Targeted questions are needed to identify the cause of the event. PMID- 11764139 TI - An unconscious man with transient exposure of an accessory pathway. PMID- 11764140 TI - Haematemesis resulting from ischaemic strangulating intestinal obstruction. AB - Although bleeding into the intestinal lumen may occur in strangulating intestinal obstruction, haematemesis is infrequently encountered. We report on a patient who presented with haematemesis and who had, in addition, clinical and radiological features of small bowel obstruction. Upper gastrointestinal endoscopy did not locate the source of bleeding. At laparotomy, which was performed because of clinical deterioration, gangrenous strangulated small bowel secondary to adhesive obstruction was found. In a patient with non-resolving intestinal obstruction, a deterioration in the condition is a clear indication for exploration. Haematemesis occurring concurrently may be a marker of intestinal strangulation, adds strength to the indication and highlights the urgency of the need for exploration. PMID- 11764141 TI - Delayed upper airway obstruction following a retropharyngeal haematoma after minor head trauma. AB - The development of a retropharyngeal haematoma may occur rarely after major head, face or cervical spine injuries, and it is even less frequent following minor trauma. As these patients are commonly not intubated, a life-threatening upper airway obstruction may occur. We report the case of a man who experienced a late retropharyngeal haematoma with delayed, progressive upper airway obstruction after a minor frontal wound. After an emergency intubation a nuclear magnetic resonance highlighted the magnitude of the bleeding into the retropharynx accounting for the slow onset of the symptoms. Predisposing factors such as antithrombotic therapies and vascular lesions may enhance the risk of occurrence even after minor trauma. Hypotheses on how to identify this potentially fatal complication earlier are reported. PMID- 11764142 TI - Spontaneous haemoperitoneum from surreptitious ingestion of a rodenticide. AB - Superwarfarins have progressively replaced warfarin as rodenticides as they are more potent and have a longer anticoagulant activity. Human exposure may be complicated by spontaneous haemorrhage in various sites. We report the case of a 51-year-old woman who was admitted with spontaneous haemoperitoneum and intramural haematoma along the small intestine. After the evidence of a deficit of vitamin K1-dependent clotting factors (II, VII, IX, X), the patient admitted that she was chronically ingesting difenacoum. She was successfully treated with fresh frozen plasma and vitamin K1. Follow-up was not accepted. PMID- 11764143 TI - A missed injury of the talus in a basketball player. PMID- 11764144 TI - Fulminant purpuric rash. AB - We report on a fatal case of purpura fulminans caused by severe meningococcaemia. Despite early and aggressive treatment with the use of a specific algorithm and the maintenance of a stable haemodynamic status in the first hour since admission, purpura fulminans developed impressively over a few minutes. Necropsy showed microvascular thrombosis in the dermis but not in visceral organs, suggesting the diagnosis of meningococcal septic shock with purpura fulminans limited to the skin. Acquired deficiency of protein C, which exerts anticoagulant and antiinflammatory functions, is the central mechanism ultimately responsible for purpura fulminans. The disorder predicts a poor outcome of meningococcaemia and early and aggressive resuscitation is recommended in the emergency department with antibiotics, volume expansion, inotropic drugs, and protein C replacement. An attitude of scepticism is appropriate in the management of these patients even when early resuscitation is successful and haemodynamic parameters remain stable. PMID- 11764145 TI - A rapid screening method for acid-volatile sulfide in sediments. AB - A new, direct method for the determination of acid-volatile sulfide (AVS) in sediments is presented. The method utilizes the direct reaction of Clines reagent with small amounts of sediment followed by colorimetric determination of AVS and offers fast analysis times without the need for specialized glassware or equipment. A comparison between AVS measured by this method and that measured by a purge-and-trap AVS method shows a linear relationship (r = 0.986, p < 0.001), although the method underestimates the AVS concentration measured by the purge and-trap method. Sample throughput by the direct AVS method is more than 10 times that of purge-and-trap methods. The applicability of the direct AVS method to the rapid screening of AVS concentrations in sediments and for evaluating sediment quality with respect to metal contamination is demonstrated. PMID- 11764146 TI - Acute toxicity of heavy metals to acetate-utilizing mixed cultures of sulfate reducing bacteria: EC100 and EC50. AB - Acid mine drainage from abandoned mines and acid mine pit lakes is an important environmental concern and usually contains appreciable concentrations of heavy metals. Because sulfate-reducing bacteria (SRB) are involved in the treatment of acid mine drainage, knowledge of acute metal toxicity levels for SRB is essential for the proper functioning of the treatment system for acid mine drainage. Quantification of heavy metal toxicity to mixed cultures of SRB is complicated by the confounding effects of metal hydroxide and sulfide precipitation, biosorption, and complexation with the constituents of the reaction matrix. The objective of this paper was to demonstrate that measurements of dissolved metal concentrations could be used to determine the toxicity parameters for mixed cultures of sulfate-reducing bacteria. The effective concentration, 100% (EC100), the lowest initial dissolved metal concentrations at which no sulfate reduction is observed, and the effective concentration, 50% (EC50), the initial dissolved metal concentrations resulting in a 50% decrease in sulfate reduction, for copper and zinc were determined in the present study by means of nondestructive, rapid physical and chemical analytical techniques. The reaction medium used in the experiments was designed specifically (in terms of pH and chemical composition) to provide the nutrients necessary for the sulfidogenic activity of the SRB and to preclude chemical precipitation of the metals under investigation. The toxicity-mitigating effects of biosorption of dissolved metals were also quantified. Anaerobic Hungate tubes were set up (at least in triplicate) and monitored for sulfate-reduction activity. The onset of SRB activity was detected by the blackening of the reaction mixture because of formation of insoluble ferrous sulfide. The EC100 values were found to be 12 mg/L for copper and 20 mg/L for zinc. The dissolved metal concentration measurements were effective as the indicators of the effect of the heavy metals at concentrations below EC100. The 7 d EC50 values obtained from the difference between the dissolved metal concentrations for the control tubes (tubes not containing copper or zinc) and tubes containing metals were found to be 10.5 mg/L for copper and 16.5 mg/L for zinc. Measurements of the turbidity and pH, bacterial population estimations by means of a most-probable number technique, and metal recovery in the sulfide precipitate were found to have only a limited applicability in these determinations. PMID- 11764147 TI - Biotransformation of n-hexadecane by cell suspension cultures of Cinchona robusta and Dioscorea composita. AB - This manuscript evaluates the phytotoxicity and biotransformation of n-hexadecane as well as peroxidase activity and cytochrome P450 concentration in microsomes for cell suspension cultures of Cinchona robusta and Dioscorea composita. Phytotoxicity was evaluated based on viability and growth. Cell cultures were exposed to a 2 and 4% (v/v) dose of n-hexadecane. The biotransformation of n hexadecane was determined based on labeled recovery in polar, nonpolar, and cell residue fractions after cell culture extraction during exponential cell growth phase and stationary phase. Differences were observed in accumulation of label during cell growth phase and stationary phase for the cells of the two plants. Differences also were observed between phases for label in polar and nonpolar fractions. Thin-layer chromatography determined labeled intermediates and some were identified. The activity of peroxidase and concentration of cytochrome P450 was lower in C. robusta than in controls and greater in D. composita than in controls. In vitro biotransformation was not successful. PMID- 11764148 TI - Stable carbon and nitrogen isotope analysis of TNT: two-dimensional source identification. AB - Data from a combination of laboratory and fieldwork is presented to initiate testing of stable carbon and nitrogen isotope ratios to trace sources of TNT in contaminated soil and groundwater. Evaluation of these extraction methods resulted in 99.9 and 99.8% recovery of TNT with Soxhlet and solid-phase extraction (SPE), respectively. As a result of the high extraction efficiency, isotope fractionation did not occur, thus providing an accurate stable isotope value on TNT from laboratory and field samples. Subsequent experiments evaluated the stability of isotope signatures through incubations lasting up to four weeks with a 70% decline in the TNT concentration. During these experiments, no significant variation in stable carbon and nitrogen isotope ratios was measured. Five different sources of TNT, compared for stable carbon and nitrogen isotope ratios, showed a range of 4.2 and 15%, respectively. This large range in the isotope ratios suggests excellent potential to trace sources in a complex environment. Finally, a site was surveyed for concentrations and isotope values of TNT extracted from groundwaters. Values from this site were substantially different relative to the variation measured on standards and in laboratory incubation experiments. The data set indicates good potential to use stable isotopes to determine TNT sources and fate in the environment. PMID- 11764150 TI - Factors affecting the occurrence and enantiomeric degradation of hexachlorocyclohexane isomers in northern and temperate aquatic systems. AB - Concentrations of (alpha- and gamma-hexachlorocyclohexane (HCH), alpha/gamma-HCH ratios, and enantiomer ratios (ER) of alpha-HCH were measured in lakes in the arctic, subarctic, Great Lakes, Canada, and temperate regions, and temperate and arctic wetlands and streams. The highest concentrations of alpha-HCH were found in cold, large, and oligotrophic lakes such as those in the arctic, subarctic, and the upper Great Lakes, which is attributed to greater inputs from atmospheric deposition and slower loss rates relative to warmer, temperate lakes. High alpha/gamma-HCH ratios in northern systems indicate aged HCH that has undergone long-range transport to high latitude areas, whereas low ratios in the lower Great Lakes and small temperate systems indicate recent gamma-HCH usage and residual alpha-HCH concentrations. Enantioselective degradation (ERs ranged from 0.31 to 0.7) was greatest in small, high arctic lakes and streams and in large lakes in the subarctic in which alpha-HCH concentrations and contact time between chemical and sediments are highest and nutrient concentrations are lowest. Low ERs were found in wetlands and streams in which contact between chemical and sediments was greatest. Conversely, minimal enantioselective degradation occurred in temperate small lakes and wetlands (ERs ranging from 0.77 to 1.06), despite the warmer temperatures, greater microbial populations, and nutrient availability. The results suggest that enantioselective degradation is optimized by maximal contact between chemical and sediment substrates in nutrient-poor waters in which, it is hypothesized, oligotrophic bacteria may act as biofilms. PMID- 11764149 TI - Structure-specificity relationships for haloalkane dehalogenases. AB - A structural analysis of the substrate specificity of hydrolytic dehalogenases originating from three different bacterial isolates has been performed using the multiple computer-automated structure evaluation methodology. This methodology identifies structural fragments in substrate molecules that either activate or deactivate biological processes. The analysis presented in this contribution is based on newly measured dehalogenation data combined with data from the literature (91 substrates). The enzymes under study represent different specificity classes of haloalkane dehalogenases (haloalkane dehalogenase from Xanthobacter autotrophicus GJ10, Rhodococcus erythropolis Y2, and Sphingomonas paucimobilis UT26). Three sets of structural rules have been identified to explain their substrate specificity and to predict activity for untested substrates. Predictions of activity and inactivity based on the structural rules from this analysis were provided for those compounds that were not yet tested experimentally. Predictions were also made for the compounds with available experimental data not used for the model construction (i.e., the external validation set). Correct predictions were obtained for 28 of 30 compounds in the validation set. Incorrect predictions were noted for two substrates outside the chemical domain of the set of compounds for which the structural rules were generated. A mechanistic interpretation of the structural rules generated provided a fundamental understanding of the structure-specificity relationships for the family of haloalkane dehalogenases. PMID- 11764151 TI - Photodegradation of hydroxychlorothalonil in aqueous solutions. AB - Hydroxychlorothalonil is the principal degradation product of the fungicide chlorothalonil in soil, and it is routinely detected in leachate from golf course greens at concentrations as high as 2 ppm. However, it is not detected in receiving waters of shallow ponds. Irradiation with simulated sunlight degraded hydroxychlorothalonil in distilled-deionized water, phosphate buffer, and pond water with half-lives of approximately 30 min. Slower degradation was observed in solutions of NaCl and NaCN, suggesting photonucleophilic substitution reactions may be responsible for the degradation. Hydroxylated products resulting from the displacement of chlorine and cyano groups were detected within the first hour of irradiation but were subsequently degraded to small aliphatic acids (succinic, oxalic, and malonic acid) within 96 h. Simulations of aquatic dissipation of the chemical using the U.S. Environmental Protection Agency standard pond scenario in the exposure analysis modeling system indicate that the 30-min half-life measured in the laboratory would equate to a half-life of 2.6 d in a 2-m-deep pond and as much as 3.4 d in seawater. Although hydroxychlorothalonil is moderately stable and mobile in soil, these data suggest that, in surface water, it should be rapidly degraded by sunlight to small aliphatic acids on transport into aquatic systems. PMID- 11764152 TI - Detection of environmental endocrine-disruptor effects on gene expression in live Rana catesbeiana tadpoles using a tail fin biopsy technique. AB - We describe a novel method of rapidly assessing exposure of premetamorphic Rana catesbeiana tadpoles to endocrine-disrupting chemicals. Tail fin biopsy and reverse transcription-polymerase chain reaction analyses of the thyroid hormone (TH)-responsive gene, TH receptor beta (TRbeta), demonstrate for the first time that a known accelerant of TH-induced metamorphosis, acetochlor, can significantly enhance TH-induced TRbeta mRNA levels within 24 h at an environmentally relevant dose. Although we focus on laboratory exposures in this study, this method easily can be adapted for use in field studies. PMID- 11764153 TI - Toxicity of linear alkylbenzene sulfonates and nonylphenol in sludge-amended soil. AB - The application of sewage sludge to agricultural land brings several chemicals to the soil ecosystem. Linear alkylbenzene sulfonates (LAS) and nonylphenol (NP) are frequently found in sludge at relatively high concentrations. The toxic effects of LAS and NP to two soil invertebrates (Folsomia candida and Enchytraeus albidus) and five different microbial processes (aerobic respiration, nitrification, denitrification, anaerobic CH4 production, and anaerobic CO2 production) were investigated in sludge-soil mixtures. Median lethal concentrations (LC50 values) and median effective concentrations (EC50 values) were quite similar and calculated to be in the range of 1,143 to 1,437 and 71 to 437 mg/kg (dry wt) for LAS and NP, respectively. The EC50 values for nitrification and CH4 production were 431 and 277 mg/kg, respectively, for LAS and 343 and 754 mg/kg, respectively, for NP. Aerobic respiration and denitrification were not inhibited at the tested concentrations. The results show that NP was more toxic than LAS to both F. candida and E. albidus, whereas LAS was more toxic than NP to the anaerobic CH4 production. The safety margins between the lowest 10% effective concentration (EC10) and the estimated environmental concentration were a factor of 11 for LAS and 510 for NP when the concentrations of the contaminants corresponded to the current Danish cutoff values of 1,300 mg/kg for LAS and 30 mg/kg for NP. PMID- 11764154 TI - Fate of atrazine and alachlor in redox-treated ferruginous smectite. AB - The oxidation state of structural iron (Fe) in clay minerals exerts a large influence on clay surface chemistry and may affect the adsorption and degradation of pesticides in the environment. This effect, however, has been little investigated. In the present study, herbicides atrazine and alachlor were reacted with ferruginous smectite (sample SWa-1) in its oxidized, reduced (either chemically or bacterially), and reduced-reoxidized states. In some experiments the herbicide was labeled with 14C. Gas chromatography/mass spectrometry (GC-MS) was also used to detect alachlor degradation products. Compared to oxidized clays, reduction by both chemical and microbial treatments decreased the concentration of both herbicides in the surrounding solution. Reoxidized clay exhibited behavior similar to the oxidized clay. Hydrolysis-dechlorination of atrazine occurred in the presence of chemically reduced SWa-1, and GC-MS analysis of alachlor revealed at least 14 degradation products after treatment with reduced clay and only two with the oxidized clay. Interaction of atrazine and alachlor with the clay may be through a H bond with the waters of hydration surrounding interlayer cations, the extent of which should increase with increasing acidity; but under reduced conditions, the validity of this model is unclear. Reduction of structural Fe may affect pH-dependent phenomena in two ways: The increased surface charge density increases the number of hydrated interlayer cations, thereby enhancing surface acidity, and increased electron density at basal surface oxygens increases their Bronsted basicity. Atrazine could, therefore, adsorb and/or degrade through either acid or alkaline hydrolysis pathways. Increased reduction potential of the reduced clay surfaces may also promote degradation. PMID- 11764155 TI - Biodegradation of bisphenol A in aquatic environments: river die-away. AB - The biodegradability of bisphenol A (BPA) was assessed in surface waters from seven different rivers across the United States and Europe. Rapid biodegradation of BPA was observed in all rivers following lag phases ranging from 2 to 4 d. Biodegradation half-lives for BPA were typically less than 2 d following the lag phase. Mineralization of BPA was observed in all river waters, with average carbon dioxide yields of approximately 76% of the theoretical maximum (range 59 103%) at the end of the incubation period (< or = 18 d). Short half-lives (0.5 to 3 d) were noted for BPA biodegradation in river waters regardless of geographic location, sampling site (i.e., upstream vs downstream of wastewater outfalls), sediment addition (< or = 0.05%), and initial test chemical concentration (50 5,500 microgram/L). Subsequent studies conducted at environmentally relevant concentrations (0.05 and 0.5 microgram/L) also indicated short half-lives (3-6 d) for BPA and support the extrapolation of the half-lives measured in this study over a wide range of environmental concentrations. The fact that BPA was degraded rapidly in surface waters taken from diverse locations in the United States and Europe as well as in studies recently conducted in Japan suggests that BPA degrading microorganisms are widely distributed in nature. These observations provide clear evidence that BPA is not persistent in the aquatic environment. PMID- 11764156 TI - Aryl hydrocarbon receptor-mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments. AB - Reproductive dysfunction in wildlife populations can be a result of environmental contaminants binding to aryl hydrocarbon receptor (AhR) or estrogenic receptors. Signaling by both types of receptors can be affected by polycyclic aromatic hydrocarbons (PAHs), which are potential endocrine disruptors. However, our knowledge regarding the effects of oxygenated (oxy)-PAHs and azaarenes on AhR mediated and estrogenic activities is incomplete. In the present study, we have identified 9-fluorenone, anthrone, anthraquinone, benzanthrone, benz[a]anthracene 7,12-dione, benz[c]acridine, and dibenz[a,h]acridine as prevalent oxy-PAHs and azaarenes found in river sediments. Their concentrations in sediment samples ranged from 2.1 to 165.2 ng g(-1) for oxy-PAHs and up to 27.3 ng g(-1) for azaarenes. Their relative AhR-inducing and estrogenic potencies were quantified in vitro using two cell lines that were stably transfected with a luciferase reporter gene system and expressed as induction equivalency factors (IEFs). The only oxy-PAHs with detectable levels of in vitro AhR-mediated activity were benzanthrone and benz[a]anthracene-7,12-dione. However, their IEFs were approximately three to four orders of magnitude lower than those of benzo[a]pyrene. On the other hand, azaarenes showed a strong AhR-mediated activity, with dibenzo[a,h]acridine being a far more potent inducer of activity than benzo[a]pyrene. Benzanthrone, benz[a]anthracene-7,12-dione, anthraquinone, and benz[a]acridine were weak inducers of in vitro estrogenic activity, with IEFs similar to that of benzo[a]pyrene. Based on concentrations and relative potencies, our results suggest that dibenzo[a,h]acridine can significantly contribute to the overall AhR-mediated activity in river sediments, whereas the remaining compounds do not. No studied compound was found to contribute significantly to estrogen receptor-mediated activity in vitro. PMID- 11764157 TI - Butyltin compounds in sediments from the commercial harbor of Alexandria City, Egypt. AB - Tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) compounds were quantitatively determined in surface-sediment samples collected from 23 sites in the commercial harbor of Alexandria City, Egypt. Butyltin concentrations in sediments varied widely depending on the sample location, ranging from less than 0.1 to 186 ng g(-1) of Sn for MBT, less than 0.1 to 379 ng g(-1) of Sn for DBT, and 1 to 2,067 ng g(-1) of Sn for TBT Elevated TBT concentrations, ranging from 727 to 2,067 ng g(-1) of Sn were observed in harbors, marinas, and near ship repair facilities, indicating that the butyltin-containing, antifouling paints of boats and vessels are the major source of butyltin contamination. The TBT concentration decreased rapidly away from potential source areas of boat docking and repair facilities. The high relative concentrations of TBT in the sediments indicated that degradation processes in the sediments are minor, probably due to the anoxic sedimentary conditions at the sampling sites and/or relatively fresh input of TBT to these sites. PMID- 11764158 TI - Relationship between soil copper content and copper content of selected crop plants in central Chile. AB - A survey of copper levels in agricultural soils of central Chile revealed two soil clusters-one with a mean copper level of 162 mg/kg and one with a mean copper level of 751 mg/kg of soil. Samples of soils from both soil clusters were characterized on the basis of physicochemical characteristics, and copper extractability was compared by saturation and CaCl2 extraction as well as an acid leaching procedure (TCLP). We also measured the copper content of various tissues of tomato (Lycopersicon esculentum) and onion (Allium cepa) crops growing on these soils. Other than copper levels, soils from the two clusters were quite similar, with slightly greater levels of molybdenum and cadmium in the high copper soils. Within each cluster, extracted copper levels and total soil copper levels were not correlated. However, the three extraction procedures solubilized significantly more copper from the high-Cu soils. Mineralogical characterization of the soil particles and depth profiles of soil metal levels in a subsample of sites suggested that highly insoluble copper ore and mining wastes might account for the high copper levels. Neither total nor extractable copper levels allowed statistical prediction of the levels of copper in plant tissue. The edible tissues of both crops had the same mean copper content, regardless of the copper soil level. However, copper contents of stems and leaves were significantly higher for plants growing on the high-Cu soils. These results show that in these soils, high copper levels are associated with very insoluble copper species and thus low bioavailability of copper to crop plants. PMID- 11764159 TI - Chlorodifluoroacetic acid fate and toxicity to the macrophytes Lemna gibba, Myriophyllum spicatum, and Myriophyllum sibiricum in aquatic microcosms. AB - Chlorodifluoroacetic acid (CDFA) is a novel haloacetic acid (HAA) and has been recently documented in aquatic systems. It is a suspected degradation product of the refrigerants 1,1,2-trichloro-1,1-difluoroethane (CFC-113) and 1-chloro-1,1 difluoroethane (HCFC-142b). Haloacetic acids can be phytotoxic, putatively acting through inhibition of the citric acid cycle. Replicate (n = 3) 12,000-L model aquatic ecosystems (microcosms) were dosed once at 0.5, 1, 5, and 20 mg/L of neutralized CDFA. Three microcosms served as controls. Each microcosm was stocked with eight individual apical shoots of both Myriophyllum spicatum and Myriophyllum sibiricum and sampled at regular intervals over a 42-d exposure period. The plants were assessed for the somatic endpoints of plant length, root growth, node number, and wet and dry mass and the biochemical endpoints of chlorophyll-a/b and carotenoid content as well as citric acid levels. The duckweed Lemna gibba was also introduced into these systems and monitored over a period of 14 d for wet/dry mass, plant/frond number, chlorophyll content, and growth rate. Concentrations of CDFA remained constant in the water column over the course of the fate investigation (241 d), indicating that this compound undergoes little, if any, degradation in aquatic systems. Results showed few statistically significant differences from controls for all three plant species with exposure to CDFA but no biologically relevant impacts. Overall, CDFA does not appear to pose any risk to these aquatic macrophytes at current environmental concentrations. PMID- 11764160 TI - Characterization of dioxin-like activity of sediments from a Czech river basin. AB - Synthetic organic chemicals are present in environmental compartments as complex mixtures and therefore their potential effects are difficult to predict. In this study, in vitro bioassays using wild-type fish and rat hepatoma cell lines and their corresponding recombinant cell systems were used to evaluate 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-like activity in extracts of sediments collected from rivers of the Czech Republic. All the sediment extracts elicited statistically significant responses in all the cell lines tested. For most sediment extracts, a complete dose-response relationship was obtained. The maximal efficacy of the samples was between 57 and 143% of the maximal induction elicited by TCDD. Greater responsiveness, sensitivity, and reproducibility were observed for recombinant than wild-type cells. Cell line-specific differences in the sensitivity to compounds present in the complex sediment extracts were observed. The TCDD equivalents (TCDD-EQs) determined from the different cell bioassays were correlated. Greater concentrations of TCDD-EQs were obtained with fish cell lines. The TCDD-EQs calculated from the results of chemical analysis of toxic equivalents (TEQs) were in good agreement with those determined by bioassays; the arly hydrocaron receptor (AhR)-effects of the identified chemicals appear to be generally additive. This indicates that most of the TCDD-like activity was accounted for by the compounds identified and quantified by instrumental analysis. Fractionation along with mass-balance calculations allowed identification of the active fractions and classes of compounds. Polycyclic aromatic hydrocarbons (PAHs) were found to be responsible for most of the AhR mediated activity in sediments. PMID- 11764161 TI - Temperature- and parasite-induced changes in toxicity and lethal body burdens of pentachlorophenol in the freshwater clam Pisidium amnicum. AB - Seasonal variation in abiotic and biotic environments may modify the toxicity of organic chemicals for aquatic organisms. In present study, survival of the freshwater clam Pisidium amnicum was studied in laboratory exposures to pentachlorophenol (PCP) in April (at 5 degress C) and July (at 19 degress C). Behavioral responses, mean survival times (MSTs), and the lethal body burdens (LBBs) of PCP for uninfected clams and for clams infected by digenean trematodes were determined separately in two PCP concentrations, 100 and 300 microgram/L. Analysis of data revealed reduced behavioral activity of the clams in the PCP exposure compared to that in the control. The time needed for toxic responses was greatly affected by temperature; MSTs were 5 to 15 times longer in winter than at summer temperatures. Unexpectedly, the infected clams in summer were more tolerant to PCP than the uninfected clams. Despite the differences in survival times, the LBBs between the seasons were constant. However, in summer, the infected clams had significantly higher LBBs than the uninfected clams. The differences in survival and LBBs between the infected and uninfected clams are suggested to be caused by the high lipid contents found in parasites, which may change the internal distribution of PCP. PMID- 11764162 TI - Response of phytoplankton communities to liquid creosote in freshwater microcosms. AB - We assessed the response of phytoplankton communities in aquatic microcosms to single applications of liquid creosote. The creosote was applied to 14 microcosms at concentrations ranging from 0.06 to 109 mg/L. Two microcosms served as controls. Phytoplankton samples were collected from each microcosm one week and 1 d before treatment and at 7 and 21 d after treatment. Temporal changes (response recovery) in phytoplankton community composition were assessed with principal response curves. Creosote had no direct toxic effect on the phytoplankton community based on total abundance and number of taxa. Population levels declined in all treatments between day -1 and day 7, but this trend mirrored a similar decline in the control microcosms. At both 7 and 21 d after treatment, population densities and number of taxa in most treatments exceeded those in the controls and exhibited a parabolic relationship relative to creosote concentration. This relationship was most pronounced at 21 d, at which time population densities and number of taxa at intermediate concentrations were up to twice those at low and high concentrations. This response pattern seems to represent an indirect response to impacts on zooplankton and a corresponding reduction in grazing pressure. In contrast, total algal biomass declined 52 to 97% relative to the controls at all but the lowest creosote concentration at 7 d. This apparent decline was due to a significant proliferation of the alga Closterium moniliforme in the controls and low creosote concentration. At 21 d, no difference was found in total biomass between treated and control microcosms. The results of this study suggest that creosote does not pose a significant direct risk to phytoplankton at concentrations likely to be encountered in most contaminated aquatic environments; however, stimulation of algal populations could occur in situations of long-term chronic exposure or spill events that remove predatory zooplankton populations. PMID- 11764163 TI - Toxicity of cadmium to Caenorhabditis elegans (Nematoda) in whole sediment and pore water--the ambiguous role of organic matter. AB - A bioassay using the nematode Caenorhabditis elegans was performed with natural sediment that had been spiked with organic matter (36-117 g total organic carbon/kg dry wt) and cadmium (Cd; 10-1,200 mg/kg wet wt). Whole sediment and pore water were tested to study the influence of particulate organic matter (POM) and dissolved organic matter (DOM) on Cd toxicity and to compare the toxicity of the two sediment phases. Toxicity was measured with nematode growth as test parameter. No toxicity was observed if sediment concentrations of Cd were below concentrations of acid-volatile sulfides (AVS). At higher Cd concentrations, toxicity in whole sediment and pore water increased with increasing organic content. This phenomenon was explained by an increase of DOM concentrations in organically enriched treatments and a resulting solubilization of Cd due to Cd complexation by DOM. Because DOM did not alter the bioavailability of Cd for the nematodes, bacteria, serving as food, might have functioned as vectors for Cd-DOM complexes, so that Cd could have become available in the gut of the nematodes. A higher toxicity in whole sediment compared to in pore water in the organically enriched treatments indicated that POM-bound Cd may have contributed to the toxicity of Cd to C. elegans. PMID- 11764164 TI - Trace element accumulation in hawksbill turtles (Eretmochelys imbricata) and green turtles (Chelonia mydas) from Yaeyama Islands, Japan. AB - Concentrations of 18 trace elements (V, Cr, Mn, Co, Cu, Zn, Se, Rb, Sr, Zr, Mo, Ag, Cd, Sb, Ba, Hg, Tl, and Pb) were determined in the liver, kidney, and muscle of green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) from Yaeyama Islands, Okinawa, Japan. Accumulation features of trace elements in the three tissues were similar between green and hawksbill turtles. No gender differences in trace element accumulation in liver and kidney were found for most of the elements. Significant growth-dependent variations were found in concentrations of some elements in tissues of green and hawksbill turtles. Significant negative correlations (p < 0.05) were found between standard carapace length (SCL) and the concentrations of Cu, Zn, and Se in the kidney and V in muscle of green turtles and Mn in the liver, Rb and Ag in kidney, and Hg in muscle of hawksbill turtles. Concentrations of Sr, Mo, Ag, Sb, and Tl in the liver, Sb in kidney, and Sb and Ba in muscle of green turtles and Se and Hg in the liver and Co, Se, and Hg in kidney of hawksbill turtles increased with an increase in SCL (p < 0.05). Green and hawksbill turtles accumulated extremely high concentrations of Cu in the liver and Cd in kidney, whereas the levels of Hg in liver were low in comparison with those of other higher-trophic-level marine animals. High accumulation of Ag in the liver of green turtles was also observed. To evaluate the trophic transfer of trace elements, concentrations of trace elements were determined in stomach contents of green and hawksbill turtles. A remarkably high trophic transfer coefficient was found for Ag and Cd in green turtles and for Cd and Hg in hawksbill turtles. PMID- 11764165 TI - Heavy metals and selenium in feathers of great tits (Parus major) along a pollution gradient. AB - We evaluated the use of great tit (Parus major) feathers as biomonitors for heavy metal pollution and tested whether there were differences in metal levels in feathers as a function of location, age (first year or older), or gender. In 1998 and 1999, we collected the outermost tail feathers of 185 great tits from four sites along a presumed pollution gradient and one reference site in Antwerp (Belgium) and analyzed them for calcium, selenium, and 13 heavy metals (silver, aluminum, arsenic, cadmium, cobalt, chromium, copper, iron, mercury, manganese, nickel, lead, and zinc). Silver, arsenic, cadmium, cobalt, copper, mercury, nickel, lead, selenium, and zinc concentrations were significantly higher closest to the pollution source (UM site) compared with the other four sites. Heavy-metal and selenium levels were on average 2 to 40 times higher at the UM site compared with the reference site. Aluminum, calcium, and iron levels were not significantly different among sites. We found no general age- or gender-related differences in metal levels except for arsenic and iron, where a significant interaction between site and gender was observed. Our results suggest that feathers of great tits might be useful biomonitoring tools because they reflect the environmental contamination by heavy metals well. PMID- 11764166 TI - Development of copepod nauplii to copepodites--a parameter for chronic toxicity including endocrine disruption. AB - Test compounds including natural hormones, endocrine disrupters, environmentally occurring compounds, and reference compounds were tested for acute toxicity and inhibitory effect on larval development in the copepod Acartia tonsa. Three compounds, 17alpha-ethinylestradiol, p-octylphenol, and tamoxifen, known for their differing effects on the vertebrate estrogen system, were potent inhibitors of naupliar development. Other estrogens, 17beta-estradiol, estrone, and bisphenol A, had little potency. Testosterone and progesterone did not inhibit development, but the antiandrogen flutamide had inhibitory effect. Juvenile hormone III was a potent inhibitor, as was expected based on the literature, whereas 20-hydroxyecdysone had no effect. 3,4-Dichloroaniline was inhibitory on development, whereas other control compounds, potassium dichromate and 3,5 dichlorophenol, did not inhibit development. Six of the 17 test compounds had 50% lethal concentration to 50% effective concentration (EC50) ratios higher than 10. The results suggest that naupliar development, as a parameter, is able to detect hormonal disrupters in addition to other chemicals that have other specific modes of action. PMID- 11764167 TI - Subchronic exposure of BALB/c and C57BL/6 strains of Mus musculus to the radioactive environment of the Chornobyl, Ukraine exclusion zone. AB - Environmental contamination resulting from the Chornobyl, Ukraine, disaster offers a unique opportunity to examine the in vivo biological effects of chronic, low-dose exposure to radiation. Laboratory studies of acute exposure to ionizing radiation have been used to estimate risk and potential human health effects by the extrapolation of laboratory data to situations of low-dose environmental radiation exposure. Few studies, however, have explored the biological consequences of low-dose exposure via in situ environmental radiation in a sentinel species. In the present study, laboratory strains of Mus musculus (BALB/c and 57BL/6) were placed in environmental enclosures in the Red Forest region of the Chornobyl exclusion zone. Blood samples were obtained every 10 d, and the micronucleus (MN) test was employed to assess the potential for cytogenetic damage from exposure to Chornobyl radiation. Radionuclide uptake was monitored throughout the study, and dose was estimated for each individual as well as for their offspring. Total dose for the mice experimentally exposed to this environment averaged 1,162 mGy for BALB/c (30 d) and 1,629 mGy for C57BL/6 (40 d). A higher MN frequency for both strains was observed at day 10, although this change was only statistically significant in the C57BL/6 mice (chi2/3 = 13.41, p = 0.003). Subsequent samples from C57BL/6 resulted in values at or less than the initial frequencies. In BALB/c mice, an increase in MN was also evident at day 30 (chi2/3 = 10.38, p = 0.006). The experimental design employed here allows for the incorporation of traditional laboratory strains, as well as transgenic strains of Mus, as sentinels of environmental radiation contamination. PMID- 11764168 TI - Effects of bisphenol A and tetrabromobisphenol A on sex organ development in quail and chicken embryos. AB - The plastic monomere bisphenol A (BPA) and the flame retardant tetrabromobisphenol A (TBBPA) were examined for estrogen-like developmental effects on the reproductive organs in avian embryos. The synthetic estrogen diethylstilbestrol (DES) was used as a positive control. The test compounds were injected into the yolk of quail and chicken eggs early during incubation and the embryos were examined 2 d before anticipated hatching. At 200 microgram/g egg, BPA induced Mullerian duct (embryonic oviduct) malformation in female quail embryos and feminization of the left testis (ovotestis) in male chicken embryos. The estrogenic potency of BPA compared with DES was species and endpoint specific. Mullerian duct malformation was the most sensitive endpoint in quail embryos, whereas ovotestis formation was the most sensitive response in chicken embryos. Tetrabromobisphenol A caused high embryo mortality at 45 microgram/g egg in both species, but no estrogen-like effects were observed. Bisphenol A caused mortality only in chicken embryos at 67 and 200 microgram/g egg. To our knowledge, this is the first report on estrogen-like or embryolethal effects of BPA and TBBPA in birds. PMID- 11764169 TI - Sexual disruption in a second species of wild cyprinid fish (the gudgeon, Gobio gobio) in United Kingdom freshwaters. AB - To establish whether the intersex condition seen in the roach (Rutilus rutilus) in United Kingdom (UK) rivers was species specific or a more general phenomenon in fish, evidence for sexual disruption was sought in a second cyprinid species, the gudgeon (Gobio gobio). Gudgeon were collected from the Rivers Aire and Lea (at locations that receive high-volume discharges of sewage treatment works [STW] effluent and that contain intersex roach) and from two still waters, and their gonads were examined histologically for evidence of intersexuality (the simultaneous presence of oocytes and testicular tissue). Intersex gonads were found at all sites, with the highest incidences occurring at one of the still waters (Lakeside Fisheries: 15%) and at sites on the River Aire (Thwaite Weir, Silsden Bridge, and Knostrop: 14, 13, and 12%, respectively). In the River Lea and Longton Park Lake, the incidence of intersexuality in gudgeon was 6%. In most cases, intersex gonads were characterized by a few primary oocytes/gonad section in an otherwise normal testis. However, at some sites on the River Aire (Thwaite Weir and Knostrop), the intersex condition was more severe. At Thwaite Weir, for example, more than half of the gonad in 40% of the intersex fish was comprised of ovarian tissue. Elevated concentrations of plasma vitellogenin both in male and in intersex fish indicated that fish had been exposed to estrogen(s). Some of the gudgeon were found at sites several kilometers downstream of any point discharge of STW effluent; therefore, the results likely are representative of this species in wild populations found in typical UK river ecosystems. Together with the findings in the roach, these data on the gudgeon confirm that sexual disruption in fish in UK rivers is not species specific. PMID- 11764170 TI - Dicofol residues in eggs and carcasses of captive American kestrels. AB - American kestrels (Falco sparverius) were fed diets containing 0 (control), 1, 3, 10, and 30 microgram/g (wet wt) of Kelthane. Residues of dicofol and its metabolites were then analyzed in the eggs and carcasses of females. Significant differences occurred among treatments for residues of both p,p'-dicofol and p,p' dechlorodicofol (DCD) in both eggs and carcasses and for p,p' dicholorbenzophenone (DCBP) in eggs. Residue concentrations increased with increasing treatment exposure. Residues of p,p'-dicofol, p,p'-DCD, and p,p'-DCBP in eggs were significantly correlated with eggshell quality parameters. Significant correlations also occurred among contaminants in eggs and for individual contaminants between eggs and carcasses. The lowest-observed-dietary effect concentration for eggshell thinning was 3 microgram/g, whereas 1 microgram/g may be considered to be near a no-observable-adverse-effect concentration. Concentrations of dicofol in potential prey items and eggs of wild birds generally have been lower than dietary-effect concentrations or concentrations in tissues or eggs associated with eggshell thinning and reduced reproductive success. PMID- 11764171 TI - Use of Ulva lactuca to identify ammonia toxicity in marine and estuarine sediments. AB - Toxicity identification evaluation (TIE) methods are being developed for use with whole sediments. Although a phase I TIE method has been developed to characterize ammonia toxicity in aqueous samples using the marine macroalga Ulva lactuca, the relationship between amphipod and mysid mortality and uptake by U. lactuca of bedded sediment ammonia had not been explored. Additionally, it was not known how interactions in whole sediments between metal and organic contaminants with U. lactuca and ammonia would affect TIE interpretation. The current study showed that ammonia toxicity to amphipods and mysids was reduced significantly in marine sediments in the presence of U. lactuca. The alga slightly affected metal concentrations but did not alter the concentration of organic contaminants in either overlying or interstitial waters. Conversely, ammonia uptake by U. lactuca was not affected by the presence of metal or organic contaminants in the sediments. When used with other TIE manipulations, U. lactuca can be utilized in a whole-sediment, phase I TIE to remove toxicity due to ammonia. PMID- 11764172 TI - Lead poisoning in the globally threatened marbled teal and white-headed duck in Spain. AB - Marbled teal (Marmaronetta angustirostris) and white-headed duck (Oxyura leucocephala) are the two European ducks threatened with global extinction. We investigated lead (Pb) poisoning in stifftails (Oxyura spp., n = 83) and marbled teal (n = 80) shot or found dead or moribund in Spanish wetlands via gizzard examination and liver, bone, and blood Pb analysis. Ingested Pb shot was present in 32% of shot stifftails and 70 and 43% of dead or moribund stifftails and marbled teal, respectively. Lead-shot ingestion was more frequent in Valencia (eastern Spain), where Pb-shot densities were higher and grit scarcer. Selection of larger grit similar in size to Pb shot may explain the higher rate of Pb-shot ingestion observed in stifftails. Ingested shot was found more frequently in juvenile stifftails than in adults. Lead bone concentrations were higher in ducklings < 9 d old than in fully grown teal and were also higher in adult than in juvenile teal. Our results show the need for a ban of Pb shot for waterfowl hunting in Spain and the cleanup of spent shot at major wetlands. PMID- 11764173 TI - Contaminant sensitivity of threatened and endangered fishes compared to standard surrogate species. AB - Standard environmental assessment procedures are designed to protect terrestrial and aquatic species. However, it is not known if endangered species are adequately protected by these procedures. At present, toxicological data obtained from studies with surrogate test fishes are assumed to be applicable to endangered fish species, but this assumption has not been validated. Static acute toxicity tests were used to compare the sensitivity of rainbow trout, fathead minnows, and sheepshead minnows to several federally listed fishes (Apache trout, Lahontan cutthroat trout, greenback cutthroat trout, bonytail chub, Colorado pikeminnow, razorback sucker, Leon Springs pupfish, and desert pupfish). Chemicals tested included carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin. Results indicated that the surrogates and listed species were of similar sensitivity. In two cases, a listed species had a 96-h LC50 (lethal concentration to 50% of the population) that was less than one half of its corresponding surrogate. In all other cases, differences between listed and surrogate species were less than twofold. A safety factor of two would provide a conservative estimate for listed cold-water, warm-water, and euryhaline fish species. PMID- 11764174 TI - Joint acute toxicity of diazinon and ammonia to Ceriodaphnia dubia. AB - Diazinon is an organophosphorous pesticide widely found in municipal effluents as well as in agricultural and urban storm-water discharges. Ammonia is frequently also present in such effluents as a consequence of bacterial degradation of organic material. Because these two contaminants may occur concurrently, their relationship with respect to joint toxicity is of interest, particularly in regard to interpreting the results of effluent tests and subsequent toxicity identification evaluations (TIEs). In this particular case, we obtained an effluent sample that exhibited toxicity to Ceriodaphnia dubia. Toxicity identification evaluations manipulations suggested that ammonia (40 mg?L as total NH3) and diazinon (0.75 microgram/L) both contributed to toxicity. As part of the Phase 3 confirmation studies, an independent investigation was conducted to evaluate the interactions between these two toxicants using static tests that incorporated a 48-h exposure period. Chemical concentrations were verified analytically. Mortalities were measured at 24-h intervals and joint toxicity calculated on the basis of toxic units (TUs) for each toxicant. The 48-h LC50 values (lethal concentrations for 50% of the population) for the individual chemicals averaged 0.36 microgram/L and 1.11 mg/L for diazinon and un-ionized ammonia, respectively. Under the assumption of strict additivity, the sum of TUs contributed by each toxicant at the LC50 of the mixture should total unity. The TUs associated with the mixtures in laboratory water averaged 1.37 and 1.47, respectively, for 24- and 48-h exposure intervals. These results were similar to those obtained with the actual effluent sample and suggest that diazinon and ammonia exhibit less than additive toxicity when present together. PMID- 11764175 TI - Evaluation of bioassays versus contaminant concentrations in explaining the macroinvertebrate community structure in the Rhine-Meuse delta, The Netherlands. AB - It is often assumed that bioassays are better descriptors of sediment toxicity than toxicant concentrations and that ecological factors are more important than toxicants in structuring macroinvertebrate communities. In the period 1992 to 1995, data were collected in the enclosed Rhine-Meuse delta, The Netherlands, on macroinvertebrates, sediment toxicity, sediment contaminant concentrations, and ecological factors. The effect of various groups of pollutants (polycyclic aromatic hydrocarbons, trace metals, oil, polychlorinated biphenyls) and of ecological variables on the structure of the macroinvertebrate community were quantified. Ecological factors explained 17.3% of the macroinvertebrate variation, while contaminants explained 13.8%. Another 14.7% was explained by the covariation between ecological variables and contaminants. Polycyclic aromatic hydrocarbons explained a larger part of the variation than trace metals. The contributions of oil and polychlorinated biphenyls were small but significant. Elevated contaminant concentrations were significantly associated with differences in the macroinvertebrate food web structure. The response in bioassays (Vibrio fischeri, Daphnia magna, Chironomus riparius) was susceptible to certain contaminants but also to certain ecological factors. There was a weak correlation between in situ species composition and bioassays; 1.9% of in situ macroinvertebrate variation was explained by the bioassay responses. This seems to contradict the validity of using bioassays for a system-oriented risk assessment. Possible reasons for this discrepancy might be the manipulations of the sediment before the test and a higher pollutant tolerance of the in situ macroinvertebrates. Thus, macroinvertebrate field surveys and laboratory bioassays yield different types of information on ecotoxicological effects, and both are recommended in sediment risk assessment procedures. PMID- 11764176 TI - The presence of chemicals exuded by fish affects the life-history response of Ceriodaphnia cf. dubia to chemicals with different mechanisms of action. AB - The toxicity of chemicals with different mechanisms of action (3,4 dichloroaniline, fenoxycarb, and chlorpyrifos) to the cladoceran Ceriodaphnia cf. dubia was examined in the presence and absence of chemicals exuded by fish, termed fish kairomones. A range of life-history traits were examined, including mean brood sizes, survival, net reproductive rate (Ro) and population growth rate (r). Cladocerans exposed to 3,4-dichloroaniline showed similar sensitivities in the presence and absence of fish kairomones with respect to all of the life history traits examined. The presence of fish kairomones reduced the sensitivity of cladocerans to fenoxycarb with respect to mean brood sizes and r but increased their sensitivity in terms of Ro. The presence of fish kairomones increased the sensitivity of cladocerans to chlorpyrifos with respect to survival, r, Ro, and mean brood sizes. The general trends observed were similar to those shown when C. cf. dubia was exposed to these chemicals under low food conditions, and it is suggested that the effects of fish kairomones on toxicity may be attributed to the reduction in feeding rates observed when C. cf. dubia is exposed to fish kairomones. PMID- 11764177 TI - Effects of polycyclic aromatic compounds on the drought tolerance of Folsomia fimetaria (Collembola, Isotomidae). AB - Drought tolerance (survival at 98.2% relative humidity and 20 degress C) was investigated for adult individuals of the springtail Folsomia fimetaria after three weeks of exposure to different polycyclic aromatic compounds (PACs). Seven PACs were investigated (acridine, dibenzofuran, carbazole, fluorene, dibenzothiophene, fluoranthene, and pyrene), with each substance used at several exposure concentrations. Sublethal concentrations of dibenzothiophene, fluorene, fluoranthene, and pyrene caused a dose-related decrease in drought tolerance in exposed adults, whereas no such relationship was found for acridine, dibenzofuran, and carbazole. The organisms used in the drought tolerance study were taken directly from standard ecotoxicity tests that had just been completed, hence the concentrations causing subsequent effects on drought tolerance and those affecting survival and reproduction in the ecotoxicity tests could be compared. Some of the tested substances significantly reduced the drought tolerance of F. fimetaria at concentrations that had little effect on survival, indicating a synergistic effect of the two stressors. However, drought tolerance was affected at concentrations below the threshold value for toxicity in standard tests (no-observed-effect concentration for reproduction) only for dibenzothiophene. In the field, soil organisms exposed to contaminants also face multiple environmental stressors such as drought and cold. Because the reduced drought tolerance is a side effect of chemical exposure, such effects should be considered when extrapolating from laboratory to field conditions. PMID- 11764178 TI - Accumulation of DDT and mercury in prothonotary warblers (Protonotaria citrea) foraging in a heterogeneously contaminated environment. AB - Foraging areas of adult prothonotary warblers (Protonotaria citrea) were determined using standard radiotelemetry techniques to determine if soil concentrations of p,p'dichlorodiphenyltrichloroethane (p,p'DDT) and mercury in foraging areas could be used to predict contaminant levels in diets and tissues of nestling warblers. Adult warblers were fitted with transmitters and monitored for approximately 2 d while foraging and feeding 6- to 8-d-old nestlings. Foraging ecology data were integrated with contaminant levels of soil, diets, and tissues into a comprehensive analysis of geographic variation in contaminant exposure and uptake using linear regression. Concentrations of 1,1-dichloro-2,2 bis(p-chlorophenyl)ethylene (DDE) and mercury in nestling tissues varied considerably across the study site. Mean concentration of DDE was greater in eggs than all other tissues, with individual samples ranging from 0.24 to 8.12 microgram/kg. In general, concentrations of DDT in soil were effective in describing the variation of contaminants in adipose samples. Concentrations of mercury in soils accounted for 78% of the variation in kidney samples. This was the best relationship of any of the paired variables. All other relationships showed relatively poor predictive ability. PMID- 11764179 TI - Modeling pentachlorophenol bioavailability and bioaccumulation by the freshwater fingernail clam Sphaerium corneum using artificial particles and humic acids. AB - The uptake of anthropogenic chemicals by benthic bivalves may occur through the water phase and also by the ingestion of particles from both the suspended matter and bottom sediments. Many chemicals sorb to sediments and, subsequently, are released in the digestive tract of animals. The assessment of sediment-bound chemicals has been difficult because of the complexity of the association between these chemicals and natural particles. To simplify this complexity, we previously devised a test system using artificial particles with known chemical structures. In the present work, we improved this experimental design by adding humic materials as a source of organic matter. Bioassays were conducted by exposing the fingernail clam Sphaerium corneum to sublethal levels of pentachlorophenol (PCP) in the presence or absence of the artificial particles, treated with or without a commercial preparation of humic acids. The results showed that the bioavailability and bioaccumulation could be explained on the basis of the interactions of PCP with the active groups and/or the backbone of the resins, both in systems with or without humic acids. This model may constitute a useful approach to modeling and predicting the uptake and accumulation of chemicals bound to natural sediments. PMID- 11764180 TI - What's new in...neurogenetics? Focus on neurodegenerative disorders. PMID- 11764181 TI - Xeroderma pigmentosum/cockayne syndrome complex: first neuropathological study and review of eight other cases. AB - This is the first detailed description of the neuropathology of a patient with xeroderma pigmentosum/Cockayne syndrome complex (XP/CS). This 6-year-old boy's clinical course, followed from infancy to death, is compared with that of the eight other known cases of XP/CS. Normal at birth, he developed the cutaneous sun sensitivity of XP in infancy and the infantile CS phenotype in early childhood. He had the characteristic CS facies, cachexia, failure of somatic and brain growth, spasticity, ataxia, pigmentary retinopathy, hearing loss, mixed peripheral neuropathy, and myopathy. Like his clinical phenotype, the neuropathology was also that of CS despite an XPG genotype. His brain weighed 350 grams (considerably less than the expected weight at birth) and revealed hydrocephalus, tigroid-type demyelination, dystrophic calcification and widespread neuronal loss and gliosis with hyperchromatic glial and endothelial nuclei. Peripheral nerve showed myelinopathy with axonal degeneration, and skeletal muscle had mixed myopathic and neuropathic features. Ophthalmic pathology disclosed cataracts, iris and ciliary body atrophy, inner retinal atrophy and gliosis, retinal pigment epithelial atrophy, and optic nerve atrophy. Molecular studies, which have appeared elsewhere, do not provide full understanding of the pathophysiology of the postnatal growth failure, cachexia, precocious aging, selectivity of tissues affected (such as myelinated axons), and other manifestations of this devastating illness. PMID- 11764182 TI - Frontal absences in children. AB - In a cohort of 59 consecutive children referred for staring spells, we analysed clinical and electroencephalogram (EEG) characteristics in 23 children with both a history of absence seizures and a generalized spike and wave pattern during long-term video EEG monitoring. In 10 children, a frontal spike preceded the generalized spike and wave pattern. In the remaining 13 children, primary generalized spikes and waves were found. The frontal onset absences were clinically not different from primary generalized absences. The most striking difference between the two groups was the difficulty in controlling the absences in the frontal onset group and the high incidence of learning and behavioural problems in that group. The EEG analysis showed interictal, isolated epileptic discharges in 80% of the children with frontal onset absences. We believe that frontal onset absences should be considered as a secondarily generalized epilepsy syndrome, originating in the frontal regions. PMID- 11764183 TI - Neurodevelopmental and behavioural characteristics in learning disabilities and attention deficit disorder. AB - Specific learning disability in childhood is frequently associated with attention deficit disorder. The distinction between children with and without such comorbidity is often difficult to make. Our aim was to delineate the neurocognitive and behavioural differences between children with specific learning disabilities, with and without attention deficit. Students diagnosed with learning disability, mean age 8.3, 1.4 SD (N-50), and students with learning disability and attention deficit disorder, mean age 8.7, 1.4 SD (N-50), were assessed. The Paediatric Early Elementary Examination and the Aggregate Neurobehavioural Student Health Education Review were administered and their scores as well as pattern of correlations within and between domains were analysed. Only few differences in neurocognitive functions between these groups were evident. Most neurocognitive domains were similarly intercorrelated in the two groups. However, recall was correlated with other neurocognitive domains only among the children with learning and attention deficits. A proportion of significant correlations between neurocognitive and behavioural domains was found among the children with learning disability and attention deficit disorder, but not among the children with learning disability only. It appears that while neurocognitive profiles are similar in these two groups, their interrelationship with behavioural patterns differ. These findings give support to the neurological origin of attention deficit disorder related behaviours among learning disabled children. Different interventions should therefore be considered for each of these entities. PMID- 11764184 TI - Lack of association between childhood stroke after varicella and human leukocyte antigen (HLA)-B51. AB - Human leukocyte antigen (HLA)-B51 has been suggested as an immunogenetic marker for a genetic predisposition to vascular occlusion in response to an immunological stimulus. Varicella has been reported to be a possible risk factor for stroke. We performed DNA-based HLA typing in 11 young patients (mean age: 5.2 years) with unexplained ischaemic stroke. In eight of them varicella had occurred before their stroke. HLA-B51 was negative in all 11 patients and we did not find any significant accumulation of other HLA-subgroups. Our study does not support an association between susceptibility to stroke after varicella and HLA-B51. PMID- 11764185 TI - Extra-pyramidal parkinsonism complicating organophosphate insecticide poisoning. AB - We present a 1 7-year-old female with acute extra-pyramidal parkinsonism complicating a suicidal attempt with the organophosphate insecticide chlorpyrifos, who was initially suspected to have developed severe depression or psychosis. On admission she was stupurous, with diarrhoea and massive salivation lapsing into respiratory failure and coma. Following atropine and toxogonin treatment along with mechanical ventilation she developed overt extrapyramidal parkinsonism and encephalopathy, characterized by impaired sensorium and agitation, mask facies along with a muffled voice and swallowing impairment, a resting tremor with cogwheel rigidity switching to bradykinetic choreoathetotic movements. Once a parkinsonian syndrome was diagnosed, she was given amantadine therapy with complete recovery. The patient is presently maintained on amantadine therapy; there was mild worsening of her extrapyramidal signs following unplanned discontinuation of this medication, and on follow-up assessments after 9 months she is virtually asymptomatic. A parkinsonian extrapyramidal syndrome, complicating organophosphate intoxication, should therefore also be taken into account in any patient with organophosphate poisoning, presenting with marked behavioural alterations, rigidity or akinetic mutism, and beneficial response to amantadine. PMID- 11764186 TI - Paediatric and adult movement disorders (update). PMID- 11764187 TI - Effects of different probiotic strains of Lactobacillus and Bifidobacterium on bacterial translocation and liver injury in an acute liver injury model. AB - Septic complications represent frequent causes of morbidity in liver diseases and following hepatic operations. Most infections are caused by the individual own intestinal microflora. The intestinal microflora composition is important in physiological and pathophysiological processes in the human gastrointestinal tract, but their influence on liver in different situations is unclear. We therefore studied the effect of different Lactobacillus strains and a Bifidobacterium strain on the extent of liver injury, bacterial translocation and intestinal microflora in an acute liver injury model. Sprague-Dawley rats were divided into five groups: acute liver injury control, acute liver injury + B. animalis NM2, acute liver injury + L. acidophilus NMI, acute liver injury + L. rhamnosus ATCC 53103, and acute liver injury + L. rhamnosus DSM 6594 and L. plantarum DSM 9843. The bacteria were administered rectally daily for 8 days. Liver injury was induced on the 8th day by intraperitoneal injection of D galactosamine (1.1 g/kg BW). Samples were collected 24 h after the liver injury. Liver enzymes and bilirubin serum levels, bacterial translocation (to arterial and portal blood, liver and mesenteric lymph nodes (MLNs)), and intestinal microflora were evaluated. L. acidophilus NM1; L. rhamnosus ATCC 53103, and L. rhamnosus DSM 6594 + L. plantarum DSM 9843 decreased bacterial translocation compared to the liver injury control group. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes. The levels of alanine aminotransferase (ALAT) were significantly lower in the L. acidophilus, L. rhamnosus ATCC 53103, L. rhamnosus DSM 6594 + L. plantarum DSM 9843 groups compared to the liver injury group. The L. rhamnosus and L. rhamnosus + L. plantarum groups significantly reduced ALAT levels compared to the B. animalis group. All administered bacteria decreased the Enterobacteriaceae count in the cecum and colon. Administration of different lactobacilli and a Bifidobacterium strain in an acute liver injury rat model, has shown different effects on bacterial translocation and hepatocellular damage. L. acidophilus, L. rhamnosus, and L. rhamnosus + L. plantarum reduced bacterial translocation and hepatocellular damage. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes and did not affect hepatocellular damage. PMID- 11764188 TI - Microbiological quality and shelf-life of vacuum-packaged 'gravad' rainbow trout stored at 3 and 8 degrees C. AB - Microbiological and sensory changes of vacuum-packaged 'gravad' rainbow trout slices were studied during storage at 3 and 8 degrees C. At the time of spoilage, after 27 and 20 days of storage at 3 and 8 degrees C, respectively, both mesophilic viable counts (MVC) and psychrotrophic viable counts (PVC) reached 10(6)-10(7) cfu/g at 3 degrees C and 10(7)-10(5) cfu/g at 8 degrees C. H2S producing bacteria constituted a high proportion of the PVCs and lactic acid bacteria (LAB) counts were lower than the other determined bacterial counts. Sensory scores decreased with increasing MVC and PVC. The judges considered samples unfit for human consumption at MVC and PVC levels exceeding 10(6) and 10(7) cfu/g for samples stored at 3 and 8 degrees C, respectively. At respective levels of 10(7) and 10(8) cfu/g, most of the samples were deemed unfit. The main reasons for sensory rejection at both storage temperatures were the lack of the typical product odour or an ammonia off-odour and colour change to dark violet. The shelf-lives of the rainbow trout slices based on microbiological and sensory analyses were 20 days and 18 days at 3 and 8 degrees C, respectively. PMID- 11764189 TI - Salmonella in slaughter pigs: the effect of logistic slaughter procedures of pigs on the prevalence of Salmonella in pork. AB - A substantial part of the finishing pigs in the Netherlands is infected with Salmonella. Infection of pigs with Salmonella can occur already on the farm. Pigs can also get infected or contaminated during transport, lairage or slaughter. The aim of this study was to evaluate the effect of separating pigs from Salmonella infected farms from pigs from Salmonella-free farms during transport, lairage and slaughter on the prevalence of Salmonella on pork after slaughter. Two experiments were carried out. In the first experiment, farms were selected to participate, based on serology of the pigs (Dutch Salmonella ELISA). The pigs were slaughtered at the beginning of the day: firstly, sero-negative herds, secondly, sero-positive herds and thirdly, again sero-negative herds. The latter were slaughtered to investigate the effect of a contaminated slaughterline due to a previously slaughtered positive herd. In the second experiment, farms were selected to participate, based on both serology and bacteriology of the pigs on the farm. Two hundred pigs from Salmonella-free farms were slaughtered after 200 pigs from Salmonella-infected farms. Results showed that the prevalence of Salmonella in pork samples of sero-negative herds was lower than in samples of sero-positive herds. Results also showed that Salmonella contamination of carcasses after slaughter was partially caused by Salmonella-infected herds that were slaughtered before, and partially by residential flora of the slaughterhouse. It is concluded that separate slaughter of sero-negative pig herds can be useful to decrease the prevalence of Salmonella-contaminated pork after slaughter. To avoid cross-contamination by residential flora from trucks, lairage and slaughterline, cleaning and disinfection have to be improved. PMID- 11764190 TI - Salmonella in slaughter pigs: prevalence, serotypes and critical control points during slaughter in two slaughterhouses. AB - The purpose of this study was to show the distribution of Salmonella in slaughtered pigs and the environment of the slaughterhouse. 1,114 samples of slaughtered pigs (six different samples for Salmonella isolation and one serum sample for ELISA on antibodies per pig) and 477 samples of the slaughterhouse environment were collected in two slaughterhouses on two sampling days per slaughterhouse. Salmonella was isolated from one or more samples of 47% of the pigs. The highest prevalence of Salmonella was observed in rectal content samples (25.6%), whereas the lowest prevalence of Salmonella was observed on the carcasses (1.4%). The prevalence of Salmonella in other samples was: 19.6% in tonsils, 9.3% on livers, 9.3% on tongues, and 9.3% in mesenterial lymphnodes. The prevalence of Salmonella in environmental samples was high in the drain water samples in both slaughterhouses (61%) and on the carcass splitter in one slaughterhouse (33%). Salmonella typhimurium was the most frequently isolated serotype in pig samples and environmental samples in both slaughterhouses: 43% of the Salmonella isolates from pigs and 33% of the Salmonella isolates from the environment was S. typhimurium. The results of this study show that Salmonella prevalences in pigs differ a lot, depending on which part of the pig is sampled. Not all different samples of the pig will become available for human consumption, but collecting more than one sample per pig showed that Salmonella can be found in almost the whole pig. The result of surface samples of carcass and liver gives information about hygiene during the slaughter process; the result of tonsils, lymphnodes and rectal contents, combined with the serological result, gives information about infection of the pig before the slaughter process (on the farm, during transport or in lairage). It can be concluded that results of Salmonella isolation of slaughter pigs should always be carefully interpreted, depending on the type of sample that has been collected. PMID- 11764191 TI - Evaluation of culture media for enrichment and isolation of Shigella sonnei and S. flexneri. AB - The performance of Gram-negative (GN) broth with (10 microg/ml) and without novobiocin, Shigella broth (SB) with 0.5 and 3.0 microg/ml novobiocin, all incubated at 37 degrees C (SB with 3.0 microg/ml novobiocin also at 42 degrees C) and buffered brilliant green bile glucose (EE) broth with 1.0 microg/ml novobiocin incubated at 37 and 42 degrees C were evaluated for resuscitation and growth of Shigella sonnei and S. flexneri (eight strains; unstressed, chill stressed and acid-stressed) and non-shigellae (11 strains). GN broth with or without novobiocin supported significantly less growth of Shigella sp. No significant differences in growth of shigellae were obtained between the other culture media. Performance depended more on the Shigella strain used. None of the tested media were significantly superior for suppressing the competitive flora. Electivity and selectivity of MacConkey agar (MAC), tergitol-7 agar (T7), desoxycholate citrate agar (DCA), xylose lysine desoxycholate agar (XLD), Salmonella Shigella agar and Hektoen enteric agar (HEA) were determined by ecometric testing. HEA confirmed to be a high selective medium for both non shigellae and stressed Shigella sp. Klebsiella sp., Enterobacter sp., Citrobacter sp.. Salmonella sp. and the Escherichia strains can mask the presence of shigellae. In vitro competition experiments and experiments with artificially contaminated foods showed higher resistance of S. sonnei than S. flexneri towards the stress imposed by the food matrix and its indigenous flora. Reliable detection, however, of shigellae in foods with the current enrichment and isolation media was not achieved. PMID- 11764192 TI - Nutritional factors affecting the production of two bacteriocins from lactic acid bacteria on whey. AB - The ability of Lactococcus lactis subsp. lactis CECT 539 and Pediococcus acidilactici NRRL B-5627 to produce bacteriocins on both diluted and concentrated whey was investigated in batch fermentations. Both strains produced the higher amounts of biomass and bacteriocin titres on diluted whey. Luedeking and Piret expression was able to model the production of nisin, which was produced as a primary metabolite on both culture media. However, the pediocin production could not be typified in any case due to the negligible growth of P. acidilactici. Although the whey supported the growth and bacteriocin production by the two strains, both biomass and bacteriocin productions were lower than those obtained on MRS broth. The effect of total sugar, nitrogen, phosphorous and buffer concentrations on the production of nisin and pediocin was studied in diluted whey using factorial experiments and empirical modelling. The production of nisin was greatly inhibited by the increase in nitrogen, buffer, and to a lesser extent, sugar concentration in the medium, nevertheless, the used phosphorous source produced a light stimulatory effect on bacteriocin synthesis. In addition, the growth of Lc 1.04 was mainly affected by the nitrogen source used. On the other hand, pediocin was inhibited by the increase in buffer, phosphorous, and to a lesser degree, by the sugar and nitrogen concentration. The inhibitory activity of pediocin disappeared almost totally after 15 min of treatment with trypsin, papain, subtilisin and pepsin. The activity of nisin was drastically reduced by treatment with trypsin, subtilisin and pepsin. Nevertheless, 50% of the initial activity was retained when nisin was treated with papain. Both bacteriocins showed the highest heat stability at acidic pH and short incubation times. PMID- 11764193 TI - Studies on acetate ester production by non-saccharomyces wine yeasts. AB - A double coupling bioreactor system was used to fast screen yeast strains for the production of acetate esters. Eleven yeast strains were used belonging to the genera Candida, Hanseniaspora, Metschnikowia, Pichia, Schizosaccharomyces and Zygosacharomyces, mainly isolated from grapes and wine, and two wine Saccharomyces cerevisiae strains. The acetate ester forming activities of yeast strains belonging to the genera Hanseniaspora (Hanseniaspora guilliermondii and H. uvarum) and Pichia (Pichia anomala) showed different substrate specificities and were able to produce ethyl acetate, geranyl acetate, isoamyl acetate and 2 phenylethyl acetate. The influence of aeration culture conditions on the formation of acetate esters by non-Saccharomyces wine yeast and S. cerevisiae was examined by growing the yeasts on synthetic microbiological medium. S. cerevisiae produced low levels of acetate esters when the cells were cultured under highly aeration conditions, while, under the same conditions, H. guilliermondii 11104 and P. anomala 10590 were found to be strong producers of 2-phenylethyl acetate and isoamyl acetate, respectively. PMID- 11764194 TI - Biochemical and genetic evidence for production of enterocins A and B by Enterococcus faecium WHE 81. AB - Enterococcus faecium WHE 81, isolated from cheese, has been reported to produce a bacteriocin called "enterocin 81" [J. Appl. Microbiol. 85 (1998) 521.]. Purification of "enterocin 81" was carried out using ammonium sulfate precipitation, desalting on ODP-90 reverse-phase column, and purification through SP Sepharose HP cation exchange and C2/C18 reverse-phase chromatographies. The antimicrobial was eluted from the C2/C18 column as four individually active fractions, designated A81, B81, C81 and D81. The purification procedure used proved particularly efficient for the bacteriocin in fraction D81, with a yield of 46%, while only 3.8% the bacteriocin in fraction B81 could be collected. MALDI TOF mass spectrometry of the bacteriocins in fractions B81 and D81 showed respective masses of 4,833.0 and 5,462.2 Da. Amino acid sequencing of the two peptides revealed two class-II bacteriocins whose sequences were similar to those of enterocin A and enterocin B, respectively. Using proper primers, chromosomal fragments of 212 and 216 bp enclosing bacteriocin structural genes were PCR amplified. Cloning of the amplicons and their sequencing revealed two genes with sequences identical to the structural genes of enterocins A and B, respectively. It was therefore clearly established that E. faecium WHE 81 produces bacteriocins respectively identical to enterocins A and B. Our results, combined with data from previous reports, suggest that the two bacteriocins may be widespread among enterococcal strains and may play an important role in controlling the growth of pathogens and other undesirable bacteria in certain fermented food products. PMID- 11764195 TI - The peptide hydrolase system of Lactobacillus reuteri. AB - Peptide hydrolase system of Lactobacillus reuteri CRL 1098, a lactic acid bacteria of sourdough origin, was investigated. This microorganism has a broad range of peptidases consisting of an active aminopeptidase, X-Prolyl dipeptidylaminopeptidase, dipeptidase and tripeptidase. Aminopeptidase, iminopeptidase and endopeptidase are most likely located in the cytoplasmic fraction showing no detectable association with the cell membrane, while dipeptidase and tripeptidase are mainly associated with the latter fraction. The peptidases are metalloenzymes activated by Co2+ and inhibited by Cu2+, Hg2+, Cd2+ and by metal-complexing reagents. The aminopeptidase activity inhibited by EDTA can be restored by Mn2+ while that of di- and tripeptidase treated with 1,10 phenantroline can be restored by Zn2+ and Co2+, respectively. PMID- 11764196 TI - Bibliography of food microbiology. PMID- 11764197 TI - Should you be reading this journal? PMID- 11764198 TI - Rheumatoid arthritis, methotrexate, and lymphoma: risk substitution, or cat and mouse with Epstein-Barr virus? PMID- 11764199 TI - Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis. AB - OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA. PMID- 11764200 TI - Expression of CD44 in synovium of rabbits with chronic arthritis induced by immunization with Escherichia coli. AB - OBJECTIVE: To investigate the expression of CD44 and its role in experimental chronic arthritis in rabbits. METHODS: Rabbits were immunized with Escherichia coli 0:14 for short (4 mo) and long (8-10 mo) periods. Immunohistochemical staining was performed on knees, using anti-CD44 antibodies. RESULTS: Lymphocyte infiltration in the synovium was found in 30.0% of rabbits after short term immunization, and the rate increased to 58.3% after longterm immunization. CD44 was present in synovial lining cells in 30.0% of rabbits after short term immunization, and it increased significantly (p < 0.05) after longterm immunization (66.7%). CD44 was also observed in lymphocytes in knee synovium after longterm immunization (25.0%). CONCLUSION: CD44 in lining cells might play a role in promoting chronic arthritis in rabbits immunized with E. coli. PMID- 11764201 TI - Soluble CD154 in rheumatoid arthritis: elevated plasma levels in cases with vasculitis. AB - OBJECTIVE: To determine the levels of soluble CD154 (sCD154) in the plasma of patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV). and to examine the relationship between the levels of sCD154 in plasma and the clinical variables. METHODS: Levels of sCD154 were quantified in 39 plasma samples from patients with RA, including 9 patients who were also diagnosed with RV, and compared with those of 20 healthy subjects. An ELISA was established and specificity of the ELISA was tested by control ELISA using isotype-matched IgG and preabsorption assay. The titers of IgM and IgG rheumatoid factor (IgM-RF, IgG RF) for each patient were determined simultaneously, and values of other laboratory variables were also determined. RESULTS: Levels of sCD 154 in plasma were higher in patients with RA than in the healthy subjects (p < 0.02). Compared with RA patients without vasculitis, patients with RV had significantly higher levels of sCD154 in their plasma (p < 0.001). Control ELISA and absorption assay of sCD154 indicated that our ELISA system was capable of measuring plasma sCD154 in RA patients. Levels of sCD154 in RA plasma correlated significantly with both IgM-RF and IgG-RF titers (r = 0.64 and 0.61, respectively, both p < 0.001). The levels of sCD154 decreased after commencement of treatment for vasculitis in cases with RV. CONCLUSION: We identified the presence of sCD154 in RA plasma, with especially high levels in cases with vasculitis. Correlation between sCD154 and RF titers indicates the CD154-CD40 pathway is likely related to pathogenic RF production. PMID- 11764202 TI - Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells. AB - OBJECTIVE: To investigate the mechanism of the immunosuppressive effect of T-614 [N-(3-formylamino-4-oxo-6-phenoxy-4H-chromen-7-yl)methanesulfonamide], a new antirheumatic drug whose clinical efficacy has been determined for the treatment of patients with rheumatoid arthritis (RA). METHODS: RA synovial fibroblast-like cells were cultured with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) in the presence or absence of T-614. After incubation, cytokine production was measured by ELISA. Expression of interleukin 6 (IL-6) and IL-8 mRNA was examined by real time quantitative reverse transcriptase-polymerase chain reaction analysis and TNF-alpha induced nuclear factor-kappaB (NF-kappaB) activation was observed using immunostaining with an antibody against NF-kappaB p65. RESULTS: T-614 suppressed TNF-alpha induced production of IL-6, IL-8, and monocyte chemoattractant protein 1, and also reduced the accumulation of IL-6 and IL-8 mRNA in a concentration dependent manner. T-614 interfered with the TNF-alpha induced translocation of NF kappaB to the nucleus from the cytoplasm. CONCLUSION: Inhibition of NF-kappaB activation and transcription of proinflammatory cytokines by T-614 contributes to its clinical antirheumatic effect. PMID- 11764203 TI - Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. AB - OBJECTIVE: To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. METHODS: Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE selectin). RESULTS: Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. CONCLUSION: Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels. PMID- 11764204 TI - Ability of hand radiographs to predict a further diagnosis of rheumatoid arthritis in patients with early arthritis. AB - OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well. PMID- 11764205 TI - Identification of radiologic healing phenomena in patients with rheumatoid arthritis. AB - OBJECTIVE: Conventional radiographic scoring methods in rheumatoid arthritis (RA) are designed to quantify progression and disregard any improvement. Reparative changes observed during longterm followup of RA have rarely been described as healing phenomena. Healing may become increasingly important with the availability of more potent antirheumatic drugs. We investigated whether radiologic healing phenomena can be identified by different observers in a blinded fashion. METHODS: Healing phenomena were defined as (1) reappearance (and sclerosis) of the cortical plate, (2) partial or complete filling in of an erosion, or (3) subchondral bone sclerosis with osteophyte formation (secondary osteoarthritis). Pairs of radiographs of hands, wrists, and forefeet [taken 2 to 8 (mean 4.8) yrs apart] of 34 patients were selected from longterm studies: 24 sets with healing phenomena and 10 with progressive disease without healing. The radiographs were blinded and read in pairs in random order by 3 observers unaware of the patients selected for the study. One observer read the set a second time after 8 weeks, resulting in a total of 4 observations. Thirty-eight joints were rated 0 to 5 depending on the amount of surface destruction. In addition an attempt was made to identify joints with healing phenomena. The data were analyzed with help of descriptive statistics such as means, standard deviations, and frequency tables. RESULTS: Out of 1292 joints scored at the second time point, 74 had healing phenomena. These joints were identified in a mean of 89% (95/89/88/82%, respectively) in the 4 observations performed by the 3 readers. Patients without healing phenomena were correctly identified by all observers. In 54 joints less typical healing phenomena were seen in all observations. Sixty-two joints with healing in addition to the 74 joints were seen in 3 observations, 76 in 2, and 127 in one observation. All observers agreed that 1090 joints had no healing phenomenon. The 24 patients with healing had a slight reduction in the Ratingen score, while the 10 patients without healing showed a moderate progression. In the group with healing an increase and decrease in the score occurred in the same patients at different joints. CONCLUSION: In patients with RA followed for several years healing or reparative changes of erosions can be observed. These phenomena can be identified by different observers with high sensitivity even when the observers are blinded to chronological sequence of the films. PMID- 11764206 TI - Comparative responsiveness of four elbow scoring instruments in patients with rheumatoid arthritis. AB - OBJECTIVE: This prospective study investigated the comparative responsiveness to change of 4 different elbow scoring instruments: 2 Hospital for Special Surgery elbow assessment scales, the Mayo Clinic Elbow Performance Index, and the Elbow Functional Assessment (EFA) Scale. METHODS: A group of patients with rheumatoid arthritis (RA) (median age 60 yrs) undergoing either elbow arthroplasty (22 elbows) or synovectomy with radial head excision (3 elbows) were evaluated both before and after surgery (median 7 mo postoperatively). Changes in the scores obtained using the scales under study were calculated and analyzed. The patient's opinion of global perceived effect of the intervention was used as an external criterion to classify them as "improved" or "non-changed." Responsiveness was evaluated with 3 different statistical approaches: using paired t statistics (pre and postsurgery scores), effect size statistics (standardized response mean, effect size, and responsiveness ratios), and receiver operator characteristic curves. Minimal clinically important difference was estimated using patient satisfaction as the external criterion. RESULTS: Each of the elbow rating measures under study proved to be responsive to change when evaluating patients with RA undergoing elbow arthroplasty or synovectomy. The EFA scale had the highest power to detect a clinically meaningful difference and had the best discriminative ability to distinguish improved from no-change patients, as shown by all responsiveness statistics applied. CONCLUSION: Using the EFA scale requires smaller sample sizes to achieve a fixed level of statistical power than the other scales we studied. PMID- 11764207 TI - Disturbed grip function in women with rheumatoid arthritis. AB - OBJECTIVE: Hand dysfunction is a frequent cause of disability in rheumatoid arthritis (RA). In patients with RA, we studied the precision grip-lift sequence in relation to pain, stiffness, and observer assessed hand function and their relation to patients' experience of clumsiness and tendency to drop objects. METHODS: Performance of the precision grip-lift sequence was studied in 23 women with RA and 7 age and sex matched controls. The results were correlated to self estimation of pain and stiffness of hands and to observer assessed measurements of hand function. RESULTS: A prolongation of the preload and loading phases and of the acceleration part of the transition phase as well as a disturbance of the safety margin (SM) during precision grip-lift were noted. Patients with good hand function (low Grip Ability Test score; GAT) displayed normal or increased SM compared to the healthy controls, whereas patients with more pronounced disease exhibited a lower SM. Disturbances seen in the precision grip-lift performance were related to stiffness, range of motion, and GAT score. In RA patients with decreased hand function the SM was correlated to feeling of clumsiness, but did not explain the frequency of object dropping. CONCLUSION: A disturbance in the precision grip-lift performance was noted in patients with RA. These grip performance changes need further investigation to determine possible mechanisms. PMID- 11764208 TI - Effects of pulse methylprednisolone on macrophage chemotactic protein-1 and macrophage inflammatory protein-1alpha in rheumatoid synovium. AB - OBJECTIVE: To determine the effect of pulse methyprednisolone (PMP; 1000 mg) on the expression of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha in rheumatoid synovial membrane. METHODS: Seven patients with rheumatoid arthritis (RA) were studied. Arthroscopically-directed synovial biopsies were taken before and 24 hours after treatment with intravenous PMP. Synovial membranes were stained by immunohistochemical techniques with monoclonal antibodies against MCP-1, MIP-1alpha and CD68 (a macrophage marker). Quantitation of staining was performed by computer-assisted color video image analysis. RESULTS: PMP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of MCP-1 and MIP-1alpha expression by a mean of 55% (p = 0.05) and 45% (p = 0.03), respectively, with no effect on CD68 expression in the synovial lining layer. There was no significant change in MCP 1, MIP-1alpha or CD68 expression in the synovial sublining. CONCLUSION: PMP therapy rapidly reduces MCP-1 and MIP-1alpha levels in the synovial lining layer without a fall in macrophage numbers. It thus appears that the initial effect of PMP is that of reducing macrophage activation. PMID- 11764209 TI - The value of IgA antiphospholipid testing for diagnosis of antiphospholipid (Hughes) syndrome in systemic lupus erythematosus. AB - OBJECTIVE: It is recognized that the presence of IgG and IgM anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) is associated with thrombosis in patients with antiphospholipid syndrome (APS). Some reports have shown that testing for IgA anticardiolipin and anti-beta2-glycoprotein antibodies (anti beta2-GPI) provides extra diagnostic help in patients with APS, while other authors could not support this data. We designed this cross sectional study to determine the prevalence of IgA aCL, anti-beta2-GPI, and antiprothrombin antibodies and to study their clinical significance in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: This study comprised 134 SLE patients (126 women; median age 37.5 yrs, range 16-72). The median duration of the disease was 9 years, range 0.1-38. Of these, 55 (41%) had a history of thrombotic events: 22 (40%) presented an arterial event, 22 (40%) a venous event, and 11 (20%) both arterial and venous events. Of 49 women who had been pregnant, 18 (37%) gave a history of recurrent pregnancy loss. Thrombocytopenia was present in 14/127 patients (11%). Forty patients (30%) were diagnosed as APS secondary to SLE, 23 (17%) had IgG/M aCL and/or LAC without clinical features of APS, and 71 (53%) were SLE patients who were repeatedly negative for IgG/M aCL or LAC. IgG, IgM, IgA aCL and anti-beta2-GPI were detected by ELISA. Antibodies directed to prothrombin were detected by 2 ELISA using prothrombin coated on irradiated plates (aPT) and phosphatidylserine/prothrombin complex (aPS/PT) as antigen. RESULTS: IgA aCL were found in 18/134 (13%) patients. Of these, 3 (17%) had IgA aCL as well as IgG/M aCL, and 2 (11%) had IgG/M aCL and anti-beta2-GPI. Of the 18 patients positive for IgA aCL, 8 were also positive for LAC. Of these, one (5%) patient had IgA aCL as well as other isotype of aCL, and 7 (39%) patients had both aCL and anti-beta2-GPI. None of these patients had binding of IgA aPT or aPS/PT. Of the entire group of 18 patients, 5 (28%) had IgA aCL as the sole aPL. Four of 5 of these patients were diagnosed as SLE but had no antiphospholipid (aPL) related clinical manifestations. We found no association between the presence of IgA aCL and clinical manifestations of APS. IgA anti-beta2-GPI were found in 8/134 (6%) patients. Of these, one (12.5%) had IgA anti-beta2-GPI as well as IgG/M anti-beta2-GPI and aCL. Of the 8 patients positive for IgA anti beta2-GPI, 6 (75%) were also positive for LAC. Of these, one (12.5%) patient presented with IgA anti-beta2-GPI along with other isotypes of aCL, and 4 (50%) patients with aCL and other isotype of anti-beta2-GPI. One patient (12.5%) had IgA anti-beta2-GPI along with LAC only, and one patient (12.5%) who was diagnosed as SLE had no aPL related clinical manifestation but had IgA anti-beta2-GPI as the sole aPL. CONCLUSION: IgA aCL and anti-beta2-GPI are found in SLE, usually along with IgG and/or IgM isotypes. Testing for IgA aCL and anti-beta2-GPI is not a helpful screening test and does not contribute to the recognition of APS in SLE. IgA aPT and aPS/PT are not present in patients with SLE, therefore there is no need to test for these antibodies. PMID- 11764210 TI - Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. AB - OBJECTIVE: To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls. METHODS: T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2 fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR. RESULTS: Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA. CONCLUSION: These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE. PMID- 11764211 TI - Association of the A561C E-selectin polymorphism with systemic lupus erythematosus in 2 independent populations. AB - OBJECTIVE: E-selectin is expressed on cytokine stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. The gene for E-selectin is located at chromosome 1q 23-25 within the linkage area for systemic lupus erythematosus (SLE). The best characterized polymorphism in E-selectin molecule is A561C, which codes for Ser128Arg. We studied the prevalence of the A561C E-selectin gene polymorphism in patients with SLE and controls from 3 different ethnic populations. METHODS: Three cohorts of patients with SLE (1987 American College of Rheumatology criteria) and matching population controls were studied. These consisted of Caucasians of British Isles descent, Caucasians of Spanish origin, and Caucasians of Turkish origin. We used polymerase chain reaction and restriction fragment length polymorphism to genotype patients and controls. RESULTS: The numbers of patients and controls in each group were: UK (113 and 148), Spanish (145 and 179), and Turkish (93 and 96), respectively. The C allele occurred more frequently in UK and Spanish patients (OR 1.76, 95% CI 1.03-3.0, p = 0.037; and OR 1.84, 95% CI 1.1-3.09, p = 0.019), but not in Turkish patients (OR 1.03, 95% CI 0.55-1.97, p = 0.91). CONCLUSION: In 2 of 3 populations studied, the E selectin C allele was significantly more common in SLE than in controls. E selectin may be a susceptibility gene to SLE in these populations. Its role in disease expression and longterm outcomes such as accelerated atherosclerosis requires further study. PMID- 11764212 TI - Smoking and use of hair treatments in relation to risk of developing systemic lupus erythematosus. AB - OBJECTIVE: To examine the association between smoking and hair treatments (dyes, permanents) and risk of developing systemic lupus erythematosus (SLE). METHODS: Patients (n = 265) diagnosed between January 1, 1995, and July 31, 1999, were recruited through 4 university based and 30 community based rheumatology practices in eastern North Carolina and South Carolina. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included a 60 min in-person interview. Analyses were limited to experiences that occurred before age at diagnosis (patients) or reference age (controls). Because the prevalence of use of hair treatments among men was very low, the analyses of those exposures were limited to women. RESULTS: There was no association with smoking history and risk of developing SLE when analyzed as status (current, former, or never-smoker) or measures of dose (duration or pack-years). Use of permanent hair dyes in women was associated with a small increased risk of developing SLE (OR 1.5, 95% CI 1.0, 2.2). This association increased with longer duration of use (compared with nonusers, OR 1.7, 95% CI 1.0, 2.7 for 6 or more years). There was little evidence of an association between SLE and use of temporary dyes or of permanents and straighteners. CONCLUSION: These results suggest at most a weak association between SLE risk and permanent hair dyes or smoking. Genetic variability in the metabolism of these products may be important to assess in future studies. PMID- 11764213 TI - Widespread pain and Sjogren's syndrome. AB - OBJECTIVE: Reports exist of an association between fibromyalgia (FM) and Sjogren's syndrome (SS). Widespread pain is a necessary component of FM. We explored the association of widespread pain and SS. METHODS: Data were abstracted from the records of the most recent 100 patients evaluated in the SS clinic. The subjects included individuals with or without SS who had screened for features of the disorder. Patients with confounding disorders or missing data were excluded. The presence of widespread pain was established by questionnaire in 92 subjects. Widespread pain followed the definition in the 1990 American College of Rheumatology classification criteria for FM. By objective criteria used in the clinic, patients were initially classified into SS (requiring keratoconjunctivitis sicca. positive labial salivary gland biopsy, and serological evidence of autoimmunity), incomplete SS (at least one of the latter objective findings), or non-SS (if all 3 objective findings were negative). For subsequent analyses, the study population was also classified into cases by applying the European criteria for SS, and the subjective or objective components of European criteria. Descriptive statistics and Cochran-Mantel chi-square tests were performed. RESULTS: Only 2/27 (7%) of those diagnosed with SS reported symptoms of widespread pain. The incomplete SS group consisted of 8/56 (14%), while the non-SS were 1/9 (11%). There was a trend toward greater widespread pain in those 9 of 52 (17%) subjects meeting the European criteria for SS who had widespread pain compared with 2 of 50 (5%) who did not. However, this was not significant (p = 0.0728). The greater the subjectivity of the criteria applied to classify cases of SS, the higher was the prevalence of widespread pain. No significant association was found between widespread pain and SS for any of the criteria applied. CONCLUSION: No significant association between widespread pain and SS was found in our study population. Further study is indicated to explore a possible lack of association between SS and FM. PMID- 11764214 TI - HLA-DRB1 associations in biopsy proven erythema nodosum. AB - OBJECTIVE: To examine the HLA-DRB1 associations of patients with erythema nodosum (EN), establish HLA-DRB1 differences among patients with idiopathic and secondary EN, and identify the HLA-DRB1 associations with specific conditions presenting with EN. METHODS: We conducted a retrospective study of 100 patients (83 women) with biopsy proven EN diagnosed for a defined population in Northwest Spain. Patients were classified into idiopathic or secondary if skin nodules occurred in the context of a well defined disease, or there was a precipitating event in close temporal relationship with the onset of EN. Patients and controls were HLA DRB1 genotyped from DNA using molecular based methods. RESULTS: At the time of diagnosis no precipitating events or underlying diseases were identified in 35 cases and, due to this, they were considered to be idiopathic. Although strong associations do not appear to exist between HLA-DRB1 and unstratified EN, the idiopathic group showed a significantly lower frequency of HLA-DRB1*04 phenotype compared with controls. Among the patients with secondary EN, the patient subgroup with sarcoidosis exhibited a significantly increased frequency of HLA DRB1* 13 compared with healthy controls. CONCLUSION: Idiopathic and some groups of secondary EN seem to have different HLA-DRB1 associations. These differences may have prognostic value in identifying patients with specific conditions associated with this syndrome. PMID- 11764215 TI - Acetabular osteitis in ankylosing spondylitis: does fibrillin figure in its pathogenesis? AB - In the hip and sacroiliac joints, ankylosing spondylitis attacks the acetabulum over the femoral head and the ilium in preference to the sacrum. Both sites involve inflammation in bone subjacent to fibrocartilage with relative sparing of opposing, hyaline cartilage-surfaced mates. This disease appears to target connective tissues rich in fibrillin-1. A cell-mediated autoimmune response may be involved. PMID- 11764216 TI - Inflammatory eye, skin, and bowel disease in spondyloarthritis: genetic, phenotypic, and environmental factors. AB - OBJECTIVE: To explore the nature of the interrelationship between inflammatory disease of the spine/joints, skin, eye, and bowel [i.e., ankylosing spondylitis (AS), psoriasis, iritis, inflammatory bowel disease (IBD)]. METHODS: The study used 4 approaches: (1) analysis of the prevalence of secondary disorders within the AS individual (chi-square and matched pair analysis); (2) study of the temporal relationship between the onset of the different conditions; (3) evaluation of the prevalence of disease among first degree relatives; and (4) influence of secondary disorders on outcome of AS. RESULTS: 1. Among 3287 patients with AS, more than expected had either spondylitis associated with multiple co-disorders or pure AS (with no co-diseases); fewer than expected had AS plus a single co-disease (chi-square = 32.2, p < 0.001). In a matched pair analysis, patients with AS and a secondary disorder were more likely to have an additional concomitant disease, e.g., IBD-AS (n = 335) patients had a higher prevalence of iritis [45.4% vs 36.7%; OR 1.4 (1.1-2.0)] or psoriasis [23.9% vs 14.3%; OR 1.9 (1.3-2.8)] than controls. 2. Among our database subjects, the symptomatic onset of the spinal disease precedes or is contemporaneous with gut, skin, and eye involvement (matched pair t test, p < 0.001). 3. Patients with multiple disorders predict the highest prevalence of co-diseases (i.e., psoriasis, IBD, iritis, or AS) within family members, followed by those AS patients with only IBD, psoriasis, or iritis in descending order. 4. Both psoriasis and IBD increase severity in terrms of function and disease activity of AS in the patient. Radiological change is greatest for those AS subjects with iritis. CONCLUSION: There is a striking overlap within patients and family members of rheumatological, dermatological, and gastroenterological diseases. The susceptibility genes of these co-disorders appear to overlap with each other and with AS: 1. A patient with 2 inflammatory conditions is at an increased risk of developing an additional related inflammatory disorder. 2. Those with enteropathic spondylarthritis would appear to carry the greatest genetic load in terms of first degree relatives developing inflammatory conditions (including psoriasis and iritis that are not seen in the index IBD-AS patient). 3. The secondary disorders do not precede AS (arguing against psoriasis and IBD allowing for an environmental conduit to pathogenic triggers in AS). The susceptibility factors for these inflammatory conditions may be additive or have a synergistic effect on each other. There is evidence for a shared gene hypothesis. PMID- 11764217 TI - Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals. AB - OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique. RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen. CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals. PMID- 11764218 TI - The nucleoside triphosphate pyrophosphohydrolase isozyme PC-1 directly promotes cartilage calcification through chondrocyte apoptosis and increased calcium precipitation by mineralizing vesicles. AB - OBJECTIVE: Aging associated elevations of cartilage extracellular inorganic pyrophosphate (PPi) and PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) are linked with degenerative arthritis in chondrocalcinosis. Increased chondrocyte apoptosis and expression of annexin V occur at sites of matrix calcification in degenerative arthritis, and membrane limited chondrocyte apoptotic bodies containing NTPPPH may promote chondrocalcinosis by acting as mineralizing matrix vesicles (MV). Because chondrocytes express 3 related NTPPPH isozymes [PC-1, autotaxin (ATX), and B10/PDNP3], we evaluated the effects on apoptosis and MV mediated calcium precipitation of direct expression of NTPPPH isozymes. METHODS: To achieve "gain of function" of NTPPPH isozymes, we expressed the isozymes in cultured chondrocytic cells. RESULTS: Plasmid cDNA transfection of PC-1, but not ATX or B10/PDNP3, markedly increased apoptosis of cultured chondrocytic knee meniscal cells and increased calcium precipitation by MV fractions. The capacity of PC-1 to increase chondrocyte and meniscal cell apoptosis, and calcium precipitation by MV, further analyzed using adenoviral gene transfer in cultured meniscal cells and articular chondrocytes, was shown to be dependent on integrity of the PC-I NTPPPH catalytic site. The MV-containing fraction released from meniscal cells and chondrocytes that overexpressed wild-type PC-1 had increased annexin V. Use of antibodies to annexin V and PC-1 revealed that both annexin V and PC-1 directly mediated the elevated calcium-precipitating capacity of MV. The increased ability of MV to precipitate calcium from PC-1-overexpressing cells did not require exogenous ATP. CONCLUSION: Upregulated expression of enzymatically active PC-1 directly promotes apoptosis, increased MV annexin V, and an increased capacity of meniscal cell and articular chondrocyte MV to precipitate calcium. These results suggest a direct link between increased PC-1 expression and the pathogenesis of chondrocalcinosis. PMID- 11764219 TI - Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes. AB - OBJECTIVE: Interleukin 1 receptor antagonist (IL-1Ra) may play an important role in cartilage degradation by inhibiting IL-1 activity and therefore blocking IL-1 stimulation of prostaglandin E2 (PGE2) synthesis. Nitric oxide (NO) formation is increased during inflammation. High concentrations of NO exert negative effects on chondrocyte functions. We investigated the possible effects of 3 different nonsteroidal antiinflammatory drugs (NSAID; aceclofenac, piroxicam, aspirin) on IL-1Ra and NO production in human articular chondrocytes. METHODS: Normal and osteoarthritic (OA) cartilage samples were obtained from autopsy and prosthetic joint surgery, respectively. Chondrocytes were isolated and stimulated with 4 different stimuli: IL-1, tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and insulin-like growth factor (IGF). The 3 NSAID were added simultaneously to each different concentration of stimulus. IL-1Ra was measured in supernatant by ELISA; nitrites were quantified by the Griess reaction; PGE2 level was measured by enzyme immunoassay. RESULTS: OA samples spontaneously produced higher levels of IL-1Ra than normal samples (130+/-2.3 vs 30+/-3.1 pg/mI). IL-1, TNF-alpha, and LPS produced dose dependent increases in synthesis of IL-1Ra. In their presence, IL-1Ra was detected in supernatant at 48 h, but its highest level was measured at 144 h. The most potent stimulus was IL 1, followed by TNF-alpha. Fetal bovine serum and IGF in turn did not modify the basal levels of IL-1Ra. In contrast to piroxicam and aspirin, aceclofenac 10 microg/ml and TNF-alpha 10 ng/ml increased almost 46 times the basal amount of IL 1Ra produced by OA chondrocytes. Additionally, aceclofenac and aspirin inhibited NO synthesis. Finally, the 3 NSAID reduced the levels of PGE2 detected after stimulation with IL-1. CONCLUSION: Proinflammatory stimuli induce IL-IRa synthesis in human articular chondrocytes. Aceclofenac may modulate PGE2 production by increasing IL-IRa production and decreasing NO synthesis. Some NSAID exert diverse prostaglandin independent effects. PMID- 11764220 TI - Precision of composite measures of osteoarthritis efficacy in comparison to that of individual endpoints. AB - OBJECTIVE: Osteoarthritis (OA) clinical studies generally employ various endpoints to evaluate a spectrum of disease manifestations. Compared with individual endpoints, a composite measure might (1) provide a uniform outcome measure of OA efficacy with greater face validity, (2) address multiplicity, and (3) enhance precision. Combinations of endpoints were analyzed to investigate precision of composite measures of OA efficacy. METHODS: We reanalyzed three 6 week, placebo controlled, double blind, parallel group studies (2 by the same protocol) of the cyclooxygenase-2 (COX-2) specific inhibitor rofecoxib. The average change from baseline at study weeks 2, 4, and 6 was assessed for 10 individual response variables, including patient and investigator global assessments, WOMAC 3.0V OA Index pain, stiffness and physical function subscales, graded study joint tenderness, and rescue analgesic use. Relationships among variables were evaluated using pairwise correlations and principal components analysis. The precision of variables to differentiate rofecoxib from placebo was evaluated using effect size (i.e., mean difference between rofecoxib versus placebo divided by pooled SD). RESULTS: Correlations among all pairs of response variables ranged from 0.5 to 0.9, except those with tenderness (0.4 to 0.6) and those with analgesic use (0.2 to 0.4). The first principal component explained about 70% of the total variability, with weights generally similar (0.17 for rescue analgesic use, 0.25 for tenderness, and 0.30 to 0.37 for the others). These results indicate that nearly all measures are closely related. Based on these results, various linear combinations of the 9 endpoints were formed and their precision to discriminate active treatment from placebo was compared to that of the individual endpoints. Effect sizes of the individual endpoints ranged from 0.6 to 1.1; those of the composites from 0.7 to 0.9. The results were very consistent between study protocols. CONCLUSION: In comparison to individual endpoints, composite analyses of OA clinical endpoints do not increase precision to discriminate active treatment from placebo. PMID- 11764221 TI - Effect of a novel insole on the subtalar joint of patients with medial compartment osteoarthritis of the knee. AB - OBJECTIVE: To assess the efficacy of a lateral wedge insole with elastic strapping of the subtalar joint for conservative treatment of osteoarthritis (OA) of the knee. METHODS: The efficacy of a novel insole with elastic subtalar strapping and a traditional shoe insert wedge insole was compared. Ninety female outpatients with OA of the knee were treated with wedge insoles for 8 weeks. Randomization was performed according to birth date. Standing radiographs with unilateral insole use were used to analyze the femorotibial and talar tilt angles for each patient with and without their respective insole. Visual analog scale (VAS) score for subjective knee pain at the final assessment was compared with that at baseline in both groups. RESULTS: Participants wearing the elastically strapped insole (n = 46) had significantly decreased femorotibial angle (p < 0.0001) and talar tilt angle (p = 0.005) and significantly improved VAS pain score (p = 0.045) in comparison with baseline assessments. These significant differences were not found in the group with the inserted insole (n = 44). CONCLUSION: The novel strapped insole leads to valgus angulation of the talus, resulting in correction of the femorotibial angle in patients with knee OA with varus deformity, and may have a therapeutic effect similar to that of high tibial osteotomy. PMID- 11764222 TI - Effects of social support and education on health care costs for patients with fibromyalgia. AB - OBJECTIVE: The rising costs of health care are of great concern, particularly for the chronically ill. Interventions that promote health status and well being while teaching appropriate use of the health care system have led to cost savings among patients with osteoarthritis. We carried out social support and education interventions with patients with fibromyalgia (FM) and assessed the effect on health care costs, psychosocial variables, and health status. METHODS: Participants were 600 patients with FM who were members of a health maintenance organization. They were randomly assigned to one of 2 experimental groups (social support; social support and education) or to a no-treatment control group. Assessments were conducted at baseline and following a one year intervention. Health care cost data were obtained directly from participants' medical records. RESULTS: Results indicated significant reductions in all groups' costs of prescriptions, laboratory tests, and visits to a nurse, nurse practitioner and/or physicians' assistant. All groups also showed improvements on variables assessing effect of FM, self-efficacy, depression, and knowledge of FM. The social support and education group was less helpless after one year than the other groups; differential changes for all other variables were not significant. CONCLUSION: The study did not reveal differential changes in health care costs among participants in the experimental and control groups. These findings emphasize the importance of using objective health care utilization data when calculating health care costs, as well as the value of including a no-treatment control group to prevent erroneous conclusions about treatment efficacy. PMID- 11764223 TI - Viscoelastic properties and flexibility of the human muscle-tendon unit in benign joint hypermobility syndrome. AB - OBJECTIVE: To examine the passive energy absorption of the hamstring muscle tendon unit in 9 women with benign joint hypermobility syndrome (BJHS) and 9 age and sex matched controls. METHODS: Resistance to stretch was measured as knee flexion moment (N.m) with an isokinetic dynamometer during passive knee extension. The angle that induced a stretch sensation without pain was the maximal stretch angle. Force, angle, angular velocity (0.09 rad/s), and electromyograph were simultaneously and continuously recorded during the stretch. Hamstring cross sectional area was obtained with magnetic resonance imaging. RESULTS: Forearm skin extensibility was greater for BJHS (3.6+/-0.5 cm) than for controls (1.3+/-0.2 cm) (p < 0.01). Similarly, the Beighton score was greater for BJHS (6.6+/-0.8) than for controls (0.4+/-0.2) (p < 0.001). Maximal stretch angle was greater for BJHS (delta1.35+/-0.07 rad) compared to controls (delta0.98+/ 0.05 rad) (p < 0.001), and the corresponding peak moment was also greater for BJHS (1.3+/-0.4 Nm/cm2) than for controls (0.6+/-0.1 Nm/cm2) (p < 0.01). For a given mutual angle the passive energy absorption was the same for both groups, but at the maximal stretch angle the total area-normalized energy was greater for BJHS (0.36+/-0.04 J/cm2) than for controls (0.18+/-0.28 J/cm2) (p < 0.001). CONCLUSION: The lack of difference in passive energy absorption for a given mutual stretch angle suggests that passive properties of the muscle-tendon unit of BJHS are similar to those of controls. However, the greater maximal stretch angle and corresponding peak moment in BJHS suggests a greater subjective tolerance to passive stretch. That is, increased flexibility in BJHS is not a function of altered passive properties of the muscle-tendon complex. It remains unknown if the enhanced tolerance to passive tension plays a role in the development of musculoskeletal ailment. PMID- 11764224 TI - Validation of beighton score and prevalence of connective tissue signs in 773 Dutch children. AB - OBJECTIVE: Validation of the Beighton Score and the prevalence of connective tissue signs were investigated in Dutch children. METHODS: Hypermobility investigation according to Beighton was undertaken in 773 healthy children aged 4 12 years. An inventory of the signs that fitted with connective tissue disorders was compiled. RESULTS: The percentage of general hypermobility at a cutoff point of > or = 4 was 26.5% (range 11.4-49%) in children aged 4-9 yrs. At the age of 10 12 yrs, this percentage was 5.3% (range 0-7.1%). There was good agreement (kappa = 0.65) between the measurement on the left and the right sides at all ages. Of the investigated connective tissue signs, thin transparent skin was noted in 0.1%, blue sclerae in 0.1%, and an elevated palate in 2.3% of the children. It was observed that 8.2% of the children were able to touch their nose with their tongue (Gorlin's sign) and 23.7% were able to touch their chin. The other signs were not observed in any of the children. CONCLUSION: We validated the criteria for performing the Beighton Score in (Dutch) children. A cutoff point of > or = 5 should be chosen for Dutch children aged between 4 and 9 years. It appeared that one-sided Beighton Score could be determined during screening of healthy populations. Additional diagnostic tests are warranted if one of the following signs, such as a thin transparent skin, hyperelastic skin, large hematomas, prominent scars, molluscoid tumors, striae distensae, blue sclerae, elevated palate, and Gorlin's sign, is encountered in a child. Although it is not possible to extrapolate the data, we expect that the findings are relevant for children of Caucasian race. PMID- 11764225 TI - Evaluation of ILAR classification criteria for juvenile idiopathic arthritis in Spanish children. AB - OBJECTIVE: To evaluate the proposed International League of Associations for Rheumatology (ILAR) classification criteria for juvenile idiopathic arthritis in a cohort of Spanish children. METHODS: One hundred twenty-five patients with chronic arthritis were categorized according to one of the traditional classifications and the proposed ILAR classification system after at least 6 months of disease. The traditional classifications included the European League Against Rheumatism (EULAR) criteria for pauciarticular, polyarticular rheumatoid factor (RF) negative, and systemic juvenile chronic arthritis (JCA), as well as for RF+ polyarthritis; the Vancouver criteria for juvenile psoriatic arthritis (JPsA); and the European Spondylarthropathy Study Group (ESSG) preliminary criteria for juvenile spondyloarthropathy (JSpA). RESULTS: The ILAR criteria classified 106/125 patients (84.8%). All patients with systemic and polyarticular JCA, RF+ polyarthritis, and definite juvenile psoriatic arthritis were reclassified in the corresponding ILAR category. In contrast, only 80% of pauciarticular JCA and 47% of JSpA patients could be allocated to the ILAR oligoarthritis (47/59 patients, 35 persistent and 12 extended) and enthesitis related arthritis (ErA. 8/17 patients) categories. Two children with probable PsA were reclassified in the RF- polyarthritis category. Nineteen patients (15.2%) were allocated to the ILAR "other arthritis" group, 13/19 because they did not fulfill criteria for any of the other categories (12 due to family history of psoriasis and one because of family history of HLA-B27 associated disease). The remaining 6 patients met criteria for 2 categories, RF- polyarthritis and either ErA (n = 5) or PsA (n = 1). No differences other than family history of psoriasis were found in any of the variables studied between pauciarticular JCA patients classified in the oligoarthritis (n = 47) and those in the "other arthritis" (n = 11) ILAR categories. CONCLUSION: The proposed ILAR criteria allocated 84.8% of the patients classified by traditional criteria. Family history of psoriasis (n = 12) and polyarticular onset of disease in patients with ErA (n = 5) were responsible for most of the exclusions from other ILAR categories. PMID- 11764226 TI - Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism. AB - OBJECTIVE: New classification criteria (ILAR) have been proposed for juvenile idiopathic arthritis (JIA). They are more descriptive than those formerly used [American College of Rheumatology (ACR), European League Against Rheumatism (EULAR)], but require validation against classifications already in use. We validated the ILAR criteria in relation to the EULAR criteria in a prospective, incidence, and population based setting, and analyzed their feasibility. METHODS: Construct validity of ILAR and EULAR classification criteria refers to how closely the 2 instruments are related and how each of them operates in classifying subgroups/categories. Twenty doctors in 5 Nordic countries collected data from the incidence cases within their catchment areas during an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: A total of 322 patients were included. Classification according to the ILAR criteria was possible in 321 patients; 290 patients had a disease duration > or = 3 months and were classified according to the EULAR criteria. One child could only be classified according to the EULAR criteria. Thus, 31/322 (9.6%) children were classified according to the ILAR criteria only. Forty-eight of 321 (15%) patients did not fit into any category and 6% (20/321) fulfilled criteria for2 categories. In the ILAR classification 5 out of 7 categories/subgroups have 2 to 5 specified exclusion criteria that highly discriminate the definition of each patient. In our study the exclusion criteria were fulfilled to only a small extent. CONCLUSION: The EULAR and ILAR criteria differ concerning the operational definitions of the subvariables involved, which complicates their comparison. By using ILAR rather than EULAR criteria the number of cases with juvenile arthritis increased by 10%, considering the first half-year after onset. The validity of the ILAR criteria is low since they often exclude patients from subgroup classification and the possibility of having more than one diagnosis is not negligible. The specified exclusion criteria for some of the subgroups are difficult to fulfill in clinical work and variables involved could be questioned with regard to their consistency. PMID- 11764227 TI - De novo production of IgG antinuclear antibodies in a neonate. AB - We describe the first case in which de novo production of multiple IgG antinuclear antibodies (ANA) occurred in a female neonate of an ANA negative mother. The infant presented at 4 weeks of age with hemorrhagic panencephalitis, diffuse intraparenchymal hemorrhages, and straight sinus thrombosis. She had been vaccinated against hepatitis B at birth. No other cause was found and maternal prenatal care was unremarkable. The infant's screening ANA test by ELISA was positive at 6 weeks with specificity for ssDNA, Sm, and nRNP/Sm. At 8 weeks antibodies to dsDNA and centromere were detected as well. By 8 months, she still had slightly elevated anti-dsDNA, Sm, and nRNP/Sm antibodies. The ANA test by immunofluorescence was abnormal at 8 weeks through 13 weeks with centromere and then homogeneous pattern. Based on similarities with other reported cases, we speculate that hepatitis B vaccination may have been involved in the development of antinuclear antibodies. PMID- 11764228 TI - Acquired Brown's syndrome in a child with poststreptococcal reactive arthritis. AB - Acquired Brown's syndrome is a disorder of ocular mobility characterized by the inability to elevate the affected eye in full adduction owing to inflammatory tenosynovitis of the superior oblique tendon. We describe a child who developed Brown's syndrome as a complication of poststreptococcal reactive arthritis. PMID- 11764229 TI - False positive elevation of cardiac troponin I in seropositive rheumatoid arthritis. AB - Cardiac troponin I is a sensitive and specific biochemical marker for the diagnosis of acute myocardial injury. We describe a patient with seropositive rheumatoid arthritis (RA) in whom troponin I, measured with a microparticle enzyme immunoassay, was elevated falsely in the absence of acute myocardial infarction. Apparent elevation of troponin I concentration should be evaluated with care in patients with seropositive RA. PMID- 11764230 TI - Takayasu arteritis and atherosclerosis: illustrating the consequences of endothelial damage. AB - The excess of cardiovascular morbidity associated with chronic vasculitic disease has become a focus of considerable research, particularly regarding the link between endothelial damage and the development of atherosclerosis. We describe a case of Takayasu arteritis treated sub-optimally by today's standards, giving rise to an 11 year history of progressive, stepwise decline associated with cerebrovascular events and leading to early death. Postmortem findings presented a picture of chronic atherosclerotic disease but in a distribution consistent with lesions of Takayasu arteritis. PMID- 11764231 TI - Treatment of refractory symphysitis pubis with intravenous pamidronate. AB - Osteitis pubis is a noninfectious painful inflammatory disorder of the symphysis pubis. Etiologic factors include urologic procedures, abdomino-perineal and gynecological surgery, and spondyloarthropathies, although many cases are idiopathic. Most respond to conservative measures consisting primarily of rest and analgesic/antiinflammatory agents. We describe 3 cases, 2 with idiopathic osteitis pubis and one that was associated with a spondyloarthropathy, that failed to respond to conservative measures but experienced clinical remission with 3 to 6 monthly courses of intravenous pamidronate. Remission was also evident in 2 patients on isotope bone scan. Followup has revealed no recurrence. Intravenous pamidronate may constitute a safe and effective treatment option for patients with refractory osteitis pubis. PMID- 11764232 TI - Localized polyarteritis nodosa with periostitis. PMID- 11764233 TI - Silicone gel breast implants. PMID- 11764234 TI - Silicone gel breast implants. PMID- 11764235 TI - Fibromyalgia: can one distinguish it from simulation? PMID- 11764236 TI - Unusual synovial cyst of the knee treated with fibrin sealant. PMID- 11764237 TI - Assessment of prothrombotic risk in patients with Behcet's disease should include homocysteine plasma levels. PMID- 11764238 TI - On estimating medical cost and incremental cost-effectiveness ratios with censored data. AB - Medical cost estimation is very important to health care organizations and health policy makers. We consider cost-effectiveness analysis for competing treatments in a staggered-entry, survival-analysis-based clinical trial. We propose a method for estimating mean medical cost over patients in such settings. The proposed estimator is shown to be consistent and asymptotically normal, and its asymptotic variance can be obtained. In addition, we propose a method for estimating the incremental cost-effectiveness ratio and for obtaining a confidence interval for it. Simulation experiments are conducted to evaluate our proposed methods. Finally, we apply our methods to a clinical trial comparing the cost effectiveness of implanted cardiac defibrillators with conventional therapy for individuals at high risk for ventricular arrhythmias. PMID- 11764239 TI - Testing the independence of two diagnostic tests. AB - Consider two diagnostic procedures having binary outcomes. If one of the tests results in a positive finding, a more definitive diagnostic procedure will be administered to establish the presence or absence of a disease. The use of both tests will improve the overall screening sensitivity when the two tests are independent, compared with employing two tests that are positively correlated. We estimate the correlation coefficient of the two tests and derive statistical methods for testing the independence of the two diagnostic procedures conditional on disease status. The statistical tests are used to investigate the independence of mammography and clinical breast exams aimed at establishing the benefit of early detection of breast cancer. The data used in the analysis are obtained from periodic screening examinations of three randomized clinical trials of breast cancer screening. Analysis of each of these trials confirms the independence of the clinical breast and mammography examinations. Based on these three large clinical trials, we conclude that a clinical breast exam considerably increases the overall sensitivity relative to screening with mammography alone and should be routinely included in early breast cancer detection programs. PMID- 11764240 TI - Dose-finding designs for HIV studies. AB - We present a class of simple designs that can be used in early dose-finding studies in HIV. Such designs, in contrast with Phase I designs in cancer, have a lot of the Phase II flavor about them. Information on efficacy is obtained during the trial and is as important as that relating to toxicity. The designs proposed here sequentially incorporate the information obtained on viral reduction. Initial doses are given from some fixed range of dose regimens. The doses are ordered in terms of their toxic potential. At any dose, a patient can have one of three outcomes: inability to take the treatment (toxicity), ability to take the treatment but insufficient reduction in viral load (viral failure), and ability to take the treatment as well as a sufficient reduction of viral load (success). A clear goal for some class of designs would be the identification of the dose leading to the greatest percentage of successes. Under certain assumptions, which we identify and discuss, we can obtain efficient designs for this task. Under weaker, sometimes more realistic assumptions, we can still obtain designs that have good operating characteristics in identifying a level, if such a level exists, having some given or greater success rate. In the absence of such a level, the designs will come to an early closure, indicating the ineffectiveness of the new treatment. PMID- 11764241 TI - Causal inference on the difference of the restricted mean lifetime between two groups. AB - When comparing survival times between two treatment groups, it may be more appropriate to compare the restricted mean lifetime, i.e., the expectation of lifetime restricted to a time L, rather than mean lifetime in order to accommodate censoring. When the treatments are not assigned to patients randomly, as in observational studies, we also need to account for treatment imbalances in confounding factors. In this article, we propose estimators for the difference of the restricted mean lifetime between two groups that account for treatment imbalances in prognostic factors assuming a proportional hazards relationship. Large-sample properties of our estimators based on martingale theory for counting processes are also derived. Simulation studies were conducted to compare these estimators and to assess the adequacy of the large-sample approximations. Our methods are also applied to an observational database of acute coronary syndrome patients from Duke University Medical Center to estimate the treatment effect on the restricted mean lifetime over 5 years. PMID- 11764242 TI - One-sided tests in clinical trials with multiple endpoints. AB - Treatment comparisons in clinical trials often involve several endpoints. For example, one might wish to demonstrate that a new treatment is superior to the current standard for some components of the multivariate response vector and is not inferior, modulo biologically unimportant difference to the standard treatment for all other components. We introduce a new approach to multiple endpoint testing that incorporates the essential univariate and multivariate features of the treatment effects. This approach is compared with existing methods in a simulation study and applied to data on rheumatoid arthritis patients receiving one of two treatments. PMID- 11764243 TI - Estimation of the timing of perinatal transmission of HIV. AB - Knowledge of the timing of perinatal transmission of HIV would be valuable for the determination and evaluation of preventive treatments and would shed light on the mechanism of transmission. Estimation of the distribution of the time of perinatal transmission is difficult, however, because tests of infection status can only be undertaken after birth. DNA and RNA polymerase chain reaction (PCR) assays and HIV culture have been the most commonly used diagnostic tests for perinatal HIV infection. Such tests have high sensitivity and specificity, except when they are given shortly after infection. In this paper we use the time dependent sensitivity of these diagnostic tests to make nonparametric and semiparametric inferences about the distribution of the time of perinatal HIV transmission as well as the cumulative probability of perinatal transmission. The methods are illustrated with data from a clinical trial conducted by the AIDS Clinical Trials group. PMID- 11764244 TI - Bayesian modeling of age-specific survival in nesting studies under Dirichlet priors. AB - There has been much work done in nest survival analysis using the maximum likelihood (ML) method. The ML method suffers from the instability of numerical calculations when models having a large number of unknown parameters are used. A Bayesian approach of model fitting is developed to estimate age-specific survival rates for nesting studies using a large class of prior distributions. The computation is done by Gibbs sampling. Some latent variables are introduced to simplify the full conditional distributions. The method is illustrated using both a real and a simulated data set. Results indicate that Bayesian analysis provides stable and accurate estimates of nest survival rates. PMID- 11764245 TI - Bayesian modeling of the level and duration of fertility in the menstrual cycle. AB - Time to pregnancy studies that identify ovulation days and collect daily intercourse data can be used to estimate the day-specific probabilities of conception given intercourse on a single day relative to ovulation. In this article, a Bayesian semiparametric model is described for flexibly characterizing covariate effects and heterogeneity among couples in daily fecundability. The proposed model is characterized by the timing of the most fertile day of the cycle relative to ovulation, by the probability of conception due to intercourse on the most fertile day, and by the ratios of the daily conception probabilities for other days of the cycle relative to this peak probability. The ratios are assumed to be increasing in time to the peak and decreasing thereafter. Generalized linear mixed models are used to incorporate covariate and couple specific effects on the peak probability and on the day-specific ratios. A Markov chain Monte Carlo algorithm is described for posterior estimation, and the methods are illustrated through application to caffeine data from a North Carolina pregnancy study. PMID- 11764246 TI - Statistical analysis of uniparental disomy data using hidden Markov models. AB - Genetic studies of uniparental disomy (UPD) employing many markers have helped geneticists to gain a better understanding of the molecular mechanisms underlying nondisjunction. However, most existing methods cannot simultaneously analyze all genetic markers and consistently incorporate crossover interference; they thus fail to make the most use of genetic information in the data. In the present article, we describe a hidden Markov model for multilocus uniparental disomy data. This method is based on the chi-square model for the crossover process and can simultaneously incorporate all marker information including untyped and uninformative markers. We then apply this novel method to analyze a set of UPD15 data. PMID- 11764247 TI - Most powerful permutation invariant tests for relatedness hypotheses using genotypic data. AB - The problem of inferring kinship structure among a sample of individuals using genetic markers is considered with the objective of developing hypothesis tests for genetic relatedness with nearly optimal properties. The class of tests considered are those that are constrained to be permutation invariant, which in this context defines tests whose properties do not depend on the labeling of the individuals. This is appropriate when all individuals are to be treated identically from a statistical point of view. The approach taken is to derive tests that are probably most powerful for a permutation invariant alternative hypothesis that is, in some sense, close to a null hypothesis of mutual independence. This is analagous to the locally most powerful test commonly used in parametric inference. Although the resulting test statistic is a U-statistic, normal approximation theory is found to be inapplicable because of high skewness. As an alternative it is found that a conditional procedure based on the most powerful test statistic can calculate accurate significance levels without much loss in power. Examples are given in which this type of test proves to be more powerful than a number of alternatives considered in the literature, including Queller and Goodknight's (1989) estimate of genetic relatedness, the average number of shared alleles (Blouin, 1996), and the number of feasible sibling triples (Almudevar and Field, 1999). PMID- 11764248 TI - Decision-theoretic designs for pre-phase II screening trials in oncology. AB - A Bayesian decision-theoretic method is proposed for conducting small, randomized pre-phase II selection trials. The aim is to improve on the design of Thall and Estey (1993, Statistics in Medicine 12, 1197-1211). Designs are derived that optimize a gain function accounting for current and future patient gains, per patient cost, and future treatment development cost. To reduce the computational burden associated with backward induction, myopic versions of the design that consider only one, two, or three future decisions at a time are also considered. The designs are compared in the context of a screening trial in acute myelogenous leukemia. PMID- 11764249 TI - Inverse adaptive cluster sampling. AB - Consider a population in which the variable of interest tends to be at or near zero for many of the population units but a subgroup exhibits values distinctly different from zero. Such a population can be described as rare in the sense that the proportion of elements having nonzero values is very small. Obtaining an estimate of a population parameter such as the mean or total that is nonzero is difficult under classical fixed sample-size designs since there is a reasonable probability that a fixed sample size will yield all zeroes. We consider inverse sampling designs that use stopping rules based on the number of rare units observed in the sample. We look at two stopping rules in detail and derive unbiased estimators of the population total. The estimators do not rely on knowing what proportion of the population exhibit the rare trait but instead use an estimated value. Hence, the estimators are similar to those developed for poststratification sampling designs. We also incorporate adaptive cluster sampling into the sampling design to allow for the case where the rare elements tend to cluster within the population in some manner. The formulas for the variances of the estimators do not allow direct analytic comparison of the efficiency of the various designs and stopping rules, so we provide the results of a small simulation study to obtain some insight into the differences among the stopping rules and sampling approaches. The results indicate that a modified stopping rule that incorporates an adaptive sampling component and utilizes an initial random sample of fixed size is the best in the sense of having the smallest variance. PMID- 11764250 TI - Matched case-control data analysis with selection bias. AB - Case-control studies offer a rapid and efficient way to evaluate hypotheses. On the other hand, proper selection of the controls is challenging, and the potential for selection bias is a major weakness. Valid inferences about parameters of interest cannot be drawn if selection bias exists. Furthermore, the selection bias is difficult to evaluate. Even in situations where selection bias can be estimated, few methods are available. In the matched case-control Northern Manhattan Stroke Study (NOMASS), stroke-free controls are sampled in two stages. First, a telephone survey ascertains demographic and exposure status from a large random sample. Then, in an in-person interview, detailed information is collected for the selected controls to be used in a matched case-control study. The telephone survey data provides information about the selection probability and the potential selection bias. In this article, we propose bias-corrected estimators in a case-control study using a joint estimating equation approach. The proposed bias-corrected estimate and its standard error can be easily obtained by standard statistical software. PMID- 11764251 TI - Using open robust design models to estimate temporary emigration from capture recapture data. AB - Capture-recapture studies are crucial in many circumstances for estimating demographic parameters for wildlife and fish populations. Pollock's robust design, involving multiple sampling occasions per period of interest, provides several advantages over classical approaches. This includes the ability to estimate the probability of being present and available for detection, which in some situations is equivalent to breeding probability. We present a model for estimating availability for detection that relaxes two assumptions required in previous approaches. The first is that the sampled population is closed to additions and deletions across samples within a period of interest. The second is that each member of the population has the same probability of being available for detection in a given period. We apply our model to estimate survival and breeding probability in a study of hawksbill sea turtles (Eretmochelys imbricata), where previous approaches are not appropriate. PMID- 11764252 TI - Threshold model for misclassified binary responses with applications to animal breeding. AB - A Bayesian procedure for misclassified binary data was developed. An animal breeding simulation indicated that, when error of classification was ignored, the variance between clusters was inferred incorrectly. Data were reanalyzed assuming that the probability of misclassification was either known or unknown. In the first case, input parameter values were recovered in the analysis. When the probability was unknown, there was a slight bias; the true probability of misclassification and the true number of miscoded observations appeared within high credibility regions. An analysis of fertility in dairy cows is presented. PMID- 11764253 TI - Line transect sampling in small regions. AB - This article develops an approach to estimating population abundance from line transect surveys that uses a calibration survey to estimate the detection function, which is then employed as a weight function in constructing the abundance estimate. Nonparametric methods of estimating the detection function via local regression and via a kernel density estimator are considered. The proposed methods are evaluated using a set of Western Australian plant data and weed enumeration data. PMID- 11764254 TI - Analyzing variety by environment data using multiplicative mixed models and adjustments for spatial field trend. AB - The recommendation of new plant varieties for commercial use requires reliable and accurate predictions of the average yield of each variety across a range of target environments and knowledge of important interactions with the environment. This information is obtained from series of plant variety trials, also known as multi-environment trials (MET). Cullis, Gogel, Verbyla, and Thompson (1998) presented a spatial mixed model approach for the analysis of MET data. In this paper we extend the analysis to include multiplicative models for the variety effects in each environment. The multiplicative model corresponds to that used in the multivariate technique of factor analysis. It allows a separate genetic variance for each environment and provides a parsimonious and interpretable model for the genetic covariances between environments. The model can be regarded as a random effects analogue of AMMI (additive main effects and multiplicative interactions). We illustrate the method using a large set of MET data from a South Australian barley breeding program. PMID- 11764255 TI - Closed-form approximations to the REML estimator of a variance ratio (or heritability) in a mixed linear model. AB - In this article, we estimate heritability or intraclass correlation in a mixed linear model having two sources of variation. In most applications, the commonly used restricted maximum likelihood (REML) estimator can only be obtained via an iterative approach. In some cases, the algorithm used to compute REML estimates may be slow or may even fail to converge. We develop a set of closed-form approximations to the REML estimator, and the performance of these estimators is compared with that of the REML estimator. We provide guidelines regarding how to choose the estimator that best approximates the REML estimator. Examples presented in the article suggest that the closed-form estimators compete with and, in some cases, outperform the REML estimator. PMID- 11764256 TI - Tests against qualitative interaction: exact critical values and robust tests. AB - Consider a study to evaluate treatment A with a placebo in two or more groups of patients. If treatment A is beneficial to one group of patients and harmful to another, then we say that there is qualitative interaction or crossover interaction between patient groups and the treatments. Gail and Simon (1985, Biometrics 41, 361-372) developed a large-sample procedure for this testing problem. Their test has received favorable coverage in the literature. In this article, we obtain corresponding exact finite sample results for normal error distribution and provide a table of critical values. The test statistic is similar to the familiar F-ratio, and its p-value is equal to a weighted sum of tail areas of F-distributions. The computations to implement this are simple. A simulation study shows that the exact critical values provided here for normal error distribution are preferable to the asymptotic critical values for a wide range of error distributions. We also develop tests that are power robust against long-tailed error distributions. Our robust test uses M-estimators instead of the least squares estimators. We show that the efficiency robustness of the M estimator translates to power robustness of the corresponding test. Therefore, our robust tests are better if outliers are expected. A simulation study illustrates the substantial power advantages of our robust tests. PMID- 11764257 TI - Local influence to detect influential data structures for generalized linear mixed models. AB - This article discusses the generalization of the local influence measures for normally distributed responses to local influence measures for generalized linear models with random effects. For these models, it is shown that the subject oriented influence measure is a special case of the proposed observation-oriented influence measure. A two-step diagnostic procedure is proposed. The first step is to search for influential subjects. A search for influential observations is proposed as the second step. An illustration of a two-treatment, multiple-period crossover trial demonstrates the practical importance of the detection of influential observations in addition to the detection of influential subjects. PMID- 11764258 TI - Shrinkage estimators for covariance matrices. AB - Estimation of covariance matrices in small samples has been studied by many authors. Standard estimators, like the unstructured maximum likelihood estimator (ML) or restricted maximum likelihood (REML) estimator, can be very unstable with the smallest estimated eigenvalues being too small and the largest too big. A standard approach to more stably estimating the matrix in small samples is to compute the ML or REML estimator under some simple structure that involves estimation of fewer parameters, such as compound symmetry or independence. However, these estimators will not be consistent unless the hypothesized structure is correct. If interest focuses on estimation of regression coefficients with correlated (or longitudinal) data, a sandwich estimator of the covariance matrix may be used to provide standard errors for the estimated coefficients that are robust in the sense that they remain consistent under misspecification of the covariance structure. With large matrices, however, the inefficiency of the sandwich estimator becomes worrisome. We consider here two general shrinkage approaches to estimating the covariance matrix and regression coefficients. The first involves shrinking the eigenvalues of the unstructured ML or REML estimator. The second involves shrinking an unstructured estimator toward a structured estimator. For both cases, the data determine the amount of shrinkage. These estimators are consistent and give consistent and asymptotically efficient estimates for regression coefficients. Simulations show the improved operating characteristics of the shrinkage estimators of the covariance matrix and the regression coefficients in finite samples. The final estimator chosen includes a combination of both shrinkage approaches, i.e., shrinking the eigenvalues and then shrinking toward structure. We illustrate our approach on a sleep EEG study that requires estimation of a 24 x 24 covariance matrix and for which inferences on mean parameters critically depend on the covariance estimator chosen. We recommend making inference using a particular shrinkage estimator that provides a reasonable compromise between structured and unstructured estimators. PMID- 11764259 TI - Linear equality constraints in the general linear mixed model. AB - Scientists may wish to analyze correlated outcome data with constraints among the responses. For example, piecewise linear regression in a longitudinal data analysis can require use of a general linear mixed model combined with linear parameter constraints. Although well developed for standard univariate models, there are no general results that allow a data analyst to specify a mixed model equation in conjunction with a set of constraints on the parameters. We resolve the difficulty by precisely describing conditions that allow specifying linear parameter constraints that insure the validity of estimates and tests in a general linear mixed model. The recommended approach requires only straightforward and noniterative calculations to implement. We illustrate the convenience and advantages of the methods with a comparison of cognitive developmental patterns in a study of individuals from infancy to early adulthood for children from low-income families. PMID- 11764260 TI - Multiple imputation methods for estimating regression coefficients in the competing risks model with missing cause of failure. AB - We propose a method to estimate the regression coefficients in a competing risks model where the cause-specific hazard for the cause of interest is related to covariates through a proportional hazards relationship and when cause of failure is missing for some individuals. We use multiple imputation procedures to impute missing cause of failure, where the probability that a missing cause is the cause of interest may depend on auxiliary covariates, and combine the maximum partial likelihood estimators computed from several imputed data sets into an estimator that is consistent and asymptotically normal. A consistent estimator for the asymptotic variance is also derived. Simulation results suggest the relevance of the theory in finite samples. Results are also illustrated with data from a breast cancer study. PMID- 11764261 TI - Small-sample adjustments for Wald-type tests using sandwich estimators. AB - The sandwich estimator of variance may be used to create robust Wald-type tests from estimating equations that are sums of K independent or approximately independent terms. For example, for repeated measures data on K individuals, each term relates to a different individual. These tests applied to a parameter may have greater than nominal size if K is small, or more generally if the parameter to be tested is essentially estimated from a small number of terms in the estimating equation. We offer some practical modifications to these robust Wald type tests, which asymptotically approach the usual robust Wald-type tests. We show that one of these modifications provides exact coverage for a simple case and examine by simulation the modifications applied to the generalized estimating equations of Liang and Zeger (1986), conditional logistic regression, and the Cox proportional hazard model. PMID- 11764262 TI - Utilizing propensity scores to estimate causal treatment effects with censored time-lagged data. AB - Observational studies frequently are conducted to compare long-term effects of treatments. Without randomization, patients receiving one treatment are not guaranteed to be prognostically comparable to those receiving another treatment. Furthermore, the response of interest may be right-censored because of incomplete follow-up. Statistical methods that do not account for censoring and confounding may lead to biased estimates. This article presents a method for estimating treatment effects in nonrandomized studies with right-censored responses. We review the assumptions required to estimate average causal effects and derive an estimator for comparing two treatments by applying inverse weights to the complete cases. The weights are determined according to the estimated probability of receiving treatment conditional on covariates and the estimated treatment specific censoring distribution. By utilizing martingale representations, the estimator is shown to be asymptotically normal and an estimator for the asymptotic variance is derived. Simulation results are presented to evaluate the properties of the estimator. These methods are applied to an observational data set of acute coronary syndrome patients from Duke University Medical Center to estimate the effect of a treatment strategy on the mean 5-year medical cost. PMID- 11764264 TI - Assessing homeostasis through circadian patterns. AB - An organism is thought to be in a dynamic state of homeostasis when each physiological and behavioral system reaches a delicate balance within the framework of other regulatory processes. Many biological systems target specific set-point variables and generate circadian patterns. In this article, we focus on specific measurements representative of two systems, namely deep-body temperature and activity counts. We examine data collected every 30 minutes in mice, assume there are underlying circadian patterns, and extend the approach presented in Brumback and Rice (1998, Journal of the American Statistical Association 93, 961 976) in order to obtain estimates in the presence of correlated data. We then assess homeostasis using these estimates and their statistical properties. PMID- 11764263 TI - Tests for order restrictions in binary data. AB - In this article, a general procedure is presented for testing for equality of k independent binary response probabilities against any given ordered alternative. The proposed methodology is based on an estimation procedure developed in Hwang and Peddada (1994, Annals of Statistics 22, 67-93) and can be used for a very broad class of order restrictions. The procedure is illustrated through application to two data sets that correspond to three commonly encountered order restrictions: simple tree order, simple order, and down turn order. PMID- 11764265 TI - Correlating two viral load assays with known detection limits. AB - A timely objective common to many HIV studies involves assessing the correlation between two different measures of viral load obtained from each of a sample of patients. This correlation has scientific utility in a number of contexts, including those aimed at a comparison of competing assays for quantifying virus and those aimed at determining the level of association between viral loads in two different reservoirs using the same assay. A complication for the analyst seeking valid point and interval estimates of such a correlation is the fact that both variables may be subject to left censoring due to values below assay detection limits. We address this problem using a bivariate normal likelihood that accounts for left censoring of two variables that may have different detection limits. We provide simulation results to evaluate sampling properties of the resulting correlation estimator and compare it with ad hoc estimators in the presence of nondetects. In an effort to obtain improved confidence interval properties relative to the Wald approach, we evaluate and compare profile likelihood-based intervals. We apply the methods to HIV viral load data on women and infants from a trial in Bangkok, Thailand, and we discuss an extension of the original model to accommodate interval censoring arising due to the study design. PMID- 11764266 TI - A multiple imputation approach to regression analysis for doubly censored data with application to AIDS studies. AB - Sun, Liao, and Pagano (1999) proposed an interesting estimating equation approach to Cox regression with doubly censored data. Here we point out that a modification of their proposal leads to a multiple imputation approach, where the double censoring is reduced to single censoring by imputing for the censored initiating times. For each imputed data set one can take advantage of many existing techniques and software for singly censored data. Under the general framework of multiple imputation, the proposed method is simple to implement and can accommodate modeling issues such as model checking, which has not been adequately discussed previously in the literature for doubly censored data. Here we illustrate our method with an application to a formal goodness-of-fit test and a graphical check for the proportional hazards model for doubly censored data. We reanalyze a well-known AIDS data set. PMID- 11764267 TI - Partial knowledge and answer-until-correct tasks in birds and humans. AB - Jolliffe and Jolliffe (1997, Biometrics 53, 1136-1142) and Ridout (1999, Biometrics 55, 660-662) have proposed models applicable to memory in coal tits. It is now argued that the birds' task is analogous to answer-until-correct tests used in educational settings in humans, and models from the latter context may be used with the birds' data. PMID- 11764268 TI - On the first-order Rao-Scott correction of the Umesh-Loughin-Scherer statistic. AB - Decady and Thomas (2000, Biometrics 56, 893-896) propose a first-order corrected Umesh-Loughin-Scherer statistic to test for association in an r x c contingency table with multiple column responses. Agresti and Liu (1999, Biometrics 55, 936 943) point out that such statistics are not invariant to the arbitrary designation of a zero or one to a positive response. This paper shows that, in addition, the proposed testing procedure does not hold the correct size when there are strong pairwise associations between responses. PMID- 11764269 TI - Parameterization of multivariate random effects models for categorical data. AB - Alternative parameterizations and problems of identification and estimation of multivariate random effects models for categorical responses are investigated. The issues are illustrated in the context of the multivariate binomial logit normal (BLN) model introduced by Coull and Agresti (2000, Biometrics 56, 73-80). We demonstrate that the BLN model is poorly identified unless proper restrictions are imposed on the parameters. Moreover, estimation of BLN models is unduly computationally complex. In the first application considered by Coull and Agresti, an identification problem results in highly unstable, highly correlated parameter estimates and large standard errors. A probit-normal version of the specified BLN model is demonstrated to be underidentified, whereas the BLN model is empirically underidentified. Identification can be achieved by constraining one of the parameters. We show that a one-factor probit model is equivalent to the probit version of the specified BLN model and that a one-factor logit model is empirically equivalent to the BLN model. Estimation is greatly simplified by using a factor model. PMID- 11764270 TI - Covariate adjustment of event histories estimated from Markov chains: the additive approach. AB - Markov chain models are frequently used for studying event histories that include transitions between several states. An empirical transition matrix for nonhomogeneous Markov chains has previously been developed, including a detailed statistical theory based on counting processes and martingales. In this article, we show how to estimate transition probabilities dependent on covariates. This technique may, e.g., be used for making estimates of individual prognosis in epidemiological or clinical studies. The covariates are included through nonparametric additive models on the transition intensities of the Markov chain. The additive model allows for estimation of covariate-dependent transition intensities, and again a detailed theory exists based on counting processes. The martingale setting now allows for a very natural combination of the empirical transition matrix and the additive model, resulting in estimates that can be expressed as stochastic integrals, and hence their properties are easily evaluated. Two medical examples will be given. In the first example, we study how the lung cancer mortality of uranium miners depends on smoking and radon exposure. In the second example, we study how the probability of being in response depends on patient group and prophylactic treatment for leukemia patients who have had a bone marrow transplantation. A program in R and S-PLUS that can carry out the analyses described here has been developed and is freely available on the Internet. PMID- 11764271 TI - Legal issues and impact of restricted access and distribution. PMID- 11764272 TI - FDA perspective on risk management programs. PMID- 11764273 TI - The risk revolution: challenges and opportunities for pharmacists. PMID- 11764274 TI - New directions in the management of special risk medications. PMID- 11764275 TI - The risk revolution: an examination of the regulatory environment. PMID- 11764276 TI - Review: melanocyte migration and survival controlled by SCF/c-kit expression. AB - Melanocytes are derived from neural crest and migrate along the dorsolateral pathway to colonize the final destination in the skin. Stem cell factor and its receptor c-kit were identified as gene products of Sl and W mutant loci; both of them were known to have defects in melanocytes survival. In this review, we focus on the function of stem cell factor and c-kit in melanocyte migration and survival, which has become clearer in the last decade. By analysis of both molecules in wild-type and white spotting mutant mice, ligand and receptor set were shown to play multiple roles in the development of melanocytes in mouse ontogeny. Functional blockade of c-kit by specific monoclonal antibody illustrated distinct c-kit dependent and independent stages in melanocyte development. Finally, SCF transgene expression demonstrated that part of the c kit dependent step is regulated by spatiotemporally specific ligand expression and also indicated the presence of c-kit independent melanocyte stem cells in postnatal skin. PMID- 11764277 TI - Functional conservation of the promoter regions of vertebrate tyrosinase genes. AB - Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. Considering the important roles of pigments in the evolution and the adaptation of vertebrates, phylogenetic changes in the coding and flanking regulatory sequences of the tyrosinase gene are particularly intriguing. We have now cloned cDNA encoding tyrosinase from Japanese quail and snapping turtle. These nonmammalian cDNA are highly homologous to those of the mouse and human tyrosinases, whereas the 5' flanking sequences are far less conserved except for a few short sequence motifs. Nevertheless, we demonstrate that the 5' flanking sequences from the quail or turtle tyrosinase genes are capable of directing the expression of a fused mouse tyrosinase cDNA when introduced into cultured mouse albino melanocytes. This experimental method, which reveals the functional conservation of regulatory sequences in one cell type (the melanocyte), may be utilized to evaluate phylogenetic differences in mechanisms controlling specific gene expression in many other types of cells. We also provide evidence that the 5' flanking sequences from these nonmammalian genes are functional in vivo by producing transgenic mice. Phylogenetic changes of vertebrate tyrosinase promoters and the possible involvement of conserved sequence motifs in melanocyte-specific expression of tyrosinase are discussed. PMID- 11764279 TI - Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. AB - Catecholamines, including dopamine and norepinephrine, are the principal neurotransmitters that mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are implicated in some neurologic and neuropsychiatric disorders. Recent mouse molecular genetic approaches provide genetic evidence for an important role of catecholamines in brain functions. In this paper, I describe the phenotype of mutant mice with impairments in dopamine or norepinephrine biosynthesis. Mice defective in dopamine biosynthesis exhibit severe motor dysfunctions characterized by a reduction in spontaneous locomotion and cataleptic behavior, and defects in drug induced hyperactivity at the juvenile stage. They also exhibit defects in the acquisition of conditioned learning dependent on tone stimulus. These results indicate that dopamine is essential for motor control and emotional learning during postnatal development, possibly through nigrostriatal and mesolimbic neuronal pathways. On the other hand, mice carrying the mutation in the gene encoding tyrosine hydroxylase (the rate-limiting enzyme of catecholamine biosynthesis) display a reduction in norepinephrine biosynthesis. This leads to deficits in latent learning and long-term memory formation of different conditioned learning paradigms. The results indicate that norepinephrine is essential for the consolidation process of long-term memory, suggesting that norepinephrine may control the neuronal activity in the cerebral cortex or amygdala to maintain the memory process of conditioned learning. PMID- 11764278 TI - The role of phosphoinositide 3-kinase in the sorting and transport of newly synthesized tyrosinase-related protein-1 (TRP-1). AB - Tyrosinase-related protein-1 (TRP-1) is a 75 kDa type-1 transmembrane glycoprotein localized to the melanosome. The mechanism by which newly synthesized TRP-1 reaches its ultimate destination is currently unknown, but has been speculated to occur via the endosomal pathway. Recently, it has been shown that phosphatidylinositide (PI) 3-kinase is involved in various cellular functions, including regulating the constitutive movement of proteins from one intracellular compartment to another; however, whether PI 3-kinase participates in the trafficking of proteins such as TRP-1 to the melanosome is unknown. In this study we investigate the role of PI 3-kinase on the trafficking of TRP-1 in human melanoma MeWo cells using wortmannin, a potent inhibitor of PI 3-kinase. Our investigations demonstrate that wortmannin interferes with the membrane trafficking of TRP-1 in MeWo cells, and that it specifically results in the redistribution of the protein within a novel vesicular compartment with characteristics of the endosomal and lysosomal compartments [positive for LAMP-1, and partially positive for CD63 and cation-independent mannose 6-phosphate receptors (CI-M6PR)], and is accessible to internalized proteins such as immunoglobulins. Movement within this novel compartment is microtubule and GTPase dependent. These findings have led us to postulate that TRP-1 is sorted from the trans-Golgi network to a compartment in the vicinity of late endosomes, trafficking from which to the melanosome appears to be dependent on PI 3-kinase as it is blocked by wortmannin. PMID- 11764280 TI - Evidence for distinct membrane traffic pathways to melanosomes and lysosomes in melanocytes. AB - We report here morphologic and biochemical evidence that melanosomes are distinct from lysosomes. Immunofluorescence analysis revealed that TRP-1, a melanosomal membrane protein, did not colocalize with lysosomal membrane proteins LAMP1 and LGP85 in melan-a cells. Wortmannin treatment of melanocytes enhanced the distinct compartmentalization of these melanosomal/lysosomal membrane proteins by the swelling of the endosomal-lysosomal systems. The heavily melanized melanosomes did not have an altered shape, which suggests a lesser degree of membrane dynamics of stage IV melanosomes. Terminal lysosomes loaded with TR-dextran are also distinct from melanosomes, thus indicating that melanosomes are isolated from the endocytic pathway that is a representative route to lysosomes. Because AP-3 mutation leads to mistargeting of both melanosome and lysosome membrane proteins, we propose that there is a late sorting step for melanosomes and lysosomes in melanocytes after AP-3 sorting. PMID- 11764281 TI - Endothelins are involved in regulating the proliferation and differentiation of mouse epidermal melanocytes in serum-free primary culture. AB - Mouse epidermal melanoblasts preferentially proliferated from disaggregated epidermal cell suspensions derived from newborn mouse skin in serum-free melanoblast-defined medium (MDM). After 14 d, almost all keratinocytes that existed predominantly in the early stage of primary culture died, and pure cultures of melanoblasts were obtained. Epidermal melanoblasts dramatically increased in number in MDMDF consisting of MDM supplemented with dibutyryl adenosine 3':5'-cyclic monophosphate (DBcAMP) and basic fibroblast growth factor (bFGF). Epidermal melanocytes increased in number in MDMD consisting of MDM supplemented with DBcAMP. On the other hand, epidermal melanocytes were induced to differentiate in MDMM consisting of MDM supplemented with alpha-melanocyte stimulating hormone (MSH). Pure cultured primary melanoblasts or melanocytes in MDMDF or MDMD were further cultured with MDMDF or MDMD supplemented with endothelin (ET)-1, -2, or -3 from 14 d. A dramatic increase in the number of melanoblasts or melanocytes was observed after 7 d; however, no increase in the number of melanoblasts or melanocytes was observed in the absence of ET-1, -2, or -3. The increase in the number of melanoblasts or melanocytes was comparable with that of melanoblasts or melanocytes cocultured with secondary keratinocytes in MDMDF or MDMD. Also, pure cultured primary melanoblasts in MDM were further cultured with MDMM supplemented with ET-1, -2, or -3 from 14 d. A dramatic increase in the percentage of melanocytes in the melanoblast-melanocyte population was observed after 7 d; however, no increase in the percentage of melanocytes was observed in the absence of ET-1, -2, or -3. The increase was comparable with that of melanocytes cocultured with secondary keratinocytes in MDMM. Moreover, anti-ET-1, -2, and -3 antibodies inhibited both the proliferation of melanoblasts or melanocytes in MDMDF or MDMD and the differentiation of melanocytes in MDMM in primary culture. These results suggest that ET-1, -2, and 3 are one member of the keratinocyte-derived factors that are involved in regulating the proliferation and differentiation of mouse epidermal melanocytes in primary culture. PMID- 11764282 TI - The effect of thioredoxin on the expression of proopiomelanocortin-derived peptides, the melanocortin 1 receptor and cell survival of normal human keratinocytes. AB - An important constituent of the cellular antioxidant buffering system that controls the redox state of proteins is thioredoxin (TRX), a 13 kDa protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biologic functions similar to cytokines. We have previously reported that TRX released from UVB-irradiated keratinocytes stimulates melanogenesis by upregulating MSH receptor expression and its binding activity in melanocytes. The purpose of this study was to examine the effects of TRX on keratinocytes as an autocrine factor. TRX suppressed the UVB-induced production and secretion of alpha-melanocyte stimulating hormone (alpha-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocytes; however, TRX upregulated melanocortin 1 receptor (MC1-R) expression synergistically with UVB in normal human keratinocytes. These results suggest that exogenous TRX regulates expression of those genes in different manners. Furthermore, addition of an antibody against TRX induced cell death in keratinocytes, probably due to enhanced signaling of MSH, as it has been shown that MSH suppresses heat shock protein (hsp) 70 expression in differentiated keratinocytes, which express high levels of MC1-R and decreases their survival rate during oxidative stress. Taken together, the results suggest that keratinocyte-derived TRX regulates the expression of stress inducible neuropeptides and their receptor, and is critically involved in the survival of keratinocytes. PMID- 11764283 TI - Histologic study of the regeneration process of human hair follicles grafted onto SCID mice after bulb amputation. AB - This study examines histologically the degeneration and subsequent regeneration processes of human hair follicles whose bulb is severely damaged. Human scalp hair follicles were isolated and grafted onto immunodeficient mice after their bulb was amputated. On day 14, thickening and corrugation of the vitreous membrane, apoptosis of follicular keratinocytes, and regression of the lower portion of the follicles were observed. By day 20, mesenchymal cells had accumulated around the lower end of the follicles. From day 14 through 50, the follicular regression and apoptosis continued, and between days 30 and 40 the follicles became maximally shortened, and the vitreous membrane disappeared. By day 50 the lower end of the follicles had become cup-shaped, and the cup surrounded an aggregate of mesenchymal cells that corresponded to the dermal papilla. By day 60, all the grafted follicles had developed into anagen VI follicles, and the apoptosis had ceased. These results indicate that human scalp hair follicles whose bulb is completely destroyed enter into dystrophic telogen after restoration of the dermal papilla, then into anagen, and that the duration of the dystrophic telogen is shorter than that of the normal hair cycle. PMID- 11764284 TI - Tissue regeneration: hair follicle as a model. AB - The Cre-loxP strategy has allowed us to generate the mice whose keratinocytes are devoid of Stat3, which play a pivotal role in the signal transduction following the stimulation with various growth factors/cytokines, such as EGF, HGF, or IL-6. Although keratinocyte-specific Stat3-disrupted mice were born normal with intact skin and the first hair cycle, they exhibited retardation of wound healing and absence of the second hair cycle onward, leading to development of spontaneous skin ulcers and alopecia as they aged. Thus, analyses of these mice reveal that Stat3 in keratinocytes contributes to the regeneration of epidermis and hair cycle process. PMID- 11764285 TI - Histochemical and immunohistochemical markers for human eccrine and apocrine sweat glands: an aid for histopathologic differentiation of sweat gland tumors. AB - Apocrine and eccrine sweat glands are distinct in function, although they are closely related to each other developmentally and morphologically. In certain sweat gland tumors, it is difficult to differentiate between eccrine or apocrine sweat glands. Therefore, this paper reviews histochemical and immunohistochemical markers to differentiate apocrine and eccrine sweat glands with the aim of better understanding the structural and functional characteristics of these sweat glands. Specific markers for apocrine sweat glands are as follows: neuraminidase sensitive anionic sites detected by cationic colloidal gold at pH 2.0, and mitochondrion-like secretory granules that have epidermal growth factor-like antigenicity. The following antibodies react with apocrine sweat glands but not with eccrine sweat glands; the antibodies raised against 70 kDa glycoprotein purified from human milk fat globule membranes, and HMFG-1 (1.10.F3) monoclonal antibody produced by immunizing mice with defatted human milk fat globule membranes. Markers for eccrine sweat glands are as follows: dark cell granules that have chondroitinase ABC sensitive anionic sites detected by cationic gold at pH 2.0 after pretreatment with EGTA, and intercellular canaliculi with high activity of alkaline phosphatase. CEA and GCDFP-15 are expressed in both eccrine and apocrine sweat glands. Anti-EMA monoclonal antibody (E29) stains both eccrine and apocrine sweat glands. PMID- 11764286 TI - Expression of opsin molecule in cultured murine melanocyte. AB - Recently, we demonstrated the expression of rhodopsin in the tail fin of the Xenopus tadpole, in which photosensitive melanophores exist (Miyashita et al, The photoreceptor molecules in Xenopus tadpole tail fin, in which melanophores exist. Zool Sci 18:671-674, 2001). The presence of opsin molecules in pigment cells of lower vertebrates raises the possibility that pigment cells in animal skin function as photosensors generally. To explore this possibility in higher vertebrates, we tried to detect photoreception molecules in mammalian melanocytes. We extracted total RNA from Melan a2, a cell line of immortal murine melanocyte, which is derived from C57BL mice. The DNA sequence obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was homologous to the corresponding portion of the sequence of ocular rhodopsin of mice. Western blotting and fluorescent immunocytochemistry showed the existence of the opsin protein in the melanocytes. Another cell line, EL4, which is derived from lymphoma of C57BL/6N, scarcely expresses opsin mRNA, as judged by RT-PCR. Thus expression of the opsin gene is not ubiquitous among immortal cell lines. Detection of rhodopsin mRNA in murine tissues of C57BL/6N by RT-PCR showed its presence in the eye and skin but not in the liver. The role of the opsin molecule in melanocyte is not known at present, but this will provide additional insight into photoreception systems in animal skin. PMID- 11764287 TI - Photobiologic and photoimmunologic characteristics of XPA gene-deficient mice. AB - Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Just like human XP patients, homozygous (-/-) mice developed stronger longer-lasting acute inflammation than did wild-type mice after a single irradiation with UVB. Moreover, the model mice showed more severe UV-induced damage of keratinocytes and Langerhans cells than did the control mice. UVB-induced local and systemic immunosuppression was greatly enhanced in the (-/-) mice. Treatment with indomethacin, an inhibitor of prostaglandin (PG) synthesis, inhibited UV-induced inflammation and abrogated immunosuppression. In XPA-deficient mice, the amount of PGE2 and the expression level of COX-2 mRNA greatly increased after UVB irradiation compared with wild-type mice. These results suggest that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation induce COX 2 expression and subsequently produce a high amount of PGE2, which causes the enhancement of inflammation and immunosuppression. In XPA-deficient mice, the natural killer cell activity significantly decreased after repeated exposures to UVB. Our experimental data indicate that cancer development in XP patients involves not only mutagenesis due to the defect in DNA repair, but also the enhanced UV-immunosuppression and intensified impairment of natural killer function. PMID- 11764288 TI - Review: ligands for receptor tyrosine kinases expressed in the skin as environmental factors for melanocyte development. AB - Skin is the major tissue where melanocytes develop, and skin keratinocytes provide the necessary micro-environment for melanocyte survival, proliferation, differentiation, and migration. In this paper, we will discuss the ligands for receptor tyrosine kinases produced as environmental cues to support melanocyte development in the skin. PMID- 11764289 TI - Ultraviolet B irradiation induces apoptosis of keratinocytes by direct activation of Fas antigen. AB - Ultraviolet B (UVB) irradiation induces apoptosis of keratinocytes, where p53 has been suggested to play an important role. Recently we have shown that UVB irradiation induces apoptosis of SV40-transformed human keratinocytes (SVHK cells). Because p53 function is impaired in SVHK cells by large T antigen, a UVB induced p53-independent apoptotic pathway was suggested. We investigated the UVB induced apoptotic pathway using various keratinocytes. Cultured mouse keratinocytes of homozygous p53 deficient mice (p53(-/-)) were markedly resistant to UVB-induced apoptosis compared with keratinocytes from wild or heterozygous p53 deficient mice (p53(-/+)). Twenty per cent of keratinocytes derived from p53 (-/-) mice, however, induced apoptosis following UVB irradiation. Analysis using caspase inhibitors disclosed activation of caspase 8 and 3 in UVB-irradiated SVHK cells. Keratinocytes derived from MRL/lpr mice, which have mutated Fas antigen, showed diminished UVB-induced apoptosis suggesting that Fas antigen is significantly involved in UVB-induced apoptosis. Immunohistochemical analysis revealed that UVB irradiation induces aggregation of Fas antigen showing a dense dot-like staining, which was also observed in SVHK cells treated with agonistic anti-Fas antibody, CH11. Pretreatment of antagonistic anti-Fas antibody, ZB4, inhibited CH11-induced but not UVB-induced multimerization of Fas antigen. Furthemore, UVB irradiation did not affect the basal expression of Fas ligand mRNA, protein and soluble Fas ligand. These results indicate that UVB irradiation induces multimerization of Fas antigen that results in apoptosis without the Fas ligand. PMID- 11764290 TI - Both of the N-terminal and C-terminal regions of human papillomavirus type 16 E7 are essential for immortalization of primary rat cells. AB - E7 oncoproteins of mucosal high-risk human papillomavirus type 16 and 18 (HPV16 and HPV18) immortalize primary rodent cells and transform them in collaboration with the activated ras, possibly by interaction with retinoblastoma gene product RB and its related p107. On the other hand, E7 of the cutaneous epidermodysplasia verruciformis-associated HPV5 and HPV8 possess ras-collaborative transformation but not immortalization activity. By using polymerase chain reaction, we constructed chimeric E7 from immortalizing HPV16 E7 and nonimmortalizing HPV5 E7, which have boundaries at the 37/39th, 61/62th, or 79th codon of the HPV16 E7. These chimeric E7 were cloned into the expression vectors to examine their ras collaboration and immortalization activities. Chimeric E7 that contained N terminal 39 amino acid residues (R), 61R and 79R of HPV16 E7, showed ras collaboration activity in primary rat embryo fibroblast and primary baby rat kidney (BRK) cells as efficiently as HPV16 E7. Meanwhile, only the chimeric E7 containing N-terminal 79R of HPV16 E7 was able to immortalize primary BRK cells without second oncogenes. Co-transfection of two chimeric E7 carrying HPV16 N terminus and HPV16 C-terminus induced immortalization of primary BRK cells. These results suggest that (i) in addition to the N-terminal RB-binding domain, the C terminal region of HPV16 E7 is essential for immortalization of primary BRK cells, and (ii) two different immortalization functions are present in the two regions of HPV16 E7. By using a yeast two hybrid system, we searched for the HeLa cDNA whose products can bind the C-terminal region of HPV16 E7. PMID- 11764291 TI - Immunologic characterization of HIV-specific DNA vaccine. AB - We developed a method for applying HIV-1 DNA vaccine topically in mice. Topical application of DNA vaccine to the skin is useful against infections. To find a less expensive and less cumbersome vaccination method, we administered HIV-1 DNA vaccine to the skin of mice after elimination of keratinocytes using a fast acting adhesive. HIV-1 DNA vaccine induced high levels of both humoral and cell mediated immune activity against HIV-1 envelope antigen. A high level of HIV-1 specific cytotoxic T lymphocyte response was also observed, and a high level of IFN-gamma and IL-4 production was induced by the improved skin application of DNA vaccine. High levels of both HIV-specific cytotoxic T lymphocyte and delayed type hypersensitivity in topical application were induced by coadministration of the DNA vaccine with IL-12 expression plasmids and granulocyte-macrophage colony stimulating factor expression plasmids. These immune responses were inhibited by intradermal injection of anti-CD11c or anti-I-A/I-E antibody. Therefore, topical administration of DNA vaccine is an effective route, and may be very useful for the prevention of infectious diseases. PMID- 11764292 TI - Stress response, tachykinin, and cutaneous inflammation. AB - In the last decade, several new aspects of glucocorticoid (GC)-actions on immune cells have been recognized. This recognition has been largely obtained through clinical observations of stress-induced exacerbations of certain dermatologic diseases. To clarify whether GC modulates cutaneous inflammatory reactions besides its known anti-inflammatory effect, first we examined the effect of long term application of topical GC on several kinds of inflammatory responses induced in the murine model and demonstrated that these regimens significantly augmented the classical contact sensitivity reaction, the croton oil-induced irritant reaction, and the IgE-mediated biphasic cutaneous reaction. In addition, large dose topical steroid and its withdrawal enhanced scratching behavior in hapten challenged mice. This augmented scratching behavior correlated with the induction of preprotachykinin mRNA expression in the challenged skin. In an in vitro experiment, a low-dose, stress-induced level of glucocorticoid significantly upregulated hapten-induced proinflammatory cytokine (IL1alpha) production by murine keratinocyte cell line Pam 212 and induced substance P peptide production from cultured human keratinocytes. Our results suggest that unsuitable use of GC in addition to stress-induced GC may modulate immune function in the skin through aberrant production of tachykinin, such as substance P or other epidermal cell derived cytokines. PMID- 11764293 TI - Environmental effects on the functions of the stratum corneum. AB - The stratum corneum (SC) is such an efficient barrier that only 2-5 g per h per cm2 of transepidermal water loss (TEWL) occurs in normal skin. The SC also plays another important role at the skin surface in keeping our skin smooth and flexible by binding water. We exposed a simulation model of in vivo SC to various, excessive physical insults in vitro, such as irradiation with 1 J per cm2 of UVB, 50 J per cm2 of UVA, or 3000 rad of X-ray, heating at 90 degrees C for 3 min, freezing at -196 degrees C for 60 s or repeated placement in an extremely dry or humid condition. None of them could cause any permanent change in the SC functions. Only the application of chemical agents such as lipid solvents or a detergent or the affliction of trauma resulted in a functional derangement of the SC. Because the viable skin tissues are more vulnerable to the effects of the environment than the SC, most of the abnormalities of the SC functions developing after environmental insults are secondarily caused by enhanced epidermal proliferation induced under the influence of underlying inflammation. These functional abnormalities were found to be demonstrable with biophysical measurements long after the disappearance of skin redness, the clinically observable sign of inflammation. The SC abnormalities in inflamed skin are also detectable as a change in the content of chemical mediators. For example, the ratio between proinflammatory IL-1 and its receptor antagonist (IL 1ra) whose production by epidermal keratinocytes is markedly enhanced by various proinflammatory stimuli, showed a deviation towards an excess of the latter in inflammatory skin. Facial skin that is always exposed to the environment is unique in that its SC shows such a deviation in the IL-1/IL-1ra ratio suggestive for the presence of mild inflammation even in normal individuals. PMID- 11764294 TI - Cochlear melanocytes and MITF signaling. AB - Melanocytes occur not only in the skin and eyes but in the cochlea, where they exist as intermediate cells of the stria vascularis. Intermediate cells play an important role for cochlear function: Na+K+-ATPase and potassium channels of intermediate cells are essential for production of endocochlear potential and for preparation of ionic milieu in the stria. Consistent with this notion, melanocyte deficiency due to some gene disruptions results in hearing impairment in mice and humans. Mitf/MITF is essential for development and maturation of melanocytes, including strial intermediate cells. Disruption of MITF causes deafness, heterochromia irides, and leucodermia in Waardenburg syndrome type 2 individuals, whereas that of Mitf causes phenotypes of deafness, microphthalmia, and white coat in mice. Again, all of these phenotypes may be explained by a lack of melanocytes. Many signal transduction pathways target the Mitf/MITF gene or Mitf/MITF protein, and disruption of these pathways sometimes results in the phenotype similar to that caused by Mitf/MITF disruption. If not all, certainly many roads lead to MITF in melanocytes. PMID- 11764295 TI - Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation. AB - Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditory-pigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5' to 3' direction, each of which encodes the unique N-terminus of a given isoform. The 5' flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types. PMID- 11764296 TI - Definition, classification, and routine diagnosis of urticaria: a consensus report. AB - Urticaria is a well-known disease entity; however, with an increasing understanding of the molecular mechanisms involved in its pathogenesis, there is also growing evidence for a heterogeneity of urticaria. Currently it is sometimes difficult to compare divergent data reported by different centers researching urticaria due to a lack of precisely described patient populations. A consensus definition and classification of the disease and its subtypes, taking into account new developments, are therefore needed. In addition, this consensus report provides a guideline for diagnostic procedures in different subtypes of urticaria. PMID- 11764297 TI - Management of urticaria: a consensus report. AB - This consensus report is the result of a panel discussion during the International Clinically Oriented ESDR Symposium Urticaria 2000. Urticaria has a profound impact on the quality of life and effective treatment is required. The most important are nonsedating H1 antihistamines. They have been proven to be effective in double-blind controlled studies, but concentrations higher than those recommended may be necessary. Due to different urticaria subtypes and the individual variation in the course of the disease and response to treatment, however, alternative therapies may be required. Immunosuppressive drugs like cyclosporine A and corticosteroids should not be used long term due to undesirable side-effects. PMID- 11764298 TI - The role of allergens and pseudoallergens in urticaria. AB - Adverse reactions to food are a frequently discussed cause of urticaria. In acute urticaria 63% of patients suspect food as the eliciting factor; however, this cannot be confirmed in prospective studies. In adults the rate of type I allergic reactions is below 1%, although in children the percentage appears to be higher. Also in chronic urticaria type I allergic reactions play only a minor role as an eliciting factor. The same holds for the physical urticarias. The role of pseudoallergic reactions has not been investigated for all types of urticaria, but apparently they are not important in physical urticarias; however, in acute urticaria pseudoallergic reactions against NSAID are responsible for approximately 9% of cases, and in a subset of patients with chronic urticaria a diet low in pseudoallergens has been proven to be beneficial in several studies, with response rates observed in more than 55% of patients. Double-blind, placebo controlled challenge tests have shown that artificial food additives are not only to blame, with the majority of reactions being traced back to naturally occuring pseudoallergens in food. PMID- 11764299 TI - Pathomechanisms in physical urticaria. AB - Various exogenous stimuli, e.g., rubbing, pressure, cold, heat, or electromagnetic waves, have been described to elicit whealing reactions, the so called physical urticarias. They may occur as isolated diseases or in association with other types of urticaria. In many cases, the respective physical factors can be defined exactly, e.g., the degree of temperature changes or the range of eliciting ultraviolet wavelengths. In contrast, the underlying pathomechanisms are mostly still obscure. In the past, often contradictory results have been reported regarding the role of IgE, complement factors, histamine, or even mast cells. Recently, many investigations have been performed on solar urticaria where subgroups of patients with different clinical and pathophysiologic features could be defined and mechanisms of tolerance induction have been studied that also offered an efficient treatment modality. Therefore this review will mainly focus on this type of disease as a paradigm of the pathomechanisms of physical urticaria. PMID- 11764300 TI - Adhesion molecules and cellular infiltrate: histology of urticaria. AB - Urticarial reactions are characterized by dermal capillary dilatation and edema, associated with a variably intense mixed inflammatory infiltrate consisting of neutrophils, eosinophils, T-helper lymphocytes, and activated macrophages. Mast cell numbers are moderately increased by a factor of 2.4, in contrast to mastocytosis where numbers are much higher (5-48-fold increase). In urticarial vasculitis there is in addition endothelial damage, leukocytoclasia, and fibrin and complement deposition. The emigration of leukocytes is regulated by vasoactive and chemotactic mediators released firom mast cells, inducing a sequential upregulation of endothelial adhesion molecules (P-selectin, E selectin, ICAM-1, and VCAM-1), of beta2-integrins on leukocytes, and of cytokines on endothelial, epithelial, and infiltrating cells. In nonlesional skin, there is also an increase of mast cells and an upregulation of endothelial adhesion molecules, probably due to molecules in the circulation of which P-selectin and TNFalpha have so far been demonstrated. Whereas these data provide a molecular basis for the understanding of variations in mast cell-dependent pathology, they underline the fact that they are not diagnostic for different types of urticaria, except for urticarial vasculitis and mastocytosis. PMID- 11764301 TI - Basophils in chronic urticaria. AB - Blood basophils are reduced in chronic urticaria and respond less well to immunologic stimuli. Active recruitment of basophils from peripheral blood into lesional skin may be important in wheal pathogenesis. PMID- 11764302 TI - Cold urticaria. AB - Cold urticaria is one form of urticaria that may be associated with other forms of physical urticarias. Frequency is generally estimated at two or three per 100. The triggering effect of cold is found at history taking in most of the cases. The urticaria is usually superficial, and more rarely associated with deep and/or mucosal urticaria. The diagnosis is based on history taking and the ice cube test. An exhaustive search for an etiologic factor is often unfruitful, and the presence of a cryopathy should lead to a complete work-up. Therapy of cold urticaria may prove to be difficult. In patients with secondary cold urticaria, underlying disease must be treated in order to resolve the skin symptoms. H1 antihistamines can be used but the clinical responses are highly variable. Short time treatment with low concentration corticosteroids suppresses the symptoms only partially and temporarily. In patients who do not respond to previous treatments, induction of cold tolerance may be proposed but the procedure is difficult to carry out in daily life over an extended period. Key word: cryoglobulins. PMID- 11764303 TI - Mastocytosis: review of clinical and experimental aspects. AB - Mastcytosis is a rare disease characterized by an abnormal increase of mast cells in tissues. The skin is the organ most frequently involved, but mast cells also accumulate in the bone marrow, gastrointestinal tract, lymph nodes, spleen, and liver. Recent studies suggest that activating mutations of c-kit, a protooncogene encoding for the receptor (kit) of stem cell factor, are a possible cause of some forms of mastocytosis. In addition, an increased rate of chromosomal aberrations has been found. Despite significant advances in research on mastocytosis, curative treatment is not yet available. Current management is based on avoidance of mediator-releasing triggers and symptomatic treatment. PMID- 11764304 TI - Delayed pressure urticaria. AB - Delayed pressure urticaria is a physical urticaria where erythematous, often painful swellings occur at sites of sustained pressure on the skin, after a delay of several hours. If sought, it is present in up to 40% of patients with ordinary chronic "idiopathic urticaria" to a varying degree. Compared with other urticarias, the pressure-induced lesions impair the quality of life of patients most severely. The pathogenesis is not well characterized, but whealing is dependent on mast cell activation, with the histology of lesions also showing a deep dermal inflammatory infiltrate of neutrophils and eosinophils, without vasculitis. Treatment of delayed pressure is generally unsatisfactory, and is often resistant to antihistamine and a range of anti-inflammatory medication. Oral steroids, although the most effective therapy, are unsuitable for long-term use. Delayed pressure urticaria may persist for many years, and improved or novel methods of management are under investigation. PMID- 11764305 TI - Conditional autoantibodies in urticaria patients: a unifying hypothesis. AB - Chronic urticaria may be characterized by conditional autoantibodies against the alpha-chain of the high-affinity receptor for IgE (FcepsilonRI). These autoantibodies are termed conditional as they only recognize unoccupied FcepsilonRI. The same conditional reactivity pattern has also been found in sera of atopic and normal healthy donors. Any condition resulting in accessibility of FcepsilonRI will render these autoantibodies anaphylactogenic. This finding offers a unifying hypothesis for the manifestation of different forms of urticaria. Non-immunologic triggers may thereby influence directly or indirectly the number of accessible FcepsilonRI allowing the conditional autoantibodies to induce urticaria symptoms. PMID- 11764306 TI - Standard treatment: the role of antihistamines. AB - Histamine-1 (H1) antihistamines are the first-line drug for the treatment of urticaria. Major progress has been achieved in recent years both in the understanding of their ligands, the H1-histamine receptors, and therefore in the mechanisms of their pharmacologic effects, as well as in the development of safer antihistamines with low or no sedating effects and no interactions on the level of potassium channels leading to QT-prolongations and interactions on the level of cytochrome P450 isoenzymes. This development has brought antihistamines very close to the ideal antihistamines that are desired by clinicians to treat most types of urticaria in patients who have to take these drugs for a long time. PMID- 11764307 TI - Alternative treatments for severely affected patients with urticaria. AB - A none sedating antihistamine is the treatment of choice for most patients with urticaria. There are, however, several occasions where alternative treatments are appropriate. In this paper these alternative treatments of various types of urticaria are discussed. The treatment of anaphylactic shock where urticaria often is the first sign is also discussed. In all types of urticaria it is important to work with the patient and try to eradicate the cause or inhibit the mediators giving the clinical signs. PMID- 11764308 TI - Territoriality and obsessive-compulsive symptoms. AB - We proposed a relationship between territoriality and obsessive-compulsive (OC) symptoms and derived and tested several hypotheses. We predicted that territoriality could be adequately assessed by a new self-report measure, that a nonspurious and significant relationship exists between territoriality and OC symptoms and disorder, that territoriality would serve as a risk for the future increase of OC symptoms, and that OC disorder (OCD) patients would manifest their territoriality needs by choosing to sit farther from their therapists than non OCD patients. Results from four studies on nonpatient and patient samples were consistent with our preliminary conceptualization, which deserves continued development and research attention. PMID- 11764309 TI - Fixity of belief, perceptual aberration, and magical ideation in obsessive compulsive disorder. AB - Clinicians and researchers have pondered the intersection of obsessive-compulsive disorder (OCD) and psychosis. We examined the records of 395 individuals seeking treatment for OCD and classified participants according to their most frequent or distressing obsession and compulsion. All participants completed measures of fixity of belief, perceptual distortions, magical ideation, and psychotic symptoms. Results indicated that individuals who reported fear of harming self or others via overwhelming impulse or by mistake, and those with religious obsessions, had poorer insight and more perceptual distortions and magical ideation than did individuals with other types of obsessions. These results did not appear to reflect mere differences in OCD severity. Results are discussed in light of previous findings showing that psychotic-like symptoms are associated with attenuated treatment outcome in OCD. More research is needed to assess the absolute magnitude of psychotic-like features in OCD patients with impulse/mistake and religious obsessions and to examine whether these features interfere with standard cognitive-behavioral therapy. PMID- 11764310 TI - Prediction of anxiety disorders using the state-trait anxiety inventory for multiethnic adolescents. AB - The purpose of this study was to determine the validity of the State-Trait Anxiety Inventory (STAI) in predicting DSM-III-R anxiety disorders based on the Diagnostic Interview Schedule for Children (DISC, Version 2.3) and using Asian/Pacific Islander adolescents. An overall prevalence rate of 9.19% for generalized anxiety disorder, overanxious disorder, or social phobia was consistent with past studies. As hypothesized, STAI negatively worded (i.e., Factor 2) items were better predictors than positively stated (i.e., Factor 1) items. The STAI State mean was a better predictor of concurrent DISC anxiety disorders as compared to STAI State Factors I or 2. In contrast, the STAI Trait Factor 2 (negatively worded) composite was the best predictor for nonconcurrent DISC anxiety disorders as compared to STAI Trait Factor 1 or the overall STAI Trait subscale. Satisfactory predictive-validity values were obtained when using the STAI State mean and Trait Factor 2 composite. Implications of these findings are discussed, including using the STAI as a screening measure for ethnically diverse adolescents. PMID- 11764311 TI - Heartbeat awareness and heart rate reactivity in anxiety sensitivity: a further investigation. AB - We examined the effects of anxiety sensitivity (AS) and arousal induction on heartbeat awareness and heart rate reactivity in a nonclinical undergraduate sample. Students were randomly selected from a larger screening sample to fill two groups (high and low AS; n = 15 per group) based on Anxiety Sensitivity Index (ASI) [Peterson, R. A., & Reiss, S. (1992). Anxiety Sensitivity Index manual (2nd ed. revised). Worthington, OH: International Diagnostic Systems] scores. Participants completed a mental arithmetic/spelling task to induce arousal. At two phases (i.e., baseline vs. stress), participants estimated their heart rates during specified intervals using a mental tracking paradigm. Actual heart rates were simultaneously measured. Although heart rate did increase significantly from baseline to stress phases, high and low AS groups did not differ in terms of heart rate reactivity to the stressor. As hypothesized, high AS individuals were more accurate in estimating their actual heart rate as compared to low AS individuals. Contrary to hypothesis, the AS group differences in accuracy of heartbeat estimations did not vary across baseline vs. stress phases. Interestingly, only low AS individuals provided heart rate estimates which were significantly lower than their actual heart rate readings. Although high and low AS individuals did not differ in actual heart rate, high AS individuals provided significantly higher heart rate estimates than low AS individuals. These results are consistent with the interoceptive sensitivity hypothesis. Implications of the greater heartbeat awareness of high AS individuals are discussed. PMID- 11764312 TI - Parental bonding and anxiety: differences between African American and European American college students. AB - Empirical evidence suggests that early home environments characterized by low care and high overprotection are positively associated with the adult expression of anxiety. While available evidence supports this position for European Americans, there has been no examination of the relationship between perceived parental rearing practices and anxiety among African Americans despite the theoretical assertion that African American parenting environments may be characterized as somewhat more overprotective than European Americans. This study investigated the relationship between maternal rearing patterns and trait and state measures of anxiety and depression among a sample of 59 African American and 55 European American college students. Results indicated that both groups reported similar levels of anxiety, depression, perceived care, and perceived overprotection. European Americans exhibited the typical pattern of a negative relationship between anxiety, depression, and care and a positive relationship between anxiety and overprotection. African Americans evidenced a similar negative relationship between anxiety, depression, and care, but no relationship between anxiety, depression, and overprotection. Furthermore, specific aspects of ethnic identity (i.e., ethnic achievement, ethnic behaviors) were found to be negatively associated with measures of trait anxiety among African Americans but not European Americans. PMID- 11764313 TI - Noninvasive electrical imaging of the heart: theory and model development. AB - The aim of this work is to begin quantifying the performance of a recently developed activation imaging algorithm of Huiskamp and Greensite [IEEE Trans. Biomed. Eng. 44:433-446]. We present here the modeling and computational issues associated with this process. First, we present a practical construction of the appropriate transfer matrix relating an activation sequence to body surface potentials from a general boundary value problem point of view. This approach makes explicit the role of different Green's functions and elucidates features (such as the anisotropic versus isotropic distinction) not readily apparent from alternative formulations. A new analytic solution is then developed to test the numerical implementation associated with the transfer matrix formulation presented here and convergence results for both potentials and normal currents are given. Next, details of the construction of a generic porcine model using a nontraditional data-fitting procedure are presented. The computational performance of this model is carefully examined to obtain a mesh of an appropriate resolution to use in inverse calculations. Finally, as a test of the entire approach, we illustrate the activation inverse procedure by reconstructing a known activation sequence from simulated data. For the example presented, which involved two ectopic focii with large amounts of Gaussian noise (100 microV rms) present in the torso signals, the reconstructed activation sequence had a similarity index of 0.880 when compared to the input source. PMID- 11764314 TI - Computational framework for generating transport models from databases of microvascular anatomy. AB - Quantitative descriptions of transport and exchange in physiological systems should make use of the emerging wealth of data on vascular anatomic structure. These descriptions may take the form of computational models which then must be incorporated into the comprehensive database of knowledge of microcirculatory physiology being developed under the title, The Microcirculation Physiome Project. Toward this end we present a simple and efficient computational method for simulating transport (advection, permeation, diffusion) in tissues containing microvascular structures of arbitrary complexity. The method is convenient because transport is simulated on a regular Cartesian lattice, and efficient because features of the anatomy are resolved within individual volume elements of the lattice. As a result, relatively low-resolution lattices yield accurate results. Therefore the method provides a feasible approach for studying a general class of transport problems in the context of realistic representations of vascular anatomy. PMID- 11764315 TI - Importance of accurate geometry in the study of the total cavopulmonary connection: computational simulations and in vitro experiments. AB - Previous in vitro studies have shown that total cavopulmonary connection (TCPC) models incorporating offset between the vena cavae are energetically more efficient than those without offsets. In this study, the impact of reducing simplifying assumptions, thereby producing more physiologic models, was investigated by computational fluid dynamics (CFD) and particle flow visualization experiments. Two models were constructed based on angiography measurements. The first model retained planar arrangement of all vessels involved in the TCPC but incorporated physiologic vessel diameters. The second model consisted of constant-diameter vessels with non-planar vascular features. CFD and in vitro experiments were used to study flow patterns and energy losses within each model. Energy losses were determined using three methods: theoretical control volume, simplified control volume, and velocity gradient based dissipation. Results were compared to a simplified model control. Energy loss in the model with physiologically more accurate vessel diameters was 150% greater than the simplified model. The model with nonplanar features produced an asymmetric flow field with energy losses approximately 10% higher than simplified model losses. With the velocity gradient based dissipation technique, the map of energy dissipation was plotted revealing that most of the energy was dissipated near the pulmonary artery walls. PMID- 11764316 TI - Phase shifting prior to spatial filtering enhances optical recordings of cardiac action potential propagation. AB - Optical imaging of cardiac electrical activity using a voltage-sensitive dye provides high spatial resolution maps of action potential propagation and repolarization. Charge-coupled-device (CCD) camera-based imaging systems, however, are limited by their low signal-to-noise ratio. We have developed an image processing method to enhance the quality of optical signals recorded using a CCD camera. The method is based on the observation that within a small neighborhood of adjacent pixels, the morphology of the optical action potential varies little except for a phase shift in time resulting from the propagation of the wavefront. The method uses a phase-correlation technique to first correct for this time shift before spatially filtering with a 5 x 5 Gaussian convolution kernel (sigma = 1.179). A length 5 median filter is then applied to further reduce noise by filtering in the temporal domain. The image-processing scheme allows for more accurate extraction of maps of electrical activation, repolarization, and action potential duration. PMID- 11764317 TI - Extracellular measurement of anisotropic bidomain myocardial conductivities. I. Theoretical analysis. AB - The passive electrical properties of cardiac tissue, such as the intracellular and interstitial conductivities along the longitudinal and transverse axes, have not been often measured because intracellular electrodes are usually needed for these measurements. In this paper, we present a theoretical analysis of two myocardial models developed to estimate these properties by analyzing potentials recorded with a pair of extracellular electrodes while injecting alternating current between another pair of electrodes. First, the cardiac tissue is represented by a standard bidomain model which includes a membrane capacitance; second, this model is modified by adding an intracellular capacitance representing the intercalated disks. Numerical solutions are computed with a fast Fourier transform algorithm without constraining the anisotropy ratios of the interstitial and intracellular domains. We systematically investigate the effects of changes in the bidomain parameters on the voltage-to-current ratio curves. We also demonstrate how the bidomain parameters can be theoretically estimated by fitting, with a modified Shor's r algorithm, the simulated potentials along the longitudinal and transverse axes for different frequencies between 10 and 10,000 Hz. An important finding is that the interelectrode distance must be similar to the myocardial space constant so as to obtain frequency dependent measurements. PMID- 11764318 TI - Extraction and analysis of early ictal activity in subdural electroencephalogram. AB - Subdural electroencephalograms (SEEGs) are of great value in localizing primary epileptogenic regions in patients undergoing evaluation for focal resective epilepsy surgery. The data segments which contain a transition from interictal to ictal activity carry the most critical diagnostic information. Computer signal extraction within this transition period represents a challenging signal processing problem. In this work a two-step method is presented to extract early ictal activity. In the first step we employ a nonlinear signal decomposition technique in the wavelet domain to separate SEEG data into ictal and background components. In the second step we use time-frequency analysis and a novel integration algorithm to extract the desired information. Our experiments on clinically recorded data indicate that this method is highly effective allowing us to reveal important hidden features in the data which could not otherwise be observable. PMID- 11764319 TI - Type III units in the gerbil dorsal cochlear nucleus may be spectral notch detectors. AB - Broadband sounds originating in the median plane are thought to be localized by neural processing of spectral notches introduced by the filtering action of the pinnae. Previous studies (Nelken, I., and E. D. Young. J. Neurophysiol. 71:2446 2462, 1994: Spirou, G. A., and E. D. Young. ibid. 66: 1750-1768. 1991) suggested that type IV units in decerebrate cat dorsal cochlear nucleus (DCN) are functional detectors of these spectral notches. Intracellular marking studies by Ding et al. (Ding, J., T. E. Benson, and H. F. Voigt. J. Neurophysiol. 82:3434 3457, 1999) have shown that type III units in gerbil arise from the DCN's principal output neurons, which are thought to have type IV unit properties in cat. A relative paucity of type IV units in the decerebrate gerbil (Davis. K. A., J. Ding, T. E. Benson, and H. F. Voigt. J. Neurophysiol. 75: 1411-1431, 1996) has motivated this study of spectral notch sensitivity in the gerbil DCN. Responses to notch noise stimuli were recorded from 15 gerbil type III units to investigate whether these units may function as spectral notch detectors. For narrow notch noise stimuli, all 15 units showed excitatory responses. For progressively wider notches, the discharge rate of 13/15 units became inhibited. As the maximum limits of notch width were approached, 11/15 units showed some degree of recovery from this inhibition. This response pattern in gerbil type III units possesses the salient features of notch noise responses in cat type IV units and implicates type III units in gerbilline spectral notch detection processes. PMID- 11764320 TI - Real-Time linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells. AB - We describe a system for real-time control of biological and other experiments. This device, based around the Real-Time Linux operating system, was tested specifically in the context of dynamic clamping, a demanding real-time task in which a computational system mimics the effects of nonlinear membrane conductances in living cells. The system is fast enough to represent dozens of nonlinear conductances in real time at clock rates well above 10 kHz. Conductances can be represented in deterministic form, or more accurately as discrete collections of stochastically gating ion channels. Tests were performed using a variety of complex models of nonlinear membrane mechanisms in excitable cells, including simulations of spatially extended excitable structures, and multiple interacting cells. Only in extreme cases does the computational load interfere with high-speed "hard" real-time processing (i.e., real-time processing that never falters). Freely available on the worldwide web, this experimental control system combines good performance. immense flexibility, low cost, and reasonable ease of use. It is easily adapted to any task involving real-time control, and excels in particular for applications requiring complex control algorithms that must operate at speeds over 1 kHz. PMID- 11764321 TI - Nonlinear ligament viscoelasticity. AB - Ligaments display time-dependent behavior, characteristic of a viscoelastic solid, and are nonlinear in their stress-strain response. Recent experiments (25) reveal that stress relaxation proceeds more rapidly than creep in medial collateral ligaments, a fact not explained by linear viscoelastic theory but shown by Lakes and Vanderby (17) to be consistent with nonlinear theory. This study tests the following hypothesis: nonlinear viscoelasticity of ligament requires a description more general than the separable quasilinear viscoelasticity (QLV) formulation commonly used. The experimental test for this hypothesis involves performing both creep and relaxation studies at various loads and deformations below the damage threshold. Freshly harvested, rat medial collateral ligaments (MCLs) were used as a model. Results consistently show a nonlinear behavior in which the rate of creep is dependent upon stress level and the rate of relaxation is dependent upon strain level. Furthermore, relaxation proceeds faster than creep; consistent with the experimental observations of Thornton et al. (25) The above results from rat MCLs are not consistent with a separable QLV theory. Inclusion of these nonlinearities would require a more general formulation. PMID- 11764322 TI - Natural frequency analysis of periodontal conditions in human anterior teeth. AB - The purpose of this study was to evaluate the possibility of using natural frequency (NF) analysis to detect the attachment loss of periodontal tissue. In this study, 698 anterior teeth were examined by a conventional probing method and also by NF analysis. The teeth were triggered to vibrate with an impulse hammer, and the vibrational response was detected by an acoustic sensor. Our results demonstrate no significant difference in NF values between the upper-lower/left right quadrants of the tested teeth, although the mean natural frequency value of central incisors with periodontal disease was found to be 1.24 +/- 0.11 kHz which is significantly lower than that of teeth in a healthy condition (1.34 +/- 0.20kHz; p < 0.01). On the other hand, the mean frequency for periodontal disease involving canines (1.28 +/- 0.09 kHz) was also significantly lower than the corresponding value for healthy analogs (1.35 +/- 0.17 kHz; p < 0.05). These results suggest that NF analysis appears to be an effective method for assessing the periodontal condition of anterior teeth. Moreover, since this method is noninvasive, nondestructive, and necessitates minimal tooth contact, it can serve as an effective method for the early quantifiable testing and prevention of periodontal disease. PMID- 11764323 TI - A national payscale for veterinary nurses? PMID- 11764324 TI - Prediction of areas around the Mediterranean at risk of bluetongue by modelling the distribution of its vector using satellite imaging. AB - Bluetongue is an infectious disease of ruminants caused by a virus transmitted by biting midges, one species of which, Culicoides imicola, is the major vector in the Old World. Following an epizootic of African horse sickness,a related disease, in Iberia and Morocco between 1987 and 1991, C imicola was trapped for two years at 44 sites in the affected region and models were developed for predicting the abundance of C imicola at these sites. Discriminant analysis was applied to identify the best model of three levels of abundance from 40 Fourier processed remotely sensed variables and a digital elevation model. The best model correctly predicted the abundance level at 41 of the 44 sites. The single most important variable was the phase of the annual cycle of the normalised difference vegetation index. The model was used to predict the abundances of C imicola elsewhere around the Mediterranean and predicted high levels of abundance in many areas recently affected by bluetongue, including the Balearics, Sardinia, Sicily, eastern Greece, western Turkey, Tunisia and northern Algeria. The model suggests that eastern Spain, the island of Ibiza, the provinces of Lazio and Puglia in Italy, the Peloponnese and parts of northern Algeria and Libya may be at risk of bluetongue in 2001. PMID- 11764325 TI - Effect of selenium and vitamin E on antibody production by dairy cows vaccinated against Escherichia coli. AB - Sixty clinically healthy Holstein cows were randomly assigned to one of four groups according to their age and parity and vaccinated in late pregnancy (day 190) with a multivalent vaccine against Escherichia coli. The 15 cows in the first group (SeE) were injected intramuscularly with a solution of sodium selenite (0.1 mg Se/kg bodyweight) and vitamin E (alpha-tocopherol acetate, 8 U/kg bodyweight), the cows in the second group (Se) received only selenium and the cows in the third group (E) received only vitamin E at the same doses and by the same route of administration; the cows in the fourth group were used as controls. The vaccination and the injections of selenium and vitamin E were repeated 42 days later. The concentration of selenium in whole blood and of vitamin E in serum was determined by fluorometric methods. Specific antibody titres against E coli were determined in serum samples by ELISA. The results showed that the injection of selenium either alone or in combination with vitamin E significantly improved the production of specific antibodies against E coli, and that the production of specific antibodies was greater after the administration of selenium alone. PMID- 11764326 TI - Detection of antibodies to Borna disease virus in Turkish cats by using recombinant p40. AB - Recombinant p40 produced by baculovirus was used in an ELISA to screen samples of serum taken from 80 cats in Istanbul. The sera were also analysed for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Antibodies to Borna disease virus- (BDV) p40 were detected in 34 (42-5 per cent) of the 80 cats. Seventy-three per cent of the sera which were positive for FIV and 26 per cent of the sera which were negative for FIV had antibodies to BDV. There was no difference in the percentage of sera which were positive for BDV between the cats that were positive or negative for FeLV. Three of the cats had neurological disease and two of these had antibodies to BDV. Six sera with low, medium or high optical densities (ODS) by ELISA were analysed by Western blotting. Only the sera with medium and high ODS reacted specifically with p40 at a dilution of 1 in 1,000. PMID- 11764327 TI - Ceruminous otitis externa due to Demodex cati in a cat. PMID- 11764328 TI - Osteoarthritis of the elbow joint in adult sheep. PMID- 11764329 TI - Plasma glucocorticoid levels after pentobarbitone and thiopentone anaesthesia in New Zealand white rabbits. PMID- 11764330 TI - Prolapse of the soft palate in a male Arabian camel (Camelus dromidarius). PMID- 11764331 TI - Bluetongue around the Mediterranean in 2001. PMID- 11764332 TI - Complex vertebral malformation in a Holstein calf in the UK. PMID- 11764333 TI - Permethrin toxicity in cats following use of canine permethrin spot-on products. PMID- 11764334 TI - Orofacial pain syndrome in cats. PMID- 11764335 TI - EU requirement to survey for BSE in fallen stock: consequences for postmortem examination. PMID- 11764336 TI - Veterinary prescriptions for food animal medicines. PMID- 11764337 TI - Bare marketing. PMID- 11764338 TI - Hydroxyapatite femoral stems for total hip arthroplasty: 10- to 13-year followup. AB - Three hundred eighty hydroxyapatite-coated titanium alloy stems were implanted in a young and active patient population from 1987 through 1990. Within the population, 274 patients (314 hips) had a minimum 10-year and maximum 13-year followup. The average age of the population was 51 years. Thirty-seven percent of the population was 50 years or younger when operated on (average age, 39 years). Osteoarthritis was seen in 63.7% and avascular necrosis in 16.6% of patients. Fifty-four percent of patients were men. Clinically, these patients had early pain relief and rapid restoration of function. The Harris hip score averaged 92 points, and only 1.6% of patients had mild or moderate activity-related thigh pain. Radiographically, progressive remodeling occurred around the implants, 100% were bone stable, and no patient had endosteal distal osteolysis. Two patients had revision surgery for aseptic loosening: one at 2 years postoperative because of a nonunion of a concomitant subtrochanteric osteotomy and one at 9.5 years postoperative because of polyethylene wear and progressive osteolysis. The mechanical failure rate was 0.5%. The results show excellent lasting fixation of this tapered titanium alloy stem coated proximally with a thin, dense layer of hydroxyapatite. The stem has performed well in a young, active, high-risk population and in the hands of various surgeons. PMID- 11764339 TI - Tapered titanium cementless total hip replacements: a 10- to 13-year followup study. AB - The 10- to-13 year performance of 307 Mallory Head cementless tapered total hip replacements in 283 patients was assessed. Eighty-five percent of patients had a diagnosis of osteoarthritis. Fifty-one percent of patients were women. The mean patient age was 64 +/- 10 years. The Hex Loc cementless acetabular component and titanium alloy femoral heads were used in each patient. At final followup, 37 (13%) patients died, 32 (10%) had revision surgery, and two (1%) were lost to followup. No femoral stem was revised for aseptic loosening, but one was revised because of sepsis and one was revised because of a periprosthetic fracture. Wear, osteolysis, and loosening were problems with the Hex Loc cementless acetabular components and 31 (10%) acetabular components required revision because of these mechanisms. The mean Harris hip score at final followup of the remaining patients was 87 +/- 14 points. Three percent of these patients had thigh pain. Radiographic assessment revealed that no femoral stem or acetabular socket was definitely or probably loose. Three-dimensional wear assessment using the Devane technique was 0.35 mm per year. The Mallory Head cementless, tapered femoral component performed well in the patients in the current study, but unfortunately, the clinical results were compromised by the use of a suboptimal cementless acetabular component, the use of polyethylene that was gamma-irradiated in air, and by the use of titanium alloy femoral heads. Future developments obviously will be in the areas of better acetabular component design, alternate polyethylene sterilization methods, and enhancements of the femoral stem in terms of offset choices, neck design, and perhaps ingrowth surface. PMID- 11764340 TI - Total hip arthroplasty using two different cementless tapered stems. AB - The authors report their 15-year experience with primary total hip arthroplasty using collarless, tapered, porous-coated femoral stems (Trilock and Taperloc) in patients with osteoarthritis, rheumatoid arthritis, and in octogenarians. Excellent clinical results were achieved in all groups at latest followup. For the patients with Trilock stems, Taperloc stems, and patients who were octogenarians and patients with rheumatoid arthritis, Charnley pain scores were 5.6, 5.5, 5.7, and 5.7; Charnley function scores were 5.2, 5.1, 4.2, and 5.3; Harris hip scores were 92, 92, 82, and 93 points, respectively. There was a 2% rate of thigh pain with the Trilock, 4% with Taperloc, 4% in octogenarians, and 2% in patients with rheumatoid arthritis. In 96% of the patients in the Trilock group, in 100% of the patients in the Taperloc group, in 100% of the patients who were octogenarians, and in 100% of the patients with rheumatoid arthritis, femoral components showed radiographic evidence of bone ingrowth. There were six (12%) femoral component revisions in the Trilock group (all secondary to nonmodularity of the component at the time of acetabular revision), one femoral component revision in the Taperloc group and no femoral component revisions in the patients who were octogenarians or who had rheumatoid arthritis. Design features (collarless tapered wedge fit, circumferentially porous-coated) virtually ensure bone ingrowth and are thought to be responsible for the excellent clinical results and longevity. PMID- 11764341 TI - A low stiffness composite biologically fixed prosthesis. AB - The current authors addressed the question whether stress-induced adaptive bone remodeling of the proximal femur is a necessary consequence after total hip reconstruction with extensively biologically-fixed femoral components. A novel total hip femoral component was designed to simultaneously achieve stable skeletal fixation, structural durability, and reduced femoral stress shielding. This implant allowed for proximal and distal canal filling, yet was significantly less rigid than all-metallic femoral stems crafted of either cobalt chromium or titanium alloy. A cohort of 366 patients (386 hips) treated at 21 institutions worldwide now have been followed up a mean of 2.4 years postoperatively (range, 3 months-6 years). Two hundred sixty-eight patients have 2 years minimum followup. To date, no femoral implants have failed to achieve bone ingrowth and none have required revision. The implants appear radiographically well-fixed with no progressive radiolucencies or osteolysis. Radiostereometric analysis studies on one subset of patients showed stable initial fixation and minimal stem micromotion. Dual energy xray absorptiometry analysis on another subset of patients revealed excellent periprosthetic bone mineral density retention. Compared with more rigid metal implants, this design shows reduced proximal femoral bone loss secondary to stress-mediated bone resorption. PMID- 11764342 TI - Morphometric examination of straight, tapered titanium stems: a retrieval study. AB - Cementless straight, tapered rectangular cross section titanium stems have been used by the senior author since 1979. Thirty-four stems retrieved postmortem, after between 10 days and 15.2 years in situ, were studied morphometrically and histologically. Nineteen stems were first generation (1979-1986), with an incomplete sagittal taper and a mean surface roughness of 1 microm (Ra 1.23 +/- 0.3 microm); 15 stems were second generation after 1986, with a full biplane taper and a mean surface roughness of 4 microm (Ra 4.14 +/- 0.36 microm). Implant surface bony coverage was determined morphometrically in 10 segments of the stems, and expressed as a bone implant contact index. Histologically, there were no differences between implants with different levels of roughness. Morphometrically, the first-generation stems showed significant differences in coverage (distal > proximal); second-generation stems had a more uniform pattern. Stems retrieved early after arthroplasty had a mean bone implant contact index of 10%. The mean bone implant contact index showed attainment of maximum coverage by 5 years after arthroplasty, without additional apposition or loss thereafter. Patients younger than 65 years at arthroplasty had similar bone implant contact indices to patients 65 years or older; coverage in the six patients 80 years of age at retrieval did not differ from the rates in the other patients. Morphometry was able to provide objective evidence of design change effects. No differences in coverage were found in terms of times in situ, patient age at arthroplasty and at retrieval, and degree of stem surface roughness. PMID- 11764343 TI - Long-term results using the anatomic medullary locking hip prosthesis. AB - Since the introduction of cementless total hip arthroplasty in the early 1980s, concern has shifted from component loosening toward polyethylene wear and osteolysis. The current review of 223 consecutive unselected Anatomic Medullary Locking femoral and acetabular components extends the followup on a series of patients previously reported on at 5 and 10 years. The purposes are to describe the reasons for revisions and to assess the onset and size of osteolytic lesions, with the hypothesis that osteolysis represents an important cause of loosening. The population included 204 patients (211 hips) with mean followup of 13.9 years (range, 2-18 years). Among them, 122 patients (129 hips) had a minimum 15-year followup. Minimum 2-year radiographs with a mean radiographic followup of 12.2 years (range, 2-18 years) were available for 204 hips (197 patients). Of the entire study group, 39 hips (38 patients) had 44 component revisions, increasing the number of revisions by 24 since this series was reported previously. Twenty six patients (27 hips) had their first revision surgery more than 10 years after the primary surgery. The most common reason for revision of original components was wear or osteolysis occurring in 22 of the 39 hips (21 of 38 patients). The overall loosening rate was 3.4% (seven of 204) for femoral components and 5.4% (11 of 204) for acetabular components. Twenty-four percent of hips (48 of 204) had evidence of femoral or pelvic osteolytic lesions larger than 1.5 cm2. Femoral osteolysis was not associated with any case of femoral loosening, whereas seven of the 11 loose acetabular components were associated with pelvic lesions larger than 1.5 cm2. PMID- 11764344 TI - Fixation of the Quatroloc femoral component: a biomechanical and clinical study. AB - The current study was designed to test the hypothesis that press-fit femoral components with proximal press-fit and distal mechanical interlock can achieve fixation sufficient to allow bone ingrowth in osteoporotic and in normal bone. The addition of steps along the tapered distal stem improved fixation in osteoporotic bone enough to reduce micromotion to less than 20 microm in response to physiologic axial and torsional load. The clinical portion of the study included 226 consecutive hips (223 patients) with 2- to 4-year clinical results after total hip arthroplasty with a rectangular femoral component using proximal porous coating and distal mechanical interlock. Patient age ranged from 36 to 92 years. At 2 years postoperative, 4% of the patients with Type A (normal) femoral bone, 3% with Type B (intermediate) bone, and no patients with Type C (osteoporotic) bone had thigh pain. No clinical cases of loosening have occurred in normal or osteoporotic femurs. PMID- 11764345 TI - Prevention of dislocation after hip arthroplasty: lessons from long-term followup. AB - Regarding dislocation after total hip arthroplasty, prevention is worth an ounce of cure. The current authors evaluated dislocation after total hip arthroplasty during the 26-year practice of one surgeon to identify potential variables that can contribute to the prevention of dislocation. Between 1970 and 1996, dislocation after total hip replacement occurred after 7.2% of primary hip arthroplasty procedures (298 of 4164 primary hip replacements) and 11.2% of revision hip arthroplasty procedures (90 of 803 revision hip replacements). Significant findings included an increase in dislocation when 22-mm modular femoral heads were used and a decrease in dislocation after revision for dislocation when constrained liners were used. An additional finding was that 26% of first time dislocations occurred more than 2 years after surgery. Concerning prevention of dislocation, small head modular femoral components should be used cautiously, and constrained liners should be considered in complex revision cases. Patients should be counseled concerning the potential for dislocation many years after their arthroplasty. PMID- 11764346 TI - Effect of posterior capsular repair on early dislocation in primary total hip replacement. AB - Formal repair of the posterior capsule and short external rotator tendons has been described as a surgical approach to reduce the incidence of posterior dislocation after posterolateral surgical approach to primary total hip replacement. The purpose of the current study was to compare the incidence of early posterior dislocation (within the first 6 months after surgery) using a complete posterior capsulectomy versus a formal posterior capsular repair. In patients with a complete posterior capsulectomy, 52 of 1078 primary total hip replacements (4.8%) had an early posterior dislocation. In patients with posterior capsular repair, three of 437 primary total hip replacements (0.7%) had an early posterior dislocation. This difference was statistically significant. The only complication in the capsular repair group was an avulsion fracture of the greater trochanter in four of 437 total hip replacements (0.9%). PMID- 11764347 TI - Instability in primary total hip arthroplasty with the direct lateral approach. AB - Instability after a total hip arthroplasty is a serious complication. Dislocation rates as much as 6.5% after posterior approaches have been reported within the past decade. For this reason, the authors use the direct lateral approach for primary and revision total hip arthroplasties. A review of the arthroplasty database yielded 1515 primary total hip arthroplasties done via a direct lateral approach in 1333 patients. These arthroplasties were done within a 10-year period and patients with followup data less than 12 months were excluded. At the most recent examination, 11.6% of the patients had a moderate or severe limp and 2.5% had severe heterotopic ossification. Only six hips (0.4%) had a dislocation or episode of instability. Three patients had more than one dislocation and required revision surgery. The results of the current study show that dislocation after primary total hip arthroplasty almost can be eliminated using the direct lateral approach. The associated risks of heterotopic ossification or limp are acceptable. PMID- 11764348 TI - Component removal in revision total hip arthroplasty. AB - One of the primary steps in revision hip arthroplasty is the extraction of retained components before surgical reconstruction. In revision arthroplasty, the removal of well-fixed components and cement can be extremely demanding, time consuming, and damaging to the remaining host bone. The aims of the current study were to examine the numerous operative techniques used during extraction of acetabular and femoral components and review the results of revision hip arthroplasty after cementless component removal. A review of 157 acetabular components and 113 femoral components removed from 219 patients during hip revision arthroplasty between 1985 and 2000 was done. The average age of the patients was 64.3 years. The average followup was 5 years (range, 0.7-12.5 years). An extended proximal femoral osteotomy was done in 37 (33%) of the femoral revisions. There were 14 (5%) acetabular failures for which the patients required reoperation. There were no femoral rerevisions. Complications included dislocation (6% after acetabular revision and 9% after femoral revision), infection (6%), femoral fracture (6%), hematoma (3.5%), acetabular fixation failure (2.5%), and femoral osteolysis (1%). The removal of cemented and well fixed porous-coated implants can be done with adequate preoperative planning and a thorough knowledge of numerous implant removal techniques. PMID- 11764349 TI - Cementless femoral revision arthroplasty of the hip: minimum 5 years followup. AB - Durable fixation of the femoral component to the bone in femoral revision arthroplasty of the hip is the main ingredient to a successful reconstruction. Because of poor durability of cemented fixation in revision, in 1984, one author began to use cementless fixation with extensively porous-coated chrome cobalt stems. The current authors report the durability of that fixation technique in 137 hips (134 patients) followed up 5 to 16 years. With a mean followup of 9.3 years, 10 (7%) of the stems have been removed. Five (4%) were removed for fixation problems and five (4%) were removed for infection. Using the radiographic criteria of Engh et al, 83% of the stems achieved bony ingrowth. No late failure of fixation was observed. Canal-filling prostheses were more likely to have bone ingrowth as were stems placed in femurs with lesser degrees of bone stock deficiency. Significant thigh pain was seen in 7% of bone ingrown stems, 16% of stable fibrous fixated stems, and 75% of unstable stems. Significant thigh pain in bone ingrown stems was observed more commonly in osteoporotic femurs and bone stock deficient femurs. Severe stress shielding correlated with preoperative osteoporosis and larger diameter stems but has not caused failure. Excellent durability of this fixation technique is evident. PMID- 11764350 TI - Acetabular reconstruction with bone impaction grafting and a cemented cup: 20 years' experience. AB - Acetabular bone stock loss compromises the outcome in primary and revision total hip arthroplasty. In 1979, a biologic method was introduced with tightly impacted cancellous allografts in combination with a cemented polyethylene cup for acetabular reconstruction. With this technique, it is possible to replace the loss of bone and to repair normal hip mechanics and hip function with a standard implant. Based on the authors' 20 years experience, a review of the long-term data is presented in primary total hip arthroplasty with preexisting acetabular bone stock loss, primary total hip arthroplasty in rheumatoid arthritis, patients who had bone impaction when younger than 50 years, and in acetabular revisions. The survival rate with revision of the cup for aseptic loosening as the end point was 94% at 10 to 17 years, 90% at 10 to 18 years, 91% at 10 to 17 years, and 92% at 10 to 15 years. From biopsy specimens from humans and histologic data in animal experiments the incorporation of these impacted bone chips was proven. The acetabular bone impaction technique using large morselized bone chips (range, 0.7 1 cm) and a cemented cup is a reliable technique with favorable long-term outcome. PMID- 11764351 TI - Bridging massive acetabular defects with the triflange cup: 2- to 9-year results. AB - An unresolved issue in total hip arthroplasty is acetabular reconstruction when there is bone loss that results in pelvic discontinuity, that involves radiation compromised bone stock, or that is significant enough to exceed the limits of jumbo hemispherical cups. Achieving pain relief and initial and long-term implant stability on host bone are the major goals of this type of reconstruction. Seventy-eight hips in 76 patients in whom a large acetabular defect was bridged using a custom-designed, flanged component were reviewed retrospectively. The preoperative deficiency was classified as a combined deficiency in 39 hips and as a pelvic discontinuity in the other 39 hips. Six patients died before a minimum 2 years followup. With five patients considered lost to followup, there were 67 hips in 65 patients with an average followup of 53 months (range, 24-107 months). No Triflange Cup has been removed. Harris hip scores improved from a preoperative mean of 33.3 points to a postoperative mean of 82.1 points. Radiographically there are two patients with incompletely healed discontinuities but both are asymptomatic. Re-operation for recurrent dislocation occurred in six patients (7.8%). The Triflange Cup offers an alternative method of repair that reliably provides pain relief, initial implant stability, potential long-term implant stability, and pelvic stability in cases of discontinuity. PMID- 11764352 TI - Minimal medial epicondylectomy and decompression for cubital tunnel syndrome. AB - Sixty-four patients (66 elbows) treated for refractory cubital tunnel syndrome had minimal medial epicondylectomy and in situ decompression to minimize the potential disadvantages of classic medial epicondylectomy. After a mean followup of 27 months results were excellent in 27 patients (44%), good in 23 patients (35%), fair in 10 patients (15%), and poor in four patients (6%). No ulnar nerve palsy, ulnar nerve subluxation, or medial elbow instability were seen. The main complaint of patients regarding the procedure was tenderness at the osteotomy site. The results show that minimal medial epicondylectomy and in situ decompression of the ulnar nerve is a safe and effective method to treat patients with cubital tunnel syndrome. This procedure minimizes the disadvantage of medial instability and recurrent symptoms attributable to nerve trauma after a classic medial epicondylectomy. PMID- 11764353 TI - Magnetic resonance imaging of reconstructed anterior cruciate ligament. AB - After anterior cruciate ligament reconstruction with autologous patellar tendon, 23 patients who had clinically stable knees were studied prospectively with sequential magnetic resonance imaging 1, 2, 3, 6, and 12 months after surgery. The images of the anterior cruciate ligament were obtained with a 1.5 tesla magnetic resonance scanner in the oblique sagittal, coronal, and oblique axial planes. The cross-sectional area and signal intensity on the reconstructed anterior cruciate ligament were measured in an oblique axial image. The usefulness of the oblique axial image in evaluating the integrity of the reconstructed anterior cruciate ligament was seen. The result showed that the diameter of the graft increased by 70% of its initial size and the signal intensity of the reconstructed graft also showed a tendency to increase. In three patients, there was discontinuity in the graft direction on the oblique sagittal image, but on the oblique axial image there was no evidence of reconstructed anterior cruciate ligament rupture in the sequential images. This shows the value of the oblique axial image in evaluating the integrity of the reconstructed anterior cruciate ligament. Also, sufficient notchplasty in anterior cruciate ligament reconstruction may be needed to prevent graft impingement. PMID- 11764354 TI - Total knee replacement in patients with genu recurvatum. AB - Between June 1987 and March 1997, 57 total knee replacements were done in 53 patients with at least 5 degrees hyperextension deformity as measured on physical examination. The average recurvatum measured 11 degrees (range, 5 degrees-20 degrees). No cases of major ligamentous instability, neuromuscular disease, or inflammatory arthropathy were identified before surgery. Before surgery, Knee Society knee, function, and pain scores averaged 41 points, 41 points, and 13 points, respectively. A posterior cruciate-retaining prosthesis was implanted in all patients. The followup averaged 4.5 years (range, 3-10 years). Knee, function, and pain scores improved to 81 points, 78 points, and 43 points, respectively. Postoperative extension averaged 0 degrees (neutral) (range, 10 degrees hyperextension-10 degrees contracture). Only two (3.5%) knees had a hyperextension deformity after surgery. Both deformities measured 10 degrees and were in patients with a preoperative diagnosis of osteoarthritis. At final followup, no knee replacement was revised for any reason. In addition, only one case of a progressive radiolucent line greater than 1 mm (tibial Zone 7) was observed. Although the etiology of a hyperextension deformity should be elucidated before surgery, its presence does not preclude a well-functioning total knee replacement. PMID- 11764355 TI - The Otto E. Aufranc Award: The role of labral lesions to development of early degenerative hip disease. AB - The current authors examined the hypothesis that labral lesions contribute to early degenerative hip disease. Between 1993 and 1999, 436 consecutive hip arthroscopies were done by the senior author. In addition, 54 acetabula were harvested from human adult cadavers. Two hundred forty-one of the 436 (55.3%) patients who had arthroscopies had a 261 labral tears, all located at the articular, not capsular margin of the labrum. Stereomicroscopic examination of the 54 acetabula from cadavers revealed 52 labral lesions. Overall, there was no significant difference between the arthroscopic and cadaveric populations in terms of the incidence of labral tears. (Overall, 73% of patients with fraying or a tear of the labrum had chondral change. Arthroscopic and anatomic observations support the concept that labral disruption and degenerative joint disease are frequently part of a continuum of joint disease. PMID- 11764356 TI - Treatment of severe equinus deformity associated with extensive scarring of the leg. AB - Nine severe equinus deformities of the foot associated with extensive scarring of the leg and ankle were corrected using a hinged Ilizarov apparatus and free tissue transfer. The average duration of followup was 38 months (range, 28-54 months). Free tissue transfer was done in all patients; a parascapular flap was used in seven patients, and a groin flap was used in two patients. The results were evaluated using two objective criteria and one subjective assessment: the degree of active dorsiflexion, the range of active movement of the ankle, and daily activities. For active dorsiflexion of the ankle and activities, the results were good in seven patients and fair in two patients. For range of active motion of the ankle, the results were good in six patients and fair in two patients. One patient with ankle arthrodesis was excluded. This study showed that severe equinus deformities associated with extensive scarring of the leg and ankle can be corrected effectively with heel cord lengthening, free-tissue transfer, and a hinged Ilizarov technique. PMID- 11764357 TI - Cyclooxygenase-2 inhibitor for pain management in osteoid osteoma. AB - Thirteen patients with osteoid osteoma were enrolled in a prospective trial to test whether rofecoxib, a selective cyclooxygenase-2 inhibitor, is as effective for pain control as acetylsalicylic acid. Each patient documented the pain level using a visual analog scale, with 0 being no pain and 10 being unbearable pain, during 2 days of no pain medication, 4 days of 500 mg acetylsalicylic acid three times a day, and 10 days of 25 mg rofecoxib once a day. Oral administration of 500 mg acetylsalicylic acid three times a day led to a significant decrease in pain at night, pain at rest, and pain induced by exercise. Twenty-five milligrams rofecoxib given once a day at midday showed the same remarkable improvement in pain at night, pain at rest, and pain induced by exercise. Rofecoxib in comparison with acetylsalicylic acid showed a trend toward lower pain levels in all categories. Rofecoxib offered a significantly better reduction in pain at rest during the day than did acetylsalicylic acid. Results of the current study suggest that pain induction in osteoid osteoma is related to cyclooxygenase-2, an enzyme that is blocked by acetylsalicylic acid and rofecoxib. Conservative medical treatment with rofecoxib for osteoid osteoma is recommended when percutaneous intervention is associated with significant morbidity. PMID- 11764358 TI - Soft tissue reconstruction of megaprostheses using a trevira tube. AB - In soft tissue reconstruction of megaprostheses, the reattachment of soft tissue and joint capsules is essential. Sixty-nine megaprostheses were implanted and a trevira tube was applied to support reconstruction of the capsule and soft tissue. In cases of proximal femur replacement (33 patients), total femur replacement (five patients), and proximal humerus replacement (16 patients), the trevira tube allowed for reconstruction of the capsule and refixation of the muscles and helped to minimize dislocation. In cases of proximal tibia replacement (seven patients), arthrodesis of the knee (three patients), total knee replacement (two patients), and distal femur replacement (three patients), the trevira tube allowed for attachment of muscle flaps and extensor apparatus. Dislocation was observed in two of 54 patients who had proximal femur replacements. No dislocation was observed in patients with a total femur endoprosthesis or a proximal humerus endoprosthesis. The trevira tube also was used to attach the gastrocnemius muscle in patients with a proximal tibia endoprosthesis and to reattach the rotator cuff in patients with a proximal humerus prosthesis. There was no significant increase in the rate of infection. The histopathologic findings in six patients showed tissue ingrowth into the tube. PMID- 11764359 TI - Mechanical failure of unsupported Huckstep intramedullary nail in malignant bone tumor reconstruction. AB - Seventeen segmental resections of diaphyseal tumors and five knee resection arthrodeses were reconstructed using the Huckstep nail with intercalary bone grafts (fibula), cementation, and ceramic and titanium spacers. Although the bone defects were 0 to 25.5 cm in length (mean, 13.1 cm), all patients had relief of pain and were able to move alone with a wheelchair or a cane. Nail breakage occurred in four patients who had reconstruction surgery using a ceramic spacer (four patients without intercalary fibula graft and one patient with intercalary fibula graft). The nail survival rate was significantly better in the patients with reinforcement by vascularized fibular graft (100% at 5 years and 75% at 10 years; n = 8) than in the patients without reinforcement by vascularized fibular graft (87.5% at 3 years and 0% at 5 years; n = 14). Huckstep nailing is a useful option for reconstruction of large bone defects in diaphyseal tumors and knee resection arthrodesis. It should be used in combination with a vascularized fibula graft to prevent mechanical failure and to achieve durability of limbs with defects from primary bone tumors. Huckstep nailing with nonbiologic augmentation is good for palliative surgery for bone metastases in patients with a shorter expected survival rate. PMID- 11764360 TI - Pathologic fractures of the proximal femur secondary to benign bone tumors. AB - Pathologic fractures of the proximal femur secondary to benign bone tumors often are difficult to treat because of specific anatomic features of this region and the aggressiveness of the tumors. Between 1986 and 1996, 11 patients presented with a pathologic fracture of the proximal femur secondary to a benign bone tumor. All were treated with a uniform approach consisting of biopsy, intralesional curettage, high-speed burring, and reconstruction using morselized allograft, autograft, and a fixed-angle implant. The average followup was 4 years 3 months (range, 24-114 months). One patient was lost to followup. All fractures healed, and there were no local recurrences and no cases of avascular necrosis. Functional evaluation revealed generally good results. Patients scored a mean of 32.6 on the original Musculoskeletal Tumor Society scale and 95.8 on the revised version. The average Toronto Extremity Salvage Score was 91.3. With the numbers available, there were no significant differences between the study group and population norms in the Short Form-36. These results suggest that a uniform approach based on preservation of the femoral head can be applied successfully to the treatment of these lesions with good local tumor control, fracture healing, and acceptable functional outcomes. PMID- 11764361 TI - C-reactive protein in patients who had operative fracture treatment. AB - C-reactive protein as an indicator of infection, may help to detect surgical complications early and provide a better outcome for patients. To obtain a baseline for the use of C-reactive protein, the kinetics of C-reactive protein levels of 330 patients who had operative fracture treatment were studied before and after surgery. All patients who had an uneventful postoperative course had similar evolution in their C-reactive protein values: the peak level, which occurred on the second postoperative day, depended on the region of trauma (femoral fractures, 15.4 mg/dL versus ankle fractures, 3.5 mg/dL) and reflected the extent of surgical trauma. Of 47 patients with complicated courses, C reactive protein proved helpful as a marker in risk stratification and as an early indicator for infection. Of nine patients with a deep wound infection, a high rise of C-reactive protein was recorded, and seven patients showed a rise in the C-reactive protein level before the onset of clinical symptoms. A cut-off level of 14 mg/dL on the fourth day after surgery was recorded for the patients with deep wound infection. PMID- 11764362 TI - Dynamic magnetic resonance imaging of femoral head perfusion in femoral neck fracture. AB - A prospective followup study of 36 femoral neck fractures according to the assessment of femoral head perfusion using dynamic magnetic resonance imaging is reported. Patients were divided into three groups based on the dynamic magnetic resonance imaging findings (dynamic curve pattern and relative enhancement ratio) that were conducted within 48 hours of the injury. Traction was used to achieve anatomic reduction and to prevent additional damage to vascularity until minimally invasive internal fixation could be done. The fractures of all 17 patients whose femoral head perfusion was normal (Type A; n = 11) or was impaired but not totally absent (Type B; n = 6) healed without complications. Among the 19 patients whose femoral head perfusion was absent (Type C), 15 had complications (osteonecrosis, n = 10; nonunion, n = 5). Assuming that fractures with a Type A or Type B curve pattern would unite successfully and that those with a Type C curve pattern would not, the sensitivity, specificity, and accuracy of the predictions of successful osteosynthesis of the femoral neck fractures using this method were 81%, 100%, and 89%, respectively. The current classification of femoral neck fractures using dynamic magnetic resonance imaging may be useful in selecting an appropriate treatment method for the fractures. PMID- 11764363 TI - Chondrocyte death precedes structural damage in blunt impact trauma. AB - Joint impact trauma has been shown to cause fissures, fibrillation, and other structural damage of the cartilage or subchondral bone. Previous studies used impact energies sufficient to fracture the underlying bone. Under these circumstances, the initial influence of impact trauma on cellular components and cartilage structure is unknown. The goal of this study was to determine whether an impact trauma first causes cellular or structural damage to a cartilage layer. Such damage might be the starting point of degenerative changes found in osteoarthrosis. Porcine patellas (n = 12) were subjected to standardized low impact loading of three magnitudes with a spherical impactor attached to a drop tower device (0.06, 0.1, and 0.2 J). India ink staining and scanning electron microscopic analysis were used for analysis and showed no evidence of gross structural disruption. Chondrocyte viability assessed with thiazole blue staining and propidium iodide counterstaining was reduced significantly in the tangential and middle zones with increasing impact energy. These results indicate that chondrocyte death may precede excessive structural damage reported in earlier studies and might be a crucial factor in posttraumatic osteoarthrosis. PMID- 11764364 TI - Accuracy of computer-guided screw fixation of the sacroiliac joint. AB - Computer-assisted image guidance allows precise preoperative planning and intraoperative localization of surgical instruments. The technique recently was validated for the insertion of pedicle screws. In the laboratory, the precision of a surface-matching algorithm was evaluated for registration and accuracy and safety of screw placement into the vertebral bodies of S1 and S2 for fixation of the sacroiliac joint. Using six plastic pelves, 24 screw holes were made through the sacroiliac joint into the vertebral body of S1, and 12 holes were made through the sacroiliac joint into S2. The accuracy of the hole position was evaluated using a postoperative computed tomography examination. The safety factor was assessed by analysis of the remaining bone stock around the holes calculating a theoretical cylindrical volume being outside bone with increasing bore hole diameters. The registration was accurate with a mean error less than 1.4 mm in the posterior parts of the pelvis. The drilling followed precisely the preoperatively planned trajectories; perforation of the cortex of the sacrum was not observed. The safety factor of the S1 vertebral body is higher than that of S2 allowing larger diameter screw insertion into S1. This technique provides a safe and precise guide for transcutaneous or open insertion of iliosacral screws in cases of iliosacral dislocation or sacral fracture. PMID- 11764365 TI - Biomechanical efficacy of an internal fixator for treatment of distal radius fractures. AB - Despite the effectiveness of external fixation in the treatment of complex wrist fractures, the complication rate for this modality ranges from 20% to 62%. Common complications are related to the use of percutaneous metal pins and result in an average reoperation rate of 16%. In addition, external fixation is unable to prevent dorsal collapse of the radius or maintain the normal palmar tilt of the radiocarpal joint surface. This complication may predispose to posttraumatic wrist instability and arthritis. The problems with external fixation have prompted a search for a better treatment option. An internal fixator placed through limited incisions on the dorsal aspect of the radius and spanning the fracture site can, in theory, provide the benefits of external fixation without the associated morbidity. This study determined the biomechanical efficacy of internal fixators compared with external fixators using a standardized model for an unstable wrist fracture. Two commercially available metal plates were used as internal fixators. Biomechanical testing of the devices was done, and stiffness was determined. Results showed that the internal fixators were significantly stiffer than were the external fixators in axial loading. Failure in axial loading, specifically compression, is a consistent reason for loss of reduction in intraarticular distal radius fractures. The clinical implications of these results suggest that an internal fixator theoretically can prevent loss of reduction in the axial plane and maintain palmar tilt by acting as a rigid dorsal buttress. In addition, the use of an internal fixator potentially decreases the high morbidity associated with external fixation. Additional investigation into the clinical application of internal fixators for distal radius fractures is needed. PMID- 11764366 TI - Contributions of active and passive toe flexion to forefoot loading. AB - Toe flexion during terminal stance has an active component contributed by the muscles that flex the toes and a passive component contributed by the plantar fascia. This study examined the relative importance of these two mechanisms in maintaining proper force sharing between the toes and forefoot. Thirteen nonpaired cadaver feet were tested in a dynamic gait stimulator, which reproduces the kinematics and kinetics of the foot, ankle, and tibia by applying physiologic muscle forces and proximal tibial kinematics. The distribution of plantar pressure beneath the foot was measured at the terminal stance phase of gait under normal extrinsic muscle activity with an intact plantar fascia, in the absence of extrinsic toe flexor activity (no flexor hallucis longus or flexor digitorum longus) with an intact plantar fascia, and after complete fasciotomy with normal extrinsic toe flexor activity. In the absence of the toe flexor muscles or after plantar fasciotomy the contact area decreased beneath the toes and contact force shifted from the toes to the metatarsal heads. In addition, pressure distribution beneath the metatarsal heads after fasciotomy shifted laterally and posteriorly, indicating that the plantar fascia enables more efficient force transmission through the high gear axis during locomotion. The plantar fascia enables the toes to provide plantar-directed force and bear high loads during push-off. PMID- 11764367 TI - Femoral stem insertion generates high bone cement pressurization. AB - Adequate bone cement pressurization is critical in obtaining optimal femoral cement mantles during total hip arthroplasty. Pressurization can be generated during insertion of the femoral stem into the cement-filled canal. This may be clinically useful in augmenting conventional cement gun pressurization. Two factors, which were expected to influence the amount of insertion-induced pressurization, are the cement's cure state (viscosity) at the time of insertion and the femoral stem profile. This study evaluated the effect of these factors on cement pressurization during stem insertion. Femoral stems were inserted at a controlled rate into a reusable, simulated femoral canal. Intramedullary pressures were monitored at four locations along the canal's medial midline. The intrusion factor quantity, which accounts for pressure magnitude, duration of pressurization, and cement viscosity, was developed to quantify pressurization. Stem insertion into late cure stage (high viscosity) cement resulted in significantly higher intramedullary pressures (as much as 187% higher) and intrusion factors (as much as 43% higher) as compared with early stage (low viscosity) cement. The highest pressures and intrusion factors were found in the distal canal. A tapered stem profile resulted in significantly higher pressures (as much as 65%) and higher intrusion factors (as much as 63%) than a straight stem. PMID- 11764368 TI - Knee pain in a 16-year-old girl. PMID- 11764369 TI - The John Charnley Award: Three-dimensional analysis of the cement mantle in total hip arthroplasty. AB - Cemented fixation of the femoral stem is the gold standard for patients older than 60 years. The importance of reliably achieving an adequate cement mantle has been shown in many studies. Currently, inspection and grading of plain radiographs is the accepted method for study of the cement mantle. However, the reliability of plain radiographs for this purpose has been questioned. In addition, the interobserver agreement of current grading systems has been shown to be limited. A new in vitro method of cement mantle analysis is described. Plastic replicas of six contemporary stems were implanted into femurs from cadavers. The specimens were imaged with a computed tomography scanner. Detailed, computer-assisted analysis of mantle thickness was done. Comparisons were made between designs. A subset was compared with standard radiographs. Plain radiographs overestimated thickness and underestimated the deficiencies. There was significant variability in the mantle produced by the different designs. Commonly used designs had deficiencies in their mantles by standard criteria despite proper surgical technique. The importance of being fully acquainted with the particular implant one uses is emphasized by these results. This is a valuable technique for investigation of the effects on the cement mantle of implant design, surgical technique, and patient anatomy. PMID- 11764370 TI - Alcoholism, hypercortisonism, fat embolism and osseous avascular necrosis. 1971. PMID- 11764371 TI - The Frank Stinchfield Award: Morphologic features of the acetabulum and femur: anteversion angle and implant positioning. AB - Morphologic features of the hips, in particular those features germane to determination of acetabular and femoral anteversion angles and femoral head offset, were studied in 50 male and 50 female human skeletons with bilateral normal joints. Four distinct configurations were identified relative to the anterior acetabular ridge. The majority (121, 60.5%) were curved; 51 (25.5%) were angular; 19 (9.5%) were irregular; and nine (4.5%) were straight. The acetabular anteversion angle measured 19.9 degrees +/- 6.6 degrees (range, 7 degrees-42 degrees) and was significantly larger in females (21.3 degrees +/- 7.1 degrees) versus males (18.5 degrees +/- 5.8 degrees). The notch acetabular angle, which can be identified easily intraoperatively, was defined as the angle created at the intersection of a line from the sciatic notch along the posterior acetabular ridge and a line from the posterior to the anterior acetabular wall. This angle is almost perpendicular (89.0 degrees +/- 3.5 degrees) and, therefore, may provide an accurate estimate of acetabular anteversion during cup placement. Awareness of the anatomic differences between genders for acetabular anteversion angle, anterolateral bowing of the femur, and neck shaft angle may help reduce the relatively higher incidence of dislocation in females and may lead to different implant designs for male and female patients. PMID- 11764372 TI - Wear and periprosthetic osteolysis: the problem. AB - The dominant long-term problem in total hip replacement surgery, and an important problem in total knee replacement surgery, is wear of the polyethylene and its resulting periprosthetic osteolysis. Several of the key features of this unique disease are presented focusing on the importance of periprosthetic osteolysis, comprehension of the general progressive nature of periprosthetic osteolysis, understanding of the diverse radiographic evidence of this disease, and the consequences that can occur from the disease. PMID- 11764373 TI - Osteolysis: basic science. AB - Since the recognition of aseptic loosening by Charnley in the early 1960s, much information has been gained on the basic science of periprosthetic bone loss. Initially termed cement disease, it now generally is accepted that, in most instances, osteolysis is a manifestation of an adverse cellular response to phagocytosable particulate wear and corrosion debris, possibly facilitated by local hydrodynamic effects. Tissue explant, animal, and cell culture studies have allowed us to compile an appreciation of the complexity of cellular interactions and chemical mediators involved in osteolysis. Cellular participants have been shown to include the macrophage, osteoblast, fibroblast, and osteoclast. The plethora of chemical mediators that are responsible for the cellular responses and effects on bone include prostaglandin E2, tumor necrosis factor-alpha, interleukin-1, and interleukin 6. However, an increasing number of other proinflammatory and antiinflammatory cytokines, prostenoids, and enzymes have been shown to play important roles in this process. The ultimate goal of basic research is to develop novel strategies for evaluation and treatment of patients with osteolysis. Although initial animal studies are promising for possible pharmacologic treatment and prevention of osteolysis, well-controlled human trials are required before agents such as bisphosphonates can be recommended for general clinical use. PMID- 11764374 TI - Surgical treatment of pelvic osteolysis. AB - Sixty-eight well-fixed acetabular cups with osteolysis in the pelvis and polyethylene wear were identified from a series of 124 reoperations for failed cementless sockets. The well-fixed sockets requiring reoperation were subdivided based on whether the liner was exchanged and lytic lesion grafted (Type I case) or the socket was removed and a complete revision was done (Type II case). In 40 patients (Type I cases), the polyethylene liner was exchanged and the osteolytic lesions were debrided. Allograft bone chips were packed into the lytic defect in 29 patients. In the remaining 11 patients, the lesions were debrided but not grafted. At final followup, all of the acetabular components were radiographically stable. No new osteolytic lesions were identified. Approximately 1/3 of the lesions had resolved completely regardless of whether they were grafted. The remaining 2/3 had decreased in size. In 28 patients (Type II cases), the socket was revised. Both strategies were successful in arresting the process of osteolysis during the course of this study (mean, 3.5 years). However, removal of well-fixed sockets was associated with significantly more bone loss. PMID- 11764375 TI - Prevention of wear and osteolysis: alumina-on-alumina bearing. AB - Alumina-on-alumina bearings in total hip replacement have been used for 30 years. Excellent tribologic properties and extra low debris generation could, in theory, provide an answer to osteolysis. A review of the authors' experience with alumina on-alumina bearings showed that, except in a few bearings that had been loose for a long time, osteolysis was not a problem. Although the cemented titanium stem and the alumina-on-alumina couple were not a problem, fixation of the socket had to be improved. To improve the socket fixation system and to avoid the use of a cemented titanium stem that may have created problems in the long-term, a new design was introduced in 1997. The current authors present the preliminary results of the first 96 hips with cementless fully-coated hydroxyapatite titanium alloy stems and sockets, 32-mm alumina femoral head, and alumina liner, both held with a Morse taper. Ninety-six consecutive hips in 89 patients (57 males, 32 females) with a median age of 46 years (range, 14-72 years) were analyzed. One socket was revised at 4 months because of poor primary stability in a patient with a severe acetabular fracture. One patient experienced a traumatic fracture of the implanted femur 3 weeks after surgery. The mean followup was 16 months (range, 4-38 months). One patient died from rupture of an aneurysm. Ninety-three hips in 86 patients were assessed regarding the clinical and radiologic ratings. Two patients (two hips) were interviewed by telephone. The Merle d'Aubigne rating system was 18 in 65 hips (59 patients), 17 in 25 hips (25 patients), and 16 in three hips (three patients) mainly related to a previous disability including limp, sciatic palsy, or stiffness. Examination of 93 available radiographs revealed no ostelolysis, no radiolucent lines at the last examination, and no subsidence. The level of excellent results, even in this young population, and lack of osteolysis and wear are encouraging, even if the followup is too short to allow any conclusions to be made. PMID- 11764376 TI - Direct compression molded polyethylene for total hip and knee replacements. AB - Direct compression molded polyethylene is a process of creating a net-shaped component with finished articular surfaces from ultrahigh molecular weight polyethylene by applying heat and pressure to the raw resin (usually Hi-fax 1900) with the use of fixed geometry metallic tools. The final product has no machining or finishing. Sterilization was by gamma radiation in air. Between 1974 and 1978, there were 378 cemented T-28 stems (321 patients) and 171 cemented TR-28 stems (158 patients) articulating with a cemented direct compression molded acetabular component. Radiographically, linear wear was 0.06 mm per year for the T-28 stem and 0.05 mm for the TR-28 stems. The revision rates for the acetabulum were 9.5% and 7.9%, respectively with only two acetabula having osteolysis. On the femoral side, the revision rates were 11.1% and 12.8%, with 11 cases and one case of osteolysis, respectively. Between 1983 and 1996, 4583 AGC cemented total knee replacements were done with direct compression molded nonmodular tibial components. There was no osteolysis seen in these nonmodular compression molded total knee replacements even with 0.1% failure of the femoral components and 0.4% failure of the tibial components. Failure of all of the hip and knee implants was because of poor cement technique, instability, or both. Wear and osteolysis were minimal. Direct compression molded polyethylene has stood the test of time and is a good choice among the currently available polyethylenes. PMID- 11764377 TI - ADASP recommendations for processing and reporting of lymph node specimens submitted for evaluation of metastatic disease. AB - It is well known that different pathologists in different laboratories follow different protocols for the processing and examination of these specimens. There is also extensive literature (some of which is summarized in the references appended to the present report) on the likelihood of identifying metastases of varying sizes with different methods of preparation, as well as on the clinical significance of this identification, which varies not only from site to site but also from report to report on the same site. The Association of Directors of Anatomic and Surgical Pathology (ADASP) has reviewed this literature as well as the personal experience of its own members to present a set of recommendations for lymph node biopsies, lymph node dissections, sentinel node biopsies, lymph node fine needle aspiration (FNA) and core needle biopsies. It should be noted that these recommendations are intended specifically for lymph nodes being studied for metastatic neoplasms, and are not intended to apply to lymph nodes being evaluated for lymphoma, infections, and other disease processes. They are, however, formulated generically enough to apply regardless of whether the primary tumor is a carcinoma of the breast, carcinoma of the prostate, melanoma, or any other malignant, potentially metastasizing tumor. The Association has published numerous documents with recommendations for reporting surgical pathology specimens involving particular organ sites (for example, breast, pancreas, thyroid, etc.) However, the Association has not yet considered the generic question of dealing with lymph node specimens in which the intent is to search for and document the presence of metastatic disease. We are also unaware of guidelines for pathologists published by any other organization on this subject. PMID- 11764378 TI - The histological diagnosis of endometrial hyperplasia. Is there a need to simplify? AB - The intra- and interobserver variability of the histological diagnosis of endometrial hyperplasia, including low-grade carcinomas, is high and thus often causes confusion in the dialogue between pathologists and clinicians. The current classification of the WHO, ISGP, and FIGO is not altogether successful in overcoming this difficulty. New approaches to resolve this unsatisfactory situation have been suggested by two recent simultaneous studies, one by a European group of experts (1999) and the other by Mutter and The Endometrial Collaborative Group (2000). Both studies suggest simplifying the WHO classification by reducing the present four categories to two. The European study names the new histological groups endometrial hyperplasia (EH) and endometrioid neoplasia (EN), while Mutter et al. call them endometrial hyperplasia (EH) and endometrial intraepithelial neoplasia (EIN). Differentiation between the two new categories can be made based on uncomplicated morphological concepts and confirmed morphometrically by the semiquantitative determination of the stromal volume in relation to total tissue volume (stroma+epithelium+gland lumen). This simplification has the advantage of a high degree of reproducibility of histological diagnoses while facilitating understanding by clinicians. Most importantly, there is no decrease in prognostic accuracy, since EH is a benign lesion, easily treated with hormones and almost without risk of progressing to cancer, while EIN/EN is a pre- or already malignant disease with a high risk of progression (approximately 30%) requiring a more radical treatment. This article summarizes the current discussion on this issue. PMID- 11764379 TI - Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomas. AB - The histogenesis of primary nonurachal mucus-producing adenocarcinomas of the urinary bladder including signet ring cell carcinomas remains to be elucidated, since the normal bladder contains neither columnar nor mucus-secreting glandular epithelium. Based upon the assumption that adenocarcinomas may develop secondarily from pre-existent transitional cell carcinomas (TCC) by a metaplastic process, it was the purpose of the current immunohistochemical study to analyze whether urothelial carcinomas are capable of secreting MUC5AC apomucin, using the monoclonal antibody 45MI. This antibody has been initially demonstrated to strongly react with the mucus-producing columnar cells of the surface gastric epithelium, recognizing a specific epitope located on the peptide core of glycoproteins as major components of mucins. Nine of 64 uniformly differentiated papillary (14.1%) and 5 of 66 nonpapillary (solid) TCC with a uniform urothelial differentiation (7.6%) expressed the MUC5AC antigen, yielding an overall incidence of 10.8%. Transitional cell carcinomas with a focally altered cellular and structural differentiation (squamous cell, pseudoglandular, true glandular and mixed differentiation) stained positively in a substantially higher percentage of 43.8% (21 of 48 cases). A positive immunoreactivity was also observed in 3 of 19 mixed transitional cell and nonurothelial carcinomas. The tumor-associated resurgence of normally cryptic MUC5AC antigenic determinants in transitional cell carcinomas is considered as a re-expression of oncofetal antigenicity, probably as a result of the embryologic origin of the urinary bladder from the pluripotent tissues of the cloacal endoderm and the mesodermal wolffian ducts. Our findings may help to better understand the histogenetic development of mucus-secreting vesical adenocarcinomas from pre-existent urothelial carcinomas. PMID- 11764380 TI - Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors. AB - Nonseminomatous components within testicular germ cell tumors affect patient prognosis to varying degrees. These components are well known to mimic early embryonic totipotential tissues. Prompted by the recent observation that fibroblast growth factor (FGF) 8, FGF4, and FGF receptor (FGFR) 1 are required for the growth of early postimplantational embryonic tissues, we investigated the expressions of FGF8, FGF4, and FGFRI in surgically resected specimens of primary testicular germ cell tumors using an immunohistochemical method. All cases of embryonal carcinoma (14 cases), yolk sac tumor (3 cases), and choriocarcinoma (3 cases) showed positive immunostaining for FGF8, FGF4, and FGFR1. In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively. In 7 cases of mature and immature teratoma, most areas showed negative immunostaining. In addition, the Ki-67 labeling index showed extremely high mitogenic activity in embryonal carcinoma, yolk sac tumor, and choriocarcinoma, which are precisely the carcinomas with the highest expressions of FGF8, FGF4, and FGFR1. It is in keeping with the immunohistochemical result that murine teratocarcinoma P19 cells were shown to express FGF8, FGF4, and FGFRI only under undifferentiated growth conditions. Taken together, these findings confirm the involvement of FGF8, FGF4, and FGFR1 in highly proliferative conditions of nonseminomatous germ cell tumors. PMID- 11764381 TI - Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinoma. AB - Loss of human mismatch repair (hMSH2) gene function has been linked to hereditary non-polyposis colorectal cancer (HNPCC), Muir-Torre syndrome (MTS), and sporadic cancers, excluding skin cancers unrelated to MTS. We immunohistochemically examined 125 squamous cell carcinomas (SCCs) using a monoclonal antibody to the hMSH2 protein and compared the results with those for 106 precursor lesions of SCC, consisting of actinic keratosis (AK), Bowenoid type of actinic keratosis (BAK), and Bowen's disease (BOD). In contrast to the homogeneous immunoreactivity of proliferating cells composed of AK, BAK, and BOD, heterogeneous and diminished immunostaining to hMSH2 was observed in tumor cells of SCCs examined. In addition, two SCCs (2 of 125; 1.6%) at multiple loci exhibited a complete lack of immunoreaction to hMSH2. Immunohistochemical staining of hMSH2 was semiquantitatively scored as 0 (0% of total cells examined), 1 (less than 10%), 2 (10-50%), or 3 (more than 50%). Percentage preservation of and average score for hMSH2 expression in normal, AK, BAK, BOD, and SCC were 56% and 2.06, 100% and 2.80, 94% and 2.88, 83% and 2.78, 63% and 2.36, respectively. The percentage preservation of and average scores for hMSH2 in AK, BAK, and BOD were significantly higher than those in presumably normal skin (P<0.01). There were no significant differences in the percentage preservation of and average scores for hMSH2 between presumably normal skin and SCC. The score for hMSH2 expression was significantly correlated with score for sun exposure in presumably normal skin of each lesion (R=0.70). These findings for hMSH2 expression in precursor lesions and SCC suggest that promotion or activation of hMSH2 expression may be induced by the increased DNA damage caused by sun exposure and that diminished expression of it might occur according to the transformation from precancerous lesions to SCC. PMID- 11764382 TI - Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma. AB - We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.0 mm, and one-third of these tumors proved to be positive irrespective of the thickness. Patients were followed for a minimum of 61 months. The onset of lymph node or organ metastases occurred not later than 58 months and 60 months, respectively. Of the 15 CD44v3 positive tumors, 14 were observed in the organ metastatic tumor group, comprising the majority of those cases (14 of 21), and this association proved to be statistically significant compared with the non metastatic (P<0.05) and lymph-node metastatic cases (P<0.01). CD44v3 expression in melanoma was also confirmed at the protein and messenger (mRNA) level in several human melanoma cell lines using flow cytometry and reverse transcriptase polymerase chain reaction analysis. In parallel to CD44v3, MMP-2 expression (determined using immunohistochemistry) was significantly elevated (P<0.05) but only in the organ metastatic group of MM. The 5-year survival of patients having thicker tumors than 1.0 mm (where v3 expression occurred) who had CD44v3+ tumors was significantly lower than those of the negative ones (35.7% versus 68.2%, respectively; P=0.025). Finally, we observed that the CD44v3-expressing tumors were characterized by significantly higher MMP-2 expression than the CD44v3 negative tumors (P<0.001), indicating a possible correlation between CD44v3- and MMP-2-positive phenotype and the organ metastatic potential of MM. PMID- 11764383 TI - Aneurysmal bone cyst of the nose with 17p13 involvement. AB - We report on a 6-year-old girl with a polypoid mass, filling up the entire right nasal cavity as shown on a magnetic resonance imaging scan. Histologically, the tumor had the characteristics of an aneurysmal bone cyst, which is extremely rare in this location. Cytogenetic analysis disclosed a single (6:17)(p21;p13) translocation, confirming a specific genetic involvement in the development of aneurysmal bone cysts. Fluorescent in situ hybridization analysis mapped the putative gene between the p53 (17p13.1) and the Mieller-Dieker gene (17p13.3) loci. PMID- 11764384 TI - Aortic lesions in aspergillosis: histopathological study of two autopsy cases. AB - The involvement of the aorta in aspergillosis is relatively rare, and its histopathological features have not been described in detail. In two autopsy cases of invasive aspergillosis in immunologically compromised patients with hematological disorders, the aspergillotic lesions of the aorta showed different characteristic histopathological features depending on the three layers of aortic wall. Intimal lesions were formations of the mural thrombus composed of aggregates of numerous fungal hyphae arranged perpendicularly to the aortic wall. In the media, smooth muscle cells were completely necrotic (anemic infarct of the media), while the framework of elastic fibers was well preserved, with only a few fungal hyphae detected. In the adventitia, an intense, partly granulomatous chronic inflammatory change with fibrosis was observed in association with mycotic embolic occlusion of the vasa vasorum. These histopathological changes were considered to represent one of the typical tissue reaction patterns in the wall of an elastic artery in aspergillosis. PMID- 11764385 TI - Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas. AB - Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF(121,165) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy. PMID- 11764386 TI - Helicobacter pylori, N-methyl-N'-nitro-N'-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer. AB - Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori. PMID- 11764387 TI - Effects of Helicobacter pylori and bile on N-methyl-N'-nitro-N'-nitrosoguanidine exposed antral mucosa of C57BU6 mice. AB - The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N' nitro-N'-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions. PMID- 11764388 TI - Osteopontin expression in primary sarcomas of the pulmonary artery. AB - Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction. The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes. Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas. PMID- 11764389 TI - Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis. AB - Collagen type IV is a structural matrix protein which contributes to the structural organization of the synovia. In order to characterize the distribution of this protein in synovia with chronic synovitis, collagen type IV was detected by immunochemistry in normal synovia and in synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). A decrease of collagen type IV was observed in synovial layers of rheumatoid synovia, which statistically correlated with the grade of inflammation and with the thickness of the synovial layer. In vitro, we found no differences in the gene expression of collagen type IV in cultures of fibroblast-like synoviocytes (FLS) derived from OA and RA using a reverse-transcriptase polymerase chain reaction. Nevertheless, we observed a downregulating effect of tumor necrosis factor-alpha and interleukin (IL)-1beta on the gene expression of collagen type IV only in FLS isolated from patients with RA. The effect of IL-1beta was dose dependent. In summary, we observed an inflammation-associated decrease of collagen type IV in the synovial layer of rheumatoid synovia. Inflammatory cytokines may play a role in regulating the synthesis of collagen type IV in the rheumatoid process in vivo. PMID- 11764390 TI - Cytological characterization of apatitic calcium phosphate structures in bronchial epithelial tissue cultured from a child with cystic fibrosis (deltaF508). AB - Patients with cystic fibrosis homozygous for the AF508 mutation have marked disturbances in ion exchanges in a variety of tissues. Alterations in intra- or extracellular levels of Ca2+ and calcifications have been observed in numerous tissues from such patients, although the nature and origin of such calcifications have yet to be elucidated. In this study, we investigated the formation of calcifications in the respiratory tract of a AF508 homozygous child and attempted to establish their origin. Samples of bronchial epithelium from this patient were subjected to cytophysiological analysis ex vivo and in vitro. The defect of targeting of the cystic fibrosis transmembrane conductance regulator (CFTR) to the apical plasma membrane of epithelial cells was verified. Cytochemical and ultrastructural analysis revealed the presence of crystalline aggregates in fine needles in the respiratory tract. Cytochemical analysis, X-ray spectrometry, and electron diffraction showed that these aggregates corresponded to crystals of calcium phosphate in an apatite-like structure. Ultrastructural study of primary cultures of bronchial epithelium showed the presence of calcium phosphate crystals in granules from Golgi apparatus and in mitochondria. These observations indicated that modifications of ionic exchanges due to a defect in targeting of CFTR AF508 to the apical plasma membrane led to the formation of crystals of calcium phosphate in the cytoplasm of pulmonary cells. These crystals could enhance inflammation of the lung in patients with cystic fibrosis. PMID- 11764391 TI - Hodgkin's disease with an intrasinusoidal pattern of infiltration. A report of two cases. AB - The histological distinction between Hodgkin's disease (HD) and anaplastic large cell lymphoma (ALCL) may be difficult but is important as the two conditions have different clinical behaviours, prognoses and responses to therapy. Morphological appearances that have been emphasised as favouring the diagnosis of ALCL rather than HD include the identification of neoplastic cells permeating sinusoidal spaces. We document two cases of Hodgkin's disease with classical morphological and immunohistochemical features of nodular-sclerosis subtype (HDNS) but with striking sinusoidal involvement by neoplastic cells. In each case, the CD30 positive/CD15 positive immunophenotype of the neoplastic cells was characteristic of HD without expression of any of the other antigens normally associated with ALCL. HD is generally considered to be a morphological diagnosis and, in those laboratories in which it is not possible to use wide panels of antibodies for the confirmation of the diagnosis, the identification of sinusoidal infiltration by the neoplastic cells in HD may lead to the mistaken impression of ALCL. PMID- 11764392 TI - Ancient schwannoma of the pancreas mimicking a cystic tumor. PMID- 11764393 TI - Malignant mixed epithelial and stromal tumor of the kidney. PMID- 11764394 TI - Recommendations for a mammography quality assurance program. AB - In 1989 the ACPSEM published a position paper entitled "A Quality Assurance Programme for Mass Screening in Mammography". This paper described test parameters and performance specifications for the equipment related aspects of a mammography quality assurance program. Advice on test equipment selection was also provided. In the intervening period of time there have been considerable advances in mammography technology creating a need to review a number of the paper's recommendations. There have also been considerable developments in the mammography quality assurance (QA) field, not the least of which includes the American College of Radiology Mammography Accreditation Program (ACR-MAP) and the similarly structured Royal Australian and New Zealand College of Radiologists' Mammography Accreditation Program (RANZCR-MAP). In light of these developments it was decided by the Radiology Interest Group to review the ACPSEM position on those aspects of mammography QA that fall within the medical physicist's area of expertise. This document represents the outcome of those deliberations. PMID- 11764395 TI - The use of the linear quadratic model in radiotherapy: a review. AB - To be able to predict the impact of any radiotherapy treatment the physics of radiation interactions and the expected biological effect for any radiotherapy treatment situation (dose, fractionation, modality) must be both understood and modelled. This review considers the current use and accuracy of the linear quadratic model which can be used to consider the variation in tissue response with fraction size. Cell kill following radiation damage results from damage to the DNA which can take a variety of forms. In many cases the linear quadratic model is used to estimate the relative impact for different situations especially clinical studies relating to fraction size. This is mainly undertaken using parameters derived from the linear quadratic model such as biological effective dose and standard effective dose. The model has also been adapted to consider the effect of overall treatment time, repair during treatment (as occurs for brachytherapy treatments) and other situations. There are some concerns over its use, mainly in the small dose ranges (both total low doses and low doses per fraction) where studies have shown its inaccuracy. In other situations however it does appear to provide a reasonable estimate of relative clinical effect. As with all models, however results should never be considered out of clinical context. PMID- 11764396 TI - The effect of source-axis distance on integral dose: implications for IMRT. AB - The source-axis distance (SAD) is a treatment machine design parameter that affects integral dose, dose rate and patient clearance. The aim of this work was to investigate the effect of source-axis distance on integral dose for conformal arc therapy. This work is part of a larger project to determine the ideal characteristics of a dedicated IMRT machine. The sensitivity of SAD to beam energy, PTV size, body size and PTV position were determined for conformal arc therapy. For the calculations performed here it was assumed that dose equals terma. The integral dose ratio (IDR) was used to quantify the calculation results. It was found that the IDR increases as both SAD and photon energy increase, though the dependence of IDR on SAD decreases as energy increases. The PTV size was found to have a negligible effect on the relationship between the SAD and IDR, however the body size does affect the relationship between the SAD and IDR. The position of the PTV within the body also affects the IDR. From dosimetric considerations alone, the larger the SAD, the better the possible dose distribution. The IDR for a very large SAD is increased by approximately 5% when compared with the IDR for 100 cm SAD. Similarly, the IDR for 100 cm SAD is approximately 5% higher than the IDR at 50 cm SAD. PMID- 11764397 TI - Proposal for a gamma-emitting stent for the prevention and treatment of coronary artery restenosis. AB - Radioactive stents have failed to prevent restenosis despite the demonstrated success of other radionuclide therapies using beta- or gamma-emitting radionuclides in the coronary arteries. This may be due to the rapid dose reduction at the end of the stent that occurs with a stent coated with 32P, which is a pure beta-emitter. A gamma-emitter will give a greater dose beyond the end of the stent and would therefore be expected to produce better results. However, it is essential that the gamma-emitter is not contaminated with beta particles of either sign nor with conversion electrons. This requirement generally demands the use of a high energy gamma-emitter, preferably with an energy greater than 500 keV. High energy gammas have other advantages, including a high radiation dose delivered per decay which reduces the total activity required and reduced dose near to the source due to electron disequilibrium. The ideal dose distribution is one that provides a uniform dose to the proliferating tissues and a reduced dose elsewhere. Although the target tissues are not well defined it is believed that the adventitia is the source of the proliferating cells. Hence the target tissue is between 0.5 and 2 mm depth into the artery. It is shown that 96Tc is a very suitable radionuclide for the production of radioactive stents giving a significantly greater dose compared with 32P both at depth and beyond the end of the stent for the same dose at the surface of the stent. Furthermore, 96Tc should be able to be made with a standard medical cyclotron and may be coated on to a stainless steel stent by a simple process that takes approximately 30 minutes to perform. Its half-life of 4.3 days will allow radioactive stents to be transported over significant distances and will result in a treatment time with a mean value of approximately 1 week. This will allow the rapid reestablishment of the endothelial layer which may be a further advantage of this radioactive stent. PMID- 11764398 TI - The use of 188Re to treat in-stent re-stenosis of coronary arteries. AB - A pilot study has been conducted in which coronary arteries subject to re stenosis after angioplasty and stenting have been irradiated following further angioplasty. The method of irradiation has been to use radioactive 188Re in an angioplasty balloon. This paper considers all aspects of the procedure including elution of the rhenium from a tungsten/rhenium generator, its concentration, dispensing and safe delivery to the patient using specially designed equipment to reduce staff doses and radioactive spills. In the pilot study of 28 lesions in 26 patients only 1 was recorded as having angiographic re-stenosis in the treated region at 6 months although 4 other patients had edge re-stenosis. This represents less than 18% re-stenosis in a population that would have been expected to exhibit at least 50% re-stenosis at 6 months. A total of 72 patients have been treated either in the pilot study or a subsequent trial. In only one case has a minor spill of radioactivity occurred and in no case has the balloon burst. Radiation doses to staff are approximately 20 microSv per procedure and are therefore not of serious consequence. It is concluded that this procedure is safe, feasible and effective in reducing in-stent re-stenosis. PMID- 11764399 TI - Determination of radiographic characteristics of tissue compensation filters using a compton scatter technique. AB - Tissue compensation filters (TCF) aid in plain film radiographic examinations by reducing the range of radiographic densities in the film. The composition and shape of the TCF assists in reducing radiographic density ranges that result from large anatomical density differences within the patient. The reduction of large density ranges on a radiographic film allows the clinicians to visualise larger ranges of anatomy. A Compton scatter technique has been used to examine the changes in the x-ray spectra that result from the placement of various TCF materials and thicknesses in the primary x-ray beam. Difficulties in the use of the Compton scatter technique in the examination of TCF under clinical conditions are discussed. Conclusions have been reached that will enable clinicians to optimising the x-ray tube voltage (kVp) so to maximise the effectiveness of each TCF material examined. The term spectral shift has been defined to aid in the evaluation of the TCF's effect on x-ray spectral changes. Maximum spectral shift for each type of TCF material occurs between generator settings of 70 - 80 kVp. TCF spectral shift changes were also examined under typical clinical generator types. Maximum spectral shift occurs when TCF are used with single phase, 100% ripple generators. Dose reduction conclusions from the use of the TCF are also discussed. PMID- 11764400 TI - The clinical value of ophthalmic electrodiagnosis in children. AB - A group of 113 children with poor vision who had been referred to the Electrodiagnostic Clinic over a five year period were investigated for disease of the retina and optic pathway by electroretinography (ERG), electro-oculography (EOG) and visual evoked response (VER). The electrodiagnostic measurements were made using an automated system developed at Christchurch Hospital. The results of these investigations confirmed the clinical value of ophthalmic electrodiagnosis both as an aid in the diagnosis of these young patients and in determining their prognosis. In some cases it permitted an early detection of their condition. In addition the analyses of the ERG into rod and cone mediated responses helped to establish the diagnosis of hereditary retinal disorders and was particularly useful in the case of infants with nystagmoid movements of the eyes who were suspected of having poor vision. Interestingly 21 of the 113 patients were found to have functional visual loss. These patients complained of visual loss but subsequent examinations revealed their ocular findings, EOG, ERG and VER were all normal. The age of this functional visual loss group ranged from 7 to 15 years, with the average being 11.3 years (SD = 2.6 years). Furthermore they were a large group representing 32% of all the children between 7 and 15 years and in most cases were not happy at school. PMID- 11764401 TI - Verification of ophthalmic brachytherapy treatment planning. AB - Ophthalmic brachytherapy dose calculations were performed as an independent verification of commercial dosimetry software (BEBIG Plaque Simulator). Excel spreadsheets were constructed to follow the formalism of the AAPM Task Group No. 43. As a software commissioning tool, TG43 seed-based coordinates were reformatted to be compatible with plaque-based BEBIG dose tables for centrally positioned seeds. Plaque central axis doses were also calculated for rings of seeds. Close agreement with BEBIG doses was obtained in both cases. Tailored spreadsheet versions were subsequently created to verify patient treatment plans. Treatment time and dose to a specified central-axis point are calculated for ROPES plaques fully loaded with 1-125 model 6702 seeds. PMID- 11764402 TI - The performance of a NERO 8000 non-invasive x-ray beam analyser when measuring tube voltage under fluoroscopic conditions. AB - A NERO 8000 non-invasive x-ray beam analyser was examined under fluoroscopic conditions with respect to the measurement of tube voltage. An invasive measurement of tube voltage was performed concurrently to test the accuracy of the NERO device over a range of tube voltages and currents. The data indicated that for the NERO 8000 the accuracy of kVp average measurement is dependent on input doserate. With the tube current set to 1 mA the doserates ranged from 2.1 to 6.5 mGy/min over the range of tube voltages measured. The associated kVp average measurement errors ranged from 6 to 28%. At 5 mA the doserates ranged from 20.4 to 66.0 mGy/min and the associated errors ranged from 0 to 3%. A possible explanation for the drop in accuracy of kVp measurements at low doserates is a decreased signal to noise ratio. The kV waveforms from inaccurate measurements appeared noisier than waveforms from more accurate measurements. NERO may be interpreting noise spikes as voltage readings and including them in the kVp average calculations, causing an erroneously high kVp average reading. The data from this experiment suggest that when performing non-invasive measurements of tube voltage accuracy in fluoroscopy mode, the doserate must be taken into consideration. PMID- 11764403 TI - Determination of diamino acids in peptidoglycans from anaerobic bacteria. AB - Peptidoglycans isolated from two Fusobacterium species of anaerobic bacteria were analyzed for constituent amino acids. Hydrolysis conditions were varied to optimize the yield of diamino acids from peptidoglycan. The o-phthalaldehyde derivatives of the diamino acid stereoisomers were separated by high-performance liquid chromatography (OPA-HPLC), and variations in the relative areas of the two peaks noticed during analysis of solid samples were attributed to sampling errors. Co-derivatization/injection experiments using standards of the meso and rac forms separated from commercial mixtures demonstrated that meso-2,6 diaminopimelic acid and meso-lanthionine were peptidoglycan components in Fusobacterium varium and Fusobacterium nucleatum, respectively. The protonated molecules of 2,6-diaminopimelic acid and lanthionine were detected in peptidoglycan hydrolyzates by off-line, flow-injection electrospray mass spectrometry (ESI-MS). In ESI-MS-MS experiments under identical collision-induced dissociation (CID) conditions, peptidoglycan-derived and standard diamino acids exhibited similar fragmentations. Fragmentation pathways are proposed for each diamino acid. The results confirm that the meso forms of two different diamino acids are utilized in the peptidoglycans of Fusobacterium species. PMID- 11764404 TI - Plasma total homocysteine and subarachnoid haemorrhage in a co-factor replete population. AB - Mild hyperhomocysteinaemia is a postulated risk factor for occlusive vascular disease, including stroke. Subarachnoid haemorrhage (SAH) has an annual incidence of 10-20 per 100,000 and accounts for 5-10% of all strokes. Measurement of plasma total homocysteine (tHcy) in a cohort of vitamin B12 and folate replete patients did not reveal any association between tHcy and the aetiology of SAH. PMID- 11764405 TI - Structure-activity relationships in coeliac-toxic gliadin peptides. AB - Computer modelling studies of two groups of biologically-active peptides derived from A-gliadin indicated that the most likely structures were a-helical ones, in the case of serine-containing peptides, and random peptides coil types featuring beta-turns, in the case of proline-rich, tyrosine-containing peptides. The serine containing group of peptides appear to be essentially cytotoxic in animal models of coeliac disease, whilst the tyrosine-containing group have the capacity to initiate damaging immunological reactions in patients with coeliac disease. Both types of activity in coeliac disease are only possible if there is defective digestion of the active peptides, as mucosal digestion studies indicate. In the case of the serine-containing peptides, activity of the peptides is linked to the presence of PSQQ and also probably QQQP motifs. With the tyrosine-containing peptides, sequences such as QQPY and/or QPYP are associated with immunological activity and hence toxicity. PMID- 11764406 TI - The peptides of alpha-aminosuberic acid II. Synthesis of deamino-dicarba-eel calcitonin sequence 1-9. AB - The paper describes the synthesis of Asu6-octapeptide derivatives by condensing two alternative pentapeptide fragments with Asu-containing tripeptides. After partial deprotection these linear peptides compounds are subject to cyclization experiments aimed to give the N-terminal [1-9] sequence of deamino-dicarba-eel calcitonin. This is a key substance for the semi-synthesis of the respective analogues of eel calcitonin. PMID- 11764407 TI - Efficient synthesis of pyrenylalanine. AB - An efficient synthesis of L-3-(1'-pyrenyl)alanine (Pya), a highly fluorescent amino acid, is described. The amino acid was obtained by the classical asymmetric hydrogenation of chiral 1-acetyl-3-pyrenemethylidene-6-methyl-piperazine-2,5 dione. In the proposed improved procedure mild conditions of the synthesis were applied and the final product--N-tertbutoxycarbonyl-pyrenylalanine--was obtained in good yield. Pyrenylalanine, due to its interesting photophysical properties, can be applied as a fluorescent probe in numerous biochemical and conformational studies. PMID- 11764408 TI - Characterization of spermine uptake by Ehrlich tumour cells in culture. AB - Spermine is taken up by Ehrlich ascites tumour cells through a specific, saturable, temperature and energy-dependent transport system with a remarkably low affinity constant for spermine (around 1 microM). In the absence of a potassium ion gradient through the plasma membrane, spermine uptake remains saturable but the value of the Km for spermine is much higher (153 microM). Difluormethylornithine treatment (3 mM for 48h) induces significant increases in Vmax values (up to 9-fold) and changes in the Km values with scarce statistical significance. Among the biogenic amines tested, only spermidine and, partly, agmatine seem to share the same transport system with spermine. No difference is observed in the rate of spermine transport when assays are carried out in the presence of 50-fold excess of ornithine or calcium, or 100-fold excess of glutamine. PMID- 11764409 TI - Activated alumina as an energy source for peptide bond formation: consequences for mineral-mediated prebiotic processes. AB - The catalytic properties of various forms of alumina were tested for alanine dimerization reaction. The catalytic efficiency of alumina depends on the structure, as well as on acid/base properties of the catalyst. The highest yields of Ala2 were achieved on activated alumina with surface of neutral pH (about 3% conversion after 2 weeks). Thermal analysis of Ala + alumina reaction systems shows that the thermal behavior of amino acid changes substantially in contact with the activated surface of the alumina catalyst. The reaction of Ala is detected as being strongly endothermic by differential thermal analysis of pure amino acid (above 250 degrees C). The alanine endothermic reaction is shifted substantially to lower values (below 200 degrees C) and hardly detectable if activated alumina is present. The reaction mechanism of amino acid activation on alumina surface and its significance for mineral-catalyzed prebiotic peptide bond formation are discussed. PMID- 11764410 TI - Neurofilament proteins NF-L, NF-M and NF-H in brain of patients with Down syndrome and Alzheimer's disease. AB - Neurofilaments (NFs) are integral constituents of the neuron playing a major role in brain development, maintenance, regeneration and the pattern of expression for NFs suggests their contribution to plasticity of the neuronal cytoskeleton and creating and maintaining neuronal architecture. Using immune-histochemical techniques the altered expression of NFs in Down syndrome (DS) and Alzheimer's disease (AD) has been already published but as no corresponding systematic immune chemical study has been reported yet, we decided to determine proteins levels of three NFs in several brain regions of DS and AD brain. We evaluated immunoreactive NF-H, NF-M and NF-L levels using Western blotting in brain regions temporal, occipital cortex and thalamus of patients with DS (n = 9), AD (n = 9) and controls (n = 12). We found significantly increased NF-H in temporal cortex (controls: means 0.74+/-0.39 SD; DS: means 3.01+/-2.18 SD) of DS patients and a significant decrease of NF-L in occipital cortex of DS and AD patients (controls: means 1.19+/-0.86 SD; DS: means 0.35+/-0.20; AD: 0.20+/-0.11 SD). We propose that the increase of NF-H in temporal cortex of DS brain is due to neuritic sprouting as observed in immune-histochemical studies. The increase may not be caused by the known accumulation of NFs in plaques, tangles or Lewy bodies due to our solubilization protocol. The decrease of NF-L in occipital cortex of DS and AD patients may well be reflecting neuronal loss. Altogether, however, we suggest that NFs are not reliable markers for neuronal death, a hallmark of both neurodegenerative diseases, in DS or AD. The increase of NF-H in DS or the decrease of NF-L in DS and AD leaves the other NFs unchanged, which points to dysregulation in DS and AD and raises the question of impaired structural assembly of neurofilaments. PMID- 11764411 TI - Conscientious metabolic monitoring on a patient with hyperornithinemia hyperammonemia-homocitrullinuria (HHH) syndrome undergoing anaesthesia. AB - Currently we know not more than 50 patients who show an interesting combination of increased plasma ornithine concentrations, postprandial hyperammonemia, and homocitrullinuria (HHH-syndrome). Since exact knowledge of this severe, although rare syndrome is important for any perioperative or intensive medical treatment concerning therapy and progression of the disease, we report a comprehensive study on a 32-year old woman with this rare multifaceted disorder who had to undergo general anaesthesia. For the first time amino acid status in plasma, urine, cerebrospinal fluid and especially polymorphonuclear leucocytes, which in the investigation showed to be valuable tool for evaluating amino acid metabolism in nucleated cells in HHH-syndrome, and further important pathophysiologic indicators of cellular and metabolic function have been conscientiously investigated and compared. The pathophysiological repercussions of our results as well as the recommendations for conscientious therapeutical management are discussed. PMID- 11764412 TI - L-Canavanine: a higher plant insecticidal allelochemical. AB - L-Canavanine, L-2-amino-4-(guanidinooxy)butyric acid, is a potentially toxic nonprotein amino acid of certain leguminous plants. Many species are prolific canavanine producers; they divert enormous nitrogen resource to the storage of this single natural product. Canavanine, a highly effective protective allelochemical, provides a formidable chemical barrier to predation and disease. The accumulated experimental evidence leaves little doubt that the key element in the ability of canavanine to function as an effective protective allelochemical is its subtle structural mimicry of arginine which makes it an effective substrate for amino acid activation and aminoacylation, and its marked diminution in basicity relative to arginine which mediates the production of structural aberrant, dysfunctional canavanyl proteins. The biological burdens of canavanyl protein formation by canavanine-treated Manduca sexta larvae were carried throughout their remaining life cycle. Protein-based sequestration of canavanine prevented turnover and clearance of the free amino acid, and undoubtedly contributed significantly to the antimetabolic character of this protective allelochemical. PMID- 11764413 TI - Colorectal carcinogenesis. AB - Colorectal carcinogenesis is a multi-step process during which genetic and epigenetic events determine the transition from a normal cell to a malignant cell. In the past decade, intensive research led to the identification of two types of colorectal cancers that are distinct by their carcinogenesis process. The first group, named LOH (Loss of Heterozygosity) type, is characterized by allelic losses of tumor suppressor genes. The second group, called MSI (Microsatellite Instability) type, is characterized by genetic instability at microsatellite loci. In addition, recent studies suggest the four different signaling pathways, Wnt/Wingless pathway, K-ras pathway, TGF-beta pathway and p53 pathway, could be implicated in tumor progression. In this review we discuss the development of colorectal cancer on the basis of molecular biology and recent advances in research of the colorectal cancer. PMID- 11764414 TI - Accommodative microfluctuation in asthenopia caused by accommodative spasm. AB - BACKGROUND: Although many patients complain of eye fatigue caused by accommodative spasm, there have been no reports of a good objective examination method to diagnose it. PURPOSE: The spectral power of the high frequency component of the accommodative microfluctuation (spectral power of HFC) differs according to the constrictive degree of the accommodation. In this paper, we expatiated upon our previously reported analyzing processes of the spectral power of HFC, and we investigated the relationship between normal subjects and subjects with asthenopia. METHOD: The accommodative microfluctuation were recorded when the subjects were looking at a stable target. The waves of the accommodative microfluctuation were analyzed by FFT. RESULTS: The spectral power of HFC for the distant target was 50-60 in the subjects with normal vision, but it was higher in the subjects with asthenopia. CONCLUSION: Our results suggested that the ciliary muscle was also actively working in asthenopia caused by accommodative spasm even if the patient was looking at a distant target. PMID- 11764415 TI - Spinal evoked potentials following transcranial magnetic stimulation. AB - Motor evoked potentials by magnetic stimulation is less invasive and causes no pain as opposed to high current electric stimulation. However, the distribution of the magnetic field generated by the round coil has not been fully studied. In this report, we mapped the extent of the magnetic induction flux density, and then the evoked potentials from the spinal cord were investigated by transcranial magnetic stimulation. We also examined the origin of the evoked potentials obtained by the magnetic stimulation. The following results were obtained. The magnetic induction flux density was at its maximum at the edge of the coil. The potentials consisted of a first negative wave and subsequent multiphasic waves. The first negative wave was similar to a response of the subcorticospinal tract in the lower brain stem, while the subsequent multiphasic waves were similar to those of the pyramidal tract. Although magnetic stimulation has certain advantages over electric stimulation, several problems remain to be solved for the monitoring of motor functions in the clinical settings. PMID- 11764416 TI - Immune thrombocytopenia in an elderly patient treated successfully by pulse therapy with cyclophosphamide. AB - Thrombocytopenia due to immune mechanisms is rare and difficult to manage in elderly patients. We describe a case of an 89-year-old female with severe immune thrombocytopenia (ITP) who rapidly improved by pulse therapy with cyclophosphamide. She was admitted to our hospital because she had arthralgia in both sides of her femoral region since January 1999, aphthous stomatitis and ecchymosis of the leg since April 1999, and bloody phlegm in July 1999. On admission, her peripheral blood count revealed severe thrombocytopenia (0.1 x 10(4)/microl). Her megakaryocyte count from bone marrow was increased to 512/microl without abnormal cells. Systemic lupus erythematosus was suspected because of strong positive protein in the urine in addition to the clinical and hematological findings described above, but she was negative for all the autoantibodies examined. Finally, she was diagnosed as having ITP on the basis of high platelet associated immunoglobulin G in addition to hematological and physical findings and she was treated with prednisolone. It was difficult to maintain her platelet count with only prednisolone, but 600 mg of cyclophosphamide rapidly increased her platelet count in spite of tapering the prednisolone. In September 2000, her platelet count was kept within normal limits by administration of 15 mg/day of prednisolon. It is suggested that immunosuppressive therapy for ITP using high-dose cyclophosphamide is useful in elderly patients as well as in juvenile adult patients. PMID- 11764417 TI - Chromosomal changes after surgery for joint replacement. PMID- 11764418 TI - The use of the Internet by orthopaedic outpatients. PMID- 11764419 TI - Reconstruction does not reduce tibial translation in the cruciate-deficient knee an in vivo study. AB - We have assessed the effectiveness of reconstruction of the anterior cruciate ligament (ACL) in reducing functional tibial translation (TT). The gait of 11 ACL deficient patients was studied using Vicon equipment before and after surgery. Measurements of the angle between the patellar tendon and the long axis of the tibia were obtained in order to calculate TT in the sagittal plane relative to the uninjured limb during standing and walking. Before surgery, patients did not show abnormal TT on the injured side, but after surgery significant anterior TT was found in the operated limb for every parameter of gait. Abnormal anterior TT occurring during activity does not seem to be reduced by reconstruction; rather, it increases. It may be that the increased translation results from relaxation of excess contraction of the hamstring muscles, since compensatory muscle activity no longer is required in a reconstructed knee. The reduction of TT may not be an appropriate objective in surgery on the ACL. PMID- 11764420 TI - Effects of reconstruction of the anterior cruciate ligament on voluntary activation of quadriceps femoris a prospective twitch interpolation study. AB - The loss of full muscle activation contributes to weakness of the quadriceps muscle in patients with deficiency of the anterior cruciate ligament (ACL). We examined whether a deficit of voluntary activation (VA) of the quadriceps muscle can be reversed by reconstruction of the ACL and assessed its influence on muscle strength and clinical parameters. We evaluated 12 male subjects with an isolated tear of the ACL and 12 matched control subjects before operation and two years after reconstruction of the ACL. Assessment included measurements of isometric knee-extension torque at maximal voluntary contraction (MVC force), knee stability tests, the International Knee Ligament Standard Evaluation Form and the Tegner activity score. A sensitive method of twitch interpolation was used to quantify the VA and to calculate true muscle force. Before operation we found a deficit of VA on both the injured (mean +/- SEM 74.9 +/- 3.5%) and the uninjured side (74.6 +/- 3.0%) in comparison with the control group (91 +/- 0.9%). Two years after reconstruction of the ACL the VA improved significantly on both sides but remained less than that of the controls. Correlation analysis revealed an improvement of the VA in patients who returned to a higher level of activity. The deficit of true muscle force, however, persisted regardless of the clinical outcome and ligament stability. PMID- 11764421 TI - Open-wedge osteotomy of the proximal tibia with hemicallotasis. AB - Conventional high tibial osteotomy for losteoarthritis of the medial compartment of the knee with closed-wedge or dome osteotomy (DMO) may produce shortening of the patellar tendon and loss of inclination of the proximal tibial plateau or of the offset of the tibial condyle relative to its bony axis. This can make subsequent total knee arthroplasty technically demanding. We undertook a prospective study comparing these changes after DMO with those after using open wedge osteotomy hemicallotasis (HCO). A total of 50 knees with arthritis of the medial compartment in 46 consecutive patients was randomly allocated to either DMO or HCO. There were no significant differences between the groups with regard to age, gender, femorotibial angle before operation or the angle of correction. Radiological studies showed that HCO caused little change in the length of the patellar tendon or the inclination angle of the tibial plateau, while after DMO both gradually decreased. The degree of tibial condylar offset increased in both groups, but less so in the HCO group. PMID- 11764422 TI - Ulceration of the lower leg after total knee replacement a five-year review. AB - Ulceration of the lower leg is considered to be a hard' clinical endpoint of venous thrombosis. Total knee replacement (TKR) is a significant risk factor for venous thrombosis of the leg and therefore potentially for ulceration. We sent a postal questionnaire to 244 patients at a minimum of five years after TKR enquiring about the development of ulceration since their TKR. The overall incidence of ulceration, both active and healed, was 8.67% which is similar to that in the age-matched general population (9.6% to 12.6%), as was the prevalence of active ulceration. We also identified no clear association between venographically-confirmed postoperative deep-venous thrombosis (DVT) and the incidence and prevalence of ulcers at five years. We suggest that after TKR DVT is not a significant risk factor for ulceration of the leg and that perioperative chemical thromboprophylaxis may not be justified on these grounds. PMID- 11764423 TI - Surgical dislocation of the adult hip a technique with full access to the femoral head and acetabulum without the risk of avascular necrosis. AB - Surgical dislocation of the hip is rarely undertaken. The potential danger to the vascularity of the femoral head has been emphasised, but there is little information as to how this danger can be avoided. We describe a technique for operative dislocation of the hip, based on detailed anatomical studies of the blood supply. It combines aspects of approaches which have been reported previously and consists of an anterior dislocation through a posterior approach with a 'trochanteric flip' osteotomy. The external rotator muscles are not divided and the medial femoral circumflex artery is protected by the intact obturator externus. We report our experience using this approach in 213 hips over a period of seven years and include 19 patients who underwent simultaneous intertrochanteric osteotomy. The perfusion of the femoral head was verified intraoperatively and, to date, none has subsequently developed avascular necrosis. There is little morbidity associated with the technique and it allows the treatment of a variety of conditions, which may not respond well to other methods including arthroscopy. Surgical dislocation gives new insight into the pathogenesis of some hip disorders and the possibility of preserving the hip with techniques such as transplantation of cartilage. PMID- 11764424 TI - Evidence for the validity of a patient-based instrument for assessment of outcome after revision hip replacement. AB - The Oxford hip score (OHS) is a patient-based instrument for assessment of outcome which is often used after total hip replacement, and the EuroQol 5D (EQ5D) is a patient-based generic questionnaire for health assessment. In an analysis of the outcome at one year of 609 revision hip replacements (RHRs), we compared the OHS and EQ5D scores, postoperative patient satisfaction and change in pain. About 25% of the operations were repeat RHRs. At one year, 57% of patients were very pleased with their operation. The correlation between preoperative and postoperative scores and change scores for the OHS and EQ5D was high. For both instruments the effect sizes were large, but the greater effect size of the OHS suggests that it is particularly sensitive to improvements after RHR. The effect scores of the OHS declined with the number of previous RHRs, while those for the EQ5D seemed less sensitive. Our results confirm the value of the OHS in assessing outcome after RHR. PMID- 11764425 TI - Prevention of pulmonary embolism by a foot sole pump. AB - We carried out a prospective, randomised study of 62 patients to determine the efficacy of a foot sole pump (the A-V Impulse System) for the prevention of pulmonary embolism (PE) after hip surgery. PE was assessed by pulmonary perfusion scintigraphy before and after operation. We defined a PE as any new scintigraphic defect which was larger than a bronchopulmonary segment. The incidence of PE was 55% in the control group and 21% in the treatment group. The foot sole pump significantly reduced the incidence of PE (p = 0.008) and we encountered no side effects from its use. PMID- 11764426 TI - The effect of spinal fusion on the long-term outcome of idiopathic scoliosis. A case-control study. AB - We have investigated the effect of multisegmental spinal fusion on the long-term functional and radiological outcome in patients with scoliosis. We compared these patients both with those whose spine had not been fused, and with a control group. We studied 68 patients with idiopathic scoliosis (34 operative and 34 non operative) who had been followed up for a minimum of five years after treatment. They were matched for age (mean 44 years) and Cobb angle (mean 54 degrees) at follow-up. An age- and gender-matched control group of 34 subjects was also recruited. All participants completed a questionnaire to assess spinal function and to grade the severity of back pain using a numerical rating scale. Radiographs of the spine were taken in the patients with scoliosis and lumbar degenerative changes were recorded. The spinal function scores for the patients with scoliosis who had had a fusion were similar to those who had not. Both scoliosis groups, however, had lower scores than the control group (p < 0.001). The frequency and severity of back pain were lower for patients with scoliosis and fusion than for those without, but higher for both scoliosis groups compared with the control group. Radiographs showed similar degenerative changes in both scoliosis groups. PMID- 11764427 TI - Lumbosacral transitional vertebrae and nerve-root symptoms. AB - Transitional vertebrae (TV) may be one of the risk factors for lumbar disc herniation. It is not clear, however, whether the presence of TV can affect the development of nerve-root symptoms. Our aim was to clarify this relationship. A total of 501 patients with lumbar degenerative disease and nerve-root symptoms was studied in respect of their level and the presence of TV. As a control group, 508 patients without low back pain or nerve-root symptoms were studied to establish the incidence of TV. In patients with disc herniation, the incidence was statistically higher and the mean age lower in patients with TV than in those without. In most patients, the symptomatic disc level was just above the TV. Similarly, in those with stenosis of the spinal canal without spondylolisthesis, the symptomatic disc level was most commonly just above the TV. PMID- 11764428 TI - Fractures of the pubic rami. Epidemiology and five-year survival. AB - We reviewed 286 consecutive patients with a fracture of a pubic ramus. The overall incidence was 6.9/100,000/year in the total population and 25.6/100,000/year in individuals aged over 60 years. The mean age of the patients was 74.7 years and 24.5% suffered from dementia. Women were affected 4.2 times more often than men. After injury, geriatric rehabilitation was frequently required and although most surviving patients returned to their original place of residence, their level of mobility was often worse. The overall survival rates at one and five years were 86.7% and 45.6%, respectively. Multiple logistic regression analysis showed that age and dementia were the only independent significant factors to be predictive of mortality (p < 0.05). Patients with a fracture of a pubic ramus had a significantly worse survival than an age-matched cohort from the general population (log-rank test, p < 0.001), but this was better than patients with a fracture of the hip during the first year after injury, although their subsequent mortality was higher. Five years after the fracture there was no significant difference in survival between the two groups. PMID- 11764429 TI - Latropathic injuries of peripheral nerves. AB - This is a retrospective study of 612 cases of iatropathic injury to peripheral nerves seen in one tertiary referral unit between 1991 and 1998. A total of 291 patients was subsequently operated on to explore the nerve lesion. The most common presenting symptom was pain, which often masked underlying loss of function. The delay in diagnosis was up to 40 months. The findings at operation were analysed according to the type of nerve damaged, the nature of the injury and the referring specialty. Some of the more common causal operations and procedures are discussed. Preventive measures are listed, and early diagnosis and treatment are recommended. PMID- 11764430 TI - Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence. AB - We considered whether a positive margin occurring after resection of a soft tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection. PMID- 11764431 TI - Modular prosthetic replacement of the proximal femur after resection of a bone tumour a long-term follow-up. AB - We describe 25 patients who were treated for a tumour of the proximal femur by resection and replacement with an uncemented, bipolar, modular prosthesis. When followed up after more than ten years four prostheses (16%) had required revision. Two joints showed wear and another necrosis of the acetabulum. One patient with loosening of the stem had been treated by radiotherapy to the femur. Articular cartilage seemed to be a reliable barrier to acetabular wear. Very few signs of the formation of particulate debris were observed. The most obvious feature in the bone-stem relationship was stress shielding, seen as osteoporosis of the proximal part of the femur around the stem in 68%. Functional activity was satisfactory in 68% of the patients. A better system of reattachment of the soft tissues is needed to avoid pain and a persistent limp. PMID- 11764432 TI - Bilateral hip surgery in severe cerebral palsy a preliminary review. AB - When cerebral palsy involves the entire body pelvic asymmetry indicates that both hips are 'at risk'. We carried out a six-year retrospective clinical, radiological and functional study of 30 children (60 hips) with severe cerebral palsy involving the entire body to evaluate whether bilateral simultaneous combined soft-tissue and bony surgery of the hip could affect the range of movement, achieve hip symmetry as judged by the windsweep index, improve the radiological indices of hip containment, relieve pain, and improve handling and function. The early results at a median follow-up of three years showed improvements in abduction and adduction of the hips in flexion, fixed flexion contracture, radiological containment of the hip using both Reimer's migration percentage and the centre-edge angle of Wiberg, and in relief of pain. Ease of patient handling improved and the satisfaction of the carer with the results was high. There was no difference in outcome between the dystonic and hypertonic groups. PMID- 11764433 TI - Retrosternal displacement after physeal fracture of the medial clavicle in children treatment by open reduction and internal fixation. AB - Retrosternal displacement of the medial aspect of the clavicle after physeal fracture is rare. We treated six patients with this injury between 1995 and 1998, all as an emergency in order to avoid complications associated with compression of adjacent mediastinal structures. Attempted closed reduction was undertaken, but all required open reduction and internal fixation using a wire suture. There were no associated complications. Five were reviewed clinically and radiologically at a minimum of one year after operation. All had regained full use of the affected arm without pain and had resumed their preinjury level of activity including sports. Follow-up radiographs showed union in the anatomical position in all patients. We recommend attempted closed reduction in the operating room, followed, if necessary, by open reduction. Internal fixation after open reduction gives stable fixation with minimal morbidity. PMID- 11764434 TI - Simple treatment for torus fractures of the distal radius. AB - Torus (buckle) fractures of the distal radius are common in childhood. Based on the results of a postal questionnaire and a prospective, randomised trial, we describe a simple treatment for this injury, which saves both time and money. Over a six-month period, we randomised 201 consecutive patients with this injury to treatment with either a traditional forearm plaster-of-Paris cast or a 'Futura type' wrist splint. All patients were treated for a period of three weeks, followed by clinical and radiological review. There was no difference in outcome between the two groups, and all patients had a good result. Only one patient did not tolerate the splint which was replaced by a cast. The questionnaire showed a marked variation in the way in which these injuries are treated with regard to the method and period of immobilisation, the number of follow-up visits and radiographs taken. We suggest that a 'Futura-type' wrist splint can be used to treat these fractures. The patient should be reviewed on the following day to confirm the diagnosis and to give appropriate advice. There is no evidence that further follow-up is required. This simple treatment has major benefits in terms of cost and reduction of the number of attendances. PMID- 11764435 TI - Bicipetal tenodesis for anterior subluxation of the superior tibiofibular joint. AB - A technique for stabilising the superior tibiofibular joint using an autogenous biceps graft passed through a tibial tunnel is described. The common peroneal nerve should be decompressed and the lateral inferior genicular artery protected. The technique proved to be safe and effective in two patients who were followed for at least two years. PMID- 11764436 TI - Osteofibrous dysplasia of the ulna. AB - Osteofibrous dysplasia is a rare condition usually ffecting the tibiae and fibulae of males in the first two decades of life. Involvement at the ulna has also been reported in some cases. We describe an extensive, rapidly progressive lesion of the ulna in a three-year-old girl. The progression of the disease accelerated after a local marginal removal, and required extensive resection of the ulna with reconstruction using a fibular autograft. The particular features of this case are the change in the aggressive nature of the condition, which has not been previously reported. We believe that this is only the second recorded case of histologically proven involvement of the ulna. PMID- 11764437 TI - Isolation of polyacetal wear particles from periprosthetic tissue of isoelastic femoral stems. AB - We analysed revised Mathys isoelastic polyacetal femoral stems with stainless steel heads and polyethylene acetabular cups from eight patients in order to differentiate various types of particle of wear debris. Loosening of isoelastic femoral stems is associated with the formation of polyacetal wear particles as well as those of polyethylene and metal. All three types of particle were isolated simultaneously by tissue digestion followed by sucrose gradient centrifugation. Polyacetal particles were either elongated, ranging from 10 to 150 microm in size, or shred-like and up to 100 microm in size. Polyethylene particles were elongated or granules, and were typically submicron or micron sized. Polyacetal and polyethylene polymer particles were differentiated by the presence of BaSO4, which is added as a radiopaque agent to polyacetal but not to polyethylene. This was easily detectable by back-scattered SEM analysis and verified by energy dispersive x-ray analysis. Two types of foreign-body giant cell (FBGC) were recognised in the histological specimens. Extremely large FBGCs with irregular polygonal particles showing an uneven, spotty birefringence in polarised light were ascribed to polyacetal debris. Smaller FBGCs with slender elongated particles shining uniformly brightly in polarisation were related to polyethylene. Mononucleated histiocytes containing both types of particle were also present. Our findings offer a better understanding of the processes involved in the loosening of polyacetal stems and indicate why the idea of 'isoelasticity' proved to be unsuccessful in clinical practice. PMID- 11764438 TI - Neurones in the dorsal root ganglia of T13, L1 and L2 innervate the dorsal portion of lower lumbar discs in rats. A study using diI, an anterograde neurotracer. AB - Based on a study using a retrograde neurotracer, we have previously found that the dorsal portion of the L5/6 disc in the rat is multisegmentally innervated by dorsal root ganglia (DRG) from the level of T13 to L6, and that sensory nerve fibres from DRG of T13, L1 and L2 pass through the paravertebral sympathetic trunks. In this study in newborn rats, we injected crystals of 1,1'-dioctadecyl 3,3,3',3'-tetramethylinedocarbocyanine perchlorate (DiI) into the DRG of T13, L1 and L2 and showed DiI-labelled sensory nerve fibres in the dorsal portion of the discs from the level of T13/L1 to L5/6. Our results show that the dorsal portion of the lumbar discs is innervated by the DRG from levels T13 to L2. PMID- 11764439 TI - A retrieval study of capital hip prostheses with titanium alloy femoral stems. AB - We have examined 26 retrieved, failed titanium-alloy femoral stems. The clinical details, radiological appearances and the histology of the surrounding soft tissues in each patient were also investigated. The stems were predominantly of the flanged design and had a characteristic pattern of wear. A review of the radiographs showed a series of changes, progressive with time. The first was lateral debonding with subsidence of the stem. This was followed by calcar resorption and fragmentation or fracture of the cement. Finally, osteolysis was seen, starting with a radiolucency at the cement-bone interface and progressing to endosteal cavitation. Three histological appearances were noted: granulomatous, necrobiotic and necrotic. We suggest that an unknown factor, possibly related to the design of the stem, caused it to move early. After this, micromovement at the cement-stem interface led to the generation of particulate debris and fracture of the cement. A soft-tissue reaction to the debris resulted in osteolysis and failure of fixation of the prostheses. PMID- 11764440 TI - Oral vitamin C attenuates acute ischaemia-reperfusion injury in skeletal muscle. AB - Ischaemia-reperfusion injury (IRI) is caused by endothelial and subendothelial damage by neutrophil-derived oxidants. Vitamin C is an antioxidant which attenuates endothelial injury after IRI. Our aim was to evaluate the effect of oral vitamin C in the prevention of IRI in skeletal muscle. We used a model of cross-clamping (3 hours) and reperfusion (1 hour) of the cremaster muscle in rats. Muscle function was assessed electrophysiologically by electrical field stimulation. Infiltration by neutrophils was determined by the activity of tissue myeloperoxidase (MPO) and tissue oedema by the wet-to-dry ratio. Neutrophil respiratory burst activity was measured in control animals and groups pretreated with vitamin C. IRI significantly decreased muscle function and increased muscle neutrophil MPO activity and muscle oedema. Pretreatment with vitamin C preserved muscle function and reduced tissue oedema and neutrophil infiltration. Neutrophil respiratory burst activity was reduced in the group treated with vitamin C compared with the control group. We conclude that pretreatment with oral vitamin C protects against acute muscle IRI, possibly by attenuating neutrophil respiratory burst activity. PMID- 11764441 TI - How should orthopaedic surgeons respond to unsolicited e-mail? PMID- 11764442 TI - The distress and risk assessment method (DRAM). PMID- 11764443 TI - Fractures involving splitting of the humeral head. PMID- 11764444 TI - Sample size and statistical power of randomised, controlled trials in orthopaedics. PMID- 11764445 TI - [The journal and the readers in the flow of medical information]. PMID- 11764446 TI - [Mitral valve prolapse as the cause of brain infarction]. PMID- 11764447 TI - [Chlamydias--the Cinderella story of infectious diseases]. PMID- 11764448 TI - [Deeper roots of superficial eye diseases]. PMID- 11764449 TI - [Eating disorders, thinness and infertility]. PMID- 11764450 TI - [Imaging the ear]. PMID- 11764451 TI - [Compliance with treatment in schizophrenia and mood disorders]. PMID- 11764452 TI - [Why does a child with enuresis have a seizure?]. PMID- 11764453 TI - [Parasites--tiny but unpleasant companions at home and in the daycare]. PMID- 11764454 TI - [How should a clip and a coil be called in Finnish?]. PMID- 11764456 TI - [Targeted drugs against influenza--how will this affect the epidemics?]. PMID- 11764457 TI - [What should a doctor know about viral diagnostics?]. PMID- 11764458 TI - [Antiviral agents and the practicing physician]. PMID- 11764459 TI - [Common cold and its complications]. PMID- 11764460 TI - [Nephropathia epidemica and other hanta virus infections: how rodents' viruses cause disease in human?]. PMID- 11764461 TI - [HIV epidemic in intravenous drug users--is Finland behind or ahead of other Western countries?]. PMID- 11764462 TI - [Prevention, diagnostics and treatment of virus hepatitis]. PMID- 11764463 TI - [Are food poisonings caused by viruses?]. PMID- 11764464 TI - [Delayed effects of viral infections]. PMID- 11764465 TI - [What should be on the list of elimination after polio virus?]. PMID- 11764466 TI - [How do viruses avoid the host defense system?]. PMID- 11764467 TI - [Is there any sense to distribute free needles?]. PMID- 11764468 TI - [Self-management of the anticoagulant therapy?]. PMID- 11764469 TI - [Hypoglycemia in diabetic children]. PMID- 11764470 TI - [Magnetic resonance cholangiography]. PMID- 11764471 TI - [Portfolio as a method of learning in medicine]. PMID- 11764472 TI - [Pusher syndrome]. PMID- 11764473 TI - [Late adverse effects of the Hodgkin's disease therapy]. PMID- 11764474 TI - [Drug therapy of the lactating mother]. PMID- 11764475 TI - [Anticoagulant treatment of patient with the substitute heart valve]. PMID- 11764476 TI - [On teaching the evolution theory]. PMID- 11764477 TI - [Trends in development of military surgery in armed conflicts of the second half of XX century]. PMID- 11764478 TI - [Rendering anesthesiological and resuscitation care to wounded by a medical reinforcement group in an armed conflict]. AB - The authors describe the aims and content of anesthesiologic and reanimatologic care of the medical reinforcement group in the medical institution of the 1st echelon of specialized care. Basing on the experience of treatment of 825 casualties with gunshot injuries the rational methods of anesthesia and intensive care are shown including the prolonged controlled ventilation, infusion transfusion therapy, early enteral nutrition. The main causes of lethal outcomes are analyzed. The conclusion was made that during counter-terrorist operations it is reasonable to include anesthesiologists and reanimatologists into the medical reinforcement group. PMID- 11764479 TI - [Surgical tactics "damage control" in the treatment of severe combat injuries and trauma]. PMID- 11764480 TI - [Rendering surgical care to wounded with neck wounds in an armed conflict]. AB - The results of rendering of the medical care (the first aid, qualified and specialized) obtained in 172 servicemen with neck injuries who stayed in Republic of Chechnya during the period from 09.08.1999 to 28.07.2000 were analyzed. Basing on the results of analysis and experience of casualties' treatment the authors discuss the problems of sequence and volume of surgical care in this group of casualties with reference to available medical evacuation system, surgical tactics at the stage of specialized care. They also consider the peculiarities of operative treatment of the casualties with neck injuries. PMID- 11764482 TI - [Infectious complications of severe trauma: achievements and problems]. AB - On the base of treatment results obtained in 2000 casualties the pathogenically substantiated classification of infectious complications of the injuries and traumas was proposed. The principles of classification are in conformity with modern ideas connected with the conception of systemic inflammatory response, the theory of general adaptation and the concept of traumatic disease. The classification determines the purposeful diagnostic tactics and provides the preventative therapy of traumas' infectious complications. Selection of special direction in the surgery of injuries in order to solve the problem of traumas' infectious complications in scientific, methodical and practical aspects is substantiated. First of all it is creation of specialized centers that provide the introduction into medical practice of the modern conception of traumas' infectious complications. PMID- 11764481 TI - [Establishment, development, and further improvement of the support system for the medical treatment and evacuation of troops]. PMID- 11764484 TI - [Efficacy of rispolept and zyprexa in the treatment of patients with schizophrenia]. PMID- 11764483 TI - [Current methods of the multiple sclerosis treatment]. PMID- 11764485 TI - [Modern means of anti-Helicobacter therapy]. PMID- 11764486 TI - [KST-1 kit: the use in the surgical treatment of victims with severe combined wounds and trauma]. PMID- 11764487 TI - [The world first department and clinic of military field surgery]. AB - The authors show the main stages of field surgery formation in our country emphasizing the merits of V. Villie, N. Pirogov, V. Oppel, the history of field surgery department beginning from the day of its creation (August 8, 1931) till our days. The main scientific directions of the department's work are shown. It is noted that the modern period of its work is connected with revision of some states of military-and-medical doctrine. The data of the collective's practical work are presented. PMID- 11764488 TI - [Problems of survival from alimentary dystrophy during Leningrad blockade (on the 60th anniversary of the beginning of Leningrad blockade)]. PMID- 11764489 TI - [65 years to Chebarkul'sk military sanatorium]. PMID- 11764490 TI - [Effect of agroclavine on conditional active and passive avoidance responses in mice]. AB - The effect of agroclavine, a compound belonging to the group of ergot alkaloids, on the active and passive avoidance habit learning and retrieval in mice was studied. It was found that agroclavine violated the retention of both habit types, while changing neither the learning rate nor the retrieval efficacy. The drug effect was retained for three weeks after administration. It was suggested that agroclavine probably disturbs the short- to long-term memory transformation. PMID- 11764491 TI - [Effects of paracetamol and naproxen on pain syndromes of various genesis]. AB - A comparative study of the effects of two nonsteroidal antiinflammatory drugs paracetamol and naproxen on the pain syndrome models of various etiology showed that paracetamol is more effective in the case of spinal and neuropathic pain syndromes (in which the leading pathogenic mechanisms are related to the formation of hyperactive neuron aggregates in the central nociceptive structures). Naproxen was effective in the case of adjuvant arthritis, for which the main development mechanism is related to the accumulation of inflammation mediators in tissues. It is concluded that special features of the pathogenic therapy of various pain syndromes are determined by the character of prostaglandin participation in the pathological process. PMID- 11764492 TI - [Comparative characteristics of A1-receptor agonists as neuroprotective agents]. AB - Comparative characteristics of a series of selective A1 agonists influencing the complex global cerebral ischemia (CGCI) are presented and the optimum conditions for realization of the neuroprotective effect are selected. The degree of the neuroprotective action blocking by theophylline and 8-cyclopentyl-1,3 dipropylxanthine (DPCPX) decreases in the following order: CPA CHA ADAC. The A1 receptor agonists exhibit both direct action upon brain (maximum for ADAC) and a peripheral mechanism (especially pronounced for CPA). There is a close correlation between the neuroprotective activity of the A1-receptor agonists and their hypothermal effect. It is suggested that the hypothermal action plays an important part in the neuroprotective activity of the A1-receptor agonists. PMID- 11764493 TI - [Participation of K(ATP)-channels in cardioprotective effect of mu-opioid receptor agonists in acute ischemia and reperfusion of the isolated heart]. AB - Preliminary administration of the mu-opioid receptor (mu-OR) agonist DAMGO (0.1 mg/kg) 15 min before heart isolation led to attenuation of the postischemic systolic and diastolic contractility dysfunction in isolated perfused rat heart. In addition, the mu-OR decreased creatine kinase (CK) release from the heart during the postischemic period, which was indicative of an increase in the sarcolemma tolerance to reperfusion injury. This protective effects are mediated by KATP channel activation. These data show that the mu-OR stimulation in vivo increases, by means of the KATP channel activation, the cardiac tolerance to the ischemia and reperfusion injury in vitro. Pretreatment with mu-OR agonists DAMGO or DALDA in vitro (0.5 mg/liter, 15 min prior to ischemia) exacerbated the postischemic contractility dysfunction of myocardium and did not affect the CK release. It is concluded that the protective effect of mu-OR simulation in vivo is mediated by the activation of these receptors localized outside the heart, probably with an unknown circulating humoral factor. PMID- 11764494 TI - [Anti-arrhythmia effects of enkephalinase inhibitors]. AB - The intravenous pretreatment with enkephalinase inhibitors KB 101 and acetorphan increased the heart resistance to the arrhythmogenic action of adrenaline (epinephrine), is related to activation of the delta-opioid receptors by endogenous enkephalins. At the same time, the mu-receptors and their endogenous agonists play an insignificant role in development of the antiarrhythmic effect of acetorphan. The enkephalinase inhibitors are a promising group of compounds for the development of new antiarrhythmic drugs, because these agents, in contrast to opiates, do not lead to narcotic addiction. PMID- 11764495 TI - [Effect of a novel antimigraine preparation tropoxin on EEG of MR and MNRA rats]. AB - Effect of the new antimigraine drug tropoxin on the EEG profile was studied in MR and MNRA rats with genetically determined high and low levels of emotionality, respectively. In MR rats, tropoxin decreased the number of the bioelectric activity parameters changed by the stressor action (0.9% NaCl, i.p.). The drug reduced the spectral power in the EEG delta band, and increased that in the theta, beta-1, and beta-2 bands. This was evidence of the central stimulating action and the possible enhancement of the exploratory activity. In MNRA rats no changes in bioelectric activity were observed in the low-frequency delta and theta bands, while the spectral power in the beta-1, and beta-2 bands showed a decrease. It was concluded that a neural component is present in the mechanism of the tropoxin action, which may play an important part in the therapeutic effect of the new drug. PMID- 11764496 TI - [Myelotoxicity of a plant cytostatic preparation etoposide]. AB - The myelotoxicity and the hemopoiesis recovery effect of etoposide, an antitumor preparation of the podophyllotoxin group, were experimentally studied on mice. It was found that the main role in the hemopoiesis recovery after etoposide administration is related to accelerated proliferation and increased differentiation of the hemopoietic precursor cells. PMID- 11764497 TI - [Effect of mexidol on clinical and biochemical parameters of perinatal hypoxia in newborn children]. AB - A complex prospective clinical and biochemical study was carried out in a group of 252 children with perinatal encephalopathy in dynamics during the 1st year of their life. The state of the lipid peroxidation (LPO) process, antioxidant system, and the phospholipid content of thrombocyte membranes were studied. Activation of the LPO process and a decrease in the antioxidant resistance level were observed. The efficacy of the antioxidant drug mexidol in infants was investigated for intravenous drug administration in a daily dose of 0.1-0.2 ml/kg over a 10-day period. The results confirmed good efficacy of the antioxidant therapy with mexidol in children with perinatal CNS disturbances. PMID- 11764498 TI - [Antitoxic properties of hepazan--a novel inducer of microsomal enzyme system]. AB - The antitoxic properties of hepazan (dihydrothiazolexanthine), a new inductor of the microsomal enzyme system (MES) of liver were studied in white mice with the MES disorder induced by P. Aeruginosa toxin. It was found that hepazan not only eliminates the toxin-induced depression, but also decreases the toxic effects of ketoconazole, digoxin, and propranolol under the toxinemia conditions. PMID- 11764499 TI - [Effect of ethanol on methanol immunotoxicity]. AB - The results of experiments on Wistar rats under acute methanol poisoning conditions (1 LD 50) showed that ethanol serves as an antidote of methanol. Ethanol reduces nonspecific resistance of the organism and decreases activity of the native killer cells, antibody production mainly with respect to the T dependent antigen, antibody-mediated cell cytotoxicity, and the formation of delayed type hypersensitivity. PMID- 11764500 TI - [Immunity induced by immunomodulators during echinococcal immunosuppression]. AB - The echinococcal immunosuppression induced in experimental mice by a human parasite strain is accompanied by immunosuppression, whereby the administration of immunomodulants favors normalization of the cell and humoral immunity chains. Among a series of preparations studied, the best results were obtained for polyoxidonium: in the case of immunosuppression induced by cyclophosphan, polyoxidonium administration led normalization of the cell and humoral immunity and the phagocytosis of neutrophils and macrophages. PMID- 11764501 TI - [Use of tactivin and imunofan for the treatment of patients with endometrial carcinoma]. AB - Immunofan and tactivin, employed as a means of immunological correction in the complex treatment of adenocarcinoma, decrease the onset frequency of radiation induced complications and exhibit a pronounced immunocorrector effect. This was indicated by increasing level of lymphocytes (including CD3+, CD4+, CD8+, and CD19+), helper coefficient (CD4+/CD8+), and phagocyte activity of neutrophils, as well as by the tendency to normalization of the HCT-test results. Immunofan somewhat exceeds tactivin in the efficacy of endometrium adenocarcinoma treatment. PMID- 11764502 TI - [Anti-inflammatory effect of dichlotazole]. AB - Experiments on various animals showed that dichlotazole, a new triazole derivative, possesses a high antiinflammatory activity and low toxicity. The mechanism of the antiphlogistic effect of dichlotazol is due to its antagonism with respect to mediators of the inflammatory process and the ability of suppressing the increased permeability of capillaries. PMID- 11764503 TI - [Correction of hepatotoxin effects by lucerne preparations]. AB - The effect of luceron, a phytopreparation from lucerne (Medicago sativa), was studied with respect to the bile secretion and cholopoietic functions and the bile acid spectrum in the blood of rats. It was found that luceron stimulates the bile secretion activity of hepatocytes and normalizes the synthesis of bile acids in rats with model hepatitis. PMID- 11764504 TI - [Various mechanisms of the depriming effect of bacterial endotoxin on drug metabolism]. AB - The effect of an endotoxin from Sh. Boydii on the biotransformation of amidopyrine and acetanilide, the activity of microsomal monooxygenases, hemoxygenase, and xanthine oxidase, the lipid peroxidation (LPO) intensity, the phospholipid spectrum, and the solubilization of microsomal membrane components was studied by intraperitoneal injections (2.5 mg/kg) in rats. It was found that the endotoxin inhibits the reactions of C- and N-acetanilide hydroxylation, N amidopyrine demethylation, acetanilide hydrolysis at the amide bond, conjugation of aminophenol metabolites with glucuronic acid and sulfate, and 4 aminoantipyrine binding to acetate. The endotoxin effect reached maximum 24 h after injection and was observed for 96 h. The inhibition of metabolism of the test preparations is related to a decrease in the content of cytochrome P-450 and in the activity of 1A2, its 2B, 2C, 3A, and 2E1 isoforms. This is obviously caused by activated LPO and enhanced nitric oxide synthesis, as evidenced by a tenfold increase in the content of NO metabolites (nitrites and nitrates) in the blood of test animals. In clinical practice, it is necessary to take into account the possibility of a significant biotransformation of drugs in the acute period of bacterial infection, which may lead to changes in the pharmacological effect and toxicity of some drugs. PMID- 11764505 TI - [Effect of haloperidol on transmembrane potential and viscosity of thymocyte membrane lipids]. AB - A damaging effect of the neuroleptic haloperidol on thymocytes was studied in vivo. The integral state of energetic processes in the cells was described by the electric transmembrane potential of thymocytes delta psi equal to the sum of potential on the plasmic and mitochondrial membranes. The effect of haloperidol was also evaluated by the content of lipid peroxidation (LPO) products and by the structural and functional characteristics of thymocyte membranes (lipid viscosity, protein-lipid interaction). A single administration of haloperidol (0.4 mg/kg) decreased the delta psi of thymocytes and increases the viscosity of lipids in the cell membranes. The content of LPO products--primary (diene conjugates) and secondary (Schiff bases)--was not affected. The obtained results indicate that the combination of methods employed can be used for analysis of the structural and functional characteristics of blood cell membranes (in leukocytes and lymphocytes) for evaluating the side effects of haloperidol in the human organism. PMID- 11764506 TI - [Laxative effect of poly(ethylene oxide) 1500 per se and in combination with bisacodyl]. AB - The results of experiments on rats showed evidence of a laxative activity of poly(ethylene oxide) (PEO-1500) upon peroral administration. This effect is related to the polymer ability of retaining water, which increases the intestinal content volume and accelerates the intestinal peristaltic activity. The anticonstipative effect of PEO-1500 is comparable to that of forlax, but less pronounced than the effect of bisacodyl. The joint administration of PEO-1500 with bisacodyl produces a synergistic effect exceeding the separate action of both agents. PMID- 11764507 TI - [Immunoenzyme test-system for detection of glycyrrhizic acid]. AB - An experimental enzyme immunoassay test kit was developed for detecting glycyrrhizic acid (GA) during pharmacokinetic investigations. This method was used to determine the GA content in the blood plasma of mice and guinea pigs after intraperitoneal and intravenous injections. The results of the GA determination using the new test kit agree with the data obtained by HPLC. PMID- 11764508 TI - [Templates for the automated data processing in spreadsheets in pharmacological studies]. AB - Templates for the automated preliminary data processing and chart plotting immediately during the data setting into spreadsheets are proposed. This technique can be used for better organization of the experimental process involving computer data spreadsheets. Specially developed for Excel, this method can be also used with the spreadsheets of other program packages (Quattro Pro, Lotus, etc.). PMID- 11764509 TI - [Complex evaluation of the effect of bromantane on animal behavior]. AB - The results of experimental investigation of the effect of bromantan on the behavioral activity of rats in the open-field test were treated by a combination of the discriminant and dispersion methods. The toxic effect of the drug on the neurogenic (neurologic) mechanisms conducting the behavior is evaluated. PMID- 11764510 TI - [Pharmacological inhibition of thrombin and plasmin activity]. PMID- 11764511 TI - [Cerebral mechanisms of behavior and higher mental functions]. AB - The paper is dedicated to the 50th anniversary of the Department of Higher Nervous Activity and Psychophysiology at St.-Petersburg State University. PMID- 11764512 TI - [Intersex and interspecies differences in sucrose consumption by rats with various behavioral strategies]. AB - Sucrose consumption by male and female rats during active avoidance acquisition was measured in two rat strains: KLA (Koltushi low avoidance) and KHA (Koltushi high avoidance) selected for divergent performance in a shuttlebox. Under resting condition, there were no interstrain difference in sucrose consumption by males, but KHA females consumed significantly less sucrose than KLA females. Active avoidance acquisition during five consecutive days decreased sucrose consumption in KLA males and did not change sucrose consumption in KHA males. Within a week after exposure to the stress, the sucrose consumption by KLA males returned to its normal values, and KHA males consumed significantly more sucrose. The active avoidance conditioning did not affect sucrose consumption in females of both strains. Substitution of 32% solution for 4% produced on the first day a sharp decrease in sucrose consumption in males of both strains, while females sharply increased consumption of the diluted solution over the next four days of observation. During this time, males returned to consumption of the same volume of the solution despite its decreased concentration. The findings suggest that the exposure to the escapable stress induces the negative affect only in KLA males. PMID- 11764513 TI - [Psychophysiological features of test subjects with different effectiveness of probabilistic-predictive activity]. AB - A correlation between behavioral characteristics of predictive activity and EEG and autonomic indices of the orienting reacting reaction was revealed. A relationship between the personality traits and characteristics of attention, memory, and generalization process was described. PMID- 11764514 TI - [Differences in latent inhibition between men and women under conditions of nonverbal visually-spaatial masking]. AB - In order to study gender differences in development of the latent inhibition (LI) and the influence of laterality (hemisphere) factor, two groups of subjects were examined. In the preexposure phase, subjects of the control group were presented with a pair of geometric figures, which appeared either in the right or in the left visual hemifield (at random) with the exposure time of 80 ms. A subject had to compare the figures in a pair and to press a button in case of their identity. In the preexposure (experimental) group, the subject solved the same task, but half of them was presented with the same set of stimuli which appeared in the right hemifield, another half of subjects received these stimuli in the left hemifield. Simultaneously with the target stimuli, the opposite hemifield was stimulated with a nonattended symbol "[symbol: see text]". In the test phase, all the subjects (both of the control and experimental groups) had to respond to the symbol "[symbol: see text]" (previously nonattended in the experimental group), which appeared in part of the trials, by pressing the button. Pairs of stimuli which had been target ones in the preexposure phase, became masking stimuli in the test phase. Correct responses were reinforced by presentation of a special sound. The number of trials required for acquisition of the instrumental contingency served as an index of the LI. Analysis of variance showed that significant strong effect of the LI was observed only in men (comparison between the control and preexposure groups), while there was no significant difference between women of the control and preexposure groups. There was no laterality effect. Gender differences and hemispheric asymmetry in the LI organization are discussed. PMID- 11764515 TI - [Dynamics of spectral characteristics of theta- and alpha-range EEG during negative emotional reactions]. AB - Power characteristics of the EEG theta and alpha rhythms were studied in a human in neutral state and during a conditioned negative emotional reaction (Fp1, Fp2, F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, and T6 derivations). A significant increase in the relative spectral power in the narrow theta band of 7.4-8.1 Hz in the frontocentral and temporal brain regions was observed during the development of the negative emotional reaction. The alpha-rhythm dynamics during the negative reaction was substantially individual and could be expressed in either an increase, or decrease in relative spectral power of different alpha frequencies. No pronounced changes in their dynamics could also be observed. In some subjects the spectral power of the medium-frequency alpha-rhythm significantly decreased, that of the high-frequency rhythm increased, and changes in the spectral power of the low-frequency alpha range varied. PMID- 11764516 TI - [Intercentral EEG relationships in regressive and chronic post-traumatic Korsakoff syndrome]. AB - Dynamic EEG study of patients with posttraumatic Korsakoff's syndrome (KS) with the application of complex analysis methods revealed a complicated pathological structure of the intercentral relations of cortical electrical activity. The interhemispheric EEG coherence between symmetrical frontal cortical areas are sharply reduced, while the intrahemispheric coherence are increased in comparison with the normal values. The proposed technique of segregation of statistically homogeneous spectro-coherent characteristics made it possible to reveal the earlier intercentral EEG relations formed by stable and variable coherence spectra. The structure formed by the stable and variable coherence spectra in KS differs from that reflected in the mean coherence levels. During the KS regression, the EEG coherence between the right and left frontal areas increased to the normal level, and the variable spectra are revealed. In the chronic KS syndrome, the pathological intercentral relations persist, while the variable relations in the frontal areas are absent. A reduction of pathologically decreased intrahemispheric coherence selectively revealed in the right hemisphere during the KS regression and formation of variable relations in this hemisphere point to a leading role of the right hemisphere in development of compensatory processes in KS. The reciprocal relations between the intra- and interhemispheric coherence and coherence dynamics in the theta rhythm suggest that pathological activity in the basal diencephalic structures plays an important role in formation of the pathological EEG pattern in KS. PMID- 11764517 TI - [Somatosensory evoked potentials during natural and learned patterns of postural adjustment, accompanying limb movements in dogs]. AB - A goal of the study was to investigate cortical reorganization corresponding to inhibition of innate motor patterns during motor learning. Functional changes in the sensorimotor cortex during learned rearrangement of the natural diagonal pattern of postural adjustment (PA) accompanying a hindlimb movement into a new one, the so-called unilateral pattern, were studied in dogs by testing somatosensory evoked potentials (SEP) in response to stimulation of a forelimb during PA immediately before the limb movement onset. During PA the latency and the amplitude of several SEP components decreased. In general, changes in SEP were less pronounced in the learned unilateral pattern of postural adjustment in comparison with the innate diagonal pattern, but the difference was significant only for some SEP components. The SEP late positivity in the learned postural pattern was replaced by a negativity. The SEP changes were similar independently of whether the test stimulus was applied on the forelimb loaded or unloaded during postural adjustment. The data suggest that changes in interrelations between different neuronal populations in the sensorimotor cortex during formation and realization of a learned motor program can be reflected in SEP changes. PMID- 11764518 TI - [Serotonin metabolism in the brain during sexual motivation and activation of the murine hypothalamo-hypophyseal-testicular system]. AB - Serotonin metabolism was studied in male CBA mice during sexual arousal. It was shown that placement of a receptive female into a cage department separated from a male with a perforated partition, which prevented from the physical contact but allowed a male to see and smell a female, caused an elevation of serotonin metabolism. It was originally shown that 10-min female exposure produced in a male an increase in the level of the main serotonin metabolite 5 hydroxyindoleacetic acid (5-HIAA) in the midbrain and its decrease in the hypothalamus. The catabolism coefficient (5-HIAA/serotonin ratio) also increased in the midbrain and decreased in the hypothalamus, while the serotonin content was unchanged. Longer sexual activation of male rats (for 20 min) resulted in an increase in the content of serotonin and 5-HIAA in the amygdala and olfactory bubs, while in the hippocampus only the level of 5-HIAA increased. Thus, for the first time, two stages were distinguished in male sexual arousal. They were determined according to the response of the pituitary-testicular system and involvement of serotonin in different brain regions. PMID- 11764519 TI - [Mechanism of developing "deprivation" potentiation of population responses of neurons in the CA1 field in hippocampal slices]. AB - In rat hippocampal slices, synaptic transmission from Schaffer collaterals to CA1 neurons was studied by assessment of the effects of cessation of low-frequency testing stimulation to the population spike amplitude. A positive correlation between the duration of the stimulation interruption period (from 10 to 120 min) and the increment of the population spike amplitude (from 30 to 100% above baseline level). The "deprivational" potentiation (DP) offers a property of summation and is able to persist for long (testing was continued up to one hour). Prior induction of the long-term posttetanic potentiation (LPTP) that for 1-3 hours prevents the development of the late rather than the short-term LPTP phase, in our experiments also suppressed the DP induction after 60-min stimulation interruption interval. The same results were obtained in the presence of polymixin B (20 mcM), which is an inhibitor of protein kinase C (PKC) and PKC dependent phase of the LPTP. This finding provides support for the earlier assumption about the similarity of the mechanisms responsible for the development of the DP and PKC-dependent LPTP phase related with protein phosphorylation. PMID- 11764520 TI - [Cooperative activity of motor and frontal cortex neurons in trained cats systemically administered M-cholinoreceptor blockers]. AB - It was shown previously that peripherally administered antagonists of the central 1 M-cholinoreceptors led to a selective impairment of bar-pressing response in a food-reinforced operant conditioned task but did not alter contextual behavior and functions such as motivation, perception, and locomotion. To obtain information about the central mechanisms of the conditioning impairment, we recorded simultaneously the extracellular multiunit activity from the frontal and motor neocortical areas of five cats trained to acquisition criteria in a food reinforced operant conditioning task. Multiunit recordings were performed drur 1) normal conditioning; 2) conditioning during subcutaneous administration of muscarinic antagonists scopolamine (0.03 mg/kg), trihexyphenidyl (1 mg/kg), and methylscopolamine (0.03 mg/kg). Autocorrelation analysis showed that scopolamine and trihexyphenidyl but not methylscopolamine led to a significant increase in the tendency of cortical cells to fire in a cyclic way (i.e., the shift of the firing pattern from a single-spike discharge to burst, rhythmic, or rhythmic burst discharge) both in the motor and frontal areas. Cross-correlation analysis showed that the bursting and rhythmic-bursting cells synchronized their activity within and (in a number of cases) between the cortical areas. These changes in the neuronal activity within the motor cortex and frontal cortex were accompanied by a significant decrease in the functional connectivity both inside and between the cortical areas in parallel with selective impairment of the conditioned response. PMID- 11764521 TI - [Features of the stress reaction in rats with genetically-determined emotionality (from EEG indicators)]. AB - The features of the EEG spatial organization in two rat strains, i.e., with expressed emotional reactions (Maudsley reactive, MR) and less reactive (Maudsley nonreactive, MNR) were compared in two stress situations: during exposure to the action of pain (P) (i.p. injection of 0.9% NaCl solution) and during 24-hour water deprivation (D). Multichannel EEG recording (24 derivations) and their multiparametric estimation (840 signs) made it possible to differentiate characteristic features of the EEG spatial organization in rats with initially increased emotional reactions and passive behavioral strategy during exposure to stress. In both stress-inducing conditions, an increase in crosscorrelation and coherence between cortical potentials in parallel with rise of the spectral power in the range of high-frequency theta and its drop in the range of EEG high frequency band was observed in the MR rats. The MNR rats showed the opposite changes. Different reactivity of the ratio between the coherence and spectral power of potentials was observed in two strains of rats. This index characterizes the level of the information-energy component of the spatial organization of cortical potentials. It is suggested that different character of the EEG changes reflects the features of interhemispheric relations, information-energy processes, and cortical regulation of autonomic processes in the system of adaptive stress reactions at different levels of emotionality and behavioral strategy. PMID- 11764522 TI - [Expression of stress-evoked analgesia, connected with activity of animals in a forced swimming test]. AB - The influence of forced swimming on the development of stress-induced analgesia was studied in 35 SHR mice, 65 NMRI mice, and 23 white outbred male rats. Mice were subjected to swimming conditions (at a temperature of 11 degrees C) for a period of 4 minutes and rats for 6 minutes. Pain thresholds were measured by a footshock. It was shown that behavioral response to acute stress is associated with a change in the pain tolerance threshold: activity of an animal under test conditions positively correlated with stress-induced analgesia. The response to stress and parameters of stress-induced analgesia depend on the genetic factor and age, however, the correlation between the activity during exposure to stress and the extent of stress-induced analgesia conserves in all cases. PMID- 11764523 TI - [Shifts in the level of plasma melatonin and changes in circadian locomotion changes after lesioning of the dorsal hippocampus in intact and stressed rats]. AB - Local lesion of the dorsal hippocampus and swimming stress increase the level of plasma melatonin in rats. After hippocampectomy, the disorganization of the circadian locomotion rhythm and inversion of melatonin response to stress were observed. PMID- 11764524 TI - [Effect of immunizing rats with a serotonin-bovine serum albumin conjugate on the structure of diurnal sleep and electrical activity of the brain]. AB - Rats were immunized with bovine serum albumin conjugated with 5-hydroxytriptamine (5-HT). Two injections with a 2-week interval were carried out. At first, rats were injected subcutaneously (2 mg/kg, 0.25 ml) with Freund's adjuvant complete. The second injections (10 mg/kg intraperitoneally) was made 2 weeks later without the adjuvant. One week after the first antigen injection, there were a decrease in the relative power of the electrical activity of the caudate putamen, neocortex, and amygdala in the delta 2 and theta 2 bands and its increase in the alpha and beta-ranges. The number and duration (total and mean) of REM sleep episodes as well as REM sleep contribution in the total sleep duration decreased. These findings testify to a reduced functional activity of the central serotonergic system. Four-five weeks after the first injection, a tendency to a recovery of the bio-electrical spectral pattern and diurnal sleep structure was revealed. Five weeks after the first antigen injection, the titre of antibodies to 5-HT was 1:32-1:64. PMID- 11764525 TI - [Extinction of the defensive conditioned reflex in cats after lesioning the endopeduncularis nucleus]. AB - Influence of bilateral destruction of nucleus entopeduncularis on the extinction of conditioned avoidance was studied in 10 adult cats. It was shown that bilateral destruction of the nucleus entopeduncularis led to a disturbance of storage of the previous conditioning and facilitated repeated extinction. PMID- 11764526 TI - [Size as a parameter for tuning visual attention]. AB - The ability of visual attention to tune to the stimulus size (when this size could not be described by spatial frequencies) was studies. Sinusoidal gratings with frequencies of 1.5, 3, and 6 cycle/degree were used as test stimuli. All these stimuli consisted of 3 periods, consequently, they had different sizes: 2 x 2, 1 x 1, and 0.5 x 0.5 degrees. Three reference stimuli had the same sizes but were constructed as a superposition of all the test frequencies. The reference stimulus of suprathreshold contrast was displayed for 400 ms to the left or to the right of a fixation point at a distance of 3 degrees. After that, the test stimulus of threshold contrast was for 100 ms displayed symmetrically to the fixation point on the other side. Subjects were instructed that the sizes of the reference and test stimuli were the same. It was found that the probability of test detection decreased with increase in the difference between the sizes of the reference and test stimuli. Since in our experiments the spatial frequency could not be used for tuning visual attention, the obtained results suggest that there are specialized mechanisms in the visual system for estimation of the general image size. PMID- 11764527 TI - [Is it possible to train Achatina fulica using visual stimulation?]. AB - The conditioned behavior to visual stimuli was obtained in Achatina fulica mollusk on the basis of its negative phototaxis. Directional moving of snails toward black cards was accompanied by the negative unconditioned stimulation (electric current). Learning was expressed in a statistically significant decrease in locomotor activity of animals and decrease in the rate of preference of sections with black cards. Learning developed within two daily training sessions with 30 trials in each of them. Learning traces were observed as defensive behavior at least during a month after reinforcement elimination. PMID- 11764528 TI - [Detection of moments of operation of functional units in the human cortex using a new method of EEG analysis]. AB - A new approach to EEG processing was proposed. The method allows the poorly predicted points on an EEG recording to be found, which are interpreted as the moments when certain functional units of the brain are engaged or disengaged. The functional units may be probably represented by columns or supercolumns. The method was tested in EEG recordings when the visual illusions were induced in a subject by a rhythmic photostimulation. The method seems to be rather promising. PMID- 11764529 TI - Role of cyclooxygenase inhibitors for the prevention of colorectal cancer. AB - Eicosanoids play an important role in numerous physiologic and pathophysiologic processes in the gastrointestinal tract, including maintenance of mucosal integrity, stimulation of mucus and electrolyte secretion, and inflammation. A rapidly growing body of evidence implicates COX-2 in colorectal carcinogenesis. COX-2 has been shown to alter cellular adhesion, apoptosis, and angiogenesis, contributing to its neoplastic potential. NSAIDs appear to attenuate this potential by mechanisms that are COX-2 dependent and independent. Several advances have been made in understanding the details of COX-2 regulation. The downstream effect of COX-2-dependent metabolites varies with the enzymatic machinery present in a particular cell, the level of COX activity, differences in location and types of prostaglandin receptors, and differences in signal transduction pathways. Further studies are needed to understand better these complex interactions, which may provide insight into the role of COX-2 in pathologic conditions, such as intestinal inflammation and colorectal cancer. PMID- 11764530 TI - COX-2 inhibitors. Are they nonsteroidal anti-inflammatory drugs with a better safety profile? AB - In the treatment of arthritis, NSAIDs are some of the most commonly used drugs, although the prescription of such drugs has been questioned due to their inherent risks for gastrointestinal compromise, platelet effects, and the potential for renal toxicity with long-term use. With the availability of celecoxib and rofecoxib, 2 cyclooxygenase (COX-2) inhibitors (or COX-1 sparing agents) as new forms of NSAIDs, these issues have become magnified not only in the context of risk-to-benefit ratios but also interms of pharmacoeconomics because they have been proven to be equally efficacious as the nonselective NSAIDs, with an improved safety profile particularly within the gastrointestinal tract, but at a significantly increased cost. PMID- 11764531 TI - An evidence-based approach to the gastrointestinal safety profile of COX-2 selective anti-inflammatories. AB - Evidence-based medicine (EBM) provides frameworks for the systematic review of study methodology and results. Thus, EBM frameworks facilitate assessing a study's ability to produce unbiased and accurate results and applying the results to the management of individual patients. Using EBM frameworks, published literature about risk factors for serious NSAID-associated gastrointestinal (GI) disorders, GI safety of COX-2 selective NSAIDs, and GI safety of co-therapy of proton pump inhibitors and NSAIDs are reviewed. This article concludes with evidence-based recommendations concerning which patients are at high risk for serious NSAID-associated GI disorders and which therapies are most effective in reducing serious NSAID-associated GI disorders. PMID- 11764532 TI - Prostaglandin biology. AB - PGs are important mediators of normal physiology, response to injury, and pathologic processes. Dissecting these biochemical and molecular pathways allows development of therapeutic agents that can be [figure: see text] applied to specific clinical situations, while preserving PGs that play a role in normal physiology. PMID- 11764533 TI - Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. AB - When considering the diseases of the stomach and duodenum, peptic ulcer disease has been the one of greatest clinical impact. Although there are several components that contribute mechanistically to ulcer disease, it is recognized that gastroduodenal mucosal prostaglandins play a central pathogenic role, especially in ulcers related to the use of NSAIDs. As a result of understanding the mechanisms of NSAID-induced ulceration, the crucial function that gastroduodenal mucosal prostaglandins have in mucosal defense and repair is appreciated. It now is held widely that mucosal prostaglandin deficiency increases susceptibility to ulcer formation and that exogenous administration of supplemental prostaglandins reduces ulcer risk. This article reviews the role that mucosal prostaglandins play in defense of the gastric and duodenal mucosa against injury and ulceration. PMID- 11764534 TI - Gastrointestinal toxicity associated with nonsteroidal anti-inflammatory drugs. Epidemiologic and economic issues. AB - The large body of literature on the gastrointestinal side effects of NSAIDs has shown consistently that populations can be identified that have a markedly elevated risk for these iatrogenic conditions. These groups include the elderly, persons with prior history of peptic ulcer disease and its complications, persons receiving anticoagulant and corticosteroid therapy, and persons who require long term NSAID therapy, especially at high dose. It is possible that several comorbidities (e.g., rheumatoid arthritis) predispose patients to gastrointestinal complications caused by NSAIDs, but few studies have adjusted carefully for the possibility that concomitant medication use (e.g., oral anticoagulants, corticosteroids) or increased NSAID dose may account best for apparent association of comorbidities as a risk factor for serious gastrointestinal events. The role of H. pylori infection in affecting the risk of complicated ulcer disease among NSAID users remains to be fully elucidated. Low dose aspirin for cardioprotective use is associated with an increased risk for PUBs; when used concomitantly with NSAIDs, this increases the risk of PUBs above that of the NSAID itself. Apart from the physical toll NSAID-related gastrotoxicity places on the patient, there are considerable economic consequences to patients, providers, and society. This cost presents a subject for research for those interested not only in improving the quality of patient care, but also in the prudent use of health care resources. PMID- 11764535 TI - Gastrointestinal safety of COX-2 specific inhibitors. AB - Coxibs are a major advance in the therapy of patients with painful and inflammatory conditions. At present, the theoretical harm that derives from inhibiting vascular COX-2 has not emerged as a significant risk, although more research is needed. What has emerged is that some NSAIDs, particularly naproxen, may have an aspirin-like effect in reducing the risk of vascular disease, although more research is needed. Whether this finding is sufficient to recommend naproxen for the management of patients with arthritis who also require vascular protection is intriguing and worth further evaluation. It is widely believed and maintained that coxibs have the greatest potential value in patients with other risk factors for ulcer disease, and this seems likely to be the case for patients taking corticosteroids or anticoagulants and probably those who are elderly. Dosing should be [figure: see text] cautious in old patients, however, because of the ability of NSAIDs and coxibs to cause fluid retention, heart failure, and hypertension. It is less clear that coxibs reduce risk sufficiently in patients with previous ulceration (particularly recent) to make them a better strategy than acid co-therapy. This possibility requires further evaluation, as does the competing value of the 2 strategies for patients infected with H. pylori. If coxibs are used in patients with H. pylori-associated risks, there are grounds to recommend eradication. For patients taking aspirin or drugs [figure: see text] with an aspirin-like effect, the intrinsic risk of these drugs may mandate use of acid suppression and obviate the use of coxibs (Fig. 8). Available data suggest that the risk reduction in patients with no risk factors who use coxibs may be almost as great as in patients with risk factors, with the added advantage that patients may be taken to a state that is virtually free of any risk of ulcer complications that otherwise might require additional therapy. Contrary to current popular truisms, the greatest value of coxibs may be in patients without risk factors because it is in this unconfounded group that the ability of coxibs to free patients of ulcer risk appears to be delivered in full. PMID- 11764536 TI - Helicobacter pylori and nonsteroidal anti-inflammatory drugs. AB - The complex interaction between H. pylori and NSAIDs implies that it is over simplistic to conclude that their relationship is independent, synergistic, or antagonistic without considering the influence of other factors. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs and low-dose aspirin all affect the outcome. Several recommendations can be made with regard to the indications of H. pylori eradication for patients requiring NSAIDs. First, patients taking NSAIDs who have ulcers or previous ulcer disease should be tested for the bacterium, and it should be eradicated if present because it is impossible to determine whether the ulcers are caused by H. pylori or NSAIDs or both. Antiulcer drugs should be prescribed to prevent ulcer recurrence for patients who continue to require NSAIDs. Although the efficacy of omeprazole is enhanced by H. pylori infection, it is not justified to leave a pathogen in the stomach in exchange for a modest therapeutic gain. Second, for patients who take low-dose aspirin, eradication of H. pylori substantially reduces the risk of ulcer bleeding. It is advisable that patients taking low-dose aspirin who are at risk of ulcer bleeding should be tested for H. pylori and treated for it if the infection is found. Third, for patients who are about to start NSAIDs, screen-and treat H. pylori has the potential of reducing the ulcer risk at an affordable incremental cost. It might be argued that any interaction between H. pylori and NSAIDs would become irrelevant in the era of COX-2-selective NSAIDs. Even among patients who are receiving a COX-2-selective NSAID, however, a large-scale study showed that the ulcer risk is significantly higher in H. pylori-positive patients than in uninfected patients. This finding suggests that the relative importance of H. pylori in ulcer development might increase with a reduced toxicity of COX-2 selective NSAIDs. With an increasing use of low-dose aspirin for cardiovascular prophylaxis, the problem of aspirin-related ulcer disease is expected to rise. Given the significant role of H. pylori in the latter condition, screen-and-treat H. pylori might be a useful strategy for the prevention of ulcer complications in high-risk patients receiving low-dose aspirin in the future. PMID- 11764537 TI - Clinical implications of prostaglandin inhibition in the small bowel. AB - NSAID-induced intestinal toxicity is more common than previously recognized and may have clinically significant sequelae, especially in elderly arthritic patients. Increased awareness of the potential intestinal complications associated with prostaglandin inhibition is required for early recognition and appropriate management. An increase in the level of suspicion by physicians may lead to earlier diagnosis and subsequent discontinuation of the offending NSAID; this is important in that discontinuation of the offending agent may be preferable to multiple endoscopic radiologic and surgical procedures in the patient with obscure blood loss and anemia. Appropriate diagnosis in selected patients may prevent the increased morbidity and mortality associated with small intestinal surgery. The emergence of selective COX-2 inhibitors likely will bring this issue to the forefront because it will become increasingly important to determine the effects of these agents on the small intestine and colon, in addition to their effects on the gastroduodenal mucosa. The new generation of selective COX-2 inhibitors may offer a potential therapeutic advantage over the nonselective NSAIDs with respect to their intestinal toxicity. Well-designed safety trials that have intestinal injury as a predefined end point will provide important information as to the overall gastrointestinal safety of these compounds. These agents must be evaluated with respect to their overall safety profile and not just by their gastrointestinal safety. Nevertheless, these agents are continuing to provide new directions for exciting basic and clinical scientific investigation. PMID- 11764538 TI - Prostaglandin biology in inflammatory bowel disease. AB - Similar to in the upper gastrointestinal tract, prostaglandins represent one of the most important components of mucosal defense in the small intestine and colon. The effects of prostaglandins in this context are widespread, ranging from maintenance of blood flow to stimulation of mucus secretion to modulation of the mucosal immune system. There is little doubt that the ability of NSAIDs to cause injury throughout the gastrointestinal tract and to exacerbate IBD is due in large part to the ability of these agents to suppress prostaglandin synthesis. With the advent of selective COX-2 inhibitors, it has become possible to dissect further the roles of prostaglandins in mucosal defense. The weight of evidence collected so far suggests that prostaglandins derived from COX-2 are important in promoting the healing of mucosal injury, in protecting against bacterial invasion, and in down-regulating the mucosal immune system. Suppression of COX-2 in a setting of gastrointestinal inflammation and ulceration has been shown in experimental models to result in impairment of healing and exacerbation of inflammation-mediated injury. In the near future, pharmacologic probes will be available that will permit clinicians to identify better the specific prostaglandin receptors that mediate the effects of this group of mediators on the various aspects of mucosal defense. This identification should permit the development of therapeutic agents that specifically can modulate some aspects of mucosal defense without having undesired effects on other aspects of mucosal function. Such agents may permit clinicians to enhance mucosal repair selectively and to block selectively any contribution of prostaglandins to the pain associated with IBD. PMID- 11764539 TI - Prostaglandin inhibitors and the chemoprevention of noncolonic malignancy. AB - Much has been learned about the role of NSAIDs as cancer preventives through epidemiologic and experimental studies. The pathways of carcinogenesis in the gastrointestinal tract are initiated by many different genetic, environmental, infective, and lifestyle factors. It is possible that the final common pathway of all these malignancies may have some common features. It is conceivable that head and neck, esophageal, gastric, and colorectal epithelial carcinogenesis all are influenced by or require COX-2 up-regulation as a step toward transformation. Intuitively, it is possible that selective COX-2 inhibitors may have a preventive role in all these epithelial malignancies. Today's challenge is to translate this information into clinical trials to define what role, if any, COX inhibition might play in the prevention of these malignancies. PMID- 11764540 TI - [Androgen treatment of erectile problems]. PMID- 11764541 TI - [Renal conservative surgery with selective renal parenchymal clamping]. PMID- 11764542 TI - [Treatment of undescended testis: after what kind of evaluation? why? when? how?]. PMID- 11764543 TI - [Incidental disclosure of juxta-hilar mass in the left kidney]. PMID- 11764544 TI - [Diagnosis of prostatic cancer: how far to go?]. PMID- 11764545 TI - [Treatment of enuresis in children]. PMID- 11764546 TI - Programmable shunt radiography. AB - This article discusses a programmable ventricular shunt valve system used to treat hydrocephalus. With this system, valve pressure can be ascertained easily with plain-film radiographs, thus avoiding complications associated with inappropriate pressures. The authors describe the shunt's design and techniques for imaging it, present illustrative cases and outline a strategy for coordinating the care of patients with these shunts. PMID- 11764547 TI - Deterrents to R.T. continuing education. AB - Constant changes in medicine and technology make continuing education (CE) vitally important for radiologic technologists. Understanding what deters radiographers from participating in CE may help improve CE programs. This article reports on a survey of deterrents to CE participation among radiographers. Results revealed that cost was the leading deterrent, followed closely by work constraints. In addition, certificate-level radiographers found lack of quality to be a significantly higher deterrent than did radiographers with an associate degree. PMID- 11764548 TI - Coronary artery disease and electron-beam CT. AB - Because its precision allows early detection of atherosclerotic processes in patients exhibiting no or few symptoms, electron-beam computed tomography (EBCT) will play an increasingly important role in the assessment of coronary artery disease (CAD). This article provides an introduction to CAD, traditional imaging approaches for its assessment, and the rationale and methods used in CAD-related EBCT imaging. The article also discusses the promise and limitations of using EBCT to detect, assess and monitor CAD, particularly in asymptomatic patients. PMID- 11764549 TI - Radiologic aspects of street drug abuse. AB - The use of illicit substances is a worldwide problem. In the United States alone, governmental agencies spend more than $30 billion per year combatting drug abuse. While the war on drugs affects every citizen in one way or another, radiologic technologists have become active participants in the effort. This article offers an overview of common street drugs and discusses the role of medical imaging in diagnosing drug-related injuries and chronic conditions, studying the physiology of addiction and aiding law enforcement. PMID- 11764550 TI - A new generation on the horizon. PMID- 11764551 TI - A database of radiologic technologists. PMID- 11764552 TI - The challenge of outcomes assessment. AB - While many programs undertake formal assessment of student learning outcomes to satisfy accreditation standards, the ultimate goal of outcomes assessment is program improvement and increased student achievement. Properly designed and executed, outcomes assessment should tell the program how well it is operating and the extent to which it is contributing to the growth and development of its students. It enables programs to determine if they are effective in producing graduates with the necessary knowledge, skills and values to function as valuable members of the health care team, thus contributing to improved quality of patient care. PMID- 11764553 TI - Radiographic markers: friend or fomite? PMID- 11764554 TI - The heart of the matter. PMID- 11764555 TI - Promoting autonomy in elderly patients. PMID- 11764556 TI - R.T.s must make their needs a priority. PMID- 11764557 TI - Vaccines and biologicals. Part I. PMID- 11764558 TI - [Required quality levels of underground drinking water concerning the presence of arsenic]. PMID- 11764559 TI - [Helsinki Declaration VI: a necessary revision, but sufficient?]. AB - With the fifth amendment of the Declaration of Helsinki (Edinburg, 2000), the World Medical Association took a fundamental step forward in the history of the document, after years of internal and external debate. The Declaration was firstly adopted in 1964 as a clear intent to show that the medical profession could manage the ethical control of medical research with human beings. However, several disgraced episodes, like the Tuskegee Syphilis study, showed the insufficiency of such a system. An external control in the form of legal regulation was then proposed. Paradoxically, the importance of the Declaration did not decrease because many national regulations included it as a reference, actually providing it a legal status. But, though formally important, the Declaration hardly had an impact on real-world terms, because it assumed an old fashion logic of clinical research failing to incorporate the modern methodological developments. The amendment could not be put off longer. In the present paper, I analyse the main shortcomings of the Declaration before the 2000 amendment and to what extent the fifth revision has corrected them. PMID- 11764560 TI - [Arsenic levels in drinking water supplies from underground sources in the community of Madrid]. AB - BACKGROUND: In 1998, arsenic concentrations of more than 50 micrograms/l were detected in some drinking water supplies from underground sources in the Autonomous Community of Madrid, which is the maximum permissible concentration for drinking water in Spain. These two facts have meant the getting under way of a specific plan for monitoring arsenic in the drinking water in the Autonomous Community of Madrid. METHODS: The results of the first two sampling processes conducted in the arsenic level monitoring plan set out are presented. In the initial phase, water samples from 353 water supplies comprised within the census of the Public Health Administration of the Autonomous Community of Madrid were analyzed. A water supply risk classification was made based on these initial results. In a second phase, six months later, the analyses were repeated on those 35 water supplies which were considered to possibly pose a risk to public health. RESULTS: Seventy-four percent (74%) of the water supplies studied in the initial phase were revealed to have an arsenic concentration of less than 10 micrograms/l, 22.6% containing levels of 10 micrograms/l-50 micrograms/l, and 3.7% over 50 micrograms/l. Most of the water supplies showing arsenic levels of more than 10 micrograms/l are located in the same geographical area. In the second sampling process (six months later), the 35 water supplies classified as posing a risk were included. Twenty-six (26) of these supplies were revealed to have the same arsenic level ((10-50 micrograms/l), and nine changed category, six of which had less than 10 micrograms/l and three more than 50 micrograms/l. CONCLUSIONS: In the Autonomous Community of Madrid, less than 2% of the population drinks water coming from supplies which are from underground sources. The regular water quality monitoring conducted by the Public Health Administration has led to detecting the presence of more than 50 micrograms/l of arsenic in sixteen drinking water supplies from underground sources, which is the maximum permissible level under the laws currently in force in Spain. Measures have been taken to prevent water from being used from these water supplies. Around 20% of the water supplies studies must take measures in the near future to lower the arsenic concentration to below 10 micrograms/l when the water directive which is currently in the process of being written into Spanish law enters into effect. PMID- 11764561 TI - [Changes in mortality caused by accidents in children and their geographic distribution in Spain (1975-1994]. AB - BACKGROUND: In the developed countries, child accidents are ranked as one of the leading causes of death. The purpose of this study is to describe the 1975-1994 trend in Spain and its breakdown by Autonomous Communities. METHODS: The following indicators have been calculated based on the official death statistics accidental deaths and populations in Spain and their Autonomous Communities for the 1-14 age range: percentages of total deaths, gross death rates, age-related rates, specific rates by age groups and related risks broken down by figures for the females and males, year of death and Autonomous Community. RESULTS: During the 1975-1994 period, accidental child death rates in Spain have fallen by 3% annually for females and by 3.5% for males. The male/female ratio remained at approximately two (2). Traffic accidents totaled around 50%. Aragon showed the lowest relative risk for females (0.54) as well as for males (0.57), Galicia having shown the highest (1.73 for females, 1.91 for males). The percentage of the total number of child deaths varied greatly from one Autonomous Community to another, while the percentage of traffic accidents was around 50% in all of the Autonomous Communities. CONCLUSIONS: In Spain, the child accidental death rate has dropped remarkably, it being estimated that currently 50% less die than in 1975. The breakdown by Autonomous Communities revealed certain major differences. PMID- 11764562 TI - [Evaluation of health surveillance at several primary care units in Cuba]. AB - BACKGROUND: The organization and operation of the epidemiological monitoring carried out at several Primary Care facilities in Cuba was assessed by means of a study conducted for the purpose of ascertaining the effectiveness of the monitoring in question and of contributing to further improve the mechanisms thereof and thus improve the health conditions of the population. This assessment was implemented at eight Polyclinics in the city of Havana throughout the 1998 1999 period. METHOD: By means of the implementation of an integral methodology, an assessment was made of the three factors involved in the monitoring system at the facilities in question, that is, the organization, the process and the results thereof. For this purpose, a survey which quantified some aspects of the system (sensitivity, opportunity, representativeness, usefulness) and a semi structured survey of epidemiologists and other physicians involved in the monitoring in question in addition to the users of the system was used. RESULTS: The assessment of the organization revealed the monitoring organization to be adequate. In the assessment of the process, sensitivity was found to be low at some polyclinics, problems existing at many of them with regard to the opportunity and flexibility of the system. The assessment of the results of the monitoring revealed them to be satisfactory as regards their effectiveness for detecting acute events, as well as in the perception of the users with regard to the usefulness of these results for solving the problems pinpointed. CONCLUSIONS: The monitoring done at the polyclinics assessed is indicative of there being an adequate organization of the monitoring, although some shortcomings were found to exist with regard to the fulfillment of some aspects of the monitoring. This however has no bearing on the results for the system as a whole, which is capable of detecting any epidemiological situation of importance and of suggesting appropriate measures for controlling the situation. PMID- 11764563 TI - [Comparative study of Salmonella and Campylobacter infections in Huesca. 1996 1999]. AB - BACKGROUND: The Salmonella and Campylobacter genera are the main bacterial agents causing enteritis in humans in the developed countries. The purpose of this paper is to study the descriptive characteristics of the cases of infection by Salmonella and by Campylobacter and to describe their trend and seasonal variance in the province of Huesca for the 1996-1999 period. METHOD: The sources of information were the Hospital Microbiological Laboratories (HML's) which conduct coproculture analyses of both outpatients and inpatients. The municipality is taken as the reference unit for plotting the space distribution. For the study of the trend, a multiplicative determinist model is used for grouping the data into four-week periods. RESULTS: A total of 781 cases of infection by Salmonella and 654 cases of infection by Campylobacter have been included, respectively showing mean annual rates of 95 and 79.5 x 10(5) inhabitants. The enteritis by Campylobacter occurs mainly in children under five years of age (73.4%), as compared to the 35.5% of the cases of salmonellosis. The situation is the reverse in the case of the hospital admission percentages, hospitalization due to salmonellosis hence being nearly five times greater. Both of these genera are of a clear-cut seasonal nature, showing a marked peak in the month of August. CONCLUSIONS: A growing trend in the number of positive isolations for both of these organisms and a clear seasonality in the summertime have been found. PMID- 11764564 TI - [Outbreak of Trichinella britovi infection in Granada in the spring of 2000]. AB - BACKGROUND: The magnitude of the epidemic depends upon the scope of the contaminated product distributed. In the spring of 2000, an episode caused by the sale of sausage products which had not undergone health inspection. The purpose of this study is to provide an epidemiological description of the outbreak caused by Trichinella britovi. METHODS: Descriptive study of the control measures and those affected. The food products contaminated with this parasite was investigated by means of an epidemiological survey. RESULTS: Thirty-eight (38) cases were reported throughout weeks 18-22 of the epidemic. The symptoms most often reported were fever, myalgia and palpebral edema. Eighty-seven percent (87%) of those affected tested positive for eosinophilia. Forty percent (40%) required hospitalization. Late diagnosis was curtailed once the alert had been broadcast. T. Britovi was found in the sausage product. CONCLUSIONS: Trichinellosis epidemics can occur despite the current inspection and control systems, placing food safety at risk. Broadcasting a health alert curtails late diagnosis. We propose intensifying health education and continuing the implementation of duly supervised and evaluated self-check programs in industries and establishments. A well-tuned, fast-reacting epidemiological monitoring system must be kept in place. PMID- 11764565 TI - [Some aspects of microsurgical decompression of neurovascular formations of the spinal canal in lumbar osteochondrosis]. AB - Microsurgical techniques have been developed for decompression of neurovascular formations of the vertebral canal in lumbar osteochondrosis. Surgical policy has been proposed in relation to the site of hernial prolapse by the disk diameter. The use of this policy provides the minimal traumatism of surgical interventions in posterolateral hernias in particular. PMID- 11764566 TI - [Features of the clinical course of intravertebral disk herniation in degenerative lumbar stenosis]. AB - The paper presents a clinical and neurological analysis of 110 patients with discal hernias who were divided into 2 groups: 1) 50 patients with normal sizes of the vertebral column; 2) 51 patients with its stenosis. Compression syndromes were major in all cases. In patients in whom discal hernia was concurrent with lumbar stenosis, the clinical course was characterized by dull or aching pains in the low back and legs, by symptoms of dysbasia neurasthenica intermittens, severe motor and sensory disorders with autonomic impositions. PMID- 11764567 TI - [A gigantic adamantinoma of the base of the skull, projecting into the chiasmosellar region, clivus, sphenoidal, cribate, and maxillary sinuses, and nasopharynx (a case)]. PMID- 11764568 TI - [Successful use of a cell saver in massive blood loss in pediatric neurosurgery (a case)]. PMID- 11764569 TI - [Features of cranio-cerebral trauma in victims of road accidents]. AB - The paper deals with the specific features of brain injury (BI) in victims of road traffic accidents (RTA). RTA victims are most commonly pedestrians (62.6%) and less commonly drivers (17.5%). In over half the cases (62.6%), BI due to RTA is associated with extracranial lesions, leading to diagnostic problems. The pattern and site of lesions are related to the type of a transport vehicle and to the role of a victim as a traffic participant. Multiple extracranial lesions are mostly frequently encountered in victim pedestrians (30.3%), BI concurrent with chest damage is common in drivers (12.8%), BI concurrent with "whip" injury of the cervical spine is found in drivers and passengers though such combinations may also seen in pedestrians (1.5%--5 cases). The most severe form of brain compression is multifactorial compression (27.6%) and its most common form is compression with subdural hematoma (35.3%). PMID- 11764570 TI - [Compression of the inferior cerebellar artery-induced compression of the medulla oblongata in Arnold-Chiari malformation as a cause of essential hypertension]. AB - Cerebrovascular abnormalities (primarily looping of cerebellar arteries) are almost without exception concurrent with the Arnold-Chiari syndrome and hydrocephalus. Persistent essential hypertension may be a manifestation of pathological vessel-brain contact. Customary microvascular decompression may lead to blood pressure stabilization in the postoperative period for a long time. The paper presents a clinical case of a 52-year female patient with the Arnold-Chiari syndrome who underwent microvascular decompression of the left posterior inferior cerebellar artery at the level of the medulla oblongata. Surgical treatment regressed preoperative cerebellar, bulbar, and truncal symptoms, lowered blood pressure from 190/100 to 120/80 mm Hg, and stabilized it at this level. PMID- 11764571 TI - [Calculation of targets of destruction by magnetic resonance tomography during stereotactic anterior callesotomy]. PMID- 11764572 TI - [Retrosigmoid suboccipital access]. AB - Retrosigmoid suboccipital access has been widely used in neurosurgical care for more than a century. It has been employed in different vascular diseases and tumors of the brain. The authors provide examples of how to use the retrosigmoid suboccipital access, a patient's position during its application and techniques. All stages of performance of the access, including trepanation of the internal acoustic meatus, are considered in detail. Emphasis is laid in the advantages and disadvantages of this access. The basic stages of the access are illustrated. Correct application of the retrosigmoid suboccipital access is stated to yield a good view of primarily the cerebellopontile angle and causes no its associated complications. PMID- 11764573 TI - [Immunologic aspects of embryonal nerve tissue transplantation]. PMID- 11764574 TI - [International symposium "Basal Ganglia and Thalamus in Health and in Motor Disorders (Moscow, 29-31.05.2000)]. PMID- 11764575 TI - [Microsurgical treatment of multi-level diskogenic damage of the lumbar region of the spine]. AB - The paper deals with microsurgical treatment of multi-levelled lumbar discogenic lesions. Fundamental interventional principles including preservation of the supportive ability of vertebromotor segments, reparative surgical techniques, and intraoperative procedures for prevention of scarring and adhesive processes are shown. Criteria for choosing the scope of an intervention in multi-levelled lumbar discogenic pathology are presented. The surgical policy proposed ensures the maximal decompression of neural and vascular structures of the vertebral canal, improves the outcomes of treatment, and reduces the number of reoperations. PMID- 11764576 TI - [Rheolytic thrombectomy using the "Angiojet" complex in treating arterial thrombosis]. AB - Results of roentgenendovascular treatment of arterial thrombosis by rheolytic thrombectomy with "Angiojet" are presented. 18 patients (1 woman, 17 men) underwent 19 rheolytic thrombectomies from peripheral arteries. Mean age of patients was 53.3 +/- 3.0 years, time of thrombosis--from 20-30 min to 60 days (mean 121 +/- 17 hours). Thrombectomy was performed from superficial femoral, popliteal or tibial arteries, or from all these vessels simultaneously. In one case thrombus was removed from femoro-popliteal graft. Rheolytic thrombectomy was combined with balloon angioplasty of hemodynamicaly important stenosis, 5 patients underwent implantation of 9 stents. Good and satisfactory results were achieved in 77.8% patients; thrombectomy as the stage of operation was ineffective in one case only. Rheolytic thrombectomy from coronary arteries was performed 3 times, with complete effect in 1 and with partial--also in 1 patient. PMID- 11764577 TI - [Repair of nerve defects with autotransplants]. AB - Over 15 years (1985-1999) 60 plastic reconstructions of nerve defects with autograft were performed after peripheral nerves injuries of the upper limbs (42 patients), lower limbs (14) and face (4). It is demonstrated that efficacy of surgery depends on period from injury to surgery, age of patient, length of autograft, nature and location of injury, kind of injured nerve. Better results were achieved after operations on peripheral nerves of the upper limbs. After operations on lower limbs more favorable results were achieved in repair of tibial nerve defects. Plastic surgery of facial nerve defects gave satisfactory results. Time from injury to surgery is the main factor essential for surgery result. PMID- 11764578 TI - [Surgical tactics in benign nodal lesions of the thyroid]. AB - Results of surgical treatment of 2307 patients with different forms of thyroid nodal diseases over 11 years (1989-2000) were analyzed. It is necessary to perform organ-saving operations to reduce postoperative complications rate and save hormone-producing function of the thyroid gland: after thyroid resection the rate of postoperative hypothyrosis was 7.9%, after hemithyreoidectomy and subtotal resection--92.4%. Recurrence was revealed in 10.7% cases in 3.7 years, on the average, that testifies to radical surgery. Resection with removal of node in limits of intact tissue was performed according to the results of morphologic examination of both node and surrounding thyroid tissue: discirculation with fibrosis were seen in 69.7%, dystrophic processes with secondary thyroiditis--in 24.3% cases. Etiology and morphology of the node are the main factors of pathogenesis of recurrence. Organ-saving operations and consideration of endocrinological aspects permitted to cure radically 89.3% patients. PMID- 11764579 TI - [Cytologic characteristics of bronchitis in patients with acute lung abscesses]. AB - Results of cytological examination of smears obtained after brush-biopsy from mucosa of ostium of bronchus which drains cavity of acute abscess were analyzed in 96 patients. Correlation between number of neutrophils, eosinophils, monocytes and fibroblasts was demonstrated. Criteria of inflammation intensity evaluation in endobronchitis were developed. It is necessary to combine endoscopic examination with cytological examination of smear. PMID- 11764580 TI - [Diagnosis and treatment of diffuse esophagospasm]. AB - 123 patients with diffuse esophagospasm were observed, including 56 (45.5%) with primary and 67 (55.5%) with secondary esophagospasm. Since 1986 due to unsatisfactory treatment results an original therapeutic complex including spasmolytics, neuroleptics, vitamins B, was used. In secondary esophagospasm therapy was complemented by pneumocardiodilatation, not more 5 sessions per course. Good and satisfactory clinical results were achieved in 30 (66.7%) patients with primary diffuse esophagospasm and in 45 (67.2%) patients with secondary esophagospasm. PMID- 11764581 TI - [Gastrectomy in treating gastric hemorrhage]. AB - Use of gastrectomy for gastric bleeding in emergency cases is analyzed. Gastrectomy was performed in 15 patients over 7 years. When tumor of the stomach penetrated into other organs combined operations were performed: gastrectomy with splenectomy and left-sided hemipancreatectomy, gastrectomy with cholecystectomy, choledocholythotomy and choledochoduodenostomy. Results of treatment were good. There were no lethal outcomes. New variant of gastrectomy was developed and performed in 5 patients. Technical simplicity and reliability of esophagoduodenal anastomosis, optimal functional result and good life quality were demonstrated in gastrectomized patients. PMID- 11764582 TI - [Diagnosis and treatment of pancreatic peritonitis]. AB - Results of diagnosis and treatment of 71 patients with general pancreatogenic peritonitis (7.3% of all patients with general peritonitis) are analyzed. The main diagnostic methods were ultrasound (100% cases), computed tomography (29.5%), laparoscopy (60%). Based on clinical, instrumental, bacteriologic and morphologic examinations primary and secondary pancreatogenic peritonitis are distinguished. Optimal policy of treatment depended on peritonitis forms. In primary (enzyme peritonitis) minimally invasive methods of treatment were used: laparoscopic drainage of abdominal cavity and bursa omentalis, therapeutic blockades etc. in secondary (bacterial) peritonitis wide laparotomy with sanations of abdominal cavity and minor bursa omentalis were used. Consecutive necrectomies and sequestrectomies were preferred (70.2%). Advantages of hemofiltration over other methods of efferent therapy are demonstrated. The above methods of treatment permitted to decrease postoperative lethality in secondary purulent pancreatogenic peritonitis from 68 to 44%. PMID- 11764583 TI - [Prospects for surgical and combined methods for treating acute coronary syndrome]. AB - From 1997 to 2000 diagnostic coronaroangiography was performed in 334 patients with acute coronary syndrome (ACS) which is the group of diseases with common pathophysiological mechanism, namely coronary artery thrombosis. ACS needs revascularization of the affected artery as quickly as possible. 26.6% patients underwent balloon angioplasty (BAP). 14.9% patients underwent emergency and urgent coronary artery bypasses with cold and pharmacological cardioplegia. Minimally invasive coronary bypass (MICB) was used in 4.2% patients. Combined BAP + MICB were performed in 2.1% patients. Indications, terms, sequence and future of ACS surgical treatment are discussed. PMID- 11764584 TI - [Intraabdominal cholerrhea after cholecystectomy]. AB - Cholecystectomy (CE) was performed in 2303 patients with cholelithiasis and its complications. Cholerrhea (CR) after operation was in 31 (1.34%) patients: after laparoscopic CE (1425 patients)--in 18 (1.26%), after open CE (878 patients)--in 13 (1.48%). Source of CR was not found in 21 patients, CR from gall bladder bed was revealed in 7, from cystic duct stump--in 2, from hepaticojejunoanastomosis- in 1 patient. Ultrasonic examination, endoscopic retrograde pancreatocholangiography, laparoscopy were used for diagnosis of this complication. CR stopped spontaneously in 19, after endoscopic papillosphincterotomy--in 4 patients. Spread of bile in abdominal cavity was revealed in 6 patients, 4 of them underwent laparoscopic operations, 2--open operations. Infrahepatic encapsulated bile clumps were in 2 patients, they underwent ultrasonic-assisted drainage. PMID- 11764585 TI - [Bouginage in chemical burns of the esophagus in children]. AB - 851 children suspected to have chemical burn of the esophagus were treated from 1996 to 2000. Use of esophageal bouginage along the guiding string has changed medical policy for esophageal burns. We completely rejected early bouginage. Late bouginage was necessary for 22% patients with II-III degree of chemical burns (3.8% of all hospitalized children). Results of the new policy depended on chemical agent. The best results were achieved after acetic acid burns. It is difficult to treat alkali burns leading to prolonged esophageal stenosis, and manganese crystal burns leading to pharynx injuries. PMID- 11764586 TI - [Analysis of long-term results of surgical treatment of anorectal maldevelopment in girls]. AB - 77 girls with anorectal maldevelopments were treated from 1979 to 1999. Long-term results were followed up from 2 to 20 years in 65 patients. Functional methods of sphincters examination, clinical examination and interview were used. Good and satisfactory results were achieved in 90% patients. Complex of functional methods, clinical examination and interview permits to evaluate objectively long term results of anorectal maldevelopments' surgical treatment. The modification of Riccioli operation has a number of advantages over other surgical methods of treatment of anorectal maldevelopments with fistulas into genital organs and permits to achieve good long-term functional results in the majority of patients with intermediate and lower forms of anorectal maldevelopments. PMID- 11764587 TI - [Predicting purulent complications in surgery by determining antibody affinity]. AB - Blood serum of 153 operated patients was studied, 133 of them had uncomplicated postoperative period, 20 patients had postoperative infectious complications. Control group consisted of 23 healthy donors. Coefficient of antibodies affinity was deduced mathematically. If this coefficient didn't exceed 15%, probability of complications development was 90%; if this coefficient ranged from 15 to 30%, probability of complications was 50%; if coefficient exceeded 30%, complications in postoperative period were the least probable. This method can be used for humoral immunity evaluation in surgical patients, bearing in mind its prognostic and diagnostic significance. PMID- 11764588 TI - [Videothorascopic monitoring in the early postoperative period in patients having undergone a pulmonectomy]. PMID- 11764589 TI - [Liver resection: course of the postoperative period and use of a somatostatin analog (sandostatin) for preventing complications]. PMID- 11764590 TI - [One-stage esophagoplasty with scar-changed stomach]. PMID- 11764591 TI - [Device for drainage in acute destructive pancreatitis]. PMID- 11764592 TI - [Cyst excision and reconstruction of extrahepatic bile ducts]. PMID- 11764594 TI - [On the article by Ia. P. Kulik and S. N. Pokoliukhin "Time for choice: preventive or curative appendectomy (view point)]. PMID- 11764593 TI - [Reconstruction of the urinary tract in an allogeneic kidney transplant recipient in the early postoperative period]. PMID- 11764595 TI - [Outstanding discovery of surgeon N. S. Korotkov]. PMID- 11764596 TI - The new genetics and cancer: the contributions of clinical medicine in the era of biomedicine. PMID- 11764597 TI - E. George Squier and the discovery of cranial trepanation: a landmark in the history of surgery and ancient medicine. PMID- 11764598 TI - Interpreting dreams for corrective regimen: diagnostic dreams in Greco-Roman medicine. PMID- 11764599 TI - The history of shit: an essay review. PMID- 11764600 TI - Tales from the gender universe: an essay review. PMID- 11764601 TI - Preventing and treating infections related to dental implant placement. Interview. PMID- 11764603 TI - Correcting a single-tooth anterior crossbite with lingual segmented mechanics. PMID- 11764602 TI - An indirect method for bonding lingual retainers. PMID- 11764604 TI - The modified Bluegrass appliance. PMID- 11764605 TI - 2001 JCO Orthodontic Practice Study. Part 1. Trends. PMID- 11764606 TI - An organic polymer orthodontic appliance. PMID- 11764607 TI - An easy-to-tie elastomeric module. PMID- 11764609 TI - White teeth. PMID- 11764608 TI - Micro-implant anchorage for lingual treatment of a skeletal Class II malocclusion. PMID- 11764610 TI - Shifting the balance of power. PMID- 11764611 TI - Occlusal caries: pathology, diagnosis and logical management. AB - Occlusal caries now accounts for most of the lesions in children aged 8-15 years. This paper presents a ranked visual scoring system for occlusal caries diagnosis. It relates the clinical appearance of the lesion to its activity, the level of infection of the dentine and the histopathology. The appropriate management for each score is suggested. PMID- 11764612 TI - Successful restoration of load-bearing cavities in posterior teeth with direct replacement resin-based composite. AB - Successful restoration of posterior teeth with resin-based restorative materials requires the clinician to be aware of the factors influencing success. These include correct patient and cavity selection, correct choice of material, identifying a matrix system that will achieve a tight contact, and correct placement methods. A means of avoiding stress due to polymerization shrinkage should also be used. PMID- 11764613 TI - Treatment planning for the problem patient: restorative, ethical, legal and psychological perspectives. Case 4: Mr Lester. AB - 'Mr Lester' is the final case study in a series of four articles that aims to look at some of the problems patients may present with when they visit their dentist. Each article starts with a brief scenario about the hypothetical patient and his/her clinical problems. As well as the clinical problem, each case also raises ethical, legal or psychological problems. All of these issues are discussed and possible management strategies and treatment options investigated. PMID- 11764614 TI - Internet service providers: choosing the right one. AB - In order to access the Internet it is necessary to open an account with an Internet Service Provider. This article describes the typical services provided by these companies so that the new subscriber will be in a better position to make an informed choice. PMID- 11764616 TI - Case study of an anxious child with extensive caries treated in general dental practice: financial viability under the terms of the UK National Health Service. AB - This case study describes the management of Callum, an anxious 7-year-old boy with extensive caries. Callum's dental care was carried out in a general dental practice in the North of England under the terms of the National Health Service. A preventive programme was carried out in conjunction with the restorative philosophy according to guidelines published by the Dental Practice Board in 1997. PMID- 11764615 TI - Drug-induced gingival overgrowth: a case with auto-correction of incisor drifting. AB - Drug-induced gingival overgrowth is an iatrogenic clinical condition, which affects a proportion of patients medicated for conditions such as hypertension, epilepsy and the prevention of organ transplant rejection. Clinical manifestation can vary in severity from minor problems to complete coverage of the standing teeth. Drifting of teeth can also occur, producing further aesthetic and functional problems for the patient. This report documents a case of a renal transplant patient in whom drifting of the upper incisor teeth spontaneously resolved following surgical reduction of the overgrown gingivae. Clinical issues relating to the management of gingival overgrowth are also discussed. PMID- 11764617 TI - The competent graduate. PMID- 11764619 TI - Basic life support update. PMID- 11764618 TI - House of Lords debate dental sedation. PMID- 11764620 TI - Letter from the Secretary. PMID- 11764621 TI - A rural dental practice. PMID- 11764622 TI - Periodontics: the state of the art. PMID- 11764623 TI - Effects of smoking on the prevalence and severity of periodontal disease. PMID- 11764624 TI - Oral and periodontal status in Sjogren's syndrome. AB - Sjogren's syndrome is a multi-system chronic inflammatory disease of the exocrine glands. Inflammation of the salivary glands leads to reduction in salivary output, which imposes a significant impact on oral health. Dentists and dental hygienists are the primary healthcare providers to identify early signs and symptoms of Sjogren's syndrome. Early diagnosis of Sjogren's syndrome is fundamental for effective management of the disease. PMID- 11764625 TI - Systemic disease and periodontal disease. PMID- 11764626 TI - Occlusal trauma--periodontal concerns. AB - While there is evidence that suggests that occlusal trauma is a risk factor for periodontal destruction, there is no evidence that indicates that occlusal trauma will initiate periodontal destruction. Effective plaque control and compliance with periodontal maintenance recommendations are key and essential factors necessary to assure successful treatment and control of periodontal disease. PMID- 11764627 TI - Esthetic implant dentistry. PMID- 11764628 TI - Periodontal plastic procedures in esthetic dentistry. PMID- 11764629 TI - Local drug delivery in the treatment of periodontitis. AB - The current data suggest that local delivery of antimicrobials into the periodontal pocket can improve periodontal health. However, they do not provide a superior result to scaling and root planing. In conjunction with scaling and root planing, the adjunctive use of local drug delivery devices may enhance the results in sites which do not respond to conventional therapy. PMID- 11764630 TI - Ethical issues of domestic violence. Response to ethical dilemma #37. PMID- 11764631 TI - Oral and maxillofacial pathology case of the month. Histoplasmosis. PMID- 11764632 TI - Access to dental care: a call for innovation. AB - For many Americans dentistry not only works but works very well. Most Americans receive the care that they need and want. However, dentistry's success has not been whole or uniform and it has not reached every corner of America. In a society as prosperous as our, it is incumbent upon us, as a profession to help make sure that dentistry's success is accessible to each and every American. While recent efforts to address dental services use disparities may result in some improvements, most likely no single national effort will be globally effective. New ideas, including innovations that are local in design and market sensitive, will be needed to make the kinds of improvements that are desired. PMID- 11764633 TI - Dental insurance: a purchaser perspective. AB - Principals in a dental health purchasing organization report their views and those of interviewed purchasers on dental insurance packages. Purchasers make their decisions in a market context, balancing cost with employee benefits needed to attract qualified employees. While having a dental plan is important, the financial and coverage details are not usually scrutinized by employees. Issues of access and freedom from hassle are important considerations. There is growing cynicism among purchasers that dentists are driven by a profit motive and a desire for attractive work hours. PMID- 11764634 TI - ADA Council on Dental Benefit Programs. PMID- 11764635 TI - An embarrassment of riches. PMID- 11764636 TI - A four-year curriculum in professional ethics and law for dental students. AB - The four-year sequence of ethics courses at the School of Dentistry, University of Detroit Mercy is described in this article. A course blending lectures and small group discussion is taught each year, focusing on the issues facing students relevant to the students' stage of professional development. The sequence concludes with an Ethics Round in which students present a personal patient-based ethics case. PMID- 11764637 TI - Does this integrated law and ethics curriculum promote ethical thinking? AB - In an invited response, the Detroit Mercy, School of Dentistry combined ethics and law four-year curriculum is analyzed. Previous models combining law and ethics have shown more success in the former than the latter. Additional concerns include the lack of an explicit measure of ethical outcomes such as moral reasoning and the assumption that ethical activities engaged in by novices such as the White Coat Ceremony and early written assignments demonstrate competence. PMID- 11764638 TI - Informed consent: direct posterior composite versus amalgam. AB - Survey data were obtained from 144 dentists and 116 patients concerning their attitudes and preferences toward direct composite and amalgam restorations in the posterior segment. Some dentists report that they take the initiative in recommending direct composites in these cases and others report that patients request them. Selection criteria for direct composite posterior restorations are similar to those advocated in the dental literature. Those characteristics of alternative materials emphasized in obtaining informed consent mirror the characteristics of the materials dentists report most often performing. Patients report an interest in tooth-colored restorations and trust dentists' professional opinion, but also express a strong desire for full information as part of informed consent. PMID- 11764639 TI - Fellowship process insights-- American College of Dentists. PMID- 11764640 TI - Technology innovation. AB - Technology is the way dentistry is practiced--the materials and methods, characteristics of the dentist and staff, and nature and values of patients. Innovation is a conscious process of improving that technology. Dentists, not researchers or manufacturers, are the source of most innovation in dentistry. Characteristics such a innate curiosity, sophistication, discretionary income, and practice isolation contribute to innovativeness. Innovation diffusion has a characteristic S-shape, with few early and late adopters and a rapid spread in the middle phase. Much is known regarding the personality and behavior of early and late adopters and those types of innovations that are likely to diffusion rapidly. PMID- 11764641 TI - The impact of insurance on oral health. AB - Evidence from correlation and experimental studies supports the view that availability of dental insurance increases both utilization of services and oral health. These effects are most pronounced for individuals with middle or low incomes--those most in need of care. Defining optimal levels of care and the most effective distribution of resources remains, however, an evolving and still unanswered question. PMID- 11764642 TI - The conservative management of a large odontogenic keratocyst by decompression and enucleation. PMID- 11764643 TI - Staphylococcal submandibular lymphadentitis of childhood. AB - The presentation of two patients with the condition is described. The difficulty of finding an underlying cause of the infection is discussed, and the importance of a history of recent head and neck infection emphasised. Recommendations are made for appropriate antibiotic therapy to cover Staphylococci as well as the more common Streptococci. PMID- 11764644 TI - [Neurobiological correlates premeditated (learned) aggression: seeking new experimental approaches]. AB - Theoretical possibility of experimental modeling of learned (premediated) aggression developing in human after experience of aggression is considered. The sensory contact technique increases aggressiveness in male mice and allows aggressive type of behavior to be formed as a result of repeated experience of victories in daily agonistic confrontations. Some behavioral domains confirm the development of learned aggression in males similar to those in humans. The features are: repeated experience of aggression reinforced by victories; elements of learned behavior after period of confrontations; intent, measured by increase of the aggressive motivation prior agonistic confrontation; decreased emotionality estimated by parameters of open field behavior. Relevant stimuli provoke demonstration of aggression. This review summarized data on the influence of positive fighting experience in daily intermale confrontations on the behavior, neurochemistry and physiology of aggressive mice (winners). This sort of experience changes many characteristics in individual and social behaviors, these having been estimated in different tests and in varied situations. Some physiological parameters are also changed in the winners. Neurochemical data confirm the activation of brain dopaminergic systems and functional inhibition of serotonergic system in winners under influence of repeated experience of aggression. The expression of the neurochemical and behavioral changes observed in winners has been found dependent on the mouse strain and on the duration of their agonistic confrontations. Similarities in mechanisms of learned aggression in humans and mice are considered. PMID- 11764645 TI - [Current views on oxygen transport from blood to tissues]. AB - During the recent 25-30 years, sophisticated experiments and mathematical simulation significantly changed the generally accepted theory of oxygen transport in tissue, which was based on two major postulates, namely: 1) Blood flows in capillaries continuously at uniform velocity, 2) Gas circulation between blood and tissue takes place exclusively in capillaries. As was shown by modern research techniques, blood flow in microvessels has irregular sharp velocity fluctuations in very short time intervals (seconds). In addition, mean velocity of blood flow in microvessels of the same caliber and the same micro-region of tissue may differ several times. Therefore, efficiency of microcirculation reactions may be assessed exclusively witH mean blood velocity in capillaries of the whole micro-region, and with complicated changes of the histogram of mean velocity distribution in capillaries. It was shown that arteriolas and venulas of inactive muscles and brain account for 30 to 50% of gas circulation between blood and tissue. This resulted in fundamental change of the previous postulates in the area of tissue gas circulation physiology, and, in effect, in replacement of oxygen transport paradigm created by A. Krog. This study is an attempt to present a new modern concept of oxygen transport in tissue, to show its research significance, and possible applications. PMID- 11764646 TI - [Regulation and self-regulation of the pancreas secretion]. AB - A review of modern experimental and clinical research, including own author's data, on regulation of the periodical and postprandial external pancreas secretion and of the secretion phases. Focus on self-regulation of pancreas exosecretion with the pancreatic enzymes based on the principle of negative feedback, and on mechanisms of the feedback inhibition of pancreatic secretion. Description of the selective and generalised inhibition of secretion of pancreatic enzymes, the role of this mechanism in emergency adaptation of the fermental spectrum of the pancreas secretion in response to the nutritional composition and properties of the duodenal chemus. In conclusion, the experimental and clinical data are presented on use of intraduodenal injection of trypsin as a generalised inhibitor of pancreas secretion in case of acute pancreatitis. PMID- 11764647 TI - [Homeostasis in the gastric mucosa and blood circulation. Part 1. Mechanisms of the adequate blood flow maintenance in the gastric mucosa]. AB - The increase of mucosal blood flow in response to food entrance into stomach or different irritant action is the component of gastric mucosal defence barrier. Sufficient blood flow ensures normal acid-bicarbonate balance in gastric mucosa, supports the healing process and prevents superficial damages from developing into deep ones. Capsaicin-sensitive afferent nerve fibers play the large role in the blood flow regulation. The influence of these nerve fibers on the gastric blood flow is mediated by the calcitonin-gene related peptide. This peptide released from peripheral afferent terminals improves microcirculation in stomach walls. Moreover nerve impulses from afferent neurons modulate parasympathetic activity that in turn induces the increase of gastric mucosal blood flow through both choilinergic and noncholinergic mechanisms. The gastric mucosal blood flow may be also regulated by humoral and paracrine metabolites. Nitric oxide and prostaglandines are the most important low molecular weight compounds. They play the main role in the maintenance of the basal gastric mucosal blood flow and in the development of hyperemic responses to harmful agents. PMID- 11764648 TI - [Interrelations between sympathetic adrenal and opioid systems--regulatory mechanism determining cardiac resistance to stress damage]. AB - The present paper has analyzed relationship between sympatico-adrenal and opioid systems in the pathogenesis of stress heart damage. Based on the our own results and other investigator data the authors make a conclusion that namely relationship between opioid and sympatico-adrenal systems both on the level of the brain and on the periphery determines a degree of the heart resistance to the injury action of severe stress. Myocardial protection by opioids at stress was found to be mediated by the peripheral mu-opioid receptors and was associated with decrease in an activity of sympatico-adrenal system and a inhibition of its effector part. On contrary central opioid system activation leads to an increase in stress heart damage via an increase in sympathetical influence on the myocardium. PMID- 11764650 TI - Acute radiation effects in normal tissues--translational aspects of biological research. PMID- 11764649 TI - [Ideas of V N Chernigovskii important for integration of physiology and clinical neurology]. PMID- 11764651 TI - Radioprotection of head and neck tissue by amifostine. PMID- 11764652 TI - Cytohormonal status and acute radiation vaginitis. PMID- 11764653 TI - A study of high frequency ultrasound to assess cutaneous oedema in conservatively managed breast. PMID- 11764654 TI - Intensity-modulated radiotherapy reduces lung irradiation in patients with carcinoma of the oesophagus. PMID- 11764655 TI - Impaired sphincter function and good quality of life in anal carcinoma patients after radiotherapy: a paradox? PMID- 11764656 TI - Normal tissue reactions after linac-based radiosurgery and stereotactic radiotherapy. PMID- 11764657 TI - Fitting of tissue tolerance data to analytic function: improving the therapeutic ratio. AB - Response of human tissues to ionizing radiation is a complex process. It is influenced by many factors, such as use of chemotherapy drugs and underlying diseases such as diabetes and/or lung emphysema. A phenomenological model such as Lyman's is an attempt to predict the complication, for a variety of tissues, in the absence of these factors. The use of the model requires the knowledge of the parameters to predict the response for a specific endpoint. Clinical response data are needed to determine these parameters. Emami et al. [6] have provided some data, based on pre-CT and pre-3-D information, for some of the most serious complications. Based on this information the parameters were determined [4]. However, to validate and further improve the predictive power of the model, improved clinical response data are needed. With CT-based 3-D treatment planning systems the dose-volume information is routinely produced. Efforts by the radiation oncology community are needed to collect this information and correlate it with the clinical outcomes in a uniform and systematic way, not only for the most serious complications but also for less severe radiation-induced complications that are routinely considered in radiation therapy. Also, the information about the tissue response with underlying disease and drugs will be useful. The use of NTCP for plan comparison is useful. However, the incorporation of TCP and NTCP for designing the plan is remarkable. A plan can be optimized for the best outcome for the patient. It is hoped that as the models and parameters are refined and predictive power of the model increases, better plans will be produced, significantly improving the therapeutic ratio. PMID- 11764658 TI - Intensity modulation techniques for improvement of normal tissue tolerance. PMID- 11764659 TI - Functional evaluation of the human pancreas before and in the early period after hyperfractionated accelerated radiochemotherapy. PMID- 11764660 TI - How the game is played--challenge between therapeutic benefit and acute toxicity in fractionated radiotherapy. PMID- 11764661 TI - Side effects in multimodal treatment concepts in carcinomas of the head and neck. PMID- 11764662 TI - Clinical side effects after radical prostatectomy. PMID- 11764663 TI - Prostate cancer--the Royal Marsden conformal experience. PMID- 11764664 TI - Comparison of early pulmonary changes in 18FDG-PET and CT after combined radiochemotherapy for advanced non-small-cell lung cancer: a study in 15 patients. PMID- 11764666 TI - Physical and psychosocial rehabilitation of cancer patients. PMID- 11764665 TI - Efficacy and quality of life outcomes of epoetin-alpha in a double-blind, placebo controlled, multicentre study of cancer patients receiving non-platinum containing chemotherapy. PMID- 11764667 TI - Personal and institutional liability. PMID- 11764668 TI - Radiotherapy-related fatigue and exercise for cancer patients: a review of the literature and suggestions for future research. PMID- 11764669 TI - Long-term side effects of radiotherapy in survivors of childhood cancer. PMID- 11764670 TI - Normal tissue reactions during and after radiochemotherapy. PMID- 11764671 TI - Gemcitabine (Gemzar) and radiotherapy--is it feasible? PMID- 11764672 TI - Secondary malignancies after multimodality treatment regimens. PMID- 11764673 TI - Experimental radiotherapy of late-responding tissues--recent advances and future development. PMID- 11764674 TI - Long-term effects of platin and anthracycline derivatives and possible prevention strategies. PMID- 11764676 TI - Scores and grades: a sampling of how college students and food safety professionals interpret restaurant inspection results. AB - Controversy surrounds the use of posted restaurant inspection scores and grades. There is much debate about how well a score or grade conveys risks to potential diners, and questions remain about how the public interprets posted scores and grades, regardless of how they are derived. To determine how such scores and grades are perceived, the authors surveyed a sample of Maryland college students and food safety professionals about what a posted inspection score of 86 means and what a letter grade of C means. There was no clear consensus about the meaning of the scores and grades described in the surveys. The majority of respondents felt that a restaurant should be either open or closed, and that the public should not have to decipher the meaning of a posted sign. The response of the sample is especially significant given that many respondents claimed that they would not eat at a restaurant with either a posted letter grade of C or a posted score of 86. Although these results do not come from a random sample, they nevertheless suggest that the public has a limited understanding of such signs and, at the same time, bases dining decisions on them. Thus, environmental health professionals must carefully consider how the public can be better educated about signs, how the signs can be less ambiguous, and whether posted restaurant inspection results are even advisable in their current form. PMID- 11764675 TI - Normal tissue reactions in radiotherapy and oncology. Introduction. PMID- 11764677 TI - Using GIS and demographics to characterize communities at risk: a model from ATSDR. PMID- 11764678 TI - Sources of the eutrophication problems associated with toxic algae: an overview. AB - Blooms of cyanobacteria (toxic blue-green algae) can produce health and environmental hazards in water, including water used for drinking or recreational purposes. How, why, and when these blooms are produced, as well as how to deal with them, are questions whose answers are vital to the safeguarding of public health in regions where the algae occur. The blooms are linked to eutrophication of water, and this paper discusses the eutrophication problems, their nature, and their relevance to the production of cyanobacteria. Nutrient limitations on algal productivity are considered, as is the involvement of the atmosphere, the storage of nutrients in soils, and the influence of anthropogenic activity. PMID- 11764679 TI - The art of Aspergillus and Penicillium speciation. PMID- 11764680 TI - Thermometers used for regulatory compliance. PMID- 11764681 TI - The killing fields: more foot-and-mouth lessons from the United Kingdom. PMID- 11764682 TI - Protecting children from ultraviolet radiation--information from the World Health Organization. PMID- 11764683 TI - An outbreak of Norwalk-like viral gastroenteritis in a frequently penalized food service operation: a case for mandatory training of food handlers in safety and hygiene. AB - In 1999, in Toledo, Ohio, an outbreak of gastroenteritis occurred among people who had attended a Christmas dinner banquet and had eaten food prepared by a local caterer. Overall, 93 of the 137 attendees (67.9 percent) reported illness. Eight sought medical care, and one was hospitalized. Case-control studies revealed that the illness was associated with eating tossed salad (odds ratio [OR] = 2.5, 95 percent confidence interval [CI] = 1.02-6.26). Eleven of 12 stool specimens that were taken from ill people tested positive for a Norwalk-like virus (NLV) but were negative for E. coli O157:H7, Salmonella, and Shigella. The primary source of the outbreak was not determined, but an infected food handler may have played a role in the transmission of the virus. The catering facility had been cited frequently for food safety and hygiene violations. None of the personnel or food handlers at this facility had been appropriately trained in safe food-handling practices, nor had the personnel at another local caterer that had prepared food items suspected of causing a multistate outbreak of NLVs. In Toledo, food service operations with trained personnel/food handlers received better inspection reports than food service operations without trained personnel and were less likely to contribute to foodborne outbreaks. Training of personnel and food handlers may be important for preventing outbreaks. PMID- 11764684 TI - [The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels]. AB - The authors investigated the effect on pH of the aqueous humour in man (collected before surgery of senile cataract, where the pH of the aqueous humour was within the range of 6.80-7.46 (7.11 +/- 0.11), after administration of antiglaucomatic drugs with a different concentration and pH (0.005% Xalatan--pH 6.43, 0.5% Timoptol--pH 6.80, 1% Pilocarpine--pH 5.87, 2% Trusopt--pH 5.33) under conditions in vitro. All mentioned antiglaucomatic drugs immediately reduced the pH of the aqueous humour towards acid values in the following order: Trusopt-Xalatan Pilocarpine-Timoptol. pH changes of aqueous humour after addition of Timoptol, Xalatan, Pilocarpine have the same course in time, and shift to alkaline pH values. The pH of aqueous humour after addition of Trusopt reached only during the 240th minute levels of the control aqueous humour. The pH values after all antiglaucomatic drugs did not change between 240 minutes and 24 hours. As regards the rate of activity and extent of effect in conjunction with the time when the pH of the control aqueous humour was attained the authors recorded the following order: Pilocarpine-Timoptol-Xalatan-Trusopt. PMID- 11764685 TI - [Comparison of visual function in myopia over -6.0 dpt after photorefractive keratectomy and laser in situ keratomileusis]. AB - 1. 41 myopes undergoing PRK and 31 patients undergoing LASIK for correction of spherical refractive error were examined before and 1, 3, 6 a 12 months after surgery on Schwind Multiscan with ablation zone between 5 and 7 mm. Mean preoperative spherical equivalent of refraction was -8.0 +/- 1.7 D in PRK group and -9.2 +/- 2.1 D in LASIK one. 2. Contrast sensitivity (CS) was tested on a computerized system of the Contrast sensitivity 8010 type in 6 spatial frequencies (0.74; 1.97; 3.69; 7.39; 14.77; 29.55 c/deg) and the best corrected visual acuity (BCVA) was measured on the normalized charts with Landolt rings. 3. At 12 months postoperatively, mean spherical equivalent of refraction was -0.6 +/ 1.0 D (PRK) and -1.0 +/- 0.8 D (LASIK). A refractive error within +/- 0.5 D had 31.5% (PRK) and 57.5% (LASIK) patients. Increasing of BCVA was measured in 51.5% (PRK) and 41.9% (LASIK) patients about 1 optotype to 2.5 lines. Mean CS in 6 frequencies reached 99.4; 102; 105; 109; 115 and 140% of preoperative values in PRK group and only 96; 95.8; 96.3; 95.8; 97.8 and 94.6% in LASIK one. 4. At 12 months after surgery, mean spherical equivalent, CS was better and number of patients with increased BCVA was significantly higher after PRK, than those attained with LASIK. On the other hand, a number of patients with a refractive error within +/- 0.5 D was higher and percentage of reoperations was lower in LASIK group. PMID- 11764686 TI - [Radiotherapy of age-related macular degeneration]. AB - The authors evaluate results of the radiotherapy by age-related macular degeneration. They have been performed in Department of Ophthalmology of Teaching Hospital of Charles University in Hradec Kralove from February 1999 to June 2000. Our group consisted of 23 patients (23 eyes), 10 males and 13 females in age from 41 to 83 years, with average of 69 yrs. They were evaluated 6 months after begin of radiotherapy. The patients were divided into 2 groups. 11 patients with the entry visual acuity 6/60-6/24 and 12 patients with the entry visual acuity 0.25/50-3/50. The study proved the fact that it is possible to treat the exudative form of age-related macular degeneration using radiotherapy. PMID- 11764687 TI - [An indirect carotid-cavernous fistula complicated by secondary glaucoma. Case report]. AB - The authors present clinical picture, diagnostic procedures and therapy of the dural shunt syndrome which is very often the cause of diagnostic difficulties. They report about unusual complication--secondary angle closure glaucoma and venous stasis retinopathy from thrombosis of ophthalmic vein and about the possibilities of the therapy. PMID- 11764688 TI - [Microsurgical treatment of posterior capsule opacification]. AB - PURPOSE: To evaluate irrigation/aspiration and posterior capsulectomy in the treatment of the posterior capsule opacification (PCO). SETTING: Department of Ophthalmology, School of Medicine, Comenius University, Bratislava, Slovakia. MATERIAL AND METHODS: Between 1.1.1999 and 31.7.2000 we treated 75 patients (79 eyes) for PCO. Cataract surgery was performed in the years 1990-1999. The artificial intraocular lens (IOL) was implanted in 62 eyes. The interval between cataract surgery and PCO surgery ranged from 4 m.-10 y. The regenerative type of PCO was present in 41, fibrotic in 23 and combined in 15 eyes. Irrigation/aspiration (I/A) was performed in 44 eyes. Capsulectomy with a vitrectomy probe was performed in 35 eyes. I/A procedure was 42x performed with a bimanual system. Capsulectomy was performed in combinations of various insertions of the infusion line (without, anterior chamber maintainer-AChM, pars plana) and capsulectomy (limbal or pars plana approach). It was evaluated: occurrence of peri- and postoperative complications; achieved best corrected visual acuity. RESULTS: Complications during I/A: posterior capsule tearing with vitreous prolaps 4x, IOL subluxation 3x, partial zonular dialysis 2x-1x with vitreous prolaps. During capsulectomy performed through the limbus was observed vitreous prolaps in two eyes. After capsulectomy, performed through pars plana without infusion line, was observed the chronical corneal oedema in one eye. The best corrected visual acuity improved for 2 and more lines in 79.5% of eyes after I/A procedure and in 74.3% of eyes after capsulectomy. The achieved visual acuity lower then 6/60 was caused by changes not related to the cataract and PCO surgery. After testing of various combinations, the most suitable capsulectomy procedure seems to be: infusion line through the limbus, capsulectomy through the radial scleral tunnel incision. In this fashion it is possible to perform the procedure as no-stitch surgery. CONCLUSIONS: Instead of possibility of occurrence of various peri- and postoperative complication after I/A and capsulectomy used for treatment of PCO these procedures complete possibilities in the treatment of PCO. For the regenerative type of PCO is suitable I/A procedure. For the fibrotic type of PCO is suitable capsulectomy through pars plana with AChM. By this procedure it is possible to remove also nearly all vitreous opacities. PMID- 11764689 TI - [Retinal vascular complications in systemic lupus erythematosus]. AB - An analysis of three women with retinal vaso-occlusive disease in systemic lupus erythematosus produced evidence for this most severe ophthalmic complication during the acute phase of the syndrome. Vaso-occlusive retinopathy appeared 5 years after the onset of systemic symptomatology in all of them. Association of central nervous system lupus and circulating anti-coagulants with increased occurrence of severe retinal vaso-occlusive disease are the subject of the present report. Unilateral extensive photocoagulation of two cases appeared to result in successful therapy of neovascular glaucoma after the central retinal artery occlusion in one patient. Lupus erythematosus is very serious systemic and ocular disease also in present time. PMID- 11764690 TI - [Retrospective study of histologically confirmed intraocular tumors at the Eye Clinic of the Vinohrady Faculty Hospital in Prague]. AB - The authors evaluated statistically in a retrospective study the histological findings of a total of 182 intraocular tumours assembled at the Ophthalmological Clinic, Vinohrady Faculty Hospital Prague in 1992-2000. The histological material was obtained from 147 patients by enucleation of the bulbus and in 35 patients by surgical resection. In 97.2% the authors proved the malignant character of the tumour. In 95% an uveal melanoma was involved. In malignant melanomas of the choroid the following parameters were investigated: site, size, histological type, state of Bruch's membrane and extrascleral propagation of tumour. In 67% the melanoma was in the choroid, in 21% in the ciliary body and in 12% in the iris. As to size, large and extremely large melanomas predominated (66%). Histologically melanomas of the mixed and spindle-cell type were most frequent (93%). Bruch's membrane was damaged in 48% melanomas. Transscleral extension of the tumour was present in 9% malignant choroid melanomas. PMID- 11764691 TI - [Frequency of removal of releasable sutures after trabeculectomy]. AB - PURPOSE: To find out the frequency and time of extraction of releasable sutures (RS) in the first and second operated eye. METHODS: In a retrospective study, 40 patients with primary open glaucoma were followed. Patients underwent trabeculectomy with two RS on both eyes. The trabeculectomy was performed by the same surgeon and by the identical method. RESULTS: It was not necessary to remove RS postoperatively in 30% of the first operated eyes and in 35% of the second operated eyes. One RS was removed in 37.5% of the first and 32.5% of the second eyes. Two RS were removed equally in 32.5% of both eyes. The differences of RS extraction on the first and on the second eye were not significant (p = 0.76). The extraction time was similar in both eyes, too. CONCLUSION: There is no difference between the first and second operated eye regarding the frequency and time of extraction RS. PMID- 11764692 TI - [Glaucoma drainage implants in the treatment of refractory glaucoma]. AB - The authors describe their experience with the first three glaucoma drainage implants. All patients had previously several antiglaucomatous operations and a greatly reduced vision. The intraocular pressure was resistant to conservative treatment. In all patients the authors recorded postoperative complications reported in the literature. Glaucoma drainage implants extend possibilities in patients with refractory glaucoma. PMID- 11764693 TI - [Opacification of the posterior lens capsule after extracapsular extraction--an outline of problems and potential therapy]. PMID- 11764694 TI - [Ludwig van Beethoven and his eyes]. PMID- 11764695 TI - Sources of information on healthy eating in a Mediterranean country and the level of trust in them: a national sample in a pan-European survey. AB - OBJECTIVE: To know the sources of information and the level of trust in these sources in a population to facilitate the promotion of healthy dietary habits. PATIENTS AND METHODS: A national survey was carried out according to an established protocol on a representative sample of 1009 Spanish subjects over 15 years of age selected by a random multietapic procedure. This study belongs to the Spanish partnership in a pan-European Survey about sources of information on healthy eating and their level of trust. The analysis was focussed on the evaluation of the 5 most frequently chosen sources. RESULTS: There was a trend towards a greater use and trust in "Health professionals" than other sources. Thus, about 26% of the respondents mentioning "health professionals" as the source of information on healthy eating. However, "TV/radio" (25.7%) was almost so often selected as "Health professionals". About 17.4% of subjects declared that they obtained no information at all on healthy eating. Subjects with university level of studies exhibited a greater mention of "Health professionals", while individuals belonging to higher socio-economic levels preferred "TV/radio". The degree of trust was higher for messages obtained from "Health professionals" (89.9%) and the "Department of Health" (78.7%) and lower for information obtained from "newspaper" (34.2%) and "advertising" (17.6%). CONCLUSION: Nutrition and health educators must promote dietary guidelines through the appropriate channels for communicating messages to different targets groups. PMID- 11764696 TI - [Supraventricular arrhythmia. Potential applications of esmolol]. AB - Atrial fibrillation, atrial flutter, paroxistical supraventricular tachycardias and atrial tachycardias are the main supraventricular arrhythmias. Atrial fibrillation is the most common. In this review we comment their physiopathology, clinical manifestations, and treatments, paying special attention to the possible esmolol applications. PMID- 11764697 TI - [Diabetes and surgery I: effects on metabolic control and preoperative evaluation]. AB - The management of diabetes mellitus before, during and after surgery represents a common challenge in clinical practice. Surgical stress promotes a sequence of hormonal changes that might cause devastating effects on the diabetic patient, and this stress depends on several factors, some of them predictable such as the type of surgical operation or the sort of anaesthesia which is applied. The glycemic control should be optimal in order to avoid the possible consequences derived from an inadequate metabolic control during the perioperative period. The knowledge of physiopathological processes involved in the effects of surgery and anaesthesia on metabolic control represents a key element for a successful management. PMID- 11764698 TI - [Implants of carotid body cells as a treatment alternative for Parkinson disease]. AB - The appearance of motor fluctuations and dyskinesias in a large number of parkinsonian patients treated with levodopa, has promoted the development of new therapeutical approaches. Deep brain stimulation of subthalamic nucleus and globus pallidus medialis results in a marked improvement of parkinsonism and levodopa-induced dyskinesias. However, this approach does no delay the progression of the disease. Transplantation of dopamine-releasing cells might represent an advantage as these cells could replace the loss of dopaminergic neurons occurring in Parkinson's disease. This article reviews the main results obtained in experimental models of Parkinson's disease and in humans using different types of dopaminergic cells. The advantages and limitations of this treatment are also discussed. PMID- 11764699 TI - [Transmissible spongiform encephalopathies: a scientific challenge for the new century]. PMID- 11764700 TI - [Person and medicine]. PMID- 11764701 TI - [Rofecoxib]. PMID- 11764702 TI - [Infection associated with intravascular catheter in 1998 at the University Clinic of Navarra]. AB - PURPOSE: To study the intravascular catheter related infections (CRI) since January of 1998 to January of 1999 in our hospital. METHODS: We studied 540 catheter tips using a modified combination of the cuantitative method of Cleri and the semicuantitative method of Maki. The catheters were classified into two groups according to the presence or absence of criteria for CRI. RESULTS: 74.5% of the retired catheters because of infection suspice did not satisfied criteria for CRI. 44.7% of the patients with criteria suffered a catheter-related bacteriemia while just 1.7% of the patients without criteria suffered a bacteriemia. The most common isolated microorganisms were coagulase-negative Staphylococci, Corynebacterium species and S. aureus. DISCUSSION AND CONCLUSIONS: At least, 74.5% of the patients with a suspice of catheter related infection could undergo a non invasive diagnosis procedure that would have showed that the catheter was not infected. PMID- 11764703 TI - Miscellaneous dental practice legal issues. PMID- 11764705 TI - The culture of survivorship. PMID- 11764704 TI - An introduction to snoring and sleep apnea for dental practitioners. PMID- 11764706 TI - The changing face of cancer survivorship. AB - OBJECTIVES: To provide a review of who is surviving cancer diagnosed within the last 20 years and key areas for research development related to cancer survivorship. DATA SOURCES: Articles, studies, and Surveillance, Epidemiology and End Results statistics. CONCLUSIONS: The information we have on today's survivors must be periodically revisited and revised to equip cancer patients with the knowledge and tools they need to master the new realities of their survivorship. IMPLICATIONS FOR NURSING PRACTICE: With the increasing numbers of individuals being cured of or living long periods of time following a diagnosis of cancer, oncology nurses who work with cancer survivors must maintain their knowledge of the issues and practices critical to the well-being of the patient. PMID- 11764707 TI - Late effects of cancer and its treatment. AB - OBJECTIVES: To review the common physical and psychosocial late effects of treatment in adult and childhood cancer survivors. DATA SOURCES: Published articles and research studies. CONCLUSIONS: More than half of individuals diagnosed with cancer can be expected to survive for more than 5 years. These survival gains have occurred because of more complex and multimodal therapy that may increase long-term toxicities. IMPLICATIONS FOR NURSING PRACTICE: Health care providers must be familiar with these late effects to offer preventive care and health promotion strategies to this patient population. PMID- 11764708 TI - Long-term persistence of symptoms. AB - OBJECTIVES: To provide a brief review of cognitive changes, fatigue, lymphedema, and peripheral neuropathy as persistent symptoms, and provide assessment and management information. DATA SOURCES: Published articles and research studies. CONCLUSIONS: As the number of people surviving cancer for extended periods of time continues to increase, the phenomenon of symptoms that persist following the completion of treatment is being recognized. IMPLICATIONS FOR NURSING PRACTICE: Research is needed to provide adequate knowledge about symptoms that persist following cancer treatment. PMID- 11764709 TI - Intimacy issues: sexuality, fertility, and relationships. AB - OBJECTIVES: To provide a review of the intimacy issues, (sexuality, fertility, and interpersonal relationships) that have an impact on the lives of cancer survivors. DATA SOURCES: Published articles, research studies, and textbook chapters. CONCLUSION: The experience of living with cancer impacts the survivors interpersonal relationships, sexuality, and fertility. As cancer treatments become more effective in prolonging life, options that preserve sexual function and fertility will be more prevalent. IMPLICATIONS FOR NURSING PRACTICE: It is the responsibility of the oncology health care professional to become educated about options that preserve sexual function and fertility and inform patients before treatment decisions are made. PMID- 11764710 TI - The past sets the stage for the future: follow-up issues facing long-term cancer survivors. AB - OBJECTIVES: To discuss current long-term follow-up management, the need for a long-term database, and creative strategies for follow-up care for cancer survivors. DATA SOURCES: Published articles, position statements, and personal experience. CONCLUSIONS: As the number of long-term cancer survivors increases, there needs to be a wellness-focused and organized approach to long-term follow up care. IMPLICATIONS FOR NURSING PRACTICE: The responsibility for developing, implementing, evaluating, and following up with long-term cancer survivors remains with the oncology and family practice staff. PMID- 11764711 TI - Transitional care for young adult survivors of childhood cancer. AB - OBJECTIVES: To review the obstacles and barriers to providing optimal care to young adult cancer survivors and discuss the transition from pediatric to adult health care system. DATA SOURCES: Published articles and textbook chapters. CONCLUSIONS: More than 70% of children diagnosed with cancer between birth and 14 years of age will be cured of their primary disease. Because of multiple physical and psychosocial risk factors imposed by their therapy and previous disease, childhood cancer survivors require life-long care. IMPLICATIONS FOR NURSING PRACTICE: Health care providers must be aware of the unique needs of these individuals for life-long follow-up and assist in facilitating this transition process. PMID- 11764712 TI - The end of the survival journey. AB - OBJECTIVES: To review the problems encountered by cancer survivors who face the end of their cancer journey. DATA SOURCES: Published review and research articles and textbook chapters. CONCLUSIONS: The experiences found at the end of the survivorship journey may be exacerbations of previously encountered symptoms and feelings. Achieving physical comfort replaces the goal of controlling the tumor. IMPLICATIONS FOR NURSING PRACTICE: Continued support is needed from the oncology health care team as expertise is sought from hospice or a palliative care team to provide a seamless transition in care. PMID- 11764713 TI - The meaning of illness to a long-term survivor. AB - OBJECTIVES: To review the ways in which cancer survivors find meaning in their illness experiences. DATA SOURCES: Research literature and professional and personal experiences. CONCLUSIONS: Survivors confront a number of issues as they try to find a place for their cancer experience in their lives and adopt different approaches to cope with their survivorship. IMPLICATIONS FOR NURSING PRACTICE: Nurses can assist cancer survivors to find meaning in their illness experience by understanding the symptoms and issues associated with survival. PMID- 11764714 TI - An advocate's perspective on cancer survivorship. AB - OBJECTIVE: To illustrate the scope of advocacy in cancer survivorship and to emphasize the critical role that health care providers play to help improve the quality of life of cancer survivors. DATA SOURCES: Published articles, government reports, and books. CONCLUSIONS: The delivery of quality cancer care requires not only an understanding of cancer survivorship issues but also a strategy for advocacy efforts for cancer survivors and their families. IMPLICATIONS FOR NURSING PRACTICE: Advocacy efforts involve individual interventions and family focused support, public and professional education, and programs and policies that enhance cancer care and quality of life. PMID- 11764715 TI - Toward comparable nursing data: American Nurses Association criteria for data sets, classification systems, and nomenclatures. AB - The American Nurses Association has long recognized the need for nursing to participate in the development of national healthcare data sets and standardized terminologies suitable for implementation in computer-based systems. In 1989, the American Nurses Association Steering Committee on Databases to Support Clinical Nursing Practice was established to make policy recommendations related to nursing data needs. A primary function of the committee was the development of criteria for "recognition" of nursing language systems toward the goal of a Unified Nursing Language System. The committee has evolved and, in 1998, was renamed the Committee on Nursing Practice Information Infrastructure. In this article the revisions in the American Nurses Association recognition criteria and the role of professional associations in standards development are discussed. Distinct criteria for nursing data sets, classification systems, and nomenclatures are reflective of the evolution in the healthcare environment toward concept-oriented terminologic systems that facilitate data re-use. PMID- 11764716 TI - A study of factors related to the use of online resources by nurse educators. AB - A descriptive cross-sectional survey was used to collect data from nurse educators related to the use of online electronic resources for scholarly pursuits. The 35-question survey was divided into 4 sections, Environment, Stressor, Utilization, and Demographics information. Two open-ended questions were also included to allow respondents to elaborate on factors that they believed facilitated or detracted from use of online resources but were not adequately covered in the survey. Data were received from 489 respondents who were faculty members currently teaching in 1 of 38 colleges or universities located in the 6 New England states offering a minimum of a baccalaureate degree in nursing. Quantitative and qualitative data analysis revealed that many of the same issues, previously reported as deterrents to the use of computers, also play a significant role in preventing the use of online resources. The two open-ended questions provided clarification of facilitators and detractors to use of online resources and were used to understand better the quantitative results. Based on the findings of this study, recommendations for administrators, educators, staff developers, and technical support personnel are discussed. PMID- 11764717 TI - Homebound older adults' experiences with the Internet and e-mail. AB - The purpose of this study was to explore homebound older adults' experiences with the Internet and e-mail employing the Dutch phenomenological approach. A sample of 5 homebound older adults was included. All participants were interviewed twice. Data were analyzed employing the technique recommended by Dutch phenomenologists. The analysis resulted in a total of 10 shared themes and a thick description of the homebound older adults' experiences with the Internet and e-mail. The findings indicated that all participants were faced with various challenges in learning the Internet and e-mail. Those difficulties, however, were overcome by continuous practice and support from various sources. Ultimately they found that the Internet and e-mail were excellent sources of support and enjoyment, resulting in an improved quality of life. PMID- 11764718 TI - Animal models in bacteriology. PMID- 11764719 TI - Animal models in virology. PMID- 11764720 TI - Animal models in parasitology. PMID- 11764721 TI - Animal models in mycology. PMID- 11764722 TI - The use of animal models in the development of classical vaccines. PMID- 11764723 TI - Revealing the spatiotemporal patterns of bacterial infectious diseases using bioluminescent pathogens and whole body imaging. PMID- 11764724 TI - Alternatives to animal testing in microbiology and infectiology. PMID- 11764725 TI - Animal testing in infectiology. Introduction. PMID- 11764726 TI - Enterohemorrhagic Escherichia coli. PMID- 11764727 TI - Staphylococcus aureus and Staphylococcus epidermidis: emerging pathogens in nosocomial infections. PMID- 11764728 TI - Enterococci. Habitats, infections, virulence factors, resistances to antibiotics, transfer of resistance determinants. PMID- 11764729 TI - Legionellosis, a disease transmitted by technical vectors. PMID- 11764730 TI - Bordetella pertussis: increasing problems with a well-known pathogen and its relatives. PMID- 11764731 TI - Tropheryma whippelii and the (re)emergence of an old disease. PMID- 11764732 TI - Campylobacter jejuni. PMID- 11764733 TI - The changing image of mycoplasmas: from innocent bystanders to emerging and reemerging pathogens in human and animal diseases. PMID- 11764734 TI - Gram-negative plant pathogenic bacteria. PMID- 11764735 TI - The new biology and drug research. PMID- 11764736 TI - Burkholderia/Stenotrophomonas. PMID- 11764737 TI - Helicobacter pylori. PMID- 11764738 TI - Biology and clinical significance of chlamydiae. PMID- 11764739 TI - Borrelia burgdorferi s.l., the infectious agent of Lyme borreliosis. PMID- 11764740 TI - Streptococcus pyogenes. PMID- 11764741 TI - Emerging bacterial pathogens. Preface. PMID- 11764742 TI - Commentary: seclusion practice in a Canadian forensic hospital. PMID- 11764744 TI - Compensation monitor. Pay scales suggest that Mom was right. PMID- 11764743 TI - Trying to get control of drug costs, Florida earns kudos--and a lawsuit. PMID- 11764745 TI - Some over-the-counter advice on making drug therapy work. Interview by Patrick Mullen. PMID- 11764746 TI - [Ebstein's anomaly and WPW syndrome]. PMID- 11764747 TI - In vitro toxicology in the light of new technologies. PMID- 11764748 TI - The G.B. Morgagni Medal 2000. PMID- 11764749 TI - Referral of Dr. Peter Mansfield to the GMC. Health authority has no power. PMID- 11764750 TI - Referral of Dr. Peter Mansfield to the GMC. Health authority made right decision. PMID- 11764751 TI - Referral of Dr. Peter Mansfield to the GMC. Should decision on vaccination be best for you or us? PMID- 11764752 TI - Referral of Dr. Peter Mansfield to the GMC. Doctors seem to have to march in step. PMID- 11764753 TI - Referral of Dr. Peter Mansfield to the GMC. Referral constitutes abuse of power. PMID- 11764754 TI - How best to organise acute hospital services? Models of healthcare delivery need to be compared in trials. PMID- 11764755 TI - How best to organise acute hospital services? Realtime teleneurology can help small hospitals. PMID- 11764756 TI - How best to organise acute hospital services? Kidderminster is ideal site for pilot trial. PMID- 11764757 TI - How best to organise acute hospital services? Radical thinking already exists in Kidderminster. PMID- 11764758 TI - Acupuncture for treatment for chronic neck pain. Reanalysis of data suggests that effect is not a placebo effect. PMID- 11764759 TI - Vaginal delivery after caesarean section. Study's focus on induction v spontaneous labour neglects spontaneous deliver. PMID- 11764760 TI - Vaginal delivery after caesarean section. Safety of single-layer suturing in caesarean sections must be proved. PMID- 11764761 TI - Is pain-related fear a predictor of somatosensory hypervigilance in chronic low back pain patients? AB - Pain-related fear has been found to be associated with increased disability and increased pain perception in patients with chronic low back pain. A possible mechanism by which pain-related fear could lead to increased pain perception is heightened attention to somatosensory sensations. In the present study, chronic pain patients reporting either a high or low level of pain related fear and control participants performed an auditory reaction time task, while occasionally non-painful electrical stimuli--accompanied by threatening instructions--were given to the arm or back. In the primary task condition, participants had to perform the auditory task while ignoring the electrical stimuli. Next, the task was presented under dual task conditions in which participants had to respond both to tones as well as to detection of electrical stimuli. It was hypothesized that for the primary task, high fearful patients would show greater disruption of performance on the auditory task than low fearful patients and controls when stimuli were presented to the back. For the dual task, slower reaction times for the auditory task, in combination with faster detection of electrical stimuli was expected. The hypotheses were not confirmed but patients scoring high on pain related fear did show an overall increase in reaction time for all conditions of the primary task, with or without simultaneous stimulation. Regression analyses demonstrated that high pain-related fear was associated with increased reaction time to tones both in patients and healthy controls, and that within patients pain-related fear was a better predictor of reaction time to tones than present pain intensity. The findings may be interpreted as showing that patients with elevated levels of pain-related fear habitually attend to somatic sensations, giving less priority to other attention-demanding tasks. PMID- 11764762 TI - Relative efficacy of different distillery effluents on growth, nitrogen fixation and yield of groundnut. AB - A field experiment with groundnut as test crop was conducted to evaluate the manurial potential of three distillery effluents: raw spent wash (RSW), biomethanated spent wash (BSW) and lagoon sludge (LS) vis-a-vis recommended fertilizers (NPK + farm yard manure (FYM)) and a control (no fertilizer or distillery effluent). It was found that all the three distillery effluents increased total chlorophyll content, crop growth rate (CGR), total dry matter, nutrient uptake (N, P and K) and finally seed yield compared to the control but inhibited nodulation and decreased nitrogen fixation. Among the three distillery effluents, BSW produced the highest seed yield (619 kg ha(-1)) twice that of control (3.10 kg ha(-1)), followed by RSW (557 kg ha(-1)) and LS (472 kg ha(-1)). However, the distillery effluents did not influence protein and oil contents. It was concluded that these distillery effluents because of their high manurial potential could supply nutrients, particularly potassium, nitrogen and sulphur, to the crops and thus reduce the fertilizer requirement of crops. Nevertheless, the crop performance and yield with three distillery effluents were overall less than that produced by recommended NPK + FYM probably on account of failure of the effluents to supply balanced nutrition to the plants for achieving their potential growth capacity. PMID- 11764763 TI - Chemical characteristics of Malian and Belgian solid waste composts. AB - Two composts, a Malian (C1) and a Belgian (C2), and a peat substrate (C3) were analyzed for their suitability for land application. The results revealed that the materials can be used in agriculture but only the composts can supply all macro-nutrients necessary for plant growth. The fractionation of Mn, Fe, Zn and Cu in operationally defined fractions (water soluble, exchangeable, complexed, organically bound and residual) allows estimation of the availability of metals for uptake. For example, 16% of the total Mn in the composts (C1 and C2) and 22% in the peat substrate would be plant available. Available Fe in the three materials was less than 2%. Available Zn varied from 10% to 25%. The fractionation also allowed estimation of the potential for contamination of groundwater following the applications of composts to agricultural lands. PMID- 11764764 TI - Kinetics of acetyl coenzyme A: arylamine N-acetyltransferase from rapid and slow acetylator human benign prostatic hyperplasia tissues. AB - N-acetyltransferase (NAT) activity was determined in 40 human benign prostatic hyperplasia tissues using 2-aminofluorene (AF) and p-aminobenzoic acid (PABA) as substrates. These were then assayed by high performance liquid chromatography for determining the amounts of acetylated AF and PABA and non-acetylated AF and PABA. The activities (mean +/- SD) of AF-NAT from human benign prostatic hyperplasia tissues were divided into rapid (2.06 +/- 0.08 nmol/min per milligram protein), intermediate (1.25 +/- 0.26 nmol/min per milligram protein), and slow (0.58 +/- 0.30 nmol/min per milligram protein) acetylator groups. The activities (mean +/- SD) of PABA-NAT from human benign prostatic hyperplasia tissues were also divided into rapid (2.00 +/- 0.00 nmol/min per milligram protein), intermediate (1.25 +/- 0.18 nmol/min per milligram protein), and slow (0.48 +/- 0.29 nmol/min per milligram protein) acetylator groups. Kinetic constants for arylamine NAT activities were determined for each of these acetylator groups. Apparent differences in Km and Vmax for AF were found. Therefore, there seems to be a polymorphism in NAT activity with two rapid, five intermediate, and 33 slow acetylators among the 40 samples assayed. This is the first demonstration of acetyl CoA-arylamine NAT activity in human benign prostatic hyperplasia tissues. PMID- 11764765 TI - Molecular biology of peptide and polyketide biosynthesis in cyanobacteria. AB - Cyanobacteria produce numerous and structurally diverse secondary metabolites, in particular nonribosomal peptide and polyketide structures. Various bioactivities could be assigned to these compounds, and some may prove useful either for development into commercial drugs or as biochemical research tools. Microcystin, a worldwide common cyanobacterial hepatotoxin, was the first metabolite whose nonribosomal biosynthesis could be confirmed by knock-out mutagenesis. The microcystin synthetase complex consists of peptide synthetases, polyketide synthases, and hybrid enzymes, and reveals a number of novel enzymatic features, signifying the potential of cyanobacterial biosynthetic systems for combinatorial biochemistry. Recent studies have shown the presence of peptide synthetase genes and polyketide synthase genes within a number of cyanobacterial genomes. This knowledge may be very valuable for future screening projects aimed at the detection of new bioactive compounds. PMID- 11764766 TI - Chromoscopy during colonoscopy. PMID- 11764767 TI - Comparison of two methods for colonoscopy preparation. PMID- 11764768 TI - How can we measure insertion depth during the enteroscopic push procedure? PMID- 11764769 TI - Beta-lactamase-inhibitor combinations in the 21st century: current agents and new developments. AB - Combinations of beta-lactams and beta-lactamase inhibitors have become one of the most successful antibacterial strategies in our global battle against bacterial infections. The success of these agents is particularly emphasized by the continued efficacy of Augmenting (amoxicillin and clavulanate) after nearly 20 years of clinical use. The clinical situation now dictates that second-generation beta-lactamase inhibitors capable of encompassing both class A and class C beta lactamases would combat emerging resistance and provide a vital addition to our armory of hospital antibiotics. This realization has generated a renewed interest in beta-lactamase inhibitors and improved the prospects for the delivery of such agents in the future. PMID- 11764770 TI - Pharmacokinetics and pharmacodynamics of the new fluoroquinolones: focus on respiratory infections. AB - High occurrence of penicillin-resistant and multidrug-resistant Streptococcus pneumoniae and reports of resistance with Haemophilus influenzae and Moraxella catarrhalis are influencing the empiric treatment of community-acquired respiratory infections and allowing the new fluoroquinolones to serve as important treatment alternatives. Recent analysis of the pharmacokinetic and pharmacodynamic properties of the new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) have shown high bioavailability (> or = 70%) and long serum half-lives (> or = 7 h), allowing for once-daily dosing. They concentrate in respiratory tract tissues and fluids at levels that exceed serum concentrations. Concentration-dependant killing is evident and the pharmacodynamic parameters that best correlate with bacteriological eradication, clinical efficacy and minimization of resistance have now been identified. The new fluoroquinolones display excellent pharmacokinetic and pharmacodynamic properties against community-acquired respiratory pathogens, making them ideal agents for the empirical treatment of community-acquired respiratory infections. PMID- 11764771 TI - Glycylcyclines: third-generation tetracycline antibiotics. AB - Although tetracycline antibiotics have some roles in human and veterinary medicine, the widespread emergence of microbial resistance has severely limited their effectiveness. A new generation of tetracyclines, the glycylcyclines, is being specifically developed to overcome problems of resistance to earlier tetracyclines. One of the glycylcyclines, 9-t-butylglycylamido-minocycline (GAR 936, tigilcycline), is currently undergoing clinical trials and microbiological, pharmacodynamic and pharmacokinetic data have recently been presented for several glycylcyclines, including GAR-936. An ongoing concern is whether resistance to glycylcyclines might arise in the future. PMID- 11764772 TI - Oxazolidinones: a new class of antibacterials. AB - The oxazolidinones represent the first truly new class of antibacterial agents to reach the marketplace in several decades. They have a unique mechanism of action involving inhibition of the initiation step of protein synthesis and are not cross-resistant to other classes of antibiotics. The first marketed member of that class, linezolid (Zyvox), shows good efficacy with an impressive antibacterial spectrum (including activity against gram-positive organisms resistant to other drugs), and a pharmacodynamic/pharmacokinetic relationship best characterized by time above the minimum inhibitory concentration. The agent is effective by both the intravenous and oral route of administration. Although technically classified as bacteriostatic against a number of pathogens in vitro, linezolid behaves in vivo like a bactericidal antibiotic. PMID- 11764773 TI - Recent advances in the treatment of rhinovirus infections. AB - Rhinoviruses are the most common causes of viral respiratory infections and complications caused by viral respiratory infections in patients with underlying lung disease. Major recent therapeutic advances include the development of capsid function inhibitors (pleconaril), inhibitors of 3C protease (AG7088), and recombinant soluble intercellular adhesion molecule (sICAM)-1, all of which exhibit potent antirhinoviral activity in vitro and varying activity in clinical trials. Pleconaril and AG7088 have shown the most promise and are the most advanced in clinical trials. PMID- 11764774 TI - Therapeutic options for the management of influenza. AB - Over the past few years a novel class of antiviral agents, the neuraminidase inhibitors, has been found to be safe and effective in the prevention and treatment of influenza. Previously available agents, the M2 inhibitors amantadine and rimantadine, could only be used to treat influenza A infections and resistance develops rapidly. Zanamivir (Relenza) and oseltamivir (Tamiflu), the two clinically available neuraminidase inhibitors, are effective for treating both influenza A and B infections in adults and children and have also been shown to reduce the frequency of antibiotic-requiring complications of influenza infections. Inhaled zanamivir has shown benefit in treating acute influenza with mild to moderate underlying asthma or chronic obstructive pulmonary disease. Studies are needed to examine the use of these agents, alone or in combination with M2 inhibitors or ribavirin, in the management of severe infections in hospitalized patients and immunocompromised hosts. Studies are also needed to address other groups at increased risk for influenza complications, such as pregnant women and children below one year of age. PMID- 11764775 TI - Influenza vaccines: new developments. AB - Current inactivated influenza vaccines are being produced with three influenza virus strains that are recommended annually by the World Health Organization on the basis of information obtained from global influenza surveillance. The use of these vaccines, for which the antigens are produced in embryonated chicken eggs, can result in a significant reduction of influenza-related morbidity and mortality. Nevertheless, there is still a demand for vaccines with a higher efficacy that can be produced more rapidly and more flexibly in response to an epidemic or a pandemic. New developments in the field of influenza vaccine preparation include novel vaccine production technologies, reverse genetics technology for the generation of vaccine strains and novel adjuvants for the improvement of vaccine immunogenicity. PMID- 11764776 TI - Preventive and therapeutic strategies for respiratory syncytial virus infection. AB - Respiratory syncytial virus (RSV) remains an important cause of pneumonitis in infants and in the elderly and immunosuppressed. Passive immunoprophylaxis of high-risk infants with the humanised monoclonal antibody palivizumab reduces RSV related hospitalisation and admission to intensive care units by about 50%, although optimal and cost-effective use of this agent remains undefined. The development of an RSV vaccine is the focus of much research and recent advances with live attenuated vaccines are promising--several agents are in clinical trials. The value of the only therapeutic agent available to treat established infection, the antiviral ribavirin, is now seriously doubted and the agent is little used. New RSV chemotherapeutics are just entering clinical trials. PMID- 11764777 TI - Progress in HIV vaccine development. AB - Recent advances in HIV vaccine development include initiation of the first efficacy trials and substantial expansion of the preclinical pipeline. Several preclinical candidate vaccines have induced strong cellular immune responses and provided impressive protection against AIDS in non-human primate models; however, candidates that induce broadly neutralizing antibodies remain elusive. PMID- 11764778 TI - Proteomics: an holistic analysis of nature's proteins. AB - Proteomics has matured to a technology platform way beyond two-dimensional gel electrophoresis, delivering on its promise to identify structure, function and cellular localization of all proteins expressed in a cell at a given time. Major achievements in the past year include mapping the proteome of human and microbial cells, improvements in two-dimensional gel electrophoresis and mass spectrometric analysis, and the development of protein arrays and biochips. PMID- 11764779 TI - Fluorescent imaging in living systems. AB - The use of fluorescent imaging techniques in the study of living biological systems has become an important experimental tool in modern biology. Over recent years novel imaging technologies have been developed and older techniques refined. New fluorescent probes continue to become available and the ways in which they are used is increasingly creative. Commonly used imaging methods such as confocal and multiphoton microscopy, when combined with techniques such as fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM), can provide powerful strategies with which to study molecular events in intact cells. PMID- 11764780 TI - Reporter-gene systems for the study of G-protein-coupled receptors. AB - Reporter-gene assays offer an alternative to biochemical assays for following signal transduction pathways from receptors at the cell surface to nuclear gene transcription in living cells. Specific reporter-gene systems are now available for the study of ligand activity at G alpha(i/o), G alpha(s) and G alpha(q) G protein-coupled receptors. In recent years reporter genes have been applied in academia and industry to the study of ligand efficacy and affinity in recombinant and primary cell lines using a variety of colour, fluorescent or luminescent read outs. PMID- 11764781 TI - Cellular screening assays using fluorescence microscopy. AB - The recent development of automated fluorescence imaging systems has enabled fluorescence microscopy to be used for the purposes of compound screening. This information-rich technique has found various applications, including screening for the effect of kinase inhibitors on the cytoskeleton, agonist-stimulated receptor internalization, and protein phosphorylation and acetylation. The discovery of novel fluorescent proteins and new fluorescent dyes will find many applications in multichannel fluorescence imaging assays. PMID- 11764782 TI - Nucleic acid and polypeptide aptamers: a powerful approach to ligand discovery. AB - Nucleic acid ligands against important targets in infectious, malignant and vascular diseases are continually being discovered by the process of in vitro evolution. Promising methods are being developed for the exploitation of these aptamers in biosensors and other diagnostic devices. Ribosome and mRNA display methods for isolating polypeptide aptamers from highly complex libraries have been developed and have the potential to widen the target range and utility of in vitro evolved ligands. PMID- 11764783 TI - Effect of feed intake on ovine hindlimb protein metabolism based on thirteen amino acids and arterio-venous techniques. AB - It has been suggested that protein synthesis in peripheral tissues: (1) responds in a curvilinear manner to increasing feed intake over a wide range of feeding levels; and (2) has a greater sensitivity to intake than protein breakdown. The aim of the present experiment was to test these hypotheses across the ovine hindlimb. Six growing sheep (6-8 months, 30-35 kg), with catheters in the aorta (two), posterior vena cava and jugular vein, received each of four intakes of dried grass pellets (0.5, 1.0, 1.5 and 2.5 x maintenance energy; M) for a minimum of 7 d. A U-13C-labelled algal hydrolysate was infused intravenously for 10 h and from 3-9 h para-aminohippuric acid was infused to measure plasma flow. Arterial and venous plasma were obtained over the last 4 h and the concentrations and enrichments of thirteen (13)C-labelled amino acids (AA) were determined by GC-MS. As intake increased, a positive linear response was found for plasma flow, arterial concentrations of the aromatic and branched-chain AA, total flow of all AA into the hindquarters and net mass balance across the hindquarters (except glycine and alanine). Based on two separate statistical analyses, the data for protein synthesis showed a significant linear effect with intake (except for phenylalanine, glycine and alanine). No significant curvilinear effect was found, which tends not to support hypothesis 1. Nonetheless, protein synthesis was not significantly different between 0.5, 1.0 and 1.5 x M and thus the 2.5 x M intake level was largely responsible for the linear relationship found. There was no significant response in protein breakdown to intake, which supports hypothesis 2. PMID- 11764784 TI - First AbioCor trial patient dies. PMID- 11764785 TI - Niacin-simvastatin combination benefits patients with coronary artery disease. PMID- 11764786 TI - Folate reduces homocysteine levels and lowers rate of restenosis. PMID- 11764787 TI - National hormone & peptide program: peptide hormones (recombinant & natural), hypothalamic peptides, hormones-antisera, other reagents & hormone assay services available. PMID- 11764789 TI - The pros and cons of nuclear fuel recycling. PMID- 11764788 TI - A late Triassic trove of fossil plants. PMID- 11764790 TI - Carbon sinks and conserving biodiversity. PMID- 11764791 TI - Nomenclature for ion channel subunits. PMID- 11764792 TI - [Dean Jean-Pierre Kerneis (1918-1999)]. PMID- 11764793 TI - [The first anti-cancer center in Lyon (1923): surgeon Leon Berard and Auguste Lumiere]. AB - At present, little is known about the creation of cancer hospitals. I will report on that of Lyons, France, with the famous surgeon, Leon Berard (1870-1956). A specialist of neck surgery, he was the first to carry out major thoracoplasties. The cancer hospital was inaugurated in 1923 under the Great Dome of the hotel Dieu hospital. (The dome is the creation of the famous architect Germain Soufflot (1748)). In 1933, the cancer hospital moved in the newly-built Edouard Herriot Hospital; it became independent in 1958, two years after the famous surgeon's death, and it was rightly named after him: "Centre anticancereux Leon Berard". Its creation and its quick development owes a lot to generosity of Auguste Lumiere, one of the two inventors of cinematograph. Auguste Lumiere sponsored radiotherapy material and, at Leon Berard's request (as there was a lack of space in Edouard Herriot hospital), created a centre for cancer patients (Bon Abr Hospital, rue Mistral, with Dr Vigne). A Lumiere gave his time as well as his money for the centre; he was the car-driver, he helped L. Berard with his university classes, and he often comforted the patients while running a private clinic (La Clinique Lumiere), which combined dispensary services with research. (Micheline Bonin) PMID- 11764794 TI - [Vicq d'Azyr and the French Revolution]. AB - Born in April 23th, 1748, at Valognes, in Normandy, Felix Vicq d'Azyr was at once a great doctor, a talented naturalist and a distinguished man of letters. Member of the "Academie des sciences" in 1774, he founded, in 1776, the "Societe royale de medecine" in Paris, future "Academie", whose he was the permanent secretary. He is the originator of the comparative anatomy. The successor to Buffon at the "Academie francaise" in 1788, he became Principal Doctor to the Queen Marie Antoinette in 1789. From that time, his aristocratic tendencies drew revolutionary court's attention to him. Already sick, summary executions of his friends terrified him. He escaped Guillotine, but tuberculosis killed him, on June the 20th, 1794. He left a great work, especially in anatomy and physiology, and a lot of historical eulogies. PMID- 11764795 TI - [A section of divisional stretcher-bearers in 1914-1918 history]. AB - The study of the diary written by the Chief Medical Officer of the French Infantry 34th Division's stretcher-bearers kept in the Chateau de Vincennes historical records as well as the personal documentation he bequeathed enable us to answer to the question: Did the planning of the Military Medical Service induced impediment to wounded men's fast evacuation to rear hospitals? The horrifying overcrowding and, time to time, precarious or inadequate materials led to a flop. But, the study shows that, from year to year, the performance accelerated, then increasing most chances to survive for wounded. PMID- 11764796 TI - [Ambroise Pare, his death and his historians]. AB - Ambroise Pare died December the 20th., 1590. What happened after his death and what are we knowing about his life? Never forgotten, though a lack of care, we were waiting till the XIXth. century to get recollection upon a subject sustained only by accounts of his travels. After Percy, a surgeon who tried to write Pare's biography through the "Biographie universelle ancienne et moderne, de Michaud (1822)" and some second rank authors, Malgaigne is the first who inside a printing of the "Oeuvres completes de Pare (1840-41)" has a fine look upon the question, though his work is incomplete and allows many mistakes. Doctors Chereau and Jal, an historian, analysing civil status records, gave new information enlarged by doctors Le Paulmier, Turner and the U.S. native Janet Doe. PMID- 11764797 TI - [Teyssier before the Supreme Court in January 28, 1942]. AB - Confirming the judgement of the Appeals Court of Bordeaux in 1937, the judgement of the Supreme Court in the case of Teyssier confirmed the duty of the doctor to inform the patient in order to obtain his informed consent. Such information was considered as necessary to respect the person and the rights of the patient. PMID- 11764798 TI - [Lyautey and medicine]. AB - Medicine played a main role during Lyautey own life. He had recourse to it at many times when he was a young boy and suffering of a lot of bad illness all along his life, chiefly in Africa. Maybe it's the reason which allows the strong interest of Lyautey for medicine and doctors? Then medicine is also, according to Lyautey's mind, the most means for conquest and pacification. He proceeded on that way, especially in Marocco which became, owing to him, a modern and peaceful kingdom. PMID- 11764799 TI - [Augustin Belloste (1654-1730), aspects of the surgery in military hospitals during the Piemont-Savoie War (1686-96)]. AB - The surgical practice in military hospitals during the XVIIth century remains poorly known. An original statement is provided by A. Belloste (1654-1730) who enlisted as military surgeon in 1686. In 1690 began the Piemont-Savoie War during which he was in position in the military hospitals of Briancon, Pignerol, and Oulx. In 1696, after the end of the war, A. Belloste published a treatise, the hospital surgeon, written according to the experience he gained and the observations he consigned during his ten years of practice, particularly in the military hospital of Briancon. Interesting information is given concerning the military hospitals recruitment and the patients origins. The transfer to a military hospital seemed to be considered as the last resort, with sometimes wounded persons waiting during long months in dreadful conditions. The pathologies observed and treated consisted principally in war traumatisms by sword or firearms, but also came victims of traumatisms happened during great defensive works as those of Vauban, or presenting pathologies related to the specificites of the alpine environment as falls, altitude or cold... The lodging conditions in hospital were summary, and were often unfavourable to a good evolution of the injuries. A. Belloste particularly developed and defended the interest of a soft, measured, and rational treatment of the wounds. PMID- 11764801 TI - The medical doctor should respond as a conscientious objector to legislation in favour of the crimes of abortion and euthanasia. PMID- 11764800 TI - [Mission to Berlin 1946]. AB - An interallied military delegation went to Spandau, a Berlin suburb, in order to realize the health state of some main Nazis accused of crimes against mankind and waiting to appear before the Nurnberg Court of Justice. PMID- 11764802 TI - The identity of the Catholic medical doctor. PMID- 11764803 TI - The identity of the Catholic nurse. PMID- 11764804 TI - The identity of the Catholic pharmacist on the threshold of the third millennium. PMID- 11764805 TI - The challenges for pharmacists during the third millennium. PMID- 11764806 TI - Teshuvah on assisted suicide. PMID- 11764807 TI - The Court of Appeal and conjoined twins: condemning the unworthy life? AB - The recent decision of the Court of Appeal authorising separation of the conjoined twins 'J' and 'M' appears susceptible to attack on the basis of various inconsistencies. Most fundamentally, the leading judgment of Ward LJ in Re A (Children) (2000) appears to involve a relative devaluation of M's life in consequentialist terms. One life is better than no life appears to be the message, an evaluation apparently reached by reference to 'Quality' of life considerations. But in his speech Ward LJ explicitly rejects such an approach. PMID- 11764808 TI - Can the "quality of life" be used as a criterion in health care services? AB - Because the resources in health care services are limited, different criteria have been used to choose patients for treatment or for non-treatment. The 'Quality of Life' criterion is the one most commonly used in different parts of the world. However the usefulness and necessity of quality of life judgements in health services has always been controversial. This article discusses the 'Quality of Life' criterion from different perspectives. It appears from the discussion that it is not easy to define 'Quality of Life' and the difficulty originates from the relativity of the concept. The article also examines the QALY (Quality Adjusted Life Year), and concludes that it not only involves ageism and sexism but also injustice and unfair discrimination. The article finally argues that it is not possible to measure the quality of life of an individual either accurately or reliably. Therefore it cannot be used as a criterion in health care services. PMID- 11764809 TI - RECs: a response to the articles of Nazi doctors? PMID- 11764810 TI - False promises for European space science. PMID- 11764811 TI - Biotech gap between North and South. PMID- 11764812 TI - Commercial nature of corn germ plasm. PMID- 11764813 TI - The broad reach of helminthology. PMID- 11764814 TI - Implications of the BBA for rural hospitals. PMID- 11764815 TI - Implementation of the State Children's Health Insurance Program in rural areas. PMID- 11764817 TI - Rural home health agencies: the impact of the Balanced Budget Act. PMID- 11764816 TI - Rural and urban patterns of home health use: implications for access under the interim payment system. PMID- 11764818 TI - Medicare reforms: the rural perspective. PMID- 11764819 TI - Potential supply-side implications of the BBA limits on reimbursement to provider based rural health clinics. PMID- 11764820 TI - Data sources to study uncompensated care provided by hospitals. PMID- 11764821 TI - Is the rural safety net at risk? Analysis of charity care provided by rural hospitals in five states. PMID- 11764822 TI - Establishing a fair Medicare reimbursement for low-volume rural ambulance providers. PMID- 11764823 TI - Effect of operator variability on dentin bond strength of two-step bonding systems. AB - PURPOSE: To examine the influence of operator variability on adhesion to dentin of recently developed two-step bonding systems. MATERIALS AND METHODS: A self etching primer system, Fluoro Bond/Lite-Fil II A (FB) and a one-bottle adhesive system, Single Bond/Z100 (SB) were employed. Three groups, each consisting of 15 operators, were selected from the dentists at the university (Group 1), undergraduate students (Group 2), and general practitioners (Group 3). Labial surfaces of extracted bovine teeth were ground on wet 600-grit SiC paper and then washed and dried with oil-free compressed air. These surfaces were treated according to each adhesive system's instructions and the restorative resins were condensed into a Teflon mold (2 mm height, 4 mm internal diameter) and then light cured. The finished specimens were stored in 37 degrees C distilled water for 1 hr. These specimens were tested in a shear mode at a cross-head speed of 1.0 mm/min. The mean and standard deviation were subjected to two-way ANOVA (P < 0.05). RESULTS: Significant differences in bond strength of the two adhesives were found within each operator group. A wider variation in bond strength was seen for SB compared to FB for the three different groups. Mean bond strengths for the faculty group were statistically greater than those of the other two groups, which did not differ significantly. Even though the specimen preparation was done under in vitro conditions, the large coefficients of variation indicate it may be difficult to create suitable surface conditions for optimal bonding. PMID- 11764824 TI - Key concepts of infection control. PMID- 11764825 TI - Caliber-persistent labial artery of the maxillary lip. PMID- 11764826 TI - A randomized, clinical evaluation of the safety and efficacy of a novel oral irrigator. AB - PURPOSE: To evaluate the safety and efficacy of the Braun Oral-B OxyJet (MD15) Oral Irrigator when used as an adjunct to manual brushing. MATERIALS AND METHODS: 64 subjects with mild-to-moderate gingivitis entered this randomized, parallel group, examiner-blind 8-week study. Subjects were assigned to use either the MD15 and a manual brush, or a manual brush alone. Both groups brushed twice daily; the MD15 subjects, in addition to brushing, also used the irrigator in the evening. Subjects were scored at baseline, week 4 and week 8 at up to 168 oral sites for gingival inflammation (modified gingival index), gingival bleeding (angular bleeding index), and plaque (modified plaque index). RESULTS: No adverse events related to study treatment were reported. Use of the MD15 in conjunction with manual brushing resulted in significant (P < 0.05) decreases from baseline in the plaque index at week 8, the gingival index at week 4, and the bleeding index at weeks 4 and 8. The gingival index was also decreased from baseline at week 8, but this was not statistically significant (P = 0.069). The control group also showed significant decreases from baseline for the gingival index at week 8 and the bleeding index at weeks 4 and 8, but plaque scores were not significantly reduced. Although use of the MD15 plus brushing significantly reduced plaque levels from baseline, while brushing alone did not, the difference between the two groups did not achieve statistical significance (P = 0.065). Differences between the groups with respect to the gingival and bleeding indices were also not statistically significant. It is concluded that use of the OxyJet Oral Irrigator in conjunction with manual brushing is safe, reduces plaque and improves gingival health. PMID- 11764827 TI - Microtensile bond strength to dentin and cavity adaptation of Cerec 2 inlay restoration. AB - PURPOSE: To examine the bond strength of Cerec 2 inlays both to dentin surface by microtensile testing and to cavity walls by cavity adaptation in Class II restorations, using three luting materials. MATERIAL AND METHODS: VitaMark II disc was bonded to the coronal dentin surface with Clapearl DC (Clearfil DC)/Linerbond IIsigma (Linerbond 2V), AP-X/Linerbond IIsigma or Fluorocement (Panavia F)/ED Primer. After 24-hr storage in water, microtensile bond strengths (MTB) were measured. Additionally, Cerec inlays were luted to the MO cavities prepared in molars with the same materials. After thermocycling (x2000), the restorations were sectioned mesio-distally. Gap formation was microscopically examined along the cavity walls. RESULTS: There was no significant difference in MTB among the materials (Clapearl DC: 20.89 +/- 4.58 MPa, AP-X: 24.22 +/- 5.97 MPa, Fluorocement: 19.82 +/- 6.43 MPa, Scheffe, P > 0.05). The frequency of gap formation was higher in AP-X than in Clapearl DC and Fluorocement (chi2-test, P < 0.05). Debonding occurred more often at the luting material/dentin interface than at the inlay/luting material interface (Sign test, P < 0.05). PMID- 11764828 TI - Etching effect of 17% EDTA and a non-rinse conditioner (NRC) on primary enamel and dentin. AB - PURPOSE: To investigate the effect of a new non-rinse conditioner (NRC) and 17% EDTA as etchants on the micromorphology of primary tooth enamel and dentin, in comparison with 36% phosphoric acid (PA) when applied for 15 s and 7 s. MATERIALS AND METHODS: Enamel specimens obtained from 40 extracted primary second molars were used to create four groups (n=10) which received the following treatments on unground enamel surface: Group 1: 36% PA/15 s, Group 2: 36% PA/7 s, Group 3: NRC 20 s, Group 4: 17% EDTA/60 s. The same treatments were applied on flattened primary tooth dentin specimens (four groups/n=10). All treated surfaces were examined by SEM. RESULTS: For enamel specimens, a Type II etching pattern was evident in Groups 1 and 3. In Group 2, an uneven Type II pattern was present with prism peripheries partially intact. A mixture of Type II and Type III etching patterns were observed in Group 4. Although all conditioners removed dentin smear to varying degrees, the overall performance of 17% EDTA was weaker than PA and NRC. PMID- 11764829 TI - Stress reduction in resin-based composites cured with a two-step light-curing unit. AB - PURPOSE: To examine the stress reduction of different resin-based composites, cured with a two-step polymerization unit (Elipar Highlight) by means of a photoelastic investigation. MATERIALS AND METHODS: For each material (Pertac II, Tetric Ceram, Charisma F, Solitaire, Dyract, Dyract AP, Definite), a minimum of 10 resin samples, embedded in acrylic-glass plates, were polymerized using a standard polymerization process of 700 mW/cm for 40 s. Another 10 samples were polymerized with a light output of 150 mW/cm2 for 10 s and then with a light output of 700 mW/cm2 for 30 s. RESULTS: For Pertac II the reduction of polymerization stress in the two-step-mode was 15.5%, for Tetric Ceram 14.5%, for Solitaire 8.1%, for Dyract AP 6.5% and for Definite 4.7%. These differences in polymerization stress between the standard and two-step-polymerization mode were statistically significant (P < 0.01, Wilcoxon test). No statistically significant differences in polymerization stress could be found for Charisma F and Dyract. PMID- 11764830 TI - Tensile bond strength of filled and unfilled adhesives to dentin. AB - PURPOSE: To determine the tensile bond strength of three filled and two unfilled adhesives applied to bovine dentin. MATERIALS AND METHODS: Fragments of the labial dentin of bovine incisors were embedded in PVC cylinders with self-cure acrylic resin, and ground flat using 200 grit and 600 grit sandpaper. The following adhesive systems were tested (n=10): Prime & Bond NT, Prime & Bond NT dual cure, Prime & Bond 2.1, OptiBond Solo and Single Bond. A 3 mm-diameter bonding surface was delimited using a perforated adhesive tape. After etching with 37% phosphoric acid and adhesive application, a resin-based composite truncated cone (TPH, shade A3) was built. Tensile test was performed after 24 hrs storage in distilled water at 37 degrees C. Failure mode was accessed using a x10 magnification stereomicroscope. RESULTS: Weibull statistical analysis revealed significant differences in the characteristic strength between Single Bond and Prime & Bond NT dual cure, and between Single Bond and Prime & Bond 2.1. The Weibull parameter (m) was statistically similar among the five groups. Single Bond and Prime & Bond NT showed areas of dentin cohesive failure in most of the specimens. For OptiBond Solo, Prime & Bond NT dual cure and Prime & Bond 2.1 failure was predominantly adhesive. PMID- 11764831 TI - Marginal integrity after fatigue loading of ceramic inlay restorations luted with three different cements. AB - PURPOSE: To evaluate the effect of fatigue loading on the quality of the cement around the margins of adhesive ceramic MOD inlays. MATERIALS AND METHODS: Non metal IPS Corum porcelain inlays were made and cemented either with the resin based composite Variolink, the compomer Dyract-Cem or the glass-ionomer cement Ketac-Cem. For each system, half of the specimens were subjected to thermal and mechanical load cycling to simulate fatigue loading. All teeth were then sectioned and evaluated by SEM on topography and by optical microscopy for dye penetration. RESULTS: Before loading, all systems showed good marginal integrity. After loading, inlays cemented with Variolink and Dyract-Cem showed no significant (P > 0.05) increase in marginal break down, however restorations cemented with Ketac-Cem, showed a significant (P < 0.05) deterioration at the margins. PMID- 11764832 TI - Pulp response to direct capping with an adhesive system. AB - PURPOSE: To evaluate the pulp response following direct pulp capping with an adhesive system (Prime & Bond 2.0 - PB 2.0) and a zinc-oxide eugenol cement (ZOE) on pulp exposures in rat molar teeth. MATERIALS AND METHODS: Forty-eight Class I cavities were prepared on the occlusal surface of molar teeth of rats (Rattus Norvegicus, Holtzman). Pulp exposures performed on the cavity floor were capped either with the adhesive system P&B 2.0 or ZOE. After 7, 15, 30, and 60 days, the specimens were processed through H & E and Brown & Brenn staining techniques. RESULTS: Both pulp capping materials allowed pulp repair, characterized by reorganization of a new odontoblast cell layer underlying the dentin bridge formation. However, P&B 2.0 promoted a large zone of cell-rich fibrodentin matrix deposition between the pulp capping material and the dentin bridge, which was deposited far from the pulp exposure site. On the other hand, pulps capped with ZOE showed dentin bridging immediately subjacent to the pulp capping material. In those samples in which microleakage occurred between dental material and cavity walls there was a persistent inflammatory reaction and lack of complete pulp repair. PMID- 11764834 TI - Marginal leakage of filled dentin adhesives used with wet and dry bonding techniques. AB - PURPOSE: To evaluate the effect of wet and dry bonding on microleakage of Class V restorations bonded with three filled bonding agents. MATERIALS AND METHODS: Sixty extracted human premolar and molar teeth were randomly assigned to five groups for bonding with OptiBond Solo, PermaQuick PQI, Prime & Bond NT (one coat), Prime & Bond NT (two coats) and Prime & Bond 2.1, as a control material. Cavities were cut in both the buccal and lingual surfaces. Half of each preparation was in enamel and the other was in cementum/dentin. The cavities were restored with resin-based composite after the application of dentin bonding agents using a wet and dry technique for each material. The teeth were stored in distilled water for 6 days at 37 degrees C, thermocycled, and the restorations examined microscopically for leakage using Procion Brilliant Red as a marker. RESULTS: All groups showed microleakage at both the enamel and dentin margins. At the gingival margin, there was a significant difference between the groups for wet bonding (P = 0.0349) but not for dry bonding (P = 0.9983) (Kruskal-Wallis test). There was no significant difference between the groups at the enamel margin (wet bonding: P = 0.9999, dry-bonding: P = 0.9304) (Kruskal-Wallis test). The wet-bonding technique was compared with the dry-bonding technique for each material at both the gingival and enamel margins and no significant differences were observed (in all cases P > 0.5) (Mann-Whitney U-test). PMID- 11764833 TI - Effect of conditioner and restorative resin on enamel bond strengths. AB - PURPOSE: To evaluate the effect of three enamel conditioners and four restorative materials on enamel shear bond strengths. MATERIALS AND METHODS: 120 bovine incisors were polished to 600-grit and randomly assigned to three enamel adhesive systems (n=40): Syntac Single Component with phosphoric acid etching (PA-SSC), Syntac Single Component without phosphoric acid etching (SSC), and Experimental Prompt L-Pop (LPI), a self-etching adhesive. The specimens were restored with one of four resin restorative materials (n=10): (1) Compoglass F, a high-viscosity compomer; (2) Compoglass Flow, a low-viscosity compomer; (3) Tetric Ceram, a high viscosity resin-based composite (RBC); and (4) Tetric Flow, a low-viscosity RBC. After thermocycling, shear tests were carried out with an Instron Universal Testing Machine. Mean enamel bond strengths were analyzed with ANOVA and Duncan post hoc test at P < or = 0.05. RESULTS: PA-SSC resulted in higher mean bond strengths than LP1, but the difference was not statistically significant. Both PA SSC and LP1 resulted in statistically higher mean bond strengths than SSC at P < or = 0.0001. The lowest mean bond strengths of all the groups were obtained when SSC was used with an RBC (Tetric Ceram or Tetric Flow). SSC and PA-SSC resulted in statistically higher mean bond strengths when used with a compomer than when used with an RBC, regardless of the viscosity. Although recommended to be used only with compomers, LP1 resulted in statistically similar enamel bond strengths when used with the composite of corresponding viscosity (Tetric Ceram vs. Compoglass F; Tetric Flow vs. Compoglass Flow). LP1, however, resulted in higher enamel bond strengths when combined with Tetric Ceram than when combined with Tetric Flow. When the results were pooled for "viscosity", high-viscosity restorative materials resulted in higher bond strengths than low-viscosity materials at P < or = 0.041. When the data were pooled for "restorative material", compomers resulted in higher bond strengths than composites at P < or = 0.0001. PMID- 11764836 TI - Scalar timing without reference memory? Episodic temporal generalization and bisection in humans. AB - Three experiments tested whether the scalar property of timing could occur when humans timed short durations under conditions in which it was unlikely that they developed reference memories of temporal "standards". Experiment 1 used an episodic version of a temporal generalization task where judgements were made of the potential equality of two durations presented on each trial. Unknown to the subject, one of these was always 200, 400, 600, or 800 ms, and the other was of variable duration. Temporal generalization gradients showed the scalar property of superimposition at standard values greater than 200 ms. Experiment 2 used a variant of the "roving bisection" method invented by Rodriguez-Girones and Kacelnik (1998) modified so that the scalar property of timing could be observed empirically. Data from bisection with short/long standard pairs of 100/400, 200/800, and 300/1,200 ms showed nearly perfect scalar-type superimposition. Experiment 3 again used episodic temporal generalization, but durations were never repeated and came from three distinct time ranges. Superimposition was found across these ranges except for the shortest visual stimuli timed. The data suggested that scalar timing could occur in humans in conditions where the formation of reference memories of temporal standards was highly improbable. PMID- 11764835 TI - Fracture strength of fragment-bonded teeth. Effect of calcium hydroxide lining before bonding. AB - PURPOSE: To measure, in vitro the strength of intact teeth, fracture-bonded teeth, and fracture-bonded teeth bonded after a preliminary calcium hydroxide lining of the dentin part of the remaining tooth. MATERIALS AND METHODS: The study used 30 young, similarly aged sheep incisors. Twenty incisors were fractured 2.5 mm from the incisal edge and another 10 incisors remained non fractured and served as control (Group 1). Group 2 comprised 10 fractured incisors, which after 3 weeks water storage were bonded by use of acid etching and a dentin bonding agent. In Group 3, the root part of 10 fractured incisors were lined with calcium hydroxide and kept in water for 3 weeks. Then the lining was removed with a hand instrument before bonding as above. The strength of the teeth in Groups 1-3 was measured and the mean fracture strengths representing the three groups were compared by Newman-Keuls' multiple range tests at a 5% level of significance. RESULTS: The mean fracture strength of the lined teeth (9.6 MPa) was significantly different from that of intact teeth (17.8 MPa) as well as from that of the bonded but unlined teeth (15.8 MPa). The latter two means were not significantly different. It is concluded that the use of calcium hydroxide on the fracture surfaces of fractured teeth before bonding lowers the fracture strength of the restored teeth. PMID- 11764837 TI - Retrospective revaluation in humans: learning or memory? AB - The phenomenon of retrospective revaluation has posed considerable problems for many associative learning theories as it involves a change in the associative strength of a cue on trials on which that cue is absent. The present series of experiments pursues this idea of changes in associative strength between evoked representations of cues, in an effort to establish, de novo, an excitatory connection between two cues simultaneously activated in memory. Given the finding of Dwyer, Mackintosh, and Boakes (1998) that simultaneous activation of absent cues in the memory of rats resulted in learning comparable to that seen in retrospective revaluation, we expected that if retrospective revaluation was found in humans, then excitatory learning due to simultaneous activation would also be seen. This was not the case. The implications of our results are discussed in terms of Dickinson and Burke's (1996) modified SOP model and a version of McLaren's (1993) APECS network. We conclude that many of the effects attributed to learning in retrospective revaluation studies are better thought of as due to changes in the retrievability of items in memory. PMID- 11764838 TI - The effects of pre-exposure on escape from a Morris pool. AB - In two experiments rats were pre-exposed to the landmarks surrounding a Morris pool while they swam to a platform with a beacon attached to it. They were then required to escape from the pool by finding the platform, without the beacon, in a new position. When the platform remained in the same place for each pre exposure session, but was moved from session to session, then subsequent escape from the pool was more rapid than when the landmarks were not visible during pre exposure (Experiment 1). But when the platform was moved from trial to trial during pre-exposure, then subsequent escape from the pool was disrupted (Experiments 1 and 2). It is proposed that pre-exposure to the landmark alters the attention that is paid to them, which then influences how readily the landmarks can be used to identify the new position of the platform. PMID- 11764839 TI - Intermodal blocking in honeybees. AB - Previous findings of intramodal but not of intermodal blocking in foraging honeybees prompted a new series of experiments with colours, odours, a proximal visual landmark, and a localized geomagnetic anomaly as stimuli. In Experiments 1 2, the landmark was blocked by both colour and odour. In Experiments 3-6, the anomaly was blocked by both colour and odour, but the anomaly failed to block either colour or odour. In Experiments 7-8, the anomaly failed again to block either colour or odour even though it could be shown to develop substantial associative strength in the course of the training. The several instances of intermodal blocking bring the results for honeybees into closer agreement than before with the results for vertebrates. The failures of blocking seem understandable in terms of the relative salience of the stimuli employed without reference to modal relationships. An attentional interpretation is suggested. PMID- 11764840 TI - The state of doctoral education in health administration and policy. PMID- 11764841 TI - The future of doctoral education in health administration and policy. AB - Doctoral education in health administration and policy has exhibited stagnation over the past decade in terms of enrollment, graduates, curricula, etc. However, this apparent overall stagnation masks some significant changes that should accelerate in the years ahead. This paper examines the current challenges for doctoral programs in health administration and policy in terms of program orientation, program content, student profiles, and the job market. Given these challenges, predictions are made concerning future enrollment growth in various types of doctoral programs over the next ten years. Finally, recommendations concerning program orientation, program content, student profiles, and the job market are provided overall and by program type. The two most important recommendations that apply across-the-board are to update data on doctoral education and to seek foundation support for a fundamental reassessment of doctoral education for the twenty-first century. PMID- 11764842 TI - Diversity in health administration doctoral education: alternative scenarios for the future. AB - Doctoral programs in health administration are characterized by extreme diversity in focus, format, content, and market. The observed diversity reflects two key structural attributes of health administration as a doctoral field of study: 1) its multidisciplinary base, and 2) its small size. These attributes leave doctoral programs vulnerable to a host of external pressures. The field lacks structure and organizing principles at the national or international level, and students, employers, and other stakeholders suffer some damaging consequences. Pressures from the institutional environment are weak and splintered (among the constituent disciplines of health administration), while the technical environment (economic forces such as competition for students and research funding) produces a powerful set of incentives that shape the form and substance of health administration doctoral education. As alternatives to the current hybrid nature of the field, two additional future scenarios are considered: Integration with Health Services Research, and Integration with Business Administration. The future of health administration doctoral education is interdependent with 1) the continued differentiation of health administration as a master's field of study; 2) trends in research funding; and 3) economies in the delivery of small-scale or individually customized doctoral education. At the least, programs and students currently would benefit from more information classifying program breadth and goals and reporting outcomes; more adequate information on careers and placement; and a modicum of workforce planning. PMID- 11764843 TI - The Doctor of Health Administration: an educational innovation for healthcare executives. AB - This article describes the development and implementation of an innovative doctoral program designed to enhance the knowledge and skills of healthcare executives. The program is a Doctor of Health Administration (D.H.A.) Degree with a specific focus on leadership. This sets the program at the Medical University of South Carolina apart from all others in being the first D.H.A. offered in the United States and the only program at the time to place its primary emphasis on leadership. PMID- 11764844 TI - Doctoral education in executive format, or fitting the Procrustean Bed: an exercise in organizational change. AB - Doctoral education in health administration has been heavily influenced by the model of the traditional academic research Doctor of Philosophy. This powerful traditional template has been appropriate for the advancement of research and scholarship in health systems administration, but not necessarily for the advancement of the field of practice. With the advent of executive doctoral programs that feature larger student cohorts, routinized curricula, and student bodies comprised of experienced professionals, the expectations for doctoral study in health systems administration are being tested as new models evolve. Faculty are reluctant to depart from the traditional doctoral forum, but will do so based upon demonstrated advantages in the area of publication opportunities, student responsiveness, and financial inducements. This paper examines the program in an executive format conforming to the existing degree offerings of the School of Public Health, and the process of balancing the traditional academic expectations with the executive format of content delivery. PMID- 11764845 TI - An integrated doctoral educational model for developing researchers in health care strategic management. AB - Doctoral education varies according to how students that graduate from a particular program are prepared for various type of careers. PhD programs principally work to develop researchers; researchers produce and disseminate new knowledge in a given area of expertise. This manuscript looks specifically at a PhD program designed to produce researchers in healthcare strategic management. This program is based in a business school and builds on general business principles to produce strategists that do research in the healthcare context. The business school program (type B) will be analyzed according to the areas (or potential areas) of research done by its graduates. The different areas are shown in a table where one axis is research content (i.e., specifically what the functional area of research is) and the other axis is publication outlet (i.e., what journal the research is disseminated in). Advantages of the type B program are compared to advantages of a PhD program based in a healthcare administration or healthcare management school (type H program) in terms of publications in these different areas. PMID- 11764846 TI - The Kentucky plan: an innovative approach to professional doctoral education in public health. AB - The Doctor of Public Health (Dr.P.H.) degree is designed to prepare graduates for the highest levels of leadership in public health related careers in both public and private settings. The Kentucky School of Public Health has developed an innovative generalist professional degree program offering an extensive battery of courses based on the body of professional public health knowledge. The degree includes extensive supervised field experience as part of the academic training, linking theory with practice. Issues related to professional degrees, curriculum, accreditation and certification, admission, evaluation, plans for institutional cooperation, and demand are addressed. PMID- 11764847 TI - Effects of metals on the nervous system of humans and animals. AB - Several metals have toxic actions on nerve cells and neurobehavorial functioning. These toxic actions can be expressed either as developmental effects or as an increased risk of neurodegenerative diseases in old age. The major metals causing neurobehavioral effects after developmental exposure are lead and methylmercury. Lead exposure in young children results in a permanent loss of IQ of approximately 5 to 7 IQ points, and also results in a shortened attention span and expression of anti-social behaviors. There is a critical time period (<2 years of age) for development of these effects, after which the effects do not appear to be reversible even if blood lead levels are lowered with chelation. Methylmercury has also been found to have effects on cognition at low doses, and prenatal exposure at higher levels can disrupt brain development. Metals have also been implicated in neurodegenerative diseases, although it is unlikely that they are the sole cause for any of them. Elevated aluminum levels in blood, usually resulting from kidney dialysis at home with well water containing high aluminum, result in dementia that is similar to but probably different from that of Alzheimer's disease. However, there is some epidemiological evidence for elevated risk of Alzheimer's in areas where there is high concentration of aluminum in drinking water. Other metals, especially lead, mercury, manganese and copper, have been implicated in amvotrophic lateral sclerosis and Parkinson's disease. PMID- 11764848 TI - Exposure to lead and male fertility. AB - Lead is a reproductive toxicant. Exposure to inorganic lead is detrimental to human semen quality. The studies of the risk of spontaneous abortion and congenital malformation have shown contradictory findings. The aim of the following review is to summarise the epidemiological evidence of the effects of inorganic lead on male fertility. The focus is on epidemiological studies of time to-pregnancy and related fertility measures. Blood lead measurements were applied to exposure assessment in all the studies. The results of the studies on fertility rates are consistent in showing an association between lead and reduced fertility. Also, there seems to be a tendency towards stronger association at older age with increasing duration of exposure. The independent roles of exposure duration and effect modification by age may have been difficult to distinguish. There is a paucity of studies on time taken to conceive. The studies conducted only weakly suggest that male exposure to lead is associated with delayed conception. The findings of time-to-pregnancy and fertility rate studies contradict. The possible reasons for this discrepancy is discussed briefly. There are a number of mechanisms by which exposure to lead may reduce male fertility. On the basis of animal studies, alterations in sperm chromatin stabilitv or epigenetic effects may be the most probable mechanisms involved at low exposure level. PMID- 11764849 TI - Blood concentration of essential trace elements and heavy metals in workers exposed to lead and cadmium. AB - The aim of the study was to determine blood concentration of essential trace elements (Se, Zn, Cu) and toxic metals (Pb, Cd), markers of antioxidant (activities of glutathione peroxidase (GPx), superoxidase dismutase and ceruloplasmin) and prooxidant processes (thiobarbituric acid reactive substances (TBARS)) in workers exposed to Pb and Cd. Forty three male workers of the lead acid batteries department, aged 25-52 years, and twenty two workers, including 15 women, aged 36-51 years, exposed to Cd in the alkaline batteries department were examined. The reference group consisted of 52 healthy inhabitants of the same region. It was found that Se concentration and GPx activity in both erythrocytes and plasma of Cd exposed workers were significantly lower (p < 0.001) than in the reference group. We found an inverse linear correlation between blood Se and Cd concentrations in the workers exposed to Cd (r = -0.449; p < 0.01). Moreover, the activity of erythrocyte and plasma GPx was shown to be significantly lower in the study group of workers (p < 0.001). It was observed that TBARS concentration in plasma was significantly higher (p < 0.05) in the lead exposed workers than in the group without contact with Pb. Our results indicate that exposure to Pb and Cd affects the antioxidant potential of blood in workers exposed to heavy metals. PMID- 11764850 TI - Health risk of urban soils contaminated by heavy metals. AB - The paper presents the results of geochemical investigations carried out in the city of Prague. Czech Republic, between the years 1994-1997, by the Czech Geological Institute, National Institute of Public Health and Hygiene Stations of Prague. Exposure assessment for children as the most sensitive population, based on soil ingestion pathway, indicates that lead is the major pollutant of concern, especially in the central regions of the city. Direct exposure assessment was done by analyzing blood and urine samples collected from children aged 3-6 years. Blood lead levels were the only biomarker significantly higher as compared to the control group (32.1 +/- 17.4 microg/l, 25.1 +/- 15.4 microg/l). This pilot study supports the establishment of a new sub-system within the already existing System of Monitoring the Environmental Impact on Population Health of the Czech Republic. PMID- 11764851 TI - Developing tools for phytoremediation: towards a molecular understanding of plant metal tolerance and accumulation. AB - Certain plant species and genotypes are able to accumulate large quantities of heavy metals in their shoots. Based on this trait the concept of phytoremediation was developed, i.e. the use of metal hyperaccumulating plants for the cleansing of contaminated soils and water. In order to more efficiently use this capacity, an engineering of plants might be needed. However, very little is known about the underlying molecular mechanisms. Our work is focussing on the identification and characterization of plant genes involved in plant metal uptake, tolerance and accumulation. Phytochelatins are small glutathione-derived metal-binding peptides which are part of the plant metal detoxification system. Genes encoding phytochelatin synthases have been cloned and are now being studied with regard to their regulation, biochemistry and biotechnological potential. Another project aimes at the dissection of metal responses in the metallophyte Arabidopsis halleri. This plant, a close relative to the model plant Arabidopsis thaliana, is Cd hypertolerant and Zn hyperaccumulating. It grows, for instance, on medieval mining sites in the Harz mountains in Germany and in many other metal contaminated sites in Central Europe. We have isolated metal-regulated genes from A. halleri and molecularly analyzed interesting candidate genes with regard to their function and involvement in metal accumulation and tolerance. PMID- 11764853 TI - Geochemistry of acid mine contamination-aquifer interactions. AB - The Pinal Creek Basin near Globe, Arizona, is an example of a groundwater/surface water system contaminated by wastes from historic metal mining practices. Acidic mining wastes that have leached into the regional aquifer have come in contact with alluvial sediments, dissolving manganese oxides and precipitating iron sulfato-hydroxides. Manganese is reoxidized in sediments of a perennial stream (Pinal Creek) formed as the aquifer thins and groundwater is forced to land surface. Iron and manganese in the system are inextricably linked through redox couples. These interactions, which produce reaction rates varying by orders of magnitude and non-stoichiometric release of manganese, are poorly understood. We have designed a flow-through reaction cell to obtain in situ real time X-ray adsorption spectroscopy (XAS) data during geochemical reactions. By coupling solution chemistry data with spectroscopic measurements, we were able to show that the spinel mineral, jacobsite, forms as a metastable intermediate phase during the reductive dissolution of manganese oxide (MnO2) by ferrous iron (Fe(II)). The production of Fe(III) followed by the precipitation of ferric hydroxides and the formation of the jacobsite phase, were responsible for reducing the rate of the reaction as time progressed. Laboratory studies have determined that Mn-oxidation in stream sediments increases Co, Ni, and Zn loading through a variety of processes, including oxidation, co-precipitation, solid solution formation, structural exchange, and/or sorption. This information provides a more complete picture of the controls on metal transport and attenuation in the Pinal Creek Basin. PMID- 11764852 TI - Remediation of metal-contaminated soil and sludge using biosurfactant technology. AB - Development of environmentally benign approaches to remediation of metal contaminated soils and sewage sludges are needed to replace currently used techniques of either landfilling or metal extraction using caustic or toxic agents. We report results from four application technologies that use a metal chelating biosurfactant, rhamnolipid, for removal of metals or metal-associated toxicity from metal-contaminated waste. The four applications include: 1) removal of metals from sewage sludge; 2) removal of metals from historically contaminated soils; 3) combined biosurfactant/phytoremediation of metal-contaminated soil; and 4) use of biosurfactant to facilitate biodegradation of the organic component of a metal-organic co-contaminated soil (in this case the biosurfactant reduces metal toxicity). These four technologies are nondestructive options for situations where the final goal is the removal of bioavailable and leachable metal contamination while maintaining a healthy ecosystem. Some of the approaches outlined may require multiple treatments or long treatment times which must be acceptable to site land-use plans and to the stakeholders involved. However, the end-product is a soil, sediment, or sludge available for a broad range of land use applications. PMID- 11764854 TI - Impact of metals on the environment due to technical accident at Aurul Baia Mare, Romania. AB - The S.C. Aurul S.A. is a joint venture company owned by the Esmeralda from Australia and the "Remin" National Company of Precious and Non-ferrous Metals in Romania, established in 1992. The design concept was to transport the mining waste away from the city, while the gold and silver in the tailings could be recovered, using efficient and modern technology that was not available at the time the dam was established. On 30 January, 2000, at 22.00, the dam burst and released 100,000 cubic meters of tailing pulp, heavily contaminated with cyanide and cyanide complexes, especially with copper, into the Lapus and Somes tributaries of the river Tisa. The paper deals with the impact of metals on the environment associated with their presence in surface waters, river sediments and soils. PMID- 11764855 TI - Spatial variability and trends in ambient air concentrations of metals in Cracow, Poland. AB - Even though the air quality has been improving since the beginning of the 1980s, Cracow still belongs to the most polluted cities in Poland. The air pollution originates mainly from industry, small-size emission sources and transport. Metals in ambient air have been monitored since 1992 by 4 stations located within the city. The aim of the study was to determine the city areas where the national limits of heavy metals in suspended particles are exceeded and to assess the trends for the years 1992-1999. The monthly mean and maximum values of lead, zinc, chromium, copper, cadmium, nickel and iron were used in the analysis. Between 1992 and 1999, the level of most monitored metals in suspended particles was much below the national standards. Only the concentration of lead exceeded the limits by 50% in the area with the station monitoring traffic air pollution. However, the substantial variability in concentrations of monitored metals observed within the city was most pronounced around the metallurgical plant. Nowadays a new factor prevails: heavy traffic has resulted in a substantially enhanced concentration of lead across the city. PMID- 11764856 TI - Mortality pattern in the cohort of workers exposed to carbon disulfide. AB - The objective of the study was to assess mortality in the cohort of the viscose factory workers occupationally and environmentally exposed to carbon disulfide. Male workers employed for at least one year during 1950-1985 in the production or maintenance departments, living in the vicinity of the plant, were enrolled into the study. Of the 2,878 workers in the cohort, 2,762 were successfully traced, yielding 76,465 person-years. Mortality assessment was based on the standardized mortality ratio using a person-years method. The general male population of Poland was considered as a reference group. Total mortality in the cohort was higher than in the general male population in Poland (SMR = 108). A significantly increased risk of deaths was observed for all cardiovascular (SMR = 114) and cerebrovascular (SMR = 208) diseases. Analyses showed a significantly elevated risk of death from the circulatory system diseases in the men of the "highly exposed" group, spinners and those who were first employed before 1974. A statistically significant trend of mortality from all cardiovascular diseases in relation to the level of exposure (assessed qualitatively) was evident. No clear relationship between duration of exposure and the risk of death was found. PMID- 11764857 TI - Effects of exposure to tobacco smoke in pregnancies complicted by oligohydramnios and premature rupture of the membranes. II. Activity of brush border enzymes in human amniotic fluid. AB - The aim of the present study was to assess the activity of membrane enzymes: alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT) and trehalase in amniotic fluid of women who smoke cigarettes during pregnancy complicated by idiopathic oligohydramnios or premature rupture of the membranes (PROM). The enzyme activity was measured between 22 and 31 (group A) and between 32 and 39 (group B) weeks of gestation. In the women of group A with idiopathic oligohydramnios, AAP activity was five times higher than in PROM women. AAP activity was declining with the progression of gestation, and in the B group women with oligohydramnios, it was over eight times lower than in group A. A threefold increase in GGT activity was found in women of group A with oligohydramnios as compared to women of group A with PROM. No statistically significant differences in trehalase activity were found in amniotic fluid of women with oligohydramnios and PROM, AAP, GGT and trehalase activity in women with idiopathic oligohydramnios correlated with the cadmium ion concentration, and AAP and GGT activity with the lead ion concentration in amniotic fluid which confirms toxical properties of these heavy metals present in cigarette smoke. It has already been confirmed that measurements of the brush border enzyme activity in amniotic fluid are very useful in prenatal diagnosis and detection of the placenta disorders. PMID- 11764858 TI - UV radiation emitted by selected sources at work stands. AB - The paper presents the results of UV effective irradiance measurements at work stands for sources such as: welding arcs, gas blowpipes, exposure processes, printing machines and insecticide lamps. The irradiance measurements were performed using broad-band instruments with detector heads corrected to the Polish action spectra (erythematous and conjunctivitis). The obtained values of effective irradiance for the above sources ranged from 0.2 to 8,000 mW/m2. Safe exposure time corresponding to irradiance was calculated for the Polish threshold limit values. For welding processes the spectra of selected welding arcs are presented additionally. These spectra were measured using a fiber-optic spectrometer. PMID- 11764859 TI - Polish bibliography of occupational medicine, 2000. Part 1. PMID- 11764860 TI - Verrucous carcinoma. PMID- 11764861 TI - Combination therapy for type 2 diabetes. PMID- 11764862 TI - Work-related asthma. AB - Work-related asthma accounts for at least 10 percent of all cases of adult asthma. Work-related asthma includes work aggravation of preexisting asthma and new-onset asthma induced by occupational exposure. Occupational exposure to very high concentrations of an irritant substance can produce reactive airway dysfunction syndrome, while exposure to allergenic substances can result in allergic occupational asthma. An important step in the diagnosis of work-related asthma is recognition by the physician of the work relatedness of the illness. A thorough history can elucidate the work relation and etiology. Objective tests, including pulmonary function, nonspecific and specific bronchial hyperresponsiveness, serial peak expiratory flow rates, and skin allergies, should be performed to confirm the diagnosis of asthma and demonstrate a work correlation. Treatment for occupational asthma--use of anti-inflammatory medications such as inhaled steroids and bronchodilators--is the same as that for nonoccupational asthma. Prevention is an integral part of good medical management. In patients with work-aggravated or irritant-induced asthma, reduction of exposure to aggravating factors is essential. In patients with allergic occupational asthma, exposure should be eliminated because exposure to even minute concentrations of the offending agent can trigger a potentially fatal allergic reaction. PMID- 11764863 TI - Gastroesophageal reflux in infants and children. AB - Gastroesophageal reflux is a common, self-limited process in infants that usually resolves by six to 12 months of age. Effective, conservative management involves thickened feedings, positional treatment, and parental reassurance. Gastroesophageal reflux disease (GERD) is a less common, more serious pathologic process that usually warrants medical management and diagnostic evaluation. Differential diagnosis includes upper gastrointestinal tract disorders; cow's milk allergy; and metabolic, infectious, renal, and central nervous system diseases. Pharmacologic management of GERD includes a prokinetic agent such as metoclopramide or cisapride and a histamine-receptor type 2 antagonist such as cimetidine or ranitidine when esophagitis is suspected. Although recent studies have supported the cautious use of cisapride in childhood GERD, the drug is currently not routinely available in the United States. PMID- 11764864 TI - Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. AB - The steady increase in resistant organisms is related to the widespread use of antibiotics in community and hospital settings. New therapeutic options are needed, including treatments for infections caused by antibiotic-resistant gram positive organisms. Quinupristin-dalfopristin, the first formulation of a distinct class of antibiotics known as the streptogramins, has activity against a range of gram-positive bacteria that are usually resistant to other agents, including vancomycin-resistant Enterococcus faecium. The pharmacodynamic (postantibiotic effect) and pharmacokinetic characteristics of quinupristin dalfopristin allow dosing at eight- to 12-hour intervals. The safety profile of the formulation is generally favorable, with no demonstrable ototoxicity, nephrotoxicity, bone marrow suppression, or cardiovascular adverse effects. Reversible arthralgias, myalgias, and peripheral venous irritation are the formulation's major side effects. A potential for drug interactions exists because quinupristin-dalfopristin significantly inhibits the cytochrome P450-3A4 enzyme system. Quinupristin-dalfopristin has been shown to be effective in the management of documented severe infections caused by vancomycin-resistant E. faecium, nosocomial pneumonia, and infections related to the use of intravascular catheters. PMID- 11764865 TI - Psycho dermatology: the mind and skin connection. AB - A psychodermatologic disorder is a condition that involves an interaction between the mind and the skin. Psychodermatologic disorders fall into three categories: psychophysiologic disorders, primary psychiatric disorders and secondary psychiatric disorders. Psychophysiologic disorders (e.g., psoriasis and eczema) are associated with skin problems that are not directly connected to the mind but that react to emotional states, such as stress. Primary psychiatric disorders involve psychiatric conditions that result in self-induced cutaneous manifestations, such as trichotillomania and delusions of parasitosis. Secondary psychiatric disorders are associated with disfiguring skin disorders. The disfigurement results in psychologic problems, such as decreased self-esteem, depression or social phobia. Most psychodermatologic disorders can be treated with anxiety-decreasing techniques or, in extreme cases, psychotropic medications. PMID- 11764866 TI - Counseling for tobacco cessation. PMID- 11764867 TI - Photo quiz. Chronic ulcerated lesion on the face. PMID- 11764868 TI - CDC updates interim guidelines for anthrax exposure management and antimicrobial therapy. PMID- 11764869 TI - Duplicate or fraudulent publications. PMID- 11764870 TI - Soft-tissue images. Malignant degeneration of heterotopic pancreas. PMID- 11764871 TI - Soft-tissue case 42. Hypothenar hammer syndrome. PMID- 11764872 TI - Musculoskeletal case 19. Giant cell tumour of the tibia. PMID- 11764873 TI - Recognition and management of atlanto-occipital dislocation: improving survival from an often fatal condition. AB - OBJECTIVE: To provide an overview of atlanto-occipital dislocation and associated occipital condyle fracturcs so as to alert physicians to this rare injury and potentially improve patient outcome. The pertinent anatomy, mechanism of injury, clinical and radiologic evaluation and the management of these rare injuries are discussed in an attempt to alert physicians to this type of injury and to improve outcome. DATA SOURCES: The data were obtained from a MEDLINE search of the English literature from 1966 to 1999 and the experience of 4 spine surgeons at a quaternary care acute spinal cord injury unit. STUDY SELECTION: Detailed anatomic and epidemiologically sound radiology studies were identified and analyzed. Only small retrospective studies or case series were available in the literature. DATA EXTRACTION: Valid anatomic, biomechanical and radiologic evaluation was extracted from studies. Clinical data came from limited studies and expert opinion. DATA SYNTHESIS: Early diagnosis is essential and is facilitated by a detailed clinical examination and strict adherence to an imaging algorithm that includes CT and MRI scanning. When the dislocation is identified, timely gentle reduction and prompt stabilization throuigh nonoperative or operative means is found to optimize patient outcome. CONCLUSIONS: Atlanto-occipital dislocation should be suspected in any patient involved in a high speed motor vehicle or pedestrian collision. Once suspected, proper imaging and appropriate management of these once fatal injuries can improve survival and neurologic outcome. PMID- 11764874 TI - Standard anatomical medullary locking (AML) versus tricalcium phosphate-coated AML femoral prostheses. AB - OBJECTIVES: To compare the preliminary rate and amount of bony ingrowth and calcar resorption between patients receiving either a standard anatomical medullary locking (AML) or a tricalcium phosphate (TCP)-coated AML femoral prosthesis and to compare preliminary clinical results. DESIGN: A prospective, randomized, double-blind clinical trial. SETTING: An acute care tertiary institution. PATIENTS: Between January 1993 and March 1995, 92 patients underwent primary total hip arthroplasty (THA). They were randomized to 2 groups of 46--a control group or a treatment group. Of the 46 subjects enrolled in each group, no significant differences were seen preoperatively with respect to age, sex, diagnosis, clinical and radiographic assessment. Seventy-one patients were followed up for 24 months. INTERVENTIONS: Insertion of either a standard AML femoral implant (control group) or a TCP-coated AML femoral implant (treatment group). OUTCOME MEASURES: The degree of hypertrophy, calcar atrophy and the number of spot welds on standard postoperative radiographs at 6, 12 and 24 months. Clinically, assessment according to the Societe internationale de chirurgie orthopedique et de traumatologie (SICOT) scale and a 100-point visual analogue scale (VAS) for pain. RESULTS: There were no prosthetic stem revisions in either group at the 24-month follow-up. Radiographically, bony ingrowth was not significantly different in the TCP-coated stem, by chi2 analysis of the degree of hypertrophy and number of spot welds present. Also by chi2 analysis, the degree of calcar atrophy was not significantly different between groups. The mean VAS score for pain at 24 months was 12.5 for the control and 12.1 for the treatment group. No significant differences were seen in any of the clinical categories of the SICOT Scale over the 24-month interval. CONCLUSION: The objective of TCP-coating--to increase the rate and amount of bony ingrowth while reducing the rate of calcar resorption in non-cemented THA--was not achieved by 24 months postoperatively in our study. PMID- 11764875 TI - Sentinel lymph-node biopsy for melanoma of the trunk and extremities: the McGill experience. AB - OBJECTIVE: To determine the effectiveness of sentinel lymph-node (SLN) biopsy for melanoma of the trunk and extremities. DESIGN: Case series review. SETTING: Royal Victoria Hospital, a Canadian university hospital. PATIENTS: Thirty-six patients (18 women and 18 men) seen between October 1996 and December 1998 with melanoma 1 mm or more in thickness with clinically negative lymph-node basins. Follow-up was 396 days. INTERVENTIONS: SLN biopsy. Technetium-99m filtered sulfur colloid (0.5 mCi) was injected intradermally around the melanoma or the excision scar 10 to 15 minutes before the surgical skin preparation. The identification of the SLN(s) was done with a hand-held gamma probe. Local anesthesia was used mostly for inguinal SLN biopsy whereas general anesthesia was usually required for axillary SLN biopsy. Preoperative lymphoscintigraphy was used only for trunk melanomas. OUTCOME MEASURES: Morbidity, successful identification of the sentinel node and locoregional recurrence. RESULTS: The mean age of patients at diagnosis was 53.4 years (range from 22-76 yr). The melanomas were distributed between the lower extremities (20 patients), upper extremities (8 patients) and trunk (8 patients). The mean Breslow thickness was 2.35 mm (range from 1-8 mm). Lymphoscintigraphy accurately localized the lymph-node drainage basin for trunk melanomas. In 1 patient the SLN could not be identified because the radiocolloid failed to migrate (failure rate 2.8%). The average number of SLNs removed was 1.97. Eight patients (22%) had sentinel nodes positive for malignant disease. The postoperative complication rate was 8.5%. Seven of 8 patients with positive SLNs underwent a complete node dissection (1 patient refused). Of the completion dissections only 2 patients had positive non-SLNs. All patients with positive nodes received interferon alpha-2b as adjuvant treatment. At follow-up, 34 patients are alive with no evidence of disease, 1 patient with a positive SLN is alive with distant metastatic disease and 1 patient with a negative SLN is dead of disseminated disease. CONCLUSION: SLN biopsy is a feasible technique with an acceptable failure rate and is thus a useful tool in the surgical management of melanoma. PMID- 11764876 TI - Sentinel lymph-node biopsy after previous wide local excision for melanoma. AB - OBJECTIVE: To document experience with sentinel lymph-node biopsy in patients who have already undergone a wide local excision for melanoma because in many centres previous wide excision has been a contraindication for sentinel lymph-node biopsy. DESIGN: A prospective cohort study. SETTING: A tertiary care academic cancer centre. PATIENTS: One hundred patients who presented with cutaneous melanoma (depth >1 mm or Clark level IV) after having undergone wide local excision of the primary lesion that was not situated in the head or neck. The follow-up was 3 years. INTERVENTIONS: Sentinel lymph-node biopsy. Patients with truncal melanoma had preoperative lymphoscintigraphy to document the nodal basins at risk. Technetium-99m sulfur colloid (0.5-1 mCi in 0.5 mL) was injected intradermally around the scar, and the sentinel lymph node was excised with the aid of a hand-held gamma detector. OUTCOME MEASURES: Accuracy of the biopsy and false-negative rates in this setting. RESULTS: Of the 100 patients, 44 had truncal and 56 had extremity lesions. The average tumour depth was 3.47 mm and 3.07 mm respectively. Thirty-one patients had a sentinel lymph node positive for melanoma metastasis. Biopsies were positive for melanoma in 18 (41%) truncal lesions and 13 (23%) extremity lesions. There were 3 (9%) false-negative sentinel lymph-node biopsies as diagnosed by clinically evident nodal disease subsequently appearing in the nodal basin subjected to biopsy. Two occurred in patients after large rotation flap closures of truncal lesions. The third patient had a subungual melanoma of the great toe. No disease was found in the 2 nodes dissected. Two of the 3 false-negative biopsy results were obtained before serial sections and immunohistochemical staining were used to examine the sentinel lymph nodes. CONCLUSIONS: Sentinel lymph-node biopsies can successfully identify clinically occult nodal metastases in patients who have had previous wide local excision of a melanoma, but the false-negative rate in patients with rotation flap closures should be taken into consideration. PMID- 11764877 TI - Snowboarding injuries in children. AB - OBJECTIVE: To study injury patterns of snowboarding trauma in children. DESIGN: A retrospective case series. SETTING: A major pediatric trauma centre. PATIENTS: A cohort of 113 children (97 boys, 16 girls), mean age 13.9 years, who sustained 118 injuries secondary to snowboarding. INTERVENTIONS: All fractures were treated by immobilization in a cast; 19 children required a closed reduction. OUTCOME MEASURES: Sex and age of patients, mechanism of injury, injury sustained, treatments and complications. RESULTS: Falls on the outstretched hand from a loss of balance accounted for 66 (57%) of the injuries, uncontrolled falls for 42 (36%) and collisions for 5 (4%). Seventy-nine percent of the injuries were to the upper extremity, whereas 7% were to the lower extremity. CONCLUSIONS: The predominance of snowboarding injuries of the upper extremity seen in children differs significantly from those in adults in whom lower extremity injuries are more common. PMID- 11764878 TI - Postprandial bloating after laparoscopic Nissen fundoplication. AB - OBJECTIVE: To evaluate the prevalence and possible contributing factors to postprandial bloating in patients having chronic gastroesophageal reflux disease (GERD) before and after laparoscopic Nissen fundoplication. DESIGN: A prospective cohort study. SETTING: A tertiary care teaching hospital. PATIENTS: Five hundred and seventy-eight patients with proven GERD. INTERVENTION: Laparoscopic Nissen fundoplication. OUTCOME MEASURES: Symptom severity scores for postprandial bloating and dysphagia, esophageal motility and 24-hour pH measurement before and at 6 months, 2 years and 5 years after laparoscopic Nissen fundoplication. RESULTS: Of the 598 patients, 436 (73%) reported some postprandial bloating before the procedure. The symptom score for bloating significantly improved after surgery (p < 0.0001). There were no significant differences in the lower esophageal sphincter basal pressures or 24-hour pH scores between those who reported improvement or worsening of their postprandial bloating. At 6 months after surgery, 54% of patients experienced postprandial bloating; of these, 49% reported improvement, 21% reported worsening and 30% reported no change in bloating symptoms compared with the preoperative state. Of the patients who reported worsening of postprandial bloating 6 months after surgery, 86 were reassessed 2 years after surgery and 71% reported improvement of this symptom over this time interval. CONCLUSIONS: Bloating is a common symptom in patients who suffer from chronic GERD. Laparoscopic Nissen fundoplication lessens the severity of this symptom in most patients. In a small subgroup of patients, antireflux surgery may exacerbate the bloating, but this improves over time. PMID- 11764879 TI - Children in crashes: mechanisms of injury and restraint systems. AB - OBJECTIVES: To explore the levels of protection offered to children involved in motor vehicle collisions. DESIGN: A joint study by the Children's Hospital of Eastern Ontario (CHEO) and Transport Canada, Ottawa, conducted in 2 phases: retrospective from 1990 to 1997 and prospective from 1998 to 2000. SETTING: CHEO, a university affiliated tertiary care centre. PATIENTS: Children admitted to CHEO between 1990 and 2000 with spinal trauma due to motor vehical crashes (MVCs). Phase I of the study involved analysis, in a series of 45 children after MVAs, by location of spinal injury versus belt type. Phase 2 was a prospective study of 22 children injured in 15 MVAs. INTERVENTIONS: A biomechanical assessment of the vehicle and its influence on the injuries sustained. MAIN OUTCOME MEASURES: The nature and extent of the injuries sustained, and the vehicle dynamics and associated occupant kinematics. RESULTS: The odds ratio of sustaining a spinal injury while wearing a 2-point belt versus a 3-point belt was 24 (95% confidence interval 2.0-2.45, p < 0.1), indicating a much higher incidence with a lap belt than a shoulder strap. CONCLUSIONS: Proper seat-belt restraint reduces the morbidity in children involved in MVCs. Children under the age of 12 years should not be front-seat passengers until the sensitivity of air bags has been improved. Three-point pediatric seat belts should be available for family automobiles to reduce childhood trauma in MVCs. PMID- 11764880 TI - Anal intraepithelial dysplasia and squamous carcinoma in immunosuppressed patients. AB - OBJECTIVE: To describe a treatment and follow-up protocol for HIV patients with anal dysplasia or warts, which are at risk of malignant change. DESIGN: An ongoing study of highly selected patients referred to a single surgeon. SETTING: The Colorectal and HIV/AIDS Clinics, University of Ottawa, General Campus. PATIENTS: Ninteen young men who presented with suspicious anal lesions and were referred to the Colorectal Clinic by the HIV/AIDS Clinic, which sees approximately 800 patients per year. OUTCOME MEASURE: Significance of dysplasia or carcinoma. RESULTS: Of the 19 patients, 14 had dysplasia, carcinoma-in-situ or invasive carcinoma. All were treated with multiple mapped cold biopsies and local or wide excision as indicated. Two patients with invasive carcinoma received radiotherapy or chemotherapy, or both. CONCLUSIONS: The incidence of dysplasia or the sequence by which dysplasia progresses to invasive carcinoma is unknown. Surveillance of HIV patients, especially those with nodules or warts, by flexible sigmoidoscopy and Papanicolaou smears every 3 to 12 months is recommended, depending on the severity of the anal lesion. PMID- 11764881 TI - Left paraduodenal hernia: an unusual cause of small-bowel obstruction. PMID- 11764882 TI - Inverted Meckel's diverticulum presenting as chronic anemia: case report and literature review. PMID- 11764883 TI - A simple technique for tying intracorporeal knots in laparoscopic surgery. PMID- 11764884 TI - Cost of pediatric trauma. PMID- 11764885 TI - Evidence-based practice. PMID- 11764886 TI - Bacteriocins: safe, natural antimicrobials for food preservation. AB - Bacteriocins are antibacterial proteins produced by bacteria that kill or inhibit the growth of other bacteria. Many lactic acid bacteria (LAB) produce a high diversity of different bacteriocins. Though these bacteriocins are produced by LAB found in numerous fermented and non-fermented foods, nisin is currently the only bacteriocin widely used as a food preservative. Many bacteriocins have been characterized biochemically and genetically, and though there is a basic understanding of their structure-function, biosynthesis, and mode of action, many aspects of these compounds are still unknown. This article gives an overview of bacteriocin applications, and differentiates bacteriocins from antibiotics. A comparison of the synthesis. mode of action, resistance and safety of the two types of molecules is covered. Toxicity data exist for only a few bacteriocins, but research and their long-time intentional use strongly suggest that bacteriocins can be safely used. PMID- 11764887 TI - Biosynthetic requirements for the repair of membrane damage in pressure-treated Escherichia coli. AB - Cells of Escherichia coli that survived pressure treatment at 400 MPa showed increased sensitivity to sodium deoxycholate or sodium chloride in the plating medium, implying that homeostatic or barrier functions associated with outer and cytoplasmic membranes, respectively, were impaired. Repair of such sublethal membrane damage occurred when cells were incubated at 37 degrees C in tryptone soya broth. Inhibitor studies indicated that repair of cytoplasmic membrane damage was energy-dependent and required RNA and protein synthesis, whereas repair of outer membrane damage occurred with no requirement for energy or RNA or protein synthesis. PMID- 11764888 TI - Campylobacter, Salmonella, Shigella and Escherichia coli in live and dressed poultry from metropolitan accra. AB - This study on the microbiology of chicken assessed a total of 97 live birds from three selected farms and 87 carcasses/chicken parts from two supermarkets, two open markets and one wholesale outlet (cold store) in the Accra metropolis. Campylobacter spp. were isolated from 14 (14.4%) gut contents of live birds from three farms. None of the frozen birds were positive for Campylobacter spp. These isolates were sensitive to most common antibiotics but not to ampicillin and tetracyclines. Salmonella spp. were isolated from 7 (7.2%) gut contents and 13 (6.8%) carcasses and were resistant to erythromycin. cefotiam, penicillin, ampicillin and cefadroxil. Samonella spp. had varied susceptibilities to nalidixic acid, chloramphenicol and minocyclin. No Shigella spp. was isolated from any of the live birds but 6 (6.9%) of imported chicken samples from the cold store and two markets were positive. Fosfomycin and chloramphenicol were the only antibiotics effective against these isolates. Twelve different Escherichia coli serovars were identified from the total of 21 positive samples. These, in order of magnitude isolated, are E. coli 0158 (14.3%), 0125 (14.3%), 025 (9.5%), 028ac (9.5%), 0159 (9.5%). 015 (9.5%), 0126 (9.5%), 063 (4.8%), 0143 (4.8%), 026 (4.8%), 078 (4.8%), 0164 (4.8%). Cefadroxil, ampicillin, penicillin, cefotiam, tetracycline and erythromycin were ineffective against all strains of E. coli isolated. Minocyclin was effective against all strains with the exception of E. coli 0159, 025, 0164 and 063, which were moderately susceptible. All strains with exception of E. coli 0164 were susceptible to fosfomycin. Nalidixic acid, chloramphenicol, kanamaycin, ceftrioxone and amoxycillin all showed varied effectiveness against the strains isolated. It is concluded that imported and locally produced chicken is a potential source of multiple-antibiotic-resistant enteropathogenic bacteria. Measures to improve the microbial quality of chicken are discussed. PMID- 11764889 TI - Relationship of mould count, ergosterol and ochratoxin A production. AB - The relationship between viable mould count, ergosterol content and ochratoxin A (OA) formation was studied at different inoculum concentrations of Aspergillus ochraceus NRRL 3174 and Penicillium verrucosum NRRL 3260 grown on sterile long grain enriched white rice as the substrate. Ergosterol was determined by extraction, saponification and quantification using high performance thin layer chromatography (HPTLC) with UV detection. Ergosterol and ochratoxin A were detected after 3 days of incubation and reached their maximum at 7-10 days of incubation. After that, a decline in the concentrations in both ergosterol and ochratoxin was observed. Ergosterol measurement by HPTLC appeared to be a useful method to detect fungal activity, which corresponded to ochratoxin production. Thus, the ergosterol assay may have a use as an early indicator of potential mycotoxin production. PMID- 11764890 TI - Outbreaks and sporadic cases of Salmonella serovar panama studied by DNA fingerprinting and antimicrobial resistance. AB - In the Principality of Asturias (PA), Spain. three Salmonella serovar Panama outbreaks were registered in August 1998. In order to achieve an accurate identification of the strains implicated in the outbreaks and to study the molecular epidemiology of this serovar in the PA, the isolates collected over 1990-1999 were examined by DNA fingerprinting and antimicrobial resistance analysis. The origin of the isolates was: human (65, of which 20 were associated with the three outbreaks), octopus (2), beef (2), eggs (7), poultry faeces (2), sea water (5), sewage (2) and unknown (1). Sixteen lineages were defined by ribotyping, enterobacterial repetitive intergenic consensus sequences analysis, and randomly amplified polymorphic DNA segment analysis. One lineage was endemic in the PA and was also represented by isolates from other Spanish regions. The organisms of this lineage can be differentiated (by resistance-, plasmid- and integron-profiles) into 19 types. The three outbreaks were caused by organisms falling into a single type (nalidixic acid-resistant, plasmid- and integron-free) belonging to the endemic lineage, which was associated with poultry as the reservoir. Isolates showing drug-resistance (71%) fell into six lineages and 23 types. Ten multidrug-resistant types carried class I integrons with three types of variable regions containing resistance gene cassettes. PMID- 11764891 TI - Structural and ultrastructural changes in yeast cells during autolysis in a model wine system and in sparkling wines. AB - This study shows the changes that occur during the autolysis of yeast in a model wine medium and in a sparkling wine after 12 months of aging, using Nomarsky Light Microscopy and Low Temperature Scanning Electron Microscopy (LTSEM). The size of the yeasts after 24 h of autolysis in a model medium is much smaller than when they are in the growth stage. With LTSEM. a large number of folds can be observed on the surface of the yeast and practically empty cells. Greater morphological changes, both structural and ultrastructural, can be observed in the yeast after 12 months of aging in wine than in the yeast after 24 h of induced autolysis. However, less of the cytoplasmic content of the yeast that has undergone autolysis in the wine was solubilized than that of the yeast after 24 h of autolysis in the model wine system. These findings indicate that autolysis of yeast in wine is a long-lasting process, which continues for at least 12 months. PMID- 11764892 TI - Real time detection of the tri5 gene in Fusarium species by lightcycler-PCR using SYBR Green I for continuous fluorescence monitoring. AB - LightCycler technology combines rapid in vitro amplification of DNA with real time detection and quantification of the amount of target molecules present in a sample. The system enables a 35-cycle PCR with 32 samples do be completed in 45 min, including quantification and identification of the product. It is therefore well suited for routine analysis of large numbers of samples in quality control and for defining HACCP concepts. Based on PCR primers specific to the tri5 gene, a quantitative group specific assay was established for Fusarium species producing trichothecenes. In the assay, SYBR Green I was used as fluorescent dye enabling real time detection of PCR products. Characterisation of the amplicons was achieved by melting point analysis (85 +/- 0.1 degrees C). Nonspecific products such as primer dimers could readily be distinguished from the product by their lower melting points. Composition of the amplification buffer was optimised and various hot start methods were tested in order to achieve the highest sensitivity of the assay. Uracil DNA glycosylase was added to prevent amplification of nonspecific products due to DNA carryover. The spectrum of species detected was generally in accordance with the results found in conventional PCR using the Tox5 primer pair. Reproducibility in six parallel experiments of the assay was determined to be 98% in the range between 0.05 and 6 ng of purified Fusarium graminearum DNA. The assay was used to analyse 30 wheat samples contaminated with toxigenic Fusarium spp. Contamination ranged from 0% to 78% as revealed by mycological analysis, and this is compared with results from the LightCycler. This is the first report on the use of the LightCycler system in combination with SYBR Green I for the quantification and identification of fungal DNA in pure cultures and sample material. PMID- 11764893 TI - Development and use of PCR primers for the investigation of C1, C2 and C3 enterotoxin types of Staphylococcus aureus strains isolated from food-borne outbreaks. AB - Staphylococcus aureus is a major food-borne pathogen in many countries. Enterotoxins produced by S. aureus strains include staphylococcal enterotoxins (SEs) A, B, C, D, E and G, H, I, etc. For SEC, in addition to the three major SEC subtypes, i.e., SEC1, C2 and C3, other molecular variants may exist. Although the detection methods and the distribution of SEA, B, C, D, E types of S. aureus in staphylococcal infections or food-borne outbreaks have been well documented, the differentiation method and the distribution of SEC subtypes in staphylococcal infections are rarely reported. In this study, four polymerase chain reaction (PCR) primers used in pairs (ENTC1/ENTCR, ENTC2/ENTCR and ENTC3/ENTCR) for the specific detection of SEC1, C2 and C3 genes of S. aureus strains were developed. When 39 SEC S. aureus strains isolated from fecal samples of randomly selected diarrheal patients associated with food-borne outbreaks in central Taiwan in 6 years (1995-2000) were analyzed, it was found that the major SEC subtypes for these S. aureus strains were SEC2 and C3. PMID- 11764894 TI - Identification of Pichia anomala isolated from yoghurt by RFLP of the ITS region. AB - Several packs of swollen retailed plain and flavoured yoghurt were examined. The most commonly found species was Pichia anomala, identified both by physiological tests and RFLP analysis of the rDNA internal transcribed spacer (ITS) region. The isolated strains did not ferment lactose and were positive for galactose fermentation, confirming the hypothesis that galactose-fermenting yeast could be the cause of spoilage in yoghurt. PMID- 11764895 TI - Identification of species in Aspergillus section Flavi based on sequencing of the mitochondrial cytochrome b gene. AB - The partial sequences of the mitochondrial (mt) cytochrome b gene (402 bp) were determined for species of Aspergillus section Flavi. On the basis of identities of DNA sequences, 77 strains were divided into seven DNA types, from D-1 to D-7. The type strains of A. sojae, A. parasiticus, A. flavus and A. oryzae together, A. tamarii, and A. nomius were placed in DNA types D-1. D-2, D-4, D-5 and D-7, respectively. These species could be differentiated from each other. Furthermore, two other DNA types, D-3 and D-6 were found. DNA type D-3 was closely related to A. parasiticus (D-2) and included one strain that deposited as A. flatus var. flavus and produced aflatoxins B and G. DNA types D-6 included one strain named A. flavus and closely related to A. tamarii. The observations of conidial wall texture by SEM (Scanning Electron Microscopy) supported the relationships derived from the cytochrome b gene. The production of aflatoxins was also examined. Using the DNA sequence of cytochrome b gene, several strains were reidentified. The derived amino acids sequences were all the same in the studied strains. The mt cytochrome b gene is useful and reliable in distinguishing and identifying the species in Aspergillus section Flavi. PMID- 11764896 TI - Evaluation of techniques for enrichment and isolation of Escherichia coli O157:H7 from artificially contaminated sprouts. AB - Because sprouted seed products are kept wet during and after production, have high levels of nutrients, and a neutral pH, they are subject to the outgrowth of pathogens such as Escherichia coli O157:H7. For these same reasons, these products also contain high levels of heterotrophic organisms and in particular coliform bacteria. Recent outbreaks have focused attention on the need to improve methodology for isolating this pathogen from sprouts. When 40 E. coli O157:H7 strains were grown in pure culture in enterohemorrhagic E. coli enrichment broth (EEB) as prescribed in the U.S. FDA-Bacteriological Analytical Manual (FDA-BAM) and in EEB modified by varying the cefixime concentration, outgrowth for all strains in EEB was inhibited at 0.05 mg/l but for only 2 of 40 strains when the cefixime level was adjusted to 0.0125 mg/l. These two enrichment formulae were compared to modified E. coli broth (mEC), modified Tryptic Soy Broth with 20 mg/l novobiocin (mTSB + N), modified Buffered Peptone Water (mBPW), and mBPW with added 10 mg/l acriflavin, 10 mg/l cefsulodin, and 8 mg/l vancomycin (mBPW + ACV) for isolation of E. coli O157:H7 from sprouts. These comparisons were performed using low-level (0.12 to 0.42 cfu/g) artificially contaminated alfalfa and mixed salad sprouts. After enrichment, two isolation methods were compared for recovery; direct plating to Tellurite-Cefixime Sorbitol MacConkey agar (TCSMAC) and immunomagnetic separation (IMS) (Dynabeads anti-E. coli O157, Dynal, Oslo, Norway) followed by plating to TCSMAC. In addition, an immunoprecipitin detection kit, VIP (BioControl, Bellevue, WA), was evaluated for detection after enrichment. We found that five of the six enrichments were equivalent for detection or recovery while one enrichment (mTSB + N without agitation) was less productive. Incubation for 24 h was more effective in recovering E. coli O157:H7 from sprouts than 6 h for all enrichment broths. Plating after IMS was more productive than direct plating at these low levels of contamination, yielding recovery in 70 of 90 trials compared to 37 of 90 trials without IMS for six enrichments. The sensitivity of VIP for detection of E. coli O157:H7 varied depending on the enrichment broth. Because of the rapid rate of growth of E. coli O157:H7 in mBPW, the high productivity of mBPW + ACV after 24-h enrichment and its compatibility with both IMS and detection with immunoprecipitin tests, mBPW + ACV at 42 degrees C with agitation was found to be the most promising enrichment protocol for testing sprouts. PMID- 11764897 TI - Factors influencing the detection and enumeration of Escherichia coli O157:H7 on alfalfa seeds. AB - Isolating Escherichia coli O157:H7 from batches of alfalfa seeds used to produce sprouts implicated in human illness has been difficult, perhaps due to nonhomogenous and very low-level contamination and inaccessibility of the pathogen entrapped in protected areas of the seed coat. We evaluated the effectiveness of various treatments in releasing E. coli O157:H7 from seeds. The influence of homogenization (blending or stomaching for 1 or 2 min), rinsing method (shaking for 5 min), soaking time (0. 1, 3, 6, or 15 h), soaking temperature (4 or 21 degrees C), and the addition of surfactants (0.1%, 0.5%, or 1.0% Tween 80 or Span 20) to rinse water was determined. Blending or stomaching for 1 or 2 min, and soaking for 1 h or longer at 4 or 21 degrees C, respectively, resulted in maximum release of E. coli O157:H7 from seeds. Soaking seeds at 37 degrees C for 15 h increased cell populations of E. coli O157:H7 by approximately 3.6 log10 CFU/g, likely due to bacterial growth. The maximum number of cells released from seeds by rinse water containing 1.0% Span 20 was at 21 degrees C, whereas at 37 degrees C, 0.1% or 0.5% Tween 80 was more effective. Detection of E. coli O157:H7 on seeds stored at 37 degrees C for up to 13 weeks and on sprouts derived from these seeds was compared. E. coli O157:H7 inoculated on seeds at 2.0 log10 CFU/g was detected after storage of seeds for up to 8 weeks at 37 degrees C and in sprouts produced from the seeds. The pathogen was not detected on seeds stored for 13 weeks at 37 degrees C and was not isolated from sprouts produced from these seeds. Identifying seed treatment methods that enhance removal of E. coli O157:H7 from alfalfa seeds can aid the isolation and enumeration of the pathogen on seeds. With a combination of optimal conditions for detecting the pathogen, i.e. soaking seeds for 1 h and pummeling seeds for 1 min, an enrichment step in modified tryptic soy broth (TSB), and the use of immunomagnetic beads for separation of E. coli O157:H7 cells, E. coli O157:H7 was detected in alfalfa seeds incubated at 37 degrees C for up to 8 weeks as effectively as in sprouts produced from the seeds. PMID- 11764898 TI - Suicide by firearms: a 15-year experience. AB - A retrospective review of 1704 cases of suicide involving firearms investigated by the Bexar County Medical Examiner's office between 1984 and 1998 was performed. The age distribution was similar in male and female victims, and the type of weapon was not associated with age. Approximately 78% of the victims used a handgun (87% of female and 76% of male victims). In 4.0% of head wound cases, the site of the entrance wound was the back of the head. Thus, this report refutes the common belief that all gunshot wounds to the back of the head represent homicides. In 1.9% of the cases, the wounds were inflicted at intermediate range. With handguns, the right temple was the most common site, but with rifles and shotguns, the most common site was the mouth. PMID- 11764899 TI - The application of histochemical methods to the age evaluation of skin wounds: experimental study in rabbits. AB - Enzyme histochemical methods allow determination of wound age, especially in the range of a few hours, and are used to distinguish between postmortem and antemortem skin wounds. The methods are based on the determination of the presence and changes of the enzyme reaction in the wound area. Increased activity of nonspecific esterases was observed approximately 1 hour after wounding and was followed by an increase in adenosine triphosphatase at approximately 2 hours and alkaline phosphatase at approximately 3.5 hours. Maximum enzyme activity was reached for nonspecific esterases at 24 hours, for adenosine triphosphatase at 20 hours, and for alkaline phosphatase at 32 hours after wounding. PMID- 11764901 TI - Heat-related mortality in selected United States cities, summer 1999. AB - As part of a public health response to severe heat waves in the midwestern and northeastern United States in the summer of 1999, the authors actively solicited the number of heat-related deaths from 38 medical examiner and coroner jurisdictions comprising 35 metropolitan areas to enumerate heat-related deaths in areas affected by heat waves. They also determined the usefulness of these data for surveillance and rapid investigation of heat-related deaths. A total of 334 heat-related deaths were reported during the study period of July 1 - August 31. Minor changes in data collection and diagnostic criteria in some medical examiner and coroner jurisdictions would allow for greater comparability among jurisdictions. The National Association of Medical Examiners' position paper on heat-related mortality diagnosis provides important guidance to medical examiners and coroners regarding the certification of heat-related deaths and may require some refinement to address certain issues. Among these are certifying manner of death and classifying potential causes of heat-related death not involving hyperthermia or heat stroke, but where heat is a potential contributing factor to death. Medical examiners and coroners are an important resource for heat-related mortality research, and improvements in data collection and reporting could yield tremendous benefits to our understanding of and interventions for heat-related deaths. PMID- 11764900 TI - Oronasal blood in sudden infant death. AB - Oronasal secretions are observed frequently in sudden infant death syndrome (SIDS), but overt blood is uncommonly reported. The literature on oronasal blood in sudden infant death is limited. The goal of this study was to determine the frequency of oronasal blood in sudden infant deaths and to examine possible causative factors. Oronasal blood was described in 28 (7%) of 406 cases of sudden infant death. Oronasal blood could not be attributed to cardiopulmonary resuscitation in 14 cases, including 10 (3%) of 300 cases of SIDS, 2 (14%) of 14 accidental suffocation cases, and 2 (15%) of 13 undetermined cases. Eight of the 10 infants in cases of sudden infant death were bedsharing: 5 with both parents, 2 between both parents. The infant in 1 SIDS case was from a family that had had three referrals to Child Protective Services. Oronasal blood not attributable to cardiopulmonary resuscitation occurs rarely in SIDS when the infant is sleeping supine in a safe environment. Bedsharing may place infants at risk of suffocation from overlaying. Oronasal blood observed before cardiopulmonary resuscitation is given is probably of oronasal skin or mucous membrane origin and may be a sign of accidental or inflicted suffocation. Sanguineous secretions that are mucoid or frothy are likely of remote origin, such as lung alveoli. The use of an otoscope to establish the origin of oronasal blood in cases of sudden infant death is recommended. PMID- 11764902 TI - Accidental sharp force injury fatalities. AB - The authors review all accidental sharp force injury deaths investigated at the Southwestern Institute of Forensic Sciences from 1990 to 1999. Twenty-two cases of accidental sharp force injury were identified, accounting for 0.29% of all accidental deaths (9,562) during the 10-year study period. Included in this series are 5 incised wounds, 11 stab wounds, 4 chop wounds, and 2 deaths caused by dog attacks. About half of the cases involved some type of motorized machinery. The victims' ages ranged from 2 years to 71 years, with most deaths occurring in older teenagers and younger adults. Male subjects (17) were involved much more frequently than female subjects (5). In 50% of the cases, ethanol or other drug use was a possible underlying contributing factor in the accident. The cases are briefly reviewed, and the importance of detailed investigation in manner-of-death certification is emphasized. PMID- 11764903 TI - Suicidal hanging within an automobile. AB - Accidental asphyxia related to cars has been described in different reports, but suicidal hanging in an automobile is very unusual. Two cases of suicidal hanging inside an automobile are described, illustrating an unusual form of hanging. In one case, the deceased used his belt as a ligature, and the point of attachment was the window of the car. The second victim used the safety belt of the passenger seat. In both cases, the automobile engine was turned off, all the windows were closed, and the door locks were blocked. The medicolegal cause of hanging was based on the scene of the investigation, police and witness reports, social history, autopsy findings, and toxicologic examinations. PMID- 11764904 TI - Internal current mark in a case of suicide by electrocution. AB - Fatalities caused by electrocution often lack specific morphologic evidence. Investigation of the death scene along with technical inspection of the electrical apparatus may help in clarifying the cause and manner of death. Cutaneous current marks may be the only sign of low voltage associated fatalities. The authors report a case of an electrician who committed suicide by electrocution using a time switch after oral ingestion of diazepam. Electrodes (coins) were fixed with adhesive tape at the height of the heart to the front and back of the left side of the chest. Autopsy revealed a blackish linear mark on the pleura parietalis of the inner side of the thoracic cavity, connecting the cutaneous current marks. Current-related and heat-related changes, such as hypercontraction bands of the intercostal muscles and coagulative changes of the perineurium of peripheral nerves, were found at histologic examination. Taking into consideration that the body had been under the influence of low-voltage current for 7 days, the morphologic alteration on the pleura parietalis was in accordance with an internal current mark, indicating the main route of current flow through the body. To the authors' knowledge, such a current-related phenomenon has not been reported to occur on an inner body surface before. PMID- 11764905 TI - Environmental hyperthermic infant and early childhood death: circumstances, pathologic changes, and manner of death. AB - Infant and early childhood death caused by environmental hyperthermia (fatal heat stroke) is a rare event, typically occurring in vehicles or beds. The aims of this study were to describe the demographics, circumstances, pathology, and manner of death in infants and young children who died of environmental hyperthermia and to compare these cases with those reported in the literature. Scene investigation, autopsy reports, and the microscopic slides of cases from three jurisdictions were reviewed. The subjects in 10 identified cases ranged in age from 53 days to 9 years. Eight were discovered in vehicles and 2 in beds. When the authors' cases were grouped with reported cases, the profile of those in vehicles differed from those in beds. The former were older, were exposed to rapidly reached higher temperatures, and often had more severe skin damage. The latter were mostly infants and were exposed to lower environmental temperatures. Hepatocellular necrosis and disseminated intravascular coagulation were reported in victims who survived at least 6 hours after the hyperthermic exposure. The consistent postmortem finding among nearly all victims was intrathoracic petechiae, suggesting terminal gasping in an attempt at autoresuscitation before death. The manner of death was either accident or homicide. Recommendations for the scene investigation are made. PMID- 11764906 TI - Diving-related fatalities caused by underwater explosions: a report of two cases. AB - The authors report two cases of diving-related water blast with fatal outcome resulting from nearby underwater explosions. Water blast with fatal outcome almost exclusively occurs in wars at sea. Underwater explosions are extremely rare in diving because of the limited exposure. Forensic findings in both cases reported included expected injuries to gas-filled organs such as the middle ear, lungs, and intestine; some rarely described injuries such as rupture of the liver, spleen, and kidneys; and also some lesions that were not found in a search of the literature: rupture of the heart and contusion of the hypophysis. Injuries caused by fatal underwater explosions should be carefully evaluated in forensic medicine to provide data that may support a criminal investigation. PMID- 11764907 TI - Fatal carbon monoxide poisoning after the detonation of explosives in an underground mine: a case report. AB - An unusual death caused by carbon monoxide poisoning after the detonation of explosives in an underground mine was investigated by the Office of the Medical Investigator of the State of New Mexico. The 50-year-old miner had 18 years of mining experience but no documented safety training. He collapsed approximately 20 minutes after entering the mine and working at the bottom of the single vertical shaft. The tight confines of the mine shaft hindered rescue personnel from reaching him, and the body was not recovered until 2 days later. The autopsy showed severe coronary artery atherosclerosis with remote and resolving myocardial microinfarcts, as well as the characteristic pink lividity of carbon monoxide poisoning, which was confirmed by laboratory analysis. Detailed investigation of the scene revealed no sources of carbon monoxide other than the explosives. The case represents an uncommon cause of death in mining that may have been avoided through the use of proper safety procedures, and illustrates the importance of recognizing the many sources of carbon monoxide. PMID- 11764908 TI - Potential confusion arising from materials presenting as possible human remains. AB - The accurate identification of human tissues is an important part of forensic science, but may be difficult when specimens are small, fragmented, or burned. A wide variety of materials may be submitted as human, including parts of animals and nonorganic materials. Two cases involving a plastic fetal skeleton and a rubber fetus are described, which were initially considered to represent human remains, thus initiating police investigations for possible concealed stillbirth or infanticide. In one case, the remains were so deceptively real in appearance that hospital personnel initiated fibroblast cultures from an "umbilical cord". A third case of mineral concretions that resembled a human hand is also described. These cases demonstrate that protocols should be in place for the rapid assessment of all suspected human remains by pathologists, so that nonhuman material can be rapidly excluded, and police investigations terminated. PMID- 11764909 TI - DNA analysis of abortion material assisted by histology screening. AB - In cases of rape leading to fertilization, paternity testing can retrospectively identify the assailant. Abortion material commonly represents a mixture of maternal and fetal tissue and blood, which cannot be differentiated with the naked eye. Consequently, DNA typing of abortion material may be complicated, including band overlap if maternal tissue predominates. Therefore, histology screening of the abortion content for typical fetal tissue components, such as chorionic villi, followed by selected DNA typing of this sample is suggested. This combined approach is illustrated by a selected case demonstrating the reliability and concurrence of the histology and genetic results. PMID- 11764910 TI - Detection of species of graft in xenotransplants using arbitrary primed polymerase chain reaction. AB - Because of a shortage in the availability of human organs, xenografts have been attempted in humans with cardiac, renal, and hepatic failure, despite limited success. Use of xenografts, however, is regulated under law in various countries. In xenotransplant cases related to violation of transplantation law, determination of species of the source of tissue and organ(s) becomes highly essential. Random amplified polymorphic DNA (RAPD) protocols using six sets of arbitrary short-sequenced primers have been standardized for verifying claims of porcine cardiac and renal grafts in human transplantation cases. Six arbitrary primers used were found to generate unique amplicon patterns at 36 degrees C annealing temperature. Among the selected primers, a single primer set having the sequence 5'- GGTGCGGGAA -3' is found to be the most informative in discerning porcine tissue contamination in humans. The patterns obtained were consistent for a particular genome. The grafted organs in the studied case were analyzed to be of porcine origin. PMID- 11764911 TI - An approach to dissecting the congenitally malformed heart in the forensic autopsy: the value of sequential segmental analysis. AB - The demonstration of congenital heart disease at autopsy necessitates the careful preservation and examination of the heart, the vessels, and their connections. Techniques preserving these connections and using a reproducible and systematic approach are preferred. The Rokitansky method of organ block dissection, in combination with a system of heart examination termed sequential segmental analysis, provides such an approach. This study is based on the examination of heart specimens accessioned into the Frank E. Sherman, M.D., and Cora C. Lenox, M.D., Heart Museum (containing approximately 2400 specimens) of the Pathology Department, Children's Hospital of Pittsburgh. Specimens received in consultation during a 25-year period from hospitals and coroners'/medical examiners' offices were examined, and the corresponding reports were reviewed. Of 46 total heart specimens examined (1975-1999), 29 (63%) were dissected properly or left intact for dissection at Children's Hospital of Pittsburgh, and 17 (37%) were incorrectly dissected for the demonstration of congenital heart disease. Of these 17 cases, 11 (24%) displayed dissection errors, which did not hinder a complete diagnosis, 3 cases (6.5%) had errors that enabled only an incomplete diagnosis, and in 3 cases (6.5%), no diagnosis of congenital heart disease could be made. Dissection mistakes and means of avoiding them are discussed. Review of medical and family history, external and internal examination, and a reproducible and sequential method of examining the heart and its connections enables documentation of even the most complex cardiovascular anomalies. PMID- 11764912 TI - A homicide in the Ukraine: DNA-based identification of a boiled, skeletonized, and varnished human skull, and of bone fragments found in a fireplace. AB - In an apartment, bone fragments were found in a fireplace. Furthermore, a varnished skull was found elsewhere in the same apartment. The tenant confessed to a murder and stated that the head of a victim, a girl, was boiled for 12 hours. He stated that the soft tissue was then removed and the skull was varnished. Other parts of the body were burned to ashes in an open field. Comparison of loci D19S252, CD4, CYAR04, TII01, F13A01, F13B, and D6S366 from the skull and the bone remains to loci of the mother of a missing girl showed that the skull came from that missing child. Biological maternity was calculated as 99.99%. The bone pieces were DNA typed as male and did not share alleles with the mother in several systems. Therefore, they belonged to a different (human) victim. PMID- 11764913 TI - Retinal hemorrhages: evidence of abuse or abuse of evidence? PMID- 11764914 TI - Sudden infant death syndrome. PMID- 11764915 TI - Fatal pediatric head injuries caused by short distance falls. PMID- 11764917 TI - Death resulting from asthma associated with sertraline "overdose". PMID- 11764918 TI - Biological reactive intermediates and mechanisms of cell death. PMID- 11764919 TI - Chemistry and biological activity of novel selenium-containing compounds. PMID- 11764920 TI - Structure activity relationships for the chemical behaviour and toxicity of electrophilic quinones/quinone methides. PMID- 11764921 TI - Formation and fate of reactive intermediates of haloalkanes, haloalkenes, and alpha-haloacids. PMID- 11764922 TI - Human epoxide hydrolase is the target of germander autoantibodies on the surface of human hepatocytes: enzymatic implications. PMID- 11764923 TI - Structural characterisation of the main epichlorohydrin-guanosine adducts. PMID- 11764924 TI - Adducts of the chloroform metabolite phosgene. PMID- 11764925 TI - Oxygenation of arachidonic acid by cyclooxygenases generates reactive intermediates that form adducts with proteins. PMID- 11764926 TI - Use of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation. PMID- 11764927 TI - Inhibition by ticlopidine and its derivatives of human liver cytochrome p450. Mechanism-based inactivation of CYP 2C19 by ticlopidine. PMID- 11764928 TI - Microperoxidase 8 (mp8) as a convenient model for hemoproteins: formation and characterisation of new iron(II)-nitrosoalkane complexes of biological relevance. PMID- 11764929 TI - Hemoglobin adducts in rats chronically exposed to room-aged cigarette sidestream smoke and diesel engine exhaust. AB - Under controlled conditions with exaggerated concentrations of environmental aerosols, the biologically effective dose markers suggested in the literature as being specific for ETS (i.e., HPB Hb adducts for TSNA exposure) and DEE (i.e., l aminopyrene Hb adducts for l-nitropyrene exposure) did not respond. A slight but dose-dependent increase in 4-ABP Hb adduct levels was seen in RASS-exposed rats. PMID- 11764930 TI - DNA microarray reveals increased expression of thioredoxin peroxidase in thioredoxin-1 transfected cells and its functional consequences. AB - The mammalian thioredoxins are a family of small redox proteins that undergo NADPH dependent reduction by thioredoxin reductase. Reduced thioredoxins reduce oxidized cysteine groups on proteins including transcription factors to increase their binding to DNA, and is a source of reducing equivalents for enzymes such as thioredoxin peroxidase which removes H2O2 and alkyl peroxides. Thioredoxin-1 is over expressed in many human tumors where it is associated with aggressive tumor growth, inhibited apoptosis and decreased patient survival. Transfection of cells with thioredoxin-1 has been shown to increase cell growth and inhibit apoptosis. We have used DNA micro array to investigate the effects of thioredoxin-1 transfection on the expression of a panel of 520 redox, apoptosis and cell growth related genes in MCF-7 human breast cancer cells. One of the genes whose expression was increased as a result of thioredoxin-1 over expression was thioredoxin peroxidase-2. This increase was confirmed by Northern blotting. Transfection of mouse WEHI7.2 thymoma cells with human thioredoxin peroxidase-2 was found to protect the cells from apoptosis induced by H2O2 but not from apoptosis induced by dexamethasone, doxorubicin or etoposide. Thus, increased thioredoxin peroxidase-2 expression does not explain the widespread antiapoptotic effects of thioredoxin-1. PMID- 11764931 TI - Reactive nitrogen species and proteins: biological significance and clinical relevance. PMID- 11764932 TI - Bicarbonate enhances nitration and oxidation reactions in biological systems- role of reactive oxygen and nitrogen species. PMID- 11764933 TI - Nitric oxide and peroxynitrite in ozone-induced lung injury. AB - One of the hallmarks of the inflammatory response associated with tissue injury is the accumulation of macrophages at sites of damage. These cell types release proinflammatory cytokines and cytotoxic mediators to destroy invading pathogens and initiate wound repair. However, when produced in excessive amounts, these macrophage-derived mediators may actually contribute to tissue injury. This process involves both direct damage to target tissues and amplification of the inflammatory response. One group of macrophage-derived mediators of particular interest are reactive nitrogen intermediates including nitric oxide and peroxynitrite which have been implicated in tissue injury induced by a variety oftoxicants. Our laboratory has been investigating the role of reactive nitrogen intermediates in lung injury induced by oxidants such as ozone. Inhalation of ozone causes epithelial cell damage and Type II cell hyperplasia. This is associated with an accumulation of activated macrophages in the lower lungs which we have demonstrated contribute to toxicity. To analyze the role of macrophage derived reactive nitrogen intermediates in ozone toxicity, we used transgenic mice lacking the gene for inducible nitric oxide synthase (NOSII). Treatment of wild type control animals with ozone (0.8 ppm) for 3 hr resulted in an increase in bronchoalveolar lavage (BAL) fluid protein reaching a maximum 24-48 hr after exposure. This was correlated with increased expression of NOSII protein and mRNA by alveolar macrophages and increased production of nitric oxide as well as peroxynitrite. Ozone inhalation also resulted in the appearance of nitrotyrosine residues in the lungs, an in vivo marker of peroxynitrite-induced damage. In contrast, in NOSII knockout mice, BAL protein was not increased demonstrating that these mice were protected from ozone-induced epithelial injury. Moreover, alveolar macrophages from the transgenic mice did not produce nitric oxide or peroxynitrite even after ozone inhalation. There was also no evidence for the formation of nitrotyrosine in lung tissue. These data indicate that ozone-induced lung injury is mediated by reactive nitrogen intermediates. PMID- 11764934 TI - Antioxidant reactions of green tea catechins and soy isoflavones. PMID- 11764935 TI - Reactive oxygen species analysis in gastritis patients and p53 methylation analysis in gastric tumor cell line AGS infected by Helicobacter pylori. PMID- 11764936 TI - Biological reactive intermediates that mediate chromium (VI) toxicity. AB - 1. Addition of Cr VI (dichromate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential and lysosomal membrane rupture before hepatocyte lysis occurred. 2. Cytotoxicity was prevented by "ROS" scavengers, antioxidants, and glutamine (ATP generator). Hepatocyte dichlorofluorescin oxidation (to determine ROS/Cr V formation) was inhibited by mannitol (a hydroxyl radical scavenger) or butylated hydroxyanisole and butylated hydroxytoluene (antioxidants). 3. The Cr VI reductive mechanism required for toxicity are not known. Cytotoxicity was also prevented by cytochrome P450 inhibitors, particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase. This suggests that P450 reductase and/or reduced cytochrome P450 contributes to Cr VI reduction to Cr IV. 4. Glutathione depleted hepatocytes were resistant to Cr (VI) toxicity and much less dichlorofluorescin oxidation occurred. Reduction of dichromate by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Mn II (a Cr IV reductant ). Cr VI induced cytotoxicity and ROS formation was also inhibited by Mn II which suggests that Cr IV and Cr IV.GSH mediate "ROS" formation in isolated hepatocytes. 5. In conclusion Cr VI cytotoxicity is associated with mitochondrial/lysosomal toxicity by the biological reactive intermediates Cr IV and "ROS". PMID- 11764937 TI - Involvement of peroxynitrite on the early loss of p450 in short-term hepatocyte cultures. AB - The biological chemistry of nitric oxide (NO) in the oxygenated cellular environment is extremely complex. It involves the direct interaction of NO with specific biomolecules and the so-called indirect effects, due to secondary more potent oxidant species derived from NO which are also able to react with DNA, lipids, thiols and transition metals (Wink et al., 1996; Nathan, 1992). In addition to its regulatory role as a signalling molecule (Nathan, 1992; Moncada and Palmer, 1991) it has become evident that NO (or NO-derived species) is a critical factor involved in various toxicological mechanisms (Wink et al., 1996; Wang et al., 1998; Estevez et al., 1999; Wink et al., 1999). Some controversy exists however about the damaging vs. protective actions of NO on oxidative injury, whose biological significance in living cells and tissues remains still ill defined. Research in this laboratory (Lopez-Garcia, 1998; Lopez-Garcia and Sanz-Gonzalez, 2000) has shown that NO synthesis is significantly activated in hepatocytes from control rats following isolation by the classical collagenase based procedure. NO overproduction appears to be due to the very early activation of liver constitutive Ca2+-dependent NO synthase (cNOS). Previous results have also provided first experimental evidence for the direct involvement of endogenously generated NO as a causal factor responsible for important phenotypic changes commonly observed in short-term cultured hepatocytes, which includes the early impairment of hepatocyte mitochondrial function--i.e., transient cell energy depletion--and glucose metabolism, and the well-known quick and irreversible loss of P450 content (Lopez et al. 1987; Lopez-Garcia, 1998). This study aims to further characterise the mechanisms underlying this phenomenon. Results show that the hepatocyte isolation procedure (the commonly employed collagenase-based two step liver perfusion method) induces strong oxidative stress that lasts for at least 4 h in culture and involves both oxygen-derived (ROS) and nitrogen-derived (RNS) reactive species. On the basis of the combined use of dihydrorhodamine 123 (DHR) as a probe and L-NAME (N(G)-nitro-L-arginine methyl ester) to efficiently block NO synthesis, the analysis of the amount, the time-course pattern, and the nature of the species involved support the view that peroxynitrite* (PN) is readily formed within the early culture hours. Immunodetection of protein bound 3-nitrotyrosine provides direct evidence for PN generation upon hepatocyte isolation: several nitrated protein bands--most already present after only 30 min of liver perfusion and quantitatively increasing for the first 2 hours in culture--have been identified as preferential PN protein targets in the different cellular compartments. Since the early inhibition of NO synthesis is enough to provide full maintenance of the hepatocyte initial P450 content, results support the view that PN--while not affecting cell viability and monolayer development--is the main species likely responsible for the early loss of P450 in short-term cultured hepatocytes. PMID- 11764938 TI - Lack of correlation between CYP2A6 genotype and smoking habits. PMID- 11764939 TI - Free radical lipid peroxidation and monooxygenase activity in experimental influenza virus infection after treatment with rimantadine. PMID- 11764940 TI - Oxidative stress and the structure/activity relationships of ergopeptide alkaloids. PMID- 11764941 TI - Multiple oxidative stress parameters are modulated in vitro by oxygenated polycyclic aromatic hydrocarbons identified in river sediments. PMID- 11764942 TI - 1,N6-etheno-2'-deoxyadenosine adducts from trans, trans-2,4-decadienal and trans 2-octenal. PMID- 11764943 TI - Use of structure-activity relationships for probing biochemical mechanisms: glutathione transferase zeta conjugation of haloacids. PMID- 11764945 TI - NAD(P)H:quinone oxidoreductase (NQO1) protects astroglial cells against L-dopa toxicity. PMID- 11764944 TI - Hydrogen peroxide supports hepatocyte P450 catalysed xenobiotic/drug metabolic activation to form cytotoxic reactive intermediates. AB - 1. A H2O2 generating system markedly increased the cytotoxicity of catechols, hydroquinone, in isolated hepatocytes, but not in P450 inhibited hepatocytes. 2. H2O2 or NADPH supported microsomal catalysed GSH conjugate formation with catechols or hydroquinone. Cytochrome P450 inhibitors inhibited conjugate formation. However, superoxide dismutase inhibited NADPH, but did not affect H2O2 supported GSH conjugate formation. The conjugate formed with dihydrocaffeic acid was identified as a mono-GSH conjugate indicating that the o-quinone was the major metabolite formed. 3. Dopamine (a catecholamine) induced cytotoxicity was prevented by inhibitors of monoamine oxidase (MAO) or P450, but was markedly increased by hepatocyte catalase inhibition or NAD(P)H:quinone oxidoreductase inhibition. This suggests that H2O2 formed by the mitochondrial metabolism of monoamine oxidase then oxidised dopamine to cytotoxic o-quinone catalysed by P450. Dihydrocaffeic acid cytotoxicity was also increased by the monoamine oxidase substrate tyramine. 4. It is concluded that polyphenolics are oxidised by H2O2/P450 in hepatocytes to form quinone metabolites. PMID- 11764946 TI - GSH-dependent redox regulation and antioxidant enzymes in the formation of resistance to doxorubicin in K562 human erythroleukemia cells. PMID- 11764947 TI - Opposite effects of oxidative stress on endothelial cell lines (ECV 304 and EAhy 926) interaction with extracellular matrix. PMID- 11764948 TI - Hepatocyte lysis induced by environmental metal toxins may involve apoptotic death signals initiated by mitochondrial injury. AB - Addition of CdCl2, HgCl2 or K2Cr2O7 to isolated hepatocytes caused a rapid increase in reactive oxygen species ("ROS") formation and a decline in mitochondrial membrane potential. Later lipid peroxidation and cell lysis ensued. Cytotoxicity was prevented by "ROS" scavengers and various inhibitors of the mitochondrial permeability transition (MPT) eg. cyclosporin A, carnitine or trifluoperazine. Antioxidants prevented hepatocyte lysis induced by CdCl2, K2Cr2O7 but not HgCl2. Hepatocyte lysis was also prevented by various apoptosis inhibitors eg, cycloheximide, dactinomycin and a tetrapeptide caspase 3 inhibitor which suggests that metal induced hepatocyte lysis involves apoptotic death signals initiated by MPT and "ROS". PMID- 11764949 TI - Quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. PMID- 11764950 TI - Preventive effect of vitamin E on the processes of free radical lipid peroxidation and monooxygenase enzyme activity in experimental influenza virus infection. PMID- 11764951 TI - Lysosomal oxidative stress cytotoxicity induced by nitrofurantoin redox cycling in hepatocytes. AB - 1. The enzymes responsible for the reductive activation of NFT are not known. We have now shown that under aerobic conditions, inhibitors of cytochrome P450 or P450 reductase but not DT diaphorase prevented NFT induced cytotoxicity and reactive oxygen species ("ROS") formation. This suggests that NFT was reductively activated by reduced cytochrome P450 and/or P450 reductase. 2. The subcellular organelle oxidative stress effects leading to cytotoxicity are not known. Hepatocyte mitochondrial membrane potential was only slightly decreased by NFT before cytotoxicity ensued. However NFT induced lysosomal damage and hepatocyte protease activation. Endocytosis inhibitors, lysosomotropic agents or lysosomal protease inhibitors also prevented NFT induced cytotoxicity. 3. Lipid peroxidation also preceded cytotoxicity. Furthermore desferoxamine (a ferric chelator), antioxidants or ROS scavengers (catalase, mannitol, TEMPOL or dimethylsulfoxide) prevented NFT cytotoxicity. 4. It is concluded that H2O2 reacts with lysosomal Fe(+2) to form "ROS" which causes lysosomal lipid peroxidation, membrane disruption, protease release and cell death. PMID- 11764952 TI - Scavenging and antioxidant effects of estrogen derivatives in cholesterol-fed rabbits. PMID- 11764953 TI - Inhibition of oxidative damage of red blood cells and liver tissue by genistein 8C-glucoside. PMID- 11764954 TI - Effects of several wine polyphenols on lipid peroxidation and oxygen activation in rat liver microsomes. PMID- 11764955 TI - Chromosome damage from biological reactive intermediates of benzene and 1,3 butadiene in leukemia. PMID- 11764956 TI - The antitumor agent ecteinascidin 743: characterization of its covalent DNA adducts and chemical stability. AB - Ecteinascidin 743 (Et 743), a natural product derived from the Caribbean tunicate Eteinascidia turbinata, is a potent antitumor agent currently in phase II clinical trials. Et 743 binds in the minor groove of DNA, forming covalent adducts by reacting with N2 of guanine. Although DNA is considered to be the macromolecular receptor for Et 743, the precise mechanism by which Et 743 exerts its remarkable antitumor activity has not yet been elucidated. The aim of this study is to provide a rationale for the antitumor activity of Et 743 by studying its fundamental interactions with DNA at the molecular level. First, DNA structural distortions induced by Et 743 were characterized using gel electrophoresis. Surprisingly, Et 743 bends DNA toward the major groove, a unique feature among DNA-interactive agents that occupy the minor groove. Second, in order to gain further insight into the molecular basis behind the apparent sequence selectivity of Et 743, the stability and structure of Et 743 adducts at different target sequences were determined. On the basis of this data, the overall stability of the Et 743-DNA adducts was found to be governed by the DNA target sequence, where the inability of Et 743 to form optimum bonding networks with its optimum recognition sites leads to the formation of an unstable adduct. Consequently, the reaction of Et 743 with DNA is reversible, and the rate of the reverse reaction is a function of the target and flanking sequences. The results from this study demonstrate that Et 743 differs from other DNA alkylating agents by its effects on DNA structure and sequence-dependent chemical stability. This information provides important insight into the underlying mechanisms for its unique profile of antitumor activity. PMID- 11764957 TI - Design of DNA damaging agents that hijack transcription factors and block DNA repair. PMID- 11764958 TI - The potential role of topoisomerase II inhibition in hydroquinone-induced alterations in the maturation of mouse myeloblasts. PMID- 11764959 TI - Design and characterization of a novel "family-shuffling" technology adapted to membrane enzyme: application to P450s involved in xenobiotic metabolism. PMID- 11764960 TI - One-electron reduction of quinones by the neuronal nitric-oxide synthase reductase domain. PMID- 11764961 TI - Purification, biochemical characterization and comparative enzyme kinetics of recombinant human CYP2D6 1 and CYP2D6 2 variants. PMID- 11764962 TI - Structure toxicity relationships--how useful are they in predicting toxicities of new drugs? AB - This chapter provides just a few newer examples of structural moieties found in drugs that have been associated with reactive metabolite formation and toxicities. For a discussion of several other structures in drugs that undergo metabolic activation to reactive intermediates, the reader is directed to previous volumes in this series and other chapters in this book, as well as a previous condensed review (Nelson, 1982). Since that review, some new knowledge allows us to better predict that some structural moieties are more likely than others to form drug reactive metabolites that may be involved in causing toxic effects in humans. For example, most aniline-, thiophene-, and nitroaromatic containing drugs have had a relatively high incidence of adverse effects, and it would be prudent in the drug discovery process to avoid these substructures if possible. However, as illustrated by the case of olanzapine, these structures may be important for potent activity, and could therefore be beneficial in some cases. The glitazones represent a new class of drugs with a unique thiazolidinedione structure. This raises two important points. First, it demonstrates how limited our knowledge base is in regard to structure toxicity relationships when new structures are introduced. Our approaches must be very empirical and are far from quantitative for the reasons outlined in the introduction. Secondly, the glitazones point out the importance of benefit/risk considerations. This was a new structural class of drugs with a unique spectrum of action that is very beneficial in the treatment of a major disease. Despite some suspected risk of toxicity, based on early trials, troglitazone was approved for use with careful monitoring. This author believes that was the right decision, as was the decision to withdraw the drug when the risk became unacceptable, especially with the introduction of safer alternatives. If this were just another NSAID (e.g., bromfenac), there would be little reason for approval. In summary, as I pointed out previously (Nelson, 1982), with our limited knowledge of structure toxicity relationships, we can only make reasonable judgments as to risk assessment of a new drug in humans, and hope that we neither release a dangerous chemical entity nor, as importantly, abort an effective one. PMID- 11764963 TI - Inhibitory effects of roquefortine on hepatic cytochromes P450. PMID- 11764964 TI - Association of cytochromes P450 1A2 and 2B4: are the interactions between different P450 species involved in the control of the monooxygenase activity and coupling? PMID- 11764965 TI - Inactivation of polymorphic variants of human glutathione transferase zeta (hGSTZ1-1) by maleylacetone and fumarylacetone. PMID- 11764966 TI - Structure-activity relationships of cyclotetrapeptides: interaction of tentoxin derivatives with three membrane proteins. PMID- 11764967 TI - Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. PMID- 11764968 TI - Effect of the microsomal system on quinone redox cycling, oxygen activation, and lipid peroxidation. PMID- 11764969 TI - Reaction of nucleic acids with triformylmethane; a novel DNA-modifying agent. PMID- 11764970 TI - Are blood-brain interfaces efficient in protecting the brain from reactive molecules? PMID- 11764971 TI - The roles of P-glycoprotein and MRP1 in the blood-brain and blood-cerebrospinal fluid barriers. PMID- 11764972 TI - Are dopamine, norepinephrine, and serotonin precursors of biologically reactive intermediates involved in the pathogenesis of neurodegenerative brain disorders? PMID- 11764974 TI - Caspase cascades in chemically-induced apoptosis. PMID- 11764973 TI - Serotonergic neurotoxicity of methylenedioxyamphetamine and methylenedioxymetamphetamine. PMID- 11764975 TI - Spermatogenesis by Sisyphus: proliferating stem germ cells fail to repopulate the testis after 'irreversible' injury. AB - 2,5-Hexanedione is the toxic metabolite resulting from oxidation of the commonly used solvents n-hexane and methyl n-butyl ketone. Exposure to 2,5-hexanedione or its precursors results in a slowly progressive peripheral polyneuropathy and testicular injury. The chemical basis of the injury involves reaction of 2,5 hexanedione with protein amines, such as the epsilon-amine of lysine, to form pyrroles which further react to form protein-protein crosslinks. The target cell of injury in the testis is the supportive cell in the seminiferous epithelium, the Sertoli cell. A major function of the Sertoli cell is to nurture the dependent germ cell population by secreting seminiferous tubule fluid. 2,5 Hexanedione-induced crosslinking of the microtubule subunit protein, tubulin, leads to altered Sertoli cell microtubule-dependent transport and deficient formation of seminiferous tubule fluid, compromising germ cell viability. In an established model of testicular injury, rats are exposed to 1% 2,5-hexanedione in the drinking water for a period of 3-5 weeks. Three weeks after initiating exposure, decreased seminiferous tubule fluid secretion initiates a wave of germ apoptosis which peaks during the 5th week. The germ cell content of the injured testis continues to decline after cessation of the exposure, reaching a nadir during the 12th week. From this time onward, the testis is severely atrophic with less than 1% of seminiferous tubules in a testicular cross section containing germ cells more advanced than spermatogonia. Interestingly, this persistent state of post-injury 'irreversible' atrophy in the rat is characterized by the presence of a proliferating stem germ cell population which produces differentiating spermatogonia which then die by apoptosis. Serial cross sections of bromodeoxyuridine-labeled testis were analyzed to determine the kinetics of stem germ cell proliferation. Approximately 40% of stem cells (identified as single cells in the seminiferous epithelium) were actively proliferating with a cell cycle time of 8-14 days. Analysis of the total germ cell population present and modeling using the known cell cycle times of differentiating spermatogonia indicated a block in differentiation at the level of type A3/A4 spermatogonia. Quantitation of the frequency of apoptosis indicated that all of the germ cells died prematurely by this mechanism. Leuprolide is a gonadotropin-releasing hormone agonist which produces a profound suppression of testosterone levels with chronic administration. When delivered as a series of 3 depot injections 24 days apart, leuprolide resulted in a partial reversal of the 2,5-hexanedione-induced persistent atrophy. The reinitiation of spermatogenesis follows a lowering of the intratesticular testosterone concentration, indicating that intratesticular testosterone is at least partially responsible for the persistent atrophy. The efficacy of leuprolide-induced reversal of the persistent atrophy decreases with time after injury, suggesting that atrophic seminiferous tubules are initially capable of recovery and then enter a state of irreversible injury. Injection of ethane dimethane sulfonate at the beginning of leuprolide treatment eliminated Leydig cells during therapy and ablated the recovery of spermatogenesis, indicating that a Leydig cell-associated paracrine factor is required to restart spermatogenesis. The rat, therefore, has multiple states of testicular germ cell proliferation: normal spermatogenesis and at least two forms of persistent atrophy (leuprolide reversible and leuprolide non-reversible). Partial reversal of the persistent atrophy can be achieved by lowering intratesticular testosterone. Ongoing experiments are designed to address the role of the Leydig cell in post-injury recovery, and to further characterize the molecular events contributing to the different states of persistent atrophy. PMID- 11764976 TI - The interaction of 1,4-benzoquinone, a bioreactive intermediate of benzene, with three proteins essential for differentiation/maturation of the mouse myeloid stem cell. PMID- 11764977 TI - Hematopoietic stem and progenitor cells as targets for biological reactive intermediates. PMID- 11764978 TI - Biological reactive intermediates in drug discovery and development: a perspective from the pharmaceutical industry. PMID- 11764979 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lung and effect of cigarette smoke exposure on in vivo metabolism to biological reactive intermediates. PMID- 11764980 TI - Pharmacokinetics of benzene following an oral or intradermal dose in FVB and Tg.AC mice. PMID- 11764981 TI - Metabolism of the food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in human hepatocytes. PMID- 11764982 TI - Preventive effect of selenium on T-2 toxin membrane toxicity. AB - T-2 toxin, one of the major toxic trichothecene mycotoxines, has been shown to cause effects such as inhibition of protein synthesis and impairement of mitochondrial function. The use of T-2 toxin as chemical warfare in south east Asia and Iran has been reported . It has been suggested that T-2 toxin may mediate its toxic effect via the cell membrane, but mechanism of action is poorly understood. In cytotoxicity studies, erythrocytes are an excellent model system. In the present study different doses of sodium selenite were injected into male albino mice for 6 days every 48 h. Blood samples were taken from experimental and control groups (normal saline). The red cells were counted in isotonic phosphate buffer containing different doses of T-2 toxin. The mixture was incubated at 37 degrees C for 4 h. The results indicate that selenium is able to prevent erythrocyte membrane damage induced by T-2 toxin. The protective effect of selenium may be due to its membrane stabilizing properties, although inhibition of lipid peroxidation is likely, too. PMID- 11764983 TI - Modulation influence of p-chloromercuribenzoate on plasma membrane Na+-Ca2+ exchanger of the secretory cells of chironomus larvae salivary gland. PMID- 11764984 TI - Tobacco toxicology revisited. PMID- 11764985 TI - Functional genomics of oxidant-induced lung injury. AB - In summary, acute lung injury is a severe (>40% mortality) respiratory disease associated with numerous precipitating factors. Despite extensive research since its initial description over 30 years ago, questions remain about the basic pathophysiological mechanisms and their relationship to therapeutic strategies. Histopathology reveals surfactant disruption, epithelial perturbation and sepsis, either as initiating factors or as secondary complications, which in turn increase the expression of cytokines that sequester and activate inflammatory cells, most notably, neutrophils. Concomitant release of reactive oxygen and nitrogen species subsequently modulates endothelial function. Together these events orchestrate the principal clinical manifestations of the syndrome, pulmonary edema and atelectasis. To better understand the gene-environmental interactions controlling this complex process, we examined the relative sensitivity of inbred mouse strains to acute lung injury induced by ozone, ultrafine PTFE, or fine particulate NiSO4 (0.2 microm MMAD, 15-150 microg/m3). Measuring survival time, protein and neutrophils in bronchoalveolar lavage, lung wet: dry weight, and histology, we found that these responses varied between inbred mouse strains, and susceptibility is heritable. To assess the molecular progression of NiSO4-induced acute lung injury, temporal relationships of 8734 genes and expressed sequence tags were assessed by cDNA microarray analysis. Clustering of co-regulated genes (displaying similar temporal expression patterns) revealed the altered expression of relatively few genes. Enhanced expression occurred mainly in genes associated with oxidative stress, anti proteolytic function, and repair of the extracellular matrix. Concomitantly, surfactant proteins and Clara cell secretory protein mRNA expression decreased. Genome wide analysis of 307 mice generated from the backcross of resistant B6xA F1 with susceptible A strain identified significant linkage to a region on chromosome 6 (proposed as Aliq4) and suggestive linkages on chromosomes 1, 8, and 12. Combining of these QTLs with two additional possible modifying loci (chromosome 9 and 16) accounted for the difference in survival time noted in the A and B6 parental strains. Combining these findings with those of the microarray analysis has enabled prioritization of candidate genes. These candidates, in turn, can be directed to the lung epithelium in transgenic mice or abated in inducible and constitutive gene-targeted mice. Initial results are encouraging and suggest that several of these mice vary in their susceptibility to oxidant induced lung injury. Thus, these combined approaches have led to new insights into functional genomics of lung injury and diseases. PMID- 11764986 TI - Mitochondrial-derived oxidants and quartz activation of chemokine gene expression. AB - Macrophage inflammatory protein 2 (MIP-2) is a chemotactic cytokine which mediates neutrophil recruitment in the lung and other tissues. Pneumotoxic particles such as quartz increase MIP-2 expression in rat lung and rat alveolar type II epithelial cells. Deletion mutant analysis of the rat MIP-2 promoter demonstrated quartz-induction depended on a single NFkappaB consensus binding site. Quartz activation of NFkappaB and MIP-2 gene expression in RLE-6TN cells was inhibited by anti-oxidants suggesting the responses were dependent on oxidative stress. Consistent with anti-oxidant effects, quartz was demonstrated to increase RLE-6TN cell production of hydrogen peroxide. Rotenone treatment of RLE-6TN cells attenuated hydrogen peroxide production, NFkappaB activation and MIP-2 gene expression induced by quartz indicating that mitochondria-derived oxidants were contributing to these responses. Collectively, these findings indicate that quartz and crocidolite induction of MIP-2 gene expression in rat alveolar type II cells results from stimulation of an intracellular signaling pathway involving increased generation of hydrogen peroxide by mitochondria and subsequent activation of NFkappaB. PMID- 11764987 TI - Quinoids as reactive intermediates in estrogen carcinogenesis. PMID- 11764988 TI - Assessing underlying mechanisms of quinoid-induced hematopoietic cell toxicity. PMID- 11764989 TI - Structure of the malondialdehyde deoxyguanosine adduct M1G when placed opposite a two-base deletion in the (CpG)3 frameshift hotspot of the Salmonella typhimurium hisD3052 gene. AB - Malondialdehyde (MDA) is a toxic and mutagenic metabolite produced by lipid peroxidation, and prostaglandin biosynthesis. MDA induces frameshift mutations in tester strains of Salmonella typhimurium. It reacts with DNA, and at physiological pH the major adduct is a pyrimidopurinone formed by reaction with guanine: M1G [3-(2'-deoxy-beta-D-erythropentofuranosyl)pyrimido[1,2-alpha]-purin 10(3H)-one]. When site-specifically incorporated into a duplex oligodeoxynucleotide containing a frameshift-prone (CG)3 repeat derived from the Salmonella typhimurium hisd3052 gene, spontaneous opening of M1G to the N2-(3-oxo 1-propenyl)-dG species occurred. In this work d(ATCGCMCGGCATG), (M=M1G) was annealed to d(CATGCCGCGAT) to model the putative strand slippage intermediate which would precede a two base deletion in the (CG)3 iterated repeat. 1H NMR studies indicate that in contrast to the duplex DNA structure, M1G remains intact. A single bulge conformation exists. M1G and its 3'-neighbor cytosine are unpaired. The M1G is intrahelical and stacked, whereas the unpaired cytosine is poorly stacked and appears to be extrahelical. PMID- 11764990 TI - A sensitive procedure for the determination of protein bound 3,4-dihydroxyphenyl alanine as a marker for posttranslational protein hydroxylation in human frontal cortex, liver, and red blood cells. PMID- 11764991 TI - Reactive metabolite screen for reducing candidate attrition in drug discovery. PMID- 11764992 TI - Metabolism of R,S enantiomers of 3-phenylamino-1,2-propanediol, a compound associated with the toxic oil syndrome, in C57BL/6- and A/J-strain mice. AB - PAP, a very polar substance, is highly metabolized in mice and excreted principally in urine in the form of the 2-hydroxy-3-phenylaminopropanoic acid of each enantiomer. Thus, the major route of PAP elimination in these strains is alkyl chain oxidation. In particular, S-PAP is eliminated principally in the form of that metabolite, whereas R-PAP enantiomer showed further oxidized species at the aromatic ring and alkyl chain, yielding potential decarboxylated compounds and iminoquinones. All these metabolites may have toxicologic implications. On the other hand, OOPAP intestinal hydrolysis in favour of one PAP enantiomer might be expected since lipases show chiral hydrolysis (unpublished data, manuscript in preparation). In this respect, enantiomeric distribution and metabolic differences should be taken into account in the toxicokinetics of these compounds and their potential association with Toxic Oil Syndrome symptoms. PMID- 11764993 TI - Bioactivation of toxicants by cytochrome p450-mediated dehydrogenation mechanisms. PMID- 11764994 TI - Cytochrome P450-catalysed irreversible binding examined in precision-cut adrenal slice culture. PMID- 11764995 TI - Elevation of glutathione levels by coffee components and its potential mechanisms. PMID- 11764996 TI - Inhibition of carcinogenesis and toxicity by dietary constituents. PMID- 11764997 TI - Modelling the responses to biological reactive intermediates: establishing the borderlines of risk. PMID- 11764998 TI - Interindividual differences in response to chemoprotection against aflatoxin induced hepatocarcinogenesis: implications for human biotransformation enzyme polymorphisms. AB - It is now evident that most, if not all, of the remarkable species differences in susceptibility to AFB hepatocarcinogenesis is due in large part, if not exclusively, to differences in biotransformation. Certainly the relative rate of oxidative formation of the proximate carcinogen, AFB-8,9-exo-epoxide, is an important determinant of species and interindividual differences in susceptibility to AFB. However, mice produce relatively large amounts of exo AFBO, yet are highly resistant to AFB-hepatocarcinogenesis because they express a particular form of GST with remarkably high catalytic activity toward the exo epoxide of AFB. Rats, which are highly susceptible to AFB hepatocarcinogenesis,can be made resistant through dietary induction of an orthologous form of GST that is normally expressed in only very small amounts. Based on these findings in laboratory animal models, there is great interest in identifying chemicals and/or specific dietary constituents that could offer protection against AFB-hepatocarcinogenesis to humans. Current experimental strategies have focused on the antiparasitic drug, oltipraz, which induces protection in rats and has also shown some promise in humans. The mechanism of protection in rats appears to be via induction of an alpha class GST with high catalytic activity toward AFBO (rGSTA5-5). vet human alpha class GST proteins that are constitutively expressed in the liver (hGSTA1 and hGSTA2) have little, if any activity toward AFBO. Rather, it appears that mu class GSTs may be responsible for the very low, but potentially significant, detoxification activity toward AFBO. Oltipraz and certain dietary constituents may induce mu class GSTs in human liver, and this could afford some protection against the genotoxic effects of AFBO. However, it also appears that oltipraz, and perhaps certain dietary constituents, act as competitive inhibitors of human CYP1A2. As CYP1A2 appears to mediate most of the activation of AFB to exo-AFBO in human liver at low dietary concentrations of AFB encountered in the human diet, much of the putative protective effects of oltipraz could be mediated via inhibition of CYP1A2 rather than induction of GSTs. There is now evidence that human microsomal epoxide hydrolase (mEH) could play a role in protecting human DNA from the genotoxic effects of AFB, although the importance of this detoxification pathway, relative to mu class GSTs, remains to be elucidated. Oltipraz is an effective inducer of mEH in rats (Lamb Franklin, 2000), and thus induction of this pathway in humans could also potentially contribute to the protective effects of this drug toward AFB genotoxicity. Because the dihydrodiol of AFB may contribute indirectly to the carcinogenic effects of AFB via protein adduction and subsequent hepatotoxicity, the recently characterized human aflatoxin aldehyde reductase (AFAR) may also offer some protection against AFB-induced carcinogenicity in humans. Current and future dietary and/or chemointervention strategies aimed at reducing the carcinogenic effects of AFB in humans should consider all of the possible mechanistic approaches for modifying AFB-induced genotoxicity. PMID- 11764999 TI - Sequestration of biological reactive intermediates by trapping as covalent enzyme intermediate complex. AB - One important class of biological reactive intermediates arising in the course of human xenobiotic metabolism are arene and alkene oxides. The major safeguard against the potential genotoxic effects of these compounds is the microsomal epoxide hydrolase (mEH). This enzyme has a broad substrate specificity but--on the first sight--seems to be inadequately suited for this protection task due to its low turnover number with most of its substrates. The recent progress in the understanding of the mechanism of enzymatic epoxide hydrolysis has shed new light on this apparent dilemma: Epoxide hydrolases convert their substrates via the intermediate formation of a covalent enzyme-substrate complex, and it has been shown that the formation of the intermediate proceeds by orders of magnitudes faster than the subsequent hydrolysis, i.e. the formation of the terminal product. Thus, the enzyme acts like a molecular sponge by binding and inactivating the dangerous metabolite very fast while the subsequent product release is considerably slower, and quantification of the latter heavily underestimates the speed of detoxification. Usually, the slow enzyme regeneration does not pose a problem, since the mEH is highly abundant in human liver, the organ with the highest capacity to metabolically generate epoxides. Computer simulation provides evidence that the high amount of mEH enzyme is crucial for the control of the steady-state level of a substrate epoxide and can keep it extremely low. Once the mEH is titrated out under conditions of extraordinarily high epoxide concentration, the epoxide steady-state level steeply rises, leading to a sudden burst of the genotoxic effect. This prediction of the computer simulation is in perfect agreement with our experimental work. V79 Chinese Hamster cells that we have genetically engineered to express human mEH at about the same level as that observed in human liver are well protected from any measurable genotoxic effect of the model compound styrene oxide (STO) up to an apparent threshold level of 100 microM in the cell culture medium. In V79 cells that do not express mEH, STO triggers the formation of DNA strand breaks in a dose-dependent manner with no apparent threshold. Above 100 microM, the genotoxic effect of STO in the mEH-expressing cell line parallels the one in the parental cell line. PMID- 11765000 TI - Chemoprotection and interindividual differences in response to biological reactive intermediates. PMID- 11765001 TI - Oxidative stress, glucose-6-phosphate dehydrogenase and the red cell. AB - As discussed above, the process by which normal senescent red cells are selected for removal from the circulation is the subject of much ongoing research and is not yet well understood. This in turn creates a problem for studies on the enhanced removal that occurs in xenobiotic-induced hemolytic states; specifically, whether the enhanced removal should be considered as an increase in rate of the normal sequestration mechanism or as an unrelated process, in part or in whole. This difficulty bears directly on the interpretation of much of the mechanistic hemolytic literature. Because of its dual in vivo and in vitro hemolytic capability, and because of its capacity to induce frank lysis in the incubation mixture, phenylhydrazine has been used extensively as a model compound for mechanistic studies. These data have contributed heavily to our current concepts of how chemicals induce damage in the red cell. The comparison studies presented above cast doubt on the relevance of many of these phenylhydrazine studies for the in vivo hemolytic response. Phenylhydrazine, like divicine and DDS-NOH, shows an overwhelming predominance of uptake into the spleen, as distinct from removal by the RES system in general, as evidenced by relatively low liver uptake. This suggests strongly that damaged cells are removed intact by the spleen and do not lyse or fragment in the general circulation, at least to any significant extent. The studies with DDS-NOH indicate that neither Heinz body formation nor lipid peroxidation per se are essential steps in the process by which damaged red cells are removed from the circulation in the rat. It is not yet clear whether this lack of obligatory involvement of Heinz bodies and lipid peroxidation is peculiar to the arylhydroxylamine-induced hemolytic state or whether it will prove to be of general applicability. On the other hand, cysteamine failed to reverse the hemolytic damage caused by phenylhydrazine. Since cysteamine "rescued" DDS-NOH treated cells under the same experimental conditions, this observation raises the possibility that protein-thiol oxidation per se is also not an obligatory step in the sequence of events leading to premature sequestration. Clearly, the ratio of lipid to protein oxidation is markedly different in these three examples of hemotoxic compounds. DDS-NOH showed high protein oxidation with no discernible lipid oxidation, divicine showed both high protein and high lipid oxidation, and phenylhydrazine showed high lipid and low protein oxidation. While the significance of these markedly different patterns of injury is far from clear, it seems reasonable to conclude that there is more than one way by which chemicals damage the red cell. It is intriguing that these apparently different chemical insults within the red cell result in a common "message" on the outside of the cell, such that the cell appears as "prematurely" aged. Although the pattern of injury inside the cell may be significantly different, the process by which the three hemotoxic compounds enhance uptake by splenic macrophages may remain the same. That is, there may be a variety of insults sustained within the red cell that lead by different pathways to similar "recognition-specific" changes on the external surface of the red cell. Clearly, comparison of the effects of the three hemotoxic compounds will shed light on both the hemolytic process and on normal red cell sequestration mechanisms. PMID- 11765002 TI - Hepatocarcinogenesis in the context of strain differences in energy metabolism between inbred strains of mice (C57BL/6J and C3H/He). PMID- 11765003 TI - Characterization of hOGG1 promoter structure, expression during cell cycle and overexpression in mammalian cells. PMID- 11765004 TI - hOGG1 gene alterations in human clear cell carcinomas of the kidney: effect of single mutations in hOGG1 gene on substrate specificity of the hOGG1 protein. PMID- 11765006 TI - Determination of nucleotide excision repair capacity of liver cells in vivo and in vitro by a cell-free assay. PMID- 11765005 TI - Proinflammatory cytokines mRNA expression in dependence of suppressive epitope of retroviral transmembrane p15E peptide activation at multiple sclerosis patients. PMID- 11765007 TI - Dietary induction of phase II enzymes: a promising strategy for protection against DNA-reactive intermediates in man? PMID- 11765008 TI - New aspects of DNA adduct formation by the carcinogens crotonaldehyde and acetaldehyde. PMID- 11765009 TI - Concurrent flavin-containing monooxygenase down regulation and cytochrome P450 induction by dietary indoles in the rat: implication for drug-drug interactions. PMID- 11765010 TI - Reactive intermediates in biological systems: what have we learned and where are we going? PMID- 11765011 TI - The role of toxicological science in risk assessment and risk management. PMID- 11765012 TI - Covalent binding of chemical residues: health impact. PMID- 11765013 TI - Identification of hepatic protein targets of the reactive metabolites of the non hepatotoxic regioisomer of acetaminophen, 3'-hydroxyacetanilide, in the mouse in vivo using two-dimensional gel electrophoresis and mass spectrometry. PMID- 11765014 TI - Exocyclic DNA adducts as secondary markers for oxidative stress: applications in human cancer etiology and risk assessment. PMID- 11765015 TI - Dose dependent induction of DNA adducts, gene mutations, and cell proliferation by the antiandrogenic drug cyproterone acetate in rat liver. AB - 1. CPA does not only induce the formation of DNA adducts but also of mutations in female rat liver. 2. The mutation frequency exhibited a characteristic time course. Within a period of 3 days post administration, a tremendous increase was noted, which remained at a high level until 2 weeks post exposure. Thereafter, most mutation-carrying cells were eliminated within a period of 2 weeks leaving a cell population remaining at a constant level for another 4 weeks. Thus, the length of the observation period post exposure, i. e. the manifestation time, seems to be a critical factor for the strength of the mutagenic response. The highest as observed between 1 and 2 weeks post exposure. Correspondingly, the dose response curve recorded 2 weeks post exposure showed a higher mutagenic response than the curve after 6 weeks of exposure recorded previously. 3. When CPA-induced mutations were recorded as a function of the dose, mutation frequencies at the lower dose range were found that did not differ from those of controls. The non-effective dose recorded 2 weeks post exposure was much lower than that recorded after 6 weeks of exposure indicating that it is a function of the manifestation time. Since DNA adducts were formed in high amounts at the non effective doses, we assume that the mitogenic activity required for the conversion of DNA adducts into mutations was not sufficiently strong. The liver of adult animals exhibits a very low endogeneous proliferation rate, which is not likely to contribute significantly to the expression of mutations. We conclude that it is the mitogenic activity of CPA itself, which stimulates the expression of mutations. PMID- 11765016 TI - Dose-dependent differences in the profile of mutations induced by carcinogenic (R,S,S,R) bay- and fjord-region diol epoxides of polycyclic aromatic hydrocarbons. AB - Chinese hamster V79 cells were exposed to a high or low concentration of the highly carcinogenic (R,S,S,R) or the less active (S,R,R,S) bay- or fjord-region diol epoxides of benzo[a]pyrene, benzo[c]phenanthrene or dibenz[c,h]acridine. Independent 8-azaguanine-resistant clones were isolated, and base substitutions at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus were determined. For the three (R,S,S,R) diol epoxides studied, the proportion of mutations at AT base pairs increased as the concentration of diol epoxide decreased. Concentration-dependent differences in the mutational profile were not observed, however, for the three (S,R,R,S) diol epoxides. In studies, with V-H1 cells (a DNA repair deficient variant of V79 cells), a concentration-dependent difference in the profile of mutations for the (R,S,S,R) diol epoxide of benzo[a]pyrene was not observed. These results suggest that concentration dependent differences in the mutational profile are dependent on an intact DNA repair system. In additional studies, we initiated mouse skin with a high or low dose of benzo[a]pyrene and promoted the mice for 26 weeks with 12-O tetradecanoylphorbol-13-acetate. Papillomas were examined for mutations in the c Ha-ras proto-oncogene. Dose-dependent differences in the profile of c-Ha-ras mutations in the tumors were observed. In summary, (i) dose-dependent differences in mutational profiles at the hprt locus were observed in Chinese hamster V79 cells treated with several highly mutagenic and carcinogenic (R,S,S,R) bay- or fjord-region diol epoxides but not with their less active (S,R,R,S) diol epoxide enantiomers, (ii) a dose-dependent difference in the mutational profile was not observed for the (R,S,S,R) diol epoxide of benzo[a]pyrene in a DNA-repair defective V79 cell line, and (iii) a dose-dependent difference in the mutational profile in the c-Ha-ras proto-oncogene was observed in tumors from mice treated with a high or low dose of benzo[a]pyrene. PMID- 11765017 TI - Nucleic acid microarray technology for toxicology: promise and practicalities. AB - Much ongoing research in toxicology focuses on a hypothesis-driven mechanism of action approach aimed at understanding the molecular events mediating the actions of the chemicals of interest. Using this approach, investigators develop hypotheses based on observations, which may be derived from a host of resources but most frequently have been made within their own laboratories, or uncovered by others and reported in the scientific literature. Although the bulk of current understanding ofbiochemical toxicology emerged using studies based on observations derived in this way, this process, which is essentially based on existing information, may often limit the expansion knowledge. More simply expressed, one only finds that which one seeks. Without a clear understanding of the processes targeted by a specific toxin the problem of making observations that globally and accurately reflect the events mediating pathology which have been induced by the toxic agent is challenging. Recently, the development of high throughput technologies for biochemical analysis of gene expression has led to innovative approaches in addressing the problem of making broad-based observations that more accurately reflect the entire spectrum of molecular lesions induced by specific toxins. These strategies include the use of new techniques in analysis of gene expression to convey information on alterations in mRNA levels, one of the earliest cellular signs initiated in response to a potential toxin. Prior to this time studies on toxicant-induced altered gene expression were limited to single, or small numbers of identified genes chosen by an investigator who reasoned, based on an existing observations, that levels of the proteins encoded by these genes were likely to be altered during toxic injury. Now, using cDNA or oligonucleotide genome-wide arrays, toxin-induced alterations in gene expression of thousands of genes can be examined simultaneously. Using these tools, molecular toxicologists can for the first time employ reasoned strategies to make observations, and then formulate hypotheses based on these observations. PMID- 11765018 TI - Use of covalent binding in risk assessment. AB - Risk characterization comprises hazard identification describing the intrinsic toxic potential of a chemical, toxicokinetics, as well as the toxic mechanisms, information about dose response and exposure assessment. Compounds that induce reversible effects, which are repaired during and after exposure, are considered thresholded and allow definition of a NOEL. If damage is not repaired, the effect persists and accumulates upon repeated exposure. In such cases a NOEL cannot be determined. Biological reactive intermediates of chemicals have the potential to bind covalently to cellular macromolecules like proteins and DNA. Such interaction is not repaired completely and may persist. Thus, data on covalent binding (CB) are of qualitative and quantitative significance in the risk assessment process. Qualitatively, CB, especially with DNA and in correlation with this to proteins, is indicative for an irreversible and non-thresholded mutagenic and carcinogenic effect. Absence or presence of CB assists to differentiate between primarily genotoxic and thresholded non-genotoxic carcinogens. Quantitatively, CB is used to understand internal exposure and target dose, which is a prerequisite for species-species extrapolation, and to justify extrapolation from high dose to low dose. The reactive intermediates of ethylene, propylene and styrene have been determined in rodents and humans and modeled to predict dose responses of internal exposure. It is described in this communication that such information, together with other parameters like cell proliferation as a result of cytotoxicity, is the basis for quantitative risk assessment of human exposure to these compounds. PMID- 11765019 TI - Mechanisms of ovotoxicity induced by environmental chemicals: 4-vinylcyclohexene diepoxide as a model chemical. PMID- 11765020 TI - Mutagenicity and carcinogenicity of biological reactive intermediate's derived from a "non-genotoxic" carcinogen. PMID- 11765021 TI - Reactive metabolites of 1,3-butadiene: DNA and hemoglobin adduct formation and potential roles in carcinogenicity. PMID- 11765022 TI - Mechanistic studies on the use of 2H- and 13C-analogues as internal standards in selected ion monitoring GC-MS quantitative determination--butalbital example. AB - As a part of our study on the use of isotopic analogues as the internal standard (IS) for the quantitation of drug analytes, this article reports on the performance characteristics of 2H5-butalbital and 13C4-butalbital with particular focus on (1) determining and comparing the effectiveness of the 2H- and 13C analogues in serving as the ISs for quantitation; (2) understanding the "cross contribution" phenomenon underlying the effectiveness of selected ion pairs used for quantitation purpose; and (3) examining whether the same characteristics, observed in our preliminary report for the secobarbital/2H5-secobarbital/13C4 secobarbital system, also exist in the butalbital/2H5-butalbital/13C4-butalbital system. Adapting similar procedures applied to our previous study on the secobarbital system, we observed that (1) both labeled analogues (13C4-butalbital and 2H5-butalbital) cause more significant cross-contributions to ions designated for butalbital than butalbital to the labeled analogues; (2) compared to 2H5 butalbital, 13C4-butalbital appears to cause less cross-contributions to ions designated for butalbital; (3) cross-contribution between the following ion pairs are minimal: m/z 200/196, 199/195, 185/181 (13C4-butalbital as the IS) and m/z 201/196 (2H5-butalbital as the IS). It is also concluded that the butalbital/2H5 butalbital system exhibits the same concentration dependency phenomenon observed in the secobarbital/ 2H5-secobarbital system, that is, ratios of ion pairs designated for these two isotopic analogues (resulting from routine gas chromatography-mass spectrometry protocol) increase as their concentrations are diluted. (In parallel with the secobarbital/13C4-secobarbital system, the butalbital/13C4-butalbital system does not exhibit this phenomenon.) PMID- 11765023 TI - Performance of five non-instrumented urine drug-testing devices with challenging near-cutoff specimens. AB - A comparison of five non-instrumented urine drug-testing devices was performed using a challenging clinical specimen set with drug concentrations close to the immunoassay screening cutoffs. The five devices were Syva RapidTest d.a.u. 8, Syva RapidCup d.a.u. 5, Roche TesTcup 5, Biosite Triage, and Casco-Nerl microLINE Drug Screen Card. Sixty clinical specimens for each of the five SAMHSA-specified drug categories were tested by both a scientist and a non-scientist with each result independently read by both. All specimens were also tested on a benchtop automated immunoassay analyzer (Syva ETS using Emit d.a.u. reagents) for comparison and by gas chromatography-mass spectrometry (GC-MS). The non instrumented devices demonstrated an overall accuracy of 70% (66-74%), based on standard GC-MS confirmation cutoffs, comparable to the Syva ETS analyzer (80%). There was also little difference in overall accuracy between the scientist (71%) and non-scientist (69%), although the non-scientist reported 10 false-positive results (0.7% of 1490 total results or 3.8% of 260 results for drug-free specimens), and the scientist reported only 1 false-positive result (0.07% of 1490 total results or 0.38% of 260 results for drug-free specimens). When device performance was assessed according to drug presence/absence criteria, accuracy generally improved with all devices demonstrating extremely high positive predictive values (0.98-1). PMID- 11765024 TI - Determination of glufosinate ammonium and its metabolite, 3 methylphosphinicopropionic acid, in human serum by gas chromatography-mass spectrometry following mixed-mode solid-phase extraction and t-BDMS derivatization. AB - A method for the analysis of glufosinate ammonium (GLUF) and its metabolite 3 methylphosphinicopropionic acid (MPPA) in human serum by gas chromatography-mass spectrometry (GC-MS) was developed. Employing a mixed-mode cartridge with both anion exchange action and weak nonpolar interaction, we extracted GLUF and MPPA from the serum and carried out GC-MS analysis of their tert-butyldimethylsilyl derivatives. The detection limits of GLUF and MPPA were 10 pg and 1 pg, respectively. Full mass spectra of 100 pg GLUF and of 10 pg MPPA were easily obtainable. The recovery rate of 90.0+/-11.9% (or better) when the serum concentrations of GLUF and MPPA were 10-0.1 microg/mL. Results of 23 serum samples, from patients with GLUF poisoning, measured by this method correlate well with those derived from the conventional high-performance liquid chromatography method (r = 0.996). The developed GC-MS method is likely to become a useful analytical technique in clinical settings. PMID- 11765025 TI - Human nutritional supplements in the horse. Dehydroepiandrosterone versus androstenedione: comparative effects on the androgen profile and consequences for doping analysis. AB - Dehydroepiandrosterone (DHEA) and androstenedione are weak androgens, which need conversion to more potent testosterone in order to enhance anabolic action. Consequences of oral dosing at 1 mg/kg on the urinary and plasma androgen profile of mare and gelding have been evaluated with an analytical method involving conjugate fractionation and selective hydrolysis, group separation, and quantitation by gas chromatography-mass spectrometry with selected ion monitoring of trimethylsilyl ethers. Peak levels of testosterone total conjugates in urine (range 300-6000 microg/L) were attained a few hours after dosing. Renal clearance was fast, so the testosterone detection period lasted only 20 to 33 h, the longest time being generated by androstenedione. The urinary testosterone/epitestosterone ratio for detection of exogenous testosterone in the mare was inoperative after DHEA administration because there was a concomitant increase of epitestosterone, which thereby acted as a masking agent. Androstanediols and androstenediols, as well as some 17-ketosteroids, were additional markers. A transient increase of circulating free testosterone has been evidenced, and this would support possible anabolic/androgenic action by supplementation with DHEA and androstenedione along the oral route. PMID- 11765026 TI - Evaluating the impact of hemp food consumption on workplace drug tests. AB - Foods containing seeds or oil of the hemp plant (Cannabis sativa L.) are increasingly found in retail stores in the U.S. The presence of delta9 tetrahydrocannabinol (THC) in these foods has raised concern over their impact on the results of workplace drug tests for marijuana. Previous studies have shown that eating hemp foods can cause screening and confirmed positive results in urine specimens. This study evaluated the impact of extended daily ingestion of THC via hemp oil on urine levels of its metabolite 11-nor-9-carboxy-delta9 tetrahydrocannabinol (THC-COOH) for four distinct daily THC doses. Doses were representative of THC levels now commonly found in hemp seed products and a range of conceivable daily consumption rates. Fifteen THC-naive adults ingested, over four successive 10-day periods, single daily THC doses ranging from 0.09 to 0.6 mg. Subjects self-administered THC in 15-mL aliquots (20 mL for the 0.6-mg dose) of four different blends of hemp and canola oils. Urine specimens were collected prior to the first ingestion of oil, on days 9 and 10 of each of the four study periods, and 1 and 3 days after the last ingestion. All specimens were screened for cannabinoids by radioimmunoassay (Immunalysis Direct RIA Kit), confirmed for THC-COOH by gas chromatography-mass spectrometry (GC-MS), and analyzed for creatinine to identify dilute specimens. None of the subjects who ingested daily doses of 0.45 mg of THC screened positive at the 50-ng/mL cutoff. At a daily THC dose of 0.6 mg, one specimen screened positive. The highest THC-COOH level found by GC-MS in any of the specimens was 5.2 ng/mL, well below the 15-ng/mL confirmation cutoff used in federal drug testing programs. A THC intake of 0.6 mg/day is equivalent to the consumption of approximately 125 mL of hemp oil containing 5 microg/g of THC or 300 g of hulled seeds at 2 microg/g. These THC concentrations are now typical in Canadian hemp seed products. Based on our findings, these concentrations appear to be sufficiently low to prevent confirmed positives from the extended and extensive consumption of hemp foods. PMID- 11765027 TI - Serum and urine concentrations of flunitrazepam and metabolites, after a single oral dose, by immunoassay and GC-MS. AB - A clinical study was conducted to assess the ability of commercially available immunoassays to detect flunitrazepam (FNP) in plasma and urine samples and to compare the results with those obtained by gas chromatography-mass spectrometry (GC-MS). The clinical study consisted of four individuals (two male and two female) who had taken a single 2-mg dose of FNP. Serum was collected over a 48-h period and urine was collected over a 72-h period. The serum and urine samples were analyzed by the COBAS INTEGRA Serum Benzodiazepines assay (SBENZ), the TDx serum and urine Benzodiazepines assay, and GC-MS. The GC-MS procedure was developed for analysis of FNP and metabolites in plasma and urine using an acid hydrolysis step resulting in the formation of specific benzophenones corresponding to FNP and its metabolites. The relative sensitivities of the assays for the detection of FNP and metabolites in serum and urine were GC-MS > SBENZ > TDx. The immunoassay results for serum samples showed peak concentrations of FNP metabolites at 8 h after FNP ingestion for three individuals and at about 1 h for the fourth individual. The GC-MS, SBENZ, and TDx urine immunoassays detected drug above the stated limit of detection (LOD) in 44, 41, and 35 serial FNP urine samples, respectively. FNP metabolites were detected in urine samples with all three assays for up to 72 h after a 2-mg dose. The improved detection rate with the SBENZ assay as compared to the TDx assay is likely explained by its higher cross-reactivity with the major metabolite, 7-amino-flunitrazepam (7-amino FNP), and its lower LOD. PMID- 11765028 TI - Fatal 4-MTA intoxication: development of a liquid chromatographic-tandem mass spectrometric assay for multiple matrices. AB - The case history and toxicological findings of an overdose fatality involving 4 methylthioamphetamine (4-MTA) and 3,4-methylenedioxymethamphetamine (MDMA) are reported along with a description of the analytical method. Detection and quantitation of 4-MTA and MDMA were performed by liquid chromatography-tandem mass spectrometry using phentermine as internal standard. Application of this technique to a variety of matrices allowed an insight in the distribution of 4 MTA. Several blood samples including femoral vein blood (5.23 mg/L), urine (95.5 mg/L), vitreous humor (1.31 mg/L), bile (36.4 mg/L), and numerous tissue samples such as liver (30.8 mg/kg), spleen (4.10 mg/kg), and frontal lobe (31.7 mg/kg) were assayed. These values indicated that 4-MTA could be identified as the cause of this fatality, whereas the concentrations of MDMA, also described, are less important because the concentrations found are lower. This case reports, for the first time, an extensive toxicological analysis of 4-MTA, by which the data presented may shed some light on the distribution of 4-MTA. PMID- 11765029 TI - Analysis of the lidocaine metabolite 2,6-dimethylaniline in bovine and human milk. AB - 2,6-Dimethylaniline (2,6-xylidine; 2,6-DMA) is a nasal carcinogen in rats. Humans may be exposed to this compound via several routes: 2,6-DMA is found in cigarette smoke; it is a pharmacologically inactive metabolite of some drugs (e.g., the local anesthetic lidocaine) and pesticides (e.g., metalaxyl); and it is an impurity in technical grade metalaxyl. The potential transfer of 2,6-DMA from mother to nursing infant via milk is of toxicological concern. Solid-phase microextraction with separation and detection using gas chromatography-mass spectrometry was optimized and used for the analysis of 2,6-DMA in milk. 2,6-DMA d9 was synthesized and used for quantitation by the isotope ratio method. At a concentration of 5 ppb 2,6-DMA, the method detection limit was 0.20 ppb, and the relative standard deviation was 3.6%. Samples of milk were obtained from bovines administered lidocaine (2.9-3.9 mg/kg) during surgery. A breast milk sample was also obtained from a human donor who received 36 mg lidocaine during dental work. 2,6-DMA was present at levels ranging from 14.5 to 66.0 ppb in bovine milk and was detected at 1.6 ppb in the human milk sample. Our results demonstrate that 2,6-DMA, formed by the metabolism of lidocaine, is transferable to bovine and human milk. PMID- 11765030 TI - A fatal case of moclobemide-citalopram intoxication. PMID- 11765031 TI - 2-Alkyloxyalkylthiohypoxanthines as new potent inhibitors of xanthine oxidase. AB - The title compounds were prepared and tested as xanthine oxidase (XO) inhibitors. Results evidenced that potency was related to the position of the oxygen atom in the 2-linear chain and that it grew with distance from the sulfur atom until it became equipotent to 2-n-hexylthiohypoxanthine. Enzymatic oxidation on C(2) occurred in the 8-alkylthiohypoxanthines. On the contrary, oxidation on C(8) did not occur in the 2-alkythioderivatives, demonstrating that the chain forced these molecules to form a complex with molybdenum(VI) involving only the N(3) and N(9) nitrogen atoms. PMID- 11765032 TI - Synthesis and antiviral assays of some benzimidazole nucleosides and acyclonucleosides. AB - Some benzimidazole nucleosides and acyclonucleosides were synthesized and tested in vitro as antiviral agents. None of them showed significant activity. Replacement of the benzenesulphonyl group at N-1 with the ribofuranosyl moiety or with the acyclovir side-chain was deleterious. PMID- 11765033 TI - Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2 a]benzimidazol-1-one derivatives. AB - A number of novel 1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives were prepared and their anticonvulsant properties evaluated. The new synthesized compounds proved to possess anticonvulsant effects depending on the nature of substituents at C-6, C-2, and C-3a positions of the polycyclic system. In particular, the 6 chloro-3a-(p-tolyl)-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivative (22) displayed potency fivefold higher than unsubstituted compound (13). PMID- 11765035 TI - Synthesis and analytical evaluation by voltammetric studies of some new indole-3 propionamide derivatives. AB - Some biologically important and melatonin-related indole-3-propionamide derivatives were synthesized. The compounds synthesized were analyzed and characterized first by NMR and mass spectrometry and then investigated by analytical voltammetric techniques. Based on this study a simple, rapid and sensitive voltammetric method was developed for the determination of the indole derivatives that are readily oxidized at the carbon-based electrodes. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode. The characteristics of the corresponding electrode reaction were discussed. PMID- 11765034 TI - New 5-substituted-1-(2-hydroxybenzoyl)-benzotriazoles, potassium channel activators. IV. AB - This paper reports the synthesis of a series of new 5-substituted-1-(2 hydroxybenzoyl)-benzotriazoles, which have been tested for their activity as possible activators of potassium channels. In rat aortic rings, the 'opened' derivatives 1a-f, intermediates of synthesis, showed vasorelaxing properties, with appreciable values of potency. However, the most remarkable effects were recorded for the 2-hydroxybenzoylbenzotriazoles 3a-f, which showed full vasorelaxing efficacy and high potency values. The introduction of a 2 hydroxybenzyl substituent in the 1 position of the benzotriazole ring (compound 7) strongly decreased the activity, showing the importance of the electron acceptor carbonyl function. The best compound, 3b, was further investigated, in order to evaluate the possible mechanism of action involved in the vasodilator activity. In the vascular model, different potassium channel blockers inhibited the effects of the compound, and an increase of the levels of membrane depolarisation induced a significant reduction of the recorded responses. Compound 3b was also tested in a model of isolated rat heart, retroperfused through the aorta and submitted to a global ischemia/reperfusion cycle. In such an experimental condition, 3b showed an interesting cardioprotective activity. All the above observations are in agreement with the hypothesis of a mechanism linked to the activation of potassium channels. PMID- 11765037 TI - Synthesis and activity on human neutrophil functions of fMLF-OMe analogs containing alkyl spacers at the central position. AB - We report here the synthesis and activity of new analogs of the N-formyl and N tert-butyloxycarbonyl (Boc) derivatives of the tripeptide Met-Leu-Phe-OMe containing an achiral omega-amino acid residue replacing the hydrophobic central leucine. The tripeptides HCO-Met-NH-(CH2)n-CO-Phe-OMe and Boc-Met-NH-(CH2)n-CO Phe-OMe (n = 3-5) containing the central homomorphic residue of 5-aminopentanoic acid (delta-aminovaleric acid; delta-Ava; n = 4) and the two non-homomorphic residues of 4-aminobutanoic acid (gamma-aminobutyric acid; gamma-Abu; n = 3) and 6-aminohexanoic acid (epsilon-aminocaproic acid; epsilon-Aca; n = 5) have been examined. The activity as agonists and antagonists in chemotaxis, lysozyme release, and superoxide anion production of the new analogs has been determined. The N-Boc derivatives 2a and 2b, incorporating the gamma-Abu and the delta-Ava residues, show good and selective antagonist activity on superoxide anion production. PMID- 11765036 TI - Some structural changes on triazolyl-benzotriazoles and triazolyl benzimidazolones as potential potassium channel activators. III. AB - This paper reports the synthesis and pharmacological evaluation of some compounds, obtained by structural modifications of 1,2,3-triazolyl-benzotriazoles and 1,2,3-triazolyl-benzimidazolones, which had shown activity as potential activators of the big-conductance calcium-activated potassium channels (BK(Ca)). Changes have concerned the introduction of a hinderer substituent in the 5 position of the benzimidazolone (4a, b) and benzotriazole (5a, b) rings, opening of the benzimidazolone ring (7) and substitution of the 1,2,3-triazole ring with a 2-hydroxyphenyl ring (10). Furthermore a series of 3-aryl-benzotriazin-4-one derivatives (13a-e) has been studied, which appears as a modification and/or combination of the benzimidazolone and benzotriazole rings. Only compound 10 shows interesting activity, while the other structural modifications either do not increase (compounds 4 and 5) or reduce (compounds 7 and 13) the pharmacological activity. However, these results provide useful information about structure-activity relationships. PMID- 11765038 TI - Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase C betaI, betaII, zeta in human neutrophils. AB - The protein kinase C (PKC) is a serine/threonine kinase, consisting of different isoforms, implicated in numerous processes of signal transduction. To understand this enzyme well, different pharmacological tools were developed. To activate PKC specifically, phorbol esters were previously used but recent research has shown that these compounds are able to stimulate other proteins. Our model is the respiratory burst in the polymorphonuclear neutrophils. A decrease in the inflammatory process was measured using chelerythrine chloride. Action on PKC was proved by a binding study and by showing the absence of translocation of this enzyme from the cytoplasm to the plasmic membrane during stimulation. PMID- 11765039 TI - Titrimetric micro-determination of therapeutically active phenothiazines using periodate. AB - Two new simple, accurate and precise titrimetric micro-procedures are described for the analysis of phenothiazines in pure sample, tablets, injections and syrup using periodate as the oxidant. The first method is based on the oxidation of phenothiazines with periodate in acid medium and the iodate formed in the reaction is determined by reacting it with iodide and titrating the liberated iodine with thiosulfate after masking the excess of periodate with molybdate. In the second procedure, the unreacted (excess) periodate is determined iodometrically under basic conditions. The reaction conditions have been optimised and the stoichiometry of the reaction has been evaluated. A linear relationship exists between the amount of the drug and the titration end-point as shown by the values of correlation coefficient, r (0.9991-0.9999). The slope of the linear relationship has been calculated and found to be in the range, 0.1457 0.3120. The methods were applied to the analysis of dosage forms with results comparable to those given by the official methods. Both the methods are indirect visual titration methods, and are simpler than, and superior to, many existing methods for the assay of phenothiazines. PMID- 11765040 TI - Statistical evaluation for stability studies under stress storage conditions. AB - During the pharmaceutical development of a new drug, it is necessary to select as soon as possible the formulation with the best stability characteristics. The current International Commission for Harmonisation (ICH) regulations regarding stability testing requirements for a Registration Application provide the stress testing conditions with the aim of assessing the effect of severe conditions on the drug product. In practice, the well-known Arrhenius theory is still used to make a rapid stability prediction, to estimate a drug product shelf life during early stages of its pharmaceutical development. In this work, both the planning of a stress stability study to obtain a correct stability prediction from a temperature extrapolation and the suitable data treatment to discern the reliability of the stability results are discussed. The study was focused on the early formulation step of a very stable drug, Mitonafide (antineoplastic agent), formulated in a parenteral solution and in tablets. It was observed, for the solid system, that the extrapolated results using Arrhenius theory might be statistically good, but far from the real situation if the stability study is not designed in a correct way. The statistical data treatment and the stress stability test proposed in this work are suitable to make a reliable stability prediction of different formulations with the same drug, within its pharmaceutical development. PMID- 11765041 TI - Synthesis and antimicrobial activity of new diazoimidazole derivatives containing an N-acylpyrrolidine ring. AB - A series of 4-diazoimidazole-5-carboxamides bearing in position 2 lipophilic substituents was synthesized and their antimicrobial activity was evaluated in vitro against pathogenic Gram-positive, Gram-negative bacteria and fungi. Some compounds presented antifungal activity, particularly two derivatives (1g and 1h) showed good MIC values (10-50 microg/ml) against both moulds and yeasts. PMID- 11765042 TI - Conformational analysis of carboxyphenylglycine (CPG) derivatives: insight into bioactive and bioselective conformations of group-I mGluRs antagonists. AB - A series of carboxyphenylglycine (CPG) derivatives, endowed with diverse activity and selectivity at metabotropic glutamate receptors (mGluRs), were subjected to an extensive conformational analysis by employing molecular mechanics, semiempirical and ab initio methods. The comparison of the conformational profiles of active and inactive CPGs suggests a possible bioactive conformation characterized by a value of 10 degrees for the N-Calpha-C1Ph-C2Ph angle, with this conformation characterized by ammonium group of the amino acid moiety lying on the plane defined by the aromatic ring. PMID- 11765043 TI - Association of a T262C transition in exon 1 of estrogen-receptor-alpha gene with skeletal responsiveness to estrogen in post-menopausal women. AB - Polymorphic genetic markers of estrogen-receptor-alpha (ERalpha) gene studied so far in osteoporosis reside in non-coding region with uncertain functional significance. The purpose of the present study was to search for nucleotides changes in the exon 1 and 5' regulatory region of ERalpha gene, to study the nature of their linkages to the previously reported Pvull polymorphism in intron 1 and their functional significance in postmenopausal osteoporosis. Direct sequencing of exon 1 and promotor region of ERalpha gene revealed a synonymous nucleotide substitution from T to C at position 262, 29 nucleotides downstream from the putative start codon. No nucleotide change was found in the promotor region. Linkage disequilibrium between the T262C polymorphism and the Pvull polymorphism in intron 1 of ERalpha gene was demonstrated in 129 post-menopausal women (p<0.001). After treating 96 post-menopausal with 0.3 mg or 0.625 mg conjugated equine estrogen (CEE) for 2 yr, vertebral bone mineral density (BMD) increased regardless of the T262C genotype. However, with regard to femoral neck BMD, only those subjects that were homozygous for the T262C polymorphism had an increase in femoral BMD (+5.9+/-1.4%, mean+/-SE; p<0.0001). Using analysis of covariance to assess the effects of the T262C polymorphism, the intronic Pvull polymorphism, doses of CEE and the corresponding baseline BMD on the changes in vertebral or femoral BMD after treatments, it was found that the change in vertebral BMD was related only to the baseline BMD (p<0.05). The change in femoral BMD was independently related to the T262C polymorphism (p<0.01) and the baseline femoral BMD (p<0.01). No effect of the Pvull polymorphism or the doses of CEE on femoral BMD was demonstrated. We concluded that the previously described intronic Pvull polymorphism of ERalpha gene is in linkage disequilibrium with a T262C polymorphism in exon 1. This T262C polymorphism appears to be more directly related to the skeletal response after long-term treatment with estrogen. PMID- 11765044 TI - Thyroid volumes in schoolchildren of Tehran: comparison with European schoolchildren. AB - Since the normative values of thyroid volume ultrasonography results from European schoolchildren were endorsed by the World Health Organization (WHO), few studies have addressed the limitation of the recommended references as universal normative values for thyroid volume. Our objective was to describe thyroid volume measured by ultrasonography in Tehranian schoolchildren and compare them with the WHO normative values. Cross-sectional studies were performed in 2016 schoolchildren, aged 6-15 yr, in Tehran 10 yr after distribution of iodized salt. Data were collected on age, sex, weight, height, thyroid size by palpation and ultrasonography, and urinary iodine. Age/sex and body surface area (BSA) upper limits (97th percentile) of thyroid volume were derived. The goiter prevalence was 42% by palpation, 31% grade 1 and 11% grade 2. Median urinary iodine was 21.2 microg/dl. The 97th percentiles were comparable in girls and boys of all ages. Applying the WHO thyroid volume references to the Tehranian children, they did not show any enlarged thyroid based on BSA and on age, even in 11% of children with grade 2 (visible) goiter. In the Tehranian children, the best predictors of thyroid volume were BSA, height and weight. Using linear regression, the 97th percentile of thyroid volume from Tehranian children were lower than the corresponding references from the WHO normative values. The results indicate that a thyroid volume reference based on weight alone would perform as well as the one based on BSA. In addition, until the adoption of a new applicable international reference for thyroid volume, the use of local reference in the screening of children for thyroid enlargement is recommended. PMID- 11765045 TI - Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects. AB - In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. IN CONCLUSION: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies. PMID- 11765046 TI - Non-palpable thyroid nodules in a borderline iodine-sufficient area: detection by ultrasonography and follow-up. AB - Thyroid ultrasonography was performed in 482 subjects, free of known thyroid disease and living in a borderline iodine-sufficient urban area, to assess the prevalence of non-palpable thyroid nodules and evaluation their evolute during a 3-yr follow-up. The mean (+/-SD) thyroid volume in the whole study group was 10.9+/-3.7 ml and was higher in males (12.9+/-3.6 ml) than in females (9.2+/-2.9 ml) (p<0.0001). Thyroid volume was correlated with body surface, height and weight, while no correlation was present with lean and fat body mass. Goiter was found in 5/256 females and in 13/226 males. Thyroid nodules were found in 27/482 subjects (18 females, 9 males). Single nodules were found in 17/464 subjects (3.66%) with a thyroid gland of normal volume and in 4/18 subjects (22.2%) with goiter (chi2=10.21; p=0.001). Multiple nodules were found in 3/464 subjects (0.6%) with a thyroid of normal volume and in 3/18 (16.6%) subjects with goiter (chi2=24.31; p<0.0001). The prevalence of thyroid nodules was significantly higher in females >35 yr than in those <34 yr (chi2=7.47; p=0.0062). A significant increase (>30%) of nodular volume was found in 5 subjects, while an increased number of nodules was found in 8. In conclusion, thyroid ultrasonography reveals the presence of thyroid nodules in a significant proportion of apparently thyroid disease-free subjects living in a borderline iodine-sufficient urban area. Incidentally discovered thyroid nodules are associated with goiter and are likely to progress in volume and number. PMID- 11765047 TI - Blood levels of atrial natriuretic peptide, endothelin, cortisol and ACTH in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass. AB - Previous studies demonstrated a biphasic time course with post-operative dissociation of blood levels of cortisol and ACTH in patients undergoing major surgery and critically ill patients. A possible role of endothelin and atrial natriuretic peptide (ANP) in the dissociation of concentrations of cortisol and ACTH in critically ill patients has been suggested. In the present study, we investigated the perioperative course of blood levels of endothelin, ANP, ACTH, and cortisol in 13 male patients undergoing cardiac surgery with cardiopulmonary bypass (CPB): group 1 consisted of 7 patients with an uneventful perioperative period and group 2 consisted of 6 patients with perioperative complications. Blood samples were taken pre-[T1], intra-[T2], post-operatively (on the day of surgery) [T3], as well as on the first [T4] and second [T5] post-operative days. Blood samples of endothelin, ANP, cortisol, and ACTH were measured using commercially available immunoassays. Perioperatively, a biphasic time course with post-operative dissociation of ACTH and cortisol concentrations was observed in all patients studied. Intraoperatively, during CPB, the highest levels of endothelin were found. Perioperatively, ANP and endothelin levels were elevated compared to pre-operative values up to the second post-operative day. On the second post-operative day, ANP concentrations were significantly higher in patients with complications in the perioperative period compared to those with an uneventful perioperative period. Our results suggest that: 1) plasma levels of ANP increased in patients with perioperative complications; 2) plasma levels of ANP may have prognostic value for patients undergoing cardiac surgery; and 3) the dissociation of ACTH and cortisol cannot solely be explained by the increase in endothelin-1 and ANP concentrations observed in patients undergoing major surgery. PMID- 11765048 TI - Reduced adrenal response to bacterial lipopolysaccharide in interleukin-6 deficient mice. AB - Administration of bacterial lipopolysaccharide (LPS) in rodents induces the release of pro-inflammatory cytokines [tumor necrosis factor (TNF), interleukin (IL)-1, IL-6] and of ACTH and corticosterone. IL-6 is probably an important cytokine in the interaction between the immune system and the hypothalamus pituitary-adrenal (HPA) axis, but so far the role of IL-6 in lipopolysaccharide (LPS)-induced HPA activation has not been established unequivocally. We examined the effects of intraperitoneal administration of LPS (range 0.25-2000 pg/mouse) on plasma corticosterone, TNFalpha and IL-1alpha levels in IL-6-deficient (IL-6 /-) and wildtype control (IL-6 +/+) mice. Plasma corticosterone levels increased within one hour in both mouse strains. The corticosterone response was significantly reduced in IL-6 -/- mice, but no differences in TNFalpha or in IL 1alpha plasma levels were found between the two strains. Next, we studied the involvement of IL-1alpha or TNFalpha in the responses to LPS in IL-6 -/- and IL-6 +/+ mice by infusion of recombinant human IL-1 receptor antagonist (IL-1ra), or by injection of anti-TNFalpha antibodies. Pretreatment with IL-1ra or with anti TNFalpha did not affect the corticosterone response to LPS, neither in IL-6 -/-, nor in IL-6 +/+ mice. Our data suggest that in the stimulation of the HPA axis by LPS in mice blockade of either IL-1alpha or TNFalpha may be compensated for by other mediators. The reduced adrenal response after LPS administration found in IL-6 -/- mice indicates a distinct role for IL-6 in the activation of the HPA axis by LPS. PMID- 11765049 TI - Loss of heterozygosity of the MEN1 gene in a large series of TSH-secreting pituitary adenomas. AB - Thyrotropin-secreting pituitary adenomas (TSH-omas) are rare tumors (0.5% of all pituitary adenomas) showing an invasive behavior and usually sporadic, although a few cases are associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant inherited syndrome. This disorder is linked to loss of heterozygosity (LOH) on 11q13 and inactivating mutations of MEN1 gene, which is located in the same chromosomal region. As other types of anterior pituitary adenomas, TSH-omas are the result of a monoclonal outgrowth where the intrinsic genetic defects involving oncogenes or tumor suppressor genes occur in a progenitor cell. However, so far no activating mutations of particular oncogenes or inactivating mutations of tumor suppressor genes have been identified. Starting from the observation that 3-30% of sporadic pituitary adenomas show LOH on 11q13, and that allelic losses on the long arms of chromosome 11, beside 10 and 13, are significantly associated with the transition from the non-invasive to the invasive phenotype, we decided to investigate LOH on 11q13 and mutations of menin in a large series of TSH-omas. Thirteen tumors were evaluated. DNA was extracted from tumors by standard methods and genomic DNA from peripheral blood leukocytes was used as control. LOH was screened by using 3 polymorphic markers on 11q13: D11S956, PYGM, INT-2. In 3 out of 15 cases we could demonstrate LOH on 11q13, but none of the tumors showed menin mutation after sequence analysis. These data strongly suggest that menin does not play a causative role in the development of TSH-omas, and are in agreement with other studies demonstrating a limited role of menin in pituitary sporadic tumorigenesis. PMID- 11765050 TI - An exception to the rule: ectopic ACTH production from functional neuroendocrine tissue in an ovarian dermoid cyst. AB - Ectopic ACTH production accounts for 15% of Cushing's syndrome presentations and is characterized by the presence of an excess of ACTH precursors. However in the case presented here ectopic ACTH production was from functional pituitary tissue within an ovarian dermoid cyst. Endocrine investigations showed that the problem behaved more like pituitary-dependent Cushing's disease and this is discussed. Furthermore, this case is one of familial dermoid cysts, another unusual phenomenon. PMID- 11765052 TI - Turner's syndrome mosaicism 45X/47XXX: an interesting natural history. AB - Mosaicism 45X/47XXX is a sporadic form of ovarian dysgenesis. Many of the cases previously described were characterized by a variable phenotype expression. We here report the case of a 33-yr-old woman with recent secondary amenorrhea, weight loss and breast regression. Her menarche had occurred at the age of 11 yr and 6 months and her menstrual cycles had been regular until the age of 28; then, oligomenorrhea and hypertricosis developed. A pelvic ultrasound showed enlarged polycystic-like ovaries and normal uterus. She was treated with ethynil-estradiol and cyproterone acetate for one year. At the age of 31 yr, she underwent a pelvic ultrasound--which revealed normal volume of the ovaries--and hormonal assays including FSH (69 UI/l), LH (113 UI/l), 17beta-estradiol (88 pg/ml), plasma androgens and cortisol levels within normal ranges. No organ-specific autoantibodies toward ovaries, steroid-producing cells or adrenals were found. At the age of 33 yr, there was ultrasound evidence of streak-like ovaries. The patient's height was 145 cm and her weight 45 kg. She had normal female external genitalia, abnormal upper-to-lower body segment ratio, webbed neck, low posterior hair line, cubitus valgus, short and asymmetrical 4th metacarpi, hallux with lateral deviation and moderate scoliosis. No increase in ovarian steroids were found after GnRH-analogue triptorelin (0,1 mg sc) administration. The karyotype analysis on peripheral blood lymphocytes showed a mosaic 45X (90% cells) and 47XXX (10% cells). Diagnostic pelviscopy confirmed streak gonads. Chronic lymphocytic thyroiditis was diagnosed but no cardiovascular or kidney abnormalities were found. A neuro-psychological evaluation revealed emotional and social immaturity, disorders in motorial coordination, visual-spatial organization, as well as reading difficulties and impaired complex phrase construction. The presence of several somatic features of Turner's syndrome, neuro-psychological disorders and an interesting natural history probably depended on the quantitative proportion of 45X to 47XXX cell-lines in different tissues and organs. Estrogen and progestin replacement therapy led to weight gain, re-appearance of secondary sexual characteristics and a mild improvement in mental equilibrium. PMID- 11765051 TI - Multiple endocrine neoplasia type 1Burin from Mauritius: a novel MEN1 mutation. AB - We describe a kindred from Mauritius with an incomplete variant of multiple endocrine neoplasia type 1 (MEN 1Burin). In this family the syndrome is related to a novel MEN 1 gene mutation (deletion of A) at nucleotide 1021 of codon 304 resulting in frame shift and downstream protein truncation at codon 320. Compared to mainstream MEN 1, MEN 1Burin is characterized by a high prevalence of prolactin-secreting pituitary adenomas, late-onset of hyperparathyroidism and rare pancreatic involvement. The family described represents the fifth in the literature with the MEN 1 Burin phenotype; 2 out of the other 4 were related to R460X, Y312X respectively and no mutation within the coding sequence of MEN 1 was found in the other 2. Thus, similar to the classic syndrome, MEN 1Burin phenotype shows poor correlation to MEN 1 genotype. PMID- 11765053 TI - Functioning adrenal black adenoma with pulmonary and cutaneous cryptococcosis: a case report and review of English literature. AB - A 53-year-old woman experienced progressive general weakness and lumbago in the 2 years prior to a physical examination which disclosed cushingoid manifestations and a skin ulcer on the back of her right knee joint. Her plasma cortisol concentration ranged from 24.7 to 31.1 microg/dl, with an ACTH level <5 pg/ml. Urinary excretions of 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17 KS) were 20.5 mg/day and 5.1 mg/day, respectively, and urinary cortisol was also increased (421 microg/day). Cortisol was not suppressed after the administration of 8 mg dexamethasone. Abdominal ultrasound sonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI) studies demonstrated a left adrenal tumor and further, a chest X-ray examination showed a cavitary lesion containing a fungus ball-like mass in the left lower lung field. The serum cryptococcal antigen titer was positive at 1:128 and a bronchoalveolar lavage fluid culture yielded a growth of Cryptococcus neoformans. A biopsy specimen of the skin ulcer also suggested cryptococcosis. As a result, a left adrenectomy was performed, and the excised specimen was shown to be an adenoma consisting of compact cells with abundant pigmentation (black adenoma). A diagnosis of functioning black adenoma of the adrenal gland, complicated with pulmonary and cutaneous cryptococcosis was made. PMID- 11765054 TI - Treatment of multinodular goiter by surgery. PMID- 11765056 TI - Cleavage of the thyrotropin receptor. PMID- 11765055 TI - Exercise-related female reproductive dysfunction. AB - Clinical or biochemical abnormalities of gonadal function, consisting of delayed puberty, luteal phase deficiency, oligo-amenorrhea or anovulation, occur in girls and women participating in strenuous sports. The evidence of a causal relationship between athletic activity and menstrual dysfunction has led to increased interest, also because the number of women who practice sports has increased rapidly. The pathogenesis of exercise-related female reproductive dysfunction (ERFRD) is not completely clarified. The heterogeneity of sports practice, the role of overtraining and other factors, as adequate calorie balance or the assumption of exogenous steroids, could play a primary role in the comprehension of the pathogenic mechanisms of reproductive dysfunction. The interest of physicians about ERFRD is also due to the consequences of reduced gonadal function on women's health. Apart from some short-term transient effects (i.e. on muscle, genito-urinary tract or behavior), hypoestrogenemia can induce long-term deleterious effects, as premature osteoporosis and lifelong impairment of skeletal structure. In view of the possible short-term (infertility) and long term (osteoporosis) consequences of ERFRD, correct physical training and adequate diet approach are mandatory to prevent or to revert neuroendocrine abnormalities so frequently reported in girls and women participating in recreational or competitive athletic activities. PMID- 11765057 TI - "The visceral fat of Bek, Pharaoh's sculptor". PMID- 11765058 TI - Serum DHEAS levels correlate with platelet cGMP in normal women. AB - Several studies suggest that DHEAS is a protective factor against atherosclerosis and coronary artery disease in man, but the mechanism of its biological role is unclear. Recently, it has been suggested that DHEAS can retard atherosclerosis formation through an increase in nitric oxide (NO) production by increasing E2 synthesis. The aim of the study was to evaluate the platelet cGMP concentrations (i.e. a marker of NO production) and the serum levels of DHEAS and E2 in normal females. Blood samples were taken from 51 normal women (age 42.3+/-1.9 yr, range: 22-67 yr, BMI 23.0+/-0.6 kg/m2) to evaluate platelet cGMP concentrations and serum levels of DHEAS and E2. To determine the platelet cGMP content, platelet rich plasma (PRP) was incubated at 37 C (30 min) in the presence of IBMX. The amount of platelet cGMP was measured by a cGMP (3H) assay kit. In all subjects the mean of platelet cGMP was 536.2+/-45.3 fmol/10(6) platelets and the mean of serum DHEAS and E2 was 151.4+/-13.9 microg/dl and 34.7+/-6.1 pg/ml, respectively. In all subjects DHEAS positively correlates with cGMP (p<0.001, r=0.513) and with E2 (p<0.001, r=0.650); furthermore E2 positively correlates with cGMP (p<0.001, r=0.663). In conclusion our data support the hypothesis that DHEAS exerts its antiatherogenic effect by increasing the NO production directly and/or by increasing the E2 synthesis. PMID- 11765059 TI - Technology, biology and traffic. PMID- 11765060 TI - Radiation-induced DNA damage and chromatin structure. AB - DNA lesions induced by ionizing radiation in cells are clustered and not randomly distributed. For low linear energy transfer (LET) radiation this clustering occurs mainly on the small scales of DNA molecules and nucleosomes. For example, experimental evidence suggests that both strands of DNA on the nucleosomal surface can be damaged in single events and that this damage occurs with a 10-bp modulation because of protection by histones. For high LET radiation, clustering also occurs on a larger scale and depends on chromatin organization. A particularly significant clustering occurs when an ionizing particle traverses the 30 nm chromatin fiber with generation of heavily damaged DNA regions with an average size of about 2 kbp. On an even larger scale, high LET radiation can produce several DNA double-strand breaks in closer proximity than expected from randomness. It is suggested that this increases the probability of misrejoining of DNA ends and generation of lethal chromosome aberrations. PMID- 11765061 TI - ATM--a key determinant of multiple cellular responses to irradiation. AB - Ataxia-telangiectasia is a rare clinical disorder manifesting a variety of different abnormalities, including progressive neurodegeneration, increased cancer incidence, immune deficiency, sterility, and extreme radiosensitivity. Recent studies have demonstrated that the defective gene product in this disease, ATM, is a protein kinase. The identification of several different substrates for this kinase is beginning to explain the wide array of different physiologic abnormalities that occur when this gene product is dysfunctional. Since the ATM protein is a critical signaling molecule in the cellular response to ionizing irradiation, the identification of these substrates also results in elucidation of the steps involved in a number of different cellular signaling pathways initiated by irradiation. Such insights also result in the identification of potential new targets for enhancing the efficacy of radiation therapy. PMID- 11765062 TI - Role of retinoblastoma tumor suppressor protein in DNA damage response. AB - Growth arrest induced by DNA damage in mammalian cells requires the function of the retinoblastoma tumor suppressor protein (RB). RB-deficient cells cannot undergo G1, mid-S or G2 arrest following DNA damage, although they can activate the G2 checkpoint, which is reversible. RB-deficient cells are also hypersensitive to DNA damage-induced apoptosis. Induction of apoptosis in RB wild type cells is associated with the loss of RB protein through cleavage by caspase. Two substitution mutations in exon 25 of the Rb gene have been created in the mouse germline to generate the Rb-MI allele that codes for a caspase-resistant RB protein. The RB-MI protein desensitizes cells to apoptosis. Taken together, these results suggest that RB plays a critical role in determining the cell fate following DNA damage. Growth arrest is dependent on RB and apoptosis is activated following RB degradation. PMID- 11765063 TI - p53-mediated apoptosis and genomic instability diseases. AB - Mutations in several DExH-containing DNA helicases, including XPD, XPB, WRN, and BLM, are associated with rare familial cancer syndromes characterized by genomic instability and cancer susceptibility. Known cellular activities of these helicases include DNA replication, repair, recombination, and/or transcription. The p53 tumor suppressor is a regulator of cellular responses to stress, and is biochemically involved in the induction of cell-cycle arrest, apoptosis and DNA repair, all of which contribute to maintenance of genomic integrity. Physical and functional interactions of p53 with DExH-containing DNA helicases have been described. We propose that such interactions could be compromised in inherited disorders and contribute to their cancer susceptibility. In particular, the role of DNA helicases in p53-mediated apoptotic pathways is reviewed. PMID- 11765064 TI - The inherited basis of human radiosensitivity. AB - Certain individuals cannot tolerate 'conventional' doses of radiation therapy. This is known to be true of patients with ataxia-telangiectasia and ligase IV deficiency. Although in vitro testing may not correlate completely with clinical radiosensitivity, fibroblasts and lymphoblasts from patients with both of these disorders have been clearly shown to be radiosensitive. Using a colony survival assay (CSA) to test lymphoblastoid cells after irradiation with 1 Gy, a variety of other genetic disorders have been identified as strong candidates for clinical radiosensitivity, such as Nijmegen breakage syndrome, Mre 11 deficiency, and Fanconi's anemia. These data are presented and considered as a starting-point for the inherited basis of human radiosensitivity. PMID- 11765065 TI - Biological factors influencing optimum fractionation in radiation therapy. AB - Optimum fractionation in radiotherapy occurs when tumor control is improved without enhancement of complications. The main influence on choice of overall time, total dose and fraction size is biological: the proliferation status of tumors. For rapidly proliferating tumors, shorter schedules than 6 to 8 weeks are necessary. Optimum overall time is similar to Tk, the time after beginning cytotoxic treatment when rapid proliferation in tumors starts: 21 to 35 days in head and neck tumors. These, and non-small cell lung tumors, have a clonogenic cell doubling time during radiotherapy of about 3 days. New developments in designing optimum schedules for such tumors are presented: carefully regulated hypofractionation (CRH). For slowly proliferating tumors, especially prostate adenocarcinoma, intracellular repair is large, so larger doses per fraction will be necessary. New evidence is presented showing that their alpha/beta ratio may indeed be lower than 3 Gy. For an entirely different reason from that above, hypofractionation should be tested. PMID- 11765066 TI - Generalization of the normalized dose-response gradient to non-uniform dose delivery. AB - A generalization of the standard dose-response gradient to arbitrarily heterogeneous dose distributions has been developed. The generalized dose response gradient is the scalar product of the vector representing the dose distribution and the gradient of the dose-response relation with respect to that dose vector. It is shown that, for a tumor, the individual gamma-values for each portion of the tumor divided by the corresponding local tumor control probability should be added to get the total value for the heterogeneously irradiated tumor. This corresponds to summing up the contributions of all tumor volumes so that the total value of the gradient is related to the logarithm of the total tumor clonogen number. General expressions are also derived for the change in the dose response relation as a function of a change in the delivered dose distribution. PMID- 11765067 TI - Biologically optimized radiation therapy. AB - Advanced treatment optimization is possible using quantitative radiobiological dose response models. Although all present models are necessarily linked to a certain degree of uncertainty, this will only have a small influence on the relative shape of the resultant optimal dose distribution. However the exact dose level should perferably be determined clinically by dose escalation with the optimized dose plan as a control arm. It is shown that a large part of the biological effect of high linear energy transfer radiation is due to the spectrum of low-energy delta-electrons that can generate dense clusters of complex DNA damage. Such electrons are efficiently generated by low-energy photons or densely ionizing ion beams and to a considerably smaller degree by high-energy electrons, photons and protons. A new analytical expression is developed for the effective radiation resistance of heterogeneous tumors, making it possible to approximate the response of such tumors by the effective clonogen number N0,eff and the effective D0 value D0,eff. It is shown that a relatively small number of resistant tumor cells may well be sufficient to dominate the response of hypoxic or otherwise heterogeneous tumors. Finally, several examples are given of intensity-modulated dose distributions generated by multiple radiation modalities, the total effect of which is biologically optimized. PMID- 11765068 TI - Molecular targeting of gene therapy and radiotherapy. AB - The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFalpha. The therapeutic gene (TNFalpha) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments. PMID- 11765069 TI - P53 gene replacement for cancer--interactions with DNA damaging agents. AB - Clinical trials of p53 gene replacement have provided information that will be useful in the design of future gene therapy strategies. Direct intratumor injection has low toxicity and thus can be readily combined with existing treatments. Post-injection gene expression can be documented and occurs in the presence of an anti-adenovirus immune response. Importantly, this treatment can cause tumor regression or prolonged stabilization. Future research directions will include development of more efficient vectors, use of novel genes, and combined modality approaches. Unresectable tumors are a prominent problem in oncology, with proven therapies such as radiotherapy and chemotherapy controlling less than 20% of lung cancers. Based on the preclinical and clinical studies discussed, it now seems that these conventional therapies may provide renewed potential when used in conjunction with transfer of a functional p53 gene. PMID- 11765070 TI - Randomized trial of opioids versus tricyclic antidepressants for radiation induced mucositis pain in head and neck cancer. AB - Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p = 0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment. PMID- 11765071 TI - Effects of Na-sucrose octasulfate on skin and mucosa reactions during radiotherapy of head and neck cancers--a randomized prospective study. AB - Na sucrose octasulfate (Na SOS) was tested for ability to relieve radiation induced acute skin and mucosal reactions in patients with head and neck cancer. Sixty patients were included in this prospective, double-blind, randomized study. Skin and mucosal reactions were scored using several variables. No statistically significant difference was found between the results with Na SOS and those with placebo for any of the variables, with the exception of skin desquamation, which showed a significant difference in the placebo group. The most likely explanation for this is that the Na SOS gel itself left behind a flaky layer that was difficult to distinguish from radiation-induced flaking. In conclusion, we cannot recommend Na SOS in the routine management of radiation-induced skin and mucosal reactions. PMID- 11765072 TI - Acute side effects after dose-escalation treatment of prostate cancer using the new urethral catheter BeamCath technique. AB - Acute side effects after dose-escalated radiotherapy for prostate cancer with different treatment techniques were evaluated, using a daily diary recorded by the patients. Dose escalation was performed using the urethral catheter BeamCath' technique. Side effects were evaluated in 267 patients by means of a daily diary during the treatment and at 3-months' follow-up. The patients' evaluations were compared with those of patients treated with conventional or conformal techniques. Looser stools were reported in the conventional (placebo) and 76 Gy groups at 3-months' follow-up compared with at week 1. No other obvious increase in rectal or bladder morbidity was seen in the 76 Gy group. The catheter did not increase the urinary frequency in comparison to the other groups. The reported urgency and starting problems at the beginning of treatment seemed to improve in all groups at 3-months' follow-up. External beam radiotherapy dose escalation using the BeamCath technique did not result in a dose-dependent increase in acute side effects. PMID- 11765073 TI - Impact of cancer on primary caregivers of patients receiving radiation therapy. AB - The main objective of this study was to assess the consequences of caregiving on primary caregivers of Greek cancer patients receiving radiotherapy. Sixty-five caregivers participated in the study and data were collected through structured interviews. Our results pointed to a lack of association concerning extent of patients' disease, treatment schedule, performance status or awareness of diagnosis. However, female caregivers with low qualifications, partners, and those living with the patient were more likely to report heightened symptoms of anxiety and depression, severe impact of caregiving on their lives, poor health and low quality of life. In addition, it was shown through multivariate analyses that psychological distress was the sole predictor of overall health and global quality of life. In conclusion, Greek caregivers are to a great extent affected by the disease. Caring for significant others is essential to promoting quality of life for the family and the patient. PMID- 11765074 TI - The nation-wide Swedish family-cancer database--updated structure and familial rates. AB - The Swedish Family-Cancer Database was expanded to include all Swedes born in 1932 and later (offspring) with their parents, totaling 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from the years 1958 to 1998, including over 1 million primary cancers and in situ tumors. Some 10%, of offspring diagnosed with cancer lack any parental information. Incidence rates of cancers were similar in the database and in the Cancer Registry to age 70, but at higher ages the rates in the Database were lower, probably because of selection. The familial risk for all types of cancer in offspring was 1.73 when a parent had the same type of cancer. The familial rates were increased for all main cancer sites, except for the upper aerodigestive tract, stomach, liver, pancreas and bone marrow (leukemia). The rates were 7.47 for thyroid, 4.69 for testis, and over 2.00 for melanoma, ovary, prostate, skin, endocrine glands and endometrium. PMID- 11765075 TI - Graphical method for the calculation of chromatographic performance in representing the trade-off between purity and recovery. AB - A simple engineering framework that enables the rapid representation of the performance of liquid chromatographic separations is provided in this paper. The fractionation diagram and its associated maximum purification factor versus product yield, and contamination index versus product yield diagrams, may be derived directly from chromatographic data. The fractionation diagram plots the relative change in the cumulative fractional mass of product eluted with the corresponding fractional total mass eluted, while the maximum purification factor versus yield diagram shows the degree of trade-off between the levels of purity and recovery achieved in the chromatographic step. The minimum contamination index versus yield plot is especially suitable for cases where the product and impurity are expressed in different units and shows how the extent of contaminant removal changes relative to product yield. These diagrams are more straightforward and easily interpretable compared to the basic conventional chromatograms and enable investigation of the degree of trade-off between purity and recovery for any set of operating conditions to be made. The approach is demonstrated for two different chromatographic systems. In the first, a set of simulation results from a verified size exclusion model is used to demonstrate the approach for product recovery. In the second, a set of experimental results for the removal of endotoxin from DNA is used. This demonstrates a problem where the product and impurity content are measured by different assay techniques and are expressed in different units, and also where the quality of process information is limited by the small number of fractions collected. The studies show how such an approach can help to identify the optimal operating conditions, in terms of acceptable yield and desired level of contaminant removal, and to redefine the location of product fractions needed to achieve these specifications. PMID- 11765076 TI - Mechanisms effecting analysis of volatile flavour components by solid-phase microextraction and gas chromatography. AB - Quantitative properties of solid-phase microextraction (SPME) have been studied in order to investigate a simple and reliable method for analysing volatile flavour components in strawberries. Monitoring the chemical composition profile of berries will be of interest for the producers in order to optimise growth and storage conditions. By the use of SPME and capillary gas chromatography selected standard components were quantified with accuracy within +/-7% and a linear response were found in all concentration ranges studied, covering three orders of magnitude. Equilibrium constants that describe how various components are distributed between the three phases present, sample, headspace and fibre coating were determined. In the system studied, the majority of analytes remained in the sample. This means that repeated analysis can be performed from a single sample without significantly changing the results. The mass transfers of the flavour components, from the sample and into the fibre, were fitted to a transport model assuming that the rate-controlling step is diffusion within the fibre. The experimental results agreed well with the model for most of the components studied. The response for three of the components (geraniol, linalool and trans-2 hexenyl butanoate) did not agree with the model. These components were present in the gas phase in only minute amounts explaining the deviation from the model. Such components will require a long absorption time (longer than 30 min). For quantitative analysis, it is important to use a very precise pre-determined absorption period and well defined sampling conditions. Internal standards can be omitted. PMID- 11765077 TI - Flow-through sampling for electrophoresis-based microfluidic chips using hydrodynamic pumping. AB - This work presents a novel electrophoretic microchip design which is capable of directly coupling with flow-through analyzers for uninterrupted sampling. In this device, a 3 mm wide sampling channel (SC) was etched on quartz substrate to create the sample inlet and outlet and the 75 microm wide electrophoretic channels were also fabricated on the same substrate. Pressure was used to drive the sample flow through the external tube into the SC and the flow was then split into outlet and electrophoretic channels. A gating voltage was applied to the electrophoretic channel to control the sample loading for subsequent separations and inhibit the sample leakage. The minimum gating voltage required to inhibit the sample leakage depended on the solution buffer and increased with the hydrodynamic flow-rate. A fluorescent dye mixture containing Rhodamine B and Cy3 was introduced into the sample stream at either a continuous or discrete mode via an on-line injection valve and then separated and detected on the microchip using laser-induced fluorescence. For both modes, the relative standard deviation of migration time and peak intensity for consecutive injections was determined to be below 0.6 and 8%, respectively. Because the SC was kept floating, the external sampling equipment requires no electric connection. Therefore, such an electrophoresis-based microchip can be directly coupled with any pressure-driven flow analyzers without hardware modifications. To our best knowledge, this is something currently impossible for reported electrophoretic microchip designs. PMID- 11765078 TI - Capillary zone electrophoresis with electrochemical detection--a simple and effective method to analyze oxygen-consuming and peroxide-forming processes. AB - Numerous biological, chemical and photochemical processes consume molecular oxygen, thereby forming peroxides, hydroperoxides and even hydrogen peroxide. This paper describes a new system for monitoring quasi simultaneously oxygen uptake and peroxide formation. For this purpose capillary electrophoresis with electrochemical detection was connected to a new automated injector that periodically injects a sample of the reaction mixture into the capillary electrophoresis system without any contact with the atmosphere. The device was tested with some pharmacologically relevant reactions such as enzymatic oxidation of glucose catalyzed by glucose oxidase, enzymatic lipid oxidation by lipoxygenase and the photodynamic reaction of the anti-inflammatory drug ketoprofen. PMID- 11765079 TI - Effects of bovine serum albumin heterogeneity on frontal analysis with anion exchange media. AB - The presence of dimers in commercial bovine serum albumin (BSA) samples of nominal high purity is investigated along with their effects on the frontal analysis behavior of preparative anion-exchange media. Size-exclusion and analytical anion-exchange chromatography are used to determine the relative amounts of monomer and dimer for two samples of BSA. While the amount of dimer was generally low, its impact on adsorptive behavior is significant. Equilibrium experiments demonstrate that the anion-exchange media binds the dimer more strongly, leading to an unequal distribution of the monomer and dimer between the two phases. Analysis of the breakthrough behavior of BSA reveals that the monomer breaks through prior to the dimer. This leads to the characteristic tailing breakthrough curve often seen with BSA. Breakthrough experiments carried out using dimer-free BSA confirm that the extreme tailing observed with the commercial samples is curtailed by removing the dimer. PMID- 11765080 TI - Separation of enantiomers of ibuprofen on chiral stationary phases by packed column supercritical fluid chromatography. AB - A packed column supercritical fluid chromatography (SFC) method for the separation of ibuprofen enantiomers on a chiral stationary phase and CO2 with modifier as mobile phase has been developed at an analytical scale. Among 11 different stationary phases the Kromasil CHI-TBB phase showed by far the best separation properties. The influence of different modifiers, injection solvents, temperature, and pressure, and density of the fluid, respectively, on the separation behavior has been studied. It was found that the separation behavior strongly depends on the type of modifier and the modifier content. Temperature and pressure are of less influence. PMID- 11765081 TI - Use of porous graphitic carbon coupled with mass detection for the analysis of polar phenolic compounds by liquid chromatography. AB - Phenolic compounds present in olive mill wastewater (OMW) need to be quantified because of their pollution capacity toward the environment. In the present study, six representative phenolic compounds of OMW were chosen to develop a LC-MS method. The high polarity of the compounds caused problems when using traditional reversed-phase liquid chromatography (RPLC). Consequently, a method was developed on another kind of chromatographic phase: Porous Graphitic Carbon (PGC) involving the use of a tetrahydrofuran (THF) gradient. The influence of THF as mobile phase in LC-MS coupling, which is not common practice, was evaluated. In Atmosperic Pressure Chemical Ionisation (APCI) in the negative ion mode, the presence of THF in the mobile phase did not degrade the MS signal of the target compounds in the conditions studied. On the contrary, an improvement was even observed when the percentage of THF increased. The proposed PGC-LC-MS method was selective and linear for the six phenolic compounds analysed with limits of quantification lower than 5 ppm in all cases. The precision was satisfactory (pooled RSD around 6%). The analyses of OMW matrix spiked sample confirmed the good performance of the proposed method. PMID- 11765082 TI - New reversed-phase liquid chromatographic method to detect aflatoxins in food and feed with cyclodextrins as fluorescence enhancers added to the eluent. AB - The effect of succynil-beta-cyclodextrin (beta-CD-Su), dimethyl-beta-cyclodextrin (DIMEB) and beta-cyclodextrin (beta-CD) on the fluorescence of aflatoxins B1, B2, G1, G2 and M1 (AFB1, AFB2, AFG1, AFG2 and AFM1) was studied: beta-CD-Su promoted the largest fluorescence enhancement for AFB1 and AFM1 while DIMEB showed better results for AFG1 . On the basis of the fluorescence enhancement, a new RP-HPLC method for detecting aflatoxins B1, B2, G1, G2 and M1 was developed using cyclodextrins directly dissolved in the LC eluent. Aflatoxins B1, B2, G1 and G2 were resolved using a MICRA NPS ODS-1 column using methanol-water as mobile phase to which 6 x 10(-3) M beta-CD-Su or beta-CD were added. Chromatographic responses of AFB1 and AFG1 achieved using beta-CD dissolved in the mobile phase were enhanced, respectively, 8 and 12 times, and 10 and 15 times with beta-CD-Su. Detection limits lower than 0.3 microg/kg were achieved for all the four aflatoxins. Aflatoxin M1 was analysed using a Spherisorb S3 ODS-2 Narrow Bore column and methanol-water as mobile phase with added 2 x 10(-3) M beta-CD-Su. An area enhancement of 1.5 was detected for the toxin and the detection limit achieved under these analytical conditions was lower than 0.0005 microg/kg. Both methods were statistically validated showing a linear response for all the aflatoxins tested (R2 > or = 0.99), and applied to the analysis of spiked and naturally contaminated food samples. PMID- 11765083 TI - Studies of signal suppression in liquid chromatography-electrospray ionization mass spectrometry using volatile ion-pairing reagents. AB - Volatile ion-pairing reagents are useful due to their compatibility with liquid chromatography-electrospray ionization (ESI) mass spectrometry. In this study trifluoroacetic acid, heptafluorobutanoic acid and perfluoroheptanoic acid were used as ion-pairing reagents. The signal intensities of eight amine analytes were measured in the presence of these fluorinated carboxylic acids and compared with the signal intensity when using an ion-pair free formic acid-ammonium formate buffer. It was shown that the ESI signal from most of the studied analytes decreased about 30-80% when the fluorinated carboxylic acids were added to the mobile phase at useful concentrations. The use of these acids in ion-pair chromatography was also compared to the more conventional sodium heptane sulphonate additive. It was found that the chromatographic performance was comparable. Finally, the long-term performance of the ESI interface and the chemical background caused by these fluorinated reagents were examined. No degradation of the ESI interface performance could be seen for over 24 h of continuous infusion. PMID- 11765084 TI - Matrix solid-phase dispersion extraction and high-performance liquid chromatographic determination of residual sulfonamides in chicken. AB - Simultaneous determination of the six sulfonamides (SAs) sulfadiazine, sulfadimidine, sulfamonomethoxine, sulfamethoxazole, sulfadimethoxine and sulfaquinoxaline in chicken using matrix solid-phase dispersion (MSPD) with neutral aluminium oxide as an MSPD sorbent and high-performance liquid chromatography (HPLC) is presented. In the present MSPD, six SAs could be isolated by only one step, elution with a 70% (v/v) aqueous ethanol solution, without the sorbent conditioning and the sorbent-tissue matrix washing. For the HPLC determination, a LiChrospher 100 RP-8 and a mixture of 1% acetic acid solution (pH 3.0, in water)-acetonitrile-N,N-dimethylformamide (78:22:5, v/v/v) as the mobile phase with a photodiode array detector were used. Average recoveries were greater than 87.6% with relative standard deviations between 0.5 and 8.6%. The total time and amount of solvent required for the analysis of one sample were <1.5 h and <12 ml, respectively. PMID- 11765086 TI - On the signal response of various pesticides in electrospray and atmospheric pressure chemical ionization depending on the flow-rate of eluent applied in liquid chromatography-tandem mass spectrometry. AB - The API-MS signal response of several pesticides (atrazine, simazine, isoproturon, diuron, chlorfenvinphos, chlorpyrifos, alachlor, trifluralin) depending on the flow-rate of eluent entering the MS interface was investigated. The investigations were based on API-MS-MS analyses of standard pesticide mixtures in the flow injection mode (FIA) at systematically varied eluent flow rates using both an ESI interface (Turboionspray) and a heated nebulizer type APCI source. In the result, the individual compounds included in this study showed significant differences in their signal response behaviour depending on the flow-rate of eluent applied. The most hydrophobic compounds among the investigated pesticides (chlorpyrifos and trifluralin) showed drastic losses of sensitivity with increasing eluent flow-rate in both ESI and APCI, while more hydrophilic compounds like atrazine, simazine and isoproturon showed the expected signal response (concentration-sensitive in ESI, mass-flow-sensitive in APCI) at least within a certain range of flow-rates (200-600 microl/min in ESI, 200-2000 microl/min in APCI). These findings lead to the conclusion that application of a programmed HPLC eluent flow-rate may be advantageous to achieve maximum sensitivity of API-MS detection for all pesticides of interest. This is exemplified by the implementation of a flow gradient into an online SPE-HPLC-APCI MS/MS method for improved analysis of pesticides in drinking water. PMID- 11765085 TI - Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography. AB - A novel ion chromatographic method was proposed for the simultaneous determination of artificial sweeteners (sodium saccharin, aspartame, acesulfame K), preservatives (benzoic acid, sorbic acid), caffeine, theobromine and theophylline. The separation was performed on an anion-exchange analytical column operated at 40 degrees C within 45 min by an isocratic elution with 5 mM aqueous NaH2PO4 (pH 8.20) solution containing 4% (v/v) acetonitrile as eluent, and the determination by wavelength-switching ultraviolet absorbance detection. The detection limits (signal-to-noise ratio 3:1) for all analytes were below the sub microg/ml level. Under the experimental conditions, several organic acids, including citric acid, malic acid, tartaric acid and ascorbic acid, did not interfere with the determination. The method has been successfully applied to the analysis of various food and pharmaceutical preparations, and the average recoveries for real samples ranged from 85 to 104%. The levels of all analytes determined by this method were in good agreement with those obtained by the high performance liquid chromatographic procedure. The results also indicated that ion chromatography would be possibly a beneficial alternative to conventional high performance liquid chromatography for the separation and determination of these compounds. PMID- 11765087 TI - Performance of programmed temperature vaporizer, pulsed splitless and on-column injection techniques in analysis of pesticide residues in plant matrices. AB - A programmed temperature vaporizer (PTV) injection technique has been recently implemented in our laboratory. In present paper its performance is compared with other GC injection techniques commonly used in trace analysis of organic contaminants. Twenty-six pesticides representing different chemical classes were selected for the study. This group comprised compounds typically subjected to discrimination in the injection port of the gas chromatograph, e.g., polar organophosphorus pesticides and thermolabile carbamates. In the first set of experiments standards in pure solvent were injected into GC systems employing different types of injection, i.e., (i) on-column, (ii) pulsed splitless, (iii) PTV solvent split, (iv) PTV splitless, and the responses of analytes were compared. Discrimination of troublesome compounds was significantly decreased with the application of PTV solvent split injection. In the second set of experiments repetitive injections of purified wheat samples were performed, with aims to evaluate the long-term stability of responses, as well as matrix effects in different stages of system contamination for each injection technique. The tolerance of the GC system to co-injected matrix components was increased in the order: on-column20, 24>5beta>17alpha>>14alpha. PMID- 11765090 TI - Suicide prevention: increasing education and awareness. AB - Suicide is a serious and complex public health problem. Health care providers, including both psychiatrists and primary care physicians, are just beginning to understand the intricacies involved in suicide and its prevention. Suicide rates continue to rise, making the education of the public and physicians regarding awareness and prevention, recognition of a wide range of risk factors, and research into suicide prevention strategies very important. PMID- 11765091 TI - Intervention research with persons at high risk for suicidality: safety and ethical considerations. AB - There is a critical need for studies designed to reduce suicidality. Individuals at high risk for suicidality deserve safe and effective treatments, just as do other individuals with mental disorders who do not experience suicidality. Points for consideration regarding safety and monitoring procedures are offered to help researchers who conduct treatment trials with individuals who have mental disorders and investigators specifically interested in developing treatments to reduce suicidality. Issues such as study design, increased monitoring and supervision, research clinician competencies, and liability concerns are addressed. Points to consider in planning an intervention trial, a checklist of informed consent issues, and a list of relevant active federal regulations are provided. PMID- 11765092 TI - Mood disorders and suicide. AB - The mood disorders unipolar major depression and bipolar disorder increase the risk of suicidal ideation, attempted suicide, and death by completed suicide. This article reviews the epidemiologic data on the relationship between mood disorders and suicide, with an emphasis on the substantial risk of suicide, while reassessing older data that may no longer apply. Widespread underdiagnosis and undertreatment of major depression and bipolar disorder contribute to an unacceptable risk of suicide, a preventable tragedy. PMID- 11765093 TI - Integration of suicide prevention into outpatient management of bipolar disorder. AB - Suicide prevention is a critical objective in the treatment of bipolar disorder. This article describes practical mechanisms by which monitoring and management of suicide risk can be integrated into the routine care of patients with bipolar disorder. Suicide risk is assessed in terms of inclination (the drive to commit a self-destructive act) and opportunity (access to lethal means). Intervention strategies are adapted to the needs of bipolar patients across 3 phases of treatment: the acute episode; the continuation phase, when symptom reduction has occurred but adaptive recovery has not; and the maintenance phase, in which optimization of adaptive function and vigilance against impending relapse are paramount. Integration of suicide prevention into the outpatient management plan begins with a routine discussion of suicide risk at the initiation of a treatment relationship, even in the absence of other known risk factors. This discussion paves the way for ongoing assessment of suicidality. Just as the recommended routine monitoring of every euthymic bipolar patient includes at least some minimal assessment for prodromal symptoms of acute mania or depression, every clinical visit can include sufficient probes to determine the need for new interventions specific to suicide prevention. Ongoing assessment of risk and protective factors can be linked to a range of individualized interventions designed to meet the varying needs of patients over time. The intensity of monitoring and interventions reflects the clinician's knowledge of risk factors and may be life saving, but it is also important that patients and others involved in their care understand that monitoring cannot guarantee safety. PMID- 11765094 TI - Identifying and managing suicide risk in bipolar patients. AB - Bipolar patients have been shown to be at high risk for suicidal behavior. Therefore, identifying potentially suicidal patients is necessary in the treatment of bipolar patients. A stress-diathesis model for suicidal behavior has been proposed to assist clinicians in determining which patients are at risk. In the model, suicidal behavior is the result of the interaction between an individual's threshold for suicidal acts and the stressors that can lead to suicidal behavior. Suicide risk factors can then be categorized as either diathesis-related or stress-related. In a study applying the model of suicidal behavior to bipolar disorder, bipolar patients who attempted suicide had higher levels of suicidal ideation, lifetime aggression, and substance abuse than the comparison group of nonattempters. Attempters had twice the number of major depressive episodes. Once high-risk patients are identified, their suicide risk can be managed through treatments such as prophylactic lithium treatment and other pharmacologic approaches. PMID- 11765095 TI - Suicidality and substance abuse in affective disorders. AB - The relationship between suicidality and substance abuse has long been recognized, although studies have only fairly recently begun to identify factors that may help clarify how alcohol or other drug abuse increases the susceptibility to suicidal behavior in vulnerable populations. In particular, alcohol and other psychoactive substance misuse has been linked with mood destabilization and the induction of manic or depressive episodes in affectively ill individuals, while also demarcating groups with heightened tendencies toward impulsivity, aggression, and sensitivity to interpersonal loss. Serotonergic mechanisms have been implicated in each of these clinical settings, along with possible dysregulation of other neurotransmitter systems. Psychosocial aspects of alcohol or drug abuse relevant to suicide may involve a heightened sensitivity to interpersonal loss, poor coping skills in response to adverse life events, and affective dysregulation induced by circadian and psychosocial stresses. Consequently, self-destructive behaviors with relatively little premeditation may arise during periods of increased stress, intoxication, depression, or other psychopathology. Early detection of substance abuse followed by appropriate pharmacologic and/or psychotherapeutic interventions may greatly help to minimize the formation of complex comorbid psychiatric conditions and reduce the potential for suicidal acts among high-risk populations. PMID- 11765096 TI - A family member's legal experience with an insurer's refusal to recertify inpatient mental health treatment. AB - My son Nathaniel has bipolar disorder and was hospitalized for 6 months, during which time our insurance company was prepared to refuse certification more than once despite a policy that included 365 days of inpatient mental health treatment. A break in coverage by the insurance company would have meant that Nathaniel, still suicidal, would not receive the life-saving care he needed. Fortunately, I am a lawyer, which enabled me to act as a legal advocate for my son when our insurer threatened not to recertify. Because my son's experience with the insurance company is not unusual--many patients with mental illness struggle with insurance companies who refuse to certify treatment--I believe that the family or support people of seriously ill psychiatric patients should be prepared to act in circumstances similar to mine. Psychiatric inpatient units should, as a matter of course, provide information on legal remedies that can be obtained before irreparable harm occurs. PMID- 11765097 TI - Pharmacologic interventions in suicide prevention. AB - Suicide rates vary by country and by mental disorder. What does not vary, though, is that the number of suicides per year is not declining and that a person with a mental disorder is more likely to commit suicide than one without such an illness. Although many pharmacologic interventions have been reported to reduce the risk of suicide among mentally ill patients, especially those with bipolar disorder, the effects of such interventions are inconsistent at best. Lithium is the only medication for which the evidence consistently shows an antisuicidal effect. PMID- 11765098 TI - Psychosocial approaches to suicide prevention: applications to patients with bipolar disorder. AB - Hopelessness, dysfunctional attitudes, and poor problem-solving abilities are psychosocial risk factors that have been identified as predictors of suicide. These psychosocial risk factors may help clinicians apply specific therapies and treatments to patients with bipolar disorder at risk for suicide. A search of the literature on suicide prevention revealed 17 randomized, controlled studies, which the authors reviewed to determine the efficacy of strategies aimed at eliminating psychosocial risk factors for suicide. Three strategies emerged as efficacious: (1) applying interventions to elicit emergency care by patients at times of distress; (2) training in problem-solving strategies; and (3) combining comprehensive interventions that include problem solving with intensive rehearsal of cognitive, social, emotional-labeling, and distress-tolerance skills. On the basis of their review of the literature, the authors make recommendations for suicide prevention for patients with bipolar disorder. PMID- 11765099 TI - Nonnarcotic analgesics: appropriate to include in a study of illicit drug use? PMID- 11765100 TI - Did viewpoint mischaracterize Danish TOM methods? PMID- 11765101 TI - Protocol Underemphasizes beta-blockers. PMID- 11765102 TI - Liver disease also affects pharmacokinetics of statins. PMID- 11765103 TI - Personal digital assistants are advancing pharmacy practice. PMID- 11765104 TI - Major career decisions: pursuing postgraduate training. PMID- 11765105 TI - September 11. PMID- 11765106 TI - Perspectives on generic pharmaceuticals: some conclusions. PMID- 11765107 TI - The pharmaceutical sciences in America, 1902-1952. PMID- 11765108 TI - Fighting back: pharmacists' roles in the federal response to the September 11 attacks. PMID- 11765109 TI - Immunizations for high-risk populations. PMID- 11765110 TI - Pharmaceutical care in chain pharmacies: beliefs and attitudes of pharmacists and patients. AB - OBJECTIVE: To discuss with pharmacists and patients with reactive airways disease their beliefs about pharmaceutical care and the pharmacist's role in health care, obstacles to providing pharmaceutical care in community pharmacies, and strategies to overcome these obstacles. DESIGN: Two focus groups of patients, two focus groups of pharmacists. PARTICIPANTS: Thirteen patients with reactive airways disease and 11 chain pharmacists. MAIN OUTCOME MEASURES: Qualitative reports on the pharmacist's role in health care delivery and obstacles to implementing pharmaceutical care programs. RESULTS: Pharmacists wished to provide pharmaceutical care, and patients were supportive of pharmacists' involvement in their health care. Both viewed counseling as an important role for pharmacists and believed that pharmacists should work with patients' physicians. Reported obstacles included lack of time, inadequate privacy, and pharmacists' lack of direct access to patients' physicians. Pharmacists and patients believed pharmacists should have access to patient-specific clinical data. CONCLUSION: Focus groups provided valuable information for designing pragmatic pharmaceutical care. The obstacles and possible solutions identified through the discussions represent fertile ground for designing innovative pharmaceutical care programs. PMID- 11765111 TI - Understanding the scientific issues embedded in the generic drug approval process. AB - OBJECTIVE: To review the major scientific issues embedded in the generic drug approval process. DATA SOURCES: Articles indexed initially under terms such as generic medications, generic drugs, bioequivalence, and bioinequivalence. These terms were used to search indexing services such as MEDLINE, International Pharmaceutical Abstracts, CINAHL (a database of nursing and allied health literature), and Science Citation Index. Additional data sources included the Code of Federal Regulations and regulatory guidances from the Food and Drug Administration (FDA) Center for Drug Evaluation and Research. STUDY SELECTION: Performed by the authors. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Despite the fact that regulations regarding bioequivalence have been in place for more than 20 years, controversies over bioequivalence continue to arise. Consensus on many of these issues is driving the development of new FDA guidances regarding bioequivalence. Still, despite the issuance of new guidance and consensus building among scientists, many clinicians and consumers remain uninformed regarding the scientific basis for establishing bioequivalence and the generic drug approval process in general. Although some have suggested that the generic drug approval process is flawed, overall, it appears that the process works. CONCLUSION: Understanding the generic drug approval process and the issues surrounding bioequivalence is of paramount importance to both clinicians and scientists. PMID- 11765112 TI - Drug product selection: legal issues. AB - OBJECTIVE: To review the potential legal liability of the pharmacist in the drug product selection process. DATA SOURCES: Published articles identified through MEDLINE, published law reviews identified through InfoTrac, and appellate court decisions. Search terms used included pharmacist liability, drug product selection, and generic substitution. Additional articles, books, and appellate court decisions were identified from the bibliographies of retrieved articles and citations in appellate court decisions. DATA SYNTHESIS: Pharmacists engaging in drug product selection are civilly liable under three legal theories: negligence, express or implied warranties, and strict product liability. Potential criminal liability includes prosecution for insurance fraud, deceptive business practices, and violation of state drug product selection laws and regulation. CONCLUSION: Pharmacists increase their liability when engaging in drug product selection, but the increase is small. Still, the law continues to evolve as pharmacists seek expanded roles and responsibilities. When courts give closer examination to pharmacists' expanded role, it is likely that pharmacists' liability will increase. PMID- 11765113 TI - Oral contraceptives: an update on health benefits and risks. AB - OBJECTIVE: To review the health benefits and risks of oral contraceptives, with an emphasis on emerging noncontraceptive benefits and the pharmacist's role in promoting safe and effective use of these widely prescribed medications. DATA SOURCES: Published articles identified through MEDLINE (1995-2001) using the search terms oral contraception, neoplasms, cardiovascular disease, menstrual cycle, and other pertinent subject headings. Additional articles and books were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: Combined oral contraceptives (COCs), which contain synthetic estrogen and progestin, are the second most common form of birth control for women after sterilization. When taken properly, COCs are highly effective, with a pregnancy rate of 0.1% among perfect users. Also, a growing body of evidence points to multiple noncontraceptive benefits of COCs, including protection from several types of cancer and a variety of gynecologic benefits, such as reduced menstrual bleeding irregularities and fewer ectopic pregnancies. COCs are one of the most studied classes of medications, and they have been found to have an excellent safety profile in nonsmoking healthy women. They may be used continuously until menopause. For women with coexisting medical conditions or other special circumstances, the risks and benefits of COCs must be carefully evaluated before use. CONCLUSION: More than 40 years after their introduction, COCs remain the leading form of hormonal contraception. By assessing patients' contraceptive needs, evaluating their risk factors, and providing sensitive and thorough counseling, pharmacists can help ensure the safe and effective use of these medications. PMID- 11765114 TI - Pharmacist counseling of pregnant or lactating women. PMID- 11765115 TI - Allergic rhinitis: nothing to sniffle at. PMID- 11765116 TI - Antiangiogenesis agents in clinical trials. PMID- 11765117 TI - How do herbal resources measure up? PMID- 11765118 TI - Biological and chemical terrorism: recognition and management. AB - Primary care physicians will be on the front line in detecting and managing any future terrorist attacks that use chemical or biological agents. This article reviews how to recognize and treat disease caused by exposure to nerve agents, blistering agents, hydrogen cyanide, ricin, anthrax, smallpox, plague, and botulinum toxin. PMID- 11765119 TI - GP IIb/IIIa inhibitors in coronary artery disease management: what the latest trials tell us. AB - Recent clinical trials have refined our understanding of how the glycoprotein (GP) IIb/IIIa inhibitors should best be used. These trials examined whether there are clinical differences between agents, whether empiric use of GP IIb/IIIa inhibitors in acute coronary syndromes is justified, and whether these drugs might allow for early invasive management in acute coronary syndromes. PMID- 11765120 TI - Bioterrorism: an unintended boost to public health? PMID- 11765121 TI - A 62-year-old man with an abnormal electrocardiogram. PMID- 11765122 TI - Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know. AB - Pulmonary alveolar proteinosis (PAP; the accumulation of surfactant lipids and proteins in the alveoli) has a number of infectious and environmental causes but is usually idiopathic. The clinical presentation of PAP is nonspecific; thus, the diagnosis is frequently missed, leading to inappropriate therapy and unnecessary morbidity. Recent advances suggest that a deficiency in granulocyte-macrophage colony-stimulating factor (GM-CSF) activity may lead to this surfactant accumulation. Anti-GM-CSF antibodies have been found in PAP patients, fueling speculation that PAP may be an autoimmune disease. These findings are being translated into novel forms of therapy. PMID- 11765123 TI - When should central venous catheters be changed in the intensive care unit? Should there be a rigid time, based protocol for doing so? PMID- 11765124 TI - Bioterrorism: what practicing physicians can do. PMID- 11765125 TI - Caspases in Huntington's disease. AB - Huntington's disease (HD) is an autosomal dominant condition, resulting from a mutation in huntingtin (htt). Htt is a novel protein, and its normal function is at present not well understood. Nuclear translocation of mutant htt in vitro up regulates expression of the cell death gene caspase-1. We have demonstrated in a transgenic HD mouse model that caspase-1 and caspase-3 are transcriptionally up regulated and activated. Underscoring the relevancy of these findings, recent results suggest that caspase-1 is activated in brains of humans with HD. Caspase activation results in the proteolytic cleavage of key cellular targets, including htt, leading to cell dysfunction. Caspase activation leading to cell dysfunction and death correlates with disease progression. In HD-transgenic mice, caspase inhibition resulted in a delayed onset of symptoms, a slowed progression, and prolonged survival. Caspase inhibition is a therapeutic strategy that merits evaluation in humans with HD. PMID- 11765126 TI - Neuronal dynamics of predictive coding. AB - A critical task of the central nervous system is to learn causal relationships between stimuli to anticipate events in the future, such as the position of a moving prey or predator. What are the neuronal phenomena underlying anticipation? In this article, I review recent results in hippocampal electrophysiology that shed light on this issue. It is shown that hippocampal spatial receptive fields show large and rapid anticipatory changes in their firing characteristics. These changes are experience- and environment-dependent and can be explained by a computational model based on NMDA-dependent synaptic plasticity during behavior. Striking similarities between the anticipatory network dynamics of widely different neural circuits, such as the hippocampus and primary visual cortex, are discussed. These experimental and theoretical results indicate how the microscopic laws of synaptic plasticity give rise to emergent anticipatory properties of receptive fields and behavior. PMID- 11765127 TI - Molecular regulation of circadian rhythms in Drosophila and mammals. AB - Through the use of genetically amenable model systems, we have begun to form a relatively clear idea as to the molecular mechanisms that constitute a functioning circadian clock. It is now known that mechanisms that underlie overt rhythms are conserved across species. At the basic core of the clock lies a transcriptional/translational feedback loop. The primary components of this loop are called clock genes and are similar for the fruit fly, Drosophila melanogaster, and mammalian systems. However, many questions regarding their regulation remain unanswered. In addition to their localization in brain areas associated with pacemaking function, clock genes are also found in peripheral tissues where their presence may confer circadian regulation upon local, tissue specific functions. The light-dark cycle is the primary environmental stimulus for the synchronization of the circadian clock. In Drosophila, light is known to induce the degradation of a clock component resulting in the synchronization of the core clock mechanism. Photic signals are transmitted to the clock, at least in part, by the blue light photoreceptor cryptochrome. Although expression of several mammalian clock gene products is also altered in response to light, the photoreceptor(s) involved have not yet been defined. PMID- 11765128 TI - Galanin: an endogenous anticonvulsant? AB - Galanin is a neuroendocrine peptide involved in the regulation of feeding, pain, sexual behavior, learning, and memory. The recent discovery, that galanin antagonized excitatory glutamatergic neurotransmission in the hippocampus, provided a rationale for its possible antiepileptic effects. Here we summarize the data on the effects of galanin on seizure activity in several animal models of epilepsy. Pharmacological and molecular biological evidence suggest potent anticonvulsant effects of galanin. Exogenous administration of galanin receptor agonists attenuated seizures, whereas application of galanin receptor antagonists potentiated seizure expression. Genetically engineered mice, with either deletion or overexpression of galanin gene, showed altered resistance to seizures, which was in direct correlation with galanin gene expression. Possible mechanisms of the anticonvulsant action of galanin include its effects on synaptic potentiation in hippocampal circuits and inhibition of the release of the excitatory neurotransmitter glutamate from principal hippocampal neurons. PMID- 11765129 TI - Cortical network resonance and motor activity in humans. AB - Large areas of the human motor cortex are devoted to the control of the contralateral hand and forearm. Just how activities scattered across these motor areas may be brought together in the execution of a given movement remains unclear. There is increasing evidence, largely from animal studies, suggesting that sensory integration involves the synchronization of activity between spatially distributed cortical sites. Here we review recent evidence that cortical activity becomes oscillatory and synchronized between spatially distributed sites during performance of a movement in humans. Cortico-cortical synchronization may occur with a precision in the millisecond range, is essentially limited to those cortical elements active in a given task, and changes in both its distribution and frequency in a task-related manner. Synchronization at specific frequencies may therefore link disparate cortical activities into the functional ensembles underlying voluntary movement in humans. PMID- 11765130 TI - Gene therapy with herpes simplex virus vectors: progress and prospects for clinical neuroscience. AB - Gene delivery to the nervous system represents perhaps the ultimate challenge of gene therapy in view of the complexity of this system, the wide variety of intractable neurological diseases, and the need to deliver the gene to nondividing cells. Although a variety of systems for such gene delivery are under development, herpes simplex virus has unique advantages in terms of its large genome size and its ability to naturally enter a latent state in neuronal cells. Considerable progress has been made in the effective disablement of this virus while retaining its ability to deliver genes and in producing long-term expression of the foreign gene. It is likely that these viruses may ultimately be of use in human gene therapy procedures for otherwise intractable neurological diseases such as Parkinson's disease. PMID- 11765131 TI - Neuronal tolerance to O2 deprivation in drosophila: novel approaches using genetic models. AB - In spite of many advances in monitoring oxygenation and preventing cerebro vascular accidents, there is still considerable morbidity and mortality from conditions with cerebral blood flow impairment and O2 deprivation leading to hypoxic/ischemic brain injury. Part of this failure is related to the complexity of the cascade of events that ensue after hypoxia or ischemia, but also part of it may be related to the fact that most research in the previous few decades has focused, justifiably, on cerebral vessel disease. However, an important aspect of the cascade is dependent on many factors that are inherent to the nature and response of the tissue itself. Hence, there is more need now for a two-pronged approach to hypoxic/ischemic brain injury, one focusing on vessel disease, its prevention, and treatment, and the other centering on the brain tissue itself and the factors that render neurons and glia more susceptible or more tolerant to a lack of oxygenation. In the past several years, a number of methods, techniques, and animal models have been used to address the response of neurons and glia to lack of oxygen. In this review, we highlight some novel ideas and some results that we and others have obtained, mostly pertaining to the genetic endowment and responses of the central nervous system to O2 deprivation. The role and importance of genetic models, such as the Drosophila melanogaster, are discussed, and an example illustrating how to harness the power of Drosophila genetics is detailed. PMID- 11765132 TI - The Bristol-Myers Squibb Award for Distinguished Achievement In Neuroscience Research, 2001: H. Robert Horvitz, PhD. PMID- 11765133 TI - Molecular dynamics simulations of the three dimensional model of plasmepsin II peptidic inhibitor complexes. AB - Plasmodium falciparum is a major causative agent of malaria, a disease of worldwide importance. Inhibition of a hemoglobin degrading P. falciparum aspartic protease Plasmepsin II (Plm II) provides a viable strategy for antimalarial therapy. Linear peptidic inhibitors based on the 4(S)-amino-3(S)-hydroxy-5 phenylpentanoic acid at the P1-P1' positions are known which inhibit Plm II with improved selectivity over cathepsin D. A series of computations were performed in order to gain insight into the interactions of these inhibitors with Plm II. The docking and molecular dynamics simulations were performed on a model ligand/enzyme complex to optimize the variables involved in the generation of ligand/enzyme models. This protocol of docking and molecular dynamics (MD) simulation was then used to derive the ligand-enzyme complexes of the molecules used in the present study. Different modes of binding of pepstatin and the three linear inhibitors were studied. Molecular dynamics simulation was performed at 300K for 100ps with a time step of Ifs. The structural effects of ligand binding were analyzed on the basis of hydrogen bond interactions, interaction energies, hydrophobic contacts and RMS deviations in the resulting energy-minimized structures of the receptor-ligand complexes. The results indicate that hydrophobic and hydrogen bonding interactions are responsible for selective inhibition of Plm II and improved selectivity over cathepsin D. Hydrogen bonding interaction plays an important role for amino acid residues such as Asp-34, Asp 214, Thr-217, Ser-218, Val-78, Ser-79, Tyr-192 and Gly-216. The binding of the inhibitors to the enzyme, while producing no large distortions in the enzyme active site cleft, results in significant RMS deviations of the inhibitor, which represent the distortion of the inhibitor, effected by the proteinase. Thus, the information generated from this analysis should be useful for further work in the area of antimalarial research. PMID- 11765134 TI - QSAR of matrix metalloproteinase inhibitor N-[(substituted phenyl)sulfonyl]-N-4 nitrobenzylglycine hydroxamates using LFER model. AB - QSAR analyses of matrix metalloproteinase (MMP) inhibitor N-[(substituted phenyl)sulfonyl]-N-4-nitrobenzylglycine hydroxamates, recently reported by Scozzafava and Supuran, have been attempted using linear free energy related (LFER) model of Hansch to explore the contribution patterns of the phenyl ring substitutions (P1' anchoring site of the ligands) to the activities against MMP 1, -2, -8 and -9 (pC1, pC2, pC, and pC9) and C. histolyticum collagenase (pC(ChC)) and also to find out relations among the activities. Multiple regression analyses applied on the data set reveal that electron withdrawing meta substituents and lipophilic ortho and meta substituents are conducive to pC1 while presence of substituents (larger than hydrogen) at vicinal positions on the phenyl ring and bulkier ortho substituents are detrimental to the activity. Again, the electronic and steric parameters of meta substituents (sigmam and MRm) and lipophilicity parameter of ortho substituents (pio) contribute significantly to pC2, pC8 and pC9: sigmam shows parabolic relationships (optimum sigmam values being 0.518, 0.584 and 0.522 respectively) and steric bulk of meta substituents has negative impact while presence of hydrophilic groups at the ortho positions increases the activities. Further, presence of electron withdrawing meta substituents and hydrophilic para substituents is conducive to the C. histolyticum collagenase (pC(ChC)) activity. The study suggests that the structural and physicochemical requirements of the P1' anchoring site for the activities against MMP-2, -8 and -9 are highly intercorrelated and these are comparatively less correlated with those for the activities against MMP-1 and C. histolyticum collagenase. PMID- 11765135 TI - Synthesis of optically active TAN-67, a highly selective delta opioid receptor agonist, and investigation of its pharmacological properties. AB - We have synthesized the nonpeptidic highly selective delta opioid receptor agonist, (+/-)-TAN-67, (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl 1,2,3,4,4a,5,12,12a-octahydropyrido [3,4-b] acridine. In spite of high potent agonist activity for the delta opioid receptor in in vitro assay, (+/-)-TAN-67 afforded no analgesic activity in the mouse warm-plate test. This result led us to separate (+/-)-TAN-67 into optically pure compounds. Each enantiomer of racemic TAN-67 was synthesized from the corresponding optically active 6 oxodecahydroisoquinoline which was obtained by fractional recrystallization of its optically pure di-p-toluoyl tartaric acid salt. In bioassay using mouse vas deferens, (-)-TAN-67 showed full agonist activity (IC50 = 3.65 nM). On the other hand, (+)-TAN-67 showed almost no agonist activity, but interestingly afforded hyperalgesic activity in vivo (i.t. injection). PMID- 11765136 TI - Synthesis and pharmacological evaluation of analgesic 6-substituted 2(3H) benzothiazolones. AB - A series of novel 6-substituted-2(3H)-benzothiazolones were synthesized and studied as analgesic agents. Among these compounds, two of them were found to exhibit potent analgesic activity in several in vivo tests (acetic acid writhing, Koster, carrageenan and PGE2 hyperalgesia). In these tests the most active compound of this series, i.e. 6-benzoyl-2(3H)-benzothiazolone (4a) was found to be superior to acetylsalicylic acid and equivalent to glafenine. The present study allows to conclude that 4a represents a new type of antinociceptive agent acting in periphery by inhibiting the cyclo-oxygenase pathway and promoting the release of an opioid peptide. PMID- 11765137 TI - Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating phthaloyl and phthalimido moieties. AB - Sulfonamides incorporating 2-carboxy-benzenecarboxamido (phthaloyl) moieties in their molecules were prepared by reaction of phthalic anhydride with aromatic/heterocyclic sulfonamides in mild conditions. Another closely related series of derivatives was prepared by reaction of the same reagents in more energetic conditions, when the corresponding phthalimides were obtained. Some of these compounds showed very good in vitro carbonic anhydrase (CA) isozymes I, II and IV inhibitory properties, with affinities for the enzymes in the low nanomolar range for the best inhibitors. Some of the potent CA inhibitors reported here have been formulated as sodium salts, in aqueous solutions for topical administration as antiglaucoma agents, in normotensive/glaucomatous rabbits. Only the derivatives possessing good water solubility, showed effective and longer lasting topical intraocular pressure (IOP) lowering than dorzolamide and brinzolamide, two clinically used topical antiglaucoma drugs. All the in vivo effective new compounds belonged to the first series of derivatives, whereas the corresponding phthalimides, although stronger in vitro CA inhibitors were devoid of topical IOP lowering properties, probably due to their unproper physico chemical properties. PMID- 11765138 TI - Protein structure-based de novo design and synthesis of aldose reductase inhibitors. AB - Aldose reductase has been implicated in the etiology of diabetic complications. Due to the limited number of currently available drugs for the treatment of diabetic complications, we have carried out a structure-based de novo design and synthesis in an attempt to identify new aldose reductase inhibitors. With the LEGEND program, we have designed 200 chemical structures that fit into the ligand binding site of the crystal structure of the enzyme. After their visual inspection and assessment of synthetic feasibility, four compounds were chosen to be synthesized. These compounds were all found to have reasonable inhibitory activities (IC50 = 17-91 microM), indicating the first successful generation of nonpeptide drug leads that have been obtained using a rational de novo design approach. PMID- 11765139 TI - Differential inhibition of human CYP1A1 and CYP1A2 by quinidine and quinine. AB - 1. The inhibition of recombinant CYP1A1 and CYP1A2 activity by quinidine and quinine was evluated using ethoxyresorutin O-deethylation, phenacetin O deethylation and propranolol desisopropylation as probe catalytic pathways. 2. With substrate concentrations near the Km of catalysis, both quinidine and quinine potently inhibited CYP1A1 activity with [I](0.5) approximately 1-3 microM, whereas in contrast, there was little inhibition of CYP1A2 activity. The Lineweaver-Burk plots with varying inhibitor concentrations suggested that inhibition by quinidine and quinine was competitive. 3. There was only trace metabolism of quinidine by recombinant CYP1A1, whereas rat liver microsomes as a control showed extensive consumption of quinidine and metabolite production. 4. This work suggests that quinidine is a non-classical inhibitor of CYP1A1 and that it is not as highly specific at inhibiting CYP2D6 as previously thought. PMID- 11765140 TI - Enzymatic and non-enzymatic reduction of brucine N-oxide by aldehyde oxidase and catalase. AB - 1. Brucine N-oxide was reduced by aldehyde oxidase in rabbit liver cytosol in the presence of an electron donor, 2-hydroxypyrimidine, under anaerobic conditions. The flavoprotein purified from rabbit liver exhibited significant reductase activity in the presence of electron donors. 2. Brucine N-oxide was also reduced by rabbit liver cytosol and blood in the presence of both a reduced pyridine nucleotide and FAD under anaerobic conditions. The N-oxide reductase activities were inhibited by carbon monoxide and air. However, these activities were not abolished whe n liver cytosol and blood were boiled. Rabbit erythrocytes exhibited the reductase activity, but not plasma. 3. When liver cytosol or blood was separated by DEAE-cellulose column chromatography, the fractions with the reducing activity in the presence of both NADH and FAD also showed catalase activity. 4. Catalase catalysed the brucine N-oxide reduction in the presence of both NAD(P)H and FAD. Hematin also exhibited the reductase activity in the presence of both NAD(P)H and FAD. Photochemically reduced FAD was effective in the reduction instead of NAD(P)H and FAD. 5. Bricine N-oxide reduction proceeds via two routes in liver cytosol and blood. One is enzymatic reduction by aldehyde oxidase; the other is non-enzymatic reduction catalysed by the haem group of catalase in the presence of reduced flavin. PMID- 11765141 TI - Preclinical pharmacokinetics of SB-203580, a potent inhibitor of p38 mitogen activated protein kinase. AB - 1. SB-203580 (4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4 pyridyl)imidazole) is a potent, selective inhibitor of p38 MAP kinase used extensively as a tool inhibitor in various pharmacological and toxicological models. This study was designed to evaluate the pharmacokinetics of SB-203580 in several preclinical species, both to assist with the interpretation of existing studies and to aid in the design of future studies with this inhibitor. 2. In vitro, SB-203580 was stable in mouse, rat, dog, monkey and human plasma over 24 h. However, species differences in plasma protein binding were observed; SB 203580 was 96-97% bound in human plasma and 78-92% bound in other species. These data suggest that protein binding may influence the results of in vitro studies using SB-203580, particularly when comparing results from different in vitro systems that incorporate plasma components. In vivo, SB-203580) demonstrated moderate to high clearance in all species tested, with non-linear elimination observed in the rat at plasma concentrations > 1,000 ngml(-1). Although good solution bioavailability was observed in non-rodents (78% in dog, 32% in monkey), lower and more variable bioavailability was observed in the rat and mouse (3 48%). 3. These interspecies differences in bioavailability, and the non-linear pharmacokinetics observed in rat, highlight the importance of monitoring SB 203580 systemic exposure in parallel witb the pharmacological endpoint during in vivo pharmacology PMID- 11765142 TI - Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans. AB - 1. To determine the ability of fungi to metabolize sulphur- and oxygen-containing azaarenes, Cunninghamella elegans ATCC 9245 was grown in 125-ml flasks containing fluid Sabouraud medium. The cultures and controls were incubated at 28 degrees C with shaking and dosed with 16.7 mM phenothiazine or phenoxazine. After incubation for 72h, the mycelia and filtrates were extracted with ethyl acetate and the combined residues analysed by high-performance liquid chromatography. Residual phenothiazine and phenoxazine were 21 and 22%, respectively, of the total UV absorbance at 254 nm. 2. The metabolites were identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. The fungus oxidized phenothiazine to phenothiazine sulphoxide, 3-hydroxyphenothiazine sulphoxide, phenothiazin-3-one, and 3-hydroxyphenothiazine and oxidized phenoxazine to phenoxazin-3-one. 3. Three of the four compounds produced by C. elegans from phenothiazine were identical to those produced by mammals, supporting the use of the fungus as a microbial model for drug metabolism. PMID- 11765143 TI - Pharmacokinetics and absolute bioavailability of sitafloxacin, a new fluoroquinolone antibiotic, in healthy male and female Caucasian subjects. AB - 1. The aim was to compare the pharmacokinetics of sitafloxacin from a capsule formulation (dose of 500 mg sitafloxacin) and an intravenous (i.v.) formulation infused over 1 h (dose of 400 mg sitafloxacin) in healthy male and female subjects and to estimate the absolute bioavailability of sitafloxacin from the capsule formulation. 2. Following oral administration, sitafloxacin was rapidly absorbed, with a mean maximum concentration in plasma of 4.65 microgml(-1) occuring at median tmax = 1.25 h giving a mean AUC(0-infinity) = 28.1 microg h ml(-1). For the i.v. administration, a mean Cmax = 5.53 microm(-1) occurred at the end of the 1-h infusion with a mean AUC(0-infinity) = 25.4 microg h ml(-1). The mean terminal elimination half-life was 7.0 h (oral) and 6.6 h (i.v.). For the oral and i.v. formulations, the mean total plasma clearance was 296 and 263 mlmin(-1), respectively and the mean volume of distribution was 180 and 150 litres, respectively. 3. Within 48 h post-dose, approximately 61% (range 22-86%) of the administered dose was excreted unchanged in urine following capsule administration, compared with approximately 75% (range 42-101%) following the i.v. formulation. For both formulations, the renal clearance of sitafloxacin (means of 181 and 198 ml min(-1) for the capsule and i.v. doses, respectively) implies active tubular secretion of the drug. 4. The absolute bioavailability of sitafloxacin from the capsule formulation was high at 89%, with a 95% CI of 84 94%. The intersubject variability (CV%) in the sitafloxacin AUC(0-infinity) for the capsule was low at 18.6%. 5. Gender differences in the pharmacokinetics of sitafloxacin were small and would not warrant dose adjustment. 6. The findings show that the capsule formulation offers good oral bioavailability and merits further clinical evaluation of sitafloxacin as an orally effective fluoroquinolone antibacterial. PMID- 11765144 TI - Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man. AB - 1. The absorption, excretion and metabolism of 2-[3-[4-(3-chlorophenyl)-1 piperazinyl]propyl]-4,5-diethyl-2,4-dihydro-3H-1,2,4- triazole-3-one hydrochloride (etoperidone HCl) was investigated in six healthy men. Subjects were tasted overnight before receiving a single oral dose of a 100 mg solution [14C] etoperidone HCl. 2. Plasma (0-48 h), urine (0-120 h) and faecal (0-120 h) samples were collected. The terminal half-life of the total radioactivity from plasma was 21.7 +/- 2.8h with an apparent clearance of 1.01 +/- 0.08 ml min(-1). Recoveries of total radioactivity in urine and faeces were 78.8 +/- 3.6% and 9.6 +/- 4.1% of the dose, respectively. 3. Etoperidone and 21 metabolites were isolated and identified in the plasma, urine and faecal extracts. Unchanged etoperidone accounted for <0.01% of the dose in all excreta samples. Nine metabolites were identified in the plasma extracts and 21 urinary metabolites were identified. Seven faecal metabolites were identified. 4. Five proposed pathways were used to describe the formation of the metabolites: alkyl oxidation, piperazinyl oxidation, N-dealkylation, phenyl hydroxylation and conjugation. Alkyl oxidation of etoperidone resulted in the formation of 2-[3-[4-(3 chlorophenyl)-1-piperazinyl]propyl]-4-ethyl-2,4-dihydro-5- (1-hydroxyethyl)-3H 1,2,4-triazole-3-one. Piperazinyl oxidation of this metabolite leads to the formation of its N-oxide. N-dealkylation of the piperazinyl group led to the formation of 1-(3-chlorophenyl) piperazine and triazole propionic acid. Phenyl hydroxylation led to three important metabolites in the urine and faeces. PMID- 11765146 TI - Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline. AB - In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1% solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 +/- 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits. PMID- 11765145 TI - Topical latanoprost and optic nerve head and retinal circulation in humans. AB - The purpose of the present study was to study the effect of a single instillation of latanoprost on the human optic nerve head (ONH) and retinal circulation. Using laser-speckle tissue blood flow analysis, normalized blur (NB; a quantitative index of tissue blood velocity) was measured every 0.125 sec at a temporal ONH site free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler Imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), endo-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). One drop of 0.005% latanoprost was instilled into one eye and its vehicle into the other in eleven healthy volunteers in a double blinded manner. Measurements of bilateral NB(ONH), CDI parameters, intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were performed before, and 45, 90, 180, and 270 min after instillation. After a single instillation of latanoprost or the vehicle, there was no significant bilateral difference throughout the experimental period. The difference in NB(ONH) between that before and at each time point of measurement (delta NB(ONH)) in the latanoprost-treated eyes was significantly higher between 45 and 270 min after instillation than that in vehicle-treated eyes (P = 0.0003 to 0.0156); ANOVA for repeated measurements also revealed significant difference between both eyes (P < 0.00001). BP, PR, and NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased at least temporarily following a single instillation of topical latanoprost. Although the mechanism of the increase is unclear, the effects of latanoprost on ONH tissue circulation in humans may have clinical implications. PMID- 11765147 TI - Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist. AB - Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects. PMID- 11765148 TI - Studies on receptor binding and signal transduction pathways of unoprostone isopropyl. AB - We examined the binding characteristics of unoprostone isopropyl and its metabolite, M1 (M1), in bovine corpus luteum membranes, mobilization of intracellular calcium in human ciliary muscle cells and cyclic AMP generation in rabbit iris-ciliary body. The ligand binding assay of 3H-unoprostone isopropyl and M1 did not demonstrate any specific binding of these compounds in the bovine corpus luteum membranes. However, there was a high specific binding of prostaglandin F2alpha. Competitive ligand binding studies showed that neither the docosanoid, unoprostone isopropyl, nor M1 binds to prostaglandin receptor sites. In human ciliary muscle cells that express EP1, EP2 and FP receptors, unoprostone isopropyl did not increase the mobilization of intracellular calcium nor was it able to generate cyclic AMP at low concentrations in rabbit iris-ciliary body. Similar observations were made with M1 on the above signal transduction pathways. From these results, it is concluded that unoprostone isopropyl and M1 do not bind to prostaglandin (PG) receptor sites in the bovine corpus luteum membranes and do not have affinity for PG receptors linked to intracellular calcium and cyclic AMP second messenger systems. PMID- 11765149 TI - The use of autologous fibrinogen concentrate in treating ocular hypotony after glaucoma filtration surgery. AB - Antimetabolite therapy with 5-fluouracil (5-FU) or mitomycin-C (MMC) has significantly improved the success rate of glaucoma filtration surgery. However, in some eyes, when filtration is excessive, persistent hypotony may develop. In this study, we describe the experience of using autologous fibrinogen concentrate (AFC) to treat patients with persistent hypotony after glaucoma filtration surgery. Among seven MMC-augmented trabeculectomy patients who developed persistent postoperative hypotony, the effects of AFC intrableb injections were evaluated. Under a microscope, 0.2 ml AFC and bovine thrombin were injected into the blebs of the patients from both sides of the filtering blebs. Postoperative best-corrected visual acuity, anterior chamber status, intraocular pressure (IOP) and fundus examination were followed and compared with those preoperative. On the second day, the mean IOP of seven eyes elevated from preoperative 3.4 +/- 2.1 mmHg to 12.6 +/- 4.2 mmHg, and the anterior chamber became deep without obvious inflammatory response. Within two weeks, macular edema and visual acuity were noted to improve in six eyes (85.7%). In addition, after a mean follow-up of 25 months, the trabeculectomy procedure remained successful in all eyes. AFC appears to be safe and effective in the treatment of ocular hypotony after glaucoma filtration surgery. PMID- 11765150 TI - Induction of cellular toxicity in cultured porcine corneal keratocytes by endothelin-1. AB - The effect of endothelin-1 (ET-1) on corneal cells is not well understood. We investigated the biochemical changes of cultured porcine corneal keratocytes under exposure to ET-1. The results indicate that ET-1 has remarkable effects to inhibit corneal keratocytes on 3H-thymidine, 3H-leucine, 3H-uridine uptakes and cellular migration. It is in a dose-dependent manner at concentrations ranging from 10(-7) M to 10(-9) M. The 50% inhibitory dose (ID50) for ET-1, as measured by 3H-thymidine uptake, 3H-uridine uptake and 3H-leucine uptake, were 10(-7) M, 10(-0.52) M and 10(-11.8) M, respectively. The dead and living cells were estimated with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay that was converted tetrazolium dye of living cells only into insoluble purple formazan crystals within mitochondria. In the presence of ET-1, the cellular MTT values were also decreased. The ID50 for ET-1 with cell migration assay and MTT assay were measured at 10(-7.86) M and 10(-5.1) M. Endothelin-1 (10(-6) M) promptly changed cellular morphology and attenuated adhesion observed with laser scanning cytometer. Endothelin-1-induced characteristic apoptosis cells were observed using a TUNEL assay that detected fragmented DNA of apoptosis. Western blot assay revealed that endothelin-1 induced proteolysis and decreased in fibronectin protein. These findings indicate that endothelin-1 may lead keratocytes to death resulting from induction of apoptosis and functional loss. PMID- 11765151 TI - Probing anterior segment kinetics with focally applied mydriatics. AB - The purpose of this study was to examine the effects of convectional flow and anterior segment configuration on drug kinetics. Mydriatics were applied focally at the limbus in order to produce sector dilation of the pupil. Subjects were tested with either tropicamide or phenylephrine, applied at the superior, temporal, inferior, or nasal limbus (or as a conventional drop). Changes in pupil form were analyzed by means of photography, digitization, and circular Fourier series representation. Both tropicamide and phenylephrine were found to produce sector dilation; however, phenylephrine was approximately twice as effective. Applications at the superior limbus were significantly less effective than applications at the inferior limbus. The results are interpreted in terms of anterior segment convectional flow, which is believed to play a substantial role in pharmacokinetics of the anterior segment. PMID- 11765152 TI - Determination of aldose reductase activity in the eye by localized magnetic resonance spectroscopy. AB - The polyol pathway plays an important role in the formation of diabetic complications of the eye. Due to variations in the pharmacokinetic properties of aldose reductase inhibitors and variations in the degradation of the blood-ocular barrier, it is often difficult to determine the proper intraocular levels of aldose reductase inhibitor required for inhibition of aldose reductase activity in ocular tissues. Utilizing localized magnetic resonance spectroscopy (MRS), the present method can determine adequate inhibition of aldose reductase activity in the lens by noninvasively measuring polyol pathway activity in the eye. New Zealand White rabbits, under anesthesia, were administered an intravitreal injection of 3-fluoro-3-deoxy-D-glucose (3FDG). Localized MRS was then used to assess polyol pathway activity by determining the levels of 3-fluoro-3-deoxy-D sorbitol (3FS) and 3-fluoro-3-deoxy-D-fructose (3FF) metabolite formation from 3FDG in the eye. MRS was able to follow the loss of 3FDG from the vitreous into the anterior segment of the eye and particularly into the lens and aqueous. The primary metabolism of 3FDG observed by MRS was the formation of 3FS in the lens that is catalyzed by aldose reductase. Production of 3FS was linear in time and decreased with the oral administration of an aldose reductase inhibitor. PMID- 11765153 TI - Ocular pharmacokinetics of cephalosporins using microdialysis. AB - The purpose of this study was to delineate the ocular pharmacokinetics of cephalosporins and investigate the presence of peptide transporters in the retina. New Zealand albino rabbits were kept under anesthesia. A concentric microdialysis probe was implanted in the vitreous chamber and linear probe across the cornea in the aqueous humor. Isotonic phosphate buffer saline was perfused through the probes, and samples were collected every 20 min over a period of 10 hr. A 500 microg dose of cephalexin, cephazolin, and cephalothin was administered intravitreally. Inhibition experiments were carried out in vivo, using gly-pro and gly-sar. The vitreal half-lives of cephalexin, cefazolin, and cephalothin were 185.38 +/- 27.25 min, 111.40 +/- 17.17 min, and 146.68 +/- 47.52 min, respectively. Cephalexin generated higher aqueous humor concentrations compared to cefazolin. The pharmacokinetic parameters of cephalexin in the presence of gly pro, i.e., AUC (44452.06 +/- 3326.55 microg x min/ml), clearance (0.0013 +/- 0.0004 ml/min) and vitreal half-life (825.12 +/- 499.95 min) were different from that of the control (14612.83 +/- 4036.47 microg x min/ml, 0.0036 +/- 0.0011 ml/min, and 187.96 +/- 65.12 min, respectively). Gly-pro did not inhibit cefazolin, and gly-sar showed no effect on the pharmacokinetics of both drugs. These studies indicate the involvement of a peptide carrier in the transport of cephalosporins across the retina. Although gly-pro inhibited the elimination of cephalexin from the vitreous, the effect of an alpha-amino group on peptide carriers was not clearly evident. PMID- 11765154 TI - Clinical outcomes of consanguineous marriages in Turkey. AB - Turkey has a high rate of consanguineous marriages. Different nationwide surveys indicate that today 20-25% of marriages are consanguineous, with the rate having increased over the last 15 years. The results of many studies show that the rate of consanguinity among parents of children with rare recessive diseases is quite above Turkey's average and that the high consanguinity rate is one of the underlying factors of high infant and child mortality and fertility in Turkey. PMID- 11765155 TI - Fiberoptic phototherapy versus conventional daylight phototherapy for hyperbilirubinemia of term newborns. AB - The efficacy and wavelengths of fiberoptic phototherapy and conventional daylight phototherapy were compared in a relatively larger series of term newborns with nonhemolytic and significant hyperbilirubinemia than reported in previous studies. One hundred and nine term newborns were randomly assigned to receive either fiberoptic phototherapy on a fiberoptic phototherapy pad or overhead conventional phototherapy consisting of five daylight fluorescent lamps. Although the average spectral irradiance measured during the study period was significantly greater in the fiberoptic phototherapy group (9.2+/-1.2 microW/cm2/nm vs 7.1+/-1.1 microW/cm2/mm, p < 0.05), conventional phototherapy was significantly more effective in decreasing bilirubin levels: the duration of exposure to phototherapy was significantly shorter (49.4+/-14.4 hours vs 61+/ 13.1 hours, p < 0.05), and overall bilirubin decline rate as mg/dl/h and percent/h was significantly greater in the conventional phototherapy group (0.15+/-0.06 mg/dl/h vs 0.11+/-0.05 mg/dl/h, and 0.81+/-0.34 percent/h vs 0.60+/ 0.28 percent/h, p < 0.05). There were four failures of phototherapy in the fiberoptic phototherapy group whereas no phototherapy failure was observed in the conventional phototherapy group (p < 0.05). The emission spectrum of the daylight fluorescent lamp revealed a broad emission between the violet and red spectra with tiny narrow peak emission bands in 405 nm, 436 nm, 546 nm and 577 nm, while a broad emission through the blue and green wavelengths (mainly in the green spectrum) without any peak emissions was detected in the tungsten-halogen lamp of the fiberoptic phototherapy system. Conventional phototherapy with daylight fluorescent lamps should be preferred to fiberoptic phototherapy administered with fiberoptic phototherapy and in the treatment of term newborns with nonhemolytic hyperbilirubinemia. PMID- 11765156 TI - Prevalence of asthma and other allergic disorders among schoolchildren in Diyarbakir, Turkey. AB - This study was performed to describe the prevalence rates of allergic diseases among children in southeast Anatolia. A questionnaire survey of children six to 15 years old was conducted using a modified version of the Turkish translated ISAAC protocol, with additional questions concerning sociodemographic and environmental characteristics of children that could be potential risk factors for allergic disorders. Questionnaires were distributed to parents of all children aged below 11 years and to children themselves aged over 11 for completion. A total of 3,040 children returned the questionnaires. The lifetime prevalence rates of asthma, wheezing, allergic rhinitis and atopic dermatitis were 14.1%, 22.4%, 12.9%, and 7.8%, respectively. The prevalence of wheezing, rhinitis and chronic rash in the last 12 months were 14.7%, 39.9%, and 11.8%, respectively. The prevalence rates of symptoms and diagnoses of allergic disorders were similar in boys and girls. Passive smoking, pet ownership, number of household and socioeconomic status were not significant risk factors for allergic diseases. Family history of atopy was the most prominent risk factor for all types of allergic diseases, high prevalence rates of asthma, rhinitis and eczema exist among schoolchildren in southeast Anatolia. PMID- 11765157 TI - Atrial septal aneurysm in children. AB - Atrial septal aneurysm (ASA) has rarely been described in children. In this study, we evaluated the incidence and natural course of this anomaly in children. ASA was found in 30 patients (1%); 16 patients had type 1R and 14 patients had type 2L ASA. Twenty patients with ASA were followed: in four the ASA disappeared and in three patients with type 2L an atrial septal defect (ASD) developed during follow-up. The most common associated lesion was patent foramen ovale (PFO). We conclude that ASAs in children are not rare lesions, and that these aneurysms, particularly type 2L aneurysms, should be followed for occurrence of ASD. PMID- 11765158 TI - A study of the prevalence of having fractures and the affecting factors in young male adults throughout childhood and adolescence. AB - Injuries due to accidents in children and adolescents, who are more sensitive to different risk factors in their social and physical environments, play an important part in mortality and morbidity. Fractures are the most commonly seen problems among these injuries. This cross-sectional study was carried out in a two-year vocational military school in Ankara between 1-10 May 2000. All, 2720 students in the school were included and data were collected via a questionnaire distributed to the students. It was found that 418 (17%) out of 2,461 students we could interview had had a fracture. No statistically meaningful relationship was found between the frequency of having fractures and the educational status of the parents or employment status of the mother. However, it was seen that the frequency of fractures increased as the economical status of the parents increased. The high frequency of fractures in childhood and adolescence in young males, and the traditional practice of going to unlicensed and medically untrained adults, and "bonesetters" (27% of those surveyed) are two important findings that should be taken into consideration. PMID- 11765159 TI - Height prognosis in children with late-diagnosed congenital hypothyroidism. AB - It is a general belief that early and adequate thyroid hormone replacement achieves normalization of growth as well as disappearance of clinical sings and symptoms of hypothyroidism. Due to the lack of comprehensive growth studies, height prognosis has remained controversial in late-diagnosed hypothyroidic children. The limited number of previous studies have suggested permanent height deficit in these children. In this study we present longitudinal growth and final height of 20 children (14 females and 6 males) in whom the duration of hypothyroidism before onset of therapy varied from three to 12.6 years. The etiological distribution of cases revealed ectopic thyroid tissue in nine cases, agenesis in seven, and dyshormonogenesis in four cases. At the time of the diagnosis all hypothyroidic children had severe growth retardation (mean height SDS +/- SD -3.95+/-1.07) due to prolonged hypothyroidism. Although the catch-up spurt corrected an important part of the initial height deficit in all patients, only nine patients reached or exceeded their target height, and the final height of five patients remained below 2 SD of mean. Despite treatment, prolonged hypothyroidism may result in compromised adult height in some patients. The contributing factors to this height deficit may include the duration of hypothyroidism, the height deficit at the time of the diagnosis, etiological differences and the diminished potential for catch-up growth in late-diagnosed hypothyroidism. PMID- 11765160 TI - Low plasma apolipoprotein A-I level: new prognostic criterion in childhood cirrhosis? AB - Apolipoprotein A-I (apo A-I) has been found to be decreased in adults with cirrhosis, but it has not been routinely used for prognostic purposes thus far. This study was performed to determine apo A-I levels in childhood cirrhosis and to establish some prognostic cut-off values. Apo A-I levels of 78 children with chronic liver disease, 38 of whom had cirrhosis as well, were studied. Mean values of cirrhotic, non-cirrhotic and healthy children were not different (p > .05). However, in cirrhotic children, the highest value was detected in the Child Pugh A group, and it was different from those of the B and C groups (p < .05 and p < .001, respectively). Apo A-I was the lowest in the moderate risk group of Malatack's model, and was significantly different from the low risk group (p < .05). Apo A-I was inversely correlated with Malatack score, Child-Pugh score, total bilirubin, conjugated bilirubin, and prothrombin time (p < .01, p < .01, p < .01, p < .01, p < .05, respectively). In cirrhotic children with cholestasis, apo A-I was lower than in non-cholestatic children (p < .05). Apo A-I value < 80 mg/dl had 84% specificity and 84% negative predictive value for the high risk group of Malatack's model. Similarly, Apo A-I value < 83 mg/dl had 95% specificity and 87% negative predictive value for the Child-Pugh C group. We concluded that Apo A-I is a sensitive and specific parameter of poor prognosis in childhood cirrhosis. PMID- 11765161 TI - The role of heterotopic gastric mucosa with or without colonization of Helicobacter pylori upon the diverse symptomatology of Meckel's diverticulum in children. AB - The roles of heterotopic gastric mucosa either with or without colonization of Helicobacter pylori (HP) upon the diverse symptomatology of Meckel's diverticulum (MD) in children have been evaluated retrospectively. The medical records of 92 patients who underwent MD excision either incidentally or symptomatically between 1976 and 1997 were reviewed retrospectively. Age at admission and symptoms were recorded. The slides were stained with hematoxylin eosin and Giemsa to identify the presence of heterotopic tissue, ulceration, hemorrhage, inflammation and HP. Bleeding, obstruction and inflammatory groups were statistically compared with chi-square test. The age of the patients ranged between 1 day and 14 years with a mean of 3.5+/-3.8 years. The male: female ratio was 3.6:1. Among 92 MD, 18 (19.5%) were remove incidentally, one of which had heterotopic gastric mucosa. The indications fo surgical removal of MD were intestinal obstruction, diverticulitis and bleeding in 45 (48.9%), 11 (11.9%) and 18 (19.5%) patients, respectively. Heterotopic gastric mucosa was detected in 28 (30.4%) patients, of whom 8, 3, and 16 presented with intestinal obstruction, diverticulitis and bleeding, respectively. Helicobacter pylori was not detected in one patient with incidental removal of MD; with heterotopic gastric mucosa however, three patients with obstruction, one patient with diverticulitis and one patient with bleeding had HP in the heterotopic gastric mucosa located in MD. MD may become symptomatic due to a complicated course such as rectal bleeding, intestinal obstruction or diverticulitis. The presence of heterotopic gastric mucosa in MD seems to mainly associate with rectal bleeding. The presence of HP colonization in heterotopic gastric mucosa does not increase the incidence of rectal bleeding. The other complications of MD, including intestinal obstruction and diverticulitis, are not directly related to the presence of heterotopic gastric mucosa in the MD. However, colonization of heterotopic gastric mucosa by HP seems to increase the incidence of these complications. PMID- 11765162 TI - Estimation of pulmonary artery pressure by contrast-enhanced Doppler signals and comparison with catheter-measured pressures. AB - Determination of pulmonary artery systolic pressure (PASP) is essential for the diagnosis, and the timing and type of management of patients with congenital heart disease (CHD). Usually cardiac catheterization, an expensive and invasive technique, is required for accurate measurement. A number of noninvasive methods for the assessment of PASP have been developed, one of which is estimation of PASP using contrast-enhanced tricuspid regurgitation Doppler signals (TRDS). In this study, right ventricular systolic pressures (RVSP) and PASP of 36 patients (19 girls, 17 boys; aged 5 months to 15 years) with CHD were estimated by TRDS before and after galactose solution (GS) and were compared with catheterization measurements. Significant TRDS (> 1 m sec.) were obtained in nine of 36 (25%), patients before GS and in 23 of 36 patients (64%) after GS. TRDS were increased significantly by contrast agent. Estimated RVSP and PASP were significantly different from the measured pressures before and after GS. There were significant correlations between the estimated RVSP and PASP and measured RVSP after GS. Estimated pressures were underestimated. We conclude that it is better to use the estimated PASP on patients with significant TRDS for the classification of PASP. PMID- 11765163 TI - An open trial and discontinuation study of fluoxetine in children and adolescents with obsessive-compulsive disorder. AB - The purpose of this study was to examine the efficacy and safety of fluoxetine for short-term and long-term treatment in children and adolescents with obsessive compulsive disorder (OCD). Twenty-three children and adolescents (mean age 12.0, SD = 2.3) treated with fluoxetine for OCD with or without Gilles de la Tourette's syndrome were the subjects of this study. The design was an open-label trial for 20 weeks of fixed-dose fluoxetine (20 mg/day). OCD symptom severity was measured with the Maudsley OCD scale and with Clinical Global Impression Scale (CGI). All of the patients were followed-up after discontinuation of the drug for 24 months. Patients with OCD showed a significant decrease in the severity of their OCD symptoms according to Maudsley OCD scores (p < 0.001) and CGI scores (p < 0.001). Fluoxetine was generally well tolerated, and side effects were relatively mild. Ten patients (43.5%) with OCD who responded to fluoxetine relapsed in the follow up period, but responded well to fluoxetine. These results indicate that fluoxetine is effective and safe for short-term and long-term treatment of OCD in children and adolescents. PMID- 11765164 TI - Severe hemolytic anemia after repair of primum septal defect and cleft mitral valve. AB - Two cases are described in which severe mechanical hemolytic anemia developed after surgical repair of primum atrial septal defect (ASD) and cleft mitral valve. In both cases there was residual mitral regurgitation after repair. Moderate mitral regurgitation and collision of the regurgitant jet with the teflon patch used for repair of the primum ASD were detected by color-Doppler echocardiography imaging. Laboratory tests showed normochromic normocytic anemia, increased indirect serum bilirubin, decreased plasma haptoglobin and hemoglobinuria. The peripheral blood smear contained numerous fragmented red cells. Following another surgical correction of the mitral valve (repair or mitral valve replacement), there was no more hemolysis. The two presented cases show that foreign materials in association with localized intracardiac turbulence may cause severe hemolysis. PMID- 11765165 TI - Pulmonary arteriovenous fistula in the newborn: a case report of Rendu-Osler Weber syndrome and a review of the literature. AB - In most instances, congenital arteriovenous fistula is only one manifestation of a more widespread abnormality; 60% of patients also have hereditary hemorrhagic telangiectasis (Rendu-Osler-Weber syndrome). Among those with congenital pulmonary arteriovenous fistula, the diagnosis is made during infancy in only 15% of patients. We present a case of pulmonary arteriovenous fistula in a newborn and review the literature. This rare condition of newborns can be treated with different surgical procedures. Only 17 cases of newborn pulmonary arteriovenous fistula/have been reported, and only two of those had associated Rendu-Osler Weber syndrome. The results of surgical procedures were good in most of these cases. We treated our case with lobectomy successfully. PMID- 11765166 TI - Giant cell pneumonia in a leukemic child in remission: a case report. AB - Giant cell pneumonia is a rare and uncommon type of lung infection developing as a complication of measles, especially in immunocompromised patients, whether their immune systems are affected primarily or whether they have acquired immune defects. As well as being uncommon, it is also atypical because of absence of the characteristic rash and of absent or low antibody titers against measles in most of the cases. It is known that cellular immunity is more important than humoral immunity in the host response to measles, so hypogammaglobulinemic patients with normal cellular immunity usually recover uneventfully from measles and also have the characteristic rash. We report a case with giant cell pneumonia that was confirmed by postmortem histopathological examination. We especially want to point out that even in the absence of rash, with the clinical and radiological features of pneumonia, measles should be considered in a patient, whether in remission or not, receiving immunosuppressive treatment. PMID- 11765167 TI - Intraperitoneal involvement in rhabdomyosarcoma CT findings in a child. AB - Intraperitoneal neoplastic involvement in rhabdomyosarcoma is rare and its incidence and imaging characteristics need to be further described. We present the computerized tomography (CT) findings of a case with pelvic rhabdomyosarcoma and intraperitoneal neoplastic involvement. Enhanced peritoneal and retroperitoneal masses were seen around the liver, spleen, in the paracolic gutters, and in the lesser sac without evidence of ascites, mesenteric nodules or omental caking. Our case also showed that absence of ascites does not preclude the presence of peritoneal involvement. Progression in the peritoneal disease was also well demonstrated by CT. PMID- 11765168 TI - Prenatal echocardiographic diagnosis of situs inversus totalis and transposition of the great arteries: a case report. AB - A case of situs inversus totalis and transposition of the great arteries (TGA) was diagnosed prenatally at 25 weeks' gestation. Postnatal echocardiographic examination confirmed the antenatal findings. This case underscores the importance of recognizing situs abnormalities during obstetric and fetal echocardiographic examination, as they are often associated with cardiac anomalies. Accurate prenatal diagnosis of structural heart defects is extremely important in family counselling and in planning obstetric and postnatal treatment. PMID- 11765169 TI - A case of Sandifer's syndrome with hand tremor. AB - A 1.5-month-old boy with Sandifer's syndrome is described. After an uneventful delivery, he presented torticollis, seizure-like dystonic neck movements usually associated with feeding, episodic vomiting, inspiratory stridor and hand tremor in the first month of life. Barium esophagogram demonstrated gastroesophageal reflux, for which medical therapy was started. Children with torticollis and dystonic movements should be evaluated for Sandifer's syndrome. Early diagnosis and treatment of gastroesophageal reflux may prevent complications. PMID- 11765170 TI - Two male patients with nevoid basal cell carcinoma syndrome from Turkey. AB - Nevoid basal cell carcinoma syndrome, also known as Gorlin's syndrome, is a familial autosomal dominant syndrome characterized by multiple basal cell carcinomas, multiple odontogenic keratocysts of the jaws, and skeletal anomalies. Both tumors and malformations of the central nervous system occur with nevoid basal cell carcinoma. Medulloblastoma is the primary brain tumor most frequently associated with this syndrome. The authors report in this article two male patients with nevoid basal cell carcinoma syndrome: a 22-year-old male patient with multiple odontogenic keratocysts, who had medulloblastoma at two years and multiple basal cell carcinoma at 10 years of age, and a 15-year-old male patient with skeletal abnormalities and multiple odontogenic keratocysts in the jaws. PMID- 11765172 TI - Familial microtia in four generations with variable expressivity and incomplete penetrance in association with type I syndactyly. AB - Familial microtia with external ear canal atresia and conductive deafness is rarely reported. Autosomal dominant and recessive inheritance have been suggested depending on various family reports. Cases with other malformations in addition to microtia have been described, although the microtia generally is an isolated finding. Here we report a family with microtia, external auditory canal atresia and conductive deafness in four generations. The mode of inheritance of the disease was autosomal dominant within this family. Also, variable expressivity, incomplete penetrance and generation skipping are evident in the pedigree. Association of microtia with type I syndactyly, which has never been reported previously, was present in the index case. PMID- 11765171 TI - Familial arthropathy with camptodactyly: reports of two families. AB - Familial association of congenital camptodactyly and arthropathy without evidence of concurrent inflammation has an autosomal recessive pattern of inheritance. We describe four children born to consanguineous parents in two families with congenital camptodactyly and polyarthropathy which were misdiagnosed and treated as juvenile rheumatoid arthritis (JRA) for some time. The siblings in the second family also had fibrosing pleuritis. Histopathological examination of the synovial tissues of the children in the first family revealed synovial hypertrophy and presence of multinucleated giant cells with minimal inflammation and vasculitis. On the other hand, prominent fibrosis with no inflammation was present in the synovial tissue of the elder boy in the second family. Thus, while the children in the first family had the phenotypic characteristics of congenital familial hypertrophic synovitis, the latter siblings probably represent a form of the familial fibrosing serositis. PMID- 11765173 TI - A new case of Balci's syndrome (corneal opacity, microphthalmia, microcephaly, mental retardation, and generalized muscular spasticity associated with congenital heart disease). AB - The association of corneal opacity, microphthalmia, microcephaly, mental retardation, and generalized muscular spasticity with hyperglycinemia was presented for the first time by Balci and colleagues in 1974. After this report, some similar cases in the literature were referred to as Balci's syndrome. In this paper we describe a new case of Balci's syndrome, a 2.5-month-old female patient with corneal opacity, microphthalmia, microcephaly, mental retardation, and generalized muscular spacticity. All of these findings are acceptable as Balci's syndrome, and in addition she had congenital heart disease (ventricular septal defect) and renal anomalies. In this paper other syndromes associated with corneal opacity and mental retardation are discussed. PMID- 11765174 TI - Nuclear medicine advances in breast cancer imaging. AB - Primary breast cancer imaging can be done by various means. Mammography is the most widely used technique because of its excellent diagnostic performance, patient compliance, and cost-effectiveness ratio. Other radiological techniques (such as ultrasonography) are indicated in particular circumstances, while some (such as digital mammography and magnetic resonance imaging) seem very promising but are still under evaluation. The recent technological progress in nuclear medicine has resulted in the availability of two diagnostic procedures that have been validated by extensive international clinical experience: scintimammography with Sesta-MIBI and positron emission tomography (PET) with fluorodeoxyglucose (FDG). The general advantage of nuclear medicine imaging is that tumor-seeking radiopharmaceuticals accumulate in cancer lesions, which makes scintimammography and PET fundamentally different from the radiological techniques that image the tumor mainly on the basis of morphological alterations. Scintimammography is indicated for the study of breast lesions in patients in whom mammography is non diagnostic or difficult to interpret; it may be useful also to assess and even predict the response to primary chemotherapy. FDG-PET is increasingly used in oncology and is particularly useful in breast cancer as it gives more accurate information than scintimammography in the evaluation of patients with ambiguous mammographies and in discriminating between viable tumor, fibrotic scar or necrosis following surgery, chemo- or radiotherapy. The FDG uptake in the tumor correlates with the histological grade and potential aggressiveness of breast cancer, which may have prognostic implications. In addition to its usefulness in the study of breast lesions, FDG-PET shows great efficacy in detecting lymph node involvement prior to surgery. Whole-body PET provides information on soft tissue and bone metastases in a single scanning session, and has an important clinical role in detecting recurrent metastatic disease. On the basis of the above mentioned evidence, nuclear medicine techniques, integrated with radiological techniques, offer an interesting opportunity to improve the diagnostic imaging yield in breast cancer, which will eventually lead to better patient management. This paper reports on the latest developments in this field. PMID- 11765175 TI - Trends in skin cancer incidence in Neuchatel, 1976-98. AB - AIMS AND BACKGROUND: Limited data are available on trends in skin cancer incidence. This paper examines trends of the three major histotypes of skin cancer in an environment favorable for skin cancer registration. METHODS: Trends of skin cancer incidence by histotype in the Swiss Canton of Neuchatel (165,000 inhabitants) were analyzed on the basis of 4,455 incident cases of basal cell, squamous cell carcinoma, and malignant melanoma registered over the period 1976 1998. RESULTS: Trends over the last decade considered tended to be downwards for squamous cell carcinoma in both sexes, were still on the rise for basal cell carcinoma, and leveled off for malignant melanoma in both sexes. CONCLUSIONS: Different trends were confirmed in this population between skin cancer histotypes related to cumulative intense sun exposure (squamous cell carcinoma) and those mainly related to more complex patterns of exposure to sunlight (basal cell carcinoma and malignant melanoma). PMID- 11765176 TI - Cancer mortality in Italy, 1997: quantifying the fall in rates in women and men. AB - AIMS AND BACKGROUND: To update data and statistics on cancer death certification in Italy to 1997. METHODS: Data and statistics for 1997 subdivided into 31 cancer sites are presented. Trends in age-standardized rates for major cancer sites are plotted from 1955 to 1997. RESULTS: The age-standardized (world standard) death certification rates from all neoplasms steadily declined from the peak of 199.2/100,000 males in 1988 to 174.7 in 1997 and for females from 102.5 to 93.0. The decline was larger in truncated rates, by about 26% for males since 1983 and by 24% for females since the top rate of the early 1960's. A major component of the favorable trend in males was lung cancer, which showed a 16% decline from the peak of 1987-88, to reach 50.6/100,000 in 1997, corresponding to about 5,000 avoided deaths. The decline in lung cancer was about 34% at age 35 to 64. For females, in contrast, both the absolute number of lung cancer deaths and the age standardized rate of 7.9/100,000 were among the highest values ever registered, reflecting the different pattern of spread of the tobacco-related lung cancer epidemic in the two sexes. Intestinal cancer rates were stable for males but declined by approximately 10% for females, mostly in middle age, as did breast cancer mortality. Among neoplasms showing favorable trends, there were other tobacco-related neoplasms in men, plus the continuing fall in stomach and cervix uteri. Upward trends were observed for non Hodgkin's lymphomas. CONCLUSIONS: The fall in cancer mortality observed over the last decade in Italy is attributable to a decline in lung and other tobacco-related neoplasms in males, together with a persistent fall in stomach and uterine (cervical) cancer. In women, there were also recent falls in intestinal and breast cancer rates, and declines in both sexes in rarer neoplasms influenced by therapeutic advancements. PMID- 11765177 TI - Single-agent chemotherapy with vinorelbine for pretreated or metastatic squamous cell carcinoma of the esophagus. AB - AIMS AND BACKGROUND: At least half of the patients with squamous cell carcinoma of the esophagus (SCCE) present at diagnosis with metastatic disease, and most patients in a locally advanced phase will develop metastases despite potentially curative local therapy. Thus, the majority of patients with SCCE will become candidate for palliative chemotherapy. Only a few drugs have demonstrated moderate activity (>15%) against SCCE. The main purpose of this phase II trial was to assess the activity of vinorelbine, a semisynthetic vinca alkaloid with a wide spectrum of action, in advanced or relapsed SCCE. METHODS: Seventeen patients were included in the trial. Eleven of them had already received chemotherapy (cisplatin and fluorouracil) and/or radiotherapy at the time of the first diagnosis. All patients were treated with vinorelbine at the dose of 30 mg/m2 every two weeks. RESULTS: Sixteen of the 17 patients enrolled in the trial were assessable for activity: partial responses were observed in 4 of the 16 (25%), and 3 of them were pre-treated patients. A significant improvement of dysphagia was obtained in 4 of 11 symptomatic patients. Toxicity was mild, with only one episode of grade 4 neutropenia and constipation. CONCLUSIONS: In our experience, single-agent vinorelbine is active against SCCE. It was also active in patients previously treated with cisplatin and fluorouracil. The good tolerability and the possibility of relieving symptoms such as dysphagia strongly suggest the addition of vinorelbine to combination regimens with cisplatin as front-line chemotherapy for SCCE. PMID- 11765178 TI - Leucovorin + 5-fluorouracil plus dipyridamole in leucovorin + 5-fluorouracil pretreated patients with advanced colorectal cancer: a pilot study of three different dipyridamole regimens. AB - Dipyridamole, an inhibitor of nucleoside transport, increases the activity of 5 fluorouracil in a dose-dependent manner. The purpose of the present study was to determine whether dipyridamole with 5-fluorouracil and leucovorin gave an improved therapeutic outcome. Sixty patients entered in the present pilot study had previously received 5-fluorouracil (450 mg/m2) and leucovorin (100 mg/m2), every week, and relapsed during this treatment, which ended at least 6 weeks prior to study entry. Dipyridamole was administered at three different dosing schedules (DS) and methods of administration in three groups of patients. DS I: dipyridamole, 30 mg/m2 in normal saline solution, in 90 min iv infusion, followed by leucovorin, 100 mg/m2 iv push, followed by 5-fluorouracil, 450 mg/m2 in normal saline solution, in 60 min iv infusion, dipyridamole tablets (75 mg) every 12 hrs, continuously during the time of chemotherapy. DS II: dipyridamole, 50 mg/m2 in normal saline solution, in 90 min iv infusion, and the rest was the same as DS I. DS III: without oral dipyridamole, patients received dipyridamole (50 mg/m2) iv in the same manner as in DS I and II. Treatment was continued until tumor progression or unacceptable toxicity. All patients (n = 60) entered in the present study were assessable for response and toxicity. No complete response was observed. No patient at DS I responded, whereas 2 patients at DS II and 3 at DS III had a partial response (P <0.1). Stable disease was found with DS I (n = 1), DS II (n = 8) and DS III (n = 9) (P <0.01). More patients progressed at DS I (n = 19) than at DS II (n = 10) and DS III (n = 8) (P <0.0007). The median duration of response was 11 weeks (range, 8-16). Time to progression was 17 weeks for DS I, 15 weeks (range, 10-19) for DS II, and 14 weeks (range, 11-21) for DS III (P = 0.43). Median survival did not differ significantly between DS I (29 weeks; range, 14-48), DS II(31.5 weeks; range, 17-63) and DS III (36 weeks; range, 16 58) (P = 0.2). Neutropenia was most severe with DS I (grade 2, P<0.01) and DS II (grade 1, P<0.05) and nausea/vomiting with DS I (grade 0, P < 0.0005, grade 1, P <0.0002, grade 2, P <0.02) and DS III (grade 3, P<0.0009). Diarrhea was most severe in DS II (grade 3, P <0.005). Mucositis was increased in DS II (grade 0, P <0.008), anorexia in DS II (grade 0, P <0.032) and fatigue in DS I (grade 0, P <0.003). More patients in DS I than with the other two DS experienced headache (P <0.044). According to the response achieved at DS III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS (except for nausea and vomiting grade 3, P <0.009), it can be stated that DS III is the appropriate dose and the simplest schedule of administration (administration of dipyridamole during therapy only). In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies. PMID- 11765179 TI - Long-term infusional systems: complications in cancer patients. AB - Long-term central vein catheters have found clinical application in different fields of medicine and particularly in oncology. In fact, the continuous infusion of some drugs has become the standard treatment in a wide variety of cancers, but central vein catheters are not without risks. The authors report their experience with central vein catheters. From January 1,1998, to December 31, 1999, 98 central vein catheters were placed in neoplastic patients. Seventy-seven (78.6%) Groshong and 16 (16.3%) Port-a-cath catheters were used. The central vein catheters were placed under local anesthesia. Before placement of the central vein catheters, the patients were checked by chest X-ray and neck ultrasonography. The procedure was performed under fluoroscopic control. The central vein catheters were flushed periodically with normal saline solution and sodium heparin. Sterile transparent adhesive dressings were used to occlude the operative site. The median follow-up of patients was 9 catheter months (range, 1 24 months). There were a few early and late clinically evident complications. The early complications were dislodgement in 5 cases (5.1%). The late complications were: fibrin sleeve in 1 case (1.1%), thrombosis in 2 cases (2.1%) and skin infection in 4 cases (4.1%). The low prevalence of major complications related to implants and management of these supports an increased use in oncology. PMID- 11765180 TI - Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: a retrospective single institution's study. AB - AIMS AND BACKGROUND: [corrected] The purpose of the study was to analyze the long term follow-up of a single institution's experience with a regimen of concomitant carboplatin + 5-fluorouracil (CBDCA + 5-FU) infusion and radiotherapy. STUDY DESIGN: Fifty-eight patients with locally advanced squamous cell head and neck cancer treated with combined chemoradiotherapy between March 1990 and October 1998 were reviewed retrospectively. According to the TNM tumor staging, 6 patients had stage II, 21 stage III and 31 stage IV tumors. The chemotherapy regimen consisted of the combination of 5-FU and CBDCA, for a total of 3 cycles. Both drugs were given as 4-day continuous intravenous infusions during the first and fourth week of radiation therapy: 5-FU at 1000 mg/m2 per day and CBDCA at 75 mg/m2 per day. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 70 Gy. RESULTS: After the completion of chemotherapy and radiotherapy, 34 patients (58.6%) achieved clinical and radiological (computerized tomography and/or magnetic resonance imaging) complete remission, 15 patients (25.9%) partial remission >50%, 5 patients (8.6%) partial remission <50%, and 4 patients (6.8%) had no response. Toxicity was intensive but tolerable. After a median follow-up of 25 months, overall survival and recurrence free survival estimated for the whole patient population was 52% at 3 years, and the median length of recurrence-free survival was 23 months. CONCLUSIONS: Our regimen combining standard single daily fraction radiation with the conventional dose of CBDCA and 5-FU was given without dose modification regardless of the severity of the adverse effects. It gave a clinical complete response at the primary site in 58.6% of patients. With a 52% projected 3-year overall survival, our series compares favorably with similar studies in the literature. Therefore, our results with concomitant CBDCA/5-FU infusion and radiotherapy are encouraging and suggest that CBDCA can be substituted for cisplatin with a good therapeutic index. PMID- 11765181 TI - 3D-conformal radiation therapy in prostate cancer. Technical considerations after 5 years of experience and 334 patients treated at the Istituto Europeo di Oncologia of Milan, Italy. AB - AIMS AND BACKGROUND: To report the technique of 3D-conformal radiation therapy (3D-CRT) currently used at our Institute for the treatment of prostate cancer with a curative intent. A critical review of the technical aspects of the technique is provided. METHODS AND STUDY DESIGN: Between December 1995 and October 2000, 334 patients with biopsy-proven adenocarcinoma of the prostate were treated with 3D-CRT. All patients were treated in a prone position with 15 MV X ray beams and a 6-field technique for all but 20 patients, who were treated with a 3-field technique. Patients were simulated with the rectum and bladder empty. To ensure reproducible positioning, custom-made polyurethane foam or thermoplastic casts were produced for each patient. Subsequently, consecutive CT scan slices were obtained. The clinical target volume and critical organs (rectum and bladder) were identified on each CT slice. The beam's eye view technique was used to spatially display these structures, and the treatment portals were manually shaped based on the images obtained. The beam apertures were initially realized by conventional Cerrobend blocks (48 patients), which were replaced in October 1997 by a computer-driven multi-leaf collimator. The total target dose prescribed at the ICRU point is 76 Gy, delivered in 38 fractions and 54 days. The seminal vesicles are excluded at 70 Gy. Dose-volume histograms were obtained for all patients. If more than 30% of the bladder and/or more than 20% of the rectum receive >95% of the prescribed total dose, the treatment plan is judged as unsatisfactory and is adjusted. The dose-volume histogram can be improved by changing the beam's arrangement and/or weights or by introducing or modifying the wedge filters. CONCLUSIONS: 3D-CRT in prostate cancer patients is a highly sophisticated and time-consuming method of dose delivery. Important technical issues remain to be clarified. PMID- 11765182 TI - Impaired perforin-dependent NK cell cytotoxicity and proliferative activity of peripheral blood T cells is associated with metastatic melanoma. AB - AIMS AND BACKGROUND: Patients with metastatic melanoma often have defects in the percentage and function of peripheral blood NK cells, which are involved in the non-specific innate antitumor immune response, and T cells, which participate in the specific acquired antitumor immune response. The aim of this study was to investigate in more detail not only the percentage but also the activation status and function of NK and T cells in patients with metastatic melanoma prior to therapy. METHODS: The percentage of peripheral blood CD56+ NK cells, CD3+ T cells and their CD4+ and CD8+ subsets, as well as the expression of the activation antigens CD69, CD38 and HLA-DR were analyzed by flow cytometry. The functional capacity of NK cells was evaluated by the 51-chromium release cytotoxicity assay, while the proliferative activity of T cells was estimated by the lymphocyte transformation test to mitogen phytohemagglutinin. RESULTS: The results obtained in this study have revealed a new aspect of NK and T cell dysfunction that is not, as commonly reported, associated with a decrease in their percentage. Moreover, a significant number of the investigated patients had a higher percentage of NK cells that did not lead to improved NK cell cytotoxicity as a result of the detected defect in the NK cell perforin-mediated cytotoxic mechanism of tumor cell lysis. The impaired proliferative response of T cells was associated with a decreased expression of the activation antigen HLA-DR. CONCLUSION: The novel finding in this study of melanoma patients with metastatic disease is the impaired perforin-dependent NK cell cytotoxic mechanism, which was recently shown to be primarily responsible for preventing metastasis. Another interesting finding was the generally hyporeactive status of T cells, possibly resulting from persistent antigenic stimulation. The observed dysfunction of NK and T cells in patients with metastatic melanoma prior to therapy point to the need to supplement chemotherapy with appropriate immunotherapeutic agents in order to overcome the immunosuppression associated with advanced malignancy. PMID- 11765183 TI - Gluteal abscess caused by perforating rectal cancer: case report and review of the literature. AB - An unusual case is described in which an abscess developed remote from a carcinoma of the rectum. A 52-year-old Japanese man developed a gluteal abscess six months after radiation therapy for unresectable carcinoma of the rectum. This case is presented with a review of the literature. Perforating carcinoma of the colon and rectum with abscess formation is best treated by preliminary total diversion colostomy and local drainage of the abscess. However, the mortality rate is still high. PMID- 11765185 TI - Epithelial ovarian cancer in female pseudohermaphroditism. A diagnosis by computed tomography and review of the literature. AB - We describe the case of a patient proven to be a female pseudohermaphrodite with a complete virilization syndrome who developed an epithelial tumor of the ovary of borderline malignancy. The tumor appeared as an abdominal mass with cystic features on ultrasonography. The diagnosis of the intersexual condition and adnexal cancer was made by computed tomography (CT). PMID- 11765184 TI - Brain metastases from colorectal carcinoma. AB - AIMS AND BACKGROUND: Brain metastases are an unusual finding in patients with colorectal carcinoma. We wished to determine the clinical presentation, the time interval between the diagnosis of colorectal carcinoma and the appearance of brain metastases, and the overall survival. PATIENT CHARACTERISTICS: The median age of our patients was 61 years. Brain metastases developed subsequently to the diagnosis of colorectal cancer in nine patients. All patients had neurologic symptoms. All patients had progressing systemic disease at the moment of intracranial presentation. Four patients received whole brain radiation therapy. The median survival was 11 weeks. DISCUSSION: The development of brain metastasis is a late event in the course of colorectal carcinoma and occurs most often in patients with extensive systemic disease that contraindicates surgical resection. Radiotherapy can improve the survival of this group of patients whereas the role of chemotherapy is still unclear due to the low frequency of such cases. PMID- 11765186 TI - Extraordinarily elevated CA19-9 in benign conditions: a case report and review of the literature. AB - Carbohydrate antigen CA19-9 is commonly used in the diagnosis of pancreatic and biliary malignancies. However, increases in its level in benign conditions such as acute cholangitis or pancreatitis have also been reported. A 79-year-old woman presented with cholangitis and a pancreatic pseudocyst while showing elevation of CA19-9 up to 35,500 U/mL. The patient was adequately treated and at two months' follow-up the CA19-9 level had returned to normal. PMID- 11765188 TI - A case report of multicentric Castleman's disease with simultaneous Epstein-Barr virus infection. AB - Castleman's disease is a rare B-cell lymphoproliferative disorder of unknown etiology. In this report we describe a 54-year-old woman with a 10-year history of asymptomatic bilateral, multiple cervical lymph node enlargements. She was not evaluated by lymph node biopsy during this period. She had been well until four months previously. The patient presented with multiple enlarged lymph nodes and systemic symptoms including fever, sweats, weight loss, and anorexia. Two lymph nodes were biopsied, yielding a diagnosis of multicentric Castleman's disease (MCCD) of mixed hyaline-vascular and plasma cell type histology. Serologic studies revealed the simultaneous presence of an acute Epstein-Barr virus (EBV) infection. She experienced an aggressive clinical course with a fatal outcome. PMID- 11765187 TI - Pleuropulmonary blastoma in a child presenting with pneumothorax. AB - Pleuropulmonary blastoma is an uncommon primary malignant tumor of the lung. Surgery is the most important part of the treatment. Despite the use of chemotherapy with or without radiotherapy, the prognosis is poor. Here we report on the case of a 2.5 year-old boy presenting with pneumothorax who turned out to have a right hemithoracic mass. The patient underwent surgical resection of the mass. Pathologic diagnosis was type II pleuropulmonary blastoma. Postoperative thoracic CT showed nodular residual densities so the patient was given adjuvant combination chemotherapy with cisplatin and etoposide. He has been disease free for 12 months. PMID- 11765189 TI - Primary malignant lymphoma of the parotid gland report of three cases. AB - AIMS AND BACKGROUND: To document the clinicopathologic features and treatment modalities of primary malignant parotid gland lymphoma, based on three cases diagnosed and treated at Oldchurch Hospital, Romford, UK. METHODS: Three patients, two with stage II and one with stage IV disease, received primary treatment consisting of chemotherapy following surgical biopsy. RESULTS: All three patients obtained rapid complete remission during their scheduled chemotherapy. One patient is alive without evidence of disease 12 months from the end of treatment. One patient, a frail, elderly gentleman, died due to massive pneumonia while in complete remission for two months. The third patient, who developed local recurrences in both parotid glands without transformation of his low-grade histology, achieved a second complete remission following chemo- and radiotherapy. All side effects were of a mild nature. CONCLUSION: Malignant lymphoma of the parotid gland is a chemo- and radiosensitive disease. PMID- 11765190 TI - Gastrointestinal autonomic nerve tumor: case report and review of the literature. AB - Gastrointestinal autonomic nerve (GAN) tumor is an uncommon specialized form of gastrointestinal stromal tumor (GIST). We report the case of a 46-year-old man affected by this tumor. The neoplasm arose from the sigmoid colon. The patient underwent surgery but eight months later an omental relapse occurred. A second laparotomy was successfully performed and the patient is free of disease at 21 months of follow-up. To our knowledge this is the first case of a large bowel GAN tumor described in the literature. PMID- 11765191 TI - Combined surgical-medical treatment of genital warts in HIV positive patients. PMID- 11765192 TI - Ablative techniques in the treatment of cervical lesions. PMID- 11765193 TI - Treatment of cervical intraepitelial neoplasia using the loop electrosurgical excision procedure. PMID- 11765194 TI - Cervical loop excision: colposcopy limits in pre-surgical assessment of CIN lesions. PMID- 11765195 TI - Histologic classification of endometrial lesions. PMID- 11765196 TI - Transvaginal ultrasound in the diagnosis of endometrial abnormalities. PMID- 11765197 TI - Indications and procedure for operative hysteroscopy in oncology. PMID- 11765198 TI - Image digitalization and processing: the role of informatics in colposcopy. PMID- 11765200 TI - Endometrial effects of pure antiestrogens. PMID- 11765199 TI - Raloxifene and endometrial cancer. PMID- 11765201 TI - Hormone replacement therapy and risk of endometrial cancer. PMID- 11765202 TI - Surgical treatment of invasive cervical cancer. PMID- 11765203 TI - Neo-adjuvant medical treatment for advanced cervical cancer. PMID- 11765204 TI - Medical treatment of endometrial cancer. PMID- 11765205 TI - Integrated therapies for locally advanced cervical carcinoma. PMID- 11765206 TI - Radiotherapy for the management of cervical and endometrial cancer. PMID- 11765207 TI - Incidence, mortality, and survival for tumors of the female genital tract: the Romagna Cancer Registry data. PMID- 11765208 TI - Cervical carcinoma screening in Italy: current situation and future plans. PMID- 11765209 TI - Current significance of additional tests to cytology. PMID- 11765210 TI - Computer assisted cytology. PMID- 11765211 TI - Quality control of colposcopy. PMID- 11765213 TI - Time for 'digital signaling'? PMID- 11765212 TI - Cervical cancer in HIV. PMID- 11765214 TI - Drug transporters and their role in multidrug resistance of neoplastic cells. AB - Multidrug resistance (MDR) of neoplastic cells, i.e. resistance towards large groups of unrelated drugs, represents the phenomenon that dramatically depresses the effectiveness of cancer chemotherapy. Membrane transport of ATPases from ABC superfamily plays an important role in MDR. In the present paper we are aiming to compare two members of this family: P-glycoprotein (PGP products of mdr genes) and multidrug resistance-associated protein (MRP, products of mrp genes) and their impact for MDR of neoplastic cells. PMID- 11765215 TI - Functional properties of the epithelial Ca2+ channel, ECaC. AB - ECaC is the first member of a new subfamily of Ca2+ channels embedded in the large TRPC family that includes numerous channel proteins. The channel has been proposed as the main gatekeeper of transcellular Ca2+ transport in kidney and intestine. The functional characterization of this channel is evolving rapidly and may have far reaching consequences for other channels of the TRPC family. The goal of this mini-review is to summarize the major functional and structural characteristics of ECaC, including (i) its proposed functional role, (ii) its channel structure and expression pattern, (iii) its main electrophysiological characteristics and (iv) its regulation. PMID- 11765216 TI - Salinity dependent Na+-K+ATPase activity in gills of the euryhaline crab Chasmagnathus granulata. AB - The occurrence and response of Na+-K+ATPase specific activity to environmental salinity changes were studied in gill extracts of all of the gills of the euryhaline crab Chasmagnathus granulata from Mar Chiquita coastal lagoon (Buenos Aires Province, Argentina). All of the gills exhibited a salinity dependent Na+ K+ATPase activity, although the pattern of response to environmental salinity was different among gills. As described in other euryhaline crabs highest Na+ K+ATPase specific activity was found in posterior gills (6 to 8), which, with exception of gill 6, increased upon acclimation to reduced salinity. However, a high increase of activity also occurred in anterior gills (1 to 5) in diluted media. Furthermore, both short and long term differential changes of Na+-K+ATPase activity occurred among the gills after the transfer of crabs to reduced salinity. The fact that variations of Na+-K+ATPase activity in the gills were concomitant with the transition from osmoconformity to ionoregulation suggests that this enzyme is a component of the branchial ionoregulatory mechanisms at the biochemical level in this crab. PMID- 11765217 TI - Evidence for activation of carcinogenic o-anisidine by prostaglandin H synthase: 32P-postlabelling analysis of DNA adduct formation. AB - 2-Methoxyaniline (o-anisidine) is a urinary bladder carcinogen in both mice and rats. Since the urinary bladder contains substantial peroxidase activity, we examined the ability of prostaglandin H synthase (PHS), a prominent enzyme in the urinary bladder, to activate this carcinogen to metabolites binding to macromolecules. Using [14C]-labeled o-anisidine, we observed substantial PHS dependent binding of o-anisidine to protein, DNA and polydeoxyribonucleotides [poly(dX)]. This binding is inhibited by radical scavengers glutathione, ascorbate and NADH. The nuclease P1 and 1-butanol extraction enrichment procedure of the 32P-postlabeling analysis of DNA modified by activated o-anisidine provide evidence that covalent binding to DNA is the principal type of DNA modification. Deoxyguanosine is determined to be the major target for binding of o-anisidine in DNA. The possibility that o-anisidine is carcinogenic to the rodent urinary bladder via its activation by bladder PHS is suggested. The results presented here are the first report demonstrating a PHS-mediated activation of o-anisidine to reactive species forming covalent DNA adducts. PMID- 11765218 TI - Background osmolyte current involved in cell volume regulation of neuroblastoma x glioma hybrid NG108-15 cells. AB - Recently, we showed that at constant extracellular osmolarity, the volume of NG108-15 cells was dependent on the external NaCl concentration and we assumed that the responsible mechanism was mediated by background channels (Rouzaire Dubois et al. 1999). In order to confirm this view, the mean cell volume and the background current of NG108-15 cells were measured under different experimental conditions, after blockade of specific volume regulating mechanisms and ion channels. When the external NaCl concentration was decreased, the reversal potential of the background current was shifted toward negative values and the membrane conductance decreased. Opposite effects were observed when the NaCl concentration was increased. Substitution of external Na+ with various monovalent cations altered the mean cell volume by: Rb+, +17%; Cs+, +15%; K+, +10%; Li+, 6%; choline, -9%; N-methylglucamine, -25% . The reversal potential of the background current and the membrane conductance were altered by these Na+ substitutes in such a way that the cell volume increased linearly with the background current at -60 mV. Substitution of external Cl- with various monovalent anions altered the mean cell volume by: I-, +4%; Br-, 0%; NO-, -3%; F , -5%; isethionate, -30%; gluconate, -50%. Cl- substitutes did not significantly alter the background current at -60 mV, except F- which increased it by 39%. These results suggest that 1. the cell volume is dependent on ion fluxes through background channels; 2. electrogenic cation fluxes are larger than anionic ones and the background current is proportional to the difference between these fluxes; 3. whereas external cations do not interfere with anion fluxes, external anions alter cation fluxes. PMID- 11765219 TI - Mammary gland carcinoma-related increase of type I iodothyronine 5'-deiodinase activity in Sprague-Dawley rats. AB - Type I, iodothyronine 5'-deiodinase (5'-DI) catalyses deiodination of the prohormone thyroxine (T4) to the metabolically active 3,5,3'-triiodo-L-thyronine (T3). The present study was undertaken to investigate the activity of 5'-DI in rat mammary gland tumours representing various combinations of histologically defined papillary, cribriform or comedo patterns of ductal carcinomas. Female Sprague-Dawley rats were given two doses 50 mg x kg(-1) 1-methyl-1-nitrosourea (MNU) in abdominal parts on the 52nd day and 113th day of age. We have found that in comparison with non-lactating mammary gland, the activity of 5'-DI in all mammary gland tumours studied was significantly (p < 0.0001) increased and that the 5'-DI activity, expressed as pmol of 125I- released per min and per mg of protein, in malignant mammary gland tumours was found to be at least two order higher than that of intact mammary non-lactating gland. From our data, we suggest that thyroid hormone in mammary gland tumours might play a significant role to support high energetic expenditure of neoplastic tissues. PMID- 11765220 TI - Delayed fluorescence induction transients: mathematical modelling based on the chosen kinetic models. AB - The paper deals with mathematical modelling of the transients obtained by fitting of delayed fluorescence (DF) induction trace. The transients are in certain, doubtless connection with electrochemical gradient (ECG) formed across thylakoid membranes upon illumination. The fitting of the C and D transients by using consecutive model for first-order reactions (A --> B --> C) showed that they might play a role of the intermediate (B), according to scheme down bellow: ("A1 state")ECG (k1(C transient))--> C transient (k2(C transient))--> products, ("A2 state")ECG (k1(D transient))--> D transient (k2(D transient))--> products. The two ECG controlled "states" (A1 & A2) are not the same, which does not exclude some sort of proportionality. On the other hand, the E band, contributing mainly to the stationary level of DF induction trace, may be fitted by parallel model of at least two first-order reactions. PMID- 11765221 TI - Lead-induced changes of cation-osmotic hemolysis in rats. AB - Erythrocyte microrheology changes were measured using cation-osmotic hemolysis (COH) in healthy rats and rats after 6 and 12 months of lead ingestion. Using COH, properties of two membrane constituents, spectrine membrane skeleton and membrane bilayer were studied. COH in rats after 12 months of lead ingestion was significantly lower only in the area with lower ionic strength (15.4-61.6 mmol x l(-1) of NaCl) (p < 0.01 resp. p < 0.05). No changes in COH were found after 6 months of continuous lead ingestion. The relation between cation-osmotic hemolysis and erythrocyte deformability is being discussed. PMID- 11765222 TI - HLA-DRB1 antigens in Taiwanese patients with juvenile-onset systemic lupus erythematosus. AB - OBJECTIVE: This study was done to investigate the frequency of HLA-DRB1 antigens in juvenile-onset systemic lupus erythematosus (SLE) in the Taiwanese population. PATIENTS AND METHODS: Thirty-four Taiwanese patients with juvenile onset SLE and 200 unrelated healthy controls were studied. HLA-DRB1 typing was performed with polymerase chain reaction (PCR) and the sequence-specific oligonucleotide probe (SSO) typing method. RESULT: Among the 14 investigated DRB1 alleles, the frequency of HLA-DRB1*1602 was higher in juvenile onset SLE patients than the controls (15.15% vs 4.50%, odds ratio 3.66, 95% confidence interval 1.15-11.68, Pc = 0.04). Although there were differences in the frequencies of DRB1*0301, DRB1*0803, and DRB1*1501 between patients and controls, the associations were statistically insignificant. CONCLUSION: The frequency of HLA-DRB1*1602 was significantly higher in patients with juvenile onset SLE than in healthy controls. This finding differs from those in the previous studies in Caucasian and Japanese adult onset SLE patients. PMID- 11765223 TI - Lung cancer associated with several connective tissue diseases: with a review of literature. AB - The association between connective tissue disease (CTD) and malignancy has been an area of debate. Whether this relation is casual or causal, it would seem that the importance of their possible relationship is twofold. The purpose of this study is to describe the clinical features of lung cancer associated with several CTDs. Patients with CTD associated with lung cancer were retrospectively evaluated. A review of the clinical features of 153 reported cases from 1944 to the present was conducted. There were 82 females and 71 males, with a median age of 58. Histological types of lung cancer were as follows, bronchioloalveolar cell carcinoma (39 cases), adenocarcinoma (36), squamous cell carcinoma (28), small cell lung cancer (27), large cell carcinoma (6), others (8), and unknown (10). There was a relationship between smoking and development of lung cancer in patients with rheumatoid arthritis (RA) and polymyositis/dermatomyositis (PM/DM). The majority of patients with progressive systemic sclerosis (PSS) who developed lung cancer were female, with underlying interstitial fibrosis, and most tumors were of bronchioloalveolar cell or adenocarcinoma cell type. Patient characteristics were significantly different among the various groups of CTD associated with lung cancer. PMID- 11765224 TI - Expression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP) in human articular chondrocytes: possible contribution to the resistance to Fas-mediated death of in vitro cultured human articular chondrocytes. AB - Although chondrocyte apoptosis has been noted in arthritic joints, the mechanism is not clear. To investigate whether Fas-mediated apoptosis has a role in this process, the presence of Fas mRNA and expression of cell surface Fas protein in monolayer-cultured human articular chondrocytes was analyzed. Fas mRNA was found in all chondrocyte samples analyzed; moreover, the majority of cells in chondrocyte populations expressed cell-surface Fas (12-90%, average 49%). Nevertheless, treatment with an agonistic anti-Fas antibody did not induce significant apoptosis in these chondrocytes in vitro. However, it was also found that chondrocytes express Fas-associated death domain-like interleukin-1beta converting enzyme-inhibitory protein (FLIP), a molecule which blocks Fas-mediated apoptosis. Correspondingly, activation of caspase-8 was minimal in these cultured chondrocytes. In conclusion, although human articular chondrocytes do express cell-surface Fas, this receptor did not fully mediate death-inducing signals in vitro. This resistance to Fas may be partly due to the constitutive expression of FLIP. PMID- 11765225 TI - Elevation of soluble interleukin-2 receptor levels in the bronchoalveolar lavage from patients with systemic sclerosis. AB - This study was designed to investigate the levels of IL-2 and its soluble receptor (sIL-2R) in bronchoalveolar lavage fluid (BALF) from patients with systemic sclerosis (SSc). We studied 18 patients with SSc and 10 healthy volunteers. Based on high-resolution computed tomography lung scans the patients were divided into two groups, those with (SSc-ILD group, n= 10) and those without (SSc group, n = 8) evidence of interstitial lung disease (ILD). Both groups showed significantly higher total cell and neutrophil counts in the BALF than controls. The SSc group also showed significantly higher levels of lymphocytes than controls. IL-2 was not detectable in BALF. The patients showed significantly higher levels of sIL-2R than controls (77.8% vs 20%, P=0.005). The median sIL-2R levels detected did not differ between the two patient groups (SSc-ILD 270 pg/ml, SSc 232 pg/ml). This study suggests that SSc patients with or without ILD have elevated levels of sIL-2R in BALF and that in some of these patients this finding could be explained by subclinical pulmonary inflammation. PMID- 11765226 TI - Predictors of bone mineral density in healthy males. AB - Osteoporosis (OP) is a growing health problem not only in women but also in men. It is well known that men lose bone during aging and are at risk for OP, but the risk factors for OP in men remain controversial. To assess determinants of bone mineral density (BMD) in the spine and femoral neck, 37 healthy men aged 43-73 years were measured using dual photon absorptiometry. Predictors of lumbar spine and femoral neck BMD were determined using multiple linear regression analysis. Backward elimination procedure was used to identify variables significantly related to BMD. The independent variables entered the regression model included age; body mass index (BMI); smoking history; alcohol intake; urinary calcium and hydroxyproline; and serum concentrations of osteocalcin, parathyroid hormone, testosterone, growth hormone, and cortisol. Backward regression analysis indicated that testosterone, cortisol, and BMI were significant predictors of BMD in the lumbar spine while testosterone, hydroxyproline, and osteocalcin were significant predictors of BMD in the femoral neck. Testosterone, cortisol, and BMI accounted for 44% of the total variance in lumbar spine BMD, and testosterone, hydroxyproline, and osteocalcin accounted for 20% of the total variance in femoral neck BMD. These observations suggest that testosterone, cortisol and BMI are determinants of lumbar spine BMD, while testosterone, urinary hydroxyproline, and osteocalcin are determinants of femoral BMD in healthy men. PMID- 11765227 TI - Lymphocyte subsets in lung tissues of interstitial pneumonia associated with untreated polymyositis/dermatomyositis. AB - This study was designed to evaluate the distribution of lymphocyte subsets in lung specimens obtained by surgical lung biopsy from 12 patients with interstitial pneumonia associated with untreated polymyositis/dermatomyositis (PM/DM). Differences of histological findings and distributions of lymphocyte subsets between PM and DM were also evaluated. Distributions of B lymphocytes, CD4-positive T lymphocytes, and CD8-positive T lymphocytes were evaluated immunohistochemically. Interstitial pneumonia was pathologically classified as basically nonspecific interstitial pneumonia (NSIP) in all patients. Immunohistochemically, the distribution of B lymphocytes was mostly restricted to inside and/or around lymphoid follicles. The CD4-positive T lymphocytes were distributed diffusely in fibrotic areas and unrelated to lymphoid follicles. Most CD8-positive T lymphocytes were diffusely distributed, especially in relatively normal alveoli. There were no significant differences in the distribution of lymphocyte subsets between PM and DM. Although the distribution of B lymphocytes and CD4- and CD8-positive T lymphocytes in the lung were different, there were no significant differences in distributions of lymphocyte subsets between PM and DM. PMID- 11765228 TI - Radiographic osteoarthritis of the hip joint in Turkey. AB - The prevalence of hip osteoarthritis (OA) varies greatly across different geographic areas. Limited data exist about the prevalence of radiographic hip OA in the Turkish population. The aim of this study was to estimate the prevalence of radiographic hip OA in Turkey utilizing a random sample. That sample consisted of radiographs filed at the Department of Urology, Gazi University Hospital, Ankara, and included patients aged 25 years and older (range 25-97 years). Plain supine abdominal radiographs and intravenous pyelographies were evaluated using the Kellgren and Lawrence (K&L) grading system. Evaluations were made of 1,248 hips in 682 patients (205 women and 477 men). Overall, 8.8% of the hips evaluated had radiographic hip OA (K&L grade 2 or higher). Both hips were visible in 566 patients. Of those patients 11.7% had radiographic hip OA in either one or both hips (9.4% of women and 12.6% of men), and 51.5% of whom had bilateral findings. Prevalence increased with age and was 1.9%, 16.1%, and 21.5% for age ranges 25 39, 40-54, and 55 years and older, respectively. Patients aged 40 years and older had significantly more radiographic hip OA than those younger than 40 years (P<0.001). Men had a higher frequency than women after the age of 40 years, but this did not reach statistical significance. In most patients radiographic findings indicated only mild disease. Three patients had grade 3 disease and only one patient (aged 68 years) had grade 4 disease. Among patients aged 40 years or older. 1.1% had grade 3 or 4 disease. These findings suggest that K&L grade 2 OA changes emphasizing osteophytes at hip joints are not uncommon in the Turkish population, especially among those aged 40 years and older. However, frequency of moderate or severe radiographic hip OA may be low. PMID- 11765229 TI - Bone mineral density, biochemical markers of bone turnover, and hormonal status in men with systemic lupus erythematosus. AB - The aim of this study was to evaluate bone mineral density (BMD), biochemical markers of bone turnover, and hormone levels in men with systemic lupus erythematosus (SLE). BMD at L2-L4 lumbar vertebrae (LS), left proximal femur neck, and radius at the ultradistal and mid-33% region was measured by dual energy X-ray absorptiometry in 23 men with SLE (mean age, disease duration, and cumulative corticosteroid dose were 45.6 years, 11.9 years, and 33.410 g, respectively) and 40 healthy, age- and sex-matched controls. Biochemical markers of bone turnover, parathyroid hormone and 25-hydroxyvitamin D (25-OH-D), testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels were measured. There was no difference in BMD between the SLE and control group. The prevalence of osteoporosis was 17.4% (4 out of 23), found at LS. Biochemical markers of bone turnover were within the reference range. There was a high prevalence of hypovitaminosis D (65.2%), hypotestosteronism (62.5%), and hypodehydroepiandrosterone sulfate (100%). There was no correlation between BMD and duration of disease, corticosteroid doses, SLE Disease Activity Index (SLEDAI), SLE Collaboration Clinics/American College of Rheumatology (SLICC/ARC) damage index, or markers of bone turnover. Bone-specific alkaline phosphatase (BSAP) (r, -0.500; P=0.018) and DHEAS (r, -0.511; P=0.013) correlated with the daily corticosteroid dose. Despite corticosteroid therapy, bone mass in men with SLE was not decreased. PMID- 11765230 TI - Assessment of the husbandry problems of reptiles on the basis of pathophysiological findings: a review. AB - Many health problems in animals are related to management and feeding. A large number of husbandry problems in reptiles lead to pathophysiological situations. Assessment of the husbandry problems of reptiles involves detective work that can only be achieved as a result of close cooperation and exchange of information between the owner and the pathologist. Reptiles, being ectothermic, depend for their physiological functioning largely on the quality of their surroundings. There are a large number of factors which influence the normal functioning of a reptile both in nature and in captivity. These factors can be described in terms of primary and secondary factors. Primary factors are the construction of terraria, light, heat, food, and water, and grouping of animals. Secondary factors are daylight regimen, arrangement of heating elements, type and composition of food, quality of water, and freedom from stress. Also important are ventilation, humidity, sites for resting and/or hiding, structure of the floor and of rocks, and branches for climbing activities. Hygiene is also an important aspect because poor hygiene often is directly related to problems. All these factors are dealt with in this review. PMID- 11765231 TI - Chronic hepatitis in the dog--a review. AB - Chronic hepatitis is a heterogeneous group of inflammatory-necrotizing diseases of the liver. There is controversy in both human and veterinary medicine about the classification of chronic hepatitis and this is likely to remain until a classification based on aetiology rather than on morphology is introduced. Controversy exists as to whether chronic hepatitis in dogs is comparable to the human disorder. The aetiology of chronic hepatitis in dogs is poorly understood, whereas in humans an increasing number of viral causes have been found. Liver biopsy is essential for the diagnosis of chronic hepatitis both in dogs and in humans. Histopathological evaluation of the liver is required to make the diagnosis, which is based on the presence of liver cell necrosis and inflammatory reaction. The proposed criteria for the classification of hepatitis in dogs are then as follows: aetiology is the primary denominator (infectious, drug induced, autoimmune, or, if unknown, idiopathic). The other criteria are histopathological, with severity reflecting the severity of the necro inflammatory activity (minimal, mild, moderate or severe) and chronicity reflecting the extent of fibrosis (none, mild, moderate, severe or cirrhosis). PMID- 11765233 TI - Developments in veterinary herd health programmes on dairy farms: a review. AB - This review article addresses some major developments in herd health programmes for dairy farms over the last decades. It focuses particularly on herd health and production management programmes that use protocols and monitoring activities. The article further emphasizes the need for merging herd health programmes with quantitative epidemiological principles and methods. Subsequently, this article points to the latest developments regarding quality assurance in the dairy sector and some quality management methods. Quality should be regarded in its broadest sense. The importance of integrating veterinary herd health programmes and quality (risk) management support at a dairy farm level is stressed. Examples are provided. PMID- 11765232 TI - How does Mycobacterium avium subsp. paratuberculosis resist intracellular degradation? AB - Paratuberculosis is a chronic, progressive disease of mainly ruminants caused by the facultative intracellular bacterium, Mycobacterium avium subsp. paratuberculosis. Infection usually occurs in young animals through oral uptake of food contaminated with the organisms. The ingested bacteria are transcytosed through M-cells overlying the Peyer's patches and are released in the stroma, where they are taken up by macrophages. Inside the macrophage, the mycobacteria resist enzymatic and toxic degradation and multiply until the infected macrophage ruptures. The thick, lipid-rich cell envelope is mainly responsible for micobacterial resistance. In addition to its barrier effect, which provides protections, the mycobacterial cell wall also contains several biologically active components that down-regulate the bactericidal function of macrophages. The basic survival strategy of pathogenic mycobacteria can be viewed at three levels: selective use of relatively safe entry pathways that do not trigger oxidative attack, modification of the intracellular trafficking of mycobacteria containing phagosomes, and modulation of the cooperation between the innate and specific immunity. In doing so, pathogenic mycobacteria are successful intracellular organisms that survive and multiply inside macrophages. Current understanding about the survival strategies of M. a. paratuberculosis and its implications in the epidemiology, diagnosis, and control of the disease are discussed. PMID- 11765234 TI - Culture of bovine bone marrow progenitor cells in vitro. AB - In vitro methylcellulose cultures of bovine bone marrow progenitor cells were developed. An existing technique described for bovine species was compared to a method for human tissue and further adapted during subsequent experiments. Bovine bone marrow samples were collected at the slaughterhouse, and mononuclear cells were separated by gradient centrifugation (1.077 g/ml specific density and 400 g). The use of 3% bovine leucocyte-conditioned medium, produced by stimulation of blood lymphocytes with 4 microg/ml concanavalin A and harvested on day 4 of culture, gave better results than the use of supernatant of the human bladder carcinoma 5637, which is widely used in human bone marrow cultures. However, bovine leucocyte-conditioned medium was not added to erythroid cultures because inhibitory effects were observed. Erythroid colonies were stimulated with erythropoietin, and hemin was added to enable microscopic identification. Reduced oxygen tension was necessary to induce growth of erythroid colonies. This was not necessary for myeloid cultures. In conclusion, the results of this study show that the growth of myeloid and erythroid colonies in methylcellulose-based medium requires different culture conditions, which are different from the culture conditions for human cells. PMID- 11765235 TI - Salmonella (sero)types and their resistance patterns in pig faecal and post mortem samples. AB - The purpose of this survey was to take stock of porcine Salmonella isolates derived from faecal and post-mortem samples over a 4-year period. Salmonella was isolated by direct inoculation on BGA(NO)-plates (faeces, intestinal content) or sheep blood agar (organs). Antimicrobial susceptibility was tested by the agar diffusion method. Salmonella was isolated in 4.2% of all porcine submissions received at the Animal Health Service. A total of 1305 salmonellae were isolated from a total of 1279 submissions from 1008 different herds. Salmonella Typhimurium was the most frequently isolated serotype (88%), and Salmonella Typhimurium DT104 was the most frequently isolated phagetype (17.2% of Salmonella Typhimurium). Resistance to antimicrobials occurred in 47.3% of all isolates, mainly those of the multiresistant phagetype DT104. Other pathogens were isolated in more than 50% of the submissions. In cases of clinical diarrhoea, multiple pathogens may be involved and therapy and preventive measures should be adjusted accordingly. PMID- 11765237 TI - The efficacy of a new single post-exposure treatment of rabies in mice without vaccination. AB - Local application of rabies immune serum and isoprinosine, an immunomodulator with antiviral activity was effective in mice infected with a sylvatic rabies virus. In this way, a single medical or veterinary treatment is only required, which is particularly important for developing but also for developed countries. The importance of using a post-exposure potency test to monitor rabies vaccines is emphasized. The same principle could be applied to other emerging viral infections of humans (for example, human immunodeficiency virus infection) and animals, for which no effective vaccines are available at this moment. PMID- 11765236 TI - Cardiopulmonary effects of three different anaesthesia protocols in cats. AB - To develop an alternative anaesthetic regimen for cats with cardiomyopathy, the cardiopulmonary effects of three different premedication-induction protocols, followed by one hour maintenance with isoflurane in oxygen: air were evaluated in six cats. Group I: acepromazine (10 microg/kg) + buprenorphine (10 microg/kg) IM, etomidate (1-2 mg/kg) IV induction. Group II: midazolam (1 mg/kg) + ketamine (10 mg/kg) IM induction. Group III: medetomidine (1.5 mg/m2 body surface) IM, propofol (1-2 mg/kg) IV induction. Heart rate, arterial blood pressure, arterial blood gases, respiration rate, and temperature were recorded for the duration of the experiment. In group I the sedative effect after premedication was limited. In the other groups the level of sedation was sufficient. In all groups premedication resulted in a reduced blood pressure which decreased further immediately following induction. The reduction in mean arterial pressure (MAP) reached statistical significance in group I (142+/-22 to 81+/-14 mmHg) and group II (153+/-28 to 98+/-20 mmHg) but not in group III (165+/-24 to 134+/-29 mmHg). Despite the decrease in blood pressure, MAP was judged to have remained within an acceptable range in all groups. During maintenance of anaesthesia, heart rate decreased significantly in group III (from 165+/-24 to 125+/-10 b.p.m. at t=80 min). During anaesthesia the PCO2 and PO2 values increased significantly in all groups. On the basis of the results, the combination acepromazine-buprenorphine is preferred because heart rate, MAP, and respiration are acceptable, it has a limited sedative effect but recovery is smooth. PMID- 11765238 TI - Effects of 'navicular' shoeing on equine distal forelimb kinematics on different track surface. AB - Orthopaedic shoeing applied for disorders such as navicular disease is mostly evaluated on hard track surfaces, but very often horses are ridden only on soft tracks. To compare the effects of normal shoes, eggbar shoes, and shoes with heel wedges (5 degrees) on the kinematics of the distal forelimb on hard and soft track surfaces, eleven sound Dutch Warmblood horses were led across three different tracks (an asphalt, a fibre/sand mix (= Agterberg), and a pure sand track) with three different shoe types (a normal shoe, an eggbar shoe, and a shoe with heel wedges). The hoof rotation and the maximal extension of the fetlock joint at midstance period were recorded by an infrared-light based gait analysis system (ProReflex) at walk and at trot. Statistical analysis revealed significant effects of track and shoe type, and a shoe-track interaction (p<0.05). On soft track surfaces, the equilibrium of the distal forelimb dictated a 1.5-4 degrees forward rotation of the normal or eggbar shod foot, the most on a sand track. The wedge effect on hoof rotation, however, was always significantly greater, but similar to that on the hard track surface (5 degrees forward rotation). The maximal fetlock extension was less on a soft surface, in particular on the sand track (p<0.05). This decrease was most pronounced when the horses were shod with heel wedges and was least pronounced with normal shoes. In conclusion, in particular the sand track allows a forward rotation of the hoof and thus relief of pressure in the navicular area, and a decrease in maximal fetlock extension and thus unloading of the fetlock joint. The extra forward rotation of the hoof induced by heel wedges on hard tracks was almost the same on soft track surfaces. Eggbars and fibre/sand mix tracks have intermediate effects on unloading of the distal forelimb. PMID- 11765239 TI - An approach to assessment of the efficiency of dietary energy utilization by horses and ponies kept at riding schools. AB - The ratio of calculated net energy intake (NEi) to calculate net energy requirement (NEr) might serve as an indicator of the efficiency of dietary energy utilization. The ratio was determined for 93 horses and ponies from 10 riding schools. For each animal with an assumed constant body weight, energy intake and energy requirements were assessed. On average, the estimated NEi was 14% greater than NEr. There was a significant, negative association between crude fibre intake and the NEi: NEr ratio. Earlier work indicated that extra fat intake may lead to over estimation of the calculated energy value of the ration due to changes in macronutrient digestibility. Dietary fat concentration was found to range from 32 to 52 g/kg dry matter (5 to 6 g/MJ net energy), but on the basis of digestibility trials this range in fat concentration is too small to significantly influence the NEi: NEr ratio. This study shows that assessment of the efficiency of dietary energy utilization under normal conditions, on the basis of the NEi: NEr ratio is fraught with uncertainty. PMID- 11765240 TI - Salmonella typhimurium DT104 septicaemia with meningitis in neonatal piglets. AB - Clinical salmonellosis in pigs in the Netherlands usually manifests itself as diarrhoea. In finishing pigs this is sometimes accompanied by peracute mortality, mainly in the last month of the finishing period. This is the first report describing Salmonella Typhimurium DT104 infection of 1-week-old suckling piglets in the Netherlands. The piglets showed nervous symptoms and died. The clinical symptoms, gross pathology, histopathological, bacteriological and phagetyping results are presented as well as the antimicrobial resistance pattern. This case is not only important as an extension of the clinical syndrome of salmonellosis in pigs in the Netherlands, but also because of the risk of human infection after consumption of pork or pork products contaminated with this pathogenic and multiple resistant Salmonella clone. PMID- 11765241 TI - A preliminary report on a fat-free diet formula for nasogastric enteral administration as treatment for hyperlipaemia in ponies. AB - A fat-free liquid diet was formulated to be administered by nasogastric tube as therapy for hyperlipaemia in ponies. The liquid diet provided energy, protein, minerals, trace elements, and vitamins in accordance with the requirements of ponies. As sole source of nutrition, the liquid diet fully counteracted fasting induced hyperlipaemia in two healthy ponies. The liquid diet was also used in hyperlipaemic patients, but only in combination with conventional therapy, consisting of intravenous administration of glucose, insulin, and heparin. Although no patients were treated with the liquid diet alone, the liquid diet has potential in the treatment of hyperlipaemia - it is easy to prepare and to administer by nasogastric tube and it provides energy and nutrients to counteract the negative energy balance and low nutritional status of patients. Experience is needed with hyperlipaemic patients that are treated with the liquid diet only. PMID- 11765242 TI - Subclinical rumen acidosis as a cause of reduced appetite in newly calved dairy cows in Denmark: results of a poll among Danish dairy practitioners. AB - A questionnaire survey was conducted among Danish dairy practitioners to investigate reduced appetite and its relation to subclinical rumen acidosis in post partum dairy cows. The 115 practitioners who responded provided service to 325,300 cows representing 46% of the national herd. Results are presented and discussed in relation to the practitioners beliefs regarding occurrence and value of the diagnostic methods used and treatments applied. The most common diagnoses believed to occur were ketosis (26%), rumen acidosis (22%) abomasal disorders (16%), subclinical hypocalcaemia (15%) and milk fever (15%). Subclinical rumen acidosis was considered to be a commonly occurring underlying condition with significant importance as a cause of reduced appetite. Inadequate feeding strategies were considered to be a main cause of subclinical rumen acidosis. However, the veterinary practitioners were apparently reluctant to imply checking of feeding mangement in their diagnostic work. Possibel reasons for this are discussed. According to the national dairy health recording system subclinical rumen acidosis was rarely reported as a diagnosis among attended cases. Apparently, signs and manifestations of the condition were unclear to the practitioners. It is proposed that the discrepancy is partly due to a lack of precise diagnostic tools available to veterinary practitioners at present and partly due to a missing examination of farm specific feeding management. PMID- 11765243 TI - Duration of immunity induced by an adjuvanted and inactivated equine influenza, tetanus and equine herpesvirus 1 and 4 combination vaccine. AB - An adjuvanted vaccine containing inactivated equine influenza, herpesvirus antigens, and tetanus toxoid was administered to young seronegative foals of 8 months of age by deep intramuscular injection in the neck (Group A). The first two vaccinations were given 4 weeks apart. The third was administered 6 months later. Another group of foals (Group B) was vaccinated according to the same scheme at the same time with monovalent equine herpes virus (EHV) vaccine (EHV1.4) vaccine. Antibody responses to the equine influenza (single radial haemolysis; SRH) and tetanus (ToBi ELISA) components of the vaccines were examined from first vaccination until 1 year after the third vaccination. The influenza components of the combination vaccine induced high antibody titres at two weeks after the second vaccination whereafter titres declined until the time of the third vaccination. After the third vaccination, the titres rose rapidly again to remain high for at least 1 year. Antibody titres against tetanus peaked only after the third vaccination but remained high enough to offer protective immunity for at least 1 year. Foals vaccinated with monovalent EHV1.4 remained seronegative for influenza and tetanus throughout the study. Four and a half months after the third vaccination of groups A and B, a third group of animals was vaccinated twice with monovalent EHV1.4 vaccine 4 weeks apart (Group C). Two weeks after the administration of the second dose in the later group, all groups (A, B, C and an unvaccinated control group D) were challenged with EHV-4. Vaccinated foals (Group A, B, C) showed a clear reduction of clinical symptoms and virus excretion after EHV-4 challenge compared with the unvaccinated control foals. No difference could be demonstrated among the vaccinated groups, suggesting that the combination vaccine protects as well as the monovalent vaccine. In EHV1.4-vaccinated foals both antigenic fractions induced clear protection up to 6 months after vaccination (9). It can therefore be anticipated that the efficacy of the combination vaccine against EHV-1 challenge is similar to the efficacy against EHV-1 induced by EHV1.4 vaccination. PMID- 11765244 TI - Commercial diet induced hypothyroidism due to high iodine. A histological and radiological analysis. AB - A number of puppies of the School Hospital of the Faculty of Veterinary Science UBA showed bone changes. Measurement of the iodine content of the commercial diet showed a significant increase in its content. Iodine excess causes alterations in thyroid function and morphology, and its hormones have a direct action on bone formation. Three groups of puppies were fed on different diets: a home-prepared diet, a commercial diet (containing 5.6 mg potassium iodide/kg dry food), and a home-prepared diet supplemented with 5.6 mg potassium iodide/kg dry food. Groups B and C developed hypothyroidism. A significant decrease (p<0.05) in the styloid apophyseal surface was found in groups B and C vs. A, determined by radiography. Histologically, the hypertrophied cartilage was shorter in groups B and C than in group A (p<0.0001). The present results suggest that commercial diets with a high iodine content may cause hypothyroidism and changes in bone metabolism. PMID- 11765245 TI - Health science students with blood-borne pathogen diseases. PMID- 11765246 TI - An introduction to the Lexington report on blood-borne pathogen disease in health science students. PMID- 11765247 TI - Blood-borne pathogen disease in health science students: recommendations from the Lexington conference, November 6-7, 2000. Members of the Student Health Services at Academic Medical Centers Task Force. AB - The Student Health Services at Academic Medical Centers group has been aware since its inception in 1997 of the need for standards for health science schools in dealing with the issue of the student infected with a blood-borne pathogen. In view of the absence of such standards, the group organized a small task force of individuals from several student health services at academic medical centers and from key public and private organizations to develop recommendations for institutional responses to the health science student infected with a blood-borne pathogen. This article reviews the current status of relevant position statements of state medical boards, certain professional organizations, and other English speaking countries, and reviews current literature. A discussion of ethical considerations of the task force's recommendations precedes the specific recommendations, which are divided into four sections: disclosure issues, testing issues, exposure management, and curriculum modification and prevention. PMID- 11765248 TI - Use of nonvitamin, nonmineral dietary supplements among college students. AB - The authors assessed the use of nonvitamin, nonmineral (NVNM) dietary supplements in a college population. They found that the use of NVNM dietary supplements among college students might be higher than that of other population groups and that the types of NVNM products they use differ from those used by an older population. Of the 272 students who completed the questionnaire, 48.5% reported they took an NVNM supplement during the past 12 months. The most frequently used NVNM products were echinacea, ginseng, and St John's wort. Of the 27 students who took NVNM products to promote weight loss, 81.5% had body mass index (BMI) values in the acceptable range. Eleven of the 19 participants who reported an adverse reaction to an NVNM supplement continued to take the products despite negative effects. Users and nonusers of NVNM supplements did not differ significantly by age, ethnicity, gender, perceived dietary adequacy, or by exercise patterns. PMID- 11765249 TI - Sleep habits and patterns of college students: a preliminary study. AB - The negative effects of sleep difficulties have been well documented. However, the prevalence of such problems among US college students has not been well studied. Design difficulties are common in the limited number of existing investigations, making it difficult to estimates the prevalence and types of disturbance studied. The authors describe the use of a quantitative-based assessment instrument to provide an initial indication of students' sleep problems and to serve as a means of addressing some of the deficiencies in the literature. In their sample of 191 undergraduates at a rural southern university, they found that most of the students exhibited some form of sleep disturbance and that women, in general, reported more sleep disturbances than men did. They suggest how colleges and university officials can alter procedures to minimize students' sleep disturbances and reduce the deleterious effects of sleep problems on academic performance. PMID- 11765250 TI - Using nursing students to enhance one college's immunization program. AB - In New York State, all college students who were born on or after January 1, 1957, are required to show proof of immunity against measles, mumps, and rubella (MMR) before the 1st day of classes. Colleges have established immunization programs so that those students who do not have the required proof can be given the necessary injections. Often, our health service office does not have enough staff to administer the MMR shots during the registration period, resulting in long lines of students waiting to be immunized. In this article, the authors describe how one college used nursing students to assist with and enhance its immunization program. The 45 nursing students who participated in this project administered 694 injections over a 5-day period, They received credit from the nursing department for clinical time and all of the participants agree that the project was a success. PMID- 11765251 TI - Facilitating student use of campus smoking cessation services. PMID- 11765252 TI - Medical service risk and the evolution of provider compensation arrangements. PMID- 11765253 TI - The role of the capital markets in restructuring health care. PMID- 11765254 TI - Arrow and the information market failure in health care: the changing content and sources of health care information. PMID- 11765255 TI - The end of asymmetric information. PMID- 11765256 TI - Managing uncertainty: intermediate organizations as triple agents. PMID- 11765257 TI - Moral hazard vs. real hazard: quality of care post-Arrow. PMID- 11765258 TI - Arrow's analysis of social institutions: entering the marketplace with giving hands? PMID- 11765259 TI - The market for medical ethics. PMID- 11765260 TI - The role of nonprofits in health care. PMID- 11765261 TI - Arrow on trust. PMID- 11765262 TI - From trust to political power: interest groups, public choice, and health care. PMID- 11765263 TI - Regulating health care: from self-regulation to self-regulation? PMID- 11765264 TI - The lawyerization of medicine. PMID- 11765265 TI - Reflections on the reflections. PMID- 11765266 TI - Kenneth Arrow and the changing economics of health care. PMID- 11765267 TI - Kenneth Arrow and the changing economics of health care: "Why Arrow? Why now?". PMID- 11765268 TI - Uncertainty and the welfare economics of medical care. 1963. PMID- 11765269 TI - General equilibrium and marketability in the health care industry. PMID- 11765270 TI - Arrow's concept of the health care consumer: a forty-year retrospective. PMID- 11765271 TI - Uncertainty and technological change in medicine. PMID- 11765272 TI - Human inputs: the health care workforce and medical markets. AB - Arrow wrote his classic article in simpler times, as those who chance upon this article forty years hence will say of today. It was a new era in science and medicine, soon to be fueled by new resources from Medicare and the National Institutes of Health. Fiscal constraint was a stranger, physicians were in short supply, and information asymmetry was pervasive. In the intervening years, Americans have become more comfortable with health care issues. Fatal illness, which was rarely discussed with patients in 1960, is now researched by them on the Internet, and greater attention is paid to patient rights. Nonetheless, concerns about quality have, if anything, increased. Indeed, it is public concern about quality that has invited governmental regulation and induced a defensive posture among medical organizations, which are rushing to establish their own instruments of quality, and it is these same public concerns that have facilitated the ability of managed care to offer itself as the guarantor of quality. However, center stage is now held by another issue: health care costs. As a result, the focus has shifted from resolving information asymmetry by enhancing quality to controlling national health expenditures by changing the size and composition of the health care workforce. Licensure, which was restrictive in 1960, is more relaxed today, thereby reducing the entry barriers for the NPC disciplines, several of which were just beginning when Arrow wrote his article. The entry of NPCs into the realm of physician's services partially counterbalances the constraints that have been placed on physician supply, although the major contributions of NPCs are skewed to the primary care end of the spectrum while the major constraints on physician supply affect specialists. The growing presence of NPCs creates a dynamic market in which practitioners in various disciplines both compete and collaborate. It is, in fact, the perfect market that Arrow reluctantly longed for, in which providers who have different levels of skill offer their services at varying prices. But consumers have little upon which to base their choices. And while many of the services offered by NPCs replace physician services at a lower price, others represent additional services, which add to aggregate spending. Arrow sought to explain how a market replete with uncertainty could function. He saw that licensure, entry rationing, and educational subsidies could work to enhance quality, but they did so at the expense of the market. The market has seen it differently and has usurped these tools for its own purposes, leaving quality to look for other sponsors. Has it done so wisely? We have yet to see how well a multidisciplinary workforce of autonomous providers will function, but both successes and failures abound. What is more apparent is how entry rationing and restrictions on educational subsidies have capped the supply of physicians and limited the production of specialists at a time when there is increasing demand for their services. Arrow identified potent tools for affecting the characteristics of the health care workforce. They now must be redirected to the needs of the future. PMID- 11765273 TI - Health care as a (big) business: the antitrust response. PMID- 11765274 TI - Health insurance and market failure since Arrow. PMID- 11765275 TI - Can efficiency in health care be left to the market? PMID- 11765276 TI - Valuing charity. AB - Arrow asserted that a variety of institutional arrangements and observable mores of the medical profession were functional responses to the failure of the market to insure against uncertainties. But one of these norms--the ethic to provide treatment without regard to ability to pay--was also a response to the failure of the political system to assure the elderly and poor would not suffer more than others when they got sick. This ethic is strikingly different from the norm in most other areas of the economy. Automobile dealers and department stores are not expected to give away their products to the poor; neither are grocery stores or farmers. Public education is a closer analogy, reflecting the norm that all children deserve a good education. In education, however, unlike in medicine, we collectively support this norm by providing public funds to accomplish this goal rather than by relying on the private market. In 1963, physicians argued that a combination of the market and private philanthropy (including the obligations of physicians) would be sufficient to guarantee high-quality care for the elderly and the poor. Government financing, they argued, would lead to socialized medicine, impairing relationships between physicians and patients and between physicians and society. Based on his article, Arrow would not have agreed. Neither, apparently, did the public. The enactment of Medicare indicated, in part, that many people understood, even in 1965, the extent to which treatment choices and outcomes were affected by ability to pay. Events since 1965 suggest that there is some tension between insurance and ethical responses to uncertainty despite Arrow's endorsement of both. I have argued here that Medicare and Medicaid further eroded the ethic that treatment should be available without regard to ability to pay by reducing physician willingness to provide charity care and by reducing the resources available to public hospitals and the interest of private teaching hospitals in providing care to the uninsured poor. Largely independent of Medicare and Medicaid, the increasing importance of pharmaceuticals and other services delivered outside of the hospital further strengthened the connection between treatment choices and ability to pay, and the growth of capitated payment systems made this connection salient to many insured patients and their physicians. In part, then, the AMA was correct: Medicare and Medicaid have contributed to the erosion of trust in physicians as incorruptible agents for patients. Some of this trust undoubtedly was misplaced, even in 1965, and trust alone was not sufficient to guarantee widespread access to medical care or to assure that treatment provided would take true social benefits and costs into account. Medicare and Medicaid, as well as the growth of prepayment insurance plans, represent institutional responses to the failure of the 1963 norms to accomplish societal goals. Still, as we have seen, these responses create their own challenges, and we continue to search for institutions that will allow widespread insurance to coexist with the physician-patient trust that Arrow correctly identified as an important response to uncertainties and information asymmetries in the medical care market. PMID- 11765277 TI - Hyperactivity in preschool children is highly heritable. PMID- 11765278 TI - Topiramate for reversing atypical antipsychotic weight gain. PMID- 11765279 TI - SSRIs associated with behavioral activation and suicidal ideation. PMID- 11765280 TI - Schizotypal disorder among child and adolescent mental health services users. PMID- 11765281 TI - Longitudinal study of maternal depressive symptoms and child well-being. AB - OBJECTIVE: To investigate whether prenatal, postnatal, and/or current maternal depressive symptoms are associated with low level of psychosocial functioning or high level of emotional/behavioral problems in school-age children. METHOD: As part of a prospective longitudinal study, maternal depressive symptoms were screened with the Edinburgh Postnatal Depression Scale prenatally, postnatally, and when the children were 8 to 9 years old. The original sample of 349 mothers was collected in 1989-1990 in Tampere, Finland. Of the 270 mother-child pairs at the latest stage of the study in 1997-1998, 188 mother-child pairs participated and 147 were included. The associations between maternal depressive symptoms at different points in time and the level of children's psychosocial functioning and problems reported on the Child Behavior Checklist and Teacher's Report Form were examined. RESULTS: Children's low social competence and low adaptive functioning were associated with concurrent maternal depressive symptoms. Maternal postnatal depressive symptoms predicted low social competence. The presence of prenatal depressive symptoms in the mother was a strong predictor of child's high externalizing and total problem levels (odds ratio 3.1, 95% confidence interval 1.1-8.9 and odds ratio 8.5, 95% confidence interval 2.7-26.5). Prenatal as well as recurrent maternal depressive symptoms were associated with the least favorable child outcome. CONCLUSIONS: Maternal depressive symptomatology at any time, especially prenatally, is a risk factor for the child's well-being. This should be noted already in prenatal care. The timing and the recurrence of maternal depressive symptoms affect the outcome for the child. PMID- 11765282 TI - Infant mental health and variability of parental depression symptoms. AB - OBJECTIVE: To examine the course of mothers' depression symptoms in association with child and family functioning beyond that explained by diagnostic status. METHOD: A longitudinal high-risk design with 16 months of course-of-illness follow-up was used. Structured clinical and family interviews, direct observation of child social-emotional competence, and parent reports of child behavior problems were included. RESULTS: Parameters of maternal symptom patterns across time were associated with child and family functioning. Most of these effects remained when presence/absence of major depression diagnosis was covaried. CONCLUSIONS: The trajectory of symptoms over time is important to consider in studies of children at risk and may also help to inform how illness in infancy and early childhood is conceptualized. PMID- 11765283 TI - DSM-IVSymptoms in community and clinic preschool children. AB - OBJECTIVE: To describe and compare ratings of psychiatric symptoms in community and clinic samples (ages 3-6 years) using a DSM-IV-referenced rating scale. METHOD: Parent (/and teacher) ratings were obtained for community (N = 531/398) and special education (N = 64/140) samples (1995-1997) and an outpatient clinic (N = 224/189) sample (1994-1996). RESULTS: Age and socioeconomic status were only minimally (r< 0.20) correlated with ratings of psychopathology. The most commonly endorsed symptom categories were attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, anxiety disorder, conduct disorder (teacher), and pervasive developmental disorder (clinic). Groups were easily differentiated by the rate and severity of symptoms (clinic > special education > community). Males generally received higher scores than females (especially teacher ratings). Children with ADHD symptoms had higher ratings of impairment (developmental deficits) than the non-ADHD group. CONCLUSIONS: Although these findings share a number of similarities with studies of older children, there are also differences that attest to the uniqueness of this age group. PMID- 11765284 TI - Oppositional defiant disorder with onset in preschool years: longitudinal stability and pathways to other disorders. AB - OBJECTIVE: To examine the stability and change in oppositional defiant disorder (ODD) with onset among preschool children in a pediatric sample. METHOD: A total of 510 children aged 2-5 years were enrolled initially in 1989-1990 (mean age 3.42 years); 280 participated in five waves of data collection over a period of 48 to 72 months (mean wave 5 age, 8.35 years). Test batteries varied by age, but they included the Child Behavior Checklist, developmental evaluation, Rochester Adaptive Behavior Inventory, and a play session (before age 7 years) and a structured interview (Diagnostic Interview for Children and Adolescents, parent and child versions) at ages 7+ years. Consensus diagnoses were assigned by using best-estimate procedures. RESULTS: Wave 1 single-diagnosis ODD showed a significant relationship with both single-diagnosis ODD and single-diagnosis attention-deficit hyperactivity disorder (ADHD) at subsequent waves, but not with single-diagnosis anxiety or mood disorders. Single-diagnosis ODD at wave 1 was associated with later comorbidity of ODD/ADHD, ODD/anxiety, and ODD/mood disorders. Stability across waves 2 through 5 was moderate to high for comorbid ODD/anxiety and ODD/ADHD; low to moderate stability for single-diagnosis ODD and single-diagnosis mood disorder; and low for mood disorder, single-diagnosis ADHD, and single-diagnosis anxiety disorder. CONCLUSIONS: Preschool children with ODD are likely to continue to exhibit disorder, with increasing comorbidity with ADHD, anxiety, or mood disorders. PMID- 11765285 TI - Child psychiatric diagnoses in a population of Dutch schoolchildren aged 6 to 8 years. AB - OBJECTIVE: To determine the prevalence rates of child psychiatric diagnoses in a school-based population of children aged 6 to 8 years in the south of the province of Limburg (The Netherlands). METHOD: In a two-stage design 1,317 children were screened with the Child Behavior Checklist. From 403 of these children, child psychiatric information was obtained with the Amsterdam Diagnostic Interview for Children and Adolescents (ADIKA, DSM-III-R/IV). Data were generalized to the responder group (n = 1,317) and to the entire cohort (N = 2,290). For the latter procedure, a prediction model was used to generalize ADIKA results to the nonresponders (n = 973). RESULTS: Estimates of the prevalence of different ADIKA diagnoses in the responder group were quite comparable with those for the entire cohort. Twenty-four percent of the entire cohort met criteria for a single disorder, and 21.0% met criteria for two or more disorders. However, in only 5.7% of the cases parents did report a need for help. CONCLUSIONS: Where other studies generalize psychiatric diagnoses to the responder group only, this report adds new information by generalizing the prevalence to a school-based cohort of children aged 6 to 8 years. These prevalence estimates are of importance with regard to the demand for care for child psychopathology. PMID- 11765286 TI - Validity of DSM-IVADHD subtypes in a nationally representative sample of Australian children and adolescents. AB - OBJECTIVE: To examine the discriminant validity of DSM-IV attention deficit/hyperactivity disorder (ADHD) subtypes in a nationally representative sample of Australian youths. METHOD: The Diagnostic Interview Schedule for Children, including the symptom-specific impairment questions, was administered to 3,597 parents of children aged 6 to 17 years (response rate = 70%). Parents also completed questionnaires assessing children's emotional and behavioral problems and quality of life. RESULTS: Current DSM-IVADHD prevalence was 7.5% (6.8% with impairment) with inattentive types being more common than hyperactive impulsive and combined types. ADHD was more prevalent among young males and was linked to social adversity, particularly for combined types. Compared with non ADHD controls, all three ADHD subtypes were rated as having more emotional and behavioral problems and lower psychosocial quality of life, with combined types consistently rated the most impaired. Combined types received higher ratings than hyperactive-impulsive and inattentive types on externalizing behavior problems, disruption to family activities, and symptom-specific impairments with schoolwork and peer-related activities. Inattentive types were rated as having lower self esteem, more social and school-related problems, but fewer externalizing problems than hyperactive-impulsive types. CONCLUSION: These findings support the view of DSM-IVADHD subtypes as distinct clinical entities with impairments in multiple domains. PMID- 11765287 TI - Screening for conduct problems: does the predictive accuracy of conduct disorder symptoms improve with age? AB - OBJECTIVES: To investigate the influence of age on the predictive accuracy of conduct disorder (CD) symptoms for future CD and to evaluate the usefulness of CD symptoms as a screening tool in normal populations. METHOD: Two cohorts were derived from the Canadian National Longitudinal Survey of Children and Youth based on age at baseline (cohort 1: ages 5-6, n = 881; cohort 2: ages 8-9, n = 859). CD symptoms were assessed with behavior symptom checklists at baseline and the 2-year follow-up assessment. Predictive accuracy (PA) was evaluated with logistic regression and receiver operating characteristic curves. RESULTS: The PA of teacher-identified CD symptoms, alone or in combination with other risk factors (gender, socioeconomic status, familial factors), was higher in the older cohort. PA increased when CD symptoms were combined with other risk factors. However, none of the predictors evaluated achieved minimum criteria for sensitivity and positive predictive value of at least 50%. CONCLUSIONS: The PA of CD symptoms improves with age. However, the results show that the PA of CD symptoms assessed at a single point in time in children in normal populations is insufficient. Screening initiatives that use this approach to detect risk for CD should be abandoned. PMID- 11765288 TI - Major depression and drug disorders in adolescence: general and specific impairments in early adulthood. AB - OBJECTIVE: To identify adulthood impairments associated with major depression and drug disorders in adolescence, distinguishing between general impairments for both disorders and specific impairments for each disorder. METHOD: Within a longitudinal community study (N= 365), the Diagnostic Interview Schedule provided 1-year diagnoses of major depression and drug abuse/dependence at age 18. At age 21, current functioning was assessed. RESULTS: Adolescents with either depression or drug disorders had substantial deficits in later functioning, with few impairments shared in common. General areas of impairment included lower global functioning, externalizing behavior problems, and suicidal behaviors. Difficulties specific to depression encompassed multiple internalizing problems: interpersonal difficulties, decreased psychological well-being, career dissatisfaction, and active major depression at age 21. For males only, overall poor health was also a specific depression outcome. Age 21 problems unique to drug disorders included lower likelihood of post-high school education, being fired, and active drug disorders. Males, but not females, were also more likely to report antisocial behaviors in adulthood. CONCLUSIONS: Despite several significant commonalities, including suicide attempts, deficits associated with depression and drug disorders were primarily specific, suggesting distinct trajectories. Results highlight the need for specific follow-up services to alleviate continuing problems associated with these disorders. PMID- 11765289 TI - Longitudinal relationships between childhood, adolescent, and adult eating disorders. AB - OBJECTIVE: This study investigates the longitudinal course of eating problems from childhood though adulthood. The following questions are answered: (1) How stable are eating disorder symptoms and diagnoses over a 17-year interval from childhood to adulthood? (2) Do early childhood eating problems predict the occurrence of eating disorders in adulthood? METHOD: An epidemiologically selected sample of approximately 800 children and their mothers received DSM based structured psychiatric assessments in 1975, 1983, 1985, and 1992. The stability of full DSM diagnostic criteria for anorexia nervosa and bulimia nervosa, symptom scales derived from DSM criteria, and individual symptoms such as binge eating or dieting between early adolescence, late adolescence, and young adulthood was examined. RESULTS: Early adolescent bulimia nervosa is associated with a 9-fold increase in risk for late adolescent bulimia nervosa and a 20-fold increase in risk for adult bulimia nervosa. Late adolescent bulimia nervosa is associated with a 35-fold increase in risk for adult bulimia nervosa. Symptom scale scores for anorexia nervosa and bulimia nervosa correlate in the 0.3 to 0.5 range from early to late adolescence and young adulthood. For both anorexia nervosa and bulimia nervosa, gender, as well as eating symptoms at early and late adolescence, all predict young-adult eating disorder symptoms. Risk factors for the later development of eating disorders comprise eating conflicts, struggles with food, and unpleasant meals in early childhood. CONCLUSION: The presence of eating problems in early childhood or an eating disorder in adolescence confers a strong risk for an eating disorder in young adulthood. PMID- 11765290 TI - Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder. AB - OBJECTIVES: To examine the relationship between age and short-term clinical response to psychostimulant treatment in youths with attention deficit/hyperactivity disorder (ADHD) and to examine whether weight-corrected doses of optimized psychostimulant therapy varied as a function of patient age. METHOD: One hundred seventy-seven patients were treated with either methylphenidate (MPH) or Adderall (ADL). Sixty-six youths received ADL and 111 patients were treated with MPH. All youths were evaluated at baseline and after receiving a week of treatment at each blinded, randomized dose level (placebo, 5, 10, or 15 mg). A "best dose" for each patient was assigned before the medication blind was broken. Behavioral ratings by both teachers and parents were examined for dose and medication effects. RESULTS: The medications had similar efficacy in children and teenagers. Older youths, however, benefited from a smaller weight adjusted dose of medication than did the younger children. Similar efficacy was observed between the medications. CONCLUSIONS: These data suggest that psychostimulants are equally effective in treating children and adolescents with ADHD. Adolescents with ADHD may not necessarily require more medication than younger children to achieve a similar therapeutic response. PMID- 11765291 TI - Adjunctive antipsychotic treatment of adolescents with bipolar psychosis. AB - BACKGROUND: A combination of an antipsychotic medication and a mood stabilizer is often used for initial treatment of acute psychotic mania. However, the optimal duration of this adjunctive antipsychotic medication is unknown. METHOD: As part of a lithium efficacy study, acutely manic adolescents with psychotic features were given open combination treatment with lithium and an adjunctive antipsychotic medication. If the psychosis resolved, the antipsychotic medication dose was gradually tapered and discontinued after 4 weeks of therapeutic lithium levels. The subject was then given a trial of maintenance lithium monotherapy for up to 4 weeks. RESULTS: Significant improvement was seen in 64% of the sample with psychotic features after 4 weeks of combination treatment. However, few maintained their response after discontinuation of the antipsychotic medication. Successful discontinuation of antipsychotic medication in this sample was associated with first episode, shorter duration of psychosis, and the presence of thought disorder at baseline. CONCLUSIONS: Adjunctive antipsychotic medication needs to be maintained for longer than 4 weeks in the vast majority of adolescents with psychotic mania, even though the manic and psychotic symptoms have resolved and lithium treatment is maintained. Future studies to determine the optimal duration of adjunctive antipsychotic medication treatment are warranted. PMID- 11765292 TI - Can the checklist for autism in toddlers differentiate young children with autism from those with developmental delays? AB - OBJECTIVE: The Checklist for Autism in Toddlers (CHAT) has been demonstrated to be sensitive to the presence of autism in otherwise normally developing 18-month old children. However, its ability to differentiate autism from other significant developmental delays is unknown. This study examined this question. METHOD: The CHAT was applied to a group of 44 children aged 2 and 3 years, rigorously diagnosed with autism or with other developmental problems. RESULTS: By the original CHAT authors' criteria, the sensitivity and specificity of the CHAT were 65% and 100%, respectively. Slightly altering the criteria resulted in a sensitivity of 85% in the current group of children with developmental disabilities while maintaining specificity of 100%. CONCLUSIONS: The current study is the first to demonstrate that the CHAT successfully discriminates 2-year old children with autism from those with other developmental disorders. In addition, the increased sensitivity of the Denver Criteria in children with developmental disabilities may improve its usefulness as a screening tool for community-based early-diagnostic teams and general practitioners. PMID- 11765293 TI - Oculomotor abnormalities in boys with tourette syndrome with and without ADHD. AB - OBJECTIVE: To assess saccadic eye movements in boys with Tourette syndrome (TS) with and without attention-deficit hyperactivity disorder (ADHD), comparing performance with that of an age-matched group of male controls. METHOD: Three different saccade tasks (prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and execution of eye movements, including motor response preparation, response inhibition, and working memory. The study included 14 boys with TS without ADHD (TS-only), 11 boys with TS and ADHD (TS+ADHD), and 10 male controls. RESULTS: Latency of prosaccades was prolonged in boys with TS (both with and without ADHD) compared with controls. Variability in prosaccade latency was greater in the groups of boys with TS+ADHD compared with both the TS-only and control groups. Response inhibition errors on both the antisaccade task (directional errors) and memory-guided saccade task (anticipatory errors) were increased in boys with TS+ADHD compared with those with TS-only. There were no significant differences among the three groups in accuracy of memory-guided saccades. CONCLUSIONS: Oculomotor findings suggest that TS is associated with delay in initiation of motor response as evidenced by excessive latency on prosaccades. Signs of impaired response inhibition and variability in motor response appear to be associated with the presence of ADHD. PMID- 11765294 TI - Psychiatric consultation to school-based health centers: lessons learned in an emerging field. PMID- 11765295 TI - Ethical issues related to publishing and reviewing. PMID- 11765296 TI - Genetics of childhood disorders: XXXIII. Autoimmunity, part 6: poststreptococcal autoimmunity. PMID- 11765297 TI - Impact of the cost of prescription drugs on clinical outcomes in indigent patients with heart disease. AB - STUDY OBJECTIVE: To measure the impact that economic relief for prescription drugs to indigent patients with cardiovascular disease has on indicators of disease control. DESIGN: Prospective cohort study. SETTING: University inner-city outpatient clinic. PATIENTS: One hundred sixty-three indigent patients with heart disease who were uninsured or whose insurance plan did not provide prescription drug coverage and who had baseline data. INTERVENTION: Patients were assisted in obtaining prescription drugs, free of charge, in an attempt to improve adherence to their drug regimens. MEASUREMENTS AND MAIN RESULTS: The primary end point was to determine if cardiovascular outcome measures (i.e., international normalized ratio [INR], blood pressure, low-density lipoprotein [LDL] cholesterol, and hospitalizations) and drug adherence improved in all patients after 6 months of prescription assistance compared with a 6-month baseline period. In patients receiving warfarin, mean INR increased from 2.44 +/- 0.64 at baseline to 2.61 +/- 0.53 at 6 months (p<0.05). In patients with hypertension, mean blood pressure decreased from 138 +/- 20/80 +/- 11 mm Hg at baseline to 138 +/- 19/78 +/- 12 mm Hg at 6 months (p<0.05 for diastolic blood pressure only). The mean LDL level for patients on lipid-lowering drugs significantly decreased from 126 +/- 39 mg/dl at baseline to 108 +/- 38 mg/dl at 6 months (p<0.001). For each disease measure, the improved disease control seen at 6 months persisted throughout 24 months of follow-up. Hospitalizations for the entire cohort decreased from 85 at baseline to 49 at 6 months. Patient drug adherence improved from 48.5% at baseline to 72.7% at 6 months (p<0.001). CONCLUSIONS: Drug adherence and clinical outcomes improved, and the number of hospitalizations declined when cardiovascular drugs were obtained for patients who could not afford to pay for them. Health care insurance plans that do not provide coverage for cardiovascular prescription drugs may be more costly secondary to poor disease control and increased hospitalizations. PMID- 11765298 TI - Adherence to oral montelukast and inhaled fluticasone in children with persistent asthma. AB - STUDY OBJECTIVE: To evaluate adherence to oral montelukast and inhaled fluticasone in children with persistent asthma and to determine if age, monotherapy, and duration of therapy affect adherence. DESIGN: Retrospective analysis. SETTING: Pediatric pulmonary clinic. PATIENTS: One hundred seventy-one children with asthma who required continuous treatment with a controller agent year-round and in whom montelukast and/or fluticasone had been prescribed for at least 90 days. INTERVENTION: Montelukast monotherapy had been prescribed for 54 patients, fluticasone monotherapy for 48 patients, and combination therapy for 69 patients. MEASUREMENTS AND MAIN RESULTS: Prescription refill histories were obtained from pharmacies identified by the parents or from Medicaid pharmacy reimbursement records. The maximum possible adherence was calculated as [(no. of doses refilled)/(no. of doses prescribed)] x 100, for a mean observation period of 203 days (range 84-365 days) for montelukast and 314 days (range 97-365 days) for fluticasone. Median adherence rates were 59% (95% confidence interval [CI] 48 65%) for montelukast and 44% (90% CI 35-50%) for fluticasone. Adherence did not significantly correlate with age, length of observation period, or whether the patient was receiving monotherapy or combination therapy. The odds ratio for very poor adherence (< 50%) was 2.0 (95% CI 1.3-3.2) for fluticasone relative to montelukast. CONCLUSIONS: Adherence to both drugs was suboptimal. However, these data indicate that our patients were likely to take montelukast more consistently than fluticasone. Whether this translates into better asthma control requires further study. PMID- 11765299 TI - Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. AB - STUDY OBJECTIVE: To compare the rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin administration. DESIGN: Retrospective database analysis. INTERVENTION: Evaluation of reported rates of torsades de pointes in patients who received these quinolones between January 1, 1996, and May 2, 2001. MEASUREMENTS AND MAIN RESULTS: In the United States, 25 cases of torsades de pointes associated with these quinolones (ciprofloxacin 2, ofloxacin 2, levofloxacin 13, gatifloxacin 8, moxifloxacin 0) were identified. Ciprofloxacin was associated with a significantly lower rate of torsades de pointes (0.3 cases/10 million prescriptions, 95% confidence interval [CI] 0.0-1.1) than levofloxacin (5.4/10 million, 95% CI 2.9-9.3, p<0.001) or gatifloxacin (27/10 million, 95% CI 12-53, p<0.001 for comparison with ciprofloxacin or levofloxacin). When the analysis was limited to the first 16 months after initial U.S. approval of the agent, the rates for levofloxacin (16/10 million) and gatifloxacin (27/10 million) were similar (p>0.5). CONCLUSION: Levofloxacin should be administered with caution in patients with risk factors for QT prolongation. Gatifloxacin should be avoided in the same patient population, and the recommended dosage of 400 mg/day should not be exceeded. PMID- 11765300 TI - Cholesterol and glycemic effects of Niaspan in patients with type 2 diabetes. AB - STUDY OBJECTIVE: To determine the effect of Niaspan--a niacin preparation with both immediate- and extended-release characteristics--on lipid and glycemic control in patients with type 2 diabetes. DESIGN: Retrospective study SETTING: Private-practice endocrinology group. PATIENTS: Thirty-two patients (mean age 60 yrs; 72% men) with type 2 diabetes identified by a computerized text search. INTERVENTION: Patients received Niaspan 1000, 1500, or 2000 mg/day (median daily dosage 1000 mg). MEASUREMENTS AND MAIN RESULTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hemoglobin A1c, and transaminase levels were compared for each patient before and 6 months after initiation of Niaspan. Niaspan therapy was associated with a significant 34% increase in HDL (p=0.033), a significant 36% reduction of triglycerides (p=0.049), and no significant change in LDL (p=0.236) or total cholesterol (p=0.122). Mean hemoglobin A1c levels significantly decreased from baseline by 0.5 +/- 0.3% (p=0.032), even though dosages and treatment with antidiabetic agents remained constant. There were no significant changes in transaminase levels. Seven patients (21.9%) discontinued Niaspan; one of them experienced an increase in blood glucose while receiving the agent. CONCLUSION: For most patients with type 2 diabetes, Niaspan is a safe and effective therapy for dyslipidemia and does not exacerbate glycemic control. PMID- 11765301 TI - In vitro pharmacodynamic analysis of single daily dosing versus conventional dosing of gentamicin administered with penicillin against Enterococcus faecalis. AB - STUDY OBJECTIVE: To compare the effectiveness of single daily dosing (SDD) versus conventional dosing of gentamicin when administered with penicillin to treat enterococcal infections. DESIGN: In vitro pharmacodynamic model. SETTING: Hospital laboratory. MEASUREMENTS AND MAIN RESULTS: A 24-hour in vitro pharmacodynamic model was employed to simulate SDD and 3 times/day dosing of gentamicin, in conjunction with continuously infused penicillin, against Enterococcus faecalis. Duplicate 24-hour kill curves were generated with varying concentrations of penicillin and gentamicin alone and in combination. No difference in the rate of kill was seen between any combination of penicillin and gentamicin. Regrowth occurred only with drug combinations in which penicillin was administered continuously at the minimum inhibitory concentration. Variations in the gentamicin dosing regimen did not affect regrowth. CONCLUSION: In the treatment of enterococcal infections, an SDD regimen for gentamicin shows no efficacy benefit compared with conventional dosing. PMID- 11765302 TI - A comprehensive review of MDMA and GHB: two common club drugs. AB - "Club drugs" have become alarmingly popular. The use of 3,4 methylenedioxymethamphetamine (MDMA, Ecstasy) and gamma-hydroxybutyrate (GHB), in particular, has increased dramatically from 1997-1999. The pharmacokinetics of MDMA and GHB appear to be nonlinear, making it difficult to estimate a dose response relationship. The drug MDMA is an amphetamine analog with sympathomimetic properties, whereas GHB is a gamma-aminobutyric acid analog with sedative properties. Symptoms of an MDMA toxic reaction include tachycardia, sweating, and hyperthermia. Occasional severe sequelae include disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Treatment includes lowering the body temperature and maintaining adequate hydration. Symptoms of GHB intoxication include coma, respiratory depression, unusual movements, confusion, amnesia, and vomiting. Treatment includes cardiac and respiratory support. Because of the popularity of these agents and their potentially dangerous effects, health care professionals must be familiar with these substances and the treatment options for patients who present with symptoms of a toxic reaction. PMID- 11765303 TI - A review of class III antiarrhythmic agents for atrial fibrillation: maintenance of normal sinus rhythm. AB - A noteworthy shift from class I to class III antiarrhythmic agents for suppression of atrial fibrillation has occurred. Sotalol, amiodarone, and dofetilide have been evaluated for their ability to maintain sinus rhythm in patients with chronic atrial fibrillation. All of these agents are moderately effective; however, amiodarone appears to be most efficacious. Aside from their common class III actions, these agents have profoundly different pharmacologic, pharmacokinetic, safety, and drug interaction profiles that help guide drug selection. Amiodarone and dofetilide are safe in patients who have had a myocardial infarction and those with heart failure. The safety of commercially available d,l-sotalol in these patients is poorly understood. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide, and risk increases with renal dysfunction. Amiodarone has minimal proarrhythmic risk but has numerous noncardiac toxicities that require frequent monitoring. Overall, an ideal antiarrhythmic agent does not exist, and drug selection should be highly individualized. PMID- 11765304 TI - Effect of nonnicotine pharmacotherapy on smoking behavior. AB - Smoking-related disease is the single biggest preventable cause of morbidity and mortality in the United States, yet approximately 25% of Americans continue to smoke. Various dosage forms of nicotine replacement therapy increase smoking quit rates relative to placebo, but they generally do not result in 1-year quit rates of over 20%. To increase these rates, a number of nonnicotine agents have been investigated. Drugs that modulate noradrenergic neurotransmission (bupropion, nortriptyline, moclobemide) are more effective than those affecting serotonin (selective serotonin reuptake inhibitors, buspirone, ondansetron) or other neurotransmitters. PMID- 11765305 TI - Pancreatitis associated with valproic acid: a review of the literature. AB - Black box warnings for valproic acid caution clinicians of the potential for fatal hepatotoxicity and teratogenicity. Since 1979, case reports of pancreatitis induced by valproic acid have been published in the medical literature. As a result, pancreatitis was added to the black box warnings for valproic acid. We performed searches of MEDLINE and International Pharmaceutical Abstracts and found valproic acid-induced pancreatitis in 45 patients from 31 published articles. Demographics, clinical characteristics, and outcomes of these patients are summarized. Recommendations for monitoring the potential for pancreatitis to develop in patients receiving valproic acid therapy are described, as are potential mechanisms for inducement of pancreatitis by valproic acid. PMID- 11765306 TI - Ecstasy: dangers and controversies. AB - Ecstasy is a recreational drug that is increasing in popularity, particularly in young adolescents. Its appeal involves its euphoric effects and a feeling of empathy for others (hence the nickname "hug drug"). This appeal may be furthered by a misleading and anecdotal perception of safety. Cases of adverse effects, toxic reactions, and fatalities are increasingly being reported in the medical literature, as well as in the popular press. Adverse effects include hyperthermia, seizures, cardiac abnormalities, and hyponatremia. Long-term Ecstasy use may result in serotonin terminal degeneration and depletion, which may result in psychiatric and cognitive sequelae. Controversy surrounds the legalization of Ecstasy for medicinal purposes. PMID- 11765307 TI - Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. AB - STUDY OBJECTIVE: To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome. DESIGN: Retrospective analysis. SETTING: Pediatric intensive care unit (PICU) in a tertiary care children's hospital. PATIENTS: Twenty-two children (aged 6.1 +/- 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer. INTERVENTION: Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter. MEASUREMENTS AND MAIN RESULTS: Children received fentanyl by continuous infusion for 17.8 +/- 8.4 days. Peak fentanyl infusion rate was 5.9 +/ 3.8 microg/kg/hour, and the median cumulative dose was 1302 microg/kg (range 354 7535 microg/kg). Methadone 0.50 +/- 0.22 mg/kg/day was begun 1.6 +/- 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 +/- 3.6 microg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0-11.9 days). Twenty-one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 +/- 11.9 days without precipitating opioid abstinence syndrome. CONCLUSION: Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome. PMID- 11765308 TI - Evaluation of the association between St. John's wort and elevated thyroid stimulating hormone. AB - STUDY OBJECTIVE: To evaluate whether St. John's wort is associated with an elevation in thyroid-stimulating hormone (TSH) levels. DESIGN: Retrospective case control study SETTING: Hamilton, Ontario; September 1998-May 1999. SUBJECTS: Thirty-seven subjects with elevated TSH levels and 37 age- (+/- 6 yrs) and gender matched subjects with normal TSH levels who resided in the same region. MEASUREMENTS AND MAIN RESULTS: Exposure to St. John's wort during the 3-6 months before TSH measurement was assessed through a telephone interview. A total of 4 of 37 subjects with elevated TSH levels and 2 of 37 subjects with normal TSH levels had taken St. John's wort in that time period. The odds ratio for elevated TSH levels associated with taking St. John's wort was 2.12 (95% confidence interval [CI] 0.36-12.36). CONCLUSION: This study suggests a probable association between St. John's wort and elevated TSH levels. However, because of the wide CIs surrounding the point estimate (which crosses unity), further investigation, including a large, prospective cohort study, is warranted. PMID- 11765309 TI - Gatifloxacin-associated acute hepatitis. AB - Gatifloxacin, a fluoroquinolone with extended gram-positive activity, has become extensively used in both the community and hospital environments. Unfortunately, concerns have been raised about the use of certain fluoroquinolones because of adverse drug reactions. A 44-year-old woman developed acute hepatitis while receiving gatifloxacin for chronic sinusitis. After 5 days of receiving antibiotics, the patient developed nausea, lethargy, and abdominal pain, all of which progressed over the next few days. Liver function tests were elevated, with bilirubin peaking at 9.4 mg/dl. The patient also became jaundiced. A percutaneous liver biopsy showed acute hepatitis with eosinophilic infiltrates consistent with drug-induced hepatitis. All other drugs and disease processes were ruled out as likely causes of the patient's hepatitis. Clinicians should be alerted to the possibility that hepatitis may occur with gatifloxacin administration. PMID- 11765310 TI - Do hypolipidemic drugs lower medical expenses? PMID- 11765311 TI - Theorising the social within physician decision making. AB - Explores the underlying behavioral processes influencing the clinical behavior of physicians toward their patients. Utilizing educational and social influence explanatory models as a baseline, we sought how each, through peer group settings, would affect clinical specific practice decisions. Focusing on family physicians in Israel who were engaged in ongoing professional peer group meetings, it is suggested that health decisions affecting clinical practice are not universal but particularistic and depend a great deal on the transfer of clinical knowledge through selective social networks. Health managers, utilizing these findings, can therefore intervene in the formation of clinical practice decisions. This can be done primarily through management policy to induce the formation of specific types of peer group social networks. PMID- 11765312 TI - Health care management: models for evidence-based practice. AB - Presents models suggesting how research evidence can best be operationalised within health care commissioning. Models were derived from data gathered from surveys of Scottish health board managers and GP fundholders regarding the use of information in commissioning from 1995 to 1997. Feedback on the models was obtained subsequently from practitioners in 1998. Two models, one for health board managers and the other for GPs, are presented. These include critical success factors in achieving evidence-based commissioning and factors that are likely to predispose and precipitate evidence-based practice. Given a culture demanding transparency, accountability and continuing improvement, the models provide tools for reflection, evaluation and planning. In addition, they identify a pragmatic role for managers in evidence-based commissioning and provide a framework for audit. PMID- 11765313 TI - Gatekeeping: a challenge in the management of primary care physicians. AB - Assesses the degree of self-reported implementation of gatekeeping in clinical practice, and gains insight into primary care physicians' attitudes toward gatekeeping and their perceptions of necessary conditions for implementation of gatekeeping in daily practice. A self-administered questionnaire was mailed to a national sample of 800 primary care physicians in Israel, with a response rate of 86 per cent. Multivariate analysis indicated that sick fund affiliation was the main predictor of self-reported implementation of gatekeeping, while specialty training predicted primary care physicians' attitude toward this role. Close communication with specialists, continuous medical education, and management support of physician decisions were identified by respondents as being important conditions for gatekeeping. Discusses strategies to gain the cooperation of primary care physicians, which is necessary for implementing an effective gatekeeping system. PMID- 11765314 TI - First wave PMS pilots: a critical analysis of documentation. AB - Contracts and interim local evaluation reports for the 14 first wave PMS pilots in Northern and Yorkshire region were analysed by documentary analysis. Both contracts and reports were found to vary considerably in size and scope. Most contracts contained aims and objectives that were too broad or vague to guide project management and they lacked useful milestones. This made it difficult to identify criteria for measuring success. The local evaluation reports were also of variable quality. It is recommended that contracts should be accompanied by a development plan containing specific objectives, timescale and process for implementation as well as an evaluation strategy. The relative importance of different targets should be agreed and specified at the outset, to allow weighting of partial success, where some objectives, but not others, are achieved. Project milestones would be made explicit and measurable in the development plan. More clarity in contracts and evaluation for future pilots is essential. PMID- 11765315 TI - Direct integrative practice, time constraints and reactive strategy: an examination of GP therapists' perceptions of their complementary medicine. AB - There has been a movement towards integrating complementary and alternative medicine (CAM) into the NHS and a growing number of general practitioners (GPs) are personally practising CAM to treat their NHS patients (direct integrative practice). While research has begun to examine DIP, time constraints and related issues--of importance not only to practitioners but also to those purchasing and planning health care--have not yet received in depth attention. In response this paper examines GP therapists' experiences of the clinical reality of their DIP. The analysis reveals how a lack of time is perceived by GP therapists as a serious constraint upon their CAM practice and also how they employ a number of strategies in an attempt to overcome such difficulties. PMID- 11765317 TI - Modernisation, the NHS Plan and healthy communities. AB - This paper reviews the NHS Plan from the perspective of the Government's wider programme of "modernising" public services. Although broadly focussed, particularly highlights older people. Two dimensions of modernisation are identified. The NHS Plan is seen to be patient-cited--rather than citizen centred. Argues further, that, if the economic, social and environmental causes of ill health are to be addressed more generally and if citizens are to be enabled to live in healthy, sustainable communities, planning for health services should logically be subordinate to planning for health. Health improvement plans should, therefore, be integrated within the wider community strategies for which local authorities are to have lead responsibility. Similarly, as ill health is recognised to be an important aspect of poverty, inequality and social exclusion, there is a strong case for the integration of the regional offices of the NHSE within the wider structure of regional governance. Finally, the personal social services should ensure that the values of social work and social care are not displaced by medical and nursing models which, historically, have shown little understanding of community development processes. PMID- 11765318 TI - EBM and risk: rhetorical resources in the articulation of professional identity. AB - Evidence-based medicine (EBM) has become a major theme within health care. This has fuelled a significant debate about its role in reducing risk and its possible impact on professional autonomy. Challenges arguments that propose that EBM is a threat to professional power and status by looking at how evidence, risk and professional knowledge come to have meaning. The objective is to deconstruct all three as discursive constructions whose meanings are malleable and embedded in social and power relations. By drawing on sociological debates about the social construction of evidence, risk and professional autonomy indicates the ways in which EBM is neither a rational alternative to the seemingly unending risks of contemporary medicine, nor in opposition to professional status. Instead it concludes by arguing that EBM and notions of risk are rhetorical resources in the articulation of professional autonomy and identity. PMID- 11765319 TI - Can primary care be both patient-centred and community-led? AB - Examines the relationships between the macro-, meso-, and micro-levels in the NHS at the end of the fundholding period and considers their contemporary implications for primary care groups (PCGs) and local health care co-operatives (LHCCs). Fundholding achieved some success in challenging the way in which services were provided at the micro-level (the practice), but had a less marked effect in terms of changing service provision at the health authority (meso-) level or in developing collaborative working with trusts and health authorities in strategic decision making. The health authorities prioritized alternative models of devolved commissioning. Trusts regarded fundholders as a distraction who exerted influence and commanded trust management time disproportionate to their "market share". PCGs and LHCCs represent a shift back to the meso-level in service planning and purchasing. As such there is a risk that the micro-level benefits of fundholding and other forms of devolved commissioning will be lost, while uncertainties remain regarding the capacity of PCGs and LHCCs to incorporate GPs into a collaborative approach to strategic decision making. PMID- 11765320 TI - Managing waiting patients' perceptions: the role of process control. AB - In a study of 195 patients visiting the urgent care department of a hospital in the UK, we examined the effects of three elements of process control on patients' fairness and satisfaction perceptions. Patients who believed they had a voice in the triage process had higher fairness perceptions and waited a shorter period of time than those who believed they did not have a voice in the triage process. In addition, patients who were told the expected waiting time and were kept busy while waiting had higher satisfaction perceptions. We identify implications for hospital employees in managing the patient waiting process. PMID- 11765321 TI - Leadership development in UK companies at the beginning of the twenty-first century: lessons for the NHS? AB - States that the development of leadership in the NHS is currently high on the agenda of the Department of Health, the government and local health sector organisations. Reports the findings of a study of public and private sector organisations, exploring the development of their in-house leadership skills. Outlines the findings in depth and discusses the implications for health organisations. PMID- 11765322 TI - Evaluation of excision, cryosurgery and local BCG vaccination for the treatment of equine sarcoids. AB - Ninety-five horses with sarcoids were subjected to three types of treatment: surgical excision (conventional or carbon dioxide laser), cryotherapy or local BCG vaccination. The type of treatment was selected on the basis of the size, location and clinical appearance of the tumours. The choice between conventional and laser excision was empirical. A successful outcome was obtained in 11 of 14 (79 per cent) of the horses treated by cryosurgery, 18 of 27 (67 per cent) treated by BCG vaccination, 18 of 22 (82 per cent) treated by conventional excision, and 20 of 28 (71 per cent) treated with a carbon dioxide laser. For both excision methods, rigorous measures were taken to avoid autoinoculation and to ensure a wide margin of normal skin. The probability of local recurrence after excision was significantly higher for large sarcoids and sarcoids which had previously failed to respond to treatment. In 10 of the 31 horses with remaining sarcoids, some or all of the untreated sarcoids were observed to regress spontaneously. PMID- 11765323 TI - Influence of three types of farm management on the seroprevalence of Q fever as assessed by an indirect immunofluorescence assay. AB - The influence of three types of farm management on the occurrence of Q fever in cattle was investigated by means of a serological study carried out in Irpinia in southern Italy. Twenty-one herds were permanently housed, 26 were housed in winter and turned out to graze in the spring, and six herds were kept outdoors throughout the year. Blood samples were taken from 1188 cattle and tested by an indirect immunofluorescence assay. The overall seroprevalence of Q fever was 14.4 per cent. The herds which were housed in winter and turned out in the spring had the highest seroprevalence of 19.6 per cent, followed by the permanently housed animals with a seroprevalence of 13.2 per cent and the unhoused cattle had a much lower seroprevalence of 1.9 per cent. PMID- 11765324 TI - Histological evidence of disease in wild stoats (Mustela erminea) in England. AB - Forty-four free-living stoats were collected from five game estates in England and examined for evidence of disease. All the macroscopic lesions were attributable to the trauma associated with being trapped or shot. There were no significant microscopic lesions in 27 (61 per cent) of the stoats. There was evidence of nematode parasitism in the intestines of six stoats (14 per cent), and in the lungs of five stoats (11 per cent), and of pulmonary granulomatous inflammation or microgranulomas in five stoats. In two of the stoats, blood filled cavities in the liver were suggestive of peliosis hepatis, possibly associated with infection by Bartonella species or with sublethal exposure to anticoagulant rodenticides. PMID- 11765325 TI - Observations on the biology and control of the chewing louse (Bovicola limbata) of Angora goats in Great Britain. PMID- 11765326 TI - Pathogens in the reproductive tract of farm rabbits. PMID- 11765327 TI - Establishment of a PRRS virus ELISA-negative boar population using previously exposed boars. PMID- 11765328 TI - Case of malignant biphasic mesothelioma in a dog. PMID- 11765329 TI - Tail-stump defect in the semen of a wild boar. PMID- 11765330 TI - Animal Health Bill. PMID- 11765331 TI - FMD control strategies. PMID- 11765332 TI - Disease surveillance following restocking. PMID- 11765333 TI - Louping ill on Dartmoor. PMID- 11765334 TI - Mouth lesions in sheep. PMID- 11765335 TI - Encephalitozoon cuniculi in rabbits. PMID- 11765336 TI - Haemorrhage following surgery in the spinone. PMID- 11765337 TI - Extramural studies. PMID- 11765338 TI - 'Captain of all these men of death'. The history of tuberculosis in nineteenth and twentieth century Ireland. PMID- 11765339 TI - [The physician facing death]. PMID- 11765340 TI - Management of thyroid cancer. PMID- 11765341 TI - [Papillary microcarcinoma [correction of carcinoma] of the thyroid: clinical experience and prognosis factors]. AB - Thyroid neoplasm of less than 10 mm in the largest diameter are defined as minimal thyroid cancer (MTC). These tumors are a common incidental finding at autopsy and in thyroid glands excised for other pathology. These tumors can metastasize and can cause significant morbidity and mortality. Clinical significance and optimal operative procedures of these lesions are still questioned. We studied 35 MTC in order to identify clinical and histologic characteristics as prognostic factors and to establish therapeutic management strategies. From January 1988 to December 1998, 177 patients with a primary thyroid cancer underwent surgery in the Department of endocrine-surgery of Catholic University in Rome: 35 of them (19.7%) had a MTC. In the post-operative follow-up 13 of the patients with MTC had a lymph node recurrency and/or distant metastases. Careful histologic examination showed multifocality in 12 patients, capsular infiltration in 10 patients and a solid tumor in 9 patients. MTC are common and they are associated with a good prognosis. Our multifactorial analysis has identified as important risk factors: capsular infiltration, solid lesion and multifocal disease. In these cases total thyroidectomy is mandatory. PMID- 11765342 TI - [Familial papillary carcinoma of the thyroid: biogenetic identification and clinical assessment of 4 families]. AB - The Authors report 9 patients who were affected by familial papillary carcinoma of thyroid These patients were members of 4 families and they were selected in a general group of 97 patients affected by papillary cancer of the thyroid who underwent surgery from 1991 to 1998. The 9 patients were 1st degree relatives: two sisters, two sisters, two sisters and three brothers. The clinical course was similar in patients whether familiar or sporadic group, but average age in first was 10 yrs lower than in the latter group. Functional cervical dissection was needed only one time by lymphatic metastasis. Observed survival was 100% (follow up 92-16 months) and no specific complication was reported. Thyreoglobulin value was less than normal in every patients. Ret linkage analysis was always performed and no rearrangement was found; in 4 patients APC gene was detected but it was never seen. Case studies are consistent with an autosomal dominant trait that shows an high penetrance if associated with a permissive codominant trait. The authors believe that are necessary further studies on this occurrence. In papillary thyroid cancer familiarity was observed in 9.6%, than authors propose that relatives of thyroid papillary cancer should be underwent to screening. PMID- 11765343 TI - [Prevention and treatment of intra- and post-operative complications in thyroid surgery]. AB - Frequency of complications in thyroid surgery is evaluated in a series of patients treated during a recent period lasting one year (1997). The records of 455 patients consecutively operated on were analyzed: 396 patients were affected by benign disorders and 59 by thyroid carcinoma. Total thyroidectomy was performed in 158 cases, near subtotal thyroidectomy in 94, thyroid totalization for recurrent disease in 21 and lobectomy in 182 ones. Post-operative haemorrhage, such to require surgical re-exploration of the thyroid bed, occurred in 2 patients (0.4%), both after total thyroidectomy for hyperfunctioning goiter. Recurrent laryngeal lesion has been observed in 2 patients (0.4% of all patients), both after total thyroidectomy for cervico-mediastinal goiter. Transient hypoparathyroidism occurred in 48 patients (10.5%), while definitive one in 9 (1.9%), of which 5 after total thyroidectomy, 2 after subtotal thyroidectomy and 2 after reoperation. Haemorrhage nearly always occurs in the first postoperative hours and gravity is conditioned by tracheal compression exercised by the haematoma. An aspirative drainage located in thyroid bed and a not hermetic closure of the middle line help a precocious diagnosis and sometimes avoid a surgical re-exploration. Some technical surgical devices permit to reduce the risk of inferior laryngeal nerve palsy. Hypoparathyroidism, often transient, is a complication of bilateral thyroid surgery, but unavoidable when more extensive thyroid surgery is required. PMID- 11765344 TI - [Role of Doppler color ultrasonography in the diagnosis of thyroid carcinoma]. AB - The aim of this study is to assess the efficacy and accuracy of color flow Doppler sonography (CFDS) in predicting the malignancy of thyroid nodules. Seventy eight consecutive patients (52 females and 26 males), with 78 thyroid nodules (29 single nodules and 49 in a nodular goiter) have been examined by CFDS, before surgery, evaluating the hypoechogenicity of the nodule, the presence of microcalcifications and the halo sign absent and the vascular pattern, which has been classified as follows: absence of blood flow (type I), perinodular blood flow (type II), intranodular, with or without perinodular blood flow (type III), which is considered the most typical pattern of malignancy. On histology 22 nodules as carcinoma (CA) and 56 as benign nodules (BN) have been diagnosed. The most predictive for malignancy, sonographic pattern, "microcalcifications", has been found in 13/22 CA and in 4/56 BN (P < 0.0001, specificity 93%, sensitivity 59%); "hypoechogenicity" in 16/22 CA and in 8/56 BN (P < 0.0001, specificity 86%, sensitivity 73%), "absent halo sign" in 18/22 CA and in 16/56 BN (P < 0.0001, specificity 71%, sensitivity 82%.) have been found. On CFD type III pattern has been detected in 17/22 CA and in 24/56 BN (P < 0.15, specificity 57%, sensitivity 77%); type IIIa pattern (intranodular without perinodular blood flow) has been the most predictive for malignancy (P < 0.0001, specificity 100%, sensitivity 36%). The combination of type III pattern with "hypoechogenicity" in 13/22 CA and in 2/56 BN (p < 0.0001, specificity 93%, sensitivity 59%) has been found, with "absent halo sign" in 15/22 CA and in 3/56 BN (P < 0.0001, specificity 94.6%, sensitivity 68%), has been found, with "microcalcification" in 10/22 CA and in 0/56 BN (P < 0.0001, specificity 100%, sensitivity 45%) has been found. The combination of "microcalcifications" and absent halo sign" with type III pattern has been the most specific for malignancy, being detected in 11/22 Ca and 2/56 BN (P < 0.0001, specificity 96%, sensitivity 50%). In conclusion our results suggest that CFDS has an useful role in the assessment of thyroid nodules and it may provide information highly predictive for malignancy, above all when multiple, sonographic and vascular patterns are contemporaneously present in a thyroid nodule. PMID- 11765345 TI - [Follicular neoplasm of the thyroid: usefulness of extemporaneous histologic study of frozen sections]. AB - PURPOSE: The role of frozen section (FS) in determining thyroidectomy extent in patients with follicular neoplasms is debated. The Authors consider FS usefulness through experience retrospective review. MATERIAL AND METHODS: From January 1980 to June 1999, 1252 Fine Needle Aspirations (FNA) were performed in patients with thyroid nodules. Out of these, 155 (12.4%) resulted follicular neoplasms. All these patients were operated on: 54 had total thyroidectomy because of both lobes disease and 101 had emithyroidectomy with FS. FS results were compared to definitive histological examination. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of frozen section have been estimated. RESULTS: Out of 155 follicular neoplasms, 15 resulted malignant at definitive histological examination: 6 were diagnosed by FS. All 6 patients had a total thyroidectomy during the same operation. Of the rimanenti 9, 6 had a second operation for radicalization within 2-3 days. FS sensitivity was 42.9%, specificity 100%, accuracy 92.0%, PPV 100% and NPV 8.5%. DISCUSSION: Some Authors consider FS useful because it allows to radicalize the operation immediately, in case of positivity for malignancy. Even if only few patients, the possibility to solve the problem in a one-step procedure is a great advantage. Other Authors consider FS useless because to diagnose a poor number malignant neoplasms, a lot of intra-operative examination have to be done. Costs are higher than benefits. CONCLUSIONS: The Authors believe that both attitudes are correct and the decision of using or not FS cannot be standardized. PMID- 11765347 TI - Hyperthyroidism with concurrent thyroid cancer. AB - The occurrence of thyroid malignancy is considered a rare event in hyperthyroid patients. With the aim of assessing the clinical relevance of this association, we have analyzed the incidence of thyroid cancer in hyperthyroid patients treated by surgery. The incidence of thyroid cancer was retrospectively evaluated in 202 hyperthyroid patients who underwent thyroidectomy during a twenty-year period. A thyroid cancer was diagnosed in 12 cases (5.9 per cent). Histologic examination revealed the presence of papillary carcinoma in 9 cases, follicular carcinoma in 1 case and Hurthle cell carcinoma in 2 cases. The association between thyroid cancer and hyperthyroidism was more frequent in toxic adenomas (17.8 per cent) than in toxic diffuse (5.3 per cent) or multinodular goiters (1.7 per cent). In 8 patients they presented as an occult carcinoma (maximum diameter below 1 cm), but unfavourable histologic features, such as local invasiveness and multifocality, were found in 5 of them. Follow-up data indicate that all 12 patients are currently alive and apparently free of disease. Hyperthyroid patients, particularly those affected by toxic adenomas, should be carefully evaluated to exclude the presence of concurrent malignancy. A special attention should be made moreover to the presence of "occult" lesions that, in our study was characterized in a higher proportion (62.5 per cent) of cases, by unfavourable histologic features. PMID- 11765346 TI - [Clinical role of the cytologic study of thyroid nodules]. AB - Indication to surgical treatment for thyroid nodules still represents a relevant clinical dilemma. With this regard, on a consecutive series of 434 thyroidectomies carried out in the last 3 years, the role of Fine Needle Aspiration Biopsy (FNAB) on 139 cases has been statistically evaluated. All cytologic diagnoses have been classified in three subsets: malignant [group 1]; suspect (follicular or Hurtle cell proliferation) [group 2]; benign [group 3]. Our data confirm previous observations about the high specificity of FNAB in case of diagnosis of malignancy (97.6%). On the other hand 51.6% of our cases are included in group 2; only 31.9% of these cases have shown a postoperative diagnosis of malignancy, following a suspect at FNAB. In this study, the sensibility of FNAB has been calculated including among positive results the cytologic diagnoses of group 1 + group 2: the resulting figure of 87.3% weighs the impact of FNAB on our surgical decision process. FNAB plays a crucial role in the management of nodular diseases of the thyroid, even if its overall value is limited by the burden of "suspect" cytologic diagnoses. In our hands, the integration of FNAB results with all relevant clinical data has undoubtedly contributed to increase the portion of thyroidectomies carried out for cancer, from 12.8% of our historical series to 23.2% of the last 3 years. PMID- 11765348 TI - [Role of anatomic variations and methods of hepatic artery reconstruction in the incidence of thrombosis following liver transplantation]. AB - AIM: The aim of this study was to investigate the incidence of anatomic variations of hepatic artery (HA) in order to evaluate if anatomical anomalies may be associated with an increased incidence of hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT). Moreover, we focused on arterial reconstructive technique associated with a low incidence of HAT. METHODS: We reported a consecutive series of 687 OLT in 601 patients (1986-1999). Hepatic arterial reconstruction was variable and dependent upon donor and recipient anatomy, even if arterial anastomosis was mainly of two types: the end-to-end anastomosis (EEA), used in 340/687 OLT (49.4%) and the branch patch anastomosis (BPA), performed in 347/687 OLT (50.5%). Interrupted sutures of 7/0 polypropylene always were used. RESULTS: The diagnosis of HAT was made in 17/687 patients (2.47%). Anomalous hepatic arteries were found in 5/17 cases (29.4%). In the EEA group HAT occurred in 12/340 patients (3.53%), whereas in the BPA group HAT was diagnosed in 5/347 cases (1.44%) (p = 0.078). DISCUSSION: Anatomic variations of HA, most frequently observed, were the left hepatic artery originating from the left gastric artery (9.7-18%) and the right hepatic artery originating from the superior mesenteric artery (7.5-18%). There was no increased incidence of HA complications in the presence of HA anomalies in the donor. Moreover, the existence of an anomaly in the recipient HA was not important if it had appropriate size anf flow. CONCLUSIONS: In our series, the branch patch technique, using the hepatic-gastroduodenal bifurcation, was our current preferred method of arterial anastomosis, with a HAT-rate of 1.44%. PMID- 11765349 TI - [Bacterial endocarditis. Unusual complications of acute diverticulitis]. AB - BACKGROUND: Colon diverticular disease represents an affection with high prevalence in the western countries. It appears particularly insidious in the elderly population for the presence of concomitant illnesses. CLINICAL CASE: A patient (> 80 years old) is submitted to surgical intervention in emergency sec. Hartman for acute diverticulitis and pelvic abscess. The post-operating time has been complicated for the arising of a fever resistant to the common antibiotic therapy, in absence of abdominal and respiratory objectivity. An accurate clinical examination has set the suspect of bacterial endocarditis, confirmed to the echocardiographic examination. DISCUSSION: The acute complicated diverticulitis therapy variates in according to the clinical presentation, the complications and the experience of the different Authors. A first conservative approach foresees the Total Parenteral Nutrition (TPN) and the wide spectrum antibiotic therapy and the eventual percutaneous drainage. The surgical treatment, realized with "open" or laparoscopic method, foresees the resection of the sick intestinal tract and the packing of a temporary preternatural anus. However, some Authors prefer an intestinal anastomosis performed in single time with the resection. Among all the complications, the most frequent are those affecting the respiratory and cardiovascular apparatus, as well as the sepsis. The bacterial endocarditis is not signalled in most recent international Literature. CONCLUSION: The bacterial endocarditis must be suspected in case of common antibiotic therapy resistant fever, with negative abdominal and pulmonary objectivity, arising after a septic surgical intervention. PMID- 11765350 TI - [Clinical significance of a carcinogenesis model of colorectal carcinoma]. AB - OBJECTIVE: Carcinoma of the rectal colon begins as a small neoplastic polyp which gradually increases in size and, after passing through various degrees of dysplasia, develops into an overtly malignant carcinoma. Clinical experience suggests that patients may be divided into subgroups based on the aggressivity of the tumour. The genetic mutations associated with colorectal cancer have been studied and it is known that the genes primarily responsible for biological changes in the tumour cell, in the early stages, are APC, hMSH2, k-ras2 and, in particular, p53. Indeed, the mutation at the level of gene p53 has been recognized as the most common mutation in tumour cells. The aim of this study was investigate the role of p53 and CD34 in colorectal cancer. METHODS: We studied p53 positivity using immunohistological methods and compared our results with the site, stage (using the TNM system) and histological grade of the tumour. We evaluated CD34 positivity using the same methods in order to detect and quantity the presence of angiogenesis in colorectal cancer. RESULT: P53 was found to be markedly raised in the T3 stage of colorectal cancer, while its expression was decreased in stage T2 and stage T1 carcinomas and it was not detectable in adenomas. These results suggest a close correlation between the tumour stage and the expression of p53. An analogous correlation was found between CD34 expression and angiogenesis. CONCLUSION: The overexpression of p53 in epithelial cells and raised angiogenesis (as reflected in CD34 levels) in stromal cells could represent useful prognostic factors in the management of colorectal cancer. PMID- 11765351 TI - [Anal carcinoma]. AB - The authors, want to demonstrate the operation of abdominal perianal rectum amputation, and it is considered absolute, even 80 years, in the treatment of the anal neoplasia, it is superseded by alternative methods represented by protocols radio-chemo-therapeutic associated or less to the surgery treatment. They make then a retrospective valuation since 1963 till our days on 54 patients. In the 6 patients (stadium I-II) treated after 1982 with protocols of freemall, it is was obtained disappearance of the neoplasia about 50% the cases. On overcoming of the results there was in a second group of 8 patients (1987) treated always with protocol of Greenall, in 5 of these (62.5%) could observe absence of remaining of disease. In the third group (1993) on 8 patients treated with therapy fixed radio chemo, it was registered the absence of the residual of illness in 6 patients(75.5%). Finally, from the analysis of patients observed in the last seven years, 5 of which suffered by Ca squamous in different evolutive stadium (one I stadium, three II stadium and one stadium III-B), the stadium I and II were treated with the protocol radio-chemotherapeutic obtaining total remission of the disease in the 100% of the cases. In the follow-up of 45 patients, 12 of whose were treated with the therapy combined radio-chemo and of these 10 were valuable for survival to 5 years which was about 70% superior to patients treated with only surgery therapy. PMID- 11765352 TI - [Hemorrhoids: epidemiology and correlation with chronic constipation]. AB - Following a review of international literature, AA report main results and refer their opinion about the correlation of hemorrhoidal disease with constipation, considering some variants as well as age, sex, breed, social-economic condition and geographic distribution in USA, England and Wales. Epidemiologically ten millions of people, in USA, are affected by hemorrhoidal disease; the incidence rate is 4.4% with an age distribution that shows a prevalence between 45-65 years old subject while constipation has an exponential increase with aging. Hemorrhoidal disease is significantly influenced by sex and geographic distribution that is in white breed more than in black, in social high class and in men more than women. In black breed constipation and hemorrhoidal disease present especially in lower social classes. Based on these results hemorrhoidal disease shows on epidemiological pattern that differ from constipation's one. Many questions are still present about correlations between hemorrhoidal disease and chronic constipation regarding etiopathogenesis. Only future case-control studies will solve the problem. PMID- 11765353 TI - Parathyroid cyst, a case report and review of the literature. AB - Parathyroid cysts are rare, representing 1% of all neck swellings. A correct preoperative diagnosis is rarely formulated, especially because of the non specific clinical and ultrasonographic findings; for this reason, patients are often submitted to surgery for thyroid nodules. In the present report we describe a case where the preoperative diagnosis was correctly formulated following the aspiration and PTH assay of clear, colorless, watery fluid from the cyst. While cyst aspiration is considered the elective treatment for these lesions, recurrences being uncommon, surgery was indicated in the present case because of two recurrences after aspiration and the onset of compressive symptoms. Cystic masses of the neck should be accurately diagnosed to recognize their true nature and to allow their correct and non-invasive treatment: surgery is indicated only when recurrences and symptoms are present. Indications for aspiration of all solitary cysts of the neck should be considered to correctly identify their nature. PMID- 11765354 TI - [Hemoperitoneum secondary to aneurysm of the pancreatico-duodenal artery: report of a clinical case]. AB - Pancreaticoduodenal artery (PD A) aneurysms are rare, with a reported incidence of 2% among all splanchnic artery aneurysms. Most of these lesions are undetectable until symptoms of rupture occur. In similar cases (65%), PDA rupture is usually associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity or gastrointestinal tract. Clinical picture without rupture also has been reported (35%) and is often associated with atypic abdominal signs and symptoms or diagnosed incidentally on radiology studies. The Authors report a case of octogenarian patient with ruptured PDA aneurysm and bleeding into the retroperitoneal space presenting with stable clinical condition. Surgical treatment was performed successfully after radiological diagnosis of retroperitoneal haematoma with good outcome. Patients presenting catastrophic clinical condition need rapid resuscitation and emergency laparotomy: control of the bleeding site may be successful and aetiologycal diagnosis delayed after perioperative angiography. Further laparotomy is mandatory for a definitive treatment such as PDA obliteration or resection. An alternative therapy is the transcatheter embolization. In patients with relatively stable condition, radiological study is stressed. Anyway, the aneurysm should be obliterated whenever possible to avoid rebleeding or local complications such as erosion of the neighboring structure. In conclusion, an appropriate and early treatment lead to a good outcomes. PMID- 11765355 TI - [Endoscopic treatment of a calculous choledochocele. Report of a case]. AB - OBJECTIVE: The authors report their experience about the treatment of choledochocele. DESIGN: Case report and 6-months follow up. SETTING: Operative Unit of General and Thoracic Surgery, Department of Surgical and Anatomical Disciplines. Policlinico, University of Palermo. INTERVENTIONS: ERCP + ES with complete resolution of pathology. RESULT: Complete resolution of symptoms; 6 months follow up negative. CONCLUSIONS: ERCP is choice treatment of choledochocele, only in well experienced teams. PMID- 11765356 TI - [Fournier syndrome: multidisciplinary approach]. AB - Fournier's gangrene, a form of necrotizing fasciitis, is an uncommon, fulminant, rapidly progressing subcutaneous infection of the scrotum and genito-perineal region, and may occur in all age groups. Most cases involve a mixed synergistic infection of aerobic and anaerobic bacteria, and occur as a result of one of this mechanisms: local trauma, extension from a perineal, periurethral or ischiorectal infection. It is associated with a high mortality rate. Predisposing factors included diabetes mellitus, steroids or chemotherapy, alcohol abuse, malignancy and radiation therapy. This disease requires prompt treatment: early diagnosis, antibiotic therapy, nutritional support, immediate extensive surgical debridement and hyperbaric oxygen therapy. The use of etherologue serum is a valuable adjunct in the therapy of Fournier's gangrene. We report a case of Fournier's syndrome treated with etherologue serum immuno-therapy, together with the conventional multidisciplinary approach. The postoperative course was uneventful and the patient was discharged on day 50 post intervention in good general conditions. The 3 years follow-up showed no recurrence of the disease. In conclusion we remark that the survival can be improved in patients with Fournier's gangrene by multidisciplinary approach. PMID- 11765357 TI - [Scrotal angiomyofibroblastoma. Report of a case]. AB - OBJECTIVE: The authors report their experience about the treatment of a rare case of scrotal angiomyofibroblastoma (AMF). DESIGN: Report of 1 cases; evaluation of effectiveness of surgical treatment. SETTING: Operative Unit of General and Thoracic Surgery, Department of Surgical, Anatomical and Oncological Disciplines. Policlinico, University of Palermo. INTERVENTIONS: The patient was submitted to curative and radical surgery. RESULTS: Resolution of the pathology. Follow up (6 months) negative. CONCLUSIONS: The AMF's treatment is surgical and localized. Is important the complete preoperative evaluation. PMID- 11765358 TI - Cash flow woes. CMS outpatient payment changes under fire. PMID- 11765359 TI - Sizing up the top health insurers. Big-time buyer WellPoint, smart seller Aetna a study in contrasts. PMID- 11765360 TI - HMOs thriving but still cautious. PMID- 11765361 TI - The leverage line. AMA's online complaint site aims to aid case for doc bargaining with HMOs. PMID- 11765362 TI - Forum good for CT's image. New technology hogs spotlight at RSNA event. PMID- 11765363 TI - Joining forces. Manufacturer-backed GHX brings distributor-backed HealthNexis into fold. PMID- 11765364 TI - New sheriff in town. Health insurers take antitrust enforcement matters into own hands with litany of lawsuits. PMID- 11765365 TI - HMOs aren't shedding tiers. First it was drug pricing; now health plans are turning to 'select' providers. PMID- 11765366 TI - Safeguarding the supply chain. Philadelphia hospital learns how easily purchasing practices can go awry. PMID- 11765367 TI - Turning creditors into owners. Nursing home chains emerge from bankruptcy with lenders in charge. PMID- 11765368 TI - Web survey. October results: are we prepared? PMID- 11765369 TI - A deal that's hard to refuse. Physicians use clout to win joint ventures with hospitals despite fiscal perils. AB - Just as many hospitals rid themselves of unprofitable medical practices, a risky new strategy to win physician loyalty is gaining popularity: hospital-physician joint ventures. Some analysts say the deals could backfire, as the dangers for hospital balance sheets outweigh the benefits. PMID- 11765370 TI - Ascension ventures forth. Catholic system in unlikely land of venture capital. PMID- 11765371 TI - Just another hand out. Effort to ease cuts in Medicare doc fee schedule faces tough competition. PMID- 11765372 TI - Cashing in on fear. PMID- 11765373 TI - The first clone. PMID- 11765374 TI - Pediatric hematopoietic stem cell transplantation. AB - The successful use of allogeneic HSCT for children with malignant and nonmalignant diseases continues to be limited by the development of acute and chronic GVHD, infectious complications, delayed recovery of the immune system, acute and long-term toxicity, and relapse of disease. Significant advances have been made, particularly in the ability to identify suitable sources of HSC. Future advances will depend on a better understanding of the biology of HSC sources, GVHD, immune reconstitution, and common complications. Improved therapies are dependent on participation of children in well-designed, translational and clinical transplant studies. PMID- 11765375 TI - Nonmyeloablative transplantation in children. Current status and future prospects. AB - Over the last few years a variety of conditioning regimens have been developed that allow allogeneic hematopoietic stem cell engraftment with significantly decreased transplant related-toxicity. While these reduced-intensity regimens have offered hope for patients with malignancies formerly not eligible for myeloablative transplantation due to excessive morbidity (older patients and patients with significant organ toxicity), the role of nonmyeloablative hematopoietic cell transplantation (NM-HCT) in children is unclear. A review of the available literature for pediatric and adult studies shows several malignancies in which approaches designed to limit long-term complications in children may be appropriate. In addition, NM-HCT may offer a safer approach for children with inherited disorders curable by marrow transplantation, such as immunodeficiencies, hemoglobinopathies, or storage diseases. Finally, use of this approach to establish partial donor chimerism may provide an immunologic platform that will allow specific cellular therapies, targeted gene therapy, or immunologic tolerance in solid organ transplantation. PMID- 11765376 TI - Antiangiogenesis therapy. Current and future agents. AB - Approaches to cancer therapy for most tumors in adults and children have changed little in 50 years: surgery, radiation, and chemotherapy are standard for many solid tumors. When the concept of angiogenesis in cancer biology was introduced in the 1970s, there was little recognition of the therapeutic potential of attacking a tumor's blood supply. Advances in understanding the molecular processes that regulate tumor blood supply and novel agents that can interfere with them have generated a great deal of scientific interest and excitement. This article reviews the current understanding of angiogenesis and its role in cancer then discusses new therapeutic options in animals and humans, with a focus on pediatric tumors and the potential for treating them. PMID- 11765377 TI - Monoclonal antibody-based therapy of neuroblastoma. AB - The curative potential of mAbs in the treatment of patients with metastatic neuroblastoma is increasingly evident. The idiotype network appears to represent one component of a complex mechanism for success with mAb-based immunotherapy. Ongoing strategies to modify or reconstruct mAbs, to engage them with cytokines, or to unite them with T cells open new avenues for harnessing the unique forces of the immune system against some of the most deadly pediatric cancers. PMID- 11765378 TI - Retinoid therapy of childhood cancer. AB - In vitro studies that showed RA could cause growth arrest and differentiation of myelogenous leukemia and neuroblastoma led to clinical trials of retinoids in APL and neuroblastoma that increased survival for both of those diseases. In the case of APL, ATRA has been the drug of choice, and preclinical and clinical data support direct combinations of ATRA with cytotoxic chemotherapy. For neuroblastoma, a phase I study defined a dose of 13-cis-RA, which was tolerable in patients after myeloablative therapy, and a phase III trial that showed postconsolidation therapy with 13-cis-RA improved EFS for patients with high-risk neuroblastoma. Preclinical studies in neuroblastoma indicate that ATRA or 13-cis RA can antagonize cytotoxic chemotherapy and radiation, so use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. A limitation on the antitumor benefit of ATRA in APL is the marked decrease in drug levels that occurs during therapy as a result of induction of drug metabolism, resulting in a shorter drug half-life and decreased plasma levels. Although early studies sought to overcome the pharmacologic limitations of ATRA therapy in APL, the demonstration that ATO is active against APL in RA-refractory patients has led to a focus on studies employing ATO. Use of 13-cis-RA in neuroblastoma has avoided the decreased plasma levels seen with ATRA. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13 cis-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase I trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. PMID- 11765379 TI - Gene expression profiling. Methods and clinical applications in oncology. AB - The advent of microarray technology undoubtedly will have great impact on the medical field during the next decade. This article discusses different genomic technologies, statistical methods for data analysis, and clinical applications of microarrays. Emphasis is devoted to integration of microarrays into the field of pediatric oncology. PMID- 11765380 TI - Pathways of apoptosis and the modulation of cell death in cancer. AB - Although cell death once was viewed exclusively as the disordered, chaotic outcome of metabolic catastrophe, apoptosis now is recognized as a highly ordered, evolutionarily conserved, and genetically selected program that is essential for normal development. The death receptor pathway of apoptosis, cytotoxic T cells, prolife survival signals, Bcl-2 family of regulators, p53 and regulated cell death in cancer, and oncogenes are reviewed. Future prospects in this arena also are discussed. PMID- 11765381 TI - The failure of a controlled trial to improve depression care: a qualitative study. AB - BACKGROUND: The DIAMOND Project (Depression Is A MANageable Disorder), a nonrandomized controlled effectiveness trial, was intended to improve the long term management of depression in primary care medical clinics. The project tested whether a quality improvement (QI) intervention could implement a systems approach-so that there would be more reliable and effective monitoring of patients with depression, leading to better outcomes. THE QUALITATIVE STUDY: A study was conducted in 1998-2000 to determine why a quality improvement intervention to improve depression care did not have a significant impact. Data consisted of detailed notes from observations of 12 project-related events (for example, team meetings and presentations) and open-ended interviews with a purposive sampling of 17 key informants. Thematic analytic methods were used to identify themes in the contextual data. PRINCIPAL FINDINGS: Overall, the project implementation was very limited. Five themes emerged: (1) The project received only lukewarm support from clinic and medical group leadership. (2) Clinicians did not perceive an urgent need for the new care system, and therefore there was a lack of impetus to change. (3) The improvement initiative was perceived as too complex by the physicians. (4) There was an inherent disconnect between the commitment of the improvement team and the unresponsiveness of most other clinic staff. (5) The doctor focus in clinic culture created a catch-22 dilemma-the involvement and noninvolvement of physicians were both problematic. CONCLUSION: Problems in both predisposing and enabling factors accounted for the ultimate failure of the DIAMOND quality improvement effort. PMID- 11765382 TI - Implementing guidelines for interdisciplinary care of low back pain: a critical role for pre-appointment management of specialty referrals. AB - BACKGROUND: Improving health care will require more effective guideline implementation and redesign of delivery processes and systems. Patient referral for specialty care is a key component of health system function that needs to be improved. Low back pain care is a widely documented example of the need for improvement. An interdisciplinary systemwide back pain program was developed using process improvement methods. Proactively managing referrals for specialty care-a departure from traditional referral processes-played a critical role in implementing the program. METHODS: Program components included guidelines for care, defined provider roles, uniform service coding, provider and patient education, pre-appointment specialty referral management, and monitoring of management processes. To evaluate program performance, system back pain visits were compared before, during, and after implementation of referral management. A case series study was performed on 581 consecutive patients with low back pain or lumbar radiculopathy referred for consultative spine care between April 1998 and March 1999. RESULTS: A shift of care was accomplished for acute back pain from spine orthopedists to primary physicians and for chronic back pain from spine orthopedists to medical specialists. More than 95% of initial assignments were accurate. Seventy-six percent of surveyed chronic back pain patients improved, and 90% were highly satisfied with the referral management process. This program has saved an estimated $400,000 per year in manpower cost and has reduced specialty service billings by 20%. DISCUSSION: Pre-appointment referral management offers an approach for improving guideline implementation, access to specialty services, and the effectiveness of care for complex health problems. It deserves broader study and adoption. PMID- 11765383 TI - Collaboration to implement smoking cessation guidelines during the childbirth continuum. AB - BACKGROUND: Smoking during pregnancy has been linked with such negative outcomes as increased risk for spontaneous abortions, low birth weight, and perinatal and neonatal mortality. In spring 1998 three leading health care systems in San Diego initiated the Trilateral Partnership ("the Partnership"), whose mission is to improve the health and well-being of children. The Partnership chose tobacco control in pregnant women and their families as its first initiative. PROGRAM COMPONENTS-YEAR ONE (1999): Three interventions were developed: intervention by the prenatal care provider, initiation of a referral process to telephone counseling for pregnant women, and intervention for women reporting spontaneously quitting smoking. To date, 83% of the more-than 20,000 women who have been seen in prenatal screening in 28 months counted themselves as nonsmokers. Eleven percent of the women reported they independently stopped smoking once they learned they were pregnant. Six percent reported that they were still smoking. Twenty-three percent of the women reported living in a household with other smokers. PROGRAM COMPONENTS-YEAR TWO (2000): Activity focused on continuing the previous components, hospital intervention for all new mothers at the time of delivery, pediatric intervention at the newborn's visits at 2 and 6 months of age, and development and refinement of a telephone protocol for new parents. ELEMENTS OF SUCCESS: The noncontroversial topic of encouraging smoking cessation during pregnancy was one that enhanced immediate buy-in by most individuals contacted to support and engage in the program. Strong commitment and financial support from three health care systems opened doors for the Smoke-Free Families staff and increased the program's visibility in the community. PMID- 11765384 TI - Methods for evaluating the provision of well child care. AB - BACKGROUND: Well child visits are important for reducing the incidence of avoidable illness and disease. The Omnibus Reconciliation Act of 1989 (OBRA '89) set goals for well child or Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) visits. Many health plans are evaluated in terms of the number of well child visits provided, yet the method used for collecting the data influences the indicator results and conclusions drawn from them. METHODS: In a retrospective cohort design, medical record review and administrative data were compared as methods for ascertaining the number of well child visits received by Iowa Medicaid-eligible children for the period from July 1, 1997 through December 31, 1998. Compliance with the American Academy of Pediatrics' "Recommendations for Preventive Pediatric Health Care" periodicity guidelines was assessed. RESULTS: Using administrative data, 29.6% (n = 1,489) of children received a well child visit. If medical record review was used, 39.6% (n = 1,003) of children had a visit. The concordance between the rates was quite low (kappa = 0.30). Medical record review supported that an EPSDT visit was provided for only 68% of the children who had a claim or encounter billed as providing well child care (n = 441). DISCUSSION: Administrative data may underestimate the performance of EPSDT visits in comparison to medical record review. In addition, having a claim for an EPSDT visit did not necessarily mean the child received the basic components of a well child exam. The methodology for performance indicators used to evaluate health plans should be carefully validated. PMID- 11765385 TI - Using performance measures to identify plans of action to improve care. AB - BACKGROUND: Health care organizations dedicate enormous time and resources collecting data to measure the performance of physicians, hospitals, and other medical facilities. These measures may reflect outcomes, processes of care, patient perceptions of the quality of care, and resource utilization and cost. However, less thought is given to how the performance data should be used to improve care. The data must be translated into clinically relevant terms that assess the decisions of the clinical staff and the functioning of the systems that support the delivery of care. The processes of care are identified through record review, analysis of the system of care delivery, and patient interview, and are then further assessed to determine the underlying causes. EXAMPLES: Examples, drawn from case studies, are provided to illustrate how to identify and address components of care requiring improvement. DISCUSSION: Physician behavior is an important component of care in all performance measures. Modification of some patterns of behavior, including those of nursing and other support staff, may be needed to reduce some types of error. For this reason it is important to involve physicians in the process of discovering root causes. When the root cause involves the medical care system, an interdisciplinary approach will be needed. This may involve administrators, nurses, pharmacists, home care and discharge planners, and office personnel. One recommended approach to QI is to identify system errors and then design changes in the system to reduce that type of error. CONCLUSION: Performance measures must be translated into the components(s) of care that are implicated in the measure. Once this component has been identified as the reason behind the suboptimal measure, its root cause should be used to structure the most effective intervention. PMID- 11765386 TI - Unmet need for reproductive health in India. AB - Using data from the National Family Health Survey of 1992-93 and the individual reproductive histories of a cross-section of 70 women from rural Tamil Nadu, this paper exposes the limited extent to which women in India have been able to achieve their reproductive intentions and the failure of health services to meet their considerable reproductive health needs. Of the 70 women, 69 had been unable to achieve their reproductive intentions, not only non-users of contraception but also ever-users, and all 69 had an unmet need for reproductive health services. Sterilisation is often the first and only method of contraception taken up and only after a series of wanted, mistimed and unwanted pregnancies, miscarriages, induced abortions and neonatal and infant deaths. Women who wanted to have more children than they were able to were also found. Given the paradigm policy shift in India from promoting fertility reduction only to meeting women's reproductive and sexual health needs, a more useful concept for measuring 'unmet need' for services in programme planning is required, one such as the HARI index, that would capture the extent to which individual women are achieving their reproductive intentions in good health. Without this, the same problems will only recur in younger women. PMID- 11765387 TI - Including expectant fathers in antenatal education programmes in Istanbul, Turkey. AB - In this article we present the results of three studies investigating methods for including men in antenatal education in Istanbul, Turkey. Participants were first time expectant parents living in low and middle-income areas. After a formative study on the roles of various family members in health during the period surrounding a first birth, an antenatal-clinic-based education programme for women and for couples was carried out as a randomised, controlled study. Based on the results, separate community-based antenatal education programmes for expectant mothers and expectant fathers were tested. There was demand among many pregnant women and some of their husbands for including expectant fathers in antenatal education. In the short term, these programmes seemed to have positive effects on women and men's reproductive health knowledge, attitudes and behaviours. In the clinic-based programme the positive effects of including men were mainly in the area of post-partum family planning, while in the community based programme positive effects among men were also seen in the areas of infant health, infant feeding and spousal communication and support. Free antenatal education should be made available to all expectant mothers and when possible, men should be included, either together with their wives or in a culture such as that of Turkey, in separate groups. PMID- 11765389 TI - Statement on attacks in the USA. Women Living Under Muslim Laws, International Solidarity Network, 21 September 2001. PMID- 11765390 TI - Community-based survey on female genital excision in Faranah District, Guinea. AB - This paper reports on a community-based study in 1999 of the beliefs and practices of people in Faranah District, Guinea regarding female genital excision (FGE). Semi-structured individual interviews and focus group discussions were carried out with women of reproductive age, older women, married men, community and religious leaders, traditional practitioners and health workers. The study found that FGE was being carried out on girls aged 6-14, mostly using a traditional knife and involving total excision of the clitoris and partial removal of the external genitals, in conjunction with instruction on how young women should behave when they are married. The practice is illegal under national laws but few people were aware of this. There was a tendency towards taking girls for medical care to avoid complications, and some people suggested that FGE should be done by medical professionals, but this was a minority. More than 60 per cent of respondents thought FGE was harmful to health and supported its abolition. Many more men than women took this view; women felt under pressure to maintain the tradition. To stop FGE, local organisations need to support a process of change within the community, including awareness-raising about the law and the negative health effects of FGE, promoting alternative ceremonies, educating practitioners and supporting education and improvements in the status of women. PMID- 11765388 TI - Lives renewed: the emergence of a breast cancer survivor movement in Ukraine. AB - Breast cancer is the leading cause of cancer deaths among women in Ukraine. In addition to the physical toll that breast cancer takes, the psychological and emotional needs of women diagnosed with the disease are great but rarely addressed. Since 1997, with initial technical assistance from the Program for Appropriate Technology in Health (PATH), a nascent breast cancer survivor movement has emerged in Ukraine, which aims to challenge societal stigmatization of the disease. As of mid-2001, survivor groups have been formed in 15 cities, representing 12 of the country's 25 provinces, and groups in eight cities have begun implementing Peer Support Volunteer programmes through which survivors provide information and emotional support to newly diagnosed women in hospital. Survivors also are playing an important role in raising public awareness about the disease through public events, outreach activities and the media. The groups have also forged alliances with key medical professionals specialising in cancer care, both to educate them about the potential role that survivors' groups can play in assisting patients, as well as to enlist their active support for these efforts. Solidifying the groups' organisational structures and strengthening their management and fundraising skills have been vital to success. PMID- 11765391 TI - Male circumcision as an HIV control strategy: not a 'natural condom'. AB - Recent epidemiological studies have shown fairly convincingly that in high-risk populations in sub-Saharan Africa, male circumcision is associated with a reduced risk of HIV infection. Following a consultation at the XIII International AIDS Conference in July 2000 in Durban, there was growing interest in such an intervention. This paper explores what is known about male circumcision, the risks associated with it, its relationship with sexual health, including HIV and other sexually transmitted infections (STIs), and the potential problems with implementing circumcision as an intervention internationally, particularly in traditionally non-circumcising communities and those where access to medical facilities is limited. Proponents of male circumcision as an HIV prevention strategy are convinced and convincing, but circumcision is a surgical procedure with associated risks and has strong religious and cultural significance for many groups. Hence, there are ethical and practical barriers to implementing it as a public health intervention. The evidence suggests that circumcision may reduce the risk of infection, but circumcision does not appear to have any impact on transmission rates from HIV positive men to their partners. Until we know why and how circumcision is protective, exactly what the relationship is between circumcision status and other STIs, and whether the effect seen in high-risk populations is generalisable to other groups, the wisest course is to recommend risk reduction strategies of proven efficacy, such as condom use. PMID- 11765392 TI - Impact of chemical warfare with agent orange on women's reproductive lives in Vietnam: a pilot study. AB - During the American war in Vietnam, huge quantities of the highly toxic herbicide dioxin ('Agent Orange'), were sprayed over large areas of central and south Vietnam. In addition to polluting the environment and causing cancers and other diseases in those directly exposed to it, dioxin has caused high rates of pregnancy loss, congenital birth defects and other health problems in their children. This paper reports the findings of a pilot study in the year 2000 among 30 Vietnamese women whose husbands and/or who themselves were exposed to Agent Orange. The aim was to develop research in order to explore the impact of chemical warfare on people's lives. Using the reproductive lifeline and semi structured interviews, information was gathered on both partners' periods of exposure to Agent Orange, pregnancy outcomes, perceived health problems of children and experiences of living with handicapped children. The women had had a high number of miscarriages and premature births. About two-thirds of their children had congenital malformations or developed disabilities within the first years of life. Most of the families were poor, aggravated by impaired health in the men, the burden of caring for disabled children, and feelings of guilt and inferiority. The plight of 'Agent Orange families' is special and should be placed in its historical and political context. PMID- 11765393 TI - Alternative study designs for research on women's gynaecological morbidity in developing countries. AB - Although community-based studies are considered to be the 'gold standard' for research on gynaecological morbidity among women, there is growing appreciation of the significant challenges to successfully undertaking such studies in developing countries. In this review, the constraints to undertaking community based studies are discussed and alternative study designs are evaluated. Our review suggests that these alternative designs have both limitations as well as strengths compared to community-based designs. An important limitation concerns possible selection bias in the populations studied and the extent to which findings can be generalized to the broader population. Important advantages include higher feasibility, lower respondent refusal rates especially for medical procedures, lower costs, and potentially a more direct link between research and utilization. We conclude that the alternative study designs considered provide researchers with an expanded array of tools for investigating the issue of women's gynaecological morbidity in developing countries. PMID- 11765394 TI - Facilitating access to essential health commodities through south-to-south collaboration: Kochi Declaration. Partners in Population and Development, 14 June 2001. PMID- 11765395 TI - Images of the body and the reproductive system among men and women living in Shantytowns in Porto Alegre, Brazil. AB - This paper presents the results of anthropological research on graphic and verbal images of the reproductive system carried out among 99 women and 103 men living in four shantytowns in Porto Alegre, Brazil. Interviewers were instructed to ask for the drawings in the course of interviews lasting 12-20 hours. Some 55 drawings of the female reproductive system by men and 99 by women were produced and are analysed here together with information from the interviews and observational data. The majority of the men's drawings of women's reproductive system tended to include 'external' body parts only, in contrast with the 'hidden' nature of the internal body parts, which were commonly depicted by the women. Women have been more exposed to the health system than men and the majority made basic biomedical types of drawings. However, their verbal representations were sometimes informed by other notions and values and their physical experience of their bodies. Lack of contact with the health system does not fully account for the men's apparent lack of knowledge about the reproductive body. Rather, biomedical knowledge was simply not a point of reference for the men's understandings of the body. The majority of drawings made by men of the female reproductive body portrayed the primacy of sexuality in their view of the reproductive system. PMID- 11765396 TI - Homosexuality and adoption in Brazil. AB - Western societies are undergoing legal and policy changes in relation to laws governing the family, marital status, sexual orientation and the welfare of children, including in Brazil where, in the 1990s, the rights of homosexuals were incorporated into ongoing debates about what constitutes a family. This paper discusses the issue of adoption of children by homosexual men in Brazil, using information from court records from 1995-2000 in Rio de Janeiro, and from interviews with two judges, five psychologists and four social workers who evaluate those wishing to adopt. It uses the case records of one man's application to adopt, in which homosexuality became a central issue. Both the construction of masculinity in relation to parenting and concepts of the family were the parameters upon which the decision to allow him to adopt or not depended. Because the legislation does not specify what the sexual orientation of would-be adoptive parents should be, it is possible for single persons to adopt if they show they can be good parents. As more single people, alone or in couples, seek to adopt, it is important to clarify the criteria for judicial decisions on adoption applications. A dialogue is therefore needed on the meaning of family and whether and how it relates to sexual orientation. It is only on this basis that the courts can take a clear decision as to whether being homosexual is a relevant issue in regard to applications to adopt or not. PMID- 11765397 TI - Exploiting images of young girls in the media. Letter to the editor of the Financial Gazette, Harare, 10 August 2001. PMID- 11765398 TI - Reading between the lines: direct-to-consumer advertising of genetic testing in the USA. AB - This article critiques an advertisement in a theatre playbill by a bio-technology company for its commercial test for the BRCA1 and BRCA2 genetic mutation, which may indicate a higher risk for breast and ovarian cancer. The advertisement targets a vulnerable audience attending a play about one woman's isolated and painful death from ovarian cancer. It promotes a product with incomplete and at times incorrect information, and it misguides women by suggesting that they contact the company directly about this test, rather than encouraging them to talk to their health care providers about genetic testing and their personal risk of breast cancer. In an era in which more genetic tests will be integrated into clinical practice, we can expect an increase in direct-to-consumer marketing for such tests. This advertisement is an example of what we need to be on guard against. PMID- 11765399 TI - Addressing semen loss concerns: towards culturally appropriate HIV/AIDS interventions in Gujarat, India. AB - A situation analysis of sexual networking and sexual health in an industrial area of Gujarat, India, identified anxiety about masturbation and other semen loss concerns as major preoccupations among young men. This paper describes how the Deepak Charitable Trust addressed these concerns in their HIV prevention programme for young men aged 15 to 30. Flowcharts were used as participatory learning tools and to obtain data on the perceived consequences of masturbation, both before and after intervention activities. Research was also done on the relation between semen-related anxieties and sexual risk behaviour by DCT and two other NGOs among young men engaging in unsafe sexual behaviour. DCT advocates addressing masturbation and other semen loss concerns in all sexual health campaigns in South Asia, based on the magnitude of these concerns, their potential to confound syndromic management of STIs and their significance as an idiom of psychosocial distress. Masturbation and associated anxieties about sexual performance are seen as health issues and discussed as such by the programme. There is immediate identification among young men, whether or not they are already sexually active, and it provides an excellent entry point for sexual health and safer sex education. The community response to these efforts has been entirely positive. PMID- 11765400 TI - Images, reproductive health and the collateral damage to women of fundamentalism and war. PMID- 11765401 TI - Male circumcision and penis enhancement in Southeast Asia: matters of pain and pleasure. AB - This paper reviews some uniquely male sexual health concerns in Southeast Asia, with particular attention to Indonesia. These include various forms of male circumcision, different types of 'penis enhancement' carried out across the region and the use of dry sex by women. These practices appear to be motivated by specific notions of sexual pleasure, based on indigenous gender constructs. Although they may or may not pose a serious public health problem, as markers of misguided or exploitative gender relations they do reveal important aspects of social psychology related to sexuality and sexual health. Male circumcision provides an ideal opportunity to consider male reproductive health needs and risks in Indonesia, Malaysia and the Philippines. Practices that involve cutting the male genitals need to be addressed in ways that stress the importance of sexual relationships based on mutual respect and open communication. Penis implants and inserts and other penis augmentation devices, as well as dry sex practices, are potentially dangerous to both men and women, and of questionable value in bringing pleasure to either, and should be discouraged. PMID- 11765402 TI - Reproductive health under attack at the United Nations. PMID- 11765403 TI - Comprehensive health care for women in a public hospital in Sao Paulo, Brazil. AB - This paper describes a model of integrated reproductive health care services for women at the primary health care level, put into practice at the Perola Byington Hospital, Sao Paulo, Brazil, from 1991 to 1998. Some 2,000 women from poor social strata, whose health condition was poor, were being seen every day in the last two years of the programme, including new consultations and women with a previous attendance returning. Women were attended first by nurse-assistants, who had been trained to screen for the most frequent gynaecological problems, and then a physician. Because doctors spent less time with each patient, four times as many women could be seen. Programmes were set up for the diagnosis and treatment of gynaecological cancers, STDs, HIV/AIDS, hypertension and other degenerative disorders such as diabetes. Screening and treatment programmes for cervical and breast cancer achieved significant improvements in the stage at which a diagnosis was made, allowing more lives to be saved. This model also succeeded in decreasing the costs for these health services per woman seen. PMID- 11765404 TI - The challenges of meeting rural Bangladeshi women's needs in delivery care. AB - Despite initiatives and interventions undertaken at national and international levels, maternal health is still neglected in Bangladesh, and the maternal mortality ratio remains one of the highest in the world. In order to improve rural women's access to maternity care, in 1996 the Bangladesh Rural Advancement Committee (BRAC) instituted services for birthing women in 21 health facilities in each Thana. This paper reports on research conducted three years later, based on interviews with women who gave birth in one BRAC Health Centre (BHC) and women who gave birth at home, interviews with staff of the BHC and observation of provider-patient relations. Acceptance of delivery in a health facility by rural women is still minimal. Most women only attended the BHC due to complications, yet the BHC was unable to handle most complications and referred women to the district hospital, where they received poor quality care. Cost, fear of hospitals and the stigma of an 'abnormal' birth were also important constraints. Female paramedics who attended normal deliveries were praised for being caring, but made women deliver lying down, did not always use aseptic procedures and were too busy to give information, making birth a passive experience. Recommendations to provide comprehensive emergency obstetric care at the BHC and upgrade staff skills, introduce rural health insurance and others have already begun to be implemented. PMID- 11765405 TI - Giving birth in maternity hospitals in Benin: testimonies of women. AB - In Benin, a Francophone country in West Africa, maternity mortality has been estimated at between 473 and 990 deaths per 100,000 live births. Yet 92 per cent of women gave birth in either a public or private health centre, and almost all of them received antenatal care. This paper reports on an exploratory, qualitative study in 1995, among 19 women aged 20-40 who had recently given birth in a referral hospital, of their experiences of antenatal and emergency obstetric care, as part of a larger study on measuring the prevalence of severe maternal morbidity in the community. Thirteen of the women had had obstetric complications and 11 had had a caesarean section. Pregnancy was described as a period of great vulnerability, and feelings of insecurity and fear of death were omnipresent in the women's accounts. Their primary motivation for seeking antenatal care was the appearance of symptoms or events they perceived as abnormal. Although a minority were lucky enough to have a kind midwife, many complained about not being able to ask questions or get any explanations, being mistreated and humiliated by health personnel and described the anguish they felt in the face of medical procedures they did not understand, especially caesarean section, which they were told were necessary to save their lives. Access to emergency obstetric care is a priority in the battle against maternal mortality, but it cannot be at the expense of improvements in the quality of the interaction between women and health personnel. The inclusion of women's voices in the objectives of safe motherhood programmes is necessary to better serve women's needs. PMID- 11765406 TI - From the forest to the clinic: changing birth practice among the Katang, Lao. AB - It is the right of indigenous peoples to maintain traditional cultural practices but women's right to reproductive health may be compromised by the very beliefs and practices that define culture. Based on interviews with Katang villagers and a range of local medical practitioners, this paper describes how the Katang people of Lao are coming to terms with this dilemma in a context of development and change. Indigenous religion prohibits Katang women from giving birth in the house; traditionally they go into the forest for delivery. The birthing hut (an innovation in one village), training of six TBAs, the opening of a primary level clinic where normal births can take place and growing awareness of the need for referral to higher levels of care in case of complications are all changes that are transforming women's childbirth experience. As these changes become established, and awareness grows in the local communities of the importance of being able to access services in a timely way, the possibility of reducing maternal deaths will become a reality. PMID- 11765407 TI - [Morphofunctional characteristics of the thyroid of fetuses and newborns according to autopsy data from St. Petersburg]. AB - 121 thyroids of fetuses after 25 weeks of gestation and newborns of mothers living in St-Petersburg were investigated. The conclusions on morpho-functional state of the thyroid at late terms of intrauterine development and newborns in St Petersburg were made on the basis of macroscopical, histological, morphometrical and immunohistochemical findings. PMID- 11765408 TI - [Reactive restructuring of ureteral smooth muscle tissue during development of urinary vesico-ureteral reflux in children]. AB - By means of target cell dissociation we studied the cells of smooth muscle tissue from the wall of intact ureter in children in the course of compensatory-adaptive reactions in the vesico-ureteral reflux. Three types of ureteral myocytes differing by structural-metabolic parameters are distinguished. A comparative analysis of the intact and reactively altered ureteral smooth muscle tissue has revealed changes in the population structure manifesting with high optic density of DNA from myocytic nuclei and high activity of synthetic processes in the cytoplasm. PMID- 11765409 TI - [Morphometrical and immunohistochemical characteristics of the vascular component of the communication systems in the central and peripheral zones of breast cancer nodes before and after radiation therapy]. AB - Communicative systems are involved in morphogenesis of breast cancer. Intensive local irradiation, on the one hand, results in the death of a part of tumor cells in the central zones of breast tumor node. On the other hand, it stops local immune and, consequently, cytolytic reactions in the periarteriolar zones and inhibits these reactions in the pericapillary zones. Therefore, tumor cells in these zones survive and may proliferate. PMID- 11765410 TI - [Morphological aspects of intense preoperative hypoxyradiotherapy in combined treatment of patients with sigmoid colon carcinoma]. AB - Morphological study has confirmed the advantage of using doses of single radiation doses 5 Gy (total dose 25 Gy) and inhalation of a hypoxic gas mixture vs other methods of treatment. The study of radiation pathomorphosis showed significants devitalization of the tumor cells realized clinically with a fall in the number of postoperative recurrences and metastases. PMID- 11765411 TI - [Molecular mechanisms of regulation of cytotrophoblastic invasion in uteroplacental region]. AB - Cytotrophoblastic invasion is a unique, short-distance, tumor-like growth of specialized placental cells (symplastic complexes, cytotrophoblast) in the direction of uterine endo- and myometrium. After the primary invasion during the implantation the first (week 5-8) and the second (week 16-18) cytotrophoblast invasion waves take place which by arrosion of spiral arteries form permanent uterine-placental blood circulation. PMID- 11765412 TI - [Pathomorphological and hormonal criteria in the diagnosis of causes of spontaneous abortions]. AB - The authors think it necessary to research causes of each case of spontaneous abortion more thoroughly. Pathomorphological manifestations of chromosomal, endocrine, immune and infectious pathology of the fetal bubble and endometrium are described. These criteria are compared to then content of sex steroid hormones in the circulating blood of pregnant women. PMID- 11765413 TI - [Lung carcinoma metastasis in renal adenoma: immunohistochemical study]. AB - The phenomenon of a tumor-to-tumor metastasis is studied immunohistochemically. About 120 similar cases were published since 1902. Well vascularized and slowly growing renal tumors are typical recipients for such metastases. A case of a lung cancer metastasis verified immunohistochemically into renal adenoma is reported in a male aged 65 years. Immunophenotypical features of the primary and metastatic foci as well as renal cell adenoma are described. Diversification of lung squamous cell carcinoma and its metastasis in renal adenoma is demonstrated. PMID- 11765414 TI - [Primary esophageal melanoma ]. AB - Two cases of esophageal primary melanoma in females aged 63 and 68 years with nodular and lentiginous forms of growth are reported. The diagnosis was made intraoperatively and at autopsy, respectively. Morphogenetically, there were primary multiple non-simultaneous zones of tumor growth with the apposition growth as a form of tumor progression. Early stages of morphogenesis were characterized by atypical borderline melanocytic activity, melanoma in situ with a starting invasive growth being basic criteria for diagnosis of primary esophageal melanoma in examination of endoscopic and surgical material. PMID- 11765415 TI - [Giant petrifaction in infarction of the right ventricular posterior wall]. AB - The paper reports a lethal outcome of recurrent myocardial infarction in a male patient who in 1996 survived a massive infarction of the right ventricle posterior wall resulting in formation of a giant petrificate with a softening in the center. Connective tissue growth and cardiomyocytic atrophy was histologically revealed in the surrounding tissue. The patient died in 1999 of the infarction of the anterior wall of the left ventricle. PMID- 11765417 TI - [Functional morphology and prognosis of hormonally-active pituitary adenomas]. AB - This paper is a review of literature on the etiology, pathogenesis and morphogenesis (electron microscopy, immunocytochemistry) of pituitary adenomas (PA). Clinical manifestations of PA are considered depending on their structure. Approaches to the clinico-morphological classification of PA and factors of their prognosis are discussed. PMID- 11765416 TI - [About morphology and classification of tumor-like and malignant prostatic lesions]. AB - This review contains updated information on benign prostatic hyperplasia, basal cell hyperplasia, atypical adenomatous hyperplasia, prostatic intraepithelial neoplasia, different forms of carcinoma and rare prostatic neoplasms. The literature and the authors' clinico-morphological investigation of 687 patients are analysed. The diagnostic significance of some morphological markers (mitotic activity, the presence of crystalloids, amyloid bodies, the activity of endocrine paracrine cells, etc) as well as the significance of PSA-test in various types of lesion are considered. PMID- 11765420 TI - Attack on America. PMID- 11765421 TI - Turning today's challenges into change. PMID- 11765419 TI - [Morphological characteristics of chronic endometritis]. AB - The immunohistochemical examination of 46 endometrial biopsies from women with chronic endometritis (CE) suffering from habitual abortions has found disturbance of correlations between various types of immunocompetent cells with domination of T-suppressors, increased accumulation of IgG on the surface of glandular epithelium. In CE, thickening of spiral arteries occurs not because of sclerosis but due to muscular hypertrophy, endometrial stromal-epithelial relations are impaired. Alterations in the distribution of the extracellular matrix components indicate defective endometrium maturation which may lead to inadequate oocyte implantation. PMID- 11765418 TI - [Pathomorphology of the kidneys in acute renal failure caused by thrombotic microangiopathy in pregnancy, during labor and in puerperas]. AB - The review of literature on acute renal deficiency in pregnancy, delivery and post-delivery period is presented. PMID- 11765422 TI - State and school activities. PMID- 11765423 TI - Who supports the nursing profession? PMID- 11765424 TI - Take the challenge. Volunteer with the American Red Cross. PMID- 11765425 TI - Becoming politically savvy. A past NSNA president highlights her inspired path to leadership.... PMID- 11765426 TI - Political action starts with you. PMID- 11765427 TI - Behind the scenes of resolution writing. How Arizona nursing students got tobacco settlement legislation off the ground. PMID- 11765428 TI - Increasing political awareness. PMID- 11765430 TI - Lessons learned. PMID- 11765429 TI - The nurse anesthetist supervision issue. A case study in grassroots organizing.... PMID- 11765431 TI - Facing the AIDS epidemic in Africa. PMID- 11765432 TI - Nursing within a digital society. PMID- 11765433 TI - Inquest produces change. PMID- 11765434 TI - Creating primary health care practice opportunities for nursing students. PMID- 11765435 TI - Electronic documentation on a psychiatric unit. PMID- 11765436 TI - Improving care for patients with gastrostomy tubes. PMID- 11765437 TI - [Own experience in supracricoid laryngectomy with GHP and GHEP type of reconstruction due to larynx cancer]. AB - The results of the surgical treatment of the larynx cancer (glottic-supraglottic) by supracricoid laryngectomy with CHP and CHEP type of reconstruction were presented. Material consists of 160 cases (88 after CHP and 72 after CHEP). 5 years survival rate was obtained in over 71% of cases in all material. Decannulation was possible in 126 (79%) patients. Feeding tube removal before 4 weeks after operation was done in 139 (87%) cases. In subjective assessment all patients had social efficient speech. Favourable results of the treatment encourage wider application of supracricoid laryngectomy. PMID- 11765438 TI - [Laser cordectomy: treatment of precancerous stages of the larynx]. AB - Diagnostics and treatments of precancerous states of cancer of larynx will demand in select chances the multistages treatment AIM: In work one priced radicality and efficiencies of treatment of precancerous stages of larynx with method of carbone dioxide laser cordectomy. The retrospective examination was executed of years 1991-2000 imicrosurgical interventions of larynx--in talked over period one executed 308 of surgical interventions with use of laser CO2, in number this 41 of interventions were partial laser cordectomies in stages with precancerous changes on the vocal cords. In chances of extensive precancerous changes of vocal cords in sorted chances not one should limit oneself to receiving of specimens from several localization, but change to remove in wholes. Permits this on obtainment radicality of intervention with possibility of obtainment the large material to histopathological investigations. PMID- 11765439 TI - [The problem of cervical metastases in vocal cord carcinoma]. AB - On the base of 755 cases of glottic cancer, the occurrence and prognostic importance of lymph node metastases were analysed. Metastases of the vocal cord cancer to cervical lymph nodes are rare. In our material amounted 9.13%. Number of metastatic lymph nodes and N factor influenced the lymph node recurrency. It is not, however, dependence statistically. Surgical treatment of the glottic cancer with various degree of advancement secures good oncological results. In our material 3 and 5 years survival rate accounted to 71.33% and 59.31%. The clinical advancement of the glottic neoplasm does not influence in statistically essential way the increase of metastases to regional lymph nodes. PMID- 11765440 TI - [Human papillomavirus (HPV) in the laryngeal carcinoma]. AB - Epidemiological data and results of molecular studies suggest that human papillomavirus has been considered a risk factor in upper respiratory tract cancers. 10 out of 23 studied cases of laryngeal carcinoma revealed presence of HPV DNA (43.5%). The PCR and Hybrid Capture II test were used for the detection of viral DNA. PMID- 11765441 TI - [The role of Epstein-Barr virus (EBV) infection in carcinogenesis of palatine tonsil carcinoma (PTC)]. AB - OBJECTIVES: Casual link of Epstein-Barr Virus (EBV) and endemically manifesting nasopharyngeal carcinoma has been already well documented. Our study, conducted in Karol Marcinkowski University of Medical Sciences in Poznan, aimed at examining whether EBV infection occurs also in patients with another tumor, palatine tonsil malignant neoplasms. METHODS: The studies were performed on 20 patients, aged 32 to 80 years, in whom tonsil malignencies was diagnosed by histological methods. The treatment of choice was surgery. Sera of the patients was tested for EBV DNA (Sharp Signal System; Digene), IgM-anti-EBV antibodies (Behring), IgG-anti-EA antibodies (ETI-EA-G; Dia Sorin) and IgG-anti-VCA antibodies (ETI-VCA-G; Dia Sorin). RESULTS: Serological exponents of reactivated EBV infection (serum IgG-anti-EA and IgG-anti-VCA antibodies) were observed in 12 patients. In parallel, ten of the patients demonstrated EBV DNA. In the remaining 8 patients, three manifested past EBV infection (positive IgG-anti-VCA) and five probed to be EBV negative. CONCLUSIONS: The results indicated, that tonsil malignancies may be associated with EBV infection. PMID- 11765442 TI - [The orbito-zygomatic craniotomy in the treatment of giant tumor penetrating from maxillary-ethmoidal region to the anterior cranial fossa]. AB - The orbitozygomatic craniotomy was presented in resection of giant tumour of maxillary-ethmoidal region, orbital cavity and anterior cranial fossa. As a result of this approach the possibility of whole tumour resection was obtained. Also, easy closure of anterior fossa and avoidance of the facial deformation was achieved. PMID- 11765443 TI - [Nasal lavage, rhinomanometry and rhinoscopy in diagnosing occupational airway allergy]. AB - The aim of the study was to estimate the usefulness of nasal lavage, rhinomanometry and rhynoscopy in diagnosing occupational allergic rhinitis and bronchial asthma. 26 subjects with suspected bronchial asthma and allergic rhinitis due to occupational allergens were examined. Each subject had medical history collected and underwent physical examination, skin prick tests (SPT) with common and occupational allergens, determination of total and specific IgE, specific bronchial or nasal provocation with determination of spirometric parameters, morphological and biochemical changes in nasal lavage fluid (NLF). Moreover the anterior rhinomanometry and rhynoscopy were performed before and after the provocation. A significant increase in the percentage of eosinophils and albumin was observed in NLF up till 24 hr after the specific challenge, but only in the group of 16 subjects with diagnosed occupational airway allergy. The authors observed also the presence of mucosal oedema and rhinorrhea in this group of patients more frequently than in the group of patients without diagnosed occupational airway disease. No significant changes were observed in the frequency of positive rhinomanometry test between the analysed groups of patients. PMID- 11765444 TI - [The quality of life in head and neck cancer patients: description of randomized examination formula based on standardized questionnaires EORTC QLQ C-30, EORTC QTQ-H-N35 and Kiel Questionnaire]. AB - The notion of quality of life (QL) was first introduced in the US in the 50-ies. This notion is much broader then health, it is a personal, subjective feeling of well-being that comes from actual, widely-meant life experiences. The QL is not a measurable value, however, it may be assessed by means of appropriate indices. In the contemporary holistic attitude to a patient, in modern oncology, QL has become a parameter of equal importance to other values characterizing the treatment success, as important as numbers describing e.g. mean survival, disease free survival, or neoplasm controlled survival. Head and neck neoplasms bring about deterioration of the basic functions of the organism such as: breathing, swallowing, speaking and senses: hearing, taste and smell. Application of treatment may intensify pain, dyspnea, hoarseness or cause any kind of discomfort. It influences directly the patients' family and social life. Comparison of QL of patients treated for larynx, tongue, tonsill, glands, and paranasal sinuses neoplasms depending on localisation of primary foci, advancement of the disease, the applied treatment and its radicality, age, sex, place of living (town/country), and educational level. Correlation between the subjectively assessed QL and the objectively evaluated condition of the patient is measured. In ENT Dept. K. Marcinkowski University of Medical Sciences 46 patients were examined from May to September 2000. EORTC QLQ C-30, EORTC QLQ-Head and Neck and HAD scale were used. Kiel Questionnaire was introduced in September. The main reason for introducing it was the fact, that surgery is the method of choice in the treatment of head and neck malignancies in our Dept. The team composed of a psychologist and an ENT doctor has been working together on objective assessment of each patient. The QL assessment may be of practical importance when trying to improve the model of health care in cases of oncological patients. This knowledge enables us to learn how the accompanying side effects of therapy influence the QL of our patients, and how these problems may be overcome by proper education, advice, and support provided by the qualified staff. The authors are evaluating the QL in the period of 2, 6 months and 1 year after surgery in patients not supported psychologically. Our goal, in the future, is to introduce the psychological treatment, i.e. repetitive meetings in small groups, conducted by a psychologist. We have contacted 4 major ENT centers in Poland in order to coordinate the research on detailed assessment of QL in Head and Neck Cancer Patients in Poland. The results will be presented in the further publications. PMID- 11765445 TI - [Intracranial complications of sinusitis in the material of the Otolaryngology Department, K. Marcinkowski University of Medical Sciences in Poznan in the years 1964-1999]. AB - In the period of 35 years 25 patients with intracranial complications of paranasal sinusitis were treated in the Department of Otolaryngology of the Karol Marcinkowski University School of Medical Sciences in Poznan. In the past 15 years the number of complications decreased annually by half. Intracranial sinusal complications were more frequently present in young men. In 25 patients abscesses of the frontal lobe and epidural abscesses were most often diagnosed. Surgical treatment was carried out in each case when the inflammation process spread into the bony parts or into intracranial space. The method of choice in treatment of frontal lobe abscess and subdural abscesses is elimination of sinuses inflammatory foci with a simultaneous evacuation of the abscess by puncturing of the abscess and gradual exchange of its content into antibiotic solution. Intensive antibiotic therapy was carried out for the period of 4 weeks. Mortality rate in our material concerned patients with the brain frontal lobe abscesses and amounted to 12%. In the last 15 years we succeeded to treat all 17 patients. PMID- 11765446 TI - Antibiotic sensitivity of bacteria isolated in 1998 and 1999 from patients with infections of upper airways residing in Western Pomerania. AB - Sensitivity to antibiotics of the most common pathogens isolated from the upper airways in north-west part of Poland shown significant regional variation. The rise in resistance to penicillin for Streptococcus pneumoniae (to 22%) and to macrolides for Streptococcus pyogenes, Streptococcus pneumoniae and Staphylococcus aureus was observed. No differences in sensitivity have been found between pathogens isolated from hospital and ambulatory patients. PMID- 11765447 TI - [Preliminary assessment of the role of IL-5 in the pathogenesis of nasal polyps]. AB - Preliminary results of IL-5 levels in homogenates derived from nasal polyps tissue are presented. The IL-5 concentration was assessed by immunoenzymatic method (ELISA, R&D, Systems Minneapolis). 26 patients at age 21-60 years were examined. IL-5 cevels were higher in polips with allergic and were examined. IL-5 levels were higher in polips with allergic and aspirin idiocracy background compared with inflammatory polips. In addition, IL-5 levels were increased in recurrent polips. PMID- 11765448 TI - [Cochleography and cochlear view as the way of assessment of successful surgical inner ear implantation]. AB - 115 cochlear implantation were performed in ENT Department Karol Marcinkowski University of Medical Sciences in Poznan in 1994-2001. Nucleus Mini System 22 and Nucleus 24 of Cochlear Ltd were used in these operations. Two approaches were performed: middle fossa approach in one case and traditional one. The aim of this study was evaluation of cochleogram and cochlear view as the ways of assessment of successful inner ear implantation. One of X-ray projection were performed in implanted patients 24 hours after implantation. In cochleograms the degree of electrodes rotation in cochlea was calculated. The number of inserted electrodes in cochlea was calculated in cochler view projection. Described X-ray projection were performed in 70 patients. On X-ray projection (cochleograms) rotation degree of electrodes in majority were equal or higher than 250 grades (according to literature it is sufficient for successful speech rehabilitation). X-ray projection--cochlear view confirmed full insertion of electrode. PMID- 11765449 TI - [Familial occurrence of hearing loss following streptomycin (SM) treatment]. AB - References data indicate the probability of inheritance of predisposition to post streptomycin hearing loss. Ototoxicity after SM is transmitted by women. It is considered as autosomal dominant inheritance, but the transmission to the next generation is not explained by the Mendelian inheritance rule. The aim of our presentation is showing different kinds of hearing loss after SM occurring in siblings with probable inherited susceptibility to SM. PMID- 11765450 TI - [Immuno-genetic significance in sensorineural hearing loss (SNHL) in the light of our own investigations]. AB - The immunogenetic analysis in 152 patients with sensorineural hearing loss (SNHL) was studied. HLA class I antigens and haplotypes were calculated on the basis of typical linkage between HLA-A, -B, and C loci. Soluble form of HLA antigens (sHLA I) in blood serum in a semiquantitative microabsorption test according to McLean et al. were also determined. It was found that the frequency of HLA-A2, -A25(10), -B39(16), -Cw5, and -Cw7 were different in patients with SNHL in compared to the control group (n = 1554). This deference's were highly significant, especially for HLA-Cw7 antigens (chi 2 = 88.88; p < 0.0000...1). The frequency of haplotype HLA-A25-B18-Cw7 in patients was also different (f = 362 x 10(4) vs 51 x 10(4)), and highly significant compared to the healthy individuals (n = 1944) (chi 2 = 27.37; p < 0.0000...1). Among 23 typed HLA class I antigens, significantly higher mean level was observed for 14 sHLA antigens then in control group (n = 248). The levels of sHLA-I antigens in patients sera may suggests participation of sHLA molecules in etiopathogenesis of SNHL. This hypothesis may indicate the existence of autoimmunogenetic background of SNHL within high concentrations of certain sHLA-I antigens. PMID- 11765451 TI - [The case of Wegener's granulomatosis of the nose, larynx and ear]. AB - We have described a rare case of Wegener's granulomatosis in our 41-year old patient, located in the nose, larynx and ear. The disease usually presents as a triad of respiratory, vascular and kidney location. It may occur as a rapid or indolent progress. We have shown in our paper diagnostic difficulties connected with this disease. The biopsies of involved organs and blood tests are the best steps of establish proper diagnosis. Antineutrophil cytoplasmic antibodies (ANCA) are typical markers of Wegeners's granulomatosis. The conservative therapy including immunosuppression and surgical treatment (laserotherapy) are main methods of management. Our patient was given antibiotic therapy, and immunosuppressive therapy. Her condition improved during the first hospitalisation. Remission lasted very short, and she was admitted to the hospital again and underwent intensive investigations and therapy. We observed dyspnea caused by subglottic stenosis. The histologic examination of the tracheal mucosa showed granulomatous inflammation. After intensive therapy our patient felt better. She has been in our records till now, we observe no progress of disease. Finally, we would like to pay attention to the fact, that early diagnosis is important to prevent complications such subglottic stenosis which can lead to death. PMID- 11765452 TI - [Necrotizing sialometaplasia. Case report]. AB - The authors present a rare case of inflammatory disease of submandibular salivary gland (necrotizing sialometaplasia), in which the histopathological examination was of particular value while estimating the final diagnosis. Review of world literature concerning this disease was made. PMID- 11765453 TI - [Laryngeal chondromas: review of the literature and report of three cases]. AB - The authors present three cases of laryngeal chondroma. One of them was localized on the thyroid cartilage and on the cricoid cartilage in two cases. Direct laryngoscopy and biopsy make diagnosis. But it is not always easy to obtain an adequate biopsy sample from cartilaginous tumors because of their submucosal location and consistency. The radiological findings turned out to be very helpful in chondroma of the larynx. All our patients were treated surgically, one of them performed a partial laryngectomy, and two required a total laryngectomy. Laryngeal chondromas are very rare. As well a brief review of the literature is presented. PMID- 11765454 TI - [Pleomorphic adenoma of atypical location]. AB - The authors described 2 cases of adenoma pleomorphum localised out of salivary glands. One of them was located in mucous of cheek and another one on the palate. All patients were treated surgically. PMID- 11765455 TI - [The great investigators of the ear anatomy]. AB - There was presented the galaxy of famous anatomists which had investigated the structure of the ear and the temporal bone. There were shown the anatomical parts of the ear, which were named from the names of their discoverers. PMID- 11765456 TI - [The assessment of surgical treatment of otosclerosis by various methods at the Chair and in the Clinic of Otorhinolaryngology II, Medical department of the Medical Academy in Warsaw in the years 1972-1992]. PMID- 11765457 TI - [Comparative effectiveness of different methods of quantum hemotherapy in the treatment of juvenile diabetic retinopathy]. AB - Effects of ultraviolet exposure of the blood (UVEB), intravenous laser exposure of the blood (IVLEB), and transcutaneous magnetic laser exposure of the blood (TMLEB) on ocular functions, microcirculation, and hemodynamics were studied in 79 patients with juvenile diabetic retinopathy. All these treatments had a nonspecific positive effect on the spatial contrast sensitivity, microcirculation, and choroid hemodynamics of the eye. Correcting mainly intravascular changes in the microcirculatory bed, quantum hemotherapy methods are pathogenetically justified in the treatment and prevention of tissue ischemia in diabetic involvement of the organ of vision. Results of noninvasive TMLEB with generalized and local effects were statistically similar to results of invasive UVEB and IVLEB. PMID- 11765458 TI - [Results of intraocular lens implantation in cataract complicated by medium and high myopia]. AB - Results of surgical treatment of cataract complicated by medium and high myopia are analyzed. The main group consisted of 90 patients (96 eyes) subjected to extracapsular cataract extraction with implantation of posterior-chamber intraocular lenses and the reference group of 128 patients in whom cataract was extracted without implantation of artificial lens. The study included creation of a mathematical model of myopic eye with estimation of pressure fluctuations in various zones of the eye, developing during transposition of the vitreous during patient's movements (head movements, jumps, falling) and the damping effect of the lens in the ocular system. It was proven by mathematical calculations that transpositions of jelly fractions of the vitreous decreased by 70% in an eye with the lens in comparison with their transposition in aphakia. Clinical studies demonstrated the efficiency of intraocular correction of aphakia in high myopia: implantation of an intraocular lens decreases the risk of detachment of the retina during the postoperative period and helps attain the desired refraction. PMID- 11765459 TI - [Intraocular lens for correction of aphakia in cataract extraction through a small incision]. AB - The purpose of this study was to create an intraocular lens (IOL) reliably fixed in the capsular sac and convenient for implantation through a tunnel incision. Our design consists from a biconcave lens 5 mm in diameter and 2 vis-a-vis C shaped open haptic elements at an angle of 110 degrees to the optic component. The total diameter of IOL is 12 mm. The lens is made from rigid material (oligocarbonate methacrylate). IOLs of this design were implanted in 164 eyes. No complications were recorded. The studies indicate that this design ensures good mobility and elasticity of the supporting elements of the lens at the site of their bending and connection to the optic part. This results in even and most complete filling of the capsular sac equator with supporting elements and the maximal retraction of the sac, which creates conditions for reliable fixation of IOL, prevents development of fibrous changes, decentration and dislocation in the postoperative period. PMID- 11765460 TI - [Possibilities and results of photorefraction operations for myopia after retinal detachment surgery]. AB - Pathological changes in the retina in myopia of 1.5-17 diopters are analyzed, based on analysis of more than 4800 cases. Detachments of the retina were responsible for 0.5% cases. Photocoagulation of the retina was carried out using 2 lasers: diode DC-3000 NIDEK (790-830 nm) and Nd-YAG Alcon (532 nm). Photorefraction operations of two types (photorefraction keratectomy and LASIK) were carried out on a Nidek EC-5000 laser. The results evidence a possibility of photorefraction operations for correction of myopia 6 months to 11 years after a previous intervention for detachment of the retina (21 operations). Visual acuity without correction was 0.69 +/- 0.08, spherical equivalent of clinical refraction 0.80 +/- 0.34. Repeated laser coagulation at the retinal periphery for blocking newly forming ruptures was needed in 14.2% cases. No relapses occurred during 3 years postoperation. PMID- 11765461 TI - [Structure of complications of specialized excimer laser keratomileusis in correction of myopia]. AB - Complications of LASIK carried out at Medinvest Center of Laser Correction of Vision (Chelyabinsk) on an EC-500 eximer laser (NIDEK, Japan) with LSK microkeratome Evolution-2 (Moria, France) in 498 patients (984 eyes) for correction of myopia and myopic astigmatism are analyzed. Myopia varied from 2.5 to 17 diopters (mean 7.38 +/- 1.31), astigmatism 0.5-4.5 (mean 1.57 +/- 0.87). No complications occurred during the operation in 84.9% cases. Intraoperative and postoperative complications were observed in 15.1% patients. The intraoperative (10.1%) were hemorrhage from the marginal perilimbic corneal vessels, desquamation of epithelium, flap deficiency, complete dissection of the flap; postoperative (5%) were irregular astigmatism, hyper- and hypocorrection. Hence, our data indicate that LASIK is an effective method for surgical correction of myopia. PMID- 11765462 TI - [Changes in the ocular and orbital blood flow in patients with retinal detachment treated surgically]. AB - Sixty-eight patients with dystrophic regmatogenic detachment of the retina and 78 controls with different clinical refraction were examined by triplex scanning of the eyeball. Bloodflow parameters in the orbital artery, central retinal artery, posterior short ciliary arteries were evaluated before and in various periods after the operation. Characteristics of the bloodflow in the ocular and orbital arteries in myopia, detachment of the retina in the presence of myopic and emmetropic refraction, proliferative vitreoretinopathy of various degrees and patterns of its progress during the postoperative period were determined and time course of bloodflow parameters evaluated in some types of interventions. Hemodynamic parameters of the orbital artery and posterior short ciliary arteries were significantly related to the degree of proliferative vitreoretinopathy and its postoperative progress. PMID- 11765464 TI - [Possibilities of special correction in restoration of reading capacity in poorly sighted patients]. AB - A total of 1012 patients aged 6-94 years (31.9% aged under 19 years, 25.2% aged 20-60 years, and 42.9% aged over 60) with poor sight, 83% of whom could not read book type, were examined. Corrected far visual acuity was 0.03-0.35, in 52.7% of these 0.1-0.2 and in 38.2% less than 0.1. The most incident diseases were retinal and optic nerve disease (40.6%), complicated myopia (15%), congenital ocular diseases (17.3%), aphakia (9.8%), and glaucoma (7.9%). In order to select correction, near visual acuity, reading acuity, and reading speed were evaluated. Optic magnifiers, such as hyperocular eyeglasses, magnifying glasses of different types (supporting, applied, special, manual, and telescopic) were used for correction. Four-fold magnifiers were prescribed most often (67.3%). Optic magnifiers allowed reading in 78% cases. The decisive factors of the device efficiency were reading acuity (no more than 48 points) and reading speed (at least 200 signs/min). Ocular disease, visual field status, patient's age and psychosomatic state, and technological characteristics of the device are also important factors. PMID- 11765463 TI - [Differentiated conservative treatment of ocular ischemic syndrome]. AB - The efficiency of differentiated conservative treatment of ocular ischemic syndrome (OIS) was studied. In acute course, drugs improving bloodflow and blood rheology were prescribed. In patients with primary chronic pattern of the syndrome, drugs correcting microcirculation, transcapillary metabolism, and improving metabolism in ischemic tissues were used. After the treatment, visual acuity increased by at least 0.1 diopter in 12.8% patients with acute OIS, the peripheral visual field extended by 21.5% in 11.5%, and the function of the optic nerve improved in 10.5%. Comparative evaluation of results of therapy showed better efficiency in patients with the acute course. PMID- 11765465 TI - [Formation of idiopathic macular holes]. AB - Sixty-eight patients (136 eyes) with idiopathic macular hole (IMH) were examined, using optic coherent tomography. 91% of these patients were women, mean age 66.6 years. Preholes were detected in 14 eyes, lamellar ruptures in 11, and perforating ruptures in 78 eyes. Specific functional and morphological changes in the retina, vitreous, and vascular membrane were detected. Three main mechanisms of IMH formation were distinguished. Conceptual scheme of the pathogenesis of this condition was developed and a new more complete pathogenetically justified classification of IMH is offered, which helps more objectively diagnose, predict the functional outcome, determine the treatment strategy, and evaluate the efficiency of surgery. PMID- 11765466 TI - [Nitrogen oxide in the pathogenesis of glaucoma and cataract]. AB - The content of nitrite (final metabolite of nitroradical) was measured in aqueous humor of patients with glaucoma and cataract. The level of NO formation is increased at the initial stage of glaucoma and decreases with the disease progress. A direct correlation between the level of nitrite in aqueous humor and coefficient of easiness of its discharge was detected. Cataract is associated with a high level of nitrite in intraocular fluid. The results are discussed from the viewpoint of ocular hydro--and hemodynamic regulation and NO involvement in the free radical oxidation reactions, playing an important role in the pathogenesis of both diseases. PMID- 11765467 TI - [Prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in perforating wounds of the eyes and their time course during local antioxidant treatment]. AB - Lipid peroxidation parameters malonic dialdehyde (MDA) and dienic conjugates (DC) and antioxidant defense (AOD) values superoxide dismutase (SOD), catalase, alpha tocopherol were measured in the blood neutrophils and lacrimal fluid of 66 patients on days 1-2, 7-8, 14-15, and 21-22 after perforating wound of first, second, third, and fourth degree of severity according to P, 1. Lebekhov and in repeated injury, and the time course of these parameters during local treatment with therapeutic films with emoxipin and emoxipin + piridoxine was evaluated. A stable increase of MDA and DC levels in blood neutrophils, decrease of catalase, SOD, and alpha-tocopherol levels in blood neutrophils, and decrease of catalase enzymes and SOD activities in the lacrimal fluid of injured eye starting from days 7-8 are prognostically unfavorable signs. These data prompt the use of local and systemic treatment with antioxidants (emoxipin, tocopherol, etc.) in perforating wounds starting from the first days after the injury. Good clinical and antioxidant effect was observed after treatment with ocular therapeutic films with emoxipin and piridoxine. PMID- 11765468 TI - [Contents of T-lymphocytes and expression of intercellular adhesion molecule ICAM 1 in the retina and choroid in diabetic retinopathy]. AB - The authors analyze the relationships between individual immune components at a cellular level and evaluate their significance in development of proliferative processes. Ocular tissues from diabetics who died from cardiovascular failure and stroke and from subjects who died from traumas (control) were examined by immunohistochemical methods. The results evidence increased counts of T lymphocytes and high expression of ICAM-1 in ocular tissues of diabetics, which suggests an important role of these factors in development of diabetic retinopathy. PMID- 11765469 TI - [Experimental study of the effectiveness of the use of imunofan in the treatment of viral diseases of the eye]. AB - The efficiency of local therapy of ocular inflammations with a new drug immunophane was evaluated in experiments. Ophthalmological and morphological methods were used in the study. Experiments on 30 Wistar rats (60 eyes) demonstrated the absence of toxic effect on intact ocular tissues. Therapeutic efficiency of immunophane was demonstrated in 13 rabbits (26 eyes) with ophthalmic herpes. The advantages of subconjunctival injections of immunophane in comparison with instillations of leukocytic interferon are demonstrated. PMID- 11765470 TI - [Immune disorders in patients with dystrophic conditions of the posterior segment of the eye and chronic alcoholism]. AB - A total of 193 patients with chronic alcoholism aged 30-65 years were examined. Optic nerve abnormalities were detected in 30 (15.5%) and degenerative condition of the retina in 42 (21.8%) patients. Ocular diseases were detected in 72 (37.3%) examined chronic alcoholics. Disorders of total and local immunity of the eye contribute to the development of the above diseases. These changes were more pronounced in chronic alcoholics with visual analyzer abnormalities. These data can be useful in development of pathogenetic therapy of ocular diseases. PMID- 11765471 TI - [Laser coagulation and cryocoagulation in the treatment of isolated retinal angiitis]. AB - Isolated retinal vasculitis (IRV) is a form of retinal vasculitis without other inflammations of the eye or systemic vasculitis. Occlusion of retinal vessels without subsequent retinal ischemia and neovascularization is one of the main problems in the management of such patients. Laser photocoagulation seems to be a method to control this problem. Argon laser photocoagulation was used in the treatment of 34 IRV patients (56 eyes) (29 men and 15 women aged 25-41 years, mean age 32.9 +/- 5.2 years). A total of 168 sessions were carried out. Regression of neovascularization was achieved in 29 of 44 eyes (79.5%). Additional cryotherapy had to be performed in 15 eyes, good results were attained in 9 eyes (60%). Patients treated with prednisolone in a daily dose of 10-20 mg during laser coagulation had IRV recurrences more rarely than those treated with lower doses (5 mg) (0-6.7% vs. 50%, p < 0.0013), those treated with metipred depot for 7-14 days (0-6.7% vs. 53.8-66.6%, p < 0.0023), or untreated ones (0 6.7% vs. 73.9%, p < 0.0000). PMID- 11765472 TI - [Treatment of chlamydial conjunctivitis]. AB - A new method for treating chlamydial conjunctivitis consists in injections of ciprofloxacine for intravenous injections, which is injected (1 ml) under the inferior vault of the conjunctiva on novocaine pad (0.5 ml 0.5% solution) and intravenously by drip infusion (99 ml) twice daily for 7-10 days. The treatment led to clinical cure in all patients, no relapses were observed. This method ensures a high therapeutic effect and accelerates the recovery of patients with chlamydial conjunctivitis by 4.6 days. The method is recommended for patients with complicated forms of chlamydial conjunctivitis in severe and protracted cases with concomitant urogenital chlamydial infection and concomitant chronic gastrointestinal diseases, when oral antibiotic therapy is undesirable or precluded. PMID- 11765474 TI - [Acanthamoeba lesions of the cornea]. PMID- 11765473 TI - [A case of epidemic keratoconjunctivitis complicated by gonococcal infection]. PMID- 11765475 TI - [Delayed visual maturing in infants: differential diagnosis and treatment strategy]. AB - Results of long observations of 7 infants with delayed visual maturing, diagnosed at the age of 2-4 months by ophthalmological, electrophysiological, radiological methods and registration of electroretinogram (ERG) and visual evoked potentials (VEP), are analyzed. Delay of visual maturing is characterized by disorders of behavioral visual reactions in neonates with emmetropia, absence of ocular disease and oculomotor system, normal ERG and VEP in response to a light flash or 14-110' patterns, and absence of changes in the postgenicular tract detected by radiological examination. Diagnostic criteria of delayed visual maturing and symptoms important for differential diagnosis are defined. PMID- 11765476 TI - [Tumor necrosis factor alpha in chronic heart failure. Clinical manifestation and therapeutic possibilities]. AB - BACKGROUND: Chronic heart failure (CHF) may be seen as a multi-system disorder with its origin in the heart but including many extracardiac manifestations. Immunological abnormalities are recognized in this context, in particular, changes in the expression of mediators of the innate immune response. IMPORTANCE OF TNF: Higher levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF) are found in the circulation and in the myocardium of patients with chronic heart failure than in controls. TNF has been implicated in a number of pathophysiological processes that are thought to be important to the progression of chronic heart failure. Therapies directed against this cytokine might therefore represent a novel approach to heart failure management. PMID- 11765477 TI - [Lactate in cardiac rehabilitation]. AB - BACKGROUND: Training increases work capacity and concomitantly quality of life, and also, according to new data, the life expectancy of patients with coronary heart disease and heart failure. At the same time, the importance of adequate training intensity increases aiming at low complications and high efficacy. ASSESSMENT OF EXERCISE CAPACITY: The objective of the present work is to define objective training guidance parameters in cardiac rehabilitation. Maximal exercise capacity must be distinguished from the performance without symptoms of oxygen deficit. The latter used to be early surpassed in untreated stabile angina pectoris. Within the last decade optimized therapy often yields a cardiac performance limit above the anaerobic threshold derived from lactate measurements. The concepts of aerobic and anaerobic thresholds derived from the lactate performance curve are introduced and modified leaving the 4 mmol/l lactate threshold concept to meet the criteria for performance capacity and breaking point in cardiac patients. The relationship to threshold concepts derived from spirometric data is mentioned as well as from stress hormones. The heart rate at the anaerobic threshold measured at treadmill ergometry systematically lies above the one from bicycle ergometry. Lactate increases faster with advancing age and the anaerobic threshold is earlier reached and progressively so because of the reduced muscle mass and reduced endurance capacity of people of the industrialized countries. IMPORTANCE: The determination of the anaerobic threshold as an objective criteria independent of motivation leads to training control, as shown by an example. Ineffective training above the threshold giving rise to catecholamines can be avoided by lactate performance diagnostic. Additionally, the success of rehabilitation measures can objectively be quantified and documented much better from the threshold work capacity than from maximal exercise tolerance. Preliminary reports indicate the importance of lactate diagnostics for rehabilitation guidance in heart failure. PMID- 11765478 TI - [Calcified plaque of the extracranial carotid arteries in comparison with traditional risk factors as a predictor for relevant coronary artery stenoses]. AB - BACKGROUND: Intima-media thickness (IMT) of carotid arteries, measured by vascular ultrasound, has widely been used as a surrogate marker for coronary atherosclerosis. As recent studies showed significant but only weak correlation between IMT and coronary artery stenoses, this study evaluated calcified plaques in the extracranial carotid arteries as a reasonable marker for coronary artery disease. PATIENTS AND METHOD: 139 patients underwent cardiac catheterization with selective coronary angiography and ultrasound examination (B-mode, standard Doppler, color Doppler) of the carotid arteries. In case of calcified plaques number and distribution among the extracranial cerebral arteries were determined (Figure 1). Coronary angiograms were analyzed for disease severity and extent (number of main vessels with > 50% stenosis). Besides the traditional vascular risk factors hypertension, diabetes, smoking and hypercholesterolemia as well as body mass index, age and sex were analyzed. RESULTS: Calcified plaques of carotid arteries were significantly correlated (r = 0.502, p < 0.001) with coronary artery stenoses as well as hypercholesterolemia (r = 0.410, p < 0.001), increasing age (r = 0.406, p < 0.001) and diabetes (r = 0.290, p < 0.001) in contrast to hypertension (r = 0.125, p = 0.075), smoking status (r = -0.043, p = 0.311), body mass index (r = -0.122, p = 0.083) and male sex (r = -0.103, p = 0.114) (Table 1). The number of calcified plaques was significantly correlated (r = 0.568, p < 0.001) with severity and extent of coronary artery disease, too (Figure 2). For two and more calcified plaques sensitivity concerning coronary artery stenoses was 80%, specificity 75%, positive predictive value 83%, negative predictive value 73% (Table 2). Multiple stepwise regression analysis was performed for all eight variables (calcified plaques, hypercholestrolemia, diabetes, hypertension, smoking status, age, sex, body mass index). Including calcified plaques the predictive value of all factors was higher (r = 0.644 to r = 0.607). CONCLUSIONS: Determination of calcified carotid plaques by ultrasound is useful to improve the predictive value of risk factor-based multivariate models based on traditional risk factors. PMID- 11765479 TI - [Aortic valve structures as landmarks for determining coronary artery ostia in transthoracic echocardiography]. AB - BACKGROUND: Occasionally, coronary arteries are recorded in transthoracal echocardiography. The question was if this modality could be used as non-invasive screening method of the coronaries. A prerequisite for this is an exact and reproducible measurement of the origin of the coronary arteries. MATERIAL AND METHOD: The topography of the coronary ostia in relation to the aortic valve was examined morphometrically in the aortae of 20 embalmed cadavers and 50 patients of a cardiologist's practice who underwent transthoracal echocardiography. RESULTS: In all cases, the coronary arterial orifices were located eccentrically in the coronary sinus, shifted to the non-coronary aortic sinus. The distance between left coronary orifice to the commissure of the left and the right semilunar valvula was 13.3 mm on average in the anatomical measurements, whereas in the echocardiography this distance was 14.3 mm. The distance between the left ostium and the attachment of the left and the posterior semilunar valvula 9.4 mm, corresponding to 11.6 mm in echocardiography. The distance between right coronary orifice and the attachment of the right and the left semilunar valvula was 18.0 and 17.3 mm respectively, and the distance between right coronary orifice and the commissure of the right and the posterior semilunar valvula accounted for 8.5 and 9.7 mm respectively. On the average, the ostia were located 3.9 mm below the level of the sinotubular junction. Multiple ostia occurred in 65%, 92% of these were in the right coronary aortic sinus, shifted from the main orifice to the attachment of the right and the left semilunar valvula. CONCLUSION: In the cardiologist's routine, the attachments of the aortic leaflets proved to be very useful as landmarks. The coronary arterial orifices have been educible in nearly all cases. These results show that transthoracal echocardiography may be used in the screening for coronary artery disease. PMID- 11765480 TI - [Quality of life and psychosocial factors during treatment with antihypertensive drugs. A comparison of captopril and quinapril in geriatric patients]. AB - BACKGROUND: There is an increasing prevalence of older adults (> 65 years) with hypertension and the need for antihypertensive medication. It is well established that elderly hypertensive patients benefit from drug treatment with regards to cardiovascular morbidity and mortality. Due to the comorbidity and reduced quality of life (QOL) in the elderly, drug-induced changes of well-being and QOL are especially important to maintain compliance and social abilities. Whereas in most studies different antihypertensive agents exerted similar influences on QOL, Captopril was found to be superior to other antihypertensives in some trials. PATIENTS AND METHOD: In this controlled non-randomized study 100 elderly hypertensive patients (mean age 75.4 +/- 7.2 years; 56% female) were treated with Captopril (25-50 mg twice daily) or the newer ACE-inhibitor Quinapril (5-20 mg per day). Blood pressure and QOL were recorded initially and after 6 months, assessment of QOL was based on a validated questionnaire (PLC). RESULTS: Blood pressure fell from 153/82 mm Hg to 142/80 mm Hg with Captopril and 154/82 to 142/80 mm Hg [corrected] with Quinapril. An improvement of QOL was only seen with Quinapril, mainly due to better mood and lower depression scores. Analysis of underlying psychosocial factors on QOL found lack of social support, female sex and a current life event as additional significant negative influences on QOL. CONCLUSION: A favorable antidepressive effect of Quinapril in elderly hypertensive patients is concluded and should be studied in further investigations. PMID- 11765481 TI - Spontaneous left ventricular hypertrabeculation in dystrophin duplication based Becker's muscular dystrophy. AB - BACKGROUND: Left ventricular hypertrabeculation is frequently associated with neuromuscular disorders. Whether left ventricular hypertrabeculation in these patients is congenital or develops during lifetime, is unknown. CASE REPORT: In a 65-year-old man with Becker's muscular dystrophy, due to a duplication in the dystrophin gene on chromosome Xq21 (dystrophin molecular weight: 500 kD), left ventricular hypertrabeculation was detected on transthoracic echocardiography although being absent in repeated previous echocardiographic examinations. Additionally, there was thickening of the left ventricular myocardium. The spontaneous occurrence of left ventricular hypertrabeculation was interpreted as progression of cardiac involvement in Becker's muscular dystrophy. CONCLUSION: Left ventricular hypertrabeculation may not exclusively be congenital, but may occasionally develop spontaneously during lifetime, being interpreted as progression of cardiac involvement in Becker's muscular dystrophy. PMID- 11765482 TI - [Acute thrombosis of a mechanical heart valve caused by inadequate anticoagulation with low molecular weight heparin]. AB - CASE REPORT: A 55-year-old woman with a mechanical aortic prosthesis was admitted with pulmonary edema and suspect of valvular malfunction. The patient had a anticoagulation therapy at the time with low-molecular-weight heparin only. Echocardiography confirmed a failing mobility of a prosthetic valve leaflet. Emergency aortic valve replacement was performed. CONCLUSION: According to international approved guidelines an adequate anticoagulation after mechanical prosthetic heart valve replacement is provided either by oral anticoagulants, or, in the case of pregnancy or surgical procedures, by unfractioned heparins. The use of low-molecular-weight heparin as sole anticoagulant remains a matter of controversy in the literature. In recent years low-molecular-weight heparins were mainly administered for prevention and treatment of deep vein thrombosis, pulmonary embolism, stroke, and instable angina. PMID- 11765483 TI - Dipyridamole-atropine-induced myocardial infarction in a patient with patent epicardial coronary arteries. AB - BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation. PMID- 11765484 TI - [Acute anterior wall infarct in a 31-year-old patient after administration of methylergometrin for peripartal vaginal hemorrhage]. AB - CASE REPORT: After administration methylergometrine 30 minutes after delivery for peripartal vaginal bleeding a 31-year-old female patient developed an acute anterior wall myocardial infarction. Coronary angiography 7 hours after beginning of the chest pain demonstrated a dissection with a large thrombus in the proximal left anterior descending artery, followed by a complete occlusion in the periphery of the vessel (Figure 1). After applying rtPA intravenously, coronary angiography showed 24 hours later an open vessel without thrombotic material (Figure 2). CONCLUSION: Coronary artery spasm induced by methylergometrine must be regarded as the main reason for the dissection and thrombus formation followed by a myocardial infarction. PMID- 11765485 TI - Public attitudes to primary care reform. PMID- 11765486 TI - Primary care visits: how many doctors do people see? PMID- 11765487 TI - The future of healthcare in Canada. Interview by Peggy Leatt. PMID- 11765488 TI - Primary healthcare reform: ideas for renewal. PMID- 11765489 TI - Reforming primary care--better to build on the best. PMID- 11765490 TI - The National Health Service approach to primary care. PMID- 11765491 TI - Use of physician assistants and nurse practitioners in primary care, 1995-1999. AB - Federal policies and state legislation in the United States encourage the use of physician assistants (PAs) and nurse practitioners (NPs) in primary care, although the nature of their work has not been fully analyzed. This article analyzes primary care physician office-encounter data from the 1995-1999 National Ambulatory Medical Care Surveys. About one-quarter of primary care office-based physicians used PAs and/or NPs for an average of 11% of visits. The mean age of patients seen by physicians was greater than that for PAs or NPs. NPs provided counselling/education during a higher proportion of visits than did PAs or physicians. Overall, this study suggests that PAs and NPs are providing primary care in a way that is similar to physician care. PMID- 11765492 TI - Will primary healthcare reform improve health? PMID- 11765493 TI - Repairing and renewing nursing workplaces. PMID- 11765494 TI - Physicians as leaders: what does it take to excel? PMID- 11765495 TI - "Change is inevitable and desirable": an interview with Ontario's Minister of Health and Long-Term Care. Interview by Peggy Leatt. PMID- 11765496 TI - Utilization management in inpatient psychiatry. PMID- 11765497 TI - Implementing a privacy compliance program in your hospital. PMID- 11765498 TI - Older, wiser and more anxious. PMID- 11765499 TI - Rwandan sorrow. PMID- 11765500 TI - Victory for Venter. PMID- 11765501 TI - Who owns the genome? Battle pending. PMID- 11765502 TI - Silent suffering. PMID- 11765503 TI - Survey: youth violence. The perception gap. PMID- 11765504 TI - Are you man enough? PMID- 11765505 TI - Men & their bodies. Never too buff. PMID- 11765506 TI - Vitamin overdose. PMID- 11765508 TI - Brave new cells. PMID- 11765507 TI - Abortion on trial, again. PMID- 11765509 TI - "Facts" on fiber. PMID- 11765510 TI - Video playground. PMID- 11765511 TI - Giuliani's choices. PMID- 11765512 TI - Parched earth. PMID- 11765513 TI - What mother nature teaches us about motherhood. PMID- 11765514 TI - Barefoot, pregnant and ready to fight. PMID- 11765515 TI - Reviving artificial hearts. PMID- 11765516 TI - Bubble-free. French doctors score a gene-therapy triumph. PMID- 11765517 TI - Mothers against guns. PMID- 11765518 TI - Brain gymnastics. PMID- 11765519 TI - Family fighting. PMID- 11765520 TI - Dangerous season. PMID- 11765521 TI - What will replace the tech economy? PMID- 11765522 TI - Will there be any hope for the poor? PMID- 11765523 TI - Endodontic decisions based on clinical appearance. AB - Too often, endodontically compromised teeth are ignored because they are not accurately identified, nor their significance realized. By systematically evaluating each potentially affected tooth, a practitioner can correctly diagnose endodontic cases and plan therapy accordingly. Endodontic pathology, with non vital pulps and subsequent abscessation, can affect not only the tooth but also the rest of the patient. Physical examination, both external and oral, can be combined with tactile and transillumination assessment. Radiographic appraisal is essential in determining periapical health, both to determine the vitality of the tooth and to ascertain if endodontic therapy is appropriate, of if extraction is the best choice. This report aims to provide the reader with a clearer understanding of diagnosing endodontic cases to facilitate selection of the appropriate treatment. PMID- 11765524 TI - Endodontic instruments for root canal therapy. AB - This article on endodontic instrumentation includes endodontic instruments and techniques of root-canal preparation of teeth in veterinary patients. Familiarity with instruments covered in this article and with advances in veterinary endodontics has become necessary for the veterinary dental practitioner who wishes to practice dentistry using current techniques. Veterinary endodontic techniques that help to retain the teeth longer are increasing in demand as an option to extracting damaged teeth. Endodontic treatment involves removal of the irreversibly damaged pulp, followed by cleaning and shaping of the root canal space using endodontic instruments and subsequent filling, or obturation, with a semisolid material and a sealer. PMID- 11765525 TI - Restorative procedures after root canal therapy. AB - One of the most common indications for veterinary dental restoration involves replacing tooth structure after a root canal procedure. Special considerations are necessary due to the interaction of the restorative material with materials used to obturate the root canal. The restoration must provide a hermetic seal of the pulp chamber, as well as restore function. Combining several different restorative materials provides the best overall performance. In certain instances, full crown coverage is required to restore functional length or cervical anatomy. PMID- 11765526 TI - Gutta percha obturation techniques. PMID- 11765527 TI - Endodontic treatment of vital pulp tissue. PMID- 11765528 TI - Endodontic complications. PMID- 11765529 TI - Endodontic decisions based on radiographic appearance. AB - Endodontic disease or disease that affects the internal portion of the tooth is a frequently encountered oral problem of the cat and dog. There are many etiologies that can cause the tooth's health and longevity to be adversely affected. Trauma, tooth malformations of either congenital or acquired origin, and bacterial periodontal ascending infections all can lead to pulpal inflammation, necrosis, and tooth death. One must correlate history, physical exam and radiographic impressions of the tooth, and its supporting structures and adjacent teeth in determining proper treatment options and aftercare. Based on extent, timing, and involvement of adjacent structures, resulting pathology of the tooth may be endodontically treated with either a vital pulpectomy, standard root-canal therapy, surgical root-canal therapy, or when the disease is too extensive by extraction. Through a case presentation, we will discuss some of the decisions that enter into the therapy used to treat presenting pathology. It is the authors' intent to present a thought process for deriving a treatment plan to promote healing. There are many ways to achieve this healing, and therefore, there is no right or wrong plan, but rather one that is based on all the presenting factors. PMID- 11765530 TI - Rotary instrumentation. PMID- 11765531 TI - Surgical endodontics. PMID- 11765532 TI - [Preoperative arterial embolization of intralobar lung sequestration]. AB - A case of a 43-year-old patient with recurrent pulmonary infections due to pulmonary sequestration is presented. MR-angiography revealed an aberrant artery originating from the abdominal aorta feeding the intralobar pulmonary sequestration. Platinum coil embolization of the aberrant artery was performed preoperatively to allow safe surgical resection on the following day. To our knowledge this is the first case in the literature in which elective coil embolization has been performed before resection of lung sequestration. PMID- 11765533 TI - [Abnormality of the spine]. PMID- 11765534 TI - [Radiological diagnosis of bone tumors. 2]. PMID- 11765535 TI - [Spinal arteriovenous malformations]. AB - The vascular malformations of the spine and spinal cord are rare diseases. Possible symptoms may consist in a transient neurological deficit, a progressive sensorimotor transverse lesion or an acute para- or tetraplegia. Damage to the spinal cord occurs by bleeding, space-occupying effects and venous congestion, rarely by steal effects. Classification of the true inborn malformations differentiates between arteriovenous malformations (AVMs), cavernomas and capillary teleangiectasias. The more frequent spinal dural arteriovenous fistula (SDAVF) of the elderly patient is a probably acquired lesion which is presented in a separate paper. Capillary teleangiectasias are mostly incidental findings but may cause differential diagnostic problems. Cavernomas are important causes of hemorrhage and may initially be obscured within the bleeding. MRI is the most relevant imaging procedure in the early diagnostic workup. In case of an AVM selective spinal angiography is required to define the type of the lesion and to decide about the appropriate therapy which may be endovascular-interventional, neurosurgical, combined or attentive. PMID- 11765536 TI - [Spinal dural arteriovenous fistulas]. AB - The spinal dural arteriovenous fistula (SDAVF) is an important cause of a slowly progressive sensorimotor transverse lesion in mostly elderly patients. The disease affects men in 80% of the cases. Per year and per 1 Million inhabitants only 5-10 new cases of the disease have to be expected. Although rare, the serious disease should not be missed. Diagnosis can be made by MRI and spinal angiography. The result of treatment depends on early diagnosis. The arteriovenous shunt is located within the dural layer of the spinal canal. It connects branches of a radiculomeningeal artery with the veins of the spinal cord. Spinal cord supplying vessels are not primarily involved. Arterialisation of the venous part of the spinal cord circulation results in a chronic congestive myelopathy, which can well be demonstrated by MR imaging. The role of selectice spinal angiography is to detect and exactly localize the site of the avshunt, which is rather difficult in some cases. Therapeutic alternatives are effective embolization of the fistula with liquid agents or surgical disconnection. PMID- 11765537 TI - [Spinal angiography: vascular anatomy, technique and indications]. AB - The indication for spinal angiography has to be closely set as in case of inadequate handling this procedure bares the risk of paraplegia. In unclear spinal symptoms lasting over a longer period of time, spinal vascular malformation have to be considered. Spinal vascular malformations are often reversible, especially if diagnosed early. Diagnostic methods have to include spinal angiography if other non-invasive methods do not lead to results. The main point is to consider spinal vascular malformations in unclear cases. PMID- 11765538 TI - [Inflammatory diseases of the spinal cord]. AB - Myelitis is defined as inflammatory disease of the spinal cord irrespective of the underlying aetiology or pathologic-anatomic alterations. It can be caused by direct infections, postinfectious or postvaccinal immunological processes or other (auto)immunological diseases such as multiple sclerosis or systemic vasculitis. The clinical presentation is diverse and varies from temporary sensory deficits to persistent tetraplegia with respiratory insufficiency. Diagnostic work-up must include a thorough anamnesis, clinical-neurological examination, neurophysiological studies, analysis of blood and cerebospinal fluid and neuroradiological investigations. Most important is the spinal MRI: small lesions as well as large lesions throughout the extent of the cord with accompanying edema can be identified reliably. Furthermore, neuroradiological examination can proof or rule out important differential diagnoses. In particular in acute transverse myelitis a quick diagnostic work-up with a spinal MRI is indispensible in order to start an appropriate therapy as soon as possible. PMID- 11765539 TI - [Diagnostic methods in spinal infections]. AB - A targeted successful treatment of spinal infectious diseases requires clinical and laboratory data that are completed by the contribution of imaging procedures. Neuroimaging only provides essential informations on the correct topography, localisation, acuity and differential diagnosis of spinal infectious lesions. MRI with its sensitivity concerning soft tissue lesions is a useful tool in detecting infectious alterations of spinal bone marrow, intervertebral disks, leptomeninges and the spinal cord itself. Crucial imaging patterns of typical spinal infections are displayed and illustrated by clinical case studies. We present pyogenic, granulomatous and postoperative variants of spondylodicitis, spinal epidural abscess, spinal meningitis and spinal cord infections. The importance of intravenous contrastmedia application is pointed out. PMID- 11765540 TI - [Lumbar arachnoiditis as differential chronic spinal symptoms diagnosis]. AB - Lumbar epiduro-arachnoiditis is an infectious disease of the three mengial layers. It is often caused by surgical interventions on the spine. In this survey etiologic factors, clinical symptoms and radiological findings are compared. The radiologic classification of Delamater is described by three clinical cases. The diagnostic value of different procedures such as myelography, postmyelographic computed tomography and MR imaging is evaluated. PMID- 11765541 TI - [Fusion of MRI, fMRI and intraoperative MRI data. Methods and clinical significance exemplified by neurosurgical interventions]. AB - The aim of this work was to realize and clinically evaluate an image fusion platform for the integration of preoperative MRI and fMRI data into the intraoperative images of an interventional MRI system with a focus on neurosurgical procedures. A vertically open 0.5 T MRI scanner was equipped with a dedicated navigation system enabling the registration of additional imaging modalities (MRI, fMRI, CT) with the intraoperatively acquired data sets. These merged image data served as the basis for interventional planning and multimodal navigation. So far, the system has been used in 70 neurosurgical interventions (13 of which involved image data fusion--requiring 15 minutes extra time). The augmented navigation system is characterized by a higher frame rate and a higher image quality as compared to the system-integrated navigation based on continuously acquired (near) real time images. Patient movement and tissue shifts can be immediately detected by monitoring the morphological differences between both navigation scenes. The multimodal image fusion allowed a refined navigation planning especially for the resection of deeply seated brain lesions or pathologies close to eloquent areas. Augmented intraoperative orientation and instrument guidance improve the safety and accuracy of neurosurgical interventions. PMID- 11765542 TI - [Editorial reflections on publications in Spanish]. PMID- 11765543 TI - [Surgery of renoureteral lithiasis. Current indications]. AB - INTRODUCTION: Today, the issue about kidney and ureteral stone and their management is based on ESWL (Extracorporeal Shock Wave Lithotripsy) like singly or as a part of combination therapy. In some cases, endoscopic procedures (URS, PNL) with contact lithotripsy, is the first-line treatment. Retroperitoneoscopic is a therapeutical option in some hospitals. Open stone surgery is now drastically reducing and the endoscopic and extracorporeal methods are increasing, overcoat ESWL in those hospitals who has an own lithotripter. The optimal results of non-invasive procedures, and the ESWL advantages for the patients (outpatient and anesthesia-free treatment, decreased morbidity,...), has caused limited annual indications of open surgery for stone disease even a complete disappearance in many center. MATERIALS AND METHODS: The Stone and Lithotripsy Unit of "Jimenez Diaz" Foundation (FJD) (Madrid), who has an own lithotipter (Modulith SL 20, STORZ) make an evaluation of 54 patients treated with open surgery (1990-2000) in order to reflect on the indications. Nephrectomy for serious paremquimal lithiasic lesions (complicated pyelonefhritis, xantogranulomatosis....) is not included. RESULTS: The open surgery techniques for stone diseases were the classic according to every case: pielolithotomy (simple or extended +/- infundibulolithotomy), anatrophic nephrotomy, ureterolithotomy,.... At the same time it should be resolved those anomalous structures or obstruction associated to the stone disease (congenital hydroneprosis, ureterocele,...). DISCUSSION: Now days are difficult cases of stone diseases to be managed for any methods included open surgery. It's the renal complex stone. Of course, surgery is the best option, the more effectively choice. When endoscopic procedures (URS, NPL) fall and the stone is synthomatic must be operated. When they are serious situation (septic shock, complications derived from the others methods,...). It's necessary an urgent and effectively treatment and it's the open surgery. CONCLUSION: Open surgery is actually indicated for the complex renal stone and the complicated ureteral stone. So, the training on open surgery should be at the same time on the endoscopic, laparoscopic or extracorporeal. Open surgery will be the first-line treatment in some case. Open surgery should be considered in those urgent situation and will be done with skill and precision. PMID- 11765544 TI - [The Burch technique in the surgical treatment of stress urinary incontinence in women. Assessment of results and analysis of failure causes]. AB - OBJECTIVE: To present our experience with the Burch procedure in the treatment of female urinary stress incontinence (USI) and the assessment of the causes of failure with this technique. MATERIAL AND METHODS: From January 1987 to june 1997 this technique was applied to 157 patients with USI. The mean age of these women was 54.2 years (30-76) and the mean follow-up was 50.24 months. Physical examination, urethral profile and the severity of the USI were not considered in the indication of the procedure. RESULTS: After three months, we had total continence or improvement in 80.7%. This rate decreased to 76% after one year. From the second year it was 70%, maintained to fifth year. Considering the severity of incontinence, in patients with mild-moderate grade, we obtained good outcomes after 5 years in 87%. If there was associated detrusor alterations, the rate decreased to 51.8%, and with a bad urethral profile, decreased to 42.4%. CONCLUSIONS: The Burch procedure is useful in the treatment of USI but requires a good selection of the patients. PMID- 11765545 TI - [Crude rate increase of prostate cancer incidence in our setting]. AB - The prostate cancer is one of the most frequent cancers in the male sex and its incidence is increasing progresively in a population that every time has a more increased age. OBJECTIVE: To know the crude rate of prostate cancer in our population and if there is an increase. MATERIAL AND METHODS: Knowing the number of habitants under our assistance, we analyze the cases diagnosed of prostate cancer. RESULTS: The crude rate of the incidence of prostate cancer in our medium is 28.7 cases/100.000 habitants/year and this increases progressively in 3 cases/100.000 habitants/year. CONCLUSIONS: There is an increase of the crude rate of the incidence of prostate cancer probably by the influence of the increase of the population's age and the generalization of the measure of PSA in simtomatic patients of prostatic disease. PMID- 11765546 TI - [Urologic complications in renal transplantation. Study of 250 cases]. AB - OBJECTIVE: The aim of this study is value the incidence of urological complications (fistulae and estenosis) in our serie of renal transplant, to analyze the variables that can influence in their appearance and the treatments used. Likewise, to value the follow-up of theses patients and the survival of the renal graft and of the patient. MATERIAL AND METHODS: 250 renal transplants are carried out between july of 1985 and october of 1998. The relationship among the variables you makes by means of the test chi 2 of Pearson and the test of Fisher; the contrasts of stockings with the t of Student; the survival of the organ and of the patient, by means of the analysis of curved of survival according to the method of Kaplan and Meier; and the comparison among curved of survival was carried out with the test of Cloth and Cox. RESULTS: Of the 250 transplants, 46 patients suffered for complications, 29 urinary fistulae (11.6%) and 21 estenosis (8.4%). The most frequent localization in both complications was the union uretero-vesical. The presence of urinary fistulae didn't influence negatively in a significant way nor over the survival of the implant (p < 0.211), neither over the patient's survival. The estenosis appearance was related in a significant way with the donor's age (p < 0.02). The estenosis presence was not related in a significant way neither with the survival of the implant neither with that of the receiver. CONCLUSIONS: The incidence of urological complications was of 18.4% (11.6% estenosis and 8.4% fistulae). The most frequent localization was the union uretero-vesical. The presence of estenosis correlated with the increase of the age of the donors. The technique of reimplante ureteral didn't influence in the results in a significant way. We don't find any relationship between the appearance of urological complications and the patient's survival. PMID- 11765547 TI - [Effect of antibiotic treatment on PSA and percentage of free PSA in patients with biochemical criteria of prostatic biopsy]. AB - INTRODUCTION: PSA serum level measurement in the most important tool in the early diagnosis of prostate cancer patients. However, it is recognised it low specificity is due mainly to prostatic benign diseases. Although it is known that inflammation can contribute on this lack of specificity, there is disagreement in the effect of no symptomatic prostatic inflammatory focus on total PSA and percent free PSA serum levels. AIM: To analyse the biological variability in total PSA and percent free PSA serum levels in patients with biochemical criteria of prostatic biopsy and to compare them with the antibiotic induced variability in a previous urinary infections cohort patients. PATIENTS AND METHODS: We analysed 60 patients with previous urinary infections, normal digital rectal examination and PSA between 4 and 20 ng/ml. We measured total PSA and percent free PSA serum levels. Thirty were treated with 3 weeks of ofloxacin and following a new marker determination. Sextant ultrasound guided prostatic biopsy was performed in all cases. RESULTS: 45 patients demonstrated BPH (29 with prostatitis) and 15 prostate cancer (T1c). Significant variations were found on total PSA serum levels (6.97 ng/ml vs 5.82 ng/ml, p = 0.001) and percent free PSA (14.73% vs 17.77%, p = 0.01) only in treated patients. These differences were significant in BPH and BPH with prostatitis patients but not in prostate cancer patients. Treated patients trend was to decrease PSA (13 treated patients shown PSA < 4 ng/ml vs 2 control patients) and to increase percent free PSA. The median variation of percent free PSA was higher than total PSA and was not influenced by PSA level or prostatic volume. Taking 25 as cut-off of percent free PSA, 18.3% of prostatic biopsies could be avoided in the first determination and 20% in the second. Adding the total PSA reduction, 56% of prostates biopsies in the treated patients could be avoided. CONCLUSIONS: Biochemical criteria of prostatic biopsy could be modified in patients with previous urinary infections due to higher variations on serum markers than those explained by biological variations. These variations could be induced by the antibiotic treatment. These results suggested that the inflammatory focus could influence on total PSA and percent free PSA serum levels. PMID- 11765548 TI - [Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma]. AB - OBJECTIVE: To determine if the morphologic subgrouping of grade I bladder tumors between papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical and survival value. MATERIAL AND METHODS: All 257 consecutive patients diagnosed of superficial bladder cancer between 1990 and 1995 in HU Reina Sofia of Cordoba were reviewed and further reclassified according to WHO/ISUP consensus classification of urothelial neoplasms of the bladder. Of the tumors 12 were urothelial papilloma, 51 were papillary neoplasm of low malignant potential, 43 were low grade papillary carcinoma Ta, 65 were low grade papillary carcinoma T1 and 37 were high grade papillary carcinoma. Eleven patients were reevaluated as T2 tumors and 38 (14.8%) were lost of control. All patients were reviewed with a follow-up at least of 5 years. We compare the results between groups with Fisher test and the risk factors for recurrence and progression are analyzed by multivariate analysis (Odds ratio). The survival function was calculated using Kaplan-Meier estimates and compared with the log rank test. RESULTS: There are no differences between groups respect the age or sex distribution. The differences in the multiplicity are not significant and only the mean size is higher in papillary low grade carcinoma. About the risk factors for recurrence and progression of the disease, only is significative the tumor size. Rarely, the use of chemotherapy seems to play a role in the recurrence. There are no differences in recurrence and progression between the groups, although the percentages are always higher in the papillary low grade carcinoma group. CONCLUSIONS: There are enough clinical differences between the two groups and we consider them as distinct pathologic entities. Only the higher tumoral size is prognostic factor in each group. We think that the use of chemotherapy must be avoided in this low grade bladder tumors. PMID- 11765549 TI - [Usefulness of free/total PSA ratio and PSA density in distinguishing benign prostatic hypertrophy from prostatic cancer]. AB - OBJECTIVE: To investigate the clinical significance of the free-to-total prostate specific antigen ratio (f/tPSA) and PSA density (PSAD) for prostate cancer detection in patients with intermediate tPSA levels (4-10 ng/ml). To establish a cutoff to discriminate between benign prostatic disease (BPH) and prostate cancer (CaP), avoiding unnecessary biopsies. METHODS: This prospective study included 136 men, aged between 54 and 85 (mean 70.6) years old. Urinary tract symptoms were present in these patients. Serum samples were obtained to measure tPSA, fPSA, and f/tPSA; digital rectal examination and transrectal ultrasound eight sector biopsies were performed. Prostate volume was measured and PSAD calculated. The pathologic study, carried out in 113 patients, showed 82 with BPH and 31 with prostate cancer in various stages. RESULTS: There were no significant differences between patients with BPH and CaP when comparing tPSA, fPSA, f/tPSA or digital rectal examination. PSAD and prostate volume were significantly different in patients with BPH and CaP. With a sensitivity of 94% (78.5-99), the f/tPSA cutoff was 0.28 with a 11% (5.2-19.8) specificity. With a sensitivity of 96.2% (80.3 99.4) cutoff for PSAD was 0.109 and specificity 25% (15.5-36.6). CONCLUSIONS: In patients whose tPSA level is between 4 and 10 ng/ml, f/tPSA has no advantages over tPSA measurement for early detection of prostate cancer. DPSA can improve specificities, without compromising the detection of CaP. PMID- 11765550 TI - [Contrast-free helical computerized tomography compared with ultrasonography and simple abdominal radiography in the study of patients with acute lumbar pain]. AB - OBJECTIVE: Evaluation the diagnostic ability of unenhanced helical computed tomography in the evaluation of patients with acute flank pain. PATIENTS AND METHODS: Prospectively evaluation of 82 patients referred for acute flank pain between january 1999 and june 2000. 78 patients were imaged with, 73 abdominal ultrasound and 46 with TCHNC. RESULTS: Plain radiography shows 49.1% of diagnosed lithiasis. Ultrasound was 48% sensitive and 96% specific. TCHNC was 100% sensitive and 84% specific in the diagnosis of lithiasis, allowing in 11 patients a diagnosis unrelated to stone disease. CONCLUSIONS: TCHNC is a valuable radiologic technique for patients presenting with acute flank pain and consider the TCHNC as initial evaluation technique in patients with acute flank pain, allowing not only the localization of the stone as well as the diagnosis of extraurinary pathologies. PMID- 11765551 TI - [Bladder leiomyoma]. AB - A new case of leiomyoma of the bladder is presented in a patient with unspecific symptoms and the preoperatives patterns don't give to a certainty diagnosis. The conclusive diagnosis was obtained with pathoanatomical study of the quirurgic piece. PMID- 11765552 TI - [Malignant vesico-prostatic fibrous histiocytoma]. AB - Among the adult bladder sarcomas it's extremely rare as an histological variety the malignant fibrous histiocytoma. We present a case of a 25 years old young male with bladder and prostate both affected, successfully treated with radical surgery and poliquimiotherapy. We also reviewed the bibliography about this neoplasias up to now. PMID- 11765553 TI - [Hematuria secondary to arterioureteral fistula. Endovascular treatment]. AB - Presentation of case of patient with macroscopic anemic hematuria caused for the presence of a fistula between the external iliac artery and the ureter. After the diagnosis, a treatment with endovascular mangement was made. The arterioureteral fistulae are a very rare entie, which supposes a vital emergency. The diagnosis depend upon the clinical evidences (complementary explorations rarely provide specific findings). Classic treatment is bases on open surgery, while endovascular treatment may be an alternative with less aggressiveness. PMID- 11765554 TI - [Giant retroperitoneal hemangiopericytoma]. AB - We present a new case of retroperitoneal hemangiopericytoma with the special feature of a big size tumour. Due to this feature and also to the hypervascularitation we proceeded a preoperative arterial embolization that made possible its complete removal. We did a bibliographic review showing the fundamental clinic pathologic and therapeutical basic aspects of this tumours. PMID- 11765555 TI - [Neuroendocrine renal tumor. An unusual case. Review of the literature]. AB - The neuroendocrine renal tumors are of extremely strange presentation. We present a review of the literature published on this pathology. PMID- 11765556 TI - [Bone metastasis secondary to renal carcinoma diagnosed with bone scintigraphy]. AB - We reported the case of a 35-y-old man with renal cell carcinoma and cold lesions detected by bone scintigraphy, related to metastatic involvement. Conventional X Ray did not show any pathological findings, being confirmed by axial computed tomography (CT) the scintigraphic bone lesions. We have accomplished a discussion of the role of bone scintigraphy and complementary techniques (radiography, alkaline phosphatase levels) in the diagnosis of bone metastases in renal cell carcinoma. PMID- 11765557 TI - [Iliac pseudoaneurysm in non-functioning renal graft 10 years after embolization]. AB - The arterial pseudoaneurysms are an infrequent complication or renal transplantation. Depending on her localization, are divided in intra and extrarenal. The first are relacionated with the practice of percutaneous needly biopsy. The seconds are associated with defects of vascular anastomose or infection onsurgical area (with relative precocious presentation). Presentation of case of a iliac pseudoaneurysm in non-functional kidney allograft embolizated ten years before. This pathology, for this clinic gravity, requires urgent surgical treatment. PMID- 11765558 TI - [Comments on "Renal oncocytoma: unusual presentation form]. PMID- 11765559 TI - [Quality in the health care system]. PMID- 11765560 TI - [Four models for external quality assessment in the health sector]. AB - European hospitals have adopted four different models for external assessment of their quality systems: Accreditation along the JCAHO criteria Certification along the ISO 9000 criteria Assessment according to the EFQM model Visitatie (in Netherlands). The characteristic of the first three models are exposed, and their differences and similarities discussed. The perspectives for the future in Switzerland are briefly presented. PMID- 11765561 TI - [Risk management in the hospital milieu: needs and implications]. AB - Medicine can be dangerous for the patients, the caregivers, the visitors and the environment. Technological progress provides devices and drugs that are always more powerful, more efficacious, but at the same time able to lead to severe side effects. This paper describes the system set up in a university hospital to fulfill legal requirements. Specialists in specific fields build up commissions, which are united in a coordination office. A general policy for the hospital has been decided, but each commission is responsible for managing the risks in its field. The overall philosophy moved from a quality assurance to a quality management system, in which the employee involved in an incident or an accident is no longer considered the only culprit except in cases of obvious violation of established procedures. In order to be efficient, the system must be as simple as possible, and well known, so that collaborators gain confidence in it. Once this cultural revolution is accomplished, quality but also security of the procedures will be improved. Its impact on cost is more questionable, as the system generates running costs which might be higher than the savings it might bring. PMID- 11765562 TI - [Quality indicators pertinence and limits in medicine: example of nosocomial infections]. AB - Insuring that quality indicators really measure quality of care and not other factors, such as the type of intervention or the patients' characteristics, is notoriously difficult. In order to avoid as much as possible these potential methodological pitfalls, the association FoQual (www.hospvd.ch/quality/foqual) requested in the year 2000 the opinion of experts on the scientific value of some indicators, considered for introduction into practice by the commission on quality of care representing the Swiss hospital association and the health insurers' association (H+/CAMS), as well as on theoretical and practical aspects essential to guarantee their efficiency. The expert group Swiss-NOSO (www.hospvd.ch/swiss-noso) was asked to assess the indicator "nosocomial infection". This example illustrates some pitfalls to avoid, the importance of including infectious surveillance into a global prevention program and ask professionals with a specific training and independence from hospital wards to perform this activity. It shows the complexity of setting up and exploiting quality indicators in health care and the side effects that they might have. PMID- 11765563 TI - [Quality management at the University Hospital and Orthopedic Hospital of French speaking Switzerland: coherence in diversity]. AB - All hospitals in Switzerland will have to set up and run a quality management system, according to legal and contract requirements. However, their context and characteristics are quite different, and will have an impact on the type of system they will select and implement. The University Hospital in Lausanne and the Hopital Orthopedique de la Suisse Romande are neighbour hospitals, which run an orthopaedic ward on both locations. Despite their different sizes, they need a common philosophy and collaboration to set up and run their quality management system. The different stages, strengths and difficulties of both projects are described and compared. The illustrate how coherent the two projects can be despite their initial diversity. PMID- 11765564 TI - [Quality management in rehabilitation centers: evaluation of an experience with two reference generations]. AB - The Agency for the Promotion and Evaluation of Quality in Healthcare and Social Institutions (APEQ) has issued the second generation of quality referentials for readaptation centers. This article summarises the history of the system and presents some characteristics and experiences linked to these two generations of referentials. PMID- 11765565 TI - [The Balanced Scorecard: quality management in aide associations/foundations and home care services]. AB - In order to improve and defend quality of care, the foundation for help and home care in the canton de Vaud called upon modern instruments and methods of management, which proved their value in managing quality and innovation in world famous firms. The Balanced Scorecard developed by Kaplan and Norton belongs to these tools. This article summarise the setting up of this instrument by a non profit organisation in health care, and illustrates its benefits and limits. Despite the absence of objective proofs of added value brought upon by the Balanced Scorecard, the first signs of a major mentality change can be detected, in which the client becomes the central part of the mission of the organisation. PMID- 11765566 TI - [Quality in ambulatory medicine]. AB - The perspectives of the insurance companies, medical associations and practitioners about quality in outpatient care are different. After a brief discussion of each of these views, a proposal for quality improvement through continuous medical education is presented. It applies to the doctor-patient relationship, the diagnostic and therapeutic strategies and the handling of uncertainty. Practically, simulations can help the physicians to understand the theory behind continuous quality improvement and apply it to the process of outpatient care. PMID- 11765568 TI - [Cost benefit aspects of quality: is there a return on the investment?]. AB - Quality health care has a cost with three components: the cost of the diagnostic or therapeutic procedure itself, the cost of error or side effects prevention, and the cost of error or side effects treatment. Hence an optimal position must be found. The literature shows that quality projects aiming at decreasing the cost of side effects treatment usually lead to savings. On the other hand, legal or contract requirements aiming at preventing side effects from happening usually lead to additional costs. Therefore, specific assessment methods to compute the costs and benefits of quality programs must be developed. It would be paradoxical to waste resources in setting up and running a quality assurance program. PMID- 11765567 TI - [Can we still guarantee the quality of care?]. AB - Quality of care in the patients view is different from that of health care providers. It must be taken into account as well. The Swiss Patient Organisation has twenty years of experience in this field. Three aspects of quality of care are specifically presented: health care providers competence, patient information and the constructive use of medical errors happening in hospitals. The organisation has stated that the will for improving quality is widely spread among health care providers. However, quality improvement has a price that will have to be faced to put in to action and meet this new challenge in medicine. PMID- 11765569 TI - [Economic evaluation and rationing: is age an adequate criteria?]. AB - Old age is one of the criteria used for priority setting in a context of limited resources and of health care rationing. Rationing on age is supported by the various types of economic analysis. However, economic evaluations have methodological limitations and sometime lead to conclusions that compromise the efficiency objective. In addition, an utilitarist approach is criticized for neglecting the equity objective of the health care system. Age is an imperfect reflect of health status and prognosis at an individual level, which remain difficult to translate into an easily defined criterion for rationing purposes. PMID- 11765570 TI - [Textual analysis of patients' complaints in the hospital milieu]. AB - The text of patient's complaints in a parisian hospital have been examined in order to describe the recurrent types, but also the argumentation's modalities of both sides. We describe the process of answering by showing the different stages in building the answer. A process of enquiry appears, where the answer has to reconstitute the facts and to relate them with the expressed complaint. This process is especially important in the case of medical and informational complaints, domains where the asymmetry between patient and clinician is especially wide. This drives us to show the deficiencies of a purely written complaint-process. To avoid these insufficiencies, the relevant answers and questions have to be involved in a real dialogue, where both sides can equally contribute in reconstructing the information. This confirms the necessity of introducing conciliation commissions in medical structures, where patients could directly express their complaints. PMID- 11765571 TI - [Occupational anamnesis in primary care medicine: presentation of a screening questionnaire for health problems related to work]. AB - A brief screening questionnaire has been administered to 791 patients consulting a primary health care physician, to discover job-related health problems. Among the 791 patients, 43 percent estimate subjectively that their job has an unfavorable influence on their health. The study participants were patients from the general consultation of the outpatient department of the medical universitary policlinic of Lausanne and from 10 private medical practices in the french part of Switzerland. Among the 791 patients, 401 were interviewed seconderly in a more detailed questionnaire. These questionnaires were evaluated by 3 reviewers of the Institute of Occupational Health Sciences. 25 percent (one of four patient) was identified for having a job-related health problem. For the primary health care physician, the question is: how to manage such job-related problems and how to orient patient to use the adequate services and institutions. PMID- 11765572 TI - [Arthroses: futility or challenge--a survey of the actual situation]. PMID- 11765573 TI - [Minimally invasive approaches in neurosurgery]. PMID- 11765574 TI - [Image of the month. Loss of respiratory sinus arrhythmia in diabetic autonomic neuropathy]. PMID- 11765575 TI - [How I treat ... sickle cell anemia: current therapies]. AB - Vaso-occlusive crisis, thromboembolic events and acute chest syndrome are the most frequent complications in patients with sickle cell disease. Appropriate management of the vaso-occlusive painful crisis includes aggressive analgesia and hydratation. For thromboembolic events, anticoagulation and acetylsalicylic acid with dipyridamole may be considered. Transfusion has a place during some crisis, when hemolysis is increased. Hydroxyurea, a drug that induce foetal hemoglobin synthesis until 30%, has a therapeutic benefit in decreasing the number of vaso occlusive episodes, of transfusions and that of the acute chest syndrome. Currently, the only treatment that allows definitive cures is familial allogeneic stem cell transplantation. New agents are currently under clinical evaluation such as NO and arginine for aggressive crisis or other aggressive complications and administration magnesium and clotrimazole to prevent intracellular deshydratation. These drugs block cation-transport channels in erythrocyte membranes. PMID- 11765576 TI - [Clinical case of the month. Whipple's disease: inaugural psychiatric symptoms]. AB - First considered to be a metabolic illness of the gastro-intestinal tract, Whipple's disease has progressively been recognized as a systemic bacterial disorder due to Tropheryma Whippelii and responding to antibiotics. Neurological symptoms occur in 10 to 20% of cases either initially or during the disease course. Involvement of the central nervous system alone is rare. Modern molecular biology methods, i.e. PCR amplification of 16S rRNA can be applied to accessible biological fluids and/or tissue allowing an early diagnosis, which can lead to earlier administration of adequate antibiotics as well as to a more accurate monitoring of disease evolution. We report a patient suffering from Whipple's disease and presenting initially with severe mental and behavioral disturbances which were thought to be due to a psychiatric disorder. PMID- 11765577 TI - [Clinical case of the month. MELAS syndrome]. AB - A patient, born in 1961, was first examined for autoimmune hyperthyroid at the age of 25. Then, several episodes of serious dehydration and alteration of general condition were followed by a severe encephalopathy with a symptomatology of stroke-like episodes, and during a hospitalization, a volvulus of the colon. Epilepsy developed also. A MELAS syndrome was diagnosed when she was 32 years old, based on her clinical metabolic history of the presence of Ragged-Red-Fibers at muscular biopsy and of the genetical analysis. At the age of 37, after a new episode of encephalopathy, the patient fell into a rapidly evolving coma and deces. PMID- 11765578 TI - [Anthrax and carbuncle]. AB - Anthrax is a name given in French language to two distinct infectious diseases. One corresponds to carbuncle which is a collection of boils. The other one corresponds to the English term anthrax. This condition has a clinical presentation and an outcome that vary according to the inoculation site being cutaneous, pulmonary or digestive, and to the bacterial and toxin spread in the body. PMID- 11765579 TI - [Chronic obstructive pulmonary disease (COPD): current concepts]. AB - COPD is a widespread disease in western countries affecting 10% of adults and linked to tobacco consumption in 90% of cases. This disorder is characterized by a reduced maximal expiratory flow which is irreversible and slowly progressive over the years. In those who are genetically prone to develop a COPD, chronic exposure to toxic fumes or particles generates a bronchiolitis and an emphysema which cause disturbances in ventilation mechanics and alveolar gaz exchange. This leads to symptoms of breathlessness, hypoxemia, pulmonary hypertension and, in end stage disease, cor pulmonale. The smoking cessation is the only way to prevent the occurrence of COPD. PMID- 11765580 TI - [Risk of contamination by hepatitis C of endoscopes utilized in gastroenterology hospital service]. AB - Transmission of hepatitis C virus by gastrointestinal endoscopy has been suggested especially therapeutic procedures. The aim of this study was to investigate the frequency of contamination of the endoscopes by hepatitis C virus and to assess the efficacy of a semi-automatic disinfection procedure. METHODS: In 19 patients with chronic replicative hepatitis C, upper gastrointestinal endoscopy with different invasive procedures was performed. Cleaning and disinfection were carried out according to the recommendation of the belgian "Conseil Superieur de l'Hygiene": cleaning with detergent solution, rinsing, disinfection with a disinfectant solution for 10 minutes and again rinsing. Before the procedure (T0), a blood sample was collected to detect the presence of hepatitis C virus RNA. Immediately after the endoscopic procedure, the operating channel of the endoscope was flushed with water and was sterilely collected (T1); after cleaning (T2) and after disinfection (T3, T3EC), the same procedure was repeated. The collected samples were analysed by PCR in order to detect hepatitis C virus RNA. RESULTS: All the samples were positive at T0. Virus C RNA was found in 10 out the 19 patients at T1 (53%). The results were negative in all the samples both after cleaning (T2) and disinfection (T3-T3 EC). CONCLUSIONS: Our study confirmed the presence of hepatitis C virus in the operating channel after invasive upper gastrointestinal endoscopy. The contamination rate of the endoscope is high. Our cleaning and disinfection procedure seems to be effective in regard of hepatitis C virus RNA clearance. PMID- 11765581 TI - [Cutaneous side effects of interferons]. AB - The alpha, beta and gamma recombinant interferons are indicated in a growing spectrum of therapeutic indications. Some unwanted side effects occur on the skin. The main clinical presentations include vesiculo-bullous sometimes infiltrated dermatitis, vasculitis, necrosis, ulceration and alopecia. Exacerbation of dermatoses such as psoriasis is also possible. PMID- 11765582 TI - [Sense of coherence and commitment to a cardiac rehabilitation program after a myocardial infarction: preliminary results]. AB - This study investigate the impact of the sense of coherence or SOC (1) on the commitment to health behaviors, as the participation in a revalidation program (physical training) after a first myocardial infarction. Fifteen subjects have been assessed three times after their myocardial infarction. The data indicate a possible effect of the sense of coherence which is higher among participants in comparison with subjects who refused to be involved in the program. PMID- 11765583 TI - [Current understanding of diabetic retinopathy]. AB - The incidence of diabetes continues to increase and it is estimated that the world diabetic population will have doubled in 2010. Diabetic retinopathy, one of the most frequent and precocious diabetes' complications, is increasing too and it represents a major cause of blindness in industrialized Countries. The purpose of this article is to describe the relations existing between the risk factors and the physiopathology of diabetic retinopathy, which may be helpful in taking therapeutic and prevention decisions, for the management of diabetic patients. PMID- 11765584 TI - [How I explore ... lumbar paraspinal muscle electromyography in the assessment of radiculopathy]. AB - Lumbar paraspinal muscles examination is an interesting part of the electrodiagnostic evaluation of patients with suspected lumbosacral radiculopathy. However, many electromyographers hesitate to routinely include that technique in their study of lower limbs. The purpose of this paper is to specify the anatomy and electrophysiologic data of multifidus lumbar paraspinal muscle. Previous anatomic studies indicate that the medial lumbar multifidus and lumbar interspinalis muscles share unisegmental innervation by the dorsal ram of the spinal nerve. Electromyography of these muscles can improve the sensitivity of lumbosacral radiculopathy detection. Multi-MUP analysis of quantitative electromyographic parameters in lumbar paraspinal muscles, in a population of 75 healthy subjects without back pain, allowed to set up normal values for the L5 myotome. PMID- 11765585 TI - [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials]. AB - Nephropathy associated with type 2 diabetes mellitus is a rising cause of end stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy. PMID- 11765586 TI - [Info-Meeting. Pharmacologic prevention of the progression from impaired glucose tolerance to type 2 diabetes: favorable effects of metformin and acarbose]. AB - We report the positive results of two large prospective studies of pharmacological prevention of type 2 diabetes presented at the EASD Congress in Glasgow, September 12, 2001. In the "Diabetes Prevention Program", metformin (2 x 850 mg/day), a biguanide compound, reduces the progression from impaired glucose tolerance towards type 2 diabetes by 31% (p < 0.001) while in the "STOP-NIDDM trial", acarbose (3 x 100 mg/day), an alpha-glucosidase inhibitor, diminished it by 24% (p < 0.002). These results are, however, less marked than those obtained with lifestyle modifications including better dietary habits and increased physical exercise (-58% versus control group, p < 0.001). PMID- 11765587 TI - Studies of the toxic effects of norepinephrine on isolated cardiomyocytes of guinea-pigs. AB - Catecholamines have been demonstrated to possess direct cardiotoxic effects mediated by oxygen free radicals in isolated organ preparations. In order to assess direct cytotoxic properties, the influence of exogenous noradrenaline (norepinephrine, CAS 51-41-2) (10(-6) mol/l) on isolated guinea-pigs cardiomyocytes was examined, in the presence of propranolol (10(-6) mol/l) and phentolamine (10(-6) mol/l) to inhibit adrenoceptor-mediated effects. Cell viability was assessed by morphologic examination (% of striated, rod-shaped cells), before and after a treatment period of 15 and 60 min by the measurement of intracellular enzyme activities in the supernatant of the suspension (lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase). The proportion of viable, rod-shaped cardiomyocytes (21.6% +/- 7.6% after preparation, before starting the treatments) significantly decreased over the experimental time (p < 0.05) and, concomitantly, the activity of intracellular enzymes in the supernatant increased. There was no difference between controls and treated suspensions. Thus, there is no evidence for direct toxic effects of norepinephrine in micromolar concentration on isolated cardiomyocytes of guinea-pigs. However, cytoprotective effects by propranolol and/or phentolamine cannot be excluded in this model. PMID- 11765588 TI - Synthesis and in vitro studies of pyrone derivatives as scavengers of active oxygen species. AB - The antioxidant properties of eleven alpha-pyrones and four gamma-pyrones were evaluated by means of three different tests: reduction of the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion scavenging assay and lipid peroxidation assay. In the DPPH test, 6-aryl-5,6-dihydro-4-hydroxypyran 2-ones (3) and 4-hydroxypyran-2-one (5f) were the most active derivatives with IC50 values ranging from 36.7 to 394 mumol/l. Potent superoxide anion scavenging properties appeared in derivatives possessing phenol moieties. Thus phenolic pyrones 5e and 5f exhibited a noteworthy activity (IC50 = 0.180 and 0.488 mmol/l, respectively) when reference compound, ascorbic acid, demonstrated only 24% inhibition at a concentration of 1 mg/ml. In addition derivative 5f significantly inhibited the Fe2+/ADP/ascorbate-induced lipid peroxidation of rat liver microsomes with an IC50 value of 0.069 mmol/l. Due to its multiple mechanism of protective action, compound 5f may be useful for the treatment of oxidative tissue injury in human disease. PMID- 11765589 TI - Increased absorption rate of diclofenac from fast acting formulations containing its potassium salt. AB - Diclofenac (CAS 15307-86-5) is a non-steroidal anti-inflammatory drug largely used, mainly to relief pain of various origin. Diclofenac is present on the market as free acid, as sodium salt (CAS 15307-79-6) and as potassium salt (CAS 15307-81-0). The last salification form has shown a prompter absorption rate and a faster onset of analgesic activity than the acid form and sodium salt. This paper extensively reviews three trials carried out on healthy volunteers, where potassium salt of diclofenac present in three fast-acting formulations, namely sachets (Trial 1), tablets (Trial 2) and oral drops (Trial 3), were compared to reference tablet formulations from the market. A very fast absorption rate was encountered with the three test formulations, with the peak reached in one case 5 min and in most cases within 10-15 min after dosing. The quick absorption rate of test formulations was attributed to the special combination of the salt of diclofenac with a dynamic buffering agent, namely bicarbonate, present in the test formulations and covered by an international patent. The prompt absorption of diclofenac from the new fast-acting formulations was accompanied by the presence of only one peak, whereas the reference formulations produced in most cases two peaks, as widely described in literature. This finding suggested the hypothesis that the absorption of test formulations should occur in a shorter tract of the gut. The faster absorption of diclofenac from the three fast-acting formulations is expected to produce a faster onset of analgesic action, which highlights these new formulations as particularly indicated to relief pain of any origin. PMID- 11765590 TI - Effect of lysine clonixinate on the pharmacokinetics and anticoagulant activity of phenprocoumon. AB - The effect of the non-steroidal anti-inflammatory drug lysine clonixinate ([2-(3 chloro-o-toluidino)nicotinic acid]-L-lysinate, CAS 55837-30-4) on the pharmacokinetics and anticoagulant activity of phenprocoumon (4-hydroxy-3-(1 phenylpropyl)-coumarin, CAS 435-97-2) was investigated in an open, randomised, two-fold, cross-over study in 12 healthy male volunteers. These subjects received a single dose of 18 mg phenprocoumon without or with concomitant treatment with lysine clonixinate (125 mg five times a day for 3 days before and 13 days after ingestion of a single dose of phenprocoumon). Pharmacokinetic parameters of phenprocoumon following oral administration were: CL/f: 0.779 +/- 0.157 ml/min, half-life of elimination: 147.2 +/- 19.9 h; free fraction in serum: 0.51 +/- 0.20%. These parameters were not significantly altered by concomitant treatment with lysine clonixinate. Prothrombin time increased from 13.3 +/- 1.3 s (at time 0) to 17.7 +/- 2.7 s following phenprocoumon and from 13.3 +/- 1.2 s to 18.0 +/- 2.2 s following combined administration. Prothrombin time returned to the pretreatment values 240 h after administration of phenprocoumon. The integrated effect (AUEC0-288 h) was identical following both treatments (4.303 +/- 461 and 4.303 +/- 312 s x h for phenprocoumon alone and phenprocoumon with lysine clonixinate, respectively). Thus, lysine clonixinate administered in therapeutic doses does not affect the pharmacokinetics and anticoagulant activity of phenproxoumon. PMID- 11765591 TI - Capsicum pain plaster in chronic non-specific low back pain. AB - Topically applied capsaicin (CAS 404-86-4) induces the release of substance P, a neurotransmitter, from sensory C-fibres. In addition, there is a specific blockade of transport and de-novo synthesis of substance P. As a result, repeated applications of capsaicin bring about a long lasting desensitisation to pain (increase of pain threshold). The desensitising effect is fully reversible. The confirmed pharmacodynamic actions and a number of double-blind clinical studies indicate that local capsicum preparations are very suitable for the treatment of neuropathic pain or musculoskeletal disorders, with or without inflammatory components. In a double-blind, randomised parallel-group study a capsicum plaster was compared with a placebo for 3 weeks in 154 patients with non-specific back pain. Inclusion criteria were a history of back pain for a minimum period of 3 months and a degree of pain of 5 or more on an eleven grade visual analogue scale. The principal target variable consisted of the score of 3 combined pain scales. Secondary efficacy measures were tests of mobility, a disability index (in the context of Arhus low back rating scale) and global assessments by physicians and patients. For patients to be rated as responders their total pain score at the final examination after 3 weeks of treatment had to show a reduction by at least 30% of the baseline value. The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219). The sum of the 3 separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%; p = 0.002). Relatively slight improvements of the impaired mobility and the functional status are explained by the characteristics of the disorder treated. The efficacy ratings by observers and patients was definitely in favour of capsicum. Adverse effects--mostly harmless and resolving spontaneously--were reported by 15 patients in the capsicum group and by 9 in the placebo group. The tolerance ratings by investigators and patients were superior to the placebo product. This, however, partly is due to the local pharmacological actions of the drug. As in comparably positive randomised studies with capsaicin cream in patients with osteoarthritis or fibromyalgia it was shown that a capsicum plaster preparation can also be used to advantage in chronic non specific back pain. PMID- 11765592 TI - Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus xylometazoline nasal spray in nasal congestion. AB - The aim of this study was to compare the decongestant properties and tolerability of the sympathomimetic xylometazoline hydrochloride 0.1% (CAS 1218-35-5, XMZ) and an oral formulation of cetirizine hydrochloride 5 mg and pseudoephedrine hydrochloride 120 mg (CAS 83881-51-0 and 90-82-4, CTZ/PSE; Cirrus). Thirty-six asymptomatic patients suffering from perennial allergic rhinitis from house dust mite were randomized to this open two-period crossover study. Patients received the study medications for four days each. In each period, treatments were taken twice a day. On day 1 in each period, immediately after the first dose of medication, patients were challenged with Dermatophagoides pteronyssinus extract 1 in the Vienna Challenge Chamber for 5 h. Primary efficacy parameters were nasal congestion evaluated by digital analysis of nasal cavity photographs and nasal airflow. Furthermore amounts of nasal secretions, nasal and ocular symptoms were recorded. In addition, 5 independent Ear-Nose-Throat specialists also assessed nasal cavity photographs. Statistical analyses were conducted at the 5% level of significance. Digital analysis of the nasal cavity photographs as well as nasal airflow measurements did not differentiate XMZ from CTZ/PSE. Ratings of the photographs of the nasal cavity emphasized the rapid onset of XMZ. No clinically relevant adverse events were recorded. This rapid onset of action but short-lived effect of topical xylometazoline 0.1% should be balanced against the consistent and prolonged effect of systemic cetirizine/pseudoephedrine combination in the treatment of perennial allergic rhinitis as no significant differences between these 2 medications were noted regarding their decongestant properties. With the exception of nasal obstruction, all subjective symptoms as well as the global condition were significantly better under CTZ/PSE. Amounts of nasal secretions during these sessions were significantly lower with CTZ/PSE. PMID- 11765593 TI - Pharmacokinetics of two oral prednisolone tablet formulations in healthy volunteers. AB - Two prednisolone (CAS 50-24-8) formulations (Prednisolone 50 mg Ferring tablets as the test preparation and tablets of a reference preparation) were investigated in 13 healthy volunteers in order to prove bioequivalence between these preparations. A single oral dose of 50 mg was given using a randomized, two-way cross-over design with a wash-out period of one week. Blood samples for determination of prednisolone plasma concentrations were collected up to 15 h following drug administration. Additionally, in vitro tests were performed with tablets from the same lots to determine dissolution characteristics. Prednisolone concentrations were measured by means of validated HPLC with UV-detection. Maximum concentrations (Cmax) of 1020.9 +/- 57.8 and 1053.3 +/- 55.7 ng/ml were achieved for the test and the reference preparation, respectively. The AUC0 infinity was 212.2 +/- 13.2 micrograms.min/ml (test preparation) and 222.2 +/- 14.3 micrograms.min/ml (reference preparation). The 90% confidence intervals of the test to reference ratios were within the range of 80-125% with 97.8-101.3% for Cmax and 98.1-100.4% for AUC0-infinity. The time to reach maximum plasma concentration (tmax) tended to be lower (-25%) in the test (39.6 +/- 6.4 min) as compared to the reference preparation (52.8 +/- 9.0 min). Interestingly, this difference correlated well with the observation of a more rapid dissolution rate of the test preparation by some 10 min. Both prednisolone formulations were well tolerated. Based on the results obtained in this study, (1) bioequivalence between the test and the reference preparation was clearly demonstrated and (2) a positive correlation between dissolution rate observed in vitro and tmax as measured in vivo was found. PMID- 11765594 TI - Synthesis and evaluation of new triazolobenzothiazole derivatives as potential anti-tubercular agents. AB - A series of sulfonamides and S-benzyl derivatives of substituted/unsubstituted S triazolo-(3,4,-b)-benzothiazole-3-thiones were synthesized. These triazolobenzolobenzothiazole derivatives were evaluated for antitubercular activity against H37Rv strain of Mycobacterium tuberculosis. A number of promising compounds have been obtained. PMID- 11765595 TI - Protein kinase A of Leishmania amazonensis as a potential target for methoxy amidine. AB - Cyclic 3',5'-adenosine monophosphate (cAMP) is one of the most important signaling molecules for cell growth and differentiation in several systems including protozoal parasites such as Trypanosoma cruzi and Leishmania species. The most important event during Leishmania developmental cycle is the differentiation of procyclic into metacyclic promastigotes, which is associated with the appearance of pathogenicity. As previously demonstrated Leishmania amazonensis metacyclogenesis is associated with an increase of a protein kinase A activity, and therefore further studies on the activity of this phosphorylating enzyme as a target for chemotherapy were performed. Among several amidine derivatives tested by the authors against trypanosomatids (T. cruzi, T. evansi and L. amazonensis) the most effective compounds was defined as that with a methoxy group as substituent. In this work the inhibitory effect of this derivative on the phosphorylating activity of cAMP-dependent protein kinase (PKA) of promastigotes (containing high amounts of metacyclic forms) and axenic amastigotes of L. amazonensis is demonstrated. Soluble fractions (SF) and enriched membrane fractions (MF) were submitted to anion exchange chromatography in a DEAE-cellulose column and the collected fractions used to evaluate the phosphorylating activity associated with cAMP, in the presence/absence of methoxy amidine and pentamidine (CAS 100-33-4), the latter being used as reference drug. PMID- 11765596 TI - Pharmacokinetics of zidovudine following intravenous bolus administration of a novel niosome preparation devoid of cholesterol. AB - A novel niosome preparation composed of nonionic surfactants, polyglyceryl-3 diisostearate and polysorbate-80, bilayers stabilized by myristyl alcohol instead of cholesterol was developed. Polyglyceryl-3-diisostearate, myristyl alcohol and polysorbate-80 were in 1:2:1 molar ratio in which 85% zidovudine (3'-azido-3' deoxythymidine, azidothymidine, AZT, CAS 30516-87-1) was found to be encapsulated in aqueous core. Pharmacokinetic and tissue distribution studies were conducted on this niosome preparation using rabbits and albino rats, respectively, as animal models. AZT levels in rabbit serum were higher following application of niosomal AZT than with AZT solution. Such levels were maintained for prolonged time. T1/2 increased, clearance became slow and as a result AUC and AUMC increased and consequently MRT increased following niosomal AZT treatment. Tissue distribution studies on albino rats also confirmed higher concentration and slower decline of serum levels of AZT due to niosomal AZT. In addition niosomal AZT escaped uptake by reticuloendothelial tissues (liver, spleen, and kidney). Invitro release of AZT from niosomes was slow, about 20% releasing in 18 h. The prolonged AZT levels in rabbit serum following the treatment with niosomal AZT appear to be due to the combined effect of slow invivo release and avoidance of extravascular distribution. Though this preparation seems to maintain AZT levels in serum for a prolonged time, its therapeutic efficacy cannot be claimed as the present method estimates total AZT in the preparation and not free AZT. Further no specific experiments were conducted to substantiate its therapeutic effect. PMID- 11765597 TI - [The effect of a bacterial immunostimulant (human Enterococcus faecalis bacteria) on the occurrence of relapse in patients with]. AB - The following double-blind, placebo-controlled, multicenter study investigated the influence of a bacterial immunostimulant (Symbioflor 1, cells and autolysate of human Enterococcus faecalis) on the occurrence of relapses in patients with chronic recurrent bronchitis (n = 136; placebo n = 66, verum n = 70) in a 6 months treatment period and a follow-up period of 8 months, compared to placebo. Under verum 39 incidents of relapses were recorded, which was about 60% the number observed among the patients treated with placebo (66 incidents). The verum preparation exhibited superior clinical efficacy compared to placebo (p = 0.001) in the Kaplan-Meier test. This better clinical efficiency of the test preparation was particularly observed during the treatment period, with 12 vs. 27 relapses (p = 0.013), but less during the follow-up observation period, with 27 vs. 39 relapses (p = 0.127). In addition, the time span until occurrence of the first relapse was clearly longer under verum (699 days) than under placebo (334 days) and after the end of the observation period 91% of patients under verum experienced only one relapse compared to 62% in the placebo group (p = 0.01). Severity of relapses under verum was also reduced significantly (chi 2; p = 0.001. Only 4 patients under verum required antibiotic therapy compared to 13 patients under placebo. Verum was equally well tolerated as placebo, with no serious side effects in either group. No changes in laboratory tests--haematology and clinical chemistry--were observed. It can be concluded, that previously demonstrated immunomodifying effects of the test preparation have clinical relevance for the treatment of chronic recurrent bronchitis because not only the number but also the severity of acute relapses could be clearly reduced. This is discussed in view of the current literature. PMID- 11765598 TI - [Quality assurance of data collection and data processing in epidemiologic study data]. AB - Quality assurance of the data generating processes in epidemiologic studies is a prerequisite for the internal validity of study results. This paper presents practical aspects of such a quality assurance system pertaining to the planning, data gathering, data entry and data processing phase of a study. It is concerned with data obtained in the framework of a project rather than with data accumulating continuously in private practices, research institutes or veterinary faculties. During the planning phase of a project, standard operating protocols should be developed that assure a reliable performance of observation, coding and data entry. The data base structure, consisting of tables, input validation rules and queries, should be predefined and well documented. A data safety concept will provide the necessary integrity, physical safety and availability of the data. The paper presents technical solutions to common data processing problems with emphasis on re-coding and relational data base facilities (Microsoft-ACCESS) using a hypothetical study on risk factors for mastitis. PMID- 11765599 TI - [The effect of an oral zinc substitution on some biochemical blood serum parameters in pregnant sheep and their lambs as well as on the birth weights of the lambs]. AB - The aims of this study were to demonstrate the effects of zinc sulphate administration (2 g/week p.o., 2% solution) on zinc, copper, iron, calcium and magnesium levels in blood serum of 20 pregnant Ivesi sheep during the last 2 month of pregnancy, immediately post partum as well as in their newborn lambs. In these 20 lambs, also total serum protein, gamma globulin and birth weight were determined. The control group consisted of 15 pregnant sheep and their 15 lambs housed under the same conditions. Zinc sulphate administered to sheep caused significant increases in their serum levels of zinc as well as in those of their lambs. The lambs of the zinc supplemented group had also slightly higher birth weights (not significant) and significant higher gamma globulin levels, whereas the total protein values was almost identical in both groups. PMID- 11765600 TI - Binding of E. coli isolates from pigs with postweaning diarrhea or edema disease to crude intestinal mucin of a weaned pig. AB - The presence of the fedA (gene coding F18 fimbriae) and genes coding STa and LTI enterotoxins and verotoxin Stx2v was determined in 30 E. coli strains isolated from weaned pigs with postweaning diarrhea (PWD) and edema disease (ED). The fedA gene was detected in 22 strains (73.3%). It was mostly associated with the presence of ST gene determinant (14 from 22 fedA positive strains, 63.6%). Two strains possessed ST/Stx2v or LTI/Stx2v combination of genes for both toxins and two strains were negative for investigated toxin determinants. Among 8 fedA negative strains, five strains without gene determinants for toxins were detected. All 30 E. coli strains were investigated for their binding to crude intestinal mucin of a weaned pig fixed in wells of microtitre plates. Positive mucin binding was observed in most of strains, however, great differences were shown between individual strains. Nineteen strains were classified as strongly adherent, 10 strains as weakly adherent, and only one nonadherent strain was found. Three E. coli strains, selected among the best mucin binders, bound to mucin in a concentration-dependent manner. A high mucin binding by E. coli strains was observed only after their cultivation on blood agar plates. Their cultivation in LB broth or on McConkey agar plates had negative effect on the mucin binding by these strains. The mucin binding is not restricted by the presence of fedA gene because the strains displaying very good binding are found either among fedA positive (1, 602/2, 4/3, 576/6) or fedA negative (DK 6, DK 8) E. coli strains. E. coli strains with the highest mucin binding ability belong to potential ST producents (strains 1, 602/2, 4/3, 6/2, 602/4) while the strains without genes coding toxin production displayed lower binding to mucin substratum with exception of the strains ZV5 and 13. PMID- 11765601 TI - The effects of recombinant LHRH fusion proteins on testicular development and histology in ram lambs. AB - Two recombinant luteinizing hormone releasing hormone (LHRH) fusion proteins were evaluated for their effectiveness in suppression of testicular development and histology by injecting together. Recombinant fusion proteins, ovalbumin-LHRH-7 and thioredoxin-LHRH-7, were generated using recombinant DNA technology and expressed in E. Coli. Eleven ram lambs ranked by age and body weight were randomly assigned to receive either ovalbumin and thioredoxin recombinant protein mixture (control group, n = 5) or ovalbumin-LHRH-7 and thioredoxin-LHRH-7 recombinant fusion protein mixture, anti-LHRH vaccine, (immunization group, n = 6). Animals in each group were weaned at 17 wk of age and were injected (primary immunization) with either mixture at 18 wk of age. Both groups received a booster immunization 8 wks later (26 wk of age). Scrotal circumference, scrotal length, testicular diameter and testicular length were measured in both groups every other week. All animals were slaughtered at 36 wk of age. Immediately after slaughter, a small testicular tissue was taken and processed for histological examination. In the ram lambs in immunization group scrotal circumference and testicular diameter increased steadily until second booster and then remained as a plateau until the end of the experiment. The differences in scrotal circumferences and testicular diameter were significant between the two groups during the last three weeks of the study (p < 0.05). There were no differences in testicular and scrotal length throughout the study (p > 0.05). Seminiferous tubules lost their regular shape and were decreased in diameter in immunization group. Although a few spermatozoa were seen in some tubules, in general, there were atrophy of the seminiferous tubules and loss of spermatogenesis, nevertheless, it seemed that animals in this group were potentially fertile. PMID- 11765602 TI - Isolation and identification of motile Aeromonas species from chicken. AB - In this study a total of 140 broiler carcasses and carcass parts purchased at different supermarkets in Ankara including 50 whole carcass, 30 wing, 30 leg and 30 breast samples were analysed for the presence of motile Aeromonas species. According to analysis findings, motile Aeromonas spp. were isolated from 116 (82.9%) of total 140 samples. The distribution of the isolates were 94%, 86.6%, 80%, 63.3% in broiler carcass, wing, leg and breast samples, respectively. Aeromonas hydrophila was isolated the most prevalent species with 56% the range followed by Aeromonas sobria with 29.3% and Aeromonas caviae with 14.7% from all of the carcass and carcass part samples, respectively. Consequently, it was supposed that, examined broiler carcass and carcass parts have been contaminated to important level with motile Aeromonas species and it has been risk for public health. PMID- 11765603 TI - Generalized tuberculosis in a 45 day-old calf. AB - The objectives of the present study were to describe pathomorphological and immunohistochemical features of generalized natural tuberculosis in a 45 day-old female calf. The characteristic lesion of tuberculosis was productive type which was located in the lung, liver, and especially in the lymph nodes (mediastinal, bronchial, mesenterial, portal, prescapular, renal and caudal sternal lymph nodes). Mycobacterium bovis antigens were seen generally in the cytoplasma and around the macrophages, rarely in necrotic areas and Langhans giant cells by avidin-biotin complex peroxidase method. PMID- 11765604 TI - All pumped up. PMID- 11765605 TI - Life's twisted plotline. PMID- 11765606 TI - [Psychogenic neurotic depression in women (psychopathological and psychosomatic aspects)]. AB - Examination of 85 female inpatients with psychogenic neurotic mood disorders aged from 18 to 48 years has found the following depression syndrome variants: asthenic (42 patients), anxiety (14), asthenoanxiety (15), anxiety-melancholic (14). Hypothymia both mildly or moderately expressed and psychosomatic disorders as functional disturbances of reproductive, nervous and cardiovascular systems, were found. These disturbances were qualified as somatoform disorders. The most typical was autonomic dystonia syndrome. During the course of depression, somatization of psychic disorders was increasing, being most distinct in asthenic variants. PMID- 11765607 TI - [The therapy of non-traumatic vegetative state syndrome in children]. AB - Twenty nine non-traumatic appalic syndrome (AS) cases of various etiology were observed in children aged from 3 to 14 years. The clinical picture study was carried out, along with brain structure visualization in vivo (CT and MRT), EEG and cerebral blood flow detection with transcranial ultrasonic dopplerography. All the cases were studied in dynamics in relation to influence of complex course therapy developed by the authors, including vasoactive drugs, nootropics, craniopuncture, acupuncture and electrostimulation of craniopuncture zones. Five patients (17.2%) had a distinct positive dynamics with complete consciousness rehabilitation on the background of moderate neurological deficit regress. In general, CT-data and changes of EEG and cerebral blood flow in AS were not found to have any prognostic value and to be etiologically specific. But changes of EEG and cerebral blood flow in response to the treatment appear to be positive prognostic sign. The prognosis for AS due to meningoencephalitis is worse than one for AS due to hypoxic-ischemic encephalopathy. The non-traumatic AS duration for more than 2 months corresponds to unfavorable outcome. PMID- 11765608 TI - [The pharmacological and hormonal effects of carbamazepine and valproic acid in the treatment of reproductive age women with epilepsy]. AB - Dynamics of steroid hormone (extradiol-17 beta, progesterone, total testosterone and cortisol) concentrations in the middle of follicular and lutein menstrual cycle phases has been studied in women with epilepsy aged 21-30 years. Nineteen patients were treated with valproic acid (depakine--900-2000 mg/day), 35--with carbamazepine (500-1200 mg/day). All the patients have been treated during at least 6 months, paroxysms being not registered during the last 3 months before blood analysis. Control group consisted of 17 healthy age-matched women with no positive familial history of nervous and endocrine diseases. Comparing to the control, the affected groups revealed a significantly lower estradiol level (p < 0.003) during the follicular phase and higher cortisol concentrations during both the follicular and the lutein phases (p < 0.05). Regardless of menstrual cycle phases, the differences in progesterone and total testosterone concentrations have not been found between subgroups treated by carbamazepine and depakine. The same hormonal deviations detected after using both carbamazepine and Depakine in the homogenous subgroups of the patients imply, to a certain extent, a common character of pathogenetic mechanisms for steroid hormone pattern development in women with epilepsy. Carbamazepine and depakine treatment during at least 6 months does not predispose to ovary polycystosis syndrome. The results support a multifactor character of hormonal deviations in epilepsy and do not show the medication factor as a major one. PMID- 11765609 TI - [Efficiency of thioctacid in dyscirculatory encephalopathy]. PMID- 11765610 TI - [Neurophysiological characteristics of transitory global amnesia syndrome]. AB - Twenty seven patients with transitory global amnesia (TGA) in acute and remote (after 7 and more days) stages and 31 dyscircular encephalopathy patients with subjective memory disturbances (control group) have been examined. According to electroencephalographical (EEG) data and wave P300 cognitive evoked potential evaluation, the differences in the beta 1-activity between these groups have been found. beta 1-Activity expression on EEG correlated in different ways with latent P300 periods, increasing together with latent period (r = 0.43) in control group and decreasing in TGA (r = -0.23). The most distinct, changes were expressed in central cerebral regions. The authors hold that the relationship between changes of EEG and cognitive evoked potential in acute and remote TGA stages, as well as in control group, indicate functional character of TGA syndrome, being unrelated to cerebral structure damage. PMID- 11765611 TI - [Neurophysiological criteria for the diagnosis and prognosis of facial nerve neuropathy in children]. AB - Electromyography bindings of blink reflex, visual and acoustic evoked potentials have been studied in 35 children with facial nerve neuropathy (FNN), 20 children with FNN being manifested for the first time and 15 children being affected with recurrent type. Blink reflex analysis in FNN has revealed trifacial and controlateral facial nerve pathology in 10-20% cases. Factors essentional for rehabilitation and development of complications were the following: (1) duration of conduction block along trigeminis-facial nerve arch, (2) conduction block association, according to the blink reflex, with the absence of M-response in direct facial nerve stimulation, (3) a coefficient of M-response amplitude ratio on affected and intact sides, (4) P100 latency disturbance and its wave like rehabilitation during 4-6 months. Recurrent FNN was characterized by: (1) R1 latency increase and ipsilateral R2 in stimulation on intact side, (2) P100 latency fluctuations without returning to normal state, (3) bilateral increase of III peak latency and I-III intervals. PMID- 11765612 TI - [Computed tomography for the diagnosis of the brain damage in infants]. AB - To optimize the diagnosis, a retrospective analysis of cerebral structural changes in newborns and infants with neurological symptoms has been carried out. X-ray computed tomography has been used in 132 newborns and 494 infants, aged from 1 month to 1 year. The study enabled objective diagnosis for conducting an adequate therapy or correcting a treatment. The reasons for computed tomography using in infants have been updated in the study. PMID- 11765613 TI - [Significance of the level of auto-antibodies for the NMDA type glutamate receptors in diagnosis of chronic cerebral circulation disorders]. AB - For studying diagnostic possibilities of a new laboratory test for cerebral ischemia (CIS-test), thirty patients have been examined. The level of autoantibodies to NMDA type glutamate receptors is shown to increase significantly (3-5 times) in patients with stage 2 dyscirculatory encephalopathy. Parallel measurements of free glutamate and homocysteine levels in the patients blood plasma did not reveal any substantial changes of the given parameters, comparing to indices of autoantibodies to NR2a glutamate receptor. The titer of autoantibodies to this receptor type did not change significantly in patients with epilepsy; the titer dependence on dyscirculatory encephalopathy severity level and its decrease during treatment have been found as well. The possibilities of CIS using for diagnosis and therapy control in patients with chronic cerebral circulation disorders are discussed. PMID- 11765614 TI - [Nonspecific cerebral system in catamenial epilepsy]. PMID- 11765615 TI - [Dopamine receptor gene (DRD2) polymorphism in patients with endogenous psychoses with regard to their clinical heterogeneity]. AB - Recently an association between genetic dopamine receptor gene (DRD2) polymorphism and schizophrenia was observed in several studies. In the current investigation we attempted to undertake further study of such association using an extended sample which comprised patients with schizophrenia (n = 184), schizoaffective psychosis (n = 63), affective disorders (n = 121)); healthy control subjects (n = 117) and first-degree relatives of the patients with psychoses who show no signs of mental diseases (n = 111). The genotypes A1A1, A1A2 and A2A2 and the relationship between Taq1DRD2 variants and some clinical symptoms and pathogenetic features of the patients with schizophrenia were studied. The results did not confirm the association between DRD2 genotype and any of disorders studied. But the A2A2 genotype frequency in the schizophrenic patient's group, with illness duration above 20 years and highly expressed positive, negative and psychopathological symptoms, increased significantly as compared to control group (73.7% vs 52.9%) and patients with less illness duration (73.7% vs 42.5%). In the latter case odds ratio was calculated as 4.12. In the light of this finding, A2A2 DRD2 genotype appears to be related to chronicity of schizophrenia. PMID- 11765616 TI - [Neurosurgical treatment for Parkinson disease and other motor disorders]. PMID- 11765617 TI - [Some aspects of spondylo-arthrosis therapy]. PMID- 11765618 TI - [Cavinton in epilepsy treatment and prevention]. PMID- 11765619 TI - [A case of listeriosis with nervous system damage]. PMID- 11765620 TI - [Specific aspects of neurodestructive process and neuroprotective therapy for nervous system disorders]. PMID- 11765621 TI - [On the problem of erotomania]. AB - Ten cases of erotomania with a clinical picture determined by isolated erotic delusion have been examined. Three stages in the disease course (catathymic, delusion systematization and residual) have been recognized. While diagnostic evaluating, an accordance of the disorders with Clerambault's syndrome in disease debut and an increase of erotomanic paranoia symptoms in pathological process development were taken into account. Premorbid personality abnormalities of schizoid spectrum, catathymic character of delusion with affective component in its formation, narrow range and concrete content of persecution ideas, expansive manifestations in the patient behavior and favorable outcome were found to characterize the isolated erotomania. The existence of special marginal types of erotomania, not corresponding to atypical paranoia spectrum (paranoia, paranomic schizophrenia) is assumed. Most of the patients were diagnosed as affected with schizotypic disorder (slow-progredient schizophrenia). PMID- 11765622 TI - DHHS issues guidance to address privacy rule uncertainties. PMID- 11765623 TI - Improving quality of care in cath labs: an ACC initiative. PMID- 11765624 TI - The second phase in creating the cardiac center for the next generation: beyond structure to process improvement. AB - The third generation cardiac institute will build on the successes of the past in structuring the service line, re-organizing to assimilate specialist interests, and re-positioning to expand cardiac services into cardiovascular services. To meet the challenges of an increasingly competitive marketplace and complex delivery system, the focus for this new model will shift away from improved structures, and toward improved processes. This shift will require a sound methodology for statistically measuring and sustaining process changes related to the optimization of cardiovascular care. In recent years, GE Medical Systems has successfully applied Six Sigma methodologies to enable cardiac centers to control key clinical and market development processes through its DMADV, DMAIC and Change Acceleration processes. Data indicates Six Sigma is having a positive impact within organizations across the United States, and when appropriately implemented, this approach can serve as a solid foundation for building the next generation cardiac institute. PMID- 11765625 TI - Practical techniques and perspectives for the cardiovascular administrator. Redefining excellence. PMID- 11765626 TI - A little technology goes a long way. PMID- 11765627 TI - Patient friendly billing: a first step. PMID- 11765628 TI - Terrorist attacks kill congressional healthcare policy agenda. PMID- 11765629 TI - Flasch: provider-owned plan focuses on quality, growth, and new technology. AB - H. Michael Flasch, FHFMA, is vice president of claims/administrative services and support for Detroit, Michigan-based Health Alliance Plan (HAP), a subsidiary of Henry Ford Health System (HFHS), which also comprises a dozen owned or affiliated hospitals, 25 medical centers, and numerous other health services. His responsibilities at HAP encompass benefits coordination, configuration of information services, and the claims function. He also has played a key role in HAP's acquisition and integration of an HMO, SelectCare, in March 2001. Flasch joined HFHS in 1984 as associate controller and senior director of patient financial services. He served as vice president of managed care for HFHS and COO of Alliance Health and Life Insurance Company for HAP from 1995 until 2000, when he assumed his current position. Before Joining HFHS, Flasch worked for Hospital Corporation of America in Nashville, Tennessee, and other hospitals in Cincinnati. PMID- 11765631 TI - Crispin: capital requirements and reinsurance protect against insolvency. AB - Charles Crispin is president of Evergreen Re, a managed care consulting firm with expertise in the reinsurance industry. Before Joining Evergreen Re, Crispin served as a consultant to the managed care industry. He is a member of the American Association of Integrated Delivery Systems, Glen Allen, Virginia, and the Provider Excess Loss Association, Princeton, New Jersey. Crispin recently talked with HFM about risk-based capital requirements for health plans and the Impact these solvency guidelines could have on healthcare providers. PMID- 11765630 TI - The right strategy and perseverance can make an IDS profitable. AB - Results of a recent study of 11 leading integrated delivery systems (IDSs) belie the common perception that IDSs are incapable of turning a profit. The study determined that the primary factors driving the poor financial performance of IDSs are organizational complexity, payment reductions mandated by the Balanced Budget Act of 1997, and a general lack of foresight regarding financial problems when embarking on an integration strategy. By implementing a wide range of initiatives to stem losses and improve financial performance, several of the case study IDSs have accomplished dramatic financial turnarounds over the past three years, and all have achieved consistently stronger financial performance. PMID- 11765632 TI - Improving competitiveness through performance-measurement systems. AB - Parallels exist between the competitive pressures felt by U.S. manufacturers over the past 30 years and those experienced by healthcare providers today. Increasing market deregulation, changing government policies, and growing consumerism have altered the healthcare arena. Responding to similar pressures, manufacturers adopted a strategic orientation driven by customer needs and expectations that led them to achieve high performance levels and surpass their competition. The adoption of integrated performance-measurement systems was instrumental in these firms' success. An integrated performance-measurement model for healthcare organizations can help to blend the organization's strategy with the demands of the contemporary healthcare environment. Performance-measurement systems encourage healthcare organizations to focus on their mission and vision by aligning their strategic objectives and resource-allocation decisions with customer requirements. PMID- 11765633 TI - Preparing for the inpatient rehabilitation PPS. AB - To assess the financial impact of the inpatient rehabilitation prospective payment system (PPS) on its future revenues, the MetroHealth Center for Rehabilitation (MHCR), Cleveland, Ohio, undertook a three-phase process using data from calendar year 2000 to estimate its potential profit or loss for each case-mix group (CMG) identified in the final rule. This process entailed developing a database to facilitate the combination and comparison of patient charge and clinical data by CMG, using the combined data to estimate costs by cost center, and using payment information included in the final rule to estimate revenues by CMG. Following the assessment, the MHCR decided to expand the database to assist clinicians in making informed decisions in their patient assessment and care-delivery processes that would account for cost and revenue considerations under the PPS. PMID- 11765634 TI - Patient friendly billing project: putting the patient first. AB - Freeing the consumer from the confusion of the current billing and payment process is a key long-term goal of the Patient Friendly Billing Project. This project is a joint effort of HFMA and the American Hospital Association, and with support from HCA; Mayo Clinic, Rochester, Minnesota; Northwestern Memorial Hospital, Chicago, Illinois; Quorum Health Resources, Nashville, Tennessee; SSM HealthCare, St. Louis, Missouri; Cap Gemini Ernst & Young; Deloitte & Touche/Deloitte Consulting/Ernst & Young; PricewaterhouseCoopers; Stevens & Lee, Reading, Pennsylvania; Greenwich Hospital, Greenwich, Connecticut; Medical Group Management Association; Centers for Medicare & Medicaid Services; and HFMA's PFS Forum Advisory Council. If the goal of this project is achieved, the healthcare industry can gain from both improved consumer relations and cost-efficient outcomes that benefit all involved. PMID- 11765635 TI - Strategic real-estate planning can generate revenue. AB - Many healthcare organizations treat their real estate as liabilities rather than assets and overlook opportunities to generate significant additional revenue and reduce costs. An Ernst & Young Study found that to maximize the return on investment in their real-estate holdings, healthcare organizations need to include property management in their strategic plan, manage construction and expansion effectively, adapt and reuse their facilities where possible, and pursue innovative real-estate strategies. Managing real-estate assets effectively can free up capital to use for other core business needs. PMID- 11765636 TI - Automated charge capture at the point of care increases revenue. AB - Group practices can reduce lost charges, denied claims, and time-to-billing rates by using automated charge capture at the point of service. One orthopedic department had been experiencing many process-related problems associated with physician charge capture. To improve revenues, the physicians began using hand held devices to input data during patients' office visits. A 12-month analysis of charge data from the orthopedic physicians' outpatient visits using a paper-based charge process showed that 824 outpatient charges had been missed or lost, representing 6 percent of the department's annual outpatient activity and more than $54,000 in projected additional revenue. Another analysis conducted after the automated charge-capture process at the point of care was implemented showed that the orthopedic department had not missed any charges. PMID- 11765637 TI - Medicare+Choice plan withdrawals require providers to be proactive. PMID- 11765638 TI - Proactive CFOs are in demand. PMID- 11765639 TI - E-procurement can reduce expenses. PMID- 11765640 TI - Bigger business, smaller profits. Hospital margins fell in 2000 despite increase in patient visits, the AHA finds. PMID- 11765641 TI - AMA selects new leader. Maves comes from consumer product association. PMID- 11765642 TI - Enough navel-gazing. AMA needs to talk bioterrorism, but lawsuit likely to distract at annual meeting. PMID- 11765643 TI - Simplifying the hospital bill. Task force seeks broad effort to create patient friendly payment process. PMID- 11765644 TI - Signs of life. CHW's fortunes are looking up, but the system isn't out of the woods yet. PMID- 11765645 TI - Full house. After years of decline, inpatient admissions are rising, pushing new construction. PMID- 11765646 TI - Healthy competition. Calif. says discounting drugs is good for business. PMID- 11765647 TI - Survival of the fittest. Docs' hospital, dominant provider both call their specialty the most special. PMID- 11765648 TI - Imaging the future. Independent radiology centers swim circles around hospitals in making high-tech options readily available to patients. PMID- 11765649 TI - A fast track to safety. Children's hospital group seeks proper use of technology to improve care. PMID- 11765650 TI - Helping hand needed. Philly hospitals seek state aid in absorbing huge losses of failed Medicaid HMO. PMID- 11765651 TI - Mixed messages. Just as HHS debuts plan to boost accountability, CMS looks to ease inspections. AB - HHS Secretary Tommy Thompson had good news last week for nursing home advocates, then ran into an ambush. He unveiled a long-anticipated proposal for more public accountability in the industry. The problem was, the public had just found out about possible easing of inspection rules. PMID- 11765652 TI - [HHV-8 infection. Update on pathogenesis and epidemiology]. AB - HHV-8 (Human Herpesvirus 8) is a human lymphotropic and transforming virus closely associated to the development of Kaposis's sarcoma, Castleman's disease and Primary Effusion Lymphoma among immunosuppressed patients. Prevalence of infection varies according to different geographic area and to ethnic group or to risk factors. No effective treatments are available at present. PMID- 11765653 TI - [Cerivastatin. Which lessons for clinical practice?]. AB - The event of cerivastatin is the starting point for several methodological issues that, in the era of evidence-based medicine, should be the scientific basis of clinical practice. The article goes into three main issues: the production of evidence about efficacy of drugs, their safety profile through the collection of data about adverse drug reactions and the appropriateness of drug prescription. PMID- 11765654 TI - [Optoelectronic plethysmography: a new tool in respiratory medicine]. AB - Opto-electronic plethysmography (OEP) is a new noninvasive technique, recently introduced, which is highly accurate in the measurement of total chest wall volume variations, allowing partitioning of the complex shape of the chest wall into different functional compartments. It can measure breathing patterns and, if combined with pressure measurements, can be used to study statics, dynamics and energetics of the respiratory system. OEP does not require connection to the patient and can be used without a subject-specific calibration. All these features and the results obtained in several studies make the OEP not only a reliable system for basic physiological and pathophysiological research studies, but also an attractive tool to be used in clinics. PMID- 11765655 TI - [Economic burden and clinical course of HIV infection and AIDS today: how the variation of natural history, available treatments, and strictly related costs play a role in needs of health care]. AB - In order to provide an updated balance of the evolution of the natural history of HIV infection, the major clinical end-points of disease morbidity and mortality were compared with the progressively increasing use of highly active antiretroviral therapy (HAART), in a cohort of patients followed by our tertiary care centre in an eight-year period including both the pre-HAART and the HAART era. Although direct expenditures for antiretroviral agents reached even 99.8% of overall costs related to drugs and blood derivatives at our entire unit in the year 2000, a clear shift towards outpatient assistance of HIV infection was realized during recent years, leading to an increased and greatly varied spectrum of infectious diseases hospitalized at our inpatient and Day-Hospital units. Due to the significant reduction of inpatient expenditures, even the elevated costs of management of HIV disease based on HAART and periodic virological and immunological monitoring are expected to remain cost-effective, at least during the next few years. PMID- 11765656 TI - [Heart failure and nutritional status in hemodialysis]. AB - Left ventricular function is impaired in long-term maintenance dialysis as a consequence of several inter-related conditions. Aim of the study was to assess if different degree of malnutrition can affect diastolic and systolic function of dialysis patients. Bio-electrical whole-body multifrequency impedance analysis (BIA) allows a dynamic assessment of body composition according to a multi compartment model. This allows an assessment of lean (FFM) and fat mass (FAT), metabolically active cell mass (BCM) and a BIA Nutritional Index (NI). We studied 73 patients (53 M, 20 F), aged 54.41 +/- 3.1 yrs, on maintenance bicarbonate dialysis since 57.3 +/- 61.8 mths, by BIA, performed before and after a dialysis. I-PTH and serum albumin are correlated (r = -0.55, p < 0.001); the same trend is shown by I-PTH vs fat free mass (r = -0.47, p < 0.001) and vs NI (r = -0.51, p < 0.001). Ejection fraction (EF) is correlated with age (r = -0.50, p < 0.001) and with I-PTH (r = -0.59, p < 0.001). Moreover, albumin and EF are closely related (r = 0.36, p < 0.01), as well as EF vs FFM (r = 0.47, p < 0.001), and EF vs NI (r = 0.37, p < 0.01). A/E ratio, assumed as index of left ventricular diastolic function, shows a correlation vs albumin (r = -0.33, p < 0.01), BCM (r = -0.34, p < 0.01) and NI (r = -0.40, p < 0.01), but not with I-PTH. Malnutrition, defined both by BIA measurements and lower serum albumin, could exert unfavourable effects on left ventricular systolic and diastolic function of patients on long term haemodialysis, even independently by hyperparathyroidism. PMID- 11765657 TI - [Cardiac troponin I in chronic hemodialysis. Comparison of methods and results after 3 months]. AB - The laboratory and instrumental markers today in use for the determination of myocardial damage present limitations in dialysis patients due to interference patterns that tend to reduce prognostic evaluation. The aim of this study is to evaluate whether troponin I (cTnI), a recently established marker of myocardial damage, can help to identify, in asymptomatic patients too, minor ischemic lesions that could screen this patient population for future acute cardiac events. In our study of 103 patients undergoing chronic dialysis, instrumental measurements and serum dosages of cTnI were carried out at the onset and after three months, using first and second generation methods. Among the patients who tested positive using the above tests, 4 acute cardiac events were observed. A follow-up of the present study is due in one year's time. PMID- 11765658 TI - [Popliteal (Baker's) cyst in a patient with tubercular arthritis. Report of a case and review of the literature]. AB - The Baker's cyst is a distension of the bursa subtendinea and is caused by noninfectious knee effusion secondary to arthrosis, meniscal tears, trauma, rheumatoid arthritis, gout, or any other form of sinovitis, like rheumatoid arthritis. An infected popliteal cyst is much less common; tuberculous arthritis is exceptional, in fact only four cases are described in literature. Herein we describe an additional tbc case of a 51 years old men, who has been initially treated with cytostatic and corticosteroid agents, for a suspected rheumatoid arthritis. The review of the literature suggests the importance of a correct approach to the diagnosis, based on the analysis and culture of the synovial fluid, because delays latency of effective antibiotic therapy can result in permanent joint damage that invalidate the patients. PMID- 11765659 TI - [Unexpected diagnosis of thorotrast-induced cirrhosis]. AB - It is presented the clinical case of a 73 year old man admitted to hospital with dyspnea and productive cough. Clinico-instrumental investigations demonstrated monolateral pleural effusion and ascites in a severe cirrhotic chronic liver failure. After evacuation of the pleural and peritoneal effusion, chest radiography showed the presence of a double accumulation of radiopaque material in left cervical region and in left paramediastinic site. Chest and abdominal CT scan showed a systemic accumulation of this material in liver, spleen and glands. The characteristics of the iperreflecting substance accumulated were compatible with that of Thorotrast. In the mean time, a prostate cancer with skeletal metastases was diagnosed. Despite therapy, the chronic liver failure causes a rapid deterioration of clinical conditions, with irreversible hepatic coma and death. PMID- 11765660 TI - [Pulse pressure and mean pressure: physiopathology and predictive value of coronary events and ictus]. AB - Increased pulse pressure (PP) reflects an increased stiffness of aorta and other large elastic arteries. These arteries dilate by about 10% during systole and contract owing to elastic return during diastole. As a result, blood flow towards periphery becomes less pulsatile and more continuous. An increased stiffness of aorta and large elastic arteries due to progressively reduced elastic content with aging (atherosclerotic processes) leads to increased systolic blood pressure (BP), because of their reduced distension during systole, and decreased diastolic BP due to their reduced blood content at the beginning of diastole. Several epidemiological studies have shown that PP is the BP component which most closely predicts cardiovascular risk, particularly over 55 years of age. In particular, increased PP is an important predictor of coronary events, while increased mean BP is a more specific predictor of cerebrovascular events. PMID- 11765661 TI - [Prognosis disclosure]. AB - Doctors usually prefer telling the patients diagnosis and therapy than prognosis. Prognostication in fact means foretelling the future, while clinical interventions are scientifical clinical facts. Doctors are accustomed to speak about future only in probabilistic, statistical ways, while the patients ask about their own specific future; so the communication often can become very hard. The prognosis has to do with patient's quality of life, not only with natural history of disease; therefore it is important to establish with the patient a partnership: prognosis must be in fact a common building. A correct prognosis is necessary in informed consent: the outcome of medical intervention must be presented to patients in terms of effects on future quality of life. Prognosis is a very important relational tool: so communication and counselling skills are necessary in medical profession. PMID- 11765662 TI - [Systemic HIV-non-Hodgkin lymphoma in the era of HAART. Natural history]. AB - In the era of highly active antiretroviral therapy (HAART), systemic non-Hodgkin lymphoma (NHL) represented the most frequent cancer associated to HIV infection. In contrast to Kaposi's sarcoma and primary central nervous system lymphoma (PCNSL) which incidence have been declining after introduction of HAART, systemic NHL-HIV has relatively stable remained. Systemic HIV related NHL are markedly heterogeneous both histologically and clinically and this clinicophatological heterogenity reflects variability in the molecular lesions associated to these lymphomas and immunological status of these patients. The introduction of HAART has substantially modified the approach to HIV related lymphomas. The results of recent monoinstitutional study of Aviano Cancer's Institute on 235 patients have suggested that HAART would otherwise allow a long life expectancy with longer disease free survival and overall survival. In fact the reduced of morbidity of AIDS patients bought by HAART justified the use of aggressive antineoplastic therapies. PMID- 11765664 TI - [Non-invasive diagnosis of celiac disease in clinical practice]. AB - Coeliac disease is a permanent intolerance to gluten which requests a quick diagnosis as soon as possible to prevent neoplastic and non-neoplastic complications of the disease, since frequently coeliac disease shows pauci- or asymptomatic forms. We describe herein the most common non invasive diagnostic methods used in clinical practice to diagnose coeliac disease, as well as we describe non invasive methods poorly used or which will play a key role in the non invasive diagnosis of coeliac disease in the future. PMID- 11765663 TI - [Neonatal sepsis]. AB - Sepsis is still one of the most important causes of mortality and morbidity in the neonatal period. Infection is responsible for approximately 2 million neonatal deaths per year in developing countries. In Italy, as in other industrialized countries, the mortality rate has declined to 5.1 per 1000 livebirths. Progress in obstetrics and neonatal intensive care competence have improved survival particularly of preterm and low birth weight neonates. These neonates, for the immunological state and the invasive therapies they are subjected to, are extremely at risk for sepsis. Knowledge of neonatal risk factors, together with cytokines evaluation as early markers of sepsis and laboratory tests such as polymerase chain reaction, have allowed us to accelerate the diagnosis of sepsis with prognostic improvements. The frequent involvement of group B streptococci and coagulase-negative staphylococci requires empiric antibiotic therapy, effective for these pathogens, in all infants with suspected infection, waiting for blood cultures and antibiotic susceptibility results. Breast milk, carrier of immunologically active agents, is still the best prophylaxis for neonatal sepsis. PMID- 11765665 TI - Knowing from whence we came: reflecting on return-to-work and interpersonal relationships. AB - Much as the medical reformers of the early 1900s believed that occupational therapists could assist patients in their efforts to rejoin society as contributing members, we believe that we can help people to lead satisfying and productive lives. Work (or productivity) and the notion of the spirit, have been entwined within occupational therapy since its inception. The connection was apparent in the badge worn by ward aides in World War I, which was described as emblematic of "the nobility of work lighting up mind, body and spirit". As in war time, when the spirit can so readily be broken, much of our work today requires us to help mend broken spirits. It is here that we use our interpersonal skills to understand our clients' view of the world, and to enter into an alliance with them; it is here that we draw upon our own sense of compassion. As we evolve in our approach to clients, and move from therapy to enabling, from being a helping profession to a service provider, let us take care to preserve the sense of compassion with which our profession came into being. That compassion will influence what we do as practitioners and how we do it. PMID- 11765666 TI - Involvement of occupational therapy departments in research: a provincial survey. AB - It is increasingly recognized that research is necessary to advance the practice of occupational therapy. The objective of this study was to determine whether occupational therapy departments in Quebec were commonly involved in research, and whether participation varied with the size of department and type of work setting. Secondly, enablers and barriers to participation in research were identified. A random sample of occupational therapy departments, stratified by size, were surveyed by mail. Participation rate was 74.8% (107/143). Participation in research was noted in half of the departments surveyed (51/107), most frequently as collaborator. Involvement in research was associated (p < .001) with a greater number of therapists in the department. Furthermore, occupational therapy departments in rehabilitation centres and in university hospitals were more likely to participate in research (79% and 90% respectively), whereas participation was lower for long-term care facilities (29%) and community health clinics (38%). When asked to rank factors that may facilitate participation in research, the highest rankings were given to: time allotted to research, research as a priority for administration, adequate financial support, and presence of an occupational therapy researcher and a research centre on site. This survey demonstrates that a number of factors can promote or prevent the realization of research activities within the clinical setting. Strategies are proposed to enhance the integration of research into clinical practice. PMID- 11765667 TI - Effects of cognitive processes and task complexity on acquisition, retention, and transfer of motor skills. AB - This experiment was designed to investigate the effect of cognitive problem solving operations (termed contextual interference) and complexity of tasks on the acquisition retention and transfer of motor skills. Ninety-six children, ages 7.5-9.5 practiced the task of throwing beanbags under either low contextual interference (blocked practice), high contextual interference (random practice) or medium contextual interference (combined practice). Half of the participants acquired a complex task and the other half a simple task. All participants performed 30 acquisition trials, 9 retention trials and 4 transfer trials. Results indicated that participants who practiced in the blocked practice group did not differ in their performance whether they acquired complex or simple tasks. On the other hand, participants from the random and combined practice groups who acquired simple tasks performed better than those who acquired complex tasks. These findings support the hypothesis that there is a limit to the interference during practice that will benefit retention and transfer, thus creating the contextual interference effect. It seems that the complex-task condition combined with random or combined practice schedule increased the difficulty of acquisition, possibly impeding the cognitive processing during acquisition, thus impairing the learning process. PMID- 11765668 TI - [Psychometric properties of a psychological well-being test for people with physical impairments]. AB - Measuring the psychological well-being of people with physical impairments could provide relevant information to occupational therapists. The aim of this study was to verify psychometric properties of a psychological well-being test called Test de personnalite PER (PER). This test was administered to two samples of people with physical impairments. Two time measurements were collected within a group of 36 individuals and one single measure within another group of 79 individuals. Comparisons between time measurements, between groups and with the normative group of the PER were performed in an attempt to verify the sensitivity, the capacity to discriminate between known groups, and the construct validity of the PER. One section of the Sickness Impact Profile measuring psychological well-being was administered to the same groups to verify the concurrent criterion validity of the PER. The results indicate that the PER has sufficient psychometric qualities. PMID- 11765669 TI - Expanding the boundaries of occupational therapy practice through student fieldwork experiences: description of a provincially-funded community development project. AB - The numbers of occupational therapists in community practice are not yet large enough to provide fieldwork placements to accommodate all students. This article describes a project designed to educate community agencies that do not employ occupational therapists, about our service while at the same time securing new fieldwork placements. We used on-site different discipline and offsite same discipline supervision to provide students to selected agencies without cost. Funding for one year from the Ontario Ministry of Health to the Ontario University Programs in Rehabilitation Science enabled us to initiate and evaluate the project. Students in the project developed their ability to work independently and to see their potential role in health promotion and prevention. Despite the lack of ongoing government funding, four years later, community sites are not only being maintained, but the number of sites has increased from 28 to 39, providing a total of 75 student placements. By educating a growing number of community agencies about the work of occupational therapists, the project has also expanded the boundaries of practice. PMID- 11765670 TI - Culture and occupation: a comparison of weaving in two traditions. AB - The ways in which cultural beliefs are reflected in the enactment of specific occupations are not well described. A comparison of weaving in the Guatemala Highlands and in Northeast Ohio was completed using interview and observation to provide detailed information about the enactment of weaving, and its meaning to women in the two cultures. Findings demonstrate that there are significant differences in content, context, pattern, affect, and meaning of the occupation. However, weavers also express similar experiences of connection with others, maintenance of tradition, and creative and spiritual expression. Findings also suggest that interventions to maintain the important meanings of the occupation must be tailored to the specific cultural beliefs of the two different groups. PMID- 11765671 TI - Effect of state workplace safety laws on occupational injury rates. AB - The purpose of this study was to evaluate the effect of four common types of mandatory state-level workplace safety regulations on injury severity rates during the period 1992 to 1997 for the manufacturing sector. The full Poisson regression model showed safety committee regulations to have a highly significant reducing effect on injury rates, chi 2 (1, n = 3286) = 10.1774, P = 0.0014. Safety program regulations were significant at the alpha = 0.10 level, chi 2 (1, n = 3286) = 3.5676, P = 0.0589. The effect of insurance carrier loss control regulations in the full model was nonsignificant. However, insurance carrier loss control regulations were highly significant (alpha = 0.01) in the final reduced model. Targeting initiatives were nonsignificant in both the full and reduced models (alpha = 0.05). The study results are important to state and federal agencies considering adopting workplace safety regulations that are similar to the four types evaluated in this study. PMID- 11765672 TI - Salivary cortisol levels and work-related stress among emergency department nurses. AB - The objective of this study was to assess and compare the self-perceived work related stress of emergency department (ED) and general ward (GW) nurses and to assess the relationship between self-perceived stress and salivary cortisol levels in these groups of nurses. Seventy-three female ED (n = 23) and GW (n = 50) nurses from a general hospital completed a self-administered questionnaire. A modified mental health professional stress scale (PSS) was used to measure self perceived work-related stress. Salivary samples were collected at the start and end of morning shiftwork. An enzyme-linked immunosorbent assay method was used to determine the salivary cortisol concentration (nmol/L). ED nurses perceived that nursing was more stressful (mean, 1.58; 95% confidence interval [CI], 1.35 to 1.81) than did GW nurses (mean, 1.30; 95% CI, 1.18 to 1.40). On the PSS subscales, scores of organizational structure and process, lack of resources, and conflict with other professionals were higher in ED nurses (all P < 0.01). The morning cortisol was significantly lower in ED (geometric mean, 9.10; 95% CI, 6.62 to 12.42 nmol/L) than in GW (geometric mean, 15.45; 95% CI, 11.86 to 20.14 nmol/L) nurses. Log morning salivary cortisol was negatively correlated with PSS (r = -0.255), scores of organizational structure and process, and conflict with other professionals (all P < 0.05). The difference between morning and afternoon cortisol concentration in ED nurses (geometric mean, 6.35; 95% CI 4.14 to 9.93 nmol/L) was lower than in GW nurses (geometric mean, 12.42; 95% CI, 9.38 to 16.28 nmol/L). The log value of the difference correlated marginally with PSS (r = 0.21, P = 0.07) and significantly with scores of organizational structure and process, lack of resources, and conflict with other professionals (all P < 0.05). There was no difference between the two groups in afternoon salivary cortisol level. ED nurses perceived more stress compared with GW nurses. Morning salivary cortisol concentration is better correlated with PSS compared with the morning afternoon salivary cortisol difference. The result raises the possibility of using a single morning salivary cortisol sample to reflect self-perceived stress. PMID- 11765673 TI - Relationship between frequency of aerobic activity and illness-related absenteeism in a large employee sample. AB - Frequency of weekly aerobic activity was compared with annual illness-related absenteeism in 79,070 adult US adult workers. Weekly exercise, days per week of aerobic activity (> or = 20 minutes), and absenteeism consisting of days per year and grouped as 1 to 3, 4 to 6, and 7+ days were recorded. After controlling for confounding variables, chi-squared values and odds ratios were calculated. A significant (chi 2 = 280.37) relationship was found between absenteeism and exercise. Differences (P < 0.05) in absenteeism were found between no exercise and all frequencies of weekly exercise. One day of exercise was associated with lower absenteeism when compared with no exercise, and 2 days of exercise was more favorable than one. No differences were found between any other combinations (2 to 3, 2 to 4+, 3 to 4+ days) of exercise frequency and absenteeism. These data suggest a significant relationship between exercise frequency and illness-related absenteeism. PMID- 11765674 TI - Symptom factor analysis, clinical findings, and functional status in a population based case control study of Gulf War unexplained illness. AB - Few epidemiological studies have been conducted that have incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls. The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of the veterans with unexplained musculoskeletal pain met the criteria for fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others. PMID- 11765675 TI - Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans. AB - Many factors have been considered as possible causes of the unexplained illness reported by veterans of the Gulf War (GW). In this study, we report an analysis of risk factors and unexplained illness in a population-based sample of GW veterans who underwent clinical evaluation. Multiple risk factors were compared in 241 veterans who met criteria for unexplained illness and 113 healthy controls. Results suggest that GW unexplained illness is most highly associated with combat conditions, heat stress, and having sought medical attention during the GW. When controlling for multiple simultaneous exposures during the GW, interactions around pyridostigmine bromide, insecticides and repellents, and stress were not significant. These results indicate that most unexplained illness in GW veterans cannot be explained by neurotoxic effects of exposures to chemicals that inhibit cholinesterase activity. PMID- 11765676 TI - Mathematical procedure to adjust for the healthy worker effect: the case of firefighting, diabetes, and heart disease. AB - This article presents a mathematical procedure to adjust for one component of the healthy worker effect (HWE), namely, the healthy hired effect, on diabetes in the case of firefighting and heart disease. Three examples from real studies are given to illustrate, step-by-step, the application of the mathematical procedure. The mathematical procedure can be applied to adjust for other components of the HWE (e.g., the low-risk hired effect on obese individuals and smokers). In such cases, additional information will be needed to use the mathematical procedure. Results of applying the mathematical procedure in the case of firefighting and heart disease revealed the rather unexpected results that adjusting for diabetes selection on hiring leads to only a 3% to 9% increase in the magnitude of ratio statistics such as the standardized mortality ratio. It might be argued that the HWE from one component such as the healthy hired effect on diabetes might be small, but together with other components, the HWE might be large. Further investigation will be needed to support this argument. PMID- 11765677 TI - Physiological responses of firefighters wearing level 3 chemical protective suits while working in controlled hot environments. AB - Firefighters in Queensland are exposed to hot, humid weather conditions that contribute to the overall workload encountered during emergency operations. Responding to certain hazardous material incidents requires firefighters to wear fully encapsulated chemical protective suits for a maximum period of 20 minutes. The nature of these suits, combined with workload and environmental conditions, poses a potential heat stress problem for firefighters. This study evaluates the heat-induced physiological responses of firefighters while wearing fully encapsulated chemical protective suits in a series of controlled thermal environments. Heart rate, body (aural) temperature, blood pressure, fluid loss, and a rating of perceived exertion were measured to evaluate the effect of increasing ambient air temperature during the performance of standard tasks. The results of the study indicated that the significant increase in heart rate, body temperature, and blood pressure was directly related to the increase in air temperature. The research indicates that the recommended suit wearing time of 20 minutes provided adequate physiological protection under the research conditions. PMID- 11765678 TI - Mental health issues in the workplace: a case for a new managerial approach. AB - Anger, stress, and depression in the workplace are growing concerns among management. Traditionally, health outcomes have functioned under the realm of workplace health professionals. This study assessed whether a traditional worksite health promotion program had an impact on mental health factors. The results suggested that worksite health promotion programs play a limited role in ameliorating work-related mental health outcomes. Rather, management must play a greater role in addressing workplace stress, anger, and depression. PMID- 11765679 TI - Associations between workload and diseases rarely occurring in sickness absence data. AB - This study provides rate ratios for sickness absence in relation to workload, which was accessed by means of a job exposure matrix. Emphasis is given to diseases that are seldom studied by sickness absence data either because the incidence is low or because medical treatment is not supplemented by rest from work. A total of 42,508 employees from the metal processing and retail trade were followed for 3 years. Sick leave related to hypertension, ischemic heart diseases, ulcer, neurotic disorders, or work accidents was most frequent in employees exposed to physical demands and low control. In contrast, an inverse relation was observed for psychological demands, for which rate ratios decreased with increasing exposure. This finding might be an expression of work commitment or pressure to attend rather than of coping behavior, because both hard and soft diagnoses were considered. PMID- 11765680 TI - Updated mortality study of workers at a petroleum refinery in Torrance, California, 1959 to 1997. AB - The updated cohort consisted of 3328 workers who were employed at the Mobil (now ExxonMobil) Torrance, California, refinery for at least 1 year between 1959 and 1997. The vital status of the cohort was determined through a variety of sources, including company employment or retirement records, the Social Security Administration's Death Master File, and the National Death Index. The updated study covered an observation period of 38 years from 1960 to 1997, with a total of 60,612 person-years of observation. A total of 705 (21.2%) cohort members were identified as having died. Mortality data were analyzed in terms of cause specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs), with expected deaths based on US national cause-, gender-, race-, year-, and age-specific mortality rates. The overall mortality of the cohort was significantly lower than expected when compared with the US general population (SMR, 81.9; 95% CI, 76.0 to 88.2). Overall cancer mortality was also lower than expected (SMR, 79.8; 95% CI, 67.9 to 93.1). For specific cancer sites, significant mortality deficits were observed for cancer of the digestive system (SMR, 70.9; 95% CI, 49.4 to 98.6) and cancer of the respiratory system (SMR, 74.1; 95% CI, 55.5 to 97.0). No significant increase was reported for any site specific cancer. For nonmalignant diseases, no significant increase was observed for any cause. In particular, significant mortality deficits were reported for ischemic heart disease (SMR, 87.7; 95% CI, 77.2 to 99.3), chronic endocardial disease and other myocardial insufficiencies (SMR, 8.3; 95% CI, 0.2 to 46.0), all other heart disease (SMR, 64.2; 95% CI, 43.0 to 92.2), and influenza and pneumonia (SMR, 59.2; 95% CI, 33.1 to 97.6). Detailed analysis by length of employment did not reveal any significant mortality excess or upward trend. Analyses of male employees by job classification (process and maintenance) were conducted. Among maintenance workers, mortality from cirrhosis of the liver (SMR, 190.1; 95% CI, 101.2 to 325.1) and suicide (SMR, 208.6; 95% CI, 111.1 to 356.7) were significantly elevated. However, these mortality excesses did not seem to be related to employment at the refinery. No other causes of death showed significant increase among maintenance workers. A similar separate analysis was conducted for process workers, and no significant excess was detected for any cause. The findings from the present study are discussed in conjunction with results from previous investigations of employees at the Torrance refinery and with results from other refinery studies. Potential limitations of the study are also discussed. PMID- 11765682 TI - Spirometric surveillance in hazardous materials firefighters: does hazardous materials duty affect lung function? AB - We analyzed spirometry results for 351 male hazardous materials firefighters from 1996 to 1999 who underwent one or more annual medical surveillance/fitness for duty examinations: 276 (79%) technicians and 75 (21%) support members. Support members had a very limited potential for hazardous materials exposure and served as referents. In cross-sectional comparisons, the technicians' average forced vital capacity and forced expiratory volume in 1 second were either statistically better or not significantly different from that of the support members at all four examinations. Longitudinally, no statistically significant differences were seen for forced vital capacity. The mean percent of predicted forced expiratory volume in 1 second decreased by 3% for technicians (P = 0.029), support controls (P = 0.433), and the total cohort (P = 0.014). Although respiratory irritants are the most common type of exposure in hazardous materials releases, the results suggest that hazardous materials technicians do not lose pulmonary function at a more accelerated rate than support team firefighters. PMID- 11765681 TI - Case-control study of intracranial tumors among employees at a petrochemical research facility. AB - This case-control study evaluated the relation between potential exposure to chemical and physical agents and the occurrence of intracranial tumors among employees at a petrochemical research facility. Cases were employees with glioma (n = 6) or benign intracranial tumors (n = 6). Controls (n = 119) were individually matched to cases on gender and birth year, and they were alive and did not have an intracranial tumor at the case's diagnosis date. Exposure information came from interviews with subjects or surrogates and from corporate records on agents used in research projects. Analyses computed matched odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for self-reported exposure to 15 agents and project-based estimates of exposure to 29 agents. For gliomas, the OR was elevated for self-reported exposure to ionizing radiation (OR, 15.7; CI, 1.4 to 179.4), n-hexane (OR, infinity; CI, 1.4 to infinity), organometallics (OR, 9.4; CI, 1.5 to 59.7), and amines other than nitrosamines (OR, 6.0; CI, 1.0 to 35.7). The OR also was elevated for project-based potential use of ionizing radiation (OR, 9.6; CI, 1.7 to 55.2) and for potential use of n hexane lasting at least 4 years (OR, 16.2; CI, 1.1 to 227.6). For benign intracranial tumors, the OR was elevated only for self-reported exposure to ionizing radiation (OR, 5.4; CI, 1.7 to 43.1) and other amines (OR, 5.2; CI, 0.9 to 29.5). Occupational exposure may have contributed to the glioma excess, but the specific causal agents remain unknown. The study indicated that benign intracranial tumors were unlikely to be work-related. PMID- 11765683 TI - Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort. AB - To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios. PMID- 11765684 TI - Comprehensive Therapy continues in its commitment to global excellence. PMID- 11765685 TI - Concise review of the management of hepatitis C. AB - Hepatitis C is the most common blood-borne infection in the US affecting at least 2.7 million Americans today. The majority of infected patients remain asymptomatic until the end-stages of the disease, making the infection difficult to identify, study, and treat. PMID- 11765686 TI - Oxidant injury in coronary heart disease (Part-I). AB - Oxidative stress damages the heart through a series of reactions beginning with lipid peroxidation, the main process behind atherosclerosis. Antioxidant supplementation has some beneficial effects by binding with metal ions or catalysts to prevent oxidative lipid peroxidation and chain production. PMID- 11765687 TI - Noninvasive drug delivery. AB - Advances in biopharmaceutical technology have spawned new drug delivery devices and mechanisms. Noninvasive methods, including iontophoresis and transmucosal drug delivery, have improved treatment of certain patient population. Their use is discussed in the following paper. PMID- 11765688 TI - Evaluation of hearing impairment. AB - Hearing impairment is among the most common medical condition presenting to health care professionals. Ear anatomy, physiology, and pathology resulting in hearing loss are discussed. A systematic approach to evaluation, diagnosis, and treatment is presented. PMID- 11765689 TI - Management of pneumothorax and barotrauma: current concepts. AB - Pneumothorax can be spontaneous, traumatic or iatrogenic. Pneumothorax ex vacuo, sports-related pneumothorax and barotrauma unrelated to mechanical ventilation are interesting and newer entities. Management consists of getting rid of the air and prevention of recurrence of pneumothorax. PMID- 11765690 TI - Aging, cumulative disability, and the compression of morbidity. AB - The Compression of Morbidity paradigm emphasizes reduction in cumulative disability by postponing chronic infirmity. This article describes the model, reviews data suggesting morbidity compression over time, establishes associations between health risks and subsequent disability, and describes risk reduction interventions. PMID- 11765691 TI - Brain injuries in sports: guidelines for managing concussions. AB - Guidelines for assessment of head injuries and prevention of serious deficits depend on clinical assessment. These cost effective interventions are supplemented by imaging studies when findings warrant. PMID- 11765692 TI - Effect of scleral expansion band on ocular hypertension: Canadian phase 1 study. AB - A prospective, nonrandomized, controlled, phase 1 clinical trial was conducted to evaluate use of the scleral expansion band for lowering elevated intraocular pressure (IOP) in patients with ocular hypertension or primary open-angle glaucoma. The procedure lowered IOP by increasing outflow. PMID- 11765693 TI - Working together to reduce medical errors. PMID- 11765694 TI - Confusion in clinical engineering. PMID- 11765695 TI - Making a difference ... biomeds reach out to provide aid and expertise to countries in need. PMID- 11765696 TI - Preparing for the challenges of 2002. PMID- 11765697 TI - Effectively utilizing device maintenance data to optimize a medical device maintenance program. AB - Methods developed by the clinical engineering community and the principles outlined by ISO regulations for the application of risk management to medical devices were integrated to provide a basis for the unique optimization system implemented into the University Health Network medical device maintenance program. Device maintenance history data stored in the database is used to conduct a risk analysis and to compute predefined benchmarks to highlight groups of equipment for which the current maintenance regime is not optimal. Using a software data research tool we are able to investigate device history data and support alterations in maintenance intervals, user training, maintenance procedures, and/or device purchasing. These alterations are justified, documented, and monitored for risk in a continuous management cycle. The predicted benefits are an overall improvement in the reliability of the devices maintained, coupled with a drop in repetitive device checks that result in no measurable benefits. PMID- 11765698 TI - The effect of repeated ethylene oxide sterilization on the mechanical strength of synthetic absorbable sutures. AB - The purpose of this study was to determine the effect of repeated ethylene oxide sterilization using a standard clinical protocol on sutures, a type of medical device labeled for single use and reported to be reprocessed for use after being opened but not used. Four types of commonly used synthetic absorbable sutures were subjected to 1 and 2 ethylene oxide resterilization cycles. Knot tensile strength was determined for new sutures and for sutures that had been subjected to 1 and 2 ethylene oxide resterilization cycles. As has been found with other types of single-use devices, no general conclusions can be made for absorbable sutures. The strengths of different types of sutures increased, decreased, or stayed the same after repeated sterilization. In addition, the inner packages of some sutures were not intact after reprocessing, possibly exposing the sutures to increased humidity, which can produce degradation leading to loss of strength both immediately and after additional shelf aging and degraded performance after clinical use. PMID- 11765699 TI - Noninvasive blood pressure performance: a reproducible method for quantifying motion artifact tolerance in oscillometry. AB - Motion artifact tends to degrade oscillometric noninvasive blood pressure measurement (NIBP) accuracy and other aspects of performance (measurement time, patient comfort, false-positive readings). Medical personnel generally have not fully appreciated the extent of these degradations, in part because NIBP provides no waveform display to allow visualization of artifact disruption (unlike the electrocardiography (ECG) and pulse oximetry (SpO2) patient channels). More importantly, the magnitude and frequency of NIBP errors has also gone unappreciated because the auditory noise produced by transport vibration prevents accurate quantification of NIBP accuracy by the traditional auscultatory method. To overcome these problems, a commercially available NIBP simulator was modified to permit the superimposition of repeatable motion artifact waveforms from a function generator onto known patient blood pressure profiles available in the NIBP simulator. The superimposed artifact waveforms had been collected under transport conditions. This methodology enabled comparisons between artifact-free NIBP readings, on the one hand, and artifact-contaminated readings on the other. Monitors under test were subjected to multiple combinations of patient and artifact profiles. Measurement errors were expressed as a percent deviation of the artifact-contaminated readings from the expected (artifact-free) readings. Statistical analyses of the data compared the performance of the different monitor types with nonparametric tests of inference (Kruskal-Wallis H test, Mann Whitney U test, and chi-squared test). These analyses demonstrated statistically significant differences in performance including accuracy, yield (incidence of values within various error categories), retries, measurement time, and false positive readings under artifact-only conditions. The method further demonstrated that the monitor using ECG synchronization to filter motion artifact achieved statistically and clinically significant improvements in accuracy without compromising clinical expectations for measurement time. This approach provided a reproducible and quantifiable method by which to assess and differentiate the artifact tolerance of different NIBP technologies. PMID- 11765700 TI - How can you reduce turnover? Three concepts pave the way. PMID- 11765701 TI - A perfusionist's perspective. Communicating beyond boundaries. PMID- 11765702 TI - The automatic endoscope reprocessor. PMID- 11765703 TI - Looking for long-term solutions to the health care labor shortage. PMID- 11765704 TI - DOI, CrossRef, LINK, and the future of scientific publishing. PMID- 11765705 TI - Orthodontic treatment--yes or no? A difficult decision in some cases. A contribution to the discussion. AB - Reasons for orthodontic treatment are discussed on the basis of 1. evidence-based knowledge from the literature, 2. viewpoints based on clinical experience, 3. case presentations. Viewpoints regarding prophylactic aspects of orthodontic treatment in relation to oral health are critically evaluated. The clinically based experience that dentofacial esthetics is the main reason for most patients requesting orthodontic treatment is also well documented in the literature. Against this background, psychosocial aspects as an indication for orthodontic treatment deserve greater recognition. PMID- 11765706 TI - Craniofacial growth pattern in cover-bite malocclusions and its therapeutic influencing. AB - SUBJECT: The present investigation deals with the questions of whether there is a typical craniofacial morphology in cases with cover-bite malocclusions, whether this type correlates with variation in population, and whether this growth pattern can be influenced by treatment with removable appliances. PATIENTS AND METHOD: The issue was approached by studying lateral cephalograms of 75 subjects (35 males, 40 females) divided into three groups of 25 subjects each: German cover-bite patients, Syrian cover-bite patients, and subjects with neutroclusion. Overall 125 lateral cephalograms were studied with 13 reference lines and 18 reference angles being taken into account. The data obtained were subjected to statistical analyses using the t-test to detect significant group differences. RESULTS: The results revealed that there are characteristic features in cover bite patients in comparison to subjects with neutroclusion and that these features are partly subject to interpopulation differences as well as to interindividual variations. With regard to orthodontic treatment the cover-bite craniofacial morphology is marginally influenceable. PMID- 11765707 TI - Clinical application and effects of the Forsus spring. A study of a new Herbst hybrid. AB - BACKGROUND: The best known of the fixed functional appliances are the Herbst appliance and the Jasper Jumper. The Forsus spring is a new development which has been tested in a clinical study to establish when it can be used and to compare it with its predecessors. PATIENTS AND METHOD: The Forsus spring was used over a period of 4 months to treat 13 patients with an average age of 14.2 years with Class II malocclusion. RESULTS: Evaluation of the lateral cephalograms showed that dental effects accounted for 66% of the sagittal correction. The sagittal occlusal relations were improved by approximately 3/4 of a cusp width to the mesial on both the right and left side as a result of distal movement of the upper molars and mesial movement of the lower molars. Retrusion of the upper and protrusion of the lower incisors reduced the overjet by 4.6 mm. Intrusion and protrusion of the lower incisors reduced the overbite by 1.2 mm. The occlusal plane was rotated by 4.2 degrees in clockwise direction as a result of intruding the lower incisors and the upper molars. The maxillary and mandibular arches were expanded at the front and rear during treatment.--Evaluation of a questionnaire filled in by the patients after 2 months of treatment showed that approximately half of them had experienced difficulties in brushing their teeth. The main problem, however, was the restriction experienced in the ability to yawn. Overall, two thirds of the adolescents found the Forsus spring better than the appliance previously used to correct their Class II malocclusion, such as headgear, activator or Class II elastics. CONCLUSION: The Forsus spring has stood the test in clinical application. It is a good supplement to the Class II appliance systems already available. PMID- 11765708 TI - Two- or three-dimensional cast analysis in patients with cleft lip and palate? AB - AIM: The aim of the present study was to evaluate different two- and three dimensional cast analyses for the assessment of maxillary dimensions in patients with complete unilateral cleft lip and palate, using a set of representative cast series. PATIENTS AND METHOD: Consecutive casts were taken from ten patients at 1 week, and at 3, 6, and 12 months, respectively. First, cast surfaces were digitized two-dimensionally using a scanner. Subsequently, landmarks were identified on screen and the previously defined maxillary dimensions were determined automatically by computer. Additionally, three-dimensional measurements were carried out using a specialized coordinate measurement table. The differences between the respective measurements were analyzed for statistical significance. RESULTS: The present study shows that the precision of the cast analysis is influenced above all by the quality of the casts and less by the precision of the measuring system employed. Moreover, misinterpretation of the results can be attributed to using an inappropriate reference system or to considering mean values only. When assessing linear and angular measurements located in approximately the same plane, no significant amount of additional information could be obtained by including the third dimension. CONCLUSION: Thus, two-dimensional measurement procedures are appropriate in principle for quick, reliable cast analysis in patients with cleft lip and palate. PMID- 11765709 TI - A cephalometric evaluation of the Biobloc technique using matched normative data. AB - PATIENTS AND METHOD: The outcome of Biobloc treatment was evaluated on 35 patients, 13 male, 22 female, with Class II, Division 1 malocclusions. Cephalometric radiographs were taken before and after treatment. A control group was generated from published normative data in such a way that each treated case was matched individually for age, sex and treatment time. The cephalometric change during treatment was compared to the natural growth change in the matched control group using a Mann-Whitney U-test. The treatment effect was calculated by subtracting the natural growth change from the treatment change. This was then compared to twice the method error to see if the treatment change was clinically significant. RESULTS: There was both a statistically and a clinically significant reduction in overjet (p < 0.001), overbite (p < 0.001) and angle ANB (p < 0.001) with an increase in angle SNB (p < 0.001). None of the other cephalometric parameters measured showed a significant change except for upper incisor proclination (p < 0.05) and ArGoMe angle (p < 0.05) but these were not clinically significant. PMID- 11765710 TI - Early cellular reactions in mechanically stimulated gingival connective tissue. AB - AIM: The aim of this study was to describe early cellular reactions occurring in mechanically stimulated gingival connective tissue. MATERIAL AND METHOD: Elastic bands were inserted between the maxillary first and second molars of male rats aged 8 weeks, which were pulse-labeled with 3H-thymidine and subsequently killed in groups together with labeled control animals after periods of 1-168 hours. Autoradiographs were prepared from plastic mesiodistal sections and parameters of cell proliferation determined in gingival connective tissue sampling areas coronal to the interdental bone crest and in the central zone of the body of the papilla between the second and third molars. The incidence of macrophages was assessed in identical tissue compartments of adjacent sections by counting nonspecific esterase-positive cells, and the vascular reaction was evaluated by measuring vascular lumen area and endothelial cell proliferation. RESULTS: Fibroblast and endothelial cell proliferation was significantly increased in mechanically stimulated tissue (p < 0.05) compared with controls, the incidence of macrophages was very low both in control and in stimulated specimens, and an immediate but transient vasodilatation occurred as part of the gingival tissue response to stimulation (p < 0.05). CONCLUSION: The results question the role of macrophages at the early stages of gingival remodeling incident to mechanical stimulation. PMID- 11765711 TI - Bioterrorism: defending the public's health in a time of national crisis. PMID- 11765713 TI - U.S. hospitals, physicians playing "catch-up" on bioterrorism. PMID- 11765712 TI - Crisis communications. PMID- 11765715 TI - [New memorial dedicated to victims of the Warsaw uprising]. PMID- 11765714 TI - Coping with terrorism: lessons of Oklahoma City. PMID- 11765717 TI - 28th Annual meeting of the Japanese Society of Toxicology. June 10-12, 2001. Tokyo, Japan. Abstracts. PMID- 11765716 TI - Is it possible to orally vaccinate juvenile red foxes against rabies in spring campaigns? AB - The rabies antibody status of juvenile foxes (Vulpes vulpes) was evaluated in large-scale, long-term oral vaccination campaigns. Between 9% (n = 659) and 21% (n = 42) of the juvenile foxes examined in 1993-94 and 1997, respectively, showed rabies virus neutralizing antibody (nAb)-titers > or = 0.5 IU/ml following bait distribution in spring. The presence of nAb may be due to either the passive transfer of maternal antibodies, or active immunization derived from spring vaccination campaigns. The latter alternative is supported by the finding of nAb throughout late spring and the summer months, and the finding of the tetracycline (TC) biomarker, used in the vaccine-baits, in 27% (n = 43) and 37% (n = 155) of juveniles in 1993-94 and 1997, respectively. It was not possible to distinguish nAb originating from passive immunity from that arising from active immunization. However, biological data on the whelping period of red foxes, on dynamics of maternal antibodies and the timing of oral vaccination, gave evidence that a superposition of these processes is likely. Evidence from these studies suggests that oral vaccination coinciding with the spring perinatal period may produce immunity in both parents and only in a certain percentage of the offspring simultaneously. This phenomenon should be useful in further enhancing the efficacy of oral vaccination in red foxes. PMID- 11765718 TI - Politics and research ethics. PMID- 11765719 TI - [Physiopathology of deglutition disorders in the aged and the treatment]. PMID- 11765720 TI - [The 43rd Congress of the Japanese Society of Clinical Hematology. Kobe, Japan. November 13-15, 2001. Program and Abstracts]. PMID- 11765722 TI - [Menopause: social and practical representations]. AB - OBJECTIVE: To characterize the meanings attributed to menopause, as a first approximation to the representational world of this event. MATERIAL AND METHODS: A qualitative study was conducted between September and October 1998, in twenty women aged 45-65 years, residents of Cuernavaca and Emiliano Zapata, municipalities of Morelos state, Mexico. Twenty in-depth interviews were conducted using a guide, to collect data on sociodemographic variables, diagnosis, feelings and emotions, changes in life style, and physiological changes. RESULTS: Findings show that menopause is represented as the end of fertility and the beginning of old age. Characterization of menopause is related to womanhood, body, and sexuality representations. CONCLUSIONS: This paper analyzes women's practices related to life experiences such as medical visits. Implications of these findings are discussed using the social construction of meanings framework. PMID- 11765723 TI - [Policies and programs of food and nutrition in Mexico]. AB - Mexico has a long-standing history of programs and policies oriented to improve the nutrition of vulnerable groups. However, malnutrition represents one of the main public health challenges in Mexico. This article provides a historic perspective of the main strategies, programs and policies that have been carried out in Mexico, as well as a detailed analysis of their design, implementation, and selected results. Finally, some critical issues related to food policies implemented in Mexico are identified. PMID- 11765724 TI - Imatinib mesylate. PMID- 11765725 TI - The role of magnetic resonance cholangiography in the management of children and young adults after liver transplantation. AB - We reviewed the results of 50 magnetic resonance (MR) cholangiograms to evaluate their usefulness in directing clinical management in young patients after liver transplantation (LTx). Thirty-two patients underwent 50 MR cholangiograms on a 1.5-T unit. Studies were performed from 1 week to 16 yr after LTx. Indications included biochemical abnormalities with (n = 19) or without (n = 16) biopsy evidence for chronic rejection, sepsis (n = 14), and intractable ascites (n = 1). Original interpretations were compared to laboratory and ultrasound findings, and clinical outcome. Of 19 studies performed on 14 patients with biopsy evidence of chronic rejection, 16 were abnormal on MR (but only one was abnormal on ultrasound), resulting in corrective surgery (n = 1), re-Tx (n = 1), and endoscopic dilatation (n = 1). Of 16 studies on 16 patients with biochemical abnormalities without evidence of chronic rejection on biopsy, 14 were abnormal on MR (but only five of 13 on ultrasound), leading to corrective surgery (n = 3) and re-listing for Tx (n = 3). Thirteen of 14 studies on six patients with sepsis were abnormal on MR (five of nine were abnormal on ultrasound), identifying surgically correctable strictures (n = 2), and leading to re-Tx (n = 1) and percutaneous biliary drainage procedures (n = 2). The one patient with ascites had a normal study. We advocate usage of MR cholangiography for the detection of biliary complications after LTx, particularly in those patients who present with biochemical abnormalities that are not easily explained by acute cellular rejection or viral infection and in those with biliary sepsis. PMID- 11765726 TI - Pediatric renal transplantation: a single Belgian center experience over 20 years. AB - Between 1980 and 2000, 100 renal transplantations were performed in 91 children at the pediatric unit of the University Hospital Leuven. The proportion of living related donors (LRD) was 20%. Patient survival rates were 94% at 3 yr, 91% at 5 yr, and 87% at 10 yr. The commonest causes of death were bacterial infections and cardiovascular complications, which underscores the need for aggressive preventative procedures in this area after transplantation. The overall actuarial graft survival was 82% at 3 yr (n = 73), 74% at 5 yr (n = 53), and 56% at 10 yr (n = 29). In the LRD group, the graft survival was 10% better than the overall actuarial graft survival rate. The overall incidence of acute rejection was 55% but has shown a decrease to 34% in more recent years (1993-99). The major causes of graft failure were chronic rejection and recurrence of the initial disease, and these remain a major concern. Improvement of these results could be achieved by tight immunosuppression management, early aggressive treatment of infection and rejection, and careful educational and psychological support. PMID- 11765727 TI - [National congress on "fatigue" in the oncology patient with the sponsorship of the Italian Association of Medical Oncology. Rome, June 5-6, 2001]. PMID- 11765728 TI - [Irinotecan and fluorouracil in combination in colorectal carcinoma: a little clarity]. PMID- 11765729 TI - [Doxorubicin and paclitaxel versus 5-fluorouracil, doxorubicin and cyclophosphamide as first-line treatment in women with metastatic breast carcinoma: final results of a phase III multicenter randomized trial]. PMID- 11765730 TI - Storage and retrieval of addition facts: the role of number comparison. AB - It is proposed that arithmetical facts are organized in memory in terms of a principle that is unique to numbers--the cardinal magnitudes of the addends. This implies that sums such as 4 + 2 and 2 + 4 are represented, and searched for, in terms of the maximum and minimum addends. This in turn implies that a critical stage in solving an addition problem is deciding which addend is the larger. The COMP model of addition fact retrieval incorporates a comparison stage, as well as a retrieval stage and a pronunciation stage. Three tasks, using the same subjects, were designed to assess the contribution of these three stages to retrieving the answers to single-digit addition problems. Task 3 was the addition task, which examined whether reaction times (RTs) were explained by the model; Task 1 was a number naming task to assess the contribution of the pronunciation stage; Task 2 was a magnitude comparison task to assess the contribution, if any, of the comparison stage. A regression equation that included just expressions of these three stages was found to account for 71% of the variance. It is argued that the COMP model fits not only the adult RT data better than do alternatives, but also the evidence from development of additional skills. PMID- 11765731 TI - Inspection times, the change task, and the rapid-response selection task. AB - Three experiments are reported, which are based upon the Wason four-card selection task inspection time paradigm, in which subjects solve computer presented trials while using a mouse to indicate the card currently under consideration. Evans (1996) had shown that selected cards were inspected for longer than non-selected cards, and this was taken as support for the existence of pre-conscious heuristic processes that direct attention towards relevant aspects of a problem. However, Roberts (1998b) suggested that this inspection time effect is artefactual, due to task format induced biases. Experiment 1 utilized a "change" task: Cards were presented either as selected or not selected, and subjects changed these where necessary. This demonstrated an association between card selection and inspection time independently of one between the act of response and inspection time. Experiment 2 utilized a standard selection task, but subjects either responded within 2 s of each card presentation, or made selections with no time pressure. The curtailment of thinking time increased matching behaviour--more cards matching the terms in the rules were selected--and was replicated in Experiment 3 using a within-subjects design. Overall, the data support Evans' heuristic-analytic framework albeit with some caveats. PMID- 11765732 TI - The implicit benefit of learning without errors. AB - Two studies examined whether the number of errors made in learning a motor skill, golf putting, differentially influences the adoption of a selective (explicit) or unselective (implicit) learning mode. Errorful learners were expected to adopt an explicit, hypothesis-testing strategy to correct errors during learning, thereby accruing a pool of verbalizable rules and exhibiting performance breakdown under dual-task conditions, characteristic of a selective mode of learning. Reducing errors during learning was predicted to minimize the involvement of explicit hypothesis testing leading to the adoption of an unselective mode of learning, distinguished by few verbalizable rules and robust performance under secondary task loading. Both studies supported these predictions. The golf putting performance of errorless learners in both studies was unaffected by the imposition of a secondary task load, whereas the performance of errorful learners deteriorated. Reducing errors during learning limited the number of error correcting hypotheses tested by the learner, thereby reducing the contribution of explicit processing to skill acquisition. It was concluded that the reduction of errors during learning encourages the use of implicit, unselective learning processes, which confer insusceptibility to performance breakdown under distraction. PMID- 11765733 TI - What colour is the car? Implicit memory for colour information in children. AB - Three experiments were conducted to examine age-related differences in colour memory. In Experiment 1, preschool age and elementary school age children were given a conceptual test of implicit colour memory (a colour-choice task). They were presented with the names or achromatic versions of previously studied coloured line drawings and asked to select an appropriate colour. Significant priming could be demonstrated: The children chose the previously seen colours more often than was expected by chance. Equivalent priming was found for both versions (pictorial and verbal) suggesting that colour priming may be conceptually mediated. Moreover, colour priming proved to be age invariant. Experiment 2 replicated and extended this finding by using a wider age group (preschool, elementary school, and young adults) and by giving a perceptual implicit task (picture identification) in addition to a verbal colour-choice task. Colour did not affect priming in the perceptual task. Whereas priming showed no developmental change, age-related improvements were observed on an explicit colour memory task that differed only in the test instructions from the implicit colour-choice task (Experiments 2 and 3). Taken together, the results suggest that implicit colour memory may be mediated by conceptual processes that are age invariant. PMID- 11765734 TI - The relationship between the structural mere exposure effect and the implicit learning process. AB - Three experiments are reported that investigate the relationship between the structural mere exposure effect (SMEE) and implicit learning in an artificial grammar task. Subjects were presented with stimuli generated from a finite-state grammar and were asked to memorize them. In a subsequent test phase subjects were required first to rate how much they liked novel items, and second whether or not they thought items conformed to the rules of the grammar. A small but consistent effect of grammaticality was found on subjects' liking ratings (a "structural mere exposure effect") in all three experiments, but only when encoding and testing conditions were consistent. A change in the surface representation of stimuli between encoding and test (Experiment 1), memorizing fragments of items and being tested on whole items (Experiment 2), and a mismatch of processing operations between encoding and test (Experiment 3) all removed the SMEE. In contrast, the effect of grammaticality on rule judgements remained intact in the face of all three manipulations. It is suggested that rule judgements reflect attempts to explicitly recall information about training items, whereas the SMEE can be explained in terms of an attribution of processing fluency. PMID- 11765735 TI - Selective attention modulates implicit learning. AB - The effect of selective attention on implicit learning was tested in four experiments using the "contextual cueing" paradigm (Chun & Jiang, 1998, 1999). Observers performed visual search through items presented in an attended colour (e.g., red) and an ignored colour (e.g., green). When the spatial configuration of items in the attended colour was invariant and was consistently paired with a target location, visual search was facilitated, showing contextual cueing (Experiments 1, 3, and 4). In contrast, repeating and pairing the configuration of the ignored items with the target location resulted in no contextual cueing (Experiments 2 and 4). We conclude that implicit learning is robust only when relevant, predictive information is selectively attended. PMID- 11765736 TI - Auditory negative priming in speeded reactions and temporal order judgements. AB - Two experiments are reported that demonstrate negative priming for auditory stimuli. Reaction times and temporal order judgements were used as the dependent measures in Experiments 1 and 2, respectively. In Experiment 1, participants classified tones presented to one ear as wind or string instruments while ignoring tones presented to the other ear. The task was identical for both the prime and the subsequent probe presentations. Probe reactions were slower for previously ignored tones than for tones that had not occurred during the prime presentation. Probe reactions to previously attended tones were faster than reactions to nonrepeated tones. In Experiment 2, the probe reactions were replaced by temporal order judgements. The probability of accepting a tone as antecedent was lower for previously ignored primes than for new tones. No difference was observed between previously attended and new tones. The results are compatible with the conclusion that distractor inhibition is a necessary component of the processes that bring about observable negative priming phenomena. PMID- 11765737 TI - The automaticity of complex motor skill learning as a function of attentional focus. AB - The present experiment was designed to test the predictions of the constrained action hypothesis. This hypothesis proposes that when performers utilize an internal focus of attention (focus on their movements) they may actually constrain or interfere with automatic control processes that would normally regulate the movement, whereas an external focus of attention (focus on the movement effect) allows the motor system to more naturally self-organize. To test this hypothesis, a dynamic balance task (stabilometer) was used with participants instructed to adopt either an internal or external focus of attention. Consistent with earlier experiments, the external focus group produced generally smaller balance errors than did the internal focus group and responded at a higher frequency indicating higher confluence between voluntary and reflexive mechanisms. In addition, probe reaction times (RTs) were taken as a measure of the attention demands required under the two attentional focus conditions. Consistent with the hypothesis, the external focus participants demonstrated lower probe RTs than did the internal focus participants, indicating a higher degree of automaticity and less conscious interference in the control processes associated with the balance task. PMID- 11765738 TI - Semantic priming of person recognition: categorial priming may be a weaker form of the associative priming effect. AB - An interactive activation and competition account (Burton, Bruce, & Johnston, 1990) of the semantic priming effect in person recognition studies relies on the fact that primes and targets (people) have semantic information in common. However, recent investigations into the type of relationship needed to mediate the semantic priming effect have suggested that the prime and target must be close associates (e.g., Barry, Johnston, & Scanlan, 1998; Young, Flude, Hellawell, & Ellis, 1994). A review of these and similar papers suggests the possibility of a small but non-reliable effect based purely on categorial relationships. Experiment 1 provided evidence that when participants were asked to make a name familiarity decision it was possible to boost this small categorial effect when multiple (four) primes were presented prior to the target name. Results from Experiment 2 indicated that the categorial effect was not due to the particular presentation times of the primes. This boosted categorial effect was shown to cross domains (names to faces) in Experiment 3 and persist in Experiment 4 when the task involved naming the target face. The similarity of the pattern of results produced by the associative priming effect and this boosted categorial effect suggests that the two may be due to the same underlying mechanism in semantic memory. PMID- 11765739 TI - Spatial modulation of repetition blindness and repetition deafness. AB - When two identical visual items are presented in rapid succession, people often fail to report the second instance when trying to recall both (e.g., Kanwisher, 1987). We investigated whether this temporal processing deficit is modulated by the spatial separation between the repeated stimuli within both audition and vision. In Experiment 1, lists of one to three digits were rapidly presented from loudspeaker cones arranged in a semicircle around the participant. Recall accuracy was lower when repeated digits were presented from different positions rather than from the same position, as compared to unrepeated control pairs, demonstrating that auditory repetition deafness (RD) is modulated by the spatial displacement between repeated items. A similar spatial modulation of visual repetition blindness (RB) was reported when pairs of masked letters were presented visually from either the same or different positions arranged on a semicircle around fixation (Experiment 2). These results cannot easily be accounted for by the token individuation hypothesis of RB (Kanwisher, 1987; Park & Kanwisher, 1994) and instead support a recognition failure account (Hochhaus & Johnston, 1996; Luo & Caramazza, 1995, 1996). PMID- 11765740 TI - Separating effects of orthographic similarity and contour summation in the identification of masked letter strings. AB - We separated effects of contour summation and orthographic similarity under masking conditions, by comparing identification with simultaneous and sequentially presented letter strings, which either did or did not overlap spatially. With overlapping simultaneous stimuli, performance was better for strings with similar contours than for strings with the same letters (the orthographic similarity condition). This suggests that contour summation effects were strongest in the condition where stimuli had similar contours. With sequential presentations, performance in the similar contour and the orthographically similar conditions was equated when the stimuli were overlapping. However, effects of contour summation decreased when prime and target letters were spatially displaced, whereas performance in the orthographically similar condition was maintained. We conclude that effects of orthographic similarity can be distinguished from effects of contour summation, under masking conditions. PMID- 11765741 TI - Inhibition of return at multiple locations in visual search: when you see it and when you don't. AB - Using a novel sequential task, Danziger, Kingstone, and Snyder (1998) provided conclusive evidence that inhibition of return (IOR) can co-occur at multiple non contiguous locations. They argued that their findings depended crucially on the allocation of attention to cued locations. Specifically, they hypothesized that because subjects could not predict whether an onset event was a target or a non target, all onset events had to be attended. As a result, non-targets were tagged with inhibition. The present study tested this hypothesis by manipulating whether target onset was predictable or not. In support of Danziger et al., three experiments revealed that multiple IOR was only observed when attention had to be directed to the cued locations. Interestingly, when attention did not need to be allocated to the cued locations, and multiple IOR was abolished, an IOR effect was still observed at the most recently cued location. Two possible accounts for this single IOR effect were presented for future investigation. One account attributes the effect to motor-based inhibition as hypothesized by Klein and Taylor (1994). The alternative account attributes the effect to weak attentional capture by a peripheral cue. Together the data support the view that multiple IOR is an attentional phenomenon and, as hypothesized by Tipper, Weaver, and Watson (1996), its presence or absence is largely under the control of the observer. PMID- 11765742 TI - A comparison of upper vs. lower and right vs. left visual fields using lexical decision. AB - A series of experiments using the lexical decision task was conducted in order to investigate the functional differences between the upper and lower visual fields (UVF, LoVF) in word recognition. Word-nonword discrimination was swifter and more accurate for word stimuli presented in the UVF. Changing the eccentricity did not affect the UVF advantage over the LoVF. UVF superiority over LoVF was found to be equivalent for both right and left visual hemifield (RVF, LVF). In general, presenting related word primes enhanced all visual field differences in a similar manner (UVF over LoVF and RVF over LVF). However, primes consisting of semantically constraining sentences enhanced the RVF advantage over the LVF, but did not affect the UVF and LoVF differentially. The argument is made that UVF superiority cannot be due to perceptual or attentional differences alone, but must also reflect top-down information flow. PMID- 11765743 TI - Review essay. "How strange are the tricks of memory". PMID- 11765744 TI - Enhanced discrimination in autism. AB - Children with autism are superior to typically developing children at visual search tasks (O'Riordan, Plaisted, Driver, & Baron-Cohen, in press; Plaisted, O'Riordan, & Baron-Cohen, 1998b). This study investigates the reasons for this phenomenon. The performance of children with autism and of typically developing children was compared on a series of visual search tasks to investigate two related problems. The first issue was whether the critical determinant of search rate in children is the discriminability of the display items, as it is in normal adults. The second question investigated was whether the superior performance of individuals with autism on visual search tasks is due to an enhanced ability to discriminate between display items. The results demonstrated that discriminability is the rate-determining factor for children with and without autism, replicating earlier findings with normal adults, and that children with autism have an enhanced ability to discriminate between display items. Thus, it seems that an enhanced ability to discriminate between display items underlies superior visual search in autism. PMID- 11765745 TI - There are stable individual differences in performance variability, both from moment to moment and from day to day. AB - Individual differences in decision speed have been regarded as direct reflections of a "primitive" functional neurophysiological characteristic, which affects performance on all cognitive tasks and so may be regarded as the "biological basis of intelligence", or of age-related changes in mental abilities. More detailed analyses show that variability within an experimental session (WSV) is a stable individual difference characteristic and that mean choice reaction times (CRTs) are gross summary statistics that reflect variability, rather than maximum speed of performance. A total of 98 people aged from 60 to 80 years completed 36 weekly sessions on six different letter categorization tasks. After effects of practice and of circadian variability had been eliminated, individuals with lower scores on the Cattell Culture Fair intelligence test had slower CRTs and greater WSV on all tasks. A simulation study showed that the greater WSVs of low Cattell scorers led directly to the significantly greater variability of their mean CRTs from session to session. However because CRTs on tasks co-varied from session to session it was apparent that, besides being affected by WSV, individuals' between session variabilities (BSVs) also vary because of state changes that affect their performance from day to day. It seems that both variability in performance from trial to trial during a session and variability in average performance from day to day are correlated, stable, individual difference characteristics that vary inversely with intelligence test performance. Methodological consequences of these results for interpretations of age-related cognitive changes, for variability between as well as within individuals, for individual differences in decision speed, and for circadian variability in performance are discussed. PMID- 11765746 TI - Photo quiz. Purple discoloration in a urinary catheter bag. PMID- 11765747 TI - After Chanukah. PMID- 11765748 TI - Informed choice in cancer screening. PMID- 11765749 TI - Canine feces as a reservoir of extraintestinal pathogenic Escherichia coli. PMID- 11765750 TI - Editorial. PMID- 11765751 TI - Ethics committees in Italy--a time for change? AB - The Comitato Nazionale per la Bioetica (CNB) in Italy has recently produced an unprecedented discussion document on the state of ethics committees in Italy, with an invitation to interested parties to comment on proposed changes to their fundamental structure. After this consultation, and taking note of relevant official publications and the most recent national and international literature on the subject, the CNB proposes to produce a final, definitive document that will consider options for the future development of such committees. PMID- 11765752 TI - How the GMC hears a case of alleged misconduct. PMID- 11765753 TI - [The report from the XIX National Congress of Polish Historians of Medicine and Pharmacy]. PMID- 11765754 TI - [The history of internal medicine in Poznan from the year 1919]. AB - After the 1st World War (1914-1918) the greatest influences in the development of internal medicine were the foundation of Poznan University and its first Dean Prof. H. Swiecicki - a physician. Due to cooperation with Prof. A. Wrzosek the School of Medicine was created. In addition to those mentioned above were the first creators of internal medicine Professors: W. Jezierski, J. Lubieniecki and I. Hoffmann. During World War II Poznan medicine suffered badly. After the War there was a renewal of Poznan and in internal medicine appeared excellent leaders: prof. J. Roguski, prof. S. Kwasniewski and prof. F. Labendzinski. Thanks to them 1st 2nd and 3rd Departments of Internal Medicine transformed in narrow specialized departments integrated in the Institute of Internal Disease and led by prof. K. Jasinski and his vice head prof. J. Hasik and prof. M. Gembicki. In the 1985 there appeared from Internal Institute the Institute of Cardiology with the head prof. A. Cieslinski. There was also overworked the status of out-clinic internal medicine (prof. I. Zimmerman-Gorska, dr W. P. Kasprzak). PMID- 11765755 TI - [Ludwik Hirszfeld (1884-1954) the Wroclaw Years, 1945-1954]. AB - Beginning with an initial overview of his earlier activities as a scholar, this article is a study of the years which Ludwik Hirszfeld spent in Wroclaw and is based on published sources as well as the reminiscences of both his colleagues and of this author. Hirszfeld himself, in his described his life autobiography "History of One Life" until just after the Second World War. The years he spent in Wroclaw organizing the Medical Department, of which he was the first director from 1945-1946 were unusually active ones. Hirszfeld was also at that time founder of the Department of Medical Microbiology and later of the Institute for Immunology and Experimental Therapy of the Polish Academy of Sciences in Wroclaw. He was simultaneously involved in highly successful scientific research particularly in the area of immunopathology during pregnancy. He was a popular lecturer on this subject with a special gift for reaching his audience as well as an active participant in scientific discussions in a variety of foral forums. He had a great personal influence on the first generation of staff and students of the Medical Department in Wroclaw in the years immediately following the end to the Second World War. PMID- 11765756 TI - [Archival materials collected by Prof. Wiktor Dega in the Department of the History of Medical Sciences, Karol Marcinkowski University of Medical Sciences - general characteristics]. AB - Interesting archival materials collected by Prof. Wiktor Dega are held in the Department of the History of Medical Sciences belonging to Karol Marcinkowski University. There are mainly personal documents including: a military booklet, passport and different identity cards. They are also the diary from 1913. Noteworthy are the notebooks from his student period and diaries full of reflections from his scientific journeys abroad and chrestomathy from the professional literature. Moreover, the archival material about Prof. Degas' pre war activity and a organiser of cost-free gymnastic courses for children with posture defects should be mentioned in Poznan. After the Second World War Prof. Dega worked on the Committee of Rehabilitation and Adaptation of Human Beings and organised the Polish Branch of the International College of Surgeons, and materials from that time are also available. Also important are documents associated with Prof. Dega's the Order of Smile from the St. Maria Magdelena secondary school in Poznan. His letters are extremely valuable and the interesting press articles, photos and diplomas are also noteworthy. PMID- 11765757 TI - [School hygiene in Wielkopolska from 1920 to 1939]. AB - Between The First and The Second World Wars school hygiene was as important as other medical disciplines. In 1922 Stanislow Kopczynski created an act which concerned sanitary demands for schools being built. The importance of the health and growth of children had been noticed. In 1931 there were 8 school doctors working in Poznan. At that time Poznan was one of four centres engaged in research concerning school hygiene (the other being Warsaw, Krakow and Wilno). A School Sanitary Science Department (E. Piasecki), Anthropological Department (A. Wrzosek, M. Cwirko-Godycki) and Orthopedic Clinic (W. Dega), all at Poznan University were involved. The scientific attainments of these departments was regularly presented at school doctors' meetings. A periodical magazine "Physical Education" (E. Piasecki) was published from 1920 to 1933. In 1939 "School hygiene" (M. Cwirko-Godycki) is was being published quarterly. PMID- 11765758 TI - [The origin of concept and role of the National Congresses of Polish Historians of Medicine]. PMID- 11765759 TI - [Cooperation between pharmacists of Gdansk and Wielkopolska region in the XX century]. AB - The University of Poznan, with its Pharmaceutical Department was established after the First World War. Many of the pharmacists educated in Poznan were employed in the Pomorze Gdanskie region. This article describes the activities of these pharmacists in the years 1920-1939 and during the Second World War. The article also discusses the assistance of the University of Poznan in the organization of the Pharmaceutical Faculty of the Medical University of Gdansk and of pharmacy in the Pomorze Gdanskie region. Those pharmacists who came back to Poznan after years spent at the Baltic seaside and those who studied in Gdansk and were then employed in Poznan are also mentioned in the article. PMID- 11765760 TI - [The origin of the Wilno Obstetric and Gynaecological Clinic and its roots, which reach as far back as the 18th century]. AB - Studies carried out in libraries and archives in Wilno, Cracow, Warsaw and Gdansk raven how the clinic of obstetrics and gynaecology was created in Wilno, describe the first years activity, and the persons who had the greatest influence on its creation and position. This clinic, which was organized by Tadeusz Burdzinski and developed by Wladyslaw Jakowicki in cooperation with Waclaw Zaleski, functioned in the years 1922-1939. In its scarcely 17 years of existence this clinic had a marked presence among the Polish clinics of obstetrics and gynaecology in the Second Republic (II RP). In the author's opinion this fact can be traced back to the roots of obstetrics and gynaecology in the university in Wilno, which reach as far as the 18th century and the person of Mikolaj Regnier. For the first half of the 19th century the gynaecologists and obstetrics of Wilno includes Andrzej Matusewicz and Mikolaj Mianowski carried out their scientific activities outside the University for nearly 80 years. It seems that this activity, which lead to numerous publications, is the platform upon which rests continuous scientific tradition of obstetrics and gynaecology in Wilno and lets us see to present clinic in the University of Stefan Batory - in 21st surely century - as her heiress of that tradition. PMID- 11765761 TI - Anorexia nervosa and respecting a refusal of life-prolonging therapy: a limited justification. AB - People who suffer from eating disorders often have to be treated against their will, perhaps by being detained, perhaps by being forced to eat. In this paper it is argued that whilst forcing compliance is generally acceptable, there may be circumstances under which a sufferer's refusal of consent to treatment should be respected. This argument will hinge upon whether someone in the grip of an eating disorder can actually make competent decisions about their quality of life. If so, then the decision to refuse therapy may be on a par with other decisions to refuse life-prolonging therapy made by sufferers of debilitating chronic, or acute onset terminal illness. In such cases, palliation might justifiably replace aggressive therapy. The argument will also draw heavily on the distinction between competent refusal of therapy and passive euthanasia, and the distinction between incompetence and irrational decisions. Both distinctions will then be applied to decisions to refuse food. The extent to which sufferers from anorexia nervosa can be categorised as either incompetent or irrational will be examined. It against this background that it will be argued that at least some of those who suffer from eating disorders should have their refusals respected, even if they may die as a result. PMID- 11765762 TI - The beginning of personhood: a Thomistic biological analysis. AB - 'When did I, a human person, begin to exist?' In developing an answer to this question, I utilize a Thomistic framework, which holds that the human person is a composite of a biological organism and an intellective soul. Eric Olson and Norman Ford both argue that beginning of an individual human biological organism occurs at the moment when implantation of the zygote in the uterus occurs and the 'primitive streak' begins to form. Prior to this point, there does not exist an individual human organism, but a cluster of biological cells which has the potential to split and develop as one or more separate human organisms (identical twinning). Ensoulment (the instantiation of a human intellective soul in biological matter) does not occur until the point of implantation. This conception of the beginning of human personhood has moral implications concerning the status of pre-implantation biological cell clusters. A new understanding of the beginning of human personhood entails a new understanding of the morality of certain medical procedures which have a direct affect on these cell clusters which contain human DNA. Such procedures discussed in this article are embryonic stem cell research, in vitro fertilization, procured abortion, and the use of abortifacient contraceptives. PMID- 11765763 TI - International research ethics. AB - This article provides a critical overview of the most important issues pertaining to the ongoing debate on international research ethics. It critically describes three problems of continuing concern: 1) the question of whether the distinction between therapeutic and non-therapeutic research should be upheld; 2) the questions of whether currently demanded best proven diagnostic and therapeutic methods of treatment for all research subjects is feasible both in developed and in developing countries, and whether it should be upheld; 3) the questions of who owns international research ethics guidelines and regulatory frameworks and, how decisions about changes to such international guidelines can possibly be achieved, given that it seems to be the case that genuine disagreement about issues of content is possible and likely. PMID- 11765764 TI - Owning genetic information and gene enhancement techniques: why privacy and property rights may undermine social control of the human genome. AB - In this article I argue that the proper subjects of intangible property claims include medical records, genetic profiles, and gene enhancement techniques. Coupled with a right to privacy these intangible property rights allow individuals a zone of control that will, in most cases, justifiably exclude governmental or societal invasions into private domains. I argue that the threshold for overriding privacy rights and intangible property rights is higher, in relation to genetic enhancement techniques and sensitive personal information, than is commonly suggested. Once the bar is raised, so-to-speak, the burden of overriding it is formidable. Thus many policy decisions that have been recently proposed or enacted--citywide audio and video surveillance, law enforcement DNA sweeps, genetic profiling, national bans on genetic testing and enhancement of humans, to name a few--will have to be backed by very strong arguments. PMID- 11765765 TI - Editorial. PMID- 11765766 TI - The ethics of xenotransplantation. AB - Xenotransplantation--moving organs or cells from one species to another--is currently being actively researched as a possible contribution to the problem of a global shortage of human organs for transplants. Should xenotransplantation be encouraged, permitted, frowned upon or forbidden? I attempt to outline the main areas of debate that would need to be addressed before this question could confidently be answered. At present, though, we are some way from answering it. This is partly because of the lack of agreement among bioethicists about almost anything and partly because xenotransplantation raises a particularly wide range of ethical issues. PMID- 11765767 TI - Identity and disability. AB - There are various methods of avoiding giving birth to a disabled child. Many have the result that people who would otherwise be born are not born. Gene therapy is among these methods. Yet it seems to have the advantage of neither ending, nor preventing from starting, certain possible lives. Rather it allows the continuation, with improvements, of a life already under way. But is this true? I consider what two influential identity theorists will have to say about this problem. A Kripkean account strongly suggests that therapy does not affect the identity of the person who will be born. But a Parfittian account, in contrast, appears to hold that insofar as psychology is affected, so too is identity. Of the two, I favour Parfit's account. Gene therapy, performed on a human embryo, can affect the identity of the person to be born. But then I go on to argue that the disagreement that is here resolved was never as profound as it might have appeared. Although there are scientific questions about the physical and psychological results of gene therapy, and although there are questions too about the links between different parts of our discourse, there is not, I claim, any deep issue about the nature, or the metaphysics, of identity. PMID- 11765768 TI - Now you see it, now you don't; consent and the legal protection of autonomy. AB - In this paper I describe the piecemeal development of the law regarding capacity to consent to treatment. I note how the requirement has changed from Justice Cardozo's low-level requirement of a 'sound mind' to the relatively high-level Re C test. I discuss the limitations of the Re C test. Particularly, that the requirements from believing information and ability to weigh information in the balance--which should be applied to the patient's ability to decide and not the actual treatment decision--are open to subjective abuse and the risk of abductive inferences made from the patient's actual decision. I suggest that, because of a generally poor standard of reasoning ability, only a minimal level of rationality should be required. Furthermore, I demonstrate the fallacy of the judicially approved risk related standard and discuss the Catch-22 situation that arises when it is implemented. PMID- 11765770 TI - [Vasoconstrictor responsiveness of rat basilar artery enhanced by simulated weightlessness]. AB - OBJECTIVE: To investigate the effects of simulated weightlessness on contractile responsiveness of the basilar artery. METHODS: Rats were subjected to tail suspension for 4-wk to simulate the effect of weightlessness, responses of perfused isolated basilar arterial rings to various vasoactive compounds were examined. RESULTS: Maximal isometric contractile responses to KCl [ (10~100) mmol/L], arginine vasopressin [AVP, (10(-15)~10(-7) mol/L], or 5 hydroxytryptamine [5-HT, (10(-12) ~ 10(-4) mol/ L] were significantly enhanced in arterial rings isolated from 4-wk tail-suspended as compared with that from simultaneous control rats. CONCLUSION: These results indicate that medium-term simulated weightlessness may result in an enhanced contractile responsiveness in rat basilar artery, and strongly support the hypothesis of cerebrovascular syncope-initiating mechanism. PMID- 11765769 TI - Effects of tea polyphenols on cerebral lipid peroxidation, liver and renal functions in rats after repeated +Gz stress. AB - OBJECTIVE: To observe the effects of repeated +10 Gz stress on cerebral lipid peroxidation, liver and renal function in rats and the prophylactic effects of antioxidant tea polyphenols (TP). METHOD: Twenty-four male Wistar rats were randomly divided into three groups (n = 8, each): group A (control), group B (+10 Gz), and group C (TP). Group B and C were exposed to repeated +10 Gz stress (each for 30s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP (200 mg/kg) was given orally in group C about 1 h prior to the +Gz experiment, while distilled water was given in group A and B. Lipid peroxidation in the brain, liver and renal functions and serum lipids were determined. RESULTS: As compared with the control, lipid peroxidation in rat cerebral homogenate, mitochondria and cytoplasm was significantly increased (P < 0. 05), and serum creatinine concentration was markedly elevated after repeated +10 Gz stress (P < 0. 01). But, TP had significant inhibitory effect on +10 Gz stress induced peroxidative injury in rat brain and reduced the serum creatinine level. There were no differences of serum triglyceride and total cholesterol concentrations and glutamic-pyruvic transaminase activity among the three groups. CONCLUSION: These results indicated that repeated high +Gz stress could bring about peroxidative injury in brain and harmful effect on renal function, and natural antioxidant TP had significant protective effects. PMID- 11765772 TI - [Comparison between motion sickness induced by reversed vision and that by parallel swing]. AB - OBJECTIVE: To make clear the characteristics of motion sickness induced by reversed vision and to see whether it can be used in motion sickness experiments. METHODS: 10 healthy young men experienced walking tests wearing up-down or left right reversing prisms, and parallel swing test on different days with intervals of 5-7d. Ataxia and motion sickness symptoms induced by walking wearing reversing prisms and those by parallel swing were observed. The reversed vision tolerance index (RVTI) and linear acceleration tolerance index (LATI) were calculated by an empirical formula. RESULTS: Both types of reversing prisms can induce obvious ataxia and motion sickness symptoms. The ataxia is correlative (P<0.05) with the susceptibility to motion sickness. In comparison with symptoms of swing motion sickness, the symptoms of reversed vision motion sickness are not too serious and appear slowly. There are correlativities (P< 0.01) between the susceptibility to motion sickness induced by up-down and left-right reversing prisms. The susceptibilities to motion sickness induced by reversing prisms are not correlative completely with that by swing. CONCLUSION: Reversed vision test is simple and easy and can be used for simulating space motion sickness or training of adaptation to sensory conflict on the ground. PMID- 11765771 TI - [Effect of -6 degrees head-down-bed-rest on human cellular immune function]. AB - OBJECTIVE: To observe the effect of -6 degrees head-down bed-rest on proliferation of lymphocyte and production of certain cytokines. METHODS: 6 healthy young men served as the subjects. Peripheral blood lymphocyte was assayed 1d prior to and on the 3rd day and 6th day of bed rest. RESULTS: The production of IFN-alpha on the 3rd day was markedly decreased (P < 0.05), but killing activity of NK was significantly enhanced (P < 0.05), production of IFN-gamma and expression of IL-2 receptor were all slightly reduced. Both production of IFN alpha and killing activity of NK resumed to the control level on the 6th day, production of IFN-r and CD25 were significantly lowered (P < 0.05) on the 6th day, a lymphocyte proliferation and production of IL-2 were gradually decreased with time, but production of IL-6 was gradually increased. CONCLUSION: -6 degrees head-down bed-rested has certain effect on cellular immune function in man. PMID- 11765773 TI - [Effects of mild and moderate hypoxia on event-related potentials and the comparison of different stimulus paradigms]. AB - OBJECTIVE: To investigate the effects of mild and moderate hypoxia on event related potentials (ERP), and to compare the sensitivity of different stimulus paradigms to hypoxia. METHODS: Twelve subjects performed visual Oddball and memory set size (MSET) 1 and MSET 3 of Sternberg tasks on the ground and at the simulated altitudes of 2500 m and 4300 m by breathing low oxygen mixtures. P3 latency and amplitude of ERP, reaction time (RT) and response error rate (ER) were recorded. RESULTS: During hypoxia at the altitude of 4300 m, P3 latency significantly delayed, and ER was high when the difficulty of task increased (Sternberg paradigm with MSET 3). In contrast, at the altitude of 2500 m no changes were observed. Sternberg paradigm with MSET 1, in comparison with others, could elicit clearer ERP waves, and P3 latency was slower during hypoxia. CONCLUSION: Hypoxia at the altitude of 4300 m has strong influence on ERP. P3 latency can be used as a sensitive index in evaluating the decrement of brain cognitive capacity during hypoxia. ERP elicited by Sternberg paradigm with MSET 1 was more sensitive to hypoxia. PMID- 11765774 TI - [Effect of noise on human mental performance]. AB - OBJECTIVE: To investigate the effect of moderate noise on human thinking performance. METHODS: During 2 h of exposure to 85, 90 dB(A), successive calculation, successive subtraction and determining figures according symbol were performed in 24 healthy young male subjects. RESULTS: After l h exposure to noise of 85 dB(A), there were no significant changes in the accurate rate, correct number and total number of successive calculation, but the correct number and total number of successive subtraction decreased significantly as compared with control (P< 0.05). At 30 and 120 min exposure to noise of 90 dB(A), the mean reaction time prolonged, performance of reaction time decrease significantly (P<0.01) in the test of determining figures according symbol as compared with control; its total performance had a tendency of decrease, but was not significant. When the subjects were divided into two group according to their E score of EPQ, significantly different performance of accurate rate and different total performance were demonstrated in the test of determining figures according to symbol at 2 h of exposure under 90 dB(A) noise. The performance of extrovert was higher than that of introvert. CONCLUSION: Moderate noise could affect performance of complex tasks with a higher workload and it had certain relationship with the personality of the subjects. PMID- 11765775 TI - [Biological effects of space flight on purple nonsulfur photosynthetic bacteria]. AB - OBJECTIVE: To study biological effects of space flight on purple nonsulfur photosynthetic bacteria. METHODS: Two purple nonsulfur photosynthetic bacteria, Rhodopseudomonas palustris H3 and Rhodobacter sphaeroides ZGY, were carried on satellite for 15 days and some of their biological effects were studied after recovery. RESULTS: In space condition, survival rate of bacteria was promoted. The purification of organic wastewater, removal of nitrite, degradation of phenol and decolorization of acid red B were enhanced, and the resistance of both strains to medicine was stable. CONCLUSION: The major morphological and physiological characteristics of loaded strains H3-S and ZGY-S were not changed after space flight. PMID- 11765776 TI - [Two high performance fighter pilots with low +Gz tolerance rectified by centrifuge training]. AB - OBJECTIVE: To demonstrate the effects of training on rectifying two high performance fight aircraft pilots with low +Gz tolerance. METHODS: Anti-G straining maneuver (AGSM) and pressure breathing for +Gz (PBG) maneuver were trained during centrifuge +Gz stress. RESULTS: After training, the +Gz tolerances with AGSM, and with PBG and anti-G suit were enhanced by 3.0 ~ 3.25 G and 2.75 ~ 3.0 G, respectively. The combined +Gz tolerance was higher than the relaxed +Gz tolerance by 4.25 ~ 4.5 G. Both two pilots had passed the 8 G 10 s SACM +Gz profile and reached the standard of training. PMID- 11765777 TI - [Counteracting effect of hypoxia and Qigong on cardiac rhythm during orthostatic test post simulated weightlessness]. AB - OBJECTIVE: To try to find a new method for countermeasuring the effect of simulated weightlessness. METHODS: The study was carried out in fifteen male healthy subjects, 19-22 years, -6 degrees head-down bed rest (-6 degrees HDBR) for 21 d was used as a weightlessness simulation model. The subjects were divided into three groups: control group (-6 degrees HDBR), hypoxia group (-6 degrees HDBR + inhalation of hypoxic gas mixture two times a day, 20 min each time) and Qigong group (-6 degrees HDBR + Qigong, three times per day, 45 min each time). Orthostatic test (+75 degrees 20 min) was conducted on each subject pre- and post HDBR. RESULTS: Cardiac rhythm during the orthostatic test was normal pre-HDBR but sinus cardiac arrhythmias were observed in two subjects of the control group and nodal cardiac arrhythmias were observed in two subjects in Qigong group after HDBR. No cardiac arrhythmia was found in hypoxia group. CONCLUSION: Hypoxia is more effective in countermeasuring orthostatic intolerance after weightlessness than Qigong. PMID- 11765778 TI - [Recording and analysis of EGG and its application in space medicine]. AB - To demonstrate the use of EGG in space medicine, especially in motion sickness, biological basis, recording, analysis of EGG used in space medicine, especially in motion sickness studies, were introduced. Several parameters of EGG were related to nausea in motion sickness. It is suggested that EGG can be used in studying nausea symptoms of motion sickness. PMID- 11765779 TI - [The development and applications of digital signal processing (DSP)-chip]. AB - Due to the limitation of operation speed, real time performance of digital signal processing (DSP) system is far from that of analog signal processing system in decades ago. Since early 80's, DSP chips have been greatly improved in the following aspects: operation speed, computation precision, fabrication technics, cost, chip volume, operational power supply voltage, weight and power consumption. Furthermore, development tools and methods have been developed greatly. Modern DSP chips can be operated very fast, which make the implementation of many DSP based signal processing system possible. Now DSP chips have been widely applied successfully in communication, automatic control, aerospace and medicine. DSP based technology has very promising future in manned space flight area. PMID- 11765780 TI - Fourier transform infrared and Raman spectral analysis of trans-1,4-polyisoprene. AB - Polyisoprene is the most widely used polymer in industry and commerce. Fourier transform infrared (FTIR) and Raman spectra of trans-1,4-polyisoprene have been recorded in the range of 4000-400 and 4000-100 cm(-1), respectively. In the present investigation, detailed assignments of the observed fundamental bands of trans-1,4-polyisoprene has been analysed in terms of peak positions and relative intensities. With the hope of providing more and effective information on the fundamental vibrations, a normal co-ordinate analysis has been performed on trans 1,4polyisoprene, by assuming Cs symmetry. The simple general valance force field (SGVFF) method has been employed in normal co-ordinate analysis and to calculate the potential energy distribution (PED) for each fundamental vibration. The PED contribution corresponding to each of the observed frequencies shows the reliability and accuracy of the spectral analysis. The validity of the SGVFF method as a practical tool for complete analysis of vibrational spectra, even for a polymer of this complexity, is confirmed in the present work. PMID- 11765781 TI - Vibrational spectra study of the isomerizational reaction of nitryl hydride. AB - The vibrational spectral study of the isomerization reaction of nitryl hydride is presented in this paper. The isomerizational reaction includes old bond rupture, new bond formation and electronic transfer in the intramolecule. For the isomerizational reaction, the vibrational modes, the vibrational frequencies and the force constants of the reactant, the transition states and product are analyzed. The relationship and the change among them can confirm the rupture of bond, the formation of bond and the process of electron transfer. PMID- 11765782 TI - Interaction of morin with CTMAB: aggregation and location in micellar. AB - The aggregation and location of morin in CTMAB micellar solution was studied by light scattering spectra, electronic absorption spectra and pulsed FT NMR techniques. The difference in the light scattering property of morin with and without CTMAB proved that a large particle of the morin-CTMAB associate formed. Morin has a self-assembly tendency, but the assembly number is not high. With the increase of morin concentration, morin changed from a monomer to dimer. The hyperchromic and bathochromic effect of morin, with the increase in pH value or PMID- 11765783 TI - Chemiluminescence flow sensor for folic acid with immobilized reagents. AB - A novel chemiluminescence (CL) sensor for folic acid combined flow-injection (FI) technology was presented in this paper. The analytical reagents involved in the CL reaction, including luminol and hexacyanoferrate(III), were both immobilized on an anion-exchange column in FI system. The CL signal produced by the reaction between luminol and hexacyanoferrate(III), which were eluted from the column through sodium phosphate injection, was decreased in the presence of folic acid. The CL emission was correlated with the folic acid concentration in the range from 0.01 to 15 microg ml(-1), and the detection limit was 3.5 ng ml(-1) folic acid (3sigma). At a flow rate of 2.0 ml min(-1), including sampling and washing, could be performed in 2 min with a relative standard deviation of < 2.5%. The flow sensor could be reused more than 300 times and has been applied to the analysis of folic acid in pharmaceutical preparations. and the recovery was from 97.4% to 100.4%. PMID- 11765784 TI - The behavior of hydroxyl units of synthetic goethite and its dehydroxylated product hematite. AB - The behavior of the hydroxyl units of synthetic goethite and its dehydroxylated product hematite was characterized using a combination of Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) during the thermal transformation over a temperature range of 180-270 degrees C. Hematite was detected at temperatures above 200 degrees C by XRD while goethite was not observed above 230 degrees C. Five intense OH vibrations at 3212-3194, 1687-1674, 1643-1640, 888-884 and 800-798 cm(-1), and a H2O vibration at 3450-3445 cm(-1) were observed for goethite. The intensity of hydroxyl stretching and bending vibrations decreased with the extent of dehydroxylation of goethite. Infrared absorption bands clearly show the phase transformation between goethite and hematite: in particular. the migration of excess hydroxyl units from goethite to hematite. Two bands at 536-533 and 454-452 cm(-1) are the low wavenumber vibrations of Fe-O in the hematite structure. Band component analysis data of FTIR spectra support the fact that the hydroxyl units mainly affect the a plane in goethite and the equivalent c plane in hematite. PMID- 11765785 TI - The effect of modifiers on the fluorescence and life-time of Gd3+ ions doped in borate glasses. AB - The effect of glass modifiers on the fluorescence and life time of the 6P(7/2) energy state of the Gd3+ ion has been investigated. A shift in the energy of maximum of the fluorescence has been observed. The results are explained on the basis of the relative cation and anion field strengths due to modifiers. A variation in the life-time of the 6P7.2 energy state of the Gd3 ion has also been noted. PMID- 11765786 TI - Synthesis, DTA, IR and Raman spectra of penthylenediammonium hexachlorostannate NH3(CH2)5NH3SnCl6. AB - The Raman and IR spectra of NH3(CH2)5NH3SnCl6 have been measured at ambient temperature. It is shown that the cations in the compound assume a symmetry lower than C2v. Combination bands observed in the 2100-1800 cm(-1) region in the IR spectrum of NH3(CH2)5NH3SnCl6 indicate that the compound contains the C-NH3 grouping, the bands are discussed and their assignment are suggested. No evidence of existence of hydrogen bonding is found from the infrared spectrum in the region of 2800-3200 cm(-1); anions and cations are found not connected by hydrogen bonding and are therfore isolated. The Raman spectrum of anions can be interpreted in terms of disordered groups, not clearly showing the predicted splitting of bands. PMID- 11765787 TI - Reaction of metallotetraphenylporphyrins on hydroxyl-modified silver colloid and Ag2O colloid by surface-enhanced Raman scattering. AB - This paper reports a novel reaction of metallotetraphenylporphyrins on hydroxyl modified silver colloid and Ag2O colloid. Surface-enhanced Raman spectra of Ag(II) and Cu(II) complexes of tetraphenylporphyrin (TPP) adsorbed on the hydroxyl-modified Ag colloid and Ag2O colloid have been studied. The time dependent SERS spectra of MTPP (M = Ag, Cu) on hydroxyl-modified Ag colloid were recorded and dramatic change on SERS spectra was observed. The final spectra were found to be strikingly different from the corresponding normal Raman spectra (NRS), with the appearance of new Raman bands at 1614. 1417, 947, 674 and 292 cm( 1). The UV-visible absorption spectrum of MTPP on hydroxyl-modified Ag colloid exhibits a broad shoulder near 460 nm. Similar spectral phenomena were also observed for AgTPP and CuTPP adsorbed on Ag2O colloid. The observed spectral alterations were ascribed to new species formation due to the irreducible oxidation of MTPP on the colloids. PMID- 11765788 TI - Spectroscopic study of the interactions of alkali fluorides with D-xylose. AB - The interactions of alkali fluorides with D-xylose have been studied by X-ray diffraction (XRD), infrared spectroscopy (IR), nuclear magnetic resonance (NMR, 1H and 13C) and atomic absorption spectrophotometry. KF and CsF form complexes with D-xylose in a 1:1 molar ratio. These complexes can be obtained by solid state milling the reactants in an agate mortar or from methanolic solutions of the sugar and the salt. LiF and NaF do not form complex with D-xylose. IR and XRD prove the identical nature of the complexes obtained by milling and from solution. IR spectra indicate strong perturbation of the OH stretching vibrations with considerable shifts to lower frequencies, which must be caused by strong hydrogen bond formation to the fluorine anion. The perturbations of C-O bond are weak, indicating that cation binding to the oxygen atoms is not the main interaction responsible for the complex formation. 1H NMR spectra of the D-xylose KF complex dissolved in deuterium oxide is equal to that of pure D-xylose, indicating the destruction of the complex in solution. The complex is stable in DMSO, and 13C spectra of the complex in DMSO-d6 and in solid state (CPMAS) spectra are in accordance with the observed interactions in the IR spectra. As far as we know, this is the first report of a sugar-halide salt complex in which the anion instead of the cation provides the binding forces. PMID- 11765789 TI - Spectral characteristics of 2-(4'-N,N-dimethylaminophenyl)pyrido[3,4-d]imidazole in AOT/n-heptane/water reverse micelles. AB - Spectral characteristics of 2-(4'-N,N-dimethylaminophenyl)pyrido[3,4-d]imidazole (DMAPPI) have been studied in AOT/n-heptane/water reverse micelles at w0 > or = 0. Absorption, fluorescence excitation and fluorescence spectra have revealed that the monocation (MC) of DMAPPI, protonated at the imidazole nitrogen (MC2) (Scheme 2) is present in the S0 state at w0 = 0, along with the MC, protonated at pyridine nitrogen (MC3) and only normal emission is observed from both MC2 and MC3. With increase in w0 (water amount), the equilibrium is shifted towards the MC, protonated at -NMe2 group (MC1) and MC3 in the S0 state. Biprotonic phototautomerism is observed in MC1 to generate MC2 in the S1 state. The twisted intramolecular charge transfer (TICT) emission replaces the normal emission in MC3. All the MCs are present near the anionic polar head group of AOT in the bound water region. PMID- 11765790 TI - Infrared spectroscopic study of mixed copper-cobalt and copper-nickel formate dihydrates (cation distribution in mixed crystals). AB - The infrared (IR) spectra of Co(HCOO)2 x 2H2O, Ni(HCOO)2 x 2H2O and Cu2Co(Ni)1-x (HCOO)2 x 2H2O mixed crystals (0 < x < or = 0.5) have been recorded and the internal modes of the formate groups and the water molecules are discussed. The analysis of the spectra of the mixed crystals reveals that when copper ions replace cobalt and nickel ions in Co(HCOO) x 2H2O and Ni(HCOO)2 x 2H2O, the Cu2+ ions are localized at the two available positions. However, the occupancy degree of the Me(1) and Me(2) sites by the different cations needs X-ray diffraction (XRD) studies of the single crystals. The new crystal phase Co0.17Cu0.83(HCOO)2 x 2H2O obtained from the Co(HCOO)2 x 2H2O-Cu(HCOO)2 x 2H2O-H2O system at 50 degrees C crystallizes in the monoclinic system with lattice parameters: a = 12.329(4); b = 7.241(2); c = 8.707(5) A and beta = 103.13(3) degrees (SG probably P2/c). The number of the bands corresponding to the uncoupled OD vibrations and the water librations shows that probably more than two water molecules are expected to exist in the structure. Furthermore, it is assumed that the water molecules bonded to the copper ions form stronger hydrogen bonds (stronger Cu-OH2 interaction) than those bonded to the cobalt ions. PMID- 11765791 TI - Semiempirical infrared spectra simulations for some aromatic amines of interest for azo dye chemistry. AB - A set of semiempirical methods (PM3, AM1, MNDO, MNDO3, INDO, CNDO and ZINDO/1) has been tested to find the best tool for the identification of aromatic amines by infrared spectroscopy. Analysed were 1,4-, 1,3-, 1,2-phenylenediamines and aniline, amines commonly used in the dye industry. Of all the semiempirical methods tested, AM1 showed the closest correspondence to experimental values. It provided the best linearity between the calculated and experimental frequencies (correlation coefficient, cc = 0.9993). In the range of -NH2 stretching vibrations, the best correspondence between the theoretical and experimental frequencies was achieved for the PM3 method (cc = 0.8369). PMID- 11765792 TI - Ab-initio molecular geometry and normal coordinate analysis of pyrrolidine molecule. AB - The molecular geometry of pyrrolidine was quantum mechanically calculated using the split valence 6-31G** basis set. Electron correlation energy has been computed employing MP2 method. The molecule showed an envelope form puckered structure with inter-plane angle of 36.4 degrees and has a total energy of 132976.80 kcal mol(-1) of which a -464.86 kcal mol(-1) electron correlation energy. The twist form of the molecule showed a twist angle of 10.2 degrees from planarity and has a total energy of -132976.05 kcal mol(-1) involving -464.097 kcal mol(-1) electron correlation energy. The normal coordinates of the molecule were theoretically analyzed on the basis of the Cs point symmetry of the envelope form. Using initial set of force constants obtained from the ab-initio calculations the fundamental vibrational frequencies were computed. The IR and laser Raman spectra of Pyrrolidine molecules were measured. All the observed vibrational bands including combination bands and overtones were assigned to normal modes with the aid of the potential energy distribution values obtained from normal coordinate calculations. The molecular force field was obtained by refining the initial set of force constants using the least square fit method. The molecular force field was determined by refining the initial set of force constants using the least square fit method instead of using the less accurate scaling factor methods. The determined molecular force field has produced simulated frequencies best match to the observed values. The low frequency molecular out-of-plane deformation modes were observed in both infrared and Raman spectra at 298 and 163 cm(-1). The barrier of ring twisting estimated from the observed ring out-of-plane vibrational mode at 163 cm(-1) was found 3.1 kcal mol( 1). PMID- 11765793 TI - Infrared studies of tautomerism in 2-hydroxypyridine 2-thiopyridine and 2 aminopyridine. AB - The infrared spectra of 2-hydroxypyridine (2-OHP), 2-thiopyridine (2-SHP), and 2 aminopyridine (2-NH2P) have been recorded in the solid, liquid and vapor phases in the region 4000-200 cm(-1). To support the work, deuterated forms of these compounds in the functional groups XH and NH with (X=O, S, NH) were recorded for the solid and liquid phases. The results show existence of each compound as an equilibrium mixture of two tautomers in monomeric and cyclic dimeric forms in the solid, liquid and vapor phases. The monomers are predominant in the vapor phase. Enthalpy differences between the monomeric tautomers and activation energies for their inter-conversion were determined in each phase. PMID- 11765794 TI - Evolution of absorption, fluorescence, laser and chemical properties in the series of compounds perylene, benzo(ghi)perylene and coronene. AB - Absorption. fluorescence and laser properties of perylene, benzo(ghi)perylene and coronene are studied experimentally (under the same conditions) and quantum chemically at room (293 K) and at low (77 and 4 K) temperatures and direct comparison is made between the results for each molecule. All the main absorption and fluorescence parameters such as oscillator strength, fe, quantum yield, gamma, decay time, tauf, fluorescence rate constant, kf (Einstein coefficient, A) and intersystem crossing rate constant, kST, are measured or calculated. The systems of singlet and triplet levels for these compounds are simulated and analyzed. Triplet states mixing with the lowest singlet S1 state are determined. The low values of kST found are explained. The possible vibronic coupling in the molecule coronene is discussed. The nature of the three fluorescence bands of coronene observed is interpreted. The change in the arrangement of the singlet and triplet levels of the studied compounds is interpreted quantum-chemically. It is found that at room temperature (293 K), only perylene shows laser action, while all three compounds show good laser oscillation at low temperature (< 100 K). The differences in the laser properties of these compounds are explained by the inversion of the Sp(1La) and Sinfinity(1Lb) levels which occurs in the transition from perylene to benzo(ghi)perylene. Chemical properties of the compounds studied are outlined. Linear and quasi-linear fluorescence spectra of perylene and benzo(ghi)perylene, obtained at 77 and 4 K. can be used in the identification of these compounds. PMID- 11765796 TI - Step-scan photoacoustic fourier transform and X-rays photoelectron spectroscopy of oil sands fine tailings: new structural insights. AB - The chemical and physical properties of clay suspensions from oil sands have profound effect not only on the bitumen extraction process but also on the tailing treatment and reclamation. Step-scan Photoacoustic Fourier Transform Infrared (S2PAS-FTIR) has been used to characterize the properties of clay suspensions. The photoacoustic spectral features of the fine solids (FS) fraction were found to vary drastically with the modulation frequency. This is attributed to the increase in the relative amount of bitumen-like matter in the bulk. A similar behavior was observed on the bi-wetted solid (BWS) fraction, in spite of the fact that the variation as a function of the modulation frequency is less significant. No such change is observed on hydrophobic solid (HPS) sample. These observations allow us to refine our pictorial image of the bitumen fraction materials structure. PMID- 11765795 TI - Absorption spectra of 7, 7, 8, 8-tetracyanoquinodimethane in micellar solutions. AB - The absorption spectra of 7, 7, 8, 8-tetracyanoquinodimethane (TCNQ) with nonionic surfactant. Triton X-100, anionic surfactant, SLS and cationic surfactant, CTAB in aqueous and nonaqueous media have been studied. The spectral studies show that TCNQ forms 1:1 charge-transfer (CT) complex with Triton X-100 in both media. The aqueous solution of TCNQ shows an absorption maxima at 610 nm, which is unperturbed in the presence of SLS but is shifted to 650 nm in the presence of CTAB, indicating the interaction of TCNQ with the cationic surfactant and not with the anionic surfactant. In addition to this, the stability of TCNQ Triton X-100 complex has been determined and the probable site of CT interaction has been pointed out. PMID- 11765797 TI - Interaction of cyanine dyes with nucleic acids. XVIII. Formation of the carbocyanine dye J-aggregates in nucleic acid grooves. AB - Spectral properties of carbocyanine dye 3-methyl-2-[3-methyl-2-(3-methyl-2,3 dihydro-1,3-benzothiazole-2-iliden)-1- butenyl]-1,3-benzothiazole-3-il iodide (Cyan betaiPr) in water solution, as well as in the presence of different types of double stranded DNA have been studied. While in water solution of 'free' dye Cyan betaiPr stays mainly in monomeric form, in the presence of DNA the dye molecules form J-aggregates. The molecular structure of these J-aggregates causes the Davydov splitting of their absorption band, corresponding to the first electronic transition. A study of site-specificity showed that in the presence of poly (dA/dT) the majority of Cyan betaiPr molecules form J-aggregates, while in the presence of poly (dGC/dGC) dye molecules stay mainly in monomeric form and in presence of chicken erythrocytes DNA both J-aggregate and monomeric forms of dye are present. We suppose that Cyan betaiPr molecules aggregate in DNA groove, which serves as a template for J-aggregate forming. An increase of ionic strength of solution leads to the release of dye molecules from DNA grooves and prevents J aggregates formation. PMID- 11765798 TI - Comment on 'new infrared spectra and tautomeric studies of purine and alpha L alanine with an innovative sampling technique.'. AB - IR spectra claimed [Spectrochim. Acta A 55 (1999) 2329] to be those of NH2CHMeCO2H and N(7)H purine, as isolated molecules in KBr. are those of cationic species formed in the acid media used. PMID- 11765800 TI - Comparison of closely related orthopoxvirus isolates by random amplified polymorphic DNA and restriction fragment length polymorphism analysis. AB - The reliability and reproducibility of random amplified polymorphic DNA analysis (RAPD) was compared with restriction fragment length polymorphism (RFLP) by analysing three virus strains isolated from zoo animals in Berlin and three isolates which were cultivated from pets from Northern Germany. The RAPD technique was evaluated as a reliable tool with good reproducibility of the patterns for each virus strain investigated. Problems of interpretation due to inconsistent intensity of bands in different polymerase chain reaction runs may arise for less experienced personnel. The RAPD analysis can be performed within one working day and needs less DNA compared with RFLP so costs will be reduced. The obvious advantage of RFLP is that the pattern can be traced to the recognition site of the restriction enzyme whereas the RAPD primer sequence is not present in the orthopoxvirus genome at all. To the authors knowledge, the RAPD technique has never been applied in DNA viruses before and they conclude that this technique is a useful tool for the discrimination of closely related cowpoxviruses. PMID- 11765799 TI - Characterization of necrotoxigenic Escherichia coli (NTEC) strains isolated from healthy calves in Poland. AB - Faecal samples from 132 healthy, 4-8-week-old calves from four different farms were examined for necrotoxigenic Escherichia coli (NTEC) producing the cytotoxic necrotizing factors type 1 (CNF1) and type 2 (CNF2). CNF2 genes were detected by polymerase chain reaction in 24 (6.1%) of the 396 E. coli strains tested; these strains were found in 18 (13.6%) calves used in the study. None of the 396 E. coli isolates examined possessed the gene encoding CNF1. Overall, 28.8% of E. coli examined expressed the F17 fimbrial antigen. A strong association between CNF2 toxin and F17 fimbriae was found (62.5% of CNF2-positive strains were F17 positive). Moreover, six out of 24 NTEC strains had the Stx1 or the Stx2 shiga toxin genes, and three additional isolates possessed the eae genetic marker of the intimin protein. PMID- 11765801 TI - Efficacy of tilmicosin phosphate (Pulmotil premix) in feed for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing finishing pigs. AB - A double-blind randomized clinical trial was carried out to investigate the efficacy of tilmicosin (Pulmotil premix) for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing-finishing pigs. The effects of tilmicosin administration in the feed at 400 mg/kg and an injection therapy of clinically diseased pigs with long-acting oxytetracycline (Terramycine LA) at 20 mg/kg bodyweight were compared. Both groups, totalling 147 pigs, were compared during a medication period of 15 days and a post-medication period of 11 days by means of different clinical and performance parameters. During the medication period, the tilmicosin group showed a significant advantage with respect to the number of new disease cases (P < 0.01), and a non-significant advantage regarding the number of removed pigs (P = 0.16), the number of sick pigs that recovered (P = 0.27) and the time to recovery (P = 0.42). During the post-medication period, the pigs of the tilmicosin group showed numerical non significant benefits (P > 0.05) with respect to the clinical parameters. During the overall study period (26 days), the average daily gain and the feed conversion ratio were both significantly (P < 0.01) better in pigs from the tilmicosin group compared with pigs from the oxytetracycline group. This study demonstrated that in-feed medication of tilmicosin at a dosage of 400 mg/kg is efficacious for the treatment of a clinical respiratory disease outbreak of A. pleuropneumoniae infection in growing-finishing pigs. Compared with oxytetracycline injection of clinically diseased pigs, the tilmicosin treatment is particularly beneficial in the prevention of new disease cases while increasing or maintaining the performance of the pigs. PMID- 11765802 TI - Pattern of Eimeria oocyst output and repeatability in naturally infected suckling Rhon lambs. AB - The faeces of 14 Rhon lambs were examined every second day between 7 and 99 days of age for the presence of Eimeria oocysts. Eimeria absata, E. bakuensis, E. faurei, E. granulosa, E. intricata, E. ovinoidalis, E. pallida, E. parva and E. crandallis/weybridgensis were identified. The predominant species were E. ovinoidalis, E. parva, E. crandallis/weybridgensis and E. bakuensis. Using a statistical model, the oocyst excretion rate was described as a sequence of periods with decreasing levels and varying length ('excretion periods') interrupted by intervals with no or very low oocyst counts. Several variables could be deduced from these two parameters, including the length of an excretion period and the maximum output during an excretion period. Thc estimated repeatability for oocyst counts for the different species ranged from 0.05 to 0.41. This result provides a starting point for possible genetic selection based on faecal oocyst counts of Rhon sheep for resistance to Eimeria infections. PMID- 11765803 TI - Field study on the efficacy of two different vaccination schedules with HYORESP in a Mycoplasma hyopneumoniae-infected commercial pig unit. AB - A trial was carried out with HYORESP a Mycoplasma hyopneumoniae (M. hyo) vaccine in order to confirm the benefit of vaccination under field conditions in a commercial industrial farrow-to-finish unit, contaminated with M. hyo. Infection with M. hyo was confirmed through positive blood and colostrum samples [enzyme linked immunosorbent assay (ELISA) test] combined with positive gross lesions of the lung at slaughter. Two different vaccination schedules were tested. Pigs were randomly allocated to three groups: control non-vaccinated group (n = 130, given a placebo injection at 3, 25 and 70 days of age); early vaccinated group (n = 128, given vaccination at 3 and 25 days of age and a placebo at 70 days of age); late vaccinated group (n = 132, given a placebo at 3 and 25 days of age and vaccination at 70 days of age). Both growth rate and feed conversion ratio were signifcantly (P < 0.05) improved in the vaccinated groups compared with the control group. The lung lesion score was also significantly (P < 0.05) improved in both vaccinated groups. In this trial, it was clearly demonstrated that vaccination is highly effective in improving performance in pig units infected with M. hyo. The improvement in the feed conversion ratio in the vaccinated groups was especially impressive: -0.411 (13% improvement) in the group vaccinated twice at 3 and 25 days of age; -0.162 (5% improvement) in the group vaccinated once at 70 days of age. Performances were better when two shots were given early in life compared with one shot later--probably due to an infection taking place rather early in life for most of the pigs. Moreover, a significant reduction in the cost of supportive (injectable) medication was noticed in vaccinated pigs. In conclusion, HYORESP proved to be a very efficacious tool to control M. hyo in infected herds with its remarkable flexibility that allows the vaccination schedule to be adapted to the specific field conditions. PMID- 11765804 TI - Occurrence of an invertebrate iridescent-like virus (Iridoviridae) in reptiles. AB - Viral isolates were obtained in 1998, 1999 and 2000 from the lung, liver and intestine of two bearded dragons (Pogona vitticeps) and a chameleon (Chamaeleo quadricornis) and from the skin of a frill-necked lizard (Chamydosaurus kingii) by using viper heart cells (VH2) at 28 degrees C. Electron microscopic examination of infected VH2 cells revealed the assembly of icosahedral iridovirus like particles measuring 139 nm (side to side) and 151 nm (apex to apex). Negatively stained virus particles had dimensions of 149 nm (side to side) and 170 nm (apex to apex). Polymerase chain reaction (PCR) amplification of purified viral DNA with primers corresponding to the partial gene encoding the major capsid protein (MCP) of Frog viris-3 (FV-3), the type species of the genus Ranavirus, was unsuccessful. In contrast, primers corresponding to the partial MCP gene of Chilo iridescent virus (CIV; genus Iridovirus) amplified 500-bp products with 97% identity to the nucleotide sequence of CIV and 100% identity to the nucleotide sequence of Gryllus bimaculatus iridescent virus (GbIV), an invertebrate iridescent virus. Virus protein profiles analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and restriction fragment length profiles of purified viral DNA treated with the endonucleases EcoRI, HindIII and HpaII were identical to those of GbIV. PMID- 11765805 TI - Molecular differentiation of Mycoplasma gallisepticum and Mycoplasma imitans strains by pulsed-field gel electrophoresis and random amplified polymorphic DNA. AB - Pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD) analysis were used to compare 21 Mycoplasma gallisepticum strains and five M. imitans strains. Each strain of M. gallisepticum typed by PFGE and RAPD methods was genetically quite unique and RAPD and PFGE fingerprinting enabled strain characterization. Relationships between the M. gallisepticum and M. imitans strains were established and dendrograms were drawn from PFGE and RAPD patterns. PFGE group A and RAPD group D were significantly associated with M. imitans strains (P < 0.05). Three M. imitans strains shared the same PFGE and RAPD patterns. The two M. gallisepticum vaccine strains had singular PFGE and RAPD patterns. Thus, PFGE and RAPD can be used to investigate disease outbreaks in vaccinated flocks or for epidemiological tracking. For M. gallisepticum, the RAPD and PFGE discriminatory powers were superior to 0.95 and the in vitro, in ovo and in vivo reproducibility of RAPD and PFGE was 100%. The RAPD drawback was the inconsistent band intensity complicating the interpretation of patterns, while the PFGE limit was its low typeability (86%). Thus, these two molecular typing methods seemed complementary for M. gallisepticum epidemiological studies. PMID- 11765806 TI - Informative value of an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of bovine viral diarrhoea virus (BVDV) antibodies in milk. AB - Bulk and individual milk samples from 117 herds located in Brittany (west France) were used to assess: (i) the performance characteristics of an indirect enzyme linked immunosorbent assay (ELISA) applied to individual milk for the detection of antibodies to bovine viral diarrhoea virus (BVDV); and (ii) the relationship between the bulk milk result obtained from this test and the within-herd prevalence of antibody-positive lactating cows. This ELISA test was based on a monoclonal antibody directed against non-structural protein NS2-3 of pestiviruses. At the individual level, based on 1113 matched milk/serum samples, the sensitivity and specificity of this test applied to milk, compared with the virus neutralization test on serum, were 95.0 and 97.7%, respectively. At the herd level, the relationship between the optical density percentage (OD%) of bulk milk and the within-herd prevalence of antibody-positive lactating cows was assessed using the receiver operating characteristics (ROC) analysis. Classes of OD% of bulk milk were determined so that they were associated with minimum intraclass and maximum between-class variances of within-herd prevalence of antibody-positive cows. The ROC analysis resulted in two classes of bulk milk results corresponding to different expected levels of within-herd prevalence. Herds with an OD% of bulk milk < 75% and > or = 75% had a mean observed prevalence of antibody-positive cows of 8.9 and 60.6%, respectively. Herds with a bulk milk result < 75% were expected to be BVDV free, whereas large variations in prevalence of antibody-positive cows existed in the herds with OD% > or = 75%. The test described in this study is suitable to identify herds likely to have a low prevalence of BVDV antibody-positive cows. PMID- 11765807 TI - First isolation of rotavirus associated with neonatal diarrhoea in guanacos (Lama guanicoe) in the Argentinean Patagonia region. AB - Group A rotavirus (RV) and coronavirus (CV) are common viral pathogens associated with neonatal diarrhoea in numerous animal species. The purpose of this work was to investigate the presence of these viral agents in two farm populations of captured guanacos (Lama guanicoe) in the Argentinean Patagonia region, that developed severe diarrhoea outbreaks. Stool and serum samples were analysed for RV and bovine CV antigen and antibody enzyme-linked immunosorbent assay. Rotavirus was detected in faeces from two new-born guanacos with acute diarrhoea, one in each farm. After electrophoretic analysis, each isolated strain, showed a distinctive long dsRNA electropherotype characteristic of group A rotaviruses (4:2:3:2). In addition, 95% (38 of 40) of the sampled animals were positive for RV antibodies, suggesting a high prevalence of RV infection in the populations tested. No evidence of CV circulation by antigen or antibody analysis was observed. To our knowledge, this is the first report of the detection and isolation of RV associated with neonatal diarrhoea in Lama guanicoe. PMID- 11765808 TI - Evaluation of an enzyme-linked immunosorbent assay for determination of porcine haptoglobin. AB - An enzyme-linked immunosorbent assay for quantification of haptoglobin in porcine serum was evaluated. The detection limit when expressed as the estimated concentration of a blank sample was 0.0003 mg/ml. The precision of the assay was acceptable with intra-assay coefficients of variation below 4% and inter-assay coefficient of variation below 5% for serum concentrations ranging from 1.0 mg/ml and above. For samples with a concentration below 0.8 mg/ml, the inter-assay coefficient of variation was above 10% The assay maintained linearity under dilution. Recovery was proportional. Haemolysis significantly decreased the measured concentration of haptoglobin in paired serum samples (one-sided t-test, P < 0.0001, degrees of freedom = 29). No significant effect on the concentration due to repeated freezing and thawing of serum was observed. The biological variation in individual pigs with no clinical signs of disease was estimated by nested analysis of variance. Between-pig variation was 86.0% within-pig variation was 13.3% and analytical variation was 0.7%. The one-sided critical difference was 12.3% and the two-sided critical difference was 14.6%. The index of individuality was 0.2. The maximum allowable analytical imprecision was 2.6% and the maximum analytical inaccuracy was 9.9%. The number of samples required to determine the true haptoglobin value in an individual pig when accounting for the day-to-day fluctuation was 5. In conclusion, the haptoglobin assay was found to be suitable for quantification of haptoglobin in non-haemolysed porcine serum samples with a haptoglobin concentration above 1.0 mg/ml. The analytical variance was found to be low. The haptoglobin concentration in serum was found to characterize individual animals. A large inter-animal variation in haptoglobin level was found. PMID- 11765809 TI - Effect of medetomidine on electroencephalography and use of a quantitative electroencephalograph for evaluating sedation levels in dogs. AB - This study was designed to characterize the effect of medetomidine (Med) on canine electroencephalography (EEG), to evaluate the use of quantitative EEG for assessing sedation levels and to explore the correlation between the serum concentration of Med and the quantitative EEG. Four groups of dogs were given Med at doses of 20, 40, 80 and 160 microg/kg (Med-20, Med-40, Med-80 and Med-160 groups). Following Med administration, there was synchrony between each unipolar EEG lead. On EEG power spectrum analysis of the bipolar leads, all groups showed a significant depression of the 14-30 Hz components. The power of the 1-3 Hz component in the Med-80 and Med-160 groups was significantly increased, although there were few changes in the other groups. Similar results were obtained from raw data analysis. As a result of quantitative EEG analysis, spectrum edge frequency 90 analysis (SEP90) showed that the frequency was significantly reduced in all groups after Med administration. A dose-response effect was observed in all groups except for the Med-160 group. Both of these EEG analyses were significantly correlated with the serum concentration of Med. However, the result of the SPF90 analysis sugested a stronger correlation than that for median edge frequency analysis. In conclusion, care must be taken in veterinary clinical diagnoses when Med is used during EEG recording, as Med may cause increased activity in the low frequency band and a decrease in high frequency band activity. In addition, quantitative EEG analysis may be useful in assessing the depth of sedation and in further studies on Med administration. PMID- 11765810 TI - Effects of D-penicillamine on urinary copper excretion in high-copper supplemented sheep. AB - The effects of a single oral application of D-penicillamine (DPA, mean dosage 28 mg/kg body weight) on urinary copper (Cu) excretion and general renal function in six high-Cu supplemented sheep (Cu intake of 3.7 mg/day per kg body weight for 84 days) and four controls (Cu intake of 0.16 mg/day per kg body weight) were investigated to quantify induced cupruresis and the therapeutic effect of DPA as a decoppering agent. Changes in liver Cu concentration were examined before and after DPA treatment by liver biopsies. The influence of DPA treatment on general renal function was low. A 10-fold increase in renal Cu excretion was induced in both groups of sheep. Maximal Cu excretion was observed 4 h after DPA treatment, with mean values of 280 pmol/min per kg body weight in the high Cu group and 145 pmol/min per kg body weight in the controls. In the high Cu sheep, urinary Cu excretion within 24 h after DPA application was equivalent to only 0.42 +/- 0.26% of liver Cu content (mean concentration 347 +/- 124 mg/kg wet weight). Moreover, no effect of DPA on liver Cu concentration was evident. These findings demonstrate that a single application of DPA is not effective in inducing sufficient Cu loss from the bodies of Cu-loaded sheep. PMID- 11765811 TI - Factors influencing the occurrence of thrombophlebitis after post-surgical long term intravenous catheterization of colic horses: a study of 38 cases. AB - Thrombophlebitis is a well-known complication of the use of long-term in-dwelling catheters. In humans, catheter material has been shown to strongly influence the occurrence of thrombophlebitis. In the horse, the influence of catheter material has been studied in healthy experimental animals, but information on the relative importance of this factor is lacking. To investigate which factors have most impact on the frequency of jugular vein thrombosis in post-surgical colic horses, a clinical study was performed on 38 animals. Horses were randomly divided into two groups. In one group a polytetrafluoroethylene catheter was used, in the other a polyurethane catheter. Both groups were clinically monitored and screened for signs of thrombophlebitis. Seven out of 38 horses developed thrombophlebitis. The type of catheter material used had no influence on thrombophlebitis development. Dwell time was significantly longer in horses that developed thrombophlebitis compared with those that did not. There was no relationship between the occurrence of thrombophlebitis and underlying disease or surgical treatment, suggesting that the general state of debilitation these horses experienced was the most important determinant for the development of thrombophlebiris. This was further stressed by the fact that seven horses developed thrombophlebitis of the contralateral vein that had been used for the induction of anaesthesia (this incidence is much higher than in horses anaesthetized for elective surgery). It is concluded that the state of debilitation is the most important determining factor for the occurrence of thrombophlebitis after the use of long-term in-dwelling intravenous catheters. This makes a substantial reduction of the incidence of thrombophlebitis difficult, but some progress can be made by consequently restricting dwell time. PMID- 11765812 TI - Comparison of the clearance of 99mTechnetium-DTPA from the lung and lung function indices derived from the single breath diagram for carbon dioxide in horses with chronic obstructive pulmonary disease. AB - The elimination of carbon dioxide from the lung can be used to monitor ventilation and perfusion, and 99mtechnetium-diethylenetriaminepentaacetate (99mTc-DTPA) clearance is a highly sensitive index of alveolar epithelial integrity, which is a presupposition for effective gas exchange. The aim of this study was to determine whether a correlation exists between indices of lung function derived from the single breath diagram for CO2, and 99mTc-DTPA clearance in horses with chronic obstructive pulmonary disease. The rate of 99mTc-DTPA elimination was negatively and substantially correlated with the dead space according to Bohr's formula, and the physiological and alveolar dead space. Strong and significant correlations existed between the three dead space indices and the alveolar fraction of CO2, and the ratio A1/A2 as an index of alveolar efficiency. The associations found were dependent on the clinical status of health and the mode of calculation of 99mTc-DTPA alveolar clearance. PMID- 11765813 TI - Plasma gastrin activity and the diagnosis of bleeding abomasal ulcers in cattle. AB - The present study was designed to evaluate the usefulness of plasma gastrin determinations as a diagnostic aid and to review the clinical and haematological findings in cattle with bleeding abomasal ulcers. Twenty-nine cows with bleeding abomasal ulcers and six healthy cows were used. Clinical and laboratory examinations, including plasma gastrin levels, were performed. Anorexia, depression, dark-coloured to black faeces, pale mucous membranes, abdominal pain, moderate tachycardia and tachypnoca were the most pronounced clinical symptoms in the cattle with bleeding abomasal ulcers. Plasma gastrin concentration was significantly higher (P < 0.05) in the cattle with bleeding abomasal ulcers than in healthy cows. The mean plasma gastrin concentration in healthy cattle was 103.2 pg/ml, while the mean plasma gastrin concentrations in cattle with bleeding abomasal ulcers were found to be 213.6 pg/ml. Haemoglobin levels, packed cell volume, total white blood cell count and mean corpuscular volume were significantly lower (P < 0.05) in the cows with bleeding abomasal ulcer than in the healthy cattle. The results of this study show that measurement of plasma gastrin can be useful in the diagnosis of bleeding abomasal ulcers in cattle. PMID- 11765814 TI - The influence of parenterally administered alpha-tocopheryl acetate to sows on the vitamin E status of the sows and suckling piglets and piglets after weaning. AB - The main aim of the study was to test if parenteral administration of alpha tocopheryl acetate twice before farrowing and weaning could increase the vitamin E status of the newborn piglets and piglets after weaning. In Trial I eight sows were given 1.5 g alpha-tocopheryl acetate intramuscularly 7 and 2 days before farrowing. Eight sows were untreated controls. The experimental sows had a higher vitamin E concentration in colostrum than the controls. No significant difference between the groups existed in milk at weaning. The serum vitamin E concentration in the experimental piglets 2 and 5 days after farrowing was higher than in the controls. Fifteen days after farrowing the difference between the groups had nearly disappeared. The serum vitamin E concentration in the piglets in the control group was higher during the first days after farrowing than later, and was gradually reduced until at least 2 weeks after weaning. In Trial II, eight sows were given 1.5 g of alpha-tocopheryl acetate 7 and 2 days before weaning of their piglets. They had higher vitamin E concentrations in milk and serum than untreated control sows at weaning. The increase did not, however, influence the serum vitamin E concentration of the piglets. The lowest concentration of vitamin E in serum of the piglets was reached at 45 days after farrowing. The activity of the selenium-dependent enzyme glutathione peroxidase in the serum of piglets was very low during the first week of life in both groups despite the fact that the sows' feed had been supplemented with 0.35 mg selenium/kg. This indicates that the selenium status of newborn piglets might be more critical for their health than their vitamin E status. PMID- 11765815 TI - Convection-enhanced delivery in intact and lesioned peripheral nerve. AB - OBJECT: Although the use of multiple agents is efficacious in animal models of peripheral nerve injury, translation to clinical applications remains wanting. Previous agents used in trials in humans either engendered severe side effects or were ineffective. Because the blood-central nervous system barrier exists in nerves as it does in the brain, limited drug delivery poses a problem for translation of basic science advances into clinical applications. Convection enhanced delivery (CED) is a promising adjunct to current therapies for peripheral nerve injury. In the present study the authors assessed the capacity of convection to ferry macromolecules across sites of nerve injury in rat and primate models, examined the functional effects of convection on the intact nerve, and investigated the possibility of delivering a macromolecule to the spinal cord via retrograde convection from a peripherally introduced catheter. METHODS: The authors developed a rodent model of convective delivery to lesioned sciatic nerves (injury due to crush or laceration in 76 nerves) and compared the results to a smaller series of five primates with similar injuries. In the intact nerve, convective delivery of vehicle generated only a transient neurapraxic deficit. Early after injury (postinjury Days 1, 3, 7, and 10), infusion failed to cross the site of injury in crushed or lacerated nerves. Fourteen days after crush injury, CED of radioactively-labeled albumin resulted in perfusion through the site of injury to distal growing neurites. In primates, successful convection through the site of crush injury occurred by postinjury Day 28. In contrast, in laceration models there was complete occlusion of the extracellular space to convective distribution at the site of laceration and repair, and convective distribution in the extracellular space crossed the site of injury only after there was histological evidence of completion of nerve regeneration. Finally, in two primates, retrograde infusion into the spinal cord through a peripheral nerve was achieved. CONCLUSIONS: Convection provides a safe and effective means to deliver macromolecules to regenerating neurites in crush-injured peripheral nerves. Convection block in lacerated and suture-repaired nerves indicates a significant intraneural obstruction of the extracellular space. a disruption that suggests an anatomical obstruction to extracellular and, possibly, intraaxonal flow, which may impair nerve regeneration. Through peripheral retrograde infusion, convection can be used for delivery to spinal cord gray matter. Convection-enhanced delivery provides a promising approach to distribute therapeutic agents to targeted sites for treatment of disorders of the nerve and spinal cord. PMID- 11765816 TI - Site-specific immune response to implanted gliomas. AB - OBJECT: Immunotherapy for glioblastoma has been uniformly ineffective. The immunological environment of the brain, with its low expression of major histocompatibility complex (MHC) molecules and limited access for inflammatory cells and humoral immune effectors due to the blood-brain barrier (BBB), may contribute to the failure of immunotherapy. The authors hypothesize that brain tumors are protected from immune surveillance by an intact BBB at early stages of development. To investigate the immunological characteristics of early tumor growth, the authors compared the host response to a glioma implanted into the brain and into subcutaneous tissue. METHODS: Samples of tumors growing in the brain or subcutaneously in rats were obtained for 7 consecutive days and were examined immunohistochemically for MHC Class I & II molecules, and for CD4 and CD8 lymphocyte markers. Additionally, B7-1 costimulatory molecule expression and lymphocyte-specific apoptosis were examined. CONCLUSIONS: On Days 3 and 4 after implantation, brain tumors displayed significantly lower MHC Class II expression and lymphocytic infiltration (p < 0.05). After Day 5, however, no differences were detected. The MHC Class II expressing cells within the brain tumors appeared to be infiltrating microglia. Minimal B7-1 expression combined with lymphocyte specific apoptosis were detected in both brain and subcutaneous tumors. Low MHC Class II expression and low lymphocytic infiltration at early time points indicate the importance of the immunologically privileged status of the brain during early tumor growth. These characteristics disappeared at later time points, possibly because the increasing perturbation of the BBB alters the specific immunological environment of the brain. The lack of B7-1 expression combined with lymphocyte apoptosis indicates clonal anergy of glioma-infiltrating lymphocytes regardless of implantation site. PMID- 11765817 TI - Intraaneurysmal flow dynamics study featuring an acrylic aneurysm model manufactured using a computerized tomography angiogram as a mold. AB - OBJECT: To obtain precise flow profiles in patients' aneurysms, the authors developed a new in vitro study method featuring an aneurysm model manufactured using three-dimensional computerized tomography (3D CT) angiography. METHODS: A clear acrylic basilar artery (BA) tip aneurysm model manufactured from a patient's 3D CT angiogram was used to analyze flow modifications during one cardiac cycle. Stereolithography was utilized to create the aneurysm model. Three dimensional flow profiles within the aneurysm model were obtained from velocity measurements by using laser Doppler velocimetry. The aneurysm inflow/outflow zones changed dynamically in their location, size of their cross-sectional area, and also in their shapes over one cardiac cycle. The flow velocity at the inflow zone was 16.8 to 81.9% of the highest axial velocity in the BA with a pulsatility index (PI) of 1.1. The flow velocity at the outflow zone was 16.8 to 34.3% of the highest axial velocity of the BA, with a PI of 0.68. The shear stress along the walls of the aneurysm was calculated from the fluid velocity measured at a distance of 0.5 mm from the wall. The highest value of shear stress was observed at the bleb of the aneurysm. CONCLUSIONS: This clear acrylic model of a BA tip aneurysm manufactured using a CT angiogram allowed qualitative and quantitative analysis of its flow during a cardiac cycle. Accumulated knowledge from this type of study may reveal pertinent information about aneurysmal flow dynamics that will help practitioners understand the relationship among anatomy, flow dynamics, and the natural history of aneurysms. PMID- 11765818 TI - Hearing restoration with auditory brainstem implants after radiosurgery for neurofibromatosis type 2. AB - The auditory brainstem implant (ABI) is designed to restore useful auditory sensations in patients with neurofibromatosis Type 2 (NF2). The implantation is usually performed at the time of tumor removal in patients who do not undergo radiation treatment. The authors evaluated the performance of ABIs in three patients with NF2 in whom vestibular schwannoma continued to grow after radiation treatment. These three patients with NF2 received a 21-channel ABI; a translabyrinthine approach was used for both the tumor removal and the ABI placement. The interval between radiosurgery and the tumor removal plus device implantation ranged from 2 to 11 years. In all cases, the tumor was growing and the patients presented with total deafness. The mean number of active electrodes in these three patients was equivalent to the average results reported in other patients who received ABIs. The patients in this study used the ABI regularly for everyday life and obtained useful levels of environmental sound recognition. It is concluded that hearing function can be rehabilitated using ABIs in patients with NF2, even if radiosurgery fails to control the tumor growth. PMID- 11765819 TI - Atypical hemifacial microsomia associated with Chiari I malformation and syrinx: further evidence indicating that chiari I malformation is a disorder of the paraaxial mesoderm. Case report and review of the literature. AB - The authors present the first known reported case of hemifacial microsomia associated with a Chiari I malformation and syrinx. A 14-year-old girl presented with progressive torticollis of 3 years' duration and headaches exacerbated by exercise. Computerized tomography scanning and magnetic resonance imaging revealed extensive craniofacial and vertebral abnormalities, including aplasia of the floor of the left middle fossa and posterior fossa cranium, articulation of the left mandibular condyle with the left temporal lobe, and progressive development of a Chiari I malformation with associated syringomyelia. The patient first underwent posterior fossa decompression, duraplasty, and occipitocervical fusion. This procedure was later followed by reconstruction of the floor of the left middle fossa and temporomandibular joint. The patient's outcome was excellent. In this case report the authors review the complex embryological development of craniofacial and craniovertebral structures, and emphasize the use of a staged approach to treat pathophysiological consequences of this congenital anomaly. PMID- 11765820 TI - Choroid plexus carcinoma presenting as an intraparenchymal mass. AB - A 6-year-old girl with a history of a nondisplaced skull fracture diagnosed with computerized tomography (CT) scanning 3 years previously presented with a 6-week history of headaches and decreased use of her right side. On admission CT scans, a large cystic mass was identified in the left frontal lobe region of the brain. A connection between the mass and the ventricular system was not seen on radiological examination or during surgery. Gross-total resection of the mass was achieved. The histological and immunohistochemical findings in the resected tissue confirmed a diagnosis of choroid plexus carcinoma (ChPC). This is the first reported case of a ChPC arising in an extraventricular location not associated with the choroid plexus. PMID- 11765821 TI - Fibrous meningioma in a patient with von Hippel-Lindau disease: a genetic analysis. AB - Meningioma has been included in the constellation of tumors associated with von Hippel-Lindau (VHL) disease in previously published reports. It is unclear whether these tumors are an uncommon component of VHL disease or are more readily detected in these patients because of the frequency with which they undergo central nervous system imaging as part of the routine management of VHL disease. The authors report the case of a patient with VHL disease in whom a progressively enlarging supratentorial mass developed and was diagnosed as a hemangioblastoma because of its appearance on serial magnetic resonance images. At surgery the tumor displayed the typical features of a meningioma and was given the histological diagnosis of fibrous meningioma. Single-stranded conformational polymorphism analysis of the tumor DNA revealed a loss of heterozygosity at the neurofibromatosis Type 2 gene locus, known to be associated with sporadically occurring meningiomas. Despite this finding, the VHL gene locus on the allele from the patient's unaffected parent was normal. Thus it is unlikely that the occurrence of this patient's fibrous meningioma was associated with underlying VHL disease. Given the high frequency of neuroimaging sessions in patients with VHL disease, some supratentorial lesions that have been given radiological diagnoses of hemangioblastomas may be incidental meningiomas. PMID- 11765822 TI - Recovery from complete hemiplegia following resection of a retrocentral metastasis: the prognostic value of intraoperative cortical stimulation. AB - The goal in this study was to determine if intraoperative electrical stimulation mapping is useful during surgical resection of lesions located in the central region, even in cases of preoperative hemiplegia. This 45-year-old man with a retrocentral metastasis from an embryonal carcinoma of the testis suffered an acute complete hemiplegia after intratumoral bleeding. Emergency surgery was performed with the aid of intraoperative motor mapping despite the preoperative deficit. Cortical stimulations (CSs) elicited motor responses, allowing the detection and hence preservation of the primary motor area during tumor removal. Postoperatively, the patient recovered almost completely within 1 week; the tumor resection was total. It is possible that CSs give an early and valuable prognostic indicator of motor recovery in cases of complete hemiplegia, at least in patients with acute onset and short duration of the deficit. Consequently, if motor responses can be elicited by CSs, it becomes mandatory for the surgeon to respect the primary motor area despite the preoperative hemiplegia, with the aim of preserving the chances of an eventual recovery. PMID- 11765823 TI - Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion. AB - The authors present the hospital course of a 13-year-old girl with a closed head injury who received a prolonged infusion of propofol for sedation and, subsequently, died as a result of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse. The patient had been treated for 4 days at a referring hospital for a severe closed head injury sustained in a fall from a bicycle. During treatment for elevations of intracranial pressure, she received a continuous propofol infusion (100 microg/kg/min). The patient began to exhibit severe high anion gap/low lactate metabolic acidosis, and was transferred to the pediatric intensive care unit at the authors' institution. On arrival there, the patient's Glasgow Coma Scale score was 3 and this remained unchanged during her brief stay. The severe metabolic acidosis was unresponsive to maximum therapy. Acute renal failure ensued as a result of rhabdomyolysis, and myocardial dysfunction with bizarre, wide QRS complexes developed without hyperkalemia. The patient died of myocardial collapse with severe metabolic acidosis and multisystem organ failure (involving renal, hepatic, and cardiac systems) approximately 15 hours after admission to the authors' institution. This patient represents another case of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse observed after a prolonged propofol infusion in a pediatric patient. The authors suggest selection of other pharmacological agents for long-term sedation in pediatric patients. PMID- 11765824 TI - Anaglyphic three-dimensional stereoscopic printing: revival of an old method for anatomical and surgical teaching and reporting. AB - The authors describe how to use the three-dimensional (3D) anaglyphic method to produce stereoscopic prints for anatomical and surgical teaching and reports preparation by using currently available nonprofessional photographic and computer methods. As with any other method of producing stereoscopic images, the anaglyphic procedure is based on the superimposition of two slightly different images of the object to be reproduced, one seen more from a left-sided point of view and the other seen more from a right-sided point of view. The pictures are obtained using a single camera, which following the first shot can be slid along a special bar for the second shot, or by using two cameras affixed to a surgical microscope. After the images have been distinguished from each other by applying different complementary color dyes, the images are scanned and superimposed on each other with the aid of nonprofessional imaging-manipulation software used on a standard personal computer (PC), and are printed using a standard printer. To be seen stereoscopically, glasses with colored lenses, normally one red and one blue, have to be used. Stereoscopic 3D anaglyphic prints can be produced using standard photographic and PC equipment; after some training, the prints can be easily reproduced without significant cost and are particularly helpful to disclose the 3D character of anatomical structures. PMID- 11765825 TI - An MKM-mounted instrument holder for frameless point-stereotactic procedures: a phantom-based accuracy evaluation. AB - To enable the use of the Mehrkoordinaten Manipulator (MKM) robotic navigation system for frameless point stereotactic procedures, a new instrument holder is presented. A phantom-based accuracy study was performed in which this new method was compared with frame-based procedures performed using the Brown-Roberts-Wells (BRW) stereotactic frame. The authors acquired computerized tomography scans of a test phantom, consisting of 19 acrylic plastic target rods on a circular base. These images were used in frame-based (BRW) and frameless (MKM) localization experiments. In both cases the authors calculated the distances between the actual target positions and the positions reached stereotactically. The mean application accuracy (target registration error) was 0.68 mm when the BRW frame was used and 0.96 mm when the MKM system was used after manual repositioning of the microscope (p < 0.001). Positioning accomplished using robotics only demonstrated a slightly larger inaccuracy: 1.47 mm (p < 0.005). Because the surgeon is concerned with the largest error in an individual case rather than the mean error in a large number of cases, the mean + three standard deviations was also compared. This value differed very little between the manually positioned MKM system and the BRW frame (2.04 mm and 1.84 mm, respectively). Although repeatability per target appeared to be slightly better when the BRW frame was used, accuracy was more homogeneous over the phantom volume when the MKM system was used (both differences were not significant). In conclusion, the accuracy of point stereotactic procedures performed using an instrument holder attached to the system is comparable with the accuracy of procedures involving a stereotactic frame. Moreover, the frameless techniques and robotic features of the MKM enable a more surgeon- and patient-friendly stereotactic procedure. PMID- 11765827 TI - Double-barreled tack suture procedure in carotid endarterectomy. AB - The authors have developed a double-barreled tack suture procedure for carotid endarterectomy with minimal modification of a conventional needle holder. With this method surgeons can make two stitches simultaneously by using two needles threaded with double-armed suture material, which are held tightly in a parallel fashion in the jaws of a modified needle holder. This method is very effective in preventing the buckling of the intimal wall of the arterectomized distal internal carotid artery. Also, it reduces the tack suture time markedly compared with the conventional tack suture method. PMID- 11765826 TI - New method of deep brain stimulation therapy with two electrodes implanted in parallel and side by side. AB - Reversibility and adaptability are preferred features of long-term therapeutic deep brain stimulation (DBS). In such therapy, a permanent stimulating electrode with four contact points is placed at the stimulation site and, generally speaking, bipolar stimulation is induced by various pairs of adjacent contact points on one electrode. The stimulation sites are thus all located along the trajectory of the implanted electrode. In a patient with unilateral severe essential tremor, the authors implanted two electrodes side by side and parallel to each other in the unilateral thalamic ventralis intermedius nucleus. Using these electrodes, the authors were able to deliver current flow not only along the electrode trajectory, but also between the two electrodes in a direction parallel to the anterior commissure-posterior commissure line. Although individual stimulations, delivered by each of the two electrodes using all parameters and all stimulation points, were unable to stop the patient's tremor completely without adverse effects, the new stimulation method, in which electrical currents passed between the two electrodes, effected complete abolition of the tremor without adverse effects. With the aid of this method, one can use two electrodes, implanted in parallel and side by side, to achieve maximum efficacy and to reduce adverse effects in some instances of DBS therapy. PMID- 11765828 TI - Multilocular cystic lesion associated with a giant aneurysm. PMID- 11765829 TI - Tumor involvement of the corticospinal tract: diffusion magnetic resonance tractography with intraoperative correlation. PMID- 11765830 TI - The history and evolution of transsphenoidal surgery. AB - Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches. Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed. PMID- 11765831 TI - Pioneers in the development of transsphenoidal surgery: Theodor Kocher, Oskar Hirsch, and Norman Dott. AB - The development of new scientific concepts and techniques is usually the result of a progressive evolution. The transsphenoidal approach to pituitary lesions is no exception. Several pioneers contributed to its development and its eventual and nearly unconditional acceptance. In this historical vignette, the contributions of three master surgeons. Theodor Kocher, Oskar Hirsch, and Norman Dott, are reviewed. PMID- 11765832 TI - Sensory ganglionectomy. PMID- 11765833 TI - Diffuse axonal injury. PMID- 11765834 TI - Pituitary abscess. PMID- 11765835 TI - Propofol-infusion syndrome. PMID- 11765836 TI - Give neurosurgery a place to stand. The 2001 presidential address. AB - In his 2001 Presidential Address to the American Association of Neurological Surgeons, Dr. Dunsker calls on all neurosurgeons to become active participants in the ongoing debates over healthcare. He reviews some history of the debates and points out that regulation of healthcare has been left to bureaucrats-both government and private-with physicians, who have intimate knowledge of the field, being excluded. Dr. Dunsker encourages neurosurgeons to volunteer in local, state, and federal medical societies and to join forces with other physicians to gain leverage in the healthcare debate. In this manner it is hoped that better ways of delivering the best healthcare to patients can be accomplished. PMID- 11765837 TI - Chordomas of the craniocervical junction: follow-up review and prognostic factors. AB - OBJECT: Chordomas are rare tumors that arise from the remnants of the notochord. Because of their deep location, local infiltrative nature, and involvement of surrounding bone, treatment of chordomas is a challenge. In this study the authors analyze the data and prognostic factors obtained during the follow-up period (range 1-150 months, median 38 months) in 53 patients with craniocervical junction chordomas and 10 patients with chondrosarcomas. METHODS: Several surgical approaches were used, and some tumor excisions required staged procedures. Survival was calculated according the Kaplan-Meier method. Statistical analysis was performed using Fisher exact, log rank and Kruskal Wallis tests. Radical/subtotal resection was achieved in 77.8% of the patients. The mortality rate during the follow-up period was 14.3%. In patients harboring chondrosarcoma better 5-year recurrence-free survival (RFS) rates were demonstrated than in those with chordoma (100% and 50.7%. respectively). Histological patterns (typical or chondroid chordomas) and patient age at onset of symptoms had no effect on the RFS rates. Radical/subtotal resections were associated with better RFS rates than partial resection. Adjuvant proton-beam therapy was shown to increase the RFS rates compared with conventional radiotherapy (90.9% and 19.4%, respectively, at 4 years posttreatment). Karyotypically abnormal tumors were associated with the worst RFS rates compared with karyotypically normal lesions (44.5% and 90.3%, respectively, at 3 years). Cases of cranial nerve palsy followed by those with cerebrospinal fluid leakages were the most frequent postoperative complications. Permanent postoperative neurological deficit was observed in 28.6% of the patients. CONCLUSIONS: A better prognosis was observed in patients with chondrosarcoma compared with those harboring chordoma. Histological pattern and patient age at symptom onset were not factors that influenced prognosis in cases of chordoma. Extensive resection and possibly adjuvant proton-beam therapy provided better prognoses for these patients. PMID- 11765838 TI - Contemporary psychosurgery and a look to the future. AB - OBJECT: Despite a long and controversial history, psychosurgery has persisted as a modern treatment option for some severe, medically intractable psychiatric disorders. The goal of this study was to review the current state of psychosurgery. METHODS: In this review, the definition of psychosurgery, patient selection criteria, and anatomical and physiological rationales for cingulotomy, subcaudate tractotomy, anterior capsulotomy, and limbic leukotomy are discussed. The historical developments, modern procedures, and results of these four contemporary psychosurgical procedures are also reviewed. Examples of recent advances in neuroscience indicating a future role for neurosurgical intervention for psychiatric disease are also mentioned. CONCLUSIONS: A thorough understanding of contemporary psychosurgery will help neurosurgeons and other physicians face the ethical, social, and technical challenges that are sure to lie ahead as modern science continues to unlock the secrets of the mind and brain. PMID- 11765839 TI - Changes in functional outcome and quality of life in patients and caregivers after aneurysmal subarachnoid hemorrhage. AB - OBJECT: Although the case-fatality rate after subarachnoid hemorrhage (SAH) does not change considerably after the first 4 weeks, functional outcome and the quality of life (QOL) may. To assess the extent of changes in functional outcome and QOL after SAH, the authors conducted a follow-up study at 18 months in patients and caregivers who had participated in a previous study of QOL 4 months after SAH. METHODS: In a consecutive series of 98 patients admitted with SAH, 68 had survived until 4 months postbleed, at which time an initial outcome assessment had been performed in 64 of them. This series of 64 patients was contacted again at a median of 18 months after SAH. In all patients, functional outcome was assessed by means of the modified Rankin Scale (mRS). In 48 patients and 35 caregivers QOL was assessed using the SF-36, the Sickness Impact Profile (SIP), and a visual analog scale. The results were compared with the scores that had been obtained at 4 months after SAH. Thirty-two patients (50%) had improved at least one point on the mRS, in 23 patients functional outcome had remained unchanged, six patients had deteriorated one point on the mRS, and three had died. No major changes in the QOL of patients and caregivers could be found on the SIP, but on the SF-36 an improved QOL was detected in patients with better Rankin grades. On both instruments, the QOL at 18 months was still reduced compared with the reference population in all patients. CONCLUSIONS: Functional outcome improves significantly between 4 months and 18 months post-SAH; studies on functional outcome after SAH can be compared only if outcome is assessed at the same time interval. The improved functional outcome seems to be accompanied by an improved QOL. PMID- 11765840 TI - Mechanisms of intracerebral hemorrhage after carotid endarterectomy. AB - OBJECT: Intracerebral hemorrhage (ICH) is an uncommon complication of carotid endarterectomy (CEA), and carries a high rate of mortality and morbidity. Traditionally, attention has been focused on the cerebral hyperperfusion syndrome (HPS) as the leading cause of ICH after CEA. Other mechanisms, such as a perioperative cerebral ischemic event, cerebral infarction, and use of postoperative anticoagulation therapy, may also be important. METHODS: The authors performed a retrospective case control study to identify factors leading to ICH after CEA. Records of CEAs performed over the past 10 years at the Mayo Clinic were searched for occurrences of ICH within 30 days of the procedure. The relationship of ICH to known cerebrovascular risk factors, perioperative electroencephalographic studies, and 133Xe cerebral blood flow (CBF) studies was compared with that in a control group. Hyperperfusion was defined as hypertension with symptoms of either severe headache, seizures, or confusion, or a doubling of intraoperative CBF values. The clinical history and imaging of ischemic events and the ICH were carefully reviewed to determine the possible underlying mechanism(s). Twelve (0.4%) of 2747 patients who underwent CEAs suffered a postoperative ICH. A doubling of CBF values was found in five of eight cases in which CBF studies were performed, and occurred more commonly in the patients with ICH than in controls. Clinical symptoms of the HPS were less common (three cases). A perioperative cerebral ischemic event (four cases) and anticoagulation therapy (six cases) were other contributors to a subsequent ICH. Seven of the 12 patients with ICHs died and five achieved a moderate outcome. CONCLUSIONS: An ICH following CEA is an unusual complication that occurs in the setting of hyperperfusion, perioperative cerebral ischemia, anticoagulation therapy, or multiple mechanisms. Identification of CBF doubling at surgery may assist in identifying patients at risk for ICH following CEA. PMID- 11765841 TI - Management of idiopathic normal-pressure hydrocephalus: a multiinstitutional study conducted in Japan. AB - OBJECT: A cooperative study was undertaken to identify factors that could be used to predict a favorable outcome after extracranial cerebrospinal fluid (CSF) diversion (shunting) in patients with suspected idiopathic normal-pressure hydrocephalus (NPH). METHODS: Questionnaires concerning patients with suspected idiopathic NPH were sent to 14 members of the Committee for Scientific Research on Intractable Hydrocephalus, sponsored by the Ministry of Health and Welfare of Japan. After the questionnaires were returned, a retrospective analysis of the responses was undertaken. To be included in the study, patients had to be 65 years of age or older and had to have undergone surgery between October 1995 and October 1998. Clinical measures included degrees of gait disturbance, dementia, and urinary incontinence as evaluated before. 3 months after, and 3 years after shunt placement. Diagnostic tests in various combinations included lumbar puncture in which CSF was withdrawn; intracranial pressure monitoring; measurements of CSF outflow resistance, level of serum alpha-1-antichymotrypsin, cerebral arteriovenous differences of oxygen content, and cerebral blood flow; and computerized tomography cisternography. In this study, 120 patients were identified as having idiopathic NPH and these patients underwent placement of shunts. A ventriculoperitoneal shunt with a programmable valve was used in two thirds of the patients. At the end of 3 months (early assessment), there was an 80% overall rate of clinical improvement, which dropped to 73.3% of the 105 patients who could be evaluated at the end of the 3-year study. Of the three variables, gait disturbance was most improved, both at early and late testing periods. Shunt complications occurred in 22 (18.3%) of the patients. CONCLUSIONS: Patients suspected of having idiopathic NPH did not form a homogeneous group, making it difficult to select those who would most likely respond to CSF diversion. Of the diagnostic studies, the most reliable result was improvement in clinical symptoms following a lumbar puncture in which CSF was withdrawn. The use of a programmable valve is recommended because it offers advantages in preventing problems of over- and underdrainage. PMID- 11765842 TI - Recording nasal muscle F waves and electromyographic activity of the facial muscles: a comparison of two methods used for intraoperative monitoring of facial nerve function. AB - OBJECT: A comparison of two electrophysiological methods used to assess facial nerve function intraoperatively was conducted in 33 patients with tumors of the cerebellopontine angle. METHODS: All 33 patients had presented with normal facial nerve function preoperatively. After general anesthesia had been induced by a mixture of midazolam and fentanyl, continual online EMG recordings from the orbicularis oculi and oris muscles were alternated with nasal muscle F-wave recordings. Facial nerve outcomes, assessed using a modified House-Brackmann scale, varied among good (48%), moderate (18%), and poor (33%). Analysis of electromyographic (EMG) data resulted in a significant correlation between the finding of only transient manipulation-evoked activity and a good outcome, whereas in cases in which there was poor outcome, an increase in the amplitude or duration of ongoing activity was detected. A permanent loss of nasal muscle F waves specifically appeared to indicate a severe dysfunction of the facial nerve that was linked to a poor outcome. All patients with latency and/or amplitude changes or even a transient loss of the F wave achieved good or moderate facial nerve outcomes. A transient loss of the F wave, however, was detected significantly more frequently in patients with moderate outcomes. None of these patients exhibited normal facial function (House-Brackmann Grade I) postoperatively. CONCLUSIONS: Online EMG monitoring can provide some information on imminent or even present damage to the facial nerve intraoperatively. The diagnostic sensitivity, specificity, and positive predictive values of a permanent F-wave loss, however, are much higher than those of EMG monitoring. Additionally, this loss of the F wave is supposed to be transient if the surgical procedure is stopped until the F wave recovers. Therefore, F-wave monitoring serves to alert the surgeon that the facial nerve is about to receive a lesion. PMID- 11765843 TI - Treatment window for hypothermia in brain injury. AB - OBJECT: The goal of this study was to evaluate the therapeutic window for hypothermia treatment following experimental brain injury by measuring edema formation and functional outcome. METHODS: Traumatic brain injury (TBI) was produced in anesthetized rats by using cortical impact injury. Edema was measured in the ipsilateral and contralateral hemispheres by subtracting dry weight from wet weight, and neurological function was assessed using a battery of behavioral tests 24 hours after TBI. In injured rats, it was found that brain water levels were elevated at I hour postinjury, compared with those in sham-injured control animals, and that edema peaked at 24 hours and remained elevated for 4 days. Hypothermia (3 hours at 30 degrees C) induced either immediately after TBI or 60 minutes after TBI significantly reduced early neurological deficits. Delay of treatment by 90 or 120 minutes postinjury did not result in this neurological protection. Immediate administration of hypothermia also significantly decreased the peak magnitude of edema at 24 hours and 48 hours postinjury, compared with that in normothermic injured control animals. When delayed by 90 minutes, hypothermia did not affect the pattern of edema formation. CONCLUSIONS: When hypothermia was administered immediately or 60 minutes after TBI, injured rats showed an improvement in functional outcome and a decrease in edema. Delayed hypothermia treatment had no effect on functional outcome or on edema. PMID- 11765844 TI - Combination of stereotactic radiosurgery and cytokine gene-transduced tumor cell vaccination: a new strategy against metastatic brain tumors. AB - OBJECT: To determine if the combination of radiosurgery and tumor cell vaccine would enhance the therapy of metastatic lesions of the central nervous system (CNS), the authors examined the antitumoral effects of radiosurgery and cytokine transduced tumor cell vaccine. METHODS: Fifty-five rats underwent intracranial implantation of 5 x 10(3) MADB 106 cells. On Day 3 after tumor implantation, 34 rats were inoculated in the flank with nonirradiated MADB 106 cells that had been retrovirally transduced to express granulocyte-macrophage colony-stimulating factor or interleukin-4. Twenty-seven rats (17 animals that had received the vaccine and 10 that had not) underwent radiosurgery performed using a gamma knife at maximum doses of 32 Gy on Day 5. No animals in the untreated group or in the vaccine-alone groups survived longer than 21 days. Animals treated by ra diosurgery alone displayed prolonged survival in comparison with untreated animals (p < 0.0001), but only one of 10 animals survived longer than 55 days. In contrast, 14 of 17 animals that received the combination therapy of radiosurgery and vaccination survived longer than 55 days (p = 0.0003 compared with animals that underwent radiosurgery alone). On Day 55, the long-term survivors were challenged by parental MADB 106 cells, which were implanted in the contralateral hemisphere. All animals from the combination therapy groups survived longer than 50 days after this challenge, but the single survivor from the radiosurgery-alone group died of tumor growth in 27 days. CONCLUSIONS: The combination of radiosurgery and cytokine gene-transduced tumor cell vaccine markedly prolonged animal survival and protected animals from a subsequent challenge by parental tumor cells placed in the CNS. The data provided by this study indicate that this combination therapy represents a strategy that may have clinical applicability for single and/or multiple metastatic brain tumors. PMID- 11765845 TI - Radiosurgery performed with the aid of a 3-mm collimator in the subthalamic nucleus and substantia nigra of the vervet monkey. AB - OBJECT: Radiosurgery for functional neurosurgery performed using a linear accelerator (LINAC) has not been extensively characterized in preclinical studies. In the present study, the properties of a newly designed 3-mm-diameter collimator were evaluated in a dedicated LINAC, which produced lesions in the basal ganglia of vervet monkeys. Lesion formation was determined in vivo in three animals by examining magnetic resonance (MR) images to show the dose-delivery precision of targeting and the geometry and extent of the lesions. Postmortem immunohistochemical studies were conducted to determine the extent of lesion induced radiobiological effects. METHODS: In three male vervet monkeys, the subthalamic nucleus (STN; one animal) and the pars compacta of the lateral substantia nigra (SN; two animals) were targeted by a Novalis Shaped Beam Surgery System that included a 3-mm collimator and delivered a maximum dose of 150 Gy. Magnetic resonance images obtained 4, 5, and 9 months posttreatment were reviewed, and the animals were killed so that immunohistological characterizations could be made. CONCLUSIONS: The generation of precise radiosurgical lesions by a 3-mm collimator was validated in studies that targeted the basal ganglia of the vervet monkey. The extent of the lesions created in all animals remained restricted in diameter (< 3 mm) throughout the duration of the studies, as assessed by reviewing MR images. Histological studies showed that the lesions were contained within the STN and SN target areas and that there were persistent increases in glial fibrillary acidic protein immunoreactivity. Increases in immunoreactivity for tyrosine hydroxylase, the serotonin transporter, and the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4 isoxazole propionate glutamate receptor in penumbral regions of the lesion were suggestive of compensatory neuronal adaptations. This radiosurgical approach may be of particular interest for the induction of lesions of the STN and SN in studies of experimental parkinsonism, as well as for the development of potential radiosurgical treatments for Parkinson disease. PMID- 11765846 TI - Surgical landmarks for the proximal portion of the axillary nerve. AB - OBJECT: The proximal segment of the axillary nerve (ANp) is often difficult to identify without extensive dissection deep into the axilla. The present study was performed to find reliable surgical landmarks for this nerve. METHODS: Thirty dissections of human cadavers were performed to determine the relationships between the ANp and specific anatomical structures. The authors found that the ANp is consistently located within an anatomical triangle constructed by lines passing between the coracobrachialis and pectoralis minor muscles and the axillary artery. In addition, the ANp was routinely found 4 cm distal to the coracoid process of the scapula. CONCLUSIONS: These findings should assist the surgeon in locating the ANp during brachial plexus reconstruction. PMID- 11765847 TI - Medical target prediction from genome sequence: combining different sequence analysis algorithms with expert knowledge and input from artificial intelligence approaches. AB - By exploiting the rapid increase in available sequence data, the definition of medically relevant protein targets has been improved by a combination of: (i) differential genome analysis (target list): and (ii) analysis of individual proteins (target analysis). Fast sequence comparisons, data mining, and genetic algorithms further promote these procedures. Mycobacterium tuberculosis proteins were chosen as applied examples. PMID- 11765848 TI - A computer system to perform structure comparison using TOPS representations of protein structure. AB - We describe the design and implementation of a fast topology-based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern-matching algorithm for TOPS diagrams that we have designed and described elsewhere (Bioinformatics 15(4) (1999) 317). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email. PMID- 11765849 TI - Predicting function from structure: examples of the serine protease inhibitor canonical loop conformation found in extracellular proteins. AB - The prediction of protein function from structure is becoming of growing importance in the age of structural genomics. We have focused on the problem of identifying sites of potential serine protease inhibitor interactions on the surface of proteins of known structure. Given that there is no sequence conservation within canonical loops from different inhibitor families we first compare representative loops to all fragments of equal length among proteins of known structure by calculating main-chain RMS deviation. Fragments with RMS deviation below a certain threshold (hits) are removed if residues have solvent accessibilities appreciably lower than those observed in the search structure. These remaining hits are further filtered to remove those occurring largely within secondary structure elements. Likely functional significance is restricted further by considering only extracellular protein domains. Also a test is performed to see if the loop can dock into the binding site of the serine protease trypsin without unacceptable steric clashes. By comparing different canonical loop structures to the protein structure database we show that the method was able to detect previously known inhibitors. In addition, we discuss potentially new canonical loop structures found in secreted hydrolases, toxins, viral proteins, cytokines and other proteins. We discuss the possible functional significance of several of the examples found. PMID- 11765850 TI - Consistent integration of non-reliable heterogeneous information resources applied to the annotation of transmembrane proteins. AB - Information agents integrate multiple distributed heterogeneous information sources. The challenging yet unsolved problem that remains, is to ensure the semantic consistency of the integrated data. In this paper we set out to develop a general approach to inconsistency management for information agents. It is implemented as part of the EDITtoTrEMBL system and applied on a large real-world problem in the domain of bioinformatics. PMID- 11765851 TI - Drug design by machine learning: support vector machines for pharmaceutical data analysis. AB - We show that the support vector machine (SVM) classification algorithm, a recent development from the machine learning community, proves its potential for structure-activity relationship analysis. In a benchmark test, the SVM is compared to several machine learning techniques currently used in the field. The classification task involves predicting the inhibition of dihydrofolate reductase by pyrimidines, using data obtained from the UCI machine learning repository. Three artificial neural networks, a radial basis function network, and a C5.0 decision tree are all outperformed by the SVM. The SVM is significantly better than all of these, bar a manually capacity-controlled neural network, which takes considerably longer to train. PMID- 11765852 TI - Application of a time-delay neural network to promoter annotation in the Drosophila melanogaster genome. AB - Computational methods for automated genome annotation are critical to understanding and interpreting the bewildering mass of genomic sequence data presently being generated and released. A neural network model of the structural and compositional properties of a eukaryotic core promoter region has been developed and its application for analysis of the Drosophila melanogaster genome is presented. The model uses a time-delay architecture, a special case of a feed forward neural network. The structure of this model allows for variable spacing between functional binding sites, which is known to play a key role in the transcription initiation process. Application of this model to a test set of core promoters not only gave better discrimination of potential promoter sites than previous statistical or neural network models, but also revealed indirectly subtle properties of the transcription initiation signal. When tested in the Adh region of 2.9 Mbases of the Drosophila genome, the neural network for promoter prediction (NNPP) program that incorporates the time-delay neural network model gives a recognition rate of 75% (69/92) with a false positive rate of 1/547 bases. The present work can be regarded as one of the first intensive studies that applies novel gene regulation technologies to the identification of the complex gene regulation sites in the genome of Drosophila melanogaster. PMID- 11765853 TI - Generating protein three-dimensional fold signatures using inductive logic programming. AB - Inductive logic programming (ILP) has been applied to automatically discover protein fold signatures. This paper investigates the use of topological information to circumvent problems encountered during previous experiments, namely (1) matching of non-structurally related secondary structures and (2) scaling problems. Cross-validation tests were carried out for 20 folds. The overall estimated accuracy is 73.37+/-0.35%. The new representation allows us to process the complete set of examples, while previously it was necessary to sample the negative examples. Topological information is used in approximately 90% of the rules presented here. Information about the topology of a sheet is present in 63% of the rules. This set of rules presents characteristics of the overall architecture of the fold. In contrast, 26% of the rules contain topological information which is limited to the packing of a restricted number of secondary structures, as such, the later set resembles those found in our previous studies. PMID- 11765854 TI - Applications of neural network prediction of conformational states for small peptides from spectra and of fold classes. AB - Electronic structures of small peptides were calculated 'ab initio' with the help of Density Functional Theory (DFT) and molecular dynamics that rendered a set of conformational states of the peptides. For the structures of these states it was possible to derive atomic polar tensors that allowed us to construct vibrational spectra for each of the conformational states with low energy. From the spectra, neural networks could be trained to distinguish between the various states and thus be able to generate a larger set of relevant structures and their relation to secondary structures of the peptides. The calculations were done both with solvent atoms (up to ten water molecules) and without, and hence the neural networks could be used to monitor the influence of the solvent on hydrogen bond formation. The calculations at this stage only involved very short peptide fragments of a few alanine amino acids but already at this stage they could be compared with reasonable agreements to experiments. The neural networks are shown to be good in distinguishing the different conformers of the small alanine peptides, especially when in the gas phase. Also the task of predicting protein fold-classes, defined from line-geometry, seems promising. PMID- 11765855 TI - AI-based algorithms for protein surface comparisons. AB - Many current methods for protein analysis depend on the detection of similarity in either the primary sequence, or the overall tertiary structure (the Calpha atoms of the protein backbone). These common sequences or structures may imply similar functional characteristics or active properties. Active sites and ligand binding sites usually occur on or near the surface of the protein; so similarly shaped surface regions could imply similar functions. We investigate various methods for describing the shape properties of protein surfaces and for comparing them. Our current work uses algorithms from computer vision to describe the protein surfaces, and methods from graph theory to compare the surface regions. Early results indicate that we can successfully match a family of related ligand binding sites, and find their similarly shaped surface regions. This method of surface analysis could be extended to help identify unknown surface regions for possible ligand binding or active sites. PMID- 11765856 TI - Modelling protein side-chain conformations using constraint logic programming. AB - Side-chain placement is an important sub-task in protein modelling. Selecting conformations for side-chains is a difficult problem because of the large search space to be explored. This problem can be addressed using constraint logic programming (CLP), which is an artificial intelligence technique developed to solve large combinatorial search problems. The side-chain placement problem can be expressed as a CLP program in which rotamer conformations are used as values for finite domain variables, and bad steric contacts involving rotamers are represented as constraints. This paper introduces the concept of null rotamers, and shows how these can be used in implementing a novel iterative approach. We present results that compare the accuracy of models constructed using different rotamer libraries and different domain variable enumeration heuristics. The results obtained using this CLP-based approach compare favourably with those obtained by other methods. PMID- 11765857 TI - Progressive dementia: personal and relational impact on caregiving wives. AB - The purpose of this exploratory study was to examine the perceptions of 115 female spouse caregivers of early to moderate stage dementia patients. Based on patients' cognitive status, cross-sectional comparisons of two groups of caregiving wives were conducted. No group differences were found in measures of caregiver burden, depression, or personal gain. However, wives of patients with greater cognitive impairment experienced lower levels of mastery and more relational deprivation when compared to wives of patients with higher mental status. Supportive approaches might be directed toward helping early dementia caregivers restructure their understanding of, and participation in, their marital relationships in anticipation of changes ahead. Interventions aimed at enhancing a caregiver's sense of personal mastery may help reduce the negative effects of dementia on caregivers' well-being. PMID- 11765858 TI - Correlates of personal concerns about developing Alzheimer's disease among middle aged persons. AB - We examine correlates of personal concerns about developing Alzheimer's disease (AD) among (1) adult children, 40 to 60 years of age, who have a living parent with a diagnosis of probable AD (N = 108), and (2) a matched comparison group of persons with no parental history of AD (N = 150). Using stepwise regression, predictors measuring subjective perceptions of memory functioning, overall family history of AD, knowledge of AD, and sociodemographic characteristics were entered into models for the total sample and each of the subsamples. The results indicate that worries about memory functioning play a consistent role in personal concerns about developing AD across both groups, but that additional pathways to personal concerns differ among individuals having and not having a parent with AD. PMID- 11765859 TI - Antecedents, descriptions and consequences of wandering in cognitively-impaired adults and the Safe Return (SR) program. AB - Unattended wandering is a major problem in cognitively impaired (CI) individuals and can result in those individuals becoming lost in the community. The purpose of this study was to identify important characteristics of unattended wandering and important prevention strategies. Data were compiledfrom registration files and missing and discovery reports collected through the Safe Return (SR) program. These data were analyzed to determine where individuals were found, who found them, from what setting they left, what mode of transportation they used, and what circumstances surrounded the unattended wandering. The study highlights the unpredictable and varied nature of unattended wandering. Recommendations are provided for communities to develop strategies to minimize unattended wandering and to determine effective methods of locating CI individuals when they become lost. PMID- 11765860 TI - Depression among Alzheimer's caregivers: identifying risk factors. AB - PURPOSE: The purpose of this study was to reveal risk factors contributing to the development of depression among caregivers of Alzheimer's disease patients. METHODS: In a cross-sectional study, all caregivers of consecutive Alzheimer's disease patients were asked to participate in the study. Patient and caregiver depression was evaluated by using the Yesavage Geriatric Depression Scale (GDS). Information regarding patients' functional status, driving status, and type of behavioral abnormalities was obtained from caregivers. Patients' functional status was evaluated by using the Katz Activity of Daily Living (ADL) scale. The Folstein Mini-Mental Status Examination (MMSE) was used to evaluate cognition. Risk factors for Alzheimer's caregiver depression were assessed by means of logistic regression analysis. RESULTS: A total of 92 patients and caregivers were evaluated. Fifteen were excluded due to incomplete data. A total of 77 pairs were included in this analysis. The age of caregivers ranged from 28 to 88 years. Mean (standard deviation [SD]) age was 63.1 (SD = 16.3) years old. Husbands and wives (caregivers) accounted for 49.4 percent; daughters or sons (or daughters- or sons in-law) accounted for 42.9 percent. There were 29 caregivers (38 percent) found to be depressed. By using multivariate analysis, the following factors have been identified as risk factors for depression in Alzheimer 's caregivers: depression in the dementia patient; ADL functional scores of 12 or greater; and the presence of hallucinations. CONCLUSION: Three risk factors were found to have a strong association with Alzheimer's caregiver depression. Early recognition of such risk factors may help to identify Alzheimer's caregivers with depression. PMID- 11765861 TI - A training workshop on late-stage dementia care for family caregivers. AB - Training workshops have been considered a useful intervention in helping family caregivers of people with dementia to cope with the stress of caregiving. However, there are no reports in the literature with regard to training and support of families specifically looking after individuals who are in the late stage of dementia. This paper reports the experience and evaluation of a training workshop aimed at preparing family caregivers for late-stage dementia care. Eighty-eight percent of the participants completed the client satisfaction questionnaire. The results from the questionnaire gave a very positive response, showing 90.9 percent of respondents were satisfied with the workshop, and 77.3 percent of respondents indicated that their caregiving needs were met. Eleven participants who attended this workshop joined a focus group feedback session. The Kruskal-Wallis test found no significant differences between the overall profile of the participants and that of the focus group in terms of age, gender, educational background, whether they were primary caregivers, for whom they cared (e.g., parents or spouse), or whether the care recipient stayed at home or in a nursing home. Findings from the focus group session provide a somewhat different picture from that of the questionnaire. Three focus group participants provided more critical comments of the workshop. Although the majority of the focus group agreed that the workshop had been useful, they disagreed on whether it is necessary to discuss psychosocial issues in this workshop. Findings from the focus group have enabled the project team to reflect on their design and operation of the workshop and provided valuable insight for future development as well as for further study. PMID- 11765862 TI - Effects of educational attainment on the clinical expression of Alzheimer's disease: results from a research registry. AB - The "reserve" hypothesis suggests that education should affect the clinical expression of Alzheimer's disease (AD), but results from studies examining this idea are not consistent. In a single study, we evaluated the effects of educational attainment on three aspects of the clinical expression of AD: age at symptom onset, rate of cognitive decline, and survival. Subjects were 258 persons with mild- or moderate-stage Alzheimer's, drawn from our AD Research Registry. With statistical adjustment for confounding variables present in a clinic-based design, we found that higher educational attainment was associated with slightly earlier reports of symptom onset and a slower rate of cognitive decline on the Mini-Mental State Exam (MMSE). Education did not affect time of survival until death. We conclude that, for subjects in our sample, education had modest effects on aspects of the clinical expression of AD. These effects were not fully consistent with predictions derived from the "reserve" hypothesis. PMID- 11765863 TI - Keeping the beat: use of rhythmic music during exercise activities for the elderly with dementia. AB - Involving people with dementia in group exercise activities often presents a challenge. The effects of a recorded instrumental musical accompaniment was evaluated on participation in a series of 14 exercise activities with a group of nursing home residents with dementia. All exercise sessions, specifically designed by physical therapists for older adults, were lead by an activity aide and consisted of a series of seated exercises. Direct observations of resident behavior were conducted over a 25-week period in a reversal experimental design. Results showed increased levels of participation during the experimental condition observations where rhythmic music accompanied the exercise activities. The music intervention was most successful on those generally most willing to participate in social activities. PMID- 11765864 TI - Oral and maxillofacial pathology--its future in doubt? PMID- 11765865 TI - Some potential outcomes of the new dental curriculum developed by the Faculty of Dentistry, Dalhousie University, Canada, in the early 1990s. PMID- 11765866 TI - Impact of undergraduate medical training on housestaff problem-solving performance: implications for problem-based curricula. AB - This article reports a study comparing the problem-solving performance of housestaff with undergraduate medical training in either conventional or problem based schools. After reading two clinical cases, residents were required to write differential diagnoses and pathophysiological explanations. Biomedical and clinical knowledge used and reasoning strategies were identified. The results suggest that housestaff performance is influenced by the nature of instruction. Housestaff trained in a conventional curriculum (CC) focused on patient information, separated biomedical from clinical knowledge, and used data-driven strategies. Housestaff from problem-based learning curricula (PBLC) organized their knowledge around generated inferences, integrated biomedical and clinical knowledge, and used hypothesis-driven strategies. Data-driven reasoning appears to be impeded in PBLC, suggesting that PBLC students have difficulties in acquiring problem schemata. Previous investigations also found this pattern to be true for medical students trained in two different curriculum formats. Although all housestaff generated equal numbers of diagnostic hypotheses during the reasoning process, housestaff from the conventional curriculum generated a greater number of accurate hypotheses than residents in PBLC. These results are discussed in relation to assumptions in health professional curricula about the adequacy of hypothetico-deductive methods of reasoning as teaching mechanisms and the need for clinical and biomedical knowledge integration. PMID- 11765867 TI - Problem-based learning and the dental school library. AB - A major curriculum revision involving the utilization of problem-based learning was implemented at Indiana University School of Dentistry in the summer of 1997. Two of the main goals of this new student-centered curriculum were to promote critical thinking skills and to encourage a desire for lifelong learning, both of which were anticipated to increase student use of the library. This study examined circulation at the library for three years immediately prior to, and for three years immediately following, the curricular change. Results show that library circulation has increased significantly since the pedagogical change. This suggests that students in the new curriculum place more emphasis on the library as a learning resource than did their traditional curriculum counterparts. PMID- 11765868 TI - Use of simulation technology in dental education. AB - Simulation is becoming very beneficial in the area of health care education. Dentistry has used various types of simulation in preclinical education for some time. This article discusses the impact of the current simulation laboratories on dental education and reviews advanced technology simulation that has recently become available or is in the developmental stage. The abilities of advanced technology simulation, its advantages and disadvantages, and its potential to affect dental education are addressed. PMID- 11765869 TI - Purposeful assessment techniques (PAT) applied to an OSCE-based measurement of competencies in a pediatric dentistry curriculum. AB - Careful measurements of knowledge, attitude, and psychomotor and communication skills are necessary components of testing in a competency-based approach to education in dentistry. In an effort to address these requirements, Baylor College of Dentistry (BCD), Dallas, Texas, has applied Purposeful Assessment Techniques (PAT) to the Objective Structured Clinical Examination (OSCE) currently in use. PAT are those techniques that allow one to work toward development of linear measurement scales that are "person-free" and "item-free." Person-free measurement means that useful data are produced regardless of the group being measured and item-free measurement means that it does not matter which mix of items is completed over the course of an assessment. The Rasch probabilistic model and a guiding definition of Objective Measurement were used in an effort to implement PAT for the BCD OSCE. A Rasch analysis of a BCD administered OSCE produced an item map that demonstrated the range of difficulty of items by student performance. This item map can be used to determine which items can be repeated on subsequent tests to allow for linear measurement of students' progression through the curriculum. The movement toward PAT described in this paper demonstrates how careful and evolving measurement in dental education can be of great benefit to faculty, staff, students, and the public. PMID- 11765870 TI - University of Kentucky community-based field experience: program description. AB - Community-based field experiences (CBFE) provide students with exemplary experiential learning opportunities. The purposes of this paper are to describe the University of Kentucky College of Dentistry (UKCD) CBFE and report the results of a two-year, self-report survey that assessed the primary course goal, students' perceptions of change in knowledge and skills related to nineteen areas of patient care (n = 90, 100% return rate), and their overall rating of the program. Knowledge and skill data were analyzed using the non-parametric binomial test for comparing proportions. A significant (.05 level) majority of students reported increases in knowledge in all areas to which they were exposed. Descriptive frequencies summarizing the results of the total CBFE experience indicate that the majority of students felt it was a positive experience. The CBFE continues to be a meaningful element in the UKCD curriculum as it provides students with a relevant, authentic educational experience. PMID- 11765871 TI - Preliminary evidence for a general competency hypothesis. AB - Although predoctoral dental education is generally taught and evaluated by disciplines, there is no evidence bearing on whether the competencies necessary to begin independent practice are learned and practiced as a general set of skills, understanding, and values or as groups of discipline-specific skills, understanding, and values, which together constitute graduation competency. There is some support in the literature for each view In this preliminary investigation, 64,000 faculty ratings of student clinical competency were analyzed in a Year x Quarter x Discipline x Model design. The dependent variable was predictive validity of graduation quarter competency ratings using R-values from four prediction models. Results of a multiple repeated measures ANOVA show that models based on technical skills other than the one being predicted, clinical judgment and patient management, and the combination of these two models all predict graduation competency in each of four disciplines better than do ratings in the disciplines being predicted. As the time gap between predictive and predicted competence decreases, predictions become more accurate, but an asymptote is reached by the middle of the final clinical year. By using general models to evaluate students rather than discipline-specific ones, students needing intervention and remediation and those who could benefit from enrichment experiences can be identified as accurately at the beginning of their clinical careers as they can near the graduation deadline. This study provides preliminary support for a general competency hypothesis and suggests that research is necessary to better understand how students and dentists learn and practice rather than how they are taught. PMID- 11765872 TI - Creating a school without walls and building a learning organization: a case study. AB - Abstract: This article describes the genesis of a "school without walls" philosophy and the implementation of learning organization principles at Boston University School of Dental Medicine (BUSDM). In Peter Senge's five-discipline approach to organizational learning, a learning organization is defined as "an organization that is continually expanding its capacity to create its future." It is an organization that changes and innovates based on continuous learning, which in BUSDM's case constituted learning from industry trends, patients, students, staff, faculty, and other key stakeholders. Most important, such organizations successfully translate that learning into effective action. It is this capacity to innovate and create change that is critical to competitive advantage and success in a changing environment. This case study of organizational change provides a discussion of the conceptual framework guiding the design and implementation of the learning organization and the chronology of transformation that occurred in three phases over a period of twenty years. We also describe the lessons we learned and the lessons that are still emerging. PMID- 11765873 TI - Patient satisfaction with the comprehensive care model of dental care delivery. AB - In the summer of 1997, the College of Dentistry, The Ohio State University, changed its predoctoral clinics from the traditional model to the comprehensive care (CC) model. Although the CC model is considered the better model for delivery of care, from the patient perspective it has not been previously evaluated. The purpose of this study was to compare the two dental care delivery systems--the traditional model and the CC model--using patient satisfaction. The Dental Satisfaction Questionnaire (DSQ) developed by the Rand Corporation was used to assess patient satisfaction. The questionnaire consists of nineteen items, measuring overall satisfaction and subscales of access, pain management, and quality. The questionnaire was self-administered to active and recall patients in the summers of 1997 and 1998 to evaluate satisfaction with care in the traditional and CC models respectively. The completed DSQ was returned by 119 respondents in 1997 and 116 respondents in 1998. There were no significant differences in age. gender, and self-rated general and oral health of patients using the two delivery systems. No statistically significant differences were seen in the overall Dental Satisfaction Index and the sub-scales of access, pain management, and quality of care. Statistically significant differences were observed on only two of the nineteen individual items. We conclude that there was no difference in satisfaction levels of our patients between the two dental care delivery models. PMID- 11765874 TI - U.S. and Canadian dental school involvement in extramural programming. AB - This project was undertaken from July 1999 to August 2000 to identify the status of extramural programming (that is, a program that has undergraduate dental students providing any aspect of dental care to individuals in settings outside the main clinical facility of the school) in North American dental schools. A survey instrument was mailed to all United States and Canadian dental schools concerning student involvement in extramural programming. The response rate was 79.7 percent. Of the schools responding, 3.9 percent did not offer extramural programming. The type of extramural sites, the percentage of schools offering each type of site, and the mean number of weeks students are at each site were as follows: hospital clinics--71 percent, 2.5 weeks; public health clinics--65 percent, 6 weeks; schools and day care centers--49, 1.7 weeks; private dental offices--37 percent, 2 weeks; and "other"--29 percent, 2.5 weeks. The average number of weeks spent at extramural site(s) per class was: freshman 1.9 weeks (SD=4.3); sophomores 2.3 weeks (SD=4.2); juniors 2.6 weeks (SD=1.9); and seniors 5.3 weeks (SD=6.7). Of total student time in extramural programming, 43.3 percent was spent delivering basic clinical services, 24.4 percent comprehensive clinical services, 11.8 percent health education, 11.8 percent preventive dentistry, and 8.7 percent community activities. From the data collected it is apparent that the majority of North American dental schools are providing a variety of extramural experiences for their dental students. It was found that student involvement in extramural programming increases gradually from the freshman to the senior year. PMID- 11765875 TI - Disinfection/sterilization of extracted teeth for dental student use. AB - Extracted human teeth are used in many preclinical courses. While there has been no report of disease transmission with extracted teeth, sterilization of teeth used in the teaching laboratory should be a concern. The purpose of this study was to determine the effectiveness of different sterilization/disinfection methods of extracted human teeth using Bacillus stearothermophilus, a bacteria resistant to heat and frequently used to test sterilizers. In this study, 110 extracted molars with no carious lesions were collected and stored in buffered saline. An endodontic occlusal access preparation was cut into the pulp chamber of each tooth. Pulp tissue in the chamber was removed with a broach. Approximately 1 x 10(5) B. stearothermophilus endospores in culture medium were injected into the pulp chamber, sealed with Cavit G, and then placed in sterile saline for twelve hours. Ten teeth were placed into each of eleven groups. Seven groups were immersed for one week in one of the following solutions: a) sterile saline (control group), b) 5.25% NaOCl, c) 2.6% NaOCl, d) 1% NaOCl, e) 10% buffered formalin, f) 2% gluteraldehyde, g) 0.28% quaternary ammonium. Four additional groups were treated by h) 10% formalin for two days, i) 10% formalin for four days, j) autoclaving at 240 degrees F and 20 psi for twenty minutes, and k) autoclaving at 240 degrees F and twenty psi for forty minutes. Each tooth was then aseptically split and placed in an individual test tube with growth medium. Samples were examined for evidence of growth (turbidity) at forty-eight hours. Only autoclaving for forty minutes at 240 degrees F and 20 psi or soaking in 10 percent formalin for one week were 100 percent effective in preventing growth. A chi-square analysis of the data indicates these two methods were significantly better than all other methods (p<0.001). PMID- 11765876 TI - Angiogenesis in oral cancer. AB - Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that develops after years of chronic exposure to alcohol and tobacco products. Exposure to these agents results in alterations of genes that are important in the regulation of various cellular functions. This loss of regulation allows the tumor cells to survive and grow in an unchecked manner by allowing the cells to perform functions that contribute to the growth of the tumor. Some of these important changes include the acquisition of immortality and the ability to invade tissue and/or metastasize to other sights, as well as acquiring the ability to induce angiogenesis. Angiogenesis, the growth of new blood vessels from pre-existing ones, is a complex phenomenon that is absolutely required for the continued growth and survival of solid neoplasms. Without new blood vessels to provide nutrients and remove waste, tumors would be unable to grow larger than 2-3 mm in diameter. Therefore, one could envision its potential role in both the treatment and prevention of malignancies such as HNSCC. The concept of chemoprevention is extremely important in HNSCC since patients often develop multiple independent lesions throughout the mucosa of the upper aerodigestive tract. Therefore, the comprehensive treatment of this disease must address not only the initial primary neoplasm, but also prevent the progression of the premalignant lesions lurking throughout the rest of the mucosal surfaces. This review will outline the basic changes that occur in tumor cells that result in the switch to angiogenic phenotype. In addition, it will discuss the present status of using antiangiogenic agents in the treatment of cancer. Finally, this paper will present a rationale for the use of multiple antiangiogenic agents as a means of developing new chemotherapeutic and chemopreventive protocols that may result in reduced patient toxicity while maintaining similar clinical efficacies. PMID- 11765877 TI - Dental school vacant budgeted faculty positions: academic year 2000 - 2001. AB - The 1999 Report of the AADS President's Task Force on the Future of Dental School Faculty (1) drew attention to the situation dental schools are experiencing in attracting and retaining faculty. A year 2000 ADEA Association Report on faculty shortages indicated the number of vacant budgeted positions was approaching 400 (2). The year 2000 - 2001 ADEA survey of vacant budgeted positions indicates a further four percent increase in vacant budgeted positions. Over 73 percent of the vacancies were in the clinical sciences. Of identified full time faculty separations in the 2000-2001 ADEA Survey of Dental Educators (3), almost 34 percent were due to retirements; 33 percent were faculty moves to other schools; and a little over 18 percent were moves to enter private practice. Almost three percent of identified faculty separations were from deaths. It is anticipated that, with a further "graying" of an already aged dental school faculty, retirements will further exacerbate the problem of faculty vacancies and the ability to attract and retain new faculty. There is needed urgency in implementing strategies and recommendations provided in the 1999 President's Report and the 2000 Association Report. PMID- 11765878 TI - How much do rural Hispanics know about the adverse health risks of smoking? AB - The object of this study was to measure knowledge in a rural Hispanic community about the adverse health effects of smoking and to compare knowledge between current smokers and nonsmokers. A survey was administered to waiting room patients (n =137) over 16 years old at three predominantly Hispanic rural community health centers in the central San Joaquin Valley of California. Proportions of respondents who believed that smoking caused a specific consequence were calculated and compared between smokers and nonsmokers by chi square tests. Likelihood of attributing negative health consequences to smoking was determined and compared between smokers and nonsmokers. A majority of all participants (smokers and nonsmokers) knew that smoking causes lung cancer (93 percent) and emphysema (91 percent). Many fewer participants knew that smoking contributes to problems such as osteoporosis (39 percent) or sexual dysfunction (33 percent). Current smokers were less likely than nonsmokers (P=0.01) to say that smoking causes any adverse health outcome, including those not known to be related to smoking. Although this is a culturally, ethnically and geographically unique group, knowledge of smoking risks among smoking and nonsmoking rural Hispanics is similar to that found in the general population. When compared with nonsmokers, current smokers underestimate the risk that smoking poses to health. PMID- 11765880 TI - The effects of payback and loan repayment programs on medical student career plans. AB - Many states have considered implementing payback programs on state-subsidized medical education to increase the rate of graduates returning to those states to practice. An alternative is for states to offer and expand loan repayment programs to entice medical school graduates from rural states to return to their home states. The goal of this study is to determine and contrast the impact these two types of programs might have on medical school choice and students' intentions to return to their home states. Two hundred twenty-nine medical students were surveyed (response rate 80 percent). The questionnaire collected background information on the students and addressed the possible impact of payback and loan repayment policy proposals on student plans. Forty-seven percent of students reported that they would attend a different medical school if a required payback program were in place. Students who were more competitive at the time of admission to medical school were significantly more likely to say they would attend another medical school than were less competitive students. In contrast, 48 percent of students reported that they would be more likely to return to their home states if expanded loan repayment programs were available for service in areas of need. The findings suggest that payback programs may dissuade more competitive students from entering medical schools with such requirements, compromising the pool of students most likely to return to rural areas. Conversely, medical students appear willing to consider loan repayment programs upon completion of their training. PMID- 11765879 TI - Developmental screenings in rural settings: a comparison of the child development review and the Denver II Developmental Screening Test. AB - Screening results for the Child Development Review (CDR) and the Denver II Developmental Screening Test (Denver II) were compared in two locations: the Cheyenne River Reservation in South Dakota and Sioux Falls, S.D. Seventy-three white, Native American and other minority children, half originating from the reservation and half from Sioux Falls, were randomly assigned to take one developmental screening test. A chi-square analysis indicated a significant difference in results across tests. Specifically, more CDR than Denver II subjects passed the screening and more Denver II than CDR subjects failed the screening. This pattern held for subjects living on, but not off, the reservation. Thus, for Native American, white and other minority children living on the Cheyenne River Reservation, the CDR may be undersensitive and/or the Denver II oversensitive to suspect presentations. Medical practitioners are advised to use these instruments with caution in rural settings. PMID- 11765881 TI - The contributions of business and civil society sectors to rural capacity to solve local health issues. AB - The new health movement, which has emerged over the last decade, focuses decision making for program designs, interventions and health policies at the local level. This movement assumes that rural communities have the capacity to deal with local health issues. Local problem-solving capacity is based in local leadership patterns, relationships among different community sectors and the ability to select critical but feasible goals. In this research, 159 community leaders in 16 rural counties were interviewed regarding local health priorities, organizational interactions, and leadership roles in county health issues. Analysis of variance was used to identify differences among community sectors. The business and industry sector was found to interact with other organizations around health issues significantly less than all other sectors. Further, 69 percent of the business and industry sector compared with 32 percent of all other sectors thought that the business sector was a source of local leadership. The civil society sector, when compared with all other sectors, was significantly more likely to give priority to health services such as primary, specialty and auxiliary care goals. These findings suggest that rural communities need to find ways to more actively involve the business and industry sector in local health problem solving. In addition, the civil society sector brings to community problem solving a set of priorities that are often different from other sectors of the community. PMID- 11765882 TI - The Kentucky Homeplace Project: family health care advisers in underserved rural communities. AB - The Kentucky Homeplace Project (KHP) is a state-legislated program designed to address well-documented deficits in the health status of and health resources available to many of Kentucky's rural residents. Since its inception in 1994, the KHP has served approximately 80,000 clients, primarily through home visits by trained, locally residing paraprofessionals known as family health care advisers. These family health care advisers employ culturally appropriate strategies to meet immediate needs as well as to foster long-term client empowerment and the adoption of health prevention strategies. This descriptive examination of KHP provides information regarding (a) the advantages of the program, with specific attention to its orientation toward provision of culturally appropriate health services; (b) the disadvantages of KHP, including competing budgetary priorities and its vulnerability to local economic and political trends; and (c) the potential application of similar programs for other rural, difficult-to-reach populations. PMID- 11765883 TI - The effect of Medicaid managed care on rural public health departments. AB - Medicaid managed care programs are now operating in more than half of all rural counties in the United States. This study examines how rural health departments that have historically provided clinical services have responded to and been affected by the implementation of Medicaid managed care. To the extent that rural health departments have changed, the effect of this change on the health department and the rural populations that these providers serve is assessed. Site visits were made to four rural public health departments in each of five study states, for a total of 20 case studies. At each site, in-person interviews of county public health department directors were conducted using semistructured interview protocols. In recent years, the majority of health departments decreased or discontinued provision of well-child services, causing many to lose Medicaid revenue. None of the health departments appeared to be in danger of closing, but most lost income security. Medicaid managed care appeared to have increased the number of children with medical homes in the private sector, but adequacy and continuity of care remains an issue. Privatizing Medicaid managed care has not decreased fragmentation, as public health functions such as tracking and screening represent an important facet of comprehensive health services for poor rural populations. PMID- 11765884 TI - Consumer perspectives on Medicaid managed care: a comparison between rural and urban enrollees in one selected health plan. AB - This report presents the findings from a telephone survey of 313 respondents who have family members enrolled in Medicaid managed care in a multicounty region that encompasses both rural and urban counties in Wisconsin. Some demographic differences were noted between the rural and urban families that might affect their impressions of the health care system, their needs for services and their abilities to use those services appropriately. Families in the urban counties had poorer access to health care, as they were more likely to report at least one child not being assigned to a primary care provider. Inadequate preventive health behaviors were found among both rural and urban families, as evidenced by children being overdue for immunizations or health checkups. Yet respondents reported being happy with the care they received. Rural families in particular seemed to fare well in this managed care system. PMID- 11765885 TI - Rural hospitals and the adoption of managed care strategies. AB - This research examined the performance of rural hospitals engaged in different levels of managed care activities and identified factors related to performance and competition that affected rural hospitals' likelihood of pursuing managed care as a strategy. The sample studied consisted of 139 rural hospitals in Iowa and Nebraska. Results showed that a relatively high percentage of hospitals were engaged in managed care activities, mainly through contractual arrangements. The study found that high competition in the marketplace increased the likelihood of hospitals pursuing managed care strategies, while high demand markets had a negative association with the likelihood of pursuing a managed care strategy. No significant relationship was detected between poor performance and pursuing a managed care strategy. PMID- 11765886 TI - Using telemedicine to avoid transfer of rural emergency department patients. AB - Access to emergency treatment in rural areas can often mean the difference between life and death. Telemedicine technologies have the potential of providing earlier diagnosis and intervention, of saving lives and of avoiding unnecessary transfers from rural hospital emergency departments to urban hospitals. This study examined the hypothetical impact of telemedicine services on patients served by the emergency departments of two rural Missouri hospitals and the potential financial impact on the affected hospitals. Of the 246 patients transferred to the hub hospital from the two facilities during 1996, 161 medical records (65.4 percent) were analyzed. Using a conservative approach, only 12 of these cases were identified as potentially avoidable transfers with the use of telemedicine. Of these 12, 5 were admitted to the hub hospital after transfer. In addition to this conservative estimate of avoidable transfers based on current availability of resources in the rural hospitals, two more aggressive scenarios were developed, based on an assumption of increased service availability in the rural hospitals. Economic multipliers were used to estimate the financial impacts on communities in each scenario. This evaluation study demonstrates the potential value of telemedicine use in rural emergency departments to patients, rural hospitals and rural communities. PMID- 11765887 TI - Functional disability at nursing home admission: a comparison of urban and rural admission cohorts. AB - This study's objective was to examine the relationships between rural residence and availability of nursing home and home health care to functional disability at the time of nursing home admission. Secondary data were obtained from the Minimum Data Set (MDS) 2.0 for Nebraska for 3,443 rural and 1,296 urban older people admitted to nursing facilities. Data from the MDS were merged with county-level data on home health agencies and nursing homes in Nebraska. The relationship of rurality of nursing home residents' prior residence and availability of nursing home and home health care to functional status at admission, controlling for demographic and health characteristics of older people, was estimated using multiple linear regression with robust variance estimates. After taking account of demographic and health status characteristics, rural residence and availability of home health and nursing home care had nonsignificant effects on functional status at admission. The findings indicate that functional disability at admission is associated with specific diseases and medical conditions, cognitive status, gender, living arrangements and marital arrangements. Rural older people are not at higher risk of admission at lower levels of functional disability compared to their urban counterparts. PMID- 11765888 TI - Productive efficiency of rural health clinics: the Midwest experience. AB - This article identifies the characteristics of efficient and inefficient rural clinics in the Midwest, using 1994 Medicare cost reports. Rural health clinics are compared on the basis of productive efficiency by estimating a nonparametric frontier. Six inputs and five output categories were employed to estimate an efficient frontier. The results show that an efficient clinic, on average, employs approximately 1.5 more physicians than an inefficient clinic and incurs capital expenses more than twice those of the inefficient clinic. Future rural clinics are expected to be larger, employing more capital and labor to take advantage of scale economies. However, given the steady (or decreasing) population of rural communities, the expansion of relatively small rural clinics could involve forming rural health care systems and/or networks in close proximity to create synergies from scale economies, staff recruitment, easier access to capital, shared information systems, improved mobility of physicians among several clinics and savings from management costs. PMID- 11765889 TI - Characteristics of and issues faced by rural female family physicians. AB - The purpose of this study was to identify characteristics of and issues faced by female family physicians practicing in rural areas. A 37-item survey was designed to obtain demographic information about the background, community and practice of rural female physicians. An open-ended question regarding the issues and problems faced by female physicians in rural communities was included. Study subjects were identified from the membership of the American Academy of Family Physicians (AAFP). The questionnaire was mailed to all 850 active female AAFP members practicing in communities with less than 50,000 inhabitants during the winter of 1999. Completed and usable surveys were received from 587 (69.9 percent). The average age of respondents was 45. The majority were married (81.1 percent) and had children (80.1 percent). Half of the women had grown up in communities of 25,000 or less population. Twenty-seven percent of the respondents had no rural exposure in medical school; 39 percent had no rural exposure in residency; and 16 percent had no rural exposure in medical school or residency. The majority of respondents (62 percent) practiced in communities of less than 10,000. A large majority (70 percent) of these women planned to stay in the community for 10 years or more, with 58.6 percent responding that they plan to stay indefinitely. Assumptions regarding rural physicians, especially women, must be updated to accurately assist communities in recruiting rural physicians and to assist medical schools and residencies in adequately preparing graduates for rural practice. PMID- 11765890 TI - Predicting level of mental health care among children served in a delivery system in a rural state. AB - The purpose of this study was to establish benchmark data to assist in identifying factors associated with mental health service needs and level of care for children living in a rural state. Clinical and psycho-social needs and strengths were assessed using retrospective chart review for all children and adolescents (n=150) with symptoms or a diagnosis of reactive attachment disorder who presented to a comprehensive treatment facility between January 1997 and December 1999. Logistic regression was used to predict factors associated with inpatient admission (n=15) vs. community-based care (n=135). Significant individual contributors to the prediction of inpatient care were more limited clinical/psycho-social strengths, history of inpatient use and history of sexual abuse. Although 80 percent of children admitted to inpatient care had a history of hospitalization, two-thirds had no history of receiving community-based services and presented to current treatment with a two-year or longer history of symptoms. Approximately two-thirds of children admitted to inpatient care had a history of sexual abuse; however, one-third of these children had no history of mental health service use and presented to current treatment with a two-year or longer history of symptoms. Findings raise concerns about current efforts in public health education, community awareness and health prevention and early intervention programs for children with mental/behavioral health challenges and children and families at risk for abuse and/or neglect living in rural areas. PMID- 11765891 TI - Impact of a rural domestic violence prevention campaign. AB - Domestic violence is a prevalent health problem that in rural areas is further complicated by limited services, social isolation and the lack of privacy. Little is known about the impact of public health education on awareness, attitudes and behavior of the general public regarding domestic violence. This study sought to measure change in societal attitudes and behavioral intention in response to a seven-month public health education campaign targeting domestic violence in a rural county. From October 1998 to April 1999, the campaign used radio advertisements, posters, mailings to libraries and clergy, printed media articles, printed advertisements and health facility modifications. A random digit-dialing telephone survey was used to evaluate attitudinal and behavioral changes in the intervention and comparison counties before and after the campaign. The response rates for the pre- (n =378) and postcampaign (n=633) surveys were 73 percent and 65 percent, respectively. Statistically significant increases in slogan and advertising recognition occurred in the intervention county (P=0.03), particularly among men recalling the campaign slogan (P=0.006). In a vignette regarding actions to be taken if the neighbor next door was abusing a partner, significant increases occurred in the intervention county in the percentage of respondents who thought that most people would talk to the victim (P=0.04), consult with friends (P=0.002) or talk to a doctor (P=0.004). Domestic violence agency hotline calls in the intervention county doubled following the campaign. Local public health education campaigns in a rural setting may be a valuable adjunct to national efforts, especially in reaching men. PMID- 11765892 TI - Perceptions of important retention and recruitment factors by therapists in northwestern Ontario. AB - Recruitment and retention of health professionals in rural and remote communities are well-known challenges. Although the literature states that lifestyle factors and being from a rural background influence recruitment and retention, much of the research is dated and of limited relevance to rehabilitation professionals. This study reports on a survey of physical therapists (PTs) and occupational therapists (OTs) in northwestern Ontario. Seventy-four percent of the OTs and PTs from this geographically isolated region of Canada responded to a mail survey examining factors that influenced their job recruitment and retention decisions. Availability of leisure and recreation activities, proximity of family of origin, need for OTs and PTs and influence of spouse or partner frequently contributed to recruitment decisions and were also important in retention decisions. Although professional autonomy was an important source of job satisfaction for the respondents, almost one-third reported a feeling of professional isolation. Professional development initiatives appeared to influence job satisfaction but were unlikely to influence working life decisions. The findings suggest that recruitment and retention strategies should be multifaceted to reflect the complexity of therapists' decision-making. PMID- 11765893 TI - Collaboration and integration of community-based health and human services in a nonprofit managed care system. AB - This article reports the results of research on a single, urban system of health and human services delivery for clients with serious mental illness. The primary focus was to examine how collaboration and services integration among the more than 40 mostly nonprofit provider agencies were affected by the introduction of managed care. A critical factor in explaining the results was the role of the behavioral health authority in implementing and managing the system. PMID- 11765894 TI - Strategies for more efficient performance through hospital merger. AB - This article compares the operating performance of merged and non-merged local hospitals during the late 1980s and early 1990s, a period not unlike that being experienced in hospitals today. A matched case-control design is employed to create "synthetically" merged hospitals--to represent them as if they had effected a merger--and compares their performance to a group of similar hospitals that did merge. PMID- 11765895 TI - Managing system errors and failures in health care organizations: suggestions for practice and research. AB - The inherent design of health delivery systems predisposes them to errors and gradual rates of improvement. Health care executives and researchers should understand the importance of system errors and the role of leadership in removing perturbations that adversely affect health care organization performance. This article presents insights on strategies for addressing system errors and for reducing the magnitude of the problem. PMID- 11765896 TI - Empirical support for the Baldrige Award framework in U.S. hospitals. AB - Examined are relationships among constructs in the Baldrige Award Health Care Criteria framework to investigate whether quality management systems are related to organizational results and customer satisfaction in hospitals. Measures for the 19 dimensions of the Baldrige Criteria are obtained from 220 U.S. hospitals. This study provides empirical evidence that focusing on the content addressed in the Baldrige Criteria leads hospitals to improvement on some dimensions of performance. PMID- 11765897 TI - Hospital reorganization and restructuring achieved through merger. AB - This article examines hospital reorganization and restructuring activities following merger for two study periods: 1983-1988 and 1989-1996. In both periods, hospitals rated strengthening hospital financial position as the most important reason for merger. There were also similarities in reorganizing actions, especially reductions in service duplication, consolidation of departments and programs, reductions in medical and support FTEs, and reductions in administrative staffing. Hospital mergers during 1989-1996, however, focused increasingly on reducing nursing FTEs and less on converting acquired hospitals to new service lines. PMID- 11765898 TI - Toward a population health delivery system: first steps in performance measurement. AB - In spite of the technological sophistication and clinical excellence of the U.S. health care industry and annual health expenditures in excess of a trillion dollars, the overall health status of the American population is comparatively poor. The BCHS in west central Florida sought to improve the health status of the communities that it serves. Known by the acronym CHAPIR, an information-driven health status decision support system was developed, pilot tested, and is now fully implemented throughout the BCHS. The methodological approach, quantitative indicators, report format components, and management implications of the system are described. PMID- 11765899 TI - Purification of soluble recombinant human FcgammaRII (CD32). AB - The present study describes the methodology used to purify human recombinant low affinity FcgammaRIIa2 produced in E. coli and to evaluate its binding to surface IgG. The recombinant molecule was purified by a two-step chromatographic procedure, including affinity chromatography using IV.3 anti-FcgammaRIIa1/2 immunosorbent, followed by gel filtration chromatography. Using this method, the purified recombinant FcgammaRIIa2 was 99% pure. It exhibited an isoeletric point of 5.2. Binding studies demonstrated a specific binding of the purified recombinant molecule to surface IgG expressed by human B cells. Thus, we have set up a method which allows to purify functional human recombinant FcgammaRIIa2 for further characterization of its biological activities. PMID- 11765900 TI - Purification and partial characterization of an alpha-2,8-sialyltransferase from human erythroleukemia K562 cells. AB - An alpha-2,8-sialyltransferase (ST8), the enzyme involved in the biosynthesis of polysialic acid chains, has been purified and partly characterized from undifferentiated human erythroleukemia K562 cells. Purification, based on a key step of affinity chromatography utilizing immobilized colominic acid, was greater than 1000-fold. The enzyme molecular weight determined by SDS-PAGE was estimated to be about 40 kDa, in good agreement with literature data. For the determination of the main kinetic parameters (Vmax and K(M)), fetuin turned out to be the unique substrate acceptor. In fact, other compounds such as asialofetuin, transferrin, alpha1-acid glycoprotein, and G(M3), routinely used to explore the different ST8 isoforms' activities, did not serve as substrate acceptors. In all cases, contrary to the routinely adopted protocol where a radioactive substrate donor is employed, for our purpose a non-radioactive, fluorescent substrate donor such as cytidine-5'-monophospho-9-(3-fluoresceinylthioureido)-9-deoxy-N-acetyl neuraminic acid (CMP-9-fluoresceinyl-NeuAc) was used. Thus, under our experimental conditions, by using fetuin, data reported in a typical Lineweaver Burk plot gave a Vmax value of about 4 nkatal/mg of protein and a K(M) value around 0.61 mM. Just as with the estimated molecular weight, these kinetic data were also in good agreement with those already reported for the ST8 purified from human neuroblastoma CHP-134 cells. In particular, in both cases, Vmax values were almost similar (4 nkatal/mg of protein for our ST8 purified from K562 cells and 4.35 nkatal/mg of protein for ST8 purified from CHP-134 cells); conversely, the K(M) value we found was about 3.25-fold lower than that found by Stoykova and Glick (0.61 mM vs. 2 mM). Then, although our purification was lower than that obtained by Stoykova and Glick (1080-fold vs. 2910-fold), the enzyme we purified showed a greater apparent affinity. PMID- 11765901 TI - Gel electrophoretic isolation, in the hundred microgram range, of recombinant SDS syntaxin from sea urchin egg cortical vesicles. AB - Recombinant urchin syntaxin [Xa cut], electrophoresed at pH 9.0 (25 degrees C) or 10.2 (0 degrees C) in a discontinuous Tris-chloride-glycinate buffer system in the presence of 0.03% SDS in the catholyte, exhibits a multicomponent pattern in gels of a polyacrylamide concentration of 12% and 3% crosslinking. The position in the pattern of the syntaxin band was identified by reference to electropherograms of a previous study (P. Backlund, pers. comm.). The complexity of the protein composition of the preparation was reduced by selective stacking of proteins with mobilities greater than that of syntaxin. This provides a gel pattern consisting of two bands with mobilities close to that identified as syntaxin, as well as a minor, more slowly migrating, contaminant. The two major components are designated as S1 and S2, the latter being the larger species. In the absence of SDS, the preparation exhibits two pairs of protein components. Three of the proteins are charge isomers, i.e., of equal size, differing only in net charge, assumed to be forms of S1, while the fourth component is larger and is assumed to be S2. Aliquots of the preparation, containing 150 microg of protein were loaded on a cylindrical polyacrylamide gel of 18 mm diameter, and separated S1 and S2 were excised in a position defined by their characteristic values of relative mobility (Rf). Two or three gel slices, corresponding in Rf to S1 or S2, were pooled and loaded onto a Stacking Gel (5% polyacrylamide, 20% cross-linked) of 18 mm diameter, equipped with a collection chamber of 200 microL volume. The protein was electroeluted from the gel slices and concentrated into a stack by electrophoresis. The stack, marked by bromphenolblue, was allowed to migrate into the collection chamber, was collected and analyzed by protein assay and re-electrophoresis. Re-electrophoresis of S1 shows that it consists of at least three components. Recovered S1 constitutes 47% of the preparation, based on protein assay, S2 4%. S1, isolated from SDS-PAGE, exhibits an apparent Mr of 22.7 kDa, S2 one of 34.5 kDa, similar to the value of 32.6 kDa expected from the structure of syntaxin. The absence of S2 from the electroeluate re electrophoresed at 0 degrees C and their molecular weight relationship suggest a proteolytic transformation of S2 to S1. PMID- 11765903 TI - Simplified method for the detection of apo(a) isoforms. AB - Apolipoprotein a, is a high molecular weight glycoproteic component of Lp(a), a molecule associated with coronary arterial disease. Apo(a) exhibits considerable size heterogeneity due to variable repetitions of the carbohydrate-containing structural unit, termed kringle. There are five different kringle forms and 10 different kringle 4 types. Apo(a) polymorphism and molecular weight depend on the number of copies of kringle 4 type 2. In this paper we describe a modified 3.75% and 6% discontinuous polyacrylamide gel system and Western-blot technique that shortness the assay time and improves the identification of apo(a) isoforms with a theoretical error of less than 1 kringle. The assay uses a standard curve prepared with five different recombinant apo(a) molecules, detected up to 50 ng of protein in Lp(a), showed a maximal resolution of 2 kringles and, with the use of third degree polynominal regression analysis, had an error of 0.01275. The inter-assay coefficient of variation was 1.7, 2, and 1.4 for the 14 K, 18 K, and 22 K phenotypes, whereas the intra-assay coefficient of variation was 0.32%, 0.18%, and 0.17%, respectively. It is possible that this modified method will diminish the number of putative null alleles so far detected in various studies, but most of all, we are certain that it can be of use in epidemiological studies due to its ease of use, speed, low cost, and enhanced number of samples that can be tested. PMID- 11765902 TI - Cloning, characterization, and expression of xylanase gene from Bacillus lyticus in Escherichia coli and Bacillus subtilis. AB - A genomic library of Bacillus lyticus was constructed in lambda GEM 11 vector and screened for the xylanase gene using Congo red plate assay. A 16-kb fragment containing the xylanase gene was obtained which was further subcloned using Mbo I partial digestion in an E. coli pUC 19 vector. A 1.3-kb sub-fragment was obtained which coded for a xylanase gene of Mr 23,650 Da. This fragment was sequenced and the homology was checked with known xylanases. The maximum homology was 97%, which was obtained with an endo xylanase gene from Bacillus species at the DNA level, while the translated sequence showed only one amino acid change from alanine to serine at position number 102. Expression was checked in E. coli, using the native promoter, and an extracellular activity of 5.25 U/mL was obtained. Cloning of the gene was done in Bacillus subtilis using a shuttle vector pHB 201, which resulted in increasing the basal level xylanase activity from 14.02 to 22.01 U/mL. PMID- 11765904 TI - Synthesis of novel potential antitumor agents: 2,6-dimethoxyhydroquinone-3 mercapto-acetyl peptide conjugates. AB - This paper reports on an ongoing study of the use of short chain peptides as carriers of a potential anti-tumor agent: 2,6-dimethoxyhydroquinone-3 mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized three new peptide-DMQ-MA conjugates: DMQ-MA-Arg-Arg-Ome, DMQ-MA Lys(Cbz)-Arg-Ome, DMQ-MA-Lys(Cbz)-Arg-Arg-Ome; two new DMQ-MA-peptide Chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-Ome, DMQ-MA-Lys(DMQ-MA) Lys(CRB)-Arg-Ome and four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys(DMQ MA)-Phe-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Ile-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Val-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-Ome. These conjugates were synthesized by coupling protected amino acid residues according to Pfp/DCC methods (Pfp: Pentafluorophenol, DCC:N,N'-Dicyclohexyl-carbodiimide) in solution. After deblocking the Boc- group of the Lysine, the conjugation was achieved by reaction with the pentafluorophenyl ester of DMQ-MA in DMF. The CRB in the side chain was coupled by deblocking the lysylcarbobenzyloxy protecting group Cbz and then reacting with the pentafluorophenyl ester of Chlorambucil(CRB). Further studies on cytotoxicity and sequence specificity of DNA alkylation of these five new conjugates are being investigated. PMID- 11765905 TI - Cytosolic and non-cytosolic carbonic anhydrase enzymes from bovine leukocytes. AB - In this study, carbonic anhydrase (CA) enzyme has been purified and separately characterized according to bound form in 4 steps as outer peripheral, cytosolic, inner peripheral, and integral from bovine leukocyte. Affinity chromatography has also been used for purification of the enzyme in four steps. CA has been found for each step. Measurment of enzyme activity has been done by CO2 hydratase activity and esterase activity methods. Optimum pH and optimum temperature have been defined for each step of purified enzyme. The behaviors of CA with specific inhibitors, such as KSCN and NaN3 have been investigated. In each step, molecular weight and purity have been determined by gel filtration and SDS-PAGE electrophoresis. In addition, enzyme K(M) and Vmax values have been determined with the method of Lineweaver-Burk. PMID- 11765906 TI - A review of residential radon case-control epidemiologic studies performed in the United States. AB - Lung cancer is the leading cause of cancer death in the United States for both men and women. Although most lung cancer deaths are attributable to tobacco usage, even secondary causes of lung cancer are important because of the magnitude of lung cancer incidence and its poor survival rate. This review summarizes the basic features and major findings from the published U.S. large scale residential radon case-control studies performed in New Jersey, Iowa, and Missouri (two studies). The methodology from an unpublished study covering Connecticut, Utah, and Southern Idaho is also presented. Overall, the higher categorical risk estimates for these published studies produced a positive association between prolonged radon exposure and lung cancer. Two studies (Missouri-II and Iowa) that incorporated enhanced dose estimates produced the most compelling evidence suggesting an association between prolonged residential radon exposure and lung cancer. The prevailing evidence suggests that the statistically significant findings may be related to improved retrospective radon exposure estimates. The general findings from the U.S. studies, along with extrapolations from radon-exposed underground miners, support the conclusion that after cigarette smoking, prolonged residential radon exposure is the second leading cause of lung cancer in the general population. PMID- 11765907 TI - Health risk assessment of urban suspended particulate matter with special reference to polycyclic aromatic hydrocarbons: a review. AB - Airborne suspended particulate matter is an important marker of air quality. The term 'particulates' includes organic and inorganic matter, nitrogen compounds, sulphur compounds, polycyclic aromatic hydrocarbons (PAHs), several heavy metals, and radionuclides. The health risks from the 'classic' pollutants sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, and particulates have been comprehensively reviewed. Alarming levels of non-classic pollutants like the PAHs have been reported globally. PAHs have been found in placental tissues of women and in umbilical cord blood samples from newborn babies. The damaged DNA in cord blood is a indication of the fate of these pollutants in the environment. Hence, a need exists for a comprehensive investigation of the human health-related aspects of exposure to particulates and PAHs in the urban environment. This paper reviews the literature on PAHs in conjunction with particulate matter on a global perspective. PMID- 11765908 TI - Xenobiotic considerations for the development of autoimmune liver diseases: bad genes and bad luck. AB - The etiologic origins of autoimmune disease remain an enigma. Although considerable information on the mechanisms of immunopathology has been acquired, in part from murine models, such mechanisms have yet to be substantiated in human autoimmune disease. This absence of validation is especially true for organ specific diseases like those affecting the liver. In this review we focus on the putative role of xenobiotics as inducing agents for autoimmune liver pathology. In particular, we discuss the autoantibody immune response, the humoral hallmark of autoimmune disease, as well as cellular immune responses. We believe that exposure to environmental factors, namely xenobiotics, is the initiating straw that breaks the camel's back, leading to the loss of tolerance to self proteins in genetically susceptible hosts. The end result is a perpetuating process that is determined by the governing features of the genetics of the host and by exposure to the inciting environmental agent. Interestingly, the liver, an organ that plays a major role in immune tolerance, can itself become the target of autoreactivity and immune destruction. PMID- 11765909 TI - Physicochemical and bacteriological assessment of water quality at the Ross Barnett reservoir in central Mississippi. AB - The Ross Barnett Reservoir serves as a source of water supply for the city of Jackson, Mississippi, U.S.A. and is an important site for recreational activities for many residents of Mississippi counties. A broad spectrum of illness is associated with water-contact activities like bathing and swimming in recreational waters. In the present research, we assessed the bacteriological quality of water in the Ross Barnett Reservoir and compared the levels of bacteria with the recommended criteria for public health protection. From June 12, 1999 to October 2, 1999, we collected water samples weekly from two different sites in the reservoir and tested them for the following bacteriological parameters: heterotrophic plate counts, total coliforms, fecal coliforms, and fecal streptococci. The samples were also tested for basic physical and chemical characteristics of water. The results of the study indicate that the respective mean concentrations of bacteria (colony forming units per 100 mL of water) in water samples collected from the reservoir were 5.6 x 10(6)+/-1.5 x 10(6) (heterotrophic plate counts), 4.5 x 10(4) +/- 5.3 x 10(4) (total coliforms), 5.0 x 10(2) +/- 1.6 x 10(2) (fecal coliforms), and 9.1x10(1)+/-7.3x10(1) (fecal streptococci). The values of all physical and chemical parameters were at acceptable levels. The bacterial densities, however, often exceeded federal/state guidelines by several orders of magnitude, raising considerable public health concerns. Steps should therefore be taken to develop and implement strategies to improve the water quality and to reduce or eliminate the potential health risks associated with water-contact activities in the Ross Barnett Reservoir. PMID- 11765910 TI - Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case-control study in Poland. AB - The purpose of the study was to assess the relation between the simultaneous exposure to alcohol and consumption of micronutrients that have protective properties against colorectal cancer. A hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 at the University Hospital in Krakow, Poland. In total, 180 incident cases of colorectal cancer, confirmed by histopathology, were recruited and an equal number of controls, individually matched by gender and age (+/-5 y), were chosen amongst patients with no history of cancer. A food-frequency questionnaire for 148 food items, combined with the quantity of foods eaten, was used to assess the normal dietary pattern. The data confirmed the reported inverse association between the intake of retinol, thiamine, or antioxidant micronutrients (vitamins C, E) and the occurrence of colorectal cancer. Alcohol intake was found to be an important risk factor for this cancer site, and the risk escalated in parallel with increased intake of retinol, carotene, vitamins C and E, but with high consumption of alcohol ran a noticeably high risk of colorectal cancer (OR= 6.79; 95% CI: 2.08-22.18). The risk was markedly lower, however, among alcohol drinkers who reported a high intake of micronutrients (OR = 1.35; 95% CI: 0.39-4.67). The data suggest that a combination of high consumption of alcohol and low intake of retinol and antioxidant vitamins may considerably increase the risk of colorectal cancer. PMID- 11765911 TI - The measles virus (MV) glycoproteins interact with cellular chaperones in the endoplasmic reticulum and MV infection upregulates chaperone expression. AB - The present study examines the coprecipitation of measles virus (MV) glycoproteins with host cell endoplasmic reticulum (ER) chaperone proteins. Both the haemagglutinin (H) and fusion (F) glycoproteins interacted with calnexin and GRP78, whereas interaction with calreticulin was only demonstrated for the H glycoprotein. The alpha-glucosidase inhibitor castanospermine reduced and delayed the association of F proteins with calnexin. We have previously shown that alpha glucosidase activity is important for the functionality and antigenicity of the MV F glycoprotein and for release of MV particles from infected cells. Thus, interaction with calnexin appears vital for processing of nascent MV F protein into its functional conformation. In contrast to many other viral glycoproteins, a substantial proportion of the pulsed MV glycoproteins remained associated with ER chaperones for more than 2(1/2) h. Thus, the slow and incomplete migration of MV glycoproteins to the cell surface may result from their retention by ER chaperones, probably due to malfolding. MV infection upregulated the cellular expression of calreticulin and GRP78 and also increased their presence at the cell surface. The chaperone proteins are involved in a wide range of cellular processes, and their induction by MV may play a role for the pathogenesis of measles and its sequelae. PMID- 11765912 TI - Identification of a promoter in position 56 within the long control region of human papillomavirus type 18. AB - The expression of the oncogenes E6 and E7 of the cervical cancer associated human papillomavirus type 18 was shown to be directed from the promoter in position 105 (P105), which is reportedly the only early promoter located within the long control region (LCR). However, in C33A cells transiently transfected with a reporter construct containing the LCR of HPV18 in front of the luciferase gene a transcript initiating at position 56 was present in addition to those initiating from the P105. A perfect TATA Box consensus sequence 30 bp further upstream, which is highly conserved among HPVs associated with cervical cancer, was required for the activity of this novel promoter, denoted here as P56. The P56 specific transcript obviously depends on promoter downstream sequences, since transcripts initiating from the P56 were not present when the CAT gene was cloned downstream of the LCR. We detected transcripts initiating from both the P105 and the P56 in primary keratinocytes harboring episomal HPV18 as well as in the HPV 18 positive cervical carcinoma cell lines HeLa, C4-1 and SW756. Our data suggest that in HPV18, the expression of the early viral proteins including the oncogenes might be directed from a second promoter, located within the LCR. PMID- 11765913 TI - Completion of nucleotide sequence and generation of highly infectious transcripts to cucurbits from full-length cDNA clone of Kyuri green mottle mosaic virus. AB - The nucleotide sequence of the genome of the type strain of Kyuri green mottle mosaic virus (KGMMV-C1) has been completely determined. The genome structure and sequence of the virus were compared to those of Yodo strain of KGMMV (KGMMV-Y). The genome of KGMMV-C1 is 6,514 nucleotides long consisting of 5' and 3' nontranslated regions (NTRs) and four open reading frames coding for 131 kDa and 189 kDa viral replicases, 28 kDa movement protein and 17 kDa coat protein. The nucleotide and amino acid sequences identities of the four encoded proteins and two NTRs between KGMMV-C1 and KGMMV-Y were 85.6% to 93.9% and 87.6% to 95.5%, respectively. Full-length cDNA of KGMMV-C1 was directly amplified by reverse transcription polymerase chain reaction (RT-PCR) with a set of S'-end primer anchoring T7 RNA promoter sequence and 3'-end primer. This full-length RT-PCR product allowed RNA to be transcribed in vitro. The T7 promoter-anchored RT-PCR product was cloned and used as templates for transcription for plant inoculation test. Capped transcript RNAs transcribed from the full-length cDNA clone as well as capped transcript RNAs from the uncloned RT-PCR products were infectious and caused symptoms characteristic of KGMMV when mechanically inoculated to systemic host plants such as zucchini squash, cucumber and Nicotiana benthamiana. Transcript-derived progeny virus was indistinguishable from the wild-type virus with the same biological and biochemical properties. To our knowledge, this is the first report of the generation of a biologically active KGMMV clone, driven by the T7 promoter, that is highly infectious to cucurbitaceous plants. PMID- 11765914 TI - New JC virus (JCV) genotypes from papua new guinea and micronesia (type 8 and type 2E) and evolutionary analysis of 32 complete JCV genomes. AB - The JC virus (JCV) is a ubiquitous human polyomavirus that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large percentage of the population. Geographic-specific JCV variants, isolated from urine and from brain of progressive multifocal leukoencephalopathy (PML) patients, have been grouped into seven distinct genotypes based on whole genome analysis and by individual polymorphic nucleotides (typing sites) in the VP1 coding region. Mutations in the archetypal regulatory region, sometimes consisting of deletions and/or duplications, are also useful taxonomic characters for further characterizing and subdividing genotypes. Investigation of JCV variation in Papua New Guinea (PNG) revealed three distinct variants called PNG- 1, PNG-2, and PNG-3. These variants exhibited consistent coding region and regulatory region mutations. Evolutionary analysis of 32 complete JCV genomes including six new viral genomes from the western Pacific suggests that the new PNG JCV variants are closely associated with the broad group of Type 2 strains of JCV found throughout Asia, forming a monophyletic group with the Northeast Asian strains (Type 2A). Within the Type 2 clade, however, the PNG JCV variants cluster as two distinct groups and are therefore described here as new JCV genotypes designated Type 2E and Type 8. PMID- 11765915 TI - Genetic classification of "Sapporo-like viruses". AB - "Sapporo-like viruses" (SLVs) and "Norwalk-like viruses" (NLVs) are an important cause of acute gastroenteritis in humans. While NLVs have been genetically classified into three major genetic groups consisting of 17 genetic subgroups, a classification of SLVs into comparable genetic groups remains to be determined. In an attempt to classify both SLVs and NLVs uniformly, the sequences of 2 SLV strains newly detected from French infants were analysed together with the published sequences of 9 SLV and 19 NLV strains. Distance and phylogenetic analyses were conducted on the sequences of the capsid gene, RNA polymerase gene, 3' open reading frame (3'ORF), ORF overlapping the capsid gene, and 3' untranslated region (3'UTR). The histogram showing frequency distribution of pairwise distances and the topology of the phylogenetic tree demonstrated that SLVs and NLVs could be classified uniformly on the basis of the entire capsid sequences and that the 11 SLV strains could be genetically classified into 3 major genetic groups, genogroups I, II and III, comprised of 5 genetic subgroups. The differentiation of the 11 SLV strains into these genetic groups was also maintained in the 4 remaining genome regions, while the sequences at the junction between the RNA polymerase and capsid genes were shown to be genogroup-specific. PMID- 11765916 TI - Rapid molecular analysis of the haemagglutinin gene of human influenza A H3N2 viruses isolated in spain from 1996 to 2000. AB - A simple molecular technique was used for the rapid preliminary genetic characterization of human influenza A H3N2 viruses isolated in Spain from 1996 to 2000. Subtyping, based on RT-PCR, was followed by subtype-specific restriction enzyme fragment length polymorphism (RFLP) analyses of an amplified region of the HA1 domain of the H3 haemagglutinin (HA) gene to distinguish variants differentiated by common amino acid substitutions in HA1. The approach was tested using 135 Spanish H3N2 isolates and included nucleotide sequencing and phylogenetic analyses of a region of the HA1 domain of 41 representative isolates. The viruses were distinguished by haemagglutination inhibition (HI) assays into two antigenically discernible groups, the A/Wuhan/359/95-like and A/Sydney/5/97-like viruses. The results of PCR-RFLP analysis allowed a finer classification into five genetic variant subgroups, corresponding to those distinguished by phylogenetic analyses. This rapid, simple and variant-specific procedure could, therefore, be used to rapidly screen clinical specimens prior to more detailed antigenic and genetic analyses. PMID- 11765917 TI - Identification of apoptosis-inhibiting gene in Leucania separata nuclear polyhedrosis virus. AB - A novel gene lsp40 from leucania separata nuclear polyhedrosis virus (LsNPV) which was homologous to the p35 gene from Autographa californica Nuclear Polyhedrosis Virus (AcNPV) was localized in the EcoRV-5.5 kb fragment of LsNPV genome DNA and was sequenced. The open reading frame (ORF) of lsp40 was 906 bp long and encoded an approximately 40 kDa peptide consisting of 302 amino acid residues. The Isp40 shares 80.4% and 70.4% identity of nucleotide and amino acid sequence, respectively, to the AcNPV-p35 gene. The identity in promoters of both genes was as high as 100%. It was found that there were two TATA and GC boxes, three ACGT motifs for initiation of early gene transcription and one typical TTAAG core sequence for initiation of late gene transcription at both gene's 5' end, and two AATAAA tail signals at 3' end. The Isp40 started to express 2 hours after being transfected into the Ls cells to produce an approximately 40 kDa protein. The expression of the lsp40 gene might also inhibit the apoptosis of the Ls cells induced by removing serum. The expression of lsp40 in Vero cells delayed the apoptosis of the Vero cells induced by poliovirus infection. The lsp40 gene rescued vAcAnh (a kind of AcNPV p35-deletion mutant) in the Sf9 cells resulting in inhibition of the apoptosis and production of polyhedra. All these data suggested that the lsp40 gene was a homologous and functional gene similar to AcNPV p35 gene. PMID- 11765918 TI - Transcription and temporal cascade in Chilo iridescent virus infected cells. AB - Chilo iridescent virus (CIV) is the type species for genus Iridovirus, and belongs to the family Iridoviridae. Members of this family are large, isometric, cytoplasmic DNA viruses. Our laboratory has established that CIV replicates productively in the cotton boll weevil, Anthonomus grandis. Given the economic importance of this host and the dearth of knowledge on this virus, we have initiated host-virus interaction and molecular studies on CIV. This report focuses on regulation of transcription in CIV infections. We carried out northern analyses on total cellular RNA from infections of IPRI-CF-124T cells, using a complete genomic library of CIV and several putative gene-specific probes. Our data show a temporal cascade based on analysis of 137 detectable transcripts comprising 38 immediate-early (IE), 34 delayed-early (DE), and 65 late (L) transcripts. Analysis with gene-specific probes supported the cascade pattern. Both helicase and RNA polymerase were immediate-early; major capsid protein was late. The CIV gene expression cascade appears to operate primarily at the transcriptional level. Temporal classes observed are consistent with earlier studies at the polypeptide level and with transcriptional patterns in frog virus 3, genus Ranavirus in the Iridoviridae. Our results provide an important basis for understanding mechanisms driving the CIV temporal cascade. PMID- 11765919 TI - Evidence that the proliferation stage of micropropagation procedure is determinant in the expression of banana streak virus integrated into the genome of the FHIA 21 hybrid (Musa AAAB). AB - Banana streak virus (BSV) is causing increasing concern in almost every producing area of banana and plantain (Musa spp.) worldwide. This situation appeared partially linked to some breeding lines and micropropagated hybrids. A complete BSV sequence integrated into the genome of a triploid plantain has been recently characterised and it has been hypothesised that it could give rise to infectious virus via recombination. In this study, we evaluated the effect of a routine micropropagation procedure on the expression of BSV in the FHIA 21 tetraploid hybrid. The widespread presence of integrated sequences and the absence of episomal BSV in thirty FHIA 21 "mother plants" selected for micropropagation were first confirmed by specific PCR and IC-PCR tests. The proliferation stage of the procedure, characterised by an intensive production of neoformed buds, appeared determinant in BSV expression whereas the rooting and acclimatisation stages had little or no effect. The duration in culture and the way of subdividing the clumps of proliferation influenced greatly the percentage of episomal BSV infections, reaching 58% of infected micropropagated lines after six in vitro subcultures. These data suggest that the expression of episomal BSV observed during the in vitro procedure is correlated with the presence of an integrated form. PMID- 11765920 TI - Effect of deletion and the site of insertion in double copy anti-tat retroviral vectors: viral titres and production of anti-tat mRNA. AB - In attempts to further develop murine leukemia virus (MLV) based retroviral vectors for gene therapy, we investigated vector production and antisense expression from retroviral constructs with U3 deletions or insertions. Promoter elements in the U3 region of the 3' LTR of the vector pLXSN were deleted and replaced with DNA encoding the HIV anti-tat gene under control of the tRNAmet promoter to produce a double copy self inactivating vector (DC-SIN). DC-SIN constructs were compared to vectors containing the anti-tat cassette inserted at 5 different sites of the U3 region (DC-insertions). Titres of DC-SIN and DC insertion vectors were similar but approximately 10 fold lower than parental pLXSN. Cells transduced with DC-SIN and DC-insertion vectors all expressed anti tat mRNA. Transcripts from the MLV-LTR were detected in cells transduced with DC insertion but not DC-SIN vectors or a vector with the anti-tat cassette between CAAT and TATA boxes of the promoter, indicating inactivation of the viral promoter in the latter vectors. Cells transduced with constructs of either design showed comparable efficacy of protection against HIV challenge. Thus, no U3 insertion site was preferred for virus production. Insertion of a tRNA promoter between CAAT and TATA boxes and the DC-SIN design which would not introduce an active RNA pol II promoter into the genome are attractive for further development of safe gene therapy agents. PMID- 11765921 TI - The US2 gene product of herpes simplex virus type 2 interacts with cytokeratin 18. AB - In order to clarify the biological role of US2 gene product of herpes simplex virus type 2 (HSV-2), a HeLa cDNA library was screened in the yeast two-hybrid system using US2 protein as bait, and several interacting proteins were identified, including cytokeratin 18. US2 protein was co-immunoprecipitated with cytokeratin 18 from HSV-2 infected cell lysates. Analysis of infected orA431 cells by immunofluorescence showed that US2 protein gave filamentous or dot-like cytoplasmic staining pattern, and that it co-localized with cytokeratin 18. When US2 protein was expressed alone, it co-localized with cytokeratin 18. To define the domain interacting with cytokeratin 18, deletion mutant proteins were constructed and cells transfected with mutants were analyzed by indirect immunofluorescence. These results suggest that the N-terminal half of the US2 protein, especially the region containing amino acids 42-77, is important for interaction with cytokeratin 18. PMID- 11765922 TI - Rat cytomegalovirus open reading frame R44 is an early-late gene that encodes a nuclear protein. AB - Rat cytomegalovirus (RCMV) open reading frame R44 is the homolog of human cytomegalovirus gene UL44, which encodes the DNA polymerase accessory protein. Here, we show that R44 is transcribed as a 3.6-kb mRNA within the early and late phases of infection in vitro. In order to find potential monoclonal antibodies (MoAbs) directed against the R44-encoded protein (pR44), a panel of anti-RCMV MoAbs was screened for binding to pR44 recombinant proteins. Thus, an anti-pR44 MoAb, termed RCMV8, was identified. By using this MoAb, pR44 could be detected as early as 8 h after RCMV infection in vitro. The pR44 protein was determined to have a molecular mass of approximately 55 kDa and was found to be localized to the nucleus of RCMV-infected cells. PMID- 11765923 TI - Inhibition of apoptosis by primary isolates of herpes simplex virus. AB - HSV-1 inhibits apoptosis of the infected cell, presumably to increase viral yield. Weaker anti-apoptotic activity was previously reported in laboratory adapted HSV-2, but not in two low-passage clinical HSV-2 isolates, suggesting that the anti-apoptotic effect might result from adaptation to laboratory growth. We therefore assembled a large panel of clinical strains of HSV-1 and HSV-2. Clinical and laboratory strains of HSV-1 strongly inhibited apoptosis of Jurkat cells, as determined by morphologic change or caspase activation, while clinical HSV-2 strains showed no inhibitory activity in Jurkat cells. These findings suggest fundamental differences between HSV-1 and HSV-2 in their manipulation of host cell apoptosis. PMID- 11765924 TI - Entry of influenza virus into a glycosphingolipid-deficient mouse skin fibroblast cell line. AB - A glycosphingolipid (GSL)-deficient mouse skin fibroblast mutant cell line (GM95) was tested for its susceptibility to influenza virus infection and/or fusion. Octadecyl rhodamine labeled influenza virus fused at 37 degrees C and low pH with GM95 cells at similar rates and extents as with the parental cell lines which did bear glycosphingolipids. Influenza virus infected the GM95 cells at the same level as the parental cell lines. The infection and fusion was blocked when the cell lines were pre-treated with neuramindase. We conclude that influenza virus uses mainly sialoglycoproteins and that gangliosides are not essential for influenza virus fusion and infection. PMID- 11765925 TI - Cultures of equine respiratory epithelial cells and organ explants as tools for the study of equine influenza virus infection. AB - Equine nasal turbinate epithelial cells and tracheal rafts were maintained with sustained viability in culture. Both types of culture supported productive replication of equine influenza virus (equine-2, subtype H3N8) and cell death occurred through apoptosis following viral infection. Thus, primary respiratory epithelial cell and organ cultures of equine origin may be valuable as alternatives to the intact animal for studying the virus-host interaction of equine respiratory viruses including influenza. PMID- 11765926 TI - Potato yellow mosaic virus: a synonym of tomato yellow mosaic virus. AB - Tomato yellow mosaic was first described in 1963, as a disease caused by a geminivirus transmitted by the whitefly Bemisia tabaci in Venezuela. In 1981 and 1985, Tomato yellow mosaic virus (ToYMV) was reported to occasionally infect potato plants growing in the proximity of tomato plantings affected by this virus. Despite these previous reports, a virus isolated from yellow mosaic affected potato plants in Venezuela, was described in 1986 as a "new geminivirus" called potato yellow mosaic virus (PYMV). In recent years, different geminiviruses related to PYMV have been described from tomato fields in Venezuela and other countries in the Caribbean Basin, including Panama. Comparative nucleotide and amino acid sequence analyses of a 1698 bp fragment amplified from the common region and part of the AV1 and AC1 ORFs of ToYMV from Venezuela, yielded 95.7% sequence identity with the corresponding regions of PYMV. Nucleotide and amino acid sequence identities between ToYMV and PYMV, were 96.3% and 95.1% for AC1, and 95.7% and 100% for AV1, respectively. The identity of the nucleotide sequence for the common region of ToYMV and PYMV was 96.5%. Comparative sequence analyses conducted with ToYMV and other tomato begomoviruses present in the Caribbean region, showed only distant relationships. It is concluded here that PYMV is a synonym of ToYMV. PMID- 11765927 TI - Classifying reverse transcribing elements: a proposal and a challenge to the ICTV. International Committee on Taxonomy of Viruses. PMID- 11765928 TI - Pellagra and some allied conditions. 1928. PMID- 11765929 TI - Penicillin in suppurative disease of the lungs: a report of three cases. 1943. PMID- 11765930 TI - The yeast-like fungi of the human vagina. 1938. PMID- 11765931 TI - Comparative statistical analyses of the 1916 and 1931 epidemics of poliomyelitis in and about the city of New Haven. 1932. PMID- 11765932 TI - Comments on immunity to virus diseases. 1944. PMID- 11765933 TI - Poliomyelitis: problems in pathogenesis and immunization. 1957. PMID- 11765934 TI - The case for live poliovirus vaccination. 1960. PMID- 11765935 TI - Recent studies with EB virus. 1975. PMID- 11765936 TI - Non-A, non-B hepatitis. 1976. PMID- 11765937 TI - The failure of the 1976 swine influenza immunization program. 1977. PMID- 11765938 TI - Creatine and creatinine. 1932. PMID- 11765939 TI - The swine influenza program. 1977. PMID- 11765940 TI - Psychiatrists, neurologists, and the neurosurgeon. 1934. PMID- 11765941 TI - Prefrontal lobes and social development. 1950. PMID- 11765942 TI - Creating a chimpanzee community. 1963. PMID- 11765943 TI - Artificial radio-activity and neutron rays in biology and medicine. 1937. PMID- 11765944 TI - On the physiological significance of choline esterase. 1939. PMID- 11765945 TI - The rapid production of tumors by two new hydrocarbons. 1939. PMID- 11765946 TI - Genetic nature of the constitutional states of cancer susceptibility and resistance in mice and men. 1945. PMID- 11765947 TI - The study of serum proteins and lipids with the aid of the quantity ultracentrifuge: VII. Some features of a system of lipoproteins which contain phospholipid but no free cholesterol. 1952. PMID- 11765948 TI - The significance of fever in infections. 1954. PMID- 11765949 TI - The determination of chromosomal sex by oral smears. 1956. PMID- 11765950 TI - Organizing interstitial pneumonia: definition of the lesion and attempts to devise an experimental model. 1968. PMID- 11765951 TI - Lack of effect of salicylate on pyrogen release from human blood leucocytes in vitro. 1973. PMID- 11765952 TI - Recent advances in the understanding of acupuncture. 1978. PMID- 11765953 TI - The distribution and movement of water and solutes in the human body. 1933. PMID- 11765954 TI - Feline preleukemia: an animal model of human disease. 1978. PMID- 11765955 TI - The passing of Harvey Cushing. 1939. PMID- 11765956 TI - Daniel Webster and the hay-fever. 1937. PMID- 11765957 TI - The place of Vesalius in the culture of the Renaissance. 1944. PMID- 11765958 TI - Adapting Man Adapting: curing, helping, consoling. 1979. PMID- 11765959 TI - The World Health Organization. 1947. PMID- 11765960 TI - A national science foundation. 1948. PMID- 11765961 TI - Industrial medical services for small industries. 1943. PMID- 11765962 TI - The mind and morality of the doctor. II. The physician and the macrocosm. 1965. PMID- 11765963 TI - Partners or protagonists: Congress and the academic medical centers. 1974. PMID- 11765964 TI - A system for cost and reimbursement control in hospitals. 1976. PMID- 11765965 TI - Renal changes in hypertension. 1935. PMID- 11765966 TI - The roentgenological survey of the pelvis. 1941. PMID- 11765967 TI - Dermatoglyphics: significant patternings of the body surface. 1946. PMID- 11765968 TI - Localized collapse of the lung by means of an extrapleural balloon. 1930. PMID- 11765969 TI - The theory and practice of natural childbirth. 1953. PMID- 11765970 TI - The hemagglutination test in rheumatoid arthritis. 1. Use of red cell pattern as endpoint in the method. 1956. PMID- 11765972 TI - Protein catabolism in suckling and fasting northern elephant seal pups (Mirounga anglstirostris). AB - Nursing elephant seal pups are hypothesized to be preadapted to the postweaning fast, yet no comparison of lipid or protein use for meeting metabolic costs has been made between these contrasting nutritional periods. To address this, protein catabolism was estimated in five elephant seal pups from measurements of urea turnover made twice during nursing and twice during the postweaning fast. Changes in body composition were measured in ten separate weaned pups via tritiated water dilution and matched to fasting urea turnover measurements in order to assess errors in protein catabolism derived from urea turnover rates. Estimates of lean mass loss based upon urea turnover and tritiated water dilution were in general agreement, supporting estimates of protein catabolism derived from urea turnover measurements. Protein catabolism was estimated to contribute less than 4% to the average metabolic rate of suckling and fasting pups implying strict protein conservation during both periods and supporting the shypothesis that suckling pups are pre-adapted to fasting. It is proposed that strict protein conservation across suckling and fasting compensates for relative reductions in maternal investment associated with the abbreviated lactation period of the elephant seal. PMID- 11765971 TI - The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). AB - The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin 1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output. PMID- 11765973 TI - Seasonal changes in the thermoenergetics of the marsupial sugar glider, Petaurus breviceps. AB - Little information is available on seasonal changes in thermal physiology and energy expenditure in marsupials. To provide new information on the subject, we quantified how body mass, body composition, metabolic rate, maximum heat production, body temperature and thermal conductance change with season in sugar gliders (Petaurus breviceps) held in outdoor aviaries. Sugar gliders increased body mass in autumn to a peak in May/June, which was caused to a large extent by an increase in body fat content. Body mass then declined to minimum values in August/September. Resting metabolic rate both below and above the thermoneutral zone (TNZ) was higher in summer than in winter and the lower critical temperature of the TNZ occurred at a higher ambient temperature (Ta) in summer. The basal metabolic rate was as much as 45% below that predicted from allometric equations for placental mammals and was about 15% lower in winter than in summer. In contrast, maximum heat production was raised significantly by about 20% in winter. This, together with an approximately 20% decrease in thermal conductance, resulted in a 13 degrees C reduction of the minimum effective Ta gliders were able to withstand. Our study provides the first evidence that, despite the apparent lack of functional brown adipose tissue, sugar gliders are able to significantly increase heat production in winter. Moreover, the lower thermoregulatory heat production at most TaS in winter, when food in the wild is scarce, should allow them to reduce energy expenditure. PMID- 11765974 TI - Food consumption and body composition in mice selected for high wheel-running activity. AB - The effects of genetic selection for high wheel running (13th generation) and prolonged access (8 weeks) to running wheels on food consumption and body composition were studied in house mice (Mus domesticus). Mice from four replicate lines selected for high wheel-running activity ran over twice as many revolutions per day on activity wheels as did mice from four replicate control lines. At approximately 49 days of age, all mice were placed individually in cages with access to wheels and monitored for 6 days, after which wheels were prevented from rotating for the "sedentary" individuals. During the experiment, five feeding trials were conducted and body mass was measured weekly. After 8 weeks, body composition was measured by hydrogen isotope dilution. Across the five feeding trials, mice in the "active" group (wheels free to rotate) consumed 22.4% more food than mice in the "sedentary" group (wheels locked); mice from the selected lines consumed 8.4% more food than mice from the control lines (average of all trials; body mass-corrected values). In females, but not males, we found a significant interaction between selection and wheel access treatments: within the "active" group the difference in food consumption between selected and control animals was greater than in the "sedentary" group. At the end of the study, mice from the "active" and "sedentary" groups did not differ significantly in body mass; however, mice from the selected lines were approximately 6% smaller in body mass. Estimated lean body mass did not differ significantly either between selected and control lines or between wheel-access groups (P>0.3). Mice from selected lines had lower total body fat compared to mice from control lines (P=0.05; 24.5% reduction; LSMEANS) as did mice from the "active" compared to "sedentary" group (P= 0.03; 29.2% reduction; LSMEANS). Under these conditions, a sufficient explanation for the difference in body mass between the selected and control lines was the difference in fat content. PMID- 11765975 TI - Thermoregulatory responses of two mouse Mus musculus strains selectively bred for high and low food intake. AB - We examined the thermoregulatory responses of male and female mice Mus musculus that had been divergently selected on voluntary food intake, corrected for body mass, to produce a high-intake and a low-intake strain. Resting metabolic rate was determined by indirect calorimetry (at 30 degrees C, 25 degrees C, 15 degrees C and 5 degrees C). Body temperature responses were measured in a separate group of mice in a parallel protocol. High-intake mice had significantly elevated body masses compared to low-intake mice in both sexes. Lower critical temperature in both strains appeared to be around 28 degrees C. At 30 degrees C there was a significant strain effect on resting metabolic rate, with high strain mice having greater metabolism than low strain mice. Sex and body mass were not significant main effects on resting metabolic rate and there were no significant interactions. Body temperature measured at 30 degrees C, 25 degrees C, 15 degrees C and 5 degrees C differed significantly between sexes (females higher) and there was a significant sexxbody mass interaction effect, but there was no difference between strains. Thermal conductance was significantly related to strain and sex, mice from the high strain and males having greater thermal conductances than mice from the low strain and females. Artificial selection has resulted in high-intake mice having greater body masses and greater thermal conductances, which together account for up to 45% of the elevated daily energy demands that underpin the increase in food intake. The greater levels of food intake were also associated with higher resting metabolic rates at 30 degrees C. PMID- 11765976 TI - Developmental and acclimatory contributions to water loss in a desert rodent: investigating the time course of adaptive change. AB - Understanding the evolution of physiological traits requires considering three nonexclusive mechanisms that underlie phenotypes and cause their change over different time scales: acclimation, developmental plasticity, and natural selection for genetically fixed traits. Physiological adjustments to changes in the desiccating potential of the environment were investigated with one subspecies of common desert rodent, Dipodomys merriami merriami (Merriam's kangaroo rat). We raised young whose parents originated from environments that differ in both temperature and humidity. These young were raised under either desiccating or water-abundant conditions, and their water loss was measured at a series of temperatures to determine the effect developmental conditions have on resistance to desiccation. We then determined the contribution of acclimation to desiccation resistance by keeping the differentially raised young in conditions opposite to those during their development and again measuring water loss. We found that developmental plasticity and acclimation can completely account for the existing intraspecific variability in desiccation resistance under certain conditions. In fact, developmental and acclimatory changes can equal genetically based differences of the populations. This phenotypic plasticity can operate relatively quickly and therefore may attenuate the actions of natural selection. Understanding the extent and nature of such flexibility is critical to our understanding intraspecific variability and the consequences of changing climate. PMID- 11765977 TI - Ammonia uptake and its effects on ionoregulation in the freshwater crayfish Pacifastacus leniusculus (Dana). AB - Exposure of adult crayfish Pacifastacus leniusculus to Artificial Freshwater (AFW) media containing 1.5 m and 0.15 mmol x l(-1) total ammonia [Tamm; 0.1 x acute lethal concentration (24 h LC50) and 0.01 x 24 h LC50] and adjusted to pH 6.5, pH 8.2 and pH 10.5 resulted in significant increases in haemolymph ammonia over a 24-h period. Ammonia accumulated most rapidly at pH 10.5. These media were chosen to expose animals to a range of different un-ionised ammonia (UIA) [NH3] and ionised ammonia [NH4+] concentrations. From comparisons of measured transepithelial potential differences (PDte) with calculated Nernst potentials (PDNH4+) for the known haemolymph-to-medium gradients of [NH4+], it was deduced that, in pH 8.2 and pH 6.5 AFW, NH4+ was not in thermodynamic equilibrium across the integument (presumably gill epithelium). In pH 10.5 AFW with 1.5 mmol x l(-1) Tamm (predominantly NH3), the accumulation of ammonia in the haemolymph was in the NH4+ form due to haemolymph pH regulation by the crayfish in this alkaline external medium. Measured net fluxes of ammonia (Jamm(net)) were inwardly directed and maximal when [NH3] was the main component externally, but were also significant at pH 8.2 with high [NH4+] ([NH4+]:[NH3] approximately 20:1). Haemolymph Na+ depletion was significant and, over the 24-h exposure period, most rapid in high [NH3] medium but [Cl-] was unaffected. However, paradoxically, sodium uptake (measured JNa(in) on immediate transfer to high Tamm medium) was not significantly inhibited when [NH3] was the predominant ammonia species. In 1.5 mmol x l(-1) Tamm (mainly [NH4+), VNa(in) (the active component of JNa(in)) was significantly inhibited, particularly at low external [Na+]. This inhibition could not be demonstrated as one of competition at an Na+/NH4+ apical gill exchange site. The resultant net efflux of sodium from the animal showed that the ability of the animals to balance sodium losses at low external [Na+] was severely affected. Longer exposure to pH 10.5 AFW with high [NH3] (12 h) resulted in significantly increased JNa(out), while not significantly affecting JNa(in). Analysis of urinary Na+ losses showed that, while urinary flow rate and water reabsorption was most likely unaffected by ammonia exposure, final urine [Na+] was significantly elevated. The resulting urinary Na+ loss accounted for 63% of the increased JNa(out) in high [NH3] medium. PMID- 11765978 TI - Modulators of haemocyanin oxygen affinity in the hypoxia- and sulphide-tolerant Baltic isopod Saduria entomon (L.). AB - Dialysed haemocyanin from the isopod Saduria entomon had a considerably increased oxygen affinity (lower P50) and Bohr factor (-1.71) compared to native haemocyanin (Bohr factor -1.36) indicating that dialysis removes a small molecule size modulating factor decreasing the affinity of native haemolymph. Dialysed haemocyanin had a slightly lower co-operativity (2.42 +/- 0.3) than native haemocyanin (2.9 +/- 0.2). L-Lactate (10 mmol l(-1)) improved oxygen affinity by 1-1.5 torr while urate had no effect. Mg2+ affected affinity in a pH-dependent manner (Bohr-factor increased to -1.67) while Ca2+ had no effect on the Bohr factor but increased affinity with ca 1 torr. Thiosulphate changed the Bohr factor to -1.75 to -1.82, similar to dialysed blood. Co-operativity was in neither case affected. The haemocyanin characteristics of S. entomon are similar to those of crustaceans from hydrothermal vents. These characteristics are probably general for crustaceans that are more or less permanently exposed to sulphide. PMID- 11765979 TI - Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks. AB - Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone. PMID- 11765980 TI - Characteristics of dyslexia in a Dutch family. AB - This study investigates the characteristics of 19 members of a Dutch family. Nine of them, recognized as dyslexic in their early years, are compared with six non dyslexic members, whereas four form a non-classified category. From their personal histories, it is clear that the dyslexics had a long and troublesome educational career, while the non-dyslexics did not. However, probably because the dyslexic members had considerable intellectual resources and talents in mathematics and technical skills, most succeeded in getting degrees of a reasonably high standard and jobs that more or less matched their talents. In cognitive terms, differences in non-word processing, independent of response mode (reading, spelling, oral repetition), and in speeded word reading suggest stable deficits in phonological processing and in task-specific automatization. The spelling of words was fairly accurate, possibly because compensatory strategies were used, also indicated by remarks of the dyslexic members. Outside the reading and spelling area, only small and non-significant differences appeared in tasks tapping verbal short-term memory, rapid naming and working memory. However, the predicted discrepancy between the conceptual and the sequential factor of the Wechsler intelligence test was shown by most dyslexics. Two of the four non classified members of the family, who could not be classified as dyslexic because no early diagnosis was made, but had experienced learning problems at school, showed more or less the same characteristics, but were less successful at school and in society. In the discussion, the use of a family control group in studies with a large age range is recommended. PMID- 11765981 TI - Are RAN- and phonological awareness-deficits additive in children with reading disabilities? AB - The double-deficit hypothesis (Wolf, M. and Bowers, P.G. (1999) The double deficit hypothesis for the developmental dyslexias. Journal of Educational Psychology, 91, 415-438) proposes that deficits in phonological processing and rapid automatized naming (RAN) are separable sources of reading dysfunction. Further, the double-deficit hypothesis predicts that the presence of deficits in both phonological processing and RAN have an additive negative influence on reading performance above and beyond that of a single deficit. The purpose of this study was to examine the additive nature of phonological awareness (PA)- and RAN-deficits on written language skill in children with reading disabilities (RD). Concurrent relationships between PA, RAN, and written language skills were examined in 476 children with RD, ranging in age from 8 to 18 years of age. Hierarchical regression analysis revealed that PA and RAN skill have an additive effect on a majority of the reading and spelling measures. When participants were classified into three deficit subtypes based on the double-deficit model (i.e. phonological-, rate-, and double-deficit), comparisons across the subtypes confirmed that individuals with double-deficits performed below the single deficit groups on both subtyping variables (RAN and PA) and all measures of written language. When the double- and single-deficit groups were matched on the subtyping variable (i.e. double- and rate-deficit groups matched on RAN and double- and phonological-deficit groups matched on PA) differences between the double- and rate-deficit groups remained in non-word reading, whereas differences between the double- and phonological-deficit groups remained in timed word recognition and reading comprehension. These results support an additive model in which RAN-deficits primarily affect tasks that require speeded/fluent response, and PA-deficits primarily affect tasks that emphasize phonological processing skill. Results are also presented that illustrate several statistical problems associated with the formation of deficit groups by dichotomizing the RAN and PA variables. PMID- 11765982 TI - Auditory perceptual processing in people with reading and oral language impairments: current issues and recommendations. AB - A popular hypothesis holds that specific reading disability (SRD) and specific language impairment (SLI) result from an impaired ability to process rapid and brief sounds. However, the results of experiments that have tested this hypothesis are incongruous. A number of factors could explain these contradictory findings, including the questionable reliability and validity of rapid auditory processing tasks, individual differences in the auditory processing abilities of SRD and SLI populations, the age of listeners, the quality of control groups, and the relationship between verbal and non-verbal auditory processing abilities. These issues highlight the need for future studies to (1) establish the reliability and validity of psychophysical tasks used to assess rapid auditory processing; (2) report the rapid auditory processing scores of individuals rather than just group means; (3) include a wide range of reading and spoken language tests to determine the literacy and oral language profile of people who demonstrate an auditory processing deficit; (4) include clinical comparison groups to determine whether a rapid auditory processing deficit is related specifically to written and spoken language impairments; and (5) examine the relationship between low-level non-verbal, verbal, and phonological processing abilities. PMID- 11765983 TI - IQ tests. PMID- 11765984 TI - Re: Critical response to dyslexia, literacy and psychology assessment. PMID- 11765985 TI - Re: Critical response to dyslexia, literacy and psychology assessment. PMID- 11765986 TI - Biosolids research--the need continues. PMID- 11765987 TI - Use of biodegradable dissolved organic carbon to assess treatment process performance in relation to solids retention time. AB - A biodegradable dissolved organic carbon (BDOC) method has been developed and used to analyze secondary- and advanced-treated wastewater effluents and to investigate correlations between residual organic content and the solids retention time (SRT). Conventional biochemical oxygen demand (BOD) bottles and a 28-day incubation period were used. Secondary wastewater effluents from Hawaii were found to contain between 9.0 and 14.0 mg/L of dissolved organic carbon (DOC), of which 23 to 35% was biodegradable in the 28-day BDOC test (from a survey of nine treatment plants). Bench-scale, continuous-flow activated-sludge biological reactors treating synthetic wastewater were operated at SRTs between 2 and 15 days, and effluent BDOCs were determined. A good BDOC prediction equation was developed that incorporates the initial DOC, the DOC remaining after 5 days, and the SRT of the system from which the sample originated. This equation can be used to determine the BDOC value using data that can be obtained during a conventional 5-day BOD test. The determined equation was found to be appropriate for some of the full-scale wastewater effluent survey data. PMID- 11765988 TI - Characterization of denitrification and nitrification in a step-feed alternating anoxic-oxic sequencing batch reactor. AB - This study was conducted to characterize the denitrification and nitrification in a bench-scale sequencing batch reactor operating with a three-stage, alternating anoxic-oxic sequence and step feed (SAOSBR) for treating synthetic wastewater. The results of long-term operation and dynamic studies showed that the SAOSBR increased the availability of organic matter in wastewater for exogenous denitrification in anoxic periods, and subsequently allowed nitrification to occur under a lower organic loading in oxic periods. Comparatively high kinetic rates of 1.2 to 6.6 mg nitrate/g mixed liquor suspended solids (MLSS) x h for denitrification and 1.0 to 2.8 mg nitrogen/g MLSS x h for nitrification were found in dynamic studies. With sufficient influent organics and alkalinity, complete denitrification and full nitrification could be achieved sequentially in the alternating anoxic and oxic periods, resulting in an average total nitrogen removal efficiency up to approximately 90%. Alkalinity recovery because of exogenous denitrification was experienced, and a minimum influent alkalinity to total Kjeldahl nitrogen (TKN) ratio of 2.4 was required to reach complete TKN removal. The pH value would be a better parameter other than oxidation-reduction potential or dissolved oxgyen to determine the completeness of nitrification and denitrification in the SAOSBR. PMID- 11765989 TI - Tracking sources of bacterial contamination in stormwater discharges to Mission Bay, California. AB - Sources of the indicator bacteria total coliform, fecal coliform, and enterococcus were investigated in stormwater flows discharging to Mission Bay, a heavily used aquatic park in San Diego, California. Stormwater flows were targeted because long-term receiving water monitoring of the bay indicated that wet weather discharges were the predominant source of bacterial contamination. Exceedences in water quality objectives for body contact recreation established by the State of California most often occurred in the east bay, where the least amount of circulation and largest quantities of stormwater discharges occur. Unlike the wet weather results, almost all of the 89 storm drains that discharge to the bay either did not have flowing fresh water or did not contain exceedingly high bacteria densities during dry weather. Upstream tracking during multiple storm events on two of the largest watersheds draining to the bay showed that sources of indicator bacteria were diffuse and widespread. Densities were as high at the head of each watershed as they were at the mouth, where both discharged to the bay. Every reach in each creek exceeded State of California water quality objectives and had densities similar to surface flows measured before they entered the separate municipal storm sewer system from urban land uses, such as residential, commercial, and industrial, as well as open lands. PMID- 11765990 TI - Temperature effects in treatment wetlands. AB - Several biogeochemical processes that regulate the removal of nutrients in wetlands are affected by temperature, thus influencing the overall treatment efficiency. In this paper, the effects of temperature on carbon, nitrogen, and phosphorus cycling processes in treatment wetlands and their implications to water quality are discussed. Many environmental factors display annual cycles that mediate whole system performance. Water temperature is one of the important cyclic stimuli, but inlet flow rates and concentrations, and several features of the annual biogeochemical cycle, also can contribute to the observed patterns of nutrient and pollutant removal. Atmospheric influences, including rain, evapotranspiration, and water reaeration, also follow seasonal patterns. Processes regulating storages in wetlands are active throughout the year and can act as seasonal reservoirs of nutrients, carbon, and pollutants. Many individual wetland processes, such as microbially mediated reactions, are affected by temperature. Response was much greater to changes at the lower end of the temperature scale (< 15 degrees C) than at the optimal range (20 to 35 degrees C). Processes regulating organic matter decomposition are affected by temperature. Similarly, all nitrogen cycling reactions (mineralization, nitrification, and denitrification) are affected by temperature. The temperature coefficient (theta) varied from 1.05 to 1.37 for carbon and nitrogen cycling processes during isolated conditions. Phosphorus sorption reactions are least affected by temperature, with theta values of 1.03 to 1.12. Physical processes involved in the removal of particulate carbon, nitrogen, and phosphorus are not affected much by temperature. In contrast, observed wetland removals may have different temperature dependence. Design models are oversimplified because of limitations of data for calibration. The result of complex system behavior and the simple model is the need to interpret whole ecosystem data to determine temperature coefficients. Temperature seems to have minimal effect on biochemical oxygen demand (0.900 < theta < 1.015) and phosphorus (0.995 < theta < 1.020) removal, and more significant effect on nitrogen removal (0.988 < theta < 1.16). In colder climates, there may be seasonal slowdown of treatment, which can decrease the overall treatment efficiency of constructed wetlands. PMID- 11765991 TI - Pipe friction head loss in transportation of high-concentration sludge for centralized solids treatment. AB - The objective of this study was to develop a method of predicting pipe friction head loss, which is a key factor in pipeline transportation of high-concentration sludge, thereby optimizing design for pipeline systems. The study involved both experimentation and analysis of pipeline transportation. Moreover, the study led to the representation of pipe friction head loss as functions of average velocity, transportation distance, pipe diameter, pipe interior roughness, and solids viscosity and temperature. PMID- 11765992 TI - Anaerobic migrating blanket reactor treatment of low-strength wastewater at low temperatures. AB - The feasibility of the compartmentalized anaerobic migrating blanket reactor (AMBR) was studied for the treatment of low-strength soluble wastewater under low temperature conditions. During an operating period of 186 days, a 20-L AMBR was fed nonfat dry milk substrate as a synthetic wastewater at low temperatures (15 and 20 degrees C). The concentration of the influent was constant at chemical oxygen demand (COD) and 5-day biological oxygen demand (BOD5) concentrations of 600 and 285 mg/L, respectively. The soluble COD (SCOD) removal efficiency was 73% at the end of the operating period (15 degrees C) at a 4-hour hydraulic retention time (HRT), while the total COD (TCOD) removal efficiency was 59%. At a 4-hour HRT, staged conditions promoted complete removal of propionic acid in the final compartments of the reactor. The specific methanogenic activity of granules increased slowly until the end of the operating time, improving the removal rate. Biomass was retained effectively, as evidenced by the solids retention time (SRT) that was always greater than 50 days even during step decreases of the reactor HRT from 12 hours to 4 hours. A long SRT also promoted system stability during changes in flow, which was observed by SCOD removal efficiencies staving greater than 70%. During a hydraulic stress test, the HRT was reduced from 4 hours to 1 hour for one day (24 HRTs) in which volatile suspended solids (VSS) in the effluent increased from an average background level of 8.7 g/d to 35 g/d and the SRT decreased from 50.5 days to 12.6 days. However, mixed liquor volatile suspended solids concentration decreased only by 1 g/L, and hence a similar COD removal efficiency and biogas production was found one day after the hydraulic stress (as compared to one day before the hydraulic stress). PMID- 11765993 TI - Analysis of statistical outliers with application to whole effluent toxicity testing. AB - In this analysis, low-value outliers were detected in five data sets obtained from laboratory records. The effect of removing the outliers by three methods data rejection (asymmetrical and symmetrical trimming and Winsorization) revealed that all three methods slightly increased the mean and reduced the variance of the data sets. These opposing effects on the results of a hypothesis test of means were examined in the context of passing or failing a regulatory requirement significant difference between effluent concentration and a control. Analysis by statistical resampling of one data set showed that while all data rejection methods reduced the level of Type II error in a hypothesis test of no difference in reproduction between a test concentration and a regulatory limit, asymmetrical trimming was the best in this regard. PMID- 11765994 TI - Evaluation of direct removal of nitrate with entrapped mixed microbial cell technology using ethanol as the carbon source. AB - Biological denitrification from simulated contaminated groundwater using ethanol as an external carbon source was investigated with an entrapped mixed microbial cell (EMMC) system. Ethanol was used as an external carbon source to serve both as the energy source for the nitrate removal reaction and substrate for microorganisms in the system. The hydraulic retention time and chemical oxygen demand (COD)/nitrogen ratio significantly affect nitrate removal performance and, therefore, must be monitored carefully to achieve high rates of nitrate and COD removal. The effect of packing ratios of carriers in the reactor on nitrate removal performance was also investigated. The removal of nitrate and COD in reactors with various carrier packing ratios (12, 22, and 35%) is not significantly different during steady-state operation. However, the start-up periods in these three reactors are significantly different. The highest packing ratio can result in a fast removal of nitrate during the start-up periods. Results of solids retention time (SRT) analysis indicate that a long SRT in the EMMC system contributes to the stable removal of nitrate and to fast start up of the system. The increase of SRT is related to the increase in days of operation, SRT is maintained at a level of more than 200 days. PMID- 11765995 TI - Evaluation of agricultural sediment load reductions using vegetative filter strips of cool season grasses. AB - Vegetative filter strips for controlling sediment generated from the bare ground (i.e., ground not protected by mulch or plant cover) were studied. Plots consisted of a 4.6-m clean-tilled upslope sediment source area and 12.2-m vegetative filter strip located downslope from the sediment source area. Vegetative filter strips consisted of pure stands of six adapted cool season grasses and two cereal grains. Sediment-laden runoff was transported into the upslope edge of each filter strip. Runoff samples were collected from the lower end of each plot and analyzed for nonflow weighted sediment concentration. The rate of advance of water through each vegetative filter strip was measured. Additional measurements were made to define the plant characteristics of each vegetative filter strip species. In general, planted vegetative filter strips resulted 68% reduction concentration of sediment in initial runoff from a 50 year, 24-hour storm event on prewetted soil. Crested wheatgrass and smooth bromegrass vegetative filter strips reduced water flow velocity an average of 217% compared with the clean-tilled control plot. The length of time that water remained in the vegetative filter strip modestly correlated with average sediment concentration in runoff that was 5.5 g/L and 5.0 g/L, respectively, compared with the control plot, which yielded 16.3 g of sediment/L of runoff. Under dry soil conditions, sediment concentration in runoff from bromegass and crested wheatgrass was reduced by an average of 85% compared with the bare control plot. Length of time for water to advance through the smooth bromegrass and crested wheatgrass vegetative filter strips increased an average of 325% compared with the length of time required to flow through the clean-tilled bare strip. PMID- 11765996 TI - Time-dependent retardation model for chemical oxygen demand removal in a subsurface-flow constructed wetland for winery wastewater treatment. AB - The relative success of chemical oxygen demand (COD) removal models to describe measured rates of COD removal in a pilot-scale constructed wetland designed for treatment of high-strength winery wastewater are evaluated using retention times determined from tracer studies. Not surprisingly, two-parameter residual and retardation models better fit the measured removal data than single-parameter, first-order decay models for wastewater at average COD loadings up to nearly 5000 mg/L. The residual and retardation models yielded nearly equivalent fits to the measured data. However, the retardation model had more consistent parameters for COD removal data across different depth levels in the constructed wetland and at different loadings, and a slightly smaller sum of least-squared errors. The retardation model seems to be appropriate for constructed wetland design because it allows a steady decrease in COD with increased treatment time rather than a constant residual COD (C*) value. From the least-squares optimization procedure used to estimate model parameters (a volumetric rate constant, Kv, range of 3 to 12 d(-1)), nonrealistic, or physically meaningless, large C* values (C* range of 23 to 450 mg COD/L) that were dependent on COD loading were obtained, potentially underestimating the constructed wetland system's actual winery wastewater treatment potential. The optimal parameters for the retardation model applied to the pilot-scale constructed wetland ranged from 9 to 12 d(-1) for the initial degradation rate constant, Ko, and 2 to 5 d(-1) for the time-based retardation coefficient, b. These values should be verified for full-scale field systems based on field measurements currently underway. PMID- 11765997 TI - Persistency of bacterial indicators in biosolids stabilization with coal fly ash and lime. AB - Alkaline coal fly ash and lime were tested for their effectiveness in pathogen removal from biosolids at different time intervals and temperatures. Coal fly ash at 10 and 35% w/w was mixed with dewatered biosolids and then the ash-biosolids mixture was mixed separately with 0, 1.1, 2.2, 4.4, 8.5, 11, and 18% calcium oxide (w/w on a dry weight basis) with and without heating to 55 degrees C. Total bacteria, salmonella, and total coliforms were monitored at various time intervals. Both ash-biosolids mixtures with or without lime amendment had a significantly lower total bacterial population than the biosolids control, but the residual indigenous bacterial flora in the ash and lime stabilized biosolids still maintained a population of greater than 10(4) g(-1) dry biosolids. Alkaline stabilized biosolids with a lime amendment rate greater than 8.5% could maintain pH greater than or equal to 12 for more than 2 hours, which effectively removed total coliforms and salmonella in the mixture. Heat treatment to 55 degrees C and a storage time of 14 days provided an added advantage resulting in a further reduction in pathogens for all treatments. It is recommended that 10% ash biosolids mixture should be amended with a minimum of 8.5% lime on a dry weight basis for at least 2 hours to achieve acceptable levels of salmonella and total coliforms to ensure no pathogenic risk following land application. PMID- 11765998 TI - Degradation of oleic acid in anaerobic filters: the effect of inoculum acclimatization and biomass recirculation. AB - The degradation of oleic acid in anaerobic filters was studied and the effect of an acclimated inoculum and biomass recirculation was evaluated. Three anaerobic filters (R1, R2, and R3) were operated in parallel. The anaerobic filters R1 and R2 were inoculated with nonacclimated biomass, whereas the anaerobic filter R3 was inoculated with acclimated biomass. In the anaerobic filters R2 and R3, biomass settling and recirculation were applied. The use of an acclimated inoculum and biomass recirculation (R3) was beneficial in terms of removal efficiency, which was 4 to 8% higher than in the anaerobic filters R1 and R2 when oleate was the sole carbon source fed to the reactors at an applied organic load of 12.5 kg of chemical oxygen demand (COD)/m3 x d, even with an oleate to calcium and magnesium ion molar concentration ratio of 6.8. Biomass recirculation significantly reduced the biomass washout and the toxic effect on the acetogenic and methanogenic populations. The use of an acclimated inoculum was beneficial in terms of methane yield, which was 50% greater than that observed for the reactors inoculated with nonacclimated inoculum for the highest applied organic loading rate (12.5 kg COD/m3 x d). At the end of the operation, the biomass was encapsulated by a whitish matter, which was well detected by microscopic examination. When this sludge was incubated in batch vials at 37 degrees C where no substrate was added, methane production from the adsorbed organic matter was evidenced, attaining a maximum value (at standard temperature and pressure) of 39.7 mL/g volatile solids x d for the biomass taken from R1. With stirring (150 r/min), the methane production rate was 13.8 times higher than under static conditions. When oleate was added to this sludge, methane production was delayed, suggesting that adsorbed matter can be an intermediate of oleate degradation such as stearic, palmitic, myristic, or other saturated acids. PMID- 11765999 TI - Upflow anaerobic sludge blanket treatment of starch wastewater containing cyanide. AB - Treatment of tapioca starch wastewater containing cyanide using an upflow anaerobic sludge blanket (UASB) process was investigated. Sludge from an anaerobic lagoon treating tapioca starch wastewater was used as seed. Performance of the UASB reactor with influent cyanide concentrations up to 25 mg/L was assessed. The inhibitory effects of cyanide were temporary and reversible. The process required longer recovery period for higher cyanide dosage. For 25 mg/L of cyanide concentration in the feed, the reactor required 15 days for complete recovery. Process performance was sensitive to operating parameters such as upflow velocity, cyanide loading rate, and chemical oxygen demand (COD) loading rate. A maximum cyanide loading rate of 0.38 kg/m3 x d was achieved in the process at a COD loading rate of 50 kg COD/m3 x d. Experiments with tapioca starch wastewater containing up to 10 mg/L of cyanide yielded satisfactory cyanide removal of approximately 93 to 98% and gas productivity of 7.5 m3/m3 x d with a COD loading rate of 30 to 40 kg COD/m3 x d. PMID- 11766000 TI - Seeding effect on cocomposting wastewater biosolids with coal fly ash. AB - The seeding effect on fly ash-amended biosolids composting was evaluated by inoculating a mixture of ash and biosolids with seeding materials before composting. These inocula included thermophilic bacteria (Bacillus. brevis, B. coagulans, and B. licheniformis) isolated from the ash-biosolids compost, a commercial decomposter, and recycled biosolids compost. Although the addition of these microbial additives to the ash-biosolids compost improved the population of thermophilic bacteria at the early stage of composting, the improvement was negligible after 4 days of composting. Inoculation with isolated bacterial culture, milk powder, or the decomposter, only, did not effectively improve the decomposition of organic matter compared with those receiving inoculation of both microbial additives and milk powder together. The isolated Bacillus species was as efficient as the commercial decomposter in accelerating the decomposition rate during ash-amended biosolids composting as indicated by the high amounts of carbon dioxide evolved and cumulative weight loss. Ash-biosolids compost inoculated with 15% (dry weight basis) of recycled compost showed a comparable decomposition activity to those inoculated with bacterial culture and the commercial decomposter with milk powder. Taking into consideration the lower operating cost and acceptable decomposition efficiency, recycled biosolids compost seemed to be a promising additive to ash-amended biosolids compost to improve composting efficiency. PMID- 11766001 TI - Genetic background of diabetic and nondiabetic sibs in young Bangladeshis. AB - The prevalence of diabetes mellitus in the young is higher in Bangladesh like other Asian developing nations. Albeit, undernutrition has been shown to be associated with diabetes in the young, not all such individuals are diabetic. Diabetes Mellitus is a multigenic disease. In IDDM, DR3/4 heterozygotes were shown to have a greatly increased risk of developing the disease, suggesting the concept of genetic factor(s) being involved in the development of diabetes. Therefore, this study was undertaken to determine the distribution of HLA class II alleles (DRB) and to identify the HLA associated risk for developing diabetes mellitus in the young Bangladeshis. A total of fifty individuals were investigated. Half of them (n=25) were diabetic patients, registered in BIRDEM and half the participants were their non-diabetic sibs. A genomic DNA PCR and Enzyme Linked Probe Hybridization Assay (ELPHA, Bio-test, Germany) was used to determine HLA class II alleles (DRB1, DRB 3, 4, 5) by in vitro amplification of DRB gene. Among all the sero-equivalent antigens found in the study subjects, the prevalence of DR15 (DR2) was overrepresented, both in the diabetic subjects and in their non-diabetic sibs. Moreover, compared with the non-diabetic group the diabetic patients showed higher frequency of DR15 alleles (39 and 25%) though the difference was not significant (chisq. 1.7, p>0.05). Next to DR15, DR4 was the most prevalent HLA-DRB gene found in the study population. Interestingly, the frequency of DR4 was higher in the diabetic than in the non-diabetic group (20 vs. 14%). The study showed that the DR15 and DR4 were the most prevalent in the study population. Moreover, DR7 though not very significant, was higher in non diabetic compared to their diabetic sibs. Comparison between the diabetic and non diabetic sibs could have been interesting and significant but we could not confirm our findings, possibly, due to small sample size. A study in a larger paired sample of unrelated population is also needed to substantiate our findings, and also to prove the susceptibility or resistant haplotype in the young diabetic subjects. PMID- 11766002 TI - Seroprevalence of rubella antibodies among antenatal population attending a tertiary level hospital in Dhaka City. AB - This study was performed to identify the seroprevalence of rubella IgG among the antenatal population attending a tertiary level hospital in Bangladesh. Sera from 609 pregnant women were tested for rubella IgG antibody using enzyme linked immunosorbent assay (ELISA) technique. Of the 609 pregnant women, 85.9% were seropositive and 14.1% were seronegative. The prevalence of the antibody was 80% between 15 and 20 years of age. This figure gradually increased with age until it peaked at 90.2% in the age group of 31-36 years. Then the seropositivity decreased to 81.3% in the age group of >36 years. No statistically significant difference of seroprevalence was found among housewives vs service-holders. This small preliminary study indicates that, like many other countries rubella is endemic in Bangladesh. The results of this study indicate the need for more detailed epidemiological studies to be used as the basis for a national immunization programme. PMID- 11766003 TI - Pulmonary metastases in recurrent cervical carcinoma--a report of four cases and review of issues specific to the treatment. AB - Postoperative extrapelvic distant metastasis of cervical carcinomas are usually difficult to diagnose and to treat, and their prognoses are rather poor. We present 4 cases of recurrent cervical carcinomas metastatic to the lung. The prognostic factors and effective therapeutic modalities were elucidated. In addition, the literature on postoperative pulmonary metastasis of uterine cervical carcinomas was reviewed and discussed. PMID- 11766004 TI - Detection of Mycobacterium leprae by Polymerase Chain Reaction. AB - The improved procedure based on Polymerase Chain Reaction (PCR) for detection of M. leprae has been developed. The sensitivity and specificity of this method were tested using different concentration of genomic DNA of M. leprae Thai 53 and genomic DNAs from mycobacterial species and related microorganisms respectively. Application of this method to biopsy samples obtained from Bangladesh was conducted and detected M. leprae DNA in 7 of the 10 clinical specimens. Acid fast bacilli were not detected in four of the seven positive cases under the microscopic observation. It was concluded that this method was sensitive and specific for detection of M. leprae in clinical specimens and also simple to detect in only one step of PCR. PMID- 11766005 TI - Incidence of malignancy in microscopic haematuria: a study of 100 cases. AB - During June, 1998 to April, 2000, one hundred cases of microscopic haematuria were evaluated. All were symptomatic patient with age ranging from 24-68 years. 70 (70%) cases were male and 30 (30%) cases were female. Commonest presentation was dysurea 70 (70%). Urinary stone disease was the commonest cause found to be present in 25 (25%) cases. Malignant lesion was found in 16 (16%) cases of which bladder tumour was found in 10 (10%) cases. PMID- 11766006 TI - SPECT in the field of Neurology. PMID- 11766007 TI - Re: Shaken baby syndrome and hypothermia. PMID- 11766008 TI - The credibility of recovered memory testimony: exploring the effects of alleged victim and perpetrator gender. AB - OBJECTIVE: The purpose was to explore the effects of victim/complainant and perpetrator/defendant gender on the impact of recovered memory testimony in criminal sexual abuse trials. METHOD: A jury simulation methodology was used. Two hundred forty-six participants read a summary of a sexual abuse trial in which the following three variables were manipulated: the complainant's gender, the defendant's gender, and whether the complainant's memory of the alleged abuse had been "recovered" or remembered all along. Participants reached a verdict and rated the culpability and credibility of the parties. RESULTS: Compared to a case where the memory of the abuse had always been remembered, recovered memory testimony led to lower perceptions of the defendant's culpability and higher perceptions of the defendant's credibility. In addition, the complainant with recovered memory was viewed as less credible and less likely to be telling the truth. These effects of testimony type (i.e., recovered vs. remembered) were qualified by an interaction with complainant and defendant gender, such that testimony type exerted an effect in cases of alleged heterosexual but not homosexual abuse. CONCLUSION: The results suggest that mock jurors' judgments in sexual abuse cases reflect their stereotypes about sexual abuse and expectations regarding the relative likelihood of repression in various circumstances. PMID- 11766009 TI - The effect of being a victim or witness of family violence on the retrieval of autobiographical memories. AB - OBJECTIVE: This study was designed to determine whether greater reliance on general memory retrieval in children was related to depression, and whether family violence affected the specificity of children's memory retrieval. METHOD: We compared children who had experienced some form of family violence with children who had never experienced any form of family violence, based on their responses to questions concerning child-parent and interparental disagreements. RESULTS: As expected, there was a positive correlation between the extent of "generic-categoric" memory retrieval and depression level. There was no evidence, however, that autobiographical memory was affected by family violence. CONCLUSIONS: This study is the first to report significant associations between depression and autobiographical memory style in children. The results suggest that the effect of family violence on children's memory retrieval may be mediated by depression. PMID- 11766010 TI - Intergenerational transmission of abuse: a two-generational prospective study of an at-risk sample. AB - OBJECTIVE: A model was examined in which the association between a parent's history of abuse and the parent's own abusive behavior toward his or her children was hypothesized to be mediated by parental psychopathology, early childbearing, and consistency of discipline. Additionally, the effect of severity of abuse on the likelihood of becoming abusive was examined. METHOD: Participants were 109 parents (G1) and their male children (G2) who were involved in a longitudinal study. The G1 parents reported on their own experiences of abuse when they were children. Ten years later, the G2 youths reported on the G1 parents' abusive behavior toward them. A number of other factors, including parental socioeconomic status (SES), antisocial behavior, depression and Post-traumatic Stress Disorder (PTSD), consistency of discipline, and the perceived early difficulty of the G2 children were measured. RESULTS: As reported by their own children, parents who reported having been abused in childhood were significantly more likely to engage in abusive behaviors toward the next generation. Findings indicated that abuse experienced by the parents, as well as consistency of discipline and depression plus PTSD, were predictive of parental abuse of the child. Contrary to hypotheses, the effects were not fully mediated. However, there were significant interactions between parental history of abuse and consistency of discipline, as well as abuse history and depression and PTSD. Parents who had experienced multiple acts of abuse and at least one physical impact were more likely to become abusive than were the other parents. CONCLUSIONS: The implications of these findings for preventive interventions are discussed. PMID- 11766011 TI - Coping resources of maltreated children in the family: a salutogenic approach. AB - OBJECTIVE: Most research in child maltreatment within family focuses mainly on the pathological damage caused to the battered child. This study, based on a salutogenic approach, focuses on the resources that may help maltreated children to cope with their state and stay well. METHOD: Resilience was measured by two variables: perceived competence and psychological distress. The moderating or buffering variables that may contribute to better coping were: sense of family coherence, psychological sense of school membership, and social support. Two hundred and twenty-six 8th graders answered an anonymous self-report inventory. Based on the students' answers, they were divided into two groups: those who reported that they had been maltreated (MC) (n = 81) and those who did not (NMC) (n = 145). RESULTS: The study revealed a significantly high percentage of adolescents (35.6%) who reported having been maltreated within their families. A significant difference was found between the MC and the NMC in levels of perceived competence (higher for the NMC) and psychological distress (higher for the MC group). The moderating variables were found to have a differential effect on the dependent variables within the two groups. Sense of family coherence was found to be the main contributor to variance explanation of perceived competence among the MC, while sense of school membership had the main effect among NMC. CONCLUSIONS: The findings support a salutogenic approach in studying maltreated children. Implications on the possible detection of maltreated children in the community and on their coping resources that may contribute to resilience are discussed. PMID- 11766012 TI - The Child Abuse Potential Inventory and pregnancy outcome in expectant adolescent mothers. AB - OBJECTIVE: The study explores the prenatal Child Abuse Potential (pCAP) scores derived from the Child Abuse Potential Inventory administered to expectant adolescent mothers. The aim of the study was to assess the association of the pCAP scores with maternal negative prenatal behaviors, and evaluate the contribution of the pCAP scores to neonatal morbidity. METHOD: The pCAP scores, demographic data, and self-report on prenatal behaviors were obtained during the second half of the pregnancy in a sample of 45 poor single adolescent mothers. A pediatrician blind to the prenatal data reviewed the neonatal records to assess neonatal morbidity. Maternal prenatal records were reviewed for obstetric risk assessment by an obstetrician who was blind to the rest of the data. The relations among the pCAP scores, prenatal behaviors, and neonatal morbidity were analyzed. RESULTS: In the prenatal period, the pCAP scores were positively correlated with self-reported prenatal smoking and substance use. The multiple linear regression analysis showed that the pCAP scores significantly contributed to neonatal morbidity independently of obstetric risk factors. CONCLUSIONS: The Child Abuse Potential scores obtained during pregnancy in poor single adolescent mothers reflect domains of maternal functioning that are associated with negative prenatal behaviors and appear to be important for predicting neonatal morbidity. Further studies are warranted to validate the prenatal use of the Child Abuse Potential Inventory. PMID- 11766013 TI - Communication between courts and expert witnesses in legal proceedings concerning child sexual abuse in Sweden: a case review. AB - OBJECTIVE: The objective was to explore the communication between courts and expert witnesses in legal proceedings concerning child sexual abuse in Sweden. METHOD: A cross professional research team performed a qualitative text analysis of files covering 20 court cases (court report and expert witness statement) from 4 different years (1985, 1989, 1992, and 1997). RESULTS: Expert witnesses applied a wide variety of assessment procedures. Several patterns of communicative difficulties were identified, categorized as "mismatch," "misunderstanding," "misuse," and "missing pieces." Experts and courts sometimes used similar words (e.g., "credibility") but seemed to apply different meanings to them, indicating a lack of a mutual conceptual framework. CONCLUSIONS: The combination of brief expert assignments and diverse assessment procedures turned out to be a specific risk factor for communicative impairment. Alternate strategies for improved communication are discussed. PMID- 11766014 TI - The nature and frequency of reported cases of teacher perpetrated child sexual abuse in rural primary schools in Zimbabwe. AB - OBJECTIVE: The main purpose of this study was to investigate the nature and magnitude of reported cases of teacher perpetrated child sexual abuse of rural primary school pupils in Zimbabwe. The study also determined the distribution of reported cases of child sexual abuse according to the characteristics of victims and perpetrators. METHOD: This is a retrospective case series study of reported cases of child sexual abuse drawn from six randomly selected educational jurisdictions. The study covered an 8-year period (1990-1997) and used a study sample of 110 nonclinical case files of teacher perpetrators. Descriptive statistics were used to analyze the findings. RESULTS: Gender-wise, 108 (98%) of the victims were girls, while all perpetrators were male teachers. Penetrative sex was the most prevalent (70%) type of sexual abuse. Meanwhile, the modal age for sexual abuse in the study sample was 12 years, which represents 46% of reported cases, while the most vulnerable age group comprised pubertal (11-13 years) children, who accounted for 69% of all sexual abuse cases. On the one hand, beginning teachers (0-5 years), who comprised 63% of the study sample, were most at risk of sexually abusing school children. Finally, 78% of 32 cases handled by the courts resulted in convictions, while 83% of all teacher perpetrators were dismissed from the teaching service. CONCLUSION: The results of the study clearly indicate that the problem of teacher perpetrated child sexual abuse is not uncommon among rural primary schools in Zimbabwe. The study has also shown that the perpetrators of child sexual abuse in rural primary schools are generally male teachers; a majority of them are young and inexperienced. Finally, this study showed that penetrative sex was the most prevalent form of abuse (70%), perpetrated on predominantly female victims (98%), and that all perpetrator teachers were males, and may clearly reflect Zimbabwe's highly patriarchal society. PMID- 11766015 TI - Reaction to videocolposcopy in the assessment of child sexual abuse. AB - OBJECTIVE: The purpose of this study was to clinically assess children's reactions to videocolposcopy with real-time observation of magnified anogenital images (VCO), and to evaluate whether these reactions are affected by patient or other characteristics such as response to preparation, disclosure of child sexual abuse (CSA), or examination findings. METHOD: Consecutive cases of children ages less than 18 years referred to a children's hospital clinic for nonemergent evaluation of suspected CSA during 1997 through 1999 were studied. We noted the child's response with clinical observation before and after videocolposcopy, and used the Genital Examination Distress Scale (GEDS) after evaluation. We compared these responses to patient gender, age, ethnicity, pubertal status, disclosure of child sexual abuse (CSA), and physical examination findings using univariate and regression analyses. RESULTS: Two hundred twenty-seven children (mean age 7.2 years, range 0-17) underwent videocolposcopy, of whom 55.1% disclosed sexual abuse and 17.2% had a positive examination. More than 80% were female, prepubertal, and non-Hispanic White. Most (85%) watched their examination on the monitor and were either cooperative or enthusiastic before and after videocolposcopy. Fewer very young children (ages 0-3 years) or female adolescents (13-17 years) watched the monitor. Summed GEDS scores were strongly correlated with observed responses after the procedure (p = .01), and children with CSA disclosure were three times more likely to watch the monitor and five times more likely than those without disclosure to have improved comfort. Other patient characteristics were not significantly associated with patient reaction to VCO. CONCLUSIONS: Most children are interested in watching their anogenital examination using magnified real-time images obtained during videocolposcopy and tolerate the procedure well. The GEDS is highly correlated with subjective clinical observation. While some children may particularly benefit from participating in their examination by using VCO, long-term effects of the evaluation and any relationship of a child's reaction to videocolposcopy with their history of sexual victimization remain to be established. PMID- 11766016 TI - Risk of prion transmission with the use of xenografts and allografts in surgery. PMID- 11766017 TI - Subperiosteal abscess of the orbit: older children and adults require aggressive treatment. PMID- 11766018 TI - Intracranial abscess as a complication of subperiosteal abscess of the orbit. AB - PURPOSE: To describe the potential complication of intracranial abscess in the setting of orbital abscess. METHODS: We retrospectively reviewed case reports and the literature. Three patients were found to have pansinusitis progressing to subperiosteal abscess of the orbit and subsequent intracranial abscess. RESULTS: Three patients, ages 14, 26, and 57 years, with concurrent pansinusitis, subperiosteal abscess of the orbit, and intracranial abscess were treated with intravenous antibiotics and surgical drainage of the orbital abscess and sinuses. Two of the three patients required drainage of the intracranial abscess. CONCLUSIONS: Although rare, intracranial abscess is a life-threatening complication of orbital abscess. It requires aggressive intervention by a multidisciplinary team. PMID- 11766019 TI - Depressor supercilii muscle: anatomy, histology, and cosmetic implications. AB - PURPOSE: To describe the gross and microscopic anatomy of the depressor supercilii muscle and to discuss its cosmetic implications. METHODS: The depressor supercilii muscle was studied in detail with the use of gross anatomic dissections carried out on eight sides of four fresh cadaver heads and ten sides of five preserved cadaver heads. Histological analysis was performed on parasagittal sections of one side of a preserved cadaver head. Measurements were taken on cadaver specimens to determine the insertion point of the depressor supercilii muscle on the undersurface of the skin. RESULTS: The depressor supercilii muscle is distinct from the corrugator supercilii muscle and the medial head of the orbital portion of the orbicularis oculi muscle. The depressor supercilii muscle was noted to be superior in orientation and redder in color than the orbicularis oculi muscle. The depressor supercilii muscle arose from the frontal process of the maxilla approximately 1 cm above the medial canthal tendon and appeared to originate from two distinct heads in most specimens, a novel finding. In specimens containing two heads of the depressor supercilii muscle, the angular vessels passed between the two muscle heads. In specimens containing one muscle head, the angular vessels were found anterior to the muscle. The insertion of the depressor supercilii muscle in the dermis lay approximately 13 to 14 mm superior to the medial canthal tendon. CONCLUSIONS: The origin, insertion, and anatomy of the depressor supercilii muscle help it to act as a depressor of the eyebrow. Histologically, the depressor supercilii muscle arises distinctly from bone and has a unique insertion. The depressor supercilii muscle appears to be distinct from the corrugator supercilii and the orbicularis oculi muscles. PMID- 11766020 TI - Marcus Gunn jaw-winking phenomenon: a new supplemental test in the preoperative evaluation. AB - PURPOSE: To introduce a new method for the evaluation of Marcus Gunn jaw-winking ptosis that more precisely defines the severity of blepharoptosis. METHODS: A retrospective review of 16 consecutive patients with Marcus Gunn jaw-winking ptosis presenting to our institution between 1993 to 1999 was performed. The position of the affected eyelid was observed after applying a technique of jaw immobilization and disruption of fusion with temporary occlusion of the ipsilateral side. RESULTS: In patients presenting with mild to moderate Marcus Gunn jaw-winking, the majority (62.5%) demonstrated a positive test, uncovering complete or near complete ptosis. Test results were partially positive in 3 patients (18.8%) with increased but not complete ptosis and negative in 3 patients (18.8%) with no change in eyelid position. CONCLUSIONS: Blepharoptosis associated with Marcus Gunn jaw-winking phenomenon is often more severe than found by conventional clinical evaluation. This finding may explain the frequent undercorrection and unpredictable results following levator resection. In patients exhibiting a positive jaw-winking ptosis test, disappointing outcomes with levator resection may be avoided by instead proceeding with a frontalis suspension with levator disinsertion as recommended for ptosis with severe jaw winking. PMID- 11766021 TI - Mersilene mesh as an alternative to autogenous fascia lata in brow suspension. AB - PURPOSE: To evaluate the outcome and complications of brow suspension surgery for ptosis repair performed with Mersilene mesh as the suspensory material. METHODS: A retrospective review was undertaken of all patients undergoing Mersilene mesh brow suspension surgery during a 9-year period. All patients had undergone the same surgical procedure performed by the same surgeon. Preoperative and postoperative palpebral aperture heights were recorded, and the results were analyzed to provide a mean change in palpebral aperture height. The case records of patients with a poor response to surgery were examined carefully, and possible risk factors for a poor outcome were identified. RESULTS: The mean (95% confidence interval) increase in palpebral aperture height was 1.8 mm (1.2-2.4 mm). Factors associated with a poorer outcome were previous ptosis surgery and Marcus Gunn jaw-winking syndrome. CONCLUSIONS: Mersilene mesh has advantages over other materials for use as a suspensory material in brow suspension surgery, and is associated with a good outcome and low complication rate. PMID- 11766022 TI - Comparison of palpebral fissure obliquity in three different racial groups. AB - PURPOSE: To compare the obliquity of the palpebral fissures of three different racial populations. METHODS: Prospective observational study. Frontal views of the palpebral fissures of three different groups of subjects (Brazilian whites, Brazilian Japanese, and Brazilian Indians from the Upper Rio Negro Basin of the Amazonas State) were acquired with a photographic camera and transferred to a Macintosh computer. Using the National Institutes of Health Image software (NIH Image), the angle formed by the inner and the outer canthi was measured for all images. RESULTS: The mean fissure angle of the Japanese (9.39 degrees) was not statistically different from the mean angle of the Indians (9.64 degrees). On the other hand, both were significantly greater than the mean angle of the whites (4.60 degrees). CONCLUSIONS: Marked fissure obliquity is found more frequently among Asians than among whites. PMID- 11766023 TI - The arm as a skin graft donor site in eyelid reconstruction. AB - PURPOSE: To report the technique, success, and complications of using the arm as a donor site for full-thickness skin grafts used in eyelid and facial reconstruction. METHODS: The charts of 42 patients were reviewed. The arm was used as a donor site for harvesting full-thickness skin grafts in 52 procedures of eyelid or facial reconstruction. RESULTS: The size of skin grafts varied from 4.0 cm2 to 59.5 cm2. There were few recipient site complications: partial necrosis (n=2), severe contraction (n=2), and hair growth (n=4). Donor site complications included wound dehiscence (n=2) and hypertrophic scarring (n=2). CONCLUSIONS: The arm is an acceptable donor site for harvesting full-thickness skin grafts for use in eyelid and facial reconstruction when either traditional donor sites are unavailable or a large amount of skin is needed. PMID- 11766024 TI - Exposure rates of wrapped and unwrapped orbital implants following enucleation. AB - PURPOSE: To compare the complication rate of porous polyethylene orbital motility implants with solid acrylic implants following enucleation and identify possible risk factors. METHODS: The authors retrospectively reviewed the charts of a total of 117 consecutive enucleations performed at the University of Illinois at Chicago between March 28, 1994, and May 28, 1999. Data obtained included patient demographics, surgical indication, implant type, attending surgeon, surgical technique, and any reported complications. The primary outcome was presence or absence of implant exposure at the final recorded visit. RESULTS: Of the 117 identified cases, 29 were eliminated due to insufficient follow-up data. Of the 88 remaining cases, 48 patients received porous implants and 40 received solid acrylic implants. Implant exposure developed in four cases. All exposures occurred in unwrapped porous polyethylene implants (n=2) or porous polyethylene implants wrapped in absorbable material (n=2). All exposures occurred in patients younger than 18 years of age, and 75% occurred early after trauma-associated enucleation surgery. CONCLUSIONS: The exposure rate of porous polyethylene implants in this study (9%) was found to be comparable to published rates for hydroxyapatite implants. There were no exposures of unwrapped solid acrylic spheres. Unwrapped porous implants in pediatric patients or following trauma related enucleation may represent an increased risk for postoperative implant exposure. Absorbable wrapping of porous implants may carry the same risk for exposure as no wrapping. Porous implants wrapped in durable material appear to be as safe as solid acrylic spheres. PMID- 11766025 TI - Sentinel lymph node biopsy for conjunctival melanoma. AB - OBJECTIVE: To investigate the feasibility and safety of preoperative lymphoscintigraphy and sentinel lymph node (SLN) biopsy for conjunctival melanoma. METHODS: A 49-year-old man with a biopsy-proven malignant melanoma of the conjunctiva (caruncle) underwent preoperative lymphoscintigraphy and SLN biopsy using a technique in which both isosulfan blue dye and technetium Tc 99 m sulfur colloid were injected in the subconjunctival space around the primary lesion. The conjunctival melanoma was excised just before identification and removal of the SLNs. The SLNs were excised along with concomitant dissection of their associated lymph node basins. The SLNs were evaluated histologically using serial sectioning and immunohistochemical staining with antisera against the S 100 protein and the melanoma antigen HMB-45. RESULTS: Three SLNs were identified in the left submandibular and the left upper and middle jugular lymph node basins during the preoperative lymphoscintigraphy. The same three SLNs were successfully identified in the operating room. The SLNs were histologically negative, and the immunohistochemical staining against S-100 and HMB-45 was also negative. We did not observe any immediate adverse effects on the globe or the periocular structures from lymphatic mapping and SLN biopsy. By 24 hours after injection of blue dye, only a faint trace of blue was visible on the ocular surface. CONCLUSIONS: Preoperative lymphoscintigraphy and SLN biopsy can be performed safely in patients with conjunctival melanoma. A larger study is planned to determine the sensitivity of this technique for the detection of occult regional nodal disease in patients with conjunctival melanoma. PMID- 11766026 TI - Congenital orbital cyst detected and monitored by prenatal ultrasonography. AB - PURPOSE: High-resolution prenatal ultrasound can allow for early detection and monitoring of many fetal anomalies, including those involving the globe and orbit. We describe a case of a congenital orbital cyst detected and monitored by prenatal transvaginal ultrasonography. METHODS: After detection of a congenital orbital cyst, serial transvaginal ultrasound examinations were performed through the remainder of the pregnancy to monitor the growth and development of the fetus and the orbital cyst. RESULTS: A large retrobulbar orbital cyst causing extreme proptosis was detected at 23 weeks of gestation and monitored through the remainder of the pregnancy. Lack of growth, benign behavior, and appropriate interval fetal growth without destruction of adjacent structures was noted. After birth, early surgical intervention allowed for complete surgical excision of the cyst without the need for enucleation or exenteration. Fifteen months after excision, the patient wore a scleral shell and had a good cosmetic appearance with good ocular motility. CONCLUSIONS: Prenatal ultrasound may allow for early detection of orbital masses. To our knowledge, this report describes the first case of a congenital orbital cyst detected and monitored by prenatal ultrasonography. PMID- 11766027 TI - The use of a computer-assisted image-guided system (InstaTrak) in orbital surgery. AB - PURPOSE: To assess the usefulness of a computer-assisted image-guided system (CAIGS) as an intraoperative anatomical guide in performing orbital surgery. METHODS: Noncomparative interventional case series of 30 consecutive orbital procedures performed by one surgeon (J.G.C.) using the CAIGS (InstaTrak) for intraoperative anatomical guidance. RESULTS: The series consisted of 8 cases of orbital decompression, 8 cases of orbital fracture, 11 cases of tumor excision, 2 cases of orbital reconstruction for severe enophthalmos, and 1 case of drainage of an orbital abscess. The CAIGS (InstaTrak) was useful in providing adjunctive intraoperative guidance in all 30 orbital cases. CONCLUSION: The CAIGS (InstaTrak) system is a useful adjunctive tool in providing intraoperative anatomic guidance in a consecutive series of varied orbital operations. PMID- 11766028 TI - Aspergillus niger infection of exenterated orbit. AB - PURPOSE: To present two immunocompetent patients with Aspergillus niger infection of the exenterated orbit. METHODS: Case reports. RESULTS: The patients were treated with oral itraconazole and socket irrigation with amphotericin B. The sockets cleared completely; no growth was observed on reculturing. CONCLUSIONS: A niger infection of an exenterated socket can be effectively treated with oral itraconazole and topical amphotericin B in immunocompetent patients. PMID- 11766029 TI - Acinic cell carcinoma of the lacrimal gland with intracranial extension: a case report. AB - PURPOSE: To describe a patient with acinic cell carcinoma of the lacrimal gland presenting with atypical manifestations including erosion of the orbital roof and intracranial extension. We compare his clinical manifestations with two previously reported cases. METHODS: Case report. RESULTS: A 51-year-old man presented with a firm, tender, palpable mass in the superior temporal portion of his right orbit. CT scan demonstrated a large homogeneously enhancing mass displacing the globe inferiorly and eroding the roof of the orbit. MRI of the orbit showed intracranial extension of tumor. Biopsy revealed an acinic cell carcinoma of the lacrimal gland. CONCLUSIONS: Acinic cell carcinoma is a rare neoplasm occurring primarily in the major and minor salivary glands. PMID- 11766030 TI - Intracranial paraganglioma (glomus tumor) with orbital extension. AB - PURPOSE: To describe the clinical features of an intracranial glomus tumor with orbital extension. METHODS: Case report. RESULTS: A 15-year-old girl was examined for a large, vascular intracranial mass extending into the orbit. Attempted orbital biopsy was aborted for fear of uncontrollable hemorrhage. Tumor embolization and partial resection was performed. Histology was consistent with paraganglioma (glomus tumor). CONCLUSION: The orbital surgeon should include glomus tumor in the differential diagnosis of vascular orbital lesions. Their vascularity and hemorrhagic potential should be considered when approaching these lesions surgically. PMID- 11766031 TI - Respiratory choristomatous cysts in the temporal orbit. AB - PURPOSE: To describe the clinical and histopathological findings in two patients with cystic lesions located in the temporal orbit. METHODS: Case reports. RESULTS: Cystic lesions excised from the temporal orbit of two patients were found to be lined with ciliated pseudostratified epithelium, consistent with a choristoma composed of tissue derived from the respiratory system. A review of the literature suggests that this is an uncommon cause of a cystic orbital mass. CONCLUSIONS: Respiratory choristomatous cysts should be considered in the differential diagnosis of cystic lesions of the temporal orbit. PMID- 11766032 TI - Complications associated with silicone intracanalicular plugs. AB - PURPOSE: To assess American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) member physicians' experiences with complications associated with silicone intracanalicular plugs and publicize risks associated with this device. METHODS: Two case reports are presented. A survey was sent to 420 ASOPRS member physicians, questioning them on their experiences with complications associated with silicone intracanalicular plugs. RESULTS: We present two case reports of complications associated with migration of intracanalicular plugs. In the first case, a 41-year-old man underwent serial insertion of seven intracanalicular plugs in one eye over several years, he had a 3-month relapsing course of Nocardia asteroides canaliculitis, dacryocystitis, and cellulitis requiring systemic antibiotics and multiple surgeries. In the second case, a 72 year-old woman had acute dacryocystitis, eventually necessitating dacryocystorhinostomy; at surgery, an intracanalicular plug was discovered in the lacrimal sac. One hundred fifty-nine usable survey responses were obtained. Sixty one percent of respondents reported various complications including tearing, canaliculitis, and dacryocystitis. Fifty-one percent of respondents performed surgery to treat complications associated with silicone intracanalicular plugs. CONCLUSIONS: Silicone intracanalicular plugs may be difficult to remove and may be associated with significant lacrimal complications. PMID- 11766033 TI - Squamous cell carcinoma with perineural spread. PMID- 11766034 TI - A GIS methodology for the real-time assessment of micro-pollutant concentration in river: application to the Lake Biwa basin in Japan. AB - For integrated water management in the future, the real-time assessment of toxic micro-pollutant concentrations in rivers is required, since these pollutants cause various irreversible and adverse effects in the environment. In this research, a GIS (Geographical Information System) methodology using EMC (Event Mean Concentration) was established for estimating the SS (Suspended Solids) concentration that strongly sorbs organic micro-pollutants. The GIS was applied to the Lake Biwa basin in Japan. On non-point sources, it was found that in some rivers the upstream SS concentrations could become greater than those in downstream, which suggested thatthe environmental improvement measures in downstream waters arenot always appropriate. For effective use of this GIS methodology, the improvement of the GIS model is necessary and up-to-date data should be kept in constant readiness, which leads to an ideal integrated water quantity and quality management in the future. PMID- 11766035 TI - Biological treatment of oil field wastewater in a sequencing batch reactor. AB - This work reports the results of experiments carried out in a sequencing batch reactor (SBR) operated under 24 hour cycles, treating an effluent containing a mixture of oil field wastewater and sewage, in different percentages. The removal of phenols, ammonium and COD was monitored in several experimental runs, varying the dilution degree of the oilfield wastewater (10 to 45% v/v). The volatile suspended solids (VSS) content in the reactor was also monitored and the protein (PTN) and polysaccharide (PS) contents of the suspended biomass were determined. The removal of ammonium and phenols did not vary significantly in the experimental runs, attaining average values of 95% and 65%, respectively. COD removal efficiencies in the range of 30 to 50% were attained in the experiments carried out with dilution percentages of 45 and 35% (v/v) respectively. An experiment carried out with a lower proportion of produced water (15% v/v), keeping the salinity level corresponding to a higher proportion of industrial effluent (45% v/v), led to an improvement in the COD removal, indicating that the recalcitrance of the organic compounds found in the effluent is the main cause ofthe moderate COD removal efficiencies attained in the SBR system. With regard to the composition of the microbial flocs, no significant variation was observed in the PS/PTN, PS/VSS and PTN/VSS ratios when the effluent composition changed (increased salinity and levels of organic material). PMID- 11766036 TI - Kinetics of oxidation of odorous sulfur compounds in aqueous alkaline solution with H2O2. AB - Sulfur species oxidation is a crucial issue wastewater treatment. The production of sulfur compounds like H2S,CH3SH, C2H5SH, disulfides and dimethyle sulfide generates odorous nuisances for the neighborhood. The oxidation of these species by H2O2 in alkaline solution has been investigated. The results showed that thiols CH3SH and C2H5SH react with H202 only in their dissociated form RS- with rate constants respectively k = 8.81 +/- 0.48 M-1s-1 and 8.37 +/- 0.63 M-1.s-1. Mercaptans oxidation produces 100 % of dimethyldisulfide or diethyldisulfide. The oxidation of disulfides shows a difference of reactivity between H2O2 and HO2- towards sulfur species. Increasing the pH accelerates significantly the reactions in the case of CH3SSCH3. The oxidation rate can be described as: r = k[RSSR][H2O2][RSSR][H2O2] + k[RSSR][HO2-] [RSSR][HO2-] with k[RSSR][H2O2] = 1.2 x 10(-4) +/- 0.2 x 10(-4) M-1s-1 and k[RSSR][HO2-] = 3.4 x 10(-4) +/- 0.6 x 10(-4) M-1.s-1 for CH3SSCH3. Dimethyl sulfide presents a reactivity different from disulfides. The oxidation rate can also be described as: r = k[CH3SCH3][H2O21][CH3SCH3][H2O2] + k[CH3SCH3][HO-] [CH3SCH3][HO2-], however, oxidation rate decreases with pH increase. k[CH3SCH3][H2O2] = 12.8 x 10(-3) +/- 0.96 x 10(-3) M-1.s-1 and k[CH3SCH3][HO2-] = 4 x 10(-3) +/- 0.3 x 10(-3) M-1.s-1. PMID- 11766037 TI - Heavy metal and nutrient concentration in soil and plants growing on a metalliferous chromite minespoil. AB - Metal contamination in soil and plant samples from a chromite mine and its adjoining regions was determined. The metal concentration varied in stem, leaf and root of different tree species. In the case of shrubs, the highest concentration of iron (18.5 mg kg(-1) was detected in the stem of Combretum roxburghii. The concentration of aluminium varied from 1.8 - 5.3 mg kg(-1) dry weight, whereas the nickel content was found to be the highest in the stem of Calotropis gigantea. In the case of herbs, chromium concentration was highest (60.9 mg kg(-1) dry weight) in Evovulus alsenoides and the lowest (18.8 mg kg(-1) dry weight) in Andrographis paniculata. There was a significant correlation observed between chromium in soil with the root of tree species like Lagerstroemia parviflora, Madhuca longifolia, Anogeissus latifolia and Haldina cordyfolia. Nickel in soil was significantly correlated with the stem and leaf of all the tree species except Chlroxylon sweitenta. Iron in soil showed correlation with the stem and leaf of Chloroxylon sweitenia. Among the shrubs (Calotropis gigantea, Combretum roxburghii and Smilax zeylancia), chromium in soil showed a correlation with the root. Nickel in soil was positively correlated with the stem and leaf of Calotropis gigantea and Combretum roxburghii. Among the herbs, chromium in the whole plant of Evolvulus alsenoids, Solanum surattense and Phyllanthus fraternus showed significant positive correlation with soil; nickel in Solanum surattense showed significant positive correlation with soil. The positive correlation coefficient was observed between iron in the whole plant and soil on Phyllanthus virgatus, Phyllanthus fraternus and Andrographis paniculata. The above information would be useful for the establishment of a vegetation cover on the minewaste heaps. PMID- 11766038 TI - Hydraulic characteristics of an anoxic rotating biological contactor: influence of biofilm. AB - The hydraulic characteristics of an anoxic rotating biological contactor were studied under different flow rates. The experiments were carried out with the reactor clean (without biomass) and containing denitrifying biofilm (Alcaligenes denitrificans) covering the disks. Residence Time Distribution (RTD) experiments were performed by the stimulus-response technique using lithium chloride as tracer. Experiments without biomass revealed the existence of hydraulic dead volumes (around 40% for hydraulic residence time of 0.94 and 2 hours) that occur in corners, where stagnant eddies form. When in normal operation, with the disks covered by biofilm and with biogas production, these values decreased significantly. For hydraulic residence time (HRT) of 2 hours a minimum dead volume was observed, being appropriate to run the reactor under this condition, from the hydraulic viewpoint. The Dispersion number decreased with increasing HRT from 0.94 h on, for both types of experiment, without, and in the presence of biomass. For this HRT the dispersion number was maximal in both situations. A considerable diffusion of tracer into the biofilm was detected, being faster in the more hydrated biofilm, and Justifying the long tails observed in the RTD experimental curves. PMID- 11766039 TI - Effect of enforced aeration on in-vessel food waste composting. AB - A laboratory composting was conducted to determine the effect of the continuously enforced aeration on the composting performance. The mixture of dog food, excess sludge, and woodchip was used as raw composting materials. The temperature changes in the decomposition process, and pH, weight loss, ash, and extract composition from the final product after 17 days composting were investigated. The results demonstrated that flow rate of enforced aeration indeed influenced the composting performance. Composting under 0.05-0.1 1 min(-1) condition seemed better than that under 0.2-0.41 min(-1) condition. Higher flow rate of air not only cooled the composting mixture significantly, further adversely affected temperature rise, but also evaporated moisture mostly. Thermophilic composting can occur under 0.05-0.11 min(-1) air flow rate condition, while composting in cases of 0.2-0.4 l min(-1) air flow rate mainly resulted in a mesophilic process. Microbial activity was considered to be significantly inhibited at 0.4 1 min(-1) air flow rate condition based on the analyses of total organic carbon and volatile fatty acids from water extraction of composting products. PMID- 11766040 TI - Reliability and accuracy of environmental analytical data on moss samples: an interlaboratory comparison. AB - An inter-comparison exercise was performed between two laboratories on mineralised moss samples. Ten samples, together with three certified reference materials (CRM 61, CRM 62 and CRM 482) and five blanks were mineralised independently in the two laboratories and then analysed by both with different techniques (AAS, ICP-MS, and INAA). The elements analysed were: Cd, Cr, Cu, Fe, Ni, and Pb. Accuracy tests showed that, for AAS, the relative standard deviations for five repetitions of the same sample were between 0.2% for Cd and 2.9 % for Cr and that the concentration values found reference materials were withn one standard deviation from the certified values, with the exception of Cr and Cd for CRM 482. The statistical analysis was performed first with a simple linear regression and a Student t-test taking into account the possible influence of the mineralisation procedure and of the analytical technique, in order to evaluate their reliability. The results showed that more than 78% of the regressions had a correlation coefficient higher than 0.750, and that 83% of the slopes were not different from one with a level of significance of 0.01. Afterwards, the precision of the measurements were evaluated using maximum likelihood; the normalised errors showed that ICP-MS had a better performance on most of the elements analysed (with the exception of Fe) and that both the mineralisation procedures gave satisfactory results. The two laboratories were then found to produce reliable results. PMID- 11766041 TI - Biodegradation of isopropanol in a three phase fixed bed bioreactor: start up and acclimation using a previously-enriched microbial culture. AB - The aerobic biodegradation of high liquid phase concentrations of 2-propanol (IPA) by a previously enriched solvent-tolerant bacterial consortium within a 1.9 l fed-batch three phase fixed bed bioreactor was investigated. Solvent concentrations of up to 7.9 g l(-1) were investigated. Previously enriched solvent-tolerant bacterial cells were immobilised onto porous glass cylinders as a means obioprocess intensification. Bioreactor start-up and acclimation was studied anacetone concentration tracked as an indicator of IPA utilization, as the sole carbon source within a minimal salts medium (MSM). The initial batch treatment of IPA exhibited a biodegradation rate of 0.11 g l(-1) h(-1) prior to biofilm formation Biofilm growth during the second batch treatment was consistent with an increase in metabolic activity and an IPA biodegradation rate of 0.34 g l(-1), followed by a reduction of biodegradation rate to a constant value of 0.078 g l(-1) h(-1) after 650 h. A maximum acetone generation rate of 1.3 g l(-1) h(-1) was obtained during the fourth IPA addition although the maximum acetone biodegradation rate of 0.38 g l(-1) h(-1) was observed during the initial IPA addition. It is proposed that the metabolic lag resulting from switching from alcohol dehydrogenase to acetone carboxylase is a major rate-limiting step in the deep oxidation of IPA to acetone. The results demonstrate the potential of a previously enriched solvent-tolerant bacterial consortium in fixed bed bioreactor systems, for the aerobic treatment of concentrated solvent-containing wastestreams. PMID- 11766042 TI - Co-composting of pig manure with leaves. AB - The increase in the market price of sawdust makes it a less attractive bulking agent for pig manure composting. Hence, it was the aim of this project to evaluate the feasibility of co-composting pig manure with leaves with special emphasis on its effects on compost maturity and quality. Two piles were prepared with one pile (Pile A) just constituted of pig manureand sawdust at a mixing ratio of 3:2 (w/w, fresh weight), while the other one (Pile B) with pig manure, sawdust and leaves at 3:1:1 ratio (w/w, fresh weight) to achieve a C/N ratio of 30. Each 8 m3 heap was turned and mixed every 3 days to provide sufficient aeration and the moisture content was kept at 60-70% (w/w) throughout the composting period. After 49 days of composting, dissolved organic carbon (DOC), soluble NH4-N(solid), C/N(aqueous) and C/N(aqueous) of pile A decreased to <5%, 400 mgkg(-1), 20 and 6, respectively, indicating a high degree of maturity, while pile B with leaves required only 35days. Seed germination index (GI) of pile A increased to 66.5% at day 49, while pile B to 52.4% at day 35, which was higher than the phytotoxin-free level of 50% recommended for agricultural use. This demonstrated that the addition of leaves enhanced the humification process and shortened the time required for maturation and stabilization of pig manure composting. Therefore, it is recommended to co-compost pig manure with leaves to provide a means to reutilize this waste and in the same time to reduce the dependence on sawdust as a buLking agent. PMID- 11766043 TI - Cr(VI) reduction in aqueous solutions by using synthetic iron sulphide. AB - This study was carried out to reduce Cr(VI) in aqueous solutions by using synthetic iron sulphide. For that purpose, the effects of acid content, contact time, initial Cr(VI) concentration, temperature of the solution, particle size and dosage of iron sulphide on the Cr(VI) reduction were investigated. Reduction extent of Cr(VI) is, to a great extent, dependent on the amount of acid. The Cr(VI) in the solution containing two times the H2SO4 with respect to stoichiometric amount of Cr(VI) was completely reduced within 45 min by using 2.5 g litre(-1) iron sulphide at 25 degrees C. The reduction efficiency of Cr(VI) was increased with temperature of solution. The variation in particle size of iron sulphide did not affect the reduction yield of Cr(VI). The total reduction capacity of synthetic iron sulphide was found to be 237.6 mg Cr(VI) g(-1). The results related to shrinking particle model showed that the reduction reaction was chemically controlled and activation energy for theprocess was calculated as 38.4 kJ mol(-1). PMID- 11766044 TI - Nutrient removal with methanol as a carbon source full-scale continuous inflow SBR application. AB - Methanol was applied to a full-scale continuous inflow SBR, as a carbon source for denitrification and possible phosphorus removal. This research was conducted at the District of Kent Wastewater Treatment Plant in Agassiz, British Columbia, Canada. This plant employs two SBR's working in parallel; one unit was used as a control, without the addition of methanol. There was no difference in the overall total nitrogen removal efficiency through methanol addition, however,the additional carbon source significantly shortened the denitrification reaction time in the existing reactor. The high nitrogen removal efficiency, with or without methanol addition, was primarily due to the advantages provided by continuous-flow SBR carbon loading. The phosphorus removal efficiency in the experimental SBR was also consistently higher than in the control SBR. The solids production from methanol addition wa s estimated to vary between 0.18 and 0.29gVSS/gCH3OH. Methanol addition also had an influence on the settling qualities of the sludge. PMID- 11766045 TI - Effect of solid-liquid separation on BOD and VFA in swine manure. AB - Fresh swine manure was sieved into seven different particle size categories, i.e., <0.075 mm, < 0.15 mm, < 0.25 mm, < 0.5 min, < 1.0 mm, < 1.4 mm, and < 2.0 mm. Manure was stored in seven PVC columns and sampled every 5 days up to 30 days. Manure samples were analyzed for total volatile fatty acids (VFAs), 5-day biochemical oxygen demand (BOD5), total solids (TS), total suspended solids (TSS), and total volatile solids (TVS). Two parameters (VFAs and BOD5) were used to determine the odor generation potential of the test manure. The results showed that total VFAs correlated well with BOD5 (R2 = 0.8297). The levels of ISS only explained 40% of BOD5 and 46% of VFAs, both of which increased with storage time, regardless of solid particle sizes. Also, the data inferred that most of the odorous compounds (measured by VFA and BOD levels) were contained in manure solid particles less than 0.075 mm. These cannot be removed by commercial mechanical separators with screen size ranging from 0.5 to 3.0 mm. With an average separation efficiency of 25% for most commercially available mechanical separators, the removal efficiencies of BOD5 and VFAs were as low as 10% and 12%, respectively. These findings cannot justify the use of solid-liquid separation tocontrol odor. Data also showed that for swine manure, it is critical to run separation treatment within the first ten days after the manure is excreted to potentially improve the separation efficiency. After ten days, the degradation of TSS was accelerated due to the increased biological activities, which may greatly reduce the separation efficiency. PMID- 11766046 TI - Prediction of potential toxicity and side effect protein targets of a small molecule by a ligand-protein inverse docking approach. AB - Determination of potential drug toxicity and side effect in early stages of drug development is important in reducing the cost and time of drug discovery. In this work, we explore a computer method for predicting potential toxicity and side effect protein targets of a small molecule. A ligand-protein inverse docking approach is used for computer-automated search of a protein cavity database to identify protein targets. This database is developed from protein 3D structures in the protein data bank (PDB). Docking is conducted by a procedure involving multiple conformer shape-matching alignment of a molecule to a cavity followed by molecular-mechanics torsion optimization and energy minimization on both the molecule and the protein residues at the binding region. Potential protein targets are selected by evaluation of molecular mechanics energy and, while applicable, further analysis of its binding competitiveness against other ligands that bind to the same receptor site in at least one PDB entry. Our results on several drugs show that 83% of the experimentally known toxicity and side effect targets for these drugs are predicted. The computer search successfully predicted 38 and missed five experimentally confirmed or implicated protein targets with available structure and in which binding involves no covalent bond. There are additional 30 predicted targets yet to be validated experimentally. Application of this computer approach can potentially facilitate the prediction of toxicity and side effect of a drug or drug lead. PMID- 11766047 TI - Towards the design and computational characterization of a membrane protein. AB - The design of a transmembrane four-helix bundle is described. We start with an idealized four-helix bundle geometry, then use statistical information to build a plausible transmembrane bundle. Appropriate residues are chosen using database knowledge on the sequences of membrane helices and loops, then the packing of the bundle core is optimized, and favorable side chain rotamers from rotamer libraries are selected. Next, we use explicit physical knowledge from biomolecular simulation force fields and molecular dynamics simulations to test whether the designed structure is physically possible. These procedures test whether the designed protein will indeed be alpha-helical, well packed and stable over a time scale of several nanoseconds in a realistic lipid bilayer environment. We then test a modeling approach that does not include sophisticated database knowledge about proteins, but rather relies on applying our knowledge of the physics that governs protein motions. This independent validation of the design is based on simulated annealing and restrained molecular dynamics simulation in vacuo, comparable to procedures used to refine NMR and X-ray structures. PMID- 11766048 TI - Prediction of membrane protein orientation in lipid bilayers: a theoretical approach. AB - Over the past few years, several three-dimensional (3-D) structures of membrane proteins have been described with increasing accuracy, but their relationship with membranes are still not well understood. Recently, we have developed an empirical method, Integral Membrane Protein and Lipid Association (IMPALA), to predict the insertion of molecules (lipids, drugs) into lipid bilayers (Proteins 30 (1998) 357). The IMPALA uses a Monte Carlo minimisation procedure to calculate the depth and the angle of insertion of membrane-interacting molecules taking into account the restraints dictated by a lipid bilayer. In this paper, we use IMPALA to test the insertion of 23 integral membranous proteins (IMPs) and 2 soluble proteins into membranes. Four IMP are studied in detail: OmpA, maltoporin, MsCl channel and bacteriorhodopsin. The 3-D structures of the proteins are kept constant and the insertion into membrane is monitored by minimising the value of the restraint representing the sum of two terms, one for lipid perturbation and the other for hydrophobicity. The two soluble proteins are rejected from the membrane whereas, under the same conditions, all the membrane proteins remain inside, if the solvent accessible surface of the amino acids located inside the pore of porins is ignored. The results give the tilt angle of the IMP helices or strands with respect to the membrane surface and the depth of the protein mass centre insertion. We conclude that the restraint terms of IMPALA could be used to study the insertion of model structures or complexes of proteins within membranes. PMID- 11766049 TI - Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides. AB - When the oxygen atom in a peptide bond is replaced by a sulfur atom, the restriction in the available conformational space and the ability of thioamides to confer resistance to enzymatic degradation renders thioamides as potentially useful building blocks for drug design and protein engineering. The solvation free energy differences between conformers of the same dipeptide can be high. Yet, previous conformational studies, basing on the (phi, psi) conformational energy maps of thio-substituted dipeptides, neglected both explicit water interactions and free energy considerations. In this paper, the (phi, psi) conformational free energy maps are obtained by single umbrella sampling in an explicit water environment for both alanine dipeptide and the corresponding thioamide derivatives. The phi and psi angles for the minima in the relative energy maps calculated with dielectric of 80 are similar to the corresponding phi and psi angles in the relative free energy maps for both Ac-Ala-NHMe (Ac: acetyl; Ala: alanine) and Act-Alat-NHMe (Act: thio-acetyl; Alat: thio-alanine). However, some large differences between the relative energy and relative free energy of major minima indicate that the consideration of free energy is important in determination of the relative occupancy of particular minima. Free energy maps for both Ac-Ala-NHMe and Act-Alat-NHMe show that thio-substitution favors conformations where phi < 0 because of the deeper beta and alphaR minima. The changes in the position and relative stability of minima were explained in terms of the destabilization of the regions near phi = -120, 0 and 120, psi = 60, -60, 180, which correspond to the increased steric hindrance due to the bulkier sulfur atom. PMID- 11766050 TI - Weeds as a source of plant growth promoting rhizobacteria in agricultural soils. AB - The influence of plant growth promoting (PGP) activity of bacterial communities recovered from each of six weed species (barnyard grass (Echinochloa crusfalli (L.) Beauv.), corn spurrey (Spergula arvensis L.), goldenrod (Sonchus sp.), Italian ryegrass (Lolium multiflorum L.), lamb's-quarters (Chenopodium album L.), and quack grass (Agropyron repens (L.) Beauv.)) was examined in relation to the effect it had on the growth of the potato cultivar Russet Burbank. Bacterial species composition and community structure were compared, species-abundance relationships were determined, and those members conferring positive benefits for potato growth and development were identified. Of the genera identified, Bacillus, Arthrobacter, Stenotrophomonas, Acinetobacter, and Pseudomonas were the most common, and Stenotrophomonas maltophilia was the most frequent species recovered across all sources. Significantly higher population densities were found in the root zones of quack grass, compared with Italian ryegrass and lamb's quarters. There were no significant differences in species richness among the root zones; however, evenness indices (species distribution) were significantly lower in corn spurrey (P = 0.05). Significantly higher diversity indices (Hill-1 and Hill-2 numbers) (P = 0.05) were found in the root zone soil communities of potato and goldenrod, indicating a decrease in the proportional abundance of common and very abundant species, respectively, while in barnyard grass, corn spurrey, and Italian ryegrass the reverse was the case. In both years of the study, Italian ryegrass and corn spurrey were consistently better sources of PGP rhizobacteria for potatoes, significantly (P < 0.001) increasing the mean wet weight of shoots and roots in in vitro bacterization studies. Barnyard grass was a consistently poor source of such isolates. Species-abundance measures of root zone bacterial biodiversity were not found, in this instance, to be a particularly good predictor of the presence or absence of PGP rhizobacteria. We consider that the study of complementary crops and soil-conditioning treatments should not preclude the examination of weed species as possible beneficials, as alterations in rhizobacterial biodiversity and functional versatility can influence the numbers and types of PGP bacterial strains, and consequently may serve to improve soil quality. PMID- 11766051 TI - Characterization of hybrid biphenyl dioxygenases obtained by recombining Burkholderia sp. strain LB400 bphA with the homologous gene of Comamonas testosteroni B-356. AB - The bacterial degradation of polychlorinated biphenyls depends on the ability of the enzyme biphenyl 2,3-dioxygenase (BPDO) to catalyze their oxygenation. Analysis of hybrid BPDOs obtained using common restriction sites to exchange large DNA fragments between LB400 bphA and B-356 bphA showed that the C-terminal portion of LB400 alpha subunit can withstand extensive structural modifications, and that these modifications can change the catalytic properties of the enzyme. On the other hand, exchanging the C-terminal portion of B-356 BPDO alpha subunit with that of LB400 alpha subunit generated inactive chimeras. Data encourage an enzyme engineering approach, consisting of introducing extensive modifications of the C-terminal portion of LB400 bphA to extend BPDO catalytic properties toward polychlorinated biphenyls. PMID- 11766052 TI - Efficient and predictable recovery of viruses from water by small scale ultrafiltration systems. AB - Current methods to concentrate viruses from large volumes of water are prone to inconsistent results and are costly and complex procedurally. Ultrafiltration can utilize size exclusion rather than adsorption and (or) elution to concentrate viruses and, therefore, may offer greater flexibility in developing methods that can provide more consistent recoveries among different viruses and widely varying water conditions. Two small scale ultrafiltration systems (hollow fiber and tangential flow) were tested with a virus suspended in 2 L of reagent grade, tap, ground, or surface water. Three model viruses were used (bacteriophages PP7 and T1 and poliovirus) to compare and characterize the recovery of viruses with the two ultrafiltration systems. Pretreatment of the ultrafilters with blocking agents and the use of elution agents can serve to prevent viral adsorption to the filter surface or to elute bound virus and keep viral agents suspended in the retentate. The use of a blocking and elution step concentrated viruses (>60% recovery) from widely varying water qualities, including surface water, such that a single method can be used to efficiently concentrate viruses from all of the water types tested. Both ultrafiltration systems appear to be able to efficiently recover viruses; however, the hollow fiber systems provided slightly better results in the 2-L volumes tested. PMID- 11766053 TI - Mycelial differentiation and spore formation by Streptomyces brasiliensis in submerged culture. AB - Streptomyces brasiliensis ATCC 23727 showed extensive sporulation when cultured in a liquid medium containing galactose and glutamic acid as carbon and nitrogen sources. Sporogenic hyphae formed under these conditions were morphologically similar and developmentally equivalent to aerial hyphae and metamorphosed into chains of spores by following a sequence of ultrastructural changes similar to that observed during growth on solid media. In addition, our electron microscopy study revealed two previously unrecognized aspects of hyphal development in streptomycetes: the formation of sporogenic hyphae was always preceded by changes in the structure of the nucleoid, and the sheath that characteristically covered these hyphae was not deposited coincidently with wall formation in the apical growing portion of the hypha. PMID- 11766054 TI - Enteric bifidobacteria: isolation from human infants and challenge studies in mice. AB - Bifidobacteria from breast-fed infants, formula-fed infants, or premature babies fed by parenteral methods were isolated and identified. The persistence of these microorganisms in the gastrointestinal tract of mice, after oral administration, was studied to determine the optimal dose and frequency of translocation to the liver and spleen. The rate of isolation among infants varied between 19 and 82% depending on the origin of the samples, with the highest values seen in breast fed babies. The predominant species found in all cases was Bifidobacterium adolescentis. The optimal dose for oral administration of bifidobacteria to mice was 10(7) cells per day per animal for up to 2, 5, or 7 days. These bacteria remained up to 5 days postfeeding, even if feeding was interrupted. The results of bacterial translocation assays showed differences for the different strains and doses tested. PMID- 11766055 TI - Salicylate inhibits the translation and transcription of ompF in Escherichia coli. AB - OmpF is a major outer membrane protein in Escherichia coli whose expression is regulated by a large number of factors, including the osmolarity of the growth medium and the concentration of salicylate. We have previously shown that at low osmolarity, OmpF is post-transcriptionally regulated by micF mRNA, and that at high osmolarity, regulation occurs primarily by the inhibition of transcription by OmpR (Ramani et al. 1994). In contrast, salicylate was reported to alter OmpF expression solely by blocking translation primarily through micF mRNA (Rosner et al. 1991). We examined the effect of salicylate by analyzing the levels of OmpF in wild-type and micF strains grown with salicylate. At low concentrations of salicylate (0-4 mM), OmpF levels were inhibited strongly in wild-type cells, whereas no inhibition of OmpF was observed in the micF strain. At high concentrations of salicylate (10-20 mM), both the wild type and the micF strain showed strong inhibition of OmpF. To study the effect of salicylate on transcription, ompF mRNA and micF mRNA were analyzed in wild-type cells. micF mRNA levels increased during growth with 1, 2, and 4 mM salicylate. In contrast, ompF mRNA levels were not affected by low concentrations of salicylate, but decreased strongly at 10 and 20 mM salicylate. Taken together, these results suggest that similar to osmoregulation, salicylate inhibits both the translation and transcription of ompF. PMID- 11766056 TI - Co-inoculation with Bacillus sp. CECT 450 improves nodulation in Phaseolus vulgaris L. AB - The strain Bacillus sp. CECT 450 increased nodulation on bean (Phaseolus vulgaris L.) when co-inoculated with Rhizobium tropici CIAT 899. This positive effect occured under controlled conditions on perlite-vermiculite, sand, or in a mixture of soil and sand. This increase was also observed in a field assay. Nodulation kinetic studies suggested that the synergistic effect is pronounced during the latter stages of cultivation. In contrast, the same bacteria co-inoculated with Bradyrhizobium japonicum USDA 110 reduced nodulation on soybean (Glycine max (L.) Merr.). Inoculation with Bacillus sp. CECT 450 alone had no effect on bean plants, but reduced root growth in soybean. The survival of Bacillus sp. CECT 450 on inoculated seeds was high, even when inoculated seeds were maintained for several months at room temperature. PMID- 11766057 TI - Phosphite disrupts the acclimation of Saccharomyces cerevisiae to phosphate starvation. AB - The influence of phosphite (H2PO3-) on the response of Saccharomyces cerevisiae to orthophosphate (HPO4(2-); Pi) starvation was assessed. Phosphate-repressible acid phosphatase (rAPase) derepression and cell development were abolished when phosphate-sufficient (+Pi) yeast were subcultured into phosphate-deficient (-Pi) media containing 0.1 mM phosphite. By contrast, treatment with 0.1 mM phosphite exerted no influence on rAPase activity or growth of +Pi cells. 31P NMR spectroscopy revealed that phosphite is assimilated and concentrated by yeast cultured with 0.1 mM phosphite, and that the levels of sugar phosphates, pyrophosphate, and particularly polyphosphate were significantly reduced in the phosphite-treated -Pi cells. Examination of phosphite's effects on two PHO regulon mutants that constitutively express rAPase indicated that (i) a potential target for phosphite's action in -Pi yeast is Pho84 (plasmalemma high-affinity Pi transporter and component of a putative phosphate sensor-complex), and that (ii) an additional mechanism exists to control rAPase expression that is independent of Pho85 (cyclin-dependent protein kinase). Marked accumulation of polyphosphate in the delta pho85 mutant suggested that Pho85 contributes to the control of polyphosphate metabolism. Results are consistent with the hypothesis that phosphite obstructs the signaling pathway by which S. cerevisiae perceives and responds to phosphate deprivation at the molecular level. PMID- 11766058 TI - Selective isolation and study on the global distribution of the genus Planobispora in soils. AB - Planobispora strains, including the type strain, produced abundant sporangia on humic acid-vitamin gellan gum medium when more than 50 colonies grew on a plate. However, these strains did not produce sporangia on the aerial mycelium, a diagnostic characteristic of this genus, when fewer than 20 colonies grew on a plate. Trace salts, such as FeSO4 x 7H2O, MnCl2 x 4H2O, ZnSO4 x 7H2O, and NiSO4 x 6H2O, stimulated sporangium formation of Planobispora strains. Better sporangium formation of Planobispora strains was observed on the humic acid-trace salts gellan gum medium at pH 9.0 than at neutral pH. Moreover, an alkaline medium repressed the growth of three out of six Streptomyces strains so that this condition was effective for selective isolation of Planobispora strains. An alkaline flooding solution of skim milk, five antimicrobial agents, and dry heat treatment at 90 degrees C for 60 min were effective for selective isolation. Using these techniques, we examined the distribution of Planobispora strains by using 1467 soil samples collected from Japan and other parts of the world. One hundred and nineteen Planobispora strains were isolated from 51 soil samples (3.5% of the samples tested) that were collected in Ecuador, Egypt, French Guiana, India, and Madagascar. Planobispora strains were recovered only in tropical and subtropical soils. To our knowledge, this is the first record that Planobispora strains have been isolated from locations other than Venezuela, Namibia, or South Africa. PMID- 11766059 TI - Role of oxidative stress and thiol antioxidant enzymes in nickel toxicity and resistance in strains of the green alga Scenedesmus acutus f. alternans. AB - Treatment with Ni(NO3)2 leads to the formation of reactive oxygen species (ROS) in the green alga Scenedesmus acutus f. alternans, causing lipid peroxidation. This effect was stronger in a Ni-sensitive strain, UTEX72, than in a Ni-resistant strain, B4. In the resistant strain, Ni induced an increased ratio of reduced to oxidized glutathione (GSH:GSSG), whereas it caused a lowered ratio in the sensitive strain. Enzymes involved in the control of ROS were studied in these strains as well as two others that have shown different degrees of nickel resistance. The resistant strain, B4, which grows while containing large amounts of internal Ni, had much higher levels of glutathione reductase and catalase than the other strains. The sensitive strain, UTEX72, had higher levels of glutathione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase than did strain B4. The resistant strains, Ni-Tol and Cu-Tol, derived from strain UTEX72, which are partly able to exclude Ni, had enzyme profiles that resembled that of UTEX72 more closely than that of B4. Treatment with 10 and 100 microM Ni for 4 or 22 h had complex effects on enzyme levels in all four strains. Ni decreased glutathione reductase in B4, slightly increased it in Ni-Tol and Cu-Tol, and did not affect the low levels of this enzyme in UTEX72. Ni lowered glutathione peroxidase in B4 and either did not affect it or slightly raised it in the other strains. Ni lowered catalase in B4 and did not affect the other strains. Superoxide dismutase was raised in B4 and Ni-Tol and lowered in Cu-Tol and UTEX72, and glucose-6-phosphate dehydrogenase was lowered in all four strains. These results suggest that one major mechanism of Ni resistance, especially in strain B4, may be the ability to combat the formation of ROS when exposed to this metal, likely by maintaining a high GSH:GSSG ratio. PMID- 11766060 TI - Physical, chemical, and microbiological characteristics of microbial mats (kopara) in the South Pacific atolls of French Polynesia. AB - Microbial mats that develop in shallow brackish and hyposaline ponds in the rims of two French polynesian atolls (Rangiroa and Tetiaroa) were intensively investigated during the past three years. Comparative assessment of these mats (called kopara in polynesian language) showed remarkable similarities in their composition and structure. Due to the lack of iron, the color of the cyanobacterial pigments produced remained visible through the entire depth of the mats (20-40 cm depth), with alternate green, purple, and pink layers. Profiles of oxygen, sulfide, pH, and redox showed the anoxia of all mats from a depth of 2-3 mm. Analyses of bacterial pigments and bacterial lipids showed that all mats consisted of stratified layers of cyanobacteria (mainly Phormidium, Schizothrix, Scytonema) and purple and green phototrophic bacteria. The purple and green phototrophic bacteria cohabit with sulfate reducers (Desulfovibrio and Desulfobacter) and other heterotrophic bacteria. The microscopic bacterial determination emphasized the influence of salinity on the bacterial diversity, with higher diversity at low salinity, mainly for purple nonsulfur bacteria. Analyses of organic material and of exopolymers were also undertaken. Difference and similarities between mats from geomorphological, microbiological, and chemical points of view are discussed to provide multicriteria of classification of mats. PMID- 11766061 TI - Modulation of interaction between left ventricular ejection and the arterial compartment: assessment of aortic wave travel. PMID- 11766062 TI - Conventional coronary artery bypass grafting in patients with total occlusion of the internal carotid artery. AB - The number of patients with coexisting disease of the coronary and carotid arteries is increasing. Patients with total occlusion of the carotid artery may have a higher risk of stroke during cardiopulmonary bypass surgery and in the perioperative period. We report our results for coronary artery bypass grafting (CABG) in patients with total occlusion of the carotid artery. We examined 269 patients who underwent carotid artery duplex scanning (CADS) before CABG between November 1995 and January 1998. Among them, 11 patients (4.1%) had total occlusion of a carotid artery. Four patients underwent elective CABG and five underwent emergency CABG. One patient underwent anastomosis of the superficial temporal artery to the middle cerebral artery (STMC) and one patient underwent a combined CABG and carotid endoarterectomy (CEA) procedure. A transient neurological event occurred in only one patient (9.1%). The other patients recovered uneventfully. Our results suggest that CABG can be performed without stroke in patients with total unilateral occlusion of a carotid artery using our strategies. PMID- 11766063 TI - Hyperfibrinogenemia increases the risk of cardiac events after coronary artery stenting. AB - Primary success rates, and the angiographic and clinical outcome after percutaneous coronary intervention, are influenced by many different factors. Clinical features and morphologic characteristics of the target lesion are important. Also, interventionally caused endothelial trauma may trigger atherogenetic and procoagulatory factors leading to intraluminal thrombosis. The study population consisted of 228 consecutive, unselected patients with symptomatic coronary artery disease or exercise-induced myocardial ischemia and coronary artery stenoses eligible for percutaneous intervention. We analyzed different clinical, morphological, and laboratory (total cholesterol, high density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, fibrinogen) features in those patients with adverse cardiac events (stent thrombosis, myocardial infarction, urgent target vessel revascularization, death) after primary successful coronary artery stenting, compared with a control group without adverse events. In the group with adverse cardiac events we found a significantly higher level of fibrinogen compared with the control group. Other laboratory data and clinical characteristics were not significantly different between the two groups. The study shows a possible association between hyperfibrinogenemia and adverse cardiac events after intracoronary stenting. In clinical practice, the potential role of elevated levels of fibrinogen in an unfavorable outcome after percutaneous coronary interventions should be considered when planning coronary artery stenting. PMID- 11766064 TI - N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly improves postischemic left ventricular dysfunction. AB - We examined whether pharmacological inhibition of glycogenolysis by N-methyl-1 deoxynojirimycin (MOR-14), a new compound which reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase activity of the glycogen-debranching enzyme, can protect the heart against postischemic left ventricular dysfunction. The hearts of male Sprague-Dawley rats were excised, and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during the ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s), and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min including a 30-min preischemic period followed by a 30-min episode of global ischemia and 60 min reperfusion. with or without 0.5 or 2 mM of MOR-14 during the 30-min preischemic period or the first 30 min of reperfusion. In another series of experiments, the myocardial content of glycogen and lactate was measured during the 30-min episode of ischemia in groups treated with and without 2mM of MOR-14. Preischemic but not postischemic treatment with MOR-14 significantly improved LVDP and +/-dP/dt without altering coronary flow during reperfusion in a dose-dependent manner. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during the 30-min episode of ischemia. Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart. PMID- 11766065 TI - Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans. AB - It is of great interest and value to evaluate the systemic nitric oxide (NO) production rate in humans under various conditions. However, the currently available estimation methods are troublesome and time-consuming. We thus aimed at developing a simple method to estimate the basal systemic NO production rate in humans based on a steady-state analysis, i.e., a balance between the systemic NO production rate and the total nitrate elimination rate. Plasma nitrate concentrations of young healthy volunteers (n = 7 in group 1: n = 9 in group 2) were measured for 2 days. In group 1, all subjects had the same meals for 7 days prior to the plasma nitrate measurement. In group 2, all subjects were allowed free diets. The plasma nitrate concentrations were highly influenced by dietary nitrite/nitrate intake in both groups and reached the steady-state levels after 14-h fasting. Accordingly, the basal systemic NO production rates were estimated from the plasma nitrate concentrations after 14-h fasting (group 1, 630 +/- 37 nmol min(-1) = 0.78 +/- 0.03 micromol kg(-1) h(-1); group 2, 597 +/- 45 nmol min( 1) = 0.66 +/- 0.05 micromol kg(-1) h(-1), P = not significant vs group 1). These estimated values were comparable to the values obtained by other methods. In conclusion, the present estimation method with 14-h fasting using a single compartment analysis was found to be a simple approach to quantitative evaluation and intra- and interindividual comparisons of the basal systemic NO production rates in humans. PMID- 11766066 TI - Mental stress and physical exercise increase platelet-dependent thrombin generation. AB - Thrombin generation is an important factor in the pathogenesis of thrombogenic disorders and acute coronary syndromes. Increase in mental stress has been associated with the initiation of the acute coronary syndromes, but the exact mechanism is not known. The present study examined the effects of physical exercise and mental stress on platelet-dependent thrombin generation. Twelve healthy men (mean age 34.2 +/- 2.4 years) underwent a treadmill exercise test and a mental stress test by performing mental arithmetic. Platelet-dependent thrombin generation and plasma concentrations of catecholamines, thrombin-antithrombin III complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), and plasminogen activator inhibitor-1 (PAI-1) were measured before, immediately after, and at 10 and 30 min after stress. Thrombin generation increased significantly immediately after exercise, followed by rapid normalization. Mental stress caused a significant increase in thrombin generation 10 min after stress. While plasma concentrations of epinephrine, norepinephrine, and dopamine were elevated immediately after exercise, and rapidly returned to baseline, only plasma norepinephrine increased immediately after mental stress. TAT and PIC concentrations did increase immediately after exercise; however, PAI-1 remained unchanged. The increase in thrombin generation with exercise and mental stress was unaffected by treatment with 81 mg/day of aspirin of 7 days. However, it was inhibited by a single oral 40-mg dose of metoprolol. Both exercise and mental stress cause an increase in platelet-dependent thrombin generation, which was suppressed by beta-blocker therapy, but not by aspirin. PMID- 11766067 TI - Giant extracardiac unruptured aneurysm of the sinus of Valsalva: a case report. AB - Extracardiac unruptured aneurysm of the sinus of Valsalva (ASV) is rare and difficult to diagnose accurately by echocardiography or cardiac catheterization preoperatively. A 63-year-old woman, with dyspnea and palpitations, diagnosed with aortic regurgitation (AR) with congestive heart failure and extracardiac unruptured ASV, was referred to our hospital for surgical repair. The unruptured ASV was well visualized by magnetic resonance imaging (MRI), and diagnosed as an extracardiac type. Surgical repair was performed by aortic valve replacement and aneurysmectomy. It was concluded that early surgical repair of extracardiac ASV should be considered to prevent sudden death, and MRI is an accurate and useful method for preoperative diagnosis. PMID- 11766068 TI - A case report of intravenous leiomyomatosis extending into the heart. AB - The patient was a 47-year-old woman who underwent total hysterectomy for uterine leiomyoma in 1994. Two years later, intracaval and intravenous tumors were found by ultrasonic cardiography, magnetic resonance imaging, enhanced chest computed tomography, and venography. The patient underwent total removal of these tumors. Pathological findings indicated that these tumors were leiomyomas. After comparing the present findings with those of similar cases in the literature, we concluded that our patient had intravenous leiomyomatosis extending into the heart. PMID- 11766069 TI - Antiplatelet therapy for a pregnant woman with a mechanical aortic valve: report of a case. AB - A 24-year-old woman, who had undergone an aortic valve replacement with a 21-mm St. Jude Medical mechanical aortic valve, wished to have a child. She visited our department because she was aware of the risks associated with pregnancy while undergoing anticoagulant therapy using warfarin potassium. The patient opted to undergo the recommended alternative method involving the use of antiplatelet agents (dipyridamole, ticlopidine, and aspirin) in place of warfarin potassium. Antiplatelet agents were administered while regularly monitoring the platelet aggregability along with the coagulation and fibrinolytic activity. At the 36th week of gestation, antiplatelet agents were discontinued and instead were followed by continuous heparin infusion. A healthy baby was delivered by cesarean section without any complications at the 38th week. Antithrombotic therapy using antiplatelet agents appears to be an effective option for preventing serious problems for pregnant women with a mechanical heart valve. PMID- 11766070 TI - Abnormal esophageal anatomy associated with a congenital diaphragmatic hernia: report of a case. AB - Gastroesophageal reflux associated with anatomic and functional abnormalities of the esophagus may be encountered following the repair of a congenital diaphragmatic hernia (CDH). We report herein the case of a newborn male infant with CDH found to have an air-filled paravertebral structure. Upper gastrointestinal series confirmed the presence of an ectatic esophagus with poor peristalsis and severe gastroesophageal reflux. The patient required jejunostomy after a safe period of total parenteral nutrition. He tolerated oral feeding following medical treatment without the need for antireflux surgery. The association of dysphagia, esophageal ectasia, and gastroesophageal reflux is rarely seen with CDH, and feeding intolerance is a self-limited disorder that does not usually necessitate antireflux surgery. PMID- 11766071 TI - Portal venous dilatation and stenting for bleeding jejunal varices: report of two cases. AB - We present two patients who underwent a portal stent placement for bleeding jejunal varices of the afferent loop caused by extrahepatic portal venous stenosis. Case 1 involved a 66-year-old woman who developed bleeding jejunal varices due to extrahepatic portal venous stenosis 1 year after a pancreaticoduodenectomy with intraoperative radiation therapy. Percutaneous transhepatic balloon dilatation and stent placement were performed. Since undergoing the procedure, no bleeding has occurred. Case 2 concerned a 44-year old woman who had a rupture and bleeding of jejunal varices 16 years after a choledocojejunostomy. Stenosis was observed from the right and left branches of the portal vein to its intrahepatic branches. Both balloon dilatation and stent placement were attempted. However, the stent could not be fully inserted into the intrahepatic portal vein. Portal stent placement is less invasive and radical, and therefore should be attempted for the treatment of extrahepatic portal venous stenosis. However, there are limits to its application if the stenosis extends to the intrahepatic branches of the portal vein. PMID- 11766072 TI - Mucinous cystadenocarcinoma in the appendix in a patient with nonrotation: report of a case. AB - Mucinous cystadenocarcinoma in the appendix is uncommon. An anomaly in the rotation of the intestine is also uncommon in adults. We herein report a case of mucinous cystadenocarcinoma in the appendix in a patient with nonrotation. To the best of our knowledge, this is the first report of appendiceal carcinoma in a patient with an anomaly of intestinal rotation. A 76-year-old woman was admitted to our hospital with left low abdominal pain. Physical examination revealed tenderness with muscle rigidity in the left lower quadrant. The patient was diagnosed to have intussusception by computed tomography and ultrasonography. An emergency operation showed nonrotation and the top of the appendix situated in the left iliac fossa. An appendectomy was performed because of gangrenous acute appendicitis. However, the cut surface of the appendix showed a mucocele measuring 4 x 4 cm in size. It was diagnosed to be mucinous cystadenocarcinoma histopathologically. A right hemicolectomy with lymph node dissection was performed, and no remaining cancer cells or lymph node metastases were found in the resected specimen pathologically. The patient had an uneventful postoperative course. No signs of recurrence have been observed for 23 months since her last operation. PMID- 11766073 TI - Non-Hodgkin's lymphoma of the ascending colon in a patient with becker muscular dystrophy: report of a case. AB - We herein present the findings of a 10-year-old boy with non-Hodgkin's lymphoma of the ascending colon which caused intussusception and intestinal bleeding. He had a history of Becker muscular dystrophy. However, he had neither hypertrophic calves nor cardiomyopathy, and his serum creatine kinase (CK) level always exceeded 2000 IU/l. Preoperatively, a laboratory examination revealed high serum levels of CK (2038IU/l), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and the blood hemoglobin level was 7.0g/dl. A barium enema examination revealed an intussusception in his ascending colon, which was found to be a highly vascular tumor on Doppler ultrasound scans. A right hemicolectomy was performed. Macroscopically, the 5 x 6 x 8-cm solid tumor of the ascending colon resembled a submucosal tumor and had two ulcerous lesions at the tip. The tumor was histologically diagnosed to be a diffuse large B-cell lymphoma of the ascending colon. General examinations revealed no involvement of lymphoma postoperatively. At 13 months after surgery, the CK (37861U/l), AST (110lU/l), ALT (1381U/ l), and LDH (420lU/l) levels are still high, and the patient is doing well without any signs of recurrence. PMID- 11766074 TI - Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case. AB - We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP. PMID- 11766075 TI - Right hepatic segmentectomy for the treatment of intrahepatic biliary stones due to ascaris lumbricoides: report of a case. AB - We report herein the case of a 46-year-old woman investigated for recurrent acute cholangitis. Ultrasound, endoscopic retrograde cholangiopancreatography, and computed tomography scan revealed dilatation and multiple images suggestive of intrahepatic biliary stones in the ducts that drained segments V and VI of the liver. Endoscopic treatment was attempted unsuccessfully, and based on the severity of the last crisis of cholangitis a laparotomy was performed. A right hepatic lobectomy including segments V and VI was carried out without any complications, resulting in complete relief of symptoms. Pathological examination of the liver demonstrated the presence of worm nests in the liver parenchyma with chronic granulomatous lesions. PMID- 11766076 TI - Pancreatitis induced by valproic acid: report of a case. AB - A 22-year-old woman with intellectual impairment, who had been taking valproic acid continuously for 19 years since being diagnosed with epiloia at the age of 3 years, presented to our hospital following the sudden development of epigastric pain. An abdominal computed tomography scan revealed acute exacerbation of chronic pancreatitis. Conservative treatment was initiated, despite which the pancreatitis became exacerbated, necessitating resection of the pancreatic head and duodenum. Histological examination of the resected specimens revealed a large number of pancreatic calculi in the main pancreatic duct, suggesting chronic pancreatitis with fibrosis at the periphery. The incidence of pancreatitis developing in association with valproic acid is unclear; however, only 40 such cases have been reported in the English literature. Most of the patients previously described presented with acute pancreatitis in the initial stage. However, the clinical course of our patient, with acute exacerbation following a relatively chronic course, was different from those previously described, suggesting the presence of chronic pancreatitis related to valproic acid. PMID- 11766077 TI - Spontaneous rupture of the pancreaticoduodenal artery possibly related to prior occlusion of the common hepatic artery: report of a case. AB - We report herein a case of spontaneous rupture of the pancreaticoduodenal artery (PDA) associated with obstruction of the common hepatic artery. A 68-year-old man was admitted to our hospital following the sudden onset of severe upper abdominal pain. Computed tomography revealed a large mass formation in the peritoneal cavity. Hemorrhagic shock rapidly developed during the initial evaluation, necessitating an exploratory laparotomy to be performed in the emergency room. This revealed a large hematoma in the retroperitoneal space, and a ruptured PDA was sutured. Postoperative angiography showed obstruction of the common hepatic artery and also suggested that the source of the bleeding was the PDA. Thus, a diagnosis of spontaneous rupture of a PDA aneurysm associated with occlusion of the common hepatic artery was made. Following this case report, we discuss the development of true aneurysms of the PDA and the treatment of ruptured true PDA aneurysms resulting in shock. PMID- 11766078 TI - Autoantibody to gravin is expressed more strongly in younger and nonthymomatous patients with myasthenia gravis. AB - Gravin is expressed in several cell and tissue types as either 300 kDa doublet or 250 kDa proteolytic products. It is a cytoplasmic antigen that reacts with the serum of patients with myasthenia gravis (MG). Autoantibodies to gravin residues 1477-1781 are highly specific for MG. In the present study, we examined residues 1477-1781 in detail and found that residues 1542-1547 of gravin protein, which had sequence homology with the binding sequences of two protein A-kinase anchoring proteins, were highly reactive to MG serum. Antigravin antibody activities were stronger in younger and nonthymomatous patients. These findings suggest that antigravin antibody activities could be a useful prognostic factor and that the gravin antibody of MG may have a function which prevents the protein A-kinase binding pathway. PMID- 11766079 TI - Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms. AB - Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors. PMID- 11766080 TI - Abdominal vascular injuries: the trauma surgeon's challenge. PMID- 11766081 TI - Indications, risks, and acceptance of total thyroidectomy for multinodular benign goiter. AB - Selective morphology- and function-adapted resection is generally regarded as the surgical treatment of choice for benign goiter causing iodine deficiency. This procedure aims to reduce the need for patients to undergo reoperations for recurrence by completely removing all nodules. However, to achieve this sometimes requires a total thyroidectomy, the option of which is often rejected because of a presumed higher rate of complications. In this study, 324 patients who underwent total thyroidectomy were evaluated retrospectively. The patients were interviewed about their postoperative course and their acceptance of the procedure performed. The complications were compared with those associated with subtotal resection or hemithyroidectomies performed in our collective experience. The rate of complications associated with total thyroidectomy, namely, recurrent nerve palsy in 0.9%, hypocalcemia in 0.9%, wound infection in 0.9%, and secondary hemorrhage in 0.6%, did not differ significantly from that associated with subtotal resections/ hemithyroidectomies. Moreover, 88.3% of the patients who underwent total thyroidectomy were satisfied with the results of surgery. These findings indicate that total thyroidectomy is an acceptable surgical alternative for benign multinodular goiters. PMID- 11766082 TI - Differences in the progesterone receptor contents between familial breast cancers and sporadic breast cancers stratified by patient age. AB - In the present study, we investigated the estrogen (ER) and progesterone receptor (PR) contents of familial breast cancers (FBCs) and compared the findings with those of sporadic breast cancers., stratified by the patients' age. To evaluate the hormone receptor contents of Japanese FBCs, we collected a consecutive series of 250 FBCs and 2,533 sporadic breast cancers (SBCs). These patients were divided into the three groups stratified by the patients' age at initial surgery (group I, under 40 years old; group II, 40-60 years old; group III, over 60 years old). The clinicopathological features of FBCs and SBCs, including ERs and PRs, were analyzed for each group. In all age groups, the PR contents of FBCs were significantly lower than those of SBCs, particularly for group III. In FBCs, the PR content was significantly lower in group III than in groups I or II. In addition, there was a nonsignificant trend towards a high frequency of ER positive, PR-negative tumors in FBC patients aged 60 years and over. These data indicate that the loss of ER function and/or loss of binding capacity of PR to progesterone was associated with some late-onset FBCS. PMID- 11766083 TI - Surgical approach for repair of descending thoracic aortic aneurysms and postoperative respiratory function. AB - Good exposure and the minimization of lung and thorax injuries are important objectives of surgery for descending thoracic aortic aneurysm (DTAA). In this study, three surgical approaches for DTAA were compared to assess postoperative respiratory function. The subjects were 21 patients with DTAA, three of whom had a thoracoabdominal aneurysm. The mean age was 61 years, and there were 12 men and 9 women. The causes of aneurysm were atherosclerosis in 16 patients, chronic dissection in 4, and traumatic pseudoaneurysm in 1. All the patients underwent femoro-femoral partial cardiopulmonary bypass. The DTAA was replaced with a prosthetic graft in 18 patients and repaired with a patch graft in 3. Three approaches were selected, namely, posterolateral thoracotomy (PL group, n = 12), median sternotomy combined with anterolateral thoracotomy (M group, n = 5), and spiral incision (S group, n = 4). There were no significant differences in operation time, cardiopulmonary bypass time, intraoperative blood loss volume, or water balance. The duration of respiratory support and intensive care unit stay were significantly (P < 0.05) longer in the M group than in the other two groups. The alveolararterial oxygen difference (AaDO2) and respiratory index (RI) levels immediately after surgery were also significantly (P < 0.05) higher in the M group than in the PL group. There were no significant differences in AaDO2 and RI levels 12 and 24h after surgery among the three groups. These results suggest that posterolateral thoracotomy is a desirable surgical approach for DTAA repair in view of the fact that it has the least effect on postoperative respiratory function. PMID- 11766084 TI - Beneficial effects of immediate enteral nutrition after esophageal cancer surgery. AB - This study was conducted to determine the effects of immediate enteral nutrition (EN) on nutritional status, immunological competence, and the suppression of excessive inflammatory responses in patients following esophageal cancer surgery. Twenty-four patients who underwent the same elective operation for thoracic esophageal carcinoma were randomized into an immediate enteral nutrition (IEN) group who received EN from postoperative day (POD) 1 and a parenteral nutrition (PAN) group. Both groups received comparable volumes and calories on the same POD. Laboratory studies were carried out preoperatively and on PODs 1-7. Other nutritional and immunological assessments were repeated on PODs 1 and 7. Plasma concentrations of nitrate and nitrite were also measured. All of the patients in the IEN group tolerated enteral feeding well. There were no significant differences in the results of nutritional assessments, lymphocyte function, or plasma nitrate and nitrite levels between the two groups. The IEN group showed a significantly earlier recovery of the total lymphocyte count. The serum levels of total bilirubin and C-reactive protein were significantly attenuated in the IEN group. These results indicate that immediate EN may have beneficial effects on immunological competence and the suppression of excessive inflammatory responses in patients following esophagectomy. Patients undergoing radical esophageal surgery who are subjected to severe surgical stress might benefit the most from early EN. PMID- 11766085 TI - Impact of oral antimicrobial prophylaxis on surgical site infection and methicillin-resistant Staphylococcus aureus infection after elective colorectal surgery. Results of a prospective randomized trial. AB - The impact of oral antimicrobial prophylaxis on the surgical site infection and methicillin-resistant Staphylococcus aureus (MRSA) infection after elective colorectal surgery was evaluated by a prospective randomized single-blind study. The patients were randomly allocated to receive either mechanical bowel cleansing with polyethylene glycol alone (group 1) or mechanical cleansing plus oral antimicrobial prophylaxis with kanamycin and erythromycin for 2 days prior to surgery (group 2). In both groups, cefotiam was intravenously given twice a day for 3 days. A total of 143 patients (71 for group 1 and 72 for group 2) were eligible. The incidence of a surgical site infection was 23.9% in group 1 and 11.1% in group 2 (P = 0.04). The incidence of MRSA infection including at surgical and remote sites was 11.1% in group 1 and 5.6% in group 2 (P = 0.19). A multivariate logistic regression analysis showed that the risk of surgical site infection was influenced by the choice of the chemical bowel preparation (P = 0.03) and blood loss (P < 0.01), while an MRSA infection was predominantly influenced by blood loss (P < 0.01) followed by coexisting underlying diseases (P = 0.07). These results suggest that preoperative antimicrobial prophylaxis would be useful for reducing the incidence of a surgical site infection without increasing the risk of an MRSA infection following elective colorectal surgery. PMID- 11766086 TI - Repeated hepatic dearterialization for unresectable carcinomas of the liver: report of a 10-year experience. AB - The effectiveness of repeated hepatic dearterialization (RHD) therapy was evaluated in 26 patients with unresectable primary and secondary liver tumors. RHD was performed in 12 patients with hepatocellular carcinoma (HCC), 7 with hepatic metastases from colorectal carcinoma, and 7 with hepatic metastases from gastric carcinoma. It was repeatedly carried out by occluding the hepatic artery for 1 h twice daily. All patients concurrently received an intra-arterial infusion of anticancer drugs. More than 50% remission of the hepatic tumors, defined as a partial response (PR), was demonstrated in 8 patients (31%). A higher PR was seen in hepatic tumors from metastatic gastric cancer (5 out of 7 patients; 71%). Most patients who suffered severe complications had HCC with liver cirrhosis. These preliminary results suggest that RHD with intra-arterial chemotherapy is an acceptable palliative treatment for patients with unresectable liver metastasis from gastric cancer; however, the majority of patients with HCC are not responsive to such treatment, primarily because most have underlying cirrhosis predisposing to the development of postoperative complications at an unacceptably high rate. PMID- 11766087 TI - Changes in arterial and portal perfusion in embolized and nonembolized hepatic lobes after portal vein embolization evaluated by helical computed tomography. AB - We evaluated the changes in hepatic arterial and portal perfusion in nonembolized as well as in embolized lobes after portal venous branch embolization (PVE) with dynamic helical computed tomography (CT). Six patients with hepatic malignancies, who underwent PVE prior to a subsequent hepatectomy, were the subjects of this study. We performed CT examinations before PVE and 2 weeks after PVE to make a volumetric analysis. At the same time, we performed single-location dynamic sequences after the injection of a 50-ml bolus of contrast medium, and we then created time-density curves from circular regions of interest drawn over the aorta, parenchyma of the right and left lobe of the liver, and spleen. We calculated the arterial perfusion index (ml/min per ml of tissue) and the portal perfusion index by dividing the maximum rate of enhancement of the liver before and after the splenic peak by the peak aortic enhancement. We then calculated the arterial and portal flows (ml/min) from the perfusion index and values of CT volumetry. In the right lobe, where the portal flow was occluded, the arterial perfusion index and flow increased significantly after PVE. In contrast, the arterial perfusion index and flow both decreased in the left lobe after PVE in a reverse response to the increase in the portal perfusion index and flow. The total arterial flow of the liver thus seemed to slightly increase; however, the change was not significant. By performing PVE an increased arterial perfusion was induced in the embolized lobe, with a concomitant decrease in arterial perfusion in the nonembolized lobe. PMID- 11766088 TI - Incidental parathyroid adenomas with normocalcemia discovered during thyroid operations: report of three cases. AB - We report three cases of parathyroid adenoma incidentally discovered during a total thyroidectomy. No patients showed any clinical or chemical features that led us to suspect a hyperparathyroidism condition before operation, but a macroscopically enlarged parathyroid was discovered during the dissection and it was removed in all three cases. All patients had a single adenoma confirmed by a histological analysis. Calcemia decreased after operation in every case but only one patient needed temporary adjunctive therapy. No permanent hypoparathyroidism or recurrent hyperparathyroidism was observed. We recommend that any enlarged parathyroid discovered during neck surgery should thus be removed in order to avoid the risks of future surgical procedures due to successive bouts of clinical hyperparathyroidism. PMID- 11766089 TI - Simultaneous minimally invasive direct coronary artery bypass and repair of a penetrating atherosclerotic ulcer of the descending thoracic aorta: report of a case. AB - A 70-year-old man with a descending aortic aneurysm was admitted to the hospital because of an abnormal chest X-ray. The chest computed tomography and magnetic resonance angiography findings showed a saccular aneurysm at the descending thoracic aorta. A preoperative coronary arteriogram showed 75% stenosis of the left anterior descending coronary artery and 99% stenosis of the right coronary artery. A simultaneous minimally invasive direct coronary artery bypass (MI PMID- 11766090 TI - Traumatized permanent teeth in Brazilian children assisted at the Federal University of Santa Catarina, Brazil. AB - The goal of this study was to determine factors related to the occurrence of dental trauma in permanent teeth of children assisted at the Pediatric Dentistry Clinic of the Federal University of Santa Catarina (UFSC) Florianopolis, Brazil. During a period of 18 months, 36 children between 7 and 12 years of age had 72 traumatized teeth treated. The children were all assisted by one professional, a dentist working as a trainee of the Pediatric Dentistry Clinic. The occurrence of trauma was higher in male patients (61.3%) and in children between 8 and 9 years old with an average age of mean=9.4 years. In the group assisted, 63.9% of the children had more than one traumatized tooth and trauma reoccurred 19.4% of the time. The maxillary anterior teeth represented 96.1% of the cases and the central incisor teeth were the most affected. Both sides of the mouth had approximately the same number of traumas. Fractures were more frequent (51.4%) than luxations (48.6%). Enamel/dentin crown fractures represented 51.4% of the total traumatized teeth. Falls were the main cause of trauma (83.3%). A dental professional assisted 36.1% of the children in some way during the first 24 h after the incident. The study concluded that the permanent dentition is mostly affected by crown fractures that occur especially on maxillary central incisor teeth in patients between 8 and 9 years of age. The major etiological factor is falls that affected more than one tooth. Re-occurrence of trauma is fairly common. PMID- 11766091 TI - A retrospective study of traumatic dental injuries in a Brazilian dental trauma clinic. AB - The purpose of this retrospective study was to analyse data from the records of patients seen in the dental trauma emergency clinic in a general hospital in the city of Recife, Brazil, during the years 1997-1999, according to sex, age, cause, number of injured teeth, type of tooth and type of trauma. The records of all patients seen by dentists were collected. Altogether, 250 patients from 1 to 59 years of age presenting 403 dental injuries were examined and/or treated. The causes of dento-alveolar trauma were classified in five categories: home injuries, street injuries, school injuries, sports activities, violence. The type of trauma was classified by dentists working at the dental trauma clinic on the basis of Andreasen's classification. The gender difference in the number of cases of trauma was statistically significant (males 63.2% vs females 36.8) (P<0.0001). Fracture in enamel only (51.6%) and fractures in dentine (40.8%) were the most commonly occurring types of injury. Injuries were most frequently diagnosed as serious among the youngest patients (up to 15 years of age); 82.4% of intrusive luxation cases were diagnosed in the 1-5 years age group. The main causes of tooth injury were falls (72.4%), collisions with objects (9.2%), violence (8.0%), traffic accidents (6.8%) and sports (3.6%). Trauma caused by violence was found to be statistically significant in the 6-15 years age group (P<0.0005). PMID- 11766092 TI - Periodontal response to two intracanal medicaments in replanted monkey incisors. AB - Intracanal medicaments are recommended for use in replanted teeth to inhibit inflammatory root resorption. This study compared the effect of calcium hydroxide (Pulpdent) and a corticosteroid-antibiotic paste (Ledermix) on periodontal healing and root resorption following replantation. Incisors of eight Macaca fascicularis monkeys were extracted, stored dry for 15 min and replanted. After 11 days, root canals in two adjacent maxillary incisors were treated with one medicament and contralateral incisors with the other medicament, or left as untreated controls. Animals were sacrificed 8 weeks later and the teeth prepared for histomorphometric evaluation of periodontal ligament inflammation and root resorption. Periodontal ligament inflammation and inflammatory root resorption were markedly inhibited by both calcium hydroxide and corticosteroid-antibiotic relative to untreated controls. Replacement resorption was lowest in the corticosteroid-antibiotic group, and significantly (P<0.05) more normal periodontal ligament was present in this group (79.6%) than in calcium hydroxide and control groups (64.6% and 62.7%, respectively). Treatment with the corticosteroid-antibiotic inhibited inflammatory resorption and was slightly more effective than calcium hydroxide in producing a periodontal healing response. PMID- 11766093 TI - Laboratory evaluation of mouthguard material. AB - The aim of this study was to evaluate, in vitro, the EVA material (polyvinylacetate-polyethylene copolymer) most commonly used in the fabrication of mouthguards and thus to help understand mouthguard performance and to improve mouthguard design. The material was tested for tensile strength, elongation, hardness and water absorption using specimens and tests described by the American Society for Testing and Materials Standards. Standard EVA sheets of 1, 2, 3 and 5 mm thickness were prepared. With increase in the thickness of the material, both the ultimate tensile strength and the elongation were decreased. The hardness and water absorption were unaffected. It was concluded that. overall, the thicker 5 mm EVA material was recommended for mouthguards as it displayed the least deformation to load and performed equally as well in the tests as other thicknesses. PMID- 11766094 TI - Comparison of a new dental trauma splint device (TTS) with three commonly used splinting techniques. AB - Splinting is the standard of care for stabilization of replanted or repositioned permanent teeth following trauma. The present experimental study compared four dental trauma splints in 10 volunteers. The evaluated splints included a wire composite splint (WCS), a button-bracket splint (BS), a resin splint (RS), and a new device (TTS=Titanium Trauma Splint) specifically developed for splinting traumatized teeth. All splints were bonded to the labial surfaces of the maxillary lateral and central incisors. Splints were left in place for 1 week. After splint removal, the next splint was placed after a 1-week rest period. The sequence of splint application was randomized for each individual. The following parameters were assessed: tooth mobility with horizontal and vertical Periotest values (PTV) before and after splint application and splint removal, respectively; probing depths, plaque and bleeding on probing indices before splint application and removal, and chair time needed for splint application and removal. After splint application, horizontal PTV were significantly lower in central incisors for BS compared to TTS (P=0.04), and for RS compared to TTS (P=0.005) and to WCS (P=0.006). Reduction of lateral tooth mobility (=splint effect) expressed by the difference between horizontal pre- and postoperative PTV was significantly greater in RS compared to TTS and WCS (P<0.05) for central as well as for lateral incisors. However, changes of vertical tooth mobility were not significant across the splinting techniques. Periodontal parameters remained unchanged, reflecting the excellent oral hygiene by the study subjects. The chair time needed for splint application was significantly shorter for TTS (P<0.01). In conclusion, all tested splints appeared to maintain physiologic vertical and horizontal tooth mobility. However, the latter was critically reduced in RS splints. PMID- 11766095 TI - Different treatment outcomes of two intruded permanent incisors--a case report. AB - Intrusive luxation involves the displacement of the tooth apically into the alveolar socket. This type of injury represents a very complex wound, involving disruption of the marginal gingival seal, alveolar bone, periodontal ligament fibers, cementum and the neuro-vascular supply to the pulp, which results in severely compromised healing and possible complications. The case presented is a report of a 60-year-old lady who fell and intruded her two maxillary central incisors. The healing outcomes of the two central incisors were markedly different from each other even though they sustained similar injuries. PMID- 11766096 TI - Epidemiological data of cryptococcosis in Austria, Germany and Switzerland: part of the ECMM survey in Europe. European Confederation of Medical Mycology. AB - The data raised for Cryptococcus neoformans and cryptococcosis in Austria, Germany and Switzerland during the period from July 1997 to December 1999 are presented and analysed according to the epidemiological criteria. This is part of the ECMM survey in Europe. PMID- 11766097 TI - Congress report. Aspergillus fumigatus--virulence and opportunism? PMID- 11766098 TI - Aspergillus detection in bronchoscopically acquired material. Significance and interpretation. AB - Pulmonary invasive aspergillosis is frequently difficult to diagnose. In particular, the value of the cultivation of Aspergillus and the Aspergillus galactomannan antigen detection (Pastorex) in bronchoscopically acquired material (bronchoalveolar lavage = BAL, bronchial lavage = BL) in the course of diagnosing this mycosis is viewed controversially. Between January 1996 and September 1999, we obtained 114 positive results in 100 bronchoscopically aquired specimens from a total of 69 patients. 59 of the 69 patients were immunosuppressed, 42 suffered from pulmonary aspergillosis and 38 suffered from invasive pulmonary aspergillosis. The positive prediction rate for a positive result with regard to pulmonary aspergillosis in bronchoscopically acquired material was approximately 61%. Cultivation of Aspergillus was more successful in BAL, and the Aspergillus antigen detection was more successful in BL. PMID- 11766099 TI - Phospholipases of Candida albicans. AB - Infections due to Candida albicans are frequent and of clinical importance. Especially at a time of increasing organ transplantations, HIV infections, and resistance to antimicrobial agents a profound knowledge of the interaction between C. albicans and host tissue is mandatory. In addition to secreted aspartyl proteinase, dimorphism, cell surface composition, and toxin production phospholipases are a main factor in pathogenicity. Up to the present, many different groups and subgroups of phospholipases have been detected. These different enzymes are related to various types of aggressive and defensive actions. These range from active invasion of host cell tissue to growth control and remodelling of the yeast cell membrane. It is clear that a multiplicity of factors must co-operate to overcome the host's defences. Yet it can be supposed today that phospholipases are one important factor in this complex interaction. Therefore the known phospholipases of C. albicans are described in detail under clinical aspects. PMID- 11766100 TI - Extrusion of fluorescein diacetate by multidrug-resistant Candida albicans. AB - Over-expression of multidrug efflux transporters causes Candida albicans cells to be resistant to azole antifungal agents. There are several kinds of indicator for multidrug resistance (MDR) phenotype of higher eukaryotic cells. Calcein AM is a prefluorochrome that is known as a substrate for multidrug efflux transporters of mammalian cells. We investigated whether calcein AM was also extruded by the ATP dependent multidrug transporter (cdr1p) of C. albicans. There was no significant difference in the accumulation of calcein AM between MDR cells and drug susceptible cells of C. albicans even with sodium azide, suggesting that calcein AM may not be associated with the CDR1-gene-related multidrug efflux system of C. albicans. However, a structurally related prefluorochrome derivative, fluorescein diacetate (FDA), was shown to be extruded by the CDR1 mRNA-overexpressing yeast cells. In comparison with drug-susceptible cells, the resistant cells emitted very weak fluorescence when stained with FDA. Furthermore sodium azide increased the fluorescence of the resistant cells more than 20 times, whereas the fluorescence in the drug-susceptible cells with FDA and sodium azide was three to four times stronger. These results suggested that FDA might be extruded by the CDR1-related multidrug efflux transporter of C. albicans. PMID- 11766101 TI - Antifungal activity of propolis on different species of Candida. AB - Propolis is a resinous material collected by bees from the buds or other parts of plants. It is known for its biological properties, having antibacterial, antifungal and healing properties. The antifungal activity of propolis was studied in sensitivity tests on 80 strains of Candida yeasts: 20 strains of Candida albicans, 20 strains of Candida tropicalis, 20 strains of Candida krusei and 15 strains of Candida guilliermondii. The yeasts showed a clear antifungal activity with the following order of sensitivity: C. albicans > C. tropicalis > C. krusei > C. guilliermondii. Patients with full dentures who used a hydroalcoholic propolis extract showed a decrease in the number of Candida. PMID- 11766102 TI - Search for correlation between symptoms and signs of changes in the oral mucosa and presence of fungi. AB - The aim of the present study was to determine the relationship between the symptoms and signs of oral mucosal changes and the presence of fungi. The investigation comprised 235 subjects. Fungi were detected in the oral cavities of 196 of these subjects. The fungi belonged to different species of the genus Candida. A significant correlation was found between the presence of fungi in the oral cavity and the existence of burning sensation, xerostomia, dysgeusia and non idiopathic bleeding from the surface of the oral mucosa. A similar correlation was observed between the fungal colonization and atrophic changes, as well as reddened oral mucosa with lesions, ulceration and keratotic problems. PMID- 11766103 TI - Characterization of Aphanomyces invadans isolates using pyrolysis mass spectrometry (PyMS). AB - Twenty-one isolates of Aphanomyces invadans, the fungal pathogen associated with the Asian fish disease epizootic ulcerative syndrome (EUS), were compared with other Oomycete fungi in terms of their pyrolysis mass spectrometry (PvMS) profiles. Canonical variate analysis (CVA) of the pyrolysis mass spectra distinguished the Aphanomyces species from a wide scatter of Achlya and Saprolegnia isolates. Further CVA and hierarchal cluster analysis (HCA) separated the Aphanomyces species into two main groups. The first group clustered A. invadans isolates from EUS outbreaks in Thailand, Bangladesh, Indonesia, Philippines, Australia and Japan together. However, HCA also included the crayfish plague fungus Aphanomyces astaci within this group. Non-pathogenic Aphanomyces strains isolated from ulcerative mycosis (UM)-affected fish were shown to be distinct from A. invadans, and instead clustered with saprophytic Aphanomyces strains to form the second group. Recently, an invasive Aphanomyces pathogen has been isolated from UNI-affected fish, but that was not tested here. This is the first report using PyMS in the study of Oomycete systematics. The technique was not sensitive enough to show any intraspecific differences, but it was considered a useful technique for the discrimination of species where taxonomic relationships are uncertain. PMID- 11766104 TI - Mites in fungal cultures. AB - Recently all existing Trichophyton mentagrophytes colonies within our laboratory, which had originally appeared normal, rapidly and at an early stage became perforated. Therefore the aims of this study were to expose the cause of these major morphological changes and to find out if this phenomenon may occur in other fungal cultures. Microscopic examination of specimens taken from the damaged colonies showed many mites at different developmental stages, which were subsequently identified as the acarus, Tyrophagus putrescentiae. The laboratory experiments demonstrated that mites feed on the spores and hyphae of all the dermatophytes, moulds and yeasts tested. For the time being Tyrophagus putrescentiae is an unpleasant pest which damages fungal cultures but future use of the acari in biological control may be considered. PMID- 11766105 TI - Otomycosis in Nigeria: treatment with mercurochrome. AB - Seventy-two mycologically proven cases of otomycosis (38 males, 34 females) aged 8-80 years were investigated. Aspergillus niger was the commonest aetiological agent (43.1%) followed by Candida spp. (22.2%), A. flavus (19.4%) and A. fumigatus (15.3%). Three topical drugs, namely mercurochrome, clotrimazole and locacorten-vioform, were evaluated for otomycosis therapy in separate groups of 24 patients each. Mercurochrome was found to be the most efficacious in terms of healing, relief from symptoms of the disease and production of negative fungal cultures. Mercurochrome is recommended as a safe and economical drug for the topical treatment of otomycosis in developing countries like Nigeria. PMID- 11766106 TI - Tinea capitis in adults during 1981-95 in northern Greece. AB - The mycological laboratory of our Hospital examined 31,073 patients between 1981 and 1995. Sex, age, the residence of patients, the clinical type of tinea and contacts with other persons and animals were investigated. All the patients were also examined under Wood's light. Tinea capitis was diagnosed in 35 adults. Trichophyton violaceum was the commonest aetiological agent (54.5%), especially in elderly women. The other anthropophilic fungi were T. rubrum (8.5%), T. schoenleinii (5.7%) and T. tonsurans (2.8%). The zoophilic fungi Microsporum canis (14.3%), T. terrucosum (8.5%) and T. mentagrophytes (5.7%) were also isolated. PMID- 11766107 TI - Airborne viable fungi in Riyadh and allergenic response of their extracts. AB - The allergenicity and antigenicity of various airborne fungi isolated from the atmosphere of Riyadh were studied. Protein nitrogen contents were estimated and found to range from 0.9 mg ml(-1) for Cladosporium to 2.1 mg ml for Aspergillus extracts. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis for those extracts exhibited a number of protein bands of higher molecular weight between 13 and 80 kDa for Alternaria, Ulocladium, Penicillium, Aspergillus and Cladosporium. Extracts in both aqueous and lyophilized forms were sterilized and tested for diagnostic skin prick test in 100 consecutive patients having bronchial asthma and allergic rhinitis. Overall, 13% of patients reacted positively to fungal extracts, revealing allergic sensitization to these fungi. These findings necessitate further investigation as regards the purification and characterization of these local extracts for better diagnostic use in patients in Saudi Arabia. PMID- 11766108 TI - Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis. AB - A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis. PMID- 11766109 TI - Case report. Hepatic abscesses due to Aspergillus terreus in an immunodeficient child. AB - We report the first case of hepatitis due to Aspergillus terreus in a 13-year-old boy with common variable immunodeficiency that occurred while the patient was receiving secondary prophylaxis with fluconazole after an episode of pulmonary candidosis. The infection subsided after the addition of itraconazole to the combination of liposomal amphotericin B and granulocyte-macrophage colony stimulating factor that he was receiving. PMID- 11766110 TI - Case report. Cutaneous cryptococcosis in a patient with systemic erythematous lupus. AB - The first case of a cutaneous cryptococcosis associated with systemic erythematous lupus (SLE) diagnosed in our Mycology Reference Centre is presented: a 24-year-old female patient diagnosed with SLE, nephrotic syndrome, arterial hypertension, renal insufficiency due to glomerulonephritis type IV and cellulitis in the right thigh and gluteus. Cryptococcus neoformans was isolated by cutaneous biopsy and haemoculture. Cryptococcal antigen was detected in serum by the latex agglutination test. As the patient did not respond to fluconazol intravenous treatment, amphotericin B administration was performed. She died of acute renal insufficiency. PMID- 11766111 TI - Case report. Successful treatment of two cases of post-surgical sternal osteomyelitis, due to Candida krusei and Candida albicans, respectively, with high doses of triazoles (fluconazole, itraconazole). AB - Two female patients, aged 75 and 59 years, respectively, with candidal sternal osteomyelitis were successfully treated by the administration of triazoles. Both had developed post-operative wound infection after sternotomy for coronary artery by-pass grafting. Sternal osteomyelitis was confirmed by bone scans with technetium 99Tc and gallium 67Ga. The cultures, from the pus draining at the site of the sternotomy scar, grew Candida krusei in the first case. The fistula closed after a 9-week course of itraconazole therapy (800 mg daily, followed by 600 mg daily) and the patient completed a 6-month period of therapy. The second patient had underlying diabetes mellitus. Post-operatively she developed two fistulae draining pus on the sternum. The pus cultures grew C. albicans. Initial treatment with oral fluconazole (400 mg daily) failed. Subsequent treatment with liposomal amphotericin B also failed. A dramatic improvement was noted when the patient received high doses of fluconazole (800 mg daily). The fistulae gradually closed after 1 month. Oral fluconazole was continued for 6 months. The cure was confirmed by bone scans. Three years later, both patients remained well. PMID- 11766112 TI - Case report. Trichophyton mentagrophytes var. nodulare causing tinea pedis. AB - The identification of Trichophyton mentagrophytes var. nodulare is described, based on a strain recently isolated from tinea pedis. Different culture media and physiological tests were used in order to compare this strain with related strains. The main characteristics of T. mentagrophytes var. nodulare were its deep yellow-orange pigmentation, which was released from the mycelium, the flat growth of its colonies and the formation of nodular bodies. Supplementation of Sabouraud glucose agar with 3% NaCl reduced the aerial mycelium and stimulated the formation of conidia. Until now an identification of T. mentagrophytes var. nodulare based on DNA-patterns has not been published. Trichophyton mentagrophytes var. nodulare is supposed to be an anthropophilic dermatophyte causing ordinary tinea and onychomycosis. The low number of reports indicates that it is a very rare variety. PMID- 11766113 TI - Antifungal activity of the new azole UK-109 496 (voriconazole): addition and clarification. PMID- 11766114 TI - Light in the distance. PMID- 11766115 TI - Botanical briefs: The cashew tree--Anacardium occidentale L. PMID- 11766116 TI - Photo quiz. Preauricular pit. PMID- 11766117 TI - Inflammatory linear verrucous epidermal nevus. AB - Inflammatory linear verrucous epidermal nevus (ILVEN) is an unusual unilateral eruption with onset usually in infancy or childhood, female predominance, frequent left leg involvement, pruritus, refractoriness to therapy, and a psoriasiform histologic pattern. We review this disorder in describing a 5-year old girl who also had melanodontia, an association not previously observed to our knowledge. PMID- 11766118 TI - Biologic therapy for psoriasis: a brief history, I. AB - This article, the first in a 2-part series, reviews the treatment of psoriasis with biologic therapy. Although extensive research in this venue of treatment is currently being conducted, we review some of the pioneering clinical trials dealing with immunotherapy, including the use of peptide T, anti-CD4 antibody (OKTcdr4a and hIgG1-CD4), and anti-Tac. For each of these therapies, an extensive summation is given of the research, taking note of the investigators' procedural course, results, and side effects seen. Through the results of these studies, a foundation was laid for the further exploration of the use of biologic therapy to combat psoriasis. PMID- 11766119 TI - Psoriasis in infancy: therapy with calcipotriene ointment. AB - Psoriasis in infancy is often more therapeutically challenging than atopic and seborrheic dermatitis. The generalized nature of psoriasis and the intensity of inflammation often reduce the efficacy of topical corticosteroids. Furthermore, involvement of intertriginous skin and the presence of scalp disease limit the potency of the topical steroids that can be prescribed. We report on an infant treated with topical calcipotriene for infantile psoriasis who experienced greater benefit than he had with standard corticosteroid medications. Laboratory testing for calcium metabolism was normal during the course of therapy. We conclude that calcipotriene can be a safe and effective therapy for psoriasis in early infancy. PMID- 11766120 TI - Narrowband UVB phototherapy for the treatment of psoriasis: a review and update. AB - An advance in UVB-based phototherapy has been the introduction of fluorescent lightbulbs (Philips TL-01) that deliver monochromatic light at 311-nm UVB, a narrowband wavelength that seems to maximize clearing of plaques relative to its erythrogenic potential. Narrowband UVB phototherapy has considerable advantages over traditional treatment options such as broadband UVB and psoralen plus UVA (PUVA). It is clearly more effective than broadband UVB, safer than PUVA, and well tolerated by patients when taken at suberythemogenic doses. Narrowband UVB represents an important new therapy for psoriasis. PMID- 11766121 TI - A review of the 308-nm excimer laser in the treatment of psoriasis. AB - The 308-nm excimer laser is a new modality for the treatment of psoriasis. With the 308-nm UVB radiation generated by this laser, it is possible to clear psoriasis with as little as one treatment and to have a moderately long remission. In contrast to traditional phototherapy techniques, this handheld excimer laser UVB therapy is selectively directed toward lesional skin, thus sparing the surrounding normal skin from unnecessary radiation exposure. This modality may offer a new alternative in the treatment of limited psoriasis and other inflammatory diseases. PMID- 11766122 TI - Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study. AB - A double-blind, randomized, vehicle-controlled, parallel-group trial was performed to compare the efficacy and tolerability of tazarotene 0.1% gel and vehicle gel in 31 patients with fingernail psoriasis. Patients were randomized to receive tazarotene or vehicle gel, which they applied each evening for up to 24 weeks to 2 target fingernails, one under occlusion and one unoccluded. The tazarotene treatment resulted in a significantly greater reduction in onycholysis in occluded nails (P < or = .05 at weeks 4 and 12) and a significantly greater reduction in onycholysis in nonoccluded nails (P < or = .05 at week 24). Tazarotene also resulted in a significantly greater reduction in pitting in occluded nails (P < or = .05 at week 24). There were no other significant between group differences in pitting, subungual hyperkeratosis, leukonychia, nail plate crumbling/loss, splinter hemorrhage, or nail growth rate. Tazarotene 0.1% gel was well tolerated with only 5 of the 21 tazarotene-treated patients reporting a treatment-related adverse event (all mild or moderate). In conclusion, tazarotene 0.1% gel can significantly reduce onycholysis (in occluded and nonoccluded nails) and pitting (in occluded nails) and is well tolerated in the treatment of nail psoriasis. PMID- 11766124 TI - A subchronic toxicity study of Phosflex 51B in Sprague-Dawley rats. AB - Phosflex 51B is a flame retardant plasticizer that is blended with polyvinyl chloride films to effectively control product flammability. Its composition places it in the butylated triphenyl phosphate category. Previous studies have shown Phosflex 51B to have low acute toxicity, to lack teratogenic and mutagenic activity, and to not induce delayed peripheral neuropathy. The present study was conducted to determine the toxicity of Phosflex 51B after repeated dietary exposure. Four groups, each consisting of 20 male and 20 female Sprague-Dawley rats, received rodent diet containing either 0, 100, 400, or 1600 ppm for 90 days. Parameters measured include body weight, food consumption, clinical observations, hematology, clinical chemistry, and cholinesterase activity. Tissues were examined at necropsy for gross changes and were processed for microscopic pathology. There were no significant treatment-related effects on body weights, food consumption, hematology and clinical chemistry, or cholinesterase values. A significant increase was observed in the absolute and relative mean weights of livers in high-dose male rats, the mean relative liver weights of the high-dose female animals, the mean relative kidney weights of the high-dose male rats, and the mean absolute weights of the adrenal glands from high-dose female rats. Neither gross nor microscopic pathology examinations revealed tissue changes in these organs or in any other organs. Although increases in liver, kidney, and adrenal weights were observed in certain animals in the 1600-ppm high-dose group, the administration of Phosflex 51B did not result in significant treatment-related adverse effects at dietary dose levels of 100 and 400 ppm. The no-observable-effect level (NOEL) in this study is 400 ppm. PMID- 11766123 TI - Trichloroethylene, trichloroacetic acid, and dichloroacetic acid: do they affect fetal rat heart development? AB - Trichloroethylene (TCE), trichloroacetic acid (TCA), and dichloroacetic acid (DCA) are commonly found as groundwater contaminants in many regions of the United States. Cardiac birth defects in children have been associated with TCE, and laboratory studies with rodents report an increased incidence of fetal cardiac malformations resulting from maternal exposures to TCE, TCA, and DCA. The objective of this study was to orally treat pregnant CDR(CD) Sprague-Dawley rats with large bolus doses of either TCE (500 mg/kg), TCA (300 mg/kg), or DCA (300 mg/kg) once per day on days 6 through 15 of gestation to determine the effectiveness of these materials to induce cardiac defects in the fetus. All trans retinoic acid (RA) dissolved in soybean oil was used as a positive control. Soybean oil is commonly used as a dosing vehicle for RA teratology studies and was also used in this study as a dosing vehicle for TCE. Water was used as the dosing vehicle for TCA and DCA. Fetal hearts were examined on gestation day (GD) 21 by an initial in situ, cardiovascular stereomicroscope examination, and then followed by a microscopic dissection and examination of the formalin-fixed heart. The doses selected for TCA and DCA resulted in a modest decrease in maternal weight gain during gestation (3% to 8%). The fetal weights on GD 21 in the TCA and DCA treatment groups were decreased 8% and 9%, respectively, compared to the water control group and 21% in the RA treatment group compared to soybean oil control group. The heart malformation incidence for fetuses from the TCE-, TCA-, and DCA-treated dams did not differ from control values on a per fetus or per litter basis. The rate of heart malformations, on a per fetus basis, ranged from 3% to 5% for TCE, TCA, and DCA treatment groups compared to 6.5% and 2.9% for soybean oil and water control groups. The RA treatment group was significantly higher with 33% of the fetuses displaying heart defects. For TCE, TCA, and DCA treatment groups 42% to 60% of the litters contained at least one fetus with a heart malformation, compared to 52% and 37% of the litters in the soybean oil and water control groups. For the RA treatment group, 11 of 12 litters contained at least one fetus with a heart malformation. Further research is needed to quantify the spontaneous rates of heart defects for vehicle control rats and to explain the disparity between findings in the present study and other reported findings on the fetal cardiac teratogenicity of TCE, TCA, and DCA. PMID- 11766126 TI - The role of interleukin-6 (IL-6) in human sulfur mustard (HD) toxicology. AB - The authors applied in vitro models of controlled damage to human epidermal keratinocytes (HEKs), human skin fibroblasts (HSFs), and human breast skin tissue (HBST) to examine the mechanism responsible for sulfur mustard (HD)-induced interleukin-6 (IL-6) alterations. Treatment with 100 microM HD for 24 hours resulted in a significant increased amount of IL-6 being secreted by HEKs (HD exposed to control ratio [E/C] = 4.15 +/- 0.07) and by HSFs (E/C = 7.66 +/- 0.04). Furthermore, the HD-induced secretion of IL-6 in HEKs was neutralized with monoclonal human IL-6 antibodies. The secretion of IL-6 in HBST supernatant exposed to HD produced conflicting results. Although an increase of IL-6 was observed in control superfusion media from HBST, IL-6 levels were observed to decrease as the concentration of HD increased. Time course of IL-6 mRNA levels were performed using a competitive polymerase chain reaction (PCR) and human IL-6 mRNA assay detection kit in control and HD (100 microM)-treated HEKs cells. IL-6 mRNA transcripts in HD-exposed HEKs were first observed within 2 hours, dropped at 5 to 6 hours, and increased by approximately 2.2-fold and 8.5-fold at 24 to 48 hours after HD exposure, respectively, as detected by the Xplore mRNA Quantification System. Surface-enhanced laser desorption ionization (SELDI) mass spectrometry was also applied to study the secretion pattern of IL-6 on lysate preparations of HBST. A peak in the area of 23,194 to 23,226 Da was detected using antibody coupled to the chip. This peak was assigned to correspond to the mass of the IL-6 glycoprotein. Recombinant human IL-6 (rhIL-6) exposed to HD lacked the second disulfide bridge and was partially unfolded, as determined by nuclear magnetic resonance-nuclear Overhauser enhancement and exchange spectroscopy (NMR-NOESY). The disappearance of the resonance peak at 3.54 ppm and the appearance of a new chemical shift at 1.85 ppm suggested that a change in structure had occurred in the presence of HD. From the data, the possibility cannot be excluded that IL-6 might be involved in the early event of structural changes of the signal transducer glycoprotein that indirectly initiates the cascade of events such as skin irritation and blister formation observed in the pathophysiology of HD injury. PMID- 11766125 TI - Effects of manganese on inositol polyphosphate receptors and nitric oxide synthase activity in rat brain. AB - The neurotoxic effects of excessive exposure to manganese (Mn) include degeneration of dopaminergic neurons, impairment of energy metabolism, and perturbations in phosphoinositide (PI) hydrolysis leading to altered calcium (Ca2+) homeostasis. This study is designed to assess the in vitro and in vivo effects of Mn on Ca2+/calmodulin-dependent neuronal nitric oxide synthase (nNOS) activity and on the regulation of inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4) receptors involved in intracellular and extracellular mobilization of Ca2+. In vivo Mn exposure significantly increased 3H-InsP3 and 3H-InsP4 binding in the cerebellum and the cerebral cortex in a dose-dependent manner. However, in vitro Mn decreased 3H-InsP3 binding and increased 3H-InsP4 binding. In vitro and in vivo exposure of Mn inhibited nNOS activity in the cerebellum and the cerebral cortex. Immunohistochemical studies also showed a notable decrease in nNOS immunoreactivity in the granule cell layer of the cerebellum, whereas no significant changes were observed in the cerebral cortex. These data suggest that Mn neurotoxicity may be due to altered calcium homeostasis by its modulation of inositol polyphosphate receptors. Further, the inhibition of nNOS by Mn is of considerable importance because NO regulates a number of neurotransmitter functions. PMID- 11766128 TI - Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic cracked naphtha distillate in rats. AB - A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm. PMID- 11766127 TI - Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats. AB - Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote. PMID- 11766129 TI - Differential diagnosis of byssinosis by blood histamine and pulmonary function test: a review and an appraisal. AB - A study was conducted on byssinotic (N = 8) and nonbyssinotic (N = 16) mill workers exposed to cotton dust and on controls (N = 15) from a cotton dust-free zone. They were examined for chest tightness and breathlessness during successive days from Mondays to Fridays. In addition to monitoring the workers only on Mondays after shift work, their blood histamine levels and pulmonary function tests such as FEV1, PEFR, and FEF25-75% (PEFR represents airflow of larger airways, FEF25-75% reflects airflow in smaller airways, and FEV1 represents airflow in both central and peripheral airways) were screened, but Monday data were only counted to appraise a contrast between these two parameters. The results showed that the histamine levels were significantly higher in the cotton dust-exposed workers in association with significantly decreased FEV1, PEFR, and FEF25-75%, indicating bronchoconstriction of the central, larger, and peripheral airways. Histamine can cause a severe constriction of the central as well as peripheral airways in cotton dust-exposed workers, enabling a paradoxical effect for a differential diagnosis of byssinosis. PMID- 11766130 TI - Final report on the safety assessment of Acid Violet 43. AB - Acid Violet 43 is an anthraquinone color that may be used as a colorant in cosmetic formulations that are hair dyes, colors, and coloring rinses. Batches of Acid Violet 43 that are certified to meet the United States Food and Drug Administration (U.S. FDA) specifications are termed Ext. D & C Violet No. 2. Hair dyes and colors containing Acid Violet 43 are considered coal tar ingredients and, as such, routinely bear a caution statement regarding potential skin irritation and instructions for determining whether the product causes skin irritation in any given individual. Expected concentrations of use are less than or equal to 1%. Impurities include anthracenedione derivatives, p-toluidine, and p-toluidine sulfonic acid, as well as heavy metals. Based on extensive safety test data, the U.S. FDA has established specifications (including limits on impurities) for Ext. D & C Violet No. 2 that allow its use in any cosmetic. It is the certified color (Ext. D & C Violet No. 2) that has been evaluated in the following safety tests. Oral toxicity tests do not demonstrate significant acute toxicity. In a short-term dermal toxicity study using guinea pigs and a subchronic dermal toxicity study using rabbits, no signs of systemic toxicity and no significant local skin reactions were noted. This ingredient was not genotoxic in bacterial assays, nor was it carcinogenic when applied to mouse skin at a 1% concentration. Accordingly, Acid Violet 43 was determined to be safe for use in hair dye formulations, when impurities are limited as follows: < or = 18% volatile matter (at 135 degrees C) and chlorides and sulfates (calculated as sodium salts); < or = 0.4% water-insoluble matter; < or = 0.2% 1-hydroxy-9,10 anthracenedione; < or = 0.2% 1,4-dihydroxy-9,10-anthracenedione; < or = 0.1% p toluidine; < or = 0.2% p-toluidine sulfonic acids, sodium salts; < or = 1% subsidiary colors; < or = 20 ppm lead (as Pb); < or = 3 ppm arsenic (as As); < or = 1 ppm mercury (as Hg); and with > or = 80% total color. PMID- 11766131 TI - Final report on the safety assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. AB - Benzyl Alcohol is an aromatic alcohol used in a wide variety of cosmetic formulations as a fragrance component, preservative, solvent, and viscosity decreasing agent. Benzoic Acid is an aromatic acid used in a wide variety of cosmetics as a pH adjuster and preservative. Sodium Benzoate is the sodium salt of Benzoic Acid used as a preservative, also in a wide range of cosmetic product types. Benzyl Alcohol is metabolized to Benzoic Acid, which reacts with glycine and excreted as hippuric acid in the human body. Acceptable daily intakes were established by the World Health Organization at 5 mg/kg for Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Benzoic Acid and Sodium Benzoate are generally recognized as safe in foods according to the U.S. Food and Drug Administration. No adverse effects of Benzyl Alcohol were seen in chronic exposure animal studies using rats and mice. Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth. Some differences between control and Benzyl Alcohol-treated populations were noted in one reproductive toxicity study using mice, but these were limited to lower maternal body weights and decreased mean litter weights. Another study also noted that fetal weight was decreased compared to controls, but a third study showed no differences between control and Benzyl Alcohol-treated groups. Benzoic Acid was associated with an increased number of resorptions and malformations in hamsters, but there were no reproductive or developmental toxicty findings in studies using mice and rats exposed to Sodium Benzoate, and, likewise, Benzoic Acid was negative in two rat studies. Genotoxicity tests for these ingredients were mostly negative, but there were some assays that were positive. Carcinogenicity studies, however, were negative. Clinical data indicated that these ingredients can produce nonimmunologic contact urticaria and nonimmunologic immediate contact reactions, characterized by the appearance of wheals, erythema, and pruritus. In one study, 5% Benzyl Alcohol elicited a reaction, and in another study, 2% Benzoic Acid did likewise. Benzyl Alcohol, however, was not a sensitizer at 10%, nor was Benzoic Acid a sensitizer at 2%. Recognizing that the nonimmunologic reactions are strictly cutaneous, likely involving a cholinergic mechanism, it was concluded that these ingredients could be used safely at concentrations up to 5%, but that manufacturers should consider the nonimmunologic phenomena when using these ingredients in cosmetic formulations designed for infants and children. Additionally, Benzyl Alcohol was considered safe up to 10% for use in hair dyes. The limited body exposure, the duration of use, and the frequency of use were considered in concluding that the nonimmunologic reactions would not be a concern. Because of the wide variety of product types in which these ingredients may be used, it is likely that inhalation may be a route of exposure. The available safety tests are not considered sufficient to support the safety of these ingredients in formulations where inhalation is a route of exposure. Inhalation toxicity data are needed to complete the safety assessment of these ingredients where inhalation can occur. PMID- 11766132 TI - Final report on the safety assessment of Octyidodecyl Stearoyl Stearate. AB - Octyldodecyl Stearoyl Stearate functions as an occlusive skin-conditioning agent and as a nonaqueous viscosity-increasing agent in many cosmetic formulations. Current concentrations of use are between 0.7% and 23%, although historically higher concentrations were used. The chemical is formed by a high-temperature, acid-catalyzed esterification reaction of long-chain alcohols (primarily C-20) and a mixture of primarily C-18 fatty acids. Levels of stearic acid, octyldodecanol, and octylydocecyl hydroxystearate in the final product are 5% or less--no other residual compounds are reported. Only limited safety test data were available on Octyldodecyl Stearoyl Stearate, but previous safety assessments of long-chain alcohols and fatty acids found these precursors to be safe for use in cosmetic formulations. Octyldodecyl Stearoyl Stearate produced no adverse effects in acute exposures in rats. The chemical was mostly nonirritating to animal skin at concentrations ranging from 7.5% to 10%; one study did find moderate irritation in rabbit skin at a concentration of 7.5%. Clinical tests at a concentration of 10.4% confirmed the absence of significant irritation in humans. An ocular toxicity study in rabbits found no toxicity. No evidence of genotoxicity was found in either a mammalian test system or in the Ames test system, with or without metabolic activation. The available data on Octyldodecyl Stearoyl Stearate and the previously considered data on long-chain alcohols and fatty acids, however, did not provide a sufficient basis to make a determination of safety. Additional data needs include (1) chemical properties, including the octanol/water partition coefficient; and (2) if there is significant dermal absorption or if significant quantities of the ingredient may contact mucous membranes or be ingested, then reproductive and developmental toxicity data may be needed. Until such time as these data are received, the available data do not support the safety of Octyldodecyl Stearoyl Stearate as used in cosmetic formulations. PMID- 11766133 TI - Final report on the safety assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water. AB - Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, Mentha Piperita (Peppermint) Leaf Water are obtained from the Mentha piperita plant. The oil is currently used in cosmetic formulations as a fragrance component, but previously had been also described as a denaturant. The extract and leaves are described as biological additives, but only the extract is reported to be used. Peppermint Water is described as a flavoring agent or fragrance component, but is not currently in use. Peppermint Oil is used at a concentration of < or = 3% in rinse-off formulations and < or = 0.2% in leave-on formulations. Peppermint Oil is composed primarily of menthol and menthone. Other possible constituents include pulegone, menthofuran, and limone. Most of the safety test data concern Peppermint Oil. The oil is considered to present the "worst case scenario" because of its many constituents, so data on the oil were considered relevant to the entire group of ingredients. Peppermint Oil was minimally toxic in acute oral studies. Short-term and sub chronic oral studies reported cystlike lesions in the cerebellum in rats that were given doses of Peppermint Oil containing pulegone, pulegone alone, or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognized hepatotoxin. Repeated intradermal dosing with Peppermint Oil produced moderate and severe reactions in rabbits, although Peppermint Oil did not appear to be phototoxic. Peppermint Oil was negative in the Ames test and a mouse lymphoma mutagenesis assay but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. In a carcinogenicity study of toothpaste and its components, no apparent differences were noted between mice treated with Peppermint Oil and those treated with the toothpaste base. Isolated clinical cases of irritation and/or sensitization to Peppermint Oil and/or its constituents have been reported, but Peppermint Oil (8%) was not a sensitizer when tested using a maximization protocol. It was expected that dermal absorption of Peppermint Oil would be rapid, following that of menthol, a major component, but in no case would be greater than absorption through the gastrointestinal tract. Because of the toxicity of pulegone, the safe concentration of this constituent was limited to < or = 1%. This concentration was achievable both by controlling the time of harvest and processing technique. There is evidence that menthol can enhance penetration of other agents. Formulators were cautioned that this enhanced penetration can affect the use of other ingredients whose safety assessment was based on their lack of absorption. With the limitation that the concentration of pulegone in these ingredients should not exceed 1%, it was concluded that Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Extract, Mentha Piperita (Peppermint) Leaves, Mentha Piperita (Peppermint) Water are safe as used in cosmetic formulations. PMID- 11766134 TI - Final report on the safety assessment of Ammonium, Potassium, and Sodium Persulfate. AB - Ammonium, Potassium, and Sodium Persulfate are inorganic salts used as oxidizing agents in hair bleaches and hair-coloring preparations. Persulfates are contained in hair lighteners at concentrations up to 60%, in bleaches and lighteners at up to 22% and 16%, respectively, and in off-the-scalp products used to highlight hair strands at up to 25%. They are used in professional product bleaches and lighteners at similar concentrations. Much of the available safety test data are for Ammonium Persulfate, but these data are considered applicable to the other salts as well. Acute dermal, oral, and inhalation toxicity studies are available, but only the latter are remarkable, with gross lesions observed in the lungs, liver, stomach, and spleen. In short-term and subchronic feeding studies the results were mixed; some studies found no evidence of toxicity and others found local damage to the mucous membrane in the gastrointestinal tract, but no other systemic effects. Short-term inhalation toxicity was observed when rats were exposed to aerosolized Ammonium Persulfate at concentrations of 4 mg/m3 and greater. Ammonium Persulfate (as a moistened powder) was not an irritant to intact rabbit skin, but was sensitizing (in a saline solution) to the guinea pig. It was slightly irritating to rabbit eyes. Ammonium Persulfate was negative in the Ames test and the chromosomal aberration test. No significant evidence of tumor promotion or carcinogenicity was observed in studies of rats receiving topical applications of Ammonium Persulfate. The persulfates were reported to cause both delayed-type and immediate skin reactions, including irritant dermatitis, allergic eczematous dermatitis, localized contact urticaria, generalized urticaria, rhinitis, asthma, and syncope. The most common causes of allergic dermatitis in hairdressers are the active ingredients in hair dyes, and Ammonium Persulfate has been identified as a frequent allergen. A sensitization study that also examined the incidence of urticarial reactions was performed with 17.5% Ammonium, Potassium, and Sodium Persulfate under occlusive patches. At this concentration and exposure conditions, a mixture of these Persulfates was not sensitizing, and application of Ammonium, Potassium, and Sodium Persulfate did not result in an urticarial reaction. In normal use (i.e., not occluded and rinsed off), it was expected that a concentration greater than 17.5% would also be safe. Given the clinical reports of urticarial reactions, however, manufacturers and formulators should be aware of the potential for urticarial reactions at concentrations of Persulfates greater than 17.5%. Based on the available data, the Cosmetic Ingredient Review (CIR) Expert Panel concluded that Ammonium, Potassium, and Sodium Persulfate are safe as used as oxidizing agents in hair colorants and lighteners designed for brief discontinuous use followed by thorough rinsing from the hair and skin. PMID- 11766135 TI - Final report on the safety assessment of Sodium Metaphosphate, Sodium Trimetaphosphate, and Sodium Hexametaphosphate. AB - These inorganic polyphosphate salts all function as chelating agents in cosmetic formulations. In addition, Sodium Metaphosphate functions as an oral care agent, Sodium Trimetaphosphate as a buffering agent, and Sodium Hexametaphosphate as a corrosion inhibitor. Only Sodium Hexametaphosphate is currently reported to be used. Although the typical concentrations historically have been less than 1%, higher concentrations have been used in products such as bath oils, which are diluted during normal use. Sodium Metaphosphate is the general term for any polyphosphate salt with four or more phosphate units. The four-phosphate unit version is cyclic, others are straight chains. The hexametaphosphate is the specific six-chain length form. The trimetaphosphate structure is cyclic. Rats fed 10% Sodium Trimetaphosphate for a month exhibited transient tubular necrosis; rats given 10% Sodium Metaphosphate had retarded growth and those fed 10% Sodium Hexametaphosphate had pale and swollen kidneys. In chronic studies using animals, growth inhibition, increased kidney weights (with calcium deposition and desquamation), bone decalcification, parathyroid hypertrophy and hyperplasia, inorganic phosphaturia, hepatic focal necrosis, and muscle fiber size alterations. Sodium Hexametaphosphate was a severe skin irritant in rabbits, whereas a 0.2% solution was only mildly irritating. A similar pattern was seen with ocular toxicity. These ingredients were not genotoxic in bacterial systems nor were they carcinogenic in rats. No reproductive or developmental toxicity was seen in studies using rats exposed to Sodium Hexametaphosphate or Sodium Trimetaphosphate. In clinical testing, irritation is seen as a function of concentration; concentrations as high as 1% produced no irritation in contact allergy patients. Because of the corrosive nature of Sodium Hexametaphosphate, it was concluded that these ingredients could be used safely if each formulation was prepared to avoid skin irritation; for example, low concentration in a leave-on product or dilution of a higher concentration as part of product usage. PMID- 11766136 TI - Final report on the safety assessment of Stearamide DIBA-Stearate. AB - Stearamide DIBA-Stearate is a substituted dihydroxyisobutylamine (DIBA) that functions in cosmetic formulations as an opacifying agent, a surfactant-foam booster, and a viscosity increasing agent. Stearamide DIBA-Stearate was reportedly used in four cosmetic formulations, at concentrations of 1% to 3%. Few data on this ingredient were available. Data on related ingredients, including Dibutyl Adipate, Diisopropyl Adipate, Stearamide DEA, and Stearamide MEA, were considered in the assessment of safety. A formulation containing 1.3% Stearamide DIBA-Stearate (further diluted to 4% of the formulation) was mildly irritating but nonsensitizing in an repeated-insult patch test (RIPT). The same dilution was noncomedogenic. At a concentration of 20%, Dibutyl Adipate had an oral LD50 of 2 g/kg. Subchronic dermal exposure of rabbits (1.0 ml/kg/day) caused a reduction in weight gain that was not observed at a dose of 0.5 ml/kg/day. In studies using rabbits, undiluted Dibutyl Adipate caused mild to moderate skin irritation and minimal ocular irritation. When pregnant rats were treated intraperitoneally with approximately 1.75 ml/kg Dibutyl Adipate during gestation, the incidence of fetal gross abnormalities was increased. No effect was observed at smaller doses. Diisopropyl Adipate had low acute oral and percutaneous toxicity, and was only a very mild ocular irritant. In skin irritation studies using rabbits, 5.0% to 100% Diisopropyl Adipate caused minimal to mild irritation; these results were also seen in clinical testing with only moderate cumulative irritation, and no sensitization or photosensitization. A formulation containing 5.27% Stearamide MEA was not toxic to rats when applied topically daily for 13 weeks. In studies using rabbits, Stearamide DEA (35% to 40%) was not a skin or ocular irritant, and Stearamide MEA (5.27%) was not an ocular irritant. At 17%, Stearamide MEA was not irritating to the skin, but caused minimal to moderate irritation to the eyes of rabbits. Stearamide MEA (5.27%) did not cause sensitization during a clinical study. It was not possible, however, to determine the relevance of these data on related ingredients. Therefore, it was concluded that the available data are insufficient. Additional data needs are (1) method of manufacture; (2) chemical characterization, including impurities; (3) dermal absorption; if significantly absorbed, then a 28-day dermal toxicity study and a reproductive and developmental toxicity study may be needed; (4) two genotoxicity assays, at least one in a mammalian system; if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program (NTP) methods may be needed; (5) ultraviolet (UV) absorption data; if significant absorption occurs in the UVA or UVB range, photosensitization data are needed. Absent these data, it was concluded that the available data are insufficient to support the safety of Stearamide DIBA-Stearate as used in cosmetic products. PMID- 11766137 TI - Final report on the safety assessment of Cetethyl Morpholinium Ethosulfate. AB - Cetethyl Morpholinium Ethosulfate is a quaternary salt used as an antistatic agent and as a surfactant in several hair care products. The concentration at which this ingredient is used is unknown, although data reported in 1984 indicated a maximum concentration of 1%. In an inhalation toxicity study, the approximate lethal concentration of Cetethyl Morpholinium Ethosulfate was 0.403 mg/mm3. This ingredient was shown to be a severe ocular irritant in an animal study. No other safety test data on this ingredient were available. These data were clearly insufficient to support the safety of Cetethyl Morpholinium Ethosulfate in cosmetics. Data available on Morpholine were summarized, but these data themselves were insufficient to support safety. The data needed in order to complete the safety assessment of Cetethyl Morpholinium Ethosulfate include: methods of manufacture and impurities, especially nitrosamines; current concentration of use; skin penetration; if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; two genotoxicity studies, at least one in a mammalian system, if positive, then a 2 year dermal carcinogenisis study using National Toxicology Program (NTP) methods may be needed; ultraviolet (UV) absorption data, if significantly absorbed, then photosensitization data are needed; dermal irritation and sensitization; and ocular toxicity, if available. PMID- 11766138 TI - Influences of presentation mode and time pressure on the utilisation of advance information in response preparation. AB - An important approach to the investigation of movement selection and preparation is the precuing paradigm where preliminary information about a multidimensional response leads to reaction time benefits which are positively related to the amount of precue information. This so-called precuing effect is commonly attributed to data-limited preparatory motoric processes performed in advance of the response signal. By means of recording the lateralised readiness potential (LRP), the present experiments investigated whether the precuing effect could be explained also by variables that affect strategic utilisation of stimulus conveyed information. Experiment 1 presented fully and partially informative precues either in mixed or blocked mode. Experiment 2 exerted various degrees of time pressure to the different precue conditions. In both experiments, the precuing effect on reaction times and the LRP was fully preserved, refuting the notion that the sensitivity of the LRP to the amount of preliminary information merely reflects differential precue utilisation. As a major finding, time pressure increased the LRP amplitude during response preparation which is consistent with the view that response strategies generally influence movement preparation on a motoric level. PMID- 11766139 TI - The Eriksen flanker effect revisited. AB - Four studies are reported on the potential role of perceptual interference in a standard Eriksen flanker task. In the first study, incongruent flanker letters showed the usual effect on choice reaction time (CRT) to the target letter but had no effect on the visual fixation time (VFT) needed to distinguish target and flankers. In the second experiment, the effect of incongruent flankers was studied in the context of a same-different response in regard to the target letter and a subsequently presented single letter. The effect of incongruent flankers vanished at an interstimulus interval of 200 ms. In Experiment 3, the same-different task was used in the paradigm of the functional visual field with a target-flankers combination as stimulus on the left (SL) and a single letter as stimulus on the right side (SR) of the visual field. Flankers did neither affect VFT nor the same-different CRT suggesting that target selection may proceed during the saccade from SL to SR. In Experiment 4 effects were studied of flanker to-target and target-to-single-letter similarity. Flanker-to-target similarity did neither affect VFT nor same-different CRT but target-to-single-letter similarity prolonged same-different CRT. Together, the results suggest parallel perceptual processing of target and flankers, followed by competition of responses to the target and to the incongruent flankers. In line with earlier research, processes of response selection and response competition appear not to be tied to VFT but to proceed in parallel with the saccade from SL to SR. PMID- 11766140 TI - Attending to objects: costs or benefits? AB - The single-object advantage is said to occur when performance is faster and/or more accurate when the two targets to be compared appear on one object than when they appear on two different objects. The single-object advantage has been interpreted to suggest that attention can select objects rather than unparsed regions of visual space. In five experiments we explored whether directing attention to one object rather than two objects produces a benefit or a minor cost. Participants were required to compare two target features that belonged to one object, to two objects, or did not belong to any object. In addition, we varied the relevance to the task of object-related global information, such as symmetry of the object and perceptual cluttering of the background. Results showed that attending to one object in comparison to attending to no object produced a benefit only when object-related global information was relevant to the task. In contrast, when object-related global information was irrelevant to the task, attending to one object produced a cost. Thus, it can be concluded that attending to an object does not produce an absolute benefit, but rather produces a smaller cost than attending to two objects. PMID- 11766141 TI - Remembering changes: repetition effects in face recollection. AB - Two experiments examined effects of repetition and change on states of awareness in face recognition. Participants studied repeatedly presented photographs of faces, with the second presentation following either immediately after the first presentation (massed repetition) or following six intervening items (spaced repetition). To manipulate perceptual change, each repeated face was either identical or a mirror image of the first presentation. Subsequently, when recognising a face, participants indicated whether they consciously recollected its prior occurrence ("remembering") or recognised it on the basis of familiarity ("knowing"). Changes in appearance between repeated faces enhanced remember, but not know, responses, and these effects were accentuated for spaced, rather than massed, repetition. These findings suggest that distinctiveness of encoding supports the phenomenological experience of conscious remembering. PMID- 11766142 TI - Nongenetic screening of ovarian malignancies. AB - Ovarian cancer is the leading pelvic reproductive organ cancer health hazard for American women. Seventy percent of women are not diagnosed until the disease is in an advanced stage because of a lack of early warning signals and effective early detection techniques. Understanding the risk factors for sporadic ovarian cancer and the recently recognized inherited susceptibility for ovarian cancer associated with BRCA1 and BRCA2 gene mutations may allow physicians to identify women who might benefit from prophylactic oophorectomy. Current early detection techniques, including serum CA-125 levels and endovaginal ultrasound studies, are of limited value. Strategies to reduce the risk of ovarian cancer in women with increased risk include the use of oral contraceptives and tubal ligations in addition to prophylactic oophorectomy. PMID- 11766143 TI - Human papillomaviruses: into the new millennium. AB - Human papillomaviruses (HPV) are newsworthy in this new millennium. Numerous articles have appeared in the lay press ranging in style and quality from informative essays to sensationalized exposes. Women, sensitized by confusing information, are asking obstetricians hard questions about HPV transmission and prevention, partner notification, the need for HPV testing, and methods of treatment. These questions are difficult because none of the answers are clear cut. This article provides the practicing gynecologist and obstetrician a concise and accurate summary of clinically important issues surrounding HPV. Current knowledge about HPV virology, epidemiology, testing, and the prospects for vaccination and other prevention measures is summarized. PMID- 11766144 TI - Diagnosis and management of cervical intraepithelial neoplasia. AB - Ovarian cancer is the leading cause of death from malignancies arising in the female genital tract. More women die from ovarian cancer than cervical and endometrial cancer combined. All clinicians should understand the concepts of ovarian cancer biology and management. Approximately 90% of all ovarian cancers are epithelial in origin, and such cancers are the focus points of this article. PMID- 11766145 TI - Diagnosis and management of vulvar and vaginal intraepithelial neoplasia. AB - Vulvar intraepithelial neoplasia and VAIN present unique challenges to the practicing gynecologist. VIN may produce distressing symptoms and undergo malignant conversion. A high index of suspicion and liberal use of biopsy are required to make the diagnosis. The approach to therapy for VIN has been reviewed. Treatment should be tailored to each individual patient and may include a period of expectant observation. Variations and combinations are used whenever necessary to preserve normal function and anatomy. Frequent surveillance is a must because recurrence rates are high, especially with multifocal disease in young women. Although VAIN accounts for less than 0.5% of lower genital tract neoplasia, the frequency of its detection is increasing, especially in younger patients. These lesions are most commonly found in the upper third of the vagina and are often multifocal in nature. The close proximity of the upper vagina to the rectum, bladder, and ureters makes treatment difficult. The occult invasion rate may be as high as 28%, and a wide variety of therapies are available. As is true for VIN, recurrence is not uncommon. PMID- 11766146 TI - Current management of perianal intraepithelial neoplasia. AB - The surgical management of intraepithelial perianal neoplasms is straightforward. The goal is complete locoregional control of the disease. Success is determined at the time of operation by frozen section analysis and reexcision if necessary. Procedures that will interfere with sphincter function should be delayed in favor of alternative treatment with radiotherapy or chemoradiotherapy. Close long-term follow-up is necessary to ensure the best possible outcome should a lesion recur. PMID- 11766147 TI - Prevention and treatment of breast cancer. AB - In the new millennium, practitioners who provide primary care for women of all ages must be well educated in the diagnosis and treatment modalities for breast carcinoma. This disease strikes one of eight women. That statistic alone should encourage diligent and persistent efforts to detect this disease early enough to prevent the large number of deaths annually Early detection will reduce the morbidity associated with breast cancer. Strong efforts are ongoing in the fields of genetics and breast cancer research to achieve earlier detection of breast cancer and a reduction in morbidity regardless of the stage of the breast carcinoma. As results of ongoing studies materialize and new studies are funded, it is hoped that more answers will emerge to combat the devastating effects of breast cancer. PMID- 11766148 TI - Cervical carcinoma: contemporary management. AB - Cervical carcinoma is prevented easily with proper screening. Unfortunately, many women in industrialized countries continue to have poor access to adequate medical care. In many third-world countries, cervical cancer is one of the top malignancies diagnosed. Screening should be provided for all women to prevent or diagnose cervical cancer at an early, treatable stage. PMID- 11766149 TI - Endometrial adenocarcinoma: a primer for the generalist. AB - Endometrial cancer is the most common gynecologic malignancy in the United States. The mean and median age of women with endometrial adenocarcinoma is 61 years. Most endometrial cancers are type I estrogen-dependent endometrioid adenocarcinomas. Most women with endometrial adenocarcinoma have stage I disease. Patients with stage I disease endometrial adenocarcinoma can be treated with a simple hysterectomy, bilateral salpingo-oophorectomy, peritoneal lavage, and periaortic node dissection in selected cases. The probability of survival according to international statistics is as follows: stage IA, 91%; stage IB, 88%; stage IC, 81%; stage IIA, 77%; stage IIB, 67%; stage IIA, 60%; stage IIIB, 41%; stage IIC, 32%; stage IVA, 20%; stage IVB, 5%. PMID- 11766150 TI - Contemporary management of ovarian cancer. AB - Major advances in treatment for epithelial ovarian cancer have occurred over the last decade, giving hope to patients and families. Surgery remains a cornerstone of therapy. In early-stage epithelial ovarian cancer, a meticulous staging procedure should be performed to aid in determining patients who require appropriate adjuvant therapy and patients who can be monitored. The patient with advanced epithelial ovarian cancer significantly benefits from aggressive cytoreductive surgery and chemotherapy, affording the patient higher rates of complete response and partial response. In the new millenium, new therapeutic modalities should enhance the current response rates. PMID- 11766151 TI - Role of the ultrasonic surgical aspirator in gynecology. AB - As is true in neurosurgery and general surgery, the ultrasonic surgical aspirator is a powerful tool for the general gynecologist and gynecologic oncologist in assisting in the treatment and management of benign and malignant diseases. The physical properties of ultrasonic sound waves along with the composition of the tissues in question allow for safe, selective, and precise tissue resection. Although the ultrasonic surgical aspirator has had favorable results to date and future applications seem promising, the ultimate role of this device needs to be established with clinical trials. PMID- 11766152 TI - Carcinoma of the vulva. AB - Vulvar cancer will probably become a more common disease as the population ages. It is primarily a disease of the elderly. Fortunately, most vulvar cancers remain localized for extended periods of time and can be treated adequately with radical surgery. PMID- 11766153 TI - Gestational trophoblastic disease. AB - Gestational trophoblastic disease consists of a broad spectrum of conditions ranging from an uncomplicated partial hydatidiform molar pregnancy to stage IV choriocarcinoma with cerebral metastases. Fortunately, with the advent of combination chemotherapy, the patient with advanced-stage disease has a significant chance of achieving complete remission. In addition, several studies have demonstrated that patients with a history of gestational trophoblastic neoplasia do not experience an increased risk of complications with future pregnancies. Patients who have undergone chemotherapy do not seem to experience an increase in the risk for congenital anomalies in their offspring. Patients with a history of hydatidiform molar pregnancy should be advised that they are at increased risk of future molar pregnancies, with a risk of 1% in subsequent gestations after one molar pregnancy and a risk as high as 23% after two molar gestations. Although patients should be reassured regarding their reproductive future, they should be advised to seek prompt medical attention once gestation is suspected so that an early work-up can be initiated if pregnancy is confirmed. PMID- 11766154 TI - The management of pain in the oncology patient. AB - The treatment of cancer pain is improving, but pain remains a significant problem. Although better analgesics with greater efficacy and fewer side effects are needed, the most significant problem regarding the appropriate management of cancer pain remains a lack of knowledge among physicians treating cancer patients. Cancer management should be undertaken within a palliative care model, in which autonomy and respect for individuals and their families guides all aspects of care. PMID- 11766155 TI - Infectious diseases in gynecologic oncology: an overview. AB - The increasing trend of a multimodal therapeutic approach in gynecologic oncology in the last few years has markedly changed the nature, frequency, and clinical presentation of infectious diseases. Despite the improved diagnostic tools, refined surgical technique, and routine use of prophylactic antibiotics, the morbidity and mortality of infectious complications remain significant. The rational use of available treatment resources, the recognition of risk factors, and increased awareness of host-cancer interactions should reduce the incidence of these serious infectious complications. The improved prevention and more efficient treatment of infections in the gynecologic oncology patient will not only improve prognosis but also have a significant economic impact as well. PMID- 11766156 TI - Hypoglossal nerve response to 5-HT3 drugs injected into the XII nucleus and vena cava in the rat. AB - Systemically administered ondansetron, a 5-HT3 receptor antagonist, reduces obstructive sleep-disordered breathing (OSDB) events in the English bulldog. The neural mechanisms through which ondansetron acts are unknown. 5-HT3 receptor immunoreactivity and mRNA have been detected in the vicinity of upper airway dilator motoneurons (UAWDMn's), suggesting that this receptor may contribute to the state-dependent modulation of UADMn's. To characterize 5-HT3 receptor activity within a representative UAWD nucleus, we performed acute microinjections of selective 5-HT3 drugs, 1-(m-Chlorophenyl)-biguanide HCl, an agonist, and ondansetron, an antagonist, into a major population of UADMn's, the hypoglossal nucleus (XII), in anesthetized, paralyzed and mechanically-ventilated rats. The 5 HT3-selective drugs neither altered the baseline XII nerve activity nor the excitatory effect of 5-HT microinjected into the XII. In contrast, systemic administration of ondansetron (3 mg/kg) produced a significant increase in the inspiratory modulation of XII nerve activity (to 195.8%+/-19.3 of control, p<0.001). Together, these data suggest that 5-HT3 receptors within the XII nucleus do not mediate 5-HT effects on XII motoneurons, rather antagonism of 5 HT3 receptors outside the XII nucleus can increase respiratory drive to XII motoneurons. These results highlight the importance of understanding serotonergic effects on respiratory drive outside the UAWD motor nuclei as we search for 5-HT drug therapies for OSDB. PMID- 11766157 TI - Relationship of slow and rapid EEG components of CAP to ASDA arousals in normal sleep. AB - STUDY OBJECTIVES: Besides arousals (according to the ASDA definition), sleep contains also K-complexes and delta bursts which, in spite of their sleep-like features, are endowed with activating effects on autonomic functions. The link between phasic delta activities and enhancement of vegetative functions indicates the possibility of physiological activation without sleep disruption (i.e., arousal without awakening). A functional connection seems to include slow (K complexes and delta bursts) and rapid (arousals) EEG events within the comprehensive term of activating complexes. CAP (cyclic alternating pattern) is the spontaneous EEG rhythm that ties both slow and rapid activating complexes together during NREM sleep. The present study aims at exploring the relationship between arousals and CAP components in a selected sample of healthy sleepers. DESIGN: Polysomnographic analysis according to the scoring rules for sleep stages and arousals. CAP analysis included also tabulation of subtypes A1 (slow EEG activating complexes), A2 and A3 (activating complexes with fast EEG components). SETTING: 40 sleep-lab accomplished recordings. PARTICIPANTS: Healthy subjects belonging to a wide age range (38 +/- 20 yrs.). INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: Of all the arousals occurring in NREM sleep, 87% were inserted within CAP. Subtypes A2 and A3 of CAP corresponded strikingly with arousals (r=0.843; p<0.0001), while no statistical relationship emerged when arousals were matched with subtypes A1 of CAP. Subtypes A1 instead correlated positively with the percentages of deep sleep (r=0.366; p<0.02). CONCLUSIONS: The CAP subtype classification encompasses both the process of sleep maintenance (subtypes A1) and sleep fragmentation (subtypes A2 and A3), and provides a periodicity dimension to the activating events of NREM sleep. PMID- 11766158 TI - Estrogen replacement therapy moderates the sleep disruption associated with nocturnal blood sampling. AB - STUDY OBJECTIVES: To determine whether chronic oral estrogen replacement therapy (ERT) (1) improves the sleep of older, non-symptomatic postmenopausal women; and (2) reduces the sleep disruption associated with a stressor (frequent remote nocturnal blood-sampling through an intravenous catheter). DESIGN: Descriptive, cross-sectional, secondary analysis of a larger study. SETTING: The General Clinical Research Center at the University of Washington Medical Center. PARTICIPANTS: Women aged 57-80 (mean age = 70) at least 5 years past menopause were recruited from the community. Hot flashes and significant sleep difficulties were exclusion criteria. The ERT group (n=37) consisted of women on chronic oral ERT for > or = 2 years. The NERT group (n=56) consisted of women not using estrogen (NERT) for > or = 2 years. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Following an adaptation night, polysomnographic measures were collected for 2 consecutive nights. A blood sample was collected every 20 minutes for the last 24 hours (including Night 2), through an intravenous catheter. The only group difference in sleep on the baseline (non-catheter) night was that NERT women had a shorter sleep latency. Sleep on the catheter night was characterized by increased wakefulness, longer sleep latency, and decreased REM sleep for both groups relative to the baseline. However, the impact of nocturnal blood sampling was much greater for NERT than for ERT women: they experienced significantly greater percent changes in more sleep-wake variables, particularly slow-wave sleep (SWS). CONCLUSIONS: In this cross-sectional study, the use of chronic oral ERT was associated with little effect on the sleep of older postmenopausal women not experiencing hot flashes, except in the presence of a challenge to sleep. ERT ameliorated the disruptive effect of nocturnal blood sampling on both objectively assessed and subjectively assessed sleep. PMID- 11766160 TI - Types of coping strategies are associated with increased depressive symptoms in patients with obstructive sleep apnea. AB - STUDY OBJECTIVES: Some, but not all, researchers report that obstructive sleep apnea (OSA) patients experience increased depressive symptoms. Many psychological symptoms of OSA are explained in part by other OSA comorbidities (age, hypertension, body mass). People who use more passive and less active coping report more depressive symptoms. We examined relationships between coping and depressive symptoms in OSA. SETTING: N/A. DESIGN/PARTICIPANTS: 64 OSA (respiratory disturbance index (RDI) > or = 15) patients were studied with polysomnography and completed Ways of Coping (WC), Profile of Mood States (POMS), Center for Epidemiological Studies-Depression (CESD) scales. WC was consolidated into Approach (active) and Avoidance (passive) factors. Data were analyzed using SPSS 9.0 regression with CESD as the dependent variable and WC Approach and Avoidance as the independent variables. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: WC Approach factor (B=-1.105, beta=-.317, p=.009) was negatively correlated and WC Avoidance factor (B=1.353, beta=.376, p=.007) was positively correlated with CESD scores. These factors explained an additional 8% of CESD variance (p<.001) beyond that explained by the covariates: demographic variables, RDI, and fatigue (as measured by the POMS). CONCLUSIONS: More passive and less active coping was associated with more depressive symptoms in OSA patients. The extent of depression experienced by OSA patients may not be due solely to effects of OSA itself. Choice of coping strategies may help determine who will experience more depressive symptoms. PMID- 11766159 TI - Acute cardiovascular responses to arousal from non-REM sleep during normoxia and hypoxia. AB - STUDY OBJECTIVES: There is uncertainty concerning the relative contribution of arousal, chemoreceptor stimulation, and their potentially interactive effects, to the acute cardiovascular changes observed during sleep in patients with sleep disordered breathing. The purpose of this study was to compare cardiovascular responses (heart rate, skin blood flow, and pulse transit time, a non-invasive measure of arterial wall stiffness) to auditory induced arousal from stage 2 sleep under conditions of normoxia and overnight mild hypoxia. DESIGN: Randomised crossover. SETTING: Sleep Disorders Unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven healthy male subjects. INTERVENTIONS: Subjects slept wearing a facemask and breathed room air (one night; SaO2 approximately 98%) or an hypoxic gas mixture (two nights; SaO2 approximately 92%). Once in stage 2 sleep, subjects were administered one of 10 auditory tones (500 Hz, range 54-90 dB, 5 sec duration) via earphones or a sham tone (recording with no tone). MEASUREMENTS AND RESULTS: Cardiovascular responses were examined beat-by-beat for 20 seconds before and 30 seconds after auditory tones associated with arousals (3-10 second EEG changes) and after sham tones. Sleep efficiency and the percentage of sleep spent in each stage were not different between hypoxia and normoxia nights. Baseline heart rate was elevated on hypoxia nights compared with normoxia nights (59.5+/-1.7 vs. 54.4+/-1.6 b x min(-1), p=0.007). Heart rate, pulse transit time, and skin blood flow showed significant changes after arousal consistent with rapid parasympathetic withdrawal and sympathetic nervous system activation. No changes were observed after sham tones. There were no differences in time course or magnitude of cardiovascular responses between hypoxia and normoxia nights. CONCLUSIONS: We conclude that while mild hypoxia stimulates autonomic activity it does not augment the cardiovascular response to arousal from stage 2 sleep in normal subjects. PMID- 11766161 TI - Self-reported nap behavior and polysomnography at home in midlife women with and without insomnia. AB - STUDY OBJECTIVES: To describe self-reported nap behavior and relationships among nap history, nap behavior during the study, indicators of subjective and objective insomnia, and self-reported daytime sleepiness from data previously obtained in a week-long field study of sleep in midlife women with and without insomnia. DESIGN: Descriptive/comparative secondary analysis. SETTING: Individual homes of the participants. PARTICIPANTS: Midlife women (mean age 46+/-4 years) with self-reported insomnia (n=101) and women with adequate sleep (n=30). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Sleep patterns were assessed by polysomnography (PSG), daily diaries, and a sleep history form. Although all women were requested not to nap, 47% of the women reported nap behavior during the study. Strong relationships were observed between a history of daytime naps and nap behavior (chi2 = 25.63, p < or = .001), and a history of feeling sleepy or struggling to stay awake during the daytime (i.e., sleepiness) and nap behavior (chi2 = 18.05, p < or = .001) during the study. There was also a modest significant (p < or = .05) correlation (r = .25) between tiredness and nap duration during the study. There were no statistical differences in sleep variables between the napping and non-napping groups. In the napping group, there were no differences between women with sleep efficiency < 85% (objective insomnia) and those with sleep efficiency > 85%. CONCLUSIONS: Habitual nap behavior may be indicative of daytime sleepiness in women with insomnia, but it is not necessarily related to subjective or objective measures of insomnia. Women who routinely nap may be unable to refrain from napping during the daytime in long-term research studies. PMID- 11766162 TI - Comparability of sleep disorders diagnoses using DSM-IV and ICSD classifications with adolescents. AB - STUDY OBJECTIVES: The use of diagnostic classifications to define sleep disorders is still unusual in epidemiological studies assessing the prevalence of sleep disorders in an adolescent population. DESIGN: Cross-sectional study. Representative samples of general populations in United Kingdom, Germany and Italy were selected and interviewed by telephone about their sleep habits, sleep and mental disorder diagnoses. Overall, 724 adolescents ages 15-18 years and 1447 young adults ages 19 to 24 years were interviewed. ICSD-90 and DSM-IV diagnoses provided by the Sleep-EVAL expert system were used for the comparisons. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 8% of the adolescents and 12.6% of the young adults had ICSD dyssomnia or sleep disturbances associated with a mental disorder. According to the DSM-IV classification, 5.7% of the adolescents and 8.1% of the young adults had a dyssomnia diagnosis. The comparison between the two classifications show that 73.2% of adolescents and young adults with a DSM-IV dyssomnia diagnosis also had similar ICSD diagnosis. The reverse comparison, ICSD vs. DSM-IV, shows that 39.8% of the subjects with an ICSD diagnosis had a DSM-IV diagnosis. DSM-IV primary insomnia was the most frequent diagnosis. Subjects with such a diagnosis were found in about 10 different ICSD diagnoses, mainly inadequate sleep hygiene, psychophysiological or idiopathic insomnia and insufficient sleep syndrome. CONCLUSIONS: ICSD-90 classification provided higher prevalence of sleep disorder diagnoses than the DSM-IV classification. In adolescents and young adults, DSM-IV primary insomnia is two times more often associated with ICSD inadequate sleep hygiene than with ICSD psychophysiological or idiopathic insomnia. PMID- 11766163 TI - Ethnic differences in self-reported sleep problems in older adults. AB - STUDY OBJECTIVES: To date, conflicting observations have been made regarding ethnic differences in sleep patterns. Plausibly, differing sampling strategies and disparity in the cohorts investigated might help explain discrepant findings. To our knowledge population-based studies investigating ethnic differences in sleep complaints have not addressed within-group ethnic heterogeneity, although within-group health disparities have been documented. DESIGN: Volunteers (n =1118) in this study were community-residing older European Americans and African Americans residing in Brooklyn, New York, which were recruited by a stratified, cluster sampling technique. Trained interviewers of the same race as the respondents gathered data during face-to-face interviews conducted either in the respondent's home or another location of their choice. Data included demographic and health risk factors, physical health, social support, and emotional experience. Relationships of demographic and health risk factors to sleep disturbances were examined in multiple linear regression analyses. Within-group differences in sleep complaints were also explored. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Of the factors showing significant associations with sleep disturbance, European American ethnicity was the most significant predictor (r2 = 0.20). Worse sleep and greater reliance on sleep medicine were observed among European Americans. Caribbean Americans reported less sleep complaints than did U.S.-born African Americans, and immigrant European Americans reported greater complaints than did US-born European Americans. CONCLUSIONS: As expected several health risk factors were predictive of sleep disturbance among urban community-dwelling older adults, but ethnicity was the most significant predictor. The present data suggest both between-group and within-group ethnic differences in sleep complaints. Understanding of demographic and cultural differences between African Americans and European Americans may be critical in interpreting subjective health-related data. PMID- 11766164 TI - Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA). AB - STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited. DESIGN: A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. SETTING: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home. PARTICIPANTS: Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5-8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants. INTERVENTIONS: N/A. MEASUREMENTS & RESULTS: Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory. CONCLUSIONS: The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5-12 years in an unattended setting under a research protocol. PMID- 11766165 TI - The mind in REM sleep: reports of emotional experience. AB - STUDY OBJECTIVES: No consensus has been reached on the characteristics of emotional experience during rapid eye movement sleep (REM). Thus, the relationship between the emotional brain activation and mental activity in REM remains unclear. Our objective is to characterize emotional experience in REM in order to facilitate understanding of brain-mind correlations in this state. DESIGN: We combined instrumental awakenings from REM with the subjects' own ratings of the occurrence and intensity of discrete emotion types for each line in their REM mentation reports. SETTING: The study was performed in the subjects' own homes over three consecutive nights using ambulatory polysomnography. PARTICIPANTS: Nine normal healthy subjects, age 31-60 (mean=43.0). INTERVENTIONS: Awakenings 5-15 minutes into REM periods across the night. MEASUREMENTS AND RESULTS: Emotions were found in 74% of 88 mentation reports, with a balanced proportion of positive and negative emotions. Among the reports scored for emotions, 14% contained one emotion and 86% contained two or more different emotion types. Joy/elation was the most frequent emotion, found in 36% of the reports, followed by surprise (24%), anger (17%), anxiety/fear (11%), and sadness (10%). Anxiety/fear was significantly less intense than joy/elation, anger, and surprise. Except for surprise, no specific emotion type changed from the first to the second half of the night. Negative emotions and surprise but not positive emotions varied significantly across subjects. CONCLUSIONS: The analysis of subject reports of emotions following instrumental awakenings demonstrate a balanced and widespread occurrence of both positive and negative emotions in REM sleep dreams. Emotions in REM are likely to be powerfully modulated by the neurobiological processes which differentiate REM from waking. PMID- 11766166 TI - How accurately does wrist actigraphy identify the states of sleep and wakefulness? AB - STUDY OBJECTIVES: Because sleep and wakefulness differ from each other by the amount of body movement, it has been claimed that the two states can be accurately distinguished by wrist actigraphy. Our objective was to test this claim in lengthy polysomnographic (psg) and actigraphic (acf) samples that included night and day components. DESIGN: Fourteen healthy young (21-35 years) and old (70-72 years) men and women lived in a laboratory without temporal cues for 7 days. Each subject continuously wore sleep-recording electrodes as well as 2 wrist-movement recorders. Act measurements were converted to predictions of sleep and wakefulness by simple-threshold and multiple-regression methods. Psg served as the gold standard for calculation of predictive values (PV, the probability that an act prediction is correct by psg criteria). SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The 7-day act recordings showed clear circadian cycles of high and low activity that respectively corresponded to subjective days, when subjects were wakeful, and subjective nights when they slept. Lower act levels corresponded to deeper states of psg sleep. Logistic regression on a 20-minute moving average of act gave the highest overall PV's. Nevertheless, the mean PV for sleep (PVS) was only 62.2% in complete, day + night samples. PVS was 86.6% in night samples. Act successfully predicted wakefulness during subjective nights (PVW = 89.6) and accurately measured circadian period length and the extent of sleep-wake consolidation, but it overestimated sleep rate and sleep efficiency. Act systematically decreased before sleep onset and increased before awakening, but reliable transitions among joint psg/act states (the Markov-1 property) were not demonstrated. CONCLUSIONS: Low PV's and overestimation of sleep currently disqualify actigraphy as an accurate sleep-wake indicator. Actigraphy may, however, by useful for measuring circadian period and sleep-wake consolidation and has face validity as a measure of rest/activity. PMID- 11766167 TI - Associations of polycyclic organic matter in outdoor air with decreased birth weight: a pilot cross-sectional analysis. AB - The association between births that are small for gestational age and outdoor airborne polycyclic organic matter (POM) was examined in New Jersey, a highly urban state. This pilot study utilizes a cross-sectional investigation combining maternal and pregnancy outcome information from birth certificates with air toxics data from the U.S. Environmental Protection Agency Cumulative Exposure Project and census data at the census tract level. The exposure categories were based on tertiles of modeled average POM concentrations for each census tract in New Jersey. High POM exposure was positively associated with delivery of "small for gestational age" (SGA) births. After adjustment for potential individual level confounding factors, the odds ratios for term, preterm, and all SGA were 1.22 (1.16-1.27), 1.26 (1.07-1.49), and 1.22 (1.17-1.27), respectively, for the highest exposure tertile in the urban population of the state (89% of the state's birth population). For group-level variables, the corresponding ORs were 1.12 (1.07-1.18), 1.23 (1.02-1.47), and 1.13 (1.07-1.18). The results of this study suggest that residential exposure to airborne polycyclic organic matter (POM) is associated with increased prevalence of "small for gestational age" births among urban population. Cross-sectional investigations combining air dispersion models with routinely collected population-based health and census data could be a useful approach for identifying the hazardous air pollutants of greatest public health concern. PMID- 11766168 TI - Metabolic polymorphisms and urinary biomarkers in subjects with low benzene exposure. AB - The effect of some common metabolic polymorphisms on the rate of trans,trans muconic acid (TMA) and S-phenylmercapturic acid (SPMA) excretion was investigated in 169 policemen exposed to low benzene levels (<10 microg/m3) during the work shift. End-shift urinary concentrations of TMA and SPMA, normalized to unmetabolized blood benzene concentration, were used as indicators of individual metabolic capacity. CYP2E1, NQO1, GSTM1, and CSTT1 polymorphisms were analyzed in all subjects by polymerase chain reaction (PCR) restriction fragment length (RFL). The results obtained show significantly elevated levels of TMA and SPMA in urine of smokers compared to nonsmokers, whereas no correlation with environmental benzene was observed. TMA/blood benzene ratio was partially modulated by glutathione S-transferase (GST) genotypes, with significantly higher values in null individuals (GSTM1 and GSTT1 combined). However, a greater fraction of total variance of TMA/blood benzene in the study population was explained by other independent variables, that is, season of sampling, smoking habits, and gender. Variance in SPMA/blood benzene ratio was only associated with smoking and occupation, whereas no significant role was observed for the metabolic polymorphisms considered. These results suggest that in a population exposed to very low benzene concentrations, urinary TMA and SPMA levels are affected to a limited extent by metabolic polymorphisms, whereas other factors, such as gender, lifestyle, or other confounders, may account for a larger fraction of the interindividual variability of these biomarkers. PMID- 11766169 TI - Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. AB - The effects of deoxynivalenol (DON or vomitoxin) and four closely related 8 ketotrichothecenes on proinflammatory cytokine and chemokine production were evaluated in a clonal human macrophage model. U-937 cells, which represent a human monocytelike histocytic lymphoma, were differentiated into macrophages by preincubation with phorbol 12-myristate 13-acetate (PMA). Differentiated macrophages were incubated with DON in the absence or presence of lipopolysaccharide (LPS), and supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA) for the proinflammatory cytokines interleukin-6 (IL 6) and tumor necrosis factor-alpha (TNF-alpha), and for the chemokine interleukin 8 (IL-8). In the absence of LPS, DON at 500 or 1,000 ng/ml upregulated TNF-alpha production as early as 3 h and up to 6 h, whereas 100 to 1,000 ng/ml of DON significantly increased production of IL-6 from 3 to 24 h and IL-8 from 6 to 48 h. In cells costimulated with 0.2 microg/ml LPS, DON at 500 or 1000 ng/ml markedly superinduced TNF-alpha and IL-8 production. Although 100 ng/ml of DON also potentiated LPS-induced IL-6 production, 500 or 1,000 ng/ ml of the toxin suppressed the LPS-induced IL-6 response. Four other 8-ketotrichothecenes, fusarenon X, nivalenol, 3-acetyl DON, and 15-acetyl DON, were also capable of upregulating or suppressing TNF-alpha, IL-6, and IL-8 production at concentrations similar to that of DON. In total, the results suggest that DON and other 8-ketotrichothecenes have the potential to both directly induce and superinduce proinflammatory cytokine and chemokine expression in human macrophages, even at toxin concentrations that are cytotoxic. PMID- 11766170 TI - Increased risk of preterm delivery in areas with air pollution from a petroleum refinery plant in Taiwan. AB - The petrochemical and petroleum industries are among the main sources of industrial air pollution in Taiwan. Data in this study concern outdoor air pollution and the health of individuals living in communities in close proximity to a petroleum refinery plant. The prevalence of delivery of preterm birth infants was significantly higher in mothers living in a petroleum refinery area compared to controls in Taiwan. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.41 (95% CI = 1.08-1.82) for delivery of preterm infants in the polluted region. Data support the view that air pollution can affect the outcome of pregnancy. PMID- 11766172 TI - Metabolism of territrem a in liver microsomes from wistar rats: 2. Sex differences and regulation with gonadal hormones and phenobarbital. AB - The aim of the present study was to assess the effects of sex difference on metabolism of territrem A (TRA) by liver microsomes from 7-wk-old Wistar rats. Metabolism of TRA to 2-dihydro-4beta-demethylterritrem A (MA2) through 4beta hydroxymethyl-4beta-demethylterritrem A (MA1) and 4beta-oxo-4beta demethylterritrem A (MAX) was observed in intact male rats. However, in intact female rats only MA1 was formed, although the amount of MA, formed in females was much less than in males. Phenobarbital pretreatment enhanced this step and was not affected by gonadectomy. In the gonadectomized rats of both sexes, MA2 was formed from TRA when the animals were further treated by testosterone and was significantly enhanced by treatment with phenobarbital. However, estradiol treatment or estradiol in combination with phenobarbital treatment did not affect MA2 formation from TRA in gonadectomized rats. PMID- 11766171 TI - Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats. AB - Tremorogenic beta-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to beta-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major beta carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/kg), the concentration-time profiles of harmane or harmine fit well with a two-compartment model. While both compounds had comparable elimination t 1/2beta (24 and 26 min for harmane and harmine, respectively), the systemic clearance (CLs) for harmine (103.2 ml/kg/ml) was two times greater than that for harmane (52.2 ml/kg/ml). Accordingly, the area under the blood concentration-time curve (AUC) in harmane-treated rats was 2.7-fold greater than that in harmine-treated rats. Harmine appeared to distribute to tissues better than harmane, with a larger volume of distribution (V,d) (3.9 and 1.6 L/kg for harmine and harmane, respectively). After an oral dose (20 mg/kg), the absolute bioavailability (F) was 19% for harmane and 3% for harmine. Harmane was absorbed more slowly (lower Ka), yet more completely (higher Cmax' AUC, and F) than harmine. An oral administration of harmane resulted in blood harmine whose formation accounted for 13% of the ingested harmane, indicating a biotransformation of harmane to harmine. These results suggest that harmane is absorbed into the systemic circulation more completely than harmine. Upon entering the body, harmane can be metabolized to form harmine; the latter may better distribute to the tissue compartment. PMID- 11766173 TI - An historical tour of vascular injury management: from its inception to the new millennium. AB - Advances have been made in times of war. Lessons learned from these experiences should be studied in order to avoid the costly mistakes made previously. Fortunately, major conflicts have not been common recently. Therefore, military surgeons depend on the stable environment of civilian trauma and research to lead the way. Documentation and careful record keeping such as the Vietnam Vascular Registry are vital in assisting surgeons with lessons to be learned. PMID- 11766174 TI - Current controversies in shock and resuscitation. AB - Many controversies and uncertainties surround resuscitation of hemorrhagic shock caused by vascular trauma. Whereas the basic pathophysiology is better understood, much remains to be learned about the many immunologic cascades that lead to problems beyond those of initial fluid resuscitation or operative hemostasis. Fluid therapy is on the verge of significant advances with substitute oxygen carriers, yet surgeons are still beset with questions of how much and what type of initial fluid to provide. Finally, the parameters chosen to guide therapy and the methods used to monitor patients present other interesting issues. PMID- 11766175 TI - Newer diagnostic modalities for vascular injuries: the way we were, the way we are. AB - The article discusses the role of modalities in diagnosing vascular injuries starting with angiography and tracing the evolution of the use of color flow Doppler, CT, and CT angiography. It also addresses the controversy of minimal vascular injury and outlines vascular injuries that may be safely observed and followed-up. Finally, the evolution from angiography to the use of helical CT for the diagnosis of thoracic aortic injuries is reviewed in detail. PMID- 11766176 TI - Interventional techniques in vascular trauma. AB - This article addresses in detail the newer role for interventional angiography, including diagnosis and newer angioembolization techniques used to control bleeding and to deal with complications of vascular injuries. PMID- 11766177 TI - Anatomic exposures for vascular injuries. AB - The exposure of vascular injuries is contingent on knowledge of anatomy and the limitations and boundaries for proximal and distal control of each artery. In this article, these are conveniently organized into arteries of the neck, of the chest, of the abdomen, and of the extremities. In addition, the interface between the neck and chest, and the chest and the abdomen provide particular challenges because of the need to expose two body regions frequently. The anatomy, the points of proximal and distal control, the details of exposure, and the key maneuvers required to expose particular arteries are reviewed. PMID- 11766178 TI - Cervical vascular injuries: carotid and jugular venous injuries. AB - This article explores the management of carotid arterial injuries, detailing the historical evolution for the management of these injuries and delineating techniques for cerebral perfusion and preservation with shunts. It discusses the role of autogenous versus synthetic grafts in the management of these injuries and the issue of vascular complications and potential pitfalls. Jugular venous injuries are addressed also, with emphasis on the controversies of primary repair versus ligation. PMID- 11766179 TI - Vertebral artery injuries. AB - Vertebral artery injuries are identified more frequently now than in the past for both penetrating and blunt trauma. This is as a result of increased suspicion and awareness, liberal use of color flow Doppler, CT angiography, and traditional four-vessel angiography. The vast majority of patients who are not exsanguinating at the time of presentation can be managed nonoperatively or by angiographic embolization. Operative management should be reserved only for patients with severe active bleeding or when interventional radiology fails. The surgical exposure is complex and demands excellent knowledge of the local anatomy. PMID- 11766180 TI - Subclavian and axillary vascular injuries. AB - Injuries to the subclavian or axillary vessels are associated with a high mortality rate and only patients with short prehospital periods or contained bleeding survive long enough to be treated. The surgical exposure of these vessels can be difficult and excellent knowledge of the local anatomy is critical. This article describes the anatomy, epidemiology, diagnosis, and surgical exposure of these injuries. Newer diagnostic and therapeutic modalities are discussed also. PMID- 11766181 TI - Thoracic aortic and thoracic vascular injuries. AB - Patients with thoracic vascular injuries fall into two groups: those who are exsanguinating and require an empiric operation with a high mortality and those with contained injuries that permit preoperative evaluation. The unstable group requires judgment to determine the appropriate empiric position, exposure, and operation. Unlike abdominal trauma, which is addressed by way of a midline incision, there are multiple thoracic incisions that can be used to access thoracic vascular injuries. Thus, the stable group may benefit from preoperative imaging, which then can suggest a patient position, incision, and operative approach. Avoiding overaggressive resuscitation, obtaining appropriate imaging studies, choosing an operative strategy to achieve proximal and distal control, and using adjuncts based on the injury can make the care of these patients a rewarding but challenging activity. PMID- 11766182 TI - Abdominal vascular injuries: injuries to the aorta. AB - This article discusses injuries to the abdominal aorta at its supra- and infrarenal positions, focusing on the surgical approaches to abdominal aorta injuries and renal vascular pedicles. The controversy regarding the use of bioprosthetic materials and the coLlective experience with these injuries as reported in the literature are reviewed. Primary renal artery repair versus nephrectomy also is examined. PMID- 11766183 TI - Renal vascular injuries. AB - Even today, most renal vascular injuries result in loss of renal function. Kidney salvage is not possible because of late diagnosis and the presence of severe associated injuries. Physical exam and basic laboratory tests are not sensitive; thus, a high index of suspicion is required. Repair should be attempted for all solitary kidneys and for patients sustaining bilateral injuries. All viable kidneys should be revascularized in order to increase the chances of obtaining adequate functional renal tissue. In the event that revascularization is not feasible, nephrectomy can be performed at a later time, if hypertension develops. In some cases, delayed return of function is possible, but in most cases the kidney will atrophy without producing hypertension. Most importantly, maintaining a high index of suspicion, prompt diagnostic evaluation, and judicious treatment can optimize outcome lowering the significant morbidity and mortality of renal vascular injuries. PMID- 11766184 TI - Injuries of the inferior vena cava. AB - Injuries of the IVC, whether caused by blunt or penetrating mechanisms, are usually fatal. Patients who arrive in shock and fail to respond to initial resuscitative measures, those who are still actively bleeding at the time of laparotomy, and those with wounds of the retrohepatic vena cava have a low probability of survival. Death most commonly is caused by intraoperative exsanguination. Knowledge of the anatomy and exposure techniques for the five different segments of the intra-abdominal vena cava is very important to trauma surgeons. Although some wounds of the vena cava, especially those of the retrohepatic vena cava, are best left unexplored, most injuries inferior to this level can be exposed and repaired by lateral suture technique. Preservation of a lumen of at least 25% of normal is probably important in the suprarenal vena cava but is of no provable value inferior to the renal veins. No evidence supports the need to expose and repair vena caval wounds that have spontaneously stopped bleeding. Such wounds, especially in the retrohepatic area, may be managed expectantly provided that there is no strong suspicion of an associated injury to a major artery or hollow viscus. PMID- 11766185 TI - Portal vein injuries. AB - Wounds of the portal vein are caused most commonly by penetrating trauma and carry a very high mortality rate. Most deaths are caused by exsanguination, occurring intraoperatively as surgeons struggle to control the hemorrhage from the portal vein and associated vascular injuries. A thorough knowledge of the anatomy of the area and of the likely patterns of wounding is important. At surgery, surgeons must be prepared to deal with multiple vessel wounding. Although most investigators have advocated lateral repair of the portal vein when it can be accomplished, portal ligation seems to be a safe alternative. Complex repairs are justified only when a contraindication to ligation exists. Postoperative care must recognize the need for extraordinary fluid replacement and the small risk for postoperative bowel infarction after repair or ligation of the portal vein. PMID- 11766186 TI - Preparing for a mass casualty event. PMID- 11766187 TI - Managing people and resources effectively. PMID- 11766188 TI - The power of preparation. PMID- 11766189 TI - Talking to each other in a crisis. PMID- 11766190 TI - Caring for our own. PMID- 11766191 TI - The need for a national bioterrorism response. PMID- 11766192 TI - Nuclear, biological, and chemical decontamination. PMID- 11766193 TI - Responding effectively in the midst of a natural emergency. PMID- 11766194 TI - Developing practical emergency management education programs. PMID- 11766195 TI - Using JCAHO standards as a starting point to prepare for an emergency. PMID- 11766196 TI - What the survey process expects of your organization. PMID- 11766197 TI - Analyzing your vulnerability to hazards. PMID- 11766199 TI - Common pediatric surgical problems. PMID- 11766198 TI - The clinical application of intuition. PMID- 11766200 TI - Evaluation of the child with suspected appendicitis. PMID- 11766201 TI - Evaluation and management of inguinal and umbilical hernias. PMID- 11766203 TI - Pyloric stenosis. PMID- 11766202 TI - Gastrointestinal foreign bodies. PMID- 11766204 TI - Evaluation and initial management of miscellaneous pediatric surgical problems. PMID- 11766205 TI - The AMS revolution--primary care, quality assurance, capabilities and competence. PMID- 11766206 TI - Occupational health and safety issues in military field hospitals. AB - This paper considers the occupational health and safety issues that apply within a military field hospital. It considers NHS occupational health and safety activities and examines how these might be applied within an Army Medical Services unit. Areas that are unique to field hospitals are highlighted in comparison with a static NHS hospital. Some issues for future work are also considered. PMID- 11766207 TI - Occupational health development in the Army. AB - Occupational Health (OH) in the Army is provided as part of an integrated primary healthcare service. When compared to the International Labour Organisation criteria for the provision of OH, it can be seen that the Army provides all of the OH elements expected in a large national organisation. However, there is a need to enhance the clinical element of the service and to provide a focus for implementing OH policy at unit level. The use of qualified OH nurses based at GP group practices and providing a visiting service to units would rectify this balance as this would enable workplace assessments to be carried out on a regular basis, enhance the ability to carry out occupational health assessments and facilitate health surveillance data collection. The result would be the improved delivery of OH services to Army personnel, thus helping to maximise the number of soldiers and officers fit to carry out their military duties. PMID- 11766208 TI - The role of ultrasound in trauma. PMID- 11766210 TI - Rescue of the remnants: the British emergency medical relief operation in Belsen Camp 1945. AB - The British Army liberated the German concentration camp at Belsen on April 15, 1945. The thousands of inmates (estimates range from 60,000 to 78,900 inmates), mostly Jews from eastern Europe, were dying at a rate of 500-600 per day from disease, and many more were being killed by the German guards and co-workers. Diseases prevalent included typhus, tuberculosis, nutritional and infective diarrhoea, severe malnutrition and starvation, and others. Despite huge obstacles including the ongoing war effort, shortages of supplies, and limited numbers of workers, a relief operation was rapidly organized to control the typhus epidemic and salvage as many inmates as possible. The 10,000 emaciated corpses which had been lying all over the camp were collected and buried in mass graves. Inmates were disinfected with D.D.T., scrubbed in a "human laundry," and evacuated from the typhus-ridden Horror Camp (Camp 1) to a hospital organized in the barracks of the Panzer Training School (Camp 2). Feeding of the inmates was carefully regulated, and some basic medical treatment organized. The relief operation was performed by British Army units, detachments of the British Red Cross, British and Belgian medical students, and other volunteers including those from among the less debilitated inmates. Although 13,000 inmates died after the liberation despite the relief operation, thousands of others were rescued. PMID- 11766209 TI - Malaria remains a military medical problem. AB - OBJECTIVE: To bring military medical problems concerning malaria to the attention of the Defence Medical Services. METHOD: Seven military medical problems related to malaria are illustrated by cases referred for secondary assessment over the past five years. Each is discussed in relation to published data. RESULTS: The cases of failure of various kinds of chemoprophylaxis, diagnosis and treatment of malaria may represent just a fraction of the magnitude of the overall problem but in the absence of reliable published military medical statistics concerning malaria cases, the situation is unclear. CONCLUSION: Present experience suggests there are a number of persisting problems affecting the military population in relation to malaria. Only publication of reliable statistics will define their magnitude. Interim remedies are proposed whose cost-effectiveness remains to be established. PMID- 11766211 TI - Physician assistants--a missed opportunity in the British Army? PMID- 11766212 TI - The dangers of sport on an operational deployment. AB - This study, a retrospective review of the orthopaedic outpatient work from a multinational hospital in Bosnia, further confirms the dangers of sport on an operational tour. Sports injuries were shown to be a major cause of morbidity, affecting both the operational effectiveness of the force and also resulting in a number of career-threatening injuries. In particular, football was shown to be the most common cause of injury and the wisdom of allowing this sport during operational tours must be questioned. PMID- 11766213 TI - Assessing exposures in the United Kingdom's Armed Forces--a review of systems that collect data useful for exposure assessment. AB - The ability to assess the exposure of individuals or groups is a critical element in any effective health surveillance system, as it provides the opportunity to identify the causes of ill health, the levels of exposure resulting in ill health and, through controlling exposures, to protect the health of Service personnel. As part of a wider programme to enhance the health surveillance capabilities of the Defence Medical Services, a project was undertaken to assess the collection and retention of data for exposure assessment in the United Kingdom's Armed Forces. The systems investigated include those for health, safety and environment policy, personnel and pay, medical records, environmental and occupational monitoring and historical records. It was found that the use of many systems for exposure assessment would be hampered by inconsistencies in the data collected, poor accessibility and linkage, and variability in the retention of the data. This paper highlights some of the problems that limit the usefulness of the record systems for exposure assessment and summarizes the principal recommendations made for enhancing the systems to better facilitate health surveillance. PMID- 11766214 TI - Retroperitoneal gas gangrene complicating elective inguinal hernia repair. AB - Gas gangrene is a well recognised complication of contaminated military wounds. A case of Clostridial myonecrosis following elective inguinal hernia repair is described. The pathology, clinical features and management of this life threatening condition are reviewed. PMID- 11766215 TI - Trismus due to bilateral mandibular coronoid hyperplasia. AB - Bilateral mandibular coronoid hyperplasia is a rare cause of restricted mouth opening. Diagnosis of the condition prior to general anaesthetic is essential, as oral intubation may be impossible. The reported case illustrates the role of computed tomography in assessment of the disorder and effective treatment by coronoidectomy. PMID- 11766216 TI - Battlefield Advanced Trauma Life Support (BATLS). PMID- 11766217 TI - Pre-hospital anaesthesia. AB - Effective management of the airway may have the greatest impact on mortality and morbidity of all pre-hospital interventions. The administration of a pre-hospital anaesthetic may not only facilitate effective management and protection of the airway but may also be fundamental to maintaining adequate ventilation and reducing times to definitive treatment for casualties who are trapped and those with major chest and head injuries. Pre-hospital anaesthesia is a highly skilled technique that requires considerable training and experience. Inappropriate attempts to anaesthetise critically injured casualties may prove fatal if the operator does not have the requisite knowledge, skills and equipment. For those that do, this article provides an operational framework within which pre-hospital anaesthesia can be developed (Box 5). PMID- 11766218 TI - Self assessment exercises in tropical remote medicine. PMID- 11766219 TI - A career in military psychiatry? PMID- 11766220 TI - Preparing for the FRCA--Fellow of the Royal College of Anaesthetists. Part 1. PMID- 11766221 TI - Write a case report. AB - Case reports are often seen as a relatively easy way of getting published. Despite this, much wasted time and effort on the part of authors, reviewers and editors might be saved if intending authors followed some simple guidelines before committing themselves to paper. The rejection rate for case reports is extremely high. There are two main reasons for this: inappropriate case selection and inadequate attention to detail in case preparation. This article aims to offer a template to the clinician who is considering writing a case report, in order to make the most efficient use (in terms of published results) of the time available. PMID- 11766223 TI - What is forward surgery? PMID- 11766222 TI - Medical support on a trans-atlantic sailing expedition. PMID- 11766224 TI - Shaping the battlespace--an additional role for the DMS? PMID- 11766225 TI - The euthanasia debate. AB - Debates about the moral dilemmas of euthanasia date back to ancient times. Many of the historical arguments used for and against the practice remain valid today. Indeed, any form of discussion on the subject often provokes emotive responses, both from members of the medical profession and the general public. For this reason alone, the issue will continue to be debated at all levels of society. There are, however, other factors that ensure euthanasia will remain a subject of major controversy within medical, legal and governmental bodies. Firstly, the act of euthanasia itself is illegal, yet in its passive form occurs on a daily basis in many of our hospitals (1). Secondly, medical advances have made it possible to artificially prolong the life of an increasing number of patients far beyond what was possible only a few years ago. Furthermore, we must all contend with the reality that financial constraints are an important consideration in modern health care provision. Finally, there is an ethical difficulty in interpreting the concept of a patient's right, or autonomy, versus the rights and duty of a doctor. Before attempting to answer the questions posed by these issues, it is important to have some accurate definitions of both euthanasia and of the concept of morality. According to the House of Lords Select Committee on Medical Ethics, the precise definition of euthanasia is "a deliberate intervention undertaken with the express intention of ending a life, to relieve intractable suffering" (2). The term can be further divided into voluntary and involuntary euthanasia. The former is said to occur if a competent patient makes an informed request for a life terminating event and the latter can be used if a patient does not give informed and specific consent for such treatment. It is the occurrence of involuntary euthanasia which forms one of the main arguments against legalisation. This is discussed in greater detail below. Euthanasia is frequently separated into active and passive forms. A number of authors consider these terms to be misleading and unhelpful. They are, however, used in the literature and in discussion and consequently should be understood. Active euthanasia takes place if deliberate steps are taken to end a patient's life; this would include administration of potassium containing compounds to induce cardiac arrest, a practice that is illegal in this country. Passive euthanasia is the withholding of treatments necessary for the continuance of life. Whether the administration of increasingly necessary, albeit toxic doses of opioid analgesia is regarded as active or passive euthanasia is a matter of moral interpretation, but in order to pacify doctors' consciences, it is usually regarded as a passive measure. Many people, therefore, regard it as an acceptable facet of good professional practice. PMID- 11766226 TI - The first field dressing. PMID- 11766227 TI - [The neonatal receptor Fc gamma(FcRn)--structure and function]. AB - The neonatal Fc receptor (FcRn) is named for the source from which it was first purified, the intestinal epithelium of neonatal rats. The human homologue of FcRn was first found in the placenta, where is presumably involved in transfer of maternal IgG to the fetus. FcRn has since been found in capillary endothelium, intestinal epithelium and other tissues. More recent data has indicated that FcRn has a function beyond the transfer of maternal IgG--the maintenance of constant serum IgG levels. This review summarizes the status of our knowledge on the structure, expression and function of the neonatal Fc gamma receptor. PMID- 11766228 TI - [Role of Wnt signaling and APC protein in the etiology of colorectal cancer]. AB - In this paper we present recent data on molecular function of APC protein and Wnt signaling pathway. Role of a link between APC and Wnt signaling in the etiology of colorectal cancer as well as significance of a mutant APC mice as a model of cancer in man are discussed. PMID- 11766229 TI - [Nitric oxide (NO) in the pathophysiology of asthma and interstitial lung diseases]. AB - NO is an important mediator of immune and inflammatory responses. NO is produced from L-arginine by three isoforms of nitric oxide synthase (NOS), neuronal (nNOS; NOS1), endothelial (eNOS; NOS3) and inducible (iNOS). Exhaled NO has been shown to be increased in asthma and has been put forward as a marker of airways inflammation. Moreover, increased production of NO and peroxynitrite may be responsible for the oxidative damage and fibrosis seen in interstitial lung diseases. The present review focuses on clinical and laboratory studies that are aimed at identifying the role of NO in the physiopathology of these disorders. PMID- 11766230 TI - [Role of lipases in human metabolism]. AB - Lipases play a crucial role in the metabolism of lipids in humans. These enzymes can be classified according to the location: located in the digestive juices (lingual lipase, gastric lipase and pancreatic lipase), located intracellularly (hormone-sensitive lipase and lysosomal acid lipase) and in the endothelial cells (lipoprotein lipase and hepatic lipase). In this review, we discuss the interrelationships of lipases, their structure in humans, how they are affected by hormones and the clinical aspects of their deficiency. PMID- 11766231 TI - [X-inactivation studies in women with structural X chromosome aberrations]. AB - The article presents influence of X inactivation patterns on phenotype of patients with structural X chromosome aberrations. PMID- 11766232 TI - [Cytokines in allergic inflammatory process]. AB - In our review article we intend to show the importance of IL-4, IL-5, IL-13, IL 10, IFN gamma and IL-12 in pathomechanism of allergic inflammatory process, especially in bronchial asthma. We also want to illustrate the relationships between lymphocytes T, monocytes, macrophages, eosinophils and other inflammatory cells which take part in allergic inflammation. PMID- 11766233 TI - [Functional imaging (PET and SPECT) in epilepsy]. AB - Epilepsy is one of the most prevalent neurologic disorders and affects approximately 1% of the population. Most complex seizures arise from the temporal lobes and the condition of 20-30% of these patients is refractory to medication. Many can be rendered seizure free with surgery. Epilepsy surgery requires accurate identification of the site and extent of the epileptogenic area responsible for seizures. EEG is accepted as a gold standard, however only 50% of the patients are safely diagnosed. The need for invasive monitoring with possible hemorrhage or infection has been greatly reduced by the introduction of new technologies such as PET, SPECT and MRI in the clinical practice. MRI demonstrate morphologic changes in approximately 80% of patients with epilepsy. However, structural lesions may not always correlate with clinical, EEG and pathologic localization of epileptogenic foci. Seizures are associated with pronounced changes in regional cerebral blood flow. The real power of SPECT lies in the opportunity of ictal examinations, with a sensitivity ranging from 90 to 97%. Interictal PET studies using 18F-FDG measure regional glucose metabolism, have been investigated for their value as non-invasive focus-localizing techniques. These studies have sensitivity ranging from 80 to 85%. The benzodiazepine binding site that are associated with and modulate the activity of GABA receptors have been imaged by SPECT (using 123I-iomazenil) and PET (using 11C-Flumazenil). Combined measurements of benzodiazepine binding sites and perfusion/metabolism provide a more accurate visualization of epileptogenic site than perfusion or metabolism measurements alone. Functional imaging modalities (PET and SPECT) are highly important in the presurgical evaluation of patients with medically refractory complex partial seizures. PMID- 11766234 TI - [Biological aspects of the effectiveness/ineffectiveness of thrombocyte transfusions]. AB - The clinical effect of platelet transfusions depends on a series of different factors and therefore it is not easy to explain the cause of inefficiency or that of the side-effects. Not only the immunhematological state of the patient, but the medical treatment and the properties of the platelet preparations should be taken into account. Platelet products prepared by standard techniques and stored according to the international recommendations possess different hemostatic effect. The effect of platelet storage conditions, aspects of platelet thermophysiology and current international tendencies regarding preparation and storage of platelet products are discussed. The choice of the proper platelet product has an essential impact on the clinical outcome. PMID- 11766235 TI - [Effect of retinoic acid on the cytogenetic remission in the first chronic phase of chronic myeloid leukemia treated with interferon]. AB - Cytogenetic responses of 11 chronic myeloid leukemic (CML) patients during the first chronic phase, treated with the combination of all-trans retinoic acid (ATRA) + interferon (IFN) were compared to 9 other CML patients of phase one, treated with interferon monotherapy. Metaphase and interphase cytogenetics and a semiquantitative polymerase chain reaction (PCR) were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + interferon treated group were withdrawn, one of them because of interferon intolerance, and the other because of compliance failure. Among the 9 ATRA + interferon treated patients 6 major cytogenetic responses could be detected and 3 of them were complete. Of the 9 patients treated with IFN monotherapy only 2 major cytogenetic responses could be registered. No severe adverse effects were observed. The first results suggest that the ATRA + interferon combination may be superior in achieving cytogenetic remission in the first chronic phase of CML. PMID- 11766236 TI - [First attempts in preimplantation genetic diagnosis: blastomere biopsy]. AB - There is an increasing expectation from couples that serious inherited diseases should be recognized at the earliest stages of embryonic development. A valuable tool for early prenatal diagnosis, preimplantation genetic diagnosis (PGD), involves the removal of 1 or 2 blastomeres from an in vitro fertilized embryo with micromanipulator (blastomere biopsy) without affecting the viability of the embryo. Genetic analysis of the removed blastomeres is performed to determine whether the embryo carries the genes responsible for the examined disease. Based on the results of the genetic analysis it is possible to transfer only unaffected embryos to the uterus. In this study, the authors performed blastomere biopsy on 35 embryos at the 6-10 cells stage. A total of 104 blastomeres were analyzed. On follow-up, 64% of biopsied embryos were cleaved and 43% developed to the morula or blastocyst stage. The introduction of this new procedure into the field of assisted reproduction can provide an alternative for couples who do not want to give birth to children affected by a genetic disease but would reject induced abortion after a positive prenatal diagnosis. PMID- 11766238 TI - Current developments in anaesthesia and neuromuscular transmission. PMID- 11766237 TI - [By adhering to current practice guidelines, survival is improved in thyroid cancer (Review of 24 papers about thyroid cancer published in English by Hungarian investigators in the past 20 years)]. PMID- 11766239 TI - Pharmacoeconomics in anaesthesia: what are the issues? AB - Newer anaesthetic agents provide a faster onset, easier titration and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to demonstrate that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and/or their caretakers, or the completion of an additional case in the same operating session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labour-intensive [phase I] postanaesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource utilization. A delay in starting a case, or a prolonged turnover time between cases, can negate any cost savings related to the anaesthetist's choice of drugs. PMID- 11766240 TI - Anaesthesia research is important. AB - The purpose of this paper is to describe the impact of anaesthesia research on clinical practice. The evolution of neuromuscular blocking drugs from the laboratory to the operating room is used as an example. Particular emphasis is given to the pioneers whose vision made this possible: H. R. Griffith and G. E. Johnson; D. Savage, J. B. Stenlake and W. C. Bowman and J. Viby-Mogensen. Our challenge is to ensure the supply of clinical scientists for the future. PMID- 11766241 TI - Drug research today. AB - The aim of this paper is to provide an outline of the current developments in drug discovery. However, in doing so, it is important to put these developments into an historical perspective and to acknowledge the impact that the previous research effort has had on research in progress. PMID- 11766242 TI - Predictors of onset and offset of drug effect. AB - Anaesthesiologists administer a wide variety of drugs, including benzodiazepines, opioids, intravenous anaesthetic agents, volatile anaesthetic agents, muscle relaxants, local anaesthetics, and other drugs, especially those influencing the cardiovascular system. Sometimes a drug is chosen because of its better effect and/or side-effect profile. However, many of the drugs within each group have similar effect and/or side-effect profiles and differ mainly in their pharmacokinetics. The choice of one drug over another may then need to be based on differences in their pharmacokinetic profiles. Traditional predictors of onset of drug effect, such as time to a specified effect, are dose-dependent. Traditional predictors of offset of drug effect, such as 'terminal half-life', often have little clinical relevance. Newer descriptors offer significant advantages. The time to peak effect-site concentration is an informative dose independent descriptor of the onset of drug effect following an intravenous bolus dose. The relevant decrement time (for continuous measures of drug effect) and mean effect time (for binary measures of drug effect) build upon the context sensitive half-time concept, by considering the time required for the concentrations to decrease from one clinically relevant level of drug effect to another. PMID- 11766243 TI - Day care surgery. AB - In recent years, day surgery rates have risen in many countries in the world. In 1998-99, 65% of elective surgery was performed as day procedures in the UK and about 70% in the USA. The future has the potential for an increase in day surgery as less well-performing countries and hospitals catch up with the best, and new surgical, anaesthetic and analgesic techniques are introduced. Consolidation and development of best management practices are necessary for sustained day surgery development. PMID- 11766244 TI - Anaesthetic strategies towards developments in day care surgery. AB - Ambulatory surgery is growing worldwide. The challenge of providing anaesthesia for longer and more complex surgery in sicker and elderly patients is a reality. To maintain the safety and good outcomes of ambulatory anaesthesia, high-risk patients will need to be evaluated carefully. Anaesthetic techniques that use short-acting drugs and minimize postoperative morbidity and mortality should become the focus. Policies on management of postoperative pain, nausea, vomiting, voiding and discharge from hospital will maintain good outcome measures. PMID- 11766245 TI - An approach to quality management in anaesthesia: a focus on perioperative care and outcome. AB - Health care systems throughout the world are faced with continuously rising health care expenditure. In Germany, a fee per capita system will be introduced by 2003 to keep the budgets for hospital care within limits. As a result, numbers of hospital beds and hospitals will be cut in the coming years. On the other hand, more and more patients and health care providers are asking if they are really receiving an adequate value for their money in the treatment they receive. All this will have a strong impact on the anaesthesiologist's work and her/his perception of the different facets of quality. Quality has various aspects for the anaesthesiologist. The patient as a customer should not incur any detrimental effects after a surgical procedure, and is accompanied by the anaesthesiologist throughout the perioperative setting. The surgeon needs optimal conditions to perform a procedure. The hospital must balance equally costs and income; this requires optimal operating room utilization. Finally, health insurance companies and the government are responsible for covering the cost of treatment according to the quality of the care delivered. Quality assessment concerning structure, process and outcome has to take these demands into account. Continuous quality improvement in the spirit of Deming's 'plan-do-check-act cycle' has to be part of anaesthesiologist's everyday routine. In future, the traditional barriers between the specialities treating a patient will be disrupted when reimbursement for treatment is made according to quality and efficacy of treatment. PMID- 11766246 TI - Muscle relaxants suitable for day case surgery. AB - Neuromuscular blocking agents are used as adjuvants in day case anaesthesia to facilitate tracheal intubation and/or surgery. Although the majority of day case procedures are performed without the use of neuromuscular blocking agents, there are procedures, such as laparoscopic surgery, microsurgery, open eye surgery, some ear, nose and throat procedures and some paediatric procedures, which may require neuromuscular blockade. The characteristics of an ideal neuromuscular blocking agent for day case surgery are a short onset, a short clinical duration and a short recovery time, with or without reversal. It should also lack histamine release, provide haemodynamic stability, and be competitively priced. This paper reviews the neuromuscular blocking agents currently available and used, such as succinylcholine and mivacurium, low doses of an intermediate-acting neuromuscular block, such as rocuronium and the recently introduced rapacuronium. Their advantages and disadvantages are described and discussed, with special reference to the needs of day case surgery. Rapacuronium offers certain benefits compared with the currently available neuromuscular blocking agents for day care anaesthesia. PMID- 11766247 TI - Muscle relaxants in paediatric day case surgery. AB - It has been estimated that more than 60% of all paediatric surgery is performed on a day case basis. The benefits of this type of surgery in children include reduced costs, avoidance of the stress of hospitalization and less disruption to family life. The growth of day surgery in children has been facilitated by the development of non-depolarizing neuromuscular blocking agents characterized by short and intermediate duration of action and fewer side-effects. The more rapid onset and shorter duration of action of non-depolarizing neuromuscular blocking agents in children should facilitate the use of these agents in place of succinylcholine for day case procedures. PMID- 11766248 TI - Use of reversal agents in day care procedures (with special reference to postoperative nausea and vomiting). AB - There is some confusion about the contribution of reversal of residual paralysis to the occurrence of postoperative nausea and vomiting. The aim of this review is to discuss whether antagonism of residual paralysis is a cause of postoperative nausea and vomiting, and to assess the risk of residual paralysis if the reversal is omitted. Data from a meta-analysis published before 1998 were considered, along with trials published after that date to assess the influence of reversal of residual paralysis on postoperative nausea and vomiting, and the likelihood of harm when antagonism was omitted. Moreover, an overview of pathophysiological consequences, incidence and clinical consequences of residual paralysis is given and the actual criteria of the adequacy of neuromuscular recovery presented. When emetic outcomes are combined across all trials and all different neostigmine doses, there is no beneficial effect from omitting neostigmine on postoperative nausea and vomiting, but there is some evidence of a dose-responsiveness with neostigmine; higher doses may have emetic properties. However, omitting reversal introduces a non-negligent risk of residual paralysis. An improved understanding of the pathological consequences of residual paralysis (i.e. impaired laryngeal and pharyngeal muscle function, alterations in hypoxic ventilatory control, reduced margin of safety) led to establishment of more rigorous criteria for defining adequacy of neuromuscular recovery. A train-of-four ratio of > or = 0.9 is now accepted as the index of adequate recovery of neuromuscular function. Applying this new definition, residual paralysis becomes a frequent adverse side effect. Neuromuscular recovery should therefore be routinely monitored in ambulatory patients and residual paralysis prevented by reversing neuromuscular block. PMID- 11766249 TI - A practical clinical approach to management of the difficult airway. AB - Difficult airway management represents a challenge in anaesthesia. In the last decades airway difficulty awareness has improved as a result of better anticipation and decision-making. Airway algorithms and protocols have a more prominent role in training and in clinical anaesthesia practice. In addition, several new instruments and therefore new techniques have been developed. These have improved possibilities for the clinician to secure the airway. Clinicians should become familiar with this equipment and techniques by using them on a regular basis in elective cases. The instruments available must be selected by the characteristics of the patient population, the local circumstances and the experience of the anaesthesiologist. The aim of this paper is to provide some practical guidelines with respect to airway difficulty predictors and airway instrument choice. PMID- 11766250 TI - Choice of the hypnotic and the opioid for rapid-sequence induction. AB - The choice of hypnotics and opioids for rapid-sequence induction, and the use of premedication, is influenced by the choice of the muscle relaxant. Anaesthetic agents have a major influence on the quality of intubation when rapid-sequence induction is achieved without a muscle relaxant. Premedication is important, along with a high dose of propofol (2.5 mg kg-1 or more) and a short-acting opioid such as alfentanil (30-40 micrograms kg-1) or remifentanil (up to 4 micrograms kg-1). It has also been demonstrated that i.v. lidocaine can improve intubating conditions. When a muscle relaxant is used, the choice of the anaesthetic agents depends on the onset of action of the relaxant. With a rapid acting compound such as rocuronium at a dose of 0.6 mg kg-1, the hypnotic agents need to be supplemented with only a small dose of opioids, e.g. alfentanil 10-20 micrograms kg-1. When succinylcholine, rocuronium 1.0 mg kg-1 or rapacuronium 1.5 mg kg-1 are used, excellent intubating conditions may be obtained by relatively smaller doses of hypnotic agents even without opioids; however, haemodynamic and intraocular pressure changes are better controlled when small doses of opioids are administered. PMID- 11766251 TI - Choice of the muscle relaxant for rapid-sequence induction. AB - Muscle relaxants are given as part of a rapid-sequence induction to facilitate tracheal intubation. Among all the muscle relaxants available, succinylcholine is the only one with a fast (approximately equal to 1 min) onset and a fast recovery. Therefore it is still the most frequently used muscle relaxant for rapid-sequence induction despite its well-known side-effects. The short duration of action of succinylcholine is, however, no substitute for aggressive airway management in the case of an unexpectedly difficult intubation in order to prevent life-threatening hypoxia. A preoperative assessment of the airway is mandatory in any patient and may indicate the need for using intubation techniques without a muscle relaxant. Rocuronium in large doses (i.e. > or = 1 mg kg-1) is an alternative to succinylcholine in a classical rapid-sequence setting under relatively light anaesthesia. With respect to rapid tracheal intubation, the timing and priming principles offer little advantage over the use of rocuronium in doses of 0.6 mg kg-1 in combination with an appropriate induction technique (i.e. including an opioid) or over the use of larger doses of rocuronium (> or = 1.0 mg kg-1) under relatively light anaesthesia, and may even be potentially harmful. In contrast to rocuronium, the use of rapacuronium in a rapid-sequence setting has been associated with dose-dependent respiratory side effects that limit its usefulness in doses higher than 1.5 mg kg-1 for this indication. PMID- 11766252 TI - Rapacuronium: clinical pharmacology. AB - The need for a rapid-acting non-depolarizing neuromuscular blocking agent with a short duration of action resulted in the synthesis of rapacuronium. The onset of maximum block with rapacuronium occurs in 60-90 s with doses of 1.5-2.5 mg kg-1 with a duration of clinical relaxation of 15-30 min. Rapacuronium provides clinically acceptable intubating conditions in 60 s in a majority of patients with these doses, although the conditions are somewhat inferior to those obtained with succinylcholine in lightly anaesthetized patients, such as those undergoing a rapid-sequence induction. The main drawbacks of rapacuronium are the occurrence of dose-related pulmonary side-effects (increased airway pressure and/or overt bronchospasm) and hypotension and tachycardia. The cause of pulmonary side effects is not certain but these have been serious enough to make its worldwide introduction doubtful. PMID- 11766253 TI - A pharmacokinetic-dynamic explanation of the rapid onset-offset of rapacuronium. AB - The rapid onset and offset of rapacuronium can be explained from its pharmacokinetic and pharmacodynamic characteristics. A unique property of rapacuronium is its high value for ke0, indicating a rapid access to the receptor site. The reason for this high ke0 may be related to the low intrinsic potency of rapacuronium, but this is not yet fully clarified. PMID- 11766254 TI - Rapacuronium: first experience in clinical practice. AB - Rapacuronium is a new non-depolarizing relaxant with a fast onset and rapid recovery. It was approved for the market in the United States in August 1999. The reasons for its acceptance in practice and the niche it fills are the subject of this review. Rapacuronium has been accepted wherever rapid onset and short duration of action are advantageous. It has received the greatest acceptance in brief outpatient procedures that require tracheal intubation. The average time of recovery to a train-of-four ratio of 80% is about 25 min after a usual intubating dose of 1.5 mg kg-1, when block is reversed. Its rapid onset has led some to use it in rapid-sequence induction, but the exact place in this scenario is still being defined. Its spontaneous recovery is rapid enough that many practitioners do not reverse the block if the procedure is long enough. Data suggest that this is reasonable after 60 min and may even be earlier, even 30 min, if verified by monitoring. The main adverse effects of rapacuronium are bronchospasm, hypotension and tachycardia. Of these, only bronchospasm has had significant clinical impact. These effects are dose related and the recommended dose of 1.5 mg kg-1 may keep problems to a minimum. Because rapacuronium is a new drug with unique properties its use gradually increased in its first year. Because of the problems associated with succinylcholine, rapacuronium may have advantages for brief outpatient procedures and in cases where rapid termination of block is desired, provided its adverse effects can be minimized. PMID- 11766255 TI - [Perspectives for the proteome research. Will university and academic science survive in competition with commercial firms?]. PMID- 11766256 TI - [The role of hyperlactatedehydrogenasemia in induction of metabolic disorders in the body]. AB - The effect of intravenous administration of lactate dehydrogenase (5000 E/kg) on some metabolic parameters was investigated. The hyperenzymemia was accompanied by changes of metabolite content (glutamate, 2-oxoglutarate, lactate, dihydroxyacetone phosphate) and enzyme activities (aldolase, lactate dehydrogenase, transaminase) in heart, liver and skeletal muscles. Intravenously administered tritiated lactate dehydrogenase was preferentially found in skeletal muscles, liver, kidneys and some other organs. PMID- 11766257 TI - [Sensitivity of E. coli and C. freundii strains to 5-azacytidine]. AB - The sensitivity of E. coli and C. freundii strains to 5-azacytidine and restrictase activity of partially purified cell-free extracts were investigated. Restrictase activity was found only in 5-azacytidine-sensitive strains. In the 5 azacytidine-resistant strains restrictase activity was not detected. PMID- 11766258 TI - [Effect of antioxidant histochrome preparation on the contractile function and metabolism of the isolated rat heart under conditions of "calcium paradox", ischemia, and reperfusion]. AB - A comparative study of protective effect of a new antioxidant histochrome on isolated rat heart at calcium paradox and ischemia-reperfusion was carried out. Perfusion with Ca-containing solution after 10-min perfusion with Ca-free medium caused depletion of high energy phosphates, loss of myoglobin, uncoupling of mitochondria, increase of left ventricular diastolic pressure. Pretreatment with histochrome led to decrease of cardiomyocyte damage evaluated by myoglobin efflux in perfused solution, attenuation of decrease ATP and phosphocreatine, and coupling of mitochondria. This resulted in a decrease of left ventricular diastolic pressure at calcium paradox. Less effect of histochrome treatment was noted in the case of ischemia-reperfusion model. It was concluded that histochrome effectively prevents heart from abnormalities caused by calcium imbalance in heart. PMID- 11766260 TI - [Changes in biochemical characteristics of collagen and the cartilage water in osteoarthritis]. AB - The stability of collagen molecules and moisture capacity of human normal and osteoarthrotic (OA) cartilage were studied before and after extraction of glycosaminoglycans (GAG) by 4M guanidinum chloride. The content and nature of water were determined by Fisher titration, DSC and analysis of sorbtion desorbtion processes of water vapour in cartilage. The stability of collagen molecules was determined by the degree of enzymatic hydrolysis: collagenase, pronase and pepsin. It was found that weakening of bonds between main compounds of the cartilage matrix and decrease of GAG quantities in the OA cartilage were accompanied by structural disorganization of the collagen network, which is manifested by breakdowns of intramolecular bonds in telopeptides and intermolecular bonds in the spiral part of collagen molecules, these changes may contribute to increase of total water in OA cartilage. The correlation of free and bound water fractions in cartilage was increased from 5 to 44 in OA cartilage. These results can be used as a criterion of pathological condition of human articular cartilage. PMID- 11766259 TI - [Effects of mannose derivatives on development of selectin-dependent peritoneal inflammation in rats and mice]. AB - The inhibitory effect of mannose-containing oligosaccharides on model carbohydrate ligand interaction with E-, P- and L-selectins in vitro, as well as on the ability of these compounds to block the leukocyte extravasation in rat and mouse peritonitis in vivo was studied. The monomeric and polymeric compounds, 4 nitrophenylthiomannoside, phenylmannoside, conjugated with polyacrylic acid, and alpha-mannose, conjugated with polyacrylamide, inhibited the binding of the model ligand to P- and L-selectins (but not to E-selectin). Intravenous injection of these compounds was found to cause a dose-dependent reduction of neutrophil accumulation in rat peritoneum. The polysaccharide mannan was inactive in both types of experiments. The conjugate of phenylmannoside with polyacrylic acid was the most effective blocker as in vitro experiments, as well as in vivo. The inhibitory effect of subcutaneous injection of 4-nitrophenylthiomannoside on mouse peritonitis was demonstrated. PMID- 11766261 TI - [Reductase activity in the liver microsomes in adult and old rats during immobilization stress]. AB - The activity of NADH: and NAD(P)H:2,6-dichlorphenolindophenol reductases was investigated in liver microsomes of adult and old rats during immobilizing stress. There significant decrease of both reductases was found in old animals. Pronounced decrease of NADH:2,6-dichlorphenolindophenol reductase activity was found in adult immobilized rats. PMID- 11766262 TI - [Lipids of the bone tissue in bodies of thoracic vertebrae in scoliosis in rabbits]. AB - The content of total lipids, triglycerides, cholesterol and phospholipids in the bone tissue of the bodies of the thoracic vertebrae was investigated in 4.5-, 7- and 12 month old rabbity. The development of scoliosis in two month old animals was induced by the one-sided blockade of the afferent links of the innervation in thoracic region at the extent of four segments (TH6-9). In: experimental scoliosis there were important alternations in the content of the total lipids comparing with the control which are observed only on the level of the primary and of the anterior compensatory curves in 12 months old animals. The content of triglycerides changed even at early stages of the development of scoliosis. A decrease of triglycerides content was observed at the level of the primary curve in rabbits of all ages with experimental scoliosis. Probably it is due to the alteration of neurotrophic processes in the bone tissue. There were similar age related changes of triglyceride content in both groups of animals. Phospholipids have absolutely another than triglycerides dynamics of the content changes during the scoliosis development. Time-course of phospholipid changes in scoliosis differed from that of triglycerides. In older rabbits with experimental scoliosis the cholesterol content in the bone tissue of vertebral bodies was reduced by 1.5 2 times while in normal animals it remained almost unchanged. The most substantial changes in cholesterol content of the vertebral bone tissue in rabbits with the experimental scoliosis occur in early age (4.5 months) on the level of the primary curve and the posterior compensatory curve. This may be considered as one of the biochemical indicators of the progressing scoliosis. PMID- 11766263 TI - [Antioxidant effect of novel probucol analogs and their combinations with alpha tocopherol]. AB - The antioxidant and antiradical activities of sulfur containing phenols which are analogues of probucol in comparison with alpha-tocopherol and BHT were tested using initiated methyl oleate oxidation model. The antioxidant effect linearly increased with increasing concentration of phenols. The ability of investigated phenols to destroy and reduced accumulation of hydroperoxides is revealed. The combined inhibitory effects of composition most effective researched antioxidant- CO-3--with alpha-tocopherol for the first time are described. PMID- 11766264 TI - [Interaction of heparin with amino group-containing materials]. AB - The influence of the glass surface immobilized aminogroups nature and the experiments conditions on the interactions between heparin and aminogroups containing surface was studied using total internal reflections fluorescence. It was shown, that the nature of the terminating aminogroup, but not its mobility or the amount of the aminogroups in the main chain, is the major factor influencing the heparin adsorbtion from individual solution. Both the nature of terminating aminogroup and its mobility determine heparin adsorption on the aminogroups containing surfaces from the blood plasma proteins containing solution. Heparin irreversibly adsorbed from individual solution is not replaced by blood plasma proteins. The tertiary aminogroups containing surface adsorbs maximal quantity of the heparin. PMID- 11766265 TI - [Hypermethylation of the human calcitonin gene as a molecular marker in acute lymphoid leukemia]. AB - HpaII/MspI blot-hybridization analysis of the 5'-end region of the calcitonin (CT) gene methylation in cells of bone marrow and peripheral blood of patients with acute lymphoblastic leukemias (ALL) has been carried out. ALLs are accompanied by hypermethylation of the inner cytosine in the CCGG sequences of this region of the CT gene. The level of hypermethylation of the CT gene corresponded to the degree of disease progression and malignancy. At a long-term remission, hypermethylation of the CT gene is not observed. In case of primary resistance or if the complete remission has not been achieved the CT gene remained hypermethylated. It has been shown that in relapse the normal CT gene methylation pattern reversed to hypermethylation. This phenomenon was detected 1 8 months before the obvious clinical and laboratory signs of the disease progression (relapse). The large size of abnormal HpaII-fragments of the 5'-end region of the calcitonin gene had a direct correlation with the malignancy status of ALL. PMID- 11766266 TI - [Level of autoantibodies to opiate receptors in blood of patients with opiate addiction]. AB - The level of autoantibodies to opiate receptors was measured in serum of heroin addicts in withdrawal and in the period of long-term abstinence and in healthy volunteers as well. The level of autoantibodies was assessed with ELISA with synthetic peptide specific for subregions of mu and delta opiate receptors. The scores of the level of autoantibodies higher than 150% of the level noted in healthy volunteers was observed in 56% of heroin addicts. The dependence of autoantibodies level from duration of diseases was shown. Elevated level of opiate receptors autoantibodies were detected in the sera of 71% patients with opiate addiction who had been using heroin more then one year. High levels of opiate receptors autoantibodies were observed more frequently in patients with opiate withdrawal syndrome then in patients with long-term remission. Elevated level autoantibodies to opiate receptors were determined in the blood of 38% opiate abusers with remission for 3-8 months. The level of autoantibodies to opiate receptors may be used for diagnostics of heroin dependence and control of treatment efficiency. PMID- 11766267 TI - Some thyrotropic agents. PMID- 11766268 TI - [Probiotics--possibilities and limitations of their application in food, animal feed, and in pharmaceutical preparations for men and animals]. AB - Probiotics are cultures of special microorganisms, which have been used as feed additives since the seventies of the past century and already since the twenties in food specimen and in pharmaceuticals. The definition of "Probioticum" was formulated in 1974 simultaneously with the use of living cultures in feed for various animals in order to substitute the application of nutritive antibiotics or chemotherapeutics. In the meantime probiotics are applied not only as feed supplements or pharmaceuticals but increasingly in suitable food specimens such as dairy products, fruit juices, chocolates, and even meat products. Of course, heating of such products prior to consumption or application must be ruled out. The selection of a suitable strain of a microorganism can be regarded as the primary requirement for the use as a probiotic. These cultures must be able to pass the stomach-duodenum barrier in a viable state and to multiply at the site of destination in the intestine. Additionally, they must be capable of producing antagonistic metabolites against a dominating saprophytic microflora resulting in a competitive growth. These abilities are common among lactic acid bacteria, e.g. lactobacilli and bifidobacteria. Yet, intended autochthonous species do not possess very good technological features for the enrichment in food specimens, because their viability will decrease rapidly under unfavourable conditions as it is the case with mineral supplements in feed or with low acidity in fermented dairy products. Therefore, some other microorganisms like spore-forming species or yeast cultures were introduced as probiotic components. These possess some similar features which render them suitable for probiotic use. But their physiological and ecological traits do not qualify them as probiotics of first choice. The special efficacy of probiotics must be strictly verified in animal nutrition due to restrictive EC-regulations, in pharmacy due to legal restraints, and in food applications in accordance with food law regulations. Safety aspects are considered very restrictively in feed applications, in the food and pharmaceutical sector they should be in accordance with the intended purpose of "fulfilling health claims". In the presented review the different requirements for the application of probiotics in animal nutrition, in food, and in pharmaceuticals will be provided. The special effect of competitive exclusion of pathogenetic and toxinogenic microorganisms in fowl performance are mentioned and even the application of probiotics as marine aquacultures of fish and Crustaceae will be included. Furthermore, the safety aspects resulting from the tremendous amount of industrially produced cultures which are distributed into the environment will be discussed. In conclusion it may be pointed out that probiotics may serve to partially replace the presently reduced or even prohibited application of nutritive antibiotics or chemotherapeutics in animal nutrition and in fulfillment of health claims in man and animals. Economic and environmental aspects will reduce the overall application of probiotics world wide. Restrictions of use and controls of efficacy and safety are essential and must be implemented periodically. PMID- 11766269 TI - [Zoonoses control--new challenges in health protection of consumers]. AB - The eradication of bovine tuberculosis and brucellosis of domestic stock in Germany through the combined efforts of veterinary medicine, the agricultural section and the state was an historic achievement. Since the two diseases are zoonoses, their successful control can also be seen as a valuable contribution to public health. Both these zoonoses are classic animal diseases presenting themselves as clinical entities complete with gross pathological lesions. In contrast, today we are confronted with pathogens causing zoonoses characterised by latent, i.e. clinically inapparent herd infections that do not result in visible tissue changes. Nevertheless, through contaminated foodstuffs, these pathogens contribute to food-borne infections leading to the outbreak of genuine zoonoses in humans. It has been estimated that there could be as many as two million cases of food-borne infections annually in Germany. Among them are salmonellosis, campylobacteriosis, yersiniosis, infections with verotoxin producing E. coli, listeriosis and toxoplasmosis. While the national animal disease legislation only foresees the control of notifiable diseases, the basis for zoonoses control is laid down in the EU Zoonosis-Directive, which is presently awaiting its transposition into national law and into practice. In order, for instance, to combat the most important Salmonella infections of humans, Integrated Quality Systems (IQS) have been formulated as a means of implementing the proven HACCP concept in animal production units and ensuring animal health from the point of view of consumer protection. The aim of all measures must be to free infected herds of pathogens, to investigate and eliminate all sources with a potential for further pathogen introductions, to maintain pathogen-free herds--with a reduced pathogen challenge in mid-term time periods--, as well as to develop diagnostics capable of identifying pathogen carriers before slaughter. For the disinfection of stock, it is important to have epidemiological data collecting systems and information systems that allow complete diagnostic tracing from herd to slaughterhouse and vice versa. All sides, including research and surveillance, as well as producers are called upon to actively share in protecting the health of consumers as far as it is threatened by latent infections in domestic stock. PMID- 11766270 TI - [Fundamental safety requirements in the use of live vaccine in food animals]. AB - Live vaccines have a number of advantages over inactivated ones--above all in respect of the stimulation of cell-mediated immune reactions. Various live vaccines, based on viruses, bacteria, fungi or parasites, have been approved for use in Germany in animals used as a source of food. Safety requirements obviously play a more important role for live vaccines, both in vaccine development and in batch testing, than with inactivated vaccines. Vaccine strains isolated from tissue samples must be clearly distinguishable from field strains. The safety of overdoses and the spread of the vaccine strain in the immunized animals have to be investigated, as well as shedding of the vaccine strain and its safety in non target species. Any impact of a live vaccine strain on humans and the environment must be assessed. Live vaccines will remain an important research field in the long term, with efforts focused on developing deletion mutants and vector vaccines. PMID- 11766271 TI - [Laboratory-based surveillance of salmonellosis of humans in Germany--safety of Salmonella typhimurium and Salmonella enteritidis live vaccines]. AB - The Paul Ehrlich Institute, Langen, in Germany has been licensed different live vaccines of S. Typhimurium and S. Enteritidis for use in the veterinary medicine since I the 90s. The Robert Koch Institute has established a lab-based surveillance system for these live vaccine strains for an evaluation of recent public health safety. Since 2000 all strains of S. Typhimurium and S. Enteritidis from humans were investigated in respect to their phage types and other vaccine markers. 3676 S. Typhimurium strains and 4489 S. Enteritidis strains mainly from Salmonellose patients were investigated after phage typing according to their auxotrophic or antibiotic resistance markers. The live vaccine strains of Zoosaloral, TAD Salmonella vacT or TAD Salmonella vacE and Salmovac SE could not be found from infections in humans. PMID- 11766272 TI - [Food animal surveillance: search for a safe system?]. AB - In Europe, meat inspection procedures have been established in the course of the last century. Techniques at that time available were used. This traditional approach has been taken over with the regularisation in the EEC. However, in order to scrutinise this approach as well as to specify modern tasks of meat inspection, a scientific and more basic approach is required and could read as follows: Pointing out the tasks of meat inspection as wanted by the specific society (human health, animal health and welfare as well as a certain quality level of the product). Collecting of particular criteria in order to ensure every task mentioned above. This could be addressed by use of a system based on the principles of Risk Analysis (identification and characterisation of a hazard (or unwanted item), consumer's exposure assessment). Having deduced the required criteria, for each of them an appropriate method must be available. Only then an overall system might be suggested, and only then particular techniques might be discussed. From examples is concluded, that the technical performance of meat inspection must be re-evaluated. Presently a total concept is not available. PMID- 11766273 TI - An approach towards public health and foodborne human listeriosis--the Austrian Listeria monitoring. AB - The Institute for Milk Hygiene, Milk Technology and Food Science has launched a Listeria monitoring for Austrian cheese factories in 1988 which is nowadays a valuable tool to control the safety of cheese production. It is a means to qualify the proper hygienic conditions in the participating cheese plants. Proper hygiene protects cheese plants from getting contaminated by L. monocytogenes. The preventive elimination of foodborne pathogens facilitates a thriving economical development of the domestic cheese industry as contamination by L. monocytogenes may lead to a stop of delivery, product recall and other costly measures. This report comprehensively describes the principle of the monitoring including a description of the microbiological and molecular tools. It summarizes data on the detection frequency of Listeria contamination with respect to the different matrices under investigation. Furthermore an overview is given on the course of 17 contamination periods in 10 cheese plants and the outcome of the decontamination endeavours is described. Apart from epidemiological investigations, this report summarizes data regarding molecular species confirmation in the genus Listeria as the species assignment was comparatively examined by both conventional microbiology and molecular tools. Genotyping by Pulsed Field Gel Electrophoresis was applied in three plants which were confronted with a long term contamination period. The data presented in this paper rely on results which were collected through a decade of investigation (1990-2000). PMID- 11766274 TI - [Comparison of direct colony count methods and the MPN-method for quantitative detection of Listeria in model and field conditions]. AB - In order to compare the plate count method for quantitating Listeria, as published in the "Official Collection of Testing Methods" in section 35 LMBG (L. 00.00-22), to an MPN-method for Listeria based on the same mediums, these two detection methods for Listeria were tested in three sets of experiments and a routine sample status evaluation. A pure broth culture of L. monocytogenes, artificially with L. monocytogenes contaminated ground meat, artificially contaminated and cold stored ground meat as well as 77 ground beef samples from Berlin retail food stores were used in the four trials. The detection limit of the MPN-method is about 66% lower than the plate count method allowing detection of a clearly greater number of Listeria-positive samples from naturally contaminated ground meat. The MPN-method yielded more Listeria spp.-positive samples (rel. 43%) and more L. monocytogenes-positive samples (rel. 21%) versus the colony count method based on the results from the field trial using ground beef samples from retail food stores in Berlin. Nevertheless the standardized colony count method is preferred over the MPN-method for routine use because of its slightly higher productivity and much smaller variation in the results. However, the MPN-method is preferable for epidemiological studies because of the significance of the lower detection level. The random sampling evaluation of ground beef from retail stores indicated that 39% of the samples were Listeria spp.-positive and 31% were L. monocytogenes-positive when using the colony count method. A total of 56% of the meat samples were found to be Listeria spp. positive and 38% L. monocytogenes-positive when the MPN-method was used. Population levels ranged from 10 to 580 cfu/g (Listeria spp.-positive samples) and from 10 to 270 cfu/g (L. monocytogenes-positive samples) for the colony count method. The MPN-method yielded population levels of 3.6 to 930 MPN/g for Listeria spp.-positive samples and 3.6 to 150 MPN/g for L. monocytogenes-positive samples. L. monocytogenes strains isolated using the colony count method belonged to the following serovars: 1/2a (46%), 1/2b (13%), 1/2c (33%), 3b (4%) and 4c (4%). A similar serovar isolation pattern was found for L. monocytogenes-positive MPN tubes. The most common serotype was 1/2a (43%), followed by 1/2c (32%) and 1/2b (14%). The serotypes 3c, 4b and 4c were all isolated 4% of the time. PMID- 11766275 TI - [Sampling plans in microbiological criteria for food and their "performance criteria"]. AB - Statistically based acceptance sampling plans have been integrated into microbiological criteria for food in international trade for some time. Especially two- and three-class sampling plans for attributes are used, variables plans are applied less. A lot of examples can be found in the so-called ICMSF (International Commission on Microbiological Specifications for Foods) "sampling book" or in EU guidelines. However, quite often the required confidence and the assumptions on tolerable lot qualities on which the choice and design of sampling plans are based can't be deduced from such recommendations and prescriptions. These problems have led to critical discussion of the performance of two- and three-class sampling plans used in microbiological criteria, showing complex dependencies on microbiological limits and on the expected variability of sampling results. As a result means should be considered to use knowledge gained from process analyses in food production in the design of sampling plans. In this context the performance of acceptance sampling plans as prescribed in microbiological criteria for foods will be discussed as well as their role in recently developed food safety concepts. PMID- 11766276 TI - [Comparison of the two different PCR assays for the detection of thermotolerant Campylobacter in poultry]. AB - In this study two PCR-assays were compared for there suitability in routine food examination. The rapid and sensitive seminested PCR assay of Wegmueller et al. (1993) provides a useful tool for specific detection of thermotolerant Campylobacter spp. in poultry. For laboratories, which have not established hybridisation technique yet, the seminested PCR assay fulfills the necessity to verify the amplicons (Anonymous, 1998 a) and provides therefore an alternative to the published provisional method according to section 35 LMBG (Anonymous, 2000). The results clearly show that the pg50/pg3-PCR assay (Oyofo et al., 1992) isn't a useful screening method because there is a strong necessity to verify the obtained amplicons by southernblot-hybridization in order to increase sensitivity and specificity. To avoid false-negative results extern amplification controls are reliable tools. The commercially available DNA-Extraction kit used in this study facilitates rapid and effective extraction of bacterial DNA out of food matrix. PMID- 11766277 TI - [Detection and characterization of verocytoxin-producing Escherichia coli types (VTEC) from different sources]. AB - Hemolytic uremic syndrome (HUS) is caused by enterohemorrhagic E. coli (EHEC) belonging to a few serovars embracing strains of O26, O103, O111, O118, O145 and O157 serogroup, respectively. In own investigations 3.791 food specimen of animal origin were investigated by use of an enzyme-immuno-assay (EIA) and the polymerase chain reaction (PCR). All E. coli isolates (n = 459) of food as well as isolates from cattle feces (n = 440), from HUS patients (n = 50) and asymptomatic human carriers (n = 16) were investigated by means of the PCR using primer pairs for verocytotoxin genes (vtx1, vtx2, vtx2c, vtx2d, vtx2e), the E. coli attaching und effacing gene (eae), the enterohemolysin-gene (ehlyA) and the vt2 transporter protein-gene (ile X tRNA). Differences were found in respect to the eae- and the ile X tRNA genes, which could be detected in significantly higher ratios in the isolates from patients and human carriers. Furthermore vtx2d strains were exclusively analyzed to each 25% in food and cattle strains. In six food samples pathogenic strains of serovar O157 were detected whereas some of the cattle strains were estimated to belong to EHEC serovars O26:H11, O118:H- and O157:H7. The own data support the thesis that the risk for human beings is affiliated to a great extent by direct contact with ruminants, followed by person to-person transmission. Regarding the epidemiological data the thesis that each VTEC strain ist potentially an EHEC strain can not longer be substantiated. PMID- 11766278 TI - [Controversies about Barrett esophagus]. PMID- 11766279 TI - [Specific mortality rates by DRG and main diagnosis according to CIE-9-MC at a level-II hospital]. AB - INTRODUCTION: The in hospital mortality is a marker of health care quality. It can be evaluated according by the principal diagnosis of disease or by Diagnosis Related Groups (DRG). OBJECTIVES: Know and to analyze the in hospital mortality and mortality rate (MR) in the patients admitted in the Hospital Morales Meseguer (Murcia) of II level of the INSALUD during 1999. METHODOLOGY: Study of the minimum basic group of data into the hospital. RESULTS: The MR was 3.8% of 508 deaths analyzes, 56.7% corresponded a male. The MR was equal in male (3.6%) and females (3.9%). The medium of age into deaths was 77 years. The numbers of deaths inpatients under 80 years was higher in males (n = 197; 65%) than in lower in female (n = 102; 35%)(p = 0.002). The addition of deaths of Internal Medicine and Intensive Care Unit represent a 70% of cases of deaths occurred in the hospital. The MR was higher in Intensive Care Unit (10.5%) followed by Hematology (6.9%) and Internal Medicine (6.1%). Ten DRG represents of 50% of the causes of deaths, and all of them were DRG of medical categories. The DRG more frequents was 541, Respiratory disorders with complication (n = 61, MR 12.8%), followed by DRG 533. Specific cerebrovascular disorders without Transit isquemic accident (n = 33; MR 34.7%), DRG 123 Acute myocardical infarction (AMI) with death (n = 31; MR 100%), DRG 014 Others disorders of nervous system (n = 27; TM: 10.3%) y DRG 552 Disorders of digestive tract without esophagitis, gastroenteritis and not complicated ulcer (n = 27; MR: 31.0). The main diagnostic more frequent was cerebrovascular diseases (n = 60, MR 12.2%), pneumonia-bronchopneumonia (n = 52, MR 10.9%), chronic obstructive lung disease (n = 36, MR 7.1%), AMI (n = 33, MR 11.5%), and neoplasia of digestive tract (n = 26; MR 8.5%). The MR of woman with AMI (19.5%) was higher than man (7.7%) (p = 0.005), the MR in woman with abdominal hernia (4.3%) was higher than man (0.6%) (p = 0.01), and MR of pyelonephritis and urinary infection in man (4.9%) was higher than woman (0%) (p = 0.008). CONCLUSIONS: The mortality and MR by DRG and main diagnostic is an indicator than permit to know and monitoring the quality of health care. PMID- 11766281 TI - [Pneumothorax in patients infected by the human immunodeficiency virus]. AB - OBJECTIVE: Patients with HIV who develop pneumothorax have been previously described. Pneumocystis carinii pneumonia (PCN) is the leading cause of this complication, but infection by other pulmonary microorganism, inhaled pentamidine therapy and lung invasive manoeuvres have also been associated with pneumothorax in HIV infected patients. METHOD: We review the most relevant clinical aspects of pneumothorax in HIV-infected persons, gathered in our hospital along eight years, before HAART therapy was started. During this time, 97 patients with PCN were diagnosed and 148 patients received prophylaxis with inhaled pentamidine. Only 14 episodes of pneumothorax in 13 patients, were recorded. In ten occasions pneumothorax was related to pulmonary invasive manoeuvres, pulmonary infections were found in three and was considered spontaneous in one. The pulmonary invasive manoeuvres were: subclavia vein catheterisation in six cases (one of them was diagnosed of proved PCN and the other has pneumococcal pneumonia); transbronchial biopsy in one patient (also with proved PCN), knife chest trauma in two cases and after fine needle aspiration of an axillary lymph node in one patient. RESULTS: The pulmonary infections associated with pneumothorax in three patients were: proved PCN (this patient was the only one in the group with inhaled pentamidine prophylaxis who developed pneumothorax), active pulmonary infection by mycobacterium tuberculosis and Pseudomonas aeruginosa pneumonia. A drainage chest tube was placed in 12 patients with complete resolution in nine. In the other two patients pleurodesis was necessary and surgical repair was carried out in the other one (who had pulmonary tuberculosis). During the follow up six patients died (median time to death: 7 months). Among patients who died, five had pulmonary infections when the pneumothorax was diagnosed: PCN in three cases, pulmonary tuberculosis and pseudomonas pneumonia in the other two; all of them with less than 100 CD4 lymphocytes. CONCLUSIONS: Pneumothorax is frequent in HIV infected patients with PCN, but other lung infections and, above all pulmonary invasive manoeuvres, can cause this complication. In our experience, HIV-infected patients who develop pneumothorax have a bad prognosis. PMID- 11766280 TI - [Survival and disease progression in 251 patients with HIV-1 infection. Study of p24 antigen and viral burden as prognosis makers. Their value at 4 years of follow-up]. AB - BACKGROUND: Prospective study of survival and AIDS or death progression in a cohort of 251 HIV infected patients whose seroconversion time is unknown, with a main objective: To analyse p24 antigen plasmatic levels and viral load as surrogate markers. PATIENTS: 251 patients were included, most of them undergoing antiretroviral therapy, and were followed-up consecutively in the HIV/AIDS Unity of Internal Medicine Service of the Hospital Universitario Arnau de Vilanova in Lleida. METHODS: We made clinical and analytical baseline studies and every 3 months thereafter. Related to p24 antigen 3 group were established: group I, < 20 pg/mL, group 2, 20-39 pg/mL, group 3, 40 or more pg/mL. We studied survival and progression according to baseline levels over 4 year period. Regard to viral load, we just compared this with p24 antigen in the last phase of the study (third and fourth year) for technical reasons. Survival analysis was made by Kaplan-Meier estimation. Relative risk was calculated by Cox's proportional hazards model. RESULTS: During the 48 months of follow-up 55 patients died. AIDS progression risk or death was 4.8 times higher for the p24 antigen > = 40 pg/mL group than for the p24 antigen < 20 pg/mL one; the relative risk of patients with p24 antigen between 20-39 pg/mL was 2.5 times higher than those included in the group of p24 antigen < 20 pg/mL. Related to progression study, 34 patients progressed. AIDS progression risk or death for p24 antigen > = 40 pg/mL group was 7.69 times higher compared with group 2 (p24 antigen levels between 20-39 pg/mL). The comparison with viral load by PCR determination shows controversial results. CONCLUSIONS: p24 antigen plasma level is a good survival and AIDS progress or death surrogate markers in HIV infected patients, and it is useful for 4 years or more. An isolated value < 20 pg/mL is a sign of good prognosis. Parallelism between p24 antigen plasmatic level and viral load has not been observed. PMID- 11766282 TI - [Thrombosis of the basilar artery and mechanical ventilation]. AB - BACKGROUND: To know the incidence, risk factors, complication and prognosis of the serious thrombosis of the basilar artery. METHODS: All patients diagnosed as having basilar thrombosis during a 10 year period (1/1/1989 to 31/12/1998) and having been connected to mechanical ventilation in our hospital are retrospectively revised. The following data are analysed: gender, age, risk factors, cause of intubation, days of stay at the intensive care unit and at the hospital, the prognosis at 3 and 6 months and the causes of decease. RESULTS: 62.5% of the 24 found cases were males. The average age among the survivors and the decreased was similar (60.1 +/- 16 and 62 +/- 15.8 years). The most common risk factors were high blood-pressure, atrial fibrillation, diabetes mellitus and smoking. The average stay at the intensive care unit was 11.2 +/- 14.8 days and 31.9 +/- 58.6 days at the hospital. The cause of intubation were: coma, airway protection, cardiorespiratory arrest, general convulsive crisis and respiratory infection. Mortality reached 75% and was caused by progression of coma or infections. Only 16% of them recovered satisfactorily. CONCLUSIONS: The patients admitted to hospital in coma, in revived cardiorespiratory arrest and those presenting general convulsive crisis or pneumonia have a higher mortality. Special attention must be drawn towards the appearance of hydrocephalus and infections due to the importance of an early treatment. In patient with a progressive damage of the consciousness level, the airway protection might improve the prognosis. PMID- 11766283 TI - [Community-acquired empyema caused by Acinetobacter baumannii]. AB - We referred a fourty-four years old male, without interesting personal history and who was accepted in the hospital due to dyspnea and fever and who was diagnosed with empyema by Acinetobacter baumannii acquired in the community; we have found no references about this in the medical literature. PMID- 11766284 TI - [Mediastinal malignant schwannoma in a patient without Von Recklinghausen disease]. AB - Malignant tumors of peripheral nerve sheath (malignant Schwannoma) arising in mediastinum are rare, principally in patients without Von Recklinghausen's disease been fever exceptional as symptom of presentation. We present a case of a woman without neurofibromatosis with a malignant Schwannoma in posterior mediastinum who present as fever of unknown origin, and we comment radiological, hystological and inmunnochemical features. PMID- 11766286 TI - [Treatment of Barrett esophagus in the XXI century: controversies and future perspectives]. AB - Barrett's esophagus is today, one of the digestive pathologies that raises more interest in all the meetings and congresses of the specialty, in spite of have been described 50 years ago. The definition has changed; the rising incidence of adenocarcinoma has been recognized; a most effective therapy to control gastroesophageal reflux has been developed (proton pump inhibitor v/s laparoscopic fundoplication); appropriate surveillance intervals of patients with dysplasia have been protocolized; new treatment strategies are being investigating. Although, numerous controversies still persist. The exact and accurate knowledge of physiopathology constitutes the base of treatment and prevention for gastroesophageal reflux disease and their complications. PMID- 11766285 TI - [Lung adenocarcinoma associated with myxoma of the right atrium]. AB - A 68 year-old man, was fond to have both an adenocarcinoma of the lung and a right atrial myxoma during a preoperative Dupuytren disease chest x-ray. The following case is being reported for to discuss diagnosis, to discuss management, for the feasible association between diseases and the few previous reports in the English-language literature. PMID- 11766287 TI - [Liver diseases and pregnancy]. AB - The pregnancy determines a deep variation in the human physiology mediated through sexual hormones. These changes can entail the appearance of diseases that affect the liver such as hyperemesis gravidarum, HELLP syndrome, intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy. The knowledge of the specific features of these diseases is crucial for their prompt recognition, since they are uncommon diseases in the clinical daily setting of the hepatologist. In addition, several preexisting chronic hepatopathies, including the liver post-transplant status, can affect the course of pregnancy and the maternal-fetal health. Understanding the distinct hepatic diseases which develop during pregnancy must be based on the knowledge of the perceptible physiological changes both on physical examination and laboratory tests which occur during the uneventful gestation. PMID- 11766288 TI - [Atelectasis secondary to bronchial carcinoid tumor]. PMID- 11766289 TI - [Acute cholecystitis, septic shock, and miliary tuberculosis]. PMID- 11766290 TI - [Hodgkin's disease with epitrochlear onset]. PMID- 11766291 TI - [Interstitial nephritis, autoimmune hemolytic anemia, and rifampicin]. PMID- 11766292 TI - [Pleural benign fibrous mesothelioma versus pleural benign solitary tumor]. PMID- 11766293 TI - [Endocarditis caused by unusual bacteria]. PMID- 11766294 TI - [Streptococcus pyogenes sepsis in a patient with Ki-1 anaplastic lymphoma]. PMID- 11766295 TI - [Temporal arteritis and dementia]. PMID- 11766296 TI - [Dermatologic manifestations as presentation form of autoimmune hepatitis]. PMID- 11766297 TI - [Spondylodiscitis in 3 children; differential diagnosis and treatment]. AB - Three children, a 4.5-year-old boy and two girls aged 21 months and 10 years respectively, had for several weeks to months experienced lower back pain or walking problems, two of them had an elevated sedimentation and leucocytosis. The MRI scan revealed a narrowing of the lumbal disk. Furthermore, in the case of the 10-year-old girl, Staphylococcus lugdunensis was cultured from the puncture material of the disk. After treatment she continued to experience intermittent complaints of back pain; the other children made a complete recovery. (Spondylo)discitis must be differentiated from vertebral osteomyelitis. In the case of (spondylo)discitis, immobilising the spine with a corset is the mainstay of treatment. Antibiotics are only indicated when osteomyelitis cannot be excluded. Generally, the prognosis is good. PMID- 11766298 TI - [Disaster medicine: lessons from Enschede and Volendam]. AB - Two major disasters hit the Netherlands recently: on May 13th 2000, a local fireworks depot exploded in the middle of the city of Enschede and on New Year's Eve 2001, fire destroyed a pub full of people in Volendam. Lessons from the involvement of medical services in these disasters include: disaster medicine must be seen as an extension of emergency care. Hospital staff should be familiar with the procedures in case of a disaster, and regular practice on a regular basis is mandatory. Logistics, as well as individual care of the victims, differ in detail from everyday practice, notably during the first hour following the disaster. Attention should be paid to the provision of psychological aftercare soon after the event for the victims and their families, as well as for health care workers. PMID- 11766299 TI - [Self-monitoring and self dosing of oral anticoagulant therapy with vitamin K antagonists]. AB - Anticoagulant therapy with vitamin K antagonists is effective in the prevention and treatment of thrombotic disease. The variable effect of these agents and the relatively small therapeutic width necessitate frequent checks on the intensity of the anticoagulation therapy as well as frequent dose-adjustments. Recently, small and reliable portable machines have become available which enable patients themselves, by means of a drop of blood obtained from a finger prick, to measure the intensity of the anticoagulation therapy and if necessary to adjust the treatment dose. In studies within the Netherlands where (selected) patients determined the 'international normalised ratio' (INR) themselves and if necessary adjusted the dose of the anticoagulant medication, the INR was mostly within the therapeutic target area. Furthermore, the independence, the possibility for travelling and the time saved were experienced as positive aspects. Under certain conditions, allowing patients themselves to check the INR and if needs be to adjust the dose of the anticoagulation treatment, may be an acceptable alternative for anticoagulation therapy check-ups performed by the thrombosis service. PMID- 11766300 TI - [Acute renal replacement therapy in the intensive care unit]. AB - On the intensive care department the most frequently used acute renal replacement techniques are intermittent haemodialysis and continuous haemofiltration. Although continuous techniques appear to have distinct advantages in the treatment of critically ill patients, no consistent differences in mortality have been found between continuous and intermittent treatment modalities. Due to uncertainty in this area, the use of unmodified cellulose membranes is probably best avoided. No good randomised studies are available with regard to the starting time of renal replacement techniques in critically ill patients. However, generally speaking a 'late' start should be avoided. With continuous techniques, the filtration volume should not be below 35 ml/kg/h. Although continuous (high-volume) filtration techniques may contribute to an improvement in the haemodynamics, the mechanisms behind this phenomenon remain unclear. At present, no randomised studies are available which have shown a beneficial effect of continuous techniques on the survival of critically ill patients without manifest renal insufficiency being demonstrated. PMID- 11766301 TI - [Use of trauma triage teams at the cafe fire in Volendam]. AB - For large-scale accidents, and for specific categories of wounds there is, in addition to the extramural assistance provided by helicopter teams and mobile medical teams, a need for secondary triage so that patients can be transferred as quickly as possible and the use of limited treatment capacity for specific injuries (such as serious burns) is optimised. After the cafe fire in Volendam, 203 patients were admitted to 27 hospitals. In almost all of these cases it concerned burns, often complicated by inhalation injury. Burns triage teams selected in the second instance patients with 30-80% surface burns who required artificial respiration, for admission to one of the burn centres in the Netherlands, Belgium or Aachen (Germany). The mortality under 75 patients with burns and an inhalation trauma who underwent a planned curative treatment was just 5.3%. Trauma triage teams should be officially recognised within the chain of the project 'Medical assistance in accidents and disasters' (Dutch acronym: GHOR) so that together with the uniform guidelines for the treatment of specific injuries that are present in casualty departments (for example the 'emergency management of severe burns (ESMB) protocol', a protocol for the care of patients with serious burns) the quality of care can be improved. PMID- 11766302 TI - [From gene to disease; androgen receptor gene, androgen insensitivity syndrome, and spinal and bulbar muscle atrophy]. AB - Androgen insensitivity is an X-linked disorder of male sexual differentiation resulting from a defective androgen receptor. Spinal and bulbar muscular atrophy (Kennedy's disease) is an X-linked disease, resulting from expansion of the polyglutamine stretch in the N-terminal part of the androgen receptor. Mutation analysis confirms the clinical diagnosis of androgen insensitivity and enables carrier detection and prenatal diagnosis. Kennedy's disease, with its diagnostic problem of clinical variability, is diagnosed or excluded when an expanded CAG repeat is present or absent in exon 1 of the androgen receptor. Molecular testing can be used for carrier detection and genetic counselling. PMID- 11766303 TI - [Diagnostic image (66). Pseudo-myocardial infarct due to pectus excavatum]. AB - An electrocardiographic pattern of a myocardial infarction, due to a pectus excavatum, was found in a 41-year-old woman: pseudo-myocardial infarction. PMID- 11766304 TI - [Local and regional in-hospital trauma care following fireworks depot explosion in Enschede]. AB - On Saturday 13 May, 2000 at about 15:30 h, the Dutch city of Enschede was struck by the explosion of a midtown firework depot. Twenty-two people were killed and almost 1,000 people were wounded. A complete district with 1,000 houses was destroyed. In total, 527 victims were treated in one of the regional hospitals, 76 (14%) of whom were admitted and 451 (84%) were treated as outpatients. Of the clinically treated victims, 11 patients were triaged as T1 and needed immediate intervention, 63 patients were triaged as T2 where treatment within six hours was indicated, and two T3 patients did not need urgent treatment. The outpatients mainly suffered secondary blast injuries to the head and extremities due to flying debris. Of the 11 T1 patients, 10 underwent acute surgery; intervention radiology was performed in one patient. The injuries of the severely wounded T1 patients consisted of penetrating thoracic, abdominal and skull injuries, as well as blunt abdominal trauma and compound fractures. Two patients from the disaster area underwent acute vascular surgery for acutely burst aortic aneurysms. The in hospital trauma care was characterised by the spontaneous arrival of a large number of extra medical personnel. The regional distribution of the trauma patients was adequate. The regional capacity of the emergency rooms, IC-units and operating facilities proved to be sufficient. Routing of lightly-wounded patients was found to be important. The communication in all phases of the disaster management appeared to be poorly structured. CONCLUSION: During the initial trauma care, the routing of vast numbers of ambulant, lightly-wounded patient, as well as extra doctors and nurses, needs careful planning. PMID- 11766305 TI - [Debriefing of hospital professional staff after fire in a bar in Volendam]. AB - A fire disaster in a bar on New Year's Eve 2001 in Volendam, which led to 200 victims, resulted in active participation of regional hospitals, including the academic hospital of the Free University of Amsterdam. In the first hour, more than 100 members of personnel were mobilised in this hospital. Nine doctors and nurses worked as members of medical teams at the site of the disaster; the others triaged 16 patients in the emergency room and treated 13 patients in the intensive care unit. After 4.5 hours, the influx of victims stopped and accordingly the disaster plan was deactivated. During the subsequent days, debriefings were organised on request of the hospital staff and personnel involved. These concluded that specific adjustments to hospital procedures were needed, such as a total admission stop for a few days, to prevent mental burn-out of personnel and to maintain the standard quality of care. Hospital disaster plans do not usually have specific guidelines for the emotional preparation of personnel during and immediately after a disaster, nor do they include specific guidelines for the evaluation of its emotional impact in terms of the quality of care delivered. These elements should be incorporated into every disaster plan. PMID- 11766306 TI - [Chronic hepatitis ascribed to the use of sotalol]. AB - In a 68-year-old woman with severe chronic hepatitis an extensive investigation revealed no other cause than the use of sotalol for 10 months due to atrial fibrillation. Once the use of the medication had been discontinued the patient's symptoms quickly disappeared and the liver function disorders normalised within 5 months. Sotalol is a beta-adrenergic receptor blocking and anti-arrhythmic agent. It is widely used in patients with supraventricular and ventricular arrhythmias. An adverse effect in terms of liver damage is not known. The pathogenesis of the observed hepatitis remained an enigma because sotalol is a hydrophilic substance which is not metabolized by the liver and is cleared by the kidneys unchanged. PMID- 11766307 TI - [Decision support in primary care--a vertical second opinion]. PMID- 11766308 TI - [Decision support in primary care--a vertical second opinion]. PMID- 11766309 TI - [Decision support in primary care--a vertical second opinion]. PMID- 11766310 TI - [Laryngotracheal separation procedure after oncological pharyngeal and laryngeal operations]. AB - Principles of the operative technique and indication for permanent laryngotracheal separation in chronic aspiration after oncological operations are being presented. The operation is done while the tracheostomy is present. It consists of horizontal section of the trachea on the level of the tracheostomy and formation the new one by using the lower of the trachea with the skin. Upper sublaryngeal section of the trachea is being closed by stitches. This operation was performed in our clinic in one patient after partial laryngectomy due to the cancer and in two patients after extended resection of the palatal tonsil, base of the tongue and lateral wall of the hypopharynx. In all the cases the follow up was without major complications. PMID- 11766311 TI - [Laser assisted uvulopalatoplasty (LAUP) in the treatment of snoring and obstructive sleep apnea syndrome]. AB - Laser Assisted Uvulopalatoplasty (LAUP) the surgical technique for the treatment of snoring and obstructive sleep apnea syndrome was first performed by Kamami in 1988. LAUP can reduce the airway obstruction in the oropharynx level. LAUP is the simple, reliable surgical procedure performed in an office setting under the local anesthesia, without hospitalization. From 1998 to 2000 37 patients underwent LAUP in our ENT Department in Zabrze. This group comprised of 19 OSA patients and 18 habitual snorers. In cases of nasal obstruction by turbinate hypertrophy or septal deviation we performed septoplasty or partial inferior turbinectomy by laser CO2. In some cases with palatin or lingual tonsils hypertrophy we also performed tonsillectomy or lingual tonsil laser ablation. In 5 patients LAUP was performed in several stages. Before and after the surgical treatment each patient were evaluated by PolyMESAM--the device belongs to the third diagnostic level. In all postoperative evaluated OSA patients the RDI decreased significantly. In 4 patients (50% of evaluated after LAUP patients) the RDI dropped to 10 or lower. Snoring was eliminated or significantly reduced in 83% of patients classified as the habitual snorers. No serious complications were observed. LAUP is a good alternative to UPPP in the surgical treatment of habitual snorers and some of the patients with OSA syndrome. PMID- 11766312 TI - [Objective evaluation of the influence of the tongue base reconstruction on the swallowing disorders]. AB - Laryngographic, manometric and videorentgenocinematographic examinations of swallowing were conducted on 54 patients after partial laryngectomy and on 35 subjects being a control group. Resection of a part of the base of the tongue is the factor that causes intensified difficulty during swallowing and increase in the frequency of the occurrence of aspiration. The results of manometric and videorentgenocinematographic examinations indicate that the shape and mobility of the tongue has the greatest influence on the efficient swallowing in patients who have undergone partial laryngectomy due to cancer initially located in the supraglottic area. The importance of remaining the possibly non-deformed structure and mobility of the tongue during partial laryngectomy involves the issue of reconstruction of defects occurred during the surgery. Both manometric and videorentgenocinematographic examinations confirm the effectiveness of the method involving reconstruction of defects in a part of the base of the tongue with a graft of angio-pedunculated submandibular gland. The study of effectiveness of glottis or neoglottis performed with the use of laryngograph showed no relation between glottis/neoglottis occlusion effectiveness index and intensified swallowing disorders. This shows the lack of compensating option in swallowing disorders with the help of a mechanism based on an efficient glottis or neoglottis occlusion alone. PMID- 11766314 TI - [Paranasal sinuses CT scans analysis of patients with cystic fibrosis]. AB - Thirty patients with cystic fibrosis (CF) were diagnosed of the otolaryngological outpatient clinic, a part of Department of Otorhinolaryngology Medical Academy in Warsaw, in 1996-1998. The control group was formed by thirty patients with chronic rhinosinusitis (CRS). Computed tomography (CT) scans were estimated in all cases. Results showed, that inflammatory changes are more advanced in patients with cystic fibrosis than in patients with chronic rhinosinusitis. The high progression of inflammatory changes in patients with cystic fibrosis, observed in CT scans, caused: disturbed development of a frontal and maxillary sinuses, destruction of bony structures formed the lateral wall of the nasal cavity, medical bulging of the lateral nasal wall. PMID- 11766313 TI - [Oral cavity and oropharyngeal carcinomas in the materials of the University of Medical Science, ENT Department, in Poznan, in years 1980-1999]. AB - 624 patients with malignant neoplasms of the mouth and the oropharynx treated in the ENT Department K. Marcinkowski University of Medical Sciences in Poznan between 1980 and 1999 were analysed. Since the middle of the 90-ies a rapid increase of neoplasms incidence of this location has been observed. The most numerous group were tumours of the palatine tonsil (34.8%), tongue (32.5%), floor of the mouth (5.9%), soft palate (5.3%). Advanced neoplasms which encompassed the tongue, oropharynx, mouth floor base was observed in 134 patients (21.5%). The precise definition of their site of origin primary location was not possible to establish. In the analysed group males were dominating. Heavy smoker and alcohol abuse constitute the majority of risk-factor patients. Poor dental status and mouth hygiene in this population was observed. In the histological examination squamous cell carcinoma was a dominating. Prognosis in patients with malignant neoplasms of the palatine tonsil were better in comparison with tongue cancer. PMID- 11766315 TI - [Cochlear implantation through the middle fossa approach]. AB - The inner part of cochlear implant is inserted into inner ear during surgery through mastoid and middle ear. It is a classical method, used in the majority cochlear centers in the world. This is not a suitable method in case of chronic otitis media and middle ear malformation. In these cases Colletti proposed the middle fossa approach and cochlear implant insertion omitting middle ear structures. In patient with bilateral chronic otitis media underwent a few ears operations without obtaining dry postoperative cavity. Cochlear implantation through the middle fossa approach was performed in this patient. The bone fenster was cut, temporal lobe was bent and petrosus pyramid upper surface was exposed. When the superficial petrosal greater nerve, facial nerve and arcuate eminence were localised, the cochlear was open in the basal turn and electrode were inserted. The patient achieves good results in the postoperative speech rehabilitation. It confirmed Colletti tesis that deeper electrode insertion in the cochlear implantation through the middle fossa approach enable use of low and middle frequencies, which are very important in speech understanding. PMID- 11766316 TI - [Human papillomavirus (HPV) in laryngeal leukoplakia]. AB - Epidemiological data and results of molecular studies suggest that human papillomavirus could be considered a risk factor for the upper respiratory tract cancers. HPV infection plays also the important role in the laryngeal precancerous states. Six out of 16 studied cases of laryngeal leukoplakia revealed presence of HPV DNA (37.5%). In situ hybridisation technique was used for the detection of viral DNA. PMID- 11766317 TI - [Congenital cholesteatoma in children--case reports]. AB - The authors present three cases of congenital cholesteatoma in children. In two cases primary surgery was curative, in third patient one year after first surgery the residual cholesteatoma was diagnosed, and second surgery was performed. Finally in all cases good anatomical and functional effect was obtained. The natural history of congenital cholesteatoma, as well as surgical techniques which can be applied depending on type and location of congenital cholesteatoma are discussed. The authors emphasise the importance of early recognition of the disease. Exploratory tympanotomy, or CT scan should be applied in all cases where suspected changes are observed during otoscopy. PMID- 11766318 TI - [Contribution to etiology of otitis media with effusion]. AB - BACKGROUND: Otitis media with effusion is characterized by gathering and retaining of effusion within the tympanic cavity and the structures of the mastoid bone. The aim of this study was to explain the role of immunological reaction in pathogenesis and development of this disease. MATERIAL AND METHOD: The studied group comprised 6 patients aged between 7 and 14 years. The effusion present within the tympanic cavity was aspired and then the agarare gel immunoelectrophoresis was performed. After 24 hours the precipitation stripes of the IgA and IgG were analysed. Blood serum specimens were also collected in the studied group. After centifrugation, blood serum concentrations of IgA and IgG were evaluated. RESULTS: IgA and IgG were present in the effusion taken from the tympanic cavity in all examined cases. The level of IgA was higher in older individuals. PMID- 11766319 TI - [Stuttering in old people]. AB - We can meet sometimes an opinion that the old people do not stutter. The author wanted to verify this hypothesis. 196 old people from the Veteran's Home were examined. In 4 of them a mild signs of stuttering were found, in one the signs were significant. The stutterers said that their symptoms diminished after the year of 50. PMID- 11766320 TI - [Otoacoustic emission evaluation in patients with tinnitus]. AB - Analysis of otoacoustic emission is highly objective, noninvasive and sensitive method representing cochlear function. In The Centre of ENT Rehabilitation in Poznan more than 900 patients were evaluated because of tinnitus. Standard tests were broaden by otoacoustic emission (SOAE, TEOAE, DPOAE) and results are discussed. Our results suggest that otoacoustic emission is possible to record in normally or with moderate hearing loss patients. 18 patients had SOAE. Only 2 patients had the same frequency of SOAE and tinnitus. PMID- 11766321 TI - [Latent otogenic cerebellar abscess]. AB - A case of latent otogenic cerebellar abscess is presented during chronic otitis media with cholesteatoma, in 42-year-old woman. Good results of the treatment were obtained by draining and substituting the content of abscess into antibiotic solution. PMID- 11766322 TI - [Melanoma of nasal cavity and paranasal sinus mucosa]. AB - In a group of 15 patients with malignant melanoma of the nasal cavity and paranasal sinuses the place of origin was nasal mucosa in 11 patients, the ethmoid cells in 2 cases and the maxillary sinus in 2 cases. Only 5 patients had tumour limited to infrastructure of the nasomaxillary complex, in 10 patients tumour occupied also suprastructure. Total maxillectomy was performed in 4 patients, partial maxillectomy in 8 patients with orbital exenteration in 3 patients. Of 12 patients operated on three patients died one year, two patients two years and one patient 6 years after surgery. One patient is alive 12 years, three patients are alive three years and one patient is alive one year after surgery. PMID- 11766323 TI - [A case of carcinoma adenoides cysticum in the external auditory canal]. AB - The authors present a case of a woman aged 31 with carcinoma adenoides cysticum at external auditory canal. The tumor was surgically removed; after 9 month a recrudescence was ascertained but there were no metastasis to other organs. The tumor was once more surgically removed. Now it has been a year of observation and no renewal of neoplastic process was noticed. PMID- 11766324 TI - [The personality of children with repeated nose injuries]. AB - Clinical observations of children hospitalised due to head injuries made us try to define some features of personality characteristic for this group of children. The examinations of 63 children aged 8-12 were carried out with R.B. Porter and R.B. Cattell test: What do you like doing? and What do you like to think about?. This method facilitates selection of 14 personality traits. The results proved that personalities tested in the group included the following dominating characteristics: aggressiveness, great excitability, and IQ exceeding average. PMID- 11766325 TI - [The story of one invention--the paper about rehabilitation of deafness]. AB - Author described his own patented idea, concerning magnetic induction in transfer signals to receptors of cochlea. This system made possible without touch transfer signals from microcomputer to electrodes implanted surgically to cochlea during rehabilitation of deafness by method cochlear implants. PMID- 11766326 TI - [Laryngeal mask of gastroesophageal reflux disease]. AB - Gastroesophageal reflux disease has become a serious problem not only for general practitioners but for other specialists as well. It is caused by the fact that its clinical picture and symptomatology are very rich. Beside characteristic symptoms such as: heartburn, eructation, gastric contents reflux, epigastric burning or dysphagia, there may appear extroesophageal symptoms (frequently as single or leading ones). It is generally though that the above symptoms result from the direct effect of gastric contents on throat and larynx and/or through vagus nerve. Direct effect of hydrochloric acid and other gastric juice components on larynx may be the cause of subglottic laryngostenosis, neoplastic transformation and development of squamous cell carcinoma. This, it may be concluded that gastroesophageal reflux disease should be in the sphere of interest of laryngologists as well as gastroenterologists. Cooperation of these specialists is particularly useful as it quickens the choice of proper diagnostic procedure and an introduction of an appropriate therapeutic treatment. PMID- 11766327 TI - [Surgical treatment in a case of extensive lower lip cancer]. AB - This paper reports on a patient with a advanced case of lower lip cancer, which was treated surgically. This reconstruction technique was employed with transposition of a flap of skin with muscle, which had been situated on the lower lip. The functional and cosmetic results were satisfactory. PMID- 11766328 TI - [The activity of antioxidative, lysosomal enzymes and concentration of lipid peroxidation products in comparison with standard inflammatory parameters in chronic tonsillitis before and after surgery]. PMID- 11766329 TI - [Signal transduction from receptors for hematopoietic growth factors]. PMID- 11766330 TI - [Introduction: chronic myelogenous leukemia leading advanced clinical oncology]. AB - Our understanding of the pathological molecular events underlying chronic myelogenous leukemia(CML) has rapidly grown over the past 2 decades. At the same time, new therapeutic modalities for CML which can cure or prolong survival in this formerly incurable disease, including interferon alpha administration and allogeneic hematopoietic stem cell transplantation, have been established. Now, a new molecule-specific drug, a ABL tyrosine kinase inhibitor(STI571), are developing, which is offering new hope for expanded treatment options for patients with CML. Clinical investigators and medical doctors will have responsibility in helping newly diagnosed patients with CML to properly elect treatment planning among the increased options available now. This specific number of JJ CO will be hoped to provide information to many medical oncologists beyond the hematology speciality. PMID- 11766331 TI - [Clinical manifestations and staging system]. AB - Patients with chronic myeloid leukemia(CML) are often diagnosed after a routine blood examination when a raised leukocyte count is found. The disease is biphasic or triphasic. The initial chronic phase lasts on 2-6 years without severe symptoms. But ultimately it either changes abruptly to an acute crisis phase or an accelerated phase which later progresses to the acute crisis phase. The acute phase is refractory to treatment and has a median duration of 3 months. Clinical features of the accelerated phase and the acute crisis phase are very diverse. The classification for the phases of CML proposed by the International Bone Marrow Transplantation Registry is reasonable. PMID- 11766332 TI - [Disease-related gene and tumor progression]. AB - Chronic myelogenous leukemia is a stem cell tumor characterized by the t(9; 22)(q34; 11) translocation generating the BCR/ABL chimeric gene. The BCR/ABL fusion gene shows several functions, including inhibition of adhesion to stroma cells and extracellular matrix, activation of mitogenic signalings, inhibition of apoptosis, and degradation of inhibitory proteins, and thereby causes transformation of hematopoietic progenitors. Among its functions, the signal transduction pathways activated by the fusion gene are Ras and MAP kinase pathways, Jak-Stat pathways, PI3 kinase pathways, and Myc pathways. Molecular mechanisms in blastic crisis remains largely unknown. However, loss of functions of tumor suppressor genes such as p53, RB, and p16, activation of oncogene Ras, overexpression of Evi-1 might be involved in disease progression. PMID- 11766333 TI - [Experimental systems in CML biology]. AB - It has been established that the BCR-ABL oncogene produced on the Philadelphia chromosome in human chronic myeloid leukemia(CML) directly causes leukemic transformation of multipotential progenitor cells. In order to study the molecular basis of this process, many convenient and useful biological assays have been found, including transformation of mouse bone marrow cells in primary culture and of Rat1 fibroblasts, cytokine-independent growth of dependent cell lines, retrovirus-mediated murine CML model, and transgenic mice model. New biological activities such as anti-apoptosis, anti-DNA repair, differentiation of ES cells may further give supportive explanations for clinical manifestation of CML. NOD/SCID transplantation model and conditional transgenic model may be the current best animal system by which to investigate cell dynamics in the most strict and natural circumstances. PMID- 11766334 TI - [Radiation-related CML]. AB - The clinical, cytogenetic and molecular-genetic findings of 55 patients with radiation related chronic myelocytic leukemia(CML) among the Hiroshima atomic bomb survivors were compared with 167 CML patients without a history of the radiation exposure. The retrospective analysis of the hematological data kept at the laboratory center where the survivors had been examined twice a year revealed a possible chronologic sequence in appearance of clinical and laboratory findings characteristic of CML. No particular differences were observed between the two groups in the incidence of Philadelphia chromosome and break points of the BCR gene, contrasting with those of radiation-related acute myelocytic leukemia which showed complex chromosome abnormalities without specific type of translocations, especially of 8;21 and 15;17, and a high incidence of genetic instability of the leukemic cells. PMID- 11766335 TI - [Genetic diagnosis of chronic myeloid leukemia]. AB - Chromosomal translocation t(9; 22)(q34; q11), found in 95% of patients with chronic myeloid leukemia(CML) and 30% of adult patients with acute lymphoblastic leukemia (ALL) generates a chimeric gene, BCR/ABL. There are three kinds BCR/ABL fusion transcripts of p210BCR-ABL found in CML and ALL, p190BCR-ABL mainly in ALL, and p230BCR-ABL in CML, either of which depends on the location of the breakpoints within the BCR gene. For the detection of t(9; 22) or BCR/ABL, karyotype analysis, Southern blot hybridization of the BCR gene, fluorescence in situ hybridization, and reverse transcription-polymerase chain reaction(RT-PCR) have been used. Especially, recent advance in RT-PCR methods have allowed refined quantitative detection of the BCR/ABL transcripts, which are useful for monitoring response status and detecting minimal residual disease. PMID- 11766336 TI - [Immunophenotypes on blast cells of chronic myelogenous leukemia]. AB - Immunophenotypes of chronic myelogenous leukemia(CML) in chronic phase and in blastic crisis were reviewed. CML cells in chronic phase show a relatively mature immunophenotypes, such as CD13, CD33, CD15, and MPO, but not positive for CD34, CD117, TdT, and HLA-DR. When a CML transforms into blastic crisis, the blast cells demonstrate an immature myeloid(acute myelogenous leukemia(AML)-like) phenotypes in 60-70% of cases. The blast cells which have myeloid markers show CD13, CD33, MPO. In contrast to de novo AML, these myeloid blast cells often express megakaryocytic, erythroid markers or natural killer cell markers, and in some of the cases, the myeloid blast cells have complex phenotypes, with co expression of markers from two or three lineages. The blast cells, in 25-30% of cases, demonstrate lymphoid blast phenotype characteristics similar to acute lymphoblastic leukemia(ALL), common ALL, or pre-B-ALL. In 60-80% of cases, the lymphoid blast cells co-express myeloid phenotype, fulfilling the criteria of biphenotypic leukemia. PMID- 11766337 TI - [Minimal residual disease in chronic myelogenous leukemia]. AB - The treatment of chronic myelogenous leukemia(CML) is performed mainly by interferon (IFN) or/and allogeneic stem cell transplantation. Experimentally, some patients with CML are treated by autologous transplantation. Monitoring of minimal residual disease(MRD) in each patient is most important, regardless of the treatments. To detect MRD in CML patients, bcr-abl mRNA has been quantitated by competitive or real-time reverse transcriptase-polymerase chain reaction(RT PCR) method. In patients who were treated by IFN, patients in whom the bcr abl/abl ratio at the time of maximal response were lower than 0.045% were shown to have a significantly lower release rate. Allogeneic BMT patients, in whom the bcr-abl/abl ratio between 3 and 5 months after transplantation was less than 0.02% were recently found to have a significantly lower relapse rate at 3 year. PMID- 11766338 TI - [Usefulness of a novel Blastretriever for harvesting blasts]. AB - Usefulness of a novel reagent(Blastretriever) for harvesting blasts was evaluated. Ten minutes centrifugation using this reagent yielded cell fractions rich in blast from all samples including peripheral blood(PB) and bone marrow of patients with varying hematologic malignancies(n = 40). When 10 PB samples containing less than 2% blasts were subjected to this centrifugation, on average, the harvested fractions contained 75% blasts with good viability and well preserved morphology. The harvested blasts could be investigated by flow cytometry, cytochemistry, immunocytochemistry, chromosomal analysis(G-banding and fluorescence in situ hybridization) and gene analysis(Southern blotting and polymerase chain reaction). This new reagent should provide valuable information for the management and pathophysiology of hematologic malignancies. PMID- 11766339 TI - [Differential diagnosis of chronic myeloid leukemia and the related disorders]. AB - Chronic myeloid leukemia(CML) is a generic term that includes five subtypes; i.e. chronic granulocytic leukemia(CGL) (95% of all CML, 90% are Ph+, 5% are Ph-, BCR/ABL+), atypical CML(survival is worse than that of CGL), chronic myelomonocytic leukemia(a subtype of myelodysplastic syndrome), chronic neutrophilic leukemia (Ph-, BCR/ABL-) and juvenile CML(Ph-, BCR/ABL-). It is not so easy to make a diagnosis of Ph-negative CML. Also, about 25% of adult acute lymphoid leukemia(ALL) patients and some essential thrombocythemia patients have Ph chromosome. In addition, about a half of cases with Ph-positive ALL have the same size of BCR/ABL fusion protein as that in Ph-positive CML. It is necessary to distinguish them by the distinctive morphological, cytogenetical and immunological characteristics of these diseases. PMID- 11766341 TI - [Autologous bone marrow transplantation for CML]. AB - The first line therapy for CML is IFN-alpha and/or allogeneic hematopoietic stem cell transplantation(HSCT). The indication of autologous HSCT is limited for patients with no HLA-matched donor, and is recognized as an experimental therapy. Major problems of autologous HSCT for CML are contamination of Ph1-positive cells to graft and no GVL effects. To concur these problems, many attempts have been made such as the collection of peripheral blood stem cells after high dose chemotherapy, ex vivo purging using antisense, administration cyclosporin to induce GVL effect, and post-HSCT therapy by IFN-alpha +/- Interleukin-2. Autologous HSCT for CML is still to be a hopeful candidate for pursuing cure. PMID- 11766340 TI - [Chemotherapy and radiation therapy]. AB - Stem cell transplantation and interferon-based treatment are major strategies in chronic phase CML and chemotherapy is one of limited therapeutic options when they are not available or ineffective. Hydroxyurea is superior to busulfan in better effect and lesser side effects. Homoharringtonine, a plant alkaloid, has shown cytogenetic response in one third of patients who were resistant to interferon therapy, and a better response rate in combination with cytarabine and interferon alfa. There have been no improvement of clinical outcome in treatment of accelerated phase and blastic crisis although many trials including decitabine are going on. PMID- 11766342 TI - [Allogeneic stem cell transplantation]. AB - Over the last two decades, four major therapeutic approaches have dramatically changed the prognosis in chronic myelogenous leukemia(CML). Those include allogeneic stem cell transplantation, interferon-alpha based regimen, donor leukocyte infusions, and the revolutionary BCR/ABL tyrosine kinase inhibitor such as STI571. Each modality has exploited and targeted different aspects of CML biology, and is associated with different risk-benefit ratios. In this section, we update the results of both related and unrelated donor transplantation, donor lymphocyte infusions, and non-myeloablative stem cell transplantation in CML in comparison with the other treatment modalities. PMID- 11766344 TI - [Treatment of chronic myelogenous leukemia with tyrosine kinase inhibitor]. AB - STI571(imatinib) selectively inhibits the ABL-tyrosine kinase, the activity of which is activated by the formation of chimeric BCR/ABL. Phase I study in USA showed a remarkable effectiveness of STI571 in interferon-refractory chronic myelogenous leukemia with little adverse effects. STI571 will plausibly become the first choice drug prior to stem cell transplantation and interferon in the treatment of this leukemia. PMID- 11766343 TI - [Interferon-alpha therapy]. AB - Interferon-alpha (IFN alpha) with or without Ara-C is a choice of therapy for patients with CML who cannot receive allogeneic stem cell transplantation and gives those better prognosis than a conventional chemotherapy, although it has a variety of adverse effects. Especially, in a certain population(about 20%) of CML patients, IFN alpha can induce complete cytogenetic response in spite of persistant minimal residual disease. The basis of IFN alpha activity against CML is still unknown, but the contribution of immune-mediated mechanism is expected. PMID- 11766345 TI - [Treatment plan and informed consent]. AB - Since STI571, a BCR-ABL tyrosine kinase inhibitor, has made a great therapeutic advance in the management of CML, we have to reconsider the treatment protocol for chronic phase CML. Interferon-alpha (IFN-alpha) will be replaced with STI571 therapy. However, some patients are reported to become refractory to STI571, and it is unclear whether STI571 therapy alone may be sufficient to induce long-term survival in CML. There are also important progress in the field of allogeneic hematopoietic stem cell transplantation (SCT); i.e. minitransplant(non myeloablative SCT) and cord blood stem cell transplantation. Currently, newly diagnosed CML patients in chronic phase should be initially treated with STI571. If the patients are appropriate candidates for allogeneic SCT and have HLA indentical sibling donors, allogeneic SCT should be conducted within one year. The other patients should also receive related or unrelated allogeneic SCT if Ph suppression is insufficient with STI571 therapy for several months. The patients who are not candidates for allogeneic SCT may be treated with IFN-alpha and/or Hydrea(or cytosine arabinoside) in addition to STI571 if they become refractory to STI571. Since each therapeutic modality has different risk and benefits, informed consent is very important to determine the treatment plan for individual patients. PMID- 11766346 TI - [Diagnosis and treatment of juvenile myelomonocytic leukemia(JMML)]. AB - Juvenile myelomonocytic leukemia(JMML) is a rare myeloproliferative disorder of early childhood. It is usually characterized by peripheral monocytosis, increased level of HbF, and hypersensitivity of hematopoietic progenitors to granulocyte macrophage colony-stimulating factor and hepatosplenomegaly. The pathogenesis of JMML has been associated with deregulated signal transduction and growth factor hypersensitivity. Allogeneic stem cell transplantation is the only curative approach but the roles of pretransplant chemotherapy, conditioning regimen and graft-versus-host disease are still unclear. Graft-versus-leukemia effect may play an essential role because withdrawal of immunosuppressive therapy and donor lymphocyte infusion was successful in the relapsed patients after transplantation. PMID- 11766347 TI - [Therapeutic application for the aged with CML]. AB - Therapeutic application for elderly CML patients had been restricted to use of alkylating or antimetabolite agents. In order to improve quality of life in the aged with CML interferon-alpha therapy is now first choice for treatment of elderly chronic phase of CML patients under appropriate informed consent. This treatment provided long term survival with cytological and cytogenetic responses even in the aged. In elderly patients attention has to be paid for the occurrence of side effects such as psychological changes. Further studies are on going in special reference to molecularly targeted therapy, i.e. a specific inhibitor of tyrosine kinase, or non-myeloablative stem cell transplantation. PMID- 11766348 TI - [Management of complications in patients with chronic myelogenous leukemia]. AB - Management of complications in patients with chronic myelogenous leukemia(CML) were reviewed. In chronic phase, the complications due to the increased WBC are not common. Currently, most patients are treated with interferon and/or hydroxyurea. Although the clinical benefit of interferon therapy has been proven with randomized trials, side effects with interferon are significantly higher than hydroxyurea. Common side effects are fatigue, weight loss, insomnia, depression and neurotoxicity. The complications following stem cell transplantation are classified into three categories: 1) regimen related toxicities of heart, lung and liver, 2) acute complications related to hematoimmune disturbance including acute and chronic graft-versus-host disease and infectious complications, 3) long term consequences of stem cell transplantation. During blastic phase, management of infectious complications is important. PMID- 11766349 TI - [Clinical epidemiology]. AB - Although the exact incidence of chronic myeloid leukemia(CML) in Japan is obscure, the occurrence rate of CML is approximately 15% of all leukemia patients in Japan, and thus about 5/100,000 cases appeared per year. This incidence of CML seems to be lower that that of Caucasian, but the incidence of CML patients in Japan may increase gradually. Molecular investigation in CML disclosed the exact mechanism of t(9; 22) anomaly, thus providing appropriate classification for chronic myeloid leukemia. From the etiological aspect, it is well documented that exposure to atomic bomb at Nagasaki and Hiroshima actually induced CML, however, factors other than irradiation are still obscure. Recent spread of annual examination pick up some CML patients at the early phase and the disease severity might be thus different from those of previous CML patients. For example, currently diagnosed CML patients usually lack palpable splenomegaly and some of them had normal karyotypes in addition to Ph-cells in the bone marrow at the time of CML diagnosis. These findings indicate that epidemiological aspect in CML patients might be changing. PMID- 11766350 TI - [Dendritic cell therapy]. AB - Dendritic cells(DC) are most powerful antigen presenting cells for the induction of antigen specific T cell response. They have been successfully used in clinical pilot study to induce tumor specific immunity as well as clinical response in selected patients. Here we report the ability of DC therapy against chronic myelogenous leukemia(CML). Three patients with CML received a series of four infusions of CML-specific bcr/abl peptide-pulsed autologous DCs. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of patients. DC vaccination induced delayed-type hypersensitivity(DTH) reactivity toward KLH in all patients, as well as positive DTH reaction to peptide-pulsed DC in one patient. Clinical responses have been measured with no patients. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of CML patients. PMID- 11766351 TI - [Non-myeloablative/reduced-intensity hematopoietic stem cell transplantation for chronic myelogenous leukemia]. AB - Allogeneic hematopoietic stem cell transplantation(HSCT) is a curative therapy against a variety of hematological disorders. However, its application has been limited to younger patients without organ dysfunctions due to transplant-related toxicities. Recently, non-myeloablative stem cell transplantation(NST) or reduced intensity stem cell transplantation(RIST) has been developed as a less toxic HSCT, which enables the application of HSCT to patients of advanced age or with organ dysfunction. The anti-leukemia effect mainly depends on the graft-versus leukemia(GVL) effect. Chronic myelogenous leukemia(CML) has been known to be one of the best targets for GVL effect, supported by the observation of durable molecular remission after donor lymphocyte infusion for relapse after HSCT. RIST could be a promising treatment modality for patients with CML. PMID- 11766352 TI - [Umbilical cord blood transplantation]. AB - Umbilical cord blood transplantation(CBT) from HLA-mismatched unrelated donors has been increasingly performed. One of the advantages of unrelated CBT is a low risk of severe acute graft-versus-host disease(aGVHD). The degree of HLA disparities is not strongly associated with the occurrence of severe aGVHD. The disadvantages of CBT include a delayed time of hematopoietic recovery and a high rate of graft failure, which are significantly associated with the lower number of infused cord blood cells. Despite a relatively high rate of early transplant related mortality, cord blood cells from HLA-mismatched unrelated donors should be considered as an alternative hematopoietic stem source for both children and adults who have no suitable related and unrelated bone marrow donors. Further clinical and laboratory studies are needed to improve the outcome of CBT. PMID- 11766353 TI - [Target therapy for CML--applying maxizyme]. AB - Hammerhead type ribozyme, which have been frequently used for the purpose of specifically cleaving RNA at the GUC triplets in the experimental setting, can not be generally applicable for the gene therapy of leukemia with gene translocation. This is because the translocated sequence does not necessarily have the GUC triplets at the site of translocation. The introduction of new strategy which can specifically digest the chimera gene is considered to open new leukemia therapy with gene translocation. Maxizyme, a newly developed heterodimeric shortened ribozymes, can theoretically digest any types of chimeric genes at the site of translocation. In this review, our interesting results suggested the possible application of this maxizyme system for the treatment of chronic myelogenous leukemia with bcr/abl gene translocation. PMID- 11766354 TI - [Genomic medicine]. AB - The International Human Genome Sequencing Consortium announced they have got a draft sequence of the human genome that covers about 94% of the human genome in February, 2001. This statement implies that we will soon have the complete human genome sequence and that we will be able to use genomic information in every field including medicine, drug production as well as prophylaxis of many diseases. Two major advances in technology have made it possible to apply genomic information for medicine: microarray technology and high-throughput sequencing technology. Microarray provides us a new method to classify various diseases on the basis of gene expression and high-throughput sequencing enables us to draw high-resolution SNPs map. PMID- 11766355 TI - [Molecular mechanisms of endothelial dysfunction in diabetes mellitus]. AB - Diabetes is a strong risk factor for vascular diseases. Recent studies have shown that disruption of endothelial cell function results in vascular injury. One of causes underlying the endothelial dysfunction in diabetics is hyperglycemia. Many epidemiological studies demonstrated that hyperglycemia increased the incidence of macrovascular diseases. In contrast to the microvascular complications in diabetes, however, the macrovascular complication often develops even in patients with good glycemic control, suggesting that some factors other than hyperglycemia may contribute to it. Insulin resistance is one of possible candidates for that. In fact, it is shown that insulin resistance is an independent risk factor for atherosclerosis. In this article, we reviewed recent hypothesis explaining how hyperglycemia or insulin resistant state caused endothelial dysfunction. PMID- 11766356 TI - [HGF as a key molecule in cardiovascular diseases]. AB - Hepatocyte growth factor(HGF) is focused as a powerful endothelial growth factor in the field of cardiovascular diseases. As its physiological role in atherosclerosis, restenosis, angiogenesis etc is very important, HGF-based new treatments for various diseases are expected. Clinical gene therapy for restenosis and ischemic diseases using VEGF gene have already performed in USA, and they could show beneficial effects of such strategies. In Japan, gene therapy using HGF gene for ASO has just begun in spring 2001. In near future, powerful therapeutic effects of HGF could applied to restenosis, graft failure, cardiomyopathy, cerebral vascular diseases, renal failure and so on. PMID- 11766357 TI - [Novel actions of HMG-CoA reductase inhibitors(statins)--vascular and cerebral protection through inhibition of small GTPase Rho]. AB - Clinical trials have demonstrated the beneficial effect of HMG-CoA reductase inhibitors(statins) for stroke prevention, independent of their lipid-lowering effects. Recent experimental progress indicated the effects of statins for brain protection on both vascular walls(endothelium, smooth muscle, inflammatory cells and platelets) and extra-vascular tissues(brain parenchyma). These pleiotropic effects of statins have been, at least in part, ascribed to inhibition of small GTPases Rho and Ras, which require isoprenoids (intermediates of the cholesterol biosynthesis pathway) for activation. Importantly, statin inhibition of Rho (1) attenuates the infarct size in a rat model of brain ischemia via the elevation of eNOS expression, and (2) suppresses vascular smooth muscle proliferation through up-regulation of CDK inhibitor p27kip1. The novel action of statin, as inhibitor of small GTPase family, should expand its potential toward integrative organ protection, beyond its conventional lipid-lowering and anti-atherogenic effects. PMID- 11766359 TI - [Results of two-step tuberculin skin test against medical and nursing school students and treatment according to the results of the test]. AB - To assess the risk of tuberculosis infection in medical and nursing school students, tuberculin skin tests were carried out in the two-step manner. The second tuberculin skin test was repeated two weeks later excluding those who were strongly positive in the first test. BCG vaccination was done with the consent of students who showed negative reaction twice. Medical interview and revaluation of prior routine chest radiogram were made on students who were strongly positive. Prophylactic INH medication was considered to those who are at high risk of tuberculosis. Eight hundred thirty eight students underwent the two-step tuberculin skin test, and among them, 771 students showed the positive reaction on the first test (92.0%) which included 58 weakly positive (6.9%), 347 intermediately positive (41.4%) and 366 strongly positive (43.7%) and 2 not measurable (0.2%), and 65 students were negative (7.8%). The average size of the erythema was 30.9 +/- 18.8 mm on the first test and 37.9 +/- 20.6 mm on the second test. Twenty one students were negative on the second tuberculin skin test, and among them, 15 received BCG vaccination. Out of eight students who were vaccinated with BCG in 1999 and were followed up in the next year, 6 (75.0%) converted to positive. Strongly positive reaction was seen in 28 students (3.3%) and one of them underwent prophylactic medication of INH according to her family history of exposure to tuberculosis. PMID- 11766358 TI - [HIV seroprevalence in patients with tuberculosis]. AB - The number of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) in our hospital is increasing year after year. Although most patients were HIV tested because of miliary tuberculosis or extra-pulmonary tuberculosis, some patients were found HIV seropositive by chance. In order to determine the incidence of HIV seropositivity among TB patients, HIV testing was carried out in TB patients for two years from January 1998 with the consent of patients. TB patients who received anti-HIV antibody examination were 164 in 1998, and 149 in 1999 and among them HIV seropositive TB patients were 4 in 1998 and 6 in 1999. The incidence of HIV seropositivity was 3.2% in all TB patients, 28.6% in miliary TB patients, and 1.0% in typical TB patients. The number of patients co-infected with HIV and TB in Tokyo was estimated by using these HIV seropositivity, it was 23 cases/year among miliary TB patients and 16 cases/year among typical TB patients. As there were many HIV-infected persons and many TB patients in Tokyo, it was thought that HIV testing in TB patients was important for the early detection of HIV infection and the early initiation of HIV treatment. PMID- 11766360 TI - [The intervention against an outbreak of pulmonary tuberculosis in the dormitory of construction laborers--Connection with approaches from public health, medical treatment, social welfare, and labor management]. AB - An outbreak of pulmonary tuberculosis (TB) in a dormitory of construction laborers took place, and this outbreak was presumed to be caused by the same sourse of infection, based on the results of restriction fragment length polymorphism (RFLP) analysis and other findings. After the first patient was admitted to the hospital with active TB, 18 new other TB patients were discovered by repeated contacts examinations. They were all male and single, and were aged from 41 to 67 years old (mean age 51.7). Among 19 patients, only 4 patients had a health insurance. As these patients lived together in the same dormitory, to prevent infection through close contact in the dormitory, repeated contacts examinations were further performed. In addition, several medical, social, and economical interventions were needed for these patients. It was also required to improve labor conditions in this construction company. It was concluded that comprehensive approaches including public health, medical treatment, social welfare, and labor management aspects were indispensable to prevent TB among relatively poor laborers. PMID- 11766361 TI - [Anti-tuberculosis drug resistance in Japan and in the world]. AB - In 1994, the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD) launched a global project on anti tuberculosis drug resistance surveillance. The results from the first 4 years (1994-1997) and the second 4 years (1996-1999) of the projects were reported in 1998 and 2000, respectively. These surveillance results showed that resistance to anti-tuberculosis drugs is a global problem. The reports also showed that there were several hot spots around the world where prevalence of multidrug resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampin) was particularly high and could possibly threaten control programs. The Tuberculosis Research Committee of Japan (Ryoken) has conducted nationwide surveys for drug resistant tuberculosis at 2- or 5-yearly intervals since 1957. The 1997 survey showed that among patients with no prior treatment, resistance to any of the four drugs was found in 10.3%, and the prevalence of primary MDR was 0.8%. The prevalence of drug resistance in the previously treated cases was 42.4% for any of the four drugs and 19.7% for MDR, indicating a high prevalence rate compared with those reported in the global project. Compared with the previous survey in 1992, the current survey shows increased prevalence of drug resistance in both new and re-treatment cases. No significant differences in resistance rates by sex, age group, nationality, district, and/or accompanying diseases were observed in any of the new or re-treatment cases. Other factors associated with the high prevalence in re-treatment cases remain to be determined. A total of 78 hospitals in various districts of Japan participated the cooperative study. Each collaborating laboratory sent all the isolated mycobacterial cultures to the Research Institute of Tuberculosis (RIT). In the local laboratories, the absolute concentration method using 1% Ogawa egg slant, its modified methods using a 48 well plate and a 16-well plate, combination of above 2 or 3 methods, and other method were used for drugsusceptibility testing, and the proportion method using 1% Ogawa egg slant was used in the RIT. The results in the local laboratories were compared with those in the RIT. There was no significant difference in the concordance rates according to the test drugs among methods for drug susceptibility testing used in the local laboratories. Relatively lower concordance rates were seen in the laboratories using the Microtiter method related to high overestimation rates, compared with those in the laboratories using the standard method and Well-pack method. However, relatively lower concordance rates (less than 90%) were seen in the laboratories using any of the three methods, indicating that there are variations among facilities. PMID- 11766362 TI - [Medical treatment support to tuberculous patients--from the standpoint of community support]. AB - A symposium with "Medical Treatment Support to Tuberculous Patients--From the standpoint of community support" as its theme was held at the 76th Annual Meeting of the Japanese Society for Tuberculosis (April 20, 2001). "Once, It is infected with tuberculosis, one have to complete medication with a sensitive antituberculosis drug by observing the prescribed dose and duration for successful treatment". For this to be promoted community, it is necessary that (1) to manage patient's medication by medical facilities, (2) to support patient's medication by health center and (3) to support patient's living by welfare offices. Not that each facilities takes such responsibilities alone, but various community must fulfill them continuously in liaison with one another. On what measures should be taken to that end, reports based on practical examples from Nagoya City, Yokohama City and Kanagawa Prefecture have been compiled as follows. 1. It was in-office liaison by conference that supported the DOTS activities of health nurses. 2. It is cooperating, without health, medical treatment, and welfare going out, as follows. (1) A system for hospitals and clinics to carry out DOTS treatment consistently has been kept in good condition. (2) For a patient to take a drug in front of a nurse has become common, causing the patients to be motivated. (3) Assignment of MSW and nurses in charge of DOTS sent from hospitals has make it possible to offer or exchange information smoothly among those concerned. (4) A system for many persons concerned to support patients timely has been kept in good condition. This resulted in an increase in the cure rate of tuberculosis in the areas which have day laborers' lodgings. 3. By DOTS for in-patients, the number of self-discharges has decreased by 1/3, and the treatment completion rate was 94%. 4. In promotion of DOTS for the patients who have health problems other than tuberculosis, the role MSW plays is great. 5. As conditions for supporting DOTS promotion, it is necessary to create a system by which to stabilize the living of the patient himself, guarantee earnings to support it and dissolve the living problem faced by the patient. 6. Introduction of the "early guidance system for the patients in whom the treatment of tuberculosis" was discontinued has strengthened the liaison between health offices and medical facilities, has led to early detection in persons yet to receive medical treatment and resumption of medical treatment, making it possible to deal with problem cases effectively on a priority basis. It has been confirmed that liaison between health, medical service and welfare for community support of the treatment of tuberculous patients who live in that community resulted in improvement of clinical results of tuberculous patients. In this connection, Dr. Shirai advised "For a tuberculous patient to form a habit of taking a drug wherever he lives needs to be recognized as a major subject". He presented the forcible yell. "Any local government office has the homeless. I want you to make efforts so that DOTS be given to all the tuberculous persons. If there is any problem, I am ready to give advice." PMID- 11766363 TI - [Laparoscopic radical prostatectomy: initial 17 case report]. AB - PURPOSE: We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer. MATERIAL AND METHOD: Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1 ng/ml, 6, respectively. We followed the operation technique from the "Montsouris technique". Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures. RESULTS: No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600 ml (range 100 to 3,135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2 ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent. CONCLUSION: Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer. PMID- 11766364 TI - [Immunohistochemical study of p53 and Ki-67 overexpression in grade 3 superficial bladder tumor in relationship to tumor recurrence and prognosis]. AB - PURPOSE: The major drawback of the current treatment for superficial bladder tumor is the high rate of recurrence. Especially, the tumor with grade 3 component has a tendency to recur and progress in stage. However, we have difficulty in predicting tumor recurrence and stage progression accurately by conventional clinicopathological factors. We evaluated the efficacy of p53 and Ki 67 overexpression as a predictor of recurrence or prognosis in patients with superficial bladder tumor of grade 3. MATERIALS AND METHODS: Samples were obtained from 41 patients with superficial transitional cell carcinoma of the bladder of grade 3 who were treated by transurethral resection (TUR). The immunohistochemical study was performed using the antibodies against the p53 protein and Ki-67 antigen on formalin-fixed, paraffinembedded tissue specimens from initial tumors. We evaluated the correlation between these results and several clinicopathological factors. RESULTS: The p53 index and the Ki-67 index in pTa, pT1a and pT1b tumors were 26.4 +/- 30.1%, 28.6 +/- 30.0%, and 34.6 +/- 32.6% (p53) and 20.5 +/- 22.5%, 20.0 +/- 29.3%, and 29.2 +/- 28.4% (Ki-67). There was no significant difference between the each index and tumor stage. Eighteen cases (43.9%) had intravesical recurrence. The p53 index of the initial tumor from the tumor free cases (n = 23), recurrent cases without stage progression (n = 12), and stage progression cases (n = 6) were 19.7 +/- 28.2%, 42.0 +/- 28.7%, and 42.5 +/- 32.0%. Between the recurrence-free cases and the recurrent cases without progression, the p53 index of the initial tumor had statistical significance (p < 0.05). The Ki-67 index was shown to be the same pattern as the p53 index, but there was not statistical significance. Four of patients with stage progression had tumor progression within six months. Three of the patients with tumors with stage progression died of the cancer. In multivariate analysis, tumor multiplicity (p = 0.01), BCG intravesical instillation (p = 0.04), p53 index (p = 0.01) and Ki-67 index (p = 0.02) were the positive risk factors for tumor recurrence, but only the p53 index was the positive risk factor for prognosis fo the patients (p = 0.03). CONCLUSION: These results suggest that the immunohistochemical study of p53 overexpression is a useful predictor for tumor recurrence and prognosis in patients with superficial bladder tumor with grade 3. PMID- 11766365 TI - [Influence of erectile dysfunction on daily life and general attitudes towards treatments]. AB - OBJECTIVES: This study investigates the influence of erectile dysfunction (ED) on daily life and the attitude of citizens toward ED treatments. MATERIALS AND METHODS: A mail survey targeting married males and females, aged 30-79, was conducted throughout the nation. The effective responses were 2,034 males and 1,820 females. RESULTS: The ED prevalence rate of male respondents was 29.9% and that of females (indicating the recognition of husband's ED) was 30.1%. For both males and females, the frequency of sexual intercourse and satisfaction about their sexual lives were significantly lower in respondents with ED. 23.6% of males with ED and 16.0% of females whose husbands have ED experienced a negative influence of their married lives. Among male ED sufferers, however, only 4.8% of them had consulted a physician. The reasons cited most often for not consulting a physician were: "no influence on daily life", "not annoyed by ED", and "no interest in sex", Moreover, the barriers to visiting physicians were frequently cited, such as "shyness", "don't know which hospital to go to", and "expensive". With regard to insurance coverage of ED treatment, 80% or more of both men and women say that "it should be reimbursed for all ED patients" or "it should be conditionally reimbursed". CONCLUSIONS: It becomes clear that ED is found at considerable frequency. However, only 4.8% of ED patients had received appropriate treatment at medical facilities. With regard to insurance coverage for ED treatment, it turned out that 80% or more of both men and women supported reimbursement for ED treatment. PMID- 11766366 TI - [Comparison of digital subtraction angiography, CT angiography, and ultrasonic Doppler examination in the evaluation of penile arterial lesions]. AB - BACKGROUND: CT angiography reconstructed by a multidetector-row helical CT scanner is a newly developed form of imaging. We compared CT angiography and ultrasonic Doppler examination with digital subtraction angiography (DSA) in the diagnosis of arterial lesion. METHOD: Eighteen patients with arteriogenic erectile dysfunction (ED) underwent color Doppler study, DSA, and CT angiography after providing informed consent. The CT angiography images were obtained by a multidetector-row helical CT scanner, Asteion TSX021A (TOSHIBA). We injected prostaglandin E1 into the penile cavernous body, and then rapidly infused nonionic contrast medium into the antecubital vein. DSA and CT angiography images of the bilateral internal pudendal arteries and cavernous arteries were examined for stenotic lesions or occlusion. We also compared the peak systolic blood flow velocity in the cavernous artery measured by color Doppler ultrasound with CT angiography and DSA. RESULTS: The CT angiography and color Doppler studies were performed on an outpatient basis, but DSA required hospitalization. In the 36 internal pudendal arteries, DSA represented 22 normal arteries and 14 stenosis or occlusions. CT angiography showed 15 normal arteries and 21 occlusions. For the diagnosis of stenosis or occlusion in the internal pudendal artery, the CT angiography image had a good agreement, with a sensitivity of 1.00, specificity of 0.68, and accuracy of 0.81. For diagnosis in the cavernous artery, CT angiography image also showed a good agreement with DSA; however, the quality of the images of fine arteries was better in the DSA images. The inferior view and internal view of the pelvis in CT angiography were helpful for visualizing the internal pudendal artery, especially at the pubic bone. There was insufficient correlation between peak systolic blood flow velocity and DSA findings. There were no serious complications involved in either examination. CONCLUSIONS: CT angiography has not yet reached the same level as DSA in the evaluation of fine arteries. However, CT angiography can produced images sufficient for the diagnosis of arteriogenic ED with some advantages. We believe that with improvement, CT angiography will become an adequate replacement for DSA in the diagnosis of penile arterisl lesion. PMID- 11766367 TI - [Clinical efficacy of leuprolide acetate and combined treatment with estramustine for advanced prostate cancer]. AB - BACKGROUND/PURPOSE: Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS: One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS: Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION: Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug. PMID- 11766368 TI - [Renal cell carcinoma metastatic to the ovary: a case report]. AB - A 47-year-old woman underwent left radical nephrectomy in 1995, and pathological diagnosis showed a primary renal cell carcinoma with clear cell subtype. Four years later on her routine checkup, abdominal computerized tomography revealed a 9-cm of predominantly solid and partially cystic tumor in the pelvic cavity. The patient was referred to Gynecologic Department and a total hysterectomy with bilateral salpingo-oophorectomy was subsequently performed under the diagnosis of a left ovarian tumor. A cut surface of the solid component of the tumor was macroscopically yellowish. Pathological examination revealed alveolar growth of tumor cells with abundant clear cytoplasm including fat components. In some areas of the tumor, there were patterns of tubular structures which were cystically dilated. The typical findings usually found in the primary ovarian clear cell adenocarcinoma were absent in the tumor, and the final pathological diagnosis was left ovarian metastasis of renal cell carcinoma. The ovarian metastasis of renal cell carcinoma is quite rare and to our knowledge only eleven cases were reported in the past 20 years. We report on a case and review the literature. PMID- 11766369 TI - [A male case of primary bilateral breast cancers during estrogen therapy for prostate cancer]. AB - An 82-year old man received total androgen blockade therapy (bilateral orchiectomy and 375 mg/day flutamide) for the treatment of stage C prostate cancer. Serum PSA levels were undetectable for 13 months and thereafter increased gradually. We administered estramustine phosphate sodium (EPS) instead of flutamide under the diagnosis of hormone refractory prostate cancer. EPS therapy was discontinued after 9 months because serum PSA levels increased again. Then, the patient complained of bilateral breast nodules and pain. Bilateral mammectomies were performed due to bilateral breast cancers which had been diagnosed by aspiration biopsies and radiographic examinations, but he died four months after the operations. Final pathological diagnosis was ductal adenocarcinoma of the breasts. Immunohistochemical study revealed expressions of PSA in the breast cancers. We diagnosed double cancers of the prostate and the breast because of the different expression patterns of progesterone receptor between them. We review the literatures and discuss the differential diagnosis of prostate cancer and PSA-producing breast cancer. PMID- 11766370 TI - [A case of heparin-induced thrombocytopenia after transurethral resection of prostate during anticoagulant therapy]. AB - A 66-year-old man had been receiving anticoagulant therapy for myocardial infarction with warfarin potassium (abbreviated as warfarin) 2 mg/day. Though he had been treated with tamsulosin hydrochloride 0.2 mg/day as diagnosis of benign prostatic hyperplasia, he experienced severe dysuria and wanted to undergo transurethral resection of the prostate. We decided to continue anticoagulant therapy because cardiologist judged that intermission of anticoagulant therapy could cause myocardial infarction. Warfarin 2 mg/day p.o. was replaced with heparin sodium (abbreviated as heparin) 5000 u x 2/day s.c. 6 days prior to surgery, and anticoagulant therapy was stopped on the day of surgery, but resumed on the following day. Purpura appeared around the extremities 18 days after the surgery. Although coagulation testing was normal, platelet counts had markedly been reduced (2,000/mm3). Platelet counts recovered to a level of 228,000/mm3 13 days after cessation of heparin. No other adverse effects were observed. Heparin induced thrombocytopenia (abbreviated as HIT) was diagnosed clinically. We consider monitoring of platelets to be necessary because an increasing number of patients are on anticoagulant therapy in Japan, and accordingly, the use of heparin is likely to be increased. PMID- 11766371 TI - [A case of septic shock and disseminated intravascular coagulation following transrectal prostatic biopsy]. AB - A 60-year-old man underwent transrectal six sextant ultrasound-guided prostatic biopsy because of gradual elevation of PSA. Despite postoperative use of amikacin, spiking fever developed the next day and after emergency admission (39 hours after the biopsy), his blood pressure decreased to 56/40 mmHg with WBC 800/mm3, platelets 6.9 x 10(4)/mm3 (decreased further to 0.4 x 10(4)/mm3 on the following day) and FDP 51 micrograms/dl. Intensive care including chemotherapy with broad-spectrum antibiotics and endotoxin removal therapy using a polymyxin B immobilized fiber column (PMX), was useful to recover the patient from septic shock and disseminated intravascular coagulation. As the number of systematic prostatic biopsy is increasing rapidly in Japan, more attention must be paid to potential hazards of this procedure. PMID- 11766372 TI - [Two cases of renal cell carcinoma that underwent radical nephrectomy subsequent to complete tumor enucleation]. AB - We have reported the favorable therapeutic results of non-ischemic complete enucleation using a microwave tissue coagulator as a method of nephron-sparing surgery for small renal cell carcinoma (RCC). We experienced two elective cases that underwent translumbar nephrectomy subsequent to the tumor enucleation. The first case showed another RCC in a cyst, concomitant with the enucleated RCC. The second case was a pT3a spindle cell carcinoma with high-grade malignancy. We decided to nephrectomize these enucleated kidney after obtaining well-informed consent. Here we report these controversial cases and discuss about the indication and outcomes of complete tumor enucleation for small RCC. PMID- 11766373 TI - [Genetic diagnosis and molecular epidemiological analyses of hand, foot and mouth disease which prevailed in Osaka Prefecture in 2000]. AB - Direct rapid genetic diagnosis by RT-PCR as well as virus isolation was performed on the 122 patients with hand, foot and mouth disease (HFMD) in Osaka Prefecture in 2000, followed by molecular epidemiological analyses of the isolated viruses. MRC-5 cells showed the highest sensitivity for virus isolation, recovering 59 strains of viruses from 80 virus-positive patients. By RT-PCR using newly designed primers spanning VP4 and VP2, corresponding genome regions of coxsackievirus type A16 (CA16) and enterovirus 71 (EV71) isolates were amplified only with primers specific to respective viruses. On the other hand, none of the genomes of prototype enteroviruses of other 49 serotypes were detected with these primers. From the sequence analyses, all of the 22 isolates of CA16 belonged to the same genotype and 33 isolates of EV71 were classified into two genetic groups. The results showed that 3 different genotypes of viruses were prevailing in the epidemic of HFMD in Osaka Prefecture in 2000. PMID- 11766374 TI - [A pertussis outbreak in a ward for severely retarded]. AB - In June 2000, many cases with persistent cough were observed among inpatients and the staff of a ward for severely retarded. Some of them had symptoms suggestive of pertussis, such as whooping, post-tussive apnea. We performed a retrospective investigation to assess symptoms and serological findings suspicious of pertussis. There were a total of 14 cases of persistent cough over 3 weeks (4 to 9 weeks). 6 cases were inpatients and 8 were hospital staff. Of those, serological test for pertussis infection was performed in 10 cases and 6 cases were diagnosed as serologically confirmed pertussis. The other cases with persistent cough were also considered to be probable pertussis as they have had intensive contact with serologically confirmed cases. 12 cases were treated by antibiotics, but they all failed to respond. It was suggested that Bordetella pertussis must be considered as a causal organism of persistent cough even in adults. To prevent nosocomial transmission of pertussis, droplet precautions and macrolide treatment should be provided for patients with symptoms highly suggestive of pertussis. PMID- 11766375 TI - [Increasing incidence and the mechanism of resistance of nalidixic acid resistant Shigella sonnei]. AB - One hundred and fourteen Shigella sonnei strains obtained in 1991 to 2000 were tested for their susceptibilities to 12 antimicrobial agents. Nalidixic acid (NA) resistance was found in 2 of 15 strains (13.3%) in 1993, 2 of 8 strains (25%) in 1996, one of 5 strains (20%) in 1998, 7 of 21 strains (33.3%) in 1999 and 6 of 12 strains (50%) in 2000. The incidence of resistance to NA in S. sonnei strains increased significantly during this period. Among those 19 NA resistant strains, 11 strains were derived from patients with traveler's diarrhea and 8 strains were derived from patients who had not traveled abroad before the infection, namely domestic patients. PFGE analysis with Xba I revealed that all strains tested differentiated into two major clonal clusters, one cluster consisted of strains derived from patients who had traveled to India after 1993, and another cluster included strains derived from domestic patients. Mechanism of NA resistance was examined by sequencing the quinolone resistance-determining region (QRDR) of gyrA gene. Among 19 NA resistant strains tested, 11 strains presented a change at Ser 83 to Leu and 7 strains presented a change at Asp-87 to Try (5 strains) or Asn (2 strains), whereas 3 NA sensitive strains had no change in the region. These findings indicated that this mutation in gyrA plays an important role in acquisition of Nalidixic-acid resistance in clinical isolates of S. sonnei. PMID- 11766376 TI - [Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization among patients with neoplastic disease: a clinico-epidemiological study of 11 cases]. AB - MRSA infection or colonization developed in eleven patients with neoplastic disease including malignant lymphoma (5 cases), soft tissue sarcoma (2 cases), acute myeloblastic leukemia (one), myelodysplastic syndrome (one), multiple myeloma (one), and mesothelioma (one) at our ward from October to December 1999. The infections were pneumonia (six cases), enteritis (three), bacteremia (one), and wound infection (one). Ten of 11 cases received antimicrobial agent (s) during one month before isolation of MRSA, suggesting selection of MRSA. Five cases improved and survived, but six cases died of infection. At the isolation of MRSA, the neutrophil count (NC) of the alive cases was 1, 500/microliter or more but the NC of five cases who died was less than 1,000/microliter, especially less than 100/microliter in three cases who had just received a cancer chemotherapy. Pulsed-field gel electrophoresis, performed in 9 cases, showed an identical DNA pattern of MRSA in 7 cases, indicating a nosocomial infection. Our method to prevent spread of MRSA targeting solely the patients with MRSA infection was obviously unsatisfactory. We should target also the cases of MRSA colonization and make an effort to wash hands more vigorously. Furthermore, radical reformation such as increasing single sick-rooms drastically and increasing the number of nursing staff is also required. PMID- 11766377 TI - [Clinical characterization of blaIMP positive gram-negative rods isolated cases]. AB - We detected the metallo-beta-lactamase gene blaIMP positive strains of the gram negative rods (GNR) isolated in Oita Medical University Hospital between 1993 and 1999 and studied the clinical characteristics of patients infected or colonized with blaIMP positive GNR. 25 strains (20 Pseudomonas aeruginosa and 5 Serratia marcescens) were detected and most of them were isolated from urinary samples after 1997. In the studies of antimicrobial susceptibility, some strains had sensitivity to aztreonum or imipenem although most of the strains showed multidrug resistance. When blaIMP positive GNR were isolated from patients, these strains were thought to have caused infection in 88% of the patients. About half of the patients were over 65 years old and had malignant diseases. Most of the patients had inserted urinary tract catheters, intratracheal tube or intravernous catheters. It was suggested that the insertion of the catheters were related to infection of blaIMP positive GNRs. Two patients were not treated with any antibiotics before the isolation of blaIMP positive GNRs although more than half of the patients were administered carbapenems and cephems. Most of strains were isolated in the same department and showed the same genotype by pulsed field gel electrophoresis. PMID- 11766378 TI - [Detection of TDH-producing Vibrio parahaemolyticus O3:K6 from naturally contaminated shellfish using an immunomagnetic separation method and chromogenic agar medium]. AB - We attempted to isolate TDH-producing Vibrio parahaemolyticus O3:K6 from shellfish. Asari samples were incubated with TSB supplemented with 2% (w/v) NaCl for 6 h, and then the 6-h cultures were incubated with salt polymyxin broth for 18 h. After the two-step enrichment, a 1 ml portion of the culture was treated with magnetic beads coated with K6 antibody for immunoconcentration of V. parahaemolyticus O3:K6. The immunoconcentrated and untreated cultures were plated onto a chromogenic agar and TCBS agar media for isolation of V. parahaemolyticus. TDH-producing V. parahaemolyticus O3:K6 was isolated from 3 out of 66 lots (4.5%) of naturally contaminated Asari. Six of 4,265 colonies suspected as V. parahaemolyticus (0.14%) were TDH-producing V. parahaemolyticus O3:K6. PMID- 11766379 TI - [Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method]. AB - We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens. PMID- 11766380 TI - [A case of diffuse panbronchiolitis with SLE complicated by fungal infection]. AB - We report a patient who developed SLE during the course of diffuse panbronchiolitis (DPB) and had candidiasis later. The patient fulfilled the criteria for diagnosis of SLE after appearance of fever and general peripheral arthritis. Regarding serum virus antibody values at the time of SLE diagnosis, IgG and IgM of human Parvovirus B19 (B19) were positive by the EIA test and also by the serum PCR test. For continuously Pseudomonas aeruginozae in sputum cultures because of existing DPB, immunosuppressasnt therapy with prednisolone and mizoribine was given while suppressing proliferation of bacterial infections with antibiotics. As a result, the intensity of SLE decreased smoothly. About 1 month after beginning of the treatment, the chest X-ray revealed infiltrative densities in the lingual area of the left lobule and in S3 of the right lobule. Judging from the clinical course and various examination findings, concurrence of candidiasis was suspected. Fungal infection in this patient was progressive, so various antifungal agents were used concurrently. Furthermore, immunoglobulin therapy was supplemented while determining serum immunoglobulin levels, and doses of prednisolone and mizoribine were reduced rapidly. Afterward the patient followed a satisfactory clinical course. About 2 years later SLE recurred, aspergillosis developed concurrently and the disease progressed rapidly to its termination. DPB itself is difficult to control and often complicated with various diseases. Therefore, immunosuppresant therapy for complications is sometimes used in addition to the treatment of DPB. More careful observations on the clinical course are necessary in dealing with this disease. PMID- 11766381 TI - [Acute subdural abscess due to mixed infection of Eikenella corrodens and Streptococcus constellatus]. AB - Eikenella corrodens is a gram-negative, facultative anaerobic rod that frequently exists as part of normal human flora in the upper respiratory tract and gastrointestinal tract. Recently, E. corrodens is reported as a rare causative agent of empyematic lesion. We report a case of 10-year-old girl with acute subdural abscess. She developed a high grade fever, swelling of the left periorbital area, right sided partial seizure and hemiplegia. Brain CT and MRI showed left parietal subdural abscess. Because intravenous antibiotic therapy was not effective enough and her neurological symptoms progressed, surgical drainage was performed in order to decompress the brain and to determine the causative agents. Through careful bacterial cultures, E. corrodens and Streptococcus constellatus were detected from the subdural abscess. After the drainage operation and a three week course of appropriate chemotherapy, the abscess completely disappeared and no sequela remained. PMID- 11766382 TI - [A pediatric case of acute focal bacterial nephritis; comparison with the reports in Japanese child cases]. AB - We report an 8-year-old boy with acute focal bacterial nephritis (AFBN). At the age of 3 months, he had a history of urinary tract infection and vesicoureteral reflux. He was admitted to our hospital because of high fever and costovertebral angle pain. Although acute pyelonephritis was suspected, neither pyuria nor cultures of blood and urine were positive. An initial ultrasonogram (US) of his kidneys was normal except for bilateral hydronephrosis. Two days later, however, a computed tomography (CT) revealed a poorly enhanced mass in the upper pole of the right kidney. Similar findings were also observed by US. Under the diagnosis of AFBN, he received antibiotics for 3 weeks. Voiding cystourethrogram showed both-sided vesicoureteral reflux and he underwent an operation. At present the mass of the kidney still remains, albeit its size tends to decrease. We suggest that an early examination of US or enhanced CT is necessary in cases with fever of unknown origin, considering the possibility of AFBN even if neither pyuria nor cultures of urine are positive. PMID- 11766383 TI - [A case of severe adult measles pneumonia--efficacy of combination of steroid pulse therapy, high-dose vitamin A and gamma globulins]. AB - A 33 year-old female was admitted with facial, trunk and limb eruptions, conjunctiva intrahemorrhage, Koplik's spots in the pharynx and severe hypoxemia after fever and upper respiratory tract symptom. Infiltrative shadow of the whole right lung was seen on chest radiography. Fine crackles were seen in the lower left lung and in the whole right lung. Severe inflammation and liver dysfunction were indicated by blood test. Measles antibody IgM was high. The abnormal interstitial shadows were confirmed in greater detail by chest computed tomography. Her condition was diagnosed as measles pneumonia. A combination therapy with steroid pulse, high dose vitamin A, and gamma globulin was started, after which the patient gradually improved, indicating the effectiveness of this combination therapy for severe adult measles pneumonia. PMID- 11766384 TI - [Significance of constitutive expression of hypoxia-inducible factor-1 alpha (HIF 1 alpha) protein in pancreatic cancer]. PMID- 11766385 TI - [Immunohistochemical distributions of NMDA receptor channel subunits in the synaptic glomeruli of adult mouse cerebellum]. PMID- 11766386 TI - [Portal venous hemodynamics after living-related liver transplantation with pulsed Doppler ultrasound]. PMID- 11766387 TI - [Influence of aging in measurement of COP displacement with external stimuli]. PMID- 11766388 TI - [Identification of a novel MCC-homologue, MCC2, which interacts with PDZ-domain protein AIE-75]. PMID- 11766389 TI - [Effect of osteopontin alleles on zymosan induced liver inflammation]. PMID- 11766390 TI - [Effects of steroid therapy on long-term canal prognosis and activity in the daily life of vestibular neuronitis patients]. AB - We studied 28 patients with vestibular neuronitis treated at our hospital between 1997 and 1999. To determine the effects of steroid therapy on long-term canal prognosis and daily activity, we examined caloric tests and gave questionnaires to 12 steroid-treated and 16 nonsteroid-treated patients 2 years after onset. We found that canal improvement was 50% in the nonsteroid-treated group and 75% in the steroid-treated one. In cases with severe canal paresis (CP > or = 60%), canal improvement was 33% in the nonsteroid-treated group and 67% in the steroid treated one. Steroid therapy at the acute stage of this disease significantly reduced the duration of spontaneous nystagmus and handicap in daily life due to dizziness induced by head and body movement, decreasing mood disturbance. PMID- 11766391 TI - [Efficacy of tonsillectomy on psoriasis and tonsil histology]. AB - Treatment outcomes of tonsillectomy were studied in 7 Japanese patients with psoriasis--3 males and 4 females aged 9 to 46 years (median: 23 years)--followed up 2 to 9 years after tonsillectomy. All skin lesions disappeared in 3 patients, 80% of those in 2, and no change in the remaining 2 during follow-up. Of 5 in whom skin lesions improved, 4 were females and had a history of tonsillitis making skin lesions worse. In quantitative immunohistologic analysis on tonsillar tissues by CD20 and anti-ssDNA antibodies, areas of T cell-nodules were significantly expanded, but those of the B-lymphoid follicles were smaller, and the number of apoptotic cells increased in tonsils from patients with psoriasis and PPP compared to those with recurrent tonsillitis. The area of T cell-nodules and the number of apoptosis cells were significantly larger in tonsils from 4 patients with complete recovery after tonsillectomy compared to the remaining 9 without complete recovery. This suggests that histologic evaluation may be helpful in estimating the effectiveness of tonsillectomy. PMID- 11766392 TI - [Analysis of 200 university hospital hearing aid clinic patients]. AB - We statistically studied patients who visited our hearing aid clinic to determine what segment of the population may benefit from hearing aids. Subjects were 200 patients from 5 to 89 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, Nagoya University Hospital, between January 1998 and March 2000. This clinic lent out hearing aids. Subjects were divided into 2 groups those having their own hearing aids either new or earlier (HA group) and those giving up hearing aids after a trial (non-HA group). Mean better hearing levels in pure tone average were 50.6 dB in the HA group and 44.5 dB in the non-HA group. Mean better maximum speech recognition scores were 81.5% in the HA group and 85.3% in the non-HA group. The distribution of better hearing has shown that patients with mild hearing loss (better pure tone average < 40 dB) account for more than a quarter of all hearing aid clinic patients. Among patients with mild hearing loss, 60% had their own hearing aids. The need for rehabilitation in the mild hearing loss population thus appears large. Their intent to wear hearing aids influenced whether patients agreed or declined hearing aids after a trial. The period from use until patients made a decision was 2 weeks in 65% of those declining use and 35% of those agreeing to use. Over 15% of those agreeing called for a trial period longer than 8 weeks. Hearing aid trials provide useful information for both patients and surgeons before choosing surgery for a difficult ear condition. In this research, 18 patients needed counseling about both amplification and surgery. Bridging between ear surgery and hearing aid wearing is a vital role of hearing aid clinics at university hospitals. PMID- 11766393 TI - [Secretion and dynamics of herpes simplex virus in tear and saliva of patients with Bell's palsy]. AB - Herpes simplex virus (HSV) involvement has been clarified as the cause of Bell's palsy by molecular biological techniques. To clarify the direct relationship between virus reactivation and paralysis development, both detection of the virus genome by DNA-diagnostic and quantitative analysis of its time-course change are needed. Using polimerase chain reaction (PCR) method and microplate-hybridization combined, we detected the virus genome in small amount of specimens from patients with Bell's palsy, quantified its number of copies, and examined time-course changes. We attempted to type of HSV in positive specimens. Subjects were 16 patients with Bell's palsy positive for serum anti-HSV IgG antibody (enzyme immunoassay) who visited the outpatient clinic of Department of Otorhinolaryngology, Itabashi Hospital, Nihon University School of Medicine, within 14 days after onset without having any treatment. Tears and saliva from the parotid gland and the submaxillary gland were separately collected from the affected side and healthy side twice or more. A total of 244 specimens was subjected to DNA extraction, PCR, and microplate-hybridization, and HSV DNA was detected in 38 specimens (11.8%) from 5 patients (31%). From sampling time, the highest detection (28.5%) was obtained within 2 weeks after onset. Detection at 3 weeks and later (2.8%) was significantly lower (p < 0.05). DNA was also found on the healthy side, but in comparison between sides, detection on the healthy side (18.9%) was significantly lower than that on the affected side (83.8%) (p < 0.01). In quantitative determination of the virus genome, the amount (number of copies) was large on the affected side and largest early after onset regardless of the clinical course. Positive specimens underwent HSV-typing, and HSV-1 was found in all of them, suggesting that HSV-1 reactivation is a cause of Bell's palsy. PMID- 11766394 TI - [A case of pediatric recurrent acute mastoiditis caused by penicillin-resistant Streptococcus pneumonia complicated by primary immunodeficiency]. AB - Penicillin-resistant Streptococcus pneumoniae (PRSP) is a frequently detected pathogen of intractable acute otitis media and is associated with prolonged or recurrent infection. The use of antibiotics has made the incidence of secondary acute mastoiditis following acute otitis media relatively rare, but when it does occur, its severe complications may be life-threatening. We report a case of pediatric recurrent acute mastoiditis caused by PRSP in a 6-year-old boy suffering from PRSP acute mastoiditis on 4 occasions, twice undergoing simple mastoidectomy. Although we initially suspected PRSP to be the chief factor in iterative infection, immunological analysis demonstrated significantly decreased IgG and IgA antibodies in serum and the patient was diagnosed as having common variable immunodeficiency (CVID). As the first middle ear infection occurred at the age of 6 and there was no history of upper respiratory tract infection, CVID may be the main pathological factor of recurrent mastoiditis, although infection occurred, only in the ear and did not involve other organs. This suggests that recurrent mastoiditis in the present case involved the coexistence of PRSP and CVID. PMID- 11766395 TI - [Infection of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in acute tonsillitis--histopathological assessment by optical and electron microscopic observation of biopsy specimens of tonsils]. AB - Infection with HSV or EBV was studied by measuring serum antiviral antibody titers in adults with acute tonsillitis, and results were compared to light and electron microscopy findings of tonsil biopsy specimens. The clinical and laboratory features of acute tonsillitis caused by HSV or EBV were also studied. Subjiects were 42 patients with acute tonsillitis treated at the Department of Otorhinolaryngology at Tokyo Women's Medical University Daini Hospital between August 1997 and March 2000. They had failed to respond to antimicrobial agents prescribed by a physician, and had severe oropharyngeal mucosal lesions, liver dysfunction, skin eruptions, or cervical lymphadenopathy, with hospitalization required because of impaired food intake due to sore throat or deterioration in general condition. Subjects were 24 men (mean age: 30.8 years) and 18 women (mean age: 28.3 years) aged 16 to 78 years (mean: 29.8 years). A underwent, bacteriological and hematology tests and palatine tonsil biopsy specimens were obtained to examine tissue changes by light microscopy and electron microscopy due to detect HSV antigen by immunohistochemistry and EBV nucleic acids by EBV encoded small nuclear RNA 1 and 2 (EBER) in situ hybridization (ISH). Among patients, the serum antiviral antibody profile indicated that 4 (9.5%) had acute tonsillitis due to primary HSV infection and 5 (11.9%) had acute tonsillitis due to primary EBV infection. The findings characteristic of acute tonsillitis due to primary HSV infection included stomatitis, skin eruptions, atypical lymphocytes, and liver dysfunction. Findings characteristic of acute tonsillitis due to primary EBV infection included petechiae of the soft palate, an increase of lymphocytes, atypical lymphocytes, and liver dysfunction. At the initial test, serum anti-HSV antibody was positive in 14 patients (33.3%), and more than half had no history of prior infection. Anti-EBNA antibody was positive in 32 (76.2%), and many had been infected previously. It should be noted that a decrease in positive HSV antibody means that acute tonsillitis due to primary HSV infection is not uncommon in adults and is expected to increase steadily. Light microscopy revealed histological changes in 2 patients. HSV antigen was positive in 2 (50%) with acute tonsillitis due to primary HSV infection, while EBER cells were positive in 5 (100%) with acute tonsillitis due to primary EBV infection, so special staining of the tissues was found to be useful. Electron microscopy failed to detect viral particles in ultrathin sections and no differences were seen in morphological changes or tissue damage between patients with positivity for HSV antigen and with EBER-positive cells. Detection of HSV antigen and EBV nucleic acids in pathological specimens from patients with acute tonsillitis requires careful judgment, but is considered useful for making an early diagnosis and for making a diagnosis in patients without an increase of the antiviral antibody titer and in those with reinfection or reactivation. Pathological examination (including special staining) and careful observation of clinical features may help to identify HSV or EBV infection and allow decisions to be made with regard to the therapeutic strategy and prevention of complications. PMID- 11766396 TI - [Fatty liver quantification with line scan echo planar spectroscopic imaging (LSEPSI)]. AB - INTRODUCTION: Although fatty infiltration of liver is a benign process that generally results from chronic alcohol uptake or obesity, such lifestyle factors may lead to chronic disease. Measuring the fat concentration in liver may therefore prove useful in assessing disease status. In this study, we report the usefulness of line scan echo planar spectroscopic imaging (LSEPSI) for this problem. METHODS: Rapid successive column sampling was accomplished using orthogonal slice-selective 90 degrees and 180 degrees pulses and echo planar spectral/spatial encodings. Phantom and clinical studies of 13 patients suspected of having fatty liver were carried out with LSEPSI. Estimated fat fractions obtained with LSEPSI were compared with ultrasound findings. RESULTS: The results showed a good correlation between the actual fat content of phantoms and the estimated fat fraction obtained with LSEPSI (r = 0.95). In the clinical study, the estimated fat fraction tended to rise as the US grade of fatty liver increased. DISCUSSION: LSEPSI is largely free from T1 and T2 relaxation owing to its infinite TR and minimal T2 weighting. Thus, there is no need for relaxation analysis. In addition, the lack of phase encoding reduces motion-related ghosting artifacts. Rapid fat/water spectral quantification of liver with this technique is useful for fatty liver assessment in a clinical setting. PMID- 11766397 TI - [New detection method for small and very small gastric carcinoma using brightness curve analysis with double contrast radiography]. AB - The purpose of this study was to find an indexing feature for small gastric carcinoma taken by double contrast radiography, and to propose a new method for detecting lesions. We considered the method from the viewpoint of the detection and diagnosis of lesions. The inclination curve of the density of a small gastric carcinoma, Type IIc + IIa, with a depth of cancerous invasion of M, taken by the double contrast method was investigated. The curve of density that was obtained clearly showed the change and inclination of density that was proper for the shape of the surface of the lesion and seemed to be good for pointing out the lesion and for reproducing a new image of the lesion. Our results were as follows: The area surrounding the depressed lesion appeared as a steep-gradient brightness curve (with or without surrounding raised margin), and the frequency brightness-curve of the bottom of the lesion showed less frequency than that of the surrounding non-cancerous region. These results indicate that this proposed method is effective for the detection of small gastric carcinoma taken by double contrast radiography, although the process of elimination of false positives should be improved. PMID- 11766398 TI - [A case of metastatic breast cancer showing extraosseous accumulation of 99mTc HMDP in axillary lymph nodes on bone scintigraphy]. AB - We report a case of metastatic breast cancer that showed extraosseous accumulation of 99mTc-HMDP in left axillary lymph nodes on bone scintigraphy. Our patient had a giant left breast mass and multiple lymph node metastases with atypical calcifications. It is known that breast cancer sometimes is positively visualized as extraosseous accumulation on bone scintigraphy. Accumulation to metastatic lymph nodes of breast cancer has rarely been reported. It is suggested that bone scintigraphy is of benefit in detecting the metastatic lymph nodes of breast cancer as a screening or follow-up method. PMID- 11766399 TI - [MALT-type lymphoma of the lacrimal gland: a case report]. AB - We report a rare case of MALT-type lymphoma of the lacrimal gland in a 29-year old woman. CT scan demonstrated a solid homogenous mass in the right lacrimal gland fossa and the palpebral lobe of the lacrimal gland with contrast enhancement. The mass displayed slight hyperintensity on T1-weighted images and hyperintensity on T2-weighted images with fat saturation. The mass demonstrated an arc-like contour, and involved both the palpebral lobe and orbital lobe of the lacrimal gland. These characteristic findings may be helpful in the diagnosis of this malignancy. PMID- 11766400 TI - [Formation mechanism of 4,4-methylenebis(N,N-dimethylaniline) by the anodic oxidation of N,N-dimethylaniline]. AB - Preparative constant-current electrolysis of N,N-dimethylaniline(100 mM, DMA) was carried out in dry acetonitrile containing Et4NClO4 to give N,N,N',N'-tetra methylbenzidine(TMB) and 4,4'-methylenebis(N,N-dimethylaniline) (MDMA). In the presence of HCl, DMA was quantitatively oxidized to TMB. Formation mechanism of MDMA was discussed using the results of semi-empirical calculations that were PM3 and AM1. The proposed mechanism by Hand and coworker was ruled out and an alternative one is suggested as follows. DMA undergoes one-electron oxidation at the anode and gives the corresponding N,N-dimethylaniline cation (A). Aydroxy ion, instead of DMA, abstracts a proton from A and gives H2O and methyl(phenyl)aminomethyl radical (B). B reacts with DMA to give a 1 dimethylamino-4-(N-methyl-N-phenylamino)methyl-2,5-cyclohexadienyl radical (I). The radical I decomposes to N-methylaniline and a 1-dimethylamino-4-methylene-2,5 cyclohexadienyl radical (J). The radical J reacts with DMA to give a 1 dimethylamino-4-(4-dimethylaminobenzyl)-2,5-cyclohexadienyl radical (K), which is oxidized to MDMA by the anode. PMID- 11766401 TI - Fruits of human genome project and private venture, and their impact on life science. AB - A small knowledge base was created by organizing the Human Genome Project (HGP) and its related issues in "Science" magazines between 1996 and 2000. This base revealed the stunning achievement of HGP and a private venture and its impact on today's biology and life science. In the mid-1990, they encouraged the development of advanced high throughput automated DNA sequencers and the technologies that can analyse all genes at once in a systematic fashion. Using these technologies, they completed the genome sequence of human and various other organisms. These fruits opened the door to comparative genomics, functional genomics, the interdisprinary field between computer and biology, and proteomics. They have caused a shift in biological investigation from studying single genes or proteins to studying all genes or proteins at once, and causing revolutional changes in traditional biology, drug discovery and therapy. They have expanded the range of potential drug targets and have facilitated a shift in drug discovery programs toward rational target-based strategies. They have spawned pharmacogenomics that could give rise to a new generation of highly effective drugs that treat causes, not just symptoms. They should also cause a migration from the traditional medications that are safe and effective for every members of the population to personalized medicine and personalized therapy. PMID- 11766402 TI - [Cytokines and chemokines: mediators for intercellular communication in the brain]. AB - The brain includes glial cells (astrocytes, microglia and oligodendrocytes) and endothelial cells in addition to neurons. Under some pathological conditions, it is invaded by leukocytes such as neutrophils, monocytes/macrophages and lymphocytes. Intercellular communication across these cell species is supposed to play crucial roles both in the brain functions and dysfunctions. However, the molecular basis of such intercellular communication remains unclear. We have studied the roles of cytokines and chemokines, which have been investigated as essential mediators in the immune and inflammatory systems, in intercellular communication across neurons, glial cells, endothelial cells and leukocytes. Messenger RNA expression of cytokines such as interleukin-1 beta was induced in brain microglia by i.p. injection of excitotoxin and neurostimulant, at least, partly via catecholaminergic systems. Messenger RNA of other cytokines such as leukemia inhibitory factor was induced in astrocytes. This cytokine specifically induced nociceptin mRNA in the cultured cortical neurons. Constitutive expression of some chemokines such as fractalkine and stromal cell derived factor-1 alpha was observed in the brain, suggesting that they play important roles in maintenance of brain homeostasis or determination of the patterning of neurons and/or glial cells in the developing and adult brains. Cytokines such as interleukin-1 beta and chemokines such as monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha were produced in ischemic brain and implicated in ischemic brain injury. In addition to ischemia, cytokines, chemokines and their receptors have been shown to be involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease and AIDS dementia syndrome. They are potential targets for therapeutic intervention for neurodegenerative diseases. PMID- 11766403 TI - [Development of boomerang-type intramolecular cascade reactions and application to natural product synthesis]. AB - Intramolecular cascade reaction has received much attention as a powerful methodology to construct a polycyclic framework in organic synthesis. We have been developing "boomerang-type cascade reaction" to construct a variety of polycyclic skeletons efficiently. In the above reactions, a nucleophilic function of substrates changes the character into an electrophile after the initial reaction, and the electrophilic group acts as a nucleophile in the second reaction. That is, the reaction center stepwise moves from one functional group back to the same one via other functional groups. The stream of the electron concerning the cascade reaction is like a locus of boomerang. We show here three different boomerang-type reactions via ionic species or free radicals. 1) Diastereoselective Michael-aldol reaction based on the chiral auxiliary method and enantioselective Michael-aldol reaction by the use of external chiral sources. 2) Short and efficient total syntheses of longifolane sesquiterpenes utilizing intramolecular double Michael addition as a key step. 3) Development of boomerang-type radical cascade reaction of halopolyenes to construct terpenoid skeletons and its regioselectivity. PMID- 11766404 TI - [Cellular and molecular pharmacological studies on membrane receptor-signaling and stress-responses in the brain]. AB - Studies on the cellular and molecular mechanism of neurotransmitter receptor signaling and of neuronal and glial cell responses to stresses seem to be important to elucidate the action mechanism of centrally-acting drugs and to develop novel therapeutics against several diseases in the brain. The present review shows our findings with regard to the membrane receptor-signaling mechanism including serotonin, noradrenaline, glutamate receptors, ion channels, G-proteins, protein kinases and drug actions in Xenopus oocytes injected with rat brain mRNA, NG108-15 cells and brain membranes. Regarding the results of studies on the inter- and intra-cellular mechanism of neurons and glial cells against cerebral ischemia/hypoxia, we review the involvement of a transcription factor NF kappa B in LPS-elicited inducible NO synthase (iNOS) expression in rat astroglial cells. Then we describe possible involvement of: 1) ADP ribosylation/nitrosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 2) decrease in mitochondrial membrane potential, release of caspase-3 from mitochondria and degradation of the inhibitor of caspase-activated DNase by activated caspase in NO-induced neuronal apoptosis. We observed that hypoxia results in expression of a molecular chaperon such as protein disulfide isomerase (PDI) and HSP70 in astroglial cells. Our recent findings indicate that overexpression of PDI in the rat hippocampus (in vivo) and in neuroblastoma SK-N MC cells (in vitro) significantly suppress the hypoxia-induced neuronal death. From physiological/pathophysiological and pharmacological aspects, we review the importance of studies on the cellular and molecular mechanism of membrane receptor-signaling and of stress-responses in the brain to identify functional roles of neuro-glial- as well as neuro-neuronal interaction in the brain. PMID- 11766405 TI - [Modification of morphine dependence under chronic pain and its mechanism]. AB - Clinical studies have demonstrated that when opiates are used to control cancer pain, psychological dependence and analgesic tolerance are not a major concern. The present study was, therefore, designed to investigate the modulation of rewarding effects of opiates under inflammatory chronic pain in SD rats. Formalin (2.5%, 50 microliters) or carrageenan (1%, 100 microliters) was injected into the plantar surface of the rat paw. Formalin and carrageenan reduced the paw pressure threshold. The hyperalgesia lasted for 9 to 13 days. Rewarding effect of morphine was evaluated by conditioned place preference paradigm. Morphine produced a significant place preference. This effect was significantly attenuated in inflamed groups as compared with the respective non-inflamed groups. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. On the other hand, we found that kappa-opioid receptor agonists markedly inhibit rewarding effect of mu opioid receptor agonists. Therefore, to elucidate the mechanism of this attenuation, the effects of pretreatment with kappa- and delta-opioid receptor antagonists, nor-binaltorphimine (nor-BNI) and naltrindole (NTI), on the development of the morphine-induced place preference under inflammation were examined. Nor-BNI, but not NTI, eliminated the suppression of the morphine induced place preference in inflamed groups. The morphine-induced increase in dopamine turnover in the limbic forebrain was suppressed under inflammation, and the suppression was abolished by the pretreatment with nor-BNI. These results suggest that endogenous kappa-opioid systems may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by morphine. PMID- 11766406 TI - [New orally active penem antibiotic: Farom]. AB - An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum beta-lactamase (ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1,3-butanediol. The synthetic intermediate, a 3-hydroxyethyl 4-acetoxyazetidinone derivative, was efficiently prepared by the 2 + 2 coupling of a optically active vinylsulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position. PMID- 11766407 TI - [Improvement of transmucosal absorption of biologically active peptide drugs]. AB - Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract or impermeable through the intestinal mucosa. For the systemic delivery of the peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, this administration is poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various approaches have been examined to overcome the delivery problems of these peptides when they are administered into the gastrointestinal tract and other mucosal sites. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. In this study, we demonstrated that the transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by the use of these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs. PMID- 11766408 TI - [Development and application of enantioselective Lewis acid-Lewis base bifunctional catalyst]. AB - The design, synthesis, and application of a new bifunctional enantioselective catalyst containing both Lewis acidity and Lewis basicity are described. Recent developments of chiral quaternary stereocenter synthesis through catalytic enantioselective Reissert-type reaction and cyanosilylation of ketones forming the S-enantiomer are chiefly reviewed. The catalysts are composed of a Lewis acid metal (aluminum, titanium, or lanthanide) and a Lewis base (the oxygen atom of a phosphine oxide), of which positions are defined by 2,2'-binaphthol (BINOL) or a carbohydrate scaffold. Utilizing these catalysts, we have developed a variety of enantioselective cyanation reactions, such as cyanosilylation of aldehydes and ketones, Strecker-type reaction, and Reissert-type reaction. These reactions showed a broad substrate generality. Investigations toward the elucidation of the reaction mechanism, involving kinetic studies, comparison of the results by control catalysts, and absolute configurations of the products, revealed that these reactions are catalyzed by a dual activation of a substrate and trimethylsilyl cyanide (TMSCN) by the Lewis acid and the Lewis base of these catalysts. Catalytic enantioselective synthesis of several drug lead compounds, such as anti-cancer epothilones, potent N-methyl-D-aspartate (NMDA) receptor antagonists, phenytoin analogs, salsolinol carboxylic acid, and anti-cancer camptothecin was achieved, using these reactions as key steps. PMID- 11766409 TI - [Nickel-catalyzed [2 + 2 + 2] cocyclization and its application to the synthetic organic chemistry]. AB - A nickel (0)-catalyzed asymmetric [2 + 2 + 2] cocyclization has been realized for the first time. This reaction involves conceptually new enantiotopic group selective formation of a nickelacyclopentadiene intermediate and produces an isoindoline derivative (73% ee, 78% conv. yield) and an isoquinoline derivative (54% ee, 62% yield) having benzylic chiral carbon centers. The synthesizing methods of biaryls using the nickel-catalyzed [2 + 2 + 2] cocyclization were also developed. Two ways for the synthesis of biaryl using [2 + 2 + 2] cocyclization were investigated: one method is that biaryls synthesized from alkyne having a phenyl group and 2 equivalents of acetylene, and the other method is that those were synthesized from alpha,omega-diyne having a phenyl group at the alpha position and acetylene. PMID- 11766410 TI - [The chemistry of cyclazines]. AB - This review summarizes our studies on the development of the syntheses of cyclazine derivatives. These studies involve the following four main subjects; 1) the studies on cycl[3.2.2]azine derivatives; 2) the studies on cycl[3.3.2]azinone derivatives; 3) the studies on azacycl[3.3.3]azine derivatives; 4) the studies on cyclazinophane derivatives. PMID- 11766411 TI - Enantioselective uptake of BOF-4272, a xanthine oxidase inhibitor with a chiral sulfoxide, by isolated rat hepatocytes. AB - The transport mechanisms of the enantiomers of BOF-4272, a new drug for the treatment of hyperuricemia, were studied using freshly prepared rat hepatocytes. BOF-4272 consists of S(-) and R(+) enantiomers due to a chiral center in the sulfoxide moiety. The uptake of these BOF-4272 enantiomers by hepatocytes was found to be temperature and dose dependent. The temperature-dependent uptake of the S(-) and R(+) enantiomers showed saturation kinetics. The Km values for the S(-) and R(+) enantiomers were 59.3 and 25.7 microM, respectively, which was a significant difference (p < 0.05). However, the maximal uptake rate was comparable for both enantiomers. Metabolic inhibitors such as antimycin, oligomycin, rotenone, carbonylcyanide m-chlorophenyl hydrazone, and carbonyl cyanide-p-(trifluromethoxy)-phenylhydrazone significantly inhibited uptake of the R(+) enantiomer, but had little effect on uptake of the S(-) enantiomer. Ouabain (an inhibitor of Na+/K(+)-ATPase) and p-nitrobenzylthioinosine (NBMPR, a nucleoside transporter inhibitor) showed no significant effects on the uptake of either enantiomer. Organic anions such as taurocholate and cholate reduced the uptake of both enantiomers. These results suggest that the hepatic uptake of both BOF-4272 enantiomers is not due to simple diffusion but also involves carrier mediated uptake. We suggest that the carrier-mediated uptake of BOF-4272 enantiomers includes both NBMPR-insensitive facilitated diffusion and an active transport system in liver plasma membrane, and that the enantioselective uptake of BOF-4272 is due to differences in affinity for the active transporter. PMID- 11766412 TI - The participation of pharmacists in a team to introduce a clinical pathway to laparoscopic cystectomy in obstetrics and gynecology. AB - In the Department of Obstetrics and Gynecology at our hospital, a team of doctors, pharmacists, nurses, and other medical staff was established to prepare a clinical pathway for laparoscopic cystectomy. Various data on clinical charts including the use of drugs were collected from 57 patients by pharmacists and nurses. Based on the analysis of these data, hospitalization period, method of preoperative bowel preparation, time to initiation of food intake, duration of antibiotic administration, and time and content of pharmaceutical instructions to patients of dosage and administration were determined. Criteria for variances requiring the doctor's directions were determined for fever, wound pain, and vomiting. The clinical pathway established here allows of not only the efficient and uniform care of patients, but also the active exchange of opinions among members of the medical team. Moreover, most patients who replied to a questionnaire said that they were at ease during hospitalization because they had received detailed information about the clinical pathway including the use of drugs before surgery. Thus, the participation of pharmacists on a medical team that is introducing a clinical pathway is particularly important because the use of drugs and pharmaceutical care are an important part of good patient care. PMID- 11766413 TI - Current perspectives on the medical use of marijuana. PMID- 11766415 TI - HIV affinity hemodialysis as a treatment for AIDS. PMID- 11766414 TI - The promising voyage of SNP target discovery. PMID- 11766417 TI - Polyoma virus JC DNA detection by polymerase chain reaction in CSF of HIV infected patients with suspected progressive multifocal leukoencephalopathy. AB - Several studies had previously demonstrated the high sensitivity and specificity of JCV DNA detection in CSF by PCR. This paper reported the implementation of a simple PCR procedure to detect JCV in the CSF in a cohort of HIV-1 infected patients from Argentina. Years ago, the confirmatory diagnosis of this disease was made by in-situ hybridization or immunohistochemistry techniques on brain biopsies. The PCR procedure described here improves the diagnosis of PML because it is simple and noninvasive, and allows the differential diagnosis of PML from other neurological syndromes associated with AIDS. Many recent studies report a significant benefit of combined antiretroviral therapy on the survival of HIV patients without clear neurological improvements. A negative correlation has been described between the concentration of JCV in the CSF and survival time in HIV-1 infected patients, and the level of immune depression may influence JCV replication. This suggests that a single CSF JCV viral load determination during the course of PML disease progression may be of prognostic value for managing HIV patients. PMID- 11766416 TI - Diagnosis, evaluation, and treatment of HIV/HCV coinfection. PMID- 11766418 TI - Ferrovir: a new antiviral drug for the treatment of HIV. PMID- 11766419 TI - Bacteriophage-based technologies for the rapid diagnosis and drug susceptibility testing of tuberculosis. PMID- 11766420 TI - Focus on cardiac care at AACC '01. PMID- 11766421 TI - A stepwise approach to evaluating new drug therapy. PMID- 11766422 TI - Applying the new cholesterol guidelines to your practice. PMID- 11766423 TI - What you and your patients should know about herbal medicines. PMID- 11766424 TI - A burning pruritic rash on the abdomen. PMID- 11766425 TI - Therapeutics in an age of information overload. PMID- 11766426 TI - Educating the organization. PMID- 11766427 TI - The power of PKI (Public Key Infrastructure). PMID- 11766428 TI - One and done. The use of biometrics and authentication technologies can help healthcare organizations reduce workflow costs while safeguarding access to patient data. PMID- 11766429 TI - CIOs: their challenges and satisfactions. PMID- 11766430 TI - E-learning and the enterprise. The Eckerd Corporation brings continuing education to pharmacists nationwide with online learning. PMID- 11766431 TI - Integrated HIS for community hospitals. PMID- 11766432 TI - What works: scheduling. Integration inspiration. PMID- 11766434 TI - Security hotlist. PMID- 11766433 TI - What works: financial application. One system fits all. PMID- 11766435 TI - Long-term planning for authentication solutions. PMID- 11766436 TI - The elusive CPO (chief privacy officer). PMID- 11766437 TI - Once is enough. An enterprise-wide master patient index can eliminate duplicate entries and overlays with unique patient identifiers. PMID- 11766438 TI - Transmission tune-up. Broadband options are being adjusted to align with the growing needs in healthcare. PMID- 11766439 TI - Disease management at a crossroads. PMID- 11766440 TI - Rewards of automated testing. Identifying problems before rollout can avoid system disruption. AB - PROBLEM: Needed order management application that performed consistently and met high demands. SOLUTION: Load testing identified specific problem areas. RESULTS: Precise description of problems and their occurrence helped speed resolution and ensured successful implementation. KEYS TO SUCCESS: Testing of conditions that emulated expected demands at early stage of design and planning. PMID- 11766441 TI - Power to the PDA. PMID- 11766442 TI - Embracing the young employee: the key to the future of health care. AB - With staffing problems a common concern throughout health care, it has become critical for today's health care businesses to start taking proactive steps in recruitment and retention efforts. Many organizations are putting recruitment, selection and retention teams together to assist with their efforts toward consistent service delivery. These teams have begun to address the issues associated with the new work force. This is particularly important as it relates to dealing with younger employees joining today's organizations. If we want an organization in the future that delivers service in a quality manner on a consistent basis, without undue worry, we must tackle the young employee opportunity. PMID- 11766443 TI - Setting the standard. AB - Beginning Oct. 16, 2002, hospitals will no longer be able to submit claims to third party payers electronically unless the claims are in standard format. As a result, claims formerly submitted in UB92 (currently the defacto institutional claims standard) or other traditional formats will need to be submitted in X12N 837, which is a standard developed by the Accredited Standards Committee of the American National Standards Institute. This requirement is yet another challenge for hospitals resulting from the Health Insurance Portability and Accountability Act (HIPAA). PMID- 11766444 TI - Jump starting the future health care work force. AB - One of the busiest and most important departments in health care organizations today is human resources. As the fear of staffing shortages is becoming less of a future threat and more of a reality for many, hospitals must become creative in their approaches to recruiting and retaining health care professionals. Over the next four issues, Michigan Health & Hospitals magazine will feature four programs that are particularly innovative and are getting results. PMID- 11766445 TI - Mandatory overtime: a necessary last resort. AB - As I was asked to write an article on mandatory overtime, I thought, I'd rather not! This is one of those topics that no one wants to support; yet, some facilities have no other way of caring for their patients unless they employ mandatory overtime on an emergency basis. I then mentioned this opportunity to my CEO, Richard Young, and he commented, "It's a lot like asking pilots to continue to fly after their shift. Would we want to fly with that pilot?" PMID- 11766446 TI - Improving access to health care. AB - It is a problem that has plagued the American health care system for years, and it is not getting any better. While the majority of our population enjoys ready access to the finest health care in the world, a steadily growing number are joining the ranks of the uninsured. Despite a strong economy throughout the last decade, the uninsured rate in Michigan is at a higher level today than it was in 1990, and more than one million residents currently have no health care insurance. PMID- 11766447 TI - What's HOTT (Health Opportunities for Today and Tomorrow)? PMID- 11766448 TI - Camp with a twist. AB - Marshall's Oaklawn Hospital has created a special center, a camp of sorts, that gives its clients the ability to walk away from their experience feeling better than ever. The Total Joint Center is a collaboration between Oaklawn and several local orthopedic surgeons that gives total joint replacement patients a team atmosphere to recover in. PMID- 11766449 TI - I want to work in your hospital! PMID- 11766450 TI - Take-out training. E-learning on the menu can improve the bottom line. PMID- 11766451 TI - The remedial power of MUMPS. PMID- 11766452 TI - [Will medicine find its identity in the new century? II. Methodology in medical research and the dichotomy of medicine]. AB - Views on causality in medicine are today deeply influenced by philosophy of T. S. Kuhn (paradigm) and K. R. Popper (falsification of hypotheses). Contemporary epidemiological studies, which show the importance of social factors, move scientists in medical research to broaden their traditional positivistic reasoning with the deductive approach in the hypothesis formation, with using sociologic methods and to develop sociobiological research. From the point of falsification theory and alteration of scientific revolutions the causal way in the disease etiology in the permanent seek of the "final" link in the chain of risk factors. Medicine as a humanistic and social science developed dichotomically and asymmetrically. It is now divided and dysfunctional because it is not able to use fully its internal capacity to improve health of the whole population. Search for the identity of medicine is permanent and never ending historical process. PMID- 11766453 TI - [Peroxisomal hereditary metabolic disorders]. AB - Metabolic function of peroxisomes includes oxidation of wide spectrum of substances in the presence of oxygen. Hydrogen peroxide formed at the same time is either degraded by catalase or further utilized in peroxidative reactions. From the view of cellular pathology, the most important becomes alpha and beta oxidation of carboxylic acids, particularly beta-oxidation of long-chain carboxylic acids, which undergoes selectively in peroxisomes. Mutations of peroxisomal genes result in serious metabolic disorders. At present about twenty hereditary peroxisomal diseases has been described. One group of them includes generalized forms (impairment of peroxisome biogenesis); diseases of other group result from isolated defects of individual peroxisomal enzymes. Combined incidence of peroxisomal hereditary disorders in the Western Europe is estimated to be 1:10,000. Beside the X-linked adrenoleukodystrophy, all others have the autosomal-recessive type of heredity. In phenotypic manifestation of generalized forms, as in the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, rhizomelic chondrodysplasia punctata, an impairment of the central nervous system, liver, and kidney dominate. Most of the patients die within one year, survival period longer than three years becomes exceptional. X adrenoleukodystrophy, pseudoneonatal adrenoleukodystrophy, trifunctional enzyme deficiency, Refsum disease, primary hyperoxaluria, acatalasemia result from the deficiency of a single enzyme. The most frequent peroxiosomal hereditary disease, the X-adrenoleukodystrophy, has several clinical phenotypes, which most frequently manifest already in infants. The disease has also a clinically less serious form, which manifest only in adults--the adrenomyeloneuropathy. For the postnatal but also for the prenatal diagnostics, methods of biochemistry, molecular genetics, morphology, and immunocytochemistry are necessary. PMID- 11766454 TI - Childhood morbidity and air pollution in the Teplice program. AB - BACKGROUND: A study of morbidity of children aged 0 to 3 years was conducted in two districts in the Czech Republic. Comparisons were made between children living in Teplice district, known for its high air pollution, and children living in Practice, a district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: The children were selected for the follow up based on deliveries from May 1994 to December 1966. Childhood morbidity during the first three years of life of 452 children was extracted from their pediatric records. Diagnoses were coded using the International Classification of Diseases--10th edition, and categorized into broad groupings. Children born in Teplice experienced a significantly higher rate of otitis media and otalgia, gastrointestinal infections, upper respiratory infections, and pneumonia, but did not differ in their risk for bronchitis or for viral infections such as varicella. These findings remained after multiple linear regression models adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts must be considered: systematic diagnostic differences for several health outcomes comparing pediatricians in Teplice vs. Practice, differences in health-care seeking behavior by the parents, and inadequate control for confounding. PMID- 11766455 TI - [Birth weight and gestational age in relation to the course of pregnancy]. AB - BACKGROUND: In midpregnancy, more than 3000 women in Brno filled in the questionnaires for the ELSPAC study. They informed of their health, activities, stress and psychological state during this pregnancy. METHODS AND RESULTS: Out of medical documentation, the results from routine prenatal examinations were extracted and records concerning all disorders occurred during the gravidity. After delivery, information coming from both sources were linked to the birth weight (BW) and gestational age (GA) data of newborns and analysis of variance was performed. In statistically significant relations the differences were stated in BW (grams) and in GA (weeks) between the group means and sample means for boys, girls and all newborns together. BW, GA or both values were significantly lower after taking some medicaments, alcohol drinking, in offsprings of mothers who felt feeble around the quickening, who worked part time, who were in leading position in their employments, who experienced serious disease, who tempted a suicide, who worried that the foetus might be handicapped in any way and who did not take their future motherhood for a priority. Heavier were newborns of women who married during pregnancy and longer GA had children of those who took folic acid. The relation of neurotic symptoms to the outcome of pregnancy was not found and stressogenic events showed only a limited effect on it. A strong deficit in BW and GA followed after premature abruption of placenta, after eclampsia, placenta praevia, cervical cerclage, partus premature imminens, bleeding in the 2nd trimester, hypertension and hospitalization, namely when repeated. BW only was lower with IUGR, oligohydramnion, and higher BW followed after oedemas. GA only was affected in those whose mothers omitted the sonographic examination and who were obliged to have a special diet. CONCLUSIONS: When newborns BWs were divided into 8 classes by 500 g and some maternal characters followed across the scale, significant trends were found in maternal heights, in all their weight indicators including maternal BW as well as in the weight gain in pregnancy, in the highest means found during pregnancy of systolic and diastolic blood pressures and in the lowest haemoglobin levels. PMID- 11766456 TI - [Phases of the menstrual cycle and therapeutic response to neuroleptic therapy in patients with schizophrenia]. AB - BACKGROUND: The low estrogen level is associated with the worsening of the psychotic symptoms in females with schizophrenia. We tested the hypothesis that the patients admitted to the hospital in low-estrogen (low-E) phase require lower neuroleptic dosage and shorter length of hospital stay than the patients admitted in the high-estrogen (high-E) phase. METHODS AND RESULTS: 51 female patients with schizophrenia were divided into two groups according to their menstrual cycle phase at admission and according to the type of neuroleptic treatment during their hospitalisation. 53% of them were admitted in the low-E phase. The Student T-test was used for the analysis. The patients of the low-E phase group had lower daily dosage of typical neuroleptics (p < 0.001), higher age (p < 0.05) and shorter length of hospital stay (p < 0.05) than the patients taking atypical neuroleptics. The patients taking typical neuroleptics in the low-E group had lower daily dosage (p < 0.05) and they were older (p < 0.01) than the patients taking typical neuroleptics in the high-E group. The shorter length of hospital stay (p < 0.001) was found in high-E patients with atypical neuroleptics than in low-E patients with atypical neuroleptics. CONCLUSIONS: Several further perspectives of estrogen-studies in schizophrenic women are discussed. PMID- 11766457 TI - [Determinants of professional status among physicians in Mexico]. AB - OBJECTIVE: This study explored a number of factors that determine the professional status of physicians in Mexico. METHODS: Using structural equation modelling techniques, causal models were developed to investigate the determinants of professional status within the medical field. RESULTS: The findings suggest that the proposed stratification process in the causal model has empirical support. In the prestige dimension, there is an adscriptive effect of gender, the resultant gender segregated the Mexican medical profession; in addition the achievement effects of medical education and work history within significant occupational and bureaucratic structures. In the economic dimension, the ascriptive effect of gender and the resultant differential in income and job opportunities of female physicians exist. CONCLUSIONS: Although social origin seems to have a weak effect on the dimensions of professional status, it is suggested that both medical education and employment history were both significant positive determinants of professional status in the Mexican medical system. On the other hand, there are still significant gender inequities in the stratification structure of the medical profession. PMID- 11766458 TI - [Early and intermediate responses as factors predicting efficiency of antidepressive agents]. AB - An important limitation in the treatment of depression is the lack of reliable factors for predicting treatment response. Most of these factors have been related to biological and clinical aspects. A clinical aspect that has proved to reasonably predict long-term efficacy is early response. An adequate early response predicts a good outcome at the long term. The purpose of this study was to quantify the proportion of patients who show no response to a fixed dose of antidepressants after 2,4, and 6 weeks of treatment, and then respond by week 8. Additionally, a subgroup of patients was followed using the same methodology until 12 weeks of treatment. A lack of response by weeks 4 and 6 predicted a final lack of response both at weeks 8 and 12 of treatment. Alternatively, a robust response as early as week 2 predicted a good response by the end of the two treatment periods. These findings should help clinicians revalorate treatment when finding no response after 4 or 6 weeks of treatment. PMID- 11766460 TI - [Analysis of HLA-DR in Mexican patients with pemphigus]. AB - Pemphigus are a group of bullous skin disorders histologically characterized by intraepidermal acantholytic and circulating antibodies blisters due to directed against the cellular surface of keratinocytes. In Mexican patients with pemphigus, HLA antigens have not been studied as they have been for other populations; for this reason, a comparative, prospective, transversal and observational study has been done with 25 patients, 18 with pemphigus vulgaris and the other seven with pemphigus foliaceus. DNA was extracted by the salting out method and HLA-DR was determined by amplification with PCR and allele specific oligonucleotides (ASO). RESULTS: HLA-DR14 (DR6) is more common in patients with pemphigus vulgaris than in the healthy population, which corroborates with previous reports. On the other hand, as reported we also found that HLA-DR1 in Mexican population represents a higher risk for pemphigus foliaceus. PMID- 11766459 TI - [Diabetes family history is associated with early insulin response, in healthy Hispanic-Mexican subjects]. AB - OBJECTIVE: To identify the associated risk factors to the increase of early insulin response in healthy Hispanic-Mexican subjects. METHODS: Comparative cross sectional study including 130 nonpregnant women and 54 men older than 30 years of age, randomly selected from Durango City, an urban population from the North of Mexico. According to the insulinogenic index value that assesses the early insulin response, subjects were distributed into quartiles. Subjects with increased insulin response (4th quartile) were compared against a control group (2nd and 3rd quartile). RESULTS: There were no significant differences by obesity (body mass index 29.2 +/- 5.1 vs. 28.7 +/- 4.5 kg/m2), nor fasting nor 2-h post dose glucose (85.2 +/- 16.1 vs 82.1 +/- 10.4 mg/dL, and 95. +/- 25.5 vs. 99.1 +/- 23.1 mg/dL) between subjects in the 4th quartile vs. subjects in the 2nd and 3rd quartile, respectively. The family history of diabetes (FHD) (Odds ratio 3.9; C1(95%) 1.3-9.1, p < 0.01) was a powerful risk factor associated to increased early insulin response. CONCLUSIONS: FHD is an independent predictor for increased early insulin response in Hispanic-Mexican subjects. PMID- 11766461 TI - [Etiology of deafness-hearing loss]. PMID- 11766462 TI - [Apoptosis and its biomedical significance]. AB - Cell death can occur through apoptotic or necrotic death pathways. Membrane disruption leads to inflammation, a typical feature of necrosis. Apoptosis constitutes a genetically controlled physiologic process of cell removal. It is characterized by cell shrinkage, chromatin condensation, and DNA cleavage. Apoptotic cells are rapidly recognized and engulfed by phagocytes thus inhibiting an inflammatory response following necrosis. Apoptosis has been proposed as a basic event to protect tissue homeostasis. This paper analyzes the genetic, biochemical, and morphologic characteristics related to apoptosis, as well as its relationship to certain illnesses. PMID- 11766463 TI - [A 70-year-old woman, hypertensive and diabetic, with dysuria, hematuria, and transvaginal bleeding]. PMID- 11766464 TI - [Carcinoid syndrome: report of a case with heart involvement and primary ovarian tumor]. AB - A patient with a primary ovarian carcinoid tumor with extensive carcinoid heart disease, without hepatic metastases is presents. Literature was revisited, emphasizing that carcinoid heart disease secondary to an ovarian tumor is quite rare. Surgical indications relative to this patient are discussed. PMID- 11766465 TI - [A case of Creutzfeldt-Jakob in the Mexican north-east and review of current concepts on prion disease]. AB - The case reported here is that of a 50-year-old man from Saltillo, Coahuila, Mexico, who during the previous 15 months developed a demential syndrome and myoclonia. The brain biopsy led to establish a diagnosis of spongiform encephalopathy. The EEG showed periodic sharp wave complexes over the right hemisphere. A review on about prion diseases is included. PMID- 11766466 TI - [Intercultural adaptations at hospitals for Indians in New Spain]. AB - Exclusive hospitals for attention to sick natives were founded in New Spain. The most important of these were established by Franciscan missionaries at the Valley of Mexico and by the Agustinians in Western Mexico. In addition, foundation of the hospitals towns at Michoacan's bishop, designed by Don Vasco de Quiroga, were based on the utopic and humanistic ideas of Thomas More. In this article we offer a revision of their origins, their multiple forms of economic support, the administrative operation, hospital organization with the extraordinary participation of the Indian natives the trust deposited in these institutions by the users, the peak and consolidation in the 16th and 17th centuries, as well as decadence and cancellation in the 19th century. Additionally, we carried out the review of the organization and operation with the goal of assessing the degree of realistic achievement in these institutions to render them more accessible to the appropriate social and cultural characteristics of the indigenous patients. The lessons of the past helped us not to similar mistakes again. In this vein, the knowledge and experience of those who preceded us can help us resolve actual problems. PMID- 11766467 TI - [Klippel-Feil syndrome. Three-dimensional tomographic images]. AB - Klippel-Feil syndrome (KPS) is characterized by congenital vertebral fusion believed to result from faulty segmentation along the embryo's developing axis. The hallmark phenotypic findings of low hairline, short neck, and limited range of motion of the neck are found as al triad in < 50% of patients. Congenital musculoskeletal and systemic anomalies are commonly found. These include, but are not limited to elevation of the scapula, scoliosis and renal and cardiac abnormalities. Here, we present the three-dimensional images by computed tomography of a 9-year-old boy with multiple fusion of the cervical vertebraes. PMID- 11766468 TI - [A new myotonic dystrophy gene]. PMID- 11766470 TI - [Scientist, artist, or teacher. What is needed in modern times?]. PMID- 11766469 TI - [Who smoke at a general hospital? Clinical comment]. AB - BACKGROUND AND OBJECTIVE: Tobacco consumption is a public health problem. Hospitals are not free of this circumstance because there are smokers inside these institutions; thus, it is important to identify who smoke in hospitals. METHOD AND RESULTS: A general survey with closed questions was carried out among 659 workers at a tertiary level general hospital. Smoking habit was positive in 184 employees and negative in 475. The majority of smokers were married and worked in the administrative offices, 46 of which belong to the medical area. Academic level was not an important determinant for tobacco consumption. The habit began between 10 to 20 years of age, mainly in relation with a sensation of pleasure, relaxation, and the need to smoke. CONCLUSIONS: The main site for smoking was the working area, 70% of nonsmokers are converted passive non voluntary smokers. It is important to take actions to avoid tobacco smoking in hospitals in pursuit of a hospital environment free of tobacco smoke. PMID- 11766471 TI - [Comments on the article "Study of the anti-inflammatory effect of a topical corticosteroid]. PMID- 11766472 TI - [Response to the letter about the insurance institutions specialized in health]. PMID- 11766473 TI - Forced migration. The need for a public health response. PMID- 11766474 TI - The burden of community-acquired pneumonia in Spain. AB - BACKGROUND: Community-acquired pneumonia accounts for a large number of hospitalizations and deaths in developed countries. METHODS: Data for Spain were obtained from the national surveillance system for hospital data and comprises all hospital discharges for pneumonia reported during a two-year period. RESULTS: The annual incidence of hospitalization for pneumonia was 160 per 100,000 population. Incidence of hospitalization, mortality, average length of stay and case-mortality rate were higher in persons > or = 65 years of age. The annual cost of these hospitalizations was 115 million ECUs (1 ECU = 1.19 US Dollars). CONCLUSION: Community-acquired pneumonia accounts for 53,000 hospitalizations per year in Spain, and this imposes a large economic cost on the National Health-care System. PMID- 11766475 TI - Patterns of comorbidity and the use of health services in the Dutch population. AB - BACKGROUND: The study objective was to examine the relation between combinations of chronic conditions in the same person and the volume and variety of health care utilization. METHODS: Analysis of continuous Netherlands Health Interview Survey data (1990-1997). The study population consisted of adults (16 years and older) reporting at least one chronic condition from the following six disease clusters: musculoskeletal diseases, lung diseases, neurological disorders, heart diseases, diabetes, and cancer (n = 13,806). Health care utilization is categorized in terms of contacts in the preceding year with a general practitioner (GP), medical specialist, physiotherapist, home help and/or home nursing, and hospital admission. Utilization was adjusted for age, gender and year of interview. Statistical methods used are contingency table analysis and (logistic) multiple regression. RESULTS: Almost one-fifth of the study population reported more than one chronic condition. Musculoskeletal disease, in addition to being the most common single condition, was found to be the condition most likely to occur with one of the remaining five disease clusters. Seven per cent reported not having used any services at all. Two-thirds of the study population used at least two different services in the previous year. In contrast, 26% of the study population reported comprehensive utilization patterns (GP and/or home care and/or physiotherapist and/or medical specialist and/or hospitalization: minimum of three types). Persons with more than one chronic condition reported having used more services, in terms of volume and variety, than those with only one condition. CONCLUSIONS: There is a strong association between comorbidity and the volume and variety of health care services that are used. Since many people have comorbid conditions, their use of health services is more complex than would be suggested by a one-disease approach. New disease management systems need to be developed to reflect the multiplicity of health care needs of the growing number patients with more than one chronic condition. PMID- 11766476 TI - Cost-effectiveness analysis of strategies for hepatitis C screening in French blood recipients. AB - BACKGROUND: In a context of scarce health resources and varied medical practices, the aim of this study was to compare cost-effectiveness of different screening strategies for hepatitis C virus among blood recipients. METHODS: A cost effectiveness model was used to test nine screening strategies in three survival categories. Three Markov models were used for three methods of follow-up. The marginal cost-effectiveness ratio was estimated to compare the screening strategies. RESULTS: Hepatitis C virus serology by enzyme-linked immunosorbent assay and confirmation by detection of the virus RNA was proved to be the dominant strategy. The marginal cost-effectiveness ratios were for subjects under 40 and low-volume transfusion patients, 776,474 and 2,636,500 French Francs-1996 (about USD 111,000 and 376,650) per life-year gained, respectively. Sensitivity analysis showed that the marginal cost-effectiveness ratio was influenced by the prevalence and the survival rates. The lower marginal cost-effectiveness ratio was estimated at 690,221 French Francs-1996 per life-year gained. CONCLUSION: This study showed high costs and few life-years gained for the dominant strategy even for the more favourable risk group. New studies may be carried out for new screening and therapeutic strategies. PMID- 11766477 TI - Internal market systems in Sweden: seven years after the Stockholm model. AB - BACKGROUND: Sweden, like other European countries in the 1990s introduced internal market reforms in the delivery of health care. Specifically, in Stockholm county, the Stockholm model was introduced to strengthen the position of patients in their choice of care. Other reform measures introduced included the family doctor's legislation, care guarantee and the adel reform. This paper reports interviews with Swedish physicians, politicians and health economists seven years after the introduction of these reforms. The broader goals of this paper are to explore the extent to which these changes have overtime affected the views of physicians as they reflect on their working conditions and experiences with the use of the diagnostic-related groups (DRG) system. METHODS: Data was obtained from in-depth interviews of 15 primary care physicians, 4 heads of hospital departments (surgery), 5 county council members and 4 health economists (N = 28). A content analysis was performed on major themes on the interview transcripts. RESULTS: The majority of our respondents reported that the financial incentives introduced through performance-based reimbursements do exist in Stockholm county and that productivity and efficiency have increased over the period of investigation. Primary physicians voiced support for the privatization process in health care delivery. Most physicians reported that they were generally satisfied with their work. Over half of the general physicians complained about their working conditions but felt they have a unique way to play as 'gatekeepers' in the overall Swedish health care delivery system. CONCLUSION: Our findings suggest that physicians are generally satisfied with their working conditions. Over 90% of our respondents support the use of a diagnostic-related group. What is clear though is that the primary care physician's role due to its potential benefit as an agent of cost control is important, but it is not clear that the primary care physicians have made a major contribution to the Swedish health care delivery system as they should be. PMID- 11766478 TI - Governing people's lives. Strategies for improving the health of the nations in England, Denmark, Norway and Sweden. AB - Public health strategies reflect governments' wish to make people's lives longer and healthier. This can either be achieved by influencing the frames of people's lives and activities or the way they behave, i.e. to try to 'conduct their conduct'. In this paper the motivations for and methods of four national public health strategies are analysed. They are the English, the Norwegian, the Danish and the Swedish. Four questions are addressed: i) how is the governing activities aimed at improving the health of the population justified; ii) which issues are defined as problems; iii) which causes of the problems are identified; and iv) which governing techniques are suggested to solve the problems. The English and Danish programmes focus on mortality while the others give high priority to non lethal diseases and conditions. The Danish programme mainly aims at making people conduct themselves in a more healthy way, i.e. change their behaviour, often guided by health professionals. The Norwegian paper has empowerment as its central strategy. The strategy is based on the assumption that if people get more power over their own lives they will become more healthy and behave in a more healthy way. The Swedish emphasis is on changing people's living conditions and much less is said about the role of the individual. The English programme launches a national contract where individuals and authorities should work both to change people's behaviour and their living conditions. All strategies deal with the increasing social inequality in health, the English and Swedish strategies more than the others. There does not seem to be a specific Nordic model in this field of welfare state politics. PMID- 11766480 TI - Breastfeeding by objectives. AB - BACKGROUND: In many countries, the rates of breastfeeding fall far short of those recommended. National plans to promote breastfeeding are badly needed. We describe the results of a breastfeeding promotion programme planned by objectives and financial penalties in a small region of Italy. METHODS: This observational study was conducted in all the maternity hospitals and immunisation clinics of the six local health authorities of Friuli Venezia Giulia, in the northeast of Italy. The regional health authority included breastfeeding in its annual plans for 1998 and 1999, and asked local health authorities to develop local workplans and targets. A financial penalty was contemplated for local health authorities not achieving objectives and targets. The rates of exclusive, predominant and complementary breastfeeding were measured at birth and at 16-19 weeks of age. Data were collected, using standard definitions and methods, at discharge from hospitals and at the time of the second mandatory immunisation. RESULTS: All local health authorities and hospitals set up a breastfeeding reporting system in 1998 and defined breastfeeding promotion activities for 1999. The rate of exclusive breastfeeding at discharge and at 16-19 weeks increased significantly between 1998 and 1999, with a corresponding reduction of complementary breastfeeding. CONCLUSION: Financial penalties may contribute to the promotion of exclusive breastfeeding. PMID- 11766479 TI - East-west differences in reported preventive practices. A comparative study of six European areas of the WHO-CINDI programme. AB - BACKGROUND: Differences have been reported in life expectancy and mortality between Eastern and Western European countries. Also, disparities have been found among different European countries or populations concerning the implementation of preventive practices by health professionals. This study analysed the patterns of reported preventive practices in three Eastern European areas and three Western ones. METHODS: Health surveys were carried out in particular geographical area of six countries participating in the project (three Eastern European countries; Russia, Poland and Hungary and three Western European countries; Finland, Germany and Spain). All of them are partners in the WHO-CINDI (Countrywide Integration Non-communicable Diseases Intervention) Programme. Three preventive practices are analysed: reported blood pressure and blood cholesterol measurements and reported antismoking counseling during the last year. Data are presented separately for the general population and for people reporting specific chronic conditions (cardiovascular disease, respiratory disease and/or diabetes mellitus). RESULTS: Blood pressure measurement and antismoking counseling are more frequently reported to be carried out by primary health care physicians in the Eastern European areas while blood cholesterol measurement is more frequently reported in Western European countries. All these preventive activities are more frequently reported to be done among people with chronic conditions than in the population as a whole. CONCLUSIONS: Major differences have been found in reported preventive practices between Eastern and Western European countries. Great potential exists for chronic disease prevention among them. PMID- 11766481 TI - Impact of private funding on access to elective hospital treatment in the regions of England and Wales. National records survey. AB - BACKGROUND: The UK National Health Service aims to match access to health care to the level of need and to reduce inequalities in the health of sub-populations. One in ten persons have private medical insurance (PMI). This study describes the impact of private purchasing on access to hospital care in regions according to health need. METHOD: Details of admissions to NHS hospitals in one year and waiting times were obtained from the government's Hospital Episodes Statistics, and of patients in independent hospitals through weighted time samples of records. Data were combined into two groups, state funded and privately funded patients. The prevalence of limiting longstanding illness and the proportions of individuals covered by PMI in Wales and the eight English health regions were obtained from the General Household Survey. Correlation coefficients were calculated for inter-regional relationships between measures of need, provision of resources and levels of activity. RESULTS: Limiting, longstanding illness was significantly associated with NHS resource levels, NHS hospital activity, and total hospital activity, however funded; and inversely with PMI coverage, waiting times for NHS admission and levels of privately funded activity. Waiting times for admission were positively correlated with PMI coverage. CONCLUSIONS: Regionally, NHS resources and activity match need. Private hospital use complements lower levels of NHS service. Private consumption does not distort access according to need but in regions with lower levels of NHS activity those least deprived may make relatively more use of NHS hospitals, thus widening the health gap. Small area studies should explore this. PMID- 11766482 TI - Private practice in Slovenia after the health care reform. AB - BACKGROUND: Slovenia is one of the many post-socialist countries which started its reorientation of the health care system in the early 1990s. One of the aspects of the reform was the introduction of independent practice, which is performed either as a purely private practice on the basis of out of pocket payment or through contract with the National Health Insurance. A combination of both is also possible. In 1992 and 1993 the first physicians started to work in that way. The physicians that took this opportunity belonged to three main groups: dentists, primary health care physicians and secondary care specialists. The groups differ regarding their style of work and possibilities for running a profitable service. No studies have been done to evaluate the success of their decision. OBJECTIVES: The aim of the study was to evaluate the motives for leaving salaried posts, practice organization, perceived improvements and satisfaction with their choice of the practitioners who started to work independently in Slovenia in 1992 and 1993. METHODS: An anonymous questionnaire was sent to all self-employed physicians that started their independent practice in 1992 and 1993. A 54.5% response rate was achieved. The analysis of non responders has shown that they did not differ significantly according to sex, location of practice, speciality or method of payment, from the responders. RESULTS: The analysis shows that the reported reasons for choosing independent practice are not different across the groups. Possibility for greater income was not reported as a major reason for leaving public service. There are important differences in organization of work: general practitioners reported spending more time on patient contacts and administration than the other two groups; they also work exclusively for the National Health Insurance, which is not the case for the other two groups. The perceived areas of improvement differ substantially. Regardless, the overall satisfaction with their choice is high (over 90% would make the same decision again), the general practitioners are the most dissatisfied group. CONCLUSIONS: The analysis shows that self-employed physicians in Slovenia represent three different groups with different positions regarding how they earn their money. Their expectations have largely been met, since they claim that the doctor/patient relationship is better, as well as some conditions for the patients. A follow-up study that would take into account the long-term effects of privatization, and analysis of economic functioning and patient satisfaction would be necessary in order to verify these claims. PMID- 11766483 TI - Double exposure. The combined impact of domestic responsibilities and job strain on common symptoms in employed Swedish women. AB - BACKGROUND: This study investigated the influence of domestic responsibility and job strain, and especially simultaneous exposure to these factors (i.e. 'double exposure') on common physical and mental symptoms in Swedish women. METHODS: A questionnaire containing items on socio-economic factors, domestic responsibilities, and psychosocial working conditions was sent to a random population of women, 40 to 50 years of age, in a rural Swedish community. The response rate was 81.7% (397 women). Multiple logistic regression analyses were used to test for potential confounding factors and effect modification. Attributable risks were computed based on prevalence data. RESULTS: Women shouldering great domestic responsibility or who experienced job strain were at risk of a high level of common symptoms (OR 1.76; 1.04-2.97 and OR 3.48; 2.05 5.92, respectively). 'Double exposure' considerably increased the odds for common symptoms (OR 6.91; 2.58-18.48), with support for synergy noted. The population attributable risk (PAR) of great domestic responsibility was 10.0% and of job strain it was 26.7% in producing a high level of common symptoms. The corresponding figure for the population of women subjected to 'double exposure' was 11.8% and for the population of women subjected to either single or 'double exposure' the PAR was 30.3%. CONCLUSION: Heavy domestic responsibility and/or a job strain situation are factors that seem to make important contributions to the causes of a high level of common symptoms among salaried women 40 to 50 years of age. 'Double exposure' showed a particularly high risk because of synergy. PMID- 11766484 TI - The association between socio-economic status and chest pain, focusing on self rated health in a primary health care area of Sweden. AB - STUDY OBJECTIVE: The study objective was to determine, first, the association between men's and women's chest pain and their socio-economic status (occupation, smoking) and, secondly, the association between their socio-economic status and self-rated health, in a primary health care area. DESIGN AND SETTING: A population-based cross-sectional survey was made in a primary health care area of Sweden. Primarily based on occupation according to Swedish standards, 4,238 men and women were divided into two socio-economic groups; blue-collar and white collar workers. METHODS: Odds ratios with 95% CI were calculated by multivariate logistic regression, controlling for the variable age as confounding factor. Student's t-test was used to compare self-rated health, and the chi 2-test to determine any difference in smoking habits between the two groups. MAIN RESULTS: Both male and female blue-collar workers showed significantly more chest pain when excited than white-collar workers. In six of eight health indices, they also reported significantly worse self-rated health than the white-collar workers. CONCLUSIONS: These findings show that there are socio-economic inequalities in self-reported chest pain. Furthermore, socio-economic status has a major influence on self-rated health, acting across the working life of both sexes. PMID- 11766485 TI - HIV and hepatitis virus infections among injecting drug users in a medically controlled heroin prescription programme. AB - BACKGROUND: In Switzerland, 1,035 patients were accepted for admission to the medically controlled prescription of narcotics programme (PROVE) from 1 January 1994 until 31 December 1996. Heroin, methadone, and morphine were prescribed. This paper presents the prevalence and incidence of HIV and hepatitis B/C infections in the sociomedical context of the participants. METHODS: Admission criteria were a minimum age of 20 years, at least a two-year duration of daily heroin consumption, a negative outcome of at least two previous treatments, and documented social and health deficits as a consequence of their heroin dependence. The patients were examined at admission and every six months. A serological test was carried out at the same time for HIV and hepatitis B/C. RESULTS: Serological testing on admission could be performed in more than 80% of the entrants and documented a very high seroprevalence of antibodies against HBcore (73%) and HCV (82%). The prevalence of HIV and hepatitis B/C increased with duration of drug intake. In the follow-up analysis of seronegative individuals, a halving of the risk of viral hepatitis infection was shown when comparing the first six months with the period greater then six months after PROVE entry. CONCLUSION: The tests conducted showed high prevalence and incidence rates of HIV and hepatitis B/C among patients who had consumed intravenous drugs for years. The descriptive analysis in heroin-assisted treatment showed a reduction in infection risk for viral hepatitis corresponding to the lower risk behaviour of patients. PMID- 11766486 TI - Public health management of an outbreak of group C meningococcal disease in university campus residents. AB - BACKGROUND: Increasing numbers of outbreaks of Group C meningococcal disease in teenagers and young adults led to a new policy in the UK in 1999 of vaccinating all new college students. The largest of these outbreaks involved seven students in one university, six of whom were from one hall of residence, and two of whom died. METHODS: Control of the outbreak involved close medical surveillance of resident students, mass chemoprophylaxis and vaccination, and wide dissemination of daily information bulletins. Investigation of the epidemiology of the outbreak involved searching for the network of close contacts between cases, a prevalence survey of carriage of meningogocci and a case control study of risk factors for carriage. RESULTS: Clinical cases could be linked by a discrete network of social contacts within the halls of residence, but the Group C epidemic strain (2a P1.5) was not detected in 454 students (upper 95% confidence interval 0.7%). Carriage of any meningococcal strain (19%) was associated with patronage of the campus bar (OR = 3.0, 0.99-9.1). CONCLUSION: Important factors in the control of the outbreak were rapid institution of mass chemopropylaxis and immunisation of residents, and involvement of student organizations in the dissemination of information about the disease and its control. The role of campus bars in dissemination of the carriage of meningogocci deserves further investigation. PMID- 11766487 TI - Quality of life among children aged 2-17 years in the five Nordic countries. Comparison between 1984 and 1996. AB - BACKGROUND: The aim of the study was to analyse children's quality of life (QoL) in the five Nordic countries from 1984 to 1996, a period in which major economic recessions occurred. METHODS: The study design was cross-sectional based on a random sample of 3000 children in each country, aged 2 to 17 years, totalling 15,000 in 1984 and 15,000 in 1996. The data were collected by mailed questionnaires. QoL was analysed for three spheres of life: external, interpersonal, personal including both factual and perceived variables. The external sphere represented the socio-economic conditions for the child's family, the interpersonal sphere the structure and the function of the child's social networks and the personal sphere the psychological well-being of the child. RESULTS: The total QoL for Nordic children from 1984 to 1996 increased, but there were differences in the development of QoL between the countries. The objective QoL became better, at the same time the subjective QoL worsened, except in Denmark and Iceland. The external QoL became better, whereas the interpersonal QoL was nearly unchanged but there were differences in the development between countries. The personal QoL worsened slightly except for children in Iceland. The ranking between countries changed. Danish children had the highest subjective and Norwegian children the highest objective and external QoL. Swedish children had the highest personal QoL. Children 7-12 years had the highest QoL. Girls had a tendency to higher QoL in all ages. CONCLUSION: Nordic children still enjoy a high standard of living in spite of economic constraints, and the prerequisites for a high QoL are fulfilled. Further research is suggested for clarifying the complex background of these results. PMID- 11766488 TI - Effects of a population-based smoking cessation programme on smoking in pregnancy. AB - A controlled study was conducted to evaluate the effects of a low-intensity population-based smoking cessation programme in maternity care clinics. Quitting smoking during pregnancy was assessed by a self-administered questionnaire and verified by hair nicotine concentration. In the intervention area, 58/306 women (19.0%) reported quitting smoking during pregnancy whereas in the reference area the numbers were 22/152 (14.5%) (difference = 4.5%, 95% confidence interval: 2.6%-11.6%). The intervention group indicated that they received more information on adverse effects of smoking, studied the material more actively, and felt that material from maternity care influenced their smoking behaviour more than the reference group. PMID- 11766489 TI - The association between degree of nicotine dependence and other health behaviours. Findings from a German general population study. AB - BACKGROUND: To investigate the association between degree of nicotine dependence and unhealthy nutrition, lack of physical activity, and hazardous alcohol drinking. METHODS: Data with respect to cigarette and alcohol consumption, nutrition, and physical activity was collected in a representative general population sample (N = 4.075). RESULTS: Smokers with high compared to moderate and low degrees of nicotine dependence consume unhealthy foods more frequently, report less physical activity and more hazardous alcohol drinking. CONCLUSION: From a public health point of view, special secondary preventive interventions for smokers with high nicotine dependence and additional unhealthy behaviours are necessary. PMID- 11766490 TI - Translating evidence into practice. The case of influenza vaccination. AB - A problem common to all health care systems remains the translation of robust evidence into effective practice. Influenza vaccination has been reported to be an effective public health care intervention, but guidelines on coverage and subsequent uptake rates for vaccination across European countries vary substantially. One challenge therefore is to evaluate how effective different implementation mechanisms may be in improving overall vaccination rates for target populations across Europe. PMID- 11766491 TI - Different governments, different public health problems. PMID- 11766492 TI - Research in biomedicine. Is anyone representing/advocating the public interest? PMID- 11766493 TI - The humble defence. PMID- 11766495 TI - Supplement on smoking cessation. PMID- 11766494 TI - Supplement on smoking cessation. PMID- 11766496 TI - [Vascular surgeon is on the look-out for a like-minded internist]. PMID- 11766497 TI - [Should patients with small cell lung cancer be offered prophylactic cranial irradiation?]. PMID- 11766498 TI - [Lipid lowering treatment of patients with atherosclerotic disease of the lower extremities]. AB - Patients with critical peripheral ischaemia have a significant mortality rate of up to 50% within 4-5 years of surgical vascular reconstruction. This poor survival rate is due to concomitant coronary and cerebrovascular atherosclerotic disease. Large randomised trials have shown that dyslipidaemia is easily modifiable in patients both with and without established coronary artery disease, with significant reductions in cardiovascular morbidity and mortality. Although none of these trials directly measured peripheral vascular status, there is every indication that conclusions submitted for patients with ischaemic heart disease can be translated to patients with peripheral arterial disease (PAD). The object of this review was therefore to divulge the current evidence available, which supports active treatment of dyslipidaemia in patients with PAD. PMID- 11766499 TI - [Diagnostic imaging of inflammatory rheumatic joint diseases. Part I: peripheral joints]. AB - The options for peripheral joint imaging in inflammatory joint diseases have increased markedly over the last few years. High-frequency ultrasonography and magnetic resonance imaging in particular appear to have a large potential in the diagnosis, monitoring, and prognostication of these diseases. However, the new methods have still to be fully validated. In clinical practice, it is essential to use a validated method, generally conventional radiography, as the first "basic" imaging modality. As newer methods may provide significant additional information, it is also very important that the value of these is evaluated in scientific studies. This article reviews current knowledge of conventional radiography, computer tomography, ultrasonography, and magnetic resonance imaging in the assessment of peripheral joints in inflammatory joint diseases. PMID- 11766500 TI - [Diagnostic imaging of inflammatory rheumatic joint diseases. Part II: techniques and axial joints]. AB - Imaging of inflammatory disorders of the spine and sacro-iliac joints is important for the diagnosis, prognosis, and evaluation of therapy. Conventional radiography still constitutes the basic imaging modality, but supplementary computed tomography (CT) and especially magnetic resonance imaging (MR-scanning) may provide additional important information. The radiation dose by CT must be taken into account. It is therefore expected that MR-scanning, which is without known risks, will increasingly become the method of choice when the information obtained by conventional radiography is inadequate. PMID- 11766501 TI - [Complications of transligamental knee arthroscopy. The frequency of pain and ultrasonographic changes in the inferior patellar tendon]. AB - INTRODUCTION: We wanted to investigate whether the transtendineous portal for arthroscopy was causing damage to the patellar tendon (PT). We also wanted to assess postoperative complaints related to the patellar tendon. METHODS: Out of 59 consecutive patients, who had neither anterior knee pain nor ultrasonographic changes in the tendon, and who had a planned transtendineous arthroscopy of the knee because of a suspected meniscal lesion or osteoarthritis, 36 patients were given both a clinical examination and ultrasonography of the PT before surgery and at two and six months. RESULTS: At the six months follow-up, 20 patients had tenderness of the PT, which was fewer than at the two-month follow-up. Ten patients had signs of granuloma formation of the patellar tendon and four had signs of perifibrosis/peritendinitis on ultrasonography. There was no statistical correlation between tenderness of the patellar tendon and granuloma formation (p = 0.48, Fisher's exact test) or perifibrosis/peritendinitis (p = 0.78, Fisher's exact test). DISCUSSION: More than 25% of the patients showed granuloma formation on ultrasonography and more than 50% had complaints from the patellar tendon, but both the symptoms and the complaints seemed to decline over time. The consequences of the postoperative changes in the patellar tendon six months postoperatively are uncertain, as there was no statistical correlation between tenderness of the PT and the findings at ultrasonography. Further studies are recommended to investigate the changes in the PT when this method is used. PMID- 11766502 TI - [Age distribution of hospital autopsies 1977-1996. The relative frequency of autopsies on younger people has increased since the 1990 amendment]. AB - INTRODUCTION: Since the new law on autopsies was passed in 1990, the frequency of autopsy has fallen. We have carried out an analysis to illustrate the conditions/proportions for various age groups before and after the law came into force. METHOD: All the figures for deaths and autopsies during the period of 1977 1996 were reviewed. This includes the figures from the Danish Board of National Health and from the Department of Pathology at Rigshospitalet, Copenhagen. The frequency of autopsy was calculated for all groups, both before and after the amendment, and the results are discussed. RESULTS: The figures showed not only a significant decrease in the frequency of autopsy in almost all groups, but also a considerable decrease in the groups of the elderly as compared to the younger groups. DISCUSSION: The frequency of autopsy decreased during the period of 1977 1996. The most significant fall was seen around 1990, both in the general figures registered in connection with the cause of death and in the figures from the Department of Pathology at Rigshospitalet, Copenhagen. We also found that the decrease in the frequency of autopsies was greater in the groups of the elderly, when different age groups were examined. The percentage of autopsies performed on younger people has increased since the 1990 amendment. PMID- 11766503 TI - [Treatment of tibial shaft fractures in Denmark]. AB - INTRODUCTION: Only a few randomised studies have been published on the treatment of tibial shaft fractures. We therefore expected a great diversity in the choice of treatment methods in Denmark. In order to analyse this, we carried out a questionnaire investigation. MATERIAL AND METHODS: In autumn 1997, a questionnaire was sent to all departments in Denmark where tibial fractures are treated. The fractures were classified according to stability, amount of energy, and the degree of soft tissue injury. RESULTS: Ninety-three per cent of the departments answered the questionnaire. We present here the results with respect to the use of antibiotics, thrombosis prophylaxis, invasive pressure measuring, and the choice of treatment: conservative or operative methods and techniques. DISCUSSION: As expected, we found a significant variation in the choice of treatment of tibial shaft fractures in Denmark. This is consistent with the recommendations in the literature, which vary somewhat and are mostly based on non-randomised studies. PMID- 11766504 TI - [Hydroxyurea-induced leg ulcers in patients with chronic myeloproliferative disorders]. AB - INTRODUCTION: Hydroxyurea (HU) is usually a well-tolerated antineoplastic agent, which is commonly used in the treatment of myeloproliferative disorders. Dermatological abnormalities are often seen in patients receiving long-term HU therapy. Leg ulcers have been reported occasionally. MATERIAL AND METHODS: We carried out a prospective and descriptive study of patients who developed leg ulcers while receiving HU therapy. RESULTS: Between 1.1.1997 and 1.2.1998, chronic cutaneous leg ulcers were found in five out of a total of 28 patients treated with HU. The average age was 76 years (64-87 years). Two patients had chronic myelogenous leukaemia in a non-accelerated phase, two polycytaemia vera, and one essential thrombocytosis. The average duration of HU therapy was 30 months (10-55 months) before ulcerations appeared. These were typically located on the malleolar and/or perimalleolar area, and were very painful. HU therapy was discontinued and replaced by busulphan or anagrelide. Within 1.5-11 months of discontinuation of the treatment, the wounds had healed or improved. DISCUSSION: We found a surprisingly high number of cutaneous leg ulcers in patients on HU therapy for chronic myeloproliferative disorders. We believe this disabling complication should be given greater attention and recommend that it is included in the description of the side effects of the drug. PMID- 11766505 TI - [Accelerated course in hip arthroplasty]. AB - INTRODUCTION: The aim of the study was to assess the results of a well-defined rehabilitation programme after hip arthroplasty. METHODS: The effects of a revised, optimised, perioperative care programme with continuous epidural analgesia, oral nutrition, and physiotherapy were assessed in 60 patients before intervention and 60 patients after intervention. RESULTS: The hospital stay was reduced from nine to six days (p < 0.01), there were fewer complications and less need for rehabilitation after discharge (p < 0.05) in the intervention group. CONCLUSION: A clinical programme focusing on pain relief, oral nutrition, and rehabilitation may reduce the stay in hospital and improve recovery after hip arthroplasty. PMID- 11766506 TI - [Hurricane-related orthopedic surgical admissions to an emergency department in December 1999]. AB - INTRODUCTION: On 3 December, 1999, at 15.00 pm, hurricane Adam struck Esbjerg (Denmark). Wind velocity exceeded 33 m/s, the strongest hurricane ever recorded in Denmark during the last century. This article describes and analyses the orthopaedic impact of the hurricane on a local hospital in Esbjerg. MATERIALS AND METHODS: We examined retrospectively all the patients treated at the Emergency Department from 3 pm on 3 December and for the following 24 hours. For comparison, we used the records of all patients treated at the Emergency Department in the same time interval on the first three Fridays in December from 1994 to 1998. RESULTS: No hurricane-associated deaths were recorded, but the number of patients treated on 3 December was significantly higher than that recorded in the period 1994-1998 (159 versus 74, p < 0.001). The main diagnosis was similar to that of the previous years, but more people sought treatment at the Emergency Department. Sixty-eight percent of the recorded injuries were injuries to the upper and lower extremities and 22% to the head and neck. DISCUSSION: Hurricanes can lead to substantial morbidity and mortality. Early warning is the most effective way of reducing death and injury. People should seek cover and follow the instructions given by the news media. Educational programmes for the medical staff of the Emergency Department should be made available. PMID- 11766508 TI - [Discoid lateral meniscus. The importance of MRI scanning for the diagnosis]. AB - This article reports a case of a complete discoid lateral meniscus with an anteriomedial cleavage tear in a 4-year-old boy diagnosed by MRI. The patient underwent arthroscopy with findings of a torn complete discoid lateral meniscus. As the peripheral rim of the meniscus was stable, a partial meniscectomy with reshaping was done. At follow-up two years postoperatively, the patient had recovered uneventfully. PMID- 11766507 TI - [Spontaneous dissection of the left main coronary arteries in three women]. AB - Spontaneous dissection of the coronary artery is a rare cause of sudden death and myocardial infarction. We report three cases in women aged 32, 38, and 55 years. One patient was one week post partum. In one case all three coronary arteries were involved. Two patients underwent coronary artery bypass grafting and one died of acute heart failure. The epidemiology, aetiology, and clinical manifestations are briefly described. We suggest that coronary angiography should be considered in young women with acute myocardial infarction and few risk factors of atherosclerosis. PMID- 11766509 TI - [Picture of the month: cold agglutinin syndrome and Raynaud's phenomenon]. PMID- 11766510 TI - [Insulin treatment of critically ill patients]. PMID- 11766511 TI - [The radio doctor rides old-fashioned waves]. PMID- 11766512 TI - Angina treatments. What's best for you? PMID- 11766514 TI - Camera in a pill is new way to capture digestive tract images. PMID- 11766513 TI - Health tips. Preventing carbon monoxide poisoning. PMID- 11766515 TI - Exercise may reduce risk of pancreatic cancer. PMID- 11766516 TI - Statins. Cholesterol-lowering and more in a pill. PMID- 11766517 TI - Cellulitis. A spreading infection. PMID- 11766518 TI - Diabetic retinopathy. Early treatment can thwart vision loss. PMID- 11766519 TI - What are the most effective teeth-bleaching procedures? Are they safe? PMID- 11766520 TI - I used some of my daughter's headache medication and had complications. I'm sure I've taken this before. Why would I react now? PMID- 11766522 TI - Prenatal development of the muscles in the floor of the mouth in human embryos and fetuses from 6.9 to 76 mm CRL. AB - The development of the muscles in the floor of the mouth is described in 10 human embryos and fetuses ranging from 6.9 to 76 mm CRL by means of computer-aided graphical 3D-reconstructions. All primordia of the muscles in the floor of the mouth could be identified from the 15.6 mm CRL stage on. The proportions and insertion lines of the early muscles were found to be different from adult anatomy. Each muscle first inserted in the medial surface of Meckels cartilage, but during the developmental period between 19 and 68 mm CRL the insertion lines were gradually transposed to the bony ridges of the mandible which progrediently embraced Meckels cartilage. The fibers of the mylohyoid muscles left the anterior region near the symphysis mentalis free during all stages of this study. The digastric muscle revealed only one belly with a constriction of its continuous fibers where it passed the hyoid bone primordium. There was no attachment of digastric muscle fibers to the hyoid; only geniohyoid and mylohyoid fibers. Geniohyoid and genioglossus muscles basically correspond to their definite arrangement, but they underwent proportional changes. Individual specimens embodied irregularities such as accessory geniohyoid and hyoid portions and muscle fibers separate from the mylohyoide muscle. PMID- 11766521 TI - [The reelin signal pathway and the development of cell- and filament-layers in cattle brain]. PMID- 11766523 TI - [The extralobar sequestration of the fetal lung]. AB - The extralobar sequestration is a rare pulmonary malformation. An accurate antenatal evaluation is required for a timely therapy and subsequently a good outcome. Here an unusual case of extralobar pulmonary sequestration in a male human fetus is reported. Antenatal ultrasound at 28th week of gestation has revealed a fetal hydrothorax in coexistence with pulmonary hypoplasia and an isolated pulmonary structure. Authors summarise their postnatal findings with special reference to the pathogenesis of an accessory lung. The aim of this report is to define the association of clinical, gross, and histological features of this rare congential malformation in order to improve the antenatal diagnosis. This case indicates that an extralobar pulmonary sequester is not connected to the tracheobronchial tree, and that the arterial as well as the venous blood supply is realised by aberrant systemic vessels. Moreover, histologically revealed dilatations of the normally differentiated terminal airways within the sequester suggest that hyperechogenity can not be a reliable diagnostic criterion. For the accurate assessment of a pulmonary sequestration a detailed antenatal evaluation of both, the arterial and the venous blood supply is essential. PMID- 11766524 TI - Morphological characteristics of styloid process evaluated by computerized axial tomography. AB - Morphological characteristics of styloid process and ossified stylohyoid ligament and their overall relationships to age and sex were studied by using computerized axial tomography images. The styloid process and ossified stylohyoid ligaments were classified into seven groups according to their shapes and lengths. The styloid process of a length of 25-40 mm, was the most frequently encountered. The elongated styloid process was mostly seen in males. There was no overall correlation between the types of SP and sex. The progressive increase in length with age was not seen in our study. PMID- 11766525 TI - Relative weights of the human carpal bones: biological and functional interests. AB - The relative carpal weights (Weight of each of the eight carpal bones/Weight of the complete carpus x 100) were studied in a series of 95 complete human adult carpi (dried bones). The greatest was the capitatum (19.92%; mean rank 1.16) and the smallest the pisiform (4.43%; mean rank 8.00). The scaphoideum and the hamatum presented very near values (17.19 and 15.81%; mean ranks 2.34 and 2.74), as did the lunatum and trapezium (12.56 and 12.52%; mean ranks 4.41 and 4.48), and the triquetrum and trapezoideum (9.21 and 8.36%; mean ranks 6.19 and 6.68). Within the proximal row, a regular radio-ulnar decrease was observed from the scaphoideum (39.58%) to the pisiform (10.20%). Within the distal row, a marked break existed between the trapezoideum (14.77%) and the capitatum (35.19%); the capitato-hamatal element represented 63.11% of the distal row. The distal row (mean 56.61%) was always a little heavier than the proximal row (mean 43.39%), resulting in a mean proximo-distal weight ratio of 0.77. A radio-ulnar decrease in the relative weights was observed from the radial to the ulnar carpal columns. The determination of the relative carpal weights is simple, reproducible, non invasive, rapid, and inexpensive, and can be considered an interesting and valuable approach to the estimation of the relative carpal volumes. Relative carpal weights reveal the intrinsic proportions of the carpus and are the reflection of biological, functional and evolutionary constraints. Interesting relations appear with carpal growth and ossification, with functional characteristics, and with evolutionary processes. PMID- 11766526 TI - Anatomical variations in the human testicular blood vessels. AB - The testis is an important organ upon which the survival of the human species depends. The testicular arteries and veins play major roles in the thermo regulation that is essential for the efficient functioning of this organ. However, very little is found in the literature about the veins and their anatomical variations. Therefore the testicular veins and arteries in 150 dissection room cadavers at the University of the Witwatersrand, Johannesburg and University of Zimbabwe, Harare were examined for anatomical variations from the usual descriptions in textbooks of Anatomy. Variations were found more frequently in the testicular veins than in the accompanying arteries. The variations, which were more common on the left side, were seen in 32 (21.3%) of the cadavers. In 6 (18.8%) of these cases, the variations were present bilaterally. The veins were either completely or partially duplicated, with or without beading. The duplicated veins terminated in the corresponding renal veins either separately or after combining into one vein. In two cases, the right testicular vein terminated in the right renal vein, rather than in the inferior vena cava. Anatomical variations of the testicular artery were present in 4.7% of cases and were associated with their origin, which were either from unusually high levels of the abdominal aorta or from the renal artery. PMID- 11766527 TI - A mathematical model of the ascending colon of the horse. AB - In this study we present a geometric model of the ascending colon of the horse, especially the left ventral colon and the right ventral colon, the left dorsal colon and the right dorsal colon and the pelvic flexure. We also present a mathematical model of the cross sections of these ascending colon parts with the exceptions of the pelvic flexure. We show that these cross-sections correspond to the closed algebraic curves known as epitrochoid. PMID- 11766528 TI - A geometric description of the ascending colon of some domestic animals. AB - In this study, a geometric recognition of the ascending colons of some domestic animals such as pig, ruminants (only the ansa spiralis coli) and dog is presented. The ascending colon of these animals can be considered a tubular shape along a special curve. PMID- 11766529 TI - Angiomorphology of the pigmented Bomirski melanoma growing in hamster eye. AB - An melanotic line of Bomirski Hamster Melanoma (BHM Ma) was implanted into the anterior chamber of the hamster eye and the ensuring vascular system was studied using scanning electron microscopy (SEM) of vascular corrosion casts. The tumor vasculature, induced mainly from the host iris vessels, showed generally disorganized and irregular patterns. Tortuous tumor capillaries of uneven contour with local dilatations and constrictions were drained by markedly dilated, thin walled, venous vessels connected with the eye veins. Vascular sprouting and, less frequently, intussusceptive formation of new vessels were observed at the periphery and also within the tumor mass. The presence of numerous nodular outgrowths, varying in size, on the surface of dilated venules and venous vessels represent morphological evidence for continuous remodeling of the tumor vasculature. The observed features of the vascular system seem to provide a pathway for further tumor expansion. Our study showed that BHM Ma line, originating from an aggressive skin melanotic melanoma, implanted to the eye anterior chamber gave rise to rapidly growing tumors with the capability of inducing abundant vasculature which allows metastasis to the lungs, kidneys and regional lymph-nodes. PMID- 11766530 TI - Prostaglandin F2 alpha can modulate the growth and the differentiation of bovine corneal epithelial cells cultured in vitro. AB - The effects of PGF2 alpha on the growth, morphology, morphometry and keratinization pattern of bovine corneal epithelial cells cultured in vitro were studied. The cells were grown with a basal medium or, in the presence of keratocytes and/or their products, using a keratocyte-conditioning medium. Cell growth was evaluated by MTT assay. Daily treatments with exogenous PGF2 alpha at concentrations equal to or lower than 10(-6) M induced significant increases in cell proliferation when the epithelial cells were cultured on a keratocyte feeder layer or with the conditioning medium. No variations were observed in cultures grown with the basal medium. 10(-5) M PGF2 alpha induced a decrease in cell growth under all culturing conditions. PGF2 alpha did not affect cell morphology and modified only nuclear dimensions among the cells grown under different culturing conditions. No variations of any parameters were observed between cells cultured on feeder-layer, with conditioning or basal medium and the corresponding cultures supplemented with the autacoid. Moreover, PGF2 alpha induced only the disappearance of 43 kDa keratin in cells grown on basal medium, while the keratin pattern of epithelial cells cultured on feeder-layer or with the conditioning medium was not modified by the autacoid. From these data we can suppose that a cooperation could exist between PGF2 alpha and fibroblasts and their products for the modulation of cell growth. Finally, it was observed that the autacoid had no effect on cell morphology and morphometry, except for nuclear dimensions, despite the presence of other prostaglandins, such as PGE2. PMID- 11766531 TI - Weekly quizzes in extended-matching format as a means of monitoring students' progress in gross anatomy. AB - We compared weekly quizzes in extended-matching format with multiple-choice questions and oral examinations as means of monitoring students' progress in gross anatomy. Students' performance on 19 weekly oral examinations or 10 question quizzes based on extended-matching or multiple-choice formats were correlated with their success on 3 interim examinations and the final comprehensive examination. The Kuder-Richardson formula 20, an estimate of precision of the test, was 0.64 for extended-matching quizzes. Students' performance on interim examinations did not differ significantly. There was a significant correlation between students' mean scores on weekly quizzes and mean scores on interim examinations in both the extended-matching (r = 0.516) and multiple-choice group (r = 0.823). The mean grades (ranging from 2 to 5) on the final exam, based on understanding of anatomical concepts and their application in clinical practice, were significantly higher in extended-matching group (4.8) than in the multiple-choice (4.1) and orally examined groups (3.9) (p < 0.05). We conclude that extended-matching quizzes were at least as effective as multiple choice quizzes and oral examinations and may be better for acquiring synthetic understanding of anatomical concepts especially in combination with other means of knowledge assessment. We recommend them as a reliable and objective means of monitoring students' performance during a gross anatomy course. PMID- 11766533 TI - [Introduction series, 'Modern biotechnology: blessing or curse?']. PMID- 11766532 TI - [Malignant lymphoma in the horse: an atypical clinical manifestation]. AB - In this case report we describe an atypical clinical manifestation of malignant lymphoma in a horse. The most obvious clinical symptoms were hyperaemic mucosae and skin lesions. The skin and mucosal lesions appeared to be caused by a leukemic form of malignant lymphoma. The lymphocytosis consisted mainly of different populations of T-lymphocytes. Histopathology and immunohistochemistry identified the malignant lymphoma as a T-cell rich B-cell lymphoma. PMID- 11766534 TI - [DNA: what does it do, and what do we do with it?]. AB - We present a bird's-eye view of the fundamentals and applications of the DNA technology. DNA is the carrier of genetic information. Separate pieces of DNA can be isolated in two different ways: cloning or via the polymerase chain reaction. Analysis of DNA has already found several applications in medical diagnosis and criminal investigations. Modification of DNA from lower organisms in order to produce proteins is now generally accepted. Genetic modification of plants and animals is promising, but is also the subject to a public and political debate. Gene therapy is a promise of the future. Analysis as well as modification of DNA has ethical consequences and both require an effective legislation. PMID- 11766535 TI - [Jos Goebbels back after spending 3 years in New Zealand. In search of professional integrity for the veterinarian]. PMID- 11766536 TI - [Stray animals or lost bills?]. PMID- 11766537 TI - [Overturning of regulation for human, animal and society]. PMID- 11766538 TI - [Preventive vaccination against foot and mouth disease not a realistic scenario?]. PMID- 11766539 TI - [contra indication of corticosteroids]. PMID- 11766541 TI - [Spontaneous bacterial peritonitis in hepatic cirrhosis with ascites: incidence, bacteriology and mortality in Uruguay]. AB - Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites. In order to analyze the incidence, bacteriology and in-hospital mortality, we studied 64 consecutive patients with cirrhosis and ascites (47 males, 17 females average age 59 years) hospitalized in a general adults 3rd level hospital (Pasteur hospital, Montevideo, Uruguay), between September 1998 and May 2000. The diagnostic criteria was more than 250 polymorphonuclear cells/cu.mm. in ascitic fluid and/or a positive culture. We found 17 SBP in 17 patients (10 males 24-81 years) which means an incidence of 26.56%. 15 alcoholic cirrhosis and 2 autoimmune disease. 12% (2/17) were asymptomatic; 8/17 were SBP culture positive (5 E. Coli, 2 St. Pneumoniae, 1 Klebsiella sp.), and 9 were culture negative. The mortality rate associated with SBP was 47% (8/17), greater than the cirrhotic group without SBP (12.7% p < 0.01). PMID- 11766542 TI - [Diagnostic value of defecography]. AB - The aim of this study was to assess the importance of defecatography in the diagnosis of lower chronic constipation (4) or rectal type (12), principally in those patients on whom other diagnostic methods had not produced supportive data. Over a 64 month period, 65 patients who had consulted because of chronic constipation, were studied; they were suffering from low bowel symptoms like difficulty in the evacuation of the rectum. The average age was 48 and mostly female. All of them were asked to prepare the same mixture for the defecatory study, using the same type of contrast material and study technique. In most of the cases correlated functional elements were found, while very few cases resulting from just organic causes were found, and only one without functional or organic reason was found. Our results were as follows. 1) Insufficient laxity of the pubo-rectal beam related to forward or backward rectocele or lowering of the increased pelvic floor, a fact that was found in 19 patients (29.23%). 2) Inadequate laxity of the pubo rectal beam in 12 patients (18.46%). 3) Paradoxical contraction of the pubo rectal beam related to forward rectocele or lowering of the increased pelvic floor, in 11 patients (16.92%). 4) Lowering of the increased pelvic floor, related to forward or backward rectocele in 8 patients (12.30%). 5) Paradoxical contraction of the pubo rectal beam in 7 patients (10.76%). 6) Forward or backward rectocele in 3 patients (4.61%). 7) Lowering of the increased pelvic floor in 2 patients (3.07%). 8) Rectal intususception in 1 patient (1.53%). 9) Average study in 1 patient (1.53%). Therefore, the defecatography is a very useful method of study to appraise constipation with anorectoperineal symptoms, as it allows us to diagnose organic and functional problems in the area (6). Likewise, the importance of pre and post surgical tests, both therapeutic and reconstructive must be underlined. PMID- 11766543 TI - [Pseudo acute pancreatitis: a syndrome mimicked by a multiple parasitic duodenitis. Analysis of 7 case]. AB - INTRODUCTION: The aim of this presentation was to analyze a clinical syndrome characterized by repeated episodes of upper abdominal pain, markedly increased levels of both total amylase and lipase, but with normal values of pancreatic isoamylase. Besides, with the lack of morphologic changes of the pancreatic gland, either by ultrasound, abdominal tomography, or Nuclear Magnetic Resonance. MATERIAL, METHODS AND RESULTS: Five female and two male patients, with an average age of 51 +/- 3 were studied. All had been diagnosed as having acute edematous pancreatitis (ranson score < 3). Laboratory tests had disclosed eosinophilia (5 30%); total amylasemia (1547 +/- 398 UA/l); lipasemia (857 +/- 499 UBL/L); normal pancreatic isoamylase (72 +/- 18 UA/L). Upper endoscopy showed nonspecific signs of duodenitis sometimes with duodenal erosions. Collection studies, pre and post Sorbitol, disclosed an unexpected multiple parasitic infestation, e.g.: giardias, ascaris, amoeba, hymenolepis nana. This finding was always suggestively associated with abundant sludge (bilirrubinate cholesterol and oxalate crystals). All patients, after having been submitted to the appropriate antiparasitic medication, were rapidly relieved of their symptoms and remained free of episodes of abdominal pain. CONCLUSIONS: When the fact that all our patients had normal pancreatic isoamylase levels and lack of any morphologic distortion of the pancreatic parenchyma is associated to the notion that total amylase and lipase may have as a source the gastrointestinal mucosa, it appears as a logical inference that the clinical syndrome here discussed is indeed primarily a reflection of an extrapancreatic disease, essentially of parasitic duodenitis. PMID- 11766544 TI - [Precut Vater's papilla. Prospective evaluation of frequency of use, effectiveness, complication and mortality. Cooperative study in the northwest of the province of Buenos Aires]. AB - INTRODUCTION: Precut papillotomy, has been considered a potentially dangerous procedure. In spite of this, numerous national and foreign referral centers have reported good results with the use of this technique that increases the cannulation rate and permits additional therapeutic procedures. OBJECTIVES: We evaluated the procedure in terms of frequency of use, effectiveness, complications and mortality. PATIENT AND METHODS: Between January 1, 1996 and December 31, 1999, 419 ERCP were performed in our centers. We used precut papillotomy in 51 patients. Inclusion criteria for precut papillotomy protocol were: 1 precut papillotomy indication. 1-1 failure to cannulate the papilla, 1-2 appropriate indication, 1-3 Expert endoscopist, 2 complete follow up, 3 informed consent. The experimental design of the study was prospective. When the patients entered into the protocol, they underwent a needle-knife sphincterotomy according to Huibregise's technique. The follow up was done during 30 days, with a clinical examination, laboratory test and ultrasonography all of them weekly, to determine the possible complications according to Cotton's criteria and the mortality. RESULTS: 4-1) Precut frequency: 51 patients (pts.) (12.1%). 4-2) Follow up: 49 pts. (96.1%) fulfilled the weekly controls; 2 pts. (3.9%) did not come for the controls. 4-3) Sex and Age: Women 29 pts. (56.9%). Age 62.5 +/- 1.74 years. Men: 22 pts. (43.1%) Age +/- 3.35 years. 4-4) INDICATIONS: Jaundice, diagnosis and treatment: 44 pts. (86.3%), post-cholecystectomy pain; 4 pts. (7.8%), and idiopathic abdominal pain: 3 pts. (5.9%). 4-5) Effectiveness: First attempt 35 pts. (71.4%), second attempt: 10 pts (20.4%). Definite effectiveness: 45 pts. (98.1%), failure: 4 pts. (8.1%). 4-6) Complementary treatment: in 43 pts. we performed the following procedures: papillotomy and stone extraction: 26 pts. (53%), papillotomy and prosthesis: 9 pts. (18.4%), Prosthesis: 8 pts. (16.3%, only pre-cut papillotomy: 6 pts. (12.2%). 4-7 Final diagnoses: Coledocholithiasis 41 pts. (83.6%); Malignant obstruction of biliary duct: 4 pts. (8.2%), Pancreatic Cancer: 1 pts. (2%); Ampullary Cancer 1 pts. (2%). Oddi sphyncter dysfunction: 1 pts. (2%). 4-8. COMPLICATIONS: Total 9 pts. (18.4%). mild Haemorrhage: 7 pts. (14.4%). Acute pancreatitis: 2 pts. (4%), mild: 1 pts. (2%), severe: 1 pts. (2%) 4-9-Mortality: not recorded. CONCLUSIONS: 5-1 Precut papillotomy is used by us with the same frequency native authors use it, but less than foreign authors. 5-2 Age, sex, indications, complementary treatment and final diagnoses are similar to those repo. 5-3 reported by other authors. 5-3- High rate of follow up. 5-4- High percentage of effectiveness which coincide with consulted studies. Precut papillotomy was the only therapy in 12.2% of the cases. 5-5 Low percentage of complications and, when present, of minor importance coinciding with other authors. 5-6 No mortality. 5-7 In our experience, precut papillotomy was a safe and effective technique to cannulate the papilla. PMID- 11766545 TI - Choledochal semi volvulus with jaundice due to hiatal hernia. Initial percutaneous management. AB - Large diaphragmatic hernias are rare causes of common bile duct strictures. We report a case of mixed (slide and paraesophageal) hiatal hernia with jaundice due to choledochal dislodgment and torsion. The first time we named this entity choledochal semi volvulus. Its pathophysiology is analyzed and we remark the wise and accurate percutaneous management as diagnostic and initial therapeutic resources. PMID- 11766546 TI - [Cystic duplication of the esophagus]. AB - Duplication is defined as the presence of a complete or partial double structure, with a variable length. In esophagus, duplications, diverticuli and cysts might be manifestations of the same embriologic defect. The most common is the Cystic Duplication of the esophagus (CDE), which represents the esophageal duplication, either spherical or tubular, with squamous or columnar epithelium, and a double muscular layer. CLINICAL CASE: male, 38 years old with no previous relevant data, and sudden, complete and persistent post ingestion aphagia, intense presternal pain, and a 12 Kg. weight loss in 15 days. Endoscopy showed unsurpassable stenosis of the lower third of the esophagus, with normal mucosa. Total esophagectomy and replacement with a gastric tube, was performed. He had a good postoperative course. PATHOLOGY: A total esophagectomy open specimen showing a cystic structure at the posterior wall was submitted, which showed a thick, muscular-like wall and hemorrhagic internal surface. Microscopically it had a pseudostratified columnar, ciliated epithelium, alternating with sloughed hemorrhagic areas, fibrosis and stromal siderophagi Leiomuscular double-layered wall. CDE is very infrequent, and is the second most frequent after leiomiomas as a benign esophageal mass. From 10 to 15% of all digestive duplications take place at the esophagus. There are different theories to explain its origin. Differential diagnosis must be made mainly with brochogenic cyst, generally anterior and with cartilage. Treatment is surgical. PMID- 11766547 TI - [The patient with irritable bowel syndrome. A difficult patient?]. AB - The treatment of patients with Irritable Bowel Syndrome has not been very successful because of the number of variations that are associated with the illness. Some of them are: Depression and Anxiety, intensity of the symptoms and colonic hypersensitivity, all this, added to the unknown etiology of the illness. This review expects to bring a global vision of the difficulty that has existed for Medicine or psychology to bring the best treatment to these patients. Diverse investigations had obtained successful results with different psychotherapeutic approaches (Hypnotherapy, Psychoanalysis, cognitive therapy, multicomponent therapy, etc.). Nevertheless these present methodological errors that put in doubt those results. It is thought that interdisciplinary treatment would be a good option for these patients. PMID- 11766548 TI - [Spontaneous bacterial peritonitis. Advances in the recognition of prognostic factors and in its treatment]. PMID- 11766549 TI - [Papillary pre cut. Is it a tool or a weapon?]. PMID- 11766550 TI - Measuring telomerase activity for the early detection of cancer. AB - Telomeres are the terminal portions of chromosomes and consist of the repeated nucleotide sequence TTAGGG. Chromosomes lose a small amount of telomeric deoxyribonucleic acid (DNA) after each cell replication. A hypothetical function of telomeric DNA is to allow for a finite number of cell divisions without loss of functional genes. A second proposed function of telomeric DNA is to prevent undesirable interactions between chromosomal ends and cellular repair enzymes. In cells that maintain a proliferative capacity, such as stem cells and cancer cells, telomere length is maintained by the reverse transcriptase, telomerase. Virtually every major human malignancy has been evaluated for telomerase activity and approximately 80% to 90% have demonstrated the presence of telomerase. In this article we review the current assays available for telomerase detection and discuss their relative strengths and limitations. PMID- 11766551 TI - Severe hepatitis due to HBV-HDV coinfection. AB - Quadruple hepatic infections are not uncommon in human immunodeficiency virus (HIV) infected patients. Hepatotropic viruses behave differently in immunocompromised patients resulting in varied clinical and serological outcomes. Delta hepatitis, an important cause of acute hepatitis in intravenous drug abusers (IVDAs) and HIV-infected patients, can present as coinfection or superinfection clinically, which influences the prognosis. Prevention of hepatitis D virus (HDV) coinfection is possible with hepatitis B virus (HBV) vaccination. No definitive medical treatment for HDV infection is known to be successful. Interestingly, liver transplantation carries a higher success rate in HDV/HBV infection then in HBV infection alone. PMID- 11766552 TI - Acute unilateral pulmonary edema from dietary salt and water load: a case report and review of the literature. PMID- 11766553 TI - Growing public scrutiny of FDA clinical trials: ethical and regulatory compliance to avoid "uninformed consent" and financial conflicts of interest. PMID- 11766554 TI - A fair (hearing) wind is blowing. PMID- 11766555 TI - Pasteur returns. PMID- 11766556 TI - Anthrax. PMID- 11766557 TI - Old biological threats. PMID- 11766558 TI - White lesions on the lip. PMID- 11766559 TI - Herpetic neuralgia. Use of combination therapy for pain relief in acute and chronic herpes zoster. AB - Herpes zoster (shingles) is a localized infection that begins in the dorsal root ganglla of the cranial or spinal nerves and spreads as a rash over the corresponding dermatome. It usually is caused by reactivation of latent varicella zoster virus remaining from childhood chicken pox. Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome that occurs as a complication of shingles, most commonly in older persons. Acute zoster and PHN can be severe conditions associated with impaired sleep, decreased appetite, depression, anxiety disorder, and diminished libido. Management of zoster-related pain should begin as soon as possible after the onset of symptoms. Combination therapy--including antiviral, antidepressant, corticosteroid, opioid, and topical agents--provides the most effective analgesia. PMID- 11766560 TI - Ophthalmology. Screening and treatment of age-related and pathologic vision changes. AB - In the older adult, deterioration of normal vision is caused by age-related physiologic and pathologic changes. Vision impairment undermines quality of life by reducing independence, mobility, and the enjoyment that goes with seeing clearly. The most common causes of vision impairment are age-related macular degeneration (AMD), glaucoma, cataract, and diabetic retinopathy. Key to successful management of vision impairment is early detection of signs and symptoms, patient education regarding preventive strategies, and swift medical or surgical intervention for established or emerging conditions. Vision rehabilitation is an important management option. PMID- 11766561 TI - Posttraumatic stress. Helping older adults cope with tragedy. PMID- 11766562 TI - [Dynamics of community structure in successional process of needle and broad leaved mixed forest in Heishiding of Guangdong]. AB - This paper dealt with the dynamics of community structure in a ten-year succession of needle and broad-leaved mixed forest in Heishiding of Guangdong Province. The vertical community structure tended to be complex, while the horizontal one increased by a wide range. There was no big change in species composition, but the dominance of conifers Pinus massoniana and Cunninghamia lanceolata was substituted by the broad-leaved species, such as Schima superba, Symplocos adenophylla and Schefflera octophylla. The whole community changed from needle and boad-leaved mixed forest into broad-leaved and needle mixed forest. The species diversity and evenness of tree layer were increased, the ecological dominance was decreased, and the community became more complicated. PMID- 11766563 TI - [Vertical distribution and quantitative dynamics of dominant functional groups of arthropod community in rice fields and estimation of natural enemy effects]. AB - The study showed that Lycosid (wolf spider) mainly distributed in the basal part of rice plants, not as wide as we know in past. Tetragnathid did not limited in the upper part of plants, but might translate to middle or lower part when affected by insecticide. The relationship between the vertical distributions of top and basal species was not significant. Besides the amount of natural enemies, the spatial distribution characteristics of natural enemies and brownplanthopper, and the proportion of brownplanthopper to total preys of natural enemies were the factors affecting the role of natural enemies on the population dynamics of brownplanthopper in rice fields. A model to evaluate the effect of natural enemies to brownplanthopper was put forward, which included the message of quantitative dynamics, spatial distribution and feeding characteristics of natural enemies, brownplanthopper and neutral insects. PMID- 11766564 TI - [Evaluation of plant protectants against pest insects]. AB - An interference index of population control (IIPC) was constructed for investigating the complex effects of plant protectants, including the effects of repelling insect pests away from the plant, deterring the egg laying of adults and the continuation of feeding, and causing death by toxicity. At the same time, indicated by IIPC, the alcohol extracts of some common plants, such as Eucalytus rubusta, Wedelia chinensis etc. and the neem oil gave very good results to protect the plant against Plutella xylostella. The D-C-Tron NR Petroleum Spray Oil (CALTEX) also gave an excellent effect to protect citrus against red mite. All the experiments show the important role of the repellent effect on the pests. PMID- 11766565 TI - [Effect of temperature and food on Spodoptera litura population]. AB - The relationship between temperature and development of Spodoptera litura was simulated by the sine model V(T) = A + B sin(C0 + C1eC3T + C2e-C3T), and the threshold temperature and thermal requirement for its development at different stages were estimated by the direct optimum method. The model for the relationship between temperature and survival rate was fitted by the experimental data. The theoretical optimum temperature for the development of eggs, young instar larvae, old instar larvae and pupae was 26.7, 24.7, 24.9 and 25.8 degrees C, respectively. The life table parameters under different feed conditions (cabbage, lotus, sweet potato, soybean leaves) were estimated by the method of bisexual life table with age-structure. At temperature 25 degrees C, the intrinsic rates of increase under the four different feed conidtions were 0.1836, 0.1719, 0.1778 and 0.1206, respectively. PMID- 11766566 TI - [Response of Capsicum frutescens metapopulation to simulated insect herbivorous behaviors]. AB - Based on the theory of metapopulation, this paper studied the response of different leaf-cutting Capsicum frutescens metapopulation to simulated short-term insect pestes during high temperature period in July. Variance analysis (ANOVA), principal component analysis(PCA) and plant growth analysis were applied. The result shows that C. frutescens had a strong compensatory ability. The number, dry weight and leaf area of old leaves decreased with increasing leaf-cutting, but contrarily for new leaves. The total leaf number did not show any significant difference, but the total area and weight of leaves were significantly different, because of the influence of old leaves. The number, weight and lenght of branches were not significantly different with different treatments, and the number of fruits, flowers and flower buds also showed no significant difference. However, the difference of their dry weights was significant. It is practical to use number indexes, but not dry weight, leaf area and length for plant growth analysis in metapopulation, when the difference of dry weight between modulars is small. It is suggested that a certain degree of herbivory might be beneficial to the growth and fruit yield of C. frutescens during the high temperature period. PMID- 11766567 TI - [Effect of Bacillus megaterium on Gluconobacter oxydans in mixed culture]. AB - To reveal the relationship between Bacillus megaterium and Gluconobacter oxydans in the mixed culture of vitamin C two-step fermentation, the effect of B. megaterium on the growth of G. oxydans and its synthesizing ability of 2-keto-L gulonic acid(2KGA) was studied. The bioactive metabolites which could enhance the synthesis of 2KGA were isolated and purified by ultrafiltration, gel chromatography and SDS-polyacrylamide gel electrophoresis. Both the culture supernatant and the cytosol of B. megaterium could promote the proliferation of G. oxydans, and the active component in the culture supernatant was above 100 KDa. The culture suernatant could enhance the conversion of L-sorbose to 2KGA, while the cytosol could not. The active components in B. megaterium culture supernatant had molecular weight of 30-50 KDa and above 100 KDa, and the former was a kind of protein with an apparent molecular weight of about 35 KDa, which consisted of one sort of subunit and contained Fe and Zn elements. PMID- 11766568 TI - [Wetland ecosystems formation and its protection in Yellow River Delta]. AB - Site investigation, satellite photo analysis and historic material analysis show that the vast neonatal wetlands in Yellow River Delta were created by high concentration sediment of the river and the land-sea evolution. Affected by the regional climate, landform, geological deposition, soil, vegetation and their interactions, the wetlands covered 4.5 x 10(5) hm2, 6.84 x 10(4) hm2 of which were artificial wetlands. The wetland ecosystems changed with the waving of the Yellow River Mouth and the land development in the Delta area. From ocean to land, the sublittoral aquatic wetland, eulittoral wetland, eplittoral salt wetland, bulrush-quitch wetland, meadow wetland and land agroecosystem were developed. The wetland ecosystems had abundant biological resources, including 1524 wild animals, 300 birds and 1040 fishes, which were changed recently by the oil development and affected by the interruption of Yellow River. Wetland protection should be strengthened in resources utilization. PMID- 11766569 TI - [Landscape heterogeneity of urban vegetation in Guangzhou]. AB - Seven indexes were used to study the landscape heterogeneity of vegetation in Guangzhou City. The results show that the patch density was 11.8 patches.km-2 and the line corridor density was 1.87 km.km-2. In old urban area, the vegetation landscape was characterized by small patches, heavy fragmentation, high diversity and random distribution, showing a highly heterogeneous spatial pattern, while in new urban area, the vegetation landscape was characterized by big patches and even distribution. Therefore, when the size of vegetation area was the same, the even distribution of vegetation could improve the landscape heterogeneity and make the ecological function more effective. PMID- 11766570 TI - [Light effect of gaps in Huangshan pine community and regeneration of Huangshan pine]. AB - This paper dealt with the gaps of Huangshan pine(Pinus taiwanensis) forest developed on the meadow of 1400-1600 m above sea level of Huangshan Mountain. The method of analyzing annual ring growth of pine trees surrounding gaps was employed to estimate the time of gap formation, which was almost the same as the regeneration occurred there. The dynamic variations of total radiation and photosynthetic available radiation(PAR) at different points in gaps were measured, and a regression model for their estimation based on gap size, expanded gap size and canopy closure situation overhead the extended gap was established. The results indicated that the total radiation and PAR were respectively 90% and 71% of full sunlight in gap center, and 30-40% and 25-33% in expanded gaps, while the light under canopy was less than 10% of full sunlight. In the gaps with an area of 40 m2 or in the extended gaps with an area of 110 m2, the light might basically satisfy the growth of the pine, and the gap regeneration could occur. It is suggested that man-made gaps could be made to facilitate the regeneration of Huangshan pine, which could be used as a management approach for Huangshan pine forests, and also for maintaining the landscape in beauty spots of Huangshan Mountain. PMID- 11766571 TI - [Parasitic metamorphosis development of Lamprotula fibrosa]. AB - The glochidia of Lamprotula fibrosa develop to maturity in the outer gill of female and are expelled to the outside in winter, and then, the mature glochidia are parasitized to the gill of fish host and start the parasitic metamorphosis development. The parasitic period lasts about 4 months. The inner and outer byssuses disappear after parasitizing for 3 days. The foots develop after 35 days. The intestine, adductor muscle, nephridium and gill anlage develop after 90 days. The shells become thick and protrusive. The glochidia become larvae with a size of 253.37 x 273.26 x 179.96 microns in the next spring, then leave the gill of fish host, and start their independent life. PMID- 11766572 TI - [Influence of fluctuating ecological factors on male occurrence of Moina macrocopa]. AB - Studies with clonal culture show that female M. macrocopa did not produce male progeny directly, or, in other words, the parthenogenetic(amictic) female could not transform into microtic(amphoteric) female, when suffered from one-off acute or durative progressive stimulation. Under durative progressive stimulation by illumination, temperature, food density or pH, the intrinsic rates of increase were 0.7748, 0.7481, 0.6539 and 0.6310 d-1 ind-1, 0.9%, 4.0%, 16.4% and 19.3% less than the control, respectively, indicating that the animal was more sensitive to the fluctuation of food density and pH followed by temperature. PMID- 11766573 TI - [Numerical dynamics of sediment bacteria in shrimp polycultural ecosystems]. AB - The numerical dynamics of sediment bacteria was studied from May to September 1997, in the Shrimp Farm of Huanghai Fisheries Group Corporation with five experimental enclosures. It shows that the numbers of sediment bacteria ranged from 4.10 x 10(8) to 12.36 x 10(8) cells.g-1, averaged 8.09 x 10(8) +/- 2.17 x 10(8) cells.g-1, and increased gradually with increasing cultural time. The maximum was in 0-1 cm layer, and decreased obviously bellow 2-3 cm layer. PMID- 11766574 TI - [Biological purification of saline chemical wastewater and variation of algological indicatiors]. AB - Simulation pond experiment shows that from the entrance to the exit of the pond, the concentration of pollutants was decreased, while the species, diversity index and primary productivity of algae were gradually increased with increasing purification duration. The dominant algae species changed from high tolerance species to medium tolerant species. Algae quantity and chlorophyll-a concentration remarkably increased. Through 32 days, the purified water flowed out from the third grade pond. The relationships between algae quantity, biomass and chlorophyll-a concentration and the contents of BOD5, COD, NH3-N and PO4-P could be described with the second order equation. Temperature had an obvious effect on the algae growth and purification effectiveness. The optimum temperature condition for algae growth and wastewater purification was in the range of 20-25 degrees C. PMID- 11766575 TI - [Ecological effect of CdCl2 on plasmid and role of plasmid in Cd-tolerance of its host]. AB - After treating the plasmid of Escherichia coli HB101 by CdCl2 in vitro or in vivo, the effect of Cd on the structure of plasmid pWH58 DNA was studied through argarose gel electrophesis and restriction fragment length polymorphism analysis. By comparing the growth of E. coli with and without plasmid cultured in the medium with Amp LB and non-anti LB under different concentrations of CdCl2, the effect of Cd on plasmid E. coli of in vivo and the role of plasmid in Cd tolerance of its host were studied. Cd treatments of E. coli in vitro or in vivo didn't cause an obvious change of the structure of plasmid pWH58 DNA. Plasmid pWh58 could replicate for regeneration and gene express under Cd stress. Plasmid pWH58 of E. coli in vivo lowered Cd-tolerance of its host form 75 mg.L-1 to 50 mg.L-1. Cd-tolerance of E. coli ascended markedly after Cd taming, but had a trend of reversing to original level after restoration, indicating that Cd tolerance of E. coli could be tamed, but the tamed Cd-tolerance still had no genetic basis. PMID- 11766576 TI - [Dynamic features of some biochemical constituents in Gynostemma pentaphyllum under different environments]. AB - With biochemical techniques, the authors preliminarilty examined the dynamics of polyphenols, free amino acids and water-soluble sugars in Gynostemma pentaphyllum collected from different regions and the relationships between them and climate factors. The dynamic patterns of these three types of constituents in stems, blades and shoots under the same environment were different. At different growth phases, stems and blades had different contributions to the constituents. The dynamics of them differed with their environments. Polyphenols, free amino acids and water-soluble sugars might regulate the growth and development of plants. Moreover, they were characterized by plasticity, and the dominant climate factors affecting the dynamics of the constituents varied greatly. PMID- 11766577 TI - [Continuous cropping obstacle and rhizospheric microecology. II. Root exudates and phenolic acids]. AB - This paper discussed the effect of main crop root exudates the relationship between the kinds and amounts of root exudates and the growth of different kinds of crops and their environments. From the aspects of the decompostion of crop residues and the excretion of root systems, the source, form and adsorption mechanism of soil phenolic acids and their effect on crop growth and soil bio activity were also elaborated. PMID- 11766578 TI - [Utilization of municipal sludge in agriculture and sustainable development]. AB - Based on the ideas of sustainable development, this paper analyzed the features and disposal situations of municipal sludge and its influence on agricultural and urban development. It is suggested that the land application of municipal sludge is significant and urgent for urban and agricultural sustainable development. Land application of sludge will also be basic outlet for sludge disposal in the future. The key of land application of sludge lies in controlling the content of toxic pollutants in sludge and utilizing sludge scientifically. PMID- 11766579 TI - [Spectral characteristics of solar radiation in broadleaved Korean pine forest in Changbai Mountain]. AB - Based on the measurement above and below forest canopy and meteorological data, the spectral characteristics of solar radiation in broadleaved Korean pine forest in Changbai Mountain was analyzed. The results show that the photosynthetically active radiation(PAP) coefficients of total radiation, direct radiation and scatter radiation changed daily and yearly, with an annual averages of 0.46, 0.43 and 0.56 respectively. The average reflectivity, transmissitvity and absorptivity of single leaves of different tree species in Korean pine forest were 27.0%, 23.4%, 49.6% respectively. Single leaves nearly absorbed all of the ultraviolet radiation(UV) and 71.8% of photosynthetically active radiation, but transmitted 9.6% and reflected 18.6%. As for near-infrared radiation (NIR), the reflectivity and transmissitivity of leaves were a little less than the absorptivity. The forest canopy absorbed 93.9% PAR and 94.1% UV, but reflected and transmitted less. It absorbed 59.2%, reflected 26.3% and transmitted 14.4% NIR. PMID- 11766580 TI - [Seed rain and seed bank of constructive species in evergreen broadleaved forest at Chongqing Simian Mountain]. AB - The study shows that the early and late seed rains of constructive tree species in evergreen broadleaved forest at Chongqing Simian Mountain had no activity. The bigger the seeds of the species and the earlier or later the seeds of the species matured, the higher the proportion of the seed rain damaged by animals. The quantitative variation of seed rain, active seed rain and seed bank did not take place at the same time. At early time, the number of seed banks of Castanopsis fargesii, Lithocarpus glabra, Quercus myrsinrefolia, Castanopsis plasyacantha, Cinamomum subavenium which own more active seed rain increased by geomitric series. The seed banks of Castanopsis orthacantha and Schima argentea were small, only survived a short time, and did not sprout next year. The quantitative dynamics of seed banks and their increasing or decreasing rates were decided by the proportion damaged by animals, dying speed of seeds and their resistance to pathogens and adverse circumstances, and the state of seed germination. PMID- 11766581 TI - [Relationship between flooded situation and poplar growth on beach land of Yangtze River in Anhui]. AB - Through the analysis on the dynamics of flooding and the annual ring series of poplar trees on the beach land of Yangtze river in Anhui in the period of 1989 1997, the related models on flooded situation and ring growth were built. The results showed that there existed significant differences in flooding time and depth on different elevations of beach land, which made a great influence on the annual ring growth of poplar trees. The maximal flooded depth was more important than flooded time for its influence on ring growth. In addition, the flooded situation in August and September of previous year had a significantly negative influence on the ring growth of current year. The beach land with a maximal flooded depth of more than 2 m was not suitable for high-productive plantation of timber. It is suggested that a little more dense plantation should be managed for the production of pulp materials. PMID- 11766582 TI - [Population density of Eucalyptus urophylla plantation]. AB - This paper dealt with the relationships and correlation models of the population density of 5.6 years old Eucalyptus urophylla plantation with its crown width, diamter at breast height(DBH), tree height, individual standing volume, stand volume, wood properties and survital rate. The results showed that the population density remarkably affected DBH, individual standing volume, crown width, live branch height, stand volume and wood fiber width; but not affect tree height, basic density of wood, and length of wood fibers. It had a positive relationship with stand volume, live branch height and wood fibers width, and a negative relationship with DBH, individual standing volume and crown width. In addition, E. urophylla had a wide range of reasonable density. For short-rotation puplwoods, the optimum planting density of E. urophylla is 2000 individuals per hectare. PMID- 11766583 TI - [Mixing of Cunninghamia lanceolata with Michelia macclurei and restoration of self-sustaining mechanism in G. lanceolata plantation]. AB - The formation of self-sustaining mechanism is one of the major objectives for the sustainable management of plantations. In this study, the incorporation of different proportions of native Michelia macclurei into Cunninghamia lanceolata plantation was practiced to restore the degraded C. lanceolata plantation, and the comparison of nutrient cycling characteristics and soil nutrient concentrations was made among four types of plantation stand with different mixed rate of native M. macclurei representing four different restoration stages of degraded C. lanceolata plantations. With the increase of the proportion of M. macclurei in the plantation, the litterfall and returned nutrients N, P, K, Ca and Mg increased. The nutrient cycling efficiency increased significantly, e.g., that of N and Mg increased from about 0.1 for the degraded pure C. lanceolata plantation to above 0.5 for the pure M. macclurei plantation. Soil organic matter and nutrients also elevated. It is suggested that the self-sustaining mechanism of the C. lanceolata plantation forest gradually reformed as the proportion of native M. macclurei mixed in the plantation increased. The criteria to determine the proportion of native broad-leaved tree species mixed in C. lanceolata plantations for the purpose of sustainable management should be based on whether the self-sustaining mechanism was reformed and whether the soil nutrient status was improved. PMID- 11766584 TI - [Distribution patterns of root systems of main planting tree species in Weibei Loess Plateau]. AB - The vertical patterns of root systems of Pinus tabulaeformis, Robinia pseudoacacia, Platycladus orientalis, Pinus sylvestris var. mongolica, Pinus armandi, Prunus armeniacia var. ansu planted in the Weibei Loess Plateau were studied with soil auger. Site conditions had a significant effect on the vertical root distribution of R. pseudoacacia, of which, soil moisture is the key factor. Soil species and soil structure also had great effect on the distribution. P. tabulaeformis had a maximum rooting depth at its young stage(8 years old), but the root density increased with age. There was a great difference in vertical root distribution among the tree species, of them, R. pseudoaccia rooted deepest, which negated the opinion that R. pseudoacacia is a shallow rooted tree species. According to the vertical root distribution of the tree species, the productivity of these species in the south-facing site of yellow loess soil would be in order of R. pseudoacacia > Prunus armeniacia var. ansu > P. tabulaeformis > P. sylvestris var. mongolica > P. armandi > Platycladus orientalis. PMID- 11766585 TI - [Decomposition process of Chinese fir stump roots and changes of nutrient concentration]. AB - With space as a substitute for time, the changes of the density of stump sapwoods and heartwoods, and the releasing process of major nutrients during the decomposition of Chinese fir stump roots were investigated. The yearly loss rate of the densities of sapwoods and heartwoods was 2.767 x 10(-2) and 2.255 x 10(-2) respectively during decomposition. The contents of N and P in sapwoods and roots decreased continually, while those in heartwoods increased during the first stage of decomposition, and then decreased. The K concentration in stump roots decreased remarkably during first two years, and the content of organic substances decreased during the whole decomposition process. The N, P and K concentrations in roots, were higher than those in stump sapwoods and heartwoods at the beginning of decomposition, but bet content of organic substance was opposite. PMID- 11766586 TI - [Response of broadleaved Pinus koraiensis forests in Xiaoxinganling Mt. to global climate change--a dynamic modeling]. AB - In this paper, the Forest Gap Model and four General Circulation Models (GCMs) were employed to investigate the dynamic response of broadleaved Pinus koraiensis forests in Xiaoxinganling Mountains of China to global climate change. Under CO2 doubling which was simulated by the scenarios of Oregon State University and Goddard Institute for Space Studies, the biomass of broadleaved Pinus koraiensis forest increased and the current Picea-Abies-broadleaved Pinus koraiensis forest would gradually develop to Betula costata-Tilia amurensis-Ulmus laciniata broadleaved Pinus koraiensis forest. Under the scenarios of Geophysical Fluid Dynamics Laboratory at Princeton University and United Kingdom Meteorological Office, Pinus koraiensis and other coniferous species would be replaced by broadleaved species such as Quercus mongolica, Tilia amurensis and Ulmus laciniata, and the broadleaved Pinus koraiensis forest would change to broadleaved forest, due to the great range increasing temperature by the scenarios. The future warming rate would determine the succession of broadleaved Pinus koraiensis forest. PMID- 11766587 TI - [Relationship between main vegetation types and climatic factors in Inner Mongolia]. AB - The relationship between main vegetation types and climate factors in Inner Mongolia was analyzed by using up-to-date vegetation map, statistics, modeling and spatial simulation of regional climatic factors under the support of GIS. The feasible climatic range of spatial distribution of plant communities was derived from overlaying vegetation map and climate maps. The results showed that the vegetation distribution was obviously in accordance with climate. On the one hand, all the types, not only zonal vegetation, but also mountain, sandy land and low land communities changed gradually from east to west due to the distance to oceans, with a zonal differentiation, Precipitation played an important role in determining this regulation. On the other hand, latitudinal replacement of plant communities occurred with the change of temperature from north to south. In addition, temperature was also the key factor controlling the spatial distribution of vegetation types, such as meadow, steppe, shrub and low land communities on the east and west sides of Daxinganling Mountains. PMID- 11766588 TI - [Individual biomass of natural Pinus densiflora]. AB - The aboveground biomass of individuals with different growth potentials in natural Pinus densiflora forest with different stand densities was measured in Yanbian, Jilin Province. The variation of individual biomass affected by densities was in order of dominant tree < intermediate tree < suppressed tree, while the distribution proportion of biomass in different organs affected by densities was: in order of trunk > branch > needle > bark. The biomass components of P. densifliora with different growth potentials varied markedly with the approaching of density class III, and the change of intermediate trees was similar to the whole stand. The vertical distributions of biomass of different trees were different from each other, but all showed that the biomass of trunks and barks was mainly distributed below 6 m high from ground, that of branches was within 6-10 m high, that of needles was uniform in the upper, middle and lower layers, and that of branches and needles in upper layer was least affected by density. PMID- 11766589 TI - [Comparison of physiological characteristics of different ecotype plants]. AB - Studies on the responses of photosynthesis, leaf water content and stoma resistance of 4 different ecotype plants to water stresses showed that their mechanism of drought-resistance was different. Mesic plants limited water loss from transpiration by increasing their stoma resistance, while xeric plants decreased water loss by keeping the high concentration of cell protoplasm. The latter had a higher efficiency of keeping water than the former. The leaf water content and stoma resistance was decreased from mesic to xeric plants, while the net photosynthetic rate per unit leaf was increased, indicating the difference of physiological characteristics among different ecotype plants. PMID- 11766590 TI - [Effect of cutting on vegetation composition and soil properties]. AB - Different cutting experiments were executed on well-grown natural Imperata cylindrica vegetation in red soil region. The biomass of every 6 years cutting was the highest, and the annual cut was the lowest. Annual cutting resulted in the highest total accumulative biomass in 6 years, with a total production of 399.1 kg per plot. The species composition was also influenced by the length of cutting period. In the 6th year of experiment, the xylophyta biomass in the treatment of every 6 years cutting accounted for 41.5% of the total biomass, while the herb biomass in the treatment of annual cutting was 99.0% of the total. The length of cutting period also influenced the layer's development of soil profile and the physicochemical properties of soil. In comparing with the treatment of annual cutting, the soil bulk density in the treatment of every 6 years cutting was lower, and the contents of soil organic matter, total nitrogen, available phosphorus and available potassium were higher. PMID- 11766591 TI - [Species composition and distribution of algae in semi-desert algal crusts]. AB - Twenty-two species of algae, including 10 Cyanophyta, 4 Chlorophyta, 6 Bacillariophyta and 2 Euglenophyta, were isolated and identified from the semi desert algal crusts in Shapotou, Ningxia Autonomous Region. The relationship between algae and soil matrix was studied by grinding and superprobe, and the distribution of algal species in eight layers of crusts was examined under light and scanning electron microscopes. It was found that the algae exhibited a layer typed distribution in intermicron, and the layers of algal crust from surface to inner were in order of inorganic mineral protection layer(ca. 0.02 mm), alga enriched layer(0.02-2.5 mm) and sparse algae layer(2.5-5.0 mm). The filaments of algae were united with clay mineral by the polysaccharides and protein of their sheath, or extended directly into mineral granules to network and band sand and soil particles. PMID- 11766592 TI - [Application of Quantitative Theory I in commenting the relationship of forage species and weed species]. AB - Quantitative Theory I was applied to evaluate the influence of managing measures on the relationship of pasture grass and weeds on two typical grasslands of south China. Grazing intensity and fertilizer dosage were the key factors affecting the dominance of pasture grass. The main weed species were E. odoratum, E. rubiginosum, H. perforata, I. anlindrica and E. annua. The suitable density of cattle was 1-4 cattle.hm-2, and the dosage of fertilizer application was 500-1000 kg.hm-2 for superphoshate, and 150-250 kg.hm-2 for KCl. PMID- 11766593 TI - [Distribution and transferring of carbon in kast soil system of peak forest depression in humid subtropical region]. AB - Taking Guilin Yaji Karst Experiment Site as an exemple and with the methods of field monitoring and laboratory analysis, this paper studied the distribution and transferring of carbon in the karst soil system of peak forest depression in the humid subtropical region of China. The carbon pools in biomass, litters and soil organic matter(SOM) and their mobility as expressed by oxidizability and decomposition rate of SOM, the concentration of soil CO2 and the emission rate of CO2 from soil were investigated. The mobile carbon pool in the system supplied a rich source of CO2, which drived the karst process. When active karst process happened in Spring and Summer, over 60% of carbon in the output water was derived from soil CO2, as traced by delta 13 C distribution in the system. Therefore, owing to the carbon transfer in the pathway of air-plant-soil-water, karst process took place rather under soil-rock-water interface than under air-rock water interface. Thus, the epigenetic karst process was driven and accelerated by soil as an interface of carbon environmental geochemistry. PMID- 11766594 TI - [Effect of modified ammonium bicarbonate on nitrification-denitrification process and NO and N2O emission]. AB - Compared with ammonium bicarbonate(AB), the effect of modified ammonium bicarbonate (MAB) on nitrification and denitrification processes and NO and N2O emissions in a clay soil (C soil) and a loam soil (L soil) was studied in laboratory (25 degrees C and 50% WFPS). The inhibition effect of DCD from MAB on nitrification was relatively small in C soil, but considerably great in L soil. Compared with AB, MAB extended 7 days and 33 days for retaining NH4+. During 15 days, the NO emission from C soil and L soil respectively accounted for 0.60% and 1.06% of applied N under AB application (100 micrograms N.g-1), which were as 30 and 12 times as the N2O emission from corresponding soils. After applying MAB, the emission of NO from C soil and L soil decreased by 67% and 95%, and the emission of N2O decreased by 64% and 95%, respectively. After 39 days of aerobic incubation, then anaerobically flooded incubation with nitrate addition (200 micrograms KNO3-N.g-1) for 7 days, the total loss of denitrification in MAB in L soil was 50% less, and N2O emission was 113% more than in AB in same soil. PMID- 11766595 TI - [Genetic effect of panicle traits of intersubspecific crosses of rice (Oryza sativa.) and its interaction with environment]. AB - The models of genetic effects and genotype x environment interaction for Additive Dominant-Additive x Additive epistasis were used to analyze the panicle traits of intersubspecific crosses of rice (Oryza sativa.) in different environments. It was found that significant additive, dominant and additive x additive epistatic effects and genotype x environment (GE) interaction were observed in main panicle length, spikelet density, primary branches, total lengths of primary and secondary branches, but the numbers of main panicle and secondary branches showed no significant additive x environment (AE) interaction and dominant x environment (DE) interaction. The seven traits studied were mainly controlled by dominant effects, but branches traits were more obviously affected by DE interaction. Heritabilities analysis showed that the general heritability in broad sense (HG2) was much larger than other heritabilities. To certain extent, the interaction heritabilities showed their effects in seven panicle traits tested. Heterotic prediction indicated a positive heterosis in all panicle traits except the numbers of primary and secondary branches. GE only influenced the expression extents of heterosis, but was not able to change their directions. According to the predicated genetic effects, IR66158-37, IR65600-85, Minhui63 and R669 were better than other parents in the tactics of breeding for improving panicle traits, because the progenies from these crosses always showed that panicle traits were slightly affected by environment. PMID- 11766596 TI - [Pot experiment on effect of clipping at seedling stage on spring wheat]. AB - Pot experiment on the compensatory effects of spring wheat(Triticum aestivum) at different clipping intensities (simulating herbivory) at seedling stage (three leaves) was conducted in semiarid region of Gansu Province. Under two conditions of 60% and 90% of field water-holding capacity, spring wheat growth was stimulated by clipping at seedling stage, resulting in overcompensation in biological and economic yields, and with more compensation for heavy clipping than light clipping. The overcompensation of the spring wheat was at the cost of more water consumption. PMID- 11766597 TI - [Relationship of NO3(-)-N, NO2(-)-N accumulation in some crop seeds with N fertilizers application]. AB - From 1996 to 1997, the effect of applying organic and chemical fertilizers on NO3 and NO2- accumulation in crop seeds was studied in four green food bases of kidney beans (Yunan Province), red small beans (Hebei Province), soybeans (Heilongjiang Province), and peanuts (Shandong Province). For kidney beans and red small beans, the highest grey correlation was existed between available N in soil and NO2- in seeds, no matter whether organic fertilizer or urea was applied. In organic fertilizer trials, the highest grey correlation appeared in soil pool (between total N and available N) or seed pool (between NO3- and NO2-), while in chemical N fertilizer trials, it existed between total N in soil and NO3- in seeds. For kidney beans and red small beans, the dynamics of NO3-/NO2- in seeds was different with the kind of fertilizers applied. Extremely significant negative linear correlation and positive linear regression were existed between the content of NO3- and NO2- in all four crop seeds. PMID- 11766598 TI - [Variation of dormancy characteristic of different Pinus bungeana seed sources]. AB - Studies on the dormancy characteristics of Pinus bungeana seeds from 7 representative seed sources show that the difference of water permeability of seed capsule was very significant among seed sources. The seeds from northern part of distribution area had a much higher water permeability than from the south. According to water permeability, the seven seed sources were divided into 2 geographical groups, with Qinling Mountain as the division line. The difference of seed ventilation was caused firstly by outer seed capsule, and secondly by inner one. The variation of permeability had a similar trend with the ventilation. The inhibition ability of seed extracts was significantly different among different seed sources, which was increased with the concentration of seed extracts. Based on the inhibition ability of extracts from seed capsule and endosperm, the seven seed sources were divided into 2 and 3 geographical groups, respectively. The germination capacity decreased with increasing latitude, and seeds with poor germination capacity took relatively more time for germination. All population groups based on different division criteria showed such a character, i.e., the difference of seed characteristics was more significant among groups than in same group, and the distance of seed source was longer among groups than in a group. The difference of dormancy characteristics of different P. bungeana seed sources was the result of interaction between climatic and geographical factors. PMID- 11766599 TI - [Effect of different source iron on piglet's growth, metabolism and environment]. AB - In order to approach the effect of different source Fe on piglet's growth, metabolism and environment, an experiment was conducted with 158 suckling pigs from 15 litters, which were randomly allocated to group I, II and III, and fed with diet I (basal diet + FeSO4.H2O), II (basal diet + Fe-citric acid) and III (basal diet + Fe-methionine complex), respectively. Each of the diets contained 146 mg.kg-1 Fe. The results show that after the experiment ended, the body weight, daily increment, grades for appearance and behavior, hemoglobin concentration in blood, Fe-transferring albumen concentration in plasma, and Fe contents in plasma and liver of 35 days old piglets in group II and III were higher (P < 0.05 or P < 0.01) than those in group I, while the feed conversion, diarrhea incidence, fecal amount and its Fe content of the piglets in group II and III were lower (P < 0.05 or P < 0.01) than those in group I. The body weight and daily gain of the piglets in group III were also higher (P < 0.05) than those in group II, but no significant differences (P > 0.05) in other traits between group II and III. It is suggested that Fe-methionine complex and Fe-citric acid could improve piglet's health, growth and development, feed conversion, and physiological and biochemical parameters, increase the absorption and utilization of Fe by piglet's body, and decrease the fecal amount and its Fe content. Both of them should be effective and safe Fe sources for suckling pigs. PMID- 11766600 TI - [Insect community and its diversity in Mangrove forest at Yingluo Bay of Guangxi]. AB - The insect community and its diversity in mangrove forest at Yingluo Bay of Guangxi were studied in 1995-1996. The results show that there were 195 insect species in the mangrove area, dominated by Crematogaster rogenhoferi, Camponotus tokioensis and Dichocrocris chorophanta. The diversity of insect community was higher in the inside beach than in the middle and outside beaches. Tides and windstorms were the important factors that decided the community composition levels. The principal component affecting the diversity was the species evenness in the inside, middle and outside beaches. PMID- 11766601 TI - [Mating behavioral ecology of Ancylis sativa adult]. AB - The study shows that the mating peak of the overwintering generation adults of Ancylis sativa appeared at 6.0-8.0 hours in their scotophase and the mating activity was more intensive during 2-3 days after eclosion. The higher the temperature was, the later the adults began to mate. For most adults, the duration of mating was 3-4 hours, with a mean frequency of 3.3 times for males and 1.59 for females. The mating behavior of 2-days old adults shifted from photoperiod 14L:10D to continuous dark was similar to that at 14L:10D, all showing an obvious rhythm. When the adults were shifted to continuous light, their mating became inacitive and irregular. The sex pheromone titer of virgin female decreased significantly after mating 1 hour, and remained low until 48 hours after mating. PMID- 11766602 TI - [Improving the level of liver transplantation in China]. PMID- 11766603 TI - [To strengthen the monitoring and research on clinical adverse drug reaction induced by Chinese medicines]. PMID- 11766604 TI - [Comparison of acute cellular rejection between living donor liver transplantation and cadaveric liver transplantation]. AB - OBJECTIVE: To compare the incidence and severity of acute cwellular rejection (ACR) between living donor liver transplantation (LDLT) and cadaveric liver transplantation (CLT). METHODS: 51 patients underwent LDLT among which 30 received the liver of blood-related donors, and 65 patients underwent CLT. Clinical data, such as the cold ischemic time of liver graft, use of immunosuppressive agents, ACR rate, response to steroid therapy, HLA matching between donor and recipient, and survival rates of liver graft and patients were collected and analyzed. RESULTS: The graft survival rate, patient survival rate, ACR rate, ACR multiple incidence rate, and no response rate to steroid therapy in CLT and LDLT groups were 72% vs 78%, 77% vs. 78%, 48% vs. 41%, 20% vs. 10%, and 11% vs. 4% (P > 0.05). The difference of ACR rates between CLT and living blood related donor liver transplantation was statistically insignificant. There was no significant difference in number of HLA allele mismatching between patients with ACR and those without ACR. The combined immunosuppression therapy rely mainly on FK506 use reduced the occurrence of ACR (P < 0.05). CONCLUSION: There is no marked difference in incidence of ACR between LDLT and CLT. ACR in liver transplantation is correlated to neither HLA matching between donors and recipients nor to cold ischemic time of the liver graft. FK506 avoids ACR better than cyclosporin2 A. PMID- 11766605 TI - [Establishment of model of aristolochic acid-induced chronic renal interstitial fibrosis in rats]. AB - OBJECTIVE: To study chronic renal interstitial fibrosis induced by aristolochic acid (AA) in animal models. METHODS: Female Wistar rats were divided into two groups: AA group (n = 42) peritoneally injected with AA (5 mg.kg-1.d-1) for 16 weeks and control group (n = 5) peritoneally injected with normal saline (2 ml/d) for 16 weeks. The body weight of rats was taken. At week 8, 12, 16, and 24 six rats were killed in the AA group. The five rats in the control group were killed at week 24. Specimens of lood and urine were taken before the animals were killed. Specimens of renal tissue were taken after the animals were killed. Twenty-four hour urine protein, urine beta 2 microglobulin (beta 2-MG), and renal function were tested regularly. Pathological examination, including tubulo interstitial area calculation, was made to the renal specimens. RESULTS: The body weight of rats in AA group became significantly lower than that of the control rats after 16 weeks' AA injection (P < 0.01). The blood urea nitrogen (BUN) and serum creatinine (Scr) in AA group increased significantly than those of the control group at the 16th, 20th, and 24th weeks (P < 0.05). Optical microscopy showed tubular-interstitial damage in AA group in 16 weeks. Renal tubular atrophy and multifocal renal interstitial fibrosis were shown in 24 weeks. The area of renal tubule increased and the area of the lumen remarkably decreased at week 16 compared with those in the control group. The area of renal tubule decreased remarkably and the area of renal interstitial greatly in the AA group at week 24. Electrical microscopy showed increase of primary and secondary lysosomes and diasappearence of part of brush border of tubular endothelial cells at week 16, and accumulation of secondary lysosome in cytoplasm at weeks 20 and 24 in the AA group. Histoimmunofluorescence showed that IgG, IgA, IgM, C3, and C1q were negative in the renal tissue of experimental animals. CONCLUSION: Animal models with chronic renal tubuloointerstitial nephropathy induced by aristolochic acid were successfully established. Aristolochic acid may have chronic toxicity to renal tissues, and cause chronic renal interstitial fibrosis in rats. PMID- 11766606 TI - [The clinical and pathological manifestations of aristolochic acid nephropathy- the report of 58 cases]. AB - OBJECTIVE: To realize and classify the aristolochic acid nephropathy (AAN) according to its clinical and pathological manifestations. METHODS: Fifty eight cases in our Division during October 1998 to August 2001 were reviewed, and their clinical, laboratory and pathological manifestations as well as the response of therapy were analyzed. The aristolochic acid (AA) component in some Chinese traditional drugs taken by our patients was detected with thin-layer chromatography (TLC) scan. RESULTS: AAN might be divided the following three types: (1) acute AAN (n = 4): acute tubular necrosis and acute renal failure were its pathological and clinical characters, respectively. (2) tubular dysfunctional AAN (n = 7): tubular degradation with atrophy, and renal tubular acidosis and/or Fanconi syndrome were its main pathological and clinical manifestations, respectively. (3) chronic AAN (n = 47): renal interstitial fibrosis with few infiltrated mononuclear cells, and chronically progressive renal failure were its dominant pathological and clinical findings, respectively. Steroid therapy was tried to treat some patients with AAN, and a few patients in the first two types obtained some good effects. AA component was demonstrated by the TLC scan in the drugs taken by our patients. CONCLUSION: Chinese traditional drugs containing AA are able to cause a special tubulointerstitial nephropathy which may be classified three types with different outcome. To definite effects of steroid on AAN still need to be proved by further studies. PMID- 11766607 TI - [Triptolide inhibits vascular endothelial growth factor expression and production by endothelial cells]. AB - OBJECTIVE: To investigate the effect of triptolide on vascular endothelial growth factor (VEGF) expression and secretion by endothelial cells, and explore the mechanism of anti-proteinuric effect of triptolide on glomerular nephritis. METHOD: A human umbilical endothelium derived cell line (ECV-304) from American Type Culture Collection(ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, and intracellular protein production and secretion induced by PMA were measured by RT-PCR, flow cytometry and enzyme linked immunosorbent assay (ELISA). The effects of triptolide on endothelial c-jun/c-fos mRNA expression were investigated by RT-PCR. RESULTS: 100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose dependent manner. Moreover, triptolide dose-dependently inhibited endothelial c jun/c-fos mRNA expression. CONCLUSION: Triptolide is a potent inhibitor of VEGF expression and production, suggesting that the inhibitory influence of triptolide on VEGF expression and production may be one of the mechanisms underlying its anti-proteinuric effect on glomerular nephritis. Triptolide might inhibit VEGF expression and production by interfering with transcription factor AP-1 formation. PMID- 11766608 TI - [Job strain and hypertension risk in Capital Steel and Iron Company in Beijing]. AB - OBJECTIVE: To assess the relation between the scales of Job Demand control Model (or "Job strain") and the prevalence of hypertension. METHODS: A standardized questionnaire base-line survey was conducted among 1,556 male and female employees aged 18-65 in two factories of the Capital Steel and Iron Company, Beijing, in 1997 to investigate the socio-demographic factors and job strain so as to identify the major risks of hypertension. RESULTS: The prevalence of hypertension increased from 6.5% to 21.2% with an age-adjusted relative prevalence ratio (95% CI) of 3.26 (2.30, 4.41) when the job strain pattern changed from high control and low demand to moderate control and moderate demand and further to low control and high demand among the male employees. After adjustment for confounding effects from age, education, body mass index, smoking, alcohol consumption, and physical activity, the odds ratio (95% CI) was attenuated to 2.31 (1.45, 3.81). Such a phenomenon was not typical among females. CONCLUSION: The risk of hypertension was elevated with the increase of job strain in men. PMID- 11766609 TI - [In vitro and in vivo experiment of transduction of reporter gene into tumors by E5 gene delivery system]. AB - OBJECTIVE: To investigate the spectrum of tumors into which the E5 gene delivery system can transduce reporter gene so as to establish a platform technology that one gene delivery system can be used to treat multiple types of tumors. METHODS: The E5 delecvery system was used to transduce reporter genes into various types of IGF I R positive tumor cell lines in vitro and into different IGF I R positive tumors transplanted subcutaneously in nude mice in vivo. The efficiency of trasduction was examined. RESULTS: The E5 delivery system transferred reporter genes into five types of tumor cells that over-express IGFIR in vitro and transferred reporter genes into different tumors transplanted subcutaneously in nude mice that over-express IGFIR in vivo too. The transduction rate was positively correlated with the expression rate of IGFIR. However, the E5 delivery system failed to transfer reporter genes into tumor cedll lines in vitro and the tumors transplanted subcutaneously in nude mice in vivo, both of which were without IGF I R expression. CONCLUSION: E5 delivery system has rather remarkable target-ability and extensive usefulness. It has the potentiality in gene therapy of cancer. PMID- 11766610 TI - [The significance of Titin antibody in diagnosing myasthenia gravis with thymoma]. AB - OBJECTIVE: To investigate the clinical significance of Titin antibody (Titin-ab) in diagnosing myasthenia gravis with thymoma (MGT). METHODS: Titin-ab and acetylcholine receptor antibody (AChR-ab) in the sera of 73 MGT patients with different thymic pathological patterns and 58 MG patients without thymoma (NTMG) were detected by ELISA. RESULTS: The positive rate of Titin-ab in MGT group was 76.7%, significantly higher than those of NTMG group, other neurologic diseases group and healthy control group (P < 0.01). The sensitivity of Titin-ab in diagnosis of MGT was significantly lower than that of CT scan or MR of thymus (P < 0.05), but the specificity of Titin-ab in diagnosis of MGT was significantly higher than that of CT scan or MR of thymus (P < 0.05). The positive rate of Titin-ab was mainly related to the thymic pathology and was the highest in the thymic epithelial thymoma (TET) subgroup (95.1%). There was no significant correlation between the positive rate of Titin-ab and the Masaoka's stage of thymoma (P > 0.05). The titer of Titin-ab was highly correlated to the titer of AChR-ab in MGT group (r = 0.496, P < 0.01), but not in MGH group (r = 0.385, P > 0.05). CONCLUSION: Detection of Titin-ab is a rather sensitive, specific, handy method in diagnosis of MGT (especially TET). It may play an important role in the pathogenesis of MGT. PMID- 11766611 TI - [Microvascular decompression for hemifacial spasm: experience of 215 cases]. AB - OBJECTIVE: To investigate the relationship between pre-operational etiological diagnosis of medically intractable hemifacial spasm (HFS) and patterns of offending vessels and the curative effect of microvascular decompression (MVD). METHODS: Two hundred and fifteen patients with medically intractable HFS underwent MVD under general anesthesia. Pre-operative MRI examination was made for all cases to exclude space occupying lesion and magnetic imaging tomographic angiography (MRTA) was conducted for 145 cases of them instead of routine MRI. RESULTS: Routine MRI failed to provide information about offending vessels except for ruling out mass lesions whereas MRTA revealed the offending vessels with a positive rate of 82.8%, thus helping make correct diagnosis and operation decision. Follow-up of more than two years showed that the surgical intervention achieved a high relief rate of 91.2% without major complication, and with a low recurrence rate of only 3.5% after averaging more than two years' follow-up. CONCLUSION: Pre-operative MRTA can replace conventional MRI as a best approach for pre-operational etiological diagnosis of facial spasm. It helps perceive the offending vessels before operation. Skilled microsurgical technique along with correct recognition and mobilization of offending vessels are a must to assure MVD a high efficacious and low risk treatment of choice for HFS patients. PMID- 11766612 TI - [Isolation and study of one novel full-length gene related to human glioma]. AB - OBJECTIVES: To obtain differentially expressed genes related to human glioma using cDNA microarray and make a preliminary study of one novel full-length gene. METHODS: Total RNA was extracted from human glioma tissues and normal brain tissues, and mRNA was used to make probes. After hybridization and washing procedure, the results of hybridization were scanned using computer system. One gene named 507E08 clone was subsequently analyzed by northern blotting, in situ hybridization, bioinformatics and radiation hybridization. RESULTS: Fifteen differentially expressed novel genes related to human glioma were obtained through four times of hybridization and scanning. Northern blotting and in situ hybridization confirmed that 507E08 clone was lowly expressed in normal human brain tissue and over-expressed in human glioma tissue. BLASTn and BLASTx analysis showed that the clone 507E08 was a novel full-length gene with the length of 2002 bp. This gene, called human ribosomal protein 14.22 gene, codes 203 amino acids and is located on chromosome 14 between D14S1066 Marker and D14S265 Marker. CONCLUSION: cDNA microarray technology can be successfully applied to identify differentially expressed genes with small amount of specimen, high quality, high speed, and high sensitivity. The novel full-length human ribosomal protein 14.22 gene may correlate with formation of human glioma. PMID- 11766613 TI - [Cytokine gene polymorphism and organ transplantation]. PMID- 11766614 TI - Bibliography of toxinology. PMID- 11766615 TI - [Getting functional information from your sequence by the use of protein signature databases]. PMID- 11766616 TI - Academic support for combination therapy in hypertension. PMID- 11766618 TI - Recommendations for the use of low-dose diuretics. PMID- 11766617 TI - Irbesartan prevents the progression of kidney disease or death in patients with type 2 diabetes and high blood pressure. PMID- 11766619 TI - Irbesartan slows the development of diabetic nephropathy by up to 70% in hypertensive diabetic patients. PMID- 11766620 TI - New data affirm the long-term safety of prevastatin. PMID- 11766621 TI - BodyStat 1500MDD body composition analyser. PMID- 11766623 TI - [Deglutition disorders in the elderly. Little known disorders that should not be ignored]. PMID- 11766622 TI - [An aggressive arthritis]. PMID- 11766624 TI - [Hopeful progress in arthrosis research]. PMID- 11766625 TI - [Transition from malum coxae senile to the arthrosis deformans concept. A summary of the best known theories and classifications]. AB - The disease of degenerative arthritis has been known for thousands of years. Paleopathology has provided findings of ancient degenerative alterations. Furthermore, physicians in classical antiquity described several forms of joint diseases. A challenging problem was the therapy, which was limited at that time. For centuries all joint diseases were subsumed under the term"rheumatism." In 1683 Thomas Sydenham, who suffered himself from gout, first differentiated this joint disease from the larger group of rheumatic joint diseases. Another early classification was undertaken by John Haygarth in 1779. He differentiated gout from malum coxae senilis and the chronic rheumatic diseases. The different theories and the resulting classifications were influenced by different disciplines such as surgery, internal medicine, pathology, anatomy, neurology, microbiology, and radiology. This investigation includes the time period from the early nineteenth century until 1925 when the word "arthrosis" was first used in a medical publication. This investigation is based on research at the library of the German Museum for Orthopedic History and Science as well on the systematic search for articles in different German journals such as Zeitschrift fur Orthopddie and Fortschritte auf dem Gebiet der Rontgenstrahlen. It includes almost all important books and publications about degenerative arthritis for this time period. In the past there were many different descriptions for degenerative arthritis. The establishment of X-rays and new methods in histology and microbiology and the aspect of biomechanical theories led to a better understanding of the different diseases. The authors tried to construct new classifications without the knowledge of the causal and formal pathogenesis. This is the reason for the large number of different classifications, which had to be revised after a short period of time. This publication gives an overview about the most important articles and books which led to the classification currently in use. PMID- 11766626 TI - [Molecular principles of induction and progression of arthrosis]. AB - From a morphological point of view, osteoarthritis is characterized by continuous loss of the cartilage matrix, an increased density of the subchondral bone, and partial involvement of the synovial compartment. Research activities are focussing on gene expression and gene regulation in normal and osteoarthritic cartilage to develop prognostic markers and new therapeutic strategies. In general, chondrocytes from normal adult articular cartilage show low metabolic activity. However in osteoarthritis, activation and differentiation of chondrocytes occur. Activation involves anabolic pathways such as an enhanced expression of type II collagen as well as catabolic patterns such as the increased expression of matrix metalloproteinases. These metabolic pathways are unbalanced, leading to insufficient cartilage architecture, unable to meet the requirements for mechanical stability and load compensation. In osteoarthritis, chondrocyte differentiation is characterized by the expression of type X collagen. Further differentiation stages have been observed as shown for the expression of osteocalcin, osteopontin, or alkaline phosphatase in articular cartilage. This altered expression pattern of chondrocytes is likely to influence the biochemical and biomechanical properties of the cartilage matrix. In conclusion, new analytic and comparative methods to analyze gene and protein expression offer powerful tools to elucidate candidate genes in osteoarthritis. Detailed information on the regulatory pathways will be the basis for modulation of chondrocyte behavior and, therefore, may lead to new therapeutic approaches in the treatment of osteoarthritis. PMID- 11766627 TI - [Epidemiological arthrosis research]. AB - Osteoarthritis is the most common joint disease worldwide. Epidemiological studies on the prevalence and incidence have documented the role of osteoarthritis in industrial populations. More extensive clinical studies not only focussed on the impact of osteoarthritis on the quality of life, but have also helped to classify this heterogeneous disease and define clinical subsets. Although the methods of epidemiological osteoarthritis research are not without problems, epidemiology has nevertheless clearly defined risk factors of osteoarthritis and evaluated environmental influences such as sports or occupation. Apart from that, epidemiology has also brought new ideas to basic science research and in particular to molecular research on the genetics of osteoarthritis. PMID- 11766628 TI - [Diagnosis of arthrosis]. AB - Pain and loss of function are the major clinical symptoms leading to the diagnosis of osteoarthritis (OA). Further clinical findings allow the diagnosis of OA with a high level of sensitivity and specificity at the hip, knee and hand. Standard x-rays of the joints confirm the definitive diagnosis while standard serological examinations are mostly only necessary for differential diagnosis. The analysis of synovial fluid is an important diagnostic tool. Many biochemical markers in the serum have been established for anabolic and catabolic substances, which play a role in the synthesis and degradation of bone, cartilage and synovium in OA. These are of high scientific interest, but play only a minor role in daily practise. At present no single clinically important biochemical parameter exists for the early diagnosis, treatment, control or prognosis of OA. PMID- 11766629 TI - [Conservative nonpharmacological treatment of arthrosis]. AB - There are different options for nonpharmacological therapies in osteoarthritis. An educational program and instruction of the patient are of major importance. There is evidence that manual physical therapy and exercise improve function and reduce pain in osteoarthritic joints. Thermal modalities are employed for short term pain relief and change the intra-articular temperature. Electrotherapy, ultrasound, balneotherapy, and acupuncture show positive therapeutic effects. Orthotics, braces, and wedged insoles may be beneficial in selected cases. Based on the present findings, further investigations are needed to prove the effectiveness of various methods in physical therapy and nonpharmacological approaches to the management of osteoarthritis. PMID- 11766630 TI - [Drug therapy of arthrosis]. AB - Osteoarthritis is one of the most common and economically important chronic diseases amongst adults, especially those of a senior age. There now exists a range of effective medications, which either alone or in combination can alleviate the symptoms of the disease and improve the quality of life. Because these medications are not always sufficiently effective and must sometimes be interrupted due to side effects, a large arsenal of active agents is necessary. Alleviation of pain and inhibition of inflammation are the primary goals of pharmacotherapy, whereby the objective is to return an active or transiently painful, decompensated osteoarthritis to a latent (silent, pain-free) condition. This therapeutic goal can almost always be accomplished by using analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), or intraarticular injection of glucocorticoids. The main problem in administering NSAIDs is their gastrointestinal toxicity,for which a prophylactic medication (e.g., simultaneous application of misoprostol or switching to a COX-2 selective NSAID) should be considered especially with risk groups. The newly developed COX-2 selective NSAIDs represent a true enrichment of our therapeutic options. The spectrum of indications for COX-2 selective NSAIDs should in the future correspond to that of older NSAID preparations, providing that no as yet unknown and serious side effects come to light from their use. Pharmacological results published until now confirm that a clinically relevant analgesic and/or anti-inflammatory effect is associated with the use of SYSA-DOAs (symptomatic slow acting drugs in osteoarthritis). However, no clinical studies exist which can positively confirm prevention of morphologically recognizable cartilage defects in man, or a slowing down or reversal of any progressively developing joint cartilage destruction by any individual medication. Neither the benefits, risks, pharmaceutical quality, nor composition of Orthokin are known, and for this reason its use can not be recommended. Pharmacotherapy should only be considered as one of the three pillars of a long-term,stage-adjusted, and individually customized therapy, the other two of which are represented by nonpharmacological measures and surgical treatment. PMID- 11766631 TI - [[Surgical intra-articular interventions in arthrosis]. AB - The reconstruction of weight-bearing joint surfaces has long been a challenge for the orthopedic surgeon. The statistical rise in life expectancy, the spread of high-risk sports and leisure-time activities combined with high demands for painfree joint function even in older age as a factor for contemporary quality of life are the demographic factors of the bone and joint decade announced by the WHO. Osteoarthritis represents a multifactorial, irreversible, often heterogeneous joint disease with joint destruction as the inevitable consequence. Conventional and innovative intra-articular operative methods for the treatment of osteoarthritis are presented and discussed. Tissue engineering stands for vitalizing tissue modification by modification of cellular and humoral mechanisms. Thus, new therapy options for curing degenerative joint diseases will arise in the future. Autologous chondrocyte transplantation (ACT) represents one of the first clinically established methods. The paradigm of treating osteoarthritis by the orthopedic surgeon will be multimodal in the future. Innovative techniques in the biotechnological sector provide a promising horizon. PMID- 11766632 TI - [Tissue reactions around loosened hip joint endoprostheses. A histological study of secondary capsules and interface membranes]. AB - Pseudocapsules and interface membranes from 142 consecutive revision surgeries of hip prostheses were histomorphologically analyzed including a semiquantitative grading of the wear particles from the prostheses and bone cement as well as the cell infiltrates. The implant duration varied between 3 months and 19.5 years. In 37% of the cases up to 6 months in situ, inflammatory cell infiltrates characteristic for early infection were seen. In 22% of the cases with longer implant duration, signs of late infection were found. In the tissues of the predominantly cemented prostheses, bone cement wear prevailed, which could be regularly detected after about 1 year. Polyethylene wear appeared to be the second most common foreign material. Metallic wear was found in only 18% of the cases. Ceramic wear was only seen in tissues around loosened prostheses with ceramic ceramic couples. Due to the material abrasion, a foreign body reaction rich in macrophages developed with minimal lymphocytic infiltration. The degree of these tissue alterations and the amount of wear particles showed a statistically significant increase with increasing implant duration. In contrast, fibrin exudates, hemorrhages, and metaplastic ossifications were not dependent on the length of time in situ. Differences in respect to the amount of wear particles were found between prostheses with ceramic and metallic heads. Prostheses with metal-polyethylene combinations generated approximately twice as many polyethylene wear particles as prostheses with ceramic heads. Among the metal-polyethylene couples, the bipolar prostheses showed a markedly increased polyethylene wear, some of them with extensive osteolyses. Deposits of calcium pyrophosphate were twice as common in pseudocapsules as in capsules from joints with degenerative arthrosis. Because of the increasing frequency of revision surgery, knowledge of the histologic changes around joint prostheses seems to be important as these changes may indicate complications and give information in respect to the biocompatibility of implant materials. PMID- 11766633 TI - [Prevention of thrombosis in hip prosthesis implantation]. AB - Deep venous thrombosis is one of the most common perioperative complications after total hip arthroplasty. Systemic anticoagulation has been the gold standard for prophylaxis of postoperative deep venous thrombosis. There is no doubt that early mobilization and the use of pneumatic compression devices decrease the overall deep venous thrombosis rate. Single postoperative prophylaxis may decrease the overall deep venous thrombosis rate to 15-20% and the proximal deep venous thrombosis rate to approximately 7%. However,the activation of thrombogenesis is mainly an intraoperative event. The position of the extremity during the implantation of the femoral component leads to obstruction of the venous outflow. At the same time, the coagulation cascade is activated and markers of thrombogenesis in the blood are increased. By combining intraoperative (hypotensive epidural anesthesia and intraoperative heparin) and postoperative (pneumatic compression devices and aspirin) prophylaxis of deep venous thrombosis, the total deep venous thrombosis rate is reduced to less than 10% and the proximal deep venous thrombosis rate is reduced to 2%. Patients with increased risk for deep venous thrombosis should receive Coumadin or low molecular weight heparin. In addition, hypotensive epidural anesthesia reduces the intraoperative blood loss and the need for postoperative blood transfusion. PMID- 11766634 TI - [Treatment of knee dislocation after callus distraction of the femur--a case report]. AB - We report on the therapy of a complete ventrocranial luxation of the knee joint with leg shortening of 20 cm, which had appeared after diaphyseal distraction osteogenesis in the left thigh at the age of 7 years. The patient presented herself in our clinic at the age of 14 years. After application of an llizarov external fixator,first the luxation was gradually repositioned and afterwards arthrodesis of the knee joint was carried out. After consolidation of the arthrodesis, we removed the external fixator and carried out a unilateral, diaphyseal callus distraction in the left femur. The consolidation of the distraction callus of 12 cm was completed after 9 months and the fixator was removed. At the age of 18 years, 2 years after the treatment was completed, the patient was free of pain and able to walk safely. The remaining shortening of the left leg amounted to 2.5 cm and was balanced in the shoe proportionately. PMID- 11766635 TI - [Liver biopsy in chronic hepatitis C. Histopathology, molecular diagnostic analysis, and implications for therapeutic management]. AB - Histological evaluation of liver biopsies is the gold standard for assessing the severity of liver disease in chronic hepatitis C. In conjunction with anamnestic and serological data, it provides critical information regarding prognosis and therapeutic consequences. Grading of the necroinflammatory activity and staging of the manifested fibrosis according to well-established scoring systems are the essential parameters of the histopathological report. The frequency of chronic hepatitis C necessitates awareness of coinciding liver damage by nutritional or drug toxicity, bile duct diseases, and hereditary hemochromatosis. Detection of hepatitis C virus (HCV) RNA directly from the formalin fixed, paraffin-embedded biopsy specimen is highly sensitive and offers help in cases of equivocal results of serological testing for HCV. PMID- 11766636 TI - [Diagnosis of seronegative chronic hepatitis in tissue]. AB - The evaluation of a liver biopsy in chronic hepatitis should make a statement on the etiology and report the degree of activity and stage of the disease. The category of so called seronegative chronic hepatitis may include cases of chronic hepatitis C or infection with other viruses such as the Epstein-Barr virus (EBV) and cytomegalovirus (CMV), cases of marker-negative autoimmune hepatitis as well as drug-induced injury and Wilson's disease in younger patients. In order to establish the diagnosis, sensitive techniques of molecular biology should be applied as well as copper staining by histochemistry. Exact and detailed histopathologic analysis can reveal certain features of autoimmune hepatitis or drug injury. PMID- 11766637 TI - [Chronic cholangitis]. AB - The term chronic cholangitis comprises a heterogeneous group of intra- and/or extrahepatic diseases that may either be bacterially caused or immunologically mediated. In this review, we will focus on the latter and present the clinicopathological and pathogenetic aspects of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The histopathological criteria are defined and differential diagnosis is discussed. Particular emphasis is given to overlap syndromes of PBC and PSC with autoimmune hepatitis. Finally, a diagnostic algorithm is presented. PMID- 11766638 TI - [Alcoholic and nonalcoholic steatohepatitis. Histopathologic and pathogenetic considerations]. AB - Alcoholic (ASH) and nonalcoholic (NASH) steatohepatitis show an almost identical morphology. Since the clinical picture is not characteristic, liver biopsy is still the diagnostic gold standard. ASH and NASH are morphologically characterized by a combination of steatosis, hepatocellular injury (ballooning degeneration, apoptosis, necrosis), perivenular and pericellular fibrosis, and inflammation (mostly neutrophils). A definitive differentiation of ASH and NASH is only possible by exclusion of alcohol abuse. Although NASH comprises a syndrome with a multifactorial etiology, adipositas seems to be the most constant associated causal factor. The pathogenesis of both diseases is still unclear. Clinical evidence and experimental studies suggest an important toxic role of reactive oxygen species (oxidative stress). According to our experience, ballooning of hepatocytes is a constant morphologic feature of ASH and NASH and already present in the early stages of disease. Ballooned cells often (but not always) contain Mallory bodies (alcoholic hyalin), which are irregular cytoplasmic inclusions consisting of keratins and nonkeratin components, including ubiquitin. Ballooning is associated with a disturbance and finally almost disappearance of the keratin-intermediate filament cytoskeleton. In our studies on the pathogenesis of ASH and NASH, we concentrated on these cytoskeletal alterations and Mallory body formation. It could be shown that in the early stages overexpression and hyperphosphorylation of keratins take place. Moreover, the 1:1 ratio of keratin type I (keratin 18) and type II (keratin 8) necessary for the assembly of intermediate filaments is disturbed and the equilibrium shifted toward keratin 8. Thus, the pool of soluble keratin 8 increases. The resulting keratin monomers are sensitive to misfolding and either degraded or aggregated as inclusion bodies. If the proteolytic capacity is impaired (e.g., by inhibition of the proteasomal system) in the chronically stressed cell aggregation prevails,finally leading to Mallory body formation. Convincing evidence exists on the basis of clinical and experimental studies that keratins exert a nonskeletal protective function in simple epithelia (e.g., liver cells). Disturbance of the keratin system may thus significantly contribute to cell damage. PMID- 11766639 TI - [Preneoplasia of the liver. Definition--differential diagnosis--clinical consequences]. AB - The great advances in radiological imaging techniques and their widespread availability have focused attention on hepatic premalignant nodular lesions. The histological differential diagnosis of these nodules can often be difficult, especially in needle biopsy specimens with limited material. Diagnostic considerations differ significantly between livers with and without cirrhosis: In the noncirrhotic liver, the differential diagnosis includes liver cell adenoma, nodular regenerative hyperplasia, and hepatocellular carcinoma. In cirrhosis, dysplastic nodules (low and high grade), dysplasia (large and small cell) as well as hepatocellular carcinoma may occur. The standardization and the uniform use of the nomenclature of these entities are necessary for a better understanding of the biological nature and etiopathology of these lesions. Only a commonly accepted nomenclature makes a comparison of different therapeutic treatment regimens feasible. PMID- 11766640 TI - [Highly differentiated hepatocellular tumors. Concepts, criteria, and differential diagnosis]. AB - Well-differentiated hepatocellular tumors represent a difficult diagnostic problem in hepatopathology with rising clinical impact. The differential diagnosis mainly includes well-differentiated hepatocellular carcinoma (HCC) and its premalignant precursor lesion, the dysplastic nodule (DN), in addition to multiacinar regenerative nodule as well as hepatocellular adenoma (LCA) and focal nodular hyperplasia (FNH). Optimized diagnosis of these lesions is based on exact histomorphological analysis, a close interdisciplinary cooperation as well as good clinical and anamnestic information. Histopathological differential diagnosis requires the search for specific characteristics and detailed analyses of the subtle cytological differences, the histoarchitecture, and also the surrounding nontumorous liver tissue. Special techniques may be helpful in selected cases but currently are of limited importance. PMID- 11766641 TI - [Concomitant occurrence of angiomyolipoma, focal nodular hyperplasia, bile duct adenoma, and cavernous hemangioma in the liver]. AB - The simultaneous occurrence of different hepatic tumors is rare. We present for the first time a concomitant manifestation of an angiomyolipoma, a focal nodular hyperplasia, a bile duct adenoma, and a cavernous hemangioma in a 63-year-old female patient. The largest of the tumors, preoperatively suspected to be hepatocellular carcinoma, was an angiomyolipoma with monotypic epithelioid histology and positive immunoreactivity for HMB-45, actin, desmin, and pancytokeratin. The significance of immunohistochemistry for the differential diagnosis of hepatic neoplasms is emphasized. Finally, a review of the literature with special regard to etiology and pathogenesis of neoplastic liver disease is given, leading to the assumption that the association of four different benign intrahepatic tumors is rather more fortuitous than pathogenetically related, despite the putative similar pathogenesis of focal nodular hyperplasia and hemangioma. PMID- 11766642 TI - [Diffuse hemangiomatosis of the liver and spleen in an adult]. AB - Diffuse hemangiomatoses are extremely rare in adults. The etiology and natural history of the disease are not well understood. A case of diffuse hemangiomatosis of the liver and spleen associated with progressive liver failure, thrombocytopenia, and disturbance of blood coagulation (comparable to Kasabach Merritt syndrome) is presented in a 62-year-old male. We describe the histopathological and immunohistochemical findings and illustrate the morphological aspects of differential diagnosis, distinguishing the disease from other vascular proliferations. PMID- 11766643 TI - [Chronic myeloproliferative disorders. The new WHO classification]. AB - Except for chronic myelogenous leukemia (CML), chronic myeloproliferative disorders (CMPDs) include as main subtypes polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), and essential thrombocythemia (ET). A common finding in CMPDs is a clonal evolution associated with a significantly variable course, which may be complicated by thrombocythemia, (secondary) myelofibrosis, and finally acceleration (unstable phase) that merges into blastic crisis. New therapeutic modalities (chemo- and interferon therapy, bone marrow and stem cell transplantation) which were developed in the last decade and the striking differences in survival amongst the different subtypes warrant not only an unequivocal distinction from reactive and allied disorders, but a clear-cut classification as well. For this reason, a synoptical approach is essential including clinical data and, as a major diagnostic tool, a bone marrow biopsy. This concept finds expression in the new WHO classification, which also includes as rare subtypes chronic neutrophilic leukemia, eosinophilic leukemia, chronic hypereosinophilic syndrome, and finally unclassifiable entities. Histopathology of bone marrow biopsies reveals specific findings, in particular concerning megakaryopoiesis, which are characteristic for the different subtypes. These features facilitate the still controversially discussed differentiation of thrombocythemia that is frequently present, as is the case in initial (prefibrotic) IMF from ET. Moreover, in addition to clinical findings,the associated heterogeneity of bone marrow morphology indicates a stepwise evolution of the disease process and thus exerts a significant impact on survival, i.e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia. PMID- 11766644 TI - [Conservative or operative treatment of humeral head fractures in the elderly?]. AB - The humeral head fracture in the elderly represents an unresolved problem, which is reflected by the variety of existing therapeutic strategies ranging from conservative treatment to humeral head replacement. The main factors influencing the prognostic outcome are the fracture type, age of the patient and biologic criteria such as osteoporosis, blood supply at the fragments, and the degree of soft tissue trauma. For selection of the optimal treatment, the general condition of the patient, additional injuries and chronic diseases have to be respected as much as the patient's compliance and personal demands. According to experimental and clinical findings, for displaced two- and three-part fractures of the elderly patient minimal osteosynthesis and in the future plate osteosynthesis with angular stability should be preferred. For these fracture types, conservative treatment must be included in the therapeutic spectrum. In contrast, displaced four-part fractures and fracture dislocations are indications for primary humeral head replacement. This is explained by the fact that neither conservative treatment nor surgical reconstruction procedures meet the main goal of primary therapy, aiming for early painless mobilization and for timely discharging the elderly patients in their social environment. PMID- 11766645 TI - [Osteosynthesis techniques in proximal humeral fractures]. AB - Although proximal humeral fractures are common injuries, there is no generally accepted strategy as to how unstable and displaced two- to four-part fractures should be managed. Surgical therapy is in a conflicting situation between the requirement for anatomical fracture reduction and stable fixation, on the one hand, and the necessity for minimal intraoperative damage to the soft tissue and arterial vascularization of the humeral head in order to avoid avascular necrosis on the other. Whereas minimally invasive procedures using closed or percutaneous reduction and fixation techniques are advantageous for protection of the arterial blood supply of the proximal humerus, plate fixation provides superior fixation stability. Plate fixation seems to be associated with a reduced risk of avascular necrosis when indirect reduction techniques are used. Poor results in the operative management of humeral head fractures are often seen in association with malunion. There is therefore a tendency towards the use of implants with angular stability in order to reduce the risk for secondary loss of reduction during functional after treatment. Innovative new plates and intramedullary nails that provide superior stability of fixation of the humeral head fragment have been actually introduced into clinical practice. Together with the specific patient and fracture characteristics, the final result of operative management, however, remains mainly related to the knowledge and operative skills of the trauma or orthopaedic surgeon who deals with these proximal humeral fractures. PMID- 11766646 TI - [Indication and technique for shoulder endoprostheses in fractures]. AB - In the treatment of fractures of the humeral head, prosthetic replacement today is accepted as part of the therapeutic repertoire. The indication for this procedure is given if alternative conservative or operative techniques of preserving the humeral head in hemiarthroplasty of the shoulder joint led to universally poor outcomes. The models of endoprostheses that are currently available on the market mainly differ in the stem fixation method and means of securing the tuberosities and rotator cuff. Functional outcome of hemiarthroplasty of the shoulder joint after trauma is less than satisfactory regardless of the type of implant. However, a stable, painless joint is obtained yielding satisfactory subjective patient outcomes. For correct indications for prosthetic replacement of a fractured humeral head the surgeon also has to know the results that can be achieved by other methods in a given situation. PMID- 11766647 TI - [Internal fixation of subcapsular fractures of the femoral neck]. AB - Beside of modern surgical and implant techniques and basic pathophysiological knowledge, internal fixation of subcapsular fractures of the neck of the femur is still known to be connected with a high rate of complications. Implant failure, the typical early complication arising within the first 3 months, non-union, avascular necrosis of the femoral head and late segmental collapse are the typical complications. The type of fracture, timing of operation (emergency operation), quality of reduction and implant positioning have all been shown to predict outcome significantly. However, it is also suggested that further therapeutical interventions like intra-articular pressure decrease by evacuation of hematoma, the kind and technique of reduction, special surgical techniques and postoperative treatment can influence outcome, as well as patient-associated factors like age, degree of osteoporosis, neurological disease, and alcoholism. The superiority of one of the 100 different existing implants have not been proved either by clinical or by biomechanical trials. However, besides screw osteosynthesis, the sliding screw plate and less often sliding nail plate implants are commonly used. Because of the very different biomechanical principles it is of great importance to adhere to the special operative techniques to avoid intraoperative complications that might cause treatment failure. To reduce the frequency of these almost always fatal and in special circumstances lethal complications, we need some more detailed information from good clinical trials and sufficient external quality assurance. PMID- 11766648 TI - [Endoprosthesis in medial femoral neck fractures]. AB - Alloarthroplasty of the hip joint in the elderly has improved significantly the outcome of femoral neck fractures. The indication for a hip replacement is based on the biological age of the patient and the type of fracture. In our hospital in a 5-years period (1996-2000) we treated operatively 305 patients with femoral neck fractures (248 medial, 57 lateral). Of these, 239 patients received a endoprosthesis (190 total hip joint replacements, 49 hemialloarthroplasty). The other 66 patients (most of them younger patients) were treated by osteosynthesis. The complication rate of the endoprosthetic hip replacement was low; five hematoma/seroma and two deep infections had to be treated operatively. In 21 patients (8.79%) we saw hip luxation; 17 could be treated by closed and four by open reduction. Reluxation was found in nine of these 21 patients. Only two patients (both over 80 years old) died between the first 2 postoperative weeks. Eighty percent of the patients were able to walk, half of them alone or with help outside their homes. Fifteen percent of the patients could be mobilized in a wheel chair; only 5% were confined to bed. CONCLUSION: For the treatment of femoral neck fractures in older patients, the cemented hip endoprosthesis is the method of choice. PMID- 11766649 TI - [Techniques of extramedullary osteosynthesis in proximal femoral fractures]. AB - Plate osteosynthesis at the proximal femur is possible for intertrochanteric and subtrochanteric femoral fractures. Common implants are the dynamic hip screw (DHS), the dynamic condylar screw (DCS) and the condylar blade plate. The dynamic hip screw is mainly used in introchanteric femoral fractures, whereas the other two devices are suitable for stabilizing subtrochanteric fractures. Those extramedullary implants compete with several intramedullary nailing systems. Because of less soft tissue compromise the nailing systems have been favored by many surgeons during the last decade. This is particularly true for the subtrochanteric area where intramedullary devices offer higher primary stability, allowing initial full weight bearing. A good indication for the extramedullary technique with a two-hole dynamic hip screw is the stable intertrochanteric fracture with an intact lesser trochanter. The other fracture types of the proximal femur in the intertrochanteric and subtrochanteric area are better treated with intramedullary devices. The remaining indications for the dynamic condylar screw and the condylar blade plate are correction osteotomies and some salvage procedures. PMID- 11766650 TI - [Stabilization in treatment of per- and subtrochanteric fractures of the proximal femur]. AB - The incidence of fractures in the trochanteric region is high in the elderly, and early stabilization is required that allows immediate weight bearing. Older patients with low bone quality, limited compliance and strength, and the inability for partial weight-bearing, benefit from intramedullary stabilization of these fractures. The choice of implant and the operative technique depends on the degree of instability in the individual fracture type. Intertrochanteric fractures are frequently combined with subtrochanteric fracture types. Their treatment is still a challenge because of the high degree of instability. PMID- 11766651 TI - [Statement of the convocation of professors of general/visceral surgical on habilitation]. PMID- 11766652 TI - [The displaced proximal humeral fracture: is there evidence for therapeutic concepts?]. AB - INTRODUCTION: There is no general agreement on the operative treatment of displaced proximal humeral fractures. While T-plate fixation was the method of choice until the end of the 1980s, minimally invasive techniques have been favoured during the past decade. The indication for primary shoulder prosthesis is controversial. The purpose of this report was to evaluate the scientific evidence of current treatment recommendations. METHODS: Relevant articles were retrieved from "Medline" and "Knowledge-Finder" using the combined search strategy for the keywords "proximal humerus" and "fracture". Retrieved articles were evaluated according to the criteria of evidence-based medicine. RESULTS: The analysis retrieved 3 randomized, 4 prospective, and 26 retrospective studies and a number of review articles relevant to the subject. Limitations of most publications were due to small study populations, differences in patient selection and fracture classification as well as measurements of outcome. According to these studies good functional results can be achieved in dislocated two-part fractures treated with minimal osteosynthesis in the elderly and T-plate fixation in younger patients. For three- and four-part fractures minimally invasive techniques seem to be more favourable in the elderly. However, there is some evidence that alternative therapies such as conservative treatment and plating can be successful in defined populations. A general indication for primary implantation of a prosthesis in four-part fractures in the elderly is not supported by the literature. CONCLUSION: We conclude from our analysis that the scientific evidence for treatment recommendations of displaced proximal humeral fractures is still limited. PMID- 11766653 TI - [Minimally invasive screw fixation of the intracapsular femoral neck fracture in elderly patients]. AB - INTRODUCTION: Increasing life expectancy is associated with an increase of geriatric fractures such as intracapsular femoral neck fractures. Their treatment by arthroplasty imposes a significant burden on our health care system. METHODS: In an open clinical study we investigated the complication rate of a less expensive and less invasive, femoral head saving operative procedure. Between June 1997 and June 2000, 205 intracapsular femoral neck fractures of elderly patients (mean age 78.1 +/- 11.8 years) were fixed with cannulated screws. RESULTS: Seventy-seven percent were displaced fractures and 15.6% were impacted Garden I fractures. Reoperation after internal fixation occurred in 38 patients. The most frequent cause of reoperation was secondary arthroplasty due to redisplacement (14x), femoral head necrosis (10x) and non-union (7x). Implant removal (4x), wound hematoma (1x) and femoral head penetration by screws (2x) were other causes for reoperation. CONCLUSION: Less invasive cannulated screw fixation of intracapsular femoral neck fractures should be considered as a treatment option, because it is a smaller and less expensive operation than prosthetic replacement. Adequate reduction and screw placement, however, are a prerequisite for successful outcome. PMID- 11766654 TI - [Transoral atlanto-axial plate fixation in the treatment of a malunited dens fracture and secondary atlanto-axial instability]. AB - INTRODUCTION: A case of a 22-year-old patient with a malunited dens fracture and secondary atlanto-axial instability is presented. The significant narrowing of the spinal canal due to the atlanto-axial instability was associated with anterior myelon compression and neurological deficit. METHODS: A transoral approach with odontoid resection and anterior atlanto-axial plate fixation was performed. With this technique the atlanto-axial subluxation was reduced and the myelon was decompressed. RESULTS: The postoperative course was uneventful. The follow-up showed a complete remission of the neurological deficit and a bony fusion of the atlanto-axial joints. CONCLUSIONS: The presented case illustrates the importance of an accurate initial diagnosis of the degree of instability and the need for short-term follow-up examinations. If atlanto-axial pseudarthrosis or malunion with anterior spinal cord compression occurs, a transoral procedure with odontoid resection and atlanto-axial plate fixation seems to be an excellent salvage procedure. PMID- 11766655 TI - [The frozen shoulder. Arthroscopy, histological findings and transmission electron microscopy imaging]. AB - INTRODUCTION: During a period of 17 months (February 1998 to July 1999) arthroscopy was performed in 172 patients because of pathologic changes of the shoulderjoint. METHODS: From the history and clinical examination, only eleven patients fulfilled the criteria for primary frozen shoulder set up by Lundberg in 1969. Further investigations such as X-ray examination, ultrasonography and MRI scanning showed no changes that could explain the clinical picture of shoulder stiffness. Of the eleven patients with frozen shoulder. additionally in two cases hyperthyroidism, in five cases diabetes type II and in a further five cases a Dupuytren's contracture could be found. Based on the operative procedure, recently published by Habermeyer, Ogilvie and Warner we carried out an arthroscopic arthrolysis of the stiff shoulder. RESULTS: Diagnostic arthroscopy demonstrated synovialitis in the upper and ventral areas of the joint in over 50% of the patients. Interestingly, intraarticular adhesions were not found in any of our patients; in particular, no obliteration of the axillary recess could be seen. Altogether, in seven of the eleven patients with frozen shoulder, a notably contracted biceps tendon was found which obviously applied increased the force on the humeral head, as in corresponding areas cartilage damage could be demonstrated arthroscopically. A significant increase in fibroblast cells next to loose areas of connective tissue could be shown in histological examinations of biopsies of the capsule in the rotatorer interval. We noted thickened vessel walls and an augmentation of the synovial surface, whereas typical inflammation could not be demonstrated in any of the histological specimens. In the transmission-electron microscope examination (TEM) of samples taken from the capsule in the rotatorer interval, structural changes in collagenous tissue were discernible. Typically, a loss of fibril order and a twisting of collagen fibrils were seen. This twirling led to an up to fourfold diameter of the collagenous fibrils, whereby thin, elastin-like filaments could be seen between the thickened bundles of collagen fibrils. CONCLUSION: In stage of the primary frozen shoulder exclusive fibrosis of the joint capsule was found. Electronmicroscopic twists of collagen fibrills were marked. PMID- 11766656 TI - [Problems in osteosynthesis of patella fractures with the AO tension belt and consequences for new implants. The XS nail]. AB - The eccentric ventral AO tension belt system represents the standard therapy of fractures of the patella. This often leads to unsatisfying results. Relating to Klute and Meenen [10] and the results of our own retrospective study, expressed as a percentage, 5-34% (own results 12.4%) have extremely poor treatment outcome, 23-60% (39%) end in deficiencies of bending, and there are 51-79.5% (65.7%) with subjective complaints after patella osteosynthesis. The disadvantages due to the eccentric tension belt position and the impossibility of applying the tension belt directly to the bone surface are abolished with the development of the XS nail. Due to its central position, constant compression of the entire fracture surface is provided. This is valid for all tension-stressed fractures such as those of the patella and olecranon. In synthetic patellae [5] standardized stress testing with changing tension up to 500 Newton was carried out. The XS nail was compared with the AO tension belt osteosynthesis after osteotomy and osteosynthesis in synthetic patellae. The XS nail was superior to the tension belt for all tests and therefore can be applied to all types of fractures where tension stress exists. We repaired the first 15 patella fractures with the XS nail. In 13 of 15 cases, full load of the injured leg was possible (for stairs a plaster splint was used). The experimental patella tests and first clinical results with the XS nail osteosynthesis after patella fracture confirm the new type of osteosynthesis, and functional treatment with loading seems possible. PMID- 11766657 TI - [Timing of soft tissue reconstruction in severe crush injury of the upper extremity]. AB - Complex injuries of the distal forearm and the hand by industrial machines often require extensive reconstructive procedures. Crush injuries with soft tissue damage extending over the limits of visible injury require a special approach. Large soft tissue defects often have to be covered by extensive flap procedures. The optimum point of time for plastic reconstruction is an essential question and represents a controversial issue in the literature. To be able to compare different patient cohorts in the future, we classify crush injuries into five clinically relevant categories. In the course of this review article, three different cases of severe crush injuries of the upper extremity are representatively discussed. Two patients were reconstructed in a secondary procedure, one patient in the acute phase. Definite coverage of soft tissue defects in severe crush injuries should be performed secondarily after 5-7 days since the extent of damage in this special form of trauma can often only be judged after a few days and the reconstruction of bones, vessels and tendons is completed. PMID- 11766658 TI - [Angle- and rotation-stable internal fixation of proximal humerus fractures with the humerus fixator plate. Early clinical experience with a newly developed implant]. AB - INTRODUCTION: The Humerus Fixator Plate is presented as a new implant for angle- and rotation-stable internal fixation for the operative treatment of proximal humerus fractures at the surgical neck. METHODS: In an ongoing two-centre study, 47 patients were treated with the new implant. To date, 31 patients had clinical and radiological postoperative follow-up examinations with a mean interval of 10 months (range: 6-14 months). RESULTS: In 46 patients (97.9%), complete angle and rotational stability was achieved without limiting the range of motion or requiring immobilization. Good pain relief was obtained in 43 patients (91.5 %), and 3 patients (6.4%) showed moderate pain relief following surgery. There was one implant failure. Utilizing the Constant-Raw score (without any correction factors), a mean result of 82.8 points (range: 46-100 points) was ascertained. The majority of the patients (87.1%) achieved "excellent" or "good" clinical results. X-ray analysis revealed no non-union nor humerus head necrosis. In 4 cases (12.9%), protrusion of a humerus head screw was observed which mandated removal of the implant. CONCLUSION: The first clinical investigations of the novel Humerus Fixator Plate are encouraging and provide essential advances in the treatment of unstable proximal humerus fractures. PMID- 11766659 TI - [Long-term results after resection arthroplasty according to Girdlestone for treatment of persisting infections of the hip joint]. AB - INTRODUCTION: Persisting infections of the hip joint are regarded as one of the most feared complications following total hip arthroplasty or failed osteosynthetic treatment of fractures of the proximal femoral part. In these cases resection arthroplasty according to Girdlestone often is the ultimate treatment. METHODS: Twenty-seven patients (11 men and 16 women) who had undergone resection arthroplasty according to Girdlestone could be included in this study. In all cases Girdlestone operations had been performed because of persisting infections of the hip joint. The mean follow-up was 7.1 years. RESULTS: In 22 out of 27 cases (81.5%) eradication of the infection was finally achieved. At the time of re-evaluation 6 patients had no pain, 12 sometimes suffered from moderate pain, 7 from pain during physical activities and 2 patients experienced pain even at rest. At the time of follow-up, 11 patients used a cane, 14 patients needed two canes or crutches and in 2 cases a wheelchair was necessary. The mean shortening of the leg was 5.2 cm (range 3-15 cm). Clinical evaluation using the score according to Merle d'Aubigne and Postel to assess the functional results showed a mean of 6.7 points (range 2-10 points). Of our patients, 59.3 % were satisfied with the functional results obtained. CONCLUSION: In the long run the Girdlestone procedure still seems to be a reasonable salvage operation for persisting deep infections following hip surgery. PMID- 11766660 TI - [Experimental examination for optimized stabilisation of trochanteric femur fractures, intra- or extramedullary implant localisation and influence of femur neck component profile on cut-out risk]. AB - INTRODUCTION: Fractures of the proximal femur are typical injuries of the elderly. Therefore immediate restoration of weight-bearing capacity and prevention of local complications with the need for of secondary surgical procedures are very important. METHODS: In an experimental test the weight bearing capacity under alternating load up to 2,000 N and 4,000 cycles was analysed in the newest implants for extramedullary fixation (the DHS with lateral buttress plate, DHS) and for intramedullary fixation (the gliding nail, GN). If no instability occurred a static maximum load test was performed. To avoid the influence of other variables the tests were performed with sowbone femora with A2, A31, (AO classification) subtrochanteric reversed and subtrochanteric transverse osteotomies. To analyse the influence of long term alternating load and of the biological bone, a pair of cadaver femora were tested with 100,000 cycles of 2,000 N alternating load after GN and DHS osteosynthesis. In a second examination the influence of the profile of the femur neck component on the migration and cut-out risk was tested. Nine head and neck parts of sowbone femora with a A2 osteotomy 1,000 alternating load tests at 1,000 and 1,500 N were performed after GN I beam plate, gamma nail and PFN screw fixation. Additionally, three pairs of cadaver femora were tested with 6,000 cycles from 1,000-3,500 N of alternating load comparing GN vs gamma, GN vs PFN and gamma vs PFN to avoid influence of the biological variability on the ranking. RESULTS: The weight bearing capacity of the GN (4,230-5,557 N) was about 100% higher than that of the DHS (2,465-3,049 N). The total deformation was 1/3 higher for the DHS (17.3 +/- 2.06 mm) than for the GN (10.73 +/- 4,33 mm). After 100,000 alternating load cycles no instability and a total deformation of 13.3 mm was found for the GN, but for the DHS instability occurred after 15,800 cycles. The migration of the I beam GN plate at 1,000 N in sowbone femora was 0.7 mm for the gamma screw 1.69 mm and for the PFN 2 mm but one cut-out was observed. At 1,500 N the difference are even higher, all three PFN showed a cut-out and in two of the three gamma screws rotation of the head and neck around the screw was observed. In the cadaver tests similar differences were found with a migration at least double that of the GN I beam plate for the gamma screw and the PFN double-screw fixation. There was no difference between the gamma and PFN fixation in the cadaver pair test. PMID- 11766661 TI - [Perioperative local instillation of ropivacaine for postoperative pain relief after surgery on extremities]. AB - INTRODUCTION: The relief of postoperative pain remains one of the most important goals for adequate surgical patient care. METHODS: Prospective, randomised, double-blinded study, including 118 patients (67 M;/ 51 F; median age 43 years, min. 18, max. 74). Two groups were formed. In the verum group a wound instillation with ropivacaine was performed, in the control group not. Intensity of pain, demand for analgesics and satisfaction of the patient were evaluated postoperatively. In 10 patients ropivacaine plasma levels were measured. RESULTS: Significant postoperative pain relief and a decrease in analgesic consumption were found on instillation of ropivacaine. Compared to the control group, patients receiving ropivacaine were significantly more satisfied with the postoperative pain management. Potential toxic plasma levels were not found. CONCLUSION: By the presented method, the surgeon actively contributes to a significant reduction in postoperative pain and analgesic consumption. Furthermore, the patient's benefit is reflected by higher satisfaction with the pain management. Complications due to toxic plasma levels are not seen. PMID- 11766662 TI - [Osteogenetic activity of BMP-3-coated titanium specimens of different surface texture at the orthotopic implant bed of giant rabbits]. AB - INTRODUCTION: The successful combination of osteoinductive factors with current materials used in both endoprosthetics and implantology improves bony ingrowth and long-term stability of the chosen implants. The aim of the present experimental animal study was to clarify in what way faster bony integration can be achieved through additional BMP-3-coating of titanium test implants of different surface textures (hydroxy-apatite-coated or corundum-blasted). METHODS: Thirty of 60 cylindrical titanium test implants with a hydroxy-apatite or corundum-blasted surface were coated with 230 microg porcine, high-purified BMP-3 precipitate per implant to check their osteoinductive potential in a bioassay. In each case a BMP-3-coated and an uncoated control-device were implanted with a gap formation of 1 mm into the femoral part of the patellofemoral joint of the right and left leg of 30 adult giant rabbits. Serial saw slices of all explanted specimens were prepared, and the osseous integration of the implant and time dependent bone neoformation were analyzed microscopically and histomorphometrically 14, 35, and 56 days after implantation. RESULTS: Coating of TiAl4V6-test devices with BMP-3 led in both groups after gap implantation to an improved osseointegration, that was histomorphological and histomorphometrical verifiable. Statistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of new formed bone of the BMP-3 coated corundum-blasted or hydroxy-apatite-coated TiAl4V6 test devices compared to the non-coated controls of the same type (P < 0.01). Light microscopy demonstrated osseointegration without connective tissue membrane around the surface of the implants after 2, 5, and 8 weeks. Better osseointegration was achieved in the hydroxy-apatite-coated implants than in the corundum-blasted implants. CONCLUSIONS: Our results indicate that composite metal implants, as used in endoprosthetics and implantology, are suitable carriers for BMP-3 and improved fixation of the implants can be achieved. PMID- 11766663 TI - [Heterotopic replantation after bilateral lower leg amputation]. AB - INTRODUCTION: Replantation is an established procedure in reconstructive surgery. In a bilateral lower leg amputation attempts should be made to rescue at least one extremity, if the patients' vital conditions are stable. PATIENT AND METHOD: We report on a patient who has suffered a bilateral lower leg amputation. Due to the complex injuries the left leg was heterotopically (cross-over) replanted to the right leg. At the left leg an above knee stump was created. In a second operation a soft tissue defect at the replanted extremity was covered by a free microvascular latissimus dorsi muscle flap. In addition, the tibial nerve was reconstructed. Thirteen months later the patient is able to walk with a prosthesis for his left leg and complete weight bearing of the replanted extremity. DISCUSSION: Indication for replantation depends on accompanying injuries and vital functions of the patient. Compared to a simple amputation a lower leg replantation prolongs hospital stay, delays mobilisation of the patient, and increases the necessary secondary procedures. However, after replantation functional outcome is mostly better than with prosthetic fitting, especially if reconstruction of sensation in the weight-bearing area is successful. Thus, in a bilateral amputation movement and stability, as well as quality of life, are improved by a replanted extremity. PMID- 11766664 TI - [Propane-induced tissue damage: burn or freezing injury?]. AB - Tissue damage due to direct contact of liquid propane with the integument is extremely rare. Only five such cases have been described in the literature. We report the case of a girl who sustained a full-thickness skin necrosis of 14.5 % of her body surface area. There is little agreement about the optimal treatment of these injuries in previous reports. The pathophysiological mechanism suggests a freezing injury. The treatment, however, should be analogous to that of third degree burns. PMID- 11766665 TI - [Schilddrusenchirurgie. Gutartige erkrankungen der Schilddruse]. PMID- 11766666 TI - [Comment by the DRG Committee of DGC and BDC on the recommendation of the DIVI Working Group]. PMID- 11766667 TI - [DRG practice]. PMID- 11766668 TI - [Ambulatory surgeon--quo vadis. Status of the surgical specialty group in Thuringen]. PMID- 11766669 TI - [Report on the Baden-Wurttemberg Federal Society Meeting 16 May 2001]. PMID- 11766670 TI - [Organizational effects of work days of various lengths]. PMID- 11766671 TI - [A swine is beating within me. Is the body a thing or a person. The law cannot decide]. PMID- 11766672 TI - ["Innovative Hospital Management" BDC Seminar, Tuttlingen, 25-26 May 2001]. PMID- 11766674 TI - [Diagnostics and treatment of rheumatoid arthritis. Finnish Rheumatological Association]. PMID- 11766673 TI - ["Innovative Hospital Management" BCD Seminar, Tuttlingen 25-26 May 2001]. PMID- 11766675 TI - Risk perception and communication: informed consent. PMID- 11766676 TI - Emergency surgery in the NHS. PMID- 11766677 TI - The rule of three. PMID- 11766679 TI - Interchangeable oxygen and air connectors. PMID- 11766678 TI - Oxygen or air? PMID- 11766680 TI - The intubating Laryngeal Mask Airway as a guide to fibreoscopy. PMID- 11766682 TI - Anaesthetic drug information leaflets - for the patient or for the doctor? PMID- 11766681 TI - The Airway Management Device; is it not similar to the Combitube? PMID- 11766683 TI - Storage of thiopental. PMID- 11766684 TI - Information on codeine. PMID- 11766685 TI - A defect in disposable equipment. PMID- 11766686 TI - Anaesthetic management for a patient with WAGR syndrome. PMID- 11766687 TI - Tackling rare syndromes. PMID- 11766688 TI - Effect of the number of averaged responses in transient evoked otoacoustic emissions on the results of neonatal hearing screening. AB - This study examined the effect of the number of accepted responses in transient evoked otoacoustic emissions on the results of neonatal hearing screening programmes. The ILO88 Otodynamics Analyzer Quickscreen programme was used for all testing, and a three-stage procedure was adopted by averaging 20, 30, and 260 low noise samples in total. The results were recorded after each stage of the testing in those cases in which, after the first 20 accepted responses, the "pass" criteria were met. Under these circumstances, 117 ears were included in the study from a total number of 334 screened ears. It was concluded that 20 averaged quiet responses are adequate for screened newborn babies to pass the test if the conditions of the "pass" criteria are fulfilled at this stage. In the rest of the newborn babies, testing should be continued using a larger number of clicks. For diagnostic and clinical purposes, the full 260 quiet samples must be used since the results indicated statistically better scores in response and reproducibility measures after the 260 averaged responses. PMID- 11766689 TI - Aging and middle ear function in rhesus monkeys (Macaca mulatta). AB - This study provided tympanometric data on rhesus monkeys (Macaca mulatta) and more support for this monkey as a good model for human peripheral auditory function. There have been few published reports concerning middle ear function in rhesus monkeys, and these experiments addressed that need. In the first experiment, peak acoustic admittance (Ytm) and ear-canal volume (Vea) were measured in 17 older adult monkeys and 16 younger adult monkeys. In the second experiment, middle ear resonance frequency was measured in eight younger adult monkeys and four older adult monkeys. Overall, peak Ytm, Vea, and resonance frequency were similar for monkeys and humans. Specifically, peak mean Ytm and mean Vea in monkeys were comparable to those values in human children. There was a trend for older monkeys to have decreased peak Ytm and Vea, but these trends did not reach statistical significance. There was a significant sex effect similar to what has been reported in humans. Male monkeys had larger peak Ytm values and larger Vea values compared with female monkeys regardless of age. Finally, there were no significant age or sex effects on resonance frequency. PMID- 11766690 TI - Audiological performance with cochlear reimplantation from analogue single channel implants to digital multi-channel devices. AB - Cochlear implantation has been performed for almost two decades at the Vienna University Hospital. Until 1994, single-channel implants were used (Ball Electrode, SC6/2SC6, Vienna/Epoxy, Med-E1, Innsbruck, Austria). The development of multi-channel devices (Combi 40/40+), which provide significantly improved speech recognition performance, led to the reimplantation of some patients who had previously received single-channel implants. It was of particular interest to find out if there was a deterioration of the central "learning process" by the reimplantation from the analogue single-channel device to the tonotopic pulsatile multi-channel stimulation. In this study, we attempted to demonstrate that single channel implants have an impact on the neural organisation of the auditory system. Two groups of post-lingually deaf adult patients were tested. Group A had previously received single-channel implants and were reimplanted with the new Combi 40/40+ cochlear implant (Med-E1, Innsbruck, Austria) in the same ear. Group B was implanted only with the Combi 40/40+. Six different speech recognition tests were subsequently performed on all patients, and the two groups performed similarly. Furthermore, it was discovered that group A obtained significant speech recognition improvement (p<0.05) with monosyllabic words and number tests 1 month following reimplantation. PMID- 11766691 TI - Role of the efferent medial olivocochlear system in contralateral masking and binaural interactions: an electrophysiological study in guinea pigs. AB - Contralateral broadband noise (BBN) elevates ipsilateral auditory thresholds (central masking) and reduces the amplitude of ipsilateral brainstem auditory evoked potentials (BAEPs). Binaural interactions are complex psychophysical phenomena, but binaural interaction components are easily extracted from BAEPs to monaural versus binaural click stimulation. However, contralateral, or binaural, acoustical stimulation is known to activate simultaneously the crossed and uncrossed medial olivocochlear (MOC) efferent systems and decrease activity in both cochleas. Particularly, contralateral BBN stimulation suppresses in part ipsilateral peripheral activity. What is the role of such contralaterally induced peripheral suppression in the overall changes in central BAEPs observed during contralateral masking or binaural stimulation? Compound action potentials (CAPs) of the auditory nerve and BAEPs were recorded simultaneously in awake guinea pigs from electrodes chronically implanted on the round window of the cochlea and the surface of the brain. Peripheral and central measures of contralateral masking and binaural interactions were obtained from responses to monaural or binaural clicks, with or without contralateral BBN, recorded before, during, and after the reversible blockade of the MOC function following a single intramuscular injection of gentamicin. Contralateral BBN effectively reduced the amplitudes of CAP and of all BAEP peaks. CAP to ipsilateral click did not, however, change significantly from monaural to binaural click stimulation; still, normal binaural interaction components developed in the BAEPs. When the medial efferent function was blocked by gentamicin, the normal contralateral BBN suppression of CAP and of the earliest BAEP peak was lost; however, the later BAEP peaks were suppressed by contralateral BBN as before gentamicin, and the central binaural interaction components were unchanged. In these experimental conditions, the MOC efferent system seems to play little role in centrally recorded contralateral masking and binaural interactions. PMID- 11766692 TI - Auditory disablements: an update. AB - In 1999, the World Health Organization issued a document (Beta-2 ICIDH-2) that outlines proposed revisions to the original International Classification of Impairments, Disabilities, and Handicaps. The document, issued for trial purposes, is significant in that it redefines the theoretical context in which audiological research into hearing disability has operated since 1980 and will develop in the future. The purpose of this article is threefold. First, it provides an introductory descriptive overview of the primary disablement dimensions outlined in the Beta-2 version of the ICIDH-2 framework. Second, in discussing the implications of the revised framework for audiology, the article highlights particular classification issues that require clarification if the framework is to be applied effectively in audiological research and practice. Third, the article evaluates the revised framework in the context of recent conceptual developments in audiological research and raises a number of issues for further discussion and investigation. The article concludes that the Beta-2 ICIDH-2 represents a significant advance on the original ICIDH classification framework on three counts. First, much of the rationale underpinning the revised framework, particularly its redefinition of the primary disablement dimensions, is consistent with recent conceptual developments in audiological research into hearing disablements. Second, the framework offers specific pointers for the development of current audiological research and practice. One potential line of enquiry focuses attention on specific ICIDH-2 dimensions that are currently under represented in audiological literature, namely, the participation and contextual factors dimensions. Another potential line of enquiry focuses attention on issues pertaining to the measurement of function, specifically the inclusion of "positive" outcome indicators in assessment. Finally, the publication of the revised ICIDH-2 framework offers a standard frame of reference from which to conduct larger debates in the audiological literature about the nature and purpose of audiological rehabilitation and the influence of the ecological perspective on the rehabilitative process. PMID- 11766693 TI - Survey of the perceived benefits and shortcomings of a specialist tinnitus clinic. AB - Questions about the clinical effectiveness of tinnitus services are of considerable interest to health professionals and health care providers alike in view of the chronic nature of tinnitus, the diversity of tinnitus-related problems, and the range of costs of different approaches to the clinical management of tinnitus. This study sought to identify the views of patients with tinnitus, who attended a specialist tinnitus clinic in Wales, about their satisfaction with that service. One hundred and forty-eight patients returned an open-ended mail-out questionnaire that asked them to list the perceived benefits and shortcomings of attendance at the specialist clinic. The respondents were classified as current or very recent attenders (43 per cent) and those who had first attended between 18 to 60 months earlier (57 per cent). Respondents cited an average of 2.8 benefits compared to only 0.8 perceived shortcomings per respondent. Major areas of perceived benefit included technical assistance, in the form of hearing aid or tinnitus masker fitting, and the general therapeutic nature of the consultation(s) with clinic staff. Statistically significant differences were found in some volunteered benefits in relation to gender and patient status as a current or previous attender. More than one-quarter of the respondents (28.4 per cent) stated that there were no shortcomings to their clinic attendance. The main volunteered shortcoming was lack of treatment effectiveness. The study showed that tinnitus clinic attendance resulted in many of the patients' individually expressed complaints being addressed effectively. Further, the study's findings confirmed the effectiveness of the provision of information and counselling as a fundamental form of tinnitus management for a substantial proportion of patients with tinnitus. PMID- 11766694 TI - [Professor Jan Witold Moll (1912-1990): a creator of Poznan thoracosurgery, a pioneer of cardiosurgery in Poland, on the 10th anniversary of his death]. AB - The theme of his work concerns studies on the professional career of Professor Moll and on his pioneering achievement in the fields of thoracosurgery and cardiosurgery. He worked in the Surgical Ward of the Joseph Strus Town Hospital 8/12 Szkolna St. in Poznan. During the period 1945-1958 he performed, in addition to other operations, 804 resections of lung tissue. He was also the author of the first Polish edition of "The techniques of lung tissue resection" (1957). His experience in this field lead him to cardiosurgery and on the 1st of June 1958 he took up the position of Head of the II Clinic of the Medical Academy in Lodz. In 1975 he became Head of the Cardiosurgery Clinic and it was there that he carried out the first heart transplantation in Poland, on the 4th of January 1969, 13 months after Christian Barnard. PMID- 11766695 TI - [An unsuccessful attempt to move the medical faculty in Edinburgh to Poland]. AB - In the years 1945-1947 attempts were made to move the Medical Faculty from Edinburgh to Poland. The main supporter of this idea was, among others, Professor Antoni Jurasz, a leading authority among Polish medical circles in the West. This concept was taken up by the Polish government in Warsaw. Prof. dr Edward Grzegorzewski, the representative of the Department of Education and the person then dealing with the formation of the Doctors' Academy in Gdansk, tried to bring this concept to fruition. These endeavours were unsuccessful. However, the return of staff to Poland, particularly of professors, from the Medical Faculty in Edinburgh was a success. The execution of this project turned out to be unsuccessful when confronted by the political reality existing at that time. PMID- 11766696 TI - [Adam Wrzosek and his contribution to the development of Polish science]. AB - Adam Wrzosek (1875-1965) played an important role in several fields of medicine. He was one of the founders of a branch of medicine referred to as the history of Polish medicine. He was editor - in - chief of the Archiwum Historii Medycyny (Archives of History of Medicine) the main such journal appearing in print. In 1918, when Poland regained her independence, he was one of the most active organizer of higher education and - above all - a co-organizer of the University of Poznan. Adam Wrzosek organizing abilities were most vividly revealed when he became the founder and first dean of the Medical Faculty and holder of the Chair of History and Philosophy of Medicine, University of Poznan. PMID- 11766697 TI - [Professors Edward Lubicz-Niezabitowski and Stefan Dabrowski recorded in the memoirs of Ludwik Jaxa-Bykowski]. AB - Ludwik Jaxa-Bykowski, the educator and anthropologist from Poznan, was prosecuted and sentenced to oblivion for both his scientific and political ideas after the Second World War. He was arrested in 1948 and disappeared soon after being released from prison. Most of his scientific output was destroyed or disappeared during the War and after 1948. I found some of his manuscripts in the archives of the Department of Anthropology in Adam Mickiewicz University of Poznan which were about to be recycled. Jaxa-Bykowski' memories of two professors of medicine who worked in the Medical Department of University of Poznan were found among these materials. PMID- 11766698 TI - [Prof. Morawiecki: the oculist and outstanding expert in immunology, immunopathology and serology]. AB - Jerzy Morawiecki (1910-1997) was a man with versatile interests. Being an assistant of Professor Wladyslaw Szumowski in the Jagiellonian University he published papers devoted to the history of medicine. After getting his medical degree in 1937 he worked in the Public Health Department in Warsaw under the very well known Ludwik Hirszfeld. There he carried out pioneer studies on the blood groups, the very beginning of a new science - immunology which moulded the scientific interests to which he was faithful for the rest of his life. Under the Nazi occupation of Warsaw he managed to send his paper on blood groups to Switzerland where it was published in 1941. Between 1946 and 1992 he published 18 papers in the field of immunology mainly of the eye. He did pioneer work on the precipitation of antigens and antibodies. The phenomenon of precipitation lines in the cornea is quoted in the literature as the "Morawiecki phenomenon" or as "Morawiecki' lines". He presented the original hypothesis of immunotherapy of intravitreal hemorrhages - the method of acceleration of hemorrhage absorption. The use of Anti-RhD antibodies subsequently became the most effective method of intraocular hemorrhages. PMID- 11766699 TI - [Kazimierz Filip Wize as a physician and a medical ethicist]. AB - Kazimierz Filip Wize (1873-1953) was an interesting and unjustly forgotten, physician-philosopher whose lifetime spanned eight decades over the two past centuries. A disciple of Jan Danysz in Paris, he finally chose to become a psychiatrist. His other fields of interests were philosophy and ethics as well as literature, especially poetry, of which he was an excellent translator from the German. This paper discusses K. F. Wize's life and his philosophical and ethical views, with an emphasis on their specificity, in comparison with the ethical concepts of that time. PMID- 11766700 TI - [Professor Olech Szczepski: excellent pediatrician as well as a specialist interested in medical ethics]. AB - Professor Olech Szczepski was born in Poznan in 1914. His life and medical activity were connected with Poznan. Olech Szczepski worked from 1947 until his death in 1980 in departments of clinical sciences in the University of Poznan and afterwards in the Department of Pediatric Disease in Poznan Medical School. Finally, he became a professor in 1967. First of all, he was an excellent pediatrician and for him, pediatrics was an extensive field of medical activity. He published over 200 papers on topics including medical ethics and the history of medicine. Prof. Szczepski was esteemed as a doctor as well as a man. He was therefore asked to give many lectures on those subjects of which he was justly proud. PMID- 11766701 TI - [About the need for research on the Polish herbal by Marcin of Urzedow]. AB - Opinions about the value and significance of the Polish Herbal by Marcin of Urzedow (Cracow, 1595) differ. Some historians claim that this book was progressive in relation to the previously published Polish herbals, others - on the contrary - say that the Polish Herbal did not make a significant contribution towards the pharmacobotanical knowledge of the time. However none of these historians brought sufficient arguments pro or con the exceptional position Marcin's Herbal. The author of the paper therefore carried out an analysis of the contents of the Polish Herbal, as well as a comparison of the results with those of previously published Polish herbals. PMID- 11766702 TI - [How the history of pharmacy should be taught to pharmacy students]. AB - This is a question which by and of every lecturer of the history of pharmacy, especially when there is plenty of information about the subject, and very little "lecture time" available. A lecturer should also remember, that pharmaceutical faculties aim to produce a good expert on medicine, not "an historian of pharmacy". But it is also desirable for pharmacists - experts on medicines - to obtain an elementary body of information about who contributed to shaping the practice of medicine, its variety and ...its kindness. If such aims were achieved - it would be a great score. And if this basic knowledge leads and encourages on independent exploration of the history of pharmacy - we can put it down as due to the success of this first lecturer. PMID- 11766703 TI - [Reflections]. AB - The author remembers the time, when in the gloomy years of Stalin's regime after the II World War, the lectures of the history of medicine were eliminated in the Medical Academies in Poland. A similar thing happened to the history of pharmacy in pharmaceutical faculties, which is why the author is now asking if lectures on the history of pharmacy or medicine were really necessary? After all, many outstanding doctors and pharmacists graduated at that time? And his answer is that it was a great educational mistake. The history of medicine and the history of pharmacy carry humanitarian lessons of great importance to doctors and pharmacists. History demonstrates that they, off all professions should understand the suffering and pain of a sick patient. Knowledge of the history of medicine and the history of pharmacy can only help. PMID- 11766704 TI - [Experience from the teaching of the history of medicine syllabus in the Military Medical Academy]. AB - This paper presents in which the history of medicine syllabus has evolved over the past 30 years. It presents the aspects that are preferred today, the bibliography the students use and the way the course is conducted. The paper also includes the conclusions from many years experience. PMID- 11766705 TI - [Study on testing method of susceptibility to decompression sickness in aerospace]. AB - Objective. To provide related parameters for astronauts. Method. A study of susceptibility to decompression sickness was carried out in 43 subjects in a hypobaric chamber. Result. Incidence of altitude decompression sickness under rest condition was closely related to age, time of oxygen prebreathing, gas bubble formation rates in the venous blood flow returned to heart and some other physiological indexes. Incidence of decompression sickness was significantly higher in subjects aged 30-36 years than in those aged 19-20 years under the same experimental conditions. In the older subjects body-fat, blood cholesterole and noradrenaline in urine during experiment were significantly higher than those in the younger subjects. It also showed that among persons of the same ages, when prebreathing time was longer, the incidence of decompression sickness was significantly lower under the same experimental conditions. Conclusion. It is desirable that the susceptibility to decompression in astronaut be tested with 1 h oxygen prebreathing before exposure to the altitude of 10000 m for 30 min. PMID- 11766706 TI - [Effect of extremely low frequency magnetic field on brain response to selective mental arithmetic under simulated weightlessness]. AB - Objective. To study effects of extremely low frequency magnetic field (ELMF) on brain function state during weightlessness. Method. The brain event-related potentials (ERPs) during a selective mental arithmetic task were compared in 40 normal subjects (20-25 yrs) before and after ELMF (5 Hz) stimulation during simulated weightlessness (head down tilt -10 degrees, HDT). Result. The amplitude of slow positive potentials which were supposed to be related to the mental arithmetic activity decreased significantly especially in 100 min after HDT, but it did not decrease significantly after ELMF stimulation. Conclusion. ELMF stimulation may improve the brain function state during simulated weightlessness. PMID- 11766707 TI - [The combined effect of noise and vibration on intelligibility of Chinese syllables]. AB - Objective. The changes of auditory effect on Chinese single syllables uttered by talker under combined condition of noise and vibration were investigated. Method. The intelligibility tests were made under three conditions (quiet, 0 dB and -6 dB S/N ratios). The utterances were recorded under combined factors of noise and vibration, single factor of noise or vibration, and the control condition. Result. As compared with control group, the decrease of speech intelligibilities in combined factors groups was significant. It also occurred in most cases as compared with the single factors groups. It showed that combined effects played greater roles as S/N decreased in listening environment. As S/N was -6 dB, the intelligibilities were less than 70 percent. Conclusion. The speech production will be changed under noise and vibration, and the changes will deteriorate communication, especially in adverse listening environment. The results have important implications for communication in aerospace and military environments. PMID- 11766708 TI - [Alterations of arterial vasoconstrictor responsiveness in rats during and after tail-suspension]. AB - Objective. To characterize the time course of alterations in vasoconstrictor properties of arteries during simulated weightlessness, and to examine whether these alterations are reversible. Method. The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoconstrictor response were examined in vitro using isolated arterial rings. Result. Compared with that of controls, contractile tension evoked by KCl and phenylephrine (PE) were lower in abdominal aortic, mesenteric and femoral arterial rings from 2 wk tail-suspended rats (P<0.05); after 4 wk tail-suspension, the responses of mesenteric and femoral arterial rings to KCl or PE were further decreased (P<0.05); but contraction responses of arterial rings from 8 wk tail-suspended rats were similar to that of 4 wk simulated microgravity rats. The reversibility of altered arterial vasoreactivity after 4 wk tail-suspension was observed for 5 wk. Vasoreactivity of abdominal aortic rings was recovered after first week of recovery, but it took five weeks that altered vasoreactivity of mesenteric and femoral artery got back to normal. Conclusion. The alterations in constrictor properties of arteries are dependent on both the duration of tail-suspension and the position of artery, the diminished vasoconstrictor properties appear to reach a new steady state after 4 wk tail-suspension, and the changes are reversible. PMID- 11766709 TI - [Changes in lumen diameters of vessels in arteriolar network in rat soleus muscle after simulated weightlessness]. AB - Objective. To elucidate whether simulated weightlessness can induce changes in lumen diameters of vessels in arteriolar networks in hindlimb muscles and whether these changes are reversible. Method. Changes in lumen diameters of the vessels in the arteriolar network in soleus muscle of 4 wk tail-suspended (SUS-4), 1 wk (REC-1) and 5 wk (REC-5) recovered rats were examined and compared with that of control (CON) rats by use of the method of intra-arterial infusion of a carbon suspension. Result. The lumen diameters of the feeding arteries and arcade arterioles, and the transverse arterioles of the order of both V and II in the SUS-4 group were reduced by 31%, 29%, 28%, and 41%, respectively, as compared with that of the CON group (P<0.01). The diameters of these arterioles in REC-1 group were partially restored but remained significantly less than that of the CON group (P<0.05, or P<0.01). In REC-5 group, except for the transverse arterioles of order II, the diameters of all the other arterioles were fully recovered. Conclusion. These findings indicate that a 4 wk simulated weightlessness might induce atrophic changes in the arterioles of the hindlimb muscles. It also suggests that structural changes in arteriolar network might be an important mechanism accounting for postflight orthostatic intolerance. PMID- 11766710 TI - [Physiological analysis of a mathematical model for predicting somatic eigenstates under combined stresses]. AB - Objective. To put a mathematical model for predicting human somatic eigenstates (HS) into practical engineering design of countermeasures against combined stresses (hypoxia, heat, noise and vibration) in an aircraft cabin, and confirm the model from the human physiological viewpoint. Method. Published works on these 4 stresses were employed to verify the main and interactive effects which had been previously proved mathematically. Result. The main effects of 4 stresses and the significant interactive effects of 2 from 4 stresses agreed with the published experiments in single or in the same combination of these stresses. Conclusion. The model is reasonable in human physiological consideration and has been adopted in engineering design. PMID- 11766711 TI - [Counteracting effect of Chinese herbs-compounds on "blood stasis" induced by bed rest]. AB - Objective. To observe the improved effect of syndromes of blood stasis by taking Chinese medicine during bed-rest simulated weightlessness. Method. Ten subjects were randomly divided into two groups: Chinese medicine group and control group. Both of them were exposed to HDBR -6 degrees for a week. The Chinese medicine group took Chinese medicine during the bed rest, and the control group took sugar water. Result. Syndromes of blood stasis of Chinese medicine group had a significant relief. And some physiological parameters, such as blood pressure, pulse graph, and amount of urine, maintained the level of pre-bed rest. While the control group was more severe than the Chinese medicine group in syndromes of blood stasis. Conclusion. Chinese medicine can be a measure in preventing the effect of weightlessness. PMID- 11766712 TI - [Counteracting effect of Chinese herbs on "insufficiency of spleen qi" induced by simulated weightlessness]. AB - Objective. To observe the counteracting effect of a Chinese herb-compound on "insufficiency of spleen qi" induced by simulated weightlessness. Methods. Animal and human experiment were carried out to the Chinese herb-compound (Dangshen, Baizhu, Fuling etc). Result. This compound protected the tail suspended rats from atrophy of spleen, thymus, soleus and gastrocnemius muscles, prevented excessive decrease of body weight effectively; at the same time it relieved the symptoms of the subjects greatly. Conclusion. It demonstrated that the compound decreased the "insufficiency of spleen qi" of both animals and human subjects. PMID- 11766713 TI - [Cardiovascular response to high sustained +Gz stress in dogs]. AB - Objective. To investigate features of electrocardiography (ECG) and arterial pressure in dog during and after +Gz stress. Method. Six anesthetized dogs were catheterized for the measurement of ascending aortic pressure (AP) and common iliac arterial pressure (CIAP). A lead of ECG was monitored continuously. Then, dogs were placed supine in rotatable platform on one arm of an 1.7 m radius centrifuge. The animals were exposed serially to acceleration profiles of up to +7 Gz, consisting of a slow onset to peak acceleration, 90 s peak G, and a rapid decline back to control. A recovery time of at least 20 min was allowed after each acceleration profile. Result. (1) The amplitude of P-wave was influenced by the magnitude of the acceleration (2.3 +/- 0.2 mV at rest vs. 4.5 +/- 0.5 mV at +3 Gz, 4.8 +/- 0.3 mV at +5 Gz and 5.3 +/- 0.7 mV at +7 Gz, respectively P<0.05). (2) It appeared that arterial mean pressure increased and pulse pressure decreased in CIAP during high +Gz stress. (3) AP increased greatly after +Gz stress (17.29 +/- 5.59/11.31 +/- 3.86 kPa at rest vs. 27.53 +/- 6.12/20.62 +/- 1.86 kPa 30s after +7 Gz P<0.01). Conclusion. (1) The change of the amplitude of P-wave reflected the atrial displacement which may be the reason of arrhythmia. (2) The perfusion pressure is an important physiological parameter to the cardiovascular dysfunction during high +Gz stress. (3) Greatly higher AP after +Gz stress could be a feature of vascular exhaustion. PMID- 11766714 TI - [Developments of the theory of skeletal adaptation to mechanical loading]. AB - The primary mechanical function of bone is to provide rigid levers for limbs to act against mechanical loading and gravity, and to remain as light as possible to allow efficient locomotion. There are increasing evidence that mechanical loading is an important, if not the most important, factor influences bone mass and architecture. Many bones are exposed to thousands of repetitive loads every day, which always cause strains. Unusual strain distributions, high strains, and high strain rates seem to be particularly osteogenic. Bone modeling can increase bone strength and mass, bone remodeling can conserve or reduce them, and each can be turned ON or OFF in response to its own threshold range of bone strains. During growth and development, the skeleton optimizes its architecture and strength by (re)modeling to adapt to the largest voluntary loads on bones. The loads come from muscles, not body weight. A new standard of defining osteoporosis might relate bone strength to muscle strength that concerns the osteopenias pathogenesis and its severity, and it would be useful for prevention and cure of osteoporosis. PMID- 11766715 TI - [Ocular counterrolling as an indicator of vestibular otolith function]. AB - Space Motion Sickness (SMS) occurred in the first few days of space flight correlated with the vestibular function. As the main influence of weightlessness in space focused on the otolith receptors. The test of otolith function is of great importance. Although there are a lot of methods to test otolith function, at present ocular counterrolling is the only relative pure indicator of otolith function. It provide a valid method for predicting SMS susceptibility, it has great application prospect in the research of the SMS mechanism and the readaptability of vestibular function after space flight, it also provides great reference in the clinical diagnosis of vestibular problems. PMID- 11766716 TI - Top-performing orthopedic hospitals discharge more patients directly home despite higher acuity. PMID- 11766717 TI - Technology leads to disease management program cost and utilization reductions. PMID- 11766718 TI - Diabetes management program hikes HEDIS scores. PMID- 11766719 TI - Life-long adherence to diet recommended for PKU patients. PMID- 11766728 TI - The use of lymphadenectomy in clinical stage I endometrial adenocarcinoma at a large community hospital. AB - PURPOSE AND MATERIALS AND METHODS: Because of the inaccuracies in clinical staging of endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) in 1988 changed the staging of endometrial cancer to surgical staging consisting of intraoperative findings and histologic evaluation of the specimen. A decade later, 1998, the United States Society of Gynecologic Oncologists published Practice Guidelines for the surgical staging of endometrial cancer. The purpose of this study was to review the use of lymph node sampling and peritoneal washings in 100 consecutive cases of clinical stage I endometrial cancer and compare these results to the Practice Guidelines of the Society of Gynecologic Oncologists. RESULTS: The vast majority of patients (86%) had peritoneal washings and frozen section (69%) of the uterus. However, only slightly more than half (52%) had palpitation of the pelvic and/or para-aortic lymph nodes. Most encouraging and consistent with the Society of Gynecologic Oncologists' Guidelines is that 87% of the patients with histologically more aggressive cancers (grade III or deep myometrial invasion), had lymph node sampling as did 90.5% with more aggressive histologic subtypes. CONCLUSION: Notwithstanding these results, there is still the need in the 21st century for more uniform guidelines for the surgical staging of endometrial cancer. PMID- 11766729 TI - Malignant mixed mesodermal tumor of the ovary treated with a cisplatin-irinotecan combination: case report. PMID- 11766730 TI - Bullous pemphigoid masquerading as acute radiation dermatitis: case report. AB - We report the first case of bullous pemphigoid complicating radiation therapy for vulvar cancer. Shortly after completion of postoperative radiation therapy for a TIN1 vulvar carcinoma, the patient presented with a rash that started within, but continued to extend, well beyond the radiation field. A biopsy of the lesions confirmed the diagnosis of bullous pemphigoid, and she had prompt clinical resolution with systemic tetracycline and steroids. PMID- 11766731 TI - The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer. AB - OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5 year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer. PMID- 11766732 TI - The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment. AB - OBJECTIVE: Little is known on the type of progestin and regimen type in relation to breast cancer risk. We have compared the effect of medroxyprogesterone acetate (MPA) and norethisterone (NET) on the estradiol stimulated proliferation in MCF-7 cells with respect to different regimens used in combined hormone replacement therapy (HRT). DESIGN: To approximate the in vivo conditions in HRT, MCF-7 cultures were pretreated with estradiol followed by estradiol/progestin treatment to represent the sequential combined model and compared with non pretreated cultures followed by estradiol/progestin treatment for the continuous combined model. RESULTS: When using progestins in the continuous combined form with estradiol (10(-10) M) both progestins showed a significant reduction in the estradiol stimulated proliferation of the MCF-7 cells. In the sequential combined model the addition of MPA led to a stronger significant reduction of MCF-7 proliferation but in a narrower concentration range (from 10(-8) to 10(-6) M) compared to the continuous treatment. NET did not show any significant effect on proliferation in the SC model. CONCLUSION: Different regimen types and different progestins do lead to significantly different effects on the proliferation of a breast cancer cell line. These findings might be useful in the elucidation of potential mechanisms involved in the clinical situation. PMID- 11766733 TI - No BRCA1 germline mutation in a family with uterine papillary serous carcinoma: a case report. AB - The purpose of the study was to examine BRCA1 germline mutation and its relationship to BRCA1 expression in two patients, a mother and a daughter, both diagnosed with uterine papillary serous carcinoma (UPSC). DNA was screened for BRCA1 and BRCA2 germline mutations common in the Jewish population (185delAG, 5382insC, and 6174delT) by PCR-based assay and with a protein truncation test (PTT) to detect mutation in exon 11 of BRCA1 and exons 10 and 11 of BRCA2. BRCA1 expression in fixed tumor tissues was assessed by immunocytochemistry (IHC). No germline mutation in either BRCAI or BRCA2 gene was found in the two patients. Both samples showed reduced levels of BRCAI expression. Taken together, these results suggest that undetected or unscreened for germline mutation may be associated with occurrence of this rare tumor type in two members of the same family. Alternatively, an epigenetic mechanism such as BRCA1 promoter hypermethylation may be responsible for reduced expression of BRCA1 in the absence of DNA mutations. PMID- 11766734 TI - Inhibitory effect of ginsenoside-Rb2 on invasiveness of uterine endometrial cancer cells to the basement membrane. AB - Ginsenoside-Rb2 derived from ginseng inhibited invasiveness to the basement membrane of endometrial cancer cell lines Ishikawa. HHUA and HEC-1-A cells. These cells dominantly expressed matrix metalloproteinase (MMP)-2 (gelatinase A) among MMPs by zymography. Ginsenoside-Rb2 suppressed the expression and activity of MMP 2, but did not alter the expression of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in the cells. Therefore, ginsenoside-Rb2 might inhibit invasiveness to the basement membrane via MMP-2 suppression in some endometrial cancers, and can be used as a medicine for inhibition of secondary spreading of uterine endometrial cancers. PMID- 11766735 TI - Is there a real risk in patients with endometrial carcinoma undergoing diagnostic hysteroscopy (HSC)? AB - OBJECTIVE: The penetration of distention medium into the peritoneal cavity as well as directly into the bloodstream via injured endometrial vessels occurs in a great proportion of patients at hysteroscopy (HSC). This may cause potential risk of dissemination of the malignant cells of endometrial cancer patients. To evaluate the real risk of a poorer prognosis of these patients a prospective multicentric study was started in 1998. MATERIAL AND METHODS: Two groups of patients with endometrial carcinoma have been compared. The diagnosis was made in the study group by HSC and targeted biopsy, while in the control group by classical D&C. At the end of the HSC procedure puncture of the cul de sac was performed and the fluid obtained was cytologically examined. In both groups peritoneal lavage was performed at the beginning of the subsequent operation and the collected fluid was again cytologically examined. In the first phase of the study the cytology findings in both groups were compared. In the second phase which is planned for the next five years. the results of follow-up of both groups of patients will be evaluated. RESULTS: The results were evaluated in 134 patients with HSC and in 61 patients with D&C. In the study group a positive finding of malignant cells from the cul de sac was found in four patients (5.3%), a suspect finding in eight patients (10.7%), and a negative finding in 63 patients (84%). In the remaining 59 patients with HSC no peritoneal fluid was obtained. In the fluid from lavage at the beginning of the operation in the same group of HSC patients, a positive finding of malignant cells was found in 12.1%, a suspect finding in 18.2%, and a negative finding in 69.7%. In the control group (after D&C) the fluid from lavage contained malignant cells in eight patients (13.6%), suspect cells in 12 patients (20.3%), and no malignant cells in 39 patients (66.1%). Both groups were comparable for clinical stages of disease. CONCLUSIONS: Our results suggest that HSC does not increase the risk of penetration of tumour cells into the peritoneal cavity more than estimates in D&C. PMID- 11766736 TI - Extragonadal retroperitoneal endodermal sinus tumor in an eight-month-old female infant. AB - We describe a rare case of an extragonadal retroperitoneal endodermal sinus (yolk sac) tumor in the minor pelvis. Radiologic investigation, which included abdominal ultrasound and computed tomography (CT), showed a large soft tissue mass occupying the pelvic cavity. Radionuclide bone scans demonstrated bone metastases. The serum alpha fetoprotein was elevated. Pathologic examination of the surgical specimen revealed extragonadal yolk sac tumor. Immunohistochemically, the tumor was positive for a-feto-protein and cytokeratins. After postoperative combination therapy, follow-up CT showed decreasing tumoral disease, while serum alpha fetoprotein returned to normal. PMID- 11766737 TI - Herbal complex suppresses telomerase activity in chemo-endocrine resistant cancer cell lines. AB - A herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix suppressed cell viability and telomerase activity in hormone refractory and chemo-resistant cancer cell lines, namely poorly differentiated uterine endometrial cancer cell line AN3 CA, adriamycin-resistant breast cancer cell line MCF7/ADR and cisplatin-resistant ovarian cancer cell line A2780. Furthermore, the herbal complex suppressed the expression of the full length of human telomerase reverse transcriptase (hTERT), which is related to telomerase activity. This indicates that the herbal complex can suppress the tumor growth of chemoendocrine resistant cancers, at least in part via suppression of telomerase activity associated with down-regulated hTERT. PMID- 11766738 TI - Ruptured granulosa cell tumor of the left ovary and mature cystic teratoma of the right ovary: a case report of unusual acute abdominal syndrome. AB - Although granulosa cell tumor combined with a dermoid cyst in the same ovary is rarely seen, adult granulosa cell tumor of the ovary with contralateral teratoma has not been reported to date. In this report we present the first case in the English language literature of a ruptured granulosa cell tumor of the left ovary and mature cystic teratoma of the right ovary presenting as acute abdominal syndrome. The patient underwent total abdominal hysterectomy, bilateral ophorectomy, and multiple pelvic lymph node sampling and infracolic omentectomy. She received combined chemotherapy consisting of bleomycin, etoposide. and cisplatin for six cycles. Subsequent follow-up and workups have revealed no evidence of disease. At 19 months after initial diagnosis, she is disease-free. PMID- 11766739 TI - Adjuvant chemotherapy in early stage uterine sarcomas: an open question. AB - Uterine sarcomas are aggressive gynecological cancers even at early stage of disease. The most common histological types are represented by leiomyosarcoma, endometrial stromal sarcoma, and carcinosarcoma. The mainstay of treatment of stage I-II disease is total hysterectomy with bilateral salpingo-oophorectomy. Adjuvant radiotherapy may decrease local recurrence rates without any significant impact on survival. Adjuvant chemotherapy is a logical approach, since distant recurrences are more frequent than local failures. The chemotherapy regimens commonly used in advanced uterine sarcomas are similar to the ones for advanced soft tissue sarcomas, with anthracyclines and ifosfamide as the most active drugs. However, carcinosarcomas respond better to cisplatin-based regimens. It is advisable to design international cooperative randomized trials with the aim of defining the role of adjuvant chemotherapy in the treatment of early stage uterine sarcomas. PMID- 11766740 TI - Mucinous tumors of the ovary: analysis of 38 cases. AB - Ovarian mucinous tumors stem from ovarian surface epithelium and are divided into benign, borderline and malignant. It is difficult to differentiate borderline and malignant mucinous tumors. Thirty-eight cases of ovarian mucinous tumors which were diagnosed at the Pathology Department of Dicle University Medical Faculty were reviewed. Of these, 18 (47.3%), six (15.7%) and 14 (36.8%) were benign, borderline and malignant, respectively. The patients' ages ranged from 18 to 67 (average 44.5) years. Bilaterality was detected in 1/18 (5.5%), 0/6 and 4/14 (28.5%) of benign, borderline and malignant mucinous tumors, respectively. Mean tumor size was 26.4 cm. Microscopically, there was no stratification in the benign tumors. The borderline tumors had papillary infoldings and 2-3 layers of atypical epithelial cells but no invasion of the stroma. Malignant tumors had four or more layers of atypical epithelial cells and stromal invasion. PMID- 11766741 TI - Marginal-zone B-cell lymphoma, extranodal-malt-type: report of three cases. AB - A high proportion of extranodal lymphoid infiltrates are diffuse small lymphocytic proliferations [1, 2] and therefore pose a particularly challenging diagnostic problem [1-4]. Their benign or malignant nature cannot be determined using clinical and radiologic criteria. The application of traditional morphologic criteria (i.e., cytologic maturity and polymorphism favor benignancy, while cytologic atypia and monomorphism favor malignancy) [5, 6], has probably improved diagnostic accuracy. However, these criteria generally have not been helpful in evaluating the large number of lymphoid infiltrates composed of monomorphic collections of small cytologically-mature appearing lymphoid cells [1 4] and, therefore, have not always accurately predicted clinical behavior. Extranodal lymphoid proliferations are also of considerable biologic interest since their pathogenesis and natural history have not been fully elucidated. Localized non-Hodgkin's lymphoma, extranodal-MALT-type. was diagnosed in our Department in three cases: Two arose in the orbit and the third one in the tonsil. The tumors had a typical histologic appearance. The microscopical features and immunohistochemical profile are discussed. PMID- 11766742 TI - Treatment for complex atypical hyperplasia of the endometrium. AB - OBJECTIVE: To clarify the clinical outcome of women with complex atypical hyperplasia of the endometrium who were treated either by hysterectomy or a non surgical treatment with medroxyprogesterone acetate (MPA). STUDY DESIGN: Thirty of the 53 patients with complex atypical hyperplasia of the endometrium were treated by undergoing hysterectomy and 20 were treated with MPA alone as the primary therapy. Their clinical features and outcomes were evaluated. RESULTS: The ages of the 53 patients ranged from 28 to 62 years (mean 46.2). Fifteen (75%) of the 20 patients (8 of 12 with low-dose MPA and 6 of 8 with high-dose MPA) responded initially to MPA therapy. Two of the 12 patients who were treated with low-dose MPA progressed to endometrial adenocarcinoma. Three patients treated with high-dose MPA conceived after treatment having three healthy infants. CONCLUSION: Primary treatment with high-dose MPA is a safe and effective therapy for women with complex atypical hyperplasia of the endometrium who wish to preserve their fertility. PMID- 11766743 TI - Ovarian capillary hemangioma and stromal luteinization: a case study with hormonal receptor evaluation. AB - BACKGROUND: Ovarian hemangiomas are rare tumors, most of them asymptomatic, and of the cavernous type. Six of the reported cases were accompanied by stromal luteinization. There is a debate whether these luteinized cells promote the growth of the vascular lesion or just represent a stromal reaction. CASE: A 71 year-old female was incidentally found to have a small capillary hemangioma in her left ovary, surrounded by a rim of luteinized stromal cells. Immunohistochemical investigation revealed the presence of estrogen and progesterone receptors in the endothelial cells of the lesion. CONCLUSION: Our histological and immunohistochemical findings, as well as data from the literature, support the view that at least some vascular lesions may result from hormonal stimulation. PMID- 11766744 TI - The importance of serum insulin-like growth factor-I level determination in the follow-up of patients with epithelial ovarian cancer. AB - PURPOSE OF INVESTIGATION: The aim of our study was to assess whether serum levels of serum insulin-like growth factor-I (IGF-I) could be used for the follow-up of the patients with epithelial ovarian cancer and to identify whether it was superior to serum CA 125. METHODS: Our study group consisted of 28 patients diagnosed with epithelial ovarian cancer who had initial high serum CA 125 levels and have received chemotherapy following the operation. Preoperatively and before each chemotherapy administration, serum CA 125 and IGF-I levels were measured. RESULTS: The mean value of preoperative serum CA 125 was 364.0 +/- 152.9 U/ml. Serum CA 125 levels decreased with chemotherapy (Spearman rs= - 0.641, p=0.000). The mean preoperative serum IGF-I concentration was 58.04 +/- 52.7 ng/ml, and it showed a slight increase with chemotherapy. (Spearman rs=0.3 18, p=0.001). We observed that there was a weak-moderate negative correlation between the two markers, and when chemotherapy was administered serum CA 125 levels which were initially high started to decrease while serum IGF-I levels showed a mild increase (Spearman rs= - 0.350, p=0.000). CONCLUSION: The measurement of serum IGF-I does not provide any additional benefit in monitoring the response of the disease to chemotherapy. PMID- 11766745 TI - Ovarian metastasis of primary biliary and gallbladder carcinomas. AB - The ovary is a frequent site of metastasis from a wide variety of malignant neoplasias, with the majority originating in the GI tract. The best known tumor of this type is signet ring cell adenocarcinoma (Krukenberg tumor). The gallbladder and bile ducts are rare sources of these metastases. We are reporting two such cases in which the patients presented with no hepatic symptoms and vague gastrointestinal complaints. The gallbladder and bile duct carcinomas were incidental findings during exploratory laparatomy for an ovarian mass. PMID- 11766746 TI - Nongenital metastatic cancers of the ovary: a clinical analysis. AB - OBJECTIVES: The aim of this study was to outline the parameters affecting the extent and type of surgery for metastatic tumors of the ovary. MATERIAL-METHOD: The data of 34 operated patients diagnosed with metastatic tumors of the ovary at the Istanbul University, Medical Faculty Gynecologic Oncology Department between 1991 and 1999 were evaluated retrospectively. The patients were divided into two study groups according to the origin of the tumor: 1. Metastatic tumors of the ovary originating from the organs apart from the gastrointestinal system (MT NonGIS). 2. Metastatic tumors of the ovary originating from the gastrointestinal system (MT-GIS). Survival rates were calculated in months from the time of ovarian surgical intervention to the date of last known data of patient status. Mean survival rates for the noncensored data were calculated by the Kaplan-Meier method and resulting curves were compared by the log-rank procedure. Statistical significance was determined at the level of 0.05. RESULTS: The survival rate for all cases was 24.21 months: the same rate was calculated to be 45.36 months for the MT-nonGIS group while it was 15.8 months for the MT-GIS group. When both groups were compared in terms of survival rates, the difference was significant (p: 0.0025, log rank: 9.14). Overall cumulative survival rates for 9, 14, 24 and 50 months were 61.59%, 50.05%. 41.7% and 11.58%, respectively. It was also found that surgery performed on patients in the MT-GIS group did not alter the survival rate but if peritoneal metastasis was observed during surgery, life expectancy for these cases was significantly less. CONCLUSION: Although the number of patients included in our study was small, it is important because it gives us a clue about the type of surgery that should be performed in GIS-originating metastatic tumors of the ovary. Our study shows that aggressive surgery should be avoided in patients with peritoneal metastasis/spread. PMID- 11766747 TI - Survival and reproductive function after treatment of immature ovarian teratoma. AB - We conducted a clinical and pathologic review of nine patients with immature ovarian teratoma. The histologic grade of the tumor seemed to be a reliable indicator of prognosis. Low stage and low grade immature ovarian teratomas have an excellent prognosis. Platinum-based chemotherapy has been confirmed to be effective in the management of patients with ovarian germ cell tumors. Low grade pure ovarian immature teratoma is a potentially curable disease and a fertility sparing surgical approach is possible. PMID- 11766748 TI - Adenoid cystic carcinoma of the vulva: conservative surgery using a de epithelized rhomboid flap. AB - Adenoid cystic carcinoma of the vulva is a very rare entity manifested by an indolent clinical course, late recurrence and a propensity for perineural and local invasion. A 41-year-old women underwent radical local excision and ipsilateral superficial lymph-node dissection using a de-epithelized rhomboid flap for adenoid cystic carcinoma of the left vulva. On follow-up after two years the patient is alive and well with no evidence of disease. In this report we present the first case of adenoid cystic carcinoma of the vulva using a de epithelized rhomboid flap. PMID- 11766749 TI - Complexes of Li atoms with formaldehyde (LiOCH2) and formaldimine (LiNHCH2): stability via electrostatic and charge transfer interactions. AB - The Li atom adducts of formaldehyde (LiOCH2) and formaldimine (LiNHCH2) are produced in the gas phase by neutralization of the corresponding cations. Subsequent reionization, ca. 0.3 micros later, shows that the nominally hypervalent complexes LiXCH2 (X=O or NH) are stable, residing in potential energy minima. In the time span between the neutralization and reionization events, the LiXCH2 molecules dissociate partly into their constituents, Li + XCH2, the fragmentation extent of LiNHCH2 being more extensive. Ab initio calculations reveal three bound states for both Li atom complexes. Two (states A and B) resemble C-centered radicals carrying an ion pair, Li+*(-)X-CH2*, and can be viewed as lithiated derivatives of the hydroxymethyl (HOCH2*) or aminomethyl (H2NCH2*) radical; the third state (C) represents a conventional, electrostatically bonded Li-X=CH2 complex with an essentially intact X=C double bond and the unpaired electron located at the metal atom. States A and B are bound more strongly than state C for LiOCH2; the opposite is true for LiNHCH2, where C is the most stable arrangement and B only marginally bound. The larger degree of dissociation observed for LiNHCH2 vis a vis LiOCH2 upon neutralization reionization points out that the experiment samples a considerable amount of state B which is barely bound for LiNHCH2. PMID- 11766750 TI - Toward a high-throughput approach to quantitative proteomic analysis: expression dependent protein identification by mass spectrometry. AB - The isotope-coded affinity tag (ICAT) technology enables the concurrent identification and comparative quantitative analysis of proteins present in biological samples such as cell and tissue extracts and biological fluids by mass spectrometry. The initial implementation of this technology was based on microcapillary chromatography coupled on-line with electrospray ionization tandem mass spectrometry. This implementation lacked the ability to select proteins for identification based on their relative abundance and therefore to focus on differentially expressed proteins. In order to improve the sample throughput of this technology, we have developed a two-step approach that is focused on those proteins for which the abundance changes between samples: First, a new software program for the automated quantification of ICAT reagent labeled peptides analyzed by microcapillary electrospray ionization time-of-flight mass spectrometry determines those peptides that differ in their abundance and second, these peptides are identified by tandem mass spectrometry using an electrospray quadrupole time-of flight mass spectrometer and sequence database searching. Results from the application of this approach to the analysis of differentially expressed proteins secreted from nontumorigenic human prostate epithelial cells and metastatic cancerous human prostate epithelial cells are shown. PMID- 11766751 TI - Structure of melittin bound to phospholipid micelles studied using hydrogen deuterium exchange and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. AB - The structure of melittin bound to dodecylphosphocholine (DPC) micelles was investigated using hydrogen-deuterium (H/D) exchange in conjunction with collision induced dissociation (CID) in an rf-only hexapole ion guide with electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS). The deuterium incorporation into backbone amide hydrogens of melittin with or without DPC micelles was analyzed at different time points examining the mass of each fragment ion produced by hexapole CID. When melittin existed alone in aqueous solution, more than 80% of amide hydrogens was exchanged within 10 s, and the deuterium content in each fragment ion showed high values throughout the experiments. When melittin was bound to DPC micelles, the percentage of deuterium incorporation into the fragment decreased remarkably at any time point. It increased little by little as the exchange period prolonged, indicating that some stable structure was formed by the interaction with DPC. The results obtained here were consistent with the previous studies on the helical structure of melittin carried out by NMR and CD analyses. The strategy using H/D exchange and MS analysis might be useful for studying structural changes of peptides and proteins caused by phospholipid micelles. It could also be applied to membrane-bound proteins to characterize their structure. PMID- 11766752 TI - MALDI-FTMS characterization of oligosaccharides labeled with 9-aminofluorene. AB - 9-Aminofluorene (9AmFL) was investigated as an oligosaccharide label. The label was amenable to high UV detectability but did not interfere with mass spectrometric analysis. The 9AmFL label has high molar absorptivity (epsilon = 1.4 x 10(4) L cm(-1) mol(-1) at lambda = 267 nm), is chemically stable, and adds easily in reductive amination to the aldehyde terminus of oligosaccharides. Various linear and branched oligosaccharides were labeled with 9AmFL and the products were purified by chromatography on porous graphitized carbon (PGC). The derivatization reaction gave excellent yields (>95%). Up to 100-fold increase in UV sensitivity at lambda = 206 nm, compared to the corresponding alditol, was observed. Mass spectra were recorded for the labeled compounds. In the presence of sodium dopant, series of Y- and B-fragments were observed. Protonation of the labeled compounds prior to mass spectrometric analysis resulted in simplified spectra (Y-fragments only) and allowed for complete sequence analysis. The retention of the positive charge at the label in the protonated species was consistent with the basicity of the amine. The smallest amount of labeled sugar to be detected by photo-diode array (PDA) was 5 pmol (lambda = 267 nm). PMID- 11766753 TI - Effects of the position of internal histidine residues on the collision-induced fragmentation of triply protonated tryptic peptides. AB - The collision-induced dissociation spectra of a series of synthetic, tryptic peptides that differed by the position of an internal histidine residue were studied. Electrospray ionization of these peptides produced both doubly and triply protonated molecular ions. Collision-induced fragmentation of the triply protonated peptide ions had better efficiency than that of the doubly protonated ions, producing a higher abundance of product ions at lower collision energies. The product ion spectra of these triply protonated ions were dominated by a series of doubly charged y-ions and the amount of sequence information was dependent on the position of the histidine residue. In the peptides where the histidine was located towards the C-terminus of the peptide, a more extensive series of sequence specific product ions was observed. As the position of the histidine residue was moved towards the N-terminus of the peptide, systematically less sequence information was observed. The peptides were subsequently modified with diethylpyrocarbonate to manipulate the product ion spectra. Addition of the ethoxyformyl group to the N-terminus and histidine residue shifted the predominant charge state of the modified peptide to the doubly protonated form. These peptide ions fragmented efficiently, producing product ion spectra that contained more sequence information than could be obtained from the corresponding unmodified peptide. PMID- 11766754 TI - Gas phase hydrogen deuterium exchange reactions of a model peptide: FT-ICR and computational analyses of metal induced conformational mutations. AB - We utilized gas phase hydrogen/deuterium (H/D) exchange reactions and ab initio calculations to investigate the complexation between a model peptide (Arg-Gly Asp[triple bond]RGD) with various alkali metal ions. The peptide conformation is drastically altered upon alkali metal ion complexation. The associated conformational changes depend on both the number and type of complexing alkali metal ions. Sodium has a smaller ionic diameter and prefers a multidentate interaction that involves all three amino acids of the peptide. Conversely, potassium and cesium form different types of complexes with the RGD. The [RGD + 2Cs - H]+ species exhibit the slowest H/D exchange reactivity (reaction rate constant of approximately 6 x 10(-13) cm3molecule(-1)s(-1) for the fastest exchanging labile hydrogen with ND3). The reaction rate constant of the protonated RGD is two orders of magnitude faster than that of the [RGD + 2Cs - H]+. Addition of the first cesium to the RGD reduces the H/D exchange reaction rate constant (i.e., D0) by a factor of seven whereas sodium reduces this value by a factor of thirty. Conversely, addition of the second alkali metal ions has the opposite effect; the rate of D0 disappearance for all [RGD + 2Met - H]+ species (Met[triple bond]Na, K, and Cs) decreases with the alkali metal ion size. PMID- 11766755 TI - Ion trap tandem mass spectrometry study of dexamethasone transformation products on light activated TiO2 surface. AB - The photocatalytic transformation of dexamethasone and the formation of its intermediate compounds have been studied using titanium dioxide as a photocatalyst. The degradation of dexamethasone occurs easily through the formation of several hydroxy derivatives whose characterization has been made by HPLC/MS/MS. Even if both oxidative and reductive processes can be operating, only oxidative products have been identified in air saturated aqueous suspensions. A pattern of reaction pathways accounting for the observed intermediates is proposed. The obtained experimental evidence may be rationalized postulating the existence of a double initial mechanism. A single oxidation step resulting from the attack by one *OH radical leading to the formation of five hydroxy derivatives and a concomitant attack involving two *OH radicals leading to the hydroxylation of the quinoid moiety of the molecule. PMID- 11766756 TI - Variability of calcium binding to EF-hand motifs probed by electrospray ionization mass spectrometry. AB - The modulation of calcium binding by the EF-hand motifs present in a calmodulin (CAM) homologue, a calcium binding protein (CaBP) from Entamoeba histolytica by three external parameters-pH, ligand coordinator EGTA, and fragmentor voltage was investigated by mass spectrometry. Calcium binding follows expected patterns at highly acidic and alkaline pH with the preponderance of the apo and the completely saturated forms, respectively. Surprisingly, additional nonspecific binding is observed near neutral pH. Studies on EGTA chelation and effects of fragmentor voltage showed cooperativity in calcium removal in at least one of the domains. Similar studies on a smaller construct containing the two high affinity carboxy terminal sites revealed interesting differences and provided an estimate of the specificity and tolerance of the EF-hand motifs to calcium binding and removal. PMID- 11766757 TI - Effect of sequence length, sequence frequency, and data acquisition rate on the performance of a Hadamard transform time-of-flight mass spectrometer. AB - Various factors influencing the performance of a Hadamard transform time-of flight mass spectrometer (HT-TOFMS) have been investigated. Using a nitrogen corona discharge to produce an ion stream of N2+, N3+, and N4+, it is found for spectra containing only N4+ that the signal-to-noise ratio (SNR) closely approaches the value calculated from the ion background by assuming that the ion background follows a Poisson distribution. In contrast, for a more intense beam containing N2+, N3+, and N4+, the SNR is less than its theoretical value because of the appearance of discrete spikes in the mass spectrum caused by deviations in the actual modulation sequence from the ideal one. These spikes can be reduced, however, by decreasing the modulation voltage. Under these optimized conditions, the pseudo-random sequence length is varied to understand how it alters SNR, mass resolution, and scan speed. When the length of the pseudo-random sequence is doubled, the SNR increases by the square root of 2 while the time necessary to record a mass spectrum also doubles. Mass resolution can be varied between 500 and 1200 at m/z = 609 as the sequence length, modulation speed (10 MHz, 25 MHz), and acquisition rate (up to 50 MHz) are changed. Scan speeds of 6000 passes per s can be obtained using a sequence containing 4095 elements modulated at 25 MHz. The capability to tailor the HT-TOFMS to increase the scan speed and resolution with a constant 50% duty cycle makes the technique extremely appealing as a mass analyzer for measuring rapid changes in the composition of an ion stream. PMID- 11766758 TI - Controlled ion fragmentation in a 2-D quadrupole ion trap for external ion accumulation in ESI FTICR mass spectrometry. AB - Undesired fragmentation of electrospray generated ions in an rf multipole traps can be problematic in many applications. Of special interest here is ion dissociation in a 2-D quadrupole ion trap external to a Fourier transform ion cyclotron resonance mass spectrometer (FTICR MS) used in proteomic studies. In this work, we identified the experimental parameters that determine the efficiency of ion fragmentation. We have found that under the pressure conditions used in this study there is a specific combination of the radial and axial potential well depths that determines the fragmentation threshold. This combination of rf and dc fields appears to be universal for ions of different mass-to-charge ratios, molecular weights, and charge states. Such universality allows the fragmentation efficiency of the trapped ions in the course of capillary liquid chromatography (LC) separation studied to be controlled and can increase the useful duty cycle and dynamic range of a FTICR mass spectrometer equipped with an external rf only 2-D quadrupole ion trap. PMID- 11766759 TI - Atmospheric pressure ion trapping in a tandem FAIMS-FAIMS coupled to a TOFMS: studies with electrospray generated gramicidin S ions. AB - A tandem FAIMS-FAIMS system for ion trapping at room temperature and atmospheric pressure is described. The first FAIMS device consisted of a side-to-side configuration (sFAIMS) suitable for ion separation, whereas the second FAIMS device was appropriate for ion trapping (tFAIMS). Ions pre-selected by the sFAIMS entered the tFAIMS and were captured by virtual trapping fields at the hemispherical tip of the inner electrode. The use of the sFAIMS, with wider electrode diameters, and consequently better ion separation efficiency than the tFAIMS, lowered the number of background ions captured in the trapping region of tFAIMS, and thus reduced the space charge effects in the trap. This tandem device was coupled to a laboratory built time-of-flight mass spectrometer and was evaluated using the electrospray generated [M + 2H]2+ ion of gramicidin S. The half-time (t1/2) of the exponential decay of the ion cloud in tFAIMS, determined by monitoring the residual intensity of ions extracted from the ion trapping region of tFAIMS after various delay times, was about 2 s. PMID- 11766760 TI - Evidence for ionization-related conformational differences of peptide ions in a quadrupole ion trap. AB - The differences in boundary-activated dissociation (BAD) onsets have been investigated for peptide ions that were generated by two different ionization techniques, nanoflow electrospray ionization (nanoESI) and liquid secondary-ion mass spectrometry (LSIMS). BAD onsets of these ions were determined to compare the relative internal energies of the ions. Protonated peptide ions formed by nanoESI had lower BAD onsets than ions formed by LSIMS. The BAD onsets of peptides derivatized to have a fixed charge on the N-terminus also were lower for those generated by nanoESI than those generated by LSIMS. The BAD onsets of ions formed by nanoESI did not change with the variation of collisional cooling periods after gating ions into the ion trap and after isolating them prior to dissociation, indicating that the ions formed by the two ionization techniques would not adopt the same energy distributions. It is proposed that the ions formed by the two techniques differ in secondary structure, and the LSIMS ions are collisionally cooled to a lower local minimum along the potential energy surface than the nan PMID- 11766762 TI - Diversity of myosin heavy chain expression in satellite cells from mouse soleus and EDL muscles. AB - Postnatal myoblasts, the satellite cells, originating from slow and fast skeletal muscle fibres differentiate and fuse into myotubes expressing different phenotype of myosin heavy chain (MyHC) isoforms. Little is known, however, of factors which establish and maintain this phenotypic diversity. We used immunofluorescent labelling and Western blotting to examine the expression of slow and fast MyHC isoforms in myotubes formed in vitro from satellite cells isolated from mouse fast twitch extensor digitorum longus (EDL) and slow twitch soleus muscles. Satellite cells were cultured in serum-rich growth medium promoting myoblast proliferation until cross-striated and self-contracting myotubes were formed. We report that in both cultures myotubes expressed slow as well as fast MyHC isoforms, but the level of slow MyHC was higher in soleus culture than in EDL culture. Hence, the pattern of expression of slow and fast MyHC was characteristic of the muscle fibre type from which these cells derive. These results support the concept of phenotypic diversity among satellite cells in mature skeletal muscles and suggest that this diversity is generated in vitro irrespectively of serum mitogens. PMID- 11766761 TI - Laser desorption electron attachment time-of-flight mass spectrometry: a new approach to detection of involatile compounds. AB - We report initial results of a new method for obtaining mass spectra of involatile compounds: laser desorption electron attachment time-of-flight mass spectrometry. With this approach, laser desorbed neutral molecules are entrained in a molecular beam and subsequently ionized by low energy electron attachment. Mass analysis is carried out by a linear time-of-flight. We present a description of the apparatus and a number of examples of our early results on: van der Waals condensates of SF6, Fullerenes, derivatized Fullerenes, perfluorinated polyethers, polyphenylethers, and 5-bromouracil. PMID- 11766763 TI - Alterations in the protein pattern of subcellular fractions isolated from Paramecium cells suppressed in phagocytosis. AB - SDS-PAGE and quantitative densitometric analysis revealed alterations in the protein pattern of subcellular fractions (100,000 x g) isolated from Paramecium aurelia (299s axenic) cells suppressed in phagocytosis as compared with the control. Two different agents were used to block phagocytosis: the beta adrenergic antagonist-1-propranolol (200 microM) and inhibitor of calmodulin dependent processes--trifluoperazine (20 microM). More than 40 polypeptides were identified in the cytosolic (soluble) fractions S1 and S2. A considerable decrease in band intensity was found for three polypeptides: by 60% for 87 kDa band, 52% for 75 kDa and 37% for 42 kDa in comparison to the control, when S2 fractions from propranolol-treated cells of equal load were quantified. TFP treatment evoked only a small decrease in the intensity of the same bands: 9%, 10% and 6%, respectively. The 42 kDa band was identified by Western blot analysis and chemiluminiscent detection to be actin. This result suggests that actin may be a primary target of pharmacological agents used in this study to inhibit Paramecium phagocytic activity. PMID- 11766764 TI - Evidence that supramolecular Congo red is the sole ligation form of this dye for L chain lambda derived amyloid proteins. AB - The mechanism of Congo red binding to amyloid protein was studied in order to establish which of two structural dye versions present in water solutions- unimolecular and supramolecular--represent its actual ligation form. Immunoglobulin L chain lambda of amyloidogenic nature, expressed by Congo red binding and easy gel formation, was used as the model amyloid protein. Congo red was coassembled with rhodamine B, designed to be a marker of the Congo red micellar organisation in complexation with protein. The particular suitability of rhodamine B for this role results from significant difference in its binding affinity to Congo red and to protein. It associates readily with Congo red, becoming incorporated into its micellar organisation, but as homogenous dye it shows an almost complete inability to bind to protein. In view of these properties, Congo red was used as a vehicle to draw rhodamine B into complexation with protein, at the same time supplying evidence of its supramolecular ligation form. The results show that both soluble amyloid precursor L chain and the derived gel material attach rhodamine B coassembled with Congo red but not the homogenous rhodamine B. Despite its dynamic, supramolecular character, Congo red participates in complexation with amyloid proteins as an integral ligand unit. PMID- 11766765 TI - Immunolocalization and activity of aromatase in the bank vole testes. AB - A direct approach to identify the cellular source of P450 aromatase in the bank vole testes (seasonally breeding rodents) is the use of immunohistochemistry with a specific antibody that recognizes this enzyme. To confirm the presence of functional aromatase, its activity was measured in microsomal preparations of whole testes and of seminiferous tubules by means of biochemical assay with tritiated androstenedione. The assay was validated using increasing concentrations of both microsomal preparations. Immunoreactive aromatase was found in Leydig cells, Sertoli cells, and germ cells, especially in spermatocytes and spermatids. The aromatase activity was present in microsomal fractions of whole testis and seminiferous tubules. The immunolocalization of P450 aromatase and aromatase activity have been found as photoperiod-dependent. PMID- 11766766 TI - Immunocytochemical observations on the organ distribution of exogenous monomeric and dimerized lysozyme. AB - Using commercial anti-lysozyme antibodies and anti-dimerized lysozyme rabbit serum produced by us we demonstrated by immunohistochemistry, in some organs of rats, the expression of exogenous egg white lysozyme preparations beside the native lysozyme. After oral administration, the egg white lysozyme was detected in intestinal epithelium, proximal and distal tubules of some nephrons, pulmonary alveolar walls and hepatocytes in the 3rd zone of liver acini, whereas native lysozyme was strongly expressed in intestinal and pulmonary macrophages in both the experimental and control animals. However, expression of the dimerized lysozyme released from the intraperitoneally implanted mini-osmotic pumps and detected using specific antisera was evident only on erythrocytes in intestinal blood vessels. It is concluded that the lysozyme preparations administered per os or parenterally are resorbed to blood circulation and distributed among various organs in an active form and maintaining their antigenic specificity. It may speak for their direct anti-inflammatory and immunomodulatory effects in respiratory, urinary, digestive and other systems. PMID- 11766767 TI - Immunolocalization of PTHrP in the submandibular glands of three rodent species. AB - The present study deals with immunohistochemical localization of PTHrP in bank vole, pine vole and white mouse submandibular glands. PTHrP immunoreactivity was observed in epithelial cells of all ductal segments (intercalated, striated, interlobular and main excretory ducts) of the salivary glands in all the three animal species tested. We also found PTHrP expression in myoepithelial cells surrounding the mucous alveoli of submandibular glands in those animals. The reaction was less intense than that found in the epithelial cells of excretory ducts. We occasionally observed a very slight positive reaction for PTHrP in smooth muscle cells of small blood vessels. We also found PTHrP expression in the neurons of ganglion in the submandibular gland. PMID- 11766768 TI - Evidence for a functional role of cholecystokinin receptors in the rat thyroid gland. AB - The aim of the present study was to examine the role of cholecystokinin (CCK) and/or cholecystokinin receptors subtypes (CCK1R and CCK2R) in the regulation of the thyroid gland structure and function. Animals were autopsied after 6 days of treatment with CCK or CCK receptor-specific antagonists (CCK1a--PD 140,548 or CCK2a--PD 135,158) solely or in combination with CCK. Results suggest that CCK exerts a stimulatory effect on follicular thyroid cells manifested by increased epithelium/colloid volume fraction ratio (E/C). Application of selective antagonists of CCK receptor subtypes has demonstrated that CCK acts through the CCK1 receptor subtype at the level of pituitary TSH. The model of endogenous hormone action reveals that thyroid CCK1 is responsible for the thyroid growth. It can be concluded that the physiological activity of CCK1 receptor plays a significant role in a complex interrelationship between TSH, vagal system and CCK1-dependent function of the thyroid gland. PMID- 11766769 TI - Morphological parameters of the angiogenic response in pancreatic ductal adenocarcinoma--correlation with histological grading and clinical data. AB - The aim of this study was to evaluate angiogenesis in tissue of the pancreatic ductal adenocarcinoma and to correlate it with histopathological data such as tumour differentiation, tumour size, lymph node metastasis and patients survival. Tumour samples obtained during surgery from 36 patients were immunostained for the presence of blood vessels with monoclonal antibody against the CD31 molecule. Evaluation of microvasculature was perfomed by counting the microvessel density (MVD) in selected areas under light microscope as well as by computer assisted image analysis (CAIA). In the latter, the following parameters were used for assessment of microvessels: mean number/field, mean area of the vessels, total area/field and total perimeter/field. MVD values obtained under optical microscope and with CAIA were highly correlated. All parameters characterising microvasculature in CAIA also revealed a significant correlation with the histological grading of tumours; generally the less differentiated tumours manifested more extensive vascular network. No significant relationship was found between the tumour size and any of the CAIA parameters. The area of vessels (both total and mean values) revealed a significant, inverse correlation with the incidence of lymph node metastases. The same type of correlation was also found between the mean vessel area and the postoperative survival period. The results show that CAIA of microvessels offers new parameters with some predictive value for the outcome of patients with pancreatic cancer. PMID- 11766770 TI - The involvement of angiotensins in the control of prostatic epithelial cell proliferation in the rat. AB - The effects of captopril (the inhibitor of the angiotensin-converting enzyme) and of angiotensins II and IV (3-8 fragment of angiotensin II) on cell proliferation of the prostatic epithelium was investigated in the rat. The incorporation of bromodeoxyuridine into cell nuclei was used as an index of cell proliferation. It was found that the treatment with captopril resulted in the suppression of prostatic epithelial cell proliferation. The antiproliferative effect of captopril was reversed (at least partially) by a simultaneous treatment with either angiotensin II or angiotensin IV. The effects of angiotensins were not blocked by the administration of losartan--AT1 angiotensin receptor blocker. These findings suggest the involvement of angiotensins in the control of prostatic growth, acting via the receptors different from the AT1-subtype (presumably via AT4 receptors). PMID- 11766771 TI - Back to the future. PMID- 11766772 TI - Progress in clinical neurosciences: the evidence for ALS as a multisystems disorder of limited phenotypic expression. AB - Traditionally, amyotrophic lateral sclerosis (ALS) is considered to be a unique neurodegeneration disorder in which motor neurons are selectively vulnerable to a single disease process. Our current understanding of ALS, however, suggests that this is far too limited an approach. While motor neuron degeneration remains the central component to this process, there is considerable phenotypic variability including broad ranges in survivorship and the presence or absence of cognitive impairment. The number of familial variants of ALS for which unique genetic linkage has been identified is increasing, attesting further to the biological heterogeneity of the disorder. At the cellular level, derangements in cytoskeletal protein and glutamate metabolism, mitochondrial function, and in glial interactions are clearly evident. When considered in this fashion, ALS can be justifiably considered a disorder of multiple biological processes sharing in common the degeneration of motor neurons. PMID- 11766773 TI - Current educational issues in the clinical neurosciences. AB - OBJECTIVE: Canadian training in the clinical neurosciences, neurology and neurosurgery, faces significant challenges. New balances are being set by residents, their associations and the Royal College of Physicians and Surgeons of Canada between clinical service, education and personal time. The nature of hospital-provided medical service has changed significantly over the past decade, impacting importantly on resident training. Finally, future manpower needs are of concern, especially in the field of neurosurgery, where it appears that soon more specialists will be trained than can be absorbed into the Canadian health care system. METHODS: A special symposium on current challenges in clinical neuroscience training was held at the Canadian Congress of Neurological Sciences in June 2000. Representatives from the Canadian Association of Interns and Residents, the Royal College of Physicians and Surgeons of Canada and English and French neurology and neurosurgery training programs made presentations, which are summarized in this report. RESULTS: Residency training has become less service oriented, and this trend will continue. In order to manage the increasingly sophisticated hospital services of neurology and neurosurgery, resident alternatives in the form of physician "moonlighters" or more permanent hospital based clinicians or "hospitalists" will be necessary in order to operate major neuroclinical units. Health authorities and hospitals will need to recognize and assume this responsibility. As clinical experience diminishes during residency training, inevitably so will the concept of the fully competent "generalist" at the end of specialty training. Additional subspecialty training is being increasingly sought by graduates, particularly in neurosurgery. CONCLUSIONS: Training in neurology and neurosurgery, as in all medical specialties, has changed significantly in recent years and continues to change. Programs and hospitals need to adapt to these changes in order to ensure the production of fully qualified specialists in neurology and neurosurgery and the provision of optimal care to patients in clinical teaching units. PMID- 11766774 TI - The epidemiology of infantile spasms. AB - OBJECTIVE: The aim of this study was to estimate population based incidence rates for infantile spasms (IS) and to study our clinical impression that the incidence of IS has recently decreased in the Canadian Provinces of Nova Scotia and Prince Edward Island. METHODS: Birth cohorts from 1978 to 1998, identified through the hospital health records, EEG records and physician computerized databases, were followed for two years for the development of IS. Disease incidence rates were calculated using denominators derived from Statistics Canada's reported annual live birth rates. RESULTS: The inclusion criteria for IS were fulfilled by 75 patients. The overall incidence of IS was 30.7/100,000 live births (95% Cl 24.3, 38.8). Etiologic classification was symptomatic for 51 cases (68%), cryptogenic for 18 (24%), and idiopathic in six children (8%). Although there were more males (N=44) than females (N=31), the incidence rates were similar. There was a marked variability in annual and five-year incidence rates. CONCLUSIONS: Although the clinical characteristics of our patients were similar to other reported IS populations, the instability in IS incidence rates indicates a need for caution in interpreting smaller IS epidemiologic studies. PMID- 11766775 TI - Sumatriptan responsiveness and clinical, psychiatric and psychologic features in migraine patients. AB - OBJECTIVE: To compare sumatriptan responders and nonresponders in a migraine population with regard to a number of clinical, psychiatric and psychologic features. METHODS: Patients were drawn from a referral headache clinic population, and classified as responders or nonresponders. Clinical features were assessed by a written questionnaire. The lifetime prevalence of several psychiatric disorders was determined by the National Institute of Mental Health diagnostic interview schedule and personality factors were measured by the 16 Personality Factors (16PF) Questionnaire. RESULTS: Nonresponders indicated less influence on their migraine by menstrual factors, had a higher lifetime prevalence of generalized anxiety, and showed 16PF scores indicating greater shyness, self-sufficiency and perfectionism. Nonresponders were also more imaginative and less socially outgoing. CONCLUSION: Although they must be interpreted with caution due to small sample size and the multiple comparisons made, our results indicate that there may be differences between sumatriptan responders and nonresponders with regard to a number of clinical, psychiatric and psychologic factors. These results suggest that biological differences exist between the two patient groups which likely account for both the differences in their responses to sumatriptan and in the clinical features noted above. PMID- 11766776 TI - Parent perceptions of the value of Pediatric Neurology Clinic visits. AB - BACKGROUND: There is little data available on the acceptability to parents, of alternate methods of delivering care to their children. This pilot study explored parents' perceptions of conventional clinic visits and their attitudes to potential alternative methods of delivering care. METHODS: Questionnaires were completed by the families of 200 consecutive children before and after a visit to a tertiary-care Pediatric Neurology Clinic in Nova Scotia, Canada. RESULTS: Responses were received from 172 (86%) for the first questionnaire and 138 (69%) for the second. There were 59 new referrals, 76 follow-up visits and 39 were seen because of new concerns. Visiting the clinic resulted in school absenteeism for 85% of the children and lost pay for 19% of the parents. Telephone, video conference or replacement of the physician by a nurse practitioner were acceptable alternate methods of assessment for only 10%. The only factor which was associated with willingness to accept telephone as an assessment modality was an initial opinion that the visit was unnecessary. CONCLUSION: Escalating health care costs and limited specialist availability demand consideration of alternate methods of care delivery. Although adults seem comfortable with care outside the usual clinic setting, there is little data for the pediatric setting. The responses from the parents attending our clinic, indicate that families were happy with services offered in the conventional clinic. In contrast, only 10% found potential alternate methods acceptable. These opinions must be considered in the design of new methods of caring for children. PMID- 11766777 TI - The carbohydrate and caloric content of concomitant medications for children with epilepsy on the ketogenic diet. AB - BACKGROUND: The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population. METHODS: We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet. RESULTS: We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe. CONCLUSION: We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically. PMID- 11766779 TI - Neuroimaging highlight. Superior sagittal sinus thrombosis. PMID- 11766778 TI - Regional accumulation of 14C-zonisamide in rat brain during kainic acid-induced limbic seizures. AB - BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug developed in Japan. Various experimental studies have investigated the effects of ZNS. However, the mechanism of action of ZNS against limbic seizures and secondary generalization is not well known. We studied ictal regional accumulation of ZNS in the rat brain during kainic acid (KA)-induced limbic status epilepticus. METHODS: Fourteen male Wistar rats underwent a stereotactic operation. For recording the electroencephalogram (EEG), electrodes were placed in the left amygdala (LA), left dorsal hippocampus, and over the left sensorimotor cortex. For microinjection, a stainless steel cannula was also inserted into the LA. Seven days after surgery, rats were anesthetized and a catheter was inserted into the femoral vein. The animals were immobilized and allowed to recover from anesthesia for at least two hours. In eight rats, 1.0 microL (1.0 microg) of KA was injected into the LA, and 1.0 microL of phosphate buffer solution was injected into the LA in six control rats. Sixty minutes after injection, 14C-ZNS was administered intravenously, and an autoradiographic study was done. RESULTS: During limbic status epilepticus, only seizures in the sensorimotor cortex were markedly attenuated a few minutes after 14C-ZNS administration. Additionally, high uptake of 14C-ZNS was noted ipsilaterally in the sensorimotor cortex, parietal cortex and thalamus (lateral portion). In control rats, no EEG change was seen, and distribution of 14C-ZNS was rather homogeneous. CONCLUSIONS: These results suggested that ZNS suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex. PMID- 11766780 TI - The role of MRI and nerve root biopsy in the diagnosis of neurosarcoidosis. AB - OBJECTIVES: Neurological involvement occurs in 5-15% of patients with sarcoidosis and isolated "neurosarcoidosis" occurs in less than 1% of all cases. Classical clinical presentations have been described, such as bilateral facial palsy, but often the disease presents insidiously with varied signs and symptoms. We present a patient who required biopsy of a lumbar nerve root for diagnosis of chronic, progressive neurosarcoidosis and review the literature with an emphasis on diagnosis. METHODS: We have reviewed a patient who presented with signs and symptoms related to infiltration of her meninges and nerve roots by sarcoidosis. All pertinent history and physical information was taken from interviews with the patient and review of her chart. Laboratory, radiographic, and pathological investigations are presented. RESULTS AND CONCLUSIONS: A high index of suspicion is required for the diagnosis of neurosarcoidosis. Gadolinium-enhanced MRI is useful but the findings are often nonspecific, and there should be a low threshold for biopsy whenever the diagnosis is considered. PMID- 11766781 TI - Listeria spinal cord abscess responsive to trimethoprim-sulfamethoxazole monotherapy. AB - OBJECTIVE: To describe an alternative antibiotic regimen for the treatment of central nervous system Listeria monocytogenes infection. BACKGROUND: Classical treatment of listeria infections of the brain and spinal cord has included ampicillin in combination with gentamicin and chloramphenicol. Antibiotic resistance to L. monocytogenes is extraordinarily low, and the combined risks of nephrotoxicity, ototoxicity, and agranulocytosis in an already critically ill patient make the potential use of trimethoprim-sulfamethoxazole monotherapy for coverage or treatment of listeria an important alternative. METHODS: Case report. RESULTS: A 58-year-old woman presented with a two-week history of progressive quadriplegia. Gadolinium enhanced MRI showed diffuse edema of the cervical and thoracic spine with ring-enhancing lesions. Cerebrospinal fluid and blood cultures both grew L. monocytogenes. Spinal cord biopsy of the lesion revealed inflammation with necrosis and also grew listeria. Intravenous trimethoprim sulfamethoxazole (8 mg/kg in four divided doses) was administered for six weeks with resultant arrest of neurological symptoms and stabilization of the clinical course. Although the patient was quadraparetic she was able to be discharged to a rehabilitation facility. CONCLUSIONS: Trimethoprim-sulfamethoxazole monotherapy may be a potential alternative option for critically ill patients with central nervous system L. monocytogenes infection. PMID- 11766782 TI - Dissecting hematoma of intracranial internal carotid artery in an 8-year-old girl. AB - BACKGROUND: An 8-year-old girl had a minor fall without head trauma and she collapsed the following day while playing. She was awake but mute with focal neurologic signs when admitted to hospital. Radiologic imaging studies showed a progressive left cerebral infarct with left hemisphere vascular narrowing and beading. She died on the third hospital day. METHODS: Autopsy including exploration of neck vessels and neuropathological examination was performed. Postmortem studies included immunostaining for immunoglobulins and fixed complement. RESULTS: Subtotal subintimal dissections of both proximal supraclinoid internal carotid arteries were found microscopically. On the left, the subintimal dissection extended into the major branches of the left internal carotid artery as dissecting hematomas with a major compromise of the arterial lumina. Specific IgM deposition at the dissection sites was found. A literature review shows that subintimal dissection of the intracranial internal carotid artery or its branches occurs rarely, it is often fatal, and it is present in patients with a mean age of 17.5 years in cases studied pathologically. Trauma and physical exertion are the most common associated factors. CONCLUSIONS: Among the causes of ischemic stroke in young individuals, dissecting hematomas of the intracranial portions of the internal carotid artery system rank low. Few reported cases have identifiable pre-existing pathology. The pathogenesis of dissecting hematomas in this region is reviewed and expanded with speculation regarding relevant developmental, anatomical, flow stress and possibly humoral factors that are involved in the disruption of the arterial elastica and subsequent development and extension of a subintimal hematoma resulting in luminal closure and often death. PMID- 11766783 TI - Transient hemichorea/hemiballismus associated with new onset hyperglycemia. AB - OBJECTIVE: To describe three patients suffering from transient hemichorea/hemiballismus associated with hyperglycemia, review previous reports and propose a possible pathophysiological explanation for this phenomenon. RESULTS: Our original cases and previously reported ones reveal a uniform syndrome: mostly female patients (F/M ratio of 11/2), 50-80 years old, usually with no previous history of diabetes mellitus (9/13), develop choreic or ballistic movements on one side of the body over a period of hours. Serum glucose levels are elevated. In most of the patients, a lowering of the blood sugar level reverses the movement disorder within 24-48 hours. CONCLUSIONS: We believe that the combination of a recent or old striatal lesion (causing increased inhibition of the subthalamic nucleus) and hyperglycemia (causing decreased GABAergic inhibition of the thalamus) may be responsible for the appearance of this unilateral hyperkinetic movement disorder. Undiagnosed diabetes mellitus should always be suspected in patients who develop hemiballistic or hemichoreic movements. When hyperglycemia is detected and corrected, the movement disorder usually resolves within two days and may not require symptomatic therapy with dopamine receptor antagonists. PMID- 11766784 TI - Application of an ecosystem model for aquatic ecological risk assessment of chemicals for a Japanese lake. AB - The Lake Suwa version of the comprehensive aquatic systems model (CASM-SUWA) was developed using field data from Lake Suwa and evaluated to examine the utility of CASM-SUWA for assessing the ecological risk of chemicals for aquatic ecosystems. The calibration of the parameters for the model provided that the established reference model simulation could reproduce complex seasonal biomass behavior of populations that were not significantly different from the general seasonal pattern for the Lake Suwa ecosystem. The sensitivity analyses revealed the potential importance of indirect effects and demonstrated that the parameter values of all the trophic levels were important in determining the biomass of each trophic level in the model. The risk estimation of linear alkylbenzene sulfonates (LAS) demonstrated that the model estimated the risks of direct toxic effects on each population and the indirect ecological effects that propagate through the food-web in the model ecosystem. The CASM-SUWA-derived benchmark levels were approximately one order of magnitude less than the field-derived NOECs in literature. The analyses of the comparison implied that the model could provide a good basis in determining an ecological protective level of a chemical of concern in aquatic ecosystem. This modeling study demonstrated that the model can be used to provide additional information for the decision-making process in the management of the aquatic ecological risk of chemicals. PMID- 11766785 TI - Effects of porous media preparation on bacteria transport through laboratory columns. AB - Bacterial and colloid transport experiments related to environmental systems are typically performed in the laboratory, with sand often used as the porous media. In order to prepare the sand, mechanical sieving is frequently used to tighten the sand grain size distribution. However, mechanical sieving has been reported to provide insufficient repeatability between identical colloidal transport experiments. This work examined the deficiencies of mechanical sieving with respect to bacterial transport through sand columns. It was found that sieving with standard brass sieves (1) contaminates the sand with copper and zinc as a linear function of sieving time and (2) inefficiently sizes sand grains below 300 microm (the largest size examined in this study) due to rapid clogging of the sieves. A procedure was developed that allows utilization of brass sieves for sizing the sand grains and removes the metal contamination introduced from the sieves. Bacterial transport experiments utilizing this column preparation procedure gave repeatable breakthrough curves. Further examination of the effects of these treatments on bacterial transport showed interesting results. First, it was found that the metal contamination did not affect the clean-bed bacterial transport. Second. it was found that variations of the column flushing procedure did not alter the clean-bed breakthrough of the bacteria, but did alter the inter particle blocking. Finally, it was found that the shape of the sand grains (oblong vs. rounded) significantly alters the bacterial transport. with the transport being dominated by the smallest dimension of the oblong grains. PMID- 11766786 TI - Selenium and its redox speciation in rainwater from sites of Valparaiso region in Chile, impacted by mining activities of copper ores. AB - The determination of the total concentration of selenium does not provide sufficient information about its toxicity and its bioavailability. The determination of its chemical forms is the basis for understanding the biogeochemical cycle in terrestrial and aquatic ecosystems and for detecting the species which might be toxic to biota. In this work we describe an analytical procedure to carry out the redox speciation of selenium present at ultratrace levels in rainwater from sites of Valparaiso region in Chile, impacted by mining activities of copper ores. A simple preconcentration step of the rainwater sample on a rotavapor system, in vacuum at low temperature permits the concentration of the different redox selenium species until levels quantifiable by sensitive techniques such as differential pulse cathodic stripping voltammetry or by spectrometric techniques, based on the hydride generation and detection by atomic absorption or atomic fluorescence spectrometry. These techniques coupled to redox chemical reactions allow the redox speciation of selenium. The results show that the open evaporation system can be used to concentrate water samples when the aim of the analysis is the determination of the total selenium concentration. On the contrary, to carry out its redox speciation only the preconcentration performed on rotavapor system, in vacuum can be used. When synthetic solutions containing different redox species of selenium, at ultratrace levels, were slowly evaporated on open system, Se(II) and Se(IV) were oxidized. The optimized procedure was then applied to the selenium determination and its redox speciation in rainwater samples collected in sites impacted by mining activities of copper ores. It was found that the amounts of total selenium in rainwater, as copper, from Puchuncavi valley decrease exponentially with the distance from the source, indicating that these elements in this region arise from the industrial complex Las Ventanas. In the redox speciation of selenium, Se(IV) and Se(VI) were the species found in all rainwater samples analyzed, providing selenium in species which are most favorable for their uptake by the vegetation grown in these soils. PMID- 11766787 TI - Rejection of organic compounds by ultra-low pressure reverse osmosis membrane. AB - The introduction of ultra-low pressure reverse osmosis (ULPRO) membrane has widened the horizon of reverse osmosis (RO) in purification of surface water and wastewater as well as desalination of brackish water. The ULPRO membrane chemistry can provide a high water flux at low operating pressure, while maintaining a very good salt and organics rejection. This paper deals with the investigation on the rejection of low molecular weight organic compounds by ULPRO membrane. Laboratory scale experiments were carried out at a pressure of 3 kg/cm2 with a feed flow rate of 1.20 l/min. The rejection of undissociated organic compounds did not show a close relationship with the feed pH. The percentage removal of undissociated organic compounds increased linearly with the molecular weight as well as with the molecular width. The removal efficiency can be predicted by these relationships. But neither molecular weight nor molecular width can be considered as an absolute factor for rejection. The feed pH also influenced the removal efficiency of dissociated organic compounds. The efficiency decreased linearly with the increase in the dissociation constant. PMID- 11766788 TI - Pathogenic-bacterial water contamination in mountainous catchments. AB - This space-time study of bacteriological response compared the presence of pathogens with indicators contained in surface and groundwater in mountainous regions. A systematic search for bacteria such as Listeria, Salmonella, Campylobacter and Yersinia carried out simultaneously with a search for indicators has shown that these waters can occasionally contain potentially pathogens, though these are generally to be found in small quantities. The most common pathogens found are Campyobacter and Listeria. Salmonella has never been isolated. The presence of pathogens is usually accompanied by the presence of classic indicators of contamination such as Escherichia coli, enterococci and other aerobic bacteria. Exceptions are only to be observed in cases of samples presenting very low numbers of pathogens. Such low pathogen levels have a minimal impact on human health; but we cannot exclude that, during periods affected by specific conditions, higher levels might temporarily occur. Our research has demonstrated that classic indicators can be considered as efficient detectors of pathogens in most cases. When these indicators are used systematically and regularly, the human health hazard can be qualified as low but not negligible. The presence of pathogens, together with their survival capacity, brings the protection measures currently applied to safeguard drinking waters sharply into question. PMID- 11766789 TI - Treatment of anaerobically pre-treated domestic sewage by a rotating biological contactor. AB - The performance of a rotating biological contactor (RBC) for the post-treatment of the effluent of an up-flow anaerobic sludge blanket (UASB) was the subject of this study. Different hydraulic and organic loading rates have been investigated. The removal efficiencies of COD(total), COD(suspended), COD(colloidal) and COD(soluble) increased at a higher hydraulic retention time (HRT) and a lower influent organic loading rate. The results obtained indicated that a two-stage RBC reactor at an HRT of 10 h and an organic loading rate of 6.4g COD m(-2) d(-1) represents an effective post-treatment process. Most COD(suspended) and COD(colloidal) were removed in the first stage while nitrification proceeded in the second stage. The overall nitrification efficiency was 92% at an ammonia loading rate of 1.1 gm(-2) d(-1). Total E. coli removal at HRTs of 10, 5 and 2.5h were 99.5%, 99.0% and 89.0%. respectively. The major part of suspended E. coli ( >4.4 microm) was removed by sedimentation or by adsorption in the biofilm of the first stage of RBC (99.66%). However, E. coli in the colloidal fraction (<4.4 to >0.45 microm) was eliminated in the second stage of RBC (99.78%). A comparison of the performance of a one-stage versus two-stage RBC system, operated at the same total loading rate, revealed an improvement in the effluent quality of the two stage effluent as compared to the one-stage effluent. The two stages RBC were used to examine the effect of hydraulic shock loads on reactor performance in terms of COD, nitrification and E. coli removal. PMID- 11766790 TI - An application of permeable reactive barrier technology to petroleum hydrocarbon contaminated groundwater. AB - A funnel and gate permeable reactive barrier was designed and built to treat groundwater contaminated with dissolved phase toluene. ethyl benzene. and xylene and n-alkanes in the C6-C36 fraction range. Removal efficienicies for the funnel and gate system varied from 63% to 96% for the monocyclic aromatic hydrocarbons. Average removal efficiencies for C6-C9, C10-C14, and C15-C28 fraction ranges were 69.2%, 77.6% and 79.5%. respectively. The lowest average removal efficiencies were 54% for the C29-C36 n-alkane fraction. The overall average removal efficiency for the funnel and gate system towards petroleum hydrocarbons present in the groundwater was 72% during the 10 month period over which the data were collected, and has allowed relevant water quality objectives to be met. PMID- 11766791 TI - A multi-component numerical leach model coupled with a general chemical speciation code. AB - A multi-component numerical leach model (SBLEM) was developed by coupling a general chemical speciation code with a modified Crank-Nicolson algorithm to determine the leaching behavior of contaminants in stabillized/solidified (s/s) wastes. The thermodynamic database of the speciation code was modified using batch leaching data. SBLEM was evaluated by simulating a dynamic leaching test of cement-treated combined bottom and fly ash from a municipal solid waste (MSW) incinerator. Simulations used an input composition prepared from acid neutralization capacity (ANC) test data of the ash. The results show that SBLEM can reasonably predict the dynamic leaching behavior of metals from the cement treated ash when the ANC of the ash and pH-solubility curves of metals are well described. This indicates SBLEM simulations may be able to augment or replace experimental leaching tests that can consume a substantial period of time (> 2 months) and in some cases, provide unreliable results. PMID- 11766792 TI - Multiple factor design for reactive mixture selection for use in reactive walls in mine drainage treatment. AB - Sulfate-reducing reactive walls installed in situ in the path of acid mine drainage contaminated groundwater, present a promising passive treatment technology. However, a rigorous and methodical selection of the most appropriate reactive mixture composition still needs to be investigated. The aim of this study was the selection of the most reactive medium using a multiple factor design and the modeling of the sulfate-reduction rate. Reactivity of 17 mixtures was assessed in batch reactors (in duplicates) using a synthetic AMD. Results indicate that within 41 days, sulfate concentrations decreased from initial concentrations of 2,000-3,200 mg/l to final concentrations of <90 mg/l. Metal removal efficiencies ranged between 51-84% for Ni and 73-93% for Zn. Generated sulfate-reduction rate predictive models which had very satisfactory parameters (R2 = 0.86, F = 62.38 (p-level < 10(-13)) and R2 = 0.90. F = 62.30 (p-level < 10( 13))) identified poultry manure and two other carbon sources as the critical variables for sulfate-reduction rate. PMID- 11766793 TI - Sequential inactivation of Cryptosporidium parvum oocysts with chlorine dioxide followed by free chlorine or monochloramine. AB - The main objective of this study was to assess the effect of temperature (4-30 degrees C) on the inactivation kinetics of Cryptosporidium parvum oocysts with sequential disinfection schemes involving the use of chlorine dioxide as the primary disinfectant and free or combined chlorine as the secondary disinfectant in synthetic water. The synergy previously reported for sequential inactivation of C. parvum oocysts with ozone/free chlorine or ozone/combined chlorine did not occur when chlorine dioxide was used. instead of ozone, as the primary disinfectant within the temperature range (4-30 degrees C) and the pre-treatment levels investigated. Sequential ozone/chlorine dioxide and chlorine dioxide ozone experiments revealed that the lower level or absence of synergy for chlorine dioxide/free chlorine and chlorine dioxide, monochloramine was likely the result of chlorine dioxide reacting with oocyst chemical groups that are mostly different from those reacting with ozone, free chlorine, or monochloramine. The CT concept was found to be valid for the primary inactivation kinetics of C. parvum oocysts with chlorine dioxide, thus allowing the use of the simpler CT approach for the development of C. partum inactivation requirements with chlorine dioxide. General consistency was found between the secondary inactivation kinetics of C. parvum oocysts with free chlorine and monochloramine after chlorine dioxide pretreatment obtained in this study with oocyst viability determined by a modified in vitro excystation method and those reported in the literature for the same sequential disinfection schemes based on an animal infectivity assay. PMID- 11766794 TI - Fluorescence properties of some farm wastes: implications for water quality monitoring. AB - Some farm wastes have been analysed for their fluorescence properties using fluorescence excitation-matrix (EEM) spectroscopy. Farm wastes investigated were silage liquor, pig and cattle slurry, and sheep barn waste. All farm wastes exhibited high intensities of fluorescence that can be attributed to the protein tryptophan. Silage liquor was characterised by a very high fluorescence intensity and an initial tryptophan: fulvic-like fluorescence intensity ratio of >20. Cattle and pig slurries exhibited a lower tryptophan : fulvic-like fluorescence intensity ratio (approximately 2-5) and lower tryptophan fluorescence intensity, and tyrosine fluorescence was also observed. Sheep barn wastes had the lowest tryptophan: fulvic-like fluorescence intensity ratios (approximately 0.5-4.0). Farm waste samples were reanalysed under controlled temperature conditions over a period of 50 days after sampling, to investigate the stability of their fluorescence properties. For silage liquor. tryptophan: fulvic-like fluorescence intensity ratios were observed to decrease with time, and were associated with a decrease in tryptophan fluorescence intensity, suggestive of clostridia breakdown of protein. For slurry samples. tryptophan: fulvic-like fluorescence intensity exhibited a more variable time-evolution, and tryptophan fluorescence intensity increased through time; the more complex fluorescence signal is due to the relatively heterogeneous nature of the slurry. Sheep barn waste samples exhibited more stable tryptophan: fulvic-like fluorescence intensity ratio and tryptophan intensities, suggesting these samples were more stable due to their greater age and decomposition. The ratios of tryptophan: fulvic-like fluorescence intensity observed from the farm wastes investigated are significantly higher than those observed in the majority of river waters, suggesting that farm waste pollution events could leave a signature in river waters due to their distinctively high protein fluorescence intensity. PMID- 11766795 TI - Detection of low concentrations of malachite green and crystal violet in water. AB - A simple procedure for the detection of low concentrations of malachite green and crystal violet in water is presented. The dyes were preconcentrated from 1,000 ml of water samples with magnetic solid phase extraction using magnetic affinity adsorbent (magnetite with immobilized copper phthalocyanine dye). Due to the magnetic properties of the adsorbent the preconcentration process can also be performed in water samples containing suspended solids. After elution of the captured dyes, their presence in eluates was detected spectrophotometrically. Concentrations of both dyes in the range 0.5-1.0 microgl(-1) of water could be reproducibly detected. The dyes can be detected not only in potable water, but also in river ones. PMID- 11766796 TI - State detection and control of overloads in the anaerobic wastewater treatment using fuzzy logic. AB - The two-stage anaerobic wastewater pre-treatment was modelled and controlled. The biological state of the reactors could be predicted using a fuzzy logic system and based upon this, proper control actions were taken automatically in order to avoid an overload. The system was designed to handle very strong fluctuations in the concentration of the substrate and the volumetric loading rate. Hydrogen concentration together with methane concentration, gas production rate. pH and the filling level of the acidification buffer tank were used as input variables for the fuzzy logic system. The manipulated variables were the flow rate from the acidification buffer tank into the methane reactor, the temperature and pH of both reactors, the circulation rate of the fixed bed reactor, back flow from the methane reactor into the acidification, and the control of the feed into the acidification buffer tank. The developed control system was successfully tested on a fully automated lab scale two-stage anaerobic digester. Different types of wastewater from food processing industries were successfully applied. Even a restart of feeding with very high COD concentrations (100 gl(-1) after several days of stand by was handled successfully. Effluent concentrations could be kept low without using TOC, COD or equivalent measurements. PMID- 11766797 TI - On-line titration of volatile fatty acids for the process control of anaerobic digestion plants. AB - The on-line titration of volatile fatty acids (VFA) was found to be a reliable method to measure the substrate (metabolite) concentration without the use of expensive analytical devices. A measurement cell was designed that ensures stable long-term operation, high throughputs and copes with both very low and very high VFA concentrations. Using synthetic textile wastewater, a recalibration of the pH probe was necessary only twice a week. A good reproducibility of the VFA concentrations was determined and standard deviations were below +/- 1% of the measured concentration. Changing salt concentrations of the wastewater in the range of 2.5-150 gl(-1) NaCl did not influence the determined VFA concentration significantly. The method was suitable to control the hydraulic retention time in an acidic phase reactor and to determine the acidification rates of wastewater compounds in batch experiments. PMID- 11766798 TI - Characterization of ozone decomposition in a soil slurry: kinetics and mechanism. AB - A series of soil slurry experiments were performed in a carefully conceived reactor set-up to investigate the characteristics of the catalytic decomposition of ozone on a sand and iron surface. Real time on-line monitoring of ozone in the reaction module was possible using flow injection analysis coupled with a computer-controlled UV detector and data acquisition system. The effects of the soil media and size, ozone dosage, pH and p-CBA as a probe compound were examined at the given experimental conditions. Two apparent phases existed, and ozone instantaneously decomposed within one second in the first phase. These were defined as the instantaneous ozone demand (ID) phase, and the relatively slow decay stage. The interactions of ozone with the soil organic matter (SOM) and metal oxides were attributed mostly to the instantaneous decomposition of ozone. From the probe (p-CBA) experiments, 60-68% of total p-CBA removal occurred during the ID phase. The generation of hydroxyl radicals (OH.) was demonstrated and was closely related with metal oxides as well as SOM. Metal oxides in soil surface were considered to have relatively faster reaction rate with ozone and provide more favorable reactive sites to generate higher amount of OH. than SOM. Even at one-tenth concentration of the sands, a goethite-induced catalytic reaction outfitted the removal rate ofp-CBA among all the soils tested. More than 40% of total p-CBA removal occurred on the soil surface. It was inferred that the radical reaction with the probe compound seemed to take place not only on the soil surface but also in the solid-liquid interface. Ozone decomposition and the reaction between OH. and p-CBA appeared to be independent of any change in pH. PMID- 11766799 TI - Real-time control of an immobilized-cell reactor for wastewater treatment using ORP. AB - The performance of an immobilized-cell reactor for simultaneous carbon nitrogen removal in synthetic wastewater with an intermittent aeration (IA) process under real-time control of oxygen supply was investigated. The oxidation-reduction potential (ORP) was monitored during operation. The ORP-time profile showed distinctive turning points. which directly correlated with the changes in the system chemistry and biological activity. The reactor was conducted by cyclic fixed-time aeration nonaeration operation at the beginning, followed by real-time control technology using ORP setpoint. A moving window along the slope of the ORP curve was employed to search for the nitrate breakpoint of the aeration cycle. Once the breakpoint was found, the reactor was aerated for a fixed period. The treatment process could effectively avoid the anoxic fermentation state under the real-time control. The cycle time was reduced around 30%. The duration of aeration period was found to be optimum at 3 h under the consideration of the removal efficiencies of COD and total nitrogen. The real-time control system not only exhibited a better nitrogen removal efficiency than the fixed-time control operation, but it also showed a stable effluent quality during the change of HRT from 3 to 8 h. Good operation stability was demonstrated even when a very high disturbance of the influent loading occurred. PMID- 11766800 TI - Estimation of endotoxin-like substances in deep seawater by using bioassay. AB - Deep seawater has recently been under trial as a fundamental material for mineral water, food, face lotion and an efficacious reagent for the cure of atopic dermatitis in Japan. However, little is known about the biologically effective substances, including toxic compounds in deep seawater. In this study, we investigated the effects of deep seawater on the function of murine macrophages in vitro, and examined the endotoxin-like substances in seawater. Mitochondrial activity and NO production in macrophage cells cultured with stimulants were enhanced in a depth dependent manner by pretreatment with deep seawater. In addition, fractions from deep seawater, enriched by hydrophobic column chromatography, activated the macrophage cells much more than the corresponding fractions from surface seawater. Furthermore, the effects of the fractions on macrophage cells remained significant, even with the addition of polymyxin B. which is a specific inhibitor of endotoxins. These results indicate that endotoxins and unknown substances, which affect macrophage functions, exist in a depth dependent manner in seawater. PMID- 11766801 TI - Detection of infectious enteroviruses and adenoviruses in tap water in urban areas in Korea. AB - We investigated the viral contamination of tap water at 11 urban sites in Korea between 1997 and 1998 over a period of 11 months. A total of 23 tap water samples were examined for infectious enteroviruses and adenoviruses by a cell culture technique followed by polymerase chain reaction (PCR) amplification. To identify the recovered viruses, sequence analysis of PCR products was performed. Infectious enteroviruses and adenoviruses were detected in 11 (47.8%) and 9 (39.1%) of the samples, respectively. Both enteroviruses and adenoviruses were detected in five samples (21.7%). The level of viral contamination was quite high, ranging from 2 x 10(-3) to 2.9 x 10(-2) Most Probable Number of Infectious Unit L(-1), far above the recommended virus level in drinking water set by the US EPA. Poliovirus type I derived from vaccine was frequently detected and the remainder comprised coxsackievirus B type or echovirus type 6, which were causative agents of aseptic meningitis in Korea in 1997 and 1998, respectively. Several types of adenovirus were detected in tap water samples and some water samples were found to contain adenoviruses which were closely related to enteric adenovirus types 40 and 41. PMID- 11766802 TI - Genotoxic response of Austrian groundwater samples treated under standardized UV (254 nm)--disinfection conditions in a combination of three different bioassays. AB - Ground water samples from different geographic areas in Austria, with different amounts of natural and anthropogenic organic compounds were treated with a standardized low pressure UV (254 nm)-irradiation laboratory flow-through system (UV fluence: 800 J/m2). The genotoxic activities of the water samples before and after the UV disinfection were investigated using a combination of three different bioassays which complement each other with regard to their sensitivity detecting different genotoxins. The test battery comprises the Salmonella/microsome assay (Ames test with TA98. TA 100 and TA 102, with and without S9 mix) and two micronucleus tests with the plant Tradescantia (clone #4430) and with primary rat hepatocytes. Overall, the tested Austrian groundwater samples used for human consumption caused only weak genotoxic activities compared to drinking water samples reported from other countries under similar experimental conditions. With the exception of one weak positive result in the Ames test (only in strain TA98 without S9 mix) with an induction factor of 1.9) all samples after UV disinfection were devoid of additional mutagenic and clastogenic activities compared to the samples before UV disinfection. PMID- 11766803 TI - A mathematical model of a high sulphate wastewater anaerobic treatment system. AB - As an aid to the design and operation of anaerobic digesters treating high sulphate waste waters, a mathematical model describing this treatment process has been developed. Apart from sulphate reduction, the model includes those reactions which occur either prior to sulphate reduction or in competition with it. These include, hydrolysis of solid substrates, acidogenesis. beta oxidation of long chain fatty acids, acetogenesis and methanogenesis. By incorporating terms for these reactions the model is able to simulate sulphate reduction using a wide range of carbon sources. Acid/base equilibrium chemistry is included in order to predict the pH and unionized component concentrations, needed for calculating inhibition. An activity based model is used, with the activity coefficients calculated using Debye-Huckle theory. The mass transfer rates of hydrogen, methane, carbon dioxide and hydrogen sulphide from the liquid to the vapour phase are also included. A number of different reactor types may be simulated, including a dynamic batch. steady state CSTR and dynamic CSTR. By separating the hydraulic and solids residence times, high rate reactors such as UASB and packed bed reactors may also be simulated. The model has been used to successfully predict the dynamic and steady state behaviour of a number of different reactor types, utilizing both simple and complex carbon sources. PMID- 11766804 TI - Investigations into the environmental fate and effects of iopromide (ultravist), a widely used iodinated X-ray contrast medium. AB - lodinated X-ray contrast media are pharmaceuticals which are biologically inert and metabolically stable during their passage through the body and are excreted almost completely within a day into waste water. They are not readily biodegradable. However, in a test system simulating sewage treatment, we were able to show that the model compound iopromide (N,N'-bis(2,3-dihydroxypropyl) 2,4,6-triiodo-5-methoxyacetylamino-N-methyliso-phthalamide) was amenable to primary degradation. The resulting degradation product (5-amino-N'N'-bis(2,3 dihydroxypropyl)-2,4,6-triiodo-N-methyliso-phthalamide) showed a faster photolysis than the parent compound. Additionally this product was further degraded in a test system simulating surface water conditions. Short-term toxicity of the primary degradation product was low, i.e. no effects on any of various aquatic species could be found even at concentrations of 1 gl(-1). Additionally no chronic toxicity of the degradation product was observed in an early-life stage test with zebrafish at the highest tested concentration of 100mgl(-1). Based on the results from model systems a degradation pathway for iopromide is postulated. Though further work showing the transferability of the laboratory results to environmental conditions is necessary the presently available information on the environmental fate and effects of iopromide and its degradation products do not provide evidence of a risk for aquatic life caused by the introduction of this contrast medium into waste water. PMID- 11766805 TI - Survival and leaching of fecal bacteria after slurry spreading on mountain hay meadows: consequences for the management of water contamination risk. AB - The aim of this work is to achieve a better understanding of the behavior of fecal coliform populations on the vegetation and in the soil after slurry spreading in environmental conditions, typical of vegetative growth period in mountain hay meadows. Changes in fecal coliform populations on the vegetation and in the soil were monitored in situ for 3 months after slurry spreading on 9 plots. The variations found in populations are related to the agricultural, soil. and climatic characteristics of plots and to the moisture regime of soils. These observations are compared with laboratory experiments on undisturbed soil microcosms. In absence of water flux, survival durations recorded in the laboratory and in the field are of the same order of magnitude. The data enable us to pinpoint the influence of various factors affecting the decline and transfer of fecal bacteria in the plant-soil system and consequently to discuss the risk management of water contamination by agriculture. PMID- 11766806 TI - Removal of ammoniacal nitrogen from landfill leachate by irrigation onto vegetated treatment planes. AB - Leachate is a contaminated liquor resulting from the disposal of solid and liquid wastes at landfill sites that must be treated before discharge. Vegetated leachate treatment planes have been used at landfill sites in the UK but have received little scientific attention. This paper describes studies of model leachate treatment planes with a focus on the removal of ammoniacal nitrogen (NH3 N). Small-scale and field-scale experimental treatment planes were constructed. filled with clay loam soil and vegetated with grass (Agrostis stolonifera). Landfill leachate was applied at hydraulic loading rates ranging from 17 217l/m2/d. An exponential relationship was used to characterise the pattern of NH3-N removal. No relationship was observed between the hydraulic loading rate and the NH3-N removal rate constants (R2 = 0.0039). The daily specific NH3-N mass removal rate was found to be linearly related to the NH3-N concentration at the start of that day of treatment (R2 = 0.35). Possible causes of variation in the rate of NH3-N removal between experiments are discussed. A simple inorganic nitrogen balance indicated that the mass of N-H3-N and NO2-N removed was not accounted for by NO3-N production. Explanations for this apparent nitrogen deficit are discussed. PMID- 11766807 TI - Solubilization of polycyclic aromatic hydrocarbons by perfluorinated surfactant micelles. AB - Due to their chemical and thermal stability, perfluorinated surfactants (PFSs) are promising materials for the development of novel environmental remediation applications. This stability also leads to the persistence of PFS in the environment; therefore, their properties and behavior should be well understood. This study focused on polycyclic aromatic hydrocarbon (PAH) and PFS interactions, particularly the solubilization of PAHs by PFS micelles. Naphthalene. phenanthrene, and pyrene were selected as representative PAHs and an anionic PFS, ammonium perfluorooctanoate (APFO) was used. Critical micelle concentration (CMC) values of APFO measured by surface tension, fluorescence probe, and solubility enhancement methods fell in the range of 20-30 mM at 22 +/- 1 degrees C. Apparent solubilities of molecular oxygen and PAHs in APFO micellar solutions depended linearly on the APFO concentration. Molar solubilization ratio (MSR) values were determined to be 9.50 x 10(-4), 4.17 x 10(-3), 2.31 x 10(-4), and 4.09 x 10(-5) and mole fraction micellar partition coefficient (Kmic) values were found to be 1.89 x 10(2), 9.50 x 10(2), 2.12 x 10(3), and 3.79 x 10(3) for oxygen, naphthalene, phenanthrene, and pyrene, respectively at 22 +/- 1 degrees C. log Kmic values for three PAHs were shown to be linearly correlated with the log values of octanol-water partition coefficients (log Kow). PMID- 11766808 TI - PAH degradation by UV/H2O2 in perfluorinated surfactant solutions. AB - Polycyclic aromatic hydrocarbons (PAHs) solubilized in perfluorinated surfactant (PFS) solutions were degraded by direct photolysis and UV/H2O2 process. The subsequent recovery and reuse of these surfactant solutions were also demonstrated. Phenanthrene and pyrene were selected as representative PAHs and an anionic PFS: ammonium perfluorooctanoate (APFO) was used. In our experiments, micellar APFO solutions retarded the phenanthrene photolysis and enhanced the pyrene photolysis. The results indicate that the photochemical reactivity of compound in micelles is strongly dependent on specific properties of the solubilizate, possibly due to the different excited state behaviors of compound. UV/H2O2 process exhibits a greatly enhanced rate of PAH photolysis in both water and APFO compared to direct photolysis. indicating that hydroxyl radicals may be generated or penetrated at the sites of PAHs solubilized in the micelles. Additionally. a smaller rate enhancement by UV/H2O2 in micelles than in water suggests that micelles provide some degree of protection from hydroxyl radical attack. The possibility of recovery and reuse of PFS has been demonstrated by measuring the solubilizing capacity of APFO after direct photolysis and UV/H2O2 process. Overall, this study demonstrates UV/H2O2 process can be an effective treatment method for not only PAH degradation but also surfactant recovery and reuse. PMID- 11766809 TI - Concentration and loading of pesticide residues in Lake Biwa basin (Japan). AB - The concentrations and loading rates of pesticides used in paddy fields were investigated over a period of 5 years in the Seta River, which is the only natural outlet of Lake Biwa. The lake's water catchment area is 3,174 km2, 20% of which contains paddy fields. Water samples were also collected in six rivers flowing into the lake in order to compare the contamination level and concentration profile. The pesticides analyzed were four herbicides (molinate, simetryn, oxadiazon, and thiobencarb), one fungicide (isoprothiolane), and two insecticides (diazinon and fenitrothion). Molinate, simetryn, oxadiazon and isoprothiolane were found at the higher frequencies with maximum concentrations of 1.1, 0.4, 0.1 and 0.5 microg,/l in the effluent river, one or two order of magnitude higher than that of effluent in influent rivers. These peak concentrations were observed during the application period in influent rivers and two or three weeks after that in effluent river. The frequency of occurrence of thiobencarb, diazinon, and fenitrothion was relatively low and their maximum concentrations in the effluent remained below 0.1 microg/l. The decrease of molinate, simetryn and oxadiazon concentrations in the effluent river were approximated by two straight lines plotted on semilogarithmic scale. Increased loading was induced by intense rainfall, which took place during the application period. Simetryn and isoprothiolane persisted in relatively high concentrations through the year were also influenced on its loading by the heavy rainfall in the following months. The percentages of the total amount of pesticides released through Lake Biwa to the basin in downstream were estimated to be 1.3-2.9% for molinate, 5.4-10.0% for simetryn, 0.6-1.3% for oxadiazon, 0.2-0.9% for thiobencarb, 1.8-6.6% for isoprothiolane, 0.3-2.1% for diazinon. and 0% for fenitrothion. PMID- 11766810 TI - Simulated formation and flow of microemulsions during surfactant flushing of contaminated soil. AB - Contamination of groundwater resources by non-aqueous phase liquids (NAPLs) has become an issue of increasing environmental concern. This study investigated the formation and flow of microemulsions during surfactant flushing of NAPL contaminated soil using the finite difference model UTCHEM, which was verified with our laboratory experimental data. Simulation results showed that surfactant flushing of NAPLs (i.e., trichloroethylene and tetrachloroethylene) from the contaminated soils was an emulsion-driven process. Formation of NAPL-in-water microemulsions facilitated the removal of NAPLs from contaminated soils. Changes in soil saturation pressure were used to monitor the mobilization and entrapment of NAPLs during surface flushing process. In general, more NAPLs were clogged in soil pores when the soil saturation pressure increased. Effects of aquifer salinity on the formation and flow of NAPL-in-water microemulsions were significant. This study suggests that the formation and flow of NAPL-in-water microemulsions through aquifer systems are complex physical-chemical phenomena that are critical to effective surfactant flushing of contaminated soils. PMID- 11766811 TI - Development of chlorine dioxide-related by-product models for drinking water treatment. AB - Factorial experiments were conducted using source waters from seven drinking water treatment plants in Ontario, Canada to develop statistically based model equations capable of predicting chlorine dioxide consumption and chlorite and chlorate formation upon chlorine dioxide application. The equations address raw water quality and operational parameters including pH, temperature, chlorine dioxide concentration, reaction time and water organic content (as described by non-purgeable organic carbon x ultraviolet absorbance measured at 254 nm, NPOC x UV254). Terms describing two-factor interaction effects were also included, improving the accuracy of the predictive equations in fitting measured response concentrations as evaluated through internal and external validations. Nearly 80% of the predictions for chlorine dioxide consumption and chlorite formation were observed to be within 20% of the measured levels. Over 90% of the predicted chlorate levels were within +/- 0.1 mg/L of the measured levels. Chlorine dioxide concentration and NPOC x UV254 were key parameters when developing the predictive models. PMID- 11766812 TI - Long-term (1956-1999) dynamics of phosphorus in a shallow, subtropical Chinese lake with the possible effects of cyanobacterial blooms. AB - This paper describes the long-term dynamics of phosphorus concentrations in both the lake water and the sediment in a subtropical Chinese lake, Lake Donghu. The total phosphorus (TP) concentration in the lake water experienced an upward trend from the 1950s, and peaked in 1983/1984, but declined obviously afterwards. From the 1950s to thel990s. TP content in the upper 10cm sediment of the lake increased steadily from 0.307 to 1.68mg P gDW(-1) at Station I and from 0.151 to 0.89 mg P g DW(-1) at Station II, respectively. The TP increase in the lake water before mid-1980s was mainly attributed to the massive input of sewage P. The outbreak of cyanobacterial blooms coincided with the peaks of TP and Orthophosphate (PO4-P) in the water in mid-1980s, and the maximum TP of the water reached as high as 1.349mg/l at Station I and 0.757mg/l at Station II (in 1984), respectively. The declines of TP and P04-P in the water after mid-1980s was coincident with the disappearance of cyanobacterial bloom. PMID- 11766813 TI - Mathematical relationships between vapor pressure, water solubility, Henry's law constant, n-octanol/water partition coefficent and gas chromatographic retention index of polychlorinated-dibenzo-dioxins. AB - Mathematical relationships between vapor pressures (P), water solubilities (S), Henry's law constants (Hc). noctanol/water partition coefficients (Kow) and gas chromatograph retention indices (GC-RIs) of polychlorinated-dibenzo-dioxins (PCDDs) were established. A model equation was established between GC-RIs (= RI) and other physico-chemical parameters (K) of PCDDs in the form of log K = aRI2 + bRI + c with correlation coefficients (R2) greater than 0.97, except Hc. These equations were derived from 56 experimental data of PCDDs reported previously. The values of P, S, Hc and Kow of PCDDs predicted by these equations based on their GC-RIs in the present study deviated from those calculated by the SOFA method in a previous study by only 0.19, 0.13, 0.18 and 0.096 log units, respectively. PMID- 11766814 TI - Neural network modeling of salinity variation in Apalachicola River. AB - Salinity is an important indicator for water quality and aquatic ecosystem in tidal rivers. The increase of salinity intrusion in a river may have an adverse effect on the aquatic environment system. This study presents an application of the artificial neural network (ANN) to assess salinity variation responding to the multiple forcing functions of freshwater input, tide, and wind in Apalachicola River, Florida. Parameters in the neural network model were trained until the model predictions of salinity matched well with the observations. Then, the trained model was validated by applying the model to another independent data set. The results indicate that the ANN model is capable of correlating the non linear time series of salinity to the multiple forcing signals of wind, tides. and freshwater input in the Apalachicola River. This study suggests that the ANN model is an easy-to-use modeling tool for engineers and water resource managers to obtain a quick preliminary assessment of salinity variation in response to the engineering modifications to the river system. PMID- 11766815 TI - Improving anaerobic sequencing batch reactor performance by modifying operational parameters. AB - A lab-scale anaerobic sequencing batch reactor (ASBR) that had operated with glucose at an organic loading rate of 2.1 kg COD m(-3) d(-1) was stressed with an organic loading rate of 3.2 kg COD m(-3) (-1). Five different combinations of influent concentration, total cycle time, and fill time to cycle time ratio were examined. No external pH control was used. In all cases, acetate and propionate were the main constituents of the effluent. Larger fill time to cycle time ratios and lower initial substrate concentrations resulted in improved performance suggesting that ASBR operation may be improved by changing operational parameters. PMID- 11766816 TI - Association of coliform bacteria with wastewater particles: impact of operational parameters of the activated sludge process. AB - The fraction of particles with associated coliform bacteria (PAC) in the activated sludge process was evaluated using a 16S rRNA oligonucleotide probe specific to the family Enterobacteriaceae. The PAC was found to decline exponentially with increasing mean cell residence times (MCRTs). The factors influencing the formation of PAC, identified with simplified mass balance relationships. are the concentration of particles, the concentration of dispersed (non-particle associated) coliform bacteria, and the MCRT. The concentration of dispersed coliform bacteria was found to decline with increasing MCRTs. The rate of decline was greater than the typical half-life attributed to endogenous decay, suggesting that other factors (e.g., predation by protozoa) influence the concentration of dispersed coliform bacteria, and subsequently the formation of PAC. Given that the association of targeted organisms with particles adversely impacts the performance of a disinfection system, studies targeted at the fate of organisms other than coliform bacteria in the activated sludge process are of paramount importance in assessing the health risks of post-disinfected effluents. PMID- 11766817 TI - Biochemical model of glucose induced enhanced biological phosphorus removal under anaerobic condition. AB - Enhanced biological phosphorus removal (EBPR) is playing an increasingly important role in controlling the eutrophication phenomenon in natural waters. It is believed that substrates other than acetate exert significant effects on the EBPR process. In this research, it was found that glucose could be used as the dominant substrate to induce and maintain a successful EBPR process. However, compared to the conventional EBPR process using acetate as the dominant substrate, it was found that less PO4-P was released into the medium and 3 hydroxyvalerate (3-HV) enriched poly-beta-hydroxyalkanoate (PHA), rather than 3 hydroxybutyrate (3-HB) enriched PHA, was accumulated during the anaerobic condition. According to the experimental results, a new biochemical model is hypothesized for the anaerobic metabolism of glucose. It is reasoned that the predominance of 3-HV enriched PHA is employed to balance the internal redox during the anaerobic condition. The Entner-Doudoroff (ED) pathway is likely used for anaerobic glucose metabolism when the bacteria demonstrate good EBPR performance, because the ED pathway necessitates the use of polyphosphate for energy purposes. PMID- 11766818 TI - Photocatalytic degradation of nitrotoluene in aqueous TiO2 suspension. AB - TiO2-mediated photocatalytic degradation process was employed to treat aqueous 2 , 3- and 4-NT (nitrotoluene) pollutants. The NT disappearance and TOC removal rates for three isomers showed no significant differences. Three hydroxylated aromatic intermediates resulting from the photocatalytic degradation of 4-NT were identified; this suggested two (initial) degradation pathways. Formation of acetic acid, formic acid, and formaldehyde was also noted. The mineralization products included NH4+, NO3- and CO2. N2 bubbling or the presence of a positive hole acceptor during 4-NT degradation resulted in a high 4-aminotoluene formation. This indicated an effective reduction of 4-NT's nitro group to amino moiety. Generally, Pt-loaded TiO2 (Pt-TiO2) had no influence on the disappearance rate of 4-NT. However, the use of Pt-TiO2 along with a higher light intensity source resulted in an accelerated TOC removal. PMID- 11766819 TI - Chlorination of natural organic matter: kinetics of chlorination and of THM formation. AB - The kinetics of the formation of trihalomethanes (THMs) and of chlorine consumption for the chlorination of natural organic matter with an excess of chlorine (50 microM > [Cl2]o >210 microM) was investigated. THM precursors could be divided into a fast and a slowly reacting fraction. Long term chlorine demand and the formation of THM could be described by second order kinetics. Rate constants were between 0.01 and 0.03 M(-1) s(-1) in the pH range 7-9 for surface waters and humic materials extracted from surface waters. A groundwater gave a higher rate constant of 0.124 M(-1) s(-1). Resorcinol-type structures were tested with respect to kinetics and yield of THM formation. They could possibly be responsible for the fast reacting THM precursors. which represent 15-30% of the THM precursors of natural waters. Additional classes of compounds that might contribute to the initial THM formation include readily enolizable compounds such as beta-diketones and beta-ketoacids. Experiments with phenol showed that slowly reacting THM precursors may consist of phenolic compounds. The influence of pretreatments (UV/visible irradiation, ozone and chlorine dioxide) on chlorine demand and THM formation from NOM was also studied: UV/visible irradiation does not alter THM formation but leads to a higher chlorine demand. Preoxidation with ozone leads to a lower THM formation with an unaltered chlorine demand and preoxidation with chlorine dioxide reduces THM formation and the chlorine demand. PMID- 11766820 TI - Electrochemical generation of hydrogen peroxide from dissolved oxygen in acidic solutions. AB - Hydrogen peroxide (H2O2) was electro-generated in a parallel-plate electrolyzer by reduction of dissolved oxygen (DO) in acidic solutions containing dilute supporting electrolyte. Operational parameters such as cathodic potential, oxygen purity and mass flow rate, cathode surface area. pH, temperature, and inert supporting electrolyte concentration were systematically investigated as to improve the Faradic current efficiency of H2O2 generation. Results indicate that significant self-decomposition of H2O2 only occurs at high pH (> 9) and elevated temperatures (> 23 degrees C). Results also indicate that the optimal conditions for H2O2 generation are cathodic potential of -0.5 V vs. saturated calomel electrode (SCE), oxygen mass flow rate of 8.2 x 10(-2) mol/min, and pH 2. Under the optimal conditions, the average current density and average current efficiency are 6.4A/m2 and 81%, respectively. However, when air is applied at the optimal flow rate of oxygen, the average current density markedly decreases to 2.1 A/m2, while the average current efficiency slightly increases to 90%. The limiting current density is 6.4 A/m2, which is independent of cathode geometry and surface area. H2O2 generation is favored at low temperatures. In the concentration range studied (0.01-0.25 M), the inert supporting electrolyte (NaClO4) affects the total potential drop of the electrolyzer, but does not affect the net generation rate of H2O2. PMID- 11766821 TI - A method for the rapid detection of microbial contaminants in animal cell culture processes. AB - The early detection of microbial contamination is an important issue in the production of biopharmaceuticals using animal cell culture systems. A new method, based on the ChemScan RDI analyser, was evaluated for the rapid detection and enumeration of low concentrations of microorganisms within a large population of animal cells and in cell culture media. The method was tested with suspension cell cultures and is applicable to adherent cell cultures. In both cases, the method uses an initial step to eliminate the animal cells followed by collection and fluorescent labelling of the viable microbial contaminants on a filter membrane. Total counts of the viable microorganisms were obtained after analysis of the membrane by the ChemScan RDI analyser. The results showed that the ChemScan RDI detected individual bacterial cells after filtration of the pre treated animal cell culture. The detection limit of the ChemScan RDI was less than 10 bacteria/ml in cell culture containing 10(6) mammalian cells/ml and one bacterium in 500 ml of cell culture medium. A strong correlation between the standard plate count and the ChemScan RDI was observed, even at low bacterial concentrations. The total time for each analysis was less than two hours. PMID- 11766822 TI - Method for qualifying microbial removal performance of 0.1 micron rated filters. Part I: characterization of water isolates for potential use as standard challenge organisms to qualify 0.1 micron rated filters. AB - Although 0.1 microm rated filters intended for pharmaceutical sterilization applications have been commercially available for at least 15 years, there is no industry-wide standard for qualifying the microbial removal performance of these filters. In this article, we report on the bacterial challenge methodology used to screen four bacterial species for potential utility as a standard challenge organism to qualify 0.1 microm rated filters. These isolates were, in their natural state, demonstrated to penetrate 0.2/0.22 microm rated filters in prior studies. In the screening challenges described in this study, three out of these four candidates tested demonstrated consistent penetration of one 0.22 microm rated filter type tested (when cultured in a low nutrient medium under standard laboratory conditions). These included 6204-22 (FAME ID Acidovorax avenae citrulli), 6266-15 (FAME ID Comamonas acidovorans), and 6266-34 (FAME ID Hydrogenophaga pseudoflava). Of these, H. pseudoflava (6266-34) was chosen for additional experiments with other 0.2 microm rated filter membranes. In total, seventeen 0.2 and 0.22 microm rated filter discs, spanning five different "sterilizing grade" filter types from three different filter manufacturers were tested. H. pseudoflava penetration was observed for every filter tested. Under the same challenge conditions, H. pseudoflava was consistently retained by a 0.1 microm rated hydrophilic PVDF (polyvinylidenefluoride) filter with a specified high titer reduction claim for Acholeplasma laidlawii. In order to ensure selection of the most stable penetrative phenotype (i.e., select for nonrevertants), H. pseudoflava was subjected to three rounds of "filter cloning," and these results are described herein. The advantages of using H. pseudoflava for qualifying the microbial removal performance of 0.1 microm rated filters are also discussed. PMID- 11766823 TI - Method for qualifying microbial removal performance of 0.1 micron rated filters. Part II: preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for use as a standard challenge organism to qualify 0.1 micron rated filters. AB - In this article, we report on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. Filter-cloned H. pseudoflava (ATCC 700892) was easily cultured in a low nutrient broth (R2A broth) under standard laboratory conditions, reaching high titers of 10(8)-10(9) cfu/mL within 48-65 hours of incubation at 25+/-5 degrees C. Under these conditions, H. pseudoflava is a rod-shaped bacterium, averaging 0.25+/-0.03 microm by 1.65+/-0.35 microm, and appears to be smaller than Brevundimonas diminuta in width (0.31+/-0.03 microm), but somewhat longer in length (0.88+/-0.19 microm), which may partly explain the observed penetration. In total, thirty-five 0.2/0.22 microm rated filter discs, spanning five different "sterilizing grade" filter types from two different filter manufacturers were challenged with H. pseudoflava. In all cases, H. pseudoflava was shown to consistently penetrate every 0.2/0.22 microm rated filter disc tested. These tests also spanned three different challenge durations, including short-term challenges (30-40 minutes), and two different challenge fluids. The use of serial (double) 0.22 mm rated filters, which is a common industry practice to reduce the prefiltration bioburden to the final "sterilizing" filter, was also shown to be inadequate to fully retain H. pseudoflava under the challenge condition used. In contrast, two different 0.1 microm rated filter types functionally qualified with a specified high titer reduction claim for Acholeplasma laidlawii, were shown to consistently and fully retain H. pseudoflava, and retention by these two filter types was shown to be robust and independent of the challenge duration. PMID- 11766824 TI - Method for qualifying microbial removal performance of 0.1 micron rated filters. Part III: bacterial challenge tests on 0.2/0.22 and 0.1 micron rated filter cartridges with Hydrogenophaga (formerly Pseudomonas) pseudoflava. AB - We have previously reported on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. This article reports on the retention efficiencies of a large panel of 0.2/0.22 microm and 0.1 microm rated filter cartridges for H. pseudoflava (ATCC 700892) versus the retention capabilities of the same filters for Brevundimonas diminuta (ATCC 19146). A total of thirty-two 0.2/0.22 microm rated filter cartridges, spanning nine different "sterilizing grade" filter types from four different filter manufacturers, were challenged with H. pseudoflava at challenge levels exceeding 10(7) cfu/cm2. H. pseudoflava was shown to penetrate every 0.2/0.22 microm rated filter tested, with log titer reduction (LTR) values ranging from 3.5 to 7.7 logs. H. pseudoflava was shown to be more penetrative than B. diminuta under the same challenge conditions. B. diminuta was fully retained by nineteen of the twenty 0.2/0.22 microm rated filters that were challenged with both organisms. In the case of 0.1 microm rated filters, eighteen filter cartridges, spanning five different filter types from three manufacturers were tested. H. pseudoflava was consistently retained by four out of the five filter types tested, with LTR values in excess of 11.5 to 12.2 logs. The 0.1 microm rated filter type that was penetrated by H. pseudoflava has been previously demonstrated to be not fully retentive for naturally occurring bacteria. The data show that H. pseudoflava penetrates 0.2/0.22 microm rated filters just as readily as B. diminuta penetrates 0.45 microm rated filters. In addition, titer reductions provided by 0.2/0.22 microm rated filters for H. pseudoflava are comparable to those reported for A. laidlawii mycoplasma, albeit under different conditions. This study demonstrates that H. pseudoflava meets all criteria for use as a standard organism for qualifying the microbial removal performance of 0.1 microm rated filters for enhanced sterility assurance. PMID- 11766825 TI - Sorption of parabens by fluoropolymer or fluoropolymer laminated flexible tubing. AB - Earlier studies using methylparaben and propylparaben showed extensive losses due to sorption by silicone, polyvinyl chloride, and other flexible tubing. As much as 100% loss of propylparaben and significant loss of methylparaben was reported within 24 hours using Tygon, Clearflo, or Silastic tubing. The fluoropolymer Teflon FEP did not show sorption losses. The current study was conducted using three different fluoropolymer resin tubing pieces (FEP, PFA, and NXT or PTFE) as well as a Tygon tubing lined with FEP to show that these do not show paraben sorption losses over an extended period of time. The results of this study show that sorption losses can be avoided or reduced by proper selection of flexible tubing. PMID- 11766826 TI - Filter validation: bacterial hydrophobicity, adsorptive sequestration and cell size alteration. PMID- 11766827 TI - Spontaneous ventricular arrhythmias following partial left ventriculectomy for nonischemic dilated cardiomyopathy: relation to hemodynamics and survival. AB - The study assessed the value of ambulatory electrocardiogram (AECG) monitoring for identification of patients who are at increased risk for cardiac death or arrhythmic event following partial left ventriculectomy (PLV). Furthermore, the impact of PLV and its hemodynamics on the occurrence of spontaneous ventricular arrhythmias was assessed in long-term survivors. In 32 idiopathic dilated cardiomyopathy patients who underwent PLV, ambulatory ECG (AECG) was performed preoperatively, early postoperatively, and 6 months and 12 months after surgery. In 17 of 19 patients who survived > 12 months after the procedure, left ventricular (LV) angiography was performed at the same time points and was used to calculate LV ejection fraction, and end-diastolic and end-systolic wall stress. During a mean follow-up of 478 +/- 405 days, 11 cardiac events occurred. Cox univariate regression revealed frequency of premature ventricular contractions > 30/hour at baseline (p = 0.0213) and duration of heart failure symptoms (p = 0.0226) as predictors of cardiac death or arrhythmic event after PLV. In a multivariate analysis, only frequency of premature ventricular contractions > 30/hour was a significant predictor. There was no change in the frequency or severity of ventricular arrhythmias after PLV. However, frequency of premature ventricular contractions correlated with LV end-diastolic stress (r = 0.35, p = 0.013), and ejection fraction (r = -0.34, p = 0.016). Preoperative AECG monitoring may help stratification of PLV patients. Serial AECG did not show that PLV influence the incidence or the complexity of spontaneous ventricular arrhythmias. In contrast, it appears that a hemodynamically "successful" procedure may decrease the incidence of ventricular arrhythmias. PMID- 11766828 TI - Safety and feasibility of a cardiac support device. AB - The Cardiac Support Device (CSD), a preformed-knitted polyester device surgically placed over the cardiac ventricles, prevents left ventricular (LV) remodeling and improves LV ejection fraction (EF) in dogs with heart failure (HF). This study was designed to examine the safety of the CSD in patients with advanced HF. As of December 31, 1999, the CSD was implanted into 22 patients with myocardial disease. Ten patients had concomitant mitral valve repair, two patients had valve replacement (one patient aortic and one patient mitral), one patient had LV assist device (LVAD) placement, and eight patients received only the CSD. The CSD was placed while on bypass with the heart beating, attached to the epicardium groove, and tailored anteriorly to snugly fit the ventricles. There were no intraoperative deaths or complications. Two patients died early from non-CSD related causes 4 and 23 days postoperatively; one late death occurred. Of the remaining 19 patients, none had any CSD-related adverse events during an average 3.5 +/- 0.4 month follow-up. All patients had completed 3-month follow-up. No patients had evidence of constrictive and/or restrictive physiology. Mitral valve regurgitation (MVR) improved in all patients. [table: see text] Initial findings indicate that the CSD is safe and improves heart failure symptoms and LV function. Additional studies and longer follow-up are needed to confirm these results. PMID- 11766829 TI - Acute ventricular reduction with the acorn cardiac support device: effect on progressive left ventricular dysfunction and dilation in dogs with chronic heart failure. AB - BACKGROUND AND AIM: Surgical resection of myocardium that acutely reduces left ventricular (LV) volume in patients with advanced heart failure (HF), the so called "Batista Operation," remains controversial. We examined the effects of acute LV reduction with the Acorn Cardiac Support Device (CSD) in dogs with HF (LV ejection fraction < 30%). METHODS: HF was produced in 15 dogs by intracoronary microembolization. In nine dogs, intravenous dobutamine was administered to reduce LV end-diastolic dimension (LVEDD) by 10%-25%. While on dobutamine infusion, the CSD, a preformed knitted polyester device, was surgically placed around the ventricles, anchored to the arteriovenous (AV) groove, and tailored anteriorly to fit snugly over the ventricles. Dogs were then weaned off dobutamine. RESULTS: On average, the procedure reduced LVEDD by 7 +/- 1 mm (range 5-12 mm). Of the nine dogs, two died before completion of the study and seven survived for the entire period. Six dogs did not undergo device placement and served as controls. All were followed for 3 months prior to sacrifice. In controls, LV end-diastolic volume increased after 3 months (66 +/- 5 mL vs 77 +/- 6 mL; p = 0.007), while in CSD-treated dogs (n = 7), it decreased (80 +/- 5 mL vs 60 +/- 3 mL; p = 0.002). In controls, LV ejection fraction (EF) decreased after 3 months (27 +/- 1% vs 23 +/- 1%; p = 0.001) but was unchanged in CSD-treated dogs (25 +/- 1% vs 26 +/- 1%; p = 0.66). Compared to controls, CSD treated dogs showed improved LV diastolic dysfunction and chamber sphericity, decreased wall stress, and no functional mitral regurgitation (MR). CONCLUSION: In dogs with advanced HF, acute LV reduction with the Acorn CSD prevents progressive global LV dilatation and ameliorates functional MR. PMID- 11766830 TI - Growth hormone treatment in dilated cardiomyopathy. AB - Treatment with human recombinant growth hormone (GH) has yielded conflicting results in patients with congestive heart failure. We analyzed the baseline somatotrophic axis in 50 patients with dilated cardiomyopathy. Then, a double blind, randomized, placebo-controlled study of GH was performed. We randomly allocated these patients to treatment with subcutaneous GH (2 IU daily) or placebo for a minimum of 12 weeks. The primary end-points were the effect on left ventricular (LV) mass and systolic wall stress. The secondary endpoint was LV ejection fraction. Severity of heart failure as determined by cardiac index, LV end-diastolic diameter, and plasma noradrenaline concentrations correlated markedly with baseline serum insulin-like growth factor-1 (IGF-1) levels. Patients in the GH group had an increase in LV mass compared with the placebo group (p = 0.0001). There was no significant difference in LV systolic wall stress, mean blood pressure, or systemic vascular resistance between the two groups. New York Heart Association (NYHA) functional classification and distance in 6-minute walk test remained unchanged. The change in IGF-1 concentrations between GH and placebo group was notably related (p = 0.0001) to the change in LV mass (p = 0.0001). The GH-induced increase of IGF-1 predicted the changes of ejection fraction (p < 0.05). A marked increase of ejection fraction of 7% was observed in patients whose IGF-1 increased by more than the median increase, in comparison to the patients with an increase below the median (p = 0.03). Serum levels of IGF-1 reflecting GH secretion are diminished in relation to severity of heart failure in patients with dilated cardiomyopathy. GH-induced increases of IGF-1 of more than 80 pg/mL caused notable improvement of ejection fraction. There is a marked increase in LV mass in patients with dilated cardiomyopathy given GH. Changes in LV mass are related to changes in serum IGF-1 concentrations. PMID- 11766831 TI - Myocardial revascularization of the beating heart in high-risk patients. AB - OBJECTIVE: Myocardial revascularization without cardiopulmonary bypass (CPB) has been proposed as an alternative technique in patients at high risk for conventional coronary artery bypass grafting (CABG). The purpose of this article is to evaluate the potential benefit of such an approach. METHODS: We retrospectively evaluated the perioperative results of off-pump CABG (OPCAB) performed from January 1995 to December 1999. Patients were divided into three groups on the basis of their preoperative risk factors: age greater than 80 years, reoperative CABG, and left ventricular ejection fraction percentage (LVEF%) less than 40%. The three subgroups were compared with patients operated on-CPB (ONCAB) during the same period of time. A total of 172 octogenarians had ONCAB versus 97 OPCAB, 307 reoperations were ONCAB versus 274 OPCAB, and 514 patients with LVEF% less than 40% were operated ONCAB versus 220 OPCAB. RESULTS: Preoperative comorbidities were homogeneously distributed in the OPCAB and ONCAB groups. More extensive coronary artery disease was found in the ONCAB groups. A trend for a lower number of perioperative complications was reported in the OPCAB groups. Freedom from overall complications was significantly higher (p < 0.005) in the OPCAB group. Actual mortality rates in the OPCAB and ONCAB groups were comparable (p = NS). CONCLUSIONS: CABG can be performed safely without CPB in patients with a high preoperative risk profile. Freedom from perioperative complications is markedly higher when the OPCAB approach is utilized. PMID- 11766832 TI - Transventricular mitral annuloplasty in a patient undergoing partial left ventriculectomy. AB - A 70-year-old male patient with heart failure resulting from dilated cardiomyopathy underwent a partial left ventriculectomy between the papillary muscles and a newly devised transventricular mitral annuloplasty. Intraoperative transesophageal Doppler echocardiography revealed reduced ventricular dimensions and corrected mitral insufficiency with unchanged ventricular filling patterns, allowing prompt recovery despite unchanged myocardial pathology. PMID- 11766833 TI - Partial left ventriculectomy for patients with ischemic cardiomyopathy. AB - BACKGROUND: Partial left ventriculectomy (PLV) has been performed in patients with dilated cardiomyopathy (DCM), but improved myocardial energetics may make PLV useful also for ischemic cardiomyopathy (ICM) unamenable to conventional treatment. METHODS: Of 262 patients undergoing PLV, 94 patients with ICM as the underlying pathology were analyzed and compared with 168 patients with DCM. RESULTS: ICM patients were older (57.3 years vs 50.9 years, p = 0.0001) and heavier (69.7 kg vs 65.9 kg, p = 0.039) than those with DCM, but ventricular end diastolic and end-systolic dimensions were similar with comparably depressed fractional shortening (16% vs 15%, p = 0.294) and equally severe functional limitation [New York Heart Association (NYHA) Class 3.7 vs 3.6, p = 0.734]. A majority of patients in both groups underwent lateral PLV (76% vs 74%, p = 0.883) with myocardium excised between papillary muscles and simultaneous mitral valvuloplasty (41% vs 74%, p < 0.0001). Because ICM patients required coronary artery bypass grafting (CABG) more frequently (79% vs 0.6%, p < 0.0001), operation was more extensive in terms of bypass time (74 minutes vs 47 minutes, p < 0.0001), percentage requiring cardiac arrest (43% vs 19%, p < 0.0001), and arrest duration (34 minutes vs 28 minutes, p = 0.280), but all had similar resection and postoperative ventricular dimensions. Nonetheless, ICM patients required shorter intensive care unit (ICU) time (4.4 days vs 5.9 days, p = 0.048) and similar postoperative hospital stays, resulting in similar hospital survival rates (69% vs 71%, p = 0.778) and functional capacity in long-term follow-up. CONCLUSIONS: Results suggest that PLV can be performed in patients with ICM with comparable risks and benefits as in DCM. Relative efficacy of CABG and mitral repair as compared to volume reduction remains to be studied. PMID- 11766834 TI - Intermediate-term results after partial left ventriculectomy for end-stage dilated cardiomyopathy: is there a survival benefit? AB - BACKGROUND: The mortality of congestive heart failure remains high despite advances in medical therapy. Partial left ventriculectomy (PLV) has been advocated as a surgical alternative for select patients with dilated cardiomyopathy. METHODS: A prospective clinical trial of PLV for patients with end-stage idiopathic dilated cardiomyopathy was performed. Inclusion criteria were left ventricular end-diastolic diameter (LVEDD) greater than 7 cm, refractory New York Heart Association (NYHA) Class IV symptoms, and severely depressed exercise oxygen consumption. RESULTS: Twenty patients underwent PLV with mean follow-up of 21.1 months. Sixteen were male; mean age was 50.1 years +/ 12.0 years (range 25-67 years). Left ventricle (LV) ejection fraction improved after surgery from 14.1% +/- 4.7% to 24.1% +/- 3.1% (p < 0.05, t-test) and this improvement persisted up to 3 years after operation. LVEDD and NYHA Class also were notably improved. There were two early deaths for an operative mortality of 10% (2 of 20 patients). Nine patients after initial improvement in clinical status and LV function developed worsening congestive heart failure (CHF). Six of the 9 ultimately died of complications secondary to CHF. One-, 2-, and 3-year survival rates were 84%, 64%, and 40%, respectively, by Kaplan-Meier analysis. The other three patients required listing for transplantation because of recurrent NYHA Class IV symptoms. Freedom from death or the need for listing for transplantation at 1, 2, and 3 years was 65%, 53%, and 33%, respectively. The remaining nine patients all had improvement in their NYHA classification. CONCLUSIONS: PLV can be performed with acceptable early and intermediate term mortality; survival compares favorably to reports of similar groups of patients treated with medical therapy alone. PMID- 11766835 TI - Volume reduction surgery for end-stage heart failure: experience in Korea. AB - Partial left ventriculectomy (PLV) is regarded as one of the alternatives to heart transplantation for idiopathic dilated cardiomyopathy (d-CMP). Between June 1996 and March 2000, 20 patients underwent left ventricular volume reduction surgery at five major cardiac centers in Korea. PLV was performed in 16 patients with d-CMP and in 1 patient with ischemic CMP. The modified Dor procedure was performed in three patients; two patients with d-CMP and one patient with ischemic CMP. Median age was 35 years (range 3-64 years). There were 13 male and 7 female patients; there were 4 patients in Class III and 16 patients in Class IV. Among the 16 patients in Class IV, 5 patients were inotropic dependent, 2 patients were resuscitated from cardiac arrest or shock in hospital, and 1 patient was treated with intra-aortic balloon pumping. Operative technique for PLV was the same as described by Batista and colleagues. For the modified Dor procedures, the apical left ventricle was opened and a circumferential pursestring suture was placed at the base of both papillary muscles to reduce the diameter of the left ventricle concomitant with mitral annuloplasty. Mitral valve repair was performed in 15 patients and mitral valve replacement was performed in 1 patient. Moderate-to-severe tricuspid regurgitation was noted in 12 patients (with tricuspid annuloplasty in 11 of these patients and replacement in 1 patient). Postoperatively, there were seven operative deaths after PLV and one death after the modified Dor procedure. Cause of death after PLV was right heart failure in four of the seven cases, sepsis in one case, and ventricular tachyarrhythmia in the remaining two cases. After the modified Dor procedure, there was one operative death with left ventricular failure. Postoperatively, mean ventricular end-diastolic dimension markedly decreased from 75.3 mm to 50.9 mm. However, this dimension had increased slightly to 58.2 mm, an average observed 22 months later. Mean left ventricular ejection fraction (LVEF) improved significantly from 20.6% to 33.5% (p < 0.0001), but decreased to 28.5% on average 22 months later (p = 0.058). Eleven patients were discharged from the hospital and followed-up for a mean of 20.2 months (range 1-41 months). During the early postoperative period, most were in good condition. However, heart failure progressed with mitral regurgitation in four patients, two of whom underwent heart transplantation. In conclusion, PLV for d-CMP seems to be an effective alternative surgical procedure to heart transplantation in Korea. The modified Dor procedure may be another alternative to transplantation for left ventricular volume reduction. However, in patients showing progression of heart failure, early intervention with ventricular assist or heart transplantation will be necessary. Also, further studies will be necessary for selection criteria and for prevention of ventricular tachyarrhythmia. PMID- 11766836 TI - Partial left ventriculectomy and limited heart transplantation availability. AB - BACKGROUND AND AIM: Partial left ventriculectomy, a novel cardiac volume reduction operation, is applied in countries without a developed heart transplantation program. We sought to determine its impact in our population of patients. METHODS: Partial left ventriculectomy was performed in 38 patients during the last 4 years. Basic inclusion criteria were nonischemic dilated cardiomyopathy and poor response to medical therapy for heart failure. Hemodynamic evaluation was carried out before and after operation. A modified surgical technique of mitral valve repair and ventricle suturing was applied. RESULTS: Thirty-day, 6-month, and 2-year survival rates were 82% +/- 7%, 65% +/- 8%, and 61% +/- 9%, respectively. Duration of heart failure symptoms was the only predictor of survival (p = 0.042). A high proportion of noncardiac causes of death was noted. Functional capacity in surviving patients improved at every successive measurement up to 1 year postoperatively. CONCLUSIONS: The introduction of partial left ventriculectomy in a country with limited heart transplantation availability had a great impact on the management of end-stage heart failure and may represent the only surgical option for some patients. The average cost per patient was substantially lower when compared to heart transplantation. PMID- 11766837 TI - Beating-heart coronary artery bypass grafting for left ventricular failure assisted by the Abiomed BVS 5000. AB - Two cases of postmyocardial infarction cardiogenic shock were treated with left ventricular assist device (LVAD) implantation. With the left ventricular function bypassed, beating-heart coronary artery bypass grafting (CABG) was performed. This technique may be useful in the setting of acute myocardial dysfunction where limited coronary revascularization is required. PMID- 11766838 TI - Cardiac sarcoma originating from the tricuspid valve. AB - Primary cardiac sarcomas are uncommon. We report an unusual presentation of a cardiac sarcoma that originated from the posterior leaflet of the tricuspid valve. This tumor, which provided a working diagnosis of tricuspid valve myxoma before and during surgery, should be considered in the differential diagnosis of right atrial and ventricular masses. PMID- 11766839 TI - Mitral regurgitation after partial left ventriculectomy as the cause of ventricular redilatation. AB - BACKGROUND: It remains unclear whether ventricular redilatation after partial left ventriculectomy (PLV) is due to underlying pathology or to continued volume overload amenable to surgery. METHODS: Among patients undergoing PLV, 32 had Doppler echocardiography preoperatively, immediately after surgery (< 1 week), early after surgery (1-3 months), and late after surgery (8-14 months). Patients were divided into groups with mitral regurgitation (MR; MR+, n = 16) and without postoperative MR (MR-, n = 16) and were compared for ventricular size, performance, and survival. RESULTS: After initial surgical reduction, left ventricular dimension on average gradually increased back to the preoperative level in subgroups of patients with valvular disease and cardiomyopathy and in all patients combined. Most patients showed drastically reduced left ventricular dimension early after PLV. In MR+ patients, dimension increased back to the preoperative level within 3 months after surgery, whereas the MR- group maintained reduced dimension throughout the first year in all patients combined and in a subgroup of patients with cardiomyopathy. Occurrence of significant MR after PLV appeared to be related to severity of fibrosis in excised myocardium but not to severity of preexisting MR, etiology, or performance of mitral valvuloplasty. CONCLUSIONS: Early postoperative MR, residual or new, appeared to play an important role in dictating early hemodynamics and late outcome in patients undergoing PLV. Results suggest an aggressive simultaneous approach to abolish MR. Causative role of myocardial fibrosis remains unclear and needs further study. PMID- 11766840 TI - Perioperative ventricular arrhythmias in patients undergoing partial left ventriculectomy. AB - BACKGROUND: Although incidence of ventricular arrhythmias after partial left ventriculectomy (PLV) has been reported, there are no studies comparing incidence before and after PLV. Although operative scars may give rise to arrhythmias, improved energetic efficiency after PLV may decrease their incidence. METHODS: Pre- and postoperative ventricular arrhythmias were monitored by Holter ECG and analyzed in 17 patients undergoing PLV in Curitiba, Brazil. RESULTS: Although total 24-hour heart beat (THB) increased significantly (p = 0.018), ventricular premature contractions (VPCs) decreased markedly (p = 0.036), excluding one patient dying in low cardiac output (LOS) who had terminal arrhythmias increased multifold. In the remaining 16 patients, VPC pairs were also reduced significantly on the average (p = 0.038). In contrast, ventricular tachycardia (VT; more than three consecutive VPCs) disappeared in five patients, decreased in two patients, and newly occurred in four patients, with five patients showing no change; one of them developed a prolonged VT, successfully reversed by external cardioversion. CONCLUSIONS: Despite notable significant increase in THB immediately after PLV, PVC and PVC pairs were significantly decreased in contrast to VT, which disappeared in some patients and newly occurred in other patients, remaining constant on the average. Sustained VT occurring in a patient with all other arrhythmias suppressed may suggest a unique electrophysiological substrate, may justify prophylactic use of amiodarone or an implantable cardioverter defibrillator, and may underscore the importance of further and extended studies. PMID- 11766841 TI - Heritability of life span in mice and its implication for direct and indirect selection for longevity. AB - We found high narrow-sense heritability of life span based on the regression of offspring on average parental (midparent) life spans. In two mouse populations prepared using the 4-way-cross design, mean +/- SE heritabilities were 62 +/- 11% (P < 0.001) and 44 +/- 15% (P < 0.01). To reflect inherited rates of aging, rather than resistance to early disease, data from the first 25% to die were deleted, so that only about 40% of families were used for offspring-midparent regressions. Heritabilities still remained high, 38% and 55%, for the same two populations, respectively. Populations studied in two other experiments did not show nearly as high heritabilities; in one case probably due to environmental stress, and in the other probably because the strains used did not have sufficient additive variance in genes regulating longevity. Significant heritabilities occurred only when a wild derived inbred strain was included in the 4-way cross. The age when a female ceased to reproduce appeared to be related to the life spans of her offspring, but only weakly, not approaching significance for any individual experiment. The age when a female became infertile was related to her life span, but the relationship disappeared when short-lived mice were excluded from the analysis. Our findings indicate that, in sufficiently diverse mouse populations, selection for increased longevity should be possible and that the direct selection for parental life span will be a more efficient strategy than selection for female reproductive life span. PMID- 11766842 TI - Amplification of sequence tagged sites in five avian species using heterologous oligonucleotides. AB - Short of a complete genomic DNA sequence, sequence tagged sites (STSs) have emerged as major genomic reagents for the genetic analysis of little-studied ecologically and agriculturally important organisms. Here, we report STS developed for the turkey (Meleagris gallopavo), guinea fowl (Numidea meleagris), Japanese quail (Coturnix coturnix) and pigeon using primers specific for reference DNA sequences of two chicken (Gallus gallus) genes, aggrecan (agc1) and type X collagen (col10). Additional STSs were also developed for turkey, quail and chicken using primers specific for the human apobec-1 gene. The total length of the STSs developed was 5990, 2522, 4127, 1539 and 6600 bp for the turkey, guinea fowl, Japanese quail, pigeon and chicken, respectively. Based on splice site consensus GT and AG sequences, four of the seven agc1-based chicken STS appear to contain introns. The human gene-based STSs showed no significant sequence identity with the reference GenBank sequences. Maximum likelihood, maximum parsimony and neighbour-joining analysis of an agc1-based STS that was common to all five species showed phylogenetic relationships consistent with those previously defined using mitochondria DNA sequences and nuclear gene restriction maps. Additionally, several putative single nucleotide polymorphisms (SNPs) were detected within the STSs, including eight in the turkey, two in the quail, and two in the chicken when multiple sequences were evaluated from each species. This report describes new STSs that are resources for genetic and physical mapping and genome analysis within and among avian species. These resources should further aid in our understanding of the biology of agriculturally important but little-studied guinea fowl and turkey. PMID- 11766843 TI - Comparative DNA sequence analysis of genetic variation in the African grey parrot, Psittacus erythacus. AB - Comparative genome analysis promises to provide an insight into avian species that have been very little studied. To test the feasibility of this approach, we investigated the use of heterologous primers to generate single nucleotide polymorphisms (SNP) in the African grey parrot, Psittacus erythacus, using primers specific for chicken and turkey DNA fragments. Three of the primers were specific for three expressed sequence tagged sites in the turkey and the fourth for a chicken proteoglycan core protein-like DNA sequence. A total of about 2200 bp of the parrot genome was evaluated for DNA sequence variation. Seven SNPs were identified and confirmed by Mendelian segregation. The frequency distribution of the most common nucleotide at each SNP locus in an unrelated group of parrots ranged from 0.84 to 0.97. The percent similarity of each parrot sequence to the reference sequence was inconsistent and ranged from zero to 100%. The primers as well as the nucleotide variants described represent valuable resources for genetic analysis in the parrot. PMID- 11766844 TI - An episode of accelerated amino acid change in Drosophila esterase-6 associated with a change in physiological function. AB - In most lineages of the subgenus Sophophora esterase-6 is a homodimeric haemolymph protein. In the melanogaster subgroup of species it has become a monomer which is mainly expressed in the male sperm ejaculatory duct. Our analyses of esterase-6 sequences from three melanogaster subgroup species and two close relatives reveal a brief period of accelerated amino acid sequence change during the transition between the ancestral and derived states. In this period of 2-6Myr the ratio of replacement to silent site substitutions (0.51) is about three times higher than the values in other lineages of the phylogeny. There are about 50 more replacements in this period than would be predicted from the ratios of replacement to silent site substitutions found elsewhere in the phylogeny. Modelling on the known structure of a related acetylcholinesterase suggests that an unusually high proportion of the replacements in the transitional branch are non-conservative changes on the protein surface. Up to half the accelerated replacement rate can be accounted for by clusters of changes to the face of the molecule containing the opening of the active site gorge. This includes changes in and around regions homologous to peripheral substrate binding sites in acetylcholinesterase. There are also three changes in glycosylation status. One region predicted to lie on the protein surface which becomes markedly more hydrophilic is proposed to be the ancestral dimerisation site that is lost in the transitional branch. PMID- 11766845 TI - Comparative studies of the endonucleases from two related Xenopus laevis retrotransposons, Tx1L and Tx2L: target site specificity and evolutionary implications. AB - In the genome of the South African frog, Xenopus laevis, there are two complex families of transposable elements, Tx1 and Tx2, that have identical overall structures, but distinct sequences. In each family there are approximately 1500 copies of an apparent DNA-based element (Tx1D and Tx2D). Roughly 10% of these elements in each family are interrupted by a non-LTR retrotransposon (Tx1L and Tx2L). Each retrotransposon is flanked by a 23-bp target duplication of a specific D element sequence. In earlier work, we showed that the endonuclease domain (Tx1L EN) located in the second open reading frame (ORF2) of Tx1L encodes a protein that makes a single-strand cut precisely at the expected site within its target sequence, supporting the idea that Tx1L is a site-specific retrotransposon. In this study, we express the endonuclease domain of Tx2L (Tx2L EN) and compare the target preferences of the two enzymes. Each endonuclease shows some preference for its cognate target, on the order of 5-fold over the non cognate target. The observed discrimination is not sufficient, however, to explain the observation that no cross-occupancy is observed - that is, L elements of one family have never been found within D elements of the other family. Possible sources of additional specificity are discussed. We also compare two hypotheses regarding the genome duplication event that led to the contemporary pseudotetraploid character of Xenopus laevis in light of the Tx1L and Tx2L data. PMID- 11766846 TI - Analysis of fragment homology among DNA sequences from cytochrome P450 families 4 and 6. AB - Cytochrome P450s comprise a diverse superfamily of proteins that often share as little as 12% amino acid identity. Accordingly, the identification of novel gene families, subfamilies and alleles has been based primarily on 'benchmark' levels of global amino acid identity and, more recently, phylogenetic relatedness has been used to resolve ambiguous relationships. However, PCR-based cloning strategies have resulted in a large increase in the number of short DNA sequences, particularly among insects. Many of these fragments remain unnamed and even their gene family membership remains unknown due to the uncertainty as to whether these fragments accurately reflect the levels of sequence identity or patterns of evolutionary divergence exhibited by groups of full-length P450 sequences. As a result, the nature of P450 diversity among insects remains obscure. In this paper, P450 sequences belonging to the two major gene families, that is, families CYP4 and CYP6, are analyzed by comparing segments to full length sequences. A parameter called the Segmental Divergence Index is used to characterize segments of P450s with respect to the degree to which they mirror the divergence of full-length sequences. The reliability of these fragments in phylogenetic analyses is also tested. The results of these analyses support the use of some commonly amplified P450 gene fragments for naming new P450 genes and for studies of P450 diversity and evolution. PMID- 11766847 TI - Male-specific DNA markers from African catfish (Clarias gariepinus). AB - We searched for sex-specific DNA sequences in the male and female genomes of African catfish, Clarias gariepinus (Burchell, 1822) by comparative random amplified polymorphic DNA (RAPD) assays performed on pooled DNA samples. Two sex linked RAPD markers were identified from the male DNA pool and confirmed on individual samples, showing good agreement with phenotypic sex. Both markers were isolated, cloned and characterized. The first marker (CgaY1) was nearly 2.6 kb long, while the length of second one (CgaY2) was 458 bp. Southern blot analysis with a CgaY1 probe showed strong hybridizing fragments only in males and not in females under stringent conditions, indicating the presence of multiple copies of CgaY1 in the male genome. When tested by zoo blot on the genomes of two closely related species from the Clariidae family, CgaY1 hybridized to the DNA of Heterobranchus longifilis and generated a faint male-specific band at low stringency. CgaY2 produced similar hybridization pattern in both sexes of C. gariepinus, C. macrocephalus and H. longifilis. Specific primers were designed to the sequences and the markers were amplified in multiplex PCR reactions together with a control band common to all individuals. This allowed for rapid, molecular sexing of the species on the basis of a simple three band (male) versus one band (female) pattern. According to our knowledge these are the first sex-specific DNA markers isolated from a siluroid fish species. PMID- 11766848 TI - New occurrence of microchromosomes B in Moenkhausia sanctaefilomenae (Pisces, Characidae) from the Parana River of Brazil: analysis of the synaptonemal complex. AB - The Moenkhausia sanctaefilomenae specimens showed a karyotype consisting of 2n = 50 chromosomes with 12 metacentrics, 36 submetacentrics and two subtelocentrics. In addition to the basic karyotype, all the males specimens have cells ranging from zero to two B microchromosomes in mitotic metaphases. These chromosomes were not observed in the female specimens. C-band analysis showed a distribution pattern of characteristic heterochromatin with interstitial and centromeric blocks. However, the B chromosomes were faintly stained with C-banding and were not fluorescent with CMA3 staining. The meiotic studies showed the formation of bivalents in metaphase I and in pachytene under an optical microscope. Through synaptonemal complex analysis with an electron microscope, the pachytene showed 25 bivalents completely paired and a small bivalent corresponding to the B chromosomes. In the same preparation, one of the B chromosomes was observed in a univalent form. On the basis of pairing behavior and morphology it is assumed that B chromosomes of M. sanctaefilomenae show homology between them and their evolutionary aspects are discussed. PMID- 11766849 TI - Factors affecting over-the-counter use of aspirin in the secondary prophylaxis of cardiovascular disease. AB - Little is known about the contribution of over-the-counter (OTC) aspirin to cardiovascular prophylaxis. To investigate this, a two-phase cross-sectional study was carried out in nine general practices in North Staffordshire. In the first phase, all patients with cardiovascular disease (CVD) were identified from computer searches using morbidity registers and drug searches. The search also identfied the subgroup receiving prescribed prophylactic aspirin. In the second phase, a questionnaire was posted to all patients with CVD who were not on prescribed aspirin to establish their current use of OTC aspirin. Overall, 69% of the CVD group used aspirin, with 26% of aspirin being OTC. OTC aspirin use was more common in those aged under 65 years, men, and the more affluent. Also, there were significant differences in OTC aspirin use between the various practices. This study shows that a considerable amount of aspirin is used OTC in those with CVD. Its use is influenced by several factors that could be addressed when considering attempts to improve the overall uptake of aspirin. PMID- 11766850 TI - Systematic review of randomised controlled trials of sildenafil (Viagra) in the treatment of male erectile dysfunction. AB - BACKGROUND: Sildenafil (Viagra), a new oral drug for the treatment of erectile dysfunction, was licensed for use across Europe in 1998. AIM: To examine the effectiveness and safety of sildenafil as an oral treatment for erectile dysfunction. DESIGN OF STUDY: Systematic review and meta-analysis. SETTING: All published or unpublished randomised controlled trials comparing sildenafil with a placebo or alternative therapies. METHOD: Published studies were sought by computerised searches of electronic databases using the keywords 'sildenafil' and 'Viagra'. A hand search was also done of the British Medical Journal, Lancet, Journal of the American Medical Association, New England Journal of Medicine, British journal of General Practice, Drug, Inpharma and Scrip. An assessment of quality of all identified studies and data extraction was undertaken independently by two researchers. Results were combined in a meta-analysis where appropriate, using RevMan version 3. RESULTS: Twenty-one trials were identified. All trials showed a statistically significant improvement in erectile or sexual function in patients using sildenafil compared with a placebo. A meta-analysis of 16 trials reporting a global efficacy response showed that men were 3.57 (95% CI = 2.93-4.43) times as likely to have improved erections on sildenafil compared with those on a placebo. The number needed to treat to have one man with improved erections was two. The drug has a relatively safe side-effect profile. CONCLUSIONS: Available research shows that sildenafil is an effective treatment for male erectile dysfunction. Many trial participants had some baseline erectile function and it is probable that in clinical practice, where the erectile function tends to be more impaired, the number needed to treat may be higher. PMID- 11766851 TI - Access to primary care and distance from PCC. Primary Care Center. PMID- 11766852 TI - Vocational training in Europe. PMID- 11766853 TI - Chronic pain. PMID- 11766855 TI - Missed appointments. PMID- 11766854 TI - Chronic pain. PMID- 11766856 TI - TRIPS [letter]. PMID- 11766857 TI - Single-handed practice--the reality. PMID- 11766858 TI - Chronic fatigue syndrome. PMID- 11766859 TI - Equal and opposite reaction to Willis. PMID- 11766860 TI - Poor performance. PMID- 11766861 TI - Barefoot and empty brain? What are we to make of journalistic 'alternative' nonsense? PMID- 11766862 TI - General practice in 1952. PMID- 11766863 TI - General practice, health, and health care--1952, 2002, 2052... PMID- 11766864 TI - As moths to the flame. Primary care, technology, and the next 50 years. PMID- 11766865 TI - The first Balint group. PMID- 11766866 TI - Miguel Torga. Diaries, 1933-1976. PMID- 11766867 TI - The best of times and worst of times. PMID- 11766868 TI - A qualitative study of delay among women reporting symptoms of breast cancer. AB - BACKGROUND: Delayed presentation of symptomatic breast cancer of three months or more is associated with lower survival rates from the disease, yet 20% to 30% of women wait at least three months before consulting their general practitioner (GP) with breast symptoms. AIM: To explore the factors that influence GP consultation by women with breast cancer symptoms. DESIGN OF STUDY: Qualitative analysis of semi-structured interviews. SETTING: Forty-six women with newly diagnosed breast cancer, selected from 185 women recruited to a larger study. METHOD: Interviews were conducted eight weeks after diagnosis of breast cancer, comparing two groups of women divided according to the extent of delay between onset of symptoms and seeking medical care. Fifteen women had sought advice from their GP within two weeks of symptom discovery ('non-delayers' and 31 had waited 12 weeks or more before seeing their doctor ('delayers'). RESULTS: Women with breast symptoms who presented promptly to GPs recognised the seriousness of the symptom they had discovered more quickly than delayers. Perception of seriousness was influenced by the nature of the initial symptom and how far it matched the individual's expectations of breast cancer as a painless breast lump. Other factors affecting help-seeking included attitudes to GP attendance, beliefs about the consequences of cancer treatment, and perceptions of other priorities taking precedence over personal health. CONCLUSIONS: This analysis suggests that women need further information about the different types of breast cancer symptoms to assist symptom recognition, as well as encouragement to seek medical advice if a symptom is ambiguous. In addition, women may benefit from greater awareness of the benefits of early detection and reassurance about the improvements in quality of breast cancer care. PMID- 11766869 TI - Patient costs in anticoagulation management: a comparison of primary and secondary care. AB - BACKGROUND: The demand for anticoagulation management is increasing. This has led to care being provided in non-hospital settings. While clinical studies have similarly demonstrated good clinical care in these settings, it is still unclear as to which alternative is the most efficient. AIM: To determine the costs borne by patients when attending an anticoagulation management clinic in either primary or secondary care and to use this information to consider the cost-effectiveness of anticoagulation management in primary and secondary care, both from the National Health Service and patient perspectives. DESIGN OF STUDY: Observational study comparing two cohorts of patients currently attending anticoagulation management clinics. SETTING: Four primary care clinics in Birmingham and one in Warwickshire, and the haematology clinics at the University of Birmingham Hospitals Trust and the City Hospital NHS Trust. METHOD: The survey of patients attending the clinics was used to ascertain patient costs. This information was then used in conjunction with the findings of a recent randomised controlled trial to establish cost-effectiveness. RESULTS: Patient costs were lower in primary care than in secondary care settings; the mean (standard deviation) costs per visit were Pound Sterling6.78 (Pound Sterling5.04) versus Pound Sterling14.58 (Pound Sterling9.08). While a previous cost-effectiveness analysis from a health sector perspective alone found a higher cost for primary care, the adoption of the societal perspective lead to a marked change in the result: a similar total cost per patient in both sectors. CONCLUSION: There are significantly higher costs borne by patients attending secondary care anticoagulation management clinics than similar patients attending primary care clinics. This study also demonstrates that the perspective adopted in an economic evaluation can influence the final result. PMID- 11766870 TI - Family influences in a cross-sectional survey of higher child attendance. AB - BACKGROUND: A quarter of all consultations are for children, but there is little quantitative evidence documenting what parental factors are important in the decision to consult. AIM: To assess parental factors in higher child attendance (three or more times per year)--the 32% responsible for most (69%) general practice consultations with children. DESIGN OF STUDY: A random sample of 4000 individuals (one per household), including 670 children. SETTING: Six general practices within a 30-mile radius of the administrative centre. METHOD: Parents completed a postal questionnaire for themselves and their child. The adult questionnaire documented lifestyle, attitude to doctors and medicine, Kokko's personality types, perceived health, health anxiety, number of medical problems, medically unexplained somatic symptoms, and willingness to tolerate symptoms. The child questionnaire documented perceived health, the number of medical problems, somatic symptom inventory, willingness to tolerate symptoms, and self-reported attendance. RESULTS: (Adjusted odds ratios, test for trend, 95% confidence intervals.) A response rate of 490/670 (73%) paired adult and child questionnaires was obtained. Reported higher attendance was valid compared with the notes (likelihood ratio positive test = 5.2, negative test = 0.24), and was independently predicted by the child's age, medical problems, council house occupancy, and by the parents' assessment of the severity of the child's ill health. After controlling for these variables, higher attendance was more likely if the parents were higher attenders (adjusted OR = 3.71, 95% CI = 2.31-5.98), and if they perceived their children had medically unexplained physical symptoms (MUPS) (for 0, 1, 2, 3+ symptoms; adjusted ORs (95% CIs) = 1, 3.1 (1.7-5.7), 2.30 (0.97-5.5), 4.2 (1.8-9.6) respectively, P < or = 0.001). Attendance was less likely if they were willing to tolerate symptoms in their children (score for seven normally self-limiting scenarios = 0-17, 18-29 and 30+; adjusted ORs = 1, 0.71, 0.39 respectively, z for trend P = 0.03), willingness to tolerate symptoms and parental perception of child MUPS were associated with council house tenancy and health anxiety. Parents' perception of child MUPS also related to perception of child health and the parents' own MUPS. Parents of higher attenders were more likely to be depressed (HAD depression scale = 0-7, 8-10, 11+ respectively; adjusted ORs (95% CIs) = 1, 2.04 (1.27-3.27), 1.60 (0.75-3.42)) or anxious (anxiety scale 0-7, 8-10, 11+, respectively; adjusted ORs [95% CIs] = 1, 1.60 [0.99-2.58], 1.97 [1.20-3.26]). CONCLUSION: Important parental factors are council house tenancy, the parents' perception of and willingness to tolerate, somatic symptoms in the child, and the parents' own attendance history, health anxiety, and perception of somatic symptoms Doctors should be sensitive to the parental and family factors that underlie the decision to consult and of the needs of parents of high-attending children. PMID- 11766872 TI - Patients' versus general practitioners' assessments of pain intensity in primary care patients with non-cancer pain. AB - Pain is a major cause for visiting a primary care physician. There are, however, few studies on the assessment of pain patients at the primary care level. The aim of this cross-sectional study was to investigate the concordance between general practitioners' (GPs') and patients' assessments of pain intensity and whether this assessment is influenced by the duration or intensity of pain. Seven hundred and thirty-eight patients aged 16 to 75 years, who were visiting a GP because of pain, participated. Both the patients and the GPs rated pain intensity using the horizontal 100 mm Visual Analogue Scale (VAS). Means and correlations were calculated using non-parametric tests. The VAS scales were arbitrarily divided into five grades (one unit = 20 mm) to investigate the concordance between GPs' and patients' assessments of pain intensity. Spearman 's correlation coefficient between GPs' and patients' assessments was 0.31 for non-chronic pain (of duration less than six months) and 0.20 for chronic pain. GPs evaluated graded pain intensity at least one unit lower than patients in 37% of the visits. In one fifth of the visits (20.5%), the GP's rating was at least two units lower than the patient's rating. The more severe the pain as assessed by patients, the greater the non-concordance between patients' and GPs' assessments. There was considerable non-concordance between GPs' and patients' assessments of pain intensity. GPs tended to estimate their patients' pain intensity as clinically significantly lower than the patients themselves, particularly in chronic and severe pain. PMID- 11766871 TI - Psychosocial, lifestyle, and health status variables in predicting high attendance among adults. AB - BACKGROUND: Increasing consultation rates have implications for the organisation of health services, the quality of care, and understanding the decision to consult. Most quantitative studies have concentrated on very high attenders--not those attending five or more times a year, who are responsible for most (60%) consultations--and have assessed neither the role of lifestyle nor patients' attitudes. AIMS: To assess associations with higher than average attendance (five or more times ayear). DESIGN OF STUDY: Postal questionnaire sent to a random sample. SETTING: Four thousand adults (one per household) from six general practices. METHOD: Data were analysed to identify predictors significantly associated with higher than average attendance. RESULTS: The response rate was 74%. Sef-reported attendance agreed with the notes (r = 0.80, likelihood ratio for a positive test = 9.4). Higher attendance was independently predicted by the severity of ill health (COOP score = 0-7, 8-9, and 10+; adjusted odds ratios= 1, 1.72, 1.91 respectively; test for trend P<0.001) and the number of reported medical problems (COOP score = 0, 1, 2, and 3+ respectively; adjusted ORs = 1, 2.05, 2.31, 4.29; P<0.001). After controlling for sociodemographic variables, medical problems, the severity of physical ill health, and other confounders, high attendance was more likely in those with medically unexplained somatic symptoms (0, 1-2, 3-5, and 6+ symptoms respectively, ORs = 1, 1.15, 1.48, and 1.62; P<0.001); health anxiety (Whitely Index = 0, 1-5, 6-7 and 8+ respectively, ORs = 1, 1.22, 1.77, and 2.78; P<0.001); and poor perceived health ('very good', 'good', 'poor' respectively, ORs = 1, 1.61, and 2.93; P<0.001). Attendance was less likely in those with negative attitudes to repeated surgery use (OR = 0.61, 95% CI = 0.47-0.78), or to doctors (Negdoc scale <18, 18-20, and 21+ respectively; ORs = 1, 0.87, 0.67; P<0.001), in those usually trying the pharmacy first (OR = 0.61, 95% CI 0.48-0.78), and those consuming alcohol (0, 1, 2, 3+ units/day respectively; ORs = 1, 0.62, 0.41, 0.29; P<0.001). Anxiety or depression predicted perceived health, unexplained symptoms, and health anxiety. CONCLUSION: Strategies to manage somatic symptoms, health anxiety, dealing with the causes of--or treating--anxiety and depression, and encouraging use of the pharmacy have the potential both to help patients manage symptoms and in the decision to consult. Sensitivity to the psychological factors contributing to the decision to consult should help doctors achieve a better shared understanding with their patients and help inform appropriate treatment strategies. PMID- 11766873 TI - Aetiology of respiratory tract infections: clinical assessment versus serological tests. AB - Two hundred and fifty ambulatory patients with febrile respiratory tract infections were included in a prospective study, aimed at determining the reliability of physicians judgements relating to the aetiology of the infection. Compared with advanced serological testing, physicians' judgements for a bacterial/atypical, rather than viral, aetiology had a negative predictive value of 60% and a positive predictive value of only 50%. We conclude that physicians' ability to assess whether the infectious aetiology of RTI is viral or bacterial/atypical is low and no more reliable than tossing a coin. PMID- 11766874 TI - The nuclear envelope: emerging roles in development and disease. AB - The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, and anchors two major infrastructures--the nuclear lamina and Tpr filaments--to the nuclear perimeter. Proteins of the nuclear envelope mediate a variety of fundamental activities, including DNA replication, gene expression and silencing, chromatin organization, cell division, apoptosis, sperm nuclear remodeling, the behavior of pronuclei, cell fate determination, nuclear migration and cell polarity. Furthermore, mutations in nuclear lamins and lamin-binding proteins cause tissue-specific inherited diseases. This special issue of Cell and Molecular Life Sciences is devoted to recent major advances in the characterization of nuclear envelope proteins and their roles. We offer here an overview of the topics covered in this issue of CMLS, and also discuss the emerging recognition that the nuclear envelope is an organelle critical for a wide range of genetic and developmental activity in multicellular organisms. PMID- 11766875 TI - Inner nuclear membrane proteins: functions and targeting. AB - We summarize the properties of integral membrane proteins that reside in the inner nuclear membrane, including lamin B receptor (LBR), lamina-associated polypeptide (LAP) 1, LAP2, emerin, MAN1 and nurim. Most of these proteins interact with lamins and chromatin. Some data also suggest more speculative functions such as gene regulation and possibly sterol metabolism. Mutations in emerin and nuclear lamins have been associated with muscular dystrophies and lipodystrophy, raising new questions about the functions of inner nuclear membrane proteins. Integral proteins of the inner nuclear membrane are synthesized on the rough endoplasmic reticulum (ER) and reach the inner nuclear membrane by lateral diffusion in the connected ER and nuclear envelope membranes. Associations with nuclear ligands retain them in the inner nuclear membrane. Further investigation of the functions and targeting of inner nuclear membrane proteins are needed to determine how they are involved in human disease. PMID- 11766876 TI - The structure and function of nuclear lamins: implications for disease. AB - The nuclear lamins polymerize to form the nuclear lamina, a fibrous structure found on the inner face of the nuclear membrane. The lamins also appear to form structures within the nucleoplasm. These various lamin structures help to establish and maintain the shape and strength of the interphase nucleus, but recent work also suggests that the lamins have a role in nuclear processes such as DNA replication. Furthermore, mutations in the human lamin A/C gene have recently been linked to several diseases, including Emery-Dreifuss muscular dystrophy. This review discusses the nature of these mutations and the possible effects of lamin mutations on nuclear function. PMID- 11766877 TI - Nuclear transport mechanisms. AB - The term nuclear transport, refers to the movement of a large variety of macromolecules both into and out of the nucleus. Transport must be extremely selective, yet also very efficient. A single type of channel, the nuclear pore complex, mediates all movement across the nuclear envelope. Selectivity is achieved through the use of families of soluble factors that target substrates for import and export and deliver them to their appropriate intracellular destinations. We now have a fairly detailed understanding of the basic mechanisms of protein import into the nucleus. Many of these same principles can be applied to protein export and perhaps RNA export. This review will summarize the current status of what is known about various transport pathways and highlight the questions that remain to be answered. PMID- 11766878 TI - The plant nuclear envelope. AB - This review summarizes our present knowledge about the composition and function of the plant nuclear envelope. Compared with animals or yeast, our molecular knowledge of the nuclear envelope in higher plants is in its infancy. However, there are fundamental differences between plants and animals in the structure and function of the nuclear envelope. This review will compare and contrast these differences for nuclear pore complexes, nuclear transport, inner nuclear envelope proteins and the role of the nuclear envelope during mitosis. In some cases, seemingly 'novel' aspects of plant nuclear envelope function may provide new insight into the animal cell nucleus. PMID- 11766879 TI - Dynamics of the nuclear envelope at mitosis and during apoptosis. AB - The nuclear envelope is a highly dynamic structure that reversibly disassembles and reforms at mitosis. The nuclear envelope also breaks down--irreversibly- during apoptosis, a process essential for development and tissue homeostasis. Analyses of fixed cells, time-lapse, imaging studies of live cells and the development of powerful cell-free extracts derived from gametes or mammalian somatic cells have provided insights on the fate of nuclear envelope proteins during mitosis and apoptosis, and on the mechanisms behind nuclear envelope modifications in these processes. In this review, we discuss evidence leading to our understanding of the dynamics of the nuclear envelope alterations at mitosis and during apoptosis. We also present novel imaging and genetic approaches to the study of nuclear envelope dynamics and function. PMID- 11766881 TI - Lipoxygenase--a versatile biocatalyst for biotransformation of endobiotics and xenobiotics. AB - Lipoxygenase, a member of the arachidonate cascade enzymes, dioxygenates polyenoic fatty acids to finally yield products with profound and distinct biological activity. This review summarizes the available evidence for another role played by lipoxygenases in the metabolism of endobiotics and xenobiotics. Although other mechanisms exist, a direct hydrogen abstraction by the enzyme and the peroxyl radical-dependent chemical oxidation appear to be central to the co oxidase activity of lipoxygenases. Besides polyunsaturated fatty acids, H2O2, fatty acid hydroperoxides, and synthetic organic hydroperoxides support the lipoxygenase-catalyzed xenobiotic oxidation. The major reactions documented thus far include oxidation, epoxidation, hydroxylation, sulfoxidation, desulfuration, dearylation, and N-dealkylation. It is noteworthy that lipoxygenases are also capable of glutathione conjugation of certain xenobiotics. The enzyme system appears to be inducible following exposure to chemicals. Lipoxygenases are inhibited by a large number of chemicals, some of which also serve as co substrates. Available data suggest that lipoxygenases contribute to in vivo metabolism of xenobiotics in mammals. PMID- 11766880 TI - Carboxypeptidases from A to z: implications in embryonic development and Wnt binding. AB - Carboxypeptidases perform many diverse functions in the body. The well-studied pancreatic enzymes (carboxypeptidases A1, A2 and B) are involved in the digestion of food, whereas a related enzyme (mast-cell carboxypeptidase A) functions in the degradation of other proteins. Several members of the metallocarboxypeptidase gene family (carboxypeptidases D, E, M and N) are more selective enzymes and are thought to play a role in the processing of intercellular peptide messengers. Three other members of the metallocarboxypeptidase gene family do not appear to encode active enzymes; these members have been designated CPX-1, CPX-2 and AEBP1/ACLP. In this review, we focus on the recently discovered carboxypeptidase Z (CPZ). This enzyme removes C-terminal Arg residues from synthetic substrates, as do many of the other members of the gene family. However, CPZ differs from the other enzymes in that CPZ is enriched in the extracellular matrix and is broadly distributed during early embryogenesis. In addition to containing a metallocarboxypeptidase domain, CPZ also contains a Cys-rich domain that has homology to Wnt-binding proteins; Wnts are important signaling molecules during development. Although the exact function of CPZ is not yet known, it is likely that this protein plays a role in development by one of several possible mechanisms. PMID- 11766882 TI - Ebola virus: the search for vaccines and treatments. AB - Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection. PMID- 11766883 TI - Neurocan: a brain chondroitin sulfate proteoglycan. AB - Neurocan is a chondroitin sulfate proteoglycan of the lectican family and a component of the extracellular matrix of the central nervous system. It is mainly expressed during modeling and remodeling stages of this tissue. Neurocan can bind to various structural extracellular matrix components, such as hyaluronan, heparin, tenascin-C and tenascin-R, and the growth and mobility factors FGF-2, HB GAM, and amphoterin. Neurocan can also interact with several cell surface molecules, such as N-CAM, L1/Ng-CAM, TAG-1/axonin-1, and an N-cadherin-binding N acetyl-galactosamine-phosphoryl-transferase, and in vitro studies have shown that neurocan is able to modulate the cell-binding and neurite outgrowth promoting activites of these molecules. Current analysis of the molecular structures and substructures involved in homophilic and heterophilic interactions of these molecules and complementary loss-of-function mutations might shed some light on the roles played by neurocan and interacting molecules in the fine tuning of the nervous system. PMID- 11766884 TI - The protein-only theory and the yeast Saccharomyces cerevisiae: the prions and the propagons. AB - The yeast prions represent a very attractive and tractable model for investigating the prion world. The more extensively studied yeast prion [PSI] leads to a propagation model that links auto-aggregation in amyloid formation and inactivation of the cellular function of the yeast 'prion protein' Sup35p. The other prion model, [URE3], appears to be similar in some genetic and biochemical properties. The characterisation of both Sup35p and Ure2p, the two 'prion proteins', mainly focusing on their aggregation properties, support this model. However, some important differences still exist that should be examined carefully. In particular, we have shown that Ure2p aggregation in vivo (monitored by fluorescence of Ure2-GFP fusion) does not necessarily give rise to a [URE3] phenotype. Comparisons of these two systems as well as more recent experiments are discussed in this review. PMID- 11766885 TI - Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections. AB - The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed. PMID- 11766886 TI - Towards new beta-lactam antibiotics. AB - Antibiotics have had a profound impact on human health and belong to one of the largest-selling classes of drugs worldwide. Introduced into industrial production only some half century ago, these miracle drugs have been the main contributors to the recent increase in human life expectancy. However, the accelerated emergence of bacteria that are resistant to multiple antibiotic types now appears as the most serious threat to continuing success in the treatment of infectious diseases. Recent advances in our knowledge of the structures and mechanisms of enzymes in the biosynthetic pathways of penicillins and cephalosporins, amongst the most important antibiotics in current use, have identified a common structural core together with common iron- and cosubstrate-binding motifs. The diversity in the catalytic specificities of these oxygenases using very similar structural platforms suggests that altering the substrate and product specificities of these enzymes should be possible in the laboratory. This opens up new avenues for industrial production and medical utilisation. PMID- 11766887 TI - Negative regulators of cyclin-dependent kinases and their roles in cancers. AB - In the past decade, the discovery and characterization of cyclin-dependent kinases (CDKs), the engine cores of the cell cycle machinery, have advanced our understanding of the cell cycle. Both positive and negative regulators of CDKs have been characterized, accelerating the important research to unravel the mechanisms of the cell cycle disease--cancer. Cancer can originate from overexpression of positive regulators, such as cyclins, or from underexpression of negative regulators, such as CDK inhibitors (CKIs). CKIs are the focus of much cancer research because they are capable of controlling cell cycle proliferation- the Holy Grail for cancer treatment. CDKs can be inactivated by several mechanisms:, (i) by association with CKIs including p16 (INK4a), p15 (INK4b), p21 (Cip1), p27 (Kip1), and p57 (Kip2), (ii) by disassociation from their cyclin regulatory unit, (iii) by dephosphorylation of a conserved threonine residue in the T-loop, and (iv) by adding inhibitory phosphate. Here we discuss what is known about each mechanism with a hope that these insights will become useful in developing strategies to eliminate cancer in the future. PMID- 11766888 TI - Human papillomaviruses and their role in cervical cancer. AB - Human papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably cancer of the cervix, a disease responsible for at least 200,000 deaths per year worldwide. Over 100 different types of HPV have been identified and these can be divided into two groups. Low-risk HPV types are the causative agent of benign warts. High-risk HPV types are associated with cancer. This review focuses on the role of high-risk HPV types in cervical tumorigenesis. Recent work has uncovered new cellular partners for many of the HPV early proteins and thrown light on many of the pathways and processes in which these viral proteins intervene. At the same time, structural and biochemical studies are revealing the molecular details of viral protein function. Several of these new avenues of research have the potential to lead to new approaches to the treatment and prevention of cervical cancer. PMID- 11766889 TI - Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease. AB - Pre-eclampsia is a disorder of human pregnancy occurring in 5-10% of all births, and represents the leading cause of infant morbidity and mortality and maternal death. In pre-eclampsia, invasion of fetal trophoblasts into maternal arteries during early pregnancy is shallow or absent. Here we examined the hypothesis that HLA-G, a non-classical class I HLA expressed in cytotrophoblasts, may act as a key gene in pre-eclampsia. We analysed HLA-G at the level of transcription and genotyped a silent CAC-CAT polymorphism in exon 3 and a 14-bp insertion/deletion in the 3' untranslated region. A deficit in levels of the HLA-G3 transcript was observed in mild pre-eclampsia compared to normal placentas. The distribution of HLA-G polymorphisms was different between normal and pre-eclampsia samples. A correlation between the alteration in transcription of the HLA-G gene and certain HLA-G genotypes was also observed. Thus we provide the first evidence for a possible role of HLA-G in genetic susceptibility to, and pathogenesis of pre eclampsia. PMID- 11766890 TI - Ethanol impairs insulin-stimulated mitochondrial function in cerebellar granule neurons. AB - Ethanol impairs insulin-stimulated survival and mitochondrial function in immature proliferating neuronal cells due to marked inhibition of downstream signaling through P13 kinase. The present study demonstrates that, in contrast to immature neuronal cells, the major adverse effect of chronic ethanol exposure (50 mM) in post-mitotic rat cerebellar granule neurons is to inhibit insulin stimulated mitochondrial function (MTT activity, MitoTracker Red fluorescence, and cytochrome oxidase immunoreactivity). Ethanol-impaired mitochondrial function was associated with increased expression of the p53 and CD95 pro-apoptosis genes, reduced Calcein AM retention (a measure of membrane integrity), increased SYTOX Green and propidium iodide uptake (indices of membrane permeability), and increased oxidant production (dihydrorosamine fluorescence and H2O2 generation). The findings of reduced membrane integrity and mitochondrial function in short term (24 h) ethanol-exposed neurons indicate that these adverse effects of ethanol can develop rapidly and do not require chronic neurotoxic injury. A role for caspase activation as a mediator of impaired mitochondrial function was demonstrated by the partial rescue observed in cells that were pre-treated with broad-spectrum caspase inhibitors. Finally, we obtained evidence that the inhibitory effects of ethanol on mitochondrial function and membrane integrity were greater in insulin-stimulated compared with nerve growth factor-stimulated cultures. These observations suggest that activation of insulin-independent signaling pathways, or the use of insulin sensitizer agents that enhance insulin signaling may help preserve viability and function in neurons injured by gestational exposure to ethanol. PMID- 11766891 TI - Characterization of D-fructose transport by rat kidney brush-border membrane vesicles: changes in hypertensive rats. AB - D-fructose transport was characterized in renal brush-border membrane vesicles (BBMVs) from both spontaneously hypertensive rats (SHR) and normotensive genetic control Wistar-Kyoto (WKY) rats. Kinetic studies indicated that the maximal rate (Vmax) of D-fructose transport was significantly lower in SHR compared with WKY rats. No differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. D-fructose inhibited its own transport, whereas the presence of D-glucose, D-galactose, phlorizin, and cytochalasin B did not inhibit the transport of D-fructose in either animal group. To explain the reduction in D-fructose transport in SHR, the density of the D-fructose transporter, GLUT5, was analyzed by Western blot. GLUT5 levels were lower in SHR, a reduction similar to that of the Vmax. Thus, there appears to be a high-affinity, low-capacity, GLUT5-type fructose carrier in the apical membranes of rat kidney cortex, and the decrease in the Vmax of D-fructose transport in renal BBMVs from hypertensive rats correlates well with a reduction in the expression of GLUT5 protein. PMID- 11766892 TI - "Imprints of reality" in the systems mechanisms of brain activity. AB - Pavlov's concepts of the dynamic stereotype - "imprints of reality" - are developed on the basis of the theory of functional systems. Parameters of reality and especially the results of activity satisfying the leading needs of living organisms are dynamically "impressed" in the form of molecular engrams in structures of the results-of-actions acceptors involved in the dominant motivation. The dominant motivation plays the leading role in retrieval of previously formed engrams of the results-of-action acceptors in different functional systems. A general theoretical concept of the emotional and verbal forms of consciousness and their close interaction in humans is developed. PMID- 11766893 TI - Interrelated modification of excitatory and inhibitory connections in the olivocerebellar neural network. AB - A model of plasticity is proposed for the olivocerebellar neural network in which the efficiency of the synaptic inputs to different neurons changes simultaneously and interdependently. This effect is based on the following functional characteristics of the network: simultaneous arrival of an afferent signal via mossy fibers to input granule cells and output neurons in the deep cerebellar nuclei; synchronous arrival of the signal from the inferior olive, via climbing fibers and their collaterals, at cells in the input and output layers, and to Purkinje cells, and the existence of local excitatory, inhibitory, and disinhibitory feedback circuits. Increases (decreases) in post-tetanic Ca2+ concentrations relative to the level evoked by the preceding stimulation in these cells are accompanied by decreases (increases) in the activity of cGMP-dependent protein kinase G, with increases (decreases) in the activity of protein phosphatase I. As a result, dephosphorylation (phosphorylation) of ionotropic receptors is accompanied by simultaneous depression (potentiation) of the excitatory input to a given neuron and potentiation (depression) of the inhibitory input to the same neuron. The depolarizing signal from the inferior olive affects synapse modification in different layers of the network in such a way that its presence (absence) depresses (potentiates) the signal sent from the output cells of the cerebellum to other structures. PMID- 11766894 TI - Characteristics of c-fos gene expression in the brains of rats with different investigative and defensive behaviors. AB - Differences were found in the expression of the c-fos gene in brain structures of rats with "active" and "passive" types of behavior in the open field, hole exploration, and step-down tests. The most marked and intense expression of the c fos gene was seen in "passive" rats. After electrocutaneous stimulation in the step-down test, these animals showed maximum expression of the c-fos gene in most areas of the cerebral cortex, the amygdala, in olfactory structures, the hypothalamus, and the brainstem. In "active" rats in the same conditions, expression of the c-fos gene was seen only in the infralimbic cortex and olfactory nuclei. These results, along with existing data on neurological mapping of the c-fos gene, demonstrate a relationship between the level and topography of c-fos expression, and with typological and, perhaps, individual characteristics of rats. PMID- 11766895 TI - Long-term changes in hippocampus and neocortex EEG spectra in response to pharmacological treatments affecting the cholinergic system. AB - Statistical analysis of EEG spectra averaged over 10-min intervals showed that in rats performing free behavior, peripheral administration of the acetylcholinesterase inhibitor physostigmine induced long-lasting characteristic changes (lasting tens of minutes) in the electrical activity of the dorsal hippocampus (field CAI) and the somatosensory cortex. An increase in the physostigmine dose from 0.05 to 1 mg/kg shifted the peak of the theta rhythm to lower frequencies (3.6-4.9 Hz) without a change in power at this frequency, though there was a decrease in power at 5.7-11.9 Hz. The power of the beta-1 rhythm (13.8-16.4 Hz) was also strongly suppressed. In contrast, the power of the beta-2 rhythm (20.3-26.5 Hz) increased several-fold in a non-linear fashion. Scopolamine suppressed all the changes induced by physostigmine, demonstrating the important role of m-cholinoceptors in changes in EEG spectra. The high dose of physostigmine caused inversion of the power of the beta-2 rhythm: unlike the situation obtaining in controls, the beta-2 power in the hippocampus became significantly greater than that in the neocortex. These data suggest the conclusion that overall significant increases in endogenous acetylcholine levels lead to decreases in the functional activity of the hippocampus and neocortex and that the mechanisms of cholinergic modulation of the theta and beta rhythms are significantly different. It is suggested that conditioned reflex switching, contextual learning, and dissociated sates of memory and consciousness are to a significant extent dependent on long-term changes in the oscillatory activity of the hippocampus and neocortex. PMID- 11766896 TI - Behavioral characteristics of mice with genetic knockout of monoamine oxidase type A. AB - Transgenic mice of line Tg8 were used to study the effects of deletion of the monoamine oxidase type A gene and the absence of the corresponding enzyme on behavior. These experiments showed that Tg8 mice with genetic knockout of monoamine oxidase type A differed from mice of the parental line C3H/HeJ by lower levels of the startle reflex in response to an acoustic signal, while there was no difference in the prestimulus inhibition of the startle response. Tg8 mice showed decreased investigative activity and decreases in the number of sector crossings in the light-dark anxiety test. There were significant increases in aggression as a motivation in male Tg8 mice, which was manifest as an increase in the number of mice demonstrating aggression and a decrease in the latent period of attack. The intensity of aggression changed to a lesser extent - the number of fights even decreased, though longer periods of keeping mice together resulted in increased numbers of deaths among intruder mice. At the same time, there were no significant differences between mice with genetic knockout of monoamine oxidase type A and control mice in terms of the expression of sexual activation: the behavioral responses of Tg8 males to presentation of females was marked and was no different from that of male C3H/HeJ mice. Knockout of the gene had no effect on movement activity on behavior in an elevated cross-shaped maze or in the test for predisposition to catalepsy. PMID- 11766897 TI - The effects of active immunization against plasma amine oxidase on the formation of a conditioned passive avoidance reaction in white rats. PMID- 11766898 TI - Reactive invagination of the neuroepithelium in the rudiments of the neocortex, tectum of the midbrain, and retina of the eye in humans at different stages of development. PMID- 11766899 TI - Features of the structural organization of neuron groups in functionally different zones of the human cerebral cortex from birth to the age of 20 years. PMID- 11766900 TI - Distribution of neuro- and macrogliocytes in layers in different parts of the auditory cortex of the cat brain (quantitative studies). PMID- 11766901 TI - Post-ischemic reorganization of the dendroarchitectonics of field CA3 of the hippocampus of white rats with high levels of convulsive readiness of the brain. PMID- 11766902 TI - Ultrastructure of the main sensory nucleus of the trigeminal nerve of the cat in normal conditions and in conditions of threshold pain stimulation. PMID- 11766903 TI - Sensory neurons and Schwann cells during pharmacological stimulation of a regenerating nerve. PMID- 11766904 TI - Expression of the c-fos gene during emotional stress in rats: the clocking effect of delta sleep-inducing peptide. AB - Emotional stress induced more marked increases in the expression of the c-fos gene in limbo-reticular structures of the brain in rats prognostically predisposed to emotional stress. I.p. doses of delta sleep-inducing peptide (DSIP) (60 nmol/kg) weakened the stress-induced expression of the c-fos gene. This effect was more apparent in animals predisposed to emotional stress, in which preliminary injections decreased stress-induced c-fos expression in the paraventricular hypothalamus and the medial and lateral parts of the septum. The decreased expression of the early gene c-fos in emotional stress after preliminary dosage with DSIP may reflect the leading mechanism of the anti-stress action of this peptide. PMID- 11766905 TI - Changes in neuron activity in the dorsolateral part of the pons during stimulation of areas of the brainstem inhibiting movement and muscle tone. AB - Changes in the activity of 44 neurons in the mesencephalic locomotor region and 38 neurons in the pontine inhibitory zone were recorded during stimulation of the gigantocellular reticular nucleus and the dorsal part of the oral reticular nucleus of the pons, which evokes inhibition of rigid tone in the hindlimbs of decerebrate rats. Decreases in muscle tone were always accompanied by decreases in the spike frequency of neurons in the mesencephalic locomotor region and increases in the activity of neurons in the pontine inhibitory zone. It is suggested that stimulation of the inhibitory parts of the brainstem simultaneously activates the reticulospinal inhibitory system, hyperpolarizing spinal alpha-motoneurons, and inhibits the neuron population of the mesencephalic locomotor region, which relates to the induction of locomotion and muscle tone. PMID- 11766906 TI - Ontogenetic formation of the ability of rats to count time endogenously and its relationship with the level of anxiety. AB - Improvements in the ability to count time endogenously with maturation in rats depends on the normal age dynamics of anxious-phobic state and is associated with the state of the peripheral compartment of the sympatheticoadrenal system. Increases in the lengths of locomotive excursions were accompanied by decreases in anxious-phobic state and increases in the quality of time-keeping. In rats aged three and six months (but not in one-month-old rats), the ability to count time endogenously showed a parabolic relationship with initial anxious-phobic state: the most precise and efficient counting of time intervals needs a certain intermediate level of anxiety, covering a relatively narrow range. Anxious-phobic states beyond this optimum, either increases or decreases, lead to degradation of chronometric ability. PMID- 11766908 TI - Trends in diet, nutritional status, and diet-related noncommunicable diseases in China and India: the economic costs of the nutrition transition. AB - Undernutrition is being rapidly reduced in India and China. In both countries the diet is shifting toward higher fat and lower carbohydrate content. Distinct features are high intakes of foods from animal sources and edible oils in China, and high intakes of dairy and added sugar in India. The proportion of overweight is increasing very rapidly in China among all adults; in India the shift is most pronounced among urban residents and high-income rural residents. Hypertension and stroke are relatively higher in China and adult-onset diabetes is relatively higher in India. Established economic techniques were used to measure and project the costs of undernutrition and diet-related noncommunicable diseases in 1995 and 2025. Current WHO mortality projections of diet-related noncommunicable diseases, dietary and body composition survey data, and national data sets of hospital costs for healthcare, are used for the economic analyses. In 1995, China's costs of undernutrition and costs of diet-related noncommunicable diseases were of similar magnitude, but there will be a rapid increase in the costs and prevalence of diet-related noncommunicable diseases by 2025. By contrast with China, India's costs of undernutrition will continue to decline, but undernutrition costs did surpass overnutrition diet-related noncommunicable disease costs in 1995. India's rapid increase in diet-related noncommunicable diseases and their costs projects similar economic costs of undernutrition and overnutrition by 2025. PMID- 11766907 TI - The sensitivity of neurons in the lateral geniculate body of the cat to the orientation vectors of brightness gradients. AB - We describe here a new property of visual neurons: sensitivity to the magnitude and orientation of the brightness gradient vector in a test stimulus presented in the receptive field of the neuron. The brightness gradient test image was a spot (diameter 4 degrees) on the dark background of the slide. Brightness changed linearly within the spot. The absolute value of the brightness gradient varied over the range 0.4-2.7 cd/m2 /degrees in the direction of the brightness gradient. The integral brightness in the test spot containing the gradient image was identical for different values of the brightness gradient. The numbers of spikes in the on- and off-responses of on and off neurons in the lateral geniculate body of cats depended on the orientation of the brightness gradient vector in the test stimulus. The sensitivity of neurons to the orientation of the brightness gradient vector, K (the coefficient of sensitivity), was assessed as the normalized difference between the number of spikes in neuron responses in the preferred and non-preferred orientations of the brightness gradient vector in the neuron's receptive field. The mean sensitivity coefficient for 53 cells was 0.55 +/- 0.20. A 6.7-fold decrease in the brightness gradient resulted in a 3.7-fold decrease in the coefficient of sensitivity (for the preferred direction of the orientation of the gradient vector); there was no change in the latent period of responses. The preferred orientation of the brightness gradient vector in the receptive fields of neurons coincided (to within +/-22.5 degrees) with the radial direction on the map of the field of vision in 45% of cases, and with the tangential direction in 26% of cells. PMID- 11766909 TI - Retinoic acid homeostasis: retinoic acid regulates liver retinol esterification as well as its own catabolic oxidation in liver. AB - Retinol is stored in liver in the form of its esters. The retinol-esterifying enzyme lecithin:retinol acyltransferase (LRAT) catalyzes the conversion of retinol into its storage form. Expression of the LRAT mRNA is induced by retinoic acid (RA), or by dietary vitamin A, and is downregulated upon vitamin A depletion. RA also induces the expression in liver of the mRNA for CYP26, the enzyme that disposes of excess RA by oxidizing RA to 4-oxo-RA. CYP26 is downregulated upon vitamin A depletion. PMID- 11766910 TI - Vegetables, fruits, and colorectal cancer risk: what should we believe? AB - Among dietary factors implicated in the development of colorectal cancer (CRC), the inverse relationship between vegetable and fruit consumption and CRC risk has long been believed to represent the strongest epidemiologic evidence. However, recently published large prospective studies have produced conflicting results and the results of one randomized intervention human trial do not support the protective role of vegetable and fruit consumption in colorectal carcinogenesis. Conflicting data with regard to the effect of dietary factors, including vegetables and fruits, on CRC risk likely reflect inherent, probably irresolvable, limitations of currently available tools to detect a real beneficial or harmful effect associated with these factors. PMID- 11766911 TI - Cognitive skill acquisition and transfer in younger and older adults. AB - The acquisition of cognitive skills often depends on 1 of (or a combination of) 2 processes, the execution of an algorithm, and the retrieval of problem instances. This study examined the effects of age and repetition of problem instances on the production and verification of solutions to 2 serially presented sets of alphabet arithmetic problems. Analyses of the parameters derived from power-function fits for individuals revealed age differences favoring young adults in improvement span, learning rate, and asymptote. For both age groups, the beneficial effects of repetitions on 1st-set response times were attributable to algorithmic speedup and to the retrieval of instances, whereas improvements in the speed of 2nd-set response times were attributable primarily to item retrieval. PMID- 11766912 TI - Examining age differences in performance of a complex information search and retrieval task. AB - This study examined age differences in performance of a complex information search and retrieval task by using a simulated real-world task typical of those performed by customer service representatives. The study also investigated the influence of task experience and the relationships between cognitive abilities and task performance. One hundred seventeen participants from 3 age groups, younger (20-39 years). middle-aged (40-59 years), and older (60-75 years), performed the task for 3 days. Significant age differences were found for all measures of task performance with the exception of navigational efficiency and number of problems correctly navigated per attempt. There were also effects of task experience. The findings also indicated significant direct and indirect relations between component cognitive abilities and task performance. PMID- 11766913 TI - Influence of stimulus repetition on negative priming. AB - Potential age-related differences in the influence of stimulus repetition on negative and positive priming were investigated in a same-different picture comparison task. Forty-eight young adults and 48 old adults compared a target picture of a familiar object with a standard picture of a familiar object to determine if they were the same or different, while ignoring an overlapping distractor picture presented in a different color. Negative priming effects increased in magnitude with the repetition of the experimental stimuli in a similar fashion for both young and old adults. Conversely, positive priming effects decreased in magnitude with increases in stimulus repetition for both young and old adults. These data suggest that identity-based inhibition develops in a similar fashion from young adulthood to old age. Furthermore, these data add to the growing body of studies that suggest age invariance in the ability to inhibit task-irrelevant information in the environment on the basis of stimulus identity. PMID- 11766914 TI - The "common cause hypothesis" of cognitive aging: evidence for not only a common factor but also specific associations of age with vision and grip strength in a cross-sectional analysis. AB - A prominent hypothesis in cognitive aging is the existence of a common factor that is responsible for age-related deterioration in cognitive and noncognitive processes. A multiple indicators, multiple causes model was used to examine the nature of this common factor and its relationship to age, gender, and the apolipoprotein E (APOE) genotype. The common factor was modeled by using 10 indicator variables with 374 participants aged between 77.4 and 98.7 years. A latent factor was identified, with all indicators except blood pressure loading significantly. This factor could be established in 2 age strata within the sample. After controlling for the effects of gender, APOE, and level of education, direct effects of age were seen on visual functioning and grip strength. APOE was significantly associated with memory but not with the common factor. The findings suggest that a number of specific processes may operate concurrently with any common cause factor. PMID- 11766915 TI - Longitudinal change in language production: effects of aging and dementia on grammatical complexity and propositional content. AB - Mixed modeling was used to examine longitudinal changes in linguistic ability in healthy older adults and older adults with dementia. Language samples, vocabulary scores, and digit span scores were collected annually from healthy older adults and semiannually from older adults with dementia. The language samples were scored for grammatical complexity and propositional content. For the healthy group, age-related declines in grammatical complexity and propositional content were observed. The declines were most rapid in the mid 70s. For the group with dementia, grammatical complexity and propositional content also declined over time, regardless of age. Rates of decline were uniform across individuals. These analyses reveal how both grammatical complexity and propositional content are related to late-life changes in cognition in healthy older adults aswell as those with dementia. Alzheimer's disease accelerates this decline, regardless of age. PMID- 11766916 TI - Current-events knowledge in adults: an investigation of age, intelligence, and nonability determinants. AB - This study expanded the scope of knowledge typically included in intellectual assessment to incorporate domains of current-events knowledge from the 1930s to the 1990s across the areas of art/humanities, politics/economics, popular culture, and nature/science/technology. Results indicated that age of participants was significantly and positively related to knowledge about current events. Moreover, fluid intelligence was a less effective predictor of knowledge levels than was crystallized intelligence. Personality (i.e. Openness to Experience) and self-concept were also positively related to current-events knowledge. The results are consistent with an investment theory of adult intellect, which views development as an ongoing outcome of the combined influences of intelligence-as-process, personality, and interests, leading to intelligence-as-knowledge (P. L. Ackerman, 1996b). PMID- 11766917 TI - Motivation and representational processes in adulthood: the effects of social accountability and information relevance. AB - The role of motivation in determining age differences in social representations was examined. Adults aged 20 to 83 years were given an impression formation task that attempted to manipulate motivation by varying the characteristics of the target and the extent to which participants would be held accountable for their impressions. It was hypothesized that increasing age would be associated with greater selectivity in the use of available cognitive resources to support the construction of accurate representations. Support for this hypothesis was obtained when trait inferences and recall were examined. Specifically, older adults made more accurate trait inferences and recalled more information when the target was similar in age or they were held accountable for their impressions. In contrast, younger adults demonstrated similar levels of accuracy across conditions. The fact that these effects were observed when cognitive resources was controlled suggests a motivational effect that is independent of age differences in cognitive ability. PMID- 11766918 TI - Self-concept differentiation across the adult life span. AB - This study used 2 measures to examine 158 adults' (80 men, 78 women; ages 20 to 88 years) self-concept differentiation (SCD) across 5 role-specific self representations. Findings revealed that the 2 measures did not assess SCD in similar ways and that they showed different associations with age. Specifically, the 1st measure was not significantly related to age, whereas the 2nd measure showed a curvilinear, U-shaped association with age. The 2nd SCD index also showed significant associations with several measures of emotional adjustment and 6 dimensions of psychological well-being. Additional analyses showed that age moderated the associations between SCD and positive and negative psychological well-being. A high level of SCD was associated with lower positive and higher negative psychological well-being for both young and older adults. However, this effect was significantly more pronounced in older adults. PMID- 11766919 TI - Widowhood and illness: a comparison of social network characteristics in France, Germany, Japan, and the United States. AB - This study examined social network characteristics of adults aged 70 to 90 years in relation to widowhood and illness in France, Germany, Japan, and the United States. Participants were drawn from representative samples from each of the 4 countries (total N = 1,331). Resource deficit profiles based on whether respondents were widowed, ill, both, or neither were directly related to social network characteristics for German and Japanese adults, were differentially related by gender and age for French adults, and were not related to social networks of Americans. Country, gender, and age differences in total network size, proportion of close network members, and frequency of contact with network members are reported. Similarities and differences found in the associations between normative late-life deficits and social network characteristics in the 4 countries point to the importance of investigating sociocultural factors that mediate the impact of resource loss and afford life quality in very old age. PMID- 11766920 TI - Aging and interference in verbal working memory. AB - According to inhibitory views of working memory, old adults should have particular problems deleting irrelevant information from working memory, leading to greater interference effects compared with young adults. The authors investigated this hypothesis by using variations of an A-B, C-D retroactive interference paradigm in working memory with young and old adults. They used a recognition measure of memory, assessing both accuracy and reaction time. The primary finding was that senior adults consistently exhibited proportionally greater retroactive interference effects compared with young adults when interfering word pairs that had been read aloud had to be rejected. Patterns of recognition and reaction time data suggested that old adults' activation of target material is similar to young adults, but they experience sustained activation of irrelevant material that has entered working memory. Theoretical implications of these findings for inhibitory deficit (R. T. Zacks & L. Hasher, 1998) and source memory deficit accounts of cognitive aging are discussed. PMID- 11766921 TI - Influences on the efficiency of prospective memory in younger and older adults. AB - The influence of 4 factors on age-related declines in prospective memory (PM) was considered in 2 experiments. The results of the experiments reveal that age related differences in PM were not moderated by the degree of match between the nature of processing required in the ongoing activity and the defining features of the PM cue. Age-related differences in the accuracy of PM responses were primarily attributable to an increase in the number of omission errors committed by older adults. Age-related differences in PM were somewhat independent of the ability to recall the PM cues and intentions following task performance and were mediated by the cognitive resources of processing speed, inhibitory control, and working memory. PMID- 11766922 TI - Instructional manipulations and age differences in memory: now you see them, now you don't. AB - The instructions for most explicit memory tests use language that emphasizes the memorial component of the task. This language may put older adults at a disadvantage relative to younger adults because older adults believe that their memories have deteriorated. Consequently, typical explicit memory tests may overestimate age-related decline in cognitive performance. In 2 experiments, older and younger adults performed a memory test on newly learned trivia. In both experiments, age differences were obtained when the instructions emphasized the memory component of the task (memory emphasis) but not when the instructions did not emphasize memory (memory neutral). These findings suggest that aspects of the testing situation. such as experimental instructions, may exaggerate age differences in memory performance and need to be considered when designing studies investigating age differences in memory. PMID- 11766923 TI - Age differences in coping and locus of control: a study of managerial stress in Hong Kong. AB - The present study involved data collection from 3 samples of Hong Kong managers to examine mechanisms by which age would relate to work well-being. A total of 634 managers was drawn by random sampling and purposive sampling methods. The results showed that age was positively related to well-being (job satisfaction and mental well-being). Furthermore, older managers reported fewer sources of stress, better coping, and a more internal locus of control. Multiple regression analyses suggested that the relations of age with 2 well-being indicators can be attributed to various combinations of coping, work locus of control, sources of stress, managerial level, and organizational tenure. PMID- 11766924 TI - Two-handed performance of a rhythmical fitts task by individuals and dyads. AB - The authors investigated 4 variants of a reciprocal Fitts task in which the pointer was moved to a stationary target, the target was moved to a stationary pointer, or both the pointer and the target were moved to each other bimanually; the bimanual task was carried out either by a single person or by a dyad. Fitts's law held in all 4 conditions, with only minor parametric changes. The kinematic organization varied with task difficulty but remained invariant in task space (i.e., in the mutual frame of reference of the pointer-target system) whatever the pointing condition. In the bimanual conditions, the 2 effectors were coordinated in antiphase with compensatory variability. The authors suggest that the observed chronometric and kinematic patterns emerge from an interplay between simple harmonic motion and the stabilizing influence of the informational flow generated by the closing of the gap between the pointer and the target interval. PMID- 11766925 TI - New objects dominate luminance transients in setting attentional priority. AB - Both the sudden appearance of an object and sudden changes in existing object features influence priority in visual search. However, direct comparisons of these influences have not been made under controlled conditions. In 5 visual search experiments, new object onsets were compared directly with changes in the luminance of old objects. Factors included the luminance contrast of items against the background, the magnitude of luminance change, and the probability that these changes were associated with the target item. New objects were consistently more effective in guiding search, such that a new item with very low luminance contrast was equivalent to an old item undergoing a large change in luminance. An important exception was an old item changing in contrast and polarity, which was as effective as the appearance of a new object. This indicates that search priority is biased toward object rather than situational changes. PMID- 11766926 TI - A dynamical framework to understand performance trade-offs and interference in dual tasks. AB - This study demonstrated that the dynamic pattern approach may reconcile resource and outcome conflict theories to explain performance in dual tasks. Participants performed a bimanual coordination task and a reaction time task with different conditions of attentional priority. Results showed a trade-off between pattern variability and reaction time when priority was given to the coordination task. Such a trade-off was indicative of resource allocation. An analysis of perturbation in the bimanual coordination revealed interference, a reputed sign of outcome conflict. Moreover, interference diminished substantially when priority was given to the bimanual task. The coexistence of performance trade-off and outcome conflict suggests that these two phenomena are not mutually exclusive. Rather, both may follow from modifying the coupling between the limbs through attention. PMID- 11766927 TI - Accommodation, occlusion, and disparity matching are used to guide reaching: a comparison of actual versus virtual environments. AB - The authors used a virtual environment to investigate visual control of reaching and monocular and binocular perception of egocentric distance, size, and shape. With binocular vision, the results suggested use of disparity matching. This was tested and confirmed in the virtual environment by eliminating other information about contact of hand and target. Elimination of occlusion of hand by target destabilized monocular but not binocular performance. Because the virtual environment entails accommodation of an image beyond reach, the authors predicted overestimation of egocentric distances in the virtual relative to actual environment. This was confirmed. The authors used -2 diopter glasses to reduce the focal distance in the virtual environment. Overestimates were reduced by half. The authors conclude that calibration of perception is required for accurate feedforward reaching and that disparity matching is optimal visual information for calibration. PMID- 11766928 TI - Disengaging attention: on the locus of the cue-duration effect in partial report. AB - Increasing cue duration impairs performance in bar-probe partial report when cues are presented peripherally, but not centrally (P. Dixon, R. Gordon, A. Leung, & V. Di Lollo, 1997). Three experiments examined whether this cue-duration effect reflects processes of exogenous attention. The effect of cue duration on partial report performance with peripheral, but not central, cues was replicated (Experiment 1). Further experiments manipulated the degree that exogenous versus endogenous modes of selection were favored and found that the cue-duration effect for peripheral cues was reduced (a) when blocks contained a high proportion of central cues (Experiment 2) and (b) when the color of the cue indicated the location of the target (Experiment 3). These findings challenge the view that the cue-duration effect is restricted to exogenous attention and are discussed in terms of the process of disengaging attention from the cue to reallocate attention to the target representation. PMID- 11766929 TI - Toward a unified fielder theory: what we do not yet know about how people run to catch a ball. AB - Linear optic trajectory theory claims that people catch balls by running in a direction that keeps an optic trajectory of the ball linear. The authors show a range of ball trajectories for which departures of the optic trajectory from linearity do not predict which direction people will run, and the direction they choose does not correct these departures. Data from a wide range of ball trajectories show that people run so that the angle of elevation of gaze to the ball increases at a decreasing rate. But it is not yet known why people choose the particular path they do from the many that would achieve this. PMID- 11766930 TI - Effect of object onset on the distribution of visual attention. AB - There now exists considerable evidence to suggest that the appearance of a new object in the visual field captures visual attention. One of the consequences of this attentional capture is that the object initiates a redistribution of attentional resources across visual space. This is classically observed in the precuing paradigm in which the onset of an abrupt cue influences the processing of a subsequently presented target. The present research describes a new phenomenon that occurs as a result of a new object appearing in the visual field. A stimulus presented in a region of space adjacent to a corner of an onsetting object receives an enhancement of processing relative to a stimulus presented adjacent to one of the object's straight edges. With the use of 2 converging methods, evidence is presented that suggests that the effect is a higher order attentional phenomenon whereby greater resources become directed to the corners of objects. PMID- 11766931 TI - Hemispheric asymmetries for global and local visual perception: effects of stimulus and task factors. AB - Although neurotogical and physiological studies indicate a right hemisphere superiority in global processing and a left hemisphere superiority in local processing of Navon-type hierarchical letters (D. Navon, 1977), most investigations of lateralized perception in healthy participants report neither asymmetry. In 6 experiments the authors examined the influence of attentional demands, stimulus properties, and mode of response on perceptual asymmetries for global and local perception. Consistent with their theoretical predictions, asymmetries were more robust on divided- than focused-attention tasks and in response to stimuli in which local and global levels were equally salient compared with those with greater global than local saliency. Contrary to their prediction, perceptual asymmetries were not influenced by the complexity of the motor response. PMID- 11766932 TI - Effects of horizontal viewing angle on visual and audiovisual speech recognition. AB - The authors investigated the effects of changes in horizontal viewing angle on visual and audiovisual speech recognition in 4 experiments, using a talker's face viewed full face, three quarters, and in profile. When only experimental items were shown (Experiments 1 and 2), identification of unimodal visual speech and visual speech influences on congruent and incongruent auditory speech were unaffected by viewing angle changes. However, when experimental items were intermingled with distractor items (Experiments 3 and 4), identification of unimodal visual speech decreased with profile views, whereas visual speech influences on congruent and incongruent auditory speech remained unaffected by viewing angle changes. These findings indicate that audiovisual speech recognition withstands substantial changes in horizontal viewing angle, but explicit identification of visual speech is less robust. Implications of this distinction for understanding the processes underlying visual and audiovisual speech recognition are discussed. PMID- 11766933 TI - Switching between simple cognitive tasks: the interaction of top-down and bottom up factors. AB - How do top-down factors (e.g., task expectancy) and bottom-up factors (e.g., task recency) interact to produce an overall level of task readiness? This question was addressed by factorially manipulating task expectancy and task repetition in a task-switching paradigm. The effects of expectancy and repetition on response time tended to interact underadditively, but only because the traditional binary task-repetition variable lumps together all switch trials, ignoring variation in task lag. When the task-recency variable was scaled continuously, all 4 experiments instead showed additivity between expectancy and recency. The results indicated that expectancy and recency influence different stages of mental processing. One specific possibility (the configuration-execution model) is that task expectancy affects the time required to configure upcoming central operations, whereas task recency affects the time required to actually execute those central operations. PMID- 11766934 TI - Attentional momentum does not underlie the inhibition of return effect. AB - J. Pratt, T. M. Spalek, and F. Bradshaw (1999) recently proposed that attentional momentum is the mechanism underlying the inhibition of return (IOR) effect. They suggested that momentum associated with an attentional movement away from a peripherally cued location and toward an uncued opposite location is essential and fundamental to the finding of an IOR effect. Although it is clear from the present study and from a reanalysis of data from Pratt et al. that response time can be facilitated at an uncued opposite location, this putative effect of attentional momentum is neither robust nor reliable. First, it occurs for only a minority of participants. Second, it occurs in only a subset of the cued display positions. And finally, it is uncorrelated with the occurrence of IOR. Together the data indicate that the attentional momentum hypothesis is an overgeneralization and that it does not underlie the robust and reliable IOR effect. PMID- 11766935 TI - Attentional consequences of object appearance and disappearance. AB - This study compared the attentional effects of object appearances (onsets) and disappearances (offsets) in moderately complex displays. Four experiments showed that onsets produce the inhibition of return (IOR) effect that has been found with simpler displays. In contrast, although offsets did produce inhibitory effects, these effects did not follow the spatial or temporal pattern of IOR. Two further experiments used a very salient object disappearance to determine whether the typical pattern for IOR could be instantiated; it was not. The results indicate that object appearances are more potent perceptual events than object disappearances. In addition, object disappearances have different attentional consequences than object appearances: Disappearances provoke earlier and spatially narrower inhibition. The results are consistent with the view that inhibition serves a functional role in increasing the efficiency of visual search processes. PMID- 11766936 TI - A model of the formation of illusory conjunctions in the time domain. AB - The authors present a model to account for the miscombination of features when stimuli are presented using the rapid serial visual presentation (RSVP) technique (illusory conjunctions in the time domain). It explains the distributions of responses through a mixture of trial outcomes. In some trials, attention is successfully focused on the target, whereas in others, the responses are based on partial information. Two experiments are presented that manipulated the mean processing time of the target-defining dimension and of the to-be-reported dimension, respectively. As predicted, the average origin of the responses is delayed when lengthening the target-defining dimension, whereas it is earlier when lengthening the to-be-reported dimension; in the first case the number of correct responses is dramatically reduced, whereas in the second it does not change. The results, a review of other research, and simulations carried out with a formal version of the model are all in close accordance with the predictions. PMID- 11766937 TI - Seeing two sides at once: effects of viewpoint and object structure on recognizing three-dimensional objects. AB - Five experiments demonstrated that adults can identify certain novel views of 3 dimensional model objects on the basis of knowledge of a single perspective. Geometrically irregular contour (wire) and surface (clay) objects and geometrically regular surface (pipe) objects were accurately recognized when rotated 180 degrees about the vertical (y) axis. However, recognition accuracy was poor for all types of objects when rotated around the y-axis by 90 degrees. Likewise, more subtle rotations in depth (i.e., 30 degrees and 60 degrees) induced decreases in recognition of both contour and surface objects. These results suggest that accurate recognition of objects rotated in depth by 180 degrees may be achieved through use of information in objects' 2-dimensional bounding contours, the shapes of which remain invariant over flips in depth. Consistent with this interpretation, a final study showed that even slight rotations away from 180 degrees cause precipitous drops in recognition accuracy. PMID- 11766938 TI - Brief bimanual force pulses: correlations between the hands in force and time. AB - Three experiments assessed coupling phenomena in the coordination of bimanual force pulses. Experiment 1 required symmetric force pulses (equal target forces and rise times for both hands) using the index finger of each hand. As the authors expected, on the basis of bimanual pointing movement results, this experiment revealed positive correlations between both the force rise times and the force amplitudes of the two hands. Experiments 2 and 3 included asymmetric conditions with different target force amplitudes (Experiment 2) or target rise times (Experiment 3). In Experiment 2 force amplitudes but not rise times were fully decoupled in the asymmetric condition. In the asymmetric condition of Experiment 3, however, neither rise times nor force amplitudes were fully decoupled. The results suggest a hierarchical control structure with temporal control dominating nontemporal control of bimanual force coordination. PMID- 11766939 TI - Hierarchical categorization of coarticulated phonemes: a theoretical analysis. AB - This article is concerned with the question of how listeners recognize coarticulated phonemes. The problem is approached from a pattern classification perspective. First, the potential acoustical effects of coarticulation are defined in terms of the patterns that form the input to a classifier. Next, a categorization model called HICAT is introduced that incorporates hierarchical dependencies to optimally deal with this input. The model allows the position, orientation, and steepness of one phoneme boundary to depend on the perceived value of a neighboring phoneme. It is argued that, if listeners do behave like statistical pattern recognizers, they may use the categorization strategies incorporated in the model. The HICAT model is compared with existing categorization models, among which are the fuzzy-logical model of perception and Nearey's diphone-biased secondary-cue model. Finally, a method is presented by which categorization strategies that are likely to be used by listeners can be predicted from distributions of acoustical cues as they occur in natural speech. PMID- 11766940 TI - The independence of size perception and distance perception. AB - Research on distance perception has focused on environmental sources of information, which have been well documented; in contrast, size perception research has focused on familiarity or has relied on distance information. An analysis of these two parallel bodies of work reveals their lack of equivalence. Furthermore, definitions of familiarity need environmental grounding, specifically concerning the amount of size variation among different tokens of an object. To demonstrate the independence of size and distance perception, subjects in two experiments were asked to estimate the sizes of common objects from memory and then to estimate both the sizes and the distances of a subset of such objects displayed in front of them. The experiments found that token variation was a critical variable in the accuracy of size estimations, whether from memory or with vision, and that distance had no impact at all on size perception. Furthermore, when distance information was good, size had no effect on distance estimation; in contrast, at far distances, the distances to token variable or unknown objects were estimated with less accuracy. The results suggest that size perception has been misconceptualized, so that the relevant research to understand its properties has not been undertaken. The size-distance invariance hypothesis was shown to be inadequate for both areas of research. PMID- 11766941 TI - Time-to-passage judgments on circular trajectories are based on relative optical acceleration. AB - Current theories of arrival time have difficulty explaining performance in the common but neglected case of nonlinear approach. Global tau, a variable supposed to guide time-to-passage (TTP) judgments of objects approaching on linear trajectories, does not apply to circular movement. However, TTP judgments are surprisingly accurate in such cases. We simulated movement through a three dimensional cloud of point-lights on various circular trajectories. Arrival-time judgments were found to be above chance when observers had to determine which of two expansionless targets would pass them first. Similar to the inside bias observed in heading studies on circular trajectories, observers showed a strong bias to select the target on the inside of their own curved motion path as passing by first. Analysis of the projected target motion revealed that targets on the inside had lower optical velocities and relatively high optical acceleration rates. Empirical TTP judgments agreed best with a strategy based on relative optical velocity changes. PMID- 11766942 TI - Bayesian contour integration. AB - The process by which the human visual system parses an image into contours, surfaces, and objects--perceptual grouping--has proven difficult to capture in a rigorous and general theory. A natural candidate for such a theory is Bayesian probability theory, which provides optimal interpretations of data under conditions of uncertainty. But the fit of Bayesian theory to human grouping judgments has never been tested, in part because methods for expressing grouping hypotheses probabilistically have not been available. This paper presents such methods for the case of contour integration--that is, the aggregation of a sequence of visual items into a "virtual curve." Two experiments are reported in which human subjects were asked to group ambiguous configurations of dots (in Experiment 1, a sequence of five dots could be judged to contain a "corner" or not; in Experiment 2, an arrangement of six dots could be judged to fall into two disjoint contours or one smooth contour). The Bayesian theory accounts extremely well for subjects' judgments, explaining more than 75% of the variance in both tasks. The theory thus provides a far more quantitatively precise account of human contour integration than has been previously possible, allowing a very precise calculation of the subjective goodness of a virtual chain of dots. Because Bayesian theory is inferentially optimal, this finding suggests a "rational justification," and hence possibly an evolutionary rationale, for some of the rules of perceptual grouping. PMID- 11766943 TI - Separating perceptual processes from decisional processes in identification and categorization. AB - Four observers completed perceptual matching, identification, and categorization tasks using separable-dimension stimuli. A unified quantitative approach relating perceptual matching, identification, and categorization was proposed and tested. The approach derives from general recognition theory (Ashby & Townsend, 1986) and provides a powerful method for quantifying the separate influences of perceptual processes and decisional processes within and across tasks. Good accounts of the identification data were obtained from an initial perceptual representation derived from perceptual matching. The same perceptual representation provided a good account of the categorization data, except when selective attention to one stimulus dimension was required. Selective attention altered the perceptual representation by decreasing the perceptual variance along the attended dimension. These findings suggest that a complete understanding of identification and categorization performance requires an understanding of perceptual and decisional processes. Implications for other psychological tasks are discussed. PMID- 11766944 TI - Divided attention between lyrics and tunes of operatic songs: evidence for independent processing. AB - Excerpts from French operatic songs were used to evaluate the extent to which language and music compete for processing resources. Do these two dimensions conflict? Are they integrated into a single percept? Or are they independent? The final word of each excerpt was either semantically congruous or incongruous relative to the prior linguistic context and was sung either in or out of key. Participants were asked to detect either the semantic or the melodic incongruity (single task) or both (dual task). We predicted a dual-task deficit if these tasks conflicted and no deficit if they were either independent or integrated. In order to distinguish between these last two outcomes, trial-by-trial contingency analyses were also computed, predicting no correlation if the tasks were conflicting or independent, a positive correlation under the assumption of integration and a negative correlation if dividing attention is impossible. Our results show similar levels of performance in single and dual tasks and no correlation between dual-task judgments, thus suggesting that semantic and melodic aspects of language are processed by independent systems. In addition, a comparison between musicians and nonmusicians shows that these conclusions are independent of musical expertise. PMID- 11766945 TI - Discriminating time intervals presented in sequences marked by visual signals. AB - This article presents the results of three experiments on the discrimination of time intervals presented in sequences marked by brief visual signals. In Experiment 1A (continuous condition), the participants had to indicate whether, in a series of 2-4 intervals marked by 3-5 visual signals, the last interval was shorter or longer than the previous one(s). In Experiment 1B (discontinuous condition), the participants indicated whether, in a presentation of two series of 1-3 intervals, with each series being marked by 2-4 signals, the intervals of the second sequence were shorter or longer than those of the first. Whenever one, two, or three standard intervals were presented, the difference threshold was as high at 150 msec as it was at 300 msec with the continuous method but increased monotonically from 150 to 900 msec with the discontinuous method. With both methods, the increase was well described by Weber's law--the Weber fraction was roughly constant--between 600 and 900 msec (Experiment 2), whereas between 900 and 1,200 msec (Experiment 3), the Weber fraction increased. PMID- 11766946 TI - Processing demand modulates the effects of spatial attention on the judged duration of a brief stimulus. AB - How does attention influence the judged duration of a brief stimulus? In the four experiments reported here, we show that the effect of spatial attention on duration judgment depends on the processing demand of the concurrent nontemporal task. When participants had to perform a speeded letter discrimination task in addition to duration rating, the judged duration was longer at a cued location than at an uncued location, regardless of whether the cue was exogenous or endogenous. However, when the same stimuli were presented but no concurrent nontemporal task was required, duration was judged to be shorter at the cued location, as compared with the uncued locations. Furthermore, although spatial attention influenced duration judgment, no object-based attentional effects were found. These findings suggest that, although spatial attention plays an important role in the judged duration of a briefly presented stimulus, its effect is mediated by the processing demand of the task. PMID- 11766947 TI - Attentional guidance of the eyes by contextual information and abrupt onsets. AB - Contextual cuing is a memory-based phenomenon in which previously encountered global pattern information in a display can automatically guide attention to the location of a target (Chun & Jiang, 1998), leading to rapid and accurate responses. What is not clear is how contextual cuing works. By monitoring eye movements, we investigated the roles that recognition and guidance play in contextual cuing. Recognition does not appear to occur on every trial and sometimes does not have its effects until later in the search process. When recognition does occur, attention is guided straight to the target rather than in the general direction. In Experiment 2, we investigated the interaction between memory-driven search (contextual cuing) and stimulus-driven attentional capture by abrupt onsets. Contextual cuing was able to override capture by abrupt onsets. In contrast, onsets had almost no effect on the degree of contextual cuing. These data are discussed in terms of the role of top-down and bottom-up factors in the guidance of attention in visual search. PMID- 11766948 TI - Attentional capture by globally defined objects. AB - The abrupt appearance of a new perceptual object in the visual field typically captures visual attention. However, if attention is focused in advance on a different location, onsets can fail to capture attention (Yantis & Jonides, 1990). In the present experiments, we investigated the extent to which the deployment of attention to the local level of a hierarchical scene may be affected by the abrupt appearance of a new object at the global level. Participants searched for a semi-disk target in an array of randomly oriented segmented disks ("pacmen"). On half the trials, a subset of the segmented disks induced a subjective square. On these critical trials, participants were significantly slower to respond to the presence of a local target even though the local features of the display were qualitatively identical across all conditions. This slowing was absent when outline pacmen were used (which do not induce subjective figures) and when the subjective square was perceptually old. When the participants' task was defined at the global level of the display, a new local element failed to capture attention, suggesting an asymmetry in the ability of objects at different levels of a hierarchical scene to capture attention. In a control experiment, a new local element captured attention, however, when the participants' task was defined at the local level, indicating that the local item was in principle capable of capturing attention. It is argued that global objects capture attention because they convey important information about the environment that is not available at the local level. PMID- 11766949 TI - Asymmetrical contrast effects induced by luminance and color configurations. AB - In the two experiments, the use of a psychophysical procedure of brightness/darkness cancellation shed light on interactions between spatial arrangement and figure-ground contrast in the perceptual filling in of achromatic and colored surfaces. Achromatic and chromatic Kanizsa squares with varying contrast, contrast polarity, and inducer spacing were used to test how these factors interact in the perceptual filling in of surface brightness or darkness. The results suggest that the neuronal processing of surfaces with apparent contrast, leading to figure-ground segregation (i.e., perceptual organization), is governed by mechanisms that integrate both luminance contrast and spatial information carried by the inducing stimuli, while discarding information on contrast polarity or color. The findings are discussed in relation to earlier observations on brightness assimilation and contrast. They support theories of nonantagonistic neural mechanisms suppressing local contrast or color signs in brightness-based figure-ground percepts. Such mechanisms might be necessary to cancel potentially conflicting polarities in geometrically complex visual stimuli so that perceptual filling in resulting in the most plausible representation of figure and ground can be achieved. PMID- 11766950 TI - On the use of metacontrast to assess magnocellular function in dyslexic readers. AB - It has been proposed that dyslexia is the result of a deficit in the magnocellular system. Reduced metacontrast masking in dyslexic readers has been taken as support for this view. In metacontrast, a masking stimulus reduces the visibility of a spatially adjacent target stimulus when the target stimulus precedes the masking stimulus by about 30-100 msec. Recent evidence indicates that the latency difference between the magnocellular and parvocellular subcortical pathways is at most 20 msec and may be as small as only 5 msec, or even less. This makes it difficult to attribute the latency in metacontrast to the latency differences between the magnocellular and parvocellular systems. It is therefore problematic to attribute reduced metacontrast masking to a deficit in the magnocellular system. PMID- 11766951 TI - Research in rehabilitation medicine. PMID- 11766952 TI - Neurological rehabilitation in the community. AB - There is increasing pressure on health services around the world to provide more resources and facilities in the community. This is partly as a counterbalance to the increasing cost of hospital services and partly a recognition of the importance of local health facilities. Rehabilitation has generally been a hospital-based specialty and there now needs to be a change of focus, or at least an additional focus, towards community rehabilitation. This review article summarizes some of the models of community rehabilitation and the evidence for their effectiveness. Although there is a reasonable body of evidence for both the acceptability and effectiveness of community rehabilitation there is a clear need for further research. PMID- 11766953 TI - The relationships between trunk function and the findings of transcranial magnetic stimulation among patients with stroke. AB - In this study, we investigated the relationship between the motor evoked potentials obtained from trunk muscles and the clinical function of trunk muscle. Twenty patients with unilateral hemispheric stroke and 11 healthy adults were examined. The responses of the bilateral external oblique muscles and the erector spinae muscles to the magnetic stimulation of multiple sites over both cortical hemispheres were recorded. Trunk muscle performance was assessed using the Trunk Control Test and Stroke Impairment Assessment Set. In the stroke group, stimulation of the affected hemisphere resulted in a motor evoked potential in only one patient, while the other 19 stroke patients produced no response to stimulation of the affected hemisphere. Stimulation of the unaffected hemisphere evoked bilateral responses in 19 patients. Further, stimulation of the unaffected hemisphere in the stroke group produced larger motor evoked potentials in the ipsilateral muscles than the motor evoked potentials recorded in the ipsilateral muscles of the control group. The clinical assessment scores of trunk function (i.e. Trunk Control Test and trunk items of Stroke Impairment Assessment Set) were correlated with the amplitudes of the motor evoked potentials of the ipsilateral external oblique muscle that were evoked by stimulation of the unaffected hemisphere. Our results suggest that the recovery of trunk function after stroke is associated with an increase in ipsilateral motor evoked potentials in the external oblique muscle upon stimulation of the unaffected hemisphere, suggesting a role for compensatory activation of uncrossed pathways in recovery of trunk function. PMID- 11766954 TI - A neural network for recognizing movement patterns during repetitive self-paced movements of the fingers in opposition to the thumb. AB - A data glove is a typical input device to control a virtual environment. At the same time it measures movements of wrist and fingers. The purposes of this investigation were to assess the ability of BrainMaker, a neural network, to recognize movement patterns during an opposition task that consisted of repetitive self-paced movements of the fingers in opposition to the thumb. The neural network contained 56 inputs, 3 hidden layers of 20 neurons, and one output. The 5th glove '95 (5DT), a commercial glove especially designed for virtual reality games, was used for finger motion capture. The training of the neural network was successful for recognizing the thumb, the index finger and the ring finger movements during the repetitive self-paced movements and neural network performed well during testing. PMID- 11766955 TI - Physical performance and health-related quality of life in men on a liver transplantation waiting list. AB - Twenty-six men on a liver transplant waiting list (12 had alcoholic cirrhosis, 8 suffered from posthepatitic cirrhosis, and 6 from cirrhosis of other etiologies) were eligible for this observation. Nineteen subjects underwent exercise testing to determine oxygen uptake at anaerobic threshold. In all patients dynamometry was performed to determine isokinetic muscle strength of knee extensor muscles, and handgrip. Quality of life was evaluated in all patients with the MOS SF-36 questionnaire. Child-Pugh A patients showed 54 +/- 8%, Child-Pugh B patients 36 +/- 2%, and Child-Pugh C patients 31 +/- 4% of VO2 max predicted at the anaerobic threshold (Kruskal-Wallis ANOVA, p < 0.05). Isokinetic muscle strength of the quadriceps femoris (left/right) was 149 +/- 20/134 +/- 14 Nm in Child-Pugh A, 108 +/- 16/114 +/- 19 Nm in Child-Pugh B, and 89 +/- 10/81 +/- 11 Nm in Child-Pugh C patients (Kruskal-Wallis ANOVA, p < 0.05). MOS-SF36 revealed a Child-Pugh class dependent reduced functional status (Kruskal-Wallis ANOVA, p < 0.05). No significant differences in target parameters were found when analysed according to the etiology of cirrhosis. Patients on the liver transplant waiting list do have a stage dependent reduction in physical health. These data are the basis for longitudinal studies measuring the effects of preoperative rehabilitation programs in these patients. PMID- 11766956 TI - The effect of a home physiotherapy program for persons with Parkinson's disease. AB - The purpose of this study was to evaluate the effect of a home physiotherapy program for persons with Parkinson's disease. Thirty-three patients took part in the study using a within-subject controlled design. Functional activities including walking and carrying out transfers were measured at home and in the hospital before and after a 6-week baseline period, after 6 weeks home physiotherapy and after 3 months follow-up. Spatiotemporal and plantar force variables of gait were determined with video and pododynography. Treatment provided by community physiotherapists consisted of teaching cueing and conscious movement control 3 times a week. The study revealed that patients had significantly higher scores on a functional activity scale after treatment in the home setting and to a lesser degree in hospital, a result, which was partly sustained at follow-up. However, duration of the transfer movements, spatiotemporal and plantar force variables were not significantly improved except for stride length. The results support application and development of the treatment concept and highlight that physiotherapy aimed at improving function in Parkinson's disease is best provided in the home situation. PMID- 11766957 TI - The use of outcome measures in physical medicine and rehabilitation within Europe. AB - The aim of the study was to survey the use of outcome measures in rehabilitation within Europe. It was envisaged that this would provide the basis for further studies on the cross-cultural validity of outcome measures. A postal questionnaire was distributed in November 1998 to 866 units providing rehabilitation. In total, 418 questionnaires were returned, corresponding to a response rate of 48%. These 418 centres treated an estimated 113,000 patients annually, undertaking 360,000 assessments. The survey focused on nine diagnostic groups: hip and knee replacement, low back pain, lower limb amputees, multiple sclerosis, neuromuscular disorders, rheumatoid arthritis, spinal cord lesions, stroke and traumatic brain injury. It identified a relatively small number of dominant outcome assessments for each diagnostic group and some variation in the preference for measures across regions. A large number of measures, however, are being used in one or a small number of locations and with relatively few patients. For rehabilitation of orthopaedic patients the majority of assessments undertaken are at the impairment level. For patients with neurological disorders the emphasis is mostly upon measures of disability. PMID- 11766958 TI - Reliability and responsiveness of three different pain assessments. AB - The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness. PMID- 11766959 TI - Lactobacillus sakei: recent developments and future prospects. AB - Lactobacillus sakei is one of the most important bacterial species involved in meat preservation and meat fermentation. In the last fifteen years, numerous studies have focused on this species due to its important role in food microbiology. The present paper reviews current knowledge of this emerging species in the fields of taxonomy, phylogeny and physiology, and metabolism. Recent developments in genetic tools and molecular genetics will also be emphasized to evaluate future prospects. PMID- 11766960 TI - A transcriptional luxAB reporter fusion responding to fluorene in Sphingomonas sp. LB126 and its initial characterisation for whole-cell bioreporter purposes. AB - The promoter probe mini-Tn5-luxAB-tet was used to create a luxAB transcriptional fusion responding to fluorene in the fluorene utilising bacterium Sphingomonas sp. LB126. The mutant strain, named L-132, was impaired in fluorene utilisation and strongly emitted light upon addition of fluorene to the growth medium. L-132 was initially characterised and examined for its potential use as a whole-cell biosensor in the perspective of quantifying fluorene in environmental samples. Activity of the reporter gene as a response to fluorene was detectable after 30 min and was optimal after 4 h. A linear response to fluorene concentrations within the water solubility range was achieved, with a detection limit of 200 microg per litre. Besides fluorene, L-132 weakly responded to the polycyclic aromatic hydrocarbons phenanthrene and dibenzothiophene, whereas strong responses were obtained with 9-fluorenone, 9-hydroxyfluorene, phthalic acid and protocatechuic acid. The latter four compounds are metabolites formed in course of fluorene degradation, which suggested that a fluorene metabolite rather than fluorene itself was the true inducer of the luxAB fusion in L-132. PMID- 11766961 TI - Fluorene degradation by Sphingomonas sp. LB126 proceeds through protocatechuic acid: a genetic analysis. AB - Sphingomonas sp. LB126 is able to utilize fluorene as sole source of carbon and energy. In the present study, a mutagenic vector was constructed and a "plasmid rescue" strategy was set up to isolate a 16.5-kb DNA fragment containing genes required for fluorene degradation. A 14.5-kb portion of the cloned DNA was sequenced revealing thirteen open reading frames. Two encoded hypothetical proteins (FldE and FldY) similar to transcriptional regulators and one (ORF360) located on an IS-like element (ISSsp126) encoded a putative transposase. Three other putative proteins (FldB, FldU and FldV) displayed strong similarity with enzymes of the protocatechuate 4,5-degradation pathway utilized by Sphingomonaspaucimobilis SYK-6 for the degradation of lignin breakdown products. The remaining hypothetical proteins displayed only limited similarity with enzyme sequences available from databases. Suicide plasmid-directed mutagenesis and genetic complementations showed that integrity of the protocatechuate catabolic pathway was an absolute requirement for fluorene degradation to proceed. These findings were further supported by the analysis of metabolites in bacterial culture supernatants obtained from appropriate mutants. The results presented here demonstrated the suitability of the genetic tool constructed and supplied the first genetic evidence for the participation of a protocatechuate 4,5 degradation pathway in a bacterial fluorene degradation pathway. PMID- 11766962 TI - Loss of lambda prophage recombinogenicity in UV-irradiated Escherichia coli: the role of host genes ruvA, ruvB, ruvC, and recG. AB - Earlier studies have revealed a radiation-induced process leading to the loss of lambda prophage recombinogenicity. The process takes place in UV-irradiated Escherichia coli cells, and renders the prophage incapable of site-specific recombination with the host chromosome, and of general recombination with an infecting homologous phage. It was found that the inhibition of prophage recombinogenicity depends on functional RecBCD enzyme of E. coli. In this work, the role of ruvABC and recG genes in the inhibitory process was assessed. The products of these genes are known to act at the last step of homologous recombination and recombinational DNA repair by catalyzing the resolution of recombination intermediates (the Holliday junctions). Irradiated prophage retained its ability to recombine in ruvA, ruvB, ruvC, and recG mutants. These results suggest that in addition to RecBCD enzyme, RuvABC and RecG proteins are also involved in the inhibition of prophage recombinogenicity. We infer that RuvABC and RecG act in this process before RecBCD, probably by processing the Holliday junctions formed upon replication arrest, and thereby providing double stranded DNA breaks as substrate for RecBCD-mediated recombinational repair of UV damaged bacterial chromosome. PMID- 11766963 TI - Streptomyces aureofaciens sporulation-specific sigma factor sigma(rpoZ) directs expression of a gene encoding protein similar to hydrolases involved in degradation of the lignin-related biphenyl compounds. AB - A previously established method for the identification of promoters recognized by a heterologous RNA polymerase holoenzyme containing a particular sigma factor was used to identify promoters dependent upon a sporulation specific sigma factor, sigma(RpoZ), of Streptomyces aureofaciens. Three new positive DNA fragments were identified, and these putative rpoZ-dependent promoters, P(ren24), P(ren57), and P(ren71), contained sequences similar to the consensus sequence of flagellar and chemotaxis promoters. However, only P(ren71) was active in S. aureofaciens. The promoter was induced at the time of aerial mycelium formation, and was inactive in an S. aureofaciens strain with an rpoZ-disrupted gene. The results suggest that the P(ren71) promoter is recognized by an RNA polymerase holoenzyme containing sigma(RpoZ) in S. aureofaciens. Sequence analysis of the region directed by P(ren71) revealed a gene, ren71, encoding a protein of 358 amino acids with an Mr 37,770. The deduced protein product showed end-to-end sequence similarity to the meta-cleavage compound hydrolase of Sphingomonas paucimobilis. PMID- 11766964 TI - Characterization of recombinant Bordetella pertussis adenylate cyclase toxins carrying passenger proteins. AB - Bordetella pertussis secretes a calmodulin-activated adenylate cyclase toxin, CyaA, that is able to deliver its N-terminal catalytic domain (400 amino acid residues) into the cytosol of eukaryotic target cells, directly through the cytoplasmic membrane. We have previously shown that CyaA can be used as a vehicle to deliver CD8+ T-cell epitopes, inserted within the catalytic domain of the toxin, into antigen-presenting cells and can trigger specific class I-restricted cytotoxic T-cell (CTL) responses in vivo. To explore the tolerance of CyaA to insertion of polypeptides of larger size, we constructed and characterized different recombinant CyaA toxins with protein inserts of 87 to 206 amino acids in length. Several of these recombinant CyaA toxins were found to be invasive. Furthermore, we showed that the unfolding of the passenger protein is a prerequisite for the translocation of the recombinant toxins into eukaryotic cells. Our results highlight the remarkable tolerance of the CyaA toxin and suggest that CyaA might be used to deliver proteins into eukaryotic cells. PMID- 11766965 TI - The manganese and iron superoxide dismutases protect Escherichia coli from heavy metal toxicity. AB - Superoxide dismutases (SODs) are vital components that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous SODs, a manganese- and an iron-containing enzyme (Mn-SOD and Fe SOD, respectively). In contrast, a single Mn-SOD is present in Bacillus subtilis. In E. coli, the absence of SODs was found to be associated with an increased sensitivity to cadmium, nickel and cobalt ions. Mutants lacking either sodA or sodB exhibited metal resistance to levels comparable to that of the wild-type strain. Although sod-deficient mutant cells were more resistant to zinc than their wild-type counterpart, no differences between the strains were observed in the presence of copper. In B. subtilis, the sodA mutation had no effect on cadmium and copper resistance. These results suggest that intracellular generation of superoxide by cadmium, nickel and cobalt is toxic in E. coli. They support the participation of sod genes in its protection against metal stress. PMID- 11766966 TI - Supplement 2000 (no. 44) to the Kauffmann-White scheme. AB - This supplement reports the characterization of 12 new Salmonella serovars recognized in 2000 by the WHO Collaborating Centre for Reference and Research on Salmonella: nine were assigned to S. enterica subsp. enterica, two to subspecies salamae, and one to subspecies diarizonae. PMID- 11766967 TI - Social inequality in the utilization of in- and outpatient treatment of non psychotic/non-organic disorders: a study with health insurance data. AB - BACKGROUND: This study deals with the utilization of in- and outpatient care due to non-psychotic/non-organic disorders (ICD-9 300-307: neuroses, personality disorders, sexual disturbances, alcohol and substance dependencies, drug abuse and functional disorders). Specifically, it examines whether social gradients to the detriment of individuals from lower social positions appear. This is dealt with both in terms of in- and outpatient treatment. Secondly, it examines whether the likelihood of being treated as an inpatient rather than an outpatient differs between occupational status positions. Finally, the study considers whether the hospital department a given patient is most likely to be assigned to differs between occupational status positions. METHOD: Analyses were performed with records from a statutory health insurance in West Germany. The database consists of 124,917 men and women between 20 and 60 years of age. We included only subjects with employment periods, as otherwise outpatient treatment could not be assessed completely. The data had been recorded between 1987 and 1996. In total, 9129 persons had one of the above mentioned diagnoses, 6115 of them received outpatient treatment and 3014 were inpatients only. RESULTS: The relative risk (RR) for outpatient diagnoses was RR=4.41 for the male unskilled/semi-skilled insured in comparison with men in the highest occupational position, the equivalent RR for women was 2.1. The respective results for inpatient treatment were RR=7.3 for men and RR=2.3 for women. In men, the relative risks were considerably reduced after cases with alcohol- and substance-related diagnoses had been excluded. For the assignment to in- and outpatient treatment, no consistent differences between individuals with different occupational positions emerged. Once diagnosed, higher-status individuals had the longest treatment periods as in- and outpatients. Only a small proportion of diagnosed subjects received medical care in psychiatric wards; this held especially for the group with higher occupational positions. CONCLUSIONS: Social inequalities in the treatment of psychogenic disorders emerged for outpatients as well as for inpatients. Inpatients tended to avoid treatment in psychiatric departments, and it can be concluded that individuals holding higher positions may be more successful in their attempts to avoid stigmatization. PMID- 11766968 TI - To be or not to be married--that is the question of quality of life in men with schizophrenia. AB - BACKGROUND: The association of gender and marital status with quality of life (QoL) was studied in a representative national sample of long-term schizophrenia patients. METHODS: The study sample consisted of 1,750 male and 1,506 female 15- to 64-year-old schizophrenia patients discharged from mental hospitals in 1986, 1990 and 1994 in Finland. Comprehensive data were collected from hospital and out patient case records and the psychiatric teams carried out a structured interview regarding the patients' socio-demographic background, living places, living situation, psycho-social state and functioning and life satisfaction three years after the index discharge. RESULTS: Female patients were older, more often married, had been ill for a longer time and had moved after discharge from hospital to live alone or with their spouse more often than men. Women and married patients had migrated more often than men and single patients, but single men had more often remained living in a remote rural area than others. The QoL of single men was poorer than others in almost all the areas in which it was measured: housing conditions, working, daily functioning, number of confidants and psycho-social state. Differences between single women and married men or women were much smaller. Women, independently of their marital status, were more satisfied with their life, had more close interpersonal relationships and had done useful work more often than men. CONCLUSIONS: Single male patients with schizophrenia seem to have dropped out of the development of society. They remain living in their birthplace and are more dependent than other patients. Single women migrate more consistently into urban areas, which may be favourable for their QoL. Married patients with schizophrenia, possibly partly helped by their spouse, can best follow changes in the society. Female gender also seems to have an independent association with life satisfaction and interpersonal aspects of the QoL. The results of this study strongly emphasise that the associations between gender, marital status and QoL to a great extent depend on the study sample and may also vary by study area. PMID- 11766969 TI - Changes in subjective quality of life among homeless adults who obtain housing: a prospective examination. AB - BACKGROUND: The aim of this present study is to examine whether overall subjective quality of life and specific domains of quality of life change among homeless adults after they become housed, and if so, what factors predict changes in satisfaction. METHODS: The data analysed here were collected through face-to face interviews with a sample of 485 homeless adults who were interviewed as often as bi-monthly over a 16-month period. Bivariate analyses examined initial differences between three groups: homeless people who did not exit from homelessness; those with an exit from homelessness to dependent housing; and those with an exit to independent housing. Bivariate analyses also examined differences in subjective quality of life before and after an exit from homelessness among the three groups. Multivariate analyses identified predictors of changes in quality of life before and after exit. RESULTS: This study has three main findings. First, homeless people who obtained independent housing had the largest positive and significant improvements in satisfaction with overall quality of life, and in satisfaction with housing, leisure and money. Second, becoming housed was not a predictor of changes in overall quality of life perceived by homeless people, nor in their satisfaction with leisure, clothing, food, and social life. Furthermore, a positive change in housing satisfaction was not associated with all types of exits from homelessness; only a move into independent housing predicted such a change, but a move into dependent housing did not. Finally, of all the covariates included as predictors at baseline, only two variables seemed to consistently predict changes in satisfaction; namely, self-assessed general health and self-assessed self-help skills. CONCLUSIONS: This study suggested that becoming independently housed may improve some aspects of quality of life for homeless people, but not others. The results suggest that homeless people prefer to be independently housed relative to remaining homeless or staying in a dependent housing situation, but that independent housing does not necessarily improve other aspects of their lives. PMID- 11766970 TI - Results of a screening survey for co-morbid substance misuse amongst patients in treatment for psychotic disorders: prevalence and service needs in an inner London borough. AB - BACKGROUND: There is great concern in the UK, and other countries, about the clinical management of psychosis and substance misuse co-morbidity. However, relatively little is known about the UK prevalence and management of co morbidity. METHOD: We implemented a screening survey of patients who were in treatment with an inner London adult mental health service and measured the prevalence of substance misuse amongst 851 psychotic patients. Caseworkers reported substance misuse and assessed clinical management arrangements. RESULTS: Current prevalence of substance misuse was 24.4% (95% CI: 21.3-27.1). Rates of co morbidity were higher in males (31% vs 16%, chi2 1df=26.0, P < 0.001) and patients over 51 (chi2 3df=50.1, P < 0.001). Adjusted odds of co-morbidity in patients under 51 were 0.19 (95% CI: 0.10-0.34) and 0.47 for females (95% CI: 0.32-0.69). Substance misuse interventions were provided to 20% of co-morbid patients--Only 5% were compliant. CONCLUSIONS: The findings suggest substance misuse may be highly prevalent amongst psychotic patients. Most co-morbid patients do not receive appropriate treatment. The development of evidence-based interventions should be a priority. PMID- 11766971 TI - A 22-year retrospective analysis of the changing frequency and patterns of religious symptoms among inpatients with psychotic illness in Egypt. AB - BACKGROUND: The aim of the present study was to assess the changes in frequency and pattern of religious symptomatology in a sample of psychiatric inpatients in Egypt suffering from some form of psychotic illness over the time span from 1975 to 1996. METHOD: A sample of 5275 files of psychotic inpatients at Behman psychiatric hospital in Cairo, Egypt, admitted between 1975 and 1996, were scrutinized for the presence or absence of "religious" symptoms. All the files with religious symptoms from this sample (n=632) and an additional 281 comparison files were analyzed. RESULTS: Significant fluctuations in the frequency of religious symptoms over the period of the study were noted. The frequency of religious symptoms peaked in the mid-1970s to early 1980s, and again in the early and mid-1990s, relative to other time periods. Further analyses of changes in the frequency of specific religious themes or symptoms revealed that religious behaviors (i. e., increased reading of religious texts, preaching, and other types of overt religious expression), in particular, showed significant and consistent patterns of change. CONCLUSIONS: These findings were interpreted in light of the fluctuating emphasis on religion and religious affiliation in everyday life in Egypt during the period of the study. While the overall frequency of religious delusional themes in Egypt is sensitive to societal changes across time, the specific content of these delusions remains stable. On the other hand, the relative salience of behavioral modes of pathological religious expression is highly influenced by changing patterns of religious emphasis in Egyptian society. PMID- 11766972 TI - From long-stay psychiatric hospital to Community Care Unit: evaluation at 1 year. AB - BACKGROUND: In the context of deinstitutionalization of psychiatric services, Community Care Units (CCUs) were developed to provide accommodation, clinical care and rehabilitation for patients discharged from the long-stay open wards of a large psychiatric hospital that was in the process of closing. CCUs are 20-bed units built in suburban locations and staffed on a 24-h basis by multidisciplinary clinical teams. METHOD: An initial group of 125 hospital patients was assessed at 1 month pre-move, 1 month post-move, and again at 1 year, on range of measures covering clinical status, personal functioning, quality of life, residential preferences, aggressive behaviour, and social networks. Staff attitudes, relative and carer perceptions and preferences, and residential environments were also assessed. RESULTS: Most of the transferred patients were still resident in their CCU at 1 year. The clearest result was that patients showed improved quality of life in relation to their living environment. Comparison of the hospital and CCU environments showed that the latter were significantly less restrictive and regimented. Most relatives and carers also preferred the CCU. On average, symptom and disability levels were little changed at 1 year. CONCLUSIONS: Our results suggest that the CCU is an appropriate form of service delivery for most long-stay hospital inpatients, but that both more and less supervised settings are also required. While symptoms and disability were little changed at 1 year, it is possible that further follow-up may detect delayed or slow changes. Given the widespread replacement of psychiatric hospitals with community-based services, the future role of the CCU needs to be reviewed. PMID- 11766973 TI - Collective approaches for the control of depression in England. AB - OBJECTIVE: This paper addresses the prevention and treatment of depression in the general population. It argues that the public health burden of depression cannot be effectively tackled solely at the level of the treatment of individuals; in addition, coherent strategies by national governments are required. It summarises some of the public health interventions that were undertaken in England by the government to reduce the risk factors associated with depression in increase detection and treatment and to destigmatise this disorder. Lessons learned from this experience are described. METHODS: To assess the scope for collective public interventions, a national psychiatric morbidity study was commissioned. The Government set targets for reducing psychiatric morbidity and suicide. Research related to depression was commissioned. A public information strategy was launched to increase understanding and reduce stigma, including a five year 'Defeat Depression' Campaign. Particular attention was paid to updating General Practitioners in the recognition, detection and management of depression. Government departments worked with employers and trade union organisations to attempt to reduce work-induced stress. Universal and selective prevention measures aimed to reduce factors associated with depression, such as unemployment. Measures to reduce suicide include education of health and social care professionals, supporting high-risk groups and restricting access to means of suicide. The impact of these strategies is difficult to assess and will not be apparent until the national psychiatric morbidity study is repeated in 2001. The overall suicide rate fell by 11.7% in five years. PMID- 11766974 TI - Self-reported life-weariness, death-wishes, suicidal ideation, suicidal plans and suicide attempts in general population surveys in the north of Sweden 1986 and 1996. AB - BACKGROUND: The aims of present study were to assess the prevalence of suicidal expression in the general population, to compare prevalences over time, to identify risk groups and to examine the evidence regarding the proposition that there is a continuous sequence of suicidal expressions with an underlying gradient of severity. METHOD: Two postal questionnaire studies were conducted, in 1986 and in 1996, involving representative samples of about 700 and 1000 persons respectively, in the age range 18-65 years. Response rates of 76% and 64%, respectively, were obtained. RESULTS: A higher proportion (34%) reported some degree of suicidal expression during the past year in the 1996 survey, compared to 1986 (23%). This was mainly attributed to higher reporting of life-weariness and death-wishes, since there was a simultaneous lower reporting of suicidal ideation (12.5% vs 8.6%). The total lifetime incidence of suicidal expression was identical (52%) in both studies. Respective proportions of 0.6% and 0.2% reported that they had made a suicide attempt during the last year, and 2.6% and 2.7%, respectively, during their lifetime. Higher prevalences of combined suicidal expression during the previous year were reported by women, younger persons, those living alone and women living in urban areas. Concerning suicidal ideation during last year, no gender differences were found. For a total of 21% of those reporting some degree of suicidal expressions during the past year, no simple cumulative relationship between the different types of suicidal expression was found. CONCLUSIONS: It is possible to use a postal questionnaire approach for studies on suicidal expression in the general population, and the study indicates that such suicidal expression is fairly prevalent. The pronounced gender differences concerning most types of suicidal behaviours and expression are not valid for suicidal ideation, which is important to consider in a preventional context. PMID- 11766975 TI - Social class and suicidal behaviour: the associations between social class and the characteristics of deliberate self-harm patients and the treatment they are offered. AB - BACKGROUND: Rates of deliberate self-harm (DSH) in the United Kingdom are much higher in lower than upper social class groups. Previous investigations have shown differences in socio-demographic and clinical characteristics of male patients according to social class. In two studies of DSH patients in Edinburgh the extent of provision of psychiatric aftercare was inversely related to social class. These findings have not been investigated in other areas. METHOD: Data collected through the Oxford Monitoring System for Attempted Suicide were used to examine the association between social class and socio-demographic and clinical characteristics in male and female DSH patients who presented to the general hospital in Oxford between mid-1988 and 1996 and to determine whether the previously reported social class differences in provision of psychiatric aftercare were replicated. RESULTS: Data on social class were available for 2,828 DSH patients (1,290 males, 1,538 females). In both genders, lower social class group tended to be associated with younger age. In males, the main social class differences were found in under-35-year-olds, in whom lower social class was related to criminal record, violence to others and drug misuse. In females, psychiatric disorders were diagnosed more frequently in the higher social class groups, but only in the under-35 age group. In neither gender was there a significant association between social class and the frequency of offer of psychiatric aftercare following DSH. CONCLUSIONS: There are considerable variations in socio-demographic and clinical characteristics of both male and female DSH patients in different social classes, especially in younger patients. The reason for the absence of a marked social class gradient in psychiatric aftercare found in this study in contrast to the results from previous investigations may be related to differences in styles of service. PMID- 11766976 TI - Maintaining contact with people with severe mental illness: 5-year follow-up of assertive outreach. AB - BACKGROUND: Assertive outreach is a central strand of Government mental health policy in England. Are different long-term models of mental health care which include assertive outreach associated with different service user outcomes and cost? METHOD: We conducted a multi-site 5-year follow-up study of people with severe mental illness. From 0 to 18 months all three sites had Intensive Case Management (ICM) teams practising assertive outreach. From 18 to 60 months one team sustained ICM, one team merged and another was disbanded. All 131 original ICM team clients were the study participants. Outcome was measured in terms of sustained engagement with statutory mental health services, psychiatric symptoms, social functioning, resource use and cost. RESULTS: All 120 live participants were traced. Only four people had no service contact; when contacted by a researcher they appeared to be coping well. No incidents of serious violence were discovered. No differences existed between teams in the mean total symptom or total social functioning change scores at follow-up, after controlling for baseline differences. No differences existed in mean cost between teams during the first 18 months. Mean (standard deviation) annualised costs varied considerably in the 18-60 month period: sustained team Pound Sterling13,734 (10,820); integrated team Pound Sterling11,037 (13,603); disbanded team Pound Sterling5,742 (7,007) (F=4.4, 105 df, p=0.015). CONCLUSION: Continued specialist assertive outreach service models have higher costs than non-specialist services for no apparent benefit. In the long term new assertive outreach services should have procedures in place to transfer people to lower intensity and lower cost care. PMID- 11766977 TI - Drug and alcohol problems amongst individuals with severe mental health problems in an inner city area of the UK. AB - BACKGROUND: The extent and impact of drug and alcohol use among those with severe mental health problems has been well documented in the US. However, little is known of the nature of this problem in the UK, particularly in community treatment settings. This paper outlines findings from a large-scale survey conducted across community-based Mental Health and Substance Misuse services, which aimed to ascertain the prevalence of drug and alcohol problems among those with severe mental health problems. METHOD: An assessment instrument was completed by keyworkers for each of their clients, which included mental health diagnosis and an adapted version of the Clinician Rating Scales for Alcohol and Drug Use. RESULTS: From a sample of 3079 clients across services, 1369 clients were identified with a severe mental illness diagnosis. According to their key workers, 24% of these clients (324/1369) had used alcohol and/or drugs problematically during the past year. These individuals were most likely to have a diagnosis within the schizophrenia cluster, were mainly white males in their mid-30s, and tended to be located within Mental Health services in Assertive Outreach teams and to be higher utilisers of crises/emergency services. CONCLUSIONS: It can be concluded that similar to other studies in inner city areas of the UK, problem substance use is common amongst those with severe mental health problems within Northern Birmingham. PMID- 11766978 TI - Relatives of patients with severe psychotic illness: factors that influence appraisal of caregiving and psychological distress. AB - BACKGROUND: Research shows considerable variability in the effect on relatives of patients' mental illness but the determinants of relatives' experience remain unclear. We investigated the influence of demographic, social and clinical characteristics on relatives' experience when conceptualised using a stress appraisal-coping paradigm. METHODS: Our sample was drawn from relatives of patients recruited to the UK700 case management study (n = 154). Demographic, social and clinical data were collected from patients, and relatives completed the Experience of Caregiving Inventory and the General Health Questionnaire. We predicted that patients' symptomatology in particular would influence relatives' experience, and that relatives who appraised caregiving more negatively and less positively would experience greater psychological distress. RESULTS: Linear regression analyses revealed that relatives' appraisal was not predicted by patients' symptomatology. Instead, relatives appraised caregiving more negatively if the patient was unemployed or younger, and less positively if the patient had been ill for longer or had poorer social functioning. Little of the variance in appraisal was explained by these variables, however. Consistent with the stress coping model, relatives' negative appraisal was a strong predictor of psychological distress and accounted for a substantial proportion of its variance. Positive appraisal did not predict psychological distress, however. None of the demographic, social or clinical characteristics tested had any significant effect on relatives' psychological distress once appraisal was adjusted for. There was an unexpected positive correlation between the two appraisal scales, with relatives who appraised caregiving more negatively also appraising it more positively. CONCLUSIONS: Our results support a stress-coping model of caregiving but further research is required to determine more influential predictors of relatives' appraisal. Our findings indicate that interventions aimed at patients' social functioning and relatives' negative appraisal of caregiving may assist in reducing relatives' psychological distress. PMID- 11766979 TI - Abnormal eating attitudes and behaviours and perceived parental control: a study of white British and British-Asian school girls. AB - BACKGROUND: Previous studies have found significantly higher scores on the Eating Attitudes Test (EAT-26) which measures eating disorders among second-generation British-Asian schoolgirls in comparison to their White counterparts. Further, high EAT-26 scores (an indication of unhealthy eating attitudes and behaviours) are positively associated with parental overprotection scores on the Parental Bonding Instrument (PBI). This study aimed to replicate and extend previous findings, comparing British-Asian schoolgirls to White schoolgirls and consider 'intra-Asian' differences on the same measures, including factor scores. METHODS: Participants completed three questionnaires: EAT-26, PBI and BSS (Body Satisfaction Scale). There were 168 participants: 46 White, 40 Indian, 44 Pakistani and 38 Bengali. RESULTS: Previous findings were supported; the Asian scores were significantly higher than the White scores on the EAT-26 and PBI, but not the BSS. The Bengali sample had significantly higher EAT-26 total and 'oral control' scores than the other groups. There were no intra-Asian differences for the overprotection scores. PBI scores were not associated with EAT-26 scores. The BSS score was the only significant predictor of EAT scores, when entered into a regression along with PBI scores and the body mass index. CONCLUSION: Results demonstrated sociocultural factors in the development of eating disorders. The results suggest that there are important psychological differences between second generation migrants from different countries on the Indian subcontinent. In line with previous studies, significant differences were found between the four ethnic groups, parenting styles, but these did not relate to actual eating disorders. PMID- 11766980 TI - Sub-Angstrom high-resolution transmission electron microscopy at 300 keV. AB - Sub-Angstrom transmission electron microscopy has been achieved at the National Center for Electron Microscopy (NCEM) by a one-Angstrom microscope (OAM) project using software and enhanced hardware developed within a Brite-Euram project (Ultramicroscopy 64 (1996) 1). The NCEM OAM provides materials scientists with transmission electron microscopy at a resolution better than 1 A by using extensive image reconstruction to exploit the significantly higher information limit of an FEG-TEM over its Scherzer resolution limit. Reconstruction methods chosen used off-axis holograms and focal series of underfocused images. Measured values of coherence parameters predict an information limit of 0.78 A. Images from a [1 1 0] diamond test specimen show that sub-Angstrom resolution of 0.89 A has been achieved with the OAM using focal series reconstruction. PMID- 11766981 TI - Imaging columns of the light elements carbon, nitrogen and oxygen with sub Angstrom resolution. AB - It is reported that lattice imaging with a 300 kV field emission microscope in combination with numerical reconstruction procedures can be used to reach an interpretable resolution of about 80 pm for the first time. A retrieval of the electron exit wave from focal series allows for the resolution of single atomic columns of the light elements carbon, nitrogen, and oxygen at a projected nearest neighbor spacing down to 85 pm. Lens aberrations are corrected on-line during the experiment and by hardware such that resulting image distortions are below 80 pm. Consequently, the imaging can be aberration-free to this extent. The resolution enhancement results from increased electrical and mechanical stability of the instrument coupled with a low spherical aberration coefficient of 0.595 + 0.005 mm. PMID- 11766982 TI - Early detection of cytotoxic events between hepatic natural killer cells and colon carcinoma cells as probed with the atomic force microscope. AB - The atomic force microscope (AFM) is a powerful tool to investigate surface and submembranous structures of living cells under physiological conditions at high resolution. These properties enabled us to study the interaction between live hepatic natural killer (NK) cells, also called pit cells, and colon carcinoma cells in vitro by AFM. In addition, the staining for filamentous actin and DNA was performed and served as a reference, because actin and nuclear observations at the light microscopic level during the cytotoxic interaction between these two cell types have been presented earlier. In this study, we collected evidence that conjugation of hepatic NK cells with CC531s colon carcinoma cells results in a decreased binding of CC531s cells to the substratum as probed with the AFM in contact mode as early as 10 min after cell contact (n = 11). To avoid the lateral forces and smearing artefacts of contact mode AFM, non-contact imaging was performed on hepatic NK/CC531s cell conjugates, resulting in identical observations (n = 3). In contrast, the first cytotoxic signs, as determined with the nuclear staining dye Hoechst 33342, could be observed 3 h after the start of the co-culture. This study illustrates that the AFM can be used to probe early cytotoxic effects of effector to target cell contact in nearby physiological conditions. Other routine cytotoxicity tests detect the first cytotoxic effects after 1.5-3 h co-incubation at the earliest. PMID- 11766983 TI - Does a monochromator improve the precision in quantitative HRTEM? AB - This paper addresses the question as to what extent the incorporation of a monochromator in an electron microscope can enhance the performance of high resolution transmission electron microscopy (HRTEM). The monochromator will reduce the chromatic aberration, and hence the information limit, at the expense of beam current, leading to a decrease in signal intensity and a corresponding decrease in signal-to-noise ratio (SNR). Both aspects, information limit and SNR, have been included in a quantitative evaluation based on the statistical precision with which the position of an atom column can be estimated. It is shown that the effect of a monochromator on the attainable precision depends on the microscope and monochromator parameters, as well as on the characteristics of the object. PMID- 11766984 TI - Potential-induced resonant tunneling through a redox metalloprotein investigated by electrochemical scanning probe microscopy. AB - The redox metalloprotein azurin self-chemisorbed onto Au(1 1 1) substrates has been investigated by electrochemically controlled scanning tunneling (STM) and scanning force/lateral force microscopy (SFM/LFM) and cyclic voltammetry (CV) in aqueous solution. The combined use of STM and SFM/LFM under electrochemical control in the negative side of the azurin redox midpoint (+116 mV vs. SCE) has delivered unique information on the nature of the STM images. While in STM the bright spots, believed to be associated with azurin molecules, are visible only for potential values higher than -125 mV, the concurrent electrochemical SFM results show adsorbed proteins over the whole potential range investigated (from 225 to +75 mV). Stepping the potential back and forth (between -25 and -125 mV) in STM imaging, it has been possible to make bright spots appearing and disappearing repeatedly, indicating that STM image formation arises possibly through resonant tunneling via the redox levels of azurin. These results represent the first clear evidence of potential-dependent tunneling in proteins adsorbed onto a conductive substrate. PMID- 11766985 TI - LACBED measurement of the chemical composition of a thin In(x)Ga(1-x)As layer buried in a GaAs matrix. AB - Large angle convergent beam electron diffraction (LACBED) observations are used to determine the x indium content of a thin In(x)Ga(1-x)As quantum well buried in a GaAs matrix. The method consists in a quantitative analysis of the Bragg line intensities lying in the central disc of any LACBED pattern. This analysis makes it possible to determine the displacement vector R introduced, between the two parts of the GaAs matrix, by the deformation of the quantum well and consequently to determine the x indium content. This indium content is found to be consistent with the value expected from the molecular beam epitaxy growth conditions. PMID- 11766986 TI - Heterodimeric amino acid transporters: molecular biology and pathological and pharmacological relevance. AB - In the last decade, a lot of amino acid transporters were identified by molecular cloning and assigned to the classically characterized amino acid transport systems. Among them, ones which belong to the heterodimeric amino acid transporter family are unique because of their broad substrate selectivity and their pathological implications as well as their structural features. The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters as well as 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning type II membrane glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT (related to b(0,+)-amino acid transporter). Six members are associated with 4F2hc and one is linked to rBAT. The neutral amino acid transporter of this family seems to rely on the hydrophobic interactions for their substrate recognition which can explain their broad substrate selectivity. Because of this characteristic, they can permeate amino-acid-related drugs and contribute to the pharmacokinetics of these drugs. A neutral amino acid transporter LAT1 (L-type amino acid transporter 1) has actually been shown to be present at the blood-brain-barrier. Because the members of the heterodimeric amino acid transporter family exhibit variety of substrate selectivity, it is proposed that this family members have been diverged from the prototype neutral amino acid transporter such as LAT1 by acquiring the mechanisms for the recognition of electric charges on the substrate amino acid side chains. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters BAT1/b(0,+) AT (b(0,+) type amino acid transporter 1/b(0,+)-type amino acid transporter) and y+ LAT1 (y+ L-type amino acid transporter 1) result in the amino aciduria with sever clinical symptoms such as cystinuria and lysinuric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x- C-type transporter) functions to protect cells against oxidative stress, while its over function may be damaging neurons leading to the exacerbation of brain damage after, brain ischemia. Therefore, these transporters would be candidates for therapeutic targets based on new strategies. Through the interaction with the associating proteins, the transporters of this family would be endowed with more possibility to be regulated via intracellular and extracellular signalling pathways, which is critical to tune the transporter functions to meet the metabolic requirements of cells. PMID- 11766987 TI - Contribution of specific transport systems to anthracycline transport in tumor and normal cells. AB - Anthracycline antibiotics are very effective neoplastic agents widely used clinically. However, because of their many adverse effects (e.g. cardiotoxicity, leukopenia and alopecia), their clinical use has been limited. In order to minimize their adverse effects in clinical cancer chemotherapy, anthracyclines must be selectively transported into tumor cells. If there are differences in transport characteristics between tumor and normal cells, it should be possible to establish a strategy for selectively delivering anthracyclines to tumor cells on the basis of the differences. In human cultured leukemia HL60 cells, as tumor cells, and human fresh mononuclear cells, as normal cells, doxorubicin, pirarubicin, daunorubicin and idarubicin were incorporated via a common carrier mediated system, but the carriers were different in the two cell types. In HL60 cells, it was indicated that a nucleoside transport system contributed, at least in part, to the transport of doxorubicin and pirarubicin, but not daunorubicin and idarubicin, and its contribution to pirarubicin transport was found in other tumor cells, i.e. mouse ovarian sarcoma M5076 and Ehrlich ascites carcinoma cells. On the other hand, in mononuclear cells, there was no involvement of a nucleoside transport system for the four anthracyclines examined. Therefore, we thought that with the modification of an anthracycline molecule as a substrate for the nucleoside transport system, the anthracycline could be delivered selectively to tumor cells. PMID- 11766988 TI - The MRP family and anticancer drug metabolism. AB - Acquirement of drug resistance by tumor cells is a major chemotherapeutic problem. It is well known that typical multidrug resistance is caused by P glycoprotein and multidrug resistance related protein (MRP1) which belong to the ATP binding cassette (ABC) transporter family. Ishikawa proposed that the ATP dependent glutathione-S-conjugate export pump (GS-X pump) and phase III detoxification system are essential to drug metabolism, and this constituted a new concept in drug metabolism and the detoxification of xenobiotics. The GS-X pump has been revealed to belong to the ABC transporter family and suggested to the contribution to anticancer drug resistance. The GS-X pump actively effluxes the glutathione S-platinum (GS-Pt) complex. We cloned novel ABC transporter cDNA from the PC-14/CDDP cell line, and the cloned cDNA was designated as a short-type MRP homologue, SMRP. Further investigation suggested that SMRP is a splicing variant of MRP5. The MRP5 mRNA levels in tumors from lung cancer patients treated with platinum regimen were significantly higher than in tumors from patients treated with non-platinum regimens, and the MRP5 expression levels were correlate with the GCS expression levels that is the rate-limiting step enzyme in glutathione biosynthesis. These results suggested that MRP5 take part in the function of GS-X pump. Recently many transporter molecules belong to the ABC transporter family such as MRP family have been identified, and appear to express in various human tissues. It can be presumed that their molecules are affected by the disposition and metabolism of drugs, but their substrates are still unclear. If the substrate specificity is revealed in the future, it is expected that the anticancer agents transporter, moreover anti cancer drug resistance mechanisms, can be clarified. This review is cited in the cisplatin resistance and the GS-X pump, and finally describes an overview of the MRPs substrates recently clarified, mainly about anticancer drugs. PMID- 11766989 TI - Effect of methylxanthine derivatives on doxorubicin transport and antitumor activity. AB - Biochemical modulation, which is more effective with the use of antitumor agents, has recently played very important role in cancer chemotherapy. In this review, it was reported that some of the methylxanthine derivatives, e.g. caffeine, were useful for modulator and attempted to defined the relation between the effect of methylxanthine derivatives on the doxorubicin transport and antitumor activity. Caffeine and theobromine inhibited the doxorubicin efflux from tumor cells, increased the doxorubicin concentration in a tumor, and enhanced the antitumor effect of doxorubicin. However, the caffeine metabolites, which had no effect on the doxorubicin efflux, did not increase antitumor activity. Moreover, caffeine and theobromine did not enhance the side toxicity of doxorubicin on the lipid peroxide level, DNA biosynthesis and the doxorubicin concentrations in normal tissues. Moreover, we investigated the effect of the combination of doxorubicin with caffeine or theobromine on the change in cyclic adenosine 3',5' monophosphate (cyclic AMP) in tissues in vivo, and the effect of cyclic AMP on doxorubicin efflux in vitro, and measured the distribution of caffeine and theobromine in normal and tumor tissues. In Ehrlich ascites carcinoma bearing mice, the level of cyclic AMP in a tumor was decreased by doxorubicin. With the combination of caffeine or theobromine and doxorubicin, the cyclic AMP level recovered to the control level. This tendency was not seen in normal tissues (heart and liver). Moreover, the doxorubicin efflux from the Ehrlich cells was inhibited on the addition of cyclic AMP in vitro. And the caffeine concentration in the tumors was the same as that in the heart, and was increased in combination with doxorubicin compared with that in the caffeine-only group during the 4 hr after caffeine treatment. Furthermore, the doxorubicin efflux was promoted by the supply of energy (addition of glucose), influx was decreased relatively, doxorubicin efflux needs the existence of glucose and the inhibition of energy related drug export pump by caffeine induced inhibition of doxorubicin efflux. The treatment of doxorubicin nor caffeine, and any treatment schedule did not change the amount and appearance of GLUT 1 as glucose transporter on Ehrlich ascites carcinoma cell. For the mentioned above, we thought as concerns the increase of antitumor activity of doxorubicin by caffeine which is xanthine derivatives as follows. Caffeine distributes, high level in tumor, keeps the cyclic AMP level, and effects glucose transport or doxorubicin transport depend on energy and inhibits doxorubicin efflux. And then DNA synthesis was increased with the maintenance the concentration of doxorubicin in tumor. These action did not show in normal tissues, caffeine did not influence the side toxicity of doxorubicin. These results suggested that caffeine which is one of xanthine derivatives will be useful for biochemical modulator. PMID- 11766990 TI - Interactions of liposomes with cells in vitro and in vivo: opsonins and receptors. AB - A number of studies have appeared recently on the underlying mechanisms of liposome-cell interactions under in vitro conditions, in which isolated cell populations or cell lines were used. However, our knowledge of how liposomes interact with cells and the parameters that influence this in vivo is limited. We will summarize and discuss the relevant studies on this matter in this article. In addition, researchers in this field have long been aware of the interaction of liposomes with blood (or serum/plasma) proteins in vivo and their potential role in the process of the clearance of liposomes from the circulation. Some of the 'opsonizing' proteins, such as complement components, immunoglobulins, which enhance the interactions of liposomes with 'phagocytic cells' have been identified. However, the issue of which types of opsonins determine the fate of liposomes in vivo and how liposomal physicochemical properties such as size, charge and fluidity play an important role in the process of liposome clearance is not clear. Our own observations of one of opsonins, complement component are reviewed herein. As opposed to the fate of conventional liposomes, we briefly touch on the interaction of surface-modified liposomes, which are designed to avoid interactions with blood proteins and/or cells (sterically stabilized liposomes, long-circulating liposomes) and to actively target specific cells or tissues (targeted liposomes: immunoliposomes). Blood proteins such as opsonins are not usually thought to play an important role in the clearance of such liposomes. PMID- 11766991 TI - Application of an in vivo brain microdialysis technique to studies of drug transport across the blood-brain barrier. AB - There is a wide range of methods available for studying the transport of drugs across the blood-brain barrier (BBB) which is equipped with several systems to transport drugs as well as endogenous nutrients and waste products. The in vivo brain microdialysis technique, which allows direct sampling of the brain interstitial fluid (ISF), is a powerful means of characterizing influx and efflux transport across the BBB. In this paper, we review our results from the successful application of this technique to BBB drug transport studies. The drugs investigated include novel and CNS-active peptides, some agents that are actively removed from the brain ISF across the BBB, and a brain-directed prodrug. PMID- 11766992 TI - Fractalkine induces chemotaxis and actin polymerization in human dendritic cells. AB - OBJECTIVE AND DESIGN: Dendritic cells (DCs) are considered as the principle initiators of immune responses by virtue of their ability to migrate into target sites, process antigens and activate naive T cells. Here, the chemotactic activity and intracellular signaling of fractalkine was analyzed and compared to well known chemotaxins. METHODS: The mRNA-expression of G protein-coupled CX3CR1 was analyzed by RT-PCR. Chemotaxis was measured in 48-well Boyden chambers and actin polymerization by flow cytometry. RESULTS: The mRNA-expression of CX3CR1 in immature and mature DCs was revealed. Fractalkine elicited actin polymerization and chemotaxis in a dose-dependent manner in DCs independent of their state of maturation. CONCLUSIONS: These results show that immature and mature DCs express mRNA for the CX3CRI and that fractalkine induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs, contrasting with the action of other chemokines such as RANTES or MIP-3beta which act only on distinct maturation states of DCs. PMID- 11766993 TI - Modulation of leukocyte-endothelium interaction by nitric oxide synthase inhibitors: effects on leukocyte adhesion in endotoxin-induced uveitis. AB - OBJECTIVE AND DESIGN: To examine the effects of the nitric oxide synthase (NOS) inhibitors aminoguanidine (AG) and L-NAME on leukocyte adhesion in endotoxin induced uveitis (EIU). MATERIAL: Uveitis was induced in Lewis rats (n = 124) by LPS injection (Salmonella typhimurium). TREATMENT: Rats either (1) did not receive any LPS or other treatments (controls), received (2) only subcutaneous saline injections with LPS administration, (3) a single s.c. dose of AG (100 mg/kg body weight) at the time of LPS administration, (4) a single s.c. injection of AG 8 h after LPS injection, (5) s.c. injections of AG at the time of LPS administration and 8 h after LPS injection or (6) received a single dose of L NAME (75 mg/kg body weight) at the time of LPS administration. METHODS: Intravital microscopy (IVM) of iris vessels was performed at 2, 4, 8, 16, 24 and 48 h after endotoxin injection. Aqueous humor analysis for protein concentration and cell count was performed after IVM. RESULTS: At 2 h after the induction of uveitis, significantly more rolling leukocytes were detected in the AG and L-NAME treated group than in untreated EIU (4.8 +/- 0.31 and 9.83 +/- 0.64 vs. 2.85 +/- 0.37%, mean +/- SEM, p < 0.01). However, at 16 h the percentage of rolling leukocytes was significantly reduced in all groups which had received AG (LPS: 8.08 +/- 0.37%; LPS/AG 0 h: 3.78 +/- 0.25%; LPS/AG 8 h: 5.34 +/- 0.3%; LPS/AG 0+8h: 3.86 +/- 0.31%). L-NAME enhanced leukocyte rolling even at 24 h after LPS (12.38 +/- 0.64%). Early treatment of EIU with AG significantly reduced the number of sticking leukocytes at 4, 8 and 24 h (306 +/- 13 vs. 571 +/- 41, 228 +/ 12 vs. 345 +/- 19 and 240 +/- 14 vs. 469 +/- 23 cells/mm2, respectively). L-NAME inhibited LPS-induced sticking of leukocytes at all observed time points and this effect was most pronounced at 24 h (147 +/- 10 vs. 469 +/- 23 cells/mm2). CONCLUSIONS: In EIU, administration of AG or L-NAME causes enhanced leukocyte rolling in the early inflammatory response. However, firm adhesion of leukocytes to the vascular endothelium decreases and this effect prevails, ameliorating leukocyte infiltration. PMID- 11766994 TI - Inhibition of P-selectin specific cell adhesion by a low molecular weight, non carbohydrate compound, KF38789. AB - OBJECTIVE AND DESIGN: P-selectin is a cell adhesion molecule of the selectin family. This study evaluated the effects of novel, low molecular weight P selectin inhibitors in a cell adhesion assay and a murine model of peritonitis. MATERIALS: U937 or HL60 was used for cell adhesion assay. Human polymorphonuclear cells were studied for the production of superoxide. BALB/c mice were used for the in vivo study. TREATMENT: The thioglycollate (TG)-induced accumulation of leukocytes in mice was measured 6 h after the treatment. KF38789 or antibody (1 mg/kg) was injected intravenously prior to TG injection and at 3 h following initial injection. RESULTS: Low molecular weight, non-carbohydrate inhibitors against P-selectin- mediated cell adhesion were tested. One of the most potent inhibitors, KF38789, inhibited the binding of U937 cells to immobilized P selectin immunoglobulin G chimeric protein (P-selectin-Ig) with an IC50 value of 1.97 microM. Cell adhesion to both E-selectin-Ig and L-selectin-Ig were not affected even by 100 microM of KF38789. Moreover, KF38789 inhibited P-selectin induced superoxide production from human polymorphonuclear cells. Intravenously injected KF38789 significantly inhibited the TG-induced accumulation of leukocytes in the mouse peritoneal cavity (p<0.01). CONCLUSION: A novel low molecular weight compound, KF38789, specifically inhibited P-selectin-dependent cell adhesion and the leukocyte recruitment in mouse peritonitis. PMID- 11766996 TI - Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase. AB - OBJECTIVE AND DESIGN: Oxygen- and nitrogen-derived free radicals and oxidants play an important role in the pathogenesis of various forms of inflammation. Recent work emphasizes the importance of oxidant-induced DNA strand breakage and activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in the pathogenesis of various inflammatory diseases. We have recently demonstrated the efficacy of PJ34, a novel, potent phenanthridinone derivative PARP inhibitor, in rodent models of diabetic vascular dysfunction and stroke. Here we tested the efficacy of PARP inhibition in various models of local inflammation in rodents. MATERIALS AND METHODS: PJ34 (at doses of 0.03-30 mg/kg) was tested in rats and mice subjected to standard models of inflammation, with relevant parameters of inflammation measured using standard methods. RESULTS: PJ34 treatment (s.c, i.p. and i.v.) dose-dependently suppressed neutrophil infiltration and nitric oxide (but not KC and IL-1beta) production in peritonitis. In a model of systemic endotoxemia, PJ34 pretreatment significantly reduced plasma levels of TNF-alpha, IL-1beta and nitrite/nitrate (breakdown products of nitric oxide) production. PJ34 treatment (oral gavage) induced a significant suppression of the inflammatory response in dextran sulfate colitis, multiple low dose streptozotocin diabetes and cyclophosphamide-accelerated autoimmune diabetes in the non-obese diabetic mice, and reduced the degree of mononuclear cell infiltration into the iris in an endotoxin-induced uveitis model. Delaying the start of PJ34 administration in the colitis model conferred significant protective effects, while in the arthritis model the post-treatment paradigm lacked protective effects. CONCLUSIONS: PJ34 provides significant, dose dependent, anti-inflammatory effects in a variety of local inflammation models. Some of its actions are maintained in the post-treatment regimen and/or after discontinuation of treatment. We conclude that PARP inhibition offers a powerful means for reducing the severity of various forms of local inflammatory responses. PMID- 11766995 TI - IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2. AB - Fungus-induced asthmatic disease is characterized by persistent airway hyperreactivity and remodeling. OBJECTIVE AND DESIGN: To determine the role of IL 18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatus-induced asthma. METHODS: A. fumigatus-sensitized mice were depleted of IL-18 using a polyclonal anti-IL-18 antibody for 3 days after a conidia challenge. RESULTS: Airway hyperresponsiveness and eosinophil numbers were significantly elevated 3-30 days after conidia challenge compared to the normal serum-treated group. Histological evidence showed retention of A. fumigatus conidia, airway remodeling, subepithelial fibrosis, and increased collagen deposition in the lungs of IL-18-depleted mice at day 30 after the conidia challenge. Prolonged retention of conidia in IL-18 depleted A. fumigatus sensitized mice was associated with decreased Toll-like receptor-2 (TLR-2) expression compared with the control group. CONCLUSIONS: IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease. PMID- 11766997 TI - Analysis of the mechanisms involved in the inflammatory response induced by des Arg9-bradykinin in the rat pleural cavity. AB - OBJECTIVE: The present study investigates some of the mechanisms underlying the inflammatory responses caused by the selective B1 kinin receptor agonist, des Arg9-bradykinin (des-Arg9-BK), in the rat pleural cavity. MATERIAL: Male Wistar rats were used (N = 4-10 per group). TREATMENT: A fixed volume (100 microl) of PBS or des-Arg9-BK (10-60 nmol) was injected into the rat pleural cavity. Animals were treated with the B1 des-Arg9[Leu8]-BK (60 nmol/cav.) and R715 (65 nmol/cav.), B2 HOE 140 (3 nmol/cav.), NK1 FK888 (1 nmol/cav.), NK2 SR 48968 (20 nmol/cav) or NK3 SR142801 (10 nmol/cav.) receptor antagonists, or with either cyproheptadine (40 mg/kg, i.p.) or compound 48/80 (0.6 mg/kg, i.p., twice a day/3 days, 1.2 mg/kg/4th day). RESULTS: des-Arg9-BK (30 nmol/cavity) induced a time dependent leukocyte migration. The increase in total leukocytes was not significantly reduced by the treatment with any of the B1, B2, NK1, NK2 or NK3 receptor antagonists. Treatment of animals with cyproheptadine or with compound 48/80 markedly inhibited des-Arg9-BK-induced cell migration (77 +/- 7 and 82 +/- 4%, respectively). CONCLUSION: These findings suggest that inflammatory responses caused by the B1 agonist des-Arg9-BK in the rat pleural cavity are mediated by a receptor-independent mechanism, being largely dependent on the activation of resident mast cells and release of histamine and/or serotonin. PMID- 11766998 TI - Site difference in RhoA expression between rat bronchial and tracheal smooth muscles after antigen challenge--relation to development of hyperresponsiveness. AB - OBJECTIVE: The present study compared the effects of repeated antigen exposure on the development of hyperresponsiveness and the expression of RhoA in the main bronchial and lower tracheal smooth muscles of sensitized METHODS: Actively sensitized rats were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge the isometrical contractions of the bronchial and tracheal smooth muscles were measured. Immunoblottings were also performed using bronchial and tracheal homogenates and the density ratios of RhoA/beta-actin were calculated to quantify the levels of RhoA. RESULTS: Acetylcholine-induced contraction of bronchial, but not tracheal, smooth muscle of antigen-treated rats was significantly augmented as compared with that of control rats, indicating that airway hyperresponsiveness appeared by antigen challenge in bronchial smooth muscle. RhoA expression in bronchial, but not tracheal, smooth muscle was significantly increased in the antigen-treated animals. CONCLUSION: The increased expression of RhoA is suggested to have an important role in developing hyperresponsiveness of bronchial smooth muscle. PMID- 11766999 TI - Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline. AB - In the context of chronic physical illness, such as breast cancer, depression is associated with increased morbidity, longer periods of hospitalization, and greater overall disability. Prompt diagnosis and effective treatment is. therefore, essential. Several small studies have established the efficacy of tricyclic antidepressants (TCAs) in this setting, and the selective serotonin reuptake inhibitors (SSRIs) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile. This was a multicenter. double-blind, parallel-group study in which 179 women with breast cancer were randomized to treatment with either the SSRI paroxetine (20-40 mg/day), or the TCA, amitriptyline (75-150 mg/day). After 8-weeks treatment, depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale. Clinical global impression (CGI) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint: a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale. A steady improvement in quality of life was also observed in both groups. There were no clinically significant differences between the groups. In total, 47 (53.4%) patients in the paroxetine group and 53 (59.6%) patients in the amitriptyline group had adverse experiences, the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy. Anticholinergic effects were almost twice as frequent in the amitriptyline group (19.1%) compared with paroxetine (11.4%). This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer. PMID- 11767000 TI - Cytotoxicity induced by manipulation of signal transduction pathways is associated with down-regulation of Bcl-2 but not Mcl-1 in MCF-7 human breast cancer. AB - We examined the role of Mcl-1 and Bcl-2 expression in the induction of apoptosis. through blocking protein tyrosine kinase (PTK), protein kinase C (PKC), phosphatidylinositol 3-kinase (P13-K) and mitogen-activated protein kinase (MAPK)/Erk kinase (MEK) signaling pathways by various kinase inhibitors in MCF-7 breast cancer cells. The PTK inhibitor genistein (GEN) and PKC inhibitor staurosporine (STP) down-regulated Mcl-1 and Bcl-2 expression, and induced growth inhibition by blocking at the G2/M phase of cell cycle, followed by apoptosis, leading to chromatin condensation and DNA fragmentation. LY294002 (LY)-mediated inhibition of P13-K activity down-regulated Bcl-2 but not Mcl-1 expression. triggered growth arrest at the G1/G0 phase of cell cycle and also led to apoptosis marked with chromatin condensation and DNA fragmentation. The MEK inhibitor U0126 (U0) decreased Bcl-2 expression but not Mcl-1 expression, inhibited cells growth and induced G1/G0 arrest. but in this case cell death occurred without significant apoptotic features. The kinase inhibitor concentration dependence of cytotoxicity correlated well with down-regulation of Bcl-2 but not with changes in Mcl-1 levels. This suggests that Bcl-2 plays a predominant role in the regulation of cell death induced by cell signaling alterations whereas Mcl-1 does not appear to control cell survival under these conditions in MCF-7 cells. Further studies showed that the combination of GEN, STP and LY with U0 can produce synergetic cytotoxic effects on MCF-7 cells. Our results suggest that PTK, PKC, P13-K and MEK signaling pathways can regulate Bcl 2 expression and form an integrated network that plays a critical role in cell survival. PMID- 11767001 TI - Estrogen and rapamycin effects on cell cycle progression in T47D breast cancer cells. AB - The contribution of estrogen (and progesterone) in driving cell cycle progression of hormone dependent breast cancer cells is well documented, however, the roles of the various relevant signal transduction pathways remain unclear. The immunosuppressant rapamycin is a potent inhibitor of cell cycle progression and has been used to define signal transduction pathways. In this study we have determined rapamycin's effects on cell cycle progression in estrogen dependent breast cancer cells using a novel method of inducing S-phase. In this method estradiol-17-beta alone induced S-phase without mitogen support. In our studies the T47D cells were quite sensitive to estradiol-17-beta, with half-maximal induction in the picomolar range. indicating that the estrogen can induce S-phase in the absence of mitogens such as insulin. The estrogen response does not seem to be particularly specific because estriol estrone and estradiol-17-beta-BSA were about as effective as estradiol-17-beta. R5020, a progestin also induced S Phase, while rapamycin blocked steroid driven transition of cells from G1 to S phase. PMID- 11767002 TI - Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor. AB - Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFbeta1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFbeta1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFbeta1 mRNA expression in the cells and enhanced the secretion of TGFbeta1 into culture medium. However, exogenous addition of TGFbeta1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFbeta1, did not reverse bFGF induced G1 arrest northe increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFbeta1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFbeta1, while exogenous TGFbeta1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells. PMID- 11767003 TI - Allelic loss of chromosome 3p24 correlates with tumor progression rather than with retinoic acid receptor beta2 expression in breast carcinoma. AB - A tumor suppressor gene. retinoic acid receptor (RAR) beta2, has been mapped to chromosome 3p24, a region where loss of heterozygosity (LOH) has been observed commonly in carcinomas of various tumor tissues. RAR beta2 expression is reduced or lost in many malignant tumors including breast cancer, however, whether LOH accounts for the loss of expression of RAR beta2 in breast cancer is unknown. We, therefore, assessed LOH on chromosome band 3p24 to correlate it with RAR beta2 expression and other established prognostic parameters in 52 breast carcinomas. Based on three microsatellites, D3S 1283, D3S 1293 and D3S 1286. all of the tumors were informative, of these, 12 (23%) exhibited LOH. RAR beta2 expression was lost in 42% (19/45) of these samples. We found that LOH on chromosome band 3p24 was not correlated with loss of RAR beta2, but correlated with higher histological grade, p53-positivity, and loss of estrogen and progesterone receptors. Our findings suggest that LOH of the RAR beta2 gene does not account for the frequent loss of RAR beta2 expression in breast cancer but the genomic structural alteration at or close to the RAR beta2 gene locus are likely to be associated with tumor progression and/or loss of hormonal dependency. PMID- 11767004 TI - The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue. AB - Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 (CYP) enzymes play a major role in the activation of these chemicals. Using highly specific and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. the expression profile of all major xenobiotic metabolizing CYP forms was screened in breast tumour and surrounding tumour free (control) breast tissue in a series of 20 sample pairs obtained from females with infiltrating ductal carcinoma. The levels of CYPIAI mRNA were very low in both tumour and normal tissue. CYP1B1, CYP2B6, CYP2C, CYP2D6, CYP2E1, CYP4B1, and CYP11A1 expressions were positive in both tumours and control tissue. CYP2A6, CYP2A7, CYP2A13, CYP2F1, CYP3A4, CYP3A5. and CYP3A7 mRNAs were expressed neither in tumours nor in control tissue. These results show that several CYPs. responsible for the activation of a quite large number of procarcinogens and genotoxic estrogen metabolites. are expressed in breast tissue with a lack of qualitative differences in CYP expression at mRNA level between breast tumours and surrounding normal breast. PMID- 11767005 TI - Angiogenesis as a predictor of long-term survival for 377 Japanese patients with breast cancer. AB - Angiogenesis. as assessed by microvessels, has been a common prognostic indicator for breast cancer in the last decade. However, the significance of angiogenesis remains controversial. This is a retrospective study of 377 Japanese patients selected from 663 breast cancer patients operated on between 1971 and 1987. To evaluate an objective method to quantify microvessel density in angiogenesis, we employed average microvessel count (AMC) per square millimeter. We investigated five factors: angiogenesis, lymph-node status (n), clinical tumor size (T), histological grade (HG). and tumor necrosis (TN), followed for a median of 10 years. Sixty-seven patients (17.8%) had recurrence and 54 patients (14.3%) died of breast cancer. Univariate analysis showed that n, T, HG. and AMC (P = 0.0020) were significantly predictive of 20-year relapse-free survival (RFS). n, T, and HG were significantly associated with 20-year overall survival (OS) but AMC was borderline significant (P = 0.0630). Multivariate analysis for RFS and OS showed that n. T. HG, and AMC (P < 0.0001, P = 0.0033, respectively) were all significant and independent prognostic factors. When stratified by T or n, a significant impact of AMC on RFS or OS was seen both in patients with T2 and T3 carcinomas or in node-negative patients, but not in T1 or node-positive patients. Thus, we can confirm angiogenesis as a significant independent prognostic factor associated with longterm survival in Japanese breast cancer patients, especially in node-negative patients and in patients with T2 and T3 carcinomas. PMID- 11767006 TI - Risk factors associated with the occurrence of bovine tuberculosis in cattle in the Southern Highlands of Tanzania. AB - A study was conducted in the Southern Highlands of Tanzania to determine the prevalence of bovine tuberculosis and the risk factors associated with the occurrence of the disease in cattle of different categories and in different climatic zones. The overall prevalence of the disease was 13.2%, and 51% of the herds tested contained reactor cattle. Assessment of risk factors was based on comparisons of the reactivity of the cattle in the single comparative intradermal tuberculin test (SCITT). Older cattle were more affected by the disease than yearlings and calves (p<0.0001). There were significant differences between male and female cattle (p<0.05) and between cattle with exotic blood compared to indigenous Short Horn Zebu (SHZ) cattle (p<0.05). The castrated bulls, often used for draught power, were more frequently (p<0.01) affected than the entire bulls, mainly used for breeding. Reactivity to tuberculin did not appear to be influenced by the reproductive status of the animal. The reactivity to tuberculin of pregnant cattle was not significantly different from that of the rest of the cows (p>0.05). However, significantly more (14.6%) lactating cattle reacted in the SCITT than did non-lactating cows (12.0%) (p<0.05). There was a highly significant difference (p<0.001) between reactivity in the SCITT among cattle grazing in the hot and dry lower lands (14.0%) and that in those grazing in the cool and wet highlands (8.7%). PMID- 11767007 TI - Feline ubiquitin fusion protein genes. AB - Using cDNA from a CRFK cell line as a template, PCR amplification was performed with the Ub1S and poly(dT) primers to isolate feline ubiquitin genes. Sequencing of the 495 bp PCR fragment revealed that the putative amino acids induced by this fragment gave a fusion protein consisting of a ubiquitin polypeptide (76 amino acids) and an extension protein of ribosomal proteins L40 (52 amino acids). The putative amino acid sequence of ubiquitin was identical to those of humans, rats and pigs. The recombinant glutathione S-transferase (GST)-feline ubiquitin fusion proteins were produced in Escherichia coli and purified. The fusion proteins had a molecular weight of about 42 kDa and were detected by immunoblot assay with rabbit anti-ubiquitin antiserum. The mRNAs from heat-shocked and non-heat-shocked cells were subjected to RT-PCR (Ub1S and poly(dT) primers) analysis. The molecular weights of the ubiquitinated proteins in heat-shocked CFRK cells were between 18 kDa and 24 kDa by immunoblot assay. These results suggested that there were more ubiquinated proteins in the heat-shocked CRFK cells than in the pre heat-shocked cells. PMID- 11767008 TI - Activities of enzymes in the malate-aspartate shuttle in the peripheral leukocytes of dogs and cats. AB - The activities of the enzymes involved in the malate-aspartate shuttle and the expression of malate dehydrogenase (MDH), a rate-limiting enzyme in the NADH shuttle that produces ATP in glucose metabolism in leukocytes, were determined to investigate the differences in this shuttle system in the peripheral leukocytes of dogs and cats. There were no significant differences between dogs and cats in plasma glucose, immunoreactive insulin, free fatty acid or triglyceride concentrations. The activities of cytosolic and mitochondrial MDH and of mitochondrial glutamate dehydrogenase (GLDH) in canine leukocytes were significantly higher than in feline leukocytes. High activities of MDH in canine leukocytes were confirmed by RT-PCR analysis on the total RNA extracted from leukocytes. It was concluded that there were significant differences between dogs and cats in the NADH shuttle system. PMID- 11767009 TI - Studies on the pathogenesis of shimao zheng (fleece-eating) in sheep and goats. AB - Research on the disease called shimao zheng, which had resulted in widespread fleece-eating and shedding by sheep and goats in the Haizi area of Akesa County of Gansu Province of China, was carried out by both laboratory studies and pathological observations. There was a marked deficiency of sulfur in the wool and tissues of the affected animals. The pathological changes were mainly loss of fleece, exposure of the skin, keratinization of the epidermal cells, narrowing and reduced numbers of the fleece follicles, and fewer sebaceous glands and sweat glands. Histologically, there was atrophy of the striated and cardiac muscles and of the epithelium of the convoluted tubules of the kidney, together with a glomerulonephritis. The disease was considered to be a local nutritional and metabolic disorder, probably mainly caused by sulfur deficiency. PMID- 11767010 TI - The disposition kinetics, urinary excretion and dosage regimen of ciprofloxacin in buffalo calves (Bubalus bubalis). AB - The disposition kinetics, urinary excretion and a dosage regimen for ciprofloxacin after a single intravenous administration of 5 mg/kg was investigated in 5 healthy buffalo calves. The disposition kinetics were best fitted to a three-compartment open model. After 1 min, the concentration of ciprofloxacin in plasma was 8.50 +/- 0.39 microg/ml and the minimum therapeutic concentration was maintained for 10 h. The elimination half-life and volume of distribution were 3.88 and 0.08 h and 3.97 +/- 0.22 L/kg, respectively. The total body clearance and T/P ratio were 0.709 +/- 0.025 L/kg per h and 6.13 +/- 0.54, respectively. Approximately 28.3% of the total administered dose of ciprofloxacin was recovered in urine within 24 h of administration. To maintain a minimum therapeutic plasma concentration of 0.10 microg/ml, a satisfactory intravenous dosage regimen of ciprofloxacin, computed on the basis of disposition kinetic data obtained in healthy buffalo calves, would be 3 mg/kg repeated at 12 h intervals. PMID- 11767011 TI - Transference of dietary veterinary drugs into eggs. AB - Twelve veterinary drugs, bacitracin (BC), chloramphenicol (CAP), chlortetracycline (CTC), oxytetracycline (OTC), tylosin (TS), amprolium (APL), furazolidone (FZD), nicarbazine (NCZ), ormetoprium (OMP), sulfadimidine (SDD), sulfadimethoxine (SDM) and sulfamonomethoxine (SMM) were fed to laying hens for 14 days, each at a dietary concentration of 500 mg/kg. The concentrations of the drugs in the eggs from these birds were determined at 2-day intervals for 14 days after the start of feeding. The relationship between the concentrations of the drugs (mg/kg) in the eggs and the number of days after the start of feeding was analysed by regression and covariance analyses. The concentrations of the drugs in the eggs became constant after 4 days for OTC, TS, FZD and all the sulfonamides, and after 6 days for CAP, APL, NCZ and OMP. No BC or CTC was detected in the eggs. The transfer rates of the 10 drugs (excluding BC and CTC) from the feed to eggs varied from 0.005% for TS up to 1.540% for SDD. PMID- 11767012 TI - Bovine immunodeficiency virus in relation to embryos fertilized in vitro. AB - The association of bovine immunodeficiency virus (BIV) with embryos derived by in vitro fertilization from oocytes of experimentally infected heifers or oocytes/embryos exposed to the virus in vitro was investigated. Using a nested PCR assay, proviral DNA of BIV was not detected in follicular fluid or in embryos derived from BIV-infected donors. In vitro exposure of oocytes to BIV during maturation or insemination with BIV-infected semen resulted in zona pellucida intact embryos testing negative for BIV provirus. However, exposure of zona pellucida-free day-7 embryos to the virus resulted in a positive BIV assay for 28% of the batches of embryos, suggesting that the zona pellucida has a role in protecting against BIV infection. The presence of BIV in the IVF system had no apparent effect on the development of bovine embryos to the blastocyst stage. PMID- 11767013 TI - Neutralizing and complement-fixing monoclonal antibodies as an aid to the diagnosis of equine herpesvirus-1 infection. AB - One complement-fixing (C-MAb) and three complement-dependent neutralizing monoclonal antibodies (N-MAbs) were raised against Hisar-90-7 equine herpesvirus 1 (EHV-1) strain. The target antigen of the C-MAb (2A5) and two of the N-MAbs (1H6, 9C4) was identified as a 140 kDa polypeptide in Western blotting. The target antigen of N-MAb (9C6) could not be identified. Purified polypeptides of five EHV-1 strains isolated from different regions and at different times gave intense bands at 140 kDa when reacted with N-MAb (1H6) in Western blots. In sandwich ELISA, all four MAbs captured the viral antigen from clinical materials, giving a reliable and rapid diagnosis of EHV-1 infection in equines. PMID- 11767014 TI - Trabeculectomy in the UK: is there room for improvement? PMID- 11767015 TI - Needle local anaesthesia for cataract surgery: a chip off the old block? PMID- 11767016 TI - The National Survey of Trabeculectomy. II. Variations in operative technique and outcome. AB - PURPOSE: There is a considerable body of literature relating to trabeculectomy; however, there are no data representative of the national experience of trabeculectomy in the United Kingdom (UK). The Department of Health funded a national survey of trabeculectomy to establish current practice patterns and the outcome of trabeculectomy in the National Health Service (NHS). In this paper we report variations in surgical technique and the national success rate of trabeculectomy. METHODS: A cross-sectional survey was carried out of consultant ophthalmologists performing trabeculectomy in the NHS. Participants recruited their four most recent consecutive first-time trabeculectomy cases according to study eligibility criteria and data were collected by self-administered questionnaire. FOLLOW-UP: 1 year post-trabeculectomy. Main outcome measure of success: final intraocular pressure (IOP) less than two-thirds the pre-operative IOP. Secondary outcome measures of success: final IOP less than 21 mmHg and visual field stability. Success was further defined as unqualified (excluding patients on anti-glaucoma medications at final follow-up) or qualified (including patients on anti-glaucoma medications at final follow-up). The relationship between variables characterising consultants' practice and main outcome measure was examined by chi-square test. RESULTS: Clinical outcome data were available for 1240 (85.3%) cases. There were wide variations in operative technique. The mean post-operative IOP was 14.4 mmHg (95% CI 14.2-14.7), which is a mean reduction of 11.8 mmHg (95% CI 11.4-12.2). An unqualified success, in terms of the main outcome measure, was achieved in 66.6% of patients and a qualified success in 71.0% of cases. An unqualified success, in terms of a final IOP less than 21 mmHg, was achieved in 84.0% of cases and a qualified success in 92.0%. Visual fields were stable in 84.2%. Outcome was not related to consultants' specialist interest, level of activity, type of hospital or region. CONCLUSIONS: The success rates reported in this paper represent the national experience of first-time trabeculectomy for open angle glaucoma in the UK. The national success rate at 1 year compares favourably with many studies in the literature. This survey provides valid and clinically relevant measures of success for the production of guidelines and standards for audit at regional, local and individual level and a baseline for the comparison of new therapies. PMID- 11767017 TI - Is the role of trabeculectomy in glaucoma management changing? AB - BACKGROUND: In recent years there have been significant developments in the diagnosis and treatment of glaucoma. We conducted a study to determine whether there has been an associated change in trabeculectomy rates in England over this period. METHODS: Figures for the total number of trabeculectomies and cataract operations performed in England for each year from 1989/90 to 1999/2000 were obtained from the Department of Health, Hospital Episode Statistics Division. RESULTS: The available data show that the number of trabeculectomies and cataract operations increased year on year from 1990/91 until 1995/96. Since then, the number of cataract procedures has continued to rise dramatically, whereas the number of trabeculectomies has fallen progressively by 7%, 23%, 37% and 53% in the last 4 years. CONCLUSION: The perceived need for surgical intervention would appear to have been delayed or prevented. We postulate that several factors underlie this trend and that there are a number of implications regarding the future management of glaucoma patients. PMID- 11767018 TI - Pupillary distortion and staphyloma following trans-scleral contact diode laser cyclophotocoagulation: a clinicopathological study of three patients. AB - PURPOSE: To search for the cause of scleral thinning and pupillary distortion following trans-scleral contact diode laser cyclophotocoagulation (TCDLC). METHODS: We reviewed the records of 3 patients in whom there were complications of scleral thinning and pupillary distortion following TCDLC. One of the eyes was later enucleated, and we present the histopathological findings. Using the histopathological features in this patient, we discuss the possible pathogenesis of the scleral thinning and pupillary distortion. RESULTS: Case 1 is a 46-year old white woman who following TCDLC in an area of clinically normal sclera developed a staphyloma. Case 2 is a 52-year-old white woman who following TCDLC in an area of scarred sclera developed mild thinning. Case 3 is an 85-year-old white man who following TCDLC developed pupillary distortion, and gonioscopy revealed damage to the peripheral iris. Histological examination of case 1 revealed the staphyloma covered by a thin layer of conjunctival epithelium, collagen and vitreous condensation. We also observed cicatricial cilary body contraction causing distortion of the pupil and lens. CONCLUSIONS: Therapeutic TCDLC can produce scarring of the iris root, anterior chamber angle, draining structures and ciliary body, and may result in pupillary distortion. Pre-existing scleral scars may predispose to scleral damage following TCDLC. We discuss a simple strategy to avoid this complication of TCDLC. PMID- 11767019 TI - Do locally agreed guidelines for optometrists concerning the referral of glaucoma suspects influence referral practice? AB - PURPOSE: To assess whether the issuing of local guidelines for glaucoma detection including a protocol for the referral of suspects can improve the quality and accuracy of referrals from optometrists. METHODS: Universally agreed guidelines, which included a protocol for referring glaucoma suspects, were circulated to all optometrists in the catchment area of a major teaching hospital ophthalmic unit. Data on 207 new patients referred to one glaucoma clinic were collected from GOS18 forms and hospital records covering two 12 month periods spanning the guideline dissemination. Referral accuracy was calculated and the reasons for protocol violations and referral of normal individuals were determined. Where possible, data were compared with a similar study relating to referrals made to the same clinic in 1988 and 1993. RESULTS: The mean (SD) intraocular pressure (IOP) at which optometrists referred patients was 22.5 (6.6) in 1997 and 21.9 mmHg (6.6) in 1998/9, both significantly less than in 1988. A statistically significant upward trend with time was found in the number of patients referred with an assessment of cup/disc ratio and in those with details of a visual field assessment. The overall 'true positive diagnosis' was 40% (42/105) in 1997 and 32.3% (33/102) in 1998/9 after the guidelines (p = 0.32), both of which were significantly lower than the 1988 rate of 56% (34/75) (p = 0.03 and 0.003). Fifty per cent of false positive referrals in both 1997 and 1998/9 were associated with an assessment by the optometrist of the optic disc(s) that was at variance with the ophthalmologist's. False positive visual fields were associated with 22% and 35% of non-true positive referrals in 1997 and 1998/9. Protocol violations were observed in 48% of referrals after the guidelines had been disseminated. When the referral was both a false positive and the guideline protocol was not followed, 88% of violations were associated with IOP measurement in 1997 and 73% in 1998/9. The equivalent figures for visual field violations were 70% in 1997 and 76% in 1998/9. Normal individuals referred as suspects were significantly (p = 0.001) less likely to be referred on IOP grounds if their optometrist followed the referral protocol. CONCLUSION: Local dissemination of glaucoma screening guidelines with a protocol for referral did not appear to improve the diagnostic accuracy of optometrists in our area. Optometrists who follow the guidelines refer fewer normal individuals on IOP grounds, but false positive visual fields and optic disc interpretation difficulties remain a factor in such referrals. Additional strategies will be necessary to improve the quality and accuracy of referrals for suspect glaucoma by optometrists. PMID- 11767020 TI - A single-centre study of 1000 consecutive peribulbar blocks. AB - PURPOSE: To assess the efficacy and safety of the peribulbar block as practised by anaesthetists in a District General Hospital and also to assess the effect of using the 'painless local' subconjunctival injection on the pain of the peribulbar block. METHOD: Audit data collected from 1000 consecutive patients undergoing peribulbar blocks with 2% lignocaine were analysed. Efficacy was assessed by visual rating scores for operative pain, eye movement, intraocular pressure and reinjection rate, and safety by looking at complications. Comparison of pain of injection scores was used to assess the effect of the 'painless local' injection. Visual rating scores for pain were analysed using the Mann-Whitney U test. RESULTS: Akinesia was achieved in 79% of blocks and operative pain scores were very low (median = 0, IQR = 0). All complications recorded were minor and there were no sight- or life-threatening events. The 'painless local' injection given to 499 patients resulted in significantly lower visual rating scores for pain of injection (p<0.05). CONCLUSION: These data suggest that the peribulbar block is a safe and effective method of providing anaesthesia for eye surgery provided that it is taught methodically and practised by experienced staff. The 'painless local' injection reduces the pain experienced during administration of this block. PMID- 11767021 TI - Optic neuritis in an urban black African community. AB - PURPOSE: To describe the clinical profile of idiopathic optic neuritis in South African blacks. METHODS: South African black patients with acute isolated idiopathic optic neuritis, treated and followed for at least 3 months at a large medical centre, were studied. Exclusion criteria were other causes of optic neuropathy (such as ischaemic optic neuropathy, toxins or Leber's hereditary optic neuropathy); all causes of optic neuritis (such as HIV, neurosyphilis, sarcoid or connective tissue disease); neurological disease outside of the optic nerves; and any race other than South African black. Patients underwent extensive ophthalmic, neurological, radiological, cerebrospinal fluid and blood assessment. RESULTS: Eighteen eyes of 10 patients were studied. The mean age was 35.7 years and 9 patients were female. Only 2 patients had truly unilateral optic neuritis, the other 8 having either bilaterally simultaneous or consecutive disease. Presenting visual acuity (VA) was less than 6/60 in 17 of 18 eyes, with severe dyschromatopsia in all eyes. Fifteen eyes had optic disc swelling. All patients were treated with corticosteroids. After at least 3 months follow-up only 6 eyes recovered VA of 6/12 or better, with only 3 eyes recovering colour vision of 10/13 or better on Ishihara plate testing. No patient had multiple sclerosis (MS) on presentation, nor developed MS on follow-up. CONCLUSION: Idiopathic optic neuritis in black South Africans differs from that in whites. The higher prevalence of bilateral cases and of optic disc swelling, the weaker association with MS and the extremely poor visual outcome distinguish optic neuritis in black South Africans. PMID- 11767022 TI - Failure of accommodation in patients with HIV infection. AB - PURPOSE: The principal objective was to test the hypothesis that HIV-positive patients have significantly reduced amplitudes of accommodation compared with controls. The secondary objective was to investigate accommodative impairment in relation to factors such as age of susceptibility, CD4 count, viral load and current antiretroviral therapies. METHOD: The study was a single-center open prospective study involving a subject population of 43 HIV-positive men aged from 26 to 39 years with no previous history of eye problems and 21 age-matched healthy male controls. The main outcome measure was the amplitude of accommodation, as measured monocularly with a standard push-up technique. RESULTS: Amplitudes of accommodation were significantly smaller in the HIV positive group compared with controls for age groups 25-29 (p = 0.016) and 30-34 years (p = 0.030) but not in the older group. In total, 30% (8/27) of patients aged between 25 and 34 years had reduced amplitudes of accommodation below age expected norms. Accommodative failure was not related to current or lowest CD4 count, viral load or specific antiretroviral therapies. CONCLUSION: This study has identified accommodative failure in a significant proportion of HIV-positive patients aged between 26 and 35 years. This problem may be under-recognised, and further studies are warranted to investigate possible causes. PMID- 11767023 TI - Autosomal dominant congenital superior oblique palsy. AB - PURPOSE: We describe a mother and all her offspring with congenital superior oblique palsy (CSOP), and a father and all his sons with unilateral CSOP. We discuss the inheritance pattern in our pedigrees and compare it with previous reports. METHOD: All available family members were examined. The prism cover test was performed. Ocular movements were examined in all positions of gaze and where possible a Hess chart plotted. Lang and TNO stereotests were used to determine the stereo-acuity. The results of these tests combined with the Bielschowsky head tilt test (BHTT) were used to confirm the diagnosis of superior oblique palsy. The condition was classified as congenital if it presented early based on history or the observation of old photographs and in the absence of a causative factor. RESULTS: The affected members of family A consist of a father and his three sons with unilateral CSOP. His daughter had a mild weakness of her left inferior and superior rectus muscle. One of his sons was asymptomatic and only recognised on screening of the family for the study. The affected members of family B consist of a mother and her younger daughter with unilateral CSOP and her older daughter with bilateral CSOP. She had no other children. CONCLUSIONS: Our families demonstrate what is probably an autosomal dominant form of CSOP. It is possible that hereditary CSOP is more common than previously reported. PMID- 11767024 TI - Does neonatal ocular misalignment predict later abnormality? AB - PURPOSE: A longitudinal prospective study was carried out to ascertain the significance of neonatal ocular misalignments. METHODS: Pre-school vision screening and hospital records were examined to determine the visual outcome of 1150 infants classified into 'often' (> 15% of waking hours), 'occasionally' (< 15%) or 'never' having an ocular misalignment (neonatal squint) in the first 8 weeks of life. Chi2 and Fisher's exact tests and ANOVA were used to analyse the data. RESULTS: When compared with infants who had squinted occasionally or never, frequent squinting in the neonatal period (which occurred in 7.7% of the subjects) was significantly associated with having been prescribed spectacles (p = 0.04), both for hypermetropia (p = 0.04) and for myopia (p = 0.05). Frequent squinters also had a higher incidence of significant esodeviation (p = 0.04) and were more likely to be > 21 days premature (p = 0.05). Small numbers of abnormalities made statistical analysis limited, but there were weak trends towards more myopic and oblique astigmatism in the 'never' group. The esotropias in the 'often' group were more frequently intermittent than those found in the other groups. CONCLUSIONS: Occasional squinting in the first 8 weeks of life appears to be normal neonatal behaviour. Frequent squinting trebles the chances of developing a significant esodeviation or refractive error severe enough to require spectacles before 5 years of age but incidence of abnormality still does not exceed 9%. PMID- 11767025 TI - Does the shared epitope genotype influence either the susceptibility to or the phenotype of corneal melting? AB - PURPOSE: To investigate the role of the shared epitope alleles in determining susceptibility to and the phenotype of corneal melting in patients with rheumatoid arthritis (RA). METHODS: The HLA class 1 and 2 genotype was determined for 17 patients with rheumatoid-associated comeal melting by the phototyping method. HLA-DR4 subtyping was performed by PCR sequence-based typing. The frequency of all the shared epitope alleles and, in particular, of the higher risk *0401 and *0404 alleles, was compared with healthy controls and unrelated RA patients, with and without extra-articular manifestations. A comparison was also made between the shared epitope genotype of the corneal melt patients and local, ocular disease characteristics. RESULTS: Thirteen (76%) patients with corneal melt possessed at least one shared epitope allele and 5 (29%) possessed two alleles. The dominant alleles were variants of the DR4 family, notably the *0401, *0404 and *0408 alleles. Both the allele frequency and a double dose of shared epitope alleles were more common in the three RA patient groups than in the healthy, control group (p < 0.005). Although the frequency of the higher-risk alleles was similar in the three RA patient group, a trend existed for a double dose of higher-risk alleles to be more common in the patients with either corneal melt or other extra-articular manifestations (p > 0.2). No association was found between the number or type of shared epitope alleles and any of the ocular disease characteristics studied. CONCLUSIONS: The results of this study suggest that the shared epitope alleles do not influence the ocular disease phenotype of corneal melt in RA patients. Shared epitope determination of RA patients may help to identify those susceptible to either corneal melt or other extra-articular disease. RA patients with a double dose of higher-risk alleles may have an increased risk of corneal melt. PMID- 11767026 TI - The use of intravitreal gases in non-vitrectomised eyes. PMID- 11767027 TI - Effect of sildenafil on ocular haemodynamics. AB - PURPOSE: To study the effect of sildenafil, which is an effective agent for the treatment of erectile dysfunction, on ocular haemodynamics. METHODS: In this prospective study we examined the effect of a single oral dose of 50 mg sildenafil (Viagra) in a group of healthy young male volunteers, by using colour Doppler ultrasound imaging to measure haemodynamic variables in the central retinal artery (CRA), short temporal posterior ciliary artery (STPCA) and ophthalmic artery (OA). The following examinations were performed on both eyes immediately before and 1 h after a single oral dose of 50 mg sildenafil: visual acuity, intraocular pressure (IOP), colour vision, anterior segment, fundus appearance, resting heart rate, blood pressure and colour Doppler measurements. RESULTS: After sildenafil administration, peak systolic velocity, mean velocity and end-diastolic velocity significantly increased in the OA of both eyes. All Dopper indices remained non-significant for the CRA and STPCA of both eyes. Sildenafil did not cause any significant change in IOP, colour vision, visual acuity, systolic blood pressure or diastolic blood pressure. However, heart rate measurements increased significantly after sildenafil administration compared with baseline (p = 0.003). CONCLUSION: The increased flow velocity in the ophthalmic artery seems to be due to a vasodilator effect of sildenafil. PMID- 11767028 TI - Thrombophilia as a cause for central and branch retinal artery occlusion in patients without an apparent embolic source. AB - PURPOSE: To assess the prevalence of vascular risk factors and thrombophilias in central and branch retinal artery occlusion in patients in whom an embolic source is not apparent. METHODS: The study group consisted of 21 consecutive patients with retinal artery occlusion (RAO) in whom Doppler ultrasonography of the carotid arteries and transthoracic or transoesophageal echocardiography were normal. Laboratory methods included polymerase chain reaction for detection of factor V G1691A, factor II G20210A and methylentetrahydrofolate reductase C677T mutations, assays of plasma levels of protein C, free protein S, antithrombin, fibrinogen and homocysteine; and tests for the presence of lupus anticoagulant and anticardiolipin antibodies. Controls for the laboratory tests were 243 healthy subjects. RESULTS: Nine of the 21 (43%) patients had at least one thrombophilic marker: 4 were homozygous for MTHFR C677T, 1 was heterozygous for factor V G1691A, 1 had a high titre of IgM anticardiolipin, 2 were heterozygous for factor V G1691A and homozygous for MTHFR C677T, and 1 had lupus anticoagulant, a high titre of IgM anticardiolipin, homozygosity for MTHFR C677T and hyperhomocysteinaemia. An interaction between vascular risk factors and thrombophilias seemed important since out of 14 patients with hypertension, diabetes and/or hypercholesterolaemia 7 (50%) had a thrombophilia. Homozygous MTHFR C677T was a significant risk factor with odds ratio of 3.18 (95% CI 1.20 8.47). The prevalence of factor V G1691A was also higher in the RAO patients versus controls with an odds ratio of 2.36 (95% CI 0.63-8.88), but this value did not reach significance, probably due to the small sample size. CONCLUSION: A search for thrombophilia in RAO is advisable in patients without evident source of emboli even when vascular risk factors are identified. PMID- 11767029 TI - Indocyanine green augmented transpupillary thermotherapy in the management of choroidal metastasis from breast carcinoma. AB - PURPOSE: To demonstrate the efficacy of indocyanine green augmented transpupillary thermotherapy (TTT) in the management of choroidal metastasis from breast carcinoma. METHODS: A retrospective study was performed on 4 women aged 39 59 years with solitary choroidal metastasis from breast carcinoma in whom choroidal metastasis was managed using mTT. All patients had undergone indocyanine green (ICG) augmented TTT using a diode laser (810 nm) treatment to these lesions and had a mean post-treatment follow-up of 13.2 months. RESULTS: In all the patients there was a gradual regression of the lesion over a mean follow up of 13.2 months with retention of good visual acuity. CONCLUSION: Indocyanine green augmented transpupillary thermotherapy is a viable alternative for management of solitary choroidal metastasis from breast carcinoma. PMID- 11767030 TI - Nd:YAG laser treatment for premacular subhyaloid haemorrhage. AB - PURPOSE: Premacular subhyaloid haemorrhage produces sudden, profound visual loss which may be prolonged if untreated. Nd:YAG laser treatment can create a posterior hyaloidotomy enabling rapid diffusion of subhyaloid haemorrhage into the vitreous gel. This study was performed to assess the results of Nd:YAG laser hyaloidotomy and to compare the outcome with similar conservatively managed cases. METHODS: Nd:YAG laser hyaloidotomy was performed in 6 patients with premacular subhyaloid haemorrhage. The aetiologies were Valsalva retinopathy, macroaneurysm, branch retinal vein occlusion, proliferative diabetic retinopathy (2 cases) and idiopathic. Four patients with premacular subhyaloid haemorrhage were managed conservatively. The aetiologies were Valsalva retinopathy (2 cases), macroaneurysm and proliferative diabetic retinopathy. RESULTS: Nd:YAG laser hyaloidotomy achieved rapid resolution of subhyaloid haemorrhage in all treated patients. Visual acuity improved to 6/9 or better in 4 patients, but was limited by ischaemic diabetic retinopathy in 2 patients. No patient had evidence of damage to the retina or choroid from treatment. Among the conservatively managed cases, 3 patients had slow resolution of the subhyaloid haemorrhage over 3-6 months. One patient with diabetic retinopathy demonstrated little improvement at 18 months. CONCLUSION: Nd:YAG laser hyaloidotomy is a safe and effective procedure. It achieves rapid resolution of premacular subhyaloid haemorrhage with restoration of visual function, preventing the need for vitreoretinal surgery. PMID- 11767031 TI - Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. AB - PURPOSE: To assess the long-term efficacy of combined vitamin A and E treatment in preventing retinal degeneration in patients with abetalipoproteinaemia (ABL) or homozygous hypobetalipoproteinaemia (HBL). METHODS: Ten patients with ABL and 3 with homozygous HBL who were treated with oral supplements of vitamins A and E were studied. Systemic, ophthalmological and electroretinographic follow-up for a mean of 11.7 years (range 4-20 years) after onset of treatment was evaluated. RESULTS: Despite vitamin A and E treatment, 7 of 10 patients who began treatment prior to 2 years of age and all 3 patients who began treatment later in life manifested unusual fundoscopic pigmentary changes over time. At the end of follow up, 11 of 13 patients had subnormal mixed cone-rod electroretinogram amplitudes. Seven of 10 patients for whom perimetry was available had mild to severe constriction of the visual fields. CONCLUSIONS: Combined oral vitamin A and E supplementation that is initiated prior to 2 years of age can markedly attenuate the severe retinal degeneration that is associated with untreated ABL or homozygous HBL. Yet, fundoscopic and functional retinal changes do occur despite early initiation of vitamin treatment. Therefore, the adequacy of the present treatment protocol for ABL and homozygous HBL should be re-evaluated. PMID- 11767032 TI - Retinal vascular architecture is maintained in retinal degeneration: corrosion cast and electron microscope study. AB - PURPOSE: To demonstrate the changes of the retinal vascular architecture in the diffusely degenerated thin retina. METHODS: Three-week-old weanling Wistar Kyoto rats were divided randomly into two groups. One group (n = 20) was fed a vitamin E-deficient solid diet and the other group (n = 20) was fed a solid rat chow diet. Rats were maintained on their respective diets for 14 months and then killed for scanning electron microscopy of vascular corrosion casts, light and electron microscopy and biochemical determinations. RESULTS: The serum level of vitamin E in the E-deficient rats was 1.0 +/- 0.49 microg/ml, while that in the rats fed a normal diet was 13.7 +/- 1.0 microg/ml (Student's t-test, p = 0.0001). In vitamin E-deficient rats, light microscopy showed degenerated retinas only half as thick as normal. Corrosion casts and scanning electron microscopy revealed that the retinal capillaries of the entire retina were decreased in number and scattered with localised narrowing, calibre irregularity and frequent loop formation. In the posterior pole of the retina, some capillaries clustered into small tortuous knots. However, the two-layered architecture of the capillary network in the retina was maintained. The differences in calibre of retinal capillaries between the vitamin E-deficient and normal rats were statistically significant (p < 0.0001). No remarkable abnormal changes were observed in the large retinal vessels other than arterial calibre differences (p < 0.022). No arteriovenous shunts, crossing defects or microaneurysms were seen. Transmission electron microscopy revealed complete disappearance of the photoreceptor outer and inner segments and nuclei. The retinal pigment epithelium contained lipofuscin granules and retinal capillaries with narrow lumens. The capillary endothelial cells were thickened and had scarce cytoplasmic components with vacuoles and irregularly thickened basement membranes. The capillary pericytes had vacuoles. No abnormalities were seen in the control normal rats. CONCLUSION: These findings indicate that the decrease in retinal capillaries in vitamin E deficient rats is secondary to retinal degeneration. It was assumed that the morphological changes in the capillary network reflected structural damage to the retinal vascular cells caused by free radicals and lipid peroxides generated by oxidation. However, even in such severe degeneration the retinal vascular architecture, including the main artery and vein and two-layer capillary networks, was maintained. This is may be because of the basic anatomical arrangement of the blood vessels. PMID- 11767033 TI - How reliable are slit lamp biomicroscopy measurements of anterior segment structures? PMID- 11767034 TI - Fine needle aspiration biopsy: an investigative tool for iris metastasis. PMID- 11767035 TI - Supraventricular ectopics and supraventricular tachycardia following injection of subconjunctival Mydricaine No. 2. PMID- 11767036 TI - Leber's hereditary optic neuropathy following trauma. PMID- 11767037 TI - Episcleral osseous choristoma. PMID- 11767038 TI - Symptomatic arachnoid cyst presenting as a sixth nerve palsy. PMID- 11767039 TI - Massive extraocular extension as the presenting feature of a choroidal melanoma. PMID- 11767040 TI - A case of epiphora associated with Urbach-Wiethe syndrome. PMID- 11767041 TI - Spontaneous perforation of the globe in Ehlers Danlos syndrome. PMID- 11767042 TI - Orbital cellulitis following corneal gluing under sub-Tenon's local anaesthesia. PMID- 11767043 TI - Keratoconus associated with a chromosome 7,11 translocation. PMID- 11767044 TI - Scleritis as the presenting sign of primary antiphospholipid syndrome. PMID- 11767045 TI - Recurrent cerebral lupus heralded by an unusual combination of ocular manifestations. PMID- 11767046 TI - Bilateral reactive subretinal abscesses following S. pyogenes septicaemia. PMID- 11767047 TI - Coats' disease and Duchenne muscular dystrophy. PMID- 11767048 TI - Genetic variation of the nucleocapsid genes of waterfowl parvovirus. AB - Duck parvovirus (DPV) and Goose parvovirus (GPV) isolated from infected waterfowls with Derzsy's disease in the year 1999 were identified by polymerase chain reaction and sequencing. The nucleotide sequences of their viral capsid proteins (VPs) show that they share 77% similarity at the DNA, and 84.6% at the protein level. The most variable region between DPV and GPV resides in the N terminal of VP2 before the initiation codon of VP3 with 35% (19/54) amino acids divergence. Viral capsid protein sequences diverge 4.1 to 4.4% among 1990-99 isolated strains. Variant amino acids cluster in the common regions of VP3 at residues 203-266 and 482-534 which overlaps with the regions proposed to expose on the outer surfaces of parvoviral particles, implying that selective pressure from host immune system might play a part. These data provide useful information for antigenic epitope prediction. This study also reveal the presence of conserved strain-specific residues in VPs and these residues seldom vary among different viral isolates, suggesting that they might be functionally important and worth further investigation. PMID- 11767049 TI - Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome. AB - Fibrotic degeneration was examined in the kidneys of ICR-derived glomerulonephritis (ICGN) mice, a novel inbred mouse line with a hereditary nephrotic syndrome of unknown etiology considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we histochemically revealed changes in accumulation of extracellular matrix (ECM) components and in localization of integrins, cellular receptors for ECM, in the kidneys of ICGN mice with the progression of renal failure. Excessive accumulation of basement membrane (laminin and collagen IV) and interstitial (type III collagen) ECM components were demonstrated in the glomeruli and tubulointerstitum of ICGN mice. Marked deposition of type I collagen and tenascin was seen only in the glomeruli of ICGN mice but not in those of ICR mice as normal controls. Increased expression of integrin alpha1-, alpha2-, alpha5- and beta1-subunits in glomeruli with fibrotic degeneration and abnormal distribution of alpha6-subunit were noted in the kidneys of ICGN mice. Excessive laminin, a ligand of alpha6beta1-integrin, was demonstrated on the tubular basement membrane, but alpha6-subunit diffusely disappeared on the basal side of the tubular epithelial cells. We presumed that abnormal integrin expression in renal tubules causes epithelial cell detachment, and consequently tubular nephropathy, and results in disorder of ECM metabolism causing excessive accumulation of ECM components in the kidneys of ICGN mice. PMID- 11767050 TI - Modulatory effects of ionized alkali mineral complex (IAMC) on mRNA expression of porcine cytokines. AB - It has been recognized that ionized alkali mineral complex (IAMC)-fed farm animals demonstrate higher weight gains but less incidence of diseases than the unfed ones. However, how these beneficial effects in the IAMC-fed animals are induced has not yet been elucidated clearly. In this study, porcine peripheral blood mononuclear cells (PBMC) were cultured for 4, 24, and 48 hr in the presence of IAMC, and the effects of IAMC on mRNA expression of porcine cytokines were evaluated via a reverse transcription-polymerase chain reaction (RT-PCR). Expression levels of IL-4, IL-6, and IL-10 in IAMC-treated cells were usually higher than those in the untreated ones. However, IAMC-treated cells demonstrated a reduced expression of IL-2. In addition, expression of IFN-gamma was generally reduced in the cells treated with IAMC. The expression of IL-12 p35 and IL-12 p40 was not detectable in both the untreated and the IAMC-treated cells. Therefore, these results indicate that IAMC has immunomodulatory effects in vitro on the expression of porcine Th1-and Th2-type cytokines. PMID- 11767051 TI - Effects and neuro-toxic mechanisms of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl and endosulfan in neuronal stem cells. AB - Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (Juberg, 2000). These chemicals have adverse effects not only in the reproductive system but also in the central nervous system during development and throughout life. Polychlorinated biphenyls (PCBs) are a class of environmentally persistent and widespread halogenated hydrocarbons. It has been reported that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton, and fruits. To determine the effect of 2, 2', 4, 4', 5, 5',-hexachlorobiphenyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neural stem cells from rat brain at embryonic day 17. Isolated neural stem cells showed pluripotenty. Stem cells could differentiate into neurons and glia. Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it appeared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAPK) and gap junctional intercellular communication (GJIC). Endosulfan decreased the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfer (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and endosulfan may inhibit differentiation and proliferation of neural stem cells and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis. PMID- 11767052 TI - Population study and validation of paternity testing for Thoroughbred horses by 15 microsatellite loci. AB - Microsatellite 15 TKY System was characterized for parentage verification of horse registry. The Microsatellite 15 TKY System was constructed by using 15 microsatellites, TKY279, TKY287, TKY294, TKY297, TKY301, TKY312, TKY321, TKY325, TKY333, TKY337, TKY341, TKY343, TKY344, TKY374, and TKY394, to provide stringent PCR-based microsatellite typing specifically optimized for multicolor fluorescence detection. The Microsatellite 15 TKY System showed good resolutions for 250 unrelated Thoroughbred horses, and the probability of exclusion (PE) at each microsatellite ranged from 0.437 to 0.621, resulting in a total PE value of 99.998% for Thoroughbred horses. These results indicated that the Microsatellite 15 TKY System is useful for paternity testing of Thoroughbred horses. A paternity testing case for a Thoroughbred horse family, in which candidate sires had close relations, was analyzed using the Microsatellite 15 TKY System. In this case, the Microsatellite 15 TKY System excluded paternity of a false sire. We concluded that the Microsatellite 15 TKY System can give sufficient and reliable information for paternity testing. PMID- 11767053 TI - Plasma digoxin concentration in dogs with mitral regurgitation. AB - Fifteen and eight mature beagles, without (normal group) and with experimental mitral regurgitation (MR group), respectively, were given 0.02 mg/kg/day digoxin powder for 10 days orally. The optimum time for sample collection after administration of digoxin was observed to be 8-18 hr and 10-22 hr in the normal and MR groups, respectively. In both groups, a stable concentration was reached after 3-5 days of treatment. No differences in plasma level were observed between sexes. The optimum concentration of digoxin was attained at an earlier stage than has been previously reported for both dogs and humans. PMID- 11767054 TI - Analysis of open reading frame 5 in Japanese porcine reproductive and respiratory syndrome virus isolates by restriction fragment length polymorphism. AB - For the epidemiological survey of porcine reproductive and respiratory syndrome virus (PRRSV) isolated in Japan, the open reading frame (ORF) 5 gene of 37 field isolates in Chiba prefecture from 1991 to 1999 were analyzed by restriction fragment length polymorphism (RFLP). Reverse tanscription-polymerase chain reaction (RT-PCR) amplifying the ORF 5 gene detected 35 field isolates except for 2 isolates. RFLP analysis with MluI, HincII, SacII, HaeIII and MspI demonstrated that 35 field isolates were divided into 14 distinct codes and 34 isolates were distinguished from VR2332-derived modified live PRRSV vaccine, indicating the existence of genetic diversity in PRRSV field isolates in Japan. Only one strain 98-4A had an RFLP pattern identical to the vaccine strain. Nine out of the 35 field isolates (25.7%) had the RFLP code 1-3-2-1-1 and these patterns occurred throughout the examination period. This suggests that these isolates are the prevailing strain of PRRS in Chiba prefecture. RFLP with 5 enzymes demonstrated that various strains existed in the same year, and that there were different codes on the same farm according to the year. These observations indicate that there is a genetic variation among field isolates in very limited regions and some viruses possess the ability to cause their own genomic substitutions within a herd in a short time. PMID- 11767055 TI - Canine parentage testing based on microsatellite polymorphisms. AB - To establish an accurate method for parentage testing in dogs, microsatellite DNA repeat length polymorphisms were examined. We selected twenty microsatellite markers reported previously and examined their application for parentage testing in Beagles and Labrador Retrievers. Heterozygosity (He), Polymorphism Information Content (PIC), the probabilities of Paternity Exclusion (PE) and the combined PE were calculated from allelic frequencies of the markers. All markers amplified by polymerase chain reactions were polymorphic and many markers showed high He and PIC in the both breeds. The final combined PEs in Beagles and Labrador Retrievers were 0.999994 and 0.999920, respectively. The results suggest that the twenty markers can be applied for routine parentage testing in dogs. PMID- 11767056 TI - Prevalence of Chlamydophila abortus infection in domesticated ruminants in Taiwan. AB - This study is to (1) investigate the prevalence of Chlamydophila abortus infection in cows and goats in Taiwan, and (2) compare the genetic properties of Taiwanese isolates with abortion strains from other sources. Approximately 71% of aborted cows and 58% of aborted does had IgG against C. abortus in their sera. The seroprevalence rate in cows may be overestimated, because a certain degree of cross-reactivity with C. pecorum cannot be ruled out. Only 22.7% (from aborted cows) and 33.3% (from aborted dogs) of vaginal swabs that tested positive by polymerase chain reaction led to successful isolation of C. abortus by inoculation into chicken embryos, equivalent to 7.1% and 7.9% of isolation rates, respectively. The major outer membrane protein gene of 15 Taiwanese abortion isolates was compared with that of various strains by restriction fragment length polymorphism (RFLP) and nucleotide sequencing. Restriction enzyme CfoI was able to distinguish Taiwanese ruminant isolates, which have identical RFLP patterns, from C. felis (feline) and C. psittaci (avian) strains. Taiwanese isolates had 98.8-100% homology with known ruminant abortion strains and were phylogenetically closest to bovine LW508 strain. PMID- 11767057 TI - Effects of rearing conditions on the colonization of Salmonella enteritidis in the cecum of chicks. AB - Salmonella enteritidis is the cause of human salmonellosis associated with contaminated eggs. In this study, we artificially challenged S. enteritidis to chicks just after hatching, and the effects of breeding conditions on the intestinal carriage of S. enteritidis were examined. S. enteritidis was not directly detected from spleen, liver and blood, but were constantly isolated from the cecal contents throughout the experiment. When chicks were reared in the unsanitary conditions and in the high housing density, the numbers of S. enteritidis increased. The subsequent experiment was undertaken to examine whether the antibacterial additive in a feed would have any impact on S. enteritidis colonization in chicks. Some antibiotic effective on the growth promotion had an influence on S. enteritidis colonization. PMID- 11767058 TI - Survey of tick infestation and tick-borne ehrlichial infection of dogs in Ishigaki Island, Japan. AB - Twelve (54.5%) of 22 free-roaming dogs in Ishigaki Island had tick infestation identified as Rhipicephalus sanguineus. There were 121 ticks recovered and consisted of 28 females, 58 males, 22 nymphs and 3 larvae. Infection of dogs possibly with canine ehrlichial pathogens was examined by both indirect immunofluorescence assay and polymerase chain reaction (PCR). Two dogs of the 13 examined were sero-positive for the human granulocytic ehrlichia agent, and one of two dogs was PCR positive for Ehrlichia platys. This dog had platelet numbers slightly lower than normal value, however, no morulae were found within platelet on peripheral blood smear stained with Giemsa. PMID- 11767059 TI - Histoplasmosis in the lung of a race horse with yersiniosis. AB - A 4-year-old female thoroughbred race horse died of acute peritonitis caused by necrotizing granulomatous duodenitis. Yersinia enterocolitica was immunohistochemically demonstrated in macrophages in granulomas developed in the duodenum, lung, liver and abdominal lymph nodes. The yeast-like fungi were found in the cytoplasmic vacuoles of macrophages in the lung that infiltrated into the granulomas and surrounding alveoli with congestive edema. The yeast-like fungi were positively stained by Gomori-Grocott chromic acid methenamine silver stain and immuno-histochemically stained with anti-histoplasma antibody. In this case, it was considered that granulomas formed in the duodenum, lung, liver and abdominal lymph nodes were primarily caused by Yersinia enterocolitica due to idiopathic weakening of the immune system. Yeast-like fungi immunohistochemically identified as histoplasmas secondarily infected the lung. This is the first case regarded as equine histoplasmosis capsulati in Japan. PMID- 11767060 TI - Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix). AB - A 22-year-old female mandrill (Mandrillus sphinix) with continuously growing mass at the right mammary gland area was found dead, and a postmortem examination was performed. At necropsy, an elevated firm subcutaneous mass about 5 cm in diameter was present at the right mammary gland area. Axillary, mediastinal, and tracheobronchial lymph nodes were enlarged 2 to 4 times their normal sizes. Numerous metastatic foci 2 to 5 mm in diameter were scattered in the lung. Histologically, the tumor was diagnosed as mammary gland adenocarcinoma. Metastasis to the regional lymph nodes and lung was also confirmed. This is the first reported case of a mammary gland tumor in mandrill in Asia. PMID- 11767061 TI - Evaluation of diagnostic availability of continuous ANP assay and LA/AO ratio in left heart insufficient dogs. AB - Left atrial/aorta ratio (LA/AO) by echocardiography and the plasma level of atrial natriuretic peptide (ANP) were measured in 32 dogs with left heart insufficiency. There was a significant correlation between plasma ANP concentration and LA/AO (r=0.66, p<0.001). The authors obtained the result that the degree of expansion of the left atrial diameter seemed to have a close relationship with plasma ANP concentration. Plasma ANP concentration decreased when the clinical signs of the patients improved. However, the LA/AO ratio after treatment did not decrease. From these findings, we concluded that plasma ANP concentration has the possibility to become a significant index in the diagnosis and prognosis of heart disease in dogs. PMID- 11767063 TI - Ivermectin treatment of demodicosis in 56 hamsters. AB - Fifty-six hamsters with demodicosis were treated with daily oral administration of ivermectin (0.3 mg/kg). Thirty-three cases (58.9%) were cured and 6 cases (10.7%) had improved clinically but needed to continue treatment. Of 5 cases (8.9%) who relapsed within 3 months and were retreated with ivermectin, 4 were cured and 1 needed further treatment. Five cases (8.9%) had improved clinically but died within 3 months. Seven cases (12.5%) had not improved and died within 3 months. Overall 49 (87.5%) hamsters had improved clinically. No significant differences in prognosis of demodicosis were detected according to sex, breed, age and clinical features, but the prognosis of demodicosis in hamsters with concurrent disease was poor. PMID- 11767062 TI - Seasonal changes in serum total thyroxine, free thyroxine, and canine thyroid stimulating hormone in clinically healthy beagles in Hokkaido. AB - The purpose of this study was to evaluate seasonal influences on thyroid hormone levels of healthy outdoor dogs in Hokkaido. We surveyed serum basal total thyroxine (tT4), free thyroxine (fT4), and canine thyroid-stimulating hormone (cTSH) levels, and tT4 levels after administration of TSH for a year. Basal tT4 levels decreased in January, and increased in August and September. fT4 levels increased in January and November. No significant seasonal variation was found in cTSH. tT4 levels after administration of TSH in August and November increased. These results suggested that the thyroid gland may have been activated in November. We should take seasonal variation into consideration when thyroid function is tested. PMID- 11767064 TI - Apocrine adenocarcinoma in a golden hamster. AB - An apocrine adenocarcinoma was observed in the subcutis of the abdomen of golden hamster. Histologically, the tumor cells irregularly formed multiple layers of cysts and some detached cells were presented in the cystic space. PAS stain with alpha-amylase digestion revealed PAS-positive alpha-amylase-resistant granules in the cytoplasm. Immunohistochemically, cytokeratin was demonstrated in the tumor cells. By electron microscopy, the tumor cells had an oval nucleus with invagination, abundant cytoplasmic organelles and microvilli protruding into the intercellular spaces. PMID- 11767065 TI - A serodiagnostic ELISA using recombinant antigen of swine transmissible gastroenteritis virus nucleoprotein. AB - A serodiagnostic ELISA utilizing the recombinant nucleoprotein (rN protein) of transmissible gastroenteritis virus (TGEV) was developed, and evaluated by examining a panel of 141 virus neutralization (VN) positive and 101 negative sera. The rN protein-based ELISA (rnELISA) appeared to be highly sensitive and specific (98.6% and 98.0%, respectively) when it was compared to the VN test. The result was similar to that of an ELISA based on purified viral antigens with showing good correlation (R=0.829). No cross-reaction was detected with antisera against porcine epidemic diarrhea virus, hog cholera virus, type A rotavirus, pseudorabies virus and swine vesicular disease virus in this ELISA. The rnELISA can be an alternative for the diagnosis of TGE with a great advantage in antigen preparation. PMID- 11767066 TI - Evaluation of 13C-phenylalanine and 13C-tyrosine breath tests for the measurement of hepatocyte functional capacity in patients with liver cirrhosis. AB - Liver disease is associated with an abnormal elevation of the plasma concentrations of the aromatic amino acids phenylalanine and tyrosine. The liver is the main site of aromatic amino acid metabolism, particularly the hydroxylation of phenylalanine to tyrosine and further tyrosine degradation. In the present study, we have examined the usefulness of the L-[1-13C]phenylalanine breath test (13C-PheBT) and L-[13C]tyrosine breath test (13C-TyrBT) for the detection of hepatic damage in patients with liver cirrhosis. First, the time courses of 13CO2 excretion after the administration of L-[1-13C]phenylalanine and L-[1-13C]tyrosine were compared. The peak times (the time expressed in minutes at which 13CO2 excretion was maximal) were 20 min in both breath tests, but 13C TyrBT gave a higher peak than 13C-PheBT. Next, the parameters of 13C-PheBT and 13C-TyrBT were compared with biochemical liver function test values. These parameters were well correlated with several liver blood test values conventionally regarded as measures of hepatocyte functional reserve. Therefore, 13C-PheBT and 13C-TyrBT may be useful to assess the degree and progression of hepatic dysfunction. PMID- 11767067 TI - Measurement of the length of the a helical section of a peptide directly using atomic force microscopy. AB - Using atomic force microscopy (AFM), the length of the alpha-helix structure of poly-L-lysine was investigated by stretching the peptide directly, one molecule at a time. In the absence of urea, many rupturing points that seemed to be due to the breaking of some hydrogen bonds were observed in force-extension curves, while these points were never observed in the presence of 8 M urea. In the presence of 0.4 or 1.6 M urea, both force-extension curve types were observed. Total peptide elongation for each condition was calculated from force-extension curves reflecting the alpha-helix rupturing process. The experimental value of total elongation divided by the theoretical value of total alpha-helix elongation yields the alpha-helix content. This value was compatible with circular dichroism (CD) measurement results. This suggests that peptide conformation and content of the alpha-helix on a single molecule scale can be investigated by direct mechanical measurement using atomic force microscopy. PMID- 11767068 TI - Synthesis, characterization, DNA binding and cytotoxic studies of platinum(II) and palladium(II) complexes of the 2,2'-bipyridine and an anion of 1,1 cyclobutanedicarboxylic acid. AB - Two neutral complexes of formula [M(bpy)(cbdca)] [where M is palladium(II) (Pd(II)) or platinum(II) (Pt(II)), bpy is 2,2'-bipyridine and cbdca is anion of 1,1-cyclobutanedicarboxylic acid] have been synthesized. These water soluble complexes have been characterized by chemical analysis and conductivity measurements as well as 1H-NMR, ultraviolet-visible and infrared spectroscopy. In these complexes the ligand cbdca coordinates to Pt(II) or Pd(II) as bidentate with two oxygen atoms. They are nonelectrolyte in conductivity water. These complexes inhibit the growth of P388 lymphocytic leukemia cells and their targets are DNA. They invariably show ID50 values less than cisplatin. [Pt(bpy)(cbdca)] and [Pd(bpy)(cbdca)] have been interacted with calf thymus DNA and bind to DNA through coordinate covalent bond. In addition, the influence of binding of these complexes on the intensity of EtBr-DNA have been studied. They bind to DNA via a nonintercalating mode. PMID- 11767069 TI - Constituents of ophiuroidea. 1. Isolation and structure of three ganglioside molecular species from the brittle star Ophiocoma scolopendrina. AB - Three ganglioside molecular species, OSG-0 (1), OSG-1 (2), and OSG-2 (3) have been obtained from the polar lipid fraction of the chloroform/methanol extract of the brittle star Ophiocoma scolopendrina. The structures of these gangliosides have been determined on the basis of chemical and spectroscopic evidence as 1-O [(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1 O-[8-O-sulfo-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyll ceramide (2) and 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->8)-(N-acetyl- and N glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneous unsubstituted fatty acid, 2 hydroxy fatty acid and phytosphingosine units. Compounds 2 and 3 represent new ganglioside molecular species. PMID- 11767070 TI - Effects of dehydration temperatures on moisture absorption and dissolution behavior of theophylline. AB - Anhydrous theophylline was prepared by heating theophylline monohydrate at temperatures between 60 degrees C and 140 degrees C. The effects of dehydration temperatures on the moisture absorption and dissolution behavior of anhydrous theophylline were investigated in this study. The hydration rate of anhydrous theophylline at 95% relative humidity and 25 degrees C decreased with increasing dehydration temperatures. From the fitting analysis of solid-state reaction models, the hydration reaction was found to be governed by the phase boundary reaction model for samples prepared at lower dehydration temperatures (<100 degrees C) but the reaction obeyed the growth of nuclei reaction model when samples were dehydrated at higher temperatures. The dissolution rates of various anhydrous theophylline samples were measured by the rotating disk method. The calculated solubility of anhydrous theophylline prepared by heating was about 2.5 times higher than that of theophylline monohydrate. The phase transformation rate from the anhydrous form to the monohydrate during dissolution tests decreased with higher dehydration temperatures. It was found that the anhydrous theophylline prepared at different dehydration temperatures transformed to the monohydrate by way of different growth of hydrate nuclei mechanism. PMID- 11767071 TI - Solution properties and photonuclease activity of cationic bis-porphyrins linked with a series of aliphatic diamines. AB - The development of efficient photo-induced DNA cleavage agents has been of particular interest for biomedical applications such as cancer photodynamic therapy (PDT). Toward this objective, we synthesized a series of cationic bis porphyrins with various lengths of diamino alkyl linkage, N,N'-bis[4-[10,15,20 tris(1-methylpyridinium-4-yl)porphyrin-5-yl]benzoyl]oligomethylenediamine hexaiodide. They were expected to show more efficient photocleavage of DNA than unichromophore meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP), which is well known to cleave DNA effectively on illumination. The cationic bis-porphyrins were found to self-aggregate in aqueous solution, and the aggregation property was accounted for by the formation of an intermolecular dimer. Because conservative-type circular dichroism spectra of the bis-porphyrins were induced in the Soret region on binding to calf thymus DNA, we assigned their binding mode to outside self-stacking on the DNA surface. Their photonuclease activity using plasmid DNA decreased as the number of their linker hydrocarbons increased, and was well correlated with their tendency for dimerization. The inhibitory effect of azide anion, N3-, and the enhancement effect of D2O suggest that singlet oxygen was probably involved in the photocleavage of DNA. PMID- 11767072 TI - Redox reaction of artemisinin with ferrous and ferric ions in aqueous buffer. AB - Artemisinin, a sesquiterpene with endoperoxide bond, possesses potent antimalarial activity against the ring and late stage of chloroqine-resistant Plasmodium falciparum malaria both in vitro and in vivo. The mode of antimalarial activity of artemisinin is iron-dependent. The aim of this study was to investigate the reactions of artemisinin with ferrous and ferric ions in aqueous buffer. Artemisinin generated a cycle of iron oxidation and reduction. It oxidized ferrous and reduced ferric ions with similar rate of reaction (k=10+/ 0.5 M(-1) x s(-1) for ferrous and k=8.5+/-2.0 M(-1) x s(-1) for ferric ion). The major active product was dihydroartemisinin which exhibited antimalarial activity at least 3 times more potent than artemisinin. Dihydroartemisinin preferably binds to ferric ion, forming ferric-dihydroartemisinin complex. The re-oxidation of the complex gives artemisinin and ferric ion. This suggests that in aqueous buffer, the reaction of artemisinin with iron may give rise to the active reaction products, one of them being dihydroartemisinin, which is responsible for antimalarial activity. PMID- 11767073 TI - Functional modification of cytochrome c by peroxynitrite in an electron transfer reaction. AB - The redox reaction of cytochrome c after modification with peroxynitrite under physiological conditions was investigated. Cytochrome c was treated with a bolus of synthetic peroxynitrite at a sub-millimolar concentration, and then subjected to reduction by superoxide and oxidation by hydrogen peroxide. The ability for the membrane potential formation in the mitochondrial respiratory chain was also evaluated. After the treatment with peroxynitrite, the cytochrome c molecule was mono-nitrated mainly at a tyrosine residue, using liquid chromatography electrospray ionizing mass spectrometry (LC-ESI-MS) and HPLC. Although the redox capacity of cytochrome c was not affected by the peroxynitrite treatment, the oxidation of ferrocytochrome c to ferricytochrome c by hydrogen peroxide was accelerated. When cytochrome c was treated with peroxynitrite in the presence of 5-methoxytryptamine, an inhibitor for the tyrosine nitration by peroxynitrite, the acceleration of hydrogen peroxide-mediated oxidation was suppressed. It was also found that the formation of membrane potential in the rat liver mitochondria was suppressed when peroxynitrite-treated cytochrome c was used instead of the intact cytochrome c in vitro. From these results, we concluded that the peroxynitrite-treated cytochrome c was nitrated at a tyrosine residue and became more susceptible to oxidation by hydrogen peroxide, concomitantly losing the ability to transfer electrons in the mitochondrial respiratory chain. It is suggested that the peroxynitrite-induced modification of cytochrome c increases the susceptibility to non-physiological oxidants, and may cause dysfunction of mitochondria by suppressing of membrane potential. PMID- 11767074 TI - Two new 2'-oxygenated flavones from Andrographis elongata. AB - Two new 2'-oxygenated flavones, 5,2',6'-trihydroxy-7-methoxyflavone (3) and skullcapflavone I 2'-O-beta-D-(4"-E-cinnamyl) glucopyranoside (5), together with three known flavones, 7-O-methylwogonin (1), skullcapflavone I (2) and skullcapflavone I 2'-O-beta-D-glucopyranoside (4) were isolated from the whole plant of Andrographis elongata, and the structures were elucidated by FAB-MS and one- and two-dimensional (1D- and 2D)-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and rotating frame Overhauser enhancement spectroscopy (ROESY) experiments, and chemical studies. PMID- 11767075 TI - Medicinal foodstuffs. XXVIII. Inhibitors of nitric oxide production and new sesquiterpenes, zedoarofuran, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, from Zedoariae Rhizoma. AB - A new eudesmane-type sesquiterpene, zedoarofuran, and six new guaiane- or seco guaiane-type sesquiterpenes, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, were isolated from aqueous acetone extract of Zedoariae Rhizoma together with 36 known sesquiterpenes and two diarylheptanoids. Their stereostructures were elucidated on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages were examined and 16 sesquiterpenes including gajutsulactones A and B, and bis(4 hydroxycinnamoyl)methane were found to show inhibitory activity. PMID- 11767076 TI - New bitter-tasting hemiterpene glycosides from the Japanese fern Hymenophyllum barbatum. AB - Hymenosides G--J were newly isolated from the Japanese fern Hymenophyllum barbatum, in addition to hymenosides A--F. The structures of hymenosides were elucidated by extensive two-dimensional nuclear magnetic resonance and/or chemical evidence. The structures of those aglycones were divided into three types, 1,4-dihydroxy-2-hydroxymethyl-but-2-ene, 1,4-dihydroxy-2-methyl-but-2-ene, and 3-hydroxy-5-hexanolide. The sugar moieties were also established by chemical and spectroscopic methods, which were acylated by phenylacetic acid derivatives. These glycosides had a bitter or weakly pungent taste. PMID- 11767077 TI - Synthesis and nucleic acid-binding properties of water-soluble porphyrins appending platinum(II) complexes. AB - We synthesized two water-soluble porphyrins appending platinum(II) complexes [alpha,beta-(4a) and alpha,alpha-(4b) 5,15-bis(2-trans-[PtCl(NH3)2]N-2 aminoethylaminocarbonylphenyl) 2,3,7,8,12,13,17,18-octamethylporphyrin] and studied their reactions with a variety of nucleic acids [disodium adenosine-5' monophosphate (AMP), disodium guanosine-5'-monophosphate (GMP), disodium thymidine-5'-monophosphate (TMP), disodium cytidine-5'-monophosphate (CMP), synthetic polymer poly(dG)-poly(dC), poly(dA)-poly(dT)] by 1H-NMR, UV-vis and FAB MS spectroscopies. Based on the denaturation experiments of synthetic nucleic acid polymers, we conclude that the presence of the porphyrins (5.6 microM) does not cause significant changes in the melting temperature of poly(dA)-poly(dT) (28 microM) (deltaT=1 degrees C) and shows reannealing. On the other hand, gradual melting of poly(dG)-poly(dC) (28 microM) occurs at a low temperature (deltaT= -27 degrees C) in the presence of the porphyrins (5.6 microM), and the solutions do not show reannealing phenomena. The results of UV-vis and 1H-NMR experiments revealed that the porphyrins bind to guanine bases and that the porphyrins bind to GMP more strongly than to the other nucleotides. The binding modes between the porphyrins and synthetic nucleic acids are affected more by the coordination of the nucleobase [poly(dG)-poly(dC)] to the Pt(II) in the porphyrins than by Coulomb and hydrophobic interactions. PMID- 11767078 TI - Total synthesis of (S)-(+)-curcudiol, and (S)-(+)- and (R)-(-)-curcuphenol. AB - A highly enantioselective synthesis of the versatile chiral synthons possessing one stereogenic center, (S)- and (R)-4-aryl-5-hydroxy-(2E)-pentenoate (3) was achieved based on the enzymatic reaction of (+/-)-3 with commercially available lipases MY-30 or OF-360 from Candida rugosa. Application of (S)-3 and (R)-3 to the total syntheses of(S)-curcuphenol (1), (S)-curcudiol (2), and (R)-curcuphenol (1), respectively, is described. PMID- 11767079 TI - A new drug delivery system using plasma-irradiated pharmaceutical aids. VIII. Delayed-release of theophylline from double-compressed tablet composed of eudragit as wall material. AB - The rapid release from a double-compressed tablet containing theophylline as a core drug with the pH-dependent water-soluble polymers, Eudragit L100, S100 or L100-55 used as a wall material was suppressed by argon plasma-irradiation due to an effect of inter-segmental cross-link reactions on the decrease in the surface polymer solubility of outer layer. In addition, the rapid theophylline release from the double-compressed tablet of Eudragit L100-55 with a lower glass transition temperature (Tg) has converted into the delayed-release system under a set of plasma operational conditions due to an additional effect of plasma heat flux on softening of Eudragit L100-55 surface resulting in the formation of the film-like surface with a particle-particle interlinking of the outer layer. PMID- 11767080 TI - Synthesis and structure-activity relationships in a series of ethenesulfonamide derivatives, a novel class of endothelin receptor antagonists. AB - In the previous paper, we described a series of the 2-arylethenesulfonamide derivatives, a novel class of ETA-selective endothelin (ET) receptor antagonists, including the compounds 1a, b. Compound 1a showed excellent oral antagonistic activities and pharmacokinetic profiles, and the monopotassium salt of 1 (YM-598 monopotassium) is in clinical trials. In this paper, we wish to report the investigation of the further details of structure-activity relationships (SARs) of the 2-phenylethenesulfonamide region in 1a. It was found that methyl substitutions at the 2-, 4- and 6-positions of the phenyl group in 1a led to the discovery of the ET(A)/ET(B) mixed antagonist (6s) with an IC50 of 2.2 nM for the ET(A) receptor. We also found that introduction of an ethyl group to the 1 position of the ethenyl group in 1a gave the ET(A) selective antagonist (6u) with an oral endothelin antagonistic activity in rats. PMID- 11767081 TI - Development of a stereoselective practical synthetic route to indolmycin, a candidate anti-H. pylori agent. AB - A stereoselective practical synthetic route to indolmycin is described. The route is composed of the regioselective coupling of indolyl magnesium halide with a trans-epoxy ester, diastereoselective oxazolone ring formation with guanidine and amine exchange reaction with methylamine. In the coupling step, use of dichloromethane as co-solvent and conversion of the resulting hydroxy ester to the hydroxy acid for purification, make this process efficient and practical. The oxazolone ring is formed in good yield without epimerization at the C5 position by treatment with guanidine and potassium tert-butoxide in tert-butanol at room temperature. In the final step, the amino group is efficiently converted to the methylamino group in aqueous methylamine solution at 5 degrees C. After examination of the route with racemates, indolmycin was synthesized stereoselectively in 22% total yield from optically active trans-epoxy ester. This route was applied to the preparation of the metabolites of indolmycin. PMID- 11767082 TI - 1,6-Asymmetric induction during the conjugate addition of arylcopper reagents to a chiral sulfinyl-substituted pyrrolyl alpha,beta-unsaturated amide. AB - The asymmetric conjugate addition of arylcopper reagents derived from aryl Grignard reagents and copper(I) iodide to a chiral 1-[2-(p tolylsulfinyl)]pyrrolyl cinnamide proceeded smoothly to give (3R)-adducts with high diastereoselectivities (> or =92% de) in high yields. Conjugate additions either of the cinnamide with the alkyl Grignard reagent-copper(l) iodide combination or of the crotonamide derivative with aryl Grignard reagent-copper(l) iodide gave moderate to good diastereoselectivities. With these sulfinyl pyrrolyl alpha,beta-unsaturated amides, the chiral auxiliary was efficiently recovered without any loss of optical purity after asymmetric conjugate addition. PMID- 11767083 TI - A new drug delivery system using plasma-irradiated pharmaceutical aids. IX. Controlled-release of theophylline from double-compressed tablet composed of cellulose derivatives as wall material. AB - The rapid release from a double-compressed tablet containing theophylline with the water-soluble polymer, hydroxypropylmethylcellulose (HPMC) or hydroxypropylmethylcellulose phthalate (HPMCP), used as a wall material can be suppressed by argon plasma-irradiation and changed into the sustained-release system due to a decrease in solubility of the outer layer. It was shown that the release profiles can be varied so as to cause theophylline release at different rates, depending on the set of conditions chosen for tablet manufacture and for plasma operation. PMID- 11767084 TI - A practical preparation of methyl 2-methoxy-6-methylaminopyridine-3-carboxylate from 2,6-dichloro-3-trifluoromethylpyridine. AB - An effective and practical synthetic route to methyl 2-methoxy-6 methylaminopyridine-3-carboxylate (7), the key intermediate of 5-bromo-2-methoxy 6-methylaminopyridine-3-carboxylic acid (1), from 2,6-dichloro-3 trifluoromethylpyridine (12) was undertaken. Process improvements were highlighted by regioselectivity of 12 with a nitrogen nucleophile and conversion of the 3-trifluoromethyl group into the methoxycarbonyl group. The reaction of 12 with N-benzylmethylamine provided the 6-(N-benzyl-N-methyl)aminopyridine 26a and the regioisomer 26b in >98:<2 ratio in a quantitative yield. Treatment of 2 methoxy-6-methylamino-3-trifluoropyridine (14a) with a large excess of sodium methoxide followed by acid hydrolysis gave the pyridine-3-carboxylic ester 7 in an excellent yield. The potential application of this reaction is also described. PMID- 11767085 TI - 3,7-Dimethylguanine, a new purine from a Philippine sponge Zyzzya fuliginosa. AB - A new purine 3,7-dimethylguanine (1) has been isolated from the marine sponge Zyzzya fuliginosa, along with the known metabolites, makaluvamines A, C, K (2- 4), 4-hydroxyphenylacetic acid (5), methyl ester of 4-hydroxyphenylacetic acid (6), 4-hydroxyphenethyl alcohol (7), L-phenylalanine (8) and L-tryptophan (9). The structure of 3,7-dimethylguanine (1) was elucidated by analysis of 1D and 2D (one- and two-dimensional) NMR [HMQC (heteronuclear multiple quantum coherence), gHMBC (heteronuclear multiple bond connectivity), 1H-15N gHMBC] data, mass spectroscopy data, and by comparison with 3,7-dimethylisoguanine (10). PMID- 11767086 TI - 3-Benzamido, ureido and thioureidoimidazo[1,2-a]pyridine derivatives as potential antiviral agents. AB - This work reports the synthesis and the antiviral activities of 3-benzamido, 3 phenylureido and 3-phenylthioureido derivatives in the imidazo[1,2-a]pyridine series. The structure was proven by NMR spectroscopy. The synthesized compounds were evaluated against a large number of viruses. The 3-phenylthioureido derivative 7 showed moderate activity against human cytomegalovirus (HCMV) in vitro. The crystallographic data for 8 are also reported and explain the absence of activity against human immunodeficiency virus (HIV). PMID- 11767087 TI - Allixin induction and accumulation by light irradiation. AB - Allixin, a phytoalexin isolated from garlic, was induced by irradiating fresh garlic cloves with sunlight or UV light. Induced allixin was analyzed by HPLC, and the accumulated amounts of allixin were 3.1-6.3 microg/g under experimental conditions. PMID- 11767088 TI - Reactivity of 2-methylene-1,3-dicarbonyl compounds. 1,3-dipolar cycloaddition reaction with ethyl diazoacetate. AB - The reaction of 2-methylene-1,3-dicarbonyl compounds (1) with ethyl diazoacetate gave 4,5-dihydro-1H-pyrazole derivatives (2), which were stable for several months at room temperature in good yields. PMID- 11767089 TI - The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium. AB - A human intestinal bacterium, Eubacterium (E.) sp. strain SDG-2, was tested for its ability to metabolize various (3R)- and (3S)-flavan-3-ols and their 3-O gallates. This bacterium cleaved the C-ring of (3R)- and (3S)-flavan-3-ols to give 1,3-diphenylpropan-2-ol derivatives, but not their 3-O-gallates. Furthermore, E. sp. strain SDG-2 had the ability of p-dehydroxylation in the B ring of (3R)-flavan-3-ols, such as (-)-catechin, (-)-epicatechin, (-) gallocatechin and (-)-epigallocatechin, but not of (3S)-flavan-3-ols, such as (+) catechin and (+)-epicatechin. PMID- 11767090 TI - Synthesis of 2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid, an important intermediate of rosmarinic acid biosynthesis. AB - A simple method to synthesize (+/-)-2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid (1), a key intermediate in rosmarinic acid biosynthesis in higher plant cells, was established by condensation of protected 4-coumaric acid and (+/-)-3 (4-hydroxyphenyl)lactic acid followed by deprotection. A stable supply of 1 thus attained will lead to biochemical and molecular biological characterization of later steps of rosmarinic acid biosynthesis. PMID- 11767091 TI - Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758. AB - Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R 102557 were examined. Variation of the length of the chain between the dioxane ring and the phenyl ring revealed that the linkage with two double bonds is the most preferable. When a cyano group was introduced to the C4 position on the benzene ring, MICs improved further. A fluorine atom was introduced to obtain CS 758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4-methylbenzonitrile using the Horner Wadsworth-Emmons reaction. PMID- 11767092 TI - Effects of counter cations of base catalysts on nitrosation mechanisms. AB - Reaction of 2-butanone (1) with tert-butyl nitrite (tert-BuONO) was performed using base catalysts (RO-M+: R=CH3, C2H5; M+=Li+, Na+, K+) in alcohols (CH3OH or C2H5OH). In this report, the effects of M+ of RO-M+ on the nitrosation mechanisms were investigated. The yield of E-hydroxyimino compound (5E) increases much better in the reaction using Na+ or K+ as M+ compared with that using Li+. It is also observed that the yield of 5E increases by addition of crown ether as a cation-capturing agent. The experimental results suggested that under the conditions lowering the effects of M+ of RO-M+ on the nitrosation mechanisms, because the reactivity of naked enolate of I increases and the reaction in the C N bond formation process tends to proceed via open-chain transition state without M+, the yield of 5E tends to increase. PMID- 11767093 TI - An approach to a chiral cycloalkanone-mediated asymmetric epoxidation of stilbene with oxone. AB - Chiral and C2-symmetric seven-membered cycloalkanones 2--6 bearing 1,2 diphenylethane-1,2-diamine and cyclohexane-1,2-diamine backbones were synthesized and evaluated their asymmetry inductive behaviours in an asymmetric epoxidation of stilbene with oxone. Although the reaction of the ketones 2 and 3 of a 1,2 diphenylethane-1,2-diamine backbone gave stilbene oxide in trace to 31% yield, those of the ketones 4-6 of a cyclohexane-1,2-diamine backbone gave the epoxide in satisfactorily high yield up to 98%. It is noteworthy that both reactions with use of stoichiometric and substoichiometric amounts of a ketone 4 gave the epoxide in the essentially same enantioselectivity, 17 and 18%. Eleven-membered cyclic ketones 7 and 8 bearing a binaphthalene backbone were also synthesized and examined their behaviours, while the enantioselectivity turned out to be marginal. PMID- 11767094 TI - Regioselective nucleophilic addition of methoxybenzene derivatives to the beta carbon of p-benzoquinone mono O,S-acetal. AB - Regioselective nucleophilic addition of electron rich aromatics to the beta position of acetal carbon of p-benzoquinone mono O,S-acetal was achieved by modifying the acetal moiety. PMID- 11767095 TI - Synthesis and antibacterial activity of new 1beta-methylcarbapenems having the potential for intramolecular nonbonded S...O interactions. AB - Mercaptoacetyliminothiadiazoline derivatives (19, 20) useful for the pendant moiety of 1beta-methylcarbapenem antibiotics were efficiently synthesized. Acetyl derivative (18) of 20 was submitted to X-ray analysis, and a significant nonbonded S...O close contact was recognized in the crystallographic structure. New 1beta-methylcarbapenems (5, 6) were synthesized by exploiting 19 and 20, and exhibited considerable antibacterial activities in vitro. PMID- 11767096 TI - Total synthesis of capsanthin using lewis acid-promoted regio- and stereoselective rearrangement of tetrasubstituted epoxide. AB - The synthesis of capsanthin 1 was accomplished via the C15-cyclopentyl ketone 13 prepared by Lewis acid-promoted regio- and stereoselective rearrangement of the epoxide 12. PMID- 11767097 TI - Ardisiphenols A-C, novel antioxidants from the fruits of Ardisia colorata. AB - Novel alk(en)ylphenols, named ardisiphenols A--C (1--3) were isolated from the fruits of Ardisia colorata, together with known alk(en)ylresorcinols (4--6). Their structures were determined by the NMR and MS/MS analyses. All compounds showed scavenging activities towards 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and cytotoxicities against murine breast cancer cell line, FM3A. PMID- 11767098 TI - Transferrin is not involved in the entry of 67Ga into hepatocytes from regenerating liver of partially hepatectomized rats. AB - Ever since the first observation of 67Ga accumulation in tumors and inflammatory lesions, 67Ga has been used to detect various tumors and inflammations. The aims of this study were to clarify whether or not transferrin is involved in the uptake of 67Ga by the regenerating liver after partial hepatectomy. The uptake of 67Ga by the liver of rats reached a maximum 2 d after partial hepatectomy. In order to inhibit the binding of 67Ga to transferrin in the blood, FeCl3 was administered 5 min before the injection of 67Ga. The administration of FeCl3 decreased the uptake of 67Ga by the liver of the partially hepatectomized rats, suggesting that transferrin is involved in the uptake by the liver. However, 67Ga was taken up only slightly by hepatocytes obtained from the liver of these rats. We conclude that transferrin is involved in the uptake of 67Ga by the liver tissue of partially hepatectomized rats but is not involved in its entry into the hepatocytes. Only a slight amount of gallium-67 enters the hepatocytes, and may accumulate primarily in the extracellular matrix of the liver tissue of these rats. PMID- 11767099 TI - Difference in subcellular distribution between 45- and 37-kDa mevalonate pyrophosphate decarboxylase in rat liver. AB - We previously reported that the CP diet (a diet containing 5% cholestyramine and 0.1% pravastatin)-induced new species of 37-kDa mevalonate pyrophosphate decarboxylase (MPD) was characteristically and immunologically very similar to the well-known 45-kDa MPD. In the present study, we found a difference in subcellular distribution between 45- and 37-kDa MPD by cell fractionation and immunoblot analysis. The cytosol fraction contained 45- and 37-kDa MPD. Peroxisomal fraction contained a small amount of 45-kDa MPD, but not 37-kDa MPD. Also, 45-kDa MPD in peroxisome is localized in the matrix. From these data, the difference in subcellular distribution between 45- and 37-kDa MPD may be due to differences in the physiological role of cholesterol biosynthesis in rat liver. PMID- 11767100 TI - Characterization of nuclear factors that bind to the human thymidylate synthase gene in HL-60 cells differentiated by all-trans retinoic acid treatment. AB - HL-60 cells differentiate into granulocyte-like cells by all-trans retinoic acid (ATRA) treatment, and the cellular proliferation is markedly reduced during the differentiation. To elucidate the molecular mechanisms of the growth arrest during the cellular differentiation, we examined the regulated expression of the thymidylate synthase (TS) gene. Northern blot analysis revealed that the expression of the TS gene was almost suppressed in the differentiated HL-60 cells. The change in the levels of nuclear factors, NF-TS2 and NF-TS3, that bind to the 5'-terminal regulatory region of the human TS gene was examined during the differentiation of the HL-60 cells. The amount of NF-TS2 did not change significantly during the differentiation, whereas that of NF-TS3 clearly increased as the cells differentiated. We previously reported that NF-TS2 and NF TS3 bind to the sequence around the initiation codon ATG of the human TS gene. Further analyses revealed that the DNA sequences of NF-TS2 and NF-TS3 are very similar, and the first and second positions of the ATG triplet codon are important for the formation of rigid DNA-protein complexes. The present findings concerning the binding site and changes during the differentiation induced by ATRA treatment are very similar to those previously reported on the differentiation induced by 1,25-dihydroxyvitamin D3 treatment. These findings suggest that NF-TS3 is involved in regulating the expression of the human TS gene during the differentiation of HL-60 cells, regardless of the terminal cell type: macrophage-like cells or granulocyte-like cells. PMID- 11767101 TI - Amino acid sequence of a trypsin inhibitor from a Spirometra (Spirometra erinaceieuropaei). AB - A trypsin inhibitor that is highly homologous with bovine pancreatic trypsin inhibitor (BPTI) was co-purified along with RNase from Spirometra (Spirometra erinaceieuropaei). The amino acid sequence of this inhibitor (SETI) and the nucleotide sequence of the cDNA encoding this protein were determined by protein chemistry and gene technology. SETI contains 68 amino acid residues and has a molecular mass of 7,798 Da. SETI has 31 amino acid residues that are identical with BPTI's sequence, including 6 half-cystine and 5 aromatic amino acid residues. The active site Lys residue in BPTI is replaced by an Arg residue in SETI. SETI is an effective inhibitor of trypsin and moderately inhibits a chymotrypsin, but less inhibits elastase or subtilisin. SETI was expressed by E. coli containing a PelB vector carrying the SETI encoding cDNA; an expression yield of 0.68 mg/l was obtained. The phylogenetic relationship of SETI and the other BPTI-like trypsin inhibitors was analyzed using most likelihood inference methods. PMID- 11767102 TI - Synthesis, purification and surface activities of the human pulmonary surfactant protein-C (SP-C) analogue, SP-CL16 (6-28). AB - We previously reported that a human analogue of pulmonary surfactant protein-C (SP-C), SP-CL16 (6-28), with 23 residues (Fig. 1) was the most active analogue in a reconstituted lipid mixture and had the shortest chain among the poly-leucine analogues examined. In the present study, we examined a new method of preparing this analogue, that is, stepwise solid-phase synthesis employing the Fmoc method followed by centrifugal partition chromatography (CPC) using an n hexane/CH3OH/H2O/trifluoroacetic acid (TFA) (1000: 1000:1:2, v/v) solvent system according to the descending method. The synthetic peptides were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry in search of activity to improve the in vitro surface activity of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, egg phosphatidylglycerol and palmitic acid (75:25:10, w/w) in a Langmuir-Wilhelmy surface balance. SP-CL16 (6-28) seemed comparable in surface activity with Surfacten (Surfactant-TA), a modified surfactant preparation which has been used for the treatment of respiratory distress syndrome. PMID- 11767103 TI - Enzymatic properties of sialic acid binding lectin from Rana catesbeiana modified with a water-soluble carbodiimide in the presence of various nucleophiles. AB - The anti-tumor activity of sialic acid binding lectin from Rana catesbeiana (cSBL) was increased by chemical modification with a water-soluble carbodiimide (EDC) in the presence of nucleophiles such as ethylenediamine and glycine methylester. Investigations on ribonuclease (RNase) activities of the modified cSBLs were conducted to elucidate the fundamental mechanisms underlying enhancement of the anti-tumor activity conferred by these modifications. The following three characteristics were observed with modification. (i) RNase activity of the modified cSBL was enhanced towards double stranded RNA and RNA oligo dA hybrids. The activity increase was observed even under physiologic ionic strength conditions; (ii) RNase activity of the modified cSBL towards single stranded RNA and poly U decreased, while the activity towards poly C was unaffected; (iii) the base preference of the B2 base recognition site of modified cSBL decreased for guanine. On the contrary, the preference for cytosine and adenine increased. This result may explain why the RNase activity towards poly C was not affected by EDC-modification as mentioned above. PMID- 11767104 TI - Tolerance to nitroglycerin induced by isosorbide-5-mononitrate infusion in vivo. AB - We examined the development of tolerance to nitroglycerin (glyceryl trinitrate; GTN) in the rat when isosorbide-5-mononitrate (ISMN) or GTN was continuously infused. Under pentobarbital anesthesia (60 mg/kg, i.p.), mean arterial blood pressure was measured via the left common carotid artery. Bolus injection of ISMN (0.25-250 mg/kg) and GTN (0.25 microg/kg-2.5 mg/kg) was made into the right external jugular vein. ISMN (2.5 mg/h/rat for 7 d), GTN (1.3 microg/h/rat for 7 d), or GTN (0.2 mg/h/rat for 3 d) was infused continuously using an osmotic pump embedded subcutaneously. Bolus injection of ISMN and GTN decreased arterial blood pressure in a dose-dependent manner. The hypotensive effect of ISMN was 2000 times less potent than that of GTN. The GTN-induced hypotensive effect was not affected after continuous infusion of ISMN, whereas it was attenuated after continuous infusion of GTN at either dose. Chronic treatment with ISMN does not induce GTN tolerance as easily as treatment with GTN. PMID- 11767106 TI - Polychlorinated biphenyls activate caspase-3-like death protease in vitro but not in vivo. AB - We prove here that serum albumin inhibits apoptosis induced by polychlorinated biphenyls (PCBs), confirming that serum albumin binds to PCB, and that the albumin-PCB complexes inhibit apoptosis in HL-60 cells. We found that PCB (50 microM) increased the activity of caspase-3-like protease when HL-60 cells, as well as splenocytes, were cultured in "serum-free medium." Benzyloxycarbonyl-Val Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited apoptosis in cells cultured in the serum-free medium containing 50 microM PCB. To elucidate whether or not PCBs induce apoptosis in vivo, we examined apoptosis of splenocytes by administering PCB to ICR mice (100, 500, 1000 mg x kg(-1) x d(-1)) for 5 d and characterizing splenocytes. Interestingly, splenocytes treated with PCB did not show any changes characteristic of apoptosis. These results demonstrate that PCB activates the caspase-3-like death protease in vitro in serum-free medium, but does not induce apoptosis of splenocytes in vivo, suggesting that blood serum may mask the apoptosis induced by PCB. PMID- 11767105 TI - Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing. AB - Extracts from the leaves of Chromolaena odorata have been shown to be beneficial for treatment of wounds. The crude ethanol extract of the plant had been demonstrated to be a powerful antioxidant to protect fibroblasts and keratinocytes in vitro. In this study, the most active compounds were fractionated and identified from the crude extract using liquid chromatography coupled with UV spectroscopy and mass spectrometry. The antioxidant effects of purified fractions on cultured fibroblasts and keratinocytes were investigated using colorimetric and lactate hydrogenase release assay. The results showed that the phenolic acids present (protocatechuic, p-hydroxybenzoic, p-coumaric, ferulic and vanillic acids) and complex mixtures of lipophilic flavonoid aglycones (flavanones, flavonols, flavones and chalcones) were major and powerful antioxidants to protect cultured skin cells against oxidative damage. In conclusion, the extract from C odorata contains a mixture of powerful antioxidant compounds that may be one of potential mechanism contributing to enhanced wound healing. PMID- 11767107 TI - Hair analysis for pharmaceutical drugs. II. Effective extraction and determination of sildenafil (Viagra) and its N-desmethyl metabolite in rat and human hair by GC-MS. AB - In order to study the incorporation of sildenafil (SDF) and its N-demethylated metabolite (norSDF) into hair, animal model experiments were carried out. After shaving the back hair, SDF was dosed to two sets of three male dark-agouti pigmented rats (5 weeks old) per each group at 25 mg/kg once a day for 5 successive days with intraperitoneal (i.p.) (set1) and oral administration (set2). The regrown back hair was collected 14 d after the first administration. Three typical extraction methods, using methanol-5 M hydrochloric acid, methanol trifluoroacetic acid and 1 M sodium hydroxide, were evaluated using the rat hair samples containing SDF and norSDF. Methanol-5 M hydrochloric acid was the best extraction method in terms of high efficiency and reproducibility. The extract was purified using Bond Elut Certify columns and was derivatized with trimethylsilylimidazole: N,O-bis(trimethylsilyltrifluoroacetamide): trimethylchlorosilane (3: 3: 2) at 90 degrees C for 30 min. The trimethylsilylated products were analyzed by GC-MS using selected ion monitoring. SDF and norSDF were simultaneously detected in the rat hair. The hair concentrations were 4.9-6.3 (av. 5.8) ng/mg and 15.6-20.3 (av. 17.6) ng/mg for SDF and norSDF, respectively, with i.p. administration, and 2.6-4.1 (av. 3.6) ng/mg and 8.1-10.4 (av. 9.1) ng/mg with oral administration. The hair concentrations of norSDF were about three times higher than those of SDF, and the ratios of both compounds showed no significant difference between i.p. and oral administrations. This method was applied to the scalp hair of two patients who orally took SDF at regular intervals for the treatment of penile erectile dysfunction. The hair concentrations of SDF and norSDF in the two patients were 19.8 and 55.9 ng/mg, and 1.7 and 5.6 ng/mg, respectively. PMID- 11767108 TI - Molecular analysis of medicinally-used Chinese and Japanese Curcuma based on 18S rRNA gene and trnK gene sequences. AB - Curcuma drugs have been used discriminatingly for invigorating blood circulation, promoting digestion, and as a cholagogic in China. However, there is confusion about the drug's botanical origins and clinical uses because of morphological similarity of Curcuma plants and drugs. In order to develop an ultimate identification, molecular analysis based on 18S rRNA gene and trnK gene sequences were performed on 6 Curcuma species used medicinally in China and Japan. The 18S rRNA gene sequences were found to be of 1810 bps in length. In comparison with the common sequence of C. longa, C. phaeocaulis, C. wenyujin and C. aromatica, that of C. kwangsiensis had one base substitution, and the same base difference was observed between the Chinese and the Japanese populations of C. zedoaria. The trnK gene sequences were found to span 2698-2705 bps. There were base substitutions, small deletions or insertions at some sites between the trnK coding region and matK region among each species. Based on the base substitutions, C. zedoaria and C. kwangsiensis specimens were divided into two groups, respectively. An identical sequence was detected in C. phaeocaulis and in the Chinese population of C. zedoaria, as well as in the Japanese population of C. zedoaria and in one group of C. kwangsiensis with a purple-colored band in leaves. New taxonomic information to be used for authenticating Curcuma drugs was obtained. PMID- 11767109 TI - The influence of commonly prescribed synthetic drugs for peptic ulcer on the pharmacokinetic fate of glycyrrhizin from Shaoyao-Gancao-tang. AB - The influence of synthetic drugs prescribed for peptic ulcer on the pharmacokinetic fate of glycyrrhizin (GL) from Shaoyao-Gancao-tang (SGT, a traditional Chinese formulation, Shakuyaku-Kanzo-to in Japanese) was investigated in rats. Co-administration of histamine H2-receptor antagonist (cimetidine) and anticholinergic drug (scopolamine butyl bromide) with SGT didn't influence the area under the plasma concentration-time curves (AUC) of glycyrrhetic acid (GA), an active metabolite derived from GL in SGT. The AUC of GA from SGT were significantly reduced by co-administration of synthetic drugs commonly used for peptic ulcer in a triple therapy (OAM), a combination of a proton pump inhibitor (omeprazole) and two antibiotics (amoxicillin and metronidazole). We found that the reduction of AUC in OAM treatment was due to the antibacterial effect of amoxicillin and metronidazole on intestinal bacteria in rat which lead to the decrease of GL-hydrolysis activity. The present study suggests that it may not be a proper way to use triple therapy containing antibiotics simultaneously with SGT for healing of chronic ulcers. PMID- 11767110 TI - Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H). AB - Continuous oral administration of the acidic polysaccharide (TAP) solution (0.5 g/l) and the TAP-H (degradation products of TAP) solution (1.5 g/l) instead of water for 10 weeks were found to depress plasma glucose increases in diabetes using genetically non-insulin-dependent diabetic model (KK-Ay) mice. TAP and TAP H significantly lowered levels of insulin, total-cholesterol and triglyceride in the blood of the mice. In excretion to feces, TAP and TAP-H significantly increased the total bile acid, while the cholesterol content of both groups was less than that of the control. Furthermore, TAP and TAP-H significantly decreased the plasma lipoperoxide level. The study shows that TAP and TAP-H have an antidiabetic effect on diabetes model mice. PMID- 11767111 TI - Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter. AB - The effects of 4-hydroxyantipyrine (4-OH), a major metabolite of antipyrine and its sulfate, 4-hydroxyantipyrine O-sulfate (4-S), on the pharmacokinetics of citicoline and thiopental sodium were investigated in rats. The concomitant use of 4-OH increased significantly the tissue-to-plasma concentration ratio (Kp) of citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart, while 4-S did not affect them. The permeability clearance of blood-brain barrier (BBB) (Kin) and the total distribution volume (Vdbr) of citicoline were not affected by either 4-OH or 4-S. However, those of thiopental sodium were significantly increased by not only 4-OH but also by 4-S. On the other hand, the plasma concentration of antipyrine was significantly decreased by the intravenous bolus coadministration of N-acetyl-p-aminophenyl O-sulfate (APAPS) at steady-state plasma concentration of antipyrine. A similar reduction was not observed with the intravenous coadministration of acetaminophen (APAP). The Kp value of antipyrine was significantly increased in the brain by the coadministration of APAPS, but was not affected by APAP. The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters. PMID- 11767112 TI - Spray-dried powders as nasal absorption enhancers of cyanocobalamin. AB - The aim of this work is to describe and characterize a new spray-drying procedure for the production of nasal powders as an alternative to the conventional freeze drying method. Cyanocobalamin was chosen as the active ingredient and loaded into five different nonsoluble vehicles with high water absorption ability. Then these hydrated particles were suspended in methylene chloride and spray-dried. Particle size, morphology, true, bulk and tapped density, percentage of compressibility, moisture content, water intake, and drug diffusion were studied and significant differences were obtained depending on the nature of the vehicle. The drying method, either the new spray- or the conventional freeze-drying, was less important. Interestingly, an inverse correlation was found between water uptake and drug diffusion. Microcrystalline cellulose, dextran microspheres, and crospovidone were chosen for an in vivo bioavailability study in rabbits. Three other nasal reference formulations and an intravenous solution were also administered. The spray-dried powders showed higher bioavailability than the three nasal reference formulations. The highest absorption enhancement was observed with cellulose microcrystalline powders, which provided a 25% mean absolute bioavailability, followed by crospovidone and dextran microspheres formulations with mean bioavailability values of 14% and 7%, respectively. In conclusion, the new spray-drying method is useful for the production of cyanocobalamin nasal powders. PMID- 11767113 TI - Mevalonate pyrophosphate decarboxylase in stroke-prone spontaneously hypertensive rat is reduced from the age of two weeks. AB - We carried out a comparison of tissue distribution of mevalonate pyrophosphate decarboxylase (MPD) between normotensive Wistar Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rat (SHRSP) using Western blotting. However, there was no difference in tissue distribution of MPD between WKY and SHRSP, expect in brain and liver. We then compared the MPD between WKY and SHRSP liver at several weeks of age. We found that MPD in the liver as well as brain of SHRSP was significantly reduced from two weeks of age. This data is useful to identify or understand the mechanism underlying the reduced amount of MPD in SHRSP. PMID- 11767114 TI - Trichorzin HA V, a member of the peptaibol family, stimulates intracellular cAMP formation in cells expressing the calcitonin receptor. AB - By a cell-based screening of an in-house natural product library, trichorzin HA V, belonging to a peptaibol family, was isolated from a strain of fungus Trichoderma as a calcitonin (CT) agonist. Like CT, trichorzin HA V elevated cAMP levels in T47D cells which endogenously express the human CT receptor. It also stimulated cAMP formation in cells expressing recombinant human CT receptor, but not in those that do not express the receptor, suggesting that it selectively interacts with the CT receptor. In contrast to trichorzin HA V, alamethicin, another well-characterized peptaibol, showed no cAMP-elevating activity at all. These results suggest that, although there was little amino acid sequence similarity between trichorzin HA V and CT, the biological activity of trichorzin HA V can mimic that of CT, acting via the CT receptor. PMID- 11767115 TI - Evaluation of ppk-specified polyphosphate as a mercury remedial tool. AB - To evaluate the utility of polyphosphate kinase gene (ppk)-specified polyphosphate in mercury remediation, a fusion plasmid, pMK27, with ppk from Klebsiella aerogenes and mercury transport genes, merT and merP, from Pseudomonas K-62, was constructed. The transcription and translation of ppk, merT and merP were found to be mercury-inducible. The ppk-specified polyphosphate was identified in cells preinduced by Hg2+, but not in cells without mercury induction, suggesting that the synthesis of polyphosphate is regulated by merR. The hypersensitive phenotype to Hg2+, shown by bacteria with pMRD141, which contains merT and merP, was almost completely restored to its original levels when the ppk was introduced into the plasmid, suggesting that the Hg2+-toxicity was reduced by the polyphosphate, probably via chelation formation. Bacteria with pMK27 accumulated approximately 6-fold more mercury than the bacteria with cloning vector, pUC119. These results clearly demonstrate that the polyphosphate is capable of retaining mercury in the cells without taxing the cells. Based on the results obtained in the present study, the fusion plasmid pMK27 may serve as a strategy for mercury remediation. PMID- 11767116 TI - Non-synonymous single nucleotide alterations found in the CYP2C8 gene result in reduced in vitro paclitaxel metabolism. AB - By sequencing genomic DNA from 73 established cell lines derived from Japanese individuals, we detected 9 single nucleotide polymorphisms (SNPs) in the CYP2C8 gene. Of them, 3 exonic SNPs resulted in amino acid alterations (g416a, R139K; a1196g, K399R; c1210g, P404A). The first two alterations were detected concurrently in one cell line and thought to be the same as CYP2C8*3. To examine the effects of these amino acid alterations on CYP2C8 function, wild-type and four types of variant CYP2C8 cDNA constructs (R139K, K399R, R139K/K399R and P404A) were transfected into Hep G2 cells and their paclitaxel 6a-hydroxylase activities were determined in vitro. Km values were not significantly different from that of the wild-type in any of the variants studied. The variant R139K/K399R showed reduced values for Vmax and clearance (Vmax/Km) similar to those of its single variant, R139K. The variant P404A also showed a significantly lowered clearance due to reduced level of protein expression. These results suggest that not only the double variant (R139K/K399R, CYP2C8*3) but also our novel variant P404A in the CYP2C8 gene are less efficient in paclitaxel metabolism. PMID- 11767117 TI - The 5-HT2C/2B receptor agonist m-chlorophenylpiperazine (mCPP) inhibits 2-deoxy-D glucose (2-DG)-induced hyperphagia in rats. AB - Effects of the 5-HT2C2/2B receptor agonist m-chlorophenylpiperazine (mCPP) on hyperphagia elicited by 2-deoxy-D-glucose (2-DG) were investigated in rats. mCPP apparently reduced 2-DG-induced hyperphagia. Suppressive effects of mCPP on hyperphagia induced by 2-DG were inhibited by the 5-HT2A/2B/2C receptor antagonist, ritanserin, although the 5-HT2, receptor antagonist ketanserin was without effect. Thus, inhibitory effects of mCPP on 2-DG-induced hyperphagia are mediated by the 5-HT2C/2B receptor. Our results demonstrate that mCPP can inhibit the bulimia model, 2-DG-induced hyperphagia. PMID- 11767118 TI - Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice. AB - Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C. A. MEYER and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations > or = 2 microm. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals. PMID- 11767119 TI - Effect of polyphenols on calcium content and alkaline phosphatase activity in rat femoral tissues in vitro. AB - The effect of various polyphenols on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues of young rats in vitro was investigated. Bone tissues were cultured for 24 h in serum-free Dulbecco's modified Eagle's medium containing either vehicle or various polyphenols (10(-7) - 10(-4) M). The presence of genistein (10(-6) - 10(-4) M) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. Resveratrol (10(-4) m) decreased metaphyseal calcium content significantly, and it (10(-6) - 10(-4) M) had a significant inhibitory effect on diaphyseal enzyme activity. Epigallocatechin gallate (EGCg; 10(-4) M) significantly inhibited alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. EGCg (10(-7) - 10(-4) M) had no effect on bone calcium content. Meanwhile, glycitein, quercetin, or catechin in the range of 10(-7) to 10(-4) ml did not have an effect on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and metaphyseal tissues. The present study suggests that a phytoestrogen genistein has a unique anabolic effect on bone calcification in vitro. PMID- 11767120 TI - Anti-tumor-promoting activity of the diterpene from Excoecaria agallocha. II. AB - Eight new diterpenoids (1-8) have been isolated from the wood of Excoecaria agallocha (Euphorbiaceae) and their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) in Raji cells were examined to search for potent anti-tumor-promoters from natural resources. Of these compounds, the secolabdane-type diterpenoid, compound 7 exhibited a remarkable inhibitory effect on EBV-EA induction, and a significant anti-tumor-promoting effect in the mouse two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene and 12-O tetradecanovl-phorbol-13-acetate. PMID- 11767121 TI - Antiproliferative constituents in the plant 8. Seeds of Rhynchosia volubilis. AB - The MeOH extract of the seeds of Rhynchosia volubilis (Leguminosae) showed antiproliferative activity against human gastric adenocarcinoma [MK-1, 50% growth inhibition (GI50): 25 microg/ml], human uterus carcinoma (HeLa, GI50: 30 microg/ml), and murine melanoma (B16F10, GI50: 8 microg/ml) cells. Bioactivity guided fractionation resulted in the isolation of gallic acid methylester (1), gallic acid (2), 7-O-galloylcatechin (3), 1,6-di-O-galloylglucose (4), 1-O galloylglucose (5), and trigalloylgallic acid (6), and their antiproliferative activity was estimated. All showed much stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Compound 2 and its tetramer (6) with a free carboxyl group showed higher activity than those which did not have a free carboxyl group. In relation to the gallic acid tetramer (6), two gallic acid dimers (ellagic acid and dehydrodigallic acid) and trimers (tergallic acid dilactone and flavogallonic acid dilactone) were tested for their activity, and compared with those of the isolates. PMID- 11767122 TI - Evaluation of Bayesian predictability of vancomycin concentration in patients with various degrees of renal function. AB - To assess the usefulness of the population pharmacokinetic parameters of vancomycin (VCM) based on a two-compartment model in Japanese adult patients, predictability by a Bayesian method was evaluated using a concentration time course after single dosing to 22 patients with various degrees of renal function. Using one or two points from the observed data for each patient, the concentrations predicted by a Bayesian method were compared with the observed data for each sampling time. The patients were separated into five groups based on their renal functions indicated by creatinine clearance, and the mean prediction error (MPE) and root mean squared error (RMSE) were calculated for each group as measures of accuracy and precision, respectively. In both one- and two-point methods, the absolute MPE values at each sampling time in the elimination phase were less than 2.5 microg/ml, and the RMSE values were also small. No clear differences were found in MPE and RMSE among the groups. In the distribution phase, the MPE and RMSE were somewhat greater, and RMSE in some groups was around 15 microg/ml when trough data was used to predict the peak concentration. Also, the theoretical RMSE using this population parameter setting could well explain the observed RMSE. These results confirmed this population parameter setting is useful for at least predicting concentration in the elimination phase after single dosing, and the predictability was independent of renal function. PMID- 11767123 TI - Effect of culture conditions on the biosynthesis of gagaminine, a potent antioxidant from the roots of Cynanchum wilfordii. AB - Gagaminine, a steroidal alkaloid isolated from the roots of Cynanchum wilfordii, exhibited potent inhibitory effects on the aldehyde oxidase activity and lipid peroxidation. To find a possible means of mass production of this active component, which will be useful for animal tests, we synthesized it by an in vitro culture method using various growth conditions. Calli were induced from the explants of this medicinal plant and cultivated under culture conditions which varied in light, and the kinds and concentration of plant growth regulators. The production of gagaminine was found to be significantly higher in the dark than in the light. The best gagaminine content (0.960%) was obtained after cultivation of stems on the medium containing 2,4-dichlorophenoxyacetic acid (2,4-D, 2.0 mg/l) only. However, gagaminine was not detected by the mixture of 2,4-D and kinetin, while the mixtures of 2,4-D/zeatin and 2,4-D/6-benzylaminopurine produced a low content of gagaminine (<0.4%). In addition, suspension medium was much better for the formation of gagaminine than solid medium with an increase from 0.960 to 2.227% yield. These results suggest that gagaminine can be produced massively by in vitro culture using stems under the conditions of dark and 2,4-D on liquid medium. PMID- 11767124 TI - Prevention of the neurotoxicity of the amyloid beta protein by genipin. AB - Genipin, which was shown in our previous investigation to have prominent neuritogenic activity in paraneurons such as PC12h cells, was studied to determine whether it could prevent the toxicity of Alzheimer's amyloid beta protein (Abeta) in cultured hippocampal neurons. Increased release of lactate dehydrogenase from hippocampal neurons after 2 d of Abeta25-35 administration was prevented dose dependently by the addition of genipin 20-40 microm. Morphological observations and trypan blue staining of cells confirmed the protection of hippocampal neurons from Abeta toxicity by genipin. Geniposide had less effect in preventing Abeta toxicity. PMID- 11767125 TI - Clinical aspects of left ventricular diastolic function assessed by Doppler echocardiography following acute myocardial infarction. AB - LV systolic function and dilation after Ml have been extensively studied and have been related to heart failure and cardiac mortality. In recent years, it has been increasingly apparent that LV diastolic dysfunction contributes to signs and symptoms of heart failure and LV diastolic dysfunction is associated with increased mortality rates in patients chronic heart failure independent of systolic function. LV diastolic dysfunction is difficult to assess on basis of clinical examination including chest radiography and electrocardiography. LV diastolic filling has traditionally been evaluated by cardiac catherization with direct measurement of filling pressures and relaxation. However, the invasive approach describing LV compliance and relaxation as the major determinants of LV diastolic function, is not feasible and suitable for routine investigations of diastolic function. Two-dimensional and Doppler echocardiography has become a well accented practical and safe non-invasive method for diagnosis of LV diastolic dysfunction. Combined invasive and echocardiographic studies have shown that analysis of mitral and pulmonary venous flow velocities relate to invasively measured filling pressures and relaxation rate in cardiac diseases. Based on Doppler analysis of mitral and pulmonary venous flow three abnormal LV filling patterns are identified: impaired relaxation, "pseudonormalization" and restrictive. These LV filling patterns have been related to symptoms, relaxation rate, filling pressure and prognosis in patients with restrictive and dilated cardiomyopathy. The Doppler flow profiles are influenced by several factors including age, heart rate, load conditions and valve heart diseases which must be taken into consideration during evaluation. During the last decade information about LV diastolic function assessed non-invasively by Doppler echocardiography has gained in patients with CAD. Myocardial ischemia induced by brief coronary artery occlusion or pacing leads to abnormal myocardial relaxation which can be reversed to normal by restoring normal myocardial blood flow. The diastolic abnormality is present within seconds and a characteristic impaired relaxation filling pattern are identified by mitral and pulmonary venous flow analysis. Diastolic dysfunction has been recognized during the early as well during the post-MI phase with or without LV systolic dysfunction. In the acute phase both an abnormal relaxation pattern and restrictive LV filling pattern are present which has been related to in-hospital heart failure. The identification of a pseudonormal or restrictive LV filling pattern are associated with later readmission to hospital with heart failure and cardiac death. Abnormal relaxation filling is the most pronounced filling pattern after one year which might be related to the remodeling process including compensatory hypertrophy, scarring of the infarct zone leading to a non-uniform relaxation of the LV. Remodeling of the LV following a MI is subject to several factors which might involve diastolic function. This is supported by the presence of an impaired relaxation and restrictive filling pattern are associated with progressive LV dilatation following Ml. Furthermore, the LV remodeling process following the very early phase includes the scarring process with collagen deposition in the infarcted and non-infarcted myocardium. The extent and quality of the repair process involving collagen deposition are believed to influence the remodeling process. Increased collagen deposition in the subacute phase of Ml indicated by elevated values of the collagen marker PIIINP is found to be related to LV dilation, depressed systolic function and restrictive LV filling. Development of a restrictive filling in patients with increased collagen deposition might be due to increasing LV volume but also to increased myocardial stiffness. Regarding prognosis diastolic dysfunction seems to be an important marker of outcome as abnormal diastolic properties are related to progressive LV dilatation, development of heart failure and cardiac death following MI. The beneficial effects of BB on morbidity and mortality in post-MI patients are well established. Recently, it has been demonstrated that BB has beneficial effects on progressive CHF and cardiac mortality in patients with chronic heart failure and moderate to severe systolic dysfunction. The mechanisms behind these effects are not fully understood. However, improvement of both systolic and diastolic function during BB therapy are demonstrated in patients with CHF. A few studies in patients with MI indicates that long-term BB therapy improves LV diastolic function which seems to be followed by improvement in systolic function. BB has the potential to lengthening diastole, improving subendocardial myocardial perfusion and affecting symptomatic amd neurohumoral activation following MI which might affect LV systolic and diastolic function and thereby improving outcome. Functional capacity following Ml is a well known predictor for outcome in MI patients. LV diastolic function a closely related to exercise capacity in contrast to measures of systolic function. BB therapy in patients with mild to moderate systolic dysfunction seems to improve exercise capacity which is related to improvement in LV diastolic function. Thus, BB improves exercise capacity and diastolic function by increasing LV compliance which might have prognostic implications. Even though LV systolic and diastolic dysfunction coexist, few two-dimensional and Doppler echocardiographic variables combine measurements of both phases of the cardiac cycle. Recently, the MPI has been suggested as a measure of combined systolic and diastolic myocardial performance which is based on Doppler time intervals of the systolic and diastolic phases. The MPI is easily obtained, reproducible, non geometric and seems less dependent on heart rate and load conditions compared to traditional Doppler measurements. In patients with MI is has shown to reflect disease severity and contain prognostic information. The assessment of MPI seems therefore to be a relevant attractive alternative to established measurements of LV function following MI. PMID- 11767126 TI - Impact of microvascular alterations in heart failure. Effect of cardiac transplantation and ACE inhibition. PMID- 11767127 TI - Serological tumor markers for monitoring breast cancer. PMID- 11767128 TI - Intrauterine growth restriction. Identification, correlation and causation evaluated by use of ultrasound. PMID- 11767129 TI - Antibacterial prophylaxis with trimethoprim-sulfamethoxazole during induction treatment for acute lymphoblastic leukemia. AB - BACKGROUND AND PURPOSE: Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression. Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments. The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy. MATERIAL AND METHODS: Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark. Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode. RESULTS: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)). Nineteen different species were isolated from the blood stream before start of antibiotic treatment. In the non-prophylaxis group there was a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli and P. aeruginosa. There was no difference in the mortality between the two groups (p=0.44). There were no cases of P carinii pneumonia in the period of induction therapy. CONCLUSION: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness. PMID- 11767130 TI - Comment on "Determination of chlormequat in pears by liquid chromatography/mass spectrometry" by H.G.J. Mol, R.C.J. Van Dam, R.J. Vreeken, and O.M. Steijger (J. AOAC Int. 83, 742-747). PMID- 11767131 TI - Novel approach to the study of the chiral discrimination mechanism in a series of dansyl amino acids. AB - With poly(octadecylsiloxane) as the liquid chromatographic stationary phase, phosphate buffer as the mobile phase, a series of D- and L-dansyl amino acids as solutes, and beta-cyclodextrin as the chiral selector, a study was conducted of the hydrophobic effect on both the solute complexation with the chiral selector and chiral discrimination mechanisms by varying the sucrose concentration in the mobile phase and the column temperature. The number of sucrose molecules excluded during the solute complexation with the chiral selector proved to be a good marker of the solute inclusion in the cavity. Gibbs Helmotz parameters delta(deltaH) and delta(deltaS) between D- and L-enantiomers were determined from plots of the logarithm of the intrinsic selectivity versus the reciprocal of the temperature. The results obtained predicted that the enantioselectivity was related to the bulkiness of the solute. This numerical approach is a valuable tool in the exploration of the steric effects implied in the formation of the host-guest complex. PMID- 11767132 TI - Quantitation of antihistamines in pharmaceutical preparations by liquid chromatography with a micellar mobile phase of sodium dodecyl sulfate and pentanol. AB - A reversed-phase liquid chromatographic procedure with a micellar mobile phase of sodium dodecyl sulfate (SDS), containing a small amount of pentanol, was developed for the control of 7 antihistamines of diverse action in pharmaceutical preparations (tablets, capsules, powders, solutions, and syrups): azatadine, carbinoxamine, cyclizine, cyproheptadine, diphenhydramine, doxylamine, and tripelennamine. The retention times of the drugs were <9 min with a mobile phase of 0.15M SDS-6% (v/v) pentanol. The recoveries with respect to the declared compositions were in the range of 93-110%, and the intra- and interday repeatabilities and interday reproducibility were <1.2%. The results were similar to those obtained with a conventional 60 + 40 (v/v) methanol-water mixture, with the advantage of reduced toxicity, flammability, environmental impact, and cost of the micellar-pentanol solutions. The lower risk of evaporation of the organic solvent dissolved in the micellar solutions also increased the stability of the mobile phase. PMID- 11767133 TI - Determination of gliclazide in pharmaceutical preparations by capillary gas chromatography with cool on-column injection and elimination of the matrix effect. AB - Conditions were established for the identification and quantitation of gliclazide in pharmaceutical preparations by capillary gas chromatography with flame ionization detection and cool on-column injection. Gliclazide was extracted with methanol and, after filtration, assayed on a (25 m x 0.25 mm id, 0.2 microm film thickness) CP-WAX 58 (FFAP)-CB WCOT fused silica column. Because the available preparations were of various origins and, therefore, could differ in auxiliary substances and their qualitative parameters, the influence of the matrix constituents on the analytical results was taken into account. Good separation conditions were established for the developed method. The retention time of gliclazide is about 36 min and differs from the retention times of the internal standard (approximately 29 min) and additional peaks present in chromatograms (20 26 min), which were assigned to matrix constituents. The recoveries of gliclozide were high and reached 96.5%. The developed method is characterized by selectivity and precision (relative standard deviation 0.38-1.26%), a wide range of linearity (0.1-10.0 mg/mL), and a limit of detection of 30 ng. In addition, the results of chromatographic analyses calculated in 3 ways were compared with those obtained by UV spectrophotometry. The suggested technique of cool on-column injection, in contrast with split-splitless injection (used in preliminary investigations), reduces to a minimum the possibility of thermal decomposition of gliclazide. PMID- 11767134 TI - Simultaneous densitometric determination of indomethacin and its degradation products, 4-chlorobenzoic acid and 5-methoxy-2-methyl-3-indoleacetic acid, in pharmaceutical preparations. AB - A densitometric method was developed for the identification and determination of indomethacin and its degradation products, 4-chlorobenzoic acid and 5-methoxy-2 methyl-3-indoleacetic acid, in pharmaceuticals. To separate these compounds, silica gel-coated thin-layer chromatography plates and the following mobile phase were used: 2-propanol-25% ammonia-water (8 + 1 + 1, v/v). UV densitometric measurements were made by comparing the absorption spectra and Rf values of appropriate standards with the pharmaceutical preparations examined. The conditions for separation were established and a low detection limit was obtained. Average recoveries were 100.69, 90.09, and 91.17% for indomethacin, 4 chlorobeznzoic acid, and 5-methoxy-2-methyl-3-indoleacetic acid, respectively. PMID- 11767135 TI - Fatty acid composition of Chlorella and Spirulina microalgae species. AB - Two New Age foods which contain high concentrations of whole food nutrients are the single-celled microalgae Chlorella and Spirulina. They are accepted as functional foods, which are defined as products derived from natural sources, whose consumption is likely to benefit human health and enhance performance. These foods are used as a supplement/ingredient or as a complete food to enhance the performance and state of the human body, or improve a specific bodily function. Functional foods are used mainly as products to nourish the human body after physical exertion or as a preventive measure against ailments. We determined the fatty acid compositions, particularly polyunsaturated fatty acid compositions, of Chlorella and Spirulina by capillary column-gas chromatography. The data obtained show that Spirulina contains unusually high levels of gamma linolenic acid, an essential polyunsaturated fatty acid. PMID- 11767136 TI - Simultaneous determination of losartan and hydrochlorothiazide in combined dosage forms by first-derivative spectroscopy and high-performance thin-layer chromatography. AB - Losartan (LST) is the first orally active nonpeptide angiotensin-II receptor antagonist with an improved safety and tolerability profile. It is prescribed alone or in combination with hydrochlorothiazide (HCTZ) for the treatment of moderate-to-severe hypertension. This paper describes the development of 2 methods that use different techniques, first-derivative spectroscopy and high performance thin-layer chromatography (HPTLC), to determine LST and HCTZ in the presence of each other. LST and HCTZ in combined preparations were quantitated by using the first-derivative responses at 271.6 nm for LST and 335.0 nm for HCTZ in spectra of their solutions in water. The linearity ranges are 30-70 microg/mL for LST and 7.5-17.5 microg/mL for HCTZ with correlation coefficients of 0.9998 and 0.9997, respectively. In the HPTLC method, a mobile phase of chloroform-methanol acetone-formic acid (7.5 + 1.5 + 0.5 + 0.03, v/v) and a prewashed Silica Gel G60 F254 TLC plate as the stationary phase were used to resolve LST and HCTZ in a mixture. Two well-separated and sharp peaks for LST and HCTZ were obtained at Rf values of 0.61+/-0.02 and 0.41+/-0.02, respectively. LST and HCTZ were quantitated at 254.0 nm. The linearity ranges obtained for the HPTLC method are 400-1200 and 100-300 ng/spot with corresponding correlation coefficients of 0.9944 and 0.9979, for LST and HCTZ, respectively. Both methods were validated, and the results were compared statistically. They were found to be accurate, specific, and reproducible. The methods were successfully applied to the estimation of LST and HCTZ in combined tablet formulations. PMID- 11767137 TI - Development and validation of a chiral liquid chromatographic method for the determination of atenolol and metoprolol enantiomers in tablet preparations. AB - Atenolol (AT) and metoprolol (MT) are predominantly used in the treatment of angina pectoris, certain arrhythmias, systemic hypertension, and several other cardiovascular disorders. Both compounds are produced commercially in the racemic form, although the S-form is responsible for the desired biological effect. This paper describes a simple, rapid, precise, and accurate method for separating the enantiomers of AT and MT. AT isomers are separated by using a Chiralcel OD column (250 x 4.6 mm, 10 microm), hexane-ethanoldiethylamine-acetic acid (60 + 40 + 0.2 + 0.2, v/v/v/v) as the mobile phase, and a flow rate of 1.0 mL/min. MT isomers are separated by using a mobile phase with the same components in the following proportions (40 + 60 + 0.2 + 0.2, v/v/v/v) and a flow rate of 0.8 mL/min. Ultraviolet detection was at 276 nm for both analytes. The coefficients of variation (CVs) and average recoveries (ARs) for the R-enantiomers in samples A, B, C, D, and E were 1.15 and 101.06%, 0.74 and 99.25%, 1.05 and 102.57%, 0.84 and 101.57%, and 0.86 and 98.62%, respectively. The CVs and ARs for the S-enantiomers in samples A, B, C, D, and E were 1.33 and 98.87%, 0.99 and 100.76%, 1.17 and 101.69%, 1.26 and 100.39%, and 1.40 and 99.39%, respectively. The standard curves of R-AT, S-AT, R-MT, and S-MT showed good linearity over the concentration range studied with correlation coefficients of 0.9991, 0.998, 0.9988, and 0.999, respectively. PMID- 11767138 TI - Improved method for determination of abamectin and ivermectin in cattle plasma. AB - A liquid chromatographic (LC) method was developed for determination of abamectin (ABM) and ivermectin (IVM) in cattle plasma. The sample was extracted with acetonitrile and cleaned up on an alumina column. After conversion to stable fluorescent derivative with trifluoroacetic anhydride and N-methylimidazole, the sample was analyzed by LC with fluorescence detection (Ex 365 nm and Em 475 nm). Doramectin was used as an internal standard. Recoveries ranged from 91.2 to 100.7% for IVM and from 87.0 to 98.7% for ABM, with 1-50 ng/mL fortified samples. The coefficients of variation were <10.1%. The limit of detection was 0.02 ng/mL for ABM and IVM in 1.0 mL samples. PMID- 11767139 TI - Selective liquid chromatographic method for determination of fluoxetine in plasma. AB - A selective and sensitive liquid chromatographic method was developed for the determination of fluoxetine (FLU) in plasma. FLU was isolated from plasma by liquid-liquid extraction. The chromatographic separation was performed on an analytical 250 x 3.9 mm id Novapak C18 column (4 microm particle size) with an isocratic mobile phase consisting of phosphate buffer-acetonitrile-methanol triethylamine (58 + 30 + 10 + 2, v/v) adjusted to pH 7. Using UV detection at 226 nm, the detection limit for FLU in plasma was 3 ng/mL. No interferences were found with tricyclic antidepressant drugs, which allows this method to be used in clinical studies. The calibration curve was linear over the concentration range of 10-200 ng/mL. The average recovery was about 80% for plasma. The inter- and intraday assay coefficients of variation were <8%. PMID- 11767140 TI - Liquid chromatographic determination of simple phenolic compounds in waste waters from olive oil production plants. AB - A method was developed for the determination of simple phenolic compounds (PCs) in waste waters from olive oil production plants by liquid chromatography (LC). The sample under examination was acidified to pH 2 to precipitate proteins, acetone was added to eliminate the colloidal fraction, and hexane was used for extraction to eliminate lipidic substances. The solution obtained was filtered and injected into the LC system; the wavelength selected for the spectrophotometric detection was specific for PCs, so that carbohydrates, organic acids, and short-chain free fatty acids did not interfere. Recoveries of 9 PCs spiked to a real sample were 90-100% for concentrations ranging from 20 to 2000 mg/L for each analyte. PMID- 11767141 TI - Simultaneous determination of binary mixtures of sulfonylurea herbicides in water by first-derivative photochemically induced spectrofluorimetry. AB - First-derivative photochemically induced spectrofluorimetry (PIF-1D) is applied to the simultaneous determination of binary mixtures of 4 sulfonylurea herbicides in aqueous micellar samples. Synthetic binary mixtures of sulfometuronmethyl with chlorsulfuron, metsulfuron-methyl, and 3-rimsulfuron, respectively, are well resolved by using the zero-crossing point procedure. PIF-1D allows the determination of binary mixtures of these herbicides with linear dynamic ranges over about 2 orders of magnitude, limits of detection between 0.5 and 52 ng/mL, and relative standard deviations within 0.3-2.9%. Application to the determination of binary mixtures of these herbicides in spiked tap water samples yielded satisfactory recoveries (90-117%). PMID- 11767142 TI - Broad-spectrum determination of pesticides in groundwater by gas chromatography with electron capture detection, nitrogen-phosphorus detection, and tandem mass spectrometry. AB - Gas chromatography with electron capture detector (ECD), nitrogen-phosphorus detector (NPD), and tandem mass spectrometry (MS/MS) was used to identify 36 pesticides, widely used to control various pest and diseases in vegetables, in water after a preconcentration step on C18 cartridges. The recoveries obtained ranged from 70 to 135% at a fortification level of 100 ng/L with relative standard deviations of <36.2%. The limits of detection and quantitation were < or =48 and < or =160 ng/L, respectively. Important advantages of MS/MS over ECD and NPD in the determination of pesticides are also presented. The proposed analytical methodology was applied to the determination of pesticides in groundwater samples from an agricultural area, the Campo de Dalias (Almeria, Spain). The most frequently encountered pesticides were endosulfan sulfate and metalaxyl, whereas the pesticide found at the highest concentration was fenamiphos. PMID- 11767143 TI - Speciation analysis of heavy metals in natural waters: a review. AB - Metal speciation in natural waters is of increasing interest and importance because toxicity, bioavailability, environmental mobility, biogeochemical behavior, and potential risk in general are strongly dependent on the chemical species of metals. This paper provides an overview of the need for speciation of heavy metals in natural waters, the chemical and toxicological aspects of speciation, and the analytical procedures for separation and the different techniques for final determination that are used today. The trends and developments of speciation are also discussed. Finally, the case of chromium (Cr) was selected for a detailed presentation because the speciation of this metal has attracted a great deal of interest in view of the toxic properties of Cr(VI). PMID- 11767144 TI - Liquid chromatography/electrospray ionization/isotopic dilution mass spectrometry analysis of n-(phosphonomethyl) glycine and mass spectrometry analysis of aminomethyl phosphonic acid in environmental water and vegetation matrixes. AB - A liquid chromatography/electrospray/mass spectrometry (LC/ES/MS) method was developed for the analysis of glyphosate (n-phosphonomethyl glycine) and its metabolite, aminomethyl phosphonic acid (AMPA) using isotope-labelled glyphosate as a method surrogate. Optimized parameters were achieved to derivatize glyphosate and AMPA using 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer prior to a reversed-phase LC analysis. Method spike recovery data obtained using laboratory and real world sample matrixes indicated an excellent correlation between the recovery of the native and isotope-labelled glyphosate. Hence, the first performance-based, isotope dilution MS method with superior precision, accuracy, and data quality was developed for the analysis of glyphosate. There was, however, no observable correlation between the isotope labelled glyphosate and AMPA. Thus, the use of this procedure for the accurate analysis of AMPA was not supported. Method detection limits established using standard U.S. Environmental Protection Agency protocol were 0.06 and 0.30 microg/L, respectively, for glyphosate and AMPA in water matrixes and 0.11 and 0.53 microg/g, respectively, in vegetation matrixes. Problems, solutions, and the method performance data related to the analysis of chlorine-treated drinking water samples are discussed. Applying this method to other environmental matrixes, e.g., soil, with minimum modifications is possible, assuring accurate, multimedia studies of glyphosate concentration in the environment and the delivery of useful multimedia information for regulatory applications. PMID- 11767145 TI - Application of membrane filters for spectrophotometric determination of cationic surfactants in river water and sediment. AB - Cationic surfactant (CS+) in urban river water and sediment was extracted and determined spectrophotometrically with 2 membrane filters. The CS+ in the water samples, mostly in the form of an ion associate with the coexisting anionic surfactant (AS), was collected on a polytetrafluoroethylene (PTFE) membrane filter and eluted with methanol. Bromphenol blue (BPB), hydrochloric acid, and water were added to the methanol solution successively, and the mixed solution was filtered through a mixed cellulose ester membrane filter. The CS+-BPB- ion associate, formed by a counter ion exchange, was collected on the filter and dissolved into N,N-dimethylformamide (DMF) together with the mixed cellulose ester membrane filter. After addition of 2 drops of triethanolamine, the absorbance of the DMF solution was measured. The CS+ in sediment samples was extracted with methanol by ultrasonic irradiation; the methanol solution was then passed through a PTFE membrane filter and evaporated to dryness. The CS+ was redissolved in a small amount of methanol. For water samples, recoveries and relative standard deviations for 0.30 microM benzyldimethyl-tetradecylammonium ion, a standard material, were > or =93 and < or =5%, with a detection limit of 0.02 microM. Concentrations of CS+ in sediments were much higher than those in water samples, indicating that CS+ is adsorbed on the surface of the sediment. PMID- 11767146 TI - Production and use of BCR reference materials for quality assurance in environmental analysis: an update. AB - Reference materials represent an invaluable tool for analytical quality control. Certified Reference Materials (CRMs) are used for the validation of methods, whereas various types of (uncertified) Reference Materials (RMs) are used for routine quality control (establishment of control charts) and interlaboratory testing (e.g., proficiency testing). This paper provides background information on the production and use of environmental RMs and describes recent CRMs produced by the BCR (European Commission) for quality assurance in environmental analysis. PMID- 11767147 TI - Post process product control of rendering plant sterilization conditions by ELISA. AB - Experiments were conducted in a laboratory autoclave and in a commercial rendering plant to set a limit for the R-value of an enzyme-linked immunosorbent assay (ELISA) to prove that animal meal had been sufficiently heat-treated. The immunoassay method is currently the only technique used to check for appropriate sterilization of animal meal. The results of these experiments were statistically assessed using operation characteristic curves and confirmed that insufficiently heat-treated animal meal has an R-value > 2. Results of the trials also demonstrated that the main parameters of sterilization, temperature, and duration strongy influence the R-value, thus indicating that deviation from the target sterilization conditions is verifiable by the ELISA method. PMID- 11767148 TI - Levels of seven PCBs used as markers of dioxin in commercial pork meat in Spain. AB - The levels of 7 PCBs used as markers of dioxin in 62 pork meat samples (head, loin, and dewlap) were determined by supercritical fluid extraction and gas chromatography with electron capture detection. Analytical limits of detection for the individual congeners ranged from 0.048 to 0.2 ng/g dry wt. PCB congeners 153 and 180 were detected in all samples. Among congeners in general, PCB 52, 101, and 153 were the most abundant. There was a linear relationship with a good correlation between PCB 101 and PCB 52. PMID- 11767149 TI - Application of sec-butanol to the derivatization of hydroxyfuranones. AB - This paper reports the use of sec-butanol for the derivatization of chlorinated hydroxyfuranones. The following hydroxyfuranones were investigated: 3,4-dichloro 5-hydroxy-2(5H)-furanone, 3,4-dibromo-5-hydroxy-2(5H)-furanone, 3-chloro-4 (chloromethyl)-5-hydroxy-2(5H)-furanone, and 3-chloro-4-methyl-5-hydroxy-2(5H) furanone. Their derivatization products were analyzed by gas chromatography/mass spectrometry. The sec-butyl derivatives of the hydroxyfuranones investigated yield ions that are less abundant than those obtained for the corresponding isopropyl derivatives. However, sec-butyl derivatives are easily detectable in especially dirty matrixes because they produce double peaks in the chromatogram. The ion intensity of the first peak in the pair is lower than that of the second peak, but both are characterized by the same spectrum. The formation of multiple peaks is related to the formation of diastereoisomers during derivatization. PMID- 11767150 TI - Analysis of agricultural commodities and foods for Alternaria mycotoxins. AB - Fungi of the genus Alternaria are parasitic on plants and other organic materials. A. alternata is a frequently occurring species of particular interest because it produces a number of mycotoxins, including alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT), altertoxins I, II, and III (ATX-I, -II, and -III), and L-tenuazonic acid (TeA). Cleanup procedures of analytical methods for foods and foodstuffs include solvent partition, generally used for TeA, and solid-phase extraction columns for AOH, AME, and ATX-I. These Alternaria mycotoxins have been determined by TLC, GC, and more usually LC, mainly with ultraviolet detection, although fluorescence and electrochemical detection have also been used for Alternaria toxins other than TeA. A Zn2+ salt is usually added to the LC mobile phase for TeA. Recently, atmospheric pressure chemical ionization and electrospray LC/MS and LC-MS/MS have been applied to the determination and confirmation of AOH and AME in apple juice and other fruit beverages at sub ng/mL levels. Natural occurrences of AOH, AME, and in some cases other Alternaria toxins have been reported in various fruits, including tomatoes, olives, mandarins, melons, peppers, apples, and raspberries. They have been found also in processed fruit products such as apple juice, other fruit beverages and tomato products, wheat and other grains, sunflower seeds, oilseed rape meal, and pecans. PMID- 11767151 TI - Determination of ochratoxin A in wine and beer by immunoaffinity column cleanup and liquid chromatographic analysis with fluorometric detection: collaborative study. AB - The accuracy, repeatability, and reproducibility characteristics of a liquid chromatographic method for the determination of ochratoxin A (OTA) in white wine, red wine, and beer were established in a collaborative study involving 18 laboratories in 10 countries. Blind duplicates of blank, spiked, and naturally contaminated materials at levels ranging from < or =0.01 to 3.00 ng/mL were analyzed. Wine and beer samples were diluted with a solution containing polyethylene glycol and sodium hydrogen carbonate, and the diluted samples were filtered and cleaned up on an immunoaffinity column. OTA was eluted with methanol and quantified by reversed-phase liquid chromatography with fluorometric detection. Average recoveries from white wine, red wine, and beer ranged from 88.2 to 105.4% (at spiking levels ranging from 0.1 to 2.0 ng/mL), from 84.3 to 93.1% (at spiking levels ranging from 0.2 to 3.0 ng/mL), and from 87.0 to 95.0% (at spiking levels ranging from 0.2 to 1.5 ng/mL), respectively. Relative standard deviations for within-laboratory repeatability (RSDr) ranged from 6.6 to 10.8% for white wine, from 6.5 to 10.8% for red wine, and from 4.7 to 16.5% for beer. Relative standard deviations for between-laboratories reproducibility (RSDR) ranged from 13.1 to 15.9% for white wine, from 11.9 to 13.6% for red wine, and from 15.2 to 26.1% for beer. HORRAT values were < or =0.4 for the 3 matrixes. PMID- 11767152 TI - Determination of fumonisins B1 and B2 in corn and corn flakes by liquid chromatography with immunoaffinity column cleanup: collaborative study. AB - A liquid chromatographic (LC) method for the determination of fumonisins B1 (FB1) and B2 (FB2) in corn and corn flakes was collaboratively studied by 23 laboratories, which analyzed 5 blind duplicate pairs of each matrix to establish the accuracy, repeatability, and reproducibility characteristics of the method. Fumonisin levels in the corn ranged from <0.05 (blank) to 1.41 microg/g for FB1 and from <0.05 to 0.56 microg/g for FB2, whereas in the corn flakes they ranged from <0.05 to 1.05 microg/g for FB1 and from <0.05 to 0.46 microg/g for FB2. The method involved double extraction with acetonitrile-methanol-water (25 + 25 + 50), cleanup through an immunoaffinity column, and LC determination of the fumonisins after derivatization with o-phthaldialdehyde. Relative standard deviations for the within-laboratory repeatability (RSDr) of the corn analyses ranged from 19 to 24% for FB1 and from 19 to 27% for FB2; for the corn flakes analyses, RSDr ranged from 9 to 21 % for FB1 and from 8 to 22% for FB2. Relative standard deviations for the between-laboratories reproducibility (RSDR) of the corn analyses ranged from 22 to 28% for FB1 and from 22 to 30% for the FB2; for corn flakes analyses, RSDR ranged from 27 to 32% for FB1 and from 26 to 35% for FB2. Mean recoveries of FB1 and FB2 from corn spiked with FB1 at 0.80 microg/g and with FB2 at 0.40 microg/g were 76 and 72%, respectively; for corn flakes spiked at the same levels recoveries were 110 and 97% for FB1 and FB2, respectively. HORRAT ratios for the analyses of corn ranged from 1.44 to 1.53 for FB1 and from 0.96 to 1.48 for FB2, whereas for corn flakes they ranged from 1.60 to 1.82 for FB1 and from 1.39 to 1.68 for FB2. PMID- 11767153 TI - Method of determination of appropriate heat treatment of animal meal by immunoassay developed for detection of cooked beef: interlaboratory study. AB - An interlaboratory trial was conducted for the validation of an enzyme-linked immunosorbent assay (ELISA) method for determination of appropriate heat treatment of animal meal. A commercially available ELISA test kit developed for the identification of beef in cooked food was used in the study. Twelve laboratories from 7 European countries examined 2 different analytical protocols to establish the most appropriate analytical method. Three different samples were used, 2 animal waste materials sterilized at 129 and 134 degrees C (wet conditions), respectively, and a meat and bone meal material processed at dry conditions (maximum temperature, 140 degrees C). Statistical evaluation applying t-statistics showed that the animal meal treated according to European legislation (>133 degrees C) was clearly distinguishable from the 2 other test materials at a 99% confidence level using both analytical protocols. This method can be considered as a complementary test to the immunoassay developed for the detection of pork in cooked food that is already applied in routine analysis for the surveillance of rendering plants. PMID- 11767154 TI - Semiautomatic flow-injection method for determination of volatile acidity in wines. AB - A flow-injection (FI) method based on analytical pervaporation was assessed for its routine use in the determination of volatile acidity in winery laboratories. The new method was compared with both the official method and the Mathieu method, which is most often used in Spanish wineries, by testing 30 different wines, including young and aged, and sweet and dry wines from Montilla-Moriles appellation d'origine. The robustness of the new method was established, and then all 3 methods were studied in terms of range of linearity and regression of the calibration curve, repeatability, reproducibility, sensitivity, detection and quantitation limits (LOD and LOQ, respectively), and time of analysis. The FI method surpassed the Mathieu method in reproducibility and both the Mathieu and official methods in LOD and LOQ and sensitivity; it also required less personnel involvement and shorter analysis time. The statistical criteria established by the Office International de la Vigne et du Vin were applied to the data and the results obtained indicated that the differences between the analytical parameters of the 3 methods are not significant and can be applied indistinctly. The correlation of the methods was studied by taking them 2 by 2, and the corresponding equations, coefficients, and deviations confirmed the statistical results. Thus, the new method can be used in winery laboratories with clear advantages over its 2 counterparts (the routine and official methods). PMID- 11767155 TI - Enzyme assay for identification of pectin and pectin derivatives, based on recombinant pectate lyase. AB - A simple method was developed for fast identification of pectin, based on a recombinant endopectate lyase cloned from Aspergillus niger. When pectin was demethylated and treated with pectate lyase, beta-elimination occurred, resulting in a double bond between C-4 and C-5 in the galacturonic acid residue of the released nonreducing end. The formation of double bonds produced an increase in light absorption, which was detected at 235 nm. The assay was tested on pectin of different origins (apple, orange, sugar beet, sunflower, celery, lemon), pectin derivatives (amidated pectin), and speciality types such as low molecular weight and low %DE (degree of esterification, percentage of galacturonic acid groups esterified with methanol) pectin. The highest response was given by pectate (pectin with %DE< 5) and the lowest by pectin extracted from sugar beet. No other gums (carboxymethylcellulose, carrageenan, locust bean gum, tragacanth, gellan, tamarind, xanthan, amylogum, sodium alginate, or agar) gave any response. Members of IPPA (International Pectin Producers Association) have evaluated the validity of the assay in a ring test. All members of the Association were able to identify pectin from other gums in a blind test. The method can replace more laborious and ambiguous identification tests which exist today. PMID- 11767156 TI - Validation of PCR methods for quantitation of genetically modified plants in food. AB - For enforcement of the recently introduced labeling threshold for genetically modified organisms (GMOs) in food ingredients, quantitative detection methods such as quantitative competitive (QC-PCR) and real-time PCR are applied by official food control laboratories. The experiences of 3 European food control laboratories in validating such methods were compared to describe realistic performance characteristics of quantitative PCR detection methods. The limit of quantitation (LOQ) of GMO-specific, real-time PCR was experimentally determined to reach 30-50 target molecules, which is close to theoretical prediction. Starting PCR with 200 ng genomic plant DNA, the LOQ depends primarily on the genome size of the target plant and ranges from 0.02% for rice to 0.7% for wheat. The precision of quantitative PCR detection methods, expressed as relative standard deviation (RSD), varied from 10 to 30%. Using Bt176 corn containing test samples and applying Bt176 specific QC-PCR, mean values deviated from true values by -7to 18%, with an average of 2+/-10%. Ruggedness of real-time PCR detection methods was assessed in an interlaboratory study analyzing commercial, homogeneous food samples. Roundup Ready soybean DNA contents were determined in the range of 0.3 to 36%, relative to soybean DNA, with RSDs of about 25%. Taking the precision of quantitative PCR detection methods into account, suitable sample plans and sample sizes for GMO analysis are suggested. Because quantitative GMO detection methods measure GMO contents of samples in relation to reference material (calibrants), high priority must be given to international agreements and standardization on certified reference materials. PMID- 11767157 TI - Determination of isoflavones in soy and selected foods containing soy by extraction, saponification, and liquid chromatography: collaborative study. AB - Isoflavones are biologically active compounds occurring naturally in a variety of plants, with relatively high levels found in soybeans. Twelve laboratories participated in a collaborative study to determine the aglycon isoflavone content of 8 test samples of soy and foods containing soy. The analytical method for the determination of isoflavones incorporates a mild saponification step that reduces the number of analytes measured and permits quantitation versus commercially available, stable reference standards. Test samples were extracted at 65 degrees C with methanol-water (80 + 20), saponified with dilute sodium hydroxide solution, and analyzed by reversed-phase liquid chromatography with UV detection at 260 nm. Isoflavone results were reported as microg/aglycon/g or microg aglycon equivalents/g. The 8 test samples included 2 blind duplicates and 4 single test samples with total isoflavone concentrations ranging from approximately 50 to 3000 microg/g. Test samples of soy ingredients and products made with soy were distributed to collaborators with appropriate reference standards. Collaborators were asked to analyze test samples in duplicate on 2 separate days. The data were analyzed for individual isoflavone components, subtotals of daidzin-daidzein, glycitin-glycitein, and genistin-genistein, and total isoflavones. The relative standard deviation (RSD) for repeatability was 1.8-7.1%, and the RSD for reproducibility was 3.2-16.1% for total isoflavone values of 47-3099 microg/g. PMID- 11767158 TI - Determination of rendering plant sterilization conditions using a commercially available ELISA test kit developed for detection of cooked beef. AB - A commercially available enzyme-linked immunosorbent assay (ELISA) test kit developed for detection of cooked beef in meat samples was used to determine appropriate heat treatment of rendered materials. An improved extraction procedure increased the absolute difference in R-values between 2 rendered materials treated under different conditions (average temperature 129 and 134 degrees C, respectively). To evaluate the influence of the main sterilization parameters on ELISA results, a factorial design approach was used. The parameters investigated were temperature, time, particle size, and meat composition. Lean meat samples containing beef and pork were sterilized under strictly controlled conditions in a laboratory autoclave. The experiments demonstrated that the R values obtained with the ELISA test kit for beef are strongly influenced by temperature and time, whereas particle size has a minor influence. The proportion of bovine material did not have any impact on R-values. Autoclave-processed lean meat samples were analyzed by using an ELISA test kit for pork, which was validated in a collaborative trial. The ELISA test kit for pork proved to be more sensitive for the investigated parameters, thus verifying and extending previous investigations. PMID- 11767159 TI - Determination of Cry9C protein in corn-based foods by enzyme-linked immunosorbent assay: interlaboratory study. AB - The performance of a commercially available enzyme-linked immunosorbent assay kit (Enviro-Logix) was assessed for the determination of Cry9C protein, which is produced by the genetically modified corn StarLink, in 8 types of corn-based foods (starch, refined oil, soft tortillas, tortilla chips, corn flakes, corn puffs, corn muffins, and corn bread) in an interlaboratory study involving 7 laboratories in the United States. The assay kit is a double antibody sandwich and is based on the specific interaction between antibody and antigen. The Cry9C protein analyte is sandwiched between 2 antibodies, one to capture the analyte and the other is conjugated to the enzyme, horseradish peroxidase. The enzyme uses tetramethylbenzidine/peroxide for color development. A strong acid stopping reagent is then used to change the color from blue to a stable yellow. The intensity of the color is proportional to the concentration of the Cry9C protein. In this study blind duplicates of control samples (blank material prepared from non- StarLink corn), spiked samples (blank material with the addition of Cry9C protein), and samples containing incurred analyte (products prepared with StarLink corn) were analyzed. Cry9C protein from 2 different sources was used to spike the food products. Cry9C protein produced and purified from a bacterial host was used to prepare spiked test samples at 2.72 and 6.8 ng/g. Cry9C protein from StarLink corn flour was used to prepare spiked samples at 1.97 ng/g. Average recoveries for samples spiked with corn flour Cry9C protein at 1.97 ng/g ranged from 73 to 122%, within-laboratory relative standard deviations (RSDr) ranged from 6 to 22%, and between-laboratories relative standard deviations (RSDR) ranged from 16 to 56%. Average recoveries for samples spiked with bacterial Cry9C protein at 2.72 and 6.8 ng/g ranged from 27 to 96% and from 32 to 113%, respectively; RSDr values ranged from 10 to 35% and from 7 to 38%, respectively; and the RSDR ranged from 28 to 84% and 15 to 75%, respectively. The incurred test samples were found to contain Cry9C protein at levels ranging from 0.8 to 3187 ng/g depending on the product, RSDr values ranged from 5 to 16% and RSDR values ranged from 11 to 71%. Results of the statistical analysis indicate that this method is applicable to the determination of Cry9C protein in the 8 types of collaboratively studied corn-based products containing Cry9C protein (from StarLink) at levels of > or =2 ng/g. PMID- 11767160 TI - Determination of chlormequat in fruit samples by liquid chromatography electrospray-mass spectrometry/mass spectrometry. AB - An ion-pair liquid chromatography-mass spectrometry/mass spectrometry method was developed for the determination of chlormequat in fruit samples. A solid-phase extraction cleanup procedure with C18 cartridges was used. Sample preparation was simple and the achieved detection limit (0.03 mg/kg) and quantitation limit (0.08 mg/kg) were below the maximum residue levels legislated by the European Union. The chromatographic separation was performed by using a C8 column and heptafluorobutyric acid as ion pair reagent. The detection was conducted with an electrospray source and an ion trap as a mass analyzer. The reproducibility of the method gave good run-to-run (8-9%) and day-to-day (9-13%) precision values, and its applicability to the determination of chlormequat in pears and grapes, purees, and pear, apple, and grape juices was demonstrated. PMID- 11767161 TI - Determination of total metals in cultivated oysters (Crassostrea gigas) from the northwest coast of Mexico by microwave digestion and atomic absorption spectrometry. AB - Bivalves such as oysters often accumulate heavy metals, and therefore can be used to monitor changes of pollutant concentrations in the environment. Cultivated oysters from the northwest coast of Mexico are widely used for human consumption and thus have an important commercial value. Information was gathered on the concentration of these elements in oysters (Crassostrea gigas) cultivated on the coast of Sonora. Oysters were randomly collected from April to October 1997, from 6 different locations (65 individuals per site) in 4 different months. Metals were determined by microwave digestion followed by atomic absorption spectroscopy. The mean values (microg/g fresh weight) for each metal were: Cd, 0.76; Cu, 3.64; Zn, 17.71; Pb, 0.50; As, 0.05; Hg, 0.03; and Se, 0.21. The results show that, except for Cd, concentrations of regulated metals were under the maximum permitted values specified by regulatory agencies of Mexico and were comparable to those reported from other areas. PMID- 11767162 TI - Slurry atomization of wheat-milled fractions for electrothermal atomic absorption spectrometric determination of nickel and chromium. AB - A slurry electrothermal atomic absorption spectrometric technique was used to determine Ni and Cr in wheat flour and its by-products. Slurries (3%, w/v) were prepared in a mixture of 15% HNO3-10% H2O2 as suspended medium. Differences in Ni and Cr contents due to origin and texture of the wheat and to the effects of the milling process were studied. Ni and Cr levels were more markedly influenced by the geographical origin of the wheat than by its texture. Both metals were related to the amount of bran present in each milled fraction and varied over the ranges of 212-298 ng/g (Ni) and 34-85 ng/g (Cr) in flours (with minimal bran contents); 297-460 ng/g (Ni) and 67-118 ng/g (Cr) in shorts; and 424-723 ng/g (Ni) and 106-165 ng/g (Cr) in brans. The Ni and Cr contents were not significantly affected by the technological processes typically performed in a flour-producing factory. PMID- 11767163 TI - Determination of selenium in marine biological tissues by transverse heated electrothermal atomic absorption spectrometry with longitudinal Zeeman background correction and automated ultrasonic slurry sampling. AB - A fast, sensitive, and reliable method for determination of selenium in marine biological tissues by electrothermal atomic absorption spectrometry with slurry sampling was developed. Slurries were prepared from fresh and frozen seafood samples that were previously homogenized, dried, and ground; particle sizes <100 microm were taken for analysis. A 3% (v/v) HNO3 solution containing 0.01% (v/v) Triton X-100 was used as slurry diluent. Slurries were mixed on an automated ultrasonic slurry sampler at 20% amplitude for 30 s just before an aliquot was injected into the furnace. The method was successfully validated against the following certified reference materials: NRCC CRM DORM-2 (Dogfish muscle); NRCC CRM TORT-2 (Lobster hepatopancreas); NRCC CRM DOLT-2 (Dogfish liver); and BCR CRM 278 (Mussel tissue), and was subsequently applied to determination of Se in 10 marine biological samples. The influences of the drying procedure (oven-, microwave-, and freeze-drying), matrix modifier amount, mass of solid material in cup, and pipetting sequence are discussed. The limit of determination of Se was 0.16 microg/g and the repeatability, estimated as between-batch precision, was in the range of 4-8%. Se contents in the samples ranged from 0.6 to 2.8 microg/g. The proposed method should be useful for fast assessment of the daily dietary intake of Se. PMID- 11767164 TI - Use of a ruthenium(III), iron(II), and nickel(II) hexacyanometallate-modified graphite electrode with immobilized oxalate oxidase for the determination of urinary oxalate. AB - This paper describes the performance of a biosensor with an Ru(III), Ni(II), and Fe(II) hexacyanometallate-modified graphite electrode and immobilized oxalate oxidase for the determination of urinary oxalate. The addition of ruthenium enhances the electrochemical reversibility and chemical stability of the electrocrystallized layer and improves the sensitivity of the biosensor. Hydrogen peroxide, produced by the enzyme-catalyzed oxidation of oxalate, was measured at 50 mV vs an Hg Hg2CI2 3M KCl electrode in a solution of pH 3.6 succinic buffer, 0.1 M KCl, and 5.4mM ethylenediaminetetraacetic acid. The linear concentration range for the determination of oxalate was 0.18-280 microM. The recoveries of added oxalate (10-35 microM) from aqueous solution ranged from 99.5 to 101.7%, whereas from urine samples without oxalate (or with a concentration of oxalate below the detection limit) the recoveries of added oxalate ranged from 91.4 to 106.6%. The oxalate in 24 h urine samples, taken during their daily routine from 35 infants and children, was measured and found to range from 0.6 to 121.7 mg/L. There were no interferences from uric acid, acetylsalicylic acid, and urea in the concentration range investigated, but paracetamol and ascorbic acid did interfere. A good correlation (R2 = 0.9242) was found between values obtained for oxalate in real urine samples by 2 laboratories, with the proposed biosensor and ion chromatography, respectively. PMID- 11767165 TI - Collection and preparation of sidestream cigarette smoke for trace elemental determinations by graphite furnace atomic absorption spectrometry and inductively coupled plasma mass spectrometry. AB - A novel method for the collection and preparation of sidestream cigarette smoke condensate is described for trace elemental analysis by inductively coupled plasma mass spectrometry and graphite furnace atomic absorption spectrometry. The smoke collection method utilizes a specially designed chimney that collects and directs the sidestream smoke (SS) to a 2-stage trapping system consisting of an impaction trap followed by a 0.8 microm mixed cellulose ester filter. The samples are digested with nitric acid in a commercial heating block before analysis. The method limits of detection (LODs) are 1, 0.2, 2, 9, 6, and 7 ng/cigt for As, Cd, Pb, Ni, Se, and Cr, respectively. The SS collected from an industry reference cigarette, 1R4F, produced by the University of Kentucky was analyzed. The concentrations of As, Cd, and Pb in 1R4F were determined to be 27.3+/-2.1, 412+/ 14, and 43.8+/-2.0 ng/cigt, respectively, while the concentrations of Ni, Cr, and Se are below the method LOD. Consequently, this novel method successfully addresses contamination, instrumentation, and collection issues for performing trace elemental analysis of sidestream cigarette smoke condensate. PMID- 11767166 TI - Sampling grain shipments to detect genetically modified seed. AB - Using the binomial distribution, the effect of sample size on the variability among sample test results when sampling a lot with 1.0% genetically modified (GM) or biotech seed was evaluated. The coefficient of variation, cv, among 500-seed sample test results taken from a lot with truly 1.0% was computed to be 44.5%. Increasing sample size to 1000 seeds reduced the cv among sample test results to 31.5%. The effects of sample size and accept/reject limits on the buyer's risk (bad lots accepted) and the seller's risk (good lots rejected) was also evaluated assuming a tolerance of 1.0% GM seed. Increasing sample size decreases both the buyer's and seller's risks at the same time. Using an accept/reject limit below the regulatory tolerance decreases the buyer's risk, but increases the seller's risk. Using an accept/reject limit above the regulatory tolerance decreases the seller's risk but increases the buyer's risk. PMID- 11767167 TI - Hydrocolloid interferences in the determination of pectin by the carbazole method. AB - In the colorimetric determination of pectin by the carbazole method, some of the interfering compounds have been identified but the possible interference of different hydrocolloids is not known. Several hydrocolloids are currently used in the preparation of imitation and adulterated orange juice for cloud stabilization. Hydrocolloids studied were gum arabic, carboxylmethyl cellulose, sodium alginate, carrageenan, guar gum, and xanthan. The effects of these hydrocolloids on the carbazole method for pectin determination was studied. Procedures are proposed for the correct use of the carbazole method for pectin determination in the presence of extraneous hydrocolloids. PMID- 11767168 TI - Trace elements in western Canadian hard red spring wheat (Triticum aestivum L.): levels and quality assurance. AB - A monitoring program was conducted for trace elements in Western Canadian Hard Red Spring wheat (Triticum aestivum L.). Samples were selected from harvest survey samples submitted by producers from crop districts in Manitoba, Saskatchewan, and Alberta for 1996, 1997, and 1998 crops. The analytical quality control measures used in these surveys are described along with the results for Cd, Cu, Fe, Mn, Se, and Zn. Accuracy and precision for the analyses fell within the acceptable control limits. Year-to-year variations in grain chemistry were small for Cd, Mn, Se, and Zn, but Cu and Fe contents showed 12 and 9% decreases, respectively, over the 3 years. The overall variability for the plant-essential trace elements-Cu, Fe, Mn, and Zn-was low compared with that for Cd and Se. The spatial variation in crop chemistry across the Canadian Prairie wheat-producing region was greater than the year-to-year variations. Soil properties were major factors in controlling Cd and Se levels in grain. PMID- 11767169 TI - Uptake of cadmium, copper, iron, manganese, and zinc in mushrooms (Boletaceae) from Croatian forest soil. AB - The concentration of trace elements (Cd, Cu, Fe, Mn, and Zn) was measured in different species of mushrooms (Boletaceae) and correlated with corresponding elements in soil. Five different species of Boletaceae mushrooms and soil samples were collected from forests of Varazdin county in Croatia. Trace elements were analyzed by atomic absorption spectrometry in mushrooms and in EDTA-extracted soil. The results showed that Cd, Cu, and Zn are concentrated in mushroom tissue from soil with transfer factors (mushroom/soil) of 27.0,10.5, and 12.5, respectively. Cadmium incorporated much less in Leccinum (mean 0.73 mg/kg dry weight) than in Boletus, Xerocomus, or Gyroporus (respective means, 6.8, 8.4, and 12.3 mg/kg). Copper and Zn were accumulated in all collected mushrooms (14.7-35.6 and 109-179 mg/kg, respectively) with no difference among species. There was no accumulation of Fe and Mn in mushrooms, but concentrations differed between species, with lowest values in Leccinum. Iron varied from 31 to 878 mg/kg and Mn from 2.9 to 409 mg/kg. Correlations between elements in mushrooms and soil were significant only for Mn. Because no significant correlations for Cd, Cu, Zn, and Fe between mushrooms and soil were found, more studies are needed with only one species of mushrooms collected at locations with different levels of soil contamination. In spite of higher concentrations of Cd in some Boletaceae species, it is assumed that Cd intake through moderate mushroom consumption remains below suggested Provisional Tolerable Weekly Intake (FAO/WHO). PMID- 11767170 TI - Honey as a candidate reference material for trace elements. AB - The feasibility of producing and certifying new certified reference materials (CRMs) for trace elements in honey was investigated. Preliminary steps for preparation of candidate materials are performed at the Institute for Reference Materials and Measurements, Joint Research Centre of the European Commission (EC JRC-IRMM). Two different types of honey, Acacia and Eucalyptus, were tested for determination of 10 trace elements. To each type of honey was added a given amount of high purity deionized water to obtain aqueous solutions with an acceptable degree of homogeneity which would require only minimal manipulation before analysis. Average values obtained for the trace elements by means of inductively coupled plasma-based techniques were as follows (in microg/ kg +/- SD): Acacia honey, As, 1.10+/-0.20; Cd, 0.328+/-0.035; Cr, 1.90+/-0.22; Cu, 67.0+/-5; Fe, 215+/-30; Hg, < 0.75; Mn, 82.1+/-6.2; Ni, 21.0 3.0; Pb, 2.30+/ 0.25; Se, 9.10+/-1.2; Zn, 167+/-22; Eucalyptus honey, As, 5.99+/-0.10; Cd, 0.592+/-0.074; Cr, 1.50+/-0.07; Cu, 219 24; Fe, 1008+/-114; Hg, <0.75; Mn, 1009+/ 51; Ni, 11.3+/-1.5; Pb, 5.00+/-0.40; Se, 5.60+/-0.91; Zn, 791+/-91. When these 2 pilot materials are ready, the certification project will be launched in full compliance with current rules set by EC-JRC-IRMM. If the project is successful, the new CRMs will be put primarily at the disposal of the National Reference Laboratories for trace elements. PMID- 11767171 TI - Determination of iodine in seafood by inductively coupled plasma/mass spectrometry. AB - A method was developed for determination of total iodine content in different standard reference materials (SRMs) and seafood products by inductively coupled plasma/mass spectrometry (ICP/MS). If iodine is present as iodide and nitric acid is used in the wet digestion system, the observed signal is not stable when iodine is measured by ICP/MS at m/z 127. To stabilize the iodine signal, 3% ammonia solution (1 + 1, v/v) was added to the digest. The limit of quantitation of the method, defined as 6 times the standard deviation in the blank solution (n = 20) was estimated to be 15 mg/kg (using 0.2 g dry mass and a dilution factor of 50). The precision, expressed as repeatability of the iodine concentration, varied between 3.2 and 12% in SRMs, with concentrations of 4.70-0.17 mg/kg dry matter. The described method was compared with a method using tetramethylammonium hydroxide extraction. Both methods showed good precision and trueness by analyses of SRMs. The 2 methods were used to determine iodine in seafood from the Barents Sea, the Norwegian Sea, and the North Sea. The results showed great variation between different fish species as well as between individuals within a species. The lowest values of iodine were recorded in muscle of ling (Molva molva) with a mean of 0.07 mg/kg fresh weight and a variation between 0.03 and 0.11 mg/kg fresh weight. The highest values were found in cod (Gadus morhua) from the Barents Sea, with a mean of 2.5 mg/kg and a variation between 0.7 and 12.7 mg/kg fresh weight. PMID- 11767172 TI - Cadmium and other metals in Swedish wheat and rye flours: longitudinal study, 1983-1997. AB - Wheat flour (sifted), wheat bran, and rye flour were sampled annually in several different areas in Sweden for 15 consecutive years (1983-1997) for a total of 105, 90, and 30 samples, respectively. These samples were analyzed for their content of Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn by atomic absorption spectrophotometry with background correction after dry ashing at 450 degrees C. As part of the quality control procedures, an in-house reference material was analyzed in parallel to the samples to ensure reliability of the results. In addition, a certified reference material was analyzed to monitor accuracy of the results. The Cd level in wheat and rye flours (mean 0.029 and 0.017 mg/kg dry wt, respectively) correlated significantly with time (p < 0.05) in 2 phases, tending to increase during the first half of the period and decrease during the latter half. In wheat bran, Cd (mean 0.15 mg/kg) levels did not correlate significantly with time. In wheat flour, Cu, Mn, and Zn (means 1.7, 6.2, and 7.6 mg/kg, respectively) showed a significant linear increase (p < 0.05) in concentration over time. In rye flour, the levels of Cu, Fe, Mn, and Zn (means 3.8, 36, 30, and 28 mg/kg, respectively) all decreased significantly (p < 0.05) over time. Similarly, in wheat bran Cu (mean 14 mg/kg) increased and Pb (mean 0.027 mg/kg) decreased significantly (p < 0.05) over time, whereas Ni and Zn showed a significant curved correlation with time and peaked at about the middle of the measurement period. PMID- 11767173 TI - Long-term results and determinants of mortality after surgery for native and prosthetic valve endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the long-term results and determinants of mortality after operative treatment of native and prosthetic valve endocarditis at a single institution. METHODS: Between March 1985 and October 1999, 171 patients underwent surgery for native (NVE) or prosthetic valve endocarditis (PVE). NVE was present in 98 patients (57%), and PVE in 73 patients (43%). Mean follow up was 5.6+/-3.9 years (range: 0 to 15 years). RESULTS: Overall hospital mortality was 9.9% (n = 17). Hospital mortality was higher among patients with PVE (15.1%) than those with NVE (6.1%; p = 0.05). Overall survival at 10 years was 46+/-5%. Patients with NVE had a higher 10-year survival rate (53+/-7%) than those with PVE (37+/-7%; p = 0.02). At 10 years, overall freedom from any late complication was 47+/-6% and from residual or recurrent endocarditis was 78+/-5%. Predictors of hospital death were emergency surgery (p <0.003) and preoperative renal insufficiency (p <0.008). Predictors of late death were age >70 years (p <0.002), renal failure (p <0.03) and fungal endocarditis (p <0.04). CONCLUSION: These findings demonstrate the increased perioperative, as well as postoperative, risks associated with PVE versus NVE. Cardiac and extracardiac manifestations of the disease, as well as fungal organisms, but not the activity of the endocarditis, were significant adverse determinants of late outcome. PMID- 11767174 TI - Stroke is not a contraindication for urgent valve replacement in acute infective endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: A treatment dilemma arises when endocarditis is complicated by cerebral embolism. Secondary cerebral hemorrhagic complications may arise following suppression of coagulation during extracorporeal circulation. Extensive valvular vegetation is regarded as an indicator for urgent surgery. The study aim was to determine the relative risk of thromboembolic complications, and to analyze the prognostic influence of different treatment strategies following onset of these complications, in particular, secondary cerebral hemorrhagic events after urgent surgery. METHODS: Between 1978 and 1993, endocarditis was diagnosed in 288 consecutive patients. Patients treated before 1982 (6.9%) were analyzed retrospectively. The remaining patients (93.1%) were followed prospectively (mean 4.3+/-1.7 years). RESULTS: In 50 patients (17.4%), the clinical course was complicated by one embolism, and in 58 patients (20.2%) by recurrent embolisms. In total, 71% of all embolisms were cerebral events. The operated patients were categorized with regard to the time between recurrent thromboembolic events and cardiac surgery (<72 h, 3-8 days, and >8 days). The prognosis for patients operated within 72 h was significantly more favorable (p <0.0001) than for those treated medically. Patients undergoing cardiac surgery more than eight days after stroke, and those treated conservatively, had poor prognoses. CONCLUSION: When endocarditis is complicated by stroke, it is recommended that cardiac surgery be performed within 72 h of the cerebral embolism, when the risk of secondary cerebral hemorrhage appears to be low. Cranial computed tomography is obligatory immediately before surgery in order to identify patients with early reperfusion hemorrhages due to spontaneous fragmentation of the thrombus. In these patients, cardiac surgery must be postponed because of the high risk of severe cerebral bleeding during extensive perioperative anticoagulation, and is only justified in the case of an otherwise unfavorable prognosis. PMID- 11767175 TI - Silzone coating and paravalvular leak: an independent, randomized study. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to address independently, in a randomized patient cohort, the impact of Silzone coating on the prevalence and impact of paravalvular leak in patients undergoing mechanical valve replacement. METHODS: Randomized implantation of the uncoated St. Jude Medical Masters, and the Silzone-coated prosthesis was performed in 95 patients, excluding those with suspected or diagnosed infective endocarditis. The company did not support the study; this cohort is not contained in the AVERT trial. Following recall of the Silzone-coated valves, all patients in this cohort were invited to undergo control transthoracic echocardiography and plasma LDH determination. RESULTS: Silzone-coated valves were implanted in 46 patients (57 valves; 34 aortic, 20 mitral, three tricuspid), and uncoated valves in 49 patients (55 valves; 38 aortic, 16 mitral, one tricuspid). One patient with an uncoated mitral valve died from left ventricular dissection. In total, 73 patients returned for specifically planned echocardiography (mean interval 478+/-78 days). Sixteen patients underwent echocardiography on another occasion (mean interval 113+/-202 days). Six hospital survivors did not undergo any postoperative echocardiography. In total, 51 Silzone-coated valves (31 aortic, 18 mitral, two tricuspid), and 53 uncoated valves (37 aortic, 15 mitral, one tricuspid) were evaluated. No patients were reoperated for intrinsic or extrinsic valve dysfunction. No major paravalvular leaks were seen. Five of 51 Silzone-coated valves showed minimal (grade <1+; four aortic, one mitral) paravalvular leak when specifically sought; two showed minimal (grade <1+; one aortic, one mitral), and one slight (grade 1+; one mitral) paravalvular leak in the uncoated group (p = 0.55). The LDH level was 654+/-163 U/I in the Silzone group, and 598+/-124 U/l in the control group (p = 0.10). CONCLUSION: No differences were detected in the incidence of paravalvular leak between Silzone-coated and uncoated mechanical St. Jude Medical valves. The incidence of major paravalvular leaks appears to be lower in the present cohort than was reported in the AVERT trial. PMID- 11767176 TI - Early investigation of silver-coated Silzone heart valves prosthesis in 126 patients. AB - BACKGROUND AND AIM OF THE STUDY: Permanent silver (Silzone) coating of the sewing cuff of St. Jude Medical prosthetic heart valves may reduce the rate of prosthetic valve endocarditis (PVE). However, the incidence of paravalvular leaks and stroke in patients after implantation of Silzone-coated heart valve prostheses is largely unknown. METHODS: Complications were analyzed among 126 consecutive patients (78 males, 48 females; mean age 64.7 years; range: 40-80 years) who received Silzone-coated prostheses at our institution between February 1998 and December 1999. Among patients, 94 had aortic valve replacement, 29 mitral valve replacement, and three had aortic and mitral valve replacement. Concomitant cardiac procedures (mainly coronary bypass) were performed in 47 patients (37.3%). RESULTS: Hospital mortality was 1.6% (2/126) and freedom from valve-related mortality 99.2+/-0.9%. Total follow up was 137.4 patient-years, and 98.4% complete. Strokes or transitory ischemic attacks (TIAs) occurred in four cases (two strokes, two TIAs; stroke rate 1.5%/year; 95% CI 0.4-2.6%/year; stroke+TIA rate 3%/year; 95% CI 0.4-5.25%/year). There was no case of prosthetic valve dysfunction or PVE. Freedom from reoperation due to procedure-associated complications was 97.6% (one aortic dissection, two major bleeds). Paravalvular leak was detected in 19 cases, and graded trivial or mild in 17 cases (11 grade 0 I, six grade I), and moderate in two cases (grade I-II in one, grade II in one). No patient needed reoperation due to paravalvular leak. Left ventricular (LV) function was normal in 80 cases, but was impaired mildly in 20 cases, moderately in 16, and severely in eight. Bicycle exercise testing in 92 patients (73%) showed median exercise performance (81.4+/-23.9% of normal) after correction for age and weight. Cerebral magnetic resonance imaging was performed in 64 patients (50.8%); median MRI score was 2.0+/-1.8 according to a 12-scaled score system. CONCLUSION: The overall incidence of echocardiographic paravalvular leak graded more than trivial or mild was low (1.6%) in patients followed for a mean of 1.1+/ 0.5 years (range: 1-27 months) after valve replacement with Silzone-coated heart valve prostheses. No patient required reoperation due to paravalvular leak; moreover, the stroke rate (1.5%/year) was low in these patients. The present data indicated no significant disadvantages or higher rate of complications related to silver coating compared with other, non-silver-coated prostheses. Future investigation is needed to determine long-term outcome. PMID- 11767177 TI - Silzone-coated St. Jude medical valve: a safe valve. AB - Careful follow up studies in patients receiving a Silzone-coated St. Jude Medical valve (67 aortic valves, 36 mitral valves, nine double valves) did not support the fear of a high risk of perivalvular leak and embolism rate. Freedom from perivalvular risk at 12 and 24 months follow up was 98.5+/-1.5% and 100% for the aortic and mitral valves, respectively. Freedom from any thromboembolic event was 96.6+/-2.4% at 12 and 24 months follow up in the aortic group, and 97+/-3% at 12 and 24 months in the mitral group. The risk of bleeding (92.2+/-3.8% at 12 and 24 months in the aortic group; 85.5+/-6.0% in the mitral group) illustrated the risk of mechanical valve implantation in an elderly population. PMID- 11767178 TI - A new method for the preservation of aortic valve homografts. AB - BACKGROUND AND AIM OF THE STUDY: Aortic valve homografts were treated with 50% ethanol and glycerol followed by freeze-drying (D-Hydro). Comparative results of fresh versus D-Hydro-treated aortic roots implanted for up to nine months in the descending aorta of sheep with induced aortic regurgitation (AR) are reported. METHODS: Six fresh and six D-Hydro valves were implanted in 12 sheep for three, six and nine months, and echocardiography and pressures were taken at surgery and sacrifice. Tissue sections were stained with hematoxylin and eosin, von Kossa, Masson's trichrome, Movat's pentachrome, von Willebrand factor, CD3 (a T-cell marker) and smooth muscle alpha-actin. RESULTS: No grafts had increased gradients after implantation, or at sacrifice. At explantation, fresh homografts showed early pannus formation followed by thrombus, annular dilatation and wall calcification. Leaflets were thickened and progressively retracted. All had severe AR. The appearance of D-Hydro-treated homografts was normal, except for mild leaflet retraction in three, resulting in AR (in two animals the induced AR had healed). Histologically, a T-cell-mediated reaction was evident in the fresh homografts, and collagen distortion was noted. Calcification was present in all fresh specimens and was severe at nine months. D-Hydro roots showed only minor calcification in the six-month samples. Normal collagen, and a complete layer of von Willebrand factor-stained cells were present at three months. At nine months, cell rehabitation extended for two-thirds of the leaflets (alpha-actin +). The inflammatory reaction was very mild, with CD3+-stained cells absent in most samples. CONCLUSION: Aortic valve homografts treated with the D-Hydro freeze drying method performed better than fresh homografts due to the absence of thrombus and annulus dilatation, limited calcification, and rehabitation of the aortic wall and parts of the leaflet by myofibroblasts, as well as the presence of a complete endothelial layer on the aortic wall and leaflet. PMID- 11767179 TI - Ross operation in children: late results. AB - BACKGROUND AND AIM OF THE STUDY: Although the Ross operation has become the accepted aortic valve replacement in children, the long-term fate of the pulmonary autograft valve remains unknown. To assess mid-term and late results of autograft valve durability, patient survival and valve-related morbidity, a retrospective review of patients (age range: 3 days to 17 years) having a Ross operation between November 1986 and May 2001 were reviewed. METHODS: Medical records and patient contacts with all but two of 167 current survivors of 178 consecutive patients having an aortic valve replacement as a Ross operation have been completed during the past two years. The most recent echocardiographic evaluation was reviewed for autograft valve and homograft valve function. RESULTS: Operative mortality was 4.5% (8/178), with three late deaths (two were non-valve-related) for an actuarial survival of 92+/-3% at 12 years. Actuarial freedom from autograft valve degeneration (reoperation or severe insufficiency of autograft valve or valve-related death) was 90+/-4% at 12 years. Autograft valve degeneration was not affected by technique of insertion (141 root replacement, 37 intra-aortic), aortic valve morphology (157 bicuspid or unicuspid, 26 tricuspid), or age at operation. Autograft valve degeneration was worse in patients with a primary lesion of aortic insufficiency than in those with aortic stenosis (p = 0.03). Autograft valve reoperation was required in 12 patients, with autograft valve replacement in seven. Actuarial freedom from autograft replacement was 93+/ 3% at 12 years. Homograft valve replacement was required in seven patients, with actuarial freedom from replacement of 90+/-4% at 12 years. Eight additional patients have homograft valve obstruction (gradient > or =50 mmHg), and seven have severe pulmonary insufficiency. CONCLUSION: Survival and freedom from aortic valve replacement are excellent in children. Homograft valve late function remains a concern, and efforts to improve homograft durability should be encouraged. PMID- 11767180 TI - The ross operation in 225 patients: a five-year experience in aortic root replacement. AB - BACKGROUND AND AIM OF THE STUDY: The Ross operation, introduced more than 30 years ago, has recently undergone several modifications to improve both technical feasibility and results. At the authors' institution, the Ross operation, performed as root replacement in all cases, was commenced in February 1995. METHODS: A total of 225 patients (177 males, 48 females; mean age 39+/-15 years; range: 2 to 67 years) were operated on up to December 2000. Aortic regurgitation was present in 80 patients, stenosis in 69, and combined disease in 73; prostheses were replaced in three patients. Combined procedures were performed in 51 patients. Nine patients had active endocarditis. Follow up was 98% complete and totaled 471 patient-years. RESULTS: There was no early mortality, and no thromboembolic or hemorrhagic events. Complications included prolonged ventilation in two patients, perioperative myocardial infarction in three, pacemaker implants in three and perioperative bleeding in six. One patient died at 25 months from hemoptysis, and one at five months of unknown cause. In the long term, four patients required reoperation due to autograft regurgitation (one autograft repair, three autograft replacements). Routine aortic annulus support, a lowered threshold in replacing all dilated ascending aorta and keeping the autograft short to the level of the sinotubular junction seems to have prevented further autograft failure. Pulmonary homograft stenosis led to reoperation in one patient. Six patients with elevated gradients are currently under observation. Echocardiography revealed autograft median peak gradients of 5.1+/-2.8 mmHg, pulmonary homograft gradients of 14.2+/-11.5 mmHg, and no significant regurgitation, except in one additional patient with recently diagnosed aortic insufficiency (grade >2). CONCLUSION: Mid-term excellent hemodynamic results, low morbidity and reoperation requirement support the evolved root replacement technique and justify its further utilization. PMID- 11767181 TI - Saccular aneurysm of pulmonary autograft after the Ross procedure. AB - The Ross procedure, which includes removal of the malformed aortic valve and replacement of a pulmonary autograft in the aortic position, has increased the number of available treatment options. Recently, dilatation of the autograft pulmonary root after the Ross procedure has been reported as a complication. We report a patient with bicuspid aortic valve malformations and aortic annulus dilatation, who had a saccular-form, true-type, aneurysm in the pulmonary autograft seven months after the Ross procedure. These changes have not been described so far as complication. Pathologically, marked mucoid degeneration was noted in the tunica media of the aneurysm, as well as in the original aortic root. These findings may suggest similar pathological characteristics between the aorta and pulmonary arteries. Hence, the surgical risks accompanying vascular characteristics in patients with congenital aortic valve malformations should be considered. PMID- 11767182 TI - Ischemic mitral valve regurgitation grade II-III: correction in patients with impaired left ventricular function undergoing simultaneous coronary revascularization. AB - BACKGROUND AND AIM OF THE STUDY: Mitral valve regurgitation (MVR), occurring as a result of myocardial ischemia and global left ventricular (LV) dysfunction, is predictive of poor outcome. The study aim was to assess the feasibility of mitral valve surgery concomitant with coronary artery bypass grafting (CABG) in patients with ischemic MVR grade II-III and impaired LV function. METHODS: Between January 1996 and July 2000, 99 patients with grade II and III ischemic MVR and LV ejection fraction (LVEF) 17-30% underwent either combined mitral valve surgery and CABG (group I, n = 49) or isolated CABG (group II, n = 50). LVEF (%), LV end diastolic diameter (LVEDD; mm), LV end-diastolic pressure (LVEDP; mmHg), LV end systolic diameter (LVESD; mm) respectively were 27.5+/-5, 67.7+/-7, 27.7+/-4 and 51.4+/-7 in group I versus 27.8+/-4, 67.5+/-6, 27.5+/-5 and 51.2+/-6 in group II. In group I, mitral valve repair was performed in 43 patients (88%) and replacement in six (12%). RESULTS: Preoperative data analysis showed no difference between groups. Five patients (10%) died in group I, compared with six (12%) in group II (p = NS). Within six months of surgery, LV function and geometry improved significantly in group I versus group II (LVEF, p <0.001; LVEDD, p = 0.002; LVESD, p = 0.003, LVEDP, p <0.001); only mild improvements were seen in group II. The regurgitation fraction decreased significantly in group I patients after surgery (p <0.001). Cardiac index increased significantly in groups I and II (p <0.001 and p = 0.03, respectively). In group I at follow up, four of six patients undergoing mitral valve replacement died, compared with five of 43 patients (11.5%) undergoing mitral valve repair (p = 0.007). At three years, the overall survival in group II was significantly lower than in group I (p <0.009). CONCLUSION: Both MV repair and replacement preserving subvalvular apparatus in patients with impaired LV function offered acceptable outcome in terms of morbidity and survival. Surgical correction of grade II-III MVR in patients with impaired LV function should be taken into consideration as it provides better survival and improves LV function. PMID- 11767183 TI - Impact of atrial fibrillation on clinical status, atrial size and hemodynamics in patients after mitral valve replacement. AB - BACKGROUND AND AIM OF THE STUDY: The association between mitral valve disease and atrial fibrillation (AF) is well known, but few data exist regarding the impact of AF after mitral valve replacement (MVR) on NYHA functional class, atrial size and hemodynamic parameters. The present study was conducted to evaluate these issues. METHODS: Eighty-six patients (26 men, 60 women) who underwent MVR were evaluated by transthoracic echocardiography. Fifty-nine patients had chronic AF (AF group), and 27 were in sinus rhythm (sinus group). Variables analyzed included end-systolic left atrial and right atrial areas, tricuspid regurgitation, and presence and duration of AF. Peak and mean transprosthetic mitral valve gradients and pulmonary pressure were estimated by Doppler echocardiography. RESULTS: Groups were matched for age, sex and time from MVR (mean 6.6 years). Sixty-four patients (77%) had rheumatic heart disease, 18 (21%) had mitral valve disease, and two (2%) had mitral valve prolapse. Mean duration of AF was 11+/-12 years (range: 8-50 years). Preoperatively, AF patients had a worse NYHA class than sinus patients (2.8+/-0.8 versus 1.1+/-0.7, p = 0.001), but both had similar fractional shortening of the left ventricle and preserved prosthetic mitral valve function. Multivariate analysis identified AF as a single predictor of NYHA class after MVR. Although left and right atrial areas were larger in AF patients (47+/-25 versus 27+/-7 cm2, p = 0.0001 and 30+/-12 versus 17+/-5 cm2, p = 0.0001, respectively), the left:right atrial size ratio was not significantly different between groups. Multivariate analysis identified mean transmitral gradient and duration of AF as independent predictors of left atrial size after MVR (p = 0.01 and p = 0.0001, respectively). Tricuspid regurgitation and duration of AF were independent predictors of right atrial size (p = 0.003 and p = 0.0001, respectively). CONCLUSION: The presence of AF after MVR is associated with a worse NYHA functional class, increased transmitral gradients, and larger areas of both atria, when compared with sinus rhythm. Hence, a special effort should be made to correct arrhythmia during surgery, and in case of paroxysmal arrhythmia, earlier surgery should be considered before the condition becomes chronic. PMID- 11767184 TI - Three-dimensional in-vivo dimensions of 'He's triangle' during acute left ventricular ischemia. AB - BACKGROUND AND AIM OF THE STUDY: Changes in the dimensions of 'He's triangle' (formed by mitral leaflet segments subtending two associated chordae tendineae) derived from data obtained in in-vitro mitral valve models have been proposed to provide a mechanistic explanation for mitral leaflet malcoaptation. The in-vivo dynamics of He's triangle, however, have not been hitherto determined. METHODS: Radio-opaque markers were placed in 13 sheep to delineate the mitral annulus and four (of an infinite number of possible) He's triangles formed by: (i) the anterior mitral leaflet (AML), first- (CT1) and second-order (CT2) chordae tendineae emanating from the anterior papillary tip (APT1) as well as from the posterior papillary tip (PPT1), respectively; and (ii) the posterior mitral leaflet (PML), CT1 and CT2 emanating from other loci on the anterior as well as the posterior papillary tips (APT2 and PPT2), respectively. Immediately postoperatively (anesthetized, open-chest), three-dimensional end-systolic marker positions were measured before and during circumflex coronary artery occlusion sufficient to produce mitral regurgitation, as verified by echocardiography. RESULTS: During ischemia, three leaflet segments constituting one side of three He's triangles elongated: The AML attached to APT1 and to PPT1 by 1.5+/-1.2 mm (p <0.001) and 1.3+/-0.8 mm (p <0.001), respectively, and the posterior leaflet attached to APT2 by 1.4+/-1.9 mm (p = 0.02). Apart from a 0.9+/-1.1 mm (p = 0.02) increase in the length of CT2 attached to APT2, the length of the seven other CT1 and CT2 remained relatively unchanged during acute left ventricular ischemia. CONCLUSION: With acute posterolateral ischemia, the lengths of CT1 and CT2 remained relatively constant, but the AML and PML lengths were not constant as the AML and PML 'unfurled' during acute left ventricular ischemia. These geometric changes may provide further insight into the mechanisms of acute ischemic mitral regurgitation, though it is not clear how they will be clinically helpful. PMID- 11767185 TI - Accessory mitral valve tissue causing left ventricular outflow tract obstruction: case reports and literature review. AB - Accessory mitral valve (AMV) tissue is a rare congenital malformation causing left ventricular outflow tract obstruction (LVOTO). We present three patients with AMV tissue undergoing surgery. A 60-year old man presented with an AMV leaflet, mild LVOTO and coronary artery disease and underwent accessory leaflet excision and coronary revascularization. A 24-year old man presented with an AMV leaflet, LVOTO and interatrial septal defect and underwent defect closure and accessory leaflet resection. An 8-month-old girl underwent interventricular septal closure and AMV leaflet resection but died on postoperative day 5 from progressive heart failure. Another 87 cases with AMV tissue were identified in the literature The anomaly was classified as: Type I (fixed: A = nodular, B = Membranous), and type II (mobile: A = pedunculated, B = leaflet like). Type IIB was further subdivided as rudimentary chordae and developed chordae. Patients with AMV tissue causing LVOTO may undergo mass removal with acceptable postoperative outcome. Prophylactic removal of AMV tissue should not be attempted in patients with no or mild LVOTO and no other associated heart defects. These patients should be followed and observed periodically by Doppler echocardiography to identify any progression in LVOTO. PMID- 11767186 TI - Aortic valve preservation in acute type A dissection: mid-term results. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the long-term effectiveness of a strategy for managing the aortic valve, aortic root and ascending aorta according to the pathology in acute aortic type A dissection. Results after surgery for acute type A dissection with preservation of the aortic valve were reviewed. METHODS: The patient group included 57 hospital survivors operated on according to a surgical strategy of aortic valve resuspension and supracoronary ascending aortic graft implantation. Reinforcement of the aortic stumps with gelatin-resorcinol-formaldehyde glue was performed in all patients. Aortic valve function in all survivors was investigated by echocardiographic follow up at 30 days, 6 and 12 months after surgery, and yearly thereafter. RESULTS: During the follow up period, nine patients (16%) died without reoperation. Actuarial probability of freedom from reoperation for aortic valve failure in the complete series was estimated as 100% after both 30 days and 12 months. Postoperatively, one patient underwent reoperation 14 months for aortic regurgitation, and three patients for aortic regurgitation with sinus of Valsalva dilatation between 48 and 88 months. The hospital mortality rate at reoperation was 50% (n = 2). CONCLUSION: Valve-sparing surgery is possible and can be recommended for the majority of patients with acute type A aortic dissection. PMID- 11767187 TI - Traumatic aortic regurgitation: aortic valvuloplasty controlled by aortoscopy. AB - Traumatic aortic insufficiency is a rare occurrence after blunt chest trauma, and requires surgical treatment. Aortic valve replacement has been proposed as the procedure of choice, but primary valve repair is being performed increasingly more often. In a plead for conservative surgery, we report a case of valvuloplasty that was controlled by intraoperative aortic endoscopy. When operative conditions permit aortic valve repair, this should be carried out in order to avoid aortic valve replacement and its potential complications, especially in young patients with healthy valves. Replacement is the safest treatment for complex or multiple injuries of the aortic valve, however. PMID- 11767188 TI - Long-term results with the Xenomedica porcine bioprosthesis in the mitral position. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate our clinical experience with the Xenomedica heart valve prosthesis, a low-pressure glutaraldehyde-preserved porcine aortic valve with low-profile mounting. METHODS: Between January 1983 and July 1990, 242 consecutive patients (75 men, 167 women; mean age 59.8+/-8.0 years; range: 32-77 years) underwent mitral valve replacement with the Xenomedica prosthesis. Preoperatively, patients were in NYHA classes III (66%) and IV (26%); 94 patients (39%) had undergone previous cardiac surgery and 201 (83%) had chronic atrial fibrillation. Etiology was rheumatic in 51%, myxomatous in 7%, ischemic in 1%, endocarditis in 2%, and due to dysfunction of a previously implanted device in 39%. In total, 115 (47%) patients underwent an associated procedure. Mean follow up was 142+/-24 months (range: 2-181 months); total follow up was 2,627 patient-years. RESULTS: Early mortality was 8.2% (14 patients with low-output syndrome, three with multi-organ failure, one with stroke and two with major bleeding, 2). Late mortality was 45% (3.8%/pt-year) (84 cardiac deaths, 38 being valve-related). Actuarial survival at 5, 10 and 15 years was 69+/-3%, 52+/-3% and 38+/-4%, respectively. Actuarial estimates of freedom from structural valve deterioration (SVD) at 5, 10 and 15 years were 93+/-2%, 64+/-4%, and 25+/-9%; in almost all cases SVD occurred in progressive fashion. At 5, 10 and 15 years, estimates of freedom from thromboembolism were respectively 90+/-2%, 83+/-3% and 83+/-3%, for anticoagulant-related hemorrhage 96+/-1%, 88+/ 3% and 88+/-3%, for endocarditis 96+/-1%, 94+/-2% and 94+/-2%, and for reoperation 93+/-2%, 67+/-4% and 54+/-6%. Estimates of freedom from all valve related mortality at 5, 10 and 15 years were 87+/-2%, 80+/-3% and 75+/-4%. Multivariate analysis (Cox model) showed younger age to be a significant risk factor for reoperation. CONCLUSION: Long-term results with the Xenomedica device implanted in the mitral position appear in line with those achieved for other first-generation bioprostheses. However, incidence of primary tissue failure within 10 years was unsatisfactory. Although sudden dysfunction of the device never occurred, close monitoring of survivors is warranted. PMID- 11767189 TI - Evaluation of valve-related complications in patients with Sorin Bicarbon prosthesis: a seven-year experience. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the medium-term results of aortic valve replacement (AVR), mitral valve replacement (MVR) and double valve replacement (DVR) with the Sorin Bicarbon prosthesis. METHODS: A total of 990 patients (568 men, 422 women; mean age 60+/-10 years; range: 20-86 years) was reviewed who received 1,108 Sorin Bicarbon prostheses between 1992 and 1998 at three institutions. AVR was performed in 541 patients (55%), MVR in 330 (33%) and DVR in 119 (12%). Concomitant procedures, mainly coronary artery grafting, were performed in 222 patients (22%). Follow up was 98% complete; total cumulative follow up was 3,091 patient-years. RESULTS: Hospital mortality was 3.7% (n = 37). There were 49 late deaths; actuarial survival at seven years was 88+/-2% after AVR, 86+/-5% after MVR, and 78+/-8% after DVR. At last follow up, 915 survivors were in NYHA functional class I or II. At seven years, actuarial freedom from valve-related deaths, valve thrombosis, embolism and bleeding respectively was 96+/-1%, 99+/-1%, 93+/-2% and 91+/-3% after AVR; 97+/-2%, 97+/ 3%, 90+/-3% and 86+/-7% after MVR; and 92+/-6%, 98+/-1%, 64+/-2% and 82+/-2% after DVR. Reoperation was required in 20 patients (due to valve thrombosis in six, endocarditis in five and periprosthetic leak in nine). At seven years, actuarial freedom from reoperation was 97+/-1%, 96+/-2% and 84+/-9% after AVR, MVR and DVR, respectively; actuarial freedom from endocarditis was 99+/-1%, 99+/ 1% and 95+/-5%. Nine patients experienced a nonstructural valve dysfunction (all periprosthetic leak), while no cases of structural failure were observed. CONCLUSION: The Sorin Bicarbon prosthesis has shown good medium-term results with regard to clinical improvement, and low incidence of valve-related complications. Thus, it appears to be a reliable valve substitute when the use of a mechanical prosthesis is indicated. PMID- 11767190 TI - Comparative hydrodynamic evaluation of bioprosthetic heart valves. AB - BACKGROUND AND AIM OF STUDY: Pressure gradients across cardiac valve prostheses have been identified as one of the most important performance measures in valve replacement surgery. Specifically in aortic valves, these gradients influence reduction of left ventricular hypertrophy and are postulated to influence long term survival. The correct choice of replacement valve is hampered by a lack of uniform measures of valve performance. The aim of this study was to compare in vitro hydrodynamic performance of commercially available bioprosthetic valves under identical test conditions. METHODS: In-vitro steady forward flow and pulsatile flow tests were performed on aortic and mitral bioprosthetic valves in accordance with ISO/FDA guidelines at two different institutions to obtain objective hemodynamic performance measures. Measurements were recorded at various flow rates, flow and pressure to obtain mean pressure gradients and effective orifice areas (EOAs). RESULTS: Wide variation in pressure gradients was found among tested valves of each size. For a given size, differences of 200 to 400% were observed; in general, the valve models' relative rankings in pressure drop were independent of size. CONCLUSION: The Carpentier-Edwards Perimount valve showed superior performance at all sizes tested. While the mean pressure gradients and EOAs reported by each institution differed for a given valve, the performance of valve models relative to each other was similar. The testing of valves under identical conditions is a valuable comparative indicator of valve hemodynamic performance. PMID- 11767191 TI - Long-term results of pulmonary balloon valvulotomy in adult patients. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to define the long-term outcome of pulmonary balloon valvulotomy (PBV) in adult patients. METHODS: PBV was performed in 87 patients (46 females, 41 males; mean age 23+/-9 years; range: 15-54 years) with congenital pulmonary valve stenosis (PS). Intermediate follow up catheterization (mean 14.6+/-5.0; range: 6-24 months) was performed after PBV in 53 patients. Clinical and Doppler echocardiography examinations were carried out annually in 82 patients (mean 8.0+/-3.9; range: 2-15 years). RESULTS: There were no immediate or late deaths. The mean catheter peak pulmonary gradient (PG) before and immediately after PBV, and at intermediate follow up was 105+/-39, 34+/-26 (p <0.0001) and 17+/-14 (p <0.0001) mmHg, respectively. The corresponding values for right ventricular (RV) pressure were 125+/-38, 59+/-21 (p <0.0001) and 42+/-12 (p <0.0001) mmHg, respectively. The infundibular gradients immediately after PBV and at intermediate follow up were 31+/-23 and 14+/-9 mmHg (p <0.0001), whilst cardiac index improved from 2.68+/-0.73 to 3.1+/-0.4 l/min/m2 (p <0.05) at intermediate follow up. Doppler PG before PBV and at intermediate and long-term follow up were 91+/-33 (range 36-200) mmHg, 28+/-12 (range 10-60) mmHg (p <0.0001) and 26+/-11 mmHg (p = 0.2), respectively. New pulmonary regurgitation (PR) was noted in 21 patients (25%) after PBV. Five patients (6%) with a suboptimal result (immediate valve gradient > or =30 mmHg) developed restenosis and underwent repeat valvulotomy 6-12 months later using a larger balloon, and with satisfactory outcome. Moderate to severe tricuspid regurgitation (TR) in seven patients regressed after PBV. CONCLUSION: The long-term results of PBV in adults are excellent, with regression of concomitant, severe infundibular stenosis and/or severe TR. Hence, PBV should be considered as the treatment of choice for adult patients with PS. PMID- 11767192 TI - Percutaneous transvenous mitral commissurotomy in a patient with prosthetic aortic valve. AB - Patients with rheumatic valvular heart disease who have undergone valve surgery may present later with progression of disease in other valves. We report a case of successful percutaneous transvenous mitral commissurotomy (PTMC) in a 58-year old male who underwent aortic valve replacement (AVR) with a No. 23 Bjork-Shiley valve for severe rheumatic aortic regurgitation in 1982. At AVR, echocardiography revealed mild mitral stenosis (MS) and mitral valve area (MVA) 2.5 cm2. Over 18 years, the mitral valve disease progressed to severe MS and the patient presented with class III exertional dyspnea. He underwent successful PTMC (Inoue balloon technique). Post-procedure echocardiography revealed a MVA of 2.0cm2 and grade II mitral regurgitation. Anticoagulation management, infective endocarditis prophylaxis and procedural modifications are discussed. PMID- 11767193 TI - Influence of 5-hydroxytryptamine on aortic valve competence in vitro. AB - BACKGROUND AND AIM OF THE STUDY: The contraction of cusp tissue has been implicated to play a role in aortic valve function. The effect of the contractile agent 5-hydroxytryptamine (5-HT) on the competence of isolated aortic roots has been assessed, and the vasomotor properties of 5-HT on aortic root tissue examined. METHODS: Isolated porcine aortic roots were pressurized with Kreb's solution through the aortic arch. 5-HT was added in increasing concentrations (10(-7) to 10(-5) M) and the degree of leakage measured over time. In additional experiments, portions of sinotubular junction, sinus, annular and cusp tissue were set up in organ baths, placed under tension, and challenged with 5-HT (10( 9) to 10(-5) M). Viability of each valve structure was assessed by addition of KCl (90 mM). RESULTS: The rate of leakage from intact aortic roots increased when 10(-6) and 10(-5) M 5-HT was added. The maximum effect, observed at 10(-5) M 5 HT, was equal to an increase of 61.8+/-23.0% above control (p <0.05). The perfusion pressure at each concentration of 5-HT was unchanged. This response was inhibited by the 5-HT2A receptor antagonist ketanserin. Addition of KCl to isolated valve structures gave a mean contractile response of 0.8+/-0.1mN for cusp, 19+/-11.0 mN for annular, 29+/-8.0 mN for sinus, and 23+/-8.0 mN for sinotubular junction tissue (each n = 4). Only cusp tissue contracted when treated with 5-HT, with a maximum 105.5+/-17.2% (n = 4) of the response to KCl. The response to 5-HT was blocked by the 5-HT2A-receptor antagonist ketanserin at 10(-6) M (n = 4). None of the other aortic root structures responded to 5-HT. CONCLUSION: These results show that 5-HT influences the competence of isolated porcine aortic valves. This effect is contributed by contraction of the cusp tissue, and is mediated by 5-HT2A receptors. These effects may contribute to the association between valve dysfunction, 5-HT and certain appetite suppressants. PMID- 11767194 TI - Cell proliferation in carcinoid valve disease: a mechanism for serotonin effects. AB - BACKGROUND AND AIM OF THE STUDY: Elevated serum serotonin is associated with carcinoid heart disease, the hallmark of which is valvular thickening. Yet, the mechanistic role of serotonin in carcinoid heart disease is poorly understood. We postulated that serotonin has a direct mitogenic effect on cardiac valvular subendocardial cells, and that this effect is mediated by serotonin receptors. METHODS: The dose-dependent proliferative effects of serotonin (10(-8) to 10( 4)M) on cultured porcine aortic valve cells via a [3H]thymidine assay were determined in vitro. Serotonin receptor antagonist studies in culture were also performed using methiotepin, a 5HT1b antagonist, and ketanserin, a 5HT2 receptor antagonist, to determine the mechanism of serotonin action. The ex-vivo proliferation level in human carcinoid (n = 26) and normal valves (n = 10) was compared using proliferating cell nuclear antigen (PCNA) staining, a marker for proliferation. Identification and localization of specific 5HT receptor was assessed by immunostaining for serotonin receptors in the valves. RESULTS: Serotonin increased valvular proliferation in vitro in a dose-dependent manner (10-fold increase) (p <0.001), and this mitogenic effect was inhibited by methiotepin but not ketanserin. In human carcinoid heart valves the level of proliferation was 35-fold higher than in normal human valves (p <0.001). 5HT1b receptors were found only in the carcinoid valves, and not in the normal valves. CONCLUSION: Serotonin is a powerful mitogen for valvular subendocardial cells. The mitogenic effect is at least partly mediated via 5HT1b receptors. Subendothelial cell proliferation is significantly elevated in human carcinoid valves in vivo. The data suggest a mechanism whereby serotonin may contribute to valvular proliferation in carcinoid heart disease. PMID- 11767195 TI - Hypersensitivity to warfarin in a patient with a mechanical aortic prosthesis. AB - The case of a patient with a prosthetic aortic valve and warfarin hypersensitivity is presented. On rechallenging the patient with warfarin, a spongiotic dermatitis with heavy superficial perivascular lymphocytic infiltrates with eosinophils was seen. The patient was finally discharged on aspirin therapy alone and is doing well to date. Warfarin hypersensitivity is rare, and only incidental reports exist regarding its incidence and management. It is conceivable that newer antiplatelet agents, whether alone or in combination with aspirin, will provide better control of thromboembolic events in patients with warfarin intolerance. PMID- 11767196 TI - Localization of collagen type IV, fibronectin and elastin in the flexor digitorum tendons and in the perichondrium during prenatal development of the human hand. AB - The distribution of collagen type IV, fibronectin and elastin in the flexor digitorum tendons and in the perichondrium of staged human embryos and fetal hand (from 6 to 12 weeks of gestation) has been studied to analyse the immunohistochemical features of the human hand during the first trimester of pregnancy. At 6 weeks in the transverse sections of the fingers there is no evidence of the presence of collagen type IV and elastin which remain absent even in the controls of 9, 11 and 12 weeks. On the contrary from 6 weeks of intrauterine life the fibronectin is widely distributed with thickening above all in the perichondrium and in the subjacent portion of the cartilaginous model of the bone. At 9 weeks a high positivity is detected not only along the perichondrium but even into the extra-cellular matrix of every mesenchymal cell. At 11 and 12 weeks the perichondrium is always positive but a high positivity is now present along the flexor tendons and their related sheaths that show a high grade of differentiation. To sum up, the absence of the collagen type IV into the flexor and extensor tendons is understandable because it isn't a fibrillar collagen. More difficult is to understand the absence of the elastin (component of the mature tendons) until the 12th week. On the contrary the presence of the fibronectin, a structural glycoprotein, proof of active morphogenesis of mesenchvmal cells, earlier in the perichondrium and cartilaginous sketch and later in the flexor tendons and their sheaths indicates that probably among the cells of mesenchymal origin the perichondrium with the cartilaginous model of the bone come before and perhaps orient the differentiation of the other components of the human hand. PMID- 11767197 TI - Macroscopic anatomy of the superficial veins of the lower limb: a systematic review based upon echography. AB - Saphenous Veins are described in Anatomy textbooks as superficial veins running in the amorphous fatty layer of the lower limbs. Recent papers have demonstrated the complex fascial relationship of Saphenous Veins with the connective framework of the lower limb hypodermis. The aim of the present paper was to systematically review the anatomy of lower limb superficial veins, based upon echographic findings, in a series of normal subject. Our results offer new insight into lower limbs superficial veins anatomy, with important clinical and surgical implications. PMID- 11767198 TI - A comparison between the heart of young athletes and of young healthy sedentary subjects: a morphometric and morpho-functional study by echo-color-doppler method. AB - Morphologic and morpho-functional heart differences between healthy young athletes and healthy young subjects who do not practice agonistic sport have been studied using Color Doppler Echography (CDE). Overall, 68 subjects were enrolled in the study (age range: 19-26 yrs). Of them, 34 subjects (17 men and 17 women) were practicing sport agonistically; the 34 controls (17 men and 17 women) did not practice any sport on a regular basis. In each subject, age, height, weight, body mass index, practiced sport, systolic and diastolic blood pressure were recorded. CDE measures included telediastolic left and right ventricular diameters (LVDd and RVDd, respectively), interventricular septum thickness (IVSd), posterior wall thickness of the left ventricle (PLVWd), left and right atrium diameters during ventricular systole (LAD and RAD respectively), and continence of each heart valve (mitral; tricuspid; aortic; pulmonic). In women, LADd was significantly higher in the athletes than in the controls (35.04+/-4.13 vs 31.81+/-3.34; p<0.02). Physiological regurgitation in at least one heart valve was observed in 15 out of 17 (88.2%) of the athletes; in 12 cases only one valve was involved: the mitral valve presented physiological regurgitation in 8 women, the tricuspid in 4, the aortic in 2 and the pulmonic in 6. In the control female population (17 persons), only 2 women showed evidence of regurgitation. In men, except for RVDd, CDE measurements were all significantly higher in the athletes than in the controls: LVDd (49.4+/-3.13 vs 46.02+/-4.46; p<0.02); IVSd (9.79+/ 1.24 vs 8.59+/-0.91; p<0.003); PLVWd (8.63+/-1.29 vs 7.48+/-0.66; p<0.002). Physiological regurgitation through one or more heart valves was demonstrated in all the 17 male athletes studied; in 9 cases (52.9%) only one valve was involved. Mitral regurgitation was ob- served in 8 cases (47%); tricuspid in 6 (35.3%). No physiological regurgitation through the aortic valve was found, while 15 cases (88.2%) presented a pulmonic regurgitation. Among male controls, physiological regurgitation was demonstrated only in 2 persons out of 17 (11.8%), both involving the pulmonic and the aortic valve. In the total population of athletes compared to controls, analyzing men and women jointly, we found that LAD (p<0.001),RAD (p<0.001), LIVD (p<0.01) were significantly larger in cases than in controls, while for RVD, IVSd and PLVWd such a difference did not reach statistical significance. No relationship was fouhd between CDE data and either age, height, weight or blood pressure. PMID- 11767199 TI - Descriptive and morphometric anatomy of the architectural framework of microcirculation: a Videocapillaroscopic study on healthy adult subjects. AB - Conventional Capillaroscopy allows the observation of a limited number of areas, classically the fingernail-fold. Videocapillaroscopy, on the contrary, can be performed on any part of the skin and of clinically accessible mucosae. The aim of the present paper was to investigate the architectural frameworks of microcirculation in the various regions of the body and their morphometric parameters in healthy adult subjects. Our findings showed four basic architectural patterns plus two special patterns. The calibre of capillary loops ranged from 15 to 20 micrometers, and capillary density ranged from 14 to 30 capillary loops each square millimetre. These findings might be used as normal reference data for future studies. PMID- 11767200 TI - Morphological aspects of an artificial skin. AB - Culture technology have permitted the generation of an artificial skin using human neonatal stem cells. A major advantage of this model is that epithelial mesenchymal interactions are maintained. We have studied some morphological aspects concerning tissue organisation and cell differentiation using immunohistochemistry and electron microscopy. The epidermal equivalent was composed by a stratified and keratinized epithelium. The cells of this epithelium were cytokeratin-positive and disposed in different layers corresponding to natural skin, i.e. basal, spinous, granular and keratinized layers. The ultrastructural aspects concerning keratinocyte differentiation were comparable to natural epidermis. The dermal equivalent was composed by a loose connective tissue. The cells of the dermal equivalent were vimentin-positive and belonged to the fibroblast lineage. Although poorly developed, a basement membrane was detectable in the dermo-epidermal junction. The organ architecture and the high level of cell differentiation suggest that this bioengineered skin might be considered a useful substitute for natural skin in clinical, biological and pharmacological applications. PMID- 11767201 TI - Further considerations on the intranuclear distribution of HMGI/Y proteins. AB - We have investigated the intranuclear distribution of High-mobility group proteins I/Y by means of immunofluorescent staining employing a variety of cell lines. Confocal scanning laser microscopy analysis revealed that High-mobility group proteins I/Y are present in an intranuclear fibrogranular network and mitotic chromosomes. In Caski, C4I, Flow 2002, and K562 cell lines, High-mobility group proteins I/Y were absent from nucleoli, whereas in HeLa cells they were present in this nuclear domain. Double immunolabeling studies showed that High mobility group proteins I/Y co-localize with other key nuclear components such as NuMA, SC-35, and TAF(II)70. Nuclear reactivity for High-mobility group proteins I/Y dramatically decreased in apoptotic nuclei of HL-60 human leukemia cells. Our morphological data correlate well with previous biochemical and functional findings obtained by other investigators, who have demonstrated multiple roles for this class of polypeptides. However, they point to the likelihood that High mobility group proteins I/Y are involved in as yet unidentified functions, most likely in the speckle domains of the nucleus. They also show that conceivably these proteins are also involved in apoptosis. PMID- 11767203 TI - Rich dynamics of a ratio-dependent one-prey two-predators model. AB - The objective of this paper is to systematically study the qualitative properties of a ratio-dependent one-prey two-predator model. We show that the dynamics outcome of the interactions are very sensitive to parameter values and initial data. Specifically, we show the interactions can lead to all the following possible outcomes: 1). competitive exclusion; 2). total extinction, i.e., collapse of the whole system; 3). coexistence in the form of positive steady state; 4). coexistence in the form of oscillatory solutions; and 5). introducing a friendly and better competitor can save a otherwise doomed prey species. These results reveal far richer dynamics compared to similar prey dependent models. Biological implications of these results are discussed. PMID- 11767202 TI - Morphological features and measurements in a human fetus with karyotype 69, XXX: comparison with fetuses of the same CRL, without chromosomal anomalies. AB - A triploid fetus (karyotype 69, XXX) with crown-rump length (CRL) 94 mm, presenting micro- and retrognathia, low-set ears and crooked feet, was cleared and double-stained with alizarin red S and alcian blue for detecting the ossification patterns in the vertebral column, ribs, ischium, limbs, and face. Longitudinal measurements of some long bones in the upper (humerus, ulna, radius) and lower (femur, tibia, fibula) limb were taken. The values of both the total length (TL) and the ossified part (OL) of each long bone, as well as the OL/TL per cent ratio were considered. Reference points were located on the mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN), gonion (GO), superior symphyseal point (SSP) for measuring linear dimensions. Since the aim of this work was to assess the influence of triploidy 69, XXX the skeletal development and growth patterns, all values obtained in the examined specimen were related with those relative to a group of fetuses, without any detectable malformation and chromosomal anomalies, with a CRL mean value of 93 mm. Results evidenced that the triploid fetus presented growth restriction and that the vertebral centra ossification and the mandibular development were much delayed with the normal ossification patterns. PMID- 11767204 TI - Coalescence time for two genes from a subdivided population. AB - In this paper a new form of the solution for the Laplace transform and moments of the distribution of the waiting time for two genes to coalescence is presented. The two genes are sampled from a subdivided population where migration rates between populations are constant in time. Equal subpopulation size is not assumed. For the special case of an island model with equal migration rates between islands, the Laplace transform of the coalescence time and the first and second moments are found explicitly. The new form of the solutions allows numerical calculation. The connection of how the results relate to a panmictic population when migration rates are large is illustrated using strong-migration limit theory. PMID- 11767205 TI - Pattern formation in discrete cell lattices. AB - In recent years, models for lattices of discrete cells have been attracting increased attention due to their greater flexibility to represent signalling and contact-dependent cell-cell interaction than conventional reaction-diffusion models. Using the almost forgotten method of Othmer and Scriven (1971) to calculate eigenvalues and eigenvectors for the Jacobian of the homogeneous state, a Turing-like linear stability analysis is carried out for diffusion-driven (DD) and signalling-driven (SD) discrete models. The method is a generalisation of the original method of Turing (1952). For two-species models it is found that there are profound differences between the two types of model when the size of the lattice increases. For DD models, the homogeneous state is typically either always stable, always unstable, or becomes unstable when the lattice gets suffficiently large. For SD models, the homogeneous state is typically unstable independent of lattice size, and stable only in a minor part of parameter space. Thus, SD models seem in general more pattern-prone than DD models. The conjecture that the linear analysis predicts the final pattern is investigated for a DD system with Thomas internal dynamics. Commonly the final pattern resembles the pattern of the initial perturbation of the homogeneous state, but this is by no means a general feature. When applied to a recent model for Delta-Notch lateral inhibition, linear analysis must be supplemented by various non-linear techniques to get a deeper insight into the patterning mechanisms. The overall conclusion is that a linear Turing analysis may be useful for predicting pattern, but when it comes to explaining patterns, non-linear analysis cannot be ignored. PMID- 11767206 TI - Transient dynamics and early diagnostics in infectious disease. AB - To date, mathematical models of the dynamics of infectious disease have consistently focused on understanding the long-term behavior of the interacting components, where the steady state solutions are paramount. However for most acute infections, the longterm behavior of the pathogen population is of little importance to the host and population health. We introduce the notion of transient pathology, where the short-term dynamics of interaction between the immune system and pathogens is the principal focus. We identify the amplifying effect of the absence of a fully operative immune system on the pathogenesis of the initial inoculum, and its implication for the acute severity of the infection. We then formalize the underlying dynamics, and derive two measures of transient pathogenicity: the peak of infection (maximum pathogenic load) and the time to peak of infection, both crucial to understanding the early dynamics of infection and its consequences for early intervention. PMID- 11767207 TI - Influence of dietary protein levels on beta-alanine aminotransferase expression and activity in rats. AB - beta-Alanine-oxoglutarate aminotransferase (beta-AlaAT I) and beta-alanine pyruvate aminotransferase (beta-AlaAT II) catalyze the transamination reaction of omega-amino acids such as beta-alanine, beta-aminoisobutyrate, and gamma aminobutyrate, amino acids that are not protein constituents. The influence of dietary protein levels on the expression and activities of these enzymes was investigated by using male rats. Both beta-AlaAT I and beta-AlaAT II activities in the liver were increased with the level of protein in the diet in accordance with changes in their mRNA levels. However, the beta-AlaAT I activity in the kidney was increased by protein-free and low-protein diets in relation to changes in its mRNA level. On the other hand, the level of beta-AlaAT II activity in the kidney was slightly decreased by a protein-free diet. Neither beta-AlaAT I nor beta-AlaAT II activities in the kidney were affected by a high-protein diet. These results suggested that beta-alanine may be used efficiently in animals fed a proteinfree or low-protein diet because the kidney provides beta-alanine by means of the hydrolysis of beta-alanyl-L-histidine (carnosine). The addition of beta-alanine to the diet significantly activated beta-AlaAT I in the kidneys of rats in accordance with changes in its mRNA level. In the rat brain, beta-AlaAT I activity was not altered by the dietary protein level or by the beta-alanine diet, and beta-AlaAT II activity was not detected. PMID- 11767208 TI - Effects of soy protein on levels of remnant-like particles cholesterol and vitamin E in healthy men. AB - We determined the effects of soy protein isolate (SPI) intake on remnant-like particles (RLP), lipolytic enzymes, lipid transfer protein, transaminases, sex hormones, iron, calcium, and vitamin E in healthy men. In the first randomized, crossover experiment, 14 men were given either 20 g per day of SPI or nothing (control) for each 4-week segment. After 3 weeks of SPI intake, TG and RLP cholesterol levels were significantly lower than the baseline by 13.4% (p<0.05) and 9.8% (p<0.05), respectively. However, no significant change was found in total and low-density lipoprotein (LDL) cholesterol levels or the activities of lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase. Although the levels of transaminases. testosterone, iron, and calcium did not change, the vitamin E level was reduced from the baseline by 9.7%, a significant decrease (p<0.01). In the second study, we attempted to determine the effect of vitamin E supplement taken with SPI. For each 3-week segment, 12 men were given 20 g per day of SPI, either with or without 200 mg per day of vitamin E, in a randomized crossover design. The vitamin E level was reduced by 9.2%, a significant decrease (p<0.05), after SPI intake for 3 weeks, and vitamin E supplement increased vitamin E level significantly (p<0.05). These results demonstrate that SPI intake reduces remnant lipoproteins, TG, and the plasma level of vitamin E, although vitamin E supplementation compensates for the reduction of vitamin E. Therefore the supplementation of vitamin E may be required in subjects with long-term and abundant intake of soy protein. PMID- 11767209 TI - Association between current nutrient intakes and bone mineral density at calcaneus in pre- and postmenopausal Japanese women. AB - The association between nutrient intake and bone mineral density (BMD) at calcaneus was cross-sectionally examined in 243 pre- (aged 29-60 years) and 137 postmenopausal (aged 39-60 years) Japanese women who participated in a BMD checkup and have kept a stable diet for at least 3 previous years and had no dietary therapy. Nutrient intakes were assessed with a self-administered diet history questionnaire. BMD at calcaneus was measured with dual-energy X-ray absorptiometry. In a multiple regression analysis with adjustments for nondietary factors such as age, body height, fat body weight, nonfat body weight, and number of deliveries, calcium (p<0.01) and niacin (p<0.05) significantly and positively, and phosphorus and dietary fiber (p<0.05 for both) significantly and negatively correlated in premenopausal women, and only potassium (p<0.05) significantly and positively correlated in postmenopausal women with BMD. The results suggest that several nutrients correlate with BMD, and the associations differ depending on menopausal status. epidemiology, diet, nutrients, bone mineral density. Japanese women PMID- 11767210 TI - CH-19 sweet, nonpungent cultivar of red pepper, increased body temperature in mice with vanilloid receptors stimulation by capsiate. AB - We investigated the effect of CH-19 Sweet, a nonpungent cultivar of red pepper, and capsiate, a nonpungent capsaicin analog found in CH-19 Sweet on body temperature in mice. The body temperature was recorded from conscious and unrestrained mice by use of a telemetry system. The body temperature in the mice administered CH-19 Sweet was higher than in the mice administered California Wandar, which contains no capsiate or capsaicin. The body temperature in the mice administered capsiate was higher than in the mice administered the vehicle. Furthermore, we injected capsazepine, a specific antagonist of vanilloid receptors, into the peritoneal cavity and orally administered capsiate via a stomach tube to mice. The body temperature in the mice pretreated with capsazepine was lower than in the mice injected with the vehicle. This result suggested that capsazepine suppressed the rise in body temperature induced by capsiate administration. In conclusion, CH-19 Sweet increased body temperature, and this effect may be induced by the vanilloid receptors' stimulation of capsiate. PMID- 11767211 TI - Beneficial effect of dietary wheat glycolipids on cecum short-chain fatty acid and secondary bile acid profiles in mice. AB - In the present study, to explore the beneficial effect of dietary galactoglycerolipids on the lower digestive tract environment, male BALB/c mice were fed a 5% wheat glycolipid, fiber-free diet, or the standard AIN diet for 3 wk. The wheat glycolipid composition was digalactosyldiacylglycerol 51.6%, ceramide monohexoside 6.6%, acylated sterylglucoside 3.4%, and other lipids 22.2%, (mostly phospholipids). Cecum and colon weights and colonic crypt depth were significantly greater in the glycolipid-diet mice relative to groups fed the other two diets. Furthermore, in the cecum, propionate. butyrate, and total short chain fatty acids, concentrations were significantly greater in the glycolipid diet mice than others were, and correlated with the observed increased lower digestive tract (cecum and colon) weights and colonic crypt depth. The cecal lithocholic acid/deoxycholic acid ratio, a risk index for colorectal cancer, was significantly lower in the glycolipid-diet mice than in the other two dietary groups. These results suggest that the dietary supplementation of plant-source galactoglycerolipids may contribute to improving the lower digestive tract environment. PMID- 11767212 TI - Xanthurenic acid inhibits metal ion-induced lipid peroxidation and protects NADP isocitrate dehydrogenase from oxidative inactivation. AB - Vitamin B6 deficiency increases the lipid peroxidation and the synthesis of xanthurenic acid from tryptophan. Antioxidant properties of xanthurenic acid were examined in relation to the coordination of transition metals. Xanthurenic acid inhibited the formation of thiobarbituric acid-reactive substances as a marker of iron-mediated lipid peroxidation and copper-dependent oxidation of low density lipoprotein. NADP-isocitrate dehydrogenase (EC 1.1.1.42), a principal NADPH generating enzyme for the antioxidant defense system, was inactivated by reduced iron and copper, and xanthurenic acid protected the enzyme from the Fe2+-mediated inactivation. Xanthurenic acid may participate in the enhanced regeneration of reduced glutathione by stimulating the NADPH supply. Xanthurenic acid further enhanced the autooxidation of Fe2+ ion. Other tryptophan metabolites such as kynurenic acid and various quinoline compounds did not inhibit the lipid peroxidation and the inactivation of NADP-isocitrate dehydrogenase, and they showed little or no effect on the Fe2+ autooxidation. The antioxidant properties of xanthurenic acid are related to the metal-chelating activity and probably to the enhanced oxidation of reduced transition metals as a prooxidant, and this action may be due to the electron deficient nature of this compound. PMID- 11767213 TI - Time course of leucine-induced 4E-BP1 and S6K1 phosphorylation in the liver and skeletal muscle of rats. AB - The purpose of the current study was to assess the involvement of the branched chain amino acid leucine in the regulation of translation initiation in the liver and to compare the time course of leucine action on the translation initiation in the liver and skeletal muscle of rats. The phosphorylation of the eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1) frees eIF4E and stimulates protein synthesis by accelerating translation initiation. Phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K) is thought to be involved in regulating the synthesis of certain ribosomal proteins and other selected proteins with polypyrimidine clusters near the transcription start site. Food-deprived (18 h) male rats were orally administered 135 mg/100 g body weight L-leucine and sacrificed at 0, 1, 3, or 6 h after administration. The oral administration of leucine resulted in an enhanced phosphorylation of 4E-BP1 and S6K1 in both the liver and skeletal muscle. A time-dependent change in the phosphorylation state of 4E-BP1 and S6K1 was more acute in the skeletal muscle than in the liver and closely paralleled the changes in plasma leucine concentration. Our results indicate that the primary mediator in 4E-BP1 phosphorylation and S6K1 phosphorylation by the oral administration of leucine is an increase in the plasma concentration of leucine. Furthermore, our findings suggest differential sensitivity in the tissue response to oral administration of leucine. PMID- 11767214 TI - Reduction of dehydroerythorbic acid in vitamin C-deficient guinea pigs. AB - A reduction of dehydroerythorbic acid (DERA) to erythorbic acid (ERA) in vitamin C-deficient guinea pigs was evaluated and compared with that of dehydroascorbic acid (DASA). Thirty-six guinea pigs were fed with vitamin C-deficient diets for 18 days. On day 19, the guinea pigs were divided into four groups for the administration of 100 mg of DERA, ERA, ascorbic acid (ASA), or DASA every day. After 12 days of oral administration, the concentration of DERA, ERA, ASA, and DASA in the liver, adrenal, spleen, kidney, and plasma of guinea pigs was determined by HPLC. A recovery from scurvy was measured in terms of weight gain and serum alkaline phosphatase activity. All four groups showed similar recovery, indicating that the oral administration of relatively high concentrations of DERA reversed the effects of scurvy in vitamin C-deficient guinea pigs. In spite of DERA or DASA administration, ERA or ASA was mainly detected in the tissues. The reduction ratios of DEAR and DASA were similar (approximately 80%) in all tissues except spleen. These results suggest that both DASA and DERA are taken up and reduced to ASA or ERA in vivo. PMID- 11767215 TI - Emergency physicians and emergency medicine: an imminent need in India. PMID- 11767216 TI - The bone and joint decade 2000-2010: the Indian perspective. PMID- 11767217 TI - Gender, sexual abuse and risk behaviours in adolescents: a cross-sectional survey in schools in Goa. AB - BACKGROUND: There is little information on the prevalence and correlates of sexual abuse in adolescents in India. METHODS: A cross-sectional survey of all Class XI students in eight higher secondary schools in Goa (n = 811 ) was conducted in March 2000. A self-report questionnaire, developed and piloted in collaboration with the adolescents, elicited information on education, mental health, risk behaviours and the experience of violence and sexual abuse in the previous year. RESULTS: A third of adolescents had experienced some form of sexual abuse. Sexual abuse experiences were associated with the experience of other forms of physical and verbal violence. Coercive sex had been experienced by approximately 6% of adolescents. These adolescents had significantly poorer academic performance, poorer mental and physical health, greater substance abuse, poorer parental relationships and higher rates of consensual sexual behaviours. Gender differences in the types of abuse and the associations with abuse were found. However, there was no difference between boys and girls in the rates of experience of coercive sexual intercourse. Differences in risks were found for urban and rural school students; while rural boys were more likely to have experienced coercive sexual intercourse than urban boys (10.3% v. 2.5%), urban girls were more likely to have experienced any form of sexual abuse than rural girls (37.2% v. 25.4%). CONCLUSIONS: Abuse and violence in school-based adolescents is a common experience and is associated with poorer health and greater prevalence of risk behaviours. Interventions aimed at improving adolescent reproductive health must incorporate personal safety, prevention of abuse, communication skills and mental health issues. PMID- 11767218 TI - Sickle cell disease in Wayanad, Kerala: gene frequencies and disease characteristics. AB - BACKGROUND: A large number of patients with sickle cell anaemia are seen at the Medical College, Calicut from among the tribals and Chetti communities of the adjacent Wayanad district. We carried out a population-based study of gene frequencies and disease characteristics to plan an appropriate intervention. METHODS: Clinical examination and haemoglobin electrophoresis were done in 1016 subjects belonging to the tribal and Chetti communities in Wayanad district, by visiting hamlets and schools and evaluating everyone present at the time of the visit. RESULTS: The gene frequency of haemoglobin S ranged from 0.019 in Kattunayakan to 0.196 in Wayanadan Chettis. Wayanadan Chettis, Kurumas and Adiyas showed a high number of homozygotes with the oldest being 48 years. The survival of homozygotes is longer than what is generally recorded in other states. The disease was mild in 52.2% of cases. Painful crises were found in 43.5% and splenomegaly and leg ulcers in 4.3% each. The mean haemoglobin F rate in homozygotes was 25.9%. It was higher in clinically mild cases and in those showing an absence of irreversible sickle cells in the peripheral smear. CONCLUSIONS: The survival of patients with sickle cell anaemia seems to be higher in Kerala as compared to other states. It appears that even small improvements in primary health care available to the population (as in Kerala) are sufficient to achieve this effect. Integration of disease diagnosis and management into the already existing health care delivery system may lead to even better survival and quality of life. PMID- 11767219 TI - Management of prolonged pregnancy: a randomized trial of induction of labour and antepartum foetal monitoring. AB - BACKGROUND: The two methods of management of prolonged pregnancy, induction of labour and expectant management with foetal surveillance, have pros and cons. Therefore, we compared the induction of labour with serial antenatal foetal monitoring in the management of post-term pregnancy. METHODS: Seventy-four women with uncomplicated pregnancy at 41 weeks (287 days) of gestation were randomly assigned to undergo either induction of labour or serial antenatal foetal monitoring. Labour was induced in the latter group whenever there was evidence of foetal compromise. Antenatal monitoring consisted of the foetal kick count, non stress test and biophysical profile. RESULTS: Fifty-seven per cent of women went into spontaneous labour by 41 weeks and 4 days (291 days) of gestation and only 14% developed foetal compromise before that. However, when the gestational age was more than 41 weeks and 4 days (291 days), the incidence of meconium staining of amniotic fluid and evidence of uteroplacental insufficiency increased significantly. The rate of caesarean section, instrumental delivery, foetal distress and duration of labour did not differ significantly between the two groups. CONCLUSION: The policy of inducing labour at 41 weeks and 4 days (291 days of gestation) in uncomplicated pregnancies is justified in our population. However, foetal monitoring should begin at 41 weeks of gestation. PMID- 11767220 TI - An expert system for the diagnosis of epilepsy: results of a clinical trial. AB - BACKGROUND: Artificial intelligence is an area where computer systems are used to solve real-life problems that require expert human intelligence. Expert systems serve as an effective alternative to supplement the dearth of human experts in a narrow domain of applications. We developed an expert system named SEIZ using DIAGNOS (an expert system shell for diagnostic applications) for the diagnosis and management of epilepsy. METHODS: A clinical trial was done to test the reliability of SEIZ. The clinical and demographic data from the medical records of 50 patients with epilepsy who attended an epilepsy clinic were provided to the expert system. The system-generated diagnosis was compared with the clinical diagnosis. RESULTS: The seizure types and epileptic syndromes for the 50 patients included generalized -tonic-clonic seizure (14), absence (4), complex partial seizure (18), simple partial seizure (4), juvenile myoclonic epilepsy (5) and other epileptic syndromes (3). There were two cases of hysterical conversion reaction. There was concordance in the diagnosis between the expert system and clinician in 47 cases (94%). The overall sensitivity was 94% and the specificity was 100% for absence, generalized tonic-clonic seizures, simple partial seizures and juvenile myoclonic epilepsy; 94% for complex partial seizures and 98% for hysterical conversion reaction. CONCLUSION: This expert system could generate reliable diagnoses for patients with epilepsy. Such a system may be useful for a doctor in a remote or peripheral area where an expert on epilepsy is not available. PMID- 11767221 TI - Severe hyponatraemia: current concepts on pathogenesis and treatment. AB - Severe hyponatraemia (serum sodium <120 mEq/L) is a serious electrolyte disorder associated with life-threatening neurological complications. It develops most often when the ability of the kidney to excrete free water is impaired. The initial adaptation of the brain to hyponatraemia includes loss of water, sodium, potassium and chloride into the cerebrospinal fluid and the late adaptation consists of the loss of organic osmolytes. Adaptation of the brain to hyponatraemia causes potential problems during therapy, as re-adaptation requires a considerably longer time. Rapid correction of hyponatraemia may lead to the development of the osmotic demyelination syndrome. Though the ideal treatment for severe hyponatraemia remains controversial, a consensus regarding therapeutic guidelines has emerged. The rate of correction and the type of infusate depend on the duration and cause of the hyponatraemia, clinical presentation, volume status, renal function and the serum potassium level. The prognosis of the osmotic demyelination syndrome is rather dismal although several therapeutic modalities have been tried. PMID- 11767222 TI - Human papilloma virus and squamous cell carcinomas of the head and neck. PMID- 11767223 TI - Enteral nutrition by tube feeding in adults. AB - Patients who cannot eat enough require alternatives to oral feeding. Tube feeding is one such method for patients with a functioning gut. The techniques for the placement of feeding tubes and diets for tube feeding have improved during the past 20 years. Comfortable thin-bore polyurethane tubes are replacing the thicker vinyl tubes. Long term access routes such as gastrostomy and jejunostomy are being done by endoscopic or radiological techniques. Pre-defined formula feeds have reduced the effort and labour involved in the preparation, storage and administration of blenderized tube feeds. However, the use of soft feeding tubes and commercial formulae will increase the cost of nutrition therapy in India. The ultimate cost-effectiveness of tube feeding will depend on whether it is used appropriately during an illness with adequate delivery of feeds, and whether attention is given to small details by a dedicated nutritional support team. A strong commitment to the scientific use of nutritional support is necessary for getting the best results from tube feeding in everyday practice. PMID- 11767224 TI - Nucleic acids in therapy. AB - Human diseases have been dissected at the molecular level, and most have been found to have their bases in genetic malfunctioning. Following the age-old principle of 'set a thief to catch a thief', nucleic acids have been awarded the role of rectifying these genetic defects. Through intensive research, nucleic acids have begun to earn their rightful place as therapeutic tools, as adjuncts to traditional therapies or as definitive therapies on their own. The commercial potential of these developments in the rapidly expanding global economy is also immense. However, careful consideration of the appropriate target cells, delivery vectors, timing and dosage is essential. The ethical and social impact of the technology must also be taken into account. Besides genetic therapy (delivering 'corrective' nucleic acid sequences into the target cells), genetic medicine will have two major auxiliary impacts on human health. First, the nucleic acid sequences will increasingly provide 'tracking devices' for disease progression in response to therapy, thus serving as an adjunct to other therapeutic modalities such as radiotherapy, chemotherapy and immunotherapy. Second, the same technologies that are being developed to 'vector' the nucleic acid sequences into the target cells will become methods of delivery into these cells for novel drug molecules, which themselves will be products of genetic medicine. PMID- 11767225 TI - Recognizing emergency medicine in India. PMID- 11767226 TI - Qualitative research: a need to uncap its potential. PMID- 11767227 TI - Sub-Saharan Africa health outlook: is it totally sombre? PMID- 11767228 TI - The murky view from the single window. PMID- 11767229 TI - Pandits (priests) as links in improving the reproductive health of women: an alternative strategy. PMID- 11767230 TI - Comparison of reported drug use and urinalysis in the assessment of drug use. PMID- 11767231 TI - The soap and water treatment of burns. PMID- 11767233 TI - Selection of subjects for hospital-based epidemiologic studies based on outward manifestations of disease. AB - Selection of controls with the same outward manifestations of disease as the case group has been proposed as a means of avoiding selection bias in hospital-based case-control studies. The same strategy, however, can lead to selection bias in registry-based case-control studies that use control diseases with similar manifestations whose diagnoses might have been associated with the exposure. Matching exposed and unexposed subjects by outward manifestation of disease can be used in cohort and cross-sectional studies aiming at decreasing selection bias. This strategy in these study designs may lead to overmatching, but this will not bias the relative-risk estimates. Efficiency considerations in applying this strategy require further investigation. PMID- 11767232 TI - A comparative study of insulin lispro and human regular insulin in patients with type 2 diabetes mellitus and secondary failure of oral hypoglycemic agents. AB - OBJECTIVE: To compare the effects of insulin lispro (LP) and human regular insulin (HR) when given twice daily with NPH insulin on glycemic control (HbA1c), daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs. RESEARCH DESIGN AND METHODS: A 5.5-month randomized, open-label, parallel study of 148 patients receiving either LP (n = 70) or HR (n = 78). Eight-point blood glucose profiles and HbA1c measurements were collected at baseline, 1.5, 3.5 and 5.5 months. RESULTS: Two-hour post-breakfast and 2-hour post-supper blood glucose levels (means [and standard errors]) were significantly lower for LP than for HR at the end point (9.5 [0.4] mmol/L v. 10.9 [0.4] mmol/L and 8.4 [0.4] mmol/L v. 9.7 [0.4] mmol/L, respectively, p = 0.02 in both cases). HbA1c improved from 10.5% (0.2%) (LP) and 10.3% (0.2%) (HR) to 8.0% (0.1%). Hypoglycemia rates were similar during the day; however, there was an overnight trend to reduced rates with LP (0.08 [0.03] episodes/30 d v. 0.16 [0.04] episodes/30 d, p = 0.057). Quality-of life assessment showed significant improvement (p < 0.05) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened. CONCLUSIONS: With traditional twice-daily insulin administration algorithms, LP improves 2 hour postprandial glucose levels, quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control (HbA1c) compared with HR to insulin-naive patients with type 2 diabetes who require insulin. PMID- 11767234 TI - Adherence to antibiotic guidelines for pneumonia in chronic-care facilities in Ontario. AB - OBJECTIVES: To evaluate adherence to antibiotic recommendations for the treatment of pneumonia in patients who receive long-term care and to assess outcomes associated with these recommendations. DESIGN: A prospective cohort study. SETTING: Twenty-two facilities that provide long-term care in southern Ontario. PARTICIPANTS: Older adults treated with antibiotics for a presumptive diagnosis of pneumonia and those with radiologically confirmed pneumonia METHODS: Over a 12 month period, older patients who were treated with antibiotics for presumptive pneumonia were prospectively identified. A random sample of these antibiotic courses (646 courses in 638 patients) was reviewed using a standardized data collection form, and demographic and clinical data were collected. Antibiotic courses were classified according to Canadian and American Thoracic Society antibiotic recommendations for pneumonia. In patients with radiologically confirmed pneumonia, the effect of adherence to these recommendations on mortality and persistence of symptoms was assessed. RESULTS: Only 27.6% (178 of 646) of antibiotic prescriptions evaluated met antibiotic recommendations for nursing-home-acquired pneumonia, and the proportion meeting these varied greatly by facility, ranging from 0% to 53% (median 31%). For patients with radiologically confirmed pneumonia, age (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.4, per increase in 10 yr, p = 0.02), sex (adjusted OR 3.0, 95% CI 1.1-8.0, p = 0.03), and adherence to recommended antibiotics (OR 3.0, 95% CI 1.3-7.2, p = 0.01) were associated with death. Adherence to the recommended antibiotics was also associated with adverse reactions, which occurred in 10% of prescriptions meeting the recommendations (OR 2.4, 95% CI 1.3 4.6, p = 0.01). CONCLUSIONS: Adherence to recommended guidelines for antibiotic treatment was low and highly variable among study facilities. Use of recommended antibiotic regimens was associated with increased adverse events and worse outcomes in patients with radiologically confirmed pneumonia. PMID- 11767236 TI - A little cholesterol in time.... PMID- 11767235 TI - DHCR7 and Smith-Lemli-Opitz syndrome. PMID- 11767237 TI - Fuel spill identification using solid-phase extraction and solid-phase microextraction. 1. Aviation turbine fuels. AB - The water-soluble fraction of aviation jet fuels is examined using solid-phase extraction and solid-phase microextraction. Gas chromatographic profiles of solid phase extracts and solid-phase microextracts of the water-soluble fraction of kerosene- and nonkerosene-based jet fuels reveal that each jet fuel possesses a unique profile. Pattern recognition analysis reveals fingerprint patterns within the data characteristic of fuel type. By using a novel genetic algorithm (GA) that emulates human pattern recognition through machine learning, it is possible to identify features characteristic of the chromatographic profile of each fuel class. The pattern recognition GA identifies a set of features that optimize the separation of the fuel classes in a plot of the two largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected features is primarily about the differences between the fuel classes. PMID- 11767238 TI - A direct high-performance liquid chromatographic method for the determination of therminol 66 contamination in commercial glycerin and fatty acids. AB - A simple and sensitive high-performance liquid chromatographic method for the determination of Therminol 66 thermal heating fluid in glycerin and fatty acids is developed. Sample solutions dissolved in methanol-tetrahydrofuran (50:50, v/v) are injected directly into a reversed-phase C18 column and eluted with a methanol and water mixture (88:12, v/v). The concentration of the thermal heating fluid is monitored by fluorescence detection at 257 nm (excitation) and 320 nm (emission). The calibration graph obtained from various concentrations of the thermal heating fluid in the methanol and tetrahydrofuran mixture is linear (correlation coefficient = 0.999), and the limit of detection is 0.01 microg/mL. Spiked glycerin containing 0.1 to 1.0 microg/g of the thermal heating fluid also gives good linearity with a mean recovery of 95.3%. The mean intra- and interassay precision are 1.80-6.51% and 5.71-9.03%, respectively, at the 0.1-microg/g level. The method is simple and does not require any pretreatment step, thus it is ideal for quality assurance purposes. PMID- 11767239 TI - Chromatographic analysis of compounds of pharmaceutical interest. AB - A set of 17,600 samples belonging to our compound collection is selectively examined by liquid chromatography with UV, evaporative light scattering, and mass spectrometric detection methods. At least 70% of this set consists of pure samples with the expected structures. Subsequent studies by flow injection mass spectrometry show that this value is a conservative estimate and that the actual percentage of pure and correct compounds is close to 80%. Because this is the first time that sample quality information becomes available on such a large scale for the compound collection, it offers an opportunity to perform chemi informatic studies for which structural integrity is essential. Results of these studies can be used to improve the selection of compounds for screening and evaluate the quality of compounds from particular sources. PMID- 11767240 TI - Potential of solid-phase microextraction fibers for the analysis of volatile organic compounds in air. AB - This work presents the usefulness of five different solid-phase microextraction fibers in the screening of volatile organic compound (VOC) traces in air samples. The performances of these fibers are compared by studying the sorption kinetics in an equimolar gaseous mixture of eleven VOCs. For each fiber, static and dynamic sampling are compared. It is shown that repeatability is better for the dynamic mode (less than 6% for dynamic sampling and 10% for static sampling). The equilibrium time and the sensitivity vary considerably from one fiber type to another. As an example, the classical polydimethylsiloxane (PDMS) coating presented the shortest equilibration time (5 min) but also the poorest sensitivity, whereas the PDMS-Carboxen showed the longest extraction time but the greatest sensitivity. The estimation of the quantity of VOCs fixed on the target fiber allows for the determination of the different affinities of the compounds with the involved sorbent and relates them with physicochemical properties of the molecules. Competitive sorption is observed for the fibers involved with the adsorption process (i.e., PDMS-divinylbenzene and PDMS-Carboxen fibers). These competitions can lead to SPME calibration problems and thus bad quantitative analysis. PMID- 11767242 TI - How reversed-phase columns are made, and peak-tailing problems. PMID- 11767241 TI - Calibration of an optical condensate measurement technique using indirect static headspace gas chromatography. AB - Researchers in the Department of Mechanical Engineering seek to obtain a means to measure less than 3 mg of H2O that adheres to a metal surface as condensate. The objective is to calibrate optical reflectance measurements of an aluminum surface as a function of the condensate thickness present. Collaboration with the Hazardous Substance Research Center at Michigan State University results in the development of an indirect static headspace gas chromatographic technique capable of measuring H2O in low-milligram quantities. The technique utilizes manual headspace sampling, a megabore capillary column, and a flame ionization detector. A correlation of r2 = 0.999 is obtained for the calibration of the indirect measurement technique. The calibration of the analytical instrument demonstrates adequate precision (< +/- 50 microg at a 95% confidence interval) for such a heterogeneous sample. The calibration samples consist of a strip of aluminum metal, H2O, and pulverized calcium carbide to convert the H2O to acetylene. A scaled calibration technique is used to simplify handling trace water volumes. The surface reflectance measurements are found to correlate well (r2 = 0.935) with measurements of the condensate mass. This result facilitates the development of an optical mass-transfer measurement technique. This study focuses on the analytical method and its relationship with engineering research. PMID- 11767243 TI - Improving the signal-to-noise ratio on UV detectors. PMID- 11767244 TI - How to use evidence-based practice to distinguish between three different patients with low back pain. PMID- 11767245 TI - Systemic disease mimicking musculoskeletal dysfunction: a case report involving referred shoulder pain. PMID- 11767246 TI - Differential diagnosis of tarsal coalition versus cuboid syndrome in an adolescent athlete. PMID- 11767247 TI - Anticipatory control of vertical lifting force and momentum during the squat lift with expected and unexpected loads. AB - STUDY DESIGN: Mixed, repeated measures design. OBJECTIVES: To determine if previous experience with loads of similar weight influences the anticipatory lifting force and postural adjustments during the squat lift. To examine a multijoint, functional task for coordination between stability and movement. To determine if lifting unexpected loads results in trunk loading patterns associated with greater injury risk. BACKGROUND: Workers are increasingly exposed to variability in materials handling thereby increasing the risk of injury. Understanding the control processes underlying lifting will support clinical decision making for preparing injured workers to return to realistic working conditions. METHODS AND MEASURES: Subjects (19 men, 4 women; mean age, 25.4 +/- 3.5 y) lifted a series of boxes weighing 5%, 20%, and 35% of their maximal lifting capacity. The loads were delivered via a gravity conveyor. The identical appearing loads were ordered so that the subjects lifted several loads of similar weight, immediately followed by a lighter or heavier than expected load based on the previous lift. RESULTS: Generally, the vertical lifting force, force rate, horizontal momentum, and angular momentum increased with an increase in expected load. Higher peak lumbar extensor moments occurred with lighter than expected loads (expected 20% and lifted 5% load = 238.2 +/- 91.2 N-m; expected 35% and lifted 5% load = 278.2 +/- 101.8 N-m) compared to expected loads of similar weight (expected and lifted 5% load = 205.0 +/- 73.2 N-m). Heavier than expected loads led to eccentric trunk movements when there were large mismatches between the expected and actual loads. CONCLUSIONS: The vertical lifting forces and whole body momentum were predictively scaled according to the expected load. The loading phase relationships indicated coordination between the lifting force, force rate, horizontal momentum, and angular momentum. Trunk loading during the lifts with unexpected loads showed patterns associated with increased injury risk. PMID- 11767248 TI - Influence of joint position on electromyographic and torque generation during maximal voluntary isometric contractions of the hamstrings and gluteus maximus muscles. AB - STUDY DESIGN: Repeated measures analysis of joint angle effects on hip and knee muscle electromyographic (EMG) activity. OBJECTIVES: To simultaneously determine angle-dependent changes in maximal voluntary isometric contraction (MVIC) torque and EMG activity during hip extension and knee flexion. BACKGROUND: Procedures for normalizing EMG data and for determining torque-angle relationships for various joint motions both entail asking subjects to exert an MVIC. The implicit assumption in these paradigms is that magnitude of the EMG response is at a constant, maximum level so that observed angle-dependent variations in torque are due to mechanical factors, such as muscle length and muscle moment arm. METHODS AND MEASURES: Fifty subjects (25 men and 25 women) participated in this study (age, 23.5 +/- 4.6 y; range, 18-38 y). Subjects performed maximal isometric knee flexion at 4 knee angles and maximal isometric hip extension at 4 hip angles. The dependent variables were normalized root-mean-square EMG and torque. The process for normalizing EMG and torque data consisted of determining the largest mean value for each subject across testing positions for the muscle of interest. That value was designated as corresponding to 100% MVIC, and all other data for that muscle were expressed as a percentage of the MVIC value. Repeated measures was used to determine angle-dependent changes in normalized MVIC-torque and MVIC-EMG values for each muscle group. RESULTS: Mean torque-angle relationships were generally consistent with previous reports, though considerable intersubject variability was observed. There were significant angle-dependent differences in maximal EMG for both the hamstring and gluteus maximus muscles. Mean percentages of hamstring MVIC-EMG at knee angles of 30 degrees (81 +/- 19) and 60 degrees (82 +/- 22) were greater than at 0 degrees (68 +/- 20) or 90 degrees (74 +/- 20). The mean percentage of gluteus maximus MVIC-EMG at a hip angle of 0 degrees (94 +/- 10) was greater than at 30 degrees (84 +/- 13), 60 degrees (80 +/- 14), or 90 degrees (64 +/- 20), and gluteus maximus maximal voluntary isometric EMG at 90 degrees was less than at all other angles. These differences could not be explained solely by muscle length-dependent effects on EMG amplitude, suggesting that despite instructions for maximal effort, motor unit activation was not maintained at a constant, maximal level throughout the range of motion. The form of the EMG/angle relationships differed markedly from the torque-angle relationships. CONCLUSIONS: These findings have implications for the use of MVIC EMG for reference values in EMG normalization procedures and for the interpretation of mechanisms underlying the torque-angle relationships observed in vivo. PMID- 11767249 TI - Control of acceleration during sudden ankle supination in people with unstable ankles. AB - STUDY DESIGN: Comparative study of differences in functional control during ankle supination in the standing position in matched stable and unstable ankles (ex post facto design). OBJECTIVES: To document acceleration and deceleration during ankle supination in the standing position and to determine differences in control of supination perturbation between stable and unstable ankles. BACKGROUND: Repetitive ankle sprain can be explained by mechanical instability only in a minority of cases. Exercise therapy for ankle instability is based on clinical experience. Joint stability has not yet been measured in dynamic situations that are similar to the situations leading to a traumatic sprain. The process of motor control during accelerating ankle supination has not been adequately addressed in the literature. METHODS AND MEASURES: Patients with complaints of ankle instability (16 unstable ankles) and nonimpaired controls (18 stable ankles) were examined (N = 17 subjects, 10 women and 7 men). The average age was 23.7 +/- 5.0 years (range, 20-41 y). Control of supination speed was studied during 50 degrees of ankle supination in the standing position using accelerometry (total supination time and deceleration times) and electromyography (latency time). Timing of motor response was estimated by measuring electromechanical delay. RESULTS: The presence of an early, sudden, and presumably passive slowdown of ankle supination in the standing position was observed. Peroneal muscle motor response was detected before the end of the supination. Unstable ankles showed significantly shorter total supination time (109.3 ms versus 124.1 ms) and significantly longer latency time (58.9 ms versus 47.7 ms). CONCLUSIONS: Functional control in unstable ankles is less efficient in decelerating the ankle during the supination test procedures used in our study. Our conclusions are based on significantly faster total supination and significantly slower electromyogram response in unstable ankles. The results support the hypothesis that both decelerating the total supination movement during balance disturbance and enhancing the speed of evertor activation through exercise can be specific therapy goals. PMID- 11767250 TI - A clinician's guide to specification and sampling. AB - This article will describe and discuss the implications of various steps in the process of selecting a sample for a research study and should assist clinicians in deciding whether and how to apply specific research findings to clinical care. PMID- 11767251 TI - Tennis stroke controversy. PMID- 11767252 TI - Rethink Casey Martin: what is a right? PMID- 11767253 TI - Cellular responses and disease expression in oysters (Crassostrea virginica) exposed to suspended field contaminated sediments. AB - Exposure of oysters to water soluble fractions derived from field-contaminated sediments (FCS) containing predominantly lower molecular weight organic aromatic compounds, has been previously demonstrated to enhance pre-existing infections caused by the protozoan parasite, Perkinsus marinus (Dermo), and the prevalence of experimentally induced infections. To further explore the role of pollution on the onset and progression of disease, effects of suspended FCS from an estuarine creek in Virginia, USA, dominated by higher molecular weight polycyclic aromatic hydrocarbons (PAHs) on cellular responses and Dermo disease expression in oysters (Crassostrea virginica) were examined. Sediments were collected from a PAH polluted estuarine creek in Virginia, USA. To test effects on cellular response, oysters from Maine were exposed daily to 0, 1.0, 1.5, or 2.0 g suspended FCS (corresponding to 0, 70.2, 105, or 140 microg PAHs, respectively) for 5, 10, 20, and 40 days. Hemocyte activities and plasma lipid, protein and lactate dehydrogenase (LDH) levels were then measured. Exposure stimulated neutral red uptake, MTT reduction, and 3H-leucine incorporation in oyster hemocytes at various exposure times, but did not affect the plasma protein, lipid and LDH levels. To test effects on Dermo expression, oysters from a Dermo enzootic area, with an initial estimated infection prevalence of 39%, were exposed daily to 0, 1.0, 1.5, or 2.0 g suspended FCS (corresponding to 0, 75.0, 113, or 150 microg PAHs, respectively) for 30 days. Exposure enhanced disease expression in oysters. However, no significant change was noted in any measured cellular or humoral parameters. PMID- 11767254 TI - The marine polychaete Arenicola marina: its unusual arsenic compound pattern and its uptake of arsenate from seawater. AB - Arsenic compounds in the marine polychaete Arenicola marina collected from Odense Fjord, Denmark were determined by HPLC-ICPMS. In contrast to most other marine animals, A. marina contained most of its water soluble arsenic as inorganic forms, arsenite (58%) and arsenate (16%), and arsenobetaine was present as a minor constituent (6%) only. Other arsenic compounds detected in A. marina were dimethylarsinate (4%), two arsenosugars (1 and 3%), tetramethylarsonium ion (1.5%), and arsenocholine (<1%). A new arsenobetaine -trimethylarsoniopropionate previously only reported in fish, was also present at trace levels (<1%), and an unknown anionic arsenical (approximately 10%) remains unidentified. When A. marina was exposed in laboratory experiments to different concentrations of arsenate in seawater (10, 50. 100, 500 and 1000 microg As 1(-1)) the polychaetes accumulated arsenic in a dose dependent. non-linear manner. Most of the accumulated arsenic was biotransformed to arsenite and dimethylarsinate. with the remainder being accumulated as unchanged arsenate. None of the other arsenic compounds naturally present in A. marina increased in concentration following arsenate exposure. PMID- 11767255 TI - Coastal fish indicate human-induced changes in the Mediterranean littoral. AB - Coastal fish assemblages were studied to assess two sorts of human impacts in southwestern Apulia (SE Italy, Mediterranean Sea). Fish assemblages were evaluated by visual census along two rocky locations impacted by a sewage outfall discharging nearshore (S) and by date-mussel (Lithophaga lithophaga) fisheries (F), respectively, and at two control locations (Cs). Multivariate analyses showed that fish assemblage structures at S and F differed from those at Cs. Asymmetric ANOVAs indicated that species richness were significantly lower both at S (approximately 27%) and at F (approximately 35%) compared with Cs. Total fish abundance was 5- to 7-fold higher at S than at Cs, while the values recorded at F were comparable to those of Cs. At S, average abundances of planktivorous fish and POM feeders were higher, and those of labrids and sparids of the genus Diplodus were lower, respectively, than at Cs. Labrids of the genus Symphodus and small serranids were significantly less abundant at F than Cs. Data suggested that coastal fish respond to the impact caused by the sewage discharge and provided a framework to assess potential benefits of its future displacement to deeper waters. For the first time, moreover, this study provided suggestive evidence that the habitat destruction caused by the illegal date-mussel fisheries may affect fish assemblages. PMID- 11767256 TI - Toxicity of sediments from around a North Sea oil platform: are metals or hydrocarbons responsible for ecological impacts? AB - Discharges of contaminated drill cuttings have caused appreciable ecological change of the benthos adjacent to many oil and gas platforms in the North Sea. Many platforms have large piles of cuttings lying beneath them and these probably present the greatest potential hazard to the environment during platform decommissioning and removal. There is, however, a lack of consensus on which aspects of drill cuttings are responsible for the adverse ecological effects. This hinders risk assessment of management options. Here we report data on the toxicity of sediments from around the North West Hutton platform to the amphipod Corophium volutator, the polychaete Arenicola marina and the Microtox" acute test system. Sediment was acutely toxic to Corophium out as far as 600 m from the platform. Sediment from 100 m from the platform remained acutely toxic to Corophium when 3% contaminated sediment was mixed with clean sediment. A 10% dilution of this sediment also inhibited Arenicola feeding almost completely. Sediment elutriates did not inhibit Microtox light output, but organics extracted by dichloromethane were very toxic. Fifteen minute EC50 values were as low as 0.25 mg ml(-1) and were strongly correlated with hydrocarbon concentrations. Metal concentrations in whole sediments were correlated with their toxicity to Corophium but the relationship was much weaker when data on dilutions were included. Except at sites immediately adjacent to the platform, metal concentrations were well below ERL values from the literature, so were too low to explain sediment toxicity. Toxicity of sediments to Corophium was closely correlated with their hydrocarbon content, even when tests on dilutions were included in the analysis. We conclude that hydrocarbons are the most significant cause of toxicity in these sediments contaminated with oil based drill cuttings and that polar organics, sulphide. ammonia and other water soluble substances are of much lower significance. Applying OSPAR guidelines to our data on the toxicity of cuttings pile material to Corophium data would give a maximum allowable concentration of 0.03% in clean sediments. The Microtox data indicate that sediments from deeper in the pile would require an even greater dilution than this. PMID- 11767257 TI - Understanding binge drinking: introduction to the special issue. AB - Widespread interest in binge drinking, demonstrated by scientists, public policymakers, and educators, served as the impetus for assembling this special issue. The contents represent state-of-the-science conceptualizations and empirical work on the topic of binge drinking. This issue begins with 2 invited articles and contains a selection of empirical articles that reflect experimental and correlational designs, longitudinal studies of the course and correlates of binge drinking, and controlled-intervention trials. These articles address the construct validity of binge drinking as well as its utility as a high-risk marker in both theory-testing and intervention contexts. This introductory article discusses several advantages and disadvantages of continued use of the term binge drinking and suggests alternatives for use in research and applied contexts. PMID- 11767258 TI - Binge drinking and the American college student: what's five drinks? AB - The use of the term binge drinking and the 5/4 measure have helped to advance the understanding of college alcohol use over the past 10 years. The present article discusses the importance, relevance, and utility of this measure. PMID- 11767259 TI - Finding common ground for effective campus-based prevention. AB - This commentary reviews the controversy over use of the term binge drinking to describe college student alcohol consumption, argues for abandoning the term, and explains how doing so will help unify and reinvigorate campus-based prevention work. Binge drinking has been defined for men as 5 or more drinks in a row at least once in the previous 2 weeks and as 4 or more drinks for women. There is no scientific basis for focusing on this measure to the exclusion of other consumption measures; neither is there justification for labeling such consumption binge drinking, which reinforces an exaggerated view of student drinking. To build support for environmental management strategies to reduce alcohol-related problems, campus officials should avoid terminology that demonizes students and instead embrace the responsible majority of college students as an essential part of the solution. PMID- 11767260 TI - Binge drinking among female Veterans Affairs patients: prevalence and associated risks. AB - This study evaluated the prevalence and associated risks of binge drinking, defined as having > or = 4 drinks on an occasion in the past year, in a female patient population. Of 1,259 female Veterans Affairs patients surveyed, 780 reported drinking alcohol in the past year, and 305 (24% of respondents, 39% of drinkers) reported binge drinking in the past year; 84 (11% of drinkers) had done so monthly or more often. Age-adjusted logistic regression analyses indicated that women who reported past-year binge drinking monthly or more often reported significantly increased odds of morning drinking (odds ratio [OR] = 40.3), others worrying about their drinking (OR = 38.6), arguments after drinking (OR = 13.5), hepatitis or cirrhosis (OR = 3.1), frequent injuries (OR = 2.6), smoking (OR = 3.7), drug use (OR = 22.2), and multiple sexual partners (OR = 4.6). PMID- 11767261 TI - Binge drinking in Chinese, Korean, and White college students: genetic and ethnic group differences. AB - Studies of Asian college students have found that rates of binge drinking are associated with variation in the aldehyde dehydrogenase (ALDH2) gene. Chinese and Koreans have different prevalence rates of the ALDH2*2 allele, alcohol use, and alcoholism. The association of ALDH2 status and ethnic group with binge drinking was examined in 328 Chinese, Korean, and White college students. Ethnic group differences were found, with Whites having the highest rate of binge drinking, followed by Koreans and then Chinese. Among Asian participants, ALDH2 status and ethnicity related to binge drinking in an additive manner. Possessing an ALDH2*2 allele and being Chinese were protective factors, and being White and being Korean without an ALDH2*2 allele were risk factors for binge drinking. These results suggest that ALDH2 status, as well as other factors that differ in Koreans and Chinese, but do not interact with ALDH2, are associated with binge drinking among Asians. PMID- 11767262 TI - Defining binge drinking quantities through resulting blood alcohol concentrations. AB - Binge drinking as a researchable construct has generally been defined as 5 or more drinks on one occasion. However, no study has been conducted to determine whether the binge concept that implies excessive drunkenness is being optimally captured within that level. Random interviews of drinkers returning from visiting bars in Tijuana, with breath tests, provided both blood alcohol concentration (BAC) measurements and the self-reported number of drinks consumed. Results indicate that currently used definitions of binge drinking predict relatively low BACs and may not be capturing the excessive-drunkenness quality of the term. Consumption duration may explain the lower BACs. PMID- 11767263 TI - Estimated blood alcohol levels reached by "binge" and "nonbinge" drinkers: a survey of young adults in Montana. AB - The authors examined estimated blood alcohol concentrations (BACs) reached by so called "binge drinkers" and "nonbinge drinkers" using a survey of young adults (age 18-24 years) in Montana. One third of drinkers were classified as "binge drinkers" the last time they consumed alcohol, using a gender-specific definition commonly applied to young adults: for men, having 5 or more drinks in a row, and for women, having 4 or more drinks. BAC levels were estimated on the basis of length of drinking episode, gender, weight, and typical alcohol consumption level. Among "binge drinkers," 63% did not reach .10% BAC or higher, 48% did not reach .08% BAC or higher, and 30% did not reach .06% BAC or higher. Of the "nonbinge drinkers," 7% reached .06% BAC or higher and 4% reached .08% BAC or higher. These findings underscore the potential problem of using binge drinking as a description and shorthand measure of drinking to intoxication. PMID- 11767264 TI - Differential utility of three indexes of risky drinking for predicting alcohol problems in college students. AB - This study evaluated the relationship between alcohol-related problems and 3 indexes of risky drinking in college student drinkers: number of drinks consumed per week, frequency of binge drinking, and estimated blood alcohol levels (BALs). Use of 2 independent samples (N1 = 204, N2 = 181) allowed a cross-validation of obtained associations. Results indicated that neither binge drinking frequency nor BAL were more highly related to alcohol-related problems than was weekly drinking. Furthermore, BAL did not provide unique explanatory power in accounting for alcohol-related problems; mixed results were obtained regarding the relationship of binge drinking estimates with problems. PMID- 11767265 TI - Cognitive preoccupation with alcohol and binge drinking in college students: alcohol-induced priming of the motivation to drink. AB - This research examined alcohol-induced motivation to drink as a factor that contributes to preoccupation with drinking. Forty undergraduates rated their degree of preoccupation with drinking. The author determined the relationship between the undergraduates' preoccupation and the degree to which alcohol primed their motivation to drink by having them rate their desire for alcohol after they consumed a dose of alcohol or a placebo. Results showed that individual differences in preoccupation were predicted by the priming effects displayed after alcohol was consumed. More preoccupied individuals reported greater priming effects. Priming effects following placebo were minimal and were not related to preoccupation. The research shows that reinforcing effects of alcohol may contribute to cognitive preoccupation with drinking and promote patterns of alcohol abuse. PMID- 11767266 TI - Binge drinking among underage college students: a test of a restraint-based conceptualization of risk for alcohol abuse. AB - The authors tested a restraint-based model that binge drinking is a function of being tempted to drink alcohol while also being concerned about avoiding excessive alcohol intake. Underage (18- to 20-year-olds, 204 men and 225 women) college student drinkers completed measures that assessed the attraction to alcohol (e.g., temptation to drink, alcohol expectancies), concern about regulating alcohol intake (e.g., restriction of alcohol intake, reasons for limiting drinking), and alcohol-related outcomes (binge drinking, alcohol problems). In separate hierarchical multiple regressions, the attraction to alcohol accounted for significant amounts of additional variance in each of the alcohol outcomes. Concern about regulating alcohol intake accounted for additional variance, above that explained by attraction to alcohol. The results suggest that interventions for underage binge drinking should include training in the skills for regulating alcohol intake. PMID- 11767267 TI - Progression into and out of binge drinking among high school students. AB - The current study examined binge drinking among high school students over an academic year. Adolescent drinkers (N = 621; 58% female) were grouped into 4 trajectories: drinkers (35%), increasers (14%), decreasers (16%), and persistent binge drinkers (35%). Prospective analyses indicated several factors that predicted escalation and de-escalation of binge drinking. Increasers were more likely to regularly use alcohol and cigarettes at a younger age than drinkers. Compared with decreasers, persistent binge drinkers reported regular alcohol and marijuana use at younger ages. Lower levels of perceived student drinking appeared to be a protective factor for onset of binge drinking. The results highlight the need to study precursors to the naturally occurring fluctuations in binge drinking and suggest factors that may accentuate the risk of binge drinking. PMID- 11767268 TI - Clinical relevance of heavy drinking during the college years: cross-sectional and prospective perspectives. AB - This study investigated the clinical relevance of heavy drinking during the college years and beyond on concurrent and prospective alcohol-related problems in a high-risk sample (N = 377). Measures of heavy drinking and alcohol-related problems were significantly correlated cross-sectionally over the study frame, regardless of how these constructs were operationalized. However, the magnitude of the association between heavy drinking and alcohol-related problems declined substantially over time, with the most pronounced decrease following the college years. Despite this cross-sectional decrease in the association between heavy drinking and alcohol-related problems over time, heavy drinking during the college years significantly and substantially predicted alcohol-use disorders up to 10 years later. Implications for assessment of heavy drinking as well as prevention of problematic alcohol use in college students are discussed. PMID- 11767269 TI - Preventing binge drinking during early adolescence: one- and two-year follow-up of a school-based preventive intervention. AB - The authors examined the effectiveness of a school-based prevention program on reducing binge drinking in a sample of minority, inner-city, middle-school students. Rates of binge drinking were compared among youth who received the program beginning in the 7th grade (n = 1,713) and a control group (n = 1,328) that did not. The prevention program had protective effects in terms of binge drinking at the 1-year (8th grade) and 2-year (9th grade) follow-up assessments. The proportion of binge drinkers was over 50% lower in the intervention group relative to the control group at the follow-up assessments. There were also several significant program effects on proximal drinking variables, including drinking knowledge, pro-drinking attitudes, and peer drinking norms. These findings indicate that a school-based drug abuse prevention approach previously found to be effective among White youth significantly reduced binge drinking among urban minority youth. PMID- 11767270 TI - Examination of the short-term efficacy of a parent intervention to reduce college student drinking tendencies. AB - The research evaluated the efficacy of an intervention to reduce the onset and extent of binge drinking during the 1st year of college. The approach was on influencing the students before they start college, through their parents, during the critical time between high school graduation and the beginning of college. Specifically, parents were educated about binge drinking and how to convey information to their teens, and then encouraged to talk with their teens just before their teens embarked on their college education. Teens whose parents implemented the intervention materials were compared with a control sample during their 1st semester on drinking outcomes, perceptions about drinking activities, perceived parental and peer approval of drinking, and drinking-related consequences. As anticipated, teens in the treatment condition were significantly different (p < .05) on nearly all outcomes in the predicted directions (e.g., lower drinking tendencies, drinking consequences). The benefits of a parent-based intervention to prevent college drinking are discussed. PMID- 11767271 TI - Relative efficacy of a brief motivational intervention for college student drinkers. AB - The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students (BASICS - L. A. Dimeff, J. S. Baer, D. R. Kivlahan, & G. A. Marlatt, 1999), a single session of drinking-related feedback intended to reduce heavy drinking and related harm. College student drinkers (N = 99) were assigned to BASICS, an educational intervention, or an assessment-only control group. At 3 months postintervention. there were no overall significant group differences, but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants. At 9 months, heavier drinking BASICS participants again showed the largest effect sizes. BASICS participants evaluated the intervention more favorably than did education participants. This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students. PMID- 11767273 TI - Detection of artificially induced vertical radicular fractures using tuned aperture computed tomography. AB - This study compared the accuracy of three imaging modalities for the detection of artificially induced vertical root fractures (VRF) on teeth in cadaver mandibles. Fifty-four single-rooted, endodontically treated mandibular teeth being prepared to carry posts were evaluated using direct digital radiography (DDI) with a Schick sensor, unprocessed Tuned Aperture Computed Tomography (TACT-U) images and iteratively restored TACT (TACT-IR) images. Twenty-eight of these teeth had been subjected to fracture induction using an apically driven force. Nine basis images were used for each TACT image generation. Eight observers used a five-point confidence rating scale to record the confidence with which they considered a fracture to be present or not. Sensitivity and specificity values were computed and receiver operating characteristic (ROC) curves were generated. The areas under the curves (Az) used as an indication of the diagnostic accuracy of the imaging system were as follows: DDI: 0.37; TACT-U: 0.77 and TACT-IR: 0.81. DDI was significantly inferior to the TACT modalities. Differences in detection efficacy based on observers and observation sessions were noted on ANOVA and post hoc Tukey's tests. This study indicates that TACT is the imaging modality of choice for VRF in endodontically treated teeth. PMID- 11767272 TI - Stimulation of minor salivary glands by intraoral treatment with the cholinesterase inhibitor physostigmine in man. AB - A large number of the population, especially the elderly, suffers from dry mouth. The aim of the present investigation was to stimulate the minor salivary glands by the topical application of the cholinesterase inhibitor physostigmine. In eight healthy subjects. 100 microl of the substance, in the concentration interval 2-8 mg/ml, was applied locally to the inside of the lower lip for 1 min. In a separate study comprising 12 dry-mouth patients. 10 ml of 0.4 1.6 mg/ml physostigmine was administered as a mouth rinse solution for 2 min. Secretion from the labial glands. assessed using the Periotron method, increased in a dose dependent manner in response to physostigmine in both groups. Average peak secretion exceeded baseline by more than 50% throughout the 30- to 45-min observation period; from 1.71 to 2.62 microl cm(-2) min(-1) among the healthy subjects and from 1.17 to 1.84 microl cm 2 min among the dry mouth patients. No systemic effects were registered as reflected by ECG, heart rate or blood pressure. It is assumed that intraorally applied physostigmine diffuses through the oral mucosa and acts by preserving acetylcholine released from the cholinergic, parasympathetic nerves that innervate the minor salivary glands. The topical application of physostigmine to the oral mucosa may, therefore, be an interesting approach for the treatment of dry mouth. PMID- 11767274 TI - Burnout intervention among Dutch dentists: long-term effects. AB - The aim of the present study was to determine the long-term effects of a burnout intervention program among Dutch dentists using a longitudinal design. Using the Maslach Burnout Inventory (Dutch version: MBI-NL), at the initial measurement in 1997 a 'burnout risk group' (n = 171) was identified. This group received feedback on their scores and was invited to participate in an intervention program. Of the total group. 19 dentists participated in an intervention program. After the end of the intervention program, 92 dentists (the 19 participants and a control group) responded to a post-intervention survey in 1998. These dentists were approached once more 1 yr later, and this time 78 dentists (84.8%) returned a questionnaire. While demonstrating an improvement on all subscales of the MBI NL at the first post-test, results show that the program participants showed a relapse at the second post-test. Controls who took action on their own initiative, on the other hand, reported a beneficial effect in the long run. Finally, controls that did not take any preventive action showed little or no progress. Possible causes for these findings are discussed, including the influence of coping style. perceived control, confounding factors, demand characteristics, and the necessity of post-intervention follow-up. PMID- 11767275 TI - Effect of removable orthodontic appliances on oral colonisation by mutans streptococci in children. AB - Little is known about the effect of removable orthodontic appliances on oral colonisation by mutans streptococci (MS). In the present study, the frequency of isolation and serotype distribution of MS were evaluated in two groups of children, one undergoing therapy with removable appliances and the other not subjected to any kind of orthodontic treatment, respectively. Streptococci isolated from dental plaque samples from both groups of children were identified as mutans streptococci on the basis of their morphological and biochemical properties and were then serotyped in an enzyme immuno-assay using monoclonal antibodies. The number of subjects harbouring MS in their dental plaque was statistically higher in the group of orthodontic children without caries experience (CF) in comparison with CF children of the control group (10/12, 83.3% vs. 15/44, 34%). No clear difference was observed in the distribution of the different MS serotypes between the experimental and control group: S. mutans c,f serotype was the most frequently isolated in both groups of children followed by S. mutans serotype e and S. sobrinus serotype g. Such results suggest that the use of removable appliances may lead to the creation of new retentive areas and surfaces, which favour the local adherence and growth of MS. The data obtained stress the importance of a careful monitoring of patients treated orthodontically for risk of caries development. PMID- 11767276 TI - Actinobacillus actinomycetemcomitans-induced expression of IL-1alpha and IL-1beta in human gingival epithelial cells: role in IL-8 expression. AB - Gingival epithelial cells (GEC) are the first cells of the host that encounter the periodontal pathogens. and therefore their role in the initiation of the inflammatory response is critical. We aimed to: 1) characterize the expression of interleukin (IL)- Ialpha and IL-Ibeta in human gingiva and cultured GEC: 2) demonstrate the ability of A. actinomycetemcomitans extracts to upregulate IL 1alpha, IL-1beta and IL-8 expression in GEC in vitro: and 3) characterize the role of IL-1alpha and IL-1beta in the induction of IL-8 expression in GEC in vitro. Ten gingival biopsies (5 inflamed and 5 controls) and cultured GEC were examined for IL-1alpha and IL-Ibeta using immunohistochemical techniques. GEC were also challenged with A. actinomycetemcomitans extracts or IL-1alpha, and secretion of IL-1 and IL-8 was determined by ELISA. In vivo, IL-lalpha and IL 1beta were localized in the gingival epithelium and the infiltrating leukocytes. In vitro, A. actinomycetemcomitans extracts induced a time-dependent expression of IL-1alpha, IL-1beta and IL-8 in GEC. IL-1 inhibitors did not affect A. actinomycetemcomitans-induced IL-8. although they inhibited IL-8 induced by IL 1alpha or IL-1beta. In conclusion, GEC are a major source of IL-1alpha and IL 1beta in the periodontium, which in turn induce additional inflammatory mediators such as IL-8. Therefore GEC can be a potential target for therapeutic intervention in the future. PMID- 11767277 TI - The heat shock response of Fusobacterium nucleatum. AB - The heat-shock response of the oral Gram-negative bacterium Fusobacterium nucleatum was examined. Different strains of F. nucleatum were grown at 37 C. 42 degrees C and 48 C in the presence of [35S]methionine. Cellular proteins synthesised after shifts to higher temperatures were analysed by SDS-PAGE and autoradiography. Strains ATCC 10953, F1, F3 and Fev1 exhibited heat-shock response, and major proteins were observed at 60, 70 and 90 kDa. but increased protein synthesis was also observed for other proteins. Immunoblot analysis, using a panel of antibodies directed to epitopes on different known heat-shock proteins revealed cross-reactive proteins, indicating homology between Escherichia coli, Mycobacterium leprae and F. nucleatum heat shock proteins. PMID- 11767278 TI - Outline and arrangement of enamel rods in human deciduous and permanent enamel. 3D-reconstructions obtained from CLSM and SEM images based on serial ground sections. AB - Human enamel rods were made visible continuously from the dentino-enamel junction (DEJ) up to the enamel surface. From 12 teeth (1st and 2nd dentition) enamel blocks from the cervical third were prepared with perpendicular planes, embedded in resin, and ground down in steps of 15 microm parallel to the enamel surface. Enamel rods were made visible by acid etching (35% H3PO4, 45 s), sputtered and examined in the scanning electron microscope (SEM). Prior to this, the enamel blocks were viewed under the CLSM and optical sections at distances of 2 microm were obtained, starting in the same plane as the grinding surface. The outlines of the rods were digitized and reconstructed three dimensionally. For the first time, the path of single and grouped enamel rods on their way through the entire enamel layer was depicted. 3D images obtained from confocal laser scanning microscopy (CLSM) data were similar to those gained from SEM images. Single rods did not maintain their same outline throughout their path; arcade outlines predominated close to the DEJ, while keyhole outlines prevailed at the enamel surface. Within a group of rods, neighborhood relations changed, and neighbor rods influenced their outlines mutually, including the variable extent of the tail. The interdependence between the plasticity of the rods and the ameloblasts' forms should be topics of further research. PMID- 11767279 TI - An adenoviral system for tetracycline-regulated TGF-beta expression mediates a reversible cell cycle arrest. AB - The ability to regulate the proliferation of normal cells in a reversible manner would be a useful adjunct to some clinical therapies. including many types of cancer chemotherapy and surgery for periodontal regeneration. While the application of recombinant growth factors and cytokines to target cells is a logical approach to regulate cell proliferation, the high turnover rates of these peptide factors often make this approach impractical. Recombinant adenoviral vectors can be used to direct the expression of transgene products such as growth factors in many cell types in vitro and in vivo. We have adapted the tetracycline regulated expression system to allow regulated transforming growth factor (TGF) beta1 expression using recombinant adenovirus. We demonstrate that infection with a recombinant TGF-beta-encoding virus system in primary human oral keratinocytes and in a lung epithelial cell line is sufficient to allow a cell cycle arrest that is reversible upon tetracycline addition. This inhibition is efficient even after the infection of a minority of cells in a population. These results highlight the possibility of using low level infection with recombinant adenovirus to cause short-term blocks on cell proliferation. PMID- 11767280 TI - BMP-7 gene transfer to inflamed ferret dental pulps. AB - In vivo and ex vivo gene transfer are being developed for localized skeletal regeneration. These strategies for tissue regeneration were tested in an adult ferret model of vital pulp therapy. In this model a reversible pulpitis was induced first. Then after 3 d, the pulps were directly infected with recombinant virus or implanted with ex vivo transduced autologous dermal fibroblasts. The genome of the recombinant adenovirus contained a full-length cDNA encoding mouse bone morphogenetic protein (BMP)-7 (AdBMP7) or bacterial beta-galactosidase cDNA (AdlacZ). The BMP-7, but not lacZ, ex vivo transduced dermal fibroblasts induced reparative dentinogenesis with apparent regeneration of the dentin-pulp complex. In vivo infection with AdBMP-7 failed to produce reparative dentin in all cases. E. vivo gene transfer of BMP-7 may be an effective method for inducing dentin regeneration in teeth with reversible pulpitis. PMID- 11767281 TI - Bactericidal effect of delmopinol on attached and planktonic Streptococcus sanguinis cells. AB - The aim of this investigation was to determine the antibacterial effect of varying concentrations of delmopinol-HCl on attached as well as on planktonic Streptooccus sanguinis cells in vitro. In addition, a possible antiadhesive effect on attached micro-organisms was to be investigated. S. sanguinis cells were allowed to attach to glass surfaces. These as well as planktonic cells were exposed to delmopinol-HCI in concentrations ranging from 0.2% to 0.00005% for 2 min. The percentage of vital bacteria was calculated by means of a fluorescence staining method. Total counts of attached bacteria were performed to determine any possible detaching effect by the delmopinol-HCl. The CFU were determined for the planktonic bacteria. Attached as well as planktonic bacteria showed a marked decrease in vitality following exposure to 0.2% delmopinol-HCl. After exposure to 0.05% this was only the case with the attached microorganisms. The total number of attached bacteria was not reduced by the delmopinol treatment. During initial dental biofilm formation, delmopinol-HCl causes a bactericidal effect when applied in concentrations of 0.05% and higher. PMID- 11767282 TI - Norepinephrine transporter mRNA expression after coitus in the rabbit brainstem. AB - In the female rabbit, coitus induces a massive release of hypothalamic gonadotropin-releasing hormone (GnRH) within 20 min. The GnRH surge is preceded by an increase in hypothalamic norepinephrine (NE) release. Presumably, coitus stimulates NE, hence GnRH, release by increasing the activity of tyrosine hydroxylase (TH, the rate-limiting enzyme for NE synthesis) and/or decreasing the activity of norepinephrine transporter (NET, the key protein for NE re-uptake). Since NE cell bodies are located primarily in the brainstem, we hypothesize that coital signals are relayed to hypothalamic GnRH-secreting neurons via brainstem NE-containing perikarya. In support of this hypothesis, we found that both c-fos and TH mRNA expressions in brainstem noradrenergic areas, particularly in the A1 and A2 cell groups, increased within 30 min and returned to precoital levels within 60 min after coitus. Here we analyzed coitally induced changes in NET mRNA expression at 0, 15, 30 and 60 min postcoitus in the brainstem by in situ hybridization, using 35S-labeled rabbit NET RNA probes. In comparison with nonmated females (i.e., at 0 min), the expression of NET mRNA significantly increased (P<0.05) within 15 min postcoitus in the A1, but not the A2 area. By 30 min postcoitus, NET gene expression increased in the caudal portion of the A1 and in the caudal and central portion of the A2. By 60 min postcoitus, NET mRNA expression in the caudal and rostral portion of the A1 and the caudal and central portion of the A2 was still higher than NET mRNA expression in nonmated rabbits (P<0.05). No change in NET mRNA expression was observed in the A6. The results suggest that coitus increases NET mRNA expression in A1 and A2 noradrenergic areas within 15-30 min, and this enhanced NET mRNA expression was maintained for at least 60 min, particularly in the A2. These findings, in combination with our previous observation on increased TH gene expression within 30 min, but not 60 min, after coitus, further suggest that the coitus-induced NET transcriptional events within brainstem NE neurons may play an important role in the maintenance, and particularly in the termination, of hypothalamic NE release, hence regulating the size and duration of the coitus-induced GnRH surge. PMID- 11767283 TI - Dexamethasone enhances follicle stimulating hormone-induced P450scc mRNA expression and progesterone production in pig granulosa cells. AB - The effect of dexamethasone on follicle-stimulating hormone (FSH)-stimulated expression of cholesterol side-chain cleavage (P450scc) enzyme and production of progesterone by ovarian granulosa cells was studied in vitro. Granulosa cells from 3- to 5-mm pig antral follicles were cultured for 48 h in the presence or absence of FSH and/or dexamethasone. Treatment with FSH resulted in a dose dependent increase in the level of P450scc mRNA that reached a submaximum at 100 ng FSH/ml. This increase was associated with an increase in progesterone production. Treatment of the cells with increasing concentrations (10(-9)-10(-6) M) of dexamethasone for 48 h increased constitutive and potentiated FSH stimulated P450scc mRNA levels and progesterone production in a dose-dependent manner. Increasing duration (12-48 h) of treatment with dexamethasone (100 nM) led to a time-dependent increase in basal and FSH-stimulated progesteorne production, achieving statistical significance by 48 and 24 h, respectively. Dexamethasone also increased P450scc mRNA level and progesterone production induced by the adenylate cyclase activator forskolin (10 microM) or a cAMP analog 8-Br-cAMP (1 mM). The effects of dexamethasone on FSH-induced progesterone production were blocked by cotreatment of the cells with glucocorticoid receptor antagonist RU-486. These results demonstrate that dexamethasone potentiates FSH actions on steroidoogenesis in the pig ovary. Possible mechanisms for this potentiation include the ability of dexamethasone to stimulate P450scc gene expression. PMID- 11767284 TI - The effect of bicuculline application on auditory response properties of inferior collicular neurons of mice with or without monaural middle ear destruction in early age. AB - Previous studies have demonstrated that abnormal auditory stimulation during early postnatal development can be manifested through physiological changes that occur in the inferior colliculus (IC) of mammals. To determine the contribution of the GABAergic transmitter systems to the development of response properties of IC neurons, we examined the effect of application of bicuculline (which is an antagonist for the GABA(A) receptors) on response properties of IC neurons of the laboratory mice, Mus musculus, with or without early monaural middle ear destruction. Monaural middle ear destruction was performed at 12-14 days after birth. At adulthood, the auditory response properties of IC neurons were examined in both experimental conditions. All IC neurons determined before and during bicuculline application can be described as (1) phasic responders which discharged 1-2 impulses; (2) phasic bursters which discharged 3-7 impulse; and (3) tonic responders which discharged impulses throughout the duration of presented sound pulses. Early monaural middle ear destruction only affected the percent distribution but not the type of discharge pattern, rate-intensity function and frequency tuning curve of IC neurons in the control and experimental mice. Neurons in the contralateral IC of experimental mice typically had longer latencies, higher minimum thresholds, broader frequency tuning curves and smaller dynamic ranges than neurons in the ipsilateral IC and in control mice. Bicuculline application produced differential effects in decreasing the latencies and minimum thresholds as well as broadening frequency tuning curves and dynamic ranges of IC neurons in these two groups of mice. All these data suggest that early monaural middle ear destruction did not affect the shaping of auditory response properties of IC neurons by GABAergic transmitter system. PMID- 11767285 TI - Localization of A-type K+ channel subunit Kv4.2 in rat brain. AB - Kv4.2, a voltage-gated K+ (Kv) channel subunit, has been suggested to be the key component of the subthreshold A-type K+ currents (I(SA)s) recorded from the specific subcellular compartments of certain CNS neurons. To correlate Kv4.2 localization with the I(SA)s detected, immunohistochemistry will be useful. Although the Kv4.2 immunostaining pattern in the hippocampus and cerebellum has been reported, the Kv4.2 antibody used was not specific. Furthermore, Kv4.2 localization in other brain regions remains unclear. In this report, we first demonstrated the specificity of a new Kv4.2 antibody, and then used it to examine Kv4.2 localization throughout adult rat brain by immunohistochemistry. At the cellular level, Kv4.2 was found in neurons but not glias. At the subcellular level, Kv4.2 was localized in the somatodendritic compartment of most neurons examined. Nevertheless, our preliminary data indicated that Kv4.2 might be also present in the axon/terminal compartment. At the functional level, our data indicates that Kv4.2 localization and I(SA) correlate quite well in some CNS neurons, supporting that Kv4.2 is the key component of some I(SA)s recorded in vivo. PMID- 11767286 TI - Blockade of alpha1-adrenoceptors and cardiac depressant effect by a newly synthetic antihypertensive drug, DL-017 of quinazoline derivative. AB - The electromechanical effects of 3-[[4-(2-methoxy phenyl)piperazin-1-yl]methyl]-5 (methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a newly synthesized quinazoline-derived antihypertensive agent, on mammalian cardiac tissues were evaluated. In driven canine Purkinje fibers, DL-017 decreased twitch tension, the maximal rate of upstroke of the action potential (Vmax), and intracellular Na+ activity (a(i)Na) in a concentration-dependent manner. The action potential duration was decreased in canine Purkinje fibers but increased in guinea pig papillary muscles. In guinea pig ventricular papillary muscles, phenylephrine in the presence of 1 microM propranolol increased the twitch tension in a concentration-dependent manner. At 10 microM, phenylephrine significantly decreased a(i)Na and shortened the action potential duration. DL-017 at 0.01 microM inhibited these phenylephrine-induced effects and shifted the concentration-dependent curve to the right. In sinoatrial nodes, DL-017 inhibited pacemaker activity, involving decreases in the slope of diastolic depolarization and Vmax and an increase in a delay of repolarization. These results suggest that, in addition to blockade of alpha1-adrenoceptors and Na+ channels, DL-017 reduces cardiac excitability and contractility in association with inhibition of slow inward Ca2+ and outward K+ channels. Since two order higher concentrations are required, the contribution of DL-017 to cardiac depressant from blockade of ionic channels seems to be less important when this compound is clinically used as an antihypertensive drug. PMID- 11767287 TI - Mechanism of bifonazole-induced [Ca2+]i increases in MDCK renal tubular cells. AB - The effect of the antifungal drug bifonazole on Ca2+ homeostasis in Madin Darby canine kidney (MDCK) cells was investigated. Cell suspensions were loaded with the Ca2+-sensitive dye fura-2, and the fluorescence changes were measured with a spectrofluorophotometer. At concentrations between 10-80 microM bifonazole increased cytosolic free Ca2+ levels ([Ca2+]i) in a concentration-dependent manner. The Ca2+ signals were partly inhibited by removing extracellular Ca2+. Bifonazole (40 microM) released Ca2+ from the store sensitive to 1 microM thapsigargin, an endopolasmic reticulum Ca2+ pump inhibitor. Bifonazole (40 microM) per se induced capacitative Ca2+ entry while reduced 1 microM thapsigargin-induced capacitative Ca2+ entry. Inositol 1,4,5-trisphosphate may be involved in bifonazole-induced Ca2+ release because inhibiting phospholipase C with 2 microM U73122 partly reduced the bifonazole response. Together, bifonazole increased [Ca2+]i in renal tubular cells by inducing intracellular Ca2+ release and extracellular Ca2+ influx. PMID- 11767288 TI - Epidemiology of germ cell tumors in Asia of pineal region tumor. AB - A higher incidence of pineal region tumors in Asian countries compared to Western countries has been reported. In the Brain Tumor Registry of Japan (BTRJ), there were 38,273 primary brain tumors except those of unknown histology (1123 cases) registered in the period between 1984 and 1993, in which 807 pineal region tumors with 104 unknown histology were registered in BTRJ. Of these pineal region tumors, germ cell tumors had the highest frequency, 70.3%, followed by pineal parenchymal tumors, 12.0%; pineocytoma in 7.8% and pineoblastoma in 4.2%. Limited to germ cell tumors, germinoma was 68.0%, then teratoma including malignant teratoma, had the second high frequency, 14.7% in pineal region. While data reported by Allaire et al. and Edwards et al. revealed that the incidence of germinoma was 88.6%, 52.4% of germ cell tumors in pineal region in France and in USA, respectively. Although number of cases is very small, it is suggested that the percentage of germinoma in germ cell tumors in the pineal region might be almost the same in Western countries as in Asian countries, and the occurrence of germ cell tumors in the pineal region was much higher than those in Asia. Age and gender distribution of pineal region tumors indicated that germ cell tumors and pineocytoma showed a high incidence in males and in children. Most of malignant pineal region tumors other than germinomas showed poor prognosis, but recent progress in surgical techniques and effective chemotherapy will improve the prognosis. PMID- 11767290 TI - Pathology of pineal region tumors. AB - Various histological types of tumors arise in the pineal region. The most common tumors are pineal parenchymal tumors and germ cell tumors. Pineal parenchymal tumors are divided into pineocytoma, pineal parenchymal tumor with intermediate differentiation and pineoblastoma. Pineocytomas are well-differentiated tumors and retain the morphological and immunohistochemical features of pineal parenchymal cells. Lobular architectures and pineocytomatous rosettes are also typical features. In contrast, pineoblastomas are embryonal tumors resembling primitive neuroectodermal tumors (PNET). However, pineoblastomas are distinct from PNET in other sites due to their exhibiting photosensory differentiation including Flexner-Wintersteiner rosettes and fleurettes. Although pineal cysts are tumor-like lesions, and not true neoplasms, they are occasionally difficult to distinguish from pineocytoma and astrocytoma. From the therapeutic aspect, a precise differential diagnosis is critical. The pineal region is the most common site of the brain in which germ cell tumors occur. Germinoma, teratoma, embryonal carcinoma, yolk sac tumor and choriocarcinoma are encountered, and the latter three types of tumors usually constitute elements of mixed germ cell tumors. The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors, although there are some differences in germinoma. Pineal germinoma may exhibit carcinomatous differentiation. Other types of tumors are occasionally observed, including fibrillary and pilocytic astrocytoma, glioblastoma, ependymoma, melanoma, meningioma and so on. Metastatic pineal tumors are also rare. The most common site of origin for pineal metastasis is the lung. PMID- 11767291 TI - MRI of pineal region tumors. AB - The pineal region is a heterogeneous area that includes the pineal gland and several parapineal structures. Pineal region masses include germ cell tumors (GCTs), pineal parenchymal cell tumors, glioma, meningioma, metastases, and non neoplastic masses such as pineal cysts, lipoma, epidermoid, vascular malformations. Although MRI has allowed an improvement in distinguishing true pineal masses from parapineal masses impinging into the region of the gland, it is still difficult to differentiate the pineal GCTs from pineal parenchymal tumors with only images, and the clinical informations such as age, sex, and the tumor markers are very important. PMID- 11767292 TI - Pineal region tumor: surgical anatomy and approach. AB - The pineal region is one of the surgically inaccessible areas in the brain. Many neurovascular structures form a formidable obstacle to the operative approach to this region. The approaches suitable for reaching the pineal region are the infratentorial supracerebellar, occipital transtentorial, posterior transcallosal, posterior transcortical and posterior subtemporal routes. Considerations important in selecting one of these surgical approaches are reviewed from the anatomical viewpoint. PMID- 11767289 TI - Molecular genetics of pineal region neoplasms. AB - A large variety of mass lesions have been reported in the region of the pineal gland. Pineal parenchymal tumors and germ cell tumors (GCTs) are especially characteristic of this region. Despite their rarity, a number of excellent studies on the cytogenetics and molecular genetics of pineal parenchymal tumors and pineal region GCTs have been published. These studies draw attention to a number of distinct genomic regions recurrently involved in the various subtypes of malignancies of the pineal gland. Outcomes for tumors in this location vary widely between patients and among differing histologies. Development of novel therapies for patients with poor prognoses will depend on the acquisition of a more detailed understanding of the molecular basis associated with the etiopathogenesis of these neoplasms. We review the literature on cytogenetics, familial syndromes, animal models and molecular genetics of pineal region neoplasms. PMID- 11767293 TI - Neuroendoscopic anatomy and surgery in pineal region tumors: role of neuroendoscopic procedure in the 'minimally-invasive preferential' management. AB - The therapeutic modalities for pineal region tumors in Western countries differ from those in far-eastern countries, that is, Japan and Korea, mainly because of the different patient populations. The majority of pineal region tumors in Japan and Korea are radio sensitive and/or chemosensitive, and adjuvant therapy rather than extensive surgery plays the main part in the treatment of these tumors. The authors have applied minimally-invasive preferential management in pineal region tumors in last 8 years. For the therapeutic regimen, if the tumor markers alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG) were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third-ventriculostomy. In the results, our minimally invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure. Then avoided unnecessary craniotomy and radiotherapy and promised excellent therapeutic outcomes. Neuroendoscopic procedures have a great advantage in the management of chemo- or radiosensitive tumors, such as germinoma, pineoblastoma, or primitive neuroectodermal tumor. The neuroendoscopic anatomy including the lateral and third ventricles with a pineal region tumor with or without tumor dissemination was described in detail, together with the neuroendoscopic surgical technique. PMID- 11767294 TI - Surgical approaches to pineal region tumors. AB - Direct surgical resection of pineal region tumors has become safer, more effective, and now plays an essential role in their management. Tissue diagnosis allows for the initiation of appropriate therapies and resection can be curative or improve the efficacy of adjuvant therapies. Several approaches have been reported. Based on our operative experience with 57 patients over a 20-year period, we conclude that the Infratentorial Supracerebellar and Parieto-Occipital Paramedian Transtentorial approaches provide excellent exposure while allowing minimally invasive, relatively low risk access to the majority of pineal region tumors. Indications, positioning, techniques, advantages, and disadvantages are discussed. A review of other approaches, pertinent historical remarks, and a discussion of the role of surgery in the contemporary management of pineal region tumors are presented. PMID- 11767295 TI - Stereotactic gamma radiosurgery for pineal and related tumors. AB - The role of gamma knife radiosurgery as an additional therapy after conventional treatments for pineal and related tumors was studied in 30 of 33 tumors with a mean follow-up of 23.3 months. Overall results showed that a complete response was obtained in 8 cases (26.7%) and the response rate was 73.3%. However, tumor progression was found in 8 cases (26.7%), of whom 7 (23.3%) died as a consequence. Germinoma and pineocytoma showed higher response and control rates (100%), and neither progression nor death occurred after gamma knife treatment. Germinoma with syncytiotrophoblastic giant cells (STGC) has been thought to have an intermediate prognosis. Two of our cases showed a partial response and another progression. Malignant germ cell tumor and pineoblastoma showed unfavorable responses and prognosis, with the response and progression rates both being 50%. Gamma knife radiosurgery was the initial treatment in three pineal tumor cases without a histological diagnosis, and one complete and two partial responses were obtained. Gamma knife radiosurgery is expected to be an effective and novel approach to pineal and related tumors, not only as an adjuvant but also as an initial treatment. PMID- 11767296 TI - Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. AB - Among intracranial germ cell tumors, nongerminomatous tumors have proved refractory to conventional treatment with surgery and irradiation. The median survival is less than 2 years. Since 1983, chemotherapy has been delivered in Japan as an adjuvant therapy in patients with intracranial nongerminomatous germ cell tumors. Based on our clinical experience, we undertook a multi-institutional phase II study to establish post-surgical combined chemotherapy and radiation therapy for primary germ cell tumors in the brain. We adopted carboplatin etoposide (CARB-VP) or cisplatin-etoposide (PE) combination chemotherapy for patients with germinomas and those with tumors that placed them in the intermediate prognosis group, and ifosphamide-cisplatin-etoposide (ICE) for patients with tumors that placed them in the poor prognosis group. One hundred and twelve patients were evaluated. Among patients with germinoma (n = 75), the rate or complete remission after combination therapy was 92.0%; it was 67.8% for patients in the intermediate prognosis group (n = 28). Tumor recurrence was noted in 9 patients with germinoma and 2 patients in the intermediate prognosis group. Of 9 patients with a poor prognosis, 4 experienced disease progression during treatment and died within 10 months. There were no serious complications attributable to the combination therapy. Our treatment protocols are effective for patients with germinomas and those with an intermediate prognosis. PMID- 11767297 TI - The greater acceptance and utilization of nurse practitioners. PMID- 11767298 TI - End-of-life care: a public health crisis and an opportunity for managed care. AB - American society is failing to provide humane care for people who are dying. Unnecessary physical suffering continues even in our most prestigious institutions, and the enormous burden on family caregivers remains unrecognized. The cost of health services and burdensome regulations remain major barriers to improving the quality of care. Healthcare planners and policy makers are gradually awakening to the realities of an increasingly older population and a looming labor shortage of qualified paid caregivers. Several features of palliative care render it attractive within managed care. Evidence is emerging that palliative care, focused on meticulous prospective care planning and coordination, delivers high quality and cost-effective end-of-life care. Innovative demonstration projects around the country are exploring models for integrating palliative care within the routine operational processes and protocols of health systems and are providing examples of feasible "best practices" crucial for raising public expectations and framing possible solutions for policymakers and planners. Ultimately, it will be a marketing asset for a managed care organization to be known as a center of excellence in palliative care, and in some markets it will be a necessity. The goals of managed care and palliative care are already well aligned, joint efforts among clinicians, provider institutions, insurers, and employee health benefit managers can address the needs and preferences of dying patients and families, while increasing public trust in managed care. PMID- 11767299 TI - Fall history is an independent predictor of adverse health outcomes and utilization in the elderly. AB - OBJECTIVE: To determine whether a history of falls predicts functional decline, adverse health events, and hospitalization. STUDY DESIGN: Twelve-month prospective cohort study. PATIENTS AND METHODS: Participants were members of a Medicare managed care program. Outcomes were assessed each quarter and included functional status, healthcare utilization (hospitalization), and adverse events (hospitalizations, nursing home placement, or death). Subject healthcare utilization diaries were corroborated with health system data files. RESULTS: At baseline, 70% reported no falls (NF), 18% had 1 fall (F), and 12% reported 2 or more falls (RF). Fall status predicted functional decline; new ADL deficits were seen in 18% of NF, 28% of F, and 55% of RF (P < or = .0001). Following adjustment for baseline function, this association remained predictive (adjusted odds ratio [OR] for new ADL deficits: 3.5, P = .007; and for new ADL and IADL deficits: 12.0, P= .0001). Fall frequency was a univariate predictor of adverse events (hospitalizations, nursing home placement, or death) and of hospital utilization alone. One or more adverse event(s) occurred in 18% of NF, 22% of F, and 38% of RF (P = .049). Hospitalization occurred in 16% of NF, 22% in F, and 35% of RF (P = .03). Following adjustment for likelihood of future hospitalization (P(ra)), these associations remained predictive for RF (adjusted OR for one or more adverse event[s]: 2.4, P = .05; OR for hospitalization 2.4, P = .06). CONCLUSIONS: Fall history predicts decline in function, hospitalization, and adverse events among a Medicare managed care population and remains independently predictive of poor outcomes after controlling for baseline function and likelihood of future hospitalization. PMID- 11767300 TI - A pneumonia practice guideline and a hospitalist-based reorganization lead to equivalent efficiency gains. AB - OBJECTIVE: To compare the impact of a practice guideline for a common inpatient disorder with that of a hospitalist-based reorganization of an academic medical service. STUDY DESIGN: Retrospective cohort study. PATIENTS AND METHODS: In July 1995 we introduced a clinical practice guideline for the treatment of community acquired pneumonia at University of California San Francisco Moffitt-Long Hospital. Simultaneously, we implemented a structural change for half of the inpatient medical service, requiring earlier and more intensive faculty intervention, primarily by hospitalists. For 1 year, we studied the effect of these interventions on hospital costs, length of stay, and resource use. RESULTS: As reported previously, the hospitalist-based intervention resulted in significant decreases in average adjusted cost ($7777 vs $7007, P = .05) and length of stay (4.9 days vs 4.3 days, P = .01) compared with both concurrent and historical controls. For patients with community-acquired pneumonia, a similar savings occurred when fiscal year 1996 was compared with fiscal year 1995 ($8164 vs $6282, P= .015; 5.0 vs 4.2 days, P= .04). However, the effect was identical for the hospitalist and nonhospitalist groups. The reduced length of stay was associated with a borderline significant reduction in readmission rates (from 4.8% to 0.7%, P = .055) and no change in mortality rates. CONCLUSIONS: In this study, a hospitalist-based reorganization improved efficiency, with its greatest impact on the care of patients with disorders not covered by a practice guideline. The introduction of a guideline for a common diagnosis improved efficiency on both hospitalist- and nonhospitalist-based services. For common diagnoses amenable to practice guidelines, successful implementation of and compliance with guidelines may be an alternative to major organizational change. PMID- 11767301 TI - Financial risk, plan types, and authorizations for managed alcohol treatment services. AB - OBJECTIVE: To estimate the effects of a managed behavioral healthcare organization's (MBHO's) products/plans and financial risk on levels and amount of care authorized for patients with alcohol-related problems. STUDY DESIGN: Secondary analysis of 1995-1998 MBHO authorization files. PATIENTS: Individuals diagnosed as having an alcohol-related problem without comorbidities. METHODS: Episodes (n = 10,872) were constructed with 60-day clear zones. Multinomial regression equations were used to analyze the proportional distribution of care authorized within episodes at 5 levels: inpatient, residential, partial hospitalization, intensive outpatient, and traditional outpatient. Care equivalency hours were calculated to combine data across outpatient sessions and inpatient days. A linear regression equation analyzed quantity of care within episodes. Product/plan types, financial risk, state of residence, and participation in the MBHO's network were explanatory variables. Age, sex, diagnosis, and episode number were control variables. RESULTS: Most utilization management care hours authorized are inpatient and residential. Relative to other products/plans for managing care, utilization management leads to 50% more authorized hours. More financial risk does not predict fewer care units authorized but shifts hospitalizations toward residential treatment. Increasing age and higher-severity diagnoses predict more overnight care authorizations. Pennsylvania, which mandates minimum levels of care and follows American Society of Addiction Medicine criteria, has significantly more care authorized compared with 8 other states with data. CONCLUSIONS: Other than in utilization management, MBHO financial risk does not predict less care authorization. The MBHO authorizes higher-level care for older adults, for those with more severe diagnoses, and for those with episodes of care beyond the second. Authorization data do not necessarily reflect utilization but can provide a useful, partial view of management strategies. PMID- 11767302 TI - Leading the way: managed care for patients near the end of life. PMID- 11767303 TI - Retention of bile salts in micellar electrokinetic chromatography: relation of capacity factor to octanol-water partition coefficient and critical micellar concentration. AB - The capacity factors of 16 anionic cholates (from six bile salts, including their glyco- and tauro-conjugates) were determined in a micellar electrokinetic chromatography (MEKC) system consisting of buffer, pH 7.5 (phosphate-boric acid; 20 mmol/l) with 50 mmol/l sodium dodecyl sulfate (SDS) as micelle former and 10% acetonitrile as organic modifier. The capacity factors of the fully dissociated, negatively charged analytes (ranging between 0.2 and 60) were calculated from their mobilities, with a reference background electrolyte (BGE) without SDS representing "free" solution. For comparison, the capacity factors were derived for a second reference BGE where the SDS concentration (5 mmol/l) is close to the critical micellar concentration (CMC). The capacity factors are compared with the logarithm of the octanol-water partition coefficient, log Pow, as measure for lipophilicity. Clear disagreement between these two parameters is found especially for epimeric cholates with the hydroxy group in position 7. In contrast, fair relation between the capacity factor of the analytes and their CMC is observed both depending strongly on the orientation of the OH groups, and tauro-conjugation as well. In this respect the retention behaviour of the bile salts in MEKC seems to reflect their role as detergents in living systems, and might serve as model parameter beyond lipophilicity. PMID- 11767304 TI - Quantitative detection of bisphenol A and bisphenol A diglycidyl ether metabolites in human plasma by liquid chromatography-electrospray mass spectrometry. AB - Due to the ubiquity of epoxy resin compounds and their potential role in increasing the risk for reproductive dysfunction and cancer, the need for an assessment of human exposure is urgent. Therefore, we developed a method for measuring bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) metabolites in human blood samples using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS). Human blood samples were processed using enzymatic deconjugation of the glucuronides followed by a novel sample preparation procedure using a solid-phase-cartridge column. This selective analytical method permits rapid detection of the metabolites, free BPA and a hydrolysis product of BADGE (BADGE-40H) with detection limits in the low nanogram per milliliter range (0.1 ng ml(-1) of BPA and 0.5 ng ml(-1) of BADGE-40H). The sample extraction was achieved by Oasis HLB column on gradient elution. The recoveries of BPA and BADGE-40H added to human plasma samples were above 70.0% with a standard deviation of less than 5.0%. This selective, sensitive and accurate method will assist in elucidating potential associations between human exposure to epoxy-based compounds and adverse health effects. PMID- 11767305 TI - Gas chromatographic-mass spectrometric confirmation of atractyloside in a patient poisoned with Callilepis laureola. AB - The South African traditional remedy Impila (Callilepis laureola) contains the mitochondrial toxin atractyloside. The plant is sold widely and continues to lead to fatalities in patients. We describe, for the first time, a simple GC-MS procedure for the identification of atractyloside, which we have applied to the gastric washing from a poisoned patient and to extracts of Impila tuber. PMID- 11767307 TI - Preliminary application of liquid chromatography-electrospray-ionization mass spectrometry to the detection of 5-methyltetrahydrofolic acid monoglutamate in human plasma. AB - Liquid chromatography (LC) in direct combination with mass spectrometry (MS) has been shown to be a good analytical technique for the selective separation and detection of labile folate monoglutamates. Reversed-phase LC and electrospray ionization MS conditions were developed and optimized for the separation and detection of 5-methyltetrahydrofolic acid, 5-formyl tetrahydrofolic acid, tetrahydrofolic acid, dihydrofolic acid and folic acid in aqueous samples. Representative and reproducible positive ion mass spectra were generated for each folate under mild MS conditions. The selective MS detection and identification of endogenous 5-methyltetrahydrofolic acid in human plasma was accomplished through the development of a straightforward C18-based solid-phase extraction procedure. This procedure allows for the qualitative assessment of 5-methyltetrahydrofolic acid in plasma. Based upon an isotope-dilution internal standard calibration study with standards, the LC-MS limit of quantitation for 5M-THF was estimated to be 0.39 ng/mnl. PMID- 11767306 TI - Highly sensitive analysis of the antifolate pemetrexed sodium, a new cancer agent, in human plasma and urine by high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatography method was developed and validated for the quantitation of pemetrexed (LY231514, ALIMTA) in human urine and plasma. Plasma samples were spiked with the internal standard lometrexol and extracted using Certify II columns. Pemetrexed was assayed in diluted urine by an external calibration method. A C8 column was used for the separation of analytes with a mobile phase composed of sodium formate buffer and acetonitrile. Between- and within-day precision and accuracy were acceptable down to the limit of quantitation of 5 ng/ml in plasma. This method was used successfully for an investigation of the disposition of pemetrexed in patients receiving 500 mg/m2 as a 10-min infusion. PMID- 11767308 TI - Improved high-performance liquid chromatographic method to estimate aminosugars and its application to glycosaminoglycan determination in plasma and serum. AB - An improved isocratic high-performance liquid chromatography (HPLC) method for the analysis of L-(-)-fucose. D-(+)-galactosamine, D-(+)-glucosamine, D-(+) galactose, obtained by hydrolysis of glycosaminoglycans (GAGs) and D-(+)-glucose and D-(+)-mannose is described. The presence in circulation of GAGs, acid polysaccharide sequences of alternate monosaccharide units, aminosugar and uronic acid (galactose in keratan sulfate), has been measured in terms of their sugar components. To evaluate concentration of these circulating sugars we considered blood samples obtained from healthy humans. Plasma or serum was filtered through weak anion-exchange Ecteola-cellulose either untreated or after mild alkaline treatment. GAGs adhering to resin were recovered by salt elution, and desalted on Bio-Gel P-2 resin. GAG fractionation by charge was carried out on a strong anion exchanger. GAG composition was evaluated in terms of galactose and aminosugars, measured in HPLC by the proposed procedure using anion-exchange resin and pulsed amperometric detection. The mobile phase consisted of 0.02 M NaOH and elution was carried out at flow-rate of 1.0 ml/min. The amperometric detector was set as follows: t1 (0.5 s), E1 (+0.1 V); t2 (0.09 s), E2 (+0.6 V); t3 (0.05 s), E3 (-0.6 V). The analysis required 14 min. Calibration standard curves for the six analytes were linear from 0.25 to 40 microM. RSD values for intra- and inter-day variabilities were < or = 5.3% at concentrations between 0.25 and 40 microM. Accuracy, expressed as percentage error, ranged from - 16 to 14%. The method was specific and sensitive with quantitation limits of 1 pmol for L-(-)-fucose, D galactosamine and D-glucosamine, 3 pmol for D-(+)-galactose and D-(+)-glucose and 5 pmol for D-(+)-mannose. The results of the assay showed higher GAG concentrations in serum than in plasma. PMID- 11767310 TI - Influence of various biological matrices (plasma, blood microdialysate) on chromatographic performance in the determination of beta-blockers using an alkyl diol silica precolumn for sample clean-up. AB - A HPLC column-switching system with LiChrospher RP-8 ADS precolumn was applied for the determination of beta-blockers (atenolol, pindolol, propranolol) in human plasma. The influence of biological matrices on the changes of the chromatographic parameters such as retention time, peak symmetry, area and selectivity were investigated. After injection of 5 ml plasma a decrease of retention times of the analytes was observed of up to 25% and an increase of asymmetry factors of up to 5%. Peak areas and selectivities were not changed. The observed effect could indicate changes of chromatographic performance caused by contributions of the analytical column or the ADS precolumn. The experiments with microdialysis excluded the contribution of the analytical column. A detailed investigation of experiments have been discussed in this paper. PMID- 11767309 TI - Determination of transdermal sildenafil in nude mouse skin by reversed-phase high performance liquid chromatography. AB - A simple and sensitive high-performance liquid chromatographic method was developed for the determination of sildenafil transdermal permeation of nude mouse skin. A reversed-phase column with UV detection at 224 nm was used for chromatographic separation. The mobile phase consisted of 32% acetonitrile with 0.2% phosphoric acid in water at pH 5.3 adjusted with 10 M NaOH with the flow rate set at 1.0 ml/min. The limit of quantitation achieved was 5 ng/ml, and the calibration curve showed good linearity over the concentration range of 5-500 ng/ml. The relative standard deviations of within- and between-day analyses were all within 15%. Sildenafil was found to be stable between pH 3 and 12 during 24-h incubation with skin. After transdermal administration of 15.8 microg/ml of sildenafil to nude mouse skin, it was detected as early as 15 min. The transport amount of sildenafil could be quantitated and, at pH 8-11, had the highest permeation rate in nude mouse skin. PMID- 11767311 TI - Determination of sodium cromoglycate in human plasma by liquid chromatography mass spectrometry in the turbo ion spray mode. AB - A highly sensitivity liquid chromatography-tandem mass spectrometry method has been developed for the quantitation of sodium cromoglycate (SCG) in human plasma. The method was validated over a linear range of 0.100-50.0 ng/ml, using 13C4 sodium cromoglycate as the internal standard. Compounds were extracted from 1.0 ml of lithium heparin plasma by methanol elution of C18 solid-phase extraction cartridges. The dried residue was reconstituted with 100 microl of 0.01 N HCl. and 30 microl was injected onto the LC-MS-MS system. Chromatographic separation was achieved on a C8 (3.5 microm) column with an isocratic mobile phase of methanol-water-0.5 M ammonium acetate (35:64.8:0.2, v/v/v). The analytes were detected with a PE Sciex API 3000 mass spectrometer using turbo ion spray with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 469.2 (precursor ion) to m/z 245.1 (product ion) for SCG and m/z 473.2 (precursor ion) to m/z 247.1 (product ion) for 13C4 SCG (I.S.). The average recoveries of SCG and the I.S. from human plasma were 91 and 87%, respectively. The low limit of quantitation was 0.100 ng/ml. Results from a 4-day validation study demonstrated excellent precision (C.V.% values were between 1.9 and 6.5%) and accuracy (-5.4 to - 1.2%) across the calibration range of 0.100-50.0 ng/ml. PMID- 11767312 TI - Simultaneous determination of fifteen low-dosed benzodiazepines in human urine by solid-phase extraction and gas chromatography-mass spectrometry. AB - A gas chromatographic-mass spectrometric method was developed for the simultaneous analysis of 15 low-dosed benzodiazepines, both parent compounds and their corresponding metabolites, in human urine. The target compounds are alprazolam, alpha-hydroxyalprazolam, 4-hydroxyalprazolam, flunitrazepam, 7 aminoflunitrazepam, desmethylflunitrazepam, flurazepam, hydroxyethylflurazepam, nitrogen-desalkylflurazepam, ketazolam, oxazepam, lormetazepam, lorazepam, triazolam and alpha-hydroxytriazolam. Nitrogen-methylclonazepam is used as the internal standard. The urine sample preparation involves enzymatic hydrolysis of the conjugated metabolites with Helix pomatia beta-glucuronidase for 1 h at 56 degrees C followed by solid-phase extraction on a phenyl-type column. The extracted benzodiazepines are subsequently analyzed on a polydimethylsiloxane column using on-column injection to enhance sensitivity. The extraction efficiency exceeded 80% for all compounds except for oxazepam, lorazepam and 4 hydroxyalprazolam which had recoveries of about 60%. The LODs ranged from 13 to 30 ng/ml in the scan mode and from 1.0 to 1.7 ng/ml in the selected ion monitoring (SIM) mode. Linear calibration curves were obtained in the concentration ranges from 50 to 1000 ng/ml in the scan mode and from 5 to 100 ng/ml in the SIM mode. The within-day and day-to-day relative standard deviations at three different concentrations never exceeded 15%. PMID- 11767313 TI - Thin-layer chromatography blotting for the fluorescence detection of phospholipid hydroperoxides and cholesteryl ester hydroperoxides. AB - A blotting technique was developed to specifically detect lipid hydroperoxides in thin-layer chromatography. Phosphatidylcholine hydroperoxides and cholesteryl linoleate hydroperoxides ranging from 0.1 to 0.5 nmol, which were prepared by reaction with soybean lipoxygenase, were visualized as fluorescent spots on the blotted membrane by immersing the plate into a blotting solvent containing 0.01% (w/v) diphenyl-1-pyrenylphosphine. This technique was applied successfully to monitor lipid peroxidation in human low-density lipoprotein in vitro. PMID- 11767314 TI - Monoamine metabolite and catecholamine measurements in cerebrospinal fluid in determining the quality of the pre-operative night's sleep. AB - Temazepam 20 mg (n = 18), midazolam 15 mg (n = 14), placebo (n = 15) or no medication (n = 20) were given orally as pre-operative hypnotic in healthy patients operated on under spinal analgesia. The quality of the pre-operative night's sleep assessed subjectively was significantly better in patients receiving temazepam (P = < 0.05) and midazolam (P = < 0.05) compared with those receiving no drug. The concentrations of cortisol and monoamine neurotransmitters or their metabolites in cerebrospinal fluid were of no value in monitoring the quality of the pre-operative night's sleep. PMID- 11767315 TI - The influence of Ringer's lactate and gelatin infusion on the internal fluid balance of healthy volunteers measured by a non-invasive conductivity technique. AB - Eight healthy male volunteers received in random order at an interval of 1 week 2 litres of Ringer's lactate or 0.8 litre of gelatin (Gelofusine) over half an hour, after overnight fasting. At the end of the infusion period, blood volume and mean arterial pressure had increased significantly in both groups but the increase in blood volume was more pronounced with the colloid. Extracellular fluid volume increased significantly after Ringer's lactate, while a significant decrease was noticed after gelatin. A small decrease in intracellular fluid volume was noted after infusion of Gelofusine, whereas it did not change after infusion of Ringer's lactate. During the 30 min after infusion, blood volume decreased significantly after both treatments but after the colloid it remained higher than the initial value. During the post-infusion period, no significant changes in either intra- or extracellular volume were seen after either treatments. At the end of the study, urine production was significantly more after the Ringer's lactate. It can be concluded that infusion of 0.8 litre of gelatin results in a larger and longer lasting increase in blood volume than 2 litres of Ringer's lactate, probably due to mobilization of extracellular fluid volume. It also leads to extracellular fluid accumulation. The decrease in blood volume after infusion is caused by increased urine production, since no changes were seen in intra- and extracellular fluid volume during this period. PMID- 11767316 TI - Comparison of the cardiovascular effects of intravenous, epidural and intrathecal sufentanil analgesia as a supplement to general anaesthesia for abdominal aortic aneurysm surgery. AB - Sixty ASA Grade II-III patients, without clinical symptoms of ventricular dysfunction and scheduled for elective bifemoral grafting for abdominal aneurysms, were allocated randomly to three equal groups to receive 150 micrograms sufentanil intravenously, epidurally or intrathecally. All patients received midazolam, vecuronium and nitrous oxide. Except for right ventricular stroke work index and pulmonary vascular resistance, all haemodynamic measurements decreased after sufentanil injection, but to the greatest extent after intravenous injection. Response to abdominal incision reversed the haemodynamic changes, although this was not accompanied by an increase in heart rate and coronary perfusion pressure after intrathecal injection. Four patients given intravenous, and four patients given epidural sufentanil required additional sufentanil after abdominal incision. Despite the changes in systemic vascular resistance and the concordant alterations in cardiac index after aortic cross-clamping and revascularization, intrathecal sufentanil provided more stability in heart rate than intravenous or epidural sufentanil. In conclusion, intrathecal sufentanil produced the most stable heart rate. Two patients in the intrathecal group developed spinal headaches post-operatively. PMID- 11767318 TI - Heart rate variability and anaesthesia. PMID- 11767317 TI - Pre-oxygenation: an easy method for all elective patients. AB - The transparent plastic facemask has been investigated as a pleasant method of pre-oxygenation for elective non-high risk cases in 60 healthy ASA I or II patients randomly allocated to two groups. The patients in the pre-oxgenated group (n = 30) received 8 litre min-1 oxygen through a plastic facemask for 3 min whereas those in a control group (n = 30) were not pre-oxygenated. In all patients anaesthesia was induced with propofol 2.5 mg kg-1, fentanyl 1 ug kg-1 and atracurium 0.6 mg kg-1. Manual ventilation of the lungs using a Mapleson A breathing system was performed for 2 min with 50% oxygen in nitrous oxide prior to oral intubation. Arterial saturation in the pre-oxygenated group rose significantly from a mean baseline value of 96.4 (+/- 0.9)% to 99 (+/- 0.8)% (P < 0.01) and then remained stable both after induction and intubation: 99.1 (+/- 0.8)% and 98.9 (+/- 1.1)% respectively. In the control group arterial saturation dropped sharply within 20 s following induction to a mean of 89.8 (+/- 3.1)%, and it was 30 s before arterial saturation reached the equivalent value in the pre oxygenated group as a result of manual inflation of the lungs. An 8 litre min-1 oxygen flow via a standard transparent plastic facemask is a simple, feasible and acceptable method for routine pre-oxygenation for all elective cases. PMID- 11767319 TI - Are laser-resistant endotracheal tubes safe with the new holmium:YAG infrared laser? AB - Laser-induced ignition of the endotracheal tube is the most morbid event that may occur during laser surgery of the upper respiratory/digestive tract. The efficacy of two new laser-resistant endotracheal tubes, the Laser-Flex stainless steel tube by Mallinckrodt and the Laser-Shield II tube with teflon-aluminium-silicone coating by Xomed-Treace, was studied under exposure to a newly introduced pulsed infrared laser (holmium:YAG, lambda = 2120 nm) in an experimental setting. The time from the onset of exposure until tube perforation was recorded. Laser exposure was continued for up to 180 s unless tube ignition occurred. Temperature during the following 30 s laser application was measured close to the target zones. The irradiance level of the holmium:YAG laser was in the range required for photoablation and plasma formation and led to laser-induced tube ignition in both types of tube. The steel tube showed greater resistance to laser-induced wall damage than the teflon-aluminium silicone tube. The maximum temperature increase following laser exposure was moderate in both tubes; the mean rise of 10 degrees C for the Laser-Shield tube and 23 degrees C for the Mallinckrodt tube correlating with the physical effects of photoablation. PMID- 11767320 TI - Epidural anaesthesia for insertion of a femoral neck prosthesis in a patient with phaeochromocytoma. AB - A hemiarthroplasty for femoral neck fracture was successfully performed under combined epidural anaesthesia and light general anaesthesia before phaeochromocytoma removal. Pre-operative therapy was managed with doxazosin, enalapril and diltiazem. Peri-operative management facilitated maintenance of stable haemodynamic conditions. Post-operative pain management was provided with continuous 1% lignocaine infusion via an epidural catheter. The phaeochromocytoma was finally removed uneventfully 7 weeks after hemiarthroplasty. PMID- 11767322 TI - [Surgical treatment of subrenal aortic aneurysms. Indications at the time of endoprostheses]. PMID- 11767323 TI - [Medical chemistry in the 19th century]. PMID- 11767324 TI - [Definition and nosology of otitis]. AB - Among otitis, various classifications have been made of those that affect the middle ear during the last century. The various types of otitis media that have been described have long been considered as clearly separate entities. Only in relatively recent years has a new overall vision emerged of this disorder, which would rather be a continuum. The different types of middle ear otitis would mostly be variable expressions of a true otitis disease. PMID- 11767325 TI - [Physiopathology of inflammation of the middle ear]. AB - The middle ear plays a key role in the transmission of the sound vibrations from the tympanic drum to the inner ear. The author makes a survey of our current understanding of the maintain of air-filled cavities: muco-ciliary clearance, control of water flux across the mucosa, role of the Eustachian tube. Pathophysiology of the middle ear is primarily concerned with the major changes which occur in the middle ear in the course of secretory otitis media. These changes will allow the development of the various forms of chronic otitis media. PMID- 11767326 TI - [Epidemiology of otitis media with effusion]. AB - Acute otitis media (AOM) and otitis media with effusion (OME) are very common in the young children. The relation ship between these two pathologies has not been completely established. The AOM incidence ranges between 22 to 74%. The OME which persists after onset of AOM is more frequent (20% at 2 months) than the chronic OME which concern 4.4 to 10% of the child population before the age of five. The highest age specific incidence for all episodes of AOM is one year of age. AOM and OME are most likely to occur in the winter. The OME risk factors are: the first episode of OMA before 6 month of age, the males sex, no breastfeeding, day care centers, low socio-economic conditions and familial genetic predisposition. Passive-smoke exposure and allergy are discussed. The epidemiology assesses the actual state of these pathologies to settle, with the family, the optimum choices for the prevention. PMID- 11767327 TI - [Clinical symptomatology and diagnosis of otitis and its complications]. AB - Clinical presentation of children having an otitis media includes earache and fever. Both signs are not found in 20% of cases, while 20% of children with otitis have gastrointestinal disorders. Systematic clinical otoscopy should be performed in each child, because of the lack of value of symptoms for predicting otitis media in children. Clinical otoscopy shows first a red tympanic membrane, then a bulging eardrum, followed by an abscess of the middle ear. Otoscopy interpretation can be difficult in cases of chronic otitis media surinfection or in neonates. Otoscopy can be hard to perform: technical improvements exist, but they cannot be used in the everyday practice at home. The current complication of otitis media are facial palsy (5/1,000) and meningitis (1/1,000) leading to sequellae (deafness). PMID- 11767329 TI - [Treatment of acute otitis media in children]. AB - Acute otitis media in children have to be treated by analgesics, antipyretics and antibiotics. The choice of the antibiotic depends on the child's age, associated clinical symptoms such as conjonctivitis, and any recent history of antibiotic treatment. Children over 2 are treated by amoxicillin or CG1, children with conjunctivitis are treated by amoxicillin + clavulanate acid, infants attending day care centers and with recent history of antibiotic treatment have to be treated by cefuroxim-axetil, cefpodoximproxetil or high dosages of amoxicillin. In case of unsatisfactory course of the disease, the infecting organism has to be identified by tympanocentesis. PMID- 11767328 TI - [Microbiology in acute otitis media]. AB - Acute otitis media is the most common bacterial infection in the child under 5 years of age and the leading reason for antibiotic prescriptions in Western countries. The choice of optimal antibiotic treatment is based essentially on microbiologic epidemiologic studies. The bacteria most often responsible for otitis belong to the commensal flora of the nasopharynx. French studies using paracentesis show that the main bacteria responsible for acute otitis media are H. influenzae, S. pneumoniae and M. catarrhalis. The epidemiology of resistance to antibiotics has recently changed, with the appearance of pneumococcal strains having reduced sensitivity to penicillin, and which have played a major role in treatment failures. PMID- 11767330 TI - [Secretory otitis media]. AB - Secretory otitis media is defined as the presence of effusion behind an intact eardrum without symptoms of acute infections. It is a common problem of infants between 1 to 5 years old. Most of cases of secretory otitis media are asymptomatic and discovered during child check up. The diagnosis is otoscopic and confirmed by tympanometry. A proportion of secretory otitis media resolves spontaneously or with the treatment of upper respiratory infections. The failures require the surgical solution of ventilating tube and adenoidectomy which leads to more 90% resolution with very low side effects. PMID- 11767331 TI - [Recurrent and long-lasting otitis media in children]. AB - Recurrent otitis media is especially a social and economic problem. Treatment of risk factors generally reduces the frequency of relapses, and allows to await spontaneous improvement with age and to avoid a course toward progressive chronic otitis media. Prolonged otitis media is gradually replacing classic acute mastoiditis. Its increased incidence is correlated with the selection of increasingly resistant bacteria with the influence of antibiotic use. Treatment requires bacterial sampling and often hospitalisation for parenteral antibiotic treatment. PMID- 11767332 TI - [Medical (in)formation on Internet. On the road to knowledge or towards the Tower of Babel?]. PMID- 11767334 TI - [Red and/or painful eye diagnostic trends]. PMID- 11767333 TI - [Thyroid cancer: pathological anatomy, diagnosis]. PMID- 11767335 TI - [Acute diarrhea in adults: diagnostic trends and management in emergencies]. PMID- 11767337 TI - [Macrocytic anemia in adults: physiopathology, etiology, diagnosis and treatment]. PMID- 11767336 TI - [H2 receptor antagonists and proton pump inhibitors: principles and rules of use]. PMID- 11767338 TI - [Urogenital infections caused by gonococci and chlamydia (Nicolas Favre disease excepted): epidemiology, diagnosis, course, treatment]. PMID- 11767339 TI - [Neurotic syndrome: conversion hysteria. Diagnosis, treatment]. PMID- 11767340 TI - [Diuretics: principles and rules of use]. PMID- 11767341 TI - [Complications of venous access]. PMID- 11767342 TI - [Diffuse interstitial pneumopathy. Etiology and diagnosis]. PMID- 11767343 TI - [Non-steroidal anti-inflammatories. Principles and utilization rules]. PMID- 11767344 TI - [Bacterial endocarditis. Etiology, physiopathology, diagnosis, disease outcome, treatment]. PMID- 11767345 TI - [Iron-deficiency anemia. Etiology, physiopathology, diagnosis, treatment, with dosage for iron supplements]. PMID- 11767346 TI - [Acute anxiety attack. Diagnostic orientation and management in an emergency situation]. PMID- 11767347 TI - [Surveillance of patients immobilized in plaster]. PMID- 11767348 TI - [Extra-uterine pregnancy. Etiology, diagnosis, course of disease, treatment]. PMID- 11767350 TI - [The first artificial kidney in France]. PMID- 11767349 TI - [The Strep-test in the diagnosis of pharyngitis]. PMID- 11767351 TI - [Physiopathology of eczema]. AB - Eczema is a skin inflammatory reaction mediated by antigen-specific T cells. Two main disorders belong to this group: contact dermatitis and atopic dermatitis. The pathophysiological mecanisms involved in both disorders are similar and include, at the cellular level, three elements: the antigen (hapten or environmental antigen), antigen-presenting cells belonging to the group of dendritic cells and antigen-specific T cells. The Langerhans cell responsible for antigen handling and presentation to specific T cells appears to play a central role for the generation of the inflammatory reaction. PMID- 11767352 TI - [Atopic dermatitis]. AB - Atopic dermatitis is an extremely common condition whose prevalence is on the increasing for the past three decades particularly in North Europe, where it affects 15% of children, since birth to seventh year. A simultaneous increase of atopic respiratory disorders such as asthma and allergic rhinitis has been reported. Clinical diagnostic criteria of atopic dermatitis are well known and the recent studies concern particularly the interactions between genetic and environmental provocative factors, such as house dust mites, maternal smoking and food allergens. In susceptible families, the maternal and infants avoidance of these triggers may allow to decrease the incidence or the severity of atopic dermatitis. The conventional treatment remains symptomatic with topical steroids. However, the better understanding of pathogenesis of atopic dermatitis holds the hope of immunomodulating treatment, particularly in refractory cases. PMID- 11767353 TI - [Contact eczema]. AB - Allergic contact dermatitis is a very common condition. The causative allergens may be of environmental or occupational origin. Clinical and histological lesions are not specific. Only patch testing allow the identification of the allergen. Symptomatic treatment is the same as for any eczema. The only way to obtain a total clearance is to avoid the causative allergen. Unfortunately, some of them are quite impossible to be eliminated in daily life. For this reason, some patients tend to have chronic lesions years after onset. Recent advances in the elucidation of the skin immune system may contribute to the development of new efficacious therapeutic strategic. PMID- 11767354 TI - [Occupational eczema]. AB - Cases of occupational allergic contact dermatitis are less frequent nowadays than in the past: for instance the prevalence of allergic contact dermatitis to cement chromates is decreasing steadily among building workers. On the other hand, new haptens do occur in our environment, due to the diversification of industrial techniques; e.g. methylchloro- and methylisothiazolinone (MCI/MI) present as a preservative in paints or varnishes, acrylates and methacrylates, or, at the hospital, glutaraldehyde, propacetamol or various antibiotics. A new entity has been clinically characterized: protein contact dermatitis. The prevention of occupational allergic contact dermatitis is multidisciplinary. It includes all aspects of prevention: primary, secondary and tertiary. PMID- 11767355 TI - [Dyshidrosis]. AB - Dyshidrosis is a vesicular, non inflammatory and recurrent disease of the palms and soles related to eczema. Sometimes hyperhidrosis can induce inflammatory reactions. The diagnosis becomes obvious when a period of ferocious pruritus, vesicle develop on the sides of the fingers and the palms. These vesicles are imbedded in the epidermis below the thick stratum corneum. They are strongly distended and painful when they grow in size. They dry up and disappear within three weeks. Relapses are frequent in patients with a topy, sweat gland disorders or neurovegetative disturbances. Several clinical aspects are observed: bullous dyshidrosis, superinfection, psoriasiform keratodermia. Dyshidrosis in infectious, fungal or allergic origin can be cured by suppressing the causative agent, but complex or idiopathic lesions follow their own course and persist. PMID- 11767356 TI - [Allergy investigations in eczema]. AB - Investigation of allergy is of major importance in the diagnosis of eczema. It is mainly based on patient history: personal and familial atopic antecedents, possible contact with allergens at the work-site, in the household or during leisure activities, or in topical medications, cosmetics or clothing. Among complementary examinations, detection of eosinophilia or elevated IgE has no practical application, but sometimes the presence of specific IgE can be useful. In fact, the most important examinations are skin tests, especially patch tests, which are indispensable in contact dermatitis, and in rare cases, patch tests. PMID- 11767357 TI - [Management of atopic dermatitis]. AB - Management of atopic dermatitis should be based on cooperation among the physician, the child and the parents. There is no "radical" treatment that can eradicate the signs of this chronic affliction, which most often regresses during the first years of life. The aim of treatment is thus to combat infectious factors and to treat flares. In most cases, simple, daily and careful attention, using anti-infectious treatment, anti-inflammatory treatment by local corticosteroid application, and palliating skin dryness will assure the child of normal quality of life. PMID- 11767358 TI - [Residency in private practice (I): regulatory guidelines and patient's point of view]. PMID- 11767359 TI - [Non-traumatic meningeal hemorrhage. Etiology, diagnosis, disease outcome]. PMID- 11767360 TI - [Antibacterial antibiotics. Classification, principles and utilization rules]. PMID- 11767361 TI - [Trisomy 21. Epidemiology, diagnosis, disease outcome]. PMID- 11767362 TI - [Mycobacterium xenopi, a newcomer?]. PMID- 11767363 TI - [Medical aspects of the life of Richard Wagner]. PMID- 11767364 TI - [Physiology and functional investigation of adrenal glands]. AB - Adrenal glands are composed of a cortex producing 3 steroid hormones, namely cortisol, aldosterone and androgens, and a medulla synthesizing catecholamines. The regulation of the corticotropic axis explains the present investigation of this endocrine function including static measurements (plasmatic and urinary cortisol) and dynamic testing which are either stimulatory tests (Synacthene tests) or inhibitory tests (dexamethasone and metyrapone tests). Similarly, the physiology of the renin angiotensin system explains the exploration of the mineralo-corticoid function, which includes measurements of both qualitative and quantitative modifications of renin and aldosterone. Finally, the adrenal medulla in case of pheochromocytoma can produce an excess of catecholamines, which can be measured, themselves or their metabolites in the plasma or urines. PMID- 11767365 TI - [Imaging of adrenal glands]. AB - The technical choice in imaging the adrenal gland will depend on several factors discussed in the review. CT and MRI are achieving increasingly high accuracy in the investigation of patients suspected to present adrenal pathology. Scintigraphy evaluates functional patterns of both adrenal cortex and medulla, depending on the radiopharmaceutical that is used. Non invasive characterization of adrenal lesions is very important in cases of incidental discovery of adrenal masses. This review concentrates on new techniques for evaluating the incidentally discovered adrenal masses and differentiating between adrenal adenomas and metastases. PMID- 11767366 TI - [Adrenal insufficiency]. AB - Adrenal insufficiency can be either primitive as the result of a destruction of the glands or secondary to a corticotropic failure. Adrenal insufficiency can appear as an acute event or in contrast arise progressively. An acute adrenal insufficiency can occur any time and threatens the vital prognosis. It should be prevented by adapted treatment and education of the patient. The treatment of adrenal insufficiency includes substitutive doses of mineralo and/or glucocorticoids and, as often as possible, etiologic therapy. For this reason, as soon as the diagnosis of adrenal insufficiency has been done, a main point is to determine the cause of the endocrine failure. Indeed, some diseases responsible for adrenal deficiency, among a progressively extending list of etiologic factors, can benefit for a specific treatment. PMID- 11767367 TI - [Adrenal enzyme deficiency]. AB - The defect in 21-hydroxylase is responsible for 95% of the congenital adrenal hyperplasia. It is a recessive autosomic genetic disease with two major clinical presentation. The classical presentation is severe and frequent. It associates an adrenal deficiency with sexual ambiguity in the girl. The diagnosis is easy by measuring the plasma level of 17 OH progesterone in antenatal, perinatal samples. The non classical presentation are less severe and are clinically expressed later during the life by an hyperandrogenic syndrome. The diagnosis requires an ACTH test. In any cases, the responsible mutations on the gene CYP21 are now well known and could be identified easily by molecular biology technics. By combinating hormonal and molecular tests, it is now possible to predict the clinical form of the disease in the context of a prenatal diagnosis, which can lead to a prenatal treatment. PMID- 11767368 TI - [Cushing's syndrome]. AB - The adrenal origin of hypercorticism is established by usual hormonal and morphological investigations. Adrenal causes of Cushing syndrome are mainly due to unilateral tumours. In some cases, the remaining difficulty is evaluation of prognosis. Here, the contribution of molecular biology is likely to be major. To better understand the mechanisms of adrenal tumourigenesis, it seems essential to seek the factors modulating steroidogenesis and adrenal cells proliferation. PMID- 11767369 TI - [Pheochromocytoma]. AB - Pheochromocytoma is a tumor secreting catecholamines and is most often a sporadic and benign adrenal tumor. But in some cases the tumor is extra-adrenal (10%), malignant (10%) or familial (10%) and in this last case frequently bilateral. The clinical expression of pheochromocytoma is typically hypertension, with paroxysms including headache, excessive sweating, palpitations, but various clinical presentations can be observed. The biological diagnosis is represented by the measurement of urinary catecholamines. The most sensitive and specific test is the measurement of urinary metanephrines or of plasma methoxyamines. The tumor localization is generally easy using CT scan and (or) NMR imaging, associated with MIBG scintigraphy. The treatment is surgical after medical management. PMID- 11767370 TI - [Primary hyperaldosteronism]. AB - Any hypertension with hypokaliemia or resistant to the therapeutic requires the investigation of a primary hyperaldosteronism. The first step is to eliminate the absorption of liquorice, alkaline compounds or diuretics. The next step is to verify that the therapeutics are compatible with hormonal measurements and that urinary sodium and potassium are normal. The diagnosis is confirmed by the elevation of plasma or urinary aldosterone and a low renin concentration. Conn adenoma is present in 2/3 of the cases and is treated by surgery, whereas bilateral adrenal hyperplasies require distal diuretics. The 2 aetiological forms are distinguished by CT scan and dynamic hormonal measurements. PMID- 11767371 TI - [Adrenal incidentalomas]. AB - Since the early 1980s, incidentally discovered adrenal masses have become a common clinical problem as a result of the more widespread use of abdominal imaging procedures. Once identified, an adrenal lesion must be characterized as to its functional status and malignant potential. The evaluation of these masses include clinical, hormonal, radiological and scintigraphic data. Optimal treatment of these patients require an agreement between endocrinologist, radiologist and surgeon. The presence of an hypersecretion will prompt a surgical intervention. In the vast majority of cases, the mass will be hormonally nonhypersecretory. Than the possibility of primary or metastatic malignancy must be excluded. The arguments for benign nonhypersecretory mass are mainly a enhanced CT attenuation coefficient of 0 HU or less, a small size (< or = 3 cm of diameter), typical feature of benign mass on CT scan. In the presence of those features non further investigation are necessary, and a reevaluation will be done regularly. We recommended surgery for adrenals at high risk of malignancy: 1. CT attenuation coefficient of more than 10 HU; 2. large (> 5 cm) diameter or increase in size at any reevaluation; 3. picture of intratumoral necrosis, hemorrhage or irregular margins. PMID- 11767372 TI - [Acute intestinal invagination in infants: physiopathology, diagnosis, emergency treatment]. PMID- 11767373 TI - [Angiotensin-converting enzyme inhibitors. Principles and rules of use]. PMID- 11767374 TI - [Industrial accidents and occupational diseases. Definition]. PMID- 11767375 TI - [Acute dyspnea: diagnostic trends]. PMID- 11767376 TI - [Breast cancer: epidemiology, pathological anatomy, detection, diagnosis, course, principles of the treatment]. PMID- 11767377 TI - [Epithelial skin cancers: epidemiology, etiology, pathological anatomy, diagnosis, principles of treatment]. PMID- 11767378 TI - [Decubitus ulcers: etiology, physiopathology, prevention]. PMID- 11767379 TI - [Manic syndrome: diagnostic trends and principles of treatment]. PMID- 11767380 TI - [Recovery criteria and time in patients with pulmonary tuberculosis]. AB - A new technology of medical service of those followed up at tuberculosis control dispensaries (TCD) was developed on the basis of analysis of the data available in the literature. In doing so, the author took into account the specific features of clinical manifestations of ROT, the pattern and rates of involution of a tuberculous process with current therapeutical and diagnostic capacities borne in mind. This made it possible to define the optimum duration of a basic course of combined treatment in patients with ROT, new principles of evaluation of the outcomes of treatment, criteria for clinical recovery, as well as the procedure and duration of a follow-up. Testing this technology indicated that the latter enhanced the efficiency and profitability of TCD activities by reducing the duration of the basic course of treatment (by an average of 9-11 months), by accelerating the time of statement of ROT recovery (by 1-2 years), by decreasing follow-up periods in control TCD groups (by an average of 3 years), by drastically reducing the number of persons to receive drug therapy for preventive purposes (by 58-70%). Moreover, it may be used extensively in all regions of Russia and requires no additional logistic means and resources. PMID- 11767381 TI - [Diagnostic screening of social status in patients with pulmonary tuberculosis]. AB - In the literature there is evidence for that the mood of a patient with pulmonary tuberculosis affects the treatment and course of the disease. The necessity of special training of physicians and the duration of an examination make personality tests applied by psychologists not easily accessible to phthisiologists. The author developed methods for integral assessment of social and psychological characteristics by using questionnaire survey. He drew up a special questionnaire given in the Supplement. The questionnaire was used to study 246 middle-aged patients with pulmonary tuberculosis: 141 males aged 41.5 +/- 3.1 years and 105 females aged 42.1 +/- 2.7 years. The paper presents the data of this examination by means of this procedure. An analysis of the findings by physicians jointly with patients was a psychological correction. To provide the members of the patients' families with positive information was a form of familial counselling that is essential in assisting the patients to adapt themselves to the disease and to enhance their social activity. PMID- 11767382 TI - [Experience in using a Renex-Fluoro digital fluorograph in tuberculosis control service in Novomoskovsk]. AB - The paper outlines the design of a Russian Renex-Fluoro small-dose digital fluorograph and its operating principle. The capacities of digital fluorography in the diagnosis of different forms of pulmonary tuberculosis are considered. The data of a comparative statistical analysis of the diagnostic informative value of digital and film fluorography are given. PMID- 11767383 TI - [Diagnostic features of focal pulmonary tuberculosis in new cases]. AB - The authors examined 120 new cases of focal pulmonary tuberculosis (FPT) during the good epidemic situation years (1982-1986) and 70 patients during the poor epidemic situation years (1995-1999). The latter years were marked by a worse social composition, more frequent contacts with those isolating bacteria, a more severe course with weight loss, prolonged subfebrile temperatures, anemia, an increasing tendency for lung tissue decay and even in large foci, a more frequent bacterial isolation along with progressive immunodeficiency. New diagnostic technologies, such as computed tomography, T-lymphocytic studies at the subpopulational level by using monoclonal narrow-specific antibodies, adaptive response tests that reflect the body's responsiveness, are of value in diagnosing FPT. PMID- 11767384 TI - [Blood bacteriostatic activity in patients with respiratory tuberculosis]. AB - Vertical diffusion on the Lowenstein-Jensen medium was used to study blood bacteriostatic activity (BBA) in 174 patients with respiratory tuberculosis in relation to the drug resistance of isolated Mycobacterium tuberculosis (MT) strains and to the course of a tuberculous process. There was a clear relationship of BBA to the sensitivity of MT cultures to isoniazid: BAC was high and moderate in 90.8-98.2% of cases if strain drug sensitivity was present and low or null in 98% with drug resistance. The high and medium values of BBA correlated with the clinical indices "improvement" and "significant improvement". Patients with zero and lower values of BBA and isoniazid resistance showed a progressive specific process in 22.0% of cases. Estimation of total BBA by using liquid media is the most informative method. PMID- 11767385 TI - [Several possibilities of organizing multimodal treatment of patients with pulmonary tuberculosis]. AB - The paper analyzes the outcomes of treatment and some laboratory findings, and external respiratory function in 46 patients with destructive pulmonary tuberculosis who were treated with drugs and chest cm-range microwave radiation in an experimental group of patients receiving isoniazid lymphotropically versus a control group taking only chemotherapy. The experimental group patients showed accelerated cessation of bacterial isolation, infiltration resolution, and less residual lung changes. They also exhibited better values of external respiratory function. The serum levels of medium-weight molecules and circulating immune complexes became normal more rapidly. The immunological indices improved slowly. PMID- 11767386 TI - [Complex research studies in the testing of the effectiveness of phenaside]. PMID- 11767387 TI - [Tuberculosis situation in Russia and implementation of the Federal Tuberculosis Control Program]. PMID- 11767388 TI - [Immunopathogenetic mechanisms in the course of tuberculosis infection]. PMID- 11767389 TI - [Study of quality of life of patients with pulmonary tuberculosis]. PMID- 11767390 TI - [Effects of angiotensin-converting enzyme inhibitors and cosaar on quality of life of patients with pulmonary tuberculosis and chronic heart failure]. AB - Two and thirty four patients with pulmonary tuberculosis complicated with chronic heart failure (CHF) were examined to study life quality (LQ) and its changes due to hemodynamic correction. LQ was assessed by the Minnesota Life Heart Failure Quality questionnaire filled in by patients before and after treatment of CHF with angiotensin-converting enzyme inhibitors (captopril, ramipril, prestarium) and an angiotensin II-receptor blocker (cosaar) given for 1.5-2 months during chemotherapy for tuberculosis. In patients with pulmonary tuberculosis complicated by CHF, LQ was found to be related to the degree of hemodynamic disorders and to significantly improves with complex treatment of a tuberculous process and with correction of hemodynamic disorders. PMID- 11767391 TI - [Inhalation therapy and laser therapy in chronic bronchitis]. AB - Sixty five patients aged 24 to 68 years who had chronic bronchitis (with the rate of exacerbations of at least twice a year) in the phase of exacerbation were examined. They were 46 males and 19 females. As being examined and diagnosed, all the patients were divided into 3 groups and treated by different regimens. Sixty five took drug therapy, in 44 patients it was supplemented by endobronchial laser radiation, 22 of them also received halo therapy. Following 6-week therapy, signs of endobronchitis disappeared in a significantly larger number of patients undergone laser therapy. Moreover, there was an increase in the interval between exacerbations in patients who additionally received halo therapy. PMID- 11767392 TI - [Involvement of nitric oxide in the development of tuberculin anergy in patients with pulmonary tuberculosis]. AB - The production of nitric oxide (NO) and the magnitude of an antigen-specific proliferative response of the human lymphocytes stimulated by M. tuberculosis antigen [a purified protein derivative (PPD)] were investigated. PPD-reactive T lymphocytes were found in the peripheral blood of healthy donors. Normal values (mean values, the range of the minimum and maximum values) of PPD-induced proliferation and NO production were determined. Patients with pulmonary tuberculosis were found to have different levels of PPD-stimulated proliferation and NO production. The lymphocytes are shown to preserve their PPD reactivity in patients with normal NO production whereas the PPD-induced proliferative response was significantly decreased in those with high NO production. Patients with reduced tuberculin reactivities and high NO production were less responsive to treatment. The findings suggest that nitric oxide is involved in the development of tuberculin anergy with pulmonary tuberculosis. PMID- 11767393 TI - [Diagnostic and prognostic significance of adenosine deaminase in acutely progressive pulmonary tuberculosis]. AB - The paper provides data on the serum levels of adenosine deaminase (ADA) in patients with acutely progressive pulmonary tuberculosis (APPT). The highest levels corresponded to the severity of the disease, high bacterial isolation, the extent of destructive and infiltrative changes in lung tissue, and endotoxemia. This indicates that ADA measurement is an additional criterion for assessing the health status in APPT patients and the magnitude of destructive processes. Moreover, the measurement is of prognostic value as it provides an objective assessment of the course of an acute progressive process an the efficiency of chemotherapy used. PMID- 11767394 TI - [Comparative characterization of the antigenic composition of M. leprae and M. lufu]. AB - The antigenic structure of M. leprae and M. lufu was comparatively studied for the first time. M. lufu was found to have M. leprae-specific protein with a molecular weight of 36 kDa. M. leprae and M. lufu were similar in their fractional composition of proteins and an antibody response to determinants with equal molecular weights in patients with different forms of leprosy and its varying severity. The findings may improve a diagnostic system in leprosy by using M. lufu antigens as an alternative. PMID- 11767395 TI - [Case of secondary tuberculous glossitis]. PMID- 11767396 TI - [Case of pheochromocytoma with metastases into the lung and mediastinum]. PMID- 11767397 TI - [Tuberculous peritonitis]. PMID- 11767398 TI - [Case of abdominal tuberculosis: diagnostic problems]. PMID- 11767399 TI - [Tuberculosis in leukemia patients]. PMID- 11767400 TI - [Tuberculosis of the respiratory tract and chronic alcoholism]. AB - Tuberculosis of respiratory organs was studied in chronic alcoholics under the conditions of an industrial city the Republic of Byelarus after the Chernobyl atomic power plant accident. Respiratory tuberculosis was found to occur in chronic alcoholics more frequently than in those without chronic alcoholism, to run relatively badly, destructive form and bacterial isolation being commonly, therapeutical efficiency in them was reduced, and long-term prognosis was under question. Controlled combined anti-tuberculous and antialcoholic treatment should be performed in chronic alcoholics with tuberculosis. PMID- 11767401 TI - [Tuberculosis in A. I. Strukov's studies]. PMID- 11767402 TI - [Meeting-symposium of Chief Physicians of Tuberculosis Control Facilities of the Russian Federation on the Results of Activities in Tuberculosis Control Care of the Population in 2000]. PMID- 11767403 TI - [Prevalence of tobacco smoking among phthisio-pulmonological inpatients]. AB - A questionnaire survey of 222 phthisiopulmonological inpatients has indicated that 21.7 of the males and 4.05% of the females are smokers. Among clinical and morphological forms of tuberculosis, fibrocavernous tuberculosis is prevalent in smokers. Tuberculoma and post tuberculous fibrosis of varying severity are common in never smokers. Smokers are at high risk for lung cancer and at less risk for sarcoidosis with the equal incidence of chronic obstructive lung disease. The paper states that hospital physicians pay little attention to smoking among their patients. PMID- 11767405 TI - "Mangifera indica L. extract (QF808) reduces ischaemia-induced neuronal loss and oxidative damage in the gerbil brain". AB - The effect of oral administration of Mangifera indica L. extract (QF808) on ischemia-reperfusion-induced neuronal death in the gerbil hippocampal CA1 sector was examined. Oral administration of QF808 for 7 days dose-dependently protected against neuronal cell death following transient ischaemia and reperfusion as assessed by histopathology. In addition, locomotor activity assessment prior to ischaemia and 7 days after correlated well with the histological results. To evaluate redox alterations by reactive oxygen species, total sulfhydryl, non protein sulfhydryl groups (NPSH), malondialdehyde + 4-hydroxyalkenals and total nitrogen oxide levels were assayed in hippocampus and cortex homogenates. QF808 treatment attenuated NPSH loss, nitrogen oxide levels and lipid peroxidation in the hippocampus. These results suggest that orally administered QF808 is absorbed across the blood-brain barrier and attenuates neuronal death of the hippocampal CA1 area after ischaemia-reperfusion. These protective effects are most likely due to the antioxidant activity of QF808. PMID- 11767404 TI - Interactions of nitric oxide-derived reactive nitrogen species with peroxidases and lipoxygenases. AB - Nitric oxide (NO) is a major free radical modulator of smooth muscle tone, which under basal conditions acts to preserve vascular homeostasis through its anti inflammatory properties. The biochemistry of NO, in particular, its rapid conversion in vivo into secondary reactive nitrogen species (RNS), its chemical nature as a free radical and its high diffusibility and hydrophobicity dictate that this species will interact with numerous biomolecules and enzymes. In this review, we consider the interactions of a number of enzymes found in the vasculature with NO and NO-derived RNS. All these enzymes are either homeostatic or promote the development of atherosclerosis and hypertension. Therefore their interactions with NO and NO-derived RNS will be of central importance in the initiation and progression of vascular disease. In some examples, (e.g. lipoxygenase, LOX), such interactions provide catalytic 'sinks' for NO, but for others, in particular peroxidases and prostaglandin H synthase (PGHS), reactions with NO may be detrimental. Nitric oxide and NO-derived RNS directly modulate the activity of vascular peroxidases and LOXs through a combination of effects, including transcriptional regulation, altering substrate availability, and direct reaction with enzyme turnover intermediates. Therefore, these interactions will have two major consequences: (i) depletion of NO levels available to cause vasorelaxation and prevent leukocyte/platelet adhesion and (ii) modulation of activity of the target enzymes, thereby altering the generation of bioactive signaling molecules involved in maintenance of vascular homeostasis, including prostaglandins and leukotrienes. PMID- 11767406 TI - Isolated perfused rat hearts release secondary free radicals during ischemia reperfusion injury: cardiovascular effects of the spin trap alpha-phenyl N-tert butylnitrone. AB - Free radicals produced during myocardial post-ischemic reperfusion are aggravating factors for functional disturbances and cellular injury. The aim of our work was to investigate the significance of the secondary free radical release during non ischemic perfusion and post-ischemic reperfusion and to evaluate the cardiovascular effects of the spin trap used. For that purpose, isolated perfused rat hearts underwent 0, 20, 30 or 60 min of a total ischemia, followed by 30 min of reperfusion. The spin trap: alpha-phenyl N-tert butylnitrone (PBN) was used (3 mM). Functional parameters were recorded and samples of coronary effluents were collected and analyzed using Electron Paramagnetic Resonance (EPR) to identify and quantify the amount of spin adducts produced. During non ischemic perfusion, almost undetectable levels of free radical release were observed. Conversely, a large and long-lasting (30 min) release of spin adducts was detected from the onset of reperfusion. The free radical species were identified as alkyl and alkoxyl radicals with amounts reaching 40 times the pre-ischemic values. On the other hand, PBN showed a cardioprotective effect, allowing a significant reduction of rhythm disturbances and a better post-ischemic recovery for the hearts which were submitted to 20 min of ischemia. When the duration of ischemia increased, the protective effects of PBN disappeared and toxic effects became more important. Our results have therefore confirmed the antioxidant and protective properties of a spin trap agent such as PBN. Moreover, we demonstrated that the persistent post-ischemic dysfunction was associated with a sustained production and release of free radical species. PMID- 11767407 TI - Effect of selenolipoic acid on peroxynitrite-dependent inactivation of NADPH cytochrome P450 reductase. AB - Seleno-organic compounds are known as efficient "scavengers" of peroxynitrite (PN). Here we studied the protective effect of selenolipoic acid (SeLA), the seleno-containing analogue of lipoic acid, on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase. 3-Morpholinosydnonimine hydrochloride (SIN-1) was used as a source of peroxynitrite. The reductase was irreversibly inactivated by PN generated from SIN-1. The inactivation occurred with the rate constant of about 3 x 10(4) M-1 s-1. The presence of SeLA at low concentration (0.5 microM) led to synergistic increase of the reductase inactivation by PN. Our results suggest the formation of a reactive derivative of SeLA in the reaction of SeLA with PN, probably selenolseleninate, that mediates the aggravation of reductase inactivation. In the presence of SeLA, the inactivation was reversible under the action of thiols, allowing us to conclude that the observed action of SeLA may be considered as protective. PMID- 11767408 TI - Is homocysteine a pro-oxidant? AB - High plasma homocysteine concentrations have been found to be associated with atherosclerosis and thrombosis of arteries and deep veins. The oxidative damage mediated by hydrogen peroxide production during the metal-catalyzed oxidation of homocysteine is to date considered to be one of the major pathophysiological mechanisms for this association. In this work, a very sensitive and accurate method was employed to measure the effective production of H2O2 during homocysteine oxidation. Furthermore, the interaction of homocysteine with powerful oxidizing species (hypochlorite, peroxynitrite, ferrylmyoglobin) was evaluated in order to ascertain the putative pro-oxidant role of homocysteine. Our findings indicate that homocysteine does not produce H2O2 in a significant amount (1/4000 mole/mole ratio of H2O2 to homocysteine). Moreover, homocysteine strongly inhibits the oxidation of luminol and dihydrorhodamine by hypochlorite or peroxynitrite and rapidly reduces back ferrylmyoglobin, the oxidizing species, to metmyoglobin. All these results should, in our opinion, lead to a rethinking of the commonly held view that homocysteine oxidation is one of the main causative mechanisms of cardiovascular damage. PMID- 11767409 TI - Resistance of human cerebrospinal fluid to in vitro oxidation is directly related to its amyloid-beta content. AB - Amyloid-beta (A beta) peptide, a major constituent of senile plaques and a hallmark of Alzheimer's disease (AD), is normally secreted by neurons and can be found in low concentrations in cerebrospinal fluid (CSF) and plasma where it is associated with lipoproteins. However, the physiological role of A beta secretion remains unknown. We measured the resistance to in vitro oxidation of CSF obtained from 20 control subjects and 30 patients with AD, and correlated it with CSF levels of antioxidants, lipids and A beta. We found that the oxidative resistance, expressed as a duration of the oxidation lag-phase, was directly related to CSF levels of A beta 1-40, A beta 1-42 and ascorbate and inversely to levels of fatty acids. These data suggest that, besides ascorbate, A beta is another major physiological antioxidant for CSF lipoproteins. PMID- 11767410 TI - p38 MAPK and Ca2+ contribute to hydrogen peroxide-induced increase of permeability in vascular endothelial cells but ERK does not. AB - To examine the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) in the oxidative stress-induced increase of permeability in endothelial cells, the effects of a p38 MAPK inhibitor (SB203580) and ERK inhibitor (PD90859) on the H2O2-induced increase of permeability in bovine pulmonary artery endothelial cells (BPAEC) were investigated using a two-compartment system partitioned by a semi-permeable filter. H2O2 at 1 mM caused an increase of the permeation rate of fluorescein isothiocyanate (FITC)-labeled dextran 40 through BPAEC monolayers. SB203580 inhibited the H2O2-induced increase of permeability but PD98059 did not, though activation (phosphorylation) of both p38 MAPK and ERK was observed in H2O2 treated cells in Western blot analysis. An H2O2-induced increase of the intracellular Ca2+ concentration ([Ca2+]i) was also observed and an intracellular Ca2+ chelator (BAPTA-AM) significantly inhibited the H2O2-induced increase of permeability. However, it showed no inhibitory effects on the H2O2-induced phosphorylation of p38 MAPK and ERK. The H2O2-induced increase of [Ca2+]i was not influenced by SB203580 and PD98059. These results indicate that the activation of p38 MAPK and the increase of [Ca2+]i are essential for the H2O2-induced increase of endothelial permeability and that ERK is not. PMID- 11767411 TI - Role of membrane charge and semiquinone structure on naphthosemiquinone derivatives and 1,4-benzosemiquinone disproportionation and membrane-buffer distribution coefficients. AB - Semiquinone membrane/buffer partition coefficients have been determined for 1,2 naphthosemiquinone (ONQ.-), 1,4-naphthosemiquinone (NQ.-) and two of its hydroxylated derivatives, 5,8-dihydroxy-1,4-naphthosemiquinone (NZQ.-) and 5 hydroxy-1,4-naphthosemiquinone (JQ.-) as a function of membrane charge in multilamellar vesicles of phosphatidylcholine (PC) and equimolar mixtures of this lipid and phosphatidic acid (PC:PA) and cetyltrimethylammonium bromide (PC:CTAB) at physiological pH with the exception of values corresponding to PC:PA mixtures which were obtained at pH 9. These coefficients follow the order PC:PA < PC < PC:CTAB in agreement with the negative charge of the semiquinones. The disproportionation equilibria of the naphthosemiquinone derivatives are shifted to the semiquinone in the presence of neutral and positive membranes, being more pronounced in the latter. However, very low partition coefficients as well as small shifts in the semiquinone disproportionation equilibrium were observed for ONQ.- as compared to the other semiquinones. No partition of 1,4-benzosemiquinone (BQ.-) into the lipid phase was detected for either charged or neutral lipid membranes. The presence of lipid membranes decreases the BQ.- equilibrium concentration in the presence of all the types of membranes considered here. PMID- 11767412 TI - Chelation of hypocrellin B with zinc ions with electron paramagnetic resonance (EPR) evidence of the photodynamic activity of the resulting chelate. AB - Hypocrellin B (HB), a perylenequinone derivative, is an efficient phototherapeutic agent. The chelation of HB with Zinc ions (Zn2+) results in a metal chelate (Zn-HB) which exhibits considerable absorption (lambda max = 612 nm) in the phototherapeutic window. The structure of this chelate has been characterized by UV-Vis, IR and mass spectra. The redox potentials of the Zn-HB chelate were Eox = +1.1 V (vs. SCE) and Ere = -0.7 V (vs. SCE) as measured using the circle volt curve. The quantum yield of singlet oxygen generated by the Zn-HB chelate was 0.86, which both the electron spin trap (EPR) method and the chemical trap method show to be about 0.1 higher than that of its parent compound HB. In irradiated oxygen-saturated solutions of Zn-HB chelate, superoxide radical anions and hydroxyl radicals were detected by EPR spectroscopy using 5,5-dimethyl-1 pyrroline-N-oxide (DMPO) as the spin-trapping agent. PMID- 11767413 TI - Ferroxidases and xanthine oxidase in plasma of healthy newborn infants. AB - In the neonatal period, there is a high iron load, while both the level and molar oxidase activity of ceruloplasmin are low. On the other hand, the neonatal xanthine oxidase (XO) activity is higher than later in life and XO has a significant iron-oxidizing capacity. We therefore studied the physiological contribution of XO to the ferroxidase activity of the plasma in 20 full-term newborn infants. Ferroxidase activity was measured spectrophotometrically, with Fe++ as substrate. The uric acid formed by XO was assayed by means of HPLC, with electrochemical detection. The total ferroxidase activity in the plasma was about one-fourth of the adult level and rapidly increased doubling within 3 days after birth. About 90% of the plasma ferroxidase activity was due to ceruloplasmin, the remainder being accounted for by ferroxidase II. The XO activity underwent a 30% (statistically non-significant) elevation at 24 h, though ferroxidase activity attributable to XO was not detected at any time. Accordingly, XO does not seem to add substantially to the total iron-oxidizing capacity of the plasma in the neonatal period. The high molar ferroxidase activity is probably of importance at the endothelial cell surface. PMID- 11767414 TI - Scavenging of reactive oxygen species by chlorophyllin: an ESR study. AB - The antioxidant effects of chlorophyllin (CHL), a water-soluble analog of the green plant pigment chlorophyll, on different reactive oxygen species (ROS) were investigated by electron spin resonance (ESR) spectroscopy. As a standard, we have used the ability of CHL to scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. CHL inhibits the formation of 5,5-dimethyl-1-pyrroline-N-oxide adduct with hydroxyl radical (DMPO-.OH adduct) generated by gamma-radiation in a dose-dependent manner. At a concentration of 1 mM, CHL caused more than 90% inhibition of ESR signal intensity of this adduct. However, the results obtained with the Fenton reaction were different. We also found evidence for the inhibition of 1O2-dependent formation of the 2,2,6,6-tetramethyl-piperidine oxide (TEMPO) radical during photosensitization of methylene blue with visible light. CHL was also able to inhibit hydrogen peroxide induced oxidation of phenol red. The rate constant of the reaction of CHL with H2O2 was found to be 2.7 x 10(6) M 1 s-1. In conclusion, CHL has potent antioxidant ability involving scavenging of various physiologically important ROS. PMID- 11767415 TI - Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats. AB - The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR. PMID- 11767416 TI - Spin trapping agent, phenyl N-tert-butylnitrone, reduces nitric oxide production in the rat brain during experimental meningitis. AB - Phenyl N-tert-butylnitrone (PBN) is a spin trapping agent previously shown to exert a neuroprotective effect in infant rat brain during bacterial meningitis. In the present study, we investigated the effect of systemic PBN administration on nitric oxide (NO) production in a rat model of experimental meningitis induced by lipopolysaccharide (LPS). We assessed the NO concentration in rat brain tissues with an electron paramagnetic resonance (EPR) NO trapping technique. In this model, rats receiving intracisternal LPS administration showed symptoms of meningitis and cerebrospinal fluid (CSF) pleocytosis. The time course study indicated that the concentration of NO in the brain reached the maximum level 8.5 h after injection of LPS, and returned to the control level 24 h after the injection. When various doses of PBN (125-400 mg/kg) were injected intraperitoneally 30 min prior to LPS, NO production in the brain was reduced with increasing PBN dose (250 mg/kg suppressed 80% at 8.5 h after LPS injection), and white blood cells (WBC) in CSF were significantly decreased. We concluded that reduction of NO generation during bacterial meningitis contributes to the neuroprotective effect of PBN in addition to its possible direct scavenging of reactive oxygen intermediate (ROI). PMID- 11767418 TI - Photosensitization mechanism of active species by the complex of hypocrellin B with aluminum ion. AB - To improve the water solubility and red absorption of the parent hypocrellin B (HB), the complex of HB with aluminum ion has been first synthesized in high yield. The photodynamic action of Al(3+)-HB, especially the generation mechanism of active species, ([Al(3+)-HB].-, O2.- and 1O2) was studied using electron paramagnetic resonance (EPR) and spectrophotometric methods. In the deoxygenated DMSO solution of Al(3+)-HB, the semiquinone anion radical of Al(3+)-HB is photogenerated via the self-electron transfer between the excited and ground state species. The presence of electron donor significantly promotes the reduction of Al(3+)-HB. When oxygen is present, superoxide anion radical (O2.-) is formed via the electron transfer from [Al(3+)-HB].- to the ground state molecular oxygen. Singlet oxygen (1O2) can be produced via the energy transfer from triplet Al(3+)-HB to ground state oxygen molecules. Furthermore, it is very significant that the accumulation of [Al(3+)-HB].- would replace that of O2.- or 1O2 with the consumption of oxygen in the sealed system. PMID- 11767417 TI - Aqueous infusions of Mediterranean herbs exhibit antioxidant activity towards iron promoted oxidation of phospholipids, linoleic acid, and deoxyribose. AB - Reactive oxygen species (ROS) have been widely known to inflict biological damage upon a variety of biological sites. The ability to counteract any such activity has been the subject of this work, in an attempt to comprehend prooxidant metal ion induced oxidation and its possible physiological consequences. Five Mediterranean aqueous herb infusions have been employed in the investigation of possible pro/antioxidant activity promoted by prooxidant iron ions. In the presence of phospholipid liposomes or linoleic acid micelles or 2-deoxy-D-ribose, it was shown that all of the aqueous infusions used exhibited antioxidant activity in comparison to the iron control. The antioxidant activity, studied on 2-deoxy-D-ribose, at three concentration levels in each herb, appears to be dose dependent, albeit non-linear. The total polyphenol content of the investigated herb infusions, however, does not directly correlate with the observed antioxidant activity. The variable, yet effective, antioxidant capacity of the aqueous infusions indicates that their antioxidant components can quench ROS generating activity, brought on different substrates and likely arisen by variable mechanisms involving different ROS. PMID- 11767419 TI - Effect of consumption of phenols from olives and extra virgin olive oil on LDL oxidizability in healthy humans. AB - A high intake of olive oil has been proposed as an explanation for the low incidence of coronary heart disease in Mediterranean countries, but it is unclear whether olive oil offers specific benefits beyond a low content of saturated fat. Some types of extra virgin olive oil are rich in non-polar phenols, which might be taken up by plasma LDL particles and protect these from becoming atherogenic by oxidative modification. In a pilot study we found that consumption of 47 g fortified olive oil containing 31 mg phenols significantly increased the lag time of LDL oxidation from 112 +/- 5 min before to 130 +/- 7 min 2 h after the meal. However, this study was not controlled, and in the current study we therefore investigated whether olive oil phenols increase the lag time of LDL oxidation in postprandial samples when compared with a control group. Twelve healthy men and women consumed four different olive oil supplements with a meal on four separate occasions: one similar to the supplement in the pilot study (positive control); one containing mainly non-polar olive oil phenols; one containing mainly polar olive oil phenols; and one without phenols (placebo). Lag time significantly increased 2 h after the meals with the positive control (8 +/- 2 min), the polar phenols (8 +/- 2 min), and the placebo (8 +/- 2 min), but not after the non-polar phenols (-0.4 +/- 3 min). Increases were not statistically different between supplements. These results indicate that the lag time of LDL-oxidation is increased after consumption of a meal. This increase is probably due to non specific meal or time effects and not to phenols from olives or olive oil. Furthermore, these findings stress the need for adequate controlled studies to avoid misinterpretations of the data. PMID- 11767420 TI - Haemodynamic changes associated with thermodilution cardiac output determination during metabolic acidosis or hypoxic hypoxia in dogs. AB - Haemodynamic alterations elicited by iced injectate during thermodilution cardiac output measurements were evaluated in the presence of metabolic acidosis or hypoxic hypoxia in 14 instrumented anaesthetized dogs. The alterations in some haemodynamic variables during slowing of the heart rate following injection of 3 ml iced injectate were slightly greater in metabolic acidosis and hypoxic hypoxia as compared to animals without metabolic acidosis or hypoxic hypoxia (P < 0.05), but the changes were clinically insignificant. No serious haemodynamic changes were found during any cardiac output measurement by thermodilution in the presence of metabolic acidosis or hypoxic hypoxia. The values of cardiac output measured by thermodilution correlated closely with those of pulmonary blood flow measured by an electromagnetic flowmeter in the metabolic acidosis and hypoxic hypoxia groups (r > 0.9). It is concluded that thermodilution using iced injectate will estimate right ventricular output accurately in conditions of metabolic acidosis and hypoxic hypoxia. PMID- 11767421 TI - Clinical study of interaction between rocuronium and some commonly used antimicrobial agents. AB - The onset and duration of clinical relaxation and reversibility of rocuronium bromide (ORG 9426) 0.6 mg kg-1 were studied following administration of netilmicin 2 mg kg-1 (n = 10) or cefuroxime 20 mg kg-1 (n = 10) in patients undergoing urological surgery; and cefuroxime 20 mg kg-1 (n = 10) metronidazole 7.5 mg kg-1 (n = 10), metronidazole 7.5 mg kg-1 and cefuroxime 20 mg kg-1 (n = 10), or placebo (n = 10) in patients undergoing abdominal surgery under anaesthesia with thiopentone, nitrous oxide in oxygen, fentanyl and halothane. The antimicrobial agents were administered intravenously 5 min before rocuronium. Neuromuscular function was monitored using mechanomyography and train-of-four (TOF) mode of stimulation. Onset of neuromuscular block occurred in approximately 60 s with all patients achieving complete block. The mean clinical duration (+/- SD) was 50 +/- 10.7 and 44 +/- 6.7 min following netilmicin and cefuroxime respectively in patients undergoing urological surgery; and 49 +/- 13.7, 44 +/- 11.1, 48 +/- 11.1 and 38 +/- 7.3 min in the groups undergoing abdominal surgery receiving cefuroxime, metronidazole, cefuroxime and metronidazole combination and placebo respectively. There were no statistically significant differences between the groups in either the onset or the duration of clinical relaxation. Reversal of neuromuscular block with neostigmine carried out at spontaneous recovery of T1 (first response in the TOF) of 25% or more was easily achieved in all groups in 2 4 min. It is concluded that there is no significant interaction between rocuronium and single doses of the antimicrobial agents used in the present study. PMID- 11767422 TI - Effect of nitrous oxide on post-operative nausea and vomiting during propofol anaesthesia for short surgical operations. AB - One hundred patients of ASA status I or II, undergoing gynaecological or urological surgery were studied. Opioids were omitted from premedication and anaesthesia. Patients were allocated randomly to one of two equal groups and were anaesthetized using a computer controlled infusion system, programmed to achieve theoretically any target blood propofol concentration. One group received 60% nitrous oxide in oxygen while the other group received 100% oxygen. Six patients in the nitrous oxide group had nausea and three of these patients vomited. Two patients in the oxygen group had nausea but no patient vomited. The frequency of nausea and vomiting in the two groups was not statistically different (P > 0.05). Theoretical blood propofol concentration shown to produce surgical anaesthesia was maintained in all patients. However 12% of the patients that received nitrous oxide and 40% of the patients that did not, responded to the surgical stimulus by limb movement. Patients in the oxygen group required higher rates of propofol infusion to maintain surgical anaesthesia. PMID- 11767423 TI - Effect of different therapeutic suggestions presented during anaesthesia on post operative course. AB - A double-blind, randomized study was conducted to examine the effect of different types of therapeutic suggestions, administered during general anaesthesia, on post-operative course. Eighty-two patients undergoing cholecystectomy were intra operatively exposed to either affirmative and non-affirmative suggestions, affirmative or non-affirmative suggestions separately, or some irrelevant text. Patients who had received both affirmative and non-affirmative suggestions spent less time in hospital than patients in the other three groups. No significant differences were demonstrated for subjective well-being measured on the third and sixth days. PMID- 11767424 TI - Does epidural injection of physiological saline facilitate the advancement of catheters? AB - Seventy patients (ASA I, ASA II), scheduled for a surgical intervention under epidural or combined spinal-epidural anaesthesia, were randomly allocated to one of two groups. The epidural space was identified by loss of resistance using air, followed by injection in Group A (35 patients) of 10 ml of physiological saline directed cephallad and in Group B (35 patients) by no injection. Thereafter an anaesthetist, different to the one who placed the Tuohy in the epidural space, advanced a catheter up to 10 cm into the epidural space. At each cm of advance the resistance was judged. No significant difference in resistance was found between the groups. The authors conclude that the injection of 10 ml of physiological saline into the epidural space does not facilitate the advancement of an epidural catheter. PMID- 11767425 TI - Perineural pethidine: effects of different doses on nerve conduction. AB - Forty healthy young volunteers were divided randomly into four equal groups. 2 ml of solutions of pethidine (meperidine) in concentrations of 0.5%, 1% and 1.5% were given to three groups of 10 subjects: a fourth group received saline. Sensory evoked responses obtained via surface electrodes from both sural nerves simultaneously in the pethidine groups and unilaterally in the control group, were evaluated for latency, conduction velocity and amplitude. Sensory changes at the innervation zone were monitored by means of a pinprick. All recordings were obtained prior to injection and at 5 min intervals for 30 min. Concentrations of 1% and 1.5% pethidine were associated with significantly lower amplitudes and with hypoalgesia. Other parameters did not change. PMID- 11767426 TI - Gastric fluid pH and volume in gynaecologic out-patients. Influences of cimetidine and cimetidine-sodium citrate combination. AB - Eighty consecutive ASA physical status 1 women scheduled for day-case gynaecological laparoscopy under general anaesthesia were randomly allocated during the pre-operative visit to receive one of four premedication regimes. Patients in group 1 received hydroxyzine 100 mg; patients in group 2 received hydroxyzine 100 mg and cimetidine 400 mg; patients in group 3 received hydroxyzine 100 mg and effervescent cimetidine (cimetidine 200 mg + sodium citrate 1.8 g). All were given orally in 30 ml of water, 90 min before anaesthetic induction. Patients in group 4 received effervescent cimetidine orally in 30 ml of water 5 min before anaesthetic induction. Following induction of anaesthesia, gastric pH and residual volume (phenol red dilution technique) were measured. Gastric pH was higher (P < 0.05) in groups 2, 3 and 4 (medians: 5.71, 4.84, 6.07, respectively) than in group 1 (2.18). No patient had a gastric pH < or = 2.5 in group 4 compared with 13/14 n group 1, 1/15 in group 2 and 2/14 in group 3 (P < 0.0001). Mean gastric volumes were higher (P < 0.05) in group 4 (30.4 +/- 23.2 ml) than in groups 1, 2 and 3 (11.8 +/- 6.4, 15.8 +/- 11.2, 17.2. +/- 24.4 ml, respectively). Nine of the 19 patients in group 4 had a volume higher than 25 ml. Only one patient in group 1 had both gastric pH < or = 2.5 and volume > or = 25 ml. The administration of effervescent cimetidine 5 min prior to anaesthetic induction seems to be an easy and effective method of decreasing the acidity of gastric contents in day surgery. PMID- 11767427 TI - Fibreoptic bronchoscopy under general anaesthesia using the laryngeal mask airway. AB - The laryngeal mask airway was used to facilitate fibreoptic bronchoscopy under general anaesthesia in 140 adult patients. Following placement, the position of the mask was observed through the fibreoptic bronchoscope. Three different positions were identified. In 120 patients (86%) the concave surface of the mask faced the larynx directly with or without some unfolding of the epiglottis. In 17 patients (12%) the laryngeal mask appeared to be at an angle facing one pyriform fossa and in two patients the tip of the mask lay anterior to the arytenoids. No problems with ventilation or maintenance of an acceptable airway were encountered. In one patient repositioning of the laryngeal mask was necessary to allow the passage of the bronchoscope. One patient developed laryngospasm and required tracheal intubation. PMID- 11767428 TI - Spirometry, blood gas analysis and ultrasonography of the diaphragm after Winnie's interscalene brachial plexus block. AB - Ten patients with healthy lungs were subjected to radiology, sonography, spirometry and blood gas analysis before and after an interscalene brachial plexus block prior to shoulder surgery. Winnie's interscalene block induced ipsilateral hemidiaphragmatic paresis that was confirmed by radiology and sonography. Changes in forced expiratory vital capacity (FVC), forced expiratory volume (FEV1) and peak expiratory flow rate (PEFR) were significant and PaO2 declined by an average of 1.3 kPa. These changes should not cause further clinical symptoms in sitting patients with unaffected lungs. In patients with pulmonary disease, this method of nerve block should be limited to cases for which there is a clear indication. PMID- 11767429 TI - Changes in recording electrode impedance during anaesthesia have no effect on evoked electromyographic responses. AB - Changes in electrical impedance at the recording electrodes have been blamed for the failure of evoked electromyographic responses to return to baseline during the offset of neuromuscular block, but a relationship between electrode impedance and electromyographic responses has never been shown. In 50 fit adults, the resistive and capacitive (reactive) components of the impedance of the recording electrodes were measured during electromyographic monitoring of neuromuscular transmission under enflurane anaesthesia. In 25 patients six 1 mm-deep punctures were made in the skin under both active recording electrodes, and in the other 25 no puncture was made. Electrode impedance was measured using an impedance bridge at a current density less than 60 microA cm-2. Skin puncture made no difference either to the electrode impedance, or to the decrement from the baseline of the first electromyographic response to the train-of-four stimuli after offset of neuromuscular blockade. The electrode impedance decreased in 48 of the patients, and increased slightly in the other two patients. There was no relationship between the decrease in the T1 response from baseline and the change in electrode impedance during electromyographic monitoring. PMID- 11767430 TI - Spinal anaesthesia for familial hypokalaemic periodic paralysis. PMID- 11767431 TI - Core and mean body temperature (MBT) changes that occur during prolonged faciomaxillary surgery with two differing anaesthetic techniques. PMID- 11767432 TI - Recurring hepatic hydrothorax: a difficult therapeutic challenge. PMID- 11767433 TI - Complications of thoracentesis in cirrhotic patients with pleural effusion. AB - OBJECTIVE: To study the complications of thoracentesis, either diagnostic or therapeutic, in cirrhotic patients with pleural effusion. EXPERIMENTAL DESIGN: A cohort prospective study. A diagnostic thoracentesis was performed at admission or when spontaneous bacterial empyema was suspected; a therapeutic thoracentesis was conducted in patients with dyspnea that did not improve with medical treatment. A chest radiography and a careful clinical follow up were performed in all patients within 24 hours after the procedure. We studied the risk factors for developing pneumothorax and the actuarial probability of pneumothorax after consecutive therapeutic thoracentesis. PATIENTS: All cirrhotic patients admitted with pleural effusion over a 4-year period. The study included 69 patients. RESULTS: During the study period, we performed 245 thoracentesis, 150 diagnostic and 95 therapeutic ones. The most severe complication was pneumothorax in 10 cases (4%), after 2 out of 150 (1.3%) diagnostic thoracentesis and after 8 out of 95 (8.4%) therapeutic thoracentesis (RR, 95% CI 6.8, 1.41-32.77, p < 0.01). The actuarial risk of pneumothorax after the first, second and fourth therapeutic thoracentesis was 7.7%, 25.3% and 34.7%, respectively. CONCLUSIONS: Diagnostic thoracentesis in cirrhotic patients is associated to a low morbidity. Therapeutic thoracentesis is a risk factor for pneumothorax and the risk increases after consecutive thoracentesis. A chest radiograph is not justified after a diagnostic thoracentesis, but should be done after a therapeutic thoracentesis. PMID- 11767434 TI - Colonic carcinogenesis in vagotomyzed rats. AB - INTRODUCTION: An increased incidence of colorectal cancer (CRC) has been reported in patients with peptic ulcer disease treated with truncal vagotomy. Inhibition of gastric acid output and its hormonal consequence, hypergastrinemia, have been considered risk factors for the development of CRC. The aim of the present study was to determine whether truncal vagotomy increases, in the short (7 days) and long term (120 days), the incidence of CRC in a model of carcinogenesis. MATERIAL AND METHOD: We used 86 Wistar rats distributed in 7 groups to which DMH (1,2 dimethylhydrazine dihydrochloride) was administered for the induction of colon tumors, at doses of 5 and 20 mg/kg of weight. The first three groups were used as control groups; the rats of the four other groups underwent a truncal vagotomy with pyloroplasty and Heller myotomy prior to the administration of DMH. Finally, we compared the incidence of colonic tumors in vagotomized vs non-vagotomized groups receiving the same dose of DMH. RESULTS: In the non-vagotomized rats that received low doses of DMH (5 mg/kg of weight), mortality was 0% and 0% developed cancer as compared to 40% and 0%, respectively, of rats vagotomized 7 days before the administration of DMH and 20% and 0%, respectively, of rats vagotomized 120 days before the administration of DMH. After the administration of high doses of DMH, mortality was 50% and 80% developed cancer as compared to 100% and 0%, respectively, of rats vagotomized 7 days before the administration of DMH and 61.11% and 42.8%, respectively, of rats vagotomized 120 days before the administration of DMH. CONCLUSION: Truncal vagotomy does not increase the incidence of CRC induced by DMH in the rat. PMID- 11767435 TI - Sedation for gastrointestinal endoscopy. Analysis of tolerance and complications. AB - OBJECTIVE: To analyse tolerance and complications in patients undergoing a gastrointestinal endoscopy. PATIENTS AND METHODS: One hundred forty three patients were prospectively studied: 44.8% underwent a diagnostic upper endoscopy; 13.3%, a therapeutic upper endoscopy; 37%, a diagnostic colonoscopy and 4.9%, a therapeutic colonoscopy. Midazolam or midazolam combined with meperidine were used. Tolerance, level of sedation and complications were studied. Chis quare and ratio comparison tests were used for the statistical analysis. P-values less than 0.05 were considered as statistically significant. RESULTS: In the diagnostic upper endoscopy group, tolerance was better with midazolam plus meperidine vs midazolam only (83.8% and 59.3% respectively); p < 0.05. In the therapeutic upper endoscopy group, tolerance was also better when both drugs were combined; p < 0.05. In the diagnostic and therapeutic colonoscopy groups, tolerance was good in 63.5% and 85.7% of patients, respectively. Men had better tolerance for upper endoscopy; p < 0.05. Tolerance was worse in patients under 40 years of age for upper endoscopy; p < 0.05. Mild desaturation occur in 27.3% of patients, being more severe in therapeutic procedures; p < 0.05. CONCLUSIONS: Tolerance was good in a high percentage of patients, and better in men and in patients older than 40 years of age. The main problem is desaturation, that increases in therapeutic procedures. PMID- 11767436 TI - Wireless endoscopy. AB - Wireless endoscopy consists of a small-sized device which allows gastrointestinal tract images to be taken as it physiologically advances along its lumen after being orally ingested. Its primary contribution is the study of small bowel conditions, a gastrointestinal tract segment in which diagnosis difficulties still arise when using current tests, including enteroscopy. Preliminary studies in animals and healthy subjects have revealed data on image quality, sensitivity, specificity, and safety that demonstrate the benefits of this new technique. This review discusses technical aspects, indications and contraindications, as well as studies reported so far on this endoscopic diagnostic procedure. PMID- 11767437 TI - [Late metastasis of hypernephroma of the Vater's ampulla]. PMID- 11767438 TI - [Non-surgical drainage of pancreatic pseudocyst]. PMID- 11767439 TI - [Pseudoneoplastic gastrointestinal amyloidosis]. PMID- 11767440 TI - [Cholestatic hepatitis caused by gemfibrozil]. PMID- 11767441 TI - [Celiac disease and Budd-Chiari syndrome: infrequent association]. PMID- 11767442 TI - [Gastrointestinal infection caused by Mycobacterium avium complex in patients with AIDS]. PMID- 11767443 TI - [The contribution of academician Alexandr Danilovich Nozdrachev to physiology of the autonomic nervous system (on his 70th birthday)]. PMID- 11767444 TI - [Isoproterenol potentiates atrial fibrillation induced by acetylcholine]. AB - A perfusion with normal Tirode solution containing isoproterenol, acetylcholine and their combination into the sinus node artery of the anesthetized open-chest dogs was used to induce atrial fibrillation. The perfusion of isoproterenol, alone, was unable to induce atrial fibrillation, though significantly increased atrial rate. Meanwhile the perfusion of acetylcholine, alone, did induce atrial fibrillation in all animals. The mixed perfusion of isoproterenol and acetylcholine led to decreasing the threshold (minimum) concentration of acetylcholine to induce atrial fibrillation. Herewith, atrial fibrillation appeared at later time from a perfusion start and lasted for more long time. No significant slowing down of sinus rhythm was registered before the initiation of atrial fibrillation. The data suggest that initiation of paroxysmal atrial fibrillation may only be mediated by parasympathetic activity and dependents on a level of adrenergic activity. PMID- 11767445 TI - [Effect of hypothermia on sequence of the ventricle epicardium repolarization in rabbits]. AB - In anaesthetised rabbits at normal body temperature, the earliest ventricles' epicardial recovery occurs at the heart apex and adjacent left ventricle's surface whereas the latest one occurs at the epicardium of the right ventricle's base. A decrease in the mediastinum temperature to 32 degrees C reversed the recovery sequence. Following the cooling of the heart, the longest prolongation of the activation-recovery interval occurred at the heart apex area and the lowest one--at the right ventricle base. PMID- 11767446 TI - [Contractile function of vessel myocytes: dependence on the stretch magnitude]. AB - The values of the optimal stretch for the maximal responses of the rat mesenteric artery ring to electrical field stimulation (FES) or noradrenaline as well as for the maximal myogenic responses, tone, and maximal changes in these responses produced by low pH and dynamic sinusoidal stretch of the vessel wall were compared. The findings show that the magnitude of stretch corresponding to the maximal effect depend on the character of responses, on the factor, and on the responses occurrence conditions. PMID- 11767447 TI - [Reactivity of the arterial system during vasodilation induced by sodium nitroprusside]. AB - A stepwise decrease in the blood pressure by means of sodium nitroprusside infusion led to progressing diminishing of mesatone pressor effects in anaesthetised rats. Cardiac output changes due to mesatone administration did not depend on the initial blood pressure. The latter being lower than physiological limits, a direct linear correlation occurred between pressor responses and shifts of general peripheral resistance, on one hand, and the degree of the blood pressure initial drop, on the other hand. The constrictor responses under study are discussed in respect to their dependence on initial tone of arterial vessels. PMID- 11767448 TI - [Tyrosine hydroxylase expression in differentiating neurons of the rat arcuate nucleus: inhibitory effect of serotoninergic afferents]. AB - In vivo studies, serotonine synthesis in the rat fetal brain was inhibited by p chlorphenylalanine from the 11th to the 20th embryonic day. Serotonine depletion significantly decreased thyrosine hydroxylase content in the neurones of males and females on the 21st embryonic day and in males--on the 35th postnatal day. In vitro, a co-culture of arquate nucleus' and raphe nucleus' embryonic neurones resulted in a sex-specific increase of the thyrosine hydroxylase level in the former neurones. The raphe nucleus' neurones manifested an increased level of serotonine. The findings suggest an activating long-lasting effect of serotonine afferents on the thyrosine hydroxylase expression in differentiating neurones of the arquate nucleus in rats during prenatal ontogenesis. PMID- 11767449 TI - [Characteristics of the rat behavior following single and multiple exposures of the hypoglycemic insulin doses]. AB - Rats behaviour in the "open field" changed in 2 hrs after a single episode of hypoglycaemia was abolished with glucose whereas no changes occurred in their stereotyped behaviour and intraspecies interaction. In 24 hrs quantitative parameters of the "open field" behaviour normalised although the behaviour still had an altered structure. At the same time, amphetamine-induced stereotyped behaviour's indices became reduced. These and other findings suggest some deeper behavioural changes in rats during their recovery from repeated hypoglycaemic episodes and absence of synchronisation of the insulin effects. PMID- 11767450 TI - [Structural and functional changes in sympathetic ganglia following endotoxin and alpha1-antitrypsin exposure]. AB - Structural and functional organisation of sympathetic ganglia under conditions of endotoxemia was studied in white rats, cats, and dogs. Submicroscopic characteristics of the changes occurring in the rat prevertebral sympathetic ganglia after endotoxin administration or application of endogenous proteinase inhibitor alpha 1-antitrypsin, were assessed as well as ultrastructural bases of the febrile rat ganglionic responses to antipyretic drug administration. Effects of endotoxin on synaptic transmission in inferior mesenteric plexus' ganglia of cats and on electrical activity in inferior mesenteric plexus' ganglia of dogs, were electrophysiologically demonstrated. PMID- 11767451 TI - [Changes in the afferent activity of the vagus nerve and the rectal temperature in rats following Escherichia coli endotoxin administration]. AB - In anaesthetised rats, i.p. administration of the Echerichia coli lipopolysaccharide in doses 5 mcg/kg (LPS) increased afferent activity of the cervical vagus, whereas 100 and 1000 mcg/kg doses inhibited the afferent discharges. Pyrogen-free saline (PFS) did not alter the activity. Rectal temperature (RT) was decreased by the PFS and by large doses of the LPS. Sodium salicylate administration prevented the effects. PMID- 11767452 TI - [Structural organization of the nervous system in the wall of the Prosobrancia mollusc mantle cavity and its organs]. AB - Results of comparative investigation into morphological specifics of the receptor and nervous cells and their interrelations in walls of various Prosobranchia molluscs' mantle cavity. Structural specifics and evolutionary regularities of the visceral nervous system's afferent portion in gastropods are discussed. PMID- 11767453 TI - [Activation of the antioxidant system as a factor in increasing the body resistance during combined adaptation]. AB - In semi-aquatic mammals (minks and muskrats) significant changes were found to occur in the leukocyte formula during adaptation to hypoxia, as compared with non adapted rats and mice, although no increase in lipid peroxidation was found in any of their organs. This latter finding seems to be due to simultaneously enhanced activities of superoxide dismutase and catalase. In humans under professional stress, treatment with combined technology of adaptation: cold-and hypoxic exposure, yields a positive therapeutic result accompanied by a decrease in lipid peroxidation and increase in superoxide dismutase and catalase activities in the blood. The data obtained suggest that the strategy of formation of protection against hypoxia and toxic free radical oxidation is common for the animals and humans. PMID- 11767454 TI - [Stress-induced inhibition of the ileal, caecal, and colonic contractile activity in rabbits]. AB - In alert rabbits, immobilisation stress decreased the spike burst rate and amplitude in ileum, caecum, and colon for 20 min. Following beta-adrenoceptor blockade, the contractile activity suppression was aggravated. The stress seems to lead to suppression of the ileal, caecal, and colonic contractile activity for up to 40 min which is unrelated to adrenergic inhibition of the smooth muscle activity mediated by beta-adrenoceptors. PMID- 11767455 TI - [The role of stimulation parameters of sympathetic nerves in regulation of microvessel tone in the rat stomach]. AB - Maximal responses to splanchnic nerve stimulation occurred in rats at the pulse width 0.5-1.0 Ohms regardless of the frequency. Peak constriction of arterioles and venules occurred at a 3-4-sec burst duration and 1-2-sec interval. Adrenergic blockade abolished the vasoconstriction in response to continuous nerve stimulation. However, the responses persisted in high-frequency burst stimulation, suggesting an involvement of non-adrenergic co-transmitter release. Thereupon, an efficient control of microvascular tone can be achieved by grouping the pulses into bursts or by an increase of the burst rate or duration. PMID- 11767456 TI - [Interactions of histamine and glucocorticoids with nerve structures of respiration passages]. AB - Histamine was shown to exert various effects upon respiratory pathway wall's structures in rats. Glucocorticoids were shown to inhibit an increase in intracellular calcium induced by histamine. This investigation involved study of the interaction mechanisms between histamine and dexamethasone, on one hand, and intramural neural structures, on the other hand. PMID- 11767457 TI - [Involvement of pharyngeal muscles in compensatory responses of the respiration system to inspiration resistance load]. AB - The present study was undertaken to test the hypothesis that recruitment of upper airway muscles in loaded breathing is a result of integration of peripheral chemoreceptor and pulmonary mechanoreceptor afferents. Experiments were performed in spontaneously breathing tracheostomized anesthetized rabbits. It had been studied the effects of inspiratory resistive loading to EMG activity of genioglossus muscle. In the intact rabbits the peak value and duration of inspiratory activity of genioglossus increased in loading. Imposition of resistive load in vagotomized animals did not evoke alteration in inspiratory activity of genioglossus in the first loaded breath. Hyperoxia decreased the response of genioglossus muscle to inspiratory loading and vagatomy. We conclude that hypoxic stimulation of peripheral chemoreceptors and decrease in volume related afferent activity from pulmonary stretch receptors are major mechanisms of the upper airway muscle recruiment in inspiratory resistive loading. PMID- 11767458 TI - [Effects of various regimes of rhythmic photostimulation on fatigue and related parameters of the psychophysiological status in humans]. AB - In randomised blind study with active placebo control in humans, rhythmic photostimulation of 77 Hz frequency did not elicit any fatigue or negative psychophysiological events as opposed to 50, 60, 100 Hz frequency. This and other findings are to be considered in designing rational systems of cinema projection and PC monitors. PMID- 11767459 TI - [Interleukin-1beta and depressive states]. AB - Administration of Interleukin-1 beta (IL-1 beta) in pyrogenic and subpyrogenic doses induced a depression of social and exploratory behaviour in rats. A reduction in locomotor activity only occurred with pyrogenic doses of the IL-1 beta. The low dose induced the reduction whereas the high dose the increase of anxiety in elevated plus maze. The opposite effects of two doses of IL-1 beta were observed also in a test with saccharine. PMID- 11767460 TI - Texas medicine. Rounds. HHS to fund UT-San Antonio research on U.S.-Mexico border health care. PMID- 11767461 TI - Prompt pay deja vu. PMID- 11767462 TI - Listening to reason. PMID- 11767463 TI - Bad connection. PMID- 11767464 TI - Remodeling the foundation. Interview by Laurie Stoneham. PMID- 11767465 TI - Extending telemedicine. PMID- 11767466 TI - Alzheimer's disease: recent advances in etiology, diagnosis, and management. AB - Alzheimer's disease is a chronic and progressive neurodegenerative disorder characterized by cognitive and functional deficit and by behavior disturbance. This disease presents a major clinical and social challenge. Increasing evidence suggests that early intervention can delay the progression of the disease and improve symptoms and cognitive functioning. Recent research focuses on genetic susceptibility. Genetic testing may eventually prove to be useful in identifying persons at risk before the onset of symptoms, but at this stage, this testing plays a limited role in identifying and confirming the diagnosis and in genetic counseling. The diagnostic work in all suspected cases of dementia should be started by family physicians; confirmed cases should be treated as soon as possible by the family physician or referred to a psychiatrist or neurologist for appropriate treatment. Donepezil, new cholinesterase inhibitors, and vitamin E have proved effective in delaying progression of Alzheimer's disease. PMID- 11767467 TI - Controversies in professionalism: accepting gifts from patients. PMID- 11767468 TI - [Acoustic impedance of the middle ear and its peculiarities in various forms of acute neurosensory hypoacusis]. AB - Available are the results of impedance audiometry in 250 patients with acute neurosensory hypoacusis (ANH) in different forms. In ANH of traumatic, vascular, pharmacological and infectious etiology tympanogram was normal with registration of the acoustic reflex with high amplitude. The presence of the positive phenomenon of a rapid loudness increase points to impairment of the receptor system of the cochlear analyser. In allergic ANH, motility of the tympanic membrane is abnormal, in spite of the absence of serous liquid in the tympanic cavity and patency of the auditory tube, the acoustic reflex is not registered. PMID- 11767469 TI - [Phasic audiometry in differential diagnosis of sensorineural hearing loss of different etiology]. AB - An original method of differential diagnosis of neurosensory hypoacusis of different etiology is proposed. It is based on registration of the threshold of hearing a short signal moving from 0 degree to 360 degrees against the fluctuation phase of the masking low-frequency tone. In hydrops of the labyrinth phasic audiogram presents as a straight line and demonstrates the lack of auditory thresholds modulation. PMID- 11767470 TI - [Brain stem structures in the acoustic pathways in radiation exposed persons]. AB - Short-latent acoustic evoked potentials were analysed in 163 persons exposed to radiation after the Chernobyl accident regarding their cardiovascular status. Alterations of the brain stem structures of the acoustic analyzer were most pronounced in radiation-exposed persons with cardiovascular diseases. Such alterations were also registered in 50% of radiation-exposed subjects with normal heart activity. PMID- 11767471 TI - [Correction of abnormal hepatic metabolism in sensorineural hypoacusis with photon hemotherapy]. AB - Hepatic metabolism, blood rheology and lipid peroxidation were studied in 160 patients with neurosensory hypoacusis (NSH) at the age of 35 to 74 years. Of them, 63 patients had acute NSH and 97 ones had chronic NSH. Lipid metabolism was involved in the revealed disorders. Photon hemotherapy was effective in correction of hepatic disbolism. PMID- 11767472 TI - [Vestibular function after a reconstructive surgery improving hearing in patients after radical operation on the middle ear]. AB - The study included 62 patients who had undergone radical surgery (RS) on the middle ear. The patients were later operated to improve hearing according to the original reconstructive technique. Before the reconstructive surgery and 1-2, 3 6, 12 and 36 months after it combined vestibulometric examination, otomicroscopy, audiometry assessed the treatment efficiency. Perception of live speech was also investigated. Vestibular dysfunction occurred in 87.1% of the examinees with the history of RS. One of the main causes of the dysfunction was micropathological foci in the trepanation cavity located primarily on the medial wall. Surgical reconstruction creates a closed ventilated neotympanic cavity lined with mucosa. This promotes correction of vestibular dysfunction. Vestibular dysfunction late after radical surgery on the middle ear should be, along with hypoacusis, an indication for reconstructive hearing-improving surgery because the latter relieves or eradicates subjective and objective manifestations of the vestibular dysfunction in many previously operated patients. PMID- 11767473 TI - [Prevention of postoperative scar processes in otorhinolaryngology experimental rationale]. AB - It is shown in vitro that fibroblast proliferation may be inhibited by 5 fluorouracil (5-Fu). In stimulated growth of the fibroblasts the 5-Fu antiproliferative effect takes place even in minimal concentration (2 mcg/ml). Fibroblastic proliferative activity recovers after elimination of 5-Fu from the medium at concentration under 63 mcg/ml. PMID- 11767474 TI - [Immediate short- and long-term results of rehabilitation of children with laryngeal papillomatosis]. AB - The authors review their 30-year experience with rehabilitation of children with laryngeal papillomatosis. A total of 212 patients at the age from 9 months to 15 years have been treated. Immediate, short- and long-term results of different combined surgical and conservative treatments are compared. The authors hold that the papillomatous tissue should be eliminated completely, therefore, during surgery under anesthesia endolaryngeal removal of the papillomas should be combined with monopolar coagulation of their residual tissues. The combined surgery should be immediately followed by etiopathogenetic conservative treatment. The highest effect was achieved with autoserum administration according to the scheme. In combined rehabilitation of such children local etiopathogenetic treatment is preferable. PMID- 11767476 TI - [Perilymphatic fistulas of the labyrinth: diagnostic problems]. AB - Basic diagnostic criteria for perilymphatic fistulas of the labyrinth (PFL) comprise previous trauma or psychoemotional stress, unilateral acute affection of the acoustic and vestibular functions, severe noise in the ears, mixed hypoacusis, lower hearing thresholds in change of the head position, alteration of stabilogram parameters in rising pressure in the external acoustic meatus. PMID- 11767475 TI - [Hemodynamics of nasal mucosa, nasal respiration and mucociliary transport in health and disease]. AB - The method of transillumination rhinography is proposed which provides a graphic image of hemodynamics of nasal mucosa, nasal respiration and mucociliary transport. Changes of the above hemodynamics in different nasal diseases are described. Rhinothermopharmacology is proposed as a new approach to assessment of the known regularities. PMID- 11767477 TI - [Role of non-spore-forming anaerobic microflora in the onset and development of otogenic abscesses of the brain and cerebellum]. AB - The role of non-spore-forming anaerobic microflora in development of otogenic cerebral and cerebellar abscesses was studied in 49 patients with brain abscesses. Microfloral study of the middle ear discharge and content of cerebral abscess demonstrates that at present the role of pathogenic pyogenic staphylococci, streptococci and other kinds of purulent infection is lower than that of previously unreported non-spore-forming anaerobs in the pus of otogenic brain abscesses. It means that urgent sanation of the primary focus and cerebral abscesses should be supplemented with targeted combined antibacterial conservative therapy. PMID- 11767478 TI - [Correction of intranasal structures in nasal septum deformity]. AB - 100 patients with nasal septum deformity were divided into two groups. 50 patients of group 1 have undergone resection of the deformed part of the septum with implantation of the metalloceramic plate. Hyperplastic inferior turbinated bones were exposed to submucous radiowaves. 50 control patients of group 2 have undergone submucous resection of the septum according to Killian. Side effects in group 1 were rare, while long-term functional results were good. PMID- 11767480 TI - [Oto- and rhinosinusogenic sepsis in children]. AB - Clinical characteristics of 25 cases of otogenic and 26 cases of rhinosinusogenic sepsis have been analysed. The main diagnostic criteria of the sepsis were the following: fever, leukocytosis, micro- and macrovascular abnormalities, respiratory and coagulation disorders, abnormal protein levels in plasma, etc. Oto- and rhinosinusogenic sepsis in 45(88.2%) examinees was associated with intracranial complications. Early diagnosis of sepsis, timely operation after adequate preparation, administration of antimicrobial drugs and infusions, stay of patients in intensive care unit with permanent monitoring provided a good outcome in 94% patients. PMID- 11767479 TI - [Ozone therapy in patients with chronic purulent rhinosinusitis]. AB - 102 patients with chronic purulent rhinosinusitis were treated with irrigation of the paranasal sinuses with ozone-oxygen mixture. A total of 5-7 procedures were performed. 30 control patients were treated conventionally. 89% of the study group patients recovered 4.3 days earlier than the controls. PMID- 11767481 TI - [ENT-related diseases in children with hemorrhagic dengue fever]. AB - ENT affections were studied in 100 children with dengue hemorrhagic fever (DHF) admitted to children's hospital in Pnompen (Cambodia). Leading clinical symptoms, changes in laboratory findings, incidence rate and kind of ENT affections are described. PMID- 11767482 TI - [A rare form of congenital laryngeal anomaly: thyro-sternum ligament]. PMID- 11767483 TI - [A case of a breast cancer metastasis to the frontal sinus]. PMID- 11767484 TI - [Pathophysiological mechanisms of chronic inflammatory diseases of the upper respiratory tract mucosa]. PMID- 11767485 TI - [Characteristics of the acoustic reflex in patients with sensorineural hearing loss]. AB - The authors analyse acoustic reflex threshold in 142 patients with neurosensory hypoacusis, describe acoustic invertion in patients with a severe hearing loss (more than 80 dB), suggest causes of the acoustic reflex inversion. PMID- 11767486 TI - Colorectal foreign bodies: a complex medical problem. PMID- 11767487 TI - Colorectal trauma caused by foreign bodies introduced during sexual activity: diagnosis and management. AB - PURPOSE: The aim of this study is to describe 17 cases of colorectal foreign bodies introduced during sexual activity, gathered by the authors over the past twenty years (1980-2000), and to establish diagnostic and therapeutic guidelines for these situations. MATERIAL AND METHODS: A total of 17 patients were treated for rectal trauma caused by foreign bodies due to unusual sexual practice. The extraction of the foreign body was possible through the canal anal in 10 cases using different techniques (gynecological forceps, Foley catheters, etc.), whereas 7 patients required surgical treatment; in five patients a protective colostomy was needed, and in the other two a simple suture of the rectal lesion was performed. RESULTS: There were no deaths and no post-operative complications. In all cases the colostomy was closed 3-6 months after surgery. There were no cases of anal incontinence. CONCLUSIONS: A detailed clinical history and physical examination are essential for the diagnosis and management of these lesions, in addition to any other diagnostic techniques that might be necessary. Great care should be taken when extracting the foreign body so as to avoid its breakage inside the rectum, which would complicate a rather simple problem. PMID- 11767488 TI - Hepatitis C virus infection, increased serum ferritin and hyperinsulinemia. AB - OBJECTIVES: Recent studies have reported a high prevalence of diabetes mellitus in populations infected with Virus C (HCV). The aim of this study is two-fold: a) to support the hypothesis of hyperinsulinemia as a risk factor for developing diabetes in these patients, with a prospective determination of baseline insulinemia in non-diabetic cirrhotic patients infected with HCV, comparing their values with those of a group of non-HCV non-diabetic cirrhotic patients; b) to investigate in both groups the factors associated to increased peripheral resistance to insulin. MATERIAL AND METHODS: Thirty two HCV cirrhotic diabetic patients (group I) and 41 non-diabetic cirrhotic patients of other etiologies (group II) participated in the study. Baseline insulinemia, as well as factors related to insulin resistance such as age, anthropometric indexes, stage of cirrhosis development using the Child-Pugh index, serum ferritin and treatment with insulin resistance inducing drugs were compared in both groups. RESULTS: Average baseline insulinemia in group I was 21.5 mU/ml (18.6-24.4), vs 14 mU/ml (10-18) in group II (p < 0.001), and the percentage of hyperinsulinemia was 87.5% (72.5-95.9) vs 56.1% (40.8-70.6), respectively (p < 0.01). No differences were observed between the two groups when comparing the following variables: age [54.4 (48.3-60.6) vs 59.9 (56.3-62.7) years of age, NS], weight [72.9 (69.5-76.3) vs 74.2 (70.8-77.7) kg, NS], height [163.6 (160.5-166.7) vs 161.3 (159.4-163.2)] cm, NS], body mass index [27.6 (26.1-29.1) vs 28.4 (27.3-29.5) kg/m2 of height, NS]; and Child-Pugh staging score (A: 31 vs 27; B: 0 vs 7; C: 1 vs 7, NS). However, serum ferritin levels in group I patients were higher than those in Group II [123.3 (12.4-289.3) vs 65.5 (2.4-306) ng/ml, p < 0.05]. It must be considered that at the recruitment 3 patients in Group I were taking either diuretics or non selective beta-adrenergic blockers, compared to 14 patients in Group II, p < 0.01. Finally, the multivariate logistic regression analysis showed that insulinemia values (OR = 1.21; CI 95% 1.09-1.34, p < 0.001) and ferritin levels (OR = 1.21; CI 95% 1.02-2.69, p < 0.04) were independent variables associated to HCV infection. CONCLUSIONS: HCV-positive non-diabetic cirrhotic patients have higher baseline insulinemia levels and increased prevalence of hyperinsulinemia than cirrhosis due to other etiologies. This could be explained by an increase of peripheral insulin resistance, mediated by the increase of iron deposits in these patients, and could be responsible for the increased risk of developing diabetes mellitus. PMID- 11767489 TI - Complications of colonic diverticular disease. Comparative study of two series. AB - OBJECTIVE: To compare the form of presentation and management of the disease in two surgical units covering geographically different populations. DESIGN: Observational retrospective study. PATIENTS AND METHOD: 203 cases from the 2nd Chair of Surgery of the Hospital Universitario de Clinicas de Asuncion, Paraguay and 150 cases from the Hospital Universitario de Lleida, Spain. We analyzed the cause of admission, medical history, treatment and post-operative morbidity and mortality. RESULTS: Paraguay series: average age: 53 years (range 34-84) for men and 62 years (range 36-92) for women. Fifty-five per cent were hospitalized because of hemorrhagic complications and 45% because of acute diverticulitis. Medical treatment was provided in 109 cases and surgery in 110, 72 of which were emergencies and 38 elective procedures (p < 0.05). Morbidity was 31.8% (40.2% in emergencies and 16% in elective procedures, p < 0.05) and mortality was 15.5% (20.2% in emergencies and 2.6% in elective procedures, p < 0.003). LLEIDA SERIES: Average age: 65.5 years (range 38-85, p < 0.01) for men and 71.4 years (range 30 93, p < 0.01) for women. Eighty-six per cent were hospitalized because of acute diverticulitis and 10.7% because of acute hemorrhage (p < 0.001). Sixteen per cent have had previous attacks (p < 0.001). Medical treatment was provided to 111 patients and surgery to 39 (p < 0.001), 33 of which were emergencies and 6 elective procedures (p < 0.04). Morbidity was 41% and mortality 12.8% (5 cases), all of which were emergencies. The surgical technique was similar in both groups: resection with primary anastomosis in elective procedures and Hartmann's procedure in most emergencies, with a rate of immediate anastomosis of 33 and 21%, respectively. CONCLUSIONS: Factors related to nutrition and quality of life may influence the development of diverticular disease. Emergency surgery should be prevented. Surgeons must adapt their surgical approach to the socioeconomic and cultural medium of the population. PMID- 11767490 TI - Use of recombinant factor VII in hepatology. AB - Understanding the key role of factor VII (FVII) in the cascade of blood coagulation has led to consider its administration as an effective treatment for selected situations with altered haemostasis. Advances in genetic engineering have made it possible to obtain this factor by recombinant techniques (rFVII), rendering it both safe and widely available as a haemostatic treatment. So far, it has been commonly used for haemophilic patients with inhibiting antibodies against factors FVIII-FIX, but its use is currently extending to other areas. The presence of decreased FVII levels in patients with advanced, chronic liver disease has recently raised an interest in the study of this molecule as a new therapeutic option in the field of Hepatology. This paper will discuss the characteristics, indications, and studies existing to this day on the use of rFVII, particularly in cirrhotic patients. PMID- 11767491 TI - [Abdominal pulmonary actinomycosis mimicking colonic tumor with lung and liver metastases]. PMID- 11767492 TI - [Tropical sprue as unusual cause of chronic diarrhea]. PMID- 11767493 TI - [Erysipeloid skin metastasis as presentation form of gastric cancer]. PMID- 11767494 TI - [Non-functioning retroperitoneal paraganglioma. Clinical case]. PMID- 11767495 TI - A case of bleeding gastric varices treated with recombinant factor VII. PMID- 11767496 TI - [Roentgenomorphological correlations in the diagnosis of pneumonias in patients with combined, craniocerebral, thermal injury and exogenous poisonings]. AB - The clinical roentgenological and postmortem morphological data were analyzed and correlated in 219 patients with combined (60), craniocerebral (38), thermal (46) injury and exogenous poisonings (75), who developed pneumonias in the course of the treatment. All the patients underwent chest roentgenography in the anteroposterior projection and in the supine position. The rate of intravital identification of pneumonias accounted for 73.3% in combined, 63% in craniocerebral, 65.2% in thermal injury, and for 77.3% in exogenous poisonings. The roentgenological and morphological characteristics common to the development of pneumonias in different injuries were revealed and the causes of diagnostic discrepancies were analyzed. PMID- 11767497 TI - [SPECT and MRT in the diagnosis of myocarditis of mild and moderate severity]. AB - Technetium-99mWBC SPECT and contrast material enhanced MRI were used for the diagnostics of mild myocarditis. The use of labeled leukocytes and paramagnetic contrast agent allow visualizing inflammation of myocardium and assessing the efficacy of treatment. 49 patients aged 14 to 49 years old were studied. Case presentation demonstrates high information and diagnostic value of used methods. PMID- 11767498 TI - [Quantification of physiological kyphosis adults according to the roentgenogramometry data]. AB - The shape of thoracic physiological kyphosis was studied based on data obtained through the examination of 120 patients who had presented no complaints regarding thoracic spine. As a result, a quantitative description of a normal curvature for thoracic kyphosis was elaborated. The study addressed such issues as the impact of separate segments on the development of kyphosis, with the identification of relevant quantitative parameters. In addition, sex-related differences of the quantitative parameters describing the form of thoracic spine were determined. The study analyzed tendencies in the curvature transformation during the life period of 16-30 years of age. PMID- 11767499 TI - [Current x-ray diagnosis of Crohn's disease of the small intestine]. AB - The paper evaluates the potential for x-ray diagnosis of Crohn's disease of the small intestine in 18 patients using the new barium contrast medium Entero-VU intended for examination of the small intestine. The authors provide a detailed description of the examination technique, x-ray appearance of Crohn's disease and make a comparative analysis of the diagnostic potential for the use of the common barium suspension and the contrast agent Entero-VU. The cases of Crohn's disease analyzed in the paper encompass its different stages and sites in the small intestine. The group of patients presenting with Crohn's disease accrued subjects who had undergone surgical treatment followed by reexamination of the small intestine using Entero-VU. According to the authors, the new barium contrast medium Entero-VU intended for small intestine examination possesses two basic advantages: simplicity of examination and high diagnostic efficacy. PMID- 11767500 TI - [Computed tomography of the temporal bones in children with developmental anomalies of the external and middle ear]. AB - Computed polypositional high-resolution tomography (CT) was provided to 45 children with dysplasia of the external acoustic meatus (EAM). The computed tomograms were analyzed in accordance with the scheme which included the evaluation of the following structures: atresia or stenosis area, pneumatized mastoid process, tympanic cavity, ant rum, osteal opening of the Eustachian tube, chain of auditory ossicles, windows of the labyrinth, internal ear, facial nerve canal, and large vessels. Preoperative CT of the temporal bones allows for the evaluation of the above-listed structures, which is of paramount importance for the planning of the patient management policy. Also, CT enables the assessment of the risk of surgical intervention associated with a potential injury to the facial nerve, large vessels, and temporomandibular articulation. CT is to be an indispensable diagnostic modality for examination of children presenting with EAM dysplasia. PMID- 11767501 TI - [X-ray diagnosis of the adrenal neoplasms]. PMID- 11767502 TI - [Cases of the diagnosis of submucous gastric tumor by spiral x-ray computed tomography]. PMID- 11767503 TI - [Techniques of the roentgeno-radionuclide diagnosis of lung sarcoidosis]. PMID- 11767504 TI - [Semiotics of lesions of the cerebral venous collectors on application of noninvasive techniques of x-ray diagnosis]. AB - The study included application of a complex of the noninvasive diagnostic techniques such as MR tomography, MR venography, duplex scanning of the internal jugular veins, and transcranial Doppler sonography. The authors provide a detailed description of the semiotics of the MR signs of cerebral venous collector lesion in patients with thrombosis, extravasal compression, aneurysms, and developmental anomalies. Present the quantitative ultrasound parameters of hemodynamics in the efferent vessels of the brain accessible to inspections describe the effect of spontaneous echo-opacification in the internal jugular veins, which is assumed to be a predictor of thrombosis. Intravenous injection of magnevist resulted in an appreciable refinement of visualization of small dural sinuses at MR venography thereby allowing for the diagnosis of their thrombosis. It is suggested that the use of the entire complex of the x-ray modalities under consideration may lead to a more complete and noninvasive evaluation of the nature of cerebral venous insufficiency and of the degree of hemodynamic significance. Moreover, this will make it possible to outline approaches to therapeutic or surgical correction of the disease. PMID- 11767505 TI - Child's play. PMID- 11767506 TI - Assessment of children with pervasive developmental disorders. AB - TOPIC: Pervasive developmental disorders, a group of conditions marked by impaired social reciprocity, communication deficits, and restricted, repetitive behaviors. PURPOSE: Advanced practice nurses (APNs) are in a unique position to assess these children, make appropriate diagnoses, and refer parents for further consultation and intervention. SOURCES: Current literature, formal training on diagnostic instruments, and clinical experience. CONCLUSIONS: Diagnosis of pervasive developmental disorders requires knowledge of normal growth and development and other childhood psychiatric disorders. The role of the APN includes counseling parents regarding their child's legal right to intervention and guiding parents to make empirically based choices for intervention. PMID- 11767507 TI - Developing and implementing a comprehensive program for children and adolescents with eating disorders. AB - TOPIC: Treatment of eating disorders in children and adolescents across a continuum of care. PURPOSE: To describe the development and implementation of a comprehensive pilot program for children and adolescents with eating disorders. SOURCES: Published literature and clinical experience. CONCLUSIONS: The pilot program to provide comprehensive care to children and adolescents has been successful. As of November 2000, the inpatient modal eating disorder census has been 4 (highest = 10, lowest = 1). With the focus on prevention and early intervention, the multidisciplinary team continues to educate the public and providers. PMID- 11767509 TI - The use of seclusion is not evidence-based practice. AB - TOPIC: Published articles on the use of seclusion in psychiatric care. PURPOSE: To present the argument that the use of seclusion in the psychiatric care of children is not evidence-based practice. SOURCES: Review of the scientific study literature of the last 30 years on the use of seclusion. CONCLUSIONS: The scientific evidence available illustrates that the use of seclusion with children is not therapeutic and is, in fact, harmful to patients. PMID- 11767508 TI - Medical fears following alleged child abuse. AB - PROBLEM: This study profiled children's and adult guardians' pediatric anogenital exam worries. METHODS: Forty-seven girls (mean = 11.57, SD = 2.14) and their guardians rated their anticipatory exam worries in a pediatric clinic setting. RESULTS: A substantial minority of children reported elevated concern about their lack of exam knowledge, the staff's unfamiliarity, someone inspecting their private parts, and their health. Most adults reported elevated concern about their lack of exam knowledge and their children's health. A substantial minority of adults also reported elevated concern about their children's distress and the exam's potential painfulness. Child's age but not prior exam experience was correlated with some of these concerns. CONCLUSIONS: Participants approached the exam with specific concerns. These data may inform interventions aimed at minimizing distress and facilitating adjustment. PMID- 11767510 TI - Culture bound. A closer look at three documents. PMID- 11767511 TI - A national action agenda for children's mental health. PMID- 11767512 TI - [Application of competition index in assessing intraspecific and interspecific spatial relations between manchurian ash and dahurian larch]. AB - The competition among trees within a stand includes aboveground and underground parts. How to determine the zone of competition influence is important for predicting tree growth. We divide the zone into two parts: one part is defined as inside radius, the distance from nearest competitors to subject tree, in which, the competition influence is the sum of both aboveground and underground; the another part is defined as outside radius, the distance of competitors to subject tree, where the competition influence comes mostly from underground. Thus, the competition index, based upon the divided two radii, could be decomposed into different components. We used the data of manchurian ash(MA) (Fraxinus mandshurica) and dahurian larch(DL) (Larix gmelini) from pure and mixed stands to analyze the competition influence of aboveground and underground in inside and of underground in outside radius. The results show that for MA in pure stand, the competition effect was 59.06% from inside radius, and 40.94% from outside radius. For DL in pure stand, the competition effects in both radii were 71.31% and 28.69%, respectively. There was a stronger competition influence in inside than in outside radius. Underground competitions were the important issues for both species in pure stands. In a mixed stand of MA and DL, there were two species in both radii, and the effects of competition came from intraspecific and interspecific competitors. For subject tree of MA, the effect of interspecific competition was 49.55%, and that of intraspecific was 50.45%. For subject tree of DL, the effects were 81.11% and 18.89%, respectively. DL displayed a stronger interspecific competition than MA in the zone of competition influence, and was a main effect of competition on MA. For subject tree of MA, the effect of competition from inside radius was 25.33%, which was the sum of competition influence from aboveground and underground, and about 74.67% was from outside radius. For subject tree of DL, both in inside and outside radii were 55.37% and 44.64%, respectively. Comparing with the information from both species and two radii, the root-root competition from underground was an important component. DL grew well, and could reduce the impact of intraspecific competition for MA when both species mixed in a stand. PMID- 11767513 TI - [Individual tree growth-competition model in mixed plantation of manchurian ash and dahurian larch]. AB - Based on distance-dependent competition models and neighborhood interference models, the competition index components and competition effect coefficients were used to quantify the spatial competition among trees in the mixed plantation of ash(Fraxinus mandshurica) and larch(Larix gmelini). Taking each component of competition index as independent variables and the yearly volume growth as dependent variable, the competition-growth model was established with good regression result. The study provided a new approach to deal with the further improvement of spatial competition models and the plant competition-growth relationship ecological study. PMID- 11767514 TI - [Bioproductivity of Castanopsis hysrix-Cyclobalanopsis glauca-Machilus pauhoi community in Huitong, Hunan]. AB - Based on the mean DBH measurements of sample trees, the bioproductivity of subtropical Castanopsis hysrix-Cyclobalanopsis glauca-Machilus pauhoi community in Huitong, Hunan province was studied by regression analysis (y = a(D2.H)b). The results showed that the total biomass of the forest was 451.02 t.hm-2, and the component biomass of tree, shrub, liana and litter layer was 426.76, 17.76, 1.80 and 4.70 t.hm-2, respectively. The net production and average production of tree layer were 34.46 and 13.32 t.hm-2.yr-1, respectively. PMID- 11767515 TI - [Neural network based on modified simplex method and its application in studying forest self-thinning]. AB - The mechanism of forest self-thinning is generally nonlinear and dynamic, and the artificial neural network has the characteristic of expressing arbitrary nonlinear mapping. In this paper, the feasibility and limitation of artificial neural network used to simulating forest self-thinning was expounded, and the principle and algorithms of the neural network model based on modified simplex method (BP-MSM mixed algorithms) for modeling forest self-thinning were described. Its applications in self-thinning of Populus tremula natural forest Cunninghamia lanceolata plantation were illustrated. The results of forest self thinning examples show the BP-MSM mixed algorithms were satisfactory in simulating forest self-thinning, and its precision was higher, which develops the method and theory of artificial neural network, and enriches the simulating method of forest self-thinning. PMID- 11767516 TI - [Effect of far-ultraviolet radiation on lipid peroxidation and inherent protection system in seedlings of Taxus cuspidata]. AB - The effect of far-ultraviolet radiation on lipid peroxidation and inherent protection system in seedlings of Taxus cuspidata was examined with simulated UV BC irradiation treatments. The electrolyte leakage, lipid peroxidation, tissue autoxidation and H2O2 content increased, while the contents of soluble protein, ascorbic acid, carotenoids, and chlorophyll and the photosynthetic electron transport rate of Photosystem II decreased with the increasing time of treatment. The lipid peroxidation of the needles was inhibited by exogenous scavengers sodium benzoate and ascorbate, but enhanced to some extent by methyl viologen and DDC (an inhibitor of SOD). The mechanisms of the injury of the seedlings induced by UV-BC radiation might be similar to that of photooxidation injuries of conifers in winter. However, Taxus cuspidata was much more resistant to UV-BC radiation than crops. PMID- 11767517 TI - [Effect of different nitrogen forms on growth of Fraxinus mandshurica seedlings]. AB - The effect of NO3(-)-N and NH4(+)-N and their different supply ratios on the growth of Fraxinus mandshurica seedlings was studied by sand culture in greenhouse. The highest seedling growth was obtained at a NH3(-)-N/NH4(+)-N ratio of 75/25 in nutrient solution. The growth of seedlings declined with the increasing ratio of NH4(+)-N to NO3(-)-N. Excessive NH4(+)-N inhibited root growth, and the root/shoot ratio of the seedlings significantly decreased as the NH4(+)-N/NO3(-)-N ratio was over 50%. Increasing NH4(+)-N in nutrient solution led to the decrease of net photosynthetic rate, the increase of phosphorus content in plant tissues, and the decrease of Zn and Fe contents. The pH value of cultural medium was affected markedly by nitrogen form, which was increased with increasing NO3(-)-N and decreased with increasing NH4(+)-N in nutrient solution. The pH value was up to 7.22 in the medium contained NO3(-)-N alone, while decreased to 4.20 only with NH4(+)-N. PMID- 11767518 TI - [Utilization of insoluble phosphate by Larix gmelini seedlings under phosphorus starvation]. AB - The utilization of insoluble phosphate by 2 years old larch(Larix gmelini) seedlings was studied in greenhouse. The seedlings were grown in sand and AlPO4 was supplied as a source of P. The results showed that larch seedlings could utilize some amount of AlPO4. Supplied with AlPO4 but not incubated with mycorrhizal-fungi, the seedlings could absorb 35.1% and 64.9% of the phosphorus uptake when supplied with soluble phosphate. The effects of various mycorrhizal fungi on utilization of phosphate were different, i.e., the utilization rate of AlPO4 was higher when incubated with Suillus granulatus, but was similar to control when incubated with Suillus grevillei. The proportion of root/crown became higher under P-starvation, and larch seedlings could gain more P by enlarging their root growth. PMID- 11767519 TI - [Rainfall interception capacity of forest canopy between two different stands]. AB - Based on the observation data, the rainfall interception capacity of the canopy in plantation and natural forest stands and its relation to rainfall were examined using the method of taking maximum under the same rainfall. The results showed that the rainfall interception capacity of plantation forest increased rapidly with the increase of rainfall, because of its even distribution of branches and leaves, which was higher under low rainfall less than 30 mm, and the saturation interception capacity was easily reached, depending on the quantity of branches and leaves in the canopy. Although the interception capacity of natural forest was relatively weak under low rainfall less than 30 mm, compared with plantation forest, it was much stronger under heavy rainfall more than 30 mm. The saturation interception of natural forest was larger than that of plantation forest. PMID- 11767521 TI - [Ordination analysis on relationship between bryophyte distribution and climatic factors]. AB - Based on the data of climate and bryoflora in 21 mountainous regions of China, 61 moss families, 23 genera of Dicranaceae, 17 species of genus Campylopus and 35 species of genus Dicranum were analyzed by Canonical Correspond Analysis(CCA) and Detrended Canonical Correspond Analysis (DDCA) to reveal their distribution relationships with nine climatic factors, including annual average temperature, January average temperature, July average temperature, annual average rainfall, annual average fog days, annual average frost days and annual average light hours. The similarity of geographical elements among nine mountains in China and their relationships with climatic factors were also analyzed. The methods of applying DDCA and CCA to analyze the relationships between bryophyte and climatic factors were thus introduced. The studies indicate that CCA and DCCA are applicable in florology and phytogeography. PMID- 11767520 TI - [Effect of elevated CO2 concentration on growth of dominant tree species in pine broadleaf forest of Changbai mountain]. AB - Potted saplings of Pinus koraiensis, Picea koraiensis, Larix olgensis, Populus ussuriensis, Betula platyphylla, Tilia amurensis, Traxinus mandshurica, and Acer mono, the eight dominant species in the Korean pine broadleaf forest at Changbai Mountain, were grown in open-top chambers with ambient(400 microliters.L-1) and elevated (700 microliters.L-1) CO2 concentration under natural sunlight for two growing seasons. The average height growth of these eight species under elevated CO2 increased by 10%-40%, compared with the control at ambient CO2. The response of transpiratory rate to the higher CO2 concentration was different among the species, and the water use efficiency of the saplings of the 8 species growing under elevated CO2 concentration was higher than that under ambient CO2. Soluble sugar and chlorophyll contents were not related to the CO2 concentration under which the saplings grew, indicating that the complicacy was existed in the acclimation of tree species to high CO2 concentration. The response of broad leaved tree species to the elevated CO2 concentration was more sensitive than that of conifer tree species. Saplings of all tree species showed a photosynthetic acclimation to higher CO2 under long-term elevated CO2 concentration. PMID- 11767522 TI - [Net photosynthetic rate of two species of wintering host mosses for gullaphids and its response to light, temperature and water content]. AB - The net photosynthesis of Thuidium cymbifolium and Chrysocladium retrorsum, two species of wintering host mosses for gullaphids, and its response to light, temperature and water content were measured with CI-301PS(CID Inc. USA) both in winter and spring. The photosynthetic capacity of Thuidium cymbifolium and Chrysocladium retrorsum was about 141 and 117 mumolCO2kg-1dw.s-1, respectively, and trended to increase from winter to spring. The light saturation point of these two mosses at 800-900 mumol.m-2.s-1 was much higher than that of many other mosses, and the compensation point ranged from 40 to 50 mumol.m-2.s-1. The temperature response curves of these two mosses were similar, with optium temperature ranging from 25 to 36 degrees C in spring, and from 20 to 30 degrees C in winter. When the temperature was below the freezing point(-15 to 0 degree C), they both maintained a distinct net photosynthesis, with the optimum water content ranging from 200 to 300(400)% dw. The photosynthesis started to be restrained evidently, when the water content declined to about 150% dw. The gas exchange ceased or became negative, when the water content was as low as 40-50% dw. It can be inferred that these two species might be both poikilothermal and poikilohydric organisms, but the resistibility of T. cymbifolium to intense light and high temperature was higher than that of C. retrorsum. PMID- 11767523 TI - [Accumulation of ABA and ODAP in Lathyrus sativus under water stress]. AB - The roots of fifteen days old Lathyrus sativus seedlings were treated by PEG, PEG + ABA and ABA, and their leaves were sampled to determine the contents of endogenic ABA, ODAP, MDA and H2O2 and the activity of superoxide dismutase, catalase, peroxidase and glutathione reductase. The results showed that after treated, the contents of ABA and ODAP in leaves increased markedly. The addition of exogenous ABA decreased the increment of MDA and H2O2 contents and retarded the attenuation of CAT activity, which were induced by PEG stress, and enhanced the GR activity. In addition, when materials were treated with exogenous ABA in a long time, the ABA content in leaves was increased markedly, and ODAP was then accumulated. There was no significant effect on metabolism of active oxygen in the early days(0-3 days) of ABA treatment, but the activities of SOD, POD, CAT and GR decreased, and the contents of MDA and H2O2 increased in leaves of Lathyrus sativus with the duration of ABA treatment(7-15 days). The results indicated that ABA could promote the accumulation of ODAP in leaves of Lathyrus sativus. PMID- 11767524 TI - [Effect of magnetic field on peroxidase activation and isozyme in Leymus chinensis]. AB - This paper studied the effect of extra magnetic field and saline-alkali stress on the seedling growth of Leymus chinensis. The results showed that magnetic field treatment not only improved the seedling growth of L. chinensis, but also enhanced its saline-alkali tolerance. This treatment also increased its peroxidase(POD) activity, and induced an extra POD isozymic band on electropherogram. According to a comprehensive analysis, 300 mT and 200 mT for 10 minutes were determined as the optimum magnetic field intensity on L. chinensis seeds. PMID- 11767525 TI - [Qingshishan watershed agro-ecology information system and its application with the support of Geographic Information System (GIS)]. AB - Geographic Information System(GIS) is applied to establish Qingshishan Watershed Agro-Ecology Information System (QWAEIS), QWAEIS integrates spatial information such as land use, soil, water and topography with basic information such as population, climate and agricultural production. The watershed agro-ecology information was effectively analyzed and managed by QWAEIS, land suitable classes were evaluated by QWAEIS and the land evaluation result are given, QWAEIS also can support watershed planning with its spatial information. PMID- 11767526 TI - [N cycle of rubber-tea-chicken agro-forestry model in tropical area of China]. AB - The N cycle of rubber-tea-chicken eco-agricultural model, a typical tropical agro forestry system in Wenchang municipality of Hainan province, was studied with quantitative experiment and qualitative analysis, compared with rubber and rubeer tea systems. The results showed that the N cycling rate, N output and soil surplus N of chicken garden were all the highest, being 43%; 196.5% kg.hm-2 and 237.6 kg.hm-2, respectively. The N output/input rate of chicken sub-system was 91%, and the transformation rate was very high. Compared with the other two systems, the chicken garden had a decreased external N input rate, and its internal cycling N was the highest, being 824.1 kg.hm-2. Rubber-tea-chicken agro forestry system had a rational N cycling structure, and its N cycle was most active. PMID- 11767527 TI - [Influence of genetic background of photoperiodic response on expression of short photoperiod sensitive male sterility in rice]. AB - The photoperiodic response of F1 and its parents was analyzed, and the photoperiodic response and short photoperiod sensitive male sterility of F2 progenies were studied in this paper. The results showed that the strong response was dominant over the weak response to photoperiod. The photoperiodic response of plants with short photoperiod sensitive male sterility in F2 was above medial degree(the rate of heading acceleration > 15%). Photoperiodic response showed a positive correlation with short photoperiod sensitive male sterility. The main sterility genes of Yid1s and Yid2s were allelism. It can be inferred that the short photoperiod sensitive male sterile gene might be expressed upon the presence of the photoperiodic response genes, and that the short photoperiod sensitive male sterility of plants with the same genes could differ in their reproductive expressions, not because of the changes of the genes, but the difference in genetic backgrounds of photoperiodic response. PMID- 11767528 TI - [Effect of different fertilizer combinations on water supply-demand status of winter wheat]. AB - The soil water status during various growing stages of winter wheat and the effect of different fertilizer combinations on its yield and water use efficiency (WUE) were studied in a semihumid and slanting drought area by using the design of D-optimum saturation. According to water balance law, soil water supply was obviously different with different fertilizer combinations, reaching a peak when N and P fertilizers were combined applied with organic fertilizer, accounting for 27% of total water consumption. N fertilizer added alone took up 100% of total water consumption from rainfall. Water deficiency was most severe when N fertilizer was applied alone, but was the smallest when P fertilizer was applied with organic fertilizer. The combination of N, P and organic fertilizer could significantly improve winter wheat yield and its WUE. PMID- 11767529 TI - [Response of wheat seedlings with different drought resistance to water deficiency and NaCl stresses]. AB - The growth, photosynthesis, transpiration and antioxidative defence system of the seedlings of drought-tolerant wheat strain 8139 and drought-sensitive strain Ganmai No. 8 at 20% PEG 6000 and 1.2% NaCl stresses were compared. The results showed that strain 8139 had a strong drought resistance, but a weak salt resistance. The root growth of both wheat strains was inhibited significantly under salt stress, but stimulated slightly under drought stress. The net photosynthetic rate and water use efficiency of strain 8139 were significantly different from those of Ganmai No. 8 at every stage under both drought and salt stresses, and its transpiration rate was significantly different from that of Ganmai No. 8 only at 7th and 14th day after being stressed. The MDA content in strain 8139 after being stressed for 7 days was much lower than that in Ganmai No. 8 under drought stress, but there was no significant difference between the two strains under NaCl stress. Correspondingly, there was no significant difference in the fructan content and SOD and APX activities between strain 8139 and Ganmai No. 8, but a significant difference in GSH content was found under salt stress. Under drought stress, the contents of fructan and GSH and the activities of SOD and APX in strain 8139 were much higher than those in Ganmai No. 8 at different stage, and strain 8139 exhibited a strong antioxidative defence ability. PMID- 11767530 TI - [Effect of waterlogging on senescence of winter wheat root system at booting stage]. AB - By applying 3 winter wheat cultivars of different water-resistance, the effect of waterlogging at booting stage on the growth and development of root system, 32P absorption and its distribution, and senescence of root system was studied with soil column culture. Waterlogging at booting stage reduced root dry weight, its activity and SOD activity, and increased the relative permeability of plasma membrane and the membrane-lipid preoxidation level(MDA content) of root system. Meanwhile, waterlogging influenced the 32P absorption, transportation and distribution, and consequently, speeded up the senescence of root system. PMID- 11767531 TI - [Effect of mixing seed with fulvic acid on spring wheat yield and its water use efficiency]. AB - Four treatments were installed to study the effect of seed mixed with fulvic acid on sring wheat yield and water use efficiency: CK(without any treatment of fulvic acid); FA(seeds were mixed with fulvic acid before sowing), WM(pre-sowing irrigation of 30 mm plus clear plastic film mulch), and WMFA(pre-sowing irrigation of 30 mm plus plastic film mulch, and seeds were mixed with fulvic acid before sowing). The plastic film mulches in WM and WMFA treatments were removed after sowing for 62 days. Compared to treatment CK, the spring wheat in FA treatment grew more roots and absorbed more water from soil, and increased the spike weight and grain weight per spike and harvest index, which resulted in a higher yield and higher water use efficiency. There was no differenece in water consumption between treatments WM and WMFA, but in treatment WMFA, more dry matter was distributed in shoots, and hence yield and water use efficiency were improved significantly. The yields for the four treatments CK, FA, WM, WMFA were 917.7, 1275.1, 1269.4, 1737.1 kg.hm-2, respectively; and the water use efficiencies were 6.58, 7.85, 6.20, 9.05 kg.hm-2.mm-1, respectively. PMID- 11767532 TI - [Effect of foliar leaching on growth and mineral nutrition of maize under NaCl stress]. AB - The impact of foliar leaching on growth and mineral nutrition maize under NaCl stress was investigated. The results showed that there was no difference in biomass between leaching and control treatments under low NaCl stress (0 and 50 mmol.L-1), but under high NaCl stress (100 and 200 mmol.L-1), the biomass of leaching treatment was higher, with a better at pH 3.5 than at pH 7.0. The shoot K+ content in leaching treatments was higher than that of control under no NaCl stress, but lower under 200 mmol.L-1 NaCl stress. Shoot Na+ content of leaching treatments was lower than that of control under high NaCl stress, and shoot Ca2+ and Mg2+ contents of leaching treatments were higher under no NaCl stress. Root K+, Na+, Ca2+ and Mg2+ content and relative water content of leaching treatments had no significant changes, compared with those of control. It was suggested that foliar leaching could alleviate harmful degree of maize under serious salt stress, which was related with the decrease of shoot Na+ content by foliar leaching. PMID- 11767533 TI - [Aluminum forms in acid sulfate soils]. AB - With the method of sequential extraction, the extractable noncrystalline aluminum in Acid Sulfate Soils was fractionized into exchangeable Al (ExAl), absorbed inorganic hydroxy-Al(HyAl), organic complexed Al(OrAl), Fe oxide bound Al (DCBAl), interlayered Al(InAl) and noncrystalline aluminosilicate(NcAl) with average of 1.79, 2.51, 4.17, 4.14, 4.31 and 8.66 g Al2O3.kg-1, respectively. In actual Acid Sulfate Soils, the amount of different forms Al followed the order of NcAl > OrAl > InAl > DCBAl > ExAl > HyAl, but in potential acid sulfate soils, NcAl > InAl > DCBAl > HyAl > OrAl > ExAl. The average of the total extractable noncrystalline Al was 35.57 g Al2O3.kg-1, which covered 25.04% of the total amount of Al in Acid Sulfate Soils. The characteristic of extractable noncrystalline Al in Acid Sulfate Soils was the high proportion of active aluminum, such as ExAl, HyAl and OrAl. All forms of Al were closely related to the corresponding properties and ecological characteristics of Acid Sulfate Soils. The strong acid environment of actual Acid Sulfate Soils induced over released Al, which transformed to active Al and resulted in Al toxicity. PMID- 11767534 TI - [Continuous cropping obstacle and rhizospheric microecology. III. Soil phenolic acids and their biological effect]. AB - The contents of phenolic acids in the extracts of soil and roots of continuously cropped for five years and normally cropped soybean in Heilongjiang province and their biological effects were studied with HPLC method. The result showed that the contents of p-hydroxy benzoic acid, vanillic acid(extracted by 1 mol.L-1 NaOH) in continuous cropping soil were significant higher than that in normal cropping soil, and the content of vanillin had no significant difference in these soils. The contents of p-hydroxybenzoic acid, vanillic acid, vanillin, ferulic acids, and coumarin of aqueous extracts of soyhean roots were higher in continuous cropping than in normal cropping soil. The activity of polyphenol oxidase in continuous cropping soil was higher than in normal cropping soil. Under conditions of water culture and adding exogenous p-hydroxybenzoic acid, the aqueous extract of soybean roots inhibited the growth of soybean seedlings. After a week of exogenous phenolic acids addition, the residual rates of p hydroxybenzoic acid, vanillic acid, vanillin, benzoic acid, ferulic acids, and coumarin were 10.4%, 15.3%, 4.1%, 2.3%, 5.2%, 17.5%, respectively. There was a very significant exponential relationship between the addition amount of exogenous phenolic acids and the fungi population in soil. PMID- 11767535 TI - [Tolerance of various geographic populations of brown planthopper to adverse environmental stresses]. AB - The populations of brown planthopper(BPH), Nilaparvata lugens, were collected from Zhejiang, Guangxi and Yunnan provinces to study their tolerance to various adverse environmental stresses. The results indicated that all of these three populations could adapt to the rice variety IR26 bearing resistant gene 1 (Bph1), and Guangxi and Yunnan populations could successfully infest rice varieties ASD7 bearing bph2 and Rathu Heenati bearing Bph3, implying that these two populations had a higher adaptability to resistant rice varieties. The significantly negative relationship between female brachypterous rate and nymphal density in Zhejiang population showed a lower tolerance to high nymphal density of Zhejiang population than that of Guangxi and Yunnan populations. A higher resistance to high temperature and a lower tolerance to starvation were obviously found in Guangxi and Yunnan populations. The resistance to insecticide (Omethoate) of Zhejiang population was little higher than that of Guangxi population. It was suggested that the tolerance of different geographic populations of BPH to various adverse environmental stresses be closely related to their habitat characteristics. PMID- 11767536 TI - [Predation on Myzus persicae by Propylaea japonica adults with different extents of starvation]. AB - The study showed that the functional response of predation on M. persicae by the female and male adults of P. japonica with different extents of starvation belonged to the type of Holling II. Female adults had a larger attacking rate than male adults, but the predacious amount of M. persicae by female and male adult predators of different extent of starvation within 24 hrs had no significant difference. The predacious amount by female adult was larger than that of male. The significant difference of predacious amount between female and male adults increased with the time of their starvation and the prey density. The predation by unstarved female and male adult predators on M. persicae in 24 hours was concentrated at 6:00-18:00 and the predation rate (V) between female and male adults had no significant difference. The predation by starved female and male adults for 48 h on the prey in 24 hours was at 0-4 hours after the experiment started, and the predation rate(V) between female and male starved adults had no significant difference either. PMID- 11767537 TI - [Arthropod diversity in leafy vegetable field and sampling technology]. AB - Two sampling units (plant and quadrat) and two sampling methods (random and fixed) were adopted to compare the variation degree of the diversity of arthropod communities in different chinese cabbage fields. The results show that a lower variation degree was found when the random sampling method was adopted with quadrat (0.11 m2) as sampling unit at seedling stage and with plant as sampling unit from growing to mature stage. The community diversity was relatively steady, when the critical number of samples was more than 12 quatrats (0.11 m2) at seedling stage, 30 plants in growing period, and 20 plants at mature stage. The optimum sampling unit, sampling method and sampling number of arthropod diversity in leafy vegetable field were also determined. PMID- 11767538 TI - [Biological characteristics and occurrence regularity of Phassus excrescens Bulter]. AB - The biological characterisitics and occurrence regularity of Phassus excrescens were studied from 1997 to 2000 in the eastern part of Heilongjiang Province and Jilin Province. In this area, most of its individuals took two years to finish one generation, and over-wintered two times with eggs and larvae, respectively. At the end of June or the first ten days of July, larvae transferred to damage Fraxinus mandshurica. Feeding with artificial diet indoor, the larvae finished 6 instars before pupation. In artificial Manchurican ash forest, the larva mainly damaged the truck basal(below 20 cm) or truck of 2 to 20 years old Fraxinus mandshurica. The occurrence amount of this species was closely related to the forest age and the stand structure. Usually, pure artificial Fraxinus mandshurica stands and Fraxinus mandshurica-Pinus koraiensis mixed stands were damaged seriously, while Fraxinus mandshurica-Larix mixed forests were damaged lightly. PMID- 11767539 TI - [Morphological variation of spermatogenic cell nucleus in Macrobrachium nipponense(de Haan) and its status during reproductive evolution of Caridea]. AB - The morphological variation of nucleus during spermatogenesis in Macrobrachium nipponense and its status during the reproductive evolution of Caridean shrimp were investigated using transmission electron microscopy(TEM) technique. During the whole process of spermatogenesis, the nuclear morphology of spermatogenic cell varied from spherical or ellipsoidal to shallow-dish-like shape, and the nuclear membrane existed only in the rear part of mature sperm varied from intact to unintegrated one. The chromatin gradually varied from loosen to coacervative one, and then, developed differentially into two types of nucleus in the mature sperm, i.e., vesicular nucleus and filamental nucleus, which became an important characteristics of Macrobrachium nipponense. These nuclear morphological variations could be regarded as an important classifying property among Decapoda, on which, studies could contribute much to the analysis of the status of this species in the reproductive evolution of Caridean shrimp. PMID- 11767540 TI - [Medium selection and compounding of environmental eco-engineering through making use of life rubbish to produce carpet turf]. AB - Through making use of life rubbish as medium and choosing several materials with high feasibility as compound materials to produce carpet turf, the medium selection and compounding were carried out, and the growth effect of several kinds of turfgrass on each compound medium, its pH value and water stress function were also studied. Sawdust could raise the drought-resistant capacity of turfgrass by strengthening the water-retaining capacity of medium, and promote turfgrass growth. Plant ash showed a strong basicity, and when it made up 25% of medium, the pH value of the medium could be over 9. Fine river sand could improve the ventilating capacity of medium, but if mixed too much, it would decrease its nutritional level. It is suggested that the performance of compound mediums differed greatly with compound materials. Synthesizing each index studied showed that among all compounding mediums sawdust had a significantly positive effect, and had a broad application value. PMID- 11767542 TI - [Environmental fluorine level in Tibet]. AB - The concentration of fluorine in water, soil, fuel, food, vegetable and tea in Tibetan habitats with different environmental characteristic were measured by ion specific electrode potentiometer. The results showed that the fluorine concentration in water, soil, fuel, food vegetable, butter tea and Zanba both of them were made from brick teas was 0.06 mg.L-1, 0.45 mg.kg-1, 0.10 mg.kg-1, 0.06 0.33 mg.kg-1, 3.09 mg.L-1 and 3.61 mg.kg-1, respectively. The water-soluble fluorine content in brick tea which came from Sichuan and Yunnan Provinces reached up to 533.89-617.32 mg.kg-1. It is suggested that drinking brick tea may induce fluorosis in Tibetan habitats. PMID- 11767541 TI - [Phytotoxic effect of soil cadmium pollution on ramie]. AB - A microplot locating experiment was conducted to study the phytotoxic effect of adding Cd in soil on ramie plants. The results showed that the contents of chlorophyll a and b of leaf, and the photosynthesis productivity of ramie plant were significant reduced by the addition of Cd. As the content of soil Cd reached to 14 mg.kg-1, the biomass yield of the above-ground part of ramie plants was 20% lower than the control, and was 50% lower when soil Cd content was at 100 mg.kg 1. The number of effective tillers was a main factor affecting the yield of ramie raw fibers, and Cd addition had a relatively small effect on the quality of raime fibers. It is suggested that a synthetical technology of soil treatment and agronomic measures should be applied to eliminate the toxic effect of soil Cd and to enhance the resistance of plant against soil Cd pollution when employing ramie as the alternative of food and vegetable crops in a Cd-polluted region, which is also important for a higher yield of ramie. PMID- 11767543 TI - [A review on the eco-physiological study of poplars in oasis and its prospect]. AB - Poplar is the main component species in shelter forest subsystem, which forms a special kind of ecosystem in oasis with particular structure and function. Based on the studies on the ecophysiological characteristics of poplars in the Cele oasis, a preliminary comment was given on the experimental methods used at home and abroad, aim ed to facilitate the further studies on the characteristics of ecophysiology of poplars in the oasis. In order to sustain the oasis ecosystem management, the theoretical bases were also discussed on the optimization of shelter-forest structure and the selection of proper tree species. PMID- 11767544 TI - [Review on research of plant nutrient use efficiency]. AB - The concept of nutrient use efficiency is the central to the understanding of ecosystem function. We reviewed the concept of nutrient use efficiency and resorption, its expression and calculation, affecting factors and biochemical basis, we also analyzed the current problems in the studies of nutrient use efficiency, and pointed out the directions for future research work of this field. PMID- 11767545 TI - [Factors affecting transformation of Agrobacterium tumefaciens and their application on cereals]. AB - Agrobacterium tumefaciens mediated genetic transformation is the method most widely used in plant transformation. How to improve its transformation efficiency and extend its host range to include most cereals is what people concern about. There are many factors that influence the transformation efficiency, including the wounding response of plants, attachment of bacteria, induction of virulent gene, DNA repair and replication activity of plant cells, state of explant, etc. Recent research has proved that cerelas can be transformed effectively by A. tumefaciens under suitable conditions. This paper reviewed the recent progress in the two aspects. PMID- 11767546 TI - [Current situation of pollution eco-chemistry and its prospects]. AB - As a new discipline, pollution eco-chemistry comes into being with the development and intersection of ecology and environmental chemistry. Main contents of the subject were summarized: 1) movement and transformation of chemical pollutants and their microcosmically eco-chemical processes; 2) ecological effects, eco-toxicology and ecological risk assessment of chemical pollutants; 3) ecological chemistry of global changes; 4) analyses and monitoring of chemical pollutants in ecosystems; 5) eco-chemistry for pollution control. Under the guidance of knowledge innovation as its scientific goal, the research on pollution eco-chemistry will be devoted to a theoretical breakthrough. While doing a through basic research, we should pay attention to related applied research, in order to implement the technological and practical goal of the discipline. PMID- 11767547 TI - [Relationship between light and regeneration character of Huangshan pine]. AB - The growth and physiological characters of 1-3 years old Huangshan pine seedlings in pure and mixture plots with four different transparancy were determined, and the germination percentage of seeds and their complex stressing vigour were tested. Meanwhile, the regeneration mechanism of Huangshan pine in natural forest was studied in this paper. The results showed that the plumpness of seeds was 65%, the germination percentage was 27%, and the complex stressing vigour was 26%. The lower germination percentage affected the reproduction of Huangshan pine. The photosynthetic rate was more affected by solar energy, but less by humidity and surface temperature. With high light composation, Huangshan pine's regeneration under forest was difficult. The seedlings of Huangshan pine in mixed coniferous and broadleave tree plots were at a disadvantage because of slow growth and insufficient light. PMID- 11767548 TI - [Impacts of forest and precipitation on runoff and sediment in Tianshui watershed and GM models]. AB - This paper analyzed the impacts of foret stand volume and precipitation on annual erosion modulus, mean sediment, maximum sediment, mean runoff, maximum runoff, minimum runoff, mean water level, maximum water level and minimum water level in Tianshui watershed, and also analyzed the effect of the variation of forest stand volume on monthly mean runoff, minimum runoff and mean water level. The dynamic models of grey system GM(1, N) were constructed to simulate the changes of these hydrological elements. The dynamic GM models on the impact of stand volumes of different forest types(Chinese fir, masson pine and broad-leaved forests) with different age classes(young, middle-aged, mature and over-mature) and that of precipitation on the hydrological elements were also constructed, and their changes with time were analyzed. PMID- 11767549 TI - [Occurrence and control of frost in Tilia amurensis and Fraxinus mandshurica young plantations]. AB - The changes of minimum temperature periodical biological phenomena and frost in yound Tilia amurensis and Fraxinus mandshurica plantation stands were systematically analyzed based on the vertical gradient observation and plot investigation. Meanwhile, the resistance of Tilia amurensis to late frost was also studied. The results showed that the phenophase of T. amurensis was later than that of F. mandshurica. Influenced by significant temperature inversions in this area, the phenophase of T. amurensis and F. mandshurica changed regularly in different aspects and slope positions. The sprouts on west slope started earlier than that on east slope. The higher they grew on the slope, the earlier they sprouted, with the earliest sprout at the top of slope. Late frost in this area only took place when the trees were sprouting, but air temperature decreased significantly at the same time. The degree of injury from the late frost could be controlled effectively by selecting suitable site. Sites down the slope, especially the east slope, were not suitable for T. amurensis and F. mandshurica plantation in this research area. Chemical treatment and biological shading could prevent late frost injury through putting off sprout. Mixed plantations could prevent F. mandshurica and T. anurensis from late frost injury significantly, and the frost injury index and the proportion of the tree number of different injury grades were lower than those in pure stands. PMID- 11767550 TI - [Optimized models of logging-tending system in cutting areas]. AB - The comprehensive advantages of different logging-tending systems in Pinus massoniana forest cutting area were evaluated by set-pair analysis, based on the comparison of their economic and ecological benefits. The results showed that the optimized model for P. massoniana forests in Northern Fujian comprised 40% selective cutting, manual skidding, clear-cutting in ribbon, and natural regeneration with artificial aids, which could also be used in the nearby forests with conditions similar to the experimental area. PMID- 11767551 TI - [Ecosystem management of settlement area in Xingshan County]. AB - In the immigrant settlement area of Three-Gorges reservoir region in Xingshan County, Hubei Province, the ecological problems were the restoration of degraded ecosystem, rehabilitation of degraded crop land, and reconstruction of towns and villages. The key to the construction of the settlement area was reassigning the way of land use. The major aim of restoration of natural ecosystems should be to improve water conservation capacity of the land, because this area is located in the catchment of the Xiangxi River. The goals of management were determined as the coordinated development of both agricultural and natural forest ecosystems, the maintenance and increase of water conservation capacity of ecosystems, and the maintenance and extension of wildlife habitats. For the purpose of effective ecosystem management, the area was classified into four divisions of functional conservation region, functional rehabilitation, natural reserves and natural maintenance. The ecosystem management of the settlement area in Xingshan County was implemented in every land cell, using GIS and the typical grid-square survey method. The approach of multi-objects optimal spatial plan was developed in this paper, in which, special emphasis was put on the ecological, economic and social benefits in the construction of towns and villages. According to the scheme of management, the cover of forest in the settlement area, would increase by 30.19%, and water conservation capacity of the ecosystems would raise by 38.7%. PMID- 11767552 TI - [Systematic analysis of agro-ecoclimatic resources in Gansu Province]. AB - Based on the over years data from 86 meterological stations in Gansu Province, the agro-ecoclimatic resources in this province was systematically analyzed. Resource indices Cr, efficiency indices Ce and utilization coefficient K were calculated by using the dynamic models of agro-ecoclimatic suitability degree. According to the average monthly efficiency indices Ce, the agro-ecoclimatic resources were divided into 7 types and 3 subtypes by fuzzy cluster. The potentiality matching condition and utility degree of agro-ecoclimatic resources showed the evident characteristic of spatial differentiation. Generally, the south was superior to the north, and the east was superior to the west in terms of these parameters, with the type of South Gansu Mountain much better than that of Hexi Corridor. Some suggestions about the exploitation and utilization of the agro-ecoclimatic resources in Gansu province were proposed. PMID- 11767553 TI - [Cluster analysis methods appropriate for classification of drought-resistant wheat ecotypes]. AB - The appropriate cluster analysis methods for classification of drought-resistant wheat ecotypes were investigated, based on the analysis of 21 morphologic and agronomic characters of 15 winter wheat cultivars. According to the proximity degree to the results from experts experiences, the cluster results using original data were orderly better than those using Varimax orthogonal rotation, Promax skew intersection rotation, and principal component analysis with phenotypic mean's correlation matrix. The results using Euclidean distance were greater than those using Mahalanobis distance. The clustering methods of correspondent analysis and fuzzy cluster were better than those of nearest distance, furthest distance or group average method (UPGMA). Among all cluster results from various methods combined, the two cluster results from the fuzzy cluster using original data and from the correspondence analysis method were closest to the results of experts' experience. Based on both comparisons of results and examination of the performance of different strategies with several statistical properties, the two methods mentioned above were also acceptable. PMID- 11767554 TI - [A wintering habitat model for red crown crane]. AB - A mathematical model was established based on GIS and RS to simulate and predict the habitat distribution of red crown crane(Grus japonensis) in Yancheng Biosphere Reserve, Jiangsu Province, China. The model was tested through calculating the match coefficience of observed and predicted presence/absence data, which was 72.63%, showing that the model could be used to reflect the habitat distribution of red crown crane. PMID- 11767555 TI - [A method for designing buffer zone in Yancheng Biosphere Reserve: taking red crown crane as objective species]. AB - Social, economic, ecological and geomorphic factors are needed to be considered when designing the buffer zone of natural reserve. In this paper, the Analytic Hierarchy Process(AHP) was applied to design the width of buffer zone. Under considerating the influences in different sections around the reserve, different widths of the buffer zone were designed, and a case study was carried out in Yancheng Biosphere Reserve. The results showed that the proposed method was reasonable and practicable in designing the buffer zone of nature reserve. PMID- 11767556 TI - [Impact of starvation on predation by male adult Chrysopa septempunctata]. AB - The predation on Schizaphis graminum by male adult Chrysopa septempunctatata at various levels of starvation was examined in this paper. Th results showed that the functional reactive types of predator were not altered by its starvation duration, and the amount(Na) of catched S. graminum by C. septempunctata within 24 hrs varied with duration time(t), which could be expressed by the model: Na = 100/(1 + e-0.3088 - 0.0996t). The relationship between predation rate(v) and time(x) could be described as v = 6.7117 x-0.7928. The male adult predators preferred feeding on the young preys. PMID- 11767557 TI - [Impact of high temperature on testicular growth and development of valuable silkworm Antheraea yamamai(Lepidoptera: Saturiidae)]. AB - The results indicated that high temperature had a significant impact on the growth and development of testis in Japanese oak silkworm Antheraea yamamai. The testicular size of the 3rd and 4th instar larvae increased within the range from 20 to 29 degrees C, and slightly decreased at 32 degrees C. While in the 5th instar, it decreased within the range from 20 to 26 degrees C, with the biggest size at 20 degrees C. The testis was almost hard to grow and develop because the larvae could not survive at 29 to 32 degrees C. When the mature larvae were treated at 32 degrees C at the beginning of coconing or at the 1st or 6th day of pupating, the growth of testicular size and spermatogenesis were significantly arrested, and the sperm number and the content of soluble protein in the testis markedly decreased. When the male moth of the 1st day was treated at 32 degrees C, the activity of the sperms in the testis obviously decreased, in contrast to the treatment at 20 degrees C. It is concluded that for the egg raising of the silkworm, its mature larvae, puape in cocoons and male moths should not be exposed to 32 degrees C from cocooning to adult stage. The proper temperature for rearing 3rd, 4th and 5th instar larvae was discussed. PMID- 11767558 TI - [Lifetable of cotton bollworm under different control condition]. AB - The lifetables of 3rd and 4th generation of cotton bollworm Helicoverpa armigera Hubner were established by action factors under four different control conditions. The results showed that under natural control, the egg parasitic rates of 3rd and 4th cotton bollworm were 4.39% and 1.19%, the predatory rates were 21.11% and 15.80%, and the larvae parasitic rates were 19.34% and 16.20% respectively. The indexes of population trend were only 0.0032 and 0.0014 respectively, after using selective pesticides IKI and Bt to control cotton bollworm. Though the index of population trend decreased to 48.66% and 61.67% after contantly praying chemical pesticides, the number of predators also decreased to 23.48% and 41.26% respectively. Transgenic Bt cotton could inhibit the population increase of cotton bollworm, but had no effect on predators. The parasitic rates of 3rd and 4th cotton bollworm on Transgenic Bt cotton were 51.14% and 0% respectively, as compared to control. PMID- 11767559 TI - [Effect of rice variety resistance on population dynamics of Nilaparvata lugens and Sogatella furcifera]. AB - The effect of rice varieties with different insect-resistance on dynamics of Nilaparvata lugens and Sogatella furcifera population was examined, based on the investigation of their inhabiting ratio, egg amount, survival rate of egg and nymph, nymph development, and the amount of their offspring population. Four rice varieties, TN1, N22, AsD7 and Ptb33 were investigated. Ptb33 had a significantly lower inhabiting ratio, egg amount, and survival ratio of eggs and nymphs of both parasitic populations, a prolonged development time from nymphs to adults, and an inhibited offspring population, indicating an evident resistance of this host variety. N22 and AsD7 inhibited the development of offspring S. furcifera and N. lugens, respectively. The parasitic populations of S. furcifera and N. lugens developed more rapidly on TN1, compared with N. lugens population on N22 and S. furcifera on AsD7. The relationship between the quantitative dynamics of both population and rice variety replacement was discussed, and the possibility of using resistant rice varieties to control these two insect populations was also analyzed. PMID- 11767560 TI - [Population growth, distribution pattern and sampling technique of Thrips palmi on eggplant]. AB - Population growth of Thrips palmi Karny on eggplant (Solanum melongena L.) were analyzed by mathematical models. The rate of population increase (r) of the adults and immature (instars 1-2) T. palmi were estimated to be 0.0630 and 0.0801 respectively in the open fields, and 0.0983 and 0.1036 respectively in the greenhouse. K value of logistic curve of T. palmi was estimated to be 33.90 in the greenhouse, and 23.50 in the open fields. The relationship between mean crowding (M*) and mean density (M) of T. palmi per eggplant leaf were estimated by Iwao's M*-M regression. The regression equation of adult and immature T. palmi on eggplant were: M* = 0.6011 + 1.468M and M* = 7.2515 + 2.064M respectively. The regression equation of the number of adult and immature was M* = 7.5138 + 1.9119M. When the population density of the adults and immature T. palmi per eggplant leaf were 10 to 100, the number of sampling should be 78 to 44. PMID- 11767561 TI - [Effects of temperature, relative humidity and pH on germination of chalkbrood fungus, Ascosphaera apis spore]. AB - Studies on the effects of environmental temperature, relative humidity and pH value on the germination of Ascosphaera apis spore at the stages of activation, enlargement and germ-tube production showed that the germination was found to be independent of temperature within the range of 15-40 degrees C was and 25-40 degrees C, respectively at the stage of activation and enlargement, but closely correlated with the temperature within the range of 25-37 degrees C at the stage of germ-tube production, with the optimum range of 31-35 degrees C. Relative humidity below 80% inhibited spore germination. pH value within the range of 5 7.8 did not affect the spore germination significantly, but pH < 5 reduced the enlargement and germ-tube production drastically. The results indicated that A. apis is a highly specialized pathogen for the life in honeybee larvae. PMID- 11767562 TI - [Dynamics of respiration pathway in transgenic salt-tolerant wheat and its receptor under salt stress]. AB - Using transgenic salt-tolerant wheat 89122 and its receptor Longchun 13 as test material, the dynamic changes of respiration pathway of wheat seedlings at different salt concentration were studied. The appearance of salt respiration was later in 89122 than in Longchun 13. The changes of Valt and rho Valt of both varieties had different patterns during salt stress process. Valt was suppressed by high salt levels, but could be induced by low salt levels in Longchun 13. The rho Valt and rho' Vcyt of two varieties were cooperatively regulated with each other to adapt to salt stress, and rho' Vcyt was the main electron transport pathway. The possible physiological roles of cyanide-resistant respiration were also discussed. It was suggested that the operation intensity of cyanide resistant respiration could serve as a physiological index of plant salt tolerance. PMID- 11767563 TI - [Effect of osmotic stress on wheat membrane injury under different CO2 concentrations]. AB - This paper studied the variation of active oxygen content and membrane permeability in leaves of spring wheat seedling exposed to osmotic stress under normal 350 microliters.L-1 and doubled CO2 concentration 700 microliters.L-1. The results indicate that the increasing rate of O2.- and H2O2, and the membrane permeability in wheat leaves exposed to osmotic stress in normal CO2 concentration were higher than those in doubled CO2. Accordingly, it is suggested that doubled CO2 can reduce the membrane oxidative injury caused by osmotic stress, and increase plant drought resistance. PMID- 11767564 TI - [Effect of elevated CO2 concentration on photosynthesis and antioxidative enzyme activities of wheat plant grown under drought condition]. AB - The photosynthesis and antioxidative enzyme activities of wheat plants grown in two open-top chambers with CO2 concentrations of 350 mumol.mol-1 and 700 mumol.mol-1 were examined under drought stress. The result showed that elevated CO2 concentration obviously enhanced the photosynthesis, stomatal resistance and water use efficiency, but decreased the transpiration of wheat. Doubled CO2 concentration significantly increased the activities of CAT, POD and SOD, which enhanced the abilities of antioxidative defence and drought tolerance. PMID- 11767565 TI - [Dynamic changes of respiration pathway and active oxygen levels in subcultured tobacco callus]. AB - During the growth and senescence of tobacco callus, the total respiration rate showed two peaks on the 11th and 19th day, respectively. The development and operation of alternative pathway increased gradually, reached the maximum between two respiration peaks, and then declined in the following days, but the cytochrome pathway was still as a main electron transport pathway consistently. Analysis on the levels of active oxygen species during the growth and senescence process in tobacco callus suggested that H2O2 and O2.- were involved in some way in the induction of the development and operation of the alternative pathway, but the increase of production rate of OH might suppress both the development and operation of the alternative pathway, which were enhanced by H2O2 and O2.- respectively. These results were further proved by the use of active oxygen scavengers. The possible participation of the alternative pathway enhanced by active oxygen in the initial senescence process was discussed. PMID- 11767566 TI - [Effects of Ca2+, ABA and H3PO4 on relaxing stress of Na2CO3 and NaCl]. AB - Two groups of Aneurolepidium chinense seedlings were stressed by 300 mmol.L-1 NaCl and 100 mmol.L-1 Na2CO3, respectively and the effect of ABA, Ca2+ and H3PO4 on relaxing their stress was studied. The results show that external Ca2+, ABA and H3PO4 could obviously mitigat the inhibitory effect of NaCl and NaCO3 on seedling growth. In the treatment of Na2CO3, praying it on leaves had a better effect than root-irrigating, while in the treatment of NaCl, there was no significant difference. The effect of Ca(NO3)2 was much better than that of CaCl2, and of mingling CaCl2 and ABA had a much better effect than CaCl2 or ABA alone. PMID- 11767567 TI - [Nitrogen dynamics in different organs of Calamagrostis angustifolia and Carex lasiocarpa in Sanjiang plain]. AB - The dynamics of nitrogen content and storage in different organs of Calamagrostis angustifolia and Carex lasiocarpa which are dominant vegetation in swamp wetland were determined, and the utilization rate of nitrogen and its nutrient limitation in the region were analyzed. The results showed that the aboveground and underground biomass might be described by p = gamma + alpha t + beta t2 and p = a0 + b0t, respectively. The content of total N, NH4(+)-N and NO3(-)-N varied widely with different organs because of the effects of soil water, nutrient content, atmospheric temperature, vegetable feature and selective absorption to nitrogen, etc. The content of NO3(-)-N in different organs varied less than that of NH4(+)-N, and NH4(+)-N/NO3(-)-N was < 1. The N:P content less than 14 in two vegetations showed that it was N but not P was the limitation nutrient to the growth of vegetation in this region, moreover, the limitation was less in July than in August. This conclusion was also drawn from the analysis of the NH4(+)-N and NO3(-)-N content in soil. PMID- 11767568 TI - [Nitrogen content variation in litters of Deyeuxia angustifolia and Carex lasiocarpa in Sanjing plain]. AB - This paper dealt with the litter of two dominant species Deyeuxia angustifolia and Carex lasiocarpa in swamp of Sanjiang Plain, and analyzed the seasonal variation and content feature of nitrogen in litter and its roles on maintaining matter equilibrium in ecosystems. The nitrogen content in litter decreased with the increasing temperature and above-ground biomass. The weightlessness rate of litter increased with time, and the annual accumulative weightlessness rates of D. angustifolia and C. lasiocarpa were 32.2% and 27.7%, respectively. The annual accumulative nitrogen input amount of D. angustifolia community was 1478 mg.m-2, C. lasiocarpa 587 mg.m-2, while the annual accumulative nitrogen output amount in litter of D. angustifolia community was 759 mg.m-2, C. lasiocarpa 410 mg.m-2. It was suggested that the nitrogen input amount was higher than output, and that the state of nitrogen accumulation was beneficial to the stability of the ecosystems. PMID- 11767569 TI - [Element concentrations in Rheum palmatum and R. likiangense plants and soil in Tibet plateau]. AB - The characteristics of element concentrations in Rheum palmatum and R. likiangense plants and soil were studied using ICP method. The results showed that the P concentrations in soil was significantly lower than that in leaves and rhizomes; Fe concentration was 50-100 times higher in soil than in rhizomes, and leaves, and without significant difference between rhizomes and leaves; Na, Mn and Cu concentrations appeared soil > leaves > rhizomes; and Ca concentration showed soil < leaves < rhizomes for R. palmatum, and soil > leaves > rhizomes for R. likiangense. Although K, Mg, Ca, Mn and Zn concentrations were obviously different between soils of the 2 species, K and Mg concentrations were consistent in their leaves or rhizomes, and the difference of Ca, Mn and Zn concentrations between their rhizomes was insignificant. PMID- 11767570 TI - [Ecological study on relationship between desertification process and vegetation dynamics in west of northeast China: vegetation classification]. AB - Based on the data obtained from 72 plant community plots and 276 plant species in Hulunbeier Sandy Land and Kerqin Sandy Land in the northeast desertification region of China, TWINSPAN analysis was carried out. Meanwhile the practical classification result was obtained by Detrended correspondence Analysis (DCA). Under the vegetation classification principles of China, the vegetation classification system of the desertification regions in northeast China was preliminarily established, which includes 6 vegetation types, 11 subtypes, 40 formations, and 55 associations. PMID- 11767571 TI - [Comparison analysis between potential and actual pattern of artificial oases in arid region]. AB - Based on theoretical analysis and demonstration research, the conception of potential pattern in the agriculture landscape of artificial oases in Xinjiang arid region and its analysis unit were discussed. The potential landscape pattern was defined as the one composed by spatial units with basic characteristics and properties which had no change or less change with the time. In agriculture landscape, soil was found to be a relatively stable element, and hence, different soil classification unit could be used to analyze the potential landscape pattern. A case study was carried out to analyze the potential and actual pattern of the artificial cases in Shihezi reclamation area by using the indexes of diversity, evenness, aggregation, mean patch elongation, patch shape fragmentation and mean patch fractal dimension. The result showed that the landscape pattern changed orderly from the potential to actual pattern, and the potential pattern could be used as the absolute criterion for researches on pattern changes in agriculture landscape. PMID- 11767572 TI - [Optimal models on sustainable management of oases ecosystem in southern margin of Taklamakan Desert]. AB - On the basis of analyzing the distribution feature of water resource and the canal water utilization coefficient of oases in southern margin of Taklamakan Desert, observing the wind prevention efficiency of shelterbelt through a simulation experiment in wind tunnel, and 15 years researching the comprehensive control of desertified land in Cele Oasis, a series of optimal models on sustainable management of oases ecosystem is southern margin of Taklamakan Desert were proposed i.e., the optimal model on "moderated osais", the optimal model on structure of wind-breaks, the optimal model on comprehensive control of desertified land, and the optimal model on planting structure of corps. PMID- 11767573 TI - [Impact of precipitation and underground water level in the edge of oases on growth and decline of Nitraria tangugtorum community]. AB - Based on the data from underground water monitoring, meterological measuring and fixed sample square investigating in successive years at the edge of the oasis in Minqin, Gansu, the impact of precipitation and underground water on the growth and decline of Nitraria tangutorum community was studied. The result showed that the desiccated environment in oases driven by the decline of underground water level was favorable for the growth and develoment of N. tangutorum community, and made this species more xerophilous. This declining underground water level was not a limiting factor for N. tangutorum growth in late years. These N. tangutorum dominated communities were predicted to survive comparatively longer, and to function as sand fixer and wind breaker at oasis edge in Minqin. When average annual precipitation was about 110 mm, N. tangutorum would maintain its normal growth, but the community couldn't spread freely. Only when the annual precipitation was up 140 mm in two years running, could its growth be improved. PMID- 11767574 TI - [Design and implementation of a landscape analysis system based on remote sensing data]. AB - Because of the functions of Geographic Information System(GIS) being not satisfied to the requirements of landscape analysis, a landscape analysis system was designed with Visual C++ and demonstrated with remote sensing data. This system adopted the method f picking-up patch boundary pixel set, improved the patch searching speed, and supplied some landscape analysis functions, such as the calculation of the distance between patches, and the boundary length of neighboring patch, which are not provided by current GIS. It was used to analyzed the landscape of suburbs in northwest Beijing, and the shortcomings of current GIS applied in landscape analysis were overcome. PMID- 11767575 TI - [Effect of cadmium on soil animal community structure]. AB - A indoor simulating test showed that there existed a close relationship between the community structure of soil animal and the concentration of soil Cd. When the concentration of soil Cd was high (99.48 mg.kg-1), the species, quantity, diversity index, homogeneous index, and abundance of soil animal were low. With the concentration going down, all indexes above increased gradually. When the concentration of soil Cd was 2.27 mg.kg-1, all the indexes were the same as control. The species and individuals of soil animal were negatively related with the natural logarithm of Cd concentration in soil. PMID- 11767576 TI - [Correlation of photoplankton and its environmental factors in Rushan Bay]. AB - The relationship between photoplankton and its environmental factors in Rushan Bay was studied from June to September, 1995. The result shows that there existed a negative correlation between the number of photoplankton and the content of inorganic nutrients. The correlation coefficients for inorganic nitrogen and phosphorus were -0.67 and -0.80, respectively. The dissolved oxygen and chlorophyll-a were positively correlated to photoplankton, and their correlation coefficients were 0.92 and 0.85 respectively. Based on N/P analysis, the content of inorganic nitrogen was relatively short to the reproductive growth of photoplankton during experimental months, except for the last ten days of August. PMID- 11767577 TI - [Environmental characteristic of walleye pollock fishing ground in high seas of the Okhotsk Sea in summer]. AB - Based on the acoustic survey on the resource of walleye pollock (Theragra chalcogramma) in the high seas of the Okhotsk Sea, the distribution of walleye pollock and the environmental characteristics of its fishing ground were studied, and the relationship between them were analyzed. In August, the high schooling area of walleye pollock was situated in the waters with a depth of less than 500 meters and to the north of 55 degrees N. Walleye pollock mainly distributed in 150-300 m depth, and lived in groups. The main food was Euphausia pacifica, and the densely populated area of wall-eye pollock was roughly consistent with that of Euphausia pacifica. The thermocline was observed at 0-50 m depth, the temperature changed at a rate of 0.25 degree C per meter, and the cold water mass was roughly located in 50-150 m layer. The fish was mainly distributed in the layer below the cold water mass, because of the impeding effect of thermocline and the limiting action of fish food. It seldom inhabited the water below 400 m depth, partly because the dissolved oxygen there was rather low. PMID- 11767578 TI - [Advance in studies on compensatory growth of aquatic animals after starvation or undernutrition]. AB - This paper reviewed the studies on the compensatory growth of aquatic animals after starvation or undernourisment. The extent of compensatory growth, its affecting factors, physiological mechanisms, changes in chemical composition and dynamics of growth rate were discussed. The experimental design problems and the application prospects of related studied were also analyzed. PMID- 11767579 TI - [Protein secretion from drug-resistant bacteria--a suitable target for new antibiotics]. AB - This paper reviewed the pathways of bacterial protein secretion and discussed the targets of pathogenic bacteria for antibiotics. Inhibition of protein secretion could lead to the growth decline, morphological alteration, and reduction of bacterial virulence, as well as the deprivation of their drug resistant. It was concluded that protein secretion could be a suitable target for new antibiotic agents. PMID- 11767580 TI - [Factors affecting colonization of introduced microorganisms on plant roots]. AB - Microorganisms such as biological control agents (BCA), plant growth-promoting rhizobacteria (PGPR) and yield increasing bacteria (YIB) were introduced along growing roots. The colonization process of introduced bacteria was proved that they attached root tipfirst, then distributed along roots, multiplicated there, and survived as certain population size. The colonization location was closely related with root exudates, which was usually at the junction between cortex cells or at the base of lateral roots or root hairs. The variation of colonization by introduced microorganisms in the rhizosphere was caused by biotic and abiotic factors. Biotic factors included the physiological characters of introduced microorganisms and interactions between introduced microorganisms and native microbes. The more important factors were plant genotypes which associated with introduced beneficial microbes and regulated the population and community of those microbes affecting the colonization of introduced microorganisms. Abiotic factors here referred to soil environmental conditions, e.g., soil texture, water content, soil temperature and pH value. PMID- 11767581 TI - [Ecotourism exploitation model in Bita Lake Natural Reserve of Yunnan]. AB - Bita lake provincial natural reserve is located in Shangri-La region of North western Yunnan, and was set as a demonstrating area for ecotourism exploitation in 1998. After a year's exploitation construction and half a year's operation as a branch of the 99' Kunming International Horticulture Exposition to accept tourists, it was proved that the ecotourism demonstrating area attained four integrated functions of ecotourism, i.e., tourism, protection, poverty clearing and environment education. Five exploitation and management models including function zoned exploitation model, featured tourism communication model signs system designing model, local Tibetan family reception model and environmental monitoring model, were also successful, which were demonstrated and spreaded to the whole province. Bita lake provincial natural reserve could be a good sample for the ecotourism exploitation natural reserves of the whole country. PMID- 11767582 TI - [Effect of combined treatment of 60Co gamma-ray and EMS on antioxidase activity and ODAP content in Lathyrus sativus]. AB - Lathyrus sativus seeds were treated with 60Co gamma-ray and EMS(ethyl methane sulfonate), and their emergence rate and SOD, POD and CAT activities were determined. The result indicated that the treatment decreased the emergence rate. The activities of SOD and POD were changed in accordance with the increase of irradiation dose and EMS concentration, while that of CAT had no obvious change. After treatment, the ODAP content in Lathyrus sativus decreased. Amutant was developed, with toxin content of 0.1%, compared to 0.2% in control. PMID- 11767583 TI - [Effect of Nerium indicum on killing Oncomelania hupensis]. AB - A laboratory experiment at 20 +/- 5 degrees C shows that the water extract of fresh Nerium indicum had an obvious effect on killing Oncomelania hupensis. Treated with 0.1% water extract for four days, the mortality of O. hupensis was up to 100%. The effect of different tissues of N. indicum on O. hupensis was in order of stem phloem > leaf > root phloem > flower. The effect of N. indicum on O. hupensis was about ten times higher than that of Pterocarya stenoptera and Rumex japonicus, and was equal to that of 1 x 10(-3) mg.L-1 niclosamidum. PMID- 11767584 TI - [Nutrient retranslocation in fine roots of Cunninghamia lanceolata, Alnus cremastogyne and Kalopanax septemlobum in the mixed plantations--a pilot study]. AB - Comparison of N, P and K concentrations in live and dead fine roots of Cunninghamia lanceolata, Alnus cremastogyne and Kalopanax septemlobum showed that the fine roots of A. cremastogyne had a stronger ability of N retranslocation than K. septemlobum's, but no N translocation occurred in C. lanceolata's. P retranslocation could be found in the fine roots of the all test tree species except C. lanceolata. As for K, it could translocate from fine roots to tree bodies of all these tree species before senescence. Based on the analysis on the difference of N, P, and K concentrations in live fine roots of each pair of tree species in the mixtures, it was suggested that N and K could respectively transfer from the root system of A. cremastogyne and K. septemlobum to the fine roots of C. lanceolata, and the mechanism could be clarified through exploring the ecological process of root-soil interface. PMID- 11767585 TI - [Community characteristics of rare trees at Dalaoling of Three-Gorge reservoir area in western Hubei Province]. AB - The quantitative characteristics, plant frequency in layers and species diversity of David involucrata var. vilnoriniara, Euptlea pleiosperma, Stewartia sinensis and Pterostyrax psilophtila communities at Dalaoling National Forest Park Reserve of Yichang were studied qualitatively and quantitatively. The community composition and structure were made clear, the succession courses and stages of the communities were revealed, and the role of these rare trees on the succession course of communities and the cause of being in imminent danger were analyzed, which provided a theoretical basis for protecting the rare trees in the Three Gorge reservoir area. PMID- 11767586 TI - [Distribution pattern and its dynamics of Taxus chinensis var. mairei population on Yunbaoshan Mountain]. AB - Field data were sampled by the method of contiguous grid quadrate, and t-test of v/m ratio, negative binomial parameter, Green's index, Cassie's index, dispersion index, clumping index, mean crowding index and patchiness index were used to analyse the distribution pattern and its dynamics of Taxus chinensis var. mairei population. The result shows that the distribution pattern was clustering. From sapling to grown-up tree, the clustering degree was decreasing, while the big trees had a random distribution. PMID- 11767587 TI - [Quantitative characteristics of rare and endangered Castanopsis kawakamii population]. AB - In this paper, a new self-adaptive model for population growth, i.e. S = exp(alpha ln2(1 + ce-rt) + beta ln(1 + ce-rt) + gamma) was established, which combined Logistic, Smith, Gompertz, Gui-Lawson, Zhang-Logistic and Liu-Logistic models. Estimations with genetic algorithm showed that the new model was more suitable than other models to simulate the actual growth trend of Castanopsis kawakamii population. PMID- 11767588 TI - [Impact of salinity on accumulation of several metal elements in Bruguiera gymnorrhiza seedlings and Ca effect]. AB - The contents of K, Ca, Na and Mg in different organs of Bruguiera gymnorrhiza seedlings cultured in sand bases with solutions of 400 mmol.L-1 NaCl and different concentrations of CaCl2 were determined. In the treatment of 400 mmol.L 1 NaCl, Na was largely accumulated in organs, which caused the decrease of K/Na and Ca/Na, and decreased dry matter accumulation in seedlings. Supplemental CaCl2 decreased the accumulation of Na in seedlings, increased the rations of K/Na and Ca/Na and the accumulation of dry matter, and thereby, mitigated salt stress. The suitable concentration of CaCl2 was 10-15 mmol.L-1. It was concluded that B. gymnorrhiza seedlings cultured at high salinity accumulated more metal ions, which enhanced osmotic adjustment of plants, and kept highly selective absorption of K/Na. These characteristics are the main physiological mechanisms of the adaptation of B. gymnorrhiza to high salinity in estuary and coast, while suitable Ca/Na in soil is one of the important causes that B. gymnorrhiza can survive and regenerate in high salinity coast. PMID- 11767589 TI - [Caloric values and ash contents of some mangrove woods]. AB - The caloric values and ash contents of some mangrove woods in Dongzhai Harbor Mangrove Forest Reserve of Hainan Province were determined in Summer, and the changes of the caloric value of Kandelia candel woods at different latitudes were studied. The ash content of mangrove woods was low, ranging from 2.43% to 5.17%; and their gross and ash-free caloric values ranged from 17.23 kJ.g-1 to 19.21 kJ.g-1 and from 17.70 kJ.g-1 to 20.10 kJ.g-1, respectively. Sonneratia apetala wood had the lowest gross and ash-free caloric values. The caloric value of Kandelia candel wood decreased with increasing latitude in Summer. PMID- 11767590 TI - [Distribution patterns of shoots, flowers and seeds in Ginkgo biloba canopy and their relationships]. AB - The distribution patterns of shoots, flowers and seeds in the canopy of 14 years old engrafted Ginkgo biloba and their relationships were investigated with stratification method. The result shows that long shoots, short shoots, bearing shoots and flowers uniformly distributed in the central section of canopy. From the top to the bottom, the average age and the divaricating angle of long shoots increase 51.3% of the seeds distributed in 180-320 cm layer from the ground. The number of shoots, flowers and seeds in different canopy layers was closely correlated. PMID- 11767591 TI - [Dynamics of phenolics content of Chinese fir stump-roots and the rhizosphere soil and it's allelopathy]. AB - Studies on the releasing pattern of phenolics during the decomposition of Chinese fir stump-root and on its allelopathy show that the phenolics contents in stump roots decreased with their decomposition. Roots had a higher content of phenolics than heart stumps, and edge stumps had the least. The phenolics was released during decomposition, and accumulated in the soils around stump-roots. Pot culture experiment showed that phenolics affected the germination of Chinese fir seeds. The correlation analysis between the density of Chinese fir stump-root and the tree height and base diameter (BD) of its saplings proved that Chinese fir stump-roots had a negative impact on the growth of the next generation of Chinese fir plantations. It is suggested that the traditional operation of Chinese fir plantations should be reformed, and the stump-roots should be cleared from woodland before reforestation. PMID- 11767592 TI - [Energy distribution of Phyllostachys pubescens ecosytem in north Fujian]. AB - Based on the data obtrained from 40 Phyllostachys pubescens plots in Jianou City of Fujian Province, the distribution of energy was studied in this paper. The results showed that the energy contained in stems, branches and leaves, and underground parts of P. pubescens ecosystem were 4.2322 x 10(8) kJ.hm-2, 0.9230 x 10(8) kJ.hm-2 and 1.7643 x 10(8) kJ.hm-2, accounting for 61.32%, 13.11% and 25.57% of the total energy respectively. PMID- 11767593 TI - [Utilizable value of wild economic plant resource--acron kernel]. AB - Peking whites breeding hens were selected. Using true metabolizable energy method (TME) to evaluate the available nutritive value of acorn kernel, while maize and rice were used as control. The results showed that the contents of gross energy (GE), apparent metabolizable energy (AME), true metabolizable energy (TME) and crude protein (CP) in the acorn kernel were 16.53 mg/kg-1, 11.13 mg.kg-1, 11.66 mg.kg-1 and 10.63%, respectively. The apparent availability and true availability of crude protein were 45.55% and 49.83%. The gross content of 17 amino acids, essential amino acids and semiessential amino acids were 9.23% and 4.84%. The true availability of amino acid and the content of true available amino acid were 60.85% and 6.09%. The contents of tannin and hydrocyanic acid were 4.55% and 0.98% in acorn kernel. The available nutritive value of acorn kernel is similar to maize or slightly lower, but slightly higher than that of rice. Acorn kernel is a wild economic plant resource to exploit and utilize but it contains higher tannin and hydrocyanic acid. PMID- 11767594 TI - [Effect of nitrogen on water use efficiency of apple tree]. AB - This paper studied the effect of nitrogen fertilizer on water use efficiency(WUE) and relevant parameters of two years old potted apple trees(Starkrimson/Malus hupenensis) under different soil moisture condition. The results showed that under adequate soil moisture, WUE was decreased with increasing application of nitrogen fertilizer. Nitrogen fertilizer application resulted in an increase of stomatal conductane. Consequently, the transpiration rate was increased more than photosynthetic rate did. Under soil drought, the WUE of plants applied with nitrogen fertilizer was apparently higher than that of control. The WUE value was in the order of high N > medium N > low N. The improvement of WUE was due to the increase of mesophyll capacity, which led to the promotion of photosynthesis. PMID- 11767595 TI - [Wind tunnel experiment on canopy structural parameters of isolated tree and wind velocity field characters nearby]. AB - The canopy structural parameters(porosity beta and permeability alpha) of isolated tree, and the wind velocity field character nearby were analyzed by wind tunnel experiment. The results show that alpha and beta fitted the function of alpha = beta 0.6, and the wind velocity nearby decreased in ellipsoid contour. The contour increased with increasing tree height and canopy width, and decreased with increasing permeability (or porosity). The isotach became the shape of ellipses or elliptic segments in horizontal and vertical plans. PMID- 11767596 TI - [Horizontal thermal characteristics at forest edge in calm tropical region of China]. AB - The temperature measurement at southwest-facing edge of a rubber forest was conducted in a calm tropical region of Xishuangbanna, Yunnan, China in January 1998, and the daytime thermal characteristics and their time-space variations nearby the edge of the rubber forest were discussed. There was an obviously thermal effect at forest edge. The depth of edge influence on soil surface temperature was up to 13 m from the edge into the forest. Soil surface temperature reached its highest at 4.5 m outside the forest. The highest air temperature occurred at 0 m of the edge. The heat transfer nearby the edge was quite different in number and in direction. Outside the forest, the heat was transferred from ground to air on almost daytime, while at interior of forest, was opposite after the noon. The heat was transferred from the rubber canopy to the ground. At the forest edge, such variation was complex, depended mainly on location and time. PMID- 11767597 TI - [Effect of unsymmetrical cutting along both river slopes on rainstorm-runoff process]. AB - A simulation experiment was conducted to compare the effect of cutting and no cutting at both slopes along a river on the rainstorm run-off in catchment, and a model was constructed. The results showed that the appearance of outflow and peak flow of surface run-off was later on forest slope than on forest-cutting slope. On forest slope, the duration was prolonged, and the peak flow and surface runoff were lower. These effects were more obvious as the slope gradient was bigger. When rain intensity was 1.98 mm.min-1 and rainfall was 108.8 mm, the peak flow and the total runoff on both forested slopes of gradient 15 degrees was 5% and 4% less than that on the cutting slopes, respectively. PMID- 11767598 TI - [Effect of land management in winter crop season on seasonal variations of CH4 emissions from rice paddy soils]. AB - A pot experiment in greenhouse was carried out to study seasonal variations of CH4 fluxes from rice paddy soils and the effect of land management in winter crop season on the seasonal variations. The results showed that four emission peaks occurred respectively 13 days after flooding and 7, 40, 91 days after rice transplanting, and CH4 emission amounts during the first 30 days after flooding accounted for as high as 67.5%, 35.5% and 33.3% of the total emission amounts during the observing period of 133 days for treatments with dry fallow but rice straw being applied just before flooding, alfalfa, and flooded fallow in winter crop season. However, for treatments with dry fallow but rice straw being applied before winter crop cultivating and winter wheat in winter crop season, CH4 emission amounts during the first 50 days after flooding just accounted for 0.27% and 6.74 of the total emission amounts during the observing period, and CH4 fluxes thereafter were also very small. Difference in the seasonal variation patterns of soil Eh due to land management in winter crop season was the main reason why seasonal variation patterns of CH4 fluxes from different treatments were different. PMID- 11767599 TI - [Yield increasing and water saving effect under different soil fertility improvements in wheat-corn intercropping field in Huabei Plain]. AB - Water resource in agriculture in Huabei Plain has been increasingly reduced in recent years. In order to reduce water evaporation and improve water utilization efficiency, the field experiment on water saving under different soil fertility improvements was carried out in Huantai county, Shandong Province. The result showed that straw incorporation and organic fertilizer application could increase yield and save water clearly. Under the same amount of irrigation(250 mm), the field with all corn and wheat straw incorporation had a higher yield of 885 kg.hm 2 than the field without straw incorporation, and a higher water efficiency of 3.13. The field with all corn and wheat straw incorporation and organic fertilizer application had a higher yield of 1875 kg.hm-2 than the comparing field, with a higher water efficiency of 3.60. The field with wheat straw incorporation had a higher yield of 675 kg.hm-2 than the comparing field, with a higher water efficiency of 3.24. The field with wheat straw incorporation and organic fertilizer application had a higher yield of 1200 kg.hm-2 than the comparing field, with a higher water efficiency of 3.28. PMID- 11767600 TI - [Rational range and optimum proportion of energy input in farmland]. AB - There exists a rational range of artificial supplemental energy inputs in fields. In the range, the inputs can improve the yield and the output/input ratio. The rational range of energy input in total energy output is bigger than that in the output/input ratio. It is bigger in low yield fields than high yield fields, which suggests that increasing artificial supplemental energy input can increase the production of low yield fields as same as high yield fields. In the rational range of energy input, there exist high efficient lines in water and fertilizer inputs. The highest efficiency occurs when the rational inputs of water and fertilizer occur in these two lines. There also exist optimum lines of energy and economy input proportions. In the two lines, the proportions of energy and economy output/input of water and fertilizer inputs are the highest, which are the optimum of water and fertilizer inputs. Water and fertilizer may replace each other for equal yields, but would result in a decrease in the output/input ratio. PMID- 11767601 TI - [Boron balance in agroecosystem on brown-red soil of south Hubei Province]. AB - Five sequential cropping systems including rape/soybean-rice, wheat/watermelon rice, rape/corn-soybean, wheat-sesame and soybean-sesame, were selected study the boron balance in agroecosystem on brown-red soil of south Hubei Province. The results show that the main output of boron was runoff and leaching, which accounted for 48-53% and 41% of the total respectively, while the output by products accounted for 3.4-10.1%. The main inputs were from rainfall, irrigation, fertilization seeds and seedlings, and natural return. PMID- 11767602 TI - [Soil nitrogen and organic matter losses under water erosion]. AB - The results of artificial water-scoured experiment show that with the increase of water-scoured intensity, the losses of nitrate and ammonium in runoff, and those of organic matter and total N in sediment increased greatly, while the enrichment ratios of organic matter and total N in sediment reduced correspondingly. When the soils in gully-hilly loess region were fertilized with same amount of NH4NO3, the ammonium and nitrate loss in runoff was respectively 0.9-3.5% and 8.2-19.7% of the application amount. Nitrate mainly lossed in runoff, not in sediment. The correlation coefficient of soil erosion module, organic matter and total N loss with > 20 microns soil aggregates was -0.8935, -0.7928 and -0.8151, respectively. The content of > 20 microns soil aggregates could be used as an index to differentiate the soil organic matter and total N loss. PMID- 11767603 TI - [Effect of different watering and fertilization on N utilization efficiency]. AB - The comprehensive effects of the timing of watering and N and K fertilization(D), amount of irrigated water(W), and application rates of chemical N and K fertilizers, and farm manure(M) were studied by the design of orthogonal regression rotation with five factors and five levels under dry greenhouse condition. The N utilization efficiency of potato was in order of N > W > D > M > K. Under different application rates of W, N, K and M, the N utilization efficiency was significantly increased with optimum timing of watering and fertilization. When the application rate was low, the timing should be earlier, while it was high, the timing should be later. High application rates of W and N resulted in the best interaction effect, with 57.83% of N utilization efficiency; moderater W and N or low W and N had 29.17-40.99% of efficiency; and high W and low N or low W and high N resulted in the lowest efficiency, with 22.87% and 22.51%, respectively. PMID- 11767604 TI - [Leaching loss of nitrate from semiarid area agroecosystem]. AB - A 6 years lysimeter experiment shows that an obvious nitrate leaching even occurred in semiarid area agroecosystem. The leaching loss was positively related to precipitation, and had a signficant difference among years with different precipitation. The application rate of N fertilizers determined the amount of leaching loss, but no obvious difference was found between urea and ammonium bicarbonate. Different depth of soil had different water storage, and therefore, had different leached amounts. Summer fallowing could increase the potential nitrate leaching loss. PMID- 11767605 TI - [Determination of tannin in cotton plant]. AB - Three methods were used to determine the tannins content in cotton plant tssues. The tannin content in different organs and terminal leaves of four cotton varieties at different growth stages determined by the Folin's assay was nearly two folds as much as that determined by acid butanol assay, indicating that the Folin's assay only offers the total phenol content, but is not suitable for determining the content of condensed tannin in cotton. There was no significant difference between the results of vanillin assay and acid butanol assay, and hence, it is feasible to use vanillin assay to test the tannin content in cotton. Determinations at boll stage showed that the content of condensed tannin in calyx, boll shell and leaf was rather high, generally up to 5-10%, while that in petal, stigma, ovary and inner boll was lower (about 2%). The condensed tannin content in terminal leaf continually increased from seedling(< 1%) to boll stage (10% or so), indicating that the increased tannin content is closely related to the maturity, decrepitude and lignification of cotton tissues. PMID- 11767606 TI - [Adaptation of transgenic strains of insect-resistance cotton to different ecological environments]. AB - Seven transgenic strains of insect-resistance cotton, WH1, WH2, WH3, WH4, WH5, WH6 and BG2, and one common strain Simian-3 (CK) were selected to investigate their adaptation to insect-resistance and yield trait at 10 different sites. The results show that all transgenic strains had a strong resistance to bollworm(Helicoverpa armigera) and pink bollworm (Pectinophora gossypiella), with a high stability and no difference in 10 sites, but the yield trait was significantly influenced by environmental factors. The interaction between strains and sites was significant. In comparison with CK, WH6 and BG2 had a good insect-resistance and high fiber yield, and could be applied in practice. PMID- 11767607 TI - [Isolation and selection of strains used to degrade organic chlorine pesticides and application effects]. AB - With the organic chlorine pesticides (666, DDT) as sole carbon resources, three strains, No. 153 (Bacillus), No. 411 (Achromobacter) and No. 512 (Pseudomonas), which can degrade 666 (BHC), were isolated and selected in Tonomura culture medium. The degradation rates of these strains were 59.6%, 56.9% and 56.0% for total amount of 666, and 55.9%, 57.6% and 56.9% for beta-666, respectively. The other strains, No. 288 (Alcaligenes), No. 410 and No. 411 (Achromobacter) to degrade DDT were also obtained. The degradation rates of the strains were 59.0%, 47.5% and 45.1% for total amount of DDT, and 59.9%, 57.6% and 49.6% for PP'-DDT, respectively. The degradation effects of the mixtures of the isolated strains in pot and field experiments were similar to those of the pure culture, indicating it is a feasible measure to apply the mixture of strains to degrade residual pesticides in fields. PMID- 11767608 TI - [Interaction of Se and S forms in rhizospheric soil and their absorption by tobacco]. AB - Pot experiment with tobacco shows that the amount of total, solube, exchangeable and organic Se in rhizospheric soil appeared depletory, while that of total, adsorbed and organic S appeared enriched. The influence of added S on Se depletion depended on the level of Se application, and that of added Se on S enrichment depended on the rate of S applicagtion. In the absence of added Se, the addition of S decreased the depletion of several Se forms; while in its presence, the reverse result was obtained. The addition of Se increased the enrichment of total S when the S was not added. With S application, the added Se reduced the enrichment of total S. At early stage, teh Se content of tobacco was mainly influenced by the soluble Se in rhizospheric soil, while the accumulated amount of Se in tobacco was also influenced by exchangeable, organic and acid soluble Se. The S content in the aboveground part of tobacco at its early stage was mainly influenced by soluble and organic S in the rhizosphere. PMID- 11767609 TI - [Cu, Co and Se nutritive value of compound trace elements controlled-release boluses for grazing ruminants]. AB - Twenty cattle with the similar old and weight were randomly divided into two groups for 135 d, while twenty white goats were randomly divided into two groups for 60 d. Each group consisted of ten animals, and the ratio of male and female was same. Each of animals in one group was administered an initial bolus, used as treatment group. In the other group, animals were not administered the bolus, used as control group. In the cattle feeding experiment, five cattle of each group was supplemented feed, and the other five cattles were not supplemented feed. In the goat feeding experiment, all of goats were grazing, and not supplemented feed. At the end of goat feeding experiment, three goats of each group were randomly selected to slaughter. Liver, kidney, spleen, muscle, heart, blood and matter in the rumen were collected to assay for Cu, Co and Se. The results showed that the average daily gain of cattle supplemented and no supplemented feeds in the administered and no administered group was 483.00 g, 302.83 g, 445.84 g and 282.23 g, respectively. There had significantly difference between the administered group and no administered group(p < 0.05). The average daily gain of goats in the administered and no administered groups was 68.83 g and 50.67 g, and significant difference between the two groups (p < 0.01). Administering the boluses improved the contents of Cu, Co and Se in the tissues of goats, significantly. PMID- 11767610 TI - [Flood prevention function of Panjin wetland at Liaohe delta]. AB - This paper discussed the character of flood, the change of flood disasters and the flood prevention function of Panjin wetland at Liaohe delta. According to the hydrogeological characters of Panjin wetland and its landscape function in flood prevention and disaster reduction, the Panjin wetland was divided into key prevention area, flood ground-stored area, flood discharged area, emergent flood divresion area, and flood prevention and draining area, which might be a reference to the planning of local development. PMID- 11767611 TI - [Ecological planning and designing in agricultural landscapes]. AB - Based on the theories of landscape ecology, this paper discussed the principles and methods of ecological planning and designing in agricultural landscapes. It is suggested that the ecological planning and designing in agricultural landscapes became an important applied field of landscape ecology, due to the characteristics of microspatiality, and correlation and integration involved problems. The Zhuolu basin, located in the semiarid region of northwest Hebei Province was chosen as a case study. PMID- 11767612 TI - [Preliminary study on purification function of reed wetland for nutrients from land sources]. AB - The preliminary study on purification function of reed wetland for nutrients from land sources were conducted by irrigation channels and lysimeters. The results show that the purification rates for N, P and CODcr are from 41.7%-64.71% in the channels and 60.0%-75.92% in the lysimeters. The contents of N and P reached the national second level standards of sea water after filtration by lysimeters. By harvest, the good recycle between wetland and land is formed without accumulation. PMID- 11767613 TI - [Effect of initial population density on resting egg formation of rotifer Brachionus calyciflorus]. AB - With the method of population accumulative culture, the effect of initial population density on the formation of resting eggs of freshwater rotifer(Brachionus calyciflorus), and on the rates of mictic female and fertilization was studied. During 11 days culture, the productivity and the formation efficiency of resting eggs, and the mean rate of mictic female were the biggest when the initial population density was 1.0-10.0 ind.ml-1, second by the density of 20.0 ind.ml-1, and the lowest by the density of 50.0 ind.ml-1. There was no significant effect of initial population density on the fertilization rate. Statistical analysis on maximum formation efficiency of resting eggs, their emergence and productivity showed that when the production of resting eggs was large-scaled proceeded, the feasible initial population density should be 10.0 ind.ml-1, and the corresponding time should be 6 days to obtain a higher yield of resting eggs and a higher formation efficiency. PMID- 11767614 TI - [Prediction of bioconcentration factors of organic compounds in fish by molecular connectivity indices and function correction factors]. AB - Studies on the prediction models of bioconcentration factors(BCF) of 239 organic compounds showed that the BCFs of polar organic compounds could not be accurately predicted solely by the linear model based on molecular connectivity indices. Additionally, the linear model was not suitable for superphilic compounds. By introducing function correction factors to the model, the residual of the prediction model for polar organic compounds was reduced significantly. When the nonlinear estimation was used, the accuracy of the obtained model was further improved. The final prediction model consisted of parameters (0 chi v)2, (2 chi v)1/2, 2 chi, 3 chi c, 0 chi v and 10 correction factors for function groups OH, NH2, NO2, NCOO, etc. The difference between calculated and observed values of logBCF and its causes were analyzed. The robustness of the model was tested by Jackknifed method, based on random grouping and compound classification. PMID- 11767615 TI - [Uptake of particulate lead via gills of goldfish]. AB - This paper studied the uptake of Pb absorbed on suspended gibbsite via gills of goldfish (Carassius auratus). Under conditions of the concentration of the particulate Pb varied while that of free Pb maintained at a constant level, the levels of both Pb and Al in the gills increased with increasing exposed Pb concentration. The increasing rate (slope 0.171) of Pb level in the blood with the Pb level in the gills was lower than that (slope 0.343) of soluble Pb exposure experiment. Partial Pb adhered on the gills did not transfer into blood. The ratio of Pb/Al in the gills was 1-2 orders of magnitude higher than that in the water, and on the microtome section of filament, the gibbsite particles adhered on gill mucus were observed, indicating the bioavailability of the particulate Pb uptake by the gills of goldfish. The major mechanism was: when the absorbed Pb on suspended particles was flowed into gill filaments, it was desorbed on the surface of gills, and then, passively diffused or transferred by carriers via gill cells into flood, and after the particles stayed on the surface of gill filaments for a short time, in company with sloughed mucus, they were released from the gills along with waterflow. PMID- 11767616 TI - [Gastric evacuation rate of black sea bream(Sparus macrocephalus)]. AB - The gastric evacuation rate of black sea bream(Sparus macrocephalus) weighing 20 40 g was determined at 18 degrees C in laboratory. Three mathematical models were applied to simulate it. The result indicated that all of these three kinds of models fitted to the experiment data, while statistical analysis showed that the linear model was the best, whether the remained food in stomach was expressed by wet weight or dry weight. When the remained food in stomach was expressed by wet weight, the model was Y = 1.14 - 0.06 t(r2 = 0.82, p < 0.001), and by dry weight, it was Y = 1.36 - 0.07 t(r2 = 0.62, p < 0.001). The gastric evacuation rate of black sea bream was 6-7% of consumed food per hour at 18 degrees C. PMID- 11767617 TI - [Comparison analysis on physical and value assessment methods for ecosystems services]. AB - Physical assessment method (PAM) and value assessment method (VAM) for ecosystems services assessment were compared, and their strengths and weaknesses were analyzed. The comparison and analysis demonstrated that in some cases, different, even opposite results will be drawn with these two methods for the ecosystems services assessment of one ecosystem. The functions or effects of PAM and VAM are different for different assessment purposes or different spatial scales, but they will promote and complement each other to some extent. PMID- 11767618 TI - [Genetic variation of geographical provenance of Pinus massoniana--review and analysis]. AB - Pinus massoniana is a significant tree species constituting the subtropical forests in China. Based on morphological, physio-ecological, chromosome, and molecular levels, the genetic variation of geographical provenance of P. massoniana and its distribution were reviewed, and the methodologies on genetic diversity and the genetic variation patterns of geographical provenance of P. massoniana were synthetically analyzed. The Key problems on molecular ecology of P. massoniana were discussed. PMID- 11767619 TI - [Vegetation and erosion control: exploration on basic principle of slope engineering]. AB - During its interaction with local climate and surface and shallow soil, vegetation appears to be of certain hydro-mechanical effects, and provides with some engineering properties on erosion control and slope protection. Slope eco engineering integrates these properties with soil for slope protection projects. Along with the increasing awareness of the interactions between vegetation and soil and their significance in erosion control during the past few decades, this biological approach has been widely applied in physical environment improvement and engineered slope protection world wide. Some important contents in slope eco engineering are the concept of "soil-vegetation system" and the related biological natures and engineering properties. The "soil-vegetation system" concept is a theoretical substance, and its eco-biological natures, engineering properties and some internal regulations are the theoretical hypothesis of the substance, which could be the basic materials for setting up the scientific principles of slope eco-engineering. PMID- 11767620 TI - [Hydraulic architecture and drought resistance of woody plants]. AB - This paper introduced with emphasis the physiological meaning of hydraulic architecture and its parameters, e.g., hydraulic conductivity(Kh), specific conductivity(Ks), leaf specific conductivity(LSC), Huber value(Hv) and water storage capacitance(C), the hydraulic architecture patterns of woods and woody plants, and the developmental trend in their research. The relationship between the hydraulic archteciture of woody plants and their drought resistance was tried to be expounded in mechanism. PMID- 11767621 TI - [Mycorrhizal research on nitrogen-fixing plants]. AB - Advances in mycorrhizal research on nitrogen-fixing plants were introduced. The universality of mycorrhizal formation in nitrogen fixing plants, the reciprocal promotion effect of symbiosis, and the application prospect of mycorrhizal techniques under stressed conditions were summarized and reviewed. The mechanism of enhancing nitrogen fixation of N-fixing plants by mycorrhizal fungi in symbiosis was preliminary discussed. PMID- 11767622 TI - [Research progress on PGPR/AMF interactions]. AB - As one of the rhizospheric microorganisms PGPR(Plant Growth Promoting Rhizobacteria) and AMF(Arbuscular Mycorrhizal Fungi) play an important role in promoting plant growth. It is of significance to further study and elucidate the interactions between them to utilize and regulate the interactions among rhizospheric microorganisms, and promote and protecte plant growth. Many research results show that on one hand, there exists synergism between PGPR and AMF. AMF can transfer PGPR or act as a media in the process of spread of PGPR along roots, where PGPR create many beneficial conditions for the infection of AMF. Both of them can indirectly enhance the other side's colonization or infection ability through their own promoting role on plant growth. On the other hand, they compete with each other for nutrients and niches, and probably produce some secondary metabolites which cause detrimental effects on the other. However, whether these interactions are synergistic or competitive depends upon the AM fungal or PGPR species involved. So far, the research work is extensive, even in molecular level in some aspects, but not systematic and deep. It is believed however, with the development of techniques in molecular biology and the increasing application of advanced testing methods, the new breakthroughs will be gained in the study and understanding on the interactions. PMID- 11767623 TI - [Root excretion and plant resistance to metal toxicity]. AB - Reducing the availability and toxicity of metal pollutants before they enter plant body is one of the main mechanisms of plant resistance to metals. Root system is the first entrance of metal pollutants from soil into plant. It can excrete organic acids, amino acids, sugars, growth substances etc. into rhizosphere. Root excretion affects the metal absorption by plant through changing the physical and chemical characters(such as pH, Eh) of rhizosphere. The metal pollutants are detained outside the roots by chelation, complexation and disposition with root exudates. The quantity and activity of metals in rhizosphere are changed by root exudates through changing the composition, activity and excretion of microbes there. After reviewing the research advances on root excretion and plant resistance to metals, the authors pointed out the existing problems and the major topics and significance of further research. PMID- 11767624 TI - [Nutrient content in litterfall and its translocation in plantation forests in south China]. AB - The amounts of litterfall, nutrient content in it and leaves of five plantation forests in south China were determined. The order of litterfall biomass was in sequence of Acacia mangium (11.1 t.hm-2) > Pinus elliotii (7.3 t.hm-2) > Schima superba (6.5 t.hm-2) > Acacia auriculaiformis (4.8 t.hm-2) > Eucalyptus citriodora (2.6 t.hm-2). A. mangium returned soil much more nutrient to soil through litterfall than other forests did. N, P and K were largely translocated from senescing leaves for all the five forests, and especially for A. mangium. Nutrient translocated varied greatly with seasons. The translocation of other elements was not definite. PMID- 11767625 TI - [A comparative study on chlorophyll content, chlorophyll fluorescence and diurnal course of leaf gas exchange of two ecotypes of banyan]. AB - The morphological differences, chlorophyll contents, fluorescence and diurnal course of leaf gas exchange between terrestrial banyan and amphibious banyan were compared with pot culture. The amphibious banyan possesses well developed aerial and hydro-adventitious roots, and wider leaf with inclination of evolution toward mesophytic traits. The chlorophyll content of terrestrial banyan was higher than that of amphibious banyan. The diurnal course of leaf gas exchange indicated that net photosynthetic rate of terrestrial banyan was slightly higher than that of amphibious banyan grown in water, but much higher than that grown in soil. The amphibious banyan grown in water had the highest transpiration rate, the terrestrial banyan had a lower one, and the amphibious banyan grown in soil had the lowest. Linear regression analysis showed a positive correlation between net photosynthetic rate and stomatal conductance, implying that the stomatal conductance was dominant factor controlling the gas exchange. In this study, the term of intrinsic water use efficiency (net photosynthetic rate/stomatal conductance ratio, Intrinsic WUE) was applied to describe the photosynthesis and water properties, and the result showed that it was a more suitable measure compared to the usual WUE(net photosynthetic rate/transpiration rate). Among the three banyan plants examined, the amphibious banyan had the highest intrinsic WUE. PMID- 11767626 TI - [Life table analysis of Tsuga longibracteata population]. AB - Tsuga longibracteata is a rare and endangered tree species in China. Based on the life table of population and the theory of survival analysis, the authors worked out the life table of Tsuga longibracteata population drew the curves of mortality density function, hazard rate function and survival, and analyzed the population dynamics. The results show that the population had two peaks of mortality, and the survival curve of the population trended to the type of Deevey II. PMID- 11767627 TI - [Structure and spatial pattern dynamics of dominant populations in a natural forest in north Guangdong Province]. AB - Five 1000-m2 plots were set up in a forest dominated by Schima superba, Castanopsis fargesii and Pinus massoniana in Luoba Nature Reserve, Shixing County, north Guangdong Province. Field data were obtained by tally with contiguous grid quadrat method. The analysis of population structure and spatial distribution patterns of the dominant species in the forest shows that S. superba and C. fargesii had a large reserve of seedlings, with up to 1538 and 9763 seedlings per hm2, respectively, showing a pyramid shape of population structure. Both populations had a high mortality for seedlings of classes I and II in the process of development to saplings. The population structure of P. massoniana was an inverse pyramid type, with no seedlings and only 4 saplings per hm2, but 44 large trees per hm2. The spatial distribution patterns of P. massoniana and C. fargesii in coniferous broadleaved mixed community chiefly dominated by broadleaved trees were uniform, and in those chiefly dominated by P. massoniana were aggregated, but there were different causes of pattern dynamics for P. massoniana and C. fargesii. S. superba in both communities showed an aggregated distribution pattern. The aggregation intensity was different, with K values from 0.4280 to 0.9750. Regarding the distribution patterns in different development stages, S. superba was aggregated in different stages, while C. fargesii varied with uniform distribution pattern for the large trees and aggregated distribution pattern for the saplings and median trees. As for P. massoniana, its median trees showed an aggregated distribution pattern, while both the saplings and large trees were uniform. The variations in spatial distribution patterns of populations in different development stages were closely related to the biological and ecological characteristics of the species, but different block size had an impact on the outcome of spatial distribution patterns. PMID- 11767628 TI - [Molecular ecology of Cryptocarya chinensis populations in different communities]. AB - The amplified fragment length polymorphism (AFLP) method was used to analyze two populations of Cryptocarya chinensis, the succession climax species in lower subtropical broadleaved forest. The across two communities of evergreen broadleaved forest and mixed coniferous-broadleaved forest. The analysis of molecular variance (AMOVA) indicated that the genetic variation was mostly due to the difference within individuals of the population (89.55%), with high significant genetic variation (10.45%) due to the different communities. The microenvironment of different communities and population biological characteristics resulted in the genetic divergence. PMID- 11767629 TI - [Evaluation on soil anti-erodibility of soil and water conservation forest]. AB - Indexes including organic matter content, water stable aggregate content, mean weight diameter of water stable aggregate, aggregate degree and disperse coefficient were selected to evaluate soil anti-erodibility of soil and water conservation forests component of different tree species at different ages. The results showed that soil and water conservation forest played an important role in improving soil anti-erodibility, especially to the topsoil. Compared with that of Chinese pine pure forests, Chinese pine-broadleaved mixed forests had higher soil organic matter content, and water stable aggregate content increased by 1.71%-38.53%, and soil anti-erodibility was also increased with increasing stand age. PMID- 11767630 TI - [Ecological process of vegetation restoration in Caragana mirophylla sand-fixing area]. AB - The occurrence and development of artificial vegetation after mobile sandy dunes being fixed by adopting straw check combining with seeding Caragana microphylla were studied. Especially the process of species invasion and the changes of community structure in 35 years were analyzed in detail. The results showed that the species richness of artificial community of C. microphylla increased, from 5 species (in 2 years) to 23 species in 35 years. In the structure concerning plant lifeform, therophytes were in dominant position, while the ratio of therophytes to all plant species had a tendency of decrease. The rates of species number and the quantity of hemicryptophytes and geocryptophytes increased gradually. Species diversity and community evenness indexes increased and ecological dominance index decreased gradually. The similarity index of the artificial plant community to natural one increased with age. The changes of physical and chemical property of soil were also discussed. PMID- 11767631 TI - [A mechanistic model of phasic and phenological development of wheat. I. Assumption and description of the model]. AB - The temperature effectiveness for wheat development was non-linearized and the apical and phenological development stages were systematically predicted by the scale of physiological development time which was based on the ecophysiological development process. The predicted apical development stages included single ridge stage, double ridge stage, floral initiation stage, stamen and pistil initiation stage, anther seperation stage, tetrad stage, and heading stage, while the predicted phenological development stages included germination stage, emergence stage, tillering stage, winterovering stage, green-turning stage, jointing stage, booting stage, heading stage, flowering stage, grain filling stage, and maturity stage. Four cultivar specific parameters were used to describe the genotypic differences of wheat development. They were temperature sensitivity, physiological vernalization time, photoperiod sensitivity, and intrinsic earliness, reflecting the genetic properties of different cultivars in thermal effectiveness, vernalization, photoperiod response and shortest time required for reaching flowering, respectively. The four parameters determined the physiological development time required for each development stage of different cultivars. PMID- 11767632 TI - [Dynamics of soil P pool in a long-term fertilizing experiment of wheat-maize rotation. I. Crop yield effect of fertilizer P and dynamics of soil total P and inorganic P]. AB - The effects of long-term applying fertilizer P and manure on the pools of soil total P and inorganic P and the crop yield in rotation of winter wheat-summer maize-->spring maize were studied. The results showed that the pool of soil total P and inorganic P were increased by applying fertilizer P and manure, and the phosphorus mostly accumulated in soil was inorganic P. The critical amounts of fertilizer P (P2O5) for balancing soil P were 94.7 kg.hm-2 to winter wheat-summer maize and 51.5 kg.hm-2 to spring maize. Based on regression equations, the application rates of fertilizer P (P2O5) for economic optimum and highest yields were 135.8 and 149.8 kg.hm-2 to winter wheat-summer maize, and 88.6 and 95.9 kg.hm-2 to spring maize, respectively. PMID- 11767633 TI - [Dynamics of soil P pool in a long-term fertilizing experiment of wheat-maize rotation. II. Dynamics of soil Olsen-P and inorganic P]. AB - Studies on the dynamics of soil Olsen-P and different form inorganic P in the long-term fertilizing experiment of winter wheat-summer maize-->spring maize rotation showed that the contents of Olsen-P and inorganic P were changed by the accumulation and consumption of P in soil. In P0 treatments, Olsen-P decreased gradually, and then, trended to the critical level. When fertilizing amount was basically equal to the intake by crops, the balance of Olsen-P was dynamically maintained. The contents of Olsen-P and inorganic P were enhanced, when applied P was larger than the P intake by crops. The major contents of residual inorganic P were Ca2-P and Ca8-P, both accounting for 52.3% of total inorganic P in average, and Ca8-P accounting for 78.3%. Al-P and Fe-P accounted for 26.1%, and O-P and Ca10-P accounted for 20.4% of total inorganic P. The availability of fertilizer P was obviously increased by long-term applying fertilizer P together with manure, compared with applying fertilizer P alone. PMID- 11767634 TI - [Two-phase linear models of leaf emergence at different tillering positions in wheat and effects of different varieties and sowing dates]. AB - Dynamics of leaf emergence shows the development progress and its relationship with growth in wheat. It was found that two-phase linear model equations (phase I faster than phase II) divided by glum differentiation stage could describe leaf emergence progress in relation to growing degree days (GDD) after sowing in wheat. This pattern was consistent in main stems and tillers of normal development with both winter-and-spring type varieties. The beginning of phase II shifted to an earlier development stage on main stems of winter type varieties of early planting (EP, September 30) and late planting (LP, March 2), and on T3 of both varieties of EP, MP (middle planting, on October 30) and LP due to their abnormal development. The thermal rate of leaf emergence on main stem was relatively high and steady during development for winter type variety of MP, and quickened with the postponing of sowing for spring type variety. The above results illustrated the difference of leaf emergence at different tillering positions, and the biological characteristics affected by different varieties and sowing dates. PMID- 11767635 TI - [Nutrition of wheat under wet injury and its regulation]. AB - With pot experiment, this paper dealt with the effects of different nutrition regulations on nutrient absorption and crop yield of wheat under waterlogged condition. N, P, K, Zn, Cu uptakes by wheat were greatly inhibited by waterlogging. The total amounts of reusable elements N, P, K and Zn in leaves decreased obviously in stems but did not in ears, compared with control; while the total amount of element Cu in all parts was reduced by waterlogging. The yield of individual wheat plant was significantly reduced under waterlogging. Additional N-fertilizer or spraying N, P and K significantly increased the uptake of nutrients and the yield for Wanmai 19 under light waterlogging, but were not effective for Yanmai 158 under heavy waterlogging. A positive correlation was found between the yield of wheat under waterlogging and the N accumulation in leaves. PMID- 11767636 TI - [Effects of soil moisture and shading levels on photosynthetic characteristics of cotton leaves]. AB - The effects of different soil moistures and shading levels on stomatal conductance(Gs), net photosynthetic rates(Pn), transpiration and leaf water potential(LWP) of cotton (variety Zhongmian No. 23) grown in pots from the seedling to flower bud stages in summer noon were evaluated. We designed three shading levels: no-shading(CK), 75% shading (DN), 40% shading(SN); and three soil moistures; 85%-100% (high water, HW), 65%-85% (medium water, MW) and 45%-65% (low water, LW) of field water-bolding capacity. The Gs of DN and SN increased by 16.69% and 28.01% compared with CK at HW, respectively, while the Pn of DN and SN declined by 45.74% and 20.54%, respectively. The Gs of DN and SN enhanced by 28.86% and 23.28% compareds with CK at MW, respectively, while the Pn of DN and SN decreased by 31.97% and 1.64%, respectively. The Gs of CK, DN and Sn did not exhibit significant differences at LW, while Pn of DN and SN reduced by 46.22% and 13.45%, respectively. Significant difference in Gs did not exist between DN and SN at the same soil moisture, but there was significant difference in Pa between them (except at LW). It was suggested that Gs declined with the increasing of leaf-to-air vapor pressure difference (VPD) and showed weak correlation with Pn by regression. The combined effects of soil moistures and shading levels on LWP and transpiration rate were not significant. There was no significant difference in LWP and transpiration rate among three shading treatments. Contrasted to treatment CK, intercellular CO2 concentration (Ci) in DN and SN at HW, MW and LW increased significantly, except no apparent change of Ci in SN at MW. PMID- 11767637 TI - [Effect of lanthanum on growth and biochemical property of Sclerotinia sclerotiorum]. AB - The study shows that La2O3 at a concentration of 30-450 mg.L-1 could inhibit the growth of S. sclerotiorum in both solid and liquid media and the inhibition effect was increased with its increasing concentration. The activity of pectinase produced by S. sclerotiorum in liquid medium was also increased with increasing La2O3 concentration. PMID- 11767638 TI - Production and reduction of nitrous oxide in agricultural and forest soils. AB - A soil-water slurry experiment was conducted to study the potentials of N2O production and reduction in denitrification of agricultural and beech forest soils in Denmark. The effects of nitrate and ammonium additions on denitrification were also investigated. The forest soil showed a higher denitrification potential than the agricultural soil. However, N2O reduction potential of the agricultural soil was higher than the beech forest soil, shown by the ratio of N2O/N2 approximately 0.11 and 3.65 in the agricultural and the beech forest soils, respectively. Both nitrate and ammonium additions stimulated the N2O production in the two soils, but reduced the N2O reduction rates in the agricultural soil slurries. In contrast to the effect on the agricultural soil, nitrate reduced the N2O reduction rate in the beech forest soil, while ammonium showed a stimulating effect on the N2O reduction activity. After one week incubation, all of the N2O produced was reduced to N2 in the agricultural soil when nitrate was still present. Nitrous oxide reduction in the beech forest soil occurred only when nitrate almost disappeared. The different nitrate inhibitory effect on the N2O reduction activity in the two soils was due to the difference in soil pH. Inhibition of nitrate on N2O reduction was significant under acidic condition. Consequently, soil could serve as a sink of atmospheric N2O under the conditions of anaerobic, pH near neutral and low nitrate content. PMID- 11767639 TI - [CO2 release from typical Stipa grandis grassland soil]. AB - Determinations on the soil respiration in a typical Stipa grandis grassland of Inner Mongolica by the method of static chamber/alkaline absorbing show that there existed great spatial and temporal variances of soil respiration, and the factors controlling these variances were different. The seasonal variance of soil respiration had a close relationship with the aboveground biomass of S. grandis and the status of soil moisture. The total amount of annual CO2 release in 1995, 1997 and 1998 was estimated as 180, 45.8 and 225 gC.m-2.yr-1, respectively. Overgrazing greatly decreased the biomass of the community, and also, decreased the CO2 release from the soil. The possibility of establishing a dynamic model of soil respiration in grassland with precipitation as a driven factor was discussed. PMID- 11767640 TI - [Influence of plant species diversity on productivity of sandy grassland in Kerqin Region]. AB - The relationship between species diversity indices and sandy grassland productivity was studied in Kerqin sandy land, and the results showed that the relations could be divided in to two categories based on the indices and productivity. The first type includes function and composition diversities, their maximal biomass varied form 299 to 336 g.m-2, and had a simple linear relation with the productivity. Their correlation coefficient was remarkably significant. The species richness and Shannon-Wiener indices attribute to second type, their maximal biomass varied from 426 to 433 g.m-2, and had a complex parabola relations with the productivity. Their correlation coefficient was also significant. Meanwhile, the grey correlation analysis showed that the species composition diversity index was the most important factor that influences productivity. According to the grey correlation degree, the order of the different indices affecting productivity was: composition diversity(0.74), function diversity (0.72), species richness (0.66) and Shannon-Wiener index (0.14). It is suggested that increasing plant species richness (species introduction) and consequent composition diversity could be the practices of improving the degraded grassland in Kerqin. PMID- 11767641 TI - [Effect of grazing on reproduction in Leymus chinensis population]. AB - The experiment on the effect of grazing on the asexual and sexual reproduction and biomass allocation in Leymus chinensis population was conducted in Songnen grassland. The results show that animal grazing reduced both asexual and sexual reproductive channels. With the increase of grazing intensity, the densities of asexual shoots and rhizome tillers, seed biomass, numbers of seeds per inflorescence and sexual shoot ratio decreased significantly, especially after heavy grazing. The rates of biomass allocation to rhizome increased significantly with increasing grazing intensity, while the rates of biomass allocation to assimilation, unassimilation organs and seed production decreased remarkably. In the haviest grazing stage, there were almost no sexual shoots. PMID- 11767642 TI - [Age structure of tillers of Hordeum brevisulatum clone in Songnen plain of China]. AB - The tillers of Hordeum brevisulatum clone have a significantly expanding age structure, which includes three age classes. The 1st age class tillers are absolutely dominant in the reproductive growth of the clone. The older the tillers, the smaller the rate of quantitative increase, and the less the accumulative nutrients are. The quantity and biomass of the 1st and 2nd age classes increase with the size and the tiller number of the clone, while the 3rd age class tillers are positively linearly interrelated to the total tillers of the clone. The mean weight per tiller decreases with the age class increased. The mean weight per reproductive tiller is relatively constant among three age classes, and that of the 1st tillers of clone has a negative respondence to the density of tiller. The age structure of the potential population of clone is also of an obviously expanding type. The buds on the vegetative tillers are always more than those on the reproductive tillers. The buds on the vegetative or reproductive tillers of every age class are all positively interrelated to the size and the total tillers of clone. PMID- 11767643 TI - [Beta-diversity of Stipa communities in Inner Mongolia Plateau]. AB - The beta-diversity characteristics of four Stipa communities (S. baicalensis, S. grandis, S. krylovii and S. klemenzii) were studied using comparable plots methods. As a measurement of species turnover within communities, Whittacker's index(beta ws) was size-dependent, and reduced gradually with the increasing quadrat size. Under the same scale, beta ws indices of the communities were similar. Cody's index (beta c) was also affected by sampling size. beta c increased initially as quadrat size enlarged, then stabilized over the size of 0.5 m2 for S. baicalensis and S. grandis communities, and 2 m2 for S. krylovii and S. klemenzii communities. S. baicalensis community had the highest Cody index, while S. klemenzii community had the lowest one. In most cases, the within community distance interval had a relatively high effect on Cody index; From S. baicalensis to S. klemenzii community, the functional group diversities of forbs, perennial bunch and rhizome grasses decreased greatly, the diversity of intermediate xerads reduced significantly, and the diversity of xerads increased firstly, and then declined for S. klemenzii community. The changes in species composition of four Stipa communities could give a reflection to the degrees of community replacement along ecological gradients, and Cody indices between the communities reduced gradually. The Morisita-Horn similarity coefficient between S. baicalensis and S. grandis community was significantly higher (0.72) than those between S. grandis and S. krylovii communities (0.55), and between S. krylovii and S. klemenzii communities(0.42). PMID- 11767644 TI - [Behavior response of four Leis axyridis varieties to volatiles from tea and Toxoptera aurantii]. AB - The behavior response of the adults of four Leis axyridis varieties to kairomone from Taxoptera aurantii was determined by Y-shape olfaction instrument. The results showed that when supplied with two-two-combinations of Taxoptera aurantii, Brevicoryne brassicae and Lipaphis erysimi, tea aphids plus aphid damaged vs. normal shoots, and aphid-damaged vs. normal shoots, Leis axyridis had a preference for tea aphids, tea aphids plus aphid-damaged tea shoots, or aphid damaged tea shoots. There existed a Logistic curve relationship(P < 0.01) between odor source tendency rate of Leis axyridis and odor source quality, when 8-9 kinds of odor gradients including tea aphids plus aphid-damaged tea shoots, aphid damaged tea shoots and tea aphids were used as odor sources. The tendency rates of Leis axyridis ab. bimaculata, Leis axyridis ab. conspicua and Leis axyridis var. novemdecimpunctata showed single left-tilting peak curves to the aphid number(P < 0.01). Ether and n-hexane ringes of Toxoptera aurantii body surface also showed an attraction to all varieties. Leis axyridis var. spectabilis was the most sensitive variety. PMID- 11767645 TI - [Grey system analysis on dominant natural enemies influencing Aphis gosspyii population]. AB - The populations of Aphis gosspyii and its natural enemies before cotton boll stage were investigated systematically in 1983, 1984, 1986, 1988, 1994 and 1995. The relationship between daily total predation of natural enemies and Aphis gosspyii population size was studied with the grey system theory and method, and the relational grade of various natural enemies to ideal superior natural enemies was analyzed. The results show that Propylaca japonica was the major natural enemy influencing Aphis gossypii, followed by Chrysopa septempunctata, then by Therdion octomaculatum and Erigonidium graminicola. PMID- 11767646 TI - [Geostatistical analysis on spatial patterns of Aphis gossypii and Propylaca japonica]. AB - The spatial construction and distribution of Aphis gossypii and Propylaca japonica at different period were investigated with geostatistics. The results showed that the semivariogram of Aphis gossypii was described by spherical model, indicating an aggregated spatial arrangement, the range was 8.21-10.81 m. The semivariograms of Propylaca japonica was fitted by spherical model too, also indicating an aggregated spatial arrangement, its range was 8.01-14.25 m. The amount and spatial distribution of Propylaca japonica was closely related to that of Aphis gossypii. It reveals that Propylaca japonica is dominant natural enemies of influencing population of Ahphis gossypii. PMID- 11767647 TI - [Effect of plumular axis-cutted cotton on growth and development of cotton bollworm]. AB - The method of plumular axis cutting was used to induce the resistance of cotton plants to cotton bollworms(Heliothis armigera). The bollworm was cultured in the laboratory, and the effect of induced cotton on the duration of larval development and weights of larvae and pupae was studied. In the treatments of infection and control, the lengths of larval period were delayed by 3 days and 0.5 days, the weights of larvae were decreased by 19.60% and 11.45%, and the pupae weights were decreased by 10.81% and 6.54%, respectively. After the 8 days old larvae were reared with induced cotton leaves for 3 days, the infected and uninfected cutted plants resulted in a decrease of the relative growth rates of larvae by 22.9% and 17.2% respectively, and in a decrease of the relative feeding rates by 26.1% and 21.4% respectively. It is suggested that plumular axis cutting could induce the resistance of cotton plants to bollworm, and influence the growth and development speed of bollworms through retarding their feeding and digestion. Combining with the treatment of Pseudomona gladioli D-2251 strain could obviously increase the insect-resistance of cotton plants. PMID- 11767648 TI - [Community characteristics of soil ciliated protozoan at Dapeng Peninsula]. AB - With the qualitative and quantitative analysis, the community characteristics of soil ciliated protozoan sample from Dapeng Peninsula, Guangdong province was studied. The comunity consisted of 42 species of ciliates, including 4 new records in China. The major species were Cohnilembus vexillarius, Colpoda henneguy, Clopoda steinii, Histriculus muscorum, Gonostomum affine, Drepanomonas revolata, Leptopharynx costatus and Dileptus alpinus. Culturing the ciliated protozoan in laboratory showed that the species succession of domimant speies during the culture was from Gonostomum affine and Histriculus muscorum n the early stage to Cohnilembus vexillaria, and then to Colpoda spp. The difference of soil cliated communities between in Dapeng Peninsula and other regions was compared, and the possible factors affecting the difference were analyzed. PMID- 11767649 TI - [Effect of rhizospheric environment of VA-mycorrhizal plants on forms of Cu, Zn, Pb and Cd in polluted soil]. AB - Maize (Zea mays L.) was inoculated with or without VA mycorrhizal (Glomus mosseae) and cultivated in a heavy metals contaminated soil. The distribution and dynamics of Cu, Zn, Pb and Cd forms in rhizosphere of maize inoculated with or without VA-mycorrhizal were analyzed with the technique of sequential extraction. Comparing with control soil, exchangeable Cu in rhizospheric soil increased significantly, and the exchangeable Cd trended down. In rhizosphere of VA mycorrhizal maize, the amounts of Cu, Zn and Pb bound to organic matter were significantly higher than those in rhizosphere of non-mycorrhizal maize, while the four tested metals bound to carbonates and to iron and manganese oxides were constant in rhizosphere of mycorrhizal and non-mycorrhizal maize. These results illustrated that the plant roots could influence the distribution and dynamics of metal forms in rhizosphere, and much for mycorrhizal plants than for non mycorrhizal plants. At excessive concentration of soil metals, mycorrhizal roots might decrease the bio-availability of toxic heavy metals by changing their forms. The factors that caused the change of metal fractions in rhizosphere of mycorrhizal and non-mycorrhizal plants were also discussed. PMID- 11767651 TI - [Assimilation efficiency of pacific oyster Crassortrea gigas]. AB - The effects of body size, food density and its quality on assimilation efficiency of pacific oyster (Crassostrea gigas) were studied under artificial conditions in laboratory. The experimental results show that the filtration and ingestion rates of pacific oyster increased with its body size, which tallied with power function. The assimilation efficiency of pacific oyster was not significantly correlated with its body size, but correlated positively with the organic matter content of food and negatively with food density. PMID- 11767650 TI - A preliminary approach on mass-balance ecopath model of the Bohai Sea. AB - A Bohai Sea mass-balance ecopath model is constructed on the basis of fisheries resources data from the ecosystem survey conducted from April 1982 to May 1983. It is the first ecopath model which consists of 13 function groups (boxes), and only covers the main trophic flow in the Bohai Sea ecosystem. P/B and Q/B parameters (P: production, B: biomass, Q: consumption) for most groups were estimated from similar function groups in other ecopath models of the same latitude regions around. The value of EE (Ecotrophic Efficiency) is the main parameter to check the equilibration of the model. The EE parameters in the model are of high value (> 0.808) for most groups, because the fishing pressure was very high and small living organisms were being heavily preyed upon in the ecosystem. The biomass density of the species commercially utilized estimated by the model is 12.33 ton.km-2. Even though the value is low compared with the density in other ecosystems, such as Caribbean coral reef ecosystem and the Southern B.C. shelf model, it is higher than the value published by some papers on the Bohai Sea using other methods. Considering the lower value estimated by the stock assessment using bottom trawl survey data, the output here is reasonable. It is concluded that the biomass of commercial fishing species in the sea is 950 thousand metric tons, and 338 thousand tons are fish species in the value. PMID- 11767652 TI - [A preliminary study on influence of N and P on population constituent of planktonic diatoms in seawater]. AB - Experiment was conducted to study the influence of N and P on population constiuent of planktonic diatoms in seawater. The concentrations of N and P and their ratios might significantly affect the population constituent of planktonic diatoms in seawater, the more the concentrations of N and P and the bigger the N/P ratio to Redfield ratio, the less the species of planktonic diatoms and Shannon's index. The experimental result was verified in the investigation from shrimp culturing ponds. PMID- 11767653 TI - [Effects of salinity and alkalinity on plankton and water chemical factors]. AB - This paper dealt with the effects of increasing salinity and alkalinity on the chemical and hydrobiological factors in saline-alkaline ponds. The experiment was conducted in Daluhu Aquaculture Company, Gaoqing County, Shandong Province during July and August, 1998. Raw salt and NaHCO3 were used to adjust the salinity and alkalinity. The results showed that increasing alkalinity from HCO3- rsulted in the reduction of pH value, calcium ion concentration and COD in a short term. When alkalinity was increased from 6.64 +/- 0.40 to 13.47 +/- 0.31 mmol.L-1, no significant effect on plankton was observed. However, when salinity was increased from 2.10 +/- 0.22 to 11.29 +/- 0.99 g.L-1, it decreased the plankton biomass, species number and diversity index decreased, and affected the composition of plankton community structure. PMID- 11767654 TI - [Concept of ecosystem management and its essential elements]. AB - Ecosystem management originates from the tradition fields of natural resources management and utilization, and develops in the 1990's. Based on our best understanding of the ecosystem composition, structure and function, and in definite spatiotemporal scales, it integrates human values and social-economic principles into managing ecosystems to resotre and/or sustain ecosystem integrity and sustainability. Ecosystem management requires the collection of field data and the monitoring of ecosystem dynamics at multiple scales. The essential elements of ecosystem management include clear management goals, definite ecological boundaries and units, sound ecological understanding, appropriate scale and hierarchic structure, understanding of ecosystem uncertainty, adaptive management, cooperation between agency and individuals, and viewing human and its value as ecosystem components. The goal of ecosystem management focuses on ecosystem sustainbility. PMID- 11767656 TI - [Plant functional type and its significance in ecological research]. AB - In recent years, plant functional type is a new ecological concept introduced in the research of global change. This paper reviewed the definition, classification, ecological significance of plant functional type. The theories and methodologies of systematic biology were used to understand the concept of plant functional type. And finally, the significance of this term in ecological studies, especially its role in the study of global change and terrestrial ecosystem was explained. PMID- 11767655 TI - [Primary research on interface ecology in agroforestrial ecosystems]. AB - In this paper, the fundamental conception, major research content of interface ecology and its application in agroforestrial systems were discussed. The action mechanism between trees and crops in agroforestrial systems mainly embodied aboveground interface for competitve light, quantity of heat and water, and underground interface for competitiye nutrient and water. It was showed in the interchange and transmission of nutrient, energy and information through interface. PMID- 11767657 TI - [BIOME 6000 Project: latest advances of reconstructing palaeobiome]. AB - Global change research needs the data about the past states of the Earth system, e.g., the pollen and plant macrofossil records for specified time slices (for example, the mid-Holocene interval, ca 6,000 aBP, and the last glacial maximun, LGM, ca 18,000 aBP). In the past, the utilization of these palaeoecological data is mostly scattered and point-fixed, and the reconstruction of palaeovegetation is often qualitatively descriptive. The establishment of international collaboration project BIOME 6000 (a global palaeovegetation mapping program) of the International Geosphere-Biosphere Project (IGBP) breaks a new approach for the synthesis and quantitative study of palaeoecological data. In the projescts The methodology of biomization for assigning palaeoeclogical records to biomes is emphasized, in which, plant pollen taxa are assigned to one or more plant functional types (PFTs) by collecting widely global palaeoecological records which have quality assurance, and by using PFT definition based on the principles of modern ecology. Through combining PFTs into biome types, the global synthesis of biomes reconstructed by using palaeoecological data can be realized. The biomization method might provide a benchmark for coupled atmosphere-biosphere. This trend will facilitate biome mapping for other time slices, and co-evolution of atmosphere-biosphere modeling and palaeodata synthesis and analysis will continue. PMID- 11767658 TI - [Some comments on ecological field]. AB - Based on the data of plant ecological field studies, this paper reviewed the conception of ecological field, field eigenfunctions, graphs of ecological field and its application of ecological field theory in explaining plant interactions. It is suggested that the basic character of ecological field is material, and based on the current research level, it is not sure whether ecological field is a kind of specific field different from general physical field. The author gave some comments on the formula and estimation of parameters of basic field function ecological potential model on ecological field. Both models have their own characteristics and advantages in specific conditions. The author emphasized that ecological field had even more meaning of ecological methodology, and applying ecological field theory in describing the types and processes of plant interactions had three characteristics: quantitative, synthetic and intuitionistic. Field graphing might provide a new way to ecological studies, especially applying the ecological field theory might give an appropriate quantitative explanation for the dynamic process of plant populations (coexistence and interference competition). PMID- 11767659 TI - [Advance in soil sampling methods in rhizosphere microzone study]. AB - Soil sampling methods in rhizosphere microzone study since 1960's were reviewed. It was suggested that the trend of rhizosphere soil sampling was from field coarse sampling to fine division of indoor simulated experiment. The simulated equipment was applied for field experiments, and the purpose guiding production practice could be achieved finally. Meanwhile, with the widening of the concept of rhizosphere, such as ecoboundary layer, rhizosphere soil sampling tends to keep unvarnished and fine. PMID- 11767660 TI - [Forest ecosystem services and their ecological valuation--a case study of tropical forest in Jianfengling of Hainan Island]. AB - This paper attempts to present forest ecosystem services and their indirect economic value of Jianfengling tropical forest in Hainan Island. The results show that average annual integrated ecosystem service value of Jianfengling tropical forest, which covers 44667.00 hm2, adds up to 664.38 million yuan(Chinese RMB), of which, about 71.64 million yuan is of the output of standing trees and other forest products, about 394.29 million yuan of water-holding, about 2.47 million yuan of soil conservation against erosion, about 13.16 million yuan of carbon fixation for reducing green house effect, about 4.29 million yuan of nutrient retention for N, P, K, Ca and Mg, about 178.53 million yuan of air purification. PMID- 11767661 TI - [Tree species diversity in gaps of different sizes and developmental stages in lower subtropical evergreen broadleaved forest, South China]. AB - The change pattern of tree species diversity in gaps of different sizes and developmental stages in the lower subtropical evergreen broadleaved forest was analyzed in this paper. The species diversity index(Shannon-Wienner) did not change in the gaps with a size of < 400 m2, reached the highest in those with a size of 400-500 m2 and the lowest in the gaps of 500-600 m2 size, and increased in those with a size of > 600 m2. The index was the highest in the middle period of 20-50 years, secondly high within 20 years, and lowest after 50 years of gap formation. The species diversity in regeneration layer(H < 1.5 m) reached a peak in the gaps with a size of 500-600 m2, and the lowest values occurred at the gaps with a size of > 600 m2 and 200-300 m2. Species diversity index in the regeneration layer reached the highest in the first 10 years after gap formation, then revealed a general trend of decreasing, but two relative peaks were formed in the gap ages of about 30-40 years and 50-60 years, respectively. The general trends of species richness were correspondent with those of species diversity index. Gaps of different sizes and ages had a strong influence on the tree species regeneration through changes of ecological factors in gaps, thus, tree species diversity was different in gaps of different sizes and ages. Gap is one of the most important mechanisms for the maintenance of tree species diversity in the lower subtropical evergreen broadleaved forest. PMID- 11767662 TI - [Yi nationality's sacred groves and biodiversity conservation in Chuxiong, Yunnan]. AB - Sacred groves occur in many ethnic minority areas of Yunnan, China, which have ecologically multiplex functions and effects on biodiversity management and conservation at grassroots level. In this paper, an extensive field survey was carried out to evaluate the role of the sacred groves of the Yi nationality in Chuxiong of Yunnan. Three forest communities (sacred grove, common forest and natural reserve) under different management were sampled, and their plant species diversity was compared. The result shows that the total species, endemic species and Shannon-Wiener index in the sacred grove community were respectively 67, 17 and 2.96, higher than those in natural reserve (44.8 and 2.17) and common forest (34.4 and 2.39). The sacred groves of the Yi nationality in Chuxiong of Yunnan play an important role in local biodiversity conservation and management. PMID- 11767663 TI - [Relationship between human activities and survival of rare and endangered species Davidia involucrata]. AB - In recent years, the increasing intensity of human activities and the increase of regional developing items led to a sharp decrease of natural distributed area and natural population number of rare and endangered species Davidia involucrata, and now, its natural distributed population is on the point of extinction. This paper analyzed the geographic distribution situation of Davidia involucrata in different geologic and historical periods, and discussed the major reasons for forming the geographic distribution and dynamic changes of population. Through many field investigations and references, some protecting measures were presented. PMID- 11767664 TI - [Stable carbon isotope characteristics of some woody plants in warm temperate zone]. AB - It was found that the delta 13C values of the foliar, trunk, flower, and fruit of some woody plants in broad-leaved forest in warm temperate zone were affected by many factors, and showed a great interspecific difference and temporal and spatial heterogeneity. The intraspecific variation of delta 13C values was also great, with the order of Vitex negundo var. heterophylla 6.549@1000(-22.226@1000( )-28.775@1000), Fraxinus rhynchophylla 5.706@1000(-23.687@1000(-)-29.393@1000), Jugans mandshurica 5.229@1000 (-26.146@1000-31.375@1000), Quercus liaotungensis 3.333@1000 (-24.324@1000(-)-27.657@1000), Syringa pekinensis 2.414@1000( 25.655@1000(-)-28.070@1000), and Prunus armeniaca var. ansu 2.296@1000 ( 23.436@1000(-)-26.432@1000). Different organs of the same species had different delta 13C values: trunk and root barks had the low, while xylem had the highest delta 13C value. According to the relationship analysis between delta 13C value of Prunus armeniaca var. ansu xylem and environment factors, it was found that delta 13C value was strongly affected by annual mean temperature and followed by annual precipitation, mean temperature and precipitation in growth season. PMID- 11767665 TI - [A comparative study on nutrient accumulation and distribution of different generations of Chinese fir plantations]. AB - The nutrient accumulations and distribution of different generation of Chinese fir plantations in central production areas of China were studied through the investigation of plantation with different generation(first, second and third), ages (5, 10, 15, 20 years old) and sites(site index 14, 16 and 18). The nutrient accumulations and distribution of Chinese fir plantations were greatly influenced by the number of planting generation. Nutrient accumulation and utilization efficiency in tree layer of Chinese fir plantations declined with the increasing planting generation number, with the first generation > the second > the third; while the nutrient accumulation of understory vegetation was increased with the increasing of planting generation number. Compared with the first generation plantations, nutrient accumulation of tree layer of the second and the third generations decreased by 17.56% and 36.24% respectively, and the third generation platation decreased by 22.65% than the second generation. Meanwhile, successive planting resulted in a decreasing nutrient utilization efficiency of Chinese fir plantation, and an increasing nutrient necessary for dry matter production per unit, which is disadvantageous to the maintaining of soil fertility, but beneficial to the nutrient accumulation of understory vegetation. PMID- 11767666 TI - [Seed growth characteristics of Ginkgo biloba and its physiological change]. AB - The length, width, volume and weight of Ginkgo biloba seed were measured, and the concentrations of water, sugars, fatty acids and amino acids in seed growth process were analyzed. A typical "S" seed growth curve was found, and the length, width, volume, weight and absolute water content all showed the similar changes during growing period. With the growing of ssed, the concentrations of physiological substances in seeds showed regular changes and had their own characteristics. The total amount of sugars appeared to be an increasing trend at the later stage of seed growth, indicating that sugars are the main nutrition substance accumulated in seeds. The concentrations of various substances in matured seeds were starch 8.4%, glucose 6.7%, fructose 4.2%, polysaccharide 0.02%, disaccharide 0.01%, myristic acid 10.6%, palmitic acid 4.1%, flax acid 2.4%, stearic acid 1.9%, oleic acid 1.1%, and linoleic acid 0.4%. Fifteen types of free amino acids were detected in matured seeds, with total content of 1.56 g.100 g-1FW. Among them, lysine aspartic acid, alanine, arginine, histidine, glutamic acid, and isoleucine were dominant, and their concentrations were 0.287%, 0.163%, 0.136%, 0.133%, 0.123%, 0.115%, 0.095%, respectively. PMID- 11767667 TI - [Simulation of potential responses of clear-cut of mixed coniferous and broadleaved Korean pine forest in Yichun to climate change by BKPF model]. AB - The potential responses of forest succession in the clear-cut site of mixed coniferous and broad-leaved Korean pine forest (MCBLKPF) in Yichun, Heilongjiang Province to global climate change and elevated CO2 after 50 years by BKPF model were simulated. The results indicated that the densities of Pinus koraiensis and hardwood species(Fraxinus mandshurica, Tilia amurensis, Juglans mandshurica and Phellodendron amurense) would increase, while the densities of Larix olgensis, Betula platyphylla and Populus davidiana would decrease after 50 years. The stand densities would be slightly lower than those at the same age under the current climate condition. The stand productivity, total aboveground biomass and leaf area index will increase by 7-28%, 15-24% and 5-8%, respectively. Climate change would be beneficial to the forest succession from the clear-cut site to MCBLKPF. PMID- 11767668 TI - [Effect of flooding stress on transpiration of poplar I-69/55]. AB - The rates of transpiration(Tr) and photosynthesis(Pn) of poplar I-69/55 trees were measured under flooding stress. Flooding stress caused Pn and Tr decreasing, while in the period of measurement, Pn almost didn't change. The longer the period of flooding stress was, the more the Tr and stomatal conductance (Gs) decreased. Undre no stress, Pn and Tr of test trees displayed daily double-peak curves and seasonal variations, with the maximum in summer. Water use efficiency also displayed seasonal variation, with the maximum in autumn. Under no stress, Tr obviously changed with tree ages, with the order of 1 year-old > 3 year-old > 7 year-old. The rate of Tr/Pn in spring, summer and autumn was higher than that of other deciduous broad-leaved trees in the same region, especially in summer. The high Tr/Pn ratio means a high water consumption, which is beneficial to water loss of poplar I-69/55. In shoal sites, the temperature of leaf surface in summer and autumn is the most important factor that affects the transpiration rate of poplar I-69/55, suggesting that decreasing the temperature of leaf suface is beneficial to increase the transpiration rate. During the two days after flooding, the temperature of leaf surface is still the important factor that affects transpiration rate. PMID- 11767669 TI - [Soil moisture dynamics in forest land and wasteland of Loess Plateau]. AB - The dynamics of soil moisture stored in a wasteland and in a forest land in the sub-humid climate region of the Loess Plateau was measured with neutron moisture meter for three successive years. Within the depth of 0-320 cm, the increment of soil water in the test 3 years was respectively -165.7 mm, -15.2 mm and -115.2 mm at the upper and lower position on north slopes and the lower position on south slope of the wasteland. Soil water increased by 17.2 mm at the upper position on north slope of the Chinese pine forest land, after > 380 mm water was consumed yearly by tree transpiration. It is suggested that forest land is essentially different from wasteland in soil water income/expense. The necessity of conducting the approaches for gaining available water of forest land was put forward. PMID- 11767670 TI - [Numerical simulation on maize growth in a regular windbreak system in Huanghuaihai Plain]. AB - The modified production ecological model SUCROS was used to simulate the growth process of summer corn with the protection of windbreaks in Huanghuaihai Plain, and the simulated result was compared with the field monitoring data. The effects of various physiological and ecological factors that affect the growth of the summer corn were analyzed. The modified SUCROS could simulate the growth process successfully. The leaf area index and organ biomass simulated by the model could be fairly consistent with the monitoring data when the effects of insect and disease pests and weeds were considered simultaneously. As compared with the simulated data in the monoculture field, the corn yield in the windbreak system was about 6.8% higher due to the improved microclimate. Based on the simulation of the relationships between sowing density, sowing date and seed production, the density standard for high yield in the region was 6.75-7.50 plants.m-2, even high as 9.00 plants.m-2 in the fields with sufficient soil nutrients and water supply. It is suggested that the optimal sowing period is from May 21 to June 5. Through simulating the influence of "cool summer" on the growth of summer corn in southern Huanghuaihai Plain, it was found that the growth period of corn would extend 3 to 4 days if the average air temperature during the growing period lowered by one degree. The "less radiation" and correspondent "lower temperature" were the direct reasons of yield reduction in "cool summer". PMID- 11767671 TI - [Mechanism of nutrient preservation and supply by soil and its regulation. IV. Fertility regulation and improvement of brown earth type vegetable garden soil and their essence]. AB - Pot experiment studies on the fertility regulation and improvement of fertile and infertile brown earth type vegetable garden soils and their functionary essence show that under conditions of taking different soil fertility improvement measures, the nutrient contents in fertile and infertile soils were not always higher than the controls, but the aggregation densities of soil microaggregates were increased, and the proportion of different microaggregates was more rational. There was no significant relationship between soil productivity and soil microaggregates proportion. It is proved that the essence of soil fertility improvement consists in the ultimate change of the preservation and supply capacities of soil nutrients, and the proportion of soil microaggregates could be an integrative index to evaluate the level of soil fertility and the efficiency of soil improvement. PMID- 11767672 TI - [Coupling effect of water and fertilizers on spring wheat yield in semi-arid area of western Liaoning Province]. AB - With optimum saturation design, a field experiment was conducted to study the coupling effect of water and fertilizers on spring wheat yield in semiarid area of western Liaoning Province. Regression model shows that water was the most important factor affecting spring wheat yield. Under natural raining and when the upper and the lower limit of irrigation was 360 mm and 45 mm, respectively, N was the most sensitive factor, water was the second, and P was the third. The effects of N, P and water on yield were statistically significant, and met the law of diminishing return. The most economic matching pattern of N, P and water was N 186 kg.hm-2, P 63 kg.hm-2, and water 300 mm. Properly increasing phosphorus fertilizer at the lack of water could strengthen the drought-resistance of spring wheat. PMID- 11767673 TI - [Effect of interaction between water and fertilizer on wheat and maize semiarid region of western Liaoning]. AB - Using 312-D optimum design and quadratic general rotation design, the effect of interaction between water and fertilizer on wheat and maize yields was studied in semiarid region of western Liaoning Province. Reasonable combination of applying N and P fertilizers, irrigation, and mulching corn straws could increase crop yield remarkably, otherwise, it could not only increase cost, but also result in output reduction due to increasing crop stress to water or nutrients. Based on the results of the trials, the effects of the productive factors on crop yield were analyzed. The optimum economical combination of water and fertilizers fitting for local agriculture was put forward, i.e., water 120.2 mm, N 58.5 kg.hm 2, and P2O5 123.0 kg.hm-2 for wheat, and water 173.3 mm, N 256.5 kg.hm-2, P2O5 85.5 kg.hm-2, and straw mulching 8509.5 kg.hm-2 for maize. PMID- 11767674 TI - [Rhizosphere effect of nutrients in different maize soils with different fertility levels]. AB - Maize plants and soil samples were collected from Jilin Province to study the nutrient dynamics in soil-maize plant rhizosphere and their relationship with plant uptake. The results showed that NH4(+)-N and NO3(-)-N were accumulated in rhizospheric soil, and mainly controlled by the application of chemical fertilizers. Soil available P was depleted in high fertility fields, especially in high seedling density, while accumulated in low fertility fields. Soil available K was accumulated in rhizospheric soil, and its accumulation rate was higher in high fertility than in low fertility fields. The nutrient absorption amount was N approximately K > P for maize plant shoots and roots, but was N > K > P for seeds. The contribution rate of chemical fertilizers to maize yield was only 1/5-1/3 in Jilin Province, and the rest was contributed by the application of organic manure, such as chicken feces or cow feces, and by the mineralization of soil organic matter. PMID- 11767675 TI - [Effect of long-term no-tillage and application of organic manure on some properties of soil fertility in rice/wheat rotation]. AB - A field experiment from June 1983 to October 1997 was conducted to study the effect of long-term no-tillage and application of manure on soil fertility properties. The results showed that the contents of soil organic C, total N and available N in the treatment of fourteen consecutive year no-tillage were all significantly higher in 0-5 cm soil layer, while, lower in 5-10 and 10-20 cm layers than in conventional tillage. The content of water stable aggregate in 0 20 cm layer was increased in no-tillage in that the soil structure was less destroyed. Based on various soil fertility properties, the contribution order of different fertilization treatments to soil fertility was as follows: pig manure > straw > green manure > chemical fertilizer > no fertilizer. PMID- 11767676 TI - [Phosphate adsorption characteristics of paddy soils derived from main parent materials in Guangdong Province]. AB - Isothermal adsorption experiment of phosphate on paddy soils drived from five different parent materials in Guangdong Province was carried out. The result showed that the adsorption data of different test soils could be simulated well by Langmuir, Freundlich and Temkin equations, and the Langmuir equation fitted the data best (correlation coefficient r: 0.995-0.999..). As a value of phosphate adsorption characteristics, the product of phosphate adsorption maximum (Xm)and sorption intensity factor(K) calculated by Langmuir equation could be a comprehensive index to characterize the potential phosphate adsorption by paddy soil, and could indicate the order of applying phosphate. The result also indicated that there exists two types of sorption region on the soils tested. PMID- 11767677 TI - [Spatial variability of soil nutrients based on geostatistics combined with GIS- a case study in Zunghua City of Hebei Province]. AB - Geostatistics combined with GIS was applied to analyze the spatial variability of soil nutrients in topsoil (0-20 cm) in Zunghua City of Hebei Province. GIS can integrate attribute data with geographical data of system variables, which makes the application of geostatistics technique for large spatial scale more convenient. Soil nutrient data in this study included available N (alkaline hydrolyzing nitrogen), total N, available K, available P and organic matter. The results showed that the semivariograms of soil nutrients were best described by spherical model, except for that of available K, which was best fitted by complex structure of exponential model and linear with sill model. The spatial variability of available K was mainly produced by structural factor, while that of available N, total N, available P and organic matter was primarily caused by random factor. However, their spatial heterogeneity degree was different: the degree of total N and organic matter was higher, and that of available P and available N was lower. The results also indicated that the spatial correlation of the five tested soil nutrients at this large scale was moderately dependent. The ranges of available N and available P were almost same, which were 5 km and 5.5 km, respectively. The range of total N was up to 18 km, and that of organic matter was 8.5 km. For available K, the spatial variability scale primarily expressed exponential model between 0-3.5 km, but linear with sill model between 3.5-25.5 km. In addition, five soil nutrients exhibited different isotropic ranges. Available N and available P were isotropic through the whole research range (0-28 km). The isotropic range of available K was 0-8 km, and that of total N and organic matter was 0-10 km. PMID- 11767678 TI - [Environment capacity of eco-tourism resort]. AB - The results of quantitative analysis on the amount of tourist, service environment capacity, eco-environment capacity, and their relations in Five finger Mountain eco-tourism resort indicate that the amount of tourist in common situation and in its extreme was 1918 and 2301 visitor-hour per day, and the service-environment capacity and eco-environment capacity were 6000 and 2400 visitor-hour per day, respectively. The eco-environment capacity was smaller than its service-environment capacity, and would become the first limiting factor to the increase of tourist amount, which was mainly due to the ecological fragility of resort, the lower resistance of biological communities to the disturbance, and the slower speed of ecosystem restoration after its being destroyed. PMID- 11767679 TI - [Landscape structure of Longhua area in Shenzhen City during fast urbanization process--structure and heterogeneity analysis of urban construction area]. AB - Remotely sensed mapping information of multi-period of time and methods of landscape pattern analysis were used to study the structure and spatial distribution characteristics of two types of land use, built-up areas and new developing areas, during the fast urbanization process in Longhua area, Shenzhen City. The results indicated that from 1988 to 1996, the patch number and average size in the two types of land use increased significantly, but the fragmentation degree decreased. The increase of constructed land use could be divided into two patterns, continued expanding of big residential patches and continuous appearing of new isolated small patches, and most of the new developing area was constructed from 1990 to 1994. Under the impacts of topography and traffic, the built-up areas showed macroscopic spatial distribution with decreasing lacunarity values. Distribution difference of constructed patches was very obvious in small and moderate scales. The new developing patches, affected by the conditions as the built-up areas, were also characteristic of macroscopic heterogeneity, but the expression scale of heterogeneity was larger than the built-up areas. The fast expanding of the constructed land use produced some very negative ecological problems, which should urgently be resolved by adjusting the land use polices. PMID- 11767680 TI - [Land use dynamic monitoring supported by remote sensing and GIS--a case study in Kenli County of Yellow River delta]. AB - By remote sensing both visual interpretation and computer aided classification, the land use information of Kenli County of Yellow River delta in 1981, 1991 and 1995 was compared and analyzed. The unifying land use dynamic monitoring classification system was made, and the methods of land use dynamic monitoring both on land use type areas and on their spatial distribution were proposed. The changes of land use type areas of Kenli County were analyzed, and the spatial dynamics of land use types from 1981 to 1995 was analyzed under GIS support. In addition, the land use changes of outdoor monitoring plots were analyzed, and the basic patterns of land use dynamics of Kenli County were proposed. PMID- 11767681 TI - [NO emission from winter wheat fields of rice-wheat rotation ecosystem in southeast China]. AB - Measurements of NO emission from the winter wheat field of rice-wheat rotation ecosystem in southeast China during the whole period of wheat growth show that a higher NO emission was observed in spring than in autumn, and almost no emission in winter could be detected. Temperature was the most important factor determining the seasonal variation pattern of NO emission. Although the N fertilization might enlarge NO emission by a factor of 5-7, it could not modify the seasonal variation pattern. During the period of relatively weak plant activity, the diurnal variation pattern, with the maximum emission at 9:00-14:00, was determined by temperature. When plants luxuriated, however, the competition of NH4+ by plant uptake and by microbial nitrification led to a night-peak variation pattern, in which, the maximum diurnal emission usually occurred during 18:00 and 4:00 of next day, and the minimum at 8:00-16:00. PMID- 11767682 TI - [Primary identification of organic compounds in soybean rhizospheric soil on continuous and alternate cropping and their allelopathy on soybean seed germination]. AB - Organic compounds extracted with ethanol (OCEWE) from soybean rhizospheic soil on continuous and alternate cropping at pod-string were identified by gas chromatography-mass spectrometry (GC-MS). The results showed the compounds mainly include organic acids, alcohol, acetone, aldehyde, naphthalene phenyl and furan hydrocarbon, many of which were reported as allelochemcals. Under this experiment condition, OCEWE did not show any allelopathy on soybean seed germination and radicle growth, which might be related with their critical toxicity concentrations. In addition, the relationship between allelopathy and barrier on soybean continuous and alternate cropping was also discussed. PMID- 11767683 TI - [Physioecological characteristics of four dominant plant species in Kerqin sandy land]. AB - The photosynthetic and water physioecological characteristics of four dominant species, Caragana microphylla, Artemisia halodendron, Artemisia frigida and Populus spp(a hybrid), in Kerqin sandy land were compared. The photosynthesis rates of C. microphylla, A. halodendron, and Populus spp. reached highest at 6:00, rapidly fall at 8:00, remained at low level from 8:00 to 16:00, then rose slowly after 16:00. The photosynthesis rate of A. frigida was comparatively low at 6:00, so the range of declining speed was small. Diurnal photosynthesis rate of Artemisia frigida decreased at 6:00-8:00, C. microphylla at 8:00-10:00, Populus spp and. A. halodendron at 6:00-10:00, and was controlled by stomatal limitation; in rest time, it was controlled by non-stomatal limitation. The four species also adapted different ways to resist drought stress. C. microphylla and A. frigida resisted drought stress through their low transpiration, low water potential and high ratio of bound water to free water(BW/FW); Populus spp. resisted drought stress through its rapid fall of stomatal conductivity to reduce its transpiration in spite of its high water potential and high BW/FW, while A. halodendron resisted drought stress weakly because of its high transpiration, high water consumption and low water use efficiency. PMID- 11767684 TI - [Energy allocation to growth and reproduction in Leymus chinensis population]. AB - Studies on energy allocation to growth and reproduction in Leymus chinensis population show that the average calorific value of modulus was decreased in the order of ear > leaf sheath of vegetative shoot > leaf sheath of sexual shoot > leaf of vegetative shoot > stem of vegetative shoot > stem of sexual shoot > leaf of sexual shoot > litter, and the energy allocation rate of vegetative and reproductive growth was in the order of vegetative shoot > rhizome > litter > sexual shoot. The dynamics of energy allocation rate of modulus was different with seasons. Among all reproductive stem modulus, the rate of energy allocation to stem and leaf sheath of sexual shoot was higher than that to ear and leaves. PMID- 11767685 TI - [Effect of AM fungi on water and nutrition status of corn plants under salt stress]. AB - Under NaCl stress, the dry matter production of corn plants inoculated with or without arbuscular mycorrhizal (AM) fungus (Glomus mosseae) was decreased, but the decrement for non-mycorrhizal plants was 10% higher than that for mycorrhizal ones. Under salt stress condition, the dry weights of root system and aboveground part of mycorrhizal corn and its leaf water potential were higher than those of non-mycorrhizal corn, while the proline content of mycorrhizal corn was less than that of non-mycorrhizal corn. The contribution of hypha to P uptake of plants decreased from 45.3% to 42.6%, while the effect of AM fungi on plant growth increased from 30.9% to 63.5% under salt stress condition. The above-mentioned results indicated that the mechanism that AM fungi enhance the salt-resistance of corn is related with the improvements of water and P nutrition conditions. Meanwhile, it was found whether under salt stress or not, the ratio of P accumulation of root system to aboveground part of mycorrhizal corn was higher than that of non-mycorrhizal corn, indicating that the infection of AM fungi changed the P distribution pattern in plant bodies, which is beneficial to increase the salt-resistance of plants. PMID- 11767686 TI - [Epizootic dynamics of Spodoptera litura nuclear polyhedrosi virus]. AB - Through investigation of tracking infected Spodoptera litura larvae, the epizootic dynamics of S. litura nuclear polyhedrosis virus(SlNPV) in field was studied with different dosages of SlNPV. The results showed that in the range of virus dosages (3.1 x 10(5)-3.1 x 10(8) PIBs.ml-1), the initial infection syndrome was observed after 4 days of treatment, and peaked in 5-7 days. The larvae mortality occurred after 5-6 days of treatment, and peaked in 6-8 days. The prevalence peak of host was basically coincident to the incidence peak. The distribution of diseased incidence of hosts and disease death time could be quite simulated by time-dosage-mortality model(TDM). Hosmer-Lemoshow test showed that the predicted values well fitted with observed data, and t-test indicated the parameters of the model reached significant level(P < 0.0001). The distribution of diseased prevalence was simulated by Holliday model, the regression of function was significant by F-test, and the parameters of the model reached or approached significant level(p < 0.005). TDM model could be used to predict the daily incidence, prevalence, disease death rate of present generation population of host pest. PMID- 11767687 TI - [Flight capacity and facultative migration of cotton bollworm]. AB - The flight capacity of moth cotton bollworm was studied by hanging flight installation. According to the flight rhythm and time, the individuals of population could be differentiated into long, medium, and short flight type. Laboratory stuies on the effect of temperature and food on pre-reproductive period, fecundity and life-span showed that the pre-reproductive period was only 2.13 +/- 0.67 days under 28 degrees C, and food or temperature had no significant effect on pre-reproductive period. The physiological period fitting for migration was quite short, only 1-2 nights. The population sources in Fengxian county, Jiangsu province and Chaoyang city, Liaoning province were studied by analysis of the dissecting of females ovary and the patterns of moth occurrence sequentially. The result indicated that the 2nd and 3rd generation moths in Chaoyang all or partly immigrated from other places, while in Fengxian, there was no migration. The flight capacity and reproductive characteristics of moth cotton bollworm were compared with other migratory or un-migratory species. The facultative migration and potential for migration of this species were discussed. PMID- 11767688 TI - [Hunger tolerance of Microvelia horvathi hibernating generation]. AB - The experimental results showed that the hunger tolerance (HT) of different wing forms Microvelia horvathi adults had significant difference at 14-32 degrees C, and decreased with increasing temperature, which was 32.10 and 29.58 days at 14 degrees C, and 9.46 and 7.82 days at 32 degrees C, respectively for apterous and pterygote adults. The HT of apterous adults was higher than that of pterygote ones, and females was higher than males with the same wing form. The lower the temperature, the bigger the difference. The HT of M. horvathi adults differed obviously with densities. 1 female 1 male per bottle had a higher HT than 5 females 5 males per bottle and 10 females 10 males per bottle, while no difference was found between two latter densities. The HT of the 1st instar nymphs of M. horvathi had an obvious difference at different temperatures, which was significantly higher at 14 and 20 degrees C than at 26 and 32 degrees C. PMID- 11767689 TI - [Niche breadth of Gymnosporangium haraeanum]. AB - The resistant difference among different main pear cultivars in Anhui Province to pear rust caused by Gymnosporangium haraeanum was significant. According to disease index and diseased leaves of susceptible cultivars, the niche breadths of hosts were 0.7555 and 0.7951, respectively. The niche breadths of horizontal and vertical space of each cultivar were approximate to 1. The result shows that the infection of G. haraeanum was a random distribution. PMID- 11767690 TI - [Effect of temperature and body weight on carbon budget of Penaeus chinensis]. AB - The carbon budget of Penaeus chinensis feeding on polychaet worm(Neanthes japonica) was determined at various levels of temperature (20 degrees C, 25 degrees C, 30 degrees C) and body weights(0.271 +/- 0.041 g, 3.509 +/- 0.301 g, 11.062 +/- 1.027 g) from May to September, 1996. The results show that the carbon consumption was significantly affected by water temperature and body weight, which significantly increased with increasing temperature and decreasing body weight. The average carbon consumptions at 20 degrees C, 25 degrees C and 30 degrees C were 12.41, 19.12 and 26.08 mg.g-1.d-1, and those for 3 body weights were 36.06, 12.17 and 9.38 mg.g-1.d-1, respectively. The intake carbon allocation was not significantly affected by body weight, but significantly affected by water temperature. The proportions of carbon allocated to growth, fecal, exuviation and metabolism at three different temperatures were 31.23%, 4.28%, 7.94%, 56.45%; 26.83%, 2.92%, 6.69%, 65.79%; 16.86%, 2.38%, 5.99%, 74.76%, respectively. PMID- 11767691 TI - [Effect of temperature on energy budget of Taiwanese red tilapia hybrid (Oreochromis niloticus x O. mossambicus)]. AB - The energy budget of Taiwanese red tilapia hybrid (Oreochromis niloticus x O. massambicus) with a body weight of 25.33-26.23 g was measured at salinity 14 and at water temperature 22, 28 and 34 degrees C in July-August 1996. The results showed that its specific growth rate, conversion efficiency and maximum food consumption were significantly affected by temperature, and reached peaks of 1.79, 60.01% and 2.59% B.W.d-1 at 28 degrees C. The effect of temperature on the absorption efficiency was not significant, with an average absorption efficiency 64.58%. The effect of temperature on the proportions of food energy allocated to each component of the energy budget was significant. The ratio of growth energy was the highest(26.4%) at temperature 28 degrees C, and that of metabolism energy was 37.23%. PMID- 11767692 TI - [Interaction of Cu and Pb in accumulation process by fish]. AB - With synthetic water, the accumulation of co-existed Ca and Pb by Paracheirodon innesvi and of Pb by Cu-tamed P. innesvi was studied. The result showed that under both conditions, there existed a significant synergistic effect on the accumulation of Cu and Pb by the fish. PMID- 11767693 TI - [A primary study on distribution and binding forms of arsenic in polluted crop seeds]. AB - The distribution, binding form and processing removal of arsenic in rice and wheat seeds were studied. The result shows that the distribution of arsenic in seed parts was uneven, as concentration in rice seed was embryo > seed capsule > chaff > endosperm, and that in wheat seed was embryo > seed capsule > endosperm. Arsenic was mainly accumulated in endosperm, and mainly in the form of protein binding. With the removal of chaff, coarse rice bran and fine rice bran in the processing, the content of arsenic decreased by 16.51%, 12.41% and 10.26%, respectively. Similarly, with the removal of coarse wheat bran and fine wheat bran, it decreased by 22.0% and 45.6%, respectively. PMID- 11767694 TI - [A primary study on chemical bound forms of copper and zinc in wheat and rape]. AB - Sequential extraction method was used to analyze and distinguish various chemical bound forms of copper and zinc in rape and wheat. The results show that in these two crops, copper was mainly in the form of wate soluble and ethanol soluble, which can be easily transferred in crops. The total content of various chemical bound forms of copper was higher in aboveground part than in underground part, and their content was decreased in the order of water soluble form (W.S. form) > residual form (Re. form) > ethanol soluble form(Eth. S. form) > acid soluble form (A.S. form). Zinc was mainly in the form of acid soluble, which is hard to be transferred in crops. The total content of various chemical bound forms of zinc was lower in aboveground part than in roots, and their content was decreased in the order of A.S. form > Re. form > W.S. form > Eth. S. form. In comparing with copper, a large amount of zinc was enriched in seeds and pods of rape. PMID- 11767695 TI - [Molecular markers and their application in plant population research]. AB - This review surveys kinds of markers such as allozyme, AFLP, RAPD, SSR, RFLP and their application in molecular ecology of plant populations. The advantages and disadvantages of these molecular markers in plant population research are discussed based on the comparison of the methods and the experience in research work. It is considered emphatically that the adoption of the molecular markers is dependent on the various research purposes and different quality and quantity of the molecular information are acquired from various molecular marker methods. PMID- 11767696 TI - [Consideration for ecological planning in mining areas]. AB - On the basis of summarizing the status and trend of domestic and overseas ecological planning research, the necessity and significance of ecological planning research in mining areas were analyzed and its characteristics, research objectives, contents and methods were discussed. It is pointed out that establishing the theory and methodology of ecological planning in mining area is not only the requirement of their sustainable development, but also the requirement of active participation and cooperation of the researchers from different disciplines. PMID- 11767698 TI - [The window parascapular free flap for the treatment of severe facial scar contracture]. AB - OBJECTIVE: To present the clinical application of the window parascapular free flap. METHOD: The window parascapular free flap was used in 6 cases of serious facial burn scar contracture. The age of the patients ranged from 5 to 17 years. Based on circumflex scapular vessels, small windows were made on the flap for the palpebral fissure, the oral fissure, the nostrils or the external auditory meatus. The flap size ranged from 15 cm x 8 cm to 17 cm x 17 cm. All the free flaps were successful. RESULTS: With the survival of the free flap, the nose, the lids, the lips, etc. were reconstructed at the same time and obtained good appearance. CONCLUSION: For repair of serious facial burn scar contracture, the window parascapular free flap was successfully used to reconstruct the eye, the mouth, the nose and the ear. The method is safe and reliable because the blood supply of the scapular free flap was not affected by the opening. PMID- 11767697 TI - [The tensor fascia lata racket shape myocutaneous island flap]. AB - OBJECTIVE: To provide a racket shape tensor fascia lata myocutaneous island flap according to the anatomical form and blood supply of the tensor fascia lata. METHODS: Four tensor fascia lata racket shape myocutaneous island flaps were used in four patients clinically. All 4 flaps were for repairing abdominal defect. RESULTS: Three of the four flaps survived without complication. In one of the four flaps, skin necrosis at the distal tip was noted and needed additional skin graft. CONCLUSIONS: The tensor fascia lata racket shape myocutaneous island flap is a convenient island flap. The island flap designed like racket shape has two benefits than the conventional rectangular island flap: 1. The narrow proximal part of the flap is like a extended pedicle, which makes the broad distal part of the flap can easily be transposed to the recipient site. 2. The donor defect of the narrow proximal part can be closed directly, which lessens the size of skin graft for the donor defect. The cause of skin necrosis at the distal tip of one flap is mainly due to that the length of the flap exceeds the distal end of the middle one third of the lateral thigh. PMID- 11767699 TI - [Clinical application of the reversed digital arteial island flap with digital wein and digital dorsal nerve anastomosis]. AB - OBJECTIVE: To introduce clinical application of the reversed digital arteial island flap with digital wein and digital dorsal nerve anastomosis to repair digital soft tissue defect. METHODS: Since 1999, 10 cases involving 14 digital defects associated with exposure of bone or tendon were treated by using the reversed digital arterial island flap with digital vein and digital dorsal cutaneous nerves anastomosis. RESULTS: All the flaps were 100% survived and the result is satisfactory. CONCLUSIONS: The reversed digital arterial island flap with anastomosing the digital vein and dorsa digita nerve is a safe, and simple technique, which can maintain the finger's normal appearance and reduce the incidence of venous crisis and improve the survival rate of the flap. PMID- 11767700 TI - [Eyelid reconstruction with a reversal flow axial preauricular island flap based on the supraorbital artery]. AB - OBJECTIVE: In order to find an ideal flap to reconstruct the eyelid defect, we have explored the possibilities to reconstruct eyelid with a reversal flow axial preauricular island flap based on the supraorbital artery. METHODS: According to Chen's theory on "reversal flow axial flap", we designed and applied the reversal flow axial preauricular island flap based on the supraorbital artery, which could nourish the flap by anastomotic branches between the supraorbital artery and the frontal branch of the superficial temporal artery. RESULTS: We have successfully reconstructed 7 cases of eyelid defect with this method since 1997. The size of the flaps ranged from 4.0 cm x 2.4 cm to 2.0 cm x 1.8 cm and good result were revealed with 1-2 years follow up. CONCLUSIONS: The flap has a stable and reliable blood supplying. It is an ideal flap to reconstruct the eyelid defect for texture and color similarity of the eyelid and preauricular skin. PMID- 11767701 TI - [Applied anatomic study of the pudendal-thigh flap and establishment of flap model]. AB - OBJECTIVE: To investigate the anatomic base of the pudendal-thigh flap and establish flap model. METHODS: Skin dissection of pudendal-thigh regions was performed on 10 cadavers (20 sides). All afferent and efferent vessels were measured and recorded. RESULTS: There exist multiple blood supplies of pudendal thigh flap. Anterior cutaneous branches of obturator artery spread out on middle portion of flap. Piercing site of it is (3.0 +/- 0.5) cm apart from middle line of perineum, (1.7 +/- 0.4) cm from anterior margin of vaginal introitus, (0.6 +/- 0.2) cm from outer fringe of lower pubic rami and (0.8 +/- 0.1) mm in diameter. Posterior labial arteries mainly supply the major labia and constantly anastomose with superficial external pudendal arteries in direct vascular anastomosis in subcutis of major labia. The main stems send out 2-3 lateral branches of posterior labial arteries which distribute to posterior portion of the pudendal thigh flap. CONCLUSION: The major vessels of pudendal-thigh flaps used to form a neovagina are lateral branches of posterior labial arteries and not the main stem itself. Flaps pedicled on the anterior cutaneous branches of obturator arteries may be elevated to repair rectovaginal fistula or small skin defects of perineum and not suited to reconstruct a neovagina as its piercing point of blood vessels is much higher and the location of pedicle is more fixed. PMID- 11767702 TI - [Establishment and application of experimental animal model for hypertrophic scar]. AB - OBJECTIVE: To establish a real animal model for hypertrophic scar. METHODS: 388 wounds on the ears of 47 rabbits were created including rounds 6 mm in diamiter on ventrol or dorsal side and 1.5 cm x 4.5 cm rectangular wounds. Histological and histochemical analyses, in situ hybridization and cell apoptosis were tested. RESULTS: 70 percent of the wounds can from excess dermal scarring which is similar to human hypertrophic scar. The hight of excess dermal scarring is as 3-4 times high as original ventol skin. The excess scarring can last 150 days at the most. while 80 percent appears on rectangular wounds and it lasts more than 262 days. Large amount of fibroblasts, nodular and spiral structures exist in excessive dermal scarring. Local injection of TGF-beta 1 and IFN-r can promote and inhibit the formation of excessive dermal scarring respectively. SDS-PAGE shows that type III collagen content increased in excessive dermal scarring. In situ hybridization shows long-lasting expression of type I and III precollagen mRNA in excessive dermal scarrint. TGF-beta 1 mRNA also cope with that of precollagen. Fibroblast apoptosis in excessive dermal scarring of this model indicate that fibroblast apoptosis plays an important role in the process of occurrance, development of abnormal scar. CONCLUSION: After wounding, rabbit ears can produce excessive dermal scarring which is similar to human hypertrophic scar. This can be used as an experimental model for the study of cicatrix. PMID- 11767703 TI - [Study on apoptosis of fibroblasts from abnormal scars in media containing low level of serum and interleukin 1 beta]. AB - OBJECTIVE: To investigate the effects of low serum and interleukin 1 beta on inducing apoptosis of fibroblasts from abnormal scars and normal skins. METHODS: 6 samples from keloid, hypertrophic scar and normal skin were collected respectively. Apoptosis of different fibroblasts in media containing low level of serum and interleukin 1 beta were studied by detecting Bax and Bcl-2 protein expressions and specific DNA ladder by means of cell culture, immunohistochemistry and agrose electrophoresis. RESULTS: 1. In low level of serum, hardly occurs apoptosis of fibroblasts from keloids in correspondence with no changes of the radio of Bax/Bcl-2 proteins, and apoptosis of fibroblasts from normal skins occurs in correspondence with increasing of the radio of Bax/Bcl-2 proteins, whereas, slightly occurs apoptosis of fibroblasts from hypertrophic scars in correspondence with no change of the radio of Bax/Bcl-2 proteins. 2. In media containing interleukin 1 beta apoptosis of all three kinds of fibroblasts occurs, whereas, apoptosis of fibroblasts from keloids and hypertrophic scars takes place more seriously than that from normal skins in correspondence with increasing of the Bax/Bcl-2 radio of fibroblasts from keloids, decreasing of the Bax/Bcl-2 radio of ones from normal skins and no change of the Bax/Bcl-2 radio of ones from hypertrophic scars. CONCLUSION: Characters of different fibroblasts are different. PMID- 11767704 TI - [Immunological regulations of dendritic cell in abnormal scarring tissue]. AB - OBJECTIVE: To investigate the relationship between dendritic cell(DC) and pathogenesis of abnormal scar. METHODS: The content of HLA-DR and CD1a molecules of DC, in 6 samples of hypertrophic scar (HS), keloid (K) and normal skin, were determined with the stain of avidin-biotin-peroxidase complex method (ABC). The effect of Triamcinolone Acetonide was evaluated with the measurement of the HLA DR and CD1a molecules of DC in the epidermis of the HS. RESULTS: 1. The amounts of HLA-DR molecules of the positive DC were 806.67 +/- 101.72 and 870.00 +/- 134.24 in the HS and the K respectively, significantly higher than the controlled normal skin (510.01 +/- 45.17, P < 0.05). HLA-DR molecules showed an abnormal expression in the Kerationcytes and fibroblasts. 2. The amounts of CD1a molecules of the positive DC were 700.00 +/- 97.23 and 780.00 +/- 104.47 in the HS and the K respectively, significantly higher than the controlled normal skin (521.24 +/- 57.87)(P < 0.05). 3. The amounts of the HLA-DR molecules positive DC, in the positive kerationcytes and fibroblasts of hypertrophic scar, treated by Triamcinolone Acetonide, were 476.67 +/- 70.02 and 447.76 +/- 90.03 (P < 0.05) for 3 days and 7 days treatment respectively, significantly lower than the control. The amounts of CD1a molecules positive DC in the epidermis of hypertrophic scar with the injection of Triamcinolone Acetonide were significantly lower in 3 days and 7 days treatment (456.36 +/- 82.88 and 397.18 +/- 99.36, P < 0.05). CONCLUSION: 1. The results, with the high expression of HLA DR and CD1a molecules, indicate that the HS and the K may have strong immune reactions. 2. Triamcinolone Acetonide may decrease the immune reactions of the HS, through the inhibition of the expressions of HLA-DR and CD1a molecules in the dendritric cell. PMID- 11767705 TI - [A study on the relationship between intake hole of the liposuction-tube and the amount of liposuction]. AB - OBJECTIVE: To investigate the relationship between the liposuction-tube's intake hole and the amount of liposuction. METHODS: 4 groups were divided, according to the liposuction-tube intake hole's shape, area and the tube installed electrotome or not, to suck the exsomatized fat, then made a quantitative analysis. RESULTS: It can suck more fat by using a tube with a double-two-toothed hole than with two toothed hole or with diamond hole. We can get the largest amount of fat when the hole's area is the double of the tube's area. It's more effective when the tube installed with electrotome than without electrotome. CONCLUSION: It's by far the most effective in liposuction when the intake hole's area is the double of the tube's area, the shape is a polygona with cutting edge, and also the tube is installed a high-frequency electrotome. PMID- 11767706 TI - [Postliposuction histologic alteration of adipose tissue in mini-pig models]. AB - OBJECTIVE: To study the postliposuction histologic alterations of adipose tissue in Mini-pigs. METHODS: Five Wuzhishan adult Mini-pigs were suctioned with syringe assisted liposuction using a suction needle of 2 mm in diameter. The subcutaneous adipose tissues on both operated and controlled non-operated areas were collected from one week to eight months after operation and all samples were measured and observed macroscopically and microscopically. RESULTS: The thickness of subcutaneous adipose tissues at the operated sites is thinner than the controlled sites. There was no significant difference in adipocyte morphology between the two kinds of samples. The structure of fat tissue recovered normally during 6-8 months after liposuction. CONCLUSION: Liposuction is an effective operation to eliminate the subcutaneous adipose tissue and the structure of subcutaneous adipose tissue is completely normal in 6-8 months after the operation. PMID- 11767707 TI - [Experimental comparison of the adipocytal injuries harvested by three surgical methods]. AB - OBJECTIVE: To evaluate the degree of the injuries on the fat cells harvested by cutting, syringe aspiration and pipe suction techniques. METHODS: Fat tissue was removed from lower abdomen by cutting, syringe aspiration and pipe suction. The excised adipose tissue was cut into 3 mm diameter fat particles, whereas the adipose tissue from syringe aspiration group was taken by the syringe suction technique with No. 22 needle and in the pipe suction group the adipose tissue from the suction tube with 8 mm in diameter. Each sample was fixed in 10% buffered formalin and stained with hematoxylin technique and wilder's silver technique. The fat cells were evaluated under microscope. RESULTS: The percentage of the injured fat cells was (8.6 +/- 1.8)% in cutting technique, (15.7 +/- 2.4)% in syringe aspiration and (76.4 +/- 8.7)% in pipe suction respectively. They had significant differences between each other. CONCLUSIONS: Among the three methods, the degree of the injuries on the fat cells was mostly serious in the way of pipe suction technique while minimal in the way by cutting. PMID- 11767708 TI - [Correction of nasal deformity in unilateral cleft lip of adult cases]. AB - OBJECTIVE: Nasal deformities are very common in unilateral cleft lip cases. They are morphology of alar collapse, nasal floor depression and deviation of the septum. METHODS: Our operation procedure includes correction and replacement of the septum to the middle position, mobilization and suspension of the displaced alar cartilage and use of a "C" flap, nasal sill flap or a flap of the lip scar tissue to increase the length of columella on the cleft side. An implant or autograft of suitable size is placed, if necessary, in the nasal bridge or/and the nasal floor. RESULTS: Postoperative follow-up for 1-12 months showed that the results are satisfactory. CONCLUSIONS: Correction of septum deformity, and increase of the length of the columella on the cleft side are important. An extensive mobilization and reposition of the alar cartilage must be done for obtaining a symmetric nasal projection. If necessary, a fine implant or self tissue is placed in the nasal bridge and nasal floor, which would make the result much better. PMID- 11767709 TI - [Use of autogenous cranial bone grafts for orbital floor reconstruction]. AB - OBJECTIVE: To evaluate the effects of autogenous calvarial bone grafts on treatment of the patients with defect of orbital floor from facial trauma. METHODS: During a 5-year period from April 1994 to April 1999, 34 patients ranging in age from 16 to 68 years (twenty males and fourteen females), who presented with orbital floor defects associated with other facial fractures were reconstructed by autogenous calvarial bone grafts. The surgical approach to the orbital floor involved a transconjunctival incision in 31 patients and a subciliary incision in 3 patients. After the orbital floor exploration, the bone graft was harvested through the coronal incision in 29 patients and the parietotemporal region incision in 5 patients. The bone graft was then fashioned to the appropriate size and configuration and fixed to the stable bone of the orbital floor with microplates or screws. RESULTS: The surgical incisions healed well with a minimal scar. There were no infection, extrusion or other complications associated with autogenous calvarial bone graft. There were no cases of optic neuropathy, diplopia and enophthalmos. There was no morbidity in donor sites. One patient had slight ectropion, which lasted three months and became inconspicuous in six months. 8 cases with hypoesthesia of the infraorbital region returned the sensory function within 6 months. 6 patients with enophthalmos were partly corrected. The follow-up period ranged from 6 months to 5 years. CONCLUSION: The orbital floor defects should be managed by early exploration to avoid later complications. The sequel, such as enophthalmos and dystopia or diplopia are much more difficult to correct after bony union. A vast array of autogenous and alloplastic materials have been used to reconstruct the defect of orbital floor. Autogenous bone graft reduces the risk of infection and extrusion. Cranial bone graft produces less donor site morbidity compared with other sites, non-visible scar as the incision is placed within the hair-bearing skin and the conjunctiva. The membranous bone from the skull has been shown to undergo less resorption and greater graft volume survival as compared to endochondral bone of the iliac crest or rib. Skull bone is an ideal source of bone graft in orbital reconstruction. PMID- 11767710 TI - [Total auricle reconstruction with postauricular flap and a Medpor framework]. AB - OBJECTIVE: To introduce a new method and technique of auricle reconstruction. METHOD: The postauricular flap was designed to cover a Medpor framework for auricle reconstruction. The vascular pedicle of the flap was at the temporal part. The operation was performed on 12 patients, of whom 8 patients were with microsomia; 4 patients had total auricle defects. RESULTS: Postoperative follow up period was 8 months in average. All the 12 patients obtained satisfactory appearance of the reconstructed ears. CONCLUSION: Clinical applications showed several advantages of this method. PMID- 11767711 TI - [Modification of transnasal medial canthopexy]. AB - OBJECTIVE: To study the curative effect of transnasal medial canthopexy. METHODS: By a coronal or medial canthal incision, we applied transnasal medial canthopexy to repair medial canthal detachment. A total of 78 patients received the operation. RESULTS: Of them, 64 patients obtained satisfactory postoperative appearance with one operation; 6 patients obtained satisfactory results with two operations. The operation was unsuccessful in 8 patients. CONCLUSION: This method is one of the ideal methods of repairing medial canthal detachment, however its indications should be observed. PMID- 11767712 TI - [An experimental study of tissue engineered autologous cartilage by using an injectable polymer]. AB - OBJECTIVE: To investigate the proper cell density of tissue engineered autologous cartilage to indicate the clinical application. METHODS: The chondrocytes, isolated from mini swines' ears, were mixed with an injectable biocompatible matrix(Pluronic F127) to make the cell suspensions with the densities of 10,20, 30,40,50,60,70 x 10(6)/ml. The chondrocyte-polymer complex was injected into the subcutaneous tissue of the swines' abdomens. Each specimen was harvested and evaluated with body-mass, histological examination, and glycosaminoglycan content and type II collagen tests after 6 weeks in vivo. RESULTS: The histological examination had showed that the neo-cartilage was solid, homogenous cartilage when using 50 million chondrocytess/cc for 6 weeks. The samples with the 10 and 30 million chondrocytes/cc showed that the area of the cartilage was incomplete and separated by the remnant polymer. The mass of the samples was ranged from 30 110 mg after 6 weeks. The glycosaminoglycan content was lower from 5.8 to 9.0 percent, compared to the 9.2 percent of the normal auricular cartilage. Western Blot had presented the type II collagen in all samples. CONCLUSION: This study has demonstrated that the qutologous cartilage could be generated by using tissue engineering technique, with the histological characteristics similar to natural cartilage. Fifty million chondrocytes per cc could yield the best quality cartilage in 6 weeks. PMID- 11767713 TI - [Immunological mechanism of human alpha-interferon gene therapy for treatment of melonoma]. AB - OBJECTIVE: To investigate the possibility of alpha-INF gene therapy for treatment of melonoma. METHODS: An experimental model of fibroblast-mediated human alpha IFN gene therapy was established for treatment of melonoma and the activity of NK and M phi was determined. RESULTS: The NK and M phi activity was increasing significantly after the implantation of alpha-IFN secreted by cloning the fibroblast in vivo. Good therapeutic results could be achived if the NIH3T3-IFN alpha+ cells were combined with the IL-2/AK. CONCLUSION: The results has indicated that the fibroblast-mediated gene therapy could be good to use it for the treatment of human melonoma. More effective results could be achieved by using it in combination with IL-2. PMID- 11767714 TI - The management of minor injuries--a personal view. PMID- 11767715 TI - Bell-bottoms, platform shoes, and the nursing shortage. PMID- 11767716 TI - Family functioning in anorexia nervosa differs by subtype. AB - OBJECTIVE: This study investigated family functioning in adolescents with the restricting and bulimic type of anorexia nervosa (AN) and in healthy controls. METHOD: Fifty-one parents and their children (17 with AN and 34 healthy adolescents) completed the Family Assessment Measure, a self-report instrument that provides information about the functional strengths and weaknesses of the family and each family member. RESULTS: AN patients with the bulimic subtype and their mothers were significantly more likely to perceive family functioning as impaired than were healthy adolescents or restricting AN patients. Restricting AN patients and their families did not differ from healthy control families. CONCLUSION: The results suggest that the problems faced by bulimic patients color their and their parents' view of each other and the family. Symptomatic and personality differences between the subtypes of AN with better control, fewer symptoms, and denial of conflict characterizing restricting AN families may be reflected in family interaction styles. PMID- 11767717 TI - The interrater reliability of physical signs in patients with eating disorders. AB - OBJECTIVE: To evaluate the interrater reliability of five common signs of eating disorders. METHODS: Eating disorder patients with anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified (ED-NOS), at various stages of recovery, were evaluated for the presence or absence of lanugo hair, acrocyanosis, parotid hypertrophy, hypercarotinemia, and Russell's sign. Patients were examined by two physicians with similar experience and training. Results are analyzed for reliability using the kappa statistic. RESULTS: Kappa scores were as follows, indicating marginal reproducibility of results: lanugo hair (kappa = 0.606), acrocyanosis (kappa = 0.014), parotid hypertrophy (kappa = 0.266), hypercarotinemia (kappa = 0.101) , and Russell's sign (kappa = 0.140). CONCLUSION: The interrater reliability for individual items ranged from poor to moderate. Overall, there is marginal interrater reliability for the five common signs of eating disorders assessed. PMID- 11767719 TI - Bibliography. Current world literature. Hypertension. PMID- 11767718 TI - Gender and racial/ethnic differences in tobacco-dependence treatment: a commentary and research recommendations. AB - The preparation of the Public Health Service Report, Treating Tobacco Use and Dependence, brought to light a substantial gap in the smoking cessation literature; there is little or no research evidence regarding the success of formal tobacco-dependence treatment specific to gender or racial/ethnic status. Of the 192 articles included in the meta-analyses of the evidence-based PHS Report, none included results based on racial/ethnic group and only four reported results by gender. This commentary identifies tobacco use as a problem that crosses gender and racial/ethnic boundaries, reviews reasons that the different genders or racial/ethnic groups might require different tobacco-dependence treatments, provides suggestive evidence that both gender and racial/ethnic status influence tobacco-dependence treatment efficacy, and recommends changes and directions for future clinical research that will address gender and racial/ethnicity effects. PMID- 11767721 TI - Proceedings of the International Symposium on Combination Vaccines. 2-4 February 2000. PMID- 11767720 TI - Bibliography. Current world literature. Clinical trials. PMID- 11767722 TI - An interview with Professor David Yates. PMID- 11767723 TI - Cervical spondylotic myelopathy: diagnosis and treatment. AB - The delineation of cervical spondylotic myelopathy as a clinical entity has improved with the development of high-quality cross-sectional neuroradiologic imaging. The natural history of this disorder is usually slow deterioration in a stepwise fashion, with worsening symptoms of gait abnormalities, weakness, sensory changes, and often pain. The diagnosis can usually be made on the basis of findings from the history, physical examination, and plain radiographs, but confirmation by magnetic resonance imaging or computed tomography and myelography is necessary. Minimal symptoms without hard evidence of gait disturbance or pathologic reflexes warrant nonoperative treatment, but patients with demonstrable myelopathy and spinal cord compression are candidates for operative intervention. Both anterior and posterior approaches have been utilized for surgical treatment of cervical myelopathy. Anterior decompression frequently requires corpectomy at one or more levels and strut grafting with bone from the ilium or fibula. Multilevel laminectomies were initially used for posterior decompression but now are either combined with fusion or replaced by laminoplasty. Any operative technique requires proper patient selection and demands adequate decompression of the canal to effect neurologic improvement. Perioperative complications can be devastating in this group of high-risk patients with cervical spondylotic myelopathy, but careful attention to detail, meticulous technique, and experience can result in excellent outcomes. PMID- 11767724 TI - Effects of prework screening and early return to work programs. PMID- 11767725 TI - Abstracts from meetings of the Italian Biochemical Society. 1999. PMID- 11767727 TI - XVII Congress of the Spanish Society of Clinical Pharmacology. Seville, Spain, November 22-24, 2001. Abstracts. PMID- 11767726 TI - [Performance and simulation of intermittent decanted extended aeration treatment plants in a tropical climate]. AB - The paper discusses the design and performance of package sewage treatment plants using the Intermittently Decanted Extended Aeration Process (IDEA-Process) in a tropical climate. This hybrid SBR process has been developed overcome traditional drawbacks associated with the SBR process, such as high Sludge Volume Index, high weir loading rate for decanting, and the need to achieve a better effluent quality, especially in terms of nutrient removal. Three domestic sewage plants in Thailand has been selected for field-testing and results of analyses are presented. The average measured biological removal efficiencies in terms of BOD removal and COD removal are about 95.5% and 90% respectively, and the average total nitrogen removal efficiency is about 90%. A computer model is used to study the performance of IDEA-processes compared to results from laboratory tests. The model experience gained through this research are discussed regarding the limitations of computer models such as ASM 1 (Activated Sludge Model n degrees 1) applied to the IDEA-Process in order to develop a new computer model suitable for design and operation of package treatment plant using IDEA-Process Technology in the future. PMID- 11767728 TI - Haptic perception of parallelity in the midsagittal plane. AB - Previous studies [Perception 28 (1999) 1001; Perception 28 (1999) 781] on the haptic perception of parallelity on a horizontal plane showed that what subjects haptically perceive as being parallel deviates considerably from what is physically parallel. The deviations could be described with a subject-dependent orientation gradient in the left-right direction. The gradients found in the bimanual conditions were significantly larger (about 70%) than those in the unimanual conditions. The questions to be answered in the present study are the following: (1) Does the haptic perception of parallelity in the midsagittal plane also show systematic deviations from veridicality? (2) Are the unimanual and bimanual performances again quantitatively but not qualitatively different? The set-up consisted of a plate positioned in the midsagittal plane of the subject. The subject touched the right side of the plate with his/her right hand and the left side with the left hand. The results show again large systematic deviations. The major part of the deviations can be described by means of a subject-dependent orientation gradient in the vertical direction. The quantitative (but not qualitative) difference between the unimanual and the bimanual conditions is much larger in the midsagittal plane than in the horizontal plane. PMID- 11767729 TI - Anticipatory responses to perturbation of co-ordination in one-handed catching. AB - Anticipatory responses to perturbation have rarely been studied in the co ordination of dynamic interceptive actions. In this study, the kinematics of ball catching were examined in skilled catchers when mechanical perturbation of the catching arm was expected and unexpected. During trials where the perturbation was anticipated, participants initiated movements earlier (207 +/- 32 ms) than in randomly perturbed trials (223 +/- 34 ms). Furthermore, several individuals also tended to move their hand faster when perturbations were expected compared to baseline trials. Individual analyses revealed that three out of eight participants exhibited changes in the relative timing of the grasp phase to adapt to the specific manipulation of task constraints. Anticipatory responses were revealed in changes not only at movement initiation but also in the resulting adaptations to the co-ordination of reach and grasp phases of ball catching. When the catchers could not anticipate perturbations, movement strategies suggested the use of a continuous tracking-based mode of control rather than a prediction based mode of control. PMID- 11767730 TI - From the Centers for Disease Control and Prevention. Update: Outbreak of poliomyelitis--Dominican Republic and Haiti, 2000-2001. PMID- 11767731 TI - From the Centers for Disease Control and Prevention. Cigarette smoking among adults--United States, 1999. PMID- 11767732 TI - From the Centers for Disease Control and Prevention. Pesticide-related illnesses associated with the use of a plant growth regulator--Italy, 2001. PMID- 11767733 TI - From the Centers for Disease Control and Prevention. Influence of homicide on racial disparity in life expectancy--United States, 1998. PMID- 11767734 TI - Genomics and the transformation of neurology. PMID- 11767735 TI - JAMA patient page. Kidney failure. PMID- 11767736 TI - Author and subject indexes, volumes 236-247 (2000). PMID- 11767737 TI - Partitioning of selected antifouling biocides in the aquatic environment. AB - Following a ban on the use of tributyltin in antifouling products on small boats, a number of organic booster biocides have been utilised in conjunction with copper in antifouling paints as alternative treatments. The fate of organic compounds in the aquatic environment is closely linked to their partitioning between aqueous media and sediment. In this study, experiments were designed to investigate the partitioning and sorptive behaviour of Irgarol 1051, chlorothalonil, dichlofluanid and diuron in the aquatic environment. Factorial experiments were undertaken to determine the importance of pH, particulate matter concentration and salinity to their sorption. A Mackay fugacity model was also applied. Results demonstrated that dichlofluanid had the stronger adsorption characteristics and was predicted to bind more strongly to sediments than Irgarol or chlorothalonil. Diuron exhibited the least preference for sorptive behaviour. Sorption appeared to be enhanced by increased suspended matter, whilst salinity does not seem to play a significant role in the partitioning behaviour of these biocides. PMID- 11767738 TI - Influence of temperature on the physiological responses of the bivalve Brachidontes striatulus and its significance in fouling control. AB - Heat treatment offers an alternative method of fouling control to chlorination in power plants. In order to optimise such a procedure it is important to understand the responses of fouling organisms to elevated water temperatures. In this paper we report results of experiments on the lethal and sub-lethal effects of temperature on the bivalve Brachidontes striatulus which is one of the major foulants in the process seawater heat exchangers of Madras Atomic Power Station located at Kalpakkam, on the east coast of India. The important physiological activities, such as, oxygen consumption, filtration rate, byssus thread production and faecal matter production were studied at temperatures varying from 20 to 38 degrees C. Three different size groups [3-5 mm shell length (group 1), 6 10 mm (group 2), 11-15 mm (group 3)] of B. striatulus were used for the experiments. The results showed physiological activities were maximum at 35 degrees C, minimum at 20 and 38 degrees C. Physiological activities increased with size except for byssus thread production, which did not show any trend. Survival times showed a reduction from 30 h at 39 degrees C to < 1 h at 45 degrees C and were independent of body size. PMID- 11767739 TI - Lethal and sub-lethal effects of chlorination on green mussel Perna viridis in the context of biofouling control in a power plant cooling water system. AB - Continuous chlorination is a widely followed cooling water treatment practice used in the power industry to combat biofouling. The green mussel Perna viridis is one of the dominant fouling organisms ( > 70%) in the Madras Atomic Power Station. Mortality pattern as well as physiological responses such as oxygen consumption, filtration rate, byssus thread production and faecal matter production of three different size groups of this mussel were studied at different chlorination concentrations. At 0.7 mg l(-1) residual chlorine, 3-4 cm size mussels showed 100% mortality in 553.3 h while 8-9 cm size group mussels died within 588 h. At a relatively high level of residual chlorine (9.1 mg l( 1)), 100% mortality in 3-4 cm and 8-9 cm size groups took 94 and 114 h, respectively. All physiological activities studied showed a progressive reduction as chlorine residuals were increased from 0 to 0.55 mg l(-1). The data indicated that the green mussel can sense a residual chlorine level as low as < 0.15 mg l( 1) and complete valve closure occurs only at 0.55 mg l(-1). The paper also shows that the sub-lethal physiological responses are better indices than lethal responses in planning chlorination strategies. PMID- 11767740 TI - Degradation of microcystin toxins in a falling film photocatalytic reactor with immobilized titanium dioxide catalyst. AB - The increasing incidence of algal blooms in fresh water supplies and the consequent possibility of cyanobacterial microcystin contamination of potable water is a cause of recent concern. Heterogeneous photocatalytic oxidation forms part of a family of advanced water treatment technologies comprising the generation of reactive oxidizing species in water media and results in the complete oxidative degradation (mineralization) of organic pollutants to yield carbon dioxide, water and inorganic ions. A new experimental laboratory-scale 'falling film' reactor has been developed to study the photocatalytic degradation of microcystins in aqueous solution. The reactor consisted of a fiberglass sheet impregnated with immobilized titanium dioxide (TiO2) catalyst over which the microcystin solution was pumped (as a falling film) while being irradiated from UV-C germicidal lamps. The design of the system obviated the necessity to separate suspended catalyst from treated water as required in slurry reactors. The photocatalytic degradation was characterized by pseudo-first order reaction kinetics. Rapid degradation of microcystins LR, YR and RR was observed in natural lake water with half lives less than 10 min, while even faster rates were achieved in laboratory distilled water. Although low pH (pH 3) marginally improved reaction rates. the presence of radical scavengers such as sulfate ions was detrimental to the photocatalytic oxidation process. PMID- 11767741 TI - Desorption kinetics of PCP-contaminated soil: effect of temperature. AB - A thermally enhanced pump-and-treatment method for pentachlorophenol (PCP) contaminated soil and groundwater has shown potential advantages over the traditional pump-and-treatment method. Studies on the desorption kinetics of PCP from aquifer soil are the first step toward quantitative assessment of the newly proposed method. Five series of desorption batch tests were conducted at different temperatures, and the test results were analyzed by linear regression to determine the best-fit kinetic model for PCP desorbed from the contaminated field soil under all temperature conditions. The first-order kinetic model, parabolic diffusion model, and modified Freundlich model were discussed in linear regression work. A modified Freundlich model was found to describe the PCP desorption kinetics from soil in consideration of a temperature effect. PMID- 11767742 TI - The validity of the Gammarus:Asellus ratio as an index of organic pollution: abiotic and biotic influences. AB - In freshwaters. Gammarus spp. are more sensitive to organic pollution than Asellus spp. and the relative abundance of the two taxa has been proposed as a pollution index. We tested the validity of this by examining the relationship between the Gammarus: Asellus (G : A) ratio and (1) a suite of physico-chemical variables. (2) established biotic (average score per taxon, ASPT) and richness (species richness (S) and Ephemeroptera, Plecoptera and Trichoptera families richness (EPT family richness)) indices generated from the macroinvertebrate community. In addition, we investigated a suspected biotic interaction, predation, between Gammarus and Asellus. Both univariate and multivariate analyses showed that the G: A ratio was sometimes responsive to changes in parameters linked to organic pollution, such as BOD5 and nitrate levels. However, the G : A ratio also appeared responsive to variables not directly linked to organic pollution, such as conductivity and distance from source. There were significant positive correlations among the G : A ratio and the ASPT, S and EPT, indicating that changes in the relative abundances of Gammarus and Asellus were reflected in changes in the pollution sensitivity and richness of the wider macroinvertebrate community. A laboratory experiment revealed significant predation of Asellus aquaticus juveniles by Gammarus duebeni celticus adults, but no reciprocal predation. We propose that the G: A ratio may be useful as a crude measure of organic pollution that could supplement more complex indices in a multimetric approach to pollution monitoring or be used for monitoring individual sites, where a simple technique is required for monitoring purposes over a period of time. Also, we urge recognition of the possible role of biotic interactions among taxa used in the generation of pollution indices. PMID- 11767743 TI - Oilfield wastewater treatment by combined microfiltration and biological processes. AB - This work deals with the treatment of offshore oilfield wastewater from the Campos Basin (Rio de Janeiro State, Brazil). After coarse filtration, this high saline wastewater was microfiltrated through mixed cellulose ester (MCE) membranes, resulting in average removals of COD, TOC, O&G and phenols of 35%, 25%, 92% and 35%, respectively. The permeate effluent was fed into a 1-L air-lift reactor containing polystyrene particles of 2mm diameter, used as support material. This reactor was operated for 210 days, at three hydraulic retention times (HRT): 48, 24 and 12h. Even when operated at the lowest HRT (12 h), removal efficiencies of 65% COD, 80% TOC, 65% phenols and 40% ammonium were attained. The final effluent presented COD and TOC values of 230 and 55 mg/L, respectively. Results obtained by gas chromatography analyses and toxicity tests with Artemia salina showed that a significant improvement in the effluent's quality was achieved after treatment by the combined (microfiltration/biological) process. PMID- 11767744 TI - Abstracts of the 5th International Symposium on Hodgkin's Lymphoma. 22-25 September 2001. Cologne, Germany. PMID- 11767745 TI - Nuclear envelope and nuclear matrix: interactions and dynamics. AB - The peripheral nuclear lamina is located near the nuclear inner membrane and consists of lamin filaments and integral membrane proteins, including the lamin B receptor and various isoforms of lamina-associated polypeptides (LAP) 1 and 2. Several nuclear membrane proteins also interact with chromatin proteins BAF and Hp1. Lamins in the nuclear interior associate with at least one soluble (non membrane-bound) LAP2 isoform named LAP2alpha. The internal lamins, together with Tpr-based filaments that connect to nuclear pore complexes, are proposed to be major structural elements of the internal nuclear matrix. We describe the structural links between the peripheral lamina and the internal nuclear matrix that are thought to be mediated by LAP2 family members, filament protein Tpr and nucleoporin Nup153. These findings are discussed in relation to human diseases that arise from mutations in nuclear lamina proteins. PMID- 11767746 TI - [2001 Scientific Pathology Conference. 12-16 November 2001, Paris, France. Abstracts]. PMID- 11767747 TI - [The struggle against venereal disease in Lodz at the turn of the 19th century]. AB - At the turn of the 19th century in Lodz - with its poor sanitary conditions - venereal diseases (including the most dangerous, syphilis) were amongst the infectious and social diseases which were a great danger to the health and life of its inhabitants. Prostitution, which was a source of income for low-paid or unemployed women, contributed in great measure to the spread of infection. Bad housing conditions, abuse of alcohol, unawareness of danger and carelessness of treatment were also conducive to venereal diseases. The State authorities, who were obliged to struggle against venereal diseases, did so by repressive and humiliating police methods and by the introduction of controls in 1894 involving the registration and compulsory medical examination of prostitutes. Considering the lack of compulsion (except for prostitutes), venereal patients were hospitalized on a limited scale in only the general, specialist and constantly overcrowded Szpital Sw. Aleksandra (St. Alexander Hospital) - the prostitutes at their own expense and the poor at the expense of the municipality. The rich underwent treatment discreetly, in the surgeries and infirmaries of privately practising doctors. The lasting danger of venereal diseases prompted initiatives by doctors- philanthropists, members of Lodzkie Towarzystwo Lekarskie (the Medical Society of Lodz) and the local branch of Warszawskie Towarzystwo Higieniczne (the Hygienic Society of Warsaw). By their lectures, brochures and articles in medical periodicals they popularized their views on the causes; prevention and the struggle against venereal diseases. They were critical of the police and medical surveillance and the struggle against prostitution amongst juvenile girls and recommended the introduction of public, cost - free and obligatory treatment of the sick. PMID- 11767748 TI - [Physicians, who studied in Poznan University, as organizers of medical care in Gdynia in the interwar period]. AB - This paper describes some physicians who graduated from Poznan University and who were connected with medical care in Gdynia. PMID- 11767749 TI - [The medical staff in the Polish Legions]. PMID- 11767750 TI - [Polish pharmaceutical organisations in Great Britain in the years 1943-1949]. AB - In August 1943 a group of Polish pharmacists fighting in the armed forces in Great Britain established The Scientific Society of Polish Pharmacists of the Armed Forces. It was a military organisation. In September 1945 a professional organisation, named the Polish Pharmaceutical Association Abroad was formed in Scotland. The first chairman was Master of Pharmacy, Mateusz Bronislaw Grabowski. This is the first study devoted to this subject, and the lecture will be prepared on the basis of material brought from London. PMID- 11767751 TI - [The history of tranquilizing and sleeping drugs]. PMID- 11767752 TI - [The medical staff in Koscian in the period "PRL", 1945-1989]. PMID- 11767753 TI - [Letters from professor Benedykt Dybowski to Professor Jan Grochmalicki, his former student and my father]. AB - A valuable contribution to familiarization with the character of professor Benedykt Dybowski (1833-1930), a physician and zoologist, sentenced to exile in Traugutt's trial, explorer of Siberia and professor of Jan Kazimierz University in Lwow, can be made by a two preserved letters from professor Dybowski to Jan Grochmalicki (1883-1936), who was his former student and the closest co-worker enjoying his special confidence. The exchange of letters began in April 1919 at the moment of professor Grochmalicki's moving to Poznan where he became head of the Department of Zoology at the University of Poznan, which was just established, and professor Dybowski remained in besieged Lwow. In the last letter written in June 1929, ailing 97-years old professor Dybowski says his farewells in the words "I am going at a quick pace to Nirvana". The letters throw light both on the difficult time of the birth of the Second Republic of Poland and rich personality of Benedykt Dybowski. PMID- 11767754 TI - [The Marian Kawski's monumental pharmacy in Sanok]. PMID- 11767755 TI - [Disease occurrence in the Polish Army during the Polish-Bolshevik War, 1919 1921]. AB - The publication is a presentation of the group of diseases concomitant with the military operations of the years 1919-1921 - the most important war for the Polish Republic in the XX century. The range of diseases was specific because of the area and the kind of operations. This paper describes the methods of disease prevention and treatment employed by the Polish Army at that time. PMID- 11767756 TI - [Problems of Doctor Judym's peers]. AB - This paper is a work on the health conditions of the inhabitants of Rzeszow and the surrounding area in the second half of the 19th century as based on the mortality analysis. A comparison and contrast has been made between the daily work of a doctor nowadays and a hundred years ago. The issues have been presented at various levels, with reference to the political, socio-economic and cultural relations existing at that time. The work is enhanced with additional comments on the doctor's profession and the problem of diagnostic difficulties as well as the possibility of making a mistaken judgement. Additionally, the definition of death at that time and at present has been formulated. The issues of colleague solidarity, ethical and moral issues and the activities of the Doctors' Association over the above mentioned period are also discussed. I noted the "plague" of the time which was the provision of medical treatment by the unqualified. The above considerations may be a starting point for the present, popular discussion on the principles of a doctor's ethics and duty. PMID- 11767757 TI - [Assistant Professor Jozef Szymanowicz Md. PhD.: his life and activities]. AB - The paper presented the life and activities of Jozef Szymanowicz MD. PHD (1886 1946). He was one of the closest collaborators of Professor Aleksander Rosner, Head of the Clinic of Obstetrics and Gynaecology and a pioneer of Polish endocrinological gynaecology. Jozef Szymanowicz, one of the most promising young researchers headed the Clinic after the death of Professor Rosner (1930-1931). Until the outbreak of the Second World War he was Head of the Gynaecology Ward of the Saint Lazarus Hospital in Cracow. He left several very interesting scientific papers for the next generation. PMID- 11767758 TI - [The ethical message of the history of medicine as a guideline for modern medicine]. AB - To fulfill its role in the humanization of today's medicine is the correct subjective relationship between doctor and patient, the doctor and society, the teaching of the history of medicine should pay more attention to medicine as an art. This conception carries the ethical message of humanism and humanitarianism towards the patient. The history of medicine as an academic subject focuses mainly on the history of approaches, conceptions, outstanding discoveries in the domain of physiology and anatomy etc. However, I believe that to achieve the aim of humanizing medicine, we should adopt an interdisciplinary approach. Therefore teaching the history of medicine and pharmacy, I try to consider its particular aspects from the philosophical-ethical perspective. In this way the focus of attention shifts to the patient his experience of suffering, his illness and death. What made me choose this perspective was the study of the Polish 19th Century approach to the history and philosophy of medicine, in which the patient and his health was an end in itself. PMID- 11767759 TI - Controversy over accuracy of compatibility chart. PMID- 11767760 TI - Using jugular venous catheters in patients with traumatic brain injury. AB - Sjo2 monitoring has several important limitations, such as catheter reliability, sampling error, and lack of regional specificity. However, combining Sjo2 monitoring with other available technologies can facilitate optimization of treatment and improve outcomes in patients with severe brain injuries. PMID- 11767762 TI - Fostering use of the Internet for research of clinical issues. PMID- 11767761 TI - Charcoal hemoperfusion via a continuous venovenous hemofiltration circuit to treat carbamazepine overdose. PMID- 11767763 TI - Understanding the neonatal immune system: high risk for infection. AB - Neonates are vulnerable to infection from prenatal and postnatal exposure to microorganisms. The immaturity of the immune system in neonates and illness and/or prematurity place these infants at significant risk for bacterial invasion and systemic infection. Long-term sequelae include, but are not limited to, prolonged hospital stays and increased risk of neurodevelopmental problems. Nurses must understand the function of the immune system and the disadvantages unique to newborn infants to be able to provide education to others and appreciate the need for vigilant monitoring and protection of these infants. PMID- 11767765 TI - Findings from reader survey on RN shortage: "I still love nursing, but ...". PMID- 11767764 TI - Guidelines for the management of severe head injury: clinical application and changes in practice. PMID- 11767766 TI - Turning patients on mechanical ventilation. PMID- 11767767 TI - Case scenario complications reinforce confidence at the bedside. PMID- 11767768 TI - Ophthalmic blocks at the medial canthus. PMID- 11767769 TI - Does early preload adaptation exist in patients with septic shock? PMID- 11767770 TI - Seeking an integrated model of anesthetic action. PMID- 11767771 TI - What are "relevant" concentrations? PMID- 11767772 TI - Should imaging studies be routinely performed prior to epidural steroid injections? PMID- 11767773 TI - Difficult laryngoscopy due to the abnormal palatoglossal arch. PMID- 11767774 TI - A new technique of fiberoptic intubation through a standard LMA. PMID- 11767775 TI - Claude Bernard, the spinal cord, and anesthesia. PMID- 11767776 TI - Coordinated care reduces functional declines in hospitalized elderly patients. PMID- 11767777 TI - Improved stroke care could cut costs and save lives, study indicates. PMID- 11767778 TI - Shorter hospital stays may harm elderly pneumonia patients. PMID- 11767779 TI - Consensus statement outlines adjuvant treatment options for women with breast cancer. PMID- 11767780 TI - [Counteracting effects of intermittent head-up tilt on simulated-weightlessness induced atrophy of anti-gravity muscles]. AB - Objective. To study the efficacy of intermittent + Gz (45 degrees head-up tilt, HUT) exposures in preventing or alleviating atrophic changes in hind limb muscles induced by simulated weightlessness. Method. Male Sprague-Dawley (SD) rats were assigned randomly to one of three groups: simultaneous control (CON), simulated weightlessness (SUS), and SUS plus 6 h/d HUT (SUS + HUT). Muscles examined included soleus (SOL), medial gastrocnemius (correction from grastrocnemius) (MG), lateral gastrocnemius (LG) and extensor digitorum longus (EDL). Sections were treated with an adenosinetriphosphatase (ATPase) stain or alkaline phosphatase stain. The cross-sectional areas (CSA) of fibers, the relative proportion of type I fiber and the ratio of capillaries/fibers (C/F) were measured using Leica image analysis system. Result. Compared with CON, the wet weight of hind limb muscles in SUS were significantly reduced. The changes of wet weight in different groups were various. The C/F ratios of all muscles were significantly reduced. SUS + HUT rats showed significant increases in SOL and MG wet weight, and the relative counter-effects of intermittent HUT were 93.4% and 34.8%, respectively. In SUS + HUT group, the CSA of both type I and II fibers and relative proportion of type I fibers were completely recovered in SOL, and partially recovered in MG, while the counter-effects were much less obvious in the fibers of LG and EDL. However, HUT resulted in a significant recovery of the C/F ratios in all muscles. Conclusion. The present study demonstrated that intermittent HUT is effective in counteracting the atrophy induced by simulated weightlessness. The result that reactivity to HUT varied among different muscles suggests that the intermittent artificial gravity should be complemented with other countermeasures. PMID- 11767781 TI - [Effects of noise and music on EEG power spectrum]. AB - Objective. To observe the effect of noise and music on EEG power spectrum. Method. 12 healthy male pilots aged 30 +/- 0.58 years served as the subjects. Dynamic EEG from 16 regions was recorded during quiet, under noise or when listening to music using Oxford MR95 Holter recorder. Changes of EEG power spectrum of delta, theta, alpha1, alpha2, beta1 and beta2, frequency components in 16 regions were analyzed. Result. The total alpha1 power was significantly decreased, while the total theta power was significantly increased when listening to music; It implies that the interhemispheric transmission of information in the frontotemporal areas might be involved. Conclusion. The changes of the EEG power spectrum were closely related to man's emotions; relaxation was associated with music; Individual difference exists in the influence of sound on EEG. PMID- 11767782 TI - [Effects of some physical training on vestibular function]. AB - Objective. To study the effects of active vestibular conditioning by some physical training on the vestibular function. Method. 10 subjects were given five kinds training gyro wheel, hanging ladder, ripple wood, four column swing and rotating swing for two weeks. Vestibular experimental tests were given before and after training. Result. After physical training, subjects' linear acceleration tolerance time increased significantly, the result of computer dynamic equilibrium posturegraphy demonstrated that the sway of body center of gravity decreased significantly when subjects maintained their equilibrium by both vestibular and visual information. Conclusion. The linear acceleration physical training methods used in this experiment have positive effects, while the methods of angular acceleration training need further investigation. PMID- 11767783 TI - [Molecular analysis of space mutant line of kidney bean]. AB - Objective. To identify the occurrence of gene mutant in mutant lines in the offspring of Kidney bean seeds under space flight condition. Method. Kidney bean seeds were carried onboard a recoverable satellite for 15 days in space and were planted on the ground after recovery. Five mutant lines showing variation in the form of leaf blade and their parents were analyzed with RAPD technique. Result. 50 random 10-mer primers were used in this study, among which 20 primers generated 180 polymorphic DNA bands, their size ranged from 200 bp to 2000 bp. 3 primers amplified obviously different bands in the DNA of mutant lines in comparison with that of the control. Conclusion. This is the first molecular analysis of the mutant lines of Kidney bean generated by space mutagenesis at DNA level. The result of RAPD analysis indicated that distinct variations were demonstrated in the DNA of mutant lines as compared with that of the original control. PMID- 11767784 TI - [Effects of acute hypoxia on plasma lactic acid and lactic dehydrogenase content in pilots]. AB - Objective. To study the effect of acute moderate hypoxia on plasma lactic acid (LA) and lactic dehydrogenase (LDH) content in pilots. Method. Concentrations of plasma LA and LDH were measured by colorimetry in 16 healthy male pilots in the early morning (6:00 a.m.), following acute moderate hypoxic exposure (10:00 a.m.) and 6 hours after returned to the ground (4:00 p.m.). 16 healthy male ground people served as control group, and their plasma LA and LDH contents were assayed at corresponding time. Result. Plasma LA after moderate hypoxic exposure in the pilot group was significantly higher than that at 6:00 a.m., 4:00 p.m., and control group (P < 0.01). While the content at 6:00 a.m., 4:00 p.m. in pilot group was not significantly different from the control group (P > 0.05). The content of plasma LDH after moderate hypoxic exposure in the pilot group was not significantly higher than that at 6:00 a.m., 4:00 p.m., and control group (P > 0.05). Conclusion. Acute moderate hypoxia can make the plasma LA content increase in pilots, and reach to the normal level within 6 h. While the LDH content has no significantly change. PMID- 11767785 TI - [Approximate entropy and its application in heart rate variability analysis]. AB - Objective. To introduce approximate entropy in the analysis of heart rate variability, and to discuss the changes of the complexity of cardiovascular system during orthostatic standing posture. Method. ECG of 8 subjects were recorded during supine and orthostatic standing postures. Approximate entropy was used to analyze HRV. Result. Compared to supine before orthostatic standing posture, R-R intervals at 0-5 min, 5-10 min, 10-15 min and 15-20 min during orthostatic standing posture were decreased significantly, while approximate entropy at 0-5 min and 15-20 min decreased significantly. It showed that the complexity of cardiovascular system was decreased and the modulation of cardiovascular system changed. Conclusion. It is feasible that approximate entropy be used for heart rate variability analysis. PMID- 11767786 TI - [Heart morphologic state in retired fighter pilots]. AB - Objective. To study the heart morphology in the retired fighter pilots, and to provide clinical evidence for protection combined G-loads (+ Gz), heat, noise, hypoxic and vibration stress induced cardiac structural damage. Method. Parameters of heart morphology were studied using Doppler echocardiography in 40 retired fighter pilots with 40 veteran cadres as control. Result. LVDd, LVDs, LADs, LVEDV, LVPWs and LVM in pilot group were somewhat higher than those in control group (NS); while IVSs and LVMI in pilot group were slightly lower than those in control group (NS); LVESV, aortic valve area, internal diameter of the ring and sinus in pilot group were significantly higher than those in control group (P < 0.05). Conclusion. Analysis of the results revealed no pathomorphologic damage of the heart. It suggest that all the variations can be regarded as adaptive changes due to the effects of the combined environmental factors experienced in long time flying. PMID- 11767787 TI - [Data analysis of 492 times centrifuge examination]. AB - Objective. To sum up the experiences and to find the regularity of centrifuge examinations. Method. The data of nine years of centrifuge examination (from 1988 to 1996) of pilots who suffered from black out or LOC frequently were analyzed. Result. There were totally 492 times centrifuge examinations. First centrifuge examination included 229 pilots, 49 qualified, 180 unqualified. Second centrifuge examination included 263 pilots, 50 qualified, 213 unqualified. The pilots were all male. The average age of first centrifuge examination was 29.27 +/- 4.87 years. Average flying time was 1015.24 +/- 131.89 h. 68.7% of their plane was JJ 6 or above. Conclusion. Most pilots undergoing centrifuge examination these nine years were 26-35 year old, and had flown for 601-1200 h. The planes they flew are mostly high-performance fighter aircraft. Close attention must be paid to pilots under similar condition by the flight surgeon. It is recommended that the special equipment of G-tolerance training should be added to the fighter aircraft units. PMID- 11767788 TI - [Changes of learning and memory function under weightlessness or simulated weightlessness]. AB - The work efficiency of astronauts has an intimate connection with the brain function state during space flight. The research results of the learning and memory mechanism of the brain in recent years were introduced. The effects of weightlessness or simulated weightlessness on brain's learning, memory, focused attention and many other higher neural activities and on the relative neural transmitters were summarized. Several research aspects were put forward in the future. PMID- 11767789 TI - [Changes in electrocardiogram and cardiac phase during various stages in foreign manned spaceflight activities and the analysis of their possible mechanisms]. AB - Electrocardiography (ECG) is still the only method for continuous medical observation during various stages of foreign manned spaceflight activities, and it also serves as an important item for medical monitoring in the project for manned spaceflight activities in our country. With electrocardiography, pulse or heart rate (one of the four life signs) and cardiac function can continuously be observed. Cardiac phase relative to ECG is a main index reflecting cardiac function. Understanding of the results of ECG and cardiac phase and their mechanisms during various stages of foreign manned spaceflight activities will be helpful in establishing emergency measures in the course of manned spaceflight activities in our country. PMID- 11767790 TI - Amid controversy, panel recommends postmastectomy radiation therapy for breast cancer patients with limited lymph node involvement. PMID- 11767791 TI - Program measures mental health outcomes. PMID- 11767792 TI - New patient safety standards require up-front identification of likely medical errors. PMID- 11767793 TI - Statement outlines prevention measures for ischemic stroke. PMID- 11767794 TI - Study finds significant differences in breast cancer treatment. PMID- 11767795 TI - Low daily aspirin doses reduce risk of blood clots as effectively as higher doses. PMID- 11767797 TI - Internet and telephone-based congestive heart failure program as effective as and cheaper than traditional one, study says. PMID- 11767798 TI - The perceptions of Lutheran pastors toward prenatal genetic counseling and pastoral care. AB - The purpose of this study is to explore a theological perspective toward genetic counseling. A survey was sent to 207 ministers within the Evangelical Lutheran Church of America (ELCA), to determine their perspectives toward four different scenarios in a prenatal genetic counseling setting. The four different scenarios included situations involving Huntington disease, Down syndrome, trisomy 18, and anencephaly. Nearly all ELCA Lutheran pastors perceived genetic counseling as beneficial and useful and wanted to be involved in the decision-making process for whether or not to terminate pregnancy. Their views toward termination of pregnancy varied depending on the severity of the genetic abnormality. Severity in this study was based upon life compatibility. As the severity of the genetic abnormality increased, the percentage of Lutheran pastors who viewed termination as an option increased from 23% (Down syndrome) to 62% (anencephaly). A better understanding of how spiritual leaders view genetic counseling would provide an insight into how genetics and religious beliefs together play a significant role in shaping the decisions of those faced with abnormal pregnancies. PMID- 11767799 TI - Factors influencing patients' decisions to decline cancer genetic counseling services. AB - Little is known about the factors influencing patients' decisions about whether to utilize cancer genetic counseling services. The purpose of this study is to identify potential barriers to broad utilization of such services. Of a total of 136 decliners of cancer genetic counseling services at our institution, 117 were deemed eligible to participate. Of these, 73 were randomly selected for study. A total of 37/73 (51%) agreed to participate in a semistructured telephone survey designed to assess the factors that impacted their decisions to decline cancer genetic counseling. An interview script, composed of both closed- and open-ended questions was used to direct the survey. Interviews were audiotaped. Responses to open-ended questions were content analyzed. Of the participants, 34 were female and 36 were Caucasian. Seventy-two percent of the participants were between ages 36 and 55 years. Participants cited the following reasons for choosing not to proceed with cancer genetic counseling: concern over health insurability for self or family (n=15); cost (n=12); emotional impact on self or family (n=11); no perceived benefit (n=11); and time commitment (n=9). These data provide an understanding of patient's attitudes and concern impacting their decisions to decline cancer genetic counseling. This information provides guidance for the development of interventions designed to limit barriers among patients referred for such services. PMID- 11767800 TI - A survey of genetic counselors' use of informed consent documents for prenatal genetic counseling sessions. AB - Thirty six members of the Prenatal Diagnosis Special Interest Group of the National Society of Genetic Counselors were interviewed about their use of informed consent documents for the genetic counseling component of their prenatal genetic counseling sessions and their perceptions of the utility and feasibility of such documents. Major findings include (1) None of the genetic counselors currently used a consent document describing the genetic counseling component of the session itself; (2) Only three participants stated that they had ever used an informed consent document for this component of the session; (3) They disagreed about the importance and usefulness of such a document; (4) There was variability in their reported likelihood of using a document if one were available; (5) There was a fair amount of agreement about the types of information to include on an informed consent document for genetic counseling; over half of the sample endorsed 8 of 10 topics; and (6) Participants identified 10 obstacles to using such a document. Recommendations for genetic counseling practice, policy, and research are given. PMID- 11767801 TI - Prenatal diagnosis for inherited deafness--what is the potential demand? AB - Genetic testing for inherited deafness is now available within some genetics centres. This study used a structured questionnaire to assess the potential uptake of prenatal diagnosis (PND) for inherited deafness, and document the opinions of deaf and hearing individuals toward PND and termination of pregnancy (TOP) for hearing status. Participants were self-selected from the whole of the UK, of whom 644 were deaf, 143 were hard of hearing or deafened, and 527 were hearing individuals who had either a deaf parent or child. The results showed that 21% of deaf, 39% of hard of hearing and deafened, and 49% of hearing participants said they would consider PND for deafness. Six percent of deaf, 11% of hard of hearing and deafened, and 16% of hearing participants said they would consider a TOP if the fetus was found to be deaf. Two percent of deaf participants said they would prefer to have deaf children and would consider a TOP if the fetus was found to be hearing. PMID- 11767802 TI - Ethical and professional challenges posed by patients with genetic concerns: a report of focus group discussions with genetic counselors, physicians, and nurses. AB - Ninety-seven physicians, nurses, and genetic counselors from four regions within the United States participated in focus groups to identify the types of ethical and professional challenges that arise when their patients have genetic concerns. Responses were taped and transcribed and then analyzed using the Hill et al. (1997, Counsel Psychol 25:517-522) Consensual Qualitative Research method of analysis. Sixteen major ethical and professional domains and 63 subcategories were identified. Major domains are informed consent; withholding information; facing uncertainty; resource allocation; value conflicts, directiveness/nondirectiveness; determining the primary patient; professional identity issues; emotional responses; diversity issues; confidentiality; attaining/maintaining proficiency; professional misconduct; discrimination; colleague error; and documentation. Implications for practitioners who deal with genetic issues and recommendations for additional research are given. PMID- 11767803 TI - New role for institutional review boards when reviewing international projects. PMID- 11767804 TI - IRBs and financial conflict of interest. PMID- 11767805 TI - Relatives of subjects claim that researcher indifference led to harm. PMID- 11767806 TI - Conserving blood in the intensive care unit. PMID- 11767807 TI - Canadian guidelines for cardiac rehabilitation and cardiovascular disease prevention are available. PMID- 11767808 TI - The risks of exercise training. PMID- 11767809 TI - Psychosocial characteristics after acute myocardial infarction: the ENRICHD pilot study. Enhancing Recovery in Coronary Heart Disease. AB - PURPOSE: Psychosocial factors, such as emotional distress and social isolation, have been increasingly recognized as important risk factors for patients' recovery from acute myocardial infarction (AMI). This study examined age, gender, and ethnic differences in depression and general distress, social support, and health-related quality of life after AMI. METHODS: Data came from a series of 88 patients aged 62.1 +/- 14.2 years (46% female) who were hospitalized for AMI at eight different US clinical centers participating in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Pilot Study. Standardized psychometric measures were administered to assess three psychosocial domains: (1) depression and general distress (mental health functioning), (2) social support, and (3) health related quality of life. Multivariate analysis of variance was used to examine the effects of age, gender, and ethnic differences in each of the three psychosocial domains. RESULTS: Female patients reported higher levels of depression and distress compared with male patients (P = .040). Gender differences in mental health functioning differed by age (P = .046), with the greatest differences observed among younger female patients. Older patients (P = .014) and female patients (P = .025) reported lower levels of social support compared with younger and male patients, respectively. Minority patients did not differ from nonminority patients in mental health functioning or social support, and there were no significant differences in post-AMI quality of life on the basis of age, gender, or ethnicity. CONCLUSIONS: The psychosocial risk profile after AMI may be different for male and female patients, and interventions may need to take account of each gender's specific needs. PMID- 11767810 TI - Self-efficacy, psychosocial factors, and exercise behavior in traditional versus modified cardiac rehabilitation. AB - BACKGROUND: Self-efficacy and social support are established determinants of exercise adherence and have potential usefulness for tailoring independent exercise regimens for cardiac patients. Highly supervised traditional cardiac rehabilitation programs may be a barrier for independent exercise self-efficacy in low - and moderate-risk patients. PURPOSE: The authors evaluated changes in psychosocial measures including self-efficacy and social support in 80 cardiac patients with low to moderate risk randomized to a traditional cardiac rehabilitation protocol (TP) or modified protocol (MP). These measures also were assessed for their potential to predict subsequent exercise behavior. METHODS: The TP (n = 38) emphasized a supervised exercise regimen and included continuous electrocardiogram (ECG) monitoring for 3 months. The lower cost MP (n = 42) emphasized independent exercise and included group education/support meetings, and gradually weaned patients from continuous ECG monitoring and direct medical supervision. RESULTS: Repeated measures analyses of variance indicated that MP patients had higher levels of self-efficacy for independent exercise without continuous ECG monitoring (P < .05). No other protocol differences were found. Multiple regression analyses using the pooled sample (excluding dropouts) indicated that self-efficacy for independent exercise was the only significant predictor of exercise over 6 months (R2=.28 [adjusted R2= .221 P < .01). In contrast to previous reports, social support for exercise was not a significant predictor of exercise behavior. CONCLUSIONS: These findings suggest cardiac rehabilitation programs for low- and moderate-risk patients should emphasize educational and patient monitoring methods that promote patient self-efficacy for independent exercise. Programs that emphasize highly supervised exercise including longer term use of continuous ECG monitoring may impair self-efficacy for independent exercise. Longer-term studies are needed to fully determine the value of using psychosocial measures for designing individualized exercise programs and predicting long-term exercise behavior in cardiac patients. PMID- 11767811 TI - Modified protocols for cardiovascular rehabilitation and program efficacy. PMID- 11767812 TI - Temporal trends and associated factors of inpatient cardiac rehabilitation in patients with acute myocardial infarction: a community-wide perspective. AB - PURPOSE: Cardiac rehabilitation (CR) has been shown to be an important therapeutic intervention after the development of acute myocardial infarction (AMI), but historically has been underused. Inpatient CR often represents cardiac patients' first exposure to risk factor modification education and acts as a gateway to outpatient programs. METHODS: The authors performed a longitudinal study of the use of inpatient CR in 5204 Worcester residents hospitalized with validated AMI in seven 1-year periods between 1986 and 1997. RESULTS: The overall rate of referral to inpatient CR was 68%, with a slight decline in use to less than 60% in the authors' most recent study year of 1997. Referred patients were significantly more likely to be younger, male, or enrolled in a health maintenance organization; they were less likely to have a history of heart failure or stroke. They were significantly more likely to receive medications shown to be of benefit in the management of AMI and to undergo cardiac interventional procedures. In 1997, patients participating in inpatient CR were more likely to have documented inpatient counseling about nutrition, exercise, smoking, and stress reduction. DISCUSSION: The results of this multihospital community-wide study suggest relatively stable, but recently decreasing, use of inpatient CR over the past decade. Women and the elderly are underrepresented in these programs. Patients not referred to inpatient rehabilitation were less likely to be prescribed effective cardiac medications and undergo risk factor modification counseling prior to discharge. Further studies are needed to better understand the reasons for patient exclusion from the benefits of inpatient CR. PMID- 11767813 TI - Underserved populations: challenge for the new millennium. PMID- 11767814 TI - Effects of advance care education in cardiovascular rehabilitation programs: a prospective randomized study. AB - PURPOSE: To determine the effect of advance care education provided to patients enrolled in cardiovascular rehabilitation (CVR) programs and assess patients' acceptance of the educational program. METHODS: In a multicenter, prospective, randomized study, the authors administered two questionnaires 6 months apart to 284 patients enrolled in 14 CVR programs in 11 states. An educational group (99 subjects) participated in educational programs related to advance care planning and received advance directive forms after completing the first questionnaires; 185 subjects served as controls. Primary outcomes were completion of patient physician discussions of end-of-life issues and patient confidence that their end of-life wishes were understood by their physicians. Secondary outcomes were completion of formal advance directives and patient acceptance of the educational program. RESULTS: Both the educational and control groups demonstrated a larger proportion of patients at the end of the study, compared with the amount at the beginning of the study, who had completed living wills, durable powers of attorney for healthcare, and discussions with their physicians about advance directives and life support care. These outcomes were not observed more commonly after the educational intervention. Neither groups gained confidence, however, that their physicians understood their end-of-life wishes. Only 8.6% of patients had a negative response to the educational program. CONCLUSIONS: Advance care education is well received by patients enrolled in CVR programs. Enrollment in CVR promotes advance care planning to a small but measurable degree CVR rehabilitation programs appear to be acceptable sites for advance care planning but further research is needed to develop effective educational interventions. PMID- 11767815 TI - The CAPRI story:two decades of innovation and service. PMID- 11767816 TI - Personality in cultural context: methodological issues. AB - Methodological issues in cultural and cross-cultural personality research are described. A taxonomy of these studies is presented, based on whether a study is exploratory or tests hypotheses, and whether or not contextual information is measured. Core methodological issues are bias and equivalence: a taxonomy and a brief overview of statistical procedures to examine equivalence are presented, with a focus on procedures for assessing structural equivalence (i.e., similarity of meaning of an instrument across cultures). Examples are given of studies in which cultural and cross-cultural approaches, often seen as antithetical, have been fruitfully integrated. Finally, multilevel models are described in which personality characteristics are examined at individual and cultural level. PMID- 11767817 TI - Personality and culture: demarcating between the common and the unique. AB - Four traditions in research on personality and culture are distinguished: (i) the culture-and-personality school and recent relativistic perspectives, (ii) the trait approach, (iii) interactionistic orientations, and (iv) situationist approaches. Next, the first two of these traditions are evaluated to ascertain how much variance is explained by culture. Thereafter, it is argued that the (questionable) focus on explanations with a high level of inclusiveness or generality is a major reason for the near absence of situationist interpretation of cross-cultural differences. Finally, three possible strategies are discussed to bridge the gap between relativism (emphasizing differences) and universalism (assuming basic similarities). A suggestion is made as to how both approaches can be valuable when unexplainable, as well as explainable variances, in cross cultural personality research are taken seriously. PMID- 11767818 TI - Introduction. Culture and Personality. PMID- 11767819 TI - Culture and personality studies, 1918-1960: myth and history. AB - The field known as "culture and personality studies" in the middle decades of the 20th century was a precursor of contemporary cross-cultural research on personality. Its rejection by anthropologists and sociologists after 1950 was accompanied by stereotypes that have hardened into myth and obscured its character and relevance for contemporary investigators. This article dispels some prevalent misconceptions (concerning its chronology, its theoretical unity, its positions on individual differences and its relationship to Freudian psychoanalysis) and proposes a tentative explanation of its decline. PMID- 11767820 TI - Trait psychology and culture: exploring intercultural comparisons. AB - Personality traits, studied for decades by Western personality psychologists, have recently been reconceptualized as endogenous basic tendencies that, within a cultural context, give rise to habits, attitudes, skills, beliefs, and other characteristic adaptations. This conceptualization provides a new framework for studying personality and culture at three levels. Transcultural research focuses on identifying human universals, such as trait structure and development; intracultural studies examine the unique expression of traits in specific cultures; and intercultural research characterizes cultures and their subgroups in terms of mean levels of personality traits and seeks associations between cultural variables and aggregate personality traits. As an example of the problems and possibilities of intercultural analyses, data on mean levels of Revised NEO Personality Inventory scales from college age and adult samples (N = 23,031) of men and women from 26 cultures are examined. Results showed that age and gender differences resembled those found in American samples; different subsamples from each culture showed similar levels of personality traits: intercultural factor analysis yielded a close approximation to the Five-Factor Model; and factor scores were meaningfully related to other culture-level variables. However, mean trait levels were not apparent to expert raters, casting doubt on the accuracy of national stereotypes. Trait psychology can serve as a useful complement to cultural perspectives on human nature and personality. PMID- 11767821 TI - Lexical studies of indigenous personality factors: premises, products, and prospects. AB - The rationale for lexical studies rests on the assumption that the most meaningful personality attributes tend to become encoded in language as single word descriptors. We articulate some key premises of the lexical approach and then review a number of studies that have been conducted examining the factor structure of personality descriptors extracted from dictionaries. We compare lexical studies in English and 12 other languages, with attention to delineating consistencies between the structures found in diverse languages. Our review suggests that the Anglo-Germanic Big Five is reproduced better in some languages than in others. We propose some organizing rules for lexical factor structures that may be more generalizable than the contemporary Big-Five model. And, we propose several candidate structural models that should be compared with the Big Five in future studies, including structures with one, two, and three very broad factors, an alternative five-factor structure identified in Italian and Hungarian studies, and a seven-factor structure represented in Hebrew and Philippine studies. We recommend that in future studies more attention be paid to middle level personality constructs and to examining the effects of methodological variations on the resulting factor structures. PMID- 11767822 TI - Self as cultural product: an examination of East Asian and North American selves. AB - In the past decade a wealth of research has been conducted on the cultural foundation of the self-concept, particularly with respect to East Asian and North American selves. The present paper discusses how the self differs across these two cultural contexts, particularly with respect to an emphasis on consistency versus flexibility, an intraindividual versus an extraindividual focus, the malleability of the self versus world, the relation of self to others, and self enhancing versus self-critical motivations. These differences reveal the manifold ways that culture shapes the self. PMID- 11767823 TI - Individualism-collectivism and personality. AB - This paper provides a review of the main findings concerning the relationship between the cultural syndromes of individualism and collectivism and personality. People in collectivist cultures, compared to people in individualist cultures, are likely to define themselves as aspects of groups, to give priority to in group goals, to focus on context more than the content in making attributions and in communicating, to pay less attention to internal than to external processes as determinants of social behavior, to define most relationships with ingroup members as communal, to make more situational attributions, and tend to be self effacing. PMID- 11767824 TI - Indigenization and beyond: methodological relationalism in the study of personality across cultural traditions. AB - A brief intellectual history of the indigenization movement in Asia leads to the thesis that the generation of psychological knowledge is culture dependent. Indigenous psychologies go further and insist on viewing a target group from the natives' own standpoint. Psychological decentering underlies conceptions of human existence rooted in Asian intellectual traditions, in particular, relatedness between persons predominates in Confucianism. These conceptions demand new approaches to knowledge generation that signify a paradigmatic shift from methodological individualism to methodological relationalism. An implication is that relationships precede situations in the study of personality and social behavior. We define personality as the sum total of common attributes manifest in, and abstracted from, a person's behavior directly or indirectly observed across interpersonal relationships and situations over time. We rely on the notion that there are identifiable levels of cognition to develop a metatheoretical framework for reconstructing selfhood. Confronting the subject object dichotomy opens the door to investigations of transcendent consciousness; confronting the self-other demarcation underlying Western theories leads to the construction of self-in-relations. PMID- 11767825 TI - Human nature and culture: an evolutionary psychological perspective. AB - Personality psychology is the broadest of all psychological subdisciplines in that it seeks a conceptually integrated understanding of both human nature and important individual differences. Cultural differences pose a unique set of problems for any comprehensive theory of personality-how can they be reconciled with universals of human nature on the one hand and within-cultural variation on the other? Evolutionary psychology provides one set of conceptual tools by which this conceptual integration can be made. It requires jettisoning the false but still-pervasive dichotomy of culture versus biology, acknowledging a universal human nature, and recognizing that the human mind contains many complex psychological mechanisms that are selectively activated, depending on cultural contexts. Culture rests on a foundation of evolved psychological mechanisms and cannot be understood without those mechanisms. PMID- 11767826 TI - Personality measurement in cross-cultural perspective. AB - I first provide an overview of general issues in personality measurement across cultures (e.g., measurement bias and equivalence, levels of test adaptation or indigenization). Then, in keeping with the organization of this special issue, I discuss personality measurement from alternative theoretical perspectives that have addressed, in varying degrees, personality and its measurement in cross cultural perspective (i.e., trait perspectives, projective techniques, cultural psychology and constructivist perspectives, evolutionary perspectives). An integrated measurement approach is advocated, incorporating diverse aspects or levels of personality, while drawing on the complementary strengths of alternative approaches. PMID- 11767827 TI - Preparation, spectral behaviour and oxidation of some new zinc(II) salicylaldimines containing sterically hindered phenol. AB - A series of new bis[N-(2,6-di-tert-butyl-1-hyxyphenyl)salicylideneminato]zinc(II) complexes bearing one or two HO- and CH3O-substituents on the salicylaldehyde moiety were prepared, and their spectroscopic properties (IR, electronic, 1H NMR) as well as the ESR spectra of the one-electron oxidation products were examined. The 1H NMR examination of Zn(Lx)2 indicates that, contrary to expectations, the proton resonances of the complexes are shifted to the high-field side compared with those of the free ligands. Oxidation of these compounds with PbO2 results in the formation of mono- and biradical types Zn(II)-stabilized phenoxyls in which there are both anisotropic and alternating line-width trends. Some spectral patterns are typical for weak interacting (J << A) or the case of J approximately A biradicals, in which ESR signal appeared as superimposition of two non interacting monoradical centers with S = 1/2. ESR studies on biradicals type of Zn(L*x)2 at 300 and 77 K did not show any evidence of strong exchange coupling in these systems. All radical species were characterized by the ESR parameters. PMID- 11767828 TI - EPR and optical absorption studies of VO2+ doped L-arginine phosphate monohydrate single crystals--part I. AB - The electron paramagnetic resonance (EPR) studies on VO2+ doped L-arginine phosphate monohydrate (LAP) single crystals at room temperature at X-band frequencies reveal the presence of two magnetically inequivalent VO2+ sites occupying interstitial positions in the lattice with fixed orientations and show very high angular dependence. The principal values of the g and A tensors indicate that the electrostatic field around the VO2+ ion is rhombic. The optical absorption spectra at room temperature show four absorption bands at 16155, 14775, 10928 and 10526 cm(-1), characteristic of rhombic symmetry. From EPR and optical absorption data, the molecular orbital bonding coefficients (beta2, epsilon2, P and k) and the crystal field parameters have been evaluated. PMID- 11767829 TI - Quenching effect of triethylamine on peroxyoxalate chemiluminescence in the presence of 7-amino-4-trifluoromethylcumarin. AB - The quenching effect of triethylamine on strong chemiluminescence of bis-(2,4,6 trichlorophenyl)oxalate-hydrogen peroxide system in the presence of 7-amino-4 trifluoromethylcumarin was studied. The system resulted in a nice Stern-Volmer plot with a kQ value of 1.07 x 10(-3) M(-1), in the quencher concentration range of 1.52 x 10(-4) - 1.36 x 10(-3) M. The linear correlation between the decay rate constant of the resulting chemiluminescence and the quencher concentration was also investigated. PMID- 11767830 TI - Thermodynamics of substituted pyrazolone IX: potentiometric, spectrophotometric and conductometeric studies of 4-(4-chlorophenylazo)-3-methyl-1-[2-hydroxy-3 morphilinopropane 1-yl]-2-pyrazolin-5-one and its metal complexes. AB - The dissociation constants of 4-(4-chlorophenylazo)-3-methyl-1-[2-hydroxy-3 morphilinopropane-1-yl]-2-pyrazolin-5-one (CAMP) has been determined potentiometrically in 0.1 M KCl and 40% (v/v) ethanol-water mixture. The stepwise stability constants of the formed complexes of Mn2+, Co2+, Ni2+, Cu2+, Zn2+, La3+, Ce3+ and UO(2)2+, with CAMP have been determined. The stability of the formed complexes were found as follows: UO(2)2+ > Ce3+ > La3+ > Mn2+ < Co2+ < Ni2+ < Cu+ > Zn2+. The thermodynamic parameters (deltaG, deltaH and deltaS) for CAMP and its complexes were evaluated and discussed. The dissociation process is non-spontaneous, endothermic and entropically unfavourable. The formation of the complexes have been found to be spontaneous, exothermic or endothermic (depending on the metal) and entropically favourable. The stoichiometries of these complexes were determined spectrophotometrically and conductometrically and indicated the formation of 1:1 and 1:2 (metal:ligand) complexes. PMID- 11767831 TI - Thermal properties and optical transition probabilities of Tm3 + doped TeO2-WO3 glass. AB - Glasses with the composition of (1 - x)TeO2 + (x)WO3, where x = 0.15, 0.25 and 0.3 were prepared and, their thermal and absorption measurements were carried out. Differential thermal analysis (DTA) curves taken in the 23-600 degrees C temperature range with a heating rate of 10 degrees C/min reveal a change in the value of the glass transition temperature, Tg, while crystallization was not observed for the glasses containing a WO3 content of more than 15 mol%. All the glasses were found to be moisture-resistant. The absorption bands corresponding to the absorption of the 1G4, 3F2, 3F3 and 3F4, 3H5 and 3H4 levels from the 3H6 ground level of the Tm3+ ion were observed in the optical absorption spectra. Integrated absorption cross-sections of each band except that of 3H5 level was found to vary with the glass composition. Judd-Ofelt analysis was carried out for the samples doped with 1.0 mol% Tm2O3. The omega2 parameter shows the strongest dependence on the host composition and it increases with the increasing WO3 amount. The value of omega4 increases rather slowly while the value of omega6 is practically independent of the composition. The strong dependence of the parameter omega2 indicates that this parameter is related to the structural change and the symmetry of the local environment of the Tm3+ ions in this glass. PMID- 11767832 TI - Ab initio calculations, FTIR and raman spectra of 2,3-difluorobenzonitrile. AB - Geometry, vibrational frequencies, atomic charges and several thermodynamic parameters (the total energy, the zero point energy, the rotational constants and the room temperature entropy) were calculated using ab initio quantum chemical methods for 2,3-difluorobenzonitrile molecule. The results were compared with experimental values. With the help of two specific scaling procedures, observed FTIR and Raman vibrational frequencies were analysed and assigned to different normal modes of the molecule. The error obtained was in general very low. Other general conclusions have also been deduced. PMID- 11767833 TI - Infrared spectra of the hydrogen bond in pimelic acid crystals: polarization and temperature effects. AB - This paper deals with the polarized IR spectra of the hydrogen bond in pimelic acid crystals and their quantitative interpretation. The spectra were measured for the vO-H and vO-D band frequency regions, at temperatures of 298 and 77 K, for the 'alpha' crystalline form of pimelic acid. Two kinds of transmission spectra were obtained, for the beam perpendicular to the two different crystalline faces: 'ac' and 'ab'. The spectra of the hydrogen and the deuterium bonded systems were quantitatively reproduced, with sufficient accuracy, on the basis of the 'strong-coupling' model, assuming the (COOH)2 cycles to be the structural units responsible for the basic spectral properties. It was found that the spectra could be reproduced only, when assuming spectral activity in the IR of the totally symmetric proton stretching vibrations in centrosymmetric cyclic dimers of hydrogen bonds. The polarization effects in the crystal spectra were interpreted as directly connected with the hydrogen bond orientation in the crystal. However, in the pimelic acid crystalline spectra there were not observed another polarization effects characteristic for another carboxylic acid crystals, depending on differentiation of the long- and of the short-wave branch properties of each of the vO-H and vO-D bands. The temperature variation only affect the intensity ratio between the lower- and the higher-frequency branches of the vO-H and vO-D bands. These spectral effects were ascribed to less strained hydrogen bond structures in the pimelic acid lattices of the alpha' crystalline form and a relatively low concentration of defects in the lattices. PMID- 11767834 TI - A spectrofluorimetric method for cysteine and glutathione using the fluorescence system of Zn(II)-8-hydroxyquinoline-5-sulphonic acid complex. AB - The addition of thiol compounds to the fluorescence system of Zn(II)-8 hydroxyquinoline-5-sulphonic acid complex (Zn(II)-HQS) in H3BO3-Na2B4O7 buffer (pH 8.50) solution led to immediate fluorescence inhibition, which was proportional to their amounts. Based on this finding, a novel spectrofluorimetric method for the determination of cysteine (Cys) and reduced glutathione (GSH) has been developed. The detection limits were 17 ng ml(-1) and 0.6 microg ml(-1), respectively. Most amino acids had no interference at high concentrations. The proposed method has been applied to the determination of Cys in protein hydrolysate and cystine electrolyte, and GSH in human blood serum with recoveries of 95.6-104.5%. PMID- 11767835 TI - Room temperature solution studies of complexation between o-chloranil and a series of anilines by spectrophotometric method. AB - Electron donor-acceptor (EDA) complex formation between o-chloranil and a series of anilines has been studied in CCl4 medium. In all the cases, EDA complexes are formed instantaneously on mixing the donor and acceptor solutions. N,N dimethylaniline and N,N-dimethyl-p-toluidine form stable EDA complexes with o chloranil while the other complexes decay slowly into secondary products. The kinetics of all these reactions has been studied by UV-VIS absorption spectrophotometric method and the rate constants of the reactions and formation constants of the EDA complexes have been determined. The charge transfer (CT) transition energies of the complexes are found to change systematically with change in the number and position of the methyl groups in the donor molecules (methylanilines). From an analysis of this variation, the electron affinity of o chloranil has been found to be 2.54 eV. A perturbational inductive effect Huckel parameter hMe has been found from this trend and the value obtained (-0.27) is very close to that (-0.3) obtained by Lepley (J. Am. Chem. Soc., 86 (1964) 2545) from a study of tetracyano ethylene (TCNE)-methylbenzene complexes. PMID- 11767836 TI - Vibrational frequencies and structural determinations of 1,4-thioxane. AB - We present a detailed analysis of the structure and infrared spectra of 1,4 thioxane. The vibrational frequencies of the 1,4-thioxane molecule were analyzed using standard quantum chemical techniques. Frequencies were calculated at the MP2 and DFT levels of theory using the standard 6-31G* basis set. The structural transformation of the chemical agent bis (2-chloroethyl) sulfide (HD, mustard gas) and the related symmetry to a previously study compound(4) makes the symmetry of the 1,4-thioxane molecule an interesting candidate for study. The molecule exists normally in a Cs configuration similar to the chair form of cyclohexane. High-energy forms of 1,4-thioxane with C1 and C2 symmetry also exist. PMID- 11767837 TI - An ab initio study of electronic structure and spectra of 8-bromoguanine: a comparative study with guanine. AB - Ground state geometries of the four tautomeric forms keto-N9H, keto-N7H, enol-N9H and enol-N7H of 8-bromoguanine (8BG) were optimized using the ab initio RHF procedure employing a mixed basis set consisting of the 6-311 + G* basis set for the nitrogen atom of the amino group and the bromine atom, and the 4-31G basis set for all other atoms. These calculations were followed by correlation correction of the total energy at the MP2 level using the same basis set. The different tautomeric forms of 8BG in the ground state were solvated using the isodensity surface polarized continuum model (IPCM) of the SCRF theory both at the RHF and MP2 levels. Excited states were generated employing configuration interaction among singly excited configurations (CIS) obtained using a limited window of filled and empty molecular orbitals. Formation of hydrogen-bonded complexes between 8BG and three water molecules in the ground and excited states was considered in order to account for solvent effects approximately. Excited state geometry was optimized in each case for the lowest singlet excited state which was found to be of pi-pi* type. Vibrational frequency analysis was performed in order to ensure that the stationary points located on the potential energy surfaces by geometry optimization were minima. It is found that 8BG would occur in the ground state dominantly in the keto-N7H form both at the aqueous solution-air interface and inside the bulk liquid. The observed absorption and fluorescence spectra of 8BG can be explained satisfactorily considering only the keto-N7H form of the molecule. The enol tautomers of 8BG do not appear to be important from the point of view of ground state properties or electronic spectra. The observed differences between the behaviors of guanine and 8BG can be easily explained on the basis of the results obtained. PMID- 11767838 TI - Solvent effects on the absorption and fluorescence characteristics of tin(IV) mesoporphyrin. AB - The absorption and fluorescence characteristics of tin(IV) mesoporphyrin (SnMP) and its analog tin(IV) protoporphyrin (SnPP) were studied in a series of organic solvents. Fluorescence quantum yields were calculated using the Strickler-Berg equation. Good correlation was found between calculated values and measured relative values. Fluorescence lifetime, radiative lifetime and non-radiative lifetime were also calculated. The parameters showed variation depending on ligation as well as H-bonding. Unusual long lifetime and high quantum yields were found in alcohol solvents. This finding might contribute to elucidation of the nature of tin porphyrins to inhibit heme oxygenase. PMID- 11767839 TI - Ab initio study of the vibrational spectra of the hydrogen-bonded nitric acid dimer. AB - The changes in the vibrational characteristics characterizing the dimerization of nitric acid have been investigated by ab initio calculations at the MP2 level, with 6-31G(d,p) and 6-31 + G(d,p) basis sets, and B3LYP/6-31G(d,p) calculations. The most consistent agreement between the computed values of the frequency shifts for the planar fully symmetric structure (2A) and those experimentally observed suggests that this structure is preferred. It was established that the most sensitive to the complexation is the stretching O-H vibration. The values of the frequency shift (-306 cm(-1)) is indicative for the formation of the relatively strong hydrogen bonds. The calculations predict an increase of the infrared intensity of the stretching O-H vibration in the nitric acid dimer more than 26 times. PMID- 11767840 TI - Theoretical prediction of A(3)0+ <-- X(1)0+ and B(3)1 <-- X(1)0+ spectra of the Zn-rare gas van der Waal's molecules. AB - Excitation spectra arising from A(3)0+ <-- X(1)0+ and B(3)1 <-- X(1)0+ electronic transitions in the Zn-rare gas (RG) van der Waal's molecules are calculated using the newly obtained ab initio potential curves for these species. The radial Schrodinger equation for nuclear motion was solved numerically with the calculated potentials to evaluate the corresponding vibrational levels and radial wavefunctions for the ground X(1)0+ and excited A(3)0+ and B(3)1 states of the Zn RG complexes. The wavefunctions have been subsequently used in the calculation of the appropriate Franck-Condon factors to yield information on relative intensities of the vibrational bands produced by A(3)0+ <-- X(1)0+ and B(3)1 <-- X(1)0+ transitions. PMID- 11767841 TI - Structural chemistry of polycyclic heteroaromatic compounds. Part 13. Photoelectron spectra and electronic structures of tricyclic hetarenes of the anthracene type. AB - The ultraviolet photoelectron spectra of two tricyclic heteroaromatic compounds (2,3) that are pi-isoelectronic with anthracene (1) have been recorded and analysed making use of semi-empirical AM1 and PM3, as well as density functional theory (DFT) B3LYP calculations. In compounds 2 and 3, one peripheral benzene ring of compound 1 is substituted by a thiophene ring that is either [b]- or [c] annellated. In compounds 2 and 3, only small shifts are found for most of the ionization potentials of pi electrons. Since the ionization energies of all occupied pi molecular orbitals of compounds 1-3 could be assigned, a direct comparison of their pi electron energy is possible. Compared with compound 1, the pi-electron system of naphtho[2,3-b]thiophene (2) is stabilized by 0.6 eV, while that of naphtho[2,3-c]thiophene (3) is destabilized by 0.2 eV. [b]-Annellation of the thiophene ring is thus favourable while [c]-annellation is unfavourable. PMID- 11767842 TI - Vibrational spectra and normal coordinate analysis of a weak ligand complex, Co(p DMABA)2Cl2 x 2H2O. AB - The complex Co(p-DMABA)2Cl2 x 2H2O (p-dimethylaminobenzaldehyde, p-DMABA) was prepared from the solid-state reaction of a weak ligand p-DMABA and CoCl2 x 6H2O at lower heating temperature (60 degrees C). It is very difficult to obtain the title complex using solution reaction method, less than isolating single crystals. In order to determine the crystal structure of the title compound, we have to rely on the X-ray powder diffraction data. That is, the crystal structure can be solved directly from powder data, which crucial step is to constitute the structure model. Indirect spectroscopic methods, such as infrared and Raman spectroscopes, and further vibrational assignments made with the aid of normal coordinate calculations by using a modified Urey-Bradley force field, were analyzed to proposed molecular structure. One hundred and fifty-seven internal coordinates were established and 129 theoretical vibrational frequencies were calculated. An appropriate set of internal coordinates and force constants in the course of calculation were introduced, so that the calculated vibration frequencies are good agreement with the observed values. The average difference and the maximum deviation between theoretic and experimental frequencies are 2.44 and 8.0 cm(-1), respectively. Thus the normal coordinate analysis is a powerful tool to the molecular structure. Other structural and spectral properties are also discussed in this paper. The purpose of the present paper is to obtain a good structural model. This model was used as starting model for crystal structure determination from powder X-ray diffraction (XRD) data. PMID- 11767843 TI - Fourier transform infrared spectroscopic study of surface acidity by pyridine adsorption on Mo/ZrO2-SiO2(Al2O3) catalysts. AB - Acidity of the oxidic molybdenum catalysts supported on mixed ZrO2-SiO2 and ZrO2 Al2O3 carriers was investigated by Fourier transform infrared spectroscopy of pyridine adsorption. Deposition of molybdenum on ZrO2-SiO2 and ZrO2-Al2O3 supports leads to formation of surface Bronsted acid sites. The number of the Bronsted and Lewis acid sites in supported-molybdenum catalysts depends on both the ZrO2 content and the type of the support. With increasing ZrO2 content, the Lewis acid sites increase for both series of catalysts. The Bronsted acid sites are higher for Mo/ZrO2-SiO2 samples compared to those for Mo/ZrO2-Al2O3 and also increase with zirconia. PMID- 11767844 TI - Spectrophotometric kinetic and determination of quinones and barbiturates. AB - The kinetics of 1,3-dimethylbarbituric acid with some quinones, namely 1,4 benzoquinone, 1,4-naphthoquinone and p-chloranil in 50% methyl alcohol-water mixture have been investigated spectrophotometrically at 30-50 degrees C. The reaction follows overall second-order kinetics, first order each in reactant. From the dependence of the rate constants on temperature, activation parameters have been calculated. A plot of deltaH# versus deltaS# for the reaction gave a good straight line with an isokinetic temperature of 387.66 K. The rate of reaction increases with increasing dielectric constant of the medium. Based on this reaction, a spectrophotometric determination method of quinones is described. Beer's law was obeyed within the concentration range 2.7-61.5 microg ml(-1) quinone. The method was applied for determination of barbituric, thiobarbituric and 1,3-dimethylbarbituric acids with 1,4-naphthoquinone within a concentration range of 3.2-39.5 microg ml(-1) barbiturate. The reaction mechanism and reactivity have been discussed. PMID- 11767845 TI - Neutron scattering, infra red, Raman spectroscopy and ab initio study of L threonine. AB - Inelastic incoherent neutron scattering spectra (IINS) were obtained for normal and deuterated L-threonine. Raman and infrared spectra were also recorded. Geometries were optimized for the zwitterion form using ab initio Hartree-Fock (HF) levels with 6-31G*, 6-311G*, 6-311G** and 6-311 + + G** basis sets. Force fields and normal modes were calculated and used as basis for an assignment of the spectral features. PMID- 11767846 TI - On the structure of human hair melanins from an infrared spectroscopy analysis of their interactions with Cu2+ ions. AB - Melanins were isolated from dark and red human hair and complexed with copper ions at various pH values in a complexing medium. IR spectra of melanins and their Cu2+-complexes for pellets with KBr were obtained. The IR spectra indicate that Cu2+ ions bound to melanins are fixed by different carboxyl and hydroxyl (phenolic and/or alcoholic) groups in the macromolecule. From these results it is concluded that, generally, melanin carboxyl groups are responsible for interactions of metal ions with the melanin molecule. Complexes of melanins isolated from dark and red human hair show structural differences when analysed by IR spectroscopy. Conclusions from these investigations assist in the differentiation of structures of analysed hair melanins. IR spectral analysis of melanin samples and their complexes suggest that melanin samples obtained from red hair may contain eumelanin. PMID- 11767847 TI - Fluorescence studies on native and bound to trifluraline soy bean Lb"a" in the enhanced N2 fixation. AB - The differences in the tryptophan (Trp) fluorescence of native (control) Lb"a" and experimental substance isolated from nodules of the Williams' soy beans variety treated with trifluraline at a concentration of 2.1 x 10(-10) M have been studied. A positively charged environment has been proved for the tryptophans of the native Lb"a" and a negative one for the tryptophans of the experimental Lb"a". The difference in the tryptophan emission spectra at lambdaex = 280 and 300 nm may be assigned to conformational alterations occurring in the experimental Lb"a". This is also confirmed by the greater energy transfer from tyrosine to tryptophan in the experimental Lb"a"--30% compared to the 10% in the native Lb"a". The value of the constant of acrylamide quenching (Ksv = 2.77 M( 1)) shows that the tryptophans are buried more deeply in the experimental Lb"a" than in the native Lb"a" (Ksv = 4 M(-1)). They are substantially lower than Ksv of the standard compound N-Ac-Trp-NH2 (16.30 M(-1)). The activation energy (Ea) of the thermal quenching of tryptophan fluorescence is higher for the experimental Lb"a" (37 kJ mol(-1)) as compared to the standard compound N-Ac-Trp NH2 (24 kJ mol(-1)) and the native Lb "a" (32 kJ mol(-1)). The dissociation constant of the complex of trifluraline with Lb "a" (6.32 x 10(-11) M) has been determined as well as the stoichiometric ratio trifluraline/Lb"a" (1:1). The estimated nitrogenase activity (microM/gfrw h) and the total Lb (mg/gfrw) for trifluraline are higher as compared to those for the control. PMID- 11767848 TI - How much does it cost? PMID- 11767849 TI - A question of care... PMID- 11767850 TI - A question of care... PMID- 11767851 TI - A question of care... PMID- 11767852 TI - A question of care... PMID- 11767853 TI - Betel quid chewing. PMID- 11767854 TI - Acupuncture for controlling gag reflex? PMID- 11767855 TI - Orthodontics and occlusion. AB - The discipline of orthodontics is directed towards alteration of the occlusion of the teeth and the relationships of the jaws. It is therefore somewhat surprising to find that there is little scientific evidence to support any of the concepts that suggest occlusal goals for orthodontic treatment. Most of the current concepts of orthodontic treatment are based upon personal opinion and retrospective studies. Nevertheless, an attempt is made here to provide a guide to the relationship of orthodontics and the occlusion that is evidence based. Where the evidence is weak, these areas have been highlighted. PMID- 11767856 TI - Out-of-hours emergency dental services--development of one possible local solution. AB - This paper describes the development of a local solution to the problem of the provision of out-of-hours dental care in Newcastle and North Tyneside in the north east of England. Focus groups were used to review the current provision of, and problems with, dental out-of-hours emergency provision. A consensus conference involving both general dental and medical practitioners, was subsequently used to develop possible alternative methods for the provision of out-of-hours emergency dental services. A centralised service delivered from a secure location in conjunction with general medical practitioners was developed which was dependent on a nurse-led triage. The linkage with NHS Direct may be an opportunity, in some locations, to integrate dental services more fully with other out-of-hours primary care services. The method described allowed a solution to be generated by practitioners themselves, thus giving ownership and acceptance to the chosen option. PMID- 11767857 TI - Vertical-split fracture of mandibular condyle and its sequelae. AB - A case of vertical-split fracture of the right mandibular condyle and its sequelae is presented. The patient was a 16-year-old female being assessed for orthodontic treatment. Orthopantomograph and plain joint view radiographs showed a remodelled condyle which had suffered trauma 10 years previously. This type of fracture is unusual in nature but has not led to any secondary lack of growth, restriction of movement or facial asymmetry. PMID- 11767858 TI - The use of QLF to quantify in vitro whitening in a product testing model. AB - BACKGROUND: Professional and consumer interest in whitening products continues to increase against a background of both increased oral health awareness and demand for cosmetic procedures. In the current legal climate, few dentists are providing 'in-office' whitening treatments, and thus many patients turn to home-use products. The most common of these are the whitening toothpastes. Researchers are keen to quantify the effectiveness of such products through clinically relevant trials. AIM: Previous studies examining whitening products have employed a variety of stained substrates to monitor stain removal. This study aimed to quantify the removal of stain from human enamel using a new device, quantitative light-induced fluorescence (QLF). The experimental design follows that of a product-testing model. MATERIALS AND METHODS: A total of 11 previously extracted molar teeth were coated with transparent nail varnish leaving an exposed window of enamel. The sound, exposed enamel was subject to a staining regime of human saliva, chlorhexidine and tea. Each of the eleven teeth was subjected to serial exposures of a positive control (Bocasan), a negative control (water) and a test product (Yotuel toothpaste). Following each two-minute exposure QLF images of the teeth were taken (a total of 5 applications). Following completion of one test solution, the teeth were cleaned, re-stained and the procedure repeated with the next solution. QLF images were stored on a PC and analysed by a blinded single examiner. The deltaQ value at 5% threshold was reported. ANOVA and paired t-tests were used to analyse the data. RESULTS: The study confirmed the ability of QLF to longitudinally quantify stain reduction from human enamel. The reliability of the technique in relation to positive and negative test controls was proven. The positive control had a significantly (alpha = 0.05) higher stain removal efficacy than water (p = 0.023) and Yotuel (p = 0.046). Yotuel was more effective than water (p = 0.023). CONCLUSION: The research community, the practicing clinician and the consumer all require sound product evaluation data. The use of human enamel specimens may offer more relevant clinical data. QLF has been designed as an in vivo device. Further development of the technique should permit in vivo clinical whitening trials. PMID- 11767860 TI - Ethics--dentistry and tooth-drawing in the late eighteenth and early nineteenth centuries in England. Evidence of provision at all levels of society. AB - The popularity of caricature at the end of the eighteenth century allows a researcher to observe the social as well as the technical side of dentistry as it was then available throughout the kingdom. The value of these caricatures is further enhanced by the unconscious inclusion of everyday objects which a narrative account would not think it worthwhile including, even if such narrative account had existed. PMID- 11767859 TI - Periodontal health of London women during early pregnancy. AB - OBJECTIVES: A descriptive cross-sectional study to determine the severity of periodontal disease in early pregnancy and its relation to demographic variables in a South East London population. METHODS: 2,027 pregnant women attending Guy's Hospital for an ultrasound scan at 10 to 14 weeks gestation were assessed. Data were collected via questionnaire and periodontal examination, including plaque and bleeding scores, pocket probing depth and loss of attachment. RESULTS: Mean age was 29.8 years (sd 5.5). Of these, 61.8% were white, 28.5% black, and 9.7% of other ethnic group. A total of 15% reported smoking during pregnancy. The mean number of teeth present was 28 (sd 2) per subject, mean percentage of sites with plaque present was 60.5% (sd 22.6), mean pocket depth was 2.0 mm (sd 0.4), mean loss of attachment was 0.4 mm (sd 0.3), and the mean percentage of sites bleeding on probing was 20.2% (sd 16.3). Linear regression demonstrated that probing depth was related to age, ethnicity, socioeconomic status and plaque score but not to smoking whereas loss of attachment demonstrated relationships with age, smoking status and plaque score but not ethnicity or socioeconomic status. CONCLUSION: There was a relatively high proportion of subjects with deep periodontal pockets in this pregnant population compared to the Adult Dental Health Survey 1998 but with similar levels of loss of attachment and percentage of sites with plaque present. Several demographic factors were associated with the level of periodontal disease in this population. PMID- 11767861 TI - Focus Awards 2001. PMID- 11767862 TI - Management of tracheobronchial stenosis: is there an enlightened path? PMID- 11767863 TI - Management of chronic obstructive pulmonary disease in the twenty-first century. PMID- 11767864 TI - Bronchoscopic dilatation in the management of benign (non-transplant) tracheobronchial stenosis. AB - BACKGROUND: Tracheobronchial stenosis in the adult patient is a recognized postoperative complication of sleeve resection or lung transplantation, but also occurs in medical conditions such as sarcoidosis, tuberculosis, postintubation/tracheostomy or post-radiation. AIMS: To assess the response of bronchoscopic dilatation in the management of benign (non-transplant) tracheobronchial stenosis and the longevity of symptomatic relief. METHODS: Eight patients underwent bronchoscopic dilatation for benign (non-transplant) tracheobronchial stenosis. The indications were post-tuberculous bronchostenosis (n = 3), post-tracheostomy/endotracheal intubation strictures (n = 3), postradiation bronchostenosis (n = 1) and narrowing of the tracheal lumen following a muscle flap surgery for tracheoesophageal fistula (n = 1). RESULTS: Dilatation alone was effective in the management of four patients (50%). Two patients had stent placement postdilatation, one patient had tracheal resection and primary anastomosis and one patient had laser ablation for restenosis followed by balloon dilatation. All patients had clinical improvement. One patient was successfully weaned off mechanical ventilation and extubated. There was no procedure-related mortality and all patients were alive and well at the time of reporting, with a mean duration since procedure of 123 +/- 105 (range 8 340) weeks. The complications observed were granuloma formation at the site of laser excision and restenosis, each in one patient. CONCLUSIONS: Bronchoscopic dilatation is a safe and effective modality in the initial assessment and management of benign tracheobronchial stenosis. Stent placement and Nd:YAG laser therapy complement a dilatation procedure in the combined bronchoscopic treatment of benign tracheobronchial stenosis. PMID- 11767865 TI - Hepatocellular carcinoma and chemoembolization. AB - BACKGROUND: Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting. AIMS: To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria. METHODS: Selective catheterization of the right or left hepatic arteries was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1-3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival. RESULTS: CT response rates: partial response 19% (n = 7), median duration 11 months (range 2+ to 37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+); stable disease 42% (n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% (n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0-37+). Median overall survival was 15 months (range 6-50+). CONCLUSION: Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour. PMID- 11767866 TI - Role of the observed long case in postgraduate medical training. AB - BACKGROUND: The teaching of long case examination technique emphasizes case presentation, problem identification and discussion of management. It assumes that history taking and ability to perform a complete physical examination in a limited time are adequate. These can only be assessed by directly observing the long case examination. AIMS: To explore the usefulness of observing long case performance. METHODS: We used a structured assessment form to observe and evaluate the overall long case performance of 19 doctors in our physicians' training programme. Nine, group A, had received 6 months training, whereas the 10 in group B had only just commenced clinical examination training. RESULTS: Ten (53%) passed their long case, seven from group A and three from group B. Thirteen (68%) passed the history and examination section. Three failed the history component and five failed the examination component. The groups had similar scores for observed history taking. Common problems included poor time management, excessive time required to take the history and lack of organization of questions. Physical examination was usually poorly organized, requiring the use of short cuts, particularly in the respiratory, musculoskeletal and neurological systems. Group A were better at presentation and discussion, with eight (89%) passing compared with four (40%) passing in group B. CONCLUSION: These results reflect the emphasis in our training programme on long case discussion and management, rather than examination technique. The observed case allowed for detection of defects in history-taking skills and time management. Therefore, it is valuable in preparing candidates for their Fellowship examinations. PMID- 11767868 TI - Improving clinical practice: what works and what doesn't? PMID- 11767867 TI - Improving benzodiazepine prescribing for elderly hospital inpatients using audit and multidisciplinary feedback. AB - BACKGROUND: Benzodiazepines are commonly prescribed for older people. Inappropriate benzodiazepine prescribing may result in serious adverse effects, including confusion and falls. AIMS: To determine the prevalence and appropriateness of benzodiazepine prescribing for elderly inpatients at nine public hospitals in Victoria, Australia, and to assess the impact of multidisciplinary feedback on quality of benzodiazepine prescribing. METHODS: Clearance for the study was obtained from ethics committees of participating hospitals. Medication charts for 1301 patients aged 65 years and over were reviewed to identify patients prescribed a benzodiazepine. Using an evidence based indicator of prescribing appropriateness, cross-sectional notes-based audits were conducted at three time points (baseline, 4-8 weeks and 6 months). Feedback of baseline audit results was provided to medical, pharmacy and nursing staff at multidisciplinary meetings. Changes in benzodiazepine prescribing over the following 6 months were assessed. RESULTS: At baseline, benzodiazepines were prescribed for 36% of patients, and 20% of prescriptions were appropriate. Four to six weeks after feedback, the proportion of patients prescribed a benzodiazepine had not changed significantly (31%, P = 0.125); however, more prescriptions were appropriate (44%, P < 0.0001). For patients who were using a benzodiazepine prior to admission and had a contraindication, there were more attempts to withdraw or reduce the dose (47% vs 21%, P = 0.002) and more prescriptions were for acceptable indications (7.4% vs 2.6%, P = 0.024). Six months after feedback, appropriateness of prescribing remained improved compared with baseline (50%, P = 0.002). CONCLUSIONS: Benzodiazepines were prescribed for approximately one in three elderly hospital inpatients and a large proportion was inappropriate. A multidisciplinary intervention based on audit and feedback improved prescribing and the impact of the intervention was still evident after 6 months. PMID- 11767869 TI - Discrimination in medicine: the uncertain role of values. PMID- 11767870 TI - Myocardial perfusion imaging in evaluation of undiagnosed acute chest pain. AB - Myocardial perfusion imaging is a relatively new technique in the emergency department management of acute chest pain. With improved sensitivity and specificity compared to traditional methods of risk stratification, an abnormal scan rapidly identifies individuals with acute perfusion abnormalities and allows the appropriate utilization of limited resources. Conversely, a normal scan allows prompt hospital discharge and is associated with excellent outcomes both in the short and medium terms. Acute chest pain myocardial perfusion imaging has been demonstrated to alter patient management and disposition and its routine use results in decreased costs in the intermediate risk population. PMID- 11767871 TI - Sentinel lymph node biopsy in patients with melanoma and breast cancer. AB - Sentinel lymph node biopsy (SNLB) is a new method for staging regional node fields in patients with cancers that have a propensity to metastasise to lymph nodes. The majority of early experience has been obtained in patients with melanoma and breast cancer. The technique requires the close cooperation of nuclear medicine physicians, surgical oncologists and histopathologists to achieve the desired accuracy. It involves: (i) identification of all lymph nodes that directly drain a primary tumour site (the sentinel nodes) by the use of pre operative lymphoscintigraphy, (ii) selective excision of these nodes by the surgeon, guided by pre-operative blue dye injection and a gamma detecting probe intra-operatively and (iii) careful histological examination of the sentinel nodes by the histopathologist using serial sections and immunohistochemical stains. If the nodes are normal it can be inferred with a high degree of accuracy that all nodes in the node field are normal. This means that radical dissections of draining node fields can be avoided in patients with normal lymph nodes. A further advantage of lyamphatic mapping is that drainage to sentinel nodes in unusual locations is identified, leading to more accurate nodal staging than could be achieved with routine dissection of the closest node field. PMID- 11767872 TI - Ars gratia artis and the morganatic marriage: 'Let us not to the marriage of true minds...'. PMID- 11767873 TI - Acquired haemophilia in South Australia: a case series. AB - Of eight cases of acquired haemophilia presenting over an 8-year period, six received immunosuppressive treatment, five with cyclophosphamide, vincristine and prednisolone (CVP). Five patients (four on immunosuppressive treatment) entered remission, two patients died and one was lost to follow up. Initially, the remissions were only partial. The median duration until partial remission was 10 weeks (range 1-55 weeks) and until complete remission was 35 weeks (range 2-59 weeks). Partial remission may proceed to complete remission without further chemotherapy. PMID- 11767874 TI - Behcet's disease with cerebral vasculitis. PMID- 11767875 TI - Spinal meningeal melanocytoma with hydrocephalus and intracranial superficial siderosis. PMID- 11767876 TI - Case of amoebic liver abscess: prolonged latency or acquired in Australia? PMID- 11767877 TI - Hepatic fremitus: 'Monash sign'. PMID- 11767878 TI - Case of Alstrom syndrome with late presentation dilated cardiomyopathy. PMID- 11767879 TI - Management of venous thrombosis in hospital or at home: comparing length of stay. PMID- 11767880 TI - A puzzling editorial decision. PMID- 11767881 TI - Special issue dedicated to Professor Dr. Fritz Hartmann Frimmel on the occasion of his 60th birthday. PMID- 11767882 TI - Monoclonal antibody to polycyclic aromatic hydrocarbons based on a new benzo[a]pyrene immunogen. AB - Benzo[a]pyrenebutyric acid (B[a]PBA) has been synthesized and covalently coupled to bovine serum albumin to generate monoclonal antibodies (Mab). A competitive indirect enzyme-linked immunosorbent assay (ELISA) for polycyclic aromatic hydrocarbons (PAH) has been developed with Mab B[a]P-13. It was shown by testing with 21 parent PAH and 10 compounds carrying methyl, hydroxy, or butyric acid functions that the antibody had broad specificity. Highest affinity was found for four- to six-ring PAH. Different organic co-solvents were tested. No loss in sensitivity, compared with controls in PBS, were found with methanol, dimethyl sulfoxide, and glycerol at final concentrations of 5 to 10%. Further, an observation was made that a modification (fine-tuning) of the affinity and specificity of the antibodies was possible by changing the type of the added organic co-solvent. The high susceptibility of the ELISA with regard to inorganic ions might be an indication of a more hydrophilic binding pocket e.g. involving a pi-cation interaction. Investigation of the effect of pH revealed that for pH between 6 to 9 there was no noticeable impairment. With an LOD as low as 30 pg per well for B[a]P the sensitivity of the ELISA is sufficient for analyses of solvent extracts of many environmental samples. As an example, the determination of a PAH sum parameter, given as B[a]P-equivalents, in crude aerosol extracts by both ELISA and HPLC revealed good correlation (r2=0.717) but approximately five fold overestimation by the immunochemical method, obviously as a result of cross reacting analytes. PMID- 11767883 TI - HG/LT-GC/ICP-MS coupling for identification of metal(loid) species in human urine after fish consumption. AB - Human urine samples after fish consumption have been investigated by low temperature gas chromatography with inductively coupled plasma mass spectrometric detection after sample derivatization by hydride generation (HG/LT-GC/ICP-MS). This analytical technique enabled the identification of organometal(loid) compounds in human urine; species of the six elements germanium, arsenic, selenium, tin, antimony, and mercury were determined. Three different organic selenium species, two germanium species, seven arsenic species, four tin species, five antimony species, and one species of mercury were found; 18 of the 22 species detected could be identified. The relative detection limits ranged between 2 and 12 pg x L(-1) (x=element). These organometal(loid) compounds probably build up in the human body under the influence of micro-organisms, in the presence of hydrogen sulfide and methane, in the human intestine. PMID- 11767884 TI - Determination of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H) furanone (MX) and its analogues by GC-ITD-MS-MS. AB - A new analytical method has been developed for the determination of chlorinated and brominated hydroxyfuranones. The method is based on separation by GC and selective determination of the compounds by use of an ion-trap mass detector. MS MS fragmentation in an ion-trap detector can be regarded as an alternative to high-resolution mass spectrometry. Unique precursor ions were selected from the EI mass spectra and product-ion patterns were studied for a variety of collision energies. From these data, abundant mass transitions were selected for quantification and confirmation of compound identity. The method was applied to a spiked sample of chlorine-disinfected drinking water and it was found that the GC MS-MS procedure is at least as sensitive and selective as previously published methods. PMID- 11767885 TI - Halogenated methyl-phenyl ethers (anisoles) in the environment: determination of vapor pressures, aqueous solubilities, Henry's law constants, and gas/water- (Kgw), n-octanol/water- (Kow) and gas/n-octanol (Kgo) partition coefficients. AB - Halogenated methyl-phenyl ethers (methoxybenzenes, anisoles) are ubiquitous organics in the environment although they are not produced in industrial quantities. Modelling the fate of organic pollutants such as halogenated anisoles requires a knowledge of the fundamental physico-chemical properties of these compounds. The isomer-specific separation and detection of 60 of the 134 possible congeners allowing an environmental fingerprinting are reported in this study. The vapor pressure p0(L) of more than 60 and further physico-chemical properties of 26 available congeners are given. Vapor pressures p0(L), water solubilities S(L)W, and n-octanol/water partition coefficients Kow were determined by capillary HR-GC (High Resolution Gas Chromatography) on a non-polar phase and by RP-HPLC (Reversed Phase High Performance Liquid Chromatography) on a C18 phase with chlorobenzenes as reference standards. From these experimental data the Henry's law constants H, and the gas/water Kgw and gas/n-octanol Kgo partition coefficients were calculated. We found that vapor pressures, water solubilities, and n-octanol/water partition coefficients of the halogenated anisoles are close to those of the chlorobenzenes. A similar environmental fate of both groups can, therefore, be predicted. PMID- 11767886 TI - Determination of aromatic amines in surface waters and comparison of their behavior in HPLC and on sediment columns. AB - An analytical method based on solid-phase extraction (SPE) with a polymeric material, HPLC separation on a modified C18 material, and diode-array detection is presented for the determination of aromatic amines in the ng L(-1) concentration range. These potentially toxic compounds in polluted water samples can be sampled by using SPE with an amino phase to clean the eluate. Column experiments were performed to characterize the transport behavior of aromatic amines in an aquifer sediment. For nineteen aromatic amines, linear correlations were found between the adsorption coefficient, Kd, estimated from column experiments, and capacity factors, k', measured by isocratic reversed-phase HPLC (RPHPLC). PMID- 11767887 TI - Development of an element-selective monitoring system for adsorbable organic halogens (AOX) with plasma emission spectrometric detection for quasi-continuous waste-water analysis. AB - An automated quasi-continuously-operating monitor has been developed for element selective analysis of adsorbable organic halogens (AOX) in water. After extensive optimization the automatic method was applied to the analysis of standard solutions and real waste water samples to prove its analytical applicability. The new instrument is based on the element-selective analysis of halogens by means of a spectroscopic detection system consisting of a microwave-induced helium plasma excitation source (TM010-type; developed in this laboratory) and the plasma emission detector (PED) which operates with oscillating narrow-band interference filters. After enriching the organic components on activated charcoal and pyrolysis in an oxygen stream at 950 degrees C, in accordance with DIN/EN 38409,H14/1485, interfering CO2 and H2O gas generated during combustion is removed from the analytes in the so-called ELSA-system (element-selective AOX analyzer). For focused injection into the plasma excitation source the analytes (hydrogen halides) are trapped in a deactivated fused silica capillary at -180 degrees C; this is followed by identification and quantification on the basis of element-specific emission of radiation in the VIS and NIR-region (chlorine 837.6 nm, fluorine 685.6 nm). Bromine and iodine could not be detected with satisfactory inter-element selectivity, because of spectral interferences caused by matrix elements, and so results from the respective single-element investigations for determination of AOBr and AOI are not presented. The procedure has been validated and the analytical performance has been examined by calibration with p-chlorophenol and p-fluorophenol. The limit of detection was 1.1 microg (absolute) for chlorine and 6.6 microg (absolute) for fluorine. PMID- 11767888 TI - An N,N'-dialkyl-4,4'-bipyridinium-modified titanium-dioxide photocatalyst for water remediation--observation and application of supramolecular effects in photocatalytic degradation of pi-donor organic compounds. AB - The photocatalytic activity of TiO2 (Degussa P-25) modified with a 4,4' bipyridinium monolayer (V2+-TiO2) has been compared with that of conventional TiO2-P-25 by investigating the efficiency of degradation of a series of four organic model compounds with increasing pi-donor capacity (2,4-xylidine, 2,4 dimethylphenol, hydroquinone, and dimethylhydroquinone). As far as the mechanism of the first oxidation reaction is concerned, evidence for the formation of supramolecular donor-acceptor complexes with the bipyridinium units at the semiconductor surface was obtained by comparison of the Langmuir-adsorption characteristics and the efficiencies of photodegradation of the different substrates. Furthermore, the main intermediates of the photocatalytic degradation of 2,4-xylidine were identified, and the presence of 2,4-dimethylphenol indicates that the main pathway of substrate oxidation proceeds via electron transfer from the adsorbed organic substrate to the "holes" within the valence band of the photoexcited semiconductors V2+-TiO2 and TiO2. The efficiencies of photocatalytic degradation by both V2+-TiO2 and TiO2 were limited by the trapping efficiency of the conduction band electrons by molecular oxygen. PMID- 11767889 TI - New application of a traditional analytical method--arsenic removal from water works sludge during iron(III) chloride coagulant production. AB - The Marsh Test, the original means of determination of arsenic by hydride generation, has been modified to remove arsenic from water works sludge, with iron used instead of zinc as the main agent. Water works sludge (main compound iron(III) oxyhydrate) generated during groundwater treatment can be enriched in arsenic up to several gkg(-1). Acidic dissolution of this sludge to produce FeCl3 coagulant liberates the arsenic. Addition of elemental iron reduces this dissolved As(V) mainly to dispersed elemental As(0) particles, which can be removed by filtration. If the reaction temperature is kept below 50 degrees C, more than 99% of the arsenic can be removed from the coagulant solution and less than 10% will escape as gaseous arsine (AsH3). Severe foaming and silicic acid gel formation occurs during the acidic dissolution, however. For technical and economic reasons the use of the water works sludge for FeCl3 coagulant production is not competitive when compared with other recycling methods. PMID- 11767890 TI - Standardized particle size for monitoring, inventory, and assessment of metals and other trace elements in sediments: <20 microm or <2 microm? AB - Despite the manifold factors that determine the composition of a river sediment (e.g., geology, soil type, rural or highly industrialized and densely populated, as well as forested areas, concentration of carbonates and organic matter), the linear regressions between the 9 metals determined in the fractions <2 microm and <20 microm have high coefficients (R2 after Pearson) for Cr and Cu (both 0.94), followed by Pb (0.90), Cd (0.82), Zn (0.81), Ni (0.76), and Mn (0.72). Low and very low coefficients are found for Hg (0.51) and Fe (0.22). In addition, the histograms of the metal ratios <2 microm:<20 microm (i.e. the slope of a linear regression) show that--with the exception of Cd (1.47)--all median ratios of the other metals fall within a narrow range (1.24-1.35). Both "fine" (<2 microm and <20 microm) fractions are able to fulfil the requirements for monitoring, inventory, and assessment of metals in sediments. Preference should be given to the rapid, simple, and economic <20 microm separation by sieving; this fraction corresponds fairly closely to the former suspended load of a riverine transport. PMID- 11767891 TI - Inert sampling and sample preparation--the influence of oxygen on heavy metal mobility in river sediments. AB - Two approaches have been used to investigate changes in the nature of metal binding in river sediments caused by atmospheric oxygen. Firstly, non-inert and inert sample preparation were applied, in combination with sequential extraction, to determine for which metals inert sample preparation is necessary for correct determination of metal mobility under environmental conditions. Secondly, the metal contents of sediments sampled before and after a river weir were fractionated by sequential extraction to study the effect of the oxygen impact at the weir on heavy metal mobility in the sediments. Different grain-size fractions from one sample were also extracted, to enable selection of the upper grain-size limit most suitable for answering this analytical question. The results showed the need for the inert sample preparation technique for Cd, Zn, Pb, Mn, and Fe, but not for Co, Ni, Cu, and Cr. No significant change of heavy metal mobility at the weir could be proved, although the mobilization behavior of some elements was different. The optimum upper grain-size limit was 63 microm. PMID- 11767892 TI - Impact of natural nanophases on heavy-metal retention in zeolite-supported reactive filtration facilities for urban run-off treatment. AB - The retention of lead in zeolite-supported sand-filter columns has been tested with focus on the effect of potentially mobile natural nanophases (natural colloids, humic substances). It could be shown that interaction of lead with natural nanophases enhanced the mobility of the contaminant. In the presence of iron oxide particles (goethite) a normal breakthrough of lead was observed. Humic substance can act as a carrier for lead itself and can enhance the mobility of lead bound to inorganic nanophases, because of the increased mobility of the nanophases in the presence of humic substances. PMID- 11767893 TI - On-site characterization of humic-rich hydrocolloids and their metal loading by means of mobile size-fractionation and exchange techniques. AB - Humic-rich hydrocolloids and their metal loading in selected German bog-waters have been characterized by a novel on-site approach. By use of an on-line multistage ultrafiltration (MST-UF) unit equipped with conventional polyethersulfone (PES)-based flat membranes (nominal cut-off 0.45, 0.22, and 0.1 microm, or 100, 50, 10, 5, 3 kDa) the hydrocolloids could be fractionated on-site in both sub-particulate and macromolecular size ranges. Characterization (dissolved organic carbon (DOC), metals) of the colloid fractions obtained this way was performed off-site by use of conventional instrumental methods (carbon analyzer, AAS, ICP-OES, and TXRF (total reflection X-ray fluorescence)). Major DOC fractions of the hydrocolloids studied were found to be in the size range <5 kDa. The assessed metals (Al, Cu, Fe, Mn, Pb, and Zn) were, however, predominantly enriched in the macromolecular and sub-particulate range, depending on the metal and the sample, respectively. In addition, metal species bound to these hydrocolloids were kinetically characterized on-site by use of competitive ligand (EDTA (ethylenediaminetetraacetate)) and metal (Cu(II)) exchange; the EDTA complexes formed and the metal ions exchanged were separated by means of a small time-controlled tangential-flow UF unit (cut-off 1 kDa). Bound metal fractions, in particular Al and Fe, reacted only slowly (500 to 1000 min) with EDTA; the conditional availability was 60-99%, depending on the hydrocolloid. In contrast, the Cu(II) exchange of colloid-bound metal species approached equilibrium within 5-10 min, with characteristic exchange constants, Kex, of the order of 0.01 to 90 for the metals (Fe or = 6 times during the baseline phase, females were significantly more likely to respond to treatment (> or = 50% reduction in marking frequency) than were males. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that male cats and cats from multicat households are more likely to exhibit urine marking behavior than females and cats from single-cat households. Results also suggest that attention to environmental and litter box hygiene can reduce marking frequency in cats, regardless of sex or household status of the cats, and may come close to resolving the marking problem in some cats. PMID- 11767920 TI - Capnographic monitoring of anesthetized African grey parrots receiving intermittent positive pressure ventilation. AB - OBJECTIVE: To determine whether end-tidal partial pressure of carbon dioxide (PETCO2) correlated with PaCO2 in isoflurane-anesthetized African grey parrots receiving intermittent positive pressure ventilation (IPPV). DESIGN: Prospective study. ANIMALS: 14 healthy mature African grey parrots (Psittacus erithacus timnus). PROCEDURE: Each bird was anesthetized via mask with isoflurane, intubated, and connected to a pressure-limited intermittent-flow ventilator. Respiratory rate was altered while holding peak inspiratory pressure constant (5 cm H2O) to achieve a PETCO2 in 1 of 3 ranges: < 30 mm Hg, 30 to 40 mm Hg, and > 40 mm Hg. Blood was collected from the superficial ulnar artery of each bird at least once during each of the 3 ranges. Arterial blood samples were collected for blood gas analysis while PETCO2 was recorded simultaneously. RESULTS: A strong correlation between PETCO2 and PaCO2 was detected over a wide range of partial pressures, although PETCO2 consistently overestimated PaCO2 by approximately 5 mm Hg. End-tidal partial pressure of CO2 and PaCO2 also correlated well with arterial blood pH, and the acute response of the bicarbonate buffer system to changes in ventilation was similar to that of mammals. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that PETCO2 reliably estimates PaCO2 in isoflurane anesthetized African grey parrots receiving IPPV and suggest that IPPV combined with capnography is a viable option for anesthetic maintenance in avian anesthesia. PMID- 11767921 TI - Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German Shepherd Dogs, Golden Retrievers, Labrador Retrievers, and Rottweilers. AB - OBJECTIVE: To determine whether age, breed, sex, weight, or distraction index (DI) was associated with the risk that dogs of 4 common breeds (German Shepherd Dog, Golden Retriever, Labrador Retriever, Rottweiler) would have radiographic evidence of degenerative joint disease (DJD) associated with hip dysplasia. DESIGN: Cross-sectional prevalence study. ANIMALS: 15,742 dogs. PROCEDURE: Hips of dogs were evaluated radiographically by use of the ventrodorsal hip-extended view, the compression v ew, and the distraction view. The ventrodorsal hip extended view was examined to determine whether dogs had DJD. For each breed, a multiple logistic regression model incorporating age, sex, weight, and DI was created. For each breed, disease-susceptibility curves were produced, using all dogs, regardless of age, and dogs grouped on the basis of age. RESULTS: Weight and DI were significant risk factors for DJD in all breeds. For German Shepherd Dogs, the risk of having DJD was 4.95 times the risk for dogs of the other 3 breeds combined. In all breeds, the probability of having DJD increased with age. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the probability of having hip DJD increased with hip joint laxity as measured by use of DI. This association was breed-specific, indicating that breed-specific information on disease susceptibility should be incorporated when making breeding decisions and when deciding on possible surgical treatment of hip dysplasia. PMID- 11767922 TI - Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs. AB - An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs. PMID- 11767923 TI - Omentalization of cystic sublumbar lymph node metastases for long-term palliation of tenesmus and dysuria in a dog with anal sac adenocarcinoma. AB - A 13-year-old castrated male Bassett Hound was examined because of a 2-week history of severe constipation and tenesmus. Radiography revealed a large cystic mass in the caudal portion of the abdomen that was compressing the urethra and obstructing the pelvic canal. A small perianal mass was also noticed in the region of the left anal sac. Exploratory surgery was performed, but the mass was deemed unresectable. Instead, the mass was incised, drained, and omentalized in an attempt to establish continuous drainage after surgery. Cytologic evaluation of the perianal mass was consistent with a diagnosis of anal sac adenocarcinoma. Histologic evaluation of the abdominal mass revealed it was a lymph node effaced by adenocarcinoma. Despite the poor prognosis for anal sac adenocarcinoma with metastatic spread to the sublumbar lymph nodes, tenesmus and dysuria in this dog remained palliated until the dog's death 18 months after surgery. Omentalization was successful in providing a continuous method of fluid drainage for this cystopapillary abdominal tumor. PMID- 11767924 TI - Secondary hypoparathyroidism attributed to hypomagnesemia in a dog with protein losing enteropathy. AB - Severe hypomagnesemia (0.8 mg/dl; reference range, 1.6 to 2.3 mg/dl), hypocalcemia, and protein-losing enteropathy were identified in a 5-year-old castrated male 3-kg (6.6 lb) Shih Tzu examined because of anorexia, lethargy, paresis, and abdominal distention. Histologic examination of intestinal biopsy specimens revealed lymphangiectasia and lymphocytic, plasmacytic, neutrophilic infiltrates. Initial treatment included administration of magnesium (0.80 mEq/kg [0.36 mEq/lb]) of body weight in a balanced electrolyte solution. This treatment resulted in normalization of the serum magnesium concentration (1.7 mg/dl); resolution of the lethargy, paresis, and tachycardia; and an increase in the serum parathyroid hormone and ionized calcium concentrations. Findings were consistent with secondary hypoparathyroidism attributable to hypomagnesemia. Magnesium concentration should be monitored in all dogs with gastrointestinal tract disease, especially those with protein-losing enteropathy, anorexia, and weakness. PMID- 11767925 TI - Treatment of a granuloma caused by Halicephalobus gingivalis in a horse. AB - A 12-year-old Arabian gelding with a granuloma caused by the nematode Halicephalobus gingivalis caudal and dorsal to the left orbit was examined. There was no evidence of dissemination of the nematode to the kidneys or the CNS, and the horse was treated with ivermectin (1.2 mg/kg [0.55 mg/lb] of body weight, p.o., every 2 weeks for 3 treatments). The granuloma was surgically debulked 2 days after the first dose of ivermectin. The granuloma resolved with no evidence of nematode infection after 18 months. Halicephalobus gingivalis is a ubiquitous saprophytic nematode that has been reported to infect humans and horses. The nematode may form granulomas in the integument or may disseminate to various organs with a tropism for the CNS and kidneys. Once clinical signs of CNS involvement develop, the disease is rapidly fatal. PMID- 11767926 TI - Health and performance of young dairy calves vaccinated with a modified-live Mannheimia haemolytica and Pasteurella multocida vaccine. AB - OBJECTIVE: To evaluate the health and performance of young dairy calves vaccinated with a commercial Mannheimia haemolytica and Pasteurella multocida vaccine. DESIGN: Randomized clinical trial. ANIMALS: 358 Holstein dairy calves between 14 and 20 days of age on 8 farms. PROCEDURE: Calves were randomly assigned to a control or vaccinated group. The vaccine used was a commercial modified-live M. haemolytica and P. multocida vaccine that was administered on days 0 and 14. Calf weight was measured on day 0 and monthly for 3 months. Farmers were asked to record any treatment given to the calves and the reason for treatment during the 4 months of the study. Blood was collected from all calves on days 0 and 28, and titers of antibodies to M. haemolytica were determined by means of direct bacterial agglutination. RESULTS: Mean daily gain was not significantly different between vaccinated and control calves. Vaccinated calves had a significantly greater increase in antibody titers (5.3-fold increase), compared with control calves (3.6-fold increase). There was no significant difference between vaccinated and control calves for any of the treatment outcomes (number and duration of treatments and age at first and last treatments). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the M. haemolytica and P. multocida vaccine, given twice 2 weeks apart, was effective in increasing titers of antibodies against M. haemolytica in young dairy calves but did not improve calf performance or health. PMID- 11767927 TI - The origin of a nicotine detection method. PMID- 11767928 TI - Replotting data for chronic beryllium disease. PMID- 11767929 TI - Interchangeability of gas detection tubes and hand pumps. PMID- 11767930 TI - An evaluation of industrial ventilation troubleshooting methods in experimental systems. AB - This study determined the efficacy of specific methods of identifying and locating obstructions and alterations to industrial exhaust ventilation systems under challenging conditions when measurement errors were minimized. Two traditional screening methods were evaluated: (1) two variations of the hood static pressure method and (2) a severely modified version of the "Check-out" method. Three proposed pressure ratio methods also were evaluated and compared with the traditional methods. Two full-sized experimental ventilation systems in two ventilation laboratories were tested. One system had five branch ducts, the other had eight, with branch duct diameters ranging from 4 to 7 inches. To create challenge, each system received multiple alterations and, in some cases, the airflow level was changed throughout the system. For each round of measurements (1) different combinations of alterations were made to some ducts; (2) on a given system, relevant pressures and flows were determined for each duct using calibrated pressure sensors and standard pitot tubes held in a traversing device; and (3) the numbers of true and false positives and negatives for each screening method were computed for a broad range of threshold values. Sensitivities were plotted against the false positive rates for all thresholds for each method. The area (AROC) under the resulting "receiver operating characteristic curves" was computed for each method. Variability was simulated using bootstrap methods to determine significance of differences. In addition, the thresholds that would achieve 10 and 20% false positive rates were determined for each method and the accompanying sensitivities compared. The pressure ratio methods detected nearly all nontrivial obstructions with nearly zero false positives (AROC=1). The direct pressure comparison methods showed substantially inferior performance for the substantial challenges presented in these tests. The latter may be useful under less challenging conditions but were of dubious utility in locating obstructions under the ranges of conditions tested. PMID- 11767931 TI - The use of reverse diffusion to validate the performance of diffusive samplers. AB - A number of different protocols have been put forth for measuring reverse diffusion from diffusive samplers. The basic concept is that reverse diffusion tests, depending as they do on basic laws of mass transfer, are not independent of one another, but may give general information about the limits to the possible change that can occur if the conditions to measure reverse diffusion are changed. Laboratory measurements of the reverse diffusion of vinyl chloride, using 3M and SKC diffusive samplers, following both the National Institute for Occupational Safety and Health (NIOSH) and the European Union test protocols, support the mathematical analysis developed in this article. An important conclusion is that if in following the NIOSH protocol a diffusive sampler loses 10% of its analyte over a period of 4 hours, then the maximum loss expected from a sampler allowed to back-diffuse for 8 hours is 19%. PMID- 11767932 TI - Telephone communications with several commercial respirators. AB - Previous work showed that telephone communications while wearing military respirators degraded both word comprehension and recognition speed. In addition, electronic amplification of the speech diaphragm signal had shown no advantage to the extra hardware. This experiment was performed to test effects of different configurations of commercially available respirators on telephone communications accuracy and speed. Twelve pairs of subjects were separated into different rooms and communicated by telephone. Modified rhyme-test words were presented by computer to the speaker, who transmitted the word by telephone to the listener. During the first replication, subjects were given no instruction about telephone communications procedure. During the second replication subjects followed a communications protocol that instructed them when to move the telephone handset from their ears to their mouths. Results showed that the protocol uniformly improved communications accuracy without incurring any extra time penalty. Word comprehension was still twice as fast without a respirator as with a respirator. Accuracy with the protocol nearly equaled the no respirator control value for most respirators tested. PMID- 11767933 TI - Successful reduction of morticians' exposure to formaldehyde during embalming procedures. AB - A case study of the effectiveness of upgraded ventilation engineering controls in a military mortuary facility was performed. Worst-case mortician formaldehyde exposures generated during the use of highly concentrated embalming fluid (required to meet a 2-week preservation standard for overseas case processing and return of the deceased to the continental United States) were documented. A detailed exposure evaluation via consecutive short-term exposure limit (STEL) samples facilitated characterization of the hazard potential for each distinct phase of the embalming process. After baseline screening with 3M passive formaldehyde dosimeters, a total of 145 personal and area STEL sorbent tube samples were collected during six embalming cases between 1994 and 1998. Prior to the installation of local exhaust ventilation controls, personal time-weighted average (TWA) exposure values during embalming activities were 3.19-7.69 ppm for a mean of 4.80 ppm (calculated 8-hour TWA exposures for mortician workshifts were 1.32-2.86 ppm, mean 1.93 ppm). Initial STEL exposures ranged from a low of 0.14 during preembalming body preparation to 20.89 ppm during aspiration of arterial fluids (mean = 4.16 ppm). Embalming room general area samples revealed a mean concentration of 0.76 ppm. With ventilation upgrades installed in 1997, calculated personal 8-hour TWA exposure values during embalming procedures were reduced. STEL exposures decreased to between 0.11 to 3.44 ppm (mean of 0.55 ppm); embalming room general area sample concentrations decreased to a mean of 0.089 ppm. Because occasional 15-min peak exposures continued to exceed the 2.0 ppm Occupational Safety and Health Administration STEL during tasks involving large volumes of embalming fluid or direct contact with paraformaldehyde preservative powders, general room ventilation was further upgraded to 25 room air changes per hour. PMID- 11767934 TI - Approaches and considerations for setting occupational exposure limits for sensory irritants: report of recent symposia. AB - Over the past 50 years significant strides have been made in reducing occupational exposure to airborne chemicals. To a large extent, the impetus behind the reductions has been the identification of presumably safe levels of exposure, or occupational exposure limits (OELs). Most of the reduction in exposure has been to chemicals such as hepatotoxins, neurotoxins, nephrotoxins, and carcinogens that cause frank toxic effects. Recently, however, a number of industrial hygiene and occupational medicine initiatives have sought to identify acceptable levels of exposure to sensory irritants and reduce exposure to this class of chemicals. This article presents an overview of the field with emphasis on the work presented at two symposia sponsored by the Chemical Manufacturers Association: "How Do We Set an Occupational Exposure Limit (OEL) for Irritation?" (1998) at the American Industrial Hygiene Conference and Exposition and "Respiratory Tract Irritation and Olfaction Conference" (1997). The two symposia reviewed clinical and experimental methods used to assess odor and sensory irritation, to increase understanding of the research needed to establish OELs for sensory irritants, and to discuss how to use this information to identify appropriate values. The symposia illustrated that research in this area is evolving quickly and that there is already sufficient understanding to permit scientists to identify chemicals likely to be sensory irritants. Further, there appears to be an ample number of research methods for identification of airborne concentrations that should protect most workers. This article summarizes some of the key points raised at these symposia and suggests areas deserving of future study. PMID- 11767936 TI - The assessment of irritation using clinical methods and questionnaires. AB - Sensory irritant responses to chemical exposures are measured by a variety of methods; however, studies can be influenced from biases associated with study design and subject responses. This article reviews the different methods used to quantitate irritation. These methods primarily focus on eye and nasal mucosal irritation. Although methods to evaluate mouth, throat mucosal, and dermal irritation are also relevant, they are seldom used in actual practice. Measurements for eye irritation include tear film stability, epithelial damage, foam formation, blinking frequency, tear flow, inflammation, and hyperemia. Methods for detecting nasal mucosa irritation include measuring swelling of the nasal mucosa, peak airflows through the nose, acoustic rhinometry, and rhinostereometry, which measures thickness of the anterior nasal turbinate. Questionnaires are useful for defining a set of symptoms in an attempt to characterize dose-response relationships from controlled exposure studies or field studies, to compare rates of events in field studies, or to screen for disease. However, it is important to consider carefully the study design, goal of utilization, and constraints surrounding their application. Whichever method is used in medical surveillance or to evaluate effectiveness of industrial hygiene or engineering controls in preventing irritation effects from chemical exposure, the sensitivity, specificity, and predictive value of the irritation measurements are important factors in interpreting the results. This article reviews these various issues and offers some advice. PMID- 11767935 TI - Psychophysical methods in the study of olfaction and respiratory tract irritation. AB - This article describes the fundamentals of olfaction and irritation perception and the dominant psychophysical methods for the assessment of olfaction and respiratory tract irritation. It also discusses factors that determine the olfactory and irritant response (ranging from the physicochemical properties of the stimulus to the physiological and cognitive characteristics of the individual). Because the vast majority of volatile chemicals stimulate the olfactory system at concentrations well below that at which they will elicit trigeminal activation, the evaluation of irritation from volatiles is often confounded by the perception of odor. Several methods have been used for studying the perception of irritation, without the influence of olfaction. The perception and reports of acute adverse effects of odor, annoyance, and irritation from volatile chemicals have multiple determinants. Understanding the perceptual impact of chemicals under environmentally realistic conditions requires attending to both the sensory and the psychological impact of those exposures. The review, which is largely based on presentations given by Dr. Richard Doty and Dr. William Cain, concludes by discussing the importance of the psychophysical approach, which considers physiochemical, subject, experimental, and cognitive/ psychological factors, for research in the chemical senses. PMID- 11767937 TI - Approaches to understanding chemosensory responses: new directions and new caveats. AB - This article describes recent research on sensory irritants that should prove helpful to setting occupational exposure limits (OELs) for this class of chemicals. In addition, background information is provided to assist in recognizing the relevance and importance of this type of work. Research conducted by Dr. Steven Youngentob and others addresses the recovery of olfactory function following exposure to high concentrations of sensory irritants. Their research has combined several different experimental methods to gain insight on how olfactory receptor neurons (ORNs) are replaced. Other important work relevant to setting OELs has been conducted by Professor Gerd Kobal, who has relied on human brain imaging during chemosensory stimulation. Commentary on these two approaches is followed by suggestions on how to address the relative lack of detailed normative information on human responses to odors and irritants. PMID- 11767938 TI - Evaluating the human response to sensory irritation: implications for setting occupational exposure limits. AB - Although animal models of sensory irritation have led to the development of useful assays for evaluating the potency of chemical irritants, the importance of conducting human exposure studies to model and understand the human response to sensory irritants cannot be minimized. In recent years a series of tests have been developed for humans that can be safely conducted and that can provide excellent data on which to base occupational exposure limits. This article delineates the major issues involved in the evaluations of sensory irritation in humans. Among these issues are the differences between odor and irritation, irritation and slight toxicity, adaptation and habituation, as well as personal expectation about discomfort and the reported irritation. The article also describes psychophysiological and electrophysiological methods for assessing sensory irritation. Some of the possible confounders that can influence the results of human tests involving sensory irritants are addressed. PMID- 11767939 TI - Setting occupational exposure limits for sensory irritants: the approach in the European Union. AB - Beginning in 1990, the European Commission initiated a program to establish European Union (EU)-wide occupational exposure limits (OELs). As in the United States and other countries, a panel of experts known as the Scientific Committee on Occupational Exposure Limits (SCOEL) was identified and brought together to identify the proper values. This article describes the approach used by SCOEL to identify appropriate values for sensory irritants. The EU panel believes that irritant effects in the eyes and respiratory tract can produce symptoms that range from trivial to serious, and that responses to irritants may be viewed as belonging to a continuum. One of the interesting differences between the approach used by the ACGIH TLV committee and the SCOEL is the use of five grades of irritation to evaluate this class of chemicals. For purposes of setting an OEL, the SCOEL makes no distinction between irritation or nuisance and related somatic effects such as headache. How the committee established an OEL for ethyl acetate is offered as an illustrative example. PMID- 11767940 TI - Approach to setting occupational exposure limits for sensory irritants in The Netherlands. AB - This article describes how scientists in the Netherlands set occupational exposure limits (OELs) for sensory irritants. When they tackle this issue, a number of key questions need to be answered. For example, did the studies indeed measure sensory irritation and not cytotoxicity? When the irritant is an odorant, can interference of olfactory stimulation be excluded? In the case of subjective measurements, can psychological irritation be excluded? When adaptation is an issue, did the studies indeed measure adaptation and not habituation? When OELs are established in the Netherlands, each of these issues is carefully addressed before a value is suggested. When setting an OEL in the Netherlands, human data carry more weight than animal data of comparable quality. As in the United States, documentation for the recommended OEL is written and a discussion of all available relevant and reliable data culminating in the selection of the key study for deriving the health-based recommended occupational exposure limit is provided. Special effort is dedicated to reconciling differences between the animal and human data. If the toxicological database is considered to be inadequate, the committee acknowledges this limitation and will not recommend a limit value due to insufficient data. PMID- 11767941 TI - PAT Program Report: background and current status. PMID- 11767942 TI - An overview of endosymbiotic models for the origins of eukaryotes, their ATP producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. AB - The evolutionary processes underlying the differentness of prokaryotic and eukaryotic cells and the origin of the latter's organelles are still poorly understood. For about 100 years, the principle of endosymbiosis has figured into thoughts as to how these processes might have occurred. A number of models that have been discussed in the literature and that are designed to explain this difference are summarized. The evolutionary histories of the enzymes of anaerobic energy metabolism (oxygen-independent ATP synthesis) in the three basic types of heterotrophic eukaryotes those that lack organelles of ATP synthesis, those that possess mitochondria and those that possess hydrogenosomes--play an important role in this issue. Traditional endosymbiotic models generally do not address the origin of the heterotrophic lifestyle and anaerobic energy metabolism in eukaryotes. Rather they take it as a given, a direct inheritance from the host that acquired mitochondria. Traditional models are contrasted to an alternative endosymbiotic model (the hydrogen hypothesis), which addresses the origin of heterotrophy and the origin of compartmentalized energy metabolism in eukaryotes. PMID- 11767943 TI - A microsomal ecdysone-binding cytochrome P450 from the insect Locusta migratoria purified by sequential use of type-II and type-I ligands. AB - A dual-affinity method was established to purify, for the first time, a microsomal ecdysone-binding cytochrome P450 protein from locust Malpighian tubules. This method involved, after prepurification on omega-octylamino-agarose and hydroxylapatite, binding of cytochrome P450 to an immobilized triazole-based general P450 inhibitor (type-II ligand) followed by elution with the substrate ecdysone (type-I ligand) of the bound cytochrome. The isolated material showed a typical cytochrome P450 spectrum, a specific heme content of 13 nmol/mg protein, and a prominent protein of about 60 kDa on SDS-PAGE. Based on a tryptic undecapeptide sequence the isolated protein may be identical to CYP6H1, a putative ecdysone 20-monooxygenase recently cloned from the same tissue. Ecdysone 20-monooxygenase activity could be partially reconstituted from microsomal detergent extracts, when supplemented with purified bovine cytochrome P450 reductase and detergent-extracted microsomes; reconstitution was not successful with any chromatographic fraction, however. Therefore, purification of the locust cytochrome P450 was monitored by ecdysone-induced type-I difference spectra, whenever applicable, in addition to carbon monoxide spectra. Affinity columns with matrix-bound diethylstilbestrol and testosterone 3-thiosemicarbazone, but not with the 17beta-hemisuccinate, yielded elution profiles with ecdysone that were comparable to those of the triazole matrix. The concept of dual-affinity chromatography described here may be generally applicable to the isolation of cytochromes P450. PMID- 11767944 TI - The large cytoplasmic loop of the glucose transporter GLUT1 is an essential structural element for function. AB - Alanine scanning mutagenesis and the introduction of deletions and insertions were used to address the role of the large cytoplasmic loop in 2-deoxy-D-glucose (2-DOG) uptake by GLUT1 expressed in Xenopus oocytes. Alanine scanning mutagenesis of 29 amino acid residues that are identical or homologous in GLUT1 to GLUT4 demonstrated that the transport activities of only a few variants were affected. Progressive truncation of the loop by six deletions leaving intact 59 (delta236-241), 49 (delta231-246), 39 (delta226-251), 28 (delta221-257), 18 (delta216-262), or 10 (delta213-267) amino acid residues resulted in a progressive decrease in 2-DOG uptake. Compared with wild-type GLUT1 the uptake rates varied between 33% for the delta236-241 mutant and 4% for the delta213-267 mutant. Insertional mutagenesis using hexaalanine or hexaglycine to fill in the deletion 236D-241L restored 2-DOG uptake to 73% of wild-type GLUT1 in the case of hexaalanine, whereas hexaglycine insertion was without effect. Confocal laser microscopy demonstrated that a deletion of six amino acid residues did not influence the expression level in the plasma membrane (delta236-241 mutant), whereas the plasma membrane fluorescence of the delta213-267 mutant was comparable with that of water-injected Xenopus oocytes. Computer-aided secondary structure prediction of the loop suggested that it consists of a long alpha-helix bundle interrupted or kinked by the highly conserved glycine-233. PMID- 11767945 TI - Visual representation by atomic force microscopy (AFM) of tomato spotted wilt virus ribonucleoproteins. AB - Atomic force microscopy (AFM) allows the observation of biological material without fixation procedures. Here we present AFM images of ribonucleoproteins (nucleocapsids) derived from a plant infecting RNA virus (tomato spotted wilt virus, TSWV), which have been recorded in contact mode. The nucleocapsids, prepared from systemically infected leaves of tobacco, were spreaded on a glass surface and dried in air, and appeared as regularly formed rings, resembling the proposed pseudocircular and panhandle structure of encapsidated genomic RNA. Average values between 1300 and 2200 nm of nucleocapsid lengths could be related to dimensions estimated by electron microscopy, thereby validating a filamentous configuration of the TSWV ribonucleoproteins. However, to our knowledge regular, ring-like forms of ribonucleoproteins have not been obtained by electron microscopy, which rather showed an amorphous structure of the virus particles. Hence, the AFM approach provides a starting point for further detailed studies on TSWV ribonucleoprotein complexes. PMID- 11767946 TI - Elimination of hydrocortisone from the medium enables tissue plasminogen activator gene expression by normal and immortalized nonmalignant human epithelial cells. AB - Human cervical epithelial cells transfected and immortalized with human papillomavirus type 16 DNA (HCE16/3) can be, like many other epithelial cells, normally grown in medium supplemented with epidermal growth factor, cholera toxin, hydrocortisone, insulin, transferrin, thyroid hormone and serum. We found that hydrocortisone diminished tissue plasminogen activator (tPA) production to an undetectable level. The removal of hydrocortisone increased urokinase plasminogen activator (uPA) activity within 24-48 h and tPA activity within 48-72 h, and converted the cells to a more elongated and fibroblastic phenotype. Upregulation of uPA mRNA was seen as early as at 3 h and of tPA mRNA within 48-72 h. Higher molecular weight forms (97-110 kDa) of plasminogen activators were seen in zymograms, apparently complexed with PAI-1, starting at 6 h both in the presence and absence of hydrocortisone. Immunoprecipitation with a PAI-1 monoclonal antibody confirmed that both uPA and tPA were complexed. We also studied normal diploid human bronchial epithelial cells (NHBE) and NHBE cells transformed with an adeno-12/SV40 hybrid virus (BEAS-2B). In both types of nonmalignant epithelial cells, the removal of hydrocortisone increased uPA activity. The omission of hydrocortisone increased tPA levels significantly in BEAS-2B cell cultures, and in NHBE cell cultures tPA became detectable at 72 h. No PA complexes were seen in these two cell types. We conclude that normal and immortalized nonmalignant epithelial cells produce tPA, but only if hydrocortisone is omitted in the growth medium. PMID- 11767947 TI - Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis. AB - We report the complete coding sequence and the partial amino acid sequence (determined by chemical sequencing) of Staphylococcus epidermidis extracellular cysteine (Ecp) and serine (Esp) proteases. The first enzyme shows an extended sequence similarity to Staphylococcus aureus cysteine protease (staphopain) and the second one resembles the serine protease produced by that species. The region directly upstream of the sequence coding for the mature protein in both enzymes displays significant homology to the profragments encoded by sspB and sspA, respectively, thus suggesting that the characterised enzymes may also be produced as proproteins. Furthermore, we report some biological properties of the cysteine protease, contributing to a better understanding of its role as a possible virulence factor. The proteolytic activity of this enzyme was rapidly and efficiently inhibited by human alpha-2-macroglobulin; however, human kininogen as well as cystatins (A, C and D) were not inhibitory. Moreover, the protease was capable of inactivating, by limited proteolysis, both alpha-1-antitrypsin and HMW kininogen, but neither alpha-1-antichymotrypsin nor antithrombin III. PMID- 11767948 TI - Splice variants of human cathepsin L mRNA show different expression rates. AB - Human cathepsin L (hCATL) mRNA occurs in vivo in at least three splice variants. They differ in the length of exon 1, which comprises 278 nucleotides (hCATL-A), 188 nucleotides (hCATL-A2) and 132 nucleotides (hCATL-A3), respectively. We describe here the shortest variant for the first time. This form is predominant in all tissues and cells examined so far, including malignant tumors. We studied the expression rate of the three mRNA variants in order to explain why malignant kidney tumors show low cathepsin L activity despite of high mRNA levels. The variant hCATL-A3 showed the highest expression rate in vitro and in vivo. Based on these results, we suggest a cis-acting element on human cathepsin L mRNA which can be bound by a negative trans-acting regulator, thus leading to reduced expression rates. PMID- 11767949 TI - Osmolytes as modulators of conformational changes in serpins. AB - Protein misfolding and aggregation play an integral role in many diseases. The misfolding of the serpin (SERine Proteinase INhibitor) alpha1-antitrypsin results in the accumulation of insoluble polymers within hepatocytes and alpha1 antitrypsin deficiency in plasma, predisposing patients to liver cirrhosis and emphysema. We have examined the effect of three naturally occurring osmolytes, sarcosine, glycine betaine and trimethylamine N-oxide, on conformational changes in alpha1-antitrypsin. All three solutes protected native alpha1-antitrypsin against thermally induced polymerisation and inactivation in a concentration dependent manner. Further spectroscopic analysis showed that sarcosine stabilises the native conformation of alpha1-antitrypsin, thus hindering its conversion to an intermediate state and subsequent polymerisation. On refolding in the presence of sarcosine, alpha1-antitrypsin formed a heterogeneous population, with increasing proportions of molecules adopting an inactive conformation in higher concentrations of the osmolyte. These data show that sarcosine can be used to prevent abnormal structural changes in native alpha1-antitrypsin, but is ineffective in facilitating the correct folding of the protein. The implications of these results in the context of conformational changes and states adopted by alpha1-antitrypsin are discussed. PMID- 11767950 TI - Protective activity of aromatic amines and imines against oxidative nerve cell death. AB - Oxidative stress is a widespread phenomenon in the pathology of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Neuronal cell death due to oxidative stress may causally contribute to the pathogeneses of these diseases. Therefore, neuroprotective antioxidants are considered to be a promising approach to slow down disease progression. We have investigated different aromatic amine and imine compounds for neuroprotective antioxidant functions in cell culture, and found that these compounds possess excellent cytoprotective potential in diverse paradigms of oxidative neuronal cell death, including clonal cell lines, primary cerebellar neurons, and organotypic hippocampal slice cultures. Aromatic amines and imines are effective against oxidative glutamate toxicity, glutathione depletion, and hydrogen peroxide toxicity. Their mode of action as direct antioxidants was experimentally confirmed by electron spin resonance spectroscopy, cell-free brain lipid peroxidation assays, and intracellular peroxide measurements. With half maximal effective concentrations of 20-75 nM in different neuroprotection experiments, the aromatic imines phenothiazine, phenoxazine, and iminostilbene proved to be about two orders of magnitude more effective than common phenolic antioxidants. This remarkable efficacy could be directly correlated to calculated properties of the compounds by means of a novel, quantitative structure-activity relationship model. We conclude that bridged bisarylimines with a single free NH bond, such as iminostilbene, are superior neuroprotective antioxidants, and may be promising lead structures for rational drug development. PMID- 11767951 TI - Nitric oxide generation in aqueous solutions of cigarette smoke and approaches to its origin. AB - By using the ESR spin trapping technique with the N-methyl-D-glucamine dithiocarbamate (MGD)2-Fe(II) complex, the generation of nitric oxide (NO), a gaseous free radical, was observed in NO spin trapping solution bubbled with the filtered main-stream of cigarette smoke. The ESR signal with a three-line spectrum characteristic of an NO radical, which was not observed immediately after bubbling of smoke, started rapidly increasing with time up to around 25 min after the last addition of ferrous ions Fe(II), and then slowly approached a peak value dependent on the burned cigarette mass and on the smoking speed. The production of NO was, however, much affected by air oxidation and enhanced by the addition of ascorbic acid. A certain concentration of sodium nitrite (NaNO2) solution, in which nitrite NO2- is assumed as the main origin of the NO, mimicked closely the time course of NO generation resulting from the smoke of one cigarette. The cigarette smoke that was passed through alkaline pyrogallol solution as a deoxidizer; however, it exhibited an unchanged intensity of NO signal throughout the measurement. These results strongly suggest that NO would be gradually reproduced from NO2- in the reductive aqueous solution containing excess Fe(II) through NO2, which is initially formed and is concomitantly oxidized from NO in cigarette smoke. PMID- 11767952 TI - A recombinant scFv/streptavidin-binding peptide fusion protein for the quantitative determination of the scorpion venom neurotoxin AahI. AB - We created a construct encoding a peptide known to mimic the binding properties of biotin fused to the carboxy-terminus of a scFv fragment that binds a scorpion toxin (AahI). This fusion protein was produced in the periplasm of bacteria and purified to homogeneity by single-step affinity chromatography on streptavidin agarose with a yield close to 1 mg/l. DNA sequencing, dot blot and mass spectrometric analyses demonstrated the integrity of the soluble immunoconjugate. Fusion to the streptavidin-binding peptide did not affect the ability of the scFv to recognize its antigen with a high affinity (Kd = 2.3 x 10(-10) M). Similarly, the streptavidin-binding property was not impaired in the fusion protein. Thus, the immunoconjugate was bifunctional and had a low molecular mass of 28 kDa. This enabled us to develop rapid and sensitive immunoassays for the specific detection of the toxin AahI accurately to 0.6 ng/ml, opening up new perspectives for the diagnosis of envenomations. PMID- 11767953 TI - Systematic reviews of diagnostic research. Considerations about assessment and incorporation of methodological quality. AB - The aim of this paper is to provide a theoretical background for performing and reading systematic reviews of diagnostic studies. We first discuss items for assessment of methodological quality in diagnostic studies and then present methods on how to incorporate these quality measures in systematic reviews. The items of internal validity determine whether the presented results of the individual studies are unbiased and can be trusted. Items of external validity determine to what extent the results are applicable outside the population in which the study was performed. The issues concern the adequacy of the study population, the performance and interpretation of the diagnostic tests and the presentation of the results. Several methods exist for incorporation of issues of methodological quality into systematic reviews, such as subgroup analyses, meta regression analysis, and methodological scores. Publications of diagnostic studies should provide sufficient information to enable assessment of the methodological quality. Furthermore, publication of results of subgroup analyses should be promoted. Methodological criteria lists might help to improve the quality of systematic reviews of diagnostic research. With the items of methodological quality in mind the general practitioner might be better equipped to critically read and interpret diagnostic reviews. PMID- 11767954 TI - Effects of the frequency of alcohol intake on risk factors for coronary heart disease. AB - A cross-sectional study was conducted in 3660 male workers to examine whether the weekly frequency of alcohol intake affected serum lipids and blood pressure, which are risk factors for coronary heart disease, independently of the weekly alcohol consumption. Information regarding life-style habits and current medication was obtained by questionnaire. The effects of the frequency were examined using Tukey's test in the groups of drinkers divided according to their alcohol consumption. In moderate (189-377 ml/week) drinkers, a higher frequency of drinking was related to a higher level of HDL-cholesterol, and a lower level of triglycerides. In light (1-188 ml/week) and heavy (378-566 ml/week) drinkers, a higher frequency of drinking was also related to a higher level of HDL cholesterol. There were no significant relations between the frequency of drinking and total cholesterol, or blood pressure in these three groups. Similar results were obtained when values were adjusted for age, body-mass index, smoking, physical activity and weekly alcohol consumption. Multiple regression analysis in the whole drinkers also showed that the weekly frequency of drinking was associated with HDL-cholesterol, but not with triglycerides (p = 0.052), total cholesterol, or blood pressure. The results suggest that the weekly frequency of drinking may affect the levels of HDL-cholesterol independently of the weekly alcohol consumption. PMID- 11767955 TI - Haemophilus influenzae type b colonization in children in a hospital-based day care center. AB - We sought to assess the effect of day care center (DCC) attendance and parental health care work environment on the prevalence of Haemophilus influenzae type b (Hib) pharyngeal colonization in children in Turkey. Children of health care workers were evaluated by nasopharyngeal culture specimens obtained prior to enrollment at a hospital-based DCC at Cerrahpasa Medical Faculty (CMF-DCC) and then again after 3 months of attendance. A larger cohort from this same DCC was evaluated after 6 months of attendance and compared to a group of children of non health care workers enrolled in Bahcelievler-DCC. As is standard of care in Turkey, none of these children had received the Hib vaccine. Fifty children of health care workers were evaluated prior to their enrollment and then again after 3 months at CMF-DCC. The incidence of Hib carrier state at enrollment was 4% and increased to 22% after 3 months at the DCC. To assess the affect of parental health care employment on Hib carriage rates, 103 children from CMF-DCC and 40 children of non-medical families at Bahcelievler-DCC were evaluated. Hib carrier state was identified in 40.7 and 47.5% after more than 6 months of attendance at CMF-DCC and Bahcelievler-DCC, respectively. No significant difference was observed between carriage rates of children coming from medical and non-medical families and the average carriage rate was 42.6% when duration of day-care attendance exceeded 6 months. Our results demonstrate that Hib carriage rates are affected by the duration of DCC attendance. Parents' employment in a health care facility does not affect carriage rates. PMID- 11767956 TI - Appearance of methicillin-resistant Staphylococcus aureus (MRSA) sensitive to gentamicin in a hospital with a previous endemic distinct MRSA. AB - Since 1990 a clone of gentamicin and methicillin-resistant Staphylococcus aureus (MRSA) has remained endemic in our hospital, but since January 1996 a gentamicin sensitive strain has progressively replaced the previous clone. We characterized the phenotypic and molecular pattern of the MRSA strains isolated in our hospital in 1996 and compared prospectively the epidemiological, clinical and evolutionary characteristics of ninety patients infected or colonized by gentamicin-sensitive MRSA (GS-MRSA) (49) and by gentamicin-resistant MRSA (GR-MRSA) (41). Finally we studied the variation of aminoglycoside consumption in our hospital from 1989 to 1996. We observed two antibiotypes (GS-MRSA and GR-MRSA) corresponding to two major chromosomal patterns. Patients with GS-MRSA usually acquired the infection 72 hours after hospital admission. No significant differences were observed in epidemiological characteristics, clinical presentation and evolution between patients with GS-MRSA and GR-MRSA. Since 1989 aminoglycoside intake in our hospital has decreased by 46%. PMID- 11767957 TI - Age-incidence relationships and time trends in cervical cancer in Sweden. AB - Age-incidence relationships are informative of carcinogenic mechanisms. These have been previously assessed for cervical squamous cell carcinoma (SCC) but not for adenocarcinoma. The aim was to assess by means of age-, period- and cohort specific analyses and Poisson regression modelling whether the two types of cervical cancer show an age-incidence maximum at a relatively young age, as shown in cross-sectional analyses. The Swedish Family-Cancer Database was used to analyse age-incidence relationships in cervical SCC and adenocarcinoma diagnosed in years 1958-1996, including a total of 15,118 and 1866 cases, respectively. Area of residence and socio-economic status were included in analyses because they were risk factors of cervical cancer. The analysis of cervical SCC confirmed an incidence maximum at ages 35-39 years. The data for adenocarcinoma also suggested a similar early age maximum but the curves differed extensively by birth cohort. The incidence of adenocarcinoma increased substantially at young age groups towards the end of follow-up. Endometrial adenocarcinoma and vaginal and vulvar SCC, which share some risk factors with cervical cancer, did not show an early age incidence maximum. The results also showed that there was a decrease in the incidence of cervical SCC around year 1960, almost 10 years before the organized population screening, probably due to introduced opportunistic pap testing. The benefits of the organized screening were observed as a further decline in the incidence rates. The unique age-incidence relationships in cervical cancer call for biological explanations. PMID- 11767958 TI - Gender and drug treatment as determinants of mortality in a cohort of heart failure patients. AB - AIM: We assessed gender differences in the risk of mortality in heart failure (HF) patients and evaluated the association between HF drug treatment and mortality. METHODS AND RESULTS: We identified a cohort of 820 patients with newly diagnosed HF in 1996 in UK general practices. The diagnosis of HF was confirmed by the general practitioner. Fifty per cent were females and 27% were less than 70 years old. During a mean follow-up of 2 years, 172 patients died. We used computerized records to assess risk factors and drugs prescribed as treatment. The information on severity was assessed through a questionnaire. We performed a nested case-control analysis, and observed that men had twice the risk of dying than females, however the effect of age on mortality was stronger in females than males. We found a similar interaction between HF severity and sex. Data on use of some cardiovascular drugs such as diuretics, beta-blockers ACE-inhibitors and calcium channel blockers were suggestive of a reduced mortality risk. Current use of nitrates and glycosides carried an increased risk. CONCLUSION: Older age, male sex and severity of HF were the main predictors of mortality among HF patients. Long-term use of beta-blockers was associated with a significantly reduced risk of mortality. PMID- 11767959 TI - Cardiovascular risk factors as determinants of 25-year all-cause mortality in the seven countries study. AB - This analysis aims at describing all-cause mortality and their determinants in 16 cohorts of middle-aged men of eight nations. A total of 12,763 men aged 40-59 years were enrolled in the late 1950s and early 1960s in 16 cohorts located in the USA, Finland, The Netherlands, Italy, Croatia, Serbia, Greece and Japan. The highest death rates were found in Slavonia-Croatia, due to high rates of infectious diseases and violence (death rate of 610 per 1000), and in East Finland due to high rates from coronary heart disease (death rate of 597 per 1000). The lowest death rates were found in a highly educated group in Belgrade, Serbia (death rate 295 per 1000) and in Crete, Greece (death rate 314 per 1000). The ecological analysis showed no significant relationship between mean risk factor levels and all-cause death rates except for the direct association with systolic blood pressure during the first 15 years follow-up. Individual multivariate analysis on eight national pools showed that age, systolic blood pressure, and smoking habits are direct, significant, and universal long-term predictors of all-cause mortality. Serum cholesterol, physical activity and body mass index were so only in some areas. Multivariate coefficients were similar across nations. Pooled hazards ratios were 1.55 for a difference of 5 years of age (CI: 1.51-1.59); 1.23 for 10 cigarettes smoked per day (CI: 1.20-1.26); 0.91 for one unit (based on three grades) of physical activity score (CI: 0.87-0.95); 1.04 for 1 mmol/l of serum cholesterol (CI: 1.02-1.07); and 0.93 for three units of body mass index (CI: 0.91-0.96). In conclusion some cardiovascular risk factors predict long-term risk of all-cause mortality in different cultures. PMID- 11767961 TI - Does ethnicity predict lactation? A study of four ethnic communities. AB - Human lactation is influenced by a variety of interrelated factors. The purpose of the study was to see whether the racial/ethnic factor is predictive of the onset of lactation and of the volume of breast milk. We planned a prospective study enrolling 269 women who were classified into four ethnic groups: Group 1 Arabs, Group 2 Africans, Group 3 Eastern Europeans, Group 4 Italians. Data regarding the women's habits, medical history and pregnancy were collected. After delivery we recorded the onset of lactogenesis and volume of milk output up until the fifth post-delivery day. A Cox model was fitted in order to assess the independent role that ethnicity has on the time to lactation; a general linear model was used to relate ethnicity to the overall amount of milk produced. Mean age was 27 years and was similar in all groups; half of the women were primiparae. All babies were exclusively breast-fed. Median time to lactation was 36 hours (20-36) and the median daily amount of milk produced was 173.5 ml (119 215). The earliest onset of lactation and the highest milk output was registered among Arab and Eastern European women. On Cox regression analysis ethnicity appeared to be an independent predictor of earlier lactogenesis: breast milk output occurred significantly earlier in the immigrant population than it did in the Italian population. No difference was observed among the immigrants. The multiple regression model showed that ethnicity independently predicts the overall amount of milk production: the Immigrant population produced a significantly higher milk output than the Italian population. No differences were observed within the immigrant groups. Ethnicity has been shown to be associated with the characteristics of breast-feeding. Further research is needed to understand the underlying mechanism. PMID- 11767960 TI - Do cardiovascular risk factors in men depend on their spouses' occupational category? AB - OBJECTIVE: To analyse the relationships between major cardiovascular risk factors in French men and their spouses' occupational category (OC), taking their own OC into account. DESIGN: A large sample of volunteers working in the French National Electricity and Gas Company (GAZEL). As a check of the robustness, the same analysis was performed in a population-based survey (French multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) registers). SETTING: Any site of the company in France. Representative sample from the population of the three registers (Lille, Strasbourg, Toulouse). PARTICIPANTS: 9486 and 534 men respectively, in working activity, living in couple and aged 40 to 50 years. MAIN OUTCOME MEASURES: Self-reported arterial hypertension, diabetes, hypercholesterolemia, leisure time sedentary lifestyle, smoking status, body mass index (BMI) and alcohol consumption. RESULTS: In the GAZEL study, diabetes, smoking status, and alcohol consumption in men were associated with their own OC. In contrast, spouses' OC was independently associated with men's hypertension, hypercholesterolemia, sedentary lifestyle, and BMI: men whose spouses were unoccupied or workers have higher risk factors levels. In the MONICA study, the results were mostly comparable, at least for hypercholesterolemia, sedentary lifestyle, smoking status and alcohol consumption. CONCLUSION: Spouses' OC was independently associated with several cardiovascular risk factors in men. These results might indicate that socioeconomic status of the couple, and not only individual characteristics, should be taken into account for a better understanding of cardiovascular risk. PMID- 11767962 TI - Characteristics of women exposed and unexposed to environmental tobacco smoke (ETS) in a general population sample of North Italy (Po River Delta epidemiological study). AB - To define qualitative and quantitative categories of exposure to environmental tobacco smoke (ETS) and to assess possible differences for life-style factors between exposed and unexposed women, we studied 867 nonsmoking women (8-73 aged), selected from a general population sample living in the Po Delta area (near Venice, North Italy). Information was collected by a standardized questionnaire. ETS exposure at home, at work or elsewhere was considered. There was a prevalence of ETS exposure of 46% in the whole sample; the rate had a negative association with age. Exposure to ETS occurred more frequently at home, either singly (56%) or in combination with school/work and other places (75%). Exposed women were significantly younger, taller and lighter than those unexposed. Logistic regression on 20+ aged women showed that single-separated-widowed, workers, women living in a rental house, and women with a central forced air heating were significantly more exposed to ETS. Crowding index (n inhabitants/n rooms of the house) was significantly higher in those exposed. These results indicate that ETS exposure is quite frequent in Italian women and that some life-style factors (e.g. marital status or occupational status or some home characteristics), should be considered in the study of relationship between passive smoking and respiratory health. PMID- 11767963 TI - Surgical antibiotic prophylaxis: effect in postoperative infections. AB - OBJECTIVE: to assess the risk of surgical wound infection and hospital acquired infections among patients with and without adequate antibiotic prophylaxis. Also, to provide models to predict the contributing factors of hospital infection and surgical wound infection. DESIGN: survey study. Prospective cohort study over 14 months, with data collected by a nurse and a epidemiologist through visits to the surgical areas, a review of the medical record and consultation with the medical doctor and nurses attending the patients. SETTING: Two hundred and fifty bed, general hospital serving Puertollano (Ciudad Real), population--50,000. RESULTS: between February 1998 and April 1999, 754 patients underwent surgery, 263 (34.88%) received appropriate perioperative prophylaxis while 491 (65.12%) received inadequate prophylaxis. For those who received adequate antibiotic prophylaxis, the percentage of nosocomial infection was 10.65% compared with the group who received inadequate prophylaxis in which the percentage of nosocomial infection was 33.40%. The relative risk of nosocomial infection was, therefore, 4.21 times higher in the latter group (confidence intervals 95%: 2.71-6.51). A patient in the inadequate prophylaxis group had a 14.87% chance of wound infection while a patient in the adequate prophylaxis group had a 4.56% chance of wound infection. The relative risk of wound infection was 3.65 times higher in the group that received inadequate prophylaxis (confidence intervals 95%: 1.95 6.86). The final regression logistic model to assess nosocomial infection incorporated seven prognostic factors: age, length of venous periferic route, vesicle catheter, duration of operation, obesity, metabolic or neoplasm diseases and adequate or inadequate prophylaxis. When we incorporated these variables in the multi-factorial analysis we found that the relative risk of developing nosocomial infection was 2.33 times higher in the group which received inadequate prophylaxis. When we applied the second logistic multiple regression model (wound infection), we discovered that the probability of developing surgical wound infection was 2.32 times higher in the group which received inadequate prophylaxis as opposed to the group, which received adequate prophylaxis. The goodness of fit (Hosmer-Lemeshow test) showed a correct significance in all models. CONCLUSIONS: a multi-factorial analysis was applied to identify the high risk patients and the risk factors for postoperative infections. Through the application of these multiple regression logistic models, we conclude that the correct antibiotic prophylaxis is effective and will subsequently reduce postoperative infection rates, especially in high-risk patients. Therefore, the choice of antimicrobial agent should be made on the basis of the criteria of hospital committee. PMID- 11767964 TI - Antimicrobial utilization and bacterial resistance at three different hospitals. AB - It has been generally recognized that the prevalence of bacterial resistance among bacteria is an unavoidable consequence of antibiotic use and is positively linked to the overall use of antibacterial drugs. The purpose of this study was to investigate the extent of antimicrobial usage and to evaluate the antimicrobial resistance at three different hospital settings in Croatia: a clinical hospital, a general hospital and a specialized clinic for infectious diseases. In this survey the antimicrobial drug consumption and antimicrobial susceptibility test results were analyzed for the first 6 months of 1997 in three different hospitals in Croatia: the University Hospital Center (UHC), Rijeka, the Clinic for Infectious Diseases 'Dr Fran Mihaljevic', Zagreb and the Dubrovnik General Hospital. The data were collected from corresponding hospital pharmacy records and microbiology laboratories. Antimicrobial drug utilization was expressed in number of defined daily doses (DDDs) per 100 bed days. High antimicrobial utilization and high resistance rates were found in all three hospitals. At the Clinic for Infectious Diseases, the most frequently used antimicrobials where those of narrow spectrum while at the UHC Rijeka and the Dubrovnik General Hospital the broad spectrum antimicrobials were mostly used. The highest antimicrobial consumption was noted at the Susak locality of the UHC, Rijeka, where the highest resistance rates of bacteria to antimicrobials were also found. Results of this observational study indicate that attempts should be made to reduce the influence of factors that may lead to emergent resistance. The most effective approach to the prevention of transmission of multidrug-resistant pathogens is preventing the initial emergence of resistance. A rational and strict antibiotic policy is thus of great importance for the optimal use of these agents. PMID- 11767965 TI - Sexual behavior and the prevalence of Chlamydia trachomatis infection in asymptomatic students in Germany and Spain. AB - This study aimed to assess patterns of sexual activity, preventive behaviors, contraceptive use, and the prevalence of chlamydia infection in student populations from two countries. 188 asymptomatic students of the University of Bielefeld, Germany and 590 students of the Navarra Public University, Spain were surveyed using a standardized self-administered questionnaire. Urine samples were analyzed by ligase chain reaction technique for chlamydia infection. Compared to German students, Spanish students were less likely to have more than one sex partner within the last 12 months (OR: 0.62; CI: 0.46-0.83), to have sexual intercourse more than one time per week (OR: 0.70; CI: 0.52-0.93) and to use oral contraceptives (OR: 0.16; CI: 0.10-0.26). They reported a higher use of condoms (OR: 2.93; CI: 2.01-4.27) and were more likely to always use condoms with a new sex partner (OR: 2.47; CI: 1.72-3.53). The prevalence of chlamydia infection was considerably higher in German students (5.8% [corrected] in females; 2.2% in males) than in Spanish students, where no case was found. The higher frequency of sexual activity, a higher engagement in risk-taking sexual behavior and the lower use of barrier contraceptives may contribute to the higher prevalence of chlamydia infection in German students. PMID- 11767966 TI - Ignoring 'downstream infection' in the evaluation of harm reduction interventions for injection drug users. AB - Harm reduction interventions to reduce blood-borne disease incidence among injection drug users (IDUs). A common strategy to estimate the long-term impact of such interventions is to examine short-term incidence changes within a specific group of individuals exposed to the intervention. Such evaluations may overstate or understate long-term program effectiveness, depending upon the relationship between short-term and long-term incidence and prevalence. This short paper uses steady-state comparisons and a standard random-mixing model to scrutinize this evaluation approach. It shows that evaluations based upon short term incidence changes can be significantly biased. The size and direction of the resulting bias depends upon a simple rule. For modest interventions, such analyses yield over-optimistic estimates of program effectiveness when steady state disease prevalence exceeds 50% absent intervention. When steady-state prevalence is below 50%, such analyses display the opposite bias. PMID- 11767967 TI - Neural prostheses in the respiratory system. AB - Approximately 5% of spinal cord-injured individuals suffer from respiratory muscle paralysis and require chronic mechanical ventilation. Unfortunately, this form of life support is associated with a number of undesirable side effects and discomforts. The only available alternative to mechanical ventilation is diaphragm pacing via bilateral phrenic nerve stimulation. This technique can provide patients with marked improvements in life quality and offers significant advantages compared to mechanical ventilation. Many patients, however, do not have bilateral phrenic function or are not willing to accept the risks inherent with phrenic nerve pacing and therefore are not candidates for this technique. Two alternative methods to ventilate patients with ventilator-dependent tetraplegia are reviewed in this paper. In patients with only a single functional phrenic nerve who are therefore not candidates for phrenic nerve pacing, combined intercostal muscle and unilateral phrenic nerve stimulation has recently been shown to maintain ventilatory support. In patients with bilateral phrenic nerve function, on-going studies suggest that intramuscular diaphragm pacing may be a useful alternative to direct phrenic nerve pacing. With the electrodes placed into the diaphragm laparoscopically, this method allows for the diaphragm to be activated without manipulation of the phrenic nerve, need for thoracotomy, or hospitalization. Both techniques provide benefits similar to that derived from bilateral phrenic nerve pacing and hold promise as alternative methods of ventilatory support in selected populations groups. PMID- 11767968 TI - Preliminary performance of a surgically implanted neuroprosthesis for standing and transfers--where do we stand? AB - This paper describes the preliminary performance of a surgically implanted neuroprosthesis for standing and transfers after spinal cord injury (SCI) in an initial group of 12 volunteers with longstanding paralysis. The CWRU/VA standing neuroprosthesis consists of an 8-channel implanted receiver-stimulator, epimysial and surgically implanted intramuscular electrodes, and a programmable wearable external controller. After reconditioning exercise and rehabilitation with the system, most individuals with paraplegia or low tetraplegia were able to stand, transfer, and release one hand from a support device to manipulate objects in the environment or to perform swing-to ambulation in a walker. The effort and assistance required for transfers were reduced for users with mid-level tetraplegia, although the maneuvers were not independent. Neuroprosthesis users with tetraplegia and paraplegia alike benefited from the improvements in their general health derived from exercise, including reduced risk of decubiti and self reported modulation of spasticity. Stimulated responses are stable and sufficiently strong for function, and implanted components are reliable with a 90% probability of epimysial electrode survival at 4 years post-implant. The techniques employed are repeatable and teachable, and suitable for multi-center clinical trial. PMID- 11767969 TI - Model-based development of neuroprostheses for restoring proximal arm function. AB - Neuroprostheses with the use of functional neuromuscular stimulation (FNS) have the potential to restore elbow and shoulder function lost to paralysis because of spinal cord injury (SCI). The human shoulder is highly flexible and thus provides a large range of motion to the arm and hand, although at the expense of precarious stability of the articulations. The complexity of the shoulder has prevented widespread use of FNS at this joint. However, musculoskeletal modeling of the elbow and shoulder has the potential to significantly speed the development of neuroprostheses by allowing many mechanical issues to be resolved in simulation prior to implementation in human subjects. This paper describes our rationale for the use of musculoskeletal modeling, the model we are using, and several practical applications of the model to study the potential use of shoulder and elbow muscle FNS to restore function following cervical SCI. PMID- 11767970 TI - Stabilizing electrode-host interfaces: a tissue engineering approach. AB - The stability of implanted electrodes is a significant problem affecting their long-term use in vivo. Problems include mechanical failure and inflammation at the implantation site. The engineering of bioactive electrode coatings has been investigated for its potential to promote in-growth of neural tissue and reduce sheer at the electrode-host interface. Preliminary results indicate that hydrogel coatings with either collagen I or polylysine-laminin-1 can promote cortical nerve cell attachment and differentiation on silicon substrates. Additionally, slow-release microtubules can also be implanted in these gels to release agents that either provide trophic support to neurons or prevent inflammation locally. When silicon discs are coated with collagen type I, the coating remains stable for 55 days. Further testing is underway, but initial results indicate that tissue-engineering approaches provide useful insights to help address the problem of host-electrode instability in the brain. PMID- 11767971 TI - At the interface: convergence of neural regeneration and neural prostheses for restoration of function. AB - The rapid pace of recent advances in development and application of electrical stimulation of the nervous system and in neural regeneration has created opportunities to combine these two approaches to restoration of function. This paper relates the discussion on this topic from a workshop at the International Functional Electrical Stimulation Society. The goals of this workshop were to discuss the current state of interaction between the fields of neural regeneration and neural prostheses and to identify potential areas of future research that would have the greatest impact on achieving the common goal of restoring function after neurological damage. Identified areas include enhancement of axonal regeneration with applied electric fields, development of hybrid neural interfaces combining synthetic silicon and biologically derived elements, and investigation of the role of patterned neural activity in regulating various neuronal processes and neurorehabilitation. Increased communication and cooperation between the two communities and recognition by each field that the other has something to contribute to their efforts are needed to take advantage of these opportunities. In addition, creative grants combining the two approaches and more flexible funding mechanisms to support the convergence of their perspectives are necessary to achieve common objectives. PMID- 11767972 TI - Emerging clinical applications of electrical stimulation: opportunities for restoration of function. AB - Emerging clinical application of electrical stimulation in three systems is reviewed. In the bladder, stimulation of sacral posterior roots reduces reflex incontinence and significantly improves bladder capacity. With the combination of anterior and posterior root stimulation, bladder control can be achieved without the need for rhizotomy. Preliminary research demonstrates that bladder contractions may also be generated by stimulation of the urethral sensory branch of the pudendal nerve, even after acute spinal cord transection, while inhibition of the bladder and control of urge incontinence can be achieved by stimulation of the whole pudendal nerve. Spinal cord stimulation can modulate the activity of the intrinsic cardiac nervous system involved in the regulation of regional cardiac function and significantly reduce the pain associated with angina pectoris. Finally in the area of upper airway disorders, functional electrical stimulation has great potential for increasing life support as well as for quality of life in chronic ailments, particularly obstructive sleep apnea and dysphagia. PMID- 11767973 TI - Neuroprosthesis consumers' forum: consumer priorities for research directions. AB - The purpose of this forum was to discuss with consumers having spinal cord injury what their research priorities would be for the field of functional electrical stimulation (FES) and to explore the impact of technology in the lives of people with disabilities. Both FES users and nonusers were included on the panel. The format for the discussion was primarily question and answer, with each participant giving his or her personal response to the moderator's question. Consumer research priorities depended on the individual and his or her personal priorities, preferences, background, history, and level of injury. Common themes that emerged were independence, ease of movement, ease of control, and spontaneity. From the consumers' perspective, the focus of research to restore function ought to be based on the needs and desires of the consumer, not just on the scientifically intriguing aspects of a particular technology. PMID- 11767974 TI - Introduction to the single-topic issue on functional electrical stimulation. PMID- 11767975 TI - Deep brain stimulation: challenges to integrating stimulation technology with human neurobiology, neuroplasticity, and neural repair. PMID- 11767976 TI - Decision-making, dementia and the law: cross national perspectives. PMID- 11767977 TI - Legal interventions for persons with dementia in the USA: ethical, policy and practical aspects. AB - The US legal system has developed a number of methods by which the state or private parties may intervene to protect persons, including those with dementia, who lack sufficient cognitive or emotional capacity to make and express autonomous choices about various aspects of their lives. These interventions may be planned and voluntary or unplanned and involuntary. This article explores the ethical and cultural values underlying legal alternatives in the United States and their strengths and weaknesses when measured against those values. The article poses issues about which US policy makers, health and human service practitioners, and attorneys might seek wisdom from the various strategies that other countries have devised to deal with the challenge of protecting, but not overprotecting, their own citizens with dementia. PMID- 11767978 TI - Perspectives on legislation relating to the rights and protection of people with dementia in Europe. AB - This article focuses on the main legal provisions in Europe relating to the protection and rights of people with dementia. The information referred to was obtained in the framework of two EC funded projects, which involved the collection, translation and comparison of relevant legislation, and then the writing of legal recommendations to improve the legal rights and protection of people with dementia. The first project started in 1997 and was completed in 1999. The second project started in 1999 and was completed in November 2000. The article provides an overview of the main features of some of the laws in Europe on a few key issues, i.e. guardianship, coercive measures and bioethical issues. Some of the main differences between the systems in different countries are highlighted. An attempt is made to show how the adequacy and appropriateness of legal provisions differ vastly from one country to the next and also to identify the emergence of a few trends, which seem to reflect a movement towards a greater awareness of the nature of mental incapacity and hence a better provision for the rights and protection of people with dementia. PMID- 11767979 TI - Empowerment and decision-making for people with dementia: the use of legal interventions in Scotland. AB - Dementia is associated with a decline in the ability to reason and make judgements thereby affecting a person's ability to make sound decisions. Others are not legally entitled to make these decisions until they have been assigned legal jurisdiction to do so. It is not clear, however, the extent to which people with dementia rely on available legal interventions. The growing emphasis on early diagnosis for people with dementia provides an opportunity for people to plan and control decisions about financial management and welfare and may well lead to an increase in the uptake of these interventions. This paper coincides with a move to reform outdated Scottish Law with the Adults with Incapacity (Scotland) Act 2000. This legislation proposes a more integrated and flexible approach to the legal management of the affairs of people with reduced decision making capability. The paper reviews of the recent literature on the use of legal interventions for people with dementia and their families, and discusses the empowering or disempowering nature of the interventions. PMID- 11767980 TI - The law and dementia--issues in England and Wales. AB - This paper reviews the proposals from the Lord Chancellor's Department for new Mental Incapacity law for England and Wales as they may impact on older people with dementia. Various concerns and issues are raised, particularly from the perspective of health care professionals, and the focus is the interface between such issues and the day-to-day clinical realities for a specialist team dealing with old people with dementia. A brief overview of where problems have arisen with the law in recent times is put in the context of the political/legal structures in England and Wales PMID- 11767981 TI - The prevalence and correlates of capacity to consent to a geriatric psychiatry admission. AB - In the UK the recent House of Lords ruling on the Bournewood case provided a statutory basis for admitting patients into psychiatric beds who lack the capacity to consent, but do not dissent, without recourse to detention under the Mental Health Act. A study to ascertain the prevalence and correlates of the lack of capacity to consent to geriatric psychiatry inpatient admission was undertaken. All consecutive acute inpatient admissions to a geriatric psychiatry unit over a six-month period were examined by an independent research psychiatrist (SM). Data on demography, diagnosis, severity of cognitive impairment, insight, the SM's assessment of capacity to consent to the admission and the consultant psychiatrists' assessment of the capacity to consent to the admission were ascertained. The overall prevalence of lack of capacity to consent to geriatric psychiatry inpatient admission was 48%. It was associated with a diagnosis of dementia, increased severity of cognitive impairment, reduced insight and detention under the Mental Health Act. The kappa concordance between SM's and the consultant psychiatrist's assessment of capacity was modest at 0.6. These findings require replication in a larger multi-centre study, perhaps using standardised instruments to measure capacity. A large number of psychiatric patients are informally admitted despite lacking the capacity to consent to the admission because they do not dissent. These patients do not enjoy the safeguards available under the Mental Health Act. PMID- 11767982 TI - Should a diagnosis of Alzheimer's disease be disclosed? AB - There is evidence that some health practitioners may be reluctant to disclose a diagnosis of Alzheimer's disease (AD) to patients. However, this reluctance towards disclosure may not be in accordance with patient expectation. This study examined the attitudes of 100 undergraduate psychology students towards disclosure practices in relation to AD, before and after exposure to AD education. After AD education, 93% of participants indicated a desire to be informed of a diagnosis of AD, and 95% of participants were in favour of telling a close relative a diagnosis of AD. Results are discussed in terms of the relationship between age and attitudes towards AD diagnosis. It is concluded that the high rate of support for disclosure of AD diagnoses to patients among younger adults may reflect a change in the information preferences of patients brought about by a shift away from a patriarchal medical model, toward a more autonomous model of health. PMID- 11767983 TI - Anxiety sensitivity, anxiety, and depression in older patients and their relation to hypochondriacal concerns and medical illnesses. AB - This study examined the role of anxiety sensitivity (the fear of anxiety symptoms because such symptoms are believed to have harmful consequences), anxiety, and depression in older adults and their relation to hypochondriacal concerns and medical illnesses. The sample included 53 clinic-referred (M age = 78.8 years), and 53 non-clinic referred (M age = 70.9 years) older adults. It was examined whether (1) anxiety sensitivity was elevated in the clinic-referred group relative to the non-referred group, (2) symptoms of anxiety, anxiety sensitivity and depression were related to number of medical illnesses and/or to hypochondriacal concerns, and (3) anxiety sensitivity was a better predictor of hypochondriacal concerns relative to depression or trait anxiety. The results indicated that anxiety sensitivity was significantly elevated in the clinic referred group relative to the non-clinic referred group, was negatively associated with history of medical illnesses, was strongly associated with hypochondriacal concerns, and was a better predictor of hypochondriacal concerns than depression and trait anxiety. The findings are discussed in terms of problems facing older adults as they relate to the constructs of anxiety sensitivity and hypochondriacal concerns. PMID- 11767984 TI - The impact of the native language of Alzheimer's disease and normal elderly individuals on their ability to recall digits. AB - Recent studies have indicated that Spanish-speaking Alzheimer's disease (AD) patients perform more poorly than English-speaking patients on the Digit Span subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). In the current investigation, the performance of English-speaking and Spanish-speaking Alzheimer's disease patients (N = 119) and normal elderly controls (N = 91) were compared with regards to their capacity to remember digit strings of different lengths. Subjects were administered the standard version of the Digit Span subtest of the WAIS-R as well as a modification of the test (chunking task) in which the numbers were presented in pairs (e.g. 27, 41, 46, 12, etc.). Results indicated that both English-speaking groups, AD patients as well as normal controls, had significantly higher scores on all aspects of the standard Digit Span tasks relative to their Spanish-speaking counterparts (forward, backward, and total scores). In contrast, English-speaking and Spanish-speaking AD groups did not differ with regards to their performance on the two digit chunking task forward score. Similar performance on all aspects of the chunking task was evidenced in the English-speaking and Spanish-speaking normal elderly control groups. These findings have important implications for the development of more culture and language appropriate cognitive test batteries for AD patients and the normal elderly. PMID- 11767985 TI - Spiritual healing in elderly psychiatric patients: a case-control study in an Egyptian psychiatric hospital. AB - In some cultures, mental illness and its treatment may be closely linked to beliefs relating to sin, suffering, and separation from the divine, or even possession by evil. The aim of this study was to explore whether there was an association between receiving spiritual healing and the occurrence of schizophrenic relapses in a sample of elderly Egyptian patients. The method used was a case-control study, comparing patients with an ICD 10 diagnosis of schizophrenia who received spiritual healing and those without spiritual healing, in terms of the occurrence of relapses during a specified period. Patients who received spiritual healing relapsed more frequently than those who did not (adjusted OR 3.5 p < 0.05). Relapse was also associated with age and certain methods of healing. The risk of relapse was independent of gender, duration of illness and type of religion. The study found spiritual healing to be positively associated with relapse of schizophrenia in a sample of elderly Egyptian patients. It is however difficult to ascertain that the relapse actually started after the process of spiritual healing and not before it. The study findings may suggest that religious history, at least in some cases, should be taken into consideration when planning future management. PMID- 11767987 TI - The onset and alleviation of learned helplessness in older hospitalized people. AB - The objective of this study was to investigate the relevance of learned helplessness (LH) and learned mastery (LM) theories in the respective development of dependence and independence in older hospitalized people. A two-staged experiment was performed. In stage I, meal-related responses of patient participants (n = 84) were automatically completed by a researcher during two consecutive mealtime events (LH induction). LH effects were then assessed by evaluating participant performance during a controllable meal-task and a non-meal related psychomotor task. In stage II, "helpless" participants (n = 35) were then given an expectation of future control over the mealtime event followed by two further meals during which the researcher provided no active assistance (LM induction). LM effects were assessed as in stage I. Participants exposed to the LH inducing strategy demonstrated LH effects within both the meal and psychomotor tasks. These effects were alleviated through exposing participants to the LM inducing intervention. Exposing older hospitalized people to uncontrollable or disempowering circumstances may potentially lead them to develop a LH induced dependence. This may be alleviated by increasing patient's expectation of control leading to the development of LM. PMID- 11767986 TI - Development of a screening instrument for language in older people (Barnes Language Assessment). AB - Language changes are associated with several types of age-related degenerative processes and are known to be particularly stressful for carers. Managing language and communication difficulties in older people has been shown to be an important aspect of dementia care. A test such as the one described here, might be a useful tool for health professionals planning care for older people with possible diagnoses of dementia. The information gained could be used as part of multi-disciplinary team assessment. This paper describes the development of a clinically viable assessment tool for the assessment of language and associated cognitive skills in the older population. Data on 43 normal older people were used to establish preliminary means and lower normal limits, as a guide to distinguishing performance associated with normal age-related change from performance associated with pathology. In the next phase data was collected from 43 older people with possible dementia who were attending clinics and hospital departments. The results suggest that the Barnes Language Assessment can profile language skills and difficulties and may be a useful diagnostic tool to contribute to language assessment of older people. Indications for further research are discussed. PMID- 11767988 TI - Psychometric evaluation of a brief geriatric depression screen. AB - This article is a psychometric evaluation of the experimental Geriatric and Extended Careline Depression Screen (GEDS) for geriatric nursing care residents. The GEDS is a five-item depression screen based on an abbreviated version of the Center for Epidemiological Studies Depression Scale (CES-D). A total sample of 91 male residents over the age of 60 were recruited from a Veterans Administration Nursing Home Care Unit. The Geriatric Depression Scale-Short Form (GDS-SF) was used as a gold standard test to examine the convergent validity of the GEDS. The Discriminant Trait Inventory was used to assess divergent validity and the confounding effects of method variance in this research design. Test-retest reliability, redundance and omission in item content validity were systematically evaluated. A receiver operating characteristics (ROC) curve was used to identify the most effective cut-off score for clinical selection. Reliability was significant, but moderate. Convergent validity with the Geriatric Depression Scale was high. No items were identified as redundant. A review of literature suggested that irritability is an important factor of geriatric depression that had not been included in the original screen. The inclusion of an experimental item to assess irritability, however, did not improve the psychometric properties of the GEDS. PMID- 11767989 TI - Coronary revascularization in Japan. Part 1: survey of facilities during 1997. AB - Coronary artery disease is one of the major causes of morbidity and mortality in industrialized countries, including Japan. Increasing numbers of patients have been treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), but there is little information in Japan concerning the use of revascularization therapy and the facilities. The Japanese Coronary Intervention Study (JCIS) Group conducted a nationwide survey on coronary revascularization procedures and facilities during 1997. A questionnaire was mailed to the presidents or designated delegates of 8,253 laboratories in 7,986 hospitals that had departments of internal medicine and/or cardiovascular medicine and to 578 facilities in 558 hospitals identified by the PCI survey as performing CABG and/or registered in the annual survey carried out by the Japanese Association for Thoracic Surgery. A total of 109,788 PCIs were performed at 1,023 laboratories, and 17,667 CABGs at 477 facilities. PCI and CABG numbers per 10(6) population were 870 and 140, respectively. The ratio of PCI to CABG was 6.2. The numbers of PCI laboratories and CABG facilities per 10(6) population were 8.1 and 3.8, respectively. The majority of PCI laboratories and CABG facilities had a small annual volume: 44% of PCI laboratories and 77% of CABG facilities had annual volumes of 50 or less. Only half of the PCI laboratories had surgical backup on-site. Despite the small volume for each facility, coronary revascularization, especially PCI, is highly utilized in Japan. PMID- 11767990 TI - Coronary revascularization in Japan. Part 2: comparison of facilities between 1997 and 1999. AB - A nation-wide survey on the procedures and facilities of coronary revascularization, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) conducted by the Japanese Coronary Intervention Study (JCIS) group during 1997 revealed that PCI is more often used than CABG and is mainly carried out in low-volume facilities without surgical backup. The present study aimed to investigate the temporal changes in the usage of revascularization therapies and facilities from 1997 to 1999. A questionnaire was mailed in 1998 to the delegates of 1,086 PCI and 582 CABG facilities identified by the previous survey, and 89% of PCIs surveyed and 94% of CABGs surveyed reported back. The number of PCI procedures had increased by 19% from 97,831 to 116,479 and that of CABG procedures also increased by 21% from 16,374 to 19,846. The ratio of PCI to CABG was 5.9 in 1999, showing no significant change from 6.0 in 1997. In parallel, the number of PCI and CABG facilities increased from 888 to 941 and from 442 to 453, respectively. The use of coronary stents and other interventional devices increased during these 2 years. Coronary stents were used regardless of the annual procedural volume of the facilities, whereas other interventional devices, directional and rotational coronary atherectomy, were used mainly in the high-volume laboratories (p<0.01). Beating-heart, off-pump CABG had increased from 2% to 11% of total cases. Continued monitoring of trends in PCI and CABG facilities and procedures will be needed for nation-wide assessment of the use of new technology. PMID- 11767991 TI - Comparison of glucose-insulin-thallium-201 infusion single photon emission computed tomography (SPECT), stress-redistribution-reinjection thallium-201 SPECT and low dose dobutamine echocardiography for prediction of reversible dysfunction. AB - The usefulness of glucose-insulin-thallium-201 (GI-Tl) infusion single photon emission computed tomography (SPECT) in predicting reversible dysfunction has not been evaluated, so the present study recruited 20 patients with regional ischemic dysfunction for investigation. All patients underwent GI-Tl SPECT, post-stress Tl reinjection imaging and low dose dobutamine echocardiography. The diagnostic accuracy of these 3 techniques in predicting functional recovery was evaluated by receiver operating characteristic (ROC) analysis. In segments with functional recovery, regional Tl activities of GI-Tl SPECT were significantly higher than those of reinjection imaging (p<0.05), although there were no significant differences in segments without recovery. The area under the ROC curve for GI-Tl SPECT (0.75+/-0.06) was greater than that for reinjection imaging (0.68+/-0.07). The optimal cutoff values to identify viable myocardium were considered to be 55% of peak activity for GI-Tl SPECT and 50% for reinjection imaging. At this cutoff point, the sensitivity and specificity for detection of functional recovery were, respectively, 85% and 61% for GI-Tl SPECT, and 73% and 61% for reinjection imaging. Dobutamine echocardiography had the same sensitivity (85%), but lower specificity (48%) than GI-Tl SPECT. Continuous infusion of GI-Tl solution enhances regional Tl uptake compared with conventional post-stress reinjection imaging. This study suggests that GI-Tl SPECT is superior to reinjection imaging and dobutamine echocardiography in predicting functional recovery after ischemic left ventricular dysfunction. PMID- 11767992 TI - Clinical characteristics of rapid atrial fibrillation preceding ventricular tachycardia. AB - Spontaneous degeneration of rapid atrial fibrillation (AF) to ventricular fibrillation has been documented in patients with hypertrophic cardiomyopathy (HCM) and Wolff-Parkinson-White (WPW) syndrome. However, the importance of rap PMID- 11767994 TI - Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava. AB - The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25 mm above the atriocaval junction) and the lower posterior aspect of the SVC (17 mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia. PMID- 11767993 TI - Stress-induced ST-segment elevation following myocardial infarction and its role in wall motion abnormality, myocardial ischemia and viability: comparison of response to exercise, dobutamine and dipyridamole. AB - Stress-induced ST-segment elevation following myocardial infarction (MI) has been correlated with myocardial ischemia, viability and wall motion abnormality, but its mechanism is still unclear, so the present study compared ST-segment elevation and wall motion response during exercise, dobutamine and dipyridamole stresses. Twenty-five patients with their first anterior MI underwent exercise, dobutamine and dipyridamole echocardiography on different days 4-6 weeks after MI. Left ventricular wall motion was analyzed using 5-grade/16-segment model and myocardial ischemia was considered as a worsening of the wall motion score index (WMSI) during the stress test; myocardial viability was defined as a reduction of WMSI during low dose dobutamine. Dyskinesis formation was defined by visual analysis as akinesis that became dyskinetic or if the dyskinesis worsened. Both exercise and dobutamine induced ST-segment elevation, but dipyridamole did not. There was no significant difference in the degree of ST-segment elevation between the patients with and without myocardial ischemia or dyskinesis formation. Exercise induced a higher ST-segment elevation in patients with myocardial viability than those without (0.17+/-0.09 mV vs 0.09+/-0.07 mV, p<0.05). Exercise induced ST-segment elevations correlated with dobutamine-induced ST-segment elevations (p<0.01), changes in heart rate (p<0.05) and systolic blood pressure (p<0.05). In conclusions, stress-induced ST-segment elevation does not correlate with either myocardial ischemia or stress-induced dyskinesis, but may be associated with myocardial viability. PMID- 11767995 TI - Relationship between cardiac 123I-metaiodobenzylguanidine imaging and the transcardiac gradient of neurohumoral factors in patients with dilated cardiomyopathy. AB - Cardiac sympathetic nervous function is altered in congestive heart failure (CHF) and the uptake and washout rate of cardiac 123I-metaiodobenzylguanidine (MIBG) are useful markers for evaluating the severity of it. To assess what parameters predict decreased uptake or increased washout rate of MIBG, the concentrations of neurohumoral factor in both the aorta (Ao) and coronary sinus (CS) were measured, as well as hemodynamic parameters by catheterization, in patients with dilated cardiomyopathy (DCM). MIBG imaging was performed within 1 week of cardiac catheterization. Regarding MIBG parameters, the correlation with the transcardiac gradient of norepinephrine (NE), brain natriuretic peptide (BNP) and hemodynamics was investigated. Stepwise multivariate regression analysis was used to determine which variables closely correlated with cardiac MIBG parameters. There was a significant increase in the NE level between the Ao (446 pg/ml) and the CS (727 pg/ml). According to stepwise multivariate regression analysis, the heart/mediastinum (H/M) ratio independently correlated with the transcardiac gradient of BNP (r=-0.480, p<0.01), and the washout rate independently correlated with the transcardiac gradient of NE (r=0.481, p<0.01). These findings indicate that the H/M ratio may reflect the transcardiac gradient of BNP, which implies the degree of left ventricular dysfunction and/or damage and the washout rate may reflect altered cardiac sympathetic nerve terminal in DCM patients with CHF, suggesting that both the H/M ratio and washout rate provide important information about the failing ventricle. PMID- 11767996 TI - Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs. AB - The aim of this study was to use fast Fourier transform analysis to clarify the characteristics of human atrial fibrillation (AF) waves with respect to the duration of AF and the effect of class I antiarrhythmic drugs. Twenty-two patients (10 paroxysmal AF, 12 persistent AF) without organic heart disease were studied by conventional electrophysiological methods. Electrograms were recorded from the right atrial free wall during AF and spectral analysis was performed for 35s (16 consecutive 4096-ms epochs with 50% overlap) and the fibrillation cycle length (FCL) was calculated from the peak frequency. Mean FCL and SD were determined from 16-epoch data, and the temporal variability of FCL was defined as the SD of FCL. Paroxysmal AF had a longer mean FCL than persistent AF (178+/-26ms vs 139+/-16 ms, p<0.001) and AF duration had a significant inverse correlation with mean FCL (r=-0.79, p<0.001). The temporal variability of FCL was significantly greater in paroxysmal AF than in persistent AF (p<0.05) and there was a significant positive correlation between the mean FCL and the temporal variability of FCL (r=0.66, p<0.001). In 8 of 18 patients given a class I antiarrhythmic drug (cibenzoline or procainamide), AF was terminated and in those patients the mean FCLs before administration of class I drugs were significantly greater than in patients without AF termination. With respect to mean FCL before drug administration, conversion occurred in 100% of patients with FCL > or =168 ms and in 17% of those with FCL <168 ms. A longer duration of AF shortens the mean FCL, which is consistent with atrial electrical remodeling. Class I drugs prolong the mean FCL above a critical level and will terminate AF, which can be estimated from the mean FCL before drug administration. PMID- 11767997 TI - Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina. AB - It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA. PMID- 11767998 TI - Subthreshold stimulation in three types of reentrant supraventricular tachycardia: correlation with the results of catheter ablation. AB - The effects of subthreshold stimulation (STS) by direct current were investigated in 20 patients with atrioventricular nodal reentrant tachycardia (AVNRT), 27 with atrioventricular reentrant tachycardia (AVRT) and 3 with idiopathic atrial reentrant tachycardia (IART) STS was delivered to each eligible site for ablation prior to radiofrequency application. STS was defined as 'positive' if it could terminate the tachycardia or disrupt the conduction of accessory pathways without myocardial capture and defined as 'negative' if it could not. Radiofrequency ablation was performed irrespective of a positive or negative result from STS and was successful in all 50 patients. Among the 50 successful ablation sites, STS was positive at 26 sites (11 sites in AVNRT, 12 in AVRT and 3 in IART). STS was positive at 4 sites where ablation failed in 3 patients with AVRT and was negative at 8 sites where ablation was successful in 4 patients with AVNRT and 4 with AVRT. The positive and negative predictive value of STS for the detection of the optimal ablation site were, respectively, 100% and 74% in AVNRT, 73% and 72% in AVRT, and both 100% in IART STS-guided mapping is a specific method to predict the successful catheter ablation of reentrant supraventricular tachycardia. PMID- 11767999 TI - Improving glucose metabolism and/or sarcoplasmic reticulum Ca2+-ATPase function is warranted for immature pressure overload hypertrophied myocardium. AB - The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week old pressure overload hypertrophied rabbit hearts in response to dobutamine by (1) serial echocardiograms in vivo and (2) isolated Langendorff perfusion. Cytosolic Ca2+([Ca2+]i) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose +/- pyruvate was also evaluated. Both systolic and diastolic [Ca2+]i tended to be higher and diastolic calcium removal (tauCa) significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved tauCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca2+]i as well as a slower tauCa. Pyruvate completely preserved myocardial function and [Ca2+]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca2+]i, slower tauCa and reduced sensitivity of the contractile proteins to Ca2+. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism. PMID- 11768000 TI - Differences in the expression of protein kinase C isoforms and its translocation after stimulation with phorbol ester between young-adult and middle-aged ventricular cardiomyocytes isolated from Fischer 344 rats. AB - It is known that the tolerance against ischemia-reperfusion and the effects of preconditioning decrease in aged hearts, but the mechanisms responsible for this diminished ischemic tolerance and reduced efficacy of preconditioning remain unknown. To determine the age-related changes in these mechanisms, protein kinase C (PKC) isoform expression and its translocation by phorbol ester were analyzed because PKC is believed to be involved in preconditioning. Immunoblotting and immunostaining analysis were performed with isoform-specific PKC antibodies using cardiomyocytes isolated from young-adult (12-week-old: 12W) and middle-aged (50 week-old: 50W) Fischer 344 rats. There was significantly greater PKC-delta expression in both the cytosolic and membrane fractions of 12W cardiomyocytes than in 50W ones. Exposure of cardiomyocytes to 100 nmol/L 4-beta-phorbol 12 myristate 13-acetate (PMA) caused translocation of PKC-delta from the cytosol to the membrane in the 12W group, whereas in the 50W group, the translocation was attenuated. Immunostaining confirmed the PKC-delta translocation in the 12W cardiomyocytes. Oil pellet examination showed that the translocation of PKC-delta induced by preconditioning was associated with cell protection from ischemic injury in the 12W group only. Age-related changes in PKC isoform expression and activation in cardiomyocytes might be responsible for the reduced ischemic tolerance and less efficient preconditioning that accompanies aging. PMID- 11768001 TI - Vagal stimulation prior to atrial rapid pacing protects the atrium from electrical remodeling in anesthetized dogs. AB - Atrial electrical remodeling is thought to be the cause of the maintenance of atrial fibrillation (AF). Although the initiation and maintenance of AF is partially associated with autonomic nervous tone, vagally mediated AF does not tend to become permanent. Therefore, the effects of preceding vagal stimulation (VS) on the atrial effective refractory period (ERP) under electrical remodeling conditions were investigated in anesthetized dogs. Atrial ERPs were measured at 5 sites before and after a 7-h period of atrial rapid pacing in the control group. In the VS group, the vagus nerve was stimulated for 20 min before a period of atrial rapid pacing. Atrial rapid pacing shortened the ERP at each site in the control group (electrical remodeling). On the other hand, atrial rapid pacing after VS did not shorten the ERP at any site in the VS group. Tetrodotoxin, which was administered into the fatty tissue overlying the right atrial side of the right pulmonary vein junctions, blocked the protective effect of VS against the shortening of the ERP induced by atrial rapid pacing. In contrast, atropine did not interfere with such protective effects. These results suggest that VS prior to atrial rapid pacing protects the atrium from atrial electrical remodeling. PMID- 11768002 TI - Th1/Th2 balance alteration in the clinical course of a patient with acute viral myocarditis. AB - Cytokines have an important role in the pathogenesis and pathophysiology of myocarditis. In this study, subsets of peripheral helper T lymphocytes (Th) in a patient with acute viral myocarditis were analyzed by 3-color flow cytometry. During the clinical course of myocarditis, the Th1/Th2 ratio of peripheral lymphocytes changed. Th1 was dominant in the acute inflammatory phase during which levels of creatine kinase (CK) increased (day 6), then Th2 levels overtook those of Th1 in the recovery phase during which levels of CK decreased (day 13 and 20). At the time of discharge (day 35), Th1 and Th2 had normalized. Thus, it was speculated that the induction of lymphocytic myocarditis was associated with Th1 dominant status, and recovery was related to Th2 polarity. Th subset imbalances may play an important role in the pathogenesis of acute viral myocarditis and these analyses may be useful for understanding the disease activity of myocarditis. PMID- 11768003 TI - 'No-Touch' isolation procedure for ruptured mycotic abdominal aortic aneurysm. AB - The present study reports a case of the successful surgical repair of a ruptured infra-renal mycotic abdominal aorta with Enterobactor cloacae in a 66-year-old man. During the operative procedure, an extra-anatomic bypass was installed before the laparotomy in order to avoid bacterial contamination. A complete resection of the infected aorta, tapering of the arterial stumps, wrapping of the omentum, and ligation of the aorta and arteries with Teflon tapes was carried out. The patient is alive and well 1 year postsurgery. PMID- 11768004 TI - Spontaneous onset of torsade de pointes in long-QT syndrome and the role of sympathovagal imbalance. AB - The net effects of sympathetic and vagal activity on the QT interval and the mode of spontaneous onset of torsade de pointes (TdP) are still unclear in long-QT syndrome. Two patients with long-QT syndrome had syncope while undergoing Holter ECG investigation. The spontaneous onset of TdP in these patients was analyzed with respect to the relation between the RR and QT intervals. Both patients were high-school students (16- and 17-year-old boys) who had been diagnosed as long-QT syndrome and followed up without medical treatment because they had had neither a history of syncope nor arrhythmia induction by treadmill exercise tests. The first episode of syncope in both patients occurred during ordinary daily life and was not related to exercise or psychological stress. The dynamic changes between the RR and QT intervals associated with the spontaneous onset of TdP were analyzed by Holter ECG. Both patients showed sinus tachycardia followed by abrupt sinus bradycardia immediately before the onset of TdP. The enhanced rate of the adaptive response of the QT interval that occurred during the deceleration of the heart rate preceded the onset of TdP. These observations suggest that the complex situation that follows sympathovagal imbalance may have an important role in the dynamic change in the QT interval and initiation of TdP in patients with long-QT syndrome. PMID- 11768005 TI - Vasospastic total occlusion at the left main tract in a single coronary artery. AB - A 64-year-old man was admitted to hospital under the suspicion of unstable angina pectoris. Coronary angiography showed that he has a single coronary artery originating from the right coronary artery (RCA) without significant fixed stenosis. Acetylcholine was superselectively infused into the left main coronary artery (LMCA), and confirmed the coronary vasospastic occlusion associated with chest pain and elevation of the ST-segment in the precordial leads. This is the first report of the induction of a totally occlusive spasm of the LMCA of a patient with a RCA type single coronary artery, and this case suggests that spasm of the aberrant coronary artery is a potential mechanism for sudden death in patients with a single coronary artery. PMID- 11768006 TI - Surgical experience with management of vascular injuries. AB - To highlight the problems that are associated with the causes, diagnosis and management of vascular injuries. MATERIALS AND METHODS: A retrospective study of 52 cases of vascular injuries managed at the Jos University Teaching Hospital (JUTH) during a ten year period. RESULTS: The sex ratio M:F was 6:1 and the mean age at presentation was 23 years. The most common causes of vascular injuries were road traffic accidents in 44 per cent, iatrogenic 27 per cent and industrial in 13 per cent. These resulted in 50 cases (96 percent) of penetrating vascular injuries and 2 (4 percent) of blunt injury to vessels. Fifty-four percent of patients presented in shock. Active bleeding was recorded in 81 percent, pulse deficit in 65 percent and frank gangrene in 16 per cent. Aneurysms of various types occurred in 14 percent. Associated injuries were fractures in 60 percent, soft tissue injuries in 56 per cent and peripheral nerve injuries in 10 per cent. Overall, 52 arteries and 51 veins were injured, resulting in 15 lacerations, 74 complete transactions and 2 vascular blunt injuries with intimal tears and intraluminal thrombosis. Direct lateral suture of vessels was employed in 13 vessels, anastomosis in 12 vessels, graft interposition in 4 cases, ligation in 49 cases and aneurysmectomy in 3 cases. Three primary amputations were performed versus 7 secondary amputations. Hospital mortality was 16 percent and was mainly due to hypovolaemic shock, acute renal failure and sepsis. PMID- 11768007 TI - Current concepts on pathogenesis of renal tuberculosis. AB - The pathogenesis of renal tuberculosis begins with the initial localization of the tubercle bacilli in the cortical glomeruli causing mechanical stress which lead to alteration in cell morphology, increased rate of protein synthesis and proliferation of resident glomerular cells as well as the infiltrating blood borne cells. The infection may remain localized to the renal parenchyma resulting in various forms of glomerulonephritides and/or gain access to the calyceal system causing pyelocalyceal destruction with subsequent ureteric and urinary bladder involvement. The disease may remain quiesent at the foregoing stage or progress to hydronephrosis and pyonephrosis as a result strictures and obstruction. This communication discusses the immunological responses and various specific lesions resulting from renal injury caused by mycobacterium tuberculosis. PMID- 11768008 TI - Pattern of head and neck cancers among Nigerians in Lagos. AB - Three hundred and eight-one cases of head and neck cancers were studied over a 10 year period (1988 - 1998) at the Lagos University Teaching Hospital, Lagos. The aim was to assess the various sites of primary lesion, gender and age distribution and histopathological types. The International Classification of Diagnosis Oncology's (ICDO) 9TH version was used to categorize sites of primary lesion. A yearly incidence of 38 cases was noted with an overall male preponderance. Forty-five percent of the patients with head and neck cancers were in their forth and fifth decades of life. The nasopharynx was the commonest site of primary lesion (16.8%) followed by the nose, paranasal sinuses and middle ear (ICDO - 160) with 13.6%. Laryngeal cancer ranked third accounting for 12.1% of the cases. Other common sites of primary lesion were: the skin (9.2%), the salivary glands (7.6%), the mandible (7.3%) and the thyroid gland (7.3%). Metastatic cancer in the neck with unknown primary lesion was seen in 2.9% of the patients. Cancers associated with heavy tobacco use e.g. laryngeal cancers, lip and tongue cancers showed a very high male predilection with M:F ratios of 10.5:1, 8:1 and 6:1 respectively. 91% of the head and neck cancers were of epithelial tissue origin while sarcomas accounted for only 6.6% of the cases. The results show that head and neck cancers affect Nigerians especially males at the prime of their working life. The devastating psychosocial effects on the individual, the family and the society are enormous. Emphasis on cancer prevention is recommended. PMID- 11768009 TI - Socio-demographic and clinical profile of patients attending a private psychiatric hospital in Lagos, Nigeria. AB - The pattern of private psychiatric practice in Nigeria was examined by carrying out a prospective study in a private hospital. In all, one hundred and thirty eight (138) consecutive patients of nearly equal sex distribution were seen in a total of about six hundred and forty-four (644) consultation sessions in one year. The young adults (31 - 45 years old) constitute the highest percentage (43.5%) of the patients' age groups. Contrary to the findings of some Nigerian studies in the recent years, neurological disorders mainly epilepsies accounted for the highest number of cases seen (36%). In frequency, this was followed by schizophrenias (22.5%) and affective disorders (18.8%). The peculiarity of these findings could be explained on the ground of referral bias because the hospital is reputed for managing neuropsychiatric disorders; however, despite this factor, the apparent lesson from this study is that psychiatrists in private practice should be equipped with skills to manage neurological disorders. It is concluded that private psychiatric practice in Nigeria is still at an infancy stage but contributing significantly to mental health care services in the country; and the need for further research into private psychiatric practice was highlighted. PMID- 11768010 TI - Lymphoma in adult Nigerians. AB - A review of 143 cases of lymphoma seen in adult Nigerians within a period of 10 years at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. There were 95 males and 48 females patients with an age range of 17 to 88 years. There was male sex predominance both for Hodgkin's and non-Hodgkin's lymphoma. 74% of the cases were non-Hodgkin's lymphoma and 26% were Hodgkin's Nodular lymphomas were very few. Most cases of Hodgkin's disease were of the mixed cellularity subtype. Among non-Hodgkin's lymphomas the intermediate grade predominated, the commonest being diffuse large cell lymphoma. Cases of Burkitts's lymphoma were not common in young adults. Immunohistochemistry plays a vital role in lymphoma diagnosis and sometimes in the differential diagnosis with small blue cell tumours. PMID- 11768011 TI - What does the presence of hypertension portend in the Nigerian with non insulin dependent diabetes mellitus. AB - 132 Nigerians with Non Insulin -dependent diabetes mellitus (NIDDM) were divided into two groups (NIDDM) patients with hypertension and those without) and their clinico-laboratory parameters were studied and analyzed. Their mean age (SD) was 59.5+/-9 years. Body mass index (BMI) was 25.2+/-3.5 kg/m2 and the duration of DM was 6.9+/-6 years. The prevalence of hypertension was 55(41.6%) No significant difference were observed in the age, sex ratio and BMI of both groups but the duration of DM showed a statistical difference between the two groups. However, laboratory parameters such as fasting blood glucose, serum urea, creatinine clearance and degree of proteinuria all showed statistically significant difference between the hypertensive and normotensive groups. Also the hypertensive diabetic group were observed to have more end organ damage i.e peripheral neuropathy, diabetic retinopathy and diabetic nephropathy than the normotensive diabetics. We conclude that, hypertension in NIDDM patients has prognostic implications and so more aggressive efforts be made in detecting and controlling hypertension in DM patients. PMID- 11768012 TI - Bacterial agents of discharging ears and antimicrobial sensitivity patterns in children in Ibadan, Nigeria. AB - Bacteriological studies were carried out on ear swabs from 361 cases of children with discharging ears at the Microbiology Department of the University College Hospital, Ibadan between March 1995 and February 1997. 308 (85.3%) had positive cultures. 78.6% of these yielded one isolate, 19.2% yielded two isolates while 2.2% had three isolates. Pseudomonas spp. Was the predominant agent of CSOM and ASOM. This was followed by Staphylococcus aureus. Other commonly isolated organisms were Proteus and Klebsiella species. Ofloxacin and ciprofloxacin showed the highest activity to all isolates, while two third of the isolates were sensitive to azithromycin, cefuroxime, ceftriazone and gentimicin. PMID- 11768014 TI - Upper gastrointestinal findings and incidence of Helicobacter pylori infection among Nigerian patients with dyspepsia. AB - Gastroscopy is the preferred method of diagnosis of upper gastrointestinal (UGI) disorders which often present with dyspepsia. Since the discovery of helicobacter pylori (H. pylori) as an important aetiological agent in gastroduodenal disease, investigation for this organism during UGI endoscopy has become a standard clinical practice. We have studied a large number of Nigerian patients with dyspeptic symptoms referred for endoscopy for the spectrum of gastroduodenal diseases and the incidence of H. pylori infection. Detection of H. pylori was done on gastric muscosal biopsies either by the Campylobacter-Like Organism (CLO) urease test or by histropathology. A total of 834 patients were studied out of which 268 were investigated for H. pylori. A hundred and ninety-five patients (73%) were positive for H. pylori and the peak age was in the fourth decade. Duodenal ulcer (DU) was the most common endoscopic finding (38.7%). The incidence of H. pylori infection was 76% among patients with DU, gastritis, gastroduodenitis and gastric outlet obstruction. However, all the anterior and pyloric channel Duus tested for H. pylori were positive gastric ulcer (GU) was diagnosed in only 4.7% of patients but 82% of them tested for H. pylori were positive. H. pylori was significantly associated with GU occurring with gastritis. Gastric carcinoma was diagnosed in 52 patients (6.2%) and 50% of those tested for H. pylori were positive. This study shows that H. pylori plays an important role in the aetiopathogenesis of peptic ulcer disease among Nigerian patients and that the diagnosis of anterior and pyloric channel Duus or gastroesophageal polyp disease may be an indicator of massive H. pylori infection. PMID- 11768013 TI - Ketamine anaesthesia for young children undergoing radiotherapy. AB - Young children with radiosensitive malignant tumours often require sedation or anaesthesia to provide immobility for radiotherapy sessions lasting several days. This paper describes the use of repeated intramuscular ketamine anaesthesia for radiotherapy in children age 1.5 to 5 years. Intramuscular ketamine 5-13mg/kg body weight was administered on 280 occasions to 15 children, the highest number of sessions per child being 30 and the least 9. The airway and cardiovascular parameters were well maintained. The time to complete recovery varied from 15 to 90 minutes (mean 52.5+/-31.7 S.D.). Involuntary movements of the tongue, mouth and limbs were observed in 8 patients (52.3%) during 63 sessions (22.5%) but only necessitated interruption of radiotherapy on 6 occasions (2.1%). Ketamine was found to be safe and effective for sedation of young children in the radiotherapy suite and minimal aneasthetic facilities were required. PMID- 11768015 TI - Benign breast disease at Wesley Guild Hospital, Ilesha, Nigeria. AB - A prospective survey of 225 patients carried out over a period of 7years (1992 - 1999) to determine the pattern and outcome of benign breast diseases. Two hundred and seventeen (96.4%) were females and 8 males, with the age ranging from 14-63 years, mean 28.7 SD+10.6 years. The mean age for patients with fibroadenoma was 24 years and 31.6 years for fibrocystic disease of the breast. One hundred and ninety six patients (87.2%) presented with breast lumps or mass, non-menstrual cycle and menstrual cycle related pain in 39(17.3%) and 32(13%) patients respectively and nipple discharge in 60 patients (26.7%). Mean duration of symptoms was 0.91+0.64 years, 2 + 1.2 weeks for inflammatory lesions and 0.86 + 0.56 yers for benign tumours and also menstrual cycle related breast pain. Right side was involved in 162 patients (72%), 85(38%) left side and 77(34.2%) bilateral. Clinical diagnosis was fibrocystic disease 96(42.7%). Fibroadenoma 89 (39.5%), inflammatory conditions 35(15.7%), galactocele in 9(40%) and gynaecomastia in 7(3%) of the patients. Excisional or incisional biopsy was carried out in 197 patients (87.5%), antibiotic and analgestic administration in 35(15.6%) and 29(13%), respectively. Histopathologic analysis showed fibroadenoma in 91 (46.2%), fibrocystic disease 83 (42.2%), and others in 23 (11.6%) cases. The mean follow-up period was 10 months for tumours and I month for others. Postoperative complications were infrequent, there were recurrence either on the ipsilateral or contralateral breast in 10(4.4%) patients of which 3(1.3%) cases were malignant. CONCLUSION: Fibroadenoma was the most common benign breast disease, followed by fibrocystic disease of the breast. Postoperative complications were uncommon. PMID- 11768016 TI - Knowledge and home management of malaria fever by mothers and care givers of under five children. AB - This study documents the knowledge and home management practices of 376 mothers and care givers of under five children on malaria fever. Results revealed that both the knowledge and case management practices were poor as only 179 (46.8%) knew how malaria was transmitted. Of those who knew malaria could be prevented, clearing of bushes and gutters was the commonly stated method (78 or 21.8%), followed by the use of traditional herbs. 'Agbo' by 75(20.9%) mothers. The elders and friends were stated to be the major source of knowledge about malaria by 141(37.5%) mothers. Knowledge scores was significantly higher in older mothers, among the educated, and skilled mothers (P<0.05). As regards practices, self medication with modern drugs was common, these drugs had been given in the home by 265(70.5%) mothers while "Agbo", had been used by 95(25.5%) mothers before presenting at the clinic. Paracetamol was the modern drug often used (217 or 81.8%). Followed by chloroquine (57 or 21.5%). However, drug treatment practice were often incorrect. Chloroquine was prescribed correctly by 15(26.3%) mothers, while 109(50.2%) gave the correct dose of paracetamol. Only 16(4.3%) of the children received anti-malarial on the day the illness began. There is the need for education programmes on malaria for mothers, especially for young, illiterate and unskilled mothers, including the family elders. PMID- 11768017 TI - Rupture of uterine scar with extrusion of twin fetuses into the urinary bladder- a case report. AB - An unusual presentation of a ruptured uterus with extrusion of twin fetuses into the urinary bladder is described. A routine pelvic ultrasound to confirm pelvic collection from a suspended criminally induced abortion revealed a rupture of the anterior wall of the uterus with communication to the urinary bladder and this finding was confirmed at laparatomy. While a high index of suspicion is important in the diagnosis of ruptured uterus, a subtle place for pelvic ultrasound in patients with vaginal bleeding, suprapubic pain and haematuria may be of help. PMID- 11768018 TI - Pattern of bone tumours at the National Orthopaedic Hospital, Lagos, Nigeria. AB - A retrospective study of the pattern of bone tumours over a 6-year period at the National Orthopaedic Hospital, Lagos, Nigeria, has been done. Only those patients with histological diagnosis of bone tumours had their medical records analysed. Thirty-six cases were seen with 19 males and 17 females. The benign cases numbered 24, while malignant cases numbered 12. Osteochondroma and Giant Cell Tumour, numbering 14 and 5 respectively, were the commonest benign lesions, while osteosarcoma numbering 8 cases, was the commonest malignant lesion. The age and sex patterns conform with worldwide patterns. The usual presenting symptoms was mass/swelling with or without pain. The benign cases had excision plus/minus bone grafting of their lesions while some of the malignant cases had ablation before referral to the radiotherapist at the Lagos University Teaching Hospital (LUTH). The treatment outcome could not be verified due to poor follow-up of most cases. PMID- 11768019 TI - Childhood cryptosporidiosis and intestinal parasitosis in association with diarrhoea in Kwara State, Nigeria. AB - The faecal samples of one-hundred and ninety eight children aged 0-14 years with diarrhoea or loose watery stools attending the University of Ilorin Teaching Hospital (U.I.T.H) over a period of 18 months were examined for Cryptosporidium and other intestinal parasites, using a light microscope for direct smear and after concentration for formol-either method and staining with safranin-methylene blue technique. Thirty (15.1%) samples were positive for Crptospo-ridium oocyst while seventy (35.3%) were positive for regular intestinal parasites. The male female ratio for positive cases for the two groups of entric pathogens were 1.3:1 and 3:2 respectively. Concomitant oocyst secretion occurred with other intestinal parasites except for hookworm. Also, the usual intestinal parasites were found more commonly in diarrhoea stools than in control stools where no oocyst was detected. 86.7% oocyst secretion occurred in the 0-2 years age group, but oocysts were not encountered after the age of 4 years. There was a positive correlation between Cryptosporidiosis and other intestinal parasitic agents of diarrhoea (P<0.01). The health implications of these findings are fully discussed. PMID- 11768020 TI - Extensive unusual fibrosarcoma of the right thenar eminence--a case report. AB - A fibrosarcoma of the right thenar eminence is presented. It is interesting that this lesion covered an area larger than the hand before presenting for definite treatment. The tumour was completely excised with minimum functional defect of the affected thumb. Many patients in the African subregion present when their tumours have reached enormous sizes just like this patient. The reason for this late presentation is that the patient prefers to visit herbalists, patent medicine dealers or private hospitals with minimum experience in specialised surgery. The patient's primary reason, apart from superstition, is the high cost of orthodox medical care. Our patients in Nigeria need a lot of health education which will enable them present early and the government should be able to identify their citizens who cannot pay their hospital bills, should be assisted so that operations will be promptly attended to. PMID- 11768021 TI - Pyogenic thyroiditis and HIV infection. AB - Infective thyroiditis remain rare disease entity. Six patients were seen in Jos, Nigeria in the last five years. All of them were HIV positive. The presentation and management of these patients are high-lighted. The clinical features and bacteriology were similar to those previously documented for infective thyroiditis. PMID- 11768022 TI - Spontaneous rupture of incisional hernia--a case report. AB - A case of spontaneous rupture of an incisional hernia is hereby presented. Though very rare in adults, it is a potentially fatal but preventable clinical condition. PMID- 11768023 TI - Pathological fracture complicating epidural local anaesthetic opioid infusion for cancer pain. AB - Two cases of severe bone pains from metastatic cancer, without clinical or radiological evidence of fractures on admission, are presented. Pain control and mobilization were achieved initially with local anaesthetic-opioid epidural infusion. Subsequent loss of analgesia prompted a re-examination, which revealed pathological fractures of the femur. Internal fixation of the fractures resulted in good control such that strong opioids were no longer required. PMID- 11768024 TI - Comment on the article: "Emergency non-obstetrics surgery in pregnancy". PMID- 11768025 TI - Abuse and neglect in the surgically ill child. AB - Child abuse and neglect are a global phenomenon often symptomatic of underlying psychosocial family problems, which may represent a transferred aggression from one or both disturbed parents onto the child. Although the scope has been widely explored in Africa, little has been written on children presenting with surgical lesions. We report 31 children abused by their parents on accounts of frustrations engendered by the children's surgical conditions in Lagos. 26 (83.9%) of these children had major congenital defects while only 5 (16.1%) had acquired lesions. The commonest form of abuse was child abandonment, seen in 9 (29%) of cases. Neglect was recorded in 7 (23%) cases while 2 children were mutilated because of surgical lesions. Three patients were starved, 3 children with colostomy were evicted by landlords while 2 were locked up by parents out of shame. One child died of infanticide. Reasons for abuse included financial constraints, hopelessness and shame associated with grotesque lesions, broken homes and maternal pregnancy. Doctors and nurses engaged in the care of gross congenital anomalies and other major surgical lesions should anticipate this problem and evolve appropriate strategies to deal with it. The social worker should be involved early enough in the management. Provision of adequate social safety nets, affordable medical care and specific legal protection for children will curtail this ugly trend in our society. PMID- 11768026 TI - Pulmonary tuberculosis in Kumasi, Ghana: presentation, drug resistance, molecular epidemiology and outcome of treatment. AB - To assist implementation of tuberculosis (TB) control measures, knowledge of the disease characteristics in a community is essential. This study in Kumasi, Ghana, correlates the clinical presentation, microbiology, molecular epidemiology and clinical outcome of thirty consecutively diagnosed patients with new smear positive pulmonary TB. Several important factors that potentially promote disease transmission in the community were identified: patients had prolonged duration of productive cough prior to diagnosis (mean=4.1 months; SD=2.1); the disease was typically advanced at presentation and Ziehl-Neelson sputum smears indicated a high bacterial load (80% graded > AFB++); home accommodation was overcrowded with a mean of 3.3 other persons sleeping in the same room as the patients at night. IS6110 restriction fragment length polymorphism (RFLP) fingerprinting of 25 isolated (23 Mycobacterium tuberculosis and 2 Mycobacterium africanum) from epidemiologically unrelated cases identified 3 identical strains and 3 clusters containing 2, 4 and 8 isolates of > or =80% similarity, suggesting high rates of disease transmission. A high prevalence of primary resistance to isoniazid was found (6 out 26; 23%) but resistance to rifampicin, pyrazinamide, ethambutol, streptomycin and ciprofloxacin was not detected. Smear coversion at 2 months and final outcome of treatment with short courses chemotherapy were independent of isoniazid resistance, but the rate of treatment default was unacceptably high (37%). High rates of disease transmission, primary isoniazid resistance and treatment default all indicate poor TB control. The use of rifampicin-containing short-course chemotherapy in this community must be accompanied by adequate resources and infrastructure to ensure very stringent treatment supervision to improve case-holding and reduce the risk of multi-drug resistance. PMID- 11768027 TI - Complications of sinusitis in Ibadan, Nigeria. AB - Nowadays the complications arising from sinusitis are rare since the introduction of antibiotics. However sinusitis and its complications are still life threatening and if neglected may result in high morbidity and mortality. It is the purpose of this study to draw attention to the effects of the spread of infection beyond the sinus wall and thus to influence the clinician in his management in order to prevent the subsequent spread of the disease, and secondly make him aware of the sinogenic origin of these complications when he sees them. A retrospective study of 90 patients with sinusitis seen over a ten year period between 1988 and 1997 in the ENT Department, University College Hospital, Madan was (lone and those that had complications were further analysed to meet the objectives of this study. There were 90 patients seen with sinusitis over the ten years period, out of which 33 (37%) cases had complications, 17 males and 16 females (M.F.1:1). The average age of cases with complications was 28 years (age range 2.5 - 75 years). 66.6% of the complications cases occurred in age group under 30 years of age. Thus children and young adults were mostly affected. Twenty-six cases (79%) of chronic sinusitis developed complications while in acute sinusitis there were 7 cases (21%). The site affected most commonly by complications was the orbit (41%) followed by Sinus wall (32%), orophyarynx (18%), intracranial (5%); no car complications were seen. The type of complications seen at various sites and their incidence were also highlighted. Thus with this study it is hoped that clinicians would be reminded that complications of sinusitis still occur and hence be aware of the necessity to recognize and prevent them as rapidly as possible to avoid serious consequences. PMID- 11768028 TI - The efficacy and safety of once-daily Kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy. AB - This multicenter, randomized, double-blind study compared the efficacy and safety of once-daily oral granisetron 2 mg (n = 134) and placebo (n = 126) as prophylaxis for nausea and emesis in patients receiving upper abdominal fractionated radiotherapy. Patients were scheduled to receive 10-30 fractions of radiotherapy; granisetron (two 1-mg tablets) or placebo was administered 1 hr before radiotherapy on each scheduled treatment day. Treatment comparisons were made at 24 hr and at 10 and 20 fractions. Patients treated with granisetron experienced greater emetic control than those treated with placebo as evidenced by median times to first emesis (35 vs. 9 days, p < 0.001) and first nausea (11 vs. 1 day, p < 0.001). Overall endpoint analysis showed that proportionally more granisetron than placebo patients were emesis free (57.5% vs. 42.1%, p = 0.0047) and nausea free (30.6% vs. 16.7%, p = 0.0042). Furthermore, 25% more granisetron treated than placebo-treated patients were emesis free and 20% more were nausea free on at least 80% of study treatment days. The most commonly reported adverse experiences in granisetron-treated patients were diarrhea, asthenia, and constipation. These findings demonstrate that a once-daily, 2-mg dose of oral granisetron is well tolerated and significantly more effective than placebo in preventing nausea and emesis induced by fractionated radiotherapy to the upper abdomen. PMID- 11768029 TI - Serum and tissue c-erb B2, bcl-2, and mutant p53 oncoprotein levels in nasopharyngeal cancer. AB - To date there are no prognostic factors that can account for the biology and disease behavior in nasopharyngeal cancer. Therefore, identification of new factors that can help in predicting the behavior of the disease and characterizing the subgroup with more aggressive tumors more likely to benefitfrom chemotherapy is important. In this study, c-erb B2, bcl-2, and mutant p53 protein levels were investigated in sera and tumor tissue of patients with nasopharyngeal cancer. Serum c-erb B2 levels were significantly higher in the patients than in the healthy subjects. No meaningful difference was observed between the serum and tissue levels of the mutant p53 protein. Tissue bcl-2 concentrations were considerably high. Our results suggest that serum c-erb B2 levels may aid in identifying a subgroup of patients with a poorer response rate to first-line treatment. PMID- 11768030 TI - Endothelin converting enzyme-1 expression in endometrial adenocarcinomas. AB - Endothelin-1 (ET-1) is a potent mitogen in various precursor tumor cells, including endometrial adenocarcinoma. It is proposed that ET-1 produced by endometrial adenocarcinoma may participate in the angiogenesis of this carcinoma in vivo. Endothelin converting enzyme-1 (ECE-1) is the key enzyme that synthesizes ET-1. In this study, we tried to demonstrate the expression of ECE-1 in endometrial carcinomas. Deparaffinized tissue sections from patients with endometrial adenocarcinoma were analyzed by immunohistochemistry for the presence of ECE-1. Our study showed that the expression of ECE-1 was markedly increased in 9 of 15 (60%) well-differentiated endometrial adenocarcinomas; in contrast, only 2 out of 10 (20%) control specimens showed a mild labeling. With new selective inhibitory molecules emerging, research is currently evaluating the possible inhibition of ECE-1 as an alternative approach for the treatment of endometrial as well as other carcinomas. PMID- 11768032 TI - Effect of hyperthermia on AKR lymphoma variants differing in degree of malignancy. AB - The effect of hyperthermic treatment on AKR lymphoma cells of varying malignancy was investigated. Tumor cells were pretreated at 37 or 43 degrees C and then injected to mice. The effect on the highly malignant variant, TAU-38, was compared to that on the low-malignancy variant, TAU-39, following both subcutaneous (s.c.) and intravenous (i.v.) inoculation. Hyperthermia showed no effect on the TAU-39 variant following s.c. inoculation on the primary tumors or mice survival, but the TAU-38 variant exhibited a significant delay of tumor appearance following treatment, namely, decreased tumor size and increased life span. Following i.v. inoculation, in both variants, hyperthermia caused a significant decrease in metastatic spread and an increased life span. We conclude that hyperthermia, in addition to exerting a greater effect on the high malignancy variant, acts at the late phases of metastasis. Hyperthermia might therefore have a place in the management of cancer in its advanced disseminated phase. PMID- 11768031 TI - Effect of phosphatidic acid on human breast cancer cells exposed to doxorubicin. AB - We previously demonstrated that phosphatidic acid (PA) induces chemotactic migration of highly metastatic breast cancer cells MDA-MB-231. The widely used anticancer drug doxorubicin was reported to induce apoptosis of cancer cells. Growth factors such as epidermal growth factor (EGF) and bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SPP) have been shown to enhance viability and to protect cancer cells against apoptosis. In this study, we investigated the effect of PA on MDA-MB-231 cells exposed to the anticancer drug doxorubicin. Cell migration toward PA was partially inhibited by doxorubicin treatment, and PA moderately diminished cell cycle arrest of cells exposed to doxorubicin. Although PA itself was not able to induce apoptosis of MDA-MB-231 cells, apoptosis of cells exposed to doxorubicin was markedly enhanced by PA treatment. Thus, PA is able to increase the apoptotic potential of doxorubicin, and may regulate the effects of doxorubicin used for chemotherapy. PMID- 11768033 TI - Expression of bisecting N-acetylglucosaminyltransferase-III in human hepatocarcinoma tissues, fetal liver tissues, and hepatoma cell lines of Hep3B and HepG2. AB - In this paper, uridine diphosphate (UDP)-N-acetylglucosamine/beta-D-mannoside beta-1,4 N-acetylglucosaminyltransferase III (GlcNAc-transferase-III C 2.4.1.144) activity was determined in human hepatoma cell lines of Hep3B and HepG2, and also compared with those of normal liver tissues and primary hepatocytes. GlcNAc transferase-III enzymes of Hep3B and HepG2 were mainly detected in the membrane fraction. When GlcN,GlcN-biant-PA and UDP-GlcNAc were used as substrates, the Km values (4.7 mM for UDP-GlcNAc and 1.1 mM for GlcN, GlcN-biant-PA) of Hep3B GlcNAc transferase-III were distinguishable from those of HepG2 GlcNAc-transferase-III (6.8 mM for UDP-GlcNAc and 3.4 mM for GlcN,GlcN-biant-PA). Furthermore, Hep3B enzyme in membrane fraction showed about 1.5-fold higher specific activity (1423 pmol/hr/mg) than that of HepG2 (1066 pmol/hr/mg). Normal liver cells and primary adult hepatocytes are characterized by a very low level of GlcNAc-transferase-III activity, whereas human hepatoma cells exhibited high activities. These data were supported by reverse transcription-polymerase chain reaction results, showing that expression of the GlcNAc-transferase-III mRNA increased in proportion to the enzymatic activities. Although the mechanism underlying the induction of this enzyme is unknown, lectin blot analysis showed that oligosaccharides in many glycoproteins were observed in hepatoma cells. By treating hepatocarcinoma cultures that express GlcNAc-transferase-III with inhibitors (tunicamycin, deoxymannojirimycin, and swainsonine) of different steps of the glycosylation, we provide evidence that expression of GlcNAc-transferase-III mRNA is dependent on glycosylation of cellular proteins. PMID- 11768034 TI - Palliative chemotherapy in pretreated patients with advanced cancer: oral trofosfamide is effective in ovarian carcinoma. AB - Thirty-four patients with advanced cancer of various origins and documented disease progression were treated with continuous daily doses of 50-150 mg of oral trofosfamide (TRO). Of 31 evaluable patients, 5 responded to this treatment (1 complete remission and 4 partial remissions) and 12 patients had stable disease. Four of 9 patients with advanced ovarian cancer resistant to platinum-containing regimens and paclitaxel responded to oral TRO. The median treatment duration was 26 weeks for responders and 6 weeks for nonresponders, with cumulative doses of up to 46.000 mg TRO. Response duration was 11-47 weeks. No significant side effects were observed. Oral TRO given in the outpatient setting seems to be an attractive therapeutic option for heavily pretreated cancer patients, and it has remarkable antitumor effects in patients with ovarian cancer. PMID- 11768035 TI - Cognitive effects of standard-dose chemotherapy in patients with cancer. AB - Adult cancer survivors have reported experiencing persistent changes in cognitive function following treatment with chemotherapy. Increasing evidence supports the hypothesis that standard-dose chemotherapy can produce cognitive deficits in a subgroup of adult cancer survivors. Although these cognitive changes tend to be subtle deficits in memory, concentration, and the ability to remain focused or organized, these alterations in cognitive ability can have a significant impact on patients' quality of life generally, and on meeting career and educational goals specifically. This manuscript reviews the literature relevant to the cognitive impact of standard-dose chemotherapy in adults, outlines methodological issues related to the study of cognitive functioning in people with cancer, and discusses future directions for research in this area. PMID- 11768036 TI - Silicone breast implants and cancer. PMID- 11768037 TI - Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments. AB - Antibodies have long been considered to be potential anticancer agents because of their specificity for cell-membrane antigens. Applications of hybridoma and recombinant DNA technology have led to the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies for clinical use. Whole antibodies may produce anticancer effects in conjunction with the immune system by interaction with complement proteins and/or effector cells via the Fc portion of the antibody molecule. Antibodies may also neutralize circulating ligands or block cell membrane receptors and thus interrupt ligand/receptor interactions and signal transduction that are associated with proliferative or anti-apoptotic effects. The anti-idiotype network cascade provides a rationale for antibodies as vaccine therapy. Antibodies may also serve as the guiding or targeting system for other cytotoxic pharmaceutical products such as (i) radiolabeled antibodies for radioimmunodetection and radioimmunotherapy; (ii) immunotoxins; (iii) chemotherapy/antibody conjugates; (iv) cytokine/antibody conjugates; and (v) immune cell/antibody conjugates. After years of anticipation, as of late 1999 there were four monoclonal antibodies that had been approved by the U.S. Food and Drug Administration based on activity against human malignancy, all of which are in widespread clinical use. Several other products are in various stages of clinical trial testing. Monoclonal antibodies have joined interferon-alpha, interleukin-2 (IL-2), and various hematopoietic growth factors as well-established components of biological therapy, the fourth modality of cancer treatment. PMID- 11768038 TI - Environmental and host factors in testicular germ cell tumors. PMID- 11768039 TI - Oral fluoropyrimidines: are they the equivalent of parenteral infusional 5 fluorouracil? PMID- 11768040 TI - Passive smoking in infants, children and adolescents. The effects of diet and socioeconomic factors. AB - OBJECTIVES: Many studies have associated environmental tobacco smoke (ETS) exposure with an increased risk for various diseases in infants and children, and although superficially the evidence is compelling, on closer scrutiny socioeconomic factors, especially diet, could have a greater contributory effect. An analysis of this evidence was made. RESULTS: Studies which have correlated smoking during pregnancy with low birth weight have considered weight gain and cholesterol levels as a measure of nutrition in the mother, but not the micronutrient content of the diet to which low birth weights could be due. Several authors have attributed ETS exposure to the presence of abnormal lipid profiles in children and adolescents, without considering the diet of the latter, and the abnormal lipids have been linked to a subsequent increased risk for atherosclerosis. The evidence linking lower respiratory infections and bronchitis with passive smoking is strong, although it seems likely that the diet of the mother during pregnancy or breast feeding is equally important. Similarly, increased risks for asthma, otitis media and sudden infant death syndrome have been attributed to the effects of passive smoking, without adequate allowance for confounding by other socioeconomic factors. CONCLUSION: After consideration of the accumulated evidence, it seems improbable that the small exposure could produce all of the effects claimed. PMID- 11768041 TI - Evaluation of occupational and leisure time exposure assessment in a population based case control study on leukaemia. AB - OBJECTIVES: To increase the credibility of retrospective exposure assessments. documentation of the procedures and presentation of measures on quality control is recommended. The aim of this study was to present and evaluate the procedures used in a case-control study on leukaemia. METHODS: A series of 1,087 cases and matched controls were interviewed. Exposure assessments were performed for 13 occupational agents and ten leisure-time activities and the confidence of the assessments was coded. The exposure assessments were performed blind by three occupational hygienists. Ten percent of the interviews were reassessed by two of the three occupational hygienists. RESULTS: The leisure-time activities contributed to a large extent to the overall prevalence of exposure. For organic solvents approximately 25% of the controls classified as exposed would be misclassified if leisure-time exposure were not considered. The proportions of subject assessments with low confidence were higher for next-of-kin than for in person interviews. A negative correlation was seen between the proportions of assessments with low confidence and the reliability. A significant difference was seen in the inter-rater comparison between cases and controls when the reliability was calculated for each assessed period; no difference was seen for the subject assessments used for relative risk estimation. CONCLUSION: When low dose exposure in epidemiological studies are being assessed there is an obvious risk of misclassification if leisure-time activities are not included. Furthermore, the reliability of the assessments may suffer if next-of-kin interviews are used to a large extent. For cancers with poor prognoses, prospective studies are preferable to minimise possible information bias. PMID- 11768042 TI - Biomonitoring of exposure to nitrous oxide, sevoflurane, isoflurane and halothane by automated GC/MS headspace urinalysis. AB - OBJECTIVES: The goal of the present study was to develop an automated method to assess by biological monitoring, the volatile-anaesthetic exposure (nitrous oxide, sevoflurane, isoflurane and halothane) in operating theatre personnel. METHODS: Post-shift urine samples were analysed by gas chromatography-mass spectrometry coupled with static headspace sampling (GC-MS/ HSS); intra-assay % RSD (n= 10) was less than 5% for nitrous oxide and less than 7% for each halogenated vapour. The biomonitoring method was validated with air monitoring data, obtained by personal samplers and a similar GC-MS method. The sensitivity achieved by single ion monitoring (SIM) was sufficient to reveal low biological and environmental exposure averages down to 1 microg/l(urine) and 0.5 ppm for nitrous oxide and 0.1 microg/l(urine) and 50 ppb for halogenated compounds, respectively. RESULTS: In 1998 we collected and analysed 714 post-shift urine samples for the biological monitoring of volatile anaesthetics in the urine of the operating-theatre personnel of Sant'Orsola-Malpighi Hospital (Bologna, Italy). Our data showed that nitrous oxide (N20), the anaesthetic most largely used in general anaesthesia, is still the decisive factor in operating-theatre pollution. Moreover, on the basis of our results, working in close contact with anaesthetics seems to be the main determinant of risk: surgical nurses and anaesthesiologists are the most-exposed professional categories (mean post-shift urinary N2O approximately 65 microg/l(urine)) while general theatre staff, surgeons, and auxiliary personnel have significantly lower exposure. CONCLUSIONS: The biological monitoring of post-shift unmodified urinary volatile anaesthetics was confirmed to be a useful tool for evaluating individual exposure to these chemicals. The urinary concentrations of N2O and of halogenated vapours might reflect, to a certain extent, the external exposure to these compounds, and respiratory air-monitoring data support the validity of biological monitoring. Furthermore, the good relationship between air and urinary concentration of anaesthetics in people working in closer contact with these chemicals may be a good indirect means of revealing the bad air conditions of operating rooms, and may contribute to the highlighting and correction of service defects in anaesthesiology equipment and of human errors. PMID- 11768043 TI - Musculoskeletal complaints, functional capacity, personality and psychosocial factors. AB - OBJECTIVES: The aim of the research was to study the association between psychosocial and personality factors, and neck and wrist-hand musculoskeletal complaints, taking account of the occupational factors of force, posture and repetitiveness, and non-occupational risk factors such as sport, hobbies, medical history. METHODS: During personal interviews 133 women from seven different companies, working at constraining workplaces (very repetitive work), answered several questionnaires. These concerned: personal characteristics and history; work characteristics; psychosocial factors (perception and appreciation of the work situation, satisfaction at work, stress symptoms, Karasek questionnaire) and personality factors (neuroticism, conscientiousness, type-A behavior). They also undertook functional and psychomotor tests (wrist angles, grip strength and a dexterity test). Logistic regression models were calculated. RESULTS: Wrist-hand complaints appear to be associated with some personal characteristics (smoking habits, fewer hobbies), work constraints (fewer breaks, heavy lifting efforts) and some personality (introversion) and psychosocial factors (worse appreciation of work). Neck complaints are also associated with some personal characteristics (young people, small, bad health, hormonal problems, fewer hobbies), some personality (urgency of time) and psychosocial factors (constraints as seen by the supervisor). CONCLUSION: The study confirms the multifactorial character of the musculoskeletal disorders and underlines the need for a global ergonomic approach to work situations, taking into account all their physical, psychological and social components. PMID- 11768044 TI - Cancer incidence and work place exposure among Swedish biomedical research personnel. AB - OBJECTIVE: This cohort study aimed to elucidate cancer occurrence in relation to occupational exposure to specific chemical, biological and physical agents among biomedical research laboratory personnel in Sweden. METHODS: Standardized incidence ratios (SIRs) for the period 1970-1994 were calculated for specific exposures in the laboratory group (n = 3,277) and for personnel working in non laboratory departments (n = 2,011), as an internal reference group. Expected numbers were based on national cancer rates. RESULTS: The total number of cancer cases was lower than expected in both laboratory and non-laboratory personnel. Elevated SIRs were noted for malignant melanoma among female laboratory employees for whom use was reported of solvents (SIR 2.73; CI 1.10-5.63) and of selected carcinogenic (International Agency for Research on Cancer (IARC) group 2B) agents (SIR 3.15; CI 1.16-6.85). A light increase of the risk estimate for breast cancer was also observed. CONCLUSIONS: In general, there were few cases of cancer in this comparatively young cohort, but the findings give some indication of increased risks for malignant melanoma in female laboratory personnel after exposure to organic solvents or substances classified by IARC as being possibly carcinogenic. PMID- 11768045 TI - Mortality during winter smog episodes 1982, 1985, 1987 and 1993 in the Czech Republic. AB - OBJECTIVES: Severe air pollution episodes were recorded during the 1980s and early 1990s in the Czech Republic as a result of widespread combustion of brown coal. A population-based retrospective study investigated the relationship between air pollution and daily mortality in six highly polluted areas of the Czech Republic during smog episodes in 1982, 1985, 1987, and 1993. METHODS: Total daily mortality, mortality by gender and age, cardiovascular mortality, respiratory mortality, data on weekly incidence of acute respiratory diseases and daily mean concentrations of sulphur dioxide and suspended particulate matter were used in the model. The effects of smog on daily mortality were estimated by multiple linear regression analysis. RESULTS: Significant increases in mortality were observed for the 1982 and 1987 episodes (6% and 9%). In 1982, mortality was significantly associated with mean concentration of sulphur dioxide (SO2) of the current and the preceding days and with the 4-day moving average. In the 1985 episode a significant increase in respiratory mortality in men and in both genders together, lagging by 2 and 3 days, was detected. During the 1987 episode significant associations of total daily mortality, mortality in persons over 65 years of age and mortality from cardiovascular or respiratory diseases with 4-day moving average of both pollutants were found. For the 1993 episode a significant association between mortality in women under 65, lagging by 3 days, and mean concentration of suspended particulate matter (SPM) was observed. CONCLUSIONS: Most of the results are consistent with other studies aimed at episodic air pollution during the 1950s and 1960s in Western Europe and the USA, in which outdoor air pollution was shown to be a significant predictor of mortality. However, non-significant or opposite associations between air pollution and mortality indicate that other factors may also play an important role. A stronger effect on men under 65 years of age, suggested by a previous Czech study was not confirmed. PMID- 11768046 TI - Outdoor sulphur dioxide and respiratory symptoms in Czech and Polish school children: a small-area study (SAVIAH). Small-Area Variation in Air Pollution and Health. AB - OBJECTIVES: Air pollution has been linked to respiratory outcomes but controversy persists about its long-term effects. We used a novel technique to estimate the outdoor concentrations of sulphur dioxide (SO2) at small-area level to study the long-term effects on respiratory symptoms and disease in children. METHODS: As part of the international SAVIAH study, parents of 8,013 children aged 7-10 studied in Prague (Czech Republic) and Poznan (Poland) completed a questionnaire covering respiratory health, demographic and socio-economic factors and health behaviours (response rate 91%). This report is based on 6,959 children with complete data. Outdoor SO2 was measured by passive samplers at 80 sites in Poznan and 50 sites in Prague during 2-week campaigns. Concentrations of SO2 at each point (location) in the study areas were estimated from these data by modelling in a geographical information system. The mean of the estimated SO2 concentrations at children's homes and schools was used as an indicator of exposure to outdoor SO2. RESULTS: The prevalence of respiratory outcomes was similar in both cities. In the pooled data, 12% of children had experienced wheezing/whistling in the past 12 months; 28% had a lifetime prevalence of wheezing/whistling; 14% had a dry cough at night; and 3% had had asthma diagnosed by a doctor. The estimated mean exposure to outdoor SO2 was 80 (range 44-140) microg/m3 in Poznan and 84 (66-97) microg/m3 in Prague. After socio-economic characteristics and other covariates were controlled for, SO2 was associated with wheezing/whistling in the past 12 months (adjusted OR per 50 microg/m3 1.32, 95% CI 1.10-1.57), lifetime prevalence of wheezing/whistling (OR 1.13, 95% CI 0.99 1.30), and lifetime prevalence of asthma diagnosed by a doctor (OR 1.39, 95% CI 1.01-1.92). The association with dry cough at night did not reach statistical significance. CONCLUSIONS: In these two Central European cities with relatively high levels of air pollution, small-area based indicators of long-term outdoor winter concentrations of SO2 were associated with wheezing/whistling and with asthma diagnosed by a doctor. PMID- 11768047 TI - Scleroderma and occupational exposure to hand-transmitted vibration. AB - OBJECTIVES: To determine whether occupational exposure to hand-transmitted vibration is a risk factor for scleroderma (systemic sclerosis, SSc), two case control studies were conducted in the provinces of Trento and Verona, northeastern Italy. METHODS: In the Trento study, 21 patients with a diagnosis of either systemic or localised scleroderma were recruited from those admitted to all hospitals of the province from 1 January 1976 to 31 December 1991. For each case, two age- and gender-matched controls were selected. In the Verona study, cases included 55 patients diagnosed with SSc and clinically followed at the rheumatology clinic of the local university hospital between 1 January 1997 and 30 June 1999. The controls included 171 subjects frequency-matched by gender and age group. In both studies, all subjects were interviewed by structured questionnaire containing items on personal characteristics, smoking and drinking habits, use of medicines, occupational history and complete medical history. Women were also investigated about silicone implants and cosmetic surgery. Jobs and job tasks involving the use of vibratory tools, with or without concomitant exposure to silica dust in mining and non-mining occupations, were carefully investigated. A minimum criterion of 6 months was required for exposure duration. RESULTS: In the Trento study, men with scleroderma were more likely than controls to have had exposure to hand-transmitted vibration (odds ratio (OR) 1.5, 95% confidence interval (95% CI) 0.1-74.1) or silica dust (OR 5.2, 95% Cl 0.5-74.1), but the association was not significant. The scleroderma patients were miners or stone workers who had operated jackhammers and rock drills. In the Verona study, a greater, although not statistically significant, odds of SSc was observed in men exposed to hand-transmitted vibration (OR 2.4, 95% CI 0.4-14.0) and in women exposed to silica (OR 2.4, 95% Cl 0.4-15.5). The SSc patients with vibration exposure were machinery operators or metal workers who had used grinders and impact wrenches. CONCLUSIONS: Our case-control studies did not show a significant association between scleroderma and hand-transmitted vibration, with or without concomitant exposure to silica dust. Owing to the rarity of the disease and the small number of cases in the present studies, a genetic susceptibility to connective tissue disorders in SSc patients with occupational exposure to hand transmitted vibration and/or silica cannot be ruled out. PMID- 11768048 TI - Physical load and psychological demand at work during pregnancy and preterm birth. AB - OBJECTIVES: To evaluate the effect of physical workload and psychological demand on all preterm births, and to determine whether these risk factors have the same effect on different types of preterm birth (moderate versus very preterm birth) and different modes of delivery onset (spontaneous versus indicated preterm birth). METHODS: A case-control study was carried out in two public general hospitals in the Valencia Region, Spain. All preterm births (228) which occurred between 22 and 36 completed weeks of amenorrhea and 348 controls of 37 or more completed weeks of amenorrhea were included. The information was collected by interviewing women within 2 days of their giving birth. Physical workload, psychological demand, weekly working hours and daily time spent commuting between home and work were used as explanatory variables. A polytomous logistic regression was carried out. RESULTS: Exposure to medium or high level physical workload increases the risk of preterm birth, with an adjusted odds ratio (OR) of 1.59 and 2.31, respectively. The risk of moderate preterm birth was greater in women with a medium or high level of physical workload, OR: 1.73 and 2.35, respectively. The same trend was observed for very preterm birth. Physical workload showed a different effect on spontaneous and indicated preterm birth. The exposure to medium and high level physical workload increases the risk of indicated preterm birth, with an OR of 2.74 and 3.88, respectively. The same trend was seen in the case of spontaneous preterm birth. Psychological demands were not associated with preterm birth. CONCLUSIONS: High physical exertion increases the risk of preterm birth in Spain. The magnitude of the effect of physical workload on moderate and very preterm birth is similar, but is higher on indicated preterm birth than on spontaneous preterm birth. Psychological demands show no effect on the risk of preterm birth. PMID- 11768049 TI - Task profile and risk of occupational hepatitis A infection in sewerage workers. AB - OBJECTIVE: The aim of the study was to assess to what extent parameters of task related occupational exposure influence anti-hepatitis A virus (anti-HAV) seroprevalence in sewerage workers, using a new instrument for classification of exposure. METHODS: A new instrument for the assessment of work-related infection hazards was developed based on expert interviews, evaluation of literature and theoretical considerations. It was included in a questionnaire for collecting detailed information on occupational exposure, safety awareness, safety behaviour and socio-demography. Anti-HAV status was assessed for all (n = 343) (non vaccinated) study participants. RESULTS: Marked differences in task profile and task-related exposure within the group of sewerage workers were found, underlining the necessity of a detailed exposure analysis. In a multivariate model three risk factors that were related significantly to anti-HAV positivity were identified: age, country of origin and task-related exposure. CONCLUSIONS: Since task profiles and occupational exposure differ strongly within the job category of sewerage workers. evaluation of endangerment has to reflect individual task-related exposure. The task-exposure matrix developed and presented in this study is a practicable and valid instrument for exposure assessment and may be used for the exposure analysis of further biological agents in this working environment. Besides the known risk parameters age and origin, our study demonstrates a dose-response relationship between the degree of occupational exposure and the anti-HAV seroprevalence. Therefore, an effective worksite HAV-prevention programme should consider all technical, structural and educational measures that help to reduce individual exposure. PMID- 11768050 TI - Cultural influences on cognitive representations of conflict: interpretations of conflict episodes in the United States and Japan. AB - This article integrates theory from the cognitive tradition in negotiation with theory on culture and examines cultural influences on cognitive representations of conflict. The authors predicted that although there may be universal (etic) dimensions of conflict construals, there also may be culture-specific (emic) representations of conflict in the United States and Japan. Results of multidimensional scaling analyses of U.S. and Japanese conflict episodes supported this view. Japanese and Americans construed conflicts through a compromise versus win frame (R. L. Pinkley, 1990), providing evidence of a universal dimension of conflict construal. As the authors predicted, Japanese perceived conflicts to be more compromise-focused, as compared with Americans. There were also unique dimensions of construal among Americans and Japanese (infringements to self and giri violations, respectively), suggesting that identical conflict episodes are perceived differently across cultures. PMID- 11768051 TI - Interaction of social skill and general mental ability on job performance and salary. AB - Job and organizational changes have promoted the importance of social skill at work, yet research in this area has been limited. The authors investigated the interaction between social skill and general mental ability (GMA) in the explanation of job performance and salary, controlling for personality and demographic characteristics. The results indicated that the relationships between social skill and job performance were stronger among workers high than low in GMA. In a similar manner. the relationships between GMA and job performance were stronger among workers high than low in social skill. The interaction on salary indicated that increases in social skill (or GMA) for high-GMA (or social skill) individuals were associated with higher salary levels. It is interesting, however, that increases in social skill (or GMA) for those low in GMA (or social skill) contributed to lower salaries. Implications of these results and directions for future research are discussed. PMID- 11768052 TI - Goal congruence in project teams: does the fit between members' personal mastery and performance goals matter? AB - Research on team goals rarely considers the impact of congruence in perceptions of personal goals of self versus other members. In this study of 324 members of 64 short-term project teams, polynomial regression analysis was used to explore how congruence in personal and perceived team mastery and performance goals affected individual outcomes. Results indicated that congruence in perceived performance goals elicited greater individual satisfaction and contributions, regardless of goal strength (i.e.. high or low personal performance goals). Conversely, perceived team mastery goals had a greater effect on individual outcomes than did perceived congruence in self-other mastery goals. Congruent self-actual team goals showed weaker but similar relationships to individual outcomes, but contrary to hypotheses, this effect was not mediated by congruence in perceived self-other goals. PMID- 11768053 TI - A closer look at the relationship between justice perceptions and union participation. AB - In this study, a series of nested models was tested to assess the extent to which the relationship between process-related justice and union participation is mediated by perceived union support and union commitment. Members of a steelworkers' local (N = 615) participated in the study. Fit indices most strongly supported a fully mediated model. Unlike previous research, process related justice was operationalized as 2 distinct variables: procedural and interactional justice. Interactional justice was found to have a substantially stronger relationship with support perceptions than procedural justice. Results also indicated union support accounted for a greater amount of unique variance in union commitment than perceived union instrumentality. The results are discussed in relation to trust theory and the generalization of organization science across different types of organizations. PMID- 11768054 TI - Influence of performance evaluation rating segmentation on motivation and fairness perceptions. AB - This study investigated the impact of rating segmentation (i.e., the number of alternative appraisal categories available for rating employee performance) on motivation and perceptions of fairness. Participants were 305 student volunteers who performed a catalog search task. A 2 x 4 factorial design with 2 performance rating systems-low segmentation (3 categories) and moderate segmentation (5 categories)--and 4 performance levels was used. Overall, the results indicated that the 5-category system resulted in higher self-efficacy regarding participants' ability to reach the next higher rating category. higher goals for rating improvement, and higher rating improvements than the 3-category system. The effects of rating system and performance rating on rating improvement were partially mediated by self-efficacy and personal goals. The rating system and the performance rating affected perceptions of distributive and procedural justice. PMID- 11768055 TI - Prejudice matters: understanding the reactions of Whites to affirmative action programs targeted to benefit Blacks. AB - The authors examined, in 2 studies, the effects of equal employment opportunity/affirmative action (EEO/AA) policies on Whites' job-related attitudes. First, in an experiment, White prospective job recruits, as expected, rated a potential employer whose EEO/AA policies were framed as targeted to benefit Blacks as less attractive than a potential employer whose EEO/AA policies were framed more generally. Second. the results of a field study showed that prejudice against Blacks moderated the relationship between Whites' perceptions that their organization's EEO/AA policies were targeted to benefit Blacks and their satisfaction with promotion opportunities. Specifically, among prejudiced Whites, this relationship was negative and considerable in size (r = -.39. p < .01); whereas, among nonprejudiced Whites, it was negligible (r = -.04, ns). The implications of our findings for the study of prejudice in organizations are discussed. PMID- 11768056 TI - Impact of guided exploration and enactive exploration on self-regulatory mechanisms and information acquisition through electronic search. AB - Following instruction in basic skills for electronic search, participants who practiced in a guided exploration mode developed stronger self-efficacy and greater satisfaction than those who practiced in a self-guided exploratory mode. Intrinsic motivation was not affected by exploration mode. On 2 post-training tasks, guided exploration participants produced more effective search strategies. expended less effort, made fewer errors, rejected fewer lines of search, and achieved higher performance. Relative lack of support for self-regulatory factors as mediators of exploration mode impacts was attributed to the uninformative feedback from electronic search, which causes most people to remain at a novice level and to require external guidance for development of self-efficacy and skills. Self-guided learning will be more effective on structured tasks with more informative feedback and for individuals with greater expertise on dynamic tasks. PMID- 11768057 TI - Dispositions and work reactions: a multilevel approach. AB - Multiple levels of analysis were used to examine the link between stable dispositions and more state-oriented work reactions such as job satisfaction. Participants in the study were employees from a large state education system and an urban hospital. The proportion of between-group variance in positive work affect, negative work affect, and job satisfaction increased after dispositional measures of neuroticism and extraversion were included, although the confidence intervals overlapped. Aggregate perceptions of excessive job demands explained more between-group variance in work reactions after dispositions were included. Previous research conducted at a single level of analysis suggests that the inclusion of stable dispositions can attenuate the link between work characteristics and work reactions. The present study suggests the opposite pattern when group-level variance is considered. PMID- 11768058 TI - Coping with sexual harassment: personal, environmental, and cognitive determinants. AB - A multidimensional coping typology and a process model of coping were used to examine coping strategies in response to sexual harassment, the personal and environmental determinants of these strategies, and the cognitive processes underlying strategy choice. Survey responses of 15,404 military members who reported unwanted sex-related attention were analyzed. Strong support was found for the usefulness of both the typology and the model. Choice of specific coping strategies used in response to sexual harassment varied significantly depending on occupational status, gender, climate, harassment severity, and power differential. Cognitive appraisal mediated the determinant-coping relationship. PMID- 11768059 TI - Are female managers quitters? The relationships of gender, promotions, and family leaves of absence to voluntary turnover. AB - This study examined the relationships of gender, promotions, and leaves of absence to voluntary turnover for 26,359 managers in a financial services organization. Using Cox regression analyses and controlling for human capital, the authors found that, contrary to their prediction, female managers' voluntary turnover rates were slightly lower than those of their male counterparts. Managers who had been promoted were less likely to resign than nonpromoted managers only if the promotion had occurred within the past 11 months, and promoted women were less likely to resign than promoted men. The authors also found that managers who had taken family leaves had higher voluntary turnover rates than managers who had not taken leaves, and among family leave takers, managers with graduate degrees were less likely to resign than managers with less education. PMID- 11768060 TI - Explication of the coping goal construct: implications for coping and reemployment. AB - This longitudinal study developed a reemployment coping goal construct and examined its role in a job-loss context. Several predictors of displaced workers' reemployment coping goal intensity were examined: human capital, employment commitment, internal coping resources, and anticipation of job loss. Results show that human capital, employment commitment, internal coping resources, and anticipation of job loss positively predicted a reemployment coping goal. Human capital also directly predicted reemployment. Finally, unemployed individuals' reemployment coping goal intensity positively predicted job-search effort, which positively predicted reemployment. Implications for the process of coping with job loss and future research are discussed. PMID- 11768061 TI - Minority dissent and team innovation: the importance of participation in decision making. AB - This study integrates research on minority dissent and individual creativity, as well as team diversity and the quality of group decision making, with research on team participation in decision making. From these lines of research, it was proposed that minority dissent would predict innovation in teams but only when teams have high levels of participation in decision making. This hypothesis was tested in 2 studies, 1 involving a homogeneous sample of self-managed teams and 1 involving a heterogeneous sample of cross-functional teams. Study 1 suggested that a newly developed scale to measure minority dissent has discriminant validity. Both Study 1 and Study 2 showed more innovations under high rather than low levels of minority dissent but only when there was a high degree of participation in team decision making. It is concluded that minority dissent stimulates creativity and divergent thought, which, through participation, manifest as innovation. PMID- 11768062 TI - Dimension and exercise variance in assessment center scores: a large-scale evaluation of multitrait-multimethod studies. AB - This study addresses 3 questions regarding assessment center construct validity: (a) Are assessment center ratings best thought of as reflecting dimension constructs (dimension model), exercises (exercise model), or a combination? (b) To what extent do dimensions or exercises account for variance? (c) Which design characteristics increase dimension variance? To this end, a large set of multitrait-multimethod studies (N = 34) were analyzed, showing that assessment center ratings were best represented (i.e., in terms of fit and admissible solutions) by a model with correlated dimensions and exercises specified as correlated uniquenesses. In this model, dimension variance equals exercise variance. Significantly more dimension variance was found when fewer dimensions were used and when assessors were psychologists. Use of behavioral checklists, a lower dimension-exercise ratio, and similar exercises also increased dimension variance. PMID- 11768063 TI - A diagnostic-ratio approach to measuring beliefs about the leadership abilities of male and female managers. AB - This study departed from previous research on gender stereotyping in the leadership domain by adopting a more comprehensive view of leadership and using a diagnostic-ratio measurement strategy. One hundred and fifty-one managers (95 men and 56 women) judged the leadership effectiveness of male and female middle managers by providing likelihood ratings for 14 categories of leader behavior. As expected, the likelihood ratings for some leader behaviors were greater for male managers, whereas for other leader behaviors, the likelihood ratings were greater for female managers or were no different. Leadership ratings revealed some evidence of a same-gender bias. Providing explicit verification of managerial success had only a modest effect on gender stereotyping. The merits of adopting a probabilistic approach in examining the perception and treatment of stigmatized groups are discussed. PMID- 11768064 TI - Bothered by abstraction: the effect of expertise on knowledge transfer and subsequent novice performance. AB - Although experts should be well positioned to convey their superior knowledge and skill to novices, the organization of that knowledge, and particularly its level of abstraction, may make it difficult for them to do so. Using an electronic circuit-wiring task, the authors found that experts as compared with beginners used more abstract and advanced statements and fewer concrete statements when providing task instructions to novices. In a 2nd study, the authors found that beginner-instructed novices performed better than expert-instructed novices and reported fewer problems with the instructions when performing the same task. In Study 2, the authors found that although novices performed better on the target task when instructed by beginners, they did better on a different task within the same domain when instructed by experts. The evidence suggests that the abstract, advanced concepts conveyed by experts facilitated the transfer of learning between the different tasks. PMID- 11768065 TI - Pink triangles: antecedents and consequences of perceived workplace discrimination against gay and lesbian employees. AB - A model of perceived sexual orientation discrimination was tested in a national sample of 534 gay and lesbian employees. The effects of legislation, organizational policies and practices, and work group composition on perceived sexual orientation discrimination were examined, as well as the attitudinal and organizational outcomes associated with discrimination. Gay employees were more likely to report discrimination when employed in groups that were primarily heterosexual and in organizations that lacked supportive policies and were not covered by protective legislation. Disclosure of sexual orientation at work was related to discrimination and antecedent variables. Perceived discrimination was associated with negative work attitudes and fewer promotions. Organizational policies and practices had the strongest impact on perceived discrimination and were directly related to outcomes. PMID- 11768066 TI - Perceived victimization moderates self-reports of workplace aggression and conflict. AB - A sample of 489 employed men between 32 and 36 years old responded to questions concerning rates of having engaged in workplace aggression and conflict. These individuals also completed a personality inventory and questionnaires related to past antisocial behavior and alcohol abuse. Consistent with prior research, workplace aggression and conflict were significantly correlated with particular personality variables (stress reaction, aggression, and control) as well as with general past antisocial behavior and alcohol abuse. Furthermore, these relationships were moderated by the perception of being victimized by others (alienation), with such perceptions strengthening associations between workplace aggression and other risk factors. These interaction effects, which cannot plausibly be attributed to the use of a self-report criterion, could have important implications for understanding and predicting aggression and conflict behavior within organizations. PMID- 11768067 TI - Relationship of core self-evaluations to goal setting, motivation, and performance. AB - A newly developed personality taxonomy suggests that self-esteem, locus of control, generalized self-efficacy, and neuroticism form a broad personality trait termed core self-evaluations. The authors hypothesized that this broad trait is related to motivation and performance. To test this hypothesis, 3 studies were conducted. Study 1 showed that the 4 dispositions loaded on 1 higher order factor. Study 2 demonstrated that the higher order trait was related to task motivation and performance in a laboratory setting. Study 3 showed that the core trait was related to task activity, productivity as measured by sales volume, and the rated performance of insurance agents. Results also revealed that the core self-evaluations trait was related to goal-setting behavior. In addition, when the 4 core traits were investigated as 1 nomological network, they proved to be more consistent predictors of job behaviors than when used in isolation. PMID- 11768068 TI - Mug shot exposure prior to lineup identification: interference, transference, and commitment effects. AB - The effects of viewing mug shots on subsequent identification performance are as yet unclear. Two experiments used a live staged-crime paradigm to determine if interpolated eyewitness exposure to mug shots caused interference, unconscious transference, or commitment effects influencing subsequent lineup accuracy. Experiment 1 (N = 104) tested interference effects. Similar correct decision rates were obtained for the mug shot and no mug shot groups from both perpetrator present and absent lineups. Experiment 2 (N = 132) tested for commitment and transference effects. Results showed that the commitment group made significantly more incorrect identifications than either the control or the transference group, which had similar false-identification rates. Commitment effects present a serious threat to identification accuracy from lineups following mug shot searches. PMID- 11768069 TI - Attributions of the "causes" of group performance as an alternative explanation of the relationship between organizational citizenship behavior and organizational performance. AB - The purpose of this study was to examine the possibility that feedback regarding team performance may influence team members' reports of organizational citizenship behaviors. Ninety-five teams of business students (N = 412) participated in a labor-scheduling simulation over a local area network. Teams were provided with false negative, false positive, or neutral feedback regarding their performance. Results support the hypothesis that the perception of 2 forms of organizational citizenship behavior (helping behavior and civic virtue) in work groups may, in part. be a function of the nature of the performance feedback that group members receive. However, negative feedback appears to play a more critical role than positive feedback in this attributional process. Possible reasons for these findings, as well as their implications, are discussed. PMID- 11768070 TI - Turnover and organizational performance: a comparative analysis of the effects of voluntary, involuntary, and reduction-in-force turnover. AB - Data were collected from 31 regional subunits of a national financial services company to examine differential effects of 3 types of turnover (voluntary, involuntary, and reduction-in-force) on measures of organizational subunit performance. Although each form of turnover exhibited adverse effects on subunit performance when examined separately, partial correlation results revealed greater and more pervasive adverse effects for reduction-in-force turnover (i.e., downsizing) in comparison with the effects of voluntary and involuntary turnover. The results confirm the negative effects of downsizing, suggesting the need to move beyond the traditional voluntary-involuntary classification scheme used in turnover research. PMID- 11768071 TI - One-at-a-time versus grouped presentation of mug book pictures: some surprising results. AB - Eyewitnesses to a simulated crime attempted to identify the perpetrator from a computerized mug book. The 208 mug book pictures were presented either 1 mug shot per page or in groups of 12 mug shots per page. Half of the mug books were arranged by similarity to the perpetrator as determined by a facial recognition algorithm, and half were randomly arranged. In contrast to past findings with photospreads, false-positive identifications were significantly higher using the one-at-a-time procedure than the grouped procedure. Results suggest that the best practice for mug books may be the use of groups of pictures per page rather than the one-at-a-time procedure long advocated by experts for use in lineups and photospreads. PMID- 11768072 TI - The causes of organizational citizenship behavior: a motivational analysis. AB - This study addressed the role of motives in organizational citizenship behavior (OCB). Three motives were identified through factor analyses: prosocial values, organizational concern, and impression management. Scales that measured these motives and other variables known to covary with OCB were administered to 141 municipal employees and were correlated with self-, peer, and supervisor ratings of 5 aspects of OCB. Relative to the other motives, prosocial values motives were most strongly associated with OCB directed at individuals, and organizational concern motives were most strongly associated with OCB directed toward the organization. Each of the motives accounted for unique amounts of variance in OCB. The results suggest that motives may play an important role in OCB. PMID- 11768073 TI - Bayesian analysis of liability of clinical mastitis in Norwegian cattle with a threshold model: effects of data sampling method and model specification. AB - First-lactation records of Norwegian Cattle were used to infer heritability of liability to clinical mastitis with a threshold sire model. Mastitis was defined as a binary response (presence or absence) in a defined period of first lactation (opportunity period). Length of opportunity period (from 30 d before calving up to 120 or 300 d of lactation) had less effect on heritability estimates than data sampling methods (include or exclude records of cows culled before the end of the opportunity period) whereas sire ranking was more affected by the former. Including all cows, whether culled before the end of the opportunity period or not, gave a sharper and more symmetric posterior distribution of heritability of liability to clinical mastitis. When we analyzed data for all cows, model specification had a small effect on heritability estimates, while sire ranking was affected markedly. Posterior means of heritability range from 0.058 to 0.074. A model regressing on the length of the opportunity period for culled cows without mastitis, was shown favorable for the two opportunity periods using Bayes factors and the deviance information criterion for model comparison. This model, in which liability of mastitis depends on time to culling, may allow utilizing information from all first lactations in genetic evaluation, irrespectively of duration and culling outcome. PMID- 11768074 TI - Resistance to freezing and frozen storage of Streptococcus thermophilus is related to membrane fatty acid composition. AB - The resistance to freezing and frozen storage of Streptococcus thermophilus was related to the fatty acid composition of the cell membrane. The effects of four experimental factors were investigated on the fatty acid concentrations and on the recovery of acidification activity of S. thermophilus stored at -20 degrees C by using a complete experimental design: incorporating oleic acid in the culture medium, fermentation pH, addition of glycerol as cryoprotective agent and duration of storage. The acidification activity decreased during the freezing and the frozen storage of S. thermophilus. The storage time slightly enhanced the unsaturated fatty acid concentrations. The addition of glycerol did not modify the fatty acid composition but increased the resistance to frozen storage. The addition of oleic acid and the decrease of the fermentation pH enhanced the ratio unsaturated:saturated fatty acids and improved the recovery of the acidification activity. These results indicate that the resistance to frozen storage was closely related to the membrane fatty acid composition. We interpreted this as an adaptation of S. thermophilus to the addition of oleic acid and the unfavorable growth conditions that corresponded to a low fermentation pH. PMID- 11768075 TI - The liquid-state 31P-nuclear magnetic resonance study on microfiltrated milk. AB - To gain further insight into diversiform phosphorus in bovine milk, we separated skim milk into casein micelle and serum fractions by microfiltration and subjected them to liquid-state 31P-nuclear magnetic resonance (NMR) spectroscopy. As previously reported, the skim milk spectrum showed a broad and indistinct peak from phosphoserine residue (SerP) of casein. In the casein micelle spectrum, however, the SerP peak was more clearly observed with a phosphate peak that may be from micellar calcium phosphate (MCP). The serum spectrum was the same as skim milk spectrum, except for SerP peak. Furthermore, two types of casein micelle fractions, with 0.90 and 1.04 of [beta-casein + kappa-casein]/[alpha(s1)-casein + alpha(s2)-casein] ratios were generated by different temperature microfiltrations, occurring because beta-casein is released from the micelle at a low temperature. The shape of SerP peaks changed dramatically in both the casein micelle spectra, when the temperature dropped from 35 to 5 degrees C. Deconvolution analysis indicated that each SerP peak comprised the same set of four peaks. Half-width and composition discriminated between the two types of casein micelle fractions. As a consequence, there was significant interaction between casein micelle and milk serum, causing cloudiness of SerP in the liquid state 31P-NMR spectrum of milk. Casein composition influenced the SerP-MCP interaction in micellar structure. Shape changing of the SerP peak was discussed in connection with beta-casein-release phenomenon. PMID- 11768077 TI - Small strain oscillatory shear and microstructural analyses of a model processed cheese. AB - The rheological and microstructural properties of a model processed cheese were investigated. The cheese contained 20% protein (rennet casein), 27% anhydrous milk fat, 1.5% NaCl and 1 to 3% Na2HPO4 (DSP). Processing time (10, 20, or 30 min), DSP (1, 2, or 3%) and pH of the DSP-NaCl solution (5.4, 5.6, or 5.8) were adjusted to alter rheological properties. Small-strain oscillatory shear rheological parameters that correlated with transitions previously observed by large-strain (fracture) properties were moduli at 8 degrees C and changes in moduli with cooling from 80 to 25 degrees C. Mechanical spectra at 80 degrees C indicated cheeses containing less than 2.0% DSP were entangled macromolecular dispersions, and those containing more than 2.0% DSP were gels. A compilation of small strain results suggested samples could be divided into three basic rheological states. A model describing the gel network is proposed based on the results of this investigation and large-strain (fracture) rheological properties. The model was based on increased breakdown of para-casein aggregates into amphiphilic molecules and rheological properties being related to the combination of para-casein aggregates and amphiphilic molecules. PMID- 11768076 TI - Reversibility of the temperature-dependent opacity of nonfat mozzarella cheese. AB - Salted and unsalted nonfat mozzarella cheese was made by direct acidification and stored at 4 degrees C over 60 d. Changes in cheese opacity were measured by using reflectance L* values while the cheese was heated from 10 to 90 degrees C, then cooled to 10 degrees C, and reheated to 90 degrees C. A characteristic opacity transition temperature (T(OP)) was obtained for each cheese. Both salt content and storage time influenced T(OP). Opacity during heating, cooling, and reheating formed a hysteresis. At d 1, the unsalted cheese became opaque when heated to 20 degrees C, but the salted cheese required heating to 40 degrees C. As the salted cheese was aged, its T(OP) increased so that by 60 d the cheese did not become opaque until it was heated to 70 degrees C. PMID- 11768078 TI - Physico-chemical properties of skim milk retentates from microfiltration. AB - Physico-chemical properties of retentates obtained from selective concentration of skim milk up to 8 times its original weight using a microfiltration system were studied. The effects of process variables, namely concentration (8.6 to 27 wt.%), temperature (20 to 50 degrees C) and pH (6.0, 6.3, and 6.5) on density (rho), apparent viscosity (mu(a)), consistency coefficient (K), flow behavior index (n), and activation energy (Ea) of the retentates were examined. Depending on pH, retentates showed significant increase in apparent viscosity, deviated from classical Newtonian behavior and exhibited shear-thinning between 11 to 17% solids concentration. No yield stress was detected in the range of concentration studied. The power law parameters (n and K) followed a similar trend. An Arrhenius-type equation described well the effect of temperature on apparent viscosity. Although activation energy increased 120 to 130% for a threefold increase in solids concentration, it was not significantly different from that of other types of concentrated milk at approximately the same concentration. Increasing solids were responsible for change in flow properties with concentration, while the effect of pH was attributed to differential protein (primarily casein) retention and the change in solvation properties and voluminosity of casein micelles. Models relating concentration, temperature, and pH to retentate apparent viscosity and consistency coefficient were identified. Skim milk microfiltration with in-process pH adjustment produces retentates depleted in whey proteins and calcium with significantly altered properties. PMID- 11768079 TI - Compositional effects on milk fat crystallization. AB - Seasonal and regional variability in milk fat composition causes differences in crystallization behavior, which can, for example, result in variability in fractionation efficiency and physical properties of butter. However, the specific compositional causes of variability in milk fat crystallization behavior are still only poorly understood. In this work, the seasonal and regional variations in composition of anhydrous milk fat were analyzed and related to crystallization behavior. Although there were no clear-cut trends in chemical composition (triacylglycerol, fatty acid, and minor lipid profiles) among the milk fats, significant differences in crystallization behavior were observed. For anhydrous milk fat samples made from sweet cream and obtained from the same milk supply through a period of 14 mo, no significant trends in either composition or crystallization behavior were observed. This suggests that seasonal variability of milk fat may be reduced by current feeding strategies in the United States. More detailed examination of the triacylglycerol profiles led to the conclusion that the relative contents of certain triacylglycerol combinations correlated well with crystallization behavior. In particular, the ratio of higher-melting to lower-melting triacylglycerols could be used to predict crystallization behavior. Higher ratios of higher-melting triacylglycerols led to higher crystallization rate. PMID- 11768080 TI - Thermal and structural behavior of anhydrous milk fat. 2. Crystalline forms obtained by slow cooling. AB - The crystallization behavior of milk fat has been examined on slow cooling at 0.1 degrees C/min from 50 to -15 degrees C, to determine the variations of triacylglycerol organizations as a function of temperature. The experiments have been conducted with an instrument allowing coupled X-ray diffraction (XRD) at both small and wide angles and high-sensitivity differential scanning calorimetry (DSC) recordings from the same sample by taking advantage of the high-energy flux of a synchrotron. On slow cooling, milk fat triacylglycerols sequentially crystallize in four different lamellar structures with double-chain length of 41.5, 48.3, and 39.2 A and a triple-chain length of 62.2 A stackings. Simultaneous wide-angle XRD has shown that initial nucleation occurs in a packing of beta' type at about 24 degrees C. For temperature < 13 degrees C, triacylglycerols crystallize in an hexagonal subcell of alpha type, leading to the coexistence of the beta' + alpha polymorphic forms, which is recorded until 15 degrees C. Thermal analysis allowed to correlate the formation of the different crystalline species monitored by XRDT (XRD as a function of temperature) to the exothermal events recorded simultaneously by differential scanning calorimetry. The evolution of the species formed during crystallization was also monitored on heating at 2 degrees C/min. The absence of polymorphic evolution on heating, as well as the high final melting point observed, about 40 to 41 degrees C, confirmed that cooling at 0.1 degrees C/min leads to quasi equilibrium. PMID- 11768081 TI - Effect of time of insemination on number of accessory sperm, fertilization rate, and embryo quality in nonlactating dairy cattle. AB - Two experiments were conducted to determine the effect of insemination time on number of accessory sperm per embryo (ovum), fertilization rate, and embryo quality. Semen was collected from three fertile Holstein bulls and cryopreserved in egg yolk-citrate-glycerol. In experiment 1, cows were continuously monitored for behavioral estrus by the HeatWatch estrous detection system and were artificially inseminated (AI) with one 0.5-ml straw (25 x 10(6) sperm) at the onset of estrus (AI 0 h), 12 h after onset (AI 12 h), or received natural service at 0 h (Nat 0 h) from one of three bulls. From 150 inseminations, 115 embryos and ova (AI 0 h: n = 39; AI 12 h: n = 39; Nat 0 h: n = 37) were recovered 6 or 7 d after insemination. Fertilization rates differed between treatments (AI 0 h: 67%; AI 12 h: 79%; Nat 0 h: 98%). Median accessory sperm per embryo (ovum) also differed (AI 0 h: 1; AI 12 h: 10; and Nat 0 h: 27) and paralleled the fertilization rate. Embryo quality was not affected by insemination time or natural service. In experiment 2, cows received AI at 0, 12, or 24 h (AI 24 h) after the onset of estrus as determined by HeatWatch. From 154 inseminations, 117 embryos and ova (AI 0 h: n = 39; AI 12 h: n = 39; AI 24 h: n = 39) were recovered 6 or 7 d after insemination. Fertilization rates did not differ in experiment 2 (AI 0 h: 66%; AI 12 h: 74%; AI 24 h: 82%); however, a trend toward a higher fertilization rate accompanied AI 24 h. Median accessory sperm values increased from AI 0 h (1) to AI 24 h (4). Embryo quality declined with AI at increasing intervals after onset of estrus, as percentages of excellent and good, fair and poor, and degenerate embryos were as follows: 77, 15, 8; 52, 38, 10; and 47, 19, 34 for the 0-, 12-, and 24-h inseminations, respectively. Results indicate AI 12 h after the onset of estrus provides a compromise between potential fertilization failure (AI 0 h) and embryo failure (AI 24 h), despite increased accessory sperm per embryo (ovum) after AI 24 h. Artificial insemination 12 h after onset of estrus should optimize fertility of dairy cattle through an acceptable fertilization rate, number of accessory sperm per embryo, and desirable embryo quality. PMID- 11768082 TI - Phylogenetic studies on Corynebacterium bovis isolated from bovine mammary glands. AB - Coryneform bacteria are frequently isolated from bovine mastitis with the lipophilic species, and Corynebacterium bovis is the most frequently isolated organism of this group. However, previous studies on the phylogeny of corynebacteria have incorporated only a single reference strain. We examined the phylogeny of C. bovis using 47 strains isolated from bovine mammary glands. Phylogenetic studies were performed by direct sequencing of the 16S ribosomal RNA and comparison to sequences of reference strains. All strains identified as C. bovis demonstrated similarity of 98% or higher to the ribosomal RNA gene sequences of the type strain of C. bovis. Phylogenetic analyses indicated that all strains tested clustered with members of the Corynebacterium urealyticum group confirming that C. bovis is a legitmate member of the genus Corynebacterium. Further investigation into the diversity within the species using repetitive element palindrome PCR indicated only minor differences between the strains tested. Corynebacterium bovis ATCC 13722 demonstrated the highest similarity (95%) with Brevibacterium helvolum, indicating that this organism does not belong in the genus Corynebacterium. PMID- 11768083 TI - The effects on production and behavior of mixing uniparous and multiparous cows. AB - The production and behavior of a group of eight multiparous and eight uniparous cows after they were mixed were compared with unmixed groups of 16 multiparous and 16 uniparous cows. The cows grazed pasture (mean height 16 cm) in treatment groups in a daily paddock rotation. The milk yield of mixed cows was 3% less in the first week than cows in the unmixed groups, and 1% less in the 6 wk after mixing. The reduction in milk yield was similar for uni- and multiparous cows. Both uni- and multiparous cows in the mixed group grazed for less time and they stood for longer, particularly in the first week postmixing. The multiparous cows in the mixed group increased their pasture biting rate and became more dominant than the uniparous cows, who spent more time grooming other cows and in aggressive interactions compared with the unmixed group of uniparous cows. We concluded that the mixing of multi- and uniparous cows causes disruption to their grazing and social behavior, which results in a reduction in milk yield. PMID- 11768084 TI - Effect of somatotropin on thyroid hormones and cytokines in lactating dairy cows during ad libitum and restricted feed intake. AB - Twelve Holsteins in first lactation were used to investigate the relationship between energy balance and effects of bovine somatotropin (bST) on thyroid hormone metabolism and cytokine concentrations in serum. Six cows were fed for ad libitum intake and six cows were feed restricted to induce negative energy balance during two treatment periods of 6 d. During treatment periods, cows were administered vehicle or 40 mg of bST/d according to a crossover design. Between treatment periods was a 15-d recovery period, during which all cows were fed ad libitum. Cows that were fed ad libitum remained in positive energy balance during control and bST treatments, whereas cows that were fed for restricted intake were in negative energy balance during control and bST treatment periods. In both dietary groups, bST decreased energy balance. Milk production and the fat percentage of milk increased during bST treatment in both dietary groups. Fat corrected milk yield was increased 13% by bST treatment. Serum concentrations of IGF-I did not differ between dietary groups but were greater during bST than control periods. Serum thyroxine concentration was decreased by bST treatment. Serum triiodothyronine and reverse-triiodothyronine were not altered by hormone treatment, but circulating concentrations of thyroid hormones were apparently reduced by dietary restriction. Neither hepatic nor mammary thyroxine 5' deiodinase was affected by bST treatment. Plasma concentration of tumor necrosis factor-alpha, a potential regulator of thyroxine 5'-deiodinase, was not affected by bST treatment. Short-term treatment with bST did not influence thyroid hormone metabolism in lactating cows in positive or negative energy balance. PMID- 11768085 TI - Relationships among dietary roasted soybeans, milk components, and spontaneous oxidized flavor of milk. AB - Relationships among dietary roasted whole soybeans (RSB), milk fatty acid profile, and the development of spontaneous oxidized flavor of milk were investigated by using 20 commercial dairy herds. Diets contained 0 to 15.3% of dry matter as RSB. Concentrations of dietary RSB were correlated positively with concentrations of C18:2 and C18:3 in milk fat. Concentrations of alpha tocopherol, beta-carotene, and ascorbic acid in milk decreased from 0 to 3 d of storage (4 degrees C), and oxidized flavor in milk increased linearly between 0 and 8 d of storage. Milk fatty acid profile did not change during storage. The development of oxidized flavor at 8 d postsampling was correlated (r) with increased concentrations in milk fat of C18:2 (0.49), C18:3 (0.55), total polyunsaturated milk fatty acids (0.50), and dietary concentrations of RSB (0.38). Multiple regression was used to quantify relationships between variables and oxidized flavor (samples stored 8 d). All significant models included milk concentrations of Cu and dehydroascorbic acid. Concentrations of C18:2, C18:3, or total polyunsaturated fatty acids in milk fat, or dietary RSB concentrations, and interactions of those variables with Cu were included in individual models. Milk with high concentrations of polyunsaturated fatty acids and Cu were most susceptible to oxidation. Feeding RSB increased polyunsaturated fatty acid concentrations in milk fat, which increased the likelihood of oxidized flavor, especially when milk had high concentrations of Cu. PMID- 11768086 TI - Effects of a nonforage diet on milk production, energy, and nitrogen metabolism in dairy goats throughout lactation. AB - The objective of the experiment was to compare a silage-based control diet (C) with a nonforage diet (NF) in dairy goats throughout lactation in terms of animal performance and energy utilization. Eight Saanen goats were divided into two groups and fed C or NF, a commercial blend that included sunflower meal, cassava, coconut meal, and whole cottonseeds as the main ingredients that was characterized by a small particle size and a high crude protein content. In early, mid, and late lactation (44, 100, and 219 days in milk) the goats were individually tested for dry matter intake (DMI), digestibility, milk yield and composition, milk renneting properties, rumen and plasma parameters, and nitrogen and energy utilization (open circuit respiration chambers). During early and mid lactation, the NF fed goats had a very high DMI: 2946 and 2915 g/d, respectively. Nevertheless, milk yield was similar for the two treatments: 4369 vs. 4342 and 3882 vs. 3841 g/d for goats fed diets C and NF during the first and second periods, respectively. Milk fat content was not statistically different between the two diets. The protein content and rheological parameters of milk were similar for the two diets. Nonprotein nitrogen and urea levels in milk of goats fed NF were significantly higher than goats fed C. Ruminal ammonia and plasma urea nitrogen were also significantly increased by diet NF, due to its high protein content. Plasma glucose, beta-hydroxybutyrate, and nonesterified fatty acids and ruminal volatile fatty acids were not influenced by dietary treatment. Dietary NF significantly decreased energy digestibility (74.5 vs. 65.8%, on average for the lactation, for C and NF, respectively) and had a significantly lower metabolizability (metabolizable energy/intake energy; 66.6 vs 58.0%, on average); however, the efficiency of utilization of metabolizable energy was unaffected by the diet. In conclusion, goats were fed a nonforage diet during the entire lactation without detrimental effect on their health and productive performance. PMID- 11768087 TI - Supplementing pasture to lactating Holsteins fed a total mixed ration diet. AB - Beginning in September 1997, a 6-week study was conducted to compare performance and income-over-feed cost of lactating Holsteins cows fed either a total mixed ration diet (TMR) only, compared to TMR in the afternoon and pasture in the morning, or TMR in the morning and pasture in the afternoon. Fifty-four Holstein cows in midlactation, averaging 28.1 kg/d of milk, were used in the study. Cows were on pasture for 8 h/d after either the p.m. or the a.m. milking. Predominantly orchardgrass with lesser amounts of white clover and Kentucky bluegrass were grazed. Pasture was sampled once per week, and weekly composites were analyzed. Compressed sward height and herbage dry matter (DM) yield were estimated once per week. Milk yield was electronically recorded and was sampled biweekly. Body condition score and body weight (BW) was recorded at the beginning and end of the study. Income-over-feed cost was calculated for each treatment. Compressed sward height and DM yield averaged 12.7 cm and 1397 kg/ha, respectively. Pasture crude protein, neutral detergent fiber, and acid detergent fiber averaged 27.0, 55.7, and 26.9%, respectively, and net energy-lactation was 1.65 Mcal/kg of dry matter. Milk production was greater for cows on the TMR treatment (29.1 vs. 28.2 and 27.6). No significant difference occurred in percentage of milk fat (3.54, 3.42, and 3.46%), or protein (3.28, 3.20, and 3.22%) for the above respective treatments. The SNF content (8.77 vs. 8.67 and 8.63%) was higher in TMR cows. While BW change did not differ among treatments (23, 32, and 22 kg), body condition score change was greater in cows fed TMR only (0.14 vs. -0.06 and 0.01). As expected, TMR intake was greatest for cows fed TMR only and lowest for cows grazing after the p.m. milking (26.6 vs. 20.3 vs. 17.5 kg/d dry matter). Income-over-feed cost differed between treatments and was approximately 18.6 and 7.5% higher for cows grazing high quality pasture during the afternoon and the morning, respectively, compared with cows on the TMR treatment. PMID- 11768088 TI - Ruminal fermentation and intestinal flow of nutrients by lactating cows consuming brown midrib corn silages. AB - Rumen characteristics and digestive kinetics of brown midrib corn silage were evaluated with five late-lactation (221 DIM +/- 20 d) multiparous cows fitted with ruminal and duodenal cannula. Dietary treatments were applied by using a single reversal design with two 21-d periods where either brown midrib (BM3) or isogenic (ISO) corn silage were included in a total mixed ration formulated to be 40% concentrate and 60% corn silage on a dry matter (DM) basis. Rumen and total tract digestibilities of DM, organic matter, neutral detergent fiber, acid detergent fiber, starch, and N were determined and rumen characteristics evaluated. Apparent rumen DM and organic matter digestibilities were greater for the BM3 corn silage (7.1 and 4.7 percentage units, respectively). Dietary intake and duodenal flow of starch were greater and rumen and total tract starch digestibilities were lower for BM3 corn silage diets than ISO corn silage diets. However, more starch (1.1 kg/d) was apparently digested and absorbed postruminally in cows fed the BM3 corn silage diets. Duodenal flow of neutral detergent fiber was 0.9 kg/d lower, and ruminal (15.9 percentage units) and total tract digestibilities (4.4 percentage units) were higher for BM3 treatment compared with the ISO treatment. Digestive patterns of ADF were similar for the BM3 and ISO treatments. Ruminal pH was lower in the cows fed the BM3 corn silage than those fed the ISO corn silage. As a result of a tendency for decreased N excretion in urine and slight increases in N intake due to increased DM intake, N balance tended to be greater for the BM3 treatment compared with the ISO treatment. These results may partially explain the benefits of feeding BM3 corn silage to cows during early lactation, as the observed increases in fiber component digestibility and improved N economy may combine to enhance DM intake and better support the nutritional demands of milk production for the high producing dairy cow. PMID- 11768089 TI - Evaluation of wet corn gluten feed in diets for lactating dairy cows. AB - Two experiments were conducted to evaluate responses of primiparous and multiparous Holstein cows to diets containing wet corn gluten feed (WCGF). In both experiments, WCGF replaced a mix of alfalfa hay, corn silage, and corn grain. In experiment 1, 32 primiparous Holstein cows (four pens with eight cows/pen) were used in two 2 x 2 Latin squares with 28-d periods. Cows were housed in free stalls and fed diets containing 0 or 20% WCGF dry matter (DM) basis. Cows fed WCGF consumed more DM and produced more energy-corrected milk (ECM) than controls. Production efficiency (ECM/DM intake) was not affected, but yield of milk components was improved by WCGF. In experiment 2, 24 multiparous Holstein cows were used in six 4 x 4 Latin squares with 28-d periods to determine the optimal dietary inclusion rate for WCGF. Cows were housed in a tie-stall barn and fed a total mixed ration twice daily. Treatments were 0, 20, 27.5, and 35% WCGF (DM basis). Cows fed WCGF produced more ECM than controls, but ECM did not differ among cows fed WCGF diets. Cows fed 20 and 27.5% WCGF consumed more DM as a percentage of body weight than those fed either 0 or 35% WCGF. Cows fed WCGF produced ECM more efficiently than controls. Percent milk fat was lower, but fat yield was not different when WCGF was added to diets. Milk protein and lactose yields were higher when WCGF was fed. Plasma glucose, alpha-amino N, and triglyceride concentrations were similar among diets in both experiments, but plasma urea N was higher for cows fed WCGF in experiment 2. PMID- 11768090 TI - Differences in yields of microbial crude protein from in vitro fermentation of carbohydrates. AB - The yield of microbial crude protein (CP) from carbohydrate fermentations was examined using trichloroacetic acid (TCA) precipitation of batch cultures. The medium contained ammonium bicarbonate, casein acid hydrolysate, and cysteine hydrochloride as nitrogen sources. Isolated bermudagrass neutral detergent fiber (iNDF) and 60:40 blends of iNDF and sucrose (Suc), citrus pectin (Pec), or corn starch (Sta) (approximately 375 mg of substrate organic matter/vial) were fermented in vitro in two separate fermentation runs with mixed ruminal microbes. Three fermentation tubes for each substrate were destructively sampled at 0, 4, 8, 12, 16, 20, and 24 h. Fermented samples were precipitated at a concentration of 19.4% TCA, and filtered to collect unfermented iNDF and precipitate. Collected residues were analyzed for CP as Kjeldahl N x 6.25. Microbial CP (TCACP) was estimated as TCA-precipitated CP corrected for the TCA-precipitated CP content of substrates at 0 h, and the mean of fermentation blanks from each hour. Medium pH did not decline below 6.49 in any fermentation tube. Comparisons of maximal yields based on the hour in which the measured mean yield was greatest for each substrate in each fermentation indicated that Sta > Suc = Pec > iNDF (P < 0.05). All substrates showed increases in TCACP to their maxima, followed by declines in TCACP. This likely reflects the relative dominance of production or degradation of microbes about the point of substrate limitation. Unlike other substrates, Suc had no detectable lag, and presented a more persistent TCACP yield curve than the other non-NDF carbohydrates (NFC). Regression analysis of TCACP yield over time for iNDF versus other substrates, Pec + Sta versus Suc, and Pec versus Sta indicated that the compared curves were not parallel (P < 0.05). The patterns of TCACP yield over time were cubic for iNDF and Suc, and quartic for Pec and Sta. The maximal yields of TCACP predicted from the regressions were Sta: 34.0 mg at 15.6 h, Pec: 29.9 mg at 13.5 h, Suc: 25.5 mg at 12.6 h, and iNDF: 13.6 mg at 19.3 h. The NDF and NFC carbohydrates examined differed in both maximal yields and temporal patterns of yield of TCACP. PMID- 11768091 TI - Effect of ensiling alfalfa at low and high dry matter on production of milk used to make Grana cheese. AB - The effect of alfalfa ensiled in bunker silos at high moisture [HM, 34% dry matter (DM)] and low moisture (LM, 56% DM) content on milk production and Grana Padano cheese quality was studied. Forty Italian Friesian lactating cows were allotted to two groups and fed, in a crossover design experiment, two corn silage based diets containing 27% of the total DM as HM or LM. Each of the two periods included 10 d of adaptation and 3 experimental weeks. Forage was cut in the mid vegetative stage with, on average, 34% neutral detergent fiber and 19% crude protein (DM basis). The two alfalfa silages showed a different fermentation pattern with 4.04 and 1.25% of lactic acid, 1.95 and 0.42% of acetic acid, 9.1 and 4.8% of total N ammonia-N for HM and LM, respectively. No butyric acid was found. Clostridial spores and yeast showed no growth in both silages except in the first 2 wk of the experiment where slight aerobic deterioration occurred. The HM treatment resulted in slightly lower DM intake (19.3 vs. 19.9 kg/d) and milk protein content (3.33 vs. 3.38%), higher milk fat content (3.56 vs. 3.37%), and 4% fat-corrected milk (25.7 vs. 24.4 kg/d). Totally, 38 cheeses obtained from over 19 tons of milk with an average yield efficiency of 6.8%, were produced. The milk renneting and microbiological properties and the cheese quality were not significantly different between treatments. However, both treatments had on average 40% of low quality (butyric fermentation) cheeses observed mainly in the first 2 wk of the experiment, when the number of clostridial spores found in alfalfa silages was significantly higher than in the subsequent weeks. The data obtained suggest that the microbial quality of milk depends more on careful management and monitoring all of the steps in milk production, from silage harvest through to cheese making, than on the moisture level of alfalfa silage, provided that the latter is in a range of 35 to 55% DM. PMID- 11768092 TI - Effect of mechanical processing and fat removal on the nutritive value of cottonseed for lactating dairy cows. AB - In experiment 1, 24 midlactation, multiparous Holstein cows were used in six 4 x 4 Latin squares to evaluate extruded-expelled cottonseed (EEC) as a source of ruminally undegradable protein (RUP). Diets were formulated to contain: 16% crude protein (CP), 35% RUP (SBM16); 18% CP, 35% RUP (SBM18); 16% CP, 40% RUP using EEC (EC16); and 16% CP, 40% RUP using a fishmeal-blood meal blend (FBM16). Milk yields (37.2 kg/d) and percentages of milk fat, protein, casein, and SNF were similar across diets. Cows fed FBM16 consumed less dry matter (DM) (28.0 kg/d) than those consuming other diets (29.4 kg/d). In experiment 2, 18 midlactation, multiparous Holstein cows were used in six 3 x 3 Latin squares to determine the value of EEC as a replacement for whole cottonseed in lactating cow diets. Diets contained whole cottonseed (CS), EEC plus tallow (ECT), or EEC (EC). Diets were formulated to be similar in energy, N, and RUP. Milk yields (35.5 kg/d), DM intake (27.0 kg/d), and milk fat percent were similar across diets. Percentages of milk protein and SNF were higher for EC than CS or ECT. These production data suggest that EEC can replace whole cottonseed in isocaloric diets and can be partially substituted for soybean meal or a fishmeal-blood meal blend without affecting lactational performance. In situ ruminal degradation and in vitro ammonia N release indicate that processing of EEC was inadequate to protect the protein from ruminal degradation and EEC would not be a source of RUP. PMID- 11768093 TI - Lactation responses to sulfur-containing amino acids from feather meal or rumen protected methionine. AB - The objectives of this experiment were to determine: 1) if Cys in hydrolyzed feather meal (HFM) can contribute to the supply of sulfur amino acids for meeting requirements of dairy cows; 2) if the feeding value of meat and bone meal (MBM) can be enhanced by HFM or ruminally protected Met (rpMet); and 3) the value of HFM sulfur amino acids relative to rpMet. Fifteen multiparous Holstein cows were used in a replicated 5 x 5 Latin square design with 21-d periods. The control (CTRL) diet was designed to contain feeds that were low in RUP and Met and consisted of 50% alfalfa silage and 50% corn-based concentrate. Additional treatments were modifications of CTRL in which MBM (4% of DM), MBM + rpMet (Smartamine M) (4 and 0.08% of DM), MBM + HFM (4 and 2% of DM), and MBM + rpMet + HFM (4, 0.04, and 1% of DM) replaced corn grain. Feeding MBM depressed milk and 3.5% fat-corrected milk (FCM) yields. Adding rpMet to MBM enhanced dry matter intake, milk and 3.5% FCM yields, and milk crude protein percentage. Milk fat percentage and 3.5% FCM yield were increased when HFM and rpMet were added to MBM. Supplementing HFM to a diet containing MBM could not duplicate the response of adding rpMet to MBM. Results of this study indicate that feeding HFM may not alleviate Met deficiency in lactating dairy cows. PMID- 11768094 TI - Impact of paternity errors in cow identification on genetic evaluations and international comparisons. AB - The impact of paternity identification errors on US genetic evaluations and international comparisons of Holstein dairy bulls for milk, fat, and protein yields was investigated. Sire identification was replaced for 11% of Holstein cows that were sired by AI bulls and had records in the US database for national genetic evaluations; US evaluations were computed based on those modified pedigrees and compared with official national evaluations. Estimated breeding values from the data with introduced paternity errors were biased, especially for later generations. Estimated genetic trends decreased by 11 to 15%. Estimates of standard deviations of sire transmitting ability also decreased by 8 to 9%. International multitrait across-country comparisons of bulls were computed based on national evaluations from the United States, Canada, New Zealand, and The Netherlands. Estimates of genetic correlations between the United States and other countries decreased by 0.04 to 0.06 when US evaluations were based on modified pedigree. The resulting bias toward selection of domestic bulls and the inability to identify truly superior animals that are available internationally could decrease potential selection differentials by 0.07 to 0.09 standard deviation units on the US scale, which corresponds to sire breeding values of approximately 50 kg for milk, 3 kg for fat, and 1.7 kg for protein. Losses for the other countries were lower and ranged from 0.02 to 0.05 standard deviation units, because a correlation of less than unity with the United States decreased the impact of US cow paternity errors on the scales of other countries. Although paternity verification is desirable and technically feasible, commercial implementation would require low testing costs. PMID- 11768095 TI - Characterization of dairy production systems in countries that participate in the International Bull Evaluation Service. AB - The International Bull Evaluation Service Centre has routinely calculated international dairy sire evaluations since 1994. Production systems vary between countries and between herds within a country, and these differences can cause significant genotype x environment interactions. First-lactation records of Holstein cows calving from January 1, 1990 through December 31, 1997, were used in this study. Countries that provided data for this study included Australia, Austria, Belgium, Canada, Czech Republic, Estonia, Finland, Germany, Hungary, Ireland, Israel, Italy, The Netherlands, New Zealand, South Africa, Switzerland, and the United States. Country means were calculated for 13 variables related to climate, herd management, and genetic background. These variables were considered as possible causes of genotype by environment interaction. Highest peak yields were found in Israel and the United States at 31.4 and 30.5 kg, respectively. New Zealand and Estonia had the lowest daily peak yields at 17.1 and 18.9 kg, respectively. This was consistent with genetic differences between these countries, because Israel had the highest average predicted transmitting abilities (PTA) milk among sires, while Estonia had the lowest PTA milk. Persistency of lactation, defined as milk yield at 240 d postpartum divided by milk yield at 60 d postpartum, was highest in the Czech Republic and Estonia at 1.34, and lowest in Israel at 1.05. Herd size also varied substantially between countries, ranging from 2.3 first-lactation cows per herd-year in Finland to 62 per herd-year in Hungary. In summary, tremendous variation exists between the leading dairy countries in management, genetic, and climatic factors. PMID- 11768096 TI - A genome scan to identify quantitative trait loci affecting economically important traits in a US Holstein population. AB - Quantitative trait loci affecting economically important traits were studied for eight large US Holstein grandsire families by using the granddaughter design. A total of 155 microsatellite markers located throughout the bovine genome were selected for the scan. The data analyzed include genotypes for 50 markers not previously reported. Results analyses of 105 marker genotypes reported previously were updated. Effects of marker alleles were analyzed for 38 traits including traits for milk production, somatic cell score, productive life, conformation, calving ease, and 16 canonical traits derived from conformation and production traits. Permutation tests were used to calculate empirical traitwise error rates. A traitwise critical value of P = 0.1 was used to determine significance. Ten putative quantitative trait loci associated with seven of the new markers were identified within specific families. One marker on chromosome 14 was associated with differences in fat yield, fat percentage, and a canonical production trait in two families. Markers on chromosomes 18 and 22 were associated with differences in rump angle in the same family. Markers were associated with differences in udder depth and fore udder attachment on chromosomes 16 and 20, respectively. One marker on chromosome 27 was associated with a difference in the dairy capacity composite index, and another marker on chromosome 13 was associated with a difference in a canonical conformation trait. These additional markers complete our genome scan to identify quantitative trait loci affecting economically important traits in a selected commercial Holstein population. The quantitative trait loci identified in this genome scan may be useful for marker assisted selection to increase the rate of genetic improvement on traits such as disease resistance and conformation traits associated with fitness while accelerating genetic improvement for production. PMID- 11768097 TI - Relationship of somatic cell score with fertility measures. AB - Dairy Herd Improvement data from 284,450 cows in 37 states were used to examine the relationship of test-day somatic cell score, herd, calving year, parity, lactation stage, and calving ease score with fertility measures (rate of nonreturn to estrus by 70 d after first service, days to first service, and days open) for US Holsteins and Jerseys. Factors other than somatic cell score were examined to ensure that the estimation of the effect of somatic cell score was independent of other effects. Nonreturn rates were highest during April and May and lowest during June. Parity had a large effect on nonreturn rate, which was 6 to 7% higher for first parity than for sixth parity and later. Effect of lactation stage at first service on nonreturn rate was large; nonreturn rate increased by 8 to 13% from early to late lactation. Effect of calving ease score on nonreturn rate also was large: a 7% decline in nonreturn rate from score 1 to 5. For Holsteins, a small linear regression was found for nonreturn rate on preceding test-day somatic cell score, but this relationship was not significant for Jerseys. The magnitude of the effect of somatic cell score on fertility traits does not warrant postponing first service when somatic cell score is high. PMID- 11768098 TI - Heritability of teat-end shape and the relationship of teat-end shape with somatic cell score for an experimental herd of cows. AB - Teat-end shapes were categorized for 1443 Holstein cows with 3582 lactations, in the Iowa State University herd at Ankeny, approximately 40 d postpartum between 1970 and 1995. Frequencies of teat-end shapes were as follows: round, 52.2%; prolapsed, 0.8%; flat, 14.2%; plate, 3.4%; funnel, 8.9%; and mixed, 20.5%. Cows were coded as mixed if all four teat-end shapes were not the same. Heritability estimates were obtained with an animal model with pedigrees traced back to registration numbers roughly conforming to birth year 1955. The heritability estimates for first, second, and third and later lactations were 34, 21, and 13%, respectively. Lactation averages for linear somatic cell scores were adjusted for days in milk, and month and age at calving, and were available for 255 cows with 431 lactations categorized from 1992 to 1995. Frequencies of teat-end shape on the 255 cows were as follows: round, 58%; prolapsed, 3%; flat, 11%; plate, 2%; funnel, 6%; and mixed, 20%. Least-squares means of somatic cell score for categories of teat-end shape were computed from a mixed model that included year, parity, and teat-end shape as fixed effects and cow as a random effect. Teat-end shape did not significantly affect somatic cell score. PMID- 11768099 TI - Impact of area and sire by herd interaction on heritability estimates for somatic cell count in Italian Holstein Friesian cows. AB - The aim of the paper was to estimate variance components for somatic cell scores for Italian Holsteins using data from three different areas of the country. A total of 2,202,804 first-parity test-day records, collected from 1990 to 1997 in three areas of Italy (Mantova, Milano, and Parmigiano cheese area), were available for study. The areas differ in herd size, feeding systems and especially in milk use. A minimum standard of quality is also required by some specific methods of cheese production, as for example from the Parmigiano Reggiano cheese chain. These reasons, taken together, affect the attention given to the quality of milk production in herds, and, therefore, to the sanitation levels. A pedigree file was extracted from the national database of Holstein Friesian breed. For computational reasons, eight samples of the data were extracted per area. Variance components were estimated by sample using two different test-day repeatability models. The first model included fixed effects of herd-test date, days in milk (30-d intervals) and calving month, and random effects of permanent environment, additive genetic and residual error. Estimated heritabilities in the first model ranged from 0.06 to 0.09 and repeatabilities from 0.36 to 0.45. Only small differences were detected among areas. In the second model, a random sire x herd interaction effect was added. Including the sire x herd effect resulted in heritability estimates ranging between 0.05 and 0.08 and repeatabilities from 0.35 to 0.45. The analysis revealed that only a small fraction of the total variance (0.35 to 1.5%) could be explained by sire x herd interaction effect. Based on this research, it appears that parameter estimates for somatic cell count do not differ by region, and inclusion of a sire x herd interaction effect is unnecessary. PMID- 11768100 TI - Economic and environmental impact of four levels of concentrate supplementation in grazing dairy herds. AB - Low-cost, pasture-based forage systems are a viable management alternative for small to moderately sized dairy farms in the Northeast United States. A whole farm analysis was conducted to evaluate the potential long-term environmental impact and economic benefit of varying the level of concentrate supplementation on seasonal grazing dairies. A representative dairy farm was simulated with various production strategies over 25 yr of historical Pennsylvania weather using the Dairy Forage System Model. A representative grazing farm (81 ha) was simulated with four levels of daily concentrate supplementation: 1) no supplement, 2) 3 kg of DM/cow in early lactation, 3) 6 kg of DM/cow in early lactation, and 4) 9 kg of DM/cow in early lactation fed daily to the lactating cows to meet annual milk production levels of 5000, 6068, 6968, and 7700 kg/cow, respectively. These farm systems were then compared to an alfalfa- and corn-based confinement system on the same land base where total mixed rations were fed to maintain an annual milk production level of 9000 kg/cow. The five systems were simulated for three scenarios. In the first, total milk sold per farm (625,000 kg) was similar across all systems. In the second, cow numbers were held constant across all systems (100 mature cows), and total milk sold per farm varied. In the third, stocking rate was set so that forage consumed equaled forage production on the farm. Profitability increased as supplementation level increased in the grazing systems, but at a decreasing rate with each successive level of supplementation. At higher levels of supplementation, the grazing dairy farms showed greater profitability than the confinement systems. Economic risk or year to-year variation also decreased as concentrate supplementation level increased. The grazing systems showed an environmental benefit compared with the confinement systems by decreasing nitrogen leaching losses. Concentrate supplementation of grazing lactating dairy cows provided an increase in profitability and a mixed impact on nutrient balance of the farm. PMID- 11768101 TI - Efficiency and competitiveness of the small New York dairy farm. AB - Many believe that small dairy farms cannot survive because costs of production per cwt of milk are thought to be higher than the cost of production per cwt of milk on larger farms. Raw summaries of dairy farm business records in New York are consistent in that smaller dairy farms do have higher average costs of production. However, 1999 data from a group of 314 New York dairy farms were used to model costs of production as frontier or best practice costs with a separate efficiency component accounting for use of projected best practices. That modeling procedure showed that most of the empirical high cost observed on many small dairy farms is due to inefficiency. Therefore, efficient small dairy farms can be competitive with larger dairy farms in New York in producing milk at comparable costs per unit. The frontier cost of production for a 50-cow farm was $13.61 per hundred pounds (45.5 kg) or $0.299 per kg, only slightly over 4% more than costs for a 500-cow farm ($13.03 per hundred pounds or $0.287 per kg). The implication is that the efficient small dairy farm can compete with the efficient large dairy farm. PMID- 11768102 TI - Effects of P.G. 600 on the onset of estrus and ovulation rate in gilts treated with Regu-mate. AB - Three experiments assessed the onset of estrus and ovulation rate in gilts treated with gonadotropins after the withdrawal of an orally active progestin. In Exp. 1, all cycling gilts received the progestin (Regu-mate; Intervet America Inc., Millsboro, DE) at a rate of 15 mg/d for 18 d. Twenty-four hours after the last feeding of Regu-mate, 32 gilts received an i.m. injection of 400 I.U. PMSG and 200 I.U. hCG (P.G. 600, Intervet America, Inc.), and 32 gilts received an i.m. injection of deionized water. The percentage of gilts displaying estrus < or = 7 d (P = 0.64) and the injection-to-estrus interval (P = 0.37) were similar for P.G. 600-treated gilts (93.8% and 4.1 +/- 0.1 d) and controls (90.6% and 4.3 +/- 0.1 d). Ovulation rate was greater (P < 0.01) in P.G. 600-treated gilts (28.8 +/- 1.1) compared with controls (17.4 +/- 1.1). In Exp. 2, 58 cycling gilts received Regu-mate (15 mg/d) for 18 d. Twenty-four hours after Regu-mate withdrawal, gilts received i.m. P.G. 600 or water (n = 29/treatment). Gilts were bred via AI 12 and 24 h after first detection of estrus. The percentage of gilts displaying estrus < or = 7 d (P = 0.45) and the injection-to-estrus interval (P = 0.27) were similar for P.G. 600-treated gilts (82.7% and 4.0 +/- 0.1 d) and controls (89.7% and 4.2 +/- 0.1 d). Ovulation rate was greater (P < 0.01) in P.G. 600-treated gilts (26.2 +/- 1.8) compared with controls (18.1 +/- 1.7). Pregnancy rate (P = 0.71) and the number of live embryos at d 30 postmating (P = 0.40) were similar for P.G. 600 treated gilts (91.7% and 15.6 +/- 1.2) and controls (88.5% and 14.1 +/- 1.2). In Exp. 3, prepubertal gilts (142.6 +/- 0.7 d of age) received Regumate (15 mg/d) (n = 20) or a control diet not including Regu-mate (n = 20) for 18 d. Twenty-four hours after Regu-mate withdrawal, all gilts received i.m. P.G. 600. The percentage of gilts displaying estrus < or = 7 d (P = 0.49) and the P.G. 600-to estrus interval (P = 0.69) were similar for Regu-mate-fed gilts (95% and 4.3 +/- 0.2 d) and controls (88.9% and 4.2 +/- 0.2 d). Ovulation rate was similar (P = 0.38) for Regu-mate fed gilts (16.6 +/-1.6) and controls (14.4 +/- 1.8). In cycling gilts, administration of P.G. 600 after withdrawal of Regu-mate increased ovulation rate, but not litter size at d 30 postmating. There was no beneficial effect of Regu-mate pretreatment on the response to P.G. 600 in prepubertal gilts. PMID- 11768103 TI - Biological and economic performance of early-weaned Angus steers. AB - Over 2 yr, 45 Angus-sired steer offspring of Angus and Angus crossbred females were used to determine the effects of early weaning on feedlot performance, carcass characteristics, and economic return to the cow-calf enterprise. Steers were assigned by birth date to one of two weaning treatments: 1) weaned at an average age of 100 d (early weaned) or 2) weaned at an average age of 200 d (normally weaned). Within 36 d of weaning, steers were given ad libitum access to a high-concentrate diet (90% dry, wholeshelled corn). Steers were harvested when 12th-rib fat thickness averaged 1.27 cm within treatment as estimated by ultrasound. Carcass measurements were taken 48 h postmortem and rib steak tenderness was determined at 14 d postmortem by Warner-Bratzler shear force. Early-weaned steers had greater ADG from time of early weaning to normal weaning than suckling normally weaned steers (1.27 vs. 0.86 kg/d, respectively; P < 0.001). However, early-weaned steers tended to have lower ADG for the entire finishing period than did normally weaned steers (1.33 vs. 1.39 kg/d, respectively; P = 0.08). Compared with normally weaned steers, early-weaned steers had lower daily DMI (7.40 vs. 5.95 kg/d, respectively; P < 0.001) and lower total DMI for the finishing period (1,618 vs 1,537 kg, respectively; P < 0.05). Early-weaned steers had greater gain:feed for the finishing period than normally weaned steers (0.223 vs 0.189, respectively; P < 0.001). Carcass weights were lighter for early-weaned steers than for normally weaned steers (277.9 vs. 311.2 kg, respectively; P < 0.001). There was no difference in yield grade (3.1 vs. 3.2; P < 0.10) between treatments. All carcasses graded Low-Choice or greater, and there was no difference in the percentage of carcasses grading Mid Choice or greater (94.5 vs 83.9% for early- and normally-weaned, respectively; P > 0.10). Warner-Bratzler shear force values were similar between treatments. Early-weaned steers had a lower cost of gain than normally weaned steers ($ 0.82 vs. 0.91/kg, respectively; P < 0.001). However, due to lighter carcass weights, early-weaned steers generated less return to the cow-calf enterprise than normally weaned steers ($ 380.89 vs 480.08/steer; P < 0.001). The early weaning of steers at 100 d of age decreased total DMI, improved gain:feed, and lowered the cost of gain; however, return to the cow-calf enterprise was decreased due to lighter carcass weights. PMID- 11768104 TI - Effect of nipple drinker water flow rate and season on performance of lactating swine. AB - A cooperative study involving six experiment stations and 236 crossbred litters was conducted to determine the effect of nominal nipple drinker water flows of 700 mL/min and 70 mL/min (actual = 701 and 76 mL/min, respectively) during winter (November through February; 124 litters) and summer (June through August; 112 litters) seasons on performance of lactating sows and their litters. Within a season, sows were paired according to expected farrowing date and assigned at random to crates. Water flow rate treatments were assigned at random to sows within pairs. Sows were housed in farrowing crates from d 109 of gestation until either d 21 (two stations) or d 28 of lactation (four stations). Within 24 h after farrowing, litters were adjusted to contain 8 to 12 piglets. Sow feed intake (SFI) and litter weight (LW) were recorded weekly. Sow weights were recorded at d 109 of gestation, d 0, and d 21 of lactation. Sows lactating beyond 21 d were also weighed on d 28. Analysis of covariance was applied to sow weight change, average daily SFI, and LW data where litter size after crossfostering was the covariate. Average ambient temperature 30 cm above the floor at 0830 and 1600 was 24.6 +/- 0.15 degrees C and 29.4 +/- 0.14 degrees C, respectively, during summer and 20.7 +/-0.13 degrees C and 21.8 +/- 0.11 degrees C during winter trials. Restricted drinker water flow rate decreased SFI (P < 0.01; 4.59 vs. 3.94 kg/d, respectively, for 700 and 70 mL/min) and increased BW loss (P < 0.01; 0.56 vs 0.89 kg/d, respectively for 700 and 70 mL/min) but did not affect litter size (P > 0.87) or LW (P > 0.89) during the first 21 d of lactation. During d 22 to 28, the 70 mL/min flow decreased SFI (P < 0.01; 5.02 vs. 4.47 kg/d respectively, for 700 and 70 mL/min). Over the 21-d lactation period, the 70 mL/min treatment depressed (P < 0.01) SFI more during the winter (5.12 vs. 4.24 kg/d for 700 and 70 mL/ min, respectively) than during the summer (4.05 vs 3.65 kg/d for 700 and 70 mL/min, respectively). Season affected SFI (P < 0.01; 4.68 vs. 3.85 kg/d, respectively, for winter and summer), sow weight loss (P < 0.001; 0.46 vs 0.83 kg/d, respectively, for winter and summer), and LW at 21 d (P < 0.05; 52.8 vs. 49.6 kg, respectively, for winter and summer) but not (P > 0.96) the number of pigs per litter. Results of this study suggest that ample access to drinking water and controlling ambient temperature during summer months are essential for sow and litter performance. PMID- 11768105 TI - Estimates of covariance functions for growth from birth to 630 days of age in Nelore cattle. AB - Weight records of Brazilian Nelore cattle, from birth to 630 d of age, recorded every 3 mo, were analyzed using random regression models. Independent variables were Legendre polynomials of age at recording. The model of analysis included contemporary groups as fixed effects and age of dam as a linear and quadratic covariable. Mean trends were modeled through a cubic regression on orthogonal polynomials of age. Up to four sets of random regression coefficients were fitted for animals' direct and maternal, additive genetic, and permanent environmental effects. Changes in measurement error variances with age were modeled through a variance function. Orders of polynomial fit from three to six were considered, resulting in up to 77 parameters to be estimated. Models fitting random regressions modeled the pattern of variances in the data adequately, with estimates similar to those from corresponding univariate analysis. Direct heritability estimates decreased after birth and tended to be lowest at ages at which maternal effect estimates tended to be highest. Maternal heritability estimates increased after birth to a peak around 110 to 120 d of age and decreased thereafter. Additive genetic direct correlation estimates between weights at standard ages (birth, weaning, yearling, and final weight) were moderate to high and maternal genetic and environmental correlations were consistently high. PMID- 11768106 TI - Genetic correlation estimates between ultrasound measurements on yearling bulls and carcass measurements on finished steers. AB - Carcass and growth measurements of finished crossbred steers (n = 843) and yearling ultrasound and growth measurements of purebred bulls (n = 5,654) of 11 breeds were analyzed to estimate genetic parameters. Multiple-trait restricted maximum likelihood (REML) was used to estimate heritabilities and genetic correlations between finished steer carcass measurements and yearling bull ultrasound measurements. Separate analyses were conducted to examine the effect of adjustment to three different end points: age, backfat thickness, and weight at measurement. Age-constant heritability estimates from finished steer measurements of hot carcass weight, carcass longissimus muscle area, carcass marbling score, carcass backfat, and average daily feedlot gain were 0.47, 0.45, 0.35, 0.41, and 0.30, respectively. Age-constant heritability estimates from yearling bull measurements of ultrasound longissimus muscle area, ultrasound percentage of intramuscular fat, ultrasound backfat, and average daily postweaning gain were 0.48, 0.23, 0.52, and 0.46, respectively. Similar estimates were found for backfat and weight-constant traits. Age-constant genetic correlation estimates between steer carcass longissimus muscle area and bull ultrasound longissimus muscle area, steer carcass backfat and bull ultrasound backfat, steer carcass marbling and bull ultrasound intramuscular fat, and steer average daily gain and bull average daily gain were 0.66, 0.88, 0.80, and 0.72, respectively. The strong, positive genetic correlation estimates between bull ultrasound measurements and corresponding steer carcass measurements suggest that genetic improvement for steer carcass traits can be achieved by using yearling bull ultrasound measurements as selection criteria. PMID- 11768107 TI - Intramuscular fat content and genetic variants at fatty acid-binding protein loci in Austrian pigs. AB - Intramuscular fat is an important meat quality trait in pig production. Previously, genetic variants of the heart fatty acid-binding protein (H-FABP) gene and the adipocyte fatty acid-binding protein (A-FABP) gene were suggested to be associated with intramuscular fat content. The objective of this investigation was to study these associations in the three most important Austrian breeding populations (Pietrain, Large White, and Landrace). Restriction fragment length polymorphism analysis of the H-FABP gene revealed a new MspI polymorphic site and genetic variation in all three breeds. Microsatellite analysis of the A-FABP locus showed up to nine different microsatellite alleles segregating. In Austrian breeds, no significant influence of the A-FABP and H-FABP gene polymorphisms on intramuscular fat could be detected. We also evaluated possible associations between the genetic variations at the H-FABP and A-FABP loci and other growth and carcass traits (average daily gain, feed conversion ratio, lean meat content, pH values, meat color, and drip loss). With regard to the extent of the effects, these genetic markers cannot be recommended for selection on growth and carcass traits in Austrian breeding populations. PMID- 11768108 TI - Genetic and phenotypic variance and covariance components for feed intake, feed efficiency, and other postweaning traits in Angus cattle. AB - Records on 1,180 young Angus bulls and heifers involved in performance tests were used to estimate genetic and phenotypic parameters for feed intake, feed efficiency, and other postweaning traits. The mean age was 268 d at the start of the performance test, which comprised 21-d adjustment and 70-d test periods. Traits studied included 200-d weight, 400-d weight, scrotal circumference, ultrasonic measurements of rib and rump fat depths and longissimus muscle area, ADG, metabolic weight, daily feed intake, feed conversion ratio, and residual feed intake. For all traits except the last five, additional data from the Angus Society ofAustralia pedigree and performance database were included, which increased the number of animals to 27,229. Genetic (co)variances were estimated by REML using animal models. Direct heritability estimates for 200-d weight, 400 d weight, rib fat depth, ADG, feed conversion,and residual feed intake were 0.17 +/- 0.03, 0.27 +/- 0.03, 0.35 +/- 0.04, 0.28 +/- 0.04, 0.29 +/- 0.04, and 0.39 +/ 0.03, respectively. Feed conversion ratio was genetically (r(g) = 0.66 ) and phenotypically (r(p) = 0.53) correlated with residual feed intake. Feed conversion ratio was correlated (r(g) = -0.62, r(p) = -0.74) with ADG, whereas residual feed intake was not (rg = -0.04, r(p) = -0.06). Genetically, both residual feed intake and feed conversion ratio were negatively correlated with direct effects of 200-d weight (r(g) = -0.45 and -0.21) and 400-d weight (r(g) = 0.26 and -0.09). The correlations between the remaining traits and the feed efficiency traits were near zero, except between feed intake and feed conversion ratio (r(g) = 0.31, r(p) = 0.23), feed intake and residual feed intake (r(g) = 0.69, r(p) = 0.72), and rib fat depth and residual feed intake (r(g) = 0.17, r(p) = 0.14). These results indicate that genetic improvement in feed efficiency can be achieved through selection and, in general, correlated responses in growth and the other postweaning traits will be minimal. PMID- 11768109 TI - Detection and characterization of quantitative trait loci for meat quality traits in pigs. AB - In an experimental cross between Meishan and Dutch Large White and Landrace lines, 785 F2 animals with carcass information and their parents were typed for molecular markers covering the entire porcine genome. Linkage was studied between these markers and eight meat quality traits. Quantitative trait locus analyses were performed using interval mapping by regression under two genetic models: 1) the line-cross approach, where the founder lines were assumed to be fixed for different QTL alleles and 2) a half-sib model where a unique allele substitution effect was fitted within each of the 38 half-sib families. The line-cross approach included tests for genomic imprinting and sex-specific QTL effects. In total, three genome-wide significant and 26 suggestive QTL were detected. The significant QTL on chromosomes 3, 4, and 13, affecting meat color, were only detected under the half-sib model. Failure of the line-cross approach to detect the meat color QTL suggests that the founder lines have similar allele frequencies for these QTL. This study provides information on new QTL affecting meat quality traits. It also shows the benefit of analyzing experimental data under different genetic and statistical models. PMID- 11768110 TI - Effects of growth factors on insulin-like growth factor binding protein (IGFBP) secretion by primary porcine satellite cell cultures. AB - Insulin-like growth factor-binding proteins (IGFBP) regulate the biological functions of insulin-like growth factors (IGF) and may affect cell growth through IGF-independent actions. Growth factors and hormones have been shown to alter IGFBP production by target cells suggesting that the effects of these factors may be partially mediated by the local production of IGFBP. Growth factors, including IGF-I, transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) have potent effects on satellite cell proliferation and differentiation, and some of these factors have been shown to alter IGFBP production in various cell types. Consequently, some of their actions on muscle satellite cells may be mediated by the local production of IGFBP. In this study, we measured the effects of IGF-I, bFGF, and TGF-beta1 on IGFBP production by primary porcine satellite cell (PSC) cultures after first determining physiologically active concentrations of these growth factors to use according to [3H]thymidine incorporation dose responses. There is little information on the effects of these growth factors on IGFBP production in primary porcine myogenic cells due to the confounding affects of contaminating nonmuscle fibroblasts. Comparative studies show that primary porcine satellite cells produce IGFBP-3 and -5 whereas porcine muscle-derived nonfusing cells (FIB) produce IGFBP-2 and -4 but not IGFBP-3 or -5. Because of this, our investigations have focused on growth factor-induced production of IGFBP-3 and -5 in primary porcine satellite cells cultures. Both IGF-I and bFGF exhibited dose-dependent increases in [3H]thymidine incorporation with increasing concentration from 1 to 50 ng/mL (P < 0.05), whereas TGF-beta1 caused a dose-dependent decrease from 0.01 to 0.5 ng/mL (P < 0.05). When 20 ng/ mL of IGF-I was added to the media, IGFBP-3 was increased approximately 65% (P < 0.05) and IGFBP-5 was increased approximately twofold (P < 0.05). The addition of 0.5 ng/mL TGF-beta1 caused more than a two-fold increase in IGFBP-3 (P < 0.05) and approximately an 80% increase in IGFBP-5 (P < 0.05), whereas 50 ng/ mL of bFGF caused approximately 40% (P < 0.05) and 70% (P < 0.05) increases in IGFBP-3 and -5, respectively. Neither IGFBP-3 nor -5 was detectable in the conditioned media from fibroblasts whether or not IGF-I, TGF- beta1 or bFGF were present. These data suggest that the effects of IGF-I, TGF- beta1 and bFGF on porcine satellite cells may in part be through the autocrine/ paracrine production of IGFBP-3 and -5 by porcine satellite cells. PMID- 11768111 TI - Effects of dietary supplementation with vitamin E and organic selenium on the oxidative stability of beef. AB - The effects of supplementation of beef cattle diets with organic Se (0.3 mg/kg) and vitamin E (300 I.U. alpha-tocopheryl acetate/kg feed), for 55 d preceding slaughter, on the antioxidant status and oxidative stability of muscle was examined. Dietary vitamin E supplementation led to an increase (P < 0.05) in plasma, and longissimus muscle alpha-tocopherol levels. In minced longissimus muscle stored in 80% 02:20% CO2, lipid and oxymyoglobin oxidation were lower (P < 0.05) in muscle from vitamin E-supplemented animals compared with unsupplemented animals. Dietary Se supplementation did not significantly affect muscle Se levels, glutathione peroxidase activity, or susceptibility to lipid and oxymyoglobin oxidation in the presence or absence of vitamin E. Covariance analysis indicated that, in addition to muscle alpha-tocopherol, differences in muscle glutathione peroxidase activity, and pH could account for variation in the susceptibility of muscle to lipid and oxymyoglobin oxidation. PMID- 11768112 TI - Relationships between behavioral and meat quality characteristics of pigs raised under barren and enriched housing conditions. AB - In this study the effects of barren vs enriched housing conditions of pigs on their behavior during the lairage period (2-h holding period before slaughter), carcass characteristics, postmortem muscle metabolism, and meat quality were studied. The barren housing system was defined by common intensive housing conditions (i.e., with slatted floors and recommended space allowances), whereas the enriched environment incorporated extra space and straw for manipulation. Salivary cortisol concentrations were measured before transport and at the end of the lairage period. During the lairage period the percentage of time spent walking and fighting by the pigs was registered. Carcass characteristics such as weight, meat percentage, and backfat thickness were determined. At 5 min, 45 min, 4 h, and 24 h postmortem, pH, temperature, and lactate concentrations were determined in the longissimus lumborum (LL) and biceps femoris (BF) muscles. Capillarization of the muscle, mean muscle fiber area, and color and drip loss after 2 and 5 d of storage were determined for both muscle types. Pigs from the barren environment had a significantly higher increase in cortisol from farm to slaughter, but no differences in behavior were observed during the lairage period. Carcass characteristics did not differ between pigs from barren and those from enriched housing conditions. Postmortem lactate formation was significantly lower in LL muscles of enriched pigs at 4 and 24 h postmortem. Capillary density and mean muscle fiber area did not differ between the groups of pigs. The percentage of drip loss at 2 and 5 d after storage of LL muscle samples from enriched-housed pigs was significantly lower than that of the barren-housed pigs. Similar tendencies were found for the BF muscle from pigs kept in an enriched environment, but these were not statistically significant. The housing system did not affect meat color. It is concluded that on-farm improvement of animal welfare by environmental enrichment can also lead to beneficial economic effects after slaughter by improving the water-holding capacity of pork. PMID- 11768113 TI - Effects of supplemental vitamin D3 on feed intake, carcass characteristics, tenderness, and muscle properties of beef steers. AB - Research was conducted to determine the effects of supplemental dietary vitamin D3 on DMI, carcass traits, Warner Bratzler shear (WBS) force, calpastatin activity, plasma minerals, pH (0, 3, 12, and 24 h after slaughter), water-holding capacity (WHC), and sensory characteristics of three muscles. Pre-slaughter vitamin D3 treatments included no supplemental vitamin D3, 6 x 106 IU (MIU) of vitamin D3 for 4 d, or 6 MIU of vitamin D3 for 6 d. Cattle were slaughtered and carcasses were chilled for 48 h before removal of steaks from the longissimus, gluteus medius, and biceps femoris muscles. Steaks were aged at 2 degrees C for 7, 14, or 21 d before cooking to a final internal temperature of 70 degrees C for WBS and sensory panel analysis. Dry matter intake was lower for steers supplemented with vitamin D3 for 4 or 6 d. Live and carcass weights were lower (P < 0.05) in steers supplemented with vitamin D3. Supplementing 6 MIU/6 d of vitamin D3 decreased (P < 0.05) WBS values of gluteus steaks (pooled over aging times). Longissimus steaks from steers supplemented with vitamin D3 for 6 d had lower (P < 0.05) WBS force values than these steaks from control steers or steers fed vitamin D3 for 4 d at 7 d postmortem. Biceps femoris steaks from steers receiving vitamin D3 for 4 d had higher WBS values than steaks from control steers at 14 and 21 d postmortem. Feeding vitamin D3 at 6 MIU for 6 d decreased (P < 0.05) the percentage of steaks that had WBS values > or = 3.86 kg for all steaks. Feeding vitamin D3 had no effect on palatability traits evaluated by trained panelists. Blood Ca concentrations were greater (P < 0.05) when vitamin D3 was fed and with increased vitamin D3 feeding time. Feeding vitamin D3 for 6 d (vs 4 d) delayed pH decline for all muscle types after 0, 3, and 12 h postmortem. Water-holding capacity was increased (P > 0.02) after 0 h, 24 h, and 21 d postmortem when vitamin D3 was fed and was greater at 0 and 24 h if vitamin D3 was fed for 6 d rather than 4 d. These data suggest that supplementing 6 MIU of vitamin D3 will decrease DMI and improve beef tenderness through increased blood plasma Ca concentrations and WHC. PMID- 11768114 TI - Computer image analysis for prediction of carcass composition from cross-sections of Japanese Black steers. AB - Carcasses from Japanese Black steers were used to obtain prediction equations for carcass composition from information derived by computer image analysis of carcass cross-section images. The total weights of lean, fat, and bone were obtained from the left sides of 55 carcasses (Data Set I) and 18 carcasses (Data Set II) by physical dissection. The information such as total lean, fat, and bone areas in the cross-sections; muscle area, muscle circumference, short and long radius axis lengths, and direction of long radius axis; and geometric distance between any two muscle centers of gravity was obtained by scanning and image analysis of pictures of the cross-sections of the beef side at the 6th/7th rib interface. The coefficients of determination of the multiple regression equations estimated from Data Set I for kilograms of lean, fat, and bone were 0.76, 0.82, and 0.69, respectively, whereas for the percentages of lean, fat, and bone they were 0.57, 0.66, and 0.42, respectively. The multiple regression equations from Data Set I was applied to Data Set II in order to test the applicability of the prediction equations obtained. The correlation coefficients between the value predicted by the multiple regression equation and the measurement obtained by physical dissection for kilograms of lean, fat, and bone were 0.71, 0.72, and 0.70, respectively, whereas those for the percentages of lean, fat, and bone were 0.63, 0.44, and 0.29, respectively. The results indicate that the information obtained from the carcass cross-sections by the computer image analysis method can be used to predict carcass composition in Japanese Black steers. PMID- 11768115 TI - Effect of dietary protein source and lysine:DE ratio on growth performance, meat quality, and body composition of growing-finishing pigs. AB - The effects of four protein sources (soybean meal, sunflower meal, pea, and fish meal as the main protein source) and three apparent ileally digestible Lys:DE ratios (0.50, 0.43, 0.36 and 0.42, 0.36, 0.30 g Lys/MJ DE for 30 to 60 kg BW and 60 to 105 kg BW, respectively) in pig diets on growing-finishing performance, and carcass and meat quality traits were investigated. Eight individually housed animals per treatment received the diets from 30 to 105 kg BW at a level of 3.0 times maintenance requirements of energy. The ileal digestibility of protein sources was determined in a previous digestibility experiment. Protein sources showed no differences in growth performance from 30 to 105 kg BW. From 30 to 60 kg BW soybean treatment had lowest performance. The protein sources had no effect on lean meat percentage, liver weight, or meat quality (intramuscular fat content, pH at 45 min and 24 h after slaughter, drip loss, and meat color measured 24 h and 4 d after slaughter). The experimental diets formulated on the basis of similar apparent ileal digestible lysine content resulted in similar body composition regardless of the protein source used (P > 0.05). Reducing the Lys:DE ratio from 0.50/0.43 to 0.36/0.30 (by about 28%) reduced BW gain by 119 g/d from 30 to 60 kg and by 151 g/d from 60 to 105 kg BW. The gain:feed ratio increased by 82 g/kg in the first phase and by 47 g/kg in the second phase for the highest Lys:DE treatment compared with the lowest. Reducing Lys:DE ratio did not modify meat quality traits. A high Lys:DE ratio was associated with a high lean meat percentage. Differences between the medium- and low-Lys:DE groups were not significant. Lowering the Lys:DE ratio increased (P < 0.05) crude fat and fatty tissue content and decreased (P < 0.05) protein and muscle content in the body. Ash content and bone volume were not affected by Lys:DE ratio (P > 0.05). The chemical composition of the carcass can be predicted with moderate accuracy (R2 = 0.39 to 0.58) using volumetric composition data of previously frozen carcasses. In conclusion, similar growth performance, carcass and meat quality, and body composition can be expected if diet formulation is based on the apparent ileally digestible amino acid contents of feedstuffs, independent of dietary protein sources. Diminishing Lys:DE ratios reduce growth performance but do not modify meat quality traits. The chemical composition of the carcass can be predicted with moderate accuracy using the volumetric composition of thawed carcasses. PMID- 11768116 TI - Effects of conjugated linoleic acid on the belly firmness and fatty acid composition of genetically lean pigs. AB - A study of the effects of conjugated linoleic acid (CLA) on the belly firmness and fatty acid composition of genetically lean pigs was conducted. From 75 to 120 kg live weight, 30 gilts were allowed ad libitum access to a corn-soybean meal diet supplemented with either 1% CLA oil (CLA-60) or 1% sunflower oil (SFO) or were fed the sunflower oil-supplemented diet restricted to the amount consumed by pigs fed the CLA-60 diet (RSFO). Conjugated linoleic acid oil consists of 60% positional and geometric isomers of CLA. Pigs fed SFO exhibited higher average daily gains (0.98 vs 0.80 kg/d, P < 0.01) than RSFO-fed pigs, but there were no effects of dietary treatment on feed intake or feed efficiency. Dietary treatment did not affect (P > 0.05) backfat thickness or longissimus muscle area. Bellies of gilts fed CLA-60 were subjectively evaluated to be firmer (2.91 vs 2.43 or 2.07 +/- 0.13, P < 0.01) than those of SFO- or RSFO-fed gilts, respectively. The longissimus muscle of gilts fed CLA-60 contained more saturated fatty acids (39.77 vs. 36.04 or 36.73 +/- 0.74%, P < 0.001) and less unsaturated fatty acids (60.23 vs 63.96 or 63.27 +/- 0.74%, P < 0.001) than that of gilts fed SFO or RSFO, respectively. The belly fat of gilts fed CLA-60 contained more saturated fatty acids (44.45 vs. 37.50 or 36.60 +/- 0.46%, P < 0.001) and less unsaturated fatty acids (54.78 vs. 61.75 or 62.47 +/- 0.46%, P < 0.001), resulting in lower iodine values (57.69 vs 66.37 or 65.62 +/- 0.91, P < 0.001) than that of gilts fed SFO or RSFO, respectively. Gilts fed CLA-60 accumulated more CLA in the longissimus muscle (0.55 vs 0.09 or 0.09 +/- 0.03%, P < 0.01) and belly fat (1.56 vs. 0.13 or 0.13 +/- 0.15%, P < 0.001) than did gilts fed SFO or RSFO, respectively. Dietary treatment did not affect (P > 0.05) 24-h pH, drip loss or subjective quality evaluations of the longissimus muscle. The effect of supplemental CLA to improve belly firmness is of practical significance and may provide a nutritional solution to carcass fat and belly firmness problems, thereby enhancing the overall value of extremely lean carcasses. PMID- 11768117 TI - Low-phytic acid corn improves nutrient utilization for growing pigs. AB - Thirty-five crossbred barrows averaging 14.5 kg initial BW were used in a 5-wk experiment to compare the P availability and nutritional value of a low-phytate hybrid corn (LPC, 0.26% total P, 0.08% phytic acid P) homozygous for the lpa 1-1 allele with a nearly isogenic normal hybrid corn (NC, 0.25% total P, 0.20% phytic acid P). The pigs were fed individually twice daily in metabolism pens. Three semipurified diets were created in which corn was the only source of phytate. Diet 1 contained 72% NC, 0.15% estimated available P (aP) and 0.55% Ca. Diet 2 contained 72% LPC, 0.24% aP, and 0.55% Ca. The only differences between Diets 1 and 2 were the source of corn and the levels of aP. No inorganic P (iP) was added to these diets in order to measure the animal response to the different levels of aP in the corn hybrids. Diet 3 was NC Diet 1 supplemented with iP to equal the level of aP in LPC Diet 2. Diets 4 and 5 were practical corn-soybean meal diets formulated with each corn to meet all minimum nutrient requirements and contained 0.30% aP and 0.65% Ca. For the semipurified diets, pigs fed LPC Diet 2 had higher (P < 0.01) growth performance, bone breaking strength, P absorption and retention, Ca absorption and retention, and N retention than pigs fed NC Diet 1. However, when the NC diet was supplemented with iP to equal the aP in the LPC diet, most criteria were similar (P > or = 0.2), indicating an equal nutritional value for both corn hybrids after adjusting for phytate level. The only treatment difference, other than P excretion, between the practical corn diets supplemented with soybean meal was a higher (P < 0.05) bone breaking strength for pigs fed LPC Diet 5 compared with NC Diet 4. The use of LPC in pig diets reduced P excretion in swine waste by 50 and 18.4% in the semipurified and practical diets, respectively, compared with NC. Using our in vitro procedure designed to simulate the digestive system of the pig, the availability of P for pigs was estimated at 56% for LPC and 11% for NC. PMID- 11768119 TI - Nocturnal melatonin and prolactin plasma concentrations in sheep selected for fertility in autumn lambing'. AB - Ewes selected for fertility in autumn lambing were used to evaluate correlated responses in nocturnal hormone levels. Four jugular blood samples were obtained during nighttime in August from each of 113 selected and 69 control ewes. Melatonin levels were lower for selected ewes (143 +/- 14 pg/mL) than for control ewes (184 +/- 13 pg/mL), and melatonin levels decreased with increases in estimated breeding values (EBV) for fertility (-2.23 +/- 0.79 pg mL(-1) x %(-1)). Prolactin levels were higher for selected ewes (90 +/- 7 ng/mL) than for control ewes (52 +/- 7 ng/mL), but significant line x ewe age interaction was also observed, with smaller differences in prolactin levels in 2-yr-old and older ewes (74 +/- 7 vs. 56 +/- 9 ng/mL for select and control ewes, respectively; P < 0.20 before and P = 0.05 after logarithmic transformation). Prolactin levels increased with both fertility EBV (1.23 +/- 0.53 ng mL(-1) x %(-1)) and maternal birth weight EBV (9.0 +/- 4.0 ng x ml(-1) kg(-1)). Heritability estimates were 0.43 (P < 0.02) for melatonin levels and 0.11 (P > 0.25) for prolactin levels. Thus, we conclude that selection for fertility in autumn lambing has affected patterns of melatonin and prolactin secretion during the dark phase. PMID- 11768118 TI - Effect of human chorionic gonadotropin on luteal function and reproductive performance of high-producing lactating Holstein dairy cows. AB - The objectives were to evaluate effects of human chorionic gonadotropin (hCG) (3,300 IU i.m.) administered on d 5 after AI on CL number, plasma progesterone concentration, conception rate, and pregnancy loss in high-producing dairy cows. Following the synchronization of estrus and AI, 406 cows were injected with either hCG or saline on d 5 after AI in a randomized complete block design. Blood sampling and ovarian ultrasonography were conducted once between d 11 and 16 after AI. Pregnancy diagnoses were performed on d 28 by ultrasonography and on d 45 and 90 after AI by rectal palpation. Treatment with hCG on d 5 resulted in 86.2% of the cows with more than one CL compared with 23.2% in controls. Plasma progesterone concentrations were increased by 5.0 ng/mL in hCG-treated cows. The presence of more than one CL increased progesterone concentration in hCG-treated cows but not in controls. Conception rates were higher for hCG-treated cows on d 28 (45.8 > 38.7%), 45 (40.4 > 36.3%), and 90 (38.4 > 31.9%) after AI. Treatment with hCG improved conception rate in cows losing body condition between AI and d 28 after Al. Pregnancy losses were similar between treatment groups. Treatment with hCG on d 5 after AI induces accessory CL, enhances plasma progesterone concentration, and improves conception rate of high-producing dairy cows. PMID- 11768120 TI - LHRH antagonist decreases LH and progesterone secretion but does not alter length of estrous cycle in heifers. AB - The objective of this study was to evaluate the suppressive effect of an LHRH antagonist, Cetrorelix SB-75 (SB-75), on secretion of LH, FSH and ovarian function in beef heifers. In Exp. 1, heifers were treated with a single dose of 10 microg/kg body weight intramuscularly on d 3 of the estrous cycle. In Exp. 2, heifers received either a single injection (100 microg/kg) of SB-75 on d 3 of the estrous cycle or multiple injections of 20 microg/kg on d 3, 4, 5, 6, and 7. Serum LH, but not FSH, was suppressed from one to several days. However, neither FSH nor progesterone was significantly altered. In Exp. 3, heifers received an injection vehicle (5% mannitol) or 100 microg/kg BW of SB-75 on d 1 of the estrous cycle (30 h after first observed standing estrus). Injection of SB-75 suppressed LH pulse frequency on d 3, 5, and 7 (P < 0.001). The mean LH concentrations in the SB-75 treatment groups were lower on d 3 (P < 0.01) and 5 (P < 0.05). There were no differences (P > 0.1) between the two groups in the mean concentrations of LH on d 1, 7, or 14. Treatment did not affect the secretion pattern or concentration of FSH. Injection of SB-75 did not alter estradiol-173 concentrations (P > 0.1). Treatment reduced corpus luteum (CL) function as indicated by lower progesterone production. However, the length of the estrous cycle was not shortened. These data show that the CL can form and survive in the face of depressed LH concentrations during the early stages of the estrous cycle. PMID- 11768121 TI - Effect of feeding frequency on bacterial and fungal concentrations, pH, and other parameters in the rumen. AB - Three sheep were fed a pelleted high-roughage diet either once, 6, or 24 times per day in a 3 x 3 Latin square trial. During each 21-d period, 14 d were allowed for adaptation followed by a 7-d collection period, in which samples for microbial counts were taken on d 1 and 5 and several rumen parameters were measured on d 2 and 6. Bacterial concentrations were not different between feeding frequencies on the first sampling day but were higher (P < 0.05) on the second sampling day when the sheep were fed 24 times a day. Fungal concentrations were not different among feeding frequencies on either sampling day. No effects of feeding frequency were observed for the concentration of cellulolytic bacteria or fungi. On d 2, ruminal volume was larger (P < 0.05) with six feedings than with one feeding and fluid volume turnover was greater (P < 0.05) when sheep were fed 24 times per day. Rumen pH values were higher (P < 0.01) on both d 1 and 5 when the sheep were fed once a day and the percentage of rumen dry matter was highest (P < 0.02) with 24 feedings. These findings would suggest that if the same amount of a given diet is fed daily, the number of feedings does not markedly affect microbial concentrations, rumen volume, or liquid turnover time. PMID- 11768122 TI - Effects of bovine somatotropin and thyroid hormone status on hormone levels, body weight gain, and mohair fiber growth of Angora goats. AB - Forty-eight Angora goats (24 wethers and 24 doelings; 5 mo old; 16 +/- 0.5 kg initial BW) were used in an experiment with a 2 x 3 factorial treatment arrangement (n = 8) to evaluate effects of recombinant bovine somatotropin (bST) administration and thyroid hormone status (euthyroid, hypothyroid, and hyperthyroid) on hormone levels, ADG, and mohair fiber growth. The bST was a slow release zinc-based suspension, with sustained delivery (100 microg/[kg BW x d]) over a 14-d period. Hyperthyroidism was maintained by daily treatment with thyroxine (T4; 150 microg/[kg BW x d]), and hypothyroidism was achieved by feeding 6 mg/(kg BW x d) of propylthiouracil. The experiment was conducted in July to September and consisted of a 2-wk pretreatment period and 8 wk of bST treatment. Goats were given ad libitum access to a diet with 15% CP and 2.54 Mcal/ kg ME (DM basis). Concentrations of T4 and T3 were greatest (P < 0.01) among treatments for hyperthyroid-bST and hyperthyroid-control (T4: 38.6 and 38.0 microg/dL; T3: 406 and 385 ng/dL, respectively); similar among euthyroid-control, euthyroid-bST, and hypothyroid-bST (T4: 11.1, 11.5, and 9.8 microg/dL, respectively; T3: 232, 252, and 226 ng/dL, respectively); and lowest (P < 0.01) for hypothyroid-control (T4: 5.1 microg/dL; T3: 144 ng/dL). Plasma concentration of insulin-like growth factor-I was greatest (P < 0.01) for euthyroid-bST (596 ng/mL) and hypothyroid-bST (618 ng/mL); however, concentration for hyperthyroid bST was similar to those for euthyroid-control, hypothyroid-control, and hyperthyroid-control (188, 178, 187, and 191 ng/mL, respectively). Dry matter intake was greatest (P < 0.05) for euthyroid-bST (794 g/d), similar among hypothyroid treatments (693 and 703 g/d for control and bST, respectively) and euthyroid-control (681 g/d), and lowest for hyperthyroid groups (554 and 518 g/d for control and bST, respectively); ADG for hyperthyroid goats (11 g/d) was lower than with hypothyroidism and euthyroidism (72 and 73 g/d, respectively); and mohair fiber growth was greater (P < 0.01) for hyperthyroidism (0.133 g/[100 cm2 x d]) than for hypothyroid and euthyroid goats (0.102 and 0.104 g/[100 cm2 x d], respectively). Hyperthyroidism also increased mohair length growth rate by 15% and decreased fiber diameter by 7.8% (P < 0.01). These results demonstrate interactions between growth hormone administration and thyroid hormone status, although these influences had limited effects on ADG and mohair fiber growth. PMID- 11768123 TI - Performance, carcass characteristics, and lipid metabolism in growing and finishing Simmental steers fed varying concentrations of copper. AB - An experiment was conducted to determine the effects of dietary copper (Cu) on performance, carcass characteristics, and lipid metabolism in Simmental steers. Thirty-six Simmental steers (329.3 +/-11.4 kg) were stratified by weight and randomly assigned to treatments. Treatments consisted of the following: control (no supplemental Cu) and 10 or 40 mg Cu/kg DM from Cu sulfate. Each treatment consisted of six replicate pens, with each pen containing two steers. A corn silage-soybean meal-based diet was fed for 56 d. Steers were then switched to a high concentrate diet. Performance was not affected by treatment during the growing or finishing phases. Plasma Cu concentrations were higher (P < 0.05) in steers receiving supplemental Cu by d 56 of the growing phase and remained higher (P < 0.05) at all 28-d sampling periods during the finishing phase. Liver Cu concentrations were higher (P < 0.001) in steers receiving supplemental Cu at the end of the growing phase and on d 84 and at the end of the finishing phase. Steers supplemented with 40 mg Cu had higher (P < 0.001) liver Cu concentrations than those supplemented with 10 mg Cu/kg DM. Serum and longissimus muscle cholesterol concentrations were similar between treatments. Longissimus muscle and backfat fatty acid composition was similar between treatments. These results indicate that Cu supplementation given to Simmental steers increased Cu status but had no effect on performance, carcass characteristics, or lipid or cholesterol metabolism. PMID- 11768124 TI - Effects of supplementing combinations of inorganic and complexed copper on performance and liver mineral status of beef heifers consuming antagonists. AB - Performance, immune response, and liver trace mineral status were measured in growing heifers supplemented with different copper (Cu) concentrations and sources when diets contained the Cu antagonists Mo, S, and Fe. Sixty Angus x Hereford heifers were managed in two groups for 112 d and were either individually fed diets and mineral treatments using individual feeding stalls (Stall) or pen-fed grass hay and individually supplemented mineral treatments (Pen). The basal diet of grass hay, rolled barley, and soybean meal was analyzed to contain 6 mg Cu/kg DM. The treatments consisted of 1) no supplemental Cu (Control); 2) 49 mg Cu/kg DM from Cu sulfate (i.e. approximately five times NRC recommendation for Cu from CuSO4) (5X-SO4); 3). 22 mg Cu/kg DM from CuSO4 (2X SO4); 4). 22 mg Cu/kg DM from a combination of 50% CuSO4 and 50% Cu-amino acid complex (50-50); and 5). 22 mg Cu/kg DM from a combination of 25% CuSO4, 50% Cu amino acid complex, and 25% Cu oxide (CuG) (25-50-25). All heifers were supplemented with the Cu antagonists Mo (10 mg/kg DM), S (2,900 mg/kg DM), and Fe (500 mg/kg DM). These diets resulted in dietary Cu:Mo ratios that averaged 0.5:1 for Control, 4.5:1 for the 5X-SO4, and 2.4:1 for 2X-SO4, 50-50, and 25-50-25. Rate and efficiencies of gain and cell-mediated immune function were not different (P > 0.10) among treatments. Data suggest supplements containing combinations of inorganic and complexed Cu interacted differently in the presence of Mo, S, and Fe. Heifers consuming the 25-50-25 supplement in the Stall group initially lost hepatic Cu rapidly but this loss slowed from d 50 to d 100 compared to the Control (P = 0.07), 50-50 (P < 0.05), and 2X-SO4 (P < 0.05) heifers and was similar (P > 0.10) to that in the 5X-SO4 heifers. In the Pen group, total hepatic Cu loss tended to be greater for 25-50-25 and 2X-SO4 compared to 5X-SO4 heifers (P = 0.09 and P = 0.06, respectively); Cu loss in the 50-50 heifers was similar (P > 0.10) to that in the 5X-SO4 heifers. This suggests that supplementing combinations of inorganic and amino acid-complexed Cu was as effective in limiting hepatic Cu loss during antagonism as was increasing dietary Cu levels to five times the NRC recommendation. A combination of 25% CuSO4 , 50% Cu-amino acid complex, and 25% CuO limited liver accumulation of Mo compared to supplements without CuO and could provide a strategic supplementation tool in limiting the systemic effects of Cu antagonism in beef cattle. PMID- 11768125 TI - Use of the bead beater for preparation of Mycobacterium paratuberculosis template DNA in milk. AB - Mycobacterium paratuberculosis is a recognized chronic enteric pathogen that can affect many different species of animals, including primates. It has been suggested that this organism is associated with Crohn's disease in humans, and that milk is a potential source of human exposure to this organism. The limit of the detection of M. paratuberculosis in milk samples by direct PCR was 10(5) cfu/mL if the traditional boiling method was used for template DNA preparation. In this study, an improved method for template DNA preparation was examined. The method involves the use of a bead beater, which breaks up bacterial cell wall mechanically by vibrating bacteria with microbeads at high speed. The effectiveness of this method for lysing M. paratuberculosis cells was compared to that of the freeze-thaw method, and use of commercial kits such as the InstaGene Matrix and the QIAamp Tissue Kit. The bead beater procedure was tested in combination with various cell lysis and template DNA preparation procedures to determine which of these steps improved the limit of detection of PCR assay that amplifies a 413 bp fragment of the IS900 gene. Results showed that the use of the bead beater, in combination with the use of lysis buffer, boiling, and isopropanol precipitation, decreased the limit of detection of M. paratuberculosis in milk by the PCR to 10(2) cfu/mL. The limit of detection was further decreased to 10 cfu/mL when 0.0037% bovine serum albumin was included in the PCR reaction mixtures. The improved assay was 10- to 10(4)-fold more sensitive than the PCR assays using template DNA prepared by other lysis procedures including boiling alone, freeze-thaw plus boiling, or use of commercial kits for lysis. PMID- 11768127 TI - Treatment of pigs experimentally infected with Mycoplasma hyopneumoniae, Pasteurella multocida, and Actinobacillus pleuropneumoniae with various antibiotics. AB - The authors have performed a comparative study of the efficacy of various in-feed medications for the treatment of 5- to 6-week-old specific pathogen-free (SPF) piglets experimentally infected on day 1 with Mycoplasma hyopneumoniae, on day 8 with Pasteurella multocida (serotype A), and on day 15 with Actinobacillus pleuropneumoniae (serotype 2). The treatment started on day 9 and continued for 12 consecutive days, then the piglets were euthanized for examination of macroscopic, histologic, and pathologic lesions and for the presence of mycoplasmas and bacteria in the lungs. Based on the results of clinical observations (respiratory signs, rectal temperature, body weight gain, and feed conversion efficiency), macroscopic and histologic lesions of the lungs, and microbiologic findings, the best results were obtained by treatment of pigs with Econor + chlortetracycline, followed by Tetramutin, Pulmotil, Cyfac, and lincomycin + chlortetracycline. PMID- 11768126 TI - Cloning and characterization of the gene coding for NADPH-sulfite reductase hemoprotein from Actinobacillus pleuropneumoniae and use of the protein product as a vaccine. AB - An expression library was constructed from an Actinobacillus pleuropneumoniae serotype 1 clinical isolate and screened with serum produced in pigs that had been vaccinated with the anionic fraction of a sodium chloride extract. One E. coli transformant was isolated that produced a large amount of a protein with an electrophoretic mobility of about 67,000 molecular mass. The A. pleuropneumoniae derived DNA encoding the protein was localized and characterized by restriction enzyme digestion and nucleotide sequence analysis which showed strong homology with the cysI gene of E. coli. One open reading frame of 1764 bases in length was detected which encoded a cysI protein from serotype 1, with a calculated molecular mass of 66,678. The DNA encoding the protein was labeled with radio isotope and the homologous gene was isolated from an A. pleuropneumoniae serotype 5a library. The serotype 5a gene was the same length, but the cysI protein from serotype 5a was slightly larger (66,849) due to 8 substitutions in the amino acid sequence. Expression plasmids containing cysI from either serotype of A. pleuropneumoniae complemented an E. coli cysI mutant. Pigs vaccinated with the recombinant cysI were protected from challenge with A. pleuropneumoniae of the homologous serotype. PMID- 11768128 TI - Effects of exogenous recombinant interleukin-12 on immune responses and protection against Brucella abortus in a murine model. AB - This study determined if murine interleukin-12 (IL-12) would influence immunity in mice vaccinated with live or killed Brucella abortus strain RB51 (SRB51). Mice received live or gamma-irradiated SRB51 bacteria alone, or with IL-12 (0.5 or 1.0 microg, 2x or 3x), whereas other mice received saline or IL-12 alone. Post vaccination antibody responses to live or killed SRB51 and clearance of live SRB51 from splenic tissue were not influenced by IL-12 treatments. Mice were challenged at 12 weeks with 4 x 10(4) cfu of B. abortus strain 2308 (S2308) and were euthanized 2 weeks later. The highest IL-12 treatment increased (P < 0.05) post-challenge antibody responses when co-administered with killed SRB51. Co administration of 1.0 microg of IL-12 with live SRB51, but not killed SRB51, reduced (P < 0.05) S2308 colonization of splenic tissues. Our data suggest that although IL-12 may augment protective immunity induced by live SRB51, it does not influence protection induced by vaccination with killed SRB51. PMID- 11768129 TI - The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis. AB - Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8 neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID- 11768131 TI - Platelet aggregation responses and virus isolation from platelets in calves experimentally infected with type I or type II bovine viral diarrhea virus. AB - Altered platelet function has been reported in calves experimentally infected with type II bovine viral diarrhea virus (BVDV). The purpose of the present study was to further evaluate the ability of BVDV isolates to alter platelet function and to examine for the presence of a virus-platelet interaction during BVDV infection. Colostrum-deprived Holstein calves were obtained immediately after birth, housed in isolation, and assigned to 1 of 4 groups (1 control and 3 treatment groups). Control calves (n = 4) were sham inoculated, while calves in the infected groups (n = 4 for each group) were inoculated by intranasal instillation with 10(7) TCID50 of either BVDV 890 (type II), BVDV 7937 (type II), or BVDV TGAN (type I). Whole blood was collected prior to inoculation (day 0) and on days 4, 6, 8, 10, and 12 after inoculation for platelet function testing by optical aggregometry by using adenosine diphosphate and platelet activating factor. The maximum percentage aggregation and the slope of the aggregation curve decreased over time in BVDV-infected calves; however, statistically significant differences (Freidman repeated measures ANOVA on ranks, P < 0.05) were only observed in calves infected with the type II BVDV isolates. Bovine viral diarrhea virus was not isolated from control calves, but was isolated from all calves infected with both type II BVDV isolates from days 4 through 12 after inoculation. In calves infected with type I BVDV, virus was isolated from 1 of 4 calves on days 4 and 12 after inoculation and from all calves on days 6 and 8 after inoculation. Altered platelet function was observed in calves infected with both type II BVDV isolates, but was not observed in calves infected with type I BVDV. Altered platelet function may be important as a difference in virulence between type I and type II BVDV infection. PMID- 11768130 TI - Molecular cloning and characterization of beluga whale (Delphinapterus leucas) interleukin-1beta and tumor necrosis factor-alpha. AB - Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are cytokines produced primarily by monocytes and macrophages with regulatory effects in inflammation and multiple aspects of the immune response. As yet, no molecular data have been reported for IL-1beta and TNF-alpha of the beluga whale. In this study, we cloned and determined the entire cDNA sequence encoding beluga whale IL 1beta and TNF-alpha. The genetic relationship of the cytokine sequences was then analyzed with those from several mammalian species, including the human and the pig. The homology of beluga whale IL-1beta nucleic acid and deduced amino acid sequences with those from these mammalian species ranged from 74.6 to 86.0% and 62.7 to 77.1%, respectively, whereas that of TNF-alpha varied from 79.3 to 90.8% and 75.3 to 87.7%, respectively. Phylogenetic analyses based on deduced amino acid sequences showed that the beluga whale IL-1beta and TNF-alpha were most closely related to those of the ruminant species (cattle, sheep, and deer). The beluga whale IL-1beta- and TNF-alpha-encoding sequences were thereafter successfully expressed in Escherichia coli as fusion proteins by using procaryotic expression vectors. The fusion proteins were used to produce beluga whale IL-1beta- and TNF-alpha-specific rabbit antisera. PMID- 11768132 TI - Expression and adhesive ability of gicerin, a cell adhesion molecule, in the pock lesions of chorioallantoic membranes infected with an avian poxvirus. AB - The expression and adhesive activities of gicerin, a cell adhesion protein, in the pock lesions on chicken chorioallantoic membranes (CAM) infected with an avian poxvirus were studied. In normal CAMs, gicerin was found on the flattened epithelial cells, and neurite outgrowth factor (NOF) was in the basement membrane. However, in the pock lesions on infected CAMs, gicerin was overexpressed on the cell membranes of hyperplastic epithelial cells forming thick epithelial layers. Neurite outgrowth factor was also found mainly in the basement membrane, but occasionally showed aberrant expression among hyperplastic cells. In vitro analyses, using the dissociated cells from pock lesions, demonstrated that an anti-gicerin polyclonal antibody inhibit cell aggregation activity and cell adhesion to NOF. These results suggest that gicerin might promote the cell-cell and cell-extracellular matrix protein bindings of the hyperplastic epithelial cells by its homophilic and heterophilic adhesive activities, and contribute to pock formation on the infected CAMs. PMID- 11768133 TI - Identification of genetically diverse sequences (ORF 5) of porcine reproductive and respiratory syndrome virus in a swine herd. AB - The ability of genetically diverse strains of porcine reproductive and respiratory syndrome virus (PRRSV) to coexist in a 1750-sow farm was assessed through the case study describing a chronically infected farm, and also by an animal experiment involving the use of swine bioassay. The case study employed a program of monitoring sera from suckling, nursery, and finishing pigs for the presence of PRRSV by polymerase chain reaction (PCR) and virus isolation (VI). The swine bioassay tested homogenates, consisting of lymphoid and pulmonary tissues, collected from 60 breeding animals from the same farm. The open reading frame (ORF) 5 portion of selected positive PRRSV detected from sera or tissues were nucleic acid sequenced and their phylogenies compared. The results indicated the presence of 3 genetically diverse groups, designated PRRSV-A, -B, and -C. Sequence heterology ranged from 5.8 to 11% between groups. Sequence homology ranged from 98.7 to 99.8% within groups. Swine bioassay verified the presence of PRRSV-A in 1 of 60 animals, and no evidence of strains B or C were detected. This paper indicates that based on the evaluation of ORF 5, genetically diverse strains of PRRSV appear to coexist, although the frequency and significance of this observation is not understood. PMID- 11768135 TI - Heart rate-defined phases of attention, look duration, and infant performance in the paired-comparison paradigm. AB - Four-month-old infants (N = 68) were tested in a paired-comparison familiarization-novelty recognition task in which the length of choice trials was systematically manipulated. Peak look duration during pretest and familiarization periods significantly predicted a dichotomous measure of recognition performance, but recognition was unaffected by choice-trial length. Heart rate (HR) was simultaneously assessed during the task, and the amount of time infants spent in various HR-defined phases of attention was assessed. Longer durations of looking during pretest and familiarization were significantly associated with more time spent in both sustained attention (SA) and attention termination (AT). Of these two variables, only individual differences in AT accounted for significant variance in recognition memory performance. A final analysis addressed the possibility that individual differences in AT mediated the relation between look duration and recognition performance. These findings provide support for the hypothesis that individual differences in the disengagement of attention underlie the relation between look duration and cognitive performance in early to midinfancy. PMID- 11768134 TI - Transmission of porcine reproductive and respiratory syndrome virus from persistently infected sows to contact controls. AB - The objective of this study was to determine if porcine reproductive and respiratory syndrome virus (PRRSV) could persist in non-pregnant sows and if persistently infected sows could transmit virus to naive contact controls. Twelve PRRSV-naive, non-pregnant sows (index sows) were infected with a field isolate of PRRSV and housed in individual isolation rooms for 42 to 56 days postinfection. Following this period, 1 naive contact sow was placed in each room divided by a gate allowing nose-to-nose contact with a single index sow. Index sows were not viremic at the time of contact sow entry. Virus nucleic acid was detected by polymerase chain reaction, and infectious virus was detected by virus isolation in sera from 3 of the 12 contact sows at 49, 56, and 86 days postinfection. All 3 infected contacts developed PRRSV antibodies. Virus nucleic acid was detected in tissues of all of the 12 index sows at 72 or 86 days postinfection. Nucleic acid sequencing indicated that representative samples from index and infected contacts were homologous (> 99%) to the PRRSV used to infect index sows at the onset of the study. This study demonstrates that PRRSV can persist in sows and that persistently infected sows can transmit virus to naive contact animals. PMID- 11768136 TI - Exposure to interparental conflict and children's adjustment and physical health: the moderating role of vagal tone. AB - Physiological regulation, as indexed by baseline vagal tone and delta vagal tone (the change in vagal tone during an attention-demanding or challenging task), was examined as a moderator in the relations between exposure to verbal and physical parental marital conflict and children's adjustment and physical health. Higher vagal tone was posited to serve a protective function (i.e., buffer) for children exposed to higher levels of marital conflict. Seventy-five 8- to 12-year-olds and their mothers completed measures of parental conflict, and children's adjustment and physical health. Children's vagal tone was assessed during baseline conditions and during exposure to an audiotaped interadult argument. Results indicate that higher vagal tone buffered children against increased externalizing, internalizing, and health problems related to exposure to more frequent marital conflict, especially verbal conflict. Further, higher levels of delta vagal tone protected boys against externalizing problems associated with verbal conflict, and health problems associated with physical conflict. PMID- 11768138 TI - The influence of shape similarity and shared labels on infants' inductive inferences about nonobvious object properties. AB - This study examined the influence of object labels and shape similarity on 16- to 21-month-old infants' inductive inferences. In three experiments, a total of 144 infants were presented with novel target objects with or without a nonobvious property, followed by test objects that varied in shape similarity to the target. When objects were not labeled, infants generalized the nonobvious property to test objects that were highly similar in shape (Experiment 1). When objects were labeled with novel nouns, infants relied both on shape similarity and shared labels to generalize properties (Experiment 2). Finally, when objects were labeled with familiar nouns, infants generalized the properties to those objects that shared the same label, regardless of shape similarity (Experiment 3). The results of these experiments delineate the role of perceptual similarity and conceptual information in guiding infants' inductive inferences. PMID- 11768137 TI - Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. AB - Phenylketonuria (PKU) is a genetic disorder characterized by hyperphenylalaninemia. Treatment involves dietary phenylalanine restriction to prevent mental retardation. Because phenylalanine is involved in tyrosine synthesis and tyrosine is a catecholamine precursor, low tyrosine may lead to brain dopamine deficiencies. Because dopamine is involved in the modulation of prefrontally orchestrated executive functions, deficiencies may lead to executive impairments. Despite treatment, impairments in executive cognitive functions have been reported in young children with PKU. Outcome beyond middle childhood has not been extensively investigated. In this study, PKU-affected adolescents (N = 18) with normal-range IQ scores completed neuropsychological tests, and their performance was compared with unaffected peers (N = 16) and chronically ill controls (N = 17). Results demonstrated that the overall performance of the PKU group did not differ from that of the other two groups, but that performance of the PKU proband was associated with phenylalanine and tyrosine levels, and most strongly with phenylalanine-to-tyrosine ratios at several points in development. These findings provide a preliminary test of the dopamine hypothesis of PKU as it applies to adolescents and young adults. PMID- 11768139 TI - One cow does not an animal make: young children can extend novel words at the superordinate level. AB - Six match-to-sample picture/object selection experiments were designed to explore children's knowledge about superordinate words (e.g., "food") and how they acquire this knowledge. Three factors were found to influence the learning and extension of superordinate words in 3- to 5-year-old children (N = 230): The number of standards (one versus two), the type of standards presented (from different basic-level categories versus from the same basic-level category), and the nature of the object representations used (pictures versus objects). A different pattern of superordinate word acquisition was found between 3-year-olds and 4- and 5-year-olds. Although 4- and 5-year-olds could learn and extend novel words to superordinate categories in the presence of two picture exemplars from different categories or a single three-dimensional (3-D) exemplar, 3-year-olds could do so only in the presence of two 3-D exemplars. These findings indicate that young children's acquisition of superordinate words is influenced by multiple factors and that there is a developmental progression from multiple exemplars to single exemplars in superordinate word learning. PMID- 11768140 TI - How much does a shared name make things similar? Linguistic labels, similarity, and the development of inductive inference. AB - This article examines the development of inductive generalization, and presents a model of young children's induction and two experiments testing the model. The model specifies contribution of linguistic labels and perceptual similarity to young children's induction and predicts a correspondence between similarity judgment and induction of young children. In Experiment 1, 4- to 5-year-olds, 7- to 8-year-olds, and 11- to 12-year-olds were presented with triads of schematic faces (a Target and two Test stimuli), which varied in perceptual similarity, with one of the Test stimuli sharing a linguistic label with the Target, and another having a different label. Participants were taught an unobservable biological property about the Target and asked to generalize the property to one of the Test stimuli. Although 4- to 5-year-olds' proportions of label-based inductive generalizations varied with the degree of perceptual similarity among the compared stimuli, 11- to 12-year-olds relied exclusively on labels, and 7- to 8-year-olds appeared to be a transitional group. In Experiment 2 these findings were replicated using naturalistic stimuli (i.e., photographs of animals), with perceptual similarity manipulated by "morphing" naturalistic pictures into each other in a fixed number of steps. Overall results support predictions of the model and point to a developmental shift from treating linguistic labels as an attribute contributing to similarity to treating them as markers of a common category-a shift that appears to occur between 8 and 11 years of age. PMID- 11768141 TI - Problem solving, contention, and struggle: how siblings resolve a conflict of interests. AB - In a laboratory setting, 48 sibling dyads age 4 and 6 or 6 and 8 years negotiated the division of six toys. Findings revealed that, in general, children reached divisions while using a preponderance of constructive problem-solving strategies, rather than contentious tactics. The degree of conflict of interests and the quality of sibling relationships predicted the children's use of problem-solving and contentious negotiation strategies, and was related to the types of resolutions achieved. Dyads experiencing low conflict of interests resolved their differences quickly. High conflict of interests coupled with positive relationships and constructive negotiation resulted in longer negotiations and creative, agreeable resolutions. High conflict of interests coupled with more negative relationships and destructive negotiations resulted in children's failures to reach agreement. Developmental differences indicated that older siblings within the pairs took the lead in negotiation, and benefited slightly more from the divisions. Furthermore, children in older dyads were more sophisticated and other oriented in their negotiations. PMID- 11768142 TI - The development of multiple domains of child and adolescent self-concept: a cohort sequential longitudinal design. AB - The development of child and adolescent self-concept was examined as a function of the self-concept domain, social/developmental/educational transitions, and gender. In two overlapping age cohorts of public school students (Ns = 936 and 984), five dimensions of self-concept were evaluated every 6 months in a manner that spanned grades 3 through 11 (representing the elementary, middle, and high school years). Domains of self-concept included academic competence, physical appearance, behavioral conduct, social acceptance, and sports competence. Structural equation modeling addressed questions about the stability of individual differences over time. Multilevel modeling addressed questions about mean-level changes in self-concept over time. Significant effects emerged with regard to gender, age, dimension of self-concept, and educational transition. PMID- 11768143 TI - The relations of regulation and negative emotionality to Indonesian children's social functioning. AB - The purpose of this study was to examine the relations of individual differences in regulation and negative emotionality to 127 third-grade Indonesian children's social skills/low externalizing problem behavior, sociometric status, and shyness. Parents and multiple teachers provided information on children's regulation, negative emotionality, and social functioning; peer sociometric information on liking and social behavior was obtained; and children reported on their self-regulation. In general, children's low socially appropriate behavior/ high problem behavior and rejected peer status were related to low dispositional regulation and high negative emotionality (intense emotions and anger), and regulation and negative emotionality (especially teacher rated) sometimes accounted for unique (additive) variance in children's social functioning. Adult reported shyness was related to low peer nominations of disliked/fights (although shy children were not especially liked), low adult-reported regulation, and (to a lesser degree) low teacher-rated negative emotionality. Findings are compared with work on regulation, negative emotionality, social competence, and shyness in other countries. PMID- 11768144 TI - Free- time activities in middle childhood: links with adjustment in early adolescence. AB - This study assessed links between free-time activities in middle childhood (hobbies, sports, toys and games, outdoor play, reading, television viewing, and hanging out) and school grades, conduct, and depression symptoms both concurrently and 2 years later, in early adolescence. It also explored two mechanisms that might underlie activity-adjustment links: whether the social contexts of children's activities mediate these links, child effects explain these connections, or both. Participants were 198 children (M = 10.9 years, SD = .54 years) in Year 1, and their parents. In home interviews in Years 1 and 3 of the study, mothers rated children's conduct problems, children reported on their depression symptoms, and information was collected on school grades from report cards. In seven evening phone interviews, children reported on the time they spent in free-time activities during the day of the call and their companions in each activity. Links were found between the nature of children's free-time activities and their adjustment. The social contexts of free-time activities explained activity-adjustment links to a limited degree; with respect to child effects, evidence also suggested that better adjusted children became more involved in adaptive activities over time. PMID- 11768145 TI - Change in family income-to-needs matters more for children with less. AB - Hierarchical linear modeling was used to model the dynamics of family income-to needs for participants of the National Institute of Child Health and Human Development Study of Early Child Care (N = 1,364) from the time that children were 1 through 36 months of age. Associations between change in income-to-needs and 36-month child outcomes (i.e., school readiness, receptive language, expressive language, positive social behavior, and behavior problems) were examined. Although change in income-to-needs proved to be of little importance for children from nonpoor families, it proved to be of great importance for children from poor families. For children in poverty, decreases in income-to needs were associated with worse outcomes and increases were associated with better outcomes. In fact, when children from poor families experienced increases in income-to-needs that were at least 1 SD above the mean change for poor families, they displayed outcomes similar to their nonpoor peers. The practical importance and policy implications of these findings are discussed. PMID- 11768146 TI - Effects of poverty and maternal depression on early child development. AB - Researchers have renewed an interest in the harmful consequences of poverty on child development. This study builds on this work by focusing on one mechanism that links material hardship to child outcomes, namely the mediating effect of maternal depression. Using data from the National Maternal and Infant Health Survey, we found that maternal depression and poverty jeopardized the development of very young boys and girls, and to a certain extent, affluence buffered the deleterious consequences of depression. Results also showed that chronic maternal depression had severe implications for both boys and girls, whereas persistent poverty had a strong effect for the development of girls. The measures of poverty and maternal depression used in this study generally had a greater impact on measures of cognitive development than motor development. PMID- 11768147 TI - Ethnic differences in the effect of parenting on gang involvement and gang delinquency: a longitudinal, hierarchical linear modeling perspective. AB - This study examined the relative influence of peer and parenting behavior on changes in adolescent gang involvement and gang-related delinquency. An ethnically diverse sample of 300 ninth-grade students was recruited and assessed on eight occasions during the school year. Analyses were conducted using hierarchical linear modeling. Results indicated that, in general, adolescents decreased their level of gang involvement over the course of the school year, whereas the average level of gang delinquency remained constant over time. As predicted, adolescent gang involvement and gang-related delinquency were most strongly predicted by peer gang involvement and peer gang delinquency, respectively. Nevertheless, parenting behavior continued to significantly predict change in both gang involvement and gang delinquency, even after controlling for peer behavior. A significant interaction between parenting and ethnic and cultural heritage found the effect of parenting to be particularly salient for Black students, for whom higher levels of behavioral control and lower levels of lax parental control were related to better behavioral outcomes over time, whereas higher levels of psychological control predicted worse behavioral outcomes. PMID- 11768148 TI - Extending research on the consequences of parenting style for Chinese Americans and European Americans. AB - This study examined the effects of parent-adolescent relationships on school performance to provide a clearer understanding of why authoritative parenting does not have as beneficial effects for Asian Americans as it does for European Americans. Over 500 adolescents of Chinese- (148 first and 176 second generation) and European-descent (208 primarily third generation or more) families from seven different high schools completed measures of (1) parenting style, (2) parent adolescent closeness (cohesion subscale from the Family Adaptability and Cohesion Environment Scales II and relationship satisfaction), and (3) school performance. Positive effects of both authoritative parenting and relationship closeness on school performance were found for European Americans and, to some extent, second generation Chinese, but not first-generation Chinese. These effects were also stronger for European Americans than first-generation Chinese. Through examination of the mediating role of parent-adolescent relationships, this study also found that among European American families, the beneficial effects of authoritative parenting are explained through relationship closeness. PMID- 11768149 TI - The home environments of children in the United States part I: variations by age, ethnicity, and poverty status. AB - Although measures of the home environment have gained wide acceptance in the child development literature, what constitutes the "average" or 'typical" home environment in the United States, and how this differs across ethnic groups and poverty status is not known. Item-level data from the National Longitudinal Survey of Youth on four age-related versions of the Home Observation for Measurement of the Environment-Short Form (HOME-SF) from five biennial assessments (1986-1994) were analyzed for the total sample and for four major ethnic groups: European Americans, Asian Americans, African Americans, and Hispanic Americans. The percentages of homes receiving credit on each item of all four versions of the HOME-SF are described. For the majority of items at all four age levels differences between poor and nonpoor families were noted. Differences were also obtained among African American, European American, and Hispanic American families, but the magnitude of the effect for poverty status was greater than for ethnicity, and usually absorbed most of the ethnic group effects on HOME SF items. For every item at every age, the effects of poverty were proportional across European American, African American, and Hispanic American groups. PMID- 11768150 TI - The home environments of children in the United States part II: relations with behavioral development through age thirteen. AB - This study examined the frequency with which children were exposed to various parental actions, materials, events, and conditions as part of their home environments, and how those exposures related to their well-being. Part 1 focused on variations by age, ethnicity, and poverty status. In Part 2 of the study, relations between major aspects of the home environment (including maternal responsiveness, learning stimulation, and spanking) and developmental outcomes for children from birth through age 13 were investigated. The outcomes examined were early motor and social development, vocabulary development, achievement, and behavior problems. These relations were examined in both poor and nonpoor European American, African American, and Hispanic American families using hierarchical linear modeling. The most consistent relations found were those between learning stimulation and children's developmental status, with relations for parental responsiveness and spanking varying as a function of outcome, age, ethnicity, and poverty status. The evidence indicated slightly stronger relations for younger as compared with older children. PMID- 11768151 TI - Child development and public policy: toward a dynamic systems perspective. AB - Little theoretical work exists that proposes general mechanisms for how public policies may influence child development. This article argues that dynamic systems theories may be useful in illuminating such processes, as well as highlighting gaps in current research at the intersection of public policy analysis and developmental science. A brief review of dynamic systems theories as they are currently utilized in other areas of developmental science is provided, as well as a statement of why they may help advance research in public policy and child development. Five principles of dynamic systems theories are presented and discussed using examples from research that address the question, "How do current antipoverty and welfare reform policies affect children?" Also presented are examples of hypotheses and research questions that each principle may generate for future work. The concluding section presents challenges that each principle poses for research methodology, and potential uses of the dynamic systems approach for developing and integrating policy and program initiatives. PMID- 11768152 TI - Mixed-chain phospholipids: structures and chain-melting behavior. AB - It has long been established that diacyl phospholipids isolated from animal cell membranes are predominantly of a mixed-chain variety, meaning that the sn-1 and sn-2 acyl chains are saturated and unsaturated acyl chains, respectively. In general, monoenoic and dienoic acids are found in the sn-2 acyl chain of phosphatidylcholine (PtdCho), whereas polyenoic acids are in phosphatidylethanolamine (PtdEth). These unsaturated chains contain only cis double bonds, which are always methylene-interrupted. In recent years, the structures and the chain-melting behavior of mixed-chain PtdCho and PtdEth have been systematically studied in this laboratory. Specifically, we have examined the effects of chain unsaturation of the sn-2 acyl chain on the phase transition temperature (Tm) of many PtdCho and PtdEth by high-resolution differential scanning calorimetry (DSC). The Tm values, for instance, obtained from all unsaturated mixed-chain PtdEth derived from a common precursor can be grouped together according to their chemical formula to form a Tm-diagram. Hence, all the Tm values can be compared simply, systematically, and simultaneously using the Tm diagram. In addition, the energy-minimized structures of mixed-chain phospholipids containing different numbers/positions of methylene-interrupted cis double bonds have been simulated by molecular mechanics calculations (MM). In this review, the results of our MM and DSC studies carried out with various mixed chain phospholipids are summarized. In addition, we emphasize that the combined approach of MM and DSC yields unique information that can correlate the various Tm-profiles seen in the Tm-diagram with the structural variation of mixed-chain lipids as caused by the introduction of different numbers/positions of methylene interrupted cis-double bonds. PMID- 11768153 TI - Inhibitory effect of conjugated linoleic acid on linoleic acid elongation in transformed yeast with human elongase. AB - Conjugated linoleic acid (CLA; 18:2) refers to a group of positional and geometric isomers derived from linoleic acid (LA; delta9,12-18:2). Using a growing baker's yeast (Saccharomyces cerevisiae) transformed with human elongase gene, we examined the inhibitory effect of CLA at various concentrations (10, 25, 50, and 100 microM) on elongation of LA (25 microM) to eicosadienoic acid (EDA; delta11,14-20:2). Among four available individual CLA isomers, only c9,t11- and t10,c12-isomers inhibited elongation of LA to EDA. The extent of inhibition (ranging from 20 to 60%) was related to the concentration of CLA added to the medium. In the meantime, only these two isomers, when added at 50 microM to the media, were elongated to conjugated FDA (c11,t13- and t12,c14-20:2) by the same recombinant elongase at the rate of 28 and 24%, respectively. The inhibitory effect of CLA on LA elongation is possibly due to competition between CLA isomers and LA for the recombinant elongase. Thus, results from this study and a previous study suggest that the biological effect of CLA is exerted through its inhibitory effect on delta6-desaturation as well as elongation of LA which results in a decrease in long-chain n-6 fatty acids and consequently the eicosanoid synthesis. PMID- 11768154 TI - A unique antioxidant activity of phosphatidylserine on iron-induced lipid peroxidation of phospholipid bilayers. AB - The relationship between the antioxidant effect of acidic phospholipids, phosphatidic acid (PA), phosphatidylglycerol (PG) and phosphatidylserine (PS), on iron-induced lipid peroxidation of phospholipid bilayers and their abilities to bind iron ion was examined in egg yolk phosphatidylcholine large unilamellar vesicles (EYPC LUV). The effect of each acidic phospholipid added to the vesicles at 10 mol% was assessed by measuring phosphatidylcholine hydroperoxides (PC-OOH) and thiobarbituric acid-reactive substances. The addition of dipalmitoyl PS (DPPS) showed a significant inhibitory effect, although the other two acidic phospholipids, dipalmitoyl PA (DPPA) and dipalmitoyl PG (DPPG), did not exert the inhibition. Neither dipalmitoyl PC (DPPC) nor dipalmitoyl phophatidylethanolamine (DPPE) showed any remarkable inhibition on this system. None of the tested phospholipids affected the lipid peroxidation rate remarkably when the vesicles were exposed to a water-soluble radical generator. The iron-binding ability of each phospholipid was estimated on the basis of the amounts of iron recovered in the chloroform/methanol phase after separation of the vesicle solution to water/methanol and chloroform/methanol phases. EYPC LUV containing DPPS, DPPA, and DPPG had higher amounts of bound iron than those containing DPPC and DPPE, indicating that these three acidic phospholipids possess an iron-binding ability at a similar level. Nevertheless, only DPPS suppressed iron-dependent decomposition of PC-OOH significantly. Therefore, it is likely that these three acidic phospholipids possess a significant iron-binding ability, although this ability per se does not warrant them antioxidative activities. The ability to suppress the iron-dependent decomposition of PC-OOH may explain the unique antioxidant activity of PS. PMID- 11768155 TI - Antioxidative activity of 3,4-dihydroxyphenylacetic acid and caffeic acid in rat plasma. AB - The purpose of the present paper is to study and compare in vitro the inhibitory effect of 3,4-dihydroxyphenylacetic acid (DOPAC) and caffeic acid (CA) on lipid peroxidation in rat plasma. Rat plasma was oxidized at 37 degrees C by the radical initiators 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) or 2,2' azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). The consumption of endogenous alpha-tocopherol (alpha-TOH) and the accumulation of conjugated diene hydroperoxides were measured by high-performance liquid chromatography and by ultraviolet spectroscopy, respectively. Alpha-TOH was consumed at the same rate in the presence of 20 mM AAPH or 2 mM MeO-AMVN. DOPAC and CA suppressed the alpha TOH consumption in a dose-dependent manner. A concentration of 50 microM of both phenolic acids was sufficient to induce a lag phase and to delay the rate of alpha-TOH consumption. The effect was more pronounced in rat plasma oxidation by AAPH than by MeO-AMVN. CA spared vitamin E more effectively than DOPAC in both oxidations. DOPAC and CA suppressed the formation of conjugated diene hydroperoxides. DOPAC and CA at concentration 50 microM suppressed alpha-TOH consumption during oxidation of soybean phosphatidylcholine (2.8 mM) multilamellar vesicles containing 15 microM alpha-TOH, in which the lipophilic initiator 2,2'-azobis (2,4-dimethylvaleronitrile) (6 mM) was incorporated. In conclusion, we demonstrated that DOPAC and CA in micromolar concentrations have antioxidant activity in rat plasma, a medium very close to the conditions in vivo, suggesting that supplementation with the phenolic acids will provide significant antioxidant protection. PMID- 11768157 TI - Absorption and effects of 3-(N-phenylamino)-1,2-propanediol esters in relation to toxic oil syndrome. AB - Toxic Oil Syndrome (TOS) was an epidemic disease related to the consumption of rapeseed oil denatured with aniline that made its sudden appearance in Spain in 1981. The fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP), which is a chemical class of by-products resulting from the reaction of aniline with oil components, have shown a strong association with TOS-related oils. These compounds also show some structural similarities to platelet-activating factor (PAF). In search of a toxic agent that could explain the widespread systemic effects observed in TOS patients, we investigated the intestinal absorption and biotransformation of the different PAP esters found in TOS-related oil samples and the possible pathophysiological effect of these mediators and their metabolic products if acting as PAF analogs. Results indicate that PAP esters are absorbed in the gastrointestinal tract and are distributed and stored in different organs, particularly in the liver and brown adipose tissue. PAP in these organs showed different patterns of fatty acids, indicating the ability of the gastrointestinal tract to modify the fatty acid composition of the parent PAP. Thus, the fatty acid profile of the PAP esters found in intestine appears to be related to the type of oil used as vehicle. Some of these PAP esters, when a long acyl chain was present in the sn-1 position of the molecule, showed an inhibitory effect on the PAF synthesis. This is an important observation in line with the systemic nature of the disease. PMID- 11768156 TI - Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. AB - Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2 cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids. PMID- 11768158 TI - Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer and prevents the formation of cholesterol gallstones in inbred mice. AB - We have recently synthesized fatty acid bile acid conjugates (FABAC) that were able to reduce and retard cholesterol crystallization in model and human biles. When given orally, they prevented the formation of cholesterol crystals in the bile of hamsters. The aim of the present study was to determine whether the FABAC are cholesterol solubilizers, whether they can dissolve pre-existing crystals, whether they can prevent the formation of cholesterol gallstones, and to investigate the optimal type of bond between the fatty acid and bile acid. The presence of cholesterol crystals was determined by light microscopy, and the total crystal mass of precipitated crystals was measured by chemical means. Inbred (C57J/L) mice on a lithogenic diet were used to evaluate cholesterol crystal formation, dissolution, and gallstone formation in vivo. Arachidyl amido cholanoic acid (Aramchol) was the FABAC used in the present experiments. At equimolar amounts, the cholesterol-solubilizing capacity of Aramchol was higher than that of taurocholate and similar to that of phosphatidylcholine. The addition of Aramchol dissolved approximately 50% of pre-existing crystals in model bile solutions. The same phenomenon was demonstrated in human bile ex vivo, with a dose-response effect. All inbred mice developed cholesterol crystals in bile after 10-14 d on the lithogenic diet. Thereafter, supplementation of the diet with Aramchol progressively reduced the proportion of mice with crystals to 25% after 28 d. On the lithogenic diet, 100% of inbred mice developed cholesterol gallstones in the gallbladder by day 21. None of the mice whose diet was supplemented with 0.5 mg or 1.0 mg of Aramchol/d developed stones or crystals. FABAC are a new class of molecules that are cholesterol solubilizers and which are able to dissolve cholesterol crystals in bile. Upon oral administration, they dissolve pre-existing cholesterol crystals and prevent the formation of gallstones in gallstone-susceptible mice. PMID- 11768159 TI - Alterations in fatty acid composition of tissue phospholipids in the developing retinal dystrophic rat. AB - Alterations in lipid composition occur in the retinal pigment epithelium and photoreceptor cells of the Royal College of Surgeons (RCS) dystrophic rat, a model for inherited retinal degeneration. With respect to lipid composition of nonretinal tissues, the developmental timing of lipid alterations and the incidence of dystrophy are unknown. We determined the fatty acid composition in choline phosphoglycerides (ChoGpl) and ethanolamine phosphoglycerides (EtnGpl) in the brain, liver, and retina from dystrophic RCS rats and from their nondystrophic congenics (controls) at the ages of 3 and 6 wk. At 3 wk, the fatty acid compositions were specific to individual phospholipid classes without any difference between dystrophic and nondystrophic tissues. In plasma phospholipids, there was an age-related increase in the relative contents of monounsaturated and n-3 polyunsaturated fatty acids, with only minor differences between dystrophic and nondystrophic rats. At 6 wk, the fatty acid compositions in ChoGpl and EtnGpl from dystrophic brain and retina were significantly different from those of nondystrophics. The effect of strain on developmental changes in brain fatty acid composition was significant for 18:0 and 22:6n-3 in EtnGpl and for 16:0, 18:0, 18:1n-9, and 20:4n-6 in ChoGpl. The brain ChoGpl fatty acid composition in nondystrophic rats was similar at 6 wk to that of normal rats, and there were almost no postweaning changes in the dystrophics. In retinal phospholipids, the effect of dystrophy was to increase the 20:4n-6 content in EtnGpl and to decrease 22:6n-3 in ChoGpl. The 18:2n-6 and 22:6n-3 contents in dystrophic liver ChoGpl were also significantly affected, while no difference was observed in the EtnGpl fraction. The dystrophy affected the phospholipid fatty acid developmental changes in a tissue- and class-specific manner. Fatty acid metabolism could be selectively altered in neural and nonneural tissues of developing dystrophic RCS rats. PMID- 11768160 TI - Biosynthesis and tissue deposition of docosahexaenoic acid (22:6n-3) in rainbow trout (Oncorhynchus mykiss). AB - Rainbow trout (Oncorhynchus mykiss) weighing ca. 5 g and previously acclimated for 8 wk on a diet comprising vegetable oil (11%), fish meal (5%), and casein (48%) as the major constituents were fed a pulse of diet containing deuterated (D5) (17,17,18,18,18)-18:3n-3 ethyl ester. The synthesis and tissue distribution of D5-22:6n-3 was determined 3, 7, 14, 24, and 35 d after the pulse. The whole body accumulation of D5-22:6n-3 was linear over the first 7 d, corresponding to a rate of 0.54 +/- 0.12 microg D5-22:6n-3/g fish/mg D5-18:3n-3 eaten/d. Maximal accretion of D5-22:6n-3 was 4.3 +/- 1.2 microg/g fish/mg of D5-18:3n-3 eaten after 14 d. The amount of D5-22:6n-3 peaked in liver at day 7, in brain and eyes at day 24, and plateaued after day 14 in visceral and eye socket adipose tissue and in the whole fish. The majority of D5-22:6n-3 was found in the carcass (remaining tissues minus the above tissues analyzed separately) at all times. On a per milligram lipid basis, liver and eyes had the highest concentration of D5 22:6n-3. The experimental diet also contained 21:4n-6 ethyl ester as a marker to estimate the amount of food eaten by individual fish. From such estimates it was calculated that the great majority of the D5-tracer was catabolized, with the combined recovery of D5-18:3n-3 plus D5-22:6n-3 being 2.6%. The recovery of 21:4n 6 was 57.6%. The concentration of 22:6n-3 in the fish decreased during the 13-wk period, and the amount of 22:6n-3 synthesized from 18:3n-3 was only about 5% of that obtained directly from the fish meal in the diet. PMID- 11768161 TI - Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF-7 and SW480 cancer cells. AB - The relationship between growth and alterations in arachidonic acid (AA) metabolism in human breast (MCF-7) and colon (SW480) cancer cells was studied. Four different fatty acid preparations were evaluated: a mixture of conjugated linoleic acid (CLA) isomers (c9,t11, t10,c12, c11,t13, and minor amounts of other isomers), the pure c9,t11-CLA isomer, the pure t10,c12-CLA isomer, and linoleic acid (LA) (all at a lipid concentration of 16 microg/mL). 14C-AA uptake into the monoglyceride fraction of MCF-7 cells was significantly increased following 24 h incubation with the CLA mixture (P < 0.05) and c9,t11-CLA (P < 0.02). In contrast to the MCF-7 cells, 14C-AA uptake into the triglyceride fraction of the SW480 cells was increased while uptake into the phospholipids was reduced following treatment with the CLA mixture (P < 0.02) and c9,t11-CLA (P < 0.05). Distribution of 14C-AA among phospholipid classes was altered by CLA treatments in both cell lines. The c9,t11-CLA isomer decreased (P < 0.05) uptake of 14C-AA into phosphatidylcholine while increasing (P < 0.05) uptake into phosphatidylethanolamine in both cell lines. Both the CLA mixture and the t10,c12 CLA isomer increased (P < 0.01) uptake of 14C-AA into phosphatidylserine in the SW480 cells but had no effect on this phospholipid in the MCF-7 cells. Release of 14C-AA derivatives was not altered by CLA treatments but was increased (P < 0.05) by LA in the SW480 cell line. The CLA mixture of isomers and c9,t11-CLA isomer inhibited 14C-AA conversion to 14C-prostaglandin E2 (PGE2) by 20-30% (P < 0.05) while increasing 14C-PGF2alpha by 17-44% relative to controls in both cell lines. LA significantly (P < 0.05) increased 14C-PGD2 by 13-19% in both cell lines and increased 14C-PGE2 by 20% in the SW480 cell line only. LA significantly (P < 0.05) increased 5-hydroperoxyeicosatetraenoate by 27% in the MCF-7 cell line. Lipid peroxidation, as determined by increased levels of 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), was observed following treatment with c9,t11-CLA isomer in both cell lines (P < 0.02) and with t10,c12-CLA isomer in the MCF-7 cell line only (P < 0.05). These data indicate that the growth-promoting effects of LA in the SW480 cell line may be associated with enhanced conversion of AA to PGE2 but that the growth-suppressing effects of CLA isomers in both cell lines may be due to changes in AA distribution among cellular lipids and an altered prostaglandin profile. PMID- 11768162 TI - An octaethylene glycol monododecyl ether-based mixed micellar assay for determining the lipid acyl hydrolase activity of patatin. AB - Patatin was extracted from potato tubers (Solanum tuberosum L. cv. Spunta) and purified to homogeneity by ammonium sulfate salt fractionation and one sole chromatographic step. A spectrophotometric mixed micellar assay for patatin lipid acyl hydrolase (LAH) activity was designed with the detergent octaethylene glycol monododecyl ether (C12E8). Patatin LAH used p-nitrophenyl butyrate (PNP-butyrate) as substrate when solubilized in (C12E8) micelles. In the mixed micellar system, patatin LAH responds to the PNP-butyrate surface concentration expressed as mol% (= [PNP-butyratel x 100/([detergentl critical micellar concentration)) and not to the molarity of PNP-butyrate. The kinetic parameters were determined; Vmax was independent of the mixed micelle concentration, as was Km, when expressed as mol%. However, Km was dependent on C12E8 concentration when expressed in molar concentration. C12E8/PNP-butyrate proved to be a reliable system for assaying patatin LAH activity and is superior to the commonly used Triton X-100 and SDS methods. It permits investigation of the substrate requirements of patatin LAH activity because the concentration-independent Km can be determined both in mol% and as the absolute number of substrate molecules per micelle. In addition, the detergent did not affect the enzyme activity. PMID- 11768163 TI - Trans- and cis-octadecenoic acid isomers in the hump and milk lipids from Camelus dromedarius. AB - The distribution profiles of individual trans- as well as cis-18:1 isomers from the fat prepared from the hump adipose tissue and the milk from Camelus dromedarius (the single-humped Arabian species) are described. Gas-liquid chromatography on two capillary columns with different polarities and lengths were used for this purpose in combination with argentation thin-layer chromatography. A comparison of the profiles established is made with that of true ruminant fats. In the fats from the dromedarius as well as from true ruminants, the trans-18:1 isomers have their ethylenic bonds in all positions between delta4 and delta16. The prominent trans isomer is the 11-18:1 (vaccenic) acid in all species, and the complete distribution profiles are quite similar. Concerning the cis isomers, the prominent isomer is oleic acid, followed by cis vaccenic acid, as in true ruminant fats. Other cis isomers encompass the delta6-8 and the delta12 to delta15 isomers. Camelidae (suborder Tylopoda) and Bovidae (suborder Ruminantia) have evolved independently since the Eocene, that is for approximately 50 million years. Despite this considerable period, and the profound differences in anatomy, morphology, physiology, ecological and dietary habits between the extant species of these suborders, the rumen microflora has continued to synthesize the same trans- and cis-octadecenoic acid isomers, in comparable proportions, at least as deduced from their composition profiles. We conclude that the trans-18:1 acid profile is not intrinsically species-dependent, but it can be affected by the nature and the proportions of dietary unsaturated fatty acids that themselves depend on the feed, and that may be species-specific. PMID- 11768164 TI - Transforming growth factor beta in human milk does not change in response to modest intakes of docosahexaenoic acid. AB - Long-chain polyunsaturated fatty acids have been associated with aspects of immune regulation including cytokine production. The purpose of this study was to investigate the effect of maternal dietary supplementation with tuna oil, rich in docosahexaenoic acid (DHA), on the concentration of transforming growth factor beta 1 (TGFbeta1) and TGFbeta2 in breast milk. In this randomized, dietary intervention trial, mothers of term infants consumed a daily supplement of 2000 mg oil containing either placebo (n = 40), 300 mg DHA (n = 40), or 600 mg DHA (n = 40). The DHA increase in milk and plasma was proportional to dietary DHA. There was no relationship between milk DHA status and TGFbeta1 and TGFbeta2 levels. PMID- 11768165 TI - Nicotine-environmental risk factors for initiation. Two principles, one host. PMID- 11768166 TI - Understanding environmental, situational and intrapersonal risk and protective factors for youth tobacco use: the Theory of Triadic Influence. PMID- 11768167 TI - Pharmacology of neuronal nicotinic acetylcholine recceptors: effects of acute and chronic nicotine. AB - Neuronal nicotinic acetylcholine receptors mediate nicotine's diverse effects on the brain, spinal cord and autonomic nervous system. These receptors are composed of alpha and beta subunits. Eight different alpha and three different beta subunits have been identified in vertebrate nervous systems, giving rise to the possibility of multiple subtypes of nicotinic receptors, defined by their constituent subunits. The pharmacological and channel conductance properties of the recombinant receptor subtypes studied in cellular expression systems differ from one another. In addition, the regulation of the receptor density and function during and after acute and chronic exposure to nicotine appears to differ among the subtypes. The predominant receptor subtypes in specific brain regions and peripheral neurons are beginning to be identified and their characteristics studied using new ligands and methods. As more is learned of the differences among the receptor subtypes, it should be possible to identify which specific subtype mediates a specific function within the nervous system and which subtypes are associated with the reinforcing and addictive actions of nicotine. PMID- 11768168 TI - Use of knock-out mice to determine the molecular basis for the actions of nicotine. AB - Recombinant DNA techniques have been used to identify the family of molecules that mediate nicotine's effects on the brain. Nicotine binds and activates nicotinic acetylcholine receptors (nAChRs) which are made up of combinations of individual nicotinic subunits. It is important to determine which of the many possible subunit combinations are responsible for the physiological and behavioral effects of nicotine that lead to addiction. Molecular genetic tools such as antisense strategies have been useful in elucidating the electrophysiological properties of nAChRs in different tissues. Use of knock-out mice lacking individual nAChR subunits has also begun to elucidate how nicotine exerts its actions from the molecular level to the behavioral level. Experiments using mice lacking the beta2 subunit of the nAChR have shown that binding of nicotine to receptors containing this subunit is the first step in a pathway leading to increased dopamine levels in the mesolimbic dopamine system, and ultimately to the behavioral effects of nicotine in a test of nicotine reinforcement. Mice deficient in various alpha subunits of the nAChR will identify the partners of beta2 mediating the addictive properties of nicotine. In addition, more data needs to be gathered on the electrophysiological properties of different subunit combinations, the effects of nicotine on different neurotransmitter systems and the links between the molecular biology of nicotine receptors, their physiology and the ultimate role of individual receptor subtypes in complex behaviors. Multidisciplinary approaches to nAChR function will be essential to answering these questions. PMID- 11768169 TI - Imaging the neurochemistry of nicotine actions: studies with positron emission tomography. AB - Although the effects of nicotine in the brains of laboratory animals have been investigated extensively, very little is known about its effects in the human brain. With positron emission tomography (PET), a non-invasive imaging technology that allows measurement of the concentration of positron-labeled compounds that are of physiological and pharmacological relevance, it has become possible to investigate the effects of nicotine in the human brain. These imaging studies have shown that nicotine has very fast pharmacokinetics in the human brain, that it changes cerebral blood flow (CBF) and brain metabolism, and that at least some of these effects show acute tolerance. PET studies have also shown that, in addition to nicotine, cigarettes possess other pharmacological actions that may contribute to their reinforcing effects, that cigarettes inhibit monoamine oxidase (MAO) A and B in the brain, and that this inhibition recovers with cigarette discontinuation. Although the nicotine receptors have not yet been imaged in the living human brain, PET studies in the primate brain have shown very high concentration of receptors in the thalamus and a high rate of blockade by doses of nicotine that approximate plasma levels achieved by humans when smoking cigarettes. However, further studies are required to determine the levels of nicotine receptor occupancies achieved when smoking a cigarette and those required for the nicotine patch to be therapeutically effective, to measure the half-life for MAO inhibition by cigarettes and the mechanisms underlying this inhibition, and to evaluate the effects of smoking on nicotine receptors and on other neurotransmitter systems in the human brain. PMID- 11768170 TI - Vice President Al Gore. Plenary address at Addicted To Nicotine: A National Research Forum July 27-28, 1998, Bethesda, MD. PMID- 11768171 TI - Nicotine self-administration. AB - Any research pertaining to smoking or nicotine must demonstrate that its findings relate to changes in smoking or nicotine self-administration in order to be potentially relevant to understanding nicotine dependence or to treating smoking cessation. Nicotine alone, isolated from tobacco smoke, is self-administered by animals and humans. Pharmacological factors such as speed of dosing, dose amount, and pre-treatment with nicotinic antagonists clearly influence onset or rate of nicotine self-administration. However, environmental cues associated with nicotine intake can also substantially influence rate of self-administration and must be considered in the development of any treatment for smoking cessation. The specific acute subjective and behavioral effects of nicotine responsible for maintaining self-administration need to be identified, along with the minimum nicotine dose necessary for these effects. Individual differences in these effects, such as between men and women, also need to be examined. Findings in neuroscience and other areas of research need to be directly related to nicotine self-administration in order to clearly understand how they influence nicotine dependence. Overlooked by researchers is the influence of environmental factors, including social facilitation, on smoking or nicotine self-administration; these factors must be the primary cause of smoking relapse that occurs more than a week or so after a quit attempt. Laboratory-based findings must be extended to the natural environment to determine the degree to which they relate to smoking and nicotine reinforcement among smokers in the community (the population and venue for future treatment efforts). PMID- 11768172 TI - Behavioral and cognitive effects of smoking: relationship to nicotine addiction. AB - Nicotine addiction is an extremely complex process that involves biological, psychological, behavioral, and cultural factors. Three factors that influence smoking and that are influenced by smoking are performance, stress, and body weight. We know that if nicotine-addicted smokers are deprived of nicotine, attentional and cognitive abilities can be impaired, and such deficits can be reversed if the person smokes or is given nicotine. In nonsmokers and nondeprived smokers, nicotine enhances finger tapping, focused and sustained attention, recognition memory, and reasoning. Stress results in increased smoking, but there is little empirical evidence that smoking reduces stress. Stress reduction from smoking is likely the relief of withdrawal-induced negative mood that is experienced between cigarettes. Smokers weigh on average 3-4 kg less than nonsmokers, and the weight-gain seen after quitting smoking also averages 3-4 kg. Changes in eating and energy expenditure are responsible for the body weight changes seen during smoking cessation and relapse. We need to know the full range of conditions under which nicotine affects behavior. The mechanisms by which stress functions to maintain nicotine addiction are not well understood. We do not know what interventions are effective in addressing the stress experienced during smoking cessation. Because no effective interventions have been developed to prevent weight-gain after quitting, research should focus on the concern or perception of weight-gain. We need to understand how and why body weight concerns vary across gender, age, and ethnicity because of the implications for designing effective smoking-cessation programs. PMID- 11768173 TI - Comorbidity and smoking. AB - Several behavioral/psychological/psychiatric traits/disorders have been associated with increased initiation of smoking, nicotine dependence, and decreased cessation. Although much research has focused on psychiatric disorders, subclinical syndromes (e.g., minor depression and heavy drinking) probably influence smoking initiation and cessation more because they are so much more prevalent. In prospective studies, comorbidity predicts smoking and smoking predicts comorbidity. Preliminary evidence suggests several plausible mechanisms by which this two-way linkage could occur. In addition, other variables (e.g., genetics) could account for the comorbidity/smoking association. What we need to know: how strong and consistent are comorbidity/smoking associations? Is the association of smoking and comorbidity increasing over time? Are the hypothesized mechanisms for the association valid? Can treating comorbidity improve smoking cessation outcomes? Would applying the concept of comorbidity to psychosocial conditions (e.g., poverty) be helpful? PMID- 11768174 TI - Individual differences in smoking: gender and nicotine addiction. AB - Understanding individual differences in smoking behavior and nicotine dependence can increase knowledge of smoking dynamics and aid in the development of treatment regimens. Nicotine dependence among smokers is variable, and in some cases, fails to develop even after years of smoking. This variation can influence treatment outcome and presents a challenge to treatment developers. Gender differences are evident sometimes in smoking prevalence, in smoking cessation, and smoking rate. Gender, however, may be a superficial indicator; reasons for smoking, individual reactions to nicotine, and cultural sanctions and role definitions may be more influential. Analyses of individual differences should focus on identifying the underlying processes that control smoking behavior. PMID- 11768175 TI - The biology of nicotine dependence: from the 1988 Surgeon General's Report to the present and into the future. PMID- 11768176 TI - Psychological interventions: state of the art. AB - The usefulness of psychological interventions in smoking cessation is well established. Ongoing efforts are aimed at establishing interventions for specific diagnostic groups, developing interventions that are targeted at smokers who do not seek treatment, and combining psychological and pharmacological treatment. There is emerging evidence that useful treatments have been developed for smokers with a depression history, and that expert system interventions based upon a stage model can be useful in changing the smoking behavior of smokers who are not yet ready to quit. Psychological interventions add to the efficacy of nicotine replacement therapy, but whether they add to the efficacy of other pharmacotherapies is not known. There is a need to determine whether psychological interventions are useful for diagnostic groups other than depressive disorder, and if so, whether they need be specific for that group. Additional research is needed on interventions for smokers who are not ready to quit, both in developing new techniques, and determining the need and usefulness of adaptations of those in existence to specific populations. PMID- 11768177 TI - New medications for nicotine dependence treatment. AB - For several years, nicotine replacement therapy (nicotine gum, patches, and nasal spray) has been the mainstay for the treatment of nicotine dependence. The nicotine vapor inhaler is a new pharmacological adjunct shown to be effective in placebo-controlled trials. It delivers a vaporized form of nicotine to the oral mucosa. Bupropion sustained release (SR) is the first non-nicotine pharmacological treatment approved for smoking cessation and is thought to be effective because of its dopaminergic activity on the pleasure and reward pathways in the mesolimbic system and nucleus accumbens. Though few studies have been reported, there is pharmacological rationale to use combined pharmacotherapies for the treatment of nicotine dependence. While there are a limited number of reported studies with mixed findings using higher than the standard nicotine patch dose, use of higher doses of nicotine patch therapy (i.e., more than one patch at a time) may be appropriate for smokers who previously failed single dose patch therapy or in those whose nicotine withdrawal symptoms were not adequately relieved with standard therapy. The concept of therapeutic drug monitoring can be applied to nicotine replacement therapy. A new product, a sublingual nicotine tablet, has shown efficacy in a double-blind placebo-controlled trial and will likely be approved in the future. The anti hypertensive, mecamylamine, has been found to have efficacy for smoking cessation in a small trial. Nicotine and mecamylamine both occupy receptors that would otherwise be acted upon by nicotine from cigarettes, thus, when administered in combination, would be expected to occupy more receptors than either drug alone, thereby attenuating smoking reward and facilitating extinction of the smoking behavior. Pivotal trials of this combination are underway. Remaining questions include: (1) what is the optimal dose and duration of treatment using nicotine replacement therapy? (2) What is the optimal duration of treatment using bupropion? (3) What are the best combination treatments and which smokers are best suited for combination treatment? (4) Will other similar pharmacological agents with dopaminergic/noradrenergic activity have efficacy similar to bupropion? PMID- 11768178 TI - Combined behavioral and pharmacological treatments for smoking cessation. AB - Combined behavioral and pharmacological therapies appear to be the best approach for treating tobacco dependence. Because these therapies operate by different mechanisms, complementary and potentially additive effects may be expected. This paper focuses on nicotine replacement therapies (NRT) combined with supportive counseling because they are the most widely used and intensively researched treatment methods. Nicotine replacement medications and counseling appear to produce additive or less than additive effects when combined. Additive effects of combined therapies are generally apparent in the number of smokers who survive the first few weeks without smoking, but may disappear at longer-term follow-up. Because any smoking in the first two post-quit weeks is strongly associated with poor treatment outcome, reduced incidence of early smoking re-exposure appears to be important for improving long-term smoking cessation. Mechanisms underlying additive effects need further clarification. What are the independent and interactive roles of compliance with medication and with behavior change prescriptions, of pharmacological withdrawal suppression, of relapse prevention skills training, and of social support provided by counseling? Given the prevalence and importance of post-quit smoking relapses, can anything be done to further reduce incidence or to counteract their deleterious effects? Do any existing treatments slow relapse? If not, how can this be accomplished? Effective treatments now exist, but these cannot have an impact unless they are used; we need to know what methods can effectively enhance use. PMID- 11768179 TI - Primary care-based smoking interventions. AB - The primary care setting is an important place for promoting smoking cessation. Randomized clinical trials (RCTs) testing the effect of brief smoking interventions and comprehensive programs delivered in a primary care setting present excellent evidence that such interventions significantly increase patients' smoking cessation rates and that as the dose of intervention increases, the effect increases. Unfortunately, despite widespread dissemination of preventive services guidelines and positive physician attitudes towards such services, the current level of delivery of smoking cessation intervention by physicians in real-world settings is not high, making this a major research and public health concern. Interventions to increase the rate of implementation provider-delivered brief smoking interventions can be grouped broadly into: provider education; clinical systems and procedures (e.g., screening and tracking of patients); and organizational policy (e.g., reimbursement, coverage, performance measures). Given the significant effect that primary care-based interventions can have on smoking cessation, it is important to investigate methods to increase their rate of delivery and their effect. Examples of research to motivate to intervene questions include: what are the best incentives or combination of incentives for physicians? What are the most effective strategies to remind providers to intervene? How can each of these be best implemented in different types of settings and systems? How can a stepped-care and patient treatment matching model be used? The study of factors such as reimbursement policies and covered benefits do not lend themselves well to tightly-controlled randomized trials. Therefore, use of quasi-experimental designs, and application of qualitative strategies are needed. These designs represent a different challenge to the research community. PMID- 11768180 TI - Targeting treatments to special populations. AB - The average rate of long-term tobacco abstinence in a general population of treatment-seeking tobacco users is about 25%. Most of these treatments tend to use generic approaches, although the population of tobacco users is quite heterogeneous. It is entirely possible that special populations of smokers have specific treatment needs. If these needs are addressed, then treatment success may be augmented. This paper will review different issues that may surface when treating special populations. The special populations to be examined will be broken down by gender, age and route of tobacco administration. In addition, gaps in the scientific literature and directions for future research will be discussed. Once population-specific treatment needs are identified, then the effects of tailored treatments in augmenting treatment success can be determined. PMID- 11768181 TI - Interventions for treatment-resistant smokers. AB - We can understand resistance to treatment in smokers in two ways. First, when there is no awareness that smoking can be responsible for a physical disease, e.g., chronic obstructive lung disease or a dependence disorder. Second, when smokers actually seek treatment but fail to respond positively. The first kind resistance related to lack of awareness-may not be so common in adult US smokers, but is more common among young smokers. Information is crucial to increase awareness. However, such information must be presented in such a way that smokers respond to it. Whether a smoker takes action will also depend on what options and choices are available. Encouraging abrupt cessation as the only option is unlikely to motivate the smokers who have tried to quit many times and failed and those who do not want to give up completely. Alternatives such as quitting gradually-even harm-minimization-should be considered. Hopefully, taking some control over smoking with the help of, for example, nicotine replacement can increase self-efficacy and motivation to quit. For those who find it impossible to quit, harm-minimization procedures should definitely be invoked. PMID- 11768182 TI - Nicotine addiction: paradigms for research in the 21st century. PMID- 11768183 TI - Introductory notes on the tobacco problem. AB - Commercial tobacco products are the leading causes of preventable death, yet they are virtually unregulated. They are popular because they are effective nicotine delivery devices, and the most addictive product (the cigarette) is also the most likely to kill. PMID- 11768184 TI - Tobacco use as drug addiction: the scientific foundation. AB - Tobacco use is strongly driven by the pharmacological actions of nicotine in the central nervous system. This review will summarize some of the seminal research findings relating to nicotine dependence and will highlight fundamental questions that must yet be answered. The evidence that nicotine is an addictive drug was summarized in the 1988 Report of the Surgeon General which concluded that nicotine fulfills the criteria for a dependence-producing drug. More recently, research has further characterized the pharmacological effects of nicotine in the brain and elucidated the basic pathophysiology of nicotine addition. Moreover, research shows that nicotine replacement therapy, such as nicotine patch or gum, can prevent or reverse withdrawal symptoms. It is also clear that the form of nicotine delivery is a major determinant of addiction potential and that cigarettes and smokeless tobacco products are both highly engineered drug delivery devices that act not only to provide users with controllable doses of nicotine, but also to maximize the addictive effects of nicotine. Along with the understanding of the dependence process has come a rapidly expanding arsenal of treatment for the disorder. There are many major questions about the nature and course of nicotine addiction that remain unanswered and must be addressed if we are to continue to improve our ability to prevent tobacco dependence as well as to provide more effective and acceptable options for treatment and disease prevention in those who are already addicted. PMID- 11768185 TI - Ethnicity, gender and risk factors for smoking initiation: an overview. AB - Although the prevalence of cigarette smoking has increased dramatically among youth over the past several years, there are significant ethnic and gender differences in prevalence rates. This paper presents highlights of the research literature on ethnic and gender differences in risk factors for smoking. The effects of peer and family influences may vary by both ethnicity and gender. White youth, especially females, may be more susceptible to the negative influence of friends' smoking than are African-American youth. Although the evidence about the relative importance of parent smoking among ethnic groups is contradictory, recent data suggest that African-American parents provide stronger anti-smoking messages than do white parents. The subgroups also vary in their perceptions of the negative consequences of smoking, with Asian-American and African-American females perceiving stronger negative consequences. Cultural expectations may place white females at increased risk for smoking. The link between depressed mood and smoking also varies by subgroup. Finally, popular media figures may influence the appeal of smoking and be differentially relevant to youth subgroups. We need: (1) specific examinations of ethnic and gender effects with attention paid to identifying protective factors among certain ethnic/gender subgroups; (2) to know more about how family influences may vary by the ethnic/gender subgroups and over the developmental course of smoking; (3) to know more about how youth cope with negative moods and the role of smoking in coping; and (4) to investigate whether the factors that protect youth in some subgroups can be diffused to others. PMID- 11768186 TI - Child and adolescent psychopathology as risk factors for subsequent tobacco use. AB - A growing body of research suggests that a number of types of psychopathology that occur during childhood and adolescence are also associated with an increased risk for tobacco use. This paper assesses the relationship between several types of child and adolescent psychopathology and subsequent tobacco use. The types of psychopathology that are discussed include 'externalizing' disorders such as conduct problems and attention-deficit/hyperactivity disorder (ADHD), and 'internalizing' disorders such as depression and anxiety disorders. The strongest evidence for connections between child and adolescent psychopathology and subsequent tobacco use is for conduct problems, ADHD, and depression. There is much weaker support for a connection between anxiety disorders and tobacco use. The relationships between conduct problems and ADHD (which frequently co-occur) and subsequent tobacco use are quite robust. Possible explanations of the relationships between conduct problems, ADHD, and tobacco use are presented. There appears to be a bidirectional relationship between depression and tobacco use; i.e., each has a comparable probability of preceding the other. Areas of particular importance are: (a) the effects of various psychopathologies on various aspects of tobacco use; (b) the role of comorbid psychopathologies; (c) identification of protective factors; (d) the effects of moderators (e.g., gender, ethnicity); (e) mechanisms and processes ('active ingredients') associated with various psychopathologies; (f) implications for intervention; and (g) possible cohort effects. PMID- 11768187 TI - The genetic epidemiology of smoking. AB - The enormous personal and societal costs associated with tobacco are well documented. Unlike the large literature on the prevalence and consequences of tobacco use, there are fewer data on the genetic epidemiology (family, adoption, and twin studies) of tobacco use initiation and nicotine dependence. This review is limited to smoking as this has been the overwhelming focus of the literature. The data from family, adoption, and twin studies strongly support a substantial genetic influence on the initiation and maintenance of smoking. The literature supports the following hypothesis of the development of nicotine dependence. Smoking initiation is the obligatory first step. Liability to initiating smoking results from genetic influences (approximately 60%) and from environmental influences shared by members of a twin pair (approximately 20%) and that are specific to an individual (approximately 20%). The impact of shared environment may be particularly pronounced in mid-adolescence when many begin smoking. A subset of those who initiate smoking progress to nicotine dependence: genetic factors appear to be more prominent in this transition (approximately 70%) and shared environmental influences appear to be negligible. The genetic factors that predispose to smoking initiation appear to overlap substantially but not completely with those for nicotine dependence. The substantial impact of genetic factors on smoking behavior has engendered molecular genetic studies of this complex trait. We need to localize and identify the specific genes involved-which genes predispose to smoking initiation and which to nicotine dependence? If such genes are located, by what biological mechanisms do they operate? Do these genes act directly by altering or enhancing the pharmacokinetics or pharmacodynamics of nicotine? Do they act indirectly via personality or depression? Are these genes specific to nicotine or are they also involved in dependence on other licit and illicit psychoactive substances? Are there different mechanisms in men and women? What are the specific environmental factors and how do genes and environment interact? PMID- 11768188 TI - Nicotine metabolism variability and nicotine addiction. AB - Individual variation in nicotine metabolism may play a role in a person's level of smoking, as well as in the transition from initiation to maintenance of a smoking behavior pattern. Since there is a paucity of research on nicotine metabolism in youth that smoke, a brief review of salient aspects of nicotine metabolism in adults provides a basis from which to extrapolate. We do know that factors influencing the rate of nicotine metabolism include differences in nicotine intake and absorption, inhalation patterns, genetic polymorphisms of pertinent enzymes, as well as daily activities such as meal consumption. Variability is illustrated with differences in cotinine levels identified in African-American and Caucasian women and in menthol and nonmenthol smokers. There are a number of areas where more information to improve understanding the initiation and maintenance of smoking behavior is needed. Characterization of nicotine metabolism and smoking topography in youth from multiple ethnic groups who are engaged in smoking initiation is currently lacking. Important measures of smoke constituent exposure such as carbon monoxide, nicotine and cotinine, as well as puff volume and duration and respiratory movements should be addressed. While there are numerous factors that impact initiation and maintenance of smoking behavior, nicotine metabolism may represent one important aspect. PMID- 11768189 TI - A common genetic defect in nicotine metabolism decreases risk for dependence and lowers cigarette consumption. AB - Nicotine is the primary compound present in tobacco that is responsible for establishing and maintaining tobacco dependence; dependent smokers adjust their smoking behavior to maintain peripheral and central nicotine levels. CYP2A6 is the enzyme responsible for the majority of the inactivation of nicotine in humans. This enzyme is also responsible for activating tobacco-related procarcinogens such as the nitrosamines. This paper outlines how genetic variation in the CYP2A6 gene may protect individuals from becoming nicotine dependent smokers, and if dependent, how impairment of the CYP2A6 gene function decreases the number of cigarettes consumed by smokers (Pianezza M, Sellers EM, Tyndale RF. 1998. A common genetic defect in nicotine metabolism decreases smoking. Nature 393(6687):750). We also discuss recent findings which suggest that mimicking this gene defect by inhibiting CYP2A6 decreases nicotine metabolism and smoking. Further research is needed in order to improve our understanding of how genetic variation in CYP2A6 alters the risk for nicotine dependence and lowers nicotine consumption. This includes a better understanding of how the genetic variants alter nicotine metabolism in vivo in males and females as well as the role of CYP2A6 genetic variation in risk for tobacco related cancers. In addition we need to gain a better understanding of how manipulating this enzyme could be used therapeutically in prevention and treatment of smoking as well as in exposure reduction. PMID- 11768190 TI - Multiple risk factors for the initiation of smoking: the public health imperative for multidisciplinary genetic epidemiological investigations of nicotine addiction. PMID- 11768191 TI - The social costs of tobacco advertising and promotions. AB - Recent longitudinal evidence suggests that approximately 34% of all new tobacco experimentation occurs because of tobacco advertising and promotions. Based on this figure, in this paper we estimate the long-term impact on mortality and morbidity, as well as the economic and medical costs associated with smoking that is attributable to cigarette advertising and promotions in the United States. This study used several data sources, including the Teenage Attitudes and Practices Survey (TAPS), the 1993 and 1996 Adolescent California Tobacco Surveys (CTS), and the Food and Drug Administration's estimates of annual illness-related benefits of alternative effectiveness rates of banning tobacco advertising. Our resulting estimates are that in each year between 1988 and 1998, tobacco advertising and promotional activities generated approximately 193000 additional adult smokers who began smoking as adolescents because of advertisements and promotions. That decade of tobacco advertising and promotions will also result in approximately 46400 smoking-attributable deaths per year and 698400 years of potential life lost, which translates into costs of approximately $21.7 billion to $33.3 billion in total medical, productivity, and mortality-related costs. Even accounting for quitting behavior, each year of advertising-attributable smoking increases the number of smokers in the population. We conclude that annual costs can be expected to continue to increase if tobacco advertising and promotional activities are not effectively eliminated. If all tobacco industry advertising and promotional activities were banned for the next 25 years, nearly 60000 smoking-attributable deaths per year could be avoided, saving nearly 900000 life-years, $2.6 billion in excess medical expenses, and between $28 billion and $43 billion in mortality costs. PMID- 11768192 TI - Youth access to tobacco. AB - To start smoking, young people need a supply of tobacco products. Reducing youth access to tobacco is a new approach to preventing tobacco use that has been a focus of federal, state, and local tobacco control efforts over the past decade. All 50 states ban tobacco sales to minors, but compliance is poor because laws are not enforced. Consequently, young people have little trouble obtaining tobacco products. Commercial sources of tobacco (stores and vending machines) are important for underage smokers, who often purchase their own cigarettes. Underage youths also obtain tobacco from noncommercial sources such as friends, relatives, older adolescents, and adults. Educating retailers about tobacco sales laws has not produced long-term improvement in their compliance. Active enforcement of tobacco sales laws changes retailer behavior, but whether this reduces young people's access to tobacco or their tobacco use is not clear. The effectiveness of new local, state, and federal actions that aim to reduce youth access to tobacco remains to be determined. Can enforcing tobacco sales laws reduce young people's access to tobacco? If so, will this prevent or delay the onset of their tobacco use? How will youths' sources of tobacco change as commercial sources are restricted? What are the social (noncommercial) sources of tobacco for minors and how can youths' access to tobacco from these sources be reduced? What is the impact of the new federal policies aimed at reducing youth access to tobacco? Do new state and local laws that ban youth possession or use of tobacco have a net positive or negative impact on youth attitudes, access to tobacco, or tobacco use? What is the relative effectiveness and cost-effectiveness of efforts to reduce the supply of tobacco compared to those that aim to reduce demand for tobacco? Will either work alone or are both necessary to achieve reductions in youth smoking? PMID- 11768193 TI - Effective prevention programs for tobacco use. AB - Several types of prevention programs have shown effects on delaying or reducing youth tobacco use for periods of 1-5 years or more. These are referred to as evidence-based programs. However, they are not widely used. At the same time, with few exceptions, adolescent tobacco use rates have been stable or have increased in the 1990s. The challenge for prevention is to identify critical components shared by effective prevention programs--that is, components most associated with effect, and then to evaluate factors that are most likely to promote adoption, implementation, and diffusion of effective programs across schools and communities in the United States. Effective tobacco prevention programs focus on counteracting social influences on tobacco use, include either direct training of youth in resistance and assertiveness skills or, for policy and community organization interventions, direct or indirect (through adults) training in community activism, and are mainly theory-based, with an emphasis on three levels of theory: (a) personal (attitudes, normative expectations, and beliefs); (b) social (social or group behavior); and/or (c) environmental (communications and diffusion). Program effects increase with the use of booster sessions, standardized implementor training and support, multiple program components, and multiple levels of theory. Overall, multi-component community programs that have a school program as a basis, with supportive parent, media, and community organization components, have shown the most sustained effects on tobacco use. Positive program adoption by the school or community, extent and quality of program implementation, and existence of credible networks of leaders to promote the program are critical for any effect. Research on predictors of adoption, implementation, and diffusion of evidence-based programs is scanty relative to outcome research. In addition, more research is needed on why multi component programs appear to be most effective, whether effect is related to existing tobacco policies, whether prevention programs have differential effects on youth with different natural trajectories of tobacco use, and whether prevention programs can be used to recruit smokers into cessation programs. PMID- 11768194 TI - Dual X-ray absorptiometry and bone ultrasonography in patients with Rett syndrome. AB - This study evaluated bone status and bone turnover in 82 females (ages 2-21 years) with the Rett Syndrome (RS) and 82 age-matched controls. Bone mineral density (BMD) by dual X-ray absorptiometry (DXA) at the ultradistal and proximal radius and ultrasonographic (QUS) parameters at the calcaneus [speed of sound(SOS), broadband ultrasound attenuation(BUA), and stiffness] and at the phalanxes (amplitude dependent speed of sound: AD-SOS) were measured. We also measured serum calcium, phosphate, 25-hydroxyvitamin D, and biochemical markers of bone turnover. DXA and QUS parameters were significantly lower in patients with RS compared with controls and, among RS alone, in those treated with anticonvulsants and in those who are nonambulatory. Ambulatory RS patients showed QUS and DXA parameters significantly greater than nonambulatory patients but significantly lower than controls. Patients with RS treated with anticonvulsants presented QUS and DXA parameters lower than those of other RS. In RS patients, walking significantly influences BMD-UD, BMD-P, SOS. BUA. and Stiffness. Serum 25 hydroxyvitamin D was significantly lower in RS than in controls. These results suggest that ambulatory status, to a major extent, and anticonvulsant therapy certainly play an important role in the reduction of bone mass and bone quality, but they cannot completely explain the altered bone status. Whatever the cause, girls with RS present abnormal bone status with an increase in the risk of fracture. PMID- 11768195 TI - Vitamin D status of an outpatient clinic population. AB - Vitamin D insufficiency contributes to bone loss and fracture risk. Low 25 hydroxyvitamin D (25OHD) levels are common in elderly people and in housebound and hospitalized patients. This study was conducted to assess wintertime 25OHD levels in relation to self-reported vitamin D supplement use in an outpatient thyroid clinic population. We assessed the medical history, vitamin D intake from milk and supplements, and serum 25OHD levels in 231 women and 41 men who attended a Thyroid Clinic between January and March, 1999. Of the 272 outpatients, 13.6% had 25OHD levels <40 nmol/l and 53.3% had levels below 80 nmol/l. Fewer than 15% of the patients consumed more than 200 IU per day of vitamin D from milk. Vitamin D supplement use was a positive determinant of serum 25OHD concentration (P < 0.001). For example, among the largest homogenous subset of patients, Caucasian women (n = 137), 30% of the unsupplemented women, and 65% of those taking 400 lU/day of vitamin D had levels of 25OHD as high as 80 nmol/l. Other significant determinants of 25OHD levels were race, weight, milk intake, and recent southern travel. Thyroid disorder, serum TSH level, and age were not predictors of serum 25OHD concentration. In conclusion, at their current dietary vitamin D intake levels, most patients at this latitude will need vitamin D supplements in the wintertime. PMID- 11768196 TI - Qualitative and quantitative assessment of intratubular dentin formation in human natural carious lesions. AB - It was the aim of this study to investigate the scanning electron microscopy (SEM) features and the element content of calcium (Ca) phosphorus (P), magnesium (Mg), oxygen (O), and carbon (C) of sound dentin, demineralized dentin, secondary dentin, intratubular and peritubular de novo dentin formation due to caries progression and to compare the element content with chemically pure hydroxyapatite. Eighteen extracted teeth with deep dentin carious lesions were embedded in Technovit 9100 (Kulzer), and serial sections of 80 microm thickness were made. These sections were then investigated with polarized light microscopy to identify the lesions. Two sections of each lesion were then coated with carbon and studied with a scanning electron microscope. Of the 18 teeth, 8 showed intratubular dentin formation. The element content was measured using energy dispersive X-ray analysis (EDX). About 75% of all involved dentin tubules showed intratubular de novo dentin formation. The Ca/P ratio in sound dentin, demineralized dentin, peritubular dentin, and secondary dentin was within the range of hydroxyapatite, whereas in intratubular dentin the Ca/P ratio was different than that of hydroxyapatite. The element content for Ca was statistically highly significantly different (P < 0.01) among sound dentin/intratubular dentin, sound dentin/peritubular dentin, and sound dentin/ secondary dentin, but not between sound dentin/ demineralized dentin and sound dentin/hydroxyapatite. For the other measured elements varying statistical differences were found. Our results indicate that intratubular dentin does not occlude the dentin tubules completely and mineralizes different than that of sound dentin and may therefore not be true hydroxyapatite. PMID- 11768197 TI - Does combined gastrectomy and ovariectomy induce greater osteopenia in young female rats than gastrectomy alone? AB - Osteopenia develops in experimental animals following surgical removal of the ovaries (ovariectomy. Ovx) or the stomach (gastrectomy, Gx). Though the effect of Ovx has been ascribed to estrogen deficiency, the mechanism behind the Gx-evoked osteopenia remains unknown. In order to compare Gx- and Ovx-evoked osteopenia, young female rats were subjected to Ovx, gx, the combination of ovx and Gx, or sham operation (SHAM). Serum osteoclast-derived tartrate-resistant acid phosphatase 5b was measured as an index of bone resorption, and serum osteocalcin as an index of bone formation/turnover. Bone resorption predominated over bone formation during the first 4 days after Ovx but not later. Bone resorption predominated over bone formation throughout the first 4-week period after Gx. the changes were not additive in the ovx+Gx group. Transillumination and histomorphometry of the calvariae revealed extensive osteopenia in the Gx and the Ovx+Gx groups but not in the Ovx group. Peripheral quantitative computerized tomography of the femur metaphysis showed a decrease in the trabecular bone mineral density (BMD) in all three groups although Ovx+Gx seemed to induce greater trabecular bone loss than Gx alone. However, dual energy X-ray absorptiometry (DXA) of the intact femurs revealed reduced bone mineral content (BMC) in the Gx and Ovx+Gx groups but not in the Ovx group. Indeed, cortical bone was impaired by Gx and Ovx+Gx but not by Ovx. Hence, it seems clear that the Gx evoked osteopenia differs from that induced by Ovx but that the osteopenia induced by Ovx+Gx is only marginally greater than that induced by Gx alone. PMID- 11768198 TI - Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. AB - Two kinds of remodeling, stochastic and targeted, have been proposed based on the observation that microdamage in bone can initiate the remodeling process. Bisphosphonates are known to suppress stochastic bone remodeling. It has been hypothesized that bisphosphonates allow microdamage to accumulate, suggesting that they also suppress targeted remodeling. This study investigated whether suppression of remodeling using bisphosphonates inhibits remodeling targeted to repair microdamage, or whether the suppression of stochastic remodeling alone can account for the observed increase in damage accumulation. Beagle dogs were divided into three groups: control (CNT), risedronate-treated (RIS), and alendronate (ALN)-treated groups. The doses of both bisphosphonates were 6 times higher than the clinical doses. After 1-year treatment, animals were sacrificed and the right 9th rib was assigned to microdamage analysis. There were 3.06 times more associations between cracks and resorption spaces in CNT than expected (P < 0.005), indicating that remodeling normally targets cracks for repair, i.e., cracks can initiate a new remodeling event. However, although there was increased microdamage accumulation in RIS and ALN compared with CNT, fewer cracks than expected were associated with resorption spaces. The observation in RIS and ALN that there were fewer associations between cracks and resorption spaces than expected indicates that both targeted and non-targeted remodeling are suppressed in these groups. These data further suggest that the complete suppression of targeted remodeling could account for the increased microdamage burden. PMID- 11768199 TI - Trabecular domain factor and its influence on the strength of cancellous bone of the vertebral body. AB - The effects of architectural differences on the strength of cancellous bone of the vertebral body have not been clarified. This study was aimed at determining the influence of trabecular domain factor (TDF), a new histomorphometric parameter, on the maximum compressive strength (MCS) in vertebral cancellous bone. TDF is a variation coefficient representing the ratio dispersion of the area of each trabecula (Sd) to the area of its domain (D). A Voronoi diagram was used to determine trabecular domains. The materials comprised 35 lumbar vertebral bodies obtained at autopsy from 35 subjects aged 25-83 years. A mechanical test sample (12 x 12 x 16 mm) was cut out from each right half, and two large, undecalcified, horizontal sections from each left half. The fields (144 mm2 x 2) for image analyses were symmetrical with those for mechanical test samples in the other half of the same vertebral body. Bone volume (BV/TV), Sd, and D were semiautomatically measured. BV/TV correlated negatively with TDF (r = -0.73). Multiple regression analysis revealed the contributions of BV/TV (partial r = 0.75, p < 0.001) and TDF (partial r = -0.42, p < 0.02) to MCS. The model with BV/TV and TDF predicted MCS, 1.50 +0.15 BV/TV -0.03 TDF, more accurately (R2 = 0.83) than that with BV/TV alone (r2 = 0.79). We conclude that the bone volume primarily contributes to the MCS of vertebral cancellous bones but that the influence of TDF on the fragility becomes increasingly important as the bone volume decreases. PMID- 11768200 TI - Autocrine up-regulation of glucocorticoid receptors by interleukin-6 in human osteoblast-like cells. AB - Interleukin (IL)-6 is a bone-resorbing cytokine that acts primarily on osteoclast progenitors to stimulate both proliferation and differentiation. Glucocorticoids (GC) down-regulate IL-6 synthesis in different cell types, including osteoblasts. Given the fact that bone remodeling is a tightly controlled process, it is reasonable to think of auto-regulatory mechanisms in the bone microenvironment able to prevent excess IL-6 production. We have studied two human osteosarcoma cell lines (Saos-2 and MG-63) with different degrees of differentiation and different constitutive IL-6 production (3.4 +/- 0.2 (mean +/- SE) and 2,898 +/- 401 pg/10(6) cells, respectively). We measured the expression of glucocorticoid receptor (GR) in terms of specific binding sites after exposure of cells to different amounts of IL-6. Incubation for 20 hours with IL-6 at increasing concentrations up to 2,000 pg/ml yielded significant increase of GR binding sites in both cell lines. IL-6 was also able to revert the inhibitory effect of dexamethasone (1 microM) on GR in both cell lines. In MG-63 cells, that express higher concentrations of GR, IL-6 deprivation via a specific anti-IL-6 antibody (100 ng/ml) significantly decreased GR, as it was noticed, although to a lesser degree, using a specific anti-IL-6 receptor antibody. In Saos-2, cells that express lower concentrations of GR, a 40-hour treatment with human IL-1beta (10 ng/ml) significantly increased both IL-6 production and GR. This latter effect was completely abolished by co-treating the cells with the anti-IL-6 antibody. Our data are consistent with an autocrine up-regulation of GR expression by IL-6 in human osteoblast-like cells. This phenomenon, which is also relevant to paracrine cell-to-cell communication, subserves a feedback loop in the bone microenvironment that restrains excess inducible IL-6 production. In patients having high levels of IL-6 and given GCs, it could offer an additional explanation for the biphasic pattern of bone loss in the course of therapy. PMID- 11768201 TI - Statin given perorally to adult rats increases cancellous bone mass and compressive strength. AB - Recently, it has been shown that statins increased cancellous bone formation and volume in 3-month-old rats and induced a minor decrease in osteoclast number. In the present study, one-year-old female rats were given simvastatin (10 mg/kg) or placebo daily for 3 months by a gastric tube. Specimens, 2.0 mm high, were cut transversely from the 5th lumbar vertebral body. The cancellous bone core diameters within the cortical shell of each specimen were delineated by a micro CT scanner and then the cancellous bone was compressed in a materials testing machine between an upper and a lower platen with a diameter corresponding to the diameter of the cancellous bone core of each specimen. The cancellous bone volume was determined histomorphometrically on transverse sections. The cancellous bone volume in the simvastatin group (52.7 +/- 1.6%, mean value +/- SEM) was increased by 23% compared with the placebo group (42.8 +/- 1.7%). The compressive stress of the cancellous bone from the simvastatin group (31.8 +/- 2.7 MPa) was increased by 24% compared with the placebo group (24.1 +/- 1.9 MPa). No changes were found in cortical bone mass and strength after the statin treatment. In conclusion, statin given perorally to adult rats increased cancellous bone mass and increased cancellous bone compressive strength. The cancellous bone was found to possess normal biomechanical competence after the statin treatment. PMID- 11768203 TI - Genotypic variation in tetraploid wheat affecting homoeologous pairing in hybrids with Aegilops peregrina. AB - The Ph1 gene has long been considered the main factor responsible for the diploid like meiotic behavior of polyploid wheat. This dominant gene, located on the long arm of chromosome 5B (5BL), suppresses pairing of homoeologous chromosomes in polyploid wheat and in their hybrids with related species. Here we report on the discovery of genotypic variation among tetraploid wheats in the control of homoeologous pairing. Compared with the level of homoeologous pairing in hybrids between Aegilops peregrina and the bread wheat cultivar Chinese Spring (CS), significantly higher levels of homoeologous pairing were obtained in hybrids between Ae. peregrina and CS substitution lines in which chromosome 5B of CS was replaced by either 5B of Triticum turgidum ssp. dicoccoides line 09 (TTD09) or 5G of Triticum timopheevii ssp. timopheevii line 01 (TIMO1). Similarly, a higher level of homoeologous pairing was found in the hybrid between Ae. peregrina and a substitution line of CS in which chromosome arm 5BL of line TTD140 substituted for 5BL of CS. It appears that the observed effect on the level of pairing is exerted by chromosome arm 5BL of T turgidum ssp. dicoccoides, most probably by an allele of Ph1. Searching for variation in the control of homoeologous pairing among lines of wild tetraploid wheat, either T turgidum ssp. dicoccoides or T timopheevii ssp. armeniacum, showed that hybrids between Ae. peregrina and lines of these two wild wheats exhibited three different levels of homoeologous pairing: low, low intermediate, and high intermediate. The low-intermediate and high-intermediate genotypes may possess weak alleles of Ph1. The three different T turgidum ssp. dicoccoides pairing genotypes were collected from different geographical regions in Israel, indicating that this trait may have an adaptive value. The availability of allelic variation at the Ph1 locus may facilitate the mapping, tagging, and eventually the isolation of this important gene. PMID- 11768202 TI - Do different aminobisphosphonates have similar preventive effect on experimental thyroid hormone-induced osteopenia in rats? AB - We compared similar doses of three different aminobisphosphonates (BP): olpadronate (OPD), pamidronate (APD), and alendronate (ALE) on osteopenia induced by thyroxine (T4)-treatment in OVX and SHAM adult rats. Female Sprague Dawley rats (259 +/- 8 g) were treated with vehicle (SHAM+Vh and OVX+Vh), 250 microg T4/kg/day (SHAM+T4 and OVX+T4), 0.3 mg OPD/kg/day (SHAM+OPD and OVX+OPD), 0.2 mg ALE/kg/day (SHAM+ALE and OVX+ALE), 1.5 mg APD/kg/day (SHAM+APD and OVX+APD), T4+OPD (SHAM+T4+OPD and OVX+T4+OPD), T4+ALE (SHAM+T4+ALE and OVX+T4+ALE), and T4 +APD (SHAM+T4+APD and OVX+T4+APD) during a 5-week period. At the onset and at the end of the experiment, total skeleton bone mineral density (BMD) was assessed in vivo by DXA. Lumbar spine and proximal tibia BMDs were evaluated. T4 treatment to SHAM rats did not modify BGP levels significantly: neither did ovariectomy. T4 treatment to OVX rats significantly increased bone-gla-protein (BGP) levels compared with the other studied groups (P < 0.05). BP treatment reduced BGP levels to values significantly lower than SHAM rats (P < 0.05) and reduced bone alkaline phosphatase in SHAM groups (P < 0.05) but no changes were found in OVX groups. The increased D-Pyr excretion observed in SHAM+T4 rats (P = 0.056), OVX+Vh (P < 0.05), and OVX+T4 group (P < 0.001) compared with the SHAM+Vh rats was prevented by the BP treatment. OVX+Vh rats had total skeleton and proximal tibia BMD, and OVX+T4 group had total skeleton, spine, and proximal tibia BMD significantly lower than the SHAM+Vh group. BP treatment was also found to prevent this reduction. The reduced bone resorption and the prevention of bone loss showed no differences among very close, potentially equivalent doses of the three aminoBPs used. Consequently, treatment with very close similar doses of APD, ODP, and ALE prevented bone resorption and bone changes with the same efficacy. PMID- 11768204 TI - Cytology, RAPD, and seed colour of progeny plants from Brassica rapa-alboglabra aneuploids and development of monosomic addition lines. AB - Progeny plants from Brassica rapa-alboglabra aneuploids were characterized genetically by scoring random amplified polymorphic DNA (RAPD) markers and seed colour and cytologically as to chromosome number and pairing. Sets of RAPD markers specific for each of the encountered eight alien Brassica alboglabra chromosomes were defined. The finding of subsets of markers associated with the presence or absence of alien chromosomes inferred the frequent occurrence of intergenomic genetic recombination and introgression. The chromosome numbers were in the range 2n = 20-28, with a maximum of seven alien B. alboglabra chromosomes and one trisomic B. rapa chromosome. Five types of monosomic addition lines were obtained, two of which have not been developed before. Differences in chromatin condensation patterns made it possible to differentiate between the B. rapa and B. alboglabra chromosomes at diakinesis, and to detect intergenomic homoeological pairing. In addition to the frequent formation of trivalents by homoeologous pairing of an alien B. alboglabra chromosome and a background B. rapa pair, occasional heteromorphic intergenomic bivalents and B. rapa univalents were encountered. Homoeological intergenomic pairing occurred between chromosomes with similar centromeric and karyotypic positions. Plants with structurally changed alien chromosomes were found. The RAPD and cytological data substantiated each other. Observations of the colour of sown and harvested seeds indicated that B. alboglabra chromosome 4 carries a gene for brown seed colour. It exerts its control embryonically, and thus it differs from chromosome 1 which controls seed colour maternally. PMID- 11768205 TI - Evidence that the N-terminal extension of the vicieae convicilin genes evolved by intragenic duplications and trinucleotide expansions. AB - This study was aimed to identify lentil (Lens culinaris subsp. culinaris) convicilin genes and to carry out a comparative analysis of these genes in the tribe Vicieae. Convicilins differ from vicilins, a related group of plant seed storage proteins, mainly by the presence of an additional sequence of amino acids in the sequence corresponding to the first exon, referred as the N-terminal extension. A single gene for convicilin, a component of legume seed storage proteins, was identified in the cultivated lentil. In this species, the N terminal extension is formed by a stretch of 126 amino acids of which 59.2% are charged amino acids: 29.6% glutamic acid, 3.2% aspartic acid, 14.4% arginine, 8.8% lysine, and 3.2% histidine. This lentil convicilin sequence is similar to the sequence of convicilins in other species of the tribe Vicieae. However, the size of the N-terminal extension clearly differs among convicilins. Sequence comparison and phylogenetic analyses including convicilin and vicilin of Vicieae species indicated that the differentiation between vicilins and convicilins predated the differentiation of the two vicilin gene families (47- and 50-kDa vicilins), and that the N-terminal extension evolved mainly by a series of duplications of short internal sequences and triplet expansions, the predominant one being GAA. PMID- 11768206 TI - Construction of a YAC library from barley cultivar Franka and identification of YAC-derived markers linked to the Rh2 gene conferring resistance to scald (Rhynchosporium secalis). AB - The Rh2 resistance gene of barley (Hordeum vulgare) confers resistance against the scald pathogen (Rhynchosporium secalis). A high-resolution genetic map of the Rh2 region on chromosome I (7H) was established by the use of molecular markers. Tightly linked markers from this region were used to screen existing and a newly constructed yeast artificial chromosome (YAC) library of barley cv. Franka composed of 45,000 clones representing approximately two genome equivalents. Corresponding YAC clones were identified for most markers, indicating that the combined YAC library has good representation of the barley genome. The contiguous sets of YAC clones with the most tightly linked molecular markers represent entry points for map-based cloning of this resistance gene. PMID- 11768207 TI - Dinucleotide microsatellites from Eucalyptus sieberi: inheritance, diversity, and improved scoring of single-base differences. AB - Eight dinucleotide microsatellites were developed in Eucalyptus sieberi L. Johnson (silvertop ash), a member of the subgenus Eucalyptus. Transfer of six of these to the subgenus Symphyomyrtus and their Mendelian inheritance are demonstrated using a full-sib cross in Eucalyptus nitens. Genetic diversity parameters are presented for the eight loci based on a sample of 100 old-growth E. sieberi trees from a single natural stand. One locus, Es266, had an atypically high fixation index, and significantly deviated from Hardy-Weinberg equilibrium genotypic proportions, indicating the likely presence of null alleles. Two of the loci, Es076 and Es140, had many alleles that differed in size by only a single base pair, possibly because of short poly(A) or poly(T) stretches in their flanking regions. These two loci were by far the most polymorphic, but were difficult to score reliably on a capillary DNA sequencer. Reliability of scoring of these two one-base microsatellite loci was markedly improved by the incorporation of internal reference alleles into each sample analysed. PMID- 11768208 TI - Mapping genetic factors affecting the reaction to Xanthomonas axonopodis pv. phaseoli in Phaseolus vulgaris L. under field conditions. AB - The objectives of the present study were to evaluate the field effects of Xanthomonas axonopodis pv. phaseoli (Xap), which causes common bacterial blight (CBB) on common bean (Phaseolus vulgaris L.), and to identify genetic factors for resistance to CBB using a linkage map constructed with random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), simple sequence repeat (SSR), and amplified fragment length polymorphism (AFLP) markers. One hundred and forty-two F2:4 lines, derived from a cross between 'OAC Seaforth' and 'OAC 95-4', and the parents were evaluated for their field reaction to CBB. In the inoculated plots, the reaction to CBB was negatively correlated with seed yield, days to maturity, plant height, hypocotyl diameter, pods per plant, and harvest index. A reduction in seed yield and its components was observed when disease-free and CBB-inoculated plots were compared. The broad-sense heritability estimate of the reaction to CBB was 0.74. The disease segregation ratio was not significantly different from the expected segregation ratio for a single locus in an F2 generation. The major gene for CBB resistance was localized on linkage group (LG) G5. A simple interval mapping procedure identified three genomic regions associated with the reaction to CBB. One quantitative trait loci (QTL), each on LG G2 (BNG71Dra1), G3 (BNG21EcoRV), and G5 (PHVPVPK-1) explained 36.3%, 10.2%, and 42.2% of the phenotypic variation for the reaction to CBB, respectively. Together, these loci explained 68.4% of the phenotypic variation. The relative positions of these QTL on the core common bean map and their comparison with the previous QTL for CBB resistance are discussed. PMID- 11768209 TI - Physical mapping of resistant and susceptible soybean genomes near the soybean cyst nematode resistance gene Rhg4. AB - The soybean cyst nematode (SCN), Heterodera glycines Ichinohe, is the foremost pest of soybean (Glycine max L. Merr.). The rhg1 allele on linkage group (LG) G and the Rhg4 allele on LG A2 are important in conditioning resistance. Markers closely linked to the Rhg4 locus were used previously to screen a library of bacterial artificial chromosome (BAC) clones from susceptible 'Williams 82' and identified a single 150-kb BAC, Gm_ISb001_056_G02 (56G2). End-sequenced subclones positioned onto a restriction map provided landmarks for identifying the corresponding region from a BAC library from accession PI 437654 with broad resistance to SCN. Seventy-three PI 437654 BACs were assigned to contigs based upon HindIII restriction fragment profiles. Four contigs represented the PI 437654 counterpart of the 'Williams 82' BAC, with PCR assays connecting these contigs. Some of the markers on the PI 437654 contigs are separated by a greater physical distance than in the 'Williams 82' BAC and some primers amplify bands from BACs in the mid-portion of the connected PI 437654 BAC contigs that are not amplified from the 'Williams 82' BAC. These observations suggest that there is an insertion in the PI 437654 genome relative to the 'Williams 82' genome in the Rhg4 region. PMID- 11768210 TI - Polymorphism of PCR-based markers targeting exons, introns, promoter regions, and SSRs in maize and introns and repeat sequences in oat. AB - Sequence databases could be efficiently exploited for development of DNA markers if it were known which gene regions reveal the most polymorphism when amplified by PCR. We developed PCR primer pairs that target specific regions of previously sequenced genes from Avena and Zea species. Primers were targeted to amplify 40 introns, 24 exons, and 23 promoter regions within 54 maize genes. We surveyed 48 maize inbred lines (previously assayed for simple-sequence repeat (SSR) polymorphism) for amplification-product polymorphism. We also developed primers to target 14 SSRs and 12 introns within 18 Avena genes, and surveyed 22 hexaploid oat cultivars and 2 diploid Avena species for amplification-product polymorphism. In maize, 67% of promoter markers, 58% of intron markers, and 13% of exon markers exhibited amplification-product polymorphisms. Among polymorphic primer pairs in maize, genotype diversity was highest for SSR markers (0.60) followed by intron markers (0.46), exon markers (0.42), and promoter markers (0.28). Among all Avena genotypes, 64% of SSR markers and 58% of intron markers revealed polymorphisms, but among the cultivars only, 21% of SSR markers and 50% of intron markers were polymorphic. Polymorphic-sequence-tagged sites for plant-breeding applications can be created easily by targeting noncoding gene regions. PMID- 11768211 TI - Identification of a major gene and RAPD markers for yellow seed coat colour in Brassica napus. AB - The development of yellow-seeded Brassica napus for improving the canola-meal quality characteristics of lower fibre content and higher protein content has been restricted because no yellow-seeded forms of B. napus exist, and their conventional development requires interspecific introgression of yellow seed coat colour genes from related species. A doubled-haploid (DH) population derived from the F1 generation of the cross 'Apollo' (black-seeded) x YN90-1016 (yellow seeded) B. napus was analysed via bulked segregant analysis to identify molecular markers associated with the yellow-seed trait in B. napus for future implementation in marker-assisted breeding. A single major gene (pigment 1) flanked by eight RAPD markers was identified co-segregating with the yellow seed coat colour trait in the population. This gene explained over 72% of the phenotypic variation in seed coat colour. Further analysis of the yellow-seeded portion of this DH population revealed two additional genes favouring 'Apollo' alleles, explaining 11 and 8.5%, respectively, of the yellow seed coat colour variation. The data suggested that there is a dominant, epistatic interaction between the pigment I locus and the two additional genes. The potential of the markers to be implemented in plant breeding for the yellow-seed trait in B. napus is discussed. PMID- 11768212 TI - Expression, mapping, and genetic variability of Brassica napus disease resistance gene analogues. AB - Numerous sequences analogous to resistance (R) genes exist in plant genomes and could be involved in resistance traits. The aim of this study was to identify a large number of Brassica napus sequences related to R genes and also to test the adequacy of specific PCR-based tools for studying them. Different consensus primers were compared for their efficiency in amplifying resistance-gene analogues (RGAs) related to the nucleotide-binding-site subgroup of R genes. Specific primers were subsequently designed to fine-study the different RGAs and we tested their efficiency in three species related to B. napus: Brassica oleracea, Brassica rapa, and Arabidopsis thaliana. Forty-four B. napus RGAs were identified. Among 29 examined, at least one-third were expressed. Eighteen RGAs were mapped on 10 of the 19 B. napus linkage groups. The high variability within these sequences permitted discrimination of each genotype within a B. napus collection. The RGA-specific primers amplified RGAs in the B. oleracea and B. rapa genomes, but the sequences appear to be poorly conserved in A. thaliana. Specific RGA primers are a precise tool for studying known-sequence RGAs. These sequences represent interesting markers that could be correlated with resistance traits in B. napus or related Brassica genomes. PMID- 11768213 TI - TAFII70 protein in Cajal bodies of the amphibian germinal vesicle. AB - The localization of the TATA-binding protein (TBP) associated factor II70 (TAFII70) in the germinal vesicle (GV) of newt oocytes was investigated. In spreads of GV content, anti-hTAFII70 monoclonal antibody (mAb) stained Cajal bodies (CBs) that were either attached to specific sites on the lampbrush chromosomes or free in the nucleoplasm. To confirm this localization the PwTAFII70 cDNA was cloned and myc-tagged transcripts injected into the oocyte cytoplasm. Newly translated PwTAFII70 protein was detected a few hours later in the Cajal bodies. These data support the hypothesis that Cajal bodies are the assembly sites of the transcription machinery of the oocyte nucleus. TAFII70 protein can play a role in lampbrush transcription; alternatively TAFII70 can be considered a component in the subset of TFIID complexes that do not function during oogenesis, but are accumulated in the oocyte for later use during early development. PMID- 11768214 TI - A bacterial artificial chromosome (BAC) library of Malus floribunda 821 and contig construction for positional cloning of the apple scab resistance gene Vf. AB - The apple scab resistance gene Vf, originating from the wild species Malus floribunda 821, has been incorporated into a wide variety of apple cultivars through a classical breeding program. With the aim of isolating the Vf gene, a bacterial artificial chromosome (BAC) library consisting of 31 584 clones has been constructed from M. floribunda 821. From the analysis of 88 randomly selected BAC clones, the average insert size is estimated at 125 kb. If it is assumed that the genome size of M. floribunda 821 is 769 Mb/haploid, the library represents about 5x haploid genome equivalents. This provides a 99% probability of finding any specific sequence from this library. PCR-based screening of the library has been carried out using eight random genomic sequence-characterized amplified regions (SCARs), chloroplast- and mitochondria-specific SCARs, and 13 high-density Vf-linked SCAR markers. An average of five positive BAC clones per random SCAR has been obtained, whereas less than 1% of BAC clones are derived from the chloroplast or mitochondrial genomes. Most BAC clones identified with Vf linked SCAR markers are physically linked. Three BAC contigs along the Vf region have been obtained by assembling physically linked BAC clones based on their fingerprints. The overlapping relatedness of BAC clones has been further confirmed by cytogenetic mapping using fiber fluorescence in situ hybridization (fiber-FISH). The M. floribunda 821 BAC library provides a valuable genetic resource not only for map-based cloning of the Vf gene, but also for finding many other important genes for improving the cultivated apple. PMID- 11768215 TI - Heterofertilization exhibited by trifluralin-induced bicellular pollen on diploid and tetraploid maize crosses. AB - The heterofertilization rates and fertility of trifluralin-induced bicellular pollen were investigated in maize (Zea mays L.). A diploid inbred line, Oh43 (r1/r1), and a tetraploid line, Q28-1 (r1/r1/r1/r1), were pollinated with a trifluralin treated diploid stock heterozygous for R1-scm2. The gene R1-scm2 conditions purple pigmentation in both the embryo and the aleurone layer. Heterofertilized kernels were detected as discordant kernels, i.e., yellow kernel with purple embryo or purple kernel with white embryo. The diploid-diploid crosses treated with 0.2-0.3% Trefanocide solution (0.09-0.13% trifluralin) resulted in incidences of discordant kernels (3.7-4.8%) that were significantly higher than the control (2.3%). Most of the seedlings (86%) of the discordant kernels in the 0.3% treatment were triploids or triploid-class aneuploids. In tetraploid-diploid crosses, trifluralin treatments increased the number of plump kernels on the tetraploid ears. In the 0.3% treatment, 5.2% of ovaries produced plump kernels on the ears and most of the seedlings (92%) were tetraploids or tetraploid-class aneuploids, whereas in the control, only 1.5% ovaries produced plump kernels and most of the seedlings (98%) were triploids or triploid-class aneuploids. A high rate of discordance was observed among the plump kernels both in the treated plots (36.1-48.0%) and in the control (33.3%). Consequently, almost all of the plump kernels from the tetraploid-diploid crosses were considered to be the results of heterofertilization. PMID- 11768216 TI - Introgression of rye chromatin on chromosome 2D in the Portuguese wheat landrace 'Barbela.'. AB - The old Portuguese wheat landrace aggregate known as 'Barbela' shows good productivity under the low-fertility conditions often associated with acid soils. The use of genomic rye DNA, in combination with 45S rDNA and the repetitive sequences dpTal and pScl 19.2 as probes, in two sequential in situ hybridization steps enabled the identification of all chromosomes in the 'Barbela' wheat lines and the detection of the introgression of rye-origin chromatin onto wheat chromosome arm 2DL in two of the lines. Amplification of microsatellite loci using published primer pairs showed that the distal segment of wheat chromosome 2DL, which was involved in the rye translocation, was deleted. The identification and characterization of small recombinant chromosome segments in wheat-rye lines may allow their use in plant breeding programmes. Their presence in farmer maintained material demonstrates the importance of maintaining, characterizing, and collecting landrace material before valuable genetic combinations are lost as uniform commercial crops are introduced. PMID- 11768217 TI - Molecular characterization of a Thinopyrum intermedium group 2 chromosome (2Ai-2) conferring resistance to barley yellow dwarf virus. AB - The wheat--Thinopyrum intermedium addition lines Z1 and Z2 carry 21 pairs of wheat chromosomes and one pair of Th. intermedium chromosomes (2Ai-2) conferring resistance to barley yellow dwarf virus (BYDV). GISH results using the genomic DNA of Pseudoroegneria strigosa (S genome) as the probe indicated that the 2Ai-2 chromosome in Z1 and Z2 is an S-J intercalary translocation. Most of the 2Ai-2 chromosome belongs to the S genome, except for about one third in the middle region of the long arm that belongs to the J genome. The results of detailed RFLP analyses confirmed that the 2Ai-2 chromosome is extensively homoeologous to wheat group 2 chromosomes. Some new RFLP markers specific to the 2Ai-2 chromosome were identified. A RAPD marker, OP-R16(340), specific to the 2Ai-2 chromosome, was screened. We converted the RAPD marker into a sequence-characterized amplified region (SCAR) marker (designated SC-R16). The study establishes the basis for selecting translocation lines with small segments of the 2Ai-2 chromosome and localizing the BYDV resistance gene when introgressed into a wheat background. PMID- 11768218 TI - Rapid and reliable identification of rice genomes by RFLP analysis of PCR amplified Adh genes. AB - The rice genus (Oryza L.) consists of 24 species with 10 recognized genome types. With the realization of many useful genes in species of wild rice, continuous efforts have been made to understand their genomic composition and relationships. However, the identification of rice genomes has often been difficult owing to complex morphological variation and formation of allotetraploids. Here we propose a rapid and reliable method for identifying rice genomes based on the restriction sites of PCR-amplified Adh genes. The experimental procedure was as follows: (i) amplify a portion of Adh1 and Adh2 genes with the locus-specific PCR primers; (ii) digest PCR products with restriction enzymes that distinguish different genomes; and (iii) run the digested products on 1.4% agarose gel, and photograph. Using various combinations of restriction digestion of the two Adh genes, all of the rice genomes can be identified. PMID- 11768219 TI - Synaptonemal complex analysis in spermatocytes and oocytes of turbot, Scophthalmus maximus (Pisces, Scophthalmidae). AB - A surface-spreading synaptonemal complex (SC) technique was used to analyze spermatocytes and oocytes of turbot (Scophthalmus maximus) to visualize the process of chromosome synapsis. The total SC length was 205 +/- 12 microm in males and 172 +/- 29 microm in the only female analyzed. A representative SC karyotype of turbot was obtained. Each SC showed lateral elements of equal length. No bivalent exhibiting atypical synaptic behaviour that could be associated with heteromorphic sex chromosomes was observed, either in males or in the female. The DNA content of turbot was evaluated in eight individuals of both sexes by flow cytometry analysis. The 2C mean DNA content of turbot (1.308 +/- 0.009 pg/cell) was among the lowest observed within fishes. No statistical differences in DNA content were revealed between the sexes [Wilcoxon/Mann-Whitney test; P(W(x) = 0.243)]. The SC/DNA content ratio observed in turbot was the highest reported to date in bony fishes (Osteichthyes). PMID- 11768220 TI - Intra-species DNA polymorphism in the tobacco cyst-nematode complex (Globodera tabacum) using AFLP. AB - Amplified fragment length polymorphism (AFLP) was used to obtain information on the within-species genetic variability of the tobacco cyst-nematode (TCN) complex. AFLP was found to be well suited to this type of study. The current classification of TCN was confirmed. Results indicate that the Globodera tabacum solanacearum group, believed to be restricted to the U.S.A., also occurs in Mexico. The within-species variability of TCN is considerable. Populations from Mexico may form a new subgroup. AFLP group-specific markers were identified for two of the TCN subgroups: Globodera tabacum tabacum and Globodera tabacum solanacearum. PMID- 11768221 TI - Polymorphisms flanking the mariner integration sites in the rice gall midge (Orseolia oryzae Wood-Mason) genome are biotype-specific. AB - In an effort to study genome diversity within and between the Indian biotypes of the Asian rice gall midge, Orseolia oryzae, a major insect pest of rice, we made use of mariner transposable element integration site polymorphisms. Using degenerate primers, the design of which is based on mariner sequences, we amplified a ca. 450 bp mariner sequence from the rice gall midge. The mariner sequence showed homology with that of a mariner element isolated from the Hessian fly, Mayetiola destructor, a major dipteran pest of wheat. Southern hybridization, using this mariner fragment as a probe, revealed that the mariner elements are moderately to highly repetitive in the rice gall midge genome. Based on the sequence information of this 450-bp PCR-amplified fragment, outward directed primers were designed and used in an inverse PCR (iPCR) to amplify the DNA flanking the conserved regions. To study the regions flanking the mariner integration sites, we employed a novel PCR-based approach: a combination of sequence specific amplification polymorphism (SSAP) and amplified fragment length polymorphism (AFLP). The outward-directed mariner-specific primer was used in combination with adapter-specific primers with 1-3 selective nucleotides at their 3' ends. The amplification products were resolved on an agarose gel, Southern transferred onto nylon membranes, and probed with the iPCR fragment. Results revealed biotype-specific polymorphisms in the regions flanking the mariner integration sites, suggesting that mariner elements in the rice gall midge may be fixed in a biotype-specific manner. The implications of these results are discussed in the context of biotype differentiation. PMID- 11768222 TI - The pericentromeric heterochromatin of the grass Zingeria biebersteiniana (2n = 4) is composed of Zbcen1-type tandem repeats that are intermingled with accumulated dispersedly organized sequences. AB - DNA reassociation and hydroxyapatite chromatography were used to isolate high copy DNA of the grass Zingeria biebersteiniana (2n = 4). In situ hybridization demonstrated that the DNA isolated was enriched for pericentromere-specific repetitive sequences. One abundant pericentromere-specific component is the differentially methylated tandem-repeat family Zbcen1. Other sequences isolated, Zb46 and Zb47A, are dispersed and display similarity to parts of the gypsy- and copia-like retrotransposable elements of other grasses. In situ hybridization with the copia-like sequence Zb47A resulted in dispersed labelling along the chromosome arms, with a significant signal accumulation in the pericentromeric region of all chromosomes. It is concluded that the pericentromeric heterochromatin of Z. biebersteiniana is composed of members of the Zbcen1 tandem repeat family and that these tandem arrays are intermingled with accumulated putative copia-like retrotransposon sequences. An observed Rab1 interphase orientation suggests that the length of the chromosomes rather than the genome size is the determining factor of the Rab1 phenomenon. PMID- 11768223 TI - Construction of a linkage map of the Rennell Island Tall coconut type (Cocos nucifera L.) and QTL analysis for yield characters. AB - AFLP and SSR DNA markers were used to construct a linkage map in the coconut (Cocos nucifera L.; 2n = 32) type Rennell Island Tall (RIT). A total of 227 markers were arranged into 16 linkage groups. The total genome length corresponded to 1971 cM for the RIT map, with 5-23 markers per linkage group. QTL analysis for yield characters in two consecutive sampling periods identified nine loci. Three and two QTLs were detected for number of bunches and one and three QTLs for number of nuts. The correlation of trait values between characters and evaluation periods is partially reflected in identical QTLs. The QTLs represent characters that are important in coconut breeding. The cosegregation of markers with these QTLs provides an opportunity for marker-assisted selection in coconut breeding programmes. PMID- 11768224 TI - Influence of genetic background and heterozygosity on meiotic recombination in Arabidopsis thaliana. AB - Plant breeding relies on genetic variability generated by meiotic recombination. Control of recombination frequencies is not yet possible, but would significantly extend the options for plant-breeding strategies. A prerequisite would be variability of recombination frequencies. In this study, 15 transgenic kanamycin (KR) and hygromycin (HR) resistance gene insertions mapping to the five Arabidopsis thaliana chromosomes were used as genetic markers. Recombination frequencies were determined from the frequencies of resistance phenotypes within populations segregating for linked KR and HR markers. Recombination frequencies of marker pairs were compared among these four ecotypes, among F1s in both reciprocal forms derived from these ecotypes, and between F1s and their parent lines. On average, the recombination frequencies in F1 crosses were substantially higher (up to 2-fold) than in the homozygous parental ecotypes. A strong negative correlation between genetic similarities of ecotypes and recombination frequencies was detected for two adjacent marker pairs located on the long arm of chromosome 3, but not for marker pairs in other genomic regions. Our results suggest that heterozygosity influences recombination in plant breeding, and cannot be ignored in genetic mapping of genomes. PMID- 11768225 TI - The detection, cloning, and characterisation of WIS 2-1A retrotransposon-like sequences in Triticum aestivum L. and xTriticosecale Wittmack and an examination of their evolution in related Triticeae. AB - Retrotransposons and other mobile elements are major components of the repeated DNA fraction in higher-plant genomes. They have undoubtedly played an important role in higher plant genome evolution. The present work details the detection and characterisation of a WIS 2-1A related sequence in direct wheat relatives, and discusses the prevalence and evolution of its copy number in their genomes. An increase in copy number is detected when following the natural hybridisation processes that gave rise to bread and durum wheats. However, the opposite is observed in the development of triticale, a synthetic hybrid. PMID- 11768226 TI - Alpha-catulin maps to the familial dysautonomia region on 9q31. AB - Familial dysautonomia is a severe autosomal-recessive neurodegenerative disease that primarily affects the Ashkenazi Jewish population. We present the mapping of alpha-catulin and show that it maps precisely to the familial dysautonomia candidate region on 9q31. Patient sequence analysis identified two new sequence variants, which show linkage disequilibrium with this disease. A G to A transition at nucleotide 423 in exon 3 is a silent base change that does not alter the Val residue at position 141. A G to C transversion at nucleotide 1579 changes the Glu at postion 527 to Gln. These base changes were analyzed in several patients, unaffected Ashkenazi Jewish controls, and non-Jewish controls. Because of the presence of these sequence variants in several unaffected individuals, alpha-catulin is unlikely to be the causative gene in this disease. PMID- 11768227 TI - Genetic diversity in Bambara groundnut (Vigna subterranea L.) germplasm revealed by RAPD markers. AB - Random amplified polymorphic DNA (RAPD) markers were used to assess genetic diversity in Bambara groundnut (Vigna subterranea L.) germplasm using 25 African accessions from the collection in the International Institute for Tropical Agriculture, Ibadan, Nigeria. Fifty random decamer primers were screened to assess their ability to detect polymorphism in bambara; 17 of them were selected for this study. Considerable genetic diversity was found among the V. subterranea accessions studied. The relationships among the 25 accessions were studied by cluster analysis. The dendrograms showed two main groups of accessions mainly along the lines of their geographic origin. It is concluded that RAPD can be used for germplasm classification in bambara groundnut and hence for improving this crop. PMID- 11768228 TI - 2001 Award of Excellence winner. DR. Michael Hayden. PMID- 11768229 TI - 2001 Young Scientist Award winner. Dr. Thomas Hudson. PMID- 11768230 TI - Vascular response of the rabbit bladder to chronic partial outlet obstruction. AB - Partial outlet obstruction of the rabbit urinary bladder results, initially, in a rapid increase in bladder mass and remodeling of the bladder wall. Previously, it was shown that this response was characterized by serosal growth (thickening) which was apparent after 1 day of obstruction, before any visible vascularization was observed. After 1 week of obstruction, significant microvessel formation was seen in the transition region between the detrusor smooth muscle and the thickening serosa; after 2 weeks the entire serosa was vascularized. In this study we investigated the effect of chronic (4 week) partial outlet obstruction on microvessel density and distribution in the bladder wall immunohistochemically using CD31 as a marker for vascular endothelium. Transverse sections of bladder wall were examined after 4 weeks of no surgery, sham surgery or partial obstruction. The microvessel density of the obstructed rabbit bladder mucosa and detrusor smooth muscle increased relative to augmentation of these compartments while new vessels appeared in the thickening serosa. Although vessel density did not change with obstruction a significant shift in mean vessel circumference to the left occurred indicating a significant increase in the number of microvessels and small vessels consistent with angiogenesis. PMID- 11768231 TI - Aryl hydrocarbon receptor/dioxin receptor in human monocytes and macrophages. AB - Aryl hydrocarbon receptor (AhR) belongs to the bHLH/PAS transcription factor family and is activated by various polycyclic or halogenated aromatic hydrocarbons, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3 methylcholanthrene (3MC). In the present study, we showed that in U937 cells and human macrophages AhR, with its partner cofactor Arnt, is expressed and CYP1A1 mRNA expression is induced in the presence of AhR ligand 3MC. Moreover, we showed that AhR, associating with Arnt, binds to target DNA sequences and activates transcription. Since part of AhR is activated into DNA binding species in the absence of exogenous ligand and competitive AhR antagonist alpha-naphthoflavone inhibits this activation process with reducing CYP1A1 mRNA expression levels, the presence of endogenous ligand is indicated. PMID- 11768232 TI - Concomitant accumulation of intracellular free calcium and arachidonic acid in the ischemic-reperfused rat heart. AB - This study was designed to elucidate the relationship between enhanced cytoplasmic calcium levels (Ca2+i) and membrane phospholipid degradation, a key step in the loss of cellular integrity during cardiac ischemia/reperfusion induced damage. Isolated rat hearts were subjected to 15 min ischemia followed by 30 min reperfusion. Ca2+i was estimated by the Indo-1 fluorescence ratio technique. Degradation of membrane phospholipids as indicated by the increase of tissue arachidonic acid content was assessed in tissue samples taken from the myocardium at various points of the ischemia/reperfusion period. The hemodynamic parameters showed almost complete recovery during reperfusion. Fluorescence ratio increased significantly during ischemia, but showed a considerable heart-to-heart variation during reperfusion. Based upon the type of change of fluorescence ratio during reperfusion, the hearts were allotted to two separate subgroups. Normalization of fluorescence ratio was associated with low post-ischemic arachidonic acid levels. In contrast, elevated fluorescence ratio coincided with enhanced arachidonic acid levels. This observation is suggestive for a relationship between the Ca2+-related fluorescence ratio and arachidonic acid accumulation probably due to a calcium-mediated stimulation of phospholipase A2. PMID- 11768233 TI - Molecular cloning and functional characterization of the canine androgen receptor. AB - Sex steroids, including testosterone, play a major role in determining peak bone mass in mammals and the subsequent loss of total bone mass with advancing age. Testosterone, and its active metabolite dihydrotestosterone (DHT), bind with high affinity to the androgen receptor (AR), a member of the nuclear hormone receptor superfamily. These receptors function as transcription factors, binding together with accessory proteins to specific DNA response elements in the promoters of androgen responsive genes. To further characterize AR function in a model species of relevance to bone and pharmaceutical research, we cloned a partial canine AR from a canine kidney cDNA library and then cloned the remaining 5' segment by PCR from canine ventral prostate cDNA. The complete sequence obtained was 3577 bp. This sequence contained a single open reading frame of 2721 bp, potentially encoding a protein of 907 amino acids with a predicted molecular weight of 98.7 kD. Sequence analysis of the protein encoded by this open reading frame reveals that the modular domains providing the DNA binding and ligand binding functions are identical to those reported for eight other mammalian ARs. Northern analysis of poly-A+ RNA from ventral prostate revealed three very low abundance transcripts of approximately 9 kb and RT-PCR analysis showed relatively high expression of AR in canine ventral prostate, testis, and kidney, with lower levels detectable in spleen, skeletal muscle, heart, and liver. Competition binding studies using 3H-DHT as ligand demonstrated specific displacement by DHT, testosterone, and the anabolic steroid stanozolol, with IC50 values of 1.3, 2.5 and 3.8 nM, respectively. Binding of DHT also resulted in the stimulation of an androgen responsive-luciferase reporter following cotransfection with the canine AR into 293 cells. Immunohistochemistry using an antibody directed to the C terminal 19 amino acids of the human AR showed strong staining of the secretory epithelial cells in canine ventral prostate. Together, these data indicate that we have cloned the canine AR and that its functional DNA binding and ligand binding domains are absolutely conserved with those reported for eight other species. PMID- 11768234 TI - Tolerance of isolated rat hearts to low-flow ischemia and hypoxia of increasing duration: protective role of down-regulation and ATP during ischemia. AB - We tested the hypothesis that down-regulated hearts, as observed during low-flow ischemia, adapt better to low O2 supply than non-down-regulated, or hypoxic, hearts. To address the link between down-regulation and endogenous ischemic protection, we compared myocardial tolerance to ischemia and hypoxia of increasing duration. To that end, we exposed buffer-perfused rat hearts to either low-flow ischemia or hypoxia (same O2 shortage) for 20, 40 or 60 min (n = 8/group), followed by reperfusion or reoxygenation (20 min, full O2 supply). At the end of the O2 shortage, the rate-pressure product was less in ischemic than hypoxic hearts (p < 0.0001). The recovery of the rate-pressure product after reperfusion or reoxygenation was not different for t = 20 min, but was better in ischemic than hypoxic hearts for t = 40 and 60 min (p < 0.02 and p < 0.0002, respectively). The end-diastolic pressure remained unchanged during low-flow ischemia (0.024 +/- 0.013 mmHg x min(-1)), but increased significantly during hypoxia (0.334 +/- 0.079 mmHg x min(-1)). We conclude that, while the duration of hypoxia progressively impaired the rate-pressure product and the end-diastolic pressure, hearts were insensitive of the duration of low-flow ischemia, thereby providing evidence that myocardial down-regulation protects hearts from injury. Excessive ATP catabolism during ischemia in non-down-regulated hearts impaired myocardial recovery regardless of vascular, blood-related and neuro-hormonal factors. These observations support the view that protection is mediated by the maintenance of the ATP pool. PMID- 11768236 TI - Chemomodulation of carcinogen metabolising enzymes, antioxidant profiles and skin and forestomach papillomagenesis by Spirulina platensis. AB - Numerous reports have revealed an inverse association between consumption of some selective natural products and risk of developing cancer. In the present study the effect of 250 and 500 mg/kg body wt. of Spirulina was examined on drug metabolising phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 7-week-old Swiss albino mice. The implications of these biochemical alterations have been further evaluated adopting the protocol of benzo(a)pyrene induced forestomach and 7,12 dimethylbenz(a)anthracene (DMBA) initiated and croton oil promoted skin papillomagenesis. Our primary findings reveal the 'Monofunctional' nature of Spirulina as deduced from its potential to induce only the phase II enzyme activities associated mainly with carcinogen detoxification. The glutathione S transferase and DT-diaphorase specific activities were induced in hepatic and all the extrahepatic organs examined (lung, kidney and forestomach) by Spirulina pretreatment (significance level being from p < 0.05 to p < 0.005) except for the low dose treatment in forestomach. With reference to antioxidant enzymes viz., superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione were increased significantly by both the chosen doses of Spirulina from p < 0.01 to p < 0.005. Chemopreventive response was quantitated by the average number of papillomas per effective mouse (tumor burden) as well as percentage of tumor bearing animals. There was a significant inhibition of tumor burden as well as tumor incidence in both the tumor model systems studied. In the skin tumor studies tumor burden was reduced from 4.86 to 1.20 and 1.15 by the low and high dose treatment respectively. In stomach tumor studies tumor burden was 2.05 and 1.73 by the low and high doses of Spirulina treatment against 3.73 that of control. PMID- 11768235 TI - Induction of heme oxygenase-1 by phenylarsine oxide. Studies in cultured primary liver cells. AB - Heme oxygenase-1, the major inducible isoform of heme oxygenase (HO), can be induced by heme and numerous other physical and chemical factors, many of which cause cellular 'stress'. This has led to the realization that HO-1 is a major highly conserved stress or heat shock protein. Recent work has implicated activation of mitogen-activated protein kinases and other kinases in the mechanism of induction of HO-1, and suggested that signal transduction pathways through tyrosine kinases are involved in induction of HO-1 gene expression by stress inducers. We hypothesized that phenylarsine oxide (PAO), an inhibitor of protein tyrosine phosphatases (PTPs), might up-regulate the HO-1 gene. Here, we show that a remarkably brief (1-15 min) exposure of normal hepatocytes to low concentrations (0.5-3 microM) of PAO produces a marked increase in mRNA and protein of HO-1. This increase is comparable to the level obtained by addition of heme (20 microM), and occurs without producing changes in cellular glutathione levels or stabilization of HO-1 message. Preincubation of cells with inhibitors of protein synthesis decreased the ability of PAO to increase levels of HO-1 mRNA, suggesting that the inductive effect requires de novo protein synthesis. Addition of thiol donors abrogated the PAO-mediated induction of HO-1 in a dose dependent fashion. Addition of genistein, a tyrosine kinase inhibitor, blunted the induction produced by both PAO and heme. After brief incubations with PAO or heme, cell extracts showed comparable increases in levels of protein tyrosine phosphorylation in general, and specifically in ZAP70 kinase. Our results are consistent with the proposition that induction of HO-1 by PAO involves inhibition of specific PTP(s), and that the mechanisms of induction of HO-1 by PAO and by heme may share some common pathways. PMID- 11768237 TI - Effect of dietary ghee--the anhydrous milk fat on lymphocytes in rats. AB - Lymphocytes are important components of the immune system. Dietary lipids affect the functioning of the immune system. Changes in the lipid composition of the lymphocyte membrane is a case in point. Membrane structural changes are reflected in the altered function of the cell. Lymphocyte proliferation and lymphocyte rosetting are membrane associated phenomena. Ghee, is a clarified butter product, commonly used in the Indian diet. It is rich in saturated fatty acids and also contain oxysterols which are generated on prolonged heating of ghee. Male weanling rats were fed 2.5% (of the total fat levels) of fresh or thermally oxidized ghee for a period of 8 weeks. The control rats were fed groundnut oil. Lipid composition of lymphocytes in ghee fed rats showed changes. In vitro lipid peroxidation of lymphocyte membranes increased by 26% in oxidized ghee fed rats. Na+K+ ATPase activity was decreased in oxidized ghee fed rats (18%). Lymphocyte proliferation was reduced in ghee fed rats (32%), compared to the controls, irrespective of the mitogens used (Con-A or PHA), or the tissue (splenocytes or peripheral blood lymphocytes). Oxysterols present in oxidized ghee are the likely agents inhibiting lymphoproliferation. Rosetting of lymphocytes decreased in the fresh ghee fed rats by 16% and in oxidized ghee fed rats by 25%. Membrane fluidity declined in the oxidized ghee fed rats. It is concluded that feeding ghee results in decreased proliferation of lymphocytes. Also, feeding oxidised ghee results in decreased proliferation of lymphocytes through alterations in the structure of the lymphocyte membranes in the rat. PMID- 11768238 TI - Distribution of Fhit protein in rat tissues and its intracellular localization. AB - The FHIT (fragile histidine triad) gene located at chromosome 3p14.2 has been proposed as a candidate tumor suppressor gene in human cancers. Fhit protein with the diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) hydrolase activity is the protein product of FHIT gene. The way in which Fhit exerts its tumor suppressor activity and the relationship of the Ap3A hydrolase activity to tumor suppression are not known. As a step toward understanding of the Fhit function in the cell we have explored its intracellular localization and distribution in the rat tissues. Data obtained from immunoblot analysis showed that Fhit protein was most abundant in spleen and brain. Moderate amount of Fhit was detected in kidney and liver, whereas the level of Fhit protein in heart, skeletal muscle and kidney glomeruli was undetectable. RT-PCR performed on RNA isolated from these tissues showed no product, whereas the level of Fhit mRNA in spleen, brain, kidney, liver and lung correlated with the Fhit protein level. The immunoblot analysis performed on subcellular fractions of various rat tissues obtained by differential and density gradient centrifugation showed that Fhit protein was localized exclusively in nucleus and at the plasma membrane. Presented data showing nuclear and plasma membrane localization of Fhit may support the hypothesis concerning Fhit as a signaling molecule. PMID- 11768239 TI - Ets-1 is involved in transcriptional regulation of the chick inducible nitric oxide synthase gene in embryonic ventricular myocytes. AB - In order to elucidate roles of Ets family of transcription factors in transcriptional activation of inducible nitric oxide synthase (iNOS) genes, we analyzed the chick iNOS gene expression in cultured chick embryonic ventricular myocytes (CEVM). Deletional analysis and site-directed mutagenesis demonstrated that both the Ets/PEA3 site (-221 to -216 bp) and the kappaB site (-101 to -93 bp) of the 5'-flanking region of the chick iNOS gene were involved in the maximal activation of the lipopolysaccharide (LPS)-induced expression of the reporter (luciferase) gene, although the proximal kappaB site played the more essential role. Electrophoretic mobility shift assay revealed that LPS augmented the nuclear protein bindings to the Ets/PEA3 as well as kappaB motifs. Ets-1, one of the Ets proteins, was suggested to be bound to the Ets/PEA3 oligonucleotide. By Northern blot analysis, LPS was shown to induce iNOS mRNA in CEVM, along with a preceding increase in the levels of c-ets-1 mRNA. Ets-1 may be involved in the iNOS gene transcription in CEVM, presumably through interacting with the NF kappaB. PMID- 11768240 TI - Potential mechanism of fibronectin deposits in acute renal failure induced by mercuric chloride. AB - Many glomerular diseases are associated with changes in the expression and distribution in the components of extracellular matrix. A remarkable feature in acute renal failure induced by mercuric chloride in rats was large fibronectin (Fn) deposits in kidneys 1 h post-HgCl2 injection (5 mg/kg body wt., s.c.). Our study examined some mechanisms as potential explanation of the early Fn deposits in mercuric chloride induced acute renal failure. Total tissue mRNA of livers and kidneys of control and treated rats were used in Northern blot to determine whether accumulation of Fn in kidney is associated with increases in the expression of this protein in the kidney and/or in the liver. Analysis of Fn levels by Western blot were also performed. Northern blot did not show significant difference between control and treated rats, while the abundance of polymerized-Fn in kidney tissue was increased 1 h and 5 h post HgCl2 injection. HgCl2 influence on Fn folding was studied in vitro to detect possible conformational changes that could altered its normal pattern of matrix assembly and/or binding to different ligands. In this context HgCl2 binding to Fn was measured following native tryptophan fluorescence of Fn in the presence of HgCl2 (0.5-250 mM). Binding parameters for the HgCl2-Fn complex formation were Kd = (1.6 +/- 0.2) 10(-4) M; n = 1 +/- 0.3, indicating a low apparent affinity and one type binding site. Thermal denaturation of Fn showed, between 30-60 degrees C, a soft reversible conformational change, while between 75-80 degrees C a highly and irreversible transition is produced suggesting a modification of the tertiary structure. HgCl2 abolished this transition. The kinetic of thermal unfolding of Fn was also measured and the effects observed due to HgCl2 presence reinforced the previous data. Finally, the effect of HgCl2 on Fn binding to denatured collagen (gelatin) was also measured as an index of the effect of this cation on biological properties of Fn. Fn binds gelatin strongest in the presence of HgCl2. Our results suggest that higher Fn deposits in kidney-treated rats seems not to be associated to augmented mRNA-Fn neither in kidney nor in liver. On the other hand, increased levels of polymerized Fn abundance was observed in kidney tissue from mercury-treated rats. We also describe that HgCl2 promotes, in vitro, conformational changes on Fn structure, inducing its denaturation and increasing its binding to gelatin, all events that could be related to the Fn deposits in renal tissues of HgCl2 treated rats, and could be expected in other situations that promoted interstitial fibrosis, not associated to overexpression of matrix proteins. PMID- 11768241 TI - Effects of D-mannoheptulose upon D-glucose metabolism in tumoral pancreatic islet cells. AB - D-[3H]mannoheptulose was recently reported to be poorly taken up by tumoral pancreatic islet cells of the RINm5F and INS-1 lines. We have now investigated the effects of D-mannoheptulose upon D-glucose metabolism in these two cell lines. D-mannoheptulose (1.0-10.0 mM) only caused a minor decrease of D-glucose metabolism in RINm5F cells, whether at low (1.1 mM) or higher (8.3 mM) D-glucose concentration. A comparable situation was found in INS-1 cells examined after more than 20 passages. In both cases, however, the hexaacetate ester of D mannoheptulose (5.0 mM) efficiently inhibited D-glucose metabolism. In the INS-1 cells, the relative extent of the inhibitory action of D-mannoheptulose upon D glucose metabolism increased from 12.4 +/- 2.6 to 38.3 +/- 3.8% as the number of passages was decreased from more than 20 to 13-15 passages, the latter percentage remaining lower, however, than that recorded in INS-I cells also examined after 13-15 passages but exposed to D-mannoheptulose hexaacetate (66.9 +/- 2.2%). These findings when compared to our recent measurements of D-[3H]mannoheptulose uptake, reinforce the view that the entry of the heptose into cells and, hence, its inhibitory action on D-glucose metabolism are dictated by expression of the GLUT2 gene. PMID- 11768242 TI - Angiotensin II induced cardiac hypertrophy in vivo is inhibited by cyclosporin A in adult rats. AB - Recently, the calcium-calmodulin-dependent calcineurin pathway has been defined as a central pathway for the induction of cardiac hypertrophy. The purpose of this study was to determine if cardiac hypertrophy in animals chronically treated with angiotensin II (AngII), could be prevented by blocking this pathway with cyclosporin A (CsA). Female Wistar rats were treated with AngII by subcutaneous infusion and injected twice a day with CsA (25 mg/kg) for 7 days. In the AngII treated group there was a 30% increase in the heart/body weight ratio (p < 0.05 vs. control). The increase in heart weight was blocked with CsA. Substantial increases in ANF and betaMHC gene expression were detected in the AngII treated animals, which were either attenuated or blocked with CsA treatment. Thus, this study demonstrates that CsA does prevent the development of cardiac hypertrophy in AngII treated rats, suggesting that the calcium-calmodulin-dependent calcineurin pathway is associated with angiotensin II induced hypertrophy in vivo. PMID- 11768243 TI - Plant catechols prevent lipid peroxidation in human plasma and erythrocytes. AB - The antioxidant activity of several plant catechol derivatives was tested in buffer, plasma, and human erythrocytes. In buffer, chlorogenic acid (CGA), caffeic acid (CA), and dihydrocaffeic acid (DCA) reduced ferric iron equally well in the ferric reducing antioxidant power (FRAP) assay. Low concentrations of the polyphenols enhanced the ability of plasma to reduce ferric iron by about 10%. In plasma, lipid hydroperoxide and F2-isoprostane formation induced by a water soluble free radical initiator were reduced by CGA at concentrations as low as 20 microM. During incubation at 37 degrees C, human erythrocytes took up DCA, but not CGA, and intracellular DCA enhanced the ability of erythrocytes to reduce extracellular ferricyanide. When intact erythrocytes were exposed to oxidant stress generated by liposomes containing small amounts of lipid hydroperoxides, extracellular CGA at a concentration of 5 microM decreased both lipid peroxidation in the liposomes, and spared alpha-tocopherol in erythrocyte membranes. These results suggest that the catechol structure of these compounds convey the antioxidant effect in plasma and in erythrocytes. PMID- 11768244 TI - Bcl-2/Bax protein expression in heart, slow-twitch and fast-twitch muscles in young rats growing under chronic hypoxia conditions. AB - We have studied the magnitude of apoptosis in heart, slow-twitch skeletal muscle (soleus) and fast-twitch skeletal muscle (gastrocnemius) of rats exposed to 3 weeks in vivo chronic hypoxia. Apoptosis was evaluated biochemically by DNA laddering and by TUNEL and annexin V-staining. The expression of Bax and Bcl-2 proteins was determined by immunohistochemistry and Western blotting. Western blot analysis revealed only a slight difference in Bax expression among the different tissues under normoxic and hypoxic conditions; therefore we can consider that Bax protein is constitutively expressed in muscle tissues. However a singular pattern of Bcl-2 expression was observed among the different tissues under normoxic conditions. Bcl-2 protein was more expressed in fast-twitch glycolytic muscles than in slow-twitch or oxidative muscles with a highest value found in gastrocnemius (4926 +/- 280 AU), followed by soleus (2138 +/- 200 AU) and a very low expression was displayed in the heart muscle (543 +/- 50 AU). After exposure to hypoxia for 21 days (10% O2), Bcl-2 protein expression markedly increased, (44%) in gastrocnemius, (323%) in soleus and (1178%) in heart, with significant differences (p < 0.05 student t-test), reaching a similar threshold of expression in both types of muscles. Furthermore, no sign of apoptosis was detected by TUNEL assay, annexin V-binding assay or DNA electrophoresis analysis. The latter suggested some indiscriminate fragmentations of DNA without apoptosis. In conclusion, we postulate that these protein modifications could represent a adaptative mechanism allowing a better protection against the lack of oxygen in oxidative muscles by preventing apoptosis. PMID- 11768245 TI - Insulin-like effects of a physiologic concentration of carnitine on cardiac metabolism. AB - Pharmacologic (millimolar) levels of carnitine have been reported to increase myocardial glucose oxidation, but whether physiologically relevant concentrations of carnitine affect cardiac metabolism is not known. We employed the isolated, perfused rat heart to compare the effects of physiologic levels of carnitine (50 microM) and insulin (75 mU/l [0.5 nM]) on the following metabolic processes: (1) glycolysis (release of 3H2O from 5-3H-glucose); (2) oxidation of glucose and pyruvate (production of 14CO2 from U-14C-glucose, 1-14C-glucose, 3,4-14C-glucose, 1-14C-pyruvate, and 2-14C-pyruvate); and (3) oxidation of palmitate (release of 3H2O from 9,10-3H-palmitate). We found that addition of carnitine (50 microM) to a perfusate containing both glucose (10 mM) and palmitate (0.5 mM) stimulated glycolytic flux by 20%, nearly doubled the rate of glucose oxidation, and inhibited palmitate oxidation by 20%. These actions of carnitine were uniformly similar to those of insulin. When carnitine and insulin were administered together, their effects on the oxidation of glucose and palmitate, but not on glycolysis, were additive. When pyruvate (1 mM) was substituted for glucose, neither carnitine nor insulin influenced the rate of oxidation of pyruvate or palmitate. In combination, however, carnitine and insulin sharply suppressed pyruvate oxidation (75%) and doubled the rate of palmitate oxidation. None of the responses to carnitine or insulin was affected by varying the isotopic labeling of glucose or pyruvate. The results show that carnitine, at normal blood levels, exerts insulin-like effects on myocardial fuel utilization. They also suggest that plasma carnitine in vivo may interact with insulin both additively and permissively on the metabolism of carbohydrates and fatty acids. PMID- 11768246 TI - Small bowel review: diseases of the small intestine. AB - In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practicing gastroenterologist. Selected important clinical learning points include the following: (1) glutamine may restore the AIDs-associated increased intestinal permeability to normal; (2) substance P is a major mediator of diarrhea caused by Costridium difficile toxin A, acting by binding to a G protein-coupled receptor, and represents a possible 2therapeutic target; (3) the serological diagnosis of celiac disease has been greatly enhanced with the use of anti-endomysial antibody testing, and the recent antitransglutaminase; (4) a quarter of patients with celiac disease may have secondary pancreatic insufficiency and require enzyme replacement therapy; (5) in the patient with unexplained elevation in the serum transaminase concentration, consider celiac disease as an obscure possibility; (6) bosentan and endothelin receptor agonist may prove to be useful in reducing gut ischemia in patients with septic shock; and (7) the administration of recombinant human fibroblast growth factor-2 may prove to be useful to prevent radiation damage to the gastrointestinal tract. PMID- 11768247 TI - Small bowel review: normal physiology part 1. AB - In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand. PMID- 11768249 TI - BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation. AB - Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) 1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region. PMID- 11768250 TI - Control of irritable bowel syndrome with polyamine analogs: a structure-activity study. AB - The evaluation of a group of polyamine analogs as agents to ameliorate diarrhea predominant irritable bowel syndrome is described. Each compound was assessed when administered subcutaneously in a psychological stress-induced model of irritable bowel syndrome in rodents for its ability to reduce stool output in a dose-dependent manner. The spermine pharmacophore is shown to be an excellent platform from which to construct compounds to treat irritable bowel syndrome. The activity of the compounds is very dependent on both the nature of the terminal alkyl groups and the geometry of the methylene spacers separating the nitrogens. In addition to the subcutaneous studies, several compounds, N1,N11 diethylnorspermine, N1,N12-diethylspermine, N1,N12-diisopropylspermine, N1,N14 diethylhomospermine, N,N'-bis[5-(ethylamino)pentyl]-1,4-butanediamine, N,N'-bis[2 (4-piperidinyl)ethyl]-1,4-diaminobutane, and N,N'-bis[3-(ethylamino)propyl]-trans 1,4-cyclohexanediamine, were subsequently evaluated for oral efficacy. The remarkable activity of N,N'-bis[3-(ethylamino)propyl]-trans-1,4 cyclohexanediamine underscores the need to explore this framework further as a pharmacophore for the construction of other analogues to relieve the symptoms of diarrhea-predominant IBS. PMID- 11768251 TI - Spectrum of autoantibodies in celiac patients and relatives. AB - The coexistence of celiac disease together with a range of autoimmune disorders has already been reported. The aims of this study were to perform a broad spectrum of autoantibodies in celiac patients (N = 56), their first-degree relatives (N = 118), and compare the data with healthy controls (N = 101) and patients with inflammatory bowel disease (N = 42; Crohn's disease, N = 18 and ulcerative colitis, N = 24). All serum samples were tested by indirect immunofluorescence to the anti-endomysium antibodies (EmA), anti-neutrophil cytoplasmic (ANCA), anti-smooth-muscle (SMA), anti-mitochondrial (AMA), anti nuclear (ANA), anti-liver-kidney microsomal (LKM), anti-gastric parietal cells (GPCA), and anti-thyroid microsome (TMA). EmA were detected in 100% of celiac patients ingesting gluten and in 16.1% of the first-degree relatives, while ANCA were positive only in patients with ulcerative colitis (45.6%) and Crohn's disease (16.5%). Fourteen CD patients (25%) were positive for at least one of the other autoantibodies, with significant prevalence of TMA, ANA, and GPCA, while the relatives showed 17.8% of positivity, with an increased prevalence of ANA and TMA. These results emphasize the value of screening for different autoantibodies in celiac patients and their relatives and corroborate the need for evaluation and follow-up of these individuals. PMID- 11768248 TI - Small bowel review: normal physiology part 2. AB - In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) numerous peptides are being identified which stimulate the proliferation and functional response of the small intestine to disease or resection, and may in time find a clinical use; (2) under usual in vivo conditions, absorption of nutrients has little effect on the paracellular movement of water; (3) the permeability of the intestine is modified by the function of the tight junctions, and measuring intestinal permeability may be useful to reflect the presence of disease; (4) the release of serotonin is influenced by cholinergic, adrenergic, and nonadrenergic, noncholinergic mechanisms, and serotonin agonists and antagonists may play an important future role in the treatment of motility disorders; (5) the use of endothelin receptor antagonists may be useful for the treatment of intestinal anaphylaxis; (6) the alterations in intestinal pH and motility in patients with Crohn's disease may influence the action of pH- or time-dependent release medications; and (7) patients with irritable bowel syndrome may also have abnormalities in gastric and small intestinal motility. PMID- 11768252 TI - Clinical and subclinical autoimmune thyroid disease in adult celiac disease. AB - Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance. PMID- 11768253 TI - Effect of octreotide on small intestinal motility in HIV-infected patients with chronic refractory diarrhea. AB - Octreotide has been used to treat HIV-associated diarrhea. We aimed to assess the effect of octreotide on small intestinal motility in a group of HIV infected individuals with chronic diarrhea. Small intestinal motility was measured continuously for 48 hr by ambulatory strain gauge manometry in 12 HIV seropositive subjects with chronic diarrhea. During the second 24-hr period, intravenous octreotide was administered (100 microg every 8 hr). Postprandial and nocturnal fasting motility data were compared before and during administration of octreotide. Octreotide was associated with increased numbers of migrating motor complexes (MMCs) (7.25 vs 4.92, P = 0.03), and a relative decrease in the duration of phase II (22% vs 49.8, P = 0.03) during nocturnal fasting activity. Postprandial activity was absent in half of the subjects and the duration significantly reduced in the remainder. In conclusion, octreotide has a significant effect on small intestinal motility in HIV-infected individuals with diarrhea, which may influence intestinal transit. PMID- 11768255 TI - Effect of peritoneal dialysis on gastric myoelectrical activity in patients with chronic renal failure. AB - Impaired gastric myoelectrical activity has been reported in patients with chronic renal failure (CRF). The effect of peritoneal dialysis on this function has not previously been described. The aim here was to investigate the effect of peritoneal dialysis on gastric myoelectrical activity. Gastric myoelectrical activity was recorded by electrogastrography (EGG) in 23 patients with CRF (18 with dyspepsia) during peritoneal dialysis and with the peritoneal cavity empty of dialysis fluid (14 patients), and in 20 healthy controls. Two 30-min EGG recordings before and after a solid test meal were analyzed using spectral analysis methods. No significant difference in the percentage of normal 2- to 4 cpm slow waves was found in patients on peritoneal dialysis compared to those with the peritoneal cavity empty of dialysis fluid or to controls (in fasting state 83 +/- 3%, 80 +/- 5% and 89 +/- 4%, in fed state 91 +/- 3%, 86 +/- 4% and 83 +/- 4%, respectively). It was found that the power ratio (change in power of normal slow waves in fed state) was significantly higher in the 14 patients on peritoneal dialysis compared to the same patients with the peritoneal cavity empty of dialysis fluid (27.2 +/- 10.7 vs 8.6 +/- 4.8, P < 0.05). There was no significant difference in the power ratio between patients with the peritoneal cavity empty of dialysis fluid and controls (8.6 +/- 4.8 vs 7.5 +/- 2.2). The subgroup of patients with no dyspepsia had a significantly higher power ratio compared to those with dyspepsia both on dialysis and with the peritoneal cavity empty of dialysis fluid (39.4 +/- 13.7 vs 12.4 +/- 5.2 and 29.2 +/- 21.5 vs 2.8 +/- 0.4 respectively, P < 0.05). In conclusion, there was no significant difference in gastric myoelectrical activity between patients with the peritoneal cavity empty of dialysis fluid and controls. Dialysis fluid in the peritoneal cavity seems to enforce the gastric myoelectrical signal. PMID- 11768254 TI - Effect of meal size and test duration on gastric emptying and gastric myoelectrical activity as determined with simultaneous [13C]octanoate breath test and electrogastrography in normal subjects using a muffin meal. AB - Our purpose was to determine the effect of meal size on gastric emptying (GE) as measured by octanoate breath test (OBT), to determine the effect of the duration of breath collections on assessment of GE by OBT, and to determine the effect of meal size on gastric myoelectrical activity as measured by electrogastrography (EGG). Fourteen normal subjects underwent two modified [13C]OBTs using muffin meals of 250 or 350 kcal mixed with 100 mg [13C]sodium octanoate. T(1/2) for GE was determined for both the entire postprandial 6-hr breath collection and a truncated initial 4-hr data set. EGG was recorded for 30 min prior to the muffin meal and 4 hr postprandially. Using the 6-hr breath collection data, the T(1/2) was 177 +/- 7 (mean +/- SEM) for the 350-kcal meal compared to 153 +/- 7 min (P < 0.01) for the 250-kcal meal. Using the 4-hr data, the T(1/2) for the 350-kcal meal was 244 +/- 32 min compared to 165 +/- 12 min (P < 0.05) for the 250-kcal meal. The ratio of postprandial to fasting EGG power of the dominant frequency for the 350-kcal meal (1.9 +/- 0.4) was higher than that for the 250-kcal meal (1.3 +/- 0.6). T(1/2) for the 350-kcal meal using 4- and 6-hr data was significantly correlated with the 4-hr power ratio (r = 0.68 and 0.67; P < 0.05, respectively), but poorly correlated for the 250-kcal meal. In conclusions, GE and EGG are affected by meal size. Using the muffin-based [13C]OBT, T(1/2) for the 350-kcal meal was significantly longer than for a 250-kcal meal. Longer T(1/2) values were obtained with shorter breath sampling durations. The postprandial to fasting power ratio for the 350-kcal meal was greater than that for the 250-kcal meal. PMID- 11768256 TI - Gastric adenocarcinoma metastatic to the prostate gland: a rare case and review of the literature. PMID- 11768257 TI - Endoscopy for hematochezia in patients under 50 years of age. AB - The optimal strategy for evaluating rectal bleeding in young persons is unknown. This study examines the prevalence of adenomatous neoplasms identified at endoscopy for rectal bleeding. Retrospective cross-sectional analysis was made of patients under 50 years of age undergoing elective outpatient colonoscopy or flexible sigmoidoscopy for hematochezia. In all, 570 patients (309 F/261 M) met our inclusion criteria. The prevalence of neoplasms was 3.8% (95% CI 1.2-8.5%) among persons under 30, 2.8% (95% CI 0.9-6.3%) among persons age 30-39, and 10.9% (95% CI 7.4-15.4%) among persons age 40-49. The prevalence of neoplasms was higher in persons over age 40 (relative risk 3.43, 95% CI 1.70-6.94). Six of seven advanced neoplasms were identified in persons over age 40 (relative risk 7.4, 95% CI 0.89-60.7). In conclusion, the prevalence of colonic neoplasms in patients 40-50 years old with hematochezia is substantial. Among those persons younger than 40 years, the prevalence of colonic neoplasms is significantly lower. PMID- 11768258 TI - Inhibition of telomerase by site-specific ribonucleases in gastric and esophageal adenocarcinoma. AB - Increased expression of telomerase is critical in the pathogenesis of cancer. Telomerase expression is reported variably in foregut cancers, possibly as a result of telomerase inhibition or ribonucleases. We performed experiments to assess telomerase and telomerase RNA expression in foregut cancers and to quantify and characterize telomerase inhibition. Cancer specimens were obtained from 27 patients. Telomerase activity of cancers was determined by the telomeric repeat amplification protocol, the presence of telomerase RNA component (hTERC) by reverse transcription PCR, and the quantity of telomerase inhibitors in mixing experiments. Ribonuclease activity was measured by assessing degradation of labeled RNA by cancers. Telomerase was found in 8/11 adenocarcinomas of the esophagus or gastroesophageal junction and 6/16 distal gastric adenocarcinomas; hTERC was detectable in all cancers. Telomerase inhibition was more marked in distal compared to proximal adenocarcinomas (P = 0.01) and correlated with ribonuclease activity (rS = 0.65). Ribonucleases contribute significantly to telomerase inhibitory activity detectable in foregut cancer specimens. In vitro, the presence of telomerase inhibitors in some specimens did not prevent the detection of telomerase by the TRAP assay. This suggests a more complex relationship between telomerase and its inhibitors. Site-specificity of telomerase inhibitors generally and ribonuclease activity specifically suggests a putative regulatory role in vivo. PMID- 11768259 TI - Symptom control may improve food intake, body composition, and aspects of quality of life after gastrectomy in cancer patients. AB - That severe malnutrition affects body function and psychological well-being is well documented. We addressed the question of whether quality of life relates to changes in variables such as food intake, body composition, and gastrointestinal symptomatology after gastrectomy for gastric cancer. Thirty-two patients undergoing gastric resection had their dietary intake, body composition, and specific and general aspects of quality of life determined preoperatively, at 12 months and, in the 15 surviving patients, several years after the operation. The patients lost 10% of their preoperative weight (mainly body fat) during the first year. Food intake did not correlate to changes in body composition or quality of life. Gastrointestinal symptoms adversely related to changes in lean body mass, meal size, and general aspects of quality of life for a long time after the operation. Gastrointestinal symptom control seems important to minimize impairment in quality of life, body composition, and eating after gastrectomy. PMID- 11768260 TI - Cytological screening for Barrett's esophagus using a prototype flexible mesh catheter. AB - The current cost of endoscopically screening patients with gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) is considerable. A nonendoscopic device that allows for screening of these patients would offer significant cost savings. This pilot study evaluates the utility of cytologically diagnosing BE using a prototype flexible mesh catheter. Patients with known BE undergoing indicated surveillance endoscopy were enrolled in the study. Cytology specimens were obtained using a prototype flexible catheter and were evaluated for the presence of glandular cells, goblet cells, squamous cells, inflammation, and dysplasia. Eleven patients with BE were enrolled in the study. None of the patients experienced complications. Specimens from eight patients (73%) were adequate for evaluation and seven of these patients (87.5%) had goblet cells diagnostic for BE. In conclusion, flexible mesh catheters potentially offer a sensitive, inexpensive, and minimally invasive approach to evaluating patients with GERD and BE. PMID- 11768261 TI - Role of diaphragmatic crura and lower esophageal sphincter in gastroesophageal reflux disease: manometric and pH-metric study of small hiatal hernia. AB - The rapid pull-through (RPT) technique during esophageal manometry helps to identify various pressure profiles of hiatal hernia (HH), based on the presence of two high pressure zones: the diaphragmatic crura (DC) and the lower esophageal sphincter (LES). Our aim was to correlate different HH profiles with frequency of reflux episodes in patients with gastroesophageal reflux disease (GERD). Seventy eight patients with GERD and HH underwent esophageal manometry with RPT and were grouped according to the prevalent pressure profile of HH. Twenty-four-hour pH metry served to quantify traditional (TR) and nontraditional refluxes (drop of 1 pH unit with pH > 4 or pH < 4 and time < 5 sec) (NTR) during total, upright, and recumbent periods. The group with a prevalent "flat" HH profile, representing LES and DC impairment, had significantly more TRs in total time of reflux (P < 0.01) and in recumbent and upright periods (P < 0.05) compared to the group with a prevalence of the two pressure peaks, corresponding to LES and DC efficiency. However, the group with the flat profile had significantly more NTRs + TRs than the group with pressure peaks in total time (P < 0.01) and recumbent position (P < 0.001) but not in the upright position. Hiatal hernia predisposes to GERD, but only the associated impairment of the LES and diaphragmatic crura pressures represents a condition of high risk for gastroesophageal reflux events. PMID- 11768262 TI - Appropriateness of upper gastrointestinal endoscopy: a hospital-based study. AB - Aims of this study were to evaluate: (1) whether upper gastrointestinal endoscopy (UGE) is used appropriately according to the American Society for Gastrointestinal Endoscopy (ASGE) and British Society of Gastroenterology (BSG) guidelines in a hospital setting and (2) whether there is any relationship between appropriateness of UGE and the presence of lesions detected by endoscopy. Indications and endoscopic findings for 734 consecutive UGE performed in 697 inpatients were retrospectively evaluated using ASGE and BSG guidelines to determine appropriateness of referrals. UGE showing endoscopic findings that had direct therapeutic or prognostic consequences were classified as "positive"; the other UGEs were classified as "negative." In all, 46% of UGEs were "positive," 54% "negative," and 61.7% and 23.2% of UGEs were inappropriate according to ASGE and BSG guidelines, respectively (P < 0.001). The probability of finding a positive endoscopy was significantly higher in UGE rated as appropriate than in those rated as inappropriate on the basis of ASGE guidelines (P < 0.001), but not on the basis of BSG guidelines. Endoscopies rated as inappropriate according to ASGE and BSG criteria showed a positive finding in 37.3% and 42.3% of cases, respectively (not significant difference). Multivariate analysis showed that the positive finding is directly related to age (P < 0.05), male gender (P < 0.001), prior UGE (P < 0.05), hematemesis (P < 0.001), and inversely related with upper abdominal pain (P < 0.01) and dyspepsia (P < 0.05). In hospitalized patients, UGE is frequently used for inappropriate indications, according to both ASGE and BSG guidelines. However, the actual clinical usefulness of appropriateness criteria, such as those proposed by ASGE and BSG, is questionable, as their strict observance could lead to missing a large number of significant endoscopic findings. PMID- 11768263 TI - Pretreatment gastric histology is helpful to predict the symptomatic response after H. pylori eradication in patients with nonulcer dyspepsia. AB - This study aimed to test whether pretreatment gastric pathology in H. pylori infected nonulcer dyspepsia (HpNUD) patients is relevant to and predictive of the symptomatic response after H. pylori eradication. Anti-H. pylori triple therapy was administered to 250 HpNUD patients, enrolled as the therapy group. In addition, 60 patients were enrolled as the control group, in which omeprazole was an alternatives to the triple therapy. Pretreatment gastric histology was evaluated thoroughly by the updated Sydney system. A [13C] urea breath test was also performed to evaluate the H. pylori eradication two months and 12 months later. For each patient, the baseline, month 2, and month 12 symptom scores were assessed for the month 2 or month 12 residual symptom ratio (RSR-2m or RSR-12m), calculated from: 100% x month 2 or month 12 score/baseline score. Based on either RSR-2m or RSR-12m, patients were categorized as good response (RSR < 50%), moderate response (50-70%), and poor response (> 70%) subgroups in both therapy and control groups to define the short-term and long-term symptomatic responses. Patients with successful H. pylori eradication in the therapy group showed a higher incidence of good symptomatic response (RSR < 50%) than those from the control group (month 2: 30.3 vs 12%, P < 0.05; month 12: 34.7 vs 17.1%, P < 0.05). Univariate and multivariate analysis disclosed that patients with a higher acute inflammation score (AIS) and the lowest incidence of lymphoid follicles (LF) at pretreatment gastric histology are predisposed to having a good symptom response after H. pylori eradication (P < 0.05). For HpNUD patients who have an AIS of more than three and an absence of LF at gastric histology, more than 85% had good short-term (month 2) and long-term (month 12) symptomatic relief after H. pylori eradication. In conclusion, nearly 30% of HpNUD patients can obtain symptomatic relief following H. pylori eradication. The pretreatment gastric histology of HpNUD can be helpful to monitor the symptomatic response after H. pylori eradication. PMID- 11768264 TI - Mechanisms and roles of neutrophil infiltration in stress-induced gastric injury in rats. AB - Water-immersion and restraint stress is associated with an increase in neutrophil infiltration into the gastric mucosa, but the mechanism responsible for this infiltration is unclear. We investigated the involvement of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) in neutrophil infiltration in stress-induced gastric injury in rats. Rats were administered neutralizing antibody against ICAM-1 or TNF-alpha and were subjected to induction of gastric injury by 6-hr water-immersion and restraint stress. To evaluate the relationship between gastric acid and neutrophil infiltration, some rats were given cimetidine before administration of stress. Neutralizing antibodies inhibited both the lesion formation and the increase in myeloperoxidase activity induced by stress. Expression of ICAM-1 on endothelial cells was increased by stress, accompanied by an increase of TNF-alpha-positive cells. Antibody against TNF-alpha inhibited this increase in ICAM-1 expression. Cimetidine almost completely inhibited gastric lesions, but did not affect myeloperoxidase activity. In conclusion, neutrophil infiltration in stress induced gastric injury may be mediated by ICAM-1 and TNF-alpha, but not gastric acid, and may play crucial roles in the progression of gastric injury. PMID- 11768265 TI - Reduction of peptic ulcer disease and Helicobacter pylori infection but increase of reflux esophagitis in Western Sydney between 1990 and 1998. AB - We aimed to determine if changes in the patterns of upper gastrointestinal diseases at endoscopy have occurred over the past decade. Retrospectively, 917 consecutive patients were selected based on upper endoscopy between June 1 and August 31, in 1990 (n = 217), 1994 (n = 270), and 1998 (n = 430). Demographic, clinical, endoscopic, and histological information were extracted from the medical records on a standardized case record form. Over the eight-year period, follow-up of peptic ulcer (15%, 5%, and 5%, respectively, in 1990, 1994, and 1998, df = 2, P < 0.001), bleeding (22%, 14%, and 13%, P = 0.008), and nausea/vomiting (15%, 16%, and 10%, df = 2, P = 0.003) had become less frequent, but reflux (21%, 19%, and 34%, df = 2, P < 0.001) and dyspepsia (24%, 43%, and 32%, df = 2, P < 0.001) more frequent indications for upper endoscopy. The prevalence of peptic ulcer disease decreased (22%, 15%, and 13%, df = 2, P = 0.025), but the prevalence of reflux esophagitis increased significantly (29%, 30%, and 39%, df = 2, P = 0.010). The prevalence of both the use of nonsteroidal antiinflammatory drugs (NSAIDs) (18%, 20%, and 11%, respectively, in 1990, 1994, and 1998, df = 2, P = 0.004) and H. pylori infection (39% in 1994 and 30% in 1998, df = 1, P = 0.032) decreased. Overall, NSAID use was independently associated with gastric ulcers (OR = 2.39, 95% CI 1.21-4.73, chi2 = 6.31, df = 1, P = 0.012), but not esophagitis. H. pylori infection was independently associated with duodenal ulcers (OR = 4.74, 95% CI 2.30-9.77, chi2 = 17.8, df = 1, P < 0.001), histologically chronic (OR = 166.8, 95% CI 76.1-365.4, chi2 = 313.0, df = 1, P < 0.001) and active (OR = 30.1, 95% CI 17.0-53.5, chi2 = 189.7, df = 1, P < 0.001) gastritis and lymphoid aggregates (OR = 5.49, 95% CI 3.02-9.97, chi2 = 36.3, df = 1, P < 0.001). In conclusion, the prevalence of peptic ulcer disease appears to have been decreasing, whereas reflux esophagitis has been increasing over the past decade in Western Sydney. The decreased use of NSAIDs and decline of H. pylori infection have likely both contributed to the reduction of peptic ulcer disease, but the increase in reflux esophagitis remains to be fully explained. PMID- 11768267 TI - Superoxide anion and nitric oxide in high-grade esophagitis induced by acid and pepsin in rabbits. AB - It has been proposed that free radicals are involved in the pathogenesis of esophageal mucosal damage induced by acid and pepsin. Recent data have suggested that nitric oxide (NO) is involved in the mucosal defense of the esophagus and that superoxide anion plays a minor role in low-grade esophagitis. To study the role and potential interaction of NO and superoxide anion in an experimental model of high-grade esophagitis, acidified pepsin was perfused (45 min/12 hr) for five days in rabbits with different agents to modulate the generation of these radicals. Measurements included both macroscopic and microscopic mucosal damage, superoxide anion generation, NO synthase mucosal activity, and peroxynitrite formation. High-grade esophagitis was associated with mucosal superoxide anion generation. Treatment with exogenous superoxide dismutase completely prevented mucosal damage. The perfusion of acidified pepsin in the lumen of the esophagus was initially associated with increased NO synthase mucosal activity but decreased with the progression of damage. Generation of peroxynitrites was present in those cases with severe damage. Treatment with NO-modifying agents did not induce consistent modification of mucosal damage. It is concluded that superoxide anion is involved in the induction of high-grade esophagitis and that it interacts with nitric oxide to generate peroxynitrite radicals in this model. Superoxide dismutase but not NO-donor-modifying agents might have a therapeutic role in preventing severe esophageal mucosal damage induced by acid and pepsin. PMID- 11768266 TI - No protective role of Helicobacter pylori in the pathogenesis of reflux esophagitis in patients with duodenal or benign gastric ulcer in Korea. AB - Little is known about the relationship between H. pylori infection and reflux esophagitis. To evaluate whether or not H. pylori plays a protective role in the pathogenesis of reflux esophagitis, the prevalence rates of reflux esophagitis depending on H. pylori status in consecutively diagnosed duodenal ulcer or benign gastric ulcer patients were evaluated. In addition, the incidence rates of reflux esophagitis depending on H. pylori status were evaluated for those patients who received follow-up endoscopy at least 6 months after eradication treatment. The prevalence rates of reflux esophagitis were 8.0% (2 patients) in the 25 H. pylori negative duodenal ulcer group patients and 6.5% (36 patients) in the 555 H. pylori-positive duodenal ulcer group patients, and there was no statistical difference. Similarly, that of gastric ulcer patients was 9.4% (32 patients) in the 340 H. pylori-positive group patients, slightly higher than that in the 41 H. pylori-negative group patients 4.9% (2 patients), but without statistical significance. After eradication treatment the reflux esophagitis incidence rates were 2.5% (2 patients) in the 81 H. pylori-eradicated duodenal ulcer group patients and 7.7% (3 patients) in the 39 noneradicated duodenal ulcer group patients, and there was no statistical difference. Similarly, those of gastric ulcer patients were 6.8% (3 patients) in the 44 H. pylori-eradicated and 8.7% (2 patients) in the 23 noneradicated group patients again without statistical difference. These results suggest that H. pylori does not play a protective role in the pathogenesis of reflux esophagitis in patients with duodenal or gastric ulcer in Korea. PMID- 11768268 TI - Helicobacter pylori infection is not associated with subclinical hepatic encephalopathy in stable cirrhotic patients. AB - The importance of ammonia-producing Helicobacter pylori infection as a cause of subclinical encephalopathy in cirrhosis was investigated. In addition, a single psychometric test that can reliably detect subclinical hepatic encephalopathy was sought. Out-patients with cirrhosis and no overt encephalopathy underwent [14C]urea breath testing once and psychometric testing on two separate occasions, with an intervening course of clarithromycin/omeprazole if they had subclinical encephalopathy (two of four psychometric tests abnormal). Subclinical encephalopathy was present in 27 of 69 patients (39%), and Helicobacter pylori infection in 14 of 69 (20%). There was no association between the two conditions (P = 0.769). Subclinical encephalopathy resolved in 75% of treated Helicobacter pylori-positive patients and 37.5% of treated Helicobacter pylori-negative patients (P = 0.285). Number connection test-B had high reproducibility among untreated patients (R = 0.655) and high correlation (P < or = 0.01) with three surrogate gold standards. In stable cirrhotic patients, subclinical hepatic encephalopathy was found to: (1) have a high prevalence, (2) not be associated with Helicobacter pylori infection, and (3) be readily detected with the number connection test-B alone. PMID- 11768269 TI - Presence of bacterial infection in bleeding cirrhotic patients is independently associated with early mortality and failure to control bleeding. AB - Bacterial infection is strongly associated with gastrointestinal bleeding in cirrhotic patients and seems to be related with the failure to control bleeding. The aims of this study were to assess the influence of infections on the failure to control bleeding and death in cirrhotic patients without antibiotic prophylaxis. Ninety-one consecutive bleeding cirrhotic patients were analyzed. Bleeding was managed using somatostatin with sclerotherapy for active bleeding. Screening for bacterial infection (analysis and culture of blood, urine, ascitic and other fluids, together with chest radiography) was made at time 0 and when clinical signs suggested infection. The cause of bleeding was variceal in 72 (79%) patients. Failure to control bleeding occurred in 24 (26%) patients, and 10 (11%) of the patients died. Compared with the group without infection, failure to control bleeding (65% vs 15%; P < 0.001) and mortality (40% vs 3%; P < 0.001), were observed more frequently in patients with infection. Multivariate analysis showed that bacterial infection (OR = 9.7; P < 0.001) and the presence of shock (OR = 3.5; P < 0.05) were independently associated with failure to control bleeding. Bacterial infection (OR = 12.6; P < 0.01), encephalopathy (OR = 6.9; P < 0.05), and shock (OR = 5.8; P < 0.05) were identified as predictive of death. In conclusion, in bleeding cirrhotic patients bacterial infection is associated with failure to control bleeding as well as mortality. PMID- 11768270 TI - Acute valproate-associated microvesicular steatosis: could the [13C]methionine breath test be useful to assess liver mitochondrial function? AB - Microvesicular steatosis is a potentially severe manifestation of valproic acid hepatotoxicity due to an acquired impairment of mitochondrial function. Tests currently used to investigate mitochondrial fonction are cumbersome and cannot be used routinely. We report on a noninvasive breath test using [13C]methionine for estimation of mitochondrial function in a case of pure severe valproic acid overdose-induced microvesicular changes. The initially abnormal breath test improved together with the recovery of liver failure. In conclusion, this observation suggests that the [13C]methionine breath test may provide a noninvasive estimate of hepatic mitochondrial function in vivo. PMID- 11768271 TI - Expression of bilirubin UDP-glucuronosyltransferase (bUGT) throughout fetal development: intrasplenic transplantation into Gunn rats to correct enzymatic deficiency. AB - The aim of this work was to determine the pattern of expression of hepatic bilirubin UDP-glucuronosyltransferase throughout fetal development in rats, with the purpose of using fetal hepatocytes at the most appropiate stage of development for transplantation into Gunn rats lacking bilirubin UDP glucuronosyltransferase activity and then assessing the therapeutic capacity of the implants. The results show that at day 13 of gestational life there is already bilirubin UDP-glucuronosyltransferase gene expression. Twenty-one-day fetal hepatocyte transplantation was also performed into the spleens of hyperbilirubinemic Gunn rats, when alpha-fetoprotein mRNA is still detectable. At 15, 30, and 90 days after transplantation, a mild decrease in total bilirubin serum levels was observed. An increase in bile conjugated bilirubin also was observed at 30 and 90 days. These data suggest the favorable evolution of transplanted cells and show its feasibility for therapy. PMID- 11768273 TI - Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder. AB - Cholecystokinin is the most important stimulant of postprandial gallbladder contraction, and a regulator of gallbladder fasting tone. The aim of this study was to evaluate the effect of dexloxiglumide on isolated human gallbladder contraction induced by cholecystokinin-octapeptide and to compare this effect to that of lorglumide and amiglumide, two glutaramic acid analogs of dexloxiglumide. The negative logarithms of the antagonist dissociation constant (pK(B)) values were 7.00 +/- 0.14, 6.95 +/- 0.11, and 6.71 +/- 0.10 for lorglumide, dexloxiglumide, and amiglumide, respectively. Dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. A similar effect was obtained both with lorglumide and amiglumide. Moreover, the slopes for the three antagonists did not differ significantly from unity. These data show that the three molecules have a potent antagonistic effect, of a competitive nature, on gallbladder cholecystokinin type 1 receptors. It may be concluded that dexloxiglumide, lorglumide, and amiglumide exhibit a promising therapeutic profile for biliary colic and other gastrointestinal disorders in which CCK1 receptors play important physiological roles. PMID- 11768272 TI - Antioxidants inhibit cytokine production and suppress NF-kappaB activation in CAPAN-1 and CAPAN-2 cell lines. AB - Interleukin (IL) -6 and IL-8 are cytokines that have been shown to play a role in several pancreatic diseases, including acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma. Previously, we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) and gram-negative bacterial lipopolysaccharide stimulate production of IL-6 and IL-8 and activation of the transcription factor NF-kappaB in the well-differentiated pancreatic ductal adenocarcinoma cell lines CAPAN-1 and CAPAN-2. In these studies we have examined the effect of chain breaking and glutathione-enhancing antioxidants on NF-kappaB activation and production of IL-6 and IL-8 in these cell lines. Generally, suppression of NF kappaB activation correlated well with inhibition of IL-6 and IL-8 secretion. In the CAPAN-2 cell line, antioxidants inhibited both NF-kappaB activation and IL-6 and IL-8 secretion. In the CAPAN-1 cell line, antioxidants generally failed to suppress both NF-kappaB activation and IL-6 and IL-8 secretion. The single exception was the chain-breaking antioxidant butylated hydroxyanisole (BHA), which markedly inhibited IL-6 and IL-8 secretion, but had no effect on NF-kappaB activation. These findings may have implications for the treatment of acute and chronic pancreatitis and pancreatic cancer. PMID- 11768274 TI - Endoscopic findings of a pancreatic glucagonoma. PMID- 11768275 TI - Pigment gallstone formation following proctocolectomy. PMID- 11768276 TI - Establishing evidence for Chinese medicine: a case example of irritable bowel syndrome. AB - Traditional Chinese medicine (TCM) is now used by a broad cross-section of the western community. It offers some attraction because it provides new options for treatment, an individualized approach, and potentially avoidance of harsh drugs or surgery. However, despite this growing popularity there is debate as to its evidence base. Few TCM trials have been performed in the West, and previous Chinese TCM trials have been perceived to lack methodological rigour. Establishing and applying stronger clinical trial methodologies in TCM is imperative for its integration with modern medicine and achieving the end goal of creating options for patient care. A clinical trial was designed using a variety of approaches to promote methodological rigour whilst allowing the flexibility required in TCM practice. Irritable bowel syndrome (IBS) was selected as the disease focus, creating the possibility of tailoring TCM treatments to the variable clinical presentations of IBS. Patients were randomised to receive individually tailored treatment (n = 38), a standard Chinese herbal formulation (n = 43), or placebo (n = 35) for 16 weeks. Patients, gastroenterologists and herbalists were all blinded as to treatment group. Both standard and individualized treatments were significantly more effective than the placebo treatment on all key outcome measures. However, this study failed to confirm the added value of tailoring treatments. Chinese herbal formulations individually tailored to the patient proved no more effective than the standard treatment on all measures. Nevertheless, the trial demonstrates it is possible to test individualization of treatment whilst adhering to conventional trial protocols. Clinical trials can be designed that accommodate nuances of TCM practice. This study also shows Chinese herbal medicine may offer assistance to some patients with IBS and may prove as effective as current pharmaceutical approaches. Further validation of TCM interventions is required. PMID- 11768277 TI - Modulation of Na, K-ATPase activity by immunoglobulins--1. Effects of IgM on the Na, K-ATPase activity in glomerulonephritis. AB - BACKGROUND: In the cases of acute glomerulonephritis unfavourable outcome is related to increased blood concentration of IgM. We assumed that pathologic changes in glomerulonephritis might result from direct binding of IgM antibodies to Na, K-ATPase in the nephron channels. METHODS: The study involved 30 patients suffering from glomerulonephritis. Na, K-ATPase activity was studied in the erythrocytes of these patients and healthy controls at different concentrations of Mg2+ ions in the incubation media. RESULTS: Na, K-ATPase activity in the erythrocytes of healthy subjects was shown to gradually diminish at the increasing concentrations of Mg2+ ions. Another pattern was displayed for the enzyme activity in glomerulonephritis patients--a sharp decrease of the enzymatic activity at 6 mM Mg2+, as compared with that at 3 mM, and restoration to essentially the starting level at 12 mM. Incubation of erythrocytes from healthy subjects with plasma from glomerulonephritis patients changed the response of Na, K-ATPase activity to Mg2+ concentration to that typical for glomerulonephritis patients. Analogous changes were caused by adding IgM antibodies to whole blood. It was demonstrated in vivo, that hypotonic artificial mineralised water "Marina" restores Na, K-ATPase activity in erythrocytes of glomerulonephritis patients and reduces proteinuria. CONCLUSIONS: We have postulated, that the changes in the Na, K-ATPase activity, typical for glomerulonephritis patients are caused by the interaction of the enzyme with immunoglobulin M antibodies. The lack of difference between the Na, K-ATPase activity in erythrocyte ghosts from healthy subjects and glomerulonephritis patients suggests that the immunoglobulin M attachment site is on the outer membrane and that the toxic factor could be removed. PMID- 11768278 TI - Prediction of in-hospital mortality in patients with myocardial infarction using APACHE II system. AB - BACKGROUND: The acute physiology and chronic health evaluation (APACHE) scoring system has been validated in many different patient populations, however, patients with myocardial infarction (MI) were not included in the original data base. To evaluate the ability of APACHE scoring system in predicting in-hospital mortality, 694 patients with MI were studied. METHODS: Data had been collected prospectively in an ICU computer database in the past 3 years. Patients admitted in coronary care unit with acute MI or acute coronary syndrome who had previous history of MI were all included. Patients were divided into survivor and non survivor data sets. Multiple logistic regression analysis was evaluated on the variables of APACHE II score to determine which variables could predict in hospital mortality. A logistic regression model was used to study the mortality curves. The differences of APACHE II scores between survivors and non-survivors were compared. Correlation between observed and predicted mortality was also assessed. RESULTS: According to the statistical analysis, the non-survivors tended to have significantly greater APACHE II scores than those of survivors. The APACHE II values of non-survivors and survivors were 23.64 +/- 9.41 versus 13.35 +/- 7.14 (p < 0.001), respectively. Using multiple logistic regression analysis, we found that age, creatinine, coma scale, sodium and APACHE II score were capable of predicting the in-hospital mortality (p < 0.05). With use of the logistic model, a good correlation of predicted mortality rate to observed mortality rate was found (r = 0.992). This study demonstrated that lower APACHE II scores predicted survival while high scores predicted mortality. Mortality rate increased significantly when APACHE II score was > 25. An APACHE II score greater than 28.25 predicted a more than 50% in-hospital mortality. CONCLUSIONS: This study demonstrates that the APACHE II scoring system is capable of predicting mortality in patients with MI, which makes this modality more applicable in the busy intensive care unit. PMID- 11768279 TI - Can APACHE II score touch the heart to predict AMI mortality? PMID- 11768280 TI - Electromyographic evaluation in children with spina bifida. AB - BACKGROUND: It is controversial to predict ambulation potential using neurological level or specific pattern of muscle strength in patients with spina bifida. We attempted to analyze the relationship between the mobility outcome and its influencing factors utilizing electromyography to study motor unit activity in lower limbs. A subsidiary aim was to evaluate the external anal sphincter with electromyography and to determine the relevant factors of bowel and bladder functions. METHODS: Among 156 patients with spina bifida who had received electromyographic examination and were followed at the out-patient clinic between 1998 and 2000, functional assessment with Pediatric Evaluation of Disability Inventory (PEDI) was applied in 47 randomly selected patients. Other assessments included clinical neurological examination, bowel and bladder function survey, and ambulation evaluation. We correlated the parameters of electromyography with the ambulatory ability and PEDI scores. The innervation of external sphincter was compared between groups with or without neurogenic bowel or bladder dysfunction. RESULTS: The innervations of hip adductor and quadriceps were found to correlate with walking ability (p < 0.01); above muscles as well as anterior tibialis, and gastrocnemius were related to PEDI scores (p < 0.01). The neurological level still manifested correlation with walking ability (p < 0.05) and PEDI scores (p < 0.01). Both denervation potentials and recruitment pattern were important parameters for ambulation and mobility prediction. Significant difference was obtained in denervation patentials of sphincter within bowel groups (p = 0.036) and bladder groups (p = 0.016). CONCLUSIONS: Both traditional neurological level and specific muscle innervation exert crucial influence on walking and mobility functions. Electromyographic assessment demonstrates its contribution in prediction of functional outcome in spina bifida. PMID- 11768281 TI - Electromyographic assessment of neurological function in patients with myelomeningocele caused by spina bifida. PMID- 11768282 TI - Preservation of anal sphincter function after hemorrhoidectomy under local anesthesia. AB - BACKGROUND: This is a prospective study designed to confirm a simple, effective method of hemorrhoidectomy that can be accomplished by simple local anesthesia with good preservation of anal sphincter function both clinically and manometrically. METHODS: Eighty consecutive patients with prolapsed mixed hemorrhoids were operated with standard closed hemorrhoidectomy under local anesthesia. Pre- and post-operative assessments of anal continent function and anorectal manometry were performed. Maximal basal pressure (MBP), maximal contraction pressure (MCP), squeeze pressure (SP), rectoanal inhibitory reflex (RAIR), functional length (FL), volumes at the first sensation of rectal fullness (V sense), urge of defecation (V urge), and intolerance (V max.) were measured. The pre-and post-operative data were compared with two tailed paired Student t test. Statistical significance was considered asp-value less than 0.05. RESULTS: All 80 patients were completely followed up and studied. No patient had any degree of anal incontinence before and 6 months after hemorrhoidectomy. There was significant change in V sense and V urge after operation. However, MBP, MCP, SP, FL, RAIR, and V max. remained unchanged. CONCLUSIONS: Standard closed hemorrhoidectomy supplemented with appropriate submucosal dissection under adequate local anesthesia is simple and effective for the treatment of prolapsed hemorrhoids. The function of anal sphincter, both clinically and manometrically, can be well preserved. PMID- 11768283 TI - Characteristics of patients at a Taipei summer rock concert festival. AB - BACKGROUND: Rock concerts are popular mass gatherings in Taiwan. Millions of fans participate in rock concerts in Taiwan each year. However, there were no reports on the characteristics of the patients seen in rock concerts in Taiwan. METHODS: Medical care for a summer rock concert festival held in an outdoor stadium in Taipei was coordinated by emergency physicians of a medical center. About 50,000 attendees participated in the two-night concert. Three stations were set up to provide advanced medical care. A standardized form was used to collect information about patients. RESULTS: A total of 28 cases visited the medical stations, fourteen cases each day. They were aged from 13 to 40 years, with an average of 20.8 +/- 6.4. Twenty-one cases were female and seven were male. Twenty two (79%) were spectators, five (18%) were on-duty staff, and one was a by stander. Based on an estimation of totally 50,000 participants in the stadium for this two-night festival, the medical use rate was roughly 5.6 PPTT (patients per ten thousand attendees). The most common major problem was fainting which accounted for 13 cases (46%). Of these 13 cases, three cases (23%) lost consciousness and 12 cases (92%) were female. Sixteen cases (57%) were classified as requiring ALS (advanced life support) and 12 cases (43%) as requiring BLS (basic life support). Most cases improved and were discharged after onsite treatment. Only one case was transferred by ambulance due to persistent chest pain. However, she recovered several hours later. CONCLUSIONS: By this preliminary data, first reported in Taiwan, we found that the most common problem was fainting. More than half of the cases seen at the concert required advanced life support. A well-designed emergency medical service (EMS) system is mandatory to provide services for these events. PMID- 11768284 TI - Ascending aorta to lower limbs revascularization for reoperation via ministernotomy. AB - The extra-anatomic bypasses, femorofemoral or axillofemoral, have been performed in selected patients for lower extremity revascularization of aortoiliac occlusion. However, significant graft occlusion rate does exist and reoperation constitutes an increasing proportion of vascular surgery practice. We presented our experience in a high-risk patient who received bypass surgery for the third time using the ascending aorta as the source of inflow with good result. PMID- 11768285 TI - Acute myocardial infarction caused by aortic dissection. AB - Clinical presentation of aortic dissection is similar to that of acute myocardial infarction (AMI). Clinical differential diagnoses from lethal chest pain in emergency department include AMI, aortic dissection, pulmonary embolism, tension pneumothorax, etc. Thrombolytic therapy for recanalization of thrombotic occluded coronary artery in AMI must be considered, but it is absolutely contraindicated for aortic dissection. However, AMI secondary to aortic dissection is a rare condition, which might be caused by compression of the coronary arteries by a hematoma or extension of the dissection into the coronary arterial wall. Surgery is the first choice for AMI secondary to aortic dissection caused by extension of dissection into the coronary arterial wall. We present a case of inferior wall AMI caused by type I aortic dissection with presentation of chest pain and hemiparaplegia of right lower limb. PMID- 11768286 TI - Foix-Chavany-Marie syndrome. AB - Anarthria and bilateral central faciolinguopharyngeomasticatory paralysis with automatic voluntary dissociation are the clinical hallmarks of Foix-Chavany-Marie syndrome (FCMS), the cortico-subcortial type of suprabulbar palsy. We present a 64-year-old man who was admitted due to acute onset of speechlessness for days. Neurological examinations demonstrated typical features of FCMS. Cranial MRI showed a right opercular lesion and several lacunar infarcts in bilateral hemispheres. Hexamethylpropylenamine oxime (HMPAO) brain SPECT revealed hypoperfusion in bilateral opercular regions and notably on the right side. In review of previous reports, the most common etiology of FCMS is stroke in the region of either operculum. Our case may be a good example of FCMS after multiple cerebrovascular insults over bilateral opercular cortico-subcortical areas as demonstrated in MRI and SPECT studies. PMID- 11768287 TI - Spontaneous uterine perforation mimicking ectopic pregnancy as the initial presentation of placental site trophoblastic tumor. AB - Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD), with only 100 cases reported in the literature. Irregular vaginal bleeding has been reported to be the most common presenting symptom, however, spontaneous uterine perforation, mimicking ectopic pregnancy, as the initial presentation is extremely rare, and has not yet been reported in the Chinese literature. Herein, we report a 26-year-old female with PSTT complicating with uterine perforation that mimicked ectopic pregnancy as the initial presentation. She received wide excision of the uterine perforation margin only and now remains disease-free, 2 years after the operation. Reviewing the literature, while most cases of PSTT behave a benign fashion, some exhibit malignant behavior; surgery remains the mainstay of therapy. For patients whose disease is limited to the uterus, simple total abdominal hysterectomy is the treatment of choice. For patients with extensive or metastatic disease, cytoreductive surgery (total abdominal hysterectomy and resection of extrauterine tumor load) combined with chemotherapy should be applied. Etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) chemotherapy appears superior to other available chemotherapeutic regimens in the treatment PMID- 11768288 TI - Klebsiella pneumoniae orbital cellulitis. AB - We present a case of orbital cellulitis due to Klebsiellapneumoniae infection. The computed tomography revealed cellulitis over the right cheek with abscess formation in the right eyelid and ipsilateral chronic obstructive sinusitis. Incision and drainage of orbital abscess and functional endoscopic sinus surgery were performed sequentially. Klebsiella pneumoniae was confirmed via culture from these two lesions. The patient achieved complete remission without sequalae after surgical intervention and systemic antibiotics. We describe a successfully treated case of Klebsiella pneumoniae orbital cellulitis, which has never been reported before. PMID- 11768289 TI - Quantitative evaluation of capacity-limited hepatobiliary transport based on hepatocellular diffusion model by MULTI(FEM). AB - The dose-dependency of hepatic uptake and hepatobiliary transport of a drug was evaluated by means of a nonlinear least square program incorporating the finite element method, MULTI(FEM). A perfusion experiment using isolated rat livers following a pulse input (i.e., under nonsteady-state conditions) was performed at three dose levels of cefpiramide as a model drug. The hepatic extraction ratio (E(H)) of cefpiramide decreased with an increase in dose, which demonstrates that the hepatic uptake is capacity-limited. The outflow time-profiles from the liver were represented by a two-compartment dispersion model with central Michaelis Menten elimination, and the maximal elimination rate per central compartment volume (Vmax) and the Michaelis constant (Km) were estimated to be 1420 microg/ml/min and 235 microg/ml, respectively. The biliary mean transit time (t(bile)) increased slightly with an increase in dose. The hepatocellular diffusion model under non-steady-state conditions considering nonlinear transport across the bile canalicular membrane was adopted to evaluate dose-dependency in the biliary excretion of cefpiramide. The maximal penetration velocity across the bile canalicular membrane per liver (V=(bcm)max) and the affinity constant of penetration across the bile canalicular membrane (k(bcm)m = K(bcm)m A(H)L) were estimated to be 40.1 microg/min and 123 microg, respectively. Considering that the volume of a rat liver (A(H)L) is approximately 10 ml, the Michaelis constant of penetration (K(bcm)m), which is an apparent parameter, was estimated to be approximately 12.3 microg/ml. In conclusion, MULTI(FEM) is useful for evaluation of capacity-limited local disposition. PMID- 11768290 TI - A stochastic model describes the heterogeneous pharmacokinetics of cyclosporin. AB - The pharmacokinetics of cyclosporin (CsA) are unusual because of several heterogeneous features which include the presence of more than one conformer, considerable accumulation in erythrocytes and lipoproteins, extensive plasma protein binding, distribution into deep tissues, biliary secretion and hepatic clearance involving a large number of metabolites. In this study, a stochastic compartmental model was developed to describe the heterogeneous elimination kinetics of CsA. This new approach relies on a probabilistic transfer model with a gamma distributed probability intensity coefficient for drug elimination. For comparative purposes both the stochastic model and compartmental deterministic models were fitted to real post infusion data from patients receiving CsA as a 2 hr intravenous infusion. The criteria for selecting the best model showed that the stochastic model, although simpler than the compartmental deterministic models, is more flexible and gives a better fit to the kinetic data of CsA than the compartmental deterministic models. The stochastic model with a random rate intensity coefficient adequately describes the heterogeneous pharmacokinetics of CsA. PMID- 11768291 TI - Analysis of toxicokinetic data using NONMEM: impact of quantification limit and replacement strategies for censored data. AB - The purpose of this study was to examine how best to incorporate plasma samples which fall below an assay's lower limit of quantification into the process of toxicokinetic data modeling. Secondly to establish what proportion of data can be below the quantification limit without compromising NONMEM's parameter estimates. Using pharmacokinetic parameters determined in a rat toxicokinetic study we simulated datasets that might emerge from similar experiments in which only one sample was obtained per individual. A number of quantification limits were used which resulted in increasing proportions of data values being treated as if they were below the limit of quantification (BQL). For each quantification level we incorporated BQL data into our analyses in number of ways. We compared these analysis methods with respect to how well the underlying parameter values were retrieved. Omitting BQL data values or entering them as zero led to inaccurate and biased study results. We found that incorporating BQL values using more complex substitution methods via a mixed effects model produced more reliable and less biased parameter estimates. The four substitution methods that we investigated performed similarly. Parameter estimates became less reliable and more biased as the quantification level was increased depending on the method of BQL value incorporation. Naive methods of BQL data handling can produce unreliable and biased parameter estimates. An alternative is to incorporate BQL values into a population-type model, our results showed this method to be preferable. We found it advisable that the proportion of BQL data should not exceed one third and, if possible should be less than one quarter. PMID- 11768292 TI - Ways to fit a PK model with some data below the quantification limit. AB - Pharmacokinetic data consist of drug concentration measurements, as well as reports of some measured concentrations being below the quantification limit of the assay (BQL). A pharmacokinetic model may befit to these data, and for this purpose, the BQL observations must be either discarded or handled in a special way. In this paper, seven methods for dealing with BQL observations are evaluated. Both single-subject and population data are simulated from a one compartment model. A moderate amount of data is simulated for each individual. The actual cv of concentration measurements at the quantification limit is assumed to be no greater than 20%, in accord with the FDA Guidance. The results of this paper should be interpreted in this context. The methods include handling BQL observations as fixed-point censored observations, i.e., by using the likelihoods that these observations are in fact BQL. This method is shown to have some overall statistical advantage. However, the gain in using this method over that of simply discarding the BQL observations is not always much, and this is especially so when the frequency of BQL observations is small. Some simple methods entailing (i) replacing one or more BQL observations with the value 0, or (ii) replacing them with the value QL/2, where QL is the quantification limit, are also included. The first of these two approaches should not be used With population data, use of the second approach can result in some noticeably improved estimation of the typical value of a parameter, but then there is also marked degradation in the estimation of the population variance of the parameter. PMID- 11768293 TI - ATP synthases in the year 2000: evolving views about the structures of these remarkable enzyme complexes. AB - This introductory article briefly summarizes how our views about the structural features of ATP synthases (F0F1) have evolved over the past 30 years and also reviews some of our current views in the year 2000 about the structures of these remarkably unique enzyme complexes. Suffice it to say that as we approach the end of the first year of this new millinium, we can be conservatively confident that we have a reasonably good grasp of the overall "low-resolution" structural features of ATP synthases. Electron microscopy techniques, combined with the tools of biochemistry, molecular biology, and immunology, have played the leading role here by identifying the headpiece, basepiece, central stalk, side stalk, cap, and in the mitochondrial enzyme, the collar around the central stalk. We can be reasonably confident also that we have a fairly good grasp of much of the "high-resolution" structural features of both the F1 moiety comprised of fives subunit types (alpha, beta, gamma, delta, and epsilon) and parts of the F0 moiety comprised of either three (E. coli) or at least ten (mitochondria) subunit types. This information acquired in several different laboratories, either by X-ray crystallography or NMR spectroscopy, includes details about the active site and subunit relationships. Moreover, it is consistent with recently reported data that the F1 moiety may be an ATP driven motor, which, during ATP synthesis, is driven in reverse by the electrochemical proton gradient generated by the electron transport chain. The real structural challenges of the future are to acquire at high resolution "complete" ATP synthase complexes representative of different stages of the catalytic cycle during ATP synthesis and representative also of key regulatory states. PMID- 11768294 TI - F1F0-ATP synthase-stalking mind and imagination. AB - Electron microscopy together with image analysis has been used to study the structure of the intact F1F0-ATPsynthase from Escherichia coli. A procedure has been developed which allows preparation of detergent-free enzyme. Aside from the well known two-domain structure, images of F1F0 prepared by this procedure show a number of additional features, including a second stalk, which can be seen extending all the way from the F0 to the top of the F1 in some images, and a small protein on the very top of the F1, which has been identified as the delta subunit by decoration with a monoclonal antibody. In light of these results, a refined model of the subunit arrangement of the complex is presented. PMID- 11768295 TI - Structural and functional features of the Escherichia coli F1-ATPase. AB - The structural organization and overall dimensions of the Escherichia coli F1 ATPase in solution has been analyzed by synchroton X-ray scattering. Using an independent ab initio approach, the low-resolution shape of the hydrated enzyme was determined at 3.2 nm resolution. The shape permitted unequivocal identification of the volume occupied by the alpha3beta3gamma complex of the atomic model of the ECF1-ATPase. The position of the delta and epsilon subunits were found by interactive fitting of the solution scattering data and by cross linking studies. Laser-induced covalent incorporation of 2-azido-ATP established a direct relationship between nucleotide binding affinity and the different interactions between the stalk subunits gamma and epsilon with the three catalytic subunits (beta) of the F1-ATPase. Mutants of the ECF1-ATPase with the introduction of Trp-for-Tyr replacement in the catalytic site of the complex made it possible to monitor the activated state for ATP synthesis (ATP conformation) in which the gamma and epsilon subunits are in close proximity to the alpha subunits and the ADP conformation, with the stalk subunits are linked to the beta subunit. PMID- 11768296 TI - The b subunit of Escherichia coli ATP synthase. AB - The b subunit of ATP synthase is a major component of the second stalk connecting the F1 and F0 sectors of the enzyme and is essential for normal assembly and function. The 156-residue b subunit of the Escherichia coli ATP synthase has been investigated extensively through mutagenesis, deletion analysis, and biophysical characterization. The two copies of b exist as a highly extended, helical dimer extending from the membrane to near the top of F1, where they interact with the delta subunit. The sequence has been divided into four domains: the N-terminal membrane-spanning domain, the tether domain, the dimerization domain, and the C terminal delta-binding domain. The dimerization domain, contained within residues 60-122, has many properties of a coiled-coil, while the delta-binding domain is more globular. Sites of crosslinking between b and the a, alpha, beta, and delta subunits of ATP synthase have been identified, and the functional significance of these interactions is under investigation. The b dimer may serve as an elastic element during rotational catalysis in the enzyme, but also directly influences the catalytic sites, suggesting a more active role in coupling. PMID- 11768297 TI - Subunit organization of the stator part of the F0 complex from Escherichia coli ATP synthase. AB - Membrane-bound ATP synthases (F1F0) catalyze the synthesis of ATP via a rotary catalytic mechanism utilizing the energy of an electrochemical ion gradient. The transmembrane potential is supposed to propel rotation of a subunit c ring of F0 together with subunits gamma and epsilon of F1, thereby forming the rotor part of the enzyme, whereas the remainder of the F1F0 complex functions as a stator for compensation of the torque generated during rotation. This review focuses on our recent work on the stator part of the F0 complex, e.g., subunits a and b. Using epitope insertion and antibody binding, subunit a was shown to comprise six transmembrane helixes with both the N- and C-terminus oriented toward the cytoplasm. By use of circular dichroism (CD) spectroscopy, the secondary structure of subunit b incorporated into proteoliposomes was determined to be 80% alpha-helical together with 14% beta turn conformation, providing flexibility to the second stalk. Reconstituted subunit b together with isolated ac subcomplex was shown to be active in proton translocation and functional F1 binding revealing the native conformation of the polypeptide chain. Chemical crosslinking in everted membrane vesicles led to the formation of subunit b homodimers around residues bQ37 to bL65, whereas bA32C could be crosslinked to subunit a, indicating a close proximity of subunits a and b near the membrane. Further evidence for the proposed direct interaction between subunits a and b was obtained by purification of a stable ab2 subcomplex via affinity chromatography using His tags fused to subunit a or b. This ab2 subcomplex was shown to be active in proton translocation and F1 binding, when coreconstituted with subunit c. Consequences of crosslink formation and subunit interaction within the F1F0 complex are discussed. PMID- 11768298 TI - Mutagenic analysis of the F0 stator subunits. AB - The a and b subunits constitute the stator elements in the F0 sector of F1F0-ATP synthase. Both subunits have been difficult to study by physical means, so most of the information on structure and function relationships in the a and b subunits has been obtained using mutagenesis in combination with biochemical methods. These approaches were used to demonstrate that the a subunit in association with the ring of c subunits houses the proton channel through F1F0 ATP synthase. The map of the amino acids contributing to the proton channel is probably complete. The two b subunits dimerize, forming an extended flexible unit in the peripheral stalk linking the F1 and F0 sectors. The unique characteristics of specific amino acid substitutions affecting the a and b subunits suggested differential effects on rotation during F1F0-ATPase activity. PMID- 11768299 TI - Structural changes during ATP hydrolysis activity of the ATP synthase from Escherichia coli as revealed by fluorescent probes. AB - F1F0-ATPase complexes undergo several changes in their tertiary and quaternary structure during their functioning. As a possible way to detect some of these different conformations during their activity, an environment-sensitive fluorescence probe was bound to cysteine residues, introduced by site-directed mutagenesis, in the gamma subunit of the Escherichia coli enzyme. Fluorescence changes and ATP hydrolysis rates were compared under various conditions in F1 and in reconstituted F1F0. The results are discussed in terms of possible modes of operation of the ATP synthases. PMID- 11768300 TI - The Saccharomyces cerevisiae ATP synthase. AB - The ATP synthase of the yeast Saccharomyces cerevisiae is composed of 20 different subunits whose primary structure is known. The organization of proteins that constitute the membranous domain is now under investigation. Cysteine insertions combined with the use of nonpermeant maleimide reagents and cross linking reagents showing different lengths and specificity contribute to the knowledge of the location of the N- and C-termini of the subunits involved in the stator of the enzyme and their organization. This review summarizes data on yeast ATP synthase obtained in our laboratory since 1980. PMID- 11768301 TI - Partial assembly of the yeast mitochondrial ATP synthase. AB - The mitochondrial ATP synthase is a molecular motor that drives the phosphorylation of ADP to ATP. The yeast mitochondrial ATP synthase is composed of at least 19 different peptides, which comprise the F1 catalytic domain, the F0 proton pore, and two stalks, one of which is thought to act as a stator to link and hold F1 to F0, and the other as a rotor. Genetic studies using yeast Saccharomyces cerevisiae have suggested the hypothesis that the yeast mitochondrial ATP synthase can be assembled in the absence of 1, and even 2, of the polypeptides that are thought to comprise the rotor. However, the enzyme complex assembled in the absence of the rotor is thought to be uncoupled, allowing protons to freely flow through F0 into the mitochondrial matrix. Left uncontrolled, this is a lethal process and the cell must eliminate this leak if it is to survive. In yeast, the cell is thought to lose or delete its mitochondrial DNA (the petite mutation) thereby eliminating the genes encoding essential components of F0. Recent biochemical studies in yeast, and prior studies in E. coli, have provided support for the assembly of a partial ATP synthase in which the ATP synthase is no longer coupled to proton translocation. PMID- 11768302 TI - The structural and functional connection between the catalytic and proton translocating sectors of the mitochondrial F1F0-ATP synthase. AB - The structural and functional connection between the peripheral catalytic F1 sector and the proton-translocating membrane sector F0 of the mitochondrial ATP synthase is reviewed. The observations examined show that the N-terminus of subunit gamma, the carboxy-terminal and central region of F0I-PVP(b), OSCP, and part of subunit d constitute a continuous structure, the lateral stalk, which connects the peripheries of F1 to F0 and surrounds the central element of the stalk, constituted by subunits gamma and delta. The ATPase inhibitor protein (IF1) binds at one side of the F1F0 connection. The carboxy-terminal segment of IF1 apparently binds to OSCP. The 42L-58K segment of IF1, which is per se the most active domain of the protein, binds at the surface of one of the three alpha/beta pairs of F1, thus preventing the cyclic interconversion of the catalytic sites required for ATP hydrolysis. PMID- 11768303 TI - Insights into ATP synthase structure and function using affinity and site specific spin labeling. AB - A variety of different approaches has been used during the last couple of decades to investigate structure and function relationships within the catalytic portion of the F0F1-ATP synthase and of its interactions with the proton-translocator F0. In our group, we employ ESR spectroscopy with the use of stable organic radicals, so-called spin labels, as reporter groups. The radicals are either attached to substrates/ligands or specifically inserted into the protein structure by "site specific spin labeling." Both approaches bear intrinsic advantages for their special uses and result in the specific information that is available through ESR, e.g., structural changes due to binding of effector molecules (e.g., Mg2+ ions), conformational transitions during catalytic turnover, distance information on radicals bound at 20 A or less, and information on the binding characteristics of labeled substrates. This review summarizes the results of a variety of different approaches we have used during the last years to study, with the help of ESR spectroscopy, the structure of the nucleotide binding sites of F1-ATPases of different origins as well as interactions with F0 subunits. PMID- 11768304 TI - The nucleoside diphosphate kinases 1973-2000. PMID- 11768305 TI - Three-dimensional structure of nucleoside diphosphate kinase. AB - Three-dimensional structures are known from X-ray studies of the nucleoside diphosphate (NDP) kinase of many organisms from bacteria to human. All NDP kinases have subunits of about 150 residues with a very similar fold based on the alphabeta sandwich or ferredoxin fold. This fold is found in many nucleotide or polynucleotide-binding proteins with no sequence relationship to NDP kinase. This common fold is augmented here with specific features: a surface alpha-helix hairpin, the Kpn loop, and the C-terminal extension. The alpha-helix hairpin and Kpn loop make up the nucleotide binding site, which is unique to NDP kinase and different from that of other kinases or ATPases. The Kpn loop and the C-terminal extension are also involved in the quaternary structure. Whereas all known eukaryotic NDP kinases, including mitochondral enzymes, are hexamers, some bacterial enzymes are tetramers. However, hexameric and tetrameric NDP kinases are built from the same dimer. The structural environment of the active histidine is identical in all. The nucleotide binding site is also fully conserved, except for a feature implicating C-terminal residues in the hexamer, but not in the tetramer. Structural data on the native and phosphorylated enzyme, complexes with substrates, inhibitor, and a transition state analog, give a solid basis to a mechanism of phosphate transfer in which the largest contributors to catalysis are the 3'-OH of the sugar and the bound Mg2+ in the nucleotide substrate. In contrast, we still lack structural data relating to DNA binding and other functions of NDP kinases. PMID- 11768306 TI - Quaternary structure of nucleoside diphosphate kinases. AB - Nucleoside (NDP) diphosphate kinases are oligomeric enzymes. Most are hexameric, but some bacterial enzymes are tetrameric. Hexamers and tetramers are constructed by assembling identical dimers. The hexameric structure is important for protein stability, as demonstrated by studies with natural mutants (the Killer-of-prune mutant of Drosophila NDP kinase and the S120G mutant of the human NDP kinase A in neuroblastomas) and with mutants obtained by site-directed mutagenesis. It is also essential for enzymic activity. The function of the tetrameric structure is unclear. PMID- 11768307 TI - The catalytic mechanism of nucleoside diphosphate kinases. AB - Nucleoside diphosphate kinases catalyze the reversible transfer of the gamma phosphate of nucleoside triphosphates to nucleoside diphosphates. This minireview presents recent advances in understanding the reaction mechanism using steady state and fast kinetic studies, X-ray crystallography, and site-directed mutagenesis. We also briefly discuss the physiological relevance of in vitro studies. PMID- 11768309 TI - Metabolic functions of microbial nucleoside diphosphate kinases. AB - This article summarizes research from our laboratory on two aspects of the biochemistry of nucleoside diphosphate kinase from Escherichia coli--first, its interactions with several T4 bacteriophage-coded enzymes, as part of a multienzyme complex for deoxyribonucleoside triphosphate biosynthesis. We identify some of the specific interactions and discuss whether the complex is linked physically or functionally with the T4 DNA replication machinery, or replisome. Second, we discuss phenotypes of an E. coli mutant strain carrying a targeted deletion of ndk, the structural gene for nucleoside diphosphate kinase. How do bacteria lacking this essential housekeeping enzyme synthesize nucleoside triphosphates? In view of the specific interactions of nucleoside diphosphate kinase with T4 enzymes of DNA metabolism, how does T4 multiply after infection of this host? Finally, the ndk disruption strain has highly biased nucleoside triphosphate pools, including elevations of the CTP and dCTP pools of 7- and 23 fold, respectively. Accompanied by these biased nucleotide pools is a strong mutator phenotype. What is the biochemical basis for the pool abnormalities and what are the mutagenic mechanisms? We conclude with brief references to related work in other laboratories. PMID- 11768308 TI - The human Nm23/nucleoside diphosphate kinases. AB - Biochemical experiments over the past 40 years have shown that nucleoside diphosphate (NDP) kinase activity, which catalyzes phosphoryl transfer from a nucleoside triphosphate to a nucleoside diphosphate, is ubiquitously found in organisms from bacteria to human. Over the past 10 years, eight human genes of the nm23/NDP kinase family have been discovered that can be separated into two groups based on analysis of their sequences. In addition to catalysis, which may not be exhibited by all isoforms, evidence for regulatory roles has come recently from the discovery of the genes nm23 and awd, which encode NDP kinases and are involved in tumor metastasis and Drosophila development, respectively. Current work shows that the human NDP kinase genes are differentially expressed in tissues and that their products are targeted to different subcellular locations. This suggests that Nm23/NDP kinases possess different, but specific, functions within the cell, depending on their localization. The roles of NDP kinases in metabolic pathways and nucleic acid synthesis are discussed. PMID- 11768310 TI - NM23/nucleoside diphosphate kinase and signal transduction. AB - NM23s (or NDP kinases) regulate a fascinating variety of cellular activities, including proliferation, development, and differentiation. All these processes are modulated by external stimuli, leading to the idea that this family of proteins modulates transmembrane signaling pathways. This review summarizes the evidence indicating that NM23/NDP kinases participate in transmembrane signaling in eukaryotic cells and discusses the molecular mechanisms proposed to account for these actions. PMID- 11768311 TI - Human NM23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. AB - NM23-H2/NDP kinase B has been identified as a sequence-specific DNA-binding protein with affinity for a nuclease-hypersensitive element of the c-MYC gene promoter (Postel et al., 1993). The ability of Nm23-H2 to activate c-MYC transcription in vitro and in vivo via the same element demonstrates the biological significance of this interaction. Mutational analyses have identified Arg34, Asn69 and Lys135 as critical for DNA binding, but not required for the NDP kinase reaction. However, the catalytically important His118 residue is dispensible for sequence-specific DNA binding, suggesting that sequence-specific DNA recognition and phosphoryl transfer are independent properties. Nm23-H2 also has an activity that cleaves DNA site-specifically, involving a covalent protein DNA complex. In a DNA sequence-dependent manner, Nm23-H2 recognizes additional target genes for activation, including myeloperoxidase, CD11b, and CCR5, all involved in myeloid-specific differentiation. Moreover, both NM23-H1 and Nm23-H2 bind to nuclease hypersensitive elements in the platelet-derived growth factor PDGF-A gene promoter sequence-specifically, correlating with either positive or negative transcriptional regulation. These data support a model in which NM23/NDP kinase modulates gene expression through DNA binding and subsequent structural transactions. PMID- 11768312 TI - The binding mode of human nucleoside diphosphate kinase B to single-strand DNA. AB - In this paper, we studied the interaction of the human isoform B of nucleoside diphosphate kinase (NDP kinase B) with the nuclease hypersensitive element (NHE) present in the promoter element of the c-myc oncogene. The DNA-binding properties of NDP kinase B and other NDP kinases are compared and the nucleotide requirement for binding are discussed. Using quantitative methods, we identified the DNA binding sites on the protein and we proposed a structural model for a complex of one hexameric NDP kinase B with an oligonucleotide. PMID- 11768313 TI - Role of AWD/nucleoside diphosphate kinase in Drosophila development. AB - The abnormal wing discs gene of Drosophila encodes a soluble protein with nucleoside diphosphate kinase activity. This enzymic activity is necessary for the biological function of the abnormal wing discs gene product. Complete loss of function, i.e., null, mutations cause lethality after the larval stage. Most larval organs in such null mutant larvae appear to be normal, but the imaginal discs are small and incapable of normal differentiation. Killer-of-prune is a neomorphic mutation in the abnormal wing discs gene. It causes dominant lethality in larvae that lack prune gene activity. The Killer-of-prune mutant protein may have altered substrate specificity. Null mutant larvae have a low level of nucleoside diphosphate kinase activity. This suggests that there may be additional Drosophila genes that encode proteins with nucleoside dipthosphate kinase activity. Candidate genes have been found in the Drosophila genome. PMID- 11768314 TI - Nm23/nucleoside diphosphate kinase in human cancers. AB - Tumor metastasis is the leading cause of death in cancer patients. From a series of tumor cohort studies, low expression of Nm23/NDP kinase has been correlated with poor patient prognosis and survival, lymph node infiltration, and histopathological indicators of high metastatic potential in a number of cancer types, including mammary and ovarian carcinomas and melanoma. In other tumor types, no correlation has been established. Transfection of Nm23/NDP kinase cDNA into highly metastatic breast, melanoma, prostrate and squamous cell carcinomas, and colon adenocarcinoma cells significantly reduced the metastatic competency of the cells in vivo. In culture, cell motility, invasion, and colonization were inhibited, whereas tumorigenicity and cellular proliferation were not affected, indicating that Nm23/NDP kinase acts as a metastasis suppressor. PMID- 11768315 TI - Regulation of cellular functions by nucleoside diphosphate kinases in mammals. AB - The role of nucleoside diphosphate (NDP) kinases in cell growth, differentiation, and tumor metastasis in relation to signal transduction was investigated. The essential role of NDP kinase in cell growth was validated by coupling between reduced NDP kinase levels, induced by antisense oligonucleotides, and the suppression of proliferative activity of a cultured cell line. In addition, because NDP kinase levels are often enhanced with development and differentiation, as has been demonstrated in postmitotic cells and tissues, such as the heart and brain, we further examined this possibility using the bone tissue (osteoblasts) and a cultured cell line PC12D. The enhanced NDP kinase accumulation was demonstrated in the matured osteoblasts in vivo and in vitro by immunohistochemistry. In PC12D cells, neurite outgrowth took place in NDP kinase beta-transfected clones without differentiation inducers, which was accompanied by prolongation of doubling time. Neurite outgrowth, triggered by nerve growth factor and a cyclic AMP analog, was down-regulated upon forced expression of inactive mutant NDP kinase by virtue of a dominant negative effect. NDP kinase alpha-transfected rat mammary adenocarcinoma cells (MTLn3) and nm23-H2 transfected human oral squamous cell carcinoma cells (LMF4) manifested reduced metastatic potential and were associated with an altered sensitivity to environmental factors, such as motility and growth factors. NDP kinase alpha, compared to NDP kinase beta, was involved in a wide variety of the cellular phenomena examined. Taken together, NDP kinase isoforms appear to elicit both their own respective and common effects. They may have an ability to lead cells to both proliferative and differentiated states by modulating responsiveness to environmental factors, but their fate seems to depend on their surrounding milieu. PMID- 11768316 TI - Role of nucleoside diphosphate kinase in the activation of anti-HIV nucleoside analogs. AB - Nucleoside analogs are currently used in antiretrovirus therapies. The best known example is AZT one of the first drug to be used for the treatment of AIDS. However, only the triphosphate derivatives of these compounds act as substrates of the viral reverse transcriptase. Since they do not enter cells, nucleoside analogs are administered and phosphorylated by cellular kinases. The last step in this phosphorylation pathway is catalyzed by nucleoside diphosphate (NDP) kinase. The incorporation of the nucleoside triphosphates into nascent viral DNA chain results in termination of the elongation process. We have performed kinetics studies of the phosphorylation reaction by NDP kinase of dideoxynucleoside diphosphates such as 2',3'-dideoxy-3'-azidothymidine diphosphate (AZT-DP) and 2',3'-dideoxy-2',3'-didehydrothymidine diphosphate (d4T-DP). We show that the catalytic efficiency is strongly decreased and, therefore, that the reaction step catalyzed by NDP kinase constitutes a bottleneck in the processing pathway of anti-HIV compounds. In addition, the affinity of the analogs in the absence of catalysis was determined using a catalytically inactive NDP kinase mutant, showing a reduction of affinity by a factor of 2 to 30, depending on the analog. The structure of NDP kinase provides a structural explanation for these results. Indeed, all nucleoside analogs acting as chain terminators must lack a 3'-OH in the nucleotide deoxyribose. Unfortunately, this same substitution is detrimental for their capacity to be phosphorylated by NDP kinase. This defines the framework for the design of new nucleoside analogs with increased efficiency in antiretroviral therapies. PMID- 11768317 TI - New reference values for routine blood samples and human neutrophilic lipocalin during third-trimester pregnancy. AB - Reference values are usually based on blood samples from healthy men or non pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum. PMID- 11768318 TI - Evaluation of the new ImmuliteTurbo cTnI assay and the original immulite cTnI assay. AB - OBJECTIVES: An analytical and clinical evaluation of cTnI on the ImmuliteTurbo system with 15 min assay time compared to 45 min with the original Immulite assay is presented. METHODS AND DESIGN: Detection limit, functional sensitivity, AMI decision limit, assay linearity, influence of sample material (serum, heparin, citrate and EDTA plasma), interference, analytical and clinical method comparison studies were performed. RESULTS: Functional sensitivity (at CV 20%) was 0.35 compared to 0.23 microg/L for the original assay. AMI decision limit (99th percentile of a reference control group) was 0.48 microg/L for both assays. In patients with acute coronary syndromes, chronic renal failure or pulmonary embolism the assays showed concordant results in 87.2-96.5%. Differing results were only found around the cut-off level and were attributed to assay imprecision. CONCLUSION: The new assay is sensitive for the determination of cTnI, shows comparable results to the original assay version and is easy to perform within 15 min. PMID- 11768320 TI - Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium. AB - Chronic cobalt exposure is characterized by severe cardiac insufficiency. Since the mechanisms of cobalt toxicity are not yet clear, we analysed the effects of chronic cobalt exposure on antioxidant enzyme activities and myocardial mitochondrial ATP production rate in a rat model. One group of rats was fed a conventional diet and another a cobalt supplemented diet for 24 weeks. The manganese-superoxide dismutase activity was markedly reduced in the cobalt rats (18+/-4.7 U/mg protein) compared to the control rats (100+/-22 U/mg protein; p <0.001). Activity in the respiratory chain enzymes succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase was also reduced in the cobalt rats (p<0.01). Glutamate dehydrogenase activity, located in the mitochondrial matrix, was unchanged. The mitochondrial ATP production rate in relation to myocardial mass was lower in the cobalt rats for all substrates tested except palmitoyl-l-carnitine + malate. In conclusion, 24 weeks of chronic cobalt exposure induces a marked decrease in manganese-superoxide dismutase activity, a moderate decrease in mitochondrial ATP production rate and a general reduction in the capacity of the respiratory chain. The impairment in mitochondrial ATP production might be secondary to the decreased manganese superoxide dismutase activity, causing inactivation of mitochondrial factors susceptible to superoxide radicals. PMID- 11768319 TI - Characteristics of differences in Helicobacter pylori serology and 13C-urea breath-testing in an asymptomatic sample of blood donors. AB - Numerous tests, both invasive and non-invasive, are available for the diagnosis of Helicobacter pylori infection. The aim of this study was to evaluate the extent and determinants of differences in serology and 13C-urea breath test (13C UBT) in diagnosing H. pylori. Four-hundred-and-seventy-four asymptomatic blood donors aged 40 to 68 years (mean age 55.8 years) and of German nationality were recruited between October 1996 and November 1997. H. pylori infection was measured with 13C-UBT and with a commercial IgG-ELISA test (Medac; Hamburg, Germany). A standardized questionnaire was applied to identify factors which could explain discrepant results of 13C-UBT and serology. Prevalence of infection was similar according to both tests (33.1% for 13C-UBT and 30.8% for serology). From the 146 subjects with a positive serology, 121 (82.7%) had a positive 13C UBT. Previous treatment of H. pylori infection was the strongest predictor of a negative 13C-UBT given positive IgG serology (odds ratio (OR)= 12.87, 95% CI=4.10 40.36). Coffee consumption of more than 3 cups/day was also associated with an increased odds of a negative 13C-UBT given positive serology (OR = 3.12, 95% CI=1.16-8.43). No significant determinants of positive 13C-UBT given negative serology could be identified. These findings suggest a delayed fall in serum antibodies following eradication of the infection to be a major source of differences in H. pylori diagnosis using non invasive 13C-UBT and serology. PMID- 11768321 TI - Serum hepatocyte growth factor levels in patients with chronic renal disease- effect of GFR and pathogenesis. AB - Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study. levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99mTc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m2. Serum HGF levels increased slightly with decreasing GFR: the Pearson correlation coefficient being 0.49 (p<0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p=0.30). IN CONCLUSION: Serum HGF levels are correlated with GFR (for GFR > or = 5 mL/min/1.73 m2) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly. PMID- 11768322 TI - Biochemical and hemodynamic effects of ascorbic acid and alpha-tocopherol in coronary artery surgery. AB - This study was undertaken to evaluate the effects of alpha-tocopherol and ascorbic acid on markers of myocardial reperfusion injury and myocardial contractile function after coronary artery surgery. Forty-eight patients were divided into 4 groups; 300 mg/day alpha-tocopherol was given orally to the patients in group I for 14 days. In groups II and III, 4g of ascorbic acid was administered intravenously prior to induction and in the cardioplegic solution, respectively. Group IV was the control group. Blood samples were taken to determine the concentrations of creatine phosphokinase MB isoenzyme, malondialdehyde, uric acid, ascorbic acid and alpha-tocopherol in the perioperative period. Left ventricular functions were determined by means of MUGA scans and echocardiography preoperatively and on the 3rd and 7th days, postoperatively. The changes in serum creatine phosphokinase MB and malondialdehyde were significantly lower in study groups. when compared with the control group. We observed no significant changes in ventricular function, requirement for (+) inotropic agents and the incidence of ventricular arrhythmias among the groups, postoperatively. Biochemical findings are consistent with the free radical hypothesis. But we could not confirm these data with hemodynamic findings. This is probably due to the population of low-risk elective coronary surgery patients in this study. PMID- 11768323 TI - Effect of an acute oral ibuprofen intake on urinary aquaporin-2 excretion in healthy humans. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase and thereby block the prostaglandin (PG) synthesis in the kidneys. In animals, PG interferes with the formation of aquaporin 2 in the distal renal tubules. The purpose was to measure the effect of ibuprofen on urinary excretion of aquaporin 2 (u-AQP2), urinary output, urinary osmolality (u-osm) and plasma concentration of vasopressin (AVP) in a dose-response study using placebo and ibuprofen 600mg and 1200mg. In 12 healthy subjects, urine was collected in 6 periods between 07.00 h and 13.00 h, and blood samples were drawn at 60-min intervals. The study medication was given 10 h and 1 h before the study. U-AQP2 and AVP were determined by radioimmunoassays. U-AQP2 decreased 33% in the placebo group and increased 47% in the ibuprofen groups. There was a highly significant difference between the placebo group, on the one hand, and the ibuprofen groups, on the other. There was a small but significant increase in AVP in the placebo group and the 600 mg ibuprofen group, but not in the 1200 mg ibuprofen group. Urinary output was at maximum after 2 h, with a 394%, 1020% and 714% increase for placebo, 600 mg ibuprofen and 1200 mg ibuprofen, respectively. U-osm decreased during the experiment in all three groups. Inhibition of renal prostaglandin synthesis by ibuprofen affects the distal part of the nephron by increasing u AQP2. This increase was not related to changes in AVP, urinary output or urinary osmolality. We suggest that the increased excretion of AQP2 can be explained by an increase in the ratio of AQP2 that is shed into the urine because the endocytic retrieval of AQP2 from the apical membrane is impaired. This could not be revealed by changes in the osmoregulatory system by the low doses of ibuprofen used in the present study. PMID- 11768324 TI - Role of platelets and the arachidonic acid pathway in the regulation of neutrophil oxidase activity. AB - The intercellular mechanisms involved in platelet-mediated regulation of neutrophil function remain incompletely understood. This study investigated the role of the arachidonic acid pathway in the modulation of chemoattractant-induced production of oxygen metabolites, measured as luminol-amplified chemiluminescence (CL). We demonstrate that platelets dose-dependently inhibit the CL response in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Incubation with eicosatetrayonic acid (ETYA), a combined cyclooxygenase and lipooxygenase inhibitor, dramatically decreased the fMLP-induced CL response in neutrophils, an effect that was further enhanced in the presence of platelets. The separate effects of eicosatriyonic acid (ETI) and indomethacin, specific inhibitors of lipoxygenase and cyclooxygenase, respectively, were significantly lower compared to the action of ETYA. On the contrary, impediment of arachidonic acid release with the phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone (ATK) markedly increased the production of oxygen radicals triggered by fMLP. The addition of exogenous arachidonic acid clearly decreased the fMLP induced CL response in neutrophils, which further strengthens a downregulating effect of arachidonic acid on oxidase activity. This inhibitory action of arachidonic acid, however, was reversed upon co-incubation with platelets. In conclusion, this study suggests that an accumulation of arachidonic acid, following chemotactic peptide stimulation, turns off neutrophil oxidase activity. Furthermore, platelets may support the synthesis of reactive arachidonic acid metabolites, which modulate oxygen radical production in neutrophils. PMID- 11768325 TI - Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus. AB - The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival. PMID- 11768326 TI - Errors in estimating neonatal production of glucose with stable isotopes during "approximate steady state". AB - In studies of glucose metabolism in neonates, a commonly used approach is based on constant rate infusion of glucose labelled with a stable isotope in order to reach an approximate steady state with regard to isotopic enrichment in plasma. Under presumed conditions of a glucose steady state, the rates of appearance and disappearance of glucose can, in principle, be calculated with use of a simple steady-state formula. However, in the neonate, steady-state conditions do not generally prevail and results derived on such assumptions are questionable. In the present study, we have taken a pragmatic approach and compared estimates obtained from the conventional formula with values calculated with Steele's non steady-state method. The results show that the estimated glucose appearance and disappearance rates change more or less over the observed time period in all the typical cases studied, and that "steady-state estimates" may differ from the corresponding non-steady-state values by up to 37%. In a sensitivity analysis, the value of the distribution volume factor was found to be non-critical, a circumstance that supports the use of Steele's method. Thus, even though the classical Steele pool-fraction method for computation of rates of appearance and disappearance under non-steady-state conditions has been criticized, it is still the most realistic alternative to the frequently used simple steady-state formula in applications to newborns. PMID- 11768327 TI - New developments: chloroquine-resistance in Plasmodium falciparum. AB - Chloroquine-resistance is associated with higher malaria mortality in children in Africa where the drug is still widely used. In sensitive strains the drug attacks hemoglobin digestion in the lysosome and prevents detoxification of hemin to hemozoin. Reduced drug uptake is responsible for resistance, which is incompletely associated with changes in lysosome membrane protein PGH1. The report discussed here gives evidence for the role of another lysosome membrane protein, PfCRT, where a change from lysine to threonine in a transmembrane domain determines the change to resistance. Other changes in PfCRT, and to some extent change(s) in PGH1, are believed to compensate for loss of fitness of the modified PfCRT. PMID- 11768328 TI - The apicoplast as an antimalarial drug target. AB - Resistance to commonly used malaria drugs is spreading and new drugs are required urgently. The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds. The apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host thereby presenting ideal strategies for drug therapy. Indeed, many compounds targeting these plastid pathways are antimalarial and have favourable profiles based on extensive knowledge from their use as antibacterials. PMID- 11768329 TI - Cellular, pharmacokinetic, and pharmacodynamic aspects of response to camptothecins: can we improve it? AB - The camptothecins provide a novel class of effective anticancer agents that exert their action against DNA topoisomerase I. Members of the camptothecins include topotecan, irinotecan, 9-aminocamptothecin, and 9-nitrocamptothecin, which are analogs of the plant alkaloid 20(S)-camptothecin. These agents vary in their antitumor efficacy and toxicity. Several pharmacokinetic and pharmacodynamic factors including cellular efflux, modulation of topoisomerases I and II, lactone stability, alterations in metabolism, and drug-drug interactions, influence the antitumor response and toxicity of these agents. Preclinical studies suggest that protracted schedules of administration produce greater antitumor effect than bolus administration. However, the optimal treatment regimens and administration schedules of these agents have yet to be established in clinical studies. PMID- 11768330 TI - Anthracycline drug targeting: cytoplasmic versus nuclear--a fork in the road. AB - The anthracycline antibiotics doxorubicin (Adriamycin; DOX) and daunorubicin (DNR) continue to be essential components of first-line chemotherapy in the treatment of a variety of solid and hematopoietic tumors. The overall efficacies of DOX and DNR are, however, impeded by serious dose-limiting toxicities, including cardiotoxicity, and the selection of multiple mechanisms of cellular drug resistance. These limitations have necessitated the development of newer anthracyclines whose structural and functional modifications circumvent these impediments. In this review, we will present recent strategies in anthracycline design and assess their potential therapeutic merits. Current anthracycline design has diverged to target either cytoplasmic or nuclear sites. Nuclear targets have been broadened to include not only topoisomerase II (topo II) inhibition through ternary complex stabilization and catalytic inhibition, but also topoisomerase I (topo I) inhibition and transcriptional inhibition. In contrast, cytoplasmic targeting focuses on anthracycline binding to protein kinase C (PKC) regulatory domain with consequent modulation of activity. PMID- 11768331 TI - Resistance of Helicobacter pylori to antibiotics and its impact on treatment options. AB - The treatment of Helicobacter pylori infection is jeopardized by resistance to the antibiotics used, which turns out to be the main risk factor for failure. Resistance is due to point mutations. For clarithromycin only two sites in the 23S rRNA sequence are concerned and can be easily detected by molecular methods, while for metronidazole several mutations on rdxA and other genes can be responsible and so do not allow such detection. The situation for the rare cases of amoxicillin resistance is not fully determined. The impact of resistance on the clinical outcome is dramatic for clarithromycin while it only decreases the success by 20% for metronidazole. PMID- 11768332 TI - Drug resistant falciparum malaria: clinical consequences and strategies for prevention. AB - The rising prevalence of multidrug resistant falciparum malaria is occurring at an alarming rate and has serious implications for the health of many of the world's poorest countries. The dangers of not changing treatment practices immediately are huge and irreversible, threatening to both exacerbate the scale and scope of the malaria pandemic, and deprive policymakers of future options against the disease. If a health care disaster is to be avoided then massive and long term funding is urgently required. Funds need to be applied in a cohesive manner, accountable to funding bodies and tailored to the specifics of each endemic region. The key elements of such an approach should be improving early diagnosis and treatment of infection and the deployment of combination regimens containing an artemisinin derivative. These short term measures will need to be accompanied by a longer term strategy to encourage antimalarial drug research and development. PMID- 11768333 TI - Cancer research 2001: drug resistance, new targets and drug combinations. AB - The development of new anticancer drugs and the identification of novel targets represent major focus areas for pharmaceutical and biotech companies, universities and research institutes worldwide. The 92nd Annual Meeting of the American Association for Cancer Research (AACR) provided a glimpse of the latest developments in the cancer field. We highlight here presentations on resistance mechanisms (efflux, target modulation), new targets and drugs in development (topoisomerase, angiogenesis, cell cycle inhibitors) and new molecular technologies. The emergence of technologies for concurrently screening for expression of thousands of genes, has provided a new approach for the identification of molecular targets and mechanisms of both action and resistance of new compounds. The importance of inhibiting multiple targets simultaneously was brought up in several presentations. PMID- 11768339 TI - Homebound definition under the Medicare home health benefit clarified. PMID- 11768356 TI - The battle for Goose Green--the RMO's view. 1983. PMID- 11768355 TI - Bleaching discoloured teeth. AB - The bleaching of teeth has encountered some legislative problems over the past few years but it is now possible to use both vital and non-vital bleaching techniques in the UK. Hydrogen peroxide has a long history of use and would appear to be safe to use to change the appearance of discoloured teeth. It is conservative of tooth tissue and may delay the need for more invasive veneers and crowns. This article describes some of the methods of bleaching using hydrogen peroxide that are currently available. PMID- 11768357 TI - [The trend of childhood bacterial meningitis in Japan (1997.7-2000.6)]. AB - We surveyed the epidemiology of purulent meningitis in pediatrics for 3 years between July 1997 and June 2000 in Japan and obtained the following results. The number of cases of purulent meningitis was 428, which was equivalent of 1.1-1.7 children out of 1,000 hospitalized those in pediatrics per year. The age distribution for the infections was the highest under 1 year of age and it decreased as the age increased. Under 1 year of age, the highest distribution was observed in one month of age and under 1 month of age, the highest distribution was observed in 7 days of or younger ages. Haemophilus influenzae was the most common pathogen causing the infections, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. Relationship between causing pathogens and age-distribution was as follows: group B streptococcus and E. coli were major pathogens under 4 months of age and H. influenzae and S. pneumoniae were major pathogens over 3 months of age. Susceptibility tests performed at each facility demonstrated that 25.3% of H. influenzae isolates and 38.7% of S. pneumoniae isolates were drug-resistant. Analysis of resistant genes for H. influenzae and S. pneumoniae isolates, which were stored and sent, demonstrated higher rates of resistance than those observed in susceptibility tests. These results suggest that the increase in insufficient efficacy of usual treatment with combination of ampicillin and cefotaxime is predictable against the infections. Therefore, the treatment for the infections should be reconsidered. PMID- 11768358 TI - Observational evidence for an active surface reservoir of solid carbon dioxide on Mars. AB - High-resolution images of the south polar residual cap of Mars acquired in 1999 and 2001 show changes in the configuration of pits, intervening ridges, and isolated mounds. Escarpments have retreated 1 to 3 meters in 1 martian year, changes that are an order of magnitude larger than can be explained by the sublimation of water ice, but close to what is expected for sublimation of carbon dioxide ice. These observations support a 35-year-old conjecture that Mars has a large surface reservoir of solid carbon dioxide. The erosion implies that this reservoir is not in equilibrium with the present environment and that global climate change is occurring on Mars. PMID- 11768360 TI - Abstracts of the XXXVII Symposium of the Polish Histochemical and Cytochemical Society. September 2-5, 2001. Krakow, Poland. PMID- 11768359 TI - Abstracts of the 18th European Congress of the International Society of Non Invasive Cardiology. 20-22 September 2001. Krakow, Poland. PMID- 11768361 TI - University of the West Indies Medical Alumni 6th International Medical Conference. St. Kitts, November 7-11, 2001. Abstracts. PMID- 11768362 TI - An EORTC phase I study of epirubicin in combination with fixed doses of cyclophosphamide and infusional 5-fu (CEF-infu) as primary treatment of large operable or locally advanced/inflammatory breast cancer. AB - PURPOSE: The association of continuous infusion 5-fluorouracil, epirubicin (50 mg/m2 q 3 weeks) and a platinum compound (cisplatin or carboplatin) was found to be very active in patients with either locally advanced/inflammatory (LA/I) [1, 2] or large operable (LO) breast cancer (BC) [3]. The same rate of activity in terms of response rate (RR) and response duration was observed in LA/I BC patients when cisplatin was replaced by cyclophosphamide [4]. The dose of epirubicin was either 50 mg/m2 [ 1, 2, 3] or 60 mg/m2/cycle [4]. The main objective of this study was to determine the maximum tolerated dose (MTD) of epirubicin when given in combination with fixed doses of cyclophosphamide and infusional 5-fluorouracil (CEF-infu) as neoadjuvant therapy in patients with LO or LA/I BC for a maximum of 6 cycles. PATIENTS AND METHODS: Eligible patients had LO or LA/I BC, a performance status 0-1, adequate organ function and were <65 years old. Cyclophosphamide was administered at the dose of 400 mg/m2 day 1 and 8, q 4 weeks and infusional 5-fluorouracil 200 mg/m2/day was given day 1-28, q 4 weeks. Epirubicin was escalated from 30 to 45 and to 60 mg/m2 day 1 and 8; dose escalation was permitted if 0/3 or 1/6 patients experienced dose limiting toxicity (DLT) during the first 2 cycles of therapy. DLT for epirubicin was defined as febrile neutropenia, grade 4 neutropenia lasting for >7 days, grade 4 thrombocytopenia, or any non-haematological toxicity of CTC grade > or =3, excluding alopecia and plantar-palmar erythrodysesthesia (this toxicity was attributable to infusional 5-fluorouracil and was not considered a DLT of epirubicin). RESULTS: A total of 21 patients, median age 44 years (range 29-63) have been treated. 107 courses have been delivered, with a median number of 5 cycles per patient (range 4-6). DLTs on cycles I and 2 on level 1, 2, 3: grade 3 (G3) mucositis occurred in 1/10 patients treated at the third dose level. An interim analysis showed that G3 PPE occurred in 5/16 pts treated with the 28-day infusional 5-FU schedule at the 3 dose levels. The protocol was subsequently amended to limit the duration of infusional 5-fluorouracil infusion from 4 to 3 weeks. No G3 PPE was detected in 5 patients treated with this new schedule. CONCLUSIONS: This study establishes that epirubicin 60mg/m2 day 1 and 8, cyclophosphamide 400mg/m2 day 1 and 8 and infusional 5-fluorouracil 200 mg/m2/day day 1-21. q 4 weeks is the recommended dose level. Given the encouraging activity of this regimen (15/21 clinical responses) we have replaced infusional 5 fluorouracil by oral capecitabine in a recently activated study. PMID- 11768363 TI - [Doctors in Bydgoszcz 1815-1920]. AB - In the second half of the 19th century the number of Polish doctors in Pomerania increased significantly. They constituted a major group among the freelance professions within the Polish intelligentsia. The development of the Polish intelligentsia took place during a period of strong conflict between the two cultures and under increasing German influence. This was especially noticeable in Bydgoszcz which was one of the main centers of German culture in Provinz Posen. The growing wealth of the capitalistic society, as well as the development of medical science, created a greater demand for medical care. Medicine was the most liberated profession, which made it more independent from the German administration and this, in turn, made it more accessible to the Polish community. PMID- 11768364 TI - [The new cemetery in Katyn: a permanent monument to the murder of Polish officers, including pharmacists. The authors' own report]. AB - Polish army officers were called up in 1939, due to German aggression against Poland. Those who were in eastern Poland which had been occupied but the Soviet Union since September 17th 1939, were captured by the Red Army and committed to the NKVD. They were imprisoned in several camps and murdered (nearly 25.000 persons) in April and May 1940. The prisoners from the camp in Kozelsk (over 4.400 persons) were shot in Katyn forest near Smolensk. The authors went there on April 19, 2000 and were attracted by the commemorative plaques to over 60 murdered pharmacists. PMID- 11768365 TI - [The centenary of opening of the gates of medical universities to women]. AB - In the second half of the 19th century, with a wave of emancipation, women started to overcome discrimination and obtained access to the medical departments of universities. The first woman to obtain doctor's diploma was the American, Dr Elisabeth Blackwell (1821-1910) in 1851. In 1864 Switzerland was the first country in Europe to allow women to undertake medical studies. It was there that the first Polish woman - Dr Anna Tomaszewicz-Dobrska (1854-1918) obtained the doctor's diploma in 1878. In Poland, the official opening of university gates of medical faculties for women took place in 1900. In the 20s and 30s of the XXth century, the number of female doctors increased by 15%. It was then that counter feminism began in the medical profession. The process of turning the medical profession into a feminine occupation went on in spite of the counter-action which took place at that time. Nowadays it is predominantly a feminine occupation with over 50% of doctors in Poland being women. PMID- 11768366 TI - [The Knights of Malta]. AB - The Knights of Malta - an historical outline of the largest and oldest acting Christian and Maltese Order and a description of their activities in Poland and outside the country. The Maltese Order originated in the XI century, when it was founded after the conquest of Jerusalem in 1099. Its activity that time consisted of taking care of injured knights, pilgrims and the poor. Over the centuries the ideals of the order remained unchanged. Saint Jan Jerozolimski's Foundation (Maltese Help), which acts nowadays, became the executive organ of Polish Maltese Bachelors Association. It gathers volunteers and workers in the health service, nurses and people, who are not professionally connected with medicine. Those people all devote their free time and energy to those in need. The Foundation also deals with the organisation of medical sanitary services, first aid courses and providing equipment for hospitals. The Knights of Malta are still looking for young volunteers who are willing to support society. PMID- 11768367 TI - [A short history of Kartuzy's pharmacies]. AB - This paper contains a concise description of pharmacy in Kartuzy history beginning from the second half of the XIX century to the end of the Second World War. The history of a typical Pomeranian pharmacy is shown in relation to the political, social and legal changes that were taking place in Pomerania at that time. A significant part of the description concerns the period between 1919 and 1945 when one of the pharmacies "Apteka pod Orlem" was owned by a German pharmacist, Daniel Christ. PMID- 11768368 TI - [Resistance activities of the association of pharmacists in the Auschwitz Birkenau Concentration Camp]. AB - The activity of the Resistance was mainly focused on helping prisoners in the concentration camp. The underground organizations of independence existed due to the local population. That help was very effective-it rescued many people against starving and rebuilt the faith in the human. It was not only food but medicines, dressings, vaccines serums. The huge part in that help took pharmacists working in local countries and cities. This publication is strictly connected with these brave people. PMID- 11768369 TI - [Mikolaj Wodka from Kwidzyn]. AB - This paper describes the Polish physician's - Mikolaj Wodka (1442-1494) short biography. PMID- 11768370 TI - [Public health care in Poland in the Prussian Sector]. AB - Modernization processes in modern European countries, characterised by the development of contemporary organisational structures, have led to a wider range of public health and hygiene activities. New, developing ideas of public health care demonstrated the need for competent institutions, operating within national government and administration structures, capable of preventing mass epidemics and of eliminating factors from the external environment which area danger to health. These attempts were fulfilled in the beginning of the 19th century. The Prussian state and then united German empire was, at that time, a classical example for the effective organisation of self-governed public health care organisations. In the Prussian sector, public health care matters were governed by the boards of provincial, regional and district authorities. In this sector public health care was also the responsibility of sanitary commissions, which were a continuation of the earlier, so called, medical police forces. The studies devoted to the issue formulated in the title show that within the three-sector scale in partitioned Poland, the Prussian sector could serve as an example of optimal systemic solutions, not only for self-governed health care, but also for a health insurance system. These concepts were the basis for the model of public health care after 1918, in the Public state liberated from its oppressors. PMID- 11768371 TI - [Epidemic risks and their management in Lodz between 1945-1950]. AB - The sanitary and anti-epidemic activities in Lodz between 1945-1950 were characterized by a determination to maintain the good health of the citizens. At that time Lodz just like other industrial conurbations, was in a very difficult economic, social and epidemiological situation. The multisector health care system, operative at the time, which was based on organizational structures from before 1939, effectively managed the risks of epidemics. In this difficult post war period epidemics of endemic typhus, diphtheria and scarlet fever were successfully managed in Lodz, and the incidence of other acute infectious diseases decreased significantly. The sanitary conditions in the city also greatly improved. The structures of sanitary units were restored, and they in turn developed and enforced the outlines of anti-epidemic activities. The changes occurring after 1948, which aimed at the centralization of the national government, changed the range of responsibility of various institutions for the epidemiological situation in the country. PMID- 11768372 TI - Abstracts of the 9th International Symposium on Neural Regeneration. Pacific Grove, California, USA. December 12-16, 2001. PMID- 11768373 TI - Dietary antioxidants and dementia. PMID- 11768374 TI - Vitamins, trace elements, and antioxidant status in dementia disorders. AB - Antioxidants, such as vitamins C and E, have been proposed for the treatment of dementia disorders. Although other vitamins and trace elements may also have antioxidant-enhancing activities, it is not known whether the overall antioxidant status in dementia patients is associated with the intake level of these vitamins and trace elements. In this study, we assessed the levels of vitamins and trace elements in the diet of patients with Alzheimer's disease (AD), vascular dementia (VaD), and dementia with Lewy bodies (DLB) and a group of carers, along with blood levels of total antioxidant capacity (TAC). Results show that the dietary intake was decreased for most measured vitamins and trace elements in severe AD, but not in other dementia groups. In addition, we found no significant difference in the levels of TAC between any of the dementia groups. There was, however, a significant correlationbetween intake of vitamin B1, vitamin B12, zinc, and selenium and blood levels of TAC in the VaD group, but not in the AD and DLB groups. Furthermore, no association was observed in any of the dementia groups between zinc and copper intake and Cu/Zn superoxide dismutase activity, or between dietary selenium intake and glutathione peroxidase activity. The activities of these two endogenous antioxidant enzymes do not seem to be influenced by intake levels of relevant substances. The data indicate that the influence of dietary vitamins and metal ions on the overall antioxidant status is limited to VaD patients only. Clinical trials are needed to ascertain the value of antioxidant supplementation in VaD patients. PMID- 11768375 TI - Dementia with Lewy bodies treated with rivastigmine: effects on cognition, neuropsychiatric symptoms, and sleep. AB - Dementia with Lewy bodies (DLB) is a common cause of the dementia syndrome. Symptomatic treatment of the fluctuating cognition, visual hallucinations, and sleep disturbance that characterize this condition is challenging; neuroleptics are relatively contraindicated. We describe eight patients fulfilling the consensus diagnostic criteria for probable DLB who were treated with rivastigmine. Clinical features rated were: cognition by the Modified Mini-Mental State Examination (3MS); and behavioral and psychiatric symptoms by the Neuropsychiatric Inventory (NPI). Additional information was obtained from family and nursing reports. Seven patients showed resolution or improvement in cognition and neuropsychiatric symptoms as demonstrated by improvement in their 3MS and NPI scores. They also became more independent in mobility and activities of daily living, and the majority returned to live in their own home. Of the seven patients with sleep disruption, six improved. One case had no improvement in his symptomatology and the rivastigmine was stopped. Outcomes in this case series suggest that rivastigmine is well tolerated in clinical practice. PMID- 11768376 TI - Spontaneous speech of patients with dementia of the Alzheimer type and mild cognitive impairment. AB - This article discusses the potential of three assessments of language function in the diagnosis of Alzheimer-type dementia (DAT). A total of 115 patients (mean age 65.9 years) attending a memory clinic were assessed using three language tests: a picture description task (Boston Cookie-Theft picture), the Boston Naming Test, and a semantic and phonemic word fluency measure. Results of these assessments were compared with those of clinical diagnosis including the Global Deterioration Scale (GDS). The patients were classified by ICD-10 diagnosis and GDS stage as without cognitive impairment (n = 40), mild cognitive impairment (n = 34), mild DAT (n = 21), and moderate to severe DAT (n = 20). Hypotheses were (a) that the complex task of a picture description could more readily identify language disturbances than specific language tests and that (b) examination of spontaneous speech could help to identify patients with even mild forms of DAT. In the picture description task, all diagnostic groups produced an equal number of words. However, patients with mild or moderate to severe DAT described significantly fewer objects and persons, actions, features, and localizations than patients without or with mild cognitive impairment. Persons with mild cognitive impairment had results similar to those without cognitive impairment. The Boston Naming Test and both fluency measures were superior to the picture description task in differentiating the diagnostic groups. In sum, both hypotheses had to be rejected. Our results confirm that DAT patients have distinct semantic speech disturbances whereas they are not impaired in the amount of produced speech. PMID- 11768377 TI - Education bias in the mini-mental state examination. AB - Education is correlated with cognitive status assessment. Concern for test bias has led to questions of equivalent construct validity across education groups. Following the work of previous researchers, we submitted Mini-Mental State Examination (MMSE) responses to external validation analyses. Subjects were older participants in the Epidemiologic Catchment Area study (age 50-98). Little evidence for test bias against those with low education was found. The correlation of MMSE scores and age was equivalent across high- and low-education groups (-.29 vs. -.27, p = .48), as was the correlation of MMSE scores and activities of daily living (ADL) functioning (-.23 vs. -.27, p = .42). The MMSE displayed significantly higher internal consistency reliability in the low education group (.75 vs. .72, p = .04). The MMSE did not predict functional decline over 1 year or mortality over 13 years differently by level of educational attainment. Evidence for sex bias was found. The MMSE was more highly correlated with age among women than among men (-.28 vs. -.21, p < .001). The MMSE was more highly correlated with ADL impairment among women than among men ( .30 vs. -.17, p = .01). The MMSE predicted mortality differently according to participant sex (p = .053). The lack of evidence for bias provides little support to proposals to adjust MMSE scores according to level of education. PMID- 11768378 TI - The factor structure in the cognitive battery of the structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia, and dementias of other aetiology. AB - The Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, MultiInfarct Dementia, and Dementias of Other Aetiology (SIDAM) includes the Mini Mental State Examination extended by a number of additional items and allows the diagnosis of dementia according to ICD-10 and DSM-III-R criteria. The authors proposed to summarize selected items to form syndrome scores. These syndrome scores are supposed to measure different aspects of cognition. However, these syndrome scores have not been empirically confirmed. The present article presents a principal component analysis performed on the SIDAM test performances of 456 elderly subjects. The subjects were recruited in the course of a family study on dementia of the Alzheimer's type and depression in the elderly. One hundred four of these subjects met the criteria of dementia according to the ICD-10 criteria. Thus, the sample represents the population in which the SIDAM is frequently used in routine clinical and epidemiological studies. We found a six-factor structure accounting for 57.1% of the variance with some similarities to the predefined structure of different syndrome scores proposed by the authors of the SIDAM. The first factor found in principal component analysis represented different higher cortical functions that all depend on language and comprehension. Three factors covered three different aspects of memory, i.e., orientation for time, orientation for place, and short-term memory. One factor represented visuoconstructive skills and, finally, there was a factor representing intellectual abilities and education. This empirically found factor structure characterizes the dimensions of cognitive deficits in demented subjects measured by the SIDAM. Syndrome scores should reflect these dimensions. Consequently, we propose to consider the empirically found factor structure in a new version of the SIDAM. PMID- 11768379 TI - Agitation in Chinese elderly: validation of the Chinese version of the Cohen Mansfield Agitation Inventory. AB - The reliability and validity of the Chinese version of the Cohen-Mansfield Agitation Inventory (CCMAI) were studied in 164 demented patients. The agitation pattern in Chinese elderly was also examined in this study. The CCMAI demonstrated high validity, test-retest reliability, and interrater reliability. Eighty-five percent of demented patients manifested one or more agitated behaviors at least once a week. Factor analysis yielded three subtypes of agitation: physically aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors. There was a linear upward trend in physical aggression as one progressed from one Global Deterioration Scale stage to the next. Community-living patients showed higher physically nonaggressive and verbally agitated behaviors, whereas institution residents exhibited a significantly higher level of physical aggression. The differences between residential and institutionalized patients need further research. Future study should focus not only on the behavioral disturbances; medical, psychological, and environmental factors should be taken into account to provide a more accurate profile. PMID- 11768380 TI - Is a dedicated specialist social worker working exclusively with psychogeriatric inpatients and an associated dedicated domiciliary care package cost-effective? AB - BACKGROUND: The length of stay and bed usage on acute psychogeriatric admission wards are influenced by several factors. The impact of a dedicated specialist social worker working exclusively with acutely ill psychogeriatric inpatients and with a dedicated budget for domiciliary care packages on the length of stay, bed usage, and costs was evaluated in an opportunistic "before and after" cohort study. METHOD: The length of stay and bed usage for a 7-month period when a dedicated social worker and a dedicated budget for domiciliary care packages were implemented were compared with an identical 7-month period the year before. Costs incurred for extracontractual referral admissions (ECRs) were also calculated for the same periods. RESULTS: The implementation of a dedicated specialist social worker with a dedicated budget for domiciliary care packages did not demonstrate a statistically significant reduction in length of stay, but bed usage was reduced in both the local National Health Service hospital and the ECR units. The costs incurred for ECR admissions were also reduced; this reduction in costs was similar to the cost of employing a dedicated specialist social worker with the domiciliary care package. CONCLUSIONS: A dedicated specialist social worker working exclusively with psychogeriatric inpatients with a dedicated budget for domiciliary care packages was demonstrated to be cost-effective in this study. Ideally, a multicenter, randomized, and controlled study of such an intervention should be undertaken to confirm these findings. PMID- 11768381 TI - Alzheimer's disease and other dementia in nursing homes: levels of management and cost. AB - OBJECTIVE: To estimate comparative management levels and the annual cost of caring for a nursing home resident with and without dementia. METHOD: Data from the 1995 Massachusetts Medicaid nursing home database were used to examine residents with Alzheimer's disease, other types of dementia, and no dementia to determine care and dependency levels. Massachusetts Medicaid 1997 per-diem rates for each of 10 designated management levels were applied accordingly to residents in each level to estimate annual care costs. Costs from this analysis are reported in 1997 U.S. dollars. RESULTS: Of the 49,724 nursing home residents identified, 26.4% had a documented diagnosis of dementia. On average, a resident with dementia requires 229 more hours of care annually than one without dementia, resulting in a mean additional cost of $3,865 per patient with dementia per year. CONCLUSIONS: Dementia increases the care needs and cost of caring for a nursing home resident. PMID- 11768382 TI - Depression in primary care. 1: elderly patients' disclosure of depressive symptoms to their doctors. AB - BACKGROUND: This article examines some of the factors responsible for older patients' decision to report current depressive symptoms to their general medical practitioner. A companion article considers factors contributing to general practitioners' (GPs') recognition of major depressive episode when it was present. METHODS: A survey was conducted of a stratified sample of 1,021 patients aged 70+ years of 30 GPs in Melbourne, Australia, to gauge the prevalence of depressive symptoms, the frequency with which patients had informed GPs of their symptoms, and GPs' recognition of major depressive episodes. Patients and informants were questioned using the Canberra Interview for the Elderly, which generates rigorous ICD-10 research diagnoses. RESULTS: Logistic regression analysis showed that symptom disclosure was associated in descending order of importance with higher depressive scores, previous contact with a psychiatrist, and female gender. Even so, 48% of persons with ICD-10 moderate or severe depressive episode had not reported any current complaints to their doctor at the time of interview. CONCLUSION: Older patients often do not report depressive symptoms to their medical practitioner. Men and patients lacking "psychological mindedness" may be at special risk. PMID- 11768383 TI - Depression in primary care. 2: general practitioners' recognition of major depression in elderly patients. AB - BACKGROUND: It is important that serious depressive illness be recognized and treated appropriately by primary care practitioners. This and the preceding article in this issue examine (a) factors responsible for older patients' decision to report depressive symptoms to their doctor and (b) general practitioners' (GPs') recognition of depression when it was present. METHODS: A survey was conducted of a stratified sample of 1,021 patients aged 70+ years of 30 GPs in Melbourne, Australia, using the Canberra Interview for the Elderly, which generates rigorous ICD-10 research diagnoses. RESULTS: GPs' ratings of depression were best predicted in descending order of importance by patients' past contact with a psychiatrist, the doctor's view that a patient did not have dementia, the number of current depressive symptoms, patients' disclosure of these symptoms, and current physical pain. Physicians' assessments of patients' mood concurred with research diagnoses in 23 of 35 (66%) cases of ICD-10 mild depressive episode and 23 of 26 (88%) cases of moderate or severe depressive episode. GPs were unaware, however, of many depressive symptoms and often rated patients as being depressed when they were not. CONCLUSION: The use of a simple checklist of depressive symptoms would lead to a dramatic improvement in doctors' knowledge of patients' current psychiatric status. PMID- 11768384 TI - The solution structure of the viral binding domain of Tva, the cellular receptor for subgroup A avian leukosis and sarcoma virus. AB - The cellular receptor for subgroup A avian leukosis and sarcoma virus (ALSV-A) is Tva, which contains a motif related to repeats in the low density lipoprotein receptor (LDLR) ligand binding repeat (LBr) and which is necessary for viral entry. As observed with LBr repeats of LDLR, the 47 residue LBr domain of Tva (sTva47) requires calcium during oxidative folding to form the correct disulfide bonds, and calcium enhances the structure of correctly oxidized sTva47, as well as its ability to bind the viral envelope protein (Env). However, solution nuclear magnetic resonance studies indicate that, even in the presence of excess calcium, sTva47 exists in an ensemble of conformations. Nonetheless, as reported here, the structure of the predominant sTva47 solution conformer closely resembles that of other LBr repeats, with identical S-S binding topology and octahedral calcium coordination. The location of W48 and other critical residues on the surface suggests a region of the molecule necessary for Env binding and to mediate post-binding events important for ALSV-A cell entry. PMID- 11768385 TI - The Nutrition Society of Australia 25th anniversary annual scientific meeting. Canberra, Australia, 3-5 December 2001. Abstracts. PMID- 11768386 TI - Presymptomatic testing in myotonic dystrophy: genetic counselling approaches. PMID- 11768388 TI - Psychological studies in Huntington's disease: making up the balance. PMID- 11768387 TI - Trinucleotide repeat contraction: a pitfall in prenatal diagnosis of myotonic dystrophy. PMID- 11768389 TI - A novel 3' mutation in the APC gene in a family presenting with a desmoid tumour. PMID- 11768390 TI - A silent mutation in exon 14 of the APC gene is associated with exon skipping in a FAP family. PMID- 11768391 TI - Evidence of somatic mosaicism for a MECP2 mutation in females with Rett syndrome: diagnostic implications. PMID- 11768392 TI - Temperature sensitive acyl-CoA oxidase import in group A peroxisome biogenesis disorders. PMID- 11768393 TI - Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX). PMID- 11768394 TI - Maternal uniparental isodisomy 11q13qter in a dysmorphic and mentally retarded female with partial trisomy mosaicism 11q13qter. PMID- 11768395 TI - High frequencies of ICF syndrome-like pericentromeric heterochromatin decondensation and breakage in chromosome 1 in a chorionic villus sample. PMID- 11768396 TI - Supernumerary marker chromosome (1) of paternal origin and maternal uniparental disomy 1 in a developmentally delayed child. PMID- 11768397 TI - Sponastrime dysplasia: presentation in infancy. PMID- 11768398 TI - Maine asthma program links hospital resources to physician offices, schools. PMID- 11768399 TI - Hospital system tries both fast and far-reaching strategies to reduce errors. PMID- 11768400 TI - New scoring tool could take guesswork out of ovarian mass diagnosis. PMID- 11768401 TI - Clinic intervention works on depression, but will tight budgets allow it? PMID- 11768402 TI - Smoking cessation pays off right away in fewer birth complications. PMID- 11768403 TI - Aetna employs hospital report cards in fight against medical errors. PMID- 11768404 TI - Restrictive formularies counterbalanced by higher admissions, medical costs. PMID- 11768405 TI - New quality project could define, raise standards for cancer care. PMID- 11768406 TI - Patient adherence, not viral load now most important in HIV therapy. PMID- 11768407 TI - Eliminating exams before cataract surgery would save $150 million. PMID- 11768408 TI - High-dose oxygen during surgery cuts infection rates. PMID- 11768409 TI - Effectiveness of attention-deficit/hyperactivity treatment and diagnosis methods tested. PMID- 11768410 TI - Improving outcomes and reducing costs in intensive care. PMID- 11768411 TI - Improving diagnosis of degenerative joint disease of the knee by primary care physicians. PMID- 11768412 TI - Researchers urge paramedics to use artificial respiration, not intubation. PMID- 11768413 TI - Electrical stimulation of the thalamus suppresses tremor as effectively as thalamotomy. PMID- 11768414 TI - Dutch becoming first nation to legalize assisted suicide. PMID- 11768415 TI - Ethical considerations when conducting ethnographic research in a nursing home setting. AB - In this article I provide an overview of ethical concerns when conducting ethnographic research in nursing home settings where participants are vulnerable and submissive to authority, and I consider how particular research methodologies may benefit the participants. The focus of the article is primarily on the issues of privacy and autonomy and the relationship between the researcher and the participant. My own experiences of doing research in a nursing home will be woven throughout the article, as will the accounts of other researchers who have studied life in nursing homes. In reflecting on my work as a researcher I have come to a deeper understanding of the ethical issues involved in doing research in a nursing home and of the importance of ethically sound research. PMID- 11768416 TI - Critical care research and informed consent. AB - The doctrine of informed consent severely limits the ability of medical researchers to develop, evaluate, and refine investigational technologies for the treatment of patients suffering from heart attacks, strokes, and other "critical care" conditions. In this Article, Mr. Saver examines the current doctrine of informed consent as applied to critical care research and its various deficiencies. In addition, he analyzes recent reforms proposed by the Food and Drug Administration, which are intended to remove certain obstacles to critical care research posed by informed consent. While the proposed reforms address several of the current deficiencies, he asserts that they lack the breadth and scope necessary to advance the progress of critical care research in an ethical and sensible manner. Mr. Saver proposes several complementary and alternative reforms that would better accomodate the interests of all affected parties: the patients, their families, the researchers, and the general public. PMID- 11768417 TI - Traditional knowledge & contaminants project. PMID- 11768418 TI - Arctic telemedicine project. Sustainable Development Working Group, Arctic Council. PMID- 11768419 TI - Thiamine status in inhabitants of the Russian European North. PMID- 11768420 TI - Low level of serum phospholipids in inhabitants of the Russian European North. PMID- 11768421 TI - The evaluation of transferred health care services in Wunnimin Lake, Wapekeka and Kingfisher Lake First Nations: a nursing perspective. AB - The Canadian federal government initiated the policy to transfer administrative control of health services to First Nations communities in the late 1980s. While there are outstanding issues concerning the implementation of the policy, many communities consider this an opportunity to improve the health of First Nations people and the work environment of health care providers. This paper reports on the evaluation of the process of transfer of health services experienced by three communities in northwestern Ontario, Canada, focusing on nursing services. Based on interviews with health care providers and community members, the overall assessment was that transfer had successfully addressed chronic issues relating to the working conditions of nurses and problems of recruitment and retention. PMID- 11768422 TI - Alaska Natives assessing the health of their environment. AB - The changes in Alaska's ecosystems caused by pollution, contaminants and global climate change are negatively impacting Alaska Natives and rural residents who rely on natural resources for food, culture and community identity. While Alaska commerce has contributed little to these global changes and impacts, Alaska and its resources are nonetheless affected by the changes. While Alaska Natives have historically relied on Alaska's land, water and animals for survival and cultural identity, today their faith in the safety and quality of these resources has decreased. Alaska Natives no longer believe that these wild resources are the best and many are turning to alternative store-bought foods. Such a change in diet and activity may be contributing to a decline in traditional activities and a decline in general health. Contaminants are showing up in the animals, fish and waters that Alaska Natives use. Efforts need to be expanded to empower Alaska Native Tribes to collect and analyze local wild foods for various contaminants. In addition existing information on contaminants and pollution should be made readily available to Alaska residents. Armed with this type of information Alaska Native residents will be better prepared to make informed decisions on using wild foods and materials. PMID- 11768423 TI - The Alaska Native diabetes program. AB - OBJECTIVES: To provide optimum health care to indigenous people with diabetes, to prevent diabetes, and to monitor the epidemiology of diabetes and selected complications. The purposes of this paper are to describe the program and to present data that highlights the major problems and successes. STUDY DESIGN: Descriptive epidemiology report of diabetes and population service program based on yearly chart review data. METHODS: Almost half of Alaska Natives with diabetes have no direct access to physicians or hospitals. Health care delivery is now managed by the tribes themselves. Program emphases include maintenance of a population-based registry, formal training for village health aides, physical activity programs, patient education, primary prevention activities and adherence to standards of care to prevent complications. A centralized registry is maintained to assure that epidemiological data is available and patients are not lost to follow-up. Each year a random sample of charts at each major facility is audited against nationally standardized care guidelines. RESULTS: The prevalence of diabetes among Alaska Natives increased 80% over the 13 years from 1985 to 1998 (15.7/1000 to 28.3/1000, age adjusted to U.S. 1980 population). For the years 1986-1998 the incidence rates of lower extremity amputation and end stage renal disease were 6.1/1000 and 2.0/1000 respectively. The level of care provided to Alaska Native patients is comparable to that provided to the general diabetic patient population seen in Alaskan urban clinics. CONCLUSIONS: In spite of logistic challenges, care provided to Alaska Native people with diabetes compares favorably to that provided in other settings. Incidence rates of lower extremity amputation and end stage renal disease also remain comparable to or lower than those in other U.S. populations. Many aspects of our system could be extended to other chronic disease programs serving isolated indigenous populations. Primary prevention of diabetes remains a major challenge as life styles change. PMID- 11768424 TI - Why First Nations communities should not be subsumed in a rural framework: seat belt wearing rates in three Alberta First Nations communities. PMID- 11768425 TI - Cardiovascular risk factors and relatedness in an Icelandic subpopulation. AB - Theoretical and empirical studies suggest adverse effects of inbreeding on general vigour. The genetic architecture of physiological and biochemical cardiovascular risk factors is, furthermore, an unsolved issue. Our aim with this study is to investigate potential effects of inbreeding on stated risk factors in a relatively well demarcated Icelandic subpopulation. We used genealogical records to calculate coefficient of inbreeding and estimated the potential association of the coefficient with stated risk factors with known statistical methods. The results suggest absence of inbreeding depression with exception of HDL cholesterol. PMID- 11768426 TI - The cardio-vascular system in people living at latitude 65 degrees N. PMID- 11768427 TI - Adreno- and cholinoreactivity of the vascular system under the influence of low temperature. AB - The influence of low temperature results in the activation of a sympathetic division of the vegetative nervous system (mostly alpha2-artery adrenoreceptors). The data concerning the tone of the parasympathetic department are inconsistent. In studies carried out in experimental animals (rabbits), the cholinoreactivity of arterial vessels was investigated. After a single cooling the depressing action of acetylcholin on arterial vessels grows only because of an increase of the quantity of active (Pm) M-cholinoreceptors of vessels (by 66.6%) with a decrease of their sensitivity (1/K = 4) by 33.3%. By day 30 of cold depressing adaptation the action of acetylcholin grows (with doses 0.02-0.1 mkg/kg) only because of an increase of M-cholinoreceptors sensitivity by 233%. The reduction of the depressing action on arteries of acetylcholin with dozes of 0.2-0.8 mkg/kg is explained by a decrease of the quantity of active M-cholinoreceptors in these terms of the cold influence (by 41% as compared with a control group). According to the results the efficiency of the interaction (E = (Pm/2)*R)) of acetylcholin with M-cholinoreceptors of vessels grows by 96% (with E = 300 mm/m.c./1 mkg/kg in a control group up to E = 588 after 30 day's adaptation to cold). PMID- 11768428 TI - Cold air exposure and blood indices in oilers in a circumpolar area. PMID- 11768429 TI - The heliogeophysical aspects of circumpolar health. AB - With using computer database of the heliogeophysical situation during 70 years and the computer program "HELIOS" we estimate the degree of the influence of the magnetic field of the Earth at the embrional period of human organism. We carry out the express-diagnosis of magnetic sensitiveness level by means of the method of dosage magnetic loads at the time of magnetic storms. Persons with high magnetic sensitiveness (65% of the population) at the Extreme North experience the threat of the fail of stable working functional systems and developing pathologic states. The technology of their non-medicine prevention and correction were worked out. At the first time it was shown the dependence of pathological manifestations in various functional systems of human organism on expresses of the solar and magnetic activities at concrete periods of embriogeny. "Embrio heliophysical patterns" were revealed for various pathological states. The using of worked out ways of prognosis and diagnosis of the functional dependence of human organism on heliogeophysical factors in various periods of ontogeny allows not only to introduce new criteria of the selection of people at the Extreme North but also to leave to physicians exceptional abilities for prevention of many diseases. PMID- 11768430 TI - Systemic reactions of haemostasis, haemodynamics, blood lipids and thrombocyte membrane state in watch labour in the trans-polar region. AB - Various types of system reactions of men's organism to industrial migrations (Tyumen--in latitude 57 degrees north and Kharasavey in latitude 71 degrees north) and the influence of climate stress are determined. Type I reaction is characterised by a moderate increase of the watch and its subsequent normalisation. Thus the tendency to hypocoagulaemia and POL processes increase, and AOD activation of thrombocyte membranes and total phospholipids content increase in the statistically significant lysolecitin increase (p<0.05). Type II reaction is characterised by the hypertensive state for the whole period of the watch. Simultaneously with it a tendency to hypercoagulaemia, an increase of POL processes and AOD decrease of thrombocyte membranes as well as significant changes in the phospholipids spectrum with a considerable increase of lysolecitin and cardiolipin fractions are observed. Type III reaction is characterised by the development of signs of the asthenic symptocomplex, hypotonia and sleep disturbances. Thus, the tendency to hypocoagulaemia, POL processes activation and AOD decrease as well as decrease of total phospholipid content is observed. PMID- 11768431 TI - Leukogram and white blood cells count in native people of Chukotka. AB - A representative sample of male and female Chukotka natives aged 25-6 years (362 persons) has been surveyed using the cross-sectional epidemiological method. The results have been compared with the data obtained when surveying a representative sample of the non-organised population of the same age in Novosibirsk (n = 2071 persons). The mean age was 43 years. The total count of white blood cells (WBC) in peripheral blood of Chukotka natives was lower than the corresponding values of that index in the inhabitants of Novosibirsk, the 10-90% range of white blood counts being 3.0-7.0 10(9)/l in natives and 4.0-9.0 10(9)/l in residents of Novosibirsk. A significant incidence of leukopenias (<4.0 10(9)/l) has been detected, being 30% in the population of Chukotka, 24% in men and 35% in women. Modification in White Blood Cells differentials (leukogram) has been found in native Chukotka people, particularly relative and absolute lymphocytopenia. PMID- 11768432 TI - Characteristics of haematological pathology in Siberia and the North. AB - The cross-sectional epidemiological study of the female and male population aged 25-64 years and that of adolescent girls aged 13-18 years, residents of the three regions of Siberia--Mountainous Altai, Novosibirsk city and Chukotka--has detected a high prevalence of hidden, latent iron deficiency states and iron deficiency anaemias. They have been found in every third woman, every third-fifth adolescent girl of Novosibirsk and every eighth man of Chukotka. Peculiarities in risk factors of these states, including ethnically dependent ones have been detected. Leukopaenias are more frequent in Chukotka than in Novosibirsk. PMID- 11768433 TI - Melatonin secretion in SAD patients and healthy subjects matched with respect to age and sex. AB - Among the competing hypotheses concerning the aetiology of SAD is the melatonin hypothesis, which is the target of this study. 5 test subjects with SPAQ seasonality score (SS) > or = 9 and 5 controls with SS 3/4 4 participated in the study. The participants took saliva samples at home. Samples were collected 4 times a day for 3 days in March, 1999. Melatonin concentrations were determined by RIA. No significant differences in circadian rhythms were found between the groups; i.e. the curves for both groups ran parallel. However the concentrations of melatonin in the SAD patients were found to be on average 2.4 times as high as in the control group; the difference is significant at p<0.001. Our results support the melatonin hypothesis. PMID- 11768434 TI - Seasonal variation of physiological reactions in oilers working in the circumpolar area. PMID- 11768435 TI - Ecological and biochemical characteristics of alcohol pathologies in the North and their influence upon the total sickness rate of the population. AB - Studying different population groups of Yakutia and changes in statistics during the 80-90-s, this paper tries to follow up the tendencies in community differences in tolerance of human organism to alcohol. This paper is also aimed at finding out molecule-genetic reasons for the discovered differences in alcohol tolerance on the basis of research of community phenotype characteristics of isoenzyme spectrum of alcohol reducing enzymes. The paper analyses the influence of alcohol drinking intensity and population steadiness to alcohol upon somatic sickness of the number of nosologic forms and gives an assessment of mechanisms of this influence. PMID- 11768436 TI - Suicide prevention training for Aboriginal young adults with learning disabilities from Fetal Alcohol Syndrome/Fetal Alcohol Effects (FAS/FAE). PMID- 11768437 TI - Characteristics of healthy population among the migrants to the North. AB - The goal of the study was to elucidate psychophysiological characteristics of subjects who can adapt effectively to Arctic and Subarctic conditions. Plasma cortisol and insulin levels, blood pressure as well as functional sensori-motor asymmetry have been examined in the groups of North Selkups and transit workers from the Subarctic regions. The highest level of plasma cortisol was observed in the Selkups with the predominance of the right indices of sensorimotor asymmetry, whereas the lowest cortisol concentrations have been found in the left-handed groups. The level of insulin appeared to be lower in all examined groups of the Selkups. No changes in the blood pressure were found among the northern populations. The maximum incidence of arterial hypertension was revealed among shift workers with the predominance of the right profile of functional asymmetry. The indices of functional asymmetry, giving important information about adaptive abilities of different populations to severe climato-geographical conditions, can be a useful prognostic factor for the professional selection of workers in the North regions. PMID- 11768438 TI - Blood cells and hormonal and immunological parameters of humans in northeast Russia. AB - In this study the hormone and immune system parameters as well as the number of erythrocytes and hemoglobin concentration in people adapting to the northeast of Russia have been investigated. It was shown that in newcomers to the north, depending on their duration of adaptation, a specific regional norm of response in functional indices is formed which differs from parameters of the European part of the country. The number and character of correlations proved to reflect the process of functional alterations. From the structure of the correlation played the degree of human adaptation to natural and climatic extremes can be assessed. PMID- 11768439 TI - Metabolism, endocrine status, and allergy in the extreme north. AB - The problem of allergic diseases has become more and more pressing in recent years, owing to a broad prevalence and constant morbidity growth in whole world, especially in high latitude regions. The present allergy situation in polar regions, especially in active industrial assimilation centres, undoubtedly stipulates necessity of a careful analysis of its forming mechanism and a search for effective methods of prevention and correction of allergic disorders. Our studies have revealed the significant influence of ecologically stipulated endocrine status modification on frequency of allergic disorders in the north. However, the character of the immune system and liver function in the case of blood cortisol increase has not allowed us to link allergic reactions with corticosteroid production by activation of the adrenal glands. Allergies in the north are mostly dependent on the influence of insulin and thyroid hormones. As it appears, allergies occur mainly among persons with a higher insulin level. Combination of high blood insulin concentration with functional disorders of the digestive system increases the allergy frequency. A similar picture of allergy frequency dependence also emerges in thyroid hormones blood level evaluation. Generally our investigations allow us to make the conclusion that allergic disorders in migrants to northern territories are an indication of the exhaustion of the organism's reserve abilities and are mainly connected with disorders of the function of the gastrointestinal tract and liver, which are stipulated by extreme climate-geophysical conditions of the north including technogenous industrial contamination. This could probably be connected either to a reduction of gastrointestinal tract barrier function for exogenous allergens or to a decrease of metabolism velocity and the clearing of antigen substances by liver. PMID- 11768440 TI - Serum concentrations of thyroid and adrenal hormones and TSH in men after repeated 1 h-stays in a cold room. AB - We exposed six healthy men to 1-h cold air (10 degrees C) daily for 11 days and measured adrenal and thyroid hormones and TSH in serum before and after the cold air exposure on days 0, 5 and 10. We observed that on days 0, 5 and 10 the resting levels and the levels after the cold exposure in serum adrenaline, thyroid hormones and TSH did not significantly change, whereas the serum noradrenaline levels showed a significant 2.2-2.5-fold increase in response to the cold air exposures. The increases were similar indicating that the subjects did not show signs of habituation in their noradrenaline responses. Therefore the 1-h cold air exposure is not sufficiently intensive to reduce the cold-induced sympathetic response. PMID- 11768441 TI - Compensatory mechanisms of incomplete adaptation. AB - "Incomplete adaptation" (IA), as a phenomenon, is characterised by the replacement of adaptive state for compensatory physiological reactions and by the production of a suboptimal strategy of adaptation. Some laboratory investigations modulating the effect of extreme environmental factors (cold, hypoxia, shift of biological rhythms) on healthy persons as well as psychophysiological investigations of transit workers at northern plants were performed. IA is maintaining due to high plasticity of neurophysiological mechanisms of regulation, connection of central mechanisms of compensation and use of functional reserves of main homeostatic systems (cardiovascular, respiratory, oxygen-saturating, thermoregulating). The condition of IA is characterised by reactive anxiety, inversion of inter-hemisphere domination, features of psycho somatic tiredness, increased reactivity of breathing and cordial functioning, occurrences of hvpermetabolism and unstable breathing background. New correlational interactions develop between patterns of EEG-activity and indexes of breathing and cardiovascular system. Most often IA occurs when a persons activity occurs under extreme conditions, in particular, when there is a transit organization of work in the North (oil and gas complex), increasing the risk of morbidity. PMID- 11768442 TI - The role of transitive seasons on the functional status of children in the Russian European North. PMID- 11768443 TI - Development of children from urban and rural areas of West Siberia. AB - Four hundred and twenty three Slavic children aged 4-9 were tested for age sex tape related physiological features, the effects of residence (urban vs. rural), kindergarten or school establishments on physical development. The data obtained indicated that total body dimensions decreased in preschool and school age children from 1989-1999. Urban schoolchildren tended to be asthenic. Urban schoolchildren differed from the rural in their adaptation response to the standard step-test. PMID- 11768444 TI - A model for providing prenatal health care to indigenous women living in remote areas. AB - OBJECTIVE: To describe a model for providing health care services for indigenous women of childbearing age who do not have ready access to health care. STUDY DESIGN: Program description and prospective annual survey medical records. RESULTS: Measures of the success of this model of prenatal care include prenatal care initiated in the first trimester of pregnancy, low preterm birth, and low out of hospital birth. In 1985, the first year statistics were maintained, 31 percent of women entered prenatal care in their first trimester, 58 percent in their second trimester and 11 percent in their third trimester. In 1999, ninety one percent of women initiated prenatal care in their first trimester, 9 percent in their second trimester and none waited until their third trimester to initiate care. This compares favorably with Indian Health Service data indicating that in Alaska 77.4 percent of women with live births entered care in their first trimester of pregnancy. CONCLUSION: The Rural Maternal Child Health program at Alaska Native Medical Center has been successfully providing services to indigenous women and their families in 30 remote Alaska Native Villages. PMID- 11768445 TI - Longitudinal observations (1987-1997) on the prevalence of middle ear disease and associated risk factors among Inuit children of Inukjuak, Nunavik, Quebec, Canada. AB - The prevalence of middle ear disease in 2-6 year old children in 1997 was compared with that observed in 1987 in the same Inuit community in northern Quebec. Risk and protective factors associated with middle ear disease were also assessed. A total of 122 children participated. The assessments included: otological examination, cerumen sampling for analysis of organochlorine compounds, medical file review, and parent questionnaire regarding environmental and lifestyle factors. Comparison of ear examination results in 1997 and 1987 showed that there had been no change in the prevalence of chronic otitis media [9.4% to 10.8%] and proportion of ear drums with minimal scarring [45.6% to 45.4%], an increase in the proportion of normal ear drums [23.9% to 39.0%], a decrease the proportion with maximal scarring [17.8% to 2.0%] and little difference in the rate of serous otitis media [3.3% to 2.8%]. Factors found to be significantly associated with middle ear disease included: number of persons/bedroom, number of siblings with a history of ear disease, age at first, second and third visit to the nursing station for ear problems, and type of milk (formula vs. non-formula) in bottle fed children. PMID- 11768446 TI - Rapid pharmacotherapeutic intervention for an influenza A outbreak in the Canadian Arctic: lessons from the Sanikiluaq experience. AB - In January of 2000 an outbreak of influenza-like illness (ILI) was identified by Health Centre nursing staff in the remote island Inuit community of Sanikiluaq, Nunavut. A staged approach to an intervention strategy was adopted and an intervention team dispatched within 48 hours with diagnostic, prophylactic, and therapeutic capabilities and the intent to evaluate the response as well. The presence of influenza virus was determined on site in 3 out of thirteen initial cases of ILI using portable kit based rapid detection. This permitted the use of zanamivir (an inhaled neuraminidase inhibitor) for prophylaxis in 201, and for treatment in 12 persons. Amantadine was only used in 16 and 52 were ineligible for medical intervention, mostly because they fell outside of the window of opportunity or for maternal/reproductive reasons. The intervention strategy framework adopted was felt to be successful and is presented for consideration in future intervention initiatives. PMID- 11768447 TI - Bronchiolitis in Inuit children from a Canadian central arctic community, 1995 1996. AB - During the winter and summer of 1996 two outbreaks of bronchiolitis occurred among Inuit children in the Canadian arctic community of Arviat. The epidemiology and clinical features of these epidemics were studied through a chart review of bronchiolitis cases occurring from September 1, 1995 to August 31, 1996. The attack rate over the year was 57% and the incidence was 1.25 cases per child-year at risk. The median age of cases was 9 months. Children developing bronchiolitis were more likely to be male (p = 0.006). Respiratory syncytial virus (RSV) was isolated from 17 cases occurring in January/February. The hospitalization rate during those two months was 38%, mortality was 3.3%, and demands upon local health care resources were high. Parainfluenza virus type 3 was isolated from 8 cases occurring during a second smaller outbreak in July/August. Hospitalized children were more likely to be bottle-fed (p = 0.01), and duration of hospitalization was greater for RSV positive versus negative children (p = 0.002). Among those hospitalized 22% required a second admission for the same illness. Identification of prevention strategies awaits an improved understanding of the role of agent, host and environmental factors in the pathophysiology of bronchiolitis in this population. PMID- 11768448 TI - Community well being and infectious diseases among Alaska Native communities in the Chugach Region. AB - OBJECTIVES: This study sought to examine how Native people of the Chugach Region of Alaska perceive their own communities' health and well being, particularly in regard to infectious diseases. STUDY DESIGN: Prospective focus group interview survey. METHODS: During September to December 1999, 12 focus groups were conducted in seven communities in the Chugach Region of Alaska with 97 participants. Using a set of eight questions, information gathered provided insights into the participants' health-related perceptions and provided previously nonexistent baseline data pertaining toTB and hepatitis. RESULTS: Participants showed a good working knowledge of common infectious diseases. There were misconceptions and a potential for increased knowledge in highly prevalent diseases, but more recently delineated infections in rural Alaska, e.g., respiratory syncvtial virus (RSV), Helicobacter pylori, and less prevalent diseases, e.g., Acquired Immunodeficiency Syndrome (AIDS). The participants expressed a desire for further infectious disease information and dialogue. CONCLUSIONS: This process can be used to develop a risk assessment tool for medical and clinical providers' use in an effort to increase testing for such infectious diseases as HIV, TB, Hepatitis C, and sexually transmitted diseases (STDs). In this case the authors also produced a STD prevention video for rural Alaska Natives, entitled, Summer Sun Winter Moon. PMID- 11768449 TI - Zoonotic diseases: health aspects of Canadian geese. AB - OBJECTIVE: Review zoonotic diseases associated with Canadian geese. STUDY DESIGN: Review article: A review of the multiple physical, microbiologic and safety concerns, and methods used in controlling this potential problem. RESULTS: Over the last decade the Canadian goose population (protected by international treaties and protection acts) has increased rapidly such that in many cities they have become a pest rather than an admired wild bird. Their increasing numbers have caused a number of potential healthcare concerns including: physical, bacterial, parasitic, allergic and viral potential problems. The Canadian goose fecal droppings of one per minute have caused falls and the flying geese have caused air traffic accidents. Bacterial concerns, including botulism, salmonella and E. coli have all been reviewed and presented concerns. The viral Newcastle disease may be detected with hemagglutination studies and the Giardia psittaci parasites have been repeatedly found in their droppings. The Cryptosporidium parvum oocytes have been present on stool study. CONCLUSIONS: Definite links to human infectious diseases have been difficult to prove. Revision of the current laws and new control programs must be developed. PMID- 11768450 TI - Snowmobile injuries in Svalbard--a three year study [corrected]. AB - STUDY OBJECTIVE: To survey snowmobile injury events treated in Longyearbyen hospital, Svalbard and to report the injury distribution and characteristics for Svalbard residents and visitors driving snowmobiles. DESIGN: Prospective injury recording. SETTING: The Norwegian arctic archipelago, Svalbard during three years from 8 March 1997. PARTICIPANTS: The person years of the study, estimated from yearly census data on Svalbard residents, were 4211. In 1998 the number of registered snowmobiles were 1342, of which about 250 were available for use to visitors. MEASUREMENTS AND MAIN RESULTS: The variables were selected and coded according to the Nordic system. Of 107 snowmobile injuries recorded, 85 occurred during March-May (79.4%). Nine out of ten injuries occurred during leisure driving. Visitors (N=51) had peak injury frequency in the age group 30-39 and an injury rate of 68.0 per 1000 registered vehicles per year. Residents had a corresponding peak in the 20-29 age group and injury rate four times lower. The upper (23.4%) and lower (22.5%) extremities were the most commonly injured. 32 injuries were non-minor. Of these, 7 had multiple injuries. The most seriously injured had ruptured abdominal organs (spleen, kidney) or fractures of long bones. There were no fatalities. CONCLUSION: The snowmobile injury rate per 1000 registered vehicles in Svalbard is three times higher for residents (17.4) than in Swedish Lappland. The injury rate for Svalbard visitors is four times higher than the resident rate. Eight out of ten snowmobile injuries occurred during March-May. Continuous prospective hospital recording of snowmobile injuries continues in Svalbard and will enable evaluation of preventive measures targeted as a result of the present study. PMID- 11768451 TI - Bear mauling: a descriptive review. AB - OBJECTIVE: Provide a descriptive review of bear and human interactions in the United States. STUDY DESIGN: Descriptive review. RESULTS: The bear population in the United States includes the grizzly bear, the polar bear, and the black bear, including the glacier phase or blue bear. As the human population grew and remote or wilderness access improved, the bear population suffered both in total numbers and safe habitat. Conservation efforts, such as hunting restrictions and habitat enhancement, have helped to increase the total numbers of bears on the North American continent. The chance of a human encountering a bear increases as the remote bear territory diminishes. Bear incidents are widely publicized, though few serious incidents occur. The authors have direct knowledge of these bear human encounters in Alaska. Serious human injuries from black bears, or maulings, including fatalities are uncommon. Grizzly bears when trapped or stimulated may be very dangerous. The polar bear sees everything that moves or has color, as potential food, and therefore, will attack seemingly unprovoked. CONCLUSIONS: The chance of a human encountering a bear increases as the remote bear territory diminishes. Bear incidents are widely publicized, though few serious incidents occur. PMID- 11768452 TI - Improving safety in the Alaskan commercial fishing industry. AB - OBJECTIVES: Over 90% of deaths in Alaska's commercial fishing industry were due to drowning, following vessel sinkings. In the early 1990's, the U.S. Commercial Fishing Industry Vessel Safety Act required the implementation of safety measures for all fishing vessels. The purpose of our study was to examine the effectiveness of these measures in reducing the high fatality rate of Alaska's commercial fishermen. STUDY DESIGN: Alaska Occupational Injury Surveillance System and AlaskaTrauma Registry data were used to examine fishing fatalities and injuries. Demographic, risk factor, and incident data were analyzed for trend. RESULTS: During 1991-1998, there was a significant (p<0.001) (decrease in Alaskan commercial fishing deaths. Significant progress has been made in saving lives of fishermen involved in vessel sinkings. During 1991-1997, 536 fishermen suffered severe injuries (437/100,000/year). These injuries resulted from being entangled, struck or crushed by equipment (60%) and from falls (25%). CONCLUSIONS: Vessel sinkings still continue to occur, placing fishermen at substantial risk. Efforts toward improving vessel stability and hull integrity and avoidance of harsh weather conditions must be made to further reduce the fatality rate. The nature of non-fatal injuries reflect that modern fishing vessels are complex industrial environments posing multiple hazards. Measures are needed to prevent falls and improve equipment handling and machinery guarding. PMID- 11768453 TI - Alaska's model program for occupational injury prevention: applying surveillance for effective public health practice. AB - BACKGROUND: NIOSH established its Alaska Field Station in Anchorage, Alaska, in 1991, after identifying Alaska as America's highest-risk state for traumatic worker fatalities. Since then, NIOSH established comprehensive occupational injury surveillance in Alaska, and formed and facilitated interagency working groups (of state and federal agencies) and industry, labor, and professional organizations to address major factors leading to occupational death and injury in the state. STUDY DESIGN: Descriptive epidemiologic study of registry surveillance data obtained via direct on-site investigation of incidents and data sharing with jurisdictional agencies. METHODS: We established a surveillance system, obtaining information via data-sharing with jurisdictional agencies and from direct on-site investigation of incidents. Also, we collaborate with state and regional government agencies, industry, workers, and non-governmental organizations to develop interventions. RESULTS: During 1991-1999, Alaska experienced a 50-percent overall decline in work-related deaths, including a substantial decline in commercial fishing deaths, and a very sharp decline in helicopter logging-related deaths. These efforts have lead to major national and international government-industry collaborative efforts in improving the safety of helicopter lift operations, and a concomitant improvement in fishing industry mortality rates among workers fishing Alaskan seas. CONCLUSIONS: Using surveillance data as information for action, these collaborative efforts have contributed to reducing Alaska's high occupational fatality rate. This reduction has been most clearly demonstrated in the rapidly expanding helicopter logging industry. The application of surveillance data also has played an important supportive role in the substantial progress made in reducing the mortality rate in Alaska's commercial fishing industry--historically, Alaska's (and America's) most dangerous industry, and the worst killer of Alaskan workers. Results suggest that extending Alaska's approach to occupational injury surveillance and prevention to other parts of the country, and application of these strategies to the entire spectrum of occupational injury hazards, could have a broad impact on reducing occupational injuries. PMID- 11768454 TI - Micellar electrokinetic chromatography--from theoretical concepts to real samples (review). AB - Micellar electrokinetic chromatography (MEKC) is an alternative to liquid chromatographic separations. It is a highly efficient separation technique that is performed with the same experimental set-up as is used for capillary electrophoresis (CE), thus extending the applicability of CE to neutral solutes. MEKC can be regarded as a separation technique with a similar scope to that of reversed-phase high-performance liquid chromatography (RP-HPLC), having advantages over HPLC with regard to the efficiency of the separation system, separation speed, cost, and tolerance to matrix constituents. This paper discusses the applicability of MEKC to real samples and also addresses developments widening the scope of this emerging technique: on-line concentration by stacking or sweeping and sensitive detection schemes. PMID- 11768455 TI - Quality assurance in research and development: an insoluble dilemma? AB - The implementation of quality elements in research and development is a hot issue, still under discussion and development. In recent years much progress has been made in the development of effective proposals. However there are still problems and misunderstandings on how to apply quality assurance in research and development. This work clarifies these issues, mainly caused by the application of formal standards for quality assurance in R&D. It lists reasons for, and demonstrates benefits of, implementing quality elements in R&D and then offers detailed suggestions for addressing the most important issues without hampering the flexibility and creativity of R&D. PMID- 11768456 TI - Meeting the measurement uncertainty and traceability requirements of ISO/AEC standard 17025 in chemical analysis. AB - The new laboratory accreditation standard, ISO/IEC 17025, reflects current thinking on good measurement practice by requiring more explicit and more demanding attention to a number of activities. These include client interactions, method validation, traceability, and measurement uncertainty. Since the publication of the standard in 1999 there has been extensive debate about its interpretation. It is the author's view that if good quality practices are already in place and if the new requirements are introduced in a manner that is fit for purpose, the additional work required to comply with the new requirements can be expected to be modest. The paper argues that the rigour required in addressing the issues should be driven by customer requirements and the factors that need to be considered in this regard are discussed. The issues addressed include the benefits, interim arrangements, specifying the analytical requirement, establishing traceability, evaluating the uncertainty and reporting the information. PMID- 11768457 TI - Certification of the chlorine content of the isotopic reference materials IRMM 641 and IRMM-642. AB - The Slovak Institute of Metrology and the Institute for Reference Materials and Measurements have collaborated in the certification of the two chlorine reference materials IRMM-641 and IRMM-642. Until now no isotopically enriched chlorine isotopic reference material certified for isotopic composition and content has been available commercially. The isotopic reference materials IRMM-641 and IRMM 642 described herein are certified for isotopic composition and for chlorine content. The chlorine content of the reference material IRMM-641 was certified by use of high-precision argentometric coulometric titration at the Slovak Institute of Metrology. The base material used for IRMM-641 is NIST Standard Reference Material 975. The chlorine content of the reference material IRMM-642 was measured by isotope dilution, using negative thermal ionization mass spectrometry at the Institute for Reference Materials and Measurements. Both standard reference materials were prepared by dissolving NaCl in water. The reference material IRMM-641 contains 0.025022 +/- 0.00011 mol kg(-1) chlorine of natural isotopic composition with an n(37Cl)/n(35Cl) ratio of 0.31977 +/- 0.00082. The reference material IRMM-642 contains 0.004458 +/- 0.000028 mol kg(-1) chlorine with an n(37Cl)/n(35Cl) ratio of 0.01914 +/- 0.00088. PMID- 11768458 TI - Phase transfer and freezing processes investigated on acoustically levitated aqueous droplets. AB - An acoustic trap was designed and constructed to investigate, on a microscale, physicochemical processes relevant to the troposphere, mainly focusing on the temperature range below 0 degrees C. Droplets ranging from 0.5 nL to 4 microliter (0.1 to 2 mm in diameter) were introduced into the cooled reaction chamber by means of a piezo-driven micro pump with a reproducibility better than 5%. Up-take of H2O2 from the gas phase by the levitated droplet was measured and calibrated by in-situ chemiluminescence. Freezing of stably positioned droplets was observed and documented by means of a microscope and a video camera; this demonstrated the usefulness of the technique for simulation and investigation of cloud processes. Ex-situ microanalysis of sub-microliter droplets by use of a fiber optic luminometer was also shown to be a suitable means of investigating relevant physicochemical processes on a micro scale. PMID- 11768459 TI - A new calcium-sensor based on ion-selective conductometric microsensors- membranes and features. AB - Based on the concept of ion-selective conductometric microsensors (ISCOM) a new calcium sensor was developed and characterized. ISCOM have a single probe, all solid-state construction and do not need a reference electrode. These sensors are amenable to miniaturization and integration in the true sense of integrated circuit and microsystem technologies. The detection is accomplished by measurement of the bulk conductance Gm of a thin polymeric membrane containing an ion-complexing agent, where the magnitude of Gm can be related to the content of the primary ion in the analyzed solution. Thin-film platinum electrodes forming an interdigitated electrode are used as the transducer to detect the conductivity of the polymeric membrane. Optimization of the membrane composition was carried out by testing different types of calcium-ionophores, polymers, and plasticizers. The sensor characteristics have been investigated. The limit of detection is about 10(-7) mol L(-1). The dynamic range is 10(-6)-10(-1) mol L(-1) with a response time of less than 5 s. These parameters are comparable to those of corresponding potentiometric calcium selective electrodes (ISE). The Ca(2+)-ISCOM demonstrates good practical relevant selectivities against typical interfering ions for biomedical and environmental applications. PMID- 11768460 TI - Optimization of electrochemical hydride generation in a miniaturized electrolytic flow cell coupled to microwave-induced plasma atomic emission spectrometry for the determination of selenium. AB - The optimization of a continuous flow system for electrochemical hydride generation coupled to microwave-induced plasma atomic emission spectrometry (MIP AES) for the determination of Se is presented. A small electrolytic cell with a porous glassy carbon working electrode was used for hydride generation. When using an Ar MIP operated in a TE101 cavity a detection limit of 0.6 ng mL(-1) (3sigma) could be achieved. The calibration curve was linear up to 1 microgram mL(-1). A standard deviation of less than 2% (10 replicate analyses) could be achieved. It was shown that interferences of transition metals are of the same order of magnitude as with a larger electrolysis cell described earlier, and light elements hardly caused any signal depression as tested. It was possible to distinguish between Se(IV) and Se(VI) species and seleno-DL-methionine, because under optimized conditions of an electrolysis current of 10 mA, a microwave power of 210 W, an Ar flow rate of 15 L h(-1) and a sample flow rate of 2.5 mL min(-1) only Se(IV) was transformed to H2Se and transferred into the plasma. Finally, the possibility of an electrochemical pre-enrichment was shown to enable it to further decrease the detection limit. PMID- 11768461 TI - Mercury speciation by HPLC--cold-vapour radiofrequency glow-discharge optical emission spectrometry with on-line microwave oxidation. AB - Hollow-cathode (HC) radiofrequency glow-discharge (rf-GD) optical-emission spectrometry (OES) has been used as detector for the determination of inorganic mercury by cold-vapour (CV) generation in a flow-injection (FI) system. Both NaBH4 and SnCl2 were evaluated as reducing reagents for production of mercury CV. The conditions governing the discharge (pressure, He flow rate, and delivered power) and Hg CV generation (NaBH4 or SnCl2 concentration and reagent flow rate) were optimized using both reducing agents. The analytical performance characteristics of FI-CV-rf-GD-OES for mercury detection were evaluated at the 253.6 nm emission mercury line. Detection limits (DL) of 0.2 ng mL(-1) using SnCl2 and 1.8 ng mL(-1) using NaBH4 were obtained (100 microliter sample injections were used). When the optimized experimental conditions using SnCl2 had been determined, the analytical potential of this CV-rf-GD-OES method was investigated as on-line detector for high-performance liquid chromatographic (HPLC) speciation of mercury (Hg(II) and methylmercury). The HPLC-CV-rf-GD-OES detection limits for 100 microliter sample injections were found to be 1.2 and 1.8 ng mL(-1) (as mercury) of inorganic mercury and methylmercury, respectively. The reproducibility observed was below +/- 8% for both species. Finally, the HPLC CV-rf-GD-OES system developed was successfully applied to the determination of methylmercury (speciation) in two certified reference materials, Dorm-2 and Dolt 2. PMID- 11768462 TI - New tool for epidermal and cosmetic formulation studies by attenuated total reflection spectroscopy using a flexible mid-infrared fiber probe. AB - The potential of mid-infrared attenuated total-reflection spectroscopy for dermatology studies has been increased by the development of a flexible fiber optic probe from silver halide material. Such a tool significantly eases epidermal surface characterization. Spectra of human forearm skin and of bovine udder skin (BUS-model), which is used as a substitute for in-vivo tests on man, were compared, and as an example low concentrations of vitamin E acetate (alpha tocopherol acetate) in the stratum corneum were measured after topical skin application. Depth profiling was enabled by repeated steps of tape stripping and subsequent skin measurement. The infrared methodology is rapid and can be applied to small areas of skin. It is also sufficiently sensitive for analysis of a large variety of cosmetic formulations and dermatopharmaca. Discrimination of vehicle formulations is possible because of the large information content of mid-infrared spectra. PMID- 11768463 TI - Development of an ICP-HRIDMS method for accurate determination of traces of silicon in biological and clinical samples. AB - An inductively coupled plasma-high resolution isotope dilution mass spectrometric (ICP-HRIDMS) method in combination with a microwave-assisted decomposition technique has been developed for the determination of traces of silicon in biological and clinical samples. A 30Si-enriched spike solution was used for the isotope dilution step. Decomposition of the samples was achieved by use either of HNO3 or a mixture of HNO3 and HF. By application of both methods of digestion to the same sample it was possible to differentiate between a poorly soluble silicate fraction and an HNO3-soluble silicon species. Traces of silicon were determined in different reference materials, which are not certified for this element, and in other biological and clinical samples. A concentration range of 1 600 microgram g(-1) was covered by the different samples. For homogeneous samples relative standard deviations of 2-4% were obtained. The detection limit was strongly affected by the blank. In this connection purification of water, used in the analytical procedure, was especially critical. The blank contribution of the ICP-MS instrument could be minimized by applying a nebulizer and a spray chamber made of PFA, a sapphire injection tube, and a silicon nitride torch. Under these conditions detection limits of 0.15 microgram g(-1) and 0.2 microgram g(-1) were obtained for the HNO3 and HNO3-HF digestion methods, respectively, when a sample weight of 0.5 g was used. With regard to expected silicon content this enables determination in almost all biological and clinical samples. The ICP-HRIDMS results were compared with those recently obtained in an interlaboratory study. This isotope-dilution method is an potential option for certification of silicon in reference materials, a method for which is still required. PMID- 11768464 TI - Species analysis of metallothionein isoforms in human brain cytosols by use of capillary electrophoresis hyphenated to inductively coupled plasma-sector field mass spectrometry. AB - A new approach for the speciation of metallothioneins (MT) in human brain cytosols is described. The analysis is performed by application of a newly developed coupling of capillary electrophoresis (CE) with inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). Isoforms of metallothioneins are separated from 30-100 microliter sample volumes by CE and the elements Cu, Zn, Cd, and S are detected by use of ICP-SFMS. The extraction of cytosols is the first step in the analytical procedure. Tissue samples from human brain are homogenized in a buffer solution and submitted to ultra-centrifugation. The supernatant is defatted and the cytosol pre-treatment is optimized for CE separation by matrix reduction. The buffer concentration and pH used for capillary electrophoretic separation of metallothionein from rabbit liver were optimized. CE with ICP-MS detection is compared to UV detection. In the electropherograms obtained from the cytosols three peaks can be assigned to MT-1, MT-2, and MT-3. As an additional method, size-exclusion chromatography (SEC) is applied. Fractions from an SEC separation of the cytosol are collected, concentrated, and then injected into the CE. The detection of sulfur by ICP-SFMS (medium resolution mode) and quantification by isotope dilution have also been investigated as a new method for the quantification of MT isoforms. The analytical procedure developed has been used for the first time in comparative studies of the distributions of MT-1, MT-2, and MT-3 in brain samples taken from patients with Alzheimer's disease and from a control group. PMID- 11768465 TI - Two-dimensional gel electrophoresis of selenized yeast and autoradiography of 75Se-containing proteins. AB - Two-dimensional high-resolution gel electrophoresis (2DE) has been applied to the fractionation of 75Se-containing proteins in yeast, grown in 75Se-containing medium, and autoradiography was used for detection of the 75Se-containing proteins. Gel filtration and ultrafiltration were used to check whether the selenium side-chains were stable in the presence of the chemicals used for lysis and 2DE. The mass distribution of the selenium-containing proteins was estimated by use of gel filtration and the results were compared with the distribution obtained by 2DE. A 2DE map of selenium-containing proteins in yeast is presented, and compared with a total protein map of yeast. PMID- 11768466 TI - Endocrine-disrupting nonylphenols--ultra-trace analysis and time-dependent trend in mussels from the German bight. AB - A very sensitive and efficient analytical procedure is presented for the determination of 4-nonylphenols (NP) in blue mussels by use of off-line coupling of high-performance liquid chromatography (HPLC) and gas chromatography with mass spectrometric detection (GC-MS). Combined steam distillation and solvent extraction were used to extract the analytes from the mussel samples. Before quantification by GC-MS the raw extracts were purified by normal-phase HPLC. 4-n Nonylphenol was used as internal standard. The detection limit was 15 ng NP absolute, calculated from the blank value. The method was applied to the determination of NP in blue mussel samples from the German North Sea sampled over a period of 10 years. Collection, homogenization, and storage of the mussels were performed according to the Standard Operating Procedures of the German Environmental Specimen Bank since 1985. The total NP concentrations in the mussels decreased significantly from 1985 (4 microgram kg (-1)) to 1995 (1.1 microgram kg (-1)). PMID- 11768467 TI - Ibuprofen interference in the determination of 3-phenoxybenzoic acid in urine. AB - Pyrethroid insecticides are widely used in agriculture and private households. Analysis of urine for pyrethroid metabolites is one way to detect human exposure to these insecticides and is carried out regularly as part of the Occupational and Environmental Medicine Monitoring Program recommended by the Deutsche Forschungsgemeinschaft (DFG). Samples are analyzed using GC-MS (selected ion monitoring) following acid hydrolysis, solid phase extraction, esterification with methanol/sulfuric acid, and liquid-liquid extraction. The metabolite, 3 phenoxybenzoic acid (3-PBA), can be derived from several pyrethroids and is, therefore, a useful diagnostic analyte; however, the presence of the over-the counter drug, ibuprofen ((R,S)-2-(4-isobutylphenyl)propionic acid), interferes with this determination, even after the ingestion of only one 200-mg tablet. The interfering analyte is carboxy-ibuprofen which is not removed by the cleanup step. Experimental work shows that it takes two days for most of the ibuprofen to clear the body before 3-PBA can reliably be determined in urine. PMID- 11768468 TI - Is the additional greenhouse effect already evident in the current climate? AB - Several greenhouse gases, which are in part or entirely produced by human activities, have accumulated in the atmosphere since approximately the middle of the 19th century. They are assumed to have an additional greenhouse effect causing a further increase of atmospheric temperatures near the ground and a decrease in the layers above approximately 15 km altitude. The currently observed near-surface warming over nearly the entire globe is already considered by a large fraction of our society to be result of this additional greenhouse effect. Complete justification of this assumption is, however, not yet possible, because there are still too many unknowns in our knowledge of participating processes and in our modeling capabilities. PMID- 11768469 TI - Development and evaluation of a calibration gas generator for the analysis of volatile organic compounds in air based on the injection method. AB - The development and operational evaluation of a calibration gas generator for the analysis of volatile or ganic compounds (VOC) in air is described. Details of the construction, as well as of the evaluation of the apparatus are presented here. The performance of the test gas generator is validated both by on-line GC analysis of the calibration gas produced and by off-line analysis of adsorptive samples taken from the generated calibration gas. Both, active and passive sampling have been used, and the results demonstrate the excellent accuracy and precision of the generated test gas atmosphere: For the 11 investigated organic compounds (aromatic and halogenated compounds), the found values were in most cases within 5% of the target value with a reproducibility of better than 3% RSD (as determined by the analysis of the sampled adsorbent tubes). Custom made adsorbent tubes were used for active and passive sampling and in both cases were analysed by thermal-desorption GC. Particularly the combination of passive sampling and thermodesorption-GC analysis offers significant advantages over the commonly used active sampling on activated charcoal, followed by CS2 desorption in terms of avoidance of hazardous solvents, potential for automation and improved detection limits. Both sampling techniques are capable for monitoring VOCs at concentrations and under conditions relevant for workplace monitoring. PMID- 11768470 TI - Measurements of atmospheric mercury with high time resolution: recent applications in environmental research and monitoring. AB - In the past five years automated high time-resolution measurements of mercury species in ambient air have promoted remarkable progress in the understanding of the spatial distribution, short-term variability, and fate of this priority pollutant in the lower troposphere. Examples show the wide range of possible applications of these techniques in environmental research and monitoring. Presented applications of measurement methods for total gaseous mercury (TGM) include long-term monitoring of atmospheric mercury at a coastal station, simultaneous measurements during a south-to-north transect measurement campaign covering a distance of approximately 800 km, the operation on board of a research aircraft, and the quantification of mercury emissions from naturally enriched surface soils. First results obtained with a new method for the determination of reactive gaseous mercury (RGM) are presented. Typical background concentrations of TGM are between 1.5 and 2 ng m(-3) in the lower troposphere. Concentrations of RGM have been determined at a rural site in Germany between 2 and 35 pg m(-3). Flux measurements over naturally enriched surface soils in the Western U.S.A. have revealed emission fluxes of up to 200 ng Hg m(-1) h(-1) under dry conditions. PMID- 11768471 TI - Partitioning of polycyclic aromatic hydrocarbons in the polyethylene/water system. AB - The suitability of polyethylene sheets as passive samplers of lipophilic contaminants in water bodies was tested. High-density polyethylene (HDPE) and low density polyethylene (LDPE) sheets were contaminated with PAH. Uncontaminated and pre-contaminated sheets were deployed simultaneously and collected at intervals over 32 days. The exposed sheets and water samples were analyzed for PAH. The initial PAH concentrations in the contaminated and uncontaminated sheets differed by two to three orders of magnitude, but approached a common equilibrium concentration during exposure. The two- to four-ring PAH achieved quasi equilibrium within the 32-day exposure period, whereas the five- and six-ring PAH did not. The estimated PE/water partition coefficients were approximately three times higher for HDPE than for LDPE, and they were similar in magnitude to the K(ow) values (the partition coefficients between n-octanol and water). The uptake rate constants were approximately four times higher for HDPE than LDPE, which was attributed to the four times higher specific surface area. The uptake and elimination in HDPE followed linear first-order kinetics, whereas for LDPE very slow elimination rates were observed that could not be explained. The results show that PE is a simple, effective, and inexpensive material for sampling trace organic contaminants in water. PMID- 11768472 TI - An XAFS investigation of the artefacts caused by sequential extraction analyses of Pb-contaminated soils. AB - The chemical processes that occur during sequential extraction of a highly Pb contaminated soil sample were investigated using XAFS spectroscopy for the identification of the Pb species in the solid residues after each step. The sequential extraction was performed following the procedure described by Salomons and Forstner. It was found that during the sequential extraction serious alteration of the chemical binding forms of the Pb occurs. The most important processes underlying the chemical changes are the re-adsorption of solubilized Pb ions by soil matrix components and the precipitation of insoluble Pb species with anions from the extractant. PMID- 11768473 TI - Digestion of organic components in waste materials by high pressure ashing with infrared heating. AB - In respect of complete digestion of organic waste materials, a relevant potent digestion technique was developed, and a prototype of a high pressure ashing device with infrared heating (IR-HP-asher) was built. The apparatus consists of six quartz digestion vessels inside a steel autoclave. The performance of the IR HP-asher was tested for pure organic substances, for representative wastes from the recycling industry, and for several biological samples. In all cases, complete digestion could be attained within 90 min as well as complete recovery of metal(loid)s present in the sample. Concerning the completeness of digestion and absence of analyte loss, the IR-HP-asher was found to be superior to two conventional microwave digesters also tested. PMID- 11768474 TI - Chemical fractionation of a fly ash sample by a sequential leaching method. AB - A five-stage sequential leaching procedure was optimized for the analysis of the fly ash sample, CW6, as a candidate reference material. The distribution of particulate elements was achieved for Cd, Cr, Cu, Pb, Zn, and V into different fractions: (1) exchangeable, (2) bound to carbonate, (3) bound to Fe/Mn oxides, (4) bound to sulfide compounds, and (5) acid soluble, residual fraction. The leachability of the metals proved to be different, so various distribution patterns have been achieved. The results of the total elemental analysis and the sequential leaching method were compared and a good agreement was found. The uncertainty of the leaching method is reasonable, even when experimental parameters are strictly fixed and the analysis is quite tedious. The ratio of environmentally mobile fractions was compared to that from the conventional test method and a reasonable conformity has been found. This characterization method can be used to interpret the leaching behavior of element species and mode of binding to the matrix. Using the optimized sequential procedure, a new aspect can be interpreted to understand the behavior of toxic elements released from fly ashes into nature. PMID- 11768475 TI - Comparison between different leaching tests for the evaluation of metal release from fly ash. AB - Comparison of three different leaching tests, each characterized by different conditions, e.g. liquid/solid ratio, pH, leachant, stirring conditions, duration time, has been performed within the activities of Analeach, financed by the European Union in the "Cooperation with third Countries" programme (INCO). The comparison was performed on four highly homogenized fly ash reference materials, of different origin, provided by the Joint Research Centre of Ispra. Seven different elements (Cd, Cr, Cu, Ni, Pb, V, and Zn) were considered in this study. The influence of the main experimental conditions and of the matrix on metal release was studied. Basic characterization of the materials was also performed. PMID- 11768476 TI - Multi-element sewer slime impact pattern--a quantitative characteristic enabling identification of the source of heavy metal discharges into sewer systems. AB - The capability of sewer slime to accumulate heavy metals from municipal wastewater can be exploited to identify the sources of sewage sludge pollution. Former investigations of sewer slime looked for a few elements only and could, therefore, not account for deviations of the enrichment efficiency of the slime or for irregularities from sampling. Results of ICP-MS multi element determinations were analyzed by multivariate statistical methods. A new dimensionless characteristic "sewer slime impact" is proposed, which is zero for unloaded samples. Patterns expressed in this data format specifically extract the information required to identify the type of pollution and polluter quicker and with less effort and cost than hitherto. PMID- 11768477 TI - On-line flash thermodesorption-GC-MS determination of PCB in sewage sludge. AB - A flash thermodesorption-gas chromatography-mass spectrometry technique has been developed for the determination of polychlorobiphenyls (PCB), especially the highly toxic planar species, in sewage sludge. A modified Curie-point pyrolyzer was used; in this the flash-desorption temperature was controlled by selecting specific metal alloys for the pyrolysis wire. Samples (3 mg) were loaded into a quartz tube with the special heating wire wound around the outer wall. By this means rapid thermal desorption (TDS) was achieved whereas uncontrolled catalytic breakdown of the analytes was avoided. The thermodesorption unit was connected via a custom-built interface to the GC-MS detection system. The average limit of detection was 15 microgram kg(-1) sludge more than one order of magnitude better than the legal requirement. PMID- 11768478 TI - Analysis of high purity graphite and silicon carbide by direct solid sampling electrothermal atomic absorption spectrometry. AB - Solid sampling electrothermal atomic absorption spectrometry using the boat technique and a transversely heated graphite tube was applied to direct analysis of graphite and silicon carbide powders for 14 and 12 impurity elements, respectively. With graphite, for all analytes under investigation, a very effective in-situ analyte/matrix separation was achieved. That was the case also for analytes in silicon carbide requiring atomization temperatures below 2400 degrees C. At higher atomization temperatures, the decomposition products of silicon carbide give rise to significant background, which can still be corrected. Sample amounts of up to 4 mg graphite and 8 mg silicon carbide per analysis cycle were applied. For all analytes in both materials, limits of detection at the lower ng g(-1) and sub-ng g(-1) level were achieved, excluding arsenic for which they were 50 ng g(-1) and 23 ng g(-1) for graphite and silicon carbide, respectively. Quantification was performed using calibration curves measured with aqueous standard solutions. The accuracy was checked by comparison of the results with those obtained by instrumental neutron activation analysis and by other independent methods. PMID- 11768479 TI - Contribution of ICP-IDMS to the certification of antimony implanted in a silicon wafer--comparison with RBS and INAA results. AB - A thin-layer reference material for surface and near-surface analytical methods was produced and certified. The surface density of the implanted Sb layer was determined by Rutherford backscattering spectrometry (RBS), instrumental neutron activation analysis (INAA), and inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) equipped with a multi-collector. The isotopic abundances of Sb (121Sb and 123Sb) were determined by multi-collector ICP-MS and INAA. ICP IDMS measurements are discussed in detail in this paper. All methods produced values traceable to the SI and are accompanied by a complete uncertainty budget. The homogeneity of the material was measured with RBS. From these measurements the standard uncertainty due to possible inhomogeneities was estimated to be less than 0.78% for fractions of the area increments down to 0.75 mm2 in size. Excellent agreement between the results of the three different methods was found. For the surface density of implanted Sb atoms the unweighted mean value of the means of four data sets is 4.81 x 10(16) cm(-2) with an expanded uncertainty (coverage factor k = 2) of 0.09 x 10(16) cm(-2). For the isotope amount ratio R (121Sb/123Sb) the unweighted mean value of the means of two data sets is 1.435 with an expanded uncertainty (coverage factor k = 2) of 0.006. PMID- 11768480 TI - Quantification of corrosion phenomena in plastic processing machines. AB - In a model platelet system the corrosion of metallic materials was studied by processing polyethylene, polyphenylene sulfide, and glass-fibre-reinforced polyphenylene sulfide. The measurement methods used were scanning electron microscopy (images), electron-probe microanalysis (lateral element maps), secondary-ion mass spectrometry (depth profiles), X-ray photoelectron spectroscopy (chemical bonding), and grazing-incidence X-ray diffraction (structures of crystalline compounds). As nondestructive measure of corrosive attack, grazing-incidence X-ray diffraction, using the intensity ratio (IFe O/IFe), was found to be the method of choice. The reproducibility for the total procedure was found to range between 6 and 13% (rel.). The intensity ratio was examined as function of depth, of the time of stress, of material composition, and of the surrounding atmosphere. Oxides were identified as main corrosion products. The extent of oxide formation is proportional to the time elapsed after processing. PMID- 11768481 TI - Characterisation of five technical mixtures of brominated flame retardants. AB - The main components of five technical mixtures of brominated flame retardants were identified by mass spectroscopy, H-NMR, IR spectroscopy, elementary analysis, and HRGC-MS, respectively. The mixtures have been identified as: phosphoric acid bromopropylates: Bromcal P 67-6 HP; C18-alkylated bromophenols: Bromcal P 40-3; dibromopropyl-2,4,6-tribromophenyl ether: Bromcal 73-5 PE; brominated diphenyl ethers (PBrDE): Bromcal 70-5 DE; decabromodiphenyl ether: Bromcal 82-0. Gas chromatographic retention data of the various constituents were measured on standard GC columns. The data prove the interference of some of the brominated compounds with PCBs and other halogenated pesticides in HRGC using the electron capture detector. PMID- 11768482 TI - Automated flow-injection spectrophotometric determination of nitrosamines in solid food samples. AB - A spectrophotometric method using a flow-injection system is proposed for the determination of nitrosamines in foods (cured-meats). The method is based on the photochemical cleavage of the N-NO bond of the nitrosamine to yield the corresponding amine and nitrite. The nitrite is then detected spectrophotometrically, at 542 nm, by use of its reaction with a modified Griess reagent. Different linear ranges between 0.8 and 2000 ng mL(-1) are obtained for the method, depending on the time of exposure of the sample to the UV radiation. The relative standard deviation varies between 2.0 and 3.9% and the sample throughput is between three and seven samples per hour, depending on the experimental conditions. The proposed method was successfully applied to the analysis of N-nitrosodimethylamine in cured ham and loin, bacon, and sausages. PMID- 11768483 TI - When do infants know about objects? PMID- 11768484 TI - Information concentration along the boundary contours of naturally shaped solid objects. AB - In this study of the informativeness of boundary contours for the perception of natural object shape, observers viewed shadows/silhouettes cast by natural solid objects and were required to adjust the positions of a set of 10 points so that the resulting dotted shape resembled the shape of the original silhouette as closely as possible. For each object, the observers were then asked to indicate the corresponding positions of the 10 points on the original boundary contour. The results showed that there was a close correspondence between the chosen positions of the points and the locations along the boundary contour that were local curvature maxima (convexities or concavities). This finding differs from that of Kennedy and Domander (1985 Perception 14 367-370), and shows that, at least for natural objects, the original hypothesis of Attneave (1954 Psychological Review 61 183-193) is valid--local curvature maxima are indeed important for the perception of shape. PMID- 11768485 TI - The importance of being convex: an advantage for convexity when judging position. AB - Perception of contour polarity was investigated in five experiments in which observers had to judge the vertical position of a vertex. When the vertex was perceived as convex, the level of performance as measured by reaction time and errors was higher than when the same vertex was perceived as concave. I conclude that contour polarity affects how observers perceive shape, and in particular part structure, and that the position of a part is more readily available than the position of a boundary between parts. PMID- 11768486 TI - A purely temporal transparency mechanism in the visual system. AB - I report evidence for a purely temporal perceptual transparency mechanism. Rapid alternation of two images in the same location can result in the simultaneous experience of both, accompanied by a sense of transparency. This is true even when the sum of the two images does not appear transparent, which suggests that the percept is not mediated by the static transparency processes. At slow rates, alternating gratings were experienced as successive. As the rate was increased, by 8 Hz observers experienced the gratings as simultaneous. The rapidly alternating gratings are apparently processed separately before being combined for awareness by a process that integrates over about 120 ms. A final experiment tested whether the common presentation time of different parts of an image in alternation with another would cause the parts to perceptually bind. Observers did not distinguish between a rapidly alternating intact grating display and one in which halves of the display were exchanged in time. In other words, temporal binding across space did not occur. The temporal transparency phenomenon, in addition to informing theories of transparency and the dynamics of visual processing, may also be useful for the creation of transparent displays for electronic devices. PMID- 11768487 TI - The directional tuning of the barber-pole illusion. AB - In order to study the integration of local motion signals in the human visual system, we measured directional tuning curves for the barber-pole illusion by varying two crucial aspects of the stimulus layout independently across a wide a range in the same experiment. These were the orientation of the grating presented behind the rectangular aperture and the aspect ratio of the aperture, which in combination determine the relative contributions of local motion signals perpendicular to the gratings and parallel to the aperture borders, respectively. The strength of the illusion, ie the tendency to perceive motion along the major axis of the aperture, obviously depends on the spatial layout of the aperture, but also on grating orientation. Subjects were asked which direction they perceived and how compelling their motion percept was, revealing different strategies of the visual system to deal with the barber-pole stimulus. Some individuals respond strongly to the unambiguous motion information at the boundaries, leading to multistable percepts and multimodal distributions of responses. Others tend to report intermediate directions, apparently being less influenced by the actual boundaries. The general pattern of deviations from the motion direction perpendicular to grating orientation--a decrease with aspect ratio approaching unity (ie square-shaped apertures) and with gratings approaching parallel orientation to the shorter aperture boundary--is discussed in the context of simple phenomenological models of motion integration. The best fit between model predictions and experimental data is found for an interaction between two stimulus parameters: (i) cycle ratio, which is the sine-wave gratings equivalent of the terminator ratio for line gratings, describing the effects from the aperture boundaries, and (ii) the grating orientation, responsible for perpendicular motion components, which describes the influence of motion signals from inside the aperture. This suggests that the most simple cycle (terminator) ratio explanation cannot fully account for the quantitative properties of the barber-pole illusion. PMID- 11768488 TI - Visual object categorisation at distinct levels of abstraction: a new stimulus set. AB - We designed a new stimulus set with 269 line drawings of everyday artifacts and animals. The stimulus set contains several typical exemplars from a sample of 25 basic-level categories. We determined to what extent these stimuli were named at the basic level and at a more subordinate level. An additional experiment showed the validity of this calibration: typicality ratings were correlated significantly with the level of naming. In a final experiment we found that this effect depends largely on the global configuration of a stimulus as it was still apparent with degraded images obtained by locally shifting small fragments of the drawings. PMID- 11768489 TI - Carryover bias in visual assessment. AB - Carryover of stimuli in sequential judgments was studied for a visual assessment task involving estimation of the percentage cover of black circles on a white image. Seven image types with different levels of cover density were arranged in a sequentially balanced design in which each image type was preceded the same number of times by all image types. In the absence of carryover, when images were preceded by images with the same cover density, the response scores were well fitted by a power function of percentage cover with a mean exponent of 0.73 over subjects. Carryover took the form of an assimilation, so that the cover estimate for a target image was generally higher when preceded by an image with higher cover, and lower when preceded by an image with lower cover. However, the magnitude of the carryover effect showed little evidence of increasing with difference in cover between successive images. Nonparametric and parametric methods for testing for carryover are presented. The need for development of psychological models to explain the proposed statistical models is discussed. PMID- 11768490 TI - Rapid, object-based learning in the deployment of transient attention. AB - We show that transient attention summoned by an exogenous cue shows rapid learning of the relationship between the cue and a subsequent target in a discrimination task. In experiment 1, performance was unaffected when a target always appeared in the same position on a large cue, but was degraded when the target could appear anywhere within the extent of the larger cue. Experiment 2 shows that it was not the predictability of where the target appeared within the cue that aided performance, but rather a consistent location mapping of cue and target, since predictably alternating the target location relative to the cue led to worse performance than when the target was presented in the same location relative to the cue from trial to trial. Further analysis of the results of experiment 2 shows that the learning is rapid, evident after one trial, and has a cumulative influence over four consecutive trials. Possible neural correlates of this form of learning are discussed, with a focus on the supplementary eye fields in the prefrontal cortex. The reported experiments show that transient attention is not a simple reflexive mechanism but can show rapid visuospatial learning, in object-based coordinates. PMID- 11768491 TI - Quantifying the performance limits of human saccadic targeting during visual search. AB - In previous studies of saccadic targeting, the issue how visually guided saccades to unambiguous targets are programmed and executed has been examined. These studies have found different degrees of guidance for saccades depending on the task and task difficulty. In this study, we use ideal-observer analysis to estimate the visual information used for the first saccade during a search for a target disk in noise. We quantitatively compare the performance of the first saccadic decision to that of the ideal observer (ie absolute efficiency of the first saccade) and to that of the associated final perceptual decision at the end of the search (ie relative efficiency of the first saccade). Our results show, first, that at all levels of salience tested, the first saccade is based on visual information from the stimulus display, and its highest absolute efficiency is approximately 20%. Second, the efficiency of the first saccade is lower than that of the final perceptual decision after active search (with eye movements) and has a minimum relative efficiency of 19% at the lowest level of saliency investigated. Third, we found that requiring observers to maintain central fixation (no saccades allowed) decreased the absolute efficiency of their perceptual decision by up to a factor of two, but that the magnitude of this effect depended on target salience. Our results demonstrate that ideal-observer analysis can be extended to measure the visual information mediating saccadic target-selection decisions during visual search, which enables direct comparison of saccadic and perceptual efficiencies. PMID- 11768492 TI - Analysis of the effects of the delivery technique on an IMRT plan: comparison for multiple static field, dynamic and NOMOS MIMiC collimation. AB - The process of delivering an IMRT treatment may involve various beam-modifying techniques such as multileaf collimators (MLCs), the NOMOS MIMiC, blocks, wedges, etc. In the case of the MLC, the spatial/temporal variation of the position of the leaves and diaphragms in the beam allows the delivery of modulated beam profiles either by the multiple-static-field (MSF) method or by the dynamic multileaf collimator (DMLC) method. The constraints associated with the IMRT delivery technique are usually neglected in the process of obtaining the 'optimal' inverse treatment plan. Consequently, dose optimization may be significantly reduced when the 'optimal' beam profiles are converted to leaf/diaphragm positions via a leaf-sequencing interpreter. The paper presented here assesses the effects on the optimum treatment plan of the following leaf sequencing algorithms: MSF, DMLC and NOMOS MIMiC. The results obtained suggest that the delivery of an 'optimum' plan produces an overdosage of the PTV region due to various factors such as leaf/diaphragm transmission effects, head-scatter and phantom-scatter contributions. The overdosage observed for a cohort of ten patients was 2.5, 3.7 and 5.7%, respectively, for the DMLC, MSF and NOMOS MIMiC, after normalizing the delivered fluence to account for IMRT effects (using the method of Convery et al (Convery D J, Cogrove V P and Webb S 2000 Proc. 13th Int. Conf. on Computers in Radiotherapy (Heidelberg, 2000)) such as to obtain 70 Gy at the isocentre. The IMRT techniques DMLC, MIMiC and MSF were compared for the organs at risk: rectum, bladder, and left and right femoral heads. PMID- 11768493 TI - Analysis of treatment parameters for conformal shaped field stereotactic irradiation: comparison with non-coplanar arcs. AB - The change in configuration from circular convergent arcs to shaped static fields for stereotactic radiosurgery raises questions regarding comparability of dose distributions between the techniques. This study aims to quantify the optimization of planning parameters to achieve dose distributions minimizing dose to healthy tissue. Dose volume histograms were calculated and averaged from several patient treatments to measure dose homogeneity and healthy tissue irradiation inherent in variable PTV margins, the effect of increasing numbers of static shaped fields, the dose fall-off outside the PTV and of field placement. Our results show that adding a 2 mm margin around the target volume when defining field shapes maximizes dose coverage and homogeneity without substantially increasing the volume of healthy tissue irradiated to high dose levels. We demonstrate that 5-6 static fields may be optimal for typical lesions and that placement of these fields may not always play a major role in healthy tissue sparing. This work illustrates a systematic approach to conformal static field treatment plan optimization which relies on the prior determination of parameters such as optimum margin width to account for field penumbra. Complex irregularly shaped lesions still require careful patient-specific assessment of healthy tissue irradiation. PMID- 11768494 TI - Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere. AB - Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists. PMID- 11768495 TI - Determination and validation of the actual 3D temperature distribution during interstitial hyperthermia of prostate carcinoma. AB - To determine the thermal dose of a hyperthermia treatment, knowledge of the three dimensional (3D) temperature distribution is mandatory. The aim of this paper is to validate an interstitial hyperthermia treatment planning system with which the full 3D temperature distribution can be obtained in individual patients. Within a phase I study, 12 patients with prostate cancer were treated with interstitial hyperthermia using our multi electrode current source interstitial hyperthermia treatment (MECS IHT) system. The temperature distribution was measured from within the heating devices and by additional thermometry. The perfusion level was estimated and the heating implant reconstructed. The steady-state temperature distribution was calculated using our interstitial hyperthermia treatment planning system. The simulated temperature distribution was validated by individually comparing the measured and simulated thermo-sensors, both for the thermometry integrated with the heating applicators and the additional thermometry. The entire procedure was also performed on a no-flow agar-agar phantom. It was shown that the calculated temperature distribution of an individual patient during MECS interstitial hyperthermia is very heterogeneous. The validation indicates that the calculated temperature elevations match the measurements within approximately 1 degrees C. Possible improvements are more precise reconstruction, incorporation of discrete vasculature and using a temperature-dependent, heterogeneous perfusion distribution. Further technical improvements of the MECS-IHT system may also result in better temperature calculations. PMID- 11768496 TI - Interstitial ultrasound heating applicator for MR-guided thermal therapy. AB - The ability to control the shape of thermal coagulation was investigated for various interstitial heating applicators incorporating planar transducers and device rotation. Magnetic-resonance-compatible interstitial ultrasound applicators were constructed and the effects of ultrasound power, frequency, scan rate and heating time on lesion radius were studied in heating experiments in excised liver tissue. Continuous thermal lesions were generated by scanning heating applicators over a 180 angular sector. The region of thermal coagulation was restricted to the prescribed sector. Lesion radius increased with acoustic power and heating time and decreased with increasing frequency. The relationship between the temperature distribution generated by the applicator and the resulting thermal lesion was assessed with MRI. Analysis of MR temperature maps revealed that the temperature distribution could be measured accurately within 2 mm from the surface of the applicator, and the boundary of thermal coagulation was defined by a temperature of 54 +/- 12 degrees C. Calculations of temperature distributions indicated that slower scan rates can overcome the tendency of perfusion to reduce the radius of thermal lesion. This applicator design and delivery strategy make conformal interstitial heating possible. PMID- 11768497 TI - Accuracy of deconvolution analysis based on singular value decomposition for quantification of cerebral blood flow using dynamic susceptibility contrast enhanced magnetic resonance imaging. AB - Deconvolution analysis (DA) based on singular value decomposition (SVD) has been widely accepted for quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). When using this method, the elements in the diagonal matrix obtained by SVD are set to zero when they are smaller than the threshold value given beforehand. In the present study, we investigated the effect of the threshold value on the accuracy of the CBF values obtained by this method using computer simulations. We also investigated the threshold value giving the CBF closest to the assumed value (optimal threshold value) under various conditions. The CBF values obtained by this method largely depended on the threshold value. Both the mean and the standard deviation of the estimated CBF values decreased with increasing threshold value. The optimal threshold value decreased with increasing signal-to noise ratio and CBF, and increased with increasing cerebral blood volume. Although delay and dispersion in the arterial input function also affected the relationship between the estimated CBF and threshold values, the optimal threshold value tended to be nearly constant. In conclusion, our results suggest that the threshold value should be carefully considered when quantifying CBF in terms of absolute values using DSC-MRI for DA based on SVD. We believe that this study will be helpful in selecting the threshold value in SVD. PMID- 11768498 TI - Functional CT imaging of angiogenesis in rabbit VX2 soft-tissue tumour. AB - Functional parameters such as blood flow (BF), microvessel permeability surface area product (PS), blood volume (BV) and mean transit time (MTT) are physiological markers related to the changes associated with angiogenesis. In the current study we present a functional CT technique for the simultaneous measurement of these four functional parameters and the display of each parameter as a functional image over an entire tissue slice. New Zealand White rabbits with implanted VX2 thigh tumours were scanned using CT with contrast media injection. The ex vivo method of radioactive microspheres was used to evaluate the accuracy of BF measurements with the functional CT technique. There was a significant linear correlation (R = 0.96) between regional CT and microsphere-measured BF values, with a slope not significantly different from unity (0.98 +/- 0.02, P < 0.0001). The precision of our CT technique was determined by the repeated scanning under steady-state conditions. The precision of CT-measured BF, PS. BV and MTT was 14%, 18%, 20% and 24%, respectively. In conclusion, BF can be measured accurately and BF, PS, BV and MTT reproducibly using our functional CT technique. Functional CT can be readily incorporated into existing imaging protocols to assess tumour angiogenesis. PMID- 11768499 TI - Source potential mapping: a new modality to image neural electric activities. AB - A new neural electric imaging modality-source potential mapping (SPM)-is presented here, which images the neural sources by the potential produced by the sources in a homogeneous infinite conducting medium. Compared with the extant cortical surface potential mapping (CPM). SPM is a more direct reflection of the sources and is a simpler physical model, thus assuring easy understanding. The simulations show that SPM has a slightly higher spatial resolution than CPM and the calculation of SPM is more economical than that of CPM. PMID- 11768500 TI - A CCD-based optical CT scanner for high-resolution 3D imaging of radiation dose distributions: equipment specifications, optical simulations and preliminary results. AB - Methods based on magnetic resonance imaging for the measurement of three dimensional distributions of radiation dose are highly developed. However, relatively little work has been done on optical computed tomography (OCT). This paper describes a new OCT scanner based on a broad beam light source and a two dimensional charge-coupled device (CCD) detector. A number of key design features are discussed including the light source; the scanning tank, turntable and stepper motor control; the diffuser screen onto which images are projected and the detector. It is shown that the non-uniform pixel sensitivity of the low-cost CCD detector used and the granularity of the diffuser screen lead to a serious ring artefact in the reconstructed images. Methods are described for eliminating this. The problems arising from reflection and refraction at the walls of the gel container are explained. Optical ray-tracing simulations are presented for cylindrical containers with a variety of radii and verified experimentally. Small changes in the model parameters lead to large variations in the signal intensity observed in the projection data. The effect of imperfect containers on data quality is discussed and a method based on a 'correction scan' is shown to be successful in correcting many of the related image artefacts. The results of two tomography experiments are presented. In the first experiment, a radiochromic Fricke gel sample was exposed four times in different positions to a 100 kVp x ray beam perpendicular to the plane of imaging. Images of absorbed dose with slice thickness of 140 microm were acquired. with 'true' in-plane resolution of 560 x 560 microm2 at the edge of the 72 mm field of view and correspondingly higher resolution at the centre. The nominal doses measured correlated well with the known exposure times. The second experiment demonstrated the well known phenomenon of diffusion in the dosemeter gels and yielded a value of (0.12 +/- 0.02) mm2 s(-1) for the diffusion coefficient of the xylenol orange/iron complex. Finally, the overall implications of the above findings for dosimetry using OCT are discussed. PMID- 11768501 TI - Photon scatter kernels for intensity modulating radiation therapy filters. AB - The most important beam property while optimizing photon therapy is the ability to modulate the intensity of the beam. The use of photon absorbers for intensity modulation of beam profiles requires special attention to be paid to the alteration of beam properties due to scatter and spectral changes, in addition to the desired intensity modulation. In this study the influence of photon scatter in high-density filters irradiated with very narrow photon pencil beams was investigated. A simple analytical relation is developed to quantify the contribution by scattered photons. A scatter kernel was derived by convolving the first Compton scatter distribution with an approximate expression for the second order scattered photons. The calculations were validated experimentally with film dosimetry and also by using Monte Carlo simulations. Results show that the difference in photon scatter estimation by different methods is relatively small when higher order scattering is accounted for. At 6 MV x-rays the agreement is slightly better than that for 18 MV x-rays results. The simple relation presented in this paper can be used to account for the scattered photon contribution in filter optimization codes to deliver biologically or physically optimized intensity modulated treatments. PMID- 11768502 TI - Optimization of intensity modulated radiotherapy under constraints for static and dynamic MLC delivery. AB - Multi-leaf collimators (MLCs) are emerging as the prevalent modality to apply intensity modulated radiotherapy (IMRT). Both the principle and the particular design of MLCs stipulate complex constraints on the practically applicable intensity modulated radiation fields. Most consequentially, the distribution of exposure times across the maximum field outline is either a piecewise constant function in the static mode or a piecewise linear function in the dynamic mode of driving an MLC. In view of clinical utility, the total leaf movement should be minimized, which requires that MLC-related constraints be considered in the dose optimization process. A method is proposed to achieve this for both static MLC fields and dynamic leaf close-in application. The method is an amendment to a generic gradient-based IMRT dose optimization algorithm and solves numerical problems related to the non-convexity of the MLC constraints, which can cause erratic behaviour of a gradient-based algorithm. It employs bistable penalty functions to select preferrable leaf configurations from the configuration space of the MLC, which is limited by specific design features. Together with an 'annealing' escape mechanism from local minima, the algorithm is capable of finding the optimum of an IMRT problem as leaf sequences with minimized leaf travel. In particular, the efficiency of static IMRT can be raised to the levels of unmodulated fields with very few field segments, thereby increasing the utility of IMRT in clinical practice. PMID- 11768504 TI - The relative response of NE2561 and NE2611A ionization chambers in megavoltage x ray beams. AB - The relative energy response of NE2561 and NE261 IA ionization chambers to megavoltage photon beams from the ARPANSA linac indicates significant differences between these two types of chamber. In 16 MV beams of TPR20(10) 0.779, differences of about 2% are observed. The results are expressed as ratios KQ of the beam quality correction factors kQ, where the kQ factor for each type of chamber is the ratio of the absorbed dose to water calibration factor ND, at the x-ray quality Q to that at 60Co. These results have implications for the use of generic kQ factors in dosimetry protocols and suggest that NE2561 and NE2611A ionization chambers cannot be assumed to be identical. PMID- 11768503 TI - Monte Carlo simulation of a dynamic MLC based on a multiple source model. AB - Detailed knowledge of the characteristics of the radiation field shaped by a multileaf collimator (MLC) is essential in intensity modulated radiotherapy (IMRT). A previously developed multiple source model (MSM) for a 6 MV beam was extended to a 15 MV beam and supplemented with an accurate model of an 80-leaf dynamic MLC. Using the supplemented MSM and the MC code GEANT, lateral dose distributions were calculated in a water phantom and a portal water phantom. A field which is normally used for the validation of the step and shoot technique and a field from a realistic IMRT treatment plan delivered with dynamic MLC are investigated. To assess possible spectral changes caused by the modulation of beam intensity by an MLC, the energy spectra in five portal planes were calculated for moving slits of different widths. The extension of the MSM to 15 MV was validated by analysing energy fluences, depth doses and dose profiles. In addition, the MC-calculated primary energy spectrum was verified with an energy spectrum which was reconstructed from transmission measurements. MC-calculated dose profiles using the MSM for the step and shoot case and for the dynamic MLC case are in very good agreement with the measured data from film dosimetry. The investigation of a 13 cm wide field shows an increase in mean photon energy of up to 16% for the 0.25 cm slit compared to the open beam for 6 MV and of up to 6% for 15 MV, respectively. In conclusion, the MSM supplemented with the dynamic MLC has proven to be a powerful tool for investigational and benchmarking purposes or even for dose calculations in IMRT. PMID- 11768505 TI - Validation of the scanning -gamma-ray telescope for in vivo dosimetry and boron measurements during BNCT. AB - Gamma-ray telescope scans of a box phantom with inhomogeneous boron concentrations have proven the feasibility of in vivo measurements of different boron distributions in the head of a patient during boron neutron capture therapy (BNCT). Small structures with enhanced boron concentration can be reconstructed in a head phantom, even if the brain compartment of the phantom is surrounded by a skin layer with a ten times higher boron concentration. The motor-controlled telescope can scan the head/phantom, detecting boron and hydrogen prompt y-rays emitted at neutron capture reactions with a two-dimensional spatial resolution of 14 mm full width at half maximum. For reconstruction of the boron concentrations from the measured y-ray detection rates, a mathematical reconstruction algorithm is derived and discussed. Proper reconstruction requires position-dependent y-ray measurements combined with treatment planning programme calculations of the thermal neutron distribution. In a head phantom, in which the brain and the skull (bulk) were represented using a homogeneous boron distribution of 5.2 +/- 0.5 ppm 10B, surrounded by a skin layer with a ten times higher boron concentration, the bulk concentration was reconstructed to 4.7 +/- 0.3 ppm 10B. Telescope scans along and perpendicular to the beam axis showed the influence of inhomogeneities with a high boron concentration such as skin and a simulated blood vessel, respectively with a low boron concentration such as white matter. The profiles of the boron and hydrogen y-ray detection rates indicate how future patient measurements can be interpreted. In clinical trials, the telescope can then be used to investigate the averaged boron concentration in the bulk of a patient and local enhanced boron concentrations (e.g. in tumour tissue) in order to relate the measured boron dose distributions to the clinical effects of BNCT. Simultaneously, it can serve as quality control of the dosimetry during the irradiation. PMID- 11768506 TI - Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent. AB - Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter. PMID- 11768507 TI - An in vitro system for the study of ultrasound contrast agents using a commercial imaging system. AB - An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter. PMID- 11768508 TI - Microencapsulation of carbon particles used as oxygen sensors in EPR oximetry to stabilize their responsiveness to oxygen in vitro and in vivo. AB - The electron paramagnetic resonance (EPR) spectra of some paramagnetic materials exhibit a pO2 (partial pressure of oxygen)-dependent linewidth. By recording the EPR linewidth in vivo using low-frequency EPR spectrometers, it is possible to measure the partial pressure of oxygen in tissues. It has been found, however, that some of the paramagnetic materials with optimal spectroscopic properties in vitro may lose or change their responsiveness to oxygen in tissues. The aim of this study was to microencapsulate paramagnetic particles by biopolymers in order to stabilize their responsiveness to oxygen. Carbohydrate char particles (Bubinga) were encapsulated with different biopolymers: cellulose acetate or cellulose triacetate, silicone and polyurethane. The performance of the materials was evaluated in vitro and in vivo. X-band EPR spectroscopy was used to test the variation of the calibration curve (EPR linewidth as a function of the pO2) after incubation in saline and after prolonged residence in tissues. The stability of the responsiveness to PO2 in vivo was carried out by L-band EPR spectroscopy using mice that received injection of the oxygen sensors in the muscles. After residence in saline and prolonged residence in tissues, only the calibration curve of the silicone-coated (coating weight of 0.5% (w/w)) paramagnetic materials remained unchanged, while those of oxygen sensors coated with cellulose acetate, cellulose triacetate and polyurethane changed. PMID- 11768510 TI - There is no IMRT? PMID- 11768509 TI - Respiratory effects in human functional magnetic resonance imaging due to bulk susceptibility changes. AB - Functional magnetic resonance imaging relies on detecting small changes in the signal in the presence of noise from various sources. It has been shown that periodic variations in the signal at the respiratory frequency occur in the brain and various techniques have been proposed to remove them. However, the precise mechanism by which respiration affects the fMRI signal has not yet been proven. Here, we explore the nature of respiratory signal variations and the artefacts they produce in brain images. Our results demonstrate conclusively that bulk susceptibility variations in the lungs during respiration cause variations in the static magnetic field within the brain tissue. These variations in field strength and homogeneity lead to a shift of the image and a shading of image intensity in the phase encoding direction. These artefacts, if left uncorrected, may lead to the production of spurious activations and/or decreased statistical significance of true activations in fMRI. In addition, these results suggest that respiration effects may not necessarily be well characterized as simple additive noise and that an alternative model based on the physical origins of susceptibility variations may be more appropriate. PMID- 11768511 TI - Optimizing the indexing of a resolution-enhancing tertiary collimator for radiotherapy. AB - A method for improving the resolution of multileaf collimator (MLC) defined radiotherapy fields using a tertiary, slotted grid collimator has been investigated and developed further. The original concept was for each slot to be aligned with each leaf pair of opposing MLC leaves. The total treated area is composed of a series of sub-fields, a pattern of irradiated strips, with the width of each strip defined by the width of the slot and the length by the relative separation of the MLC leaf pair. To complete the field, the patient must be indexed relative to the collimator, with the number of sub-fields required determined by the width of the slots and the spacing between them. Two methods were considered by which this indexing could be achieved: movement of the patient while holding the tertiary collimator fixed, or rotating the grid with the point of rotation defined as the radiation source. Consideration of the movement resolution and precision required for the patient support system for non-cardinal gantry, collimator and table angles cast doubt on the practicality of the use of such a strategy. To assess the effect of divergence on the abutting sub-fields, measurements were also performed to assess the uniformity of single fields generated by the tertiary collimator in planes above and below the isocentre using both methods of indexing. As expected, rotation of the collimator resulted in a similar degree of non-uniformity for any plane chosen, whereas significant dose heterogeneities were introduced to treatment planes within 5 cm above and below the isocentre if the patient support system was used. Therefore, the rotation strategy will be implemented with all future versions of the device. PMID- 11768512 TI - Automated CT marker segmentation for image registration in radionuclide therapy. AB - In this paper a novel, automated CT marker segmentation technique for image registration is described. The technique, which is based on analysing each CT slice contour individually, treats the cross sections of the external markers as protrusions of the slice contour. Knowledge-based criteria, using the shape and dimensions of the markers, are defined to enable marker identification and segmentation. Following segmentation, the three-dimensional (3D) markers' centroids are localized using an intensity-weighted algorithm. Finally, image registration is performed using a least-squares fit algorithm. The technique was applied to both simulated and patient studies. The patients were undergoing 131I mIBG radionuclide therapy with each study comprising several 99mTc single photon emission computed tomography (SPECT) scans and one CT marker scan. The mean residual 3D registration errors (+/- 1 SD) computed for the simulated and patient studies were 1.8 +/- 0.3 mm and 4.3 +/- 0.5 mm respectively. PMID- 11768513 TI - Dosimetric characteristics of dynamic wedged fields: a Monte Carlo study. AB - We have developed a Monte Carlo (MC) technique using the EGS4/BEAM system to calculate dosimetric characteristics of dynamic wedges (DW) for photon beam radiotherapy. The simulation of DW was accomplished by weighting the history numbers of the electrons, which are incident on the target in accordance with the segmented treatment table. Calculations were performed for DW with wedge angles ranging from 15 degrees to 60 degrees as well as for open fields with different field sizes for both degrees 6 and 18 MV beams. The MC-calculated percentage depth dose (PDD) and beam profiles agreed with the measurements within +/- 2% (of the dose maximum along the beam axis) or +/- 2 mm in high dose gradient region. The DW slightly affects energy spectra of photons and contaminating electrons. These slight changes have no significant effects on PDD as compared to the open field. The MC-calculated dynamic wedge factors agree with the measurements within +/- 2%. The MC method enables us to provide more detailed beam characteristics for DW fields than a measurement method. This beam characteristic includes photon energy spectra, mean energy, spectra of contaminating electrons and effects of moving jaw on off-axis beam quality. These data are potentially important for treatment planning involving dynamic wedges. PMID- 11768514 TI - Review of ocular ultrasonography. AB - In this paper, the basics, screening technique and major indications of ocular ultrasound are described. This diagnostic technique proved to be an essential tool to examine intraocular structures when opacified ocular media inhibit direct examination and to evaluate retrobulbar structures when exophthalmos is evident. PMID- 11768515 TI - Radiographic findings during recovery from discospondylitis. AB - The diagnosis of discospondylitis is based on radiographic changes in the vertebrae. The limitations of this method are the time gap between the onset of clinical signs and the first appearance of the radiographic findings, as well as the disassociation between the clinical and radiographic signs during recovery. It is known that the radiographic changes appear only two to four weeks after the onset of clinical signs, but the characteristics of radiographic changes during recovery has yet to be documented, thus making follow-up radiographs difficult to interpret. A prospective and retrospective study was designed to document typical radiographic changes during recovery from discospondylitis. We reviewed 12 dogs that had complete and uneventful recovery with antibiotic therapy alone. Periodic follow-up radiographs and clinical examinations were conducted up to five months after the onset of clinical signs to correlate between the clinical status and radiographic changes during recovery. Although the clinical signs improved within the first 10 days of antibiotic therapy, the radiographic deterioration continued before regression and signs of radiographic recovery were noticed. This radiographic deterioration, despite successful antibiotic therapy, appeared shorter in young dogs (less than one year old) and lasted three to nine weeks in older dogs. PMID- 11768516 TI - MR imaging findings in a dog with intravascular lymphoma in the brain. AB - Intravascular lymphoma (malignant angioendotheliomatosis, angiotrophic lymphoma) is a rare neoplastic disorder in dogs. The literature contains few reports in dogs and a single report in a cat. Intravascular lymphoma is characterized by an intravascular proliferation of malignant lymphocytes. This unique angiocentric distribution of neoplastic cells leads to the characteristic clinicopathologic feature of thromboses and infarctions. In people, intravascular lymphoma has a predilection for vessels in the central nervous system (CNS) and skin. Typically, affected patients have episodic symptoms that coincide with the timing of infarctions. This report details the clinicopathologic description and magnetic resonance (MR) images of a dog with intravascular lymphoma that resulted in multiple CNS infarctions. Abnormalities identified with MR imaging consisted of multifocal hyperintensities observed in pre-contrast T1-weighted, T2-weighted, intermediate-weighted, and FLAIR pulse sequences. Lesions were most conspicuous on the FLAIR images. In addition, there was mild enhancement of the lesions seen in post-contrast T1 weighted images. PMID- 11768517 TI - Chronic subdural hematomas and hydrocephalus in a dog. PMID- 11768518 TI - Gastrointestinal studies in the green iguana: technique and reference values. AB - Five healthy green iguana (Iguana iguana) were used to determine appropriate technique and normal transit times for gastrointestinal contrast studies and to describe normal radiographic anatomy. The animals were maintained at 27-29 degrees C. There was rapid transit through a U shaped stomach, with a median gastric emptying time of 8 h, and median small intestinal transit and small intestine emptying times of 4 h and 16 h respectively. Median large colon transit and emptying times were 15 h and 66 h. Maintaining the iguana at a reduced ambient temperature increased all of these times. The vaso-vagal response or mechanical methods were adequate for restraint. A 25 ml/kg dose of a 25% w/v suspension of barium administered by stomach tube gave the best results. Lateral and ventrodorsal projections of the abdomen should be made immediately following the administration of the barium and at 1-hour intervals for the first 6 h and at 12-hour intervals thereafter until barium can be identified in the distal descending small colon. PMID- 11768519 TI - Radiographic diagnosis-polyostotic lymphoma in a 5 month old dog. PMID- 11768520 TI - Magnetic resonance imaging of cerebral cortical necrosis (polioencephalomalacia) in a dog. AB - A 3-year-old neutered female mixed breed dog was examined because of severe, generalized seizure activity, tetraparesis, and encephalopathic signs. Cerebrospinal fluid (CSF) evaluation was unremarkable except for a mild increase in protein. Serum and CSF titers for infectious diseases were negative. Magnetic resonance (MR) imaging examination of the brain was performed and lesions were found within the cerebral gray matter of the temporal and parietal lobes. The lesions had increased signal intensity on T1, T2, and proton density-weighted images. There was mild inhomogeneous enhancement following intravenous contrast medium administration. Neurologic status improved and the seizures were well controlled, but the dog never regained normal mentation and euthanasia was performed 10 weeks after initial evaluation. At necropsy, severe cerebral cortical necrosis was found in the regions corresponding to the lesions seen on MR imaging examination. Large numbers of fat-containing macrophages (gitter cells) were found within these areas, and are thought to be responsible for the characteristic hyperintensity seen on the MR images. PMID- 11768521 TI - Feline myelography. PMID- 11768522 TI - Ultrasonography of the podotrochlear apparatus in the horse using a transcuneal approach: technique and reference images. AB - The purpose of this paper is to describe the technique for ultrasonographic examination of the podotrochlear apparatus in the horse using a transcuneal approach. In this study, ultrasound scans were performed in 3 normal cadaver limbs and 5 sound horses and images were compared to anatomic sections to establish the normal ultrasonographic anatomy of the podotrochlear apparatus. Detailed description of transverse and sagittal reference ultrasonographic images of this region is provided. This new imaging technique allows the assessment of the distal sesamoid bone flexor surface, the distal portion of the deep digital flexor tendon, the impar distal sesamoidean ligament, and the entheses of the distal phalanx. PMID- 11768523 TI - Ultrasound corner: range ambiguity artifact. PMID- 11768524 TI - Transcutaneous ultrasonography of the coelomic viscera of the ostrich (Struthio camelus). AB - Ultrasonographic examinations were performed on clinically healthy growing and adult nonbreeding female ostriches. Multiple acoustic windows and the normal ultrasonographic appearance of the coelomic viscera were described. Good images of the heart and its major vessels, proventriculus, ventriculus, intestines, liver, and kidneys could be obtained. Additionally, an anechoic structure, believed to function as an urinary bladder, could be imaged in the cloacal region. The pancreas, spleen, thyroid glands, ovary, and adrenals could not be seen in this study. General limitations were the size of the ostriches, massive leg and dorsal muscles, large sternum, the extensive air sac system, compact convoluted intestines, and varying amounts of gastrointestinal gas. Ostriches do not posses a gall bladder, and thus it could not be used as a landmark or acoustic window. The extensive air sac system and feathers did not limit the use of ultrasonography as much as anticipated. Imaging of air sacs should, however, be considered to detect pathology such as air sacculitis, which may result in consolidation. Veterinary PMID- 11768525 TI - Quantitative and qualitative scintigraphic measurement of renal function in dogs exposed to toxic doses of Gentamicin. AB - Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure. PMID- 11768526 TI - Regional brain perfusion in 10 normal dogs measured using Technetium-99m ethyl cysteinate dimer spect. AB - Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern. PMID- 11768527 TI - Proton irradiation of feline nasal planum squamous cell carcinomas using an accelerated protocol. AB - Fifteen cats were treated for squamous cell carcinoma of the nasal planum using proton beam radiation. The protocol used was accelerated with eight equal fractions given on four consecutive days, with a minimum of six hours between fractions. Total dose of radiation delivered was escalated with nine cats receiving 40.4 CGE (60Co Gy equivalent), and three cats each receiving 42.4 and 44.8 CGE. Complete response to the protocol was 60% (9/15), partial response was 33% (5 of 15), and no response was seen in 6.6% (1 of 15). Tumor control rate at one year was 64% and no cat had tumor recurrence after one year. Median survival was 946 days (+/- 516 days). Side effects were minimal with no severe reactions noted in the early or late period. This protocol offers an effective treatment for squamous cell carcinoma of the feline nasal planum with minimal side effects and may be adaptable to conventional radiation sources particularly when the field size is very small. PMID- 11768528 TI - Images from the 2001 ACVR Certifying Examination: CT/MR elective section. PMID- 11768529 TI - Regulatory roles of the GacS/GacA two-component system in plant-associated and other gram-negative bacteria. AB - The sensor kinase GacS and the response regulator GacA are members of a two component system that is present in a wide variety of gram-negative bacteria and has been studied mainly in enteric bacteria and fluorescent pseudomonads. The GacS/GacA system controls the production of secondary metabolites and extracellular enzymes involved in pathogenicity to plants and animals, biocontrol of soilborne plant diseases, ecological fitness, or tolerance to stress. A current model proposes that GacS senses a still-unknown signal and activates, via a phosphorelay mechanism, the GacA transcription regulator, which in turn triggers the expression of target genes. The GacS protein belongs to the unorthodox sensor kinases, characterized by an autophosphorylation, a receiver, and an output domain. The periplasmic loop domain of GacS is poorly conserved in diverse bacteria. Thus, a common signal interacting with this domain would be unexpected. Based on a comparison with the transcriptional regulator NarL, a secondary structure can be predicted for the GacA sensor kinases. Certain genes whose expression is regulated by the GacS/GacA system are regulated in parallel by the small RNA binding protein RsmA (CsrA) at a posttranscriptional level. It is suggested that the GacS/GacA system operates a switch between primary and secondary metabolism, with a major involvement of posttranscriptional control mechanisms. PMID- 11768530 TI - Guidelines for genetic nomenclature and community governance for the model legume Medicago truncatula. AB - At the 2nd Medicago meeting (a satellite of the 1999 IS-MPMI meeting in Amsterdam), investigators perceived a need for standardization of genetic nomenclature in Medicago truncatula, due to the rapid growth of research on this species in the past few years. Establishment of such standards grew out of discussions begun at this meeting and continued electronically throughout the M. truncatula community. The proposed standards presented here are the consensus results of those discussions. In addition to standards for gene nomenclature, a method for community governance and a website for cataloging gene names and submitting new ones are presented. The purpose of implementing these guidelines is to help maintain consistency in the literature, to avoid redundancy, to contribute to the accuracy of databases, and, in general, to aid the international collaborations that have made M. truncatula a model system for legume biology. PMID- 11768532 TI - Rds and Rih mediate hypersensitive cell death independent of gene-for-gene resistance to the oat crown rust pathogen Puccinia coronata f. sp. avenae. AB - The Pca crown rust resistance cluster in the diploid Avena genus confers gene-for gene specificity to numerous isolates of Puccinia coronata f. sp. avenae. Recombination breakpoint analysis indicates that specificities conferred by the Pca cluster are controlled by at least five distinct genes, designated Pc81, Pc82, Pc83, Pc84, and Pc85. Avena plants with the appropriate genotype frequently respond to P. coronata by undergoing hypersensitive cell death at the sites of fungal infection. Autofluorescence of host cells in response to P. coronata occurs in plants that develop visible necrotic lesions but not in plants that lack this phenotype. Two newly described, non-Pc loci were shown to control hypersensitive cell death. Rds (resistance-dependent suppressor of cell death) suppresses the hypersensitive response (HR), but not the resistance, mediated by the Pc82 resistance gene. In contrast, Rih (resistance-independent hypersensitive cell death) confers HR in both resistant and susceptible plants. Linkage analysis indicates that Rds is unlinked to the Pca cluster, whereas Rih is tightly linked to it. These results indicate that multiple synchronous pathways affect the development of hypersensitive cell death and that HR is not essential for resistance to crown rust. Further characterization of these genes will clarify the relationship between plant disease resistance and localized hypersensitive cell death. PMID- 11768531 TI - Complementation of the Magnaporthe grisea deltacpkA mutation by the Blumeria graminis PKA-c gene: functional genetic analysis of an obligate plant pathogen. AB - Obligate plant-pathogenic fungi have proved extremely difficult to characterize with molecular genetics because they cannot be cultured away from host plants and only can be manipulated experimentally in limited circumstances. Previously, in order to characterize signal transduction processes during infection-related development of the powdery mildew fungus Blumeria graminis (syn. Erysiphe graminis) f. sp. hordei, we described a gene similar to the catalytic subunit of cyclic AMP-dependent protein kinase A (here renamed Bka1). Functional characterization of this gene has been achieved by expression in a deltacpkA mutant of the nonobligate pathogen Magnaporthe grisea. This nonpathogenic M. grisea deltacpkA mutant displays delayed and incomplete appressorium development, suggesting a role for PKA-c in the signal transduction processes that control the maturation of infection cells. Transformation of the deltacpkA mutant with the mildew Bka1 open reading frame, controlled by the M. grisea MPG1 promoter, restored pathogenicity and appressorium maturation kinetics. The results provide, to our knowledge, the first functional genetic analysis of pathogenicity in an obligate pathogen and highlight the remarkable conservation of signaling components regulating infection-related development in pathogenic fungi. PMID- 11768533 TI - Yellow lupine cyclophilin transcripts are highly accumulated in the nodule meristem zone. AB - Cyclophilin (CyP) is one of the enzymes that act as peptidylprolyl cis-trans isomerases (EC 5.2.1.8). The cDNA and an intronless gene coding for cytosolic CyP have been isolated from yellow lupine. The deduced amino acid sequence of the characterized open reading frame shows approximately 80% homology with cytosolic CyP from other organisms. Southern blots of genomic DNA indicate that there is a small family of genes for CyP-related genes in the yellow lupine genome. RNA blot analyses demonstrate that CyP genes are expressed in all plant organs. The amount of CyP transcripts is dramatically increased in root nodules. In situ hybridization experiments indicate that CyP transcripts are localized mainly in meristematic tissues, with the highest level observed in the nodule meristem zone. The promoter of the sequenced gene contains 5' AAAGAT 3' and AT-rich motifs that are characteristic for some nodulin promoters. PMID- 11768534 TI - The rkp-3 gene region of Sinorhizobium meliloti Rm41 contains strain-specific genes that determine K antigen structure. AB - The rkp-3 region is indispensable for capsular polysaccharide (K antigen) synthesis in Sinorhizobium meliloti Rm41. Strain Rm41 produces a K antigen of strain-specific structure, designated as the KR5 antigen. The data in this report show that the rkp-3 gene region comprises 10 open reading frames involved in bacterial polysaccharide synthesis and export. The predicted amino acid sequences for the rkpL-Q gene products are homologous to enzymes involved in the production of specific sugar moieties, while the putative products of the rkpRST genes show a high degree of similarity to proteins required for transporting polysaccharides to the cell surface. Southern analysis experiments using gene-specific probes suggest that genes involved in the synthesis of the precursor sugars are unique in strain Rm41, whereas sequences coding for export proteins are widely distributed among Sinorhizobium species. Mutations in the rkpL-Q genes result in a modified K antigen pattern and impaired symbiotic capabilities. On this basis, we suggest that these genes are required for the production of the KR5 antigen that is necessary for S. meliloti Rm41 exoB (AK631)-alfalfa (Medicago sativa) symbiosis. PMID- 11768535 TI - Bradyrhizobium japonicum mutants with enhanced sensitivity to genistein resulting in altered nod gene regulation. AB - Bradyrhizobium japonicum mutants with altered nod gene induction characteristics were isolated by screening mutants for genistein-independent nod gene expression. Plasmid pZB32, carrying a nodY::lacZ transcriptional gene fusion, was introduced into B. japonicum cells that had been subjected to UV mutagenesis. Ten independent transformants producing a blue color on plates containing 5bromo 4chloro-3indolyl-beta-D-galactopyranoside but lacking genistein, indicative of constitutive expression of the nodY::lacZ reporter gene, were isolated. Beta galactosidase activity assays revealed that while all of the 10 strains were sensitive to low concentrations of genistein, none exhibited truly constitutive nodY::lacZ expression in liquid culture. Soybean plants inoculated with three of the mutants were chlorotic and stunted, with shoot dry weights close to those of the uninoculated plants, indicating the absence of nitrogen fixation. Differences in the kinetics of nodY::lacZ expression and lipochitin oligosaccharide Nod signal production suggested that the strains carried different mutations. Some of these strains may be useful in mitigating the low root zone temperature associated delay in soybean nodulation at the northern extent of soybean cultivation. PMID- 11768536 TI - Vascular defense responses in rice: peroxidase accumulation in xylem parenchyma cells and xylem wall thickening. AB - The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae is a vascular pathogen that elicits a defensive response through interaction with metabolically active rice cells. In leaves of 12-day-old rice seedlings, the exposed pit membrane separating the xylem lumen from the associated parenchyma cells allows contact with bacterial cells. During resistant responses, the xylem secondary walls thicken within 48 h and the pit diameter decreases, effectively reducing the area of pit membrane exposed for access by bacteria. In susceptible interactions and mock-inoculated controls, the xylem walls do not thicken within 48 h. Xylem secondary wall thickening is developmental and, in untreated 65-day old rice plants, the size of the pit also is reduced. Activity and accumulation of a secreted cationic peroxidase, PO-C1, were previously shown to increase in xylem vessel walls and lumen. Peptide-specific antibodies and immunogold-labeling were used to demonstrate that PO-C1 is produced in the xylem parenchyma and secreted to the xylem lumen and walls. The timing of the accumulation is consistent with vessel secondary wall thickening. The PO-C1 gene is distinct but shares a high level of similarity with previously cloned pathogen-induced peroxidases in rice. PO-C1 gene expression was induced as early as 12 h during resistant interactions and peaked between 18 and 24 h after inoculation. Expression during susceptible interactions was lower than that observed in resistant interactions and was undetectable after infiltration with water, after mechanical wounding, or in mature leaves. These data are consistent with a role for vessel secondary wall thickening and peroxidase PO-C1 accumulation in the defense response in rice to X. oryzae pv. oryzae. PMID- 11768537 TI - A major quantitative trait locus for resistance to Potato leafroll virus is located in a resistance hotspot on potato chromosome XI and is tightly linked to N-gene-like markers. AB - Potato leafroll virus (PLRV) causes one of the most widespread and important virus diseases in potato. Resistance to PLRV is controlled by genetic factors that limit plant infection by viruliferous aphids or virus multiplication and accumulation. Quantitative trait locus (QTL) analysis of resistance to virus accumulation revealed one major and two minor QTL. The major QTL, PLRV.1, mapped to potato chromosome XI in a resistance hotspot containing several genes for qualitative and quantitative resistance to viruses and other potato pathogens. This QTL explained between 50 and 60% of the phenotypic variance. The two minor QTL mapped to chromosomes V and VI. Genes with sequence similarity to the tobacco N gene for resistance to Tobacco mosaic virus were tightly linked to PLRV.1. The cDNA sequence of an N-like gene was used to develop the sequence characterized amplified region (SCAR) marker N127(1164) that can assist in the selection of potatoes with resistance to PLRV. PMID- 11768538 TI - A physical map of the syringomycin and syringopeptin gene clusters localized to an approximately 145-kb DNA region of Pseudomonas syringae pv. syringae strain B301D. AB - Genetic and phenotypic mapping of an approximately 145-kb DraI fragment of Pseudomonas syringae pv. syringae strain B301D determined that the syringomycin (syr) and syringopeptin (syp) gene clusters are localized to this fragment. The syr and syp gene clusters encompass approximately 55 kb and approximately 80 kb, respectively. Both phytotoxins are synthesized by a thiotemplate mechanism of biosynthesis, requiring large multienzymatic proteins called peptide synthetases. Genes encoding peptide synthetases were identified within the syr and syp gene clusters, accounting for 90% of the DraI fragment. In addition, genes encoding regulatory and secretion proteins were localized to the DraI fragment. In particular, the salA gene, encoding a regulatory element responsible for syringomycin production and lesion formation in P. syringae pv. syringae strain B728a, was localized to the syr gene cluster. A putative ATP-binding cassette (ABC) transporter homolog was determined to be physically located in the syp gene cluster, but phenotypically affects production of both phytotoxins. Preliminary size estimates of the syr and syp gene clusters indicate that they represent two of the largest nonribosomal peptide synthetase gene clusters. Together, the syr and syp gene clusters encompass approximately 135 kb of DNA and may represent a genomic island in P. syringae pv. syringae that contributes to virulence in plant hosts. PMID- 11768539 TI - Mutational analysis of beta-glucanase genes from the plant-pathogenic fungus Cochliobolus carbonum. AB - Two new beta-glucanase-encoding genes, EXG2 and MLG2, were isolated from the plant-pathogenic fungus Cochliobolus carbonum using polymerase chain reaction based on amino acid sequences from the purified proteins. EXG2 encodes a 46.6-kDa exo-beta1,3-glucanase and is located on the same 3.5-Mb chromosome that contains the genes of HC-toxin biosynthesis. MLG2 encodes a 26.8-kDa mixed-linked (beta1,3 beta1,4) glucanase with low activity against beta1,4-glucan and no activity against beta1,3-glucan. Specific mutants of EXG2 and MLG2 were constructed by targeted gene replacement. Strains with multiple mutations (genotypes exg1/mlg1, exg2/mlg1, mlg1/mlg2, and exg1/exg2/mlg1/mlg2) were also constructed by sequential disruption and by crossing. Total mixed-linked glucanase activity in culture filtrates of mlg1/mlg2 and exg1/exg2/mlg1/mlg2 mutants was reduced by approximately 73%. Total beta1,3-glucanase activity was reduced by 10, 54, and 96% in exg2, mlg1, and exg1/exg2/mlg1/mlg2 mutants, respectively. The quadruple mutant showed only a modest decrease in growth on beta1,3-glucan or mixed-linked glucan. None of the mutants showed any decrease in virulence. PMID- 11768540 TI - Chromosomal deletion in isolates of Phytophthora infestans correlates with virulence on R3, R10, and R11 potato lines. AB - In Phytophthora infestans, a cluster of three dominant avirulence genes is located on the distal part of linkage group VIII. In a mapping population from a cross between two Dutch field isolates, probe M5.1, derived from an amplified fragment length polymorphism (AFLP) marker linked to the Avr3-Avr10-Avr11 cluster, hybridized only to DNA from the parent and F1 progeny that is avirulent on potato lines carrying the R3, R10, and R11 resistance gene. In the virulent parent and the virulent progeny, no M5.1 homologue was detected, demonstrating a deletion on that part of linkage group VIII. P. infestans is diploid, so the avirulent strains must be hemizygous for the region concerned. A similar situation was found in another mapping population from two Mexican strains. The deletion was also found to occur in many field isolates. In a large set of unique isolates collected in The Netherlands from 1980 to 1991, 37% had no M5.1 homologue and the deletion correlated strongly with gain of virulence on potato lines carrying R3, R10, and R11. Also, in some old isolates that belong to a single clonal lineage (US-1) and are thus highly homogenous, deletions at the M5.1 locus were detected, indicating that this region is unstable. PMID- 11768541 TI - Overexpression of Pti5 in tomato potentiates pathogen-induced defense gene expression and enhances disease resistance to Pseudomonas syringae pv. tomato. AB - The tomato Pti5 gene encodes a pathogen-inducible ethylene response element binding protein-like transcription factor that interacts with the disease resistance gene product Pto. Overexpression of Pti5 or Pti5-VP16, a translational fusion with a constitutive transcriptional activation domain, in tomato enhanced resistance to Pseudomonas syringae pv. tomato. Constitutive expression of Pti5 or Pti5-VP16 did not affect the basal level of pathogenesis-related gene expression, but it accelerated pathogen-induced expression of GluB and Catalase. The results demonstrate a positive role of Pti5 in defense gene regulation and disease resistance and suggest that a pathogen-activated posttranscriptional regulatory step is necessary for the pathogen induction of the defense gene expression. PMID- 11768542 TI - Activity of nitric oxide is dependent on, but is partially required for function of, salicylic acid in the signaling pathway in tobacco systemic acquired resistance. AB - When tobacco plants were treated by injection with nitric oxide (NO)-releasing compounds, the sizes of lesions caused by Tobacco mosaic virus (TMV) on the treated leaves and on upper nontreated leaves were significantly reduced. The reduction in TMV lesion size was caused by NO released from the NO-releasing compounds; the byproduct formed after release of NO from the NO-releasing compound NOC-18, diethylenetriamine, did not itself alter lesion size. Treatment of tobacco plants with inhibitors of nitric oxide synthase or an NO scavenger attenuated but did not abolish the systemic acquired resistance (SAR) induced by salicylic acid (SA). In NahG transgenic tobacco plants, NO had no effect on lesion size following TMV infection. These results are consistent with the hypothesis that NO plays an important role in SAR induction in tobacco and that NO is required for the full function of SA as an SAR inducer. The activity of NO is fully dependent on the function of SA in the SAR signaling pathway in tobacco. PMID- 11768543 TI - ngl9: a third MADS box gene expressed in alfalfa root nodules. AB - Expression of MADS box genes has previously been localized to the infected cells of alfalfa (Medicago sativa) root nodules. These genes represent the first putative transcription factors to be identified in nodules and are hypothesized to be involved in a signal transduction pathway initiated by the intracellular bacterium. The eventual activation of specific target genes defines pertinent characteristics of this nitrogen-fixing differentiated cell. In this study, we identify a third nodule MADS box gene, ngl9, and demonstrate that the DNA-binding activity of its protein product is dependent on the presence of a second MADS box protein, NMH7. Despite previous results to the contrary, both genes are expressed in the early stages of flower development, further strengthening the premise that nodule developmental programming may capitalize upon existing developmental cascades. PMID- 11768544 TI - Introduction to the Special Issue on "Anxiety Sensitivity and Addictive Behaviors". AB - Anxiety sensitivity (AS) is a cognitive, individual difference variable characterized by a fear of arousal-related bodily sensations due to beliefs that such sensations are signs of impending catastrophic physical, psychological, or social outcomes. AS has been linked to increased risk for the development and maintenance of panic attacks and anxiety disorders, and more recently has been related to risk for other psychopathological conditions including those related to substance misuse. This article introduces a special issue of Addictive Behaviors focusing on cutting edge findings on the relations of AS to substance use and abuse. We set the stage for the following series of eight novel empirical papers by providing a review of background on the ways in which AS has been hypothetically linked to increased risk for the development of substance abuse and addiction. We also consider whether AS might be differentially related to risk for abuse of specific classes of drugs with different pharmacological effects (e.g., depressants vs. stimulants). Finally, we consider how AS might be related to substance use disorder maintenance or relapse risk through its putative effects in increasing drug withdrawal severity and in lowering tolerance for withdrawal symptoms. Our overriding goal in writing this Introduction was to provide an organizational template for integrating the featured studies and to recommend promising directions for future work into the association of AS and substance use-related problems. PMID- 11768545 TI - Anxiety sensitivity and drug or alcohol use in individuals with anxiety and substance use disorders. AB - Anxiety sensitivity (AS) has been linked to both pathological anxiety and substance use problems. We evaluated relations between AS and substance use situations among individuals with substance use disorders (SUDs) and concurrent DSM-IV anxiety disorders. We predicted that AS would be most strongly associated with substance use in situations involving negative emotions and interpersonal conflict in substance abusers with anxiety disorders. This group was compared to substance abusers with concurrent mood disorders and substance abusers without other disorders (N=88). AS was positively related to negative emotion situations substance use for substance abusers with anxiety disorders and for substance abusers without other disorders. Contrary to predictions, significant differences between these groups were not found. The relationship between AS and negative emotion situations substance use remained after controlling trait anxiety in a combined group (anxiety disorders and substance abuse only groups). AS did not predict substance use for participants with concurrent mood disorders. Identification of factors that place anxious patients at risk for substance use problems will have implications for treatment and for the prevention of this form of maladaptive coping. PMID- 11768546 TI - The relations of trait anxiety, anxiety sensitivity, and sensation seeking to adolescents' motivations for alcohol, cigarette, and marijuana use. AB - The present study investigated relations of anxiety sensitivity and other theoretically relevant personality factors to Copper's [Psychological Assessment 6 (1994) 117.] four categories of substance use motivations as applied to teens' use of alcohol, cigarettes, and marijuana. A sample of 508 adolescents (238 females, 270 males; mean age = 15.1 years) completed the Trait subscale of the State-Trait Anxiety Inventory for Children, the Childhood Anxiety Sensitivity Index (CASI), and the Intensity and Novelty subscales of the Arnett Inventory of Sensation Seeking. Users of each substance also completed the Drinking Motives Questionnaire-Revised (DMQ-R) and/or author-compiled measures for assessing motives for cigarette smoking and marijuana use, respectively. Multiple regression analyses revealed that, in the case of each drug, the block of personality variables predicted "risky" substance use motives (i.e., coping, enhancement, and/or conformity motives) over-and-above demographics. High intensity seeking and low anxiety sensitivity predicted enhancement motives for alcohol use, high anxiety sensitivity predicted conformity motives for alcohol and marijuana use, and high trait anxiety predicted coping motives for alcohol and cigarette use. Moreover, anxiety sensitivity moderated the relation between trait anxiety and coping motives for alcohol and cigarette use: the trait anxiety coping motives relation was stronger for high, than for low, anxiety sensitive individuals. Implications of the findings for improving substance abuse prevention efforts for youth will be discussed. PMID- 11768547 TI - Anxiety sensitivity and other emotionality traits in predicting headache medication use in patients with recurring headaches: implications for abuse and dependency. AB - The objective of the present investigation was to clarify the role that anxiety sensitivity (AS) and other related constructs play in headache medication use in patients with recurring headaches. A total of 108 patients (88% female) with chronic recurring headaches (mean duration = 205.6 months) provided complete responses to a self-report inventory administered during a treatment visit to an outpatient neurology clinic. The inventory included measures of depression, trait anger, trait anxiety, fear of pain, AS, and the impact of headache on daily living. AS and fear of pain were used in accordance with their multidimensional conceptualizations. Hierarchical multiple regression analyses were conducted to determine the variables that contributed significantly to the prediction of current over-the-counter analgesic and prescription medication use. After controlling for pain severity, the cognitive anxiety dimension of fear of pain was the only significant predictor of over-the-counter analgesic use. For prescription medication use, the fear of physical catastrophe dimension of AS and the physiological anxiety dimension of fear of pain were significant predictors, although the predictive direction of the former was opposite to that found in prior studies. The models, while significant, accounted for relatively small amounts of variance. Implications of these results and issues of medication abuse and dependency are discussed. PMID- 11768548 TI - The roles of alcohol and alcohol expectancy in the dampening of responses to hyperventilation among high anxiety sensitive young adults. AB - Previous research suggests that high anxiety sensitivity (AS) young adults are particularly sensitive to alcohol's dampening effects on their responses to arousal-induction challenge [Alcohol.: Clin. Exp. Res. 24 (2000) 1656.]. This sensitivity to alcohol reward may place high AS individuals at increased risk for alcohol abuse. Over-and-above alcohol's pharmacological effects, tension reduction expectancies might contribute to alcohol's reactivity-dampening effects in high-AS individuals. The present study examined the role of alcohol and alcohol expectancy factors by activating expectancies experimentally. Forty-eight high-AS young adults were randomly assigned to one of three beverage conditions: alcohol (pharmacology plus expectancy), placebo (expectancy only), and control (no pharmacology and no expectancy). Following beverage consumption and absorption, participants underwent a 3-min voluntary hyperventilation challenge. Replicating and extending previous findings, participants in the alcohol condition showed dampened affective and somatic responses to the challenge, and marginally dampened cognitive responses to the challenge, compared to both placebo and control participants. However, placebo participants did not display dampened responses to the challenge relative to control beverage condition participants. Additional analyses suggested that activation of tension-reduction expectancies might have contributed to an "inverse placebo" effect among high-AS participants administered placebo. Implications of the results for future research and for the prevention and treatment of alcohol problems among high-AS individuals are discussed. PMID- 11768549 TI - Anxiety mediates the association between anxiety sensitivity and coping-related drinking motives in alcoholism treatment patients. AB - Anxiety sensitivity (AS), the tendency to interpret feelings of anxiety as dangerous, is a core dispositional trait in a well articulated and extensively studied cognitive model of proneness to anxiety disorder. In recent years, there has been an increasing body of findings that also links AS to the tendency to use alcohol in general and the tendency to use alcohol as a means of coping with negative affect in particular. We expand on this empirical base by proposing and testing a theoretical model in which anxiety symptoms mediate the association between AS and alcohol use. That is, we propose that AS promotes anxiety symptoms, which, in turn, promote alcohol use aimed at coping with anxiety and other negative affect states. Over a 1-year data collection period, we assessed 82 alcohol-dependent individuals shortly after they began an intensive alcoholism treatment program. Self-reported anxiety symptoms associated with distinct anxiety syndromes were obtained with reference to the month period preceding their entry into the treatment program. Other information, including the presence of withdrawal symptoms, was obtained via interview. We found that syndrome related anxiety symptoms and Trait Anxiety, but not State Anxiety or withdrawal symptoms, mediated the significant association between AS and the self-reported tendency to use alcohol as a means of controlling anxiety symptoms. Demonstrating a similar pattern of findings, but much less robustly so, were tests of these mediator models using alcohol use aimed at coping with negative affect (vs. coping with anxiety per se) as an outcome. In discussing these findings, we attempt to further develop a coherent model that incorporates AS, anxiety symptoms, and drinking motives. Our findings suggest that these relationships may differ for negative affect not specifically related to anxiety. We also discuss the possible associations of AS to withdrawal symptoms implied by our findings. PMID- 11768550 TI - Anxiety sensitivity: relationship to negative affect smoking and smoking cessation in smokers with past major depressive disorder. AB - The present study evaluated whether anxiety sensitivity (AS) was related to negative reinforcement smoking motives and increased risk of relapse during the early stages of a quit attempt. Specifically, the role of AS was evaluated in 60 smokers with past major depressive disorder (MDD) during smoking cessation. Consistent with expectations, AS scores, as indexed by the 16-item Anxiety Sensitivity Index (ASI) [Behaviour Research and Therapy 24 (1986) 1], were positively correlated with smoking to reduce negative affect but were not significantly correlated with smoking for other reasons. Higher ASI scores also were associated with increased risk of lapsing during the first 7 days after quit day. Results suggest that smokers with heightened levels of AS may smoke more often to manage negative moods and may be less able to tolerate early withdrawal symptoms, specifically during early stages of a quit attempt. PMID- 11768551 TI - Affective style among smokers: understanding anxiety sensitivity, emotional reactivity, and distress tolerance using biological challenge. AB - The present investigation evaluated affective style in terms of anxiety sensitivity, emotional reactivity, and distress tolerance in heavy smokers. Specifically, heavy smokers (> or = 20 cigarettes per day) were partitioned into those who were able to quit for at least 7 days (n = 10) and those who were able to quit for less than 7 days (n = 12). All participants completed measures of anxiety sensitivity and maximum breath-holding duration and then were exposed to a 20% carbon dioxide-enriched air challenge. Results indicated that heavy smokers who had not been able to remain abstinent from smoking for at least 1 week during a quit attempt demonstrated significantly greater cognitive-affective reactivity to the challenge relative to their counterparts but did not differ at a physiological level of analysis. Contrary to our hypotheses, neither anxiety sensitivity scores nor maximum breath-holding duration significantly differed between the groups. These findings are discussed in relation to better understanding affective style among heavy smokers. PMID- 11768552 TI - Parental problem drinking and anxiety disorder symptoms in adult offspring: examining the mediating role of anxiety sensitivity components. AB - Preliminary studies have implicated childhood exposure to parental problem drinking as a possible factor in the development of anxiety sensitivity (AS). The present retrospective study was designed to examine the role of exposure to distressing parental problem drinking behaviors, over and above the role of parental alcoholism, in the development of various AS components (psychological, physical, and social concerns) in the offspring. We also examined the possible mediating role of AS components in explaining relations between parental drinking problems and anxiety-related symptoms in the adult offspring. A sample of 213 university students provided retrospective reports of both distress related to parental drinking [Children of Alcoholics Screening Test (CAST)] and parental alcoholism [maternal and paternal forms of the Short Michigan Alcoholism Screening Test (SMAST)]. Participants also reported on their own current AS levels [AS Index (ASI)], general anxiety symptoms [State-Trait Anxiety Inventory Trait subscale (STAI-T)], and lifetime history of uncued panic attacks [Panic Attack Questionnaire-Revised (PAQ-R)]. Scores on the CAST predicted AS psychological and physical concerns (but not social concerns) over and above participant gender and parental alcoholism measured by the SMASTs. Moreover, AS psychological concerns proved a consistent modest mediator of the relations between parental problem drinking on the CAST and both general anxiety and uncued panic outcomes in the offspring. Thus, exposure to distressing parental problem drinking behavior may be one factor that contributes to elevated AS psychological concerns in the child, which in turn may contribute to the development of anxiety disorder symptoms in the offspring. PMID- 11768553 TI - Substance use/abuse and anxiety sensitivity: what are the relationships? AB - The eight articles in this special issue on anxiety sensitivity (AS) and substance abuse provide provocative new information on the relationships, or lack of relationships, between AS and several types of substance use and abuse. The eight articles provide data that extend our understanding of the role of AS in substance abuse with younger people, people who use substances other than alcohol, people who have disorders comorbid with substance use disorders, and people who experience chronic headaches. In addition, one of the articles attempts to determine how AS develops in relationship to parental substance abuse. Finally, several of the studies show that the three Anxiety Sensitivity Index (ASI) subscales (physical concerns, social concerns, and psychological concerns) are uniquely associated with different aspects of substance use/abuse. Each of the articles is discussed as to its merits and potential domains that may require additional research. Finally, several general suggestions are provided for new directions that research on the relations of AS and substance use/abuse should take. PMID- 11768554 TI - Mechanism and clinical significance of metronidazole resistance in Helicobacter pylori. AB - Metronidazole was introduced in 1959 for the treatment of Trichomonas vaginalis, but was subsequently shown to be active against anaerobic and some micro aerophilic bacteria as well. In anaerobic microorganisms with their low redox potential, metronidazole is reduced to its active metabolite by a one-electron transfer step. Metronidazole is often used in treatment regimens for Helicobacter pylori, a microaerophilic bacterium, but resistance to this drug is frequently encountered. The metabolism of metronidazole in H. pylori must differ from that in anaerobic bacteria as metabolites formed by a one-electron transfer are readily re-oxidized in the micro-aerophilic environment of H. pylori. This process is called 'futile cycling' and is accompanied by the formation of toxic oxygen radicals that are neutralized by an active scavenger system. Recently, it has been shown that in H. pylori, in contrast to the situation in anaerobes, an oxygen-insensitive nitroreductase. encoded by the rdxA gene, is responsible for the activation of metronidazole. Activation by this enzyme is by a two-electron transfer step, preventing futile cycling' and thereby enabling the activation of metronidazole in a micro-aerophilic environment. Metronidazole resistance has been shown to be associated with null mutations in the rdxA gene in most clinical isolates. However, there may be some 'background metronidazole susceptibility' in metronidazole-resistant strains caused by other (oxygen-sensitive) nitroreductases. Recently, three meta-analyses of the impact of metronidazole resistance on treatment efficacy have all shown a significant reduction in efficacy of metronidazole containing regimens in patients infected with a resistant strain. The impact of resistance proved to be dependent on the other components of the regimen and on treatment duration. PMID- 11768555 TI - Current insights into the pathogenesis of acute and chronic pancreatitis. AB - For a long time the pathogenesis of pancreatitis has remained enigmatic. Recent developments in cellular and molecular biology, however, have provided a tremendous research impetus and some of its mysteries are finally being disclosed. This review discusses the implications of the discovery of the disease gene in hereditary pancreatitis and outlines recent advances in our understanding of the mechanism and site of trypsinogen activation and the role of immunocytes and cytokines in acute pancreatitis. With respect to chronic pancreatitis, this review focuses on its association with mutations in the cystic fibrosis conductance regulator gene and the mechanisms of pancreatic fibrosis. These advances in our knowledge of the pathogenesis of the disease, together with emerging biotechnological techniques, will boost the development of future therapies aimed at strategically targeting key pathophysiological processes involved in acute and chronic pancreatitis. PMID- 11768556 TI - Recent developments in Helicobacter pylori vaccination. AB - This reviews discusses the recent progress in the development of a vaccine against Helicobacter pylori. To date, this gram-negative, spiral-shaped bacterium is one of the most common infections of mankind. Infection usually occurs during childhood, and when left untreated results in lifelong colonization of the stomach. Helicobacter pylori infection is a chronic gastritis that can lead to peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. Antimicrobial therapy is currently the method of choice for curing H. pylori infection, but complex dosing, inconsistent efficiency, development of antibiotic resistance, costs and various side effects compromise widespread use. As a consequence, new strategies for the prevention and eradication of H. pylori infections are being explored. Vaccines are an attractive option, because they are both effective and economic in use. Natural infection with H. pylori usually results in a strong inflammatory Th1-type CD4(+)T-cell response that does not seem to have any protective effects. Successful vaccination studies indicate that a Th2-type response is required for protection, but the exact mechanisms involved in protective immunization are still poorly understood. Although commercial development of products for clinical trial is underway, many important issues, such as lack of a suitable mucosal adjuvant, and prevention of potential side effects, such as postimmunization gastritis, need to be resolved. PMID- 11768557 TI - Manometry of the gastrointestinal tract: toy or tool? AB - In the eyes of scientific researchers, there are various manometric techniques that are useful tools for studying the motility of the gastrointestinal tract. Clinicians, however, regard most of these techniques as toys, either because they do not lead to clinically relevant results, or because they are too cumbersome in clinical practice. Nevertheless, a number of manometric techniques have reached the status of clinically relevant diagnostic procedure in gastroenterology. Among these, oesophageal manometry is the most important. Not only has conventional oesophageal manometry been added to the diagnostic armamentarium of many hospitals, but also prolonged ambulatory recording of oesophageal pressures (usually combined with pH monitoring). Small intestinal manometry has also gained the status of a diagnostic tool, in particular in patients in whom the existence of pseudo-obstruction syndrome is suspected and in patients in whom total colectomy is considered because of intractable constipation. Sphincter of Oddi manometry is another example of a clinically relevant manometric technique to be used in particular in patients with suspected dyskinesia of the sphincter of Oddi. The value of anorectal manometry may have been overestimated in the past. The most important indication is the exclusion of Hirschsprung disease. The contribution of anorectal manometry to the diagnosis of anismus and to the work up of patients with faecal incontinence is limited. PMID- 11768558 TI - The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. AB - The pathogenesis of inflammatory bowel disease (IBD) remains unknown, although in recent years more data have become available. The contribution of genetic and environmental factors is evident, and the luminal bacterial flora plays a major role in the initiation and perpetuation of chronic IBD. Animal models of IBD have shown that colitis does not occur in a germ-free environment. In human IBD, inflammation is present in parts of the gut containing the highest bacterial concentrations. Moreover, the terminal ileum, caecum and rectum are areas of relative stasis, providing prolonged mucosal contact with luminal contents. Enhanced mucosal permeability may play a pivotal role in maintaining a chronic inflammatory state, due to a genetic predisposition or as a result of direct contact with bacteria or their products. A detective epithelial barrier may cause a loss of tolerance to the normal enteric flora. Furthermore, an increased mucosal absorption of viable bacteria and bacterial products is found in IBD. Serum and secreted antibodies are increased and mucosal T-lymphocytes that recognize luminal bacteria are present. However, there is evidence that the immune system reacts over aggressively towards the normal luminal flora rather than the flora being altered in IBD. Several approaches have been used in attempts to discover a specific microbial agent in the cause of IBD. These include demonstration of the presence of organisms or specific antigens in affected tissues, culture of microbes firm the affected tissues, demonstration of serological responses to several agents, and localization and detection of individual pathogen-specific nucleic acid sequences in affected tissue by in situ hybridization and polymerase chain reaction. So far, no specific micro-organism has been directly associated with the pathogenesis of IBD. Analysis of the luminal enteric flora, however, has revealed differences in the composition of this flora compared to healthy controls. In Crohn disease, concentrations of Bacteroides, Eubacteria and Peptostreptococcus are increased, whereas Bifidobacteria numbers are significantly reduced. Furthermore, in ulcerative colitis, concentrations of facultative anaerobic bacteria are increased. The arrival of new molecular techniques qualifying and quantifying the complex intestinal flora has induced a revival of interest in this microflora. Therapeutic approaches geared towards changing the environment at the mucosal border have been attempted by the use of elemental diets, total parenteral nutrition, surgical diversion of the faecal stream and antibiotics. Over the past few years, the use of probiotics in IBD and other intestinal disorders has gained attention. Strengthened by promising experimental data and commercial interests, research in this field is rapidly expanding. Manipulation of the colonic bacteria with antibiotic drugs and probiotic agents may prove to be more effective and better tolerated than immunosuppressants in the future. PMID- 11768559 TI - Relative efficacies of gastric proton-pump inhibitors on a milligram basis: desired and undesired SH reactions. Impact of chirality. AB - Gastric proton-pump inhibitors (PPIs) are prodrugs. Their acid activation at pH 1.0 inside the canaliculus of a parietal cell should be fast relative to their serum elimination rate. Actually, all PPIs display chemical activation half-lives at pH 1.0 of a few minutes at the most, while being eliminated from serum with a half-life of about 1 h. This is the main reason they show similar antisecretory efficacies on a milligram basis. It is in line with about 5% to 15% higher healing rates in GERD, DU and GU when 40 mg is compared to 20 mg of either omeprazole or pantoprazole. The comparably large biological variation between patient samples explains why some studies show statistically significant differences between the two doses, while others do not. However, it would matter to the individual patient if s/he was the one additionally healed by a 40 mg dose within a defined treatment period. Chemical activation of PPI prodrugs is unwanted in weakly acidic tissue compartments such as lysosomes or secretory granules. However, the ratio of the serum elimination half-life (availability at the target) to the chemical activation half-life at a critical pH 5.0 is reversed only with pantoprazole. when compared to pH 1.0 (i.e. the ratio is < 1 at pH 5.0 and > 1.0 at pH 1.0). This is the basis of the high pH selectivity of pantoprazole. In contrast, rabeprazole is activated at pH 5.0 almost as quickly as it is at pH 1.0 and much faster than it is eliminated from serum. This unwanted reactivity of rabeprazole at pH 5.0 does not contribute to the antisecretory action at pH 1.0 and results in poor pH selectivity. Omeprazole and lansoprazole lie in between, as they are activated, at pH 5.0, about as quickly as they are eliminated from serum. The above activation rates refer to room temperature. At 37 degrees C. the activation rates of all PPIs further increase, by about the same factor of between 3 and 4. This renders their differential pH selectivities even more critical for drug safety. Biological consequences have been reported in the literature. It has been claimed that a dose of 40 mg of the S-enantiomer of omeprazole (esomeprazole) results in 10%-15% higher healing rates in GERD patients, compared to 20 mg omeprazole racemate. The same difference is found when the two doses of omeprazole racemate are compared to each other. This is not surprising, as the chiral PPI prodrug is converted by acid into an achiral cyclic sulfenamide which only then reacts with the proton pump. There is therefore no pharmacodynamic argument in favour of any single enantiomer formulation of any PPI. Moreover, potential pharmacokinetic differences between the enantiomers seem to be of little if any importance in the patient. PMID- 11768561 TI - Treatment of inflammatory bowel disease in childhood. AB - Of all patients with Crohn disease and ulcerative colitis, the first presentation of inflammatory bowel disease (IBD) is at a paediatric or adolescent age in 20% to 30%, most children being prepubertal at diagnosis. It is essential to provide an accurate diagnosis in children suspected of IBD, as the initial treatment of Crohn disease and ulcerative colitis in children is not the same as it is in adults. While the role of enteral feeding in the treatment of Crohn disease in adults continues to be controversial, there is firm evidence to support the use of enteral feeding as primary therapy for Crohn disease in children. Nutrition is improved by enteral feeding, and growth and pubertal development are promoted, while the systemic toxicity of corticosteroid therapy is avoided. Supplementary nocturnal enteral nutrition (with daytime intake of normal diet) after primary therapy and remission induction may be associated with the prolongation of remission. Drug treatment in children with IBD is characterized by a lack of evidence from controlled trials. PMID- 11768560 TI - Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi. AB - BACKGROUND: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. METHODS: Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. CONCLUSION: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis. PMID- 11768562 TI - Barrett oesophagus and adenocarcinoma: an overview of epidemiologic, conceptual and clinical issues. AB - A steady increase in the incidence of adenocarcinoma of the oesophagus and oesophagogastric junction has been observed in Western countries. Patients with distinctive-type Barrett oesophagus are predisposed to developing adenocarcinoma of the oesophagus. Distinctive-type Barrett oesophagus is defined by the presence of intestinal-like goblet cells anywhere in the oesophagus. Adenocarcinomas of the oesophagogastric junction may be associated with short segments of intestinal type columnar epithelium in the distal oesophagus. Prognosis after surgical resection for cancer of the oesophagus or oesophagogastric junction is strongly affected by the extent of the disease at the time of diagnosis. The identification of Barrett oesophagus as a premalignant condition, the recognition of a stepwise neoplastic progression, along with the poor survival rates of advanced oesophageal adenocarcinoma have initiated the practice of endoscopic biopsy surveillance for patients with Barrett oesophagus. There is supporting evidence that endoscopic biopsy surveillance of Barrett oesophagus permits detection of malignancy at an early stage with favourable results after oesophageal resection. Endoscopic treatment modalities should at this time not be generally adopted in the management of patients with early invasive adenocarcinoma of the oesophagus or oesophagogastric junction. PMID- 11768563 TI - Clinical definition of hereditary non-polyposis colorectal cancer: a search for the impossible? AB - Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system, are responsible for the disease. Because of the lack of specific phenotypical features, clinical diagnosis in an individual patient is impossible and relies heavily on family history. Genetic diagnosis by mismatch detection is now possible in a substantial proportion of families. Thus there is a great need for reliable but simple criteria that will help clinicians to recognize patients and families who can be referred for genetic diagnostics. In this article the different criteria that have been formulated and published in recent years are reviewed and the results, in terms of the proportions of subjects satisfying the criteria who were found to have a germline mutation, are discussed. In most studies the criteria were evaluated in only a small number of subjects. A population-based study is currently being carried out in the north of The Netherlands that aims to include 400 patients fulfilling one of a few simple criteria. Mutation analysis will be performed in all patients. The results of this study will help in the formulation of accurate and simple criteria for use in clinical practice. PMID- 11768564 TI - The glutathione biotransformation system and colorectal cancer risk in humans. AB - Evidence for a protective role of the glutathione biotransformation system in carcinogenesis is growing. However, most data on this system in relation to colorectal cancer originate from animal studies. Here we review the human data. In humans, a significant association was found between glutathione S-transferase (GST) activity in the mucosa along the gastrointestinal tract and the corresponding tumour incidence. Low activity was correlated with high tumour incidence and vice versa. Also, in normal colonic mucosa, GST activity is lower in patients at risk of colon cancer than in healthy controls and therefore interventions which increase the glutathione detoxification capacity may reduce cancer incidence. Consumption of vegetables and fruit is associated with a lower risk of colorectal cancer. Human intervention studies showed that (components from) vegetables induced colonic glutathione detoxification capacity. Such an effect could contribute to a lower colon cancer risk, but further data are needed. The human GSTs consist of four main classes--alpha (A), mu (M), pi (P) and theta (T)--each of which is divided into one or more isoforms. Functional polymorphisms are known for the GST genes M1, P1 and T1 and they all lead to less active enzymes compared to the wild-type gene products. However, studies that compared these GST polymorphisms in relation to colon cancer risk were not conclusive with respect to an increased or decreased risk of a particular genotype. Diet or medication can also influence the expression levels of specific isoenzymes and the effect of such interventions on cancer risk deserves more attention. PMID- 11768565 TI - Alternative techniques for the treatment of colon carcinoma metastases in the liver: current status in The Netherlands. AB - BACKGROUND: Review of current treatment modalities for liver metastases resulting from colorectal cancer. METHODS: Literature review. RESULTS: An increasing number of techniques are available for the treatment of colorectal liver metastases. When it is not possible to use the current gold standard, radical surgical resection, many patients can be treated with alternative techniques. Chemotherapy in its present form must be considered as purely palliative, perhaps with the exclusion of isolated liver perfusion: however, this therapy should still be considered as experimental. Most other possible treatments focus on local destruction of the metastases. This can be achieved using either immuno-guided techniques (tumor antibodies which carry a local active agent), direct local application of a toxic agent (injection) or thermo therapy, which has been applied in patients on a large scale. Thermo therapy involves either localized heating, by means or laser photocoagulation or radiofrequency or microwave ablation, or localized freezing using cryo probes. CONCLUSIONS: Local destruction of liver metastases, especially by means of thermo therapy, is feasible and safe. Currently, cryotherapy is most frequently used in patients. New treatment modalities, such as radiofrequency ablation, arc very promising but their true clinical value should be determined in a randomized clinical trial. PMID- 11768566 TI - Practical management of hepatocellular carcinoma. AB - Primary hepatocellular carcinoma (HCC) is one of the ten commonest tumours in the world and occurs mainly in patients with cirrhosis. To date, in Western countries, curative treatment options include partial liver resection or liver transplantation in selected patients with small tumours. Unfortunately, most patients are detected with non-resectable or non-transplantable HCC due to disease extension, hepatic dysfunction or comorbid factors. These patients may benefit from local ablative therapy, such as percutaneous ethanol injection or radiofrequency ablation, with curative intent in patients with small tumours. In advanced HCC chemoembolization has a high response rate, but there is no clear evidence of a survival benefit. In this review we discuss practical considerations in the treatment of HCC and propose an algorithm for the selection of different treatment modalities. PMID- 11768567 TI - Non-alcoholic steatohepatitis: clinical significance and pathogenesis. AB - Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but liver cirrhosis. together with all its sequelae, may develop; sometimes liver transplantation is indicated. NASH should probably be regarded as a two-stage acquired metabolic disorder consisting of the development of the insulin resistance syndrome in a patient with pre-existing metabolic abnormalities. The insulin resistance syndrome may well be the most important metabolic abnormality giving rise to hepatic steatosis. The preexisting metabolic abnormalities can be diverse, and may well be multifactorial and/or polymorphogenetic. A steatotic liver may be more susceptible to the deleterious effects of the pre-existing metabolic abnormalities. Pre-existing metabolic abnormalities of particular interest are increased hepatic iron storage and derangements of lipoprotein metabolism. While awaiting the complete resolution of the pathogenesis, current treatment is largely conservative. Every patient should be encouraged to lose weight and to avoid alcohol and other hepatotoxins. In addition, diabetes, lipid abnormalities and increased iron stores should be looked for. PMID- 11768568 TI - Treatment of chronic hepatitis C: lessons from human immunodeficiency virus dynamics. AB - Treatment of chronic hepatitis C is a major problem. A sustained viral response to interferon alpha monotherapy occurs in <20% of patients. Using a combination therapy of interferon alpha and ribavirin. the sustained response rate in naive hepatitis C patients has increased to 31%-47%. The success of therapy for chronic hepatitis C depends on both virus- and host-related factors, such as age, histology, duration of hepatitis C virus (HCV) carriage and biochemical parameters. During the last 5 years, insight into the dynamics of human immunodeficency virus (HIV) has been obtained by analysing the changes in viral load after starting antiviral treatment. By using a mathematical model of HIV kinetics as an example, an exponentially rapid decline in serum HCV RNA level was seen after the first dose of interferon alpha, followed by a slower exponential decline: a so-called biphasic pattern. The estimated virion half-life varies between 2.7 and 16.8 h. The high virion turnover allows the generation of a heterogeneous quasi-species population of HCVs. It is therefore supposed that initial aggressive treatment can be helpful to prevent the development of mutations that make the virus more defensible for the interferon alpha treatment. Various trials are now being conducted based on this principle of high induction antiviral therapy. PMID- 11768569 TI - Partial liver transplantation. AB - Since the introduction of the split-liver transplantation procedure 15 years ago a variety of partial liver transplantations have been developed. The earliest form of split-liver transplantation consisted of reduction of a whole liver graft to just the left lateral segment or the left liver lobe, which was then small enough to transplant to a young child. The rest of the liver was discarded. This method partially solved the great need for liver grafts for children but as the remaining part of the liver was discarded the method was in fact detrimental for adults on the waiting list. Further surgical development resulted in splitting of the liver ex vivo into two transplantable partial grafts: the left part to a child and the right lobe to an adult. This procedure was successfully introduced but the complicated logistics resulted in prolonged cold ischemia times for the grafts. In order to keep the cold ischemia time as short as possible, the in situ split-liver technique was developed, in which the liver was split in the post mortem donor. Refinement of this operation led to results which were superior to those obtained with the ex vivo method; moreover, it opened the door to living donor liver transplantation. The first successful procedure was performed from a mother to a child, who received the mother's left liver segment. The introduction of this technique resulted over the years in a decrease in the pediatric waiting list to almost zero. As the demand for organs increases every year and the number of donors remains constant in Western countries, the right-lobe living-donor liver transplantation for adults has been introduced. Introduction of all forms of partial liver transplantation has relieved the pressure on waiting lists, especially for children but also for adults. There are, however, serious concerns regarding the high morbidity and mortality rates associated with the living-donor donation procedure. PMID- 11768570 TI - Nutrition, diet and oral health. AB - Teeth are valued, not least for their contribution to appearance and social acceptability. The cost of treating oral disease, though, is high--about 2.2 billion pounds in the UK in 1999-2000. Nutrition and diet are major determinants of oral health or disease and the purpose of this lecture was to review their impact on the more important oral diseases: defects in the structure and appearance of teeth, dental caries, dental erosion, periodontal disease, noma, and oral cancer. There is growing realisation of the detrimental impact of dental impairment on food choice, nutrient intake and nutritional status. A common feature of many of these diseases is that the causes are well known. However, they are not yet preventable because their aetiology (and prevention) is intimately involved with lifestyle. Nevertheless, there are some hopeful signs of progress being made in several areas. PMID- 11768571 TI - Venous thromboembolism prophylaxis used by consultant general surgeons in Scotland. AB - BACKGROUND: Venous thromboembolism (VTE) is a common source of morbidity and mortality in general surgical patients. Guidelines have been produced to help guide doctors through the complex issue of VTE prophylaxis. This study intended to examine the use of VTE prophylaxis amongst general surgeons in Scotland, with reference to nationally produced guidelines. METHOD: A postal questionnaire was sent to all consultant general surgeons in Scotland. They were asked to give their opinion on the best means of VTE prophylaxis in six different clinical scenarios. The responses were evaluated with reference to the guidelines from the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A 69% response rate was achieved. There was a wide variance in the suggested prophylaxis in each of the scenarios. With reference to SIGN guidelines, 35% of responses represented undertreatment, 16% overtreatment and 49% appropriate treatment. CONCLUSION: Despite the publication of VTE guidelines, there is still a wide variety of opinions amongst consultant general surgeons with regards to VTE prophylaxis. Many of the responses were not consistent with such guidelines and represent suboptimal prophylaxis for patients. PMID- 11768572 TI - Pouchitis following restorative proctocolectomy for ulcerative colitis: incidence and therapeutic outcome. AB - BACKGROUND: Pouchitis is a significant sequel of restorative proctocolectomy. This study was undertaken to document the incidence of pouchitis at the Edinburgh Royal Infirmary and to assess outcome of treatment with metronidazole. METHODS: Patients who developed pouchitis following restorative proctocolectomy for ulcerative colitis form the basis of this study. Pouchitis was suspected if patients developed diarrhoea with or without blood, mucus or pus. Diagnosis was confirmed with pouch endoscopy and biopsy. RESULTS: From 1990 to 1999 (10 years) 139 patients underwent restorative proctocolectomy and ileo-anal pouch anastomosis (135 J pouches and 4 W pouches). Their median age was 35 years (range 13-74). There were 68 females and 71 males. The indication for operation was failed medical treatment in 104 patients and toxic megacolon in 35. Forty-seven patients (34%) developed pouchitis (21 females and 26 males). Symptoms were diarrhoea (35), diarrhoea, mucus and pus (5) and diarrhoea and blood (7). Symptoms of pouchitis started at an average of 33.51 + 29.2 months (range 2-102, median 18). All patients were treated with metronidazole for a minimum of one month. Thirty-six patients (77%) resolved on metronidazole alone. Nine patients (19%) went on to develop chronicity and were managed by long-term metronidazole (and/or ciprofloxacin). A further 2 patients (4%) had treatment resistant pouchitis and required pouch excision. CONCLUSION: Pouchitis is common following restorative proctocolectomy for ulcerative colitis. Treatment with metronidazole is associated with improvement in the majority of cases. In patients with chronic pouchitis maintenance of remission is possible with antibiotics. A high index of suspicion is advocated in patients who develop severe diarrhoea following this procedure. PMID- 11768573 TI - A simple method of mesorectal transection for carcinoma of upper third of rectum. PMID- 11768574 TI - The other option in research. AB - As surgery advances rapidly, so the need for a more critical evaluation of new developments becomes more urgent. This is most likely to be developed in the research environment. However, a well conducted and published MSc research project will earn more points in the SpR short-listing process than a poorly conducted and unpublishable two year research study that is unable to generate a thesis leading to a higher degree. PMID- 11768575 TI - The management of brain tumours. AB - Current knowledge on the biology and clinical features of brain tumours is reviewed with particular reference to the most commonly occurring tumours - gliomas, meningiomas and metastases. Unfortunately, the enormous increase in understanding of the biology of these tumours over recent years has not, as yet, been paralleled by advances in treatment or improvements in clinical outcome. Developing adjuvant therapies, ranging from novel means of delivery of radiotherapy and new chemotherapy agents to gene therapy and anti-angiogenic agents, are currently being explored and offer some hope for improvement in our ability to treat these tumours over the next few decades. PMID- 11768576 TI - Inguinal hernia repair. AB - Inguinal hernia repair has been evolving for the past 130 years and the pace of evolution accelerated in the last decade with the introduction of the tension free repair, the laparoscopic repair and the growth of the specialist hernia clinic. The evolution continues and this article sets out to describe the author's approach at the time of writing. PMID- 11768577 TI - A comparison between different formats of educational feedback to junior doctors: a prospective pilot intervention study. AB - OBJECTIVES: Audit feedback is conventionally given in the format of an average performance of the department relative to established guidelines. The impersonality of this feedback format may compromise audit outcome. The aim of the study was to compare personal, peer-comparison feedback, an effective method of changing physician practice, to the 'conventional' departmental one. METHODS: Eleven SHOs working at a central London A&E department were audited in terms of the adequacy of their documentation process. The study comprised patients presenting with closed head injury, acute asthma and chest pain of possible cardiac origin. Personal peer-comparison feedback and average departmental feedback was given for the first two groups, respectively. No feedback was given for the chest pain group, acting as a temporal control. The outcome measure was documentation of the minimum variables, as specified by departmental guidelines. RESULTS: The peer-comparison feedback group showed a significant improvement (p value<0.0001) in two out of three target variables audited, in contrast to the departmental feedback group and the control group which did not show a significant improvement in any of the variables. CONCLUSIONS: Personal, confidential peer-comparison feedback was more effective than departmental feedback, in an audit of process of junior doctors. This pilot study should form the basis of a larger study (more SHOs, wider range of conditions) to establish unequivocally the best format for educational feedback. PMID- 11768578 TI - Extraskeletal Ewings sarcoma of the small bowel: case report and literature review. AB - Extraskeletal Ewings sarcoma is a tumour of neuroectodermal origin sharing close similarities with Ewings sarcoma of bone. We report the case of a 21 year old 16 week pregnant woman presenting with vomiting and weight loss and found to have an extraskeletal Ewings sarcoma of the small bowel. In a review of the literature there are no previous reports of extraskeletal Ewings sarcoma occurring in the small bowel. The diagnosis of extraskeletal Ewings sarcoma and the complicated management of a young pregnant woman with a malignant tumour are described. PMID- 11768579 TI - Diabetic amyotrophy masquerading as quadriceps tendon rupture: a word of caution. AB - Diabetic amyotrophy is predominantly a motor condition that involves various elements of the lumbosacral plexus but particularly that related to the femoral nerve. (1,3) It can present acutely as unilateral thigh pain followed by the development of weakness and later wasting in the femoral muscles, usually first seen in the quadriceps. We report on two cases of diabetic amyotrophy from different hospitals that presented with clinical signs and symptoms of quadriceps rupture. These patients underwent surgical exploration but in both the quadriceps tendons were found to be intact. Post-operative neurological consultations established the diagnosis as diabetic amyotrophy, which was confirmed with electrodiagnostic studies. We conclude that any quadriceps rupture in diabetics should be viewed with caution. Electrodiagnostic studies and imaging with ultrasound and magnetic resonance imaging should be carried out before exploratory surgery. PMID- 11768580 TI - Preventing fogging of spectacles whilst wearing a protective face-mask. PMID- 11768581 TI - The clinically variable R40H mutant ornithine carbamoyltransferase shows cytosolic degradation of the precursor protein in CHO cells. AB - Ornithine carbamoyltransferase (OCT) deficiency is now frequently found in adults with hyperammonaemia affected by mutations that cause partial deficiency of this urea cycle enzyme. One of these mutations (R40H) has occurred in several families and has been found also in asymptomatic relatives. To better understand the phenotypic heterogeneity of this recurrent mutation, we investigated the biological properties of the mutant protein. Using 35S labelling, the import and processing of the R40H mutant OCT protein was investigated in intact CHO cells and in isolated rat liver mitochondria and compared to the wild type and R141Q mutant that causes complete enzyme deficiency. The R40H OCT protein seems to be imported and processed by the mitochondria in a manner similar to that of wild type. However, it is consistently degraded to a smaller fragment in the intact cells, unlike the wild type and R141Q mutant. The mature form of the enzyme is not susceptible to degradation. These data, obtained in CHO cells, suggest that deficiency in OCT enzymatic function conferred by the R40H mutation is likely caused by enhanced degradation of the preprotein in the cytosol. We propose therefore that variation in the rate of OCT turnover is responsible for the heterogeneity of the clinical phenotype in these patients. PMID- 11768582 TI - Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria. AB - The major source of protein in the dietary treatment of phenylketonuria(PKU) is a phenylalanine-free amino acid mixture. Traditionally, these medical products have also contained other nutrients and have been in powder form. However, their disagreeable taste and odour, the large volume required to provide sufficient protein and the inconvenience of their preparation and storage have hindered compliance with consumption among adolescents and adults. We studied the acceptability of a new medical product for the treatment of PKU. This product, Phlexy-10 (SHS North America, Gaithersburg, MD, USA), is available in three forms: sachets of premeasured powder to be constituted as a drink, fruit flavoured bars and prefilled capsules. A vitamin-mineral mixture is separately provided. The forms are interchangeable because each component (one sachet, one bar or 20 capsules) provides 10g of amino acids. Since the product is primarily a source of amino acids, protein requirements can be met using a smaller volume than with traditional medical products. Eleven subjects enrolled in a 24-week trial that included clinical and laboratory evaluations. Nine subjects completed the study and 8 remained on the Phlexy-10 after the study. The powder drink was the favourite module used. One-third of the subjects included the bars and another third included the capsules in their regimens. The vitamin-mineral mixture was the least acceptable component. Mean weekly blood phenylalanine decreased by 40% from mean baseline levels. Blood concentrations of vitamins and minerals were normal except for a low zinc concentration in two subjects and a low vitamin B12 concentration in another. The lower caloric content and the separate vitamin-mineral mixture require careful monitoring of these nutrients. Phlexy-10 appears to be an adequate medical product for the treatment of PKU. Its convenience, flexibility of form and improved taste are appealing to many individuals on diet for PKU. PMID- 11768583 TI - IGF-1 and bFGF reduce glutaric acid and 3-hydroxyglutaric acid toxicity in striatal cultures. AB - Glutaric acid (GA) and 3-hydroxyglutaric acid (3GA) are thought to contribute to the degeneration of the caudate and putamen that is seen in some children with glutaric acidaemia type I, a metabolic disorder caused by a glutaryl-CoA dehydrogenase deficiency. This study assessed the neurotoxicity of GA and 3GA (0 50 mmol/L) compared to quinolinic acid (QUIN) in striatal and cortical cultures. All three acids were neurotoxic in a dose-dependent manner; however, GA and 3GA were both more toxic than QUIN. The neurotoxic effects of low concentrations of GA or 3GA were additive to QUIN toxicity. A series of hormones and growth factors were tested for protection against GA and 3GA toxicity. Insulin (5-500 microU /ml), basic fibroblast growth factor (bFGF; 10 ng/ml), insulin-like growth factor (IGF-1; 50 ng/ml), brain-derived neurotrophic factor (BDNF; 10 ng/ml), glial derived neurotrophic factor (GDNF; 10 ng/ml), and two glutamate antagonists were evaluated in brain cultures to which 7 mmol/L GA or 3GA were added. GA and 3GA neurotoxicities were prevented by bFGF. Attenuation of 3GA-induced neurotoxicity was seen with insulin (5 microU/ml) and IGF-1. BDNF and GDNF had no effects on neuronal survival. Glutamate antagonists MK801 (10 micromol/L) and NBQX (10 micromol/L) failed to prevent GA or 3GA neurotoxicity. We conclude that GA and 3GA are neurotoxic in cultures of embryonic rat striatum and cortex. Striatal neurons were rescued from death by bFGF and IGF-1 but not by glutamate antagonist, suggesting that toxicity in this embryonic system is not necessarily mediated by glutamate receptors. PMID- 11768584 TI - Identification of novel CBFA1/RUNX2 mutations causing cleidocranial dysplasia. AB - Core binding factor A1 (CBFA1/RUNX2) is a runt-like transcription factor essential for osteoblast differentiation. Haplotype insufficiency causes cleidocranial dysplasia (CCD), a syndrome featuring supernumerary tooth buds, delayed tooth eruption, patent fontanels, Wormian bones, short stature, dysplasia of the clavicles, growth retardation and hypoplasia of the distal phalanges. We identified novel CBFAI/RUNX2 mutations after PCR and direct sequencing of patient leukocyte DNA. In family 1 mother and son are affected by CCD. Both carry the missense mutation R190W (CGG > TGG). This nucleotide change introduced a BsmI restriction site, which was used to independently confirm the mutation. It was absent in healthy members of the family. Family 2, in which father and daughter are affected by CCD, shows a deletion of nucleotide C821. This deletion causes a frameshift mutation with premature stop after the insertion of 18 aberrant amino acids. Healthy family members did not have this mutation. The clavicular dysplasia was more pronounced with the R19OW mutation, while the bone density was markedly reduced in individuals with either mutation, suggesting a previously underemphasized increased risk for osteoporosis in CCD. PMID- 11768585 TI - Characterization of altered myocardial fatty acid metabolism in patients with inherited cardiomyopathy. AB - Inherited defects in myocardial long-chain fatty acid metabolism are increasingly recognized as a cause of cardiomyopathy and sudden death in children. To evaluate whether the phenotypic expression of these genetic diseases could be delineated using positron emission tomography (PET), 11 patients with inherited defects in fatty acid metabolism were evaluated and results were compared with those of 6 nonaffected siblings. Myocardial perfusion, myocardial oxygen consumption (MVO2), and long-chain fatty acid metabolism were determined noninvasively with PET using quantitative mathematical models. There were no differences in haemodynamics, perfusion, MVO2 or plasma substrate levels between groups. Patients with defects in enzymes of fatty acid beta-oxidation (acyl-CoA dehydrogenase and 3-hydroxyacyl CoA dehydrogenase deficiencies) (n = 5) had diminished myocardial palmitate oxidation compared with healthy siblings (3.2 +/- 3.0 vs. 13.0 +/- 5.6 nmol/g per min, p < 0.03) and a decrease in the percentage of MVO2 accounted for by palmitate (2% +/- 3% vs. 9% +/- 5%, p < 0.04). In these patients, extracted palmitate was shunted into a slow-turnover compartment (predominantly reflecting esterification to triglycerides) with expansion of palmitate in that pool (185 +/ 246 compared with 27 +/- 67 nmol/g in healthy siblings,p < 0.02). In contrast, myocardium of patients with carnitine deficiency (n = 6) (all on oral carnitine therapy) had normal palmitate extraction but expansion of the interstitial/cytosolic fatty acid pool (617 +/- 399 vs. 261 +/- 73 nmol/g in healthy siblings, p < 0.04), suggesting different mechanisms for handling upstream fatty acyl intermediates. Thus, PET can be used to noninvasively assess abnormal myocardial handling of fatty acids in patients with inherited defects of metabolism. This approach should be useful in the assessment of altered myocardial fatty acid metabolism associated with cardiomyopathy as well as for evaluating the efficacy of therapeutic interventions in affected patients. PMID- 11768586 TI - A fluorimetric enzyme assay for the diagnosis of MPS II (Hunter disease). AB - 4-Methylumbelliferyl-alpha-iduronate 2-sulphate was synthesized and shown to be a specific substrate for the lysosomal iduronate-2-sulphate sulphatase (IDS). Fibroblasts (n = 17), leukocytes (n = 3) and plasmas (n = 9) from different MPS II patients showed < 5% of mean normal IDS activity. The enzymatic liberation of the fluorochrome from 4-methylumbelliferyl-alpha-iduronate 2-sulphate requires the sequential action of IDS and alpha-iduronidase. A normal level of alpha iduronidase activity was insufficient to complete the hydrolysis of the reaction intermediate 4-methylumbelliferyl-alpha-iduronide formed by IDS. A second incubation step in the presence of excess purified alpha-iduronidase is needed to avoid underestimation of the IDS activity. PMID- 11768587 TI - Effect of ramipril in a patient with glycogen storage disease type I and nephrotic-range proteinuria. AB - We studied the effect of ramipril on urinary protein excretion and arterial pressure in a 27-year-old patient with GSD Ia and heavy proteinuria (2-3 g /24 h). Ramipril therapy resulted in an important reduction of proteinuria (0.3-0.5 g/24 h): no changes were observed in arterial pressure and renal function during the 12-month follow-up. We conclude that treatment with ramipril can be employed effectively and safely in GSD Ia patients with nephrotic-range proteinuria. PMID- 11768588 TI - Thiamin-responsive maple syrup urine disease: seizures after 7 years of satisfactory metabolic control. PMID- 11768589 TI - Mitochondrial myopathy, cardiomyopathy and psychiatric illness in a Spanish family harbouring the mtDNA 3303C > T mutation. PMID- 11768590 TI - Standardisation for in vitro toxicity tests. PMID- 11768591 TI - Application of cell cultures to toxicology. PMID- 11768592 TI - Immortalisation of primary cells. AB - Knowledge of the target cells is fundamental to maximise efficiency in attempts at immortalisation of specific cell types. It is also important to optimise the primary cell culture system to promote the survival of the target cell population. Other important factors that may influence the success in obtaining immortalised cells include the toxicity and efficiency of the immortalisation procedure. These can be assessed experimentally and if necessary appropriate techniques can be employed to purify the target cells. When cell lines have been established it is vital to assess them at an early stage for desired scientific and practical features as well as determining their stability and life-span. Furthermore, early characterisation of cell line authenticity (e.g. genetic characters, species of origin) and quality control testing will avoid wasted time and resources should contamination with micro-organisms or another cell line occur. Establishing a programme of immortalisation is a serious undertaking that should only be considered when there are no candidate continuous cell lines available. However, new approaches to modify the biology of cells to give extended life-span, whilst retaining the characteristics of differentiated cells in vivo, will hopefully provide valuable new substrates for in vitro toxicology. PMID- 11768593 TI - Safety considerations for in vitro toxicology testing. AB - A range of hazards may be encountered in in vitro toxicology laboratory work. Such hazards are primarily chemical reagents for which the level of risk, particularly with long-term exposure, may be difficult to ascertain. Cells and tissues may also present biosafety concerns and it is important that risk assessments are prepared for each procedure before commencing project work. Ideally control measures should be simple and combine the use of appropriate equipment with documented procedures supported by risk assessments. In any laboratory staff and procedures change significantly over time, thus monitoring of procedures (including waste disposal) and a comprehensive training programme for all staff are essential components to assure both the quality and safety of laboratory work. PMID- 11768594 TI - The drug-metabolizing enzymatic system and the experimental tools used for in vitro toxicology for metabolic studies. PMID- 11768595 TI - Cell culture models for hepatotoxicology. PMID- 11768596 TI - Intestinal cell culture models: applications in toxicology and pharmacology. PMID- 11768597 TI - Cell culture models for neurotoxicology. PMID- 11768598 TI - Recombinant cell lines for stress reporter assays. PMID- 11768599 TI - A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge. AB - BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule. While ductography has been advocated as the main procedure in patients with nipple discharge, fiberoptic ductoscopy (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast through nipple orifice exploration. METHODS: We applied ductography and FDS to 65 women who had nipple discharge, and compared their utility. RESULTS: Intraductal lesions occurred in the segmental duct and the first, second, third, fourth, fifth, and sixth branches in decreasing frequency with ductography and FDS screening. The detection rates of intraductal abnormal lesions by ductography and FDS and the their combination were 89.1 (37 patients), 97.4 (38 patients), and 97.5% (39 patients) respectively. Ductal washings performed during FDS were effective to obtain representative exfoliated ductal cells which could be evaluated (sensitivity 50%, specificity 94.3%, and diagnostic accuracy 89.7%). As a result, we diagnosed 35 cases of benign lesions and four cases of malignant lesions by cytological or/and histological examination. CONCLUSION: Ductography and fiberoptic ductoscopy are useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge. PMID- 11768600 TI - The polymorphic CAG repeat of the androgen receptor gene: a potential role in breast cancer in women over 40. AB - Previous investigations into the relationship of CAG-repeat lengths in the androgen receptor (AR) gene to female breast cancer (BC) have yielded somewhat confusing results. Decreased AR transactivational activity lowers androgen:estrogen balance, and may thereby effect functional hyperestrogenicity. This may promote the pathogenesis of BC. To elucidate whether longer CAG repeats of the AR gene (AR), which correlate with lower transactivational activity of the AR, are associated with BC in women over 40, we examined the distribution of CAG repeat lengths in BC tissue from this population. The BC tissue was histologically graded as: Grade 1, well differentiated (WD); Grade 2, moderately differentiated (MD); and Grade 3, poorly-differentiated (PD). Analysis showed significant differences as compared to controls when CAG lengths greater than 21 were examined, and that alleles with > or = 26 repeats were 2.4-fold more frequent in BC samples than in constitutional samples from a normal population. A significant shift to greater CAG-repeat lengths, appeared in WD and MD tumors only. Our results give some indication as to the progression of BC by suggesting that hypotransactive ARs with long polyglutamine (polyGln) tracts may have a role in the initiation and/or progression of BC. PD tumors tended to have shorter than normal CAG-repeat lengths. In this case it is hypothesized that the ARs have now become hypertransactive, possibly coinciding with the estrogen resistance that is associated with PD tumors. Whether this shift is of germline or somatic origin was not clear, though the appearance in 14% of the BC samples of a third CAG repeat length indicates that it may be somatic. PMID- 11768601 TI - Polymorphic CA repeats in the IGF-I gene and breast cancer. AB - Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16-7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42-18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility. PMID- 11768602 TI - DNA strand breaks and cell cycle perturbation in herceptin treated breast cancer cell lines. AB - BACKGROUND: Herceptin is a humanized antibody that binds to the product of the HER-2 oncogene. Clinical studies have indicated that treatment with Herceptin may slow disease progression in tumors expressing high levels of the HER-2 antigen. However, the mechanism of this action is not known. METHODS: Four different cell lines were used that had different levels of HER-2 expression. Treated and nontreated cells were analyzed for DNA strand breaks and cell cycle perturbation using standard flow cytometry methods. RESULTS: In this study we found that cell lines expressing high levels of HER-2, when treated with Herceptin, exhibited marked increases in DNA strand breaks as measured by the TUNEL assay, and that these cells also exhibited slowed growth. BT-474 and SKBR-3 cell lines, both of which express high levels of the HER-2 antigen, had significant increases in labeled nucleotide expression at 3 and 6 day time points following exposure to Herceptin at a concentration of 10 microg/ml. Similar treatment of MCF-7 and MDA 231 cell lines, both of which express low levels of HER-2, had little effect on the level of labeled nucleotide expression at either the 3 or 6 day time points. Following 4 days of Herceptin treatment, BT-474 and SKBR-3 cell lines had significant decreases in the percentage of cells in the S phase of growth. This effect was not seen in either the MCF-7 or MDA-231 cell lines. CONCLUSION: Herceptin has a biological effect only on cells that contain high levels of HER 2. This effect is a decrease in cell proliferation that is coincident with, and may be caused by an increase frequency of DNA strand breaks. PMID- 11768603 TI - Lunar phases and survival of breast cancer patients--a statistical analysis of 3,757 cases. AB - The potential influence of lunar phases on human life has been widely discussed by the lay press. The purpose of this study was to find out whether the timing of surgery during particular lunar phases influences the survival of breast cancer patients. It has been postulated that breast cancer surgery performed during the waxing moon, or particularly at full moon, is associated with a poorer outcome. We tested this hypothesis by evaluating the overall survival for 3,757 consecutive patients with invasive breast cancer. All patients underwent either modified radical mastectomy or breast conserving surgery plus radiotherapy, followed by adjuvant cytotoxic or hormonal therapy. The date of definitive surgery was allocated to the lunar phases. 1,904 (50.7%) patients were operated on during the waxing moon and 1,853 (47.3%) during the waning moon. The median follow-up was 74 months (range 1-372 months). The mean age at primary surgery did not differ significantly in the two groups 58.39 (SD 13.14) versus 58.34 (12.75) (p >0.05, t-test). Breast cancer stages at initial diagnosis were evenly distributed according to the lunar phases (p = 0.325; chi-square). Survival curves were plotted according to the method of Kaplan-Meier. No significant differences were observed when timing of surgery was allocated to the lunar phases (p = 0.4841, log-rank). Subgroup analysis of premenopausal patients revealed similar results (p = 0.2950, log-rank; n = 1072). Using multivariate Cox modelling, we found a significant association between the patient's age, stage of disease and survival, whereas no association with survival was observed for the timing of surgery (RR= 1.062; 95% CI, 0.970-1.163; p = 0.1937). No significant differences in overall survival of breast cancer patients were observed when timing of breast cancer surgery during the lunar cycle was considered. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any recommendations for scheduling patients for surgery at any particular day of the lunar phase. PMID- 11768604 TI - Survival of women with breast cancer in france: variation with age, stage and treatment. AB - This study examines survival of women with breast cancer using a sample of 1564 cases occurring in 1990 taken from all cases recorded in seven French cancer registries. Age at diagnosis pathological stage (pTNM) and treatment were the criteria selected for the study of the survival. We studied the 5-year observed survival and the relative survival. Tumors pT1 represented 46.7% cases, pT2: 31.6%, pT3 and pT4: 9.2%, and 52% of the tumors had no nodal involvement or metastasis. For cases without surgical treatment the prognosis was poor (observed survival 18.7%, relative survival 25.9%). For women benefiting from neoadjuvant treatment, observed survival rate was 65% after 5 years and relative survival rate 69.1%. For women who were treated first with surgery, the observed survival was 79.5% and the relative survival 86.7%. The survival rate for women under 40 years was slightly lower than for the 40-54-year-old. Using relative survival the youngest group had the worst prognosis and the oldest group the best. In older women, therapeutic strategy might have been more selective which leads to a better prognosis than in the younger age groups treated in a comparable way. PMID- 11768605 TI - Two distinct groups of non-attenders in an organized mammography screening program. AB - OBJECTIVE: To find out reasons for non-attendance and to study subgroup differences of the non-attenders in an organized mammography screening program. DESIGN: Prospective for background and psychosocial factors, retrospective for reasons of non-attendance. SETTING: Finnish screening based on personal first round invitations, with 89% attendance rate. PARTICIPANTS: Four hundred thirty six women with both pre-screening response to socioeconomic and psychosocial measures, and post-screening response reporting reasons of non-attendance. MAIN RESULTS: Most common single reason for non-attendance was previous recent mammogram (53%), but also reasons related to practical obstacles, worry and fear, knowledge and attitudes, and organization of screening were mentioned. Two distinct groups of non-attenders were found based on the reasons for non attendance. Those who did not attend because a mammogram taken elsewhere (ELSE, n = 233) were urban, well-to-do women, who took care of their health by own initiation and felt more susceptible to breast cancer, and also expected mammogram to be painful. Other (real) non-attenders (REAL, n = 155) were less compliant with health recommendations and services, more socially isolated, depressed and anxious than ELSE. Level of depression among REAL was clearly higher (10.80) than the mean value (7.91, SD = 7.28) of the age group, and was also slightly above the cut-off score of 10 indicating mild or moderate depression. Trait anxiety was also markedly higher (40.18) than that of the same age group (37.76, SD = 8.95). CONCLUSIONS: Further research should clarify determinants and consequences of depression and anxiety among real non-attenders. Knowledge gaps and attitudinal barriers among non-attenders require more targeted campaigns. PMID- 11768606 TI - The early relapse of premenopausal patients after surgery for node-positive breast carcinoma. PMID- 11768607 TI - Micro-metastases in axillary lymph nodes: an increasing classification and treatment dilemma in breast cancer due to the introduction of the sentinel lymph node procedure. AB - BACKGROUND: Sentinel lymph node (SN) biopsy will increasingly replace axillary lymph node dissection (ALND) for staging in breast cancer. For daily practice, examination of the SN by serial sectioning (SS) and/or immunohistochemistry (IHC) is being promoted. Use of these techniques may result into stage migration due to the increased detection of micro-metastases. The consequence may be overshooting of patients with adjuvant therapy, as the prognostic relevance of (small) micro metastases and isolated tumor cells is unclear. METHODS: The prognostic impact of micro-metastases is determined by reviewing ALND studies with a follow up of at least 5 years, including more than 100 patients, before the SN era. Furthermore, studies in which conventionally haematoxylin-eosin (H&E) negative SNs are investigated for occult metastases by SS and/or IHC are reviewed. RESULTS: In only one of eight studies, occult metastases were an independent risk factor for reduced survival. The outcome is dependent on the size of the nodal metastasis. IHC and SS as used in the SN procedure indeed induce a shift from pNO to pN1a (according to TNM). CONCLUSION: By the thorough pathologic examination of the SN, isolated tumor cells and micro-metastases are more frequently detected. We propose to classify small micro-metastases (<0.5 mm) in a separate pN1a(min) category (min for minimal) to prevent stage migration. As the prognostic relevance of isolated tumor cells and (small) micrometastases has not been proven, the value of adjuvant therapy can be questioned for patients with otherwise good prognostic factors. PMID- 11768608 TI - Association of steroid receptor coactivator AIB1 with estrogen receptor-alpha in breast cancer cells. AB - The steroid receptor coactivator AIB1 (amplified in breast cancer-1) is a transcriptional coactivator which has been found to be amplified in breast cancer. We have now investigated the role of the AIB1 protein in breast cancer cell lines. Although detectable levels of AIB1 were present in most cell lines, high levels of AIB1 expression were observed only in the ER-positive cell lines MCF-7 and BT-474 by western blot analysis. Newly developed monoclonal antibodies (mAbs) were used in several assays to show an association between AIBI and estrogen receptor-alpha (ER). AIB1 and ER co-localized to the nucleus of ER positive cell lines as shown by immunofluorescence microscopy, and a functional association of native AIB1 and ER in MCF-7 nuclear extracts was shown by EMSA. Recombinant ER also recruited AIB1 protein from nuclear extracts, shown by EMSA and by precipitation of ER-complex proteins bound to a biotinylated-ERE DNA target. Additionally, anti-AIB1 mAbs were able to immunoprecipitate ER from nuclear extracts of chemically cross-linked cells but not from uncross-linked cells. Both immunoprecipitation and oligonucleotide precipitation studies demonstrated the presence of p300 and CBP as part of the ER transcriptional complex. These results suggest that AIB1 and ER do associate physically in ER positive breast cancer cell lines. We propose that in AIB1 amplified breast cancers, a heightened AIB1/ER association may play a crucial role in the progression of these tumors. PMID- 11768609 TI - MRNA expression of genes altered by 5-azacytidine treatment in cancer cell lines is associated with clinicopathological parameters of human cancers. AB - OBJECTIVE: We attempted to identify tumor-related genes whose expression is affected by DNA methylation and that participate in the determination of the biological characteristics of human cancers. METHODS AND MATERIALS: We used the differential display method in ten 5-azacytidine-treated human cancer cell lines. Time-dependent induction of mRNA expression of Wip1, TROP2, B4-2 protein, BRCA-2 region transcription unit CG005, cofilin, ROCK, CD44. and interferon-inducible protein 6-16 was observed during 5-azacytidine treatment. We then evaluated the mRNA expression of these genes in 26 stomach and 32 colorectal cancers and 44 hepatocellular carcinomas (HCCs) and in the corresponding non-cancerous tissues. RESULTS: Significantly reduced mRNA expression of Wip1, B4-2, and cofilin in stomach cancers, of Wip1, B4-2, BRCA-2 region transcription unit CG005, cofilin, and ROCK in colorectal cancers, and of TROP2, B4-2, and BRCA-2 region transcription unit CG005 in HCCs, was observed in comparison with the corresponding non-cancerous tissues, whereas overexpression of TROP2 was detected in colorectal cancers. Reduced expression of Wip1 and BRCA-2 region transcription unit CG005 was significantly correlated with poorer differentiation of HCCs, and mRNA expression of these genes was significantly reduced in HCCs associated with portal vein involvement compared with HCCs without such involvement. Expression of TROP2 mRNA was significantly higher in chronically diseased liver from HCC patients compared with histologically normal liver, but was reduced in progressed HCCs. Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients. CONCLUSIONS: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes. PMID- 11768610 TI - Nicotinic receptor-mediated activation by the tobacco-specific nitrosamine NNK of a Raf-1/MAP kinase pathway, resulting in phosphorylation of c-myc in human small cell lung carcinoma cells and pulmonary neuroendocrine cells. AB - OBJECTIVE: Small cell lung carcinoma (SCLC) expresses phenotypic features of pulmonary neuroendocrine cells and demonstrates a strong etiologic association with smoking. SCLC cell lines express a Raf-1-dependent mitogenic signal transduction pathway, which is thought to transduce the mitogenic signals initiated by neuropeptide autocrine growth factors. Recent studies have identified the tobacco-specific carcinogenic nitrosamine 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone (NNK) as a site-selective high-affinity agonist for the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), which regulates the growth of a significant subset of SCLC in vitro by stimulating the release of the autocrine growth factor serotonin. The purpose of this study was to identify signaling events initiated by binding of NNK to the alpha7 nAChR. DESIGN: We have used a human SCLC cell line and fetal hamster pulmonary neuroendocrine cells with in vitro kinase activation assays and western blots to assess the levels of expression and activation of Raf-1, MAPK and c-myc to address this issue. RESULTS: Our data show that NNK activates the Raf-1, MAP kinase pathway, resulting in phosphorylation of c-myc. The activation of this signal transduction pathway by NNK was inhibited by the site-selective antagonist for the alpha7 nAChR alpha-bungarotoxin (alpha-BTX) or by the serotonin reuptake inhibitor imipramine, suggesting that the responses to NNK were mediated by nicotinic receptor-initiated release of serotonin. Accordingly, NNK-induced 5-HT release was blocked by alpha-BTX while NNK-induced DNA synthesis was inhibited by alpha BTX, imipramine, the PKC inhibitor sphingosine or the MEK inhibitor PD98059. SCLC cells demonstrated high basal levels of 5-HT release, DNA synthesis, and over expressed Raf-1 and MAPK protein suggesting the constitutive activation of an upstream regulator such as the alpha7 nAChR. CONCLUSION: Our findings link, for the first time, the stimulation of a nicotinic acetylcholine receptor by a cancer causing agent with the activation of a Raf-1/MAPK/c-myc signaling pathway. Furthermore, our data suggest that serotonin uptake inhibitors may protect against the development or be useful in the clinical management of SCLC. PMID- 11768612 TI - AP-1 and heat shock protein 27 expression in human astrocytomas. AB - PURPOSE: In previous work we have shown that the expression of heat shock protein 27 (Hsp27) is associated with anaplastic potential of astrocytomas (Anticancer Res 1997, 17:2677-2682). Heat shock protein-coding genes have been found to have a putative AP-1 (activator protein-1)-binding site in their promoter region and the synthesis of these proteins is induced by the same extracellular stimuli that also activate AP-1 (a homo/heterodimer of members of the Jun and Fos families). In order to detect the putative relation of Hsp27 with AP-1 activation in human astrocytomas we examined eighty astrocytic tumors with different grades of malignancy for c-Jun, c-Fos, and Hsp27 expression. METHODS: Six pilocytic astrocytomas (WHO grade I), 15 diffuse fibrillary astrocytomas (WHO grade II), 19 anaplastic astrocytomas (WHO grade III), and 40 glioblastomas multiforme (WHO grade IV), were studied by immunohistochemistry using monoclonal and polyclonal antibodies directed against human Hsp27, c-Fos, and active (phosphorylated) forms of c-Jun (p-c-Jun). Monoclonal antibodies against the phosphorylated forms of the over-expressed MAP kinases JNK (c-Jun N-terminal kinase) (p-JNK) and p38 (p-p38) were also used. RESULTS: Overexpression of p-c-Jun, c-Fos and p-JNK was observed in the majority of glioblastomas (grade IV) whereas only minimal expression was noted in diffuse fibrillary astrocytomas (grade II). Hsp27 expression was observed only in the tumor specimens where c-Jun and c-Fos were co-expressed. AP 1/Hsp27 co-expression was associated with ascending grading of malignancy and it was independent of the proliferation index of the tumors. CONCLUSIONS: Our findings suggest that during malignant progression of astrocytomas there is activation of signal transduction cascade(s) culminating in AP-1 induction. PMID- 11768611 TI - Vaccination with IL-18 gene-modified, superantigen-coated tumor cells elicits potent antitumor immune response. AB - OBJECTIVE: To investigate the induction of antitumor immune response by vaccination with interleukin-18 (IL-18) gene-modified, C215Fab-SEA-coated tumor cells. MATERIALS: A B16-C215 cell clone stably expressing C215 antigen was established by transfecting the gene-encoding C215 antigen into B16 melanoma cells. The manipulated tumor cell vaccine was prepared with B16-C215 cells genetically modified with the IL-18 gene, coated with the fusion protein of SEA and the Fab region of C215 mAb (C215Fab-SEA) which specifically binds to the C215 antigen and then irradiated. C57BL/6 mice were vaccinated with IL-18 gene modified, C215Fab-SEA-coated B16-C215 cells followed by tumor challenge. Tumor growth and survival time were observed. The expansion of CD4+, CD8+ cells in lymphocytes derived from draining lymph node was detected by FACS. Induction of CTL activity by vaccination was measured by 51Cr release assay. RESULTS: IL-18 gene-modified, C215Fab-SEA-coated B16-C215 cell vaccine effectively stimulated lymphocyte proliferation and CD4+, CD8+ cell expansion in vitro. It was more immunogenic than B16-C215 cells genetically modified with IL-18 gene alone or B16 C215 cells coated with C215Fab-SEA alone. Immunization of the mice with the manipulated vaccine elicited protective immunity against the following tumor challenge of parental B16-C215 and wild-type B16 cells. Significant expansion of CD4+, CD8+ T cells was observed in the draining lymph node of the immunized mice when compared with that in unvaccinated mice. Higher CTL activity was induced in vaccinated mice than that in unvaccinated mice. CONCLUSION: Vaccination with IL 18 gene-modified, C215Fab-SEA-coated tumor cells elicited potent antitumor response through induction of tumor-specific immune response. PMID- 11768613 TI - Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors. AB - PURPOSE: The constitutive activation of Ras proteins by point mutation is the most frequently observed oncogene activation in human malignancies. The goal of this study was to investigate whether the constitutive activation of RhoA, Rac1, and Cdc42 proteins by point mutations, which can lead to experimental transformation of cultured cells, actually occurred in a panel of invasive colorectal and breast tumors. METHODS: We performed denaturing gradient gel electrophoresis and sequencing of transcripts amplified by reverse transcription and PCR for RhoA; we used direct sequencing of PCR-amplified genomic DNA to search for mutations in coding exons of the Rac1 and Cdc42 genes. RESULTS: Although mutations of the Kras4B and the p53 genes were detected using these methods, no mutation was found in the coding sequences of RhoA, Rac1, and Cdc42 genes, in primary as well as in associated metastasis. CONCLUSIONS: Point mutations in the coding sequences of genes encoding RhoA, Rac1, and Cdc42 GTPases do not occur at high frequency in invasive breast and colorectal tumors. PMID- 11768614 TI - Expression of angiogenic factors and tumor progression in human neuroblastoma. AB - PURPOSE: The growth and metastasis of malignant tumors is largely dependent on angiogenesis. Angiogenic factors produced by tumor cells are known to promote tumor angiogenesis. The aim of this study was to investigate which angiogenic factor is the most important in the progression of neuroblastoma (NB). PROCEDURE: The relative expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF-C, basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PD-ECGF/TP) were studied in 28 NB tumor specimens by real-time quantitative reverse transcriptase/polymerase chain reaction (RT-PCR). The relationships between the expression of these four angiogenic factors and stage, patient age, primary site, MYCN copy number, and lymph node metastasis were analyzed. RESULTS: High VEGF-A expression was correlated with stage 4 disease (blood-borne metastasis). No relationship between VEGF-A expression and age, primary site, MYCN copy number, or lymph node metastasis was found. The expression of VEGF-C, bFGF, or PD-ECGF/TP showed no correlation with stage, age, primary site, MYCN copy number, or lymph node metastasis. CONCLUSIONS: Our findings suggest that VEGF-A, but not VEGF-C, bFGF, or PD-ECGF/TP, may be associated with progression of NB. VEGF-A could be a target for antiangiogenic therapy for disseminated NB. PMID- 11768615 TI - Protein phosphorylation: cellular functions and therapeutic perspectives. Tenth colloquium on cellular signal transduction: DKFZ Heidelberg, 9 February 2001. PMID- 11768616 TI - No effect of thromboxane A2 on the attachment of tumor cell lines MDA MB 231, DU145, and U937 to the basement membrane in an in-vitro model. AB - PURPOSE: A broad body of evidence indicates the involvement of P450 TxA2 (thromboxane A2 synthetase) in tumor metastasis formation. A distinct function of the enzyme in this multistep process, however, is still unknown. Therefore the effect of TxA2 (thromboxane A2) on tumor cell adhesion to the basement membrane, a key event in metastasis formation, was investigated. METHODS: A wide variety of compounds designed in our work group and identified as P450 TxA2 inhibitors were applied to several P450 TxA2-positive tumor cell lines to test their influence on tumor cell adhesion. For this purpose an in-vitro basement membrane adhesion model with the matrix gel preparation Matrigel was used. RESULTS: Most of the P450 TxA2 inhibitors tested had no effect on cell adhesion. Although two compounds significantly reduced tumor cell adhesion in a concentration-dependent manner, this was not related to P450 TxA2 inhibition. CONCLUSION: These data indicate that TxA2 might not be involved in the attachment of tumor cell lines to the basement membrane. PMID- 11768617 TI - Keyhole limpet hemocyanin (KLH) conjugate vaccines as novel therapeutic tools in malignant disorders. PMID- 11768618 TI - Clinical results of the ID-KLH vaccination with local GM-CSF in patients with follicular lymphomas (published in Nature Med 1999; 5: 1171-1177) summary of the lecture by L. W. Kwak. PMID- 11768619 TI - Detection of keyhole limpet hemocyanin (KLH)-specific immune responses by intracellular cytokine assay in patients vaccinated with idiotype-KLH vaccine. AB - Keyhole limpet hemocyanin (KLH) has been used as an immune potentiator to enhance antigen-specific responses against haptens and weak antigens including self antigens. In the present study, we describe the optimization of the intracellular cytokine response to KLH in peripheral blood mononuclear cells (PBMC) of lymphoma and myeloma patients that were vaccinated with tumor-specific immunoglobulin (Id) conjugated to KLH. Addition of anti-CD28 antibody significantly enhanced cytokine producing CD4-T cells. While fresh PBMC showed maximal cytokine response 14 h after antigen stimulation, the frozen PBMC showed maximal cytokine responses by 24 h. Supplementation of the culture medium with fetal bovine serum gave a better signal-to-noise ratio than human AB serum in the intracellular detection of cytokines. The intracellular cytokine responses correlated with the cytokine measurements by enzyme-linked immunosorbent assay (ELISA). Together these results indicate that the intracellular cytokine assay is very helpful to measure antigen specific immune responses, and in subsequent studies, we have utilized this sensitive technique to detect immune responses against tumor antigens such as idiotype. PMID- 11768620 TI - Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan Kettering experience. AB - Passively administered and actively induced antibodies have been associated with the eradication of circulating tumor cells and micrometastases in mice and humans. We have identified a series of cell surface carbohydrate and peptide antigens on melanomas, sarcomas, and cancer of the breast, prostate. ovary, and lung tissues. We found that breaking tolerance toward these tumor antigens was best achieved using vaccines containing antigens chemically conjugated to keyhole limpet hemocyanin (KLH) plus a potent immunological adjuvant (QS-21). To date, by using this approach to vaccination. antibodies have been induced in patients against glycolipid antigens GM2, GD2, GD3, FucosylGM1, Globo H, and Lewis Y, and glycoprotein (mucin) antigens Tn, sialyl Tn. TF, and MUC1. More recently, in a comparative study we investigated the T cell response induced by MUCI-KLH conjugates. Although a MUC1-specific T cell response was not consistently detected in any patient, the role of KLH in orienting the cytokine environment was crucial. We were able to confirm that KLH in these conjugate vaccines induces a Th1 T cell response as demonstrated by the high anti-KLH INF-gamma secretion and the IgGI and IgG3 subclasses of this high titer IgG antibodies induced. Clinical trials using KLH conjugated glycolipid and glycoprotein vaccines, are currently ongoing. These range from phase I/II single antigens trials with glycosilated MUC1, polysialic acid, synthetic Fucosyl GMI and GD2, to phase II trials with a polyvalent vaccine containing six or seven antigens. Randomized phase II trials with polyvalent vaccines are planned for initiation in 2001-2002 in patients with ovarian, breast, and prostate cancer. PMID- 11768621 TI - Anti-idiotypic antibody (ab2) vaccines: coupling of Ab2 BR3E4 to KLH increases humoral and/or cellular immune responses in animals and colorectal cancer patients. AB - The colorectal carcinoma (CRC)-associated CO17-1A/GA733 antigen (Ag) has been the target of a phase II/III randomized trial of passive immunotherapy with monoclonal antibody CO17-1A (Ab1), and phase I active immunotherapy trials with polyclonal anti-idiotypic antibodies (Ab2) mimicking the CO17-1A or GA733 epitope of the Ag. However, monoclonal rat Ab2 BR3E4 directed against Ab1 CO17-1A was superior to polyclonal Ab2 in inducing antigen-specific humoral and cellular immune responses in mice and rabbits. Various forms of Ab2 BR3E4, i.e., BR3E4 F(ab')2 precipitated with aluminum-hydroxide (alum), BR3E4-F(ab')2 coupled to KLH and precipitated or non-precipitated with alum, and BR3E4-IgG in alum or incomplete Freund's adjuvant were compared for their capacity to induce in rabbits anti-anti-idiotypic antibodies (Ab3) that specifically bind to the CO17 1A Ag. BR3E4-F(ab')2 coupled to KLH and precipitated with alum was shown to induce the highest Ab3 titers, followed by Ab2 BR3E4-IgG in alum. Therefore Ab2 BR3E4 as intact IgG (IgG group) or as F(ab')2 coupled to KLH (KLH group), was administered in a phase I trial to 45 patients with CRC, stage Dukes'D (UICC stage IV), with the goal to modulate patients' immune responses to their tumors. Fifteen of 23 patients in the IgG group developed Ab3 binding specifically to Ab2, and in four of these patients the Ab3 also specifically bound to Ag-positive CRC cells. Lymphoproliferative responses to Ab2 and/or GA733-2E Ag stimulation were observed in three of these patients. Eighteen of the 22 KLH group patients tested developed Ab3 and the Ab3 bound specifically to CRC cells in eight patients. Five of the 15 KLH group patients tested developed lymphoproliferative responses to Ab2 and/or GA733-2E Ag. Thus, there was a trend for the KLH group demonstrating higher immune response rates than the IgG group. Clinical responses were rare in these patients with liver metastases. PMID- 11768622 TI - Marine tumor vaccine carriers: structure of the molluscan hemocyanins KLH and htH. AB - Keyhole limpet hemocyanin (KLH) is a well-established immune stimulant and hapten carrier, and Haliotis tuberculata hemocyanin (HtH) is a related product. Biologically, KLH and HtH are blue copper proteins which serve as oxygen carriers in the blood of the keyhole limpet Megathura crenulata and the abalone H. tuberculata, respectively, two marine gastropods. Both hemocyanins occur as two distinct isoforms, termed KLH1 KLH2, HtH1, and HtH2. Each of these molecules is based on a very large polypeptide chain, the subunit (molecular mass ca 400 kDa), which is folded into a series of eight globular functional units (molecular mass ca 50 kDa each). Twenty copies of this subunit form a cylindrical quaternary structure (molecular mass ca 8 MDa). This article reviews the recent data on the biosynthesis, quaternary structure, subunit architecture, amino acid sequence, gene structure, and recombinant production of KLH and HtH. PMID- 11768623 TI - Effect of low doses of L-NAME on methamphetamine-induced dopaminergic depletion in the rat striatum. AB - The toxic dose of methamphetamine (METH) (5 mg/kg, s.c., x4, 2 hr intervals) decreased contents of dopamine, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in striatum, and decreased contents of serotonin (5-HT) in both striatum and nucleus accumbens. Administration of low doses of a non selective endothelial and neuronal nitric oxide synthase (NOS) inhibitor, N omega nitro-L-arginine methyl ester (L-NAME) (5 and 10 mg/kg, i.p., x1) intensified the METH-induced decreases in contents of dopamine and its metabolites in striatum. NO substrate, L-arginine (500 mg/kg, i.p., x4) reversed these effects of L-NAME on the METH-neurotoxicity. L-NAME did not change the METH-induced hyperthermia. These findings, which are contrary to our previous study with a high dose of L NAME, suggest that the inhibition of endothelial or neuronal NOS-mediated NO production by low doses of L-NAME enhanced the METH-induced neurotoxicity. The finding that L-NAME can have opposite effects on the METH-neurotoxicity according to the dosing is important, however, additional experiments should be performed to clarify which type of NOS is related to these effects. PMID- 11768624 TI - The effect of low oral doses of (-)-deprenyl and its metabolites on DSP-4 toxicity. AB - Treatment with a single oral dose of (-)-deprenyl (selegiline) before DSP-4 administration could dose-dependently decrease the noradrenaline (NA) depleting effect of the toxin in mouse hippocampus. The maximum protective effect was achieved at as low oral dose as 0.25 mg/kg. Pre-treatment with the same doses of the main metabolites of (-)-deprenyl; (-)-amphetamine and (-)-methylamphetamine provided a weaker attenuation of DSP-4 induced NA depletion, than the parent compound. The selective noradrenergic toxin DSP-4, which depletes NA in nerve terminals originating from the locus coeruleus, is presumably metabolised by CYP 450 enzymes. Continuous administration of low, by themselves non-toxic doses of DSP-4 resulted in the cumulation of its NA depleting effect. PMID- 11768625 TI - Functional regional distribution of histamine receptors in the rat hippocampus: modulation of learning of an active avoidance response. AB - The possible functional regional distribution of the histamine sensitive sites controlling the behavioral performance of learning of an active avoidance response in the hippocampal structure was studied. Adult male rats were stereotaxically implanted with microinjection cannula into three different regions of the hippocampus: the ventral, the dorsal posterior and the dorsal anterior hippocampus. Different groups of rats were microinjected into these subregions with either saline, 9, 45 or 90 nmol of histamine. Five min later all groups were subjected to learning of a conditioned response to an ultrasonic tone warning an electric shock to the feet of the animals. Three sessions of 8 trials were necessary in order to control animals learn the task. Results show that histamine microinjections into the ventral hippocampus were able to significantly inhibit the natural decrease of the latency to escape during trials, impairing the efficiency of learning. Histamine administration into the dorsal posterior hippocampus was slightly effective in prolonging latency and impairing learning, while injections into the dorsal anterior region of the hippocampus had no effect. Results give a further support to the idea that histamine sensitive neurons in the ventral hippocampus are modulating the memory and learning mechanisms in the rat. In addition, evidence has been found suggesting a regional distribution of histamine sensitive neurons controlling learning of avoidance responses along the septo-temporal axis of the rat hippocampus. PMID- 11768626 TI - Neurochemical findings in the MPTP model of Parkinson's disease. AB - Animal models are a very important approach to study the pathogenesis and therapeutic intervention strategies of human diseases. Since many human disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by neurotoxic agents. For instance, the application of the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is able to produce striking similarities to Parkinson's disease (PD) diagnosed in humans. MPTP is thought to selectively damage dopaminergic neurons predominantly those originating in the substantia nigra pars compacta (SNc) which leads to impaired dopaminergic neurotransmission accompanied by a loss of dopaminergic nerve terminals in the striatum. MPTP-induced neurochemical, behavioral, and histopathological alterations replicate very closely the clinical symptoms of PD patients, which will be discussed in this paper and render the MPTP model currently the most favored PD model to study therapeutic intervention strategies in an easy and reliable way in preclinical studies. We and many other research groups propose that the knowledge about the neurotoxic mechanisms of MPTP such as mitochondrial dysfunction with breakdown of energy metabolism and free radical production will help us to understand the underlying mechanisms of PD, which are not fully understood yet. In particular, the novel aspects of inflammatory processes and the involvement of reactive nitrogen species in addition to reactive oxygen species seem to be important milestones for a better understanding of the neurodegenerative effects of MPTP. In this review we focus on the MPTP mouse model which is easy practicable and widely used in neuroscience research and draw comparisons to the human pathology in PD. PMID- 11768627 TI - Functional imaging studies on dopamine and motor control. AB - In this review, the insights that PET and MR activation studies have given us concerning the role of dopamine in motor control are reviewed. Regional cerebral blood flow (rCBF) changes when normal subjects and Parkinson's disease patients perform simple finger movements, motor sequence learning, problem solving, and tasks financially rewarded according to success are compared. Additionally, dopamine release during rewarded and unrewarded actions, as reflected by relative levels of striatal binding of the reversible dopamine antagonist 11C-raclopride, are contrasted. It is argued that during unrewarded familiar actions tonic dopamine release in the basal ganglia acts to focus and filter cortical output so optimising the running of motor programmes. During motor learning, novel, and financially rewarded tasks additional dopamine is phasically released, acting to both alert the subject and to reinforce motor learning. PMID- 11768628 TI - Clinical characteristics of neuroleptic-induced parkinsonism. AB - In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors. PMID- 11768629 TI - High-dose therapy with ropinirole in patients with Parkinson's disease. AB - Ropinirole is effective as mono- and combination therapy in PD. Previous studies have used a maximal dose of 24 mg/day; the present study assesses the effect of higher doses (up to 36 mg/day) on patients with motor fluctuations. Outcome measures were changes in the motor function score of the Unified Parkinson's Disease Rating Scale, the duration of dyskinesias and reductions in levodopa dose. 21/22 patients completed the study. The mean daily ropinirole dose at endpoint was 26.2 mg (SD, 4.43 mg, range 20-36 mg). Improvements in motor function (29%) and the duration of dyskinesias (45%) from baseline to endpoint were significant (p < 0.01 and p < 0.05, respectively). The mean levodopa dose fell by 32% during the study (from 599 mg to 409 mg; p = 0.007). Side effects were mild. High-dose ropinirole (20-36 mg/day) was well tolerated and conferred significant clinical benefit on patients with motor fluctuations. PMID- 11768630 TI - The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia. AB - Patients suffering from Parkinson's disease (PD), often develop dementia (PDD). Their brain histology reveals Alzheimer's disease (AD) like changes and decreased cholin-acetyl transferase (ChAT) activity, in addition to typical PD changes. This cholinergic deficiency has been related to the degree of mental decline. As centrally acting cholinesterase inhibitors (ChEIs) provide cognitive and non cognitive improvement for AD patients, the same therapeutic effect was hypothesized for PDD patients as well. The goal of this study was to assess the effect of ChEIs on both the cognitive and motor state of PDD patients. An open study was conducted. Eleven consecutive PDD patients (M/F 6/5 mean age 75 y) were found eligible for inclusion. They were treated for 26 weeks with tacrine (7 patients) and donepezil (4 patients) as add-on to their regular anti PD drugs. Cognitive assessment was performed at baseline and endpoint by Mini-Mental-State Examination (MMSE) and Alzheimer's-Disease-Assessment-Scale (ADAS-cog). Global Deterioration Scale (GDS) was performed to evaluate active daily living (ADL). Motor evaluation was performed using Short Parkinson Evaluation Scale (SPES) at baseline and end-point. Statistical analysis used Student's paired t-test, ANOVA with repeated measures and Pearson correlation coefficient. ChEIs treated PDD patients showed improvement in their cognitive state. Mean ADAS-cog improved significantly by 3.2 points (p < 0.012). Mean MMSE and GDS improved non significantly by 1.2 and 0.2 points respectively. There was no change in motor function as evident by mean SPES scores, 16.5 at baseline and endpoint. Five individuals actually demonstrated motor improvement under ChEIs. We conclude that ChEIs have a beneficial effect on the cognitive state of PDD patients without aggravating motor function. PMID- 11768631 TI - Cognitive relapse after discontinuation of drug therapy in Alzheimer's disease: cholinesterase inhibitors versus nootropics. AB - In a cross-sectional study of outpatients diagnosed with dementia of the Alzheimer type who had been treated with a broad variety of drugs supposed to improve cognition or to delay cognitive decline, we have investigated the effects of abruptly discontinuing therapy on cognition. Termination of therapy with any cholinesterase inhibitor was associated with a cognitive decline during the following 6-7 weeks which was significantly more pronounced than that experienced by patients who had received nootropic drugs or calcium channel blockers (3.41 vs. 1.17 points on the ADAS-Cog scale; -1.14 vs. -0.06 points on the MMSE scale). This effect was not modified by gender, apolipoprotein E genotype, or the extent of ventricular enlargement on CT scans. Its magnitude was comparable to the cognitive response observed in published clinical trials when cholinesterase therapy commenced, and also with the data obtained during a 6-week placebo washout phase. PMID- 11768632 TI - A study of cranial computer tomograms in very early and early onset schizophrenia. AB - The cranial computer-assisted tomograms of 19 patients suffering from schizophrenic psychoses with onset by age of 14 were examined. The emphasis was on the extent of the inner liquor spaces. Compared to healthy controls, at the beginning of illness a significant enlargement was revealed only in the patient group with very early onset schizophrenia (VEOS, onset prior to the age of 12), whereas children with early onset (EOS, 12 to 14 years of age) showed no significant brain pathology. As a second result, an increase in the extent of the inner liquor spaces seems to correlate with the duration of illness. It is therefore concluded that psychoses interfere with neurodevelopmental processes and cause more severe brain pathology in very young children, already detectable at the onset of the illness. EOS, on the other hand, induces progressive morphological abnormalities over the course of the illness. PMID- 11768633 TI - Soft-tissue haemangioma and periosteal new bone formation on the neighbouring bone. AB - Deeply situated soft-tissue haemangioma sometimes causes periosteal new bone formation on the neighbouring bone. The purpose of this study was to elucidate the aetiological factors for this phenomenon. We studied 25 patients with soft tissue haemangioma on whom plain radiographs and computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations were performed. We examined the presence or absence of periosteal new bone formation, haemangioma-bone distance, size of haemangioma and pain. Periosteal new bone formation was seen in 12 of 25 patients. In these 12 patients, the haemangioma was adjacent to the bone in 11 patients, while the haemangioma-bone distance was 4 mm in the other patient. In the remaining 13 patients who had no periosteal new bone formation, the haemangioma-bone distance was 5-27 mm. Pain in the former group was stronger than that in the latter group, the difference being statistically significant. There was no statistically significant difference in size of haemangioma between the two groups. Therefore, the main factor that induces periosteal new bone formation on the neighbouring bone was not the size of haemangioma, but the distance between the haemangioma and the bone. PMID- 11768634 TI - Intramedullary nailing in humeral shaft fractures. Mechanical behavior in vitro after osteosynthesis with three different intramedullary nails. AB - The aim of this in vitro study was to compare the mechanical behavior of fixation by the Russell-Taylor nail with the more recent Polarus nail. Fixation with an experimental nail made from polyacetal polymer was also included in the study. Thirty humeri were fractured and randomized to receive one of the three nail types. A four-point nondestructive bending test was performed, as well as torsional testing to failure. The torsional test was designed to record the amount of 'play' (uncontrolled rotation) in the bone/implant construct. The Polarus nail gave higher rigidity of the nail/bone construct than the two other types. The Russell-Taylor nailing exhibited a high degree of 'play' (uncontrolled rotation). The polyacetal nails allowed a large elastic deformation before failure. PMID- 11768635 TI - Time-related changes of collected shed blood in autologous retransfusion after total knee arthroplasty. AB - A prospective study was done to determine the changes in blood quality parameters of collected drainage blood in retransfusion systems at 6 and 12 h after surgery to verify whether the blood was still suitable for retransfusion purposes for an additional 6 postoperative hours beyond the so far accepted first 6-h time window after surgery. Eighty-one patients received retransfusion within the first 6 h immediately following total knee arthroplasty. Additionally, drainage blood was collected for another 6 h using the same retransfusion system. Samples for laboratory analysis were taken from both the first and second 6-h blood collection interval. Hemoglobin values increased from 9.6 to 10.4 g dl(-1) (p = 0.021). Platelet counts increased from 65,500 to 80,900 microl(-1) (p < 0.001). Leukocyte counts increased from 5,550 to 8,190 1(-1) (p < 0.001). Lactate dehydrogenase (672 U l(-1) during the first vs 651 U l(-1) during the second collection period) and free hemoglobin (71.7 mg dl(-1) vs 67.0 mg dl(-1)) did not change significantly. The potassium concentration decreased slightly from 4.33 to 4.20 mg dl(-1) (p = 0.002). The lactate concentration increased from 4.44 to 7.21 mg dl(-1) (p < 0.001). The pH decreased from 7.07 to 6.94 (p < 0.001). Interleukin-6 concentration increased from 6,500 to 46,500 ng l(-1) (p < 0.001). In this study, we found no relevant difference in most of the drainage blood quality parameters between the first 6-h collection period and the second 6-h collection with regard to its suitability for autologous retransfusion except higher interleukin-6 levels. Due to the higher interleukin concentration, a possible increase in febrile reactions should be taken into account during retransfusion. PMID- 11768636 TI - Light and electron microscopic study of stress-shielding effects on rat patellar tendon. AB - In this second part of our study, the histomorphologic changes occurring in the patellar tendon (PT) of rats after sole stress-shielding were evaluated. In seven adult albino rats, both PTs were exposed by straight skin incision and then stress-shielded on one side by a cerclage, while the contralateral PT served as the sham-operated control. One animal died after the operation and was used as a negative control. After 10 weeks of otherwise unrestricted motion, the rats were killed, and the histomorphology of all PT specimen pairs compared by light and transmission electron microscopy. Light microscopy showed mid-portion thickening and irregularity of collagen bundles in the stress-shielded tendons. Intense remodelling was demonstrated by increased cellularity and vascularity, as well as by enrichment in acidic proteoglycans. Ultrastructural evaluation and morphometry revealed a predominance of large diameter (peak between 180 and 260 nm) collagen fibrils in the sham-operated controls, while in the stress-shielded tendons the number of apparently new, small-diameter (peak between 40 and 60 nm) collagen fibrils increased (up to 77% per cross-sectional field of view). The difference in peak diameters was statistically significant (p < 0.0005). This rat model demonstrated that sole stress-shielding not only causes biomechanical alterations, but also intense tissue remodelling and significant morphological changes in the collagen fibrils in the patellar tendon, comparable to so-called 'ligamentization' in experimental and clinical patellar tendon grafts for anterior cruciate ligament reconstruction. PMID- 11768637 TI - Pathomorphological and quantitative bacteriological findings in various forms of primary surgery on gunshot wounds of extremities. AB - It is well-known that 'wound excision' is essential in the primary treatment of wounds in war, particularly thorough debridement of the devitalized tissues around the path of a penetrating projectile. Nowadays, the gunshot wounds in peacetime have become prevalent. Instead of the traditional method of 'wound excision' (excision), we used the method of 'incision and drainage' (incision) in the primary surgery of these gunshot wounds of extremities. To determine the treatment effectiveness of these different surgical methods (incision and excision), two groups of dogs were shot in the proximal part of one hind leg with an American M-16 rifle. One group was treated by the method of 'excision'; in the other group 'incision' were performed. No difference in infection rate was noted between the two groups. Similarly, no difference in bacterial count was found between the two groups during the observation period. Also, there was no difference in healing time; the wounds in both groups had healed by 19.2-21.4 days. Microscopic examination revealed a little normal muscle tissue in the necrotic zone of the incision group which might augment the repair process. These results suggest that there are no differences in the effectiveness in preventing infection between the two methods. 'Incision' might be superior to 'excision' for the management of the gunshot wounds of extremities in peacetime, as it involves a simple operation and there are advantages for tissue healing. PMID- 11768638 TI - The association of HLA-DR4 antigen with juvenile chronic arthritis and slipped capital femoral epiphysis. AB - Seventeen children who met the criteria for juvenile chronic arthritis (JCA) were reviewed. Throughout the study, the clinical examination, HLA phenotyping, and radiological assessment of the hips were performed by separate authors who were blinded to other data. At the end of the study, the results were also compared with 25 healthy, age- and sex-matched children. Six of the children with JCA also had radiological signs of slipped capital femoral epiphysis (SCFE; five with minimal slip pattern, one with moderate slip), and five of them had DR4 in their genotypes, in contrast to the remaining 11 patients who did not (p < 0.001). On the other hand, only 2 of 25 children in the control group had DR4 (p < 0.01). The difference was not significant when the patients without SCFE were compared with the control group (p = 1.0). The relative risk of cases with DR4 antigen for SCFE was 57.5, while it was below I for the other antigens. These results suggest that although DR4 is not specific for JCA, it is the common HLA antigen for those who have SCFE, and patients with JCA and HLA-DR4 antigen should be examined for evidence of SCFE, which was not reported before to exist with JCA. PMID- 11768639 TI - Blood loss in anterior cruciate ligament (ACL) reconstruction with and without intercondylar notchplasty: does it affect the clinical outcome? AB - Blood loss is associated with any surgical procedure and should be reduced wherever possible. It was our impression that notchplasty adds to the amount of postoperative bleeding after anterior cruciate ligament (ACL) reconstruction. With posterior placement of the tibial tunnel, notchplasty is optional in many cases. This study aimed to quantify blood loss with and without notchplasty after arthroscopically assisted ACL reconstruction using bone-patellar tendon-bone autografts. We performed a prospective clinical study of 58 patients, who had undergone arthroscopically assisted autogenous patellar tendon ACL reconstruction. In group I, a notchplasty was necessary according to the local anatomical criteria (intraoperative impingement test). In group II, ACL replacement could be performed without notchplasty. Single and total day drainage volume, serum and suction drain hemoglobin (Hb) and hematocrit (Hct) levels were monitored. One year after surgery, the patients were reviewed to assess the outcome according to the IKDC and Lysholm scores and the KT-1000 arthrometer. The total drainage volume was 448 ml (range 150-550 ml) in group I and 299 ml (range 50-420 ml) in group II (p < 0.001). The serum hematocrit (Hct) decrease was 9.7% in group I and 7.4% in group II (p < 0.001). At 12 months after surgery, the IKDC and Lysholm score evaluations and the KT-1000 arthrometer measurements revealed no clinical differences between the notchplasty and non-notchplasty groups. Despite a 30% increase in blood loss, notchplasty has been shown to be a useful procedure to prevent graft impingement without negative side-effects. PMID- 11768640 TI - Rupture of the patellar tendon: a review of 68 cases and a retrospective study of 29 ruptures comparing two methods of augmentation. AB - Rupture of the patellar tendon is a rare injury requiring acute repair to reestablish knee extensor continuity and to allow early motion. Different pathomechanisms have been postulated, and multiple techniques for repair have been described in the literature. Firstly, the current study reviews the epidemiology, pathomechanism, and risk factors. Secondly, we compare the outcome of two augmentation techniques after end-to-end sutures: reinforcement with either a wire cerclage or a PDS cord. In the first part of the study, the medical records of 66 patients with 68 ruptures were reviewed. For the second part, 33 patients were included who had no prior injury to the extensor mechanism of the knee and had suffered an indirect, low-velocity injury followed by immediate repair. Twenty-seven patients with 29 ruptures of the patellar tendon returned for follow-up. Follow-up averaged 8.1 years (range 1-16 years). In the follow-up group, 22 ruptures had augmentation with a wire cerclage (group A), and 7 ruptures had augmentation with a 2-mm PDS cord (group B). Follow-up evaluation consisted of a subjective questionnaire, a physical and radiographic examination, the Hospital for Special Surgery Knee Score, and the Insall-Salvati ratio. Nineteen patients underwent Cybex isokinetic strength testing of the quadriceps. Indirect, low-velocity injuries occurred most often in the 30-40 year age group, whereas complex knee traumas or knee luxations were more evenly distributed. In 10 of 46 patients with an indirect, low-velocity injury, there was a history of prior injury and illness to the extensor mechanism of the knee, compared with 1 of 22 patients with a high-velocity complex knee trauma. In the follow-up group, no patient sustained a rerupture. Two of 22 patients had an extension lag in group A compared with no extension lag in group B. Average flexion in group A was 130 degrees (SD 29 degrees) compared with 137 degrees (SD 12 degrees ) in group B. The average Hospital for Special Surgery Knee Score was 92 (SD 17) in group A and 96 (SD 12) in group B. Three patients were dissatisfied. All had radiographic signs of retropatellar osteoarthritis. In contrast, 9 of 26 patients who were satisfied with their result had radiographic signs of retropatellar osteoarthritis. A postoperative difference in the Insall-Salvati ratio did not correlate with the development of osteoarthritis. Both augmentation techniques are reliable and demostrate good intermediate to long-term results. The outcome did not show significant differences. To avoid reoperation for removal of the cerclage wire, a PDS cord can be used. The infection rate seems to be higher in the PDS group. A larger prospective study group is necessary to determine whether this phenomenon can be reproduced. PMID- 11768641 TI - Tissue response and osteoinduction of human bone grafts in vivo. AB - Freeze-dried human bone allograft is used clinically as an adjunct to autologous bone graft. When freeze-dried human bone allograft is demineralized, the allograft is osteoinductive, since it causes bone to form heterotopically. Both types of allograft are also used alone, such as in spinal fusions, critical size defects, and periodontal therapy. The purpose of this study was to determine the effect of demineralization on the osteoinductive potential of human bone grafts obtained from two different groups of patients. One group consisted of six patients younger than 42 years of age, while the other group consisted of six patients who were older than 70 years of age. The harvested material was lyophilized and divided into two portions, one of which was used directly while the other was demineralized. Osteoinductive ability was established using an in vivo assay for heterotopic bone formation. Activity in these bone grafts was compared with a batch of commercially prepared demineralized, freeze-dried human bone grafts that had been previously shown to be active and another batch that had been shown to display low ('inactive') osteoinductive ability. A bone induction score was determined for each group of grafts based on the number and size of any ossicles formed. In addition, the area of new bone formation and area of residual particles were determined histomorphometrically. Tissue response to the bone grafts varied with donor age and whether the samples had been demineralized or not. Only demineralized, freeze-dried bone graft from patients younger than 42 years of age was osteoinductive; all other batches displayed little or no osteoinductive activity. In the demineralized, freeze-dried bone from donors younger than 42 years of age, the bone induction score and new bone area were significantly higher than in the other batches of bone graft, and the area of residual particles was reduced. Both demineralized and nondemineralized bone graft from patients older than 70 years of age were encapsulated in dense, fibrous connective tissue. These results may help explain the observed differences in clinical outcome when demineralized, freeze-dried bone graft or nondemineralized, freeze-dried bone graft from different donors is used in bone regeneration applications. PMID- 11768642 TI - A minimally invasive percutaneous technique of intramedullary nail insertion in an animal model of fracture healing. AB - Previous animal models of fracture repair have been shown to be reproducible but are often time-inefficient. We present a minimally invasive percutaneous technique for retrograde insertion of intramedullary pins in a model of rat femoral fracture healing. Forty Sprague-Dawley rats were divided into 3 groups: no fracture (n = 6), no fracture but pinned (n = 6), and fractured and pinned (n = 24). The pins were inserted in a percutaneous manner under fluoroscopic control. No incisions were made. All animals tolerated the procedure well and were using the operated leg within hours after the surgery. The mean time for the pinning procedure was 2.3 min (standard deviation 1.1 min). The mean fluoroscopic time for the first 15 procedures was 10 s (standard deviation 4.5 s). The mean fluoroscopic time for the last 15 procedures was 4.2 s (standard deviation 1.2 s). No patellar tendon ruptures or bleeding complications were seen in the postoperative period. The course of fracture healing was not altered by this new percutaneous technique of pin insertion. PMID- 11768643 TI - Periosteal Ewing's sarcoma: radiological imaging and histological features. AB - Periosteal Ewing's sarcoma is very rare. In this report, we describe three cases of periosteal Ewing's sarcoma, illustrating the principal clinical, radiographic, and histologic features. The patients were aged 15, 16, and 20 years old, with an average of 17 years. The tumor occurred in the humerus in two and in the femur in one. Plain radiography showed a laminated periosteal reaction with a Codman's triangle over a subperiosteal soft-tissue mass or saucerization. The unusual site of Ewing's sarcoma was clearly visualized by computed tomography (CT) and magnetic resonance imaging (MRI) and confirmed by histological examination. Chemotherapy and/or irradiation was employed before and after wide excision. The patients have survived an average of 6 years after the primary surgery. PMID- 11768644 TI - Twenty-six-years' survival with multiple bone metastasis of malignant pheochromocytoma. AB - The prognosis of metastatic pheochromocytoma is poor in general. There have been few instances of long-term survival reported. We report a case of a 44-year-old woman who has survived for 26 years after bone metastasis. She was diagnosed as having pheochromocytoma arising in the left adrenal medulla in 1974. Metastasis of pheochromocytoma in the first and third lumbar vertebrae and the right ilium was observed at the same time. The primary lesion was removed, and posterior lumbar spinal fusion was performed for immobilization. The metastatic lesion in the ilium was left untouched. After 26 years, she is well despite a recurrence of the tumors in the skull and a new metastasis in the left abdomen. PMID- 11768645 TI - Natural history of paediatric intervertebral disc calcification. AB - This case report concerns a 5-year-old boy who had intervertebral disc calcification with involvement of two disc spaces and herniation of nucleus pulposus in one. The patient's symptoms resolved completely in a week with conservative measures. At the 4-year follow-up, the child was symptom-free and in full health, the herniation of nucleus pulposus had resolved completely, and calcification had disappeared in one of the disc spaces. Although the cause of this disorder is uncertain, the course is benign and self-limiting, it seldom requires surgical intervention, and the natural history is one of resolution and complete resorption of the calcification. PMID- 11768647 TI - Serial analysis of gene expression in a single cell. PMID- 11768646 TI - Deep soft-tissue leiomyoma of the popliteal fossa in a 14-year-old girl. AB - This is the first case report of a deep soft-tissue leiomyoma with intraarticular localization within the knee joint. A 14-year-old girl presented with a painless mass in the dorsal aspect of her knee which she had noticed some 9 months earlier. While on plain radiographs no bony lesions were visible, magnetic resonance imaging (MRI) revealed an intraarticularly located tumor with well defined margins. Intraoperatively, the tumor was found adjacent to the posterior cruciate ligament. The final diagnosis was established immunohistologically. Although this is a very rare tumor, it has to be considered in the differential diagnosis for soft-tissue swellings of the popliteal fossa. PMID- 11768648 TI - Modification of the Boyden chamber to improve uniformity of cell invasion of matrigel-coated membranes. PMID- 11768649 TI - Plasmid construction by linker-assisted homologous recombination in yeast. PMID- 11768650 TI - 18S ribosomal RNA detection on Northern blot employing a specific oligonucleotide. PMID- 11768651 TI - Isopropyl-beta-D-thiogalactosidase (IPTG)-inducible tyrosine phosphorylation of proteins in E. coli. PMID- 11768652 TI - Small broad-host-range lacZ operon fusion vector with low background activity. PMID- 11768653 TI - Optimized insect cell culture for the production of recombinant heterologous proteins and baculovirus particles. PMID- 11768654 TI - Ploidy determination in insects. PMID- 11768655 TI - Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy. PMID- 11768656 TI - Vectors for the expression of tagged proteins in Drosophila. AB - Regulated expression systems have been extremely useful in developmental studies, allowing the expression of specific proteins in defined spatial and temporal patterns. If these proteins are fused to an appropriate molecular tag, then they can be purified or visualized without the need to raise specific antibodies. If the tag is inherently fluorescent, then the proteins can even be visualized directly, in living tissue. We have constructed a series of P element-based transformation vectors for the most widely used expression system in Drosophila, GAL4/UAS. These vectors provide a series of useful tags for antibody detection, protein purification, and/or direct visualization, together with a convenient multiple cloning site into which the cDNA of interest can be inserted. PMID- 11768658 TI - Differentiating vector-derived mRNA from contaminating DNA templates by inverse RT-PCR. AB - Inverse RT-PCR was used for detecting doxycycline-induced mRNA expression after viral transduction with a retroviral vector harboring human TDAG51. After the circularization of double-stranded cDNA, induced transcripts originating from integrated vector genomes were selectively amplified, even in the presence of DNA templates. Thus, DNase treatment before amplification was unnecessary. PMID- 11768657 TI - Reverse transcription slippage over the mRNA secondary structure of the LIP1 gene. AB - The secondary structures in mRNA often cause early termination during the synthesis of cDNA. In an attempt to determine the 5'-untranslated region (UTR) of the gene LIP1 using the RNA ligase-mediated rapid amplification of cDNA ends (RLM RACE), we found that reverse transcriptases skipped over the LIP1 RNA secondary structures and continued the DNA synthesis through RNA adapter sequences without early termination. A fragment of only three nucleotides upstream of the LIP1 translation initiation codon was obtained from the initial RACE-PCR, which was much shorter than the 57-nucleotide fragment obtained from the cDNA library screening. Analysis of the 5' end sequence indicates the presence of high G+C content and stem-loop secondary structures. Therefore, optimizations of the reaction with high temperature (70 degrees C) and a thermostable reverse transcriptase were performed to synthesize the first-strand cDNA, which was determined to have 73 nucleotides in the 5'-UTR. These results suggest that, under cDNA synthesis conditions at 42 degrees C and 60 degrees C, the reverse transcriptases skipped over the stem-loop structures of LIP1 mRNA and continued the cDNA synthesis until they reached the RNA adapter sequences. Thisfinding draws attention to adopting optimized conditions for cDNA synthesis on G+C-rich RNA templates. PMID- 11768659 TI - Molecular Biocomputing Suite: a word processor add-in for the analysis and manipulation of nucleic acid and protein sequence data. AB - In all fields of molecular biology, researchers are increasingly challenged by experiments planned and evaluated on the basis of nucleic acid and protein sequence data generally retrieved from public databases. Despite the wide spectrum of available Web-based software tools for sequence analysis, the routine use of these tools has disadvantages, particularly because of the elaborate and heterogeneous ways of data input, output, and storage. Here we present a Visual Basic-encoded Microsoft Word Add-In, the Molecular BioComputing Suite (MBCS), available at the BioTechniques Software Library (www.BioTechniques.com). The MBCS software aims to manage and expedite a wide range of sequence analyses and manipulations using an integrated text editor environment including menu-guided commands. Its independence of sequence formats enables MBCS to be used as a pivotal application between other software tools for sequence analysis, manipulation, annotation, and editing. PMID- 11768660 TI - Telometric: a tool providing simplified, reproducible measurements of telomeric DNA from constant field agarose gels. PMID- 11768661 TI - Increased throughput for fragment analysis on an ABI PRISM 377 automated sequencer using a membrane comb and STRand software. AB - This manuscript outlines our protocol for using a freely downloadable fragment analysis software package (STRand) together with a 96+4 RapidLoad membrane comb to increase throughput of samples for fragment analysis on ABI sequencers without costly upgrades from the manufacturer. We outline how using these products allows one to score 90 lanes of sample per gel on an ABI PRISM 377XL (64-lane sequencer), saving both time and money in the processing of samples. This protocol is a major modification to those suggested by the manufacturer. This protocol gives more consistent results that are easier to score than standard protocols, and it reduces reagent costs. Interest in fragment analysis (primarily microsatellites and AFLPs) is steadily increasing among both population ecologists and geneticists, and methods that simultaneously increase sample throughput while reducing costs associated with these analyses by over 50% per gel should prove useful to anyone using an ABI, MJ Basestation, or LI-COR automated sequencer for fragment analysis. PMID- 11768662 TI - Set of novel tools for PCR primer design. AB - We have developed a new package of computer programs and algorithms for different PCR applications, including allele-specific PCR, multiplex PCR, and long PCR. The package is included in the upcoming VectorNTI suite software and attempts to incorporate most of the current knowledge about PCR primer design. A wide range of primer characteristics is available for user manipulation to provide improved efficiency and increased flexibility of primer design. To accelerate the primer calculations, we have optimized algorithms using recent advances in computer science such as dynamic trees and lazy evaluation. Proper structural organization of input parameters provides further program acceleration. New Vector NTI primer design software allows calculations of primer pairs for long PCR amplification of 120-kb genomic DNA in 5 min under most stringent input parameters and clustering 435 primer pairs for multiplex PCR within 30 min on a standard Pentium III PC. Our program allows the user to take advantage of molecule annotation by applying different kinds of filtering features during PCR primer design. PMID- 11768663 TI - Miniaturized electrophoresis: an evolving role in laboratory medicine. AB - The promise of capillary electrophoresis (CE) for supplanting conventional methods in the clinical laboratory led to intense interest in this analytical tool a decade ago. Since then, a number of clinical applications have been defined along with those that have impacted the pharmaceutical, environmental, and forensic arenas. Concurrent with the development of CE applications was the emergence of electrophoresis in the microchip format. The main attraction of this platform, the ability to execute high-resolution separations in a few hundred seconds, was not its only attribute. The capability for parallel processing of separations was complemented by the potentialfor integrating sample preparation into the same device. This Review highlights recent progress towards CE and microchip electrophoresis as clinical diagnostic tools, with literature coverage from 1996 to 2000. PMID- 11768664 TI - Methylation analysis of formalin-fixed, paraffin-embedded sections using a nontoxic DNA extraction protocol. PMID- 11768665 TI - Statistical validation of the mammaglobin-nested RT-PCR assay for tumor cell detection in blood of breast cancer patients. AB - A stochastic model was developed to validate the results obtained with the mammaglobin-nested RT-PCR assay for tumor cell detection in peripheral blood of breast cancer patients. Since the assay consists of four PCR setups per peripheral blood sample, the probabilities for receiving 0, 1, 2, 3, or 4 positive setups were calculated. In this model, samples with just 500 mammaglobin mRNA molecules are highly probable to result in at least three positive setups, whereas lower quantities shift the probabilities towards one or two positive setups. In the clinical trial, samples with one or two mammaglobin positive setups were detected in 6/143 (4%) patients with benign lesions of the breast, in 41/310 (13%) breast cancer patients with no evidence of disease and in 39/157 (25%) breast cancer patients with metastatic disease. On the contrary, no sample from patients with benign lesions of the breast resulted in three or four positive setups, but 5/310 (2%) breast cancer patients with no evidence of disease and 46/157 (29%) with metastatic disease. These results correspond with the model: an increased number of tumor cells in peripheral blood lead to a higher amount of mammaglobin mRNA molecules, and these samples may result in at least three positive setups. Samples with three orfour positive setups were mainly derived from breast cancer patients with metastatic disease and only occasionally from patients with no evidence of disease. On account of these results, samples with at least three positive setups are of prognostic value and regarded as tumor cell positive. PMID- 11768666 TI - Consensus PCR and microarray for diagnosis of the genus Staphylococcus, species, and methicillin resistance. AB - We propose the use of DNA microarray for the discrimination of homologous products after a single PCR amplification with consensus primers. The method was applied to Staphylococcus identification. The femA nucleotide sequences, which are phylogenetically conserved among the staphylococci, were first amplified using a consensus primer pair together with the mecA sequence, a molecular marker for methicillin resistance. Products were then identified on a glass array. The microarray contained five selective DNA capture probes for the simultaneous and differential identification of the five most clinically relevant staphylococcal species (S. aureus, S. epidermidis, S. haemolyticus, S. hominis, and S. saprophyticus), while a consensus capture probe could detect all femA sequences, allowing the identification of the genus Staphylococcus. The mecA sequence hybridized to a specific capture probe. The identification was univocal because only a single capture probe had to be present for each sequence to be identified. The hybridization and identification processes were completed in less than 2 h. Current results demonstrate that low-density microarrays are powerful multigenotypic post-PCR analyzers and could compete with conventional bacteria identification. PMID- 11768667 TI - Multiplex automated primer extension analysis: simultaneous genotyping of several polymorphisms. AB - Accurate and fast genotyping of single nucleotide polymorphisms (SNPs) is of significant scientific importance for linkage and association studies. We report here an automated fluorescent method we call multiplex automated primer extension analysis (MAPA) that can accurately genotype multiple known SNPs simultaneously. This is achieved by substantially improving a commercially available protocol (SNaPshot). This protocol relies on the extension of a primer that ends one nucleotide 5'of a given SNP with fluorescent dideoxy-NTPs (minisequencing), followed by analysis on an ABI PRisMS 377 Semi-Automated DNA Sequencer Our modification works by multiplexing the initial reaction that produces the DNA template for primer extension and/or multiplexing several primers (corresponding to several SNPs) in the same primer extension reaction. Then, we run each multiplexed reaction on a single gel lane. We demonstrate that MAPA can be used to genotype up to four SNPs simultaneously, even in compound heterozygote samples, with complete accuracy (based on concordance with sequencing results). We also show that primer design, unlike the DNA template purification method, can significantly affect genotyping accuracy, and we suggest useful guidelines for quick optimization. PMID- 11768668 TI - Rapid competitive PCR using melting curve analysis for DNA quantification. AB - A rapid competitive PCR method was developed to quantify DNA on the LightCycler. It rests on the quantitative information contained in the melting curves obtained after amplification in the presence of SYBR Green I. Specific hybridization probes are not required. Heterologous internal standards sharing the same primer binding sites and having different melting temperatures to the natural PCR products were used as competitors. After a co-amplification of known amounts of the competitor with a DNA-containing sample, the target DNA can be quantified from the ratio of the melting peak areas of competitor and target products. The method was developed using 16S rDNA fragments from Streptococcus mutans and E. coli and tested against existing PCR-based DNA quantification procedures. While kinetic analysis of real-time PCR is well established for the quantification of pure nucleic acids, competitive PCR on the LightCycler based on an internal standardization was found to represent a rapid and sensitive alternative DNA quantification method for analysis of complex biological samples that may contain PCR inhibitors. PMID- 11768669 TI - Progress and outcomes for children with autism receiving parent-managed intensive interventions. AB - Parent-managed behavioral interventions for young children with autism are under researched. We analyzed data from 66 children served by 25 different early intervention consultants. After a mean of 31.6 months of intervention IQ scores had not changed (N = 22). Vineland adaptive behavior scores had increased significantly by 8.9 points (N = 21). No children aged > 72 months attained normal functioning, i.e., IQ > 85 and unassisted mainstream school placement (N = 42). Progress for 60 children across 12 months was found for mental age (5.4 months), adaptive behavior (9.7 months), and language (5.1 months). The interventions did not reproduce results from clinic-based professionally directed programs. The effectiveness of the parent-managed intervention model as it has developed and the adequacy of professional services in that model are discussed. PMID- 11768670 TI - The effects of progressive relaxation training on the disruptive behavior of a boy with autism. AB - This study examined the effects of progressive relaxation training on the disruptive behaviors of a boy with autism. Moreover, his overt relaxed behaviors before and after relaxation training were measured using the Behavioral Relaxation Scale (Poppen, 1988, Poppen, 1998). After the participant received training in progressive relaxation procedures a multielement design with three conditions was utilized to determine the effects of the procedures on the duration of the boy's disruptive behaviors during leisure activity sessions. The conditions were: (a) relaxation prior to a leisure activity session; (b) cued relaxation; and (c) no relaxation prior to the session, which represented a baseline condition. Results indicated that the participant acquired progressive relaxation skills, displayed more relaxed behaviors after performing the procedures, and showed a decrease in the duration of his disruptive behaviors upon completing progressive relaxation training prior to a leisure activity session. Implications for future research are discussed. PMID- 11768671 TI - Integrating behavioral and pharmacological interventions in treating clients with psychiatric disorders and mental retardation. AB - While the literature on treatment of dually diagnosed individuals continues to grow, few studies have examined the potential interactions between behavioral interventions and pharmacological interventions in treating persons with a developmental disability and a concurrent psychiatric disorder. The current theoretical paper discusses different manners in which psychotropic medications and behavioral interventions can interact, including the potential for facilitative or inhibitory effects of one treatment modality on the other. Possible permutations of these interactions are discussed. Case examples, including objective measures of psychiatric and behavioral symptoms over time, representing possible illustrations of these permutations, are presented. The authors argue that in many cases the potential effect of one treatment procedure on the efficacy of another may be an important consideration in treating dually diagnosed individuals. PMID- 11768672 TI - Environmental opportunities and supports for exercising self-determination in community-based residential settings. AB - Information was collected on the environmental opportunities for exercising self determination among 281 adults with mental retardation receiving community-based residential supports. The results indicated that: (1) the majority of participants had little or no opportunity to exercise self-determination over major life decisions (e.g., with whom and where to live, the recruitment and retention of care staff); (2) even in more mundane areas, such as where and when to eat, the majority of participants were not supported to exercise effective control; (3) variation in environmental opportunities to exercise self determination was strongly related to a range of factors including participant ability, previous residential history, and structural and procedural aspects of the residential supports currently provided. PMID- 11768673 TI - The relationship of social skills as measured by the MESSIER to rumination in persons with profound mental retardation. AB - Fifty-two persons with profound mental retardation; 26 people with rumination and 26 controls were studied. The Matson Evaluation of Social Skills for Individuals with sEvere Retardation (MESSIER) was administered to all subjects. Groups were compared across each of six subcategories; positive verbal, positive nonverbal, general positive, negative verbal, negative nonverbal, and general negative items. Controls scored significantly better on the general positive subscale than persons with rumination, although no differences in negative behaviors was noted across groups. Implications of these data are discussed. PMID- 11768674 TI - Learning curves for breast cancer sentinel lymph node mapping based on surgical volume analysis. AB - BACKGROUND: Implementation of new procedures, including lymphatic mapping for breast cancer, must be done and overseen by the medical community in a responsible way to ensure that the procedures are performed correctly. This study addresses the issues of adequacy of training and certification of surgeons performing lymphatic mapping. Ensuring quality in surgical care requires outcomes measures that are described in this study. STUDY DESIGN: Sixteen surgeons performed lymphatic mapping in 2,255 patients with breast cancer using a combination blue dye and Tc99m-labeled sulfur colloid to identify the sentinel lymph nodes (SLNs). All participants were trained in a 2-day CME-accredited course. The Cox learning curve model (total number of mapping failures/total number of mapping cases) for a consecutive series of lymphatic mapping cases is described. The relationship of the Surgical Volume Index, the cases performed in a 30-day period, to the failure rate for each surgeon was modeled as a logistic regression curve (y = e(a+bx)/[1 + e(a+bx)]). RESULTS: Surgeons performing less than three SLN biopsies per month had an average success rate of 86.23% +/- 8.30%. Surgeons performing three to six SLN biopsies per month had a success rate of 88.73% +/- 6.36%. Surgeons performing more than six SLN biopsies per month had a success rate of 97.81% +/- 0.44%. CONCLUSIONS: This experience defines a learning curve for lymphatic mapping in breast cancer patients. Data suggest that increased volumes lead to decreased failure rates. These data provide surgeons performing SLN biopsy with a new paradigm for assessing their skill and adequacy of training and describes the relationship between volume of cases performed and success rate of SLN detection. PMID- 11768675 TI - Lymphoscintigraphic anatomy of sentinel lymphatic channels after subareolar injection of Technetium 99m sulfur colloid. AB - BACKGROUND: Injection of Technetium 99m sulfur colloid (Tc-99m-SC) into the subareolar lymphatic plexus provides a rapid and reliable method of identifying breast sentinel lymph nodes and their lymphatic connections to the areola, termed sentinel lymphatic channels (SLCs). The objective of this study was to define the anatomic origin, number, and direction of the SLC in relation to the areola after subareolar injection of Tc-99m-SC. STUDY DESIGN: Using a hand-held goniometer, the exit angle (theta(e)) and direction from the vertical (to the patient's right or left) of SLCs were determined in 87 successful preoperative lymphoscintigrams (46 left breast and 41 right breast). RESULTS: One major lymphatic trunk was identified in 91% of cases (n = 79), and two lymphatic trunks were identified in 9% of cases (n = 8). Overall, 24% (n = 21) of major lymphatic trunks exited the areola vertically (theta(e) = 0 degrees), 33% (n = 29) exited the areola with theta(e) = right or left 1 to 30 degrees, and 32% (n = 28) exited with a theta(e) = right or left 31 to 60 degrees. In total, 90% (n = 78) of SLCs exited the areola with a theta(e) = right or left 0 to 60 degrees, equivalent to 10 to 12 o'clock in the right breast, and 12 to 2 o'clock in the left breast. CONCLUSIONS: Radial angular measurements of SLCs from preoperative lymphoscintigrams performed by SA injection confirm that the origin of the majority of SLCs is within the upper, outer edge of the areola, and that all SLCs ultimatelytraverse the upper, outer quadrant of the breast and terminate on axillary sentinel nodes. PMID- 11768676 TI - Diagnosis of acute cholecystitis: sensitivity of sonography, cholescintigraphy, and combined sonography-cholescintigraphy. AB - BACKGROUND: Radiographic diagnosis of acute cholecystitis can be established using ultrasonography (US), cholecystoscintigraphy (HIDA), or both. Although both modalities have been effective in diagnosing acute cholecystitis (AC), physicians from the emergency department and admitting surgeons continue to request both tests in an attempt to increase the diagnostic accuracy of AC. This article reports the institutional experience of a large tertiary care health care facility, with respect to the sensitivity of US, HIDA, and combined US and HIDA. STUDY DESIGN: We conducted a retrospective review of 132 patients diagnosed with AC who underwent laparoscopic cholecystectomy during the same hospitalization. Patients were stratified into three groups: Group 1 (Gp1, n = 50) included patients who underwent US alone, group 2 (Gp2, n = 28) included patients who underwent HIDA scan alone, and group 3 (Gp3, n = 54) included patients who underwent both US and HIDA. RESULTS: The three groups did not differ with respect to age, liver chemistry, time to operation, and hospital length of stay. The sensitivity of US, HIDA, and combined US/HIDA as diagnostic modalities for acute cholecystitis was referenced to histopathologic confirmation. Sensitivity was 24 of 50 (48%), 24 of 28 (86%), and 49 of 54 (90%) for US, HIDA, and the combination of US/HIDA, respectively. CONCLUSIONS: HIDA scan is a more sensitive test than US in diagnosing patients with AC. Based on the results of this study, we recommend that HIDA scan should be used as the first diagnostic modality in patients with suspected acute cholecystitis; US should be used to confirm the presence of gallbladder stones rather than to diagnose AC. PMID- 11768677 TI - Laparoscopic cholecystectomy and choledocholithotomy in patients with a previous gastrectomy. AB - BACKGROUND: An increased incidence of cholelithiasis has been widely reported after truncal vagotomy and after gastric resection. In the early phase of patient selection, previous gastrectomy has been considered a relative contraindication to laparoscopic cholecystectomy (LC). In this study, we examined the management of LC in patients with previous gastrectomy. STUDY DESIGN: LC was attempted on 1,260 consecutive patients. Of these patients, 29 had a previous gastrectomy. Surgical procedures that had been performed included Billroth I gastrectomies (15), Billroth II gastrectomies (10), and total gastrectomies (4). There were 23 cases of cholelithiasis, 4 chronic cholecystitis, 2 gallbladder polyps, I porcelain gallbladder, and I gallbladder cancer. Nine patients were diagnosed with stones in their common bile duct or common hepatic duct. RESULTS: Preoperatively, seven of nine patients with common bile duct stones were subjected to endoscopic sphincterotomy, and the stones were removed successfully from five of these patients. In the remaining two patients, common bile duct stones were removed by laparoscopic choledocholithotomy by choledochotomy. The LC was completed in 26 patients (90%) who had undergone previous gastrectomy. In 449 patients who had previous abdominal surgery without a gastrectomy, only 4 patients (0.9%) required open surgery. In contrast, three patients (10%) with previous gastrectomy required open surgery. No major complications were recorded in this study series, and no residual or retained stones were seen during a followup period of 3 months. CONCLUSIONS: Clear visualization of anatomic structures and landmarks, and scrupulous hemostasis are needed to perform a safe LC in these patients. We conclude that in our study patients, a previous gastrectomy is considered an indication for LC and laparoscopic choledochotomy. PMID- 11768678 TI - Peritoneal washings are not predictive of occult peritoneal disease in patients with hilar cholangiocarcinoma. AB - BACKGROUND: Evaluation of peritoneal cytology provides valuable staging information in patients with gastric and pancreatic adenocarcinoma, but its usefulness in patients with extrahepatic cholangiocarcinoma is unclear. The aim of this study was to evaluate the predictive value of peritoneal cytology in patients with potentially resectable hilar cholangiocarcinoma. This study evaluated a possible association between positive peritoneal cytology and percutaneous transhepatic biliary drainage, which is commonly used in these patients and may result in peritoneal biliary leakage and peritoneal seeding. STUDY DESIGN: From October 1997 through June 2000 26 patients with hilar cholangiocarcinoma underwent staging laparoscopy immediately before planned open exploration and resection. Peritoneal washings were obtained during laparoscopic examination before any biopsies were taken. Cytologic analysis was performed using the Papanicolau technique. RESULTS: There were 18 men and 8 women, with a median age of 69 years (range 42 to 81 years). The most common presenting symptom was jaundice (n = 19). Previous biliary drainage was performed in 23 patients: 9 percutaneous and 14 endoscopic. Metastatic disease was suspected preoperatively in six patients, three to the liver, two to the peritoneum, and one to regional lymph nodes, all of which were confirmed at laparoscopy. Laparoscopy identified five additional patients with metastatic disease. Peritoneal cytology was positive for malignant cells in two patients, both of whom had gross peritoneal metastases. Nine other patients had metastatic disease to distant sites within the abdomen, but none had positive cytology. Overall, six patients had metastatic disease to the peritoneal cavity, only one of whom had undergone earlier percutaneous biliary drainage. CONCLUSIONS: Peritoneal cytology was not predictive of occult metastatic disease. Laparoscopic staging identified some patients with unresectable hilar cholangiocarcinoma, but analysis of peritoneal cytology provided no additional information. There was no association between percutaneous transhepatic biliary drainage and peritoneal tumor seeding. PMID- 11768679 TI - Bowel resection at the time of primary cytoreduction for epithelial ovarian cancer. AB - BACKGROUND: The purpose of this study was to determine the morbidity and survival associated with bowel resection at the time of primary cytoreductive surgery for ovarian cancer. STUDY DESIGN: We reviewed all patients undergoing bowel resection by gynecologic oncology faculty at the time of primary cytoreduction for advanced epithelial ovarian cancer diagnosed between 1983 and 1995. RESULTS: There were 105 patients meeting the above criteria. The median age was 65 years (range 34 to 85 years). There were 76 stage III and 25 stage IV cancers. The primary indication for bowel resection was tumor debulking in 92% of the patients. Seventy patients had segmental resection of the colon only, and 22 patients underwent resections that included the large and small bowels. Mean operating time was 260 minutes and mean estimated blood loss was 1,447 mL. Thirty-three (31%) patients were optimally cytoreduced to less than 1 cm residual disease. Ten patients experienced major complications directly related to bowel resection, including bowel fistula (4 patients), early postoperative bowel obstruction (5 patients), and stomal hernia (1 patient). Other morbidity included ileus for more than 10 days (18 patients), cardiac complications (17 patients), pneumonia (8 patients), sepsis (5 patients), and thromboembolism (4 patients). Six patients died and five patients required reexploration within 30 days of operation. Patients with preoperative bowel obstruction and suboptimal residual disease were more likely to have postoperative morbidity. Median survival in the optimally debulked patients was 35 months compared with 18 months in patients suboptimally cytoreduced (p = 0.006). Multivariate analysis demonstrated that optimal debulking (p = 0.009) and platinum chemotherapy (p = 0.00006) were independently associated with improved survival. Age, International Federation of Gynecologia Oncologists stage, American Society of Anesthesiologists class, and paclitaxel chemotherapy did not influence survival. CONCLUSIONS: In patients undergoing bowel resection at the time of primary cytoreduction for ovarian cancer, optimal cytoreduction to less than 1 cm residual disease results in improved survival. Morbidity is common but is comparable to other published series of ovarian cancer patients undergoing primary cytoreductive surgery without bowel resection. Additionally, patients with preoperative bowel obstruction and suboptimal residual disease are more likely to have serious morbidity. PMID- 11768680 TI - What's new in colon and rectal surgery. PMID- 11768681 TI - What's new in orthopaedic surgery. PMID- 11768682 TI - The surgical management of pituitary adenomas in a series of 3,093 patients. PMID- 11768683 TI - Are surgery training programs ready for virtual reality? A survey of program directors in general surgery. AB - BACKGROUND: The use of advanced technology, such as virtual environments and computer-based simulators (VR/CBS), in training has been well established by both industry and the military. In contrast the medical profession, including surgery, has been slow to incorporate such technology in its training. In an attempt to identify factors limiting the regular incorporation of this technology into surgical training programs, a survey was developed and distributed to all general surgery program directors in the United States. STUDY DESIGN: A 22-question survey was sent to 254 general surgery program directors. The survey was designed to reflect attitudes of the program directors regarding the use of computer-based simulation in surgical training. Questions were scaled from 1 to 5 with 1 = strongly disagree and 5 = strongly agree. RESULTS: A total of 139 responses (55%) were returned. The majority of respondents (58%) had seen VR/CBS, but only 19% had "hands-on" experience with these systems. Respondents strongly agreed that there is a need for learning opportunities outside of the operating room and a role for VR/CBS in surgical training. Respondents believed both staff and residents would support this type of training. Concerns included VR/CBS' lack of validation and potential requirements for frequent system upgrades. CONCLUSIONS: Virtual environments and computer-based simulators, although well established training tools in other fields, have not been widely incorporated into surgical education. Our results suggest that program directors believe this type of technology would be beneficial in surgical education, but they lack adequate information regarding VR/CBS. Developers of this technology may need to focus on educating potential users and addressing their concerns. PMID- 11768684 TI - The management of the unknown primary. PMID- 11768685 TI - Perioperative stress dose steroids: do they make a difference? PMID- 11768686 TI - Chronic pain management and the surgeon: barriers and opportunities. PMID- 11768687 TI - Peristomal pyoderma gangrenosum. PMID- 11768688 TI - Thoracoscopic extraction of a Dobbhoff feeding tube knotted in the pleural space. PMID- 11768689 TI - Ultrasound-guided liver subsegmentectomy: the peculiarity of segment 4. PMID- 11768690 TI - Surgical approach to internal mammary lymph node biopsy. PMID- 11768691 TI - Bedside carbon dioxide cavography. PMID- 11768692 TI - Safety of liver transection before mobilization. PMID- 11768693 TI - Noncalculous biliary obstruction in children and adolescents. PMID- 11768694 TI - Obstructing colorectal cancers. PMID- 11768695 TI - Revision thyroplasty. AB - To document surgical techniques for performing a revision thyroplasty operation and to describe the subjective and objective results of these operations. I undertook a retrospective review of all patients who have undergone thyroplasty in my practice. I identified patients who required revision of a previous thyroplasty and evaluated preoperative and postoperative video and audio analyses of the voice. I identified the surgical steps necessary for successful completion of a revision operation and noted any special findings made at surgery. Charts were reviewed and tabulated for reasons for failure of the first operation, efficacy of the second surgical approach, specific anatomic findings made at revision surgery, and types of surgery available for revision. Of 625 total thyroplasties in 331 patients, revision operations accounted for 61 operations in 48 patients. All thyroplasty operations were found to be revisable or reversible. Objective voice analysis for 35 operations in 32 patients revealed a statistically significant improvement in shimmer in women, and in harmonics-to noise ratio in all patients. Subjective voice improvement occurred in 80% of patients after revision surgery. I conclude that revision thyroplasty is possible with all thyroplasty types, giving significant improvement in both shimmer (women) and harmonics-to-noise ratio (all patients). Although most voices are still abnormal on postoperative objective voice analysis, 80% of patients are subjectively improved. PMID- 11768696 TI - Safety and efficacy of transcervical resection of parapharyngeal space neoplasms. AB - There are several surgical approaches for resection of parapharyngeal space (PPS) neoplasms. The purpose of this study was to evaluate local disease control, facial nerve injury, and need for mandibulotomy associated with resection of PPS neoplasms via the transcervical approach with submandibular gland excision. A retrospective chart review of 33 patients who underwent resection of a PPS neoplasm between October 1991 and July 2000 was performed. Of the 33 patients, 3 patients developed local recurrence after a median follow-up of 24 months. None of the patients experienced facial nerve paresis or paralysis. Three patients (9.1%) required a mandibulotomy for further exposure. This study demonstrated that the transcervical approach with submandibular gland excision for resection of PPS neoplasms provides excellent local disease control with minimal risk of facial nerve injury or need for mandibulotomy and/or tracheotomy. PMID- 11768697 TI - Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. AB - Esophageal epithelium has intrinsic antireflux defenses, including carbonic anhydrases (CAs I to IV) that appear to be protective against gastric reflux. This study aimed to investigate the expression and distribution of CA isoenzymes in laryngeal epithelium. Laryngeal biopsy specimens collected from the vocal fold and interarytenoid regions were analyzed by Western blotting and immunofluorescence. Carbonic anhydrases I and II were expressed by the majority of samples analyzed. In contrast, CA III was differentially expressed in the interarytenoid samples and was not detected in any vocal fold samples. The expression of CA III was increased in esophagitis as compared to normal esophageal tissue. Carbonic anhydrase I and III isoenzymes were distributed cytoplasmically in the basal and lower prickle cell layers. The laryngeal epithelium expresses some CA isoenzymes and has the potential to protect itself against laryngopharyngeal reflux. Laryngeal tissue may be more sensitive to injury due to reflux damage than the esophageal mucosa because of different responses of CA isoenzymes. PMID- 11768698 TI - Surgery for pediatric subglottic stenosis: disease-specific outcomes. AB - To set the foundation to develop a disease-based, operation-specific model to predict the outcome of pediatric airway reconstruction surgery, we performed a retrospective database review of children operated on at a single, tertiary-care children's hospital. Over the 12-year period 1988 to 2000, a total of 1,296 airway reconstruction procedures were performed. Out of these, charts were identified for 199 children who underwent laryngotracheal reconstruction for a sole diagnosis of subglottic stenosis. Children were excluded from the study if their disorder included supraglottic, glottic, or upper tracheal disease. The main outcome measures were Myer-Cotton grade-specific decannulation and extubation rates, including both operation-specific and overall results. There were 101 children who underwent double-stage laryngotracheal reconstruction. The operation-specific decannulation rates for Myer-Cotton grades 2, 3, and 4 were 85% (18/21), 37% (23/61), and 50% (7/14) (chi2 analysis, p = .0007). The overall decannulation rates were 95% (20/21), 74% (45/61), and 86% (12/14) (chi2 analysis, p = .04). There were 98 children who underwent single-stage laryngotracheal reconstruction. The operation-specific extubation rates for Myer Cotton grades 2, 3, and 4 were 82% (37/45), 79% (34/43), and 67% (2/3) (chi2 analysis, p = .63). The overall extubation rates were 100% (45/45), 86% (37/43), and 100% (3/3) (chi2 analysis, p = .03). Logistic regression analysis showed no effect of age (less than or greater than 2 years of age) on operation-specific or overall outcome parameters. We conclude that laryngotracheal reconstruction for pediatric subglottic stenosis remains a challenging set of procedures in which multiple operations may be required to achieve eventual extubation or decannulation. Children with Myer-Cotton grade 3 or 4 disease continue to represent a significant challenge, and refinements of techniques are being examined to address this subset of children. Disease-based, operation-specific outcome statistics are the first step in the development of a meaningful predictive model. PMID- 11768699 TI - Esophageal motor function in laryngopharyngeal reflux is superior to that in classic gastroesophageal reflux disease. AB - Laryngopharyngeal reflux (LPR) in otolaryngology patients appears to be different from classic gastroesophageal reflux disease (GERD). In particular, esophagitis and its principal symptom, heartburn, considered the diagnostic sine qua non of GERD, are often absent in LPR. It has therefore been postulated that LPR patients have superior esophageal function. Esophageal acid clearance (EAC) is a measure of the ability of the esophagus to restore neutral pH after reflux events have occurred. It is considered an excellent overall measure of esophageal function. The mean EAC can be calculated from 24-hour pH monitoring data. A comparison of EAC in patients with GERD and LPR has not been previously reported. To compare the EAC of 1) patients with LPR alone, 2) patients with GERD alone, 3) patients with both LPR and GERD, and 4) patients without either LPR or GERD, we studied 200 otolaryngological patients who had undergone 24-hour double-probe (simultaneous pharyngeal and distal esophageal) pH monitoring, 50 in each group. The subgrouping of each patient was determined by previously established pH monitoring criteria. We defined GERD as abnormal esophageal reflux and LPR as abnormal pharyngeal reflux. The patients with GERD had a mean (+/-SD) EAC of 1.44 +/- 1.2 minutes, and those with LPR had a mean EAC of 1.00 +/- 1.00 minutes (p < .05). The patients with both GERD and LPR had a mean EAC of 1.53 +/- 1.01 minutes. The patients without reflux had a mean EAC of 0.53 +/- 0.38 minutes. We conclude that patients with LPR have significantly better EAC than those with GERD. These data suggest that patients with LPR have superior esophageal function. This finding may clarify our understanding of the differences in mechanisms, symptoms, and incidence of esophagitis in patients with LPR and GERD. PMID- 11768700 TI - Effects of gum chewing on pharyngeal and esophageal pH. AB - We investigated the effects of gum chewing on pharyngeal and esophageal pH levels in patients with laryngopharyngeal reflux (LPR) who were undergoing reflux testing. Forty consecutive, unselected, adult patients who were undergoing ambulatory double-probe (simultaneous pharyngeal and esophageal) pH monitoring for diagnosis of LPR were asked to chew 2 sticks of gum 4 times during their pH studies. Twenty subjects chewed regular sugarless gum, and 20 subjects chewed a sugarless gum containing bicarbonate. The subjects recorded the beginning and end of each gum-chewing period. The mean pH values for the gum-chewing intervals and for comparable pre-gum-chewing intervals were analyzed statistically for both the pharyngeal and esophageal probe data. The regular gum group and the bicarbonate gum group were analyzed separately. In addition, the gum-chewing pH data were compared to controls, ie, normal postcibal buffering effects. The data show that gum chewing consistently increases esophageal and pharyngeal pH, and that bicarbonate gum causes greater increases than regular gum. For patients with LPR, gum chewing appears to be a useful adjunctive antireflux therapy. PMID- 11768701 TI - Comparison of the phonation-related structures among pig, dog, white-tailed deer, and human larynges. AB - There is an important need for good animal models of the larynx for the study of the physiology of phonation. The dog's larynx has been used as an animal model for more than 2 centuries of phonatory research. However, there is some evidence that the pig larynx has advantages over the dog larynx as a model of phonation. Another larynx that is readily available is the deer larynx. In this comparative study, the laryngeal anatomy and function were examined in 4 species--human, pig, dog, and white-tailed deer. Particular attention was directed to those structures that one would predict could affect phonation, from the anatomic and biomechanical point of view. Although the vocal fold length was similar for all 4 species, the larynges described differed in some phonation-related characteristics. The data suggest that from a structural perspective, the pig larynx is a superior model for phonatory research. PMID- 11768702 TI - Superselective embolization as palliative treatment of recurrent hemorrhage in advanced carcinoma of the head and neck. AB - We report a case of recurrent major hemorrhage in a patient with advanced head and neck squamous cell carcinoma. Before and between the bleeding episodes, the functional level of the patient was remarkably high. Therefore, an attempt at bleeding control with superselective embolization with Ethibloc was made. Because of its specific characteristics, this substance is almost ideal for the purpose of palliative embolization. The material used and the technique of application are described in detail. After the procedure, no hemorrhage occurred for more than 4 months. We recommend superselective embolization, preferably with Ethibloc, for minimally invasive control of recurrent bleeding as palliative treatment in selected patients with advanced head and neck carcinoma, since significant benefit in terms of the quality of life may result. PMID- 11768703 TI - Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expressions and their differential regulation by proinflammatory cytokines and prostaglandin in nasal polyp fibroblasts. AB - Chronic inflammation of the paranasal sinus leads to nasal polyp (NP) formation. In this study, we investigated the effect of stimulation of the proinflammatory cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF alpha) and prostaglandin (PG) E2 on the production of messenger RNA (mRNA) of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-I (TIMP-1) in nasal polyp fibroblasts (NPFs) and nasal mucosa fibroblasts (NFs). The mRNAs of IL-1alpha, TNF-alpha, MMP-1, and TIMP-1 in 40 surgical specimens of NPs were studied by in situ hybridization to corroborate the in vitro findings. The results indicated a significant amount of constitutive MMP-1 mRNA in NPFs and cytokine-induced MMP-1 steady-state mRNAs in NFs. The effect of stimulation of cytokines on TIMP-1 mRNA synthesis was unremarkable in NPFs and NFs. Exogenous PGE2 enhanced cytokine-stimulated MMP-1 mRNA synthesis in NPFs. In situ hybridization revealed that cells expressing MMP-1 and TIMP-1 mRNAs (primarily plasma cells, fibroblasts, and endothelial cells) gathered around areas with loose stroma, suggestive of rapid extracellular matrix degradation. These data suggest that the pathogenesis of nasal polyposis could be related to production of MMP-1 and consequent promotion of matrix collagenolysis. PMID- 11768704 TI - Nontraumatic atlantoaxial rotary subluxation in the pediatric otolaryngology patient. A report of four cases. AB - Nontraumatic atlantoaxial rotary subluxation (NAARS) is a relatively uncommon entity, with inconsistent presentations. It most commonly follows infectious processes or operative procedures. We present our experience with 4 pediatric otolaryngology patients with NAARS who were treated at the University of Iowa Hospitals and Clinics during a 2-year period beginning in 1997. A review of the symptoms, physical findings, and radiographic abnormalities is presented. Treatment options, varying from muscle relaxants to surgical fusion, are discussed. A high index of suspicion in evaluating children with a stiff neck or pain on attempted motion is essential in order to facilitate prompt diagnosis and appropriate intervention. PMID- 11768705 TI - Eustachian tube function in children after insertion of ventilation tubes. AB - This study was performed to assess the effect of the insertion of ventilation tubes and the subsequent aeration of the middle ear on eustachian tube (ET) function in children. Manometric ET function tests were performed repeatedly for 3 months after the placement of ventilation tubes in 83 children with otitis media with effusion (OME). Opening and closing pressures (passive tubal function) and active tubal function were measured. Analysis of the results showed a significant increase in opening pressure over time, whereas the closing pressure did not change. The active tubal function did not change and remained at the same poor level. Therefore, the opening pressure and closing pressure and, especially, the poor active tubal function, were more likely to be a causal factor of OME than a result. Certain children may have poor intrinsic ET function that makes them more susceptible to OME. PMID- 11768706 TI - Morphometric analysis of age-related changes in the human basilar membrane. AB - The histopathologic correlates of presbycusis suggest several categories, including degeneration of sensory cells, neurons, or the stria vascularis. Lack of clear-cut histopathologic changes in some cases has suggested an "indeterminate category"; however, several studies have suggested that a disorder of the basilar membrane (BM) may underlie indeterminate presbycusis. The objective of the present study was to quantify age-related changes in the human BM and correlate them with audiometric patterns. Under high-resolution light microscopy, BM thickness was calculated, and the number of tympanic mesothelial cells (TMCs) lining the BM was counted, at 4 cochlear locations in 92 temporal bones. The control group (n = 80) included subjects from 10 decades of age with normal hearing and/or histopathologic findings. The indeterminate group (n = 12) consisted of elderly patients (ages 64 to 91 years) with hearing loss and no apparent histopathologic changes. Age-related BM thickening was seen in both groups, but only in the most basal cochlear region. The BM thickness in the indeterminate group was not significantly different from that of age-matched controls. Counts of TMCs showed age-related decreases in all cochlear regions in both groups; however, TMC counts in the indeterminate group were not different from those of age-matched controls. The results suggest that BM histopathology is not a common cause of presbycusis. Although age-related BM thickening, seen in both groups, could contribute to hearing loss, the extreme basal region, to which the thickening was confined, is not tested in routine audiometry. PMID- 11768707 TI - Geometric characterization of the laryngeal cartilage framework for the purpose of biomechanical modeling. AB - Some new anatomic data on the laryngeal cartilage framework have been obtained for the biomechanical modeling of the larynx. This study attempted to define and measure some biomechanically important morphometric features of the laryngeal framework, including both the human and the canine laryngeal frameworks, because the canine larynx has been frequently used as an animal model in gross morphology and in physiological experiments. The larynges of 9 men, 7 women, and 9 dogs were harvested and dissected after death. Linear and angular geometric measurements on the thyroid cartilage, the cricoid cartilage, and the arytenoid cartilage were made with a digital caliper and a protractor, respectively. The results are useful for constructing quantitative biomechanical models of vocal fold vibration and posturing (abduction and adduction), eg, continuum mechanical models and finite-element models of the vocal folds. PMID- 11768708 TI - Treatment of postparotidectomy salivary fistula with botulinum toxin. AB - We report on the successful treatment with botulinum toxin type A local injections of a salivary fistula that occurred after superficial parotidectomy. In a 58-year-old woman, transcutaneous discharge of saliva in the preauricular region had persisted in spite of 2 surgical revisions. Moreover, facial weakness and synkinesis had developed as a result of an iatrogenic lesion that had occurred at the time of primary surgery and required immediate reanastomosis of the main nerve trunk. Botulinum toxin A was injected into the deep lobe of the remaining parotid gland under ultrasonographic guidance. Additionally, botulinum toxin A was injected into the left orbicularis oculi muscle in order to improve the synkinesis. No adverse effects were observed. The sialorrhea was stopped for 11 months, and the synkinesis of the facial muscles was reduced significantly for 4 months. We conclude that botulinum toxin A injection is a successful alternative for the treatment of chronic salivary fistula. PMID- 11768709 TI - Management of a displaced endobronchial stent using simultaneous endoscopy and tracheobronchography. PMID- 11768710 TI - Stock optimizing in choice when a token deposit is the operant. AB - Each of 2 monkeys typically earned their daily food ration by depositing tokens in one of two slots. Tokens deposited in one slot dropped into a bin where they were kept (token kept). Deposits to a second slot dropped into a bin where they could be obtained again (token returned). In Experiment 1, a fixed-ratio (FR) 5 schedule that provided two food pellets was associated with each slot. Both monkeys preferred the token-returned slot. In Experiment 2, both subjects chose between unequal FR schedules with the token-returned slot always associated with the leaner schedule. When the FRs were 2 versus 3 and 2 versus 6, preferences were maintained for the token-returned slot; however, when the ratios were 2 versus 12, preference shifted to the token-kept slot. In Experiment 3, both monkeys chose between equal-valued concurrent variable-interval variable-interval schedules. Both monkeys preferred the slot that returned tokens. In Experiment 4, both monkeys chose between FRs that typically differed in size by a factor of 10. Both monkeys preferred the FR schedule that provided more food per trial. These data show that monkeys will choose so as to increase the number of reinforcers earned (stock optimizing) even when this preference reduces the rate of reinforcement (all reinforcers divided by session time). PMID- 11768711 TI - Speed contingencies, number of stimulus presentations, and the nodality effect in equivalence class formation. AB - Two experiments compared performances on conditional discrimination tasks using single-participant designs with and without speed contingencies. Experiment 1 was a systematic replication of Spencer and Chase (1996). Experiment 2 presented equal numbers of training and testing trials. In each experiment, 2 female undergraduates participated. Each formed three five-member and three seven-member equivalence classes in Experiments 1 and 2, respectively. Response speed was an inverse function of nodal number and relational type in Experiment 1, but only of relational type (i.e., baseline, symmetry, transitivity, and equivalence) in Experiment 2, with and without the speed contingency. Accuracy tended to peak without the speed contingency in both experiments. Adding the speed contingency increased response speeds in both experiments, more so in Experiment 2 with a lower limited hold for I participant. The results of Experiment 2 cast doubt on previous reports of the nodality effect and on the notion of "relatedness" among class members, and they support a reinforcement-contingency, rather than a structural, account of equivalence class formation. PMID- 11768712 TI - Habituation contributes to within-session changes in free wheel running. AB - Three experiments tested the hypothesis that habituation contributes to the regulation of wheel running. Rats ran in a wheel for 30-min sessions. Experiment 1 demonstrated spontaneous recovery. Rats ran more and the within-session decreases in running were smaller after 2 days of wheel deprivation than after 1 day. Experiment 2 demonstrated dishabituation. Running rate increased immediately after the termination of a brief extra event (application of the brake or flashing of the houselight). Experiment 3 demonstrated stimulus specificity. Rats completed the second half of the session in either the same wheel as the first half, or a different wheel. Second-half running was faster in the latter case. Within-session patterns of running were well described by equations that describe data from the habituation, motivation, and operant literatures. These results suggest that habituation contributes to the regulation of running. In fact, habituation provides a better explanation for the termination of wheel running than fatigue, the variable to which this termination is usually attributed. Overall, the present findings are consistent with the proposition that habituation and sensitization contribute to the regulation of several forms of motivated behavior. PMID- 11768713 TI - The development of functional response units: the role of demarcating stimuli. AB - An experiment with rats examined the roles of demarcating stimuli and differential reinforcement probability on the development of functional response units. It examined the development of units in a probabilistic, free-operant situation in which the presence of demarcating stimuli was manipulated. In all conditions, behavior became organized into two-response sequences framed by changes in local reinforcement probability. A tone demarcating the beginning and end of contingent response sequences facilitated the development of functional response units, as in chunking, but the same units developed slowly in the absence of the tone. Complex functional response units developed even though reinforcement contigencies remained constant. These findings demonstrate that models of operant learning must include a mechanism for changing the response unit as a function of reinforcement history. Markov models may seem to be a natural technique for modeling response sequences because of their ability to predict individual responses as a function of reinforcement history; however, no class of Markov chain can incorporate changing response units in their predictions. PMID- 11768714 TI - Determinants of reinforcer accumulation during an operant task. AB - Responses by rats on an earn lever made available food pellets that were delivered to a food cup by responses on a second, collect, lever. The rats could either collect and immediately consume or accumulate (defined as the percentage of multiple earn responses and as the number of pellets earned before a collect response) earned pellets. In Experiment 1, accumulation varied as a function of variations in the earn or collect response requirements and whether the earn and collect levers were proximal (31 cm) or distal (248 cm) to one another. Some accumulation occurred under all but one of the conditions, but generally was higher when the earn and collect levers were distal to one another, particularly when the earn response requirement was fixed-ratio (FR) 1. In Experiment 2, the contributions of responses and time to accumulation were assessed by comparing an FR 20 earn response requirement to a condition in which only a single earn response was required at the end of a time interval nominally yoked to the FR interval. When 248 cm separated the earn and collect levers, accumulation was always greater in the FR condition, and it was not systematically related to reinforcement rate. In Experiment 3, increasing the earn response requirement with a progressive-ratio schedule that reset only with a collect response increased the likelihood of accumulation when the collect and earn levers were 248 cm apart, even though such accumulation increased the next earn response requirement. Reinforcer accumulation is an understudied dimension of operant behavior that relates to the analysis of such phenomena as hoarding and self control, in that they too involve accumulating versus immediately collecting or consuming reinforcers. PMID- 11768715 TI - A precursor to the relational evaluation procedure: searching for the contextual cues that control equivalence responding. AB - The precursor to the relational evaluation procedure (pREP) is a go/no-go successive discrimination procedure for examining stimulus equivalence. Previous research has shown that it does not readily produce equivalence responding unless some matching-to-sample (MTS) procedures are incorporated into the experimental sequence. Two experiments attempted to identify contextual cues that would generate equivalence responding on the pREP. Experiment 1 examined the effects of using abstract symbols or various verbal labels as response options on the pREP. Only the words same and different, when used as response options, reliably produced equivalence responding across 4 subjects. Experiment 2 examined different pretraining preparations designed to attach the functions of the words same and different to abstract symbols that could then be used as response options on the pREP. The most effective pretraining procedure involved multiple exemplar training during which subjects were trained to respond to abstract symbols in the presence of pairs of stimuli that were either formally the same or different. The abstract symbols were subsequently used as response options with the pREP, and all subjects reliably demonstrated equivalence responding. The findings suggest that the relations of same and different may be fundamental to equivalence responding. These findings are discussed in terms of what they suggest about the nature of the equivalence phenomenon specifically and derived relational responding more generally. PMID- 11768716 TI - Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro. AB - Lung fibroblasts are activated to proliferate and produce connective tissue during the development of lung fibrosis. The 129 mouse strain does not develop asbestos-induced fibrogenesis, whereas several other inbred strains rapidly respond to inhaled fibers. Thus, in the experiments presented here, we have compared the responses of primary lung fibroblasts isolated from 129 and C57BL/6 mice. The 129 and C57BL/6 mouse lung fibroblasts (MLFs) proliferated similarly in 10% fetal bovine serum (FBS), but after quiescence, the 129 MLFs grew more slowly in serum and responded less to the BB isoform of platelet-derived growth factor. This is consistent with our finding that the mRNA for the PDGF-a receptor exhibits reduced expression by the 129 MLFs compared to those from C57BL/6 mice. Fibroblasts from the SJL mouse strain, from a C57BL/6-129 hybrid, and from the 3T3 cell line all proliferated more vigorously than MLFs from the 129 mice. In addition, the 129 MLFs exhibited reduced expression of alpha1 procollagen mRNA consequent to treatment with tumor necrosisfactor alpha. Based on these new findings, we suggest that the reduced fibrogenesis in asbestos-exposed 129 mice is due to an intrinsic difference in the ability of the lung fibroblasts to respond to peptide growth factors. PMID- 11768717 TI - PDGF-BB regulates IGF-mediated IGFBP-4 proteolysis in fetal lung fibroblasts. AB - Insulin-like growth factor (IGF)-stimulated lung fibroblast proliferation may be regulated by locally produced IGF-binding proteins (IGFBPs) during lung development. Recent evidence has shown that many growth factors participate in the regulation of cell proliferation by regulating IGFBPs. Because platelet derived growth factor-BB (PDGF-BB) is highly expressed during lung development and is known to regulate IGFBP-4 production by lung cells, we examined the mechanisms by which PDGF-BB regulates ICFBP-4 production using primary cultures of 19-day gestation rat lung fibroblasts. Exposure of fetal rat lung fibroblasts to PDGF-BB increased IGFBP-4 mRNA transcript abundance by 3.6- and 2.4-fold at 18 and 40 hours, respectively. Addition of Rp-adenosine-3'-5'-cyclic monophosphothioate triethylamine (rp-cAMPS), a competitive inhibitor of protein kinase A, blunted the PDGF-BB-stimulated increase in conditioned medium (CM) IGFBP-4 and the increase in IGFBP-4 mRNA. Proteolysis of IGFBP-4 was detected in aliquots of cell-free CM from cells exposed to SFM for 48 hours. IGFBP-4 proteolysis was inhibited by EDTA and 1,10-phenanthroline and was accentuated by the addition of IGF-I and IGF-II and, to a lesser extent, by des(1-3)IGF-I. Exposure of cells to PDGF-BB for 48 hours resulted in an inhibition of IGFBP-4 proteolysis that was associated with a decrease in the concentration of IGF-I in CM. These studies demonstrate that PDGF-BB increases the accumulation of ICFBP-4 in fetal rat lung fibroblasts CM through increased production and by inhibiting IGF-mediated IGFBP-4 proteolysis. PMID- 11768718 TI - Production of hepatocyte growth factor from human lung microvascular endothelial cells induced by interleukin-1beta. AB - To investigate the possible role of hepatocyte growth factor (HGF) in the reconstruction process following inflammatory damage in lung tissue, we compared HGF production of human lung microvascular endothelial cells (HLWECs) and human umbilical vein endothelial cells (HUVECs) after stimulation by interleukin(IL) 1beta. In an HLMEC-conditioned medium, large amounts of total (single and 2 chain) HGF were detected, and were 26- to 28-fold higher than those in HUVECs or human lung fibroblasts. The production of total HGF increased in a dose-dependent manner (4.7 to 9.2 times) with IL-1beta. In contrast, the amount of HGF in an HUVEC-conditioned medium was unaffected by IL-1beta treatment. The amount of cell associated HGF also showed a dose-related increase (140% to 160%) in HLMECs, but not in HUVECs with IL1beta. In addition, HGF and c-met (HGF receptor) mRNAs in HLMECs and HUVECs were examined by the RT-PCR method. HGF and c-met mRNAs were clearly detected in HLMECs before and after treatment with IL-1beta, but not in HUVECs. These results suggest that increases in HGF production from HLMECs may play a role in the reconstruction process following inflammatory damage in lung tissue. PMID- 11768719 TI - Differential regulation of calcitonin secretion in normal and neoplastic pulmonary neuroendocrine cells in vitro. AB - Within the mammalian lung, cells with a neuroendocrine phenotype are few in number and are sparsely distributed. In contrast, neuroendocrine neoplasms represent a major group of lung cancers. The aim of this study was to develop a model of mammalian PNECs and to compare glucocorticoid regulation of calcitonin secretion in normal and neoplastic cells with neuroendocrine differentiation. Cell cultures of PNECs were initiated after the disaggregation of neonatal hamster lungs with 0.1% collagenase and fractionation of the resultant cell suspension on a gradient of iodixanol (1.320 g/mL). Cell fractions enriched in PNECs were identified by positive staining for 5-hydroxytryptamine and the presence of calcitonin. Calcitonin secretion was investigated after exposure to hydrocortisone (0 to 1,000 nM). A dose-dependant inhibition of calcitonin secretion was seen after 7 days between 10 nM (55% of control), and 1,000 nM (29%) hydrocortisone. Cell cultures grown in the presence of hydrocortisone also contained significantly fewer PNECs between 10 nM (90% of control), and 1,000 nM (45%). Human bronchial carcinoid cells (NCIH727) cultured under identical conditions showed a similar inhibition of calcitonin secretion between 10 nM (53%) and 1,000 nM (52%), although at these concentrations, no reduction in cell number was seen. In contrast, 2 human small cell lung cancer cell lines (DMS-79 and COR-L24 cells) showed no dose-dependent inhibition of calcitonin secretion and no effect on cell proliferation in response to hydrocortisone. These results show that enriched cultures of mammalian PNECs can be used to investigate functional aspects of their biology, including peptide secretion in response to potential regulators. Furthermore, calcitonin secretion is inhibited in normal PNECs and bronchial carcinoid cells at physiological concentrations of glucocorticoids, but this feature appears not to be present in the 2 more invasive neuroendocrine neoplasms (small cell lung cancer cells) investigated in this study. PMID- 11768720 TI - Guidelines for the management of hypertension for general practitioners. PMID- 11768721 TI - An association study of five genetic loci and left ventricular hypertrophy amongst Gulf Arabs. AB - We carried out an association (case-control) study of five candidate genes--G protein beta3 subunit gene variant; methylene tetrahydrofolate reductase (MTHFR); angiotensin converting enzyme (ACE) gene; and paraoxonase 1 and 2 (PON 1 and 2) genes--in a United Arab Emirati population. The aim was to establish a possible relationship between these five candidate genes and clinical left ventricular hypertrophy (LVH) in a genetically homogenous group. DNA samples were collected from 213 unrelated Nationals who were further segregated into 98 subjects with LVH (78 hypertensives and 20 normotensives) and 115 (23 hypertensives and 92 normotensives) age- and sex-matched controls who did not present with LVH. Of the five candidate gene markers studied, no significant differences in the genotype distribution of the MTHFR, PON 1 and 2 or ACE markers were found between the LVH and non-LVH groups. However, a possible association was found between the beta3 G protein C825T marker and LVH. In conclusion, our results suggest an association between LVH and the C825T allele of the G-protein beta3 subunit gene. PMID- 11768722 TI - Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. AB - The object of this study is to evaluate the long-term effects of olmesartan on hypertension and the renin-angiotensin-aldosterone system in hypertensive patients. This study evaluated 26 hypertensive male and female outpatients, 38-69 years of age, with a systolic blood pressure > or = 160 mmHg and/or a diastolic blood pressure > or = 95 mmHg. Oral doses of 5 to 40 mg olmesartan were administered once daily. Blood pressure and renin-angiotensin-aldosterone parameters (plasma renin activity and plasma angiotensin I, II, and aldosterone concentrations) were evaluated at 12-16 weeks, 6 months, and 1 year after the start of olmesartan administration. Systolic and diastolic blood pressures were significantly decreased following the administration of olmesartan. The observed decreases in systolic and diastolic blood pressures after 1 year of treatment were 28.8+/-2.1 mmHg and 15.8+/-1.3 mmHg, respectively. No change was observed in the pulse rate. The plasma renin activity increased significantly from a baseline premedication mean of 1.26+/-0.31 ng/ml/h to a mean of 2.58+/-0.74 ng/ml/h and 2.87+/-0.72 ng/ml/h after 6 months and 1 year of treatment, respectively. Angiotensin II levels decreased significantly from a baseline of 20.4+/-3.2 pg/ml to a mean of 8.6+/-2.1 pg/ml and 6.8+/-1.8 pg/ml after 6 months and 1 year of treatment, respectively. The plasma aldosterone level also decreased significantly after 6 months of treatment. In hypertensive patients, the long term administration of olmesartan, a novel AT1 receptor antagonist, decreased both blood pressure and plasma angiotensin II levels. PMID- 11768723 TI - Effects of a community-based lifestyle-modification program on cardiovascular risk factors in middle-aged women. AB - We investigate the effectiveness of a community-based lifestyle-modification program for reducing blood pressure and other cardiovascular risk factors in sedentary Japanese middle-aged women. Among an initial cohort of 210 middle-aged sedentary women, 195 subjects completed a community-based 12-week lifestyle modification program for reducing cardiovascular risk factors. Blood pressure, body weight and the serum lipid profile were measured both at baseline and at the end of the 12-week lifestyle-modification program. The program consisted of mild aerobic exercise and a mild hypocaloric diet. After the 12-week program, both systolic and diastolic blood pressure were significantly reduced, especially in subjects who were hypertensive at baseline. Desirable changes in body weight and the serum lipid profile were also found after the 12-week program. Multiple linear regression analysis revealed that, in obese subjects, the decrease in systolic blood pressure was correlated with both the initial systolic blood pressure and the change in estimated maximum oxygen consumption. In addition, the decrease in diastolic blood pressure was correlated with the initial diastolic blood pressure and the change in body weight. On the other hand, in non-obese subjects, the decrease in blood pressure was correlated with the initial blood pressure and the change in salt intake. A community-based lifestyle-modification program that consisted of mild aerobic exercise and a mild hypocaloric diet was considered to be practically effective for reducing multiple cardiovascular risk factors. Individuals who already have one or more mild cardiovascular risk factors still could be good candidates for a community-based lifestyle modification program. PMID- 11768724 TI - Altered diurnal variation of blood pressure in elderly subjects with decreased activity of daily living and impaired cognitive function. AB - Activity of daily living (ADL) and cognitive are indices of physical and psychological activity in elderly subjects. The present study was performed to clarify the relationship among ADL, cognitive function, and ambulatory blood pressure (ABP) in the elderly. Study subjects were 77 females and 22 males (aged 60 to 101 years) with various levels of ADL and cognition, who were in nursing homes or geriatric hospitals. ABP was recorded every 30 min for 24 h by a noninvasive device. Mini-mental state examination (MMSE) and Barthel index measurement were used to evaluate cognitive function and ADL, respectively. Both the MMSE and Barthel index values showed a significant positive correlation with daytime ABP but not with nighttime ABP. The dip in nighttime BP correlated negatively with age, and positively with MMSE and Barthel index. In the multiple regression analysis, age and Barthel index values remained significant determinants of the dip in nighttime BP. Presence of stroke and MMSE became significant when the Barthel index values were removed from the analyses. When subjects were classified by tertiles of MMSE or Barthel index, subjects in the lowest MMSE group and those in the lowest Barthel index group had both lower daytime ABP and smaller nighttime BP dip than those of the other groups. A low BP level during the daytime was associated with altered diurnal variation of BP in elderly subjects with greater age, impaired cognitive function, and/or decreased ADL. ADL had a greater influence on diurnal BP variation than did cognitive function. PMID- 11768725 TI - Associations of plasma endothelin concentration with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension. AB - We studied the association of endothelin (ET)-1 with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension. Neurologically normal patients with essential hypertension (n=293; 138 male, 155 female; mean age, 65 years) and age-matched control subjects (n=242) were studied with B-mode ultrasonography of the common and internal carotid arteries and magnetic resonance imaging of the brain. Plasma ET-1 was measured by enzyme immunoassay. Hypertensive patients were divided into groups with carotid plaques and low ET-1 concentrations (< 0.75 pg/ml; PL group); carotid plaques and mid range ET-1 (0.75 to 1.55 pg/ml; PM group); carotid plaques and high ET-1 (> or = 1.55 pg/ml; PH group); no plaques and low ET-1 (NPL); no plaques and mid-range ET 1 (NPM); and no plaques and high ET-1 (NPH). Overall, ET-1 concentrations were significantly higher in patients than in control subjects. Carotid plaque prevalence was significantly related to ET-1 in hypertensive patients. ET-1 showed a significant positive relationship with the number of asymptomatic lacunar infarcts of the brain in hypertensive patients with carotid plaques (rho=0.48, p<0.001). No significant relationship was seen between ET-1 and periventricular hyperintensity scores in patients with plaques. ET-1 did not show a relationship to either brain lesion type in patients without carotid plaques. Thus, ET-1 may foster asymptomatic lacunar cerebral infarcts by promoting carotid atherosclerosis in patients with essential hypertension. PMID- 11768726 TI - Effects of antihypertensive agents on blood pressure during exercise. AB - The relationship between blood pressure (BP) and cardiovascular morbidity has been appreciated for many years. Casual BP may not be representative of the pressure at other times. It is recognized that BP during exercise may be a more accurate predictor than casual BP. There is, however, little information about the effects of antihypertensive drugs on the BP during exercise. This study was designed to investigate the effects of various antihypertensive agents on BP during exercise. Sixty-four patients (age, 49+/-10 years) with untreated essential hypertension (WHO I, II) were studied during a supine ergometric exercise regimen. A graded exercise test was started at a workload of 50 W, and the load was increased by 25 W every 3 min. The hemodynamic responses to exercise were evaluated by changes in systolic and diastolic BP (SBP, DBP) and heart rate (HR). Plasma norepinephrine (NE) levels were measured at rest and during submaximal exercise, and before and after 4 weeks of treatment with metoprolol (METO), doxazosin (DOXA), trichlormethiazide (TCTZ), nifedipine (NIFE), amlodipine (AMLO) and temocapril (TEMO) between left ventricular mass index (LVMI) and BP values at rest, during exercise, and during the recovery period after exercise were assessed by multiple regression analysis. The stepwise selection (forward conditional) method showed that LVMI was significantly associated with SBP during submaximal exercise and during the recovery period. All antihypertensive treatments decreased SBP and DBP (p<0.01) at rest. METO, AMLO and TEMO significantly lowered SBP (p<0.05) during exercise, whereas DOXA, TCTZ and NIFE induced no change in SBP. The exercise-induced increase of plasma NE was further enhanced by METO and NIFE but not by AMLO, DOXA, or TCTZ, and it was significantly suppressed by TEMO (p<0.01). These results suggest that BP during exercise is more highly associated with the progression of left ventricular hypertrophy (LVH) than is casual BP. Because antihypertensive agents differ in their effects on exercise hemodynamics, we recommend that hemodynamic factors during exercise be considered when selecting the optimal antihypertensive medication for highly active patients. PMID- 11768727 TI - Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine. AB - The clinical significance of N-type calcium channel blockade has not been fully examined. We here compared the effects of the N-type calcium channel blockers cilnidipine and amlodipine on the sympathetic nervous system and platelet function in hypertension under resting and stressed conditions. Thirty-two patients with hypertension (58+/-9 years) received cilnidipine or amlodipine for 4 weeks in this crossover study. On day 28 of each treatment, plasma levels of epinephrine (EP), norepinephrine (NEP), and beta-thromboglobulin (BTG), and EC50 of ADP-induced platelet aggregation (ADPE50) were determined at rest and after a cold pressor test. On day 29, the group receiving cilnidipine was switched to amlodipine treatment, and vice versa. At rest, the blood pressure, heart rates, EP, NEP, ADPEC50, and BTG, were similar in both treatments. After the cold pressor test, increases in EP (35+/-17 to 44+/-25 pg/ml; p<0.05) and BTG (40+/-13 to 49+/-22 ng/ml; p<0.01) and a decrease in ADPEC50 (32+/-26 to 27+/-24 micromol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment. In addition, the increase in NEP was significantly greater (p<0.05) in the amlodipine (276+/-78 to 318+/-87 pg/ml; p<0.01) than in the cilnidipine treatment (273+/-88 to 291+/-100 pg/ml; p<0.05). Cilnidipine more highly attenuates the activation of platelet function in response to cold pressor stress than does amlodipine. Attenuated activation of the sympathetic nervous system via N-type calcium channel blockade may contribute to this phenomenon. PMID- 11768728 TI - Application of the updated Framingham risk score to Japanese men. AB - Few tools for risk assessment of coronary heart disease (CHD) have yet been made available in Japan. This study aims to examine the validity of the updated Framingham risk score as applied to a Japanese male population. Using the annual health examination database of a Japanese company, we followed-up 5,611 male subjects, aged 30 to 59 years, who had initially recorded neither history of cardiovascular disease nor electrocardiographical ischemic changes, in order to observe the occurrence of CHD over a period of 5 to 7 years. The total score calculated by the Framingham risk score sheet (the Framingham point score) was used as an indicator of CHD risk for the subject individually. The mean of the Framingham point score for 80 CHD cases was significantly higher than that for 5,531 non-CHD cases. The incidence of CHD gradually increased with the Framingham point score. In the receiver operating characteristic analysis, the area under the curve reached 0.71. At 6 points, the curve came closest to the upper left hand corner, with a specificity of 0.74 and sensitivity of 0.59. On the other hand, multivariable-adjusted relative risks associated with old age, high blood pressure, low HDL cholesterol and smoking in the Japanese male population were different from those in the Framingham population. Despite the low incidence of CHD, the updated Framingham risk score could provide a reasonable rank ordering of CHD risk and could identify Japanese men (and possible other individuals) at high risk for CHD with considerable accuracy. However, further study of Japanese populations may be required to reappraise several coefficients of risk factor in the risk scoring model. PMID- 11768729 TI - Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. AB - A high level of serum creatinine (S-Cr) is a predictor of end-stage renal disease (ESRD), but only a few studies have investigated the prevalence of high S-Cr and its correlates in a large population. We analyzed the data collected from 6,403 subjects (4,222 men and 2,181 women) who participated in the Okinawa General Health Maintenance Association (OGHMA) screening both at 1997 and 1999. The computer-saved data included sex, age, blood chemistries, blood pressure, medical histories, and lifestyles. Multivariate Cox proportional hazard analyses were performed to identify the correlates of developing high S-Cr levels: > or = 1.4 mg/dl in men and > or = 1.2 mg/dl in women. The prevalence of high S-Cr was 3.0% (N=193), which was 4.1% in men (N=175) and 0.8% in women (N=18), and increased with age in both sexes at the 1997 screening. Among those who showed normal levels of S-Cr in 1997 (N=6,210), 241 subjects (223 men and 18 women) developed high S-Cr. The 2-year cumulative incidence of high S-Cr was 5.5% in men and 0.8% in women. Other than sex, serum uric acid was the most significant correlate for developing high S-Cr. The adjusted relative risk (95% confidence interval) of those with serum uric acid 8.0 mg/dl and over was 2.91 (1.79-4.75) in men and 10.39 (1.91-56.62) in women when compared to those with serum uric acid less than 5.0 mg/dl. Prevalence of high levels of S-Cr was relatively high in men. Other than gender, serum uric acid was a significant positive correlate of developing high S-Cr in this sample of the Japanese population. PMID- 11768730 TI - Nitric oxide buffers renal medullary vasoconstriction induced by prostaglandins synthesis blockade. AB - The aim of this study was to examine whether nitric oxide (NO) buffers the renal medullary vasoconstriction induced by a prostaglandins (PG) synthesis inhibitor. Daily blood pressure measurements were made with implanted catheters and changes in cortical blood flow (CBF) and medullary blood flow (MBF) were determined by implanted optical fibers and laser-Doppler flow measurement techniques in conscious rats. Sodium and water balance were also determined. Infusion of meclofenamate, a nonisozyme-specific cyclooxygenase (COX) inhibitor, at 5 microg/kg/min over 4 consecutive days (n=12 rats) elicited a transitory increase (p<0.05) in mean arterial pressure (MAP) and a transitory decrease (p<0.05) in MBF and sodium excretion without altering CBF. In contrast, the simultaneous infusion of meclofenamate and N(G)-nitro-L-arginine methyl ester (L-NAME, 0.8 microg/kg/min), a NO synthesis inhibitor, over 4 consecutive days (n=12) produced a continuous increase (p<0.01) in MAP and a continuous decrease (p<0.05) in MBF and sodium excretion without altering CBF. The results of this study suggest that the renal medullary vasoconstrictor effects and sodium retention induced by meclofenamate are enhanced by a subpressor dose of L-NAME, and that NO may buffer the renal medullary vasoconstriction induced by the blockade of PG synthesis in conscious rats. PMID- 11768731 TI - Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors. AB - Targeted disruption of the klotho gene induces multiple phenotypes characteristic of human aging, including arteriosclerosis, pulmonary emphysema and osteoporosis. Moreover, we previously observed that insufficient klotho expression in mice leads to endothelial dysfunction. In the present study, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which exhibit hypertension, obesity, severe hyperglycemia and hypertriglyceridemia, and are thus considered an animal model of atherogenic disease, to test the effects of oral administration of troglitazone (200 mg/kg) on renal klotho mRNA expression and endothelial function. Systolic blood pressure, body weight, plasma glucose and triglyceride levels were all significantly higher in 30-week-old OLETF rats than in controls (LETO; Long-Evans Tokushima Otsuka) (p<0.05, n=7). In addition, endothelium dependent relaxation of the aorta in response to 10(-5) M acetylcholine was significantly attenuated in OLETF rats (p<0.05, n=7), as was renal expression of klotho mRNA. Administration of troglitazone for 10 weeks significantly reduced systolic blood pressure, plasma glucose and triglyceride levels in OLETF rats, while augmenting endothelium-dependent aortic relaxation and renal klotho mRNA expression. These findings suggest that troglitazone protects the vascular endothelium against damage caused by the presence of multiple atherogenic factors. PMID- 11768732 TI - Sodium chloride loading does not alter endothelium-dependent vasodilation of forearm vasculature in either salt-sensitive or salt-resistant patients with essential hypertension. AB - The purpose of this study was to determine whether a high NaCl intake impairs endothelium-dependent and -independent vasodilation of forearm circulation in salt sensitive (SS) patients with essential hypertension. We evaluated the effects of intra-arterial acetylcholine (ACh) and isosorbide dinitrate (ISDN) on forearm hemodynamics in 29 patients with essential hypertension, while consuming a low NaCl (50 mmol/d) or high Na Cl (340 mmol/d) diet for 1 week. The forearm blood flow (FBF) was measured by strain-gauge plethysmography. Patients were classified as SS (n=12) or salt resistant (SR; n=17) based on salt-induced changes in blood pressures. The FBF responses of ACh and ISDN were similar in the SS and SR patients while on either NaCl diet, and was not altered by salt loading (ACh, SS: low NaCl 22.8+/-4.3 vs. high NaCl 21.1+/-3.6 ml/min per 100 ml, SR: low NaCl 22.5+/-4.0 vs. high NaCl 23.3+/-4.1 ml/min per 100 ml; ISDN, SS: low NaCl 13.9+/-2.1 vs. high NaCl 14.1+/-2.2 ml/min per 100 ml, SR: low NaCl 13.8+/-2.3 vs. high NaCl 14.0+/-2.2 ml/min per 100 ml). There were no significant differences in the vascular responses to ACh and ISDN in the presence of N(G) monomethyl-L-arginine, a nitric oxide synthase inhibitor, in either group for either NaCl diet. These findings suggest that forearm resistance artery endothelial function may not be influenced by salt loading in either SS patients which finding may play a role in determining salt sensitivity in patients with essential hypertension or SR patients. PMID- 11768733 TI - Acute effect of human cardiotrophin-1 on hemodynamic parameters in spontaneously hypertensive rats and Wistar Kyoto rats. AB - There is considerable evidence to indicate that humoral factors play an important role in the development of left ventricular hypertrophy. Cardiotrophin-1 (CT-1) is a cytokine that has been shown to induce cardiac hypertrophy in a dose dependent manner. The aim of the present study was to investigate the acute effect of CT-1 on hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) and to study the relationship between the plasma concentration of CT-1 and its hemodynamic effect. Ten-week-old SHR and age matched WKY were used. Blood pressure (BP), heart rate (HR) and plasma concentration of CT-1 were measured both before and for 60 min after intravenous bolus injection of human CT-1 (10 microg/kg). CT-1 injection significantly decreased BP and significantly increased HR in SHR and WKY. There were significant differences in BP and HR between the two groups at all time points after injection. The lowest BP, highest HR and maximal plasma concentrations of CT-1 were observed in both groups within 10 min after injection. However, after converting the values into the percentage change from their respective baselines, there were no significant differences between the two groups in BP or HR at any time point. There was also no significant difference between the two groups at any time point in the plasma concentration of CT-1. This study indicates that CT 1 decreases BP and increases HR in both SHR and WKY. The most obvious change occurred within 10 min after injection. However, there was no significant difference in the hypotensive effect of CT-1 on 10-week-old SHR and WKY. PMID- 11768734 TI - Combined primary aldosteronism and preclinical Cushing's syndrome: an unusual case presentation of adrenal adenoma. AB - A 55-year-old woman was referred to our institution for evaluation of elevated plasma creatine phosphokinase, hypokalemia and hypertension. Her chief complaints were muscle weakness and polyuria. A left adrenal mass, 4 cm in diameter, was noted on computed tomography. Hormonal assessment demonstrated markedly elevated plasma aldosterone concentration, markedly low plasma renin activity, an abnormal diurnal variation in serum cortisol levels, suppressed baseline plasma adrenocorticotrophic hormone, and non-suppression of serum cortisol by dexamethasone suppression test. She showed no symptoms or signs suggestive of Cushing's syndrome. Adrenal scintigraphy with 131I-6-beta-iodomethyl norcholesterol showed uptake on the left adrenal and inhibition of the contralateral adrenal gland. She was diagnosed with combined primary aldosteronism and preclinical Cushing's syndrome. Cases of combined primary aldosteronism and preclinical Cushing's syndrome are extremely rare. In patients with large aldosterone-producing adenoma, contralateral adrenal insufficiency should be anticipated after the removal of the tumor. PMID- 11768735 TI - The change and significance of the Na+-K+-ATPase alpha-subunit in ouabain hypertensive rats. AB - Ouabain has recently been identified as an endogenous Na+-K+ pump inhibitor having a close association with hypertension. However, some patients with hypertention do not show high levels of endogenous ouabain (EO), and patients with high EO levels do not necessarily suffer from hypertention. It is believed that the Na+-K+-ATPase activity in essential hypertension does not undergo homogenous change. The present study was designed, therefore, to investigate the expression and the significance of the Na+-K+-ATPase alpha-subunit isoforms in kidney tissue in ouabain-hypertensive rats. Ouabain was administered chronically to establish a model of ouabain-hypertensive rats. Biochemical analysis, cytobiology and sABC immunohistochemistry were they used to assay for expression of Na+-K+-ATPase alpha-subunit isoforms in kidney tissue. After the first week of receiving ouabain, 65% (n=13) of rats had hypertension. After the second week, the blood pressure of these 13 hypertensive rats was increased significantly compared to the baseline and control levels (p<0.05). The plasma renin activity was normal, and angiotensin II and aldosterone levels were increased significantly in these rats (p<0.05). But in the other 35% (n=7) of rats of the experimental group, there was no apparent increase in blood pressure after receiving ouabain. The plasma ouabain level in the non-hypertensive subgroup was significantly higher than that in the hypertensive subgroup, but the 86Rb intake and the number of 3H-ouabain binding sites did not decrease. The Na+-K+-ATPase activity showed non-homogeneous changes. In hypertensive rats, the expression levels of ouabain paralleled the degree of hypertension (r=0.88, p<0.05). The positive granules were mainly scattered in the cytoblastoma of the reticular zone of adrenal cortex. There were thus different levels of expression of Na+-K+ ATPase alpha-subunit isoforms in this model. In the hypertension subgroup the alpha1 was most strongly expressed, followed by the alpha2 and alpha3 isforms. But in the non-hypertensive subgroup the order was alpha3 > alpha2 > alpha1. The positive granular was mainly scattered in the convoluted tubules of the kidney. These results suggest that the high level of ouabain and the change of the Na+-K+ ATPase alpha-subunit isoforms may play a critical role in hypertension. PMID- 11768736 TI - Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. AB - The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8 OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke. PMID- 11768737 TI - Clinical usefulness of electron beam computed tomography to detect coronary artery calcification. PMID- 11768738 TI - Carvedilol in the failing heart. AB - Patients with chronic heart failure due to left ventricular systolic dysfunction of ischemic or nonischemic etiology have shown improvement in morbidity and mortality with carvedilol therapy. In patients with symptomatic (New York Heart Association class II-IV) heart failure, carvedilol improves left ventricular ejection fraction and clinical status, and slows disease progression, reducing the combined risk of mortality and hospitalization. Despite the overwhelming evidence for their benefit, there continues to be a large treatment gap between those who would derive benefit and those who actually receive the drug. In this article, the pharmacology, clinical trial evidence, and the potential differences between carvedilol and other beta blockers are discussed. Carvedilol provides powerful therapy in the treatment of chronic heart failure caused by a variety of etiologies and in a wide array of clinical settings. PMID- 11768739 TI - Should functional cardiac murmurs be diagnosed by auscultation or by Doppler echocardiography? AB - BACKGROUND: For many years, cardiac auscultation has been the only available method for distinguishing between functional and organic murmurs; however, a more reliable differential diagnosis can now be achieved with Doppler echocardiography. The question remains as to whether a Doppler echocardiogram needs to be routinely recorded in the presence of a heart murmur or whether the auscultatory diagnosis of a functional murmur is sufficient. HYPOTHESIS: This prospective study attempts to answer this important question at a time when medical costs have to be curbed. METHODS: The three cardiologists involved in this study saw 516 new patients in their private practice over a 10-month period; of these, 321 (63.6%) underwent Doppler echocardiography. All patients underwent careful auscultation prior to echocardiography. At the end of their examinations, the cardiologists noted whether they considered the murmur to be of functional or organic origin. Minimal mitral or aortic regurgitations of short duration and low velocity occurring on non-thickened valves were considered functional. RESULTS: The results for cardiac auscultation and Doppler echocardiography were considered to be concordant, that is, both techniques diagnosed either a functional or organic murmur in 250 of 321 patients (77.9%). The results for cardiac auscultation and Doppler echocardiography showed a major discordance in just six cases (1.9%). All were mitral regurgitations of moderate severity. CONCLUSION: The prevalence of cardiac murmurs in the general population is very high. As echocardiography currently represents a significant proportion of cardiac medical expenditure, it would be wise to limit the use of this technique to essential indications. This study confirms that both cardiac auscultation and Doppler echocardiography possess important limitations. Nevertheless, it also shows that well-trained cardiologists can identify the vast majority of functional murmurs on auscultation. Better training of nonspecialist physicians in cardiac auscultation may help in containing medical expenses. PMID- 11768740 TI - Correlates of bundle-branch block in patients undergoing primary angioplasty for acute myocardial infarction. AB - BACKGROUND: Early reperfusion therapy has reduced the infarct size and mortality rate in patients with acute myocardial infarction (AMI). The occurrence of bundle branch block in AMI is related to the amount of myocardial damage and the insult to the conduction system. HYPOTHESIS: To evaluate the clinical and angiographic factors related to the occurrence of bundle-branch block (BBB) in patients with primary percutaneous transluminal coronary angioplasty (PTCA), we investigated consecutive series of patients with their first Q-wave AMI and successful PTCA. METHODS: Coronary angiogram at the time of admission, electrocardiogram, and echocardiogram were evaluated in 279 patients with their first Q-wave AMI and successful PTCA. RESULTS: Bundle-branch block was detected in 26 patients (9%); 16 patients had transient and 10 patients had persistent block, while 16 patients had bifascicular block and 10 patients had right BBB. The patients with BBB had a significantly larger number of left ventricular asynergic segments, higher incidence of total occlusion of infarct-related artery, angiographic no reflow, and pericardial rub than those without BBB. When the multivariate analysis was performed using five clinical markers of infarct severity, angiographic no reflow (F = 20.2, p < 0.001) and total occlusion of infarct-re-lated artery (F = 4.2, p = 0.04) were found to be the significant variables related to BBB. CONCLUSIONS: Despite successful primary PTCA, absence of antegrade flow in the infarct-related artery at the onset of AMI and/or angiographic no reflow resulted in more severe transmural myocardial damage and, hence, the occurrence of BBB. PMID- 11768741 TI - Right ventricular electrocardiographic leads for detection of Brugada syndrome in sudden unexplained death syndrome survivors and their relatives. AB - BACKGROUND: Sudden unexplained death syndrome (SUDS) is a sudden death syndrome in previously healthy Southeast Asian young adults without any structural causes of death. Many SUDS survivors show electrocardiographic (ECG) evidence of RSR' and ST elevation in leads V1 to V3, which is similar to the ECG pattern in Brugada syndrome. However, in many cases transient normalization of the ECG does not make diagnosis with standard 12-lead ECG possible. HYPOTHESIS: To overcome this problem, we utilized the new right ventricular ECG leads to detect the Brugada syndrome in SUDS survivors. METHODS: The subject was a Thai male patient who presented with a SUDS-like syncopal attack. He had cardiac arrest due to idiopathic ventricular fibrillation. RESULTS: Post-resuscitation standard 12-lead ECG showed no diagnostic features of Brugada syndrome. However, ECG patterns of RSR' and ST elevations typical for Brugada syndrome could be detected at the higher intercostal space leads V1 to V3. We observed similar findings in 2 of the other 10 SUDS survivors and 4 of 23 healthy family members. CONCLUSIONS: Our data suggest that these new right ventricular leads ECG may be helpful in detecting Brugada syndrome in SUDS survivors and their relatives. PMID- 11768742 TI - Inducible ventricular arrhythmias and patency of infarct-related artery in survivors of acute myocardial infarction. AB - BACKGROUND: Patency of infarct-related artery in patients who suffered an acute myocardial infarction (AMI) has been shown to be associated with improved survival. Ventricular tachyarrhythmias induced by programmed electrical stimulation may be predictive of arrhythmic events and sudden death. HYPOTHESIS: The study was undertaken to assess the possible effect of a patent infarct related coronary artery on induced ventricular tachyarrhythmias during programmed ventricular stimulation in survivors of AMI. METHODS: In this prospective study, programmed electrical stimulation was performed before hospital discharge (14 +/- 2 days) in 79 patients who survived an AMI. Patients were subdivided into two groups: Group I with patent infarct-related coronary artery (n = 64) and Group 2 with occluded infarct-related artery (n = 15) at coronary angiography performed at 14 +/- 2 days. These two groups were comparable in terms of mean left ventricular ejection fraction, location of infarct-related artery, number of diseased vessels, peak creatine kinase value, and infarct location. RESULTS: Ventricular arrhythmias were induced in 21 patients ( 32.6%) of Group I and 4 patients (26.6%) of Group 2. This difference was not statistically significant. CONCLUSION: This study suggests that ventricular arrhythmias induced by programmed ventricular stimulation in survivors of AMI did not differ whether the infarct-related artery was patent or occluded. Other factors may play a role in electrical instability as assessed by programmed ventricular stimulation. PMID- 11768743 TI - Digoxin withdrawal in patients with dilated cardiomyopathy following normalization of ejection fraction with beta blockers. AB - BACKGROUND: The effect of withdrawal of digoxin on left ventricular function in patients with a history of idiopathic dilated cardiomyopathy (IDCM) following normalization of left ventricular ejection fraction (LVEF) with beta blockers remains unknown. HYPOTHESIS: This study was undertaken to determine the effect of digoxin withdrawal on left ventricular function in patients with IDCM. METHODS: In 8 consecutive patients with IDCM (5 men, 3 women) who had normalization of LVEF following beta-blocker treatment, digoxin was withdrawn as part of an office protocol. and LVEF was followed. Baseline EF prior to beta blocker initiation (carvedilol = 6, atenolol = 1, metoprolol 1) was measured with isotope ventriculography (IVG), echocardiography, or left ventriculography. Post beta blocker ejection fraction (post BB EF) was measured in all patients with IVG at a mean of 17.25 +/- 5.38 months. Follow-up EF was measured using IVG after digoxin withdrawal at a mean of 6.99 +/- 4.34 months. RESULTS: An experienced blinded reader interpreted the IVG scans. Baseline EF was 28.5 +/- 8.26; post BB EF and follow-up EF were 56.1 +/- 4.65 and 51.0 +/- 7.35, respectively (p = 0.05). CONCLUSION: These data provide potential evidence that digoxin withdrawal can result in a small but significant reduction in LVEF in patients with IDCM who had normalization of LVEF after treatment with beta blockers. Mean LVEF, however, remained within normal (> 50%) on beta-blocker therapy and without digitalis. Large, randomized controlled trials are needed to confirm these findings. PMID- 11768744 TI - Acute thrombotic occlusion of the left main coronary artery in a hypercoagulable patient treated with intracoronary abciximab. PMID- 11768745 TI - Profiles in cardiology. Harriet P. Dustan. PMID- 11768746 TI - Clomipramine and related structures as inhibitors of the skeletal sarcoplasmic reticulum Ca2+ pump. AB - The Ca2+-pumping activity of skeletal sarcoplasmic reticulum vesicles is half maximally inhibited by 120 microM clomipramine, 250 microM desipramine, and 500 microM imipramine or trimipramine. The inhibition is attributed to the dihydrodibenzazepine moiety, since 3-(dimethylamino)propionitrile, reproducing the aliphatic amine chain, has no inhibitory action. The inhibition is shown as a marked decrease of Ca2+ binding at equilibrium in the absence of ATP and as a reduction of phosphorylation of the Ca2+-free conformation by inorganic phosphate. Therefore, the drug effect is consistent with preferential interaction of tricyclic antidepressants with the Ca2+-free conformation of the nonphosphorylated enzyme. An additional decrease in the apparent rate constant of enzyme dephosphorylation, i.e., in the release of phosphate from ATP during enzyme cycling was also noticed. PMID- 11768747 TI - Heme centers of Rhodothermus marinus respiratory chain. Characterization of its cbb3 oxidase. AB - Rhodothermus (R.) marinus, a thermohalophilic gram-negative, and strict aerobic bacterium, has a rather distinct respiratory chain, containing a caa3 terminal oxidase, a novel cytochrome bc complex and a HiPIP, which is an electron carrier between this complex and a terminal oxidase (Pereira et al (1999a, c). To further elucidate this unusual respiratory system, its membrane-bound heme centers were characterized by visible and EPR spectroscopies as well as by redox potentiometry. Rhodothermus marinus contains mostly B- and C-type hemes; a small amount of A-type heme is also detected. The heme centers have relatively low reduction potentials, ranging from ca. +250 to -60 mV, at pH 7. A Rieske-type center was not detected, suggesting the absence of a canonical complex III. The major terminal oxidase expressed by R. marinus is a cbb3-type oxidase. Its presence is in agreement with molecular biology studies, which reveal the existence of a gene encoding for a FixN-type oxidase. The oxidase was partially purified and appears to have five subunits, with apparent molecular masses of 64, 57, 36, 26 (C-type heme subunit), and 13 kDa. It contains two low-spin heme C centers, one high-, and one low-spin heme B centers. A full description of the equilibrium redox behavior of the heme centers was obtained for a cbb3 oxidase for the first time. The optical spectrum for each heme center and the corresponding reduction potentials were determined at pH 7: + 195 (heme C), +120 (heme B), -50 (heme C), and -50 mV (heme B3). PMID- 11768748 TI - The contribution of mitochondrial respiratory complexes to the production of reactive oxygen species. AB - This work was focused on distinguishing the contribution of mitochondrial redox complexes to the production of reactive oxygen species (ROS) during cellular respiration. We were able to accurately measure, for the first time, the basal production of ROS under uncoupled conditions by using a very sensitive method, based on the fluorescent probe dichlorodihydrofluorescein diacetate. The method also enabled the detection of the ROS generated by the oxidation of the endogenous substrates in the mitochondrial preparations and could be applied to both mitochondria and live cells. Contrary to the commonly accepted view that complex III (ubiquinol:cytochrome c reductase) is the major contributor to mitochondrial ROS production, we found that complex I (NADH-ubiquinone reductase) and complex II (succinate-ubiquinone reductase) are the predominant generators of ROS during prolonged respiration under uncoupled conditions. Complex II, in particular, appears to contribute to the basal production of ROS in cells. PMID- 11768749 TI - Cerebral cortex synaptic heavy mitochondria may represent the oldest synaptic mitochondrial population: biochemical heterogeneity and effects of L acetylcarnitine. AB - The microheterogeneous nature of intrasynaptic mitochondria has been demonstrated and is widely accepted. However, evidence is still lacking about the role played by the different intrasynaptic mitochondrial subpopulations. The data obtained support the hypothesis that "heavy" mitochondria could represent old mitochondrial populations: in fact, in addition to the well known impairment of typical mitochondrial functions, they possess the highest levels of hydroperoxides and their fatty acids pattern is completely modified. The qualitative and quantitative fatty acid modifications suffered by these organelles deeply altered their protein/lipid ratio, thus modifying their mode of action. The present work also collects a large body of evidence that a subchronic L-acetylcarnitine treatment in 28 days does not structurally affect both nonsynaptic and intrasynaptic mitochondria of normal rat in a "steady-state" metabolic condition. PMID- 11768750 TI - Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin. AB - Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation of biological membranes and the associated organelle dysfunctions. However, the basic mechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weekly injections of iron-dextran alone or in combination with sylibin, a well-known antioxidant, by gavage for 8 weeks. A strict correlation was found between lipid peroxidation and the level of desferrioxamine chelatable iron pool. A consequent derangement in the mitochondrial energy-transducing capability, resulting from a reduction in the respiratory chain enzyme activities, occurred. These irreversible oxidative anomalies brought about a dramatic drop in tissue ATP level. The mitochondrial oxidative derangement was associated with the development of fibrosis in the hepatic tissue. Silybin administration significantly reduced both functional anomalies and the fibrotic process by chelating desferrioxamine chelatable iron. PMID- 11768751 TI - Correlation between decreased expression of mitochondrial F0F1-ATP synthase and low regenerating capability of the liver after partial hepatectomy in hypothyroid rats. AB - In hypothyroid rats, partial hepatectomy does not induce liver regeneration until 120 h after surgical operation. when, instead, in normal rats a complete recovery of the liver mass, in this interval, is observed. In normal rats, a good efficiency of mitochondrial oxidative phosphorylation is needed as an energy source for liver regeneration (Guerrieri, F. et al., 1995); in hypothyroid rats the efficiency of mitochondrial oxidative phosphorylation is low in the 0-120 h interval after partial hepatectomy. This low efficiency of oxidative phosphorylation appears to be related to a low mitochondrial content of F0F1-ATP synthase, in liver of hypothyroid rats, which does not recover after partial hepatectomy. In the liver of hypothyroid rats, low levels of the nuclear-encoded mitochondrial catalytic betaF1 subunit and of its transcript are observed and they do not increase, as occurs in normal rats, after partial hepatectomy. PMID- 11768752 TI - Inactivation of mitochondrial permeability transition pore by octylguanidine and octylamine. AB - Mitochondrial permeability transition occurs through a Ca2+-dependent opening of a transmembrane pore, whose identity has been attributed to that of the adenine nucleotide translocase (ANT). In this work, we induced permeability transition by adding 0.5 microM carboxyatractyloside. The process was evaluated analyzing Ca2+ efflux, a drop in transmembrane electric gradient, and swelling. We found that the amphiphyllic cations octylguanidine and octylamine, at the concentration of 100 microM, inhibited, almost completely, nonspecific membrane permeability. Hexylguanidine, hexylamine, as well as guanidine chloride and hydroxylamine failed to do so. The inhibition was reversed after the addition of 40 mM Li+, Na+ K+, Rb+, or Cs+; K+ was the most effective. We propose that the positive charge of the amines interact with negative charges of membrane proteins, more likely the ADP/ATP carrier, while the alkyl chain penetrates into the hydrophobic milieu of the inner membrane, fixing the reagent. PMID- 11768754 TI - Introduction: our changing views of mitochondria. PMID- 11768753 TI - Interactions between ascorbyl free radical and coenzyme Q at the plasma membrane. AB - A role for coenzyme Q in the stabilization of extracellular ascorbate by intact cells has been recently recognized. The aim of this work was to study the interactions between reduced ubiquinone in the plasma membrane and the ascorbyl free radical, as an approach to understand ubiquinone-mediated ascorbate stabilization at the cell surface. K-562 cells stabilized ascorbate and decreased the steady-state levels of the semiascorbyl radical. The ability of cells to reduce ascorbyl free radical was inhibited by the quinone analogs capsaicin and chloroquine and stimulated by supplementing cells with coenzyme Q10. Purified plasma membranes also reduced ascorbyl free radical in the presence of NADH. Free radical reduction was not observed in quinone-depleted plasma membranes, but restored after its reconstitution with coenzyme Q10. Addition of reduced coenzyme Q10 to depleted membranes allowed them to reduce the signal of the ascorbyl free radical without NADH incubation and the addition of an extra amount of purified plasma membrane quinone reductase further stimulated this activity. Reduction was abolished by treatment with the reductase inhibitor p-hydroximercuribenzoate and by blocking surface glycoconjugates with the lectin wheat germ agglutinin, which supports the participation of transmembrane electron flow. The activity showed saturation kinetics by NADH and coenzyme Q, but not by the ascorbyl free radical in the range of concentrations used. Our results support that reduction of ascorbyl free radicals at the cell surface involves coenzyme Q reduction by NADH and the membrane-mediated reduction of ascorbyl free radical. PMID- 11768755 TI - Calcium-binding properties of the mitochondrial channel-forming hydrophobic component. AB - A hydrophobic, low-molecular weight component extracted from mitochondria forms a Ca2+-activated ion channel in black-lipid membranes (Mironova et al., 1997). At pH 8.3-8.5, the component has a high-affinity binding site for Ca2+ with a Kd of 8 x 10(-6) M, while at pH 7.5 this Kd was decreased to 9 x 10(-5) M. Bmax for the Ca2+-binding site did not change significantly with pH. In the range studied, 0.2 +/- 0.06 mmol Ca2+/g component were bound or one calcium ion to eight molecules of the component. The Ca2+ binding was strongly decreased by 50-100 mM Na+, but not by K+. Treatment of mitochondria with CaCl2 prior to ethanolic extraction resulted in a high level of Ca2+-binding capacity of the partially purified component. Cyclosporin A, a specific inhibitor of the mitochondrial permeability transition, when added to the mitochondrial suspension, decreased the Ca2+ binding activity of the purified extract severalfold. The calcium-binding capability of the partially purified component correlates with its calcium channel activity. This indicates that the channel-forming component might be involved in the permeability transition that stimulates its formation. PMID- 11768756 TI - Cloning and characterization of a 35-kDa mouse mitochondrial outer membrane protein MOM35 with high homology to Tom40. AB - We have cloned a 35-kDa protein from a mouse cDNA library with a 25% overall amino acid identity to yTom40 and 27% identity to nTom40. This homolog toTom40 was named MOM35. It contains two possible start codons 36 amino acids apart from each other. Both the long and the short version of MOM35 can be imported in vitro into mouse mitochondria. The identified protein is imported into the outer mitochondrial membrane and comprises a trypsin-resistance pattern similar to that of nTom40. Tom40 of N. crassa, S. cerevisiae, and the protein identified herein contains a highly conserved region with possible physiological importance. Subsequent investigation has revealed that this region interacts specifically in vitro with preproteins proposed to be imported by a Tom40-dependent pathway. PMID- 11768757 TI - A quantitative approach to membrane binding of human ubiquitous mitochondrial creatine kinase using surface plasmon resonance. AB - We have evaluated surface plasmon resonance with avidin-biotin immobilized liposomes to characterize membrane binding of ubiquitous mitochondrial creatine kinase (uMtCK). While the sarcomeric sMtCK isoform is well known to bind to negatively charged phospholipids, especially cardiolipin, this report provides the first experimental evidence on the membrane interaction of an uMtCK isoform. Qualitative measurements showed that liposomes containing 16% (w/w) cardiolipin bind octameric as well as dimeric human uMtCK and also cytochrome c, but not bovine serum albumin. Quantitative parameters could be derived only for the membrane interaction of octameric human uMtCK using an improved analytical approach. Association and dissociation kinetics of octameric uMtCK fit well to a model for heterogeneous interaction suggesting two independent binding sites. Rate constants of the two sites differed by one order of magnitude, while their affinity constants were both about 80-100 nM. The data obtained demonstrate that surface plasmon resonance with immobilized liposomes is a suitable approach to characterize the binding of peripheral proteins to a lipid bilayer and that this method yields consistent quantitative binding parameters. PMID- 11768758 TI - Mitochondrial calcium signaling driven by the IP3 receptor. AB - Many agonists bring about their effects on cellular functions through a rise in cytosolic [Ca2+] ([Ca2+]c) mediated by the second messenger inositol 1,4,5 trisphosphate (IP3). Imaging studies of single cells have demonstrated that [Ca2+]c signals display cell specific spatiotemporal organization that is established by coordinated activation of IP3 receptor Ca2+ channels. Evidence emerges that cytosolic calcium signals elicited by activation of the IP3 receptors are efficiently transmitted to the mitochondria. An important function of mitochondrial calcium signals is to activate the Ca2+-sensitive mitochondrial dehydrogenases, and thereby to meet demands for increased energy in stimulated cells. Activation of the permeability transition pore (PTP) by mitochondrial calcium signals may also be involved in the control of cell death. Furthermore, mitochondrial Ca2+ transport appears to modulate the spatiotemporal organization of [Ca2+]c responses evoked by IP3 and so mitochondria may be important in cytosolic calcium signaling as well. This paper summarizes recent research to elucidate the mechanisms and significance of IP3-dependent mitochondrial calcium signaling. PMID- 11768759 TI - Mitochondrial calcium in heart cells: beat-to-beat oscillations or slow integration of cytosolic transients? AB - Mitochondria have been implicated in intracellular Ca2+ signaling in many cell types. The inner mitochondrial membrane contains Ca2+-transporting proteins, which catalyze Ca2+ uptake and extrusion. Intramitochondrial (matrix) Ca2+, in turn, regulates the activity of Krebs cycle dehydrogenases and, ultimately, the rate of ATP synthesis. In the myocardium, controversy remains whether the fast cytosolic Ca2+ transients underlying excitation-contraction coupling in beating cells are rapidly transmitted into the matrix compartment or slowly integrated by the mitochondrial Ca2+ transporters. This mini-review critically summarizes the recent experimental work in this field. PMID- 11768760 TI - Mitochondria in Ca2+ signaling and apoptosis. AB - Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injury and programmed cell death; mitochondria play a pivotal role in the regulation of such cytosolic Ca2+ ([Ca2+]c) signals. Mitochondria are endowed with multiple Ca2+ transport mechanisms by which they take up and release Ca2+ across their inner membrane. These transport processes function to regulate local and global [Ca2+]c, thereby regulating a number of Ca2+-sensitive cellular mechanisms. The permeability transition pore (PTP) forms the major Ca2+ efflux pathway from mitochondria. In addition, Ca2+ efflux from the mitochondrial matrix occurs by the reversal of the uniporter and through the inner membrane Na+/Ca2+ exchanger. During cellular Ca2+ overload, mitochondria take up [Ca2+]c, which, in turn, induces opening of PTP, disruption of mitochondrial membrane potential (delta(psi)m) and cell death. In apoptosis signaling, collapse of delta(psi)m and cytochrome c release from mitochondria occur followed by activation of caspases, DNA fragmentation, and cell death. Translocation of Bax, an apoptotic signaling protein from the cytosol to the mitochondrial membrane, is another step during this apoptosis-signaling pathway. The role of permeability transition in the context of cell death in relation to Bcl-2 family of proteins is discussed. PMID- 11768761 TI - MCC and PSC, the putative protein import channels of mitochondria. AB - All but a small fraction of the hundreds of proteins in a mitochondrion are synthesized in the cytoplasm and imported into the organelle. Water-filled channels are integral to the process of translocating proteins since channels can provide an aqueous pathway through the hydrophobic environment of the membrane. The MCC (multiple conductance channel) and PSC (peptide-sensitive channel) are two high-conductance channels previously identified in electrophysiological studies of mitochondrial membranes. MCC and PSC are the putative pores of the import complexes of the inner and outer membranes, respectively. The genetic, biochemical, and biophysical evidence regarding these assignments are summarized herein. These findings support the identification of MCC and PSC as the protein import channels of mitochondria. PMID- 11768762 TI - The local control of cytosolic Ca2+ as a propagator of CNS communication- integration of mitochondrial transport mechanisms and cellular responses. AB - Ca2+ signals propagate in wave form along individual cells of the central nervous system (CNS) and through networks of connected cells of neuronal and multiple glial cell types. In order for wave fronts to convey information, signaling mechanisms are required that allow waves to propagate reproducibly and without decrement in signal strength over long distances. CNS Ca2+ waves are under specific integrated local control, made possible by interactions at local subcellular microdomains between endoplasmic reticulum and mitochondria. Active mitochondria located near the mouth of inositol trisphosphate receptor (InsP3R) channel clusters in glia take up Ca2+, which may prevent a buildup of Ca2+ around the InsP3R channel, thereby decreasing the rate of Ca2+-induced receptor inactivation, and prolonging channel open time. Mitochondria may amplify InsP3 dependent Ca2+ signals by a transient permeability transition in response to Ca2+ uptake into the mitochondrion. Other evidence suggests privileged access into mitochondria for Ca2+ entering neurons by glutamatergic receptor channels. This enables specific signal modulation as the Ca2+ wave is propagated into neurons, such that mitochondria located close to glutamate channels can prolong the neuronal cytosolic response time by successive uptake and release of Ca2+. Disruption of mitochondrial function deregulates the ability of CNS-derived cells to undergo normal Ca2+ signaling and wave propagation. PMID- 11768763 TI - Signals and receptors--the translocation machinery on the mitochondrial surface. AB - Most proteins involved in mitochondrial biogenesis are encoded by the genome of the nucleus. They are synthesized in the cytosol and have to be transported toward and, subsequently, imported into the organelle. This targeting and import process is initiated by the specific mitochondrial targeting signal, which differs pending on the final localization of the protein. The preprotein will be recognized by cytosolic proteins, which function in transport toward the mitochondria and in maintaining the import competent state of the preprotein. The precursor will be transferred onto a multicomponent complex on the outer mitochondrial membrane, formed by receptor proteins and the general insertion pore (GIP). Some proteins are directly sorted into the outer membrane whereas the majority will be transported over the outer membrane through the import channel followed by further distribution of those proteins. PMID- 11768764 TI - Yeast mitochondrial carriers: bacterial expression, biochemical identification and metabolic significance. AB - The genome of Saccharomyces cerevisiae encodes 35 members of a family proteins that transport metabolites and substrates across the inner membranes of mitochondria. They include three isoforms of the ADP/ATP translocase and the phosphate and citrate carriers. At the start of our work, the functions of the remaining 30 members of the family were unknown. We are attempting to identify these 30 proteins by overexpression of the proteins in specially selected host strains of Escherichia coli that allow the carriers to accumulate at high levels in the form of inclusion bodies. The purified proteins are then reconstituted into proteoliposomes where their transport properties are studied. Thus far, we have identified the dicarboxylate, succinate-fumarate and ornithine carriers. Bacterial overexpression and functional identification, together with characterization of yeast knockout strains, has brought insight into the physiological significance of these transporters. The yeast dicarboxylate carrier sequence has been used to identify the orthologous protein in Caenorhabditis elegans and, in turn, this latter sequence has been used to establish the sequence of the human ortholog. PMID- 11768766 TI - Control of the mitochondrial permeability transition pore by high-affinity ADP binding at the ADP/ATP translocase in permeabilized mitochondria. AB - Low levels of ADP binding at the ADP/ATP translocase caused inhibition of the Ca2+-induced permeability transition of the mitochondrial inner membrane, when measured using the shrinkage assay on mitochondria, which have already undergone a transition. Inhibition was prevented by carboxyatractyloside, but potentiated by bongkrekic acid, which increased the affinity for inhibition by ADP. This suggests that inhibition was related to the conformation of the translocase. Ca2+ addition was calculated to remove most of the free ADP. Ca2+ added after ADP induced a slow decay of the inhibition, which probably reflected the dissociation of ADP from the translocator. We conclude that the probability of forming a permeability transition pore (PTP) is much greater when the translocase is in the CAT conformation than in the BKA conformation, and, in the absence of CAT and BKA, the translocator is shifted between the BKA and CAT conformations by ADP binding and removal, even in deenergized mitochondria with no nucleotide gradients. PMID- 11768765 TI - Extramitochondrial porin: facts and hypotheses. AB - Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrial membrane. Several publications have reported extramitochondrial localizations as well, but the evidence was considered insufficient by many, and the presence of porin in nonmitochondrial cellular compartments has remained in doubt for a long time. We have now obtained new data indicating that the plasma membrane of hematopoietic cells contains porin, probably located mostly in caveolae or caveolae-like domains. Porin was purified from the plasma membrane of intact cells by a procedure utilizing the membrane-impermeable labeling reagent NH-SS-biotin and streptavidin affinity chromatography, and shown to have the same properties as mitochondrial porin. A channel with properties similar to that of isolated VDAC was observed by patch-clamping intact cells. This review discusses the evidence supporting extramitochondrial localization, the putative identification of the plasma membrane porin with the "maxi" chloride channel, the hypothetical mechanisms of sorting porin to various cellular membrane structures, and its possible functions. PMID- 11768767 TI - Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes. AB - Studies with electron microscopy have shown that sarcoplasmic reticulum (SR) and mitochondria locate close to each other in cardiac muscle cells. We investigated the hypothesis that this proximity results in a transient exposure of mitochondrial Ca2+ uniporter (CaUP) to high concentrations of Ca2+ following Ca2+ release from the SR and thus an influx of Ca2+ into mitochondria. Single ventricular myocytes of rat were skinned by exposing them to a physiological solution containing saponin (0.2 mg/ml). Cytosolic Ca2+ concentration ([Ca2+]c) and mitochondrial Ca2+ concentration ([Ca2+]m) were measured with fura-2 and rhod2, respectively. Application of caffeine (10 mM) induced a concomitant increase in [Ca2+]c and [Ca2+]m. Ruthenium red, at concentrations that block CaUP but not SR release, diminished the caffeine-induced increase in [Ca2+]m but not [Ca2+]c. In the presence of 1 mM BAPTA, a Ca2+ chelator, the caffeine-induced increase in [Ca2+]m was reduced substantially less than [Ca2+]c. Moreover, inhibition of SR Ca2+ pump with two different concentrations of thapsigargin caused an increase in [Ca2+]m, which was related to the rate of [Ca2+]c increase. Finally, electron microscopy showed that sites of junctions between SR and T tubules from which Ca2+ is released, or Ca2+ release units, CRUs, are preferentially located in close proximity to mitochondria. The distance between individual SR Ca2+ release channels (feet or ryanodine receptors) is very short, ranging between approximately 37 and 270 nm. These results are consistent with the idea that there is a preferential coupling of Ca2+ transport from SR to mitochondria in cardiac muscle cells, because of their structural proximity. PMID- 11768768 TI - Prevention of carcinogenesis by tea polyphenols. AB - Tea, an extract of the leaves of the plant Camellia sinensis, has been considered a medicine and healthful beverage for ages. The beneficial effects of tea are thought to be due to its polyphenolic components. Herein, we discuss the present status of tea as a possible cancer chemopreventive agent, covering basic chemistry and biochemical activity of tea, pharmacokinetics of major tea components, studies in animal and cell lines, epidemiological investigations, and future challenges. Tea is one of the few chemopreventive agents known to have protective effects at different stages of the carcinogenic process. Tea constituents may inhibit this process by modulating signal transduction pathways leading to the inhibition of cell proliferation and transformation and enhancement of apoptosis. These activities may or may not be due to the antioxidative activity of tea polyphenols. The bioavailability and tissue levels of tea polyphenols is a key topic to be studied in order to understand the mechanisms of action of tea and its possible protection against cancer in humans. PMID- 11768770 TI - The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. AB - At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as a treatment to remove the latency of microsomal glucuronidations. Most UGT isoforms appear to have a distinct hepatic and/or extrahepatic expression, resulting in significant expression in kidney, intestine, and steroid target tissues. The gastrointestinal tract possesses a complex expression pattern largely containing members of the UGT1A subfamily. Thus, these forms are poised to participate in the first pass metabolism of oral drugs. The authors and others have identified a significant expression of UGT1A1 in human small intestine, an enzyme possessing considerable allelic variability and a polymorphic expression pattern in intestine. Intestinal glucuronidation therefore plays a major role not only in first pass metabolism, but also in the degree of interindividual variation in overall oral bioavailability. Due to issues such as significant genetic variability and tissue localization in first-pass organs, clearance due to UGT1A1 should be minimized for new drugs. PMID- 11768769 TI - Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). AB - Cellular responses to xenobiotic-induced stress can signal proliferation, differentiation, homeostasis, apoptosis, or necrosis. To better understand the underlying molecular mechanisms after exposure to xenobiotics or drugs, we studied the signal transduction pathways, the mitogen-activated protein kinase (MAPK), and the basic leucine zipper transcription factor Nrf2, activated by different agents in the induction of Phase II drug metabolizing enzymes (DMEs). The MAPKs, characterized as proline-directed serine/threonine kinases, are essential components of signaling pathways that convert various extracellular signals into intracellular responses through serial phosphorylation cascades. Once activated, MAPKs can phosphorylate many transcription factors, such as c Jun, ATF-2, and ultimately lead to changes in gene expression. Two classes of Phase II gene inducers, which are also cancer chemopreventive agents, were studied: (1) the phenolic antioxidants, namely butylated hydroxyanisole (BHA) and its active de-methylated metabolite t-butylhydroquinone (tBHQ), and phenolic flavonoids such as green tea polyphenols (GTP) and (-)-epigallocatechin-3-gallate (EGCG); and (2) the naturally occurring isothiocyanates, namely phenethyl isothiocyanate (PEITC), and sulforaphane. BHA and tBHQ are both well-known phenolic antioxidants used as food preservatives, and strongly activate c-Jun N terminal kinase 1 (JNK1), extracellular signal-regulated protein kinase 2 (ERK2), or p38, in a time- and dose-dependent fashion. Free radical scavengers N-acetyl-L cysteine (NAC), or glutathione (GSH), inhibited ERK2 activation and, to a much lesser extent, JNK1 activation by BHA/tBHQ, implicating the role of oxidative stress. Under conditions where MAPKs were activated, BHA or GTP also activated ARE/EpRE (antioxidant/electrophile response element), with the induction of Phase II genes such as NQO. Transfection studies with various cDNAs encoding wild-type or dominant-negative mutants of MAPKs and/or transcription factor Nrf2, substantially modulated ARE-mediated luciferase reporter activity in the presence or absence of phenolic compounds. Other phytochemicals including PEITC, and sulforaphane, also differentially regulated the activities of MAPKs, Nrf2, and ARE-mediated luciferase reporter gene activity and Phase II enzyme induction. A model is proposed where these xenobiotics (BHA, tBHQ, GTP, EGCG, PEITC, sulforaphane) activate the MAPK pathway via an electrophilic-mediated stress response, leading to the transcription activation of Nrf2/Maf heterodimers on ARE/EpRE enhancers, with the subsequent induction of cellular defense/detoxifying genes including Phase II DMEs, which may protect the cells against toxic environmental insults and thereby enhance cell survival. The studies of these signaling pathways may yield insights into the fate of cells upon exposure to xenobiotics. PMID- 11768771 TI - Mechanisms and clinical implications of renal drug excretion. AB - The body defends itself against potentially harmful compounds like drugs, toxic compounds, and their metabolites by elimination, in which the kidney plays an important role. Renal clearance is used to determine renal elimination mechanisms of a drug, which is the result of glomerular filtration, active tubular secretion and reabsorption. The renal proximal tubule is the primary site of carrier mediated transport from blood to urine. Renal secretory mechanisms exists for, anionic compounds and organic cations. Both systems comprises several transport proteins, and knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past decade. Due to overlapping specificities of the transport proteins, drug interactions at the level of tubular secretion is an event that may occur in clinical situation. This review describes the different processes that determine renal drug handling, the techniques that have been developed to attain more insight in the various aspects of drug excretion, the functional characteristics of the individual transport proteins, and finally the implications of drug interactions in a clinical perspective. PMID- 11768772 TI - Stereochemistry of styrene biotransformation. AB - Metabolism of styrene, an important industrial monomer, is reviewed. Attention is focused on the stereoselectivity of its oxidation to 7,8-styrene oxide as well as on further stereoselective biotransformation by hydrolytic and mercapturic acid pathway. Toxic effects such as mutagenicity, genotoxicity, hepatotoxicity, and pneumotoxicity may be related to the ratio of styrene oxide enantiomers at the target site. In rats formation of the less mutagenic (S)-styrene oxide and a faster detoxication of the (R)-enantiomer is favored. In mice metabolic activation of styrene favors the formation of (R)-styrene oxide but this more toxic enantiomer is detoxified faster, so that a nearly racemic styrene oxide results. Stereochemistry of biotransformation can contribute to the species differences in toxicity but can hardly be interpreted as a crucial factor. Due to lack of relevant data the stereochemistry of human metabolism cannot be interpreted in relation to the toxic effects. PMID- 11768773 TI - Enzymatic aspects of the phenol (aryl) sulfotransferases. AB - The sulfotransferases that are active in the metabolism of xenobiotics represent a large family of enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to phenols, to primary and secondary alcohols, to several additional oxygen-containing functional groups, and to amines. Restriction of this review to the catalytic processes of phenol or aryl sulfotransferases does not really narrow the field, because these enzymes have overlapping specificity, not only for specific compounds, but also for multiple functional groups. The presentation aims to provide an overview of the wealth of phenol sulfotransferases that are available for study but concentrates on the enzymology of rat and human enzymes, particularly on the predominant phenol sulfotransferase from rat liver. The kinetics and catalytic mechanism of the rat enzyme is extensively reviewed and is compared with observations from other sulfotransferases. PMID- 11768774 TI - Genetic variation in the MHC II promoter: lessons for regulation and for comparative genomics. AB - Sequence data have been accumulating that reveal variation in gene promoters of the immune system, notably in MHC class II, cytokines and chemokines. The variation is non-random: it occurs most often in proximity to and within certain regulatory elements such as CRE and NFY (in MHC class II these are respectively the X2 and Y boxes). These are elements that are widely used elsewhere in the genome, and appear to act as rheostats (modulators of expression) in contrast to the type of on-off switch operated by the RFX element that is unique to a single family of promoters such as MHC class II. It is proposed that a complex mouse phenotype described in Prague and elsewhere may reflect this pattern of variation in/around CRE. Such rheostats are expected to operate in other promoters. Their identification will be facilitated by short-range comparisons (e.g. human-chimp), and indeed this is a motive for extending comparative genomics. PMID- 11768775 TI - Expression of human erythropoietin gene in the mammary gland of a transgenic mouse. AB - WAP is being recognized as the principal milk protein expressed in pregnant or lactating females of several mammalian species. Recently, it has been shown that the 6.3-kb 5' untranslated region of the rWAP gene is able to control, and almost completely restrict, the expression of the transgene into the mammary gland of the transgenic animal. We cloned the genomic fragment carrying the rWAP gene locus from the rabbit phage genomic library and used the 8.5-kb long 5' untranslated part of the rWAP gene to target the expression of hEPO, cloned from the human phage genomic library, into the mammary gland of the mouse. The vectors, carrying either the hEPO gene or the rWAP-hEPO hybrid gene, were injected into the mouse ova, and 12 transgenic animals were identified by PCR and Southern blot from the progeny of 168 tested littermates. Transgenic mice were viable, fertile and displayed a normal development. Recombinant human erythropoietin was produced in the milk of a transgenic mouse female at a secretion level of 5.3 mIU/ml, as detected by ELISA. Despite the low production of the transgenic glycoprotein in the milk we demonstrate that the hybrid gene can be expressed in the mammary gland of the host animal. Thus, WAP-based recombinant vectors, with additional optimizing modifications, can be useful for production of therapeutic proteins in the transgenic mammals. PMID- 11768776 TI - Allosteric modulation of GABAA receptor by somatostatin is altered under stress in rat brainstem. AB - This study was conducted to investigate somatostatin modulation of GABAA receptor binding in several rat brainstem structures, located principally in the mesencephalon, after exposure to acute immobilization stress (single 1-hour session). Animals were randomly assigned to either control or stress conditions and changes in specific binding of the GABAA receptor as labelled with TBPS were assessed by in vitro quantitative autoradiography with the aid of a computer assisted image analysis system. Exposure to immobilization stress led to a significant increase in [35S]TBPS binding site density in the SN of stressed rats compared to controls. In the other brainstem structures analysed, specific binding of [35S]TBPS remained unchanged in stressed rats. Furthermore, the results of the present in vitro study demonstrate an alteration of the modulatory effect of somatostatin on the GABAA receptor complex in the SN of stressed rats as compared to controls. This apparent alteration of allosteric effects of GABA receptor-somatostatin in the SN of stressed rats was eliminated in the presence of 1 micromolar concentration of GABA. Taken together, these data provide the first evidence of stress-induced alteration of allosteric effects of GABA somatostatin in the rat mesencephalon. Furthermore, they also demonstrate that the tetradecapeptide somatostatin is particularly effective in modifying the [35S]TBPS binding to the GABAA receptor in this cerebral region. PMID- 11768777 TI - Cells of porcine epidermis and corneal epithelium are not recognized by human natural anti-alpha-galactoside IgG. AB - Human natural antibodies against Galalphal,3Gal-R are mainly responsible for hyperacute rejection of xenografts transplanted to the human host. In addition to the anti-alpha-Gal activity, human serum also contains anti-beta-Gal IgG fractions. Employing biotinylated IgG subfractions with anti-alpha- and anti-beta Gal activity purified from human natural IgG, we have studied expression of reactive epitopes in porcine and human skin, porcine cultured keratinocytes and porcine and human cornea, porcine liver and human lacrimal gland, tear fluid and capillaries. No reactivity of porcine and human epidermis as well as anterior corneal epithelium was observed for human anti-alpha-Gal IgG. Serving as positive control, porcine capillaries gave the expected signal with the anti-alpha-Gal antibody. The anti-beta-Gal subfraction recognized cell nuclei in the epidermis of both these species. The pig liver cells interacted with antibodies against alpha- and beta-galactosides like cells of the human lacrimal gland. alpha galactoside-reactive glycoproteins were also detected in the human tear fluid. The carbohydrate specificity of the reaction was ascertained by using melibiose as competitive sugar for alpha-galactoside-mediated binding. These results reveal the presentation of Galalpha1,3Gal in epithelial cells of human lacrimal gland, its biosynthetic origin being unclear. With respect to a potential clinical perspective, the given results facilitate consideration of the use of porcine epidermal cells in engineering of non-permanent wound covers to improve treatment. PMID- 11768778 TI - Detection of minimal bone marrow infiltration in patients with localized and metastatic Ewing sarcoma using RT-PCR. AB - Ewing sarcoma and related neoplasias are characterized by the presence of specific chromosomal translocations resulting in EWS/ETS gene rearrangements. Created EWS/ETS-oncogene fusion transcripts can be detected in up to 98% of ESFT and provide tumour-specific markers useful in diagnostics. Using RT-PCR for detection of this aberration we can reveal minimal amounts of tumour cells contaminating BM, blood or apheresis products. We have examined BM samples from 22 patients (21 newly diagnosed and one recurrent disease) with histologically confirmed ESFT for the presence of contaminating tumour cells in BM at the time of diagnosis. Sixteen patients presented with localized disease, six had distant metastases at the first presentation. Ewing sarcoma cells were detected in the BM of 5/16 (31%) patients with localized disease and 3/6 (50%) with clinically detectable metastases at diagnosis. BM smears prepared from the same aspirates evaluated by light microscopy were all negative, even in two patients with multiple bone disease. We have confirmed the high sensitivity of the RT-PCR assay for detection of minimal BM infiltration in localized and metastatic ESFT. We have found that more than a quarter of patients with localized ESFT have minimal BM infiltration. Although the clinical significance of the minimal disease detected at the molecular level remains unknown, RT-PCR evaluation may enable better stratification of patients into risk groups in the future. PMID- 11768779 TI - New monoclonal antibodies recognizing the p53 tumour suppressor protein homologue p73. PMID- 11768780 TI - New monoclonal antibodies recognizing the adaptor protein LAT. PMID- 11768781 TI - Sleep-wake function in children with neurodevelopmental and psychiatric disorders. AB - Sleep disturbance is commonly described in children with developmental problems of a primarily physical or psychiatric nature. Its persistence is likely to adversely affect cognition, mood, behavior, and family functioning. Therefore, accurate diagnosis of the underlying sleep disorder, with prompt and effective treatment, can be considered essential for overall care. Reports of sleep disturbance in various neurodevelopmental and psychiatric disorders of childhood are outlined. The origins of the disturbance in each condition may lie in the disorder itself, the child's circumstances, or reflect comorbidity. Each contributory factor has implications for treatment strategies and outcome. Much remains to be discovered about childhood sleep disorders. However, sufficient information is already known to significantly improve their recognition and management if professional education in such matters improves. PMID- 11768782 TI - Narcolepsy in children. AB - Core symptoms of narcolepsy are similar in children compared with adults, but expression may be different due to more severe manifestations, maturational factors, and the significant impact of symptoms on behavior and academic performance. Diagnosis of narcolepsy in children is often challenging and requires a detailed history followed by polysomnography and the Multiple Sleep Latency Test. Management involves a comprehensive approach, including patient and family education and emotional support; behavioral strategies, such as good sleep hygiene and planned naps; and pharmacologic intervention. Despite dramatic progress recently in understanding the etiology of human narcolepsy through molecular genetic investigations, the disorder remains a chronic and often disabling disease with major impact on the lives of children and their families. PMID- 11768784 TI - Assessment of sleepiness in children. AB - Excessive sleepiness is a common but under-recognized problem in children. This article examines the clinical and laboratory evaluation of sleepiness in children, including the use of polysomnography, the multiple sleep latency test, and other varieties of neurophysiologic testing. Where applicable, technical aspects of laboratory testing are reviewed. Alternative laboratory and neurobehavioral techniques used to investigate daytime sleepiness are also briefly covered. PMID- 11768783 TI - Upper airway resistance syndrome in children: a clinical review. AB - Upper airway resistant syndrome (UARS) is more common in children than is obstructive sleep apnea syndrome (OSAS). Age will color the symptoms associated with the syndrome. UARS must be looked for in families with adult sleep disordered breathing. Polygraphic recording during sleep will show flow limitation with usage of nasal cannula/pressure transducer system, but the abnormal breathing during sleep may be indicated also by burst of tachypnea without saturation drops. Esophageal pressure monitoring may be the only way to confirm a suspected diagnosis. A mild developmental anomaly of the craniofacial skeleton is often seen in these children even in the presence of enlarged tonsils and adenoids. Children with sleep-disordered breathing should have a maxillomandibular examination to assess the need for orthodontic treatment to expand the oral cavity. PMID- 11768785 TI - Circadian rhythms and circadian rhythm disorders in children and adolescents. AB - A clinically applicable review of circadian rhythm physiology is presented, including a detailed examination of the interaction of circadian and homeostatic systems and the maturation of the circadian system from preconception through adolescence. Emphasis is placed on the clinical evaluation gathering information through the history, sleep log, and if necessary, actigraphy and polysomnography. Circadian disorders, including advanced sleep phase syndrome, circadian disorders seen in blind children, delayed sleep phase syndrome, and non-24-hour sleep phase are described. Case descriptions of each are provided. Treatment and interventions for these disorders are described, including the importance of education, light therapy, sleep-wake schedule adjustments, and the occasional use of medications, such as sedative hypnotics and melatonin. PMID- 11768786 TI - The relationship between sleep and epilepsy. AB - Seizures occur extensively during sleep or on awakening in a substantial proportion of patients with epilepsy. Interictal epileptiform discharges are also influenced by sleep and sleep deprivation. Continuous spike-waves in slow-wave sleep are the hallmark of Landau-Kleffner syndrome and ESES (Electrical Status in Slow Sleep). Sleep deprivation is known to influence not only the occurrence but also the symptomatology of epileptic seizures. Sleep architecture and daytime alertness are influenced by seizures and antiepileptic medications. This review examines the clinical and basic science aspects of this relationship between sleep and epilepsy. PMID- 11768787 TI - Parasomnias--an update. AB - Primary parasomnias are a group of sleep-related clinical disorders that occur in otherwise healthy children, which may be provoked by a variety of physical, psychosocial, and environmental stimuli. In typical cases, additional investigations are not necessary, and treatment should be instituted with the aim of reducing the frequency and adverse consequences of the parasomnia. In patients with co-existing clinical disorders, parasomnias need to be distinguished from symptoms of the underlying disorder. This article provides a brief review of the recent literature regarding parasomnias, and a clinically oriented approach to the management of parasomnias in patients with co-existing clinical disorders. PMID- 11768788 TI - Sleep disorders in children with neurologic diseases. AB - Pediatric neurologic diseases are often associated with different kinds of sleep disruption (mainly insomnia, less frequently hypersomnia or parasomnias). Due to the key-role of sleep for development, the effort to ameliorate sleep patterns in these children could have important prognostic benefits. Study of sleep architecture and organization in neurologic disorders could lead to a better comprehension of the pathogenesis and a better treatment of the disorders. This article focuses on the following specific neurologic diseases: nocturnal frontal lobe epilepsy and abnormal motor behaviors of epileptic origin, evaluating differential diagnosis with parasomnias; achondroplasia, confirming the crucial role of craniofacial deformity in determining sleep-disordered breathing; neuromuscular diseases, mainly Duchenne's muscular dystrophy and myotonic dystrophy; cerebral palsy, evaluating either the features of sleep architecture and the importance of the respiratory problems associated; headaches, confirming the strict relationships with sleep in terms of neurochemical and neurobehavioral substrates; and finally a review on the effectiveness of melatonin for sleep problems in children with neurologic syndromes and mental retardation, blindness, and epilepsy. PMID- 11768789 TI - Quality factors for alpha particles emitted in tissue. AB - A concept of a mean or dose averaged quality factor was defined in ICRP Publication 26 using relationships for quality factor as a function of LET. The concept of radiation weighting factors, wR, was introduced in ICRP Publication 60 in 1990. These are meant to be generalized factors that modify absorbed dose to reflect the risk of stochastic effects as a function of the quality of the radiation incident on the body or emitted by radioactivity within the body. The values of wr are equal to 20 for all alpha particles externally or internally emitted. This note compares the dose averaged quality factor for alpha particles originating in tissue using the old and revised recommendations for quality factor as a function of LET. The dose averaged quality factor never exceeds 20 using the old recommendations and is never less than 20 with the revised recommendations. PMID- 11768790 TI - Sorption of tin on human teeth. AB - The sorption of tin ions on human teeth from water and other drinks has been studied by the radioactive tracer technique using the isotope 113Sn (T(1/2) = 115.1 d) as a tracer. The tooth holds a minimum amount of tin from coffee and a maximum amount is held from water and from tea with sugar. The same technique was also used to study the desorption of tin already taken up on the teeth. It has been found that sorbed tin is hardly desorbed from the teeth specimens. The high uptake of tin on human teeth from various drinks showed that teeth act as a natural sieve holding trace elements. PMID- 11768791 TI - An evaluation of two sample preparation methods for measuring 3H and 14C in incinerator ash and spent lime. AB - This paper compares the performance of two methodologies, oxidation and gel suspension, for measuring the 3H and 14C specific activity in incinerator ash and lime. The two methods were judged on the basis of the count time needed to achieve a specified minimum detectable concentration. Both methods involve pretreatment of the sample matrix followed by liquid scintillation counting. Both methods perform adequately for measuring 3H in spent lime, but only oxidation delivers adequate sensitivity for the more demanding 14C case. In addition, the gel suspension method fails to detect over 95% of the 3H seen by the oxidation method in incinerator ash. PMID- 11768792 TI - Bias in concentration estimates due to nonconstant flow rate during particulate air sampling. AB - Correction for a nonconstant flow rate during particulate air sampling is often done by taking the arithmetic average of the initial and final flow rates. This average is then used in concentration calculations as if the flow rate had been constant at that value during the entire sampling period. For long-lived activity this approach is reasonable, but for shorter-lived activity and longer sampling times the estimated concentrations can be biased low. This note examines the magnitude of this bias, and also provides expressions for estimating the concentration, given an observed count, assuming an exponential flow rate time dependence. One expression uses an estimate of the exponential time-dependence, while another expression uses a linear approximation for the flow rate time dependence. The parameters used in these expressions are estimated from the same initial and final flow rates used in the arithmetic average. PMID- 11768793 TI - International symposium focuses on global nuclear terrorism. PMID- 11768794 TI - Estimates of radiological risk from depleted uranium weapons in war scenarios. AB - Several weapons used during the recent conflict in Yugoslavia contain depleted uranium, including missiles and armor-piercing incendiary rounds. Health concern is related to the use of these weapons, because of the heavy-metal toxicity and radioactivity of uranium. Although chemical toxicity is considered the more important source of health risk related to uranium, radiation exposure has been allegedly related to cancers among veterans of the Balkan conflict, and uranium munitions are a possible source of contamination in the environment. Actual measurements of radioactive contamination are needed to assess the risk. In this paper, a computer simulation is proposed to estimate radiological risk related to different exposure scenarios. Dose caused by inhalation of radioactive aerosols and ground contamination induced by Tomahawk missile impact are simulated using a Gaussian plume model (HOTSPOT code). Environmental contamination and committed dose to the population resident in contaminated areas are predicted by a food-web model (RESRAD code). Small values of committed effective dose equivalent appear to be associated with missile impacts (50-y CEDE < 5 mSv), or population exposure by water-independent pathways (50-y CEDE < 80 mSv). The greatest hazard is related to the water contamination in conditions of effective leaching of uranium in the groundwater (50-y CEDE < 400 mSv). Even in this worst case scenario, the chemical toxicity largely predominates over radiological risk. These computer simulations suggest that little radiological risk is associated to the use of depleted uranium weapons. PMID- 11768795 TI - Update on Internet use. PMID- 11768796 TI - Photon specific absorbed fractions calculated in the trunk of an adult male voxel based phantom. AB - A new approach for calculating internal dose estimates was developed through the use of a more realistic computational model of the human body. The study demonstrates the capability of building a patient-specific phantom with voxel based data for the simulation of radiation transport and energy deposition using Monte Carlo methods such as the MCNP-4B code. MCNP-4B was used to calculate absorbed fractions for photons in a voxel-based phantom, and values were compared to reference values from traditional phantoms used for many years. Results obtained in general agreed well with previous values, but considerable differences were found in some cases due to two major causes; differences in the organ masses between the phantoms and the occurrence of organ overlap in the voxel-based phantom (which is not well modeled in the mathematical phantoms). These new techniques offer promise of developing a new generation of more realistic phantoms for internal, as well as external, dose assessment. The principal area of implementation in internal dose assessment should be the development of patient-specific dose estimates in nuclear medicine therapy, such as radioimmunotherapy (RIT). However, as new voxel-based phantoms for different individuals can be developed, they may also be used with the techniques developed here to derive new absorbed fractions and replace the traditional values usedfor other applications in internal and external dose assessment, which have been based on mathematical constructs that are not always very representative of real human organs. PMID- 11768797 TI - Volume and activity of buried transuranic-contaminated wastes at U.S. Department of Energy facilities. AB - From the 1940's through the 1970's, radioactive wastes meeting the current definition of transuranic wastes were disposed of by shallow land burial and other techniques at a number of sites owned and operated by the federal government in support of the nuclear weapons program. After transuranic wastes were identified as a separate category of radioactive wastes (distinct from low level wastes) in 1970 by the U.S. Atomic Energy Commission, they were generally segregated and placed in retrievable storage pending the availability of a geologic repository. Updated information on buried transuranic wastes was recently developed to support future decisions on how to manage these materials. This paper summarizes the approach used to develop this information for U.S. Department of Energy facilities and presents the volumes and transuranic activities of these wastes. The total volume of buried transuranic wastes at DOE sites is approximately 126,000 m3 with a much smaller volume (about 11,000 m3) disposed of at intermediate depths. The reported transuranic activity in these previously disposed of wastes is about 28,000 TBq. PMID- 11768798 TI - Characterization of electromagnetic interference of medical devices in the hospital due to cell phones. AB - Concern over electromagnetic interference with medical devices due to cell phone emissions has stemmed from anecdotal reports and unpublished observations of hospital staff. In an effort to characterize electromagnetic interference concerns, representative medical devices from four large teaching hospitals were exposed to standard North American and European communication signal emissions. Of 33 medical devices tested, only 4 showed disruption of critical function due to cell phone emissions at a distance of 25 cm or greater. Although other cases of electromagnetic interference were observed, these were not critically disruptive and mainly occurred when the transmitters were at full power and placed 5 cm or closer to the medical device. Overall, no cell phone signal was exempt from producing electromagnetic interference effects. While sensitive medical devices were often affected by more than one signal type, the effects were not entirely predictable based upon the results of other signals or related medical device units or models. Because a comprehensive analysis of all medical devices in all possible electromagnetic environments was not performed, the data presented here are only intended to provide a general idea of the magnitude of electromagnetic interference effects that might be encountered in a hospital environment, as well as a standard protocol for clinical engineering groups to perform ad hoc electromagnetic interference surveys and methods to manage and/or eliminate electromagnetic interference with appropriate system engineering design including supplementary communication infrastructure, medical device shielding and positioning, and appropriate cell phone user guidelines. PMID- 11768799 TI - Influence of room geometry and ventilation rate on airflow and aerosol dispersion: implications for worker protection. AB - Knowledge of dispersion rates and patterns of radioactive aerosols and gases through workrooms is critical for understanding human exposure and for developing strategies for worker protection. The dispersion within rooms can be influenced by complex interactions between numerous variables, but especially ventilation design and room furnishings. For this study, dependence of airflow and aerosol dispersion on workroom geometry (furnishings) and ventilation rate were studied in an experimental room that was designed to approximate a plutonium laboratory. Three different configurations of simulated gloveboxes and two ventilation rates (approximately 6 and 12 air exchanges per hour) were studied. A sonic anemometer was used to measure airflow parameters including all three components of air velocity vectors and turbulence intensity distributions at multiple locations and heights. Aerosol dispersion rates and patterns were measured by releasing aerosols multiple times from six different locations. Aerosol particle concentrations resolved in time and space were measured using 16 multiplexed laser particle counters. Comparisons were made of air velocities, turbulence, and aerosol transport across different ventilation rates and room configurations. A strong influence of ventilation rate on aerosol dispersion rates and air velocity was found, and changes in room geometry had significant effects on aerosol dispersion rates and patterns. These results are important with regards to constant evaluation of placement of air sampling equipment, benchmarking numerical models of room airflow, and design of ventilation and room layouts with consideration of worker safety. PMID- 11768800 TI - The Gaussian atmospheric transport model and its sensitivity to the joint frequency distribution and parametric variability. AB - Reconstructed meteorological data are often used in some form of long-term wind trajectory models for estimating the historical impacts of atmospheric emissions. Meteorological data for the straight-line Gaussian plume model are put into a joint frequency distribution, a three-dimensional array describing atmospheric wind direction, speed, and stability. Methods using the Gaussian model and joint frequency distribution inputs provide reasonable estimates of downwind concentration and have been shown to be accurate to within a factor of four. We have used multiple joint frequency distributions and probabilistic techniques to assess the Gaussian plume model and determine concentration-estimate uncertainty and model sensitivity. We examine the straight-line Gaussian model while calculating both sector-averaged and annual-averaged relative concentrations at various downwind distances. The sector-average concentration model was found to be most sensitive to wind speed, followed by horizontal dispersion (sigmaZ), the importance of which increases as stability increases. The Gaussian model is not sensitive to stack height uncertainty. Precision of the frequency data appears to be most important to meteorological inputs when calculations are made for near field receptors, increasing as stack height increases. PMID- 11768801 TI - Assessment of the natural radioactivity and its radiological hazards in Shewa Shahbaz Garhi igneous complex, Peshawar Plain, NW Pakistan. AB - Forty-two representative rock samples used for construction purpose were collected from the quarries and outcrops of the rock units forming the Shewa Shahbaz Garhi igneous complex, North-West Pakistan. Radioactivity of terrestrial radionuclides (238U, 232Th, and 40K) was measured in these samples using gamma ray spectrometry system with an HPGe detector. The samples showed fairly high mean concentrations of 51 +/- 16 Bq kg(-1) of 238U, 70 +/- 20 Bq kg(-1) of 232Th and 1,272 +/- 367 Bq kg(-1) of 40K. Mean absorbed gamma dose rate in air of 119 +/- 29 nGy h(-1) was found. Assessment of radiological hazards was made by calculating radium equivalent activities with external and internal hazard indices. The calculations showed radium equivalent activity ranging from 52 to 346 Bq kg(-1). External and internal hazard indices ranging from 0.14 to 0.94 and 0.17 to 1.1, respectively, were found. PMID- 11768802 TI - A survey of background radiation dose rates and radioactivity in Tanzania. AB - Potential terrestrial sources of naturally occurring elevated radiation levels have been identified in Tanzania. Thus, efforts are currently being undertaken to create a natural radiation database, in the form of a radiation level map of natural radioactivity, to be used to assess the associated radiation risk to public and workers. Background radiation dose rate was determined with thermoluminescent dosimeters for 7 y (1993-1999) in five stations. The average background radiation dose rates for these stations were as follows: Tropical Pesticides Research Institute (TPRI) (102 +/- 7 nGy h(-1)), Same (98 +/- 2 nGy h( 1)), Namanga (98 +/- 5 nGy h(-1)), University of Dar Es Salaam (99 +/- 2 nGy h( 1)), and Kilimanjaro Christian Medical Center (121 +/- 3 nGy h(-1)). These stations were found convenient from an economic point of view since the project has no funds to cover wider and/or more remote areas in Tanzania. For the sake of comparison, similar measurements were made for the same period at Minjingu phosphate mine. The mine was one of the suspected areas with elevated levels of natural radioactivity. The radiation dose rate measured in this mine was about fourteen times higher (1,415 +/- 28 nGy h(-1)) than the average value obtained in northern Tanzania (98 nGy h(-1)). The high average activity levels of phosphate (5760 +/- 107 Bq kg(-1) for 261Ra, 497 +/- 5 Bq kg(-1) for 228Ra, 350 +/- 6 Bq kg(-1) for 228Th, and 280 +/- 5 Bq kg(-1) for 40K) and radiation dose rate recorded show that Minjingu phosphate mine has higher values than the highest radioactivity in phosphate compiled by the United Nations Scientific Committee on the Effect of Atomic Radiation. In view of these findings, a comprehensive risk management strategy for reduction of radiation risk to the public and mine workers should be put in place. Efforts are currently being made to seek support to improve the background radiation database for subsequent assessment of radiation risk to miners and the societies in the vicinity of these mines in Tanzania. PMID- 11768803 TI - First international intercomparison of luminescence techniques using samples from the Techa River Valley. AB - Bricks collected from a contaminated village (Muslyumovo) of the lower Techa river valley, Southern Urals, Russia, were measured using thermoluminescence and optically stimulated luminescence by four European laboratories and a U.S. laboratory to establish and compare the applied dose reconstruction methodologies. The bricks, collected from 60-100-year-old buildings, had accumulated a relatively high dose due to natural sources of radiation in the brick and from the surrounding environment. This work represents the results of a first international intercomparison of luminescence measurements for bricks from the Southern Urals. The luminescence measurements of absorbed dose in bricks collected from the most shielded locations of the same buildings were used to determine the background dose due to natural sources of radiation and to validate the age of the bricks. The absorbed dose in different bricks measured by four laboratories using thermoluminescence and optically stimulated luminescence at a depth of 10 +/- 2.5 mm from the exposed brick surface agreed within +/-21%. After subtraction of the natural background dose, the absorbed dose in brick due to contaminated river sediments and banks was calculated and found to range between 150 and 200 mGy. The cumulative doses in brick due to man-made sources of radiation at 100 and 130 mm depths in the bricks were also measured and found to be consistent with depth dose profiles calculated by Monte Carlo simulations of photon transport for possible source distributions. PMID- 11768804 TI - Handling and culture of bovine embryos: survey of media used by 26 embryo transfer companies in the USA. AB - Embryo transfer has evolved from a few highly centralized clinics to a widespread number of clinics offering both clinic and on-the-farm services. Practitioners in the field have made very few changes in the handling and culture of embryos. A short review of general handling techniques, plus a survey of media used by 26 companies in the USA, is presented here. Currently, phosphate-bufferend saline (PBS) plus two other commercially available media (EMCARE and ViGro) are used by these companies. Fourteen different combinations of these products were reported and only 11 of the 26 consistently used the same medium for flushing, culture and freezing. PMID- 11768805 TI - Splitting and biopsy for bovine embryo sexing under field conditions. AB - Improvements on embryo micromanipulation techniques led to the use of embryo bisection technology in commercial embryo transfer programs, and made possible the direct genetic analysis of preimplantation bovine embryos by biopsy. For example, aspiration and microsection, allow bovine embryos sexing by detection of male-specific Y-chromosome in a sample of embryonic cells. We report on the application of the methodologies of splitting and biopsy of bovine embryos in field conditions, and on the results of embryo sex determination by the polymerase chain reaction (PCR). Pregnancy rates achieved with fresh bisected or biopsied embryos (50 to 60%) were similar to the fresh intact embryos (55 to 61%). The PCR protocol used for embryo sexing showed 92% to 94% of efficiency and 90 to 100% of accuracy. These results demonstrate these procedures are suitable for use in field conditions. PMID- 11768806 TI - Practical considerations of embryo manipulation: preimplantation genetic typing. AB - In the past years, research in embryo technologies is moving to the establishment of preimplantation genetic typing or also denominated preimplantation genetic diagnosis (PGD). The objectives of these tests are the prevention of genetic diseases transmission and the prediction of phenotypic characteristics, as well as sex determination, genetic disorders and productive and reproductive profiles, prior to the embryo transfer or freezing, during early stages of development. This paper points out the state-of-the-art of PGD, mainly in cattle and discuss the perspectives of multiloci genetic analysis of embryos. PMID- 11768807 TI - Factors affecting frozen and fresh embryo transfer pregnancy rates in cattle. AB - The effects of a large number of factors on the pregnancy rates of fresh and frozen cattle embryos were examined over a period of years at several different locations. For fresh embryos, overall pregnancy rates were 68.3% (n=9023) and 77.1% (n=2650) at different locations and time periods. Frozen-thawed embryo pregnancy rates were 56.1% (n=3616) in The Netherlands and 58.4% (n=5297) and 68.7% (n=774) for two studies in the United States. Pregnancy rates of surgical versus nonsurgical transfers were very similar. There were no differences in the pregnancy rates of beef versus dairy embryos, but the pregnancy rate was higher in dairy and beef heifers and beef cows than in dairy cows. Although on-farm pregnancy rates in California were higher than in the northeast United States, there was no influence of season on pregnancy rate. Estrous asynchrony between plus and minus 24 h did not affect pregnancy rate for frozen-thawed or fresh embryos. Neither breed nor parity of recipients affected the influence of asynchrony on pregnancy rates. Embryo grade was a significant factor in pregnancy rate for both fresh and frozen-thawed embryos, but neither embryo stage nor age was a significant factor. Pregnancy rate was not affected by holding embryos after flushing for up to 3 h prior to freezing. PMID- 11768808 TI - Use of pregnancy specific proteins and progesterone assays to monitor pregnancy and determine the timing, frequencies and sources of embryonic mortality in ruminants. AB - Profiles of pregnancy specific proteins in relation to pregnancy status (pregnancy, early or late embryonic mortality, later abortions) have been described in several ruminant species. In field studies, the use of pregnancy specific proteins in combination with P4 measurements is useful to identify the factors (environmental/genetic) influencing specifically the frequencies of early and/or late embryonic mortality. This is illustrated from field studies performed in temperate and sub-tropical environments in high producing dairy cows. Such studies may help to define practical measures to suppress or lower the negative effects of risks factors on fertility. PMID- 11768809 TI - Uterine-conceptus interactions and reproductive failure in cattle. AB - The dialogue between trophectoderm cells of the conceptus and epithelial cells of the endometrium is critical to CL maintenance and embryo survival. The signal transduction mechanisms by which bovine interferon (IFN)-tau regulates cyclooxygenase (COX)-2 expression and secretion of prostaglandin F2alpha (PGF2alpha) in bovine endometrial (BEND) cells is examined. Stimulation of Protein Kinase C with a phorbol ester (phorbol 12, 13 dibutyrate [PDBu]) activates COX-2 gene expression and PGF2alpha secretion via the mitogen-activated protein kinase (MAPK) pathway. Interferon-tau attenuates PDBu activation of PGF2alpha secretion, but this inhibitory effect appears to be independent of the MAPK pathway. Embryonic IFN-tau, acting through a Type I IFN receptor, activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway resulting in activation or repression of interferon-stimulated genes. Experimental evidence is provided that IFN-tau regulation of STATs regulates gene expression of COX-2 in a manner that decreases secretion of PGF2alpha. Maternal regulation of the antiluteolytic pathway is discussed relative to the ability of the polyunsaturated fatty acid, eicosapentaenoic (EPA), to decrease endometrial secretion of PGF2alpha and progesterone to increase both conceptus development and IFN-tau secretion. PMID- 11768810 TI - Antiluteolytic strategies to improve fertility in cattle. AB - During early pregnancy, a "critical period" may be defined between Days 15 and 17. Embryonic mortality associated with this period causes significant economic losses to the cattle industry. During this period, the endometrium will follow a default program to release luteolytic pulses of PGF2alpha, unless the conceptus sends appropriate antiluteolytic signals to block PGF2alpha, production. Maintenance of pregnancy is dependent on a successful blockage of endometrial PGF2alpha production. Biology of the critical period is complex and multifactorial. Endocrine, cellular and molecular factors, both from maternal and conceptus origins act in concert to determine whether luteolysis or maintenance of pregnancy will prevail. Understanding the influences of such factors in the biology of the critical period allowed researchers to produce a series of strategies aiming to favor maintenance of pregnancy in lieu of luteolysis. Strategies include hormonal and nutritional manipulations to decrease plasma concentrations of estradiol 17beta (E2) while increasing those of progesterone (P4), and inhibiting the PGF2alpha-synthesizing enzymatic machinery in the endometrium during the critical period. Experimental results indicate that use of such strategies has improved pregnancy rates following artificial insemination and embryo transfer programs. PMID- 11768811 TI - Identified and unidentified challenges for reproductive biotechnologies regarding infectious diseases in animal and public health. AB - The aim of the present paper is to review the known and theoretical risks for in vivo derived and in vitro produced embryos as well as for nuclear transferred or transgenic embryos in terms of animal diseases or diseases of public health consequence. For in vivo derived embryos, a considerable number of experiments and scientific investigations have resulted in recommended guidelines and procedures that ensure a high level of safety. The effectiveness of these measures has been validated by field experience with the safe transfer of several million embryos over the past three decades. In vitro produced embryos have several characteristics that differentiate them from the former, in particular a structure of the zona pellucida that results in a more frequent possible association of pathogens with the embryo. However, the guidelines prescribed by the IETS, the international standard setting body (OIE) and existing national regulatory frameworks are in place to minimize the risk of disease transmission. No specific public health risks have been identified to date with respect to in vivo or in vitro derived embryos. In regard to nuclear transferred and transgenic embryos, theoretical risks have been identified in relation to the potential effects on some intrinsic viruses such as endogenous retroviruses but very little targeted experimental work has been carried out on infectious diseases that could have adverse consequences on animal or human health. Although there has been no report of such adverse consequences associated with the limited number of animals produced to date by such reproductive technologies, a precautionary approach is warranted given the potential negative impacts and it would be prudent to restrict at this stage, the international movement of such "manipulated" embryos. PMID- 11768812 TI - Embryo transfer in Bos indicus cattle. AB - In the present short review superovulation treatments commonly used for Bos taurus and/or Bos indicus will be addressed with emphasis in recent superstimulation protocols associated with pharmacological manipulation of the follicular dynamics to improve donor management and potentially embryo yield. Results obtained after superovulation treatments in which the time of LH surge is selectively delayed as an attempt to improve embryo yield are presented and discussed. PMID- 11768813 TI - Ileocecectomy is definitive treatment for advanced appendicitis. AB - Although appendectomy is the most commonly performed emergency operation septic complications of appendectomy remain a major source of morbidity. Historically, advanced appendicitis has been treated by appendectomy with cecostomy and/or drainage tubes. Our objective was to evaluate the use of ileocecal resection for the immediate treatment of advanced appendicitis. We examined the cases of all patients undergoing ileocecal resection for appendicitis from August 1989 through April 2000. There were 92 patients (60 male and 32 female) with a median age of 34 (range 6-71). Abdominal pain was present in 98 per cent of patients with duration of 5.1+/-0.6 days. Right lower quadrant tenderness was present in 91 per cent with accompanying right lower quadrant mass in 30 per cent. Temperature on admission was 38.0+/-0.1 degrees C with a white blood cell count of 15,300+/-500. Preoperative radiological studies included abdominal X-rays (33), contrast enemas (two), CT scans (41), and abdominal ultrasound (17); these studies yielded a correct preoperative diagnosis in 89 per cent. Previous appendectomy had been performed in six patients with failed percutaneous drainage of intra-abdominal abscesses in five. There were 94 cecal resections performed in 92 patients. The extent of surgical resection varied between patients and ranged from partial cecectomy (34) to ileocecectomy (55) to ileocecectomy with diverting ileostomy (five). Intra-abdominal abscesses were present at operation in 46 cases (50%), and drains were placed in 38 (41%). Skin incisions were packed open in most cases (65); there was skin closure in 27. There was no mortality encountered in this period. There were 25 complications in 23 patients (25%). Complications included postoperative abscess (10; 11%), wound infection (10; 11%), partial small bowel obstruction (two) and pulmonary embolus (one). Reoperation was required in seven patients and CT-guided percutaneous drainage in five patients. Anastomic leaks occurred in two cases of partial cecectomy and required conversion to ileocecectomy. Mean hospital stay was 10.5+/-1.0 days with adjusted hospital costs of $31,689+/-3018. We conclude that definitive treatment of advanced appendicitis can be performed by resection of the involved areas of the ileocecum. This can be accomplished with a primary anastomosis obviating the need for ileostomy and secondary operation. This aggressive surgical approach may reduce infectious complications and reduce hospital costs. PMID- 11768814 TI - Advanced age does not contribute to increased risks or poor outcome after major abdominal operations. AB - Elderly patients are still frequently denied major operations out of concerns over increased morbidity. The impact of advanced age on morbidity, mortality, and late outcomes after major gastric and pancreatic resections was studied by retrospective review with Chi square and regression analysis. Between July 1987 and June 2000, 179 patients underwent a major gastrectomy or pancreatectomy procedure at the City of Hope Cancer Center. There were 96 males and 83 females with a median age of 64 years (range 17-97) and elderly subsets more than 70 (n = 53) and more than 80 (n = 18) years of age. Diagnoses included gastric cancer (n = 83, 46%), pancreatic or periampullary cancer (n = 78, 44%), and benign pancreatic (n = 11, 6%) or gastric (n = 7, 4%) conditions. Age >70 years was correlated with more complex underlying medical conditions (P = 0.001) and gastrectomy for cancer (P = 0.01). None of four in-hospital deaths or 11 90-day lethal events occurred in patients >70 years of age (P = 0.005). Overall complications (35% vs 49%) and major complications (25% vs 37%) were less frequent in the older patient group [P = not significant (NS)]. Median intensive care unit stay (3 vs 2 days) and hospital stay (12 vs 12.5 days) were similar (P = NS). Pancreatoduodenectomy, gastrectomy for "benign" indications, and splenectomy--but not age--were significant prognostic variables for increased complications and longer hospital stay (at P < 0.05). At a median follow-up of 13 months (20 for survivors) the median survival after resection for gastric cancer (30 vs 16 months) or pancreatic/periampullary cancer (30 vs 23 months) was not inferior in elderly patients (P = NS). Five-year disease-free survival was superior in gastric cancer patients >70 years (59% vs 26%, P = 0.03) but not for pancreatic cancer. Advanced age under current clinical selection criteria does not impose increased hazards beyond disease- and procedure-related risk factors for patients undergoing gastrectomy or pancreatectomy; no patient should be denied these operations on the basis of age criteria alone. PMID- 11768815 TI - Reduced length of stay by implementation of a clinical pathway for bariatric surgery in an academic health care center. AB - Bariatric surgery is being performed in increasing numbers in an era when reimbursements are being reduced. Academic health centers bear the responsibility for training surgeons to perform these operations yet must keep costs to a minimum and retain high quality. The UCLA Bariatric Surgery Program developed a clinical pathway for the pre- and postoperative management for gastric bypass patients to achieve these goals. Medical records for 182 consecutive gastric bypass patients were retrospectively reviewed before implementation of the pathway (Group I) during the fiscal year of 1998/1999. Data on average length of stay, average intensive care unit length of stay, average standard variable cost, percentage readmission rate, and percentage return to the operating room were collected. This information was compared with the data collected prospectively from 182 patients after implementation of the pathway in July of 1999 (Group II) during the fiscal year of 1999/2000. Hospital cost per admission was reduced by 40 per cent in Group II compared with Group I (P < 0.02). The average length of stay was reduced from 4.05 days in Group I to 3.17 days in Group II (P < 0.033). Overall readmission rate was decreased from 4.2 per cent in Group I to 3.2 per cent in Group II (P < 0.05). There were no differences in morbidities between both groups. The pathway reduced costs by reducing the hospital length of stay, intensive care unit utilization, and readmission rates. Quality was maintained as evidenced by a similar pattern of postoperative morbidities yet readmission rates were reduced. Our results indicate that implementation of a clinical pathway for bariatric surgery reduces cost and improves quality of care in an academic institution. PMID- 11768816 TI - The effect of pleural adhesions on pediatric cystic fibrosis patients undergoing lung transplantation. AB - The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7+/-3.8 vs 10.6+/-5.6 years; P = 0.01) but had similar weights (34.8+/-8.7 vs 34.4+/-12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237+/-46 vs 219+/-39 minutes; P = 0.22) or cardiopulmonary bypass times (127+/-40 vs 133+/-49 minutes). Total perioperative blood requirements for the two groups were similar (35.6+/-14.9 vs 42.8+/-76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients. PMID- 11768817 TI - Nosocomial pneumonia is not prevented by protective contact isolation in the surgical intensive care unit. AB - Nosocomial pneumonia (NP) is the leading cause of death from hospital-acquired infection in intubated surgical intensive care unit (SICU) patients. To determine whether protective contact isolation would lower the incidence of NP in intubated patients we performed a prospective, randomized, and controlled study in two SICUs in a tertiary medical center. Over a period of 15 months two identical ten bed SICUs alternated for 3-month periods between protective contact isolation (isolation group) and standard "universal precautions" (control group). In the isolation group all personnel and visitors donned disposable gowns and nonsterile gloves before entering an intubated patient's room; handwashing was required before entry and on leaving the room. In the control group caregivers utilized only "standard precautions" including handwashing and nonsterile gloves for intubated patients. Respiratory cultures were obtained 48 hours after SICU admission and every 48 hours thereafter until extubation, transfer to floor care, or death. Airway colonization (AC) occurred in 72.7 per cent of isolated patients and 69.0 per cent of control patients (P = 0.61). The incidence of NP was significantly higher in the isolation group (36.4%) compared with the control group (19.5%) (P = 0.02). There was no statistically significant difference between groups in days from SICU admission to AC, days to NP, and mortality. We conclude that protective contact isolation with gowns, gloves, and handwashing is not superior to gloves and handwashing alone in the prevention of AC and NP in SICU patients and may in fact be detrimental. PMID- 11768818 TI - Intravenous interleukin-6 levels predict need for laparotomy in patients with bowel obstruction. AB - Interleukin-6 (IL-6) has been identified as a marker of ischemia. However, its association with bowel obstruction has not been studied. Fifty-seven patients diagnosed with bowel obstruction were evaluated in a prospective blinded study and managed either medically (n = 29) or surgically (n = 28) per decision of attending surgeon. Serum IL-6 levels were obtained at the time of diagnosis and serially during hospitalization. Mean IL-6 levels at the time of diagnosis were significantly higher in patients who required operation compared with medically treated patients (63.9 vs 19.6 pg/mL respectively; P = 0.027). Levels returned to those seen in medically treated patients 3 days after operation. There was no difference in temperature, white blood cell count, or lactic acid levels. Five patients required resection for ischemic bowel. Patients with ischemic bowel had significantly higher initial mean IL-6 (146.6 vs 45.9 pg/mL; P = 0.034) and lactic acid (23.6 vs 11.8 mg/dL; P = 0.035) at time of diagnosis compared with surgically treated patients without bowel ischemia. No difference in white blood cell count was seen. IL-6 was a sensitive predictor of patients with bowel obstruction requiring operation and for presence of ischemic bowel. IL-6 screening may allow for earlier and more selective operation potentially decreasing morbidity and mortality. PMID- 11768819 TI - The crura and crura-sphincter pressure dynamics in patients with isolated upright and isolated supine reflux. AB - The reason why patients with isolated supine reflux do not reflux in the upright position and patients with isolated upright reflux do not reflux in the supine position is unknown. Our objective was to determine the characteristics of the crura, lower esophageal sphincter, crura-sphincter dynamics, and esophageal body on manometry, endoscopy, and X-ray in patients with isolated upright and isolated supine reflux. Eighty consecutive patients with isolated upright reflux were compared with 82 consecutive patients with isolated supine reflux. Manometrically there was no difference in lower esophageal sphincter characteristics and esophageal contractions between the two groups. The prevalence of a hiatal hernia on manometry was similar between upright and supine refluxers (88% vs 88%). Upright refluxers had shorter hiatal hernias [median (interquartile range) 1.1 (0.65-1.8) vs 1.2 (1-2.3), P < 0.046)]. The median crural pressure, crura sphincter pressure gradient, and crura-sphincter pressure ratio in upright refluxers was 14.96 (9.5-21.27), 3.28 (1.7-12.2), and 1.33 (0.87-2.8) mm Hg, respectively. These values were significantly higher (P < 0.001) in supine refluxers at 21.43 (16.6-29.9), 10.66 (4.3-19.7), and 2.1 (1.3-4.2) mm Hg, respectively. We conclude that the significantly higher crural pressure in patients with supine reflux acts as a mechanical ring and as a physiologic protector against the unfolding of the sphincter in the postprandial and upright periods. Higher crura-sphincter pressure gradient and larger-size hiatal hernias in patients with supine reflux results in pressurization of the hernia sac and subsequent reflux when these patients are in a supine position. PMID- 11768820 TI - The topography of colorectal cancer varies by race/ethnicity and affects the utility of flexible sigmoidoscopy. AB - Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at "average" risk for the development of colorectal cancer either with flexible sigmoidoscopy and fecal occult blood testing (FOBT) or with colonoscopy. Patients who elect flexible sigmoidoscopy and FOBT undergo full colonoscopy only if left-sided neoplasia is detected or if the FOBT is positive. Unfortunately in blacks and whites most right-sided colorectal lesions are unaccompanied by left sided sentinel lesions, which leads some to prefer colonoscopic screening in these patients. The topography of colorectal cancer in Asians and Latinos is unavailable. We used 1988-1995 California Cancer Registry data to determine the topography of 105,906 consecutive colorectal cancers among Asian, black, Latino, and white patients. We found that the proportion of colorectal cancer distal to the splenic flexure and therefore detectable by flexible sigmoidoscopy varied by ethnicity: Asian (71%) > Latino (63%) > white (57%) > black (55%); P < 0.001. These differences were significant after adjusting for age and sex. The risk of distal disease relative to whites was 1.61 in Asians, 1.15 in Latinos, and 0.82 in blacks (P < 0.001). Flexible sigmoidoscopy detects a higher proportion of colorectal cancers in Asians and Latinos than in whites or blacks. Further study is needed to assess whether the topography of benign colorectal neoplasia parallels that of malignant disease. Colorectal screening recommendations may need to incorporate racial and ethnic differences in colorectal neoplasia topography. PMID- 11768821 TI - Asymptomatic renal neoplasms in the rectal cancer patient. AB - Although cancers of the rectum and kidney are common malignancies the incidence of coexistent rectal and renal primary tumors is unclear. Our objective was to determine the true incidence of synchronous neoplasms of the rectum and kidney. The computed tumor registry database at the City of Hope National Medical Center was queried for patients with synchronous rectal cancer and renal neoplasms presenting between August 1990 and August 2000. During the 10-year period there were 182 patients presenting for treatment of rectal carcinoma. Of these seven (3.8%) were found to have an asymptomatic renal neoplasm. Four patients underwent synchronous resection. Three patients underwent staged renal and rectal resections. The pathology of the renal lesions included renal cell carcinoma in six and an oncocytoma in one patient. Rectal lesions were all adenocarcinomas and all were within 10 cm of the dentate line. Three patients required abdominoperineal resections and four were treated with low anterior resections. Two patients presented with hepatic metastasis at the time of diagnosis. Five patients remain free of disease. Two patients died of persistent and recurrent disease 6 months and 40 months after operation. With the exception of one patient who required prolonged intubation because of severe Parkinson's disease there were no major complications after simultaneous resection of both renal and rectal disease. Simultaneous asymptomatic renal neoplasms may be found in up to 3.8 per cent of patients with rectal cancer. Synchronous lesions may be treated simultaneously without significant morbidity. PMID- 11768822 TI - Timing, safety, and efficacy of thoracoscopic evacuation of undrained post traumatic hemothorax. AB - Residual post-traumatic hemothorax (RPTH) occurs in 3 to 8 per cent of patients with tube thoracostomy and may cause serious infectious complications. Surgical evacuation is recommended, and thoracoscopic evacuation (THEVA) tends to replace open thoracotomy for this purpose. The objective of this study is to evaluate the optimal timing, safety, and efficacy of THEVA. Over 5 years patients with tube thoracostomy for trauma who had unresolved opacities on plain chest radiograph were evaluated by CT. If the residual fluid volume was estimated to be more than 500 mL3 on CT the patients were offered THEVA. Unstable patients were excluded. A score ranging from one (easy) to three (difficult) was used to grade the difficulty of the operation according to the attending surgeon's perception. Of 1728 chest trauma patients 143 (8%) were evaluated by CT for persistent opacity on plain film, 31 (1.8%) were found to have RPTH, and 24 (1.4%) were eventually taken for THEVA at 3.5+/-2 days after admission. Low oxygen saturation (less than 94%) was found in 58 per cent of patients before THEVA but in only 25 per cent after THEVA (P = 0.02). The majority of chest tubes (75%) were removed within 4 days of the operation. Two patients required conversion to thoracotomy. THEVA done within 3 days of admission was associated with a lower operative difficulty score, shorter hospital stay, and a trend toward shorter intraoperative time compared with THEVA done after 3 days of admission. All patients had effective resolution of their radiographic opacities after THEVA. Three patients developed a complication (urinary tract infection, pneumonia, and persistent air leak). We conclude that patients with significant RPTH and without major physiologic compromise are appropriate candidates for THEVA. The procedure is safe, evacuates PRTH effectively, and improves the respiratory function of affected patients. Ideally it should be performed within 3 days of admission. PMID- 11768823 TI - Mesh crural repair of large paraesophageal hiatal hernias. AB - Surgical repair is indicated in patients with paraesophageal hernias but is associated with a high recurrence rate. Our objective was to assess the safety and efficacy of mesh reinforcement of the crural closure in laparoscopic paraesophageal hernia repair. We conducted a 7-year retrospective review of all patients undergoing laparoscopic paraesophageal hernia repair with or without use of mesh. The main outcome measures were use of mesh, reason for use, age, sex, preoperative symptoms, length of operation, length of hospital stay, postoperative complications, and long-term follow-up conducted by physician interview. Twelve patients were repaired with mesh (Group A) and 12 without (Group B). Age, sex, operating time, length of hospital stay, and postoperative complications were similar in both groups. In Group A two patients required an interposition graft and ten required mesh reinforcement of the crural closure. One Group A patient developed an early recurrence requiring a reoperation, and one Group B patient developed a gastric leak where the fundus was sutured to the crura. The remainder of the patients experienced resolution of their symptoms at 2 weeks follow-up. Long-term follow-up (average 37 months) showed one Group B patient with a recurrence of reflux symptoms, but an upper gastrointestinal study showed no recurrence of hernia. All others remained asymptomatic. We conclude that the use of mesh in laparoscopic repair of large paraesophageal hernias appears safe and may reduce recurrence. PMID- 11768824 TI - Around-the-clock attending radiology coverage is essential to avoid mistakes in the care of trauma patients. AB - Financial constraints due to increasing operating cost and decreased reimbursement do not allow many hospitals to maintain coverage by attending radiologists around the clock (CARAC). Preliminary film readings by radiology trainees may be inaccurate. In trauma, decisions are made fast and are often based on these preliminary readings. To examine whether there are significant discrepancies between preliminary readings (PRs) and final readings (FRs) of CT scans of trauma patients we prospectively recorded PRs (done immediately by radiology residents) and FRs (done the following working day by radiology attendings) over a period of 6 months for trauma CT scans done between 5 PM and 7 AM on weekdays or weekends. A discrepancy was classified as significant if a change in management was instituted after FR. In 42 of 383 (11%) trauma patients there was a discrepancy between PR and FR. Patients with discrepancies had a higher Injury Severity Score, higher incidence of penetrating trauma, longer hospital stay, higher hospital charges, and higher mortality than patients without any discrepancy. Most of the discrepancies were found on abdominal CT scans. The lower the level of radiology resident doing the PR the higher the likelihood of a discrepancy. In 20 patients (5%) a significant discrepancy was found. We conclude that the absence of CARAC results in inaccurate FRs risking optimal trauma patient care. The institutional savings realized by avoiding CARAC may be offset by the cost of additional care provided to patients who have delayed diagnosis and treatment due to the lack of it. PMID- 11768825 TI - Laparoscopic ultrasonic epithelial ablation of the lower esophagus after nissen fundoplication in a porcine model: assessment of tissue damage and healing process. AB - A substantial population of patients with Barrett's esophagus has undergone antireflux surgery but still requires annual surveillance endoscopy. These patients would benefit from a definitive ablation of the Barrett's mucosa, which would remove the malignant potential of this disease. This study evaluates the efficacy of applying ultrasonic energy to remove the epithelium of the lower esophagus in a porcine model with prior Nissen fundoplication. Four Yakutan minipigs underwent laparoscopic Nissen fundoplication. After 2 weeks they underwent transgastric Cavitron ultrasonic surgical aspirator (CUSA; Valleylab, Boulder, CO) ablation of the lower esophageal epithelium. Healing of the mucosa was assessed by endoscopy at 2 weeks and pathological examination at 4 weeks after ablation. All pigs underwent successful laparoscopic Nissen fundoplication. Complete lower esophageal epithelial ablation was accomplished through the fundoplication in three animals. One pig developed a bezoar that prohibited ablation. At 2 weeks endoscopy showed patchy squamous epithelial regeneration, which was confirmed histologically. Esophageal specimens at 4 weeks showed complete regeneration of squamous epithelium with a partially healed small ulcer in one animal. No stricture formation was seen. We conclude that the CUSA technique can completely ablate Barrett's mucosa in the setting of a prior antireflux procedure. Healing with squamous mucosal regeneration is rapid and complete. PMID- 11768826 TI - Laparoscopic ultrasound with radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: technique and technical considerations. AB - The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure. PMID- 11768827 TI - Surgical diverticulitis: treatment options. AB - Acute diverticulitis requiring surgical intervention has conventionally been treated by resection with colostomy or delayed resection with primary anastomosis at a second admission. Our objective was to determine the outcome for treatment of diverticulitis with resection and primary anastomosis during the same hospitalization. We conducted a retrospective review of patients (n = 74) undergoing surgery for diverticulitis. Groups included: 1) resection with primary anastomosis (n = 33), 2) resection with colostomy followed by a takedown colostomy (n = 32), and 3) delayed resection with primary anastomosis at a second admission (n = 9). Despite local perforation primary anastomosis was often performed unless patients were clinically unstable or had fecal contamination. The operation was urgent in five (15%) patients in Group 1 as compared with 26 patients (88%) in Group 2. Serious intra-abdominal complications occurred in two patients (6%) in Group 1 as compared with nine patients (28%) in Group 2 and one patient (11%) in Group 3. Postoperative abscesses occurred in two patients in Group 1, five patients in Group 2, and one patient in Group 3. We have shown that resection with primary anastomosis for acute diverticulitis--even in selected patients requiring urgent operation--can be safely performed during the same hospital admission with a low complication rate. PMID- 11768828 TI - Reoperative coronary bypass surgery using normothermic cardiopulmonary bypass: comparison with first-time procedures. AB - Redo coronary artery bypass grafting (CABG) is characterized by increased patient risk compared with first-time CABG. The reason for higher risk is not completely understood but it is logically related to inadequate myocardial preservation evidenced by the higher incidence of postoperative low-output syndrome. We compared normothermic cardiopulmonary bypass with cold blood maintenance cardioplegia in both first-time and redo CABGs to determine whether this single approach is appropriate for both instances. Five hundred seventeen consecutive CABG patients were retrospectively reviewed. Four hundred fifty-four first-time CABG procedures were compared with 44 redo procedures. All aspects of the operation were identical including myocardial preservation. Retrospective univariant analysis of both groups followed. Three clinical features distinguished first-time versus redo CABG. These were previous percutaneous transluminal coronary angioplasty (first-time 19% vs redo 71%; P < 0.001), preoperative intra-aortic balloon pump (first-time 38% vs redo 71%; P < 0.001), and Parsonnet risk score (first-time 11.7+/-8.2 vs redo 19.2+/-8.8; P < 0.001). Operative mortality for redo CABG was higher than in first-time procedures (3.4% vs 6.4%; P = not significant), although small sample size limited statistical significance. The length of stay was statistically longer in redo patients (8.7+/ 10.8 vs 6.0+/-5.1 days; P < 0.01) and is related to a higher Parsonnet score, increased postoperative pneumonia, and failed percutaneous transluminal coronary angioplasty before redo CABG. We conclude that redo CABG is a different operation from first-time procedures and requires enhanced myocardial preservation. Normothermic cardiopulmonary bypass with cold blood maintenance cardioplegia does not appear to achieve this goal. PMID- 11768829 TI - Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure. AB - Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16 66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure. PMID- 11768830 TI - Use of OncoScint scan to assess resectability of hepatic metastases from colorectal cancer. AB - Patients with limited hepatic metastases from colorectal cancer can potentially be cured by resection. A number of patients deemed resectable by standard imaging procedures are found to have extrahepatic disease at laparotomy and are thus unresectable. A test capable of identifying these patients would assist in better patient selection. OncoScint (Cytogen Corp, Princeton, NJ) scan targets colorectal cancer by interacting with a tumor-associated glycoprotein. Can OncoScint scan be used to reliably identify patients with extrahepatic disease preoperatively? Between February 1996 and August 1998 eight patients with colorectal metastases to the liver were enrolled prospectively. All patients received preoperative OncoScint scan (indium-111) and underwent laparotomy. The laparotomy findings were correlated with the results of OncoScint scan. In four of eight patients (50%) OncoScint scan showed no extrahepatic disease. This was confirmed at laparotomy. All of these patients underwent hepatic resection. One of eight patients (12.5%) had OncoScint findings suggestive of extrahepatic disease pathologically confirmed during laparotomy. Three of eight patients (37.5%) had OncoScint findings of extrahepatic disease not confirmed by laparotomy. All three patients underwent hepatic resection. One of the three patients is still disease free for more than 48 months after hepatic resection. If OncoScint scan had been used to determine resectability this patient with false positive scan would have been denied a potentially curative operation. Because of the unacceptably high false positive rate the study was terminated after eight patients. Because of its high false positive rate (37.5%) OncoScint scan is not a reliable test for the assessment of extrahepatic disease. Other tests need to be developed to accurately stage extrahepatic disease with an acceptably low false positive rate to prevent exclusion of patients who can potentially be cured. PMID- 11768831 TI - The clinical utility of Tc-99m sestamibi scintimammography in detecting multicentric breast cancer. AB - The ability to recognize multicentric breast cancer preoperatively would assist in identifying appropriate candidates for breast conservation surgery. Tc-99m scintimammography (SMM) is an adjunct to conventional mammography in identifying selected patients with breast cancer. The purpose of this study is to report the utility of SMM in identifying patients with multicentric breast cancer. Breast cancer patients treated by mastectomy who underwent a preoperative SMM between 1992 and 1999 were identified using the institution's Tumor Registry. The pathology report of each patient was reviewed for multicentric disease defined as an additional focus of cancer within a different quadrant of the breast or greater than 2.5 cm from the dominant tumor mass. Each patient's preoperative SMM was reviewed and compared with the pathologic findings to obtain correlative data. Fifty-eight women treated by mastectomy had preoperative SMM (age range 35 78 years; median 52 years). Pathology revealed infiltrating ductal carcinoma in 49 patients (84.5%), infiltrating lobular carcinoma in five patients (8.6%), ductal carcinoma in situ in three patients (5.1%), and colloid carcinoma in one patient (1.7%). Multicentric disease was present in the specimens of eight patients for a prevalence of 10.3 per cent. SMM was positive for uptake in 36 of 58 patients (sensitivity 62.1%). The sensitivity, specificity, positive predictive value, and negative predictive value of SMM in the detection of multicentric disease were 62.5, 96, 71, and 94 per cent, respectively. Although the overall sensitivity of SMM in the detection of breast cancer is superior to that of conventional mammography and physical examination in identifying multicentric breast cancer it is not an accurate modality for detecting multicentric disease in this study group. However, it may have limited applications in specific cases. PMID- 11768832 TI - Radiation after mastectomy in high-risk patients: is it necessary? AB - A retrospective review of cases from 1988 through 1992 was performed examining high-risk breast cancer patients treated with modified radical mastectomy without postoperative radiation at a single institution. Locoregional recurrence, distant metastases, overall survival, and number of lymph nodes removed were examined. This was compared with recent Danish and Canadian studies. Thirty-three premenopausal node-positive breast cancer patients had a 9 per cent locoregional recurrence rate. In the Danish and Canadian studies the locoregional recurrence rates were 32 and 21 per cent. These were reduced to 9 per cent and 10 per cent respectively in the radiated arms. Our locoregional recurrence in nonradiated patients was similar to that in the radiated arms of the studies and improved when compared with recurrence in their non-radiated controls. The adequacy of the axillary lymph node dissection was examined. In the current study a median of 18 lymph nodes were recovered with only 3 per cent containing less than 12 nodes. In the Danish study a median of seven lymph nodes were removed. Similarly in the Canadian trial a median of 11 nodes were removed. With complete axillary dissection results equivalent to those of postoperative adjuvant radiation is achieved. Further randomized controlled studies with standard axillary dissections are needed before the recommendation of routine postoperative radiotherapy. PMID- 11768833 TI - Pelvic desmoid tumor: threat to mother and fetus. AB - Desmoid tumors (DTs) are well-recognized extracolonic manifestations of familial adenomatous polyposis. Surgical trauma and hormonal changes during pregnancy have been proposed as etiologic factors. We present a case of a rapidly growing pelvic DT arising from a J-pouch in a 27-year-old pregnant woman status postcolectomy with ileoanal J pouch anastomosis. The tumor interfered with the normal maturation and delivery of the fetus as well as the patient's ability to void or defecate prompting surgical intervention with resection of the tumor and adjacent J pouch at 23 weeks gestation. There are no other reports in the literature of pelvic DT requiring resection during pregnancy. Pelvic DTs in this scenario are potentially fatal to both mother and fetus secondary to uncontrolled bleeding. Surgical intervention should be limited to resection of tumor and when necessary the ileal pouch to minimize bleeding complications. PMID- 11768834 TI - A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus. AB - BACKGROUND: Pioglitazone is a member of a recently developed class of glucose lowering agents, the thiazolidinediones, used in the treatment of type 2 diabetes mellitus. In the United States, it is approved for use both as monotherapy and in combination with metformin, a sulfonylurea, or insulin; in Europe, it is approved for use in combination with metformin or a sulfonylurea but not insulin. OBJECTIVE: This article presents a systematic review of the published literature on the effectiveness of pioglitazone in the treatment of type 2 diabetes, both as monotherapy and in combination with other antidiabetic agents. METHODS: The peer reviewed English- and foreign-language literature was searched using MEDLINE, PubMED, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, the UK National Health Service Centre for Reviews and Dissemination databases, and the Office of Health Economics Health Economic Evaluations Database. Searches were not limited to specific publication types, study designs, dates, or languages. The latest search was performed in March 2001. For a trial to be included in the review, at least 1 outcome measure had to involve the effects of pioglitazone on glycemic control or cardiovascular risk factors, or its side effects. Because of the heterogeneity of studies, no formal meta-analysis was performed. RESULTS: Eleven studies met the inclusion criteria, 6 involving pioglitazone monotherapy and 5 involving combination therapy. Full reports were available for only 6 of the 11 studies. No studies directly compared pioglitazone with other antidiabetic drugs. Both as monotherapy and in combination therapy, pioglitazone produced decreases in blood glucose levels (up to 95 mg/dL) and glycosylated hemoglobin (up to 2.6%). At doses of > or = 30 mg/d, pioglitazone was associated with reductions in triglyceride levels (-30-70 mg/dL) and increases in high-density lipoprotein cholesterol (HDL-C) levels (-4-5 mg/dL). Pioglitazone treatment was associated with significant weight gain (up to 4 kg over 16 weeks). Adverse effects included mild edema (in up to 11.7% of patients) and a clinically nonsignificant decrease in hemoglobin concentrations. Abnormal results on liver function testing were no more common in treated patients than in control groups. CONCLUSIONS: Pioglitazone has been shown to reduce blood glucose levels in patients with type 2 diabetes. Although the observed decreases in triglyceride levels and increases in HDL-C levels could be expected to lead to a reduction in cardiovascular risk, the effects of weight gain may counteract this benefit. The evidence suggests that the preferred role for pioglitazone may be as an adjunct to metformin or a sulfonylurea in patients whose condition is not well controlled with monotherapy and for whom a metformin-sulfonylurea combination is contraindicated. There is a need for large-scale, long-term studies comparing the effectiveness of combination therapy that includes pioglitazone with that of other combinations of antidiabetic drugs. PMID- 11768835 TI - Current and emerging therapies for rheumatoid arthritis, with a focus on infliximab: clinical impact on joint damage and cost of care in canada. AB - BACKGROUND: Rheumatoid arthritis (RA) is a physically debilitating disease that places an enormous burden not only on individuals and their families but also on the economy. Affecting -1% of the Canadian population, RA is characterized by pain and swelling of joints. Without effective treatment, RA results in joint destruction that often requires surgery. OBJECTIVE: This review summarizes the effect of current and new RA treatments on joint damage, with a focus on infliximab. The health-economic repercussions and potential impact of arresting the joint destruction of RA are discussed. METHODS: Information for inclusion in this review was identified through searches of the MEDLINE and HealthStar databases from 1995 to 2000. Search terms included rheumatoid arthritis, treatment guidelines, economics, and individual drug names. RESULTS: Standard initial RA drug therapy has been aimed at reducing pain and inflammation, whereas use of the more potent disease-modifying antirheumatic drugs (DMARDs) has been reserved for later stages of disease. More aggressive RA treatment involves introducing DMARDs at the earliest stage. The largest single direct cost of RA involves hospital admissions for the correction of joint deformities. Among newer therapies, the anti-tumor necrosis factor-alpha agent infliximab has been shown to arrest radiographic measures of disease progression. CONCLUSIONS: With early and aggressive treatment involving new drugs and drug combinations, it may be possible to ameliorate the physical, social, and economic effects of RA. PMID- 11768836 TI - A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study. AB - BACKGROUND: The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice. OBJECTIVE: The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms. METHODS: This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D). RESULTS: A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028). CONCLUSIONS: The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability. PMID- 11768837 TI - Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults. AB - BACKGROUND: Placebo-controlled studies have indicated that both cisapride and metoclopramide promote gastric motility in critically ill patients. OBJECTIVE: This study was conducted to compare cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition (EN) and to evaluate the relationship between aspirated gastric residual volume and gastric emptying function in this patient population. METHODS: In this double blind study, critically ill, mechanically ventilated patients with an aspirated gastric residual volume > or = 150 mL while receiving intragastric EN were randomized to receive enteral cisapride 10 mg or metoclopramide 10 mg every 6 hours for a total of 7 doses. The acetaminophen-absorption method was used to assess gastric emptying at baseline and 30 minutes after the seventh dose by determining the area under the plasma concentration-time curve at 240 minutes (AUC240), maximum concentration (Cmax), and time to Cmax (Tmax). Gastric residual volume was measured every 6 hours before dosing. RESULTS: Fourteen patients were included in the study, 7 in each group. Patient characteristics were similar in the 2 groups. Compared with baseline, metoclopramide significantly accelerated Tmax (39.00 +/- 15.56 min with metoclopramide vs 103.71 +/- 47.35 min at baseline; P = 0.018) and increased Cmax (12.94 +/- 6.68 mg/L vs 6.97 +/- 4.78 mg/L; P = 0.018) and AUC240 (1,421.43 +/- 780.31 mg/L x min vs 839.00 +/- 545.58 mg/L x min; P = 0.043). Cisapride increased Cmax from baseline (12.27 +/- 8.95 mg/L vs 4.53 +/- 2.37 mg/L, respectively), but the difference was not statistically significant. Gastric residual volume was significantly reduced from baseline after 3 doses of metoclopramide (from 268.7 +/- 112.3 mL to 57.0 +/- 23.1 mL; P < 0.05) and was significantly lower after the seventh dose of metoclopramide than after the seventh dose of cisapride (5.3 +/- 8.2 mL vs 41.4 +/- 39.7 mL, respectively; P = 0.05). Cmax at baseline and residual volume at study entry were inversely correlated (r = -0.50; P = 0.049). CONCLUSIONS: Both cisapride and metoclopramide enhanced gastric motility and improved tolerance to intragastric EN. Metoclopramide reduced gastric residual volume to a significantly greater extent than did cisapride. Only Cmax at baseline was inversely associated with residual volume. PMID- 11768838 TI - Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. AB - BACKGROUND: The 5-hydroxytryptamine-receptor agonist almotriptan was found to be well tolerated and efficacious when administered orally in clinical trials of migraine treatment. OBJECTIVE: The primary objective of this study was to assess the efficacy and tolerability of 3 different doses of subcutaneous almotriptan in the treatment of acute migraine attacks. METHODS: This was a Phase II multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose finding study conducted over 7 months at 13 practice-oriented centers and 1 larger research-focused center. Patients experiencing moderate to severe migraine with or without aura, as defined by International Headache Society criteria, were randomly assigned to receive a single subcutaneous dose of almotriptan 2, 6, or 10 mg or placebo. The primary end point, pain relief at 2 hours, was self assessed on a 4-point scale (severe, moderate, mild, or no pain). Patients indicating mild or no pain were considered responders. The analysis was performed on an intent-to-treat basis. RESULTS: A total of 123 patients were enrolled (23 men, 100 women). Overall, almotriptan 6 and 10 mg were significantly more effective than placebo (P < 0.05, Fisher exact test). Response rates for the 6- and 10-mg doses were 96.5% and 90.3%, respectively, compared with 50.0% for placebo (P < 0.05, Fisher exact test). The proportion of patients with pain relief at 2 hours was not significantly different between almotriptan 2 mg and placebo. The response profile for the secondary end points was also better with almotriptan 6 and 10 mg than with placebo. Administration of almotriptan was well tolerated; the most frequently observed drug-associated adverse event was transient local irritation at the injection site. CONCLUSIONS: Almotriptan was well tolerated and significantly more effective than placebo in relieving moderate to severe migraine pain when administered as a single 6- or 10-mg subcutaneous dose. PMID- 11768839 TI - The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel. AB - BACKGROUND: Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. OBJECTIVE: This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). METHODS: This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. RESULTS: Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. CONCLUSION: In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel. PMID- 11768840 TI - Open-Label, parallel-group, multicenter, randomized study of cefprozil versus erythromycin in children with group A streptococcal pharyngitis/tonsillitis. AB - BACKGROUND: Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). OBJECTIVE: The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of pediatric pharyngitis/tonsillitis due to GABHS. METHODS: This trial compared the bacteriologic and clinical efficacy of erythromycin and cefprozil in children 2 to 12 years of age with culture-documented GABHS pharyngitis/ tonsillitis. Children who were allergic to penicillin, cefprozil, or erythromycin were excluded. Patients were prospectively randomly assigned to receive 10 days of oral therapy with either cefprozil suspension 15 mg/kg per day in 2 divided doses or erythromycin ethylsuccinate suspension 30 mg/kg per day in 3 divided doses. Primary efficacy end points were bacteriologic and clinical response 2 to 8 days after treatment ended. The frequency and severity of adverse events and their relationship to treatment were also assessed. RESULTS: A total of 199 patients were enrolled and treated (cefprozil, 99; erythromycin, 100); 12 patients in the cefprozil group and 15 in the erythromycin group were not evaluable. The GABHS eradication rate was significantly higher with cefprozil (95%) than with erythromycin (74%) (P = 0.001). The posttreatment carrier rate was lower in the cefprozil group (5%) than in the erythromycin group (18%) (95% CI, -22.3 to 3.8). Clinical cure rate was 90% (78/87) with cefprozil and 91% (77/85) with erythromycin (P = 0.95) (treatment group difference, -0.93; 95% CI, -9.9% to 8.0%). The overall incidence of drug-related adverse events was not significantly different in the 2 groups (11% with cef- prozil, 18% with erythromycin). The most common adverse events were diarrhea and vomiting. Two patients in the erythromycin group discontinued therapy because of adverse events. CONCLUSIONS: The bacteriologic eradication rate was significantly greater with cefprozil compared with erythromycin in children with pharyngitis/tonsillitis. Both cefprozil and erythromycin produced a clinical cure in >90% of patients. PMID- 11768841 TI - The peer-review process. PMID- 11768842 TI - Pharmacotherapies for attention-deficit/hyperactivity disorder: expected-cost analysis. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, hyperactivity, and impulsivity. Prevalence estimates in elementary school children generally range from 3% to 8%. ADHD is frequently treated with psychostimulant medications, which have been shown to improve both cognitive and behavioral outcomes for most children. OBJECTIVE: The goal of this study was to estimate the total expected costs for the treatment and management of school-age children with ADHD using 6 commonly prescribed pharmacotherapies: methylphenidate immediate-release/extended release (MPH IR/ER), methylphenidate immediate-release (MPH IR), Metadate CD (branded MPH IR/ER), Concerta (branded MPH ER), Ritalin (branded MPH IR), and Adderall (a combination of dextroamphetamine and amphetamine salts). METHODS: A literature review and clinical assessment using a 27-question survey instrument were used to capture information on the clinical characteristics of ADHD, including common treatment regimens, clinical management of patients, pathways of care, and components of care. A meta-analysis provided response rates for 3 commonly used pharmacotherapies: Metadate CD, MPH IR, and Adderall. Information from the clinical assessment and the meta-analysis were used to populate a decision-analytic model to compute total expected cost for each comparator. RESULTS: The average total annual expected cost per patient was $1,487 for Metadate CD, $1,631 for Concerta. $1,792 for MPH IR/ER, $1,845 for MPH IR, $2,080 for Ritalin, and $2,232 for Adderall. CONCLUSIONS: Metadate CD had the lowest total expected cost and Adderall had the highest total expected cost among the ADHD pharmacotherapies evaluated. The differences were attributable to differences in drug-acquisition costs and the need for in-school dosing of twice daily and thrice-daily medications. PMID- 11768843 TI - The World Health Report 2001. PMID- 11768844 TI - Parental 'affectionless control' in adolescent depressive disorder. AB - BACKGROUND: Adults with depressive disorder report high rates of sub-optimal maternal care in childhood. Despite the greater salience of relationships with parents earlier in life, associations with parenting style have not yet been systematically studied in adolescent onset disorder. METHODS: A six-wave, 3-year study of adolescent health in 2032 Australian secondary school students provided an opportunity to undertake a two-phase study of early onset depression. Between waves 2 to 6, a self-administered computerised form of the revised Clinical Interview Schedule (CIS-R) was used to generate a first phase diagnosis of ICD-10 depressive episode. Each subject with a CIS-R-defined depressive episode was selected for second phase assessment together with two subjects from the CIS-R non-cases in each school. Second phase assessment included a second diagnostic assessment using the depression and hypomania modules of the Composite International Diagnostic Interview (CIDI) and assessment of paternal and maternal style using the Parental Bonding Instrument. RESULTS: A total of 1947 out of 2032 subjects in the sampling frame (95.8%) participated in the cohort study (phase 1) at least once; 406 (94%) of the 435 selected subjects completed second phase assessment. One hundred and nineteen subjects fulfilled criteria for depressive episode on the CIS-R at one or more waves. Over the 30-month study period, 69 subjects (10 male, 59 female) fulfilled both CIS-R and CIDI definitions of depression at the same wave and were classified as 'definite depressive disorder'. Low maternal and paternal care held independent associations with both definitions of depression, with the effects clearest in those in the lowest quartile of reported care. After adjusting for low parental care, the associations between high parental control and depression were small. CONCLUSIONS: Sub-optimal parenting is associated with depressive disorder in adolescents. Low maternal and paternal care are each associated with a two- to three-fold higher rate of depressive disorder. These findings are consistent with an effect of sub-optimal parenting on the onset rather than course of disorder. Whether sub-optimal parenting is associated with a risk for the onset of depression outside the adolescent years has yet to be clarified. PMID- 11768845 TI - The proportion of veterans among homeless men: a decade later. AB - BACKGROUND: The purpose of this report is to evaluate the risk of homelessness among veterans as compared to non-veterans, and to ascertain whether the exceptionally high risk of homelessness among post-Vietnam era veterans first observed in 1987 was still evident one decade later. METHOD: Data from the 1996 National Survey of Homeless Assistance Providers and Clients and the 1996 Current Population Survey were used to examine the risks of homelessness among veteran men as compared to non-veteran men, stratified by age and race. RESULTS: The present results show that the cohort of veterans aged 20-34 that was most at risk in the 1980s, although no longer the youngest, still has the highest risk for homelessness. In 1996, the youngest cohort of veterans is also over-represented, but not to the extent found among young men 10 years before. Veterans over the age of 55 showed no increased risk of homelessness as compared to non-veterans. CONCLUSIONS: The observed cohort effect, which demonstrates an especially high risk of homelessness among veterans of the immediate post-Vietnam era, even as they age, may reflect the continuing influence of the early problems in recruiting for the All Volunteer Force (AVF). In contrast to the national draft, which promised a fair representation of the entire population of draft-eligible young men, the AVF also had the potential to attract young men with fewer alternative opportunities. PMID- 11768846 TI - Expressed emotion in staff-patient relationships: the professionals' and residents' perspectives. AB - BACKGROUND: Expressed emotion (EE) is a well-established, important predictor of the relapse rate of patients suffering from schizophrenia and other severe psychiatric disorders. EE measures the quality of the social interaction between a patient and his most important (in)formal caregiver. The aim of this study was to investigate the quality of the relationship in the staff-patient dyad as measured by the concept of EE. METHODS: EE was assessed using the Camberwell Family Interview (CFI, professionals) and the Perceived Criticism Scale (PCS, residents and professionals form) in a sample of 56 professional caregivers and their residents in nine sheltered living facilities in Flanders. RESULTS: Depending on the instrument, high EE was found to exist in one out of six (CFI) or one out of three (PCS) relationships. There was a significant positive correlation between the resident PCS and the critical comment scale of the CFI. CONCLUSIONS: The results of this study support the hypothesis that high levels of EE exist in some staff-resident relationships, which are mainly manifest as frequent critical comments and the presence of hostility. Emotional overinvolvement appears to be exceptional. Compared with the PCS, the CFI provides the most information about the quality of the relationship. PMID- 11768847 TI - The opinion of caregivers on aspects of schizophrenia and major affective disorders in a Nigerian setting. AB - BACKGROUND: In Nigeria the burden of caring for persons with severe mental disorders rests largely on families whose attitudes to these conditions have not been explored. OBJECTIVES: To assess the opinion of relatives of 75 schizophrenics and 20 major affective disorder cases on aspects of the disease and compare with the responses of relatives of cancer, infertility and sickle cell disease (SCD) cases. METHOD: Caregivers were assessed using a burden questionnaire that contained items on etiological beliefs and attitudes to illness. RESULTS: The responses of relatives of the two psychiatric illness groups were similar. The single most important etiological factors were that "it is Satan's work" (35.8%) and "it is a natural illness" (23.2%). Other factors were "genetic" (9.5%), "witchcraft" (10.5%) and "curse by enemies" (10.5%). This was similar to the opinion of cancer and infertility caregivers; but different from SCD where the most important causative factors were "genetic" (41.5%) and "natural" (21.5%). Psychiatric caregivers had higher frequency of anger and stigma. Over two-thirds of psychiatric caregivers felt glad caring for the patient and would not like the patient institutionalized. Most families were thought to be supportive and there was an impression that caring had made family emotional ties closer. CONCLUSIONS: These families were tolerant and would cooperate with health authorities. Causative models are influenced by available knowledge and practices in the culture. To actualize the potential of families to play useful community psychosocial roles, there is a need for public mental health literacy and welfare support. PMID- 11768848 TI - Accessibility and pathways to psychiatric care in a community-based mental health system. AB - BACKGROUND: The careful analysis of pathways to specialist mental health care, within the context of community-based services, is important because it allows a detailed understanding of the inter-relationship between the component parts of the whole system of care. Moreover, it permits a comparison of service functioning to made over time, and is one way to operationalise the measurement of accessibility to services. The aims of this study are to describe: (i) the pathways followed by patients with new episodes of care to community-based mental health services, (ii) the time intervals from onset of the problem to first contact with services, and then to onward referral to specialist care (accessibility), and (iii) to explore the short-term costs associated with different pathways. METHODS: Using data from the South-Verona Psychiatric Case Register, all new patients referred to any of the facilities which are part of the South-Verona Community Psychiatric Service (CPS) over a 6-month period (November 1999 - May 2000) were eligible to enter the study. Patients were interviewed by telephone using the Italian translation of the WHO Encounter Form. The costs of care provided in the 3 months following the index contact were assessed for all patients. RESULTS: The most common route to mental health services is via a GP (40%), followed by a referral from a hospital doctor (26%) and self-referral (23%). The median interval from onset to direct contact with the South-Verona CPS (12 weeks) was shorter than the intervals from onset to direct contact with other service providers (the median interval for contact with GPs and hospital doctors was 24 weeks). The intervals varied considerably from 1 week (for attempted suicide), to 1.5 years (for disturbed behaviour). The results of backward regression modelling revealed a significant relationship between patients' characteristics and community costs or total psychiatric costs (44% and 53% of the variance explained respectively). CONCLUSION: When the results are compared with a directly comparable earlier study in South-Verona, it is apparent that between 1991 and 1999 an increasing proportion of patients with insomnia and somatic disorders presented first to GPs, while a decreasing proportion of patients over the years sought care directly from specialist care. An increase in the role of local GPs as gatekeepers has, therefore, emerged. A prompt assessment by the South-Verona CPS of the patients' presenting problems was also confirmed, and this can be explained by the 'drop-in' approach at the Mental Health Centre, where patients can seek specialist care directly, without previously attending GPs. This method of measuring time intervals along pathways is proposed as a way to operationalise accessibility to services in future. PMID- 11768849 TI - Managing severe mental illness in the community using the Mental Health Act 1983: a comparison of Supervised Discharge and Guardianship in England. AB - BACKGROUND: Two measures in the English Mental Health Act allow requirements to be imposed upon patients living in the community. These are Guardianship (Section 7) and Supervised Discharge (Section 25A). AIMS: The paper aims to compare patients with mental illnesses, made subject to Guardianship or Supervised Discharge. METHOD: Data on patient characteristics, impairment, needs and interventions were collected from keyworkers in a random national sample of Trusts and local authorities. Ratings were obtained on standardised measures of disability, impairment and needs. RESULTS: Patients placed on Supervised Discharge were more likely to have problems of treatment compliance and drug misuse, whilst those on Guardianship were more likely to have problems of social welfare and higher ratings of disability and impairment. Supervised Discharge has a higher proportion of African-Caribbean patients. Interventions delivered are rated as effective for both measures. CONCLUSIONS: Legal changes proposed in England include a single power for supervision in the community. This should not mean a focus on risk management to the neglect of social welfare interventions. PMID- 11768850 TI - Threshold 3: the feasibility of the Threshold Assessment Grid (TAG) for routine assessment of the severity of mental health problems. AB - BACKGROUND: Evidence-based practice requires the development of measures which are suitable for everyday clinical use ('feasible'). There is no consensus as to how to establish feasibility. METHOD: The feasibility of a new assessment - the Threshold Assessment Grid (TAG) - for use when making referrals to mental health services was tested by training mental health teams in using the TAG and other standardised assessments, asking referrers to ten mental health services in London also to complete a TAG, surveying TAG users, and evaluating a feedback meeting at which TAG data were presented. RESULTS: One hundred and one (61%) mental health staff received training, and 445 (74%) referrers of 600 patients completed TAGs. Sixty-five (65%) questionnaires from TAG users were completed, and 24 (80%) people attending feedback meetings evaluated the TAG. These allowed the extent to which the TAG is brief, simple, relevant, acceptable, available and valuable to be investigated. CONCLUSION: The TAG exhibited good feasibility when used by mental health staff, and moderate feasibility when used by referrers. This approach can be used to investigate the feasibility of other standardised assessments. PMID- 11768851 TI - Fan effects reveal position-specific numerical concepts. AB - We examined associative interference (i.e., fan) effects to determine if the numerical concepts mediating numerical fact retrieval can be position specific. Participants memorized 15 "diamond arithmetic" facts (e.g., 3 [symbol: see text] 5 = 97; Whalen, 1997) involving five different operands. Ignoring operand position (i.e., left vs. right), each operand appeared equally often across items (i.e., position-independent fan was constant). In contrast, position-specific fan values varied across items (e.g., 2 appeared five times as the left operand, but once in the right position; 3 appeared four times as the left operand, and twice as the right operand, etc). Thus, we expect a fan effect only if the concepts activated by arithmetic operands are position specific. Results indicated that position-specific fan was an excellent predictor of trials to criterion, error rate, and latency. The concepts mediating number fact retrieval can be position specific. PMID- 11768852 TI - Multiplication by eye and by ear for Chinese-speaking and English-speaking adults. AB - English-speaking (n = 32) and Chinese-speaking adults (n = 32) solved single digit multiplication problems. In one condition, problems were presented as visual digits (e.g., 8 x 9). In the other condition, problems were presented as auditory number words in the participant's first language (e.g., /eit/ /taimz/ /nain/). Chinese-speaking adults made proportionately more operand-intrusion errors (e.g., 4 x 8 = 24) than English-speaking adults. Both groups made more operand-intrusion errors with auditory than with visual presentation. These findings are similar to those found when participants solve problems presented as visual number words (e.g., eight x nine), suggesting that in both cases the activation of phonological codes interferes with processing. PMID- 11768853 TI - Interactions between search mechanisms in conjunction search. AB - We report the results of a technique designed to measure interactions between different visual search processes. We interrupted pop-out search before it produced a detection response, by adding extra distractors to the display so that a target initially defined by a single feature difference (e.g., a yellow horizontal line among yellow vertical lines) could then only be found on the basis of the conjunction of two features (a yellow horizontal line among yellow vertical lines and pink horizontal lines; difficult search). This technique has been used to measure the duration of the perceptual components of pop-out search, independent of over-all response time, for targets presented among different sets of distractors. In addition, when pop-out failed because it was interrupted, past work has shown that it nevertheless provided useful information to the processes responsible for difficult search. That is, partial pop-out assisted difficult search, when extra distractors made search difficult because the target was between the two types of distractors in the relevant feature space (Olds, Cowan, & Jolicoeur, 2000a,b,c). The present results demonstrate that partial pop-out also assists difficult search when difficult search is a conjunction search, and therefore these interactions may occur at a stage where information from different feature dimensions is combined. PMID- 11768854 TI - Monocular unmasking of noise-embedded patterns. AB - Binocular disparity cues may help an observer "unmask" a target in a background, thereby enhancing its detectability (e.g., Moraglia & Schneider, 1992). Here, we sought to determine whether similar effects could be produced by monocular displacement cues resulting from a two-frame sequential presentation of a Gabor pattern (a sinusoidal modulation of luminance combined with a Gaussian modulation of local contrast) embedded in an unvarying field of two-dimensional Gaussian noise. The Gabor in the second frame was spatially displaced relative to its location in the first frame; the horizontal displacement corresponded to a phase shift of the peak spatial frequency of the Gabor of 0 degree, 90 degrees, 180 degrees, 360 degrees, or 540 degrees. Monocular detection thresholds for the Gabor were appreciably lower for the 90 degrees, 180 degrees, and 540 degrees shift, than for the 0 degree and 360 degrees values. We explain these findings in terms of a model that constitutes the monocular analog of our summation model of binocular unmasking. PMID- 11768855 TI - The accuracy of reaching movements in brief delay conditions. AB - We tested the hypothesis that a highly accurate target representation is available to the visuomotor system in brief (< 2 s) delay conditions. Participants reached to single midsagittal targets (20, 25, 30, 35, 40 cm amplitude) in full vision, open-loop and delay conditions (500, 1,000, 1,500 or 2,000 ms). Radial endpoint error was significantly greater for open-loop than full vision reaches, and was greater still for all delay conditions, which did not differ from one another. Radial error was greater for farther targets, although this tended to hold only for delayed reaches. These data suggest that the visuomotor system switches from on-line visual information to a degraded, stored representation very soon (< 500 ms) if not immediately after target occlusion. PMID- 11768856 TI - [Change in effects of motor preparation due to priming as a function of the amount of practice]. AB - The goal of the present experiment is to assess the effects of motor preparation on reaction time (RT) as a function of practice. We used a priming procedure to induce different levels of motor preparation. In reaction to a visual signal, the 16 participants had to respond with a flexion or an extension of the right or left wrist. Each participant performed 6120 successful trials divided into 34 experimental series. The first analysis of RT as a function of the type of cue (valid, neutral, or invalid) suggested that the time needed (a) to inhibit the prepared response and (b) to program the required one, remains stable throughout practice. A second analysis on the amount of information to be processed according to type of cue (0.42, 2.00, and 3.58 bits) indicated that central processing speed did not vary with practice. Indeed, only RT for the 0 bit condition decreased during the first 720 trials, suggesting that only the peripheral processes were influenced in early learning. PMID- 11768857 TI - Modulation of the attentional blink by differential resource allocation. AB - When one masked target (T2) follows another (T1) in close temporal proximity, identification accuracy of the second target is reduced for a period referred to as the attentional blink. Analysis of the attentional blink literature suggests that increasing the difficulty of T1 processing increases the magnitude of the blink. In a previous study that eliminated several untoward features of the typical attentional blink design (e.g., task switching, location switching, and stream contribution), we found no effect on blink magnitude when three levels of T1 difficulty (manipulated in a data-limited manner) were randomly intermixed. Here, when we repeated the previous study using a blocked manipulation of T1 difficulty, which is characteristic of the literature, a significant positive relation between T1 difficulty and blink magnitude was found. Resource allocation put in place to encode T1 in advance of a dual-target trial thus seems to be the critical factor in mediating this relation. PMID- 11768858 TI - The effect of height in the picture plane on the forward displacement of ascending and descending targets. AB - The effect of height in the picture plane on the remembered location of ascending or descending targets was examined. Consistent with previous research, memory was displaced forward in the direction of motion. The magnitude of forward displacement was larger for targets low in the picture plane than for targets high in the picture plane, and this was observed with ascending motion and with descending motion. This pattern is consistent with the hypothesis that memory for the location of ascending or descending targets is biased by the effects of implied gravitational attraction on the velocity of those targets, and some implications of such a bias for issues in mental representation are noted. PMID- 11768859 TI - Different combinations of ritonavir-indinavir. PMID- 11768860 TI - Searching for the right dose of ritonavir-saquinavir. PMID- 11768861 TI - Study finds HIV subtly damages vision. PMID- 11768862 TI - IL-12 may be useful for hepatitis C. PMID- 11768863 TI - Does efavirenz cause breast enlargement? PMID- 11768864 TI - Andractim for HAART-associated breast enlargement. PMID- 11768865 TI - Expanded access to tenofovir. PMID- 11768866 TI - New formulation of ddI approved in Canada--Videx EC. PMID- 11768867 TI - AIDS and lymphoma. PMID- 11768868 TI - Encouraging news on lymphoma from France. PMID- 11768869 TI - Chemo and HAART extend survival with lymphoma. PMID- 11768870 TI - Can low-dose shark cartilage make Kaposi's sarcoma disappear? PMID- 11768871 TI - Cidofovir for KS lesions. PMID- 11768872 TI - Looking at soluble CD23 levels to predict lymphoma. AB - As we noted in our first article on lymphoma, there isn't any quick and simple test to diagnose or predict which PHAs will develop this cancer. Nor are there any symptoms that specifically occur from having lymphoma. To try to remedy the situation, researchers in Italy have been monitoring levels of the a protein called soluble CD23 (sCD23) in the blood and fluid surrounding the brain- cerebrospinal fluid (CSF). They have found higher-than-normal levels of sCD23 in the CSF of PHAs who have brain lymphoma. PMID- 11768873 TI - The next big challenge: managing HIV infection in an age of higher resistance. PMID- 11768874 TI - Can advocates keep congress focused on HIV? PMID- 11768875 TI - Behavioral help brings safer sex practices. PMID- 11768876 TI - Community-based efforts chalk up successes. Sites in NC and Maryland have tale to tell. PMID- 11768877 TI - NC testing projects get to the heart of the problem. Nurses, health vans go to those most at risk. PMID- 11768878 TI - Maryland program focuses on HIV 'positives'. PMID- 11768879 TI - Tenofovir approved: broad indication. PMID- 11768880 TI - T-20 small program, CD4 < 50, will enroll November 27 at 3:00 P.M. PMID- 11768881 TI - Treatment news from recent conferences: finding Web reports. PMID- 11768883 TI - Africa: funding sought for epidemic control. PMID- 11768882 TI - Anthrax, bioterrorism fears stimulate immune, other research. PMID- 11768884 TI - Anchored to a tree. PMID- 11768885 TI - Transcultural nursing among migrant farm workers. PMID- 11768886 TI - Caring for children of other faiths. PMID- 11768887 TI - Limbs of hope. Restoring amputees in Sierra Leone. PMID- 11768888 TI - Listening & learning. Fostering health care in Bulgaria. PMID- 11768889 TI - A flash of insight. PMID- 11768890 TI - Building bridges with girls in crisis. PMID- 11768891 TI - Perils of a pro-life nurse. PMID- 11768892 TI - Joshua. A home health nurse's borrowed blessing. PMID- 11768893 TI - In his arms. Embracing homeless kids. PMID- 11768894 TI - [Childhood tuberculosis--a marker of the tuberculosis occurrence in Denmark]. PMID- 11768895 TI - [IAirborne contact allergens from ornamental plants]. PMID- 11768896 TI - [Subjective symptoms without objective findings--a challenge for theory and practice of general medicine]. AB - Most practitioners know patients who suffer from subjective symptoms, although the doctor cannot find any objective findings or causal explanations. The majority of patients with medically unexplained disorders are women. In this article, I challenge the idea that these disorders are really unexplainable and inaccessible to diagnosis, treatment, or therapy. I present some experiences and findings from the research project "Symptoms as a source of medical knowledge", where an objective is to develop strategies where the patient's symptom experiences can be used to enhance the doctor's understanding of apparently unexplained disorders, their origins and consequences. Applying the theoretical framework of "recognition" and "empowerment", I propose some strategies intended to help the practitioner to encounter these challenges in everyday clinical practice. PMID- 11768897 TI - [Catheter-guided thrombolysis in peripheral arterial occlusion]. AB - By catheter-directed, regional, intravascular thrombolysis a thrombus-dissolving enzyme is applied through a catheter placed at/in the occlusion. Non-fibrin specific (streptokinase or urokinase) and fibrin-specific agents (tissue plasminogen activators) are available. The large randomised trials (TOPAS and STILE) have serious selection bias, which makes generalisation difficult. Other studies have incomparable data and thus meta-analysis is impossible. Consequently, a recent consensus document cannot recommend an agent or principle of infusion. Thrombolysis of late, but transitory (< 14 days), occlusions seems beneficial but long-term results are lacking and recurrences are common. Exclusion of preoperative thrombolysis in late and longer lasting occlusions (> 14 days) is debatable, because of a potential thrombolysis-caused improved run off. Individual case selection is still needed, because thrombolysis is a promising, although experimental, treatment. PMID- 11768898 TI - [Tuberculosis among children in Denmark, 1990-1999]. AB - INTRODUCTION: During a century with a decreasing incidence of tuberculosis (TB) in Denmark, the last 15 years have seen an increase. We describe the epidemiology of TB in children in Denmark with the focus on the impact of immigration. MATERIALS AND METHODS: Data from the national TB surveillance of 1990-1999 were analysed. The variables were age, gender, nationality, TB location(s), and the results of microscopy and culture. RESULTS: Three hundred and forty-nine children below 15 years of age were found, representing 8% of all notified cases of TB. Of these, 268 children (78%) were immigrants. The number of children increased over time, as did the proportion of immigrants (p < 0.0001). The median age was four years in the native Danes and nine years in the immigrant children (p < 0.001). The mean annual incidence of TB in the children was 3.9 per 10(5); 45.8 per 10(5) in the immigrants and 0.92 per 10(5) in the native Danes. The incidence increased from 2.0 in 1990 to 5.3 per 10(5) in 1999. Forty-nine per cent of the immigrants were Somalis, 13% were Pakistanis. The mean annual TB incidence was 581 per 10(5) in Somalis and 78 per 10(5) in Pakistanis. The incidence increased with age in children from Pakistan and Somalia and decreased in native Danes. Seventy-seven per cent of native Danes and 65% of immigrants had pulmonary TB +/- other locations (p < 0.05). Sixty-seven per cent of immigrant children with extrapulmonary TB had TB in the glands, 9% had TB in the bones, and another 9% had TB in the digestive system, proportions that were 38% (p < 0.05), 8%, and 0%, respectively, in native Danes. DISCUSSION: Immigration has had an impact on the incidence of TB, as well as on the pattern of TB location in children in Denmark. The incidence was 48 times higher in immigrant than in native Danish children. PMID- 11768899 TI - [Tension-free hernioplasty with a plug and a patch. A prospective long-term study of 483 cases of inguinal or femoral hernia]. AB - INTRODUCTION: The aim of this study was to assess the introduction of mesh plug and patch for hernia repair. MATERIALS AND METHODS: A prospective study was carried out on 483 consecutive cases of inguinal or femoral hernia treated at a county hospital in the period November 1993 to April 1997. The final follow-up was done by questionnaire. RESULTS: The operation was performed as a day-in procedure in 59% of the patients, and 35% stayed in the ward overnight. Normal daily activities were resumed within three (2-7) days (median [interquartile range]), and the sick leave was 7 (4-14) days. There were few postoperative complications, and reoperation was done in two cases. The overall recurrence rate was 5%, and for primary hernias 4%. There were no recurrences after operation for femoral hernia. Chronic pain was reported in 17% of the patients, 12% felt pain only during strenuous exercise. The observation at time was 46 (36-56) months (median [interquartile range]). DISCUSSION: Patients operated on with the mesh plug and patch technique had a short hospital stay and a short convalescence. The recurrence rate was acceptable. PMID- 11768901 TI - [Incest and sexual abuse. A retrospective study of 285 persons referred to ambulatory treatment of the consequences of incest and sexual abuse]. AB - INTRODUCTION: The aim was to describe a cohort of 285 persons referred to the Department of Psychotherapy, Aarhus University Hospital. MATERIAL AND METHODS: A retrospective analysis was carried out of all consecutively referred persons, interviewed and assessed by the author over a six-year period, when treatment of the psychological consequences of sexual abuse was available. RESULTS: A total of 285 persons were referred from 1 January 1989 to 31 December 1995, with complaints of psychological and social consequences of previous sexual abuses. A written invitation to attend a one-hour interview was sent at least twice with information about the questions that would be raised. Only 145 (51%) came for the interview. Of these 141 were women and four were men with an average age of 33.5 years. The time elapse between the sexual abuse and referral was 11 to 23 years. The sexual abuse started most commonly at the age of 4-6 years and ended before the age of 15 years. Seventy-five percent of the sexual abuse occurred within the family and the commonest form was sexual touching (30%), whereas 20% were exposed to intercourse. Of the 145 persons suffering from sexual abuse, the police were informed in 12 cases, but only five cases went to court. DISCUSSION: This retrospective study looks at the pattern of sexual abuse and its consequences. Very few are referred to our National Health Service for treatment and only half of those referred turn up. Many years have passed since the sexual abuse ended and the psychological and social consequences have become so severe as to wish referral. The psychological consequences are a feeling of insecurity, anxiety, guilt, and shame and an inability to establish normal psychological relations with other persons. Many live alone without a job or an education. Treatment options seem mandatory. PMID- 11768900 TI - [Effect of long-term treatment with inhaled budesonide on adult height of children with asthma]. AB - INTRODUCTION: Short-term studies have shown that inhaled corticosteroids may retard the growth of children with asthma. The effect of long-term treatment on adult height is, however, uncertain. MATERIAL AND METHODS: We conducted a prospective study of children with asthma to examine the effect of long-term treatment with inhaled budesonide on adult height. We report on 211 children who have attained adult height: 142 asthmatic children treated with budesonide, 18 asthmatic control patients who have never received inhaled corticosteroids, and 51 healthy siblings of patients in the budesonide group, who also served as controls. RESULTS: The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment (range 3-13 years) at a mean daily dose of 412 micrograms (range 110-877 micrograms). The mean cumulative dose of budesonide was 1.35 g (range 0.41-3.99 g). The mean differences between the measured and target adult heights were +0.3 cm (95% confidence intervals: -0.6; +1.2 cm) for the children treated with budesonide, -0.2 cm (95% confidence intervals: -2.4; +2.1 cm) for the control children with asthma, and +0.9 cm (95% confidence intervals: -0.4; +2.2 cm) for the healthy siblings. The adult height depended significantly (p < 0.001) on the child's height before budesonide treatment. Although growth rates were significantly reduced during the first years of budesonide treatment, these changes were not significantly associated with adult height. DISCUSSIONS: Children with asthma who have received long-term treatment with inhaled budesonide attain normal adult height. PMID- 11768902 TI - [Acute myocardial infarction associated with a mild blunt thoracic trauma]. AB - A case of acute myocardial infarction associated with a mild blunt thoracic trauma in a 60-year-old woman with normal coronary angiography is described. The underlying potential pathophysiological mechanisms are discussed. Lastly, the clinical and practical consequences of the new consensus document for the redefinition of acute myocardial infarction are briefly commented on. PMID- 11768903 TI - [Body building aided by intramuscular injections of walnut oil]. AB - This case report describes a 26-year-old body builder who had practiced several months of intramuscular self-injection of walnut oil. Apparently this is a normal procedure amongst body-builders. Our patient complained of swelling and tenderness overlying an injection site. Injections of oil may cause foreign body reactions, leading to tumours named according to the injected material; e.g. paraffinoma, oleoma. Systemic distribution has been reported to result in pulmonary complications. PMID- 11768904 TI - [Inguinal arteriovenous fistula after hernia surgery]. AB - A 57-year-old man who 16 years earlier had been operated on for right-sided inguinal hernia and since had undergone reoperation four times for recurrent symptoms from the region, presented with an arteriovenous fistula originating from the right inguinal area, with varicose veins spreading towards the umbilicus. Angiography confirmed the diagnosis and the fistula was resected, after which the symptoms completely disappeared. PMID- 11768905 TI - [RS-232 and research. An underestimated combination]. PMID- 11768906 TI - [Paracetamol increases the risk of upper gastrointestinal hemorrhage and perforation]. PMID- 11768907 TI - [Cochrane report on mammographic screening]. PMID- 11768908 TI - [The Lancet supports Danish researchers against the breast cancer group. Mammographic screening causes a conflict within Cochrane]. PMID- 11768909 TI - [Peroral antibiotic treatment of children with pyelonephritis is not recommended]. PMID- 11768910 TI - [Pneumococcal vaccine is clinically effective]. PMID- 11768911 TI - [Neurogenic bladder disturbances--who is to treat and follow-up the patients?]. PMID- 11768912 TI - Testing pregnant women in Canada for HIV. How are we doing? PMID- 11768913 TI - Training for rural practice. Lessons from Australia. PMID- 11768914 TI - Aren't we all family physicians? PMID- 11768915 TI - The importance of prevention in health care. PMID- 11768916 TI - A dog's life. PMID- 11768917 TI - Update on perinatal HIV. AB - QUESTION: Many patients in my practice come from countries where HIV is endemic. Are there current figures on their risk of being infected during pregnancy? ANSWER: In Ottawa and Toronto, Ont, about half the pregnant women identified as HIV-positive were born in countries where HIV is endemic. If you suspect a woman has HIV or have other questions, call the Motherisk HIV-Healthline at 1-888-246 5840. Human immunovirus infection among pregnant women continues to be a serious public health concern. Most fetuses can be protected from contracting HIV if appropriate antiretroviral (ARV) therapy is instituted. PMID- 11768918 TI - Ophthaproblem. Keratoconus. PMID- 11768919 TI - Medicolegal file. Use of unconventional medication. PMID- 11768920 TI - Just the berries. Diagnosing Chlamydia trachomatis. PMID- 11768921 TI - Is acetylsalicylic acid plus dipyridamole superior to ASA alone for secondary prevention of stroke? PMID- 11768922 TI - Prevention and treatment of influenza A and B. PMID- 11768923 TI - Screening for HIV during pregnancy. Survey of physicians' practices. PMID- 11768924 TI - Vaccination practices of Quebec family physicians. Influenza vaccination status and professional practices for influenza vaccination. AB - OBJECTIVE: To assess influenza vaccination status and influenza vaccination practices of family physicians in Quebec. DESIGN: Mail survey of a random sample of 1000 family physicians. SETTING: Family practices in the province of Quebec. PARTICIPANTS: Of 1000 Quebec family physicians sent questionnaires, 550 responded. After excluding physicians who worked only in institutions, had no patients older than 65 years, or did clinical work less than 20% of the time, 379 respondents were eligible for the study. MAIN OUTCOME MEASURES: Vaccination status of family physicians in 1996 and professional practices based on six clinical and administrative activities pertaining to influenza vaccination. RESULTS: Prevalence of vaccination was 35.5% (95% confidence interval 30.8% to 40.4%) among responding physicians and was higher among those 60 years and older, those with a chronic condition, and those perceiving high peer pressure to get vaccinated. Most respondents frequently assessed the current influenza vaccination status of their patients, risk factors for influenza-related complications, and contraindications to the vaccine. They also frequently provided education about influenza and its vaccine, recommended vaccination, and administered the vaccine. Only a few reported assessing prior influenza vaccinations or recording vaccination status regularly. Finally, vaccinated physicians recommended the vaccine more frequently to their patients than unvaccinated physicians did. CONCLUSION: Promotion programs focusing on peer influence could increase vaccination of family physicians. This could in turn improve vaccination coverage of elderly patients. PMID- 11768925 TI - [Evaluation of medical web sites. Interobserver and intraobserver reliability of an evaluation tool]. AB - OBJECTIVE: To develop and test the reliability of a tool for rating websites that provide information on evidence-based medicine. DESIGN: For each site, 60% of the score was given for content (eight criteria) and 40% was given for organization and presentation (nine criteria). Five of 10 randomly selected sites met the inclusion criteria and were used by three observers to test the accuracy of the tool. Each site was rated twice by each observer, with a 3-week interval between ratings. SETTING: Laval University, Quebec city. PARTICIPANTS: Three observers. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (ICC) was used to rate the reliability of the tool. RESULTS: Average overall scores for the five sites were 40%, 79%, 83%, 88%, and 89%. All three observers rated the same two sites in fourth and fifth place and gave the top three ratings to the other three sites. The overall rating of the five sites by the three observers yielded an ICC of 0.93 to 0.97. An ICC of 0.87 was obtained for the two overall ratings conducted 3 weeks apart. CONCLUSION: This new tool offers excellent intraobserver and interobserver measurement reliability and is an excellent means of distinguishing between medical websites of varying quality. For best results, we recommend that the tool be used simultaneously by two observers and that differences be resolved by consensus. PMID- 11768926 TI - Location of family medicine graduates' practices. What factors influence Albertans' choices? AB - OBJECTIVE: To examine factors that influence family medicine graduates' choice of practice location. DESIGN: Cross-sectional, retrospective survey employing a self administered, mailed questionnaire. SETTING: Family medicine residency programs at the University of Alberta (U of A) and the University of Calgary (U of C) in Alberta. PARTICIPANTS: Graduates (n = 702) who completed the family medicine residency program at U of A or U of C between 1985 and 1995. MAIN OUTCOME MEASURES: Current practice location; 23 factors influencing current practice location; physicians' sex; community lived in until 18 years of age. RESULTS: Response rate was 63% (442 graduates completed the questionnaire). Overall, the most influential factors in attracting graduates to their current practice locations were spousal influence, type of practice, and proximity to extended family. Type of practice, income, community effort to recruit, medical need in the area, and loan repayments had a substantial influence on family physicians' decisions to practise in rural areas. Male physicians ranked type of practice, whereas female physicians ranked spousal influence, as having the most influence on choice of practice location. Significantly more female than male physicians identified working hours, familiarity with the medical community or resources, and availability of support facilities and personnel as having a moderate or major influence on their decisions. CONCLUSION: Differences between rural and metropolitan residents and between sexes affect family medicine graduates' choices of practice location. These differences should be taken into account in recruitment strategies. PMID- 11768927 TI - Solution-focused therapy. Counseling model for busy family physicians. AB - OBJECTIVE: To provide family doctors in busy office practices with a model for counseling compatible with patient-centred medicine, including the techniques, strategies, and questions necessary for implementation. QUALITY OF EVIDENCE: The MEDLINE database was searched from 1984 to 1999 using the terms psychotherapy in family practice, brief therapy in family practice, solution-focused therapy, and brief psychotherapy. A total of 170 relevant articles were identified; 75 abstracts were retrieved and a similar number of articles read. Additional resources included seminal books on solution-focused therapy (SFT), bibliographies of salient articles, participation in workshops on SFT, and observation of SFT counseling sessions taped by leaders in the field. MAIN MESSAGE: Solution-focused therapy's concentration on collaborative identification and amplification of patient strengths is the foundation upon which solutions to an array of problems are built. Solution-focused therapy offers simplicity, practicality, and relative ease of application. From the perspective of a new learner, MECSTAT provides a framework that facilitates development of skills. CONCLUSION: Solution-focused therapy recognizes that, even in the bleakest of circumstances, an emphasis on individual strength is empowering. In recognizing patients as experts in self-care, family physicians support and accentuate patient-driven change, and in so doing, are freed from the hopelessness and burnout that can accompany misplaced feelings of responsibility. PMID- 11768929 TI - If not the north, then what? PMID- 11768928 TI - Varicella zoster virus. Recent advances in management. AB - OBJECTIVE: To provide an update on strategies for managing varicella zoster virus (VZV) and for preventing and treating established postherpetic neuralgia (PHN). QUALITY OF EVIDENCE: Treatment guidelines are based on randomized clinical trials. Recommendations concerning other aspects of VZV management (e.g., vaccination) are based mainly on expert opinion. MAIN MESSAGE: Varicella and herpes zoster caused by VZV can give rise to serious morbidity and mortality and should be treated. For preventing chickenpox, safe and effective immunization is widely recommended. Treating varicella-exposed seronegative pregnant women requires special attention because the virus can harm expectant mothers, fetuses, and newborns. The antiviral drugs, acyclovir, valacyclovir, and famciclovir, have been approved for treating herpes zoster and have a role in reducing the duration of PHN. Established PHN can be managed with analgesics, tricyclic antidepressants, and other agents. CONCLUSION: Vaccination and antiviral and other systemic agents can substantially reduce the morbidity associated with VZV infection. PMID- 11768930 TI - Hypothesis: the research page. Residents and research: what does it take? PMID- 11768931 TI - Conducting a clinical practice audit. Fourteen steps to better patient care. PMID- 11768932 TI - Diagnosis of Helicobacter pylori infection--the search goes on. PMID- 11768933 TI - Morphological pattern of salivary gland tumours. AB - OBJECTIVE: To delineate the spectrum of salivary gland tumors in our setup. SETTING: The Aga Khan University Medical Centre, Karachi. METHOD: Tumors were analysed considering histological type, age and sex of the patients and anatomic location. The diagnosis of individual tumours was based on the 1991 World Health Organisation Classification. RESULTS: During the span of eight years (1991-1998), 379 cases of salivary gland tumours were diagnosed. Of these, 205 (65.7%) were male and 174 (34.3%) were female. The median age at the time of diagnosis was 35 years. The median age for patients with malignant lesions (44 years) was 12 years older than those with benign tumours (34 years). Overall, malignant tumours were seen more frequently in males, however benign tumours were distributed equally between the two sexes. The most common site was parotid gland (82.85%). Only five cases of minor salivary gland tumours were seen. The most frequently diagnosed benign salivary gland neoplasm was pleomorphic adenoma (84.5%), followed by Warthin's tumours (6.18%), Mucoepidermoid carcinoma was the most commonly encountered malignant lesion (56.9%), followed by adenoid cystic carcinoma (19.6%). CONCLUSION: Plemorphic adenoma was the most common benign salivary gland tumour and mucoepidermoid carcinoma was the most frequent malignant neoplasm. Parotid gland was the most common site of origin in both benign and malignant tumours. The overall relative frequency of salivary gland tumours in this series correlates with that reported in the international literature. PMID- 11768934 TI - A case notes analysis of hysterectomy performed for non-neoplastic indications at Liaquat National Hospital, Karachi. AB - OBJECTIVE: To determine the indications, associated morbidity, mortality and histopathological findings in women who underwent hysterectomy for non-neoplastic indications at Liaquat National Hospital Karachi. MATERIAL AND METHODS: This is a five year retrospective case note study of 143 women who underwent hysterectomy, excluding all those performed for benign or malignant pelvic neoplasms (excluding fibroids) and hysterectomy following childbirth for postpartum haemorrhage. RESULTS: Menorrhagia was the commonest indication for performing hysterectomy. The majority of the patients were in their forties; the commonest post operative complications were pyrexia, urinary tract and wound infections in 16% of the patients. There was no mortality associated with the procedure. The histopathology of the specimens revealed adenomyosis followed by leiomyoma to be the commonest pathology. CONCLUSION: It appears that adenomyosis is a common pathology in women from various ethnic and social backgrounds in Karachi, who are suffering from menorrhagia. Early diagnosis with high-resolution ultrasound is possible and hysterectomy may be offered earlier to these women, as they do not usually respond to medical treatment. PMID- 11768935 TI - Significance of thyrotrophin and thyroxine estimations in type 1 diabetes. AB - OBJECTIVE: To investigate whether estimation of thyrotrophin (TSH) and thyroxine (T4) is significant to assess the thyroid status of diabetic patients. MATERIALS AND METHODS: Fifty patients with type 1 diabetes (25 male and 25 female) aged 9 50 years were included. The mean duration of diabetes was 6.7 +/- 4.3 years. Clinically they were not suffering from any systemic disease or endocrine ailment. Twenty-six, age and sex matched, normal controls were also included. The TSH and and T4 were estimated in the sera of all the subjects using the commercially available ELISA kits. RESULTS: The mean +/- SD concentration of TSH was raised significantly (p < 0.001) in the patients as compared to the controls, whereas the T4 concentration was comparable. Furthermore, 30% diabetics showed significantly elevated TSH concentration than the controls. CONCLUSION: It is proposed that the estimation of TSH in the patients with type 1 diabetes may be useful in the early identification of thyroid dysfunction. PMID- 11768936 TI - Effectiveness of endoscopic and open surgical management in benign ureteral strictures. AB - OBJECTIVE: To assess the effectiveness of different treatment modalities for benign ureteric strictures. SETTING: Department of Urology, Al-Emiri Hospital, Kuwait. PATIENTS AND METHODS: Twenty four cases (19 unilateral and 5 bilateral) of ureteral strictures were reviewed. Retrograde endoscopic dilatation was tried, initially for all of the strictures. Technical failure was observed in 8/29 (27.5%) strictures. Three of them were negotiated through antegrade endoscopic dilatation, while in 5 of the strictures open surgical repair was required. Both the balloon and fascial dilator were used for endoscopic dilatation; ureteroneocystostomy with or without Boari's bladder flap were the procedures employed for open repair. RESULTS: Of the 29 strictures the majority were secondary to Bilharzial cystitis (66.6%). Twenty-four (82.7%) strictures underwent endoscopic manipulation and 5 (17.2%) had open repair. Among the 24 strictures that had endoscopic dilatation, 21 (87.5%) were managed in retrograde fashion while in 3 (12.5%) technical failures were due to the inability to canulate the strictured ureter with a guide wire in retrograde fashion. All these patients were treated successfully by antegrade stenting. Among 24 strictures that were initially managed with dilatation and stenting, recurrence was found in 9 (37.5%) patients. The group had open repair, no recurrence was found during the follow up. There was no serious intraoperative or postoperative complications of both the procedures. Patients were followed up with intravenous urography. CONCLUSION: Endoscopic dilatation is an effective treatment modality for partial benign ureteric strictures. However, open ureteroneocystostomy with or without Boari's flap or Psoas hitch should be reserved for complete or recurrent ureteric strictures. Bilharzial strictures are amenable to endoscopic dilation but recurrence rate is high and re-implantation is frequently required. PMID- 11768937 TI - Impact of socioeconomic conditions on perinatal mortality in Karachi. AB - OBJECTIVE: To study and compare the perinatal mortality (PNM) in hospitals located in various socio-economic areas of Karachi. DESIGN: A prospective review of all births was done from May 1996 to April 1997. Precoded proformas were provided to each hospital and the birth and details of each mother and baby delivered recorded. SETTING: All mothers and their newborn delivered during the time period mentioned. OUTCOME MEASURES: Comparison of PNM in hospitals located in various socio-economic areas of Karachi. RESULTS: A total of 4957 proformas were filled, 63.5% by doctors, 32% by LHVs, 2.9% by administrator and 2.3% by paramedics. Overall 92.3% mothers were housewives, less than 45% of the mothers received primary/secondary education; 42% mothers were of the age 21 to 25 years. More than 52.3% fathers were unskilled labourers. Only 27% mothers were booked while the rest were unbooked or came to deliver on walk in basis. Majority (62%) of the mothers had a > 37 week duration of pregnancy and 51% newborns were male and 49% female. Twenty three percent of the newborns weighed < 2500 grams, remaining weighed > 2500 grams but less than 4500 grams; 24.5% newborns died on day one of birth. The PNM per 1000 births in the high, middle and low socioeconomic hospital was 16.4 +/- 23.6, 24.9 +/- 51.20 and 80.4 +/- 177.78 respectively. A statistical significance (p < 0.0000) by the Chi-square for several proportions was seen between the high middle and low socioeconomic hospitals of Karachi. CONCLUSION: The present socioeconomic conditions will take some time to change. However, this study indicates that perinatal mortality rate may be changed by an improvement in antenatal care of the mother, hence the fetus. PMID- 11768938 TI - Impaired splenic function in systemic amyloidosis: diagnostic importance of peripheral blood film. PMID- 11768939 TI - Moving from concepts to study types approaches to classifying scientific inquiry. AB - There is no such concept as "the ideal research method". Most study types are understood and taught in a relative vacuum without appreciating their philosophical context. However, to achieve an optimal approach is more a matter of resolving the congruence between research purpose and method. Proper location of research methods within a theoretical framework is therefore important, otherwise the resulting over-simplification will eventually lead to inappropriate use of study types. Designing any type of study encompasses the process of identification, exploration and explanation, and utilizes concepts such as manipulation, sampling, replication and time dimensions. Medical research has borrowed study types both from Epidemiology and Social Sciences and practiced as observational and experimental inquiries, and we offer in the present review a framework within which these various types may be understood. PMID- 11768940 TI - Knowledge, attitudes and practices of general practitioners in Karachi District Central about tetanus immunization in adults. AB - OBJECTIVE: To assess the knowledge, attitude and practices of general practitioners regarding tetanus immunization in adults. SETTING: The study was conducted in District Central, Karachi. STUDY DESIGN: This was a Knowledge, Attitude and practices (KAP) survey. METHODS: From a list of 1050 general practitioners (GPs), 100 were selected through simple random sampling and interviewed through a written questionnaire. RESULTS: Only 25% general practitioners had adequate knowledge about pre-exposure and 13% both pre- and post-exposure tetanus immunization. All were ready to participate in any program to update their knowledge. Ninety seven percent were practicing only post exposure immunization. In unimmunized patients with history of road side/street injury, 55% started tetanus immunization with tetanus toxoid (TT) only, 43% with Anti Tetanus Serum/Tetanus Immunoglobin (ATS/TIG) and only 2% with both TT and ATS/TIG. Only 13% GPs advised their patients to complete three doses of tetanus toxoid after initial contact. CONCLUSION: As majority of GPs had poor knowledge and incorrect practices so interventions like seminars and display of immunization protocols in the clinics are recommended. PMID- 11768941 TI - Awareness about scabies among general medical practitioners (GPs) of Karachi, Pakistan. AB - OBJECTIVE: To investigate the awareness of general medical practitioners (GPs) about scabies and to evaluate the differences in awareness, if any, between general medical practitioners graduated recently (last 10 years) and more than 10 years practicing in Karachi, Pakistan. METHODS: A pre-tested questionnaire survey was conducted among 200 GPs through a cross-sectional study design and a descriptive analysis was performed. RESULTS: Present study showed that a substantial number of GPs have inadequate knowledge regarding causative organism of scabies. If responding correctly to 75% of questions asked, is taken as the criterion for satisfactory awareness, only 36% of GPs had a satisfactory level of awareness. There was no effect of increasing age or years of experience on the level of awareness. CONCLUSION: There is a general lack of knowledge regarding various aspects of scabies among GPs. Therefore, active intervention is required to improve their awareness. PMID- 11768942 TI - The skin we are in--knowledge and practices regarding skin cancer in pre-clinical medical students. AB - OBJECTIVE: To assess the level of knowledge about skin cancer in youth and to explore the influence of gender and system of education on their knowledge and practices. MATERIALS AND METHODS: A questionnaire-based study was conducted at The Aga Khan University Medical College (AKUMC), on Year 2 pre-clinical medical students. Descriptive analyses to examine the frequency distribution, chi-square test and factor analysis were applied using SPSS. RESULTS: Seventyone students participated in the study; 90% scored > 55% in the questions regarding knowledge of Malignant melanoma (MM), whereas in the questions assessing practice only 11% of the respondents scored > 52%. They were largely unaware that appearance of a new mole is a risk factor for MM (56% respondents incorrect) and that skin cancer is one of the most common cancers (54% respondents incorrect). 73% reported being sunburned at least once during childhood and 40% suffered sunburns at least once this summer, which points to the inadequacy of sun protection. The risk of MM may double if severe sunburns are experienced during childhood. Education system and gender did not affect the knowledge and practices. The popular sources of learning about skin cancer were magazines (52%) followed by television (42%). CONCLUSION: There is a need for epidemiological studies in Pakistani population regarding skin cancer. For preventing excessive solar exposure which leads to sunburns, we recommend interventions like a Pilot Program for photoprotection education and Sun Awareness Week to improve knowledge and sun protection behavior. PMID- 11768943 TI - Trisomy 16, cause of first trimester abortion. PMID- 11768944 TI - An audit of blood crossmatch ordering practices at the Aga Khan University Hospital: first step towards a maximum surgical blood ordering schedule (MSBOS). PMID- 11768945 TI - [Problems of chronic fatigue]. AB - The review covers some human pathologic conditions defined as chronic fatigue syndrome, caroshi, burnout. Concerning nonspecific manifestations, one could characterize these conditions as general overfatigue of human. The authors attempt to consider these conditions from the viewpoint of occupationally induced disorders. PMID- 11768946 TI - [Epidemiology of bronchial asthma in aluminum production workers]. AB - The article represents higher risk of bronchial asthma in workers engaged into aluminum production through electrolysis. Epidemiologic methods proved relationship between intensity of fluor compounds effects and prevalence of bronchial asthma among electrolysis workers. PMID- 11768947 TI - [Features of dermatoses development in workers contacting irritants and allergens]. AB - Occupational hazards are characterized by low intensity and combined effects depicted in signs of occupational diseases. Effects of facultative irritants on development and course of occupational skin allergies are studied through example of organic solvents. PMID- 11768948 TI - [Changes in blood serum liquid crystal structure under experimental silicosis]. AB - To study changes in liquid crystal structure of blood serum, the authors used intratracheal model of experimental silicosis in rats exposed to DQ12 quartz dust. Early stages of disease demonstrated changes in blood serum structurization, seen in polarized light. Morphology of those changes could serve as a characteristic of silicotic process intensity. PMID- 11768949 TI - [Hematologic and cytochemical effects in specialists working with radiolocalization and radio navigation means]. AB - Examination of workers servicing radio location, radio navigation and communication means proved electromagnetic radiofrequency waves to induce some peripheral blood changes: cytopenia, Hb decrease, lower RBC and WBC counts, increased RBC with basophilic granularity, WBC metabolism alteration (higher acid phosphatase and myeloperoxidase activity), disordered lymphocytes subunits (T helpers, T-suppressors) ratio and T- and B-cells numbers. PMID- 11768950 TI - [Approaches to evaluation of translocated pollution]. AB - The authors suggested criteria of translocated pollution: scale, intensity, jeopardy, with consideration of dissemination mechanism--aerodynamic, water migration, terminal. The article covers classification of translocated pollution. Using methodology of risk evaluation, the authors assessed additional morbidity cases due to translocated pollution. PMID- 11768951 TI - [Analysis of occupational morbidity causes among workers of Lipetsk region]. AB - Higher occupational morbidity is not invariably a negative factor, sometimes being an indicator of good diagnostics and registration of occupational diseases, aimed to realize constitutional right for compensation of health damage caused by hazardous work conditions. PMID- 11768952 TI - [Clinical and immunologic effect of likopid in complex therapy of occupational bronchial asthma]. AB - Use of immune modulators for occupational bronchial asthma is expedient pathogenetically. Therefore the authors evaluated efficiency of LICOPID made in Russia for treatment of occupational bronchial asthma caused by chemical hazards and complicated by infection. PMID- 11768953 TI - [Occupational medical concepts associated with lead extraction from secondary raw materials]. PMID- 11768954 TI - [Features of immune reactions in workers of modern aluminium production]. PMID- 11768955 TI - [Diagnostic value of 3EG5 mucine antigen in clinical approaches to occupational respiratory diseases]. PMID- 11768956 TI - [Exposure to 50 of heart rhythm in power plants personnel]. AB - The authors first revealed reliable decrease in general capacity and amplitude of electromagnetic waves in staffers subjected to occupational electromagnetic fields of 50 Hz--that proves increased risk of cardiovascular diseases dependent on vegetative matters. Present norms on electric and magnetic fields of 50 Hz should be justified and intensified. PMID- 11768957 TI - Rapid and reliable site-directed mutagenesis using Kunkel's approach. PMID- 11768958 TI - Phenotypic expression of polymerase chain reaction-generated random mutations in a foreign gene after its introduction into an Acinetobacter chromosome by natural transformation. PMID- 11768959 TI - Polymerase chain reaction-mediated mutagenesis in sequences resistant to homogeneous amplification. PMID- 11768960 TI - Polymerase chain reaction-based signature-tagged mutagenesis. PMID- 11768961 TI - High-throughput scanning mutagenesis by recombination polymerase chain reaction. PMID- 11768962 TI - In vitro scanning-saturation mutagenesis. PMID- 11768963 TI - Random transposon mutagenesis of large DNA molecules in Escherichia coli. PMID- 11768964 TI - Random chromosomal gene disruption using cassette mutagenesis. PMID- 11768965 TI - Transplacement mutagenesis. A recombination-based in situ mutagenesis protocol. PMID- 11768966 TI - Site-directed mutagenesis facilitated by DpnI selection on hemimethylated DNA. PMID- 11768967 TI - Preparation of transposon insertion lines and determination of insertion sites in Arabidopsis genome. PMID- 11768968 TI - Evolutionary molecular engineering by random elongation mutagenesis. PMID- 11768969 TI - Random mutagenesis for protein breeding. PMID- 11768970 TI - DNA shuffling and family shuffling for in vitro gene evolution. PMID- 11768971 TI - Mutagenic polymerase chain reaction of protein-coding genes for in vitro evolution. PMID- 11768972 TI - Multiple site-directed mutagenesis in vitro. PMID- 11768973 TI - Two-stage polymerase chain reaction protocol allowing introduction of multiple mutations, deletions, and insertions, using QuikChange site-directed mutagenesis. PMID- 11768974 TI - Efficient and accurate site-directed mutagenesis of large plasmids. PMID- 11768975 TI - Combining site-specific chemical modification with site-directed mutagenesis. Versatile strategy to move beyond structural limitations of 20 natural amino acids side chains in protein engineering. PMID- 11768976 TI - Site-directed mutagenesis mediated by a single polymerase chain reaction product. PMID- 11768977 TI - Site-directed mutagenesis using altered beta-lactamase specificity. PMID- 11768978 TI - Megaprimer method for polymerase chain reaction-mediated generation of specific mutations in DNA. PMID- 11768979 TI - Generation of epitope-tagged proteins by inverse polymerase chain reaction mutagenesis. PMID- 11768980 TI - Site-directed mutagenesis by polymerase chain reaction. PMID- 11768982 TI - Methods for the isolation and maintenance of murine embryonic stem cells. PMID- 11768983 TI - Differentiation of embryonic stem cells as a model to study gene function during the development of adipose cells. PMID- 11768981 TI - Generation of multiple site-specific mutations by polymerase chain reaction. PMID- 11768984 TI - Embryonic stem cell differentiation and the vascular lineage. PMID- 11768985 TI - Embryonic stem cells as a model to study cardiac, skeletal muscle, and vascular smooth muscle cell differentiation. PMID- 11768986 TI - Cardiomyocyte enrichment in differentiating ES cell cultures: strategies and applications. PMID- 11768987 TI - Embryonic stem cells as a model for the physiological analysis of the cardiovascular system. PMID- 11768988 TI - The use of a chemically defined media for the analyses of early development in ES cells and mouse embryos. PMID- 11768989 TI - Isolation of lineage-restricted neural precursors from cultured ES cells. PMID- 11768990 TI - Lineage selection for generation and amplification of neural precursor cells. PMID- 11768991 TI - Selective neural induction from ES cells by stromal cell-derived inducing activity and its potential therapeutic application in Parkinson's disease. PMID- 11768992 TI - Epidermal lineage. PMID- 11768993 TI - ES cell differentiation into the hair follicle lineage in vitro. PMID- 11768994 TI - Embryonic stem cells as a model for studying melanocyte development. PMID- 11768995 TI - Using progenitor cells and gene chips to define genetic pathways. PMID- 11768996 TI - Analysis of the cell cycle in mouse embryonic stem cells. PMID- 11768997 TI - ES cell-mediated conditional transgenesis. PMID- 11768998 TI - Switching on lineage tracers using site-specific recombination. PMID- 11768999 TI - From ES cells to mice: the gene trap approach. PMID- 11769000 TI - Functional genomics by gene-trapping in embryonic stem cells. PMID- 11769001 TI - Murine embryonic stem cells as a model for stress proteins and apoptosis during differentiation. PMID- 11769002 TI - Phage-displayed antibodies to detect cell markers. PMID- 11769003 TI - Gene transfer using targeted filamentous bacteriophage. PMID- 11769004 TI - Single-cell PCR methods for studying stem cells and progenitors. PMID- 11769005 TI - Nonradioactive labeling and detection of mRNAs hybridized onto nucleic acid cDNA arrays. PMID- 11769006 TI - Expression profiling using quantitative hybridization on macroarrays. PMID- 11769007 TI - Isolation of antigen-specific intracellular antibody fragments as single chain Fv for use in mammalian cells. PMID- 11769008 TI - Detection and visualization of protein interactions with protein fragment complementation assays. PMID- 11769009 TI - Effects of altered gene expression on ES cell differentiation. PMID- 11769010 TI - Direct selection of cDNAs by phage display. PMID- 11769011 TI - Screening for protein-protein interactions in the yeast two-hybrid system. PMID- 11769012 TI - Hypoxic gene regulation in differentiating ES cells. PMID- 11769013 TI - Regulation of gap junction protein (connexin) genes and function in differentiating ES cells. PMID- 11769014 TI - Embryonic stem cell differentiation as a model to study hematopoietic and endothelial cell development. PMID- 11769015 TI - Analysis of Bcr-Abl function using an in vitro embryonic stem cell differentiation system. PMID- 11769016 TI - Embryonic stem cells as a model for studying osteoclast lineage development. PMID- 11769017 TI - Fifty years of publication. PMID- 11769018 TI - Some notes on the history of rheumatic carditis. AB - The history of rheumatic heart disease is briefly surveyed. Mitral regurgitation was recognized as the dominant lesion in acute carditis in the 1830s. This diagnosis fell out of favour in the early twentieth century. Also valvular lesions were then considered to be less important than myocardial disease as a cause of symptoms in chronic rheumatic heart disease. Successful mitral valvotomies in 1948 corrected this view. Mitral stenosis takes years to develop after acute valvulitis. Studies from the rheumatic fever research unit at Taplow showed absence of cardiac dilatation in first attacks of rheumatic carditis, poor prognosis with pericardial effusions, changing murmurs recorded by phonocardiography and cardiac output studies that justified treatment by bed rest. The multicentre trial of cortisone, adrenocorticotrophic hormone (ACTH) and salicylates showed no differences in development of chronic valvular disease. There is need for a more specific test for rheumatic activity than the erythrocyte sedimentation rate (ESR). It is hoped that a test can be developed to identify the minority of children at risk from rheumatic fever after a streptococcal throat infection in order to target antibiotic use. The declining prevalence of rheumatic fever is confined to the more prosperous countries. It remains common in the developing world. Penicillin prophylaxis is the sole advance in therapy. Better socio-economic environments are needed to reduce prevalence. PMID- 11769019 TI - The legal and ethical issues related to the control of HIV. PMID- 11769020 TI - Research ethics committee: getting started. AB - Unanticipated questions arose when starting an institutional research ethics committee in Grenada. Research ethics committees are charged with the ethical review of research protocols. They serve to protect people who volunteer as research subjects from harm or wrong that may result from participating in research. The Caribbean has a rich history of medical research involving human subjects. There is a growing will in the region to establish effective and sustainable research ethics committees that adhere to international standards. This paper examines uncertainties and questions that arose in starting a research ethics committee in Grenada, and describes how uncertainties were resolved. The questions centre on which guidelines to follow, who to appoint as members, what procedures to follow, and how to train members. An additional question relates to the role of a Ministry of Health in founding a research ethics committee. Resolution of these uncertainties shows that ethical review of research can be both effective and sustainable in the Caribbean. PMID- 11769021 TI - Plastic bottles as spacers for a pressurized metered-dose inhaler: in vitro characteristics. AB - Homemade spacer devices are commonly used by children with asthma to improve aerosol deposition from pressurized metered dose inhalers (pMDI); however, the efficacy and efficiency of these devices are not fully characterized. We determined the quality of fine particle fraction (< 4.7 microns) and ultrafine particle fraction (< 3.3 microns) of three bottles (from 280 ml to 500 ml) commonly used as spacers in Trinidad and Tobago and compared their performance to the commercially available valved holding chamber (OpT) and pMDI. These data were obtained in vitro using a cascade impactor. All 3 bottles and the OpT were similar (p > 0.05) in reducing the amount of albuterol emitted as large particles (> 4.7 microns) to less than 10 micrograms. The different sized bottles (from 280 ml to 500 ml) produced identical quantities of albuterol in the fine particle and ultrafine particle ranges (p > 0.05). All of the sample bottle spacers emitted a higher amount (p < 0.002) of fine and ultrafine particles than the OpT and pMDI alone. The OpT resulted in a significantly higher fraction of fine particles (p < 0.05) and a greater quantity of drug (p < 0.05) in the ultrafine range as compared to the MDI only. The sizes of particles obtained from the bottle spacers are those that have a high probability of reaching the lower airway; however, the clinical relevance of these findings remains to be determined. PMID- 11769022 TI - Outcome of first contact schizophrenia in Jamaica. AB - Several previous studies have identified high incidence rates, high relapse rates and poor short-term outcome for schizophrenia in African-Caribbeans in the United Kingdom (UK). Studies in the Caribbean have found the incidence of schizophrenia to be within worldwide levels, and one-year outcome to be much lower than that reported for African Caribbean patients in the UK. First contact patients with schizophrenia identified prospectively by the Present Status Examination were followed prospectively for one year. The main outcome measures which were collected from case notes included: clinical status and medication usage at contact with clinical service, employment status, outpatient clinic compliance, relapse rate and in-patient hospital status, after 12 months. Three hundred and seventeen patients between ages 15 and 55 years who had made first contact with the psychiatric service in Jamaica in 1992 received a computer diagnostic programme for the present status examination (CATEGO) diagnosis of schizophrenia. The majority 197 (62%) were treated at home, and 120 (38%) were admitted to hospital for treatment. Two hundred and sixty-four (83%) were still being seen after one year. The relapse rate was 13% (41 patients), higher for admissions (24, 20%) than for those treated at home (17, 9%; p < 0.001). The relapse rate was higher for patients brought into care by the police and mental health officers (p < 0.005). One hundred and thirty-five (43%) were in gainful employment within the 12-month period of follow-up, contrasted with the 40% unemployment rate for the 2.4 million population of the island (chi square = 39.322, p < 0.001). There was a self-reported use of medication in 213 (67%) patients, with 142 (45%) on monthly intramuscular depot medication. The low relapse rates and good outcome measures after 12 months of first service contact with schizophrenia are related to high levels of gainful employment and good intramuscular medication compliance. The favourable short-term outcome in Jamaica does not correspond to the high relapse rate for this condition found in African Caribbeans in the UK. PMID- 11769023 TI - Single dose (direct observed) azithromycin therapy for Neisseria gonorrhoeae and Chlamydia trachomatis in STD clinic attenders with genital discharge in Trinidad and Tobago. AB - The purpose of this study was to determine the prevalence and to assess the efficacy of a single one gram oral dose of azithromycin under direct observed therapy of genital discharge due to Neisseria gonorrhoeae and Chlamydia trachomatis infections in STD clinic attenders in Trinidad and Tobago. All patients with genital discharge and their contacts were given one gram oral dose of azithromycin under direct supervision after collection of urethral and cervical swabs for N gonorrhoeae culture and smear and for C trachomatis antigen detection by ELISA. Clinical and microbiological evaluation was done on those who returned after 7-10 days for follow-up. Of the 735 patients who were enrolled in the study, 319 (43.4%) had N gonorrhoeae and 100 (13.6%) had C trachomatis. Only 151 (36%) of the 419 patients with a pathogenic isolate returned for clinical and microbiological assessment. The remaining 268 (64%) of the 419 patients were lost to follow-up. One hundred and forty-three patients (94.7%) had total abatement of signs and symptoms after taking azithromycin. One patient (0.65%), who had both N gonorrhoeae and C trachomatis, improved clinically with the drug. Seven patients (six with N gonorrhoeae and one with C trachomatis) failed to respond clinically to azithromycin. Microbiological eradication was achieved in 115 (100%) patients who had single infection with N gonorrhoeae and in 23 patients (96%) with C trachomatis infection. Of 12 patients with combined infections, N gonorrhoeae and C trachomatis were eradicated in 10 and 12 patients, respectively, after initial treatment. In two patients with combined infection, N gonorrhoeae continued to be isolated after treatment with azithromycin. A single one gram oral dose of azithromycin under direct supervision is useful in the treatment of uncomplicated genital infection with N gonorrhoeae and C trachomatis in STD clinic attenders in Trinidad. PMID- 11769024 TI - Sexually transmitted disease symptoms. A comparative analysis of male and female youth in Jamaica. AB - Data from Reproductive Health Survey 1997 were used to examine symptoms of sexually transmitted diseases (STD) and sex behaviour of adolescents and young adults in Jamaica. Overall, nine per cent of the sample reported symptoms of STD in the year prior to the survey. Rates of high-risk sexual behaviours were high with one-fifth of the sample reporting multiple sex partners in the last three months. Slightly more than half reported condom use at last coitus. Logistical regression analyses indicated that being older, having multiple sex partners, using condoms inconsistently with steady partners, and having cultural attitudes conducive to high-risk sexual activity were all associated with having symptoms of STD. These findings indicate that certain sub-populations are more likely to have symptoms of STD. STD prevention programmes should recognize the various risk groups at increased risk of STD and, ultimately, HIV. Interventions should be targeted to those who continue to have unprotected sex with multiple sex partners. In addition, cultural factors should be considered in the development of such prevention programmes. PMID- 11769025 TI - The impact of side effects on family planning use among female clients of the public health services in Jamaica. AB - A one-year longitudinal study was undertaken in Kingston, Jamaica, to examine (i) the experience of side effects among female contraceptive users, (ii) the role of side effects in method continuation, and (iii) counselling regarding side effects. The study consisted of 463 women who utilized public health centres in Kingston and were either new users of contraceptives or who were switching contraceptive methods. They were recruited over a two-month period in 1998 and followed up for one year. All follow-up, interviews were done at the women's homes and complete interviews were obtained for 323 women. Information was collected about socio-economic characteristics, contraceptive history, service factors, experience with method and length of use. Forty-eight per cent of the women experienced side effects with the method accepted on recruitment to the study. Common side effects were irregular bleeding no period, headaches, nausea/dizziness and weight gain/loss. These side effects occurred mainly among pill and injection users. The occurrence of side effects had a negative impact on continuation rates. Forty-seven per cent of the women stated that they had received counselling regarding side effects. The level and impact of side effects among family planning acceptors at public health centres in Jamaica is of significance to the family planning programme. Method options need to be widened and counselling needs to be improved to ensure that women fully understand the issue of side effects and make informed choices about contraception. PMID- 11769026 TI - Patterns of trauma injuries in rural versus urban Jamaica. AB - Trauma admissions to St Ann's Bay Hospital in rural Jamaica and The University Hospital of the West Indies (UHWI) in the capital city of Kingston are compared. Trauma accounted for 19% and 22% of surgical admissions to UHWI and the St Ann's Bay Hospital, respectively. Sixty-three per cent of trauma cases admitted to the St Ann's Bay Hospital and 56% to the UHWI were due to unintentional injuries (95% CI, -0.05, 0.19). The main cause of unintentional injuries at both hospitals was motor vehicle accidents, accounting for 43% and 37% at UHWI and St Ann's Bay Hospital respectively (95% CI, -0.04, 0.17). The prevalence of falls was significantly higher in St Ann's Bay Hospital compared with UHWI, 41% and 26% respectively (95% CI, 0.10, 0.21). Intentional injuries accounted for 37% of cases in St Ann's Bay Hospital and 44% at UHWI (95% CI, -0.20, 0.04). The prevalence of firearm injuries was significantly higher at the UHWI than in St Ann's Bay Hospital, 55% and 18% respectively (95% CI, -0.15, -0.05). There was no significant difference in age and injury severity scores in the two hospitals but patients remained in hospital significantly longer at UHWI. PMID- 11769027 TI - Soft tissue sarcomas: a ten-year analysis. AB - Malignant soft tissue tumours are uncommon and the diagnosis is often difficult to make. This study of fifty-nine cases represents a pathological perspective of our experience with these tumours over a 10-year period. Malignant fibrous histiocytoma was the most frequent diagnosis made (36%) and the majority of these occurred in the lower limbs. In 11 (19%) cases, the sarcomas could not be further classified along histogenetic lines. We consider some of the reasons for this and discuss these findings in the light of an increasing trend towards the use of smaller samples for diagnosis. PMID- 11769028 TI - Images and diagnoses. Craniopharyngioma. PMID- 11769029 TI - Images and diagnoses. Glanuloma annulare. PMID- 11769030 TI - Images and diagnoses. Autosomal recessive form of osteopetrosis. PMID- 11769031 TI - Spontaneous coronary artery dissection in a thirty-two-year-old woman. A case report and a review of the literature. AB - A case of spontaneous coronary artery dissection, an extremely rare condition, is reported in a thirty-two-year-old woman. The pathological and clinical features as well as the management of this condition are discussed. Recent postulates with regard to aetiology and pathogenesis are emphasized. PMID- 11769032 TI - Ovarian hyperstimulation syndrome associated with clomiphene citrate. AB - Ovarian hyperstimulation is a recognized complication of ovulation induction with gonadotrophins. The syndrome is becoming more common as the number of women undergoing in-vitro fertilization increases. It is rarely seen in conjunction with clomiphene citrate usage. This case report is of moderate to severe ovarian hyperstimulation in a patient who was treated with clomiphene citrate because of infertility secondary to anovulation. She presented with amenorrhoea for five weeks, lower abdominal pain and a positive urinary human chorionic gonadotrophin (hCG) test. Pelvic ultrasonography was suggestive of a possible ectopic pregnancy with a differential diagnosis of a ruptured ovarian cyst. Diagnostic laparoscopy was done followed by laparotomy. Oophorectomy was performed because the ovary was thought to be complex with solid areas. However, conservative management with avoidance of laparotomy is the recommendation in confirmed cases of ovarian hyperstimulation but this requires a high level of suspicion in patients who have ovulation induction. PMID- 11769033 TI - Management of hepatic cysts by percutaneous drainage and instillation of tetracycline hydrochloride. AB - This paper reports two cases of benign hepatic cysts successfully treated by the instillation of tetracycline hydrochloride. The patients presented with solitary large symptomatic hepatic cysts and underwent ultrasound guided needle aspiration followed by the instillation of tetracycline hydrochloride. The cyst size diminished without complication and the patients have remained symptom free. We review the treatment of this uncommon entity and propose that injection of tetracycline hydrochloride is an effective nonoperative treatment of symptomatic solitary hepatic cysts. PMID- 11769034 TI - Vaginitis emphysematosa associated with an abnormal Pap smear. AB - Vaginitis emphysematosa is an uncommon inflammatory condition that is aetiologically linked to trichomonal or gardnerella infection, and has been associated with immunosuppressive disorders. The disease does not have deleterious sequelae and resolves on treating the underlying infection. We describe a case in which the disease predominantly affected the cervix leading to an abnormal pap smear and colposcopic investigation. PMID- 11769035 TI - Granulomatous lobular mastitis. A case report and review of the literature. AB - Granulomatous lobular mastitis is a rare, benign, inflammatory breast condition of unknown aetiology that can clinically mimic breast cancer. Awareness of this condition is important, as the appropriate specimens must be taken to confirm the diagnosis and to rule out an infectious aetiology. While surgical excision has been the traditional therapeutic modality, the most appropriate therapy seems to involve the use of corticosteroids, even in the case of recurrence. PMID- 11769036 TI - Compartment syndrome of the thigh. A case report and review of the literature. AB - A case of compartment syndrome of the thigh following a gunshot injury that resulted in significant morbidity is presented. Early diagnosis of this uncommon condition requires a high index of suspicion in order to reduce morbidity and mortality. Timely diagnosis, emergency three-compartment decompression, prophylaxis against reperfusion syndrome and aggressive rehabilitation are necessary for a favourable outcome. PMID- 11769037 TI - Sleep apnoea. PMID- 11769038 TI - [Frequency of tobacco smoking in groups of patients with pulmonary diseases]. AB - The importance of active smoking on respiratory health has been demonstrated in both cross-sectional and longitudinal studies. There is a time lag of cca 20 yrs between initiation of smoking and the appearance of disease symptoms. PROBLEM: Data about tobacco smoking and duration of smoking are very important in patients with lung diseases. AIMS: To evaluate the frequency of smokers and duration in some groups of patients with lung diseases. Also to determinate Statistically Significant Difference (P < 0.01) in average duration of smoking and average number of cigarettes per day between the observed groups. PATIENTS AND METHODS: We analyzed a randomized clinical sample from 6 groups of patients according to lung diseases. In every group we analyzed percentage of smokers, age, the frequency of male and female smokers, average duration of smoking and average number of cigarettes per day. RESULTS: Some of the results shown in tables and graphs. CONCLUSIONS: The highest percentage of smokers was at the group of patients with Lung cancer, the longest average duration of smoking was in the group of smokers with COPD, the highest average number of smoked cigarettes was in the group of smokers with pulmonary embolism etc. PMID- 11769039 TI - Assessment of community mental health care in the Federation of Bosnia Hercegovina (FBH) after the 1992-95 war. AB - Bosnia-Hercegovina is in the process of reforming its health care system. One realises that this is a complex matter that will cost a great deal of time and effort. The findings suggest that the highest priority now is the development of the 'mental health strategic and action 'plan', which includes (as a component of the overall PHC strategy) legislation, financing mechanisms, a clear statute for the CMHCs and staff, and to define the relationship with other PHC services. In addition, it is recommended that the authorities should take a more decisive co ordinating and leading role. To this end, a special Mental Health Task Force assisted by a professional advisory group on mental health and/or professional consultants could be established. In order to realise a real cost-effective community-based care, it is inevitable to allocate enough funds to these primary mental health care services and initiatives such as sheltered living and family support initiatives (eventually to reallocate funds from expenditures on hospital based care). A mental health reform does not happen in a vacuum and therefore can not be accomplished without 'negotiating' with other sectors/ministries, e.g., Ministries of Finances, Social Affairs/Displaced Persons and Refugees, International Trade and Economy. A multi-sector approach is considered indispensable. Overall management of CMHCs should be strengthened. In addition, it is important that CMHCs exchange information and promote standardised protocols and procedures to enhance comparability and structured referral. The planned Management Information System is a good example, but should be implemented as soon as possible in all CMHCs. Other initiatives to improve professional networking might include (community mental health) newsletters, round table conferences, etc. Further skills training of CMHC staff and management might be difficult to define as long as it is not clear what practical skills are required. Technical Assistance to the (mental) health sector should primarily focus on the overall framework and policy. Training should be tailored to the actual needs and focus primarily on local capacity building via training of-trainers. Health prevention and promotion, i.e. information provision to the general public and community participation in terms of support for self-help groups and consumer groups, deserve more attention than it has received so far. PMID- 11769040 TI - [Computerized information system support in continuous quality improvement in hospital care]. AB - DRG (Diagnosis Related Groups) classification system requests much of medical and financial data from patients record. We also need comprehensive Clinical Information System with computer database to manage such system. In our research we were using HCFA (Health Care Financing Administration) and AN-DRG (Australian National-DRG) methodology for DRG classification. We also used ICD 10-Revision for diagnosis coding. We have chosen ORL Clinic for DRG classification because of two reasons: 1) They treat two basic types of patients medical and surgical and 2) They had pretty good sorted patients' records. Our base for DRG classification was 1997 year. During our research we found many deficiencies in patient records in both its parts: medical and financial. Since all records were processed and stored manually, financial data didn't exist. So we had to use other ways for direct and indirect costs allocation (for Prospective Payment System purpose). In 1998 we processed 680 patient records (treated in 1997), and made DRG classification putting all 680 patients' records into 183 DRG: 47 medical and 136 surgical. This is so called CASE-MIX of the ORL Clinic for year 1997. DRG classification we made at Tuzla ORL Clinic was identical with HCFA DRG classification system in 92%. PMID- 11769041 TI - [Gasless laparoscopy]. AB - Gasless laparoscopy is minimal invasive surgical procedure in combination with conventional abdominal surgical procedures. For installation surgical instruments are necessary two small (10 mm) noses in suprainguinal regions. In this regions the flexible 10 mm trokars are install. The patients precedence: the abort of instillation CO2 in abdominal cavity, the pain is significant less, the shoulders pain is significant less. Together with optic endoscopic increment the operation is precise and safely. Gasless laparoscopy is good at the price. Gasless laparoscopic procedure uses multiple surgical instruments. In conclusion gasless laparoscopy is advantageously than laparoscopy with CO2. PMID- 11769042 TI - [The first hospitals in Bosnia-Herzegovina]. AB - This year in Bosnia and Herzegovina we celebrate three great healthcare jubelees: hundred and thirty five years of Turkish military hospital (nowadays General hospital) in Sarajevo (founded in June 1866) and the First Property of a Muslim religious hospital in Sarajevo (founded in October 1866), and fifty five years of the Medical faculty of the University in Sarajevo (founded in November 1946). In the time of the Turk, and later also the Austria-Hungarian government in Bosnia and Herzegovina of this and another, later founded hospital, played very important role in the taking care and the treatment of inhabitants. The hospital have during its history experienced the organizational and the functional changes, exemplary to time and conditions in which they existed. The author gives the more comprehensive section of the work and the functioning of the first hospital institutions at the bottom of our State, and state the more significant names whose contribution with their qualitative work is observed. PMID- 11769043 TI - [Functional dependence of the size of the left kidney to the size of the right kidney and the opposite]. AB - In this study anatomical variations of shape, size and relation of the kidneys have been analyzed. It has been carried out on 33 pairs of the human adult kidneys of both sex, randomly chosen. It has determined size, width and thickness of the kidney. The kidneys are very variable organs in the size and in the shape. Reduced largeness of the kidney and enlarged kidney are forms of variations of size. Reduced largeness of the left kidney has been found in 18.18%, and enlarged one in 24.24%. Reduced largeness of the right kidney has been found in 24.24% and enlarged one in 21.21%. Two types of the shape were presented: fetal lobularness and lobarnes of the kidney. The shape of left kidney was variable in 39.39%, fetal lobularness was present in 33.33%, and lobarness in 6.06%. The shape of right kidney was variable in 30.30%, foetal lobularness was present in 27.27%, and lobarness in 3.03%. All parameters that determine the size of kidneys show statistically high positive correlation. It means that mutual functional dependence is present, what made it possible from the size of right kidney calculating the size of left kidney and opposite. PMID- 11769044 TI - [Ultrastructural stereologic parameters of epithelial cells of alveolar ducts in the pre-and postovulatory female breast]. AB - Stereological characteristics of ductular parenchyma epithelial cells are analysed ultrastructurally on 8 cases of normal breast tissue. Different physiological states have been compared and tahat pre- and postovulatory. Volume density (VV), surface density (SV) and specific surface density (SV/VV) of nuclei and epithelial cells cytoplasm have been stereologically examined and compared. Postovulatory, the volume density (VV) and surface density (SV) of nuclei as well as specific surface density (SV/VV) of epithelial cells cytoplasm are much less, while a volume density (VV) of epithelial cells cytoplasm is greater. PMID- 11769045 TI - [General outcome in critical limb ischemia in patients with arterial occlusive disease (AOD)]. AB - BACKGROUND: Recent vascular studies suggests that patients with arterial occlusive disease (AOD) and with elevated score of multiple risk factors (MRF), especially diabetes mellitus, have an increased prevalence of critical limb ischaemia, increased incidence of lower limb amputations, and an overall poor outcome of their AOD. The aim of this study is to evaluate an overall outcome of AOD, Fontaine stage III and IV, and to correlate their outcome with score of MRF. METHODS: We enrolled a group of 136 patients (99 males and 37 females), with an average of 63.7 yrs and SD 12.2 all with AOD, Fontaine stage III and IV. We divided pts in three groups--pts on medicament treatment--MT group, pts for lower limb amputation--AMP group, and pts for vascular surgery. According to their clinical stage we had group in Fontaine stage III (n-48), and Fontaine IV (n-88). We followed 9 clinical variables: age, gender, tobacco, arterial hypertension, diabetes mellitus, hyperlipidaemia, level of fibrinogen, coronary ischaemic disease and cerebrovascular disease. RESULTS: In MT group we had n-91 (66.9%) with MRF score of 3.42. In Fontaine stage III we had 37 pts with MRF score of 3.89, and in Fontaine stage IV we had 54 pts with MRF score of 3.37. In AMP group we had n-23 pts (16.9%) with MRF score of 3.39, and all pts were in F IV stage. In VH group we had n-22 pts (16.1%) with MRF score of 3.1. In VH group 50% of pts were in F IV stage. In overall group (n-136) we had a significant number of Fontaine IV stage pts, p < 0.01. CONCLUSIONS: We had a high risk group of patients, with mean MRF score of 3.42, 23 pts (16.9%) were referred for lower limb amputation, and 23 pts (16.9%) for vascular surgery. MRF score correlate with overall outcome of AOD, r = 0.72, p < 0.001. PMID- 11769046 TI - [Prevention of thromboembolism in endoprosthetic orthopedic surgery]. AB - The most common and dangerous operative complication after procedure hip joint replacement in orthopaedic surgery is plumonary embolysm. In our work we compare frequency of tromboembolic complications in group which was under suggested profilaxa and in other group with no such profilaxa. Importance of this work is not in a reducing of such complications but also in accepting of unique, wide excepted and scientific based protocol of postoperative tromboembolic profilaxa in ou country. PMID- 11769047 TI - [Surgical treatment of rupture of the coracoclavicular ligament and postoperative rehabilitation]. AB - The aim of this paper is to present the results of the operative treatment of the coracoclavicular ligament. According to Tossy, the injuries are classified into thre degrees. Younger patients and sportsmen (57) with the injury of the third degree were operated in the period from 1987-2000. The diagnostic methods were clinical examination and x-ray in the frontal and sagital plane. The patients were operated by Bosworth method. The operation technique which is described is slightly modified as it facilitates the surgeon's work and gives excellent post operative results. The immobilisation was not used in the post-operative treatment. During the first week after operation a patient does static isometric exercises using the muscles of shoulders and arms, breathing exercises and passive exercises of the arm up to pain limit. The screw was removed under the local anesthesia after minimum of 6 weeks. Upon the removal of the osteosynthetic material we applied kynetic, hydro, magnetic and electrotherapy. The results of the operation were estimated after 2.5 months. Taking into consideration the functions of coracoclavicular ligament (the regulation of angle between clavicle and shoulder-blade, the limitation of rotation and elevation of clavicle, the support in bearing arm weight, the relaxation of joint between clavicle and shoulder-blade and the lateral reinforcement of acromioclavicular joint) its complete reconstruction is very important, and with the appropriate fixation of clavicle and shoulder-blade, accompanied by physical therapy, makes the basis for good results after the operation. PMID- 11769048 TI - Reconstruction of oesophagus for oesophageal carcinoma. AB - This paper presents a prospective study of early and late results in 92 patients (64 men and 28 women, aver age 51.5 years), with reconstruction of oesophagus performed for oesophageal carcinoma after partial or total esophagectomy with logoregional lymphadenectomy. Ninety-two selected patients divided into five groups (belong to pTNM stage 0, I, IIa, IIb and partly III) were subjected to this investigations. The investigated five groups included two groups of patients with esophageal carcinoma who have had esophagetcomy, left colon reconstruction with gastric and oesophageal anastomosis 21 cases and 28 patients with esophagectomy, cervical colostomy and oesophagostomy (first-stage) and skin tube in the neck (second-stage). In the remain investigated three groups, after eosophagectomy, a gastric transposition (in retrosternal position). Chung's pyloromyotomy and oesophagogastrostomy (first-stage) and the skin tube in the neck (second-stage), were carried out in 18 patients. Gastric transposition in the right pleural cavity, Chung's pyloromyotomy and oesophagogastrostomy were performed in 12 patients. The incidence of leak in the group who have had oesophagocolostomy was in four patients and later on, the stenosis in three cases, while in oesophagogastrostomy group (in retrosternal position) leak occurred in three patients, but later on, there was no stenosis. In the oesophagogastrostomy group in the right pleural cavity, leaking occurred in two patients, without late stenosis. There was only one leak in both two-stage operated groups and no late stenosis. The results of this study indicated that the two-stage oesophageal operation gives the most satisfactory reconstruction of oesophagus. PMID- 11769049 TI - Postoperative pulmonary changes after laparoscopic cholecystectomy. AB - BACKGROUND: Pulmonary function tests on the day after open upper abdominal surgery and cholecystectomy show decreases of 40% to 60% compared with preoperative determinations. In this prospective, study, we evaluated the pulmonary function during and after laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: Thirty patients were evaluated with preoperative and postoperative spirometry, arterial blood gas determinations and chast radiographs to quantitate the magnitude of postoperative pulmonary changes after LC. Spirometry and chast radiographs were made before and 24 h after operation. Blood gas analye were performed preoperative, and 24 h after operation. RESULTS: Forced expiratory volume in 1 s (FEV: mean +/- SD values; preoperative: 3.12 +/- 0.78; postoperative: 2.33 +/- 0.80; P < 0.05), forced vital capacity (FVC; preoperative: 3.58 +/- 0.95; postoperative: 2.93 +/- 1.05; P < 0.05), peak expiratory flow (PEF; preoperative: 5.59 +/- 1.97; postoperative: 4.27 +/- 1.60; P < 0.05) and the midexpiratory phase of forced expiratory flow (FEF25-75; preoperative: 1.98 +/- 0.93; postoperative: 1.60 +/- 0.73; P < 0.05), were reduced 20-25% on average compared with preoperative values. Clinically important changes in arterial blodd gas values did not occur. Of 30 postoperative chest films, 9 showed the development of microatetelctasis. CONCLUSION: Improved pulmonary function after laparoscopic cholecystectomy may account for the observed reduced rate of pulmonary complication after laparoscopic cholecystectomy. PMID- 11769050 TI - [Neuroleptic malignant syndrome]. AB - Neuroleptic malignant syndrome is not so often in our practice. In this study, we presented interesting case report. PMID- 11769051 TI - [Clinico-epidemiologic aspects of pulmonary echinococcosis in western Herzegovina from 1969 to 1998]. AB - This research has included 111 pulmonary echinococcosis patients in the billy mountainous, more cattle raising region of Western Herzegovina. Since 1969, the prevalence of pulmonary echinococcosis, which was 27 (0.15%) at the time, has had a slow declining tendency after the application of various epidemiological preventive measures synchronized by the veterinarian and the medical services. It was not until 1998 the prevalence result fell down to 1 (0.01%). This study describes the therapy approach of surgery results with 82 patients who were operated on, as well as the prognosis of 29 other echinococcosis patients who rejected surgery but were regularly checked up. Apart form the progress in healing this disease, which is still found and presents a problem in the Mediterranean part of Herzegovina, because of its frequency and the difficulty in diagnostics; and particularly because of possible complications of this zoonosis. The possibility and the way of the albendazolom drug treatment have also been described here. PMID- 11769052 TI - Grady IDP founder, Angelle Vuchetich, receives Kappers award at annual meeting. PMID- 11769053 TI - Oral oversights. PMID- 11769055 TI - Black and white men together (BWMT) Atlanta & AIDS survival project join forces. PMID- 11769054 TI - LIFEbeat--the music industry fights AIDS. PMID- 11769056 TI - Gain, no pain? PMID- 11769057 TI - Getting hip to hep. PMID- 11769058 TI - Women are tired of relying on men to wear a condom! PMID- 11769059 TI - Demands and challenges. PMID- 11769060 TI - Getting prescription help. PMID- 11769061 TI - Participants glean knowledge at first Healthy Choices = Healthy Lives session. PMID- 11769062 TI - Considering work: a client-focused model for people with HIV. PMID- 11769063 TI - Group employment counseling for people with HIV. PMID- 11769064 TI - [Suicide]. AB - BRIEF HISTORY: The definition of suicide differs depending on the era, author or theory. Society's attitude has varied throughout history. When psychiatry appeared in the nineteenth century it medicalized the problem. First with Esquirol in 1838, followed by Delmas in 1932. Whereas Durkheim, with his theory of anomia in 1897, defended the sociological position presented in the form of a law: the percentage of suicides increases in inverse proportion to the social integration of the individual and one should not forget Halbwachs (1930) in this debate. Re-medicalization was mainly due to Deshaies in 1947, who dismissed the excessiveness of these two trends, while remaining open to them. According to his theory, "suicidal equivalences" should also be taken into account, even if the individual's death wish is subconscious. CONTRIBUTION OF THE PSYCHOANALYTICAL THEORY: This contribution is considerable and has gone through several stages. Currently, psychoanalysts accept the influence of extrinsic factors in suicidal behavior. This is the case, for example, for the pre-morbid states or the initiating factors, the importance of which are no longer denied and which favor regression and destruction of the personality and resulting in suicidal behavior. DOES A CLINICAL PROFILE EXIST?: Fifteen percent of depressive patients commit suicide. With regard to the act itself, it is far more dangerous and violent in the elderly than in young adults. The suicide rate of elderly people is 2-fold greater than that of the general population. Suicidal equivalents consist in letting oneself die, because of the loss in will to fight that characterizes the classical syndrome of this attitude. EPIDEMIOLOGICAL DATA: In France there are around 12,000 suicidal deaths per year among 150,000 suicide attempts, i.e., 1 attempt every 4 minutes and 1 suicide every 40 minutes. This corresponds to a raw mortality rate of 20 out of 100,000 inhabitants. However, epidemiologists consider that these figures are underestimated by around 20%. Since 1983, they exceed the mortality rate caused by road accidents (8,000/year in France). MISINTERPRETED DEPRESSION: Most suicides result from depression that was not recognized and treated as such. Clinical intuition is essential. It is the risk of suicide that renders the diagnosis of depression urgent. Retrospective surveys show that 50% of individuals having attempted suicide had consulted a doctor the month preceding their act. It is therefore important to organize the prevention of such risks. When depressive patients do not express any suicidal tendency, it is essential to raise the subject. In most cases, verbalization relieves the patients. However the eventual hospitalization of such patients should always be boum in mind. PMID- 11769065 TI - [Quality of life of lumbago patients cared for in a pain center]. AB - OBJECTIVE: To evaluate the quality of life of patients treated in a pain center. METHOD: Sixty eight patients were assessed during their first consultation, then 6, 12 and 18 months later, using a quality of life questionnaire "SQVP or Subjective Quality of Life Profile" validated in French populations and a panel of questionnaires for the monitoring of chronic pain, recommended by the ANAES (French Agency for Health Assessment). RESULTS: Results showed that: the patients' quality of life was clearly deteriorated (lowest quality in the data base--14,000 patients--with regard to the SQVP); the profile obtained (severe handicap) suggests that the lumbagos are part of a psychiatric context; the patients' quality of life clearly improves after 6 months' treatment, but the pain only stabilizes later. PMID- 11769066 TI - [Doping in sports. Cases reported to the Poison Control Center of Marseille from 1992 to 2000]. AB - OBJECTIVE: To study the doping substances used in sport and their toxicity. METHODS: Retrospective analysis from January 1992 to December 2000 of the cases of use of doping substances in sport reported by telephone to the anti-poison center in Marseilles. RESULTS: Fifty-one cases were reported concerning 48 men and 3 women with a mean age of 30, ranging from 10 to 55 years. Sixty-three percent of cases were reported over the last four years. The sport practiced was bodybuilding, except in 2 cases (cycling in one case and running in the other). The products used were mainly anabolizing hormones (15 times), clenbuterol (14 times) and creatine (7 times). A third of cases concerned associations of substances and 19 cases presented with symptomatology. CONCLUSION: The diversity in nature and status of the substances mentioned and their association requires enhanced vigilance with regard to the use of drugs in sport. The recent measures voted within the framework of the anti-doping law dated 23/3/99 are aimed at increasing surveillance with the development of anti-doping antennae. PMID- 11769067 TI - [Von Recklinghausen's disease associated with pancreatic somatostatinoma]. AB - INTRODUCTION: Pancreatic somatostatinoma is a rare entity and its association with Von Recklinghausen's disease has only been described on two occasions. We report a new observation, with clinical and evolving status differing from those described in isolated cases of somatostatinoma. OBSERVATION: A 28 year-old man presenting with familial Von Recklinghausen's disease, had suffered for 10 years from paroxysmic abdominal pain. He was hospitalized for intense pain. Imaging revealed a retroperineal tumoral formation. Following duodenopancreatectomy, somatostatinoma was diagnosed. Diffuse metastatic miliary was revealed and multiple glandular metastases. DISCUSSION: Other than the rarity of the morbid association (pancreatic somatostatinoma and Von Recklinghausen's disease) described, this case is particular in that the patient was very young, symptomatology was unapparent and tumoral evolution was minimal. PMID- 11769069 TI - [Migration of pancreatic cyto-steatonecrosis]. PMID- 11769068 TI - [Paretic rhabdomyolysis revealing leptospirosis]. PMID- 11769070 TI - [Epileptic crisis after antimalaria chemoprophylaxis with chloroquine]. PMID- 11769072 TI - [Endoscopic diagnosis and treatment of superficial bladder tumors]. PMID- 11769073 TI - [Assessment of loco-regional extension of superficial bladder tumors]. PMID- 11769071 TI - [Obsessive-compulsive disorder in children induced by streptococcal infection]. AB - FROM OBSESSIVE-COMPULSIVE DISORDER TO PANDAS: Obsessive-compulsive disorder (OCD) represents a potentially severe and handicapping disorder that affects several hundreds of thousands of children in France. OCD has, for many years, been considered as a neurosis resulting from mental conflicts. It is currently seen as a neurobiological disorder, the etiological substratum of which is more organic than mental. Recently a sub-type of OCD was isolated in children following infection by Group A b-hemolytic streptococci. This sub-type has been described as Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS). A NEW PHYSIOPATHOLOGICAL APPROACH: The putative dysimmune relationship between bacterial infection and neurotic disorder has led to the development of an original etiopathogenic model that may lead to new therapeutic strategies. The clinical case report of an adolescent presenting with trichotillomania associated with recurrent pharyngitis is a good illustration of this. PUBLISHED DATA: Data published in medical literature over the last 10 years indicates a 10% prevalence in the young suffering from OCD, i.e. 0.1 to 0.3% of the young population. PMID- 11769074 TI - [Endovesical chemotherapy for superficial bladder tumors]. PMID- 11769075 TI - [Endovesical immunotherapy: Calmette-Guerin bacillus]. PMID- 11769076 TI - [Photodynamic therapy for superficial bladder tumors]. PMID- 11769077 TI - [Cystectomy for superficial bladder tumors]. PMID- 11769078 TI - [Bladder diverticulum and superficial bladder tumors]. PMID- 11769079 TI - [Surveillance of superficial bladder tumors]. PMID- 11769080 TI - [Management of superficial bladder tumors]. PMID- 11769081 TI - [Survey on superficial bladder tumors with members of the French Association of Urology]. PMID- 11769082 TI - [Pathologic anatomy of superficial tumors of the bladder]. PMID- 11769083 TI - [Quality criteria in urinary cytology for tumor diagnosis]. PMID- 11769084 TI - [Fundamental bases of urothelial carcinogenesis]. PMID- 11769085 TI - [Etiologies of superficial bladder tumors]. PMID- 11769086 TI - [Descriptive epidemiology of superficial bladder tumors]. PMID- 11769087 TI - [Natural history of superficial bladder tumors]. PMID- 11769088 TI - [Diagnosis of superficial bladder tumors]. PMID- 11769089 TI - [Hyperici herba (Hypericum perforatum L]. AB - The aim of the author was to introduce the pharmacologically active compounds of Hyperici herba and their therapeutic effects. The extraction procedures and the possible interactions of Hypericum preparations with different drugs were also studied. PMID- 11769090 TI - [Analysis of antibiotic usage]. AB - Economic analysis is founded on the assumption that resources are limited and that should be used in a way that maximizes the benefits gained. Pharmacoeconomics extends these assumptions to drug treatment. Therefore, a full pharmacoeconomic analysis must consider two or more alternative treatments and should be founded on measurement of incremental cost, incremental efficacy, and the value of successful outcome. Antibiotic policy based only on administrative restrictions is failed, instead of it disease formularies and infectologist consultation system are needed. Equally important are various programmes that encourage the cost-conscious use of the antibiotics chosen. Some of the methods evaluated in the literature include: streamlining from combination therapy to a single agent, early switching from parenteral to oral therapy, initiating treatment with oral agents, administering parenteral antibiotic at home from outset of therapy, and antibiotic streamlining programmes that are partnered with infectious disease physicians. The solution is the rational and adequate use of antibiotics, based on the modern theory and practice of antibiotic policy and infection control, that cannot be carried out without the activities of experts in this field. PMID- 11769091 TI - [Liposomes as drug carrier systems. Preparation, classification and therapeutic advantages of liposomes]. AB - Bangham et al. (1965) created first the concept of the liposome as a microparticulate lipoidal vesicle separated from its aqueous environment by one or more lipid bilayers. Later Gregoriadis and Ryman (1972) suggested to use liposomes as drug carrier systems. Nowadays liposomes are under extensive investigation for improving the delivery of therapeutic agents, enzymes, vaccines and genetic materials. Liposomes offer an excellent opportunity to selective targeting of drugs which is expected to optimize the pharmacokinetical parameters, the pharmacological effect and to reduce the toxicity of the encapsulated drugs. To understand the system it is important to know the basic properties of these lipoidal vesicles. Our aim was to focus on the lipid composition and the method of liposome preparation what determine the liposomal membrane fluidity, permeability, vesicle size, charge density, steric hindrance and stability of the liposomes as principle factors those influence the fate of liposomes, their interactions with the blood components and other tissues after systemic administration or local use. PMID- 11769092 TI - [Lipase-catalyzed kinetic resolution of 2-substituted cycloalkanols]. AB - Racemates of cis- and trans-2-cyanocyclopentanol and -cyclohexanol, cis- and trans-2-dialkylaminomethylcyclopentanol, -cyclohexanol and -cycloheptanol and Boc protected cis- and trans-2-methylhydrazinocyclopentanol and -cyclohexanol were resolved through lipase PS (from Pseudomonas cepacia) or Novozym 435 (from Candida antarctica B)-catalysed asymmetric acylation. High enantioselectivity (E > 200) was observed when vinyl acetate was used as acylating agent, with diethyl ether or with diisopropyl ether as solvent. Reaction rates were markedly affected by the solvent and by the quantity of the enzyme. The size of the cycloalkane ring had a clear effect on the rate of enantioselective acylation: the acetylations of the five-membered cycloalcanols proceeded more rapidly than those of the six-membered ones and much more rapidly than those of the seven-membered systems. It can also be concluded that the trans isomers react more rapidly than the cis counterparts, the only exception being found in the case of 2 cyanocyclohexanols. In good correlation with the "Kazlauskas rule", in all cases, the (R) enantiomer is acylated faster than the (S) enantiomer, yielding an (R) ester and an (S) alcohol, which products from large-scale experiments were separated by column chromatography. During these studies, a total of 18 racemates of cis- and trans-2-substituted cycloalkanols were resolved by using lipases as catalysts, and 52 enantiomers (50 of them new) were characterized by NMR, elemental analysis and ocasionally MS. PMID- 11769093 TI - [Research on synthetic peptides of biological interest]. AB - Research on synthetic peptides at the Institute for Drug Research (IDR) is exemplified by an overview of the projects that resulted in significant results. The first synthesis of oxytocin, a pituitary hormone, in 1953 launched the research on synthetic peptides all over the world. This synthesis was reproduced by Bodanszky at the IDR in 1954, then, after some improvements, the process was presented to Richter to produce synthetic oxytocin for therapeutic purposes. Significant result was the first synthesis of the 39-member whole molecule of human ACTH, another pituitary hormone. A short SAR study on luteinizing hormone releasing hormone (LHRH) led to an interesting analog, Cit-8-LHRH, and somewhat later, to the D-Cit-6-LHRH analogues, of which SB-75 become marketed under the name Cetrorelix. Studies on the brain peptides, enkephalins, resulted in GYKI 14,238, the first analog that showed analgesic activity upon systemic administration and whose human efficacy could also be proven during clinical examination. Significant results were also achieved in the research on anticoagulant peptides. The first highly potent peptide aldehyde inhibitor of thrombin, GYKI-14,166, was identified at the IDR as well as its stable analog, GYKI-14,766. This compound was selected for detailed preclinical study, licensed to Eli Lilly Company, got the generic name efegatran, and entered clinical trials. The first non-covalent peptide inhibitor of thrombin, GYKI-14,525, was also identified at the IDR. Thus IDR really provided the prototype of original thrombin inhibitors in the mid 70's, and analogues were prepared in many laboratories through two decades. IDR's current research program's objective includes a quest for peptide originals that can inhibit both thrombin and factor Xa in solution and also within plasma clots in which these enzymes are entrapped. Structures with such inhibitory profile were identified among the efegatran related alpha-hydroxy acid and ethoxycarbonyl-amino acid derivatives. The follow up molecules are even more promising as antithrombotics, and may also be useful for treatment of disseminated intravascular coagulation, an often fatal syndrome, so we continue working on this project. PMID- 11769094 TI - [Discovery of the analgesic action of beta-endorphin: a subjective account]. AB - The contribution of the research workers of the Institute for Drug Research to some early discoveries in the field of endorphins is reviewed. The author takes pride in the fact the analgesic action of beta-endorphin was described in his laboratory concurrently with an American and a British group, respectively. The other main findings of his laboratory include demonstration of the cross tolerance between beta-endorphin and morphine, description of the elevation of the pain threshold upon inhibition of the breakdown endogenous opioids by intracerebroventricular administration of bacitracin, attenuation of morphine tolerance by alpha-MSH and Met-enkephalin, pharmacological development and clinical examination of a highly potent enkephalin analogue, (D-Met2,Pro5) enkephalinamide, coded as GYKI 14,238. PMID- 11769095 TI - [The search for anti-ulcer agents at IDR]. AB - 2-Pyridyl-thioacetamide (2-PTA) was synthesized at IDR in 1968. This molecule showed strong antiulcer/antisecretory effects in animals and man by inhibiting the proton pump. Based on our work Astra developed omeprazole which is the No. 1 drug in the world from 1996. 2-PTA remained a very popular template for drug design for a quarter of century. PMID- 11769096 TI - [Microbiological research for the Hungarian pharmaceutical industry]. AB - A survey is presented on the last 50 years of biotechnological R & D activities in the Institute for Drug Research, Budapest. In the 1950s and 1960s this Institute played an important role in the industry of antibiotics in Hungary, contributing to the development of manufacturing processes for streptomycin, oxytetracycline, neomycin and nystatine. In the late 1950s a microbial screening program was initiated, which led to the discovery of several new antibiotics and the isolation of microorganisms producing medically important, known antibiotics and other therapeutical agents of microbial origin from natural sources. In the 1970s and 1980s the biotechnological research group elaborated new industrial processes for the production of several antibacterial antibiotics, such as gentamycin C, sisomicin, tobramycin, apramycin, kanamycin B and mupirocin and the antitumor antibiotic daunomycin. In the last 15 years new processes have been developed for manufacturing the immunosuppressants cyclosporin A and mycophenolic acid and the hypocholesterolemic agents mevinolin and pravastatin as well as recombinant hirudin, a thrombin inhibitor. Research on steroid bioconversions has also been continued from the mid 1950s up to now. In the early 1960s manufacturing processes were developed for the anti-inflammatory prednisolone and the anabolic drug methandrostenolone. The results on microbial transformations (stereoselective reduction, hydroxylation) were utilized in the synthesis of contraceptive drugs. Since the mid 1960s several new microbial processes have been discovered for the selective side chain cleavage of natural sterols, resulting in various key intermediates for the synthesis of a wide variety of steroid drugs. PMID- 11769097 TI - [The search for anticancer agents at IDR]. AB - This paper deals with results of the search for anticancer agents achieved at IDR during the period of 1953-1983. This research activity concentrated on the following four topics: 1) biological alkylating agents, 2) nucleoside type antimetabolites, 3) anthracyclin antibiotics and 4) analogs of tamoxifen. Among those the first one was the most successful, resulting in five new cytostatics, which were marketed under the tradename Degranol [1,6-bis-(2-chloroethylamino) 1,6-dideoxy-D-mannitol], Mannogranol [1,6-dibromo-1,6-dideoxy-D-mannitol], Myelobromol [1,6-dibromo-1,6-dideoxy-galactitol], Zytostop [1,2,5,6-tetra-O methanesulfonyl-D-mannitol] and Lycurim [1,4-bis-(mesyloxiethylamino)-1,4-dideoxy eryhtritol]. PMID- 11769098 TI - [Cardiovascular system research at the Institute of Drug Research]. AB - The most significant achievements in the cardiovascular research areas have been reviewed. Among the beta-adrenoceptor blockers, antihypertensive, positive inotropic, and antiarrhythmic compounds synthesized and investigated at the IDR, a number of new drug candidates have been found and studied in clinical phases. One compound has been marketed (Tobanum, beta-adrenoceptor blocker). PMID- 11769099 TI - [History and major achievements of the Institute for Drug Research]. AB - The Institute for Drug Research (IDR) was established in 1950, as state-funded central research and development institution, with the aim of integrating the limited research capacity of post-war Hungary, and of providing products and technologies for the whole Hungarian pharmaceutical industry. Following various transformations, since October 1999 IDR has become a fully-owned subsidiary and major R&D institution of IVAX Corporation, headquartered in Miami, Florida. Early activities of IDR have focused on elaborating non-infringing technologies for the industrial production of pharmaceutical active ingredients of both synthetic and fermentation origin. By developing over 70 industrial technologies IDR has made significant contributions to the revitalization of the post-war Hungarian pharmaceutical industry. It has also played decisive role in the establishment and development of certain novel branches of this industry, e.g. fermentation production of antibiotics and steroids, peptide chemistry, steroid chemistry, etc. Original research targeting discovery and development of new chemical entities has become an integral part of IDR's activity since the mid-fifties. Of the several discoveries in various fields of biological activity 12 new drugs have become registered and marketed by Hungarian pharmaceutical companies. The industry-oriented R&D activity of IDR is hall-marked by the more than 800 patents field and registered during its history. Furthermore, over 2000 scientific communications and around 350 books, book-chapters and other scientific publications illustrate also its contribution to the domestic and international scientific community. PMID- 11769100 TI - [Highlights of CNS research at IDR: 2,3-benzodiazepines]. AB - 2,3-benzodiazepines (2,3-BDZs) synthesized and investigated at the Institute for Drug Research (IDR) represent a unique family among CNS active compounds. Though sharing common chemical backbone, 2,3-BDZs are pharmacologically different. Over the clinically non-sedative anxiolytic parent compound tofisopam, further derivatives with specific distribution of selective binding sites in the CNS have been found. Furthermore, dopamine-uptake inhibitors with stimulant character were also described. Finally but most importantly compounds with unusually broad anticonvulsant spectrum were also discovered. From this latter series the first non-competitive AMPA antagonist, GYKI-52,466 serves today as the golden standard for investigating the glutamate neurotransmission and the therapeutical potential of glutamate antagonists. The present paper summarizes the main pharmacological actions of the most prominent members of the 2,3-BDZ family. PMID- 11769101 TI - [Research on new AMPA antagonists of the 2,3-benzodiazepine type]. AB - This article is a written version of a lecture held at the 50th anniversary of the foundation of Institute for Drug Research. It describes the chain of ideas as well as the most interesting studies made during our structure-activity relationship investigations with AMPA antagonists of 2,3-benzodiazepine type, which led to the discovery of several new types of active non competitive AMPA antagonists. One proprietary molecule (GYKI-47261) exerts a broad spectrum of anticonvulsive and excellent neuroprotective effects and is going to be developed. PMID- 11769102 TI - [The fight against bacteria: the antibiotics policy]. AB - Development of bacterial resistance towards antibiotics is no longer a local phenomenon. It has by now become a European and global problem, as a result of unjustified and unprofessional administration of antibiotics in gratuitously high quantities, not only in the medicinal practice, but also in the agriculture. The resistant bacteria may spread from animals to humans, transmitted by the food chain. A recent danger includes the appearance of the vancomycin-resistant strains (VRSA) besides the methycillin-resistant Staphylococcus aureus (MRSA) infections. The number of the vancomycin-resistant Enterococci (VRE) is also expected to grow in the future. The present paper reports the results of the international activities in the past decades, which is related to the fight against resistant bacteria. Such research involves the production of synthetic compounds, the development of semi-synthetic beta-lactam-, aminocyclitol-, macrolide-, and glycopeptide antibiotics, as well as the introduction of new enzyme-inhibitory substances. Elaboration of basic principles of the rational application of antimicrobial agents is an increasingly urgent need along with the establishment of national and European data bases in which the supply and consumption of related medicines are registered and kept under control. PMID- 11769103 TI - [Quo vadis, Pharmacopoeia Hungarica?]. AB - The authors give an overview on the present role of the 7th Edition of the Hungarian Pharmacopoeia in the assurance of the good quality of medicines in Hungary. The reasons for the more and more limited applicability of the pharmacopoeia conflicting with its legal validity are shown for the most important groups of medicines. The authors, members of the presidium of the Hungarian Pharmacopoeia Commission, outline the future face and the timing of the publication of the 8th edition of the Hungarian Pharmacopoeia, which is intended to consist of the translations of the general chapters and monographs of the 3rd and 4th Editions of European Pharmacopoeia as well as of the so called national volume with monographs not included in the EP but harmonized with its general chapters. The impact of the new pharmacopoeia on the different fields of pharmacy and the necessary measures to be taken to make the switch-over from Ph. Hg. VII to Ph. Hg. VIII as smooth as possible are also summarised in the paper. PMID- 11769104 TI - Are single indicators of deprivation as useful as composite indicators in predicting morbidity and mortality: results from the Central Clydeside Conurbation. AB - Analysis of 1991 Census data for the Central Clydeside Conurbation suggests that male unemployment and car ownership provide useful alternatives to composite deprivation indices in predicting health. PMID- 11769105 TI - Evaluation of the volunteer stroke service in Scotland. PMID- 11769106 TI - Developments and challenges for postgraduate dental education in Scotland. PMID- 11769107 TI - Whooping cough in Scotland--the next epidemic. PMID- 11769108 TI - Health issues in remote and rural areas. AB - In March 1996 a conference on the theme health issues in remote and rural areas was held in Inverness. Sponsored by the Scottish Office, Highland Health Board and the Department of General Practice and Primary Care, University of Aberdeen, participants included representatives from the Scottish Office, the seven Health Boards with areas designated as remote and rural, the Health Education Board for Scotland, The Royal College of General Practitioners, voluntary sector organisations and academics. In this paper we introduce the theme and outline the debates detailed in the following three papers. PMID- 11769109 TI - Health and poverty in rural Scotland. AB - This paper presents findings from a study on rural disadvantage to explore the implications of disadvantage for the health of rural communities and the organisation and delivery of health care services in rural areas. Rural health research has been a neglected topic. Yet previous research has reported the importance local people and practitioners place on the provision and organisation of health services in rural areas.' The research reported in this paper further emphasises this point and, in addition, provides empirical data on local people and practitioners perceptions of health issues and health services in four areas of rural Scotland. PMID- 11769110 TI - Rural general practice: a personal view of current key issues. AB - We know much less about health care needs and provision in rural areas than we do about urban areas, particularly the inner cities. Although rural areas are attractive, isolation and lack of accessible services create problems for residents, particularly for those without transport. Analysis of the problems is handicapped by the lack of generally acceptable definitions of the meaning of rurality and remoteness. Rural deprivation is not reflected in commonly used indices of deprivation and is often "hidden". There is a shortage of general practitioners and concern that the situation is deteriorating. What does this mean for the future? Should there be a 'rural track' in educational programmes for rural health workers? How can we harness telemedicine to improve communication between rural dwellers and primary health care, and between primary and secondary health care? Where will nurse practitioners fit into the picture? If centralised services (e.g. for accident and emergency) lead to higher quality of care, how can rural dwellers have equitable access? Some possible solutions are presented. PMID- 11769111 TI - The effect of access factors on breast screening attendance on two Scottish islands. AB - The National Health Service Breast Cancer Screening Programme began in the Argyll and Clyde Health Board area in 1990. The Health Board area is large and includes 26 inhabited islands, thus necessitating the use of mobile screening units. This study examined factors affecting attendance for mammorgraphy on two islands in the west of Scotland, Islay and Jura, using these mobile screening units. The methods used were a prospective postal questionnaire survey prior to breast screening and personal interviews with attenders after screening. All 313 women who were invited to attend for breast cancer screening on Islay and Jura were sent the pre-screening questionnaire. Five were returned by the Post Office with incorrect addresses. Of the remaining 308 women, 234 (76%) returned the questionnaire, with a differential response rate of 84% for participants and 55% for non-participants. One hundred and sixty-three women were interviewed after attending for screening. Non-participants lived further from the screening site than participants (p < 0.01). Non-participants also tended to be in the oldest age group (60-64 years old) (p < 0.05). According to the post-screening interviews, 14% of participants travelled more than 30 minutes to the screening site. Attendance was lowest in the afternoon, when public transport was difficult to obtain. These results suggest that access has an important effect on screening uptake in remote and rural areas. Further consideration should be given to using more than one site in rural areas with long distances and limited public transport. PMID- 11769112 TI - Dosage of antidepressant medication dispensed in Scotland. AB - OBJECTIVES: To examine the daily doses of the more frequently prescribed antidepressants in Scotland and to assess the extent of adequate dosage and its relationship to drug type. DESIGN: Monthly random sample of all prescriptions dispensed in Scotland over 1 year. Antidepressants were categorised into 5 groups, older tricyclics, newer tricyclics, atypical antidepressants, selective serotonin uptake inhibitors (SSRI's) and monoamine oxidase inhibitors (MAOI's). Percentage of prescriptions at or above the minimum effective dose was calculated for each group. In addition the total number and rank order of all antidepressant prescriptions in 1995 were calculated in order to examine sampling bias. SETTING: Prescription data routinely collected by the Pharmacy Practices Division of the Common Services Agency of The NHS in Scotland. RESULTS: Older tricyclics continue to be the most frequently prescribed antidepressants (51%), followed by SSRI's (34%), newer tricyclics and atypicals (7% each) and MAOIs (1%). Only 18% (95% C.I. 13-23%) of the sample of older tricyclics were prescribed at or above the minimum therapeutic level, compared to 99% (95% C.I. 95-100%) for SSRIS' 76% (95% C.I. 55-93%) for atypicals and 74% (95% C.I. 52-96%) for lofepramine. CONCLUSIONS: Despite initiatives to improve the treatment of depressive illness in primary care, the majority of prescriptions continue to be for older tricyclic antidepressants at sub-therapeutic dosage. Incorporation of consensus statement guidelines about minimum effective doses for these drugs in the BNF may be an important and economical route to improving treatment of identified depressive illness. PMID- 11769113 TI - Lothian inter-agency child protection guidelines: impact on a children's NHS trust. AB - OBJECTIVE: To evaluate the process involved in cases of suspected child abuse within a children's NHS Trust, 6 months after implementation of new inter-agency Child Protection guidelines. DESIGN: Prospective evaluation of case records. SETTING: Four departments within a combined child health trust in Edinburgh. MAIN MEASURES: Review of practice within each department, according to the Inter Agency guidelines. RESULTS: No standard procedure existed for the child protection process prior to the guidelines. In the first 6 months following implementation of the guidelines, a substantial increase in workload was experienced by community paediatricians. Medical examinations were better co ordinated, with fewer children receiving repeated, intrusive examinations. However, note keeping was deficient, as 3% of referrals did not appear to be recorded in the case notes. Cross-referencing between departments was variable, with 81% of cases referred to Community Child Health not recorded in hospital case notes. CONCLUSIONS: The Inter-Agency guidelines have resulted in better coordination of the early referral stages. Deficiencies highlighted in this audit are due to record keeping and lack of liaison between departments within a combined children's trust. PMID- 11769114 TI - Changing roles of nurses in Scotland. A survey of developing clinical roles within NHS trusts in Scotland. AB - OBJECTIVES: A position paper to enhance understanding of:- the range of role developments within nursing in Scotland; the educational and managerial preparation planned and undertaken for the introduction of new nursing roles; the implications of new roles with regard to working practices, career development and organisational issues; the perceived benefits and drawbacks of new roles; the nature of role evaluations; plans for future development. DESIGN: A survey of eighteen executive Nurse Directors across Scotland who were interviewed about new clinical roles for registered nursing staff currently being developed within their NHS Trust. A postal survey was also conducted including the remaining NHS Trusts in Scotland. A sampling framework was constructed based on: geographical location (at least one NHS Trust from each of the twelve Mainland Health Board areas was sampled); type of NHS Trust (sample was undertaken to include a representation of major teachinghospitals, district general hospitals and community and mental health services). SETTING: NHS Trusts in Scotland. August October 1995. SUBJECTS: Executive Nurse Directors and in some settings Nurse Managers and nurses undertaking new roles in NHS Trusts in Scotland. RESULTS: New roles identified for nurses fitted into two main categories:- additional skills which were new to existing roles; developing posts which incorporated many new skills. There were four types of developing posts:- Medical Support Nurses; Clinical Nurse Specialists; Advanced Practitioners; Practice Development Facilitators. CONCLUSIONS: New roles for nurses were considered to be beneficial for patients, nurses and the organisation. Protocol usage and educational input into the new roles was variable. Formal evaluation was not well established at the time of the survey. PMID- 11769115 TI - The chief scientist reports ... co-ordination of care on discharge from hospital into the community for patients with HIV/AIDS in Lothian. AB - OBJECTIVE: To document service use by people living with HIV/AIDS discharged from hospital, to identify gaps and overlaps in service provision after discharge, and to evaluate liaison between hospital-based and community-based services. DESIGN: Four week follow-up diary and interview study of service users, and interview/questionnaire study of service providers. SETTING: Services used by people discharged from the wards of two units of two Lothian hospitals. SUBJECTS: All patients with HIV infection admitted to the wards of two units of two Lothian hospitals from October 1992 to February 1993, and their service providers. RESULTS AND CONCLUSION: General practitioners were the most contacted service post discharge, but general practitioners did not appear to play a co-ordination role in service provision. Liaison on discharge was found to be effective in terms of continuity of care in most cases; and from a service user perspective, liaison between hospital and primary care agencies did not appear a major concern. The majority of hospital discharges were organised in a setting with a large number of services, with complex communication patterns and informal procedures of discharge arrangements. This created uncertainty among service providers as to the arrangements which had been made, and fear and anxiety that they fall through. On the other hand, the informality of discharge procedures also ensured flexibility and responsiveness to unexpected events and changes in service users' circumstances and was a vital factor in continuity of care experienced by them. A more important issue for service users was the poor integration of services concerned with social/material support in the system of medical and emotional care. PMID- 11769116 TI - The evaluation and management of dyslipidemia in HIV-infected patients. PMID- 11769117 TI - Top 200 medicines: can new actions be discovered through computer-aided prediction? AB - Computer-aided prediction of the biological activity spectra by the program PASS was applied to a set of 130 pharmaceuticals from the list of the Top 200 medicines. The known pharmacological effects were found in the predicted activity spectra in 93.2% of cases. Additionally, the probability of some supplementary effects was also predicted to be significant, including angiogenesis inhibition, bone formation stimulation, possible use in cognition disorders treatment, multiple sclerosis treatment, etc. These predictions, if confirmed experimentally, may become a cause for a new application of pharmaceuticals from the Top 200 list. Most of known side and toxic effects were also predicted by PASS. PASS predictions at earlier R & D stages may thus provide a basis for finding new "leads" among already launched drugs and may help direct more attention to those particular effects of pharmaceuticals in clinical use which become apparent only in a small part of the population and require additional precautions. PMID- 11769118 TI - An approach for visualization of the active site of enzymes with unknown three dimensional structures. AB - A new approach for virtual characterization of the active site structure of enzymes with unknown three-dimensional (3D) structure has been proposed. It includes analysis of data on enzyme interaction with reversible competitive inhibitors, their 3D structures and moulding of the substrate-binding region. The superposition of ligands in biologically active conformations allows to determine the shape and dimension of the active site cavity accommodating these compounds. Monoamine oxidase A (MAO-A), a "typical" enzyme with unknown spatial organisation, was used to test this method. The correctness of such approach was validated by the analysis of HIV protease interaction with its inhibitors using 3D structures of their complexes. Mould of the substrate/inhibitor binding site can be used for the visualization of this binding site and for searching new ligands in molecular databases. PMID- 11769119 TI - Cytochrome P450 database. AB - This paper describes a specialized database dedicated exclusively to the cytochrome P450 superfamily. The system provides the impression of superfamily's nomenclature and describes structure and function of different P450 enzymes. Information on P450-catalyzed reactions, substrate preferences, peculiarities of induction and inhibition is available through the database management system. Also the source genes and appropriate translated proteins can be retrieved together with corresponding literature references. Developed programming solution provides the flexible interface for browsing, searching, grouping and reporting the information. Local version of database manager and required data files are distributed on a compact disk. Besides, there is a network version of the software available on Internet. The network version implies the original mechanism, which is useful for the permanent online extension of the data scope. PMID- 11769120 TI - Molecular lipophilicity calculations of chemically heterogeneous chemicals and drugs on the basis of structural similarity and physicochemical parameters. AB - QSARs based on molecular polarizability (alpha) and H-bond acceptor factors (sigma Ca) as independent variables provided good predictability of octanol/water partition coefficients (P) for chemicals and drugs. However, for some molecules containing few functional groups, the calculated values deviated significantly from those observed. This approach gave good results when applied to a set of 138 chemicals and drugs previously studied by Mannhold and Dross who compared other methods to calculate log P values. At the same time, three variations on a molecular similarity approach were pursued. In this study, a large training set with experimentally determined octanol/water partition coefficients (P) was searched for structures closely related to the compound-of-interest. The most successful of these variations took the mean log P value of few most closely related compounds after each was adjusted for differences between their and the compound-of-interest's polarizabilities (alpha) and H-bond acceptor capacities (sigma Ca). PMID- 11769121 TI - Molecular modelling of disease-causing single-nucleotide polymorphisms in collagen. AB - The purpose of the work was to investigate at the molecular structural and energy levels the consequence of amino acid substitutions in collagen that cause systemic diseases. The data have been systematized on defects in human collagen III, and the patterns of single-nucleotide polymorphisms collected. Then molecular mechanics calculations were performed for native and mutant collagen molecule fragments. The observed energy components and structural alterations that accompany particular amino acid substitutions were used to propose an interpretation of negative consequences in terms of stability and hydration of the macromolecule. PMID- 11769122 TI - The learned symmetry concept in revealing quantitative structure-activity relationships with artificial neural networks. AB - A method to build QSAR models based on substituent constants for congeneric sets of compounds having several topologically equivalent substituent positions was proposed. The approach is based on the application of artificial neural networks (learning to construct nonlinear structure-activity relationships taking into account necessary symmetry properties of training set structures) to a training set expanded by adding the copies of compounds with the same activity values but with permuted assignment of equivalent substituent positions. The better predictive power of these constructed models, as compared with the performances of neural network models for non-expanded sets was demonstrated for the calcium channel blockers of 1,4-dihydropyridine type and for hallucinogenic phenylalkylamines. PMID- 11769123 TI - [Cell determination and differentiation: a concept of gene clusters]. AB - This paper formulates a conception of cluster organization of the genetic material, responsible for cell determination and differentiation in multicellular organisms. According to this conception, gene controlling each particular stage of these processes are functionally integrated via genes-activators into gene groups (clusters) of different levels of hierarchy. Besides, some hypotheses of molecular mechanisms providing the action of these gene groups have been put forward. Attempts were made to elucidate some phenomena of cell differentiation, specifically a drop or a complete loss of dividing ability in highly specialized cells, in addition to a property of the cell to remember the history of its own development inside the organism, and to inherit the ancestor's direction of differentiation. Attention was paid to a mechanism (originating from this conception) of the emergency of malignant tumors, which means that cells giving rise to tumors are known to evade primarily their involvement in the process of further specialization. Besides, mechanisms of a molecular supply of positional information are examined. Phylogenetic aspects concerning the standing of the fragment of genetic apparatus controlling cell specialization, and the development of its inner hierarchy that involves subordination of some clusters to other ones. PMID- 11769124 TI - [Oogenesis of Tilapia mossambica. III. The cytoplasm of previtellogenic oocytes]. AB - Using methods of light and electron microscopy and of autoradiography, the morphology of cytoplasm in previtellogenic oocytes of tilapia mossambique was studied. Similar to other bony fishes, mitochondria at the early previtellogenic oocytes are mostly located in the perinuclear cytoplasm to be later distributed over the whole volume of growing oocytes. The Golgi complex is poorly developed. In the peripheral regions of the late previtellogenic oocytes, stickform mitochondria, pinocytotic vesicles and microvilli are observed, along with the perioocyte space formation. In the cytoplasm of previtellogenic oocytes polyribosomes appear. No differences in 3H-leucine incorporation intensity was noticed in oocytes of different previtellogenic stages. The characteristic feature of tilapia mossambique previtellogenic oocytes, in comparison with other bony fishes, is the presence of fat droplets in their cytoplasm. PMID- 11769125 TI - [Cytogenetic study of certain Tilia species]. AB - The number of chromosomes, and mitosis and microsporogenesis were studied in Tilia europaea, T. tomentosa, T. cordata and T. platyphyllos under natural conditions of Voronezh region. Significant mixoploidy of meristematic tissue cells in seedling root tips, mitotic activity and meiosis have been demonstrated for the first time. The number of chromosomes in somatic cells varied from 28 to 140-146. The number 2n = 82 was modal for all the studied species. The number of chromosomes in T. europaea has been determined for the first time. The numbers of chromosomes in the genus Tilia are analysed on the basis of the literature and our own data. The peak of mitotic activity in seedlings and juvenile leaves (8 10%) fell on the night: 0-1 a.m. according to the winter time. Microsporogenesis is simultaneous and asynchronous. In some individual trees various abnormalities of meiosis were found: lagging in time in 1 to 5-6 chromosomes, bridges, fusions of spindles. Variations in pollen dimensions, shape and pore number were detected in many trees. PMID- 11769126 TI - [The number of nucleoli in peripheral blood lymphocytes of the Chernobyl accident liquidators]. AB - The number of nucleoli in lymphocyte nuclei was compared in the peripheral blood of the Chernobyl liquidators and non-irradiated persons (control). The former was significantly distinguished from the latter (p < 0.01) by the parameter "the number of nucleoli in lymphocytes", mean numbers of nucleoli per nucleus in these being 1.18 and 1.12, respectively. The increased number of nucleoli in lymphocytes of the Chernobyl liquidators may be associated with cytogenetic radiation effects. PMID- 11769127 TI - [Immortalization of human fibroblasts using tsA mutant of SV40 and pSV3neo plasmid]. AB - Clones of immortalized human fibroblasts with an extended life span in culture and a capability of subloning were obtained after the infection with a temperature sensitive mutant (tsA 239) of SV40 virus and pSV3neo plasmid. As compared with the parental cells, the obtained clones exhibited increased plating efficiency, decreased doubling time, and serum dependence. We did not obtained the colony formation during cultivation of immortalized cells in semiliquid agar. This means that our cells were not completely malignant. The PCR (polymerase chain reaction)-analysis has revealed the presence of viral DNA at early passages (25th passage) after the infection by tsA SV40, and its absence after a prolonged cultivation (46th passage). PCR-analysis of the clones obtained after pSV3neo transfection has revealed the presence of gene A sequences either at early (9 15), or later (62) passages. The expression of the gene A product in cells of these clones was revealed only early passages (11 and 35). Possible mechanisms of immortal phenotype origin in human diploid cells after the action of ts-mutant and other constructions of SV40 are discussed. PMID- 11769128 TI - [Olfactory stress and modification of phagocytosis in peripheral blood cells of adult male mice]. AB - Data on pheromonal influence on phagocytic activity of leukocytes in peripheral blood of adult randombred and CBA male mice have been obtained. The identified mouse pheromone 2,5-dimethylpyrazine was used, which induces some physiological effects associated with reproduction in both mouse males and females. Significant differences in spontaneous level of phagocytosis were between inbred CBA and randombred animals: the frequency of phagocytic cells was lower in CBA males by 1.4 times. The substance tested here induces phagocytosis in randombred (by 1.7 times) males. A low dose of 2,5-dimethylpyrazine (similar to the natural pheromone concentration) induces a higher increase in phagocytic activity by leukocytes. Possible mechanisms of pheromonal action on phagocytosis are discussed with the perspectives of finding highly effective immunomodulators among mammalian pheromones. PMID- 11769129 TI - [Constitutive activity of MAP kinase cascades in REF cells transformed by E1A and cHa-ras oncogenes]. AB - Proteins of Ras family play an important role in regulation of cell growth and proliferation, and their mutations can lead to growth factor-independent proliferation due to constitutive activity of various signal transduction cascades. In the present work, we studied the activity of ERK, JNK and p38 MAP kinase cascades in rat embryo fibroblast cells transformed with oncogenes E1A and cHa-ras. These transformed cells are characterized by a high and non-regulated activity of transcription factor AP-1 involved in the regulation of cell proliferation. Since phosphorylation of AP-1 depends on the activity of relevant MAP-kinase cascades (ERK, JNK and p38), we analysed the expression of non phosphorylated forms of the kinases and their phosphorylated state in E1A + cHa ras cells using antibodies specific to non-phosphorylated and phosphorylated proteins. It has been established that transformed cells contain higher amounts of non-phosphorylated ERK, JNK and p38 kinases, thus implying a reduced degradation of these and other proteins in the transformants. The content of phosphorylated (active) forms studied in Western blot-analysis with phosphoantibodies was shown to be also higher in exponentially growing E1A + cHa ras cells. But serum stimulation of the starved cells gave insignificant rise to an increase of ERK, JNK and p38 phosphorylation. Nevertheless, an in vitro kinase assay performed with the kinases, either immunoprecipitated by antibody or bound to GST-fusion substrates, enabled us to show a certain level of stimulation of c Jun-associated (JNK) and MEF2A-associated (p38) kinase activity in serum stimulated E1A + cHa-ras cells. Thus, the obtained results show that transformation of fibroblasts with E1A and ras oncogenes may contribute to constitutive activation of ERK, JNK and p38 kinase cascades responsible for a high and non-regulated activity of MAP-kinase-dependent transcription factors, in particular AP-1. PMID- 11769130 TI - [Effect of lithium ions on the growth of wheat roots and the role of phosphoinositide cycle in growth regulation]. AB - The influence of lithium ions (LiCl in concentrations of 0.5, 1.0, and 5.0 mM) on the growth processes of roots of 2-5-day old wheat seedlings was studied. It was shown that the inhibition of the root growth increased with the increase of LiCl concentration and seedling age. The membrane potential of root cells was lower and the loss of K+ by cells was greater when roots were treated with 5 mM LiCl, compared with the control. The growth inhibition by lithium was decreased by univalent ions, partially by potassium at the beginning of growth and completely by sodium throughout the experimental period. The divalent ions calcium and barium decreased the Li(+)-induced inhibition of root growth by reducing the rate of lithium uptake by cells. Myoinositol, controlled by Li-sensitive inositolmonophosphatase, reversed the Li-induced root growth inhibition in 2-day old seedlings, but did not prevent the inhibition during subsequent elongation. It can be concluded that lithium effects on wheat root growth are mediated by a partial blockage of signal transduction for proliferation (via the phosphoinositide cycle), because of calcium deficiency and caused by modification of ion transporting systems of the plasmalemma, and by disturbance of ion gradients, primarily H+ and K+. PMID- 11769131 TI - [Potential functional differentiation of genome in the course of evolution and approaches to its study. I. Neontological annals of evolution and its analysis]. AB - It is shown that the division of phylogenetical branches descends anisotomically. One new branch becomes evolutionary not active. Another one continues actively to develop. It allows to consider a system of present-day organisms as neonatological annals of evolution. A question arises on distinctions in the constitution of genomes of organisms belonging to active and inactive phylogenetic branches. PMID- 11769132 TI - [Potential functional differentiation of genome in the course of evolution and approaches to its study. II. Elucidation of diversity of phylogenetic lines]. AB - It has been shown elsewhere (Chupov, 2001) that the branching of phylogenetical trunks goes by anisotomical way. Thus, in one of newly formed branches a possibility remains of a further evolutionary transformation, while taxa belonging to another branch sink into a prolonged evolutionary stasis. In the author's opinion, such a phenomenon is to be accompanied by distinctions in constitution of genetical cell devices of the taxa belonging to the branches with evolutionary contrasting potencies. In the article, an attempt is done to consider some other approaches relevant to this problem. PMID- 11769133 TI - [Triploidy in populations of three species of black flies of the genus Prosimulium roubaud (Diptera, Simuliidae)]. AB - Karyotypes of 94 larvae belonging to species of black flies of the genus Prosimulium Rouband were studied on aceto-orcein stained squashes of 94 larvae belonging to three species of Prosimulium: P. isos Rubzov, P. pecticrassum Rubzov, and P. pamiricum Chubareva et Petrova. All the larvae appeared to be triploid parthenogenetic females, with no males being found. The structural peculiarities of these polytene chromosomes suggest a heterozygous nature of the examined larvae. PMID- 11769134 TI - Are you ready for anthrax, or worse? You must revamp your bioterrorism plan. AB - A study has shown that EDs are unprepared to handle mass casualties of bioterrorism, and plans must be revamped. Alternate care and triage areas must be selected in advance and may include parking lots and hallways between buildings. Care for contaminated patients in areas that can be abandoned, so regular patient care areas are not disrupted. Have a system in place to decontaminate patients before they enter the ED. PMID- 11769135 TI - Use this proven system for disaster communications. AB - The Hospital Emergency Incident Command System (HEICS) system uses a logical management structure, defined responsibilities, and clear reporting channels to help the hospital communicate with outside emergency responders. The system is considered a benchmark for EDs to implement as an integral part of your disaster plan. Flow charts and job action sheets are used to clearly define responsibilities of individuals. The system uses the same terminology as other first responders, so communication is easier. PMID- 11769136 TI - Here are options for communicating. PMID- 11769137 TI - Boost bottom line with research nurse. AB - The salary of a full-time research nurse can be supported with funds from industry-sponsored clinical trials. ED nurses and physicians may be too busy with clinical tasks to undertake research projects. A dedicated research staff member can improve the quality of research. Research nurses also can assist staff with projects and handle patient follow-up. PMID- 11769138 TI - Very high background radiation areas of Ramsar, Iran: preliminary biological studies. AB - People in some areas of Ramsar, a city in northern Iran, receive an annual radiation absorbed dose from background radiation that is up to 260 mSv y(-1), substantially higher than the 20 mSv y(-1) that is permitted for radiation workers. Inhabitants of Ramsar have lived for many generations in these high background areas. Cytogenetic studies show no significant differences between people in the high background compared to people in normal background areas. An in vitro challenge dose of 1.5 Gy of gamma rays was administered to the lymphocytes, which showed significantly reduced frequency for chromosome aberrations of people living in high background compared to those in normal background areas in and near Ramsar. Specifically, inhabitants of high background radiation areas had about 56% the average number of induced chromosomal abnormalities of normal background radiation area inhabitants following this exposure. This suggests that adaptive response might be induced by chronic exposure to natural background radiation as opposed to acute exposure to higher (tens of mGy) levels of radiation in the laboratory. There were no differences in laboratory tests of the immune systems, and no noted differences in hematological alterations between these two groups of people. PMID- 11769139 TI - Factors increasing the mortality rate for patients with ruptured abdominal aortic aneurysms. AB - The objective of this report was to analyze the current surgical results of operative treatment in patients suffering ruptured AAA (abdominal aortic aneurysms) and to define those independent predictive factors for mortality. During a period of 2 years, from January 1996 to December 1997, 144 patients operated on for ruptured AAA in 10 hospitals were included in a multicenter retrospective study. Among the collected variables concerning each patient, those with potential relation to surgical mortality were studied: gender, age, diabetes, hypertension, cardiopathy, pulmonary obstructive disease, preoperative renal dysfunction, symptomatic cerebrovascular disease, peripheral vascular disease, hematocrit on admission, preoperative hypotension < 80 mmHg, loss of consciousness, cardiac arrest, aortic aneurysm location (infrarenal versus non infrarenal), iliac involvement, aneurysm size, type of rupture, left renal vein ligature, ligature of a patent inferior mesenteric artery, place of aortic cross clamping, type of grafting, exclusion of both hypogastric arteries, venous technical complications, associated surgery, use of cell saver, intraoperative blood loss, and postoperative complications (renal failure, sepsis, coagulopathy, cardiac complications, pulmonary complications, colon ischemia, prosthetic graft complications, and need for reoperation). Those variables with statistical significance in the univariate analysis were introduced into a multivariate logistic regression model to determine the independent predictors of death. From our results we concluded that surgery for ruptured abdominal aortic aneurysms continues to have an excessively high mortality rate. Even though some preoperative variables could be identified as predictors of mortality, an absolute mortality risk has not yet been determined and the decision to negate surgery should be individualized rather than taken on that basis only. Early diagnosis and treatment of symptomatic aneurysms would improve mortality figures and selective screening should be contemplated. PMID- 11769140 TI - Early vascular complications after endovascular repair of aortoiliac aneurysms. AB - The purpose of this study was to estimate the frequency of and review the treatment options for intraoperative endograft access-related vascular complications and early postoperative vascular complications of endovascular repair for aortoiliac aneuryms (EVAR). Between February 1998 and April 2000, 53 patients (46 males, 7 females) with aneurysms of the abdominal aorta (AAA) and iliac arteries were treated with endovascular grafts (48 AAA, and 5 iliac aneurysms). All procedures were performed using open exposure of the femoral arteries. One patient with an AAA was converted to open repair (primary technical success, 98.1%). We recorded the need for adjunctive vascular procedures or intervention to the access arteries (iliofemoral) or the endograft because of thrombosis or distal embolization. Events were classified as either intraoperative, early postoperative (< 30 postoperative days), or late postoperative. Their etiology and treatment were recorded. The results were compared to those from other series reported in the literature and to published registry data. From our results we concluded that the need for adjunctive vascular procedures to the iliofemoral arteries at the time of EVAR is significant. These procedures are necessary to either repair damage to the access arteries from the delivery system or provide a conduit for graft delivery in cases where the access arteries are inadequate. Early postoperative vascular complications are due to technical factors resulting in residual graft limb stenoses. Both intraoperative and early postoperative vascular complications after EVAR are more common in female patients. These complications can be effectively treated with a variety of open surgical and transfemoral endovascular techniques. PMID- 11769141 TI - Incidence of major venous and renal anomalies relevant to aortoiliac surgery as demonstrated by computed tomography. AB - Preoperative knowledge of the presence of major venous anomalies facilitates the safe performance of aortic surgery. The purpose of the study was to estimate the incidence, as detected by abdominal and pelvic computed tomography (CT), of major venous and renal anomalies related to the abdominal aorta in an adult population. A total of 1822 intravenous contrast-enhanced abdominal and pelvic CT scans done in 1822 patients at two university teaching hospitals were randomly selected and prospectively reviewed (between June 1999 and March 2000) to identify major venous and renal anomalies associated with the abdominal aorta and iliac arteries. An interpreting staff radiologist then indicated on adata sheet whether any of the following anomalies were present or absent: (1) retroaortic left renal vein, (2) circumaortic left renal vein, (3) left-sided inferior vena cava (IVC) without situs inversus, (4) left-sided IVC with situs inversus, (5) duplicate IVC, (6) preaortic confluence of the iliac veins, or (7) horseshoe kidney. The CT scans reviewed had been performed for a wide variety of indications. Thirty-four scans were excluded from the study because either the anomalies we were looking for could not be assessed for technical reasons or the patient had a previous left nephrectomy and therefore assessment of the left renal vein was impossible. From this analysis we found that in an adult population, the prevalence of major venous and renal anomalies related to the abdominal aortaand iliac arteries and detected by CT scan was 5.65%. Prior to aortic surgery, preoperative knowledge of the presence of such anomalies helps with operative planning and may reduce the risk of major venous hemorrhage associated with these anomalies. PMID- 11769142 TI - Effect of the thawing process on cryopreserved arteries. AB - This study was designed to explore the changes that occur in cryopreserved pig arteries following different thawing procedures, before and after being placed in an in vitro flow circuit. Segments of minipig iliac artery were cryopreserved in complete minimal essential medium plus 10% dimethylsulphoxide and stored in liquid nitrogen at -196 degrees C for 30 days. Three study groups were established according to whether the arterial specimens were fresh (control, n = 20), cryopreserved and rapidly thawed (RT) at 37 degrees C (n = 22) or cryopreserved and subjected to controlled, automated slow thawing (ST) (n = 22). Half of the specimens of each group were subsequently placed in the flow circuit for 72 hr. Evaluation was made of morphological and ultrastructural changes. Cell damage was established using the TUNEL method. All cryopreserved specimens showed endothelial denudation that was most extensive in those subjected to rapid thawing. Slowly thawed specimens showed improved cell viability and organization of the vessel wall, compared to those thawed rapidly. Under conditions of flow, the damage induced by the freezing/thawing process was enhanced. These findings suggest that (a) slow thawing of cryopreserved arteries results in improved preservation of the structure and viability of vessels, and (b) the damage induced by freezing/thawing is enhanced when vessels are subjected to flow in an in vitro circuit. PMID- 11769144 TI - Tibial bypass using complex autologous conduit: patency and limb salvage. AB - Over an 8-year period, we performed 93 lower extremity bypasses using complex autologous conduits, which included (1) contralateral greater saphenous vein (GSV), (2) composite GSV, (3) superficial femoral vein, (4) lesser saphenous vein, (5) cephalic or basilic veins, and (6) composite-sequential (PTFE and vein) grafts. These grafts represented 16% of all infrainguinal bypasses during this period, and all grafts were performed to treat limb-threatening ischemia. Survival, patency, and limb salvage were examined by the life-table method. Primary graft patency was 46 and 38% at 3 and 5 years. Assisted-primary patency was 62 and 59%, and secondary graft patency rates were 68 and 64% at 3 and 5 years. Twenty-nine bypasses (31%) required revision to restore or maintain patency. The 3-year limb salvage rate was significantly better when revision was performed for graft stenosis than for graft thrombosis (90% vs. 46%, p < 0.05). Overall limb salvage rate was 73% at 5 years. The mortality rate was 5.4% and the 5-year survival was 51%. Complex autologous tibial bypasses provided acceptable long-term limb salvage in patients with severe ischemia and inadequate ipsilateral GSV. The increased operating time and complexity required did not produce prohibitive operative risks. Postoperative graft surveillance in these complex vein bypasses allowed revision in many cases before graft occlusion occurred and significantly improved long-term limb salvage. PMID- 11769143 TI - Relationship of the 20S proteasome and the proteasome activator PA28 to atherosclerosis and intimal hyperplasia in the human vascular system. AB - Down-regulation of the proteasome activator PA28 results in abnormal proteasome activation and has been implicated in the development of intimal hyperplasia (IH) in animal models. Demonstration of proteasome and PA28 expression has not yet been documented in the human vascular system. This study sought to define the distribution of the 20S proteasome and its activator PA28 in human vessels and determine the relationship between the expression of the proteasome and PA28 and the development of atherosclerosis and IH. Vascular biopsies were obtained from 70 patients at the time of surgery, were snap frozen and sectioned in 5-micron sections, and prepared using standard histological techniques. The immunoperoxidase technique was used to identify 20S proteasome and PA28 expression in diseased and normal human arteries and veins as well as in patent bypass grafts with and without IH. Expression was graded by a blinded pathologist (scale: 1-4). Repeat quantification of the immunopositive cells was also performed. Expression of 20S proteasome and PA28 was identified in all vascular tissues examined. The proteins were identified predominately within the cytoplasm of vascular smooth muscle cells and endothelial cells. PA28 was more intensely expressed in quiescent regions of the vessel wall as compared to areas undergoing active proliferation and remodeling. PA28-mediated activation of the proteasome may be necessary to maintain normal cellular homeostasis and prevent excessive cellular proliferation in the human vascular system. Abnormalities of proteasome activation may have a significant role in the development of atherosclerosis and IH. PMID- 11769145 TI - Indications for directed thrombolysis or new bypass in treatment of occlusion of lower extremity arterial bypass reconstruction. AB - The long-term results after directed thrombolytic therapy for thrombosis of infrainguinal arterial bypass reconstructions are disappointing if broad indications are applied. This work presents criteria for determining the indications for thrombolysis or the insertion of a new bypass. In a retrospective study we compared the secondary cumulative patency after bypass thrombolysis (n = 82) and after replacement bypass (n = 143). Using multivariate analysis, the influence of prognostic factors on secondary long-term patency was investigated. Our results showed that brief occlusions (< or = 3 days) in older bypasses (> or = 11 months) should be treated by thrombolysis. In all other cases, efforts should be made to replace the bypass with autologous vein. In the absence of autologous vein, we found umbilical vein to be a suitable material for vessel replacement. PMID- 11769146 TI - Impact of endovascular-assisted in situ saphenous vein bypass technique on hospital costs. AB - Our initial experience with endovascular-assisted in situ saphenous vein bypass (EISVB) showed patency rates to be comparable to those with conventional in situ bypass, and resulted in a significant reduction in wound-related complications and hospital length of stay (LOS). Here we evaluate the relative costs of these two approaches. Forty-four patients underwent 46 EISVB procedures using endovascular cannulation and coil occlusion of the saphenous vein side branches. Costs for each patient for the operation, the associated hospital stay, and any postoperative care were assessed. These costs were compared to those of the last 46 conventional open in situ bypass procedures as an historical comparison group. The two groups were statistically similar for all parameters except distal outflow target, with the comparison group having statistically more pedal bypasses (p = 0.004). Subset analysis was performed by subdividing each operative group, into those with popliteal and those with distal bypasses. The results of our analysis led us to conclude that the shorter LOS following EISVB more than compensates for the initial cost incurred by the side branch occlusion system. This shorter stay translates into an overall cost savings for EISVB compared to the cost of conventional in situ bypass. The reductions in wound-related morbidity and recovery time postoperatively with EISVB add an additional long term cost benefit. PMID- 11769147 TI - Comparison of clinical outcome of stripping and CHIVA for treatment of varicose veins in the lower extremities. AB - The purpose of this nonrandomized case-review study was to compare the outcome of stripping and CHIVA for treatment of varicose veins in the lower extremities in our department. Outcome was evaluated by independent physicians. A total of 85 patients underwent saphenous vein stripping in association with phlebectomy and 90 patients underwent CHIVA cure. The duration of follow-up was 3 years. Study criteria were (1) presence of varicose veins as a cause of failure (1.1% in the CHIVA group vs. 15.3% in the stripping group), (2) appearance of telangiectasia (8.9% in the CHIVA group vs. 65.9% in the stripping group), (3) patient dissatisfaction rate (3.3% in the CHIVA group vs. 16.5% in the stripping group), (4) postoperative symptoms as a cause of failure (1.1% in the CHIVA group vs. 21.2% in the stripping group), and (5) saphenous nerve injury (1 patient in the CHIVA group vs. 16 in the stripping group). Differences between all five criteria were significantly in favor of the CHIVA group as compared to saphenous vein stripping with phlebectomy. Clinical results at 3 years are better for patients treated with CHIVA than stripping with regard to presence of varicose veins, clinical symptoms, presence of telangiectasia, cosmetic satisfaction, and neurologic complications. Data in our series of CHIVA treatments are comparable to those reported in the literature and better than those described in three series of stripping procedures with 3-year follow-up. A prospective randomized study is now underway to confirm these findings. PMID- 11769148 TI - Comparison of intraoperative and postoperative duplex ultrasound for carotid endarterectomy. AB - Intraoperative (IO) duplex ultrasound (DU) is used to identify correctable technical defects at the time of carotid endarterectomy (CEA). Postoperative (p.o.) DU is used to evaluate recurrent or residual stenosis. We compared IO and p.o. DU to determine the value and significance of these studies in the management of patients undergoing CEA. We performed completion IO DU following CEA and p.o. DU a mean of 8 weeks after surgery in 78 patients. IO studies were performed by the operating surgeon and p.o. studies were performed in an accredited vascular laboratory. Peak systolic velocity (PSV) was measured in the internal carotid (ICA), external carotid, and common carotid (CCA) arteries. The criteria used for an abnormal study were an ICA PSV > 150 cm/sec and a ratio of ICA to CCA PSVs(ICA/CCA) > 3.0. Completion angiograms were also performed on all patients intraoperatively. Technical defects identified on DU or angiogram were corrected whenever possible. From our results, we concluded that in many patients, early p.o. DU will demonstrate an elevated ICA PSV compared to the IO PSV. If the ICA/CCA remains normal, this increase is unlikely to represent a clinically relevant recurrent or residual stenosis. A postoperative ICA/CCA ratio > 3.0 may be a more reliable indicator of significant stenosis and a lesion that is likely to progress or occlude than PSVs alone. PMID- 11769149 TI - Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile? AB - It has been reported that carotid screening may be cost-effective in patient populations in which the prevalence of severe carotid stenosis exceeds 4.5%. In order to identify potential patient populations who might benefit from carotid screening, we examined the results of preoperative duplex scanning in patients undergoing open heart surgery. Between January 1995 and July 1998, 3708 patients (59% male, 41% female) underwent open heart surgery at our institution. Of these, 3081 underwent coronary artery bypass grafting (CABG), 364 underwent valve replacement (VR), and 263 underwent CABG and VR. The ages of these patients ranged from 40 years to 98 years (mean 68 +/- 11 years). The risk factors analyzed included hypertension (HTN), 59%; smoking (Smk), 53%; and diabetes (DM), 33%. Patients were divided into three groups according to their age. Group A consisted of the 835 patients who were < or = 60 years old, group B consisted of 2474 patients ranging from 61 years to 80 years old, and group C consisted of 399 patients who were > or = 81 years old. All patients underwent bilateral preoperative carotid duplex scans at an Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL)-accredited vascular laboratory. Statistical analyses were performed using chi-squared, Fisher's exact test, linear regression, and multivariate analysis. From our results we concluded that carotid screening is not recommended for patients under 60 years of age who are undergoing CABG unless they present with a minimum of two of the following major risk factors: hypertension, diabetes, or smoking. However, carotid screening is recommended for all patients undergoing open heart operations who are over the age of 60 years old, regardless of the absence of associated risk factors. PMID- 11769150 TI - Evaluation of thrombogenicity of fluoropassivated polyester patches following carotid endarterectomy. AB - The use of a patch after carotid endarterectomy (CE) is recommended to reduce the incidence of restenosis. Most studies on this subject report the implantation of saphenous vein or PTFE patches, because polyester has always been considered to be a thrombogenic material. The purpose of this study was to evaluate the thrombogenicity of a knitted polyester patch passivated by fluoropolymer surface treatment (FPD patch), which experimental studies have demonstrated to be less thrombogenic than other materials. This prospective, randomized study was performed in 22 patients who underwent CE. In 11 patients the arteriotomy was sutured directly, while in the other 11 an FPD patch was applied. Patients' 111in oxine labeled platelets were reinjected on the first postoperative day, and scintigraphies were performed after 4, 24, and 48 hr, respectively. The study confirmed that an FPD patch is no more thrombogenic than a simple carotid endarterectomy. The application of the patch, therefore, can be recommended to reduce restenosis without any adjunctive thromboembolic risk. PMID- 11769151 TI - Rupture of mesenteric artery branch aneurysm. AB - We describe a case of ruptured mesenteric artery branch aneurysm. Since it is characterized by nonspecific clinical manifestations, aneurysm in this uncommon location is usually diagnosed following complications. Definitive diagnosis requires Doppler ultrasound followed by arteriography. The purpose of this report is to describe the pitfalls of diagnosis and define an appropriate management strategy. Unlike abdominal aortic aneurysm, isolated aneurysms of the superior mesenteric artery (SMA) branches are rare. Most cases are diagnosed after the occurrence of complications. Early diagnosis would be useful, since the natural course can be tragic without timely treatment. In this report, we describe one case of ruptured mesenteric artery branch aneurysm and review the literature for relevant data on the circumstances of discovery, methods of investigation, and appropriate management of these lesions. PMID- 11769152 TI - Spontaneous dissection of the celiac artery. AB - Spontaneous dissection of the celiac artery (CA) is uncommon, considering the number of isolated lesions without associated aortic dissection and exclusive of abdominal trauma. We have treated five cases of isolated spontaneous dissection of the CA or its branches. There were three men and two women with a mean age of 54 years. The presenting manifestation was acute epigastralgia in three cases and chronic abdominal pain in one. In the remaining case, dissecting CA was a coincidental finding. All patients underwent abdominal Doppler ultrasound and CT scan imaging, which demonstrated aneurysm in three cases and dissection in two. Work-up also included arteriography in three cases and magnetic resonance (MR) angiography in one. Management consisted of emergency surgical repair in three cases and close surveillance in two. The repair procedure was resection anastomosis in one case and prosthetic bypass to the hepatic artery in two cases. Postoperative recovery was uneventful in all three cases and patients were symptom-free at 6, 8, and 18 months. Both patients under surveillance were symptom-free at 1 and 2 years. Because of the risk of ischemic and hemorrhagic complications, surgery should be considered for any patient with CA dissection. However, some patients with uncomplicated asymptomatic lesions may be eligible for medical treatment with regular surveillance. PMID- 11769153 TI - Rupture of internal iliac artery aneurysm into the bladder following aortic aneurysm repair. AB - This report describes a case of ruptured internal iliac artery aneurysm into the bladder after repair of an infrarenal abdominal aortic aneurysm. Aortic repair consisted of resection of the aneurysm followed by prosthetic interposition to reestablish arterial continuity. During the postoperative period, the patient had ischemia of left colon, which was successfully treated by the Hartmann procedure. A right internal iliac artery aneurysm measuring 50 mm in diameter was demonstrated by an abdominal CT scan during the initial hospitalization but was considered stable, since ultrasonography showed no change in diameter at 3 months and 1 year. The patient was lost from follow-up until 3 years later when he was hospitalized after rupture of the right iliac artery aneurysm, then measuring 120 mm in diameter, into the bladder. Surgical repair was undertaken. The procedure involved aortobifemoral bypass with suture of the bladder defect and branches of the internal iliac artery by the endoaneurysmal route. Postoperative recovery was uneventful. Upon reexamination 1 month after discharge from the hospital, the patient was asymptomatic. This rare case confirms the gravity of internal iliac artery aneurysm and the importance of therapeutic management to prevent rupture. PMID- 11769154 TI - Popliteal artery thrombosis secondary to exostosis of the tibia. AB - This report describes an exceptional case of popliteal artery thrombosis secondary to exostosis of the superior extremity of the superior tibia in a young adult. Correct diagnosis was made during re-operation for recurrent thrombosis. Surgical treatment consisted of resection of the bony tumor and venous bypass to reestablish arterial continuity. Femoropopliteal vascular complications of exostosis are rare, with most cases involving arterial aneurysms or false aneurysms. Differential diagnosis in our young patient took into account the other causes of popliteal thrombosis: entrapped popliteal artery, adventitious cyst, fibrodysplasia, and juvenile arteriopathy. In patients with major functional disability, operative treatment is recommended to remove the bony abnormality and repair the arterial lesion. PMID- 11769155 TI - Retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum. AB - This report describes a novel technique used for management of retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum. The procedure consists of endoaortic exclusion of the aneurysmal neck, using a prosthetic patch after sternotomy during circulatory arrest, and antegrade cold blood cerebroplegia. The advantages of this technique are avoidance of hemorrhagic complications during clamping of the aneurysmal neck, limiting of the extent of dissection of the aortic arch, and elimination of the risk of inadvertent left recurrent nerve paralysis. Antegrade cold blood cerebroplegia provides good cerebral protection and decreases the duration and consequences of extracorporeal circulation. PMID- 11769156 TI - Retroaortic left renal vein and its implications in abdominal aortic surgery. AB - The embryological development of the retroperitoneal venous system is a complex process. As a result, the anatomy of the inferior vena cava (IVC) and renal veins shows extensive variability. Improper completion of this process may lead to six anatomical variants: retroaortic left renal vein (LRV) types I and II, circumaortic venous collar, duplication of the IVC, transposition or left-sided IVC, and preaortic iliac confluence. All six are infrequent, but may be encountered during abdominal aortic reconstruction and pose challenging problems to the operating surgeon. Failure to appreciate these anomalies can lead to inadvertent injury and major venous bleeding. Preoperative diagnosis can be made on a CT scan, but this is not always performed prior to aortic surgery. In this report, we analyze two cases of retroaortic LRV complicating abdominal aortic aneurysmectomy, describe the most common infrarenal venous anomalies encountered during aortic surgery, and briefly review the literature. PMID- 11769157 TI - Spontaneous dissection of the abdominal aorta. AB - Spontaneous abdominal aortic dissection is a rare entity, often with a clinically unspecific presentation. The cause of the dissection is unclear. Angiography used to be the definitive diagnostic study, but today a correct diagnosis can be achieved with CT scanning and magnetic resonance angiography. The optimal form of management for the individual patient is not clearly established. Chronic dissections may best be managed conservatively, with close follow-up achieved with CT scanning and magnetic resonance. Acute and complicated dissections should be treated surgically with aortic and aortic branch replacement if it can be offered with low morbidity and mortality. In selected cases, resection of the ischemic organs may represent an alternative. PMID- 11769158 TI - Anterior spinal cord ischemia after infrainguinal bypass surgery. AB - Morbidity of infrainguinal bypass surgery is mostly related to cardiac complication, graft thrombosis, and wound infections. Neurologic complications in these patients are unusual and generally related to traumatic peripheral nerve injury or ischemia. Anterior spinal cord ischemia, manifest clinically as flaccid paraplegia or lower extremity paraparesis, is a complication usually associated with aortic surgery. Reported here is a case of an 81-year-old male who developed spinal cord ischemia after infrainguinal bypass under epidural anesthesia. PMID- 11769159 TI - Physician executives must leap with the frog. Accountability for safety and quality ultimately lie with the doctors in charge. AB - Take a look at how one New Jersey medical center is tackling The Leapfrog Group's mandates for change. Achieving the goals for better quality and high levels of patient safety requires diligence, patience and a strong willingness to change. PMID- 11769161 TI - Do you demonstrate leadership skills when you speak? AB - Nervous about your next big presentation? Don't be. There are proven ways to polish your presentation, spice up your speech and capture your audience's attention. Find out how experienced physician executives deliver dynamic presentations and learn tips for avoiding common mistakes. PMID- 11769160 TI - Philly physician executive combats big city blight. AB - Despite no money for college and little encouragement from his teachers, Eric Mitchell was determined to make something of himself. Ever since he got that plastic doctor kit when he was 7, he dreamed of becoming a physician. Learn how he achieved that goal--and so much more. PMID- 11769162 TI - Leaders as combat fighter pilots. Research project targets leaders who support money-losing business strategies. AB - When strategic plans go awry and begin losing money, the smart thing to do is change course. But some leaders get so involved with the plan, they fail to navigate properly and fly right into the target. The organization can lose millions. Examine why this happens and what you can do to prevent it from happening in your organization. PMID- 11769163 TI - Physician executive promotes process for managing change. Building consensus for group plan is key to successful transitions. AB - Thrust into a leadership position after years in solo practice demanded quick thinking for one physician executive. Faced with a need for change, he developed his own process for turning an individual's idea into a plan of action for an entire group. Learn the steps he took to build consensus and ease resistance to change. PMID- 11769164 TI - Cooperation, cost control and consumer focus are critical challenges for health care. AB - As we move into the 21st Century, the U.S. health care system faces tremendous challenges such as care for an aging and increasingly diverse population, escalating costs and limited resources. Government, consumers, hospitals and the insurance industry are positioning themselves for the future. Physicians need to do the same. Physicians must come to the table and assert leadership by working collaboratively with major stakeholders. Examine some steps that need to be taken to help shape the future of medicine. PMID- 11769165 TI - Palliative care programs: what, why, and how? AB - Establishing a palliative care service can improve patient care and ease family concerns for patients who are hopelessly ill. For the hospital, such services can improve utilization outcomes. Take a closer look at a palliative care service operating for nearly five years at Mount Sinai Hospital in New York City. PMID- 11769166 TI - New management opportunities and the Kentucky River case. AB - Physicians and other health care workers seeking to unionize may face an uphill battle as a result of a recent decision by the U.S. Supreme Court that essentially defines nurses and physicians as supervisory personnel who can't engage in collective bargaining. Discover what led to the decision and how it affects health care. PMID- 11769167 TI - New model helps find missing link between financial and clinical health care management. AB - U.S. health care is missing a link between the financial managers and clinical health managers of defined patient populations. Utilization and cost management try to bridge the gap by focusing on restricted access to care or tightly managed provider reimbursement to control costs. But frequently, they do not take clinical outcomes or health status into consideration. Take a look at another method based on the science of epidemiology that brings a more balanced knowledge of the clinical world to financial managers and more financial insight to clinicians. PMID- 11769168 TI - How to avoid common overhead allocation mistakes. AB - Paying for overhead in a physician practice can be tricky, especially when it comes to figuring out who pays for what. Examine some common overhead allocation errors and learn how to fix them. PMID- 11769169 TI - One giant leapfrog for health care. AB - Fed up with skyrocketing health insurance costs, poor quality care and low patient satisfaction, a group of powerful benefits executives from some of the country's largest employers decided to do something about it. They formed The Leapfrog Group, a coalition of companies setting out to build a better American health care system. PMID- 11769170 TI - Suturing an organization. AB - Before you fix the problem, enact great change or make a far-reaching decision, take time to notice, listen and get involved. These acts provide the best insight, the best treatment, to heal an organization's wounds. PMID- 11769171 TI - Change ability and I2: two keys to success in both new and old economies. PMID- 11769172 TI - Opportunities? Barriers? It's up to you. AB - This career advice column is usually directed toward those in transition- physician executives who are actively pursuing job opportunities or preparing to do so. But most of your career is actually spent in a position and on the job. So it seems appropriate to focus on the great majority of physician executives who are not currently in the job market. Take a look at opportunities to learn and grow in your present position. PMID- 11769173 TI - So doctor, you want to be an executive? Persistence pays off in physician's hunt for first management post. AB - Like a budding novelist hoping to sell that first manuscript, physicians trying to break into medical management may face many rejections. Read one physician's personal tale of perseverance that finally propelled him to the business side of medicine. PMID- 11769174 TI - Merger mania. What will a merger mean to you? AB - Almost as worrisome as job tenure to survivors of corporate mergers is whether they will be able to work under a completely new set of assumptions. What effect will the merger of two different corporate cultures have on effectiveness, satisfaction and promotability? Even people who believe they know the partner's culture almost as well as their own are often surprised at what happens after a merger takes place. Find out what's likely to happen in a merger by asking a few key questions. PMID- 11769175 TI - The Health Insurance Flexibility and Accountability (HIFA) Demonstration program. A new initiative to cover the uninsured. AB - Seeking to keep his promise to give states more flexibility while expanding health insurance coverage to low-income people, President George W. Bush released a proposal to reform Medicaid and The Children's Health Insurance Program. This initiative, the Health Insurance Flexibility and Accountability Act (HIFA), represents a significant change in Medicaid policy. Whether states will find this proposal a useful tool to expand coverage remains to be seen. PMID- 11769176 TI - [Criteria for evaluation of immunoblots using Borrelia afzelii, Borrelia garinii and Borrelia burgdorferi sensu stricto for diagnosis of Lyme borreliosis]. AB - The immunoblot was prepared from genotypes Borrelia afzelii (KC 90), Borrelia garinii (M 192) and Borrelia burgdorferi sensu stricto (B 31). Sera of 63 patients with different forms of Lyme borreliosis were examined and 40 healthy donors in the endemic area of the disease. In class IgM in the group of patients significantly more frequently antibodies against OspC, p39, p41 B. afzelii, p39, p41, p66, p83 B. garinii and OspC1, OspA, B. burgdorferi sensu stricto were found. In class IgG there were antibodies against p39, p41, p93 B. afzelii, p14, p41, p93 B. garinii and OspA, OspC p93 B. burgdorferi sensu lato. Based on the assembled results by means of discrimination analysis and logistic regression the most suitable combinations of antigens for evaluation of immunoblots in different genotypes were determined. Furthermore evaluation was suggested using a combination of antigens of several genotypes which led to an increased sensitivity and specificity of the immunoblot. Tables were prepared for easier evaluation of newly examined sera samples. PMID- 11769177 TI - [Human transmission of tuberculosis confirmed by DNA fingerprinting]. AB - By means of fingerprinting based on detection of the insertive sequence IS6110 v DNA of M. tuberculosis predigested by the restrictive enzyme PVUII the authors proved epidemiological associations in three patients with bacillary tuberculosis. The primary source of infection was a 44-year-old man, alcoholic and homeless suffering from tuberculosis diagnosed during an episode of ethylic ebriety, discharged prematurely from hospital because of lack of discipline and drunkenness who died after 8 months with a finding of caseous pneumonia. The first contact person was a 53-year-old women suffering from diabetes and hypertension, an auxiliary worker in the laboratory where she probably was infected during manipulation of the patients infected sputum. The other patients was a 49-year-old man, alcoholic, unemployed where a symptomatic tuberculous finding was detected with general weakness, elevated temperatures and expectoration, who most probably was infected by a patient during accidental contact in his domicile. The profiles of RFLP strains of M. tuberculosis of all three patients had an identical appearance of the DF-1 clone formed by seven copies of IS6110. This profile was not found in any of the total of 98 strains of M. tuberculosis examined within the framework of the molecular epidemiological prevalence study of patients with bacillary tuberculosis notified in Prague in 1999. PMID- 11769178 TI - [Luminescence analysis of respiratory burst in neutrophils using microtiter plates]. AB - The authors describe luminometric analysis of neutrophil respiratory burst in microtitre plates. They analyzed the neutrophil luminescence in small volumes of whole blood and in the so-called buffy coat (plasma with leucocytes after removal of erythrocytes by dextran sedimentation). To produce respiratory burst four types of activators were used: opsonized zymosan, phorbol myristate acetate, N formyl-Met-Leu-Phe and calcium ionophore A23187. It was revealed that the chemiluminescence response of neutrophils in whole blood and in the buffy coat is very similar in different types of activators, although the chemiluminescence activity of whole blood was always lower as compared with the buffy coat. This was probably due to an increased expression of cell receptors as a result of the separation procedure on the one hand and quenching properties of erythrocytes (haemoglobin) on the other hand. From the assembled results ensues that luminometric analysis in microtitre plates is a reliable protocol for assessment of the neutrophil respiratory burst, whereby assessment in whole blood should be preferred. PMID- 11769179 TI - [Endemic incidence of Mycobacterium kansasii infection in Karvina District 1968 1999; overview of the descriptive characteristics]. AB - The objective of the submitted work was to present a summary of basic epidemiological data in a group of 1034 subjects from whom during the period between 1968-1999 Mycobacterium kansasii was isolated. In the analysis of the group principles of the descriptive epidemiological method were used. In the first years, when diseases were recorded and the number of cases increased, epidemiologists of the District Hygiene Station in Karvina made an investigation. The objective was to describe the clinical aspect and based on epidemiological investigations to analyze data and to find an answer to basic links of the spread of infection, i.e. source, route of transmission to susceptible subjects and based on the assembled findings, to suggest the necessary epidemiological provisions. Interhuman transmission was not proved in any of the patients. The causal agent of the infection is most probably transmitted through water (by the aerogenic route). The Karvina district belongs to the largest investigated endemic areas in the world. PMID- 11769180 TI - Bush administration insists AIDS still a priority, despite bioterrorism. PMID- 11769182 TI - World Trade Organization debates patent rights for drugs. PMID- 11769181 TI - Survey: economic downturn, attacks worsen fiscal outlook. PMID- 11769183 TI - Medicaid. Tennessee appeals appointment of eligibility special master. PMID- 11769184 TI - HIV-positive status increases prison time for sex offender. PMID- 11769185 TI - Needle exchange. Conference committee to decide if D.C. can fund programs. PMID- 11769186 TI - Discrimination. Ohio jury awards $5 million to former McDonald's manager. PMID- 11769187 TI - AIDS patient burns himself: nursing home negligent. PMID- 11769188 TI - Conviction in AIDS-cure scheme results in 14-year sentence. PMID- 11769189 TI - Adoption. Jurors to decide if agency hid adopted child's HIV status. PMID- 11769190 TI - Colorado Medicaid told to consider hot tub funding request. PMID- 11769191 TI - Time limit for product claims applied to contaminated blood. PMID- 11769192 TI - Court finds company accommodated employee with AIDS. PMID- 11769193 TI - Lawsuit over liability coverage for AIDS-cure firm to proceed. PMID- 11769194 TI - Texas immune from lawsuit about medical information. PMID- 11769195 TI - [Evidence-based nursing care]. PMID- 11769196 TI - [Management of enteral feeding and nasogastric tubes]. PMID- 11769197 TI - [The placement of nasogastric tubes]. PMID- 11769198 TI - [Should bladder training be done before catheter removal?]. PMID- 11769199 TI - [Tracheobronchial suction]. PMID- 11769200 TI - [How to evaluate penicillin allergy?]. PMID- 11769201 TI - [Management of parenteral nutrition and central and peripheral venous catheters]. PMID- 11769202 TI - [What's new in intramuscular injection techniques?]. PMID- 11769203 TI - [Graduated compression stockings for the prevention of postoperative thromboembolism]. PMID- 11769204 TI - [Online resources for evidence based nursing care]. PMID- 11769205 TI - [World Trade Organization and General Agreement on Tariffs: politics of business and politics for health]. PMID- 11769206 TI - [Portrait of an artist with Alzheimer's disease]. PMID- 11769207 TI - Parents' and adolescents' perceptions of helpful and nonhelpful support for adolescents' assumption of diabetes management responsibility. AB - The study identified parents' and adolescents' perceptions of helpful and nonhelpful support, specific to adolescents' assumption of responsibility for diabetes management. Sixteen pairs of parents and adolescents with type 1 diabetes (11-18 years of age) were interviewed. The interviews were audiotaped and transcribed verbatim. Data were analyzed for manifest content according to social support dimensions identified by Barrera and Ainlay (1983). Inter-rater agreement between primary investigator and doctorally prepared diabetes nurse and educator was 100%. Both parents and adolescents describe directive guidance and tangible assistance as helpful and nonhelpful, depending on degree of directness and perceived need for help. Nurses can encourage parents to use subtle guidance and adolescents to communicate their needs. PMID- 11769208 TI - Sexual abuse, alcohol and other drug use, and suicidal behaviors in homeless adolescents. AB - Previous research has shown that homeless youth have high rates of suicidal ideation, sexual abuse, and abuse of alcohol and other drugs. However, little is known about how these rates differ by gender and ethnicity. Our objective was to describe patterns of sexual abuse, alcohol and other drug use, and indicators of suicidal behaviors in homeless adolescents and to determine gender and ethnic differences in these factors. We used secondary data analysis of data from surveys completed by 96 homeless youth whose average age was 17.9 years. Over 60% of the sample reported a history of sexual abuse; the majority were under the age of 12 years when they first tried alcohol, marijuana, and cocaine; 56.3% had injected drugs, and 46.9% had tried inhalants. During the past 12 months, 35.1% had seriously considered suicide and 12.3% had actually attempted suicide at least once. Significantly more Hispanics than Whites had considered suicide (chi 2 = 4.31, p = .038). A disproportionate number of Hispanics (95% of the sample) reported a history of sexual abuse. Participants with a history of sexual abuse were significantly more likely than those who did not have a history of sexual abuse to have used alcohol and/or marijuana (chi 2 = 9.93, p < .01) and to have considered suicide in the past 12 months (F = 14.93, p < .001). We found that sexual abuse history is greater in this sample than in the general population and is particularly prevalent among Hispanic/Latino subjects. As in other studies, sexual abuse was more common among females than among males. High prevalence of sexual abuse, alcohol and other drug use, and suicidal behaviors in this sample of homeless youth underscores the need to develop and test community-based interventions to improve their health status. PMID- 11769209 TI - Balancing recruitment and protection: children as research subjects. AB - Since 1994, federal guidelines for research in the United States have called for the inclusion of special populations, among them, children, in clinical research (National Institutes of Health, 1998). While the guidelines are intended to assure the fair distribution of research benefits to children, this federal mandate has created an ethical dilemma for researchers. Health professionals involved in research with children are called on to balance improving access and recruitment of children for clinical trials with the need to protect this very vulnerable population. Given this balancing act, it is important for nurse researchers to be familiar with the issues of informed consent and assent with children. Our article reviews instances of exploitation of children in research, laws and federal regulations on informed consent and assent designed to protect children, and research on factors that affect children's capacity to consent/assent. We conclude with recommendations to assure a proper balance between the need to recruit children into clinical trials and the need to protect their rights as human subjects. PMID- 11769210 TI - "Camping up" self-esteem in children with hemophilia. AB - Children with hemophilia have often been viewed at greater risk for altered self esteem than their healthy counterparts. Our article shares the positive effects of the camp experience on children with hemophilia and subsequent enhancement of self-esteem. Interaction and support in the camp environment provide an opportunity for these children to gain independence and "prove" their self-worth and ability. Previous literature has provided a variety of findings on the relationship between chronic illness, such as hemophilia, and self-esteem alterations. We identify many opportunities for future education and research to provide quality nursing support to this unique population. PMID- 11769211 TI - [Motor vehicle source contributions to air pollutants in Beijing]. AB - Beijing's motor vehicle emission inventory based on GIS technology was developed, and used to estimate the contribution rate of different types of vehicles and different areas of vehicles to the total vehicular emissions in the urban area of Beijing. ISCST3, a gaussian dispersion air quality model, was modified at low wind speed condition, and then used to facilitate the study of the spatial and temporal distribution of CO and NOx concentrations in Beijing. It was shown that vehicle source emissions of CO and NOx accounted for 76.8% and 40.2%, respectively, of the total emissions in 1995. The simulation results also showed that emissions from the vehicle sources had contributed 76.5% and 68.4% of the total CO and NOx concentrations in urban atmosphere of Beijing in 1995, and were even higher at down-town and near the arteries. Therefore, strategies for CO and NOx pollution control will of necessity need to focus on the vehicle sources. PMID- 11769212 TI - [Ultrasonic removal of organic pollutants in tannery waste water]. AB - The effect of ultrasonic treatment on flocculating settling of tannery effluent was studied, removal of COD in particular was did. The influences of irradiation method and duration of ultrasonic as well prescription of coagulants on the efficiency of minimizing organic chemicals in waste water were investigated. The results show that: 1. when waste water was treated only by ultrasonic for 60s, the removal rate of COD was 40.6%; 2. when total concentration of coagulants increased to 100 mg/L, the highest removal rate of COD was achieved; 3. when waste water was firstly treated with ultrasonic for 60s, then flocculated with coagulants, the removal rate of COD came to 73.2%, 10% higher than the control without ultrasonic. Thus the treatment of tannery waste water with flocculating settling technology can be effectively strengthened by ultrasonic. PMID- 11769213 TI - [Autotrophic ammonium-removal of sludge liquor]. AB - The autotrophic ammonium-removal process was realized in floating bed reactors with sludge liquor as substrate. Biofilm of autotrophic bacteria were formed on the surface of carriers in reactors. The main operation conditions of the reactors were as the following: T = 28 degrees C, pH = 8.0 and DO = 0.8-1.0 mg/L. The average surface load of two reactors in series was NH4(+)-N 3-4 g/(m2.d), and the general autotrophic ammonium-removal efficiency was about 70%. The Autotrophic ammonium-removal technology promises considerable savings in regard to the oxygen consumption and external organic carbon addition compared with the conventional nitrification-denitrification technology when it was used to treat ammonium-rich and unfavourable C/N ratio wastewater. PMID- 11769214 TI - [Effect of lead stress on the activity of antioxidant enzymes in wheat seedling]. AB - The changes of the antioxidant enzyme activity, such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were researched through nutrient solution culture. The results showed that the activity of SOD in shoot and root were significantly enhanced under lead stress. The activity of CAT in root was also improved, but the degree was not bigger than that of SOD activity. However, the MDA content in shoot and root was significantly higher than that of check group, it suggested that the membrane system were damaged by lead stress. The experiments also revealed that the shoot of wheat seedling was influenced by lead stress greatly stronger than that of root. PMID- 11769215 TI - [Bioslurry remediation of soil contaminated with polycyclic aromatic hydrocarbons]. AB - Through the operation of the pilot-scale slurry reactor, the operational parameters of bioslurry remediation for soil contaminated with polycyclic aromatic hydrocarbons(PAHs), including temperature, ratio of water to soil, aeration flux, were determined. As the operational condition was that the ratio of water to soil was 2:1, the temperature was 20 degrees C-25 degrees C and aeration flux was 60 L/h, a good result of the remediation could be achieved. With the fungi isolated from contaminated soil as pure culture to degrade PAHs, after 34 days incubation, 90% of pyrene and 33.3% of benz[a]anthracene were degraded by Fusarium, 81.5% of pyrene and 49.2% of benz[a]anthracene were degraded by Mucor, 52% of pyrene and of 46% of benz[a]anthracene were degraded by Penicillium. PMID- 11769216 TI - [The transferability of acetochlor and butachlor in soil]. AB - The transferability of acetochlor and butachlor in soil was studied by soil thin layer chromatography. Acetochlor and butachlor were dropped on the glass plate and spreaded soil on the glass plate was collected per 2 cm, then acetochlor and butachlor were analyzed quantitatively by HPlC. When river water was as the spread solution, Rf(relative flow) of acetochlor and butachlor in the Haidian loam were 0.116 and 0.031 respectively, Rf of acetochlor and butachlor in the Baiyangdian sandy loam were 0.147 and 0.032 respectively. When 30 mg.L-1 dodecylbenzene sulfonic acid sodium salt solution was as the spread solution, Rf of acetochlor and butachlor in the Haidian loam were 0.159 and 0.034 respectively. Acetochlor's transferability was weak and the gradation of its transferability was II grade, while butachlor's was more weak and the gradation was I grade. Anionic surfactant solution can promote pesticides to transfer. Cationic surfactant solution can impede pesticides to transfer. PMID- 11769217 TI - [Purification feasibility of malodorous waste gas contained H2S and CS2 by DBD technique]. AB - Dielectric barrier discharge(DBD) technique was applied to remove H2S and CS2 in industrial waste gas. In the research of laboratory, when the voltage between two electrodes was 12 kV, 4 x 10(3) Pa H2S was discharged in air for 5 seconds, about 100% of H2S was transformed into H2O and SO2; 1.33 x 10(3) Pa CS2 was discharged in air for 15 seconds, about 80% of CS2 was transformed into CO2, CO and SO2. When the concentration of H2S and CS2 increased, the decomposition of them decreased. Based on the results, a DBD purification apparatus which can dispose 420 m3/h, 10 m/s waste gas was designed and manufactured, the removal rate of H2S can reach 89% and the energy consumption was 5.2 W.h/m3. It was concluded that the DBD technique is worth disposing malodorous industrial waste gases contained H2S and CS2. PMID- 11769218 TI - [Composting process of municipal solid waste with high effective complex microbial community]. AB - The effects of high effective complex microbial community (MECMC) in a combination composting process of municipal solid waste (MSW) and sludge were examined through inspecting biomass, temperature, organic matter, the carbon, nitrogen ration (C/N). Composting was performed under such conditions: The ratio of MSW:sewage:sawdust:composting of 45:25:15:15 (W/W) and organic matter of 60%, total N of 1.4%, total P of 0.69%, total K of 1.25%, original moisture of 58.5%, original ratio of C/N of 30, aration flow of 0.8 L/min.kg(volatile organic matter). The rates of adding HECMC to treatment 1, treatment 2 and treatment 3 were 2%, 3%, 5% respectively. Control experiment added 3% inactive HECMC. The day of MSW and sludge mature in control experiment, treatment 1, treatment 2 and treatment 3 were 30, 24, 18 and 12, respectivly. This indicated HECMC were effective to compose organic matter and speedup composting change into humus. There are many active bacteria in composting which are favorable for soil. PMID- 11769219 TI - [A simple and rapid procedure for detection of DNA damage caused by Aldicarb]. AB - A simple and rapid procedure for detection of low levels DNA damage caused by Aldicarb was developed and compared with some other methods. In the original position the gel was set in high-pH buffer to run electrophoresis after the diluent of bacteria or fragmentized organ was added into hole of agarose gel directly and cells were treated with detergent and high alkaline condition. The impact of Aldicarb to biological individual or ecosystem was assessed according to the quantity of DNA and the extent of DNA migration. PMID- 11769220 TI - [Catalytic reduction of NO by chars loaded with Ca and Fe]. AB - The effects of calcium and iron impregnated on coal chars as catalysts in NO-char reaction were investigated. The NO-char reaction was studied in a quartz fixed bed reactor at atmospheric pressure. Temperature programmed reaction (TPR) and isothermal reaction were used to determine the catalytic activities of calcium and iron at various atmosphere environments. The results showed that the higher the temperatures of pretreatment, the lower the catalytic activity of calcium, while the pretreatment temperatures had little effect on the catalytic activity of iron. Both calcium and iron promoted the NO-char reaction, but the catalytic activity of the latter was higher than that of the former. NO reduction by CO was strongly promoted by Fe and Ca. The addition of O2 in the char-NO-Ca or char-NO Fe system promoted the NO reduction significantly. Oxidation/reduction mechanisms were proposed for the NO reduction by char catalyzed by Ca and Fe. PMID- 11769221 TI - [Emission of volatile sulfur gases from Chinese paddy soils]. AB - In the paper, emission of volatile sulfur gases from paddy soil was discussed in a growth period of paddy rice by constructing a field sampling system. The result showed that COS, CS2, DMS and DMDS were mainly emitted from paddy soil. The order of emission fluxes was 81.11, 6.33 and 10.71 mg.(m2.a)-1. Sulphur emission fluxes of Chinese paddy soil was 0.013662 Tg/a, and those of world paddy soil was 0.07992 Tg/a. PMID- 11769222 TI - [Acidity and acid buffering capacity of aerosols during sand-dust storm weather in Beijing]. AB - In the spring of 2000, there were 12 sand-dust storms in Beijing. 2 sand-dust storms were experienced in time and mass concentrations, elementary concentrations acidity and acidic buffering capacity of TSP(Total Suspended Particulate, < 100 microns) and PM10(Inhalable particulate, < 10 microns) were sampled and analyzed. Results showed that pollution level of aerosols was extremely high. However, the acidity of aerosols was relatively low and the aerosols had very strong acid buffering capacity for acidification. Therefore, the aerosols brought about by the sand-dust storms could avoid the occurrence of acidic precipitation to some extent. PMID- 11769223 TI - [A method of desulfurization with calcium sulfite and it's mechanism]. AB - Directing to the scaling problem lying in wet desulfurization with lime slurry, a method of desulfurization with calcium sulfite was proposed. Reaction mechanism and the effects of different conditions on desulfurization efficiency were studied. The optimum conditions were obtained, i.e. air velocity of 2.75 m/s in empty tower, L/G = 3.0 L/m3, solid content 6.7%, air temperature 31 degrees C, concentration inlet of SO2 1500 x 10(-6) and inlet suspension pH of 8.0. Under the conditions, the desulfurization efficiency was about 87%. The presented method theoretically and practically solved the scaling problems, which is a novel indirect lime-method with Ca-contained material as desulfurization agent. PMID- 11769224 TI - [Major inorganic compositions in fine and coarse particles of ambient aerosol at Qingdao]. AB - Four times measurements of ambient aerosol were conducted from September, 1997 to August, 1998 at a coastal site of Qingdao. The results indicated that mass concentrations of aerosol mainly exist in fine particles(PM2.5, diameter less than 2.5 microns). The proportion of the fine particles in the heating period is much higher than that in the non-heating period. SO4(2-), NH4+, NO3-, K+ mainly exist in the fine particles while Na+, Cl-, Mg2+, Ca2+ mainly exist in the coarse particle, F-, Cl-, Br- mainly exist in the fine particles in the winter, but in the coarse particles in the summer, which reflects the influence of anthropogenic burning source and atmosphere temperature. PMID- 11769225 TI - [The influence factors of SO2 removal in flue gas with a pulsed corona discharge]. AB - The influence of the operation parameters on SO2 removal rate with a pulsed corona discharge was studied in this paper, in order to promote the industrial applications of this technology. The flow rate of the flue gas was 1000-3000 m3/h. The SO2 removal rate reached 80%. The range of SO2 concentration in flue gas was 1000-2000 ml/m3. The flue gas temperature was 60 degrees C-80 degrees C. The molecule ratio of NH3 to SO2 was 2. The energy consumption was 3-5 W.h/Nm3. The wire-plane electrode structure and a positive high voltage pulse power supply were used in the experiment. PMID- 11769226 TI - [Anaerobic hydrolysis of terramycin crystallizing mother solution]. AB - The terramycin crystallizing mother solution contained high organics and high nitrogen. There were many kinds of bioinhibition in it but not enough electronic donor. Anaerobic hydrolysis of terramycin crystallizing mother solution was completed with up anarobic sludge bed in order to improve the biodegradability of wastewater and electronic donor in it. The variations of pH, COD, NH4+, and SO4(2 ) were monitored. The COD removal was in a narrow range between 10% and 16.4% even when the HRT of the reactor was changed from 1.5 h to 6 h. pH increased because of formation of NH3 and reduction of SO4(2-). Most of SO4(2-) was reduced to S2- when the HRT was longer than 2 h. Batch experiments on hydrolyzed wastewater demonstrated that reaction rates of nitrification and denitrification increased by 90.9% and 45.2%, respectively. PMID- 11769227 TI - [The influence of hydraulic characteristics on wastewater purifying efficiency in vertical flow constructed wetlands]. AB - The hydraulic characteristics of vertical flow constructed wetlands was investigated, and the influence of these characteristics on wastewater purifying efficiency was studied as an emphasis. The results of the experiments in small scale plots and medium scale plots showed the plant roots, with the physical and biological effects, play a significant role in hydraulics and the wastewater purifying efficiency. The other characteristics such as retention time, effluent velocity and influent load also directly affect the wastewater purifying efficiency of constructed wetland. To get a better understanding of the hydraulics will be crucial to the improvement of purifying efficiency and facilitate the practical use of constructed wetland. PMID- 11769228 TI - [Start-up of full-scale UASB reactors]. AB - The UASB reactors treating high-temperature citric acid wastewater could be started up in the alternation of mesophilic and thermophilic ranges because the local climate changed greatly by seasons. The reactors were started up in mesophilic range, and the total efficiency of the two-stage reactors reached 77% 86%; when the temperature of reactors reached 44 degrees C-45 degrees C, the reactors were operated in thermophilic range, and the total efficiency of the two stage reactors reached 84%-93%; the reactors were re-operated in mesophilic range after closing about 38 days, and the total efficiency of the two-stage reactors reached 82%-96%. The start-up in the alternation of mesophilic and thermophilic ranges of the full-scale UASB reactors and the characteristics of mesophilic and thermophilic granular sludge were reported in this paper. PMID- 11769229 TI - [Repetitious sorption of phenol to organobentonites from water]. AB - The properties and mechanisms for repetitious sorption of phenol to organobentonites from water were studied. Results showed that organobentonites could be used to sorb phenol from water many times with high removal rates. The sorption capacities of three single-cation organobentonites were 120 CTMAB bentonites > 120 CPC-bentonites > 120 DTMAB-bentonites, when the original concentration of phenol was 1000 mg/L. The sorption mechanisms changed from adsorption to partition in the process of repetitious sorption. Sorption of phenol to CPC-bentonites could bring synergic sorption. The distribution coefficience (Kp) were related to the quantities of phenol on CPC-bentonites, while the distribution coefficience of phenol on CTMAB-bentonites and DTMAB bentonite were constant. PMID- 11769230 TI - [Characteristics of nitrobenzene containing wastewater catalytic oxidation degradation by Fenton reagent]. AB - Through the alteration of the concentration of catalyst and oxidant, the rulers and dynamics of nitrobenzene oxidized by Fenton reagent in different concentrations were studied. The correlativity of the reaction time and relatively remain nitrobenzene was analyzed by the unitary linear regress equation. The result of the analysis proves that the coefficient was over the critical constant. The oxidation of nitrobenzene by Fenton reagent was in conformity with first-order dynamics model and the reaction rate constant was got at the same time. The idea, using the complex of Fe as the catalyst replacing Fe2+ in the Fenton Reaction, not only got a higher reaction velocity and efficiency, but also had a distinct exclusive to the degradation of nitrobenzene. The remove velocity of nitrobenzene was improved from 17.48 mg/(L.min) to 71.22 mg/(L.min), the remove rate in 5 minutes was from 9.74% to 91.79%. The nonhomogeneous catalyst made by the artificial zeolite with Fe-complex adsorbed had the same catalyzing behavior. In addition, ultraviolet radiation can also improves the Fenton reaction to some degree. These research works could demonstrate the good application potentiality of Fenton reagent in treating wastewater. PMID- 11769231 TI - [Adsorption of weak deep blue GR on hydroxy-aluminum montmorillonite]. AB - Hydroxy-alumium montmorillonite may serve as potential adsorbents for organic pollutants from wastewater. It was synthesized by titrating Na-montmorillonite with hydroxy-aluminum solution (OH-/Al3+ molar ratio was 2.4). From powder XRD data, it was shown that the interlayer(d001) of montmorillonite was increased greatly from 12.58A to 18.63A. Seven modified montmorillonite samples, including hydroxy-aluminum montmorillonite, were used to remove the dye of weak deep blue GR from water. The results showed that hydroxy-alumium montmorillonite had very high adsorption ability, only 0.0200 g could treat 25 ml weak deep GR with 95% removal. The different adsorption mechanisms of weak deep blue GR on modified montmorillonite: surface adsorption, ion-exchanging and partion, were suggested. PMID- 11769232 TI - [N2O emission by trees under natural condition]. AB - The sources of N2O, one of the major greenhouse gases in the atmosphere, are still unclear till now. It was previously thought that only soil microbial process produced N2O. The aim of this study was to provide evidences that plant can emit N2O under the natural condition. The measurement of aboveground vertical profiles of N2O concentrations were conducted within coniferous-deciduous mixed forests in Changbai Mountain, China. Significant high N2O concentrations were found at or near the height of canopy. High concentrations in profiles were 3.03% to 64.9% higher than the "normal concentrations". Differences between the high concentrations and the "normal concentrations" were statistically significant. The simultaneous occurrence of high concentrations at/nearby the canopy height and normal concentrations at the trunk space height indicated an efflux of N2O from foliage to atmosphere. This study afforded evidences supporting that plant per se, besides forest soil, was an important source of atmospheric N2O in a forest ecosystem. PMID- 11769233 TI - [Landfill leachate treatment by anaerobic process and electrochemical oxidation]. AB - This study was conducted to develop a two-stage process of UASB and electrochemical oxidation for the treatment of Hong Kong leachate. The leachate, containing 4750 mg/L of chemical oxygen demand (COD) and 1310 mg/L of ammoniacal nitrogen (NH3-N), was first treated in a UASB (upflow anaerobic sludge blanket) reactor at 37 degrees C. The process removed on average 66% of COD with 6.1 days of hydraulic retention time (HRT), corresponding to an organic loading rate COD of 0.78 g/(L.d). The UASB effluent, which had an average pH of 8.9, COD of 1610 mg/L and NH3-N of 1480 mg/L, was then further treated by electrochemical oxidation in a batch reactor with recirculation. With the addition of 2000 mg/L of chloride (in the form of sodium chloride) and at a current density of 32.3 mA/cm2, 87% of COD and 100% of NH3-N were removed from the UASB effluent in six hours. The energy consumption was < 55 kW.h/kg COD. The final effluent contained no residual NH3-N and only 209 mg/L of COD. In this paper, some basic problems in electrochemical oxidation, such as the effects of the operation parameters, the mechanism of the process, and assessment of the energy requirements were discussed in detail. PMID- 11769234 TI - [Recovery of zinc ion and cadmium ion with hollow fiber membrane extraction]. AB - The efficiency of hollow fiber membrane solvent extraction for the system of Meaq/bis(2-ethylhexyl) phosphate in heptane(Me = Cd2+, Zn2+) was studied for wastewater treatment and hydrometallurgy. It was found that the two phases velocity, the initial concentration and the pH value of the aqueous phase greatly influenced the extraction ratio. For very dilute solution with concentration lower than 500 mg/L, the mass transfer resistance was mainly in aqueous phase. When the aqueous phase concentration was relative higher than that of dilute solution, all the individual mass transfer resistances would not be ignored. For the concentrated solution, the mass transfer in the organic phase and the diffusion in membrane pores controlled the transport process. In the back extraction, the mass transfer resistance lied in the organic phase and the diffusion in membrane pores. The experimental results showed that it was possible that the extraction percentage achieved 90% when the metal ion concentration was lower than 400 mg/L. When the cadmium concentration was lower than 200 mg/L, its concentration can decrease 2 orders by extraction in a single-pass flow mode. The values of (HTU)w were between 15 cm and 30 cm, which was much lower than those of traditional extraction columns. The results indicated that membrane extraction with hollow fiber modules could efficiently remove or recover metal ions in the aqueous phases. PMID- 11769235 TI - [Pretreatment of benzoic acid wastewater]. AB - The benzoic acid wastewater produced from toluene by liquid-phase oxidation is one of the difficult wastewater to treat because of multi-component, high CODcr value (20,000-100,000 mg/L) and nonbiodegradability. A pretreatment way of this wastewater by extraction based on chemical complexation was carried out, and tributyl phosphate (TBP), trialkylamine (7301) and trialkyphosphine oxide (TRPO) were used as complexing agent with n-octanol, kerosene as cosolvent and diluent respectively. Results showed that benzoic acid was recovery successfully and the CODcr value of wastewater was reduced to 1/6 of the initial value through multi stages cross-flow extraction. Back-extraction was quite easy and the solvent could be reused. PMID- 11769236 TI - [The application of air-lift loop column filling with porous carrier in wastewater treatment]. AB - An air lift loop reactor filling with porous carrier particles was utilized as aeration column. Experiments were carried out in wide operating conditions. The experimental results showed that in the range of gas flow rate from 0.117 to 0.156 m3/(min.m3), a higher efficiency of removal of ammonium-N was achieved, and when the gas flow rate was above 0.039 m3/(min.m3), the COD was completely degraded in about 1 h. The filling ratio of the porous carriers in the column was an important factor for the removal of C and N compounds, and a filling ratio of 15% was proved to be most suitable in the operation ranges. The experimental results also indicated that the effect of aeration temperature on the removal efficiency was significant and the highest efficiency was obtained at around 25 degrees C. PMID- 11769237 TI - [Sulfa-drug wastewater treatment with anaerobic/aerobic process]. AB - Sulfa drug wastewater was treated with anaerobic/aerobic process. The removal ratios of TOC reached about 50% in anaerobic phase and about 70% in aerobic phase respectively, while volume loading rate of TOC was about 1.2 kg/(m3.d) in anaerobic phase and about 0.6 kg/(m3.d) in aerobic phase. Removal of TOC in anaerobic phase was attributed to the reduction of sulfate. PMID- 11769238 TI - [The accuracy analysis on Kriging estimation of the water quality parameters of lakes]. AB - The spatial distribution of pollutants in lakes is required in the study of lakes. The key issue is the spatial optimal estimation. This paper elaborated the characteristics of Kriging variance and analyzed systematically the accuracy of Kriging estimation on water quality parameters of lakes in the light of a practical example of Taihu Lake. The accuracy of estimation was determined by many factors such as variogram, distribution of sampling sites and so on, and was not related to the values of sampling data. PMID- 11769239 TI - [Optimization of synthetic culture condition on lignin biodegradation ability of alkaliphilic ligninolytic bacteria using orthogonal experimental design]. AB - The effects of seven single culture factors on lignin biodegradation ability of alkaliphilic ligninolytic bacteria strain 6 in alkaline liquid medium (pH approximately 10.5) with compounded carbons were optimized using orthogonal experiments. The result showed the seven single culture factors promote the activities of Laccase and MnP and the degradation rate of wheat straw lignin in varying degrees. The synthetic result was analysised. The optimal synthetic condition was static culture (10 days culture period), 37 degrees C, the initial pH10.6, 1 g/L sugar (the starting carbons), wheat straw lignin (the second carbons, wheat straw powder 20 g/L, added into on the fourth day after inoculation), 1.2 g/L NH4NO3 (nitrogen), 0.3% detergent T-80, 70 ml medium/250 ml flask. PMID- 11769240 TI - [Degradation of nitrobenzene in water by electrohydrodynamic DC discharge]. AB - In this paper, the experimental results with respect to the degradation of nitrobenzene in water using electrohydrodynamic DC discharge were presented. The DC voltage was 40 kV, the degradation efficiency in the first discharge process reached 50%, the total degradation efficiency in the second discharge process reached 80%. The products contained acetone. At the same time, the degradation efficiency variation with the voltage polarity, flux, and concentration were studied. These studies will be helpful to the treatment of organic wastewater. PMID- 11769241 TI - "Toxic cyanobacteria--towards a global perspective," Fifth International Conference on Toxic Cyanobacteria, Noosa, Queensland, Australia, July 15-20, 2001. Proceedings. AB - ICTC-V was a highly successful conference, from both a scientific and a cultural perspective. Much robust debate was generated in an environment of good will and shared experience. The expansion of scientific and government interest throughout many emerging countries is heartening and significant. The new cyanobacterial species and, in some cases, new cyanotoxins, being reported in these countries, many of which are in the tropics and arid zones of the world, are enhancing the richness and quality of the global research effort on toxic cyanobacteria. The selected articles on toxic cyanobacteria published in this special edition of Environmental Toxicology provide just a few examples of the quality and breadth of work that is currently being undertaken throughout the world. PMID- 11769242 TI - Phenotypical variation in a toxic strain of the phytoplankter, Cylindrospermopsis raciborskii (Nostocales, Cyanophyceae) during batch culture. AB - A nonaxenic strain of Cylindrospermopsis raciborskii Woloszynska (AWT 205) was grown in batch culture, with and without nitrate as the primary N source. Rapid log-phase growth with nitrate was 1.0 doubling/day versus 0.3 doubling/day without nitrate. Cylindrospermopsin (CYN) production was measured by HPLC. The rate of intracellular CYN production matched cell division rate for both the diazotrophies at cell densities less than 10(7) cell/ml. At cell density > 10(7) cell/ml, additional resource limitation in batch culture slowed log-phase growth to 0.04 division/day and cell division and CYN production decoupled. Intracellular CYN concentration increased at a rate of 0.08 doubling/day, twice the cell division rate. Extracellular CYN as a proportion of the total CYN increased from 20% during the rapid growth phase, to 50% during the slow growth phase. The total CYN yield from cultures grown out to stationary phase (55 days) exceeded 2 mg CYN/I. C. raciborskii cells in log-phase growth, exposed to 1 ppm copper (as copper sulphate), lysed within 24 hours. After copper treatment, all CYN was in the filterable fraction. These findings imply that in naturally occurring blooms of C. raciborskii, the movement of intracellular CYN into solution will be the greatest during stationary phase, when intracellular concentrations are highest and cell lysis is more frequent. The application of algicides that promote cell lysis will exacerbate this effect. PMID- 11769243 TI - Nodularin uptake by seafood during a cyanobacterial bloom. AB - The problem of blue-green algal toxin contamination of recreational waters and drinking water catchments is well described, as is the potential contamination of associated seafood. Algal contamination of Victorian waterways is now a widespread annual occurrence and, in some regions, the intersection of blooms and commercial fishing threatens the food safety of large numbers of people. Toxin levels which produce no observed adverse effect in animal studies were used to derive safe tolerable daily intake levels. These 'acceptable levels' were then modified to protect against potential acute health risks associated with short term exposures. National food surveys were used to derive likely seafood intakes and thus, in combination with 'safe toxin levels', health alert levels for seafood were formulated. During the summer of 2001 a bloom of Nodularia spumigena occurred in the Gippsland Lakes area of Southern Victoria. During the bloom, seafood samples were collected and nodularin concentrations were estimated. Nodularin concentrations reached levels of concern in mussels and in prawn viscera at cell counts as low as 30,000 cells/ml. Nodularin concentrations in the flesh of finfish remained low. Boiling the seafood redistributed toxin between viscera and flesh. The results were used to restrict some seafood harvesting. PMID- 11769244 TI - Identification of cyanobacteria and their toxigenicity in environmental samples by rapid molecular analysis. AB - We report molecular analyses which identify cyanobacterial strains present in environmental samples. These analyses do not require the isolation and culture of strains. Identification of cyanobacteria used the polymerase chain reaction (PCR), based on the phycocyanin operon. Differentiation was either by restriction endonuclease digestion (restriction fragment length polymorphisms) or sequencing of the PCR products. Identification was based on sequence homology of the intergenic spacer region (IGS) between the beta- and alpha-phycocyanin subunits (PC-IGS) with database records. We have found that the length and sequence of the PC-IGS is capable of predicting the genus accurately, but not the species. Toxigenicity was determined with oligonucleotide probes for key steps in the microcystin toxin synthesis pathway. We have shown that it is possible to easily and routinely obtain PCR amplification products and differentiate the strains in bloom samples. The methods can detect even minor components in bloom samples, which may not be apparent on microscopic examination. Genetic probes for microcystin toxigenicity are effective on environmental samples, eliminating the need for isolation and culture of the organisms. The use of a suite of tests described here will allow water managers to determine the presence and the type of cyanobacteria and their microcystin toxigenicity. PMID- 11769245 TI - Presence of Planktothrix sp. and cyanobacterial toxins in Lake Ammersee, Germany and their impact on whitefish (Coregonus lavaretus L.). AB - Due to the increasing oligotrophy of Lake Ammersee, southern Germany, metalimnic Planktothrix have become one of the dominant planktonic species causing regular blooms. Whitefish (Coregonus lavaretus) is the dominant local fish species with great importance for the fishing industry. Recently, whole age groups of this fish species have disappeared and since 1991, average body-weight has decreased. The causes for this remain unclear. Planktothrix species produce the cyclic peptide toxin desmethyl microcystin-RR, which inhibits glycogen metabolism and has detrimental effects on the development of aquatic organisms. During blooms, gut contents of whitefish displayed a blue discoloration, possibly representing phycobiliproteins typical for cyanobacteria. This study aimed to elucidate the impact of Planktothrix blooms on fish population dynamics. Planktothrix cell counts, performed by epifluorescence microscopy, showed blooms to contain up to 80,000 cells/ml. Microcystin levels of 1-5 micrograms/mg dry weight in Planktothrix extracts and 0.08 microgram/l in water samples, were determined via HPLC and protein-phosphatase inhibition assay. Planktothrix filaments were detected in gut contents of whitefish. In addition, microcystins could be detected in gut contents via ELISA. Similarly, immunoprobing with microcystin antibodies demonstrated microcystin-protein adducts in liver homogenates of whitefish caught during Planktothrix blooms. Furthermore, Planktothrix extracts proved cytotoxic to trout hepatocytes as determined by MTT reduction. Whitefish eggs and larvae, obtained during blooms in winter 1998 and 2000 in a Lake Ammersee hatchery, were studied for developmental progress. Malformations typical for cyanobacterial toxin exposure were observed. PMID- 11769246 TI - The effects of the ciliate Paramecium cf. caudatum Ehrenberg on toxin producing Cylindrospermopsis isolated from the Fitzroy River, Australia. AB - The large ciliate Paramecium cf. caudatum Ehrenberg was found to be a successful grazer of toxin producing Cylindrospermopsis in the laboratory. The feeding rate increased with increasing cell concentration to 1367 cell animal hr-1 at 4.1 x 10(5) cells mL-1 but declined slightly at cell concentrations greater than this. Preliminary studies on the effects of this grazing on toxin concentrations in cultures of both straight and coiled forms of Cylindrospermopsis resulted in the production of different amounts of the toxin cylindrospermopsin in the different isolates. Differences in toxin production were also found between cultured and field populations from the lower Fitzroy River indicating that toxin production may be influenced by a suite of genetic and environmental factors. The proven ability of this ciliate to graze toxic Cylindrospermopsis provides some insight into interactions that may be able to control some toxic blooms in semiarid Australian conditions. PMID- 11769247 TI - Distribution of 14C cylindrospermopsin in vivo in the mouse. AB - Radiolabelled 14C cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SD) urinary and faecal recoveries (cumulative) were obtained, respectively: (0-6 hours, n = 4) 48.2 (29.3)%, 11.9 (21.4)%; (0-12 hours, n = 12) 66.0 (27.1)%, 5.7 (5.6)%; (0-24 hours, n = 12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n = 4), at 48 hours 13.1 (7.7)% (n = 8), and 5-7 days were 2.1 (2.1)% (n = 8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. PMID- 11769248 TI - Preliminary evidence of toxicity associated with the benthic cyanobacterium Phormidium in South Australia. AB - In April 2000, the water supply for Yorke Peninsula in South Australia was deemed non-potable when extracts from a proliferation of the benthic cyanobacterium Phormidium aff. formosum in Upper Paskeville Reservoir were found to be lethally toxic by intraperitoneal injection into mice (400 mg kg-1). Routine water quality monitoring had failed to detect the development of the Phormidium until complaints of musty taste and odour, attributable to the production of 2-methyl isoborneol (MIB), were received from the consumers. The 185 ML open-balancing storage, receiving filtered and chloraminated water from the River Murray, was isolated from the drinking water supply and a health alert was issued to approximately 15,000 consumers. The identity of the toxin(s) is thus far unknown, but clinical symptoms of toxicity in mice and chemical characteristics are distinct from the known major cyanotoxins. Preliminary characterisation of this toxin indicates that it has low solubility in water and organic solvents and is strongly associated with the particulate cellular material of the filaments. Toxicity of extracts was diminished by boiling and by treatment with chlorine, but not by chloramines. Further testing of floating cyanobacterial mats in the Torrens Lake in the city of Adelaide (Phormidium aff. formosum) and Myponga Reservoir (Phormidium aff. amoenum) in 2000/2001 was also found to be toxic by mouse bioassay. Toxicity is yet to be confirmed in monospecific cultured strains and further studies are required to identify the toxin and assess its health significance. Genetic characterisation of isolates has commenced in an attempt to classify their relatedness and to assist in the rapid identification of potentially toxic strains. PMID- 11769249 TI - Allergenic (sensitization, skin and eye irritation) effects of freshwater cyanobacteria--experimental evidence. AB - Many studies have been published on the human health effects of cyanobacterial toxicity. As a public health concern, we have to mention that the development of contact dermatitis, asthmalike symptoms, and symptoms resembling hay fever during bathing in cyanobacterial blooms have been also described. Microcystis aeruginosa, Anabaena flos-aquae, Aphanizomenon flos-aquae, and Cylindrospermopsis raciborskii are the most common species found in Hungarian freshwaters. A sensitization test on albino guinea pigs, and intradermal reactivity, and occular irritation test on albino rabbits were carried out with freeze-dried algal suspension in physiological salt solution. The sensitivity of guinea pigs is similar to that of humans. Microcystis, Anabaena, Cylindrospermopsis, and Aphanizomenon bloom and strain samples were examined in sensitization and irritation tests and no correlation was found between the toxin content and the allergenic character. The most toxic one (Microcystis aeruginosa) was not the most allergenic sample, but the nontoxic Aphanizomenon was the most allergenic one. The axenic strains were not allergenic at all. The pure microcystin LR was only slightly allergenic even in high concentration (1.5 mg/ml). Water and lipid soluble fractions were obtained by water and chloroform extraction of lyophilized algal suspensions. The chloroform fraction was bound on C18 cartridges and eluted by methanol in nine fractions. Only one of the lipid soluble fractions was skin irritative whereas the strongest irritative effect was shown by the water soluble fraction. PMID- 11769250 TI - Cytological alterations in isolated hepatocytes from common carp (Cyprinus carpio L.) exposed to microcystin-LR. AB - Microcystin-LR (MC-LR) is the most commonly encountered of the toxic cyclic peptide hepatotoxins occurring in China. It is a model compound for toxicological studies. In this study, the toxicity of MC-LR (50 and 500 micrograms/L) on isolated carp hepatocytes was determined and the ultrastructural alterations of cells induced by MC-LR were observed. The alterations noted when hepatocytes were exposed to 50 micrograms/L MC-LR were blebbing of cell membrane, shrinking and deformation of nuclei, vesiculation and transformation into concentric membrane whorls of RER, and swelling and rearrangement of the cytoskeleton. However, when the cells were exposed to 500 micrograms/L MC-LR, broken cell membranes, nuclei and cytoskeleton could be observed. These ultrastructural changes paralleled the pathological events, which lead to apoptosis or necrosis of hepatocytes. These results suggest that disruption of the cytoskeletal structures could account for the blebbing of cell membrane and apoptosis induced by MC-LR. PMID- 11769251 TI - Characterisation of a gene cluster involved in bacterial degradation of the cyanobacterial toxin microcystin LR. AB - A novel pathway for degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR was identified in a newly isolated Sphingomonas sp. (Bourne et al. 1996 Appl. Environ. Microbiol. 62: 4086-4094). We now report the cloning and molecular characterisation of four genes from this Sphingomonas sp. that exist on a 5.8-kb genomic fragment and encode the three hydrolytic enzymes involved in this pathway together with a putative oligopeptide transporter. The heterologously expressed degradation pathway proteins are enzymatically active. Microcystinase (MlrA), the first enzyme in the degradative pathway, is a 336 residue endopeptidase, which displays only low sequence identity with a hypothetical protein from Methanobacterium thermoautotrophicum. Inhibition of microcystinase by EDTA and 1,10-phenanthroline suggests that it is a metalloenzyme. The most likely residues that could potentially chelate an active site transition metal ion are in the sequence HXXHXE, which would be unique for a metalloproteinase. Situated immediately downstream of mlrA with the same direction of transcription is a gene mlrD, whose conceptual translation (MlrD, 442 residues) shows significant sequence identity and similar potential transmembrane spanning regions to the PTR2 family of oligopeptide transporters. A gene mlrB is situated downstream of the mlrA and mlrD genes, but transcribed in the opposite direction. The gene encodes the enzyme MlrB (402 residues) which cleaves linear microcystin LR to a tetrapeptide degradation product. This enzyme belongs to the "penicillin-binding enzyme" family of active site serine hydrolases. The final gene in the cluster mlrC, is located upstream of the mlrA gene and is transcribed in the opposite direction. It codes for MlrC (507 residues) which mediates further peptidolytic degradation of the tetrapeptide. This protein shows significant sequence identity to a hypothetical protein from Streptomyces coelicolor. It is suspected to be a metallopeptidase based on inhibition by metal chelators. It is postulated on the basis of comparison with other microorganisms that the genes in this cluster may all be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR. PMID- 11769252 TI - The effects of a cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors. AB - In an aquatic ecosystem, during cyanobacterial bloom lysis, a mixture of toxins and other cyanobacterial and bacterial components will be present in the water, acting on aquatic organisms. Most of the research into toxic effects of cyanobacteria has involved the use of purified toxins. In this study, the "real life" situation of a cyanobacterial lysis event was investigated. For this purpose, intact cells from a natural cyanobacterial bloom from Lake Muggelsee, Berlin, were taken and the cells were broken by repeated freeze/thaw cycles. This crude extract was used to expose several aquatic organisms ranging from microalgae (Scenedesmus armatus), macrophyte (Ceratophyllum demersum), invertebrate (Chaoborus crystallinus) up to fish eggs (Danio rerio) to look at several physiological parameters such as detoxication enzyme activity and, in the case of the microalgae and the macrophyte, also the effect on activity of photosynthesis. In all the tests, the cyanobacterial crude extract caused stronger effects than the pure cyanobacterial toxins used in equivalent concentrations. PMID- 11769253 TI - Population growth impairment of sulfur-containing compounds to Tetrahymena pyriformis. AB - A series of 37 aliphatic and aromatic sulfur-containing compounds were evaluated in 2-day Tetrahymena pyriformis population growth impairment assay. The results indicate that, except for select compounds, the in-ring sulfur-containing compounds, sulfates, sulfites, thiols, sulfones, and sulfoxides model as neutral and noncovalent-reacting narcotics. Abiotic loss due to volatility appears to interfere in accurate model prediction because actual toxicity was less than predicted. Vinyl sulfones and sulfoxides are more toxic than predicted using neutral narcosis. Tetrahymena exposed to methyl vinyl sulfone exhibits a direct relationship between the exposure concentration and the generation times with no lag phase in growth. As such, these population growth kinetics mimic those reported for hydrophilic neutral narcotics (i.e., ethanol and acetone). Tetrahymena exposed to phenyl vinyl sulfone exhibit a long concentration dependent lag phase, which is followed by population growth at rates not different from controls. These population growth kinetics are similar but more dramatic than those reported for hydrophobic neutral narcotics (i.e., butylbenzene and 2-decanone). These results are useful in that they imply that sulfur-containing compounds for the most part act as simple narcotics. Therefore, their toxicity can be modeled with simple structure-toxicity relationships without much fear of underestimation of potency. PMID- 11769254 TI - Concentrations of pesticide residues in tissues of fish from Kolleru Lake in India. AB - Kolleru Lake is the largest natural freshwater lake of Andhra Pradesh in India. It is situated between latitudes 16 degrees 32' and 16 degrees 47'N and longitudes 81 degrees 05' and 81 degrees 27'E. The use of pesticides for agricultural purposes is widespread in the Kolleru Lake region. The biological indicators like fish help in the studies of aquatic pollution by pesticides. Fish species Channa striata and Catla catla and water samples were collected from Kolleru Lake in each of three seasons over a period of three years. Fish samples were analyzed according to a modified method which is proposed for the gas chromatographic determination for the pesticides viz., alpha-BHC, gamma-BHC, malathion, chloirpyrifos, isodrin, endosulfan, dieldrin, and p,p-DDT. Water samples were analyzed for selected physico-chemical parameters. The extraction efficiency for the selected pesticides is between 82.8% and 91.2%. The maximum concentrations of pesticide residues in Kolleru Lake fish on wet weight basis are 123.8 micrograms/g for alpha-BHC, 98.7 micrograms/g for gamma-BHC, 2.5 micrograms/g for malathion, 88.6 micrograms/g for chlorpyrifos, 0.91 microgram/g for isodrin, 76.5 micrograms/g for endosulfan, 1.98 micrograms/g for dieldrin, and 157.4 micrograms/g for p,p'-DDT. These analyses were used to evaluate the baseline data and the pesticide pollution in the lake's ecosystem. PMID- 11769255 TI - The acute and chronic toxicity of cadmium and zinc to two hydra species. AB - The potential of two hydra species, Hydra vulgaris (pink) and Hydra viridissima (green), for use as invertebrate models for toxicity testing of waterborne metals was investigated. The acute and subchronic toxicities of cadmium (a nonessential metal) and zinc (an essential metal) were determined. Results showed that both the hydra species were more sensitive to cadmium than to zinc, and that green hydra were more sensitive than pink hydra. The mean (SE) 96 h LC50 values of cadmium and zinc for pink hydra were 83 (8.5) and 2300 (150) micrograms/L, respectively. For green hydra, the respective 96 h LC50 values for cadmium and zinc were 3.0 (0.0) and 935 (46.5) micrograms/L. The respective 7-day no-observed effect-concentrations (NOEC) and lowest-observed-effect-concentrations (LOEC) for pink hydra were < 13 and 13 micrograms/L for cadmium, and < 250 and 250 micrograms/L for zinc. The respective 7-day NOEC and LOEC values for green hydra were 0.4 and 0.8, microgram/L for cadmium, and 38 and 75 micrograms/L for zinc. Neither 1, 2, or 3 x 90-min pulse-exposures to 0.4, 0.8, or 1.5 micrograms/L of cadmium had any significant deleterious effect on total green hydra numbers after seven days in clean water. Green hydra appeared to be excellent freshwater invertebrate models for testing dissolved metals based on their sensitivity and the ability to rapidly assess population reproduction in the laboratory. PMID- 11769257 TI - [Agreements and disagreements in the Family Health Care Program team]. AB - OBJECTIVE: To identify issues that promote agreement and disagreement among doctors, nurses, and health care professionals who integrate the Family Health Care Program team. METHODS: A qualitative study using focus groups was carried out. The participants were male and female health care professionals, doctors and nurses from the Family Health Care Program team in Teresina, Brazil. Group sessions were conducted by a coordinator and with the participation of an observer and the following issues were raised: insertion in the program, capacitating process, main concepts of the program, relation with the organization and the prevailing health care model, relationships between the team members and the community, required and available services, work conditions and legal work situation, positive and negative factors. RESULTS: General issues such as community work, preventative care and teamwork brought out agreement among the three categories of professionals. Issues that reinforced the disagreement of the professional categories were salary levels, relationship with the community and team responsibility. CONCLUSIONS: Issues that brought out more disagreement were those that reinforced the corporate aspects of each professional category, while issues that promoted internal disagreement in each group were discussed based on external references, suggesting the need for better defining specific matters in the Family Health Care Program. Strategies to meet the community needs have proven to be a matter of urgency for the health care professionals since they are the first ones responsible for solving community health care services problems. PMID- 11769256 TI - Comparative sensitivity of embryo-larval toxicity assays with African catfish (Clarias gariepinus) and zebra fish (Danio rerio). AB - Embryo-larval toxicity tests with the African catfish (Clarias gariepinus) were conducted with five chemicals (Cr, Cd, Zn, NaPCP and malathion) and three environmental samples. The sensitivity of the 5-day assay was compared to that of the 12-day embryo-larval toxicity tests with the zebra fish (Danio rerio). The ratios of the C. gariepinus and D. rerio LC50 values ranged from 0.4 for Cr to 8.9 for Zn. The ratios of subchronic values ranged from 0.25 for NaPCP to 3.1 for Cd indicating a more comparable sensitivity of the two species. For the three sediment pore waters, the ratios were 0.6, 1.1, and 2.4 and the subchronic values were identical for the two species. The results suggest that, considering the short-test duration and its sensitivity, the 5-day embryo-larval tests with C. gariepinus may be a potential alternative for short-term embryo-larval toxicity testing with fish. PMID- 11769258 TI - [Effects of food deprivation levels on the oogenesis of Panstrongylus megistus]. AB - The effects of various levels of food deprivation on the oogenesis of P. megistus was studied. Immediately after the imaginal ecdysis, six groups (GI to GVI) of 15 couples each were formed. Each group was fed as follows: GI -- on days 5 and 25; G-II -- on days 5 and 35; GIII -- on days 5 and 45; GIV -- on day 20; GV -- on day 30; GVI -- on day 40 after the imaginal ecdysis. After the established fasting period, all groups were fed fortnightly. Fifteen couples were in the control group (CG), which was fed on the day 5 after the imaginal ecdysis and subsequently fortnightly. GI produced more eggs, matings and fertile eggs. GII had longer life spans, higher fecundity and hatchings. GIII had a shorter life span, low fecundity, fertility and hatchings. GVI presented the least favorable results for all parameters, except for the pre-oviposition period. The CG had the best results in all parameters when compared with all experimental groups. PMID- 11769259 TI - [Mycobacterium avium complex in water buffaloes slaughtered for consumption]. AB - Two mycobacterium strains isolated from lung tissue a apical lymph nodes of slaughtered water buffaloes were biochemically analyzed and identified as Mycobacterium avium complex strains. Association between these microorganisms and the acquired immunodeficiency syndrome, and the potential risk posed by eating infected animals and their products, was discussed. PMID- 11769260 TI - [Road accidents in a city in southern Brazil]. AB - The study was conducted in the municipality of Londrina, a medium-sized city of southern Brazil. Analysis was performed in the characteristics of road accidents that had occurred during the first semester of 1996, resulting in 3,643 victims. Car or small truck collisions were the most common type of accident. The rate of motorcycle-related injuries (per 1,000 registered vehicles) was seven times higher than that resulting from cars or small trucks. Fatality rates were higher for motorcyclists who collided with stationary objects (29.4%) and pedestrians who were injured by lorries or buses (22.2%), in comparison with a mean fatality rate of 1.8%. This information may provide a basis for the implementation of public policies aiming at reducing accidents. PMID- 11769261 TI - Cardiopulmonary resuscitation (CPR) during pregnancy. Working Group on CPR of the European Academy of Anaesthesiology. PMID- 11769262 TI - Aging with disabilities: must they go together? PMID- 11769263 TI - Litigation and neurodisability. PMID- 11769264 TI - Architecture of the medial gastrocnemius in children with spastic diplegia. AB - Ultrasound images were obtained of the medial gastrocnemius at different ankle joint positions with the knee extended. Fascicle length and deep fascicle angle were measured in five normally developing adults (mean age 33 years, age range 24 to 36 years) and in five normally developing children (mean age 7.8 years, age range 7 to 11 years), and in seven children with spastic diplegia (mean age 10 years, age range 6 to 13 years). These architectural variables were similar in the groups of normally developing adults and children. Importantly, no statistical difference could be found between the normally developing children and those with diplegia for fascicle length. Deep fascicle angles were reduced significantly in the clinical group at a particular ankle joint angle but not at the resting angles. The difference in deep fascicle angles is explained as a function of resting muscle length and is not attributed any clinical importance. Our results do not explain the structural origin of muscle contracture explicitly. However, they do indicate that most of the fixed shortness in the medial gastrocnemii of ambulant children with spastic diplegia is not due to reduced muscle fascicle length. We suggest that muscle contracture may be better explained in terms of shortness of the aponeuroses of pennate muscles, such as the medial gastrocnemius, through reduced muscle fascicle diameter. PMID- 11769265 TI - Treatment of knee contracture in cerebral palsy by hamstring lengthening, posterior capsulotomy, and quadriceps mechanism shortening. AB - Results of surgery to correct fixed flexion contracture of the knee and improve voluntary knee extension in 39 knees in 20 children (11 females, 9 males; mean age 12 years 8 months, age range 5 to 20 years) with cerebral palsy were analyzed. All patients had neuromotor disease and 18 children had spastic diplegia or quadriplegia. All patients could initiate voluntary knee extension but lacked full passive extension. Five patients (10 knees) were free walkers with a mean motor severity index of 19 and mean fixed knee contracture of 20 degrees. Fifteen patients (29 knees) were not free walkers and 13 were wheelchair ambulators. They had a mean motor severity index of 8 and mean fixed knee contractures of 30 degrees. Surgical procedures included various combinations of hamstring lengthening and/or posterior capsulotomy to allow free passive knee extension, with or without quadriceps mechanism shortening, to enhance voluntary extension. The best results were in patients who had hamstring lengthening, posterior capsulotomy, and quadriceps mechanism shortening. PMID- 11769266 TI - Hip pain in 234 non-ambulatory adolescents and young adults with cerebral palsy: a cross-sectional multicentre study. AB - In orthopaedic clinical practice hip pain is the main complaint of adults with cerebral palsy (CP). The aim of this descriptive study was to specify prevalence of hip pain and to propose methods of care other than surgery. The study was a cross sectional multicentre one based in the Rhjne-Alpes region. Patients over 15 years of age, with CP who were non-ambulatory were included. Two hundred and thirty-four patients were questioned. Mean age of the patients was 27 years 10 months, median 26 years 1 month, with 59.3% males and 40.7% females. Patients were questioned about pain with precise information about the circumstances of pain, tolerance, and treatment. Pain was judged to be intolerable if it prevented usual activities. Prevalence of hip pain was 47.2%. Pain was judged to be tolerable in 35.6% of the 234 patients, i.e. in 75.5% of patients with hip pain. There were three types of pain: provoked pain, pain linked to position, and spontaneous pain. Medical treatment was given to only 13.6% of patients with hip pain. The first treatment for hip pain is to avoid circumstances where pain occurs; medical treatment is reserved for when daily life cannot be adapted sufficiently to prevent pain. Medical treatment must be appropriate with doses of adequate strength before proposing surgery. PMID- 11769267 TI - Parent and teacher report of pragmatic aspects of communication: use of the children's communication checklist in a clinical setting. AB - The Children's Communication Checklist (CCC) was developed to provide an objective assessment of pragmatic aspects of children's communication difficulties. We aimed to (1) see whether the checklist provided valid and reliable information when completed by parents, and (2) consider its usefulness in a clinical context. Checklists were completed by parents and a professional who knew the child well for all 5 to 17-year-old referrals to a tertiary developmental paediatrics centre over a 31-month period. Children who were not yet speaking in sentences were excluded. From a sample of 151 children (81% male; mean age 8.7 years) with pervasive or specific developmental disorders, valid checklists were completed by 119 parents and 93 professionals. Reliability, as measured by internal consistency, was 0.7 or higher for most scales. Correlations between ratings for parents and professionals were in the range of 0.30 to 0.58 for individual pragmatic scales, with a correlation of 0.46 (n=82) for the pragmatic composite. For both parents and professionals, the pragmatic composite was lowest for children with a diagnosis of autism; intermediate for those with a diagnosis of Asperger syndrome, pervasive developmental disorder not otherwise specified or attention-deficit-hyperactivity disorder (ADHD); and highest for those with a diagnosis of specific learning disability. The strongest relation between the pragmatic composite and diagnosis was seen when ratings from parents and professionals were combined. Differences between diagnostic groups were not explicable in terms of age or verbal IQ. PMID- 11769268 TI - Chronic posttraumatic headache in children and adolescents. AB - Little is known about chronic posttraumatic headache (PTH) in children and adolescents. In this study we report on symptoms, clinical findings, and management of all children seen in our headache clinic who presented with recurrent headache following head injuries. A total of 23 children were identified over a period of 4 years. Twenty-one children (13 male, eight female; mean age 11.2 years, age range 3.3 to 14.9 years, median 12.1 years) fulfilled the International Headache Society's clinical criteria for the diagnosis of chronic PTH. Mean duration of headache was 13.3 months (range 2 to 60 months, median 7 months). Children were followed up for a period of 5 to 29 months (mean 12.5 months, median 9 months). Head injuries were classified as serious in four patients and minor in 17. Clinical variables were compared between children with PTH and those without a history of head injury. The headaches were migraine in five patients, tension type in 13, and mixed in three patients. Tension-type headache was significantly more common in children with chronic PTH than in those with no history of head injury, but the clinical course was comparable in the two groups. PMID- 11769269 TI - Abilities and attainment in Smith-Magenis syndrome. AB - This study reports on cognitive abilities and attainment in 29 children and 21 adults with Smith-Magenis syndrome. There were 13 boys and 16 girls aged 6 to 16 years, and nine men and 12 women aged 16 to 52 years. All had mild to severe learning disabilities* with no differences overall between verbal and performance skills, but with a particular profile of cognitive strengths and weaknesses. Levels of attainment and of adaptive behaviour were strikingly low, and the group of adults emerged as much more dependent on carers than might have been expected from their general level of intellectual functioning. Reasons for this discrepancy are explored in terms of the severe behavioural difficulties characteristic of the syndrome. PMID- 11769270 TI - Management of constipation in children with disabilities. PMID- 11769271 TI - Vigabatrin. PMID- 11769272 TI - General movement assessment as a method of developmental neurology: new paradigms and their consequences. The 1999 Ronnie MacKeith lecture. PMID- 11769273 TI - Deletion of 8p: a report of a child with normal intelligence. AB - The case is presented of a female infant with a distal deletion of 8p (8p23.1- >pter) whose development was monitored over a 5-year period from 12 months of age. Although previous literature has suggested that 8p deletion is associated with mild to moderate intellectual disability, the child reported here has normal intelligence. Despite initial delays in gross motor and language skills, cognitive development (assessed with the Bayley Scales of Infant Development) and intellectual ability (measured on the Stanford-Binet Intelligence Scale) were within average range. It is argued that the small number of previous case reports may have created a misleading impression of intellectual development in individuals with distal deletions of 8p. PMID- 11769274 TI - 'Foetal valproate syndrome and autism: additional evidence of an association'. PMID- 11769275 TI - 'Ketogenic diet and surgery'. PMID- 11769276 TI - Genomic structure of the human DNA mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC). PMID- 11769277 TI - Fasciola hepatica and lymnaeid snails occurring at very high altitude in South America. AB - Fascioliasis due to the digenean species Fasciola hepatica has recently proved to be an important public health problem, with human cases reported in countries of the five continents, including severe symptoms and pathology, with singular epidemiological characteristics, and presenting human endemic areas ranging from hypo- to hyperendemic. One of the singular epidemiological characteristics of human fascioliasis is the link of the hyperendemic areas to very high altitude regions, at least in South America. The Northern Bolivian Altiplano, located at very high altitude (3800-4100 m), presents the highest prevalences and intensities of human fascioliasis known. Sequences of the internal transcribed spacers ITS-1 and ITS-2 of the nuclear ribosomal DNA of Altiplanic Fasciola hepatica and the intermediate snail host Lymnaea truncatula suggest that both were recently introduced from Europe. Studies were undertaken to understand how the liver fluke and its lymnaeid snail host adapted to the extreme environmental conditions of the high altitude and succeeded in giving rise to high infection rates. In experimental infections of Altiplanic lymnaeids carried out with liver fluke isolates from Altiplanic sheep and cattle, the following aspects were studied: miracidium development inside the egg, infectivity of miracidia, prepatent period, shedding period, chronobiology of cercarial emergence, number of cercariae shed by individual snails, survival of molluscs at the beginning of the shedding process, survival of infected snails after the end of the shedding period and longevity of shedding and non-shedding snails. When comparing the development characteristics of European F. hepatica and L. truncatula, a longer cercarial shedding period and a higher cercarial production were observed, both aspects related to a greater survival capacity of the infected lymnaeid snails from the Altiplano. These differences would appear to favour transmission and may be interpreted as strategies associated with adaptation to high altitude conditions. PMID- 11769278 TI - Multiple strategies of schistosomes to meet their requirements in the intermediate snail host. AB - The results of the studies on our model combination Trichobilharzia ocellata Lymnaea stagnalis, presented in this review, lead to the conclusion that schistosomes use multiple strategies to reach their goals, i.e. to propagate and to continue their life cycle. They have to escape from being attacked by the internal defence system (IDS) of the snail host and to profoundly affect the host's energy flow, of which reproduction and growth are the main determinants, for their own benefit. These physiological changes they establish mainly by interfering with the two regulatory systems in the snail host, the IDS and the neuroendocrine system (NES). Moreover, these two regulatory systems clearly interact with each other. Parasitic E/S products affect the host's IDS both in a direct and an indirect way. The neuropeptides or neuropeptide-like substances that are secreted by parasite glands into the host directly suppress haemocyte activity in the snail. The indirect effects include effects of (1) peptides from connective tissue cells and (2) neuropeptides from NES and/or IDS. Parasitic E/S products also induce the effects on energy flow in the host. These E/S products act either directly on a target, as shown for the inhibiting effect of the parasite on the development of the male copulation organ, or on the NES regulating reproductive activity, e.g. on gene expression. Indirect effects of E/S products on the NES (hormone-receptor interaction, electrical activity) are mediated by a factor from connective tissue cells, presumably belonging to the IDS. The physiological changes in the snail host are obviously of vital importance for the parasites, since they make use of different strategies to bring them about. PMID- 11769279 TI - Receptor-ligand interactions and cellular signalling at the host-parasite interface. AB - Although the effects of trematode infection on snail host physiology or host responses on parasite development have been well described in the literature, very little is known regarding the underlying mechanisms and specific molecules responsible for mediating those effects. It is presumed that many host-parasite interactions are communicated through receptor-mediated events, in particular those involving haemocytic immune responses to invading parasites, larval motility and migration through host tissues, and larval acquisition of host molecules either as nutrients or critical developmental factors. The intent of this chapter is to review current knowledge of molecules (both receptors and their ligands or counter-receptors) involved in molecular communication at the interface between larval trematodes, especially the mother or primary sporocyst stage, and host cells/tissues in intimate proximity to developing larvae. Information to date suggests that the molecular exchange at this interface is a highly complex and dynamic process, and appears to be regulated in specific cases. Topics discussed will focus on snail cell receptor interactions with the sporocyst tegument and its secretions, host cell-cell and cell-substrate adhesion receptors and their related signal transduction pathways, and sporocyst tegumental surface receptors and ligands involved in the binding of soluble host molecules. PMID- 11769280 TI - Mechanisms of molluscan host resistance and of parasite strategies for survival. AB - In parallel with massive research efforts in human schistosomiasis over the past 30 years, persistent efforts have been made to understand the basis for compatibility and incompatibility in molluscan schistosomiasis. Snail plasma contains molecules that are toxic to trematodes, but these seem to kill only species that never parasitize the mollusc used as the source of plasma. A sporocyst will be killed actively by haemocytes alone if they are from a snail that is resistant to the trematode. Oxygen-dependent killing mechanisms play a major role. Enzymes such as NADPH oxidase, superoxide dismutase, myeloperoxidase and nitric oxide synthase are critical components of the putative killing pathways. Metabolic intermediates such as hydrogen peroxide and nitric oxide appear to be more important against trematodes than the shorter-lived intermediates that are more important in anti-microbial defences. Products secreted by trematode larvae influence the physiology of snail haemocytes, implying active counter-defences mounted by the parasite, but these remain largely unexplored. A possible molecular basis for the susceptibility/resistance dichotomy in molluscan schistosomiasis is suggested to be deficient forms of enzymes in the respiratory burst pathway, and a selective disadvantage for schistosome resistance is an integral component of this model. PMID- 11769281 TI - The relationship between Schistosoma mansoni and Biomphalaria glabrata: genetic and molecular approaches. AB - Biomphalaria glabrata is a major intermediate host for the helminth parasite Schistosoma mansoni. Beginning in the mid-20th century, studies were carried out with this snail species to identify the immunological and genetic components that might be involved in controlling schistosome development. A number of genetically well-defined snail stocks were derived as a direct result of these studies and have since played major roles in helping investigators to identify important cellular and humoral components in the snail/schistosome relationship. This review will explore the historical development of these stocks and describe some of the major advances in several areas of medical malacology that hawe been made possible be their use. PMID- 11769282 TI - Molecular approaches in the study of Biomphalaria glabrata--Schistosoma mansoni interactions: linkage analysis and gene expression profiling. AB - Gene mapping and the generation of linkage groups are fundamental to an understanding of the organization and relationships of genes and marker sequences, providing a framework with which to investigate their association with traits of interest. The abundance of techniques available for generating polymorphic molecular markers, and recent advances in high throughput screening, have allowed the extension of map analysis to the tropical freshwater snail Biomphalaria glabrata, an important intermediate host for Schistosoma mansoni. Direct comparison of gene expression by differential display screening, without prior identification of candidate genes, can be combined with mapping to quantify the involvement of specific sequences in the schistosome resistance response, and other important host-parasite interactions. Here we discuss the application of current and emergent technologies to gene characterization and linkage analysis in snail-schistosome interactions. Preliminary results from the analysis of comparative gene expression in resistant and susceptible snails are also presented. PMID- 11769283 TI - Trematode infection and the distribution and dynamics of parthenogenetic snail populations. AB - According to the Red Queen hypothesis for sex, cross-fertilization should be positively associated with the probability of exposure (risk) to virulent parasites. Unfortunately, risk is difficult to measure in the wild, and prevalence of infection is often substituted for risk. Here I suggest that prevalence of infection may not generally suffice as a surrogate for risk, since the Red Queen model can make opposite predictions depending on the distribution of risk in the wild. Specifically, the results of a matching-alleles model suggest that asexual populations should be more infected than sexual populations, when (1) the variance in risk among populations is small, and (2) the mean risk of exposure to parasites is near the point where selection switches to favouring sex over asex. If, however, the variance in risk among populations is large, sexual reproduction should be positively associated with the prevalence of infection. In addition, the coefficient of variation for reproductive mode should increase sharply at the switch point. In light of these results, I re-evaluated data from two studies on the distribution of males in 95 populations of a freshwater snail (Potamopyrgus antipodarum). Populations of these snails are often mixtures of sexual and asexual individuals, and the frequency of males is correlated with the frequency of sexual females in the population. The results show a large, highly skewed variance among populations for prevalence of infection by larval trematodes. The results also show a positive, significant relationship between prevalence of infection and the frequency of males, with a sharp increase in the coefficient of variation at intermediate prevalence. In addition, experimental studies suggest that some of the necessary conditions of the Red Queen hypothesis are also met in this system. Specifically, the most common trematode infecting these snails is (1) adapted to infecting local host populations of the snail, and is (2) more infective to clones that were common in the recent past. It is too early to knoxv if the parasite theory is sufficient to explain the widespread distribution of sex. I suggest that the theory is not sufficient, but that parasites in combination with mutation accumulation in clonal lines may explain the maintenance of sex in species that occasionally produce apomictic mutants. PMID- 11769284 TI - Genetic variability and molecular identification of Brazilian Biomphalaria species (Mollusca: Planorbidae). AB - Freshwater snails belonging to the genus Biomphalaria are intermediate hosts of the trematode Schistosoma mansoni in the Neotropical region and Africa. In Brazil, one subspecies and ten species of Biomphalaria have been identified: B. glabrata, B. tenagophila, B. straminea, B. occidentalis, B. peregrina, B. kuhniana, B. schrammi, B. amazonica, B. oligoza, B. intermedia and B.t. guaibensis. However, only the first three species are found naturally infected with S. mansoni. The classical identification of these planorbids is based on comparison of morphological characteristics of the shell and male and female reproductive organs, which is greatly complicated by the extensive intra-specific variation. Several molecular techniques have been used in studies on the identification, genetic structure as well as phylogenetic relationships between these groups of organisms. Using the randomly amplified polymorphic DNAs (RAPD) analysis we demonstrated that B. glabrata exhibits a remarkable degree of intra specific polymorphism. Thus, the genetics of the snail host may be more important to the epidemiology of schistosomiasis than those of the parasite itself. Using the simple sequence repeat anchored polymerase chain reaction (SSR-PCR) in intra populational and intra-specific studies we have demonstrated that snails belonging to the B. straminea complex (B. straminea, B. kuhniana and B. intermedia) clearly presented higher heterogeneity. Using the low stringency polymerase chain reaction (LS-PCR) technique we were able to separate B. glabrata from B. tenagophila and B. tenagophila from B. occidentalis. To separate all Brazilian Biomphalaria species we used the restriction fragment length polymorphism (PCR-RFLP) of the internal transcribed spacer region (ITS) of the DNA gene. The method also proved to be efficient for the specific identification of DNA extracted from snail eggs. Recently we have sequenced the ITS2 region for phylogenetic studies of all Biomphalaria snails from Brazil. PMID- 11769285 TI - Schistosoma mansoni and Biomphalaria: past history and future trends. AB - Schistosoma mansoni is one of the most abundant infectious agents of humankind. Its widespread distribution is permitted by the broad geographic range of susceptible species of the freshwater snail genus Biomphalaria that serve as obligatory hosts for its larval stages. Molecular phylogenetic studies suggest that Schistosoma originated in Asia, and that a pulmonate-transmitted progenitor colonized Africa and gave rise to both terminal-spined and lateral-spined egg species groups, the latter containing S. mansoni. Schistosoma mansoni likely appeared only after the trans-Atlantic dispersal of Biomphalaria from the Neotropics to Africa, an event that, based on the present African fossil record, occurred only 2-5 million years ago. This parasite became abundant in tropical Africa and then entered the New World with the slave trade. It prospered in the Neotropics because a remarkably susceptible and productive host, B. glabrata, was widely distributed there. Indeed, a snail similar to B. glabrata may have given rise to the African species of Biomphalaria. Schistosoma mansoni has since spread into other Neotropical Biomphalaria species and mammalian hosts. The distribution of S. mansoni is in a state of flux. In Egypt, S. mansoni has nearly completely replaced S. haematobium in the Nile Delta, and has spread to other regions of the country. A susceptible host snail, B. straminea, has been introduced into Asia and there is evidence of S. mansoni transmission in Nepal. Dam and barrage construction has lead to an epidemic of S. mansoni in Senegal, and the parasite continues its spread in Brazil. Because of competition with introduced aquatic species and environmental changes, B. glabrata and consequently S. mansoni have become less abundant on the Caribbean islands. Control of S. mansoni using praziquantel and oxamniquine has reduced global prevalence but control is difficult to sustain, and S. mansoni can develop tolerance/resistance to praziquantel, raising concerns about its future efficacy. Because of legitimate environmental concerns, snail control is unlikely to be an option in future control efforts. Global warming will impact the distribution of Biomphalaria and S. mansoni, but the magnitude and nature of the effects are poorly understood. PMID- 11769286 TI - Evolutionary relationships between trematodes and snails emphasizing schistosomes and paragonimids. AB - Snails and digeneans have been associated for at least 200 million years. Their inter-relationships over such a time-span must have been complex and varied. Few studies have attempted to explore these relationships in the light of knowledge of the phylogeny of both host and parasite groups. Here we focus on two important families of digeneans, the Schistosomatidae and the Paragonimidae, for which molecular phylogenies are available. We investigate the types of evolutionary relationships between host and parasite, operating at different phylogenetic depths, that might explain current host specificity and distributions of both associates. Both families of parasites utilise a number of highly diverged gastropod families, indicating that host extensions have featured in their histories. However, schistosomatids and paragonimids show different patterns of association with their snail hosts. As befits the apparently more ancient group, schistosomatids utilise snails from across a wide phylogenetic range within the Gastropoda. The genus Schistosoma itself has experienced one long-range host switch between pulmonates and caenogastropods. By contrast, paragonimids are restricted to two superfamilies of caenogastropods. Despite these differences, modern schistosomatid species appear to be more host specific than are paragonimids and host additions, at the level of host family, are far less common among species of schistosomatids than among paragonimids. Some species of Paragonimus exhibit remarkably low levels of host specificity, with different populations utilising snails of different families. Existing knowledge relating to the phenomenon will be presented in the context of phylogenies of schistosomatids, paragonimids, and their snail hosts. Discussion focuses on the usefulness of current theories of snail-digenean coevolution for interpreting these findings. In the past, much emphasis has been placed on the idea that digeneans engage in a one-to-one arms race with their snail host. We consider that phylogenetic tracking rather than an arms-race relationship might be a common alternative. Not being bound by the restrictions imposed by an arms race, some digeneans might be able to extend to new host species more easily than the literature suggests. Switches into related host taxa are most likely. However, ecologically equivalent but unrelated gastropod hosts may also be exploited. Given the right ecological setting, digeneans are able to switch across considerable phylogenetic distances. Examples from the Paragonimidae and Schistosomatidae are given. PMID- 11769287 TI - Interactions between intermediate snail hosts of the genus Bulinus and schistosomes of the Schistosoma haematobium group. AB - Within each of the four species groups of Bulinus there are species that act as intermediate hosts for one or more of the seven species of schistosomes in the Schistosoma haematobium group, which includes the important human pathogens S. haematobium and S. intercalatum. Bulinus species have an extensive distribution throughout much of Africa and some surrounding islands including Madagascar, parts of the Middle East and the Mediterranean region. Considerable variation in intermediate host specificity can be found and differences in compatibility between snail and parasite can be observed over small geographical areas. Molecular studies for detection of genetic variation and the discrimination of Bulinus species are reviewed and two novel assays, allele-specific amplification (ASA) and SNaPshot, are introduced and shown to be of value for detecting nucleotide changes in characterized genes such as cytochrome oxidase 1. The value and complexity of compatibility studies is illustrated by case studies of S. haematobium transmission. In Senegal, where B. globosus, B. umbilicatus, B. truncatus and B. senegalensis may act as intermediate hosts, distinct differences have been observed in the infectivity of different isolates of S. haematobium. In Zanzibar, molecular characterization studies to discriminate between B. globosus and B. nasutus have been essential to elucidate the roles of snails in transmission. B. globosus is an intermediate host on Unguja and Pemba. Further studies are required to establish the intermediate hosts in the coastal areas of East Africa. Biological factors central to the transmission of schistosomes, including cercarial emergence rhythms and interactions with other parasites and abiotic factors including temperature, rainfall, water velocity, desiccation and salinity are shown to impact on the intermediate host-parasite relationship. PMID- 11769288 TI - Bulinus species on Madagascar: molecular evolution, genetic markers and compatibility with Schistosoma haematobium. AB - Of the four species of Bulinus found on Madagascar, three species: B. obtusispira, B. liratus and B. bavayi are endemic while the fourth, B. forskalii, is probably a recent introduction from the African mainland. The evolutionary relationships of these species with Bulinus species from Africa were studied by phylogenetic analysis of DNA sequence variation at two mitochondrial loci: cytochrome oxidase subunit I (COI) and large ribosomal subunit (LSU) or 16S. The observed levels of nucleotide divergence within Bulinus were substantial but may underestimate the true levels as there was evidence of 'saturation' of transitional substitutions at both loci. A putative secondary structure model for the sequenced segment of the 16S was developed. Subsequent phylogenetic analysis using transversional changes only for both loci, showed that there were contrasting levels of divergence within the four species groups. B. obtusispira was consistently placed within the B. africanus group, appearing ancestral to this group and was closest to the basal node within Bulinus. Together with B. bavayi, the two species appear to have been isolated on Madagascar for a long time, contrasting with both B. liratus and B. forskalii that appear more recent colonisers; however, estimate of exact times of divergence is problematic. A PCR RFLP assay was developed to enable identification and discrimination of B. obtusispira and B. liratus using discriminatory variation within the COI. To enable population genetic analysis within B. obtusispira, microsatellite markers were developed using an enrichment method and 8 primer pairs are reported. Laboratory infection experiments using Madasgacan S. haematobium from the Mahabo area showed that certain populations of B. obtusispira, B. liratus and B. bavayi were compatible. PMID- 11769289 TI - Genetic structure in natural populations of flukes and snails: a practical approach and review. AB - Several aspects of the coevolutionary dynamics in host-parasite systems may be better quantified based on analyses of population structure using neutral genetic markers. This includes, for example, the migration rates of hosts and parasites. In this respect, the current situation, especially in fluke-snail systems is unsatisfactory, since basic population genetics data are lacking and the appropriate methodology has rarely been used. After reviewing the forces acting on population structure (e.g. genetic drift or the mating system) and how they can be analysed in models of structured populations, we propose a simplified, indicative framework for conducting analyses of population structure in hosts and parasites. This includes consideration of markers, sampling, data analysis, comparison of structure in hosts and parasites and use of external data (e.g. from population dynamics). We then focus on flukes and snails, highlighting important biological traits with regard to population structure. The few available studies indicate that asexual amplification of flukes within snails strongly influences adult flukes populations. They also show that the genetic structure among populations in strongly affected by traits in other than snails (e.g. definitive host dispersal behaviour), as snails populations have limited migration. Finally more studies would allow us to deepen our current understanding of selective interference between flukes and snails (e.g. manipulation of host mating system by parasites), and evaluate how this affect population structure at neutral markers. PMID- 11769290 TI - Molecular evolution of freshwater snail intermediate hosts within the Bulinus forskalii group. AB - Freshwater snails of the Bulinus forskalii group are one of four Bulinus species complexes responsible for the transmission of schistosomes in Africa and adjacent regions. The species status of these conchologically variable and widely distributed planorbids remains unclear, and parasite compatibility varies considerably amongst the eleven taxa defined, making unambiguous identification and differentiation important prerequisites for determining their distributions and evolutionary relationships. Random Amplified Polymorphic DNA (RAPD) analyses were used to investigate relationships between taxa, with particular emphasis on Central and West African representatives. RAPD-derived phylogenies were compared with those from other independent molecular markers, including partial sequences of mitochondrial cytochrome oxidase subunit I (COI) gene, and the nuclear ribosomal RNA internal transcribed spacer 1 region (ITS1). The phylogenetic reconstructions from the three approaches were essentially congruent, in that all methods of analysis gave unstable tree topologies or largely unresolved branches. There were large sequence divergence estimates between species, with few characters useful for determining relationships between species and limited within species differentiation. Nuclear and mtDNA sequence data from Central and East African representatives of the pan-African B. forskalii showed little evidence of geographical structuring. Despite the unresolved structure within the phylogenies, specimens from the same species clustered together indicating that all methods were capable of differentiating taxa but could not establish the inter-specific relationships with confidence. The limited genetic variation displayed by B. forskalii, and the evolution and speciose nature of the group, are discussed in the context of the increasingly arid climate of the late Miocene and early Pliocene of Africa. PMID- 11769291 TI - Snail-trematode life history interactions: past trends and future directions. AB - Life history traits expressed by organisms vary due to ecological and evolutionary constraints imposed by their current environmental conditions and genetic heritage. Trematodes often alter the life history of their host snails by inducing parasitic castration. Our understanding of the variables that influence the resulting changes in host growth, fecundity and survivorship is insufficient to confidently predict specific outcomes of novel snail-trematode combinations. In a literature review of the last 30 years, we found 41 publications examining various life history characteristics of trematode-infected snails. These publications reported 113 different field and laboratory experiments involving 30 snail species and 39 trematode species and provided a data set for assessing factors that potentially affect life history outcomes. Analysis of the diverse responses across various snail-trematode systems and experimental conditions teased out general patterns for the expression of host growth, fecundity and survival. These were used to address existing hypotheses and develop several new ones relating the response of snail-trematode interactions to environmental and genetic factors. Finally, we propose directions for future experiments that will better assess the ecological and evolutionary factors influencing snail life history responses to trematode parasitism. PMID- 11769292 TI - Coevolution and compatibility in the snail-schistosome system. AB - In stark contrast to the huge body of theoretical work on the importance of hosts and parasites as selective agents acting on each other, until recently, little systematic empirical investigation of this issue has been attempted. Research on snail-schistosome interactions have, therefore, the potential for making an important contribution to the study of coevolution or reciprocal adaptation. This may be particularly pertinent since snail-schistosomes represent an indirectly transmitted macroparasite system, so often overlooked amongst both theoretical and empirical studies. Here we review ideas and experiments on snail-schistosome interactions, with particular emphasis on those that may have relevance to the potential coevolution between host resistance and parasite infectivity and virulence. We commence with an introduction and definition of the general concepts, before going into detail of some specific studies to illustrate these: evidence of snail-schistosome coevolutionary process in the field; evidence of coevolutionary processes in the laboratory; a general assessment of the applicability of coevolutionary models in snail-schistosome interactions; and finishing with a section on conclusions and areas for further study. PMID- 11769293 TI - A perspective on the ecology of trematode communities in snails. AB - This paper presents a perspective on the ecology of trematodes in snail hosts based on recent evidence. Because flukes use snails almost obligatorily as first intermediate hosts, we highlight the role of gastropods as keystone species for trematodes and their communities. After reviewing recent developments in the transmission of trematodes to and from snails, we discuss trematode communities within individual snails (infracommunities) and in snail populations (component communities). Results garnered using various protocols at the infracommunity level are reviewed. The few data available, all from marine systems, indicate that low colonization rates characterize infracommunities, suggesting that trematode infracommunities tend to be isolationist in character rather than interactive. The variety of trematode species present in a component community seems to be determined by spatial overlap of definitive hosts. Relative abundance of species in a component community shows little dependence on negative interspecific interactions at the level of the infracommunity. Temporal aspects of trematode communities are related to the life history of the host snail. The component communities of long-lived snails (mostly marine) integrate many infection episodes whereas shorter-lived snails (mostly freshwater) acquire new component communities each time host cohorts turnover. PMID- 11769294 TI - Seasonality in the transmission of schistosomiasis and in populations of its snail intermediate hosts in and around a sugar irrigation scheme at Richard Toll, Senegal. AB - Irrigation for intensive sugar cultivation started in the early 1980s at Richard Toll, some 100 km from the mouth of the Senegal River. Infections with Schistosoma mansoni were first seen in late 1988. This study records quantitative snail surveys for over 3 years from 1992 at sites representing different habitats in and around the irrigation scheme. Populations of both Biomphalaria pfeifferi (the intermediate host of S. mansoni) and Bulinus spp. (mainly B. truncatus, the local host of S. boris) peaked in late 'spring' or early 'summer', depending on the habitat, and then remained low until the following spring', B. pfeifferi favoured smaller, man-made habitats with most transmission between May and August each year. The less abundant Bulinus spp. favoured larger natural and man-made habitats with most S. bovis transmission between April and July. S. mansoni infections were more, but S. bovis infections were less abundant than other trematodes in their respective snail hosts. Ecological changes in the early 1980s due to sugar irrigation pre-dated similar, more widespread changes in the late 1980s when the completion of dams across the Senegal River prevented seasonal rain fed floods and sea water intrusion. S. mansoni has since spread rapidly around Richard Toll. The incompatibility of the local S. haematobium strains with the dominant bulinid snails has so far prevented an epidemic of urinary schistosomiasis at Richard Toll, but the invasion of similar downstream habitats by susceptible B. globosus is worrying. The principal control measure, chemotherapy, given in the 'winter' would minimise the rate of reinfection. It could be reinforced by judicious mollusciciding within the sugar irrigation scheme but not elsewhere. PMID- 11769295 TI - Contributions to and review of dicrocoeliosis, with special reference to the intermediate hosts of Dicrocoelium dendriticum. AB - An epidemiological study on dicrocoeliosis caused by Dicrocoelium dendriticum was carried out on sheep, molluscs and ants in the mountains of Leon province (NW Spain) between 1987-1991. The results concerning the intermediate hosts and a review of some aspects of dicrocoeliosis are summarized. Mollusc collection for the helminthological study was random throughout the study area at fortnightly intervals. Twenty-nine Gastropoda species were identified. D. dendriticum infection was only detected in 2.98%, of the 2084 Helicella itala examined and in 1.06% of 852 H. corderoi. The highest infection prevalence was detected in H. itala in September and in H. corderoi in February. Daughter sporocysts with well developed cercariae predominated in spring and autumn. Infection prevalence increased with mollusc age and size. Ants were collected from anthills or plants to which they were attached. The behaviour of ants in tetania was followed. Twenty-one Formicidae species were identified, but only the following harboured D. dendriticum: Formica cunicularia (1158 examined specimens, 0.69% infection prevalence, 2-56 metacercariae per ant); F. sanguinea (234, 1.28%, 2-63); F. nigricans (1770, 4.97%, 1-186); F. rufibarbis (288, 6.59%, 2-107). In a flat area close to Leon town, 95.39% of the 2085 F. rufibarbis specimens collected in tetania contained metacercariae (1-240) in the abdomen. These were used for parasite characterization by isoelectric focusing and to infect lambs and hamsters. Only one brainworm per ant was found. PMID- 11769296 TI - A CQI intervention to change the care of depression: a controlled study. AB - CONTEXT: Although new strategies for managing depression in primary care (e.g., nurse telephone calls, collaborative care) have been shown to be effective, no models are available for their systematic implementation in the "real world." OBJECTIVE: To test whether a continuous quality improvement (CQI) intervention could be used to implement systems in primary care clinics to improve the care and outcomes for patients diagnosed with depression. DESIGN: Before-after study with concurrent controls. INTERVENTION: A multidisciplinary team from the three intervention clinics developed and implemented a graded set of five care management options, ranging from watchful waiting (nurse telephone call in 4 to 6 weeks) to mental health management, which clinicians could order for their patients with depression. SETTING: 9 primary care clinics in greater Minneapolis St. Paul, Minnesota. PATIENTS: Outpatients 18 years of age and older whose primary care clinic visit included an International Classification of Diseases, 9th revision, code for depression and who completed baseline and 3-month follow up surveys before and after the intervention. MAIN OUTCOME MEASURES: Measures of process of care (follow-up depression visits to physician, mental health visits, follow-up telephone calls) and outcomes of care (improved depression symptoms over 3 months, satisfaction with care). RESULTS: Although the CQI team appeared to function well, only 30 of the 257 patients identified from depression-coded visits for this study were referred to the new system during the 3-month evaluation period. In both the intervention and control clinics, follow-up visits, mental health referrals, and follow-up telephone calls did not improve significantly from the preintervention levels of about 0.5 for a primary care visit, 0.4 for a mental health visit, or 0.1 for a follow-up phone call per person. The same was true of patient outcomes: The proportion of patients in the intervention and control clinics who had improved depression symptoms and those who were very satisfied with their depression care did not change significantly from the preintervention levels of 43% and 26%, respectively. CONCLUSIONS: Our attempt to improve the primary care management of depression failed because physicians used the new order system so infrequently. Whether a greater leadership commitment to change or a different improvement process would alter our findings is an open question. PMID- 11769297 TI - Caregiver perceptions of the reasons for delayed hospital discharge. AB - CONTEXT: Financial pressures have increased the emphasis on expeditious hospital discharge. Identification of barriers to timely discharge may help direct efforts to decrease unnecessary hospital days. OBJECTIVE: To identify caregivers' perceptions of reasons for discharge delays at an academic medical center. DESIGN: Survey and free-form written responses using a convenience sample (overall response rate, 68%). RESPONDENTS: 104 housestaff, 34 attending physicians, and 33 nurses. RESULTS: Nurses were much more likely than housestaff or attending physicians to cite inadequate communication as a reason for discharge delays. Nurses were also more likely to attribute delays to rounds and other conferences (48% vs. 22% and 9%, respectively; P = 0.05). Physicians, however, were more likely to cite delays in testing and availability of subacute care beds. Almost all housestaff and attendings thought that discharge decisions were generally made in the morning, and over 60% felt that discharge orders were usually written before noon. In contrast, none of the nurses thought that orders were usually written before noon. CONCLUSIONS: Caregivers at the same institution perceived different barriers to discharge and believed that discharge-related activities occurred at different times. To facilitate hospital discharge, communication gaps should be addressed and traditional morning routines should be reexamined. PMID- 11769298 TI - Effect of a self-management program on patients with chronic disease. AB - CONTEXT: For patients with chronic disease, there is growing interest in "self management" programs that emphasize the patients' central role in managing their illness. A recent randomized clinical trial demonstrated the potential of self management to improve health status and reduce health care utilization in patients with chronic diseases. OBJECTIVE: To evaluate outcomes of a chronic disease self-management program in a real-world" setting. STUDY DESIGN: Before after cohort study. PATIENTS AND SETTING: Of the 613 patients from various Kaiser Permanente hospitals and clinics recruited for the study, 489 had complete baseline and follow-up data. INTERVENTION: The Chronic Disease Self-Management Program is a 7-week, small-group intervention attended by people with different chronic conditions. It is taught largely by peer instructors from a highly structured manual. The program is based on self-efficacy theory and emphasizes problem solving, decision making, and confidence building. MAIN OUTCOME MEASURES: Health behavior, self-efficacy (confidence in ability to deal with health problems), health status, and health care utilization, assessed at baseline and at 12 months by self-administered questionnaires. RESULTS: At 1 year, participants in the program experienced statistically significant improvements in health behaviors (exercise, cognitive symptom management, and communication with physicians), self-efficacy, and health status (fatigue, shortness of breath, pain, role function, depression, and health distress) and had fewer visits to the emergency department (ED) (0.4 visits in the 6 months prior to baseline, compared with 0.3 in the 6 months prior to follow-up; P = 0.05). There were slightly fewer outpatient visits to physicians and fewer days in hospital, but the differences were not statistically significant. Results were of about the same magnitude as those observed in a previous randomized, controlled trial. Program costs were estimated to be about $200 per participant. CONCLUSIONS: We replicated the results of our previous clinical trial of a chronic disease self-management program in a "real-world" setting. One year after exposure to the program, most patients experienced statistically significant improvements in a variety of health outcomes and had fewer ED visits. PMID- 11769299 TI - A practice-based approach for converting from proton pump inhibitors to less costly therapy. AB - CONTEXT: Projected cost for lansoprazole, the formulary proton pump inhibitor (PPI) at our institution, was $1.8 million in 1999. While some patients require PPI therapy, many could control their symptoms with a histamine H2-receptor antagonist blocker (H2 blocker) at a much lower cost. OBJECTIVE: To evaluate a practice-based approach to converting patients from PPIs to H2 blockers. DESIGN: Before-after study. SETTING: Portland Veterans Affairs Primary Care Clinics. INTERVENTION: We developed guidelines and educated clinicians about the use of PPIs and H2 blockers. To help physicians convert appropriate patients from PPIs to H2 blockers, we gave them a list of their patients receiving PPIs, form letters for patients explaining the conversion, and structured prescription forms. Patient lists and e-mail reminders, as well as feedback on institutional performance, were sent to clinicians during the intervention period. OUTCOME MEASURES: Number of PPI and H2 prescriptions per enrollee and pharmacy costs. RESULTS: The average number of PPI prescriptions per enrollee at our institution decreased from 0.39 in the 9 months before the intervention to 0.27 in the 9 months after the intervention. The associated pharmacy costs decreased from an average of $43 to $28 per enrollee per quarter, a difference of $15 or a savings of $80,000 per quarter. Accounting for the decrease in medication prices during the study, this difference was $11 per patient per quarter, corresponding to a savings of about $60,000 per quarter. With respect to the conversion process, more than 70% of clinicians felt the intervention had a big impact on how they prescribed PPIs and H2 blockers. Eighty-two percent of clinicians converted patients from PPIs to H2 blockers during clinic time; 56% did so during administrative time. Overall, more clinicians considered the intervention to be helpful rather than a hassle. CONCLUSIONS: The number of PPI prescriptions decreased during the intervention and was sustained at least three quarters afterward. This low-intensity, practice-based intervention may serve as a model for other health care systems. PMID- 11769300 TI - Screening for diabetes mellitus in high-risk patients: cost, yield, and acceptability. AB - CONTEXT: Although universal screening for diabetes mellitus is generally not recommended, recent reports suggest that screening individuals with multiple diabetes risk factors may be worthwhile. Little is known about the cost, yield, or acceptability of this kind of screening. PRACTICE PATTERN EXAMINED: Screening of high-risk patients for diabetes mellitus using a two-step, glucose-based screening protocol: Patients were initially screened with a random glucose test; those with abnormal results received a follow-up fasting, 2-hour, 75-gram oral glucose tolerance test. CLINIC SELECTION: Three volunteer clinics from a large medical group in Minnesota. PATIENT SELECTION: Of 38,989 adults receiving care at the three clinics, we identified 1548 high-risk patients with evidence of both dyslipidemia and hypertension in laboratory and administrative databases. Many of these 1548 patients were not eligible for screening: Twenty-five percent already had diagnosed diabetes; 41% had been screened for diabetes in the past year; and 3% had died, disenrolled, or changed clinics before screening commenced. The remaining 30% (n = 469) were invited for diabetes screening. RESULTS: Of the 469 high-risk patients invited, 206 (44%) initiated screening; 176 (38%) completed diabetes screening. Five new patients with diabetes were identified in this high risk group (one from the random glucose test and four from the glucose tolerance test). One new patient with diabetes was identified for every 40 high-risk patients screened. The program cost $4064 per new case of diabetes identified (screening costs alone). CONCLUSION: In this high-risk managed care population, the yield and acceptability of systematic diabetes screening were low, and the costs were relatively high. The acceptability of office-based diabetes screening may be improved by using a one-step screening test, such as glycosylated hemoglobin, during routine visits. PMID- 11769301 TI - Quality improvement can't be optional. PMID- 11769302 TI - Finding undiagnosed type 2 diabetes: is it worth the effort? PMID- 11769303 TI - Primer on type I and type II errors. PMID- 11769304 TI - Effects of hippocampal lesions on delayed nonmatching-to-sample in monkeys: a reply to Zola and Squire (2001). PMID- 11769305 TI - Phase precession and phase-locking of hippocampal pyramidal cells. AB - We propose that the activity patterns of CA3 hippocampal pyramidal cells in freely running rats can be described as a temporal phenomenon, where the timing of bursts is modulated by the animal's running speed. With this hypothesis, we explain why pyramidal cells fire in specific spatial locations, and how place cells phase-precess with respect to the EEG theta rhythm for rats running on linear tracks. We are also able to explain why wheel cells phase-lock with respect to the theta rhythm for rats running in a wheel. Using biophysically minimal models of neurons, we show how the same network of neurons displays these activity patterns. The different rhythms are the result of inhibition being used in different ways by the system. The inhibition is produced by anatomically and physiologically diverse types of interneurons, whose role in controlling the firing patterns of hippocampal cells we analyze. Each firing pattern is characterized by a different set of functional relationships between network elements. Our analysis suggests a way to understand these functional relationships and transitions between them. PMID- 11769306 TI - Competitive Hebbian learning and the hippocampal place cell system: modeling the interaction of visual and path integration cues. AB - The hippocampus has long been thought essential for implementing a cognitive map of the environment. However, almost 30 years since place cells were found in rodent hippocampal field CA1, it is still unclear how such an allocentric representation arises from an ego-centrically perceived world. By means of a competitive Hebbian learning rule responsible for coding visual and path integration cues, our model is able to explain the diversity of place cell responses observed in a large set of electrophysiological experiments with a single fixed set of parameters. Experiments included changes observed in place fields due to exploration of a new environment, darkness, retrosplenial cortex inactivation, and removal, rotation, and permutation of landmarks. To code for visual cues for each landmark, we defined two perceptual schemas representing landmark bearing and distance information over a linear array of cells. The information conveyed by the perceptual schemas is further processed through a network of adaptive layers which ultimately modulate the resulting activity of our simulated place cells. In path integration terms, our system is able to dynamically remap a bump of activity coding for the displacement of the animal in relation to an environmental anchor. We hypothesize that path integration information is computed in the rodent posterior parietal cortex and conveyed to the hippocampus where, together with visual information, it modulates place cell activity. The resulting network yields a more direct treatment of partial remapping of place fields than other models. In so doing, it makes new predictions regarding the nature of the interaction between visual and path integration cues during new learning and when the system is challenged with environmental changes. PMID- 11769307 TI - Role of long-term synaptic modification in short-term memory. AB - One way that some types of short-term or working memory may be implemented in the brain is by using autoassociation networks that recirculate information to maintain the firing of a subset of neurons in what is termed an attractor state. We describe how long-term synaptic modification is necessary to set up the appropriate stable attractors, each one of which corresponds to a memory of a particular item. Once the synapses have been modified, any of the short-term memory states may be triggered by an appropriate input which starts the neurons firing in one of the attractors, and then the firing is maintained in that attractor by the already modified synapses, with no further synaptic modification necessary. This analysis leads to the prediction that if this type of implementation is used for working memory, then long-term synaptic modification may be necessary only during an acquisition phase of a task, and once the task has been acquired, the performance of the working memory task should be unimpaired if no further synaptic modification is allowed. We show that a considerable body of research findings on the effects of agents that block synaptic modification on working memory tasks can be understood in this way. Many of the findings are consistent with the hypothesis that blocking synaptic modification in the hippocampus impairs the acquisition, but not the later performance, of hippocampal-dependent working memory tasks. PMID- 11769308 TI - Computational model of carbachol-induced delta, theta, and gamma oscillations in the hippocampus. AB - Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of activity, including delta (0.5-2 Hz), theta (4-12 Hz), and gamma (30-80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the delta (CCH delta), theta (CCH-theta), and gamma (CCH-gamma) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-theta, synchronous CCH delta, and synchronous CCH-theta with increasing CCH concentration (Fellous and Seinowski, Hippocampus 2000;1 0:187-197). In a network model of area CA3, the time scale for CCH-delta corresponded to the decay constant of the gating variable of the calcium-dependent potassium (K-AHP) current, that of CCH-theta to an intrinsic subthreshold membrane potential oscillation of the pyramidal cells, and that of CCH-gamma to the decay constant of GABAergic inhibitory synaptic potentials onto the pyramidal cells. In model simulations, the known physiological effects of carbachol on the muscarinic and K-AHP currents, and on the strengths of excitatory postsynaptic potentials, reproduced transitions from asynchronous CCH-theta to CCH-delta and from CCH-delta to synchronous CCH-theta. The simulations also exhibited the interspersed CCH-gamma/CCH-delta and CCH gamma/CCH-theta that were observed in experiments. The model, in addition, predicted an oscillatory state with all three frequency bands present, which has not yet been observed experimentally. PMID- 11769309 TI - Dorsal hippocampal kindling selectively impairs spatial learning/short-term memory. AB - Kindling with electrical stimulation of the dorsal hippocampus has been shown to disrupt spatial task performance in rats. The present study investigated the specificity of this effect in terms of the possible contribution of nonmnemonic effects, the presence of a more general mnemonic deficit, and the involvement of learning/short-term memory and/or long-term memory processes. Rats were fully kindled with stimulation of the dorsal hippocampus and subsequently tested for acquisition, 7-day retention, and 28-day retention of a hidden platform (HP) location in the Morris water maze and an object discrimination problem in a modified water maze. To control for nonmnemonic behavioral impairments, testing on both tasks was preceded by training on visible platform control tasks. Kindling impaired acquisition of the HP location but spared performance on all other aspects of testing, indicating a specific impairment of spatial learning/short-term memory. These results suggest that epileptogenesis induced by hippocampal stimulation is indeed associated with a selective disruption of the mechanisms mediating spatial learning/short-term memory. PMID- 11769310 TI - Aberrant synaptic transmission in the hippocampal CA3 region and cognitive deterioration in protein-repair enzyme-deficient mice. AB - L-aspartate is the amino-acid residue most susceptible to spontaneous isomerization. This denaturation causes an alteration in the biological activity of the protein and is regarded as an aging process of the protein. Protein L isoaspartyl methyltransferase (PIMT) repairs this post-translational modification and thus is implicated in retarding the aging process of proteins. PIMT is highly expressed in the brain, and its deficiency results in progressive epilepsy after 4 weeks of age, with a fatal seizure in mice. Here we report the pathophysiological role of this repair system in the hippocampal slice of PIMT deficient mice. The hippocampal mossy fiber-CA3 synapses of PIMT-deficient mice showed hyperexcitation that was repressed by a gamma-aminobutyric acid (GABA)A receptor agonist muscimol. In addition, the mossy fiber-CA3 synapses failed to show long-term potentiation or paired-pulse facilitation. No abnormality, however, was observed in Schaffer collateral-CA1 synapses or in perforant path dentate gyrus synapses. Electron microscopic study revealed aberrant distribution of synaptic vesicles in the mossy fiber terminals and vacuolar degeneration at the axon hillock of dentate granule cells in PIMT-deficient mice. Furthermore, the PIMT-deficient mice showed impaired spatial memory in Morris water maze test and exhibited fewer anxiety-related behaviors in the elevated-plus test. These results suggest that the mossy fiber-CA3 system is vulnerable to aspartate isomerization and that the PIMT-mediated repair system is essential for maintenance of normal functions of the hippocampus. PMID- 11769311 TI - Is mossy fiber sprouting present at the time of the first spontaneous seizures in rat experimental temporal lobe epilepsy? AB - The contribution of mossy fiber sprouting to the generation of spontaneous seizures in the epileptic brain is under dispute. The present study addressed this question by examining whether sprouting of mossy fibers is present at the time of appearance of the first spontaneous seizures in rats, and whether all animals with increased sprouting have spontaneous seizures. Epileptogenesis was induced in 16 rats by electrically stimulating the lateral nucleus of the amygdala for 20-30 min until the rats developed self-sustained status epilepticus (SSSE). During and after SSSE, rats were monitored in long-term by continuous video-electroencephalography until they developed a second spontaneous seizure (8 54 days). Thereafter, monitoring was continued for 11 days to follow seizure frequency. The density of mossy fiber sprouting was analyzed from Timm-stained preparations. The density of hilar neurons was assessed from thionin-stained sections. Of 16 rats, 14 developed epilepsy. In epileptic rats, the density of mossy fiber sprouting did not correlate with the severity or duration (115-620 min) of SSSE, delay from SSSE to occurrence of first (8-51 days) or second (8-54 days) spontaneous seizure, or time from SSSE to perfusion (20-63 days). In the temporal end of the hippocampus, the sprouting correlated with the severity of neuronal damage (ipsilateral: r = -0.852, P < 0.01 contralateral: r = -0.748, P < 0.01). The two animals without spontaneous seizures also had sprouting. Increased density of sprouting in animals without seizures, and its association with the severity of neuronal loss was confirmed in another series of 30 stimulated rats that were followed-up with video-EEG monitoring for 60 d. Our data indicate that although mossy fiber sprouting is present in all animals with spontaneous seizures, its presence is not necessarily associated with the occurrence of spontaneous seizures. PMID- 11769312 TI - Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy. AB - A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE. PMID- 11769313 TI - Beta-adrenergic blockade in the dentate gyrus in vivo prevents high frequency induced long-term potentiation of EPSP slope, but not long-term potentiation of population spike amplitude. AB - High frequency (HF)-induced and norepinephrine (NE)-induced long-term potentiation have been hypothesized to utilize common mechanisms of induction and expression in the dentate gyrus. In vitro data tend to support this hypothesis, but few studies have been done in vivo. The present study records perforant path evoked potentials simultaneously on two micropipettes, one filled with saline and the other with the beta-antagonist, timolol. Stimulation of the paragigantocellularis nucleus (PGi) was used as a method of producing NE release in the dentate gyrus, and thus, to assess the efficacy of beta-receptor blockade on the timolol pipette. Beta-blockade by timolol attenuated PGi-induced spike potentiation. HF-induced potentiation of the excitatory post-synaptic potential (EPSP) slope was also blocked by timolol, but HF-induced spike amplitude potentiation was unaffected. These results are consistent with an earlier report examining HF-long-term potentiation (LTP) following 6-OHDA-induced NE depletion, which showed that the EPSP slope LTP depended, for its full expression, on NE, but potentiation of the population spike amplitude component of HF-induced LTP did not. In the present study, PGi-induced potentiation of spike amplitude on the saline pipette was normal after HF-induced saturation of spike amplitude potentiation, suggesting that the mechanisms for expression of spike potentiation, as well as induction of spike potentiation, are separate for HF and NE stimulation. PMID- 11769314 TI - Chronic psychosocial stress regulates the expression of both GR and MR mRNA in the hippocampal formation of tree shrews. AB - A persistent hyperactivity of the hypothalamic-pituitary-adrenal axis and thus elevated glucocorticoid levels are main neuroendocrine features of depressive symptomatology in humans. The broad range of effects that are set off by glucocorticoids is mediated by glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which themselves are subject to autoregulation. In order to investigate the impact of long-lasting psychological stress on corticosteroid receptor mRNA expression in the hippocampal formation, we employed the psychosocial stress paradigm in male tree shrews (Tupaia belangeri). By in situ hybridization studies and semiquantitative evaluation of stress-induced changes of GR and MR mRNA expression at the single-cell level, brain tissue from subordinate animals which were exposed to 27 days (1 h/day) of social confrontation was compared to that of nonstressed animals. Four weeks of stress exposure resulted in a downregulation of GR mRNA in the dentate gyrus and hippocampal subfields CA1 and CA3 of subordinate male tree shrews compared to controls. The MR mRNA content in these subfields of the anterior hippocampus was also clearly reduced. On the contrary, in a more posterior location on the longitudinal axis of the tree shrew hippocampus, the MR message was increased in subfields CA1 and CA3 and in the dentate gyrus. These results suggest a relevance of the stress-induced regulation of both corticosteroid receptor subtype mRNAs in a naturalistic challenging situation. Moreover, the differential regulation of MR mRNA along the rostrocaudal axis of the hippocampus adds another feature to the heterogenous composition of this structure. PMID- 11769315 TI - An improved model for determining degree-day values from daily temperature data. AB - Although using hourly weather data offers the greatest accuracy for estimating growing degree-day values, daily maximum and minimum temperature data are often used to estimate these values by approximating the diurnal temperature trends. This paper presents a new empirical model for estimating the hourly mean temperature. The model describes the diurnal variation using a sine function from the minimum temperature at sunrise until the maximum temperature is reached, another sine function from the maximum temperature until sunset, and a square root function from then until sunrise the next morning. The model was developed and calibrated using several years of hourly data obtained from five automated weather stations located in California and representing a wide range of climate conditions. The model was tested against an additional data-set at each location. The temperature model gave good results, the rootmean-square error being less than 2.0 degrees C for most years and locations. The comparison with published models from the literature showed that the model was superior to the other methods. Hourly temperatures from the model were used to calculate degree-day values. A comparison between degree-day estimates determined from the model and those obtained other selected methods is presented. The results showed that the model had the best accuracy in general regardless of the season. PMID- 11769316 TI - An analysis of relationships among plant community phenology and seasonal metrics of Normalized Difference Vegetation Index in the northern part of the monsoon region of China. AB - This study focuses on relationships between the phenological growing season of plant communities and the seasonal metrics of Normalized Difference Vegetation Index (NDVI) at sample stations and pixels overlying them, and explores the procedure for determining the growing season of terrestrial vegetation at the regional scale, using threshold NDVI values obtained by surface-satellite analysis at individual stations/pixels. The cumulative frequency of phenophases has been calculated for each plant community and each year in order to determine the growing season at the three sample stations from 1982 to 1993. The precise thresholds were arbitrarily set as the dates on which the phenological cumulative frequency reached 5% and 10% (for the beginning) and 90% and 95% (for the end). The beginning and end dates of the growing season were then applied each year as time thresholds, to determine the corresponding 10-day peak greenness values from NDVI curves for 8-km2 pixels overlying the phenological stations. According to a trend analysis, a lengthening of the growing seasons and an increase of the integrated growing season NDVI have been detected in the central part of the research region. The correlation between the beginning dates of the growing season and the corresponding threshold NDVI values is very low, which indicates that the satellite-sensor-derived greenness is independent of the beginning time of the growing season of local plant communities. Other than in spring, the correlation between the end dates of the growing season and the corresponding threshold NDVI values is highly significant. The negative correlation shows that the earlier the growing season terminates, the larger the corresponding threshold NDVI value, and vice versa. In order to estimate the beginning and end dates of the growing season using the threshold NDVI values at sites without phenological data from 1982 to 1993, we calculated the spatial correlation coefficients between NDVI time-series at each sample station and other contiguous sites year by year. The results provide the spatial extrapolation area of the growing season for each sample station. Thus, we can use the threshold NDVI value obtained at one sample station/pixel for a year to determine the growing season at the extrapolation sites with a similar vegetation type for the same year. PMID- 11769317 TI - Temperature data for phenological models. AB - In an arid environment, the effect of evaporation on energy balance can affect air temperature recordings and greatly impact on degree-day calculations. This is an important consideration when choosing a site or climate data for phenological models. To our knowledge, there is no literature showing the effect of the underlying surface and its fetch around a weather station on degree-day accumulations. In this paper, we present data to show that this is a serious consideration, and it can lead to dubious models. Microscale measurements of temperature and energy balance are presented to explain why the differences occur. For example, the effect of fetch of irrigated grass and wetting of bare soil around a weather station on diurnal temperature are reported. A 43-day experiment showed that temperature measured on the upwind edge of an irrigated grass area averaged 4% higher than temperatures recorded 200 m inside the grass field. When the single-triangle method was used with a 10 degrees C threshold and starting on May 19, the station on the upwind edge recorded 900 degree-days on June 28, whereas the interior station recorded 900 degree-days on July 1. Clearly, a difference in fetch can lead to big errors for large degree-day accumulations. Immediately after wetting, the temperature over a wet soil surface was similar to that measured over grass. However, the temperature over the soil increased more than that over the grass as the soil surface dried. Therefore, the observed difference between temperatures measured over bare soil and those over grass increases with longer periods between wettings. In most arid locations, measuring temperature over irrigated grass gives a lower mean annual temperature, resulting in lower annual cumulative degree-day values. This was verified by comparing measurements over grass with those over bare soil at several weather stations in a range of climates. To eliminate the effect of rainfall frequency, using temperature data collected only over irrigated grass, is recommended for long-term assessment of climate change effects on degree-day accumulation. In high evaporative conditions, a fetch of at least 100 m of grass is recommended. Our results clearly indicate that weather stations sited over bare soil have consistently higher degree-day accumulations. Therefore, especially in arid environments, phenology models based on temperature collected over bare soil are not transferable to those based on temperature recorded over irrigated grass. At a minimum, all degree-day-based phenology models reported in the literature should clearly describe the weather station site. PMID- 11769318 TI - Higher northern latitude normalized difference vegetation index and growing season trends from 1982 to 1999. AB - Normalized difference vegetation index data from the polar-orbiting National Oceanic and Atmospheric Administration meteorological satellites from 1982 to 1999 show significant variations in photosynthetic activity and growing season length at latitudes above 35 degrees N. Two distinct periods of increasing plant growth are apparent: 1982-1991 and 1992-1999, separated by a reduction from 1991 to 1992 associated with global cooling resulting from the volcanic eruption of Mt. Pinatubo in June 1991. The average May to September normalized difference vegetation index from 45 degrees N to 75 degrees N increased by 9% from 1982 to 1991, decreased by 5% from 1991 to 1992, and increased by 8% from 1992 to 1999. Variations in the normalized difference vegetation index were associated with variations in the start of the growing season of -5.6, +3.9, and -1.7 days respectively, for the three time periods. Our results support surface temperature increases within the same period at higher northern latitudes where temperature limits plant growth. PMID- 11769319 TI - Use of bioclimatic indexes to characterize phenological phases of apple varieties in Northern Italy. AB - The research was designed to characterize the phenological behaviour of different apple varieties and to compare different bioclimatic indexes in order to evaluate their adaptability in describing the phenological phases of fruit species. A field study on the requirement for chilling units (winter chilling requirement) and the accumulation of growing degree hours of 15 native apple cultivars was carried out in a fruit-growing area in North West Italy (Cuneo Province, Piedmont). From 1991 to 1993, climatic data were collected at meteorological stations installed in an experimental orchard (Verzuolo, Cuneo). Four methods were compared to determine the winter chilling requirement: Hutchins, Weinberger Eggert, Utah and North Carolina. The Utah method was applied to determine the time when the chilling units accumulated become effective in meeting the rest requirements. A comparison of the different methods indicated that the Weinberger Eggert method is the best: as it showed the lowest statistical variability during the 3 years of observations. The growing degree hour requirement (GDH) was estimated by the North Carolina method with two different base temperatures: 4.4 degrees C and 6.1 degrees C. More difficulties were met when the date of rest completion and the beginning of GDH accumulation was determined. The best base temperature for the estimation of GDH is 4.4 degrees C. Phenological and climatic characterizations are two basic tools for giving farmers and agricultural advisors important information about which varieties to choose and which are the best and the most correct cultivation practices to follow. PMID- 11769320 TI - Phenological modifications in plants by various edaphic factors. AB - Various mechanical, chemical and physical soil analyses were carried out, in addition to weather observations, for 3 years at several sites along an oceanic continental gradient in a fjord district in western Norway. All the environmental factors observed were correlated with the spring and a few late-season phenophases of many native and cultivated woody plants and some herbs by simple, linear correlations and by stepwise multiple and partial analyses. Different techniques were used to try and eliminate many intercorrelations between various environmental factors. As expected, air temperature measurements in nearly all analyses from these temperate region districts gave the most significant correlations with the phenology of the plants, the temperature during the night generally being the most important in mainly vegetative periods, e.g. to leaf bud break in spring, and the temperature during the day affecting the more generative phases, such as the period between leaf bud break and flowering. The other environmental factors, however, showed strong variation in correlation significance among the various species studied and also with different phenophases of the same species. Various hypotheses are put forward to explain such variation. Air humidity (including precipitation) and/or soil moisture (including intercorrelated parameters, e.g. soil grain size and bulk density) were relatively often found to be of importance. In the stepwise multiple analyses for leaf bud break of the birch (Betula pubescens), for instance, the amount of precipitation was the second factor to enter the analyses by a positive correlation with the developmental rate, after the most important factor, the night temperature. Positive correlations with a high clay content and bulk density in the soil indicated that high soil moisture is also favourable for early bud break in the birch. Other phenophases that seemed to be favoured by a good water supply were leaf bud break of the bird cherry (Prunus padus) and rowan (Sorbus aucuparia), and flowering of the hazel (Corylus avellana), common lilac (Syringa vulgaris), plum ('Victoria') and currant ('Red Dutch') and also, to some degree, the goat willow (Salix caprea). The amount of ions (P, K, Mg and Ca) often showed negative correlations with the developmental rate, particularly of earlier phenophases of both native and cultivated plants (except for the apple 'Gravenstein' and pear 'Moltke'), possibly, indicating that a high nutrient level delayed plant development. A similar explanation might be given for the observation that high pH in the soil often seemed to delay plant development (leaf bud break of Betula, Sorbus, Syringa and plum, and flowering of Corylus, bluebell (Campanula rotundifolia) and red currant). According to the analyses there seemed to be a tendency for plants that are particularly dependent on warm weather for leaf bud break, e.g. the ash (Fraxinus excelsior), and flowering, e.g. Prunus, pear, apple and, to some degree, the raspberry ('Preussen'), to be less dependent on other environmental factors for their development. For instance, if there were any effects of water for these plants, they were negative for moisture and soil factors intercorrelated with water. PMID- 11769321 TI - Phytophenological trends in Switzerland. AB - Nation-wide phenological observations have been made in Switzerland since 1951. In addition to these observation programmes, there are two very long phenological series in Switzerland: leaf bud burst of horse-chestnut trees has been observed in Geneva since 1808 and full flowering of cherry trees in Liestal since 1894. In addition to the presentation of these two long phenological series, trends for 896 phenological time series have been calculated with national data from 1951 to 1998. The earlier bud burst of horse-chestnut trees in Geneva can be attributed mainly to the city effect (warmth island). This phenomenon was not observed with the cherry tree flowering in Liestal. A clear trend towards earlier appearance dates in spring and a weak tendency towards later appearance dates in autumn could be shown with data from the national observation network. It must be noted that different phenophases and plant species react differently to various environmental influences. PMID- 11769322 TI - Museum egg collections as stores of long-term phenological data. AB - Museum collections hold large amounts of data on collecting dates and localities of eggs collected over the past 150 years. Egg collections hold the longest available time series for a wide range of bird species on a large spatial scale. Using data for two British species I investigate whether egg collection data can be used in phenological research. A method is presented allowing laying dates to be estimated from collecting dates. Problems and biases in the data are highlighted. Both the dipper and song thrush have started laying earlier over the past 150 years. The advance in laying is significantly correlated with mean March temperature. PMID- 11769323 TI - The effects of temperature, altitude and latitude on the arrival and departure dates of the swallow Hirundo rustica in the Slovak Republic. AB - The (barn) swallow Hirundo rustica is a traditional harbinger of spring in many countries of the Northern Hemisphere. This paper uses information on the arrival and departure dates of the swallow in the Slovak Republic for the 30 years 1961 1985 and 1996-2000. Records were taken at 19 locations throughout the Republic representing an altitude range from 105 m to 760 m. Monthly temperature data were constructed from six meteorological stations. With the use of regression techniques, trends towards later arrival, earlier departure and the effects of latitude, altitude and temperature are all apparent. PMID- 11769324 TI - Is the detection of the first arrival date of migrating birds influenced by population size? A case study of the red-backed shrike Lanius collurio. AB - Many analyses do not consider the problems associated with the effects of population size on encounter recording. Population size could impact on the detection of bird arrival time as there is a higher probability of observing earlier arrival when the population size is greater and the song activity of birds is increased, as occurs with a larger population. As a case study, we have analysed data on the red-backed shrike Lanius collurio collected in Western Poland during 1983-2000. In this period the red-backed shrike's return to its breeding sites became significantly earlier whilst the contemporary population size increased significantly. To eliminate linear trends through time we have worked on the standardised residuals from regression of both arrival time and population size on year. The correlation between arrival time and population size residuals was significantly negative, further supporting the link between detection and population size. This finding suggests that, in studies of avian migration and its changes over time, the relationship between arrival date and population size needs to be considered. PMID- 11769325 TI - Effects of voltage-sensitive calcium channel blockers on extracellular dopamine levels in rat striatum. AB - Various subtypes of voltage-sensitive calcium channels (VSCCs) support the release of dopamine (DA) in the central nervous system. Using in vivo microdialysis, we investigate the influence of these subtypes of calcium channels on dopaminergic terminals in the rat striatum. L-type (nifedipine-sensitive), N type (omega-conotoxin GVIA-sensitive), or N- and P/Q-type (omega-conotoxin MVIIC sensitive) Ca2+ channels were blocked using selective antagonists injected locally, and K+-evoked DA release was measured in freely moving animals. K+ (100 mM) induced a massive increase of basal DA extracellular levels (930%) and was without significant effect on extracellular levels of DA metabolites DOPAC and HVA, and on the serotonin metabolite 5HIAA. Omega-conotoxin GVIA (1 microM) and omega-conotoxin MVIIC (1 microM) significantly reduced the K+-evoked DA release by 55 and 62%, respectively. The simultaneous application of the two conotoxins at the same concentration reduced K+-evoked DA release by 66%. Nifedipine (10 microM) had no significant effect on K-evoked DA release, while neomycin, a nonspecific VSCC blocker, produced a highly significant decrease when applied at 250 and 500 microM (56 and 75%, respectively). The compounds. however, had no effect on basal DA release and on the levels of extracellular DOPAC, HVA, and 5HIAA. These results suggest that under high and persistent conditions of membrane depolarization (15 min, 10 mM K+), striatal DA release is mainly mediated by N-type VSCCs. PMID- 11769326 TI - NMDA-stimulated Ca2+ uptake into barrel cortex slices of spontaneously hypertensive rats. AB - The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit hyperactivity disorder (ADHD), since it has behavioural characteristics that resemble the behavioral disturbances of ADHD, namely hyperactivity, failure to sustain attention, and impulsiveness. The aim of this study was to establish whether N-methyl-D-aspartate (NMDA) receptor function was altered in barrel cortex slices of 4- to 6- week-old SHR compared to their normotensive Wistar Kyoto (WKY) control rats. The barrel cortex was dissected from brain slices corresponding to antero-posterior coordinates 8.7-4.8 mm with reference to the Paxinos and Watson (1986) atlas and divided into rostral, middle, and caudal regions. 45Ca2+ uptake was stimulated by incubating test slices in buffer containing 100 microM NMDA for 2 min at 35 degrees C. Total 45Ca2+ uptake into the entire barrel cortex as well as uptake into all regions of SHR barrel cortex was lower compared to WKY. Basal uptake into the entire barrel cortex as well as uptake into rostral and caudal regions of SHR barrel cortex was lower than WKY but basal uptake into the middle region was the same for both strains. There was no difference between SHR and WKY in NMDA-stimulated 45Ca2+ uptake into barrel cortex slices except for significantly lower NMDA-stimulated uptake into the middle region of SHR barrel cortex compared to WKY. These findings suggest that calcium metabolism is disturbed in the somatosensory cortex of SHR but that NMDA receptor function is not altered. PMID- 11769327 TI - Increased AMPA receptor function in slices containing the prefrontal cortex of spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) are used as a genetic model for attention deficit hyperactivity disorder (ADHD), since they have behavioral characteristics that mimic the major symptoms of ADHD. We have previously shown that dopaminergic and noradrenergic systems are altered in the prefrontal cortex of SHR compared to normotensive Wistar-Kyoto (WKY) control rats. We also showed that neural circuits that use glutamate as a neurotransmitter increased norepinephrine release from rat prefrontal cortex slices and that glutamate caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from those of WKY. The effect of glutamate did not appear to be mediated by NMDA receptors, since NMDA did not exert any effect on norepinephrine release and the NMDA receptor antagonist MK-801 did not reduce the effect of glutamate. In this investigation we show that the stimulatory effect of glutamate is greater in SHR than in WKY and that the effect can be antagonised by the alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX). The results suggest that glutamatergic neuron terminals in rat prefrontal cortex establish synaptic contacts with noradrenergic terminals to enhance norepinephrine release by activation of AMPA receptors and that this enhancement is amplified in SHR. PMID- 11769328 TI - Neurochemistry of superficial spinal neurones projecting to nucleus of the solitary tract that express c-fos on chemical somatic and visceral nociceptive input in the rat. AB - We have investigated the presence of three neurochemical markers, glutamate, calbindin-D28k, and nitric oxide synthase, in spinal neurones that transmit chemical noxious inputs from both the skin and the viscera, by combining retrograde labelling with the fluorescent tracer Fluorogold with dual labelling immunohistochemistry. Neurones projecting to the nucleus of the solitary tract (NTS) that expressed Fos protein in response to cutaneous or visceral noxious stimulation were concentrated in lamina I of the cervical and lumbosacral segments, respectively. Although both labelled neuronal populations were numerous, the spino-solitary cells that transmit visceral nociceptive input predominated over those transmitting cutaneous nociceptive input. Calbindin-D28k immunoreactivity was observed in neurones of three morphological types (fusiform, flattened, and pyramidal) projecting to the NTS that were activated by somatic or visceral nociceptive neurones. Nitric oxide synthase and glutamate immunoreactivities were present only in viscerally activated nociceptive neurones projecting to the NTS. Glutamate-immunopositive NTS-projecting cells were exclusively of the flattened type, and the nitric oxide synthase-immunolabelled NTS-projecting cells comprised 75%/fusiform cells and 25% flattened cells. These data suggest that the involvement of excitatory spinal lamina I projection neurones in the transmission of peripheral chemical nociceptive inputs to the NTS may be restricted to information of visceral origin. PMID- 11769329 TI - Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP212 cells. AB - The human neuroblastoma cell line CHP212 was found to express functional high affinity neurotensin (NTS-1) receptor subtype. Based on the functional interactions between neurotensin and dopamine transmission, we have used this cell line to investigate the short- and long-term modulation of tyrosine hydroxylase gene expression by the stable neurotensin agonist JMV 449. After exposure of the cells to 1 microM JMV 449 for 5 or 72 h, tyrosine hydroxylase protein and mRNA levels were significantly increased as detected by western blot analysis and quantitative RT-PCR, respectively. Transfection of CHP212 cells with a plasmid containing the luciferase reporter gene under the control of a limited proximal region of the cloned tyrosine hydroxylase promoter, revealed that the effect of JMV 449 results from an increase in the transcriptional activity of the TH gene. These results indicate that modulation of tyrosine hydroxylase gene expression may constitute one of the mechanisms involved in the control of dopamine transmission by neurotensin. Such neurotensin-mediated changes in tyrosine hydroxylase expression may also participate in multiple adaptation processes within the central nervous system to environmental conditions where neurotensin is released such as stress and food intake. PMID- 11769330 TI - The role of the MAP-kinase superfamily in beta-amyloid toxicity. AB - The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. These stimuli include growth factor binding to its receptor as well as stressful situations such as hypoxia and oxidative stress. It has been postulated that one of the mechanisms by which beta-amyloid exerts its toxic effects is to produce oxidative stress. This study therefore investigated whether the MAP-kinase pathway was activated in cells following exposure to beta-amyloid. Neuroblastoma (N2alpha) cells were used in all experiments. The cells were exposed to 50, 100, and 500 microM glutamate, and 10, 30, and 50 microM beta-amyloid, for 24 h. The methylthiazolyl tetrazolium salt (MTT) assay was performed to determine the degree of toxicity. The generation of hydrogen peroxide was detected by fluorescence microscopy using the dye dihydrochlorofluorescein diacetate (DCDHF). Extracellular-signal-regulated kinase (ERK) and p38 MAP-kinase phosphorylation, as representatives of the MAP-kinase pathway, was determined. Treating N2alpha cells with beta-amyloid resulted in a greater than 50% reduction in cell viability. These cells also showed a significantly higher presence of hydrogen peroxide. Western Blot analysis revealed that the phosphorylation of p38 MAP kinase was dose-dependently increased in cells exposed to glutamate and beta amyloid. On the other hand, the phosphorylation of ERK was significantly reduced in these cells. These data therefore suggest that the toxic effects of beta amyloid involve the generation of hydrogen peroxide, leading to the activation of p38 and the down-regulation of ERK. PMID- 11769332 TI - The effect of copper on (3H)-tryptophan metabolism in organ cultures of rat pineal glands. AB - Copper toxicity has been implicated in various neurodegenerative disorders such as Wilson's disease and Alzheimer's disease. Free copper in the brain is toxic and leads to neuronal and cellular damage, through free radical generation. Melatonin has been investigated as a possible copper ion chelator. Melatonin could prevent copper-induced neuronal and cellular damage through binding with copper and preventing copper-induced free radical generation. The effect of copper on pineal indolamine synthesis has not been studied extensively. In the present study, copper (2 mg/kg) and melatonin (12 mg/kg) were administered daily to Wistar rats for a 2-week and 6-week period. Pineal organ culture was utilized to monitor pineal indolamine synthesis. The pineals from the 2-week copper/melatonin-treated group showed a statistically significant decrease in 5 methoxytryptophol synthesis (p < 0.01), compared to the pineals from the copper treated group. Conversly, in the 6-week experiment, 5-methoxytryptophol synthesis was increased in both the copper- and copper/melatonin-treated groups. There was a statistically significant decrease in the N-acetyl serotonin level in the pineals from the 6-week copper-treated animals, as compared to the control- and copper/melatonin-treated group (p < 0.01). These results imply that copper reduces N-acetyltransferase activity, which results in a decrease in N-acetyl serotonin synthesis. Melatonin when coadministered with copper appears to prevent the N-acetyltransferase inhibition by copper. Copper exerts contradictory effects on 5-methoxytryptophol synthesis. Further investigations need to be carried out to examine the effects of copper on the pineal enzymes. PMID- 11769331 TI - 17Beta-estradiol attenuates quinolinic acid insult in the rat hippocampus. AB - A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol quinolinic acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM 5 microM 17beta-estradiol or quinolinic acid. The results show that 17beta estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D aspartate (NMDA) receptor. This would result in a decrease in intracellular free calcium influx and resultant neuronal swelling. PMID- 11769333 TI - Cellular distribution of endothelin-1 mRNA in human brain by in situ RT-PCR. AB - Endothelins (ETs) are a family of potent vasoconstrictor and comitogenic polypeptides consisting of 21-amino acids. Using in situ hybridization, ET-1 mRNA has previously been localized to neuronal cell bodies in fourteen human brain regions. However, because in situ hybridization has a limited detection sensitivity of 20 mRNA copies per cell, ET-1 mRNA may be present in previously undetected areas. Hence, our objective was to localize ET-1 mRNA in specific human brain regions and astrocytic tumours using the more sensitive in situ reverse transcriptase polymerase chain reaction (in situ RT-PCR). Human brain autopsy tissue and surgical cerebral tumour tissue were treated with proteinase K and DNase, followed by RT-PCR using primers specific for ET-1 mRNA and digoxygenin-labelled dUTP in the PCR mixture. The DIG-dUTP was localized with an immunodetection system. We demonstrate ET-1 mRNA labelling in twenty two of the twenty four brain regions studied including those regions in which ET-1 mRNA has been observed by in situ hybridization. In addition, the localization of ET-1 mRNA observed in astrocytomas suggests a role for ET-1 in tumour pathogenesis. In situ RT-PCR has proven to be highly sensitive in its ability to detect low mRNA expression at the cellular level. Our results confirm a role for ET-1 in the human nervous system. PMID- 11769334 TI - Differences in protein expression in the subcommissural organ of normal and lordotic lizards (Agama impalearis). AB - Lordosis, a skeletal malformation, is characterized by abnormal curvature of the vertebral column. Involvement of the subcommissural organ (SCO) in the correct development of the axial skeleton via the thread-like Reissner's fiber (RF) has been suggested. However, the functional significance of the SCO and RF in these mechanisms remains, to date, little understood. To detect eventual changes in the SCO of reptiles bearing a naturally occurring skeletal malformation, we aimed here at investigating with immunohistochemistry RF glycoprotein and immediate early gene expression in the SCO of normal and lordotic lizards. In normal lizards, RF immunoreactivity was evident in the apical and basal domains of SCO cells. In specimens derived from lordotic animals, RF-immunoreactive material filled all SCO cell portions, and numerous large droplets were observed in the basal part of the organ. Cell nuclei exhibiting immunoreactivity to the protein product of the gene c-fos were evident in basal SCO cells of lordotic animals, whereas Fos immunoreactivity was absent in the SCO of normal lizards. The changes detected in RF immunoreactivity and Fos induction in SCO cells of lordotic animals favor the occurrence of changes in the secretory activity and gene expression of SCO cells. The present data further demonstrate modifications occurring in the SCO secretory material in skeletal malformed vertebrates, and support a relationship of such changes with the malformed state of these animals. PMID- 11769335 TI - Clinical diagnosis of malaria on the Thai-Myanmar border. AB - BACKGROUND: To evaluate the prevailing practice of presumptively diagnosing malaria in all cases of febrile illness in a clinic serving a refugee population on the Thai-Myanmar border METHODS: A retrospective review of 3,506 patient charts from December 1993 through June 1994 at the MaeSot medical clinic to compare clinical signs of malaria to blood smear findings. Patients presenting without fever were assumed not to have malaria; the remaining 2,111 patients presenting with fever had blood smears examined for malaria infection. RESULTS: Fever alone sufferedfrom poorpositive predictive value (54.7 percent) and specificity (59.3 percent). When fever was combined with hepatosplenomegaly and anemia, the positive predictive value and specificity improved (84.5 percent and 98.5 percent, respectively). However, this combination also resulted in an unacceptably poor sensitivity (16.5 percent) and false negative error rate (835/1,000). CONCLUSIONS. In this nonimmune refugee population, severe complications of falciparum malaria occur quickly and commonly; aggressive chemotherapy is necessary to reduce morbidity and mortality. Until laboratory facilities are made available, all cases offever should continue to be treated presumptively as malaria. PMID- 11769336 TI - Disparities in surgical treatment of early-stage non-small-cell lung cancer. AB - This study involved 1,564 black or white patients diagnosed in 1992 to 1997 with non-small-cell lung cancer, reported to the population-based Connecticut Tumor Registry, who were linked with a statewide hospital discharge database that provided information on comorbid conditions. While only 11.4 percent of patients did not receive surgical treatment (lung resection), this proportion increased with rising age and was higher among patients who resided in a census tract in the highest poverty-rate quintile, were black, not married and had one or more selected comorbid conditions. These associations persisted in logistic regression models that included all of the variables as predictors of surgery. Studies are needed to explain these disparities. PMID- 11769337 TI - Fibrin glue eliminates the need for packing after complex liver injuries. AB - Hemostasis after traumatic liver injury can be extremely difficult to obtain, particularly in coagulopathic patients who have suffered extensive liver damage. We determined the ability of a fibrin glue preparation (FG) to terminate ongoing bleeding using a new, clinically relevant porcine model of complex hepatic injury. Anesthetized swine (n = 6, 18 to 19 kg) received an external blast to the right upper abdomen and were immediately anticoagulated with intravenous heparin (200 u/kg). Uncontrolled hemorrhage from blast continued from time of injury (t = 0 minutes) to t = 15 minutes. Lactated Ringer's solution was infused to keep mean arterial pressure (MAP) > 80 mm Hg until the end of experiment (t = 90 minutes). Animals underwent routine surgical techniques to control bleeding, and FG was employed in the event these measures failed. Estimated blood loss and fluid resuscitation volume were measured. Serial MAP, arterial base excess, and temperature were recorded. Animals were severely injured with significant blood loss prior to laparotomy (26 +/- 6 cc/kg) and during routine surgical efforts to arrest hemorrhage (11 +/- 2 cc/kg). Bleeding could not be controlled with standard techniques in any animal. FG rapidly controlled hemorrhage and eliminated the need for packing. Re-bleeding was noted in only one animal (portal vein injury). FG can control severe hepatic hemorrhage when surgical techniques fail. Further work in the clinical arena is warranted to determine the potential benefits of FG in arresting hemorrhage in hemodynamically unstable coagulopathic patients with complex hepatic injuries. PMID- 11769338 TI - Music of the left hemisphere: exploring the neurobiology of absolute pitch. PMID- 11769340 TI - Treatment of pernicious anemia by a special diet. 1926. PMID- 11769339 TI - Recent strategies to overcome the hyperacute rejection in pig to human xenotransplantation. AB - Due to the ever increasing shortage of suitable human donors, alternative strategies are sought to moderate the current discrepancy between the number of executable and required transplantations. Xenotransplantation (i.e., the transplantation of organs [tissues or cells] between different species) appears to be a reasonable solution. However, various problems (immunological, physiological, infectious-microbiological, ethical-juridicial) seem to be associated with xenotransplantation. One of the most formidable barriers to xenotransplantation is the phenomenon of hyperacute rejection that may lead to the destruction of the transplanted vascularized organ in a few minutes to hours. In the pathogenesis of hyperacute rejection, xenoreactive antibodies and the complement system appear to be of primary importance. Various methods can be applied to prevent hyperacute rejection; both the recipient and the donor can be treated. In this brief review, the author attempts to present a synopsis of the possible therapeutical interventions to prevent hyperacute rejection.. PMID- 11769341 TI - Electron cryo-microscopy: the frozen frontier of structural biology. PMID- 11769342 TI - Smorgastarta and gumbo: a recipe for cross-cultural success. PMID- 11769343 TI - Physiological assessment of tongue function in dysarthria following traumatic brain injury. AB - A tongue pressure transducer system was used to assess tongue strength, endurance, fine pressure control and rate of repetitive movement in a group of 20 individuals, aged 17 to 60 years, with dysarthria following severe traumatic brain injury (TBI). Comparison of the TBI group's results against data obtained from a group of 20 age and sex matched control subjects revealed reductions in tongue endurance and rate of repetitive movement. Tongue strength and fine pressure control, however, were found not to differ significantly from the control group. Pearson's product-moment correlations indicated there to be only weak correlations between the physiological nonspeech tongue parameters and the deviant perceptual articulatory features exhibited by the TBI group. Further analysis of the results on an individual subject basis revealed no clear relationships between the physiological and perceptual parameters suggesting that the TBI subjects may have been compensating in different ways for the physiological impairments. PMID- 11769344 TI - Linguistic skills in relation to neurological findings at 8 years of age in children born preterm. AB - The linguistic skills of 8-year-old children born preterm (n = 42) with birthweight < 1750 grams from a 1-year birth cohort for 1985-86 in northern Finland were studied with three different language tests, namely the Illinois Test of Psycholinguistic Abilities (ITPA), the Token Test for Children (TTC) and the Morphological Test (MT) for Finnish children. Full-term control children (n = 42) with birthweight > or = 2500 grams from the same birth cohort were matched individually with their preterm pairs for age, sex, twinship, mother's education, place of residence, birth order and family type. The preterm children's language abilities were studied in relation to their neurological status and to the periventricular leukomalacia (PVL) findings of magnetic resonance imaging (MRI). The preterm children with minor neurodevelopmental dysfunctions (MND) scored worst and differed significantly from their matched controls in TTC. They also differed significantly from other preterm subgroups, namely healthy preterm and preterm children with cerebral palsy (CP), in verbal comprehension measured by TTC. PVL findings were not associated with performance in the language ability tests. A closer and regular follow-up of language development in the MND-disabled group among the low-birthweight preterm children is recommended. PMID- 11769345 TI - Effects of amplified and damped auditory feedback on vocal characteristics. AB - This study tested two possible methods for reducing vocal load e.g. during classroom speech. Six female subjects read aloud from a text (1) under normal circumstances, (2) while hearing their own voice amplified (through headphones) and (3) with auditory feedback damped by foam plastic earplugs inserted in the outer ear canal. Fundamental frequency (F0) and sound pressure level (SPL) decreased during both amplified and damped feedback. Additionally, during amplification the relative level of F0 compared to that of the first formant diminished, likewise the alpha ratio. These changes may indicate reduced vocal fold adduction. The results suggest that both amplification and damping of auditory feedback may reduce vocal load during phonation. PMID- 11769346 TI - Describing different styles of singing: a comparison of a female singer's voice source in "Classical", "Pop", "Jazz" and "Blues". AB - The voice is apparently used in quite different manners in different styles of singing. Some of these differences concern the voice source, which varies considerably with loudness, pitch, and mode of phonation. We attempt to describe voice source differences between Classical, Pop, Jazz and Blues styles of singing as produced in a triad melody pattern by a professional female singer in soft, middle and loud phonation. An expert panel was asked to identify these triads as examples of either Classical, Pop, Jazz or Blues. The voice source was analysed by inverse filtering. Subglottal pressure Ps, closed quotient QClosed, glottal compliance (ratio between the air volume contained in a voice pulse and Ps), and the level difference between the two lowest source spectrum partials were analysed in the styles and in four modes of phonation: breathy, flow, neutral, and pressed. The same expert panel rated the degree of pressedness in the entire material. Averages across pitch were calculated for each mode and style and related to their total range of variation in the subject. The glottogram data showed a high correlation with the ratings of pressedness. Based on these correlations a pressedness factor was computed from the glottogram data. A phonation map was constructed with the axes representing mean adduction factor and mean Ps, respectively. In this map Classical was similar to flow phonation, Pop and Jazz to neutral and flow phonation, and Blues to pressed phonation. PMID- 11769347 TI - Clinical evaluation of anaemia in sheep: early trials. AB - Trials were conducted on a farm in Mpumalanga Province in South Africa to test the possibility of grading the colour of the ocular mucous membranes of sheep as an indication of the extent to which the animals are affected by Haemonchus contortus infection. The range of observed colour shades were classified into five categories, from red, through red-pink, pink and pink-white to white. Over a period of 125 days routine drenching of a flock of 388 sheep on irrigated kikuyu (Pennisetum clandestinum) pasture was terminated. During this time the animals were examined at practically weekly intervals and haematocrit determinations done for all the sheep with pale conjunctivae. Only those sheep having a haematocrit of 15% or lower were treated. Compared to a previous drenching tempo of close to every 3 weeks during the Haemonchus season on the farm, drenching was reduced by approximately 90%, as 70% of the sheep did not require salvage drenching and only 10% of the flock had to be given more than one salvage treatment. At the time of the trial the five clinical classifications were not related to predetermined haematocrit categories. However, when compared to categories that were set in later trials, 94% of the clinical estimates in the present trial were either in the correct haematocrit category, or, if not, the sheep were probably not disadvantaged by the errors. In 2.6% of cases the incorrect estimate may have placed the sheep concerned in jeopardy, as the haematocrit values were so low that salvage drenching was required, while the sheep were not regarded as anaemic. Changes in the mean haematocrit values of drenched and undrenched sheep were mirrored reciprocally by the changes in clinical colour estimates. Lactating ewes were by far the most susceptible class of sheep, as only 44.6% of them were able to manage without drenching, compared to 83% of dry, and 70.6% of pregnant ewes. Correlations between the haematocrits and clinical estimates were highly significant, although the associations were not high enough to give reasonable surety that the haematocrit values of individual animals could be predicted with confidence from their clinical classifications. Exceptionally large numbers of worms were recovered from seven of the 14 sheep that were culled because of age at the end of the trial, but these were reflected neither in their faecal worm egg counts, nor, with one exception only, in clinical signs. PMID- 11769348 TI - Normal oral bacterial flora from some southern African snakes. AB - Eighteen snakes representing 11 species were subject to mouth swabbing on 58 occasions. Of these swabs, 52.2% were positive for bacteria. A total of 92 bacterial isolates were cultured, representing 30 species of which 81.5% were Enterobacteriaceae, 16.3% gram positive cocci, and 2.2% anaerobes. Swabs from non venomous snakes were more commonly bacteriologically sterile than those from venomous snakes (P = 0.0107). The oral bacterial flora did not differ between captive and newly captured snakes. The bacterial species found were not constant in a single snake with time, in the same snake species, the same serpentarium or geographically. The bacteria most commonly cultured were Proteus spp., Pseudomonas spp., Salmonella arizonae and Staphylococcus epidermidis. Colony counts tended to be low. Three or more bacterial species per venomous snake per occasion were more common in winter than summer (P= 0.0192). PMID- 11769349 TI - A survey of parasitic nematode infections of chickens in rural Zimbabwe. AB - A survey to determine the nematode species in rural chickens reared extensively was carried out in six districts of Zimbabwe. Two-hundred-and-seventy chickens were randomly collected from the districts and processed for helminth recovery. One genus and 10 species were identified from the gastrointestinal tract but no parasites were found in the respiratory tract and eyes. Skrjabinocerca sp., Capillaria obsignata, Capillaria contorta and Trichostrongylus tenuis are new records in Zimbabwe. Allodapa brumpti and Tetrameres americana were the most common species with a prevalence of 64.8% and 64.1%, respectively. PMID- 11769350 TI - Epidemiological observations of Zimbabwean theileriosis: disease incidence and pathogenicity in susceptible cattle during Rhipicephalus appendiculatus nymphal and adult seasonal activity. AB - Fifty-nine Hereford cattle susceptible to tick-borne diseases were used as tracer animals to assess the tick challenge and pathogenicity of Theileria parva under field conditions in Zimbabwe. They were moved periodically in groups of five to three commercial farms (one group consisted of four) during seasons of Rhipicephalus appendiculatus nymphal and adult activity. All tracer cattle were herded together with the farm cattle but were not dipped. The nymphal tick counts were high on two of the farms (up to 2000 per animal) but were very low on the third farm (less than ten per animal). On the three farms, 19 out of 24 (76%) tracers had patent Theileria schizonts. There was a range of clinical manifestations of theileriosis with acute and fatal infections occurring on one farm. The adult R. appendiculatus infestations during the wet season numbered 120 800 per animal on the three farms. The disease transmitted by the adults was very pathogenic on the three farms; 30 out of 35 (86%) had severe theileriosis infections. Cattle, which survived the nymphal diseases challenge, showed various degrees of immunity to subsequent T. parva challenge transmitted by adult ticks. Therefore, 13 out of 18 (72%) of these cattle had a second disease episode and the case fatality rate on the three farms was 46%. The factors which determined the epidemiological status of Theileria challenge on the farms, such as the farming systems and presence of wild animals, are discussed. PMID- 11769351 TI - Exposure of cattle immunized with different stocks of Theileria parva to buffalo associated Theileria challenge on two game parks in Zimbabwe. AB - Eight cattle immunized with cattle-derived Theileria parva Boleni stabilate together with six susceptible controls were released in Dombawera Game Park on the Highveld of Zimbabwe. This coincided with Rhipicephalus appendiculatus nymphal activity. The cattle grazed together with African buffaloes (Syncerus caffer) and were not treated against tick infestation. The nymphal tick infestation was high, and seven of the eight immunized cattle and three of the controls had severe and fatal reactions. Subsequently, two stocks of Theileria parva to be tested for their immunizing abilities were prepared-one from adult ticks which were fed as nymphs on one of the sick control animals (Dom 268) and the other from adult ticks collected from pastures grazed by buffaloes (Bv-1). Two groups of cattle were immunized with either the Dom 268-derived strain (eight animals) or the Bv-1-derived strain (four animals). These together with three non immunized controls, were released in Bally Vaughaun Game Park in the Highveld, where buffaloes are present, during the season of nymphal tick activity. A third group of five cattle, immunized with stabilate Bv-1, and three non-immunized controls were released at the same site during the season of adult tick activity. The nymphal and adult tick infestations of the cattle were large and more than 2000 nymphs and 1000 adult ticks were counted per animal. Cattle were treated with a pyrethroid pour-on preparation to control the tick infestation and screw worm strike. The immunized cattle in the three groups survived the theileriosis challenge for a period of 18 months, but the non-immunized control cattle suffered a severe and fatal theileriosis 19-23 days after being placed on the pasture. PMID- 11769352 TI - Laboratory and field investigations into the Theileria parva carrier-state in cattle in Zimbabwe. AB - The Theileria parva carrier-state in cattle on commercial farms on Zimbabwe was investigated using parasitological and serological methods. The proportion of cattle showing Theileria piroplasms on two farms, which had recent histories of disease outbreaks, were 64% (n = 106, total of heifers and weaned calves examined) and 71.5% (n = 60) while the proportion of T. parva antibodies for the same animals were 59% and 98.5%, respectively. On four farms where no cases of the disease occurred for over 10 years, the average proportion of animals showing piroplasms and antibodies were 55.4% (range 32-82, n = 223) and 73% (range 47-91, n = 223), respectively. However, on another three farms which had no history of theileriosis outbreaks these proportions were very low, being 11.4% (0-24, n = 157) for piroplasms and 12.2% (5-23, n = 157) for antibodies. The mean infection rate in unfed Rhipicephalus appendiculatus adults collected from farms with a high prevalence of cattle which were carriers of Theileria piroplasms during the tick activity season was 29% (range 12-60%) with 9.3 (range 2-18.7) mean infected acini per infected tick. The infectivity of different tick batches to susceptible cattle produced a wide spectrum of theileriosis reactions. Laboratory controlled experiments were carried out to study the persistence of T. parva (Boleni) piroplasms in cattle immunized with this strain as well as its infectivity for ticks and its subsequent transmissibility to cattle. Examination of the salivary glands of 15 batches of ticks collected from six immunized cattle on three different occasions over 18 months showed that none were infected with Theileria parasites. However, the infectivity of other ticks in the same batches to susceptible animals was demonstrated 6, 10 and 18 months after cattle had been immunized with Boleni stabilate. PMID- 11769353 TI - Lamproglena hoi n.sp. (Copepoda: Lernaeidae) from two yellowfish hosts, Barbus marequensis and Barbus polylepis, caught in a river in Mpumalanga, South Africa. AB - Lamproglena hoi n.sp. species was collected from the gill filaments of largescale yellowfish, Barbus marequensis A. Smith, 1841 and smallscale yellowfish, Barbus polylepis Boulenger, 1907 from the Spekboom River, Mpumalanga, South Africa. The genus Lamproglena is characterized. Morphological features of L. hoi are described and illustrated by means of drawings and scanning electron micrographs. This species is also compared with congener species described from other Barbus spp. PMID- 11769355 TI - Tuberculosis in kudus (Tragelaphus strepsiceros) in the Kruger National Park. AB - Five kudus (Tragelaphus strepsiceros), three bulls and two cows, within the Greater Kruger National Park complex, were diagnosed with generalized tuberculosis caused by Mycobacterium bovis. The lesions seen in these animals were similar to those previously reported in kudus and included severe tuberculous lymphadenitis of the nodes of the head and neck (that resulted in noticeable uni- or bilateral swelling beneath the ear), thorax, and the mesentery. All the animals also suffered from severe granulomatous pneumonia. The lesions in the lungs were more severe cranially and had a miliary distribution elsewhere in the lungs. Based on the DNA patterns of the M. bovis isolates, at least some of these kudus were infected with strains commonly present in tuberculous buffaloes, lions, cheetahs, and baboons in the Park whereas other strains from these kudus were quite different and may reflect another source of infection. The presence of tuberculous kudus in the Park is expected to complicate control measures that may be instituted to contain or eradicate the disease in the Park. PMID- 11769354 TI - Immunization of cattle against East Coast fever using Theileria parva (Marikebuni) and relaxation of tick control in North Rift, Kenya. AB - A total of 90 animals was immunized against East Coast fever (ECF) using Theileria parva (Marikebuni) stock on three large-scale farms in Kiminini Division, Trans-Nzoia District, North Rift, Kenya. Another 90 cattle served as non-immunized controls. Following immunization the number of cattle with significant indirect fluorescent antibody (IFA) titres increased from 43.9% to 84.4% and 6.7% of the cattle developed clinical ECF reactions. Two months after immunization, the immunized and non-immunized cattle were divided into two groups one of which was dipped every 3 weeks and the other dipped when total full body tick counts reached 100. All the animals were monitored for 51 weeks for incidences of ECF and other tick-borne diseases. Twenty-four cases of ECF were diagnosed among the non-immunized cattle compared to four cases among the immunized cattle; a difference that was significant (P > 0.05). There was no significant difference in the incidences of babesiosis and anaplasmosis between the immunized and non-immunized cattle. PMID- 11769356 TI - Validity of intradermal tuberculin testing for the screening of bovine tuberculosis in Madagascar. AB - A sample survey with the objective of determining the prevalence of bovine tuberculosis by means of an intradermal tuberculin test was conducted in Madagascar and it was found that the prevalence rate varied from 0-30% by veterinary district. In order to estimate the true prevalence, the validity of the test was investigated by assessing its sensitivity and specificity in two groups of animals from two different regions, which were destined for slaughter. In the first group where the probability of non-infected animals should have been the highest, sensitivity was estimated at 0.52 (n = 21) and specificity at 0.99 (n = 79). In the second group selected on the basis of apparent ill health of the animals in a high-prevalence bovine tuberculosis area, sensitivity was estimated at 0.8 (n = 10) and specificity at 1 (n = 12). The results obtained from both groups of cattle were not combined for statistical purposes because the sensitivity of the skin test seemed to fluctuate in relation to the chronicity of the disease. These fluctuations are discussed. However, since the first group of zebu cattle was more representative of the cattle population across the country as a whole, its results were retained as operational parameters for further screening. PMID- 11769357 TI - Tuberculosis, caused by Mycobacterium bovis, in a kudu (Tragelaphus strepsiceros) from a commercial game farm in the Malelane area of the Mpumalanga Province, South Africa. AB - Tuberculosis, caused by Mycobacterium bovis, was diagnosed for the first time, in a kudu cow from a commercial game ranch in the Malelane area of the Mpumalanga Province close to the Kruger National Park. This diagnosis has important implications for the eradication of the disease in commercial and communal livestock in the area. Kudus are considered to be a potential maintenance host and, because of discharging fistulae in the parotid area where the lymph nodes are commonly infected, they have the potential of disseminating bacteria over wide areas. Cognisance should be taken of the presence of tuberculosis in a species other than domesticated cattle in this area and its implications for the control of tuberculosis in cattle. PMID- 11769358 TI - ["Stress"--a problematic concept. Not only external strain results in stress related symptoms]. PMID- 11769359 TI - [Cure of hemophilia is approaching. Gene therapy is the hope]. PMID- 11769360 TI - ["Consolatory eating" is not a myth. Stress-induced increased cortisol levels result in leptin-resistant obesity]. AB - Recent studies indicate that stress induces increased food intake only when stress is followed by a neuroendocrine reaction with increased cortisol concentrations. The stress of modern society may contribute to the current epidemic of abdominal obesity, which is characterised by increases in cortisol and leptin concentrations. This is a condition which carries a great risk for cardiovascular disease, type 2 diabetes mellitus and stroke. PMID- 11769361 TI - [Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important]. AB - Hormonally related side effects of antipsychotic drugs, e.g. weight gain, hyperlipidemia and diabetes have come to the forefront in that the use of clozapine and new antipsychotics have increased. Hormones involved are prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), insulin and leptin. Patients treated with clozapine had lower levels of GH-dependent IGF-I than patients receiving classical antipsychotics. Patients treated with olanzapine had higher serum insulin levels than those receiving classical antipsychotics, indicating a probable influence of olanzapine on insulin secretion. In clozapine treated patients the insulin levels correlated to the clozapine serum concentration, indicating a likely influence also of clozapine on insulin secretion. The gender difference, i.e. that women normally have higher leptin levels than men, was found in patients receiving classical antipsychotics, but not in patients treated with clozapine or olanzapine. PMID- 11769362 TI - [Can we afford good cholesterol lowering therapy? Budgeting of statin costs versus medical needs in the county of Stockholm]. AB - Increasing drug costs are a concern in Sweden. The costs for statin treatment are considerable, and among those increasing most rapidly (by 30-35% per year). Our survey of eligibility for statin treatment in Stockholm according to current Swedish recommendations (i.e. patients < 75 years with elevated cholesterol and manifest atherosclerotic disease, hereditary dyslipidemia, and diabetes) indicates marked undertreatment. The cost for statins in Stockholm 2000 was SEK 175 M (144 M for patients < 75 years). The projected cost, if current recommendations were to be fully implemented, is SEK 450 M for the target group and > 100 M extra for patients > 75 years and/or high cardiovascular risk. We propose that individual risk assessments should replace crude patient group recommendations to obtain reasonable "numbers needed to treat", i.e. to optimize the expenditure on statins and cost-effectiveness of the therapy. Prioritization of drug expenditures (within and between patient categories) must be debated, and medical needs must be made clear to those who determine the medical budget. PMID- 11769363 TI - [Comparison of two therapeutic regimes for diabetes-stricken children. Social and mental resources of the family are often crucial for the prognosis]. AB - In a prospective, randomized intervention study, 36 children with diabetes mellitus type I were followed, the aim being to study if a family psychosocial intervention at diagnosis could improve glycemic control and minimise hospital admissions. The control group was treated initially in a hospital ward, while the whole family of the children in the study group received therapeutic and social support in an out-hospital training apartment. In the study group only, both parents reported a significant improvement of the family climate. An increased risk for poor glycemic control was recorded in children living in one-parent families and in families where the father had a low level of education. Younger age, a single-parent family and poor glycemic control were factors associated with more days of rehospitalization. The divorce rate in the whole group was at least as high as in the normal population but, surprisingly, maternal dysfunction was associated with lower levels of HbA1c. The conclusion is that the social family background is a most important factor for the glycemic control and need for hospital readmission of the diabetic child. PMID- 11769364 TI - [Doping in endurance sports. Survey of individual [Hb] levels can expose doping]. AB - Doping through increasing [Hb] increases physical performance in sport. Therefore, no cross-country skiers with [Hb] values above 160 and 175 g/l for women and men, respectively, may start in competitions. Even plasma expanders have been used, possibly for lowering a high [Hb] but this procedure may not increase physical performance. There are methods available for detecting the use of erythropoietin but not reinfusion of erythrocytes to increase [Hb]. To make it more difficult to increase [Hb] by different unethical methods we suggest that the [Hb] in endurance athletes is determined both during the training and the competition season to establish individual [Hb] mean values and range. Since endurance training at altitude does not increase [Hb] after return to sea level, an occasional increased [Hb] is suspicious. In such a case complementary doping tests may be used. PMID- 11769365 TI - [When is it meaningful to investigate hematuria? Macroscopic hematuria- investigate always. Microscopic hematuria--symptoms and age decide]. AB - All patients (n = 578) referred during one year and for whom hematuria was mentioned in the referral form were monitored following urological evaluation including urography and cystoscopy. Evaluation of macroscopic hematuria was often associated with significant findings at both urography (stones) and cystoscopy (bladder tumors). The situation was the same even if not as pronounced for evaluation of microscopic hematuria with concomitant urinary tract symptoms. The evaluation of asymptomatic microscopic hematuria was, however, very rarely associated with significant findings, which were moreover totally lacking among women and younger males. PMID- 11769366 TI - [Menorrhagia--a symptom not sufficiently surveyed. The path to diagnosis and treatment lined with ambiguity and misunderstandings]. AB - Approximately 10 percent of all women of fertile age suffer from menorrhagia, a symptom defined as regular heavy menstrual bleeding. Finding the cause of the symptoms can often be the key to effective treatment. Apart from anatomical causes such as myomas and adenomyosis which underlie less than half of all cases, recent studies have been pointing toward a hitherto unrecognized over representation of mild hemostatic disorders such as von Willebrands disease and platelet dysfunction. Efforts have been made to spread information about the problem, but as with most "new" information it has been met with some skepticism. Lately though, there have been nationwide campaigns in the USA and Canada in which targeted information and instruction is aimed at lay educators as well as health care providers, informing about these circumstances. Advantages of a correct diagnosis are not only the of to choosing more efficient treatment. When a hemostatic disorder has been diagnosed there follows a reduced risk of complications in connection with surgery, trauma and delivery. PMID- 11769367 TI - [Case reports. Sudden blue cutaneous discoloration--an alarming symptom]. PMID- 11769368 TI - [Direct-to-consumer advertising makes common symptoms a medical issue]. PMID- 11769369 TI - [Long-haul flights increase the risk of pulmonary embolism]. PMID- 11769370 TI - [A bloody exhibit in Frankfurt]. PMID- 11769371 TI - [The most common reasons of patient's wish to have medical records erased: insulting judgments; distrust when it comes to confidentiality]. PMID- 11769372 TI - [Patients with iatrogenic hepatitis C will be compensated for psychological and social suffering]. PMID- 11769373 TI - [The impossible task of primary health care? Local initiatives when it comes to resource allocation can be the solution]. PMID- 11769374 TI - [Stress-related fatigue--some therapeutic experiences]. PMID- 11769375 TI - [The weakest part of a chain...]. PMID- 11769376 TI - [Is it possible to boil away alcohol from the glogg-wine?]. PMID- 11769377 TI - [Dosage of thyroid hormone in substitution therapy]. PMID- 11769378 TI - [New licence requirements for 45-year old drivers of trucks and buses- certification provided at a health center during evening hours in Ostersund]. PMID- 11769379 TI - [Incomplete information about photographic documentation of accidents]. PMID- 11769380 TI - [Clinical predictors of left ventricular function improvement after percutaneous coronary interventions in patients with ejection fraction below 45%]. AB - BACKGROUND: The value of clinical predictors of left ventricle function recovery after surgical revascularization in patients with decreased ejection fraction is well documented. However, there are no clinical studies assessing factors which can influence left ventricle function in patients with coronary disease and low ejection fraction (LVEF) undergoing percutaneous coronary interventions (PCI). OBJECTIVE: We tried to assess clinical prognostic factors of left ventricle function improvement after PCI in patients with coronary artery disease and impaired LVEF. PATIENTS AND METHODS: We studied patients with LVEF < 45% undergoing PCI. We assessed duration and grade of symptoms of heart failure, angina class and echocardiographic parameters of LV systolic function. After 6 months follow-up LVEF was obtained again. We analyzed influence of baseline clinical factors on LVEF recovery after PCI. RESULTS: We studied 29 patients (mean age 54.4 +/- 11 years) before and after PCI. In the whole group of patients we found significant increase in EF (38.4 +/- 6% vs 50.4 +/- 15%, p = 0.005) at follow up examination. There was significant improvement of EF in patients with NYHA class I or II (from 40.4 +/- 5% to 58.1 +/- 9%, p < 0.0001) as compared to NYHA class III or IV (from 31.4% +/- 9% to 31.8 +/- 11, p = NS). In multivariate regression analysis correlation between NYHA class and LVEF at control examination (beta = -0.54, p = 0.03) was independent from epidemiological variables and baseline LVEF. There was significant increase in LVEF in patients with severe angina (CCS III or IV) as compared to patients without angina (DEF 21.3 +/- 5% vs 7.9 +/- 10%, p = 0.009). There was also higher increase in LVEF in patients with chest pain during balloon inflation (delta EF 17.4 +/- 9% vs 5.7 +/ 9%, p = 0.01). CONCLUSIONS: Mild symptoms of heart failure and independent predictors of left ventricle function recovery after PCI in patients with impaired LVEF. The lack of angina symptoms negatively influence LVEF recovery after PCI. PMID- 11769381 TI - [Intracoronary ultrasound assessment of balloon angioplasty with "stent-like' angiographic result]. AB - The aim of the study was to evaluate by intracoronary ultrasound (ICUS) the efficacy of optimal coronary balloon angioplasty (POBA) guided by quantitative coronary angiography (QCA). The study population included 40 patients who underwent conventional coronary balloon angioplasty, in whom a stent-like result was achieved (percent diameter stenosis (%DS) < 35% in QCA). In all patients diagnostic ICUS assessment was performed after the procedure. The site of stenosis and the proximal and distal reference segments were analysed with respect to residual plaque burden (RPB), true vessel dimension (the media-to media diameter) and type of vascular remodelling. Despite an optimal angiographic result residual plaque burden was 70 +/- 6% at the site of stenosis, whereas in the reference segments it was around 45% indicating the severity of atherosclerosis in angiographically normal vascular segments. No significant differences were seen between averaged reference vessel diameter in QCA (Ref.D) and averaged luminal reference diameter in ICUS. In contrast, true vessel diameter in ICUS was significantly larger than Ref.D in QCA (p < 0.001). Positive vascular remodelling at the site of stenosis was observed in most patients. Optimal angiographic result of QCA-guided POBA does not indicate optimal dilatation of the lesion. In most patients ICUS reveals marked residual plaque burden, which is an independent predictor of restenosis after percutaneous coronary interventions. PMID- 11769382 TI - [Attempt of estimation of Q fever endocarditis frequency in Poland]. AB - Up to now no Q fever endocarditis (caused by rickettsia Coxiella burnetii) has been diagnosed in Poland. Potential endocarditis caused by Coxiella burnetii strains can be related to a group of strains present in Poland or sensitivity of Polish Population. The aim of the study was to estimate frequency of Q fever endocarditis is patients of National Institute of Cardiology and to characterize Coxiella burnetii strains and correlation between frequency of Q fever endocarditis and the group of strains. In all patients infective endocarditis and valvular heart disease were diagnosed. In all cases vegetations on TTE or TEE and negative blood cultures were confirmed. No fungal antigens or elevated anti Candida and anti-Aspergillus antibodies were found. Serological investigations as far as it concerns C. burnetii antibodies were negative in all cases. No Coxiella burnetii infection were found in patients with infective endocarditis and negative blood cultures in the National Institute of Cardiology. However due to high probability of occurrence of such an infection in Poland further investigations in other centers would be useful. PMID- 11769383 TI - [Blood pressure variability on the basis of 24-hour ambulatory blood pressure monitoring in a group of healthy persons]. AB - The aim of our research was to test twenty four hour variabilities of blood pressure (BPV) in a group of healty persons. The group consisted of 125 healthy persons (58 men and 67 women) 14-70 years old (mean age 33.8 +/- 14 years). Standard deviation (SD) from average blood pressure and the presence and size of night fall of arterial blood pressure (dippers and non dippers) was tested as parameters of BPLV. Average twenty four hours systolic blood pressure (SBP) in all the group was 119.7 +/- 10.9 mm Hg (123.5 +/- 11.5 mm Hg during the day and 106.2 +/- 12.2 at night). Average twenty-four-hour diastolic blood pressure (DBP) in all group was 71.9 +/- 9.0 mm Hg (74.0 +/- 9.5 during the day, 62.8 +/- 9.3 mm Hg at night). The mean SD of 24-hour SBP was 15.2 +/- 3.5 mm Hg (13.6 +/- for day's hours and 11.2 +/- 4.1 mm Hg at night). The mean SD of 24-hour DBP was 13.0 +/- 2.6 mm Hg (12.1 +/- 2.8 at the day and 9.8 +/- 3.0 at night). There were no correlation between and SBP SD or DBP SD and sex, age of the investigated patients and their membership to dipper and nondipper group. The positive correlation between SBP and and its SD was observed in the group with SBP below 120 mmHg and the same was ascertained in group of people below 40 years of life. Average night fall of SBP was 17.17 +/- 9.42 mm Hg (13.9 +/- 7.4%). Average night fall of DBP was 11.70 +/- 6.91 mmHg (15.7 +/- 8.8%) Nondippers ascertained 28.8% of all group. (32.8% of women and 24.4% of men). Multivariate analysis showed relationship between membership to dipper group and mean diurnal systolic blood pressure (odds ratio 0.93, 95% confidence interval 0.89-0.97, p = 0.02) and between low value of systolic pressure SD during all day monitoring and mean diurnal systolic blood pressure (odds ratio 0.94, 95% confidence interval 0.89 0.99, p = 0.02). Variability of arterial blood pressure is sex, age and mean diurnal pressure related. Parameters of short and long term variability are characterised by large repeatability. Our variability values can be voice in discussion on the norms in analysis of normal blood pressure patients. PMID- 11769384 TI - [Effect of severe multiple trauma complicated by acute lung injury on endothelial cell activity]. AB - The pulmonary endothelium synthesizes many bioactive compounds and their activation or injury may cause release these substances into the blood. We determined the influence of trauma severity for endothelium activation/injury by measurement of specific endothelial cell markers--soluble E-selectin (sES) and von Willebrand factor antigen (vWF:Ag). Thirty six severely traumatized patients were stratified according to an Injury Severity Score (ISS). Group I--patients with ISS > or = 35, Group II--patients with ISS < 35. Eleven healthy volunteers served as controls. Serum sES and plasma vWF:Ag concentrations were measured and PaO2/FiO2 ratio, Lung Injury Score (LIS) and APACHE II ratio were calculated at the admission to IC, after 24 h and on 2, 3, 5, 7, 10th day. In all investigated time periods, we observed significant increase in serum sES concentration among patients from group I, in comparison to initial value and control. On day 3, serum sES concentration was significantly increased in group I, in comparison to group II. In the first seven days, plasma vWF:Ag concentration in patients with severe multiple trauma (ISS > or = 35) was significantly elevated, in comparison to group II and control. At the admission, significant correlation between plasma vWF:Ag and ISS was found (Rs = 0.568, p < 0.001). Significant correlation between plasma vWF:Ag and serum sES concentration was also observed (Rs = 0.501, p < 0.001). In conclusion, severe trauma patients manifest endothelial cell activation/injury. Plasma vWF:Ag concentration seems to be an important, early marker of trauma severity, while serum sE-selectin level may serve as prognostic factor in immediate postinjury period course. PMID- 11769385 TI - [Factors influencing prevalence and clinical course of cytomegalovirus (CMV) infection in kidney transplant patients]. AB - In the paper the authors tried to identify factors influencing prevalence and clinical course of cytomegalovirus (CMV) infection in kidney transplant patients. The study was performed in the group of 100 patients after cadaveric kidney transplant followed up in the Chair and Department of Nephrology, Collegium Medicum, Jagiellonian University in Krakow. CMV infection was demonstrated to occur more frequently and significantly earlier in the patients administered prednisone, cyclosporin A and mycophenolate mofetil, compared to the group treated with standard triple-drug-therapy (prednisone, cyclosporin A, azathioprine) or double-drug-therapy (prednisone, cyclosporin A). Higher serum levels of cyclosporin A did not increase prevalence of the infection but urged its onset. Risk for CMV infection was however higher in the group of patients treated for acute rejection episodes, especially with antilymphocyte preparations. No differences were shown in the immunological matching within HLA A, -B and -DR antigens between the patients without features of CMV Infection and those treated for its active form. The infection occurred significantly more frequently in the recipients with HLA-A1 antigen than in those with HLA-A9 and DR7. In patients with delayed transplanted kidney functioning, time of the infection onset and a number of its episodes were similar to the remaining population, however severity of the clinical course positively correlated with the duration of acute tubular necrosis (ATN). CMV infection occurred slightly more frequently in patients requiring transfusions compared to those not administered blood preparations. Among patients with AB blood type, active CMV infection occurred statistically less frequently, whereas in those with other blood types percentage of patients with/without CMV infection were comparable. PMID- 11769386 TI - [Bone complications in diabetic subjects with good metabolic control and without any long-term complications--certain problems. Part III: The influence of hypertension and type 2 diabetes mellitus co-incidence of calcium, phosphorus and magnesium metabolism]. AB - Both high morbidity and potentiation of systemic complications emphasise significance of diabetes mellitus and hypertension co-incidence. The aim of the study was to analyse the influence of hypertension accompanied with type 2 diabetes mellitus on calcium phosphorus and magnesium metabolism. The study was performed in standard low-calcium diet conditions on the group of 49 patients with type 2 diabetes mellitus (among them 27 had hypertension), 14 patients with essential hypertension and 20 healthy persons. Both serum and urine concentration of creatinine, calcium, phosphorus, hydroxyproline, hydroxylysine and uric acid were analysed. Oral calcium load test was done. Serum alkaline phosphatase activity and oxalic acid urine excretion were also estimated. There were no significant differences between diabetic patients with and without hypertension as far as calcium, phosphorus or magnesium metabolism were concerned. PMID- 11769387 TI - [Insulin effect on metabolism in skeletal muscles and the role of muscles in regulation of glucose homeostasis]. AB - Insulin enhances glucose disposal, storage and oxidation in muscles. It control the metabolites required in the muscle and is involved in maintaining glucose homeostasis. Insulin is considered to be an anabolic hormone in that it promotes the synthesis of protein and glycogen and it inhibits the degradation of these compounds in muscle tissue. Glucose normally provides energy sources for tissues of the body, its uptake by muscle requires a secretion of insulin. The initial step of glucose utilization requires the transport of glucose into the cells. The transport across certain cell membranes such as muscle is regulated by insulin. The insulin-receptor complex stimulates the cellular uptake of glucose. Insulin stimulates the uptake of amino acids into cells and simulates protein synthesis in muscle tissue. With insulin deficiency, amino acids are mobilized from muscle and transported to the liver. Physiological increase in insulin suppresses lypolysis in skeletal muscle but in supra-physiological increases this suppression of intramuscular lypolysis is inadequate, resulting in increased availability of nonestrified fatty acids which can represent a potential mechanism involved in insulin resistance in muscle. Patients with diabetes mellitus are characterized by insulin deficiency (type 1) or peripheral insulin resistance (type 2) demonstrated by decreased insulin action on glucose utilization in muscle. Muscle tissue has been considered to be a major regulator of systemic glucose homeostasis. PMID- 11769388 TI - [The role of beta 3-adrenergic receptors in the human organism]. AB - Beta 3-adrenergic receptors (beta 3 ARs) are important structures in the human body but the role they play is not yet very clear. Stimulation of beta 3 AR in adipose tissue causes greater energy expenditure and increases thermogenesis and lipolysis. Mutation of the gene coding beta 3 AR in position 64 with thymidine instead of cytosine leads to the replacement of tryptophan (Trp 64) with arginine (Arg 64) and may be the cause of greater increase in body mass and the decrease in basic metabolism. The data however, is differentiated in populations and cannot be conclusive. The connection has been discovered between the state of the beta 3 ARs and the blood lipid concentration (also differing in populations). In some patients beta 3 AR mutation is correlated with high arterial diastolic pressure, increased incidence of noninsulin-dependent diabetes in younger, increased insulin resistance and diabetes in pregnant. beta 3-AR agonists might be used in treatment of many diseases, which obviously demands further investigations. PMID- 11769389 TI - [Percutaneous closure of atrial septal defect]. AB - Present state of knowledge about dynamically developing procedure of percutaneous atrial septal defect closure has been collected on the basis of the contemporary literature review. History of the method has been presented and a brief characteristics of implants used nowadays has been made with emphasis on their advantages and disadvantages. Technique and possible complications of the procedure have been described. Indications and contraindications to this way of treatment have been quoted. Comparison of percutaneous and surgical treatment has been made with indication of benefits following the less invasive character of percutaneous treatment. PMID- 11769390 TI - [Use of Cyclosporine A and new immunosuppressive drugs in the therapy of glomerulonephritis]. AB - Multiple clinical trials have been undertaken during last years to assess indications, efficiency and safety of glomerulonephritis treatment with new immunosuppressive drugs as cyclosporine (CsA, Mycophenolate Mophetil (MMF) and Tacrolimus (FK 506). The main indication for cyclosporine is nephrotic syndrome resistance to steroids and cytotoxic agents, steroid-dependent and multi relapsing cases with serious toxic side effects or with contraindications for steroids and cytotoxic drugs. CsA was administered at the dose of 4-5 mg/kg/day in adults and 5-6 mg/kg/day in children. The best results were achieved with minimal change disease. The durable remission occurred in 70-80% of cases of steroid-sensitive nephrotic syndrome and in 20-30% of steroid-resistant forms. There was a lower rate of remission and a high risk of cyclosporine nephrotoxicity in other types of glomerulonephritis. Therefore CsA, MMF and FK506 remain a late therapeutic option for patients with these types of glomerulonephritis and severe clinical course. As the long-term CsA therapy may be complicated by acceleration of renal fibrosis, a renal biopsy is mandatory before its administration. PMID- 11769391 TI - [Changes in ovaries after hysterectomy]. AB - Although simple hysterectomy is one of the most frequent gynecological operations, there is still the lack of clear criterions to the procedure with macroscopic unchanged ovaries in perimenopausal term. The aim of study was to examine setting changes in ovaries after hysterectomy. The study included 40 women aged between 40 and 49 years, who underwent hysterectomy due to myoma, leaving their bilateral changes in ovaries connected with age two study groups were distinguished, the first group included 21 patients aged 40-44 years and the second one--19 patients aged 45-49 years. The occurring of pathological changes in remaining ovaries and changes in ovaries function were estimated. The period of observation lasted two years. The function of ovaries was observed by estimation of FSH and of E2 and of total volume of ovaries before operations and after 6, 12, 24 months following hysterectomy. The results of observation were compared with similar marks of female patients with intact uterus and were exactly in the same age group. Pathological changes of uterine appendages as ovary cyst that needed a repeat operation was in 1 patient-(2.5%) The fundamental statistical differences in level of FSH and of E2, volume of ovaries between examined and controlled groups were not important. Also the trends in changes of the level of these parameters taking place during the observation in both study groups were not statistically significant. On the basis of the examinations it can be stated that the hysterectomy in the group of women at the age 40-49- doesn't have an influence on function of remaining ovaries. The decision how to treat the ovaries in case of hysterectomy should take into consideration the results of an interview and individual patient's preferences. PMID- 11769392 TI - [Thyroid carcinoma--contemporary diagnostic principles and treatment]. AB - Thyroid cancer, which is a rare neoplasm, is still controversial issue. References approved in Poland in 1995 caused unification of the extension of thyroid surgery to total resection of thyroid gland in case of cancer. For many surgeons such a radical treatment is still doubtful. On the other hand thyroid cancer is an object of many studies because of its heterogenous clinical course and prognosis depending of histological type. This article focuses on modern principles of diagnosis, treatment and follow-up according to obligatory references in Poland. The authors show current epidemiological data, prognosis according to histological type of cancer and explain pathogenesis of the disease. Preoperative diagnostic model has been described including role of ultrasound examination, biopsy, cytology and histology examination. Special interest was taken to follow-up patients after total thyroidectomy emphasising the role of thyreglobin in early detection of cancer recurrence. It is also important to observed patients for the rest of their life because cancer recurrences have been reported even 40 years after surgery. Preoperative diagnosis and treatment is a typical example of multi-disciplinary procedure which should be held in specialistic centres with proper equipment and experience. PMID- 11769393 TI - [Histocompatibility HLA system in man. Considerations in the light of current concept. Part III. The relationship between HLA antigens and disease susceptibility]. AB - A large number of diverse diseases are associated with genetic markers of the MHC complex. The analysis of such disease associations is complicated by the diversity of genetic information located within the HLA complex. Recent advances in the structural analysis of HLA genes and gene products contribute a new perspective to questions of HLA-associated disease. HLA-associated disease are caused by an interplay of many different genes and environmental factors, where HLA complex genes most often confer the strongest genetic predisposition. With this knowledge at hand, identification of individuals at high risk to develop autoimmune and other potentially disabling diseases should be used in order to effectively prevent or halt disease development. This may be a major part of the clinical HLA field in the near future. In this article, we present and interpret some such recent information, especially a possible molecular mechanism of the HLA associations. PMID- 11769394 TI - [Urological complications in patient after kidney transplantation. Correction of ureter stenosis with consequent proper renal graft function]. AB - Urological complications constitute significant problem following renal transplantation. Incidence ranges from 4 to 14% in graft recipients. The most important aspects concerning these complications are early diagnosis and prompt treatment, any delay in diagnosis and management may lead to deterioration of renal graft function or graft loss. The following case report discusses management of hydronephrosis in renal graft caused by ureter stenosis due to scarring and fibrosis of its distal end after remote kidney transplantation. The patient was a 33-year-old woman with previous history of end stage renal failure in the course of chronic glomerulonephritis. A triple drug immunosuppressive regimen consisting of Azathioprine (AZT), Cyclosporine A and Encorton (AZT + CsA + Encorton) was administered during a period of three years after kidney transplantation. At this time AZT administration was discontinued due to chronic viral hepatitis type B. Episodes of expansion sensation (discomfort) and graft pain were reported by the patient which after 3 days were followed by a period of oliguria and then anuria. The patient was admitted to the Department of Nephrology CMUJ, where ultrasound imaging revealed graft hydronephrosis. In the presence of such clinical and biochemical indications due to acute graft failure, one hemodialysis session, was performed. The patient was transferred to the Urological Department CMUJ where ureter exploration was attempted, but was unsuccessful. Subsequently percutaneous nephrostomy was performed which lead to immediate diuresis. Next, distal ureter stenosis (located by the urinary bladder) was surgically removed and reimplantation of the ureter was carried out. Due to early diagnosis and surgical reconstruction of the transplanted ureter, renal graft function returned to normal requiring only one hemo-dialysis session. PMID- 11769395 TI - [Surgeons in Krakow between WWI and WWII]. AB - During the war time when Polish borders had not been established yet, apart from having two surgical departments Jagiellonian University, Krakow had surgical departments in the Bonifratow, Izraelicki and Military Hospitals. More surgical departments were opened up in later years in pubic Health System Hospitals, among them were Narutowicz at near Pradnicka street and Sisters of Mercy at Lea street. Other well-known Krakow surgeons operated in smaller, private surgeries, such as: Dom Zdrowia (House of Health) or Zwiazkowy (Union) Clinic. At that time only 30 Surgeons worked in Krakow. They were outstanding specialists with a broad practice. Among them were Maksymilian Rutkowski, Jan Glatzel, Stanislaw Nowicki, Michal Hladij. Gradually, younger surgeons started to join them. they were: Jan Kowalczyk, Jerzy Jasienski, Stanislaw Kania, Wladyslaw Laszczak, Jozef Bugusz, Jozef Gasinski. Many of them who worked in the surgical hospitals in Krakow, left the city after obtaining a professorship (like Kornel Michejda, professor at the University of Wilno) or became heads of wards, like Zygmunt Drobniewicz, Alfons Mackowski and Tadeusz Guschlbauer. All of these surgeons were highly respected by the medical community as well as by the general public in their respective town and surrounding areas. A large income allowed that best of them to fund and supply their own wards. Occasionally, however, among the less successful surgeons, an uncompromising competition for patients developed. These events were disapproved and condemned by the medical establishment. Many surgeons led an active life outside of their profession. A surgeon with an exceptionally colorful personality was Jan Glatzel: witty, highly intelligent, a connoisseur of fine art, book lover with an active social life. Maksymilian Rutkowski was active in charitable organizations, helping to support Bratnia Pomoc Medykow. Michal Hladij, president of KS Cracovia, vice president of Krakowski Klub Automobilowy rendered his service to restore monumental cauldron in Rdzawka on the hillside of Obidowa. Others, like Dr Jozef Friszer, a former assistant in the Surgical Hospital, who also came from Krakow, later became and influential politician and the last prime Minister of the Second People's Republic. PMID- 11769396 TI - The history of the Chair and Department of Pathological Anatomy at the Jagiellonian University and School of Medicine in Krakow on the 150th anniversary of its foundation. PMID- 11769397 TI - Human carcinogenesis, the new genetics, and the practicing pathologist. PMID- 11769398 TI - E-cadherin, beta-catenin and stromelysin-3 expression in de novo carcinoma of the colorectum. AB - An apparent exception to the colorectal adenoma-carcinoma carcinogenic pathway is the so-called "de novo" carcinoma that has no evidence of adenoma in its vicinity. Despite the fact that they are often quite small, these lesions appear to bhe more aggressive (i.e. have greater likelihood of lymph node metastases) than carcinomas that clearly arise from surrounding adenomas ("ex-adenoma carcinoma"). The purpose of the present immunohistochemical study was to compare rates of cell adhesion molecule (E-cadherin and beta-catenin) and protease (stromelysin-3 (ST-3)) expression in groups of de novo (n = 64) and ex-adenoma (n = 42) lesions in order to see if their more aggressive behavior is associated with decreased cell adhesion and increased protease expression. Although beta catenin expression showed abnormalities (decreased or nuclear expression), it did not differ between the two groups. In contrast, the rates of extensive ST-3 expression and decreased E-cadherin expression were significantly higher in de novo group (P = 0.014 and 0.005, respectively). Histopathologically the de novo group had a significantly higher percentage of case with an infiltrative invasion pattern. These differences highlight the more aggressive phenotype of the de novo colorectal cancer and fit with a greater invasive potential of it. PMID- 11769399 TI - Fhit protein expression in hereditary and sporadic colorectal cancers. AB - The majority of hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in DNA mismatch repair genes, especially in MLH1 and MSH2. Tumours in such patients also show microsatellite instability characteristic for DNA repair defects. The FHIT gene, a candidate tumour suppressor gene located at 3p14.2 has been shown to be involved in carcinogenesis of many human tissues, including digestive tract tissues. In our study, we characterized Fhit protein expression in hereditary and sporadic colorectal cancers (CRC). Our intention was to determine if cancers with mutations in the mismatch repair genes, MSH2 and MLH1, would show more frequent inactivation of the FHIT gene. Sixteen HNPCC and 28 sporadic CRC cases were examined by standard immunohistochemical analyses. Both study groups comprised carefully and selectively chosen cases. We have observed higher frequency of loss or reduction of Fhit protein expression in hereditary CRC than in sporadic cases (44% vs. 25%). Although this difference was not statistically significant (p = 0.17), possibly due to the small number of available tumour specimens, the tendency is interesting. More extensive studies on a larger number of cases should be done in the HNPCC group to confirm statistical significance. Our results suggest that the FHIT gene plays an important role in carcinogenesis of at least one fourth of all colorectal cancers. PMID- 11769400 TI - Glomus tumour of the oesophagus. AB - The authors describe a unique case of glomus tumour (glomangioma) located in the oesophagus in a 79-year-old woman. PMID- 11769401 TI - Metastases to the products of conception from a maternal bronchial carcinoma. A case report and review of literature. AB - The association of mother's malignancy with metastases to the products of conception is rarely reported. We present 8th case reported in the literature of oat-cell lung carcinoma complicated by an aggressive clinical course and documented placental metastases. Review of all published cases of lung cancer metastasizing to the placenta is also presented. A 44-year-old white pregnant woman at an estimated gestational age of 30 weeks presented with cervical incompetence symptoms and multiple tumors of 2-4 cm in diameter located in the subcutaneous tissue of the chest, including both breasts. The biopsy revealed a metastatic oat-cell carcinoma. Cesarean section was performed immediately. During the procedure, micronodular metastatic infiltration of the liver was noted. Microscopic examination of placenta showed clusters of oat-cell carcinoma calls within the intervillous spaces; no infiltration of villi themselves was noted. The malignant cells were morphologically identical as those of the subcutaneous metastases. The woman succumbed to cancer and died on the 16th postoperative day. Lung cancer metastasizing to the placenta is relatively rarely reported. In all cases only placental metastases were found; the fetus in all cases was spared. Only in one out of 8 reported cases outcome of mother was not fatal. It should be emphasized that not in all cases of maternal malignancy the histological examination of the placental was made Therefore it is possible that the incidence of placental involvement is more often than it is reported. PMID- 11769402 TI - How much information can physicians actually assimilate? PMID- 11769403 TI - Rudolph H. Kampmeier, MD--personal recollections. PMID- 11769404 TI - Linking data from the 2000 Tennessee Youth Tobacco Survey to program action. PMID- 11769405 TI - The criminalization of adults with mental illness (part 2). PMID- 11769406 TI - December depression: holidays blues may be intensified by terrorist fears. PMID- 11769407 TI - Loss prevention case of the month. Frequent complication overlooked. PMID- 11769408 TI - Ten things you should know when being sued. PMID- 11769409 TI - Brain oxidative stress in the syndrome of mutual aggravation on the model of combined injury in Mongolian gerbils. AB - General reaction of an organism (survival, body temperature, hematocrit, glycemia) was followed in Mongolian gerbils subjected to isolated head injury (brain ischemia--LD5), to peripheral injury (ischemia of both hind limbs--LD20), and to combined injury (head injury + peripheral injury). In the early period (1 hour) after the injury, parameters of oxidative stress were followed in the brain cortex (superoxide anion, index of lipid peroxidation, activity of superoxide dismutase and glutathione reductase). Obtained results indicate that the combined peripheral and central injury of low lethality leads to the worsening of general response of the organism with high lethality of experimental animals (LD80). Likewise, the increased cortical production of superoxide anion and index of lipid peroxidation, as well as the disturbances of antioxidative enzymes activity suggest on an important role of brain oxidative stress in the development of the syndrome of mutual aggravation in animals subjected to combined injury. PMID- 11769410 TI - [Outcome of kidney transplantation in patients on peritoneal dialysis]. AB - The initial experience suggested that kidney transplantation could be hazardous for patients on peritoneal dialysis due to the high risk of peritonitis and a possible high incidence of acute rejection. In this paper we have presented our experience with kidney transplantation in these patients. During the last four years kidney transplantation was performed in 9 patients on peritoneal dialysis. The average time spent on peritoneal dialysis was 20.6 +/- 7.6 months. In all patients peritoneal catheter was removed during the surgery. During the posttransplantation period a triple immunosuppressive therapy including steroids, cyclosporin and azathioprineor mycophenolate mofetil was administered in all patients. In comparison to patients on hemodialysis no significant difference in the incidence of acute rejection episodes, delayed graft function, graft arterial thrombosis and graft function recovery was observed. Patients on peritoneal dialysis had significantly greater and longer wound drainage in comparison to patients on hemodialysis. It was concluded that peritoneal dialysis had no negative influence on short-term outcome of kidney transplantation. PMID- 11769411 TI - [Computerized tomography of the thorax in evaluation of resectability of pulmonary carcinoma]. AB - A group of 49 patients with non-small cell lung carcinoma was investigated at the Clinic of Pulmonary Diseases of the Military Medical Academy in the period 01.01.1995.-01.03.1999. In all patients were performed bronchoscopy, ultrasound of the abdomen and computed tomography (CT) of the thorax. The patients suspected to have locoregionally disseminated disease were selected. The aim of the investigation was to estimate the reliability of CT of the thorax in the evaluation of the possibility for lung carcinoma resection. The findings were confirmed either by invasive diagnostic procedures and/or during thoracotomy. During the evaluation of the direct invasion of mediastinal organs, sensitivity of the method was 48% and specificity was 89%. In the evaluation of the mediastinal lymph node metastases by CT scan, sensitivity of the method was 68.4% and specificity was 81.3%. Reliability of CT of the mediastinum was significantly higher in the detection of lymph nodes suspected to be metastatically altered than in the evaluation of the direct carcinoma invasion into mediastinal organs. PMID- 11769412 TI - [The closed head injury syndrome--frequency and character of brain parenchyma lesions]. AB - The aim of this investigation was to determine the frequency and character of the brain parenchyma lesions using CT scan and MR in patients with closed head injury, and afterwards to establish the connection of those changes with clinical parameters (neurological deficit and the degree of consciousness disorder), evaluating the sensitivity and specificity of neuroradiological procedures. The investigation comprised 40 patients with closed head injury. Grade of neurological deficit (Canadian Neurological Scale) and the degree of consciousness disorder (Glasgow Coma Scale) were determined in all patients by the same neurologist. The results revealed significantly higher specificity and sensitivity of brain examination using MR in patients with closed head injury, particularly in the detection of small ischemic and contusion lesions. Likewise, the correlation of positive findings using MR was more significant concerning the grade of neurological deficit and the degree of consciousness disorder compared to the brain examination using CT scan. PMID- 11769413 TI - [Systemic manifestations of idiopathic inflammatory myopathies--part two]. AB - The aim of the investigation was to establish if the finding of immunoserologic and pathohistologic parameters of the altered humoral immune response in patients with dermatopolymyositis was associated with the occurrence of more severe clinical patterns of the diseases followed by general symptoms and the affection of visceral organs. Sensitivity, specificity, accuracy, positive and negative prediction of immunologic parameters of the disease were determined compared to the occurrence of certain systemic manifestations of the disease. Significant (80 100%) correlation of systemic manifestations with the altered immunoserologic and histopathologic parameters of the disease was confirmed, so that it could be assumed that pathologic humoral response had a significant role in the onset of systemic manifestations during dermatopolymyositis. Predictive value of indicators was of the utmost importance. If the increased values of immune complexes, vasculitis in the muscle and the other cited indicators of the altered humoral response were confirmed in a patient, more severe course of the disease could be expected, which was of practical value for the planning of therapeutic approach, estimation of the disease course and its prognosis. PMID- 11769414 TI - [Clinical study of administration of abciximab--a monoclonal antibody to platelet glycoprotein IIb/IIIa in percutaneous intracoronary interventions]. AB - During the last 10 years a new group of drugs was developed--platelet glycoprotein IIb/IIIa blockers that is nowadays largely and efficiently used as for the prevention of percutaneous coronary intervention complications as well as in the treatment of acute coronary syndromes. In the period February-June 2000- 19 patients (18 males, 1 female, of average age 53.3 years) were administered Abciximab in the bolus dose of 10 mg immediately before the intervention and afterwards 10 mg by 12-hour infusion. All patients received aspirin and ticlopidine hydrochloride if the stent was introduced and heparin by the standard protocol. Elective intervention was done in 17 patients (non-Q infarction in 3 patients, unstable angina pectoris in 5 patients, postinfarction angina pectoris in 2 patients, acute myocardial infarction at least 1 month before the intervention in 6 patients and 1 patient with myocardiopathy) and in 2 patients the intervention was performed during the myocardial infarction. In 15 patients (79%) intracoronary stent was introduced and in 5 patients (21%) the intervention was performed on 2 arteries. Maximal immediate effect of the dilatation was achieved in 18 patients (94.7%). In the first 60 days of the follow-up 1 patient (5%) died of some other disease, and in no patients symptomatic myocardial ischemia was found. No adverse effects were observed. PMID- 11769415 TI - [The masticatory efficiency test in evaluation of the functional value of Rehm rebased newly made total dental prostheses]. AB - The aim of the study was to determine the functional value of unrebased, rebased by Rehm and new complete dentures and compare the time of initial functional adaptation of patients to rebased and new complete dentures. The study included 72 subjects. The functional value of complete dentures was estimated by the test of masticatory muscles bioelectrical activity, by the test of masticatory efficiency and by the test of maximal physiological load. On the basis of the study it was concluded that the complete dentures rebased by Rehm were worthier in function than the unrebased ones, and the period of initial functional adaptation was missing. In the subjects with a pair of newly made complete dentures, functional tests revealed the reduction of the initial values after the new dentures were delivered. During the examination interval progressive dynamics with the tendency of establishing the optimal functional value and the initial functional adaptation was observed after 21 days. PMID- 11769416 TI - [Detection of B-lymphocyte clonality in samples of salivary gland tissue in patients with primary Sjogren syndrome]. AB - Intensive lymphoplasmocytic infiltration with atrophy of glandular tissue structures is the dominant patohistological feature found in exocrine glands of patients with Sjogren syndrome (SS). The infiltrates consist of T and B lymphocyte clusters that make the structures resembling germinal centers, and numerous plasmocytes that are secreting imunoglobulines locally, including autoantibodies. By applying the polymerase chain reaction (PCR) in our study we have shown the existence of dominant B cell clone in salivary glands samples of 4 out of 6 patients with SS, in the absence of clinical, routine laboratory, and patohistological signs of the lymphoma. B lymphocyte clones were detected upon the amplification of gene segment that encoded variable heavy chain immunoglobulin CDR3 region. Finding of single, dominant B lymphocyte clone could be of predictive significance, because these patients are predisposed to non Hodgkin lymphoma (NHL) for which there is an assumption that it originates out of salivary glands from one of the clusters of proliferating B lymphocytes. PMID- 11769417 TI - [Mesothelial cysts and cystic mesothelioma of the greater omentum and peritoneum: comparative analysis]. PMID- 11769418 TI - [Current methods in the diagnosis of deep venous thrombosis]. PMID- 11769419 TI - [Recommendations for early detection, prevention and treatment of osteoporosis]. PMID- 11769420 TI - [Adequacy of peritoneal dialysis]. PMID- 11769422 TI - [Detection of K-ras and p-53 oncogene mutations in a patient with acute lymphoblastic leukemia before and after bone marrow transplantation]. AB - We present a case of 22 years old male patient, who was submitted to singenic transplantation of hematopoietic cells originating from the bone marrow in the remission phase of the diagnosed acute lymphoblastic leukemia (ALL). The bone marrow sample was donated by his healthy twin brother. The pretransplantation and transplantation phases were regular. We analyzed the presence of K-ras and p-53 point mutations in our patient with ALL and for the first time we had the opportunity to analyze the samples from two monozygotic twins. DNA was isolated from the peripheral blood mononuclear cells (PBMNC) by the standard procedure, of the patient with ALL before and after bone marrow (BM) transplantation and of his clinically healthy twin brother. Samples were subjected to PCR amplification of K ras exons 1 and 2 and p-53 exons 5, 6, 7 and 8. In PBMNC of the patient with ALL before BM transplantation, mutations were observed in exon 1 of K-ras and exon 8 of p-53 gene. These mutations were found neither in PBMNC sample of his twin brother, nor in PBMNC of the patient with ALL after BM transplantation. In the p 53 exons 5, 6 and 7 and exon 2 of K-ras, there were no mutations in any analyzed samples. Detected mutations in K-ras and p-53 genes could be a part of larger genetic abnormalities and the obtained results had shown the possibility of using DNA mutational changes in the follow-up of the success of BM transplantation. The molecular disease marker that was found by this method was also significant for the detection of minimal residual disease at the molecular level. PMID- 11769421 TI - [Rhino-orbital zygomycosis]. AB - Zygomycosis is rare but highly invasive fungal infection, with high mortality rate. A 67 years old diabetic man was presented with rhino-ocular form of the disease. Fungal elements invaded the skin and subutaneous facial tissue, with involvement of the nose, paranasal sinuses and orbit. The portal of entry of fungus was through paranasal sinuses, after the tooth extraction. Various clinical manifestations were presented: headache, facial swelling, tenderness over the involved sinuses, unilateral orbital cellulitis with proptosis, facial and orbital pain, black nasal discharge, decreased visual acuity, blindness. Patient was treated surgically and by liposomal amphotericin B. He underwent maxillectomy, ethmoidectomy and sphenoidectomy and orbital exenteration because of the dissemination of the disease into the orbit. The specific diagnosis of the infection was established upon the microscopic demonstration of casual agent in the debridement tissue. Early diagnosis was important in this highly fatal disease. Aggressive surgical debridement, therapy with amphotericin B and correction of underlying metabolic acidosis must be performed. The successful medical therapy in this patient suggests that lipid formulation of amphotericin B should be given, because this antifungal agent performed the best control of the infection with the minimal adverse effects. PMID- 11769423 TI - [Diffuse and binodular goiter in a patient with tuberous sclerosis]. AB - Tuberous sclerosis complex is hereditary multisystemic, neurocutaneous disorder characterized by hamartomatous lesions mainly involving the brain, skin and viscera. Thyroid gland is rarely affected in these patients. Case history of a patient with tuberous sclerosis complex and diffuse and binodular goiter was presented. No epileptic seizures occurred despite multiple intracranial calcifications, cortical and subependimal tubers, revealed by neuroimaging. Borderline intellectual functioning was determined. Ultrasonographic findings of the heart, abdomen and pelvis were normal. Bone radiographs revealed multiple cystic lesions of the metacarpal, metatarsal and terminal phalanges. Clinical, endocrine and metabolic evaluations were performed because of anxiety, mild weight loss, transient problems of swallowing and breathing complaints, developing when she was 39 years old. Palpable diffuse and asymmetric thyroid enlargement was found. Laboratory tests of thyroid function, ultrasonographic examination and scintiscanning of the thyroid gland and patohistological analysis of fine-needle aspiration biopsy revealed the euthyroid, inactive, diffuse and binodular goiter. Unusual association of goiter and tuberous sclerosis was discussed. PMID- 11769424 TI - [Alcoholism and drug addiction in Bosnia-Herzegovina]. PMID- 11769425 TI - [Comments on drug abuse in Bosnia-Herzegovina]. PMID- 11769426 TI - The network of Centres for the Prevention and Treatment of Drug Addiction in the Republic of Slovenia. AB - The methadone maintenance program is one of the fundamental treatment and harm reduction programs in current drug policy that aims to protect the users of illegal drugs by increasing the number of users who make contact with the medical service and go on to join higher threshold therapy programs. National guidelines for management of drug addicts including methadone maintenance treatment were adopted by the Health Council at the Ministry of Health in 1994 and methadone maintenance program policies were confirmed. Fourteen regional Centers for the Prevention and Treatment of Drug Addictions have been established from 1995, and the professional staff working at the Centers have received additional training. PMID- 11769427 TI - [Marital therapy at the day care hospital department for alcoholism and other drug addictions at the Sarajevo Canton]. AB - Therapy of married couples in one segment of the therapeutical programs applied in Zavod za alkoholizam i druge toksikomanije in Sarajevo with the goal of protection of mental health of addicts and treatment of addictive tendencies of alcoholics. Therapeutic program is focused on marital relations. The improvement of communication between marital partners positively reflects on entire family, and better quality relations are created in the entire family environment. PMID- 11769428 TI - [Treatment of alcoholics at a day care hospital]. AB - The daily hospital (further in text D.H.) in the allcomprehensive program of the protection of the mental health has the multidimensional activity in the performing of the program of the primary, secondary and tertiary prevention. Its work is based on the principles of the ecko-psychiatry and is concepted so at the trias of the aethiologic factors: personality with its weaknesses milieux with its pressures alcohol as toxin The therapy is being performed by the complex sociotherapeutic procedures (individual, group, therapic community) and medicaments. The daily program is structured, and is performed by the multidisciplinary team. The program of the rehabilitation and the resocialisation are being led at the club of the treated alcoholics, where is included the whole family, as well as by the monitoring in the catamnestic surgery of all the treated by means of the Daily hospital. Nowadays is the Daily hospital encircled wholeness which has the possibility of the beginning and the finishing of the therapeutic programs and represents an important factor in the all comprehensive protection of the mental health. PMID- 11769429 TI - [Treatment of alcoholism in the United States of America]. AB - In this work shortly is considering the representation of the abuse of alcohol in USA, the immediate system for the treatment of the alcoholism, then, the requires for the future changes for what we believe that they will happen in the system of the treatment, as in some more important directions of the scientific researches which have influence on the clinicians. PMID- 11769430 TI - [Comprehensive approach in treatment at the day care hospital department for alcoholism and other drug addictions in the Sarajevo Canton]. AB - In this paper, experiences in treatment of alcoholics with the symptoms of posttraumatic stress disorder are presented in the form of case review. During the five year post-war period /1996-2001/ 72.8% of total number of treated patients were treated for the first time, and 34.5% had the diagnosis of posttraumatic stress disorder beside the diagnosis of alcohol addiction. In the observed period, changes in symptoms of the patients-alcoholics that were caused by the war trauma were noticed. The authors present their own experiences in the application of new techniques and the approach to these patients that have been integrated in the overall treatment system. Principles such as active treatment and multidisciplinary team approach through networked group and individual treatment forms were pointed through this case review. PMID- 11769431 TI - [A model of addiction prevention]. AB - The motive for the realization of the program prevention of the dependence on at primary school, is the knowledge that in our country last years the mental health of children and young endangered also the war which always represents the factor of high risk for psychic development and health. The experiences show that without collaboration between the different experts who are treating with the children and the adolescents has no efficacious prevention, protection, and treatment of dependence on. The better knowing of the normal psychic development leads to better knowing of the disorders and increases the successfulness of the intervention. In this paper is demonstrated the model of the program of the prevention of the dependances applied at the primary school "Edhem Mulabdich". The realization of this program ran through two phases: I-"educator education" for the teachers of the class and subject teaching and II-training program for the selected group of the teachers carriers of the preventive activities. This program we concipated so that through the structurized activities realize the following tasks: education from the different fields of the relevant for the problem of dependency, the development of the skills of the recognition of the pupils for the use of the means of dependensies: The animiting of the school environment so that the problem of dependency on the adequate manner would build in into the regular school activities the development of the expert net and institutions which will intervene in the definite cases. The application of this model for the prevention program of dependency pointed to the possibilities of the efficacious acting at school conditions, with the obligation that in the efficacious acting in school condition, with the obligation that in during the continued application the permanent gets tested, complete and adapt appropriately the requests of the community and scientific knowledges. PMID- 11769432 TI - [Legalization of drugs--pro and con]. AB - This article deals with various opinions and assertions regarding drug legalization. Societal and clinical implication regarding the effect of decrease or increase in the use of psyhoactive substances, on public health, violence and criminal activities have been pointed out. The relation between legal and illegal drugs has been considered. Special attention has been paid to arguments on legalization and decriminalization of marihuana and possible consequences on the risk group-children and adolescents. Experiences from USA and some European countries have been presented. Having in mind the specific situation in BiH, the author of article gives her own view and suggest the introduction of harm reduction strategy into BiH drug policy, without changing the legal drug status. PMID- 11769433 TI - [The Institute for Alcoholism and Other Drug Addictions at the Sarajevo Canton from its founding until today]. AB - Health protection, and especially mental health protection in Bosnia and Herzegovina have very long tradition. A first record found on treatments of mental patients originates from 13th century. Use of alcohol is old as man kind, and in the culture of nations in Bosnia and Herzegovina is present tradition of "Common" drinking, which means that drinking is a part of everyday life, more in the rural than in urban environments. Debut of organize treatment of alcohol addictors in our country is situated in the early sixties. Since that, and until the aggression on Bosnia and Herzegovina in 1992, Institute for alcoholism and substance abuse, has passed trough different developmental phases in organizational, as well in professional sense, with the trend of continuous performance improvement. This institution was unique in Bosnia and Herzegovina, and part of system consisted of organized psychiatric services. During one year average number of services was around 5,000 and 1,500 persons went trough complex social and psychiatric treatment with rehabilitation. PMID- 11769434 TI - [Nicotine addiction]. AB - According to the WHO reports from 1997, Bosnia and Herzegovina takes a disgraceful first place in smoking prevalence in Europe. 53% of smokers over 15, then 22% of women, 67% of men are percentages that are not achieved by countries at a much lower development level than B&H. The mortality rate of men (aged 35 64) as a result of tobacco varies from 11% to 45% from country to country. In 11 European countries it is > or = 40% and they are all in the eastern part of the region: Belarus, the Czech Republic, Hungary, Kazakhstan, Lithuania, Poland, Russia, Slovenia, Ukraine, B&H. Tobacco addiction, like other drug addictions, is basically a neurobiological mediated brain disease. In the same way, the discontinuation of drug taking, in this case nicotine, is a very important addiction component and one of its clearest manifestations. So, the symptoms of iving up smoking are in fact the symptoms mediated by noradrenalien (excitement, tension, long-lasting desire, distraction, insomnia, increase in appetite, putting on weight, etc). According to the Diagnostic and Statistical Manual for Mental Disorders-4th Edition (DSM-IV), both toxicomanic nicotine addiction and the discontinuation of smoking are classified as diseases. The smokers who give up smoking before they are 50 decrease their mortality risk by 50% over the next 15 years compared to those who continue smoking. This risk decrease is related to the incidence decrease and mortality rate from specific, smoking-related diseases, including: coronary heart disease, strokes, peripheral vascular diseases, COPD and lung cancer. The assistance to addict to give up of smoking is duty of professionals. PMID- 11769435 TI - [Education in family medicine--a new approach]. AB - The subject of the family medicine on the medical faculties in Bosnia and Herzegovina existed from recently as a separate curiculum of the medical study. Until recently the contents of this discipline interpreted within the subject of the social medicine or the object of the primary healthcare protection, and programs of teaching were based mainly on Anglosaxon experiences. The fact is that some teachers of the medical faculty in Sarajevo had their own visions and programs of the family medicine which by years were tested in the units of the family healthcare protection in Sarajevo, Mostar, and Banja Luka, about what was published in our and foreign literature. New approach from the family medicine should be based on as follows: greater use of the standardized procedures for the improvement of the communication skills; revised educational procedure of all the participants 6 interdisciplinaryilly in the education of the family medicine; improvement of knowledge about methodlogy and the principles of the research; improvement of the techniques and knowledge about the maipulatin of the medical informations; development of the skills of the continued studying through the total working aga; to the development of the capability of the critical estimation of the own work important; by the defining of the important educational goals in the curriculum of the urgent medicine; to the development and use of the methods feed-back informations from the students; to the modernizing of the methods of the evaluation of the educational process-adopted knowledge and the attitudes and the carrying out of the practice of the patients, and the ethic values in that process. In this work the authors consider the stated experiences in the education from the subject family medicine at our faculties realting to the foreign, and suggest that new concept of the education on the basis of these experiences in the practice. PMID- 11769436 TI - [Development of the health service for treatment and prevention of alcoholism in Bosnia-Herzegovina]. AB - In this paper author analyzed and described development and improvement of health service for prevention and treatment of alcoholism of population in Bosnia and Herzegovina. PMID- 11769437 TI - [Pathography and biography of the Empress Maria Theresa]. AB - The empress and queen Maria Theresa Habsburg-Lorraine (May 13th, 1917-November 29th, 1780) bore sixteen children in the marriage with the emperor Franz I Stepha and was famous as "mother-in-law of Europe". Her brother Leopold died immediately after he was born, her sister Amalia died in the cradle and Maria Ana died of perinatal complications at the birth of a dead infant in 1744. The famous hereditary facial dysmorphia of the "Hasburg jawe" wasn't noticed in Maria Theresa's surviving children. In October of 1738, after giving birth to her daughter Ana, a manual lysis of the placenta was performed due to the retained placenta and postpartal bleeding. In 1741 her daughter Carolina died, and in 1767 her daughter Josepha died of small pox. Her daughter Elizabeth remained deformed by the pock marks, and Maria Christina got a puerperal sepsis, but surprisingly, didn't die. Maria Antoinette ended under a guillotine in France, along with her husband Luis XVI. Maria Theresa's father, Karl VI died of the cholecystopankreatitis and peritonitis, and her husband and co-ruler most probably died of acute coronary incident in August 18th, 1765. After her husband's death she started suffering from depression with steady necrophile obsessions. Maria Theresa suffered from a chronical obstructional pulmonary disease (asthma), rehumatic syndromes, hypertension and anxiodepressive syndromes. In 1767 she had small pox. In November 11th 1780 she caught a cold which grew into a pneumonia with high fever. She died of cardiopulmonal dedompensation preceded by pneumonia and asthma. PMID- 11769438 TI - On the occasion of the First congress of nephrologists of Bosnia and Herzegovina. PMID- 11769439 TI - [PI-3 kinase/AKT/PKB signal transduction pathway in kidneys mediates angiotensin II-induced hypertension]. AB - INTRODUCTION: The activation of PI-3 kinase/AKT/PKB signal transduction pathway has implicated in the cell growth regulation and proliferation. AIM: To determine a role of PI-3 kinase/AKT/PKB signal transduction pathway in the kidney of Angiotensin II-induced hypertensive rats. METHODS: NZW (New Zealand White) rats have been infused by Angiotensin II using osmotic minipump for six days (n = 8). Control group was untreated rats (n = 6). PI-3 inase and AKT/PKB activities were measured in the presence or absence of different inhibitors. RESULTS: Angiotensin II elevated mean arterial blood pressure (MABP) to 182 +/- 2 mm Hg (p < 0.001) vs untreated control rats (95 +/- 3 mm Hg). Ras-GTPase and PI-3 Kinase activities were elevated in angiotensin II-treated group. Ras inhibitors FPT III and BMS/191563 attenuated MABP to 122 +/- 2 and 127 +/- 4 mm Hg (p < 0.05) and abolished Ras-GTPase and PI-3 Kinase activities. AKT/PKB activity followed the PI 3 kinase activity. CONCLUSION: PI-3 kinase/AKT/PKB signal transduction pathway in the kidney is activated and mediates Angiotesin II-induced hypertension. PMID- 11769440 TI - [Relation between certain parameters of renal function and prognosis in multiple myeloma]. AB - BACKGROUND: Renal involvement is one of the most common manifestations of MM, with different pathogenetic mechanisms, like overproduction of monoclonal light chains and hypercalcemia, those are commonest precipitating factors for renal failure which occurs in nearly 25% of myeloma patients. Some renal pathology is noted in over half. METHODS: We studied retrospectively 16 patients with MM treated at Nephrology and Haemathology Clinic in Sarajevo, in the period from 1996-1999 y (10 females and 6 males). All fulfilled criteria for MM diagnosis: 1. Bone marrow involvement by greater than 20% plasma cells 2. Monoclonal paraprotein in the serum and/or urine 3. Lytic bone lesions. RESULTS: Appearance of high creatinine plasma level, red and white blood cells in urine, and proteinuria are the signs of renal function reduction. Renal failure was noted in 10/16, erythbruria 6/16, pyuria, 7/16 hyperuricemia in 8/16 and 3/16 (19%) were died during hemodialysis programme, and Bence-Jones protein was noted in urine with 7/16 (43%). Severe renal failure with 5/16 was noted and beside high plasma creatinine we found high plasma calcium and Bence Jones in urine. CONCLUSION: High plasma levels of creatinine and calcium and Bence-Jones in urine, are poor prognostic signs of MM. PMID- 11769441 TI - [Significance of serum creatinine levels in respiratory insufficiency conditions]. AB - Analyses of creatinema in the cases of global respiratory failure was performed in this paper. The patients with global respiratory failure treated in General Hospital in TeSanj have been followed. For all patients laboratory analyses have been performed on the admimtion and in the time of clinical status improvement, including creatinin level, K, Na, Hb, Htc, and blood gas analyses with mesurement of pO2 pCO2 pH, BE, saturation of the blood with oxgen, BE and HCO3-. Creatinine level have been considered in coleration of body mass index, and general nutritional status. The dinamic source of creatinine level in the blood have been followed, in relation of parameters of respiratory status. The statistical significance in relation of creatinine level with the respiratory status was registrated. With the improvement of respiratory status and laboratory analyses related to respiratory status, decrease of creatinin level was registrated. Because of that the therapy given to the patients with respiratory failure could influence on potassium level, the relation of creatinnemia and potassium level in the blood wasn't considered. The high creatinin level couldn't be explained with the initial renal failure, but as the sign of metbolic adaptation to hypoxemic and hypoxyc situation on the body. The registration of high creatinine level in the situations of global respiratory failure could be the guidelines for the choice of the antibiotics for these patients, mostly for potentially nephrotoxic antibiotics, like aminoglicosides, and theirs combinations. The decision and evaluation of benefit and toxicity of antibiotics for these situations could be easier. PMID- 11769442 TI - Optimising dose in peritoneal dialysis (PD). AB - PD dose is one determinant factor for PD adequacy. With the standard CAPD prescription of 4 x 2 L per day large patients especially after residual renal function has been lost, are at risk of being underdialysed according to the current standards. By using automated PD dialysis dose can be enhanced by individualising prescription and most of even large and anuric patients can be maintained on PD. PMID- 11769443 TI - Treatment of children in the U.S. with end-stage renal disease (ESRD). AB - USA 10,434 children with End State Renal Disease or chronic renal insufficiency have been followed by NAPRTCS. 5958 renal transplants have been performed. Haemoidalysis preceeded Tx in 28%, PD in 47% and 24% were preemptive transplants. The most common diagnoses were obstructive uropathy, renal dysplasia, FSGN, reflux nephropathy and CGN. 20.4 were < 5 and 24.9% < 12 years or age a transplant. 57.7% had living related donors. The most common therapy is with prednisone, cyclosporine and mycophenalate mofetile. Time to 1st rejection episode is 755 days in LRD and 98 days in CD. 5 year patient survival is 93.5% and 5 year graft survival in LRD is 80% and in CD is 65%. 75 cases of PTLD have been reported. 3748 patients have had maintenance dialysis. Peritoneal dialysis was the main modality in 67% and hemodialysis in 39%. 0.86 episodes/year of peritonitis has occurred in PD patients. 94% of patients received EPO therapy and 15% received growth hormone therapy. 3 year patient survival on dialysis is 86.5% (69.5% in those < 1 to 92.4% in those > 12 yrs of age). 3863 patients with chronic renal insufficiency have been followed. Mean height by standard deviation score is -1.41 with one third -1.88. Growth hormone for one year increased SDS by -0.30. PMID- 11769444 TI - [Structure of chronic dialysis patients in Bosnia-Herzegovina--a multicenter study]. AB - INTRODUCTION: In BiH there are no summary data about chronic dialysis patients (CDP). With this study we tray to make first step to establish B&H system for collecting necessary data. METHODS: This is a retrospective study for 1999 years. We collect data with question form which have been distributed to dialysis centers (DC) in BiH. RESULTS: We got answer from 6 (37.5%) DC: Tuzla, Sarajevo, Bihac, Odzak, Travnik and Tesanj. Totally number of CDP was 533, 256 female (48%) and 277 male (52%), and 79% of them are between 26-65 yrs. Leading primary renal diseases were: glomerulonephritis 22%, pyelonephritis 16%, endemic nephropathy 11%, unknown ESRD 10%, polycystic renal disease 9% and diabetes 9%. Peritoneal dialysis have ben performed in 10 patients only, and bicarbonat HD in 46% of CDP. Half of the patients had serum haemoglobin lower than 7 mmol/1 and only 12% received erythropoietin. 17% of the patients had coronary disease, and 7% peripheral vascular disease. We registered 43 (8%) HBsAg, but 294 (55%) antiHCV positive patients. 52% of the CDP have been vaccinated against B hepatitis. Last year died 76 patients (14.26%), mostly caused by coronary diseases (21%), cardial failure (20%), cerebrovascular accidents (15%) and sepsis (11%). 53% of patients are on dialysis between 1-5 yrs. CONCLUSION: In this study participated 6 DC only, but we think that data we collect are good basis for establishing B&H system for registration and follow-up of the ESRD patients. PMID- 11769445 TI - [New patients with end-stage renal disease on chronic dialysis]. AB - INTRODUCTION: The aim of this study was to analyse outcome of new ESRD patients on haemodialysis. METHODS: We analysed nember, demographic data, renal disease and mortality of new ESRD patients on haemodialysis (HD) in 16-months period. RESULTS: We dialysed for the first time 74 patents with ESRD, 37 female (50%) and 37 male, average age 55.55 +/- 13.57 yrs. There were 3 patients younger than 30 yrs, 51 between 31-65 and 20 were older than 65 yrs. 29.73% of these patients were from Tuzla. Distribution of patients according to primary renal disease was: glomerulonephritis 20.77%, pyelonephrtis 14.86%, diabetes mellitus 13.86%, 29.74% others and 20.77% unknown. 11 patents (14.86%) were on HD less than 10 days, 11 patents (14.86%) were on HD less than 3 months, 35 patients (47.30%) were on HD less than 12 months, and 17 patients (22.98%) were on HD more than 12 months. 46 patients (62.16%) are still on HD, 18 (24.32%) died, 3 (4.05%) temporary stopped with HD treatments, 3 transplanted, for 3 there are no data, and 1 patient (1.35%) transferred in other center. Causes of death were as follows: unknown in 5 (27.78%), gynaecology carcinoma in 3 (16.67%), sepsis in 3 (16.67%), cardiovascular disease in (11.11%), cerebrovascular accident in 2 (11.11%), and others in 3 (4.05%) patients. In the group of died patients were 13 women (72.22%) and 5 men, average age 56.94? 13.09 yrs (28-61). CONCLUSION: Leading primary renal diseases was glomerulonephitis, pyelonephritis and diabetes. Significant percent of new ESRD patients on HD die very early, and 77% of the patients live on HD less tan 12 months. PMID- 11769446 TI - [Cadaveric kidney transplantation in patients over 60 years of age]. AB - By technological progress, changing reason and acceptance of patients to dialysis, number of older patients was significantly increased. The first transplantation of patient older than 60 years made in Rijeka 1981. From 1972 to 31.12.1999, it was performed 342 cadaveric kidney transplantation at our center. The first transplantation on patients older than 60 was performed 1981. Since then, 35 patients older than 60, have undergone the transplantation. The average patients, age was 64.9 (60-72). The most often cause of chronic renal failure was phyelonephritis (28.6% of patients) and glomerulonephritis (20%). 85.6% of patients who undergone transplantation lived longer then one year. Out of total number of the patients, 14 died with functioning transplant. The most often causes of death were cardiovascular and malign illnesses. Four patients started with haemodialysis again. Twelve patients have functioning transplant. We have no documentation about 5 patients since they lift to continue their treatments at other foreign centers. In preparation of patients for transplantation, we must take care about cardiovascular diseases. Loosing of renal grapfht due to rejection is rare. According to our experience cadaveric transplantation on patient who are older then 60, was successful method treatment. PMID- 11769447 TI - [Dose and adequacy of hemodialysis measured by the urea reduction ratio (URR and Kt/V)]. AB - BACKGROUND: There are little reports about prescribed and delivered dose of haemodialysis (HD) in B&H. If we want to reduce acute and chronic HD complications and to improve whole result of patients treatment, it is necessary to routinely monitoring and measurement of delivered dose of HD. Prescribed and delivered dose of HD have to be equal or near equal. METHODS: Blood samples were taken after the long interval in a thrice-weekly regimen before and 10 min after ultrafiltration, using Slow Flow/Stop Pumping. We measured delivered and prescribed dose of HD by URR and Kt/V, and efficacy of HD by QE. The results were processing by computerized urea kinetic modelling program. RESULTS: The mean URR was 64.69%. Mean prescribed Kt/V was 1.25 +/- 0.16 and delivered 1.23 +/- 0.14, and QE 0.99 +/- 15. Delivered Kt/V and QE were positively associated (p < 0.001). QE was significantly associated with post HD urea, and sex, but not with treatment time. CONCLUSIONS: We suggest that Kt/V can serve as an important parameter in the dose of HD, and QE as a measure of dialysis "efficacy" in a single treatment of an individual patient. PMID- 11769448 TI - [Flow obstruction and infection associated with the two-lumen subclavian catheter]. AB - INTRODUCTION: The aim of this study was estimate correlation between catheter clotting and catheter-related injection in haemodialysis (HD) patients with temporary double lumen catheters (TDLC). METHODS: We analysed 128 TDLC where we had exact microbiological result from catheter tip. There were 107 patients, mean age 54.70 +/- 15.02 years (15.80); 52 (48.60%) male ad 55 (51.40%) female, which were on haemodialysis 1162.62 +/- 183,424 (6-7200) days. RESULTS: Major reasons for application TDLC were acute HD in 56 (43.75%), a function of A-V fistula in 40 (31.25%) patients, and a function of previous TDLC in 32 (25%) patients. The primary causes of chronic renal disease were diabetes mellitus in 34 (27%), pyelonephritis in 31 (24%), glomerulonephritis in 24 (19%), polycistic kidney disease in 14 (11%), nephropathia endemic in 10 (8%) and others disease in 15 (12%) of patients. The analysed TDLC remained in place for an average of 51.34 +/ 64.03 (range 2-518) days. In case of 92 (71.88%) we got positive microbiological result (Staphylococcus coagulasa negative 33%, Staphylococcus aureus 16%, Bacillus species 9%). In 38 of these catheters (41.30%) we diagnosed problems with blood flow. Totally, we had 50 TDLC with obstruction, but in 12 of them we did not have microbiological confirmation of infection. CONCLUSION: Catheter clotting is one of the important factors that increase risk for developing catheter-related infection. PMID- 11769449 TI - [Disorders of diastolic function in patients on hemodialysis]. AB - INTRODUCTION: Impaired cardiac function is frequently present in patients on maintenance haemodialysis. AIM: To assess the left ventricular diastolic function in patients on haemodialysis. MATERIAL AND METHODS: We used 2D and pulsed wave Doppler echocardiography to evaluate the left ventricular diastolic function in 40 patients on haemodialysis and compared those to healthy controls. RESULTS: Majority of Doppler parameters were changed in patients on haemodialysis. Diastolic dysfunction was present in 77.5% patients. In comparison to the healthy controls haemodialysis patients showed significant increase in peak velocity of late diastolic filling, (A wave, 76.82 +/- 23.76 cm/s vs. 58.46 +/- 9.65 cm/s p < 0.001) and reduction in the E/A ratio (1.00 +/- 0.26 vs. 1.26 +/- 0.31 p < 0.001). CONCLUSION: There was significant impairment in left ventricular diastolic function in patients on haemodialysis. PMID- 11769450 TI - [Changes in lymphocyte receptors and their activation markers during hemodialysis using various membranes]. AB - BACKGROUND: It's known that uremia is accompanying with different alteration of immune system. Also, different type of dialysis membranes can affect the immunological competence cells--lymphocytes and their function during hemodialysis (HD). AIM OF STUDY: To establish the effect of single hemodialysis session with polysulfonic and cellulose--acetat membranes on lymphocyte subpopulations and their activation markers. METHODS: In two groups of seven patients with end stage of renal disease (ESRD) on periodic HD we were investigated flow-cytometrical expression the following markers using monoclonal antibodies (BECTON DICKENSON): CD3 (T-Ly), CD19 (B-Ly), CD4 (T helper/inducer), CD8 (T-suppressor/cytotoxic), CD4/CD8 ratio, CD16 (NK cells), CD3/HLA-DR (late activated T-cells), CD4/CD 25 (IL-2R early activated T4), CD4/HLA-DR (late activated T8), CD8/CD25 (early activated T8), CD8/CD71 (late activated CD8). Blood samples were taken before HD, 30 minutes into HD and at the end of a four hours HD session. RESULTS: Demostrates statistical increased expression T helper cells on both membranes on minute 30 from beginning of HD procedure, but more on cellulose-acetat membranes and the significant falls to normal value at the end of HD: start 46.7% minute 30: 54.9%, minute 240: 42.7%. Significant changes were in expression of NK cells on cellulose-acetat membranes: start 12.7%; minute 30: 6.0; minute 240: 11.1%. No changes were noted in activations of T Ly, T4 and T8 on the both membranes. CONCLUSION: No significant difference was found in expression of lymphocyte subpopulations and their activations during HD with polysulfone membranes. Significant changes of the expression of NK cells during HD with cellulose acetat, indicated that NK cells can be sensitive marker for biocompatibility of HD membranes. PMID- 11769451 TI - [Efficiency of high-flow dialyzers in removal of beta-2-microglobulin]. AB - BACKGROUND: [corrected] Beta-2-microglobulin (beta 2M) is protein with a molecular weight of 11.800 Daltons. A 30-fold or greater increase is found in patients(pts) over 10 years (ys) on haemodialysis (HD). The main aim of study is to evaluate high-flux (HF) dialyzer efficacy on beta 2M removal. METHODS: A sample of 15 pts was selected, 9 males and 6 females, aged 45.7 ys (31.60), mean duration on HD 156,3 months. All pts were dialyzed by standard bicarbonate HD. We used 2 type of HF membrane: cellulose diacetate (CDA) and polysulphone (PS). A blood sample for beta 2M was drown before HD, 20 minute after start of HD (for clearance beta 2M) and after HD. RESULTS: Average plasma beta 2M concentration was 53.15 mg/L (27-fold increase than normal values). Post/pre beta 2M ratio was 0.73 with clearance of 23.1 +/- 8.9 ml/min (QB = 250 ml/min, QD = 600 ml/min) for CDA dialyzers, and post/pre beta 2M ratio 0.51 with clearance of 31.9 +/- 4.5 ml/min(QB = 250 ml/min, QD = 600 ml/min) for PS dialyzer, respectively. The CDA membrane was able to remove 103 +/- 29 mg of beta 2M during a 4-hours HD session, and PS membrane 139 +/- 5,1 mg, respectively. CONCLUSION: The only HF membranes are efficient on beta 2M removal. PMID- 11769452 TI - [The vertigo syndrome, magnetic resonance and magnetic angiography of the head in patients on a chronic hemodialysis program]. AB - BACKGROUND: Vertiginous syndrome appears in more then 100 diseases, therefore subject of intensive investigation. Insufficient research has been done on vertiginous syndrome in patients on chronic program of haemodialisis. The aim of this study is to search anatomical and structural changes on blood vessels of the brain by neuroimaging techniques, as well as increased circulatory resistance on TCD, in patients on chronic program of haemodialysis. METHODS: The research has been done on 30 patients with vertiginous syndrome, 22 males and 8 females, average age 45.9 years, average duration of haemodialysis 5.83 +/- 4.5. In all patients relevant diagnostic procedures had been done (EEG, TCD, audio vestibulogram, X-ray of cervical spine), and in 14 patients with increased circulatory resistance TCD we have done MRI and MRA of the brain. Pathological EEG has been found in 10%, 40% of the patients have had normal EEG finding, while 50% had slowing (non-specific disfunction) in EEG record. RESULTS: MRI and MRA had been done in 14 patients of average age 51.21 +/- 10.82. In 13 patients we had a pathological finding of MRI and MRA, while in one patient only we had normal finding of MRA, and another one patient with normal MRI scan. In 64.2% of the sample we have had cortical cerebral atrophy, in 57.1% cortical atrophy of cerebellum, while in 35.8% apart from the mentioned changes atrophy of cerebellar vermis had been found. In 71.4% of all patients cerebrovascular disease (stroke) could be identified. Atherosclerosis changes in blood vessels of anterior or posterior circulatory segment were found in 78.5% of the patients, while spasm of arteries had been registered in 21.4% of the sample. CONCLUSION: MRI and MRA of the brain brought light on aethiological aspect of vertigo in these patients. Results of our research indicate vascular aethiology of vertiginous syndrome in patients on chronic program of haemodialysis. PMID- 11769453 TI - [Bicarbonate versus acetate hemodialysis: effects on the acid-base status]. AB - BACKGROUND: Metabolic acidosis is an inevitable complication of chronic renal failure and one the major goals of haemodialysis (HD) treatment is correction of acidosis. The main aim of study was to compare effects of bicarbonate versus (vs) acetate HD on acid-base. METHODS: A sample of 36 patients (pts) was done, 20 males and 16 females, aged 52.4 +/- 12.7 years, duration on HD 46.8 +/- 40.2 months, 15 pts on acetate and 21 pts on bicarbonate HD. We determined the parameters of acid-base before and after HD, electrolyte status, Kt/V and URR. RESULTS: At start of HD: pH-7.33 +/- 0.04; pCO2-4.95 +/- 0.5 kPa; HCO3 19.1 +/- 1.9 mmol/L on bicarbonate HD vs. pH-7.33 +/- 0.03; pCO2-4.81 +/- 0.4kPa; HCO3(-) 18.7 +/- 2.0 mmol/L on acetate HD. At the end of session: pH-7.45 +/- 0.02; pCO2 5.07 +/- 0.4 kPa; HCO3(-)-26.3 +/- 1.5 mmol/L on bicarbonate HD vs. pH-7.43 +/- 0.03; pCO2-4.55 +/- 0.3 kPa; HCO3(-)-22.6 +/- 1.8 mmol/L on acetate HD. CONCLUSION: Bicarbonate as a physiological buffer is much efficient in correction of metabolic acidosis and should be preferred in HD treatment. PMID- 11769454 TI - [A high prevalence of hepatitis C in hemodialysis]. AB - BACKGROUND: Dialysis patients are among groups at risk for development of Hepatitis C infection. Most studies show a significant correlation between anti HCV seropositivity and the number of blood transfusions and duration of dialysis. Transmission of HCV by transfusions has become rare since the introduction of antibody screening. However nosocomial transmission of HCV within dialysis units increase. The aim of the study was to evaluate the prevalence and the incidence of seroconversion for HCV in our HD unit during the period from January 1997 to 2000. METHODS: We studied 133 pts (59 females) mean age 50.2 + 14 with mean dialysis duration of 35 months, from the beginning of 1997 to January 2000. 71 pts were seronegative and 62 seropositive for anti-HCV antibodies. The seroprevalence of confirmed anti-HCV patients increased from 46.51% (1997 yrs) to 49.06% (1998) and dropped in 1999 (46.62%). RESULTS: The yearly seroconversion rate ranged from 11.52% (1998) to 7.52% (1999). Till the end of 1998 all patients shared same machines, and from 1999 we had 3 separate machines for only negative patients. Our results showed that duration of dialysis is risk factor for development HCV infection (p < 0.01) seropositive 5.215 + 3.9 years, seronegative 2.2 + 1.55, as also multiple blood transfusions > 5 units. CONCLUSIONS: Our results confirmed previous investigations that duration of HD and blood products are risk factor for HCV infection. High incidence seropositivity by our patients suggested nosocomial transmission of HCV, and was needed implementation of universal precautions in HD units. PMID- 11769455 TI - [Characteristics of the early posttransplantation period in kidney transplantation]. AB - INTRODUCTION: Renal transplantation has become the procedure of choice and the most cost-effective strategy for the management of patients with end stage renal disease. Posttransplant period is very important because possible complications, which have to be detected and treated according to approve statements. The aim this paper with is to show all characteristics of early postransplant period in patients operated at the Clinical Center of Tuzla. METHODS AND RESULTS: Eighteen patients with end stage renal diseases has been analyzed with average age 32 + 8.6 years. Glomerulonephritis as primary kidney diseases has been found in 16 patients, lupus nephritis and reflux nephropathy in one patient. We paid attention on: creatinine level, urine output and balance, level of cyclosporin, body weight, ultrasound fallow-up, number episodes of acute rejection and number of additional dialysis. Clinical and labs sign of acute rejection have been found in 6 patients. Two of them recidive pulse dose of corticosteroides and four ATG. Additional haemodialysis has been performed in 5 patients. One patient died because of the rupture aneurism of aorta. Other 17 patients have been discharged after average hospitalisation of 20.87 8.18 days. CONCLUSION: We can say it's very important to recognise the sings of acute rejection and to start with therapy. In patients with cardiovascular risk, postoperative period has to be guided careful. PMID- 11769456 TI - [Review of immunosuppressive drugs in organ transplantation]. AB - In transplantation method, efforts should be made to prevent the patient immunological reaction against the transplantation antigen. In the same time, the patient general immunological reactivity must be kept. With the increasing need for transplantation the interest for new immunosuppressive drugs has become greater. The use of immunosuppressive drugs have dated since early 1950 (azatioprin and steroids). 1960 there was the appearance of the polyclonal ALG/ATG. In 1970 the true advance has been the discovery of the first selective immunosuppressive-cyclosporin (second generation). The third generation of immunosuppressive drugs with high specific place of action, has become available now (tacrolimus, thymoglobulin, zenepax, rapamune). The purpose of this paper was to show the different groups of immunosuppressive drugs, taking into account a different place of effects and different mechanisms of their immunosuppressive action. The aim of the immunosuppressive drugs combination is to achieve the optimal immunosuppression with minimal side-effects. PMID- 11769457 TI - [Occurrence of bacteriuria in malignant hematologic diseases]. AB - BACKGROUND: Infection risk with patients suffering from hematological malignant diseases is a result of an interaction between a patient and a host and of a dysfunction of organs. During the evolution, human beings have developed an effective defense mechanism. It was defined with functioning of: 1) skin and mucus membranes, 2) phagocyte cells and 3) humoral and cellular immunity. The patients with malignant hematological diseases are exposed to complex pathogenic processes that disturb their balance, which leads to the occurrence of an infective syndrome. METHODS: In the retrospective study of 422 patients with malign hematological disease, epidemiological-clinical analysis of the infectious syndrome has been carried out. Patients were hospitalized at the Clinic for Hematology--Clinical Center of Sarajevo University, in the period from January 1, 1993 to January 1, 2000. diagnostic protocol included the following procedures: anamnesis, clinical picture, biochemical, cytomorphological, pathohistological, microbiological and radiological test. The goal of work was to determine bacteriuria in case of malign hematological diseases as an accompanying, combined complication during the treatment of these patients. RESULTS: In case of patients that were hospitalized in 1994, bacteriuria was present in the percentage of 56, which is over expected trend line whereas in 2000 it was registered in 20.65% of patients had bacteriuria while 17% of patients had have infection, 28% of patients had bacteriuria while 17% of patients had other infections. In case of patients up to 65 age, bacteriuria was more frequent in female population while in the age of over 65 it was more frequent in male population. Through microbiological analysis of urinary flora, monomicrobial bacteriuria was found in case of 58% patients, and patients were mainly in the initial phase of disease. In case of patients with long treatment with antineoplastic drugs or in the phase of advanced basic process, bacteriurias with polymicrobial character were dominant, which is characteristic of recurrent infections of urinary tract. CONCLUSIONS: The authors came to the conclusion that it is necessary to monitor urine flora with malignant hematological disease patients and by using an adequate treatment to minimize initial infection, relapse and reinfection of urinary tract. Still, it is not clear which is the basic factor initiating the infection of urinary tract--whether it is the prevailing intensity and pathogenic aggressiveness of an agent, or the exposure intensity or a supportive condition of the patient. PMID- 11769458 TI - [Hydronephrosis: comparison of conservative and surgical treatment]. AB - OBJECTIVES: Early diagnosis and identification of adequate treatment of children with hydronephrosis. METHODS: Routine ultrasound testing was followed by standard urography and micturacion cystouretrogam among those identified with hydronephrosis. RESULTS: We showed 48 children among whom the ultrasound detected hydronephrosis of various degrees. First group consists of patients with non obstructive hydronephrosis 18 patients (37.5%); the highest percentage among girls (88.3%), ages 1-5. The cause of hydronephrosis is the vesicoureteral reflux. The second group with obstructive hydronephrosis consists of 30 patients (62.5%), only one of them had obstruction ureterovesical junction. Neonatal boys dominate in this group. 50% of patients from both groups were surgically treated. CONCLUSION: Wide use of ultrasound provided for a significant improvement in diagnosis of urinary-tract anomalies. PMID- 11769459 TI - Functional alteration of brain dopaminergic system in isolated aggressive mice. AB - The present study examined the effects of social isolation on cortical dopamine (DA) release in vivo and on brain DA receptor functions to study the possible involvement of cortical DA neurons in an antiaggressive effect of the serotonin (5-HT)1A receptor agonist (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino] propoxy] 1,3-benzodioxole HCl (MKC-242). MKC-242 and the DA receptor agonist apomorphine reduced aggressive behavior in isolated mice. MKC-242 increased cortical DA release in vivo in mice, and the effect was antagonized by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2 pyridinyl)cyclohexanecarboxamide. The basal level of extracellular DA in the frontal cortex was higher in isolated mice than in grouped mice. MKC-242-induced and high K(+)-induced increases in the cortical DA release were less pronounced in isolated mice than in grouped mice. The effect of apomorphine on locomotor activity was more pronounced in isolated mice than in grouped mice. These findings suggest that the isolation stress enhances cortical DA release and the brain DA receptor function and reduces the responses of the dopaminergic terminals to 5-HT1A receptor stimulation and high K(+)-induced depolarization. PMID- 11769460 TI - [Searching for neurotransmitters as cognate ligands of orphan G protein-coupled receptor: finding receptor for melanin-concentrating hormone]. AB - The melanin-concentrating hormone (MCH) is a cyclic peptide, identified originally from salmon pituitary as a regulator of pigmentary changes in background adaptation. The rat homologue was later also found to be expressed in the lateral hypothalamus and the zona incerta. Several lines of evidence indicate that MCH is a critical regulator of feeding and energy homeostasis. Its receptor remained unknown until we identified it as the orphan G protein-coupled receptor SLC-1, using a function-based assay with G protein chimera. A wide application of our strategy will permit the discovery of more natural transmitters. PMID- 11769461 TI - [Reversal of neuronal polarity in vitro]. AB - The mechanisms for neuronal polarity are not well understood. We recently developed two experimental systems in which neuronal polarity is altered in vitro. (1) Cerebral cortical neurons of E18 rats were plated on a sheet of astroglial cells. A time-lapse analysis revealed that GABAergic neurons are highly motile. Migrating neurons often reversed their direction. The reversal of migration was accompanied with a disappearance of the growth cone at the leading process and an appearance of it at the trailing process. A translocation of the Golgi apparatus was often observed when migration was reversed. (2) To observe the reversal of neuronal polarity in vitro, we isolated neurons from the neonatal rat cerebral cortex. Neurons that exhibited an apical dendrite with a length of > 100 micro m were monitored for 3 days in culture. In 66% of the neurons examined, a new axon appeared to form from the tip of the original dendrite. The distal half of the original dendrite was converted into axons. Time-lapse video microscopy demonstrated that the axon regeneration from dendritic tips required a significantly longer time than axon regeneration from minor processes did. We hope these two experimental systems will be useful in investigating the mechanisms for neuronal polarity PMID- 11769462 TI - [Regulation of microglial cell function by ATP]. AB - Accumulated evidence suggests that extracellular ATP functions occur in neurons and glial cells in the nervous systems. Besides well-documented roles as a neurotransmitter or neuromodulator, ATP has also been demonstrated to have effects on glial cells. Reports have shown that ATP stimulates microglia to release various biologically active substances, such as interleukin-1 beta, tumor necrosis factor-alpha, and plasminogen. Microglial cell death was also demonstrated after stimulation with high-dose ATP. Although these responses were known to occur, via P2X7, we have recently found that ATP and ADP induced the formation of membrane ruffles and chemotaxis through Gi/o-coupled P2Y receptors. Taken together, it is suggested that two distinct P2X and P2Y receptor subtypes are involved in the diverse function of microglia in both physiological and pathological states. PMID- 11769463 TI - [Roles of the HNK-1 carbohydrate epitope in the nervous system]. AB - The HNK-epitope, 3-sulfo-glucuronyl residue is expressed specifically on a series of cell adhesion molecules and on some glycolipids in the nervous system over a wide range of species, and its expression is spatially and temporally regulated during the development of the nervous system. To study the biological functions of the epitope, we have cloned the enzymes that are involved in the biosynthesis of the epitope, glucuronyltransferase (GlcAT-P and GlcAT-S) and sulfotransferase (Sulf-T), A Northern blot analysis of GlcAT mRNAs in various rat tissues indicated that GlcAT-P and -S are the brain-specific or neural-specific enzymes. Upon transfection of the full length GlcAT-P cDNA into COS-1 cells, which do not express the HNK-lepitope, cells were transformed into HNK-1 positive cells. These cells showed dramatic changes of the cell architecture. They had long and branched processes with irregular shapes and several micro spikes on the soma and processes. Another function of the HNK-1 epitope is the inhibition of cell-cell aggregation. Thus control COS-1 cells formed huge aggregates after incubation at room temperature for 90 min, and most of the HNK-1 positive cells remained as free single cells. PMID- 11769464 TI - [Immune coagulation disorders (excluding antiphospholipid syndrome]. AB - During the course of replacement therapy, 22-30% of patients with severe hemophilia A develop alloantibody to factor VIII. Autoantibodies to coagulation factors rarely occur in elder individuals with previously normal hemostatic mechanisms or in patients with various underlying disorders. Although the great majority of the acquired inhibitors are directed to factor VIII, the antibodies may arise to every coagulation factor. The inhibitor antibodies directly inactivate specific clotting factor, or occasionally, they bind to a nonfunctional site, resulting in increased plasma clearance. In the last decade, we experienced 12 hemophilia A and 3 hemophilia B patients who developed factor VIII and factor VIII and factor IX inhibitor, respectively, 9 patients with autoantibody to factor VIII (acquired hemophilia), and 4 patients with acquired von Willebrand syndrome. Among 12 factor VIII inhibitors, 4 patients were identified to have inversion in the factor VIII gene, 1 with 4 bases deletion, and 1 with missense mutation resulting in G479R. Four of 9 patients with acquired hemophilia had underlying disorders of autoimmune hemolytic anemia, macroglobulinemia, urticaria, and pharyngeal cancer at the development of factor VIII inhibitor. Antibody to von willebrand factor was detected in 3 of 4 patients with acquired von Willebrand syndrome. PMID- 11769465 TI - Angiogenesis and metastasis marker of human tumors. AB - Tumor growth and metastasis are dependent on angiogenesis. Therefore, certain angiogenesis markers may be useful as metastasis markers and/or the targets for antiangiogenic therapy. We and others have been studying endoglin(EDG; CD105) for such purposes. EDG is a proliferation-associated antigen of endothelial cells and essential for angiogenesis. In addition, EDG is a component of the transforming growth factor(TGF)-beta receptor complex. Expression of EDG is up-regulated in tumor-associated angiogenic vasculature compared with normal tissue vasculature. Microvessel density detected for EDG expression in breast cancer tissues showed a statistically significant correlation with overall and disease-free survival. In addition, elevated serum EDG was associated with metastasis in patients with colorectal, breast, and other solid tumors. On the other hand, We have been targeting EDG on tumor vasculature to suppress tumor growth and metastasis by systemic(i.v.) administration of anti-EDG monoclonal antibodies(mAbs) and immunoconjugates(IMCs). To thid end, we have been using three animal models, i.e., severe combined immunodeficient(SCID) mouse model of MCF-7 human breast cancer, human skin/SCID mouse chimera model bearing MCF-7 tumor, and syngeneic metastasis model of colon-26 adenocarcinoma cells in BALB/c mice. In addition, antiangiogenic activities of anti-EDG mAbs and IMCs were evaluated in mice using the dorsal air sac assay. The IMCs were prepared by coupling deglycosylated ricin A-chain or 125I to individual anti-EDG mAbs. These anti-EDG IMCs and mAbs showed substantial antitumor efficacy and antimetastatic activities without showing severe toxicity. Recently, we generated a recombinant human/mouse chimeric anti EDG mAb to facilitate clinical application of the mAb. PMID- 11769466 TI - [Development of retrieval system about clinical laboratory handbook "Kensa Koujien"]. AB - Medical knowledge has been increasing and diversifying on a worldwide scale, while specialization of physicians has been extended vigorously. The knowledge has extended beyond the memory of human beings, there by causing the deterioration of service, called "Knowledge crisis". To tackle this problem, the electronic medical textbook(EMT) has been conceived and set up as a medical knowledge base for physician to optimize their specialties and activities in clinical practice. The doctors' diagnostic process is to be mentioned as the solution of backward problem, to speculate problem such as disease by the information observed from symptoms and findings. The EMT is more powerful tool for diagnosis than experiences or textbook that will aid for specifying the name of disease by arranging and combining information. Meanwhile, laboratory information systems are widely introduced. However, there are few systems which allow interpretation of the findings obtained. With this in mind, we have improved the utility of the EMT by enhancing its function with laboratory information follow-up, thesaurus back-up, Japanese language support, and on-line access. It made use of these experiences, we compiled an clinical laboratory handbook "Kensa Koujien", and developed retrieval system. PMID- 11769467 TI - [A systematic review for the diagnostic accuracy o serum C-reactive protein measurement in neonatal infants with infection]. AB - We presented an example of systematic review regarding diagnostic test accuracy. We compared the diagnostic accuracy of serum C-reactive protein (CRP) concentrations measured by the highly sensitive methods for neonatal infection with that by the conventional-sensitivity methods in the literatures available. Our results with the summary ROC curve indicated that the high sensitivity CRP is likely to provide a better diagnostic accuracy than the conventional methods, even though there was a heterogeneity in the specificity among studies. In the reviewing process of the literatures, we found several critical problems, such as the publishing bias and insufficient quality of primary articles. These problems may have had a substantial influence on the summary estimates. Systematic reviewing of the related articles uncovered the defects in the primary studies, requiring more prudent study designs for future clinical trials. PMID- 11769468 TI - [The introduction of a new clinical laboratory system, so-called the profiles for each diagnosis related group]. AB - We try to establish a new clinical laboratory system, so-called profiles for each diagnosis related group which have features as shown below. 1) The profiles are clinical manuals that are utilized by home doctors and show how to diagnose, follow up, observe complications and judge therapeutic effect. 2) The profiles are constructed on condition that they cover 60% of cases and cases that they cannot handle are supposed to be referred to the major hospitals or the specialized doctors. 3) The profiles are guaranteed to be reformed and maintained according to medical advancement. 4) The target diseases of the profiles are thyroid disease, liver diseases, diabetes mellitus, respiratory disease, infectious disease, renal disease, cardiac disease, hyperlipemia, collagen disease, hematological disease, osteoporosis and gynecological disease. We present the profiles for thyroid disease, hyperlipemia and collagen disease which have been accomplished. PMID- 11769469 TI - [Quantitative determination of lipoprotein by agarose gel electrophoresis and enzymatic staining of cholesterol and triglyceride: effects of age and gender]. AB - 290 normal duplicate samples (152 males and 138 females), were subjected to lipoprotein analysis by agarose gel electrophoresis to yield HDL, VLDL and LDL fractions which were respectively stained with Cholesterol and Triglyceride reagents. HDL-Cholesterol were significantly higher in female than male, and VLDL TG were significantly higher in male than female. Assay C.V.'s varied from 0.96 to 5.75 for cholesterol fractions and 2.00 to 4.34 for triglyceride fractions. Comparison of electrophoretic HDL-Cholesterol and LDL-Cholesterol concentrations with the results of a direct method (HDL-EX and LDL-EX, Denka Seiken) gave correlation coefficients of 0.967 and 0.952 respectively. This method is simple, rapid and can provide the simultaneous assessment of the cholesterol and triglyceride component in each Lipoprotein fraction. Additionally, the method is useful for evaluating lipoprotein assays. PMID- 11769470 TI - [A case of 9p-syndrome identified chromosome 20 on chromosome 9p by M-FISH]. AB - In this report, we describe one-year-old girl diagnosed with 9p-syndrome. Cytogenetic studies of this patient confirmed a karyotype of 46,XX,add(9) (p24) chromosome, but could not find the additional fragment on 9p22 in one allele. Fluorescence in situ hybridization (FISH) studies could not confirm the fragment in the patient using the LIS1 gene probe which mapped to 9p22. The more recently developed M-FISH method clearly showed that the additional fragment was 20p in this patient. These findings suggest that M-FISH analysis may be a useful method for identifying unknown additional and rearranged chromosomes. PMID- 11769471 TI - [Prostate cancer]. AB - Carcinoma of the prostate constitutes a major and escalating international health problem. In many developed countries prostate cancer is the most commonly diagnosed malignancy in men, and seems to overtake lung cancer as major cause of cancer mortality. In Japan mortality of the prostate cancer is relatively low, but future incidence and mortality of the prostate cancer will be dramatically increased. Risk factors of the prostate cancer were well known as Western-type lifestyle and diet. Carcinoma of the prostate are detected early by prostatic specific antigen and systematic trans-rectal ultrasonography guided prostatic needle biopsy. Once prostate cancer has been diagnosed in a patient, histologically graded, and staged as accurately as possible, clinicians are duty bound to offer the best advice about treatment options, even though the risks and benefits of competing therapies. Radical prostatectomy and radiation therapy are known as treatment of localized prostate cancer, antiandrogen therapy is known as treatment of advanced prostate cancer. Alternative approaches utilizing, for example microable inhibitors, inhibitor of growth factors and gene therapy also hold exciting promise. PMID- 11769472 TI - [Prostate specific antigen: a role of PSA in the diagnosis of prostate cancer]. AB - Early diagnosis of prostate cancer is best achieved using a combination of DRE and PSA as first-line tests to detect signs of prostate cancer. Because DRE and PSA do not always detect the same cancer, the tests are complementary. Among men with elevated PSA who are negative on DRE, the chance of cancer ranges from 12 to 32%. Most men with PSA elevations do not have cancer. This high false-positive rate among men without cancer has led to many approaches to decrease the incidence of false-positive test results, including PSA density, transition zone PSA density, PSA velocity, age-specific PSA reference ranges and percent free PSA. PMID- 11769473 TI - [The present status of standardization in serum total PSA measurement--a result of "Survey 2000" conducted by PSA ad hoc Committee of Japanese Urological Association]. AB - Immunoassays for serum total PSA are classified into two categories; equimolar and skewed, according to their response to free PSA and ACT-PSA. The analytical survey conducted in 1997 ("Survey 1997") revealed that more than a half of the kits displayed a skewed response which caused inter-assay variability as a major factor. PSA ad hoc committee of Japanese Urological Association chaired by Prof. H. Yamanaka carried out a survey in 2000 ("Survey 2000") in which 26 kits were participated from 18 manufacturers. Comparing with 1997, the inter-kit variability, on the whole, was remarkably reduced in 2000. The dilution tests using purified samples of free PSA and ACT-PSA elucidated that five sixths of the kits were counted to be equimolar (12; completely equimolar, 10; nearly equimolar or slightly skewed, 4; skewed). Immunological behavior of the assays to free PSA and ACT-PSA in serum samples was also markedly improved, in which free PSA content ranged to 50%. Conversion of data measured by each kit to those of Tandem R was capable in 19 kits. The remaining 7 kits were out of interchangeability, however, a measure of improvement or withdrawal of these kits would be in progress by the corresponding manufacturers. Total PSA assay is certainly going on toward standardization. PMID- 11769474 TI - [Detection of PSA mRNA in prostate cancer patients' blood]. AB - A sensitive technique using reverse transcriptase-polymerase chain reaction (RT PCR) for PSA mRNA has been used to detect circulating tumor cells in the peripheral blood of prostate cancer patients. We evaluated the clinical utility of this method for staging and monitoring for prostate cancer. The number of patients who were RT-PCR positive was increased in higher clinical stages. This technique may provide useful information for treating patients with prostate cancer, especially candidates for radical prostatectomy. Confirming the value of this modality as a prognostic factor will require further study. PMID- 11769475 TI - [Prostate cancer test and medical reimbursement]. AB - Until now there have been three diagnostic tests, prostate specific antigen (PSA, total PSA), gamma-seminoprotein (gamma-Sm), and prostate acid phosphatase (PAP), for prostate cancer. Recent progresses in utilization of PSA has resulted in two advanced tests, PSA-alpha 1 antichymotrypsin complex (PSA-ACT) and free PSA/total PSA ratio. Payment of each test ranges from 210 to 320 yen. The same as for other cancer tests, three tests is paid 440 yen, and four or more is paid 590 yen. To determine the cost effective choice, it is necessary to consult with appropriate urologists. PMID- 11769476 TI - [Autoimmune hemolytic anemia]. AB - Autoimmune hemolytic anemia (AIHA) is subclassified according to the character of the autoantibodies, however, its clinical pictures are highly heterogenous even in a given subclass. In this article, we reviewed pathogenesis, clinical and laboratory characteristics of AIHA, exemplifying data of 26 patients with autoimmune hemolysis with warm-type autoantibodies (13 AIHA, 10 Evans' syndrome, 3 systemic lupus erythematosus), and recent advances in this field. White blood cell and platelet counts varied among patients at presentation. Six of 13 AIHA patients had low reticulocyte production index (RPI) indicative of inappropriate reticulocyte response with considerable erythroblasts in the bone marrow, suggesting that ineffective erythropoiesis contributes the pathogenesis of warm type AIHA. Ten patients were judged to require red cell transfusion. Their RPI did not differ from that of patients who did not require transfusion, indicating that the degree of hemolysis is the major determinant of the severity of the disease. No significant side effects of transfusion were observed. PMID- 11769477 TI - [Investigation on apoptosis in paroxysmal nocturnal hemoglobinuria (PNH) granulocytes]. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disordr characterized by increased susceptibility of erythrocytes to complement-mediated hemolysis. Recently, PNH is a stem cell disorder with all hematopoietic lineages affected, which have deficiencies of glycosylphosphtidylinositol-anchored membrane proteins due to the phosphatidylinositol glycan-class A (PIG-A) gene abnormalities. However, it is unknown how PNH clones with PIG-A gene abnormalities increase in bone marrow. The possibility has been suggested that resistance of PNH cells to apoptosis causes the increase. We studied two-color or single-color flow cytometric analysis using Annexin V and propidium iodide or 7 amino actinomycin D for evaluation of spontaneous apoptosis in peripheral blood granulocytes from PNH patient (n = 5) and healthy volunteers (n = 5), respectively. Apoptotic granulocytes were evaluated before and after 6-, 12-, 18- and 24-hour cultures without serum. Flow cytometric analyses showed that there were no significant differences of the number of proportion of apoptotic cells between them. This fact reveals that the sensitivity of PNH cells to apoptosis is similar to that of normal cells, suggesting that PNH clones should not be increased according to resistance to apoptosis as an intrinsic characteristic. PMID- 11769478 TI - [Recent topics on basic research for idiopathic thrombocytopenic purpura]. AB - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet clearance caused by anti-platelet autoantibodies, which bind to circulating platelets resulting in destruction. by the reticuloendothelial system. We have recently developed enzyme-linked immunospot assay to detect circulating B cells secreting anti-platelet antibody. An increase in anti-platelet antibody-producing B cells in peripheral blood was specifically detected in ITP patients, but in none of thrombocytopenic patients without ITP or healthy donors. While earlier studies reported the presence of platelet-reactive T cells in ITP patients, we have recently found that GPIIb-IIIa is one of major target antigens recognized by platelet-reactive CD4+ T cells. Since GPIIb-IIIa reactive CD4+ T cells had helper activity promoting production of anti-platelet antibody, these autoreactive T cells are involved in production of pathogenic anti-platelet autoantibody in ITP patients. Suppression of GPIIb-IIIa-reactive CD4+ T cells may be of therapeutic use in treating refractory patients. PMID- 11769480 TI - [lipid metabolism abnormalities and clinical evaluation]. PMID- 11769479 TI - [Infectious mononucleosis]. AB - Infectious mononucleosis(IM) is a primary Epstein-Barr virus (EBV)infection. Since heterophil antibody negative IM is common in Japan, EBV antibody(presence of VCA-IgM or anti-EA, high titers of VCA-IgG in the absence of anti-EBNA) is useful for serologic diagnosis of IM. Although EBV causes the continuous growth of lymphoid cell lines in vitro and causes malignant diseases such as Burkitt lymphoma, nasopharyngeal cancer and malignant lymphomas in immunocompromised patients, IM is usually self-limiting, and after primary infection EBV persists in B cells throughout life without producing symptoms. In the present study, we studied CD8+ lymphocytes of patients with IM and demonstrate an increase in lymphocytes expressing HLA-DR and CD45RO, increase of intracellular pH, elevated plasma levels of sCD8, indicating activation of the subset. We also demonstrate activation of CD4+ T lymphocytes and gamma delta T lymphocytes. Activation of these immune systems in response to EBV is supposed to play an important role in assuring the benign course of IM. PMID- 11769481 TI - [Lipid metabolism abnormalities and progress in their treatment]. PMID- 11769482 TI - [Hyperchylomicronemia]. PMID- 11769483 TI - [High blood VLDL and remnant contents--diagnosis and physiopathology of complex hyperlipidemia in Japan]. PMID- 11769484 TI - [High blood LDL cholesterol contents]. PMID- 11769485 TI - [Mechanism involved and evaluation of lipid metabolism abnormalities and arteriosclerosis. Analysis by using experimental animals]. PMID- 11769486 TI - [LDL abnormalities and arteriosclerosis]. PMID- 11769487 TI - [Mechanism and evaluation of lipid metabolism abnormalities and arteriosclerosis- high blood HDL contents]. PMID- 11769488 TI - [Progress in treatment of hyperlipemia. Large-scale intervention tests]. PMID- 11769489 TI - [Progress in the treatment of hyperlipidemia. Diet and exercise therapies]. PMID- 11769490 TI - [Progress in the treatment of hyperlipemia. Drug therapy]. PMID- 11769491 TI - [Progress in the treatment of hyperlipemia. The use of various guidelines]. PMID- 11769492 TI - [Gene analysis and clinical description of lipid metabolism abnormalities]. PMID- 11769493 TI - [Pleiotrophic effect of anti-hyperlipemic agents]. PMID- 11769494 TI - [Sterol regulatory element binding proteins (SREBPs)]. PMID- 11769495 TI - [Peroxisome proliferator-activated receptor (PPAR)]. PMID- 11769496 TI - [When and how should we treat patients with abnormal lipid metabolism? A discussion]. PMID- 11769497 TI - [A recovery case of severe pancreatitis with acute respiratory distress syndrome by percutaneous cardiopulmonary support]. PMID- 11769498 TI - [An autopsied case of G-CSF producing lung cancer with bullous pemphigoid and hyper gammaglobulinemia]. PMID- 11769499 TI - [Remission of idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori: report of two cases]. PMID- 11769500 TI - [Relapsing and remitting focal myositis with fasciitis]. PMID- 11769501 TI - [A survival case of amniotic fluid embolism treated by percutaneous cardiopulmonary support and thrombolysis with tissue-plasminogen activator]. PMID- 11769502 TI - [An adult case of Lesch-Nyhan syndrome followed with long-term observation]. PMID- 11769503 TI - [Two cases of pulmonary arteriovenous fistulas with Rendu-Osler-Weber disease]. PMID- 11769504 TI - [Adult onset human herpesvirus (HHV)-7 infection presented necrotizing lymphadenitis and Sweet's syndrome]. PMID- 11769505 TI - [Primary chylopericardium]. PMID- 11769506 TI - [Two cases of relapsing polychondritis]. PMID- 11769508 TI - [Remodeling and treatment of airway lesions]. PMID- 11769507 TI - [Ischemic heart diseases and lipid metabolism: a circulation specialist's viewpoint]. PMID- 11769509 TI - [EBM and laboratory medicine]. PMID- 11769510 TI - [Standardization of laboratory medicine]. PMID- 11769511 TI - [DRG/PPS and laboratory diagnosis]. PMID- 11769512 TI - [Hospital infection control and laboratory tests]. PMID- 11769513 TI - [Prospects in telemedicine]. PMID- 11769515 TI - [Recent trends in health insurance claims]. PMID- 11769514 TI - [Present status and future of genetic diagnosis]. PMID- 11769516 TI - [New clinical laboratory tests for respiratory tract diseases]. PMID- 11769517 TI - [New clinical laboratory tests for cardiovascular diseases]. PMID- 11769519 TI - [New clinical laboratory tests for urinary tract diseases]. PMID- 11769518 TI - [New clinical laboratory tests for digestive system diseases]. PMID- 11769520 TI - [New clinical laboratory tests for hematological diseases]. PMID- 11769521 TI - [New clinical laboratory tests for endocrine and metabolism disorders]. PMID- 11769523 TI - [New clinical laboratory tests for respiratory tract infections]. PMID- 11769522 TI - [New clinical laboratory tests for immunological and allergic diseases]. PMID- 11769524 TI - [Present status and future of clinical laboratory tests(discussion)]. PMID- 11769525 TI - [Fever of unknown origin due to sclerosing mediastinitis]. PMID- 11769526 TI - [Ulcerative colitis associated with relapsing polychondritis]. PMID- 11769527 TI - [Pseudohypoparathyroidism presenting laryngospasm]. PMID- 11769528 TI - [Membranous nephropathy associated with hepatitis C virus infection]. PMID- 11769529 TI - [Cerebral sinus thrombosis associated with ulcerative colitis]. PMID- 11769530 TI - [Aldosterone and cortisol-producing adrenal tumor]. PMID- 11769531 TI - [Myelomatous ascites: an unusual presenting sign of multiple myeloma]. PMID- 11769532 TI - [IgG-kappa biclonal myeloma associated with hepatic tumor]. PMID- 11769533 TI - ["Takotsubo" cardiomyopathy with pneumothorax]. PMID- 11769534 TI - [Brugada syndrome with various changes of electrocardiogram]. PMID- 11769535 TI - [Rapidly progressive glomerulonephritis]. PMID- 11769536 TI - [Present status and future trends in the development of therapeutic agents for collagen diseases]. PMID- 11769537 TI - Findings of somatosensory evoked potential to stimulation of the sciatic nerve in two different rat strains. AB - No comparative study about somatosensory evoked potentials (SEP) on different rat strains has been done yet. It is evident that comparative SEP studies are important since different rat strains have different physiological properties. We aimed to compare early latency SEP values from stimulation of sciatic nerve in Wistar (Wr) and Sprague-Dawley (SDr) rats which are frequently used rat strains in experimental studies. In Wr group, the mean of first far field potential (Ff1) latency was shorter and the mean Ff1 amplitude was lower than that of Sprague Dawley rat group. Mean cortical potential latency in Wr group was longer than that of SDr group while amplitude was not different. Central conduction time (CCT) in Wistar rat group was found to be longer than that of SDr group. Shorter Ff1 latency in Wr group implies that afferent volley reaches cervical posterior fasciculus from sciatic nerve earlier than SDr group while longer CP latency implies that afferent volley reaches cortex later than SDr group. Similarity between the latencies of lumbar potentials implies that peripheral conduction velocity has no effect on the difference of Ff1 latencies. PMID- 11769538 TI - Production of transgenic rats using young Sprague-Dawley females treated with PMSG and hCG. AB - The aim of this study was to examine the effects of gonadotrophin treatments on estrus synchronization and superovulation in young Sprague-Dawley (SD) rats that had not yet exhibited defined estrus cycles (5 to 7 weeks old), and to produce transgenic rats using these females as embryo donors and recipients. In Experiment 1, female rats were injected with PMSG and hCG (12.5, 25, 50 and 100 IU/kg each) and were mated with stud males. The reproductive performance of young rats were highest when PMSG and hCG at doses of 25 IU/kg each were injected (delivery rate 87.5%, nursing rate 92.9%). In Experiment 2, female rats were injected with PMSG and hCG (100, 150 and 300 IU/kg each) to induce superovulation. More eggs were recovered from the rats injected with PMSG and hCG at 150 and 300 IU/kg than from those treated with 100 IU/kg (33.4 and 41.3 vs. 13.3 eggs per female, respectively; p < 0.05). In Experiment 3, pronuclear-stage zygotes from 150 IU/kg PMSG/hCG-treated rats were used for microinjection of the fusion gene of bovine alpha S1-casein gene promoter and human growth hormone gene (2.8 kb), and the microinjected zygotes were transferred into the oviduct ampullae of the 25 IU/kg PMSG/hCG-treated rats. Seventeen transgenic rats were obtained from the 334 DNA-injected zygotes (5.1%). These results indicate that recipients and embryo donors for the production of transgenic rats can be prepared by the appropriate PMSG and hCG treatments of young SD rats, regardless of their estrus stages. PMID- 11769539 TI - The difference in citric acid-induced cough in congenitally bronchial hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. AB - Cough elicitation and major physiological factors influencing cough occurrence were investigated in congenitally bronchial-hypersensitive (BHS) and hyposensitive (BHR) guinea pigs exposed to citric acid (0.3 M) aerosol for 10 min. The number of cough in BHS was significantly larger than in BHR, while the latency to cough in BHS was significantly shorter than in BHR. Pretreatment with atropine (0.2%), lidocaine (2%) or salbutamol (0.1%) aerosol and desensitization of C-fibers with capsaicin (100 mg/kg) decreased the cough numbers in both BHS and BHR. The salbutamol, atropine and capsaicin pretreatments prolonged the cough latency in BHS, but only salbutamol prolonged the latency in BHR. After salbutamol pretreatment all BHR guinea pigs exhibited cough, while 66.7% of BHS guinea pigs exhibited it. Vagal blocking by atropine suppressed coughing in both BHS and BHR. Only a small number (33.3%) of BHR guinea pigs and no BHR guinea pigs exhibited a cough response after capsaicin and lidocaine pretreatment whereas many BHS guinea pigs still produced cough after such pretreatment. The present study demonstrated that the cough responsiveness to citric acid aerosol was significantly higher in BHS than in BHR. It was revealed that airway smooth muscle contraction and functional and/or morphological development of airway nervous receptors, especially C-fiber endings, contributed to aggravation of coughing in BHS. PMID- 11769540 TI - Effects of suspension of air-conditioning on airtight-type racks. AB - Although isolation racks are superior to open-type racks in terms of securing breeding conditions for laboratory animals, the contingency-proofing capability of the former has yet to be determined. Therefore, from the view of risk management, we studied the environmental change in isolation racks by forcibly suspending ventilation and air-conditioning and confirming the maximal time length for complete recovery to the original condition after restarting their operations. The isolation racks were placed in a room that was equipped with an independent air-conditioning system. When the inside condition of the racks reached 22-24 degrees C and 59-64% of relative humidity, the air-conditioning and ventilation were forcibly suspended and the subsequent temperature, relative humidity, ammonium and CO2 concentrations in the racks were measured over time. We found that after suspending the air-conditioning and ventilation, it took 40 60 min for temperature, and about 10 min for relative humidity to exceed the maximum values (temperature and relative humidity) referred to in the Showa 58 Nenban Guideline Jikken Doubutsu Shisetsu no Kenchiku oyobi Setsubi (Guidelines of buildings and facilities for experimental animals in Japan; Year 1983 edition). After 17 hr 25 min of the suspension of air-conditioning and ventilation, two rats were found dead. Then, the air-conditioning and ventilation were restarted. It took about 2 hr for temperature, and 50 min for relative humidity to regain the guideline values. The ammonium concentration stayed within the guideline value with a maximum concentration of 2 ppm in the experimental period, whereas the CO2 concentration was found to exceed 9% at the time of animal death. PMID- 11769541 TI - Dextran sodium sulfate-induced colitis in germ-free IQI/Jic mice. AB - This study presents a histological examination of dextran sodium sulfate (DSS) induced colitis in germ-free (GF) mice. A comparison of the pathology between GF and conventionalized mice (CVz) was made to determine the role that intestinal microflora play in DSS-induced colitis. To induce colitis, GF and CVz IQI/Jic mice were given either 5% or 1% DSS orally. Administration of 5% DSS, a common concentration used to induce colitis in mice, caused gross rectal bleeding and a marked decrease in hematocrit as early as day one in GF mice. These mice died on day three due to massive bleeding into the intestinal lumen. In contrast, CVz mice did not die during the seven-day experimental period. Histopathological examination three days after administration of 5% DSS did not reveal any colitis lesions in GF mice, but CVz mice had developed moderate colitis in the large intestine. Administration of a low concentration of DSS (1%), which only induces mild basal crypt loss in CVz mice, caused severe colitis in the distal colon in GF mice, and they died on day 14. These data suggest that intestinal microflora are not necessary for the induction of colitis. Furthermore, DSS may be highly toxic to GF mice, and when given at a concentration of 5% it causes massive bleeding into the intestinal lumen resulting in death prior to development of colitis. PMID- 11769542 TI - Microbiological contamination in genetically modified animals and proposals for a microbiological test standard for national universities in Japan. AB - The Biosafety Committee of the Japanese Association of Laboratory Animal Facilities of National Universities (JALAN) investigated recent episodes of microbiological contamination in genetically modified mice (GMM), and the countermeasures taken when the contaminated GMM were introduced into animal facilities, by questionnaires addressed to 53 animal facilities belonging to JALAN and serological tests. Although almost all of the contaminated GMM were accepted with conditions such as rederivation after or before reception and housing in designated rooms, contamination with a spectrum of microorganisms was demonstrated in GMM transferred domestically and from abroad. In serological tests, Mycoplasma pulmonis, mouse parvovirus, and mouse encephalomylitis virus were detected in GMM transferred from domestic facilities and from abroad. The present results of the questionnaires and serological tests suggest that GMM are highly and widely contaminated with microorganisms compared with mice from commercial breeders. Thus, we propose a microbiological requirement, including microbiological status--excellent, common, and minimum--as a guide for the transfer and procurement of mice and rats in Japan. PMID- 11769543 TI - The daily pattern of heart rate, body temperature, and locomotor activity in guinea pigs. AB - We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), and locomotor activity (LA) in conscious and unrestrained guinea pigs using a telemetry system. HR and/or LA in some guinea pigs clearly showed circadian rhythms, but in others there were no significant daily patterns; BT did not show significant daily rhythms. These results suggest that guinea pigs might have different individual characteristics of rhythmicity, and we should, therefore, be careful when using guinea pigs in chrono-biomedical research. We believe that the results of this study may be useful for future biomedical studies using guinea pigs. PMID- 11769544 TI - A new mouse model with cochleo-saccular type inner ear defects. AB - We found a new inner ear mutant exhibiting abnormal behavior, such as circling and head shaking, in a breeding stock of SJL/J mice. The traits are inherited in a simple autosomal-recessive fashion. Animals homozygous for the responsible gene, designated cosa, show no startle response to sounds and an inability to swim. In the inner ears of cosa/cosa homozygous, but not +/cosa heterozygous adults, histopathological features of severe damage that are typical for 'cochleo saccular' or 'spotting' mutants have been demonstrated. We suggest here that the abnormal mice carry a mutation of a gene that is developmentally switched on in the early stages of development and is involved in endolymph homeostasis. PMID- 11769545 TI - Arteriosclerosis in the influx and intravisceral arteries of the liver, kidney and lung of WHHL rabbits. AB - We performed a histopathological investigation on arteriosclerotic development in the influx and intravisceral arteries of the liver, kidney and lung of male WHHL rabbits. In the influx arteries of these organs, we observed severe atherosclerotic vascular lesions with high-grade luminal stenosis. In the intravisceral arteries of the liver and kidney, no arteriosclerotic lesions were observed. However, in the intrapulmonary arteries, we recognized severe atherosclerotic vascular changes with high-grade stenosis or total obstruction of the lumen in some middle to large sized pulmonary arteries. These observations indicate that the development of arteriosclerosis in parenchymatous organs differs, and that some organs are predisposed to arteriosclerosis formation. PMID- 11769546 TI - Blood and liver lipid concentrations in EDS shrews exhibiting spontaneous non insulin dependent diabetes mellitus (NIDDM). AB - The EDS (early-onset diabetes in suncus) colony was developed as a new laboratory colony of the musk shrew and is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). We examined blood lipid (triglyceride [TG], total cholesterol [TC], phospholipid [PL], free fatty acid [FFA]) and liver lipid (TG, TC, PL) concentrations to investigate the features of lipid metabolism in these animals. All lipid concentrations examined both in blood and liver of the diabetic shrews had a tendency toward higher values than those in non-diabetic shrews. The PL concentration was the only parameter that barely showed a significant difference. Values for all blood lipid concentrations in diabetic shrews at 7-9 months tended to be higher than those of 2-month-old diabetic shrews, although the difference was not significant. These findings indicate that diabetic EDS shrews exhibit a much milder defect of lipid metabolism induced by NIDDM than other rodent models. PMID- 11769547 TI - Diabetic cataract of the musk shrew (Suncus murinus, Insectivora) exhibiting spontaneous non-insulin dependent diabetes mellitus (NIDDM). AB - The EDS colony, developed as a new laboratory colony of the musk shrew, is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). In this colony, a few diabetic shrews exhibited a cataract at 1 month after the onset of diabetes, and all diabetic shrews had bilateral cataracts at 5 months after the onset of diabetes. In contrast, cataractous animals were never observed among non-diabetic shrews. These results suggest that the cataract in the EDS colony is a diabetic complication. PMID- 11769548 TI - Two-color allele-specific polymerase chain reaction (PCR-SSP) assay of the leptin receptor gene (Leprdb) for genotyping mouse diabetes mutation. AB - An allele specific polymerase chain reaction (PCR-SSP) assay for genotyping the mouse leptin receptor (Leprdb) mutation and its wild type (Lepr+) gene was developed using two different fluorescent dye-labeled primers. First, we determined the Leprdb and Lepr+ allele by PCR-SSP assay with usual dye-unlabeled primers. However this method requires two separate PCR reactions because the amplified products specific for each allele are almost the same size. We further developed a simple and reliable two-color PCR-SSP method that uses a color complementation strategy to distinguish the Leprdb and Lepr+ alleles. Leprdb/Leprdb, Leprdb/Lepr+ and Lepr+/Lepr+ of mice (5 each) were clearly genotyped by the two-color PCR-SSP. We also performed PCR-direct sequencing for the same samples and confirmed the accuracy of this method. This method makes it possible to reduce the number of PCR reactions because both alleles are amplified in the same reaction mixture. PMID- 11769549 TI - Short-term preservation of mouse oocytes at 5 degrees C. AB - The temporary preservation of oocytes without freezing would be useful for some experiments. ICR mouse oocytes were kept in a preservation medium under mineral oil for 1, 2, 3, 4 or 7 days at 5 degrees C, and 1 or 2 days at 37 degrees C. In vitro fertilization was attempted on oocytes rinsed with TYH medium after preservation. More than 70% of morphologically normal oocytes were recovered from each preservation group. Fertilization rates of oocytes preserved for 1, 2, 3, 4 or 7 days at 5 degrees C were 69.9, 66.5, 45.3, 26.7 and 8.8% respectively. Fertilization rates of oocytes preserved for 1 or 2 days at 37 degrees C were 9.6 and 1.6%, respectively. Preservation of oocytes at 5 degrees C has some capability as a method of short-term storage without freezing. PMID- 11769550 TI - Immunohistochemical detection of tyrosine hydroxylase and concentrations of monoamines in the substantia nigra and hypothalamus of hereditary microphthalmic rats. AB - We compared tyrosine hydroxylase immunoreactivity in the substantia nigra and hypothalamus of hereditary microphthalmic rats with that of normal rats. A considerable number of neuronal cell bodies expressing tyrosine hydroxylase were present in the substantia nigra of the microphthalmic mutant as well as normal rats. Neuronal cells positive for tyrosine hydroxylase in the hypothalamus were fewer than in the substantia nigra in both rats. The concentrations of monoamines (dopamine, noradrenaline, adrenaline, and serotonin) in the substantia nigra and hypothalamus in the microphthalmic mutant were approximately the same as those of normal rats, although the diurnal fluctuation of a few monoamines was observed in normal rats. These results suggest that the metabolic aspects of catecholamine in the substantia nigra and hypothalamus of the microphthalmic mutant rat do not markedly differ from those of normal rats. PMID- 11769551 TI - Adrenal glands in small smooth-tailed tree shrew (Dendrogale murina). AB - Adrenal glands of small smooth-tailed tree shrews (Dendrogale murina), four males and two females, caught and fixed in Thailand were observed macroscopically and histologically. They were located at the cranio-medial sides of the kidney. They were elongated in shape and consisted of a cortex and medulla. The cortex could be subdivided into three zones by the cell arrangement and the morphology of nuclei, cytoplasm and cell strands, like in other mammalian species. The tree shrew seemed to share more morphological characteristics with some laboratory rodents than some of non-human primates. PMID- 11769552 TI - [Current and future concepts of echocardiography: a review laboratory technicians]. AB - We, cardiac sonographers are mostly engaged in by two-dimensional, M-mode and Doppler echocardiography. Bedside echocardiography tends to help evaluating index of cardiac function and hemodynamics quantitatively according with the progress of technique and improvement of equipment. Good examples are evaluation of left ventricle volume and regional wall motion abnormality by two-dimensional echocardiography, and systolic as well as diastolic left ventricle function and valvular stenosis and regurgitation by Doppler echocardiography. They improve the diagnostic value of cardiac echocardiography. However, many limiting factors based on error and poor indication should be taken into consideration. PMID- 11769553 TI - [Present and future of cardiac function tests: electrophysiologic tests]. AB - Various electrocardiographic and physiologic tests have been developing for almost 100 years since Einthoven established the standard 12 lead electrocardiogram(ECG) system. Recently, interest has focused on the new developing parameters associated with cardiac ventricular repolarization, such as transmural dispersion of repolarization, T wave alternans and QT dispersion. QT dispersion, measured as interlead difference of QT interval, has been suggested to reflect regional variation of ventricular repolarization. However, still unsolved basic problems give difficulties for clinical acceptance of this parameter. On the other hand, it is generally accepted that heart rate variability obtained from Holter ECG is useful tool to assess the autonomic tone. Head-up tilt test is a valuable diagnostic tool to identify patients with neurally mediated syncope and also useful for assessment of reflex cardiac autonomic function, such as baroreflex sensitivity. The number of electrophysiologic study(EPS) dramatically increased together with increase of radiofrequency catheter ablation. A new three-dimensional nonfluoroscopic electroanatomical mapping system(CARTO) is an exciting development in catheter ablation treatment. Transtelephonic ECG and its computer-assisted answering system are also useful for diagnose and treatment in the patients of paroxysmal cardiac symptoms. PMID- 11769554 TI - [Respiratory function tests--current and future perspective]. AB - The apparatus for the respiratory function test have recently made a great progress and become very easy to handle owing to the development of computer technology and medical ordering system. However, the respiratory function tests depend its result on the cooperation of patients. Thus, it is important for the medical technician to obtain the maximum efforts and cooperation of the patients in the testing. In the sense, the standardization of the testing should be done urgently regarding procedures, softwares, hardwares and maintenance of apparatus. In the future perspectives, we would like to emphasize following 3 points. First, more noninvasive and sophisticated testing methods and instruments should be developed, since the patients' age will become more and more old and vigorous active cooperation may not be possible for the assessment of respiratory function. The testing for the transplantation of lung should also be developed. Second, the development of screening test and its performance for the routine medical check for the local inhabitants have been important for the early detection, treatment, and follow up of respiratory diseases. Finally, the medical technician should be prepared so that the testing is available when it is needed. PMID- 11769555 TI - [Pulmonary function tests and their clinical significances on outside of textbooks]. AB - Pulmonary functions are classified two kinds of functions which are respiratory and non-respiratory. We explained new clinical significant results by looking at the usual respiratory pulmonary function tests and devices in this paper. We found two new indexes on uneveness of ventilation by analyzed compartments of forced expiratory curves(Tiffneu curves) and at improvement of CO single breathing method on diffusing capacity test. We found new index on bronchial anaphylaxis for bronchial asthma by time constant measured from forced expiratory curves, also. We found new index on ventilatory efficiency at developing the automatic respiratory resistance meter by the forced oscillation method of Du Bois, too. PMID- 11769556 TI - [Clinical laboratory's trends in the 21st century]. AB - The new century presents numerous challenges and opportunities for the clinical laboratory scientists. Japan's economic recession has affected health care system directly. Clinical laboratories in particular have been hard hit financially. Laboratory people have striven for financial efficiency and balance within their own fields but now must broaden their view beyond this familiar field to the wider sphere of economics and medicine as whole. As laboratory professionals, we must be able to anticipate and respond to the current changes in disease frequencies, the fewer number of children in the nation, the health needs of the aging society, and the resulting economic implications. We, Japanese scientists, bring into the 21st century two major achievements. One is establishment of a fully automated laboratory system equipped with a transfer module. The second is reduced variation in inter-laboratory test results. Greater uniformity in the test results has been provided for by the supply of certified and calibrated reference materials as well as the dissemination of standard procedure for the measurement of catalytic amounts of enzymes published by the Japan Society of Clinical Chemistry(JSCC). Advances in the fields of diagnostic imaging were marvelous and received widespread attention. No less important were advances in high sensitivity immunoassay systems molecular biology-based diagnostic systems, and miniaturization of laboratory systems. The immediate future of laboratory medicine will be built upon these advanced technologies. PMID- 11769557 TI - [Reference values of serum lipid]. AB - The guideline for the reference value of serum lipid(total cholesterol, LDL cholesterol, HDL-cholesterol and triglyceride) was proposed by the Japan Atherosclerosis Society in 1997. These values are utilized for the diagnosis and treatment of hyperlipidemia to protect patients from ischemic heart disease. The upper limit of reference value was not determined by the 95 percentile range from healthy subjects, but on the basis of clinical data on serum lipid in the Japanese. This way to determine the reference value will be suitable in case of lipid, because there is a tendency to increase cholesterol level in the Japanese for these thirty years. The standardization for each lipid assay is crucial. The CDC-established Reference Methods for measuring total cholesterol(TC), HDL-C. LDL C, and triglyceride(TG) are used to set reference values for the serum pools used for LSP(Lipid Standardization Panel) standardization. In Japan, the routine methods for cholesterol and triglyceride have been proposed by the special committee in the Japan Society of Clinical Chemistry. In contrast, homogeneous assay for HDL- and LDL-C, which are used routinely at present, have still some problems in the point of accuracy. A new ELISA for Lp(a) has been developed using antibody not reacting to kringle IV type 2. Its standardized assay, thus, will be available sooner or later. With respect to other lipid-related test such as RLP(remnant-like particles) and oxidized LDL, it is necessary to accumulate more clinical data for the determination of reference value. PMID- 11769558 TI - [Implication on thyroid function tests]. AB - We tried to investigate the present problems, concerning the reference individual and interval in thyroid function tests and find the solutions for them. We are now using healthy adults for the reference individual and interval. Recently, we found the sex-difference and age-related changes for reference individual and interval in free T3 measurement. We raised the questions on whether there are any sex-differences and/or age-related changes or not. Surprisingly, there were almost no detailed data about them especially in Japan. Therefore, we examined the Europe data, and found out some kind of sex-differences and age-related changes. We propose the following examinations using many Japanese population in order to provide a precise and proper reference individual and interval: 1. Whether there are any sex-difference in thyroid function tests? 2. Whether there are age-related change in thyroid function tests, for instance, simply dividing population into the immature, adult and the aged? PMID- 11769559 TI - [Identification and epidemiologic investigation of bacteria by the Riboprinter Microbial Characterization System, the automated ribotyping system]. AB - An automated ribotyping system, RiboPrinter Microbial Characterization System(Qualicon), was evaluated as a typing tool. Strains used in this study is as follows; 40 strains of methicillin-resistant Staphylococcus aureus (MRSA) with 40 distinct PFGE patterns, 20 MRSA from two hospital ward with suspicion of outbreaks, 53 strains of Escherichia coli including 43 strains of pathogenic E. coli, and 50 strains of Streptococcus pyogenes including 31 strains from patients with severe streptococcal disease. Typeability was 100%. Excellent result was obtained in identificating E. coli including Enterohemorrhagic E. coli O157, but poor in two species of gram positive cocci. Concerning discriminatory power, the RiboPrinter was generally less sensitive than PFGE in identifying different strains, but good correlation with strain relatedness by PFGE and antigenic classification. RiboPrinter surpassed PFGE at handling, result interpretation, and rapidity, therefore, hierarchical approach with the first pass through the RiboPrinter followed by PFGE as the occasion demands can be very useful to save labor. The RiboPrinter has the potential to be a widely useful tool in molecular epidemiology. PMID- 11769560 TI - [Clinical application of new ultrasonographic technology]. PMID- 11769561 TI - [A new development of clinical laboratory]. PMID- 11769562 TI - [Characterization of cryoglobulin, M protein, low molecular weight IgM in a patient with chronic hepatitis C and type II mixed cryoglobulinemia]. AB - The common extrahepatic manifestation of hepatitis C virus(HCV) infection is mixed cryoglobulinemia. We have analyzed serum cryoglobulin, IgM and various antibody activities from a patient with chronic hepatitis C and type II cryoglobulinemia. Cryoprecipitates were consisted of polyclonal IgG and monoclonal IgM-kappa with rheumatoid factor activity. About 20% of total IgM was found to be low molecular weight IgM by gel-filtration and SDS-PAGE. The anti streptolysin O(ASO) activity measured by Latex agglutination method was found to be markedly elevated despite normal activity by Rantz-Randell method. The patient's serum has revealed to react against bovine gamma globulin, which crosslinked streptolysin O to Latex particles, in a nonspecific manner. Phenotypic analysis of the surface markers on abnormal lymphoid cells from peripheral blood and bone marrow showed monoclonal expansion of B-cell lineage by flow cytometry. The patient was treated with interferon-alpha, which resulted in an improvement of liver dysfunction, decreased amounts of cryoglobulin and IgM. It was concluded that the patient has suffered from lymphoproliferative disorder, namely HCV infection-associated primary macroglobulinemia. PMID- 11769563 TI - [Increased serum PIVKA-II levels in hyperthyroidism]. AB - PIVKA-II has been practically used as a tumor marker of hepatocellular carcinoma. On the other hand, increased serum PIVKA-II concentration was reported in a Japanese patient who had hyperthyroidism without liver diseases. To evaluate whether thyroid hormone is related with serum PIVKA-II, we examined serum PIVKA II concentrations in patients with various thyroid diseases. Eight patients with Hashimoto disease, 24 patients with Graves' disease, and 8 healthy subjects were studied. There was no significant difference of serum PIVKA-II levels among the three groups. However, serum PIVKA-II concentrations(mean +/- SD mAU/ml) in hyperthyroidism(37 +/- 27) were significantly higher than those in hypothyroidism(16 +/- 9) and normal controls(12 +/- 4) (p < 0.05 and p < 0.01, respectively). When hyperthyroid patients were treated by antithyroid drug or isotope, serum PIVKA-II concentrations decreased in accordance with the decrease of serum FT4 concentrations. Our data indicate that serum PIVKA-II concentration was increased in patients with hyperthyroidism, but further in vivo studies are necessary to clarify the mechanism related to increased serum PIVKA-II by thyroid hormone. PMID- 11769564 TI - [Association study on candidate loci of susceptible genes of autoimmune thyroid diseases in a Japanese population]. AB - Autoimmune thyroid diseases(AITD), which include Graves' disease(GD), Hashimoto's thyroiditis(HT), primary hypothyroidism with blocking-type anti-thyrotropin receptor antibody and idiopathic myxedema, are believed to be a multifactorial disease with a significant genetic and environmental component. Several genetic factors associated with AITD susceptibility have been tentatively identified, including the HLA genes and the cytotoxic T lymphocyte associated-4(CTLA-4) gene. More recently, as part of a genome scan, five additional chromosomal locations, i.e., chromosome 5, 8, 9, 15 and X, have recently been reported in a Japanese population. In the present study, in order to confirm evidence obtained by the genome scan, we performed an association study regarding these five candidate loci identified as regions where susceptible genes of AITD exist. Five microsatellite markers, which are located in these loci, were genotyped in a set of 487 unrelated Japanese AITD patients and 218 Japanese controls. Markers located in chromosome 5, 15 and X showed association in AITD patients with significant increase in particular alleles (p < 0.01), while markers in chromosome 8 and 9 did not consistently show significant association. These findings partly support evidence by the previous genome scan that attempted to identify loci of susceptible genes of AITD in a Japanese population; presence of an AITD susceptibility locus at 5q31-33 was suggested. Genotyping using other markers located in these loci would be helpful not only to confirm regions of AITD susceptible genes but also to narrow the regions. PMID- 11769565 TI - [A study of serum mitochondrial enzymes(mCK, mAST, mMDH) in rotavirus and adenovirus gastroenteritis in pediatric patients]. AB - Rotavirus and adenovirus antigens in feces from 77 cases of gastroenteritis in pediatric patients were examined. Mitochondrial enzymes, mitochondrial creatine kinase(mCK), mitochondrial aspartate amino-transferase(mAST) and mitochondrial malate dehydrogenase(mMDH) activities in their sera were also measured and compared with the results of rotavirus and adenovirus antigens in the feces. Thirty-one cases were rotavirus antigen-negative(rota-negative)/adenovirus antigen-negative(adeno-negative), 5 were rota-negative/adenovirus antigen positive(adeno-positive), 40 were rotavirus antigen-positive(rota-positive)/adeno negative, and only one case showed positive for both antigens. The mean activities of these three enzymes were compared among 3 groups except one both positive case mentioned above and control group(n = 105) by Mann-Whitney U-test. The serum mCK activity was significantly higher in rota-positive/adeno-negative patients than in other groups(p < 0.01). On the other hand, no significant differences were observed for mAST and mMDH activities among any groups. It is suggested that these phenomena are caused by the differences of localization of these enzymes in mitochondria, that mCK is located the outer surface of inner membrane of mitochondria, and mAST and mMDH are located on the inner surface. The difference of serum mCK activity between rotavirus infection and adenovirus infection suggests that intestinal epithelial cell injury by rotavirus is stronger than that by adenovirus. PMID- 11769566 TI - [Analysis of correlation between physical training and autonomic function by using multivariate analysis: establishing an indicator of health]. AB - The purpose of this study is to assess the effects of physical training on autonomic nervous function. Twenty-two healthy subjects(12 males and 10 females) participated in this study. We inquired contents of the exercise for each subject. Continuous ECG was recorded during 320 seconds at supine resting. Respiratory rhythm was fixed at 0.25 Hz(15 time/min). On the basis of spectral analysis of heart rate variability, the autonomic nervous function was assessed by low frequency power(LF: 0.06-0.13 Hz) and high frequency power(HF: 0.16-0.50 Hz). The predominance of sympathetic nervous activity were indicated by the LF/HF and LF-HF. Relationship between physical training and autonomic function was analyzed by using multivariate analysis(partial correlation analysis). As the results, LF power and LF-HF negatively correlated with training time per day, energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). HF power positively correlated with energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). These results indicate not training time but energy expenditure alters the autonomic nervous function. This index may be useful for evaluating training effect on the promotion of health. PMID- 11769567 TI - [Endocrine disruptors and brain estrogen receptors: the current state of behavioral, neurochemical, and molecular biological studies]. AB - Based on epidemiological studies and animal studies, endocrine disrupters have received considerable attention as exerting disrupting actions on the developing brain. On the other hand, there has been increasing evidence that sex hormones and thyroid hormones play important roles in the development of the brain, including sexual dimorphism during the perinatal stage. Thus it seems probable that perinatal exposure to endocrine disruptors, which may have an affect on biosynthesis, transport, action, and metabolism of the hormones, may disrupt brain development enough to impair the brain functions. In this review, we introduce the current state of studies on brain disrupting actions of endocrine disruptors, addressing their actions on the estrogen system, including our own findings. The outline of the findings thus far reported are as follows: (1) Perinatal exposure to relatively low concentrations of endocrine disrupters may cause an impairment of higher brain functions, such as sexual behavior and learning behavior, (2) There seems to be sexual difference about the impairment described above, (3) Endocrine disruptors may cause an increase in volume of some nuclei, such as the sexual dimorphic nucleus of the preoptic area and locus coeruleus of the brain, (4) The disruptor might change the level of some substances that are considered to be involved in synaptic functions. Much remained to be studied about how does each finding reported link the others, and about detailed mechanisms of the disrupting actions of endocrine disruptors on the developing brain. PMID- 11769568 TI - [The stress-reducing effect of cigarette smoking and the influence of trait anxiety on its manifestation]. AB - The purpose of the present study was to clarify the stress-reducing effect of cigarette smoking and the involvement of other factors such as trait-anxiety on the above effect of smoking. The subjects were 32 smokers who met DSM-IV criteria for substance dependence and 16 nonsmokers. The smokers were randomly assigned to a smoking group or a sham-smoking group. Immediately after the subjects performed a laboratory task, the State-Trait-Anxiety Inventory was administered for evaluating the levels of state-anxiety and trait-anxiety. The subjects were required to smoke a cigarette in a smoking group, sham-smoke in a sham-smoking group, or take a rest in a nonsmokers's group. After that, the same inventory was again administered. The decrease of state-anxiety in a smoking group was significantly more marked in degree than in a sham-smoking group and was comparable to that in a nonsmokers' group. A stepwise regression analysis revealed that the trait-anxiety levels significantly contributed to a decrease of state-anxiety levels in a smoking group. The present study indicated that cigarette smoking exhibited a stress-reducing effect and that the trait-anxiety levels were related to the effect of smoking. PMID- 11769569 TI - Selective 5-HT1A receptor agonist, 8-OH-DPAT, locally administered into the dorsal raphe nucleus increased extracellular acetylcholine concentrations in the medial prefrontal cortex of conscious rats. AB - The effects of a selective 5-hydroxytryptamine (5-HT)1A receptor agonist, 8 hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), directly administered into the dorsal raphe nucleus (DR) on acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) of freely moving rats were investigated by using a microdialysis technique. 8-OH-DPAT (1.0 and 5.0 micrograms) administered into DR significantly increased extracellular ACh concentrations in mPFC in a dose-dependent manner with a maximal increase to 215% and 237% of basal level, respectively, whereas a 0.1 microgram dose of this drug failed to exert such an increase. The present study suggests that the stimulation of somatodendritic 5-HT1A autoreceptors in DR is involved in an enhancement in ACh release in mPFC. PMID- 11769570 TI - Molecular mechanism of cholinergic dysfunction and cognitive deficits induced by amyloid beta-peptide. AB - Amyloid beta-peptide (A beta) plays a critical role in the development of Alzheimer's disease (AD). Much progress has been made in understanding this age related neurodegenerative disorder; thus an insight into the cellular actions of A beta and resulting functional consequences may contribute to preventive and therapeutic approaches for AD. In this review, recent evidence of A beta-induced brain dysfunction, especially cholinergic impairment and memory deficits, is summarized. Moreover, proposed mechanisms for A beta-induced neurotoxicity such as oxidative stress, ion-channel formation, and A beta-receptor interaction are discussed. PMID- 11769571 TI - Pathophysiology and management of irritable bowel syndrome. PMID- 11769572 TI - What is the best method to diagnose Helicobacter infection in bleeding peptic ulcers?: a prospective trial. AB - BACKGROUND: It has been debated which diagnostic test should be preferred for the diagnosis of Helicobacter pylori (HP) in patients with peptic ulcer diseases. Several limitations are reported in bleeding peptic ulcers because of intragastric blood and possibility of changed numbers of organisms by medication. This study was designed to find out the best method for diagnosis of HP infection, in aspect of deciding the times of detection and the specific tests in bleeding peptic ulcers. METHODS: We prospectively examined histology, rapid urease test (CLO test), urea breath test (13C-UBT) and serology in HP diagnostics in 32 patients with bleeding peptic ulcers to detect HP infection. Each test was performed two times (four methods at first 24 hours and former three methods at 7th day after initial therapeutic endoscopy). We evaluated the sensitivity of each test, compared the two-times results and evaluated the effect of these tests to an outcome of endoscopic hemostasis. RESULTS: Diagnostic sensitivities of histology, CLO test, 13C-UBT and serology are 75%, 67.8%, 100% and 100% at first endoscopy, and 71.4%, 78.5%, 89.3% at 7th day endoscopy, respectively. Histologic study and CLO test had diagnostic limitation at emergent first endoscopy contrary to UBT (p < 0.01). Histologic study, CLO test and UBT have limitations at 7th day endoscopy. Only 3 patients (9.4%) rebled with subsequent complete endoscopic hemostasis and all diagnostic tests at initial endoscopy did not influence the outcome of hemostasis. CONCLUSION: First day histologic and CLO tests are inadequate methods in detecting HP infection in patients with bleeding peptic ulcers. 7-day histologic, CLO test and UBT have a low sensitivity. First-day UBT can be a standard test to diagnose HP infection in patients with bleeding peptic ulcers. PMID- 11769573 TI - Seroepidemiology of HBV infection in South Korea, 1995 through 1999. AB - BACKGROUND: We analyzed serologic data that were obtained from the Korea Association of Health from 1995 to 1999 to estimate the reliable prevalence of HBV in South Korea. METHODS: 603,375, 639,465, 621,476, 612,705 and 650,398 serum samples were annually tested for HBsAg. Of HBsAg positive persons whose serum samples were available, HBeAg positivity was checked. RESULTS: HBsAg positivities among subjects between 6 and 19 years old were 8.2%, 3.9%, 2.1%, 2.6% and 1.3%. HBsAg positivities among subjects above 20 years old were 8.9%, 6.4%, 5.9%, 5.4% and 5.4%. The positive rates of HBeAg were 39.8 to 62.9% among subjects between 6 and 19 years old, and 18.3 to 37.9% among persons above 20 years old, in each year. In both subgroups, HBsAg positivity in the latter year was significantly lower than that in the former year (p < 0.001). It also showed that HBsAg positivities among subjects between 6 and 19 years old have been significantly lower than those among subjects above 20 years old, but those of HBeAg the exact reverse of HBsAg since 1996 (p < 0.001). CONCLUSIONS: It was observed that prevalence of HBV infection in the late 1990s, especially in the group between 6 and 19 years old, was conspicuously lower than that in the past. The nationwide vaccination programme might be one of the most important contributors to this tendency in Korea. PMID- 11769574 TI - Ultrastructural changes of hepatic stellate cells in the space of Disse in alcoholic fatty liver. AB - BACKGROUND: Hepatic stellate cell (HSC) has been suggested to play a role in fibrogenesis in alcoholic liver disease. We evaluate the correlation with fibrogenesis and ultrastructure of hepatic stellate cells in alcoholic fatty liver. METHODS: We studied 6 patients with alcoholic fatty liver and 5 non alcoholic fatty liver. The numbers of fat droplets in hepatic stellate cell was determined by electron microscopy. We also studied the grading of deposition of collagen fibers in the space of Disse. We were to evaluate the structure of hepatic stellate cells in the space of Disse by light and electron microscopy. RESULTS: Wider distribution of fat droplets in hepatic stellate cells in alcoholic fatty liver than in normal liver. The hypertrophied endoplasmic reticulum in hepatic stellate cells is a prominent findings in alcoholic fatty liver. We observed basement membrane-like materials in patients with alcoholic fatty liver with hepatic fibrosis. CONCLUSION: The results demonstrate that, in patients with alcoholic fatty liver by alcoholic liver injury, the hepatic stellate cells may play an important role in the fibrogenesis of perisinusoidal spaces in the liver. PMID- 11769575 TI - Mucin secretion in the rat tracheal epithelial cells by epidermal growth factor and Pseudomonas aeruginosa extracts. AB - BACKGROUND: Hypersecretion of mucin due to goblet cell hyperplasia is frequently encountered in many chronic airway diseases, such as chronic bronchitis, bronchiectasis, bronchial asthma and cystic fibrosis. Even in normal individuals, viral infection or bacterial pneumonia frequently provoke huge amounts of bronchial secretions which may cause airway obstruction. The production of mucin was regulated by epidermal growth factor (EGF) in vitro. To know whether this EGF system regulates mucin secretion in vivo and Pseudomonas also stimulates the mucin secretion by the same pathway, we studied these relationships in the cultured rat tracheal epithelial cells. METHODS: Rat tracheal epithelial cells were obtained by pronase dissociation from the male Fisher 344 rats. When cells became confluent, they were divided into 6 groups and stimulated with either EGF for 24 hours or Pseudomonas extracts for 12 hours with or without selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478. RESULTS: We found that both EGF and Pseudomonas extracts phosphorylated the tyrosine residue in the EGF receptor from the rat tracheal epithelial cells and this tyrosine phosphorylation was nearly completely blocked by selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478. The mucin secretion was also stimulated by either EGF or Pseudomonas extracts but more strong secretion of mucin and MUC5AC gene expression in the rat tracheal epithelial cell was done by Pseudomonas extracts. CONCLUSION: These data suggest that Pseudomonas secretes the mucin by way of the EGF receptor and MUC5AC gene expression and the inhibitors of EGF receptor tyrosine phosphorylation would be useful to prevent the huge production of mucin due to Pseudomonas aeruginosa lung infection. PMID- 11769576 TI - Drug-resistant tuberculosis in a tertiary referral teaching hospital of Korea. AB - BACKGROUND: Resistance of Mycobacterium tuberculosis strains is an increasing problem worldwide. Our purpose was to determine the prevalence of drug resistance (DR) and risk factors of DR in patients with tuberculosis and to assess the clinical characteristics and socioeconomic status of patients with drug-resistant tuberculosis. METHODS: We retrospectively studied drug susceptibility tests and clinical and socioeconomic records for 308 cases of culture-positive Mycobacterium tuberculosis infection, diagnosed at Mokdong Hospital, Ewha Womans University from March, 1995 to February, 2000. RESULTS: DR to at least one drug was identified in 75 (24.4%); the rate of primary DR, 18.7% and acquired DR, 39.3%. Multi-drug resistance (MDR) was identified in 31 (10.1%); primary MDR, 7.0% and acquired MDR, 21.4%. The risk factors of DR were previous TB treatment, pulmonary involvement and associated medical illness. DR group showed lesser adherence to treatment than the drug-sensitive group. DR group showed more frequent self-interruption of medication, lower completion rate of treatment and higher failure rate of follow-up than the drug-sensitive group. In previously treated tuberculosis patients, higher rate of overall DR and MDR, larger number of resistant drugs and more frequent self-interruption of medication were observed than newly diagnosed patients. Among DR group, acquired DR (ADR) group was older, less educated and treated for longer duration and had more advanced disease than primary DR group. CONCLUSION: Previously treated tuberculosis is a most important risk factor for DR. DR group, especially ADR, showed less compliance with treatment. More proper education and attention to prevent self interruption should be given to a previously treated group. In TB prevalent areas, it should be considered to obtain initial drug susceptibility testing in high risk of DR. PMID- 11769577 TI - Effects of BCG infection on Schultz-Dale reaction, allergen-specific IgE levels, and Th2 immune response in sensitized rats. AB - BACKGROUND: BCG, a potent inducer of Th1 immune response, has been suggested to suppress Th2 response which is known to mediate IgE-mediated allergic disorders, in particular allergic asthma. Schultz-Dale reaction is known to be a model of IgE-mediated hypersensitivity. This study was done to investigate whether BCG infection suppresses the Schultz-Dale reaction by inhibiting Th2 response and allergen-specific IgE production. METHODS: Twenty-four Sprague-Dawley rats were sensitized and provoked with ovalbumin (OVA). A pretreatment of 6 x 10(4) colony forming units of BCG or saline was done 7 days before sensitization. The Schultz Dale reaction was represented as tracheal smooth muscle contractions to 50 micrograms/mL OVA challenge in vitro. Serum OVA-specific IgE levels and IFN-gamma and IL-4 concentrations in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The Schultz-Dale reaction and serum OVA-specific IgE levels were significantly decreased in BCG infected and OVA sensitized rats compared with only sensitized rats (p < 0.01 and p < 0.05, respectively). As compared with only sensitized rats, IL-4 concentration and a ratio of IFN-gamma:IL-4 in BCG infected and OVA sensitized rats were significantly decreased (p < 0.001) and increased (p < 0.05), respectively. The Schultz-Dale reaction was correlated with OVA-specific IgE levels (r = 0.50, p < 0.05), IL-4 concentration (r = 0.69, p < 0.001), and ratio of IFN-:IL-4 (r = -0.44, p < 0.05). OVA-specific IgE levels were correlated with IL-4 concentration (r = 0.61, p < 0.01) and ratio of IFN-gamma:IL-4 (r = 0.48, p < 0.05). CONCLUSION: These findings suggest that BCG infection prior to allergen sensitization may inhibit Schultz-Dale reaction developed in the sensitized rat tracheal smooth muscle via the suppressive effects of Th2 immune response and allergen-specific IgE production. PMID- 11769578 TI - Clinical significance of classification of Graves' disease according to the characteristics of TSH receptor antibodies. AB - BACKGROUND: It has been widely accepted that the epitope(s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves' patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluated yet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves' disease. METHODS: We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1 + 2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves' disease. RESULTS: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n = 41) was characterized by moderate TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n = 16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n = 19) patients had low TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n = 30) could be categorized as 'mild disease' group, as they had low activities in all kinds of TSHRAb assay and had low antimicrosomal antibody activities. 5) Group 5 (n = 14) was characterized by moderate TSAb activities with atypical epitope(s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n = 10) patients had very high TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n = 6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p < 0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p < 0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50% vs. 27.5%, p = 0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. CONCLUSION: These results suggest that the differences in epitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves' disease. Although the pathogenic mechanism is not clear yet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves' disease. PMID- 11769579 TI - Intrathoracic malignant peripheral nerve sheath tumor in von Recklinghausen's disease. AB - Malignant peripheral nerve sheath tumor (MPNST) is defined as any malignant tumor arising from or differentiating toward the cells of the peripheral nerve sheath. MPNST accounts for about 5-10% of all soft tissue tumors and is often associated with neurofibromatosis type I (NF-1, von Recklinghausen's disease). It is one of the malignant tumors associated with von Recklinghausen's disease. Its common site is the lower and upper extremities, trunk, head and neck. But intrathoracic manifestations are very rare. We report a case of a 40 year-old man with multiple neurofibromatosis who was presented with an intrathoracic malignant peripheral nerve sheath tumor. PMID- 11769580 TI - A case of spontaneous pneumomediastinum and pneumopericardium in a young adult. AB - Spontaneous medialstinal emphysema (pneumomediastinum) and pneumopericardium may be defined as the presence of free air or gas in the mediastinal structures and in the pericardial sac without an apparent precipitating cause. It most frequently occurs in young healthy adults without serious underlying pulmonary disease. Although pneumomediastinum and pneumopericardium is often asymptomatic, it may cause pain in the neck and chest, dysphonia and shortness of breath. Treatment is supportive unless the patient has a history of trauma from foreign body aspiration. The course of spontaneous pneumomediastinum and pneumopericardium is usually benign and self-limited. A case of spontaneous pneumomediastinum, pneumopericardium and subcutaneous emphysema in a 20-year-old male is reported in this paper. PMID- 11769581 TI - Systemic lupus erythematosus presenting earlier as retinal vaso-occlusion. AB - Retinal vascular lesions are the most common ophthalmologic manifestation of systemic lupus erythematosus (SLE), occurring in 3% to 29% of cases, generally late in the disease. More rare is the severe vaso-occlusive disease, often termed "retinal vasculitis", which includes central retinal artery occlusion, multifocal arteriolar occlusions, extensive capillary nonperfusion and central venous occlusion. Patients with SLE and raised serum concentrations of anticardiolipin antibodies (ACA) have a higher risk of developing occlusive ocular vascular disease. We report a case in which retinal involvement was an earlier manifestation of SLE in a patient without ACA. PMID- 11769582 TI - A case of glomerulonephritis in association with pyogenic liver abscess. AB - Glomerulonephritis associated with visceral abscess is being increasingly recognized. The association of glomerulonephritis with visceral suppuration in the absence of endocarditis was first described by Whitworth and associates. Abscesses were most frequently located in the respiratory tract but have been reported at numerous other sites, including appendix, uterus, aorto-femoral bypass graft and cutaneous wound. This report documents the apparently rare occurrence of glomerulonephritis with acute renal failure in association with pyogenic liver abscess. The need for awareness of glomerulonephritis as a cause of acute renal failure in pyogenic liver abscess is highlighted. PMID- 11769583 TI - Sweet's syndrome during the treatment of acute promyelocytic leukemia with all trans retinoic acid. AB - All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet's syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet's syndrome associated with ATRA is found, physicians will have to face a great challenge over the possibility of infectious conditions. We present here a case of Sweet's syndrome associated with ATRA. A 35-year-old female with APL developed fever, painful erythematous cutaneous plaques on both cheeks, right wrist and both shins during induction chemotherapy with ATRA. A skin biopsy revealed a dense dermal infiltrate, consisting of mature neutrophils without vasculitis or cutaneous immunoglobulin deposits, which is compatible with Sweet's syndrome. Oral prednisone was administered and the lesions started to improve within 48 hours. PMID- 11769584 TI - Medical groups. In the red zone. PMID- 11769585 TI - Outpatient PPS. Incoming APCs. PMID- 11769586 TI - Diagnostic imaging. Bond. X-ray bond. PMID- 11769587 TI - Information technology. Paperless practice. PMID- 11769588 TI - Information technology. Computing that's out of this world. PMID- 11769589 TI - Health literacy. Wasted words. PMID- 11769591 TI - Growing revenue. AB - You've cut and cut and cut costs; sometimes it feels that if your cut any more, you'd hit bone. But the financial pressures haven't relented, and there's no sign they will any time soon. So hospitals are recognizing that cost-cutting is fine as far as it goes, but the time has come to cultivate new sources of revenue. They're looking under all the usual rocks--coding their reimbursement claims more effectively, negotiating better contracts with managed care companies and stepping up collection efforts--and seeking ways to reemphasize profitable services. PMID- 11769590 TI - Are you ready? AB - Like the public, health care leaders might feel overwhelmed by the prospect of preparing for a terrorist act, especially one involving biological agents. In our 10-page special report, we look at practical steps you can take today to get ready, drawing lessons from hospitals in New York City, Washington, D.C., and Israel, and from Salt Lake City's efforts to prepare for the possibility of terrorism at the Olympics in February. Please note that our report is based on the latest news about terrorism, reaction to it and readiness efforts as of H&HN's deadline. PMID- 11769592 TI - AHA environmental assessment. AB - The first step in planning is to assess your environment. Ask the long-range questions: What does your current market look like? What are the demographic trends that will influence your community? How will the workforce issue and the regulatory environment affect your hospital? Hospitals & Health Networks presents the American Hospital Association's environmental assessment, which may help you to conduct your own. PMID- 11769593 TI - The front line. Local hospitals will be the first to respond to a terrorist attack--and they intend to be ready. PMID- 11769594 TI - Intracranial aneurysms: experience in treating 500 patients. AB - OBJECTIVE: To summarize the experience in surgical treatment of patients with intracranial aneurysms. METHODS: The measures used in the treatment of 500 patients with intracranial aneurysms were retrospectively reviewed with regard to timing of surgery, induced-hypotensive anesthesia, brain protection combined with temporal occlusion of the feeding artery, dynamically monitoring of transcranial Doppler ultrasound, antivasospasm treatment, techniques of direct surgery, and endovascular embolization. RESULTS: In 465 patients undergoing surgery, intraoperative rupture was observed in 27(6.2%), postoperative death in 13 (2.7%), hemipalsy in 8(2.2%), and vegetative state in 2 (5.0%). The operative mortality was 3.8% in 210 patients before 1990, while 1.9% in 255 patients after 1990. CONCLUSION: The outcome of patients with intracranial aneurysms can be markedly improved by comprehensive measures. PMID- 11769595 TI - [3-D angiography in diagnosis and treatment of intracranial aneurysm]. AB - OBJECTIVE: To summarize the results of initial application of three-dimensional angiography (3D-Angio) in diagnosis and treatment of intracranial aneurysms. METHODS: From August 1999 to January 2001, standard digital subtraction angiography (two-dimensional angiography, 2D-Angio) and 3D-Angio(obtained by reconstruction of rotational angiography) were performed in 65 patients with confirmed or suspected aneurysms. RESULTS: Sixty-six aneurysms were found in 60 patients and nothing was found in 5. Of 66 the aneurysms (60 cases), 46 (43 cases) were treated by intrasaccule embolizotion with coils, 3 (3 cases) by occluding the parent artery with detachable balloon, 10 (10 cases) by surgery, and 1 (1 case) by combination of extracranial-intracranial bypass and balloon occlusion of parent artery. Six (3 cases) were not treated. Two aneurysms that could not be detected by 2D-Angio were diagnosed by 3D-Angio. Three aneurysms that were difficult or dangerous to embolize by 2D-Angio were embolized successfully with the help of 3D-Angio. Three aneurysms seemed to be embolized on 2D-Angio were proved impossible to be embolized on 3D-Angio. Of the 46 aneurysms embolized intrasaccularly, 38(82.6%) were completely embolized on 2D-Angio. In the 38, 8 had residual aneurysm on 3D-Angio. CONCLUSION: More accurate diagnosis and secure treatment of intracranial aneurysm can be reached by 3D-Angio. PMID- 11769596 TI - [Microsurgical treatment of 86 cases of intracranial aneurysms]. AB - OBJECTIVE: To summarize the microsurgical experience in the treatment of intracranial aneurysms. METHOD: The clinical materials, surgical modes and prognosis of 86 cases of clipped intracranial aneurysms were retrospectively reviewed. RESULTS: Of the 86 cases, 69 recovered, 10 were moderately disabled, 2 severely disabled, and 5 died. CONCLUSIONS: To avoid rerupture, aneurysms should be treated as soon as possible when the diagnosis was established. Proper management of rupture of aneurysms during operation is the key of success. Multiple aneurysms are better to be clipped in one stage. "de novo" aneurysms could be detected early by long-term angiography. PMID- 11769597 TI - [Microsurgical treatment of multiple intracranial aneurysms]. AB - OBJECTIVE: To summarize the experience in microsurgical treatment of multiple intracranial aneurysms. METHOD: Eight patients with 17 aneurysms were analysed retrospectively. RESULTS: Seven patients were followed up from 0.5 month to 10 years. According to Sundt's standard, the results in 5 patients were excellent and 2 good. One patients with bilateral PCom aneurysm died 1 week after operation. CONCLUSIONS: Multiple intracranial aneurysms should be removed as soon as possible, especially bilateral ones. The best way is first to clip the bled aneurysm and then the contralateral one by using coronal incision and bilateral pterional approach. This approach has the advantage of minimal invasion, good exposure, and less time-consuming. PMID- 11769598 TI - [Treatment of cerebral dural arteriovenous fistula targetting drainage vein or sinus]. AB - OBJECTIVE: To investigate the efficacy of occluding the drainage veins or sinus in patients with cerebral dural arteriovenous fistulae. METHODS: Twenty patients with cerebral dural arteriovenous fistulae involving cavernous sinus (8), transverse-sigmoid sinus (6), tentorial sinus (3), superior sagittal (1), Galen (1) and straight sinus (1), were treated by transvenous embolization (14 patients), surgical interruption of venous drainage (5) and sinus isolation (1) respectively. RESULTS: Clinical cure was obtained in 13 patients, symptoms were relieved in 6 and aggravated in one. Angiographically, complete cure was noted in 11 patients, partial disappearance of fistulas in 9. Sixteen patients were followed up for 1-48 months. CONCLUSION: Targetting drainage vein or sinus occlusion is effective and safe in the management of patients with cerebral dural arteriovenous fistulae. PMID- 11769599 TI - [Brain-stem cavernous hemangioma: surgical indications and approaches]. AB - OBJECTIVE: To evaluate the surgical indications and prognosis for cavernous hemangiomas (CHs) in the brain-stem. METHODS: From 1992 to 2000, 163 patients with intracranial CHs were operated on in our department. Among them, 14 patients (8 women and 6 men; mean age 42 years) had 15 CHs in the pons (12), mesencephalon (1) and medulla oblongata (1). Surgical indications for CHs are: progressive focal neurological deficits; hemorrhage; near the surface of the brainstem. Transvemian approach with midline suboccipital craniotomy was used for the lesions in the pons and medulla, near the floor of the IV cerebral ventricle. Transpetrosal approach was used for the lesions in the anterior part of the pons, and infratentorial supracerebellar approach for those in the mesencephalic case. RESULTS: CHs were totally removed from all the 15 lesions. Neurological deficits were improved in 10 patients after operation. Two patients had transient worsening of neurological conditions, which returned to the preoperative status during follow-up. The mesencephalic case, however had neurological condition deteriorated and was homebound after surgery. Pathologically, an oligodendroglioma was seen with CH in this case. CONCLUSIONS: If surgically indicated, CHs involving the brain-stem can be resected. Minimal invasiveness techniques and careful operative planning may contribute to the treatment of CHs involving the brain-stem. PMID- 11769600 TI - [Immunohistochemical study of vascular endothelial growth factor, relative receptors and ligands in vascular endothelial cells of cerebral arteriovenous malformation]. AB - OBJECTIVE: To study morphologically the formation, growth and rupture of cerebral arterivenous malformation (CAVM). METHOD: By means of immunostaining we studied vascular endothelial growth factor (VEGF), Tie-1, Tie-2, Ang-1, Ang-2 in endothelial cells (EC) of CAVM (30 specimens) and control cortical vessel (7 specimens) in the temporal lobe. RESULTS: The expression of VEGF in EC of CAVM was -884, +1,819, + +424 and in controls -445, +29, + +10. The expression of Tie 1 in EC of CAVM was -2,252, +626, + +12 and in controls -421, +88, + +6. The expression of Tie-2 in EC of CAVM was -683, +1,908, + 8 and in controls -444, +64, + +7. The expression of Ang-1 in EC of CAVM was -2,215, +209, + +41 and in controls -487, +41, + +9. The expression of Ang-2 in EC of CAVM was -956, +2,099, + +135 and in controls -475, , + +9. CONCLUSION: Up-regulated VEGF in part of brain and Tie-2, Ang-2 high expression in EC of some vessels may be one of major factors for CAVM formation growth, and rupture in the embryonic period. PMID- 11769601 TI - [Orthotopic liver transplantation: report of 70 cases]. AB - OBJECTIVES: To summarize the results of liver transplantation for various end stage liver diseases at Sun Yat-sen University of Medical Sciences, define the role of liver transplantation in treatment of hepatocellular carcinoma (HCC) and fulminant hepatitis B, and assess the value of lamivudine for preventing HBV recurrence. METHODS: Clinical data of seventy patients undergoing orthotopic liver transplantation (OLT) at Sun Yat-sen University of Medical Sciences between April 1993 and December 2000 were retrospectively analyzed. The main indications for liver transplantation were HCC (26 cases), liver cirrhosis (21), fulminant hepatitis B (12), sclerosing cholangitis (4) and other terminal liver diseases (7). Lamivudine was used in 12 patients with fulminant hepatitis B. Logistic multivariate regression analysis was employed to determine the risk factors predicting outcome of liver transplantation. RESULTS: Fifty-four patients survived for more than one month and 16 patients died within 30 days after OLT. The overall hospital survival rate was 77.1%. The hospital survival rates in Child's A and B patients were 87.5% and 83.3%, respectively. They were superior to those of the Child's C patients (P < 0.05). The outcome of patients with small HCC was superior to that of patients with large HCC. Preoperative APACE III scores, the severity of ascites, and serum creatine level had an independent influence on outcome. Of the patients with fulminant HBV infection, 9 survived for 2-24 months. Treatment with lamivudine monotherapy was both well tolerated and efficacious in patients with fulminant Hepatitis B. CONCLUSIONS: OLT can cure some patients and provide palliation for others with HCC. Patient selection is extremely important for predicting outcome. The results support the application of liver transplantation as a therapeutic modality for various end-stage liver diseases. Lamivudine is effective and safe in OLT for patients with HBV infection. PMID- 11769602 TI - [Cytomeglovirus infection after liver transplantation]. AB - OBJECTIVE: To study the prophylaxis, diagnosis and treatment of cytomegalovirus (CMV) infection after liver transplantation. METHODS: The clinical data of 10 patients receiving liver transplantation from July 1999 to October 2000 in our hospital were retrospectively analyzed along with literature review. RESULTS: CMV infection occurred asymptomatic cally in 6 patients, of whom, 5 were cured. CONCLUSIONS: Fluorogenic quantitative PCR (FQ-PCR) is effective, sensitive and highly specific for detecting CMV infection. It is important to monitor the status of CMV infection in patients receiving liver transplantation preoperatively and postoperatively. The key point for prophylaxis and treatment of CMV infection is early prevention and treatment after operation. Ganciclovir can exert significant therapeutic effects on CMV infection. PMID- 11769603 TI - [Early postoperative complications of choledochal cyst excision and reconstruction of biliary tract]. AB - OBJECTIVE: To study the early postoperative complications of choledochal cyst excision with reconstruction of the biliary tract. METHODS: In last 10 years, 173 patients aged from 27 days to 14 years (mean = 2.4 years) were operated on with procedures of choledochal cyst excision and biliary tract reconstruction by jejunointerposition between the liver hilum and duodenum or Roux-en-Y hepaticojejunostomy in our hospital. Amongst these 173 patients, 16 were found to suffer from postoperative complications. Therefore, their clinical data were retrospectively analyzed, and the prevention and treatment of the early postoperative complications discussed. RESULTS: The morbidity of early postoperative complications was 9.3% (16/173). The early complications included biliary leakage in 10 patients, wound dehiscence of abdominal wall in 3, hepatic failure in 1, pancreatic fistula in 1, and postoperative enteric intussusception in 1. The morbidity of early postoperative complications in infants younger than 1-year old was significantly higher than that in children(chi 2 = 15.78, P < 0.01). However, there was no significant difference in the morbidity of early postoperative complications between patients undergoing biliary tract reconstruction by jejunal segment interposition and those undergoing that by Roux en-Y hepaticojejunostomy (chi 2 = 0.07, P > 0.05). The total mortality in all the operated patients was 2.3% (4/173). Three patients died from biliary leakage and 1 from postoperative hepatic failure. CONCLUSIONS: Biliary leakage, wound dehiscence of abdominal wall and hepatic failure are major early postoperative complications. The morbidity in infants younger than 1-year old is higher than in children. The preoperative treatment of biliary tract infection, hypohepatia, and surgical skills during operation should be emphasized. Reoperation for biliary leakage should not be delayed and mycotic cholangitis after biliary leakage needs more attention. Tension suture in the fascial space of the abdominal wall is useful for the prevention and treatment of abdominal wall dehiscence. PMID- 11769604 TI - [Changes in serum neopterin levels in patients after trauma]. AB - OBJECTIVE: To evaluate the clinical significance of changes in serum neopterin levels in patients after trauma. METHODS: 41 patients with mechanical injury were divided into three groups according to the injury severity score (ISS). In all patients, blood collection was started within 24 h after injury, and blood samples were obtained at 3, 7, 14, and 21 d post-trauma. The relationship was determined between serum neopterin levels and ISS, multiple organ dysfunction syndrome (MODS) and prognosis in patients. RESULTS: Patients with ISS > or = 25 showed a high neopterin level compared with those with ISS < 16 (P < 0.05 or P < 0.01), and a correlation between mean neopterin levels and ISS was observed in severely injured patients (r = 0.518, P < 0.05). High neopterin levels were measured in patients who developed MODS, showing a persistent marked elevation from day 3 post-trauma onward. The difference between MODS and non-MODS patients was significant on days 3, 7, and 14 after acute insults (P < 0.05 or P < 0.01). In addition, serum neopterin levels of patients with fatal outcome were much higher than those of surviving patients, and it exceeded 50.0 nmol/L in most cases prior to termination (8/12 cases, 66.7%). CONCLUSIONS: Mechanical injury can cause a constant increase in neopterin level, implying an intact reaction by T lymphocytes and macrophage axis. The measurement of serum neopterin might serve as a tool for the evaluation of injury severity, early detection of MODS as well as prediction of outcome in patients after trauma. PMID- 11769605 TI - [Metabolic effects of medium-chain triglycerides in parenteral nutrition after surgery]. AB - OBJECTIVE: To investigate the difference between long-chain triglycerides (LCT) and medium-chain triglyceride (MCT). METHODS: Twenty-four surgical patients and 6 volunteers were studied. These subjects were randomly assigned to receive parenteral nutrition with MCT or LCT emulsion. Their arterial and venous concentrations were measured across the forearm. RESULTS: Muscle utilization was significantly improved with MCT administration. In fat clearance test, serum ketone concentrations were significantly higher in the MCT group than in the LCT group. The improvement in nitrogen retention may be associated with the increasing of ketone and insulin levels. CONCLUSIONS: Fat emulsions containing 50% MCT are safe for use in parenteral nutrition and provide an alternate fuel that improves protein metabolism. PMID- 11769606 TI - [Effect of lower androgen levels on arteriosclerosis]. AB - OBJECTIVE: To analyse the effect of lower androgen levels on risk factors for arteriosclerosis of men. METHODS: In 30 cases of primary prostate carcinoma (stage A), serum levels of testosterone (T), free testosterone (FT), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), prostatic specific antigen(PSA), triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apoprotein alpha 1 (APO alpha 1) and apoprotein beta(APO beta), insulin, plasma fibrinopeptide A (FPA), plasminogen activator inhibitor-1(PAI-1), fibrinogen were determined before and 1 week, 1,4,8 months after castration. RESULTS: T, FT, PSA decreased significantly 1 week after castration, and kept on decreasing afterwards. DHEA and SHBG were not changed. TG, fasting insulin and glucose, 2 hour insulin and glucose elevated significantly 1 month after castration. TG, LDL C, FPA and PAI-1 elevated 4 months after castration. Insulin sensitive index(ISI) decreased significantly 1 month after operation (-4.4 +/- 0.4 vs. -3.5 +/- 0.4, P < 0.01). HDL-C, APO alpha 1, APO beta and fibrinogen were not changed. There was a negative linear correlation between FT and TG, TC, LDL-C, PAI-1, FPA, fasting insulin and glucose, 2 h insulin and glucose, so did T. CONCLUSION: Lower androgen levels have adverse effect on lipid metabolism, coagulative function and insulin sensitivity, which are related to arteriosclerosis of men. PMID- 11769607 TI - [Expression of COX-2 in prostatic cancer and benign prostatic hyperplasia]. AB - OBJECTIVE: To investigate the expression of COX-2 in and benign prostatic hyperplasia and prostate cancer and its clinical implications. METHODS: Forty-two patients with and benign prostatic hyperplasia and 16 with prostate cancer were studied by immunohischemistry and western blot. RESULTS: Immunohischemiscal study showed positive results in 15 of the 16 patients and 11 of the 42 patients. Western blot showed that the expression of COX-2 was higher in prostate cancer than in and benign prostatic hyperplasia tissues(P < 0.01). CONCLUSION: Overexpression of COX-2 in prostate cancer may be related to the staging of prostate cancer. PMID- 11769608 TI - [Anterior thoracolumbar K-plate fixation system: design and clinical application]. AB - OBJECTIVES: To develop an anterior thoracolumbar K-plate fixation system and to report its preliminary clinical application. METHODS: The K-plate system was developed with titanium alloy(TC4, Ti6A14V) and self-locking screw design was used. In 23 cases treated with this system, 13 had thoracolumbar fracture, 9 tuberculosis, and back syndrome after lumbar TFC operation. RESULTS: All the 23 cases were followed up for one to ten months, averaging 4.5 months. In the 13 cases of fracture, body height of injured vertebra were regained completely, and neurologic deficits improved 2.1 grades in Frankel scale. In the 9 cases of tuberculosis, neurologic functions recovered and no local recurrence was noted. In one case of back syndrome, symptoms and signs did not occur after anterior TFC removal, interbody fusion, and K-plate fixation. This patient received second operation to remove K-plate 3 months after solid osseous fusion, and no electric erosion or obvious tissue reaction was found. 18 of the 23 cases were followed up for four months or more, and solid fusion was found in these patients in three to four months after surgery. No early complications related to implant were noted during the follow-up. CONCLUSION: This K-plate system is suitable for reconstruction of thoracolumbar stability after anterior decompression in indicated patients. PMID- 11769609 TI - [Microskin grafting in recent 15 years]. AB - OBJECTIVE: To summarize microskin grafting in recent 15 years. METHODS: Microskin grafting was performed in 162 patients with extensive burns. The indications and forms of the grafting, mechanization in making microsk in and outcome of wound recovered by micrografts were discussed. RESULTS: Extremely extensive third degree burns, common extensive third degree burns and extensive granulation wound were healed byn different ways of microskin grafting. A new machine was used to mince micrografts with good clinical results. The homografts as coverture was exfoliated in either necrosis or desquamation. Scar formation was related to wound repair. CONCLUSIONS: Microskin grafting has made progress in recent years. The orientation and even spread of micrografts are very important for good wound repair. The technic should be further improved. PMID- 11769610 TI - [Effect of calcium and temperature on adhesion of K-ras transformed rat lung cells]. AB - OBJECTIVE: To investigate the effect of calcium and temperature on cancerous cell adhesion. METHODS: K-ras transformed rat lung cells (KNRL cels) were used as experimental group, and normal rat lung cells (NRL cells) as normal control. The cells were cultured under the condition of implementation with Ca2+ and at 4 degrees C, 37 degrees C and 41 degrees C, and without Ca+2 at 37 degrees C. Cell adhesion and aggregation were examined. RESULTS: The average value of adhesive ability (Nt/N0) of KNRL cells was 0.81 +/- 0.15 at 37 degrees C, without CA2+ and 0.60 +/- 0.14, with Ca2+ (P = 0.041). The value was 0.53 +/- 0.12 at 41 degrees C, significantly lower than that at 37 degrees C (P = 0.046). CONCLUSION: Appropriate increase of Ca2+ and high temperature will strengthen the adhesive ability of tumor cells. PMID- 11769611 TI - [mRNA and protein expression of three growth-related factors and their possible signal transduction pathways in wound healing]. AB - OBJECTIVE: To observe the time course and tissue distribution of c-fos, c-myc and basic fibroblast growth factor(bFGF) genes and their proteins in burned skin, and explore the possible network regulation mechanisms of c-fos, c-myc and bFGF in wound healing and the role of the protein kinase C pathway involved in signal transduction among these growth-related factors. METHODS: The study was carried out on 188 Wistar rats. Animal model with 30% partial thickness scald injury was made and all rats were randomly divided into several groups: normal control (n = 8), injured control (n = 36), anti-c-fos (n = 36), bFGF (n = 36), 1-5 Isoquinolinyl-sulfony-2methylpiperazine (H7), and 2, 3-Butanedione monoxime (BDM) (n = 36). In situ hybridization, reverse transcription polymerase chain reaction (RT-PCR) and streptavidin peroxidase (SP) immunohistochemistry methods were used to detect the gene and protein expression of c-fos, c-myc and bFGF in the wounded tissues. RESULTS: (1) The first appeared induction of growth-related gene was c fos, the second bFGF, and the last c-myc. They were peaked at 3 h, 1 d and 3 d postburn with values of 14.5 +/- 1.3, t = 13.306; 0.15 +/- 0.04, t = 3.460 and 0.11 +/- 0.05, t = 2.292, respectively (P < 0.05). (2) Treatment with c-fos antibody decreased the expression of these three growth-related factors when compared with that in the controls. There were a 80% decrease in c-myc and a 85% decrease in bFGF. (3) Treatment with H7 inhibited the gene and protein expression of c-fos and bFGF. The peak times of c-myc gene and protein were delayed to 6 hours post injury. Treatment with BDM induced an earlier expression of c-myc mRNA at 6 hours, and increased the gene and protein expressions of c-fos and bFGF. The total amount of their values was increased to 0.23 +/- 0.07, t = 2.942 and 0.69 +/- 0.07, t = 5.134 (P < 0.01). CONCLUSIONS: Thermal injury can induce a series of growth-related gene expression showing a phasic control and regional distribution. c-fos plays an important role in wound healing process. Protein kinase C pathway may repair wound. PMID- 11769612 TI - [Antisense monocyte chemotactic protein-1 gene inhibits vein graft intimal hyperplasia in rabbits]. AB - OBJECTIVE: To identify the effect of in vivo local expression of recombine antisense MCP-1 gene on the development of vein graft neointima formation. METHODS: Jugular vein-to-artery bypass grafting was performed on 20 New Zealand white rabbits, of which 4 grafts were transferred with LNCX vectors, 6 grafts with antisense MCP-1 (200 micrograms) by cationic liposome, and 4 grafts as controls. Fourteen days after surgery grafts were harvested. The expression of antisense MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot. Grafts were processed for morphologic evaluation and immunohistochemistry analysis. RESULTS: Antisense MCP-1 was expressed in local gene delivery group, meanwhile MCP-1 expression in vein grafts was significantly inhibited (test group, 1.227 +/- 0.362; controls, 1.981 +/- 0.394, P < 0.05). Monocytes/macrophages adherence and infiltration were prominently reduced (test group, 24.3% +/- 2.7%; controls, 36.8% +/- 2.8%, P < 0.05), and intimal hyperplasia was markedly reduced [test group, (0.65 +/- 0.08) mm2; controls, 1.27 +/- 0.15) mm2, P < 0.05]. CONCLUSION: Local expression of antisense MCP-1 in vein graft significantly reduced intimal hyperplasia with inhibition of MCP-1 expression and prevention of monocytes/macrophages infiltration. PMID- 11769613 TI - [Effect of sepsis on the expression of ubiquitin and ubiquitinated protein in rat skeletal muscle]. AB - OBJECTIVE: To study the regularity of ubiquitin and ubiquitinated protein expression in rat skeletal muscle during sepsis, and the molecular mechanism of enhancement in skeletal muscle protein catabolism. METHODS: Wistar rats with sepsis were administered endotoxin peritoneally. The rats were randomly divided into 4 groups rats: 2, 6, 12 and 24 h after administration of endotoxin; each group (16) included normal controls. In vitro muscle incubation system with sufficient oxygen supply was used with amino acid automatic analyzer for detecting the proteolytic rate of the extensor digitorium longus(EDL) and soleus(SOL) muscle in the sample. The expression of ubiquitin and ubiquitinated protein in rat EDL muscle was determined by western blot. RESULTS: Total proteolytic rate in the EDL muscle increased slightly at 2 and 6 h after administering endotoxin into the peritoneal cavity, and no significant difference at 12 and 24 h was observed. There was a progressive increase of 155% and 220% in myofibrillar proteolytic rate at 2 and 6 h, and 40% at 12 h, respectively, as compared with that of the normal controls. The expression of ubiquitin and ubiquitinated protein in the EDL muscle rose by 46% and 2.4 fold at 2 h and 6 h after administering endotoxin, while the ubiquitinated protein of high molecular weight was determined. No significant changes were noted in the expression of ubiquitin and ubiquitinated protein at 12 and 24 h. CONCLUSION: The results indicate that activation of ubiquitin-proteasome pathway occurs in rat skeletal muscle during sepsis, and high expression of ubiquitin and ubiquitinated protein means that the substrate flowing into ubiquitin-proteasome pathway increases markedly, and then leads to muscle wasting. PMID- 11769614 TI - [Intraspinal implantation of genetically modified myoblasts with brain-derived neurotrophic factor gene in treating spinal cord injury in rats: neurophysiological study]. AB - OBJECTIVE: To observe the value of gene therapy to spinal cord injury in vivo by transferring gene of brain-derived neurotrophic factor (BDNF) to rat myoblast with retroviral vector electrophysiologically. METHODS: Transection of spinal cord at the level of T9 was produced in 30 adult SD rats that were divided randomly into three groups: BDNF gene modified myoblast implantation (group A), myoblast implantation (group B), and no cell implantation as controls (group C). Three months after operation, whether the axon had regenerated and how the neural function was restored were observed, using the techniques of cerebral somatosensory evoked potential (CSEP) and motor evoked potential (MEP). RESULTS: Three months after injury, 3 rats in group A showed CSEP signals and 5 rats MEP signals, but no electrophysiological response was found in group B or group C. The amplitudes of the recovery of CSEP or MEP signals decreased and their latencies increased as compared with those before injury. The neural function of the spinal cord was greater in group A than in B and C. CONCLUSION: Treatment with genetically modified myoblasts producing BDNF can accelerate recovery from traumatic spinal cord injury in adult rats. PMID- 11769615 TI - Changes for authors. PMID- 11769616 TI - An ethicist's commentary on the ethics of killing healthy animals. PMID- 11769617 TI - A retrospective study of neonatal mortality in farmed elk. AB - Despite the increasing importance of the Canadian elk industry, the veterinary literature concerning diseases of elk is sparse, in particular for the neonatal period. This study summarizes necropsy findings in 111 farmed elk calves, up to 30 days of age, submitted to the diagnostic laboratory of the Western College of Veterinary Medicine over a 9-year period (990 to 1998). Causes of mortality fit into 3 categories: infectious disease, noninfectious disease, and undetermined. Organisms causing disease included Escherichia coli, Listeria monocytogenes, and Cryptosporidium sp. Starvation, including dehydration, was also a significant cause of mortality. Necropsy records are a useful source of information, but their scope is limited. There is a need for research that determines the prevalence of neonatal elk diseases and identifies risk factors for morbidity and mortality. PMID- 11769618 TI - Comparison of analgesic techniques for antler removal in wapiti. AB - The purpose of this research was to compare the effectiveness of ring block anesthesia (LA) and electroanesthesia (A) for antler removal in elk given a long acting tranquilizer to remove stress from restraint. Thirty-two male wapiti were given 1 mg/kg body weight of zuclopenthixol acetate; the next day, they were restrained in a hydraulic chute, provided with electroanesthesia or a lidocaine ring block, and had their antlers removed. Behavioral response to antler removal was scored. Significantly more (P = 0.032) animals responded to antler removal in the EA group. Heart rates and arterial pressures were measured by a catheter connected to a physiological monitor. Heart rate increased significantly over time with EA, but not with LA. Heart rate increased from baseline significantly more in the EA group immediately prior to antler removal (P = 0.017), immediately post antler removal (P = 0.001), and at 1 min post antler removal (P = 0.037). It was concluded that EA is not as effective a method of anesthesia as is LA for antler removal. PMID- 11769619 TI - Outcome of limb amputations in wapiti: 13 cases (1995-2001). AB - The object of this investigation was to determine the outcome of limb amputation in wapiti. Medical records of 13 wapiti that underwent limb amputation were reviewed to determine age, weight, sex, injury preceding amputation, limb amputated, amputation location, length of hospital stay, complications, and outcome. Ages ranged from 3 months to 8 years and weights from 70 kg to 280 kg. All animals were female. Eleven animals sustained catastrophic long bone fractures prior to amputation. Five animals had front limb amputations and 8 had hind limb amputations. Of these animals, 1 with a front limb amputaiton and 5 with hind limb amputations survived. Postsurgical inability to stand is associated with hospitalization of > 1 day. Of the 13 wapiti reviewed, 5 with hind limb amputations have produced and reared offspring. Hind limb amputation can be considered a viable alternative to euthanasia when catastrophic orthopedic injuries occur in female wapiti. PMID- 11769620 TI - A simple procedure to secure an indwelling jugular vein catheter to the neck of cattle for repeated blood sampling. AB - A procedure to secure a jugular vein catheter system to the neck of cattle is described. A wide-mouthed polypropylene bottle attached to a halter strap provided a secure container for the catheter. This device allowed convenient access to the catheter for repeated sampling and, apparently, reduced discomfort to the cattle. PMID- 11769621 TI - Cervical stenotic myelopathy in a horse. AB - A 13-year-old, Thoroughbred gelding presented with a 3-year history of progressive ataxia of all 4 limbs. Physical and neurological examinations indicated a compressive lesion affecting the cervical spinal cord. Radiographs confirmed a lesion, and a myelogram a narrowing of the spinal canal at cervical vertebrae (6-7). Necropsy confirmed cervical stenotic myelopathy. PMID- 11769622 TI - Have you taken a critical second look? PMID- 11769623 TI - Fractures involving the distal extremity of the femur. Part 1--The immature patient. PMID- 11769624 TI - [Study on the effects of leptin on puberty development in children]. AB - OBJECTIVE: To study the effects of leptin on puberty development in children. METHODS: Three hundred obese and 300 healthy children without taking any medication or having evidence of endocrine or metabolic diseases were studied. Their ages of first spermatorrhea and menarche were surveyed, and blood levels of leptin, sex hormones, growth hormone (GH) and insulin (INS) were measured. RESULTS: With increased of age, blood levels of leptin appeared from low to high and from high to low again in the boys, with (1.04 +/- 0.21) nmol/L to (1.20 +/- 0.27) nmol/L and to (0.66 +/- 0.10) nmol/L in the obese group, and with (0.31 +/- 0.06) nmol/L to (0.45 +/- 0.10) nmol/L and to (0.19 +/- 0.04) nmol/L in the control group. While blood level of leptin appeared an increasing trend in girls, with (0.89 +/- 0.15) nmol/L to (1.39 +/- 0.23) nmol/L in the obese group, and (0.46 +/- 0.08) nmol/L to (0.88 +/- 0.18) nmol/L in the control group. Levels of sex hormones also appeared an increasing trend in the all groups. Levels of GH showed an abrupt increased at certain ages, different in boys from girls (14-15 years of age in boys and 13-14 in girls). In the all ages, serum levels of leptin and INS were higher in the obese group than those in the control group, while the level of GH was lower in the obese group than that in the control group. Serum level of leptin was higher in the obese group of both boys and girls than that in the control group, with (0.71 +/- 0.17) nmol/L and (0.30 +/- 0.04) nmol/L and (1.11 +/- 0.21) nmol/L and (0.70 +/- 0.18) nmol/L, respectively. Ages at first spermatorrhea and menarche were much earlier in the obese children than those in the controls, with (12.5 +/- 1.2) and (13.2 +/- 1.2) years of age in boys and (11.6 +/- 0.8) and (12.8 +/- 0.9) in the girls, respectively. Blood levels of leptin was higher in the girls than that in the boys. Age at menarche and earlier in the girls than that of first spermatorrhea in the boys. Blood level of testosterone correlated inversely with that of leptin in boys, while that of estradiol correlated with that of leptin in girls. Level of GH correlated inversely with that of leptin in boys and correlated with that in girls. Level of INS correlated with that of leptin in the control girls. CONCLUSIONS: Leptin might have an effect on initiation of puberty in children, possibly with more importance in girls than in boys. The gender difference in the degree of correlations between levels of leptin and GH may cause their difference in the ages at sudden growth in boys and girls. The gender difference in the degree of correlation between levels of leptin and sex hormone may cause their difference in the ages at first spermatorrhea and menarche in both boys and girls. PMID- 11769625 TI - [Relationship between gene polymorphism at the apolipoprotein E locus and serum lipid profile in urban children of school age in Beijing]. AB - OBJECTIVE: To study the relationship between gene polymorphism at the apolipoprotein E (ApoE) locus and serum lipid levels in children of school age. METHODS: Blood samples were collected from 307 normal children aged 7 to 11 years, including 150 boys and 157 girls, and their serum lipid profile, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein B(apoB), apoprotein A1 (ApoA I) and lipoptoein alpha[LP (alpha)], were detected and their ApoE-Hha I gene polymorphism were tested by the PCR-RFLP method. RESULTS: The detection rates for the most frequent genotype ApoE3/3 was 54.7%, other genotypes E4/3, E4/4, E3/2, E4/2 and E2/2 were 23.8%, 9.1%, 8.1%, 3.9% and 0.3%, respectively, in 307 children, with no significant difference between girls and boys(P > 0.05). Frequency of the often seen allele E3 was 70.7%, and that of E4 and E2 was 23.0% and 6.4, respectively, with E4 significantly higher than and E2 similar to that in the other domestic reports. The levels of TC, LDL-C, ApoA I and ApoB were higher in boys with genotypes E4/3 and E3/3 than those with genotypes E3/2 and E4/2. Levels of TC and ApoA I in the boys with genotype E3/2 were higher, with TC of 4.28 mmol/L and ApoA I of 3.41 mmol/L. There were no significant difference in serum lipid levels of girls with different genotypes(P > 0.05). There also was no significant difference in the ApoE-Hha I genotype distribution between normal children and those with high TC. ApoE2 could decrease the level of TC by 0.377 mmol/L, and LDL-C by 0.329 mmol/L. CONCLUSIONS: Serum level of TC associated with polymorphism of ApoE gene carrier in boys, with the lowest levels of TC, LDL-C and ApoE in three with allele E2. PMID- 11769626 TI - [Telomerase activity in lung cancer and adjacent peritumoral tissues determined by TRAP-SYBR green assay]. AB - OBJECTIVE: To develop methods for the qualitative analysis of telomerase activity by TRAP-SYBR Green assay and study telomerase activity in lung cancer and adjacent peritumoral tissues, and to explore the possible association with expression of P53. METHODS: Thirty six lung cancer tissues and 36 adjacent peritumoral tissues, 8 lung benign lesion tissues and A549 lung adenoma cell line, were examined for telomerase activity by TRAP-SYBR Green assay. The 36 lung cancer tissue samples were also examined for P53 protein expression by immunohistochemical staining. RESULTS: Telomerase activity in 5 cells of A549 lung cancer cell line was detected by TRAP-SYBR Green assay. Thirty of 36 (83.3%) lung cancer specimens, seven of 36 (19.4%) adjacent peritumoral tissues, three of 8 (37.5%) lung benign lesion tissues were positive for telomerase activity. Telomerase activity of lung cancer did not correlate with pathologic type, tumor size and clinical stage. P53 was over-expressed in 24 of the 30 (80%) lung cancer samples with telomerase activity. A significant correlation was found between telomerase activity and accumulation of P53 proteins (r = 00.60, P < 0.01). CONCLUSION: TRAP-SYBR Green assay may be a sensitive, fast and convenient method for qualitative analysis of telomerase activity, which is useful in diagnosis lung neoplasms. The relationship between telomerase activity and P53 accumulation needs further study. PMID- 11769627 TI - [Effects of selenium on hepatocellular protooncogene c-myc, c-fos and c-jun expression induced by cadmium in rats]. AB - OBJECTIVES: This study was conducted to explore effects of selenium on hepatocellular protooncogene c-myc, c-fos and c-jun expression induced by cadmium in rats. METHOD: Both cadmium and selenium were given to rats by i.p. and there were 5 SD rats in each group. Protooncogene c-myc, c-fos and c-jun expression in rat liver cells was measured with Northern Dot Hybridization. RESULTS: The results showed that cadmium chloride at doses of 5, 10 or 20 mumol/kg, significantly induced proto-oncogene c-myc, c-fos and c-jun expression, and when sodium selenite at the dose of 5 mumol/kg was given at the time, the effect of cadmium chloride on hepatocellular protooncogene c-myc, c-fos and c-jun expression was inhibited. CONCLUSION: Selenium at certain doses could inhibit hepatocellular protooncogene c-myc, c-fos and c-jun expression induced by cadmium in rats. PMID- 11769628 TI - [Effect of methylmercury chloride on the c-fos expression in brain nerve cells of the rats]. AB - OBJECTIVE: In order to study the mechanism of injury in the brain development caused by methylmercury chloride (MMC) and its effects on the c-fos expression in brain nerve cells of the rats with experiments in vitro and in vivo. METHODS: In vitro, the effect of MMC on c-fos expression in the cultured nerve cells was observed by immunocytochemistry(SP method). In vivo, Wistar pregnant rats were administered 4 mg MMC per kg of body weight by a gastric tube from the 7th to the 10th gastational days. On the 1st, 3rd, 5th, 7th, 10th and 15th days after birth, the rats were killed and tissue sections were prepared from their brain, respectively. The expression of c-fos was detected by SP method. RESULTS: The percentage of c-Fos-positive neuron in rats brain began to increase at 0.5 hours after being cultured in in vitro with 0.3 mumol/L MMC continuously, and increased gradually as length of the exposure to MMC prolonged. The percentage of c-Fos positive of cultured nerve cells in vitro were (6.97 +/- 2.86)%, (66.86 +/- 5.32)% and (64.49 +/- 3.09)% in the experimental groups exposed to MMC for 10 min, 2 h and 6 h, respectively. In vivo, the percentage of Fos-positive neuron nuclei decreased with development of neonatal rats. The percentage of c-Fos positive neuron in the experimental groups was higher than that in the control groups and decreased with length of development. The percentages of c-Fos positive neuron were (47.01 +/- 3.79)% and (46.71 +/- 1.96)% in the experimental group 1 and 3 d, and (35.8 +/- 3.04)% and (33.35 +/- 1.06)% in the control group, respectively, with very significant difference. CONCLUSIONS: It is concluded that MMC could induce c-fos over-expression in the nerve cells of the rat brain, which could explain the mechanism of injury to brain development caused by MMC. PMID- 11769629 TI - [Classification study on the marshland in endemic areas of Schistosoma japonicum using satellite TM image data]. AB - OBJECTIVE: To create a land cover map of the marshland region of Schistosoma Japonicum using satellite TM data from Chayegang, Jiangxi Province. METHODS: Satellite data of three TM bands, namely TM3, TM4 and TM5, were selected to be used in classification study with Principal Components Analysis. Then TM satellite images were applied to false color composite and unsupervised classification with computer software to manage the TM data. Finally the resulting clusters were identified by undertaking site visits and a systematic sampling snail survey was also carried out in the study area in April, 2000. RESULTS: Three land cover classes were generated, including class 1, the carex zone that is both the dominant vegetation and main snail habitats of the study area. Based on the snail survey in the spring of 2000, the live snail density and infectious snail density of the carex zone were 2.51/0.11 m2 and 0.006 9/0.11 m2, respectively. The infection rate of the snail was 0.28%. No snail was found in land cover class 3, the mixed vegetation, because the altitude of this area is either above 17 m or under 14 m and therefore the vegetation in this area is unsuitable for snails to survive. CONCLUSION: Remote sensing can contribute the study on the distribution of snail habitats and become a promising epidemiological study method for schistosomiasis and other ecological diseases. PMID- 11769630 TI - [Development of a diagnostic kit of enzyme-linked immunoassay for detecting serum anti-hepatitis E virus IgG]. AB - OBJECTIVE: To develop a diagnostic kit for detecting serum anti-hepatitis E virus (HEV) IgG with enzyme-linked immunoassay (ELISA). METHODS: The diagnostic kit of detecting anti-HEV IgG with ELISA was prepared by two synthetic HEV peptides used for coating the solid-phase to capture the antibody against HEV in serum, and then by horseradish peroxidase antihuman IgG (gamma chain) added as the second antibody to bind the anti-HEV IgG in serum. Its sensitivity, specificity, precision and stability were measured and clinically evaluated. RESULTS: The sensitivity, specificity, and precision of the diagnostic kit detected by the China National Institute for the Control of Pharmaceutical and Biological Products were 90% (1/10), 100% (0/30) and < 15%, respectively, meeting the national standards for detecting serum anti-HEV IgG with ELISA. The ELISA Kit is stable for 1 year at least under 4 degrees C. The total consistency rates were 100% (43/43) and 96.6% (86/89), as compared with Genelabs and Singaporean DBL kits. This diagnostic kit for detecting serum anti-HEV IgG with ELISA was evaluated and approved by the State Drug Administration, China and a certificate was conferred in 1998. CONCLUSIONS: The diagnostic kit for detecting anti-HEV IgG with ELISA can be used for epidemiological studies and clinical diagnosis of HEV infection. PMID- 11769631 TI - [Effect of soybean protein and high calcium intake on the concentration of serum lipids in hypercholesterolemic rats]. AB - OBJECTIVE: To investigate the effects of dietary soybean protein or/and high calcium intake on the concentration of serum total cholesterol (TC) and serum lipids in hypercholesterolemic rats. METHODS: Following 14 days of inducing the hypercholesterolemia model successfully, 24 female rats were fed 4 experimental diets contained 20% of protein each from either casein or soybean protein and either a normal or high concentration of calcium (0.59% and 1.12%) in a 2 x 2 factorial design. RESULTS: After the experimental diets had been fed for 21 days, TC was (10.56 +/- 2.74, 7.99 +/- 2.19, 5.48 +/- 0.51 and 6.81 +/- 0.98) mmol/L in the rats fed diets containing casein and normal concentration of calcium, casein and high concentration of calcium, soybean, protein and normal concentration of calcium, and soybean protein and high concentration of calcium, respectively. According, Serum apolipoprotein B100(ApoB100) was (0.46 +/- 0.14, 0.31 +/- 0.12, 0.17 +/- 0.07, and 0.21 +/- 0.05) g/L, respectively. Comparing with the rats in casein group, the TC and ApoB100 of the rats in other 3 groups were significantly low (P < 0.05). Whereas, the changes of TG and HDL-C were not significant in these rats. CONCLUSIONS: Dietary soybean protein or/and high calcium intake lower TC in hypercholesterolemic rats and there is an interactive effect of these two dietary factors on lowering TC. Further researches are needed for explaining the possible mechanism of soybean protein and high calcium intake on lowering TC. PMID- 11769632 TI - [Evaluation of historical exposure to silica dust for the workers employed in geologic exploration industry]. AB - OBJECTIVE: To evaluate their level of exposure to silica dust in the workers employed in geologic exploration industry using a quantitative method. METHODS: Monitoring data of exposure to silica dust since 1950s were collected for the workers in various jobs from the factories and mines of the bureaux of geological exploration in the nine provinces, with 30,000 pieces of figures in total. Job title and history of employment were determined for 1,627 employees. Levels of exposure to silica dust in various factories and mines were estimated based on the data mentioned-above, including amount of respirable dust, total dust in the lungs, and proportion of free silica dust to the total silica dust. RESULTS: Concentration of total silica dust was 14 mg/m3 in average in the factories and mines, with a range of 29 mg/m3 during the earlier years to 3 mg/m3 in recent years, and that of respirable silica dust was 3 mg/m3, in average, with (28.0 +/- 8.2)% of free silica dust. Different indices of exposure to silica dust were calculated for individuals, based on their history of employment and level of exposure. CONCLUSION: Assessment of exposure to silica dust during the past years, based on the monitoring data, could provide basis for evaluation of dose response relationship. PMID- 11769633 TI - [Changes of serum transferrin receptor in children with iron deficiency and its response to iron supplementation]. AB - OBJECTIVES: To study the level of serum transferrin receptor (sTfR) in children with different stages of iron deficiency, as well as in the normal children, to observe its response to iron supplementation, and to explore the role of sTfR in surveillance of iron status and assessment of iron supplementation in population. METHODS: By determining iron status index, 1,006 children aged 6-14 years in Fangshan District, Beijing were divided into four groups, control group, iron depletion (ID) group, iron deficiency erythropoiesis (IDE) group and iron deficiency anemia (IDA) group, and 239 of them were measured for sTfR with Quintikine enzyme immunoassay (R&D system, Minneapolis, MN) and sTfR/logserum ferratin (SF) was estimated. Iron supplementation (NaFeEDTA capsules, containing 60 mg iron element per capsule) was administered for the children with ID and IDE per capsule once weekly and for the children with IDA per capsule thrice weekly for nine weeks. Iron status index and sTfR were measured before and after iron supplementation. RESULTS: The levels of sTfR and sTfR/log SF in children with ID, IDE and IDA were (20.03 +/- 2.33) nmol/L, (24.52 +/- 1.07) nmol/L, (33.28 +/- 6.09) nmol/L and (18.15 +/- 5.31), (20.98 +/- 8.88), (29.08 +/- 8.57), respectively, significantly higher than those in the control group [sTfR(18.74 +/ 3.06) nmol/L and sTfR/log SF(9.89 +/- 1.74)]. Statistical analysis showed that sTfR correlated to free erythrocyte protoporphyrin and hemoglobin. sTfR levels in normal children was (12.5-23.5) nmol/L. After iron supplementation, sTfR levels in children with ID was (16.37 +/- 3.10) nmol/L, significantly decreased than those before iron supplementation, but no change in sTfR was observed in children with IDE and IDA. sTfR/log SF were decreased significantly in all children with ID group(11.42 +/- 3.12), IDE (16.54 +/- 4.70) and IDA (23.59 +/- 9.93). CONCLUSION: sTfR is a specific indicator for identifying IDE and IDA, and sTfR/log SF is a sensitive index for assessing the effects of iron supplementation. PMID- 11769634 TI - [A randomized, double-blind, placebo-controlled, multicenter study on sibutramine in over-weighted and obese subjects]. AB - OBJECTIVES: To assess weight loss efficacy, safety and tolerability of sibutramine in simple obese subjects. METHODS: Randomized, double-blind, placebo controlled clinical trial. Four hospital outpatient clinics in Shanghai, Chongqing, Shandong and Tianjin, respectively. PARTICIPANTS: 233 men and women, 18-65 years old, with body mass index (BMI) ranging from 27 to 40 kg/m2 were randomly divided into an intervened group and a placebo control group. Sibutramine 10 mg or placebo once a day. MAIN OUTCOME MEASURES: Body weight, routine laboratory and clinical safety monitoring. RESULTS: Of 233 eligible patients, 120 received sibutramine and 113 placebo. Weight reduction was significantly greater in the intervented group (6.8 +/- 3.1) kg than the placebo control group (0.48 +/- 2.6) kg from week 4 onwards to week 24 (P < 0.001). Some minor side effects were noticed in the subjects who took sibutramine. But the symptoms were light and short term. Sibutramine was well tolerated. CONCLUSIONS: Sibutramine 10 mg once a day is an effective and safe therapy for weight reduction in simple over-weighted and obese subjects. PMID- 11769635 TI - [Association of beta 3-adrenergic receptor gene with obesity in patients with type 2 diabetes mellitus]. AB - OBJECTIVE: To investigate the association between the mutation of beta 3 adrenergoc receptor gene and obesity in patients with type 2 diabetes. METHODS: Body mass, waist-hip ratio, blood pressure and blood lipids were measured in 154 type 2 diabetic patients. Polymerase chain reaction and the restriction fragment length polymorphism analysis were used to determine the wild, heterozygous and homozygous forms of beta 3-adrenergoc receptor gene. RESULTS: The frequency of the Trp64Arg mutation was 42.5% and the frequency of Arg64 allele was 22.6%. The mutation frequency of the genetic types was significantly different between the obese and non-obese type 2 diabetes mellitus patients. The body mass, systolic blood pressure, diastolic blood pressure, HDL-cholesterol were significantly different, when those with Trp64Arg heterozygous were compared with those with Trp64 homozygous. CONCLUSIONS: The genetic mutation of beta 3-adrenegoc receptor in patients with type 2 diabetes is probably related to obesity. PMID- 11769636 TI - [Studies on fatty liver, blood glucose and related factors in simple obese children]. AB - OBJECTIVE: To study the prevalence of fatty liver, blood glucose and related factors in simple obese children. METHODS: Their liver was scanned with B-type ultrasound and fasting blood glucose (with a microassay glucometer), as well as other related morphological and functional indices, were measured in 62 children aged 8 to 11 years, including 32 obese ones and 30 control ones. RESULTS: Prevalence of fatty liver in obese and control groups was 93.8% and 10%, respectively, with very statistically significant difference (P < 0.01). Blood glucose level in obese and control groups was 5.42 mmol/L and 5.54 mmol/L, respectively, with statistically significant difference (P < 0.05). Proportion of children with normal cardiac function was 62.5% and 93.3%, respectively, in obese and control groups, with significant difference (P < 0.05). The prevalence of fatty liver correlated positively with skin-fold thickness, waist to hip ratio (WHR) and body mass index (BMI), with coefficients of correlation of 0.8786, 0.6256 and 0.8454, respectively (P < 0.01). Blood glucose correlated with skin fold thickness and BMI positively, with coefficients of correlation of 0.3403 and 0.3155, respectively (P < 0.05). Regression analysis showed that skin-fold thickness and WHR were major risk factor for fatty liver and skin-fold thickness was major risk factor for high blood glucose. CONCLUSIONS: Simple obesity could cause damage to the liver, glucose metabolism and cardiac function in children, forming the potential risk factors for cardiovascular diseases, diabetes and disturbance of lipid metabolism in adults. PMID- 11769637 TI - [Study on anti-HBV effects by antisense oligodeoxynucleotides in vitro]. AB - OBJECTIVE: To study the inhibition effect of anti-HIV oligodeoxy-nucleotides on HBV X gene. METHODS: Three antisense phosphorothioate oligodeoxy nucleotides(AsON) complementary to the initiator of X, DR2, EN II respectively, were synthesized and tested for their anti-HBV activity on HepG2.2.15 cells with ELISA methods. RESULTS: When the best effect concentration of AsON was 10 mumol/L, the inhibition rates on HBsAg of three AsON were 57%, 60% and 52% respectively, and on HBeAg were 56%, 45% and 56% respectively. There were two inhibition peaks at different times. There was no inhibition effect treated by random control (< 12%). Using the 3-(4,5-dimethythiazol-xyl)-2,5-diphnyl tetrazolium bromide method, there was no cytotoxicity at 40 mumol/L of AsON. CONCLUSION: AsONs on three key region of X gene were effective drugs to inhibit the expression of HBV. PMID- 11769638 TI - [Experiment observations of the germicidal effects of disinfectants on Vibro cholerae of El Tor biotype in different water bodies]. AB - OBJECTIVE: To study the germicidal effect of disinfectant on vibro cholerae of El Tor biotype in different water bodies and to set a guidelines for disinfection in the epidemic foci of cholera. METHODS: The suspension quantitative bactericidal test was used to examine the germicidal effects of four kinds of disinfectants, including Chlorine compound disinfectant, Indophor, Chlorine dioxide and Glutarldehyde, on vibro cholerae of El Tor biotype in waste water from residential areas and hospitals, and water from ditches, rivers and seas. RESULTS: When germicidal rate for Vibrio Cholerae of El-Tor biotype in the five different kinds of water bodies reached to 100% in five minutes, concentrations of Chlorine compound disinfectant, Indophor, Chlorine dioxide and Glutaraldehyde were 25.0-250.0 mg/L, 100.0-250.0 mg/L, 10.0-25.0 mg/L and 100-500 mg/L, respectively. CONCLUSIONS: Germicidal effects of the four kinds of disinfectants on Vibrio Cholerae of El-Tor biotype differed, and so did germicidal effect of each of the same disinfectant on it in the five different kinds of water bodies. Concentrations of disinfectants needed to disinfected waste water was higher than that to disinfect natural water. PMID- 11769639 TI - [Adverse effects of exposure to p-nonylphenol on reproductive system of young male rats]. AB - OBJECTIVE: To study the adverse effects of exposure to p-nonylphenol (NP) during gestation and lactation on the reproductive system of young male rats. METHODS: Pregnant rats were administrated with p-nonylphenol, at doses of 0, 50, 100 [symbol: see text] 200 mg/kg of body weight, respectively, by gavage from the first day of gestation to the day of weaning, i.e., the 21st day after birth. The young male rats were killed at the age of 70 days and some indices related to their reproductive system (i.e., weight of the gonad, sperm counts of the epididymis, histology of the testes, et al.) were analyzed. RESULT: Weights of the testes and prostate gland decreased with the increase doses of exposed NP, their weights of the testes of 2.86, 2.98, 2.59 and 2.44 g, and those of the prostrate gland of 0.26, 0.23, 0.20 and 0.19 g, respectively. The same trend existed in daily production of sperm in the testes and sperm counts of the epididymis, with 22.46, 18.46, 17.43 and 17.26 x 10(6) sperm per gram of the testis, with sperm counts of 46.85, 39.74, 35.57 and 31.36 x 10(6) per gram of the epididymis tail. Separation of prepuce occurred on the 47.83th days and 46.31th days in the rats exposed to 200 mg/kg of NP and in the control group, respectively. CONCLUSION: NP could decrease their ability of spermatogenesis in the rats without morphological changes of spermatogenic cells of the testes and epididymis. PMID- 11769640 TI - [Advance of dental implantation in China]. PMID- 11769641 TI - [Review and prospects of dental implantation in China]. PMID- 11769642 TI - [The mandibular molar-area implantation of screw-typed dental implants]. AB - OBJECTIVE: To study molar area implantation with screw-typed implant based on the specific anatomic properties of inferior alveolar nerve. METHODS: Depending on the degree of alveolar atrophy in mandibular molar area, the direct implantation, the buccal-to mandibular-canal implantation, and the repositioning inferior alveolar-nerve implantation were employed. During the period of 1992 to 1998, a total of 22 cases of this kind with 45 dental implants were restored. The follow up period was 5 years. RESULTS: 2 dental implants were lost respectively after 3 months of insertion and after 1 year of restoration. All the 43 others, however, still remained complete osseointegration, with no obvious crestal bone rebesorption and with excellent function. The 5-year accumulating survival rate of dental implants was 96%. CONCLUSIONS: These three surgical techniques, to a large extent, can solve the problems of mandibular molar area implantation. The key to success of each technique is the selection of patient and the selection of surgical project. PMID- 11769643 TI - [The application of three-dimensional model in the oral and maxillofacial surgery]. AB - OBJECTIVE: To exploit the three-dimensional model technique and apply it in the oral and maxillofacial surgery. METHODS: Using CT and rapid prototype technique to make three-dimentional model and used it for the therapy of the comminuted zygomatic features, jaw bone asymmetry, defects after tumor removal, and implantations. RESULTS: By using three-dimensional models eight patients with comprehensive bone defects had good results. CONCLUSIONS: Three-dimensional models can help surgeons in many ways for the therapy of the oral and maxillofacial deformities. PMID- 11769644 TI - [The experiment of pegylated liposomal doxorubicin to therapy tongue cancer and metastases lymph nodes]. AB - OBJECTIVE: To investigate the effects of pegylated liposmal doxorubicin (PLD) in treating animal model of tongue cancer. METHODS: The tongue cancer model was established in 70 goldn hamsters, and PLD was injected. The free doxorubicin and its concentration in circulating blood and lymph nodes, the weight of animals, volume of tumor, were defected. RESULTS: Tumor inhibition effect of the PLD group was higher than controls. CONCLUSIONS: PLD can be regarded as a valuable drug system to treat oral cancer. PMID- 11769645 TI - [The effect of the hyper-erupted third molar on chewing movement]. AB - OBJECTIVE: To investigate the effect of the hyper-erupted third molar contacting closely to the distal surface of the opposing second molar on the chewing movement. METHODS: Twenty-three university student volunteers, 11 with hyper erupted third molar teeth and 12 with normal occlusion, were enrolled in present study. There were totally 6 unilateral hyper-erupted third molars (3 upper and 3 lower) and 5 bilateral hyper-erupted third molars (1 bilateral upper and 4 bilateral lower). No other significantly abnormal occlusal phenomenon was observed. Five gum-chewing cycles masticated with an each side were separately recorded by means of K6-I mandibular kinesiograph (MKG) and the chewing cycles were analyzed. Both three-dimensional amplitudes and the related velocities were automatically documented with the instrument. RESULTS: (1) The chewing graphs recorded on both frontal and horizontal planes in controls were typically smooth cycles with clearly occlusal phase tracings. On the sagital plane the opening and closing traces around intercuspal position (ICP) were usually overlapped with each other. (2) 63.6% frontal cycles of the subjects with hyper-erupted third molar had an obvious table (0.2 mm to 1.0 mm in width) around ICP, 50% horizontal cycles of the subjects had a 0.2 mm to 0.5 mm step near to ICP, 72.7% opening and closing traces on the sagital plane separated into anterior and posterior branches. The abnormal traces on the three different planes of the hyper-erupted third molar tooth group appeared to be related each other, implying that they might be caused by the same characteristics of occlusion, namely, the hyper erupted third molar. (3) Subjects with hyper-erupted third molar masticated in more posterior direction, together with a higher chewing terminal velocity. CONCLUSIONS: The hyper-erupted third molar had a significant effect on the chewing cycles around ICP, as well as on the amplitude and velocity of chewing movement. PMID- 11769646 TI - [Interleukin-1 increase nitric oxide synthesis through up-regulation of inducible nitric-oxide synthase by rabbit mandibular condylar cartilage cells in vitro]. AB - OBJECTIVE: To investigate the influence of IL-1 on the biosynthesis of nitric oxide by rabbit mandibular condylar cartilage (MCC) cells. METHODS: MCC cells of white rabbits were harvested enzymatically and cultured in DMEM supplemented with 0.4% newborn calf serum. In the experiment, a variety of concentrations of IL-1 were added to the medium. NO production was determined as nitrite accumulation in the medium. The effects of IL-1 on the mRNA levels of inducible nitric-oxide synthase (iNOS) were assessed by mRNA in situ hybridization method. RESULTS: IL-1 can significantly increase nitric oxide synthesis by MCC cells in a concentration dependent manner. In addition, normal MCC cells had light expression of iNOS expression and IL-1 (10-100 micrograms/L) promoted the expression of iNOS. CONCLUSIONS: IL-1 can inhibit the chondrocytes proliferation and induce apoptosis that might be through the way of up-regulation of iNOS expression. PMID- 11769647 TI - [The effect of mouthguard on strength of the musculus deltoideus]. AB - OBJECTIVE: To investigate the effect of mouthguard on strength of musculus deltoideus and to observe the possibility of its improving sports ability. METHODS: The custom mouthguards were fabricated respectively for 8 subjects with soft resin by direct method. The activities of the musculus deltoideus and masseter were tested by means of electromyograph (EMG), while the subjects lay, made maximum voluntary biting with mouthguard and pressed 5 kg. The EMG potentials were transferred to a computer. The data were handled and the integral values of EMG were exported. RESULTS: The subjects set a great value on the mouthguard's comfort, retention and protection. The EMG values of the musculus deltoideus and masseter of the subjects biting with mouthguards were 1.1600 v/s and 0.3825 v/s, and the values of those biting without mouthguards were 0.6125 v/s and 0.213 8 v/s, respectively. The muscular strength of the former was significantly improved compared with that of the latter (P < 0.01). CONCLUSIONS: Wearing a mouthguard and maximum voluntary biting can enhance the masseter force and reflectively improve the musculus deltoideus strength. PMID- 11769648 TI - [Study on anodic oxidation and hydrothermal treatment of titanium implants with thin hydroxyapatite layers: an implantational test in rabbits]. AB - OBJECTIVE: To learn bone response to commercially pure titanium implants with anodic oxidation followed by hydrothermal treatment in vivo. METHODS: Tweleve rabbits were averagely divided into three groups. And 36 implants (9 polished, 9 roughened by grit-blasting, 9 treated with anodic oxidation followed by heat treatment and 9 treated with anodic oxidation followed by hydrothermal treatment) were randomly implanted into femur bones of each group rabbits. Implants were harvested at 4 W, 8 W and 16 W respectively. Slice about 30 microns thick were ground with a grinding machine and stained with 1% toluidine blue. The bone implant interface was observed with light microscopy and scanning electron microscopy. Implant surface element contents were also detected with EDAX. RESULTS: Woven bone rapidly transferred to lamellae bone at 8 weeks for anodic oxidized implants followed by hydrothermal treatment, which appeared little woven bone and no hydroxyapatite debris between the interfacial zone at 16 weeks. In addition, Ca and P contents increased much more for hydrothermal treated implants after implantation compared with polished implants. CONCLUSIONS: Anodic oxidation followed with hydrothermal treatment of a titanium fixture could speed up woven bone transferring the lamellae bone at early time of implantation, which meant thin HA layers could accelerate bone healing at the implanted site and might shorten healing time. This superiority need more research in the future. PMID- 11769649 TI - [Effects of Streptococcus sanguis on blood composition, blood pressure and cardiac dysfunction in rabbis]. AB - OBJECTIVE: To investigate effect of streptococcus sanguis on blood cell and cardiopulmonary changes. METHODS: 133-79 strains of streptococcus sanguis (aggregation positive) were infused intravenously into rabbits. Before and 5, 10, 20, 30, 45, 60 min after infuse platelets count, leukocytes count, blood pressure and ECG were measured. RESULTS: After infused intravenously, both platelets and leukocytes count decreased remarkably (P < 0.01, n = 12). The ECG showed ST segment depression (> 0.06 mV). Diphasic blood pressure occurred (first hypertensive then hypotensive). CONCLUSIONS: Streptococcus sanguis 133-79 strains in circulation system might cause myocardia ischemia, blood pressure changes, peripheral circulation platelets and leukocytes decrease remarkably. PMID- 11769650 TI - [The change of immunocompetent cells in normal human dental pulp during development of immature permanent teeth]. AB - OBJECTIVE: To study changes of several immunocompetent cells (ICCs), namely, pulpal dendritic cells (PDCs), T lymphocytes, B lymphocytes, and endothelial cells, in normal human dental pulp according to different development stage of completely erupted but not fully developed premolar in order to provide evidence for local immune defense mechanisms during development of immature permanent teeth. METHODS: Based on the dental development status, the pulp tissue was classified into the following groups: big trumped-shaped group, small trumped shaped group and closed group. The above mentioned cells were immunohistochemically examined by use of HLA-DR, CD45RO, CD20 mouse anti-human monoclonal antibodies. Double-staining was also done by use of the former two antibodies. The number of positively stained cells or blood vessels was counted and statistically analyzed. RESULTS: 1. Normal dental tissue of three groups all expressed HLA-DR+ PDCs. Among three groups, the number of HLA-DR+ cells in big trumped-shaped group was more than that of small trumped-shaped group and closed group. 2. There was no significant difference of positive blood vessel rate of HLA-DR expressing endothelial cells among three groups. 3. There was no significant difference of CD45RO+ T cells among three groups. 4. By use of double labeling immunohistochemistry, HLA-DR+ PDCs and CD45RO+ T cells were found to be rarely in contact with each other. Correlation analysis between two kinds of cells did not indicate the linear relationship. CONCLUSIONS: The number of PDCs tends to decrease with increasing age in the developing dental pulp of human normal tooth, other ICCs are not related with dental development. PMID- 11769651 TI - [A qualititative study on p16 mutiple tumor suppressor gene, ras oncogene p21 and DNA content in parotid tumor and its' contiguous acini]. AB - OBJECTIVE: To determine the biologic characteristics of tumor's contiguous acini and the relationship of recurrence or malignant transformation. METHODS: With the use of immunohistochemistry and flow cytometry, the features of p16, p21 and DNA expression in 68 tumors and their contiguous acini were studied. RESULTS: The expression of p16 and p21 gene were found in tumors that the possitive unit (PU) was higher than normal acini (P < 0.01). The areas of expression were mainly located in cytoplasm of gland duct cells. Strong possitives or weak possitives could be observed in the tissues of malignant tumors and their contiguous acini respectively, as well as the PU in the deep lobe of recurrent parotid tumors in which the capsule was incomplete was higher than that in the superficial lobe of primary parotid tumors with complete capsule (P < 0.05). Futhermoer the levels of DI, S% and PI were higher in perotid tumors and its contiguous acini than normal acini (P < 0.05). CONCLUSIONS: When p16 multiple tumor suppressor gene is lost and oncogene p21 is mutated, the tumor's contiguous acini maybe in the condition of "paraneoplasm" after parotid tumor removal, and it has a strong ability of preliferation, which play an important role in recurrent or malignant change of the parotid tumor. PMID- 11769652 TI - [Analysis of relationship between risk factors of malignant transformation of oral leukoplakia and the LSCP system]. AB - OBJECTIVE: To explore the clinical significance of the LSCP (lesion size, site of lesion, clinical aspects, pathological aspects) classification and staging system through a comprehensive analysis of relationships between the risk factors of malignant transformation of 209 cases with oral leukoplakia and the LSCP classification and staging system. METHODS: Single factor Chi-square test was first performed to examine the associations between LSCP stages (I, II, III, IV) of oral leukoplakia and each of risk factors, including sex, site, size, numbers of lesion, alcohol and tobacco consumption, clinical classification and histopathological classification respectively, to select the most significant factors which influence the LSCP classification and staging. Then, the association of these selected factors with LSCP stages of oral leukoplakia (stage IV vs. I, II and III) was evaluated using multiple logistic regression analysis. RESULTS: Sex, site of lesions, clinical aspect and histopathological features of lesions were chosen as risk factors incorporated into the multiple logistic regression models. The results demonstrated that the risk of oral leukoplakia of the female patients classified as LSCP stage IV was 2.49 times as high as that of the male patients. The risk of lesions occurring in tongue and/or that floor of mouth was higher than that in other sites. Among the different clinical subtypes of lesions, the verrucous leukoplakia was the highest and 10.00 times as high as that of the homogeneous one. Among the different histopathological types, when hyperplasia and mild dysplasia were set as the basic level, the risk of severe dysplasia classified as LSCP stage IV was the highest and 499.55 times as high as the basic level, while that of moderate dysplasia was 276.48 times as high as the basic level. Pathological features with moderate and severe dysplasia were the most important contributory factors to the LSCP staging. CONCLUSIONS: The LSCP classification and staging system provides a comprehensive description of the features of oral leukoplakia, which is helpful in evaluating the overall risk of malignant transformation of oral lesion, and is valuable in clinical follow-up and developing the best treatment plan. PMID- 11769653 TI - [Analysis of mandibular position of patients with angles Class I and Class II, division 1 malocclusion]. AB - OBJECTIVE: To study changes of condyle position and occlusion between centric jaw relation and maximum intercuspation positions. METHODS: The power centric registration advocated by Roth was used to take centric relation bite registration for 50 patients (25 Class I and 25 Class II, Division 1) and diagnostic models were mounted and analysed with Panadent articulator and condyle position indicator. RESULTS: Nearly all patients had CR-MI differences in all three planes of space. 70% of the sagittal displacement was within 2.0 mm and 87% of the transverse displacement was within 1.0 mm. Most of the condyles moved posteriorly and inferiorly. 65% of the initial contacts in CR occured on the most posterior molar on single side. Correlation was found between some variables of condylar displacement and occlusion changes. No significant difference was observed in condylar position and occlusion changes between Class I and Class II, Dvision 1 patients. CONCLUSIONS: The occlusion in centric jaw relation should be analysed before treatment to reveal the disharmony between occlusion and jaw position. PMID- 11769654 TI - [Surgical correction of hemimandibular hyperplasia]. AB - OBJECTIVE: Evaluate the surgical corrective result of hemimandibular hyperplasia. METHODS: 33 patients were treated by orthognathic surgical procedures. The affected condyles of all patients were removed. RESULTS: The surgical corrective result of all patients was satisfactory. CONCLUSIONS: The deformity can be properly corrected by orthognathic surgical procedures. In order to prevent the reoccurrence of the deformity and acquire good corrective result, it is essential to remove the affected condyle and to parallel the occlusal canting. PMID- 11769655 TI - [An analysis for causes of skeletal relapse after correction of mandibular prognathism by BSSRO]. AB - OBJECTIVE: To investigate the factors responsible for the skeletal relapse after correction of mandibular prognathism by BSSRO. METHODS: The skeletal and dental changes before and after the surgery were analysed by cephalometrics, The factors that might be responsible for the skeletal relapse were evaluated using multiple linear and partial correlation analysis. RESULTS: The changes of NP-FH angle at follow up had a significant correlation with MP-FHT4-3 angle, the duration of presurgical orthodontics and the observation period after surgery(r = -0.568, 0.406, -0.400, P < 0.01-0.05). CONCLUSION: The skeletal relapse following BSSRO was limited. The stability was related to the period of presurgical orthodontics and the mandibular rotation after the surgery. PMID- 11769656 TI - [The role of TGF-beta on Tca83--a tongue squamous cell carcinoma cell line]. AB - OBJECTIVE: To investigate the role of TGF-beta on the growth of Tca83 cells. METHODS: The cell culture, MTT detection, immunohistochemistry and in situ hybridization detection methods were used. RESULTS: After 96 h, compared with the control, most groups with low concentrations of TGF-beta (0.2, 1.0, 5.0, 12.5 micrograms/L) showed growth inhibition, while the group with high concentration of TGF-beta (25.0 micrograms/L) showed no growth inhibition. Positive stain of TGF-beta 1, T beta R I mRNA and TGF-beta 1, T beta R I, T beta R II protein could be detected in Tca83 cells. CONCLUSIONS: Tca83 cell line has the potentiality to secret TGF-beta 1. Autocrine and paracrine of TGF-beta 1 could regulate cancer cell's proliferation and differentiation directly. Since the ligand-receptor conduction in Tca83 cell line is intact, external TGF-beta 1 could combine with the T beta R I and T beta R II receptor and exert its inhibitory effect on Tca83 cell line. PMID- 11769657 TI - [Effect of fluoride release on flexural strength of fluoride-containing composites]. AB - OBJECTIVE: To study fluoride release and its impact on flexural strength of fluoride-containing composites. METHODS: Experimental composite resins containing 0.3%, 0.6% and 1.2% fluoride (w/w) respectively and non-fluoride control composites were selected, including a compomer and its control composites. The amount of fluoride release in vitro was determined with fluoride ion-sensitive electrode in a 30 day consecutive period. The flexural strength was measured by Autograph Machine before and after releasing fluoride in water. RESULTS: The amount of fluoride release increased (0, 21.98, 43.98 and 99.91 micrograms.cm-2 respectively) and the flexural strength decreased (101.70, 94.29, 82.03 and 79.84 MPa respectively) while fluoride-contents in resins increased (0%, 0.3%, 0.6% and 1.2% respectively). With fluoride release, the flexural strength decreased significantly (P < 0.05). CONCLUSION: Fluoride release affects mechanical properties of fluoride-containing composites. PMID- 11769658 TI - [Epidemiologic survey on mental health of maxillofacial traumatic inpatients]. AB - OBJECTIVE: To Analyze the mental health level of maxillofacial traumatic inpatients. METHODS: The mental test was carried out in 126 maxillofacial traumatic inpatients of Department of Oral and Maxillofacial Surgery of the Fourth Military Medical University from 10/1998 to 09/1999 with the SCL-90 (symptom check list-90). RESULTS: The total mark of SCL-90 was 153.76 +/- 62.44. The number of symptomatic items was 31.52 +/- 24.55, which was higher than that of domestic norm (P < 0.01). The inpatient constitutes at different level of SCL 90 total mark showed normal distribution. The every factor mark of SCL-90 was also higher than that of domestic norm (P < 0.01). The former four factors were melancholy, anxiety, horror and psychosis. The SCL-90 factors mark had an increased trend along with injury severity score (RISS). The age and sex had not notable influence on the mental health level (P > 0.05), but the educational level had notable influence on the mental hralth level (P < 0.05). CONCLUSIONS: The mental health level of maxillofacial traumatic inpatients is lower than normal people and has a decreasing trend along with the RISS. The inpatient that has lower educational level also has lower mental health level. The mental handicap is caused by traumatic event and nosocomial stress. PMID- 11769659 TI - [Experimental study of bacteriostatic activity of Chinese herbal medicines on primary cariogenic bacteria in vitro]. AB - OBJECTIVE: To screen some Chinese herbal medicines for their inhibitory activity on cariogenic bacteria, and investigate their active ingredients, and measure their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC). METHODS: Active components were isolated from every tested Chinese herbal medicine by means of aqueous extraction and ethanolic extraction. Berberine was purified from Coptis chinensis Fra. Disk agar diffusion method was employed in screening herbs with inhibiting effect on cariogenic bacteria. MIC and MBC were determined by broth dilution method. RESULTS: Against Streptococcus mutans Ingbritt, MBCs of Magnolia officinalis ethanolic extract, Berberine, Coptis chinensis Fra aqueous extract and Coptis chinensis Fra ethanolic extract were 0.488, 0.625, 7.800 and 1.950 g/L respectively. Against Streptococcus sobrinus 6715, MBCs of Magnolia extract, Coptis chinensis Fra ethanolic extract, Rhus chinensis Mill ethanolic extract and Phellodendron chinen ethanolic extract were 0.488, 0.625, 1.950, 3.900, 3.900 and 3.900 g/L respectively. Against Actinomyces viscosus ATCC 19246, MBCs of Berberine, Coptis chinensis Fra aqueous extract, Coptis chinensis Fra ethanolic extract, Rheum palmatum L aqueous extract and Rheum palmatum L ethanolic extract were 1.250, 3.900, 3.900, 15.600 and 31.250 g/L respectively. CONCLUSIONS: Magnolia officinalis, Coptis chinensis Fran, Rheum palmatum L aqueous extracts exhibit strong inhibition on cariogenic bacteria. Magnolia officinalis ethanolic extract has the strongest bactericidal effects on Streptococcus mutans and Streptococcus sobrinus. PMID- 11769660 TI - [A study on affecting factors on dental care demands by logistic regression model]. AB - OBJECTIVE: To develop probability model for dental visits based on analysis of the factors affecting people's dental services utilization in urban area of Beijing, thus providing some evidence for forecasting further demanded dental care and building the more efficient oral health care delivery system. METHODS: A cross-sectional survey was conducted amnog 1,517 subjects of all age groups in Beijing selected by stratified, clustering, random sampling. The first model of dental care demand--probability model for dental visits was established with logistic regression. RESULTS: Awareness of oral health showed the most important relationship. Different social background and economic factors also had great effects on demand. Higher demand for care were existed among those who suffered from a disease that was painful or resulted in poor oral function. CONCLUSIONS: It is suggested that dental care has different characters from general health service. Utilization of dental service is largely determined by people's awareness, income and insurance system. So oral health education should be extended in order to promote the effective demands and reduce the potential demands. Rational oral health insurance system should be set up to provide some priority to certain people, thus stimulating the supply of dental care and improving the utilization of dental service. Since raising price for care will restrain the low-incomer's basic demand, and it will neither add the profit nor improve people's oral health, the price decision should be considered carefully. At last, oral health care should be emphasized on children and adolescent as priority age groups based on the conclusion from demand model. PMID- 11769661 TI - [Relationship between maternal nutritional stetus and intrauterine growth retardation with neonatal visual development disorder]. AB - OBJECTIVE: To investigate the relationship between the maternal nutritional stetus and the occurrence of intrauterine growth retardation (IUGR) with neonatal visual development disorder. METHODS: Sixty pregnant women closed to expected date of confinement were randomly divided into 2 groups: IUGR and normal control group, each were with 30 cases. Eight kinds of nutritional foods taken by the pregnant women were investigated and scored. The vitamin A concentrations of maternal and umbilical blood were measured with fluorometer method. The concentrations of iron, copper and zinc in maternal and umbilical blood were detected by spectrophotometer. The results of examination with Flash-visual evoked potentials (F-VEP) were recorded by an experienced technician in neonates at 3-7 days after birth and 10 months after follow-up. RESULTS: Compared with the normal control, the IUGR group had taken less eggs, animal liver and fat pork during pregnancy (P < 0.05), had remarkable lower concentrations of vitamin A and iron in maternal and umbilical blood (P < 0.01), and had a lower umbilical blood zinc concentration (P < 0.05). Meanwhile, neonates with IUGR had obvious delay of the latent period of F-VEP's main positive component (P100) (P < 0.05) and an attenuation of the P100 with when it was measured at 3-7 days after birth and at 10th month after fellow-up (P < 0.01). CONCLUSION: The decreased intake of foods rich in vitamin A, iron, zinc and other nutritional components was closely correlated with IUGR occurrence and resulted in retardation of neonate visal development. PMID- 11769662 TI - [Clinical application of ultrasonographic indexes for assessment of amniotic fluid volume]. AB - OBJECTIVE: To find the favorable interval of assessment of amniotic fluid volume and the optimal standard for oligohydramnios. METHODS: To determine actual amniotic fluid volume (AAFV) by collecting amniotic fluid during cesarean section and compare it with maximum vertical pocket (MVP) and amniotic fluid index (AFI) in different interval between cesarean section and measurement and test the sensitivity and specificity of MVP and AFI of different standard. RESULTS: The ultrasonographic results were divided into three groups according to the interval between measurement and delivery: within 24 hours group, 24-96 hours group and longer than 96 over hours group. The results of the within 24 hours and 24-96 hours groups were positively correlated with AAFV, while the results of the group longer than 96 hours were not statistically significant. The correlation coefficients were 0.840 and 0.869 for MVP, 0.789 and 0.874 for AFI respectively. The receiver-operator characteristic curve showed that MVP < 4 cm and AFI < 10 cm were superior to any other standards to scan oligohydramnios. The sensitivity of these standards was 0.76 and 0.61, and the specificity was 0.83 and 0.91. CONCLUSION: It is highly recommended to estimate the amniotic fluid of high risk pregnant women, women with MVP < 4 cm or AFI < 10 cm and with a pregnancy week > 40 weeks should be monitered by ultrasonography every four days. PMID- 11769663 TI - [Effect on the pregnant woman and fetus by multiple hepatitis virus infection]. AB - OBJECTIVE: To evaluate the effect on the pregnant woman and fetus by infection of multiple hepatitis virus during pregnancy. METHODS: Hepatitis virus A, hepatitis virus B, hepatitis virus C, hepatitis virus D and hepatitis virus E were determined in the pregnant women with abnormal liver function during 1994-1999. Patients diagnosed to be infected by single hepatitis virus or multiple hepatitis virus were divided into two groups and complications of the pregnant woman and fetus and their prognosis were evaluated. RESULTS: There were no significant differences in the levels of alamine transaminase (ALT), aspartama transaminase (AST) and total bilirubin (TBIL) between the multiple hepatitis virus infection group (multiple group) and the single hepatitis virus infection group (single group) (P > 0.05). The positive rate of HbeAg (35.7%) in multiple group was significantly lower than in single group (P < 0.05). However, the positive rate of HbeAb (57.1%) in multiple group was significantly higher than in single group (P < 0.01). There were no significant differences in incidences of pregnancy induced hypertension (PIH), postpartum hemorrhage, serious symptoms and mortality between the multiple hepatitis virus infection group and the single hepatitis virus infection group (P > 0.05). However, the incidences of premature rupture of membrane (PROM), premature delivery, 28.1%, 25.0% fetal distress and newborn infant asphyxia 31.3%, 25.0% in multiple hepatitis virus infection group were significantly higher than in single hepatitis virus infection group (P < 0.05, P < 0.01). CONCLUSIONS: Multiple hepatitis virus infection during pregnancy has no more serious effect on the pregnant woman, but has worse effect on fetus than single hepatitis virus infection. The obstetrician should pay more attention to the health care of the pregnant woman with the multiple hepatitis virus infection to prevent PROM and premature delivery, at the same time monitor fetus carefully and deal with labor actively to decrease the mortality of the fetus. PMID- 11769664 TI - [Longitudinal study about the function of pituitary-thyroid axis in pregnancy]. AB - OBJECTIVE: To evaluate the change about the function of pituitary-thyroid axis and the role of human chorionic gonadotropin (hCG) on regulation of pituitary thyroid axis in pregnancy. METHODS: The study was designed to provide longitudinal information of parameters of thyroid function and hCG in 74 healthy women during pregnancy and after delivery. Serum free triiodothyronine (FT3), free thyroxin (FT4), TT3, TT4, hCG and thyroid hormone binding globulin (TBG) concentrations were measured with radioimmunoassary and serum TSH concentration with immunoradiometric assay. RESULTS: (1) The FT3 and FT4 values below the reference range were 5.88% and 9.80%, respectively, in third trimester and after delivery, both were 38.10%. The serum TSH level below the reference range was 31.25% in first trimester and supranormal were 11.90% after delivery. The serum hCG level at all stages of pregnancy was higher than postpartum. (2) The serum FT3 level was significantly higher in first (4.37 +/- 0.78) pmol/L and second (4.75 +/- 0.90) pmol/L trimesters than postpartum (2.96 +/- 0.84) pmol/L, decreased in third trimester (3.94 +/- 0.75) pmol/L and the lowest level after delivery. The serum FT4 level was significantly higher in first (14.07 +/- 1.44) poml/L and second (12.86 +/- 0.84) pmol/L trimesters than postpartum (10.45 +/- 1.45) poml/L, decreased in third trimester (11.29 +/- 1.00) pmol/L and the lowest level after delivery. (3) The serum TSH level was the lowest values in early pregnancy (0.88 +/- 0.83) mU/L, showed significant increase in second (1.86 +/- 1.04) mU/L and third (1.48 +/- 0.90) mU/L trimesters and reached maximal level after delivery (2.82 +/- 1.42) mU/L. (4) The serum hCG level was the highest in early pregnancy (309.05 +/- 320.02) micrograms/L, then significant decreased in second (69.11 +/- 19.18) micrograms/L and third (86.25 +/- 44.60) micrograms/L trimesters and was the lowest levels after delivery (29.92 +/- 20.91) micrograms/L. (5) A significant negative correlation between TSH and hCG levels and a significant positive correlation between hCG and FT4 and TT4/TBG were demonstrated. CONCLUSIONS: (1) hCG may be as role on regulation of pituitary thyroid axis during pregnancy and during certain time of postpartum. (2) After delivery, part of women were transient hypothyroxinemia. PMID- 11769665 TI - [Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women]. AB - OBJECTIVE: To evaluate the effect and feasibility of using estrogen cream for the prevention and treatment of recurrent urinary tract infection (UTI) in postmenopausal women. METHODS: Forty-five postmenopausal women with a history of recurrent UTI were divided into two groups (group premarin and group antibiotic). Participants were assigned to apply intravaginal premarin cream (group premarin, n = 30) or oral antibiotic (group antibiotic, n = 15) for 3 months respectively. Urine routine test, midstream urine and vaginal cultures, vaginal health score (VHS), vaginal cell maturation value (MV), endometrial thickness and blood estrogen level were obtained before and after the study. RESULTS: The incidence of UTI in the group premarin was significantly reduced as compared with that in the group antibiotic (2/27 vs. 12/15, P < 0.001). In the group premarin Lactobacilli reappeared (from 0 to 59.3%) and MV (from 9.2 +/- 6.8 to 74.6 +/- 14.1) and VHS (from 5.2 +/- 0.4 to 13.4 +/- 2.5) were improved after 3 months. There was no significant change in the group antibiotic. CONCLUSION: It seems that intravaginal use of estrogen cream would effectively prevent and reduce the UTI in postmenopausal women. PMID- 11769666 TI - [Analysis of pregnancy rates after treatment of tubal pregnancy with systemic methotrexate]. AB - OBJECTIVE: To analyse the pregnancy rate after treatment of tubal pregnancy with the systemic methotrexate (MTX) injection. METHODS: From March 1985 to August 1999, 129 women with confirmed unruptured tubal pregnancy, and desiring to conceive were selected. Among them 60 women were successfully treated with systemic MTX, and 69 with unilateral salpingectomy. All cases were followed up for 1-15 years. RESULTS: The rates of subsequent intrauterine pregnancies (IUP) in the MTX group was 73% (44 cases) and of recurrent extrauterine pregnancies (EP) was 8% (5 cases). Among 69 patients treated by salpingectomy, the rates of IUP and EP was 70% (48 cases) and 4% (3 cases) respectively. The differences between the two groups were not statistically significant. CONCLUSIONS: The effect of conservative management with MTX was similar to those of salpingectomy. The rate of subsequent pregnancy did not increased. PMID- 11769667 TI - [Preliminary study on application of blastocyst culture and day 5 transfer in patients with low oocyte number]. AB - OBJECTIVE: To evaluate whether blastocyst culture and transfer in patients with low oocyte number can effectively improve the outcome of in vitro fertilization embryo transfer treatment. METHODS: Retrospectively analyze 59 couples received conventional in vitro fertilization and embryo transfer (IVF-ET) treatment in our center from January to February 2000. Twenty-one couples had blastocyst culture and day 5 embryo transfer and another 38 couples had day 2 embryo transfer as the control. Their clinical and laboratory results were compared between these two groups. RESULTS: In day 5 group the mean oocytes retrieved were (6.6 +/- 2.8), the clinical pregnancy rates (PRs) was 43% and the life delivery rate was 38%; while in day 2 group the results were (6.9 +/- 3.7), 37% and 29% respectively. There was no significant difference between two groups. No high-order multiple birth occurred in day 5 group, but in day 2 group there were two cases: one with triplets and another with pentadriplet who had the embryos reduction. CONCLUSIONS: These results demonstrate that nonselective blastocyst culture and transfer in patients with low oocyte number seems not effectively to improve the PRs and the delivery rate, but may decrease the occurrence of multiple birth without affecting the final pregnancy results when compared with conventional day 2 transfer. PMID- 11769668 TI - [Pathogens of transmitted disease in the pathogenesis of acute pelvic inflammatory disease]. AB - OBJECTIVE: To study the pathogenesis of pathogens of sexually transmitted disease (STD) in acute pelvic inflammatory disease (PID). METHODS: Neisseria gonorrhoeae, chlamydia trchomatis, ureaplasma urealyticum were cutured respectively in 130 patients with acute PID. RESULTS: The pathogens of STD had been found in 55 patients. The detective rate of Neisseria gonorrhoeae was 6.9% (9/130), about half of them were mixed infection; the detective rate of chlamydia trachomatis was 4.6% (6/130), all of them were mixed infection; the positive percentage of ureaplasma urealyticum was 37.7% (49/130), one third of them were mixed infection. CONCLUSION: The pathogens of STD might cause acute PID or only play a synergetic role in it. PMID- 11769669 TI - [Relationship between the expression of connexin 43 and bystander effect of suicide gene therapy in ovarian cancer]. AB - OBJECTIVE: To explore the relationship of connexin 43(Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) gene therapy in vitro, and to investigate the effection of all-trans retinoic acid (RA) on expression of Cx43 and bystander effect. METHODS: Cx43 expression was examined with flowcyto-metry, Western Blot, and immunofluorescence in two ovarian tumor cells OVCAR3, CAOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. RESULTS: Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than in CAOV3 (P < 0.05). The expression of Cx43 was detected in OVCAR3 with flowcytometry and Wstern Blot, but it could not be detected in CAOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluorescence staining showed that OVCAR3 Cx43 protein is located in membrane surface, whereas CAOV3 is in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. CONCLUSIONS: There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be inhanced by RA in ovarian cancer. PMID- 11769670 TI - [A novel antiapoptosis gene, survivin, bcl-2, p53 expression in cervical carcinomas]. AB - OBJECTIVE: To study the expression of a novel inhibitor gene of apoptosis, survivin, in cervical carcinoma and its relationship with the expression of bcl 2, p53 genes. METHODS: Using streptavidin-biotin peroxidase (SP) method, we examined the expression of survivin, bcl-2 and p53 genes in 10 normal cervical tissues and 59 cervical carcinoma tissues. RESULTS: Survivin was expressed in 41 of 59 (69.5%) cases of cervical carcinomas. In contrast, normal cervical epithelium did not express survivin. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with bcl-2 expression (36/45, 80.0% versus 5 of 14 cases, P < 0.005) and p53 expression (33/43, 76.7% versus 8 of 16 cases, P < 0.05). CONCLUSIONS: Apoptosis inhibition by survivin, alone or in cooperation with bcl-2 and p53 may participate in the onset and progression of cervical carcinoma. Survivin could be a new diagnostic/therapeutic target in cervical cancer. PMID- 11769671 TI - [Establishment of the drug resistant cell line of choriocarcinoma and the reversal of drug resistance by transfection of human interleukin 2 gene]. AB - OBJECTIVE: To establish the drug-resistant cell line of choriocarcinoma and to study the transfection of the human interleukin 2 (hIL-2) gene into the established drug resistant cell line and investigate the reversal of the multidrug resistance. METHODS: The resistant cell line was established by pulse exposed choriocarcinoma cell line JEG-3 to etopside (VP-16) for ten months. The recombinant plasmid containing pcDNA3.1(+)-hIL-2 gene was constructed. The drug resistant cell line was transfected with the constructed plasmid by lipofectin, and the tumor cell colonies containing the IL-2 sequence were selected by genetin. The expression of hIL-2 and drug resistant-related genes was detected by reverse transcript polymerase chain reaction. The chemosensitivity of the gene transfected tumor cells and the non transfected cell lines to methetraxate, VP 16, kengshengmycine, paclitaxol and 5-fluorouracil was determined by the methyl thiazolyl tetrazolium cytotoxicity assay. RESULTS: The transfected cells expressed human hIL-2 gene, and showed the reversal of multidrug resistance by methyl thiazolyl tetrazolium assay. The transfected cells expressed no multidrug resistance gene-1 (MDR1) on mRNA level. Drug resistance index to VP-16 decreased from 38.7 to 6.0 and 6.1, the index to methetraxate decreased from 14.5 to 2.6 and 2.5, to methetraxate from 13.0 to 2.0. CONCLUSION: The transfection of hIL-2 gene into the drug resistance cell line of choriocarcinoma can modulate the MDR1 expression on the mRNA level, and reverse the drug resistance. PMID- 11769672 TI - [Lay stress on distinguishing the primary bone marrow hematopoietic failure]. PMID- 11769673 TI - [The significance of nucleotide repeat sequences in FVIII gene for detecting hemophilia A carriers]. AB - OBJECTIVE: To detect the carriers in hemophilia A(HA) families by haplotype analysis of the microsatellite polymorphisms at intron 13 [13(CA)n] and 22[22(GT)n(AG)n] in the factor VIII (FVIII) gene. METHOD: Multi-PCR amplification of 13(CA)n and 22(GT)n(AG)n combined with silver staining were used. RESULTS: In 35 HA families, 11 had HA history. There were 21 female members in the 11 HA families and all of them were subjected to molecular study. Fourteen of the 21 females were confirmed to be carriers and approximately 72.7%(8 of 11) of these families were informative. CONCLUSIONS: Besides the reliable detection of HA carriers, multi-PCR combined with silver staining in HA analysis has the advantages of time saving, simplicity for performing and no radiation contamination. PMID- 11769675 TI - [Detection of -5/5q- chromosome abnormality in myelodysplastic syndromes by interphase fluorescence in situ hybridization]. AB - OBJECTIVE: To evaluate the value of interphase fluorescence in situ hybridization(FISH) in the detection of acquired complete and partial deletion of chromosome 5(-5/5q-) in myelodysplastic syndromes (MDS). METHODS: Marrow cells from 48 MDS patients and 10 normal controls were studied by interphase FISH using SpectrumRed directly labelled DNA specific probe for 5q31, 200 to 300 cells were scored for each case and cells with a red hybridization signal > 6% were defined as -5/5q- positive. RESULTS: In 48 MDS patients, 13 were positive for interphase FISH, of whom, 7 were positive and 6 were negative for conventional cytogenetics (CC). The difference in the percentage of positive cells detected by the two methods was statistically significant (P < 0.05). CONCLUSION: Interphase FISH is more sensitive than CC for the detection of -5/5q- in MDS. PMID- 11769674 TI - [The prevalence of beta-thalassemia heterozygotes compound alpha-thalassemia in Guangdong district]. AB - OBJECTIVE: To investigate the prevalence of beta-thalassemia (beta-thal) heterozygotes compound alpha-thal in Guangdong area. METHODS: alpha-thal 1 genes were amplified in 500 beta-thal carriers diagnosed by reverse dot blotting (RDB) using gap-PCR method, alpha-thal 2 genes were detected in 400 of the 500 beta thal carriers using Southern blotting with alpha-globin DNA probe and restrict endonuclease zymogram analytical method. RESULTS: Forty three alpha-thal-1(alpha alpha/- -SEA) cases were identified in the 500 beta-thal traits, and 26 alpha thal 2 including 17 rightward deletion (alpha alpha/- alpha 3.7) and 9 leftward deletion(alpha alpha/-alpha 4.2) cases were identified in the 400 beta-thal traits. CONCLUSION: The prevalence of beta-thal heterozygote carrying alpha-thal 1 gene was 8.6% and that of beta-thal heterozygote carrying alpha-thal-2 gene was 6.5% (4.2% rightward deletion and 2.2% leftward deletion). PMID- 11769676 TI - [Preliminary study on postremission therapy courses in acute myeloid leukemia]. AB - OBJECTIVE: To explore the optimum postremission therapy courses in acute myeloid leukemia (AML). METHODS: Data from medical records of AML patients in our hospital in 7 year were analyzed with SPSS 8.0 system software. RESULTS: One hundred and ninety one untreated de novo AML patients received different induction chemotherapy regimens: HA, DA, AA and HAD. The complete remission (CR) rate was 81.4%, 89.9% for one to two courses. The median disease free survival (DFS) in 144 CR patients whose survival time could be analyzed was 9.6 months. The probability of survival was 21.6% at 3 year and 12.9% at 5 year. For the patients received less than 6 courses of post-remission therapy, the median DFS was 7.1 months and the probability of survival was 11.4% at 3 year and 6.3% at 5 years, Whereas for patients received 6 or more courses of post-remission therapy, they were 35.3 months, 43.2% and 27.0%, respectively. The differences between the two groups were statistically significant. For patients received 8 or more courses of post-remission therapy, the median DFS was 48.8 months and the probability of survival was 57.9% at 3 year and 31.6% at 5 year. CONCLUSION: AML patients should at least receive 6 courses of post-remission therapy, and 8 courses therapy seems better. PMID- 11769677 TI - [The role of exogenous hRAR beta gene on the growth inhibition and differentiation induction of HL-60R Cells]. AB - OBJECTIVE: To investigate the role of hRAR beta gene in HL-60R cells and in their response to retinoids. METHODS: By electroporation, the recombinant pcDNA3-hRAR beta plasmid was transfected into the hRNA beta gene not expressed human myleocytic leukemic cell line HL-60R. In the presence of RAR-selected agonist Ch55, the effect of RAR beta gene on HL-60R was studied by the efficiency of colony formation in soft agar, cell morphology NBT reduction assay and flow cytometry. RESULTS: The HL60R-hRAR beta cells with stable hRAR beta gene expression were obtained. The growth and colony formation in soft agar of HL60R hRAR beta cells were remarkably reduced as compared with that of their parent cells, and the cells were induced into granulocytic differentiation by Ch55 treatment at 10(-7). CONCLUSION: The expression of exogenous hRAR beta gene in HL 60R cells could resume their sensitivity to retionoids in inhibiting cell proliferation and inducing granulocytic differentiation. PMID- 11769678 TI - [The implications of the biological indices examination of bone marrow cells in myelodysplastic syndromes]. AB - OBJECTIVE: To explore the biological characteristics of the hematopoietic cells in myelodysplastic syndromes(MDS) and the relationship between the biological indices and the disease progressing. METHODS: R banding technique for karyotype analysis, in vitro semi-solid culture for CFU-GM growth patterns, flow cytometry after monoclonal antibody labeling for proliferation cell nuclear antigen (PCNA) expression, flow cytometry after in vitro bromodeoxyuridine (BrdU) incorporation for cell cycle kinetics analysis, and X-linked HUMARA gene polymorphism assay for hematopoiesis clonality analysis were carried out in 37 MDS patients. RESULTS: 1. Cytogenetic abnormalities were detected in 31% of the MDS patients and AML transformation occurred in 2 of 9 with normal and 3 of 5 with abnormal chromosomal karyotypes. 2. The mean CFU-GM colony yield was decreased and cluster yield increased in the MDS patients. Disease progression in 6 of 9 with more CFU GM cluster yields, while only 1 of 9 with either normal or no CFU-GM yields transformed into AML. 3. Percentages of PCNA-positive BMMNCs were significantly higher in MDS patients than in normal control (44.22% vs 26.82%, P < 0.01). RAEB/RAEB-t subtypes had significantly higher PCNA-positive cells (P < 0.01). 4. The mean BrdU labeling index of MDS marrow cells was lower (5.07%), the mean DNA synthesis time (Ts) and potential doubling time(Tpot) of MDS patients were longer than that of normal control (p < 0.01), and the increased Ts and T pot were related to the disease progression. 5. Monoclonal pattern of BMMNCs was detected in 5 of 7 heterozygous female RA patients and the other 2 were polyclonal hematopoiesis. All 3 RAEB and 1 MDS/AML were monoclonal hematopoiesis. CONCLUSION: With disease progressing and bone marrow blasts increasing, the biological nature of the hamatopoetic cells in MDS exhibited a tendency to transformation as follows: hematopoiesis converting into clonal, in vitro CFU-GM growth pattern approaching leukemic, PCNA expression increasing, and cell cycle prolonging. PMID- 11769679 TI - [A preliminary study on translocation of the immunoglobulin heavy chain gene in KM3 myeloma cell line]. AB - OBJECTIVE: To identify the IgH translocation in KM3 myeloma cell line established from a Chinese patients. METHODS: Southern blotting was performed with dig labeled probes specific for IgH switch regions to identify and distinguish IgH switch recombination events. RESULTS: Besides a 10.0 kb Hind III fragment being able to hybridize with both 5' S mu and 3' S mu probes as that in placenta genome DNA. There was a 5.6 kb Hind III fragment in KM3 genome DNA could only hybridize with the 3' S mu probe. CONCLUSION: There was an illegitimate switch recombination fragment containing 3' S mu region in the KM3 myeloma cell line, which was caused by the IgH translocation involving the IgH S mu region. PMID- 11769680 TI - [Treatment of acute aplastic anemia with allogeneic peripheral blood stem cell transplantation: a case report and literature review]. AB - OBJECTIVE: To report a patients with acute aplastic anemia(AAA) successfully treated with allogeneic peripheral blood stem cell transplantation(allo-PBSCT). METHODS: A 30 years old patient with AA received allo-PBSCT from a HLA-compatible sibling donor. PBSCs mobilization regimen was G-GSF 250 micrograms/d x 6. The conditioning regimen included (CTX 50 mg.kg-1.d-1) x 4 and (ATG 10 kg-1.d-01) x 2. 8.97 x 10(8) nucleated cells/kg, 9.20 x 10(6) CD34+ cells/kg, 11.20 x 10(5) CFU-GM/kg were transplanted. RESULTS: Hematopoietic reconstitution obtained on day 18 after allo-PBSCT. Monitoring of engraftment with three microsatellite markers showed mixed chimerism on day 18 and complete chimerism after day 25. No acute or chronic graft versus host disease (GVHD) occurred. In the follow-up duration of 240 days, the blood and bone marrow pictures were normal and the living status was good. CONCLUSION: Allo-PBSCT was an effective therapy in the treatment of acute aplastic anemia. PMID- 11769681 TI - [Cloning and biological regulating effects of human WAF1 gene]. AB - OBJECTIVE: To clone human WAF1 gene and construct WAF1-pcDNA3 recombinant plasmid, and to explore the biological regulating effects of WAF1 gene. METHODS: Human WAF1 gene was amplified and cloned into pcDNA3 vector by RT-PCR and DNA direct sequencing from Hela cells. By immunofluorescence and immunohistochemistry staining, the identify the expression of the inserted WAF1 gene and its biological regulating effects on Rb, cyclin D1 gene. RESULTS: Human WAF1-pcDNA3 recombinant plasmid was correctly constructed and transfected into Hct-8 cells. P21WAFI/Clip was successfully expressed. The functional characterization of the inserting WAF1 gene implied that P21WAF1/Cip1 expression could upregulate Rb gene and downregulate cyclin D1 gene at protein level. CONCLUSION: Human WAF1-pcDNA3 can modulate the protein expression of the downstream gene. PMID- 11769682 TI - [Dynamic surveillance of risk behaviors facilitating sexually transmitted disease/acquired immunodeficiency syndrome transmission among permanent residents in Kunming city in 1996-1999]. AB - OBJECTIVE: To monitor the trends of risk behaviors promoting sexually transmitted disease/Acquired immunodeficiency syndrome (STD/AIDS) transmission among general public in order to develop appropriate intervention strategies and to evaluate impact of intervention programs. METHODS: Two hundred subjects were randomly selected and interviewed every other month in Kunming city from 1996 to 1999. STD AIDS-related information on knowledge, attitudes and behavior were collected during the interview. RESULTS: The knowledge of STD and AIDS transmission increased from 49.2% to 62.8% (chi 2 = 96.5, P < 0.01) and from 16.6% to 35.2% (chi 2 = 146.5, P < 0.01), respectively. Knowledge on condom use and attitude to AIDS did not change much. Self-reported prevalence of risk behaviors remained low. Residents aged between 15 and 39 had unprotected sex behavior (0.8%-2.5%) and drug use (0.3%-2.4%). CONCLUSION: The awareness on STD and AIDS transmission increased gradually. Risk behavior of STD/HIV infection existed among residents aged between 15 and 39 years, which called for intervention programs in the future. PMID- 11769683 TI - [A community-based acquired immunodeficiency syndrome education intervention study in Kunshan county]. AB - OBJECTIVE: To evaluate the effectiveness of a community-based acquired immunologic deficiency syndrome (AIDS) educational intervention in young adults. METHODS: A quasi-experimental design was used. Two townships in Kunshan county, matched by socioeconomic characteristics, were randomly assigned to intervention or control groups. Eight hundred young adults aged 18-30 were recruited from the two townships as study subjects. A 12-month comprehensive educational intervention on AIDS prevention was conducted in the intervention group through local family planning services. RESULTS: After intervention, subjects in intervention group significantly improved their knowledge on AIDS and attitudes related to AIDS prevention. Reported rate of condom use during the last episode of sexual intercourse increased from 8.5% at baseline to 14.4% after intervention (chi 2 = 4.66, P = 0.030 8). No obvious change was observed among subjects in control group. CONCLUSION: This study demonstrated the feasibility of integration of AIDS educational intervention into the existing family planning services. Integration of AIDS programs into family planning program should be considered as a realistic approach for AIDS control in China. PMID- 11769684 TI - [Acceptability and feasibility of promoting condom use among families with human immunodeficiency virus infection in rural area of China]. AB - OBJECTIVE: To study the acceptability and feasibility of promoting condom use among families with human immunodeficiency virus (HIV) infection in rural area of China. METHODS: Ninety families with HIV infection were selected. Education, skill training on condom use and distribution of condoms were carried out. Two cross-sectional surveys were carried out before and after intervention to compare the difference of condom use rate. RESULTS: Eighty-four families finished the study, with a follow-up rate of 93.3%. The rate of use condom for every sexual intercourse in the last month increased from 2.6% before intervention to 71.4% after intervention (P < 0.001). After controlling other confounders, intervention is a strong independent predictor for increased condom use in infected couples. CONCLUSION: Promoting condom use among families with HIV infection in the rural area is acceptable. To reduce risk of sexual transmission of HIV within couples, families of the HIV infected persons need to be informed in no time. PMID- 11769685 TI - [Evaluation on peer education program among injecting drug users]. AB - OBJECTIVE: To reduce risk behaviors which promotes human immuno deficiency virus (HIV) transmission among drug users. METHODS: A peer education program was implemented among drug users in drug detoxification centers in Kunming from May 1998 to June 2000. Before and after intervention, through random sampling, subjects were recruited to assess the impact of the program. Focus group discussion and a small sample of follow-up in communities were used for evaluation. RESULTS: Three hundred and six and 418 subjects were interviewed before and after the intervention program. Rates regarding "sharing needles" had a reduction from 68.3% to 62.0% (chi 2 = 2.61, P < 0.01, while "never cleaning a needle" increased from 3.3% to 15.8% (chi 2 = 19.41, P < 0.01), and "used needles disposal to garbage bin" increased from 58.4% to 81.8% (chi 2 = 40.23, P < 0.01). Thirty-four drug users were followed in their communities and 67.6% were no longer sharing needles but none reported using a condom when having casual sex. CONCLUSION: Peer education program among drug users in detoxification centers had limited impact. In order to control the epidemic of AIDS in drug using population, more effective strategies need to be explored. PMID- 11769686 TI - [Survey on the high risk behaviors related to acquired immunologic deficiency syndrome and sexually transmitted diseases among men who have sex with men in mainland China]. AB - OBJECTIVE: To understand the high risk behaviors related to acquired immunologic deficiency syndrome (AIDS) and sexually transmitted diseases (STDs) among men who have sex with men (MSM) in mainland China. METHODS: A self-administrated anonymous mail survey was carried out in MSM throughout the mainland of China in 1999. RESULTS: One thousand eight hundred questionnaires were mailed out and 729 effective questionnaires were collected. The response rate was 40.5%. The average age of subjects was 31 years old. Their average age at first sexual intercourse with a man was 18.6 years old. Average number of male sexual partners were 39.2 out of which 75.7% reported having had anus-intercourse. In the latest year, 63.6% reported ever having sex with strange men, 39.8% reported ever having group sex, 9.3% reported having sold sex and 3.8% having bought sex. 50% of them reported ever having sex with women. One hundred thirty-three reported having been diagnosed STD. Sixty-two reported having tested for HIV antibody and 11 were positive. Two-thirds reported ever using a condom when having sex. CONCLUSION: High risk sexual behaviors were prevalent among MSM in mainland China with HIV infection rate already reaching a high level. Women having sex with MSM are at a greater risk of HIV infection. PMID- 11769687 TI - [Study on sexual and drug use behaviors of high risk among sex workers in entertainment in establishments in Shanghai]. AB - OBJECTIVE: To understand the types of entertainment establishments involved in commercial sex and Acquired immunodeficiency syndrome (AIDS) related risk behaviors among sex workers. METHODS: One district in Shanghai was selected. All entertainment establishments in the district were mapped. In-depth interview was carried out to collect information about demographic, sexual, drug use, measures of self-protection, condom use, history with sexually transmitted disease (STD) and health care seeking behaviors. RESULTS: Sixty-three sex workers were recruited from 38 places, of which, 38 from beauty parlors, 13 from pubs/bars and sauna settings, 10 from KTV and 2 freelance. The average age was 25 (17-45) years old. 73% were not permanent residents. Thirty-seven had reportedly engaged in commercial sex activities. Some reportedly had sex even during menstruation and involved in-group sex. Five drug users and 3 of them reported injecting and sharing needles. Ten of them knew that other sex workers had used drugs. Sixteen (25%) reportedly using condoms but only 4 for disease prevention. Another 2 reported consistent condom use with clients but never used with boyfriends or steady partners. Twenty-two (35%) reported suffering from STDs at least once. Twenty-six (41%) reported seeking care when having diseases, with 38% going to public clinics, 27% to pharmacy and 35% to private clinics. CONCLUSION: AIDS related sexual and drug injecting high-risk behaviors were common among sex workers in Shanghai. Specific and effective interventions, particularly the implementation of 100% condom use program at all entertainment establishments are called with much urgency. PMID- 11769688 TI - [Geographic distribution and feature of Yersinia pestis plasmid isolated from Yunnan province]. AB - OBJECTIVE: To analysis the molecular-epidemiological feature of Yersinia pestis plasmid isolated from Yunnan. METHODS: One thousand and twenty strains of Y. pestis isolates from 44 counties of Yunnan province in China and the border of China-Myanmar using Kado and Liu method and detected by agrose gel electrophoresis. RESULTS: Results showed that these strains from Yunnan province carried 9 kinds of plasmids with molecular weights about 3.93, 6.05, 22.97, 35.65, 45.35, 64.82, 74.59, 111.36 and 129.55 x 10(6). Of these, three kinds of 3.93, 35.65 and 111.36 x 10(6) were found very specific, only reported in Yunnan. The plasmid profile could be divided into 10 types according to the plasmid content. Type I-V were common and had a clustering nature in geographic distribution. CONCLUSION: Based on the plasmid profile, the epidemic districts of plague could be divided into several independent plague foci, suggesting that the resurgence of domestic rat caused plague epidemics might have several hidden plague foci as the result of epidemics since 1982 in Yunnan. PMID- 11769689 TI - [Characterization and distribution of hepatitis B virus genotypes and subtypes in 4 provinces of China]. AB - OBJECTIVE: To determine the distribution and genetic relationship of hepatitis B virus (HBV) genotypes and subtypes. METHODS: HBV genotypes and subtypes were determined by PCR and DNA sequencing among 280 chronic HBV carriers in 25 counties of 4 provinces (Hunan, Guangxi, Henan and Hebei) in China. RESULTS: Genotype B, C and D were detected in these regions. Genotypes C and B were the majority genotypes of HBV with 190 cut of 280 (67.9%) genotype C, 82 (29.3%) genotype B, and 8 (2.9%) genotype D. Adr, adw2, ayr, ayw1, ayw2 and ayw3 subtypes were determined among these carriers. Adr and adw2 subtypes were the leading subtypes of HBV, taking up 64.3% and 31.4%, respectively. Adr subtype was completely encoded by genotype C while majority of adw2 subtype was encoded by genotype B. An average rate nucleotide substitutions of 2.94 was seen among 280 Chinese HBV sequences. The average rate of nucleotide substitutions of genotype B (adw2 subtype) was 5.63 (5.48), but only 1.6 (1.51) for genotype C (adr subtype). CONCLUSION: The results suggested that there were significant differences in geographic distribution of HBV genotypes and subtypes; genotype B, in which mostly consistent with adw2 subtype, was a higher variable than genotype C (adr subtype). PMID- 11769690 TI - [Experimental study on the roles of gasmid mite and chigger mite in the transmission of hemorrhagic fever with renal syndrome virus]. AB - OBJECTIVE: To study the roles of gasmid mite and chigger mite in the transmission of hemorrhagic fever with renal syndrome virus (HFRSV). METHODS: Natural gasmid mite, the first generation gasmid mite, chigger mite larvas from rats, free chigger mite larva and nymph were collected and their cells were cultured to study the role of transmission HFRSV. RESULTS: HFRSV was detected from mite cells after cultured for 15 and 20 days. The number of HFRSV and fluorescence intensity detected from the fhird and fourth generation gasmid mite and chigger mite nymph was much more than those from the first, second generation and chigger mite larva. CONCLUSION: Gasmid mite and chigger mite had an important role to play on HFRSV transmission in keeping the natural cycles. PMID- 11769691 TI - [Analysis on the genotype of measles virus epidemic strains in Dongguan city, Guangdong province in 2000]. AB - OBJECTIVE: To analyze the genotype of the measles virus epidemic strains in Dongguan according to the patients suffered measles in 2000. METHODS: The saliva of 55 patients with acute measles symptoms were collected and detected with RT PCR. The PCR products of the 5 samples were sequenced and analyzed with the software DNASTAR. RESULTS: The positive detection rate was 87.3%, whereas the positive rate of anti MV-IgM in serum was only 70.9%. 68.8% of the saliva samples of patients with anti MV-IgM negative results showing MV RNA positive. The 293 bp fragment of N gene and 194 bp fragment of M gene were amplified from the vaccine virus and the specimens. The sequences of the epidemic strains were identical in both M gene and N gene. CONCLUSION: These results suggested that the outbreak came from a single MV strain. The epidemic strain was obviously different from the standard strains discovered in other countries of the world (the deviation were 1.4%-11.7%) that might belong to H genotype. PMID- 11769692 TI - [An epidemic investigation of eperythrozoonsis in Shandong province]. AB - OBJECTIVE: To learn the status of infection of eperythrozoonsis in Shandong province. METHODS: Seven hundred and seventy-six human blood samples, 198 domestic animal blood samples and 114 wild rat blood samples were collected. Eperythrozoon was detected in the human and animal blood stain slides under microscope. RESULTS: Overall infection rate of Eperythrozoon in human population was 7.3%. Rates were significantly different (P < 0.01) in different districts but no significant difference was found between men and women (P > 0.05). The rate among adults was higher than that of teenagers and elderly. It was also noticed that the rates of people affected with chronic diseases as hepatitis, diabetes and arthritis were higher than those without. The infection rates of goat, cows and rats were 15.6%, 3.2% and 0, respectively. CONCLUSION: Data showed that Eperythrozoon infection was intensively identified in the people and animals in Shandong province. PMID- 11769693 TI - [A case-control study on the risk factors of stomach cancer in Tianjin city]. AB - OBJECTIVE: To explore the risk factors of stomach cancer in Tianjin. METHODS: A matched case-controls study was carried out. A total number of 189 patients with stomach cancer who were individually matched and interviewed. RESULTS: Multivariate conditional logistic analysis showed that stomach cancer was closely relate to the four factors: smoked food (OR = 2.34, 95% CI: 1.60-4.98), cigarettes smoking (OR = 6.07, 95% CI: 1.26-7.16), heavy salt intake (OR = 1.95, 95% CI: 1.27-3.23) and excessive intake of meats (OR = 1.46, 95% CI: 1.05-2.02) were risk factors for stomach cancer. CONCLUSION: Frequent eating smoked food, cigarettes smoking, heavy salt intake and over intake of meats were risk factors for stomach cancer. PMID- 11769694 TI - [A case-control study of risk factors for type 2 diabetes mellitus]. AB - OBJECTIVE: The prevalence of type 2 diabetes mellitus is increasing so to investigate the relation between insulin resistance and development of type 2 diabetes mellitus. METHODS: A 1:1 pair-matched case-control study was conducted with diagnostic criteria recommended by WHO. Controls matched with cases by age, sex, race and resident place. Information on demographic, history of disease, life-style were obtained through questionnaire. Variables including fasting blood glucose (FBG), fasting blood insulin (FBI), total cholesterol (TC), triglyceride (TG), waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR) were measured for every subject. Conditional logistics regression was used for data analysis. RESULTS: The results showed that insulin resistance, history of hypertension and waist-to-hip ratio were associated with type 2 diabetes mellitus. The values of OR were 1.530 (95% CI: 1.234-1.896), 4.833 (95% CI: 1.966-11.703), 21.996 (95% CI: 5.461-88.593), respectively. CONCLUSION: Insulin resistance was risk factor causing type 2 diabetes mellitus, independent of other risk factors. PMID- 11769695 TI - [Prevalence of dementia in Shanghai urban and rural area]. AB - OBJECTIVE: To study the prevalence and epidemiological characteristics of dementia and their major types in people aged 55 years and old in urban and rural area, Shanghai. METHODS: A sample with 17,018 residents aged 55 years and above from 22 urban and 14 rural communities was drawn through a stratified multiple stage cluster sampling. A door-to-door three-phase procedure was used to investigate the prevalence of dementia. In 1997 and 1998, A brief memory testing by MMSE was administered to all participants. In phase 2, those who scored below the cutoff points and four percent of those whose score was in the normal range were interviewed to identify dementia through a set of diagnostic examinations according to the DSM-IV criteria. In phase 3, a follow-up program was conducted in 1998 for all persons who was involved in phase 2 to identify those with Alzheimer's dementia (AD) and vascular dementia (VaD) by NINCDS-ADRDA and NINDS AIREN criteria. RESULTS: Of the targeted sample, 15,910 (94.2%) were interviewed. The overall prevalence of dementia was 3.0% in individuals aged 55 years and above, 4.32% in those aged 65 years old and 5.29% in those aged 70 years and above. The age-adjusted prevalence rates of dementia were 2.03%, 3.78% and 5.48% respectively among the age groups mentioned above. For AD the age-adjusted prevalence rates were 1.37%, 2.71% and 4.13% for individuals in above age groups. Of all types of dementia, AD was accounted 72%, followed by VaD the second. The prevalence of AD was 1.41% in man comparing to 2.78% in woman. The age-specific prevalence of AD increased with age. CONCLUSION: The prevalence of dementia was 3.0% in individuals aged 55 years in urban and rural areas in Shanghai. Alzheimer's disease was more frequent than VaD. PMID- 11769696 TI - [A diagnosis test of stress fracture during basic training set of new military recruits]. AB - OBJECTIVE: To evaluate efficacy of stress fracture (SF) during basic training for military recruits using clinical diagnosis method. METHODS: Two hundred and eighty-eight suspected SF were checked clinically and with bone scanning as golden standard. RESULTS: Sensitivity, specificity, accuracy, positive and negative predictive value, positive and negative likelihood ratios and Youden's index of clinical diagnosis were found to be 97.5%, 61.7%, 91.7%, 92.9%, 82.9%, 2.55, 0.04 and 0.59 respectively when calculated with cases. The agreement rate between two physicians was 81.7% with kappa value 0.64. When calculated with position, the precious measures were 97.2%, 84.1%, 89.7%, 82.0%, 97.6%, 6.12, 0.03, and 0.81 respectively. The agreement rate between two physicians was 94.4% with kappa value 0.88. CONCLUSION: Efficacy reliability and agreement of clinical diagnosis for SF seemed to be satisfactory. PMID- 11769697 TI - [Study of the association between human papillomavirus infection and cervical cancer in Xianguan county, Shanxi province]. AB - OBJECTIVE: To investigate human papillomavirus (HPV) prevalence in the high incidence areas of cervical cancer in Shanxi and to study the association between HPV infection and cervical cancer. METHODS: Cells exfoliated from cervix (collected by clinician) and from vagina (collected by subject herself) of 1997 women aged 35-45 from Xiangyuan county, Shanxi province were analyzed blindly by Hybrid Capture Assay (HC-II), which could detect 13 HPV types of high-risk. Unconditional logistics regression model was used to analyze the relation between HPV and cervical cancer/cervical intraepithelial neoplasia (CIN). Kappa coefficient was used to compare the agreement of the two tests. RESULTS: HPV DNA detection rate in the population was 20.8% while HPV infection rates increased with the seriousness of cervical lesions (chi 2 = 444.04, P = 0.000). Rates of the two groups (35-39 and 40-45) had no significant difference (20.9%: 20.6%, chi 2 = 0.03, P = 0.86). Unconditional logistic regression analysis showed, when comparing with the normal subjects, the risk odds ratio of HPV infection with cervical cancer/high grade CIN and low grade CIN were 254.2 and 26.4 respectively, with attributable risk proportions (ARP) 98.1% and 83.6% respectively. The sensitivity of self-collected vaginal swabs assayed for HPV DNA was lower than that of clinician-collected cervical samples assayed for HPV DNA (84%: 98%, chi 2 = 5.92, P = 0.015). No significant difference in specificity was seen between them (86%: 85%, chi 2 = 0.00, P = 0.997) and there was fair agreement between the two tests (kappa = 0.74). CONCLUSION: High-risk HPV infection in female genital tract was the major risk factor of cervical cancer and CIN in the areas. Prevention and control of cervical cancer should be focused on avoiding HPV infection, screening women for HPV infection and monitoring population infected by high-risk HPV. Self-collected vaginal swabs assayed for HPV DNA seemed a more practical method in primary screening for cervical cancer. PMID- 11769698 TI - [A case-control study of endogenous estrogen and risk of Alzheimer's disease]. AB - OBJECTIVE: To investigate the risk of Alzheimer's disease (AD) associated with endogenous estrogen. METHODS: A population based, m: n matched case-control study was conducted, including 115 female AD patients identified from sample population aged 55 years or older as cases and 1,041 non-cognitive impairment individuals from same population matched for age and sex as controls. RESULTS: Age at natural menopause had significant effect on AD using multivariate analysis. The odds ratio (OR) for AD was 0.672 for individuals whose age at natural menopause were between 47 to 50 years old, compared with individuals whose age at menopause were less than 47 years old. The OR was 0.452 for individuals whose age at menopause were more than 50 years old comparing with individuals whose age at menopause were less than 47 years old (P = 0.0207). The OR for AD increased parallel to the increase of age at menarche (adjusted OR = 1.160 for each increased year, P = 0.0342). CONCLUSION: The decrease of endogenous level in postmenopausal women might serve an etiological factor for AD. PMID- 11769699 TI - [The Rsa I and Sma I polymorphisms in the von Willebrand factor gene discrimination by hybridization with oligonucleotide arrays]. AB - OBJECTIVE: To develop a new assay for the Rsa I and Sma I polymorphisms (single nucleotide polymorphism, SNP) in the von Willebrand factor gene detection that utilizes oligonucleotide arrays (DNA chips) on glass supports. Expoloring the association of the RsaI and SmaI polymorphisms in the von Willebrand factor gene with thrombosis in Chinese. METHODS: Allele-specific oligonucleotides are covalently immobilized on glutaradehyde derivatized glass slides in arrays. Single strand PCR product of PCR-amplified genomic DNA is fluorescently labeled by assymetric PCR with fluorescently tagged dUTP and hybridized to the support bound oligonucleotide array. The hybridization pattern is detected by fluorescence scenning. The effect of hybridization conditions were evaluated and optimized. The method was validated by the discrimination of blinded DNA samples identified by restriction enzymes. 50 patients with thrombosis were examined by this method. RESULTS: The genotypes scored by oligonucleotide arrays assay were in 100% agreement with restriction enzymes results. The genotype distributions GG, GA, AA and CC, CT, TT of RsaI and SmaI polymorphisms of patients or controls were 4.0%, 12.0%, 84.0% and 24.0%, 44.0%, 32.0% or 1.4%, 11.8%, 86.8% and 8.8%, 57.4%, 33.8%. The allele frequencies G, A and C, T were 10.0%, 90.0% and 46.0%, 54.0% or 7.4%, 92.6% and 37.5%, 62.5%. No statistical difference in genotype distribution and allele frequencies was observed between patients with thrombosis and the control groups (all P > 0.05). CONCLUSION: A rapid and accurate method for the RsaI and SmaI polymorphisms in the von Willebrand factor gene detection, or for the analysis of single nucleotide polymorphism (SNP) has been developed using oligonucleotide arrays on glass supports. No association was observed between the Rsa I and Sma I polymorphisms in the vWF gene and thrombotic disease. PMID- 11769700 TI - [Study on the replication of hepatitis B virus compared with that of duck hepatitis B virus in primary duck hepatocytes]. AB - OBJECTIVE: By studying the replication of Hepatitis B virus (HBV) compared with that of Duck Hepatitis B virus (DHBV) in primary duck hepatocytes (PDH), we want to explore the host-specific regulating roles on the replication of HBV in hepatocytes from heterologous species. METHODS: PDH were transfected with complete HBV genome by electroporation (transfected group, 1.19 x 10(12) copies of linear HBV DNA/1 x 10(7) PDH) or infected with DHBV (infected group, 4 x 10(8) virions/1 x 10(7) PDH). 1, 3 and 5 days after transfection or infection, HBsAg, HBeAg and DHBsAg in the supernatant and lysate of PDH were measured with IMX System or ELISA. Meanwhile, replicative intermediates of HBV DNA and DHBV DNA were analyzed by Southern blotting and dot blotting. PDH electroporated only was used as control group. RESULTS: HBsAg in the lysates of transfected group were 15.24 (1 day), 14.55 (3 days) and 5.13 (5 days; P/N values, positive > or = 2.1), HBeAg all was negative (< 2.1), and both were negative in the supernatants of transfected group. DHBsAg in the supernatants of infected group were 14.6 (1 day), 31.53 (3 days) and 34.73(5 days; S/N values, positive > or = 2.1). Dot blotting revealed that both the total amount of HBV DNA in the transfected group and DHBV DNA in the infected group were strongly positive, whereas that of the control group was negative. Southern blot analysis of intracellular total DNA indicated that there are relaxed circular (RC), covalently closed circular (ccc) and single-stranded (SS) HBV DNA replicative intermediates in the transfected group, there was no integrated HBV DNA in the cellular genome, as the same as that of DHBV DNA in the infected group. Control groups were negative at all. CONCLUSION: Our results demonstrate that expression of HBV genes and production can occur in hepatocytes from nonmammalian species and strongly support the idea that HBV replication has no critical species-specificity, and yet hepatic specific regulating factors could be essential for viral replication. PMID- 11769701 TI - [A prospective study on the association between underweight and mortality from all cause]. AB - OBJECTIVE: To explore the association between underweight and mortality from all cause. METHOD: We examined the relationship of underweight and mortality among subjects who participated in the survey of cardiovascular risk factors (in 1984 1986 and in 1992). Relative Risks (RRs) were estimated from the COX proportional hazard model by using a BMI between 18.5-24.9 kg/m2 as reference category. RESULTS: During an average 12.40 years follow-up, we documented 307 deaths of which 158 were from cancer, 93 from cardiovascular diseases, and 56 from other causes. We observed a L-shaped relation between BMI and overall mortality. (P for trend < 0.01); In multivariated analyses, we found that the RR of mortality for a BMI of < 18.5 kg/m2 was 1.58 (95% CI 1.16-2.14) as compared with the risk among subjects with BMI of 18.5-24.9 kg/m2. The RR of overall mortality among subjects with BMI of < 18.5 kg/m2 was still significant after the exclusion of subjects who died from cancers during the first five years follow-up. CONCLUSION: Total mortality was increased among underweight people, and this association can not been completely explained by smoking and early deaths from cancer. PMID- 11769702 TI - [The etiology and clinical characteristics of central diabetes insipidus, a retrospective study of 408 cases]. AB - OBJECTIVE: To study the etiology and clinical characteristics of central diabetes insipidus (CDI). METHODS: The clinical data of 408 cases with CDI treated in Peking Union Medical College Hospital between 1956 and 2000, including 113 cases caused by tumors in sella region, were analyzed retrospectively. Follow-up for three months to 16 years was made to 35 cases of CDI without etiological diagnosis during the first visit. RESULTS: Most of the cases among children and youngsters fell ill at the age of 8-12 years, while most of the adult cases fell ill at the age of 25-35 years. Idiopathic CDI accounted for 52%. CDI caused by tumor in sella region accounted for about 33% among the child and youngster cases, among which germinoma made up about 65%. CDI caused by tumor in sella region accounted for about 22% in adult cases. Trauma-induced CDI accounted for 11% among adult cases, and about 5% among child and youngster cases. All the CDI cases caused by histiocytosis X, accounting for 3%, were children. A correct diagnosis was made within the period of two years' follow-up among 86% of the cases. For those with brain tumors, the long-term survival rate reached 80% with radiotherapy and/or operation performed without delay. CONCLUSION: GH deficiency accompanied with growth failure is a potential indicator of CDI caused by space occupying lesion in sella region. A sudden alleviation of polydipsia may indicate the dysfunction of adrenal cortex. MRI is the most valuable examination means for tumor in sella region. Regular clinical follow-up with serial brain MRI may discover the covert tumor in sella region in cases diagnosed originally as idiopathic CDI. The cases without a correct diagnosis during the first visit should be followed-up every 3 to 6 months. The prognosis of the patients with CDI without tumor is satisfactory after ADH replacement. Radiotherapy is the most effective treatment of germinoma in sella region. PMID- 11769703 TI - [Association between polymorphism of alpha 1-antichymotrypsin and apolipoprotein E gene and Parkinson's disease in Shanghai Hans]. AB - OBJECTIVE: To explore the relationship between polymorphism of alpha 1 antichymotrypsin(AACT) and apolipoprotein E(ApoE) genes and the risk of Parkinson's disease(PD) in Shanghai Hans. METHODS: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to study the distribution of AACT and ApoE gene polymorphism in 64 PD cases and 101 healthy elderly persons as controls. Association analysis was performed using odds ratio (OR) and chi 2 test. RESULTS: No difference in distribution of AACT A/T allele polymorphism was found between PD cases and healthy controls(chi 2 = 0.83 P = 0.363 > 0.05), but AACT-AA genotype was associated with PD(OR = 2.68, chi 2 = 4.31 P = 0.038 < 0.05). The ApoE gene polymorphism was not associated with PD(allele: chi 2 = 2.85 P = 0.241 > 0.05; genotype: chi 2 = 9.25 P = 0.099 > 0.05). The AACT-AT genotype frequency in PD patients was significantly lower than that in the controls without ApoE epsilon 4 allele(OR = 0.47, chi 2 = 4.10 P = 0.043 < 0.05). In AACT-AT genotype the ApoE epsilon 4 allele was associated with PD(OR = 3.26, chi 2 = 5.53 P = 0.019 < 0.05). CONCLUSION: The AACT-AA genotype and AACT-AT genotype with ApoE epsilon 4 might be susceptible factors for PD in Shanghai Hans. PMID- 11769704 TI - [Treatment of pleural effusion caused by lung carcinoma with circular intrapleural hyperthermic perfusion and its mechanism]. AB - OBJECTIVE: To assess the comprehensive effectiveness of intrapleural hyperthermic perfusion in treatment of malignant pleural effusion (MPE) caused by lung carcinoma and to explore its nechanism. METHODS: 45 patients with MPE caused by lung carcinoma underwent circular intrapleural hyperthermic perfusion with 43 warmed normal saline for 60 minutes. Response of pleural effusion and the original lung tumor, sife-effects, life qualty and survival time of the patients were followed up. Flow cytometry, optical microscopy, electron microscopy, and TUNEL method were used to compare the cytology and biochemistry of pleural effusion and cancer cells planted to the surface of pleura before and after the therapy. RESULTS: The control rate of pleural effusion was 100% (CR 93.3%, PR 6.7%). No recurrence of pleural effusion was observed in 44 cases. Pleural effusion reoccured 12 months after the thermotherapy in one case. The time without pleural effusion lasted 16.5 months on average with the longest time of 40 months. CT performed one month after the thermotherapy in 13 cases showed that the primary focus in lung dwindled in 13 cases, and remained unchanged in 5 cases. Neither operative death nor post-operative complication was found. The life quality was improved in all the cases. The medium survival time was 16.8 months. One-year survival rate was 87%. One case survived more than 3 years, 4 cases survives more than 2 years (29, 30, 31, and 40 months respectively). Carcinoembryonic antigen decreased to normal and no carcinoma cell was found in pleural effusion. Flow cytometry showed that the tumor heteroploid peak diasappeared. Pyknosis and disintegration of nuclei, and apoptotic bodies of tumor cells planted on the surface of pleura were found by optical and electron microscopy. TUNEL showed apoptotic cells with brilliant yellow fluorescence. CONCLUSION: (1) Circular intrapleural hyperthermic perfusion is a new, safe, and effective treatment for MPE. (2) Apoptosis-mediated cytocidal function, improvement of body immunity after hyperthermic perfusion and continuous wash of the perfusion fluid are important mechanisms of intrapleural hyperthermic perfusion in treatment of MPE caused by lung carcinoma. PMID- 11769705 TI - [Value of 18F-fluorodeoxyglucose positron emission tomography imaging in staging of non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the accuracy and value of fluorine desoxy-glucose Positron emission tomography (FDG PET) imaging in the staging of non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of 82 patients with NSCLC confirmed by pathological examination was made to study the staging of whole-body FDG PET scanning compared with computerized tomography (CT). RESULTS: The intake of FDG increased in the lung and metastatic foci among all 82 NSCLC patients. Whole-body PET scanning showed concentrated FDG in the 41 NSCLC patients with extrathoracic metastasis. The sensitivity and specificity of FDG PET in prediction of metastasis of mediastinal lymph nodes in patients with lung cancer were 94.4% and 100% respectively. The accuracy of PET scanning in staging of NSCLC was 95.2% in 42 patients who underwent operation after PET imaging. 37 NSCLC patients (45.1%) were restaged after the whole-body FDG PET scanning and their treatment programs were changed. CONCLUSION: PET is more advantageous in pre-operational staging of NSCLC than other conventional imaging techniques, such as CT. For accurate positioning, PET should be combined with anatomical imaging techniques. PMID- 11769706 TI - [Study on the exercise test in young health men]. AB - OBJECTIVE: To define the reaction of the respiration and circulation; and to find methods to quantitatively evaluation dyspnea and evaluate the methods that determine anaerobic threshold(AT) with the healthy man during exercise. METHODS: Exercise test was used for 43 healthy young man to measure the index of gas metabolism and artery potassium. The relation between the index of Borg scale (BS) and the oxygen uptake per minute (VO2) was observed. The methods of how to obtain anaerobic threshold(AT) were evaluated by the five kinds of gas metabolism. RESULTS: (1) VD/VT were significantly decreased from the rest to the maximal load exercise (0.28 +/- 0.55 vs 0.19 +/- 0.55, P < 0.01). (2) Seran potassium is state of after exercise (3.76 mmol/Lvs +/- 0.29 mmol/Lvs 4.10 mmol/L +/- 0.38 mmol/L, P < 0.01). (3) BS were closely correlated with VO2 during exercise, From the linear regression line 3 variables Borg scale slop(BSS), Threshold load of dyspnea(TLD), and breakpoint load of dyspnea (BLD), could be derived for quantitative evaluation of dyspnea. (4) ATVCO2 were1208 ml/min +/- 233 ml/min, and it were consistent with ATVE and ATVEO2 (P > 0.05). CONCLUSION: The artery potassium is increased after exercise in young health men. The methods of quantrta-tive evaluation of dyspnea can be used during exercise. It is suitable for AT to obtained by the sharp turning point of the carbon dioxide production (VCO2), minute ventilation (VE) and Ventilation equivalent oxygen (VEO2). PMID- 11769707 TI - [Surgical treatment of DeBakey type I and II aortic dissection]. AB - OBJECTIVE: Aortic dissection is associated with significant mortality and morbidity. Effective methods to treat aortic disection are now available although these lesions still challenge the cardiovascular surgeon. METHODS: From January 1994 to January 2000. 131 patients with DeBakey I, II type aortic dissection underwent surgical treatment. Operations were performed under cardiopulmonary bypass in 59 patients. Hypothermic circulatory arrest was used in 15 patients. Hypothermic circulatory arrest and selective cerebral perfusion was used in 57 patients. A graft replacement of ascending aorta and partial aortic arch was performed in 25 patients, ascending aorta and total aortic arch in 10. 83 patients underwent the Bentall procedure. The Bentall procedure and total aortic arch replacement were performed in 3 patients, the Wheats operation in 4. 4 patients underwent the elephant trunk techniques and 2 patients with the elephant trunk techniques and the Bentall procedures. RESULTS: There were 4 deaths within 30 days after surgery with an operative mortality of 3.05%, and 3 neurological dysfunction undergone hypothermic circulatory arrest. They were recovered within 1 week. CONCLUSION: The operative technique is difficult. Selective cerebral perfusion can provide available protection during surgery of aortic dissection. It prolongs the time allowed to performed the aortic repair. PMID- 11769708 TI - [Characterisation of transient outward potassium current (Ito1) in hypertrophied right ventricular myocytes from children with tetralogy of Fallot]. AB - OBJECTIVE: To investigate whether a transient outward potassium current exists in children hypertrophy ventricular myocytes and to characterize its basic electrophysiological properties. METHODS: Currents were recorded using whole-cell patch-clamp technique from enzymatically isolated ventricualr myocytes obtained from hearts of 10 patients aged 0.4-5 with tetralogy of Fallot (F4) ranging in age 0.4-5 years. RESULTS: In almost all cells studied, a Ito1 could be recorded on depolarization to between -20(-)+60 mV under conditions in which Ca2+ current was blocked. The current density is 4.7 PA/PF +/- 0.6 PA/PF at 60 mV. Its inactivation time constants under tested potential 0, 20, 40, 60 mV were 123 ms +/- 6 ms, 131 ms +/- 11 ms, 122 ms +/- 6 ms, 122 ms +/- 6 ms Half-maximal activation occurred at 4.1 mV +/- 2.8 mV. Half-maximal steady-state inactivation was -41 mV +/- 4 mV. Recovery from inactivation was voltage-dependent and the time course was 83 ms +/- 4 ms. CONCLUSION: A moderate Ca(2+)-independent transient outward K+ current is present in hypertrophied human ventricular myocytes from children with tetralogy of Fallot, its basic characteritics are similar to Ito1 observed in other species and human atria. PMID- 11769709 TI - [Inhibition effects of octreotide on the growth of hepatocellular carcinoma in vitro and in vivo]. AB - OBJECTIVE: To investigate the effects of somatostatin analogue octreotide on the proliferation and apoptosis of human hepatocellular carcinoma (HCC) cell line as well as the growth of HCC xenografts in nude mice. METHODS: The effects of octreotide on the proliferation and apoptosis of SMMC-7721 HCC cells was measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end labeling assay (TUNEL) or flow cytometric assay separately. Nude mice bearing xenografts of the cell line were treated with octreotide or saline as a control daily until eight weeks after tumor implantation. RESULTS: Incubation with octreotide decreased 3H-thymidine incorporation into DNA of SMMC-7721 cells by approximately 50% at a concentration of 1 mumol/L. The inhibit effect of octreotide showed a concentration dependence. After 96 h incubation, total cell count was decreased 52.2% compared with control. When cells were treated by octreotide at 1 x 10(-6) mol/L for 24 hours, the apoptosis rates was (15.2 +/- 2.4)%. At necropsy, in mice given octreotide, the mean tumor weight were significantly lower than that of control group (0.27 +/- 0.05 vs 0.85 +/- 0.37, P < 0.01). The inhibition rate of tumor in vivo at 2 months was 68.2%. CONCLUSION: Octreotide is effective in inhibiting growth of HCC both in vivo and in vitro significantly. The mechanisms of antineoplastic effect action may involved in inhibiting DNA synthesize and inducing apoptosis of tumor cells. PMID- 11769710 TI - [Investigation on the mechanism of discogenic groin pain]. AB - OBJECTIVE: To investigate the mechanism of discogenic groin pain. METHODS: Twenty one adult wistar rats were divided into experimental group (paravertebral sympathetic trunks were reserved), control group (paravertebral sympathetic trunks were resected) and self-control group (right paravertebral sympathetic trunks were resected, the left ones were reserved) randomly. Each group has 7 rats. Horseradish peroxidase (HRP) were injected into the L5-L6 intervertebral discs from right postero-lateral side. Bilateral L1, L2 spinal ganglia were sectioned after 48 hours to observe the HRP labeled cells and the effect of resection of paravertebral sympathetic trunks. Another 7 adult wistar rats were used. The same steps of injection, removal and section as in experimental group were taken. Combining method of HRP retrograde tracer with immunocytochemistry stained the sections to determine the nature of HRP labeled cells. RESULTS: HRP labeled cells were found in bilateral L1, L2 spinal ganglia in each group. The comparison results of labeled cells numbers between groups (experimental group from 22.5 +/- 7.1 to 29.3 +/- 9.7, control group from 12.9 +/- 5.1 to 13.3 +/- 4.9, P < 0.01) and of self-control group (left 24.8 +/- 6.7, 30.6 +/- 8.4, right 15.8 +/- 4.4, 14.5 +/- 4.1, P < 0.01) show that the numbers of HRP labeled cells were significantly less than that after resection of paravertebral sympathetic trunks. HRP and SP double-labeled cells can be recognized in bilateral L1, L2 spinal ganglia in immunocytochemistry experiment. CONCLUSIONS: Discogenic groin pain is referred pain which is transmitted by sympathetic nerves and appears in the area that was segmentally innervated by anterior rami of L1 and L, spinal nerves. PMID- 11769711 TI - [Microsurgical anatomy of intracranial segment of facial nerve]. AB - OBJECTIVE: To study the microsurgical anatomy of intracranial segment of facial nerve so as to provide anatomic parameters for clinical operation. METHODS: Ten adult cadavers were fixed and perfused with color silicon. Facial nerves of these cadavers were observed and measured under operative microscope according to lateral cranial base operative approach. Ten dry skulls were dissected to observe the relationships of osseous structures. The anatomic relationship and data of different segment of facial nerve were obtained respectively. RESULTS: The facial nerve was divided into five segments, namely, cerebellopontine angle segment, internal acoustic meatus segment, labyrinthine segment, tympanum segment and mastoid segment. The cerebellopontine angle segment and internal acoustic meatus segment paralleled the vestibulocochlear nerve. The labyrinthine aegment is the finest and shortest with the lebgth of 3.8 mm +/- 0.7 mm. The tympanum segment is closely related with osseous labyrinth. The mastoid segment, 15.5 mm +/- 1.9 mm long, leaves the cranium from stylomastoid foramen. CONCLUSION: Facial nerve can be located with choroid plexus of the fourth ventricle in retrosigmoid approach. Arcuate eminence and greater superficial petrosal nerve are important mark to locate internal acoustic meatus segment and labyrinthine segment in antepetrosal approach. Tympanum segment may be exposed on the surface of petrous bone in some cases. The line between lateral semicircular canals and crista of digastric muscle is the mark of mastoid segment. PMID- 11769712 TI - [The resistance of Helicobacter pylori toward metronidazole and clarithromycin]. PMID- 11769713 TI - [Strengthening the studies on acute exacerbation of chronic obstructive pulmonary disease]. PMID- 11769714 TI - [Genetic polymorphism of polyacrylamide gel electrophoresis loci in patients after non-myeloablative allogeneic peripheral blood stem cell transplantation]. AB - OBJECTIVE: To understand the information of donor and recipient in the mixed hematopoietic chimerism after non-myeloablative allogeneic peripheral blood stem cell transplantation(NM-APBSCT). METHODS: DNA samples were extracted with phenol/chloroform method and were amplified by PCR technique in heparin-blood or heparin-bone-marrow. The PCR products were analyzed using polyacrylamide gel electrophoresis and silver staining means. RESULTS: The amplified fragment length polymorphism was found in the short tandem repeat loci of 10 healthy persons and 8 leukemia patients who were not treated with hematopoietic stem cells transplantation; the bands of silver staining originated from donors and recipients were found in 3 patients after NM-APBSCT, but the brightness in the bands of donor and recipient was different. CONCLUSION: Polymorphism for mixed hematopoietic chimerism can be estimated timely, sensitively and exactly; and the results may be used to guide adoptive immunotherapy for patients after NM-APBSCT. The silver means were simple without contamination of isotopes and without using special equipment. The methods may benefit common hospitals to develop work in this respect. PMID- 11769715 TI - [Antisense oligodeoxynucleotide of telomerase gene enhances cisplatin-induced apoptosis in acute myeloid leukemia and chronic myeloid leukemia cells]. AB - OBJECTIVE: To explore the effect of human telomerase reverse transcriptase(hTERT) gene antisense oligodeoxynucleotide (ASODN) on cisplatin-induced apoptosis in cultured primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells. METHODS: Cell surviving fraction was determined using the trypan blue dye exclusion assay. Apoptosis was detected by DNA gel electrophoresis and flow cytomertric cell cycle analysis. RESULTS: Treatment with cisplatin after 24 hours of exposure of the cells to ASODN significantly reduced the number of viable AML and CML cells. However, there was no difference on AML and CML cells survival between those treated with sense oligodeoxynucleotide (SODN)/cisplatin combination and cisplatin alone. Agarose gel electrophoresis of genomic DNA from the blasts of AML and CML treated with ASODN and cisplatin combination for 72 hours showed typical DNA "ladder", but DNA from AML or CML cells treated with SODN plus cisplatin or cisplatin alone did not. The percentage of apoptotic AML and CML cells treated with cisplatin for 48 or 72 hours after 24 hours of exposure to ASODN (42.68%, 35.72%) was significantly different with that of apoptotic cells treated with SODN plus cisplatin (29.02%, 23.84%) or cisplatin alone (27.53%, 21.02%). CONCLUSION: hTERT ASODN could enhance the cisplatin induced apoptosis of AML and CML cells. PMID- 11769717 TI - [Cytokine networks and their endogenous modulators in patients with congestive heart failure]. AB - OBJECTIVE: To explore the pathophysiological role of cytokine network and their endogenous modulators in the development of congestive heart failure (CHF). METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6(IL-6), soluble TNF receptor I (sTNF-RI) and transforming growth factor (TGF) beta were measured by enzyme-linked immunoassay in 52 CHF patients with various degrees of heart failure and in 30 healthy controls. RESULTS: Patients with CHF had increased plasma concentrations of TNF alpha, IL-6 and sTNF-RI, but decreased levels of TGF-beta. They also had elevated ratios of TNF-alpha/sTNF-RI and TNF alpha/TGF-beta, particularly those in functional class IV. The levels of TNF alpha were positively correlated with IL-6 and sTNF-RI but negatively correlated with TGF-beta(P < 0.01). CONCLUSIONS: The imbalance in the cytokine network were most pronounced in patients with the most severe heart failure. CHF may be accompanied by a shift toward enhanced levels of inflammatory cytokines combined with inadequately raised or even decreased levels of anti-inflammatory cytokines. A poorly regulated cytokine network may be involved in the development and progression of CHF. PMID- 11769716 TI - [The expression of human telomerase reverse transcriptase gene in cord blood hematopoietic stem cells and its significance]. AB - OBJECTIVE: To investigate the expression and significance of human telomerase reverse transcriptase (hTERT) gene in cord blood hematopoietic stem cells. METHODS: Using in situ hybridization techniques, we detect the expression of hTERT gene in cord blood hematopoietic stem cells in different condition during different culture time. RESULTS: hTERT gene was lowly expressed in freshly isolated cord blood CD34+ cells; the positive rate was 13%. It could be increased in 5-7 days when the cells were cultured in vitro, especially in the presence of stem cell factor, interleukin-3(IL-3), IL-6 and Flt-3 Ligand together; the positive rate reached 48%. Transform growth factor-beta 1 and all-trans retinoic acid could repress hTERT gene. CONCLUSION: hTERT gene was lowly expressed in the cord blood CD34+ cells; it could be upregulated in the culture in vitro along with optimal cytokines, but was downregulated by negative regulator and induction differentiation. PMID- 11769718 TI - [Percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy: immediately and middle-term follow-up results]. AB - OBJECTIVE: To evaluate the immediate and follow-up results of percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS: 15 patients with HOCM refractory to medication successfully underwent PTSMA under myocardial contrast echocardiography. RESULTS: The left ventricular outflow gradients (LVOTG) were reduced significantly (77.93 +/- 22.00) mm Hg to (14.8 +/- 15.0) mm Hg (P < 0.0001) immediately with a mean decrease of (5.75 +/- 2.87) mm Hg (P < 0.001) in left ventricular end diastolic pressure. The scores of SAM and mitral regurgition During a mean of 8.6 +/- 3.8(6-22) months follow-up, the patients heart function (NYHA) were greatly improved(3.4 +/- 0.5 vs 1.1 +/- 0.4, P < 0.001), and disappearance of angina pectoris, and exercise endurance improvement with steady hemodynamic improvement. CONCLUSION: PTSMA is effectively non-surgical treatment method for drug-refractory patients with HOCM. PMID- 11769719 TI - [Clinical characteristics and diagnosis of chronic intestinal pseudo obstruction]. AB - OBJECTIVE: To analyze and determine the clinical characteristics and diagnostic methods of chronic intestinal pseudo-obstruction(CIP). METHODS: We reviewed the medical records of all 23 patients who diagnosed with CIP in Peking Union Medical College Hospital from 1978 to 2000. RESULTS: Twenty three patients fulfilled the diagnostic criteria (9 male, 14 female, median age 50 years, range 4-75 years). The main symptoms at the presentation were abdominal distension(87%), pain(57%), diarrhea(65%), constipation(48%), vomiting(39%) and weight loss(83%). In this group of CIP patients, the abdominal distension was more common and serious than pain, presenting with diarrhea, weight loss and dismotility in esophagus and stomach. Bowel loops and visible peristaltic waves were seldom observed in the CIP patients. The plain film showed the multiple air-fluid levels (17/20, 85%) and generalized intestinal distention and air in colon. The abnormal findings on the barium contrast examination included intestinal dilation (19/23, 83%), weaken peristalses or/and prolongation of transit time (74%) without mechanical lesions. The pseudo-obstruction involved the small intestine (83%) and colon (39%) that determined according to the radiographic features, abnormal gastrointestinal motor functions, findings of endoscopic examination and laparotomy. Eighteen cases were chronic idiopathic intestinal pseudo-obstruction (1 familial myopathy), 5 were secondary to CTD. CONCLUSIONS: Comparison with the typical mechanical obstruction, the presentations of CIP have some relatively characteristics. The clinical diagnosis of CIP can be confirmed on the basis of typical clinical symptoms and radiographic features, abnormal gastrointestinal motility. PMID- 11769720 TI - [Role of endogenous cholinergic nerve in esophageal dysmotility with reflux esophagitis]. AB - OBJECTIVE: To study the role of endogenous cholinergic nerve in esophageal dysmotility with reflux esophagitis in a feline model. METHODS: In 16 healthy cats under ketamine anesthesia (20 mg/kg), the abdominal parts of lower esophageal sphincter were cut open to establish the animal model for reflux esophagitis; esophageal motility was measured respectively preoperation and post esophagitis. The activities of choline acetyltransferase (CHAT) and acetylcholinesterase(ACHE) in medial and distal esophageal body muscle was measured respectively with spectrophotometry, and compared to the normal cats(n = 8). RESULTS: Reflux esophagitis can make distal esophageal peristaltic amplitude decrease, the distal esophageal peristaltic amplitude of cats with reflux esophagitis [above LES 1 cm: (22.65 +/- 16.53) mm Hg; above LES 3 cm:(39.94 +/- 14.78) mm Hg, P < 0.0001] was significantly lower than that of normal cats [above LES 1 cm: (63.71 +/- 21.34) mm Hg; above LES 3 cm: (73.65 +/- 23.42) mm Hg] and the conducting velocity of distal esophagus was slower than that of normal cats [(1.04 +/- 0.36) cm/s vs (1.39 +/- 0.46) cm/s, P < 0.05]. In the esophagus of reflux esophagitis group, CHAT activity was lower in the model, especially in the distal part [(81.01 +/- 22.03) U/g vs (230.13 +/- 30.10) U/g, P < 0.0001] and ACHE activity remains unchanged. CONCLUSION: CHAT activity and pressure level were lower in the distal esophagus with reflux esophagitis compared to the normal cats. This study supported that reflux esophagitis can results in dysmotility of the distal esophagus and the abnormality of endogenous cholinergic innervation is one of the important mechanisms as far as the disorder of esophageal movement in reflux esophagitis. PMID- 11769721 TI - [Genetic epidemiology and HLA survey of primary hemochromatosis among Chinese Miao ethnic]. AB - OBJECTIVE: To evaluate the inheritance modes and the genetic factors of primary hemochromatosis on its etiology among throngs of Chinese Miao nationality in causing the disease and to study the relation between the relevant susceptible gene and HLA linkage. METHODS: To investigate of the genetic epidemiology among some throngs of pure Miao nationality in western Human and the neighbouring areas was carried out and analysis of identical HLA haplotype and Lods was made. RESULTS: The population morbidity of this disease in this area is 0.48%. Twenty four patients found in four families had high plasma glucose levels, and apparently high serum total iron and serum transferrin. The prevalence of hemochromatosis was 44.45% by analysis on the first degree and second degree relatives of the 24 patients. The individual marking of HLA ranges from locus A1, A2 to A3. CONCLUSION: HLA haplotype shows obvious deviation from random distribution, which indicates that there exists linkage between HH pathogenic gene and HLA. The results of genetic analysis in this disease group suggest that hemochromatosis is an autosomal dominant inheritance but not autosomal recessive inheritance disease. PMID- 11769722 TI - [Expression of cell adhesion molecule (CD44V6) in thyroid tumors and its significance]. AB - OBJECTIVE: To investigate the expression of the cell adhesion molecule (CD44V6) in thyroid tumor tissue and its relationship with the pathogenesis, development, invasiveness and metastasis of the tumor. METHODS: Immunohistochemistry was applied to examine the expression of CD44V6 in 20 specimens of tissue adjacent to carcinoma, 24 of thyroid adenoma and 64 of thyroid carcinoma (including 30 papillary carcinoma, 26 follicular carcinoma, 2 anaplastic carcinoma and 6 medullary carcinoma). All the specimens were paraffin-embedded. RESULTS: The expression of CD44V6 was observed in 14 specimens of adenomas(58.33%), and 59 of carcinoma (92.19%), but was not detected in the tissue adjacent to carcinoma. The expression of CD44V6 was significantly different between follicular epithelial carcinoma and medullary carcinoma (96.55% vs 50.0%, P < 0.01). The frequency of overexpression of CD44V6 was associated with both invasiveness and lymph node metastasis (P < 0.01), but it had no relation with age, sex and tumor size (P > 0.05). CONCLUSION: It is suggested that CD44V6 will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for local invasion and lymph node metastasis of thyroid carcinoma. PMID- 11769723 TI - [An analysis of the clinical and pathological characteristics of mu-tong (a Chinese herb) induced tubulointerstitial nephropathy]. AB - OBJECTIVES: To investigate the clinical and pathological characteristics of Mutong (a Chinese herb, caulis aristolochiae manshuriensis) induced tubulointerstitial nephropathy (MT-TIN), and analyze the related to renal function decline and clinical prognosis. METHODS: 51 patients with MT-TIN were studied retrospectively. They were divided into acute, mild chronic and severe chronic groups according to the pathological lesion. Clinical and pathological data were semi-quantitatively assessed. Correlation and regression of the parameters were further tested. Relationship between medication and the illness, incidence, clinical characteristics, therapy and regression of the disease were analyzed. The results of the acute group of MT-TIN were compared with those of the antibiotics-induced acute tubular necrosis (A-ATN) and acute interstitial nephritis (A-AIN). RESULTS: The common clinical symptoms of MT-TIN were fatigue, polyuria, nocturia, usually accompanied by renal tubular dysfunction with or without an elevated serum creatinine (Scr) level. It was rare to find urine abnormality and anemia in the acute and mild chronic groups. The pathological examination of MT-TIN revealed that there were severe degradation, necrosis and collapse of the renal epithelial cells leaving the basement membrane naked. Regeneration was rarely seen as in A-ATN. Cellular infiltrate in the interstitium was also rarely seen as in A-AIN. However, marked tubular atrophy and early occurrence of diffuse interstitial fibrosis were detected in the chronic groups. Correlation and regression tests showed that the level of Scr correlates obviously with the degree of anemia and renal interstitial fibrosis. After withdrawal of medication containing MT, most patients' Scr level became steady within 2 months. Both the clinical and pathological characteristics were different with those of A-ATN or A-AIN. Most of the patients suffering from MT TIN got the disease by over-dose or long-term taking of medicines containing Mu Tong. Few patients had it when taking regular dose of the medicine. CONCLUSION: MT-TIN is a special type of drug-induced tubulointerstitial nephropathy, which is mainly related to over-dose or long-term taking of Mu-Tong, which contains aristolochic acid. One should try to avoid using Mu-Tong containing aristolochic acid and pay attention to monitor the renal function if the medication has to be given. PMID- 11769724 TI - [Apolipoprotein E 4 gene is a risk factor for Alzheimer's disease]. AB - OBJECTIVE: To study the association of Alzheimer disease (AD) with apolipoprotein E (ApoE) epsilon 4 allele and to find the biological peripheral markers for the laboratory diagnosis of AD. METHODS: 107 patients with AD, 68 patients with vascular dementia (VD) and 74 sex- and age-matched non-demented healthy individuals (NDC) were collected. DNA from patients and healthy individuals was extracted from peripheral blood samples with the phenol-chloroform procedure and ApoE was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The frequency of epsilon 4 was significantly higher in AD than that in VD and NDC and there was no difference in the frequency of epsilon 4 between VD and NDC. The age at onset of the disease in the group carrying two epsilon 4 alleles was significantly younger than that in the group with one epsilon 4 allele in AD. Moreover, in comparison with AD patients without epsilon 4 allele, the age at onset in the group with one epsilon 4 allele was younger. Patients with epsilon 4 or without epsilon 4 allele in VD patients did not differ significantly in age at onset. Meanwhile, 3 familial AD cases were found, all carrying epsilon 4 allele. CONCLUSION: AD and ApoE4 were closely related. ApoE epsilon 4 was a dangerous factor of AD and ApoE 4 allele made contribution to the heterogenicity of AD. PMID- 11769725 TI - [Clinicopathological analysis of 6 cases of diffuse panbronchiolitis]. AB - OBJECTIVE: To study the clinical and pathological characteristics of diffuse panbronchiolitis (DPB). METHODS: Clinical history of six cases of DPB and their pathological slides were studied and analyzed. RESULTS: Diffuse panbronchiolitis was characterized by chronic recurrent nasosinusitis and pulmonary infection and respiratory bronchiolitis. Pathologically, all layers of the respiratory bronchiole walls were involved. Prominent chronic inflammation with lymphocytes, plasma cells and histiocytes infiltration was noted in all cases. In the lumens of the bronchioles, PMN or mucus could be identified. The chronic inflammatory cell infiltration also contained numerous foamy macrophages within the walls of the small bronchioles and in the stroma of the lung as well. Among the 6 cases of DPB, two cases were associated with thymoma. CONCLUSIONS: DPB is a distinct clinicopathological entity. Open lung biopsy or thorocoscopic biopsy is necessary for the correct diagnosis of clinical atypical DPB cases. PMID- 11769726 TI - [Clinicopathologic features and prognosis of lymphoepithelioma-like carcinoma of the lung]. AB - OBJECTIVE: To analyze the clinicopathologic features and prognosis of lymphoepithelioma-like carcinoma (LELC) of the lung. METHODS: 26 cases of pulmonary LELC with available long-term follow-up information were compared with 84 cases of pulmonary non-LELC(33 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 6 cases of adeno-squamous carcinoma and 9 cases of large cell carcinoma) with available long-term follow-up information using Kaplan-Meier method and the generalized Wilcoxon test. RESULTS: LELC of the lung had a better prognosis than non-LELC (P < 0.05). Further study showed that pulmonary LELC had a significantly better prognosis than adeno-squamous carcinoma and large cell carcinoma. However, there was no significant prognostic differences between pulmonary LELC and squamous cell carcinoma and adenocarcinoma. Tumor recurrence and necrosis (> or = 5% of tumor) were associated with poor prognosis. CONCLUSION: Pulmonary LELC, which is a very rare and unique entity, has a better prognosis after therapy. PMID- 11769727 TI - [Comparison and analysis of clinicopathology of lung cancer between 1980s and 1990s in the Shenyang area (1,224 cases)]. AB - OBJECTIVE: To compare the changes in pathogenetis and histopathology of lung cancer between 1980s and 1990s in the Shenyang area. METHODS: The HE stained sections of 572 cases of lung cancer from 1981-1990 and 652 cases from 1991-2000 were reviewed. Parts of these samples were also studied with immunohistochemistry and in situ hybridization. RESULTS AND CONCLUSIONS: By comparing the finding in the 1980s and those of the 1990s, it was found that (1) the incidence of lung cancer in women increased. (2) the highest incidence occurred in the 61 to 70 year of old group in 1990s, in 1980s it was 51-60 years. (3) there was an increased incidence of adenocarcinoma, especially papillary adenocarcinoma and acinar adenocarcinoma and bronchioloalveolar carcinoma in the 1990s. PMID- 11769728 TI - [Human telomerase RNA (hTR) expression in lung cancer in the Gejiu and Xuanwei regions of Yunnan]. AB - OBJECTIVE: To investigate the correlation between the expression of hTR in and the pathogenesis of lung cancer in Gejiu and Xuanwei regions of Yunnan province. METHODS: By use of in situ hybridization, the expression of hTR gene was observed in 81 cases of lung cancer tissues including 24 cases of Gejiu Tin miners (GTM), 36 cases of Xuanwei farmers (XF) and 21 cases of other regions. RESULTS: hTR was detected in 65.4% (53/81) of the lung cancer cases. The positive rate of hTR in GTM, XF and other regions was 66.7% (16/24), 58.3% (21/36) and 76.2% (16/21) respectively. Positive hTR expression was not found in normal bronchial and alveolar epithelia, but was found in highly proliferating type II alveolar epithelial cells adjacent to the carcinoma (12.3%, 10/81). No significant difference was observed with regard to the positive rate of hTR expression among three different regions. There was no statistically significant correlation between the expression of hTR, the patients' sex, age and the differentiation degree of the tumor, but the expression of hTR was correlated with histological type and lymph node metastasis (P < 0.05). CONCLUSION: The expression of hTR is a prevailing event in lung cancer and therefore can be used as an indicator of lung malignancy. PMID- 11769729 TI - [Clinicopathological and molecular genetic analysis in Chinese typical hereditary nonpolyposis colorectal cancer pedigrees]. AB - OBJECTIVE: To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. METHODS: Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues from 4 probands showed high level of microsatellite instability at more than 2 loci(RER + phenotype). Three of 4 cases lost hMSH2 protein expression and one case showed no hMLH1 protein expression. Three pathological germline mutations (2 on hMSH2 and 1 on hMLH1) were identified. CONCLUSIONS: Chinese typical HNPCC kindreds showed relatively frequent germline mutations of mismatch repair genes. Microsatellite instability analysis and immunohistochemistry staining might be the effective screening methods before direct DNA sequencing for the detection of mismatch repair genes. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC kindreds. PMID- 11769730 TI - [Multivariate analysis of the parameters related to prognosis of astrocytoma]. AB - OBJECTIVE: To investigate the clinical and pathological characteristics of astrocytoma and the factors related to pathologic gradings as well as prognosis in astrocytoma. METHODS: 120 cases of the astrocytoma with complete clinical data were selected as the study group, of which 94 cases had follow-up data. 20 cases of normal brain tissue and demyelinating plaques with astrocyte hyperplasia were used as the control group. The expression of Ki-67, VEGF, collagen IV and TRT by immunohistochemical staining and detection of TRTmRNA and telomerase RNA by in situ hybridization were studied. RESULTS: (1) Both astrocytoma and demyelinating lesions showed various positivity for Ki-67. The difference between different gradings of the astrocytoma and non-neoplastic lesions were significant(P < 0.01). Taking 8.5% of Ki-67 expression as threshold, there was significant difference between two survival curves indicating favorable and unfavorable prognosis in the tumor group respectively (P < 0.01). (2) Microvascular changes, such as the density of blood vessels, did not demonstrate any difference between grade I, II astrocytoma and normal tissue, but was significantly increased in grade III and IV astrocytoma and even more in the necrotic area (P < 0.01). The expression of VEGF correlated closely to the density of the blood vessel (P < 0.01). (3) The expression of TRT protein was negative in normal astrocytes but positive in proliferative disease and astrocytoma. The intensity of the positivity was enhanced by the grading of the tumor and correlated with the prognosis (P < 0.01). The expression of hTR, TRTmRNA was less than that of TRT but was well correlated to TRT expression. CONCLUSIONS: Use of the cox-regression model in multivariate analysis shows that there are six parameters closely related to the prognosis of astrocytoma, of which the pathological grade being the most critical factor. Ratio of Ki-67 positivity, age of patient, duration of symptoms are also important factors, while microcystic changes in the tumor and expression of VEGF are independent favorable factors for astrocytoma. PMID- 11769731 TI - [Expression of ADAM12 (Meltrin-alpha) gene in giant cell tumor of bone]. AB - OBJECTIVE: To detect expression and location of ADAM12 (meltrin-alpha) gene in giant cell tumor of bone and to study its effect on the formation of multinucleated giant cells in the tumor. METHODS: ADAM12 mRNA was detected by RT PCR and RNA in situ hybridization in 18 cases of giant cell tumors, 6 cases of cultured tumor cells, 2 specimens of embryonic muscle tissue and 5 specimens of adult muscle tissue. RESULTS: RT-PCR showed that 12/18 (67%) cases of giant cell tumor of bone expressed ADAM12 mRNA. RNA in situ hybridization demonstrated positive ADAM12 mRNA in 12 cases of the detected tumors. The ADAM 12 mRNA positive signal was localized in the cytoplasm of almost all multinucleated giant cells and mononuclear stromal cells. However, the expression of ADAM12 mRNA decreased gradually, and eventually lost with increased passages of tumor cells and the disappearance of multinucleated giant cells in the culture. CONCLUSION: Multinucleated giant cells probably originated from the fusion of mononuclear stromal cells and ADAM12 may participate in the fusion process. PMID- 11769732 TI - [Study on the rat airway epithelial cell injury induced by bacterial infection and its pathogenesis]. AB - OBJECTIVE: To explore the rat airway, especially small airway epithelium injury induced by Klebsiella pneumoniae infection and its pathogenesis. METHODS: A rat airway inflammation and COPD model was induced by repeated intranasal infection with Klebsiella pneumoniae. The injury changes were dynamically observed under SEM, TEM and LM. Actin, TNF-alpha, Fos, Jun protein and their mRNA expression levels in small airway epithelium were analyzed by immunohistochemistry and in situ hybridization. The changes of lung TNF-alpha content were examined by radioimmunoassay. RESULTS: 1 week after Klebsiella pneumoniae infection the epithelial cilia cohered, fell down, partially fell off and the tight intercellular connection destroyed. 2 and 4 weeks after the infection, the injury of bronchus epithelia worsened with pronounced chronic inflammation in all bronchi. The bronchioles walls became thickened, lumen narrowed and emphysema was noted. Compared with control group, TNF-alpha mRNA expression was higher (P < 0.01) in the 2nd and 4th week while TNF-alpha protein was higher at 4 weeks (P < 0.01). From 1st week after the infection, Fos protein and mRNA expression began to elevate (P < 0.01). TNF-alpha content of lung began to increase (P < 0.01) and kept at a higher level until the 8th week. CONCLUSIONS: Repeated intranasal injection of a certain amount of Klebsiella pneumoniae can induce airway inflammation and emphysema. The main features of early airway epithelia injury are damage of cilia and intercellular junctions, the cause of which may be associated with changes in microfilament arrangement of epithelia. High expression of TNF-alpha protein in the airway epithelia and lung parallels with epithelium injury. Fos and Jun proteins may also play important roles in up regulating the TNF-alpha protein. PMID- 11769733 TI - [Antisense RNA for urokinase receptor inhibits the invasiveness and metastasis of lung carcinoma]. AB - OBJECTIVE: To inhibit invasion and metastasis of human lung carcinoma cell line 95D by antisense RNA for urokinase receptor (uPAR). METHODS: Antisense RNA expression plasmid for uPAR was introduced into the highly metastatic human lung carcinoma cells 95D. Modified Boyden's chamber was used to detect the invasion ability, and nude mice were used to determine metastasis. RESULTS: Two transfected clones were found to integrate the antisense expression plasmid into genomic DNA and to express antisense RNA for uPAR. Antisense RNA blocked the uPAR expression in the transfected clones. The evident reductions of the invasiveness of antisense clones were observed by comparison with control cells, 95D cells and cells transfected with pcDNA3 vector. The metastatic potential of these two antisense clones decreased significantly in comparison with the controls (P < 0.05). CONCLUSIONS: The results suggest that antisense RNA for uPAR inhibits uPAR expression and leads to a decrease of metastatic potential of 95D cells. Antisense RNA technique may have a valuable application in anti-metastatic therapy of human lung carcinoma. PMID- 11769734 TI - [Influence of fluid shear stress on the expression of monocyte chemotactic protein-1 by vascular endothelial cells]. AB - OBJECTIVE: To study the effect of fluid shear stress on the expression of monocyte chemotactic protein-1(MCP-1) by vascular endothelial cells and its role in the early stages of atherogenesis(AS). METHODS: Parallel plate flow chamber was used to expose vascular endothelial cells to different shear stress. Sandwich ELISA (enzyme-linked immunosorbent assay) and RT-PCR (reverse transcription polymerase chain reaction) were applied to detect MCP-1 protein and mRNA respectively. RESULTS: Under 0.72 Pa shear stress, MCP-1 mRNA expression in endothelial cells reached a high level in 5 hours, but decreased to below the control level (P < 0.001) after 12 hours. The expression of MCP-1 mRNA showed a time dependent increase, which became slower 5 hours later. When different shear stress (0.30, 0.72, 2.40 Pa) was loaded for the same period of time (5 h), MCP-1 increased to above twice the control level, while its mRNA expression increased threefold as compared to the static control. CONCLUSIONS: The expression of MCP-1 reacts strongly to fluid shear stress. The steady laminar flow down regulates the gene expression of MCP-1. These results may help to explain why AS lesions tends to occur at the site of turbulent blood flow. PMID- 11769735 TI - [Study of the mechanisms of pulmonary fibrosis in recent years]. PMID- 11769736 TI - [The study on Kail, a tumor metastasis suppressor gene]. PMID- 11769737 TI - [Research advance of primary cutaneous B cell lymphoma]. PMID- 11769738 TI - [Non-approved antidotes in Japan--Foreign antidotes imported for poisoning countermeasures at the Summit 2000]. PMID- 11769739 TI - Late onset white matter disease in peroxisome biogenesis disorder. AB - OBJECTIVE: To report late onset cerebral white matter disease as a distinctive phenotype in peroxisome biogenesis disorder (PBD). BACKGROUND: There is phenotypic and genetic overlap among the PBD known as Zellweger syndrome (ZS), infantile Refsum disease (IRD), and neonatal adrenoleukodystrophy (NALD). Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy. In a structured follow up cohort of 25 patients with PBD, not including ZS, three patients had an unusual pattern of cerebral white matter disease with onset past the age of 1, not conforming to any of the classic PBD phenotypes. METHODS: Clinical phenotyping and follow-up, peroxisomal biochemical determinations in body fluids and fibroblasts, identification of affected PEX gene by genetic complementation in fibroblasts, and MRI studies. RESULTS: Two unrelated patients with PBD without distinctive external features had normal neurodevelopmental milestones during their first year, followed by rapid deterioration including severe hypotonic pareses, seizures, retinopathy, and deafness. A third patient initially diagnosed with IRD developed cerebral white matter degeneration in the third year of life, complicating the original diagnosis. MRI in all three patients showed cerebral demyelination with sparing of subcortical fibers and pronounced central cerebellar demyelination. CONCLUSIONS: Late-onset cerebral white matter disease may occur in PBD, either following IRD or following normal early development and in the absence of distinctive external features. Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease PMID- 11769740 TI - [Edmund Wojtyla (1906-1932), doctor in the Public Hospital in Bielsko: victim of profession]. AB - Edmund Wojtyla was born on 27 July 1906 in Krakow. He passed the examination for the secondary-school certificate in 1924 in Wadowice and in 1930 he graduated in medicine from the Medical Faculty of Jagiellonian University. In 1931 he began work as a physician in the State Hospital in Bielsko. He caught scarlet fever from a female patient and died on 4 December 1932. Edmund Wojtyla was the older brother of Pope John Paul II. PMID- 11769741 TI - [Medicine in Soviet gulags]. AB - The origins of healthcare in gulags were associated with ideological paradigms. The fact that could support this hypothesis is that gulags were aimed at the physical destruction of enemies of the Bolshevik state and system. In this case, the economical aspect of healthcare was of a secondary importance. In every gulag, there was so called sanitary unit (sanchast) equipped with a barrack (called stationary), where a physician or surgeon's assistant (lepkom) worked with his staff. The physician was partially independent of the gulag authorities. He could release a certain number of prisoners from work, change a prisoner is health category, assign better food or admit a prisoner to the stationary barrack which commonly contained a few beds inside, to OP barrack (with better food) or to hospital. The physician also took part in so called medical committees which assigned various health categories to prisoners. Gulag hospitals included camp, regional and central hospitals. Their therapeutic profile depended on the commonest gulag diseases (there were surgical, tuberculosis, venereal, general and psychiatric profiled hospitals). The staff of gulag healthcare was recruited from among former and current prisoners. Their attitude to patients, as those who shared their misery, was usually very benevolent. Despite the permanent lack of pharmaceuticals, equipment and the primitive life conditions, a prisoner admitted for stationary therapy usually lay in a normal bed, with clean bed-clothes, received better food, all created of which on illusion of well-being and gave some hope for survival. PMID- 11769742 TI - [Albertinum: Koenigsberger university]. PMID- 11769743 TI - Performance indicators from all perspectives. PMID- 11769744 TI - Indicators without a cause. Reflections on the development and use of indicators in health care from a public health perspective. AB - Indicators have a long history in public health. Since the end of the 18th century information on the health of communities has been gathered on a health system level and public health indicators have become more sophisticated over the vears. However, in many modern health care systems there is a separation between public health and health services. This paper discusses the need for integration and promotes a stronger public health orientation of health services. This has consequences for the nature of indicators on the health services level. The methodological problems of turning epidemiological data into management information for health services are discussed. The key message is that the health of the community should be the ultimate cause of all indicators. PMID- 11769745 TI - Measuring quality: from the system to the provider. AB - The literature on quality has often focused on process indicators. In this paper we outline a framework for describing and measuring the quality of health systems in terms of a set of desirable outcomes. We illustrate how it can be measured using data collected from a recent evaluation of health system performance conducted by the World Health Organization (WHO). We then explore the extent to which this framework can be used to measure quality for all components of the system; for example, regions, districts, hospitals, and providers. There are advantages and disadvantages to defining quality in terms of outcomes rather than process indicators. The advantage is that it focuses the attention of policy makers on whether systems are achieving the desired goals. In fact, without the ability to measure outcomes it is not possible to be sure that process changes actually improve attainment of socially desired goals. The disadvantage is that measuring outcomes at all levels of the system poses some problems particularly related to the sample sizes necessary to measure outcomes. WHO is exploring this, initially in relation to hospitals. The paper discusses two major challenges. The first is the question of attribution, deciding what part of the outcome is due to the component of the system under discussion. The second is the question of timing, including all the effects of current health actions now and in the future. PMID- 11769746 TI - Performance measurement for ambulatory care: moving towards a new agenda. AB - Despite a shift in care delivery from inpatient to ambulatory care, performance measurement efforts for the different levels in ambulatory care settings such as individual physicians, individual clinics and physician organizations have not been widely instituted in the United States (U.S.). The Health Plan Employer Data and Information Set (HEDIS), the most widely used performance measurement set in the U.S., includes a number of measures that evaluate preventive and chronic care provided in ambulatory care facilities. While HEDIS has made important contributions to the tracking of ambulatory care quality, it is becoming increasingly apparent that the measurement set could be improved by providing quality of care information at the levels of greatest interest to consumers and purchasers of care, namely for individual physicians, clinics and physician organizations. This article focuses on the improvement opportunities for quality performance measurement systems in ambulatory care. Specific challenges to creating a sustainable performance measurement system at the level of physician organizations, such as defining the purpose of the system, the accountability logic, information and reporting needs and mechanisms for sustainable implementation, are discussed. PMID- 11769747 TI - Improving performance using indicators. Recent experiences in the United States, the United Kingdom, and Australia. AB - This article describes recent national performance improvement initiatives in the United States, United Kingdom, and Australia. This comparison is of particular interest because each of these three countries faces similar challenges in delivering health care and improving health. Each has elevated a focus on safety and quality improvement to a national level. Marked differences in the organization and financing of health care across these three countries provide a unique opportunity to compare and contrast approaches. Drawing on the experience of the authors in each of the three countries and publicly available data sources about specific national initiatives, we describe the national context for improvement and outline recent performance improvement initiatives and emerging issues and challenges. Similarities and differences in the current evolution of national performance initiatives are described and conclusions are drawn about challenges that all three countries face, particularly in terms of developing meaningful sets of national indicators of health system performance. The challenges for future work include the importance of information infrastructure, the paucity of accurate and accessible clinical data, the need for effective performance measurement processes at a local level to capture useful data, and the tensions of balancing accountability and improvement agendas for measurement. PMID- 11769748 TI - Seeking consumer views: what use are results of hospital patient satisfaction surveys? AB - There has been increasing emphasis on the use of patient satisfaction surveys in publicly funded health services to assess elements of quality of care. However, how these surveys are used to change policy and services has received less attention. This paper reports on two different surveys conducted in Victoria, Australia and how these have developed and been used at a policy level. One is a survey of recent mothers, repeated three times over the course of the decade. The other is an inpatient survey developed over the past 5 years. The results of the surveys are publicly available and arc one means of obtaining consumer views, influencing health care quality and reporting to the public. PMID- 11769749 TI - The advantages and disadvantages of process-based measures of health care quality. AB - As consumers, payers, and regulatory agencies require evidence regarding health care qualities the demand for process of care measures will grow. Although outcome measures of quality represent the desired end results of health care, validated process of care measures provide an important additional element to quality improvement efforts, as they illuminate exactly which provider actions could be changed to improve patient outcomes. In this essay, we discuss the advantages and disadvantages of process measures of quality, and outline some practical strategies and issues in implementing them. PMID- 11769750 TI - Process versus outcome indicators in the assessment of quality of health care. AB - This paper reviews the relative strengths and weaknesses of outcome and process measures as performance indicators in health care. Differences in outcome may be due to case mix, how the data were collected, chance, or quality of care. Health care is only one determinant of health and other factors have important effects on health outcomes, such as nutrition, environment, lifestyle and poverty. The advantages of process measures are that they are more sensitive to differences in the quality of care and they are direct measures of quality. However, outcome measures are of greater intrinsic interest and can reflect all aspects of care, including those that are otherwise difficult to measure such as technical expertise and operator skill. Outcome indicators can be improved if efforts are made to standardize data collection and case mix adjustment systems are developed and validated. It is argued that this is worth doing only where it is likely that variations in health care might lead to significant variations in health outcome and where the occurrence of the outcome is sufficiently common that the outcome indicator will have the power to detect real differences in quality. If these conditions are not met, then alternative strategies such as process measurement and risk management techniques may be more effective at protecting the public from poor quality care. PMID- 11769751 TI - Statistical issues in reporting quality data: small samples and casemix variation. AB - PURPOSE: To present two key statistical issues that arise in analysis and reporting of quality data. SUMMARY: Casemix variation is relevant to quality reporting when the units being measured have differing distributions of patient characteristics that also affect the quality outcome. When this is the case, adjustment using stratification or regression may be appropriate. Such adjustments may be controversial when the patient characteristic does not have an obvious relationship to the outcome. Stratified reporting poses problems for sample size and reporting format, but may be useful when casemix effects vary across units. Although there are no absolute standards of reliability, high reliabilities (interunit F > or = 10 or reliability > or = 0.9) are desirable for distinguishing above- and below-average units. When small or unequal sample sizes complicate reporting, precision may be improved using indirect estimation techniques that incorporate auxiliary information, and 'shrinkage' estimation can help to summarize the strength of evidence about units with small samples. CONCLUSIONS: With broader understanding of casemix adjustment and methods for analyzing small samples, quality data can be analysed and reported more accurately. PMID- 11769752 TI - From a process of care to a measure: the development and testing of a quality indicator. AB - This paper outlines the steps in developing and implementing process measures of quality. Developing a process measure includes defining the purpose of and audiences for the measures, choosing the clinical area to evaluate, organizing the assessment team, choosing the component of the process to measure, writing the indicator specifications, performing preliminary tests of feasibility, reliability and validity, and determining scoring and analytical specifications. Given the growing evidence in the literature regarding the impact of care, and an evolving understanding of how to develop and implement process of care measures as outlined here, the future should bring the development and implementation of quality indicators that are rigorously developed and that will provide insights into opportunities to improve the quality of care. PMID- 11769753 TI - Ethical principles in the counseling of gay and lesbian adolescents: issues of autonomy, competence, and confidentiality. AB - Ethical dilemmas in counseling gay and lesbian adolescents are analyzed according to underlying ethical principles. Developmental issues and their relevance to therapy are emphasized. Conflicts among client autonomy, claims of paternalism, and limits of confidentiality are examined. Competence to enter therapy for issues of sexual identity is assessed. The author concludes that adolescents are generally competent to explore issues of sexual identity. PMID- 11769754 TI - Ethics of treatment and research in psychiatry. AB - Most of the publications in the year under review have centered around dilemmas, particularly ethical problems in clinical practice. It has not, however, been a period of systematic theoretical work. In this review, a range of dilemmas which arise in clinical practice are discussed. PMID- 11769755 TI - Killing and letting die: "Intentional killing is prohibited. So is the presumption of evil intent". PMID- 11769756 TI - Words and contraception. PMID- 11769757 TI - Heart and soul: the case of the conjoined twins. PMID- 11769758 TI - Ethical issues in cybermedicine. PMID- 11769759 TI - Euthanasia, morality, and law. Transcript. PMID- 11769760 TI - The law of above averages: leveling the new genetic enhancement playing field. PMID- 11769761 TI - Unnecessary adversaries at the end of life: mediating end-of-life treatment disputes to prevent erosion of physician-patient relationships. PMID- 11769762 TI - Prevention of HIV/AIDS among injection drug users: the theory and science of public health and criminal justice approaches to disease prevention. PMID- 11769763 TI - Measuring the prevalence of Mycobacterium tuberculosis resistance is not that easy: the interest and limits of a retrospective survey. PMID- 11769764 TI - Should tuberculosis programmes invest in second-line treatments for multidrug resistant tuberculosis (MDR-TB)? PMID- 11769765 TI - Revisiting the death of Eleanor Roosevelt: was the diagnosis of tuberculosis missed? AB - Controversy has surrounded the death of Eleanor Roosevelt in 1962. There has been a persistent sense that doctors missed the diagnosis of miliary tuberculosis, thereby jeopardizing her life. This article, using Roosevelt's medical chart and other previously unreviewed documents, revisits her illness and death. What disease actually killed Eleanor Roosevelt? Did her physicians miss the diagnosis? These questions are of particular importance in light of the recent Institute of Medicine report estimating that almost 100,000 Americans die each year from medical mistakes. Why has the possibility of error clouded the care of Roosevelt for almost 40 years? What can Roosevelt's case reveal about ongoing efforts to reduce mistakes in clinical practice? PMID- 11769766 TI - Idiopathic interstitial pneumonias: a re-appraisal of idiopathic pulmonary fibrosis. AB - Over the last 30 years the clinical and histopathological definitions of the diffuse lung diseases have evolved considerably. Initially pathological entities were defined in parallel with clinico-radiological diagnoses, but these have more recently become consolidated into a more meaningful combined classification. These refinements have impacted on the diffuse lung diseases in particular, and have defined individual diseases more precisely than in previous classifications in which a number of distinct entities had been grouped together and mistaken for idiopathic pulmonary fibrosis, resulting in much confusion. The American Thoracic and European Respiratory Societies' committees, charged with the task of defining the idiopathic interstitial pneumonias, have recently published a statement on idiopathic pulmonary fibrosis, and a statement on the other idiopathic interstitial pneumonias should follow this year. Of these diseases, idiopathic pulmonary fibrosis is the most lethal, and this review deals with the impact that the changes in the nomenclature will have on our understanding of this and the other diseases with which idiopathic pulmonary fibrosis was previously confused and explores the implications of our new understanding on clinical practice. It also attempts to highlight areas of previous dogma in the literature that now need to be re-considered in the context of these more recent statements. PMID- 11769767 TI - Economic analysis of tuberculosis diagnostic tests in disease control: how can it be modelled and what additional information is needed? AB - As the goal of tuberculosis (TB) control programmes is to get as many cases as possible onto correct treatment, the critical role of diagnosis is obvious. Under diagnosis contributes to further spread of the disease, while over-diagnosis wastes scarce resources on inappropriate treatment. Various techniques are available with which to diagnose TB, including sputum smear microscopy, chest X ray, antibiotics and culture. While it may be possible to improve the application of these diagnostic tools, there is universal recognition of their limitations. Although new technologies have been developed, their appropriateness for use in resource-poor settings has been questioned due to concerns associated with their complexity and high cost. Given the constrained resources of most countries heavily affected by TB, economic evaluation provides a powerful tool to facilitate the prioritisation of resources. However, economic appraisals of diagnostic procedures provide several unique methodological challenges, including specification of appropriate alternatives, measuring costs, and measuring outcomes. Nevertheless, the use of decision analytic models can provide an opportunity to explore many of these issues. This paper presents key problems in the diagnostic process, reviews existing diagnostic techniques, and discusses possible improvements of these techniques and the introduction of new techniques. Next it examines the usefulness of modelling the economics of TB diagnosis, highlighting gaps in information requirements. Finally, the article identifies economic and epidemiological factors that are likely to change results in different settings. PMID- 11769768 TI - Design of regimens for treating tuberculosis in patients with HIV infection, with particular reference to sub-Saharan Africa. AB - The highest burden of human immunodeficiency virus (HIV) related tuberculosis (TB) is in sub-Saharan Africa. HIV complicates several areas of TB control, one of which involves treatment and treatment outcome. Large patient numbers cause congestion on TB wards, there is increased morbidity, an increased risk of adverse drug reactions, an increased case fatality, and an increased recurrence of TB after treatment completion. TB Control Programmes have responded to these problems by taking actions such as abolishing thioacetazone and decentralising the initial phase of treatment to peripheral health centres and the community. Despite this response, there are three major on-going concerns which need to be addressed by research studies. There is a need to reduce case fatality rates focusing on 1) stronger treatment regimens, 2) adequacy of rifampicin levels when intermittent treatment regimens are used, and 3) adjunctive treatments. There is a need to reduce recurrent rates of TB by 1) determining the relative role of re infection and reactivation as a cause of recurrence, 2) assessing the importance of duration and type of anti-TB treatment for the first episode of TB, and 3) determining the role of secondary isoniazid preventive therapy. There is a need to evaluate how best to decentralise treatment from the perspective of the health service and the patient. Research studies should be relevant to the needs and resources of TB control programmes, and should include pharmacokinetic studies, controlled clinical trials and operational research, including economic analysis and social science evaluation. PMID- 11769769 TI - Pattern of mycobacterial resistance to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the state of Qatar after the implementation of DOTS and a limited expatriate screening programme. AB - OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the State of Qatar after the implementation of DOTS and an expatriate screening programme on arrival. METHOD: A state-wide, population-based, retrospective analysis of all cases of pulmonary tuberculosis with positive M. tuberculosis culture reported to the Division of Public Health TB Unit from January 1996 to December 1998. M. tuberculosis sensitivity testing was done by the Bactec method for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). The results were interpreted as a daily change of the growth index of test vials (with drug) compared with controls. RESULTS: There were 406 isolates with positive M. tuberculosis culture. Sixty-one (15%) were resistant to one or more of the four anti-tuberculosis drugs, of which 58 (95%) were from newly diagnosed cases (primary) and three (5%) were from previously treated cases (acquired). Primary resistance was as follows: any resistance 15%, INH 12.4%, RMP 2%, SM 5.2%, EMB 0.8% and multidrug resistance (MDR, resistance to INH and RMP at least) was found in 0.8%. Acquired resistance was as follows: any resistance 15%, INH 15%, RMP 5%, SM 5% and MDR 5%. CONCLUSION: The prevalence of resistance to four anti tuberculosis drugs is strikingly low due to the limited expatriate screening programme (chest radiography) and implementation of DOTS. The four-drug regimen is recommended for the initial phase of therapy until the results of sensitivity testing are known. PMID- 11769771 TI - Ambulatory treatment of multidrug-resistant pulmonary tuberculosis patients at a chest clinic. AB - SETTING: Retrospective cohort analysis of multidrug-resistant tuberculosis (MDR TB) patients treated at a Korean National Tuberculosis Association out-patient chest clinic. OBJECTIVE: To evaluate treatment outcomes and contributing factors. DESIGN: A review of clinical records of 1011 pulmonary MDR-TB patients retreated with individualised regimens selected on the basis of previous chemotherapy and drug susceptibility testing from 1988 to 1996. RESULTS: The patients (mean age 38.6 years) had resistant organisms to an average of 3.7 drugs and were retreated with an average of 4.2 drugs which they had previously not taken and to which they were susceptible. Treatment outcomes were as follows: 487 cases (48.2%) cured, 82 (8.1%) failed, 394 (39.0%) defaulted, 45 (4.5%) transferred out, and three (0.3%) died. The treatment efficacy among those who completed chemotherapy was 85.6%. In a multivariate analysis favourable response was significantly associated with a greater number of newly prescribed drugs in the regimen to which they were susceptible (odds ratio [OR] 3.6; 95% confidence interval [CI] 1.3-9.5), younger age (OR 2.0; 95%CI 1.1-3.9), and a lower number of drugs to which they were resistant (OR 1.8; 95%CI 1.1-3.1). The case fatality rate, including the follow-up period, was 1.7% (17 cases). CONCLUSION: The cure rate of MDR-TB patients treated at an out-patient clinic was 48.2% due to a high defaulter rate (39.0%). However, 85.6% of those who completed treatment were cured. PMID- 11769770 TI - Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States. AB - SETTING: Health care workers and medical students in the United States subject to annual tuberculin skin testing. OBJECTIVE: To use skin testing with Mycobacterium avium sensitin (MAS) to determine contemporary rates of infection with non tuberculous mycobacteria (NTM) and their effect on reactions to M. tuberculosis purified protein derivative (PPD). DESIGN: Dual skin testing was performed with PPD and MAS on 784 health care workers and medical students in the northern and southern US. MAS reactions that were > or = 5 mm and also > or = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM. RESULTS: MAS reactions were > or = 5 mm in 40% and > or = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P < 0.001). PPD reactions were > or = 15 mm in 3% of subjects. PPD reactions > or = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P < 0.001). MAS dominant reactions were found in 82% of subjects with 5-9 mm PPD reactions and 50% with 10-14 mm PPD reactions; these reactions were more common among whites (P = 0.046), US-born (P = 0.038) and subjects without BCG immunization (P = 0.004). CONCLUSIONS: Infections with NTM are responsible for the majority of 5-14 mm PPD reactions among US-born health care workers and medical students subject to annual tuberculin testing. PMID- 11769772 TI - Directly observed treatment for multidrug-resistant tuberculosis: an economic evaluation in the United States of America and South Africa. AB - OBJECTIVE: To estimate the cost-effectiveness of directly observed treatment compared to conventional therapy in reducing the spread of multidrug-resistant tuberculosis, for an industrialised country (represented by the United States of America) and a developing country (South Africa). METHODS: Monte Carlo analysis using published data on probability, cost and health impact. RESULTS: In both countries, directly observed treatment is the dominant strategy, yielding cost savings and improved health outcomes. Cost savings for directly observed treatment relative to conventional therapy become more significant as more expensive second-line drugs are used in treatments. CONCLUSIONS: The cost effectiveness of directly observed treatment relative to conventional therapy is demonstrated for both the USA and South Africa. Cost savings are more pronounced (especially for South Africa) as the likelihood of multidrug-resistant tuberculosis increases and more expensive second-line therapies are used. Given that health care resources are more severely constrained in developing countries, the data contained in this study are useful in guiding the design of policies for the effective management of multidrug-resistant tuberculosis in settings with limited resources. PMID- 11769773 TI - Clinical diagnosis of smear-negative pulmonary tuberculosis: an audit of diagnostic practice in hospitals in Malawi. AB - SETTING: Thirty-seven hospitals in Malawi. OBJECTIVE: To audit the hospital practice of clinically diagnosing adults with smear-negative pulmonary tuberculosis (PTB). DESIGN: A cross-sectional survey of adults aged 15 years or above who were registered and receiving inpatient treatment for smear-negative PTB. An assessment of each patient was carried out to determine 1) the number of recommended diagnostic guidelines (cough >3 weeks, no response to antibiotics, negative sputum smears and a chest radiograph compatible with PTB) used by hospital staff in making the diagnosis of PTB, and 2) whether the clinical diagnosis of smear-negative PTB was correct according to criteria set by the study. RESULTS: There were 259 patients, 127 men and 132 women, with a mean age of 37 years; 93% had a cough >3 weeks, 95% had received one or more courses of antibiotics, 92% had submitted sputum samples for smear examination and 97% had chest radiographs performed. In 148 (57%) patients, all four diagnostic guidelines were used, and in 238 (92%) patients three or more were used. The diagnosis of smear-negative PTB was considered correct by study criteria in 203 (78%) patients. In the remainder, 22 (8%) were considered to have extrapulmonary TB and 34 (14%) another diagnosis. CONCLUSION: Hospital practices in the diagnosis of smear-negative PTB are reasonable, although there is room for improvement with in-service training and regular audits of practice. PMID- 11769774 TI - Demographic risk factors and lymphocyte populations in patients with tuberculosis and their healthy contacts. AB - SETTING: Campania, a southern region of Italy, and the Institute of Respiratory Diseases, Monaldi Hospital, University 'Federico II', Naples. OBJECTIVE: To evaluate clinical and socio-demographic risk factors for tuberculosis (TB) infection and/or disease. Peripheral blood lymphocytes from a sub-cohort of 19 patients and 53 contacts were studied by flow cytometry. DESIGN: A prospective study among patients with newly diagnosed pulmonary tuberculosis and their close contacts. RESULTS: A total of 90 patients and 277 contacts were enrolled. The prevalence of infection was 45% (95%CI 39-51%) among contacts. Age, sex, delay in diagnosis and treatment, cavitation on chest radiograph, cough, unwillingness to cover the mouth, and volume of air shared by close contacts and patients were investigated as potential risk factors for infection. Only delay in diagnosis of cases remained independently associated with an increased risk of infection (P < 0.0002), and hemoptysis was the only factor capable of reducing the delay significantly. The CD8+ CD28+ cytotoxic subset was significantly diminished in the patients (P < 0.001), whereas the CD8+ CD28- and CD8+ CD57+ (suppressor and NK-like subsets) were elevated (P < 0.001 and P = 0.04). CONCLUSIONS: These data show that delay in diagnosis of cases is a crucial factor for tuberculosis and that cytotoxic CD8+ cells play a primary role in immune response to tuberculosis. PMID- 11769775 TI - Pyrazinamide use as a method of estimating under-reporting of tuberculosis. AB - OBJECTIVE: To develop a method of validating the notification of active tuberculosis by physicians in the Netherlands. METHOD: The chemotherapeutic agent pyrazinamide was used as a marker for the occurrence of tuberculosis. On the basis of defined daily doses (DDD) of pyrazinamide dispensed to out-patients, an estimate was made of the number of patients with tuberculosis in the Netherlands in the period 1994-1998. DDD is a technical unit of measurement and does not necessarily reflect the recommended or actual dose used. Usually it is based on the average dosage per day for the main indication in adults with normal organ function. The Dutch Drug Information Project (GIP) of the Health Care Insurance Board (CVZ) provided the DDD data. Based on the notification of tuberculosis patients to the Netherlands Tuberculosis Register (NTR) we calculated how much pyrazinamide (measured in DDDs) these patients would have used depending on their body weight. RESULTS: The number of DDDs prescribed according to the GIP pharmacy records differed by only 8% from the number of DDDs calculated on the basis of notification to the NTR; 6889 patients should have been registered instead of 6349. CONCLUSION: The close correlation between the use of pyrazinamide as measured by the GIP and NTR provides strong evidence that in the Netherlands tuberculosis is reported in conformity with the guidelines for notifiable diseases. The method was simple to apply and may deserve follow-up in other countries. PMID- 11769776 TI - Efficacy of the BCG revaccination programme in Hong Kong. PMID- 11769777 TI - Would you know one if you met one? PMID- 11769778 TI - PCR-based assays for the diagnosis of tuberculosis. PMID- 11769779 TI - Concurrent Mycobacterium tuberculosis and Mycobacterium bovis infections in a patient with AIDS. PMID- 11769780 TI - The Tuberculosis Scientific League: enrolling medical students in the battle against the disease. PMID- 11769781 TI - Using other people's graphs--what should be acknowledged? PMID- 11769782 TI - Visual problems and falls. AB - Visual impairment is a risk factor for falls, on average approximately doubling falls risk in a wide variety of studies. Falls risk increases as visual impairment worsens. The relationship is almost certainly causal. Vision accounts for perhaps a quarter to a half of all falls, although this estimate is imprecise. Visual impairment in 70% or more of elderly people is remediable with relatively simple interventions (correcting refractive errors and cataract surgery), making it an important potential target for intervention at the population level. However, no intervention has yet been proven to reduce falls risk in a randomized controlled trial. PMID- 11769783 TI - Cardiovascular causes of falls. PMID- 11769784 TI - Falls and fractures. PMID- 11769785 TI - Exercise for prevention of osteoporotic fracture. PMID- 11769786 TI - Epidemiology of falls. PMID- 11769787 TI - Effects of physical activity on postural stability. PMID- 11769788 TI - Interdisciplinary practice in the prevention of falls--a review of working models of care. PMID- 11769789 TI - Potentiometric sensor array for the determination of lysine in feed samples using multivariate calibration methods. AB - A potentiometric sensor array has been developed for the determination of lysine in feed samples. The sensor array consists of a lysine biosensor and seven ion selective electrodes for NH4+, K+, Na+, Ca2+, Mg2+, Li+, and H+, all based on all solid-state technology. The potentiometric lysine biosensor comprises a lysine oxidase membrane assembled on an NH4+ electrode. Because the selectivity of the lysine biosensor towards other cation species is not sufficient, there is severe interference with the potentiometric response. This poor selectivity can be circumvented mathematically by analysis of the richer information contained in the multi-sensor data. The sensor array takes advantage of the cross-selectivity of lysine for each electrode, which differs from the other species and quantification of lysine in complex feed sample extracts is accomplished with multivariate calibration methods, such as partial least-squares regression. The results obtained are in a reasonable agreement with those given by the standard method for amino acid analysis. PMID- 11769790 TI - Non-destructive NIR-FT-Raman analyses in practice. Part I. Analyses of plants and historic textiles. AB - Non-destructive analysis of natural substances in plants as well as of old dyed textiles by Raman spectroscopy has not been possible using conventional techniques. Exciting lines from the visible part of the spectrum produced photochemical and thermal decomposition of the objects as well as strong fluorescence. Using Nd:YAG laser excitation at 1,064 nm together with a special sample arrangement and interferometric recording, various polyacetylenes in Aethusa cynapium and in chamomile (Chamomilla recutita) and the main valuable substances in gentian species (Gentiana lutea and G. punctata), curcuma roots (Curcuma longa), cinnamon (Cinnamomum zeylanicum), fennel (Foeniculum vulgare), clove (Caryophyllus aromaticus), and ginger (Zingiber officinale) were analyzed non-destructively and discussed in comparison with the corresponding pure standard compounds. We further analyzed non-destructively the FT Raman spectra of collections of historical textiles and lakes used for dyeing. It is possible to distinguish the main dye component non-destructively by using Raman bands. PMID- 11769791 TI - Non-destructive NIR-FT-raman analyses in practice. Part II. Analyses of 'jumping' crystals, photosensitive crystals and gems. AB - Using an improved sampling arrangement we observed the FT Raman spectra of the different phases of a 'jumping crystal', an inositol derivative. The phase transition produced--as consequences of large changes of the unit cell constants- changes in frequency and intensity mainly of CH deformation vibrations. Photochemical reactions, usually produced with light quanta in the visible range, are not activated with the quanta from the Nd:YAG laser at 1064 nm. The Raman spectra of the 'dark' form of a dinitrobenzyl pyridine and afterwards the 'light' form, the product of its illumination in the visible range, were recorded. We could not observe changes of most bands, especially not of the NO2-vibrations; however, a new strong band appeared at 1253 cm(-1), which may be due to the expected NH-photo-isomer. Genuine gemstones and fakes can be unambiguously identified by FT Raman spectroscopy. This is especially useful for the stones whose physical properties are quite similar to those of diamonds--moissanite and zirconia. The quality of diamonds can be estimated from relative band intensities; however, this is not in complete agreement with the internationally accepted visual qualification. Synthetic diamonds produced by CVD (chemical vapor deposition) show remarkable differences from natural ones in their FT-Raman spectra. PMID- 11769792 TI - Determination of lead in an Sb-Pb alloy by anodic linear scan voltammetry. AB - Anodic linear scan voltammetry (ALSV) has been used to determine the content of Pb (up to 3.5 wt%) in a eutectic type of binary Sb-Pb alloy. The effect of type of electrolyte and as well as the rate of the potential change on the dissolution of Pb from this alloy were investigated by ALSV. The method can be used for the determination of low concentrations of Pb in the investigated alloy and well defined current peaks of Pb dissolution can be detected on the voltammograms. Well-de-fined linear dependencies between the quantities of electricity under the current peak of Pb dissolution (QPb) and the respective contents of Pb (w) in the alloy, so-called "check curves", were found. The smallest ratio of Pb in Sb-Pb alloy which could be detected by ALSV was 0.45 wt%. The dissolution involves only ten atomic layers of the less precious metal (Pb) from the surface of the alloy samples. PMID- 11769793 TI - Adsorption and preconcentration of 2,4-dichlorophenoxyacetic acid on a chemically modified silica gel surface. AB - The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), chemically anchored to a silica gel surface, was used to adsorb and preconcentrate the same herbicide from aqueous solutions at room temperature. From a series of adsorption isotherms adjusted to a modified Langmuir equation, the maximum number of moles adsorbed was calculated as 4.67 x 10(-5) mol g(-1), with the highest retention capacity at pH 5. This modified silica gel was used in a column for preconcentrating trace levels of 2,4-D. The preconcentrated herbicide can be directly eluted with methanol with a recovery efficiency higher than 97%. The concentration factor was 8.33. PMID- 11769794 TI - High-performance liquid chromatographic procedure for routine residue monitoring of seven sulfonamides in milk. AB - A simplified method for routine monitoring of 7 residual sulfonamides (SAs) (sulfadiazine (SDZ), sulfamerazine (SMR), sulfadimidine (SDD), sulfamonomethoxine (SMM), sulfamethoxazole (SMX), sulfadimethoxine (SDM), and sulfaquinoxaline (SQ)) in milk using high-performance liquid chromatography (HPLC) with a photodiode array detector is described. The spiked and blank samples were cleaned up by using an Ultrafree-MC/PL centrifugal ultrafiltration unit. For determination/identification, a Mightysil RP-4 GP column and a mobile phase of 25% (v/v) ethanol in water with a photodiode array detector were used. Average recoveries from milk samples spiked with 0.05, 0.1, 0.2, and 0.5 microg mL(-1) of each drug were >82%. The inter- and intra-assay variabilities were 2.0-3.1%. The practical detection limits for 7 SAs were 0.005-0.02 microg mL(-1). The total time and amount of solvent required for the analysis of one sample were <40 min and <6 mL of ethanol, respectively. No toxic solvents were used. PMID- 11769795 TI - Determination of proteins by their enhancement of resonance light scattering by fuchsine acid. AB - Based on the measurement of the enhancement of resonance light scattering (RLS) of fuchsine acid (FSA) by proteins, a novel sensitive assay of proteins in body fluid samples has been developed. Proteins, including bovine serum albumin (BSA), human serum albumin (HSA), pepsin (Pep), alpha-chymotrypsin (Chy), lysozyme (Lys), and cellulase (Cel), can bind to fuchsine acid (FSA), resulting in enhanced RLS signals at 277.0 nm. Linear relationships between the enhanced RLS intensity and the protein concentration were measured at different concentration of FSA, and the limits of detection for BSA, HSA, and Lys were found to lie in the nanogram range. PMID- 11769796 TI - Preconcentration of chromium (III) and speciation of chromium by electrothermal atomic absorption spectrometry using cellulose adsorbent. AB - A simple and sensitive method has been developed for species selective determination of chromium(III) and chromium(VI) in water by electrothermal atomic absorption spectrometry. The procedure is based on selective absorption of Cr(III) on a cellulose micro column (pH 11, 0.5 mol L(-1) NaCl). Total chromium was subsequently determined after appropriate reduction of Cr(VI) to Cr(III). Recoveries of more than 97% were found. A concentration factor of 100 was achieved. The relative standard deviations (n=10) at the 40 ng L(-1) level for chromium(III) and chromium(VI) were 2.3% and 1.8% and corresponding limits of detection (based on 36) were 1.8 ng L(-1) and 5.1 ng L(-1), respectively. No interference effects have been observed from other investigated species and the method has been successfully applied to natural water samples. PMID- 11769797 TI - An immunoassay for terbutryn using direct hapten linkage to a glutaraldehyde network on the polystyrene surface of standard microtiter plates. AB - 2-Aminobutylamino-4-ethylamino-6-isopropylamino-1,3,5-triazine (ABA-atrazine) has been synthesized and used as a coating hapten in an immunoassay with a monoclonal antibody against terbutryn. Coating was achieved by covalently linking ABA atrazine to a glutaraldehyde polymer network directly bound to the polystyrene surface of a standard 96-well microtiter plate. The assay was carefully optimized. In particular, the coating hapten concentration had a strong effect on the ELISA sensitivity. By including a pre-incubation step a low test midpoint (IC50-value) of 0.130 microg L(-1) was achieved. As far as we are aware this is the most sensitive ELISA for terbutryn yet reported. The coating-hapten-format presented is proposed as generally applicable, because the glutaraldehyde modified microtiter plate surface enables stable immobilization of a broad variety of coating haptens. PMID- 11769798 TI - Non-protected fluid room-temperature phosphorimetric procedure for the direct determination of naftopidil in biological fluids. AB - Non-protected fluid room temperature phosphorescence, NPRTP, has been applied to the determination of naftopidil in biological fluids. The proposed method is based on obtaining a phosphorescence signal from naftopidil using potassium iodide as heavy atom perturber and sodium sulfite as a deoxygenating reagent without a protected medium. Optimized conditions for the determination were 1.4 mol L= KI, 5.0 x l0(-3) mol L(-1) sodium sulfite, pH 6.5 (adjusted with sodium hydrogen phosphate-dihydrogen phosphate buffer solution, 5.0 x 10(-2) mol L(-1). The delay time, gate time, and time between flashes were 70 micros, 400 micros, and 5 ms, respectively. The maximum phosphorescence signal appeared instantly and the intensity was measured at lambda(ex)=287 nm and lambda(em)=525 nm. The response obtained was linearly dependent on concentration in the range 50 to 600 ng mL(-1). The detection limit, according to error-propagation theory, was 7.93 ng mL(-1) and the detection limit as proposed by Clayton was 11.12 ng mL(-1). The repeatability was studied by using ten solutions of 400 ng mL(-1) naftopidil; if the theory of error propagation is assumed the relative error is 0.88%. The standard deviation of replicates was found to be 3.5 ng mL(-1). This method was successfully applied to the analysis of naftopidil in human serum and urine with recoveries of 104.0 +/- 0.6% for serum and 106.0 +/- 1.0% for urine. PMID- 11769799 TI - Multielement electrothermal atomic absorption spectrometry: a study on direct and simultaneous determination of chromium and manganese in urine. AB - A study was carried out on the direct determination of Cr and Mn in urine using simultaneous atomic absorption spectrometry (SIMAAS). The heating program conditions, the absorbance signal profiles, the influence of different chemical modifiers, and the urine sample volume delivery into the tube were optimized to perform the calibration with aqueous solutions. Among several chemical modifiers tested, the best recovery and repeatability results were obtained for 3 microg Mg(NO3)2. On using this modifier, the pyrolysis and atomization temperatures for simultaneous determination of Cr and Mn were 1,300 degrees C and 2,500 degrees C, respectively. Urine samples were diluted (1+1) with 2.0% (v/v) HNO3 + 0.05% (w/v) Triton X-100 prepared in high purity water. A 20-microL aliquot of analytical solution and 10 microL of chemical modifier solution were delivered to the graphite tube. The characteristic masses were 7.8 pg for Cr (RSD=4.0%) and 4.6 pg for Mn (RSD=2.6%). The limits of detection were 0.08 microg L(-1) (n=20, 3s) for Cr and 0.16 microg L(-1) (n=20, 3s) for Mn. Recovery studies for 1.0 or 2.5 microg L(-1) of Cr and Mn added to different urine samples showed acceptable results for Cr (100%, RSD=14%) and Mn (88%, RSD=5.6%). PMID- 11769800 TI - The use of sector field ICP-mass spectrometry for Rb-Sr geochronological dating. AB - Rb-Sr dating, one of the most important tools in geochronology, requires determination of the Rb/Sr concentration ratios and the 87Sr/86Sr isotope ratios in co-genetic minerals or rocks and is traditionally performed by thermal ionization mass spectrometry (TIMS). In this work we investigated whether sector field inductively coupled plasma mass spectrometry (ICP-MS), which is characterized by a high sample throughput and straight-forward sample introduction, could be used as an alternative to TIMS. To avoid spectral overlap of the ion signals of the isobaric nuclides 87Sr and 87Rb, Sr was separated from Rb by cation-exchange chromatography. A mathematical correction was applied to take into account the small amount of Rb that can be present in the Sr fraction. The isotope ratio accuracy and precision attainable with ICP-MS were evaluated by analysis of several reference materials from the US Geological Survey. The results of this evaluation show that excellent accuracy could be achieved; the internal precision (repeatability) of the isotope ratio (expressed as the relative standard deviation for 10 successive 1-min measurements) was 0.04-0.12%. An attempt was made to calculate the total or combined uncertainty on the isotope ratio results, by also taking into account other possible error sources (corrections for mass discrimination, detector dead time, blank signal and Rb fraction). Finally, the same procedure was used for dating two rock formations that were 2,500 Ma and 350 Ma old, according to age determinations previously performed by the Rb-Sr laboratory of the University of Munchen (Germany) using TIMS. The ICP-MS results (2,520 +/- 150 Ma and 379 +/- 48 Ma) obtained for these formations compare well with the corresponding TIMS data (2,509 +/- 120 Ma and 357 +/- 25 Ma). PMID- 11769801 TI - Effect of extraction pH on metal speciation in plant root extracts. AB - The species patterns of nutrient and trace metals (K, Ca, Mg, Mn, Fe, Zn) obtained by extraction of plant roots have been determined as a function of extraction pH in the range 4-9. The extractable metal concentrations were subdivided into low-molecular-weight (<10 kDa) and high-molecular-weight (>10 kDa) metal species by TXRF analysis. Except for pH 9, the low-molecular-weight fraction is predominant. This fraction was further separated by HPLC with AAS detection. It was demonstrated that the nature of the metal species changes dramatically when the extraction pH is changed, especially in the range 9-7. Information about the chemical nature of chromatographically separated metal species is obtained by use of different electrochemical detectors (amperometric detection at a glassy carbon or copper electrode and pulsed amperometric detection) and diode-array UV detection. PMID- 11769802 TI - Speciation and oxidation kinetics of arsenic in the thermal springs of Wiesbaden spa, Germany. AB - Since 1886 arsenic has been known to be present as a trace component in the Wiesbaden thermal waters at concentrations of over 100 microg L(-1). In this study for the first time molecular level speciation of arsenic was measured both in the water (by HG-AAS) and in wellstone scale deposits (by XANES). Most of the arsenic in the anoxic NaCl-type waters is in the reduced arsenite form. Hydrous ferric oxide (HFO) precipitates in the scale deposits scavenge only the minor dissolved arsenate portion which is, however, accumulated up to 3% w/w. Isothermal precipitation experiments at in-situ temperatures showed a difference between the progress of both arsenic and iron oxidation and precipitation. This can be explained in terms of adsorption of the aqueous arsenite and heterogeneous oxidation on the HFO surface, but subsequently rapid release of the arsenate thereby formed back into the aqueous phase at enhanced temperature and increased pH. Such relatively rapid pseudo-homogeneous arsenite oxidation is too slow to efficiently retard the As(III) load already on the wellhead, but fast enough to prevent arsenic seepage into ground water aquifers. PMID- 11769803 TI - Calibration graphs for Ti, Ta and Nb in sintered tungsten carbide by infrared laser ablation inductively coupled plasma atomic emission spectrometry. AB - Infrared laser ablation (IR-LA) has been studied as a sample introduction technique for the analysis of sintered cobalt-cemented tungsten carbide materials by inductively coupled plasma atomic emission spectrometry (ICP-AES). Fractionation of cobalt was observed. Linearity of calibration plots was verified at least up to 15% Ti, 8% Ta, and 3% Nb. Above 1% (m/m) Ti, Ta, and Nb, the repeatability of results was better than 3% R.S.D. The relative uncertainty at the centroid of the calibration line was in the range from +/- 3% to +/- 4% for Ti, Ta, and Nb with internal standardization by tungsten and up to +/- 5% without internal standardization. The limits of detection were 0.004% Ti, 0.001% Ta, and 0.004% Nb. Elimination of the cemented hardmetal dissolution procedure is the main advantage of this method. PMID- 11769804 TI - Novel enzymatic assay for determination of alkyl polyglycosides with short chain fatty alcohols. AB - An enzymatic assay has been developed for the quantitative detection of alkyl polyglycosides after enzymatic hydrolysis with different carbohydrolases. A three step enzymatic method was used for the quantification of alkyl polyglycosides. In the first step the enzymatic hydrolysis of alkyl polyglycosides was performed with different carbohydrolases, or an acid hydrolysis was used. The second step was quantification of free glucose with an enzyme electrode, which was covered with an immobilized glucose oxidase membrane; glucose was used as standard. The last step was the enzymatic quantification of fatty alcohols, which are the second substrate after enzymatic hydrolysis of alkyl polyglycosides. Surprisingly, the enzyme alcohol dehydrogenase ADH (E.C. 1.1.1.1) from bakers' yeast could efficiently oxidize a wide variety of aliphatic alcohols and had the highest catalytic specificity with short and medium fatty alcohol substrates, including octanol and decanol. PMID- 11769805 TI - Critical assessment of the performance of electronic moisture analyzers for small amounts of environmental samples and biological reference materials. AB - Two electronic moisture analyzers were critically evaluated with regard to their suitability for determining moisture in small amounts (< or = 200 mg) of various environmental matrices such as leaves, needles, soil, peat, sediments, and sewage sludge, as well as various biological reference materials. To this end, several homogeneous bulk materials were prepared which were subsequently employed for the development and optimization of all analytical procedures. The key features of the moisture analyzers included a halogen or ceramic heater and an integrated balance with a resolution of 0.1 mg, which is an essential prerequisite for obtaining precise results. Oven drying of the bulk materials in a conventional oven at 105 degrees C until constant mass served as reference method. A heating temperature of 65degrees C was found to provide accurate and precise results for almost all matrices investigated. To further improve the accuracy and precision, other critical parameters such as handling of sample pans, standby temperature, and measurement delay were optimized. Because of its ponderous heating behavior, the performance of the ceramic radiator was inferior to that of the halogen heater, which produced moisture results comparable to those obtained by oven drying. The developed drying procedures were successfully applied to the fast moisture analysis (1.4-6.3 min) of certified biological reference materials of similar provenance to the investigated the bulk materials. Moisture results for 200 mg aliquots ranged from 1.4 to 7.8% and good agreement was obtained between the recommended drying procedure for the reference materials and the electronic moisture analyzers with absolute uncertainties amounting to 0.1% and 0.2-0.3%, respectively. PMID- 11769806 TI - Dynamic light scattering measurements of particle size development in aqueous humic materials. AB - Dynamic light scattering (DLS) has been used to monitor changes in aggregate sizes of aqueous humic materials as a function of solution properties. Humic and fulvic acids were dissolved at relatively low concentrations (15-30 mg L(-1)) in solutions of different temperature, cation and ethanol content, and pH. The results could be explained in terms of intramolecular contraction and intermolecular aggregation of humic polymers. The former were prevalent in soil humic acids, and less so in aquatic humic acids and fulvic acids. Increasing the temperature of humic solutions generally led to an increase in particle sizes, which was ascribed to an effect akin to surfactant clouding. The addition of cations led to either contraction or expansion, depending on the charge and concentration of the ion, and the nature of the humic material. Reducing the pH initially caused contraction, followed by growth and precipitation in more highly acidic media. PMID- 11769807 TI - Application of experimental design in a method for screening sediments for global determination of organic tin by electrothermal atomic absorption spectrometry (ETAAS). AB - An experimental design was developed to obtain a simple procedure for global determination of organic tin compounds in sediment. Sediment was extracted by a two-phase method and tin was determined in the organic extract by electrothermal atomic absorption spectrometry (ETAAS), with palladium as chemical modifier. A Plackett-Burman design for screening and a fractional central composite design (CCD) for optimizing were used for evaluation of the effects of several variables. The results showed that sediment mass, volume and concentration of extracting acid, pyrolysis and atomization temperatures, and modifier concentration affect the determination. Reference material PACS-2 was analyzed to evaluate the procedure. It was possible to extract 82% of the organotin content certified in the reference sediment. The limit of detection (LOD) was 0.08 microg g(-1) and the relative standard deviation was 4%. The method was applied to the analysis of estuarine superficial sediments from Gipuzkoa (Spain). The organotin content of these samples ranged from 0.7 to 7.7 microg g(-1), as tin, on a dry weight basis. PMID- 11769808 TI - Detection of volatile organic peroxides in indoor air. AB - A supercritical fluid extraction cell filled with adsorbent (Carbotrap and Carbotrap C) was used directly as a sampling tube to enrich volatile organic compounds in air. After sampling, the analytes were extracted by supercritical fluid CO2 with methanol as modifier. Collected organic peroxides were then determined by a RP-HPLC method developed and validated previously using post column derivatization and fluorescence detection. Some volatile organic peroxides were found in indoor air in a new car and a newly decorated kitchen in the lower microg m(-3) range. tert-Butyl perbenzoate, di-tert-butyl peroxide, and tert butylcumyl peroxide could be identified. PMID- 11769809 TI - Development of an analytical method for the simultaneous determination of 15 carcinogenic polycyclic aromatic hydrocarbons and polycyclic aromatic nitrogen heterocyclic compounds. application to diesel particulates. AB - A new method enabling the determination of 15 priority carcinogenic polyaromatic compounds (PAC) proposed by the US National Toxicology Program (NTP) has been developed and applied to diesel exhaust particulates (DEP). The clean-up procedure consists of solid-phase extraction (SPE) and HPLC fractionation on silica phases followed by liquid-liquid extraction and chromatography on a polyvinylbenzene copolymer column. The method gives good recoveries for all PAC studied except dibenzo[a,j]acridine and dibenzo[a,h]pyrene, for which recovery values are below 80%. The use of GC-MS ion trap and its capacity to achieve single-ion storage enhanced the sensitivity of the method, enabling the detection of high-molecular-weight PAH in the low ng g(-1) concentration range. Intermediate polarity GC columns, e.g. BPX-50 or equivalent, enabled better separation, when applied to DEP analysis, than the generally used DB-5 apolar phase. This is observed mainly for separation of isomeric compounds belonging to the benzofluoranthene and dibenzopyrene families. The application of this method to DEP sampled from the exhaust of a diesel engine and in confined locations such as a tunnel has shown that all PAH of the NTP list could be detected, except dibenzo[a,h]pyrene. No dibenzacridine or dibenzocarbazole could be detected in such matrices. The method is sufficiently sensitive to be applicable to environmental exposure measurements in occupational health surveys. PMID- 11769810 TI - Electrochemical reduction of chloridazon at mercury electrodes, and its analytical application. AB - The electrochemical behavior of the herbicide chloridazon, I (pyrazon), at different pH is described. The electrode reaction (one wave in acidic media and another in alkaline media), investigated using direct current and pulse voltammetry, controlled-potential coulometry, and HPLC-MS, is a combination of the electroreduction (two-electron in the first step) and a kinetic process as a result of which simple compounds (HCl, NH3) are released and, moreover, a five membered pyrrole cycle is formed in strongly acid media. Products of the kinetic reaction are further reducible. The dissociation constant of I, pKa = 2.96, was found spectrophotometrically. Fast-scan differential pulse voltammetry (FSDPV) was used for determination of I; the detection limit was 2.7 x 10(-8) mol L(-1) (0.006 microg L(-1)) at pH 2.3. Chloridazon was determined in spiked drinking and river water. PMID- 11769811 TI - Evaluation of an automated clean-up system for the isotope-dilution high resolution mass spectrometric analysis of PCB, PCDD, and PCDF in food. AB - An automated clean-up system was evaluated for the simultaneous analysis of polychiorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF), and biphenyls (PCB) in different foods. In addition to the seventeen 2,3,7,8-substituted PCDDIPCDF and four non-ortho PCB, by use of the clean-up system studied, it was possible to collect the eight mono-ortho and two di-ortho PCB and the seven indicator PCB in two separate fractions during the same clean-up run. The study was first performed using standard mixtures containing PCDD, PCDF and PCB, and a certified reference material. The recoveries of the 13C-labeled compounds ranged from 51 to 90%, indicating that the PCDD, PCDF, and PCB clean-up worked satisfactorily. Next, the automated system for PCDD, PCDF, and PCB analysis was evaluated for foods such as milk, egg, meat (beef, chicken, and pork), mussel, and olive oil. The recoveries of the 13C-labeled compounds ranged from 40 to 120% for PCB and from 57 to 113% for PCDD/ PCDF, meeting the requirements of well accepted methods. Thus, the automated clean-up system studied is a suitable alternative to conventional clean-up methods. PMID- 11769812 TI - Determination of low cadmium concentrations in wine by on-line preconcentration in a knotted reactor coupled to an inductively coupled plasma optical emission spectrometer with ultrasonic nebulization. AB - An on-line cadmium preconcentration and determination system implemented with inductively coupled plasma optical emission spectrometry (ICP-OES) associated to flow injection (FI) with ultrasonic nebulization system (USN) was studied. The cadmium was retained as the cadmium-2-(5-bromo-2-pyridylazo)-5 diethylaminophenol, Cd-(5-Br-PADAP), complex, at pH 9.5. The cadmium complex was removed from the knotted reactor (KR) with 3.0 mol/L nitric acid. A total enhancement factor of 216 was obtained with respect to ICP-OES using pneumatic nebulization (12 for USN and 18 for KR) with a preconcentration time of 60 s. The value of the detection limit for the preconcentration of 5 mL of sample solution was 5 ng/L. The precision for 10 replicate determinations at the 5 microg/L Cd level was 2.9% relative standard deviation (RSD), calculated from the peak heights obtained. The calibration graph using the preconcentration system for cadmium was linear with a correlation coefficient of 0.9998 at levels near the detection limits up to at least 1,000 microg/L. The method was successfully applied to the determination of cadmium in wine samples. PMID- 11769813 TI - Intercomparison study for the determination of selected polychlorinated biphenyls (PCBs) in feed matrices. AB - Analytical methodology currently employed for the determination of seven indicator PCBs in three compound feeds and fish meal has been evaluated in a collaborative study. The majority of the obtained relative standard deviations of the PCBs varied from 20 to 30%. On assuming a target relative standard deviation of 22% for the analytical results, statistical evaluation showed that about 80% of the participating laboratories delivered data within an acceptable range of +/ 44% of the assigned concentration in the test materials. However, between 10 and 20% of the participating laboratories reported unacceptable results. Major problems seemed to arise from insufficient separation of PCB congeners, low extraction efficiency, and calculation errors. Correct identification of the target PCB congeners was a prevalent problem if only one capillary column in combination with an electron capture detector (ECD) was employed. The correct preparation of the calibration solution by the laboratories turned out to be only a minor problem. The laboratories participating in this study employed quite different techniques at all stages of the analytical procedure. Principal component analysis indicated that laboratories using an internal standard tended to report higher values for the target analytes. If the PCB concentrations were related to the fat content of the sample, the variability of the reported results decreased for compound feed but increased for fish meal. These inconsistent results are probably due to the fact that fat is not an objective parameter but is defined by the analytical technique employed. It is assumed that harmonizing analytical methods for the determination of this parameter could improve the precision of the PCB results. PMID- 11769814 TI - Effects of tryptophan loading on verbal, spatial and affective working memory functions in healthy adults. AB - Serotonin (5-HT) appears to modulate affective behaviours by providing a homeostatic threshold around which other transmitters respond. This general principle of activity should hold for other types of behaviour, including cognition, but has not been extensively examined. We hypothesized, based on past findings, that increased 5-HT would constrain prefrontally guided working memory functions that are mediated by catecholamine neurotransmitters. Healthy adults ingested amino acid compounds designed to deplete and load systemic tryptophan levels in a repeated-measures crossover design. Outcome variables included total plasma tryptophan, serum prolactin levels and self-report measures of mood, as well as measures of motor skill, attention, memory span and working memory for verbal, spatial and affective stimuli. Our findings indicate decrements in working memory for verbal and affective stimuli following tryptophan loading versus depletion, as well as subtle changes in vigilant attention and motor coordination. Implications for the aetiology and treatment of affective disorders and psychosis are discussed. PMID- 11769815 TI - The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat. AB - The administration of a relatively high dose of antidepressant drugs produces an increased neuronal firing rate of the lateral septal nucleus (LSN) in the rat and a decreased immobility in rats forced to swim. However, it is unknown whether a minimally effective low-dose 21-day treatment with the selective serotonin reuptake inhibitor, fluoxetine, while reducing immobility in the forced swim test, also increases the neuronal firing rate of the LSN in Wistar rats. The total time of immobility decreased with a daily injection of 0.5, 1.0 or 2.0 mg/kg of fluoxetine (p < 0.001), and the lowest dose increasing the latency to the first immobility period (p < 0.0001) was 1.0 mg/kg. Therefore, the action of the 21-day fluoxetine treatment (1.0 mg/kg) on the firing rate of LSN neurones was tested in another group of rats. A total amount of 78 single-unit extracellular recordings was taken from the LSN of eight control rats (n = 40) and eight fluoxetine treated rats (n = 38). The LSN firing rate in the fluoxetine group was double (18.3 +/- 2.5 spikes per 10 s, p < 0.05) that in the control group (7.0 +/- 0.9 spikes per 10 s), and the first order interval of firing proved to be significantly lower in the fluoxetine group compared to the control group (384.3 +/- 22.3 and 639.7 +/- 27.5 ms, respectively; p < 0.05). In conclusion, the increased neuronal tiring rate of the LSN in the animals treated with a low dose of fluoxetine may be associated with an increased motivation to escape from the stressful situation that the forced swim represents. PMID- 11769816 TI - Effects of clonidine and diazepam on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. AB - Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30 500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). We examined the effects of two sedative/anxiolytic drugs, diazepam and clonidine, on prepulse inhibition of these two responses in healthy volunteers. Fifteen males (aged 18 35 years) participated in three sessions in which they received oral doses of placebo, diazepam 10 mg and clonidine 0.2 mg according to a balanced double-blind protocol. Thirty-minute simultaneous recordings of the electromyographic (EMG) responses of the orbicularis oculi muscle of the right eye and the vertex auditory evoked potentials took place 120 min after ingestion of clonidine and 60 min after ingestion of diazepam. Sound stimuli (1 kHz) were presented in 60 trials separated by variable intervals (mean 25 s): (i) 40-ms 115-dB ('pulse alone', 20 trials); (ii) 40-ms 85-dB (20 trials); (iii) 40-ms 85-dB, followed after 120 ms by 40-ms 115-dB ('prepulse/pulse', 20 trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. The amplitude of the EMG response was significantly reduced both by diazepam and by clonidine; neither drug significantly altered prepulse inhibition of the EMG response. Diazepam, but not clonidine, significantly reduced the amplitude of the N1/P2 potential; neither drug significantly affected prepulse inhibition of the N1/P2 potential. Both drugs reduced self-rated alertness and anxiety, and systolic blood pressure; clonidine, but not diazepam reduced diastolic blood pressure and salivation. The results confirm previous findings that sedative drugs can suppress the startle response without affecting prepulse inhibition of this response, and provide new information on the effects of these drugs on the N1/P2 potential and its inhibition by prepulses. PMID- 11769817 TI - Effects of haloperidol and clozapine on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. AB - Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30 500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we report the effects of the 'conventional' antipsychotic drug haloperidol and the 'atypical' antipsychotic clozapine on these responses. Fifteen males (aged 19-54 years) participated in four sessions at 7-day intervals, in which they received clozapine 3 mg, clozapine 6 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 3 h after treatment. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Clozapine 6 mg significantly reduced the amplitude of the EMG response without altering its inhibition by prepulses. Clozapine 6 mg did not affect the amplitude of the N1/P2 potential, but significantly attenuated prepulse inhibition of that response. Clozapine 3 mg and haloperidol had no significant effect on either response. Clozapine 3 mg and 6 mg, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Clozapine 6 mg reduced salivation. Haloperidol, but not clozapine, elevated serum prolactin levels. These results confirm that prepulse inhibition of the startle response and of the N1/P2 complex have different pharmacological sensitivities. The abililty of clozapine to attenuate the startle response may reflect its sedative action. The basis of the abililty of clozapine to suppress prepulse inhibition of the N1/P2 potential remains uncertain. PMID- 11769818 TI - Determining the optimal dose of haloperidol in first-episode psychosis. AB - Uncertainty exists as to the most appropriate dose of haloperidol in first episode psychosis. This study set out to determine whether ultra-low doses of haloperidol could successfully treat patients with first-episode psychosis. Thirty-five patients with a first episode of psychosis were treated with haloperidol in an open label, fixed protocol over a 12-week period with doses restricted to 1 mg per day for the first 4 weeks. Twenty-nine (83%) remained on haloperidol after 12 weeks at a mean dose of 1.78 mg per day, 16 (55%) had stabilized on 1 mg/day or less. The mean percentage reduction in Positive and Negative Symptom Scale score between baseline and 6 and 12 weeks was 30.3% (SD 20.9%) and 41.4% (SD 16.6%), respectively. There were no significant differences in mean extrapyramidal symptom ratings between baseline and 12 weeks. Ultra-low doses of haloperidol are effective and well tolerated in first-episode psychosis. Initial doses should be maintained for a sufficient period of time to allow for the medication to take full effect. PMID- 11769819 TI - Comparison between noradrenergic and serotonergic medications using the social adjustment scale: is drive enhancement necessary for recovery of social functioning? AB - The Social Adjustment Scale (SAS) was used to assess social functioning sequentially over 13 weeks in a group of 188 depressed outpatients randomized to either the noradrenergic antidepressant, nortriptyline, or the selective serotonin reuptake inhibitor, fluoxetine. Over the period of 13 weeks, there were no differences in total SAS scores between the nortriptyline and the fluoxetine group. In comparing the SAS subscale scores, which may measure different areas of motivation and behaviour (drive), there were differences between the two groups in only two subscales. At 13 weeks, the group randomized to fluoxetine were more impaired in marital role (p = 0.026) whereas, at 6 weeks, the group randomized to nortriptyline were more impaired in friction scores (p = 0.012). These results do not support the concept of specific augmentation of drive-related behaviour by noradrenergic medication. This challenges the earlier findings relating to drive enhancement and social adjustment using such medication. PMID- 11769820 TI - The pharmacovigilance of olanzapine: results of a post-marketing surveillance study on 8858 patients in England. AB - Olanzapine is an 'atypical' antipsychotic indicated for the treatment of schizophrenia. We analysed adverse events (AEs) reported in primary practice in England. Dispensed prescriptions issued between December 1996 and May 1998 provided exposure data. Questionnaires sent to general practitioners provided outcomes. Frequently reported AEs were: drowsiness/sedation (n = 19), extrapyramidal disorder (n = 13) and unspecified side-effects (n = 33). Events with highest incidence density in first month and reason for stopping were: drowsiness/sedation [n = 153, incidence density (ID)1 18.9], weight gain (n = 117, ID1 8.9) and malaise/lassitude (n = 65, ID1 5.2). Extrapyramidal disorders were more common in elderly population (> 70 years, ID1 3.6, risk 26.0 per 1,000 patients) compared to < 70 years (ID1 1.1, risk 8.4 per 1,000 patients). Serious suspected adverse reactions were neuroleptic malignant syndrome (n = 1) and angioneurotic ooedema (n = 2). There were eight reports of diabetes mellitus assessed as possibly due to olanzapine. Diabetes mellitus was an unlabelled AE and possible signal generated by prescription-event monitoring. PMID- 11769821 TI - Ecstasy use: cognitive deficits related to dosage rather than self-reported problematic use of the drug. AB - Previous research has shown drug-free Ecstasy users to demonstrate selective cognitive impairment. However, there seems to be a degree of individual variation in the occurrence of such deficits. The present study aimed to assess whether these cognitive deficits are related to an awareness of problematic Ecstasy use, or to past drug dosage. Twenty regular Ecstasy users who reported experiencing Ecstasy-related problems were compared with 20 Ecstasy users who had not reported any previous problems. The two groups displayed similar past histories in relation to a range of illicit drugs, and were divided into low, medium and high users. The controls comprised 20 illicit recreational drug users who had never taken Ecstasy. Executive task measures comprised the Tower of London (TOL), the Wisconsin Card Sorting Task (WCST) and spatial working memory. Immediate and delayed word recall, matched verbal recognition and recall and simple reaction time were also included. Both Ecstasy groups performed significantly worse than controls on two executive measures: TOL planning time and spatial working memory score. There were no differences in cognitive impairment between the Ecstasy users who complained of problems and those who did not. In both groups, decrement on executive tasks was demonstrated as a function of previous drug dose. The study confirms that heavy Ecstasy polydrug use may culminate in selective executive deficits. It also demonstrates that two differently self-perceived Ecstasy groups showed similar cognitive impairment, despite only one group complaining of problems. Because all Ecstasy participants also consumed a range of other illicit drugs, the results are reflective of Ecstasy polydrug use in individuals who use Ecstasy as a drug of preference. PMID- 11769822 TI - Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findings. AB - Anxiety disorders are associated with low vagal control of heart rate and increased risk of cardiac mortality and sudden cardiac death. This study examined whether the herbal anxiolytic, kava, produces improvement in vagal control in generalized anxiety disorder. Before and after treatment with placebo (n = 7) or kava (n = 6), two indices of vagal control were measured under supine conditions using power spectral analysis: baroreflex control of heart rate (BRC) and respiratory sinus arrhythmia (RSA). Significantly more patients treated with kava showed improved BRC compared to the placebo group (p < 0.05). Furthermore, the magnitude of improvement in BRC was significantly correlated with the degree of clinical improvement (p < 0.05). RSA did not respond to treatment. These preliminary findings suggest that kava might exert a favourable effect on reflex vagal control of heart rate in generalized anxiety disorder patients. The parallel clinical and BRC responses may reflect an underlying common effect of this herbal anxiolytic. PMID- 11769823 TI - Reversed effects of RU486 and anisomycin on memory retention of light exposure or corticosterone facilitation in the dark-incubated chicks. AB - Memory formation for a weak passive avoidance task in the dark-incubated chicks is facilitated by light exposure or corticosterone administration at optimally pre-hatch time points. To explore the potential mechanisms underlying activation of brain memory function development by light or corticosterone exposure during late embryo, steroid receptor antagonist RU486, or protein synthetic inhibitor anisomycin, was administered intraembryonically to the embryos of either only 24 h light-exposure or complete dark-hatched on embryonic day 20 (E20). The results showed that RU486 and anisomycin significantly retarded the facilitated retention both by light and corticosterone exposure in the dark-incubated chicks. They also suggest that the act of corticosterone or light exposure on the development of brain memory function is mediated by the effect of steroid receptor, or afterward on related protein syntheses that is involved in memory formation of post-hatched performance of day-old chicks. PMID- 11769824 TI - Antipsychotic induced hyperprolactinaemia: a series of illustrative case reports. AB - Hyperprolactinaemia is a common side-effect of many antipsychotic drugs but, in comparison to extrapyramidal side-effects, it has received little attention. Four case reports are presented which illustrate important clinical and pharmacological aspects of the syndrome. Two of the cases were caused by conventional antipsychotic drugs and two by risperidone, an atypical antipsychotic. Symptoms included gynaecomastia, galactorrhoea, amenorrhoea and sexual dysfunction. Three patients were switched to a prolactin sparing antipsychotic leading to normalization of serum prolactin and resolution of the symptoms. Patients prescribed prolactin elevating antipsychotics should, where possible, have this issue explained to them prior to commencing treatment and be screened for symptoms suggestive of hyperprolactinaemia before starting treatment and regularly thereafter. PMID- 11769825 TI - Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. AB - The glutamate hyperfunction hypothesis of schizophrenia has been proposed largely on the basis of studies in post-mortem brain and the lack of efficacy of glutamate agonists as antipsychotic drugs. Recent reports have also suggested that the addition of lamotrigine, a glutamate excess release inhibitor, can cause a dramatic improvement in clozapine treatment-resistant patients, as well as attenuate the neuropsychiatric effects of ketamine in healthy volunteers. To explore the glutamate hyperfunction hypothesis, patients with schizophrenia who were treatment-resistant to current antipsychotic medications were augmented with either lamotrigine (n = 17) or topiramate (a glutamate kainate/alpha-amino-3 hydroxy-5-methyl-4-isoxazolaproprionate antagonist that potentiates GABA function) (n = 9) for 24 weeks. Patients receiving lamotrigine augmentation of clozapine had a significant decrease in Brief Psychiatric Rating Scale score after 2 weeks of treatment. There was no significant improvement when lamotrigine was added to risperidone, haloperidol, olanzapine or fluphenthixol. There was also no significant improvement observed with topiramate augmentation of clozapine, olanzapine, haloperidol and fluphenthixol. These preliminary data support previous evidence that lamotrigine is an effective augmentation agent for clozapine. Although limited by sample size, the findings also suggest glutamate hyperfunction in schizophrenia may have a presynaptic basis and that atypicals with low dopamine receptor occupancy may have antagonistic actions on glutamate function which confer additional antipsychotic activity. PMID- 11769826 TI - Lethal catatonia responding to high-dose olanzapine therapy. AB - We present the case of a 31-year-old woman with recent refractory bipolar disorder who developed a malignant syndrome preceded by catatonic motor features. This resistant case of lethal catatonia responded selectively to high-dose olanzapine treatment. The case illustrates the need to consider lethal catatonia in apparent cases of neuroleptic malignant syndrome that do not respond to conventional treatment with dantrolene and bromocriptine. PMID- 11769827 TI - The diminishing implant gap. PMID- 11769828 TI - Quality assessment of randomized controlled trials of oral implants. AB - The aim of this study was to assess the quality of randomized controlled trials (RCTs) concerned with the effectiveness of oral implants and to create a trial register. A multilayered search strategy was used to identify all RCTs published by the end of 1999 in any language. The Cochrane Oral Health Group specialist register, PubMed, and personal libraries were searched. Seventy-four RCTs were identified. Forty-three articles, not presenting the same patient material, were independently assessed by 3 researchers using a specially designed form. A statistician assessed all trials for the appropriateness of statistics. The quality of each study was assessed on 7 items, including 3 key domains. Randomization and concealment allocation procedures were not described in 30 articles (70%). Reasons for withdrawals were not given in 10 reports (23%). No attempt at blinding was reported in 31 studies (72%). The quality of RCTs of oral implants is generally poor and needs to be improved. PMID- 11769829 TI - Retentiveness of dental cements used with metallic implant components. AB - There is limited dental literature evaluating the retentive capabilities of luting agents when used between metal components, such as cast metal restorations cemented onto machined metal implant abutments. This study compared the retentive strengths of 5 different classes of luting agents used to cement cast noble metal alloy crowns to 8-degree machined titanium cementable implant abutments from the Straumann ITI Implant System. Sixty prefabricated 5.5-mm solid titanium implant abutments and implants were used; 30 received the standard surface preparation and the other 30 received an anodized surface preparation. Anodized implant components were used to reflect current implant marketing. Sixty castings were fabricated and randomly paired with an abutment and implant. A total of 12 castings were cemented onto the implant-abutment assemblies for each of the 5 different luting agents (zinc phosphate, resin composite, glass ionomer, resin reinforced glass ionomer, and zinc oxide-non-eugenol). After cementation, the assemblies were stored in a humidor at room temperature prior to thermocycling for 24 hours. Each casting was pulled from its respective abutment, and the force at which bond failure occurred was recorded as retentive strength. A statistically significant difference was found between the 5 cements at P < or = .001. Of the cements used, resin composite demonstrated the highest mean retentive strength. Zinc phosphate and resin-reinforced glass-ionomer cements were the next most retentive, while glass ionomer and zinc oxide-non-eugenol cements demonstrated minimal retention. In addition, retention was not altered by the use of an anodized abutment surface. PMID- 11769830 TI - Rabbit bone marrow response to bovine osteoinductive proteins and anorganic bovine bone. AB - The effects caused by the implantation of bioabsorbable hydroxyapatite (HA) bound to a pool of bone morphogenetic proteins (BMPs) and other bone noncollagenous hydrophobic proteins mixed with anorganic bovine bone inside rabbit bone marrow were assessed. Within the interior of hollow cylindric titanium prototypes, the following biomaterials were inserted: (1) test group: HA containing a pool of BMPs and noncollagenous hydrophobic proteins mixed with anorganic bovine bone; (2) control group: HA without any protein mixed with anorganic bovine bone; and (3) negative control group: blood clot. The cylinders were placed surgically into the medial portion of the tibiae of 7 rabbits in a manner that allowed the biomaterials to contact just the bone marrow. Morphometric analysis showed that: (1) the biomaterials containing the protein mixture resulted in significantly less new bone than the biomaterials without such a mixture; (2) the group without the protein pool formed larger amounts of bone within the cylinder when compared to the negative control (blood clot only); and (3) the biomaterials containing the protein pool did not show any difference in relation to the negative control. It was concluded that a pool of BMPs and other bone noncollagenous hydrophobic proteins had an inhibitory effect on osteogenesis, and that the biomaterials without a protein pool formed a favorable substrate to bone formation. PMID- 11769831 TI - Effects of ion beam-assisted deposition of hydroxyapatite on the osseointegration of endosseous implants in rabbit tibiae. AB - The aim of this study was to evaluate the effects of coating implants with hydroxyapatite (HA) by an ion beam-assisted deposition (IBAD) method and to compare them with implants prepared with sand-blasted and machined surfaces. Examination of osteoblast cultures displayed no difference in the secretion of alkaline phosphatase (ALP) between the various surfaces, but the IBAD-HA specimen showed low ALP secretion (P < .05). Removal torque tests showed that implants coated with HA by the IBAD method had values similar to the implants with a sandblasted surface, but values for the machined-surface implants differed. Implants placed in a group of ovariectomized rabbits showed lower mechanical test values than implants placed in sham-operated rabbits (P < .05). Implants coated with HA by the IBAD method demonstrated the highest mean bone-to-metal contact ratio on all threads and on the 3 best consecutive threads, followed by the implants with a sandblasted surface and implants with a machined surface (P < .05). Hydroxyapatite-coated implants showed a slightly higher bone-to-implant contact ratio than sandblasted implants, but no statistically significant difference was seen between the 2 materials. The implants placed in ovariectomized rabbits showed lower amounts of bone-to-metal contact than the implants placed in sham-operated rabbits, but no statistically significant difference was seen between the 2 groups. Evaluation of bone volume on all threads and the 3 best consecutive threads showed no statistically significant difference among the different surface treatment groups, but lower bone volume was seen in the ovariectomized rabbits than in the sham-operated animals (P < .05). PMID- 11769832 TI - Effects of mechanical and thermal fatigue on dental drill performance. AB - Osseous integration of dental implants depends on the use of proper surgical technique during site preparation, including the prevention of thermal injury to the surrounding bone. Heat generation during drilling has been reported to positively correlate with the production of forces at the surgical site. In this study, peak torque and axial load levels were measured during a drilling procedure into a polymeric material simulating the human mandible. Axial rotary milling was performed using 5 different twist drill designs (3i Irrigated Tri Spade, 3i Disposable, Nobel-Biocare, Straumann, and Lifecore) of 15 to 20 mm in length and 2 to 2.3 mm in diameter, at a free-running rotational speed of 1,500 rpm and continuous feed rate of 3.5 mm/second, to a total depth of 10.5 mm. Ten drills representing each of the 5 types (n = 50) were subjected to 30 individual drill "pecks" and heat-sterilized every 3 "pecks" to determine the effects of cyclic mechanical and thermal loading on drill performance. Normal stress (sigma) and shear stress (tau) were calculated from the kinetic data and drill geometries. A drill efficiency coefficient (mu) was also calculated as the ratio of torsional resistance to translational resistance. Overall, the hypotheses of drill performance dependency on drill type as well as mechanical and thermal accumulated loading were tested and confirmed (P < .05). The 5 drill types produced a range of normal stresses (2.54 to 5.00 MPa), shear stresses (9.69 to 29.71 MPa), and efficiency (1.16 to 3.16) during repeated testing. Scanning electron microscopic images revealed minor deformations in the cutting edges of the tri-spade drills following testing. PMID- 11769833 TI - An investigation of 131 consecutively placed wide screw-vent implants. AB - Between February 1995 and May 1996, 71 patients received treatment that involved 1 or more wide Screw-Vent implants. A total of 131 wide implants were placed. All patients were recalled 1 year after loading. Seven patients (14 implants) were lost to follow-up. Six implants were removed before completion of prosthetic treatment. One hundred eleven implants were evaluated at the recall examination. Almost all implants (109) supported a fixed prosthesis; in the majority of patients (93 implants), it was a fixed partial prosthesis. The mean loading time was 17 months (range, 11 to 21 months). No implants were lost during the loading period. The overall survival rate was 95%. The survival rate for mandibular implants was 94%; for maxillary implants, it was 96%. These percentages were not statistically different. Crestal bone remodeling was examined using periapical radiographs. After 17 months in function, only 3 implants (2.5%) presented bone loss beyond the first thread. PMID- 11769834 TI - Evaluation of maxillary sinus membrane response following elevation with the crestal osteotome technique in human cadavers. AB - Implant placement in the posterior maxilla often requires elevation of the sinus floor, which can be achieved through either the modified Caldwell-Luc or the crestal osteotome technique. The objectives of this study were to evaluate (a) the resistance to perforation of maxillary sinus membranes obtained from formaldehyde-fixed cadavers in vitro, (b) the frequency and extent of membrane perforations occurring after sinus floor elevation in cadavers using the crestal approach, and (c) the amount of membrane elevation (doming) that can be achieved using the crestal approach. Pretreatment of maxillary sinus membrane tissues with commonly used tissue softeners did not have a statistically significant effect on resistance to perforation. Maxillary sinus membranes were elevated 4 to 8 mm in formaldehyde-fixed cadavers using the osteotome technique; implants were placed. Of the 25 sites that received implants, only 6 showed perforations, as assessed by double-blind investigation after dissection of the lateral wall of the nose, allowing direct examination of the sinus cavity. Perforations were categorized as Class I (< or = 2 mm with exposure of the implant into the sinus cavity and loss of doming); Class II perforations (> or = 2 mm) were associated with proximity of the osteotomy site to the medial wall of the sinus or the presence of septae. These results indicated that the crestal osteotome approach compared favorably to the modified Caldwell-Luc technique as it relates to the frequency of maxillary sinus membrane perforations and the degree of achievable membrane elevation. PMID- 11769835 TI - Enhancing osseointegration by capacitively coupled electric field: a pilot study on early occlusal loading in the dog mandible. AB - Expeditious postoperative appositional growth of bone to dental implants is desired for clinically successful fixation of oral implants. The present study was performed to evaluate the effect of applying a capacitively coupled electric field (CCEF) followed by functional loading on peri-implant osteogenesis in the dog mandible. Nine adult beagles were used in this study. All premolars on both sides of the mandible were removed from each dog. A physio-odontlam implant (POI, Ti-6AI-4v) with 2 stages (3.7 mm in diameter and 8.0 mm in length), whose surface had been treated with anodic oxidation and sandblasted, was placed into each test site by self-tapping. Daily application of CCEF (8 hours per day) was initiated on the day following surgery and continued for 14 days or 21 days. After CCEF treatment was finished for each period, a prosthetic abutment and a straight post were placed on each implant. Four days after placement of the post, implants were placed under functional loading for 30 days. The dogs were then sacrificed, and histologic and radiographic studies of the mandible were performed. Relatively well calcified, mature bone with a lamellar-like structure was observed by contact microradiography and histologic study (double staining with basic fuchsin methylene blue) of the peri-implant region on the CCEF-treated samples. In contrast, poorly calcified, immature bone without a lamellar structure was observed in control sites not treated with CCEF. The bone area ratios of the CCEF treated sides were larger than those of control sides. These results suggest that the application of CCEF after implant placement may enhance peri-implant osteogenesis, even with functional loading. PMID- 11769836 TI - Periosteoplasty for soft tissue closure and augmentation in preprosthetic surgery: a surgical report. AB - Soft tissue closure is a critical factor in preprosthetic surgery and implant placement. In large transverse or vertical bone augmentations, there is often insufficient or very thin mucosa available. Soft tissue dehiscences and bone or implant exposure may result. Based on the application of a periosteal flap, the presented method solves this problem. The flap is prepared in the neighboring area and folded into the corresponding surgical area. It not only provides good soft tissue coverage but also results in soft tissue augmentation. Periosteoplasty has been successfully applied in over 60 patients over the last 2 years. PMID- 11769837 TI - Clinical evaluation of a bilayered collagen membrane (Bio-Gide) supported by autografts in the treatment of bone defects around implants. AB - The aim of this study was to determine the efficacy of a bioresorbable collagen membrane (Bio-Gide) in combination with autogenous bone grafts in the treatment of peri-implant dehiscences, fenestrations, or limited vertical defects. Eighteen titanium dental implants with exposed threads placed in 17 patients were studied. Autogenous bone was used in all cases to fill the defect and maintain the space underneath the barrier. The collagen membrane was trimmed and adapted to cover the defect in a saddle configuration. The membrane absorbed the blood and easily covered and adhered to the underlying bone. It was not stabilized by any retentive means. Sixteen to 32 months postoperatively, the sites were reentered and the amount of bone regenerated was measured. The results showed significant bone gain (average 87.6%) in the treatment of peri-implant defects with Bio-Gide and autogenous bone. PMID- 11769838 TI - Growth analysis of a patient with ectodermal dysplasia treated with endosseous implants: a case report. AB - Congenital absence of multiple teeth and poorly developed alveolar ridges are associated with ectodermal dysplasia. Affected patients often require dental prosthetic treatment during their developmental years. Maxillofacial growth and development in a preadolescent female patient with ectodermal dysplasia following oral rehabilitation with maxillary and mandibular endosseous dental implants is reported. Four maxillary and 4 mandibular implants were successfully integrated and restored at 8 years of age. Growth analysis 12 years later revealed that the implants followed maxillary and mandibular growth displacement. Minor impaction of the maxillary implants was observed, and mandibular implants were affected by the mandibular growth rotation, which led to a change in implant inclination. The treatment outcome is compared to similar previously reported studies and cases. PMID- 11769839 TI - Managing soft tissue fenestrations in bone grafting surgery with an acellular dermal matrix: a case report. AB - The success of bone grafting procedures depends largely on the management and integrity of the gingival flaps. Soft tissues aid in the protection of the bone graft, participate in the revascularization of the newly formed hard tissues, and play an important role in the esthetic outcome of the reconstructive phase. Acellular dermal matrix (ADM) is a material obtained from human skin and used in plastic and reconstructive surgery as an allograft. It acts as a bioactive substrate for cell attachment and proliferation. The outcome of the use of ADM as a dressing material to treat flap fenestrations in bone grafting surgery is presented. PMID- 11769840 TI - Utilization of a plastic "washer" to prevent auricular prosthesis abutment overgrowth: report of a case and description of a technique. AB - Skin overgrowth of auricular implant abutments can be a difficult and frustrating problem, leading to multiple procedures and delaying the placement of a definitive prosthesis. In the present patient, plastic rings or "washers" were employed to successfully deal with this problem. A discussion of the management of peri-implant soft tissues is presented. PMID- 11769841 TI - Potential applications of the erbium:YAG laser in endourology. AB - The holmium:YAG laser has become the laser of choice in endourology because of its multiple applications in the fragmentation of kidney stones, incision of strictures, and coagulation of tumors. This paper describes the potential use of a new laser, the erbium:YAG laser, for applications in endourology. Recent studies suggest that the Er:YAG laser may be superior to the Ho:YAG laser for precise ablation of strictures with minimal peripheral thermal damage and for more efficient laser lithotripsy. The Er:YAG laser cuts urethral and ureteral tissues more precisely than does the Ho:YAG laser, leaving a residual peripheral thermal damage zone of 30 +/- 10 microm compared with 290 +/- 30 microm for the Ho:YAG laser. This result may be important in the treatment of strictures, where residual thermal damage may induce scarring and result in stricture recurrence. The Er:YAG laser may represent an alternative to the cold knife and Ho:YAG laser in applications where minimal mechanical and thermal insult to tissue is required. PMID- 11769842 TI - Hand-assisted laparoscopic approach to multiple-organ removal. AB - BACKGROUND: Over the past decade, laparoscopy has matured to a common, and in some cases, standard surgical approach. Over this time period, many technological advances have contributed to this progression, one of which is hand assistance. Hand-assisted laparoscopy allows a shortened technical learning curve, security and ease in dissection, the ability to remove organs en bloc, and shorter operative times while maintaining the postoperative advantages of laparoscopy. PATIENTS AND METHODS: We present our experience with a hand-assisted laparoscopic approach for two patients requiring bilateral nephrectomy in preparation for renal transplantation and a third patient having concurrent right simple nephrectomy and simple cystectomy for chronic pyocystis. RESULTS: The hand assisted approach allowed for utilization of one anesthetic, repositioning of the patient without violating the sterile field, and a short convalescent time. The average hospital stay was 5 days, including two patients who required postoperative revascularization of their clotted arteriovenous fistulas. CONCLUSION: The established indications for hand-assisted laparoscopy include removal of large surgical specimens en bloc, anticipated difficult dissection, and failure of standard laparoscopic procedure progression. We propose that removal of multiple organs should be added to this list. PMID- 11769843 TI - Hand-assisted vs. retroperitoneal laparoscopic nephrectomy. AB - PURPOSE: We retrospectively compared our initial experience with the hand assisted and retroperitoneal laparoscopic nephrectomy techniques to determine if there are important differences between these approaches. PATIENTS AND METHODS: Twenty-four laparoscopic cases consisting of 12 hand-assisted and 12 retroperitoneal nephrectomies were compared. All cases but one were radical nephrectomies with intact specimen extraction performed for suspected stage T1 neoplasms. Data were collected from medical records and a postoperative questionnaire. To determine if significant learning curves existed, the first six nephrectomies in each group were compared with the second six nephrectomies on the basis of operative criteria. The two groups did not differ significantly in age, body mass index, ASA rating, or number of previous abdominal operations. RESULTS: Although the mean tumor volume was greater in the hand-assisted group than the retroperitoneal group, the difference did not quite reach statistical significance (91.19 v 24.7 cc3; P = 0.06). The mean operative time, estimated blood loss, narcotic use (milligrams of intravenous morphine equivalent), hours to oral intake, hospital stay, and estimated percent activity at 2 weeks for the hand-assisted group (238.33 min, 293.75 mL, 35.7 mg, 17.56 hours, 4.4 days, 74.75%, respectively) were not significantly different from the values in the retroperitoneal group (255.83 min, 141.67 mL, 24.5 mg, 22.36 hours, 3.6 days, 76.91%). We found no significant difference in the mean operative times for the first and second six cases in either group. CONCLUSION: In the initial experience and comparison of hand-assisted and retroperitoneal laparoscopic nephrectomy, we found no significant differences in operative time, estimated blood loss, narcotic usage, hours to oral intake, hospital stay, or activity level at 2 weeks postoperatively. A randomized trial is under way at our institution. PMID- 11769844 TI - Minimally invasive extraperitoneal lymphadenectomy: clinical validation of an original technique. AB - PURPOSE: To validate an original technique described for pelvic node dissection. PATIENTS AND METHODS: A series of 192 patients were included in this study. The surgical technique we reported in 1987 is based on the use of a special retractor called the pelvioscope. The incision is the classical MacBurney incision on the right and its equivalent on the left. After the division of the muscles, the peritoneum is mobilized medially, and the pelvioscope is introduced. The node resection is then performed with classical surgical instruments. RESULTS: In total; 151 bilateral, 20 unilateral right, and 21 unilateral left node dissections have been performed. In one case, dissection was not possible on both sides, and in two cases, the dissection was not complete on one side (patients previously operated on). The average intraoperative time was 69 minutes for a unilateral procedure and 103 minutes for a bilateral procedure. The mean number of pelvic lymph nodes removed was 5.6 on each side. The overall rate of complications was 7.3%. CONCLUSION: The effectiveness of this minimally invasive surgery is clear, and the morbidity is low. PMID- 11769845 TI - The broken stone basket: configuration and technique for removal. AB - PURPOSE: We investigated the ease of breakage of endoscopic stone baskets with the holmium:yttrium-aluminum-garnet (YAG) laser and their resultant configuration. More importantly, possible safe methods of retrieval were evaluated. MATERIALS AND METHODS: Endoscopic stone baskets from Bard (Platinum Class 2.4F Flat and 3.0F Helical Wire), Cook (3.2F Captura, 3.2F Atlas, 3.0F N Circle, 4.5F N-Force), and Microvasive (2.4F Zero Tip, 3.0F Gemini, 3.0F Segura) were broken once using the holmium:YAG laser. The energy (kJ) required to break one of the wires was recorded. Configuration was documented using photographs. Baskets were disassembled and assessed for extraction through a 7F open-ended catheter, an 8F/10F set, and a 20F peel-away sheath. RESULTS: Tipless baskets (N Circle, Zero Tip) broke the easiest (range 0.02-0.03 kJ). Tipped baskets (Segura, Platinum Class Flat and Helical, Gemini, Captura, N-Force, Atlas) were more resistant, but all broke within the range (0.06-0.78 kJ) typically used for intracorporeal lithotripsy. Broken segments of wire tended to protrude outward, with tipless baskets having less change in configuration than tipped baskets. Tipless baskets could easily be pulled into any of the extracting devices, whereas tipped baskets could not. CONCLUSIONS: Baskets break at typical holmium:YAG intracorporeal lithotripsy energy settings. Tipless baskets break easiest and assume a safer configuration. Tipless baskets are extracted easily through a 7F open-ended catheter, 8F/10F set, or 20F sheath, while tipped baskets are unable to be extracted through any of these. PMID- 11769846 TI - Gas-containing renal stones treated with percutaneous nephrolithotomy: case report. AB - We present a rare case of E. coli emphysematous pyelonephritis with sepsis. The radiologic presentation consisted of multiple radiolucent gas-filled, free floating uric acid calculi in a hydronephrotic renal pelvis. The infection was treated by intravenous fluids and antibiotics and percutaneous nephrostomy drainage. The patient was rendered stone free by percutaneous nephrolithotomy and ultrasound lithotripsy. PMID- 11769847 TI - One shot: a novel method to dilate the nephrostomy access for percutaneous lithotripsy. AB - BACKGROUND AND PURPOSE: The creation of the nephrostomy access is a fundamental step of percutaneous nephrolithotripsy (PCNL). Dilation of the track is usually achieved with multiple incremental flexible exchange dilators of the Amplatz type, metal telescoping dilators of the Alken type, or a balloon. Currently, balloon dilation is regarded as the most modern and safest system, though it has the disadvantage of relatively high cost. The aim of this study was to demonstrate that a procedure that we named "one shot," which consists of a single dilation of the track with a 25F or 30F Amplatz dilator, compares favorably in terms of efficacy, costs, and length with the other techniques of track dilation, without a significant increase in morbidity. PATIENTS AND METHODS: Seventy-eight consecutive patients who underwent PCNL for stone disease from June 1998 to July 1999 were considered and divided into three groups according to the type of tract dilation used: A (Alken telescoping dilators), B (balloon), or C (one shot). Radiologic exposure, blood loss, and costs were evaluated. RESULTS: The one-shot procedure compared favorably with both of the other dilation techniques without an increase in morbidity and with significant reductions in X-ray exposure and costs. Indeed, significant differences in estimated blood loss were observed between groups B and C and the minor bleeding for group C. CONCLUSION: Our experience indicates that one-shot dilation is feasible in the majority of patients. It is as safe and effective as the technique regarded today as the gold standard but less time consuming and less expensive. These encouraging results should be confirmed by further studies. PMID- 11769848 TI - Efficiency and efficacy of different intracorporeal ultrasonic lithotripsy units on a synthetic stone model. AB - PURPOSE: The efficiency and efficacy of the available intracorporeal ultrasonic lithotripters were compared in a stone model experiment. MATERIALS AND METHODS: Plaster of Paris (POP) stone phantoms having ratios of 1:1, 1.5:1, and 2:1 with water were fabricated into cubes of various hardnesses weighing an average of 24.6 g. The stones were immersed in water in a plastic container, and continuous irrigation through a rigid nephroscope was used. Ultrasonic lithotripters from ACMI, Olympus, Storz, and Wolf manufacturers were evaluated for efficacy in breaking up the three POP concentrations. Time to complete stone fragmentation, occurrence of probe or tubing occlusion, and probe overheating were evaluated. RESULTS: Efficiency of fragmentation and time to fragmentation of the Storz lithotripter were significantly different from those of the Wolf (p = 0.01 and p = 0.02, respectively) and ACMI (p = 0.001 and p = 0.02, respectively) lithotripters. Comparison of the efficiency of fragmentation and time to fragmentation of the ACMI and Wolf lithotripters showed significant differences (p = 0.005 and p = 0.03, respectively) in favor of the Wolf device. The Olympus lithotriptor resulted in incomplete fragmentation of phantoms of all POP concentrations. CONCLUSION: The Storz ultrasonic lithotriptor was found to have the lowest fragmentation time and highest efficiency in the fragmentation of phantom stones. PMID- 11769849 TI - Endoscopic lithotripsy with a new device combining ultrasound and lithoclast. AB - BACKGROUND AND PURPOSE: Endoscopic lithotripsy is still the method of choice for a number of stones, especially large stones. Various disintegration techniques exist. We investigated the combination of two of these techniques: ultrasound and pneumatic lithotripsy. PATIENTS AND METHODS: Fourteen consecutive patients with renal and one patient with bladder stones were treated with this new device. Ultrasound and pneumatic lithotripsy could be used independently or simultaneously. RESULTS: Disintegration and stone removal was fast. The use of forceps or other instruments could generally be avoided. No complications attributable to the lithotripsy device were observed. CONCLUSION: The combined ultrasound/pneumatic lithotripsy device is safe and highly effective. It reduces treatment time and enhances surgeon's comfort. PMID- 11769850 TI - Assessment of optimal balloon size for rupture of the ureteropelvic junction and mid-ureter in a porcine model. AB - PURPOSE: Balloon dilation potentially represents a safer and simpler technique for the treatment of ureteropelvic junction (UPJ) obstruction and ureteral strictures. Using a porcine model, we sought to establish the optimal balloon size for endoballoon rupture of the UPJ and ureter. MATERIALS AND METHODS: The efficacy of endoballoon rupture of the proximal and middle ureter with 24F, 30F, and 36F balloon catheters was compared in 19 female minipigs. At the proximal ureter, the effect of the rate of dilation also was evaluated for each balloon size. Extravasation of methylene blue-stained contrast material was assessed with retrograde pyelograms and direct laparoscopic vision. After acute sacrifice, the dilated segments were evaluated histologically with hematoxylin and eosin and Masson's trichrome staining. RESULTS: At the proximal ureter, free extravasation of contrast was observed in 61% of the rapid inflation and 72% of the slow inflation trials; contained extravasation was noted in 28% of the rapid inflation and 17% of the slow inflation trials. Except for two of the 24F slow inflation trials, all of the proximal ureteral trials produced at least one full-thickness tear into the periureteral fat. Grossly, the tears appeared linear with various lengths and no consistent orientation. Rapid inflation and increasing balloon size tended to produce a ureterotomy with less damage to the ureter surrounding the tear. At the mid-ureter, none of the balloon sizes consistently produced a transmural tear. CONCLUSIONS: Rapid dilation and use of a 36F balloon capable of maintaining a low profile after inflation may result in a cleaner proximal ureterotomy with less distortion of the untorn neighboring proximal ureter. Both 36F and 30F balloons consistently produced a full-thickness proximal ureterotomy in normal porcine tissue. For mid-ureteral strictures, balloon dilation to even 36F may fail to create a suitable ureterotomy. However, it must be noted that dysplastic or scarred tissue may respond differently to dilation than the more elastic normal porcine tissues used in this study. PMID- 11769851 TI - Making hand-assisted laparoscopy easier: preventing CO2 leak. AB - Hand assistance has been a significant advance in making laparoscopy an easier and safer method for certain procedures such as nephrectomy. The value of this technique is realized when comparing patient outcomes (e.g., less postoperative pain, shorter hospital stay, quicker recovery time) with those of the standard open approaches. One reported disadvantage of the Pneumo Sleeve device for hand assisted laparoscopy is leakage of CO2 gas from around the ring base. We describe in detail our technique to secure the Pneumo Sleeve to the abdomen in such a way as to prevent leakage of intraperitoneal gas and fluid. PMID- 11769853 TI - Endoscopic extraction of an ejaculatory duct calculus to treat obstructive azoospermia. AB - Calculous obstruction of an ejaculatory duct is an uncommon cause of azoospermia or low-volume oligospermia in the infertile man. We report the case of a 32-year old man with azoospermia, low ejaculate volume, and transrectal ultrosonography (TRUS) findings of bilateral seminal vesicle distention. On cystoscopy for planned transurethral resection of the ejaculatory ducts, a calculus obstructing the right ejaculatory duct at the verumontanum was discovered and removed. Three months later, semen analysis showed improvements in volume, sperm concentration, and sperm motility. An ejaculatory duct calculus should be included in the differential diagnosis of obstructive azoospermia or low-volume oligospermia. Magnetic resonance imaging or TRUS may be advisable to identify ductal calculi. PMID- 11769852 TI - Removal of urolume endoprosthesis using holmium:YAG laser. AB - A potential complication of UroLume endoprosthesis is migration, which may necessitate removal of the stent. Stent removal may be associated with complications such as urethral injury, bleeding, and external sphincter trauma. We report a patient in whom a holmium:yttrium-aluminium-garnet (Ho:YAG) laser was used to cut the UroLume endoprosthesis into fragments, which led to easy and uneventful stent removal. PMID- 11769854 TI - Electrovaporization using a rollerball electrode for flat or small papillary tumors of the bladder: basic study in dogs. AB - PURPOSE: We investigated electrovaporization of flat bladder tumors with a rollerball electrode 3 mm in diameter as a substitute for conventional transurethral resection with a cutting loop. MATERIALS AND METHODS: A basic study of the action of electrovaporization was performed in dogs. The bladder was exposed under general anesthesia in three mongrel dogs. The rollerball electrode was attached to the resectoscope and inserted into the bladder via a cystostomy. Then electrovaporization was performed with a low or high pressure on the electrode tip and a speed of about 1 cm/sec using a Force 40 generator. The cutting mode power was set at 100 W or 200 W. The effects of the rollerball and cutting loop electrodes were also examined in the coagulation mode (45 W) as a control. RESULTS: A deeper vaporization zone was obtained by using a power of 200 W in the cutting mode than with a power of 100 W, and a desiccation zone was found below the vaporization zone (VZ). The VZ was thicker with a high contact pressure than with a low contact pressure. This VZ was deeper than the tissue defect and heat-affected zone obtained using a rollerball electrode or cutting loop electrode in the 45 W coagulation mode. CONCLUSION: Although caution is required because the VZ can become too deep with excessive pressure, the rollerball electrode seems to be safer and more useful than the cutting loop electrode for resection of flat or small papillary bladder tumors. PMID- 11769855 TI - Why American women are not receiving state-of-the-art gynecologic cancer care. AB - American women are not receiving state-of-the-art gynecologic cancer care. The three most common gynecologic cancers-endometrial, ovarian, and cervical-are quite uncommon in the United States when compared with othermalignancies. Nevertheless, their importance is clearly out of proportion to their incidence since the annual death rate from ovarian cancer alone is about one third that of breast cancer. And cervical cancer is a very common malignancy of women worldwide. The major problem accounting for suboptimal treatment of ovarian and endometrial cancers in the United States is incomplete surgical staging performed by nongynecologic oncologists. In the case of cervical cancer treatment, suboptimal care is attributable to specialty territoriality and the lack of randomized data. Factors influencing substandard gynecologic cancer for American women include the following: (1) the unregulated nature of the American health care system, (2) failure of professional education related to training in surgical principles and techniques and referral practices, (3) inadequate interactions between subspecialists and referring physicians, (4) disincentives for physicians to refer patients out of managed care networks or group practices, (5) disagreements between clinicians representing competing disciplines, and (6) conflicts of interest on the part of academic physicians or cooperative groups. Recommended initiatives include the following: (1) embracingthe quality of patient care as the overarching principle; (2) designing clinical trials that lead to advances in patient outcomes; (3) emphasizing public education (direct consumer information) as well as professional education; (4) partnering with local, state, and national patient advocacy groups to ensure optimal treatment for gynecologic cancers; (5) implementing practice guidelines; (6) developing referral guidelines; (7) improving communication skills of academic physicians in relating to referring physicians; (8) continuing to conduct and publish outcomes studies; and (9) establishing centers of excellence. It is time to make a commitment to substantially improving gynecologic cancer care for American women, and, I believe, the proposed initiatives will begin to accomplish this essential goal. PMID- 11769856 TI - Improving the human side of cancer care: psycho-oncology's contribution. AB - Psycho-oncology is only about twenty-five years old, emerging since the diagnosis of cancer began to be revealed and honest discussions could occur about this illness. The stigma has diminished and much progress has been made in that short period. This small new field brings concepts to care that incorporate both prevention and delivery of services to reduce distress and enhance well-being. Its first dimension studies the psychological reaction of patients at all stages of the disease, as well as those of the family and healthcare staff, and the second dimension explores the psychological, social, and behavioral factors that may impact on cancer incidence and survival. Psycho-oncology has a place at the table within the oncology community, both in clinical care and in research, especially related to prevention, quality of life, symptom control, and palliative care. Psycho-oncology is part of the continuum of cancer care that includes primary and secondary prevention at one end, and survivors and palliative care at the other. Our present body of information rests on a large database of research. Implementation of what we know now could greatly improve the psychological well-being and quality of life of patients with cancer. PMID- 11769857 TI - The concept of a planned neck dissection is obsolete. PMID- 11769858 TI - Rheumatologic disorders and radiotherapy. PMID- 11769859 TI - Minimizing cardiotoxicity following breast radiotherapy: treatment planning is the key. PMID- 11769860 TI - Breast-conserving therapy in the setting of collagen vascular disease. AB - BACKGROUND: It is unclear whether the presence of collagen vascular disease should be considered a contraindication to irradiation. This study was undertaken to determine whether women with pre-existing collagen vascular disease have an increased incidence of complications after breast-conserving therapy. METHODS AND MATERIALS: A cohort of 36 patients with documented collagen vascular disease was conservatively treated for early-stage breast cancer between 1975 and 1998. All of these patients were treated with conventional radiation therapy to a total medium dose of 64 Gy. Seventeen had rheumatoid arthritis; four, scleroderma; four, Raynaud's phenomenon; five, lupus erythematosus; two, Sjogren's disease; and four, polymyositis. Each of these patients was matched to two control patients without a history of collagen vascular disease on the basis of age, radiation therapytechnique, chemotherapy or hormone therapy use, tumor histology, and date of treatment. Acute and late complications were assessed using a six point scale from the toxicity criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. The scoring system for both acute and late reactions ranged from 0 (no change over baseline) to 5 (radiation led to death). For the purpose of statistical analysis, patients were classified as having a significant complication if they had a score of 3 or greater. RESULTS: With a median clinical follow-up time of 12.5 years (range, 3.0 22.5 years), no significant difference was detected between the collagen vascular disease and control groups with respect to acute complications (14% vs 8%). With respect to late complications, a significant difference was observed (17% vs 3%) between the two groups. However, when patients in the collagen vascular disease group were analyzed by specific disease, this significance disappeared in all but the scleroderma group. CONCLUSIONS: Patients with scleroderma have a statistically significant increased incidence of radiation therapy complications after breast-conserving surgery and radiation therapy. The presence of other collagen vascular diseases should not be considered a contraindication for this treatment modality. PMID- 11769861 TI - Coronary artery dosimetry in intact left breast irradiation. AB - PURPOSE: The purpose of this article is to report dose-volume histograms of coronary vessels from irradiation of the intact left breast. PATIENTS AND METHODS: Fifteen women with cancer of the left breast underwent computed tomographic treatment planning for radiation treatments of an intact left breast. Images through the heart were reconstructed at 1-mm increments to permit contouring of the coronary vessels. Five treatment plans were created for each patient; one plan from the simulated treatment fields and four additional plans that were generated from virtual treatment fields created by shifting the isocenter 5 mm and 10 mm both superficially and deep. The radiation dose was calculated using a three-dimensional treatment planning system that incorporated heterogeneity correction factors. RESULTS: With no adjustment to the perpendicular lung distance, a mean volume of 12% of the left anterior descending coronary artery received 20 Gy, 6% received 30 Gy, and 3% received 40 Gy. The dose to the left anterior descending coronary artery varied significantly with changes in the perpendicular lung distance. From the mean perpendicular lung distance of 1.87 for the simulated fields, a 5-mm increase in the perpendicular lung distance resulted in an increase of 20%, 15%, and 12% in the percentage of the left anterior descending coronary artery treated to 20 Gy, 30 Gy, and 40 Gy, respectively. With a 10-mm increase, the respective volumes were increased to 49%, 41%, and 34%, respectively. A 5-mm reduction of lung distance in the original plan resulted in a decrease of 10%, 5%, and 3% in the percentage treated to 20 Gy, 30 Gy, and 40 Gy, respectively. The dose to the left main coronary artery, the right main coronary artery, and the left circumflex coronary artery was limited to scatter and was less than 7 Gy. Changes in the perpendicular lung distance did not significantly affect the dose administered to these vessels. DISCUSSION: The left anterior descending coronary artery is anatomically located at the edge of the cardiac silhouette on traditional treatment films. Small changes in the perpendicular lung distance can significantly change the dose delivered to this vessel. A fundamental change in the shape of the dose-volume histogram occurs at a perpendicular lung distance of 2.3 cm, whereas the dose is very low when the perpendicular lung distance is less than 1.3 cm. These points may serve as clinically important values in the treatment planning for cancer of an intact breast. PMID- 11769862 TI - Elective radiation therapy for high-risk malignant melanomas. AB - PURPOSE: Local-regional recurrence rates of 30%-50% have been reported after resection of high-risk malignant melanomas (multiple node involvement, extracapsular spread, deep invasion, recurrent disease, and/or microscopically involved margins). Recently, we have been offering elective radiation therapy, after definitive surgery, to selected patients who have high-risk malignant melanomas. We herein report our initial results. PATIENTS AND METHODS: From 1993 to 1999, 40 patients who underwent surgery for high-risk malignant melanomas (multiple involved lymph nodes [21 patients]; close or microscopically involved surgical margins [nine patients]; extracapsular extension [six patients]; previously resected, recurrent disease [three patients]; and/or primary tumors more than 4 mm thick [four patients]) received elective radiation therapy. Thirty six patients received 3000 cGy in five fractions (600 cGy per fraction given twice weekly), and four patients received 3600 cGy in six fractions. RESULTS: At a median follow-up of 18.4 months (range, 3.8-74.1 months), the actuarial 5-year local-regional control rate was 84%. Systemic recurrence rates in these patients were similar to those reported for this subset of patients, and the actuarial overall survival rate at 5 years was 39%. Acute toxicity was limited to erythema of the skin and, in one instance, probable cellulitis, with no late sequelae. DISCUSSION: Elective radiation therapy (600 cGy per fraction for five or six fractions) effectively controlled residual subclinical disease after surgery; however, better adjuvant systemic therapies need to be designed to eliminate distant metastases and to alter survival rates. PMID- 11769863 TI - Validation of delayed sentinel lymph node mapping for melanoma. AB - PURPOSE: Sentinel lymph node mapping using radiolabeled tracer and blue dye is widely accepted and applied for staging melanoma. Common practice involves injection of radiolabeled tracer on the morning of surgery. However, optimal timing of radiolabeled colloid injection with respect to surgery remains debated. Injection on the day before surgery would offer the advantages of increased scheduling flexibility and decreased radiation exposure to the patient and operating room staff. We hypothesized that a single injection of radiolabeled colloid given 24 hours before surgery would be sufficient and would possibly improve intraoperative sentinel lymph node identification. PATIENTS AND METHODS: Ninety-five patients with newly diagnosed cutaneous melanoma underwent injection of radiolabeled colloid and lymphoscintigraphy 18 to 24 hours before surgery for sentinel lymph node mapping and biopsy. Sixty-three patients underwent repeat imaging immediately before surgery, and the images were compared with those obtained the previous day. Intraoperative mapping utilized a hand-held gamma probe and injection of blue dye to identify sentinel lymph nodes. RESULTS: Two hundred fifty-one sentinel lymph nodes were identified by initial lymphoscintigraphy in 95 patients. Delayed imagingwithout reinjection of radiolabeled tracer compared with the initial lymphoscintigraphy demonstrated no change (71%), clarification of initial ambiguous patterns (10%), or newly identified nodes (19%). Two hundred sixty-one sentinel lymph nodes were resected, of which 79% stained blue. Microscopic metastases were present in 20 sentinel lymph nodes (8%) in 19 patients (20%). All positive nodes contained radioactivity and blue dye. CONCLUSIONS: A single injection of radiocolloid 24 hours before surgery combined with intraoperative blue dye injection identified all sentinel lymph nodes and did not miss any metastatic disease. In addition, delayed imaging may clarify initial ambiguous findings and identify additional nodes at risk for metastasis. This technique produces sentinel lymph node identification rates, harvest rates, and rates of positivity comparable to those reported with the use of injection of radiolabeled tracer on the day of surgery and greatly facilitates the technical and administrative aspects of sentinel lymph node mapping. PMID- 11769864 TI - Accurate lymph node assessment prior to trimodality therapy for esophageal carcinoma. AB - PURPOSE: The diagnosis of esophageal carcinoma has historically been associated with a poor prognosis. Recently, investigators have reported improved outcomes for this patient population with the use of trimodality therapy. These results have fueled the debate regarding which patients may benefit from this aggressive treatment course. This retrospective analysis was conducted in order to evaluate the importance of regional lymph node involvement, determined by surgical staging before the initiation of therapy. PATIENTS AND MATERIALS: Between July 1991 and June 1999, 45 patients underwent surgical staging with thoracoscopy and/or laparoscopy followed by induction chemoradiation and surgical resection. All patients underwent consultation in our thoracic multidisciplinary clinic. Thoracoscopy included nodal sampling from American Thoracic Society levels 5, 6, 8, and 9 within the mediastinum. Laparoscopy included inspection of the liver and nodal sampling from the lesser curvature and the celiac axis. Preoperative chemoradiation consisted of two cycles of 5-fluorouracil (1000 mg/M2) and cisplatin (100 mg/M2) weeks 1 and 4 with 50.4 Gy. Radiotherapy was delivered at 1.8 Gy/fraction with 39.6 Gy being delivered to the large-field and 10.8 Gy to a small-field boost. The routine surgical procedure was an Ivor-Lewis esophagectomy performed 4 to 6 weeks after completion of induction therapy. RESULTS: The median follow up was 24 months for all patients. The median overall survival was 23 months, with 1-, 2-, and 3-year survivals of 64%, 42%, and 34%, respectively. Thirty patients had pathological evidence of lymph node disease before therapy. The pathological complete response rate for the entire group was 51%. Node positive patients had a path complete response rate of 14%, as compared with 59% for those who were NO. The median survival for these two groups was 15 months versus 35 months. Patients whose nodes were cleared by chemoradiation had a 3 year survival of 40%, whereas all patients with persistent nodal disease were dead by 2 years. Twenty-one patients have experienced recurrence of their disease. Thirteen patients had evidence of distant metastasis only, three local only, and five with both. CONCLUSION: Trimodality therapy offers patients with esophageal cancer an opportunity for long-term survival. Our experience has shown that minimally invasive pretreatment surgical staging provides useful information that can predict complete response and can help in the selection of appropriate patients for aggressive therapy. PMID- 11769865 TI - Management of craniopharyngioma. AB - PURPOSE: The management of craniopharyngioma does not have a consensus. Extensive surgery may be associated with major complications. The purpose of this study was to evaluate local tumor control and survival after limited surgery and postoperative radiotherapy. METHODS AND MATERIALS: Thirty patients with craniopharyngioma were treated at SUNY Upstate Medical University in Syracuse, NY from 1967 to 2000. The group consisted of 13 males and 17 females, and the median age was 35 years. The median follow-up was 71 months. Only two patients underwent complete tumor resection. Eighteen patients underwent subtotal resection, and 10 underwent decompressive surgery (ventriculoperitoneal shunt or cyst aspiration). Most (20/ 28) patients who had less than total resection received immediate postoperative radiotherapy. Four patients received conventional radiotherapy for recurrence. Gamma knife radiosurgery was used as part of the primary treatment in two patients and at the time of local tumor recurrence in three patients. RESULTS: The local control rate, including after salvage treatment, was 91% and 83% at 5 and 10 years, respectively. Salvage was radiotherapy, gamma knife or surgery. Ultimate local tumor control appeared better for patients who underwent subtotal resection (100% and 89% at 5 and 10 years, respectively) than for those who did not undergo resection (61% and 61% at 5 and 10 years, respectively). The overall survival was 93% and 83% at 5 and 10 years, respectively. Two patients underwent gross total resection, and one patient experienced recurrence 6 years after the surgery and was treated by gamma knife radiosurgery. Both patients are well without recurrence at 3 and 7 years after the initial surgery. Survival also appeared to be improved for the group who underwent subtotal resection (100% and 90% at 5 and 10 years, respectively) versus those who did not undergo surgery (73% and 73% at 5 and 10 years, respectively). The dose of radiotherapy > or = 50 Gy had no impact on local control or survival. Ten patients experienced surgery related complications, and five had radiotherapy-related complications, including visual, cranial nerve, motor, and endocrine deficits. CONCLUSION: The extent of surgery appears to be an important prognostic factor for predicting outcome, although this may represent selection bias. Long-term disease control is excellent after subtotal resection and postoperative radiotherapy. Encouraging initial results have been seen with gamma knife radiosurgery, and the potential for gamma knife radiosurgery to replace more extensive surgical resection should be further explored. PMID- 11769866 TI - Alessandro Agnoli Lecture. Physical chemistry in neurology: an exciting scientific adventure. PMID- 11769867 TI - Visual evoked potential abnormalities in dyslexic children. AB - Developmental reading disability (dyslexia) has traditionally been attributed to impaired linguistic skills. Recent psychophysical data suggest that dyslexia may be related to a visual perceptual deficit. A few visual evoked potential (VEP) studies have addressed this hypothesis, but their results are far from consistent. We submitted 9 dyslexic subjects and 9 age- and sex-matched normal controls to checkerboard pattern reversal VEPs. The main experimental variables were: large (0.5 cycles per degree; cpd) and small (2 cpd) checks and two reversal frequencies (2.1 Hz and 8 Hz); mean luminance and contrast (60 cd/m2 and 50%, respectively) were kept constant in all four conditions. Transient VEP (2.1 Hz) parameters did not differ between controls and dyslexics at 2 cpd. At 0.5 cpd, N70 amplitude was significantly smaller and N70 latency significantly shorter in dyslexics. Amplitudes for the fundamental frequency (8 Hz), as well as for the second and third harmonics of the steady-state VEPs were smaller in dyslexics for both stimulus sizes. A discriminant analysis correctly classified each subject. Our data confirm the hypothesis of a perceptual deficit in dyslexic subjects. The abnormalities are related to spatial and temporal stimulus frequencies: they appear when large stimuli are presented, or when the stimulation frequency is high. These data support the hypothesis of selective magnocellular dysfunction in dyslexia. PMID- 11769868 TI - Estimation of the conduction velocity of sympathetic sudomotor C fibres in healthy subjects: study of sympathetic skin reflex. AB - The aim of this study was to establish a simple method for estimating the conduction velocity (CV) of post-ganglionic sympathetic sudomotor C fibres (SSFCV) in the upper and lower limbs by simultaneously measuring the sympathetic skin reflex (SSR) in two distant sites. Fifty healthy volunteers were studied. SSRs were recorded with standard surface electrodes applied to both proximal (axilla and crural line) and distal sites for each limb (hand and foot). The CV of the efferent branch of the SSR was calculated by dividing the difference in the latencies of the response from two recording sites by the distance between the sites (axilla-hand for upper limb; crural line-foot for lower limb). Day-to day reproducibility and intra-individual variability of the SSFCV were calculated. For the upper limbs, the SSFCV in the axilla-hand tract was 2.0+/-0.3 m/sec (range 1.6-2.4 m/sec). For the lower limb, the SSFCV in the crural line foot tract was 1.4+/-0.4 m/sec (range 1.2-1.6 m/sec). Mean intra-individual variability of the SSFCV for the upper and lower limbs was 0.11 and 0.09, respectively. The coefficient of variation of the SSFCV for the upper and lower limbs was 5.1% and 5.4%, respectively. Our data show that this simple and non invasive method can reliably be used to measure the CV of the sympathetic sudomotor fibres, in suitable temperature conditions, and may be useful when investigating the physiological functions of peripheral nerves in patients with peripheral neuropathies. PMID- 11769869 TI - C2/C3 nerve blocks and greater occipital nerve block in cervicogenic headache treatment. AB - In the diagnosis of cervicogenic headache, greater occipital nerve (GON), cervical nerve, minor occipital nerve, and cervical facet joint blocks are used. In our study we compared the GON and C2/C3 nerve blocks in the diagnosis and treatment of cervicogenic headache. In both cases, repeated blocks proved to have a long-lasting effect in the treatment of this disorder, with both GON and C2/C3 blocks being found to be equally effective. PMID- 11769870 TI - Sleep complaints in periodic paralyses: a web survey. AB - Neuronal potassium conductance has been shown to influence the sleep-wake cycle and REM sleep homeostasis. The periodic paralyses (PP) are characterized by episodes of muscular weakness associated with changes in serum potassium levels and, therefore, with possible alterations in extracellular neuronal potassium conductance. We submitted a sleep questionnaire to the members of Periodic Paralysis International Listserv, an on-line support and information group for subjects with PP. Three control groups were made up of patients with untreated depression, patients with depression under treatment and healthy subjects. Both subjects with PP and those with untreated depression had a higher frequency of self-reported insufficient sleep quality and a higher number of nocturnal awakenings than patients with depression under treatment and healthy controls. PP subjects had more self-reported daytime sleepiness, sleep-related hallucinations and nightmares/abnormal dreams than the other three groups. Patients affected by PP may have disrupted sleep architecture and homeostasis. In particular, we suggest that the stereotypical abnormal dreams reported by several patients may reflect oneiric elaboration of nocturnal episodes of flaccid paralysis, while the increased frequency of sleep-related hallucinations may be due to enhanced REM sleep expression associated with alterations of neuronal potassium conductance. PMID- 11769871 TI - Cardiovascular dysfunction in parkinsonian disorders. PMID- 11769872 TI - Rehabilitation of the respiratory dysfunctions in Parkinson's disease. PMID- 11769873 TI - Urinary disorders in Parkinson's disease and multiple system atrophy. PMID- 11769874 TI - Sexual disorders in Parkinson's disease. PMID- 11769875 TI - The generation of whiplash. PMID- 11769876 TI - Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations. AB - Randomized controlled trials are generally regarded as the standard of study designs to determine potential causality. The inclusion of a placebo group in these trials, when appropriate, is generally needed to access the efficacy of a drug or dietary supplement. The recent increasing use of dietary supplements and herbal medications by patients makes it imperative to reevaluate the past findings of clinical studies. Several large-scale trials of dietary supplements have been tested in various populations to determine their effect on cancer prevention. Other trials have focused on patients already diagnosed with cancer. In the latter case, it is difficult to involve a placebo because of the serious nature of the disease. Nevertheless, much has been gleaned from these trials directly and indirectly. Overall, when analyzing primary endpoints in these trials, the results have been discouraging and even support the nonuse of certain supplements because of potential adverse effects. Other secondary endpoints in these same trials have revealed some potential encouraging and discouraging data. Individuals who currently qualify for the potential use of dietary supplements for cancer may be restricted to those who have a deficiency in a certain compound despite adequate dietary sources or lifestyle changes. Those individuals with a smoking history or other unhealthy lifestyle seem to have the most to gain or lose from taking certain dietary supplements for cancer. The time seems more than ripe to evaluate past adequate trials with supplements, such as beta-carotene, N acetyl-cysteine, selenium, shark cartilage, vitamin C, vitamin E, and others. Again, these studies have been disappointing, but they provide insight for the clinician and patient of what to potentially expect when using these supplements for cancer. In addition, indirect trials for other conditions (cardiovascular) may provide future insight into possible results for future cancer prevention trials. PMID- 11769877 TI - Current methods used for defining, measuring, and treating obesity. AB - Obesity, despite becoming a recognized epidemic in the United States and many countries around the world cannot be necessarily defined, measured, and treated in a simplified fashion. Numerous organizations have classified overweight and obesity using different anthropometric parameters. Older methods to determine the extent of obesity, such as crude weight and skin calipers, contain serious limitations. For example, measuring abdominal obesity cannot be determined using calipers. Other methods such as lean body mass, body mass index (BMI), and waist to-hip ratio (WHR) are more commonly used in epidemiologic studies but also contain inherent errors. More expensive and technologically advanced methods, such as densitometry, dual-energy x-ray absorptiometry (DEXA), and bioelectrical impedance analysis are also helpful, but the time and cost of using these methods in large-scale studies are a concern. Numerous options for treating obesity exist, and the clinician should be made aware of their strengths and limitations. Lifestyle changes are not only cost effective, but may be the best approach for individuals who desire to lose weight or to maintain their weight while becoming more fit. The addition of drug therapy is also a possibility. A variety of pharmacotherapy interventions are available to the patient on a short-term basis. In addition, two drugs have Food and Drug Administration approval for the long term treatment of obesity. Drug therapy should be viewed as adjunctive treatment to lifestyle changes for the individuals who qualify based on their BMI and other comorbidities. Drug therapy carries several adverse effects, and the potential for indefinite treatment continues to be an area of controversy. Therefore, a multidisciplinary approach to treating obesity must be considered in any patient who is obese. These treatments in combination with drug therapy in some cases have provided some of the best results in randomized trials. Obesity needs to be considered a chronic disease that requires long-term commitment and multidisciplinary treatment to achieve the desired results. Unless therapy is individualized, it may be difficult to reverse the dramatic trends in obesity rates that have been observed over the past several decades. PMID- 11769878 TI - The prevalence and effectiveness of complementary and alternative medicine: what has been learned and what it may be telling us about our patients, ourselves, and conventional medical treatment. AB - Complementary and alternative medicine (CAM) has been popular in numerous countries around the world. The fairly large range of prevalence may be partially due to different definitions of CAM from a variety of researchers, patients, and the general public. Beyond prevalence issues, few studies have specifically explored the reasons for the use of CAM. Studies that have attempted to answer this question have found that issues such as distress and quality of life issues are some partial reasons for its use. Despite the fact that few, if any, CAM therapies have prolonged survival, encouraging future research into potential benefits seems warranted because some CAM therapies have preliminary encouraging results, and overall, CAM therapies are just in need of more randomized trials. Perhaps, at this time, the central focus of studies should revolve around potential improvements in quality of life issues. Some therapies have been found to potentially improve this parameter. However, during the course of certain conventional medical treatments, many CAM therapies, such as dietary supplements, should be discouraged. These could theoretically reduce the oxidative stress caused by effective treatments, such as radiation or chemotherapy, thus reducing their efficacy. Other basic lifestyle changes, such as simple dietary changes and exercise, should be encouraged during the course of treatment because of the potential benefits already demonstrated. In addition, these simple lifestyle changes may improve overall health, which is a serious issue for many patients. The prevalence of CAM should provide a challenge to health care professionals as a call to improve already existing services and communication between patients. Rather than perceiving CAM as a potential hindrance to proper conventional treatment, the reality could be that CAM is providing a unique opportunity and insight to health care professionals on how to make our current system that much better. PMID- 11769879 TI - Obesity, interrelated mechanisms, and exposures and kidney cancer. AB - Obesity has been shown to increase the risk or be associated with numerous conditions from cardiovascular disease and type II diabetes to erectile dysfunction and osteoarthritis. Obesity may also be associated with numerous cancers, and kidney cancer or renal-cell cancer (RCC) may have one of the strongest correlations to obesity compared with cancer at any other site. Almost every epidemiologic investigation has demonstrated an association that tends to affect women more than men, but both genders are impacted. In general, past studies suggest that with increasing weight, a threshold point exists whereby a certain range of body mass index dramatically changes risk. Men and women at the most extreme ends of obesity tend to have the highest risk or only risk in past studies. Individuals at the more extreme ends of obesity may be affected by an almost indefinite number of mechanisms and exposures that could determine incidence and possibly prognosis. For example, higher estrogen levels, elevated insulin levels, a greater concentration of growth factors in adipose tissue, hypertension, cholesterol metabolism abnormalities, and immune malfunction are just some of the potential mechanisms that may increase kidney cancer risk. Obese individuals may also have lower serum levels of vitamin D and engage in less physical activity. Smoking or genetic predisposition to RCC may synergistically contribute to the effect of obesity on risk. The potential mechanisms and associations are numerous and complex. Regardless of the actual cancer risk now and in the future, the overall effect of obesity on general health is clear, and this should be kept in mind in the discussion between health professional and patient. PMID- 11769880 TI - Review of potential risk factors for kidney (renal cell) cancer. AB - Renal cell cancer (RCC) is responsible for a small percentage of total cancer cases and deaths throughout the world, but the incidence rates of RCC have been steadily increasing over the past decade, whereas numerous other cancers have stabilized or even decreased in number. Even in countries that were observed to have a lower incidence of this disease many are now experiencing large increases in the rates of this cancer. Most kidney cancers are RCC, and blacks are currently experiencing RCC rates that are higher than any other race. Older individuals are also at a higher risk compared with young individuals, but this observation may also be changing. The reasons for these potential increases are not understood beyond the partial impact and greater use of newer diagnostic procedures. Other reasons for higher rates of RCC and a better understanding of which individuals may be at the highest risk need to be examined to provide the clinician with possible clues as to who should be tested and what prevention measures should be offered. Most of the past investigations into risk factors have been case-control or retrospective studies, but some generalizations can still be made. Family history and genetics seem to increase risk, but overall are responsible for a small number of the total cases. Smoking, obesity, and even hypertension seem to be risk factors for RCC. Reducing these behaviors and conditions may also reduce the risk of RCC. Healthier eating habits (fruits and vegetables, and a lower caloric intake) and more physical activity may also reduce the risk of RCC. Therefore, it is possible that the increases in RCC may also be due, in part, to unhealthy lifestyle factors that have been on the increase over the past several decades. Recommendations for cardiovascular disease prevention should also be applied to patients or clinicians concerned about RCC risk. Finally, numerous occupations, occupational exposures, reproductive and hormonal changes or manipulations, and a variety of other factors may impact risk, but overall their contribution seems small compared with other more consistent risk factors. PMID- 11769881 TI - An introduction to aspirin, NSAIDs, and COX-2 inhibitors for the primary prevention of cardiovascular events and cancer and their potential preventive role in bladder carcinogenesis: part I. AB - Aspirin and the nonsteroidal anti-inflammatory drugs (NSAIDs) have been commercially available for decades, and their ability to reduce pain and inflammation are well known. The ability of these agents to cause adverse effects are also known, and the search for newer NSAIDs with less side effects accelerated after the two isoforms of cyclooxygenase (COX) (COX-1 and COX-2) were discovered. The selective COX-2 inhibitors seem to have equivalent efficacy, but potentially less gastrointestinal adverse effects than the traditional NSAIDs. Recent concern that the selective COX-2 inhibitors could increase cardiovascular events requires more investigation. In the meantime, aspirin continues to receive attention as a potential primary cardiovascular agent because of its antiplatelet effects and past and current clinical trials. Several trials have demonstrated that low-dose aspirin may significantly reduce the risk of myocardial infarction and other cardiovascular events. However, the benefits of aspirin need to be weighed against its primary side effect in these situations (hemorrhagic stroke). Patients at low risk for future cardiovascular events are probably not good candidates for this therapy; however, those individuals with a high risk of a future cardiovascular event may qualify for this therapy. Aspirin has also demonstrated a potential ability to reduce the risk of deep venous thrombosis and pulmonary embolism. A recent large trial of low-dose aspirin after major surgery revealed that this agent could also have some activity in the venous component of the human body. Aspirin may also have some applicability for reducing side effects of oral estrogens in men with advanced prostate cancer. Thus, it seems as if aspirin, NSAIDS, and even the selective COX-2 inhibitors may have therapeutic potential far beyond reducing pain and general inflammation. These overall observations and effects provided some of the impetus to investigate their potential ability to reduce the risk and possibly progression of a number of cancers. A few already available over-the-counter products and prescriptions seem to be receiving attention as possible anticancer agents. PMID- 11769882 TI - An introduction to aspirin, NSAids, and COX-2 inhibitors for the primary prevention of cardiovascular events and cancer and their potential preventive role in bladder carcinogenesis: part II. AB - Aspirin and the nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) have been commercially available for decades, and their ability to reduce pain and inflammation are well known. The ability of some of these agents to also reduce a primary or secondary cardiovascular event or to potentially reduce the risk of colorectal cancer has also been documented. These observations collectively have initiated a wide variety of investigations to determine whether or not these agents may have an ability to reduce the risk or progression of numerous cancers. Some urologic cancers have been included in these recent studies. For example, prostate cancer may be sensitive to these compounds based on a small number of preliminary studies. Bladder cancer may also be sensitive to the effects of these agents. Older patients and those with more aggressive tumors may benefit most from these initial studies. Many cancers also demonstrate a greater upregulation of cyclooxygenase-2 (COX-2), and this has lead to recent interest, especially in colorectal cancer, to test the ability of these selective agents against the development of precancerous colon polyps. High-risk patients for colorectal cancer may have benefited by taking a selective COX-2 inhibitor in a recent randomized trial, but whether or not this benefit continues to occur after the COX-2 inhibitor is removed remains controversial and needs further study. Prostate and bladder cancer also seem to demonstrate an upregulation of COX-2, and laboratory studies suggest that these selective NSAIDs may have a greater effect on reducing the development of these tumors. Randomized clinical trials are needed, but because numerous individuals are currently using COX-2 inhibitors, a large volume of data should make at least retrospective studies more plausible in the near future. The challenge for researchers and clinicians is to further understand which NSAIDs and what dosage and duration may provide the optimal benefit (if any), and to accurately construe the available current data on these agents for patients inquiring about these compounds. PMID- 11769883 TI - Dynamometer measurements of hand-grip strength predict multiple outcomes. AB - Hand-grip strength, which can be measured easily and objectively using a dynamometer, is predictive of multiple outcomes among a variety of subjects. Although the literature is not fully consistent, it tends to support grip strength as a predictor of postoperative complications, mortality, and functional decline. Hand-grip dynamometry may merit broader application as a screening procedure. PMID- 11769884 TI - Cell-mediated immune hypersensitivity is stronger in the left side of the body than the right in healthy young subjects. AB - More frequent appearance of herpes zoster infection on the left side of the body has been noted. In women, breast cancer occurs more frequently on the left side. It has been suggested that the left neocortex is involved in neuroimmunomodulation via the dopaminergic system. In this study, our purpose was to investigate the possible difference in cell-mediated hypersensitivity between right and left body sides using the tuberculin test with 22 male and 36 female healthy high school students. In the present study, the cell-mediated hypersensitivity was higher in the left side of the body than the right. This difference was slightly more apparent in the girls and may be related to brain asymmetry in neuroimmunomodulation. PMID- 11769885 TI - Cognitive subprocesses of mental rotation: why is a good rotator better than a poor one? AB - The Vanderberg-Kuse Mental Rotation Test is a standard test of mental rotation ability. Recent experiments have demonstrated that mental rotation is a complex cognitive process wherein different subprocesses (focused attention, visual scanning, perceptual decision, visual memory) play important roles in performance. We classified the population as good and poor rotators by performance of mental rotation (ns = 47: 22 men and 25 women, respectively; mean age: 20.7 yr.). To examine differences cognitive subprocesses of mental rotation of these two groups were compared. There were significant differences between poor and good rotators in performance on Raven's test and the Pieron Focused Attention test scores. The good rotators scored better because their perceptual decision-analytical intelligence (Raven) and focused attention scores were higher. PMID- 11769886 TI - Correlates of regional suicide and cancer mortality rates. AB - Regional mortality rates from cancer and suicide had similar social correlates in the Ukraine but not in the United States. PMID- 11769887 TI - Learning and transfer in two perceptual-motor skills in Duchenne muscular dystrophy. AB - The present study examined perceptual-motor learning and its bilateral transfer in Duchenne muscular dystrophy. which is well known as a genetically determined disorder in which muscles gradually degenerate and weaken across age. Mirror tracing and rotary-pursuit tasks were used to measure perceptual-motor performance in 18 patients with and 28 without (control subjects) the disorder. The results of two experiments indicated that the patients showed learning basically similar to most of the controls. Relatively low performance of these patients seemed to be associated with their kinetic disability, not by deterioration of the mediating process in perceptual-motor coordination. PMID- 11769888 TI - Comparison and reliability of three goniometric methods for measuring forearm supination and pronation. AB - Active supination and pronation range of motion of the right forearm by 10 men and 21 women were measured with a goniometer using three methods. For Method One the moveable arm was aligned with a pencil held in the hand; for Method Two the moveable arm was placed over the anterior and posterior surface of the distal forearm for supination and pronation, respectively; and for Method Three the moveable arm was aligned parallel with a visualized line connecting the distal ulna and radius. Supination range of motion was greatest for Method One, followed by Methods Three and Two, respectively. Pronation range for Method One was less than for the two other methods. Intraclass correlation coefficients ranged from .81 to .97 for three trials within the test session and from .86 to .96 between the test and a 1-hr. retest session for both actions using all three methods. Method One was the most reliable but appeared invalid for measuring supination because of movements of the 4th and 5th metacarpal bones. Methods Two and Three appeared appropriate for clinical application but not interchangeable. PMID- 11769889 TI - Does "pure" phonemic awareness training affect reading comprehension? AB - The six studies found concerning the effect of pure phonemic awareness training (without phonics) on reading comprehension gave a positive but modest overall effect size in favor of phonemic awareness training. Four studies had small samples, two showed no or very small effect sizes, and one inconsistent results. Three involved languages other than English. Such results do not support the popular movement for universal phonemic awareness training. PMID- 11769890 TI - Game location and officiating bias in English Club Cricket. AB - One potential contributing factor to the commonly observed home advantage in competitive sport is that officials may be biased in favour of the home team as a result of pressure from spectators. The present study examined officiating behaviour and home advantage, defined as home teams winning over 50% of decided games in English Club Cricket, a sport virtually devoid of spectator influence. Records of game outcomes, as well as dismissals requiring a decision by the umpire, were analysed. The relative frequency of umpiring decisions did not favour either home or away teams. However, a home advantage was found, with the home teams winning 57.1% of decided games (n = 1.449). Considered together, the results suggest that in sports with little or no spectator influence teams may win more often at home for reasons other than biased umpiring decisions, such as familiarity with their home ground or a visiting team's fatigue following travel. PMID- 11769891 TI - Tactual performance test trials: internal consistency reliability using the Gilmer-Feldt coefficient. AB - Internal consistency reliabilities using the Gilmer-Feldt coefficient were calculated for the Tactual Performance Test for the Preferred Hand (n=298), Nonpreferred Hand (n = 302), and Both Hands (n = 314) trials, and total time. Reliabilities were reported for the total sample and three groups: 118 normal volunteers, 95 inpatient alcoholics, and 103 undiagnosed patients sent for neuropsychological assessment. The reliabilities ranged from .5584 to .8953. PMID- 11769892 TI - Examination performance and graphological analysis of students' handwriting. AB - Research has yielded mixed support for graphological claims. The present study was designed to see whether specific components of students' handwriting were related to personality traits associated with achievement in written examinations. If aspects were identified that could be used to predict future academic performance, the findings would not only be of interest to graphologists but would be invaluable to both student and tutor in a teaching environment. In a blind trial, 100 handwriting samples from first-year scripts were analysed for the presence or absence of 12 graphological characteristics deemed to be relevant for academic performance, and each of these aspects was tested for association with the grade points awarded. Statistically significant differences were found for two of the 12 characteristics: "carefulness" and "constancy." Also, measurements of individual letters indicated that consistent slant was significantly associated with high grade points, whereas upright or mixed writing was not. These attributes appeared to be generally related to readability and aesthetic quality. Although such aspects might influence the grading of scripts by teachers, typed versions received similar grades to those awarded for the handwritten versions. PMID- 11769893 TI - Do competitive martial arts attract aggressive children? AB - The purpose of the present study was to ascertain whether children beginning martial arts training were more aggressive than their peers. 150 8-yr.-old children were administered the Buss-Perry Aggression Questionnaire. Analysis showed that children beginning martial arts training did not score more aggressive than their peers but scored higher on the Anger scale. This difference, however, appeared only in children practicing judo. PMID- 11769894 TI - Properties of internal speed control and psychophysiological response during continuous forearm rotation movement. AB - This study investigated the properties of speed control and psychophysiological response when subjects changed movement speed internally. The task consisted of a continuous forearm rotational movement, which 14 women performed under 3 conditions, namely, (1) Preferred: the subject performed the task at a freely selected speed, (2) Slow: the subject changed the speed in two steps from preferred to a slower pace (slow, then very slow), (3) Fast: the subject changed the speed in two steps from preferred to a faster pace (fast, then very fast). Rotation speed and the coefficient of variation were measured to evaluate within subject variability. Under the Preferred condition, there were no significant differences in rotation speed or coefficient of variation during the trials. However, under Slow and Fast conditions, the standard variation scores and coefficient of variation indicated different tendencies. Under the Fast condition, although the standard variation increased with the faster speed, the coefficient of variation decreased. On the other hand, the coefficient of variation increased under the Slow condition. Preferred speed had a significant positive relationship to the slow, very slow, fast, and very fast speeds. Heart rate (R-R interval) and EEG spectral intensity measurements showed no significant changes among the three conditions: however, respiration frequency significantly increased during Fast as compared to Preferred and Slow conditions. These results suggest that a preferred speed for continuous movement exists and that it is closely related to internal speed control as a psychological criterion. Furthermore, different movement speeds may reflect different psychophysiological responses. PMID- 11769895 TI - Blood lactate recovery and perceived readiness to start a new run in middle distance runners during interval training. AB - The aim of this study was to establish to what extent ratings of perceived readiness to start a new run are dependent on recovery of blood lactate and heart rate during passive recovery between interval runs (4 x 2000 m) of increasing intensity by 15 male college-level middle-distance runners. The Perceived Readiness Rating scale was administered at each minute of recovery. Blood lactate concentration was measured immediately after runs at Min. 3 of recovery after the first and second runs, and, in addition, at Min. 6 of recovery after the third and fourth runs. Heart rate was recorded continuously during the runs and during recovery. The obtained correlation between blood lactate recovery and perceived readiness ratings after the third and fourth runs were -.36 and -.56, respectively (p<.05). Consequently, blood lactate concentration recovery appears to influence the middle-distance runners' perceived readiness estimation to begin a new run. The Perceived Readiness Rating applied by us appears useful in the training of middle-distance runners. PMID- 11769896 TI - Evaluation of the offensive behavior of elite soccer teams. AB - The purpose of the present study was to evaluate the offensive behavior of the four elite teams (France, Brazil, Croatia, and Holland) using data from the semifinals of the 18th World Soccer Championship in France in 1998. 28 videotaped soccer games were observed, 7 for each team. The protocol contained the following parameters of evaluation: (a) successful pass in the defensive and middle area, (b) unsuccessful pass in the defensive and middle area, (c) attempt on goal in the offensive area, and (d) cross and follow-up action. A multivariate analysis of variance showed the teams' plan was significantly different only in playing the ball back to the goalkeeper. This last action, used more often by Holland than by the other teams, indicated its restrained offensive behavior, which may be one of the reasons for its defeat in some games. PMID- 11769897 TI - Are neo-Piagetian and neo-Vygotskian interpretations of potential for learning complementary? AB - According to Pascual-Leone, potential for learning in the neo-Piagetian framework complements the neo-Vygotskian framework for assessment of learning potential, a manifestation of the child's zone of proximal development. Data obtained in a 1998 study by Niaz and Caraucan with three groups of children (7- to 10-yr.-olds, N=94) are reinterpreted as showing the two interpretations are complementary. PMID- 11769898 TI - Accuracy of movement speed and error detection skills in adolescents with cerebral palsy. AB - People with cerebral palsy (CP) usually have decreased ability to learn new movements and decreased movement speed. This study examined the ability of 10 adolescents with CP (M age = 16.2 yr., SD = 1.9 yr.) to achieve a target speed on an tipper extremity ballistic task and to detect speed errors in their movements, compared to the performance of 10 adolescents with no disability (M age = 15.7 yr., SD = 1.7 yr.). Subjects were instructed to slide a lever along a track in 150 msec., then guess their movement time. Knowledge of results feedback was provided on the first 50 trials except for Trials 11-20 on Day 1. Knowledge of results feedback was withheld on Day 2, Trials 51-60, to assess learning and retention of the skill. Speed Error and Error Detection were compared for two groups of adolescents on Trials 51-60. Independent t tests indicated a significant difference between the two groups for both Speed Error and Error Detection. Examination of individual scores of the adolescents with CP indicated that half scored within the range of the control group, and variability of skills within the group with CP was high. Some individuals with CP have deficits in accuracy of movement speed and error detection unrelated to their severity of CP which may affect their ability to learn new movements. PMID- 11769899 TI - Factors affecting subjective estimates of magnitude: when is 9 > 221? AB - 112 undergraduates separately judged the size of the numbers 9 then 221 or 221 then 9 on a 10-point scale or on a continuous line that were both anchored only at the extremes by "very, very small" and "very, very large." Replicating the 1999 Birnbaum study, 9 was given a higher rating than 221 when the numbers were judged first by different people on the numerical scale. However, 9 was given a similar or smaller rating than 221 in the other conditions. The results are discussed in terms of context effects. PMID- 11769900 TI - Geophysical variables and behavior: XCVI. "Experiences" attributed to Christ and Mary at Marmora, Ontario, Canada may have been consequences of environmental electromagnetic stimulation: implications for religious movements. AB - Since the year 1992 individuals and groups of people have reported religious experiences near Marmora, Ontario, Canada. The experiences, attributed to Christ or Mary, have occurred near the top of a hill adjacent to an open pit magnetite mine that has been accumulating about 15 million gallons of water per month for more than a decade. During the period between 1992 and 1997 epicentres for local seismic events moved significantly closer to this site. Most of the messages attributed to spiritual beings by "sensitive" individuals occurred one or two days after increased global geomagnetic activity. We suggest that conditions produced by local geophysical and geological properties created the odd lights and induced physiological changes within the thousands of people who visited the area. Direct measurements indicated that weak (0.1 microTesla to 1 microTesla) complex magnetic fields, the temporal patterns of which were similar to the experimental fields we have employed to evoke the sensed presence and altered states within the laboratory, may have been generated within the area. PMID- 11769901 TI - Intrinsic and extrinsic motives for originally following a sport team and team identification. AB - Research indicates that both highly and lowly identified fans are more likely to be intrinsically than extrinsically motivated and that highly identified fans have a particularly strong inclination for intrinsic motivation. The current investigation was designed to extend this work by examining the relationship between level of identification and one's intrinsic and extrinsic motives for originally following a sport team. Preference for intrinsic motives for originally following a team should be highest among those high on team identification. 88 participants completed questionnaires containing the Sport Spectator Identification Scale and items assessing their intrinsic and extrinsic motives for originally identifying with a team. Analyses provided clear support for the hypotheses. PMID- 11769902 TI - Eye colour and reaction time to visual stimuli in rugby league players. AB - Subjects with dark eye colour are thought to perform better on reactive tasks in comparison to light-eyed subjects, whereas light-eyed subjects show enhanced performance over dark-eyed subjects on self-paced activities. This study examined reaction time using unrestricted and peripheral vision and success at the self paced activity of goal kicking in 59 elite male Rugby League players. Subjects with dark eye colour did not react significantly faster than the light-eyed subjects when tested using unrestricted vision or peripheral vision. Examination of the self-paced activity of goal kicking showed that the percentage success rate was not significantly higher in the light-eyed group than the dark-eyed group. In conclusion, there was no significant difference in reaction time to a visual stimulus or success in goal kicking between dark- and light-eyed Rugby League players. PMID- 11769903 TI - Use of primary and secondary reinforcers after performance of a 1 mile walk/run by boys with attention deficit hyperactivity disorder. AB - Based on visual inspection of time (sec.) across 8 exercise sessions for each, 3 reinforcement techniques of mainly token exchange and verbal praise paired with token exchange, were mildly associated with improvement of the cardiovascular performances of 5 young boys with ADHD. Specific reinforcement techniques improved time for this 1-mile walk/run by 5 boys with ADHD. PMID- 11769904 TI - Peripheral vision and back tuck somersaults. AB - Although vision appears to enhance performance of somersaulting skills, few studies have investigated the source (foveal or ambient) of useful visual cues that can potentially be used by gymnasts during a somersault. Therefore, the primary objectives were to investigate the possible role of peripheral vision in the control of orientation and landing balance in a back tuck somersault. 10 female gymnasts (age = 11.6 +/- 2.7 yr., competitive level = 8 +/- 1.2, training time in gymnastics = 5.9 +/- 1.6 yr.) performed back tuck somersaults under four visual conditions (full visual field, horizontal peripheral vision limited to 100 degrees, horizonal peripheral vision limited to 60 degrees, and no vision) while wearing electromagnetic sensors that allowed automatic digitizing. Analysis yielded no statistically significant difference on any of the kinematic variables among vision conditions. Despite limiting the gymnasts' available horizontal peripheral vision, joint angles, angular velocities, and timing remained very similar. There were no statistically significant differences in landing balance between the conditions of full vision, 100 degrees peripheral vision, and 60 peripheral vision. However, gymnasts were less stable at landing when vision was absent as compared to the three other vision conditions. PMID- 11769905 TI - Verbal categories for classification of spinal postures and their respective angular values registered by photographs and electrogoniometry. AB - The perception of posture may allow workers to discern sensations associated with physical overload and potential tissue damage. In an occupational context, the classification of body postures in ranges of amplitude has been useful for researchers and ergonomists interested in evaluating the exposure of workers to uncomfortable and potentially harmful postures. In this paper we describe measurements, using photographs and electrogoniometry of the angle of flexion of the trunk and of the thoracolumbar segment, respectively, adopted according to the verbal categories of mild, moderate, and severe flexion, as requested by the experimenter. The results showed no differences between the groups of subjects, but significant differences occurred in the classification of the movement amplitude per verbal categories. PMID- 11769906 TI - Relation of rifle stock length and weight to military rifle marksmanship performance by men and women. AB - 15 male and 13 female soldiers participated in a study to examine the effects of sex, rifle stock length 117.8 cm, 22.3 cm, and 26.2 cm), and rifle weight (3.2 kg vs 3.8 kg) on military marksmanship performance. The Noptel simulator was used to assess marksmanship accuracy (proximity of shots to the target center) and precision (proximity of shots to one another regardless of proximity to the target center). There were no significant differences in either measure of marksmanship performance as a function of sex. Marksmanship accuracy was significantly better with the shortest rifle stock, and marksmanship precision was significantly better with the lighter rifle. Regardless of the sex of the shooter, stock length and weapon weight should be considered in any new combat rifle design as these results indicate they significantly affect marksmanship. PMID- 11769908 TI - A cognitive-perceptual analysis of projective tests used with children. AB - There are both general and specific problems with projective tests--the production, comprehension, and interpretation of two-dimensional visual representations. At the general level, there is a need to integrate findings from the neuro- and cognitive sciences, cognitive, perceptual, and affective development, and the understanding and interpretation of pictorial material based on the accumulated research base in the arts. At the specific level, much of the research base on projective tests is poor or outdated; evidence for clinical utility is mixed or negative; and the tests possess poor reliability and validity while the putative underlying psychological process of projection" has not been subject to rigorous empirical examination--the term remains vague and elusive. While earlier critiques and reviews have focused on problems in validity and reliability, their has been a lack of attention to the development of children's pictorial abilities as pertain to projective techniques. Although many of the principles delineated here also apply to adolescents and adults, an important challenge for clinicians is to develop and employ better methods in the "projective" assessment of children. PMID- 11769907 TI - A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction. AB - This study investigated the biological basis of visual processing disabilities in adults with Chronic Fatigue Syndrome. The study involved 61 adults with symptoms of Chronic Fatigue Syndrome who were screened for visual processing problems (Irlen Syndrome) and divided into two groups according to the severity of symptoms of Irlen Syndrome. Significant variations were identified in blood lipids and urine amino and organic acids of the two groups, which may be indicative of activation of the immune system due to some infective agent. It was suggested that metabolic profiling may help the development of more valid diagnostic categories and allow more investigation of immune system dysfunction as a possible causal factor in a range of learning and behaviour disorders. PMID- 11769910 TI - On the reality of the incorporeal intelligibles: a reflection on the metaphysics of psychology. AB - An argument is made for the existence of entities which are neither necessarily material nor mental as real and which are apprehensible and generatable by human beings. Money, color, triangle, natural and social law, instruction, danger, and invention are given as examples. It is the task of the science of psychology to grasp, conceptualise, and characterise the human being that lives in a world of incorporeal intelligibles and makes them as well. The tradition of Aristotle, Brentano and his two students, Freud and Husserl, and Wertheimer is identified favorably in this connection. PMID- 11769909 TI - Role of motor imitation in traversability of surfaces by walking infants. AB - The ecological approach by Gibson stressed the role of visual cues in toddlers' locomotor activities. In particular, a rigid surface offers more traversability "affordances" to walkers (13-16 mo. old) than a deformable surface. On the other hand, imitation plays a relevant role in human behaviors. In our study a group of 17 walking infants (12-19 mo.) were asked to choose between locomoting on a rigid versus a deformable surface after having seen an older child walking on the deformable surface. A control group of 19 infants were asked to do the same task without having seen a model. The task was repeated three times. No relevant differences appeared between the two groups as to the choice of surfaces: the rigid surface was preferred by both groups. Some slight differences in the behavior of the experimental group were seen as a result of observing the model. Clearly, however, social stimulus. such as the sight of an older child performing a specific task, does not overcome the affordances which induce infants not to walk on the deformable surface. PMID- 11769911 TI - Response selection and execution skills of professionals and novices during singles tennis competition. AB - This study extended research on sport expertise concerning the development of cognitive and motor skills in singles tennis (McPherson, 1999). 12 adult male professional and novice tennis players were videotaped during singles competition. Opponents for matches were randomly selected within each group of participants. Two tennis experts utilized an observational scale to judge players' performance generated during competition for serves and shots following the serve, e.g.. return of serves, lobs. Each player was scored on three performance components: quality of movement to or control of the ball for serves or shots attempted (control skills), appropriateness of serve or shot selections in the context of game situations (response selection skills), and quality of serves or shots produced (response execution skills). Relative frequency scores for the highest category of each performance component were derived according to the number of opportunities to respond. Serve performance indicated both groups were able to control their serves: however, professionals made more tactical selections and forceful executions. Shot performance indicated professionals made more successful movement to and control of shots, tactical shot selections, and forcing shot executions than novices. Overall, players' tactical response selections were greater than their forceful response executions. Thus, assessing players' decisions during competition may provide vital information concerning tactical skill development. Further, professional players exhibited higher and more consistent tactical behavior than elite collegiate players examined in 1999 by McPherson. Findings were attributed to tactical knowledge and motor skill development resulting from competition and practice experiences. PMID- 11769912 TI - Independence of timing and force control during finger-tapping sequences by pianists. AB - To examine the relation between timing and forcc control during finger-tapping sequences by both the 10 pianists and the 13 nonpianists, participants tapped a force plate connected to strain gauges. A series of finger-tapping tasks consisted of 16 combinations of pace and peak force. Analysis showed that pianists had smaller correlation between intertap interval and peak force than nonpianists. Thus, force control was more independent of timing for pianists than for nonpianists. PMID- 11769913 TI - Physical fitness and self-reported physical exercise among college men and women in 1987 and 1997. AB - The study examined the relations of self-reported physical activity levels and physical fitness scores for two samples of college students assessed in 1987 (n = 261) and in 1997 (n = 243). Significantly greater exercise was reported by the 1997 women than the 1987 women; amount of exercise reported by men did not differ. For both samples, greater exercise was associated with increased fitness for women and men as assessed by the Hall 1986 Physical Fitness Test Profile, comprised of measures on body fat composition; grip strength; muscle endurance, flexibility, resting heart rate; systolic and diastolic blood pressures; and aerobic power. For the 1987 sample men were more fit than women. For the 1997 sample, women were more fit than men. The 1997 women were more fit than the 1987 women; there was no difference on overall fitness measures of the two samples of men. PMID- 11769914 TI - Effects of time and movements of the preshot routine on free throw shooting. AB - This study examined the effects of length and movements of preshot routines on free throw shooting in basketball. 17 members of an intercollegiate men's basketball team attempted 20 free throws in each of four different conditions: (1) normal routine and time, (2) normal routine with altered time, (3) altered routine with normal time, and (4) altered routine with altered time. Free throw performance was measured using an objective 5-point scoring system. A multivariate analysis of variance indicated a significant effect for routine. Neither time nor routine by time was significant. Results indicated that altering the movements in the routine had a significant effect on performance while lengthening the time did not. PMID- 11769915 TI - Regional variation of divorce in Poland. AB - Divorce rates in Polish counties in 1998 were predicted by death rates, percent urban, females/males, and outmigration. PMID- 11769916 TI - How useful is on-mountain sonography? PMID- 11769917 TI - The electrocardiogram in hypothermia. AB - OBJECTIVE: Hypothermia is known to adversely affect the electrocardiogram (ECG) in many cases. This study set out to determine the incidence of defined cardiac dysrhythmias, J waves, and conduction abnormalities in urban hypothermia. METHODS: A prospective, multicenter study was carried out to determine the incidence of defined cardiac rhythms in patients suffering from accidental urban hypothermia. The ECGs were independently analyzed by 2 of the authors and placed into 1 of 6 rhythm categories. RESULTS: Seventy-three ECGs were analyzed. Normal sinus rhythm was the most common rhythm (41%). Overall mortality was 36% (26/73). J waves occurred in 36% of survivors and 38% of non-survivors and were, therefore, not prognostic. Shivering artifact was present in 66% of survivors and 38% of nonsurvivors. Although there was no statistically significant association between J waves and survival (P = .21), the presence of shivering artifact was associated with survival in severe hypothermia (P = .047). Atrial fibrillation and junctional bradycardia were both associated with high mortality. CONCLUSIONS: This study confirms that the ECG is abnormal in the majority of patients suffering from accidental hypothermia. J waves do not appear to be independently prognostic in hypothermia. The results suggest that the inability to mount a shivering response may be associated with a poorer outcome; this finding requires further study. PMID- 11769918 TI - A comparison of carbon monoxide levels during the use of a multi-fuel camp stove. AB - OBJECTIVE: The use of camp stoves in an enclosed or poorly ventilated space is clearly not recommended due to the risk of carbon monoxide (CO) poisoning. Instances may arise, however, when use for a limited time is necessary. We sought to find differences in CO levels between various fuels used to power a commercially available camp stove. METHODS: A comparison was made between unleaded gasoline, kerosene, and white gas (Coleman fuel). The stove, fuels, and CO detector were all purchased from local retailers. A 0.4-m3 space was constructed with a cardboard box. Three trials were performed using each fuel in which water was heated over the stove for 5 minutes. Measurement of the CO level within the box was taken every 30 seconds. RESULTS: Kerosene created CO levels of 714 (SD = 113.5) parts per million (ppm) at 2 1/2 minutes but was out of the measurable range of >999 ppm within 4 minutes on each of its trials. White gas burned the cleanest, with an average of 212 ppm (SD = 27.8) at 2 1/2 minutes and 348 ppm (SD = 76.0) at 5 minutes. Unleaded gasoline created 305 ppm (SD = 27.1) at 2 1/2 minutes and 464 ppm (SD = 31.6) at 5 minutes. CONCLUSION: All of the fuels created a high level of CO in a short period of time. White gas burned the cleanest and would be preferred to unleaded gasoline or kerosene in the event that the unvented use of a camp stove was necessary. PMID- 11769919 TI - Rabies exposures in thai children. AB - OBJECTIVE: To determine the epidemiology of potential rabies exposures in Thai children. METHODS: The study was carried out at the Queen Saovabha Memorial Institute of the Thai Red Cross Society during I calendar year. All charts of victims aged 0 to 14 years with possible rabies exposures were retrospectively reviewed. RESULTS: Subjects were 2622 children, with a male to female ratio of 1.6:1 and a mean age of 6.7 years (range, 2 months to 14 years). Most exposures (86.3%) were related to dogs. The most common site of exposure was the lower extremity. The majority of exposures occurred in or around the home and as the consequence of unprovoked attacks rather than provoked attacks. Antirabies vaccines were given in all cases: 68.4% using the Thai Red Cross intradermal route, and 31.6% using the intramuscular route. Rabies immunoglobulin (RIG) was prescribed in 57.5% of children; 35.2% received human RIG (HRIG), and 22.3% received purified equine RIG (ERIG). CONCLUSIONS: This study confirms that rabies exposures, especially in children, are an important public health problem in Thailand. The reduced-dose, multiple-site intradermal rabies vaccine method and ERIG in place of HRIG reduce the cost of treatment. PMID- 11769920 TI - Avalanche trauma and closed head injury: adding insult to injury. AB - OBJECTIVE: The incidence of fatal closed head injury (CHI) and nonfatal CHI causing an altered level of consciousness in avalanche victims is unknown. The purpose of this study was to assess the incidence and potential significance of CHI in avalanche-related deaths. METHODS: The records of the state medical examiner and hospital records of all victims killed in avalanches in the state of Utah from October 1, 1992 through April 30, 1999 were reviewed for a cause of death and for the presence of CHI. Closed head injury was described as "present" or "severe," depending on whether the degree of CHI was sufficient to have caused or directly contributed to death, as determined by the medical examiner. RESULTS: In this review, 28 avalanche-related deaths were identified, of which 22 (79%) were due to asphyxia. Seventeen victims (61%) had evidence of some degree of CHI. Six victims (21%) had evidence of severe CHI. One of 7 snowmobile riders sustained a severe CHI, whereas 4 of 16 skiers or snowboarders sustained a severe CHI (P = not significant). CONCLUSION: Although asphyxiation was the cause of death in most avalanche victims, evidence of CHI was present in 61% of the cases studied. While avalanche-associated CHI may not be sufficient to cause death in many cases, a depressed level of consciousness might render a victim incapable of self-rescue and predispose to asphyxia. Helmet use may help prevent avalanche associated CHI and thus be a useful safety adjunct. PMID- 11769922 TI - Normal oxygenation and ventilation during snow burial by the exclusion of exhaled carbon dioxide. AB - OBJECTIVE: To confirm that the accumulation of exhaled carbon dioxide (CO2) is the principal cause of nonmechanical asphyxiation during avalanche burial by demonstrating that complete exclusion of exhaled CO2 during experimental snow burial results in normal oxygenation and ventilation utilizing the air within the snowpack. METHODS: In the experimental group, 8 healthy volunteers (mean age 32 years, range 19-44 years) were fully buried up to 90 minutes in compacted snow with a density ranging from 300 to 680 kg/ m3 at an elevation of 2385 m. The 6 men and 2 women breathed directly from the snow utilizing a device containing no air pocket around the inhalation intake, in addition to an extended exhalation tube running completely out of the snowpack to remove all exhaled CO2. Continuous physiologic monitoring included oxygen saturation, end-tidal CO2, inspired CO2, electrocardiogram, rectal core temperature, and respiratory rate. As controls, 5 of the 8 subjects repeated the study protocol breathing directly into a small, fist-sized air pocket with no CO2 removal device. RESULTS: In the experimental group, the mean burial time was 88 minutes, despite the absence of an air pocket. No significant changes occurred in any physiologic parameters in this group compared to baseline values. In contrast, the controls remained buried for a mean of 10 minutes (P = .003) and became significantly hypercapnic (P < .01) and hypoxic (P < .02). CONCLUSIONS: There is sufficient oxygen contained within a densified snowpack comparable to avalanche debris to sustain normal oxygenation and ventilation for at least 90 minutes during snow burial if exhaled CO2 is removed. The prolonged oxygenation observed during CO2 exclusion is irrespective of the presence of an air pocket. PMID- 11769921 TI - Retrospective study of 70 cases of severe frostbite lesions: a proposed new classification scheme. AB - OBJECTIVE: Previous frostbite classifications were mainly based on retrospective diagnosis and, most of the time, could not be used to predict the final outcome of the lesions and especially the probability of an amputation and its level. The aim of this study was to suggest a new classification at day 0 based mainly on the topography of the lesions and on early bone scan results, which are more convenient and accurate in predicting the final outcome of frostbites. METHODS: The retrospective study of the clinical histories of 70 patients hospitalized at Chamonix Hospital (Mont-Blanc Massif) from 1985 to 1999 for severe frostbite injuries of the extremities has allowed us to classify the aspects of the initial lesions on day 0 and to compare them with final outcomes. RESULTS: A strong correlation was found between the extent of the lesion and the outcome of each finger or toe. When the initial lesion was on the distal phalanx, the probability of bone amputation was around 1% for the digit, 31% for the middle phalanx, 67% for the proximal phalanx, 98% for the metacarpal/metatarsal, and 100% for the carpal/tarsal. CONCLUSIONS: Based on these clinical results and on the results of bone scans (previously validated), a new classification of frostbite severity at day 0 is proposed. Four degrees of severity are defined: first degree, leading to recovery; second degree, leading to soft tissue amputation; third degree, leading to bone amputation, and fourth degree, leading to large amputation with systemic effects. PMID- 11769923 TI - A brief case report and review of ciguatera poisoning. AB - Although ciguatera fish poisoning is generally a mild, self-limited disease, both life-threatening acute reactions and troublesome chronic symptoms can occur. Because ciguatera has been largely confined to tropical locations, a relative lack of recognition exists among many US physicians. As access to tropical locations has increased, so has the distribution of ciguatera. Herein, we present a case report and review the current literature on ciguatera. PMID- 11769924 TI - Hand-held portable sonography for the on-mountain exclusion of a pneumothorax. PMID- 11769925 TI - Challenging paradigms is risky business: reflections on C. C. Snyder's "A definitive study of snakebite" --a commentary. PMID- 11769926 TI - A definitive study of snakebite. 1968. PMID- 11769927 TI - Acetazolamide (diamox) may cause frostbite at extreme altitude. PMID- 11769928 TI - The geography of health and the making of the American West: Arkansas and Missouri, 1800-1860. PMID- 11769929 TI - Geography, race and nation: remapping "tropical" Australia, 1890-1930. PMID- 11769930 TI - Humboldtian representations in medical cartography. PMID- 11769931 TI - The first global map of the distribution of human diseases: Friedrich Schnurrer's 'Charte uber die geographische Ausbreitung der Krankheiten' (1827). PMID- 11769932 TI - Heinrich Berghaus's map of human diseases. PMID- 11769933 TI - Airs, waters, places: perennial puzzles of health and environment. PMID- 11769934 TI - Medical science before scientific medicine: reflections on the history of medical geography. PMID- 11769935 TI - Histories of medical geography. PMID- 11769936 TI - The geographical imperative in nineteenth-century French medicine. PMID- 11769937 TI - Differences of degree: representations of India in British medical topography, 1820-c. 1870. PMID- 11769938 TI - The debate about acclimatization in the Dutch East Indies (1840-1860). AB - Around the middle of the nineteenth century, conflicting views were put forward on the influence of climate on health and disease in the Dutch East Indies. In this part of the world, old Hippocratic ideas influenced views on the cause of disease much longer than in the Netherlands. Moreover, Brunonian theories--which had been discarded in the Netherlands--fitted the discussion about the effect of temperature on the body. Additionally, scientific medicine was introduced. Scientific methods, such as the collection of meteorological and statistical data, were promoted by a small group of military health officers. However, the use of scientific data did not guarantee a clear-cut opinion on the causes of disease. Numbers proved as disputable as other, less objective, medical observations. Mortality statistics and numbers of patients especially were used as arguments in various discussions. The example of Bosch, who changed his views on the dangers of tropical climate, demonstrates that statistics could be used for different purposes. At first, in his position as General Inspector, he used them as an argument to provide better care for the military personnel; later, when retired and a civilian, he used them as justification for colonization in relation to an intended improvement of the living conditions of the natives. The dangers of tropical climate for the health of Europeans were played down as soon as other--primarily economic--motives for living in the tropics became strong enough. PMID- 11769939 TI - Adolf Muhry (1810-1888): Gottingen's Humboldtian medical geographer. PMID- 11769940 TI - August Hirsch: as critic of, and contributor to, geographical medicine and medical geography. PMID- 11769941 TI - Effects of hostility and lifestyle on coronary heart disease among middle-aged urban Japanese. AB - OBJECTIVE: To explore the association between multi-dimensional aspects of hostility and coronary heart disease among middle-aged urban Japanese. SUBJECTS AND METHODS: We conducted a case-control study. Cases were consecutive patients with acute coronary syndrome admitted to a hospital in Japan. Fifty-three patients (45 men and 8 women) aged 35 to 65 were enrolled. For each case, two sex and age (+/-2 years) matched controls were recruited from among participants in a health check-up program at a health promotion center located in the same area as the hospital. Two questionnaires, both with four components, were used to measure hostility and coping with anger: the one was for anger, hostility, physical aggression and verbal aggression, and the other for aggression, social inhibition, guilt, and controlled affect. RESULTS: The scores of all components from two questionnaires were higher for cases than controls, but the differences were not significant. Multivariate analysis showed that anger, fat intake, alcohol consumption and house size were significantly associated with the etiology of acute coronary syndrome. CONCLUSION: Anger, lifestyle, and socioeconomic status play important roles for the etiology of coronary heart disease in middle-aged urban Japanese. PMID- 11769942 TI - Meta-analysis of multiple myeloma and benzene exposure. AB - Epidemiologic studies have suggested that benzene exposure may be a risk factor of multiple myeloma (MM). We performed meta-analyses of case-control studies to assess the association between occupational exposure to benzene and the risk of MM. We divided the occupational sources of benzene exposure into 4 categories, benzene and/or organic solvents, petroleum, petroleum products, and engine exhaust, for conducting the meta-analysis. As a result, a significant positive association was indicated between exposure to engine exhaust and MM (summary odds ratio or summary OR=1.34, 95% confidence interval or 95%CI=1.14-1.57). However, no significant associations were obtained for benzene and/or organic solvents (summary OR=0.74, 95%CI=0.60-0.90), petroleum (summary OR=1.11, 95%CI=0.96-1.28) and petroleum products (summary OR=1.08, 95%CI=0.89-1.33) with risk of MM. These results suggested that benzene exposure itself was not likely to be a risk factor of MM. It is thought that several harmful chemical agents in engine exhaust, other than benzene, could be etiologically related to the risk of MM. Further case-control studies on MM are needed to obtain more information about detailed occupational exposure to toxic substances. PMID- 11769943 TI - Measles epidemiology and outbreak investigation using IgM test in Laos. AB - Following the Pan American Health Organization (PAHO) recommendation on measles elimination, the Western Pacific Region of WHO (WPR) is emphasizing accelerated measles control programme especially since the achievement of polio eradication in WPR in 2000. This includes upgraded surveillance and mass measles vaccination campaign for children aged 9 months to 4 years. However, there are limited scientific evidences supporting the feasibility of this programme in Laos. To examine measles elimination feasibility in the country, we conducted measles outbreak investigation using immunoglobulin M (IgM). From March 1999 to March 2000, we conducted 7 outbreak investigations. At the outbreak sites, we examined clinical manifestations of cases and collected individual data. About five blood samples were drawn from each outbreak, and IgM antibodies to measles were tested. Of 7 investigated outbreaks, 5 were confirmed as measles, one was chickenpox, and one occurred in the inaccessible area due to flooding. In a village of high land Lao, blood drawn was refused. Of 185 cases, 64 (34.6%) cases were immunized, and 110 (59.5%) were unimunized. The estimated vaccine efficacy is 67.9%. The number of measles cases among school-aged children was 74 (40.0%), which represented 2.5% of the total population in investigated villages. Our findings showed various difficulties of the surveillance and the limited outcomes of mass measles vaccination campaign under the accelerated measles control programme by WPR. Efforts to improve cold chain as well as increasing routine immunization coverage must be the priority of measles control. PMID- 11769944 TI - Reference value of immunoglobulins in healthy school children of Bangladesh. AB - The reference value of immunoglobulins (Igs) should be known for a population concerned because it is influenced by many clinical and local conditions. As yet the reference value of the Igs have not been determined in Bangladeshi children. This study determined the reference value of Igs in apparently healthy 261 rural Bangladeshi primary school children (aged 5 to 14 years, mean 9.3 years). IgG, IgM and IgA were determined by an auto-analyzer. The mean (standard deviation) value of IgG was 1728 (344) mg/dl. The corresponding values for IgM and IgA were 200 (88) and 163 (63) mg/dl, respectively. The 95% reference value calculation in all subjects showed that the range for IgG was 1103 to 2524, IgM was 92 to 390, and IgA was 72 to 325 mg/dl. These values could be used to evaluate Ig status in children with a variety of clinical conditions. PMID- 11769945 TI - Development and validation of specific carotene food composition tables for use in nutritional epidemiologic studies for Japanese populations. AB - Assessment of dietary intake is important to understand the relationship between nutrition and health. Although the role of specific carotenoids has recently been of great interest, there are no comprehensive food composition tables for intake of specific carotenoids in Japan. We have therefore developed a new carotene food composition table that shows the alpha- and beta-carotene values based on an extensive review of the literature (FCT1). Using a 14- or 28-day diet record data of sample population (n=188), we selected 12 important foods to two carotene intakes. We analyzed the carotene contents of the foods, and developed the another composition table in which the food contents were replaced by the analytical values (FCT2). Carotene intakes of the population were significantly different between these two composition tables. However, the correlations between the dietary intake and the serum concentrations were almost identical, i.e., partial correlations using FCT1/FCT2 were 0.32/0.30 and 0.33/0.36 for alpha carotene and 0.28/0.28 and 0.30/0.29 for beta-carotene in men and women. The similar correlations with the serum concentrations may indicate an comparable value for ranking individuals between the two tables. However, the results were inconclusive for the estimation of absolute intakes. PMID- 11769946 TI - Problems in implication of epidemiology submitted as evidence to the court of air pollution health damages trials. AB - Civil lawsuits relating air pollution health effects presented often times in Japan. As a evidence of causal relation between air pollution exposure and respiratory diseases, epidemiological studies were submitted to the courts. An interpretation of these studies by judges were markedly different and unique from ordinal epidemiological understanding; scientific understanding of the studies. Based on these unique implication of the evidence, the judgment announced forcefully recognizing a existence of causal relationship between exposure to pollution and disease outcome. The author wishes to let epidemiologists know the details of this phenomena, hoping a correct usage of epidemiology in the course of deciding judgment at civil lawsuit. PMID- 11769947 TI - Lung cancer, myocardial infarction, and the Grossarth-Maticek personality types: a case-control study in Fukuoka, Japan. AB - Grossarth-Maticek and colleagues have shown, in their prospective studies, a strong relationship of their personality types, Types 1 and 2, to cancer and coronary heart disease (CHD), respectively. Relevant information is limited from replication studies, and little is known about psychosocial factors in relation to cancer or CHD in Japan. Subjects included 95 cases of lung cancer (LC), 94 cases of myocardial infarction (MI) and 596 controls. The controls were men and women who visited a clinic for a health checkup. The Grossarth-Maticek personality types, Types 1 to 6, were assessed using the Short Interpersonal Reactions Inventory. The distributions of the 6 personality types were compared between the case and control groups, adjusting for sex and age class. The relation of each of the 6 types to LC and MI were examined in terms of odds ratio, using a logistic regression model controlling for age, sex, job status, education level, and smoking status. As regards the distribution analysis, Types 1 and 2 in the LC and MI groups each were not more prevalent than the controls, respectively. High score of the Type 1 scale was associated with a statistically nonsignificant decrease in LC risk. MI risk was significantly, positively associated with the Type 2 and 5 scales, and unexpectedly, positively related to the Type 3 scale. The present findings partly supported the Grossarth-Maticek theory, but there remain some conflicting issues to be confirmed in future studies. PMID- 11769948 TI - Competency-based education: the new panacea? PMID- 11769949 TI - Faculty practice: how it enhances teaching. AB - This article is a presentation of the two authors' views on faculty practice and how both have operationalized the practice option. Both describe how the practice option has positively affected their teaching and their students' learning in a university baccalaureate nursing program located in the midwestern United States. The authors are full-time, master's prepared faculty members who have been in the faculty practice track for 2 years. Both teach in the junior year of a 4-year baccalaureate program. The first author (D.M.G.) is a staff nurse who works in a community hospital and serves on the hospital's clinical nursing research committee. The second author (C.R.S.) is a clinical research nurse coordinator who performs and manages pharmaceutical trials at multiple inpatient and outpatient locations. In this article, the authors examine faculty practice in general and the various models currently used. In addition, they explain their individual academic positions, the duties and responsibilities accompanying each of their practice roles, and the integration of those practice experiences into their clinical and classroom learning. PMID- 11769950 TI - Novice faculty: encountering expectations in academia. AB - New faculty rarely are prepared educationally or experientially for multiple roles and expectations. This phenomenological study was designed to uncover the meaning of the new faculty experience. A purposeful sample of nursing faculty, who were in their first year in a new position, were interviewed to gain an understanding of their experience. A hermeneutical method of data analysis revealed common meaning in the experience of new faculty. The focus of this article is on one theme--expectations--from the distinct perspective of the novice faculty participants. Novice faculty had expectations of what their new role would involve from their prior experience as students, and they perceived expectations of them by other faculty and students. With limited experience in academia, novice faculty described how they tried to put their own and others' expectations into perspective. The stories of these novice faculty reveal inadequacies in the ways new faculty are prepared and mentored. Implications arising from this study encourage revisiting the practices surrounding the preparation and retention of new nursing faculty. PMID- 11769951 TI - Student outcomes of the healing web: evaluation of a transformative model for nursing education. AB - The Healing Web is a transformative nursing model, bridging gaps between nursing education and practice, baccalaureate and associate degree education, and public and private educational institutions. It is an educational prototype in which nursing students experience collaborative clinical practice in a differentiated practice model. Based on the Healing Web framework, it was hypothesized that the educational partnership model would influence specific student competencies (i.e., caring abilities, leadership skills, assertiveness, and professional nursing behaviors). Students in the Healing Web program scored higher in caring knowing, caring courage, leadership, and assertiveness than their counterparts who participated in traditional clinical experiences. Students identified collaboration, partnership with students and staff, and learning to value different nursing roles as primary benefits of the experience. Findings support the contribution of Healing Web experiences to selected student outcomes, but the research is limited by instrumentation, small numbers, and the question of adequate "dosage." Future research will emphasize qualitative methods to explicate significant concepts more completely. PMID- 11769952 TI - Helping students use APA format. PMID- 11769953 TI - Teaching abstract concepts by metaphor. PMID- 11769954 TI - Playing jigsaw: a cooperative learning experience. PMID- 11769955 TI - Implications of chemically impaired students in clinical settings. PMID- 11769956 TI - The role of the biostatistician in cancer research. AB - This article considers triumphs and challenges for biostatisticians working in oncology at the beginning of the 21st century. The impact of three major articles in biostatistics in the 20th century is considered: Cornfield's 1951 paper on estimating comparative rates from clinical data; Mantel and Haenszel's 1959 paper on obtaining summary measures of relative risk, adjusting for stratification factors in epidemiological studies; and D. R. Cox's 1972 paper, which developed the proportional hazards model for evaluating the effect of covariates on survival time outcomes. Biostatistical challenges for the 21st century are considered for the areas of clinical trials, survival analysis, and statistical genetics. PMID- 11769957 TI - Minimally invasive surgery in breast cancer treatment. AB - As genetic and biological treatment modalities are developed that can be custom designed for individual patients, the possibility that breast cancer can be managed as a chronic long-term disease becomes more real, and the requirement for minimally invasive surgical intervention used as part of a multidisciplinary treatment approach becomes more pressing. Rather than fearing that they will be replaced, surgeons should enthusiastically move into this dynamic phase in the development of new surgical techniques for the treatment of breast cancer. This article will discuss such techniques in three evolving areas: 1) management of the axilla after neoadjuvant chemotherapy; 2) sentinel node dissection; and 3) radiofrequency ablation of primary tumors of the breast. PMID- 11769958 TI - Radiation therapy for malignant lymphoma: enduring importance in the era of systemic therapy. PMID- 11769959 TI - Post-mastectomy irradiation: the continuing controversy. PMID- 11769960 TI - Progress in CLL, chemotherapy, antibodies and transplantation. AB - Over the last decade, major advancements in our understanding of chronic lymphocytic leukemia (CLL) and its variants have occurred. It has become apparent that there is diversity in types of CLL including those patients that do or do not have hyper-mutation of their immunoglobulin genes. Mutated genes confer a favorable prognosis. One of the major advances in our therapy has been the discovery of the activity of purine analogs, which have been demonstrated to be more active than conventional therapy in achieving complete remission, prolonged remission duration, and a suggestion of improved survival. More recently, based on information that purine analogs inhibit DNA repair, rational combinations have been developed. In particular, fludarabine plus cyclophosphamide appeared to have added activity compared to either drug given alone or in sequence. This has led to a higher response rate, longer time to progression, and an improvement in survival in patients treated following prior alkylating agents. Two monoclonal antibodies, Rituximab and Campath-1H, have become available for clinical use and research. Rituximab has modest activity as a single agent, with higher response rates being noted in patients who receive more intensive regimens. Rituximab has been successfully combined with chemotherapy, and in association with fludarabine plus cyclophosphamide (FCR) has a very high response rate and the ability to obtain polymerase chain reaction (PCR) negativity for the immunoglobulin heavy chain region. Campath-1H is very active as a single agent and is being recommended for treatment for patients with fludarabine refractory disease and will receive increased attention as a research agent in earlier-stage patients. Autologous and allogeneic bone marrow transplantation have emerged as significant treatments in CLL. The ability to achieve responses in bone marrow and peripheral blood with newer regimens has given the opportunity to collect stem cells from patients. There is a suggestion that intensification of remissions with autologous transplant can lead to PCR negativity and prolonged remissions. Allogeneic transplantation has been demonstrated to be effective with a strong suggestion of graph versus leukemia effect. This has been utilized in the development of non-ablative marrow allogenaic bone marrow transplant programs. Non-ablative transplants appear to be as effective as ablative transplants in the most recent analysis. Thus, multiple modalities have been brought together to achieve high-quality complete remissions in CLL, giving the prospect of improved survival. PMID- 11769961 TI - ST1571: a paradigm for clinical trials of molecularly targeted agents. PMID- 11769962 TI - The roles of adoptive and active forms of immunotherapy in the cure of children suffering from acute lymphoid leukemia: a) underestimation of active immunotherapy benefit, b) its immunogenetic indications to select sensitive patients, hence prevent chemotherapy's late effects. AB - Children's acute lymphoid leukemia (ALL) chemotherapy started in 1948 with antimetabolites combined with steroids. It was enriched in 1959 with vincristine and cyclophosphamide and, in 1970, with daunomycin. It induced more and more apparently what were called complete remissions, and prolonged more and more the survivals without reducing however, until 1973, the (100%) mortality. It started to reduce it at the fifth year, to 20 and even 40% between 1973 and 1976, due to progressive and maximal intensification and duration of chemotherapy. It is in the same period that we proposed to apply in ALL remissions after relapses and in the first remissions of the most malignant type, allogeneic bone marrow grafts; we published the first success in human ALL in 1963, and clinically observed the same actions as those described experimentally: cytoablation of both leukemia and hematopoiesis, the latter being restored by the graft, whose reaction versus the residual neoplastic cells (called graft versus leukemia or GvL) appeared to be able to often eradicate them, at the cost however of a graft-versus-host reaction (both reactions sharing the same mechanism). One of us became a member of the Committee of the International Bone Marrow Transplant Registry, whose results showed the improvement in the prognosis of the aggressive form of ALL. The intensity and length established for chemotherapy for the most severe form of children's ALL have often been applied to the intermediary and to the least aggressive ones. The global 5-year survival increased to 60% between 1976 and 1984, and is around 80% today. But the registration of late debilitating or malignant effects of chemotherapy toxicities makes us wonder if some patients have not received an excessively intense and long application of cytostatics (often combined with ionizing radiations on CNS). In fact, the patients belonging to some HLA phenotypes (A33 and B17) have appeared to be especially often cured with active immunotherapy (killed leukemic cells and/or BCG), whose action was shown by specific cytotoxicity amplification, which was applied after short adjuvant chemotherapy, and hence is able to reduce the long chemotherapy incidence of debilitating or malignant late effects. Sakurai's group confirmed our absence of late relapses after ALL active immunotherapy, which contrasts with their risk after maintenance chemotherapy, whose minimal residual disease is a worrisome stumbling block to the cure. PMID- 11769963 TI - Cytokine deregulation in cancer. AB - Endogenous cytokines are aberrantly produced in many cancers, and serve as autocrine growth factors or indicators in immune response to the tumors. Hence, cytokine deregulation is likely to participate in the development or evolution of the malignant process. Over the last few years, endogenous cytokine levels have been correlated with phenotypic manifestations of cancer and with prognosis. For instance, serum IL-6 levels are elevated in both relapsed and newly-diagnosed Hodgkin's and non-Hodgkin's lymphoma, and these levels correlate with established prognostic features. Furthermore, in diffuse large cell lymphoma, serum IL-6 level is an independent prognostic variable for both complete remission and failure-free survival. Serum IL-10 levels are also elevated in lymphoid malignancies and predict outcome. In some cases, it may be that the balance between endogenous cytokine agonists and antagonists is disrupted. For instance, in chronic myelogenous leukemia, high cellular (leukocyte) levels of IL-1 beta and low levels of IL-1 receptor antagonist (IL-1RA) are seen in advanced disease and correlate with reduced survival. The molecular mechanisms underlying cytokine deregulation are now being investigated, with preliminary data suggesting heterogeneous genetic driving forces, including oncogene aberrations and viral infection. PMID- 11769964 TI - Myeloma: what have we learned? PMID- 11769965 TI - Recent advances in treatment of multiple myeloma and Waldenstrom's macroglobulinemia. PMID- 11769966 TI - New biology and therapies in soft tissue sarcomas. PMID- 11769967 TI - Breast cancer chemoprevention: current clinical practice and future direction. AB - With the unblinding of the Breast Cancer Prevention Trial (BCPT) in 1998, the clinical management of breast cancer prevention patients has expanded from the time-honored triad of breast cancer screening to include breast cancer risk assessment and risk reduction. With a proven 49% reduction in the incidence of breast cancer, tamoxifen is now the gold standard in chemoprevention for breast cancer risk reduction for women at increased risk of the disease. The suggested 74% reduction in the incidence of breast cancer seen with raloxifene in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial is the basis of the now ongoing Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer. Findings are anticipated in 2006. PMID- 11769968 TI - Translational research--traffic on the bridge. PMID- 11769969 TI - Clinical research today and tomorrow. PMID- 11769970 TI - Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. AB - The efficacy of osteogenic protein-1 (OP-1; BMP-7) in regeneration of articular cartilage was examined by creating knee chondral defects in sheep. With a specially designed instrument in both knees, two 10 mm (diameter) chondral defects were created: one in the trochlea and the other on the femoral condyle. The recombinant BMP was delivered via an extra-articulary positioned mini-osmotic pump, which was fixed to the femoral diaphysis above the knee joint, and connected by a polyethylene tubing to the articular space. Prior to use, the compatibility of OP-1 with mini-osmotic pumps was tested in vitro by measuring aggregation/precipitation and modification of the released protein by size exclusion and reversed phase HPLC. The average amount of aggregation was 15% and about 5% of OP-1 was modified. However, the biological activity of OP-1 released from pumps over a period of 2 weeks at 37 degrees C was equal to ROS cell assay OP-1 standard. Following surgery, a total of 55 microg (low dose) or 170 microg (high dose) OP-1 in acetate buffer (pH 4.5) was slowly released from the pump over a period of 2 weeks. The pumps connected to control knees were filled with acetate buffer as a vehicle. Twelve animals were operated, six of which were treated with the low OP-1 dose, and six with the high OP-1 dose. Three sheep of each group were killed either at 3 or 6 months following surgery, based on arthroscopical evaluation. The chondral defects in the control knees remained empty during the observation period. At 3 months following surgery, defects treated with both OP-1 doses were filled with connective tissue and cartilage. At 6 months following surgery, both doses of OP-1 stimulated regeneration in treated knees. The boundaries between new and old cartilage were well fused and mechanically resisted animals' weight bearing. The regenerated cartilage was rich in proteoglycans and type II collagen, as demonstrated by toluidine blue staining and immunohistochemistry. No signs of endochondral bone formation above the bony tidemark were observed. We suggest that a recombinant bone morphogenctic protein stimulates ingrowth of mesenchymal cells into the chondral defects which then transform into newly formed articular cartilage-like tissue. PMID- 11769971 TI - A growth and differentiation factor-5 (GDF-5)-coated suture stimulates tendon healing in an Achilles tendon model in rats. AB - Growth and differentiation factor-5 (GDF-5) is essential for normal skeletal development and induces tendon-and ligament-like structures at ectopic sites. Therefore, we investigated the influence of a GDF-5-coated suture on the healing Achilles tendon in rats. The right Achilles tendon in 80 rats was transected and sutured with an absorbable polyglactin suture. Animals were randomized to an uncoated-suture control and a GDF-5-coated suture group. At 1, 2, 4 and 8 weeks after surgery the repair tissue was evaluated biomechanically and histologically. Biomechanical testing revealed significantly thicker tendons, which were stiffer at 1, 2, and 4 weeks, in the experimental group than in the control group. The maximum tensile strength was significantly increased at 2 weeks after surgery. Histologically we found cartilage-like cell nests 4 weeks after tendon repair, which were positive for type II collagen. In conclusion, local growth factor delivery by a coated suture material showed a promising beneficial effect on tendon repair. The appearance of cartilage-like structures may demonstrate the chondroinductive capacity of GDF-5, which in these circumstances, however, might be overcome by modifications of the GDF-5 dose and/or the suture material. PMID- 11769972 TI - Site-directed mutagenesis of heparin-binding EGF-like growth factor (HB-EGF): analysis of O-glycosylation sites and properties. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a 22 kDa, O-glycosylated protein. HeLa cells infected with a recombinant vaccinia virus expressing human HB-EGF produced a secreted, bioactive protein, with Mr 22,000 that was decreased to 14,000 by treatment with O-glycanase. Site-directed mutagenesis of HB-EGF cDNA using oligonucleotide- and PCR-directed techniques was performed to change the potential glycosylation sites, Thr75 and Thr85, to alanine residues to prevent O-glycosylation. Purification and characterization of the mutant proteins demonstrated that: (i) both O-glycosylation sites of HB-EGF are utilized, (ii) HB-EGF secretion does not require O-glycosylation, (iii) removal of O-glycans does not affect proteolytic cleavage of the HB-EGF precursor, nor does it influence HB-EGF intracellular trafficking or subcellular localization, and (iv) HB-EGF produced by HeLa cells is heavily sialylated. Comparisons between glycosylation mutants and wild-type HB-EGF revealed no significant apparent differences in receptor binding activity. PMID- 11769973 TI - Transforming growth factor-beta1 supports the rapid morphogenesis of heterotopic endochondral bone initiated by human osteogenic protein-1 via the synergistic upregulation of molecular markers. AB - Members of the transforming growth factor-beta (TGF-beta) superfamily of proteins, the bone morphogenetic proteins (BMPs) and the TGF-beta isoforms, are involved in the coordination of cartilage and bone differentiation both in embryonic development and in postnatal life. Both osteogenic protein-1 (OP-1) and TGF-beta1 have been shown to be potent regulators and inducers of heterotopic endochondral bone induction in non-human primates. In marked contrast, TGF-beta1 does not induce heterotopic endochondral bone in rodents. In the primate, the osteogenic properties of OP-1 are synergistically enhanced by the combined administration of TGF-beta1. The binary application of OP-1 (0.1, 0.3, 1.0 and 3.0 microg) and TGF-beta1 (0.01, 0.03 and 0.1 microg) to 25 mg of guanidinium inactivated insoluble collagenous bone matrix as carrier in the rodent heterotopic bioassay for 7, 12 and 21 days resulted in a classical synergistic, dose-dependent and temporal up-regulation of OP-1-induced endochondral bone formation. There were significant increases in alkaline phosphatase activity (day 12) and calcium content (days 12 and 21). mRNA expression of OP-1, TGF-beta1, BMP 3 and collagens type II and IV, markers of bone formation, showed an up regulation of the genes (days 12 and 21) by the binary applications of the morphogens. Histologically, single applications of OP-1 elicited a dose dependent induction of endochondral bone formation while the binary applications resulted in a temporal acceleration of the morphogenetic cascade. The optimal ratio of OP 1/TGF-beta1 was 30:1 by weight for endochondral bone formation and expression of molecular markers. The present data provides insights to the mechanisms of synergistic molecular therapeutics for endochondral bone formation in clinical contexts. PMID- 11769975 TI - On the need for bigger and better think tanks. PMID- 11769974 TI - Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system. AB - The activation of hepatic stellate cells (HSC) during liver fibrogenesis has been shown to be mediated by paracrine and autocrine loops involving transforming growth factor-beta1 (TGF-beta1) as the main fibrogenic mediator secreted by activated macrophages, endothelial cells and liberated by disintegrated platelets. The cell-associated plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We have studied whether TGF-beta1 could modulate the plasminogen activation system in human HSC and the role of such protease system in the activity of TGF-beta1 on HSC. Urokinase plasminogen activator receptors (u-PAR), u-PA and plasminogen activator inhibitor type 1 (PAI-1) were determined by immunoassay and RNase protection assay. Cell migration, evaluated either as chemotaxis or as chemoinvasion, was studied in Boyden chambers after addition of TGF-beta1, and inhibition with anti-u-PA and anti-u-PAR antagonists [antibodies against u-PA and u-PAR and antisense oligonucleotides (aODN) against u-PAR mRNA]. We have shown that TGF-beta1 is not mitogenic for HSC, while it is a powerful motogen either in chemotaxis or chemoinvasion assays. TGF-beta1 up-regulates the synthesis and expression of PAI 1, as well as u-PAR expression and exposure at the cell membrane, while it does not affect u-PA levels. TGF-beta1-dependent chemoinvasion of reconstituted basement membrane exploits the cell-associated plasminogen activation system, since it is blocked by monoclonal antibodies against u-PA and against various u PAR domains, as well as by anti-u-PAR aODN. We have also observed a cumulative effect of TGF-beta1, b-FGF and PDGF in the invasion assay of HSC: in the presence of low amounts of TGF-beta1 the chemoinvasive activity of PDGF and bFGF is dramatically increased. Also this cooperation requires u-PAR and is inhibited by monoclonal antibodies against u-PAR domains I, II and III. PMID- 11769976 TI - The leisure satisfaction of people with psychiatric disabilities. AB - Leisure is considered to be an important part of life for every individual. This is even more so for people who have limited employment prospects and life options. The primary handicaps associated with mental illness create problems with social relationships and can hinder individuals from participating in or enjoying leisure pursuits. The aim of this exploratory study was to examine leisure satisfaction in a sample of one hundred adults with a mental illness who were clients of an Australian community mental health rehabilitation service. The Leisure Satisfaction Survey and the Life Skills Profile were administered to these clients to determine their leisure satisfaction and general functioning. Contrary to expectations, results indicated that the clients of mental health rehabilitation services believe that their leisure pursuits provide them with intellectual stimulation, enjoyable relationships with others and relaxation, suggesting that they are very satisfied with the activities they engage in during their leisure time. In general, these clients were more satisfied with their leisure than the normative population. Consistent with expectations, clients with lower disability and in particular with high capacity for social contact were most satisfied with their leisure pursuits. The significance of these results and the utility of the Leisure Satisfaction Survey with this population are discussed. PMID- 11769977 TI - Life circumstances of mothers with serious mental illnesses. AB - Individuals with a severe mental illness now have greater opportunities to pursue normal adult roles, including parenting. The research reported involved 379 women carrying out parenting responsibilities, recruited from the public mental health system in an urban area. The sample displayed great heterogeneity in educational levels, number of children, number of fathers for their children, and family living arrangements, except that most women were very poor. These women faced many significant stresses: living alone with their children, significant child behavior problems, and financial worries. Still, most of the women endorsed the significance of motherhood in their lives. Inattention by most mental health providers to parenting issues leaves many important needs unmet and is likely to have adverse consequences for these women and their children. Implications for psychosocial rehabilitation practice are discussed. PMID- 11769978 TI - Implementation of a computer assisted treatment planning and outcome evaluation system in a forensic psychiatric hospital. AB - This article describes the implementation of a computer assisted treatment planning and outcome evaluation process in a forensic psychiatric state hospital with a census of approximately 1000 patients. This process utilizes standardized assessment measures of patient functioning and facilitates the assignment of treatment activities that are explicitly related to assessed deficits. Beyond individual patient treatment planning, data generated in the course of computer assisted treatment planning are used in conjunction with other sources of datafor outcome evaluation and program development. PMID- 11769979 TI - Peer support: a theoretical perspective. AB - This article offers one theoretical perspective of peer support and attempts to define the elements that, when reinforced through education and training, provide a new cultural context for healing and recovery. Persons labeled with psychiatric disability have become victims of social and cultural ostracism and consequently have developed a sense of self that reinforces the "patient" identity. Enabling members of peer support to understand the nature and impact of these cultural forces leads individuals and peer communities toward a capacity for personal, relational, and social change. It is our hope that consumers from all different types of programs (e.g. drop-in, social clubs, advocacy, support, outreach, respite), traditional providers, and policy makers will find this article helpful in stimulating dialogue about the role of peer programs in the development of a recovery based system. PMID- 11769981 TI - Moving out and moving on: some ethnographic observations of deinstitutionalization in an Australian community. AB - Since the 1950s deinstitutionalization has taken place for people with mental illnesses in the Western world. The growth of community care and residential facilities, as well as planning and implementation of policies, has varied in timing and orientation. An appreciation of the process of change affecting people discharged to the community highlights their strength, resilience, and vulnerabilities. This paper outlines a two and a half year ethnographic qualitative study undertaken in Australia, where 47 long-stay psychiatric inpatients were discharged to the community. The process accompanied the amalgamation of two major psychiatric hospitals, resulting in the closure of one. Findings demonstrated slow but positive change for residents as they reintegrated into the community. A separate quantitative and economic study was undertaken alongside the qualitative study (for results see Hobbs, et al., 2000; Newton, et al, 2000; Lapsley, et al., 2000). PMID- 11769980 TI - Conducting focus groups with women with severe psychiatric disabilities: a methodological overview. AB - This article presents information on the methodology used in conducting focus groups with women with severe psychiatric disabilities. The purpose of the focus groups was to understand the experiences of low-income women with severe psychiatric disabilities in accessing and using primary health care services. Discussed are the design decisions researchers should reflect on when constructing and conducting focus groups with women with severe psychiatric disabilities. Information on how guidelines from the literature on conducting focus groups were adapted for these women as well as lessons learned from this experience are presented. PMID- 11769982 TI - Homeless mothers with severe mental illnesses and their children: predictors of family reunification. AB - Although many homeless women lose physical custody of children, prior studies have not examined predictors of reunification. To explore factors associated with separation and potential resources for reunification, baseline data from 1,542 homeless women with mental illness were used to identify unique characteristics of separated mothers. Separated mothers demonstrated greater vulnerabilities than accompanied mothers did, but more resources than women who are not mothers did. Of 698 separated mothers, 118 (17%) were reunited with children at 12 months. Changes in housing, psychosis, substance use and therapeutic relationships predicted reunification. Results suggest that programs for homeless mothers with severe mental illness can affect changes that promote family reunification. PMID- 11769983 TI - Peer education and advocacy through recreation and leadership. AB - Peer Education and Advocacy through Recreation and Leadership (PEARL) is an intervention based on principles of peer helping and psychosocial rehabilitation. Trained peers working as recreation advocates provided support to peers in psychosocial rehabilitation settings. Advocates promoted peer involvement in recreation and community activities as a strategy to enhance social support, independence, community inclusion, and quality of life. Evaluation findings indicate positive impacts on quality of life, empowerment, employment and educational preparedness among advocates. Outcomes of the PEARL project included developing a peer training curriculum, expanded leadership roles for participants, and improved quality of recreation services available within psychosocial rehabilitation programs. PMID- 11769984 TI - Improving accessibility: the experience of a Canadian Mental Health Agency. AB - This article describes the process undertaken by a community mental health organization in Toronto, whose staff are predominantly white and unilingual, to be more accessible and responsive to Toronto's diverse ethnic communities. Board, staff, and consumer input provided guidance for the development of antidiscrimination and antiracism policies, and subsequently for expectations that each program find ways to implement these policies. The article focuses on events and opportunities of one of the programs that led to connections being established between the organization and the Somali community. PMID- 11769985 TI - Impact of behavioral knowledge on job stress and the perception of system impediments to behavioral care. PMID- 11769986 TI - Consumer experience with payeeship provided by a community mental health center. AB - We surveyed 28 participants in a program in which the clinical therapist and money manager were different staff members. Patients reported strong therapeutic alliances with both the money manager and treating therapist as assessed by the Working Alliance Inventory. Alliance scores for the two providers were highly correlated (p = .68) and not significantly different from each other. Most patients endorsed overall satisfaction with the money management service, and report program-related benefits in housing, achieving abstinence, avoiding financial predators and budgeting arrangements. A significant minority endorsed some feeling of coercion, and coercion was associated with a weaker therapeutic alliance. PMID- 11769987 TI - Marriage and mental illness. AB - I have not read anything regarding persons who marry while living with serious, persistent mental illness. I married in the 1960s when persistent mental illness was considered a "nervous breakdown" and not an ongoing disease. With this article, I want to educate and explore thought in other persons who might share the same problems I experienced. I want to give a voice to the isolation I felt while married, coping with my illness. I felt so different from other married women with my closeted illness. I have two beautiful daughters who suffered a tragedy in their young lives when I became ill, yet our love seems to have survived and our relationship each day grows. With this article I want to give a voice to one marriage and mental illness. I want someone who reads this to say, "Yes, I feel like that; I know I'm not alone." PMID- 11769988 TI - The real schizophrenia, an abstract life. PMID- 11769989 TI - Post-thyroidectomy superior laryngeal nerve injury. AB - Voice dysfunction after thyroidectomy may be caused by damage to laryngeal nerves or lesions to strap muscles with laryngo-tracheal movement impairment. Injury to an external branch of the superior laryngeal nerve (EBSLN) is sometimes difficult to recognize clinically and its electromyographic incidence ranges from 0% to 58%. In this study we evaluated, 12-18 months postoperatively, 45 patients who had undergone thyroid surgery (6 total lobectomy, 5 subtotal thyroidectomy, and 34 total thyroidectomy), using a subjective interview, laryngeal videostroboscopy and spectrographic analysis with a multidimensional voice program. Vocal parameters included fundamental frequency, jitter, shimmer, noise-to-harmonic ratio (NHR) and degree of sub-harmonics. Laryngeal electromyography (LEMG) of the cricothyroid (CT) muscles was performed in 21 subjects with voice problems (35 EBSLNs) using a modified method for the CT recording. In 3 patients of this group (14%) LEMG documented a unilateral EBSLN injury. Easy voice fatigue and decreased pitch range were the most common symptoms after surgery. Average values of vocal parameters pre- and postoperatively in patients without neural damage (n = 42) were: jitter 0.64% and 0.78%, shimmer 3.25% and 3.54%, and NHR 0.12% and 0.13%, respectively (P > 0.05). Acoustic analysis revealed altered patterns in some patients with no objective evidence of damage to EBSLNs, suggesting an extralaryngeal cause of vocal dysfunction, such as laryngo-tracheal fixation or lesions to strap muscles. We conclude that laryngeal videostroboscopy and spectrographic analysis are very useful to assess voice problems after thyroidectomy, including in patients without LEMG-proven neural lesions, in order to suggest early speech rehabilitation, especially in professional voice users. PMID- 11769990 TI - Leeches in the larynx. AB - This is a report of four patients who inhaled leeches. They presented with severe attacks of inspiratory stridor, difficulty in breathing and spitting blood. Indirect laryngoscopy revealed a dark greenish living foreign body in the larynx in each case. Laryngoscopy was performed with local anaesthesia in two of the cases and general anaesthesia was used in the other two. The leeches were removed with forceps. PMID- 11769991 TI - Retropharyngeal lipoma causing dysphagia. AB - Lipomas of the retropharyngeal region are rare, slow-growing tumours that attain a large size before producing symptoms such as dysphagia and dyspnoea. Clinical diagnosis may be difficult. However computed tomography or magnetic resonance imaging is the investigation of choice and helps in definitive diagnosis preoperatively, although final histological confirmation is essential. Surgery is the treatment of choice. In the following paper we report a case of retropharyngeal lipoma presenting with dysphagia which was managed surgically with complete amelioration of symptoms. PMID- 11769992 TI - Recurrent laryngeal nerve palsy after thyroid cancer surgery: a laryngological and surgical problem. AB - Recurrent laryngeal nerve paralysis is one of the most frequent complications after thyroid surgery due to goiter and cancers. A higher probability of this complication occurs after secondary procedure of the thyroid and in malignant cases. The symptoms may differ and depend on many factors. Generally, patients need careful ENT and surgical care including diagnosis and treatment. Four hundred and sixty-six patients who underwent thyroid operation due to cancer were analyzed. The group was composed of 227 papillary carcinoma, 87 follicular carcinoma, 51 medullary carcinoma, and 101 anaplastic carcinoma. Two hundred and fifty-three total thyroidectomies, 82 lobectomies and subtotal second lobe operations, 91 subtotal thyroidectomies, and 40 biopsies (wedge resections) were performed. In all 426 total and subtotal thyroidectomies an attempt to identify the recurrent laryngeal nerves was carried out. For 360 patients (77%) the surgical procedure was primary and for 106 patients (23%) the operation was secondary. Preoperative and postoperative laryngoscopic examinations were performed in all patients. Every patient with palsy underwent special laryngological procedures if needed (tracheotomy, phoniatric rehabilitation, conservative treatment and surgery in lack of improvement). The rate of postoperative vocal cord paralysis was 4.7%. The permanent palsy rate was 3.5%. In 1.2% recovery was observed. Of the 4.7% palsy rate, 3.2% concerned unilateral palsy and 1.5% bilateral pathology. Using the chi2 test, no significant differences between the rate of unilateral and bilateral paralysis and between temporary and permanent paralysis were found. On the basis of our material and results, identification the recurrent laryngeal nerves should be mandatory at surgery, thereby avoiding paralysis. Special laryngological procedures and surgical care from the beginning of paralysis are necessary for patients with vocal cord palsy. It allows to diagnose and treat patients with quite good results. PMID- 11769993 TI - Surgical voice restoration after total laryngectomy: long-term results. AB - Tracheoesophageal puncture (TEP) with a voice prosthesis has been the preferred treatment for speech rehabilitation of total laryngectomies at the Dr. Peset Hospital since 1984. This study reviews 350 consecutive patients over a 15-year period. There were 334 patients with primary and 16 with secondary TEP. Long-term tracheoesophageal speech was achieved in approximately 70% of our patients. Problems related to or affecting TEP for voice restoration were studied. The different types of problems identified occurred in proportions ranging from 0.6% to 18%. Most of them were easily managed, but problems such as salivary leakage and dislodging of the prosthesis led to tracheoesophageal tract closure in 30% of the patients. PMID- 11769994 TI - Vestibular schwannoma: negative growth and audiovestibular features. AB - At the University Medical Center Utrecht, non-operative management was used for 44 patients with a unilateral vestibular schwannoma between 1990 and 1997. During that period, consecutive tumor sizes were determined by magnetic resonance imaging. Three of the 44 patients showed an average decrease in tumor size of 16.7% according to American Academy of Otolaryngology-Head and Neck Surgery standards. This study describes the initial vestibular status and audiometric changes measured over up to 10 years in these three patients. Vestibular function was determined once, by means of the bithermal caloric test, the torsion test, the saccade test, the smooth pursuit test, and the registration of spontaneous nystagmus. The three patients had severe vestibular paresis on the affected side. Pure-tone and speech audiometry were performed at regular intervals. Although the size of their tumors decreased, their hearing gradually deteriorated, just as it does in the majority of patients with a growing or stable vestibular schwannoma. The observations presented here suggest that the development of symptoms in a vestibular schwannoma does not differentiate between patients with a stable, growing or shrinking tumor. The development of symptoms may be the result of the same pathogenetic mechanism. PMID- 11769995 TI - Up-regulation of matrix metalloprotease-9 in middle ear cholesteatoma- correlations with growth factor expression in vivo? AB - The role of matrix metalloproteases and their regulation in the pathology of middle ear cholesteatoma is still unclear. Recently we have demonstrated that incubation of keratinocytes with cholesteatoma debris and granulation tissue extracts causes induction of gelatinase B (matrix metalloproteinase-9, MMP-9) secretion in vitro. Antibodies against a variety of growth factors revealed some inhibitory effect on MMP-9 induction, caused by debris or granulation tissue extracts. In order to investigate the coherence of growth factor expression and matrix metalloproteinase activity in vivo in middle ear cholesteatoma, we performed quantitative gelatin zymographic analysis with tissue homogenates of 37 cholesteatoma and nine external ear canal skin (EACS) samples. Furthermore we quantified levels of the cytokines IL-1alpha, IL-1beta, TNF-alpha, TGF-beta and EGF present in tissue extracts, using enzyme-linked immunosorbent assays (ELISA), and correlated cytokine concentrations with gelatinolytic activities. Zymographic analysis revealed a highly heterogeneous expression of gelatinase A and B in cholesteatoma specimens. As shown previously, MMP-9, but not MMP-2, was increased in cholesteatoma when compared to EACS samples. ELISA studies revealed a significantly elevated IL-1alpha level in cholesteatoma. Regression analysis involving gelatinolytic activity and cytokine concentrations in tissue homogenates showed no statistically significant correlation between expression of gelatinases and the cytokines IL1-alpha, IL1-beta, TNF-alpha, TGF-beta or EGF. The discrepancy between in vitro observations and the situation in vivo is discussed critically. PMID- 11769996 TI - Steroids, carbogen or placebo for sudden hearing loss: a prospective double-blind study. AB - There is no consensus regarding treatment modalities for idiopathic sudden sensorineural hearing loss (SNHL). In order to evaluate the effectiveness of steroid or carbogen inhalation therapies, a prospective double-blind placebo controlled study was designed. All 41 patients enrolled in the study had unilateral SNHL with no prior history of SNHL, otological pathological history or otoscopic findings. Patients were assigned to four treatment groups: prednisone tablets, placebo tablets, carbogen inhalation or room air inhalation. All were treated for 5 days. The audiometric data at admission was compared to that at day 6 and to data collected at follow-up (average 33 days). Results revealed no significant difference between the groups for early or late audiometric outcome. Age, time from onset of symptoms to initiation of treatment, tinnitus, audiogram configuration, and the presence of vertigo at onset did not significantly affect the outcome. The discrimination scores that were poor in all patient groups on admission improved within days in all groups. These findings suggest that steroids or carbogen inhalation have no therapeutic advantage over placebo. Also, regardless of treatment modality, hearing continued to improve for at least a month after treatment was stopped. PMID- 11769997 TI - Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: new trends in pathophysiology, prevention and treatment. AB - Mucositis is the intensity-limiting toxicity in the management of locally advanced non-resectable head and neck cancer with radiotherapy and chemotherapy. New radiation modalities (hyperfractionation and/or acceleration) as well as combined modality regimens in this situation induce higher rates of acute toxicity. Hyperfractionation, for example, allows higher control rates, with few late toxicities, but it slightly increases acute mucositis. The addition of chemotherapy introduces systemic toxicity and can exacerbate local tissue reactions when used concurrently with radiotherapy. Mucositis is recognized as the principal limiting factor to further treatment intensification. As local regional control and overall survival are related to dose-intensity in this case, further research into the assessment, analysis, prevention and treatment of mucosal toxicity is not only crucial to improvement in quality of life, but certainly also to improved rates of disease control. Several topical and systemic treatments are directed to the decrease and the acceptance of this acute toxicity, but few have shown a significant preventive effect. The efficacy of low level laser therapy in the management of such toxicity could hence yield important developments with this method in the field of oncology. PMID- 11769998 TI - Near total laryngectomy with epiglottic reconstruction. our experience of 65 cases. AB - From 1980 to 1998, 65 patients whose glottic lesions were classified T1 or T2 were operated with a reconstructive anterior frontal laryngectomy with epiglottoplasty such as described by Tucker (Arch Otolaryngol Head Neck Surg 115:1341-1344). This procedure consists of resection of the two vocal cords, in some cases one arytenoid, the anterior commissure with a part of the thyroid cartilage, the anterior part of both false vocal cords, and of 1 cm of the subglottis. The epiglottis is grasped downward to close the larynx. There were no per or postoperative deaths. Our functional results confirm those reported in the previous publications. The mean time of removal of the nasogastric tube was about 12 days and the patients were generally satisfied about their residual voice. Decannulation was performed after satisfactory peroral feeding, generally about 2 weeks postoperatively. Three patients only required subsequent procedures which can be considered due to functional failures. There were four recurrences, which means a 5-year actuarial local control rate of 94%. This operation takes place as part of our surgical treatment policy of laryngeal carcinomas, considering that this surgery is like an extensive frontolateral laryngectomy. In case of an infiltrating tumor or in case of invasion to the arytenoid cartilage, we perform a supracricoid partial laryngectomy with crico-hyoido-epiglottopexy (the Majer Piquet's procedure). PMID- 11769999 TI - Evaluation of clinical parameters in patients with obstructive sleep apnea and possible correlation with the severity of the disease. AB - Obstructive sleep apnea (OSA) is a complex disease whose etiology is multifactorial and incompletely understood. This article focuses on upper airway anatomy evaluation and the standardization of different physical findings in patients with OSA and on the possible correlation of these physical findings with the severity of the disease. All patients underwent a physical examination and polysomnography. The physical examination included tonsil size, modified Mallampati grade, neck circumference, lateral clinical craniofacial assessment and body mass index (BMI). The study group consisted of 85 patients. A statistically significant correlation between tonsil size and BMI and with the respiratory disturbance index (RDI) was detected (P = 0.004 and 0.03 respectively). Also patients with a craniofacial anomaly have a higher RDI level than the patients without this anomaly (P = 0.03). This study has identified some standardized physical findings for predicting the severity of OSA. We aim to benefit from these findings in the selection of a rational treatment modality selection for patients with OSA. PMID- 11770000 TI - SPET monitoring of auditory cortex activation by electric stimulation in a patient with auditory brainstem implant. AB - Auditory cortex activation following multifrequency acoustic stimulation has been evaluated by means of single photon emission tomography (SPET) in one patient before and after an auditory brainstem implant (ABI). No activation could be observed after acoustic stimulation before ABI. After ABI stimulation in the coronal and axial slices, the activation within the temporal cortex contralateral to the stimulated ear was twice (43.76%) that of normal controls (23.94 +/- 2.74%). This marked difference was not present in other selected cortical auditory areas (homolateral temporal, homolateral and contralateral parietal cortices). The temporal cortex was also examined with six consecutive sagittal slices from 18.75 mm up to 56.25 mm lateral to the midline. A very strong activation (51.20%) compared with that of normal controls (9.94 +/- 7.45%) was detected in the 25.26-mm sagittal slice of the temporal cortex contralateral to the stimulated side. The remaining sagittal slices showed an almost normal post stimulatory activation. As the 25.26-mm sagittal slice corresponds to the medial part of the auditory temporal cortex, its activation suggests that electrode stimulation is concentrated on the region of the cochlear nucleus in which the neurons that transduce high frequencies are located. SPET can be considered useful, in combination with electric auditory-evoked potentials, to obtain information on ABI placement and function, effectiveness of acoustic stimulation, degree of cortical stimulation and tonotopic spatial distribution of auditory cortex activation. PMID- 11770001 TI - Effects of perineural application of glycerol on the facial nerve: an experimental study. AB - Current procedures for treating hemifacial spasm control its symptoms but the condition is often complicated by facial weakness. We undertook this study using a rat facial nerve model to determine whether peripheral glycerol injection could be recommended as a feasible and safe technique in the management of hemifacial spasm. The animals were given a perineural application of glycerol on the facial nerve and killed at 3 days or 2 or 4 weeks after operation. The facial nerves were then examined with light and electron microscopy. Our results show that myelin disintegration and axolysis occurred after glycerol application and both the myelinated and unmyelinated fibers were affected at random, although the most striking histological changes were seen in the myelinated fibers. No evidence of persistent facial weakness in the animals was associated with this method. PMID- 11770002 TI - Regulation of human extraneuronal monoamine transporter (hEMT) expressed in HEK293 cells by intracellular second messenger systems. AB - Several transmembrane transporters of organic compounds are regulated by phosphorylation/dephosphorylation mechanisms. The aim of this study was to investigate the possible regulation of the human extraneuronal monoamine transporter, hEMT, by these mechanisms. The experiments were performed using HEK293 cells stably transfected with pcDNA3hEMT (293hEMT). The characteristics of hEMT-mediated uptake of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) were studied by incubating the cells at 37 degrees C for 1 min with 200 nM [3H]MPP+. Uptake of [3H]MPP+ by 293hEMT cells was not affected or only slightly reduced by modulators of protein kinase A, protein kinase C, or protein kinase G. It was not affected by an inhibitor of protein tyrosine kinase and was reduced by mitogen-activated protein kinase inhibitors. Uptake of [3H]MPP+ by 293hEMT cells was independent of extracellular Ca2+ and strongly reduced by Ca2+/calmodulin pathway inhibitors. Uptake of [3H]MPP+ by 293hEMT cells was strongly reduced in the presence of non selective phosphodiesterase inhibitors (IBMX, caffeine, theophylline). The effect of IBMX was independent of extracellular Ca2+ its IC50 was found to be 82.0 microM (66.2-101.6 microM; n=4), and its inhibitory effect resulted from a significant decrease in the maximal velocity of [3H]MPP+ uptake, with no change in the Michaelis-Menten constant. [3H]MPP+ uptake was reduced by 8-methoxy-methyl IBMX, a selective inhibitor of the Ca2+/calmodulin-dependent phosphodiesterase (PDE1), but not by zaprinast, a selective inhibitor of PDE5. Uptake of [3H]MPP+ by 293hEMT cells was strongly reduced by protein tyrosine phosphatase inhibitors, by an alkaline phosphatase inhibitor and, by contrast. showed an increase in the presence of exogenous alkaline phosphatase. In conclusion, these results suggest that hEMT is regulated by phosphorylation/dephosphorylation mechanisms, being active in the dephosphorylated state. PMID- 11770003 TI - Site of action of moxonidine in the rat nephron. AB - Moxonidine is a centrally acting antihypertensive agent which has been found to exert its blood pressure lowering effect by interaction with (alpha2 adrenoceptors and imidazoline receptors of the I(1)-type. These receptors have also been demonstrated to be present in the rat kidney. In the present study, clearance and micropuncture techniques were applied to anaesthetized rats to localize the site of action of moxonidine within the nephron. The clearance data show that moxonidine (0.25 mg/kg i.v., followed by a continuous i.v. infusion of 0.25 mg/h) induced a marked increase in urine flow and urinary excretion of sodium, chloride and potassium. The changes in urine flow and urinary solute excretion were accompanied by an enhanced glomerular filtration rate. The micropuncture experiments revealed that moxonidine significantly increased glomerular filtration rate of superficial nephrons, and significantly inhibited fractional reabsorption of fluid, sodium, potassium and chloride by similar amounts (by 9.0%-9.8%) in superficial proximal tubules. Regarding fluid and sodium reabsorption, the proximal effect of moxonidine was continuously weakened by a compensatory increase of reabsorption in the loop of Henle and the subsequent distal nephron segments. The inhibitory effect of moxonidine on fractional proximal potassium reabsorption was completely compensated in the loop of Henle, but the drug induced a net secretion of potassium into the segments lying beyond the early distal tubule, probably as a consequence of the increased tubule fluid and sodium load delivered to them. The experiments have identified the proximal tubule as the principal nephron site where the diuretic action of moxonidine arises. The proximal effect may be related to the increased glomerular filtration rate and to a direct inhibitory interaction of moxonidine with the proximal Na+/H+ exchanger. PMID- 11770004 TI - Non-specific caspase inhibition reduces infarct size and improves post-ischaemic recovery in isolated ischaemic/reperfused rat hearts. AB - Myocardial ischaemia and reperfusion lead to myocardial cell death due, at least in part, to apoptotic mechanisms. Although cysteinyl aspartate-specific proteinase (caspase) activation is a major event and the most-cited culprit in the development of apoptosis, its potential contribution to ischaemic myocardial cell death is largely unknown. To study the role of caspase activation, isolated rat hearts (n=6 per group) were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion. A non-selective [0.1 or 0.5 microM acetyl-Tyr Val-Ala-Asp chloromethylketone (YVAD-cmk)] or selective caspase inhibitors [0.07 or 0.2 microM acetyl-Asp-Glu-Val-Asp-cmk (Ac-DEVD-cmk, caspase-3 inhibitor); 0.07 or 0.2 microM benzoxycarbonyl-Leu-Glu-OMe-His-Asp(OMe)-fluoromethylketone (z-LEHD fmk, caspase-9 inhibitor)] were added to the perfusate at the start of reperfusion. Non-selective caspase inhibition with 0.1 or 0.5 microM YVAD-cmk limited infarct size: (21 +/- 4%, P<0.05; 17 +/- 3%, P<0.05, respectively) compared with the ischaemic/reperfused control (32 +/- 5%). In hearts treated with 0.1 or 0.5 microM caspase II non-selective inhibitor, the fraction of terminal-deoxynucleotidyl-transferase deoxyuridine nick end labelling (TUNEL) positive myocyte nuclei in the infarcted zone was reduced from the ischaemic/reperfused non-treated control of 11.2 +/- 2.1% to 6.2 +/- 1.6% (P<0.05) and 1.2 +/- 0.2% (P<0.05), respectively. The recovery of post-ischaemic cardiac function (coronary flow, aortic flow and left-ventricular developed pressure) improved significantly with the application of the non-selective caspase inhibitor as well. In hearts perfused with specific caspase inhibitors (caspase-3 and caspase-9) there was no significant reduction in the infarct size, no improvement in post-ischaemic cardiac function and no reduction of apoptotic cell death. We conclude that non-specific inhibition of caspases may be therapeutically beneficial in myocardial ischaemia/reperfusion-induced damage, while selective caspase inhibitors may fail to prevent such reperfusion-induced injury in our model system. PMID- 11770005 TI - Histamine-induced Ca2+ release in bovine adrenal chromaffin cells. AB - The histamine-induced biphasic increase of the intracellular free [Ca2+] ([Ca2+]i) was studied in bovine adrenal chromaffin cells using fura-2 microfluorimetry and the whole-cell patch-clamp technique. Both the rapid, transient Ca2+ rise and the sustained plateau component of elevated [Ca2+]i were independent of extracellular Ca2+. Incubation with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) blocker thapsigargin diminished histamine-induced changes in [Ca2+]i. When Ca2+ release was either stimulated by IP3 or blocked with the competitive inhibitor heparin, histamine was unable to elicit the typical Ca2+ rise. Ryanodine, tetracaine and ruthenium red, all blockers of Ca2+ release from caffeine-sensitive stores, had only minor effects on the agonist induced Ca2+ changes. The contribution of mitochondria in shaping the histamine induced Ca2+ increase was studied using ruthenium red and the two proton ionophores carbonylcyanide m-chlorophenylhydrazone (CCCP) and carbonylcyanide p (trifluoromethoxy)phenylhydrazone (FCCP). Both mitochondrial uncouplers reversibly increased [Ca2+]i and induced an inward current leading to cell membrane depolarisation. In summary, these results indicate that Ca2+ from IP3 sensitive stores is essential for the generation of both the transient increase and secondary elevation in [Ca2+]i. PMID- 11770006 TI - Nitrergic relaxation in urethral smooth muscle: involvement of potassium channels and alternative redox forms of NO. AB - We examined the contribution of K+ channels to the relaxation responses induced by different redox forms of nitric oxide (NO., NO- and NO+) in comparison with those evoked by electrical field stimulation (EFS) of nitrergic nerves in the sheep urethra. K+ channel blockers with different selectivity profile were used. Sodium nitroprusside (SNP) and different S-nitrosothiols were used as NO+ donors, Angeli's salt as an NO- donor and nitroglycerin (GTN) was chosen as a representative compound known to require metabolic activation in the target tissue. Pure NO gas was used to prepare NO. solutions. Relaxation evoked by EFS of nitrergic nerves or by exogenous NO was not inhibited by any of the K+ channel blockers, but was enhanced by 4-aminopyridine [inhibitor of voltage-dependent K+ (KV) channels]. This suggests that, whereas K+ channel activation and hyperpolarization of the postsynaptic membrane do not contribute to relaxation, prejunctional modulation of the nitrergic neurotransmission by Kv channels may be relevant. Relaxation induced by NO+ or NO- donors was not affected by K+ channel blockade with the following exceptions: glybenclamide, a blocker of ATP-sensitive K+ channels (KATP), enhanced responses to SNP and Angeli's salt, 4-aminopyridine inhibited relaxation evoked by Angeli's salt and GTN, and charybdotoxin, a blocker of large-conductance, Ca2+-activated K+ channels (BKCa) inhibited those induced by the S-nitrosothiol S-nitrosoglutathione. These results do not suggest the existence of a general mechanism of action on K+ channels for compounds releasing either NO+ or NO- in the sheep urethra. None of the K+ channel blockers affected relaxation induced by the membrane-permeable analogue of cGMP, 8-bromo cGMP. However, the fact that the addition of the phosphodiesterase inhibitor zaprinast (0.1 mM) enhanced the relaxation to Angeli's salt, while preventing the inhibition induced by 4-aminopyridine, suggests that involvement of guanylate cyclase activation in the action of NO donors on K+ channels can not be excluded. Accordingly, the guanylate cyclase inhibitors 1H-[1,2,4]-oxadiazole-[4,3-a] quinoxalin-1-one (ODQ, 10 microM) and 4H-8-bromo-1,2,4-oxadiazolo(3,4 d)benz(b)(1,4)oxazin-1-one (NS 2028, 10 microM) almost abolished relaxations to EFS and Angeli's salt. In contrast, ODQ only moderately inhibited relaxations to NO.. In addition, the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO) effectively inhibited responses to NO. whilst not affecting those to EFS or NO-, suggesting a close similarity between the nitrergic transmitter and nitroxyl ion. We conclude that nitrergic relaxation induced either by the endogenous transmitter or by exogenous NO donors in the ovine urethra is not mediated by postsynaptic alterations in the K+ conductance; only a prejunctional modulation through Kv channels seems to be significant. In addition, the production and/or release of alternative redox forms of NO, such as NO-, may be involved in neurotransmission processes in the urethra. PMID- 11770007 TI - How to express pharmacological contractions of the inflamed rat intestine. AB - Inflammation leads to intestinal dysmotility which can be due to both functional and trophic alterations of the neuromuscular apparatus. To discriminate between trophic and functional changes, several normalization procedures are used in contractility studies. It is important to know how normalization procedures may influence the obtained results. In a rat model of TNBS-induced ileitis, we compared seven known normalization procedures for pharmacological contractions of longitudinal muscle strips. During acute ileitis, contractility was significantly decreased, irrespective of the normalization procedure used. During the post inflammation phase, hypertrophy and hyperplasia of smooth muscle cells led to increased contractility on raw strip chart recordings. However, when contractions were corrected for the increase in muscle mass, the contractility was either normal or decreased, depending on the normalization procedure used. Normalization of contractions to the cross-sectional area (CSA) of the longitudinal muscle is the gold standard. Comparison of three methods to determine the CSA, showed that the commonly used equation to calculate the CSA, based on the tissue weight, length and density, might overestimate the CSA. We conclude that this equation should be adapted by a muscle thickness ratio, or alternatively the CSA can be determined on histological sections. PMID- 11770008 TI - Effects of acetaminophen on monoaminergic systems in the rat central nervous system. AB - Although acetaminophen is a well established analgesic, its mechanism of action is still unknown. We investigated whether this drug could affect central monoaminergic neurotransmission in rats. Significant increases in serotonin (5 HT) levels were found in the posterior cortex, hypothalamus, striatum, hippocampus and brain stem, but not spinal cord, 45 min after per os administration of 200-400 mg/kg of acetaminophen. However, this treatment altered neither the levels of 5-hydroxyindoleacetic acid nor the accumulation of 5 hydroxytryptophan after blockade of aromatic L-amino acid decarboxylase. On the other hand, a decrease in both the levels of the dopamine (DA) metabolite, dihydroxyphenylacetic acid, and the accumulation of dihydroxyphenylalanine were noted in the striatum of acetaminophen-treated rats. Finally, acetaminophen administration significantly increased noradrenaline (NA) levels in the posterior cortex. In vitro studies showed that acetaminophen (1 mM) enhanced K+-evoked overflow of [3H]5-HT, but not [3H]DA and [3H]NA, previously taken up in brain slices, and exerted no direct effect on monoamine oxidase A, tyrosine hydroxylase and catechol-O-methyl-transferase activities. These results indicate that acetaminophen affects central monoaminergic neurotransmission, thereby suggesting that monoamines (especially 5-HT) might participate in its analgesic action. PMID- 11770009 TI - MaxiK channel-mediated relaxation of guinea-pig aorta following stimulation of IP receptor with beraprost via cyclic AMP-dependent and -independent mechanisms. AB - The present study was aimed to elucidate the cellular pathway(s) controlling vascular relaxation triggered by stimulation of prostaglandin I2 (PGI2, IP) receptor with a stable PGI2 analog, beraprost. Beraprost caused a concentration dependent relaxation in de-endothelialized guinea-pig aorta contracted with prostaglandin F2alpha (PGF2alpha). Beraprost-induced relaxation was almost abolished in high-KCl-contracted tissue, indicating a major role of K+ conductances. In contrast to other PGI2 analogs (e.g. cicaprost and iloprost), beraprost-induced relaxation was practically abolished by a selective voltage and Ca2+-activated K+ (MaxiK, BK) channel blocker Iberiotoxin (10(-7) M) or by tetraethylammonium (2 x 10(-3) M). The relaxation induced by beraprost was not significantly affected by other K+ channel blockers glibenclamide (10(-6) M) or Ba2+ (10(-5) M), but was slightly attenuated by 4-aminopyridine (10(-4) M). Beraprost increased intracellular cyclic AMP levels, suggesting a role for cyclic AMP-dependent pathways. A selective inhibitor of cyclic AMP-specific phosphodiesterase, RO-20-1724 (10(-4) M), significantly potentiated beraprost induced relaxation. Iberiotoxin (10(-7) M) completely counteracted this potentiation. Moreover, tension decrement due to forskolin (3 x 10(-7) M) or 8 bromo-cyclic AMP (10(-2) M) was thoroughly restored by Iberiotoxin (10(-7) M), confirming a role for a cyclic AMP-dependent mechanism. However, SQ 22,536 (10( 4) M), an adenylyl cyclase inhibitor, did not affect beraprost-induced relaxation though it almost totally inhibited the elevation of cyclic AMP contents induced by beraprost, suggesting the existence of an additional mechanism that is cyclic AMP-independent. Moreover, cholera toxin (CTX, 1 microg/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), significantly suppressed PGF2alpha-induced contraction both in the absence and presence of SQ 22,536 (10(-4) M). Iberiotoxin (10(-7) M) was also capable of restoring the relaxation induced by CTX. These findings suggest that MaxiK channel plays a primary role in mediating smooth muscle relaxation following stimulation of IP receptor with beraprost in guinea-pig aorta. Both cyclic AMP-dependent and independent pathways contribute to the MaxiK channel-mediated relaxation following IP receptor stimulation in this vascular tissue. Direct regulation of MaxiK channels by Gs may partly account for the cyclic AMP-independent relaxant mechanism. PMID- 11770010 TI - Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. AB - Proton pump inhibitors are a class of drugs which are widely prescribed for acid related diseases. They are primarily metabolized by CYP2C19 and CYP3A4. It is unknown so far whether proton pump inhibitors are also substrates of the ATP dependent efflux transporter P-glycoprotein. Moreover, it is not established whether proton pump inhibitors are also inhibitors of P-glycoprotein function. The aim of our study was therefore to characterize omeprazole, lansoprazole and pantoprazole as P-glycoprotein substrates and inhibitors. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells. Inhibition of P-glycoprotein-mediated transport was determined using the cyclosporine analogue PSC-833 (valspodar) as P-glycoprotein inhibitor. Inhibition of efflux transport by omeprazole, lansoprazole and pantoprazole was assessed using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, basal to-apical transport of omeprazole, lansoprazole and pantoprazole was greater than apical-to-basal transport in Caco-2 and L-MDRI cells. Addition of PSC-833 (1 microM) showed a clear effect only for lansoprazole, suggesting that other transporters contribute to omeprazole and pantoprazole cellular translocation. Furthermore, all of the tested compounds inhibited digoxin transport with IC50 values of 17.7, 17.9 and 62.8 microM for omeprazole, pantoprazole and lansoprazole, respectively. In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo. PMID- 11770011 TI - Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells. AB - Previous studies demonstrated that theophylline modulates NF-kappaB activation in mast cells and pulmonary epithelial cells. We examined whether or not this modulation of NF-kappaB activation by theophylline is due to inhibition of the degradation of the IKBalpha protein, which suppresses NF-kappaB activation. TNF alpha-induced NF-kappaB activation in a human pulmonary epithelial cell line (A549) was evaluated by Western blotting and a chloramphenicol acetyltransferase (CAT) assay. Expression of the IkappaBalpha protein was evaluated by Western blotting. Western blotting of nuclear extracts of A549 cells demonstrated that theophylline suppresses NF-kappaB-p65 nuclear translocation. The CAT assay indicated that NF-kappaB-dependent reporter gene expression is inhibited in A549 cells pretreated with theophylline. Western blotting of cytoplasmic extracts of A549 cells revealed that this inhibition was linked to theophylline-induced protection of expression of the IkappaBalpha protein. Moreover, theophylline inhibited interleukin-6 production induced by TNF-alpha in A549 cells. These findings are consistent with the idea that theophylline suppresses the production of proinflammatory cytokines via inhibition of NF-kappaB activation through protection of the IkappaBalpha protein. PMID- 11770012 TI - Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats. AB - In anaesthetized rats activation of vanilloid receptors on sensory vagal nerves elicits rapid bradycardia and hypotension (Bezold-Jarisch reflex). Recent in vitro experiments revealed that the endogenous cannabinoid ligand anandamide acts as an agonist at the vanilloid VRI receptors. The present study was aimed at examining whether vanilloid VR1 receptors are involved in the cardiovascular effects of anandamide in the anaesthetized rat. Intravenous injection of anandamide, its stable analogue methanandamide and the vanilloid receptor agonist capsaicin produced a dose-dependent immediate and short-lasting decrease in heart rate and blood pressure with the following rank order of potencies: capsaicin > methanandamide > anandamide. This bradycardia was dose-dependently diminished by the selective vanilloid receptor antagonist capsazepine (0.3-3 micromol/kg) and the nonselective inhibitor of these receptors, ruthenium red (1-10 micromol/kg). Both antagonists reduced or tended to reduce the hypotension stimulated by the agonists. Following this bradycardia and hypotension (presumably evoked by the Bezold-Jarisch reflex; phase I), capsaicin, anandamide and methanandamide led to a brief vasopressor effect (phase II). Subsequently both anandamides, but not capsaicin, induced a more prolonged decrease in blood pressure (phase III). Capsazepine and ruthenium red (at doses up to 3 tmol/kg and 10 micromol/kg, respectively) failed to affect these changes in blood pressure. The cannabinoid CB1 receptor antagonist SR 141716 at 3 micromol/kg abolished the prolonged decrease in blood pressure (phase III) induced by anandamide and methanandamide, but had no effect on the reflex bradycardia and hypotension (phase I) and on the subsequent vasopressor effect (phase II) evoked by capsaicin, anandamide and methanandamide. In conclusion, the endogenous cannabinoid receptor agonist anandamide and its stable analogue methanandamide induce reflex bradycardia and hypotension (phase I) by activating the vanilloid VRI receptor. Whereas the mechanism underlying the brief vasopressor effect (phase II) is unknown, the prolonged hypotension (phase III) results from stimulation of the cannabinoid CB1 receptor. PMID- 11770013 TI - Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by beta 2-adrenoceptors. AB - The mechanism by which 2(3H)-benzothiazolone, 4-hydroxy-7-[2-[[2-[[3-(2 phenylethoxy)propyl]-sulphonyl]ethyl]amino]ethyl]-monohydrochloride (AR-C68397AA; viozan), a dual dopamine D2/beta2-adrenoceptor agonist which has shown promise in the treatment of chronic obstructive pulmonary disease (COPD), inhibits the extravasation of plasma protein induced by capsaicin in the tracheas of Brown Norway rats has been re-evaluated. Viozan (10-30 microg/kg given intratracheally; i.t.) inhibited dose-dependently the extravasation of plasma protein tagged with Evans Blue into rat trachea induced by capsaicin (10 microg/kg i.t.). Similar effects were seen with the selective beta2-adrenoceptor agonist, salbutamol (3-10 microg/kg i.t.), but the selective dopamine D2 receptor agonist, quinagolide (10 30 microg/kg i.t.), was inactive. The effects of viozan and salbutamol were abolished by propranolol (3 mg/kg) given intraperitoneally (i.p.) but unaffected by sulpiride (3 mg/kg i.p.). Thus, in c,ontrast to claims in the literature, a functional response to dopamine D2 receptor activation in a preclinical model of oedema arising from sensory nerve fibre activation in the rat lung could not be demonstrated. Moreover, no qualitative difference could be demonstrated between the response to a dual D2/beta2-adrenoceptor agonist and a selective beta2 adrenoceptor agonist. The observations call into question whether a dual D2/beta2 adrenoceptor agonist such as viozan would bring added benefit over established selective beta2-adrenoceptor agonists in the therapy PMID- 11770014 TI - The beta 2 subunit of nitric oxide-sensitive guanylyl cyclase is developmentally regulated in rat kidney. AB - We have recently shown that nitric oxide activates the beta2 subunit of soluble guanylyl cyclase. In the present study, we show developmental regulation of this subunit. Analysis of mRNA expression by RT-PCR and RNase protection analysis in kidneys revealed no expression of the beta2 subunit in neonatal and strong expression in adult rats. A reciprocal regulation with much lower expression levels was observed in rat lung. Further examination of kidneys from 3, 6, 16, 22, 25, 31 and 36-day-old rats showed that significant expression appears between postnatal day 16 and 22. Isolation of the rat beta2 promoter by genome walking and cloning into a reporter gene vector showed promoter activity for the sense but not the antisense construct providing an in vitro assay for further analysis of the developmental beta2 subunit regulation. PMID- 11770015 TI - Sanguinarine induces bimodal cell death in K562 but not in high Bcl-2-expressing JM1 cells. AB - Our previous studies with low Bcl-2-expressing K562 cells have shown that, when treated with the putative anti-cancer drug sanguinarine, concentrations of 1.5 microg/ml induced the morphology of apoptosis or programmed cell death (PCD), while concentrations of 12.5 microg/ml induced a morphology of blister formation or blister cell death (BCD). To elucidate the possible role of Bcl-2 in this dual cell death modality induced by sanguinarine, K562 and the high Bcl-2-expressing JM1 cells were treated with sanguinarine concentrations of 1.5 microg/ml and 12.5 microg/ml respectively, and multiple parameters of their effects were studied using light and electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, 51Cr release, trypan blue exclusion, propidium iodide exclusion, and annexin-V binding. In general, we found that, while K562 cells underwent PCD and BCD when treated with sanguinarine, JM1 cells failed to undergo either PCD or BCD under the same experimental conditions. Thus, the over-expression of anti apoptotic Bcl-2 may have prevented sanguinarine from inducing PCD and BCD in JM1 cells. These results indicate that the resistance of JM1 cells to the alkaloid sanguinarine may have been due to an anti-BCD role played by Bcl-2, in addition to its widely reported anti-apoptotic role. PMID- 11770016 TI - Histological evaluation of multiple testicular biopsies helping assisted reproduction. AB - Because of the fall in population in Europe, the evaluation of causes of male infertility is becoming more and more important. Testicular biopsy is a useful method of examination in the area of assisted reproduction. Testicular biopsies of 85 infertile males were evaluated histologically. According to the sperm count, 31 patients had azoospermia, 22 oligo-astheno-teratozoospermia (OATS), 29 oligozoospermia, and 3 astheno-teratozoospermia. The biopsies were carried out by atraumatic microsurgery. Samples were taken from the upper inner and lower outer quadrant of both sides. Bouin-fixed, paraffin-embedded blocks were cut and HE slides examined. Samples taken from azoospermic patients showed atrophy, maturation arrest, normal histology or Sertoli cell-only syndrome. Oligozoospermic patients presented maturation arrest, hypospermatogenesis or normal histology. In the OATS group maturation arrest hypospermatogenesis and atrophy were found. The spermatogram groups showed significant correlation with the homogeneity of the spermatogenesis. The sperm count alone is not sufficient in assessing spermatogenesis. Four samples give more adequate information than just one, because spermatogenesis is not homogeneous in the testis. After evaluating diagnostic biopsies, tissue for TESE can be taken from the most appropriate location in the testis. PMID- 11770017 TI - Different keratin profiles in craniopharyngioma subtypes and ameloblastomas. AB - Craniopharyngiomas are generally considered to arise from the remnants of Rathke's pouch or a misplaced enamel organ. We tried to refine these hypotheses, comparing the subtypes of craniopharyngioma with Rathke's cleft cyst, a known Rathke's pouch derivative, and with ameloblastoma, an enamel organ derivative. Nineteen craniopharyngiomas (14 adamantinomatous and 5 papillary type tumors) and 17 ameloblastomas were immunostained for cytokeratin (CK) 7, CK 8, CK 14, and human hair keratin (HHK). All cases of adamantinomatous craniopharyngioma were CK 7+/CK 8+/CK 14+. Two cases (40%) of papillary craniopharyngioma were CK 7+/CK 8+/CK 14+, whereas the remaining three cases (60%) were CK 7+/CK 8-/CK 14+. Fifteen cases (88%) of ameloblastoma were CK 7-/CK 8+/CK 14+. Only the shadow cells present in adamantinomatous craniopharyngiomas were positive for HHK, which may indicate their follicular differentiation. In Rathke's cleft cyst, ciliated cuboidal cells were CK 7+/CK 8+/CK 14- and metaplastic squamous cells were CK 7+/CK 8/CK 14+. These findings suggest that both subtypes of craniopharyngioma may differ from ameloblastoma in histogenesis, although cytokeratin expression patterns may change during tumor development. Adamantinomatous craniopharyngioma may be related to a heterotopic ectodermal tissue which can differentiate into hair follicles, while papillary craniopharyngioma may arise from Rathke's cleft cyst. PMID- 11770018 TI - Acinar phenotypes in salivary pleomorphic adenoma: unusual differentiation or disordered functional activity? AB - To explain the occurrence in salivary pleomorphic adenoma of structures with an arrangement and appearance of tumour cells resembling acini, two tumours showing such structures and, for comparison, a tumour showing goblet cells were examined with the use of histochemistry and immunocytochemistry for constituents of the salivary secretory process. One tumour consisted mainly of slightly granular cells with an acinar arrangement, which contained neutral and carboxylated glycoproteins, -SH groups and cytoplasmic epithelial membrane antigen. The second tumour showed a minor component of structures resembling mucous acini, which contained neutral and carboxylated glycoproteins, -SS- groups and fucoglycoconjugates. The goblet cells of the third tumour contained sulphated glycoproteins and were associated with cystic lumina. Acinar phenotypes in salivary pleomorphic adenoma could reflect either an unusual line of differentiation or luminal cells with increased synthesis and/or retention of variably mature glycoproteins different from those of goblet cells. Disordered secretion and externalization of glycoproteins are possible factors influencing phenotypes in this tumour. PMID- 11770019 TI - Chylomicron retention disease--the role of ultrastructural examination in differential diagnosis. AB - Three children with malabsorption presumably caused by celiac disease had undergone jejunal biopsy. While a histological examination revealed microvacuolization of enterocytes in the absence of celiac lesions, an ultrastructural investigation disclosed numerous chylomicrons and larger lipid vacuoles inside the cytoplasm of enterocytes, mostly in the supranuclear region. No chylomicrons were evident in the interstitium between adjacent enterocytes, as observed in normal subjects. These ultrastructural findings allowed for the diagnosis of "Chylomicron retention disease" (CRD). CRD was described for the first time by Anderson in 1961, and it is included in the group of disorders of biosynthesis and secretion of B apolipoproteins (apoB). This disease, in particular, appears to result from a specific defect involving the secretion of lipoproteins containing apoB-48 from the gut, with the complete absence of post prandial chylomicrons in the sera. CRD needs to be recognized early because of its adverse effects on growth and its potential for neurological and ocular complications, and the ultrastructural identification of chylomicron-size lipid droplets clustered in the enterocytes, with the absence of fat outside the cells, represents the gold standard to identify CRD. together with clinical aspects and laboratory measurements. In this study, we describe the histological and ultrastructural aspects observed in three pediatric cases of CRD. PMID- 11770020 TI - A case report of early idiopathic portal hypertension. AB - We report herein a case (46 years, female) of very early idiopathic portal hypertension. During an examination for in situ uterine cervical cancer, splenomegaly and hypersplenism were incidentally found. CT and MRI showed a nonatrophic liver with dilated portal veins and marked splenomegaly. The portal venous blood flow was increased, while portal venous blood pressure was not high. The spleen (1,220 g) showed hyperplasia of white pulp and congestion. The lobular architecture of the liver was well-preserved, and the subcapsular regions were not atrophic or dropped out. The portal tracts were not fibrotic, and portal veins were neither stenotic nor sclerotic. Instead, lymphoid cell infiltrations were found in about half the portal tracts, and there was subendothelial mononuclear cell infiltration of small portal vein branches. The hepatic lobules showed non-specific reactive change. This case suggests that early hepatic changes recognizable histologically in this disease are lymphoid cell infiltration of the portal tract and of subendothelial regions of portal vein branches, and nonspecific lobular hepatitis. These hepatic changes, as well as marked splenomegaly, may represent an altered immunophenomenon of this disease. PMID- 11770021 TI - Dysembryoplastic neuroepithelial tumors: report of 10 cases from a center where epilepsy surgery is not done. AB - Dysembryoplastic neuroepithelial tumor (DNT) is a recently recognized tumor entity with distinctive clinicopathological features and an excellent long-term prognosis. We report 10 cases of DNT out of neurosurgical specimens sent for histopathological examination since 1994. Epilepsy surgery is not done at our center, and all the cases were sent with a clinical diagnosis of glioma. On histopathological examination, all the 10 cases contained the specific glioneuronal element. In 6 cases, glial nodules were noted in addition. This study therefore reports 4 cases of simple DNT and 6 cases of complex DNT. There was no nuclear atypia or mitosis in any of the cases. Proliferative index by PCNA varied from negative to <1%. It is very important to recognize this entity, as surgery cures the patient, and radiotherapy or chemotherapy is not required. PMID- 11770022 TI - Primary fibromatosis of the breast in a patient with multiple desmoid tumors- report of a case with evaluation of estrogen and progesterone receptors. AB - Fibromatosis (or desmoid tumor) is an infiltrative fibroblastic/myofibroblastic lesion presenting a moderate risk for local recurrence and no metastatic potential. Classically, these lesions are classified whether in abdominal or extra-abdominal sites, and may be multicentric or familial. Primary fibromatosis of the breast (PFB) is an uncommon lesion that shows histological similarities with abdominal fibromatosis (AF), and frequently poses difficulties in the differential diagnosis with other spindle cell tumors of the breast. It has been demonstrated that AF usually shows immunoreactivity for estrogen (ER) and progesterone (PR) receptors; conversely, in most of the studies, the cells from PFB are consistently negative for both receptors. We report on a case of a 41 year-old female with two desmoid tumors, affecting the abdominal wall and the breast tissue. To the best of our knowledge, there is no previous report in which hormonal receptors were evaluated in abdominal and mammary desmoid tumors in the same patient. We assessed the immunohistochemical expression of ER and PR in both lesions; while the AF showed immunoreactivity for both receptors, the cells from PFB were all negative. Although we have considered just this case, we still believe that these findings could support a distinctive etiopathogenesis of abdominal and mammary fibromatosis. PMID- 11770023 TI - Marginal zone B cell lymphomas of Waldeyer's ring--a report of two tonsillectomy cases resembling histomorphological features of inflammatory lesions. AB - We identified two cases of lymphoma of the mucosa-associated lymphoid tissue (MALT) type in 11 tonsillectomy specimens of primary B cell lymphoma of Waldeyer's ring. Both patients were Japanese females presenting with bilateral enlargement of the palatine tonsils. One had a history of chronic otitis media. In that case, the lesion was characterized by an extrafollicular growth pattern with marginal zone-like arrangement. The tumor was mainly composed of medium sized cells with round or indented nuclei with scant cytoplasm (centrocyte-like cells). In the other patient, most tumor cells were mature plasma cells, plasmacytoid cells, proplasmacytes, and immunoblasts with scattered centrocyte like cells. Tropism of tumor cells for the epithelium was noted in both lesions. Primary marginal zone B cell lymphoma of the MALT type arising from Waldeyer's ring has rarely been reported in the literature, causing certain diagnostic problems. Various florid reactive lymphoproliferative disorders, including chronic tonsillitis and infectious mononucleosis, should be differentiated from this type of primary Waldeyer's ring lymphoma. PMID- 11770024 TI - Benign signet ring cell change with multilayering in the gallbladder mucosa--a case report. AB - We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded. PMID- 11770025 TI - Immune consequences, pathophysiology, and current perspectives of the extracorporeal circulation. PMID- 11770026 TI - Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions. AB - Cardiac surgery with cardiopulmonary bypass (CPB) is known to induce an immune response whose nature has been increasingly elucidated during the recent decade. Clinically, patients usually show two to three of the four symptoms, which define the so-called systemic inflammatory response syndrome (SIRS). In addition, all parameters of the innate, nonspecific immune system, e.g., polymorphonuclear cells, elastase, and complement, are activated. This also applies to the proinflammatory mediators interleukin (IL)-1beta, -6, and -8, and tumor necrosis factor (TNF)-alpha. Within the adaptive, specific immune system, a decrease of T lymphocytes and T helper (TH) cells is observed, whereas suppressor/ cytotoxic T cells and B cells appear to be nearly unaffected. Cytokine measurements provide more detailed information: IL-2 and IL-12, which are important for the activation of the type-1 TH-cell (TH1)-mediated immune response, are depressed following cardiac operation. In contrast, IL-10 and transforming growth factor-beta essential to TH2-mediated humoral or anti-inflammatory immune response, are upregulated. In vivo tests, e.g., delayed type hypersensitivity skin reaction and tetanus antibody production, confirm the polarization of the adaptive immune response towards the TH2 pathway. However, all these alterations usually do not result in clinical adverse events. Therefore, more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response. For this purpose, more readily available, standardized methods for immunologic monitoring appear highly desirable. PMID- 11770027 TI - Cardiopulmonary bypass and cerebral injury in adults. AB - Cerebral injury after cardiac surgery is still a major cause of mortality and morbidity after cardiac surgery. In an aging patient population the incidence is likely to increase. Comparisons between cardiac and other major surgery suggested that cardiopulmonary bypass (CPB) causes the neurological sequelae. Strategies to avoid brain injury target the reduction of emboli floating in the cerebral circulation, adequacy of cerebral oxygenation, and minimization of the whole body inflammatory response to the bypass circuit. Experimental and clinical studies demonstrated that manipulation of CPB can reduce abundant cerebral blood flow and the embolic load to the brain. Hematocrit, temperature, blood pressure, and acid base status during CPB are parameters that have impact on the neurological outcome and can be optimized. Other possibilities to avoid cerebral complications include improvements of surgical techniques and devices or the application of new therapeutic drugs. However, further experimental studies and, most importantly, prospective randomized clinical trials are warranted to prove new innovative concepts in clinical practice. PMID- 11770028 TI - Strategies to improve myocardial protection during extracorporeal circulation. AB - A recent survey of outcomes in 8,641 patients who underwent coronary artery bypass grafting (CABG) operations in northern New England indicates an overall mortality of 4.48%. (1) Importantly, 65% of all deaths could be directly attributed to postoperative heart failure. These data indicate that in spite of the dramatic improvements in myocardial protection that have been accomplished over the past decades, there is still room for improvement, in particular in high risk patients who may poorly tolerate superimposition of perioperative ischemic damage on their underlying critical hemodynamic status. This paper reviews the major techniques in current clinical use with more emphasis on recent advances and possible perspectives. From a practical standpoint, a distinction can be made between strategies directly targeted at the myocardium and strategies that can indirectly enhance cardioprotection by attenuating the systemic inflammatory effects of cardiopulmonary bypass (CPB). These different approaches will thus be reviewed consecutively. PMID- 11770029 TI - Pediatric cardiac surgery with cardiopulmonary bypass: pathways contributing to transient systemic immune suppression. AB - Cardiovascular surgery with cardiopulmonary bypass (CPB) can lead to postoperative complications like postpericardiotomy syndrome (PPS), capillary leak syndrome, or multiple organ failure. In children, PPS morbidity is up to 30%, and intra- and immediate postoperative mortality is up to 4%. For these complications, the CPB is made responsible. Its etiology is not yet clarified in detail, but is thought to be of immunologic origin. The exact knowledge of these reactions is crucial for the selection of treatment strategies. The immune response to CPB surgery in children comprises of a cascade of pro- and anti inflammatory events. Proinflammatory responses are indicated by the release of interleukin (IL)-6 and IL-8, and the activation of alternative complement pathway. This reaction is mainly a response to surgical trauma and medication and only activation of the alternative complement pathway is CPB specific. Antiinflammatory response during CPB surgery is serologically indicated by the systemic release of the immunosuppressive cytokine IL-10 already before that of proinflammatory cytokines. CPB surgery induces population shifts of the leukocyte subsets, changes their degree of activation, and contributes to the phenotype of a peripheral immune suppression. Circulating neutrophils are selectively filtered and inactivated. T-helper (Th) cells shift transiently to the Th2 phenotype, indicating the prevalence for a humoral immune response. These alterations start immediately after the onset of the CPB. Increased immunosuppression may be involved in PPS development and may be linked to an allergic/atopic predisposition. A generalized model of the immune sequela to pediatric cardiovascular surgery with CPB is drawn. CPB induces a systemic transient anti inflammatory response by elimination of activated cells, by compensatory reaction to local, systemically not observable, proinflammatory responses, by IL-10 release, by anesthetics and medication, and by leukocyte extravasation. The subsequent proinflammatory reaction is the reaction to surgical trauma modulating the anti-inflammatory reaction. Possible therapeutic consequences of these findings may include treatment strategies that modulate the anti-inflammatory response. More studies are needed to test this hypothesis. PMID- 11770030 TI - Interleukin-1 and related proteins in cardiovascular disease in adults and children. AB - Interleukin-1 (IL-1) is a key mediator in the cytokine network, controlling important functions in the immune system, during development, infection, inflammation, cell-differentiation, tissue remodelling, and even cell death. The agonistic isoforms of IL-1 (i.e., IL-1alpha and IL-1beta), the IL-1 receptor antagonists, the receptors and receptor-associated proteins, as well as the recently identified IL-18 and its receptor belong to the IL-1 family of proteins. Activation of the IL-1beta and IL-18 precursors is performed enzymatically by caspase-1, previously termed IL-1beta-converting enzyme (ICE). This molecule is the founding member of the caspase family of enzymes, which are involved in maturation of cytokines and in initiation and execution of apoptotic processes. It has been suggested that cytokines and apoptosis are involved in pathogenesis of cardiovascular diseases such as atherosclerosis, chronic heart failure, myocarditis, cardiomyopathy, or stroke. Since IL-1, like TNF, is a central mediator in the cytokine network, it may act as a potent activator of cardiovascular cells. We know that cells of the vessel wall and the heart can produce IL-1 and respond to this mediator by production of other cytokines or regulation of other cardiovascular cell functions. Thus, this report summarizes general information about the molecules of the IL-1 family of proteins, including the caspases, as well as data regarding these proteins in relation to the vessel wall and the heart and their role in cardiovascular disease in adults and children. The summarized information indicates a role of these molecules in regulation of local inflammatory responses during cardiovascular disease. PMID- 11770031 TI - Modulating IL-6 and IL-10 levels by pharmacologic strategies and the impact of different extracorporeal circulation parameters during cardiac surgery. AB - Postoperative morbidity after coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can be influenced by pro- and anti-inflammatory cytokines like interleukin 6 (IL-6) and IL-10 triggering and balancing the acute phase response. The extent of cytokine release can be modulated by different methods. This prospective randomized study examines the effect of treatment of patients with steroid (group 1, 250 mg of prednisolone)(Solu-Decortin H)), aprotinin (group 2, 6 Mio. KIU [kallikrein inhibitory units] aprotinin [Trasylol]), and heparine coating of the artificial surface (group 3, Bioline) on the systemic release of IL-6 and IL-10 in four groups of 40 patients with coronary artery disease (CAD) scheduled for CABG. Group 4 (standard medication) served as control. Twenty hemodynamic and biochemical parameters of the CPB were analyzed regarding correlation to cytokine levels measured by enzyme-linked immunosorbent assay (ELISA). In group 1, IL-6 was suppressed compared to the control (P< 0.01). IL-10 was upregulated (P< 0.01). In group 2, cytokine release was similar to group 1. Using heparin-coated circuits in group 3 led to IL-10 upregulation (P < 0.05) and IL-6 suppression (P < 0.05). We found an exponential relationship between IL-10 levels (IL-6 levels) and cardiac ischemia time, duration of CPB, and the extent of negative base excess. An inverse relationship was found for IL-10 (IL-6) levels and venous O2 saturation (SvO2), and mean arterial pressure (MAP). Hypothermia (<34 degrees C) reduced IL-10 and IL-6 release, whereas long duration of hypothermia correlated with higher IL-10 and IL 6 release. Cytokine release after extracorporeal circulation (ECC) can be modulated pharmacologically and by distinct perfusion regimen. PMID- 11770032 TI - Endotoxemia and cytokine generation in cardiac surgery in relation to flow mode and duration of cardiopulmonary bypass. AB - We investigated whether pulsatile flow in cardiopulmonary bypass (CPB), which has been shown to improve intestinal perfusion, reduces endotoxin translocation from the gut and, in consequence, decreases cytokine generation. The study population consisted of 48 adult patients who underwent elective CPB surgery. Pulsatile flow was used during aortic cross-clamping in 24 patients and nonpulsatile flow in 24 patients. Plasma endotoxin concentration increased in all patients during CPB. Significantly (P < 0.05) lower peak levels of 8.25 +/- 1.17 (SEM) pg/mL were reached 30 min after CPB in patients with pulsatile flow in contrast to 11.26 +/- 1.42 pg/mL in patients with nonpulsatile flow. The extent of endotoxemia was not related to the duration of CPB. Following the increase of plasma endotoxin, the concentrations of IL-6 and IL-8 increased with delay of approximately 1 h. The peak levels of these cytokines corresponded significantly (P < 0.005 and P < 0.01, respectively) with duration of CPB, but not with flow mode. Thus, in patients with CPB of more than 97 min (median), IL-6 reached a peak of 335.5 +/- 48.87 pg/mL and IL-8 of 64.86 +/- 24.79 pg/mL in contrast to 210.9 +/- 18.45 pg/mL and 21.2 +/- 10.19 pg/mL, respectively, with bypass times of less than 97 min. The degree of endotoxemia in CPB mainly depends on the quality of tissue perfusion. Cytokine generation, however, is not triggered exclusively by endotoxin, but rather by the trauma of CPB and surgery. PMID- 11770033 TI - Prediction of clinical outcome after cardiac surgery: the role of cytokines, endotoxin, and anti-endotoxin core antibodies. AB - Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can lead to a systemic inflammatory response syndrome with organ failure and increased morbidity and mortality. The mechanisms of these findings are still under discussion. We investigated whether anti-endotoxin core antibodies, endotoxin, and proinflammatory cytokines influence the clinical course after cardiac surgery. Seventy-eight patients undergoing CABG using CPB were investigated. Anti-endotoxin core antibodies, endotoxin, interleukin (IL)-6, IL 8, IL-1beta, and TNF-alpha were measured 24 h preoperatively and up to 72 h postoperatively. Patients with a postoperative mechanical ventilation time below 24 h (n = 65; Group A) were compared to patients with prolonged respirator therapy (>24 h; n = 13; Group B). Preoperative antibody levels were significantly lower in Group B (P < 0.001). In this group, antibody levels remained decreased during the observation period (P < 0.001). Endotoxin significantly increased 30' postoperatively in both groups (P < 0.002). The increase in Group B was 3-fold higher (P< 0.001). IL-8 increased postoperatively in both groups, peaking 3 h after surgery (P < 0.001). In Group B, the IL-8 release was significantly higher than in Group A (P < 0.001). IL-6 significantly increased in both groups, reaching its maximum 24 h postoperatively (P < 0.001). No differences between groups were observed. No significant changes of IL-1beta and TNF-alpha were observed. We conclude that anti-endotoxin core antibodies may be predictive of adverse outcome after cardiac surgery. The imbalance between antibodies and endotoxin results in an exaggerated increase in endotoxin and IL-8 with an impact on clinical outcome. PMID- 11770034 TI - Ultrafiltration of the priming blood before cardiopulmonary bypass attenuates inflammatory response and improves postoperative clinical course in pediatric patients. AB - The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF-alpha, IL-1beta, IL-8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients. PMID- 11770035 TI - Reduction of systemic and cardiac adhesion molecule expression after off-pump versus conventional coronary artery bypass grafting. AB - Cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory mediators. We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off-pump coronary artery bypass grafting (OPCAB). Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13), or were treated conventionally using extracorporeal circulation, blood cardioplegia, and hypothermic arrest (29 degrees C-31 degrees C; n = 13). Systemic levels of TNF-alpha and the soluble adhesion molecules P-selectin and intracellular adhesion molecule 1 (ICAM-1) were assayed. Immunohistochemistry was used to account for cardiac-specific expression of adhesion molecules in interventricular endomyocardial sections. Both systemic and endomyocardial expression of adhesion molecules were lower in the OPCAB group. Coronary revascularization with CPB resulted in a significant higher expression of TNF alpha, which was associated with P-selectin and ICAM-1 expression. This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period. Despite comparable surgical trauma, the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement. Since the clinical course in the early postoperative period was comparable, larger trials are required to select the appropriate patient who benefits most from one or the other treatment regime. PMID- 11770036 TI - Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients. AB - Interleukin-18 (IL-18) appears to play a critical role in cytokine-induced organ failure during endotoxemia in animal models. Therefore, plasma samples from patients with severe trauma and sepsis were examined for the presence of IL-18. Significantly elevated plasma IL-18 concentrations were found in patients with sepsis compared to severely injured patients and healthy humans. Septic patients who died and patients with septic shock exhibited higher levels of IL-18 than survivors and septic patients without shock. In addition, septic patients with gram-positive infections had significantly higher IL-18 plasma levels than patients with gram-negative infection. These findings were confirmed by whole blood assay from healthy humans where Staphylococcus aureus markedly (P < 0.05) increased the release of IL-18 in whole blood ex vivo, while endotoxin was ineffective. Although obtained from a small patient group, these results suggest that IL-18 production may discriminate between gram-positive and gram-negative sepsis, and that increased IL-18 appearance may be associated with an adverse outcome in septic patients. PMID- 11770037 TI - Effects of mannitol on the acute lung injury induced by oleic acid in rats. AB - Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P < 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties. PMID- 11770038 TI - Increased neutrophil motility by beta-glucan in the absence of chemoattractant. AB - Systemic candidasis is a life-threatening complication of antibiotic and immunosuppressive therapies and can alter host defense mechanisms through pathways that are poorly understood. Promotion of polymorphonuclear leukocyte (PMN) chemotaxis by beta-glucan towards fMLP or IL-8 gradients demonstrates a fundamental effect on host defenses by pathogenic fungi. The aim of the present study was to determine whether recognition of beta-glucan is sufficient to alter PMN motility in the absence of agonists of G-coupled protein chemotactic receptors. Present findings demonstrate a profound increase in PMN motility by beta-glucan supplementation of a fibronectin substratum in an underagarose migration assay. Motility on beta-glucan included a 3-fold increase in distance of migration, as well as a 5-fold increase in the number of PMNs recruited into the motile phase as compared to motility on fibronectin alone. This promotion of motility is determined by the beta2 integrin complement receptor 3 (CR3) (CD11b/CD18) rather than the beta1 integrin very late antigen 3 (VLA-3), which mediates chemotaxis on beta-glucan-supplemented matrix towards fMLP. PMN motility on beta-glucan-supplemented fibronectin was selectively decreased by inhibitors of pp60 src and ras, whereas motility was promoted by inhibition of p38-MAPK. No effect of these inhibitors was seen on PMNs migrating on fibronectin alone. Migration on beta-glucan-supplemented fibronectin, but not on fibronectin alone, was negatively regulated by protein kinase C (PKC) or cAMP activation. These findings indicate that beta-glucan is sufficient to alter the migratory capacity of PMN in the absence of costimulation by fMLP. Enhanced PMN migration on beta glucan is mediated through specific integrins and second messenger pathways that are distinct from those utilized by PMNs migrating in the absence of beta-glucan. PMID- 11770039 TI - Role of IFN-gamma in bacterial containment in a model of intra-abdominal sepsis. AB - Interferon-gamma (IFN-gamma) is a specific activator of macrophage function and plays a critical role in the host immune defense to bacterial infection. In this study we examined the role of IFN-gamma in the regulation of bacterial load in the cecal ligation and puncture (CLP) model of intra-abdominal sepsis in the rat. In initial studies, levels of IL-12, MCP-1, and IFN-gamma were measured in the peritoneal lavage fluid 24 and 48 h after CLP. IL-12 and MCP-1 levels were both significantly increased at 24 h after CLP compared to sham controls and this difference was maintained at 48 h after CLP. Interestingly, IFN-gamma levels were not significantly increased 24 h after CLP, but were increased at 48 h after CLP. These results clearly suggest that although an inflammatory response had occurred 24 h post-surgery, with increases in the proinflammatory cytokine IL-12 and the potent chemotactic agent MCP-1, levels of IFN-gamma in CLP rats were similar to sham controls. To further investigate the role of IFN-gamma on the development of sepsis we examined the effect(s) of administering anti-IFN-gamma antibody on bacterial load after CLP. We show that use of anti-IFN-gamma antibody can significantly decrease bacterial load in the peritoneum. The mechanism of the effect(s) of anti-IFN-gamma is probably by increasing intestinal adhesions to seal the cecum and reduce bacterial movement into the peritoneum. PMID- 11770040 TI - Endotoxin-adapted septic shock leukocytes selectively alter production of sIL-1RA and IL-1beta. AB - During septic shock, circulating levels of anti-inflammatory mediators are increased relative to those of pro-inflammatory. The reduced capacity of septic shock blood leukocytes in expressing pro-inflammatory genes in response to bacterial lipopolysaccharide endotoxin (LPS) may contribute to reductions in these mediators, but the reasons for persistent increases in circulating anti inflammatory mediators are unknown. We determined whether septic shock leukocytes that have adapted to LPS induction of the IL-1beta gene could continue to express sIL-1RA in response to LPS. Septic shock whole-blood leukocytes and neutrophils (PMNs) selectively maintained production of sIL-1RA after treatment with LPS while limiting that of IL-1beta. Repressed transcription of IL-1beta and rapid decay of IL-1beta mRNA in septic shock neutrophils correlated with reductions in levels of IL-1beta after stimulation with LPS. Transcription of sIL-1RA mRNA was also suppressed, but the ability of LPS to stimulate events that lead to efficient translation of a stable sIL-1RA mRNA appeared responsible for maintaining sIL-1RA production. We conclude that LPS adaptation of septic shock leukocytes selectively influences signaling pathways that regulate transcription, mRNA processing, and translation, leading to changes in the balance of production of pro- and anti-inflammatory mediators. PMID- 11770041 TI - Pretreatment with a deleted form of hepatocyte growth factor (dHGF) prevents the mortality of plasma-loss-induced hypovolemic shock in rats. AB - Severe trauma, infection, burn, pancreatitis and major surgery often induce circulatory collapse leading to multiple organ failure and death. It is hypothesized that therapy for the attenuation of circulatory collapse may improve the prognosis in these diseases. Previous work has documented that pretreatment with a deleted form of hepatocyte growth factor (dHGF) in normal rats increases the circulating plasma volume that reflects its accelerating action of hepatic protein synthesis. Therefore, the effects of pretreatment with dHGF on hypovolemic shock models were studied in rats. Rats were intravenously administered dHGF (1 mg/kg, twice daily for 5-6 days) or vehicle, and subjected to a 25% total body surface area full-thickness burn or a trypsin-induced acute pancreatitis. In rats that were receiving vehicle, survival rates on day 7 after injury induction were 12% in the burn model and 5% in the pancreatitis model, respectively. In both models, hematocrit values were apparently increased and circulating plasma volumes were decreased compared to sham-operated rats at 6 h after injury induction. The pretreatment of animals with dHGF increased the survival rates on day 7 to 40% in the burn model and 29% in the pancreatitis model. dHGF-treatment in normal rats decreased the hematocrit values and increased the circulating plasma volumes, and these changes of hematocrit value and circulating plasma volume were also maintained after injury induction. These findings suggest that dHGF pretreatment prevents the mortality in the severe burn and acute pancreatitis, and that its effect may contribute to ameliorating the progressing of plasma-loss-induced hypovolemia. PMID- 11770042 TI - Differential cardiopulmonary recruitment of neutrophils during hemorrhagic shock: a role for ICAM-1? AB - Hemorrhagic shock and subsequent resuscitation can result in acute lung injury and cardiac dysfunction. Previous studies have demonstrated that tissue neutrophil accumulation contributes to cardiopulmonary injury associated with trauma. Thus, suppression of tissue neutrophil recruitment in an early therapeutic window after hemorrhagic shock may protect the cardiopulmonary system. It is unclear whether hemorrhagic shock induces cardiopulmonary recruitment of neutrophils before resuscitation. Intercellular adhesion molecule 1 (ICAM-1) is one of the important factors that mediate tissue neutrophil recruitment. The physiologic significance of ICAM-1 expression after hemorrhage before resuscitation is not well delineated. The present study examined the role of ICAM-1 in neutrophil accumulation in the heart and lung after severe hemorrhage without resuscitation. Mice were subjected to hemorrhagic shock by removal of 30% of total blood volume. Lung neutrophil number as determined by immunofluorescent staining increased by 1 h after hemorrhage and was maximal at 4 h whereas myocardial neutrophil number was not changed. Lung neutrophil accumulation was not associated with an up-regulation of ICAM-1 expression or an alteration in ICAM-1 subcellular distribution. Surprisingly, deletion of the ICAM 1 gene enhanced hemorrhagic shock-induced lung neutrophil accumulation. These results suggest that hemorrhagic shock induces preferential neutrophil accumulation to the lung that appears to occur independent of ICAM-1-expression. PMID- 11770043 TI - Gut damage during hemorrhagic shock: effects on survival of oral or enteral interleukin-6. AB - It has been reported that oral interleukin (IL)-6, without deleterious systemic side effects, prevents bacteremia and gut epithelial apoptosis after hemorrhagic shock (HS) in rodents. The goal of this study was to explore potential benefit of oral or enteral IL-6 on the gut and, consequently, on survival in a long-term outcome model of HS in rats. In Study A, 20 rats (control and IL-6, n = 10 per group) were anesthetized by spontaneous breathing of halothane and N2O. The left femoral vein and artery were cannulated. HS was initiated with withdrawal of 3 mL of blood per 100 g body weight over 15 min, and mean arterial pressure was maintained at 40 to 50 mmHg for another 75 min (total HS 90 min) by blood withdrawal or infusion of Ringer's solution. At HS 90 min, resuscitation included reinfusion of shed blood and additional Ringer's solution to restore normotension for 30 min. After awakening at resuscitation time 30 min, the rats received either 300 units IL-6 or the same volume of vehicle (controls) injected into the stomach via a feeding cannula. In Study B, 20 rats (control and IL-6, n = 10 per group), fasted overnight, were prepared and treated as in Study A, except that HS was initiated with withdrawal of 2 mL blood per 100 g over 10 min, and mean arterial pressure was maintained at 35-40 mmHg. IL-6 rats received 3,000 units IL 6 in 5 mL of normal saline injected directly into the ileum lumen 20 min after induction of shock and again at resuscitation time 60 min. Control rats received normal saline alone. In both studies, survival was observed to 72 h. In Study A, 7 of 10 rats in the control group and 5 of 10 in the IL-6 group survived to 72 h (NS). Macroscopic assessment of gut injury was not different between the two groups. In Study B, 6 of 10 rats survived to 72 h in each group. Frequency of bacteria growth in liver tissue of 72 h survivors was not different between the two groups. IL-6, administered into the stomach or directly injected into the small intestine lumen, did not protect the gut from ischemic injury, nor did it improve survival following severe HS in rats. PMID- 11770045 TI - Hemorrhage alters neuroendocrine, hemodynamic, and compartment-specific TNF responses to LPS. AB - The aim of the present study was to determine the effects of fixed pressure (40 mmHg) hemorrhage (HEM) followed by fluid resuscitation with Ringer's lactate on the subsequent hemodynamic, neurohormonal, and TNF response elicited by systemic lipopolysaccharide (LPS) administration. Chronically catheterized, conscious, unrestrained male Sprague-Dawley rats were randomized to either HEM (n = 12) or sham (n = 12) groups. HEM and sham animals were randomized to receive either LPS (100 mg/100 g body weight) or an equal volume of intravenous saline 1.5 h after completion of the resuscitation period. LPS administration produced an immediate 20% decrease in mean arterial pressure in sham animals, which was accentuated in HEM animals (40%, P < 0.05 versus sham). Moreover, HEM blunted (75%, P < 0.05) the LPS-induced increase in plasma TNF concentrations. TNF was not detected in bronchoalveolar lavage fluid (BALF) obtained from sham LPS-treated animals. In contrast, TNF levels were significantly elevated (35 +/- 17 pg/mL) in HEM LPS treated animals. A 400% increase in lung TNF content following LPS treatment was not affected by prior HEM. LPS administration produced a marked increase in plasma epinephrine, norepinephrine, and corticosterone levels in sham animals. HEM blunted the LPS-induced rise in circulating levels of epinephrine and corticosterone without altering that of norepinephrine. Our second set of studies showed that the increase in BALF TNF was associated with a 30% increase in wet-to dry lung weight ratios, suggesting that this is most likely the result of leaky endothelium following hemorrhage and LPS. Furthermore, alterations in LPS-induced alveolar macrophage TNF production following HEM were not detected. These results indicate that HEM altered the hemodynamic, neurohormonal, and circulating TNF responses to systemic LPS administration. In addition, our results suggest that HEM impaired the compartmentalization of the inflammatory response to LPS, without affecting alveolar macrophage responses to LPS. The role of altered neuroendocrine responses to a second challenge in modulating proinflammatory responses remains to be elucidated. PMID- 11770044 TI - Upregulation of intraepithelial lymphocyte (IEL) function in the small intestinal mucosa in sepsis. AB - Host defense mechanisms preventing bacterial invasion are particularly important in the gastrointestinal tract, since most gram-negative infections originate from there. Intraepithelial lymphocytes (IEL) seem to play an important role in this immune surveillance of the intestine, although their function in sepsis is not fully understood. To evaluate the characteristics of IEL in sepsis, C57BL/6 mice received a non-lethal dose of LPS and IEL were harvested at various time points thereafter. Although IEL displayed no phenotypic changes after endotoxemia, they displayed enhanced cytolytic activity and increased proliferation after LPS injection In addition, IEL from septic mice showed enhanced gamma interferon (IFN gamma) production after LPS administration. The production of IFN-gamma may have induced the increased intestinal NOS-2 mRNA expression which was observed after endotoxemia. In conclusion, endotoxemia leads to functional activation of IEL without phenotypic changes. The activation of IEL and the subsequently increased NOS-2 expression may be important mechanisms in maintaining the mucosal barrier after sublethal LPS challenge. PMID- 11770046 TI - The role of Kupffer cell inhibition in porcine endotoxemia. AB - The selective Kupffer cell inhibitor gadolinium chloride (GdCl3) has been demonstrated to protect animals from lethality in experimental endotoxemia and sepsis in rodent models. This study was designed to investigate the effect of Kupffer cell blockade on the early response to endotoxin in a large animal model. Using a porcine endotoxemia model, animals were randomized to receive either GdCl3 (10 mg/kg or 30 mg/kg; n = 8 in each group) or vehicle saline (n = 8) 24 h before exposure to endotoxin. Pretreatment with GdCl3 resulted in a dose dependent reduction in early hepatic oxygen consumption as well as oxygen extraction ratio in response to continuous infusion of endotoxin. At 5 h there was significant lower serum AST level in animals given 30 mg/kg of GdCl3 as compared to the two other groups. Pretreatment with GdCl3 induced a dose dependent reduction of Kupffer cells in the liver sinusoids. Despite this, all animals deteriorated with continuous infusion of endotoxin as evidenced by the progressive reduction in cardiac output, mean arterial pressure and total liver blood flow. Also, increases in pulmonary arterial pressure, portal venous pressure and systemic, pulmonary and hepatic vascular resistance were seen. This is consistent with activation of other cell populations and defense mechanisms by endotoxin, perpetuating the septic response. However, modulation of reticuloendothelial cell function seems feasible also in larger animals, and our results stimulate to further research on potential immunomodulatory tools in early sepsis. PMID- 11770047 TI - Prostacyclin analogue (OP-2507) induces delayed ex vivo neutrophil apoptosis and attenuates reperfusion-induced hepatic microcirculatory derangement in rats. AB - Leukocyte-endothelial adherence and changes of blood flow in microcirculation are associated with the development of ischemia-reperfusion injury in the liver. Polymorphonuclear neutrophil (PMN) apoptosis is essential to maintain homeostasis and plays a major role in limiting the reperfusion-related systemic effects. This study investigates the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Five groups were evaluated: (1) sham-operated control, n = 8; (2) ischemia control (1 h ischemia, 5-h reperfusion), n = 8; (3) intravenous infusion with OP-2507 ([15 cis-14-propylcyclohexyl]-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-ni-trilo-PGF, methyl eater) at a dose of 1 microg/kg/min plus ischemia, n = 8; (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia, n = 8, and (5) sham-operated control and intravenous infusion with OP-2507 at a dose of 1 microg/kg/min, N =8. Laser-Doppler flowmetry and an in vivo microscopy were used to investigate hepatic microcirculation. PMN apoptosis was quantitated by flow cytometric labeling of DNA strand breaks. Tissue malondialdehyde and adenosine triphosphate were determined at the end of the experiment. Compared with the ischemia control group, OP-2507 significantly improved harmful insults following ischemia-reperfusion. The changes of mean systemic arterial pressure following ischemia-reperfusion have been significantly attenuated by OP- 2507 at both doses. OP-2507 lessened adherent leukocyte count in the post-sinusoid venules, and improved flow velocity in these areas. OP-2507 at both doses reduced malondialdehyde and increased adenosine triphosphate levels and this effect was dose-related. The activity of delayed ex vivo PMN apoptosis was significantly lower in the ischemia group than that of control and treatment groups. OP-2507 induced the activity of PMN apoptosis and its effect is dose-related, also. The PMN apoptosis activity is strongly correlated with parenchymal damages. This study demonstrates that OP-2507 treatment with ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model, and increase spontaneous neutrophil apoptosis ex vivo. PMID- 11770048 TI - Cyclooxygenase-2-mediated regulation of Kupffer cell interleukin-6 production following trauma-hemorrhage and subsequent sepsis. AB - Studies indicate that trauma-hemorrhage results in activation of Kupffer cells to release inflammatory mediators and it leads to immunosuppression and increased susceptibility to subsequent sepsis. The cyclooxygenase (COX) product prostaglandin (PG) E2 appears to be central to this process, however, non selective inhibition of COX activity with non-steroidal anti-inflammatory agents that block both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase has not yielded promising results in trauma patients. Nonetheless, it remains unknown whether selective inhibition of COX-2 activity has any salutary effect following trauma-hemorrhage and subsequent induction of sepsis. To study this, male C3H/HeN mice were subjected to laparotomy (i.e., soft-tissue trauma) and hemorrhagic shock (35 +/- 5 mmHg for 90 min, then resuscitated) or to sham operation. Twenty-four hours later, the mice were subjected to sepsis by cecal ligation and puncture (CLP) or to sham CLP. The mice were treated with the COX-2 inhibitor NS-398 (10 mg/kg body weight, intraperitoneally) or vehicle immediately after trauma-hemorrhage or sham operation, 12 h thereafter, and following CLP or sham CLP. At 5 h after CLP, plasma PGE2, Interleukin-(IL) 6, and TNF-alpha levels were determined along with Kupffer cell IL-6 and TNF-alpha production in vitro. NS-398 treatment markedly suppressed the elevation in plasma PGE2 levels following CLP. The increase in plasma IL-6 levels after CLP were also significantly attenuated by NS-398 treatment. In vitro Kupffer cell IL-6 production after CLP was significantly reduced by in vivo NS-398 treatment. However, NS-398 had no effect on TNF-alpha levels, in vivo and in vitro. These findings indicate that activation of COX-2 following trauma-hemorrhage and subsequent sepsis up-regulates Kupffer cell IL-6 production. Thus, selective inhibition of COX-2 activity may reduce the deleterious consequences of sepsis under such conditions. PMID- 11770049 TI - Spared discrimination and impaired reversal eyeblink conditioning in patients with temporal lobe amnesia. AB - The effect of medial temporal lobe damage on a 2-tone delay discrimination and reversal paradigm was examined in human classical eyeblink conditioning. Eight medial temporal lobe amnesic patients and their demographically matched controls were compared. Amnesic patients were able to distinguish between 2 tones during the initial discrimination phase of the experiment almost as well as control participants. Amnesic patients were not able to reverse the previously acquired 2 tone discrimination. In contrast, the control participants showed improved discrimination performance after the reversal of the tones. These findings support the hypothesis that the hippocampus and associated temporal lobe regions play a role in eyeblink conditioning that becomes essential in more complex versions of the task, such as the reversal of an acquired 2-tone discrimination. PMID- 11770050 TI - Reactivation of hippocampal ensemble activity patterns in the aging rat. AB - In young rats, the pattern of neuronal ensemble activity correlations expressed among hippocampal pyramidal cells during behavior persists during subsequent quiet wakefulness and slow-wave sleep, a process that may facilitate the consolidation of episodic memories. The present study explored the hypothesis that age-related changes in this process might contribute to memory impairments observed during normal aging. Neuronal activity was recorded from CA1 pyramidal cells, and in both young and old rats, there was a strong similarity between the resting epoch activity patterns and those from the preceding behavior epoch. This similarity was strongest during sharp-wave events. There were no detectable differences in the reactivation process or the decay rate between the young and old age groups. Thus, age differences in spatial memory do not appear to be explainable by differences in the spontaneous reactivation of familiar patterns within the hippocampus during the immediate postbehavior period. PMID- 11770051 TI - The effect of cytotoxic lesions of the hippocampus on recognition memory in the rat: effects of stimulus size. AB - Rats with excitotoxic hippocampal lesions were trained on delayed nonmatching-to sample (DNMS) with small goal boxes, containing complex objects, presented on a pseudo trial-unique schedule. A series of experiments then tested performance on repeated presentation of either the small object or large empty goal boxes. All rats acquired the nonmatching rule, but hippocampal-lesioned rats performed less well than controls on choice accuracy for the final 2 blocks of acquisition. In the study's main phase, the lesions impaired choice accuracy when the large empty boxes were used as stimuli. This deficit was ameliorated when the rats were tested with the small object boxes, although the performance of the hippocampal lesioned rats was still below that of controls. These results extend previous reports of box size-dependent effects of hippocampal aspiration lesions on DNMS and suggest that selective damage to the hippocampus, not neuronal loss in adjacent structures or fiber tracts, is critical for the effect. PMID- 11770052 TI - Hippocampal-prefrontocortical circuits: PKA inhibition in the prefrontal cortex impairs delayed nonmatching in the radial maze in rats. AB - Recent findings implicate the prefrontal cortex (PFC) and, in particular, frontocortical dopamine acting at D1-like receptors, in working memory. However, the mechanisms underlying this function of dopamine remain unknown. The present studies evaluated the hypothesis that dopamine contributes to working memory through its action on the 2nd messenger cyclic 3',5'-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA). Thus, rats were trained to perform random foraging or delayed (30 min) nonmatching-to-position (delayed win shift) tasks on the radial maze. With hippocampal output to the frontal cortex disconnected by injecting lidocaine (20 microg/0.5 microl) unilaterally into the ventral subiculum, contralateral frontocortical injections of lidocaine (20 microg/0.5 microl) or the D1-like dopamine receptor antagonist SCH 23390 (0.5 microg/0.5 microl) impaired delayed win-shift but not random foraging, replicating previous findings. In similarly disconnected rats, frontocortical injections of the PKA inhibitor Rp-cAMPS (5.0 and 10.0, but not 1.0, microg/0.5 microl) selectively impaired delayed nonmatching-to-position. Results suggest that activation of the cAMP-PKA pathway by dopamine acting at D1-like receptors in the frontal cortex is necessary for working memory. PMID- 11770053 TI - Dissociation of the effects of bilateral lesions of the dorsal hippocampus and parietal cortex on path integration in the rat. AB - Rodents are able to rely on self-motion (idiothetic) cues and navigate toward a reference place by path integration. The authors tested the effects of dorsal hippocampal and parietal lesions in a homing task to dissociate the respective roles of the hippocampus and the parietal cortex in path integration. Hippocampal rats exhibited a strong deficit in learning the basic task. Parietal rats displayed a performance impairment as a function of the complexity of their outward paths when the food was placed at varying locations. These results suggest that the parietal cortex plays a specific role in path integration and in the processing of idiothetic information, whereas the hippocampus is involved in the calibration of space used by the path integration system. PMID- 11770054 TI - A model of hippocampal activity in trace conditioning: where's the trace? AB - The hippocampus is generally thought to play a modulating role in the timing of conditioned responses in classical trace conditioning. One hypothesis is that the hippocampus stores a memory trace of the conditioned stimulus (CS) during the stimulus-free period. Cellular recordings, however, do not show any obvious CS storage. This article examines this issue by using a biologically plausible model of the CA3 region of the hippocampus. Simulations of the model reproduce both behavioral and physiological experimental data. On the basis of neural codes that develop in the model, the authors hypothesize that the hippocampus functions as a time-indexed encoding device for the CS and not as a CS storage buffer. Specifically, the CS initiates a sequence of neural activity during the trace interval that only indirectly represents the CS. The model yields 2 predictions: Some cells will increase in activity only during the trace interval, and some unconditioned stimulus (US)-coding cells will shift in time and fire before US onset. PMID- 11770055 TI - Age-related deficits in context discrimination learning in Ts65Dn mice that model Down syndrome and Alzheimer's disease. AB - All individuals with Down syndrome (DS) eventually develop the neuropathology of Alzheimer's disease (AD), which is characterized by a premature loss of basal forebrain cholinergic neurons. Similarly, between 4 and 6 months of age, Ts65Dn mice, which model DS, lose cholinergic markers in their medial septal neurons. It is not known whether Ts65Dn mice have age-related learning deficits as well. Control and Ts65Dn mice were tested at several ages in context discrimination. Controls at all ages showed no deficits in learning this task. Ts65Dn mice younger than 3 months demonstrated impaired learning, suggesting a possible developmental delay in Ts65Dn mice. Four-month-old Ts65Dn mice showed no deficits, whereas Ts65Dn mice older than 5 months were impaired in learning the task. Therefore, Ts65Dn mice have an age-related learning impairment that coincides with their age-related neuroanatomical abnormalities and, consequently, may be a useful model of AD. PMID- 11770056 TI - Latent inhibition, but not prepulse inhibition, is reduced during withdrawal from an escalating dosage schedule of amphetamine. AB - The enhanced locomotor and stereotypic responses of the rat to repeated amphetamine (AMPH) administration are considered to be an animal model of positive schizophrenic symptoms. In contrast, behaviors observed during withdrawal from repeated AMPH are believed to model depression or anxiety. In the present study, the authors tested whether AMPH withdrawal might also elicit behaviors consistent with animal models of schizophrenia, specifically, disruptions in latent inhibition (LI) of 2-way active avoidance and prepulse inhibition (PPI) of startle. Rats treated with escalating doses of AMPH (6 days, 1-5 mg/kg ip) or saline were tested for LI and PPI during withdrawal. LI was eliminated by prior AMPH treatment in rats tested at 4, 13, and 28 days of withdrawal. In contrast, PPI did not differ between AMPH and control groups. These results support an interrelationship between repeated-AMPH and LI disruption, but not PPI-disruption, models of schizophrenia. PMID- 11770057 TI - Patterns of Fos expression in the amygdala and ventral perirhinal cortex induced by training in an olfactory fear conditioning paradigm. AB - The activation of amygdaloid nuclei, the ventral perirhinal cortex (vPRh), and several other brain areas in the rat during the acquisition and expression of olfactory fear conditioning was assessed through Fos immunocytochemistry in 3 separate experiments. The results of Experiment 1 suggest that olfactory and somatosensory inputs may functionally converge in the anterior region ot the medial nucleus (aMe). The results of Experiment 2 indicate that the aMe exhibited significantly greater Fos-like immunoreactivity (FLI) in subjects acquiring conditioned stimulus-unconditioned stimulus associations than in those presented with the same olfactory and somatosensory stimuli in a manner that precluded acquisition. The results of Experiment 3 indicate that the vPRh appeared to exhibit learning-related increases in FLI during the expression of previously acquired associations. Collectively, these data suggest that the aMe and vPRh may be critically involved in different aspects of olfactory fear conditioning. PMID- 11770058 TI - Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats. AB - Attempts to condition fear potentiation of startle (FPS) in rats younger than 23 days of age have not been successful, regardless of the type of aversively conditioned stimulus used (P. S. Hunt, R. Richardson, & B. A. Campbell, 1994; R. Richardson, G. Paxinos, & J. Lee, 2000; R. Richardson & A. Vishney, 2000). In the present study, the authors report that peripheral injections of strychnine hydrochloride, a glycine receptor antagonist, and intracerebroventricular infusions of corticotropin releasing hormone (CRH) both potentiated the acoustic startle response (ASR) in 16-18-day-old rats. Because strychnine and CRH have distinct sites of activation in the primary startle pathway, it can be concluded that this pathway is functional and modifiable in rats younger than 23 days of age. This finding suggests that the failure to observe conditioned FPS in preweanling rats is due to an immaturity of the secondary fear circuit responsible for enhancing the ASR during a fear state. PMID- 11770059 TI - Adenosine A1 receptor activation selectively impairs the acquisition of contextual fear conditioning in rats. AB - Three experiments were conducted to examine the importance of adenosine A1 receptors for the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. In Experiment 1, the selective adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA), or saline was administered intraperitoneally to male rats 30 min prior to Pavlovian fear conditioning, which consisted of 7 tone-shock pairings. Adenosine A1 receptor activation dose-dependently and selectively disrupted the acquisition of contextual fear conditioning while sparing tone-shock associations. Experiments 2 and 3 demonstrated that CPA's selective disruption of contextual learning could not be attributed to context being weaker than tone conditioning or to state dependent learning. Adenosine A1 receptor activation also impaired the expression of both context- and tone-elicited fear. These results suggest that endogenous adenosine modulates the acquisition and expression of emotional (fear) memories by acting on A1 receptors in brain regions underlying fear conditioning. PMID- 11770060 TI - Enhancement of excessive lever-pressing after post-training signal attenuation in rats by repeated administration of the D1 antagonist SCH 23390 or the D2 agonist quinpirole, but not the D1 agonist SKF 38393 or the D2 antagonist haloperidol. AB - The authors have recently shown that attenuation of an external response feedback leads to excessive lever-pressing that is not associated with attempts to collect reward, and they have suggested that this may be an analogue to "unreasonable" excessive behavior characteristic of obsessive-compulsive disorder. The present study shows that repeated administration of SCH 23390 or quinpirole, but not SKF 38393 or haloperidol, enhances this behavioral pattern. On the basis of data regarding the enduring effects of chronic treatment with dopaminergic agents, these results suggest that overstimulation of striatal D1 receptors underlies enhanced response to signal attenuation. These results may link the hypothesis that obsessions and compulsions result from a deficient response feedback mechanism with findings implicating dopaminergic abnormalities in the production of obsessions and compulsions. PMID- 11770061 TI - The morphogenesis of motor rituals in rats treated chronically with the dopamine agonist quinpirole. AB - Rats injected repeatedly with the dopamine agonist quinpirole develop motor rituals that evolve through a cascade of 4 behavioral processes. The 1st involves increased activity. The 2nd involves increased path stereotypy, reflected in traveling repeatedly along the same few paths. The 3rd is an increase in the frequency of stopping in a few places, along with a decrease in stopping in other places. The 4th is a decrease in the repetition of movements performed in the specific stopping places. Altogether, these processes culminate in stereotypy, a typical short set of movements composed of a single performance of each movement type. Thus, stereotypy arises from changes in the temporal and spatial organization, but not the content, of behavioral patterns. These results provide a model for the development of motor rituals and their linkage to normal behavior and to the physical properties of the environment. PMID- 11770062 TI - Self-administration of ethanol and saccharin in newborn rats: effects on suckling plasticity. AB - Responsiveness to a surrogate nipple providing water, saccharin, 5% ethanol, or 10% ethanol was tested in newborn rats naive to suckling (3-5 hr old) on Postnatal Day (P) 0 and in older neonates with regular suckling experience on P1 or P2. At all ages, pups demonstrated greater nipple attachment for saccharin or 5% ethanol than for water. Intake of saccharin and 5% ethanol was high in newborns, far exceeding that of water. At P1 and P2, pups exhibited a preference for saccharin, but not for 5% ethanol. Preexposure to a nipple providing ethanol or saccharin (but not a nipple alone or fluids alone) increased subsequent responsiveness toward an empty surrogate nipple (no fluid), both 1 hr and 24 hr after preexposure. Although, during preexposure, pups responded most positively to the nipple providing saccharin, the longest time spent on an empty nipple was observed in pups preexposed to 10% ethanol. PMID- 11770063 TI - Long-lasting effects of neonatal stimulation on the behavior of rats. AB - The present study aimed to analyze the effects of neonatal stimulation on species specific behaviors (defensive reactions to a predator and social interactions) in adult male and female rats. Handling and an unpredictable sequence of aversive stimuli were applied to male and female pups from the 1st to the 10th day after delivery; behavioral inhibition, aggression, and sexual behavior were evaluated in adulthood. Results showed that either neonatal handling or aversive stimulation decreased behavioral inhibition in a novel and potentially harmful situation (open field with a predator) in both male and female rats and increased maternal aggressive behavior. Sexual behavior in both males and females decreased, which could affect reproductive capability. The results could cast doubts on the generalization of beneficial effects of neonatal stimulation on the behavior of adult rats. PMID- 11770064 TI - Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus). AB - Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals. PMID- 11770065 TI - Day length and sociosexual cohabitation alter central oxytocin receptor binding in female meadow voles (Microtus pennsylvanicus). AB - In voles (Microtus), central oxytocin (OT) receptor patterns are associated with interspecific social organization. Social, monogamous voles have more OT receptors in the extended amygdala than asocial, nonmonogamous voles. Nonmonogamous meadow voles (Microtus pennsylvanicus), which exhibit seasonal changes in social organization (long day [LD] females are territorial, short day [SD] females live socially), provide a model for examining whether OT receptor patterns are associated with seasonal changes in intraspecific social behaviors. The authors examined whether sexually inexperienced (naive) SD females had more OT receptor binding than naive LD females. Naive SD females had greater OT receptor binding in the lateral septum (LS), lateral amygdala (LatAmyg), and central amygdala (CenAmyg) than less social, naive LD females. Because both SD and LD females acquire partner preferences, the authors assessed whether OT receptor binding was associated with partner preference onset. For LD females, partner preference onset corresponded with greater OT receptor binding in the anterior olfactory nucleus, LS, and bed nucleus of the stria terminalis, compared with naive LD females. In contrast, naive SD females and those exhibiting partner preferences did not differ. However, SD females that failed to acquire partner preferences showed less OT binding in the LatAmyg and CenAmyg. This study is the first to show that central OT receptor patterns are associated with seasonal changes in intraspecific social organization and partner preference onset in a nonmonogamous rodent. PMID- 11770066 TI - Excitotoxic lesions of the hippocampus leave sensory preconditioning intact: implications for models of hippocampal function. AB - Learning about contextual cues is markedly disrupted in rats with hippocampal lesions. One analysis of this disruption is that it reflects a general failure to form associations between the elements of complex events. A straightforward prediction of this analysis is that sensory preconditioning will be disrupted by hippocampal lesions. This prediction was assessed by presenting rats with flavored solutions composed of 2 elements (A and X) before X was paired with an injection of the emetic, lithium chloride. A subsequent test revealed that rats were less willing to consume Solution A than they were to consume a control solution, B. This was true of rats with sham lesions and those with excitotoxic lesions of hippocampus. These findings fail to support the proposition that the hippocampus-dependent deficit in contextual conditioning is due to a general disruption to the process of associating the elements of complex events. PMID- 11770067 TI - Naloxone blocks place preference conditioning after paced mating in female rats. AB - Sexual behavior in male rats induces a positive affect as evaluated by conditioned place preference (CPP). In addition, when females control or "pace" the rate of sexual interaction, a clear CPP is also observed. The reward state induced by mating in male rats is blocked by the injection of the opioid antagonist naloxone. In the present experiment, a dose of 4 mg/kg of naloxone completely blocked the CPP induced in females by paced mating. It appears that a common opioid system is involved in the positive affect induced by sexual behavior in both male and female rats. PMID- 11770068 TI - The heterogeneities of the heart. PMID- 11770069 TI - Electrical heterogeneity within the ventricular wall. AB - Recent studies have established the presence of three distinct cell types in the ventricular myocardium: epicardial, M and endocardial cells. Epicardial and M cell action potentials differ from endocardial cells with respect to the morphology of phase 1. These cells possess a prominent transient outward current (I(to))-mediated notch responsible for the 'spike and dome' morphology of the epicardial and M cell response. M cells are distinguished from the other cell types in that they display a smaller slowly activating delayed rectifier current (I(Ks)), but a larger late sodium current (late I(Na)) and sodium-calcium exchange current (I(Na-Ca)). These ionic distinctions underlie the longer action potential duration (APD) and steeper APD-rate relationship of the M cell, which is more pronounced in the presence of antiarrhythmic agents with class III actions. The preferential prolongation of the M cell action potential results in the development of a transmural dispersion of repolarization (TDR), which can be estimated from the electrocardiogram (ECG) as the interval between the peak and the end of the T wave (QTpeak-QTend interval). Using the canine arterially perfused ventricular wedge model, transmembrane action potentials of the various cardiac cell types can be correlated to the waveforms of the ECG, providing insight into the cellular etiology of ECG abnormalities. Two congenital syndromes of sudden cardiac death that have been modeled using this technique are the long QT and Brugada syndromes. The long QT syndrome has been linked to 5 gene mutations on chromosomes 3, 7, 11, and 21. Mutations in the cardiac sodium channel SCN5A have been linked to families with a history of the Brugada syndrome. Although the etiologies of these two syndromes are different, lethal arrhythmias in both are thought to arise due to amplification of intrinsic electrical heterogeneities. Similar mechanisms are likely responsible for life threatening arrhythmias in a variety of other cardiomyopathies ranging from heart failure and hypertrophy, which involve mechanisms similar to those operative in LQTS, to ischemia and infarction, which may involve mechanisms more closely resembling those responsible for the Brugada syndrome. PMID- 11770070 TI - Presence, distribution and physiological function of adrenergic and muscarinic receptor subtypes in the human heart. AB - The sympathetic and parasympathetic nervous system play a powerful role in controlling cardiac function by activating adrenergic and muscarinic receptors. In the human heart there exist alpha1-, beta1- and beta2-adrenoceptors and M2 muscarinic receptors and possibly also (prejunctional) alpha2-adrenoceptors. Beta1- and beta2-adrenoceptors are quite evenly distributed in the human heart while M2-receptors are heterogeneously distributed (more receptors in atria than in ventricles). Stimulation of beta1- and beta2-adrenoceptors causes increases in heart rate and force of contraction while stimulation of M2-receptors decreases heart rate (directly in atria) and force of contraction (indirectly in ventricles). Pathological situations (such as heart failure) or pharmacological interventions (for example, beta-blocker treatment) can alter the distribution of beta1- and beta2-adrenoceptors in the human heart, while M2-receptors are only marginally affected. On the other hand, relatively little is known on distribution and functional role of alpha1- and alpha2-adrenoceptor subtypes in the human heart. PMID- 11770071 TI - How heterogeneous is the cardiac autonomic innervation? AB - The rich autonomic innervation of the heart plays an important role in modifying cardiovascular function. Recently developed in vivo scintigraphic imaging techniques allow for visualization of the autonomic innervation of the heart. Studies using the modalities have shown heterogeneity of sympathetic innervation in various kinds of pathological conditions as well as normal human heart. The inferioposterior region shows typically less sympathetic innervation than the anterior region. In addition, neuropathic processes appear to commence in inferior-apical regions extending towards the base of the heart. Arrhythmogeneity has been related to the heterogeneous innervation of the heart and heterogeneous uptake of radiolabeled catecholamine analogues, such as I-123 metaiodobenzylguanidine, can be found in patients with arrhythmia. In dilated cardiomyopathy, reduced uptake indicates a poor prognosis which allows risk stratification for patients with heart failure. Heterogeneity of the reinnervation process following heart transplantation has also been investigated. Evidence was found of reinnervation primarily in the basal anterioseptal region and to a lesser degree in the inferioposterior and apical regions. Tracer approaches are uniquely suited to identify regionally altered innervation and provide tools for linking information on cardiac autonomic innervation with other clinical aspects. PMID- 11770072 TI - Microheterogeneity of myocardial blood flow. AB - Myocardial blood flow exhibits the most marked heterogeneity at the microvascular level. Its within-layer spatial distribution can be described from subepi- to subendocardium with resolutions of 0.1 x 0.1 to 1 x 1 mm2 by quantitative digital radiography based on the technique of desmethylimipramine deposition. In the subendocardium, flow heterogeneity is the highest, whereas local flow randomness is the lowest, showing the clustered pattern of high- or low-flow regions. The resolution-dependence of flow heterogeneity is characterized by its fractality, which holds consistently down to the microvascular level through the vascular structural transition from the treelike arteriolar to the non-treelike capillary network. Flow heterogeneity is adjustable in a transmurally different manner to local metabolic changes. The redistribution of flow is considered as a result of adaptive coordination of microperfusion between adjacent microcirculatory units, which are perfused by a single precapillary arteriole. PMID- 11770073 TI - Temporal fluctuations of myocardia high-energy phosphate metabolite with the cardiac cycle. AB - This review describes the temporal changes of high-energy phosphate metabolites during the cardiac cycle. Under baseline condition, the extent of cyclical changes ("cycling") of ATP, phosphocreatine and inorganic phosphate varies between 10-15%. Such energy oscillations are not augmented under various forms of metabolic stress including 1) inotropic stimulation, 2) acute hypoxia and 3) failing, chronically infarcted hearts. Thus, the concentrations of high-energy phosphates over the cardiac cycle are a tightly regulated entity, even when energetic needs are substantially augmented. PMID- 11770074 TI - Correlation between heterogeneous myocardial flow and oxidative metabolism in normoxic and stunned myocardium. AB - Myocardial blood flow exhibits considerable heterogeneity. Consequently, oxygen supply to the myocardium is also heterogeneous, as is myocardial metabolism. Many lines of evidence show a close correlation between local flow and local metabolism in the normoxic myocardium. So far, myocardial metabolism has predominantly been assessed indirectly by using labeled substrates. We used the (18)O isotope, permitting analytical separation of H2(18)O from the (18)O isotope, as well as quantification of regional oxidative metabolism by measuring the tissue residue of oxidation water in the rabbit myocardium. Correlation of local flow with oxidative metabolism was significant in the normoxic myocardium. This correlation was lost in the postischemic/reperfused myocardium. Apart from the established mechanisms underlying myocardial stunning, a mismatch between local flow and oxidative metabolism might thus also contribute to the postischemic dysfunction. In the normoxic myocardium, function should correlate with metabolism and blood flow. For technical reasons, function has not been assessed on a very local scale. Nevertheless, some considerations are presented on the heterogeneity of function as well as on the scale on which heterogeneity should be investigated to convey physiologically meaningful information on regulatory cardiac mechanisms. PMID- 11770075 TI - Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow. AB - It is well established that myocardial blood flow is heterogeneous on the local level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studies have been performed: enzyme activity and tissue metabolite level assessments. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated Vmax values, local substrate affinity (Km values) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable insight has been obtained concerning flow-metabolism matching from tissue metabolite measurements, especially when connected with mathematical model analyses. The latter permitted the calculation of metabolic flux rates (e.g., production of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologically meaningful local metabolite concentrations (e.g., free cytosolic adenosine). The bottom line of the studies reported to date is that the broad range of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenergic stimulation. Thus, high flow samples exhibit a higher oxidative metabolism than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The importance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the myocardium under control conditions, i.e., the local level of flow-metabolism matching. PMID- 11770076 TI - Assessing heterogeneous distribution of blood flow and metabolism in the heart. AB - The literature is reviewed on methods to assess heterogeneity of blood flow, substrate uptake and oxidative end energy metabolism in the normal heart, and their interrelations. Even though the factors controlling matching on the regional level remain largely obscure, the evidence that heterogeneous blood flow partially correlates to indicators of metabolism in the normal heart is accumulating, particularly in face of a correlation between acetate metabolism indicative of regional O2 consumption to microsphere blood flow. Moreover, the partial matching cannot be explained by vascular anatomical differences from one region to the other, since, although fractal theory can partially describe the branching patterns of the coronaries, vasodilation is similar among regions upon metabolic stimulation of the heart. It is dissimilar among regions, so that blood flow is redistributed, upon maximum vasodilation with adenosine or hypoxia, denoting regionally different maximum vessel diameter and flow reserve. However, regionally differing tissue composition could also contribute somewhat to regional differences in (the need for) blood flow. It is still unknown, because of technical limitations, how the foregoing measures relate to regional work load. PMID- 11770078 TI - Doppler myocardial imaging. A new tool to assess regional inhomogeneity in cardiac function. AB - In echocardiography, there is still a need for a better tool to quantify regional myocardial function. Doppler myocardial imaging (DMI) allows the calculation of local myocardial velocity profiles for segmental motion in both the radial and longitudinal direction. From the local velocity profile data, 1-dimensional regional myocardial strain rates (SR) and strain (epsilon) can now be calculated. These new deformation indices more accurately define regional function compared to velocities as they are independent of overall heart motion. This paper will define the normal segmental velocity, SR and epsilon profiles and their relationship with global mechanical event markers. It will also define the changes in local velocity and deformation characteristics, which are induced by disease and the current experimental and clinical status of this new quantitative ultrasound tool. PMID- 11770079 TI - Molecular genetics of G proteins and atherosclerosis risk. AB - Using a classical candidate gene approach, we have described a common C825T polymorphism in the gene GNB3 which encodes the ubiquitously expressed beta3 subunit of heterotrimeric G proteins. The 825T allele is associated with alternative splicing of the gene and the formation of a truncated but functionally active beta3 subunit which is referred to as Gbeta3s. Expression of the splice variant results in an enhanced G protein activation on stimulation of G protein-coupled receptors. Carriers of the 825T allele show an increased risk for hypertension and left ventricular hypertrophy. Homo- and heterozygous 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic than homozygous 825C allele carriers. Moreover, 825T allele carriers appear to have an increased risk for obesity which appears sensible given the established role of G protein signaling in adipogenesis. The highest frequencies of the 825T allele are found in ethnicities with the highest lifestyle-dependent risk for obesity, e.g., black Africans and East Asians. This suggests that the 825T allele fulfills the criteria of a thrifty genotype. PMID- 11770077 TI - The mechanical and metabolic basis of myocardial blood flow heterogeneity. AB - Precise measurements of regional myocardial blood flow heterogeneity had to be developed before one could seek causation for the heterogeneity. Deposition techniques (particles or molecular microspheres) are the most precise, but imaging techniques have begun to provide high enough resolution to allow in vivo studies. Assigning causation has been difficult. There is no apparent association with the regional concentrations of energy-related enzymes or substrates, but these are measures of status, not of metabolism. There is statistical correlation between flow and regional substrate uptake and utilization. Attribution of regional flow variation to vascular anatomy or to vasomotor control appears not to be causative on a long-term basis. The closest relationships appear to be with mechanical function, but one cannot say for sure whether this is related to ATP hydrolysis at the crossbridge or associated metabolic reactions such as calcium uptake by the sarcoplasmic reticulum. PMID- 11770080 TI - Glycolysis protects sarcolemmal membrane integrity during total ischemia in the rat heart. AB - Experimental evidence indicates that ischemic glycolysis improves myocardial tolerance to low flow ischemia and anoxia, and cellular membrane disruption signals and/or causes transition to irreversible ischemic injury. The objective of this study was to determine the impact of ischemic glycolysis on membrane integrity and myocardial viability during total ischemia. Phosphorus metabolites were measured by 31P NMR spectroscopy and cellular volumes were determined by 1H and 59Co NMR in conjunction with the extracellular marker cobalticyanide. Isolated rat hearts were submitted to 30 min of total ischemia, followed by 30 min of reperfusion. Glycogen contents were modulated by pre-ischemic perfusion with various substrates. Increased glycolytic activities, as determined from lactate production, delayed onset of ischemic contracture (p < 0.05), induced cytosolic acidification (p < 0.005) and cellular swelling during ischemia (p < 0.05), reduced post-ischemic diastolic tone (p < 0.05), improved recovery of high energy phosphates and contraction force (p < 0.005). Inhibition of glycolysis with iodoacetate and glycogen depletion with 2-deoxyglycose resulted in early onset of ischemic contracture (p < 0.005), elevated post-ischemic diastolic pressures (p < 0.05), reduced coronary flow rates and mechanical activities (p < 0.05). Cellular viability was evaluated by creatine kinase efflux, and membrane integrity was determined from cellular swelling during perfusion with hypoosmotic medium. High activities of ischemic glycolysis correlated with improved cellular viability and preserved membrane integrity, while low glycolytic fluxes were associated with membrane permeabilization (p < 0.05). The protective effect of ischemic glycolysis over sarcolemmal integrity was attributed to continuous provision of energy, undetected by 31P NMR spectroscopy. There was no evidence that ischemic swelling caused by glycolytic end-metabolites accumulation had detrimental consequences, and of excessive swelling during reperfusion. It is concluded that one of the cardio-protective mechanisms of ischemic glycolysis is energy-dependent preservation of sarcolemmal integrity and cellular viability. PMID- 11770081 TI - Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes. AB - Rat cardiomyocytes were exposed to H2O2 (1-100 micromol/L) for 10 min with washout for 10 min. Intracellular Ca2+ concentration ([Ca2+]i) was measured using fluo-3. [Ca2+]i increased with 100 micromol/L H2O2 and further increased during washout, causing irreversible contracture in one-half of the cells. The increase in [Ca2+]i with 10 micromol/L H2O2 was modest with few cells showing irreversible contracture and attenuated by caffeine, and [Ca2+]i gradually decreased during washout and this decrease was accelerated by a calcium-free solution, while 1 micromol/L H2O2 did not have any effects on [Ca2+]i or cell viability. Ca2+ overload caused during exposure to 100 micromol/L H2O2 was attenuated by caffeine with improved cellular viability but not by chelerythrine, KB-R7943 or nifedipine. With 100 micromol/L H2O2 calcium-free solution attenuated the increase during exposure and washout while KB-R7943 or chelerythrine partly attenuated further increase during washout but not improved cell viability, but chelerythrine did not have additional effect on calcium-free treatment. Catalase abolished the effects of H2O2. We concluded that the increased [Ca2+]i during exposure to 100 micromol/L H2O2 was caused both by release of Ca2+ from the intracellular store sites including the sarcoplasmic reticulum and by influx through route(s) other than the voltage-dependent Ca2+ channels or Na+/Ca2+ exchanger, although the Na+/Ca2+ exchanger or protein kinase C-mediated mechanism was partly responsible for a further increase during washout. PMID- 11770082 TI - Recombinant Sindbis virus allows expression and precise targeting of proteins of the contractile apparatus in cultured cardiomyocytes. AB - Expression of epitope-tagged sarcomeric proteins in cardiomyocytes is a powerful approach for the characterization of interacting domains. Here, we report a new strategy for the study of the targeting of contractile proteins in cardiomyocytes by Sindbis virus (SIN)-mediated gene transfer. Two recombinant SIN were generated, one encoding the myosin-light chain MLC3f-eGFP fusion protein (SINrep5/MLC3f-eGFP), and the other encoding the alpha-actinin-DsRed fusion protein (SINrep5/alpha-actinin-DsRed). After infection of long-term cultured neonatal and adult rat cardiomyocytes with SINrep5/MLC3f-eGFP, the exogenous MLC3f-eGFP fusion protein localized to the sarcomeres. Freshly isolated rod shaped ventricular cardiomyocytes infected with SINrep5/alpha-actinin-DsRed exhibited a correct incorporation of the newly synthesized alpha-actinin-DsRed fusion protein at the Z-band of the sarcomere. This allows the assumption that the exogenous protein is assembled into myofibrils in living cardiomyocy-tes using the same molecular interactions equally to the endogenous counterpart. It has been thus demonstrated that the SIN expression system makes possible the straightforward analysis of the localization of sarcomeric proteins in cultured cardiomyocytes and may offer new possibilities for the characterization of mutant proteins involved in hypertrophic cardiomyopathies. PMID- 11770083 TI - Structure and expression of the mouse cardiac calsequestrin gene. AB - Calsequestrin is a sarcoplasmic reticulum protein, which plays a predominant role in diastolic Ca2+-storage in the mammalian heart. The present study was designed to define the gene structure, developmental and tissue specific expression of the murine, cardiac isoform of calsequestrin. Two sets of genomic libraries (lambda phage and PAC) were screened using the mouse cardiac calsequestrin cDNA, and several overlapping clones were isolated. These clones were characterized using restriction enzyme digestion, Southern blotting and partial sequencing. The cardiac calsequestrin gene consists of 11 exons and its 5' flanking region is characterized by the presence of a TATA-like box, muscle specific promoter elements such as 7 E-boxes, 1 MEF-2, 1 MCBF and 1 Repeat (musS) motifs, as well as several muscle non-specific transcriptional elements (AP-2A, NRE1, NRE2, p53, Spel and TFI-IIA). Expression of the cardiac isoform of calsequestrin was first detected on day 11 pre-birth and approached adult levels by day 4 post-birth. Expression of cardiac calsequestrin was also detected in adult fast-twitch skeletal muscle, thyroid, testis and epididymis tissues. This genomic characterization of cardiac calsequestrin may form the basis for further evaluation of its regulatory role in Ca2+ homeostasis and contractility in the murine heart. PMID- 11770084 TI - Single sodium channels from human ventricular muscle in planar lipid bilayers. AB - Sodium channels from human ventricular muscle membrane vesicles were incorporated into planar lipid bilayers and the steady-state behavior of single sodium channels were examined in the presence of batrachotoxin. In symmetrical 500 mM NaCl the averaged single channel conductance was 24.7 +/- 1.3 pS and the channel fractional open time was 0.85 +/- 0.04. The activation midpoint potential was 99.5 +/- 3.1 mV. Extracellular tetrodotoxin blocked the channel with a k(1/2) of 414 nM at 0 mV. In 7 out of 13 experiments subconductance states were observed (9.2 +/- 1.2 pS). When sodium chloride concentration was lowered to 100 mM, single channel conductance decreased to 19.0 +/- 0.9 pS, steady-state activation shifted by -17.3 +/- 5.1 mV, tetrodotoxin sensitivity increased to 324 nM, and sub-conductance states were invariably observed in single channel records (7.9 +/ 0.7 pS). In the planar lipid bilayer system the properties of cardiac sodium channels from different species are not very different, but there are significant differences between sodium channels from human heart and from human CNS. PMID- 11770085 TI - Intracellular mechanisms of cGMP-mediated regulation of myocardial contraction. AB - The intracellular mechanisms of cGMP, a major intracellular mediator of nitric oxide that regulates the contractility of cardiac muscle, are still to some extent unknown. To investigate these mechanisms, we observed the effects of 8 bromo-cyclic GMP (8br-cGMP) on myofibrillar Ca2+ sensitivity and Ca2+ handling of the sarcoplasmic reticulum (SR) using beta-escin-skinned preparations from Wistar rat hearts. Both low (1 microM) and high doses (100 microM) of 8br-cGMP significantly decreased the myofibrillar Ca2+ sensitivity obtained from pCa tension relationships to a similar extent (pCa50; from 6.04 to 5.95 by 1 microM 8br-cGMP and 6.00 to 5.89 by 100 microM 8br-cGMP, respectively, n = 9 each). Whereas this Ca2+ desensitization induced by 100 microM 8br-cGMP was blocked by 1 microM KT5823, a specific inhibitor of cGMP-dependent protein kinase (PKG), not induced by 1 microM 8br-cGMP was not effected by KT5823. When the amount of Ca2+ released from the SR was estimated by the peak amplitude of 25 mM caffeine induced contractions after constant Ca2+-loading by pCa 6, both doses of 8br-cGMP significantly augmented the caffeine-induced peak force to a similar extent (125 +/- 5.8% by 1 microM 8br-cGMP and 116 +/- 5.1% by 100 microM 8br-cGMP, respectively, n = 6 each). The two observed effects of cGMP (a decrease in myofibrillar Ca2+ sensitivity and an increase in Ca2+ uptake by the SR) may participate in regulating myocardial contraction via nitric oxide. Low and high doses of cGMP seem to work mainly via PKG-independent and PKG-dependent pathways, respectively. PMID- 11770086 TI - Myocardial enzymatic activity of renin and cathepsin D before and after bilateral nephrectomy. AB - A local renin-angiotensin system is present within the myocardium and can play a role in the initiation and maintenance of cardiac hypertrophy. The source of myocardial renin maybe direct cardiac renin gene expression, or plasma renin of renal origin. A primary indication that myocardial renin is derived from plasma renin of renal origin was from work showing that cardiac renin activity was no longer detected 30 hours after bilateral nephrectomy (BNX). However, more recent studies have been able to detect myocardial renin after BNX. We measured normal rat cardiac renin before and after 48-hour BNX using a myocardial renin assay with improved sensitivity. The myocardial renin assay was also used to assess normal rat cardiac myocyte renin levels. Since cardiac tissue contains cathepsin D, a lysosomal enzyme capable of renin-like activity, a rat cathepsin D assay was also developed to assess cathepsin D contribution to renin-like activity. Several artifacts were shown to contribute to myocardial renin-like enzymatic activity levels after BNX, including initial plasma renin stimulation during BNX surgery, assay pH, and cardiac cathepsin D activity. Myocardial renin concentration after 48-BNX was found to be only approximately 1% of normal control levels, and renin concentration in normal cardiac myocytes was only 2-fold greater than assay blanks. Both results were probably overestimated due to cathepsin D contamination. In conclusion, no evidence was found for myocardial renin synthesis in the normal adult rat heart, and myocardial renin decays to near zero levels after 48-hour BNX. PMID- 11770087 TI - The evolution of vehicular trauma, 1980-2001. PMID- 11770088 TI - Avulsion fracture of the apophysis of the ischial tuberosity. PMID- 11770089 TI - The partial pelvic replacement cup in severe acetabular defects. AB - Severe bone loss resulting in pelvic discontinuity may result in <50% coverage of the socket by native bone. The goal in these cases is to bridge the gap by using bone grafts, methylmethacrylate, or both. The partial pelvis cup helps protect bone grafts during their incorporation and also provides a stable construct to the acetabulum for weight bearing. PMID- 11770090 TI - Indomethacin versus radiation therapy for heterotopic ossification after hip arthroplasty. AB - This study compared the efficacy and cost of radiation therapy with indomethacin in the prophylaxis of heterotopic ossification following total hip replacement. Twenty-two patients received a radiation dose of 10 Gy in five fractions, 28 patients 8 Gy in one fraction, and 27 patients 25 mg oral indomethacin three times a day for either 7 or 21 days. Patients at higher risk for heterotopic ossification were more likely to receive radiation therapy than indomethacin. At a mean follow-up of 2 years, there were no differences in failure rates between the high-risk patients treated with radiation and the low-risk patients treated with indomethacin. Currently, the patient-billed cost of radiation is $1400 whereas the cost for indomethacin is approximately $100. Indomethacin appears to be as effective as radiation therapy in patients at low to moderate risk for heterotopic ossification and offers significant cost savings. PMID- 11770091 TI - Results of the anatomic cementless prosthesis with different types of hydroxyapatite coating. AB - This study evaluates the clinical and radiographic results and the bone-implant osteointegration obtained with the Anatomic (Zimmer, Warsaw, Ind) cementless total hip prosthesis using three different types of surface coating. Two hundred twenty-seven patients underwent total hip arthroplasty using the Anatomic prosthesis. Patients were divided into groups based on the type of surface coating: in group A (69 patients), prostheses were uncoated; in group B (90 patients), the metaphyseal region of the prostheses was coated with calcicoat (a mixture of hydroxyapatite and tricalcium phosphate) (Zimmer); and in group C (68 patients), the fiber mesh and proximal stem of the prostheses were coated with calcicoat. Prostheses coated with calcicoat yielded better clinical and radiographic results than uncoated prostheses, especially in regard to thigh pain. No significant difference was observed between groups B and C. These results obtained with the Anatomic prosthesis are promising and encourage the use of implants coated with calcicoat. PMID- 11770092 TI - A 4- to 10-year follow-up study of the Tricon-M noncemented total knee replacement. AB - This study reviews the clinical and radiographic results of 207 consecutive noncemented Tricon-M (Smith & Nephew Inc, Memphis, Tenn) total knee replacements (TKRs) in 189 patients. The patella was surfaced in 119 cases, and mean follow-up was 8 years (range: 4-10 years). At final follow-up, mean Hospital for Special Surgery score improved 45 points in 187 cases. Survivorship, with failure defined as the need for revision, was 98% at 4 years, 97% at 7 years, 94% at 8 years, and 90% at 10 years. Twenty-one (11.3%) patients went on to revision. Results for overweight and obese patients did not differ significantly from normal-weight patients. The noncemented Tricon-M TKR prosthesis yields acceptable results; however, patella surfacing and the use of a tibial polyethylene insert > or = 12 mm thick are recommended. PMID- 11770093 TI - Comparison of interactive voice response and written self-administered patient surveys for clinical research. AB - This study compared the use of an interactive voice response (IVR) system with a written survey to collect data. Consecutive patients seen in an orthopedic clinic completed the Short Musculoskeletal Function Assessment (SMFA) by either IVR or written questionnaire and then were asked to complete the form again 3-7 days later using the opposite modality. Patient response rates were analyzed for differences between the self-administered IVR and written modes of administration. Three orthopedic clinics participated in the study. No significant differences between method of administration or individual differences in response per patient were found. Therefore, no significant differences in measurement are found when IVR is compared to the written SMFA. PMID- 11770094 TI - Effectiveness of suction drainage after primary or revision total hip and total knee arthroplasty. AB - Postoperative suction drainage of a surgical wound is aimed at evacuation of wound hematoma. This study evaluated the effectiveness of suction drainage in joint replacement surgery. Surgical wounds in 206 patients with primary or revision hip and knee arthroplasty were assessed according to a set criteria. Forty-eight hours postoperatively, wound hematoma and exudate formation were not related to the use of suction drains. A greater tendency of wound oozing was seen in revision hip arthroplasty performed with postoperative suction drainage. Therefore, postoperative suction drainage did not affect hematoma formation or wound oozing and is thus considered an unnecessary practice. PMID- 11770095 TI - Traumatic combined radial and ulnar axial wrist dislocation. AB - In axial wrist dislocation, the proximal and distal transverse arches are disrupted and the carpus and metacarpal bases are split longitudinally. Early reduction and stabilization of the dislocation combined with exploration and decompression provide the best results. PMID- 11770096 TI - Bilateral hip dislocations in a father and son with Ehlers-Danlos syndrome. PMID- 11770097 TI - Giant-cell tumor of the patellar tendon. PMID- 11770098 TI - Clavicle fracture and posterior sternoclavicular dislocation in a newborn. PMID- 11770099 TI - Adult isthmic spondylolisthesis. PMID- 11770100 TI - Proceedings of an international workshop held at the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 10-11 November 2000. PMID- 11770101 TI - Lipophosphoglycan of the protozoan parasite Leishmania: stage- and species specific importance for colonization of the sandfly vector, transmission and virulence to mammals. AB - Leishmaniasis is a major health problem to the human population of the tropics, subtropics and Mediterranean regions. This disease is caused by the parasitic protozoa Leishmania, which have adapted to survive in several hostile environments such as the vector insect midgut, blood and the mammalian macrophage phagolysosome. Several Leishmania glycoconjugates have been implicated as key molecules for these remarkable capabilities. This review summarizes the current knowledge on potential and proven functions of the most prominent of the Leishmania glycoconjugates, the lipophosphoglycan. PMID- 11770102 TI - Homologues of LMPK, a mitogen-activated protein kinase from Leishmania mexicana, in different Leishmania species. AB - LMPK, a mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana, is essential for the proliferation of the amastigote, the mammalian stage of the protozoan parasite. This has been demonstrated using deletion mutant promastigotes, the insect stage of the parasite: first, in vitro after differentiation to amastigotes, which subsequently lost their potential to proliferate; second, by infection of peritoneal macrophages, which were able to cope with the infection and cleared the parasites; third, by infection of BALB/c mice, which showed no lesion development. The lmpk deletion mutant promastigotes are a potential live vaccine because they infect macrophages, transform to amastigotes and deliver amastigote antigens to raise an immune response without causing the disease. In addition, inhibition of LMPK in a wild-type infection is likely to resolve the disease and as such, is an ideal target for drug development against leishmaniasis. Here we investigated the presence and copy number of lmpk homologues in Leishmania amazonensis, L. major, L. tropica, L. aethiopica, L. donovani, L. infantum, and L. braziliensis and discuss the results with regard to drug development and vaccination using kinase deletion mutants. PMID- 11770103 TI - Post transcriptional control of gene expression in Leishmania. AB - Leishmania parasites are ancient eukaryotes, characterized by unusual molecular mechanisms. We have used the gene encoding for Hsp83 as a model system for studying regulatory mechanisms that control developmental gene regulation. We previously showed that protein coding genes are regulated exclusively by post transcriptional mechanisms, while no transcriptional activation could be observed even for the conserved Hsp83 gene. We now show that processing and maturation of the Hsp83 polycistronic primary transcripts is more efficient at elevated temperatures. The mature transcripts are more stable during heat shock, with regulation conferred by 3' UTRs. Poly(A) tails of Hsp83 are approximately 30 nucleotides long, as common for other low eukaryotes. The mechanism that signals differential degradation is still unclear, since it was not possible to detect differences in deadenylation of Hsp83 transcripts at varying temperatures. Heat shock transcripts are preferentially translated at 33-37 degrees C, but unlike Drosophila, translational regulation is controlled by a region within the 3' UTR. Using this traditionally conserved system emphasizes that regulatory mechanisms in Leishmania differ from those prevailing in other eukaryotes. PMID- 11770104 TI - The heat shock protein 90 of Leishmania donovani. AB - The 90-kDa heat shock protein (Hsp90) of Leishmania donovani is a highly abundant cytoplasmic protein and is involved in a variety of cellular processes. Pharmacological deactivation of Hsp90 leads to growth arrest and induces the synthesis of heat shock proteins. Moreover, treatment of promastigote parasites with Hsp90 inhibitors induces the synthesis of amastigote-specific marker proteins and a morphological alteration similar to axenic amastigote differentiation. We propose a role for Hsp90 in the feedback control of the cellular stress response and in the control of the parasite's life cycle. PMID- 11770105 TI - Leishmaniases--their relationships to monoxenous and dixenous trypanosomatids. PMID- 11770106 TI - Comparative proteome analysis of Leishmania donovani at different stages of transformation from promastigotes to amastigotes. AB - To pass through its life cycle, protozoan parasites of the genus Leishmania have to differentiate from promastigotes to amastigotes. The molecular basis underiving this major transformation is poorly understood. One way to study this phenomenon is to isolate and characterize proteins that are specifically expressed in one of the two stages of the life cycle or during the stage differentiation. Using two-dimensional gel electrophoresis, we mapped the Leishmania donovani proteome during stage differentiation to identify stage specific proteins and regulons. A protocol for extracting proteins of both promastigote and amastigote L. donovani cells was developed, which is compatible with isoelectric focusing. Up to 400 L. donovani protein spots were visualized on a silver-stained gel. Metabolic labeling of the cells was used to compare directly the protein synthesis pattern with the protein level pattern. The silver stained images of L. donovani cells harvested on different days of stage differentiation were compared to the corresponding autoradiographs. A marked decrease in protein synthesis during stage differentiation from promastigotes to amastigotes was observed. The stained protein pattern as well as the protein pattern on the autoradiograph changed dramatically, especially after day 3 (about 24 h after pH shift) of transformation. PMID- 11770107 TI - Leishmania infection and virulence. AB - Leishmaniasis is among the most important infectious diseases of the developing world. With the advent of effective culture conditions for the various stages of the life cycle, together with state of the art biochemical, genomics, and reverse genetic approaches, it has been possible to identify virulence factors required for the infection process. Several of these virulence factors are discussed within including lipophosphoglygan, A2, cysteine proteinases, and gp63. PMID- 11770108 TI - Use of genetic complementation to identify gene(s) which specify species-specific organ tropism of Leishmania. AB - We have employed a genetic complementation screening to identify genetic markers of heat stress tolerance and visceralisation of Leishmania infection. Leishmania major, which has a low thermotolerance and which causes cutaneous lesions, was transfected with a cosmid library of L. donovani DNA. The recombinant parasites were then screened either for thermotolerance or selected by repeated passage in BALB/c mice. Cosmids which conferred selective advantage were isolated. Several strategies were tested to identify the gene(s) within the cosmids responsible for the observed selective advantages. Of the approaches tested, the complete sequence analysis of the cosmids and subsequent screening of defined candidate ORFs proved to be the method of choice. Other approaches, such as creation of sub libraries or transposon insertion strategies proved to be unsuccessful. PMID- 11770109 TI - Heat shock protein 100 and the amastigote stage-specific A2 proteins of Leishmania donovani. AB - HSP100 protein in Leishmania spp. plays an important role for the survival and integrity of intracellular amastigotes. The A2 proteins of L. donovani are functionally linked to HSP100. There is evidence for an interdependence between these two proteins, which are both expressed predominantly in the amastigote stage of Leishmania donovani. Mutant strains lacking either of these proteins display very similar phenotypes, i.e. loss of virulence both in vivo and in vitro. Also, both proteins colocalise specifically to small foci within the cytoplasm of amastigotes. PMID- 11770110 TI - The biological function of sand fly and Leishmania glycosidases. AB - This is a summary of the recent work on some glycosidases of sand flies and their Leishmania parasites. Glycosidases catalyze the hydrolysis of complex sugar subunits of polysaccharides into simple sugars. Leishmania major parasites secrete chitinase and N-acetylglucosaminase, which enables them to survive in the gut of the sand fly and are important in facilitating their transmission by the phlebotomine sand fly Phlebotomus papatasi. These enzymes are found in a wide range of trypanosomatids and the gene locus is highly conserved. The sand flies feed on plants and the ingested tissues may contain cellulose particles that the sand flies are unable to digest. Cellulolytic enzymes are secreted by L. major promastigotes and this may help to break down cellulose in infected flies and sustain their growth. Starch is a main photosynthesis product that is stored in leaves. Starch grains have been found in the midguts of field caught sand flies and alpha-amylase, the specific enzyme for starch, has been found in the salivary glands and other organs of Lutzomyia longipalpis and P. papatasi. Alpha-amylase and alpha-glucosidase are expressed by L. major promastigotes and alpha glucosidase is secreted by several trypanosomatid genera, but not by all those examined. Primers originally designed to amplify P. papatasi amylase DNA sequences, by polymerase chain reaction (PCR), also amplified DNA from all Old World Leishmania species, indicating that the gene is highly conserved between sand flies and these parasites. PMID- 11770111 TI - Recent advances in the taxonomy of the New World leishmanial parasites. PMID- 11770112 TI - Molecular epidemiology and population genetics in Leishmania. AB - Polymorphic DNA sequences have been amplified using different PCR-based techniques and used for species identification, strain discrimination and population genetic studies in Leishmania. A PCR fingerprinting method that uses single non-specific primers generates species-specific banding patterns with some intraspecies variation. This approach can be used to identify Leishmania species and also to discriminate strains of different Leishmania species. Cultivation of the parasites is, however, mandatory. PCR-restriction fragment length polymorphism of the internal transcribed spacer (ITS) in the ribosomal operon differentiates all Leishmania species, except members of the L. donovani and L. brasiliensis complexes. ITS-single-strand conformation polymorphism or ITS sequencing can detect strain specific-variation (except in L. infantum); culturing is not required. Species of Leishmania exhibit different degrees of genetic variation (L. tropica > L. aethiopica > L. major > L. donovani). Population analysis using co-dominant DNA markers developed by sequence-confirmed amplified region analysis revealed a primarily clonal structure in a L. donovani population from Sudan and suggested that occasional recombination events may occur in this population. PMID- 11770113 TI - Emerging Leishmania/HIV co-infection in Africa. AB - The HIV/AIDS pandemic is spreading at an alarmingly high rate in Africa. Leishmaniasis is also highly prevalent in the continent. Despite the emergence of Leishmania/HIV co-infection in Africa, the numbers reported are disproportionately low. Moreover, the number of cases of co-infection is expected to rise in Africa owing to the simultaneous spread of the two infectious diseases and their increasingly overlapping geographical distribution. PMID- 11770114 TI - Development and application of 'simple' diagnostic tools for visceral leishmaniasis. AB - The diagnosis of visceral leishmaniasis is difficult. Due to the limitations of direct methods to detect parasites, indirect immunological methods are widely employed. The simple affordable and sensitive/specific direct agglutination test (DAT) is perhaps the most important diagnostic tool under field conditions. A significant improvement of this test is the use of a freeze-dried antigen, which is heat-stable and has a long shelf-live even under harsh conditions. The performance of this antigen in DAT has been evaluated using samples collected in East Africa. The results of these studies are presented. The detection of Leishmania infection in HIV-co-infected patients is difficult. The combination of DAT-PCR may be useful for the detection of parasite infection in these patients. Finally, we present data to show that the DAT based on the freeze-dried antigen can also be used for the detection of anti-Leishmania antibodies in dogs. PMID- 11770115 TI - Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice. AB - In the present study the early recruitment of leukocytes into the infected skin and into the draining lymph node (LN) was investigated after subcutaneous infection of mice with Leishmania major promastigotes. Flow cytometric analysis of cells recovered from the infected skin revealed that GR-1+ granulocytes were present as early as 10 h after infection, thus representing the first leukocyte population to be recruited to the site of infection. The migration of granulocytes was shown to be associated with a rapid mRNA expression of the neutrophil-attracting chemokine KC in the infected skin. Moreover, L. major promastigotes were found to produce factor(s) that are chemotactic for human neutrophils in vitro. Experiments with human neutrophils revealed that these cells are able to phagocytose the parasites. Natural killer (NK) cells appeared at the site of infection 24 h after infection. The migration of NK cells in resistant mice was found to correlate with the expression of the NK cell activating chemokine IP-10. Treatment of susceptible BALB/c mice with recombinant mouse IP-10 resulted in a significantly increased NK cell cytotoxic activity in the draining LN. These data suggest that both the early chemokine gene expression and the production of chemotactic factors by the parasites themselves regulate the site-directed migration and activation of cells of the innate immune response, and suggest a role of chemotactic factors in the early defense against the parasites. PMID- 11770116 TI - Worldwide increasing risk factors for leishmaniasis. PMID- 11770117 TI - Current issues in the treatment of visceral leishmaniasis. PMID- 11770118 TI - Development status of miltefosine as first oral drug in visceral and cutaneous leishmaniasis. AB - An oral treatment for visceral and cutaneous leishmaniasis has been searched for over the last decades. An oral drug would facilitate treatment and lower costs. Oral miltefosine (Zentaris/ASTA Medica AG, Germany), an alkylphosphocholine, is under clinical development for treatment of leishmaniasis. Phase I, II and III clinical trials have been performed in visceral leishmaniasis in India; the overall response rate with 100 mg/day over 4 weeks is 96%. A first clinical trial in New World cutaneous leishmaniasis has shown a final cure rate of 94% at a dose of 150 mg/day over 3 or 4 weeks. Side effects are mainly gastrointestinal (vomiting, diarrhoea). Furthermore, transient elevation of transaminases or urea/creatinine has been observed. The clinical results suggest that miltefosine is the first oral therapy that is effective and safe in visceral and cutaneous leishmaniasis. PMID- 11770119 TI - Treatment of visceral leishmaniasis. AB - Growing antimony resistance in patients with visceral leishmaniasis (VL) over last two decades, especially in Indian subcontinent, renders this cheap and easily available drug useless for a vast majority of patients. Use of the second line drug pentamidine isethionate, a toxic drug with declining efficacy, has largely been abandoned. Thus, in these areas amphotericin B remains the only drug; although it cures > 97% patients, infusion-related adverse events are common and occasionally serious toxicity, such as myocarditis, or death can occur. In recent years India has been the center for clinical development of new anti-leishmanial drugs like lipid formulations of amphotericin B, new drugs like parenterally administered aminosidine and oral miltefosine. The alkyl phospholipid compound miltefosine is the first effective oral compound for VL and is likely to be marketed soon. In addition to the monotherapy, efforts in development of combination chemotherapy are needed if the menace of drug resistance is to be contained. PMID- 11770120 TI - The Leishmania genome project: new insights into gene organization and function. AB - The sequencing of Leishmania major Friedlin chromosome 1 (Chr1), Chr3, and Chr4 has been completed. and several other chromosomes are well underway. The complete genome sequence should be available by 2003. Over 1,000 full-length new genes have been identified, with the majority (approximately 75%) having unknown function. Many of these may be Leishmania (or kinetoplastid) specific. Most interestingly, the genes are organized into large (> 100-500 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a "divergent" manner, i.e., the mRNAs for the two sets of genes are both transcribed towards the telomeres. Nuclear run-on analysis suggests that transcription is initiated in both directions within the "divergent" region. Chr3 and Chr4 contain two "convergent" clusters, with a single "divergent" gene at one telomere of Chr3. Sequence analysis of several genes from the LD1 region of Chr35 indicates a high degree of sequence conservation between L. major and L. donovani/L. infantum within protein-coding open reading frames (ORFs), with a lower degree of conservation within the non coding regions. Immunization of mice with recombinant antigen from two of these genes, BTI (formerly ORFG) and ORFF, results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania. PMID- 11770122 TI - Ultrastructure of apoptotic oligodendrocytes in the spinal cord of adult rat with long-standing axotomised sciatic nerve. AB - The apoptosis in the oligodendrocytes was evaluated in adult rat which were axotomised and sacrificed three months aftersurgery. The apoptotic cell had electron dense organelles with condensed cytoplasm, the nucleus showed chromatin condensation with formation of band-like structure of clumped chromatin, and subsequently the cell underwent progressive shrinkage. The advanced stage of apoptosis showed electron lucency in the chromatin band, followed by disintegration of the nucleus, while the cytoplasm was replaced with high electron dense granular substance forming round electron dense apoptotic cells. The autophagy was also noticed in the cytoplasm of these cells, consisting of membrane bounded cytoplasmic organelles. Because the autophagy was seen in the apoptotic cell, this indicates that the autophagy is not limited to autophagic type programmed cell death. PMID- 11770121 TI - Chemotherapy of cutaneous leishmaniasis: a review. AB - A wide variety of treatment modalities have been employed for cutaneous leishmaniasis (CL); however, none has been demonstrated to be good enough to be used as the first-line drug to treat patients in all the CL epidemiological scenarios. Although pentavalent antimonials remain a drug widely used in the treatment of all forms of leishmaniasis, they are far from being satisfactory. A great variety of topical treatments have been used to treat CL. However, the majority of these modalities have been tested in non-controlled studies, with only few subjects and the interpretation of results is usually difficult due to the lack of a standard and well-accepted cure definition. Several oral drugs, such as ketoconazole and itraconazole, have also been tested for CL, but results obtained were not completely satisfactory. As of today, miltefosine, originally developed as an oral antineoplastic agent, seems, from the preliminary results obtained in different phase II clinical studies, to be the most promising oral drug developed during the last decade. PMID- 11770123 TI - Ultrastructural characteristics of necrotic and apoptotic mode of neuronal cell death in a model of anoxia in vitro. AB - Increasing evidence suggests that two distinct modes of cell death, known as apoptosis and necrosis, are involved in many different pathological states. The morphological pattern of postanoxic changes has been widely studied in various experimental models, however the exact mechanism of neuronal cell death induced by ischaemic/anoxic insult is still not fully understood. The aim of this study was to determine the detailed ultrastructural criteria of postanoxic neuronal changes in in vitro model of anoxia. The electron-microscopic examination of organotypic cultures of rat hippocampus, exposed to 10- and 20-minute anoxic insult, revealed the morphological features typical for both necrotic and apoptotic neuronal cell death. Numerous neurones revealed a typical picture of passive necrotic lysis, such as advanced swelling of intracellular organelles associated with cell membrane disruption, whereas others clearly reflected an active apoptotic form of cell injury, consisting of condensation of nuclear chromatin with early preservation of cell membranes. However, there was also a subset of damaged cells sharing several features typical for both necrosis and apoptosis. These results add additional evidence to the previous studies suggesting not only that neurones injured by anoxic insult can die in a pure necrotic or apoptotic way but also that a continuum might exist between apoptosis and necrosis in certain pathological conditions. PMID- 11770124 TI - CDP-choline, but not cytidine, protects hippocampal CA1 neurones in the gerbil following transient forebrain ischaemia. AB - The effects of CDP-choline (citicoline), cytidine monophosphate or cytidine on the number of CA1 hippocampal neurones surviving five-minute forebrain ischaemia have been evaluated in gerbils. The substances tested were given in daily doses equivalent on a molar basis to 500 mg/kg CDP-choline, starting immediately after ischaemia. On day five the brains were perfused, postfixed, cut into 10 microm slices and stained with cresyl violet, and the number of neurones in the CA1 sectors was counted manually under a light microscope at magnification x 400. The results indicate a significant degree of protection provided by citicoline, but no protection by cytidine monophosphate or cytidine. The choline moiety of CDP choline appears to be essential for the neuroprotective properties of the drug. PMID- 11770125 TI - Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. AB - Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants- coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme- caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment. PMID- 11770126 TI - Blood-brain barrier disturbances and morphological changes in rat brain after photochemically induced focal ischaemia. AB - The disturbances in cerebral circulation lead to focal brain ischaemia and brain infarcts. The pathogenesis of brain ischaemia has been a subject of numerous experimental studies employing different models and focusing on the anatomy of collateral circulation. The aim of this study was the evaluation of our own model of focatcerebral damage caused by a photodynamic reaction, and determination of its utility as a model of brain necrosis and blood-brain barrier damage in the rat. Wistar rats were used for the experiments. The animals were anaesthetised with 3% chloral hydrate (325 mg/kg) and injected intravenously with 40 mg/kg of 3% solution of rose bengal. After removal of the periostium the brain was irradiated through the skull for 30 min with a 250 W halogen, air-cooled light source. The material for morphologic studies was sampled 24 h, 4 days and 7 days after irradiation. The brains were fixed by perfusion, embedded in paraffin, and stained with haematoxilin-eosin (HE), acid vanadium fuchsin, cresyl violet, and GFAP. The results document the usefulness of this method for studying focal brain ischaemia in rats. The observed morphological changes and disturbances in blood brain barrier provided information about the dynamics of the formation of gliosis, the formation of necrotic foci, and the quality and extent of brain damage in the surrounding tissue. PMID- 11770127 TI - Excitotoxicity-induced expression of amyloid precursor protein (beta-APP) in the hippocampus and cortex of rat brain. an electron-microscopy and biochemical study. AB - After stereotaxic microinjection of N-methyl-D-aspartate (NMDA) or alpha-amino-3 hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) to CA1 of rat hippocampus, the animals were sacrificed: 0 h, 2 h, 12 h, 24 h and 3 days after the insult. Other groups of animals before microinjection of the excitotoxins received intraperitoneal injection of dizocilpine (MK-801). Expression of beta-APP was assessed by immunohistochemical and immunobiochemical methods, and the results were correlated with changes in tissue ultrastructure observed in the electron microscopy. The results of the immunochemical analyses study demonstrated that application of NMDA and AMPA resulted in the increase of the expression of beta APP in the CA1 of hippocampus and to a less extent in the cortex. Pretreatment with MK-801 strongly suppressed this effect. Beta-amyloid release was not detected. Morphological and cytochemical study revealed that NMDA injection induced massive damage of hippocampal and cortical neurones, associated with mitochondrial calcium sequestration and unusual accumulation of neurofilaments. Ultrastructural changes after AMPA application were limited to the brain cortex. These data indicate that although excitotoxic insult induces hyperexpression of beta3-APP, there is no relation between this effect and neurodegeneration, and excitotoxicity does not induce amyloidogenic processing of beta-APP. PMID- 11770128 TI - Epidemiological studies on Creutzfeldt-Jakob disease in Poland. AB - The epidemiological, clinical and neuropathological study of Creutzfeldt-Jakob disease (CJD) in Poland was established in 1996. It was preceded by wide, repeated informative action among neurologists and psychiatrists in the whole country. The investigations were partially sponsored by the European Commission (E.C.) as part of the programme Biomed 1. The results obtained by us during the first three years of the study are presented in this paper. In 1996-1998 over 60 probable or possible cases of CJD (or information about them) were referred to our Institute. Neuropathologically typical changes for spongiform encephalopathy were found in 28 cases (among them four cases in laboratories of Medical Schools in Szczecin and Poznan). Neuropathological evaluation was based on paraffin slices stained by H-E, PAS, Bielschowsky, Kanzler-Arendt and Kluver-Barrera methods. In certain cases antibody 3F4 was used. In three patients only clinically probable CJD were diagnosed, since neuropathology was not done. In twenty-five persons, a detailed inquiry form was filled in after the model indicated by the E.C. As the result of processing the whole material, we diagnosed in twenty-four patients a sporadic form of CJD. The remaining case belonged to a family with Gerstmann-Straussler-Scheinker syndrome. In sporadic CJD cases examined and observed by us no exogenic risk factors for the disease could be detected. PMID- 11770129 TI - Neurones and microglia in central nervous system immune response to degenerative processes. Part 1: Alzheimer's disease and Lewy body variant of Alzheimer's disease. Quantitative study. AB - The quantitative correlation between neurone loss and brain immune response, assessed by intensity of microglia inflammatory reaction in cortical association area and limbic cortex, was investigated and compared in previously immunohistochemistry (IHC) and ultrastructural confirmed 11 cases of Alzheimer's disease (AD), 7 cases mixed form of Dementia with AD findings and Lewy bodies (AD/DLB) reported, in accordance with Consortium on Dementia, as Lewy body variant of AD (LBV) and 6 non-demented autopsy control cases from 63 to 86 years old. In the present work we investigated association and limbic cortical areas linked with memory mechanisms; there are regions characterised by early distribution of IHC confirmed AD and DLB/AD (LBV) markers, as well as a substantial physiological stability of neurone pool regardless of age. The results indicated that AD and LBV differ in their neurone loss intensity and inflammatory reaction, with much higher intensity in AD. In Alzheimer's disease, neurone loss in association temporal cortex made up 51% of control values with simultaneous 8-fold increase in the density of MHC II-positive activated microglia, whereas in LBV, both the loss of neurone density and the increase in activated microglia density, was not so high (up to 41% and 4-5-fold, respectively). Changes in the limbic cortex were less pronounced. A strong correlation in the clinical material between neurone loss and microglia activation in both processes, especially in AD (r = 0.73), speaks in favour of the hypothesis on the neuronal immune surveillance and arousal of immune brain response in conditions of declining control, due to significant neurone loss in the neurodegenerative process. The inflammatory reaction of MHC II-immunoreactive microglia, concomitant with neurodegenerative process, seems to be a consequence of increased immune response due to loss of neurones and weakening of their control upon immunosurveillance in central nervous system. PMID- 11770130 TI - Ultrastructural changes in neuronal and glial cells in subacute sclerosing panencephalitis: correlation with disease duration. AB - This paper presents ultrastructural changes in neuronal and glial cells with special reference to intranuclear inclusion bodies in subacute sclerosing panencephalitis (SSPE) with different duration (from several weeks to seven years). Brain autopsy at ultrastructural level revealed the nucleocapsids of paramyxovirus in neuronal and oligodendroglial nuclei in 4 of 6 SSPE cases under study. Nucleocapsids of measles virus were present in two cases of disease lasting several weeks and in two cases with disease duration of two years, while abundant nuclear bodies and granulofilamentous inclusions in astrocytic nuclei were found in all cases. Occasionally, both granulofilamentous inclusions and complex nuclear bodies occurred in the same astrocytic nucleus. Only in the case lasting seven years they were not observed. It is likely that there is a structural and morphological relationship between these two types of inclusions present in astrocytic nuclei. Nuclear bodies and granulofilamentous inclusions were common and independent of the presence or absence of virus nucleocapsids. In the case of SSPE with a seven-year duration but without viral nucleocapsids in neuronal and oligodendroglial nuclei, neuronal tangles were observed. PMID- 11770131 TI - The fractal analysis of subdural haematoma. AB - The fractal analysis of vessel structure in the capsule of subdural haematoma has been performed. Examined material comprised 100 normal cases and 30 with long lasting subdural haematoma. Pickworth's method and computer image processing under lmtron, Scion for Windows 98 were applied. The parallel vessels with fork like branching were found in the subdural haematoma capsule. The essential result of the fractal analysis was that there was no difference in one-sided dimensions of subdural haematomas in contrast to differentiated one-sided dimensions of normal vessels. This finding may explain the continuous growth of subdural haematoma. The applied method allows observation of the microangioarchitecture in the capsule of subdural haematoma. PMID- 11770132 TI - Disseminating histologically benign multiple papilloma of the choroid plexus: case report. AB - A rare case of extensively disseminating multiple benign choroid plexus papilloma is shown. The patient first reported with high-grade hydrocephalus and two tumours in the 3rd and 4th ventricle was treated by atrioventricular shunt insertion, subtotal resection of the 4th ventricle tumour, and adjuvant 60Co irradiation of the posterior fossa. The dissemination that followed was revealed by computerised tomography and magnetic resonance imaging, and involved both the supra- and infratentorial ventricular systems, spinal canal, and brain parenchyma. Three years after the resection of the 4th ventricle tumour, the patient underwent excision of a temporal lobe lesion for relief of neurological symptoms, but showed no improvement and died 5 years after the primary diagnosis of CNS tumour. An autopsy was not performed. Analysis of the primarily resected mass showed distinct papillary pattern with no anaplasia, mitoses, multinucleation orgiant cell formation, and cytokeratin positivity at the absence of vimentin and glial fibrillary acidic protein. Analysis ofthe temporal lobe tumour again showed definite papillary formation with no signs of malignisation and virtually no mitotic figures, and the presence of cytokeratin, but not vimentin or glial fibrillary acidic protein. On both occasions, the diagnosis was choroid plexus papilloma (WHO grade I). PMID- 11770133 TI - Otology's past, present, and future. PMID- 11770134 TI - The specialty of rhinology, part 1: a historical glimpse. PMID- 11770135 TI - The specialty of rhinology, part 2: into the new millennium. PMID- 11770136 TI - Otolaryngology in the millennium: paediatric otolaryngology--past, present, and future. PMID- 11770137 TI - Medical publishing: the future. PMID- 11770138 TI - Toward a standard for electronystagmography. AB - Although the adoption of a standard is desirable, no person or laboratory will be entirely happy with whatever standard because ENG testing has become so individualized. Hopefully, a standard that will enhance patient care can be implemented without much cost. PMID- 11770139 TI - Effects of dimenhydrinate on computerized dynamic posturography. AB - OBJECTIVE: Previous studies have demonstrated that sedatives and antiemetics commonly used by patients suppress the vestibulo-ocular reflexes during electronystagmography, making it more difficult to quantify function in such patients. The effects of these medications on computerized dynamic posturography (CDP) have not been studied, and the influences, if any, on the vestibulospinal reflexes are not known. We aimed to study the influence, if any, of dimenhydrinate on CDP performance. DESIGN: A double-blinded study using a randomized protocol to compare the effects of dimenhydrinate and placebo on CDP performance in normal subjects. SETTING: A tertiary/quaternary care facility using a standardized CDP assessment protocol. METHODS: After a CDP training session (one assessment) to rule out any learning effect, 10 subjects underwent CDP assessment on 2 separate days after ingestion of either a standard single dose of dimenhydrinate or placebo. MAIN OUTCOME MEASURES: Pre- and post medication CDP performance was measured using Sensory Organization Test (SOT) composite scores and also scores on CDP conditions particularly sensitive to measurement of vestibular impairment (SOT conditions 5 and 6). RESULTS: Analysis of data showed no significant effect on CDP performance of normal subjects after dimenhydrinate administration, although there may be a trend toward a slight effect on performance. CONCLUSIONS: There seems to be no significant effect of dimenhydrinate on CDP performance in normal subjects, although there may be a trend. Further studies using a dose causing more significant symptoms or using a higher number of subjects may clarify this. PMID- 11770140 TI - Efficacy of surgical salvage for advanced neck metastases after radiotherapy failure. AB - OBJECTIVE: To analyze the efficacy of surgical salvage in patients with metastatic squamous cell carcinoma to the neck of stage N2 or N3 initially treated with radiotherapy. DESIGN: Retrospective review. SETTING: Tertiary care institution. METHODS: Four hundred and twenty-five patients received neck dissection at Sunnybrook Health Sciences Centre between 1990 and 1996. Sixty-one patients had neck dissection for salvage after radical radiotherapy for advanced neck disease of stage N2 or N3. These patients were selected from the Sunnybrook Head and Neck Database and reviewed. OUTCOME MEASURES: Survival and recurrence. RESULTS: Sixty-one patients underwent neck dissection for salvage after radiotherapy. Five-year overall survival was 30%. The majority (72%) failed locoregionally after surgical salvage. CONCLUSIONS: Surgical salvage after radiotherapy for advanced neck disease has a 30% 5-year survival rate. Surgical salvage after radiotherapy for advanced neck disease is effective in a minority of patients. PMID- 11770141 TI - Acoustic neuroma: postoperative quality of life. AB - OBJECTIVE: Evaluating patients who have had surgical management of acoustic neuroma has relied heavily on the surgeon's viewpoint for determining success. However, the perspective of the surgeon may be different from that of the patient. Thus, a recent increased interest in terms of quality of life has been documented by the literature on this specific topic essentially through the use of a questionnaire. The objective of this paper was to review this topic in our series of patients operated on for acoustic neuroma to ascertain the personal and social impact that surgery has had on their lifestyle. DESIGN: This retrospective study was devoted to increasing statistics to provide more detailed and valid information during the counselling phase. METHODS: This study was carried out on 82 patients who underwent surgery for acoustic neuroma between 1988 and 1997. Each patient was recalled and assessed for his/her postoperative quality of life. Detailed information was requested on the initial postoperative facial, vestibular, and hearing functions; their evolution; and their social consequence. Finally, at the end of the interview, each patient was invited to give a final comment on his/her opinion regarding the outcomes of surgery and preoperative information. RESULTS: Facial function showed a grade I-III in 85.4% of cases, with postoperative neurovegetative dysfunction (taste and lacrimation) in 43%. Audiologic abnormalities (worsening hearing and tinnitus) were complained of in 90% and 57% of the cases, respectively. Twenty-three percent of the patients had various degrees of gait instability; 6% reported postoperative headache at 1-year follow-up. Social consequence (reduced work ability, vocational change, new education, state pension, etc.) was not influenced by surgery in 80%. CONCLUSIONS: Our experience is in general agreement with previously reported statistics. It is interesting to note that our patients exhibited more disturbances linked to the sensory component of facial nerve. In contrast, dysequilibrium had a less negative influence. These outcomes suggest the importance of thorough preoperative counselling in candidates for surgery for acoustic neuroma in order to motivate them and, at the same time, to reduce their psychological discomfort. PMID- 11770142 TI - Ultrasonic tonsillectomy. AB - High-frequency ultrasound is an effective mechanism for cutting and coagulating tissue. It is widely used in laparoscopic surgery and may have advantages in tonsillectomy. Twenty-five consecutive cases of tonsillectomy were performed using an ultrasonic scalpel; these were compared with a similar previous consecutive group performed by conventional cold dissection and monopolar electrocautery. There was no undue primary bleeding in either group and no immediate or late postoperative bleeding. Since adenoidectomy was often performed and the total blood loss in each group was so small, no statistical difference could be determined between the groups. No complications were noted in either group. The ultrasonic scalpel has the potential to produce a bloodless tonsillectomy and less collateral tissue damage and is easy to use. There may be less postoperative pain, although this could not be shown statistically in this retrospective study. Ultrasonic tonsillectomy appears to be a safe, and possibly a superior, method of performing this common operation. PMID- 11770143 TI - Regeneration of the mammalian vestibular sensory epithelium following gentamicin induced damage. AB - OBJECTIVES: The aims of this study are (1) to investigate if significant long term recovery of mature hair bundle (MHB) numbers takes place following gentamicin-induced damage to the mammalian vestibular sensory epithelium and (2) to assess if the different MHB types in the vestibular sensory epithelium have a different susceptibility to ototoxic damage. METHODS: Gentamicin (8 mg in 0.1-mL sterile water) was injected transtympanically into one ear of guinea pigs, the contralateral ear acting as a control. The animals were killed at 4 days, 4 weeks, and 3 and 10 months post-treatment and the utricles (n = 38) were extracted from both ears. Mature hair bundle and immature-looking hair bundle (IHB) densities on the surface of the utricle were determined using scanning electron microscopy. RESULTS: The MHB density showed a significant decline between 4 days and 4 weeks post-treatment. There was greater loss of type I MHBs (tallest stereocilia comparable in height to the kinocilium) than type II MHBs (kinocilium taller than the tallest stereocilia). A significant increase in IHB density was seen at 4 weeks post-treatment, after which it declined rapidly. A significant but incomplete recovery in MHB density (to 66% of control value) was seen in the striolar region at 10 months post-treatment, and these were composed mainly of type II MHBs. CONCLUSIONS: It would appear that the mature mammalian vestibular sensory epithelium does have the capacity for long-term recovery of MHB numbers following gentamicin-induced damage, but this is limited and does not result in complete restoration of the epithelium. Type I MHBs are more susceptible to ototoxic damage than type II MHBs. Sommaire PMID- 11770144 TI - Systemic steroids for the management of obstructive subglottic hemangioma. AB - Subglottic hemangioma is a recognized cause of paediatric upper airway obstruction. We present 14 patients with subglottic hemangioma treated between 1984 and 1997,4 of whom had associated extralaryngeal hemangiomatous lesions (28%). The degree of upper airway obstruction ranged between 20% and 90%. Patients with subglottic hemangioma who had obstruction of the laryngeal lumen more than 25% and those with obstructive symptoms were treated with systemic steroids. The patients were followed clinically, radiographically, and with repetitive bronchoscopies. Nine of 10 patients (90%) have responded clinically to systemic steroids. There were no major complications from the systemic steroid treatment. One patient developed a cushingoid face that was reversed after the cessation of steroid therapy. The purpose of this study is to show that systemic steroids, with or without short-term intubation after diagnostic bronchoscopy, can be used as a safe and effective alternative in the management of obstructive paediatric subglottic hemangiomas. PMID- 11770145 TI - Effect of the external nasal dilator on nasal minimal cross-sectional area in orientals as assessed by acoustic rhinometry. AB - OBJECTIVE: This study aimed to evaluate the effect of the external nasal dilator on the dimension of the nasal valve in Orientals. DESIGN: A cohort study of normal subjects. SETTING: Academic institution. METHODS: The nasal fossae of normal subjects were assessed by acoustic rhinometry before and after application of the external nasal dilator. MAIN OUTCOME MEASURES: The minimal cross-sectional area of the nasal fossae and the total cross-sectional area of the nose. RESULTS: Nasal fossae of 25 normal subjects were evaluated. There was a significant increase of 0.10 cm2 (SD = 0.16) or a 17% increase in the minimal cross-sectional area of the 50 nasal cavities after application of the external nasal dilator (Wilcoxon's matched-pairs signed rank test, p = .0001). A significant increase in the total minimal cross-sectional area for the whole nose after application was also present (0.19 cm2, SD = .27, or 16%; Wilcoxon's matched-pairs signed rank test, p = .0032). CONCLUSIONS: The external nasal dilator results in an increase in the minimal cross-sectional area of the nasal airway in Orientals. PMID- 11770146 TI - DNA analysis of laryngeal carcinoma cells by flow cytometry: the histoclinical factors and their significance. AB - In patients suffering from several types of malignant tumours, changes in deoxyribonucleic acid (DNA) content are usually associated with poorer survival prognosis. In the present study, DNA content and clinical and histopathologic features were analyzed in patients suffering from laryngeal carcinoma, with a view to establishing the crucial prognostic factors. In the 5-year follow-up study, flow cytometry was used to analyze DNA content in the paraffin-embedded samples of laryngeal carcinoma tissue obtained from 90 patients who had undergone surgical treatment in the Department of Otolaryngology, Collegium Medicum, Jagiellonian University, Cracow, Poland, in 1987 and 1988. The group consisted of 59 and 31 patients with T3 and T4 tumours, respectively. In each case, neck dissection was carried out either on one or both sides. Metastases in regional lymph nodes were found in 26 patients. The disease-free 5-year survival rate was 55.6%. Among the investigated cases, there were 14 aneuploid and 76 diploid tumours. The treatment yielded the worst results, when the S-phase fraction (SPF) and proliferative index (PI) were equal to or higher than 15.8% and 16.0%, respectively. The values of SPF and PI index did not correlate, however, with the frequency of regional metastases. Univariate analysis revealed that tumour size (T stage), presence of lymph node metastases, age of patients (< or = 60, > 60), tumour differentiation, tumour front grading (<15 points, > or = 15), mode of infiltration, SPF, and PI were positively correlated with the actual survival rate. Presence of lymph node metastases (p = .0001) and the PI (p = .0067) were found to be the only independent prognostic factors when the Cox multivariate analysis was applied. The assessment of the PI by flow cytometry may effectively facilitate the selection of patients recommended for a more aggressive treatment. PMID- 11770147 TI - Laser facial resurfacing: patient survey of recovery and results. AB - OBJECTIVE: To determine patient satisfaction with the postoperative recovery period and surgical outcome after facial laser resurfacing. DESIGN: Survey. PATIENTS: Patients who underwent facial laser resurfacing by two of the authors (PAA or DAFE) between 1995 and 1996. Questionnaires were completed by 47 of 100 patients. INTERVENTIONS: Facial laser resurfacing with the Sharplan CO2 laser and SilkTouch Scanner. MAIN OUTCOME MEASURES: Questionnaire. Statistical analysis was generated from a 5-point analogue scale. RESULTS: The overall side effects were moderate in severity, were well tolerated, and met the expectations of our patients. Redness was the most frequent side effect with an average duration of 3 months. Most patients returned to occupational and social activities at 2.5 weeks. Moderate lifestyle disruption was more frequent after full-face laser resurfacing than partial-face laser resurfacing. Excellent improvement was achieved for removal of fine wrinkles, improvement of skin quality, and sun damaged skin. Good improvement was obtained for acne scarring and deep rhytids. Overall goals were attained in 89% of patients. CONCLUSIONS: Laser resurfacing produced excellent results for fine rhytids, skin quality, and sun-damaged skin. Return to social and occupational activities may occur early in recovery with the use of camouflage make-up. Patient education and close follow-up are necessary in the postoperative period. PMID- 11770148 TI - Otolaryngologic diseases and medical treatment during the Byzantine period. PMID- 11770149 TI - A new technique of sural nerve harvest. PMID- 11770150 TI - Adenocarcinoma of the paranasal sinuses: two case reports in a child and an adolescent. PMID- 11770151 TI - Malignant epithelioid peripheral nerve sheath tumour of the pterygopalatine fossa. PMID- 11770152 TI - Unilateral parotid swelling as initial manifestation of Wegener's granulomatosis. PMID- 11770153 TI - Case study of groundwater pollution in a critical area of the Southern-Friuli exposed to agricultural and landfill pressures. AB - Groundwater of the Southern-Friuli displays high levels of agricultural pollutants, such as nitrates and triazinic herbicides not only in the surficial layers, but also in the deeper ones, below 150 m. Some wells of the district of Gonars was monitored. The examined waters, used for irrigation but also for drinkable use, are exposed to environmental risk due to both agricultural practices and presence of many waste disposal sites. Heavy metals, nitrates and triazinic herbicides were measured in samples taken at four wells in three periods having different rain conditions. We found that groundwater quality is affected mainly by agricultural practices: nitrates and triazines are present at levels very near as well as superior to the maximum concentration allowable by Italian law. These agricultural contaminants have similar levels at all sampled sites: no difference was detected between dry periods and rain ones. Heavy metal contents are negligible in all cases; this fact suggests that ion-exchange, sorbing and complexing properties of the soils hinder the way of the metal leachates towards underlying groundwater. Zinc constitutes an exception; it is found at levels near or superior to the maximum allowable concentration (CMA), and the highest contents are observed in rain periods; different sites display different zinc levels, suggesting that this metal could have various point sources. Nitrates fertilisers were found in all sites at similar levels, very near to CMA (50 mg/L). Triazines are specific herbicides for corn growing, highly diffused here: their use in recent years is forbidden by Italian law, but the presence in groundwater of parent triazines and metabolites is a persistent problem of this area. The Italian law indicates a CMA of 0.10 microgram/L for the sum of atrazine and desethylatrazine, but we found that desethylatrazine by itself exceeds largely CMA in all sites. PMID- 11770154 TI - The complexation of mercury (II) and organomercurial compounds by 8 hydroxyquinoline-bovine serum albumin conjugates. AB - The complexing properties of conjugates between 8-hydroxyquinoline and bovine serum albumin (Ox-BSA) towards inorganic and organic mercury were studied. Two Ox BSA conjugates (different substitution ratio) were prepared and their complexing properties were studied. Through the use of titration curves with mercury (II), methylmercury and ethylmercury an evaluation of the complex stoichiometry and stability was obtained, showing that Ox-BSA has good affinity for all investigated mercuric compounds and that the stability increases in the order: Hg (II) < CH3Hg+ < C2H5Hg+, whatever conjugate is considered. Complexes show a stoichiometry of 1:1 between mercury and 8-hydroxyquinoline residues, except with the high substituted conjugate and Hg2+ ion. The skill of the high substituted conjugate to bind inorganic and organic mercury in the presence of NaCl was also studied. Organic mercuric complexes do not show significant modification due to NaCl. Nevertheless, considering inorganic mercury, the number of retained metal ions per protein molecule increases if the NaCl concentration becomes higher than 0.1 M, probably because at high NaCl concentrations 1:1 complexes between mercury and 8-hydroxyquinoline are preferred to 1:2 complexes. PMID- 11770155 TI - On-line purge-and-trap-gas chromatography with flame ionization detection as an alternative analytical method for dimethyl sulphide trace release from marine algae. AB - The release of dimethyl sulphide (DMS) by the seaweed Ulva spp at trace level was studied in aqueous solutions at different salinities, temperature and light intensities. For this purpose, the purge-and-trap technique combined with gas chromatography-flame ionization detection was used. The analytical method was evaluated in terms of linearity range, limit of detection, precision and accuracy by considering 10@1000 (w/v) and 30@1000 (w/v) synthetic seawater as aqueous matrices. Calculation of the recovery function evidenced a matrix influence. The method of standard addition was then used for an accurate determination of DMS in synthetic seawater reproducing the matrix effect. DMS fluxes were analysed in batch cultures of Ulva spp reproducing the conditions which usually occur in the Sacca di Goro lagoon (Northern Adriatic Sea, Italy). PMID- 11770156 TI - Anthropogenically derived mercury in sediments of Pialassa Baiona, Ravenna, Italy. AB - Pialassa Baiona, a coastal wetland near the city of Ravenna, has been impacted for two decades (1958-1978) by industrial discharges containing mercury and floating agglomerates of residues of polymerization processes. Although the industrial use of mercury completely ceased in the early 90's, surface sediments are still highly contaminated, mercury concentrations decreasing from the southern sub-basin, close to the discharge point, to the farthest northern border. Concentrations of total mercury, synthetic polymers (determined by pyrolysis-GC/MS), total organic carbon, C/N ratio, total sulfur and 210Pb dating, were determined in sediment cores collected in the southern and northern sub basins. Mercury and polymers exhibited parallel profiles with a peak corresponding to the historic emission record in the southern core, while in northern cores peaks of maximum concentration display a delay reflecting the time required for the pollutants to migrate. A recently developed mercury sequential extraction procedure was applied to the most polluted layers to study inorganic mercury speciation. Results indicate differences between the southern and northern areas, suggesting a more efficient binding of mercury to sediments in the southern sub-basin. PMID- 11770157 TI - Organic content of particulate matter in the atmosphere of Ouargla City, Algeria. AB - The particle-bound organic compounds comprising n-alkanes, n-alkanoic monocarboxylic acids, polynuclear aromatic hydrocarbons (PAH) and nitrated polynuclear aromatic hydrocarbons (NPAH) were investigated in ambient air of the Ouargla city area (Algeria) during a short campaign performed in November 1999. The distribution profile of n-alkanes was consistent with the petrogenic origin of aerosols, suggesting that they were related to torching processes of crude oil refuses in the petroleum extraction field located not far from Ouargla. Instead, the presence of n-alkanoic acids of low molecular weight was indicative of microbial activity experienced by the site. PAH levels were low when compared to other polluted areas. The presence of 2-nitrofluoranthene and 2-nitropyrene, which can result from in-situ nitration of fluoranthene and pyrene, was concurrent with the substantial depletion of the most reactive among PAH, suggesting that photochemical processes influence the composition of the Saharian atmosphere. PMID- 11770158 TI - Treatment options for tannery wastewater. I: Alkalinization with or without post ozonation. AB - This is the first of two papers each dealing with a specific technological option for replacing the Fenton's reagent with simpler processes for treating industrial wastewater. In particular, the paper reports the results of an investigation aimed to check, at lab scale, the effectiveness of a chemical process (i.e., alkalinisation with or without post-ozonation) for treating tannery wastewater whose residual COD, measured after conventional biological treatment, result still higher than the Italian COD Maximum Allowable Concentration (MAC) value (i.e., 160 mgO2/L). The results have demonstrated that when the value of residual COD lies in the range 200 divided by 250 mgO2/L, a simple alkalinisation with NaOH, up to pH 12.5, allows to reach the MAC value with an alkali consumption equivalent to the acid consumption required by the Fenton treatment and with a chemical sludge production significantly lower, i.e. approximately 0.7 kg(dry)/m3 instead of approximately 1.5 kg(dry)/m3. Conversely, when the value of the residual COD lies in a higher range (i.e. 300 divided by 350 mgO2/L), in order to reach the COD MAC value, alkalinisation (from pH 8 to pH 12.5) must be followed by an ozonation post-treatment. From the chemical stand point, the paper clearly demonstrates that analyzing only simple "gross parameters" (i.e., TSS, TOC, COD, BOD5 and EC20) it is possible to get useful information about the chemical properties of the organic pollutants occurring in tannery wastewater. PMID- 11770159 TI - New possible chelating agents of clinical interest for iron(III): 2 hydroxynicotinic acid and 3-hydroxypicolinic acid. A thermodynamic study. AB - The formation of complexes between iron(III) and two ligands of possible relevance to chelation therapy, 2-hydroxynicotinic acid and 3-hydroxypicolinic acid, in aqueous 0.6 m (Na)Cl at 25 degrees C, has been investigated by means of potentiometric titrations and UV measurements. In both cases several mononuclear complexes and their deprotonation products are formed. PMID- 11770160 TI - Reliable pKw values from potentiometric titrations: the striking effect of the titration final added volume. AB - Errors affecting the estimation of the ionic product of water from the potentiometric titration of weak acids have been analysed. A Fortran programme has been developed in order to simulate experimental titration data sets. This programme allows one to isolate experimental error sources and analyse their effect upon the final fitted equilibrium constant. pKw dependence with titration final added volume and the pK value of the weak acid, predicted with the simulation programme are coincident with experimental data, suggesting that obtaining reliable pKw values entails using experimental data of titrations up to a sufficiently large hydroxyl concentration which depends on the value of pK. PMID- 11770161 TI - Salting coefficients of carboxylic acids in various saline media. AB - Reported partition coefficients and solubility data at 25 degrees C were used to determine the salting coefficients of acetic, benzoic, o-chlorobenzoic, m chlorobenzoic, p-chlorobenzoic, o-hydroxybenzoic, m-hydroxybenzoic and p hydroxybenzoic acids in various saline media. Coefficients were calculated on the molarity and molality scales. Except for acetic acid, which exhibited a negative coefficient in two of the 29 electrolytes used, all the acids were found to have positive values in the studied media. Consequently, the presence of a salt decreases the solubility of these acids. PMID- 11770162 TI - Binary and ternary complexes of cadmium(II) involving Ethylenediamine-N,N' diacetic acid and amino acids or peptides. AB - The present work examines the acid-base equilibria of Ethylenediamine-N,N' diacetic acid (EDDA) and the formation equilibria of binary and ternary complexes of cadmium (II) with EDDA and amino acids or peptides. Cd(II) is found to form a 1:1 complex with EDDA. The ternary complexes are formed in a stepwise mechanism, whereby the EDDA binds to Cd(II), followed by ligation of the amino acid or peptide. The amino acid, lysine, forms protonated and deprotonated ternary complexes. The stability constants of the ternary complexes have been quantified in relation to the corresponding binary complexes. The concentration distribution of the various complex species has been evaluated. PMID- 11770163 TI - A new preconcentration and separation method for flame atomic absorption spectrometric determinations of some trace metal ions on a Diaion HP-20 column. AB - A preconcentration/separation method for determination of Cr(III), Cd(II), Bi(III) and Co(II) has been proposed. The analytes were adsorbed on a column filled Diaion HP-20 resin as metal-8-hydroxiquinoline complexes and desorbed from the column by using 10 ml of 1M HNO3 in acetone. The influences of some analytical parameters such as pH, amounts of oxine, type of eluent etc on the recoveries of chromium, cadmium, bismuth and cobalt were discussed. Effects of the various alkaline salts on the recoveries of the investigated ions were also examined. The method was applied for the determination of Cr(III), Cd(II), Bi(III) and Co(II) contents of table salt samples, some chemical grade alkaline salts produced in Turkey and a stream sediment standard reference material sample (GBW 07309) with satisfactory results (recoveries > 95%, relative standard deviations < 9%). The limit of detection for analyte ions (3s, N = 20) was between 23-305 ng/g. PMID- 11770164 TI - A solid liquid extraction and preconcentration method for the atomic absorption spectrometric determination of trace cobalt in various alloys and biological samples. AB - Cobalt is quantitatively retained as cobalt-2-nitroso-4-sulfonic acid (nitros-S) tetradecyldimethylbenzylammonium (TDBA+) ion-pair complex on microcrystalline naphthalene in the pH range 6.2-9.0 from a large volume of its aqueous solution of various complex samples. After filtration, the solid mass consisting of cobalt complex and naphthalene is dissolved in 5 ml of dimethylformamide (DMF) and the metal is determined by flame atomic absorption spectrometry (FAAS). Cobalt complex can alternatively be quantitatively adsorbed on tetradecyldimethylbenzylammonium chloride-naphthalene adsorbent packed in a column and determined similarly. The calibration curve is linear over the concentration range 0.2-11.5 micrograms of cobalt in 5 ml of the final DMF solution. In this case, 0.2 microgram of cobalt may be concentrated in a column from 250 ml of aqueous sample where its concentration is as low as 0.8 ng/ml. Eight replicate determinations of 3.0 micrograms of cobalt in the final DMF solution give a mean absorbance of 0.045 with a relative standard deviation of 1.8%. The sensitivity for 1% absorption is 59 ng/ml. The interference of a large number of anions and cations on the determination of cobalt has been studied and the optimum conditions developed utilized for its trace determination in various alloys and biological samples. The method may also be used for the determination of cobalt in some environmental samples. PMID- 11770165 TI - Complexation equilibria and spectrophotometric determination of thorium(IV) with Lawsone. AB - The complex equilibria of Th4+ with Lawsone (2-hydroxy-1,4-naphthoquinone, LAS) were studied spectrophotometrically in 40% (v/v) ethanol water at 25 degrees C and an ionic strength of 0.1 M (NaClO4). The absorbance graphs were analysed to demonstrate and characterize the complex forming equilibria. A simple, rapid, selective and sensitive method for the spectrophotometric determination of trace amounts of thorium(IV) is developed. The complex formed at pH 2.1-3.6 (epsilon = 0.27 x 10(4) cm2 mol-1, at lambda = 440 nm) allows the determination of 5.8-32 micrograms/ml thorium. The effect of interferences was studied. PMID- 11770166 TI - Effect of the salt bridge choice on the response of an ion selective electrode cell. PMID- 11770168 TI - The withdrawal of Baycol (cerivastatin). PMID- 11770167 TI - Changes of plasma redox parameters by hemodialytic treatment in patients with chronic renal failure. PMID- 11770169 TI - The safety of medicinal products--current attitudes--better or just new? PMID- 11770170 TI - John of Gaddesdon--Royal physician, churchman and warrior. PMID- 11770171 TI - Thalidomide, drug safety and early drug regulation in the UK. PMID- 11770173 TI - New antiplatelet agents: ticlopidine and clopidogrel. Antiplatelet therapy but at what cost? PMID- 11770172 TI - Low molecular weight heparins--a safer option than unfractionated heparin? PMID- 11770174 TI - [Disorders of interferon-gamma activation pathways: new group of primary immune deficiency diseases]. AB - Protective immunity to intracellular bacteria such as mycobacteria and salmonella depends on intact cell-mediated immunity. Major effector mechanisms of cell mediated immunity involve activation of macrophages by T helper-1 cytokines, particularly interferon-gamma. Patients with genetic deficiency of T helper-1 cytokines (IFN-gamma, IL-12) or T helper-1 cytokine receptors (IFN-gamma receptor, IL-12 receptor) are susceptible to infections with poorly pathogenic mycobacteria, and salmonella, suggesting that T helper-1 cytokines are essential in host defense against these pathogens. This review reports on the genetic and clinical characteristics of primary deficiencies of interferon-gamma activation pathways. PMID- 11770175 TI - [Human recombinant anti-HER2 monoclonal antibody--a new targeted treatment in breast cancer]. AB - The HER2 protein is encoded by the HER2/neu gene and it is homologous to the epidermal growth factor receptor. Overexpression of HER2, usually in association with gene amplification, occurs in approximately 25-30% of breast cancers. There are currently several different methods available to evaluate HER2 status, e.g. immunohistochemical (IHC), and fluorescence in situ hybridization (FISH) assays. The HER2 protein is a viable therapeutic target. The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) has demonstrated activity in clinical trials in women with metastatic breast cancer overexpressing HER2. The mechanisms of the action of this antibody involve disruption of DNA repair and induction of antibody-dependent cellular cytotoxicity. Response rates to the antibody given as a single agents in the treatment of HER2 overexpressing metastatic breast cancer have ranged from 12 to 27%. Patients who received trastuzumab in combination with chemotherapy had a significantly longer time to progression, higher overall survival compared with patients who had received chemotherapy alone. In the treatment of women with HER2 overexpressing tumors an overall response rate of 57% for combination trastuzumab plus paclitaxel compared with 25% for paclitaxel alone was found. Trastuzumab has an important role in the treatment of HER2 overexpressing metastatic breast cancer. Its place in adjuvant treatment has not been proved up to now. The optimal use of trastuzumab in the treatment of HER2 positive advanced breast cancer is under active investigation. Due to the high rate of clinical activity and low incidence of severe toxicity trastuzumab is a very promising drug in the treatment of breast cancer. The author's purpose was to summarize the results of the trials using trastuzumab treatment, and discuss the methods used to determine the HER2 status. PMID- 11770176 TI - [Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin]. AB - According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin. PMID- 11770177 TI - [Macrocytic anemia and neurological signs due to vitamin B-12 deficiency in a breast-fed infant of a strict vegetarian mother]. AB - Vitamin B12 deficiency is a very rare disease of infants and young children in Europe. Authors report a case of a 9.5-month-old infant who was exclusively breast-fed by his vegan mother and developed serious vitamin B12 deficiency in form of neurological regression, repetitive vomiting, drowsiness, dysphagia, obstipation, and tremor. A few days after intramuscular vitamin substitution his abnormal signs improved dramatically, hematological restitution was reached in six weeks. Authors describe the hematological and neurological signs, the diagnostic and differential-diagnostic pitfalls, therapy, prognosis, and prevention of this condition. Beside reviewing the literature they emphasize the importance of early recognition and intervention and the need of an appropriate doctor-parent cooperation in this disease. PMID- 11770178 TI - [Professor Gyorgy Huszar is 90 years old]. PMID- 11770179 TI - [National Institute of Rheumatology and Physiotherapy--established 50 years ago]. PMID- 11770180 TI - [Remembering Dr. Gabor Ditroi, professor of ophthalmology]. PMID- 11770181 TI - The ascent of woman. PMID- 11770182 TI - Executive summary: Stages of Reproductive Aging Workshop (STRAW). AB - A select group of investigators attended a structured workshop, the Stages of Reproductive Aging Workshop (STRAW), at Park City, Utah, USA, in July 2001, which addressed the need in women for a staging system as well as the confusing nomenclature for the reproductive years. PMID- 11770183 TI - Menopausal obesity--myth or fact? AB - Obesity, particularly with central fat distribution, and mortality from all causes are directly related in middle-aged women. Many studies have shown that women in their mid-life tend to gain weight, with a shift to visceral fat distribution. The etiology of perimenopausal obesity is not fully known, and it remains unclear whether excessive weight gain and changes in fat distribution at menopausal age result from climacteric changes or are related to the process of aging of the individual and/or to changing life-style factors. Obesity may have a genetic background. It is well established that an excessive amount of energy intake and too small an energy expenditure is crucial for the development of obesity. Diet composition also plays a role in the pathogenesis of obesity. Neuropeptides appear to be one of the factors that control food intake and nutrient balance. The aging process in women is associated with progressive declines in the levels of many hormones including estrogens, dehydroepiandrosterone (DHEA) and growth hormone-insulin-like growth factor I (GH IGF-I). These endocrine perturbations may result in altered body composition and weight gain. Obesity in postmenopausal women is accompanied by many metabolic disturbances leading to increased mortality. PMID- 11770184 TI - Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: a literature review. AB - This systematic review examines current literature relating to clinical studies of hormone replacement therapy (HRT) and tibolone, including selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and their usage in postmenopausal women with fibroids. After a MEDLINE search, 28 relevant articles were found in total, of which five concerned randomized controlled trials. The results from class I studies and class II studies are evaluated in the categories of those that involved tibolone only, those that involved HRT only, and those that involved SERMs such as tamoxifen and raloxifene. In conclusion, tibolone has no significant effect on myoma size in postmenopausal women. There is myoma growth in postmenopausal women taking HRT. However, this does not appear to cause clinical symptoms. PMID- 11770185 TI - Postmenopausal hormone replacement therapy use and risk of endometrial cancer in Japanese women. AB - The relationship between the risk of endometrial cancer and the use of noncontraceptive estrogens by Japanese postmenopausal women was investigated in a hospital-based case-control study of 1025 women with endometrial cancer and 1267 with other conditions. The overall odds ratio (OR) for estrogen use with or without progestins, compared with never use of any type of estrogens, was 0.917 (95% confidence interval (CI) 0.622-1.353), suggesting that hormone replacement therapy is not a causative agent for endometrial cancer in Japanese women, and that a recent increase in the incidence of endometrial cancer in Japanese women may be related to changes in their life-style. However, although not statistically significant, women who used estrogen without progestin for 12 or more months had an OR of 2.552 (CI 0.231-28.192), while those who used estrogen with progestin for 12 or more months had an OR of 0.425 (CI 0.086-2.113). These results indicate that the addition of a progestin should be considered for reducing the risk of endometrial cancer in Japanese women. PMID- 11770186 TI - Vaginal symptoms in Japanese postmenopausal women: comparison with other climacteric symptoms. AB - OBJECTIVES: This study was designed to investigate the current status of vaginal symptoms in Japanese postmenopausal women, and to clarify the significance of vaginal symptoms by analyzing their relationship to other climacteric symptoms. METHODS: The complaints of 613 women attending a menopause clinic (mean age +/- standard deviation 53.5 +/- 7.2 years; time since menopause or bilateral oophorectomy 6.4 +/- 6.5 years) were evaluated according to the Keio modified menopause index. RESULTS: In total, 56.4% of subjects had at least one vaginal symptom. The most frequent vaginal symptom was dyspareunia, followed by vaginal dryness, discharge and itching, and the mean prevalence of the four symptoms was 31.7%. The peak intensity of vaginal symptoms occurred in the sixth decade, or 3 5 years after menopause or oophorectomy. Vaginal symptoms were usually associated with other climacteric symptoms, but some occurred independently. CONCLUSIONS: A moderate proportion of Japanese postmenopausal women experience vaginal symptoms, which can occur independently of other climacteric symptoms. Vaginal symptoms therefore warrant careful attention during the treatment of postmenopausal women. PMID- 11770187 TI - Attitudes of middle-aged women to aging: contribution of the Reactions to Aging Questionnaire. AB - Attitudes to aging in mid-life have been found to be a predictor of health and well-being. The main purpose of the study was to assess the contribution of the Reactions to Aging Questionnaire (RAQ) to the understanding of middle-aged women's attitudes towards their aging. An additional purpose was to expand the existing information regarding the dimensions of the new version of the RAQ. Middle-aged Melbourne women (n = 381) were asked to complete the RAQ, in addition to another attitudes-to-aging scale (Worries About Aging). Factor analysis of the RAQ was used to explore its dimensionality, and frequencies of responses were used to assess the spread of response of both instruments. The factors extracted in the factor analysis of the RAQ were interpretable and meaningful in terms of emotions related to aging. They were also similar to the factors described by previous data. The RAQ was more effective in its distribution ability than the Worries About Aging Scale. With some modifications, the RAQ may be more informative than was the Worries About Aging Scale in its ability to assess emotions, opinions and beliefs associated with aging in middle-aged women. PMID- 11770188 TI - Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy. AB - OBJECTIVE: The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women. METHODS: Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale. RESULTS: Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse. CONCLUSIONS: The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT. PMID- 11770189 TI - Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. AB - OBJECTIVE: To compare the effects of the selective estrogen receptor modulator (SERM) raloxifene (Evista) and a continuous combined hormone replacement therapy (ccHRT) formulation containing estradiol and norethisterone acetate (Kliogest) on lipid and fibrinogen levels of postmenopausal women. METHODS: Euralox 1 was a prospective, randomized, double-blind trial. After a placebo wash-out, healthy postmenopausal women (n = 1008, average age 56.1 +/- 4.9 years) with a health risk profile that suggested a potential benefit from either treatment were randomly assigned to either 60 mg raloxifene or ccHRT consisting of 2 mg estradiol and 1 mg norethisterone acetate (NETA) per day for 6 months. MEASUREMENTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol with its fractions HDL2 and HDL3, the LDL/HDL ratio, triglycerides and fibrinogen were assessed at baseline and after 6 months or on early drop-out. RESULTS: Baseline values were comparable between the two groups. Blood samples of 841 women (83.4%) were available at baseline and endpoint. Total and LDL cholesterol decreased statistically significantly from baseline to endpoint in both treatment arms (by 7.2% and 3.8% with raloxifene and by 13.0% and 8.9% with ccHRT, respectively). Raloxifene produced a statistically significant increase in HDL cholesterol by 4.2%, while ccHRT induced a decline by 9.5%. Triglycerides were moderately suppressed with raloxifene and ccHRT, by 3.6 and 5.4%, respectively. Fibrinogen fell by 7.0% with raloxifene and rose by 3.6% with ccHRT. CONCLUSIONS: Continuous combined HRT was associated with decreases in total cholesterol and LDL cholesterol about twice as large as with raloxifene, but also with a decrease in HDL cholesterol. The smaller decreases in total cholesterol and LDL cholesterol associated with raloxifene were accompanied by an increase in HDL cholesterol and a decrease in fibrinogen. In conclusion, raloxifene affects fibrinogen concentrations and the overall cholesterol profile more favorably than ccHRT; these differences may have important implications for the reduction of cardiovascular disease. PMID- 11770190 TI - Climodien (estradiol valerate 2 mg plus dienogest 2 mg) is safe and effective in the treatment of postmenopausal complaints. AB - OBJECTIVE: To evaluate the efficacy, safety and tolerability of continuous combined hormone replacement therapy (HRT) with Climodien (estradiol valerate 2 mg plus dienogest 2 mg). DESIGN: Open, multinational, multicenter, non-controlled phase III study. PARTICIPANTS: A total of 1501 women aged 52-65 years with postmenopausal symptoms of sufficient severity to require treatment. METHODS: Eligible patients were treated with Climodien for 12 treatment cycles (48 weeks), with assessments of efficacy, safety and tolerability (adverse events) at 8, 24 and 48 weeks. Efficacy was assessed using the Kupperman index. Safety assessments included endovaginal sonography, safety endometrial biopsies, mammography, physical and gynecological examination, vital signs, prothrombotic factors and routine laboratory safety parameters. RESULTS: The Kupperman index improved with increasing duration of treatment, accompanied by an improvement in self-reported patient well-being. Individual climacteric symptoms such as hot flushes and psychonervous disorders also improved. The most pronounced improvement was seen in women who had not previously used HRT. The incidence of breakthrough bleeding declined over time, resulting in complete amenorrhea in 86.2% of the patients after 12 cycles of treatment. Furthermore, total and low-density lipoprotein (LDL) cholesterol levels decreased and high-density lipoprotein (HDL) cholesterol levels increased. Decreases in alkaline phosphatase, pyridinoline and deoxypyridinoline demonstrated the inhibitory action of estradiol on bone resorption. Endometrial thickness remained almost constant, and the incidence of serious endometrial findings was similar to that in untreated women. CONCLUSIONS: Continuous combined estrogen-progestin therapy with Climodien is effective, safe and well tolerated in postmenopausal women, with a profile and incidence of adverse events consistent with those of existing HRT preparations. PMID- 11770191 TI - Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate. AB - OBJECTIVE: This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms. METHODS: The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study. RESULTS: All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group. CONCLUSION: All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern. PMID- 11770192 TI - Aretaeus on migraine and headache. AB - Aretaeus of Cappadocia's classification of headache has been referred to for many centuries. Several Latin translations and an English translation (1856) of his books have been published in the past. We translated the pertinent texts on headache from the Greek text as published by Hude in 1958. In this paper, we present an annotated translation preceded by an outline of contemporary knowledge of headache from Celsus' De Medicina. Although symptomatic headache was most probably involved in the types of headache identified by Aretaeus and the making of retrospective diagnoses is hazardous, the terms heterocrania and cephalea may be compared with what today we would call migraine and tension type headache respectively. PMID- 11770193 TI - Biological and epistemological models of localization in the nineteenth century: from Gall to Charcot. AB - In the latter half of the nineteenth century, the localizationist doctrines became closely associated with the memory trace paradigm. The analysis of the texts dealing with the localization and the nature of 'the loss of articulated speech' (motor aphasia) by Bouillaud, Lordat, Dax, Broca, Trousseau, Baillarger, Charcot and Wernicke shows how the biological paradigm of localization presented by Gall and based on the notion of organ-function correspondence was transformed into a model based on localizable memory traces. This change resulted in the theoretical unification of the mechanisms of motor and non-motor forms of aphasia. These forms, which the earlier authors tended to separate in their analyses of the underlying mechanisms, were now regarded as involving similar mechanisms related to the loss of mnestic images. The crucial step in this development was taken by Broca who presented the hypothesis that the faculty of coordination of speech movements, which according to his predecessors was the faculty lost in motor aphasia, was actually an intellectual faculty and a specific form of memory, and motor aphasia consequently a selective kind of amnesia. Theorists like Charcot and Wernicke generalized this idea into a comprehensive theory of the nature of localization based on the notion of memory traces. Thus, the localization of function was reduced to the localization of representations. Instead of biological paradigms, this model of localization is rooted in the epistemological tradition of psychology represented by Locke and Condillac, who were primarily interested in the problem of representation. In physiology, this approach usually resulted in attempts at localizing representations instead of functions. PMID- 11770194 TI - Facts and philosophy in neurophysiology. The 200th anniversary of Johannes Muller (1801-1858). AB - Johannes Muller was the founder of the first school of physiology in Germany. His anatomical, morphological and physiological research as well as his epistemological view of scientific medicine opened the way to a deeper understanding of the structure and the function of the organism. With important discoveries like the law of sense energy, the reflex movement and the definition of different organic stimuli, he enriched the knowledge of neuroanatomy, neurophysiology and sensory physiology and smoothed the way to an experimental physiology. All his famous students like Hermann von Helmholtz, Emil Du Bois Reymond, Ernst Brucke, Jakob Henle, Robert Remak, Rudolf Virchow and Ernst Haeckel solved many crucial research problems, which Muller identified and pointed out to them as open questions, due to the insufficient methods of investigation. Muller's research method, epistemological view of biological sciences, and his open-minded personal style encouraged the development of new methods adapted to particular problems. PMID- 11770195 TI - William Alexander Hammond: the centenary of his death. AB - In the United States, the field of clinical neurology began within the medical practice of a single physician, William Alexander Hammond. In the 1870s, this New York medical practitioner became the first American physician who limited his practice to patients who suffered from symptoms potentially due to dysfunction of the nervous system. From the experience of his huge practice, Hammond wrote the first American textbook of neurology. With Silas Weir Mitchell, he founded the American Neurological Association. The year 2000 marked the 100th anniversary of Hammond's death and stimulates this brief survey of his life. PMID- 11770196 TI - Ludwig Guttmann: emerging concept of rehabilitation after spinal cord injury. AB - Ludwig Guttmann was a pioneer of the idea of rehabilitation for victims of spinal cord injury. He looked beyond the physical survival of his patients, to their re integration into a social life worth living. While the International Stoke Mandeville Games are fairly well known to the general public as a gathering for physically handicapped athletes, less is known about the man who helped start the movement. On the occasion of the recent Sydney 2000 Paralympics, this paper reviews the contribution of Ludwig Guttmann, who introduced sport into the life of paralyzed patients. PMID- 11770197 TI - Fifty years since Lashley's In search of the Engram: refutations and conjectures. AB - In his well-known article 'In Search of the Engram' published in 1950, Karl Spencer Lashley summarized his 33 years of research and theory on memory and the brain. He concluded that (1) memories are not localized but are instead distributed within functional areas of the cortex and (2) memory traces are not isolated cortical connections between inputs and outputs. Though not the first time he had expressed such convictions, their reiteration in this article was backed by Lashley's estimable reputation and expressive power and they have taken firm root in the collective knowledge of today's memory and neuropsychological research community. PMID- 11770198 TI - The man behind the skull. PMID- 11770199 TI - Claustrum: a sea wall between the island and the shell? PMID- 11770200 TI - Growth performance and reproductive traits at first parity of New Zealand white female rabbits as affected by heat stress and its alleviation under Egyptian conditions. AB - Exposing growing and adult New Zealand White (NZW) female rabbits to severe heat stress (temperature-humidity index = 28.9) during summer adversely affected their growth and reproductive traits. The traits that declined significantly (p < 0.01) were the live body weight, daily weight gain and feed intake of growing rabbits, and the litter size and litter weight at weaning (p < 0.05) and the pre-weaning weight gain of pups (p < 0.01) for adult females. The conception rate declined considerably with heat stress. The declines in the values of the digestibility coefficients due to heat stress were 7.9% (p < 0.05) for dry matter (DM), 8.1% (p < 0.05) for crude protein (CP) and 1.0% for crude fibre (CF). The traits that increased significantly (p < 0.01) due to heat stress were water intake, water/feed ratio and rectal temperature in growing rabbits and pre-weaning mortality for adult females. Alleviation of heat stress in the growing and adult female NZW rabbits was more efficient with drinking cool water (10-15 degrees C; between 10:00 and 17:00) than with supplementation with palm oil (as a source of energy) or natural clay (as a natural enhancer to growth and milk production). Supplying the animals with cool drinking water gave the highest body weight and weight gain, conception rate, litter size and weight and digestibility coefficients for DM and CP and the lowest rectal temperature, respiration rate and pre-weaning mortality. The loss in rabbit production pertaining to heat stress estimated from the percentages of decline in conception rate x pre-weaning mortality x litter weight at weaning was 73.0%. The provision of cool water restored 11/12 of heat loss. PMID- 11770201 TI - Bovine mastitis due to Prototheca zopfii: clinical, epidemiological and pathological aspects in a Brazilian dairy herd. AB - The clinical, epidemiological and pathological aspects of protothecal mastitis in a Brazilian dairy herd are described. Prototheca zopfii infection was diagnosed in 11 of 121 milking cows. Clinical mastitis refractory to usual therapy was observed in 7 cows. Several environmental conditions conducive to the growth of Prototheca spp., such as wetness, muddiness and the presence of organic material, were present in the dairy. Improper milking practices and insanitary infusion of the intramammary antibiotics were also observed. Six cows with protothecal mastitis were slaughtered and the affected quarters of each cow were examined by histology and immunohistochemical staining for bovine keratin and P. zopfii. The histological lesions were characterized by interstitial infiltrates of macrophages, plasma cells and lymphocytes; algae were seen in the alveolar lumen and interstitium. The lack of a positive reaction with an antiserum against bovine keratin in the mammary alveolar epithelial layer in some affected areas suggests destruction of milk-producing tissues, which may be related to the low milk production observed. The algal organisms stained positively with a polyclonal antibody against P. zopfii. PMID- 11770202 TI - Ovine lentivirus is aetiologically associated with chronic respiratory disease of sheep on the Laikipia Plateau in Kenya. AB - A study was undertaken to investigate the occurrence of ovine lentivirus (OvLV) infection in sheep with chronic respiratory disease on the Laikipia Plateau, Kenya. All seven Merino crossbred sheep with chronic dyspnoea and emaciation examined for gross and microscopic lesions had lymphoid interstitial pneumonia (LIP), and one also had pulmonary abscesses. Two of the sheep with LIP also had lesions of ovine pulmonary carcinoma (OPC, jaagsiekte). Using in situ hybridization, OvLV DNA localized to a high proportion of pulmonary macrophages in lungs with lesions of LIP. Lung tissue samples from six of these sheep were positive for a syncytium-inducing virus in cultures of lamb testis cells. Thin section electron microscopy of infected cells showed virions with morphogenesis typical of lentiviruses. In a western blotting assay, monoclonal antibodies to the OvLV capsid (CA, p27) and matrix (MA, p15) proteins of a North American OvLV isolate reacted with similar-sized bands of the virus, and serum from six of the sheep were reactive with CA from the Kenyan viral isolate. Using an OvLV agar gel immunodiffusion (AGID) test, all seven sheep were positive for serum antiviral antibody, as were 29% of 63 clinically normal sheep from Laikipia District. However, when sera from the healthy sheep were tested in a western blot assay, only 52% had IgG reactive to the OvLV CA, indicating a high rate of false negative reactions with the AGID test. Serum samples from 87 Red Maasai or Dorper crossbred sheep from two farms in other parts of Kenya were OvLV seronegative by both the AGID test and the western blot assay. These results document the first identification of OvLV as a cause of chronic respiratory disease in sheep in Kenya and show a high rate of infection in sheep flocks, with a high prevalence of chronic respiratory disease. PMID- 11770203 TI - Studies on Cephalopina titillator, the cause of 'Sengale' in camels (Camelus dromedarius) in semi-arid areas of Somali State, Ethiopia. AB - The overall prevalence rate of Cephalopina titillator in 778 slaughtered camels was 71.7%, 55% in males and 85% in females. The mean larval counts in infested camels were 26.7 +/- 25.9 and 34.6 +/- 30.8, for males and females, respectively. There were highly significant differences (p < 0.001) in the number of larvae in camels of different ages and sexes and also between the wet and dry seasons. The average time to pupate was 4.9 +/- 4.6 minutes, and the pupation period was 21 +/ 2.4 days. The major gross lesions observed were congestion of the pharyngeal mucosa with profuse secretions, and haemorrhage in early cases. In some cases, there were ulcer-like lesions and nodules, which contained pus. The dominant microscopic lesions were infiltration of the lamina propria by eosinophils, lymphocytes and macrophages, hyperplasia of the stratified squamous epithelium, necrotic changes in the mixed glands and desquamation of epithelial cells. A survey using questionnaires revealed that all the camel owners called the disease caused by infestation with C. titillator 'Sengale' and that 87% of them considered that infestation with these larvae results in reduced milk production and body weight. The major clinical signs of the disease were sneezing and expulsion of larvae (68%), abnormal movement of the head (45%), grooming (44%), nasal discharge (40%), poor appetite (26.7%), difficulty in breathing (18%), and sometimes bleeding from the nostrils (18%) and coughing (27%). PMID- 11770204 TI - Seasonal variations in the abundance of Gasterophilus spp. larvae in donkeys in northern Jordan. AB - One hundred and five donkeys were examined over a 12-month period for the presence of Gasterophilus spp. larvae in their stomachs. G. intestinalis and G. nasalis were found, but there was a distinct seasonal variation in their abundance. The numbers of second-stage larvae (L2) peaked during the early winter and early summer, but they were absent or at low levels during the early spring and early autumn. This suggests that there are two periods of adult fly activity (late autumn and late spring) for both G. nasalis and G. intestinalis. Third stage larvae (L3) were found throughout the year, but the lowest levels were seen in the late summer and autumn. The parasites also had an aggregated distribution, which may be due to host selection by the fly. The numbers of larvae did not vary significantly with age, which may be due to a lack of acquired protective immunity or to tolerance after repeated exposure. PMID- 11770206 TI - Village poultry production systems in the central highlands of Ethiopia. AB - Participatory rural appraisal (PRA), supported by checklists and intensive case studies on individual households, was carried out in three villages at three different altitudes in the central highlands of Ethiopia. The chicken production system in each village is described and the problems are discussed. More than 60% of the families kept chickens, and in most cases the women owned and managed the birds and controlled the cash from the sales. The production systems followed were mainly low-input and small-scale, with 7-10 mature birds per household, reared in the back yards with inadequate housing, feeding and health care. The average egg production per clutch was 15-20, with 3-4 clutches per year. The mean number of eggs set per bird was 12.9 +/- 2.2 (n = 160), depending on the size of the bird and season, and the hatching rate was 80.9% +/- 11.1%, range 44%-100% (n = 160). Poultry meat and eggs were generally accepted and appreciated in all three villages. In addition to the small amount of cash income they provide, scavenging chickens have nutritional, cultural and social functions. The flock composition, price of poultry and poultry products, disease outbreaks and hatching of chicks were strongly affected by season. Disease was cited as the most important problem by most of the members of the community, followed by predation, lack of feed, poor housing, insufficient water and parasites. Disease periodically decimated the flocks, and consequently, about 50% of the eggs produced were incubated in order to replace the birds that had died. The major source of loss in the system was the high mortality of chicks (61%) that occurred between hatching and the end of brooding at 8 weeks of age. The system was characterized by no or few inputs and a low output level. The major input was the cost of foundation stock, but after that virtually no cost was involved. The major source of feed for the birds was from the scavenging feed resource base, which comprised table leftovers, small grain supplements and anything edible from the immediate environment. PMID- 11770205 TI - Treatment trial of subclinical mastitis with the herb Persicaria senegalense (Polygonaceae). AB - The possible remedial effect of Persicaria senegalense in bovine subclinical mastitis was studied by in vitro and in vivo antimicrobial tests, using crude extracts and the leaf in different forms. The in vitro test showed that isolates of Staphylococcus aureus, Candida albicans and Corynebacterium bovis from subclinical cases and an isolate of Pseudomonas aeruginosa from a clinical case of mastitis were all inhibited by the three crude extracts at 820 micrograms concentration. An in vivo trial feeding 1.5 kg of the cooked leaf per day for 5 days did not give a significant cure rate, whereas a second trial in which 0.77 kg of leaf powder, equivalent to 3 kg of wet leaf, was fed per day for 5 days resulted in an apparent cure rate of 92.8% (52.8% actual as there was a 40% spontaneous cure rate in the negative control group, in contrast to 80% (40% actual) in the positive control group treated with an intramammary antibiotic preparation. The difference in cure rate between the negative control group and the experimental group given 0.77 kg leaf powder was significant (p = 0.008). PMID- 11770207 TI - Health Status measurement: an increasingly important outcome evaluation in COPD patients. PMID- 11770208 TI - Reported diagnosis of previous asthma in a sample of the Italian general population. AB - In this cross-sectional study we describe the prevalence and characteristics of subjects who self-reported a diagnosis of previous asthma in a sample of the Italian general population. We chose a wide age range (3-69 yrs) in order to obtain data over a large spectrum of the population. Interviews were conducted in 1,038 subjects by trained physicians using a modified version of the American Thoracic Society and National Heart & Lung Institute--Division of Lung Disease questionnaire proposed in 1978 (ATS-DLD-78). 791 subjects underwent skin prick tests for 7 common aeroallergens; 422 subjects underwent spirometry and 212 methacholine challenge tests. Cumulative prevalence of asthma was 7.9% (82/1038). Previous asthma (PA) was reported by 29 (35.4%) of the subjects, who said they had been but were no longer asthmatic; 65.5% of these claimed that PA had developed at or before the age of 14 yrs. No significant differences emerged in sex, age, family and personal history of atopy, and size of skin test reaction in subjects with PA compared to those with current asthma (CA). Although the difference was not statistically significant, the latter tended to be lifetime nonsmokers while subjects with PA were more often current smokers. Age at onset of asthma was significantly higher in subjects with CA than in subjects with PA (24.6 +/- 20 yrs vs. 12.0 +/- 15.0 yrs, p = 0.005). Bronchial hyperreactivity was present in 37.5% of subjects with PA, while forced expiratory volume in 1 sec (FEV1) was within normal limits in all. In conclusion, in this sample of the Italian population, PA was reported by about 1/3 of the asthmatic subjects, most of whom were atopic. Lung function was within normal limits in all, but bronchial hyperreactivity persisted in 1/3 subjects. PMID- 11770209 TI - Atopy prevalence and spirometric performance in asymptomatic schoolchildren exposed to air pollution. AB - The association between respiratory disease and high levels of air pollution is well known. The most common risk factors associated with lung function decrease are air-borne particulates, ozone (O3), nitrogen dioxide (NO2) and sulphur dioxide (SO2). The aim of our study was to evaluate any difference in the prevalence of atopy and any possible early impairment in lung function in two groups of children exposed to different levels of air pollution. We studied 220 children in two cities in northern Italy: Milan (107 children), considered a metropolitan area with a high level of air pollution, and Erba (113 children), a small town, close to Lake Como, considered a rural area with a low level of air pollution. All subjects underwent respiratory function tests and skin-prick tests for the main inhalatory allergens. Parents were requested to fill in a questionnaire about parents' smoking habits and subjective evaluation of local motor traffic intensity. Aerobiological surveys showed a significantly higher grass pollen concentration in Erba than in Milan in the study year and in the three previous years. Schoolchildren in Milan and Erba showed similar pulmonary function results, except for forced expiratory flow at 75% of forced vital capacity (FEF75) values that, while within the range of normality, were significantly lower in Milan than in Erba. A high incidence of atopy was evident in both groups: 45% among the children living in Erba and 35% among those in Milan; skin-prick-test positivity for grass-pollen was statistically more frequent in Erba than in Milan. No evidence of a link between atopy and FEF75 reduction emerged, nor between FEF75 reduction and exposure to passive smoke. The association between FEF75 reduction and chronic high levels of air pollution is appealing, but further confirmation studies are necessary. PMID- 11770210 TI - Relationship between pulmonary function and unsupported arm exercise in patients with COPD. AB - In patients with chronic obstructive pulmonary disease (COPD) the limitation on unsupported arm exercise (UAE) is predominantly respiratory muscle function dependent. It is characterized by neuromechanical dysfunction (thoracoabdominal dyssynchrony) of the inspiratory muscles (diaphragm, accessory), superimposed by lung mechanics dysfunction. The undergoing mechanism is probably multifactorial. To study the relationship of resting pulmonary function and UAE performance in patients with COPD. Twenty-one patients, mean age 63 +/- 7 years, with COPD [forced expiratory volume in the first second (FEV1) 42 +/- 12% of predicted] underwent assessment of resting lung function (inspiratory capacity 57 +/- 17%; functional residual capacity 204 +/- 38% of predicted), maximal inspiratory pressure (67 +/- 14 cmH2O), upper arm circumference (30 +/- 2 cm), and symptom limited cardiopulmonary UAE assessments. UAE consisted of bilateral anterior arm elevation to shoulder level at a rate of 40 arm strokes.minute-1. A series of stepwise multiple regression models were fitted to the data to predict exercise time from resting pulmonary function indices. RESULTS: Statistically significant correlations (r) were found between exercise time and inspiratory capacity (% of predicted) (r = 0.67, p = 0.0008), maximal inspiratory pressure (cmH2O) (r = 0.47, p = 0.03), upper arm circumference (r = 0.74, p = 0.0001), FEV1 (% of predicted) (r = 0.62, p = 0.0026), oxygen uptake (r = 0.56, p = 0.0085) and functional residual capacity (% of predicted) (r = -0.41, p = 0.06, borderline). Inspiratory capacity (% of predicted), functional residual capacity (% of predicted), upper arm circumference (cm) and FEV1 (% of predicted) explained 77% of the variance in exercise time. Therapeutic strategies that aim to increase inspiratory capacity or decrease functional residual capacity, or increase inspiratory muscle strength and upper arm/torso muscle endurance are likely to alleviate symptoms and improve UAE performance in patients with COPD. PMID- 11770211 TI - Tuberculosis of oral mucosa. AB - In secondary tuberculosis, lesions of the oral cavity may accompany lesions of the pharynx, lungs, lymph nodes or miliary tuberculosis. A 35-year-old male was suffering from swelling of his right cheek, cough, weakness and weight loss. There were local hyperemia and irregular oral mucous in the inner part of the right cheek. Chest x-ray showed bilateral nodular opacifications and a cavity of 2 cm. Acid-fast bacteria were present in sputum and Lowenstein-Jensen culture was positive. The pathological signs of the biopsy taken from the buccal mucosa including multistratified squamous epithelium were: tubercle structure, Langhans' giant cells and minimal cazeation necrosis. After anti-tuberculous chemotherapy oral and pulmonary lesions were almost in remission. Following this case report of lung tuberculosis accompanied by tuberculosis of oral mucosa, the literature related is reviewed. PMID- 11770212 TI - Tracheal stenosis due to brachiocephalic artery aneurysm successfully treated with stenting. AB - Tracheal stenosis secondary to an aneurysm of the great vessels is a rare presentation, previously thought to be unremediable to tracheal stenting. The introduction of covered, expandable, metallic stents has led to the successful treatment of a patient with tracheal stenosis secondary to an aneurysmal brachiocephalic artery without resorting to major cardiothoracic surgery. PMID- 11770213 TI - Tracheal stenting for rupture of the posterior wall of the trachea following percutaneous tracheostomy. AB - Perforation of the posterior wall of the trachea during percutaneous tracheostomy is a recognised complication. Treatment by either conservative or surgical management has been described. We report two patients who developed posterior tracheal wall perforation following percutaneous tracheostomy who were successfully treated by insertion of covered, expandable metallic stents. This is a well tolerated procedure that has minimal complications and can be performed at the bedside. We recommend that tracheal stenting should be considered for the management of posterior tracheal wall perforation following percutaneous tracheostomy in those patients unsuitable for surgical intervention. PMID- 11770214 TI - External modulation of airway narrowing. AB - Compelling evidence has been provided in the last decade that deep inspirations potently attenuate the response to contractile stimuli of normal but not of asthmatic airways. Though it is generally accepted that the modulating effect of deep inspirations on airway narrowing is based on the interdependence between airways and lung parenchyma, the intimate mechanisms are still the object of active research. In this paper, the practical relevance of the reduced ability to dilate airways with deep inspirations will be discussed. PMID- 11770215 TI - Pathophysiology of dyspnea. AB - Dyspnea may be defined as an uncomfortable sensation of breathing. The sense of respiratory effort, chemoreceptor stimulation, mechanical stimuli arising in lung and chest wall receptors, and neuroventilatory dissociation may all contribute to the sensation of dyspnea. Different mechanisms likely give rise to qualitatively different sensations of dyspnea. In most patients, dyspnea is probably due to a combination of mechanisms. For example, in asthma, a heightened sense of effort, neuroventilatory dissociation, and vagal stimuli arising from bronchoconstriction and airway inflammation may all play a role. Patients with different disorders and different mechanisms of dyspnea use different phrases to describe their breathing discomfort. Hence, the language patients use to describe their dyspnea may provide clues to the etiology of their symptoms. PMID- 11770216 TI - Non-pulmonary factors affecting survival in patients completing pulmonary rehabilitation. AB - Patients referred to pulmonary rehabilitation usually have advanced chronic obstructive lung disease (COPD). This disease is a common cause of death in developed countries, ranking fourth as a cause of death in the United States, behind heart disease, cancer, and stroke. The three-year survival following outpatient pulmonary rehabilitation is approximately 80%. Clearly, markers of disease severity such as the degree of airways obstruction, arterial blood gas abnormality, degree of pulmonary hypertension, and the need for hospitalizations predict mortality in this disease. However, because of substantial co-morbidity, patients with COPD often die with their disease rather than from their disease. Thus, only 45 to 63% of deaths in patients with advanced lung disease are directly due to the disease itself. Factors other than primary disease severity that predict mortality in COPD include nutritional depletion, exercise endurance, functional performance, and even social factors such as marital status. Thus, once the chronic lung disease progresses to the point where referral is made to pulmonary rehabilitation, non-pulmonary factors are also important predictors of survival. This underscores the importance of a holistic approach to the patient with advanced lung disease, and the need for a comprehensive severity grading system that includes more than the forced expiratory volume in 1 sec (FEV1). PMID- 11770217 TI - Economic analyses and lung cancer. AB - The economic assessment of treatments or medical strategies has been the subject of an increasing number of publications. The elevated costs and relative lack of efficacy of many treatments of chronic diseases such as lung cancer are an added impetus to such analyses. In the first part of this review, we summarise the theoretical basis of economic assessment, the tools available and the limitations of these methods. In the second part, we examine their application to the treatment of lung cancer. We discuss the evaluation of the cost of these cancers to society, economic assessment of new chemotherapeutic drugs, and the place of cost-effectiveness analysis in randomized trials. In the last part, we outline the interest and future of such considerations for clinicians. These methods, which provide complementary data for clinicians when making decisions on therapeutic options, will be adopted more widely in coming years. PMID- 11770218 TI - Management of primary spontaneous pneumothorax: does cause matter? AB - The best treatment of primary spontaneous pneumothorax is unknown. Since no prospective, randomised comparative studies between various treatment strategies, and only a few between various therapeutic techniques, are available today, the choice of treatment varies widely between specialties (pulmonologists versus surgeons), institutions, countries, and continents. In this paper, an overview of the current therapeutic approaches with respect to the underlying cause of primary spontaneous pneumothorax is provided. PMID- 11770219 TI - Cigarette smoking and asthma. AB - Cigarette smoking is a well-know health hazard, probably not least for patients suffering from asthma. This review gives a short overview concerning the effects of passive and active smoking on the inception and outcome with regard to longitudinal changes in lung function and mortality for patients with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke in children, especially maternal smoking, may be a significant risk factor for asthma. Environmental tobacco exposure in patients with established asthma is not only associated with more severe symptoms, but also with lower quality of life, reduced lung function, and increased health care utilisation for asthma, including hospital admissions. Active smoking appears not to be a significant risk factor for asthma, but it is associated with worse outcome with regard to both longitudinal changes in lung function and asthma related mortality. Based on the current knowledge, it therefore seems of utmost importance to encourage patients with asthma not to smoke. In line with this, patients with asthma should be given full support in their right to a smoke-free environment. PMID- 11770220 TI - First report of the Italian register for diffuse infiltrative lung disorders (RIPID). AB - RIPID was established in 1998 as a joint project of the major Italian scientific societies for Respiratory Medicine, with the aim to create an Italian Register on diffuse infiltrative lung disorders that can provide the basis for epidemiological and clinical studies of adequate sample size. In the period from May 1998 to December 2000, 1,382 cases were submitted from 54 Centers in 15 regions of Italy, 54.2% males (mean age +/- SD 50.5 +/- 16.8 years) and 45.8% females (50.2 +/- 15.3 years). A current smoking habit emerges in 18% of subjects; former smokers and never-smokers represent 26% and 56% of the total case series, respectively. The most frequent disease registered is idiopathic pulmonary fibrosis (37.6%), followed in decreasing order by sarcoidosis (29.2%), and Langherans' cell hystiocytosis (6.6%). High resolution computed tomography (HRCT) was considered as the most important tool for final diagnosis in the majority of cases (74.4%); 39.4% of patients underwent transbronchial biopsies, 39.2% bronchoalveolar lavage (BAL). A surgical biopsy was performed in 20.5% of patients. A web site has been activated from December 2000 (www.pneumonet.it/ripid), allowing prompt access to all information and scientific material concerning the project and to an electronic form for data collection that can be completed on-line. PMID- 11770221 TI - Recent developments in Alzheimer's disease. AB - Alzheimer's disease is the most frequent form of dementia and it is estimated that its prevalence will quadruple by the year 2050. In the past decade, a number of important new developments have provided insight in the pathogenesis, improved diagnosis and allowed therapy of dementia. Several new mutations in the amyloid protein precursor gene, presenilin-1 and -2 genes and the influence of the apolipoprotein E gene isotypes on the disease phenotype have been described. The role of secretases in the generation of amyloid in senile plaques has been determined and this may provide important new therapeutic approaches in the future. The role of vascular lesions in the development of dementia and relationship with the Lewy body variant of Alzheimer's disease have been refined. Acetylcholine is deficient in Alzheimer's disease and can be supplemented in part by treatment with acetylcholinesterase inhibitors. Recently, surprising results of vaccination with amyloid in a transgenic mouse model have opened a completely new perspective in the prevention and treatment of Alzheimer's disease. PMID- 11770222 TI - ACE-inhibitors versus angiotensin receptor blockers for renoprotection: conclusions from the evidence and from the evidence behind the evidence. PMID- 11770223 TI - Implementation of pretravel advice: good for malaria, bad for diarrhoea. AB - Pretravel immunizations and health advice can substantially reduce the incidence of travel-related diseases. The aim of this study was to evaluate the implementation of pretravel advice among a homogenous group of students, who received similar written information on vaccination requirements and health advice. They were referred to the travel clinic (50%) or a general practitioner (50%) for vaccination, counselling and prescriptions. Eighty-four out of 110 students (76%) returned the questionnaire. Insect repellent was used by all and only 10 used the repellent for less than 75% of the time spent in malaria endemic areas. Malaria chemoprophylaxis was taken by all but one: chloroquine plus proquanil by 12 and mefloquine by 71. Reported compliance with the dosing regimen was optimal in 64 students, 9 missed one dose and 10 stopped too early. Side effects due to antimalarials were reported by 25 (30%). Diarrhoea during travel occurred in 43 students (51%). Loperamide was used by 34 students with diarrhoea (79%), but only 2 out of 27 students with moderate to severe diarrhoea used the recommended self-treatment with a fluoroquinolone antibiotic. In conclusion, the recommendations of malaria prophylaxis were well implemented by most travellers despite a high incidence of self-reported side effects to antimalarials. The incidence of traveller's diarrhoea was high and the recommendation for early self treatment of moderate to severe diarrhoea with a fluoroquinolone antibiotic in combination with loperamide was not put into practice. PMID- 11770224 TI - Therapy, glycaemic control and complications in type 1 diabetic patients: results from a single centre cohort of 465 subjects. AB - We analysed the clinical characteristics, the degree of glycaemic control and the prevalence of complications in 465 type 1 diabetic adult patients (232 males), in view of current recommendations for metabolic and blood pressure control. Age and diabetes duration were 45 +/- 17 and 20 +/- 13 years respectively (mean +/- 1 SD). Daily insulin dose was 0.65 +/- 0.24 U/kg b.w. 73% of patients received > or = 3 injections/day, while 11% had continuous subcutaneous insulin infusion. All were practicing home blood glucose monitoring. Current HbA1c was 8.5% [7.7-9.3%] (median [percentiles 25-75]). There was no difference in HbA1c according to number of injections or CSII use. When patients were divided according to HbA1c quintiles, significantly lower prevalences of retinopathy and neuropathy were found in quintile 1 individuals. A mean of 53 severe hypoglycaemic episodes was reported per 100 patients/year, and they were more frequent in subjects exhibiting better glycaemic control. High blood pressure levels were found in 27% of subjects according to JNC-VI criteria. Fasting cholesterol (C), LDL-C, HDL-C and triglycerides were within normal range. However, according to current guidelines emphasizing on lower target thresholds, up to 27% of patients exhibited some degree of dyslipidaemia, in particular LDL-C higher than 3.3 mmol/l. In conclusion, in this large cohort of type 1 diabetic patients regularly attending a University Centre, overall glycaemic control remains above the satisfactory levels inferred from optimization studies. Although mean blood pressure and blood lipids were up to recently deemed adequate, a (too) high proportion of diabetic patients exhibited either hypertension and/or dyslipidaemia according to revised therapeutic goals cut-offs. PMID- 11770225 TI - Distribution and prevalence of antimicrobial resistance among gram-negative isolates in intensive care units (ICU) in Belgian hospitals between 1996 and 1999. AB - OBJECTIVE: To assess the distribution and prevalence of resistance rates among Gram-negative isolates in Belgian intensive care units (ICUs) between 1996 and 1999. METHODS: During 1996-1997 and 1998-1999, over a total period of 10 and 9 months respectively, members of the NPRS Belgian Study group collected, on clinical indications, 3029 consecutive initial isolates of Gram-negative bacteria from patients admitted to 26 Belgian hospitals and performed minimal inhibitory concentration (MIC) determinations by means of the E-test. Break-points were defined according to the criteria of the NCCLS. RESULTS: The overall distribution of bacterial species was, in decreasing order of frequency: Pseudomonas aeruginosa > E. coli > E. aerogenes > K. pneumoniae > P. mirabilis > S. marcescens > E. cloacae > K. oxytoca > M. morganii > Stenotrophomonas maltophilia > Acinetobacter spp. All together these species and genera constituted about 90% of all isolates. The frequency of resistance for all the initial Gram-negative isolates in 1998-9 were: amoxicillin-clavulanic acid 60%, piperacillin 31%, piperacillin-tazobactam 20%, cefuroxime 58%, ceftriaxone 31%, ceftazidime 17%, aztreonam 23%, cefepime 10%, imipenem 13%, gentamicin 12%, amikacin 12% and ciprofloxacin 21%. Apart for an increase in multiple drug resistance among P. aeruginosa isolates, no significant trends were observed neither in species distribution nor in the overall prevalence of antimicrobial resistance among Gram negative isolates from Belgian ICUs between 1996-7 and 1998-9. CONCLUSIONS: Among Gram-negative isolates in Belgian ICUs, a very high frequency of resistance was seen to amoxicillin-clavulanic acid and cefuroxime, and rather high frequencies of resistance to piperacillin, ceftriaxone and aztreonam. Taking into account the species distribution and the prevalence of resistance, cefepime, imipenem, amikacin and gentamicin appeared generally suitable for empirical therapeutic use in severe ICU-acquired Gram-negative infections in Belgium. However, the therapeutic strategy should be adapted according to the local ecology of resistance. PMID- 11770226 TI - Recombinant humane thyrotropin (rhtSH) a new aid in the diagnosis and treatment of thyroid carcinoma with radio-iodine. AB - By example of two cases a newly available tool, the recombinant humane thyroid stimulating hormone (rhTSH) is discussed in its use as an adjunct in diagnosing and treating differentiated thyroid carcinoma with radio-iodine. This product is an easier and safe alternative to the necessary rise of TSH induced by thyroid hormone withdrawal and concurrent hypothyroidism. Although discrepancies in favour of the classical approach have been demonstrated in some patients, the clinical relevancy of these must be weighted against the advantage of avoiding undesirable symptoms and possible tumour growth by the use of rhTSH. The role of rhTSH in the follow-up diagnosis and radioiodine treatment of thyroid carcinoma will undoubtedly increase in importance. PMID- 11770227 TI - Burkitt's lymphoma shortly after an acute HIV infection, treated with highly active retroviral treatment. PMID- 11770228 TI - Digital x-ray systems. Part 2. An overview of digital radiography concepts and an evaluation of cassetteless DX systems. AB - In this article, we conclude our two-part series on digital x-ray (DX) systems, which we began in our August 2001 issue. Part 2 includes an overview of some important digital radiography concepts, as well as the results of our testing of three cassetteless DX systems. The Technology Overview discusses new radiographic concepts pertaining specifically to DX systems, as well as how established measures of image quality apply to DX technology. These concepts will help buyers objectively compare systems and will help healthcare facilities realize the greatest benefits from digital radiography. Our product testing covers three cassetteless DX systems from three suppliers. We looked at whether these systems provide at least the same amount of diagnostic information as conventional screen film systems while significantly increasing the efficiency of the radiology department and the entire healthcare facility. We rate all the evaluated systems Acceptable but consider two to be superior, based on the overall versatility of one and the user interface of the other. PMID- 11770229 TI - Wireless communication devices and electromagnetic interference. ECRI's updated recommendations. AB - The controversy continues over whether to permit cell phones and other wireless communication devices to be used in hospitals. It's well known that wireless devices emit radio-frequency signals that can cause interference when used in close proximity to medical equipment. But is the risk of interference manageable? Should hospitals allow use of these devices by staff and possibly by members of the public (particularly now that so many people carry a cell phone or some other wireless device)? In October 1999, we recommended that hospitals permit the limited use of cell phones by patients and visitors but restrict the use of walkie-talkies to necessary staff members only. These recommendations still hold. In fact, many of the newer wireless devices--such as wireless personal data assistants, two-way pagers, and family radio service walkie-talkies--operate similarly to a cell phone or a walkie-talkie. Therefore, our recommendations cover them as well. In this Guidance Article, we discuss the reasons for our recommendations. In addition, because we know some hospitals are wrestling with these issues, we provide some useful suggestions for creating and implementing a realistic, effective policy covering the use of wireless technologies in the hospital. PMID- 11770230 TI - Watch your fingers while raising and lowering Glideaway I siderails on Stryker stretchers. PMID- 11770231 TI - Don't tip portable LOX containers. PMID- 11770232 TI - Potential data loss GE Medical Systems Information Technologies MAC PC and MAC 6 resting ECG Analysis Systems. PMID- 11770233 TI - Preventing medical gas mix-ups. PMID- 11770234 TI - Kangaroo Mother Care in very low birth weight infants. AB - OBJECTIVE: This study was conducted (i) to study through a randomized control trial the effect of Kangaroo Mother Care (KMC) on breast feeding rates, weight gain and length of hospitalization of very low birth neonates and (ii) to assess the acceptability of Kangaroo Mother Care by nurses and mothers. METHODS: Babies whose birth weight was less than 1500 Grams were included in the study once they were stable. The effect of Kangaroo Mother Care on breast feeding rates, weight gain and length of hospitalization of very low birth weight neonates was studied through a randomized control trial in 28 neonates. The Kangaroo group (n = 14) was subjected to Kangaroo Mother Care of at least 4 hours per day in not more than 3 sittings. The babies received Kangaroo Care after shifting out from NICU and at home. The control group (n = 14) received only standard care (incubator or open care system). Attitude of mothers and nurses towards KMC was assessed on Day 3 +/- 1 and on day 7 +/- 1 after starting Kangaroo Care in a questionnaire using Likert's scale. RESULTS: The results of the clinical trial reveal that the neonates in the KMC group demonstrated better weight gain after the first week of life (15.9 +/- 4.5 gm/day vs. 10.6 +/- 4.5 gm/day in the KMC group and control group respectively p < 0.05) and earlier hospital discharge (27.2 +/- 7 vs. 34.6 +/- 7 days in KMC and control group respectively, p < 0.05). The number of mothers exclusively breastfeeding their babies at 6 week follow-up was double in the KMC group than in the control group (12/14 vs. 6/14) (p < 0.05). CONCLUSION: KMC managed babies had better weight gain, earlier hospital discharge and, more impressively, higher exclusive breast-feeding rates. KMC is an excellent adjunct to the routine preterm care in a nursery. PMID- 11770235 TI - Epidemiology of undernutrition. AB - OBJECTIVE: The present study was undertaken to find out the magnitude of the problem of under nutrition among the children under 5 years of age and also to identify the important factors influencing the nutritional status of the children. METHODS: 30 cluster sampling technique had been applied in the study. A total of 600 children below five years of age were covered. Twenty under five children from each cluster were chosen for the study which was carried out during January to February '97. As per IAP criteria a total of 60.29% children were undernourished and 3.92% were severely undernourished. According to NCHS standard 46.57% & 6.86% children had weight below-2SD and -3SD respectively. RESULTS: A statistically significant relationship was found between the different age groups and nutritional status of under 5 children. Severe degree of malnutrition had highest prevalence under two years of age. The influence of variables like age, sex, religion, literacy status of parents and morbidity of the children were significantly associated with malnutrition. CONCLUSION: Practice of exclusive breast feeding, introduction of timely complementary feeding, education for maintaining personal hygiene, proper implementation of UIP immunization, periodic deworming, standard case management of diarrhoea and ARI as well as continuation of feeding during illness may reduce malnutrition of under-five children. PMID- 11770236 TI - Rehabilitation of P.E.M. children. AB - OBJECTIVE: The High Density Diet (HDD) tested in this study is a diet prepared with indigenous food items and is therefore inexpensive. METHODS: Malnourished patients were inducted in three groups. Group A was given only high density diet (HDD) for 7 days and then given routine diet plus HDD for the next 7 days. Group B was given routine diet plus HDD for 14 days. Group C was given only routine diet for 14 days and was the control group. RESULTS: The results were best when HDD was used as a supplement to routine diet (group B). The average weight gain in gm/kg/day for this group was 6, while that for the control group was 2.1. Group A had a weight gain of 4.8 gm/kg/day. Similarly the average caloric intake for the controls was very low throughout the 2-week period, while group B had the best intake, which rose steadily from day one and reached 1200 calories on day 14. Children in group A had a maximum intake of 800 calories in the first week and in the second week this rose up to 1200, equaling that of group B. No case of vomiting, abdominal pain and cramps were reported. CONCLUSION: The High Density Diet is hence, low in cost, easy to prepare at home by mothers and effective in bringing about rapid weight gain in malnourished children. PMID- 11770237 TI - Maternal knowledge, attitude and practices towards diarrhea and oral rehydration therapy in rural Maharashtra. AB - OBJECTIVE: A cross sectional hospital based survey was undertaken in rural area of Wardha District of Maharashtra, to assess the knowledge, attitude and practices of mothers regarding diarrhea and oral rehydration therapy. METHODS: 75 mothers of under-five children participated [corrected] in the study. They were interviewed by an interviewer using a pre-designed and pre-tested questionnaire. RESULTS: 69.3% of them had a per-capita income of less than rupees 500 [corrected]. 68% of mothers knew the correct definition of diarrhea but only 5.3% of them were aware that diarrhea leads to dehydration [corrected]. 90.7% of mothers were aware of ORT and ORS was easily available to the majority, but only 60% of mothers [corrected] practiced ORT. Nearly 1/3rd of mothers were mixing ORS in the wrong fluid. Nearly half of the mothers were not practicing adequate hand washing, 32% were using feeding bottles [corrected]. CONCLUSION: The maternal knowledge towards diarrhea and ORS was inadequate in the population studied [corrected] and there was a big gap between actual and desired practices. PMID- 11770239 TI - Nested polymerase chain reaction in the diagnosis of congenital cytomegalovirus infection. AB - OBJECTIVE: Human cytomegalovirus infection is highly prevalent in Indian population. It is the commonest congenitally acquired infection causing various anomalies. The diagnosis of infection in neonates is difficult as IgM may not be detected in all cases. The polymerase chain reaction is reported as alternative and better option in these patients. However, there is lack of data to substantiate this preference in a resource poor country like India. METHODS: Blood samples from 930 neonates/fetuses were first tested for specific anti-CMV IgM antibodies using mu-capture enzyme linked immunosorbent assay, Mac-ELISA. Nested PCR was first standardised on clinically and therapeutically confirmed cases of CMV disease. In the second phase blood samples randomly from 20 babies suspected of CMV infection were collected for serology and PCR and both tests were run independently. Twenty healthy controls were also included. IgM ELISA and PCR were performed on these samples and results of these 20 samples were compared to evaluate the sensitivity and specificity of each method. RESULTS: Out of 930 serum samples of suspected congenital CMV infection 188 (20.2%) were found positive for CMV specific IgM antibodies. While comparing the results of 40 paired samples, PCR was found to be highly specific (100%) but less sensitive than Mac-ELISA (95%) with negative predictive value of 100% and positive predictive value of 95%. Thus in congenital CMV infection Mac-ELISA was less costly, less cumbersome and more user friendly. CONCLUSION: The Mac-ELISA seem to have parallel sensitivity and specificity as PCR for diagnosing congenital CMV infection. PMID- 11770238 TI - Betamethasone in plus phenobarbitone prior to hepatobiliary scintigraphy increases diagnostic accuracy in infants with jaundice. AB - OBJECTIVE: In the diagnostic work up of the child with neonatal obstructive cholangiopathy (NOC), hepatobiliary scintigraphy (HBS) determines the need for peroperative cholangiography (POC). Traditionally, phenobarbitone is recommended to prime the liver to HBS. This retrospective study was designed to evaluate whether addition of the betamethasone (BM) alters the diagnostic accuracy of the HBS in distinguishing neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA). METHODS: Between 1993-1999, 202 patients presented with NOC and this study was not designed as a prospective randomized clinical trial. Of these, 126 patients had received Phenobarbitone (Group I) and the remaining 76 (Group II) had received BM in addition to the PB in a dose of 5 mg/k/d and 2.2 mg/k/d respectively for 7 days prior to HBS. RESULTS: Retrospective analysis revealed that, in the Group I, 41 showed excretion and 85 did not show any excretion of the radiopharmaceutical and the latter underwent POC which revealed that 31 patients (36%) of them showed patent biliary tract. In group II, 32 patients revealed excretion and 44 did not show any excretion of the radiopharmaceutical and the latter had undergone POC, which revealed that only 8 patients (18%) showed patent biliary tract. The percentages of false positives (36% vs 18%) was statistically significant (p < 0.03). CONCLUSION: Addition of BM increases the diagnostic accuracy of the HBS and this would lead to decreased need for POC to distinguish NH from EHBA. PMID- 11770240 TI - National Family Health Survey and children. AB - This article aims to describe the National Family Health Survey (NFHS) being carried out in India with its first round during 1992-93 (NFHS-I) and second round during 1998-99 (NFHS-II), with special reference to information available in relation to children. The survey was on lines of the existing systems of Demographic Surveys (DHS) in various developed as well as developing countries. Another important objective of the survey was to provide quality data to the researchers to carry out analytical work on various aspects. Further, the survey has paved the way to carry out comparative studies not only between states in India but also between countries. An attempt has also been made here to present salient features of comparative results under NFHS-I and NFHS-II. PMID- 11770241 TI - Management of dengue fever in ICU. AB - Dengue virus infection can cause a wide spectrum of illness. Thrombocytopenia with concurrent haemoconcentration differentiates dengue haemorrhagic fever from classical dengue fever. Only cases with shock or unstable vitals signs need admission in the pediatric intensive care. The management is essentially supportive and symptomatic. The key to success is frequent monitoring and changing strategies. A rise in hematocrit of 20% along with a continuing drop in platelet count is an important indicator for the onset of shock. Patients in grade I and II should be closely monitored for signs of shock. The management of dengue shock syndrome (grade III and IV) is a medical emergency needing prompt and adequate fluid replacement for the rapid and massive plasma losses through increased capillary permeability. Early and effective replacement of plasma losses with plasma expanders or fluid and electrolyte solutions results in a favourable outcome in most cases. The ideal fluid management should include both cystalloids and colloids (including albumin). Cystalloids are given as boluses as rapidly as possible, and as many as 2 to 3 boluses may be needed in profound shock. Colloidal fluids are indicated in patients with massive plasma leakage and in whom a large volume of cystalloids has been given. Frequent recording of vital signs and determinations of haematocrit are important in evaluating the results of treatment. Apart from correction of electrolyte and metabolic disturbances, oxygen is mandatory in all patients of shock. Some patients develop DIC and need supportive therapy with blood products (blood, FFP and platelet transfusions). Polyserositis, in the form of pleural effusion and ascitis, are common in cases of dengue shock syndrome, and if possible, drainage should be avoided as it can lead to severe hemorrhages and sudden circulatory collapse. The prognosis depends mainly on the early recognition and treatment of shock. PMID- 11770242 TI - ICU management of severe malaria. AB - Malaria is very common in India. First step in management of malaria is to establish the diagnosis. It is established by using traditional smear or method like dipstick antigen captures assay which is simpler, accurate and doesn't require expertise. Next step is to look for signs and symptoms, which help cases of severe malaria should be admitted in intensive care unit (ICU) and antimalarial chemotherapy should be started through parenteral route. Complications like coma, anemia, renal failure, pulmonary edema, disseminated intravascular coagulation are not very uncommon. These complications should be anticipated and treated in time. There is no role of corticosteroids, mannitol in the treatment of cerebral edema. Therapeutic monitoring of severe malaria should involve quantitative estimation of parasite load. PMID- 11770243 TI - Nosocomial infections in pediatric intensive care units. AB - Nosocomial infections are a significant problem in pediatric intensive care units. While Indian estimates are not available, western PICUs report incidence of 6-8%. The common nosocomial infections in PICU are bloodstream infections (20 30% of all infections), lower respiratory tract infections (20-35%), and urinary tract infections (15-20%); there may be some differences in their incidence in different PICUs. The risk of nosocomial infections depends on the host characteristics, the number of interventions, invasive procedures, asepsis of techniques, the duration of stay in the PICU and inappropriate use of antimicrobials. Most often the child had endogenous flora, which may be altered because of hospitalization, are responsible for the infections. The common pathogens involved are Staphylococcus aureus, coagulase negative staphylococci, E. coli Pseudomonas aeruginosa, Klebsiella, enterococci, and candida. Nosocomial pneumonias predominantly occur in mechanically ventilated children. There is no consensus on the optimal approach for their diagnosis. Bloodstream infections are usually attributable to the use of central venous lines; use of TPN and use of femoral site for insertion increase the risk. Urinary tract infections occur mostly after catheterization and can lead to secondary bacteremia. The diagnostic criteria have been discussed in the review. With proper preventive strategies, the nosocomial infection rates can be reduced by up to 50%; handwashing, judicious use of interventions, and proper asepsis during procedures remain the most important practices. PMID- 11770244 TI - Fetal intracranial hemorrhage due to antenatal low dose aspirin intake. AB - Antenatal intake of low dose aspirin is advised for prevention of pregnancy induced hypertension, intrauterine growth retardation and pre-term labour. Aspirin has an anticoagulant effect due to its action on Cyclo-oxygenase and vitamin K dependent coagulation factors. It can readily cross the placental barrier and be a potential cause for bleeding tendency in the fetus. Fetal intracranial hemorrhage, following low dose aspirin administration in a mother and subsequent effect after delivery is being reported. PMID- 11770245 TI - Neurocysticercosis presenting as psychiatric illness. AB - Neurocysticercosis is a common neuroparasitosis. Presentation with psychiatric symptoms is uncommon in neurocysticercosis. The present paper describes a patient who presented with mutism, neglect of personal care and incontinence in a psychiatric setting and investigations revealed diagnosis of neurocysticercosis. The case report highlights the possible misdiagnoses of a case of neurocysticercosis as psychiatric illness and mutism as an uncommon presentation of neurocysticercosis. PMID- 11770246 TI - Pancreatoblastoma. AB - Pancreatoblastoma is an extremely rare pancreatic tumor in childhood, comprising 0.5% of pancreatic non endocrine tumors. Just over 50 cases have been reported in the literature till 1997. A 10 year-old male child presented with mass abdomen of 9 months duration. USG and CT abdomen showed a large mixed density lobulated mass in abdomen anterior to, and displacing down the portal vein and splenic veins. Exploratory laparotomy revealed a large mass, arising from body and tail of pancreas, not infiltrating the adjacent structures. Complete excision of the mass along with removal of body and tail of pancreas was done. The histopathological examination revealed pancreatoblastoma. He is well without any evidence of disease 6 months after the operation. To the best of our knowledge this is the first case of pancreatoblastoma with a large size (25 x 20 x 15 cm,) weight 2.5 kg, which was localized and where complete excision was possible. The largest size reported in the literature reviews has been around 15 cm. The literature review confirms that an aggressive surgical attack on resectable pancreatoblastoma may often be curative. The role of adjuvant chemotherapy or radiotherapy is still under discussion due to small number of patients treated as yet. PMID- 11770247 TI - Neonatal Salmonella typhimurium meningitis. AB - Meningitis due to Salmonella is a very rare sign of Salmonellosis. A 10-day-old female premature neonate with Salmonella typhimurium meningitis is presented in this report. The clinical features, outcome and antibiotic treatment are discussed. Although it is extremely rare, Salmonella meningitis should be considered in differential diagnosis of neonatal meningitis. PMID- 11770248 TI - Cerebral thrombosis in beta-thalassaemia major. AB - Two patients with homozygous beta thalassaemia complicated by cerebral thrombosis are reported. An alteration in coagulability due to a sudden increase in haematocrit and platelets was the probable cause in one patient. Although the other patient had many complications of thalassaemia, the cause for cerebral thrombosis was not identifiable. PMID- 11770249 TI - Adhalin deficiency: an unusual cause of muscular dystrophy. AB - Childhood muscular dystrophies have a wide clinical spectrum, motor disability and are variably inherited. Although the phenotype may appear similar they may represent distinct genetic entities. Advances in immunohistochemistry, gene deletion and linkage studies have enabled precise characterization. We report a family with an early onset weakness and calf pseudo hypertrophy in 2 male sibs with an usually mild course. Deletion screening was negative for 24 exons of the DMD gene in both. Muscle immunohistochemistry revealed normal dystrophin I and II staining but complete absence for adhalin, a dystrophin associated glycoprotein. Classifying them as adhalinopathy. Severe childhood autosomal recessive muscular dystrophies (SCARMD) result from mutation in the sarcoglycan complex (59). Adhalinopathy is now used to describe SCARMD. The adhalinopathy described in our patients is the first report from India. PMID- 11770250 TI - Antenatal diagnosis of choledochal cyst. PMID- 11770251 TI - An unusual serotype of Salmonella from a case of meningitis in a neonate. PMID- 11770253 TI - [Hospitalizations in a cohort of 175 severely drug-addicted patients of a medically managed opiate withdrawal project]. AB - In this study we investigated a population of 175 seriously drug addicted patients. They were randomised in a controlled opiate maintenance program in Basel, Switzerland. We investigated hospitalizations in the time period three years before entry into the program and approximately 3.5 years after entry into this program. The mean age was 28.4 years, the mean drug injection time was 8.8 years. 82.6% of the patients were seropositive for HCV and 21.5% were HIV infected. We observed 223 hospitalizations in 100/175 patients during the observation period of 6.5 years. Most commonly infections (n = 94), different diseases of internal medicine (n = 44) and surgical diseases (n = 41) led to hospitalization. Altogether, we found no decrease of the incidence of hospitalisations. However, there was a significant decrease of directly drug induced diseases (p < 0.05). So far, hospitalizations did not diminish in this well-controlled opiate maintenance program. However, as shown in earlier studies, the incidence of HIV drastically dropped. Hence, it may be that a longer follow up may prove beneficial regarding the incidence of hospitalisations. PMID- 11770252 TI - [Photographic documentation of the effectiveness of 1 mg. oral finasteride in treatment of androgenic alopecia in the man in routine general practice in Switzerland]. AB - A 6-month, prospective, open, multicenter cohort study in 265 men with male pattern hair loss treated with oral finasteride 1 mg/day (Propecia) was conducted in the office of 52 Swiss dermatologists. The patient's head was placed in a stereotactic device, and Polaroid photographs were taken of the vertex and frontal areas. Endpoints used to determine treatment efficacy were patient self assessment, investigator clinical assessment, and blinded assessment of the serial Polaroid photographs by a panel of 2 experienced dermatologists. Significant improvements were stated on the photographs by both clinical investigators and the blinded expert panel: 54% of patients showed improvement of hair growth at 6 months of treatment in the vertex region, and 48.7% in the frontal area. No progression of hair loss was found in an additional 38% (vertex) and 47% (frontal region), respectively. Clinical investigator and expert assessment yielded comparable results. Independently, patient self-assessment and investigator clinical assessment confirmed the progress. Propecia was well tolerated, and no significant safety concerns were identified during the study. The photographic method was well accepted by the physicians. The office-based Polaroid photographic system allowed reliable assessment of change during treatment of male pattern hair loss with Propecia. The data generated in this manner corresponded to the antecedent results of the multicenter, placebo controlled studies with oral finasteride. PMID- 11770254 TI - [Adrenal insufficiency caused by treatment with levothyroxine]. AB - Primary adrenal insufficiency is a rare disease. Its diagnosis remains a clinical challenge since the signs and symptoms of the disease are insidious in onset and non specific in nature. A case report of Addison's crisis induced by levothyroxine substitution therapy is described. This clinical case is discussed in details with a special emphasis to the published literature regarding the strategy of diagnosis and the specific therapy of primary adrenal insufficiency. PMID- 11770255 TI - [Nuclear medicine diagnosis of kidney function in unilateral urinary tract dilatation in childhood]. AB - Ultrasound accurately detects hydronephrosis in infants and children, while nuclear medicine techniques quantify relative renal function in addition to characterize the urodynamic relevance of hydronephrosis. Because ultrasound fails to estimate the potential reduction of relative kidney function with more severe hydronephrosis and moreover, renal function is not necessarily affected by hydronephrosis, renal scintigraphy is indicated to assess the functional status of hydronephrotic kidneys for both, split renal function and postrenal urine drainage without and, if necessary, with furosemide intervention. PMID- 11770256 TI - [32-year-old patient with recurrent infections of the respiratory tract, general fatigue and decreased IgA, IgG and IgM]. PMID- 11770257 TI - The reactions of methanimine and cyanogen with carbon monoxide in prebiotic molecular evolution on earth. AB - A primeval atmosphere is proposed containing simple molecules such as formaldehyde, ammonia, carbon monoxide, cyanogen and hydrogen cyanide, which have been detected in space. Chemical reactions are described for the formation of aziridine-2-one and di-azirine-3-one derivatives as potential precursors for the original synthesis of amino-acids, proteins, pyrimidines, purines, nicotinamide and flavin. The reactions have been shown to be kinetically feasible from the overall enthalpy changes in the ZKE approximation at the MP2/6-31G* level. PMID- 11770258 TI - Enantiomeric crystallization from DL-aspartic and DL-glutamic acids: implications for biomolecular chirality in the origin of life. AB - Amino acids in living systems consist almost exclusively of the L-enantiomer. How and when this homochiral characteristic of life came to be has been a matter of intense investigation for many years. Among the hypotheses proposed to explain the appearance of chiral homogeneity, the spontaneous resolution of conglomerates seems one of the most plausible. Racemic solids may crystallize from solution either as racemic compounds (both enantiomeric molecules in the same crystal), or less commonly as conglomerates (each enantiomer molecule separate in different enantiomeric crystals). Only conglomerates can develop a spontaneous resolution (one of the enantiomeric molecule crystallizes preferentially, the other one remains in solution). Most of natural amino acids are racemic compounds at moderate temperatures. How can we expect a hypothetical spontaneous resolution of these amino acids if they are not conglomerates? In this paper we show how DL aspartic and DL-glutamic amino acids (racemic compounds), crystallize at ambient conditions as true conglomerates. The experimental conditions here described, that allows this 'anomalous' behaviour, could be also found in natural sedimentary environments. We suggest that these experimental procedures and its natural equivalents, have a potential interest for the investigation of the spontaneous resolution of racemic compounds comprising molecules associated with the origin of life. PMID- 11770259 TI - Ala-His mediated peptide bond formation revisited. AB - The historical origin of the translation machinery remains unresolved. Although the large 23S ribosomal RNA (rRNA) is almost certainly the catalytic component of the peptidyl transferase center in the modern ribosome, it is likely that greatly simplified systems were initially employed in the late stages of the prebiotic world. In particular, it has been suggested that small RNAs carrying amino acids were important for the genesis of protein synthesis. Consistent with this, a dipeptide, Ala-His, was previously claimed to be a prebiotically feasible catalyst mediating peptide bond formation in the presence of aminoacylated tRNA and cognate mRNA template, in the absence of other ribosomal components (Shimizu, 1996). We herein report a detailed study of putative dipeptide formation by Ala His and RNAs carrying leucine. Based on the results presented here, it is unlikely that the dipeptide, Ala-His, catalyzes significant levels of Leu-Leu dipeptide formation in solution. A product is produced which can be readily mistaken for a dipeptide in the TLC separation systems employed in earlier work. We offer explanations for the formation of this product as well as another unexpected product. The results presented here are consistent with the notion that the translation machinery was likely based on catalytic RNA from its very inception. PMID- 11770260 TI - Protection of bacterial spores in space, a contribution to the discussion on Panspermia. AB - Spores of Bacillus subtilis were exposed to space in the BIOPAN facility of the European Space Agency onboard of the Russian Earth-orbiting FOTON satellite. The spores were exposed either in dry layers without any protecting agent, or mixed with clay, red sandstone, Martian analogue soil or meteorite powder, in dry layers as well as in so-called 'artificial meteorites', i.e. cubes filled with clay and spores in naturally occurring concentrations. After about 2 weeks in space, their survival was tested from the number of colony formers. Unprotected spores in layers open to space or behind a quartz window were completely or nearly completely inactivated (survival rates in most cases < or = 10(-6)). The same low survival was obtained behind a thin layer of clay acting as an optical filter. The survival rate was increased by 5 orders of magnitude and more, if the spores in the dry layer were directly mixed with powder of clay, rock or meteorites, and up to 100% survival was reached in soil mixtures with spores comparable to the natural soil to spore ratio. These data confirm the deleterious effects of extraterrestrial solar UV radiation. Thin layers of clay, rock or meteorite are only successful in UV-shielding, if they are in direct contact with the spores. The data suggest that in a scenario of interplanetary transfer of life, small rock ejecta of a few cm in diameter could be sufficiently large to protect bacterial spores against the intense insolation; however, micron-sized grains, as originally requested by Panspermia, may not provide sufficient protection for spores to survive. The data are also pertinent to search for life on Mars and planetary protection considerations for future missions to Mars. PMID- 11770261 TI - [Family with malaria: from the asymptomatic to life-threatening]. AB - Five members of a Dutch family of Nigerian origin (three girls aged 1, 6 and 8 years and their parents, mother aged 32 and father aged 41 years), had been infected with Plasmodium falciparum during a visit to Nigeria. The mildest infection could be treated at home with oral medication. The severest case had to be admitted to the paediatric intensive care unit for respiratory support and exchange transfusions. Four patients were treated with quinine. A combination of atovaquone and proguanil was added, resulting in a quick decline of the parasitaemia. Whenever a patient is suspected of malaria, laboratory tests should be carried out immediately and treatment should be started as soon as possible, in order to prevent possible complications. The early recognition of any of the alarm symptoms, for example, lowered consciousness, abnormal respiratory movements, cold extremities, convulsions, hypoglycaemia, severe anaemia and a high parasitaemia, whether at casualty or the general practitioner's surgery is crucial. PMID- 11770262 TI - [Infectious diseases as a weapon: vigilance is needed]. AB - The deliberate inclusion of Bacillus anthracis spores in mail has led to several cases of anthrax in the USA of which to date four have been fatal. Shortly before these incidents, the Health Council of the Netherlands had issued an advisory document which stressed the need for a well-established infrastructure and rigorous protocols so that an immediate and adequate response to cases of bioterrorism could be ensured. Physicians are expected to know the characteristics of the relevant diseases and to immediately notify the Health Inspectorate in the event of an infectious cluster which is unusual with respect to time, place or age, a cluster of a highly serious disease in healthy persons, or a cluster characterised by flaccid paralysis with bulbar signs. PMID- 11770263 TI - [Anthrax due to deliberate infection]. AB - Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and intestinal form. The pulmonary form can be rapidly fatal but is difficult to recognise due to an initially non-specific, flu-like clinical picture. As a result of spores being inhaled, a mediastinal lymphadenitis arises from which a systemic disease develops with a violent toxaemia, damage to the vascular endothelium, oedema, internal haemorrhages and circulatory collapse. Anthrax is diagnosed by demonstrating the presence of the bacteria in the cutaneous abnormality, in blood or another sterile body component such as cerebrospinal fluid, by means of a direct preparation, immunofluorescence or surface antigens, molecular diagnostics with PCR, or by means of culturing. B. anthracis is sensitive to quinolones, clindamycin and tetracyclines, and often to penicillin. Although naturally acquired cutaneous anthrax can be effectively treated with a short antibiotic cure, it is nevertheless advised in the USA to complete the full 60-day cure and to regard the cutaneous manifestation as a telltale sign of possible respiratory exposure. Anthrax is not transmitted from one person to another. PMID- 11770264 TI - [Myotoxicity and rhabdomyolisis due to statins]. AB - Rhabdomyolysis is a rare but potentially fatal complication associated with the use of cholesterol synthesis inhibitors (statins). The complication can develop in susceptible patients and with the concomitant use of medications that impede the biodegradation of statins, for example, biotransformation via the cytochrome P450 system. This may result in the plasma and tissue concentrations of statins, and their active metabolites, increasing to levels that are toxic for striated muscle. Myopathy is present when plasma activity levels of creatinine kinase are raised to in excess of 10 times the upper limit of the normal value. Muscular complaints which may be indicative of myotoxicity and subsequent myopathy are present in 1-7% of statin users. Albeit to varying degrees, all statins can induce myotoxicity especially at high dosages. Rhabdomyolysis was clearly more prevalent under cerivastatin users than the users of other statins and was therefore recently withdrawn from the market. Statins should be withdrawn immediately if myopathy is suspected. Prompt withdrawal may prevent rhabdomyolysis. PMID- 11770265 TI - [Clinical thinking and decision making in practice. A patient with postpartum malaise, anorexia, and ventricular tachycardia]. AB - A 34-year-old woman was hospitalised with hypotension, lethargy and ventricular tachycardia, five months after an uneventful pregnancy and delivery. Laboratory values were compatible with anterior (abnormal concentrations of adrenocorticotropin hormone, thyroid stimulating hormone, prolactin) and posterior (diabetes insipidus) pituitary gland insufficiency. An MRI scan revealed that there was no pituitary enlargement and that the pituitary stalk was normal. The prompt recognition of hypophysitis as a potentially fatal condition is important, as a life-saving treatment is available. PMID- 11770266 TI - [Diagnostic image (67). Fibrous dysplasia of the thorax wall]. AB - In a 55-year-old woman extensive fibrous dysplasia of the ribs with destruction of the thorax was discovered, for which she was successfully treated surgically. PMID- 11770267 TI - [Female patient with cutaneous anthrax in Belgium]. AB - A 23-year-old Turkish woman was admitted with an infection of the left thumb. The clinical picture was typical for cutaneous anthrax. Microbiological tests confirmed the diagnosis 'infection by Bacillus anthracis'. She recovered when treated with penicillin, although later tests revealed that the bacteria were resistant to this antibiotic. The patient became infected in Belgium as a result of wounding herself on the teeth of an illegally slaughtered sheep, which had possibly become infected in the pasture. Recognising the characteristic clinical picture of cutaneous anthrax is essential for prompt treatment and a favourable prognosis. PMID- 11770268 TI - [Rupture of thoracic aneurysm in a 10-year old boy]. AB - A 10-year-old boy with a medical history of fatigue became nauseous, short of breath and cyanotic within 24 hours after a frightening incident. He was successfully resuscitated after a cardiac arrest. A CT scan revealed a ruptured aneurysm of the ascending aorta. During emergency surgery the ascending aorta and aortic arch were replaced with a 22 mm synthetic graft. No postoperative complications occurred. There was no associated trauma, syphilis, collagen diseases (Marfan's syndrome, Ehlers-Danlos syndrome), congenital heart disease or autoimmune disease. The cause of the aneurysm and rupture remain unclear. PMID- 11770270 TI - [Dutch Burial Act]. PMID- 11770269 TI - [Esophageal rupture with aortic-esophageal fistula due to ingestion of foil packaged drugs]. PMID- 11770271 TI - [Is there progress to be made in contraception?]. PMID- 11770272 TI - [(18F)-fluoro-2-deoxyglucose PET in imaging of gynecologic cancers]. AB - Although gynaecological cancers are not currently part of the clinical indications in the French registration for [18F]-fluoro-2-deoxyglucose (FDG), various studies indicate in this context a potential clinical benefit of imaging with this radiopharmaceutical and PET, a new imaging modality that can be performed either with a dedicated machine or with a "hybrid" gamma-camera (CDET). The potential indications of FDG-PET in mammary, ovarian or cervical cancers are reviewed according to the diagnostic phase: screening, tumour characterisation, staging, therapeutic follow-up and search for recurrence. By pooling the published results, the accuracy of FDG-PET could be estimated with a reasonable precision in various clinical settings: characterisation of a breast tumour (598/696 = 86%), lymph node invasion in breast cancer (525/602 = 87%), recurrence of breast cancer (114/127 = 90%), characterisation of adnexal masses (130/176 = 78%), recurrence of ovarian cancer (152/172 = 88%), lymph node invasion in cervical cancer (98/103 = 95%). Authors also present original data concerning their experience of recurrence detection with CDET in breast or ovarian cancers. In 44 patients suspicious of recurrence of breast cancer, FDG-CDET sensitivity was 94%, specificity 82% and accuracy 91%; in 18 patients suspicious of recurrence of ovarian cancer, specificity, sensitivity and accuracy were 100%. The impact of dedicated PET and CDET examinations performed by our team during year 2000, led, according to 63 forms returned to us, to a modification of stage in 48% of breast cancers, 36% of ovarian cancers, 43% of cervical cancers and above all induced a modification in patients' management in respectively 69%, 64% and 60% of cases, more than the average rate in cancer patients which was 50%. No significant difference was observed between clinical impact of dedicated PET and CDET examinations. PMID- 11770274 TI - [Value of fetal fibronectin research for predicting premature delivery]. AB - OBJECTIVE: To estimate the performance of the foetal fibronectin test as a predictor of preterm delivery. PATIENTS AND METHODS: This prospective study concern 61 patients who had a singleton pregnancy between 24 and 36 weeks of gestation and were hospitalized because of a threatened preterm labor without premature rupture of the membranes. For each patient the presence of foetal fibronectin in cervicovaginal secretions was determined with a rapid swab-test. RESULTS: Prematurity rate was 38% (23 patients). In case of positive result, delivery became before 37 weeks in 75% (12/16) against 24% in case of negative result (11/45). The prolongation of pregnancy after the test was on average 21 days in the positive group and 44 days in the negative group. About the prediction of preterm delivery, the results showed a sensibility of 52%, a specificity of 89%, a positive predictive value of 75%, a negative predictive value of 76%. To predict a delivery within the two weeks after the test, the sensibility was 88%, the specificity 83%, and the negative predictive value 98%. CONCLUSION: The presence of foetal fibronectin in cervicovaginal secretions represent an increased risk of preterm delivery, whereas its excellent negative predictive value allow to be reassuring, especially within a period of 15 days. PMID- 11770273 TI - [Liquid phase cytology in the primary screening for cervical cancer: a multicenter study]. AB - The aim of this six-centre, split-sample study was to compare ThinPrep fluid based cytology to the conventional Papanicolaou smear. Six Cytopathology laboratories and 35 Gynaecologists participated. 5428 patients met the inclusion criteria. Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded. On initial screening, 29% more ASCUS and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (p = 0.001). Independent and consensus review confirmed 145 LSIL + diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (p = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap Test and has the potential to optimize the effectiveness of primary cervical cancer screening. PMID- 11770275 TI - [Evaluation of weight and morphotype of French women in gynecological consultation]. AB - Weight and morphology change with age in proportions which depend on numerous environmental factors. This French study on 3,000 women age between 40 and 70, seeing their gynecologist, has shown that the average body mass index of this population is 23.97 kg/m2, and that the waist hip ratio is 0.81. Those two parameters increase with age and are reduced when women have a physical activity for more than 2 hours a week and are on oral contraception or hormone replacement therapy. Women on percutaneous hormone replacement therapy have a lower body mass index and a lower waist hip ratio. Cigarette smoking goes with a lower body mass index. When it dates back to more than 5 years, menopause is associated with a body mass index increase. In this population, the proportion of women under hormone replacement therapy is 69%, mostly percutaneous estrogenotherapy on a discontinuous sequential rhythm. PMID- 11770277 TI - [Ritualistic female genital mutilation. The sentiment of the women]. AB - Female genital mutilation (FGM) is considered as the most dangerous custom still ritually practiced and 2 million girls undergo the ordeal each year. This practice is anchored and fixed firmly in numerous African people's culture and Western countries are confronted to it through African immigrants. In order to understand the justifications and the consequences of FGM we interviewed 14 genitally mutilated African women living in France. Unfortunately and despite the conscious knowledge of consequences and absurd side of such practice, yet it seems to be perpetuated over the descendants. Educational approach is the best solution to fight female genital mutilation fixed firmly in numerous African people's culture. PMID- 11770276 TI - [Torsion of the accessory spleen: an atypical etiology for acute abdomen]. AB - The accessory spleen is often a incidental discovery. The accessory post accidental spleen are unusual. The torsion of a movable spleen is possible and represent about 0.2 to 0.3% of splenectomy. But the torsion of an accessory spleen is exceptional. A case of acute torsion of an accessory spleen is reported. In a 26-year-old women was admitted with acute abdominal pain. The abdominal ultrasound and the abdominal X-Ray are no specific. In the face of the acute pain, a laparoscopy was necessary. At laparoscopy, the patient was found to have torsion and infarction of an accessory spleen in the pelvis. The treatment was a splenectomy and the evolution was favorable. PMID- 11770278 TI - [Septate uterus and reproduction disorders: current results of hysteroscopic septoplasty]. AB - Uterus septus is the most frequent congenital uterine anomalies caused by insufficient resorption of the mullerian ducts. Retrospective statistical analysis shows that the uterine septa have the worst reproductive outcome with a high incidence of early abortions. It is well recognized that it increased the incidence of recurrent (> or = 3) miscarriages (79% among 1,601 pregnancies), reproductive failure and obstetric complications. A septate uterus does not seem to be an infertility factor. On the other hand, the incidence of unexplained infertility was significantly higher (40%) in the patients with secondary infertility; thus, a contribution from the uterine septum in delayed conception of these patients cannot be excluded. Hysteroscopic surgery has replaced conventional abdominal route. Hysteroscopic metroplasty improves obstetrical prognosis in women with septate uterus, and it's advantages are easiness, low morbidity rate, without the hysterotomy's consequences like adnexial adhesions. Metroplasty is indicated in women with a history of miscarriages (2 or more), which decreased to 15%, in patients with an unexplained infertility, and in women in whom assisted reproductive treatment is being contemplated. Combined with laparoscopy, the hysteroscopic metroplasty is the gold standard for assessing uterine septa, especially in these infertile women. Laparoscopy also is required to complete the diagnostic work up of infertility, and provides an opportunity to treat any coexisting pelvic pathology. PMID- 11770279 TI - [The biological distribution of thrombosis in the year 2000]. AB - Acquired or genetic risk factors for thrombosis are present in about fifty per cent of the patients with venous thromboembolic disease. In order to evaluate the contribution of genetic defects in the pathogenesis of thrombosis, the laboratory investigation will include search for the factor V Leiden and prothrombin Leiden mutations, and for antithrombin, protein C and protein S hereditary deficiencies. Search for antiphospholipid antibodies and factor VIII plasma levels measurements will be also performed. PMID- 11770280 TI - [Alternatives to hormonal treatment for the prevention of postmenopausal osteoporosis: the bisphosphonates]. PMID- 11770281 TI - [Standards, options and recommendations for the management and initial care of patients with malignant epithelial ovarian tumors (abridged version)]. PMID- 11770282 TI - Eleven-color flow cytometry. A powerful tool for elucidation of the complex immune system. AB - This article describes application of some of the most sophisticated flow technology currently available. Both basic and clinical research applications of this technology are illustrated, showing how a new picture of immune function arises that can simplify the understanding of immunopathogenesis of disease. Although the implementation of this technology in the clinic is still several years off, it can serve to identify important correlates of immune function that can be measured with today's technology. PMID- 11770283 TI - Overview and application of suspension array technology. AB - A cell-based solid-phase immunoassay usually is called immunophenotyping when performed on a flow cytometer. Using the same principles, there is a new flow cytometric application available with the suspension array technology. The significant difference is that the immunologic reaction does not occur on the surface of leukocytes, but rather on the surface of plastic fluorospheres. This is a multiplexed solid-phase flow cytometry-based technology with some clinically relevant potential. PMID- 11770284 TI - Microsphere-based molecular cytometry. AB - Flow cytometry has recently gained attention as a powerful high-throughput technology for the analysis of molecular interactions. This recognition is mostly because of the development and use of fluorescently distinct microsphere populations. Recent applications of this technology have included detecting analytes, monitoring enzymatic activity, and genotyping SNP. This article expands the list of applications by highlighting nuclear receptor-coactivator peptide binding studies. Nuclear receptors initiate gene transcription by binding to a wide variety of accessory factors. Small molecule ligand binding by nuclear receptors modulates the interaction with some of these cofactors. Because a typical cell contains numerous cofactors, multiplexed analysis of nuclear receptor binding to coactivator peptide-coupled microspheres is a valuable approach to rapidly assess this network of complex interactions. Understanding how ligand binding regulates these interactions should help in the design of improved small molecule therapeutics. The latter part of this article has focused on the recent application of multiplexing protein:protein interactions. Developing protein interaction networks will be paramount as a greater understanding of the human genome is developed. In the future, flow cytometric analysis of fluorescent microspheres may be applied to any array of interacting molecules and may have broader applications in the area of proteomics. PMID- 11770285 TI - Quantitative flow cytometry. AB - Flow cytometers are instruments that can quantify fluorescence intensity data and provide unique information about cell populations. Significant advances have been made in terms of calibration reagents, evaluation of the quality and limitations of the monoclonal antibodies, standardized sample preparation, and data analysis to ensure interlaboratory comparability and reproducibility. Efforts to standardize quantitative fluorescence intensity measurements impact current clinical flow cytometry applications (i.e., immunophenotyping), but also emerging technologies, such as microarray assays, which also require calibration of fluorescence intensity across different platforms. PMID- 11770286 TI - Immunophenotypic analysis with enhanced sensitivity of detection by enzymatic amplification staining. AB - Single cell analysis by flow cytometry is a powerful diagnostic modality that has been limited by poor resolving power. Molecules expressed on the cell surface in abundance (i.e., greater than 1000 molecules per cell) can be detected readily by conventional staining technologies; however, molecules expressed in lower concentrations cannot be easily observed. Because there are many molecules that are functionally significant at lower levels of expression, the capability to detect these molecules is important. Enzymatic amplification staining is a new flow cytometric amplification technology based on the enzymatically catalyzed deposition of reporter molecules. This technology allows for the detection of molecules expressed on the cell surface at low abundance. The authors have demonstrated that EAS can be used to resolve the expression of molecules that cannot be resolved with standard amplification procedures. It has been shown that this capability is valuable in the diagnostic evaluation of patient samples; moreover, it is likely that EAS can be profitably used in the analysis of both malignant and reactive blood cells from various patients. PMID- 11770287 TI - Clinically relevant functional flow cytometry assays. AB - As a lymphocyte proceeds along the pathway of cell division from the very earliest events of receptor aggregation-kinase activation to the final physical process of cell division, several physiologic functions occur, which can be measured by flow cytometry. Many of the functions along this pathway can be induced and measured in vitro and have led to the development of clinically relevant tests, which have been reviewed as functional flow cytometry procedures. It must be noted, however, that in addition to all of the physiologic processes that occur in lymphocytes (and in fact most cells) along the pathway to proliferation there are also several differentiated immune functions that are subject to flow cytometric analysis. Procedures for the evaluation of immune functions, such as phagocytosis, cellular aggregation, natural killer-cell cytotoxicity, cytokine secretion, antibody secretion, and antigen-specific cellular cytotoxicity assays have all been described. PMID- 11770288 TI - Clinical cytokine network cytometry. AB - Cytokines play an important role in human health and disease. Monitoring their effects and detecting alterations in the complex balance of cytokines within a patient will undoubtedly become increasingly common in the clinical laboratory. Because of the complexity of the network interactions, multiple assays measuring soluble cytokines ("what"), cytokine-producing cells ("who"), surface receptors ("where"), and function (how) simultaneously are necessary to provide clinically useful information. The explosion of reagents and applications for use in the clinical flow cytometry laboratory makes this the perfect setting to perform the multidimensional studies required. Clinical cytokine network cytometry exemplifies the power of multiparameter, high throughput technologies that will change the face of clinical laboratories in the twenty-first century. PMID- 11770289 TI - Contributions of flow cytometry to the analysis of the myelodysplastic syndrome. AB - As the population of North America ages, the incidence of MDS is likely to rise. Epidemiologic survey instruments need to be put in place to document changes in the incidence. The basic mechanism of disease in MDS is largely unknown. No unifying, testable hypothesis is yet available, but apoptosis, with mitochondria playing a key role, are central to any discussion of MDS. Cytogenetic abnormalities have not provided an explanation of MDS but are of diagnostic and prognostic significance. The emergence of immunologic factors is of major importance and emphasizes the need for early detection. Flow cytometry can be used diagnostically to exclude other causes of cytopenias, document the phenotypic manifestations of myeloid dysmaturation, and provide blast enumeration. The distinctions between MDS and acute leukemia are arbitrary, and the process should be conceptualized as a continuum. There is a need for continued work to establish minimal diagnostic criteria for MDS. The current prognostic scoring systems do not incorporate findings from the newer technologies. PMID- 11770290 TI - Diagnostic utility of red cell flow cytometric analysis. AB - Although most of the diagnostic applications of flow cytometry bring forth examples of leukocyte immunophenotyping for immunodeficiency diseases and leukemia-lymphoma diagnosis, the same technology has improved medical assessment of diseases affecting the red cell and erythropoiesis. Flow cytometric methods were first applied to laboratory hematology with the improvement in reticulocyte counting and the creation of the immature reticulocyte fraction for better anemia evaluation and therapeutic monitoring. A more recent improvement attributable to flow cytometry is accurate detection of fetal red cells in the evaluation of FMH hemorrhage. The same method used in the detection of fetal RBCs based on HbF content measurement using monoclonal antibodies also offers the potential for enumeration of F cells, which promises to have use in therapeutic monitoring of patients with sickle cell disease and the evaluation of other hemoglobinopathies and myelodysplasia. Other clinical uses of flow cytometric RBC analysis include nonisotopic red cell survival studies, sensitive blood group typing, sensitive detection of immune-mediated hemolytic diseases, and evaluation of parasitic diseases whose life cycle involves intracellular RBC infestation. This article summarizes red cell flow cytometry, particularly as it impacts the areas of immunohematology and laboratory hematology, and points to areas of potential future contribution of this technology to diagnostic medicine. PMID- 11770291 TI - An update on the use of flow cytometry in HIV infection and AIDS. AB - Flow cytometry has played an invaluable role in recent advances made against HIV and AIDS, and there is every reason to expect it will continue to do so. Newer generation machines, using three- and four-color panels, make measurements of lymphocyte subsets ever more accurate and potentially cost-effective. Similarly, recent single-platform techniques promise even more efficiencies, freeing CD4 enumeration from parallel determination of the CBC. In other developments, quantitative reporting of immunophenotype may well change the way subsets traditionally defined by qualitative determinations are viewed. The most promising initial candidates for such changes are surrogates of immune activation, such as CD38 expression on CD8 cells. But technical demonstration of reproducibility and reliability, and clinical trial evidence of utility- especially as measured against such established laboratory parameters as CD4 cell and HIV RNA determinations--are needed before a change from qualitative to quantitative immunophenotype measurement can be widely accepted. Although too soon to tell if they will emerge from the research arena into the clinical arena, tetramer binding, intracellular cytokine detection, and assays of cell division are rapidly advancing understanding of HIV-disease, and indeed understanding of all of human immunology. Some of these assays provide often subtly different information, and together they will help determine the most important surrogate measures of clinical immunity. Identifying such surrogates is critical to developing a rational HIV vaccine. The power of flow cytometry is its ability simultaneously to analyze data in four, five, six, or more dimensions. For longitudinal experiments, time adds yet another dimension. Humans struggle to think past three dimensions; interpreting results from experimental permutations and combinations that expand geometrically with each additional parameter studied requires considerable effort. Ultimately computer programs might come to our aid, but for now we have to live with the information overload if we hope to gain insight into the workings of complex biologic systems. In a world of limited resources, and with limited capacity to conceptualize in multiple dimensions, insight, inspiration, and perhaps a little luck are needed to ask the right questions and use the right assays if the recent string of advances against AIDS is to continue. PMID- 11770292 TI - Use of flow and laser scanning cytometry to study mechanisms regulating cell cycle and controlling cell death. AB - Applications of FC and more recently LSC in the fields of cell cycle progression and cell death already have revealed a wealth of knowledge about mechanisms involved in regulation of these pathways. The cytometry instrumentation and the associated methodologies complement tools of molecular biology by providing information that is unavailable from the latter alone. The use of cytometry side by side with classic molecular biology methods offers the means for deeper exploration of these mechanisms at molecular and cellular levels. Recent years brought the availability of new cytometric probes that sense the functional changes in the cell, such as chemical modifications (phosphorylation, acetylation, ubiquitinylation, and so forth) of the regulatory molecules, or their translocations between different cell compartments. Such probes will be particularly useful in mechanistic studies on cell cycle and cell death. One expects that the progress in these fields will expand at a continuously accelerating pace, propelled by development of new methodologies and probes. One of the dominating motors for this progress will be further development of cytometry instrumentation and the applicability of this instrumentation, methods, and probes. PMID- 11770293 TI - DNA and cell cycle analysis as prognostic indicators in breast tumors revisited. AB - Both DNA ploidy and S-phase ploidy are promising prognostic factors for node negative breast cancer patients. Based largely on the analysis of one large study, much of the reported problems with these factors have been caused by some unappreciated complexities in categorizing DNA ploidy into low- and high-risk groups and the lack of some necessary adjustments to eliminate unwanted correlations between DNA S-phase and ploidy. When both DNA ploidy and S-phase are compensated properly, they become independent prognostic markers, forming a powerful prognostic model. PMID- 11770294 TI - Microbiology. AB - Although flow cytometry can detect microorganisms rapidly in low concentrations in some clinical samples, it has not proved cost-effective for clinical use in this application. Adaptation of fluorescence multiplexing methodology recently developed for flow cytometric bead immunoassays, and the introduction of hybrid cytometers based on microfluidic technology, however, may make it possible to place cost-effective cytometric apparatus in clinical microbiology laboratories in the near future. PMID- 11770295 TI - Conformal radiotherapy for brain tumors. AB - The technical improvements of three-dimensional conformal radiotherapy can decrease the toxicity of brain treatment to acceptable levels. The adoption of the technique by more centers would allow for the potential advantages of three dimensional radiotherapy to be employed in a greater number of patients. Further studies evaluating the use of three-dimensional conformal radiotherapy in patients with nervous system neoplasms should focus on determining the effects on quality of life for the patient and survival compared with more standard treatment techniques. PMID- 11770296 TI - Stereotactic radiosurgery for brain tumors. AB - In the 50 years since Leksell developed the concepts and initial hardware for modern brain radiosurgery, the treatment has progressed to the point where it is used commonly for arteriovenous malformations, benign masses, and metastases. Radiosurgery offers patients an effective treatment of life-threatening lesions with a reasonably low risk for discomfort and injury. In the 1990s, the procedure was used widely as primary and adjuvant treatment. The difficulty of defining the boundaries of primary brain cancers makes determining treatment targets problematic. Better imaging and computing offer a bright future for the technology. PMID- 11770297 TI - Novel chemotherapeutic approaches to brain tumors. AB - In reviewing the numerous investigational drug trials for patients with anaplastic gliomas over the past 20 years, it would be fair to say that there have been more than a few disappointments and that the real impact of many of these therapies on patients' duration and quality of survival has been minor at best. It is also fair to state that there has been progress in developing new types of chemotherapy and other agents, in devising new treatment strategies, and in gaining a deeper understanding of the problems that must be overcome to treat patients with anaplastic gliomas successfully. The past several years have seen the realization that oligodendroglioma, primary CNS lymphoma, and medulloblastoma are sensitive to chemotherapy treatments. It is hoped that future studies will delineate better the optimal use of chemotherapy for these tumors. PMID- 11770298 TI - Strategies using the immune system for therapy of brain tumors. AB - Phase II immunotherapy and gene therapy studies should be pursued because of encouraging results in many phase I studies. Future testing in this field may consider modifications of some of the above-mentioned combined strategies. For instance, in the immunization and adoptive transfer studies performed by Holladay et al and by Plautz et al, the systemic adoptive transfer could be altered to intratumoral placements of effector cells. This permutation may be more efficacious because local adoptive immunotherapy approaches involve placement of effector cells where they are needed. Additionally, new avenues of gene therapy are being explored that may offer added beneficial effects for immunization, local or systemic adoptive immunotherapy, or combined chemotherapy and adoptive immunotherapy of tumors. With new genetic tools, such as microarray analyses, SEREX, and creation of cDNA libraries from tumor cells, significant progress in the treatment of neoplasms in the immunologically privileged brain should be forthcoming. PMID- 11770299 TI - Familial neurogenic tumor syndromes. AB - Cancer caused more than 0.5 million deaths in the United States in 2000. This estimate includes patients who have a genetic predisposition to neoplastic disease, including brain neoplasms. Familial tumor syndromes are important to identify clinically because family members require high degrees of monitoring and genetic counseling. Study of these individuals and families has led to the discovery of genes that are an intrinsic aspect of cell regulation and will continue to be relevant in defining mechanisms of neoplastic development in brain and other tissues. PMID- 11770300 TI - Diagnosis and management of brain metastases. AB - In the past 15 years, significant advancement has been made in the diagnosis and treatment of brain metastases. The distinction between the management of single and multiple brain metastases is an important one. Although radiotherapy remains a mainstay of treatment, especially in multiple brain metastases, surgical resection and stereotactic radiosurgery also have their place in the management of selected patients. Rarely, interstitial radiation or chemotherapy also may be used to treat brain metastases in the setting of relapse. PMID- 11770301 TI - The clinical spectrum and pathogenesis of paraneoplastic disorders of the central nervous system. AB - Paraneoplastic neurologic disorders (PND) refer to neurologic disorders of unknown cause that occur at higher frequency in patients with cancer than in the general population. There is increasing evidence that many of these disorders are immune mediated and associated with cytotoxic antitumor immunity. The identification of the immune responses in these patients facilitates the diagnosis of the PND and has led to the cloning and characterization of the target antigens in the nervous system and tumor. PMID- 11770302 TI - Genetics of nervous system tumors. AB - Genetic aberrations are being defined for the various glial tumors. Astrocytic tumors can evolve by two different pathways. The genetic aberrations now being defined for these two pathways are different and can be associated with the grade of malignancy. In oligodendrogliomas, the genetic lesions differ from the astrocytic tumors, and several markers have been linked to chemosensitivity response and survival. Genetic aberrations in ependymomas also differ from the astrocytic tumors or oligodendrogliomas. Although additional cases are needed to study the genetic aberrations, the abnormalities identified suggest that spinal cord tumors carry different markers than intracranial tumors and that the markers within the cranium may be different based on their location. PMID- 11770303 TI - Molecular biology of nervous system tumors. AB - Many genetic alterations that contribute to CNS tumorigenesis and progression have been identified. One goal of such studies is to identify loci that would serve as diagnostic prognostic markers or both. A significant advance is the observation that chromosome 1p loss identified anaplastic oligodendroglioma and a subset of high-grade glioma patients who responded to chemotherapy and had longer survival times. Combined 1p and 19q loss was a predictor of prolonged survival of patients having pure oligodendrogliomas. Such markers eventually may be used to identify patients upfront who would benefit from treatment, while sparing patients who would not benefit. Although many molecular participants involved in the biologic pathways that promote proliferation, angiogenesis, and invasion have been elucidated, there are still many gaps in clinicians' knowledge. It is expected that the use of the human genome project information and databases such as SAGEmap, in combination with techniques such as cDNA arrays and proteomics, will facilitate greatly the identification of novel genes that contribute to CNS tumors. cDNA arrays and tissue arrays will permit the construction of CNS specific screening tools that will permit the identification of tumor-specific mutations and alterations so that patient-specific therapies can be designed. PMID- 11770304 TI - [Endothelin-1 in coronary artery disease]. AB - Endothelins (ETs) are the peptides made up of 21 amino acids synthesized and released by variety of cells. Following studies revealed three isoforms of ETs-ET 1, ET-2 and ET-3. Endothelin ET-1 is known as the most potent endothelium-derived vasoconstrictor peptide identified so far. Endothelin ET-1 acts in a paracrine manner on the two types of receptors ET-A and ET-B. The former is responsible for the vascular smooth muscle constriction and the latter for vasodilation or vasoconstriction depending on the subtype of this receptor (ET-B1 or ET-B2 respectively). Endothelin receptor subtypes have been demonstrated and pharmacologically characterized in the coronary vascular bed. A good deal of experimental and clinical data has been accumulated to support an important role of endothelin-1 in ischemic heart disease. In experimental animals, exogenous ET 1 was found to cause coronary vasoconstriction and, at higher doses, ventricular fibrillation and death. The plasma levels of immunoreactive endothelin-1 were found to be increased in patients with coronary arteriosclerosis, acute myocardial infarction, and angina. The purpose of this study was to critically review the experimental and clinical data supporting the involvement of ET-1 in ischemic heart disease. PMID- 11770305 TI - [Results of coronary artery bypass grafting in patients with impaired left ventricular systolic function]. AB - The purpose of this study was to examine the early and late results of CABG in patients with left ventricular ejection fraction (LVEF) lower than 40%. This study comprised 128 patients (114 male and 14 female) at age from 41 to 75 years (mean 58.3 +/- 7.9). Before operation 115 patients (89.8%) were in CCS class III or IV. Before operation in all patients coronary arteriography with left-sided ventriculography were performed. In 12 patients myocardial perfusion in SPECT with Tc-99m-MIBI was assessed. Perioperative mortality in whole group was 12.5% (16 patients). The lowest (9.2%) was in subgroup with LVEF from 0.31 to 0.4 and the highest (27.3%) in patients with LVEF below 0.2. In 8 patients death was caused by low cardiac output, in 4 by ventricular fibrillation, in the others by renal failure or cerebral stroke (2 patients in each). In 45 patients (35.2%) postoperative low cardiac output was observed. In 41 patients was treated with the use of intraaortic balloon pumping (IABP). Twenty seven (65.9%) patients with IABP survived. During follow-up died 5 pts. 24-months probability of survival calculated from Kaplan-Meier method was 82.4%. In follow-up 80.9% of patients were in CCS class I and II. In SPECT, four months after CABG significantly more segments of left ventricle with normal perfusion (45% vs 53%; p < 0.05) were observed. Patients with LVEF < 40% are at higher operative risk because of often postoperative low output syndrome. Low output syndrome can by successfully treated with IABP. CABG significantly improves circulatory sufficiency in patients with LVEF < 40%. PMID- 11770307 TI - [Generation of reactive oxygen species by peripheral blood neutrophils in patients with pulmonary tuberculosis]. AB - Oxygen metabolism of neutrophils was measured using chemiluminescence method in patient with pulmonary tuberculosis. Patients were included into three groups. Group I--20 patients (10 men, 10 women) aged 24-74 years (mean 48.3 years) with pulmonary tuberculosis BK(+). Group II--20 patients (15 men, 5 women) aged 19-67 years (mean 45.1 years) with pulmonary tuberculosis BK(0). The control group consisted 16 clinically healthy persons (12 men, 4 women) aged 28-59 years (mean 42.5 years). Blood samples (5 ml) were collected for examination from cubital vein early morning before breakfast. A luminometer 1251 coupled with an IBM PC AT compatible computer was used for the measurement of chemiluminescence. The chemiluminescence of non-stimulated neutrophils and those stimulated by a receptor stimulus formyl-Met-Leu-Phe (fMLP) as well as an extrareceptor stimulus phorbol myristate acete (PMA) was measured. The results of our study demonstrated that chemiluminescence of non-stimulated as well as stimulated by fMLP and PMA neutrophils was lower in comparison to the values of chemiluminescence in the control group. PMID- 11770306 TI - [A role of serum ferritin estimations in continuous ambulatory peritoneal dialysis patients]. AB - The aim of our studies was to establish an aspect of pathophysiology that is specially indicated by serum ferritin level in continuous ambulatory peritoneal dialysis (CAPD) patients. In 50 CAPD patients serum ferritin level was related to other serum indicators of iron status as well as serum level of C-reactive protein (CRP), peripheral blood morphology (including RBC indices), serum lipid profile, anthropometrical and laboratory parameters of nutritional status, parameters of dialysis adequacy and dietary food intake. In examined CAPD patients serum ferritin concentration was elevated (median 448, range 25-5334 ng/ml). Statistically significant correlations between serum ferritin level and other examined parameters included positive correlation with CRP (r = +0.389) and negative correlation with transferrin (r = -0.462), RBC (r = -0.441), haemoglobin (r = -0.412), haematocrit (r = -0.483), total cholesterol (r = -0.580) and LDL cholesterol concentration (r = -0.442). There were also positive correlations with daily effluent volume and dietary food intake. Our studies show that in CAPD patients an elevated serum ferritin level is an indicator of inflammatory status, protein malnutrition, and inadequate erythropoiesis, despite normal or nearly normal mean levels of other serum iron parameters. On the other hand, serum ferritin level increases with greater food intake. PMID- 11770308 TI - [Estimation of plasma malonyl dialdehyde concentration in patients with pulmonary tuberculosis]. AB - Plasma malonyl dialdehyde (MDA) concentration was determined by Placer method in patients with pulmonary tuberculosis before and during treatment period with tuberculostatic drugs. Patients were divided into three groups. Group I comprised 20 patients (10 men and 10 women) aged 24-74 years (mean 48.3 years) with pulmonary tuberculosis BK(+). Group II comprised 20 patients (15 men and 5 women) aged 19-67 years (mean 45.1 years) with pulmonary tuberculosis BK(0). The control group consisted of 16 clinically healthy persons (12 men and 4 women) aged 28-59 years (mean 42.5 years). In patients blood samples (5 ml) were collected for examination from cubital vein before, after 1-month and 2-month treatment period with tuberculostatic drugs. In the control group blood samples were collected from cubital vein once. Results of our study showed that plasma MDA concentrations in patients with pulmonary tuberculosis, both before and during treatment period with tuberculostatic drugs, were significantly higher, in comparison to the control group. PMID- 11770309 TI - [Frequency of complications after transthoracic fine-needle biopsy of lung tumors]. AB - Transthoracic fine-needle biopsy (TFNB) is a valuable method of recognizing changes in lungs, especially suspected of cancer. Such operations are cheap, don't demand expensive instruments and are possible to perform in each pneumonology ward, especially if they are an ideal supplement for bronchofibroscoping examination. The possibility of quick and effective performance of transthoracic biopsy shortens the diagnostics considerably. From January 1997 to April 1999 there were performed 406 operations of TFNB. There were 334 people operated on (294 men--74.5%; 85 women--25.5%), average age for the whole group of patients--62.8 (+/- 10.4 years). The patients were divided into two groups considering hospitalization places: I--patients from (not transported for operation)--135 (40.4%), II--patients transported for operation from another hospitals--199 (59.6%) The examination was performed under control of rtg apparatus (7600 OEC Medical System with mobile x-ray tube on a C-arm and laser localizer). The usual complication was an pneumothorax--52 cases (12.8%); drained--16 cases (3.9%). An average depth of inserting in an early pneumothorax is 6.56 (+/- 0.73), in a late pneumothorax--8.6 cm (+/- 1.75), (p = 0.0015). An average depth of inserting in a drained pneumothorax was 8.9 cm (+/- 2.17), in a non-drained pneumothorax 7.7 cm (+/- 1.3) (p = 0.024). Patients that had to be transported for the operation had pneumothoraxes that needed to be drained considerably more often: 14 cases in 199 comparing to 2 in 135 among patients not demanding to be transported (p = 0.02). Pneumothoraxes appeared more often after indicating tumors of smaller size, from 3 cm--21.6%; 3.1-6 cm--13.3% (p = 0.036). From another complications one could notice: hemoptysis--4 cases; subcutaneous emphysema--1 case; fever and shivers--1 case; hypotonia--2 cases; cough--1 case. Those complications were treated symptomatically or vanished themselves. PMID- 11770311 TI - [Experimental closure of bronchial stump after pneumonectomy with the greater omentum]. AB - Authors present their results with experimental closure of bronchial stump after pneumonectomy with pedicled flaps of the greater omentum in sheep. In the experimental group left thoracotomy and laparotomy was performed. The left lung was resected and the bronchial stump was closed with the pedicled flap of the greater omentum. In controls standard left pneumonectomy was performed. After different periods of time (1-12 weeks) the animals were sacrificed, the bronchial stumps were excised and submitted to pathological studies. In none case bronchial fistula occurred. Pathological studies showed that the omentum at the base of the bronchial stump was transformed in the fibrous tissue. The bronchial epithelium begins to cover the omentum in 4 weeks after the operation and this process is finished in 12 weeks after the operation. Pedicled flap of the greater omentum seems to be useful in surgical treatment of bronchial fistulas. PMID- 11770310 TI - [Alpha-fetoprotein--diagnostic utility in squamous cell carcinoma of the head and neck]. AB - The authors present results of evaluation of alpha-fetoprotein (AFP) in 146 persons (108 patients with head and neck carcinoma and 38 healthy persons as control group). We analyzed a concentration of AFP in preliminary study and in monitoring depending on clinical advances of tumour, mass of primary tumour and metastases to lymph nodes. Our results indicate that evaluation of AFP have not high value in diagnostic procedures and monitoring patients with head and neck carcinoma. PMID- 11770312 TI - [The levels of selected cytokines in patients with colorectal cancer--a preliminary report]. AB - The aim of the study was to examine the frequency of the increased serum levels selected cytokines (IL-4, IL-6, IL-8, IL-10) in colorectal cancer and correlation their concentrations with stage of the tumour. The study was done on group consisted of 30 diagnosed colorectal cancer patients, with different location and stage of the tumour. Dukes described the used classification of stage of the tumour. The results were compared with control group consisted of 10 healthy persons. The cytokines were assayed by ELISA method (R&D Systems Minneapolis). In colorectal cancer group the serum levels of IL-6 were increased 3.5 times, IL-8- 5 times and IL-10--13 times in comparison with control group. The serum levels of IL-6 and IL-8 increased with stages of the tumour, whereas IL-10 only in stage D. The serum levels of IL-4 were never elevated. This results permit for further study on usefulness of IL-6, IL-8 and IL-10 as a markers for colorectal cancer in clinical use. PMID- 11770313 TI - [The activity of cathepsin B in colorectal adenocarcinomas]. AB - The aim of the present study was to evaluate the activity of cathepsin B in 36 colorectal adenocarcinomas at stage pT3 of clinical advancement and histological grade G2. A correlation was also analysed of cathepsin B activity with the stage of anatomo-clinical advancement and the presence of chosen anatomo-clinical features of the tumour. Statistically significantly higher activity of cathepsin B was observed both in the cytosol and homogenate of the neoplastic tissue compared to its activity in the cytosol and homogenate of the adjacent unchanged tissue. A tendency was found towards higher cathepsin B activity in homogenate than in cytosol, both in the neoplastic and normal tissue. No correlation was revealed between cathepsin B activity in neoplastic cells and other anatomo clinical tumour parameters analysed. PMID- 11770314 TI - [New method of abdominal cavity opening in surgery of rectum]. AB - The paper presents a new method of surgical access to the small pelvis in which laparotomy is performed by using the transverse incision through both inguinal canals and cutting off the public insertions of the straight muscles of the abdomen. The inguinal canals with the posterior wall were opened according to the Shouldice procedure, and they were closed suturing the public insertions of rectus abdominis, in 8 cases the inguinal canals were repaired by using the Halsted procedure with our modification [1] and in three case our own method was used [2]. From April 28, 1998 to September 06, 2000, 11 operations for rectal carcinoma were performed using this method. Simultaneously, in 5 patients inguinal hernias were repaired. In 6 cases of rectal carcinoma, the abdominoperineal resection of the rectum was performed using the Miles method (in one case accompanied by total hysterotomy, partial ileoectomy and appendectomy, "en bloc"). In 2 cases resection of the rectum using the Hartman method was done. In 2 case the anterior rectal resection by the Dixon method and in another one partial rectalctomy were performed. The abdominal wounds healed by first intension. Among complications showed: difficult healing of the perineal wound was observed in 1 patient, another one required reoperation due to obstruction, in 1 patient inguinal reherniation was found and in another one the hernia around the colostomy occurred. Surgical access suggested by us enables extensive removal of the tissues around the rectum, including adjacent organs (considering easy technical terms), the simultaneous supply of inguinal hernias, in the cases of abdominoperineal resection of the rectum the abdominal anus was created through the left straight muscle of the abdomen, leaving more than 4 cm between a colostomy and an abdominal wound. The low, transverse incision caused only slight surgical discomfort (and patients quickly resumed ambulation) and good cosmetic effect of scar. PMID- 11770315 TI - [Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. AB - Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient. PMID- 11770316 TI - [Influence of interferon-alpha therapy on the count and function of T lymphocytes in children with chronic hepatitis C]. AB - This study aims to assess number and function of T lymphocytes in children with chronic hepatitis persistent C. The study included 60 children with chronic hepatitis C. Among this group 30 were treated with interferon-alpha (INF-alpha) during 6 months. Forty healthy children were included in the study as the control group. We examined subsets of blood lymphocytes T (CD3, CD4, CD8) and lymphocytes with expression of CD3/HLADR, CD3/CD25 antigens using monoclonal antibodies IMK plus and flow cytometry, at the beginning and after 6 months. After INF-alpha therapy a significant increase in subset of CD4 lymphocytes, significant decrease in CD8, increase in CD4/CD8 ratio and increase in lymphocytes with expression CD3/HLADR, CD3/CD25 receptors were observed. Differences in CD8 lymphocytes and CD4/CD8 ratio in the treated children were statistical higher in children with elimination HCV RNA. Applying INF-alpha in children with chronic hepatitis C stimulated immunological response by increasing subsets of CD4 lymphocytes, CD4/CD8 ratio and stimulated lymphocytes. PMID- 11770317 TI - [Evaluation of the precision of the Friedewald's formula for the calculation of low density lipoprotein cholesterol concentration in serum]. AB - The low density lipoproteins (LDL) is one of the important risk factor of coronary heart disease. Evaluation of LDL by direct method of ultracentrifugation (U-LDL), which is the most proper one, is not available in standard laboratories. Instead the Friedewald's formula is commonly used (F-LDL), which calculates level of LDL applying the values of fasting total cholesterol (CH), cholesterol of high density lipoproteins (HDL) and triglicerydes (TG). This formula can be used only in these samples, in which the level TG is below 4.5 mmol/l (400 mg/dl). The aim of the study was the examination of the accuracy of Friedewald's formula while compared with the concentration of LDL cholesterol determined by ultracentrifugation method and evaluate the possibility of extending the range of triglyceride concentration above 4.5 mmol/l (400 mg/dl) in this formula. The data of the study included 2213 samples of the fasting blood serum of consecutive patients in whom the direct measurement of lipoprotein fraction and calculation by Friedewald's formula were performed in years 1992-1999. All serum samples were analysed by the same standardized procedures according to National Heart, Lung and Blood Institute (NHLBI) guidelines. The data of 29 samples with extremely high value of triglyceride level (TG > 5.6 mmol/l, it is 500 mg/dl) were excluded from analysis. The main results showed that agreement between two methods of LDL evaluation was satisfactory also in extended range of TG 4.5-5.6 mmol/l (400-500 mg/dl). The mean values of U-LDL were significant higher than F-LDL (by mean 0.07 mmol/l it is 2.6 mg/dl) in group with TG < or = 4.5 mmol/l, but non significantly lower (by mean 0.13 mmol/l it is 4.9 mg/dl) in group with TG 4.5-5.6 mmol/l. Linear Pearson's and interclass correlations between U-LDL and F-LDL were high and significant in all analyses. PMID- 11770318 TI - [Staphylococcus aureus sepsis--still life threatening disease]. AB - We report an analysis of clinical course of 18 patients presenting with Staphylococcus aureus sepsis. Community acquired infection was caused by Methicillin susceptible S. aureus (MSSA) in 11 patients. MSSA in 3 and Methicillin Resistant S. aureus strains (MRSA) in 4 patients, were the etiologic factor in 7 patients with nosocomial infection. From anamnestic data patients presented with: elevated body temperature--18/18, arthralgia and myalgia--9/18, headache--8/18, nausea--6/18, chills--2/18. Physical examination on admission revealed: meningismus--12/18, hepatomegaly--11/18, purulent and haemorrhagic skin lesions--7/18 and impaired neurological status (Glasgow Coma Scale < or = 12)- 6/18. The mean APACHE III score, calculated from data collected at diagnosis of sepsis was 47 (7-114). Several complications had been observed: endocarditis--10, purulent meningitis--5, focal CNS lesions--5, pneumonia--8, pulmonary abscess--3, hydrothorax--1, abscesses of the spleen--5, renum--4, osteomyelitis--2. 11/18 patients required ICU treatment. Ventilator assistance of respiration was necessary in 7/18. Acute thrombocytopenia (< 100,000/ml) was diagnosed in 60%. In 5 patients suppurative meningitis had been diagnosed with a mean pleocytosis-837 (173-1898) microL. The results of treatment were satisfactory in 11 patients, 3 patients required further surgical treatment (2--cardiosurgery, 1--orthopedic surgery), 4 patients died. Infection caused by community acquired MSSA strains had been characterized by severe clinical course with increased incidence of endocarditis, organ failure and abscess forming. We conclude that Staphylococcus aureus sepsis is still a life-threatening disease, which should be treated at centers with immediate access to imaging techniques of CNS and circulatory system as well as intensive care and cardiosurgery. Community acquired S. aureus sepsis compared with nosocomial infection is characterized by more severe clinical course and higher mortality, despite of a great susceptibility to most antibiotics of causative S. aureus strains. PMID- 11770319 TI - [Endosonography of the rectum and other imaging methods in the diagnosis of bowel inflammatory diseases]. AB - This paper presents the usefulness of rectal endosonography in the diagnostics of the rectal wall and anorectal lesions in patients with inflammatory bowel diseases, mainly with Crohn's disease. Value of endosonography, computed tomography and magnetic resonance imaging were compared. PMID- 11770320 TI - [Chronic pancreatitis as a risk of pancreatic cancer]. AB - The epidemiologic and clinical studies and the results of investigations on molecular level in aspect of the risk of pancreatic cancer in patients suffering from chronic pancreatitis are presented. The risk of pancreatic cancer is significantly elevated in subjects with chronic fibrous pancreatitis. PMID- 11770321 TI - [Sepsis--continual pathogenetic, diagnostic and therapeutic problem]. AB - Sepsis is defined as systemic inflammatory response syndrome (SIRS) caused by infection. Massive activation of humoral and cellular mechanisms of host defense is present and can lead to a multiple organ dysfunction syndrome. Sepsis is good example, that inflammation binds with considerable energetic and metabolic effort of organism i.e. demand for oxygen, protein and microelements. The effort during SIRS exceeds compensatory abilities of organism, cause shock and death. The high mortality (40-70% in the case of septic shock) is a good illustration of the therapeutic problem. In the paper pathogenesis, diagnosis and therapy of sepsis was described. Pathogenetic importance of intoxication was explained--massive intoxication (for example by Staphylococcal enterotoxin) without infection cans lead to SIRS too. Precious advice in selection of antibiotic were given. Advantage penicillins and karbapenems over cephalosporins result from binding to PBP 2 or 1, considerably smaller release of free endotoxin and smaller induction Jarish-Heixhaimer's reaction. The side effect stimulates inflammation and deepens SIRS by release toxins and increase of TNF-alpha. PMID- 11770322 TI - Prince Hal's play as prelude to his invasion of France. PMID- 11770323 TI - The death drive: psychic construction or destruction? PMID- 11770325 TI - Stealing beauty: an exploration of maternal narcissism. PMID- 11770324 TI - Spiritual implications of psychodynamic therapy: immaterial psyche, ideality, and the "area of faith". PMID- 11770326 TI - Increase in tumour necrosis factor-alpha and a change in the lactate dehydrogenase isoenzyme pattern in plasma of workers exposed to aflatoxin contaminated feeds. AB - Six types of animal-feed ingredients and swine mixed feeds from factories in northern Thailand were sampled for analysis of mycotoxins. Mycotoxins found in foodstuffs included aflatoxins, fumonisins, ochratoxins, T-2 toxin, vomitoxin and zearalenone. Samples of airborne dust generated while handling animal feed were collected and analysed to assess exposure of workers to aflatoxins. The average aflatoxin level in the control air samples was 0.99 ng/m3. Higher levels of aflatoxins were found in the air samples taken by samplers attached to five workers adding hydrated sodium calcium aluminosilicate to animal feed (group 1; 1.55 ng/m3) and five workers adding glucomannan to animal feed (group 2; 6.25 ng/m3). The exposed workers showed a change in lactate dehydrogenase isoenzyme activity and tumor necrosis factor-levels in plasma. These changes may be associated with inhalation of mycotoxins and other contaminants in foodstuff. Occupational exposure to mycotoxins and mycotoxin adsorbents needs further evaluation in order to set up a proper system for long term surveillance of exposed population. PMID- 11770327 TI - Interlaboratory study into the proficiency of serum cholinesterase activity measurement. AB - The measurement of cholinesterase activity is an important function of a clinical laboratory. Participation in appropriate quality assurance schemes is essential in ensuring a high analytical standard. Samples of human serum were distributed to thirty-five laboratories for the measurement of cholinesterase activity. Because of methodological differences between the participants, findings of each laboratory were compared either by the use of duplicate samples or by analysis of six mixtures of two samples, one having a high and one a low activity. Of 4,964 distributed samples 95% were analysed and findings reported in 596 reports. Thirty-four percent of all reports were considered very good (less than 5% within run error) and 38% less than satisfactory (within-run error over 10%). Access to a proficiency programme such as this enables laboratories to evaluate the quality of their analytical service. PMID- 11770328 TI - Acute poisoning mortality rate in Plovdiv Region, Bulgaria. AB - The severe recession in Bulgaria which followed the collapse of the totalitarian regime in 1989 had an unfavourable impact on the health status of the population. Systematic studies of acute poisoning mortality rate in the transitional period (1990-98) are scarce in the post-totalitarian Eastern European countries and are lacking in Bulgaria. This retrospective study analysed 1,150 deaths due to acute poisoning in Plovdiv Region for the period 1961-98. Acute poisoning mortality rate was moderately high in the period between 1990 and 1998 with respect to the average of 4.99 per 100,000 a year. It grew steadily during rapid socialist industrialization (1961-90) and showed a trend of slight decrease during transition (1991-1998). The decrease may largely be accounted for by the foundation of the regional toxicological centre and to a certain degree by a drop in industrial and agricultural production and exposure to hazards. PMID- 11770329 TI - Cases of acute poisoning admitted to Clinical Hospital Merkur in Zagreb in 1999. AB - This paper describes 170 cases of acute poisoning in 60 men and 110 women admitted to emergency room from January through November 1999. Ninety-eight percent of acute poisonings were self-inflicted, and 90% occurred at home. Drugs were used in 134 (79%) suicide attempts. Eighty-one acute poisonings were caused by benzodiazepines (48%) and 19 by antidepressants (11%). Alcohol intoxication, alone or combined with the intake of psychoactive drug (28 cases, 16%) predominated in men. Cocaine was the most common narcotic drug, taken by 31 patients (16%). Other acute poisonings involved ecstasy (4 cases), CO (6 cases), and HCl inhalation (2 cases). Previous suicide attempts due to depression were found in 68 patients (40%). Fifty patients (29%) were comatose on admission, 24 were transferred to intensive care, and 3 died. Data such as these can be very useful for handling self-inflicted acute poisonings and for planning long-term health care activities. PMID- 11770330 TI - Organophosphorus compounds and esterases: current research topics concerning the toxicity of and protection against organophosphates. AB - This brief review describes the reactions of organophosphorus compounds with cholinesterases, neuropathy target esterase, and phosphoric triester hydrolases with respect to their toxicity. It also describes antidotes, protectors, and decontaminating agents against organophosphates. PMID- 11770331 TI - In vitro toxicology of heavy metals using mammalian cells: an overview of collaborative research data. AB - The uptake and distribution of selected heavy metals were followed and related to cytotoxicity using various parameters of proliferation and viability of cultured cells. The effects of short-term lead exposure on DNA synthesis were reversible, indicating that lead does not significantly influence genetic cellular function. In contrast, nickel effects persisted, indicating that DNA is one of the main nickel targets. Heavy metals affected all cycle phases, but those related to preparation and commencement of DNA synthesis were the most susceptible. Tolerance appeared in chronic exposure to lead and cadmium. Lead combined with X rays had additive effect, while manganese acted synergistically and appeared to inhibit the DNA repair processes. Zinc and manganese showed a protective effect against the toxic effects of cadmium. Similar antagonistic interaction was seen for nickel v. manganese cytotoxicity. This model system makes it possible to compare heavy metal effects at the cellular level and to identify cellular targets and metabolic processes. PMID- 11770332 TI - [Principles of determining microbiological air quality]. PMID- 11770333 TI - General anaesthesia in rats undergoing experiments on the central nervous system. AB - The rat is one of the species most commonly used in laboratory practice. Numerous publications concerning various aspects of morphology and physiology are based on the results obtained in this species. It make these results comparable and under some precautions enables to transpose into the relationships observed in humans. Each experimental project must obtain the permission of the Local Ethical Committee, as well as comply with the regulations of the European Communities Council, outlined in the "European Convention for the protection of vertebrate animals used for experimental and other scientific purposes". Adequate pre operative care can eliminate or reduce the incidence of many complications, which may occur during anaesthesia. General anaesthesia in experimental practice can be achieved using a variety of drugs and ways of administration, among others inhalational or intravenous. The side effects of anaesthetic agents can be reduced in this way. Knowledge of the effect of anaesthetics on the cerebral circulation, metabolism and intracranial pressure in both normal and pathological conditions is crucial for neurobiological purposes. Many anaesthetic agents depress respiration, which can result in hypoxia, hypercapnia and acidosis. To maintain blood carbon dioxide and oxygen concentration in the physiological range, it is necessary to apply tracheal intubation and artificial ventilation. However, even when using sophisticated equipment, the role of basic clinical observation, such as the colour of the blood shed in the operation field, breathing depth and frequency, cannot be overestimated. The importance of monitoring mean arterial blood pressure and intracranial pressure in experiments on the central nervous system is fundamental. Special attention should be paid to controlling the temperature and monitoring the fluid balance. Appropriate postoperative care can have a decisive influence on the final results of the research. PMID- 11770334 TI - Distribution of efferent neurones innervating the oviduct in the pig. AB - This study was aimed, by means of the retrograde tracing technique, at disclosing the distribution of efferent neurones innervating the porcine oviduct. The fluorescent retrograde tracer Fast Blue was injected into the wall of the right oviduct in six juvenile pigs during laparotomy performed under anaesthesia. After a recovery period of 3 weeks the animals were reanaesthetised, perfused with 4% buffered paraformaldehyde (pH 7.4) and different ganglia, thought to be potent sources of the efferent innervation, were collected. The occurrence and distribution of Fast Blue-positive neurones were studied in the sympathetic chain and prevertebral ganglia, including the coeliac-superior mesenteric ganglion complex, adrenal ganglion, aorticorenal ganglion, ovarian ganglion and inferior mesenteric ganglion. The labelled neurones were found only in the right, ipsilateral ganglia. The largest number of Fast Blue-positive neurones was found in the inferior mesenteric ganglion, ovarian ganglion and in the coeliac-superior mesenteric ganglion complex. In the inferior mesenteric ganglion, the Fast Blue positive neurones showed a tendency to gather in the dorso-cranial and the dorso caudal region of the ganglion, forming two discrete "oviductal centres". The aortico-renal and adrenal ganglion contained a smaller population of Fast Blue positive nerve cell bodies. The smallest number of Fast Blue-positive neurones was found in the sympathetic chain ganglia (T14-L5). The localisation of Fast Blue-positive neurones in the sympathetic chain ganglia and prevertebral ganglia suggests that these nerve structures play a fundamental role in the efferent innervation of the porcine oviduct. PMID- 11770335 TI - Permanent cardiac pacing and its influence on tricuspid valve function. AB - Implantation of transvenous devices is a widespread procedure in clinical cardiology. It is well known that the presence of the electrodes in the cardiovascular system can induce fibrosis or fibrous adhesions between them and cause tricuspid regurgitation. Moreover there are suggestions that the placement of the electrode in the tricuspid orifice may also play a role in the development of tricuspid insufficiency because of the thickening of reactive leaflets and the impairment of their mobility in morphological studies. There are no papers regarding the topography of the electrode in the right ventricle judged by means of transthoracic echocardiography. Moreover in literature we did not meet reports comparing the localisation of the lead on the tricuspid valve function. Therefore we decided to describe the detailed topographic relations between the lead and the structures of the right ventricle in a larger population and we compared the influence of the lead location for tricuspid valve function. Research was carried out on a group of 86 patients (52 M, 34 F), with a mean age of 64.7 +/- 14.9 years with permanent cardiac pacemaker or implantable cardioverter-defibrillator (ICD). On the basis of echocardiograms performed we assessed the position of the lead regarding the tricuspid valve leaflets or commissure, and judged the course of the lead beneath the tricuspid valve level. Moreover special attention was focused on the placement of the tip of the electrode. We qualified its position into three categories: apex of the right ventricle, right ventricle outflow tract, and "para-apex" position. The degree of the tricuspid valve insufficiency was assessed by means of semiquantitative method based on the Color-flow Doppler echocardiography. We measured the extension and the area of the tricuspid regurgitant jet using four-gradual scale. We compared the topography of the lead at the level of the valve with its function by means of the presence and degree of its regurgitation. We stated that in 35% of cases the pacing lead was located at the level of the anterior leaflet of the tricuspid valve, in 23% at the level of the septal leaflet and in 12% at the posterior one. Besides in 10% the electrode was placed between the leaflets just over the commissures. On the other hand in the remaining 20% the lead was positioned centrally in the right atrioventricular orifice without adherence to any leaflet. Next we assessed the course of the lead beneath the tricuspid valve level and stated that most frequently (45%) it run just across the centre of the right ventricle, and in other cases was lying along the interventricular septum (in 39% of cases) or along the anterior wall of the right ventricle (in 16%). The tip of the lead was positioned exactly in the apex of the right ventricle in 74%, in the right ventricular outflow tract in 9% and in 17% its position was "para-apical". We did not see any statistically significant differences between the presence and intensification of valve regurgitation and topography of the lead. We concluded that at the level of the tricuspid valve the lead was positioned in the anteroseptal part of tricuspid annulus and the proper apical position of the electrode's tip occurred in approximately 75% of cases. Localisation of the electrode at the level of the tricuspid orifice does not influence its insufficiency as detected by Doppler echocardiography. PMID- 11770336 TI - The amygdaloid complex of the rabbit--morphological and histochemical study. AB - The aim of the present paper is to describe the morphology and topography of the nuclei of the amygdaloid complex in the rabbit. In the current study we also investigated the intensity of the enzymatic reaction for acetylcholinesterase (AChE) in the amygdaloid complex and the morphology of its neurones. Material consisted of 5 brains of adult New Zealand rabbit, stained either with cresyl violet or for AChE activity. Although, as in other mammals, the rabbit amygdala consists of two main nuclear groups (corticomedial and basolateral), it reveals a peculiar morphology pattern, forming a transition structure between those observed in the cat and rat. Especially characteristic is the arrangement of the basolateral complex. Within that the ventromedial division of the lateral nucleus seems to be the largest, while its dorsolateral division--the smallest. The arrangement of the corticomedial complex in the rabbit is similar to both the cat and rat. In the rabbit the highest acetylcholinesterase activity is found in the basolateral nucleus and the nucleus of the lateral olfactory tract. The lowest AChE staining is observed in the cortical and medial nuclei, amygdalohippocampal and anterior amygdaloid areas and intercalated masses. PMID- 11770337 TI - The anatomy of the tendon of infundibulum. AB - The heart, as we know, is a muscular tissue supported by collagenous structures forming the fibrous skeleton of the heart. A structure by the name of the tendon of infundibulum appeared in the literature with no definite information about its structure or even its existence. The tendon of infundibulum was described as a strip of fibrous tissue structure situated between the aortic root and pulmonary trunk. Our study involved 30, formalin fixed, adult human hearts ranging from 18 to 81 years. Classical macroscopic anatomical methods were applied to observe macroscopically all the connections between the aorto-pulmonary trunk, together with serial transverse histological sections, through roots of the aorta and pulmonary trunk, using eosin-hematoxylin and van Gieson staining. All the hearts seemed to encompass many fascial bands attended by connective tissue. However these fascial bands are not concrete structures and cannot be termed tendons. In our investigation we have been unable to demonstrate macroscopically or histologically any structure which could be significantly approximating to the initial description of the literature. However, as far as we are able to judge, the term tendon of infundibulum has erroneously been introduced into many medical textbooks since the literature cannot still prove its existence. PMID- 11770338 TI - Growth cones in the superior cervical sympathetic ganglion in human foetus aged 23 weeks. AB - Ultrastructural study was conducted on the superior cervical sympathetic ganglia in human foetus aged 23 weeks. It was shown that in investigated foetus the nerve fibres in the ganglion were in different phases of myelination. Also growth cones, which present evidence of still growing fibres, were observed. PMID- 11770339 TI - The middle cardiac vein as a key for "posteroseptal" space--a morphological point of view. AB - About 25% of accessory pathways (AP) run via "posteroseptal" space (PSS). There are three approaches for ablation of these pathways: from the right atrium, from the left atrium or from the ventricle and coronary sinus (CS). However in some cases AP is too far from all of them. Catheterisation of the middle cardiac vein (MCV) seems to be the only chance for successful ablation. Our aim was to evaluate the topography of the MCV in PSS. Classical anatomical investigation was carried out on the autopsy material of 98 consecutive human hearts (42 F, 56 M; age 57 +/- 21 yrs). It was supported by transverse section performed under coronary sinus. Regions just behind the atrioventricular septum and behind the cavities were respectively classified as "septal", right (RP) and left posterior (LP). Between them right (RPS) and left posteroseptal areas (LPS) were present. At the posterior view of the heart the angle between CS and MCV ranged from 75 to 90 degrees in 62% of hearts, 60-75 degrees in 18%, 30-60 degrees in 10% and 90 130 degrees in 10%. In 16% MCV ran via the "septal" region, 59%--LPS, 10%--RPS, 10%--RP and 5%--LP. At the ostium of 58% MCV a valve was observed, however there was no trouble with insertion of the 6F catheter into it. We concluded that it is possible to insert the 6F catheter into MCV, which makes it possible to perform ablation of epicardial postero-inferior accessory pathways. The origin of MCV is usually located in the left "posteroseptal" region and runs towards the left side of the posterior wall. PMID- 11770340 TI - Visualisation of diverticula of the upper part of the alimentary tract; comparison of roentgenologic and endoscopic techniques. AB - Diverticula of the upper part of the alimentary tract, irrespective of their etiology, are frequently observed benign changes of the pharynx, oesophagus, stomach and duodenum. In the present work, patients of the II General Surgery Department of the Medical University of Lublin, with radiologically or endoscopically proved diverticula of the upper part of the alimentary tract, were examined. The presence of diverticula of such localisation was an indication for supplementary endoscopic or radiological examination. The localisation, size, diameter of the opening, mucosal relief of diverticula and its contiguity were checked and analysed. Our data suggest that both medical procedures are complementary to each other. All previously observed changes in diverticula of the thoracic part of the oesophagus and the infradiaphragm part of the alimentary tract were fully proved. The radiological examination gave a better view of Zenker's diverticulum, especially in short and obese patients. Sampling and better visualisation of the diverticula opening testify to the unquestionable superiority of endoscopy. However, precise evaluation by radiological process fully completes the diagnostic protocol. Both diagnostic procedures are usually supplemented by manometric examination of the oesophagus and superior and inferior oesophageal sphincters. This enables the accurate diverticula etiology to be stated. PMID- 11770342 TI - The neuronal structure of the ventromedial and infundibular nuclei in the guinea pig: Nissl and Golgi study. AB - The studies were carried out on the mesencephalons of adult guinea pigs. On the basis of the Golgi technique, as well as the Nissl and Kluver-Barrera methods, four types of neurons were distinguished in the ventromedial nucleus (VMH) and infundibular nucleus (Ni): 1. Rounded neurons (perikarya 12-18 microns) with 3-4 dendritic trunks, which divide once, twice or not at all. The dendritic branches possess varicosities and knob-like spines. These neurons predominate in VMH. 2. Fusiform neurons (perikarya 15-28 microns) with 2 dendritic trunks, which arise from the opposite poles of the cell body. Bead-like protuberances and knob-like processes are observed on the dendrites. These neurons are the most numerous in Ni. 3. Triangular neurons (perikarya 15-22 microns) possess three thick, conical dendrites, which bifurcate dichotomically. Bead-like appendages and knob-like processes were seen on the dendritic surface. 4. Multipolar neurons (perikarya 18 22 microns) with 4-5 dendritic trunks, which are poorly ramified. The dendritic branches are smooth, but varicosities can be observed on their surface. In all types of neurons an axon was observed to arise either from the dendritic trunk or from the soma. PMID- 11770341 TI - Anterior region of the atrioventricular perinodal area in relation to radiofrequency ablation procedures. AB - Atrioventricular nodal reentry tachycardia base on reentry circulation in nodal perinodal area. The radical treatment of choice is radiofrequency ablation. Procedure approached from the anterior-superior (fast) region sufficient a few seconds of energy delivery for success, however this can result in A-V block. The possibility that arrhythmias substrate may lie very superficially (success of ablation) and damage the normal structures (complication) in the perinodal region must be considered. In order to confirm this hypothesis we examined the autopsy material of 100 normal hearts, both sexes from 18 to 105 years of age (control) and 50 hearts with A-V total block 45-95 years of age (block). We paid attention to the morphology of the nodal artery (NA), atrial inputs (AI) and transitional inputs (TI). It was observed that NA at the level of the central fibrous body was positioned in 94% in the central and in 6% in the inferior part of Koch's triangle. It was removed from the endocardium 3-6 mm in control and 2-5 mm in block group respectively (NS). In the perinodal area we distinguished AI that directly joined the A-V compact node: superficial (right part of the interatrial septum) or deep (left part). The former occurred in 100% of controls and in 80% of block groups (NS), and the latter in 80% of control group and in 34% in block respectively (p < 0.05). The real substrate of arrhythmia in anterior-superior region lies very superficially and far from the conduction tissue; NA in examined hearts was lying deep beneath the endocardium; ablation close to the node could result in A-V block. PMID- 11770343 TI - The morphometric parameters of adrenal cortex in sows: in normal condition and after prolactin infusion. AB - The aim of this study was to examine the effect of experimental hyperprolactinemia on the stereological parameters of porcine adrenal cortex. In cyclic sows, after preovulatory luteinizing hormone (LH) peak, porcine prolactin (PRL, 0.3 mg) or saline were administered i.v. for 48 h at 2 h intervals. Next sows were slaughtered and adrenal glands were dissected. Stereological analysis of the left adrenal gland did not reveal any significant differences between control and PRL-treated sows. Experimental hyperprolactinemia did not affect the volume of particular cortical zones, the number and the volume of adrenocortical cells or the average volume of their cell nuclei. Moreover, we present for the first time a detailed stereological description of adrenal cortex in sows. PMID- 11770344 TI - Transverse ligament of the knee in human embryos aged 7 and 8 weeks. AB - The aim of the study was to trace the transverse ligament of the knee in staged human embryos. Investigations were carried out on 42 embryos of developmental stages 18-23 (44-56 postovulatory days) from the collection of the Department of Anatomy in Poznan. It was found that in embryos at stage 19 peripheral condensation of the mesenchymal interzone of knee joint, located anteriorly to the primordia of the cruciate ligaments, was recognizable. Clearly visible cellular primordium of the transverse ligament, connected with the medial and lateral menisci, was observed in stage 22. The primordium consisted of oval cells, arranged into densely packed parallel strands. The cells were greater than those forming the menisci. In embryos at stage 23 all intraarticular elements (articular surfaces, menisci and their ligaments, cruciate ligaments and transverse ligament) of the knee joint were clearly evident. PMID- 11770345 TI - The importance of the anatomy of the splenic artery and its branches in splenic artery embolisation. AB - Splenic artery embolisation can be performed preoperatively in an attempt to decrease thrombocyte destruction, or as an alternative to surgery, to obtain partial or total organ ablation. During this procedure, it is very important to deliver embolising agents distal to the origin to pancreatic branches to avoid the risk of pancreatitis. Therefore, a detailed knowledge of the anatomy of the splenic artery and its branches is required to achieve safe embolisation. The purpose of our study is to measure the average distance between the origin of the last pancreatic branch and the splenic hilum in digital angiograms and cadaver specimens. PMID- 11770346 TI - The radioanatomical research of plural renal arteries. AB - The aim of our study was to evaluate the physiological and pathological variations of plural renal arteries in individuals of various constitutional types. Data about sixty-six renal angiographies obtained post-mortem from 35 traffic accident victims were compared with 68 aortonephrograms of 35 randomly selected patients of the Medical Department. During the autopsy of the traffic casualties no major pathological traces were observed. Out of 35 medical patients, 19 were presented with no signs of renal artery diseases, 14 were diagnosed for stenosis of renal arteries and 2 for diabetes mellitus. Abdominal aortography with following selective angiography was performed. Out of the total of 35 patients examined by method of abdominal aortography with following selective angiography, plural renal arteries (PRA) were observed in 9 cases (25.7%), two of these having a double-sided PRA. Among 19 patients without angiography, signs of renal artery pathologies PRA were present in 5 cases (26.3%). This was also observed in 2 out of 14 patients with RA stenosis (14.2%), and in both diabetic patients. Among 35 examined patients, PRA were found in 25.7% (9 cases), in two of them PRA were revealed on both sides (5.7%). A total of 68 nephrograms was obtained in 35 patients (2 patients had one kidney only). PRA were present in 16.2% (11) of nephrograms. Six (25%) out of a total of 24 men had PRA. Among 11 examined women, PRA were observed in 3 cases (27.2%). Right sided PRA were revealed in 6 out of a total of 35 right kidneys (17.1%) and left sided PRA in 5 (15.2%) out of 33 left kidneys. Among 35 renal preparations taken from corpses of people who died from injures and had no renal or any other pathology, PRA were present in 9 cases (25.7%). PRA were counted in 9 cases (34.6%) of 26 preparations from corpses with advanced arteriosclerosis. Plural kidney arteries were met in 3 cases from 5 preparations taken from diabetic cadavers (60%). PRA were found in 21 (31.8%) cases out of 66 preparations examined by method of post vital angiography. PRA were noticed in 9 (28.1%) cases of 32 right side preparations, and in 12 cases (35.3%) of 34 left side preparations. PRA were observed in 11 cases (30.6%) of 36 male preparations, and in 10 cases (33.3%) of 30 female preparations. Due to the constitutional types of body: in picnic type cadavers and patients PRA were described in 12 cases (36.4%) of a total of 33, in mesomorphic type--in 8 cases (29.6%) of a total of 27, and in asthenic type cadavers--in 1 case out of 10 (10%). Total statistics showed that most often lower pole (50%) and upper pole (16.5%) accessory arteries were observed. Upper pole perforating arteries were described in nearly 22%, but lower pole arteries only in 4.4%. Double renal arteries occurred in 18.7%, and upper pole accessory arteries in 16.5%. Triple renal arteries were found very seldom (nearly 3%). PMID- 11770347 TI - Virtual modelling of the surgical anatomy of the petrous bone. AB - The surgical anatomy of the petrous bone is difficult to learn and to imagine due to the porous structure. Obviously the surgeon's training is based on cadaver dissections as we are still lacking good, versatile models of the temporal bone and its important structures. The clearly visible, rapid development of computer science provides us with new possibilities that should be immediately engaged in modelling and simulating the human anatomy. The virtual, three-dimensional computer model of the bony pyramid was created based on the tomographic x-ray 1 mm slices and evaluated in accordance to its usefulness in learning and planning the neurosurgical approaches to the petrous region. The model was created in the virtual reality markup language, in order to make it available through the Internet. The basic anatomy of the main surgical approaches used in this region was visualised and evaluated in accordance with the real, intraoperative anatomy. The model could be easily accessed through the Internet. It was user-friendly and intuitive. The model seemed to be helpful in planning the basic approaches to the petroclival region. Computer science, with the help of the virtual modelling techniques, gives us a powerful method of learning and training surgical anatomy and approaches, although cadaveric dissection still remains the main point of the surgeon's training. PMID- 11770348 TI - Cleidooccipital muscle: an anomalous muscle in the neck region. AB - During our routine dissection studies, we encountered a case with abnormal muscle deep to the sternocleidomastoid muscle. According to its origin, insertion and innervation features, the abnormal muscle was considered as cleidooccipitalis muscle. PMID- 11770349 TI - 'No change for guidelines on GP prescribing of NHS impotence treatments' (no sex, please, we're new labour). PMID- 11770350 TI - Standby emergency treatment, the 'third option': malaria advice for travellers. PMID- 11770351 TI - Abnormalities of thyroid hormonal function tests in hospitalised elderly patients: a prospective study. AB - We measured thyroidal hormonal function tests in unselected sick and hospitalised elderly patients with a new immunoassay technique. Our results show a significant percentage of subjects with thyroid hormonal dysfunction. PMID- 11770352 TI - The natural history and associations of sleep disordered breathing in first ever stroke. AB - Although the prevalence of sleep-disordered breathing (SDB) in patients following stroke has been found to be high, there are few data about whether these changes persist in the months that follow stroke. The present study aims to confirm the prevalence of SDB following first ever stroke, to investigate an association between SDB and subtype of stroke and to determine the change in SDB three months following a first ever stroke. PMID- 11770353 TI - The relationship between expression of p53/Bcl-2 and histopathological criteria in breast invasive ductal carcinomas. AB - Seventy-five cases of invasive ductal carcinoma (IDC) on whom axillary lymph node dissection and mastectomy were performed between 1996 and 2000 were reviewed histopathologically. The slides were stained immunohistologically with p53 and Bcl-2. In 40 cases we observed 53% Bcl-2 and 69% p53 positivity. There were correlations between p53 and tumour grade, and also between p53 and Bcl-2. We did not observe any connection between the main histopathological prognostic factors- lymph node metastasis, tumour size, tubule formation, pleomorphism--and p53/Bcl 2. In our study, IDC with a high mitotic index and poor differentiation showed mutant p53 positive staining. Expression of Bcl-2 is associated with low nuclear grade and absence of mutant p53. This study was designed to reveal the correlation between histopathological findings and the expression of p53/Bcl-2 on prognosis. PMID- 11770354 TI - Camptodactyly in a neurology outpatient clinic. AB - Camptodactyly is a non-neurogenic flexion deformity of the proximal interphalangeal joint, most commonly affecting the little finger. The frequency of camptodactyly in patients referred to three general neurology outpatient clinics, two in district general hospitals and one in a regional neuroscience centre, over the course of one year (2000) was measured. Five out of 978 consecutive new outpatients (0.5%) had camptodactyly (2 M, 3 F); four had bilateral deformity. In only one was camptodactyly the reason for referral. In two cases, camptodactyly was entirely incidental to the neurological symptoms; in two others it was incidental but might have been confused with the neurological features. In three cases other family members were affected, in a manner consistent with autosomal dominant inheritance with variable penetrance. Camptodactyly is not infrequently observed in the general neurology outpatient clinic. It merits attention in order to avoid confusion with other, neurogenic, causes of clawing, and so avoid unnecessary investigation. PMID- 11770355 TI - Patent foramen ovale in elderly stroke patients. AB - The aim of this study was to determine the incidence of echocardiographically detectable patent foramen ovale (PFO) in elderly patients who have strokes from cerebral infarction, as well as to assess the association between PFOs and other risk factors for stroke disease. Forty-three patients aged > or = 65 years admitted consecutively with cerebral infarction shown on computerised tomography of the brain were assessed using transoesophageal echocardiography. A PFO was present in 8 (19%) of the 43 patients. Four patients (50%) in this PFO group had stroke risk factors. Two were in atrial fibrillation and, of the six patients in sinus rhythm, a risk factor was present in two, both of whom had diabetes mellitus. A PFO was not detected in 35 patients. Twenty-nine (83%) of the patients in this group had risk factors, with 18 having two or more. Seven patients were in atrial fibrillation. Of the 28 patients in sinus rhythm, risk factors were present in 22 (78%). PMID- 11770356 TI - Methanol-induced optic neuropathy: treatment with intravenous high dose steroids. AB - The aim of this study was to find the potential benefit of intravenous high dose steroids in the treatment of patients with methanol optic neuropathy. Four patients complaining of diminution of vision after taking methylated spirit presented to us within a variable period of its consumption. The systemic features of methanol poisoning were absent in these patients. Raised blood levels of methanol confirmed the diagnosis of methanol optic neuropathy. All these patients received high doses of intravenous steroids for three days, followed by oral steroids, 1 mg/kg body weight, for 11 days. The administration of high doses of intravenous steroids led to an improvement of visual status in all four patients. Intravenous high dose steroids benefit the visual status of patients with methanol-induced optic neuropathy, provided the interval between the consumption of methanol and starting treatment is short. Further studies should be undertaken to document the role of intravenous steroids in this context. PMID- 11770357 TI - The surgical management of early breast cancer. AB - Definitive surgical treatment should never be undertaken without a histological confirmation of the diagnosis. For operable disease primary treatment is normally breast-conserving surgery or mastectomy, in association with axillary surgery. Patients with larger technically operable tumours may be treated with primary chemotherapy to try to shrink the tumour so that less radical surgery can be undertaken. The objective of surgery is clearance of local and regional disease with a margin of clear tissue, and to achieve an acceptable cosmetic outcome. Clinical assessment of the axilla is unreliable and because of the prognostic significance of the axillary nodal status this has to be determined histologically. Patients with single tumours < or = 4 cm are suitable for conservation therapy but this will depend on breast size. After excision with clear margins and subsequent radiotherapy the breast recurrence rate should not exceed 5-10% at 10 years. Patients will require mastectomy because of disease extent, breast size, or for personal reasons. The usual operation is a total mastectomy with axillary clearance but small islands of breast tissue may persist subcutaneously as potential sites for future disease. Good breast-conserving surgery is invariably better than reconstruction but, in the event of a mastectomy, reconstruction is offered either as an immediate or a delayed procedure. Complications of any form of surgery include haematoma, wound sepsis and wound flap necrosis. Specific complications are collections of serous fluid in the axilla or in the wound itself (seroma), shoulder stiffness and cording caused by distal thrombosis of lymphatics or veins after axillary dissection. The intercostobrachial nerve is often divided during surgery, causing numbness of the inner upper arm. Some degree of lymphoedema of the arm occurs in 10-15% of patients treated with axillary surgery. It is usually mild and may become rare as more patients have sentinel node biopsies. PMID- 11770358 TI - Radiotherapy for early and advanced breast cancer. AB - Postoperative radiotherapy (RT) forms an intrinsic part of breast conservation therapy, substantially reducing the risk of breast relapse. It is given 4-6 weeks postoperatively using medial and lateral beams to achieve a near homogeneous dose to the breast while minimising the dose to adjacent structures. Typically, a dose of 40 Gy in 15 daily fractions over three weeks or 50 Gy in 25 fractions over five weeks is given, with a boost of 10 Gy using low energy electrons or superficial X-rays. RT is delivered to the chest wall after mastectomy in patients with large tumours (> 5 cm), close surgical margins, or significant axillary node involvement and may result in an additional 10% survival benefit. Early complications of RT include tiredness, skin erythema and moist desquamation. Late reactions, breast fibrosis, telangiectases and peau d'orange are reduced if more treatment fractions are given. Lung irradiation is minimised by careful treatment planning and < 1% of patients experience radiation pneumonitis or pulmonary fibrosis. Patients with locally advanced breast cancer may be offered a combination of systemic therapy, endocrine, chemotherapy and radical RT. Preoperative systemic and radiation therapy reduces the mastectomy rate but at present does not improve survival. Those who are unfit for radical treatment and have large ulcerating or fixed cancers are offered either endocrine or cytotoxic therapy, depending upon the oestrogen receptor status, followed by RT, which is unlikely to cure but may achieve local control for a variable duration. RT forms part of the multidisciplinary approach to palliative treatment for metastatic disease. Bone metastases occur in 75% of women with metastatic disease and RT provides effective pain relief and reducing risk of pathological fractures. Patients with brain metastases need high-dose steroids followed by cranial RT. PMID- 11770359 TI - Is erectile dysfunction a marker for cardiovascular disease? AB - There is now significant evidence that erectile dysfunction (ED) can be a symptom of cardiovascular disease, and can act as a marker for disease progression. National Health Service (NHS) prescribing restrictions on treatments for ED have recently been reviewed by the Department of Health, and current arrangements will not change. Unrestricted availability of licensed treatments for ED on the NHS, irrespective of the cause of the ED, may encourage men to present for investigation, enabling early detection of cardiovascular disease. Sildenafil citrate (Viagra), an effective treatment for ED, can also have a direct beneficial effect on cardiovascular disease. Unrestricted NHS availability of ED treatments such as sildenafil could facilitate greater achievement of National Service Framework targets for coronary heart disease. PMID- 11770360 TI - Non-neurological variables and mortality of acute stroke. AB - Acute stroke is associated with high mortality. While this is the direct consequence of the neurological injury, stroke patients develop a number of physiological abnormalities and complications in the acute phase. Extensive research has produced a plethora of information about these non-neurological variables. Different patients have different abnormalities. Some of these variables have severe adverse effects on mortality, both acute and long term. Some of the variables are pre-existing, while others are non-modifiable. The body responds to cerebral tissue injury in a way that seems to lead to further damage to the brain and other vital systems, and patients usually have more than one variable needing attention. Acute stroke presents as a multisystem disease on the verge of multisystem failure. Although there is lack of evidence of the benefits of correcting the deranged variables, it makes clinical sense that non neurological variables should be identified, monitored and managed, with the aim of improving the outcome of acute stroke patients. PMID- 11770361 TI - Thalidomide: 40 years on. AB - Thalidomide was marketed in the late-1950s as a sedative and tranquilliser of exceptionally low general toxicity, but in 1961 it was implicated separately by Lenz and MacBride as the cause of the epidemic of congenital malformations that had been puzzling the world for some years. It is a very potent teratogen in humans, but in few other mammalian species; damage to the embryo is produced at specific stages of gestation, but the mechanism of embryopathic action is still not understood. Following the withdrawal of the drug worldwide, it was consigned to the history of medical tragedies. In 1965, however, Sheskin discovered that it was effective in treating erythema nodosum leprosum, a distressing complication of leprosy. As the drug is neither an antibiotic nor an analgesic, its action was assumed to be immunosuppressive. In Brazil the drug was used widely with few regulatory controls, since when more than 100 cases of congenital malformation have appeared. Sheskin's discovery led to the experimental use of thalidomide in many other indications thought to possess some immunological component. In some cases, e.g. Behcet's syndrome, graft-versus-host disease and aphthous ulceration in HIV-positive patients, the drug has been shown to possess some efficacy. And there is some evidence that it inhibits the replication of one of the immunodeficiency viruses. The AIDS community in the US has exerted much pressure on the FDA to allow the drug on to the market, although the use of a potent immunosuppressive drug of unknown mechanism in an immunodeficiency condition raises further questions. Thalidomide is not always beneficial; its use is associated with an increased mortality in epidermal necrolysis. In 1991, D'Amato confirmed it possessed antiangiogenic properties and this led to further trials in malignant conditions. Results were mixed, but those in multiple myeloma gave some grounds for optimism. In 1998, the FDA announced its extraordinary decision to grant marketing approval for thalidomide. PMID- 11770362 TI - The echinocandins, first novel class of antifungals in two decades: will they live up to their promise? AB - The echinocandins comprise a major development in systemic antifungal therapy. They rapidly and irreversibly inhibit glucan synthesis in the fungal cell wall, a distinct target from azole antifungals, flucytosine and polyenes. As such, the echinocandins appear effective against triazole and amphotericin B resistant fungi. The spectrum is still not fully understood because of problems with susceptibility testing, and because of limited studies in animal models. The primary target species for clinical studies include Candida and Aspergillus, but the class is likely to have broader use. Lack of nephrotoxicity and few drug interactions make this class attractive. The major limitations at present appear to be the lack of oral formulation and uncertainty regarding the extent of the spectrum. These drugs have the potential of being significant additions to the management of mycoses in the critically ill patient. PMID- 11770363 TI - Convulsive syncope in young adults: think of a cardiac cause. AB - Convulsive syncope is often misdiagnosed as epilepsy because of its similarity in clinical presentation. We present the case of a patient who had several such episodes before a definitive diagnosis was made. The diagnosis of prolonged sinus arrest was finally made with the valuable assistance of cardiac monitoring during a witnessed episode of convulsive syncope. Appropriate therapy was promptly introduced, i.e. temporary then permanent cardiac pacing. It is possible that any further delay in reaching the correct diagnosis and delivering appropriate treatment might have carried a significant risk of morbidity and mortality. Continuous electrocardiographic monitoring performed at an early stage is therefore crucial in the initial assessment of a young adult presenting with convulsive syncope, as a significant proportion may have a cardiovascular aetiology, particularly arrhythmias, for their syncopal episodes. PMID- 11770364 TI - Bilateral Dupuytren's contracture in a black patient. AB - The first case of Dupuytren's contracture in a black patient with no obvious caucasian admixture was reported in 1979. This condition is rare in the purely black population and since 1979 only 23 cases have been reported. We present the case of a black man with no history of caucasian admixture with bilateral Dupuytren's contracture. We suggest that this condition may not be as rare as the literature suggests and, that canvassing other hand societies for their experience, particularly in the continent of Africa, may help to establish the true incidence of this condition. PMID- 11770365 TI - Concurrent myelitis and Guillain-Barre syndrome after varicella infection. AB - Myelitis and Guillain-Barre syndrome occurring concurrently after varicella infection is very rare. A 34-year-old man presented with progressive flaccid tetraparesis, facial palsy, respiratory failure, sensory loss and urinary incontinence one week after varicella infection. Clinical, imaging and electrodiagnostic studies supported the diagnosis of myelitis and Guillain-Barre syndrome. He improved with intravenous acyclovir and gammaglobulin. PMID- 11770366 TI - Repair of concomitant inguinal and femoral hernias under local anaesthesia. AB - We describe the case of a 91-year-old patient with small bowel obstruction due to an obstructed groin hernia. It was decided to repair the hernia under local anaesthesia and sedation because of the patient's age and medical condition. At surgery, concomitant inguinal and femoral hernias were found and repaired. We discuss the technique of repairing groin hernias under local anaesthesia, especially in the elderly, and the previously reported incidence of concomitant hernias. PMID- 11770367 TI - Complete resolution of refractory immune thrombocytopenic purpura after colectomy for ulcerative colitis. AB - Immune thrombocytopenia (ITP) is a destructive thrombocytopenia caused by an autoantibody directed to platelet membrane antigens. Various immunological diseases have been associated with ITP, but an association between inflammatory bowel disease (IBD) and ITP is not well recognised. We report a case of refractory immune thrombocytopenia associated with ulcerative colitis that resolved after colectomy. Although the medical treatment of inflammatory bowel disease or splenectomy are usually enough to treat ITP, it may be necessary to do a colectomy in refractory patients. PMID- 11770368 TI - An unusual case of left paraduodenal hernia. AB - Paraduodenal hernias are the commonest form of intra-abdominal hernia. We report on a rare paraduodenal hernia involving the duodenojejunal recess. PMID- 11770370 TI - [Radiotherapy outside of oncology. When is it indicated? (interview by Waltraud Paukstadt)]. PMID- 11770369 TI - The use of intravascular ultrasound imaging for the assessment of left main stem coronary disease before bypass surgery. AB - Coronary angiography has well-known limitations in the assessment of coronary artery disease, many of which are overcome using intravascular ultrasound (IVUS). While these limitations are particularly pronounced in the left main stem coronary artery, it is in this anatomical location that a correct decision regarding treatment modality has the most prognostic relevance to the patient. In this case report we demonstrate the importance of considering IVUS imaging in patients with apparent ostial and proximal left main stem disease before coronary bypass surgery. PMID- 11770371 TI - [Risky high blood pressure, lipid and blood glucose values. Are blood pressure patients underserved?]. AB - It is now generally accepted that the prognostic relevance of diastolic and systolic blood pressures varies with age. The probable explanation for this is considered to be the age-related hemodynamic changes in central and peripheral arteries. An analysis of 47,000 hypertensives reveals that a therapeutic strategy focused merely on lowering elevated blood pressure is inadequate. Since most hypertensives have multiple risk factors that are readily identifiable and treatable, a multifactorial therapeutic strategy is needed. Accordingly, modern treatment of hypertensives implies a predominant role for risk factor management. A European study on secondary prevention documents an unacceptably high prevalence of unhealthy lifestyles and poorly controlled blood pressure, lipid and glucose levels in patients with clinically diagnosed CHD. It is high time that scientific investigations be carried out to identify the reasons for the inadequate practical implementation of evidence-based preventive and therapeutic measures. It is to be expected that epidemiological investigations will help provide relevant data. PMID- 11770372 TI - [Renal failure and cardiovascular risk. Increased borderline serum creatinine--a warning sign?]. AB - It is well-known that patients with terminal renal insufficiency are at increased risk for a future cardiovascular event. A relevant relationship also appears to apply to the early stages of renal insufficiency. The HOPE study has shown that the incidence of myocardial infarction, apoplexy and cardiovascular mortality in patients with incipient renal insufficiency is significantly raised. The study also found that the incidence of cardiovascular events is in direct proportion to the level of serum creatinine. Against this background, patients at risk can be readily identified. The HOPE study documents a considerable cardiovascular risk for patients with incipient renal insufficiency and concomitant uncomplicated hypertension, atherosclerosis or diabetes. In view of this, the use of ACE inhibitors in patients with moderate renal insufficiency should now be introduced. In the HOPE subjects, ramipril was found not only to lower the cardiovascular risk, but also to improve renal insufficiency. PMID- 11770373 TI - [Lowering blood pressure in obese hypertensive patients. Which antihypertensive drugs are suitable]. AB - Current guidelines in the treatment of arterial hypertension do not recommend differential treatment of obesity-associated hypertension. Since optimal blood pressure control in most obese hypertensives requires a combination of blood pressure-lowering substances, careful consideration of the choice of treatment is of particular importance. On the basis of their favorable metabolic properties, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and low dose diuretics, should be preferentially employed in the obese. Beta-blockers should not be given to young obese patients with uncomplicated hypertension. Before definitive pronouncements on what constitutes optimal treatment of obese patients can be made, the results of studies looking at hard end points must be available. PMID- 11770374 TI - [The most severe heart failure. Assisted pumping halves fatalities]. PMID- 11770375 TI - [Emergencies in general practice. Gynecological bleeding]. PMID- 11770377 TI - [Sudden painful joints accompanied by 2 red ears]. PMID- 11770376 TI - [Fewer problems with fibromyalgia patients. Prescriptions in therapy frustration]. PMID- 11770378 TI - [Preventive influenza vaccination. Physicians often fail to think of themselves]. PMID- 11770379 TI - [200,000 Germans were screened for vascular risk. Every third atrium fibrillated undisturbed]. PMID- 11770380 TI - [Instead of expensive infusion therapy, ambulatory phytotherapy in tinnitus treatment]. PMID- 11770381 TI - [Not only plasma viral load counts. HIV can also be latent in the brain]. PMID- 11770382 TI - [Acute exacerbated bronchitis. New guidelines for choice of antibiotics]. PMID- 11770383 TI - [Leukotrienes. Interlopers on trips to the park]. PMID- 11770384 TI - [Beta blockers in heart failure administered with too much reticence. Longevity sacrificed]. PMID- 11770385 TI - [Experimental pharmacotherapy in sensitization to the effects of opioids]. AB - Sensitization is a phenomenon which might contribute to addiction and psychic dependence. Contrary to tolerance, sensitization is characterized by increased behavioural response after repeated administration of a drug. This article reviews findings on experimental treatment of sensitization to opioids measured mostly by changes of locomotion in mice and rats and considers possible neurobiological mechanisms of sensitization to opioids. A number of drugs affecting opioid, dopaminergic, glutamatergic, gabaergic and serotoninergic systems have been tested in experimental therapy and prevention of sensitization to opioids. However, none of the substances tested until now has proved to be perfect in this respect. On the other hand, there are substances that seem to be promising for treatment or prevention of sensitization to opioids, but have not been tested as yet. PMID- 11770386 TI - [The chaos theory and physiology of the heart]. AB - Chaos theory was received with the great enthusiasm. It has provided a new, attractive approach to irregular, nonperiodic phenomena: apparently stochastic behaviour might be explained by a few nonlinear differential equations. During the last years, it became clear that chaos in the exact sense is hardly to be proved in real systems, such as the cardiac dynamics. Despite this fact, new methods, originally developed for chaotic signals, are successfully applied to fetal ECG extraction, noise filtering and heart dynamics modelling. PMID- 11770387 TI - [Zinc and its role in the regulation of cell death]. AB - Zinc is a key element for maintenance of the structural and functional integrity of eukaryotic cells and tissues. In living systems, it forms stable complexes with macromolecules as well as so called labile pools called zincosomes, which are nowadays considered crucial for the regulation of apoptosis and cell proliferation. Zinc may block apoptosis induced by many external factors by inhibiting caspases and endonucleases, through interactions with transcription factors and kinases or due to its antioxidant activities. On the other hand, depletion of zinc may lead to rapid activation of apoptotic cascade and consequent cell death in many types of cells. Imbalances in intracellular zinc pools lead to improper regulation of cell death and proliferation, which is often causing or accompanying diseases. Therefore, detailed elucidation of the role of zinc in these regulations presents a solution for various pathophysiological conditions. PMID- 11770388 TI - [The founding and beginnings of the Institute of Physiology at the Medical School of Comenius University in Bratislava (1924-1939)]. AB - The article deals with the history of foundation and beginnings of the Institute of Physiology of the Medical Faculty of Comenius University in Bratislava. In the school year 1924/25, after the Czechoslovak state university had been founded, the Physiological Institute began its work. The first director was prof. MUDr. Antonin Hanak. Under his leadership the basis of pedagogical and scientific activities in the Institute was established. In the school year 1926/27, Institute moved into the newly built rooms in Sasinkova street No 2, where it has been located ever since. Professor Hanak had been working in Bratislava since 1924 till 1930. After his walk-off to Praha, professor MUDr. Vilem Hons became the head of the Institute. In the school year 1936/37 he was elected the dean of the Medical Faculty of Comenius University. He worked in Bratislava till 1939, when he was suspended from the service in the Slovak schools. Both Czech professors founded firm basis of physiology as a subject matter and as a scientific discipline in Slovakia. PMID- 11770389 TI - Do women have more adverse drug reactions? AB - Up to 5% of all hospital admissions are the result of adverse drug reactions (ADRs). Identifying those factors which may predispose to ADRs is essential for risk management. Amongst the known risk factors for adverse reactions are increasing age, polypharmacy, liver and renal disease as well as being female. Female patients have a 1.5- to 1.7-fold greater risk of developing an ADR, including adverse skin reactions, compared with male patients. The reasons for this increased risk are not entirely clear but include gender-related differences in pharmacokinetic, immunological and hormonal factors as well as differences in the use of medications by women compared with men. Women generally have a lower lean body mass, a reduced hepatic clearance, have differences in activity of cytochrome P450 (CYP) enzymes (40% increase in CYP3A4, varied decrease in CYP2D6, CYP2C19 and CYP1A2), and metabolize drugs at different rates compared with men. Other important factors include conjugation, absorption, protein binding and renal elimination, which may all have some gender-based differences. However, how these differences result in an increased risk of ADRs is not clear. There are pharmacodynamic differences between men and women, seen particularly with cardiac and psychotropic medications. There is no doubt that chlorpromazine, fluspirilene and various antipsychotics appear more effective in women than men for the same dosage and plasma concentration. Similarly, women are at increased risk of QT prolongation with certain anti-arrhythmic drugs compared with men even at equivalent serum concentrations. The mechanisms are unknown. Increasingly the evidence is that idiosyncratic drug reactions, particularly cutaneous reactions, appear to have an immunological etiology. It is possible that gender difference in T cell activation and proliferation account for this as well as the increased prevalence of skin diseases such as systemic lupus erythematosus and photosensitivity. Whatever the mechanism(s), it is important to be aware that gender is a significant factor in ADRs. PMID- 11770390 TI - Occupational contact dermatitis. Recognition and management. AB - Occupational contact dermatitis (OCD) represents 90 to 95% of all occupational dermatoses. The incidence rate of OCD is estimated to be around 0.5 to 1.9 cases per full-time worker per year. However, epidemiologic data are lacking and incidence is probably underestimated, especially in the US. Over the past 20 years, OCD has been the most frequently reported occupational disorder to German social insurance institutions. Critical factors in the management of OCD are recognition of clinical features, knowledge of allergens and irritants present in different occupational fields, knowledge of suitable protection, interpretation of patch test results, and awareness of medicolegal aspects. Management of OCD should be carried out by dermatologists and patch test clinics in cooperation with physicians specialized in industrial medicine. Individuals at high risk of OCD are hairdressers, dental laboratory technicians, other healthcare workers, construction industry workers, metal workers, leather and shoe manufacturers, florists and gardeners, and bakers, caterers, confectioners and cooks. PMID- 11770391 TI - Immunomodulating drugs in the management of psoriatic arthritis. AB - Psoriatic arthritis is a chronic inflammatory arthropathy which can be distinguished from rheumatoid arthritis on the basis of differing patient demographics, genetic predisposition, histopathologic change, radiographic appearance, and clinical course. The cause of psoriatic arthritis remains unknown but appears to be autoimmune in nature as its pathogenesis is characterized by persistent synovial inflammation resulting in damage to the articular cartilage and osteolysis. Compared with rheumatoid arthritis, distinct lymphocyte subpopulations and pro-inflammatory cytokine levels appear to be present within the joint but the importance and therapeutic implications of these differences is uncertain. The clinical presentation of psoriatic arthritis is variable and overlapping patterns of joint involvement affecting both the appendicular and axial skeleton are seen. For patients with mild synovial disease and a favorable prognosis, the use of a nonsteroidal anti-inflammatory drug for symptomatic relief is often sufficient. However, the destructive potential of psoriatic arthritis is increasingly recognized and patients with more synovial disease and radiographic change at presentation appear to be at risk for greater morbidity and increased mortality. Immunomodulating therapy has the potential to suppress joint inflammation and preserve functional capacity but true disease modification has yet to be shown. The toxicity associated with presently available immunomodulatory agents makes careful patient selection and conscientious monitoring essential. The efficacy of methotrexate and sulfasalazine in patients with psoriatic arthritis is well defined while more anecdotal reports of benefit exist for other agents including the antimalarials, azathioprine, colchicine, cyclosporine, and the retinoids. For all treatment regimens, the magnitude of clinical improvement demonstrated to date has been rather small and quite subjective in character with few controlled studies of adequate size and duration having been reported. Emerging biologic therapies, such as those which target tumor necrosis factor, will hopefully provide future treatment options with greater efficacy and improved safety for patients with psoriatic arthritis. PMID- 11770392 TI - Relationship between systemic corticosteroids and osteonecrosis. AB - Numerous reports describe osteonecrosis after oral corticosteroid therapy. It is still uncertain if corticosteroid treatment alone or in combination with other factors leads to the development of this condition. The literature presents controversial clinical and experimental data. The most affected site for osteonecrosis is the femoral head and therefore our considerations are concentrated at this site. Oral corticosteroids are commonly used in dermatology, especially in the treatment of connective tissue diseases and hypersensitive diseases. This clinical review evaluates the relationship between and the onset of femoral head necrosis. Although osteonecrosis of the femoral head can be caused by various conditions such as trauma, excess alcohol and hemoglobinopathies, studies indicate that treatment with corticosteroids is the most common cause of the condition. There is some controversy on the role of underlying disease and total corticosteroid dose administered, in the development of osteonecrosis of the femoral head. MRI scans are used to establish an early diagnosis. There are several surgical and nonsurgical options for disease management, dependent on the stage of disease, the age of the patient and other risk factors. In general, the risk for osteonecrosis is considered to be low under oral corticosteroid therapy. So far, no data can establish a direct relationship, but data still strongly suggest an existing cause and effect relationship. Further investigations are necessary for example, a large controlled prospective long-term study, to further refine an association between the corticosteroid dose, the duration of treatment and other risk factors. Dermatologists who prescribe oral corticosteroids, should always be aware of the potential risk of avascular femoral head necrosis and the patients should be informed about this severe complication of oral coricosteroid therapy. PMID- 11770393 TI - Tacrolimus ointment. A review of its therapeutic potential as a topical therapy in atopic dermatitis. AB - Tacrolimus, a macrolide immunomodulator, is believed to control atopic dermatitis by inhibiting T lymphocyte activation, altering cell surface expression on antigen-presenting dendritic cells and modulating the release of inflammatory mediators from skin mast cells and basophils. Tacrolimus ointment penetrates human skin with no systemic accumulation after repeated applications; systemic absorption is generally low, with most patients in clinical trials having blood concentrations of the drug below the limit of quantification. Moderate to severe atopic dermatitis significantly improved (measured using multiple end-points, including > or = 90% improvement in Physician's Global Evaluation of Clinical Response) with tacrolimus 0.03 and 0.1% ointment compared with vehicle in both adult (n = 304 and 328) and pediatric (n = 351) patients in three 12-week, double blind, randomized, phase III trials. In adults, tacrolimus ointment was effective therapy for the treatment of atopic dermatitis on all skin regions, including the head and neck. The 0.1% concentration was more effective than the 0.03% concentration. Clinical improvement in moderate to severe atopic dermatitis in adult (n = 316) or pediatric (n = 255) patients was seen as early as week 1, and improvement continued and/or was maintained for up to 6 and/or 12 months in long term studies. The 0.1% formulation was also effective and well tolerated for up to 2 years. Tacrolimus 0.03 and 0.1% ointment was associated with significant quality-of-life benefit in adults, children (aged 5 to 15 years) and toddlers (aged 2 to 4 years) with atopic dermatitis in 12-week phase III trials (n = 985). Skin burning and pruritus were the most common application site adverse events in adult and pediatric patients in short-term and long-term trials. These events were generally of short duration and mild or moderate severity. Cutaneous infections occurred with a similar incidence after treatment with tacrolimus ointment to that seen after vehicle in short-term trials. CONCLUSION: Both short- and long-term monotherapy with tacrolimus 0.03 and 0.1% ointment improves moderate to severe atopic dermatitis in adult and pediatric patients. Topical tacrolimus ointment is well tolerated, with the majority of adverse events being localized, transient in nature and of mild or moderate severity. Tacrolimus ointment provides a promising addition to the currently available treatments for atopic dermatitis; it can be used as a short- or long-term intermittent therapy for moderate to severe disease, including disease on the head or neck, in adult (0.1 and 0.03% formulations) and pediatric (0.03% formulation) patients who are not adequately responsive to or are intolerant of conventional treatments. PMID- 11770394 TI - Cutaneous drug reaction case reports. From the world literature. AB - Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International, Auckland, New Zealand) and Medline. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage). PMID- 11770395 TI - [Cataract visual recuperation project in the 21st century and its challenges]. PMID- 11770396 TI - [Analysis, prospect and treatment of causes of phacoemulsification complications]. AB - OBJECTIVE: To analyse the causes of different complications of phacoemulsification and to investigate their principles of treatment and prevention. METHOD: The causes of different complications in 187 (180 cases) of 2,250 eyes having undergone phacoemulsification were analyzed. RESULTS: Intraoperatively, the common complications of phacoemulsification were posterior capsular rupture in 70 eyes (3.1%), iris damage in 16 eyes (0.7%), iris prolapse in 6 eyes (0.3%), drop of lens fragments into vitreous in 3 eyes (0.1%) and tear of Descernent's membrane in 4 eyes (0.2%). The common complications after the operation were corneal endothelial edema in 89 eyes (4.0%), corneal decompensation in 2 eyes (0.1%), temporary intraocular hypertension in 28 eyes (1.2%), pupillary dilatation in 7 eyes (0.3%), retinal detachment in 8 eyes (0.4%), cystoid macular edema in 24 eyes (1.1%) and displacement of intraocular lens in 8 eyes (0.4%). CONCLUSIONS: The different complications can be diminished following the popularization and development of phacoemulsification. It should be properly managed once the complication has occurred, and good operative effects can be obtained. PMID- 11770397 TI - [Refraction shift after intraocular lens implantation in children]. AB - OBJECTIVE: To evaluate the refraction shift after posterior chamber intraocular lens (PC-IOL) implantation in children. METHODS: A long term retrospective study involved 65 eyes of 65 patients aged from 5 to 12 years who underwent PC-IOL implantation between December 1988 and December 1994. The mean follow-up was 7.1 years (range 5 to 10 years). Refraction shift, keratometric readings and axial length were periodically measured. Sixty-five healthy eyes were in the control group. RESULTS: The mean preoperative axial length of the surgical group was (22.48 +/- 0.44) mm, and of the control group, (22.43 +/- 0.41) mm. There was no statistically significant difference in axial length after 10 years in both groups, (23.45 +/- 0.53) mm in surgical group and (23.41 +/- 0.50) mm in control group. All the eyes showed a myopic drift with 3.29 D in surgical group and 1.75 D in control group (F = 2.318, P < 0.05). CONCLUSION: The ocular growth of children is found to be unaffected by the PC-IOL implantation, the choice of IOL power should be retained in physiological hyperopia in pseudophakic children. PMID- 11770398 TI - [Phacoemulsification and intraocular lens implantation in patients with chronic renal failure and cataract]. AB - OBJECTIVE: To report the experience in treatment of phacoemulsification and intraocular lens implantation and to evaluate its efficacy in patients with chronic renal failure and cataract. METHODS: Twelve patients with chronic renal failure, maintenance dialysis and cataract were treated with phacoemulsification and intraocular lens implantation in 1998-1999. The original disease of renal failure was non-diabetic. The average age was 51 years, and the average time course on dialysis was 6-12 months. All the patients were stable on maintenance dialysis, and the blood pressure was controlled in or near normal range. Before the operation, the administration of heparin was stopped, and the hemostatic drug was applied. RESULTS: All the procedures were performed on 23 eyes these patients without any complications. The naked visual acuity after operation improved significantly in comparison with that before the operation. At the postoperative one month of follow-up, the visual acuity of 52% of the surgical eyes was above 1.0. CONCLUSION: Phacoemulsification and intraocular lens implantation is effective and safe in chronic renal failure patients with cataract. PMID- 11770399 TI - [Comparison between one-site and two-site incision in phacotrabeculectomy]. AB - OBJECTIVE: To compare the effect of one-site and two-site incision in phacotrabeculectomy in terms of intraocular pressure control. METHODS: Forty-five cases (47 eyes) of phacotrabeculectomy were retrospectively reviewed. The nuclei of all the cases were not harder than Grade III. One-site approach was performed on 29 eyes, and two-site approach, on 18 eyes. The effects of intraocular pressure control were compared between the two groups. RESULTS: Follow-up was 13 30 months (mean 18.9 months). The postoperative intraocular pressure in the one site group was (16.81 +/- 4.56) mm Hg (1 mm Hg = 0.133 kPa), (15.32 +/- 6.67) mm Hg lower than that before surgery. And the postoperative intraocular pressure in the two-site group was (17.63 +/- 4.60) mm Hg, (16.42 +/- 6.98) mm Hg lower than that before surgery. There was no significant difference between the two groups relative to the effect of intraocular pressure control (t = 1.44, P > 0.05). CONCLUSION: Phacotrabeculectomy, either with one-site approach or with two-site approach, can provide good intraocular pressure control. The effects are similar between the two approaches in soft cataract patients. PMID- 11770400 TI - [The therapeutic effects and postoperative complications of cataract surgery in Laiwu City]. AB - OBJECTIVE: To decrease the prevalence of blindness and low vision in Laiwu City. METHODS: The therapeutic effects and postoperative complications of each method of cataract surgery were investigated and statistically analyzed. The cases with postoperative complications were treated after surgery. RESULTS: In the investigation, 1,274 eyes of 1,089 cases had undergone cataract surgeries, including couching for cataract, intracapsular cataract extraction (ICCE), extracapsular cataract extraction (ECCE) and ECCE with intraocular lens implantation. The prevalence of blindness and low vision was 4.87% and 23.70%, respectively. There were postoperative complications in 650 eyes (51.02%). They were corneal decompensation, secondary glaucoma, opacity of posterior capsuler, cystoid macular edema and retinal detachment. After treatment for the postoperative complications, the prevalence of blindness and low vision was decreased to 1.96% and 6.01%, respectively. The cases having escaped the blindness and handicap after treatment were lowest in the groups of couching and ICCE. CONCLUSIONS: The survey on the population having undergone cataract surgery in rural district is important. The postoperative complications can be treated in time and the prevalence of blindness and low vision can be decreased. PMID- 11770401 TI - [Expression of vimentin in lens epithelial cells of age-related cataract]. AB - OBJECTIVE: To observe the expression of vimentin in the lens epithelial cells and superficial cortex of age-related cataract. METHODS: Twenty-six paraformaldehyde fixed flat preparations of human lens epithelium attached to the anterior capsule and obtained during extracapsular cataract extraction were studied. Of these, 22 were studied and compared to the 10 samples from normal lenses with antibody to vimentin by avidinbiotinylated peroxidase complex (ABC) method and observed with a light microscope, and 6 (4 cataractous and 2 normal) were used for pre embedding immunoelectron microscopy. Vimentin in superficial layers (epithelium and superficial cortex) of 4 cataractous lenses were analysed by SDS polyacrylamide gel electrophoresis (PAGE) and Western blot method. RESULTS: The average gray level values for expression of vimentin were 143.84 +/- 8.52 and 134.87 +/- 14.27 in cataract and normal group, respectively (t = 2.0948, P < 0.05). Ultrastructure of epithelial cells showed a decrease of intermediate filaments, accumulation of vimentin in bundle and organelle degeneration. Vimentin was identified in the superficial layers of normal and immature cataractous lenses by SDS-PAGE and Western blot. In another two mature cataractous lenses, little vimentin was detected. CONCLUSION: Decrease of vimentin may be initiated by damage to the epithelial cells leading to degradation of cytoskeleton, and appears to be related with the formation of age related cataract. PMID- 11770402 TI - [A clinical analysis of 112 cases with glucocorticoid glaucoma]. AB - OBJECTIVE: To investigate the etiology, clinical characteristics, treatment and prevention of glucocorticoid glaucoma (GIG). METHODS: Retrospectively, 112 cases (215 eyes) with GIG including 79 males and 33 females in the age range 6-69 years were studied. RESULTS: One hundred and ten cases used glucocorticoid locally, 2 cases used it systemically, and the mean therapeutic time was (27.5 +/- 23.18) months. Conjunctivitis of various causes was the main disease to use glucocorticoid, all 215 eyes had the defect of visual field caused by hypertension, damage of optic disc and retinal nerve fiber layers, just like primary open-angle glaucoma. The degree of injury was related to the therapeutic time. The IOP was decreased after the use of glucocorticoid was stopped, but it could not get to the normal level. There were 162 eyes (75.4%) with characteristic posterior subcapsular cataract and 76 cases combined with myopia. CONCLUSION: The important cause leading to GIG is the abuse of glucocorticoid. The history of using glucocorticoid and the posterior subcapsular cataract are the main bases in the diagnosis and differential diagnosis of GIG. PMID- 11770403 TI - [Clear lens extraction with phacoemulsification and posterior chamber intraocular lens implantation for treatment of high myopia]. AB - OBJECTIVE: To probe into the effectiveness and safety of clear lens extraction with phacoemulsification and implantation of posterior chamber intraocular lens (PC-IOL) to correct high myopia. METHODS: Phacoemulsification and implantation of PC-IOL through scleral tunnel incision was performed on 36 eyes of 26 high myopic patients with clear crystalline lens. The average age of patients was 53.9 years (36-67 years) old. The preoperative corrected visual acuity was 0.2-1.0. The mean preoperative spherical equivalent and astigmatism was (-13.11 +/- 4.33) D and (0.72 +/- 0.91) D respectively. The mean axial length was (28.02 +/- 2.14) mm. The mean diopter of IOL was (+8.62 +/- 4.76) D. RESULTS: The uncorrected visual acuity improved in all cases postoperatively, with 25 eyes (69.4%) achieving > or = 0.5. After surgery, the corrected visual acuity improved in 27 eyes (75.0%), and was > or = 0.5 in 35 eyes (97.2%). The mean postoperative spherical equivalent and astigmatism was (-1.51 +/- 0.60) D and (0.64 +/- 0.80) D respectively. The average follow-up was 23.5 months (7-35 months). The postoperative complication was posterior capsular opacification (5.6%). No retinal hole or detachment and cystoid macular edema were observed in this series. CONCLUSIONS: Clear lens phacoemulsification and PC-IOL implantation to correct high myopia is a safe, effective procedure serving as a refractive surgery. It is worth to spread due to good outcome of visual acuity, low incidence of complications, high predictability and stability. PMID- 11770404 TI - [Preliminary clinical study on the management of angle-closure glaucoma by phacoemulsification with foldable posterior chamber intraocular lens implantation]. AB - OBJECTIVE: To investigate the clinical results of phacoemulsification with foldable posterior chamber intraocular lens (PC-IOL) implantation in the management of angle-closure glaucoma with cataract. METHODS: Phacoemulsification with PC-IOL implantation performed on 47 eyes (42 cases) with angle-closure glaucoma and cataract was retrospectively studied, including 26 eyes with primary acute angle-closure glaucoma, 12 eyes with primary chronic angle-closure glaucoma, 5 eyes with secondary acute angle-closure glaucoma and 4 eyes with secondary chronic angle-closure glaucoma. RESULTS: After a mean postoperative follow-up of (18.40 +/- 9.51) months, the intraocular pressure was reduced from a preoperative mean of (25.47 +/- 18.43) mm Hg to a postoperative mean of (11.99 +/ 4.48) mm Hg (t = 4.918, P < 0.001). The mean anterior chamber depth was (1.69 +/ 0.46) mm preoperatively and (2.28 +/- 0.36) mm postoperatively (t = 7.738, P < 0.001). The best-corrected visual acuity was improved in 41 of 47 eyes (87.2%). CONCLUSION: Phacoemulsification with posterior chamber foldable intraocular lens implantation can be a good alternative in treating angle-closure glaucoma with cataract. PMID- 11770405 TI - [A study on the treatment of secondary glaucoma due to intumescent senile cataract]. AB - OBJECTIVE: To discuss surgical methods of treating secondary glaucoma due to intumescent senile cataract. METHODS: Of 47 inpatient cases (49 eyes) who suffered from secondary glaucoma due to intumescent senile cataract, 28 cases (30 eyes) had been performed the following four different types of operation; (1) extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC-IOL) implantation with peripheral iridectomy, (2) ECCE and PC-IOL implantation with segmental iridectomy, (3) ECCE and PC-IOL implantation with trabeculectomy, and (4) five-combined-operation including scleral trephination, cyclodialysis, vitreous paracentesis, ECCE and PC-IOL implantation. RESULTS: The corrected visual acuities in 28 eyes had improved, whereas that in 2 eyes did not improve because of optic nerve atrophy. All the intraocular pressure in 30 eyes was within normal limit, including 12 eyes topically using antiglaucoma drugs. CONCLUSION: Most of patients with secondary glaucoma due to intumescent senile cataract can be cured surgically by iridectomy or trabeculectomy combined with ECCE and PC-IOL implantation. The five-combined-operation is an effective way to treat difficult cases such as long-term disease course, result with antiglaucoma drugs not satisfactory and swelling lens with flat anterior chamber. PMID- 11770406 TI - [Treatment of congenital jerky nystagmus with opposite bidirectional neutral zone]. AB - OBJECTIVE: To explore a method for the treatment of congenital jerky nystagmus with opposite bidirectional neutral zones. METHOD: The relatively used side between the two neutral zone was found by neutralizing bilateral head torsion angle with prisms. The surgical intervention was indicated for those patients whose head position would not turn to another side. RESULT: There were 14 cases treated by this method, none of these cases whose head position turned to another side. Ten cases underwent once operation, 2 cases, twice operations and another 2 cases undertook once operation with additional prism correction. The compensatory head posture was corrected and the vision in the primary position of gaze was improved in all the cases. CONCLUSION: This therapy for congenital jerky nystagmus with opposite bidirectional neutral zone shows significant therapeutic effects and can be available for clinical application. PMID- 11770407 TI - [Quantitative analysis of early influence on anterior ocular segment of diabetic retinopathy by retinal photocoagulation]. AB - OBJECTIVE: To investigate early influence on anterior ocular segment of diabetic retinopathy (DR) by retinal photocoagulation. METHODS: Ultrasound biomicroscopy (UBM) was applied to obtain and analyze quantitatively the changes of anterior ocular segment, including the anterior chamber, anterior chamber angle, ciliary body and choroid before the retinal photocoagulation and on the 3rd and 7th day after the therapy in 36 eyes with DR. RESULTS: Significant elevating of intraocular pressure (IOP), narrowing of chamber angle and slight shallowing of anterior chamber were observed on the 3rd day after retinal photocoagulation. Ciliary detachment and choroidal detachment were observed simultaneously in 29 eyes (80.6%). Ciliary detachment or choroidal detachment occurred singly in 3 eyes (8.3%) on the 3rd day and most of them disappeared on the 7th day spontaneously The height of ciliochoroidal detachment in the superior quadrant is greater than that in other quadrants. The severity of ciliochoroidal detachment is negatively correlated to the age, not correlated to fast blood sugar, duration of diabetes and duration of DR. CONCLUSION: Temporary ciliochoroidal detachment with changes of anterior chamber angle and IOP may be a common complication after retinal photocoagulation that should be designed properly. PMID- 11770408 TI - [A study of Humphrey three zone screening to detect visual field of the patients with pituitary macroadenomas]. AB - OBJECTIVE: To evaluate the clinical application of Humphrey three zone screening in detecting the visual field of the patients with pituitary macroadenomas (PMA). METHODS: There were two groups in the study. The PMA group: 128 PMA cases were selected who had symptoms of visual problem and been diagnosed with computer tomography (CT) or magnetic resonance (MR) and without apparent opacity of refractive medium. The low myopia group: thirty cases with low myopia and without other eye diseases were included. Humphrey three zone screening method was used to detect the 76-points in the central 30 degree visual fields of the patients of the two groups. RESULTS: In PMA group, 99.2% of the 128 patients and 87.1% of their eyes had visual field defect. 86.7% of the patients had the visual field defect mainly located at the temporal side and showed or tended to have a medial vertical limit. In detecting abnormality of the patients, three zone screening test had a sensitivity of 99.2% (percent of cases with true visual field defect identified by the field test). The mean test duration of each eye is (5.8 +/- 2.2) minutes. In low myopia group, two eyes of two patients had visual field defect. In testing the normal group, three zone screening test had a specificity of 93.3% (percent of cases without true visual field defect appropriately identified by the field test). CONCLUSION: Humphrey three zone screening has very high sensitivity and specificity in detecting visual field, and it is simple, fast and practical for detecting the visual field of the patients with PMA. It plays an important role in implying diagnosis and avoiding misdiagnosis of PMA. PMID- 11770409 TI - [Relationship between ocular axial length and central retinal vein occlusion]. AB - OBJECTIVE: To evaluate the relationship between ocular axial length and central retinal vein occlusion (CRVO). METHODS: A-scan ultrasonography was used to measure the ocular axial length in 30 patients with CRVO (the CRVO group) and 30 normal persons and 90 patients with cataract matched in sex and age with the former group (the control group). RESULTS: The mean axial length of the affected eyes in CRVO group was (22.54 +/- 0.74) mm, and that of the follow eyes, (22.95 +/- 0.92) mm. The mean axial length of the affected and the fellow eyes in CRVO group did not differ statistically (t = 2.94, P > 0.05). The mean axial length in the right eyes of the control group was (23.45 +/- 0.66) mm and that of the left eyes, (23.56 +/- 0.95) mm, the difference being not significant statistically (t = 1.96, P > 0.05). The difference in axial length between the eyes with CRVO and the eyes in the control group was statistically significant (t = 4.09, P < 0.01). CONCLUSION: Short axial length is one of the risk factor for central retinal vein occlusion. PMID- 11770410 TI - [Accidental perforation of the globe during peribulbar injection]. AB - OBJECTIVE: To evaluate clinical manifestations, management, visual outcome and prevention of accidental penetration of the globe during peribulbar injection. METHODS: The medical records of 12 cases were retrospectively reviewed. The disposable needle was used in all the cases except one to whom a reusable needle was applied. Lidocaine was injected in 2 cases, steroid or steroid combined with antibiotics was injected in the remaining ones. RESULTS: The main symptoms were acute loss of visual acuity (VA) and pain in the involved eye. The signs included vitreous hemorrhage, white steroid material in the vitreous cavity, retinal break and detachment, high intraocular pressure or hypotony and rupture of cataract surgical wound. The treatments consisted of vitrectomy, the repair of retinal detachment or ruptured cataract surgical wound. Six cases ended with VA < or = 0.05. CONCLUSION: Inadvertent intraocular perforation during peribulbar injection is a serious complication. The best method to rescue such cases is prevention. PMID- 11770411 TI - [Presynaptic 5-hydroxytryptamine receptors enhance cholinergic neurosecretion in the human iris-ciliary body]. AB - OBJECTIVE: To characterize presynaptic 5-hydroxytryptamine (5-HT) heteroreceptors which modulate 3H-acetylcholine (3H-ACh) release in isolated human iris-ciliary bodies (ICBs). METHODS: ICB tissue segments were perfused and incubated with 3H choline, and electrically stimulated four times (S1, S2, S3 and S4) at 10 Hz for 1 min to elicit 3H-ACh secretion. Test agents, 5-HT agonists and antagonists, were added before S2, S3 and S4 and their effects were determined by the stimulation ratio (Sx/S1) of evoked 3H-ACh release. 3H-ACh in perfusate fractions was isolated by ion exchange chromatography and analyzed for radioactivity by liquid scintillation spectrometry. RESULTS: The evoked 3H-ACh release was enhanced in a concentration-dependent manner by 5-HT [10(-9)-10(-5) mol/L, 50% effective concentration values (EC50) = 3.36 x 10(-8) mol/L] as well as 5 methoaxytryptamine [5-MOT (agonist), 10(-8)-10(-5) mol/L, EC50 = 6.59 x 10(-7) mol/L]. The selective 5-HT4 antagonist, GR113808A (10(-8) mol/L) inhibited the 5 HT-inducing increase of the cholinergic response, producing parallel right shifts of the 5-HT concentration-response curves (t = 4.012, P < 0.01). The selective 5 HT3 antagonist ondersetron (5 x 10(-7) mol/L) and tropisetron (10(-9) mol/L) did not affect 5-HT inducing 3H-Ach release (t = 2.215, P > 0.05). CONCLUSION: Our results indicate that cholinergic terminals in the human ICB contain 5-HT heteroreceptors that may promote the release of 5-HT and belong to the 5-HT4 subtype. PMID- 11770412 TI - [Expression of nitric oxide synthase-2 in specific cells of human glaucomatous optic nerve head]. AB - OBJECTIVE: To investigate the specific cells expressing nitric oxide synthase-2 (NOS-2) in the optic nerve head of patients with primary open angle glaucoma. METHODS: Double-labeling immunohistochemistry was used for labeling of NOS-2 and one of the specific cell markers. RESULTS: NOS-2 was labeled in the astrocytes. The NOS-2 positive astrocytes were mainly located in the damaged area of nerve fibers. A few arteries had NOS-2 labeling in the endothelial cells. There was no significant labeling of NOS-2 in microglia, vascular smooth muscle cells and pericytes. CONCLUSION: In glaucomatous optic nerve neuropathy, NOS-2 is mainly expressed by astrocytes. Astrocytes may play an important role in the local neurotoxicity of axons of the ganglion cells by producing excessive nitric oxide. PMID- 11770413 TI - [An investigation on morphology of experimental corneal neovascularization]. AB - OBJECTIVE: To observe the morphologic character of the corneal neovascularization in experimental rabbits and also compare it with the morphology of that after irradiation with beta-rays. METHODS: A model of new blood vessels on the corneas of New Zealand rabbits was established with silver nitrate burning. The growth character of the neovascularization was compared between the irradiated and non irradiated groups. The casting of the new blood vessels in different periods was made and the morphologic differences between the two groups were compared under a scanning electron microscope. RESULTS: The corneal new blood vessels occurred and continuously proliferated with the typical method of budding. The formation of buds was obviously inhibited and damaged after irradiation with  or  beta-rays, and the irradiated new branches were also atrophic and necrotic. CONCLUSIONS: Stopping the budding procedure of the corneal neovascularization may inhibit the formation and development of the corneal new blood vessels. PMID- 11770414 TI - [A study of the effects of basic fibroblast growth factor on fibrovascular ingrowth into hydroxyapatite orbital implants]. AB - OBJECTIVE: To investigate the effects of different doses of basic fibroblast growth factor (bFGF) on the fibrovascular ingrowth into hydroxyapatite orbital implants. METHODS: Thirty-six New Zealand albino rabbits were divided into 4 groups, and hydroxyapatite orbital spheres were implanted into their orbits. The implants were pretreated with 0.5, 1.5 and 5.0 g/L bFGF solution respectively in 3 groups, the untreated implants were used in the control group. At the postoperative 2, 4 and 6 weeks the implants were harvested. Observers classified the extent of the fibrovascular ingrowth in a blind manner under light microscopy. RESULTS: Histologic studies demonstrated that postoperatively, the rate of vascularization of the implants pretreated with 1.5 and 5.0 g/L bFGF solution was significantly increased at week 2 in comparison with that of the control group. No difference was noted between the group with the implants pretreated with 0.5 g/L bFGF solution and the control group. CONCLUSION: The bFGF 1.5 and 5.0 g/L in concentration may promote the fibrovascular ingrowth into hydroxyapatite orbital implants at week 2 after the implantation. PMID- 11770415 TI - [Two points concerning the prevention and management of chronic obstructive pulmonary diseases]. PMID- 11770416 TI - [Results of community intervention trial for chronic obstructive pulmonary diseases and chronic cor-pulmonale from 1992 to 1999]. AB - OBJECTIVE: To evaluate the effect of community intervention for COPD and chronic cor-pulmonale. METHODS: The baseline survey of the study was carried out in 1992. The total population was randomly divided into intervention and control regions. From 1992 the comprehensive community intervention trial was conducted in the intervention region. The data of baseline study has been published elsewhere. The family inquiry was made in all baseline population, 50 percent of high risk population and 100 percent of COPD and cor pulmonale population were reexamined. RESULTS: Of the 3,739 subjects who should be investigated 3,316 subjects were really investigated (88.7% of responsive rate). Of 814 subjects randomly abstracted from 3,316 in intervention and control regions, the awareness rates of smoking harm to health were 95.0% and 80.0%, of how to prevent and treat COPD were 62.0% and 35.7%, of regular visit by doctors were 46.1% and 27.0% respectively. The rate of ex-smoker was 28.2% in intervention region more than that of 23% in control region (P = 0.004). Of 3,075 subjects undergone lung function test, FEV1 decrements per capita yearly were 32.0 ml and 37.9 ml (P = 0.001); FVC decrement were 42.0 ml and 48.3 ml (P = 0.012) in intervention and control regions. The prevalence increment in COPD were 5.6% and 8.0% (P = 0.03), cor-pulmonale were 3.5% and 6.7% (P = 0.02) compared to baseline survey in both regions. The mortality of cor-pulmonale were 72.9 and 95 per 100,000 per year (P = 0.0044) from 1995 to 1999. CONCLUSION: The rate of quiting smoke is significantly increased by intervention. The declination of lung function significantly decreases. The increment in prevalence of COPD and cor-pulmonale significantly decreases. The mortality of cor-pulmonale decreases significantly in intervention region. The results indicates that the comprehensive intervention in community is an important measurement for decreasing incidence of COPD and mortality of cor-pulmonale. PMID- 11770417 TI - [The relationship between bronchial hyperresponsiveness and chronic obstructive pulmonary disease]. AB - OBJECTIVE: To explore the relationship between bronchial hyperresponsiveness and chronic obstructive pulmonary disease (COPD). METHODS: 154 smokers with COPD (FEV1/FVC < 70%) served as a study group and 154 smokers without COPD as a control group and 23 never-smokers as a healthy control group from 23 villages in Fangshan Distract, Beijing in June, 1996. The patients with self-reported and doctor-diagnosed asthma were excluded from participants. Those subjects were divided into a positive group and a negative group based on methacholine bronchial responsiveness. All subjects were worked up in May, 2000. RESULTS: (1) Baseline case-control study: The positive rate of bronchial hyperresponsiveness was 78% in the study group, PC20 = (1.4 +/- 1.6) g/L; however 28% of the matched group were positive, PC20 = (2.7 +/- 2.3) g/L, (P < 0.001); (2) Prospective study: Of 154 pairs case-controls 241 subjects were followed up in May 2000. The rate of following up was 78.2%. The incidence of COPD was 23.7% in 38 subjects without COPD with positive hyperresponsiveness, however incidence of COPD was 9.5% in 84 subjects without COPD with negative hyperresponsiveness (P = 0.036), the relative risk (RR) = 2.5. The rate of FEV1/FVC > or = 70% was 12.9% in 93 patients with COPD and positive hyperresponsiveness, however it was 30.8% in 26 patients with COPD and negative hyperresponsiveness (P = 0.031). CONCLUSION: In smoking population, the bronchial hyperresponsiveness lead to more chronic obstructive pulmonary disease and it may be one of the susceptible risk factors for COPD. PMID- 11770418 TI - [A study of the effect of protein kinase C on the expression of nitric oxide synthase mRNA in pulmonary artery smooth muscle in hypoxia]. AB - OBJECTIVE: To investigate the effect of PKC on the expression of NOS mRNA in pulmonary artery smooth muscle cell(PASMC) in hypoxia. METHODS: RT-PCR was used to detect the expression of PKC alpha mRNA in PASMC of procine, and the effect of activator and inhibitor of PKC on the expression of cNOS mRNA in PASMC. RESULTS: The expression of PKC-alpha mRNA was higher in the PASMC in 48 and 72 h of hypoxia(P < 0.01), and the expression of cNOS mRNA was lower(P < 0.01). The expression of cNOS mRNA was significantly negatively correlated with the expression of PKC-alpha mRNA(P < 0.001). PMA, an agonist of PKC could reduce the expression of cNOS mNRA in hypoxia, while RO 31-8220, an inhibitor of PKC could inhibit it and enhance the expression of NOS mRNA(P < 0.01). The activator of NO, L-Arg and inhibitor, L-NAME had no effect on expression of PKC-alpha mRNA. CONCLUSION: The PKC can inhibit the expression of cNOS mRNA in PASMC in hypoxia. The effect of PKC in hypoxic pulmonary hypertension may be made by inhibiting the expression of cNOS mRNA and modulating NO. The site of the effect of PKC may be in upstream of NO. The mechanism of it needs to be studied further. PMID- 11770419 TI - [Establishment and experimental study on mouse model of Chlamydia pneumoniae pneumonitis]. AB - OBJECTIVE: To evaluate mice as experimental animals for Chlamydia pneumoniae (C. Pneumoniae) infection and investigate the pathogenesis of C. pneumoniae pneumonitis. METHODS: The Icr mice were inoculated with C. pneumoniae, strain CWL 029, by the intranasal or intravenous routes. After a single inoculation, mice were killed on the 1st, 3rd, 7th, 15th, 21th, 28th and 60th day separately. The pathological changes of lung tissue were analyzed. RESULTS: The Icr mice were shown to be susceptible to C. pneumoniae. Inoculation of mice with C. pneumoniae induced a prolonged course of lung infection, as demonstrated by persistence of lung pathology (60 days). In the intranasal inoculation of mice, the lung pathology was characterized by patchy interstitial pneumonitis with predominately neutrophil leukocyte infiltration in the early(7 days) and lyphocytes infiltration in the later stages(14 days later) of infection. After i.v. inoculation, a similarly interstitial pneumonitis was seen, but it was milder and more patchy, especially in the early stage. C. pneumoniae DNA was detected by polymerase chain reaction(PCR) intermittently in the lung tissue. Inoculated mice developed serum IgG antibody responses. CONCLUSIONS: The Icr mice were shown to be susceptible to C. pneumoniae and the pulmonary infection was characterized by interstitial pneumonitis, especially in mice of intranasal inoculation. PMID- 11770420 TI - [Study of pefloxacin concentration in blood and sputum in the aged pneumonia patients with impairment of renal function]. AB - OBJECTIVE: To study the drug concentration in blood and sputum, clinical effect and drug toxicity of pefloxacin in the aged pneumonia patients with different degree of impairment of renal function. METHODS: The patients were divided into four groups according to the impairment of renal functions pefloxacin 400 mg/12 h venous inflow, period of treatment is 10 days. Clinical manifestation and experimental index were registered; the drug concentration in blood and sputum was measured with biochemical technique, then compared and analyzed. RESULTS: The drug concentration in blood and sputum in four groups differed from the degree of the impairment of renal function. The concentration of drug in blood and sputum of the normal renal function was close to that in the low-grade impairment of renal function. Their clinical effective ratios were 83%, 80%, bacterium cleanup ratio was 86%. The difference of drug concentration in blood and sputum in the severe impairment of renal function was greater than that in the moderate renal function group, their clinical effective ratios were 66%, 53%, bacterial cleanup ratios were 57%, 36%, adverse reaction was growing along with degree of impairment of renal function. This drug has renal toxicity for moderate and severe impairment of renal function. CONCLUSION: In case of moderate impairment of renal function, prolongation of dose interval should be considered; pefloxacin should be avoided in severe impairment of renal function. PMID- 11770421 TI - [The research of pancadherin and beta-catenin expression in pulmonary tissue of mice with bleomycin-induced pulmonary fibrosis]. AB - OBJECTIVE: To investigate the changes of pancadherin(Pan-cd) and beta catenin(beta-cat) expression in pulmonary tissue of mice with bleomycin (BLM) induced pulmonary injury and explore the relation between the Pan-cd/beta-cat expression and pulmonary fibrosis. METHOD: A single dose of BLM was intratracheally injected to induce pulmonary fibrosis of mice. Animals were killed and immunohistochemical methods were used with polyclonal anti-Pan-cd and anti-beta-cat antiserum. RESULTS: The expression of Pan-cd in type I alveolar cells was down-regulation. The expression of Pan-cd in type II alveolar cells was induced. The expression of Pan-cd and beta-cat in small airway epithelial cells were all down-regulation and were repeated with the way of down-regulation reparation-down-regulation. The expression of Pan-cd on membrane in small airway epithelial cells decreased, whereas the cytoplasmic expression increased and was repeatedly alternated between cytoplasma with membrane. The expression of Pan-cd in alveolar macrophage and interstitial cells increased. CONCLUSION: The abnormal expression of cadherin and beta-cat may play a role in the pathogenesis of pulmonary fibrosis after pulmonary injury. PMID- 11770422 TI - [Changes of pulmonary function and partial oxygen pressure before and after bronchoalveolar lavage in patients with interstitial lung diseases]. AB - OBJECTIVE: To study the influence of bronchoalveolar lavage(BAL) on pulmonary physiological function and partial oxygen pressure(PaO2). METHODS: Pulmonary function and partial oxygen pressure were measured in 42 patients with interstitial lung disease (ILD) before and after BAL, 7 non-smoker volunteers as control group. RESULTS: VC% and FEV1% decreased significantly from (74 +/- 17)% to (64 +/- 19)% and from (72 +/- 9)% to (65 +/- 12)%, respectively. PaO2 decreased from(77 +/- 11) mm Hg to (63 +/- 11) mm Hg. The above parameters were also decreased in control group, but had no statistical significance. CONCLUSION: Pulmonary physiological function and partial oxygen pressure of patients with ILD are influenced by BAL process. PMID- 11770423 TI - [Quantitative studies on expression of peripheral blood CD44 and CD54 in non small cell lung carcinoma]. AB - OBJECTIVE: To assess the relationship between expression of peripheral blood CD44 and CD54 in lymphocyte with non-small cell lung cancer and clinicopathological features. METHODS: Peripheral blood CD44 contents in 50 patients with lung cancer were detected by flow-cytometry, 30 normal donors and 25 patients with benign lesions served as controls. RESULTS: Peripheral blood CD44 and CD54 in lymphocyte with lung cancer were significantly higher than those in benign lesions and normal controls (P < 0.01). There is no distinct difference between CD44 and CD54 in benign lesions and normal controls (P > 0.05). Lung cancer with lymph node metastasis showed higher expression of CD44 and CD54 than lung cancer without lymph node metastasis (P < 0.01). Distinctly statistic difference was showed between CD44 in stage III, IV and stage I, II (P < 0.01). CD54 content in stage IV was higher than that in stage I, II and III, respectively. Histopathological grade was significantly associated with the expression of CD44 and CD54. Peripheral blood CD44 and CD54 contents were not related with squamous cell carcinoma and adenocarcinoma. CONCLUSION: Detection of CD44 and CD54 levels by flow cytometry might be used as a marker to evaluate prognosis and metastasis in patients with non-small cell lung cancer. PMID- 11770425 TI - [Application of rapid detection for Mycobacterium tuberculosis with phage splitting assay]. AB - OBJECTIVE: To study the significance of rapid identification for Mycobacterium tuberculosis with phage splitting assay. METHODS: Strains of Mycobacterium tuberculosis, non-tuberculosis mycobacterium, non-mycobacterium and samples of sputum with pulmonary tuberculosis were rapidly detected by phage spot technique. RESULTS: The strains of Mycobacterium tuberculosis H37Rv, bovis and africanum were all positive. The results of 10 strains of non-tuberculosis mycobacterium and 7 strains of non-mycobacterium were negative. All of 30 clinical isolates from the patients of the pulmonary tuberculosis were positive. 19 of 20 sputum specimen of pulmonary tuberculosis, which were all positive detected by smear and culture, were positive. There were 15 specimen positive in 21 sputum with negative tested by smear and positive by culture. Besides, 5 of 19 sputum specimen with negative by smear and culture were positive detected by this method. CONCLUSION: The phage splitting assay can be used for rapid identification of Mycobacterium tuberculosis, which possesses high specificity and sensitivity for detection of Mycobacterium tuberculosis in sputum specimen. PMID- 11770424 TI - [Clinical research of pasinizid on retreated sputum positive pulmonary tuberculosis in senilities]. AB - OBJECTIVE: To observe and evaluate the effect and safety of pasinizid on treatment of the senile pulmonary tuberculosis with bacteriological positive. METHODS: 115 cases of the senile pulmonary tuberculosis with bacteriological positive were divided into therapy group(group A) and control group(group B1 and B2) randomly. Chemotherapy regimen: group A were treated by 3DZL2E/5DL2E mainly composed of pasinizid; group B1 were treated by 3HPZL2/5HL2E(abbreviated HP regimen); group B2 were treated by 3DZL2E/5DL2E(abbreviated SH regimen). RESULTS: When the chemotherapy was over, the sputum negative conversion rates were 92%, 72%, 71% in group A, group B1 and group B2 respectively. The conversion rate in group A was significantly higher than that in group B1 and group B2 (P < 0.05); focal absorption rates were 75%, 50%, 50% respectively, while the vanishing rates of cavity were 85%, 46%, 50% respectively. The rate in group A was significantly higher than that in group B1 and B2(P < 0.05); Rates of side effects were 17%, 58%, 18% respectively. The rates in group A and group B2 were apparently lower than that in group B1(P < 0.01). Bacteriological relapse rate of 2 years were 5%, 19%, 18%, respectively. The rate in group A was lower than that in group B1 and B2 (P < 0.01). CONCLUSIONS: The effect of pasinizid on senile retreated sputum positive pulmonary tuberculosis was better than HP and SH regimen. Due to its lower rates of side effects, it is recommended for clinical usage. PMID- 11770426 TI - [Interleukin-12 and the treatment of asthma]. PMID- 11770427 TI - [Recent research on mycobacteremia]. PMID- 11770428 TI - Heavy metal localisation in mycorrhizas of Epipactis atrorubens (Hoffm.) Besser (Orchidaceae) from zinc mine tailings. AB - The metal distribution within mycorrhizal and nonmycorrhizal roots of Epipactis atrorubens collected from zinc mine tailings and an area rich in heavy metal ores (both located in southern Poland) was investigated. The tailings, consisting of post-flotation material, were characterised by high levels of toxic elements such as Zn, Pb, and Cd, while soil outside the tailings was also strongly enriched in heavy metals. Atomic absorption spectrometry and proton-induced X-ray emission analysis revealed that heavy metals were mostly accumulated within orchid roots. Elemental maps from proton-induced X-ray emission showed that plant root epidermis and fungal coils which had developed within cortical cells of roots collected from the zinc mine tailings were the main places of Zn and Pb accumulation, associated with increased concentrations of Fe, Cd, Ti, Mn, Si, Ca, and S. The mean content of Pb and Zn in the coils was 4 to 5 times higher than in the root epidermis. In mycorrhizal roots from the tailings a statistically significant decrease in Pb and Zn content towards the inside of the root was observed. The mean content of Pb in coils from roots of plants growing outside the tailings was about 1% of the concentration in root coils from the tailings. Coils selected from orchid roots originating from a site outside the tailings contained comparatively high concentrations of Zn, Cd, and Cu, which was probably due to the high content of these elements in the soil. The results presented suggest a biofiltering effect against heavy metals by orchid mycorrhizal fungi. PMID- 11770429 TI - Nonsymbiotic hemoglobins in rice are synthesized during germination and in differentiating cell types. AB - Nonsymbiotic hemoglobins (ns-Hbs) previously have been found in monocots and dicots; however, very little is known about the tissue and cell type localization as well as the physiological function(s) of these oxygen-binding proteins. We report the immunodetection and immunolocalization of ns-Hbs in rice (Oryza sativa L.) by Western blotting and in situ confocal laser scanning techniques. Ns-Hbs were detected in soluble extracts of different tissues from the developing rice seedling by immunoblotting. Levels of ns-Hbs increased in the germinating seed for the first six days following imbibition and remained relatively constant thereafter. In contrast, ns-Hb levels decreased during leaf maturation. Roots and mesocotyls contained detectable, but low levels of ns-Hbs. Split-seed experiments revealed that ns-Hbs are synthesized de novo during seed germination and are expressed in the absence of any signal originating from the embryo. Immunolocalization of ns-Hbs by confocal microscopy indicated the presence of ns Hbs primarily in differentiated and differentiating cell types of the developing seedling, such as the aleurone, scutellum, root cap cells, sclerenchyma, and tracheary elements. To our knowledge, this is the first report of the specific cellular localization of these proteins during seedling development. PMID- 11770430 TI - In vivo 19F NMR chemical-shift imaging of Ancistrocladus species. AB - 19F nuclear magnetic resonance (NMR) imaging and 19F NMR chemical-shift imaging (19F CSI) have been used to localize fluorinated compounds administered to stems of Ancistrocladus heyneanus and A. abbreviatus for the elucidation of biosynthetic pathways in living plants. This first application of 19F CSI on plants proved CSI to be a valuable technique for mapping fluorinated molecules in plants. Exemplarily using trifluoroacetate as a model compound allowed to select appropriate feeding methods and to optimize both concentration and duration of the application to the plant. The time course of the uptake and distribution of trifluoroacetate was monitored by both 19F imaging and 19F CSI. Fluorinated metabolites formed by uptake of 3-fluoro-3-deoxy-D-glucose were detected with 19F CSI. PMID- 11770431 TI - Degradation of ribulose-bisphosphate carboxylase by vacuolar enzymes of senescing French bean leaves: immunocytochemical and ultrastructural observations. AB - The possible involvement of vacuolar cysteine proteinases in degradation of ribulose-bisphosphate carboxylase (Rubisco) in senescing French bean leaves was studied by ultrastructural and immunocytochemical analyses with antibodies raised against the large subunit (LSU) of Rubisco and SH-EP, a cysteine proteinase from Vigna mungo that is immunologically identical to one of the major proteinases of French bean plants. Primary leaves of 10-day-old plants were detached and placed at 25 degrees C in darkness for 0, 4, and 8 days to allow their senescence to proceed. The leaves at each senescence stage were subjected to the conventional electron microscopic and immunocytochemical studies. The results indicated that the chloroplasts of senescing French bean leaves were separated from the cytoplasm of the cell periphery and taken into the central vacuole and that the Rubisco LSU in the chloroplasts was degraded by vacuolar enzymes such as an SH-EP related cysteine proteinase that developed in senescing leaves. The present results together with the results of previous biochemical studies using vacuolar lysates support the view that Rubisco is degraded through the association of chloroplasts with the central vacuole during the senescence of leaves that were detached and placed in darkness. PMID- 11770432 TI - Freeze-substitution of dehydrated plant tissues: artefacts of aqueous fixation revisited. AB - This investigation assessed the extent of rehydration of dehydrated plant tissues during aqueous fixation in comparison with the fine structure revealed by freeze substitution. Radicles from desiccation-tolerant pea (Pisum sativum L.), desiccation-sensitive jackfruit seeds (Artocarpus heterophyllus Lamk.), and leaves of the resurrection plant Eragrostis nindensis Ficalho & Hiern. were selected for their developmentally diverse characteristics. Following freeze substitution, electron microscopy of dehydrated cells revealed variable wall infolding. Plasmalemmas had a trilaminar appearance and were continuous and closely appressed to cell walls, while the cytoplasm was compacted but ordered. Following aqueous fixation, separation of the plasmalemma and the cell wall, membrane vesiculation and distortion of cellular substructure were evident in all material studied. The sectional area enclosed by the cell wall in cortical cells of dehydrated pea and jackfruit radicles and mesophyll of E. nindensis increased after aqueous fixation by 55, 20, and 30%, respectively. Separation of the plasmalemma and the cell wall was attributed to the characteristics of aqueous fixatives, which limited the expansion of the plasmalemma and cellular contents but not that of the cell wall. It is proposed that severed plasmodesmatal connections, plasmalemma discontinuities, and membrane vesiculation that frequently accompany separation of walls and protoplasm are artefacts of aqueous fixation and should not be interpreted as evidence of desiccation damage or membrane recycling. Evidence suggests that, unlike aqueous fixation, freeze substitution facilitates reliable preservation of tissues in the dehydrated state and is therefore essential for ultrastructural studies of desiccation. PMID- 11770433 TI - Floral genes expressed in tomato hypocotyl explants in liquid culture. AB - This paper confirms, at molecular level, previous data showing that small explants of many plants do form a floral meristem and express specific floral genes after only few days in culture. After 15-20 days of culture, small tomato hypocotyl explants develop differentiated structures often resembling primitive ancestral reproductive organs. Other specific reproductive functions such as chromosomal segregation (somatic meiosis) were also present and demonstrated by means of a cytological and histological analysis. By reverse transcriptase-PCR and in situ hybridization it was found that these structures are indeed able to express flower-specific genes. The TM8 gene, a tomato gene that is expressed very early during floral development, is detectable on the proliferating hypocotyl explants during the first week of culture. The MON9612 gene, which in vivo is expressed only by tomato pistils and ovules, is detectable on the ovulelike structures developed after 20 days of culture. The construction of transgenic tomato plants expressing the GUS gene under the control of the MON9612 promoter allowed us to follow the induction and the expression of this gene during explant proliferation and development of the flowerlike structures. These data confirm the hypothesis that a floral reprogramming can be induced in plant explants as a consequence of wounding and growth factors action. It appears to be an effort to survive stress by means of an unscheduled reproductive program. PMID- 11770434 TI - Large amounts of apicoplast nucleoid DNA and its segregation in Toxoplasma gondii. AB - Apicoplasts (apicomplexan plastids) are nonphotosynthetic, secondary endosymbiotic plastids that are found in most apicomplexans. Although these organelles are essential for parasite survival, their functions, activities, and structures are not well understood. We examined the apicoplast nucleoid of Toxoplasma gondii from a morphological aspect by high-resolution epifluorescence microscopy and electron microscopy. We found unexpectedly large amounts of DNA in the nucleoid and the presence of several division-related structures. Initially, we identified the organellar nucleoids by staining with the DNA-specific dye 4',6 diamidino-2-phenylindole. A single nucleoid was observed per apicoplast, and the fluorescent spot representing the nucleoid was bright and spherical in contrast to the weak and filamentous spot representing the mitochondrial nucleoid. We also measured the DNA content of each apicoplast nucleoid by a video-intensified microscope photon-counting system and determined that the genomic copy number was at least 25, a figure over four times greater than that reported previously. Moreover, several groups of apicoplasts had significantly higher genomic copy numbers. The DNA molecules were accurately divided into two daughter apicoplasts just before nuclear division. In addition, we examined nucleoid segregation and the division apparatus using electron microscopy. However, we failed to observe nucleoid structures, suggesting that the apicoplasts are predominantly composed of nucleoid material. In addition, we observed "cap" structures at the termini of dividing apicoplasts, a possible plastid-dividing ring, and a microbody-like granule around the constriction. These structures may be involved in apicoplast division. PMID- 11770435 TI - Synchronous nuclear-envelope breakdown and anaphase onset in plant multinucleate cells. AB - Multinucleate plant cells with genetically balanced nuclei can be generated by inhibiting cytokinesis in sequential telophases. These cells can be used to relate the effect of changes in the distribution of nuclei in the cytoplasm to the control of the timing of cell cycle transitions. Which mitotic cell cycle events are sensitive to differences in the amount of cytoplasm surrounding each chromosomal complement has not been determined. To address this, we maximized the cell size by transiently inhibiting replication, while cell growth was not affected. The nuclei of 93% of the elongated cells reached prophase asynchronously compared to 46% of normal-sized multinucleate cells. The asynchronous prophases of normal-sized cells became synchronous at the time of nuclear-envelope breakdown, and the ensuing metaphase plate formation and anaphase onset and progression occurred synchronously. The elongated multinucleate cells were also very efficient in synchronizing the prophases at nuclear-envelope breakdown, in the prophase-to-prometaphase transition. However, 2.4% of these cells broke down the nuclear envelope asynchronously, though they became synchronous at the metaphase-to-anaphase transition. The kinetochore microtubular cycle, responsible for coordinating the metaphase-to-anaphase transition and for the rate of sister segregation to opposite spindle poles during anaphase, remained strictly controlled and synchronous in the different mitoses of a single cell, independently of differences in the amount of cytoplasm surrounding each mitosis or its ploidy. Moreover, the degree of chromosome condensation varied considerably within the different mitotic spindles, being higher in the mitoses with the largest surrounding cytoplasm. PMID- 11770436 TI - Cell division patterns of the protoderm and root cap in the "closed" root apical meristem of Arabidopsis thaliana. AB - The peripheral root cap and protoderm in Arabidopsis thaliana are organized into modular packets of cells derived from formative T-divisions of the root cap/protoderm (RCP) initials and subsequent proliferative divisions of their daughter cells. Each module consists of protoderm and peripheral root cap packets derived from the same periclinal T-division event of an RCP initial. Anatomical analyses are used to interpret the history of extensively coordinated cell divisions producing this modular construction. Within a given layer of root cap, the columella and RCP initials divided in a centrifugal sequence from the innermost columella initials toward the RCP initials. All RCP initials in the lineages around the circumference of the root divided nearly simultaneously in "waves" to form one module prior to the next wave of initial divisions forming a younger module. The peripheral root cap and protoderm packets within each module completed four rounds of proliferative divisions in the axial plane to produce, on average, 16 cells per packet in the basalmost modules in axial view. Peripheral root cap and protoderm cells predominantly in the T-type (trichoblast) lineages also underwent radial divisions as they were displaced basipetally. The regularity in the cellular pattern within the modules suggests a timing mechanism controlling highly coordinated cell division in the initials and their daughter cells. PMID- 11770437 TI - Modular construction of the protoderm and peripheral root cap in the "open" root apical meristem of Trifolium repens cv. Ladino. AB - Roots with open apical organization are defined by not having specific tiers of initial cells in the root apical meristem; those with closed apical organization have specific initial tiers to which all cell files can be traced. An example of the clear organization of closed roots is the development protocol of the root cap and protoderm. The key event in differentiating these tissues is the T division, a periclinal division of the root cap/protoderm (RCP) initial that establishes a module. Each module comprises two packets, the protoderm and peripheral root cap. Consecutive T-divisions of the same RCP initial produce up to five modules on average in a lineage of cells in white clover (Trifolium repens cv. Ladino), with all lineages around the circumference of the root dividing in "waves" to form one module prior to the next. On average, clover has approximately 32 axial protoderm and peripheral root cap cells in each module, and 32 RCP lineages. The occurrence of RCP T-divisions in white clover, a root with open apical organization, and the subsequent modular construction of the root cap and protoderm, provides a link between open and closed roots and suggests a common developmental feature that most roots of seed plants may share independent of their root meristem organization type. The open apical organization of the white clover root varies from roots with closed apical organization in that the RCP initials occur in staggered positions instead of connected to discrete tiers, and the peripheral root cap and columella daughter cells form additional layers of cells. White clover also forms root hairs on all protoderm cells irrespective of their position relative to the underlying cortical cells. PMID- 11770438 TI - In situ fixation of grape berries. AB - Usual immersion protocols in aldehyde solutions fail to fully preserve the fine structure of both exocarp and mesocarp cells of grape berries, especially for the veraison (onset of ripening) and post-veraison stages. In exocarp cells, fixative diffusion is hampered by the thick polysaccharide cell walls. In mesocarp cells, plasma membrane and tonoplast are disrupted before aldehyde cross-linking occurs, owing to the high osmotic pressure and cell wall texture. The fixative was therefore injected under pressure as small droplets in the outer and inner parts of the fruit, with limited changes in the steady-state organization of fruit tissues. Compared to a selective range of immersion protocols, a striking improvement in cell preservation was observed for all berry tissues, allowing new information on various compartments of grape berry cells. The preservation of organ integrity and local concentration of aldehyde molecules are the most critical parameters of improved fixation. This technique may be applicable to a large array of fleshy fruits containing mainly cells comprising a high volumetric proportion of vacuoles accumulating large amounts of organic acids and sugars and bounded by thick-walled exocarp cells. PMID- 11770439 TI - [Pulmonary thromboembolism -- current concepts]. AB - Pulmonary embolism is a common disorder and an important cause of morbidity and mortality. Since genetic predisposition appears to explain only about one fifth of cases, identification of other risk factors is critical. Pulmonary embolism ranges from incidental, clinically unimportant thromboembolism to massive embolism with sudden death. The initial diagnostic approach in patients with suspected pulmonary embolism commonly involves transesophageal echocardiography and ventilation-perfusion scanning. In patients with indeterminate findings on these exams, thoracic spiral computed tomography, magnetic resonance imaging and magnetic resonance angiography are promising. Pulmonary angiography is becoming less used because it is invasive and expensive. Unfractionated heparin is considered the treatment of choice for most patients with pulmonary embolism, except those with hemodynamic instability, who may need thrombolytic therapy. There is limited information on the efficacy and safety of low-molecular-weight heparin for the initial treatment of symptomatic pulmonary embolism. An up to date review of the international literature focused on epidemiology, pathophysiology, diagnosis, potential treatment and prognosis is presented. PMID- 11770440 TI - [Cardiac effects of acute poisoning with tricyclic antidepressants: systematic review of the literature -- Part IV]. AB - Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present this paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this fourth article (the last in a series), we present the prevention and management of tricyclic antidepressant overdose (in the three previous articles--published in previous issues of the Revista--we discussed the epidemiological aspects as well as the clinical presentation and the diagnosis, and the prognosis). Note: this is the fourth and last article on the cardiac toxicity of tricyclic antidepressant overdose. PMID- 11770441 TI - [National registry of non-invasive electrocardiology in 1999]. AB - The Portuguese Association of Arrhythmology. Pacing and Electrophysiology undertook a national registry on resources available in noninvasive laboratories in 1999. Forty-eight hospital centres answered the inquiry. Holter monitoring is an established technique, owned by all cardiology departments in the main hospitals and in 86% of district hospitals. The 40 centres with the technique have a total of 50 analysers and 166 recorders. The number of examinations performed was 14,046 in 1998 and 14,516 in 1999, which shows a remarkable stability. Ninety-three percent of equipments allow ST segment, 38% QT interval and 33% heart rate variability analysis. It is worth nothing the high activity of cardiopneumology technicians in the reading of the exams (94%). Late potential study is less spread. It is only possible in 38% of centers and between 1998 and 1999 the number of exams declined from 592 to 357. Only 12 centers have event recorders, nevertheless the number performed increased from 251 in 1998 to 283 in 1999. Finally, eight centres have tilt test facilities, but we do not have numbers of the examinations that were performed. PMID- 11770442 TI - Acute pulmonary embolism. PMID- 11770443 TI - [Guidelines for the diagnosis and treatment of chronic heart failure]. PMID- 11770444 TI - Outcome of cardiac arrests in a Portuguese hospital--evaluation of a hospital cardiopulmonar resuscitation program at one year. AB - OBJECTIVE: Evaluation of a hospital-wide resuscitation program at one year. METHODS: All records of cardiac arrest calls were collected, logged in a database by the same operator, and analyzed. The cardiac arrest teams consist of a physician and a nurse with ALS (Advanced Life Support) training. Each team has a radio that is activated by a single emergency number. Only cardiac arrest calls were analyzed. RESULTS: Between March 1999 and March 2000 there were 173 emergency team calls. Of these, 120 were cardiac arrest calls (90 in-hospital and 30 from the emergency room--out-of-hospital cardiac arrests). Of the 90 in hospital cardiac arrests, 61% were male, and median age was 73 years. In 90% of the calls, basic life support (BLS) was started before the arrival of the cardiac arrest team. The immediate cause was cardiac in 39% of the patients. Initial rhythm was ventricular fibrillation in 8%, asystole in 60% and other rhythms in 24% of the patients. Thirty percent presented return of spontaneous circulation (ROSC). There were no differences between those in whom BLS was started before the arrival of the cardiac arrest team and those in whom BLS had not been started. Ten patients (11%) were discharged from hospital. Of the 30 out-of hospital cardiac arrests, 70% were male, and median age was 69 years. In 97% BLS was started before the arrival of the cardiac arrest team. The immediate cause was cardiac in 30% of patients. Initial rhythm was ventricular fibrillation in 10%, asystole in 73% and other rhythms in 17% of the patients. ROSC was achieved in 27% of the patients. Three patients (10%) were discharged from hospital. There were no differences either in ROSC or in survival to hospital discharge between in-hospital and out-of-hospital cardiac arrests. The state of health previous to cardiac arrest was significantly different between in- and out-of-hospital cardiac arrests: 3% versus 32% healthy, with no functional limitation. The authors conclude that: first, the current records do not enable all the desired goals of the "Utstein style" to be achieved and need to be reviewed; second, 90 to 97% of BLS previous to the arrival of the cardiac arrest team is a good indication of the efficiency of the hospital-wide program, which included training in BLS for all the hospital staff; third, the survival rate, although in accordance with much of the literature, could be improved. PMID- 11770445 TI - Cardiopulmonary resuscitation and the Portuguese Society of Cardiology. PMID- 11770446 TI - Mortality and morbidity trends in ischemic heart disease in the autonomous region of Madeira in the ten-year period 1987-1996. AB - The increase in absolute number of deaths from ischemic heart disease (IHD) in the population aged > or = 65 years, in both sexes, in Madeira, when comparing the years 1987 and 1996, led to significant increases in the corresponding standardized death rates that go against the stabilization seen at national level. Significant increases in these rates for the same years were also seen in the district of Beja and in the Azores. The aim of this study was to ascertain the trends for the incidence, morbidity and mortality from acute myocardial infarction (AMI) in patients admitted in Madeira and its contribution to the increase in these rates, particularly in the population aged < 65 years of both sexes, which the number of deaths from ischemic heart disease did not increase. We studied 119 pts with AMI admitted in 1987 (year A), of whom 53 were aged < 65 years, and 186 pts with AMI admitted in 1996 (year B), of whom 72 were aged < 65 years, whose data were included in the Madeira Ischemic Heart Disease Register (RECIMA), an IHD hospital register that covers 1792 patients admitted with AMI in the Coronary Intensive Care Unit of the Department of Medical and Surgical Cardiology of Funchal Hospital over a period of 15 years (1984-1998). Mortality by the 28th day (fatal AMI admissions) in all ages fell slightly in both sexes in the two years studied (A = 19.3%; B = 16.1%). The number of fatal AMI admissions rose among females in the two age groups considered A = 11; B = 20; delta% = +45) and fell among males (A = 12; B = 10; delta% = -20). In males aged > or = 65 years, this number remained the same (A = 7; B = 7) and fell in males aged > or = 65 years (A = 5; B = 3; delta% = -40). The number of pts who survived to the 28th day (non-fatal AMI admissions) rose in all age groups for both sexes (A = 96; B = 156; delta% = +38.46), as did the ratios with deaths from IHD. These increases were roughly double in the group of patients aged 65 years compared to patients aged < 65 years. We found highly significant positive correlations in the population aged < 65 years between the number of non-fatal AMI admissions (morbidity data) and the number of deaths from IHD (mortality data) recorded in every year of the 10-year period 1987-96, these values being highly significant in both sexes (r = 0.89; p < 0.0001), in males (r = 0.87; p < 0.0001) and in females (r = 0.77; p < 0.0001). Since our study was carried out on an island on which all AMI cases are admitted to a single treatment center, we can conclude that these positive correlations represent a trend towards worsening of morbidity and mortality from IHD in Madeira in the population aged < 65 years, even though the number of deaths from IHD did not rise. The establishment of IHD registers similar to RECIMA in other regions of the country would help to identify trends in morbidity, mortality, and morbidity plus mortality in this population that would be useful in improving the orientation of resources allocated to the prevention and treatment of cardiovascular diseases. PMID- 11770447 TI - Pulmonary transvalvular and venous flows in the estimation of left ventricular diastolic pressures. A comparative Doppler-catheterization study. AB - OBJECTIVES: To evaluate the association between patterns of pulmonary transvalvular and venous flows in patients with ischemic heart disease, assessed by Doppler echocardiography, and invasive measurements of left ventricular (LV) diastolic pressures. POPULATION: Thirty-seven patients with clinical diagnosis or suspicion of coronary heart disease and referred for coronary angiography; all were in sinus rhythm, and had no known valvular heart or chronic pulmonary disease. METHODS: The following were recorded during transthoracic Doppler echocardiography: acceleration time (AT) and total ejection time (ET) of right ventricular outflow; duration of the flow at atrial contraction (a duration) and duration of the "A" wave of mitral inflow (A duration). These data were correlated with the values of LV filling pressures previously obtained by cardiac catheterization. RESULTS: We found a significant correlation of LV end-diastolic pressures with the difference a-A duration (r = 0.75; p < 0.001) and also with the ratio AT/ET (r = -0.73;. PMID- 11770448 TI - [Introduction to oto-mandibular dysplasias or "20 years after"]. PMID- 11770449 TI - [Hemifacial microsomia. Embryological and clinical approach]. AB - Hemifacial microsomia is an otomandibular dysplasia which includes congenital malformations affecting the jaw and ear apparatus. The knowledge of normal embryonic development is a prerequisite for optimal clinical management of those malformations. The development of craniofacial structures is a multi-step process, which involves many developmental events ranging from the migration of neural crest cells from the neural folds of the young neurula embryo to molecular signaling interactions that coordinate outgrowth and patterning of the facial primordia. Our current knowledge of craniofacial development is limited, but the use of animal developmental models will contribute significantly to our understanding of human otomandibular dysplasias. In this review we discuss both the classical and current aspects of otomandibular development. A clinical approach to hemifacial microsomia is proposed. Current pathogenetic hypotheses of hemifacial microsomia and also mandibulofacial dysostosis are reviewed. PMID- 11770450 TI - [Oto-mandibular dysplasias: genetics and nomenclature of syndromes]. AB - Otomandibular dysplasia are characterised by a combination of anomalies of the ear and the mandible. From the surgical point of vue, facial dysostosis is prominent and focus the attention. For the geneticist it is a group of different entities, familial or sporadic. Familial history, detailed clinical examination looking for extra-facial associated malformations, characteristics of the facial dysostosis, unilaterality or bilaterality and biological or radiological findings allow sometimes to identify a known syndrome. A bilateral and symetric dysostosis with predominant zygomatic and malar hypoplasia suggest the diagnosis of Treacher Collins or Franceschetti syndrome or mandibulofacial dysostosis, particularly in the presence of positive familial history. Acral anomalies associated with facial dysostosis allow the distinction between Treacher-Collins syndrome and acrofacial dysostosis (Nager and Miller syndromes). Unilateral and bilateral asymmetrical anomalies, namely facioauriculovertebral syndrome, hemifacial microsomia, otomandibular dysostosis, no. 7 cleft, first branchial arch syndrome, Goldenhar syndrome were lumping together by Gorlin in 1990, who proposed to use the term "oculoauriculovertebral spectrum". This classification is the first step before genetic studies, who need homogeneous group of patients. Lastly recurrence risk can be evaluated and genetic counselling can be done only if a precise genetic diagnosis is known. PMID- 11770451 TI - [Diagnosis of facial and craniofacial asymmetry]. AB - Craniofacial asymmetry is caused by various aetiologies but clinical examination remains the most important criteria since minor asymmetry is always present. The diagnosis can be confirmed by anthropometric measurements and radiological examinations but only severe asymmetries or asymmetries with an associated functional impairment should be treated. The treatment depends on the cause, and on the time of appearance. Congenital asymmetries might be treated early, during the first year of life if a craniosynostosis is present. Hemifacial microsomia are treated later if there is no breathing impairment. Since the pediatricians have recommended the dorsal position for infant sleeping, an increasing number of posterior flattening of the skull has been appearing, and could be prevented by adequate nursing. Other causes of craniofacial asymmetries are rare and should be adapted to the cause (tumors, atrophies, neurological paralysis, hypertrophies) by a specialized multidisciplinar team. PMID- 11770452 TI - [Imaging of oto-mandibular dysplasias]. AB - The modern imaging opened a possibility of precise exploration of otomandibular dysplasias. The techniques of browsing by IRM and CT Scan and the software of image processing which is associated with these techniques (three-dimensional, superposition and removing of the anatomical structures) allow to carry out a true anatomical dissection of the whole of these malformative syndromes. The study of the skeletal anomalies gains by specifying the disorders of development of the various mandibular segments: temporomandibular joint, ramus and horizontal branch and also, all cranio-maxillar structures: orbital rim, cranial basis. Study of masticatory muscles shows an important damage correlated with skeletal troubles and performs a grading of morphological and functional gravity. This analytical study emphasizes some malformative axis: malar axis in cases of mandibulofacial dystosis, temporomandibular axis in hemifacial microsomia. Modern imaging can appreciate, by development of three-dimensional cephalometry, growth anomalies and quantification of post therapeutical results. At last usefulness of imaging appears in therapeutic modelisation and in the field of Computer-Aided Planning of surgical techniques of osteotomies and overall maxillaries distractions. PMID- 11770453 TI - [Auricular reconstruction in cases of microtia. Principles, methods and classification]. AB - In the correction of microtia, whether it be isolated or associated to other facial anomalies, the same principles are followed: sculpture of a framework from autologous rib cartilage to reproduce the contours of an ear and coverage of the framework with the cutaneous remnants. The sculpting of the cartilaginous framework requires sufficient training which through experience becomes the most routine surgical step of the reconstruction. Regarding the cutaneous step, it is different, because the microtia may appear in multiple forms. Numerous clinical classifications have already been published. The new classification which has been proposed, enables a better understanding of the cutaneous step of microtia correction. It is a surgical classification. Three different types of skin plasties (type 1, 2 and 3) allow for the treatment of all microtia. Thus, a surgical proposal can be advocated as early as the clinical examination regarding the appropriate utilization of the cutaneous remnants. PMID- 11770454 TI - [Microtia in cases of oto-mandibular dysplasia]. AB - The technique of reconstruction of a microtia, observed in cases of otomandibular dysplasia, does not differ in its principle from that of an isolated microtia. The technical approach depends primarily on the aspect of the auricular remnants whose forms are multiple and are in no way etiologically specific. However, when associated with other malformations of otomandibular dysplasia, the microtia presents some particularities and its correction must be integrated in the global treatment of hemifacial anomalies. PMID- 11770455 TI - [Mandibular growth, its environmental interactions]. AB - A thorough knowledge of mandibular growth is necessary for proper comprehension of growth disorders and malformations affecting the lateral cranio-facial region. The growth mechanisms are complex and multifactorial, the mandible itself is subdivided into two heterogeneous and interdependent segments, as far as growth is concerned. These are the ramus and the corpus. The ramus is interacting with the middle cranial base through the TMJ and the temporo-pterygoid muscle belt. The mandibular body is interacting with the maxilla and the anterior cranial base. Its occlusal role is a function of the adaptive capacity of the alveolodental region. PMID- 11770456 TI - [Morphological alterations of oto-mandibular syndromes]. AB - Otomandibular dysplasia is a congenital malformation defined by a certain degree of temporomandibular or pterygomandibular hypoplasia. The syndrome is characterised by the variability of clinical findings, but the three major features are auricular, mandibular and maxillary hypoplasia. All the laterofacial structures may be affected. The deformity is usually unilateral but bilateral cases exist; a lot of associated malformations have been described. Multiple classification systems have been published. Some of them are very complex, but it is possible to define a simple diagnostic diagram based on ethiopathogenic data. Bilateral involvement affects predominantly the zygoma, and concerns hereditary syndromes. When the mandibular hypoplasia is evident Franceschetti or Goldenhar syndrome is suspected; otherwise Treacher-Collins syndrome is probable. Unilateral cases are not, in general, hereditary and the hypoplasia predominates on the mandible. The difference between hemifacial microsomia or mandibular dysplasia is made by the presence of associated laterofacial deformities. PMID- 11770457 TI - [Mandibular elongation and remodeling by gradual distraction. An experience of 277 cases]. AB - Distraction osteogenesis at the craniofacial skeleton offers superior results than using standard osteotomies and other surgical techniques when treating mandibular hypoplasia. After ten years, we have performed 221 patients with hemifacial microsomia and 56 patients with micrognathia using external mandibular distraction. For every single patient the distraction vector is different according to the degree of bone hypoplasia. The bone elongation ranged from 12 to 49 mm, and the results were excellent: facial symmetry was reestablished, the menton became horizontal and the long term result controls shows stability clinically and occlusally. PMID- 11770458 TI - [Hemifacial microsomia treated with mandibular lengthening using intraoral distractors. On precise indications]. AB - Mandibular hypoplasia in the hemifacial microsomia have largely benefited from distraction techniques especially intraoral. In fact, these techniques are possible in the child, replacing him in a better morphological, psychological and functional configuration. They can redynamise growth and, in any case, diminish secondary distant effects. The authors, from precise criteria, propose a surgical classification to facilitate the therapeutic decision. Intraoral and sometimes bidirectional distraction, whose results are equivalent to external distraction, present numerous advantages that, in the majority of cases, make it preferred now to external distraction. Its three-dimensional (3D) effect on bone and soft tissues and the long term follow-up must be evaluated more objectively, as pre and post-distraction stereolithographic or 3D photogrammetric may get. It must be considered in the child as the first step of skeletic surgery preparing to a facilitated second step orthopedic, orthodontic or orthognathic after puberty. In the young adult, it is in competition with conventional surgery but the slow progressive process, kind with the temporo-mandibular joints, allows in mandibular asymmetries an adaptation having avoided the need for controlateral osteotomy or a bone graft. PMID- 11770459 TI - [Oto-mandibular dysplasias: indications for conventional osteotomies and costochondral graft]. AB - Conventional osteotomies and bone grafts are still indicated in the treatment of otomandibular dysplasia. Results are achieved rapidly with a minimum of discomfort for the patient. In the mild cases, a complete correction can be obtained in a single operation. PMID- 11770460 TI - [Vascularized bone grafts in the treatment of hemifacial microsomia]. AB - A systematic and theoretic review is performed on the vascularised bone donor sites that may be useful in the case of hemifacial microsomia. A review of the literature reveals that the iliac crest and the scapula are the most commonly used vascularised bone grafts. A case study is included in the paper, showing an hemifacial microsomia reconstruction using a composite fibular vascularised bone graft. They highlight the criterias they think fundamental for choosing the vascularised bone graft donor site regarding the aims of the reconstruction of a Pruzansky grade II or III. PMID- 11770461 TI - [Reconstructive surgery of the soft tissue in hemifacial microsomia]. AB - Hypoplasia of soft tissues constitutes one of the major elements of hemifacial microsomia. Despite the fact that it occurs in 95% of cases of microsomia, hypoplasia is one aspect of the syndrome that is often neglected. The authors, by a general review of the relevant literature, describe the quantitative and qualitative importance of hypoplasia, as well as its statistical rapport with other elements of the syndrome. In studying the different treatments available for hypoplasia of soft tissues, several factors stand out. New techniques of bone distraction have transformed surgical indications by allowing an extension of soft tissues, particularly of skin. The treatment of hypoplasia follows two major axes; firstly, the use of grafts by injection of adiposal tissue for cases in which the deficit is only moderate, and secondly, microsurgical flaps, mainly of the fasciocutaneous type, for the relatively small portion of cases (9%) in which the deficit is more severe. By first analysing any constraints due to the treatment of bone and ear malformations, the schedule of the different stages of necessary surgery can be effectively planned. PMID- 11770462 TI - [Facial paralysis in oto-mandibular dysplasia. Clinical study and therapeutic implications]. AB - The percentage of facial palsy in the otomandibular dysostosis is great. It varies from 12 to 50% in the literature. The OMENS classification embodies the muscular and facial nerve defects, and appears to represent the most inclusive classification. Few literature reviews have proposed a treatment of the facial palsy in the otomandibularis dysostosis. The authors proposed a treatment protocol depending on the patient's age. The patients before one year of age are treated with the Inigo's technique, which provide reinnervation to the affected muscles through a crossed facial nerve graft. After one-year old, the surgical approach is realised at five to seven years old to permit a physical therapy. The upper lip is reanimated by the lengthening temporalis myoplasty or by free muscle transplantation with nerve graft. The orbital area treatment of the paralyzed side can included a lengthening of the upper eyelid levator muscle, an asymmetric lateral tarsorraphy and a chondromucous graft. PMID- 11770463 TI - [Auditory aspects of congenital malformations of the external and middle ears]. AB - Auricular malformations are frequently associated to malformations of the external, the middle, and the inner ear in variable degrees. Asystematic audiometry must be performed in case of unilateral facial microsomia. This test which can be performed in very young patients can detect bilateral ear malformations necessitating auditory rehabilitation by surgery or external hearing aids. In major ear aplasia, air conduction hearing aids can rarely be proposed. In this case, bone conduction hearing aids using a mastoid transducer of through a bone anchored device yield the best auditory results with an excellent local tolerance. PMID- 11770464 TI - [Summary of the report. Planning of treatment of oto-mandibular dysostoses]. PMID- 11770465 TI - Introduction to the special section on families and religion: a call for a recommitment by researchers, practitioners, and policymakers. AB - Although religion is an important aspect of human experience, the topic is rarely evident in psychology journals. To correct this omission was the goal of this special section on families and religion. In the introduction to the section several reasons for the neglect of this topic are noted as well as the relevance of religion for family research and practice. The contributions of the articles in this section are highlighted. Finally, recommendations for a future research agenda are offered and the clinical implications of this topic are examined. PMID- 11770466 TI - Religion in the home in the 1980s and 1990s: a meta-analytic review and conceptual analysis of links between religion, marriage, and parenting. AB - The authors reviewed 94 studies published in journals since 1980 on religion and marital or parental functioning. Meta-analytic techniques were used to quantify religion-family associations examined in at least 3 studies. Greater religiousness appeared to decrease the risk of divorce and facilitate marital functioning, but the effects were small. Greater Christian conservatism was modestly associated with greater endorsement and use of corporal punishment with preadolescents. Isolated findings suggested that greater parental religiousness relates to more positive parenting and better child adjustment. The scope, meaningfulness, and potential strength of findings were restricted because of reliance on global or single-item measures of religious and family domains. To facilitate more conceptually and methodologically sophisticated research, the authors delineated mechanisms by which the substantive and psychosocial elements of religion could benefit or harm family adjustment. PMID- 11770467 TI - Finding meaning in religious practices: the relation between religious holiday rituals and marital satisfaction. AB - This study examined the relation between marital satisfaction and religious holiday ritual practices. One hundred twenty couples, married 9 years on average, completed measures of religious holiday practices (current family and family-of origin) and marital satisfaction. Couples were interviewed about how important religion was to their family life. Marital satisfaction was related to religious holiday rituals beyond a global indication of religiousness. A different pattern was found for husbands and wives, with husbands' satisfaction more closely linked to ritual meaning and wives' satisfaction associated with routine practices. Family-of-origin rituals were connected across generations. Wives' marital satisfaction was related to husbands' report of religious holiday rituals but not the converse. Results are discussed in terms of how rituals affirm relationships, connect values and beliefs, and may have differential meaning for men and women. PMID- 11770468 TI - Understanding the relationship between religiosity and marriage: an investigation of the immediate and longitudinal effects of religiosity on newlywed couples. AB - The association between religiosity and marital outcome has been repeatedly demonstrated, but a complete understanding of this relationship is hindered by limitations of theory and method. The purpose of the current study was to test 3 explanatory models by assessing 2 samples of newlywed couples. Findings indicated that religiosity was associated with attitudes toward divorce, commitment, and help seeking cross-sectionally. Longitudinal effects, however, were most consistent with a moderating model, wherein religiosity had a positive impact on husbands' and wives' marital satisfaction for couples with less neurotic husbands and a negative impact for couples with more neurotic husbands. Overall, the impact of religiosity was weak over the first 4 years of marriage. Theoretical propositions are offered to guide future research in delineating the types of marriages that may be most affected by religiosity. PMID- 11770469 TI - Transmission and transaction: predicting adolescents' internalization of parental religious values. AB - Data in this study supported a model of internalization that included both transmission and transactional variables. Two sets of hierarchical linear regression models were conducted on data collected from the fathers, mothers, and adolescents (10 to 12 years old) in 171 intact Caucasian families. One set predicted adolescent religious behavior; the other predicted the importance of religion to child. Transmission variables (parental religious behavior and parental desire for child to be religious) predicted the most variance in all models. Dyadic discussions of faith (transactional) predicted significant variance in all models. Child gender had a direct effect only on adolescent religious behavior. A significant 3-way interaction occurred between child gender, parental desire for child to be religious, and dyadic discussions when predicting importance of religion to child, with child and parent gender dyads interacting in a complex manner. PMID- 11770471 TI - Religion and the science of relationships: is a happy marriage possible? AB - The current article is a commentary on the 4 articles included in this issue regarding religion and the family. Recommendations are made regarding the methodological strategies that might be followed in enhancing the science of religion and family. The 4 articles in this issue are used as examples of how the field can fruitfully proceed in the future. Foremost among the recommendations is that specific hypotheses be developed to explore explicit ways in which certain aspects of religious life might relate to specific aspects of family/marriage functioning. PMID- 11770470 TI - Varieties of religion-family linkages. AB - The 4 articles in this special issue make important contributions to both family and religious studies as well as to their interface. This commentary begins by considering 4 unifying themes present across all of the articles, including meaningful religion-family linkages, the importance of gender differences in the faith-family interface, the significance of intergenerational relationships, and the need for better theory. The authors then discuss the unique major strength and secondary limitations of each study. Finally, the commentary focuses on two challenges inhibiting the contemporary study of religion and the family--a relative lack of racial and religious diversity in samples and the lack of a unifying theory of religion-family linkages--and suggests how to adjust the trajectory of future theory and research to address these issues. PMID- 11770472 TI - Psychology, religion, and the family: it's time for a revival. AB - Despite some occasional efforts to link psychology, religion, and the family, psychological research has largely ignored the topic. Three fundamental psychological questions about the role of religion in the family are raised. The publication of the 4 studies in this issue represents a watershed in this area, and these articles provide a model for future research. However, several pitfalls in this area of research are identified. These pitfalls are primarily due to the complexity of religion and heterogeneity associated with it. Four research directions are then recommended. It is concluded that this area is ripe for a research revival. PMID- 11770473 TI - Parenting beliefs and behaviors in northern and southern groups of Italian mothers of young infants. AB - Similarities and differences in northern and southern Italian mothers' social and didactic parenting beliefs and behaviors, and relations between their beliefs and behaviors, are reported. Both groups of mothers reported that they engaged more in social than didactic interactions with their infants, whereas in actuality both groups engaged in didactic behaviors with their infants for longer periods of time than they engaged in social behaviors. In addition, northern mothers engaged in more social interactions with their infants than did southern mothers. No correlations between beliefs and behaviors emerged in either group. These data speak to issues of intracultural variation and cross-cultural similarities in family psychology and parenting, belief-behavior relations in parenting, and the importance of methodology (parental report or observation) in the study of parenting and family functioning. PMID- 11770474 TI - Mothers' and fathers' interactions with preschoolers in the home in northern Thailand: relationships to teachers' assessments of children's social skills. AB - Using ecocultural theory as a guide, the authors observed some everyday activities of mothers and fathers with children for 2 hr in the home in 53 families residing in Chaing Mai Province in northern Thailand. Teachers provided assessments of children's general social skills in preschool using the Preschool Kindergarten Behavior Scale (K. W. Merrell, 1994). Mothers were significantly more likely to engage in basic care, general conversations, and educational activities; to praise; and to use commands and reasoning as forms of discipline with children than fathers. Mothers and fathers did not significantly differ in the display of affection, teasing or joking, and modes of play interactions with children. Parents generally treated boys and girls similarly. Few associations between parent-child involvement and children's social skills in preschool were significant. Data are discussed with respect to changes in culturally driven parent-child practices. PMID- 11770475 TI - Effects of interpersonal control, perspective taking, and attributions on older mothers' and adult daughters' satisfaction with their helping relationships. AB - Older mother-adult daughter dyads (N = 44) were interviewed separately about 3 variables hypothesized to affect satisfaction with the help provided to mothers by their daughters: feelings of interpersonal control, perspective-taking abilities, and attributions made about the self and other dyad member during positive and negative helping interactions. The most important predictors of partner satisfaction were mothers' and daughters' ability to accurately perceive the partner's feelings about the helping relationship and their feelings of interpersonal control. The most salient predictors of mothers' and daughters' own satisfaction were the attributions they made about the partner during a negative helping situation and their feelings of interpersonal control. These findings underscore the importance of considering interpersonal psychological variables in research concerned with helping relationships in later life. PMID- 11770476 TI - Fathers' participation in family research: is there a self-selection bias? AB - The representativeness of fathers who participate in family research was examined among 661 families. Approximately two thirds of eligible fathers participated. Mothers' and observers' reports on families of participating and non participating fathers were compared. Participating fathers underrepresented fathers with less education, later-born children, more ambivalent marriages, partners with more traditional child-rearing beliefs, families with less optimal parenting environments, and infants who were unplanned, had more difficult temperaments, and were less healthy. Also underrepresented were ethnic minority families and working-class fathers. However, no differences were found in regard to child gender, family income, mothers' psychosocial functioning, either parent's employment experiences, or child-care arrangements. Implications for the generalizability of findings and the recruitment of fathers are discussed. PMID- 11770477 TI - Attributions in marriage: examining the entailment model in dyadic context. AB - The entailment model of attributions is examined for the first time using a dyadic approach and longitudinal data. In a sample of 229 married partners with children, causal attributions were distinguished empirically from responsibility attributions and, consistent with the entailment model, the effect of causal attributions on conflict was mediated through attributions of responsibility. Only 1 path was influenced by spouse gender. Examination of cross-spouse effects revealed significant effects and provided a better fit than a model with no cross spouse effects. The importance of including cross-spouse effects in attributional models is discussed. PMID- 11770478 TI - Understanding infidelity: correlates in a national random sample. AB - Infidelity is a common phenomenon in marriages but is poorly understood. The current study examined variables related to extramarital sex using data from the 1991-1996 General Social Surveys. Predictor variables were entered into a logistic regression with presence of extramarital sex as the dependent variable. Results demonstrated that divorce, education, age when first married, and 2 "opportunity" variables--respondent's income and work status--significantly affected the likelihood of having engaged in infidelity. Also, there were 3 significant interactions related to infidelity: (a) between age and gender, (b) between marital satisfaction and religious behavior, and (c) between past divorce and educational level. Implications of these findings and directions for future research are discussed. PMID- 11770479 TI - Can skills training prevent relationship problems in at-risk couples? Four-year effects of a behavioral relationship education program. AB - Eighty-three couples were stratified into groups at high and low risk for relationship distress and randomized to either the Self-Regulatory Prevention and Relationship Enhancement Program (Self-PREP) or a control condition. As predicted, there were differential effects of Self-PREP on high-risk and low-risk couples. Because of low statistical power, results must be interpreted cautiously, but at 1-year follow-up high-risk couples in Self-PREP showed trends toward better communication than control couples. However, there was no difference in the communication of Self-PREP and control low-risk couples. High risk couples receiving Self-PREP exhibited higher relationship satisfaction at 4 years than control couples, but in low-risk couples relationship satisfaction was higher in the control condition. High-risk couples seemed to benefit from skills based relationship education, but low-risk couples did not. PMID- 11770481 TI - Late returns from an early start. PMID- 11770480 TI - Omega-3 fatty acids in the treatment of depression. PMID- 11770483 TI - Suggestions to a potential seller. PMID- 11770482 TI - Sedation in the 21st century. Dental Sedation Teachers Group Symposium, Cardiff 2001. PMID- 11770484 TI - The Rorschach Inblot Test: a debate. The value of Rorschach assessment. PMID- 11770486 TI - Unexpected electrolyte changes in a vomiting man. AB - A 27 year old man presented with 24 hours of unexplained vomiting. His past health was unremarkable except for a deep vein thrombosis one year earlier. At that time his serum electrolytes were normal. The results of repeat electrolyte measurement are shown in Table 1. PMID- 11770487 TI - HRT and breast changes. AB - S K is a sensible, fit 53 year old with irritating menopausal symptoms who wants to discuss hormone replacement therapy (HRT). She has had a previous mammogram which described moderately dense breasts with only fair visibility for discrete lesions. More recently she had a screening mammogram at BreastScreen, and received a routine 'all clear' letter. You believe that HRT can relieve her symptoms. PMID- 11770485 TI - Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. AB - Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism. PMID- 11770488 TI - Return to work: conducting a worksite assessment. AB - George is a 46 year old who, at work, develops back pain with right sided sciatica. Initial findings include an absent right ankle jerk with sensory loss in the distribution of the right S1 nerve root. MRI scan confirms the diagnosis of an L5-S1 disc herniation with pressure on the right S1 nerve root. Following referral to a neurosurgeon he undergoes microdiscectomy. He is now six weeks postoperative. The scar healed well. His sciatica and ankle jerk have improved. He is now considering returning to work. PMID- 11770489 TI - Visual vignette. Cushing's syndrome due to ectopic production of ACTH by a bronchial carcinoid. PMID- 11770490 TI - Community participation in determining the needs of users and carers of rural community care services. Highland Community Care Forum. AB - In this paper we present the methods and key outcomes of a community led needs assessment exercise. The needs assessment sought to enhance the development of rural community care services by ensuring the views of users and carers were secured and considered in joint planning processes. The research was developed by members of the North and West Sutherland Community Care Forum. A community profiling template was developed and employed in five parish areas of Sutherland. This was drawn from 45 interviews with key informants and 2 community workshops, In addition 54 users and carers were interviewed. The outcomes of the needs assessment exercise identified geographical and cultural factors which present difficulties in developing services as well as posing barriers to user involvement. PMID- 11770491 TI - [Pharmacies in Rzeszow (17th-19th centuries)]. AB - This dissertation is available thanks to many years investigation into the development of education and the history of the church in Galicia and the surrounding region. On the basis of gathered record materials and works concerning medical care, the author presents a history of drug stores in Rzezow in 17th-19th centuries. First, he deals with a pharmacy run by the Pijar monks in the years 1670-1697. There is a unique polychromy in it showing the different way of treating sick patients in the years 1695-1697. Next, he depicts the development of pharmacies according to Austrian law, when southern Poland came under the rule of the Habsburg family between 1772-1918. The lot of all pharmacies, the role of their owners, illustrious pharmacists, Polish - Austrian marriages among pharmacists, their connections with doctors and their position in society during this period are also described. PMID- 11770492 TI - [Raspail's camphor chest]. AB - In the 19th century many medical textbooks were published in Poland. These presented the principles of medical knowledge, including information about illnesses and medicines. Most of them were written by physicians or pharmacists but some of them were written by charlatans. Books describing "miracle cures" were specially popular and often had many editions. The book Domowy lekarz i domowa apteka written by F. V. Raspail and published in Warsaw in 1864 is a good example of bad medical advice. The main medicine recommended by Raspail was camphor. PMID- 11770493 TI - [The history of correction of refractive errors: spectacles]. AB - An historical analysis of discoveries related to the treatment of defects of vision is described. Opinions on visual processes, optics and methods of treating myopia, hypermetropia and astigmatism from ancient times through the Middle Ages, the renaissance and the following centuries are presented in particular. The beginning of the usage of glasses is discussed. Examples of the techniques which have been used to improve the subjective and objective methods of measuring refractive errors are also presented. PMID- 11770494 TI - [The history of correction of refractive errors: refractive surgery]. AB - The evolution of particular methods of refractive surgery is presented including the origins of radial keratotomy, relaxing incisions, keartophakia, epiferatophakia and keratomileusis as well as recent adaptation of lasers for the surgical treatment of refractive error. Such famous persons as Barraquer, Sato, and Fidorov are discussed in particular. The history not only of great achievements but also of some of the false ideas which accompanied efforts to obtain the emmetropia is presented. PMID- 11770495 TI - [Changing views in the 20-th century regarding acute appendicitis]. AB - In 1886 Reginald H. Fitz described the pathology of acute appendicitis suggested surgical treatment. 10 years later, during VII-th the Congress of Polish Surgeons in Cracow, Maksymilian Rutkowski was the first in Poland to present the results of that kind of treatment. Operations performed for that frequently, not seldom fatal disease-were not accepted from the beginning through the world. In Poland as well at the beginning of the 20-th century, indications for appendectomy were discussed. In 1920 previous views regarding the necessity for surgical treatment in acute and chronic cases changed. These changes were supported by the observation that in some cases involving pain in the right, pain remains even after appendectomy were the vermiform appendix was found to be unaffected and it was also found that adhesion of ileus can be a dangerous late complications. It might appear that today's knowledge relating to this disease is fully established. Close observation found successful results as shown by in decreasing mortality. Within 100 years in the Massachusetts General Hospital mortality feel from 40% to 0.8% to Fitzs between patients who had undergone appendectomy accompany high percentage failed preoperative diagnosis. Today at the beginning of the 21-st century with the availability of MRI, CT, videosurgery and organs transplant it is difficult to imagine that the cause of such a common disease is still unknown and that in almost 1/4 of the operations performed on patients do not confirm the preoperative diagnosis. PMID- 11770496 TI - Diagnostic dilemma. PMID- 11770497 TI - Blood flow changes to the femoral head after acetabular fracture or dislocation in the acute injury and perioperative periods. PMID- 11770498 TI - Factors predictive of immobilization complications in pediatric polytrauma. PMID- 11770499 TI - Lag screw only fixation of the lateral malleolus. PMID- 11770500 TI - Total SF-36 scores as [a] functional outcome measure. PMID- 11770501 TI - Update: Investigation of bioterrorism-related anthrax--Connecticut, 2001. AB - CDC and state and local health departments continue investigating cases of bioterrorism-related anthrax. This report revises the number of suspected cases and updates the investigation of a 94-year-old Connecticut (CT) resident who died from inhalational anthrax. PMID- 11770502 TI - Update: Unexplained deaths following knee surgery--Minnesota, 2001. AB - Since November 13, 2001, the Minnesota Department of Health (MDH), in collaboration with CDC, has been conducting an investigation of three patients who died unexpectedly within 1 week following knee surgery. Patient 1 had received a knee osteochondral allograft, and patients 2 and 3 had undergone total knee replacement surgery. Epidemiologic and microbiologic investigations have not linked the deaths of the three patients. PMID- 11770503 TI - Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts--Florida and Louisiana, 2000. AB - In the United States, approximately 50,000 knee surgeries are performed each year for repairing anterior cruciate ligament (ACL) injuries. Tissue allografts frequently are used for ACL reconstruction, and septic arthritis is a rare complication of such procedures. This report describes four patients who acquired postsurgical septic arthritis probably associated with contaminated bone-tendon bone allografts used for ACL reconstruction. Effective sterilization methods that do not functionally alter musculoskeletal tissue are needed to prevent allograft related infections. PMID- 11770504 TI - Influenza activity--United States, 2001-02 season. AB - In collaboration with the World Health Organization (WHO) and its collaborating laboratories, National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories, state and local health departments, and a network of sentinel physicians, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in circulating strains of influenza viruses. This report summarizes influenza activity in the United States during September 30 November 24, 2001, when the viruses isolated most frequently were influenza A (H3N2). These viruses were well matched antigenically by the 2001-02 influenza A (H3N2) vaccine. Vaccine supplies are plentiful and influenza vaccine should continue to be offered during December and later. PMID- 11770505 TI - Use of onsite technologies for rapidly assessing environmental Bacillus anthracis contamination on surfaces in buildings. AB - Environmental sampling to ascertain the presence of Bacillus anthracis spores in buildings is an important tool for assessing risk for exposure. Similar to diagnostic testing, culture with positive identification of B. anthracis (CDC culture method) is the confirmatory test. Laboratory-based polymerase chain reaction (PCR) methods for detecting genetic material of B. anthracis can be used in preliminary assessments and as adjuncts to microbiologic methods. Although these tests are consistent with culture results, PCR methods are not approved by the Food and Drug Administration, and results should not be the basis for clinical decisions. PMID- 11770506 TI - Colorectal cancer awareness month brings about new guidelines for screening, prevention. PMID- 11770507 TI - New method of colorectal cancer diagnosis and surgery may improve quality of life. PMID- 11770508 TI - Clot-buster proves safe, effective when given during first three hours after a stroke. PMID- 11770509 TI - Atlanta HMOs overcome competitive fires to form common guidelines. PMID- 11770510 TI - Helping patients evaluate quality of alternative medicine. PMID- 11770511 TI - Compliance with asthma management guidelines is low. PMID- 11770512 TI - Study establishes best practice for the prevention of urinary tract infections. PMID- 11770513 TI - AHRQ releases 20 tips to help prevent medical errors. PMID- 11770514 TI - Revised treatment and testing guidelines for latent tuberculosis infection. PMID- 11770515 TI - Exception to eukaryotic rules. PMID- 11770516 TI - Etymology of epigenetics. PMID- 11770517 TI - Speciation and centromere evolution. PMID- 11770518 TI - Tapping science's women for the podium. PMID- 11770519 TI - Proceedings of the 1st International Workshop on Space Radiation Research and 11th Annual NASA Space Radiation Health Investigators' Workshop, Arona (Italy), May 27-31, 2000. PMID- 11770520 TI - Space radiation research in the new millenium--from where we come and where we go. AB - Space radiation research had a significant impact in the past. The physical interaction of heavy charged particles with living matter and the development of models, including microdosimetry, were stimulated by problems encountered in space. New phenomena were discovered. Advanced dosimetric techniques had to be developed and computational methods to describe the radiation field in space. The understanding of the radiobiology of heavy ions, necessary for a well-founded risk assessment and prompted by space radiation research, constitutes also the basis for heavy ion radiotherapy. So far unknown areas like the interaction of microgravity and radiation were opened. The space station will give even more opportunities. For the first time it will be possible to investigate animals for a longer time under the influence of both microgravity and radiation. Living systems can be exposed under well defined conditions with parallel physical measurements. Solar particle events are still an unsolved problem. Significant improvement in their predictability and quantitative description can be expected. All this will not only give exciting opportunities for research but will also translate into immediate benefit for human beings. This paper will attempt to give an overview of the past achievements and glance into the future. PMID- 11770521 TI - New techniques in hadrontherapy: intensity modulated proton beams. AB - Inverse planning and intensity modulated (IM) X-ray beam treatment techniques can achieve significant improvements in dose distributions comparable to those obtained with forward planned proton beams. However, intensity modulation can also be applied to proton beams and further optimization in dose distribution can reasonably be expected. A comparative planning exercise between IM X-rays and IM proton beams was carried out on two different tumor cases: a pediatric rhabdomyosarcoma and a prostate cancer. Both IM X-rays and IM protons achieved equally homogenous coverage of the target volume in the two tumor sites. Predicted NTCPs were equally low for both treatment techniques. Nevertheless, a reduced low-to-medium dose to the organs at risk and a lesser integral non-target mean dose for IM protons in the two cases favored the use of IM proton beams. PMID- 11770522 TI - A Monte Carlo code for a direct estimation of radiation risk. AB - An example of pragmatic approach for predicting mixed field effects is presented. The method was initially applied adopting the following, commonly used, assumptions: a) radiation risk (typically cancer) is correlated with chromosome aberration induction; b) radiation-induced chromosome-exchange yield can be well described by a linear-quadratic dependence on particle fluences (mostly linear with high-LET radiation), with parameters depending on particle types and energies. Information on monochromatic field radiobiological effects was integrated in a condensed-history Monte Carlo transport code (FLUKA), able to simulate nuclear interactions. The integrated code provides the chromosome aberration yield (and thus an estimation of radiation risk) in each voxel of any irradiated volume, given any external mixed-field irradiation; in the present work, the method was tested for neutron irradiation of a water phantom. FLUKA was then coupled with a geometrical human phantom provided with different radiation shielding, in order to apply this approach to estimate radiation risk in manned space missions. PMID- 11770523 TI - Visual assessment of the radiation distribution in the ISS Lab module: visualization in the human body. AB - The US Lab module of the International Space Station (ISS) is a primary working area where the crewmembers are expected to spend majority of their time. Because of the directionality of radiation fields caused by the Earth shadow, trapped radiation pitch angle distribution, and inherent variations in the ISS shielding, a model is needed to account for these local variations in the radiation distribution. We present the calculated radiation dose (rem/yr) values for over 3,000 different points in the working area of the Lab module and estimated radiation dose values for over 25,000 different points in the human body for a given ambient radiation environment. These estimated radiation dose values are presented in a three dimensional animated interactive visualization format. Such interactive animated visualization of the radiation distribution can be generated in near real-time to track changes in the radiation environment during the orbit precession of the ISS. PMID- 11770524 TI - Monte Carlo simulation of charged particle transport in biomatter. AB - Knowledge of the microscopic distribution of interactions in irradiated matter is of fundamental importance for a mechanistic understanding of subsequent effects. This may be obtained by Monte Carlo codes which simulate event-by-event the transport of charged particles in matter. The development of such codes necessitates accurate interaction cross-sections for all the important collision processes. A semi-theoretical formalism has been developed and implemented in a Monte Carlo code which fairly accurately predicts energy-loss spectra for charged particle impact on water molecules. The extension of the formalism for establishing the necessary cross-sections for liquid/solid water (i.e. more realistic biomatter) is discussed and preliminary results are presented. PMID- 11770525 TI - A reference radiation facility for dosimetry at flight altitude and in space. AB - A reference facility for the intercomparison of active and passive detectors in high-energy neutron fields is available at CERN since 1993. A positive charged hadron beam (a mixture of protons and pions) with momentum of 120 GeV/c hits a copper target, 50 cm thick and 7 cm in diameter. The secondary particles produced in the interaction are filtered by a shielding of either 80 cm of concrete or 40 cm of iron. Behind the iron shielding, the resulting neutron spectrum has a maximum at about 1 MeV, with an additional high-energy component. Behind the concrete shielding, the neutron spectrum has a pronounced maximum at about 70 MeV and resembles the high-energy component of the radiation field created by cosmic rays at commercial flight altitudes. The facility is used for a variety of investigations with active and passive neutron dosimeters. Its use for measurements related to the space programme is discussed. PMID- 11770526 TI - Proton Irradiation Facility and space radiation monitoring at the Paul Scherrer Institute. AB - The Proton Irradiation Facility (PIF) has been designed and constructed, in cooperation between Paul Scherrer Institute (PSI) and European Space Agency (ESA), for terrestrial proton testing of components and materials for spacecraft. Emphasis has been given to generating realistic proton spectra encountered by space-flights at any potential orbit. The facility, designed in a user-friendly manner, can be readily adapted to the individual requirements of experimenters. It is available for general use serving also in testing of radiation monitors and for proton experiments in different scientific disciplines. The Radiation Environment Monitor REM has been developed for measurements of the spacecraft radiation conditions. Two instruments were launched into space, one into a Geo stationary Transfer Orbit on board of the STRV-1b satellite and one into a Low Earth Orbit on the Russian MIR station. The next generation of monitors (SREMs- Standard REMs) is currently under development in partnership of ESA, PSI and Contraves-Space. They will operate both as minimum intrusive monitors, which provide radiation housekeeping data and alert the spacecraft when the radiation level crosses allowed limits and as small scientific devices measuring particle spectra and fluxes. Future missions as e.g. INTEGRAL, STRV-1c and PROBA will be equipped with new SREMs. PMID- 11770528 TI - Measurement of the depth distribution of average LET and absorbed dose inside a water-filled phantom on board space station MIR. AB - The Atominstitute of the Austrian Universities developed the HTR-method for determination of absorbed dose and "averaged" linear energy transfer (LET) in mixed radiation fields. The method was applied with great success during several space missions (e.g. STS-60, STS-63, BION-10 and BION-11) and on space station MIR in the past 10 years. It utilises the changes of peak height ratios in LiF thermoluminescent glowcurves in dependence on the LET. Due to the small size of these dosemeters the HTR-method can be used also for measurements inside tissue equivalent phantoms. A water filled phantom with a diameter of 35 cm containing four channels where dosemeters can be exposed in different depths was developed by the Institute for Biomedical Problems. This opens the possibility to measure the depth distribution of the average LET and the dose equivalent simultaneously. During phase 1 dosemeters were exposed for 271 days (05.1997-02.1998) in 6 different depths inside the phantom, which was positioned in the commander cabin. In phase 2 dosemeters were exposed in 2 channels in 6 different depths for 102 days (05.1998-08.1998) in the board engineer cabin, following an exposure in different channels in 3 different depths for 199 days (08.1998- 02.1999) in the Modul KWANT 2. PMID- 11770527 TI - Nuclear detecting systems at LNL and LNS: foreseen experiments to provide basic data for heavy-ion risk assessment. AB - The use of existing detecting systems developed for nuclear physics studies allows collecting data on particle and ion production cross-sections in reactions induced by Oxygen and Carbon beams, of interest for hadrontherapy and heavy-ion risk assessment. The MULTICS and GARFIELD apparatus, together with the foreseen experiments, are reviewed. PMID- 11770529 TI - What we can learn from heavy ion therapy for radioprotection in space. AB - A major problem in manned space flight is the impact of cosmic radiation, especially that of heavy charged particles since they have an elevated biological efficiency (RBE). The RBE estimation determines the potential exposure for man. It is one of the limiting factors for space flight and should be known very precisely. The same is true for heavy-ion tumor therapy where beams of carbon ions are used to treat deep-seated tumors. There, RBE values determine the dose distribution and are estimated using the Local Effect Model (LEM). The clinical results confirm the correctness of LEM and suggest to use the same theoretical approach to assess the impact of cosmic rays. PMID- 11770530 TI - Shielded Heavy-Ion Environment Linear Detector (SHIELD): an experiment for the Radiation and Technology Demonstration (RTD) Mission. AB - Radiological assessment of the many cosmic ion species of widely distributed energies requires the use of theoretical transport models to accurately describe diverse physical processes related to nuclear reactions in spacecraft structures, planetary atmospheres and surfaces, and tissues. Heavy-ion transport models that were designed to characterize shielded radiation fields have been validated through comparison with data from thick-target irradiation experiments at particle accelerators. With the RTD Mission comes a unique opportunity to validate existing radiation transport models and guide the development of tools for shield design. For the first time, transport properties will be measured in free-space to characterize the shielding effectiveness of materials that are likely to be aboard interplanetary space missions. Target materials composed of aluminum, advanced composite spacecraft structure and other shielding materials, helium (a propellant) and tissue equivalent matrices will be evaluated. Large solid state detectors will provide kinetic energy and charge identification for incident heavy-ions and for secondary ions created in the target material. Transport calculations using the HZETRN model suggest that 8 g cm -2 thick targets would be adequate to evaluate the shielding effectiveness during solar minimum activity conditions for a period of 30 days or more. PMID- 11770531 TI - Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune. AB - The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses. PMID- 11770532 TI - BNL accelerator-based radiobiology facilities. AB - For the past several years, the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (USA) has provided ions of iron, silicon and gold, at energies from 600 MeV/nucleon to 10 GeV/nucleon, for the US National Aeronautics and Space Administration (NASA) radiobiology research program. NASA has recently funded the construction of a new dedicated ion facility, the Booster Applications Facility (BAF). The Booster synchrotron will supply ion beams ranging from protons to gold, in an energy range from 40-3000 MeV/nucleon with maximum beam intensities of 10(10) to 10(11) ions per pulse. The BAF Project will be described and the future AGS and BAF operation plans will be presented. PMID- 11770533 TI - Research activities at the Loma Linda University and Proton Treatment Facility- an overview. AB - The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation. PMID- 11770534 TI - The Italian hadrontherapy project CNAO. AB - In 1991 INFN was first involved in R&D work in the field of hadrontherapy. In 1992 the TERA Foundation was created with the purpose of forming and employing people fully devoted to the design, promotion and construction of hadrontherapy centres in Italy and in Europe. This contribution reviews the present status of therapy with ion beams and describes the main TERA project CNAO (Centro Nazionale di Adroterapia Oncologica) based on the optimised medical synchrotron designed in the framework of the "Proton Ion Medical Machine Study" (PIMMS) carried out at CERN from 1996 to 1999 with CERN, the Med-AUSTRO project, GSI, Oncology 2000 (Prague) and TERA as partners. PMID- 11770535 TI - Monte Carlo track structure for radiation biology and space applications. AB - Over the past two decades event by event Monte Carlo track structure codes have increasingly been used for biophysical modelling and radiotherapy. Advent of these codes has helped to shed light on many aspects of microdosimetry and mechanism of damage by ionising radiation in the cell. These codes have continuously been modified to include new improved cross sections and computational techniques. This paper provides a summary of input data for ionizations, excitations and elastic scattering cross sections for event by event Monte Carlo track structure simulations for electrons and ions in the form of parametric equations, which makes it easy to reproduce the data. Stopping power and radial distribution of dose are presented for ions and compared with experimental data. A model is described for simulation of full slowing down of proton tracks in water in the range 1 keV to 1 MeV. Modelling and calculations are presented for the response of a TEPC proportional counter irradiated with 5 MeV alpha-particles. Distributions are presented for the wall and wall-less counters. Data shows contribution of indirect effects to the lineal energy distribution for the wall counters responses even at such a low ion energy. PMID- 11770537 TI - Once we know all the radiobiology we need to know, how can we use it to predict space radiation risks and achieve fame and fortune? AB - It has been over 40 years since occupational radiation exposures to NASA's astronauts began and more than 300 individuals have been exposed to low and intermediate doses of trapped protons and galactic cosmic rays (GCR). The International Space Station (ISS) will add substantially to this number and significantly increase average lifetime doses. We review these exposures in this report. After many years of investigation, the method used to assess risk have not changed significantly. However, molecular biology and genetics have made enormous progress in establishing the mechanisms of cancer formation, damage to the central nervous system, and individual variation in sensitivity to radiation. We discuss critical questions and possible new approaches to the prediction of risk from space radiation exposures. Experimental models can lead to testable theories that along with extensive biophysical and informatics approaches, will lead to fame and fortune by allowing for accurate projections of astronaut risks and for the development of biological countermeasures. PMID- 11770536 TI - Recent measurements for hadrontherapy and space radiation: nuclear physics. AB - The particles and energies commonly used for hadron therapy overlap the low end of the charge and energy range of greatest interest for space radiation applications, Z=1-26 and approximately 100-1000 MeV/nucleon. It has been known for some time that the nuclear interactions of the incident ions must be taken into account both in treatment planning and in understanding and addressing the effects of galactic cosmic ray ions on humans in space. Until relatively recently, most of the studies of nuclear fragmentation and transport in matter were driven by the interests of the nuclear physics and later, the hadron therapy communities. However, the experimental and theoretical methods and the accelerator facilities developed for use in heavy ion nuclear physics are directly applicable to radiotherapy and space radiation studies. I will briefly review relevant data taken recently at various accelerators, and discuss the implications of the measurements for radiotherapy, radiobiology and space radiation research. PMID- 11770538 TI - New measurements for hadrontherapy and space radiation: biology. AB - The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made. PMID- 11770539 TI - Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health. AB - NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health. PMID- 11770540 TI - Optimized shielding for space radiation protection. AB - Future deep space mission and International Space Station exposures will be dominated by the high-charge and -energy (HZE) ions of the Galactic Cosmic Rays (GCR). A few mammalian systems have been extensively tested over a broad range of ion types and energies. For example, C3H10T1/2 cells, V79 cells, and Harderian gland tumors have been described by various track-structure dependent response models. The attenuation of GCR induced biological effects depends strongly on the biological endpoint, response model used, and material composition. Optimization of space shielding is then driven by the nature of the response model and the transmission characteristics of the given material. PMID- 11770541 TI - The FLUKA radiation transport code and its use for space problems. AB - FLUKA is a multiparticle transport code capable of handling hadronic and electromagnetic showers up to very high energies (100 TeV), widely used for radioprotection and detector simulation studies. The physical models embedded into FLUKA are briefly described and their capabilities demonstrated against available experimental data. The complete modelling of cosmic ray showers in the earth atmosphere with FLUKA is also described, and its relevance for benchmarking the code for space-like environments discussed. Finally, the ongoing developments of the physical models of the code are presented and discussed. PMID- 11770543 TI - Overview of active methods for shielding spacecraft from energetic space radiation. AB - During the 1960's and into the early 1970's, investigations were conducted related to the feasibility of using active radiation shielding methods, such as afforded by electromagnetic fields, as alternatives to passive, bulk material shielding to attenuate space radiations. These active concepts fall into four categories: (1) electrostatic fields; (2) plasma shields; (3) confined magnetic fields; and (4) unconfined magnetic fields. In nearly all of these investigations, consideration was given only to shielding against protons or electrons, or both. During the 1980's and 1990's there were additional studies related to proton shielding and some new studies regarding the efficacy of using active methods to shield from the high energy heavy ion (HZE particle) component of the galactic cosmic ray spectrum. In this overview, each concept category is reviewed and its applicability and limitations for the various types of space radiations are described. Recommendations for future research on this topic are made. PMID- 11770542 TI - Radiation protection using Martian surface materials in human exploration of Mars. AB - To develop materials for shielding astronauts from the hazards of GCR, natural Martian surface materials are considered for their potential as radiation shielding for manned Mars missions. The modified radiation fluences behind various kinds of Martian rocks and regolith are determined by solving the Boltzmann equation using NASA Langley's HZETRN code along with the 1977 Solar Minimum galactic cosmic ray environmental model. To develop structural shielding composite materials for Martian surface habitats, theoretical predictions of the shielding properties of Martian regolith/polyimide composites has been computed to assess their shielding effectiveness. Adding high-performance polymer binders to Martian regolith to enhance structural properties also enhances the shielding properties of these composites because of the added hydrogenous constituents. Heavy ion beam testing of regolith simulant/polyimide composites is planned to validate this prediction. Characterization and proton beam tests are performed to measure structural properties and to compare the shielding effects on microelectronic devices, respectively. PMID- 11770544 TI - Development of a space radiation Monte Carlo computer simulation based on the FLUKA and ROOT codes. AB - This NASA funded project is proceeding to develop a Monte Carlo-based computer simulation of the radiation environment in space. With actual funding only initially in place at the end of May 2000, the study is still in the early stage of development. The general tasks have been identified and personnel have been selected. The code to be assembled will be based upon two major existing software packages. The radiation transport simulation will be accomplished by updating the FLUKA Monte Carlo program, and the user interface will employ the ROOT software being developed at CERN. The end-product will be a Monte Carlo-based code which will complement the existing analytic codes such as BRYNTRN/HZETRN presently used by NASA to evaluate the effects of radiation shielding in space. The planned code will possess the ability to evaluate the radiation environment for spacecraft and habitats in Earth orbit, in interplanetary space, on the lunar surface, or on a planetary surface such as Mars. Furthermore, it will be useful in the design and analysis of experiments such as ACCESS (Advanced Cosmic-ray Composition Experiment for Space Station), which is an Office of Space Science payload currently under evaluation for deployment on the International Space Station (ISS). FLUKA will be significantly improved and tailored for use in simulating space radiation in four ways. First, the additional physics not presently within the code that is necessary to simulate the problems of interest, namely the heavy ion inelastic processes, will be incorporated. Second, the internal geometry package will be replaced with one that will substantially increase the calculation speed as well as simplify the data input task. Third, default incident flux packages that include all of the different space radiation sources of interest will be included. Finally, the user interface and internal data structure will be melded together with ROOT, the object-oriented data analysis infrastructure system. Beyond the benefits of 'objectivity', ROOT's incorporation will also provide a graphical user interface with powerful tools for input prior to the calculation, as well as for data analysis and visualization of the results. PMID- 11770545 TI - Creation and utilization of a World Wide Web based space radiation effects code: SIREST. AB - In order for humans and electronics to fully and safely operate in the space environment, codes like HZETRN (High Charge and Energy Transport) must be included in any designer's toolbox for design evaluation with respect to radiation damage. Currently, spacecraft designers do not have easy access to accurate radiation codes like HZETRN to evaluate their design for radiation effects on humans and electronics. Today, the World Wide Web is sophisticated enough to support the entire HZETRN code and all of the associated pre and post processing tools. This package is called SIREST (Space Ionizing Radiation Effects and Shielding Tools). There are many advantages to SIREST. The most important advantage is the instant update capability of the web. Another major advantage is the modularity that the web imposes on the code. Right now, the major disadvantage of SIREST will be its modularity inside the designer's system. This mostly comes from the fact that a consistent interface between the designer and the computer system to evaluate the design is incomplete. This, however, is to be solved in the Intelligent Synthesis Environment (ISE) program currently being funded by NASA. PMID- 11770546 TI - Neutron environments on the Martian surface. AB - Radiation is a primary concern in the planning of a manned mission to Mars. Recent studies using NASA Langley Research Center's HZETRN space radiation transport code show that the low energy neutron fluence on the Martian surface is larger than previously expected. The upper atmosphere of Mars is exposed to a background radiation field made up of a large number of protons during a solar particle event and mixture of light and heavy ions caused by galactic cosmic rays at other times. In either case, these charged ions interact with the carbon and oxygen atoms of the Martian atmosphere through ionization and nuclear collisions producing secondary ions and neutrons which then interact with the atmospheric atoms in a similar manner. In the past, only these downward moving particles have been counted in evaluating the neutron energy spectrum on the surface. Recent enhancements in the HZETRN code allow for the additional evaluation of those neutrons created within the Martian regolith through the same types of nuclear reactions, which rise to the surface. New calculations using this improved HZETRN code show that these upward moving neutrons contribute significantly to the overall neutron spectrum for energies less than 10 MeV. PMID- 11770548 TI - Consensus guidelines outline drug selection and sequencing options for bipolar disorder. PMID- 11770547 TI - Comparative treatment planning using secondary cancer mortality calculations. AB - Calculations of mortality due to secondary cancer have been investigated for its use in comparative treatment planning. A patient with Hodgkin's disease has been chosen as an example and has been planned with different radiation treatment modalities using photons and protons. The ICRP calculation scheme has been used to calculate mortality from dose distributions. To this purpose target volumes as well as critical structures have been outlined in the CT set of a patient with Hodgkin's disease. Dose distributions have been calculated using conventional as well as intensity modulated treatment techniques using photon and proton radiation. From the mean doses of each organ the mortality has been derived. Our work suggests that calculations of mortality can be useful in comparative treatment planning. Such mortality calculations can be helpful to find decisions between radiotherapy treatment techniques (intensity modulated or conventional treatment) or between different types of radiation (photons, electrons, protons, neutrons). PMID- 11770549 TI - Tennessee, Ohio health care organizations dramatically improve stroke diagnosis and treatment. PMID- 11770550 TI - Educate patients and staff with do-not-resuscitate Q&A list. PMID- 11770551 TI - New clinical advisory on systolic blood pressure issued. PMID- 11770552 TI - Hospital-school asthma prevention collaboration improves outcomes for both. PMID- 11770553 TI - Intensive care patients recover faster when allowed to waken. PMID- 11770554 TI - Countywide initiative lowers heart and cancer death rates. PMID- 11770556 TI - Joint Commission revises standards for behavioral health care. PMID- 11770555 TI - Treating blood clots at home made easier with new guidelines. PMID- 11770557 TI - End-of-life program increases hospice referrals and patient satisfaction. PMID- 11770558 TI - Wireless technology facilitates consistent cardiac monitoring. PMID- 11770560 TI - Space-age heart monitoring technology moves to inpatient and outpatient health care settings. PMID- 11770561 TI - Longer hospice length of stay tied to community outreach initiatives. PMID- 11770562 TI - Hospitals unite to improve breast cancer treatment. PMID- 11770563 TI - Early aspirin use lowers the risk of further stroke and death in acute ischemic stroke patients. PMID- 11770564 TI - Study shows children need less anesthesia under Bispectral Index (R) monitoring. PMID- 11770565 TI - Suicide prevention kit seeks to curb national epidemic of teen suicides. PMID- 11770566 TI - Catholic health care. PMID- 11770567 TI - Brain death and the philosophical significance of the process of development of, and cessation of, consciousness in arousal and awareness in the human person. PMID- 11770568 TI - Physicians ought not kill. PMID- 11770569 TI - Is the early embryo a person? PMID- 11770570 TI - The unity of the human person: a central concept in the interface between medicine and theology. PMID- 11770571 TI - The ethics of fetal tissue transplant research: a review. PMID- 11770572 TI - The sophistication of Ellis Island in prenatal diagnosis with subsequent "selective termination" of babies with disabilities. PMID- 11770573 TI - Moral and the medical considerations in the management of extrauterine pregnancy. PMID- 11770574 TI - Christ, physician and patient, the model for Christian healing. PMID- 11770575 TI - Human cloning and Donum Vitae. PMID- 11770576 TI - Promoting oral health: interventions for preventing dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries. A report on recommendations of the task force on community preventive services. AB - The Task Force on Community Preventive Services (the Task Force) has conducted systematic reviews of the evidence of effectiveness of selected population-based interventions to prevent and control dental caries (tooth decay), oral (mouth) and pharyngeal (throat) cancers, and sports-related craniofacial injuries. The Task Force strongly recommends community water fluoridation and school-based or school-linked pit and fissure sealant delivery programs for prevention and control of dental caries. Using the rules of evidence it has established, the Task Force found insufficient evidence of effectiveness or ineffectiveness of the remaining interventions reviewed. Therefore, the Task Force makes no recommendation for or against use of statewide or communitywide sealant promotion programs, population-based interventions for early detection of precancers and cancers, or population-based interventions to encourage use of helmets, facemasks, and mouthguards to reduce oral-facial trauma in contact sports. The Task Force's finding of insufficient evidence indicates the need for more research on intervention effectiveness. Until the results of such research become available, readers are encouraged to judge the usefulness of these interventions by other criteria. This report presents additional information regarding the recommendations, briefly describes how the reviews were conducted, and provides information designed to help apply the strongly recommended interventions locally. PMID- 11770577 TI - School health guidelines to prevent unintentional injuries and violence. AB - Approximately two thirds of all deaths among children and adolescents aged 5-19 years result from injury-related causes: motor-vehicle crashes, all other unintentional injuries, homicide, and suicide. Schools have a responsibility to prevent injuries from occurring on school property and at school-sponsored events. In addition, schools can teach students the skills needed to promote safety and prevent unintentional injuries, violence, and suicide while at home, at work, at play, in the community, and throughout their lives. This report summarizes school health recommendations for preventing unintentional injury, violence, and suicide among young persons. These guidelines were developed by CDC in collaboration with specialists from universities and from national, federal, state, local, and voluntary agencies and organizations. They are based on an in depth review of research, theory, and current practice in unintentional injury, violence, and suicide prevention; health education; and public health. Every recommendation is not appropriate or feasible for every school to implement. Schools should determine which recommendations have the highest priority based on the needs of the school and available resources. The guidelines include recommendations related to the following eight aspects of school health efforts to prevent unintentional injury, violence, and suicide: a social environment that promotes safety; a safe physical environment; health education curricula and instruction; safe physical education, sports, and recreational activities; health, counseling, psychological, and social services for students; appropriate crisis and emergency response; involvement of families and communities; and staff development to promote safety and prevent unintentional injuries, violence, and suicide. PMID- 11770578 TI - Hemorrhagic complication of anticoagulation during pregnancy in a woman with lupus anticoagulant. AB - BACKGROUND: Lupus anticoagulant is an acquired antiphospholipid antibody that can increase greatly the risk of thromboembolism during pregnancy. Because a baseline elevated activated partial thromboplastin time (PTT) is associated frequently with this antibody, monitoring anticoagulant effect with activated PTT can be unreliable. CASE: A pregnant woman with lupus anticoagulant being treated with adjusted dose heparin experienced concurrent severe thrombotic and hemorrhagic complications. CONCLUSION: This case illustrates the pitfall of activated PTT monitoring when administering anticoagulation therapy to a patient with a baseline elevated activated PTT. We propose that heparin levels be used to monitor anticoagulation in these patients. PMID- 11770579 TI - Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy. AB - BACKGROUND: The treatment of heparin-induced thrombocytopenia in pregnancy is uncertain. Warfarin is contraindicated and ancrod is of unknown safety. Low molecular-weight heparin should not be used because of cross-reactivity with unfractionated heparin. We report a case of heparin-induced thrombocytopenia during pregnancy treated successfully with danaparoid. CASE: A 25-year-old woman pregnant with twins developed heparin-induced thrombocytopenia after starting heparin therapy for a deep vein thrombosis. Treatment was initiated with danaparoid by subcutaneous injection and was continued until the time of delivery. Treatment was completed with 6 weeks of warfarin therapy postpartum. No fetal or maternal ill effects were observed. CONCLUSION: Danaparoid, which has low cross-reactivity for heparin-dependent antibodies and no known fetopathic effects, was used successfully to treat our patient, who developed heparin induced thrombocytopenia during pregnancy. Danaparoid may be the treatment of choice for this difficult clinical situation in which there are limited therapeutic options. PMID- 11770580 TI - Intravenous iron therapy for severe pregnancy anemia with high erythropoietin levels. AB - BACKGROUND: To demonstrate that intravenous (IV) iron therapy rapidly can secure the physiologic correction of severe nonhemorrhagic anemia more safely than blood component therapy and recombinant erythropoietin treatment. CASE: An 18-year-old woman with beta-thalassemia in her 33rd week of gestation had a hemoglobin level of 4.8 g/dL and an erythropoietin value of 191 mU/mL. After IV iron administration, erythropoietin rapidly decreased and hemoglobin increased to 8.1 g/dL in correlation with estriol elevation. A healthy infant with normal hemoglobin and ferritin levels was delivered at 42 weeks by cesarean. CONCLUSION: Intravenous iron administration rapidly corrected severe nonhemorrhagic anemia in a pregnant patient and may produce an improvement in fetal indices. High erythropoietin levels predict a good response to iron and may obviate the need for blood transfusions and recombinant erythropoietin administration, at least until this therapy is tried. PMID- 11770581 TI - Castleman disease in pregnancy. AB - BACKGROUND: Castleman disease, a rare disorder characterized by benign proliferation of lymphoid tissues, generally presents as a solitary mediastinal mass. We report the first case of this disease during pregnancy. CASE: A 32-year old woman presented with a large abdominal mass and vaginal bleeding during the second trimester of pregnancy. Abdominal ultrasound demonstrated a large, retroperitoneal solid mass of mixed echogenicity and increased vascularity. The patient underwent explorative laparotomy that revealed a mesenteric mass, histologically consistent with Castleman disease of the hyaline-vascular type. The mass was excised completely, and the immediate postoperative course was uneventful, although the patient went into spontaneous preterm labor during the 29th week of pregnancy. CONCLUSION: Castleman disease should be considered one of the benign etiologies for an abdominal or retroperitoneal mass during pregnancy. PMID- 11770582 TI - Severe folate deficiency masquerading as the syndrome of hemolysis, elevated liver enzymes, and low platelets. AB - BACKGROUND: Although folate deficiency is common in pregnancy, progression to megaloblastosis is not. Hemolytic anemia, thrombocytopenia, and coagulopathy due to folate deficiency may mimic the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). CASES: Two women presented in the second trimester with abdominal pain and severe thrombocytopenia. These symptoms were misinterpreted in the first woman as the HELLP syndrome, leading to an emergency cesarean delivery. Subsequent investigation revealed folate deficiency; treatment resulted in rapid normalization of all abnormalities. In the second woman, folate deficiency was diagnosed antenatally. Treatment allowed continuation of the pregnancy to term. CONCLUSION: The serious complications of folate deficiency make a strong case for supplementation in pregnancy. Careful scrutiny of clinical and laboratory findings may help discriminate the HELLP syndrome from its mimics, avoiding preterm delivery. PMID- 11770583 TI - Acute reactive hepatitis in pregnancy induced by alpha-methyldopa. AB - BACKGROUND: Alpha-methyldopa is an antihypertensive medication used commonly in pregnancy. Reactive hepatitis is a severe, uncommon reported side effect of this medication. To our knowledge, there has been only one other reported case of alpha-methyldopa-induced hepatitis associated with pregnancy in the United States. CASE: A patient at 17 weeks' estimated gestational age was evaluated for elevated maternal serum alpha-fetoprotein, which is used generally as a screening test for birth defects. A thorough history, physical examination, and laboratory evaluation were performed, and alpha-methyldopa-induced maternal hepatitis was diagnosed. CONCLUSION: The astute clinician should include maternal hepatic dysfunction in the differential diagnosis of an elevated maternal serum alpha fetoprotein and should consider obtaining aminotransferase levels after initiation of alpha-methyldopa therapy during pregnancy. PMID- 11770584 TI - Haloperidol overdose during pregnancy. AB - BACKGROUND: Suicide attempts during pregnancy are rare. Over-the-counter and psychotropic medications are most commonly used. Although intentional overdose of haloperidol has been reported in nonpregnant adults, it has not, to our knowledge, been reported previously during pregnancy. In this case of suicide attempt by haloperidol overdose, maternal and fetal responses were studied extensively. CASE: Intentional ingestion of 300 mg haloperidol by a pregnant woman at 34 weeks' gestation caused maternal unresponsiveness, an extrapyramidal reaction, temporary fetal akinesia, and a nonreactive nonstress test. The mother recovered in 48 hours. The fetus did not reach a biophysical profile score of ten until 5 days after presentation. CONCLUSION: Haloperidol overdose during pregnancy causes a maternal extrapyramidal reaction, temporary fetal akinesia, and prolonged fetal neuromuscular depression. PMID- 11770585 TI - Aggravation of the nutcracker syndrome during pregnancy. AB - BACKGROUND: The nutcracker syndrome is a rare condition thought to be caused by compression of the left renal vein between the descending aorta and the superior mesenteric artery. CASE: Gross hematuria appeared in the third trimester of an otherwise normal pregnancy. It continued despite treatment, and a cesarean was performed at 37 weeks' gestation. The hematuria stopped postpartum. With postpartum angiography and three-dimensional computed tomography, the diagnosis of nutcracker syndrome was finally made. CONCLUSION: Pregnancy can aggravate the nutcracker syndrome. This syndrome should be recognized as one of the diseases that causes gross hematuria. PMID- 11770586 TI - Angiographic embolization of a ruptured renal artery aneurysm during pregnancy. AB - BACKGROUND: Ruptured arterial aneurysms during pregnancy usually are catastrophic, and the primary approach is surgical. Angiographic embolization is an alternative treatment. CASE: A 28-year-old primigravida with a history of congenital hepatic fibrosis presented at 23 weeks' gestation with abdominal pain, hypertension, and proteinuria. She underwent a cesarean delivery for preeclampsia and a retroperitoneal hematoma was noted. A postoperative angiogram revealed bilateral renal artery and splenic aneurysms. She underwent two angiographic embolizations of a ruptured right renal artery aneurysm and was discharged to undergo outpatient embolotherapy of the left renal and splenic aneurysms. The day after discharge, she died because of rupture of the splenic aneurysm. CONCLUSION: Aggressive management of ruptured and high-risk unruptured aneurysms during pregnancy is indicated. Embolotherapy is an alternate approach if surgery is not possible. PMID- 11770587 TI - Vaginal delivery after cloacal malformation repair. AB - BACKGROUND: Patients with cloacal malformations at birth usually require multiple surgical procedures to correct their anatomic defects. Those who conceive after repairs invariably have had cesarean deliveries on the assumption that vaginal delivery would be difficult and/or dangerous. However, because they usually have undergone multiple previous abdominal procedures, cesarean delivery also may carry greater risks than in the general population. CASE: A 27-year-old nulligravida was delivered vaginally at 34 1/2 weeks' gestation, with a good maternal and neonatal outcome. CONCLUSION: Judiciously treated, pregnant patients with previously repaired cloacal malformations may be candidates for vaginal delivery. PMID- 11770588 TI - Septicemia due to multiple biotypes of Escherichia coli. AB - BACKGROUND: Polymicrobial bacteremias with different biotypes of the same organism have not been reported as a cause of bacteremia in any patient. CASE: A 37-year-old gravida had a cesarean delivery performed after a failed vacuum extraction. On the second postoperative day, she developed a septicemia with temperature to 39.4C. Three different biotypes of Escherichia coli with different antibiotic susceptibilities were isolated from her blood. A fourth biotype was isolated from the urinary and genital tracts; therefore, the source of her bacteremia was not apparent. She was treated successfully with cefoxitin and gentamicin. CONCLUSION: Accurate selection of colonies from microbiological isolation plates allowed identification of four different E. coli biotypes (three in the blood) from a bacteremic patient. Rapid identification of antibiotic susceptibility is important in such patients. PMID- 11770589 TI - Normovolemic hemodilution before cesarean hysterectomy for placenta percreta. AB - BACKGROUND: Placenta percreta can create life-threatening hemorrhage at the time of delivery. The additional challenge of patient refusal of blood transfusion for religious reasons requires the use of comprehensive blood-conserving strategies. CASE: A Jehovah's Witness with two previous cesarean deliveries and a placenta previa was diagnosed antenatally as having placenta percreta. Acute normovolemic hemodilution was performed in conjunction with cesarean hysterectomy with no maternal or fetal side effects. CONCLUSION: Acute normovolemic hemodilution can be used safely in the pregnant woman at high risk for excessive intraoperative blood loss and should be considered in obstetric patients who strictly adhere to religious convictions prohibiting the acceptance of blood products. PMID- 11770590 TI - Warfarin skin necrosis in a postpartum woman with protein S deficiency. AB - BACKGROUND: Warfarin-induced skin necrosis is a rare and dangerous complication affecting 0.01-0.1% of patients on warfarin. Deficiencies in protein C or protein S in association with other factors have been implicated in its etiology. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency. CASE: A 1-week postpartum woman with known protein S deficiency presented with skin necrosis after a previously uneventful course of warfarin. CONCLUSION: Reduced levels of free protein S during the antepartum and immediate postpartum periods predispose protein S-deficient women to warfarin skin necrosis. Previously uncomplicated courses of warfarin do not obviate the possibility of skin necrosis with future warfarin administrations. Initiation of low-dose warfarin with heparin can reduce the likelihood of this disorder. PMID- 11770591 TI - Pregnancy outcome after maternal poisoning with brodifacoum, a long-acting warfarin-like rodenticide. AB - BACKGROUND: Brodifacoum is a potent warfarin-like anticoagulant used in many rat poisoning products. Its availability has led to several reported human ingestions, none previously reported in pregnancy. CASE: A woman presented at 22 weeks' gestation in hemorrhagic diathesis, attributed to the ingestion of rat poison containing brodifacoum several days earlier. Aggressive vitamin K therapy controlled the maternal coagulopathy, and no fetal hemorrhage was observed by sonography. Her subsequent prenatal course and delivery were unremarkable, and she was delivered of a healthy infant, who has remained well for at least 1 year. CONCLUSION: In this patient, brodifacoum ingestion in pregnancy caused substantial maternal hemorrhage, but no fetal hemorrhage or teratogenic effects were observed. PMID- 11770592 TI - Poor perinatal outcome associated with maternal Brucella abortus infection. AB - BACKGROUND: Reports suggest that perinatal infection with Brucella abortus does not cause poor obstetric outcomes, because of protective mechanisms in the human, not seen in animal species. CASE: We report a case of maternal brucellosis resulting in preterm labor, chorioamnionitis, placental abruption, and delivery of a live-born infant at 25 weeks' gestational age. Both maternal blood cultures and amniotic fluid cultures were positive for B abortus species, and delivery occurred despite aggressive antibiotic and tocolytic therapy. CONCLUSION: Maternal infection with B abortus during pregnancy can lead to significant perinatal morbidity, casting doubt on reports that human pregnancy is resistant to such infection. PMID- 11770593 TI - Reversible fetal hydrops associated with indomethacin use. AB - BACKGROUND: Ductus arteriosus constriction is a known complication of exposure to indomethacin in utero. Nonimmune hydrops associated with indomethacin use has been reported in only six cases, all twins over 32 weeks' gestation. CASE: We present a case of fetal hydrops associated with tricuspid regurgitation and ductal constriction developing within 30 hours of instituting indomethacin tocolysis in a 28-week singleton gestation. Discontinuation of indomethacin resulted in partial resolution of these findings 72 hours later. A normal infant was delivered subsequently. CONCLUSION: Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age. PMID- 11770594 TI - Obstructive fetal hydronephrosis managed by amnioinfusions and bladder aspirations. AB - BACKGROUND: Fetuses diagnosed with posterior urethral valve syndrome risk development of significant pulmonary and renal complications. Historically, medical options included expectant management, percutaneous shunting, fetal surgery, and pregnancy termination. CASE: A 34-year-old primigravida presented at 26.5 weeks' gestation with severe fetal hydronephrosis. In lieu of the aforementioned options, the patient elected to undergo serial amnioinfusion and fetal bladder aspirations. The child is now 13 months old and has no evidence of pulmonary compromise but requires peritoneal dialysis. CONCLUSION: Serial amnioinfusions combined with fetal bladder aspiration may be beneficial in selected cases of severe fetal hydronephrosis. However, this case demonstrates that fetal urinary electrolytes cannot be used reliably to predict subsequent normal renal function. PMID- 11770595 TI - Doppler evidence of improved fetoplacental hemodynamics following amnioreduction in the stuck twin phenomenon. AB - BACKGROUND: Doppler ultrasound of the umbilical cord has been used to assess stuck twin pregnancies, with variable results. We describe a case of immediate improvement in the umbilical artery velocimetry of a stuck twin following amnioreduction. CASE: Pregnancy complicated by the stuck twin phenomenon was managed by serial amnioreductions. Initial improvement was followed by progressive evidence of hydrops in the smaller, stuck twin. Absent diastolic flow was corrected immediately by further amnioreduction; subsequently the evidence of hydrops resolved. CONCLUSION: Amnioreduction may be associated with a measurable improvement in fetoplacental hemodynamics in the stuck twin phenomenon as assessed by Doppler ultrasound. PMID- 11770596 TI - Elevated maternal serum alpha-fetoprotein associated with an asymptomatic tubal pregnancy at 20 weeks' gestation. AB - BACKGROUND: Most tubal ectopic pregnancies become symptomatic in the first trimester and rarely progress to the second trimester. Elevated maternal serum alpha-fetoprotein (MSAFP) has rarely been associated with second-trimester tubal pregnancy. We present a case of a 20-week asymptomatic tubal pregnancy identified by elevated MSAFP. CASE: An asymptomatic 22-year-old woman at 20 weeks' gestation was evaluated with a targeted fetal survey for an abnormally elevated MSAFP. The ultrasound examination revealed an extrauterine gestation. The patient was taken to exploratory laparotomy, and a total salpingectomy was performed. CONCLUSION: Although rare, a second-trimester ectopic pregnancy must be considered in the differential diagnosis of elevated MSAFP. A careful ultrasound scan should rule out an extrauterine pregnancy. PMID- 11770597 TI - Cornual pregnancy successfully treated laparoscopically with fibrin glue hemostasis. AB - BACKGROUND: Conventionally, cornual pregnancy has been treated by cornual resection or hysterectomy at laparotomy because it is usually hard to achieve hemostasis of the myometrial wound. We describe laparoscopic treatment with fibrin glue hemostasis in a woman with cornual pregnancy following salpingectomy. CASE: A 39-year-old woman who had a history of tubal pregnancy treated by salpingectomy presented with abdominal pain 6 weeks after her last menstrual period. Clinical and laparoscopic findings established a diagnosis of right cornual pregnancy. The products of gestation were removed laparoscopically, and the bleeding area of myometrium was first coagulated using bipolar forceps and then sealed by fibrin glue. CONCLUSION: Laparoscopy appears to be a safe alternative for patients with early cornual pregnancy, and fibrin glue is useful for achieving hemostasis of oozing myometrial wounds. PMID- 11770598 TI - Laparoscopic management of early primary abdominal pregnancy. AB - BACKGROUND: Abdominal pregnancy is a very rare condition with a high mortality rate. CASE: A 29-year-old woman with a history of primary infertility was admitted because of lower abdominal pain, bloody vaginal discharge, and positive urine pregnancy test. Transvaginal ultrasonography revealed a 27 x 25-mm mass containing a gestational sac-like structure located outside the uterus. At laparoscopy, a clot was revealed including chorionic villi, adherent to the peritoneum in the right vesicouterine pouch. This was removed along with the adherent peritoneum. Postoperative histology revealed invasion of chorionic tissues into peritoneum. CONCLUSION: Early diagnosis of an ectopic pregnancy by transvaginal ultrasonography enabled the laparoscopic management of early abdominal pregnancy. PMID- 11770599 TI - Sacral osteomyelitis: an unusual complication of abdominal sacral colpopexy. AB - BACKGROUND: Abdominal sacral colpopexy using permanent mesh is an established technique for repair of vaginal vault prolapse. Infection is not a frequent complication. We report two cases of lumbosacral osteomyelitis treated with intravenous antibiotics without mesh removal. CASES: The first patient had known advanced degenerative arthritis. Unremitting severe low back pain 5 years after abdominal sacral colpopexy prompted magnetic resonance imaging (MRI), revealing osteomyelitis and diskitis. The second patient developed symptoms 2 months postoperatively, and MRI indicated osteomyelitis with epidural abscess. Both patients received intravenous antibiotics, and neither required surgical debridement or mesh removal. CONCLUSION: Osteomyelitis can present remote from the operation and can be difficult to diagnose. Protracted parenteral antibiotic therapy can be definitive treatment without mesh removal. PMID- 11770600 TI - Combination of pessary and periurethral collagen injections for nonsurgical treatment of uterovaginal prolapse and genuine stress urinary incontinence. AB - BACKGROUND: The combination of severe uterovaginal prolapse and stress urinary incontinence in medically compromised patients in whom surgery is contraindicated is a difficult treatment dilemma. CASE: A 75-year-old woman with severe cardiac compromise and a history of pulmonary embolus presented with severe uterovaginal prolapse and stress urinary incontinence. The combination of a vaginal pessary and three periurethral collagen injections resulted in successful management of her prolapse and resolution of her stress urinary incontinence. CONCLUSION: Although pessaries are frequently a satisfactory treatment option for women with severe uterovaginal prolapse, the appearance or worsening of urinary incontinence may make the option of pessary use less attractive. The addition of periurethral collagen injections will improve or cure urinary incontinence symptoms. PMID- 11770601 TI - Prolonged urinary retention after collagen periurethral injections: a sequela of humoral immunity. AB - BACKGROUND: Approximately 3% of candidates for collagen periurethral injections are ineligible because of an immediate hypersensitivity reaction to skin testing. After a negative skin test, physicians believe patients should be free of any adverse clinical events from hypersensitivity reactions. We present a patient who developed prolonged urinary retention from a delayed hypersensitivity reaction after negative skin testing. CASE: After a negative skin test, a 51-year-old woman underwent collagen periurethral injections for recurrent genuine stress incontinence associated with a fixed bladder neck. After reporting complete resolution of symptoms, she developed complete urinary retention associated with a delayed hypersensitivity reaction at both the skin test and injection sites. Her retention resolved after a year of intermittent catheterization and antibiotics for persistent urinary tract infection. CONCLUSION: Delayed hypersensitivity reactions may be associated with an adverse clinical event in up to 2.5% of patients despite a negative skin test. After skin testing, physicians should counsel their patients accordingly. PMID- 11770602 TI - Bartholin's gland hyperplasia in a postmenopausal woman. AB - BACKGROUND: Benign solid tumors of Bartholin's gland are rare, with only six cases reported in the English language literature since 1966. Bartholin's gland hyperplasia has not been described. CASE: A postmenopausal woman with painless bilateral vulvar masses underwent surgical removal of one of the masses, which revealed a well-circumscribed, nonencapsulated tumor composed of mucous glands and ducts within a dense fibrous stroma, most consistent with hyperplasia of Bartholin's gland. CONCLUSION: Hyperplasia represents a new etiology for the enlarged Bartholin's gland. Whether the hyperplastic gland forms in response to a stimulus is unclear. However, it appears to share some features with Bartholin's gland hamartoma or adenoma. PMID- 11770603 TI - Non-Hodgkin lymphoma of the endometrium in human immunodeficiency virus infection. AB - BACKGROUND: Non-Hodgkin lymphoma has become a common malignancy in patients infected with the human immunodeficiency virus (HIV), being classified as an acquired immunodeficiency syndrome-defining malignancy. The female genital tract is involved usually with non-Hodgkin lymphoma as part of disseminated disease. It is extremely rare for this tumor to originate in the female reproductive tract, especially in the endometrium. CASE: An HIV-positive woman underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for intractable menometorrhagia and resultant anemia thought to be secondary to uterine leiomyoma. The histologic diagnosis was high-grade, immunoblastic, non-Hodgkin lymphoma with plasmacytoid features originating in the endometrium. CONCLUSION: This unusual presentation obligates the clinician to include non-Hodgkin lymphoma in the differential diagnosis when evaluating HIV-positive patients with abnormal uterine bleeding that cannot be explained after thorough evaluation. PMID- 11770604 TI - Nonfilarial chyluria during pregnancy. PMID- 11770605 TI - Self-limiting nonimmune hydrops and acute fetal small bowel distention following maternal trauma. PMID- 11770606 TI - Three-dimensional ultrasound of conjoined twins. PMID- 11770607 TI - Candida lusitaniae chorioamnionitis in a bone marrow transplant patient. PMID- 11770608 TI - Severe hyperthermia following oral misoprostol in the immediate postpartum period. PMID- 11770609 TI - Necrotizing fasciitis after delayed secondary wound closure and cesarean delivery. PMID- 11770610 TI - A retained towel associated with unusual postoperative difficulties. PMID- 11770611 TI - Cervical agenesis: septic death after surgery. PMID- 11770612 TI - Brenner tumor in 46,XY gonadal dysgenesis. PMID- 11770613 TI - Use of green fluorescent protein expressing Salmonella Stanley to investigate survival, spatial location, and control on alfalfa sprouts. AB - Laser scanning confocal microscopy (LSCM) was used to observe the interaction of Salmonella Stanley with alfalfa sprouts. The green fluorescent protein (gfp) gene was integrated into the chromosome of Salmonella Stanley for constitutive expression, thereby eliminating problems of plasmid stability and loss of signal. Alfalfa seeds were inoculated by immersion in a suspension of Salmonella Stanley (ca. 10(7) CFU/ml) for 5 min at 22 degrees C. Epifluorescence microscopy demonstrated the presence of target bacteria on the surface of sprouts. LSCM demonstrated bacteria present at a depth of 12 microm within intact sprout tissue. An initial population of ca. 10(4) CFU/g seed increased to 7.0 log CFU/g during a 24-h germination period and then decreased to 4.9 log CFU/g during a 144 h sprouting period. Populations of Salmonella Stanley on alfalfa seeds decreased from 5.2 to 4.1 log CFU/g and from 5.2 to 2.8 log CFU/g for seeds stored 60 days at 5 and 22 degrees C, respectively. The efficacy of 100, 200, 500, or 2,000 ppm chlorine in killing Salmonella Stanley associated with sprouts was determined. Treatment of sprouts in 2,000 ppm chlorine for 2 or 5 min caused a significant reduction in populations of Salmonella Stanley. Influence of storage on Salmonella Stanley populations was investigated by storing sprouts 4 days at 4 degrees C. The initial population (7.76 log CFU/g) of Salmonella Stanley on mature sprouts decreased (7.67 log CFU/g) only slightly. Cross-contamination during harvest was investigated by harvesting contaminated sprouts, then directly harvesting noncontaminated sprouts. This process resulted in the transfer of ca. 10(5) CFU/g Salmonella Stanley to the noncontaminated sprouts. PMID- 11770614 TI - Ecological relationships between the prevalence of cattle shedding Escherichia coli O157:H7 and characteristics of the cattle or conditions of the feedlot pen. AB - This study was designed to describe the percentage of cattle shedding Escherichia coli O157:H7 in Midwestern U.S. feedlots and to discover relationships between the point prevalence of cattle shedding the organism and the characteristics of those cattle or the conditions of their pens. Cattle from 29 pens of five Midwestern feedlots were each sampled once between June and September 1999. Feces were collected from the rectum of each animal in each pen. Concurrently, samples of water were collected from the water tank, and partially consumed feed was collected from the feedbunk of each pen. Characteristics of the cattle and conditions of each pen that might have affected the prevalence of cattle shedding E. coli O157:H7 were recorded. These factors included the number of cattle; the number of days on feed; and the average body weight, class, and sex of the cattle. In addition, the temperature and pH of the tank water were determined, and the cleanliness of the tank water and the condition of the pen floor were subjectively assessed. The samples of feces, feed, and water were tested for the presence of E. coli O157:H7. E. coli O157:H7 was isolated from the feces of 719 of 3,162 cattle tested (23%), including at least one animal from each of the 29 pens. The percentage of cattle in a pen shedding E. coli O157:H7 did not differ between feedyards, but it did vary widely within feedyards. A higher prevalence of cattle shed E. coli O157:H7 from muddy pen conditions than cattle from pens in normal condition. The results of this study suggest that E. coli O157:H7 should be considered common to groups of feedlot cattle housed together in pens and that the condition of the pen floor may influence the prevalence of cattle shedding the organism. PMID- 11770615 TI - Phenotypic and genotypic characterization of Escherichia coli verotoxin-producing isolates from humans and pigs. AB - The aim of this study was to characterize verotoxin-producing Escherichia coli (VTEC) isolates obtained from humans and pigs in the same geographic areas and during the same period of time in order to determine whether porcine VTEC isolates could be related to human cases of diarrhea and also to detect the presence of virulence factors in these isolates. From 1,352 human and 620 porcine fecal samples, 11 human and 18 porcine verotoxin-positive isolates were obtained by the VT immunoblot or the individual colony testing technique. In addition, 52 porcine VTEC strains isolated from diseased pigs at the Faculte de medecine veterinaire during the same period or from fecal samples collected previously isolated at slaughterhouses were characterized in this study. Antimicrobial resistance profiles were different between human and porcine isolates. In general, the serotypes observed in the two groups were different. No porcine isolate was of serotype O157:H7; however, one isolate was O91:NM, a serotype that has been associated with hemorrhagic colitis in humans. Also, one serotype (O8:H19) was found in isolates from both species; however, the O8:H19 isolates of the two groups were of different pathotypes. The pathotypes observed in the human and porcine isolates were different, with the exception of VT2vx-positive isolates; the serotypes of these isolates from the two groups were nevertheless different. Pulsed-field gel electrophoresis analysis indicated no relatedness between the human and porcine isolates. In conclusion, these results suggest that the porcine and human isolates of the present study were not genetically related. Most porcine VTEC isolates did not possess known virulence factors required to infect humans. However, certain non-O157:H7 porcine VTECs may potentially infect humans. PMID- 11770616 TI - Monitoring of chicken houses and an attached egg-processing facility in a laying farm for Salmonella contamination between 1994 and 1998. AB - Two chicken houses and an attached egg-processing facility in a laying farm were sampled between 1994 and 1998 to investigate Salmonella contamination. Each of the houses was environmentally controlled and fitted with egg belts that transported eggs from the houses to the egg-processing facility. Four hundred twenty-eight Salmonella isolates were obtained from 904 environmental samples collected from the houses. Two hundred fifty-two of the 428 (58.9%) isolates yielded five serotypes as follows: Salmonella enterica subsp. enterica serovar Livingstone, Salmonella serovar Cerro, Salmonella serovar Montevideo, Salmonella serovar Mbandaka, and Salmonella serovar Corvallis. The remaining (41.1%, 176 of 428) isolates included four other serotypes and isolates that were untypeable. Salmonella isolates obtained from the drain water collected after the washing of the eggs in the egg-processing facility yielded the same serotypes as those found in the chicken houses. Strains having an identical pulsed-field gel electrophoresis (PFGE) pattern were continually recovered from a house for more than 1 year. Several strains of Salmonella Cerro, Salmonella Mbandaka, and Salmonella Montevideo obtained from both the houses and from the egg-processing facility were indistinguishable by PFGE, respectively. These results suggest that Salmonella organisms originating from a single clone colonized the chicken houses and that the egg belts are likely to be one of the means by which Salmonella organisms are spread from one house to the others. PMID- 11770617 TI - Comparison of Salmonella Enteritidis infection in hens molted via long-term feed withdrawal versus full-fed wheat middling. AB - Molting is an important economic management tool for the layer industry as a means of maximizing the effective laying life of a flock. Previous work has shown that molting birds through feed removal (FM) increased the severity of a Salmonella Enteritidis (SE) infection. The current study was conducted to follow the progression of an SE infection in unmolted hens versus hens molted via 14-day FM or ad libitum feeding of wheat middlings (WM), in the presence or absence of 2.5% lactose administered in the drinking water. In two trials of the experiment, all hens were infected with approximately 1 x 10(7) SE at day 4 of molt and sampled for SE shedding on days 4, 10, 17, and 24 postinfection (PI). Organ levels of SE were determined on day 7 PI. All molt procedures caused cessation of egg lay within 3 to 7 days. In trials 1 and 2, birds subjected to total FM shed 3 to 5 logs more SE than either the control birds (unmolted) or the birds fed WM on days 4 and 10 PI. Liver and spleen, ovary, and cecum counts were also significantly (P < 0.05) higher in the fasted birds in one trial and liver and spleen and cecum counts in the second. No differences in any of the SE counts were observed in unmolted versus WM-fed birds. Lactose supplementation in drinking water did not provide any advantage in reducing SE infection in either trial. These results indicate that there are alternative methods to long-term FM that can be used to molt birds and not increase the risk for SE problems. How these alternative methods compare with FM with regard to second-cycle egg production and the mechanisms involved in the reduced SE shedding remain to be investigated. PMID- 11770618 TI - A probability of growth model for Escherichia coli O157:H7 as a function of temperature, pH, acetic acid, and salt. AB - Data accumulated on the growth of Escherichia coli O157:H7 in tryptic soy broth (TSB) were used to develop a logistic regression model describing the growth-no growth interface as a function of temperature, pH, salt, sucrose, and acetic acid. A fractional factorial design with five factors was used at the following levels: temperature (10 to 30 degrees C), acetic acid (0 to 4%), salt (0.5 to 16.5%), sucrose (0 to 8%), and pH (3.5 to 6.0). A total of 1,820 treatment combinations were used to create the model, which correctly predicted 1,802 (99%) of the points, with 10 false positives and 8 false negatives. Concordance was 99.9%, discordance was 0.1%, and the maximum rescaled R2 value was 0.927. Acetic acid was the factor having the most influence on the growth-no growth interface; addition of as little as 0.5% resulted in an increase in the observed minimum pH for growth from 4.0 to 5.5. Increasing the salt concentration also had a significant effect on the interface; at all acetic acid concentrations, increasing salt increased the minimum temperature at which growth was observed. Using two literature data sets (26 conditions), the logistic model failed to predict growth in only one case. The results of this study suggest that the logistic regression model can be used to make conservative predictions of the growth-no growth interface of E. coli O157:H7. PMID- 11770619 TI - Inactivation of Escherichia coli O157: H7 and Listeria monocytogenes by PR-26, a synthetic antibacterial peptide. AB - This study reports the antibacterial effect of PR-26, a synthetic peptide derived from the first 26 amino acid sequence of PR-39, an antimicrobial peptide isolated from porcine neutrophils. A three-strain mixture of Escherichia coli O157:H7 or Listeria monocytogenes of approximately 10(8) CFU was inoculated to a final concentration of 10(7) CFU/ml in 1% peptone water (pH 7.0), containing 50 or 75 microg/ml of PR-26, and incubated at 37 degrees C for 0, 6, 12, and 24 h; at 24 degrees C for 0, 12, 24, and 36 h; or at 10 or 4 degrees C for 0, 24, 72, and 120 h. Control samples included 1% peptone water inoculated with each pathogen mixture but containing no PR-26. The surviving population of each pathogen at each sampling time was determined by plating on tryptic soy agar with incubation at 37 degrees C for 24 h. At 37 degrees C, PR-26 decreased E. coli O157:H7 and L. monocytogenes populations by >5.0 log CFU/ml at 12 h, with complete inactivation at 24 h. At 24 degrees C, PR-26 reduced E. coli O157:H7 and L. monocytogenes by approximately 3.5, 4.0, and 4.5 log CFU/ml at the end of 12-, 24-, and 36-h incubations, respectively. At 4 and 10 degrees C, the inhibitory effect of PR-26 on E. coli O157:H7 and L. monocytogenes was significantly lower (P < 0.05) than that at 37 and 24 degrees C: a 2- to 3-log CFU/ml reduction was observed at 120-h incubation. Results indicate that PR-26 could potentially be used as an antimicrobial agent, but applications in appropriate foods need to be validated. PMID- 11770620 TI - Prediction of microbial growth in fresh-cut vegetables treated with acidic electrolyzed water during storage under various temperature conditions. AB - Effects of storage temperature (1, 5, and 10 degrees C) on growth of microbial populations (total aerobic bacteria, coliform bacteria, Bacillus cereus, and psychrotrophic bacteria) on acidic electrolyzed water (AcEW)-treated fresh-cut lettuce and cabbage were determined. A modified Gompertz function was used to describe the kinetics of microbial growth. Growth data were analyzed using regression analysis to generate "best-fit" modified Gompertz equations, which were subsequently used to calculate lag time, exponential growth rate, and generation time. The data indicated that the growth kinetics of each bacterium were dependent on storage temperature, except at 1 degrees C storage. At 1 degrees C storage, no increases were observed in bacterial populations. Treatment of vegetables with AcEW produced a decrease in initial microbial populations. However, subsequent growth rates were higher than on nontreated vegetables. The recovery time required by the reduced microbial population to reach the initial (treated with tap water [TW]) population was also determined in this study, with the recovery time of the microbial population at 10 degrees C being <3 days. The benefits of reducing the initial microbial populations on fresh-cut vegetables were greatly affected by storage temperature. Results from this study could be used to predict microbial quality of fresh-cut lettuce and cabbage throughout their distribution. PMID- 11770621 TI - Joint effect of nisin, CO2, and EDTA on the survival of Pseudomonas aeruginosa and Enterococcus faecium in a food model system. AB - A study on the joint effect of either nisin or Nisaplin, headspace CO2 levels, and EDTA on the survival of Pseudomonas aeruginosa and Enterococcus faecium was carried out in a water-soluble fish muscle extract at 3 degrees C using a second order rotatable factorial design. E. faecium was completely deactivated by all processing after 2 days of storage. In contrast, P. aeruginosa was much less susceptible to treatments, and cell death was satisfactorily described by two models. Nisin increased cell death, whereas Nisaplin (commercial form of nisin) was not suitable, as it caused undesirable interference, presumably due to its co compounds. Interactions between Nisaplin or nisin and either EDTA or CO2 were found to be nonstatistically significant. Factors that could account for this unexpected lack of synergism are discussed. However, a statistically significant positive interaction was found between CO2 and EDTA. This finding could allow CO2 levels to be decreased and hence to reduce the main disadvantages of CO2 application, namely, exudation and acidification. PMID- 11770622 TI - Antimicrobials in the formulation to control Listeria monocytogenes postprocessing contamination on frankfurters stored at 4 degrees C in vacuum packages. AB - Postprocessing contamination of cured meat products with Listeria monocytogenes during slicing and packaging is difficult to avoid, and thus, hurdles are needed to control growth of the pathogen during product storage. This study evaluated the influence of antimicrobials, included in frankfurter formulations, on L. monocytogenes populations during refrigerated (4 degrees C) storage of product inoculated (10(3) to 10(4) CFU/cm2) after peeling of casings and before vacuum packaging. Frankfurters were prepared to contain (wt/wt) sodium lactate (3 or 6%, as pure substance of a liquid, 60% wt/wt, commercial product), sodium acetate (0.25 or 0.5%), or sodium diacetate (0.25 or 0.5%). L. monocytogenes populations (PALCAM agar and Trypticase soy agar plus 0.6% yeast extract [TSAYE]) exceeded 10(6) CFU/cm2 in inoculated controls at 20 days of storage. Sodium lactate at 6% and sodium diacetate at 0.5% were bacteriostatic, or even bactericidal, throughout storage (120 days). At 3%, sodium lactate prevented pathogen growth for at least 70 days, while, in decreasing order of effectiveness, sodium diacetate at 0.25% and sodium acetate at 0.5 and 0.25% inhibited growth for 20 to 50 days. Antimicrobials had no effect on product pH, except for sodium diacetate at 0.5%, which reduced the initial pH by approximately 0.4 U. These results indicate that concentrations of sodium acetate currently permitted by the U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS) (0.25%) or higher (0.5%) may control growth of L. monocytogenes for approximately 30 days, while currently permitted levels of sodium lactate (3%) and sodium diacetate (0.25%) may be inhibitory for 70 and 35 to 50 days, respectively. Moreover, levels of sodium lactate (6%) or sodium diacetate (0.5%) higher than those presently permitted by the USDA-FSIS may provide complete control at 4 degrees C of growth (120 days) of L. monocytogenes introduced on the surface of frankfurters during product packaging. PMID- 11770623 TI - Occurrence of Clostridium perfringens in the broiler chicken processing plant as determined by recovery in iron milk medium. AB - Over 30 years ago, Clostridium perfringens was reported as a contaminant of the processing plant and processed carcasses of broiler chickens. Poultry processing procedures and methods for detecting C. perfringens have changed since that time. Therefore, a study was conducted to determine the incidence and numbers of C. perfringens in the water of the scald tank, the water of the chill tank, and the rinse water of the processed carcasses from modern broiler chicken processing plants. In trial 1, collected samples were inoculated into iron milk medium (IMM) and incubated at 46 degrees C for 18 h (the traditional method) or at 37 degrees C for 3 h followed by incubation at 46 degrees C for 15 h (an injury recovery method). Each of three preselected broiler chicken flocks from two integrators were the first processed for that processing shift. The overall incidence of confirmed C. perfringens in samples associated with the three flocks was 40% of postprocessing scald water samples, 13% of preprocessing chill water samples, 13% of postprocessing chill water samples, and 19% of carcass rinses. The incidence of C. perfringens in samples incubated in IMM using the injury recovery procedure was significantly higher than in samples incubated in IMM by the traditional method, but only when all samples associated with the three flocks were pooled. In trial 2, water samples from each tank of a three-tank counterflow scalder, water samples from the prechill and chill tank, and samples of carcass rinses were collected in the middle of a processing shift during multiple visits to a processing plant. Samples were inoculated into IMM with neomycin and polymyxin B sulfate (IMMA) and incubated using the traditional and injury recovery procedures. The incidence of C. perfringens in water samples was 100% from scald tank 1, 100% from scald tank 2, 100% from scald tank 3, 88% from the prechill tank, and 63% from the chill tank. The incidence in carcass rinse samples was 67%. The mean most probably number (MPN) of C. perfringens for contaminated samples decreased from log10 5.07/100 ml of water in scald tank 1 to log10 1.26/100 ml of water in the chill tank. The mean MPN in carcass rinse samples was log10 1.20 C. perfringens per 100 ml. The incidence and mean MPN of C. perfringens in these samples after heat shock at 75 degrees C for 20 min was somewhat less, but high enough to indicate that much of the contamination arises from heat-resistant spores of this organism. In trial 2, there were no differences in incidence and MPN of C. perfringens in samples incubated in IMMA with the traditional method or the injury recovery method. PMID- 11770624 TI - Microbiological quality of retail poultry carcasses in Spain. AB - A total of 40 eviscerated and refrigerated chicken carcasses were collected from five retail outlets (three supermarkets and two poulterers' shops) in Leon (Spain). The level of microorganisms on chicken carcasses was assessed using the excised breast-skin technique. Mean counts (log10 CFU/g) of psychrotrophs, pseudomonads, fluorescent pseudomonads, enterococci, Micrococcaceae, Staphylococcus aureus, and yeasts and molds were 4.84, 4.11, 3.32, 2.72, 3.80, 3.67, and 2.99, respectively. A significant correlation coefficient was found between pseudomonads and fluorescent pseudomonad counts (r = 0.827; P < 0.001) and between Micrococcaceae and S. aureus counts (r = 0.915; P < 0.001). Levels of psychrotrophs, pseudomonads, fluorescent pseudomonads, and yeasts and molds were significantly (P < 0.05) higher in supermarkets than in poulterers' shops, possibly due to the longer period of time the carcasses spent in the supermarkets (between 1 and 2 days, as opposed to only 4 to 16 h in the case of poulterers' shops). Carcasses from poulterers' shops showed higher (P < 0.05) counts of enterococci. Micrococcaceae, and S. aureus, which suggests higher storage temperatures in these outlets. Only S. aureus counts (especially those from poulterers' shops) exceeded the established values in the microbiological criteria for poultry meat consulted. PMID- 11770625 TI - Pork producers' attitudes, knowledge, and production practices that relate to on farm food safety. AB - A survey was distributed by mail to a random selection of Illinois pig farmers marketing 1,000 or more pigs in 1998 to assess their knowledge, attitude and behavior regarding on-farm food safety. Valid responses were received from 353 of the 946 surveys mailed (37.3%). Pork production accounted for more than 50% of gross agricultural revenues among 65.0% of respondents, and 91.2% were classified as "owner-operators." Knowledge of food-borne pathogens was mixed, with correct responses to questions as follows: Trichina, 80.4%; Salmonella, 58.5%; Toxoplasma, 19.9%; and Campylobacter, 12.8%. Producers strongly agreed that food safety was a shared responsibility at every level of the food chain, including the farm level, with an average score for all steps in the pork chain of 4.5 on a scale from 1 (not important) to 5 (very important). When asked whether third party verification of on-farm practices was important, 51.2% agreed and 48.8% either disagreed or neither agreed nor disagreed. Associations between demographic categories and knowledge of and attitudes toward food safety were detected for herd size, proportion of agricultural receipts from pig production, grower versus birth-to-market production, age categories, and whether the respondent owned the pigs or facilities. Many (53.4%) were willing to apply a suggested food safety practice, even if there was no net profit for the practice. Findings suggest that Illinois pork producers accept an important role in pork food safety and express a willingness to participate but have knowledge gaps that should be filled. PMID- 11770626 TI - Classification of grossly detectable abnormalities and conditions seen at postmortem in Canadian poultry abattoirs according to a hazard identification decision tree. AB - This study was designed to review all grossly detectable abnormalities and conditions (GDACs) encountered in poultry in Canadian abattoirs to determine which have potential to cause adverse health effects for the consumer. Review of the literature and consultation with scientists in the field of microbiology, epidemiology, poultry pathology, chemistry, and meat inspection served to generate an inventory of GDACs, and a decision tree containing algorithms was developed to identify GDACs potentially representing a health hazard to consumers. Through the use of the decision tree, GDACs were classified into different categories with regard to the risk they represent to humans. A number of GDACs were identified as being of potential concern from a food safety perspective, namely Erysipelas, fowl cholera, Campylobacteriosis, clostridial diseases, hepatitis/enteritis associated with Helicobacter, Listeriosis, Salmonella infections (nontyphoid infections, Salmonella arizonae, pullorum disease, and fowl typhoid), Staphylococcosis, and Toxoplasmosis. Further characterization--i.e., hazard characterization, exposure assessment, and risk characterization--is required to quantify or better characterize the probability that products derived from affected carcasses may affect the consumer as well as the resulting consequences. Risk assessment is a dynamic process. Results presented in this paper are based on available information and expert opinion. As new information is obtained, the inventory of GDACs and their classification may be modified. PMID- 11770627 TI - Microbial and quality attributes of ground pork prepared from commercial pork trim treated with combination intervention processes. AB - The effects of combination intervention treatments of commercial pork trim on microbial and quality attributes of the subsequent ground pork were examined. Fresh commercial pork trim was inoculated with swine feces and subjected to five different intervention treatments: (i) control (untreated), (ii) water (15 degrees C, 120 s), (iii) water followed by 2% lactic acid wash (15 degrees C, 75 s), (iv) Combination 1 (water plus lactic acid plus hot air [510 degrees C, 90 s]), and (v) Combination 2 (hot air plus water plus hot air). Following treatment, the pork trim was stored at 4 degrees C for 24 h, then ground, stuffed, vacuum packaged, and stored at 4 degrees C for 21 days. Populations of aerobic bacteria, coliforms, Escherichia coli, and lactic acid bacteria in the ground pork were monitored before treatment, after treatment (day 0), and at 2, 7, 14 and 21 days. In addition, uninoculated pork trim was treated as described above, and the color and emulsion stability of the ground product was evaluated. Ground pork prepared from trim treated with any of the treatment processes had lower initial microbial populations compared to the untreated samples. The applications of water plus lactic acid or Combination 1, which included a lactic acid wash, were more effective than water or Combination 2 at both reducing initial populations and suppressing the growth of aerobic bacteria, coliforms, and E. coli in ground pork during refrigerated storage. By day 21, populations of aerobic bacteria in ground pork prepared from control, water-treated, and Combination 2-treated trim were 8.22 to 8.32 log CFU/g, but in water plus lactic acid and Combination 1 ground pork, populations were 6.32 and 4.90 log CFU/g, respectively. Among the trim interventions examined, Combination 1 was most detrimental to the color and emulsion stability of the ground pork. The water plus lactic acid treatment provided the greatest microbial reduction and inhibition without large negative effects on quality attributes of the ground pork. PMID- 11770628 TI - Alfalfa seed germination and yield ratio and alfalfa sprout microbial keeping quality following irradiation of seeds and sprouts. AB - Foods can be treated with gamma radiation, a nonthermal food process, to inactivate foodborne pathogens and fungi, to kill insects on or in fruits and vegetables, and to increase shelf life. Gamma irradiation is especially well suited for these treatments because of its ability to penetrate commercial pallets of foods. Irradiated fruits, vegetables, poultry, and hamburger have been received favorably by the public and are now available in supermarkets. The use of irradiation on fresh alfalfa sprouts was studied to determine its effect on keeping quality as related to aerobic microbial load. After an irradiation dose of 2 kGy, the total aerobic count decreased from 10(5-8) to 10(3-5) CFU/g, and the total coliform counts decreased from 10(5-8) to 10(3-0) CFU/g. The results showed that the sprouts maintained their structure after irradiation, and the keeping quality was extended to 21 days, which is an increase of 10 days from the usual shelf life. The effect of various doses of irradiation on alfalfa seeds as measured by percent germination and yield ratio (wt/wt) of sprouts was determined. There was little effect on the percent germination, but as the dose increased, the yield ratio of alfalfa sprouts decreased. As the length of growing time increased, so did the yield ratio of the lower dose irradiated seeds (1 to 2 kGy). The irradiation process can be used to increase the shelf life of alfalfa sprouts, and irradiating alfalfa seeds at doses up to 2 kGy does not unacceptably decrease the yield ratio for production of alfalfa sprouts. PMID- 11770629 TI - Simple tests for rapid assessment of the quality of raw milk. AB - Simple and inexpensive tests are described for rapid qualitative assessment of the microbiological quality of raw milk. These tests included the monitoring of dissolved oxygen levels and changes in the color of raw milk with time in a slightly modified methylene blue test using 16 ppm of dye concentration. The initial bacterial population in raw milk determined by standard plate count could be estimated with coefficients of determination (r2) of about 0.697 and 0.613 from the respective normalized voltage outputs of the dissolved oxygen probe and light-sensing probes at selected time intervals in less than 1 h. However, a comparison of experimental and estimated initial bacterial populations in raw milk showed correlation coefficients (r) of about 0.754 and 0.616 for the dissolved oxygen probe and light-sensing probe, respectively. These results clearly indicated the potential and need for improving such empirical models for grading raw milk with both types of probes. PMID- 11770630 TI - Enzyme-based most probable number method for the enumeration of Bifidobacterium in dairy products. AB - An enzyme-based assay in combination with the most probable number (MPN) technique was developed for the enumeration of bifidobacteria. The assay employs the detection of fructose-6-phosphate phosphoketolase (F6PPK) activity as an indicator of the presence of bifidobacteria. The method was validated against viable counts and optimized with respect to selective media in order to quantitatively assess bifidobacteria in dairy products and other probiotic preparations. Several commercial products and homemade fermented milks were analyzed. Counts of bifidobacteria ranged from 10(7) to 10(8) MPN/ml in commercial products and homemade fermented milks. Commercial starters provided by Argentinean industries had between 10(7) and 10(11) MPN/ml. The results obtained in this study suggest that the combination of F6PPK activity determination and the MPN methodology allows an accurate determination of Bifidobacterium in pure cultures, dairy products, and other probiotic preparations. PMID- 11770631 TI - Gradient diffusion antibiotic susceptibility testing of potentially probiotic lactobacilli. AB - Minimum inhibitory contentrations (MICs) of selected inhibitors of cell wall synthesis (benzylpenicillin, ampicillin, and vancomycin), protein synthesis (gentamicin, streptomycin, tetracycline, chloramphenicol, and erythromycin), and nucleic acid synthesis (co-trimoxazole, rifampicin, and metronidazole) were determined by gradient diffusion (E test; AB Biodisk, Solna, Sweden) on deMan, Rogosa, Sharpe (MRS) agar for Lactobacillus strain GG and 11 closely related, rapidly growing, facultatively anaerobic, potentially probiotic Lactobacillus rhamnosus strains. All strains were resistant to vancomycin (MIC90 > or = 256 microg/ml), co-trimoxazole (MIC90 > or = 32 microg/ml), metronidazole (MIC90 > or = 32 microg/ml), gentamicin (MIC90 > or = 128 microg/ml), and streptomycin (MIC90 > or = 256 microg/ml), and sensitive to pencillin G (MIC90 > 0.375 microg/ml), ampicillin (MIC90 > 0.750 microg/ml), rifampicin (MIC90 > 0.375 microg/ml), tetracycline (MIC90 > 1.5 microg/ml), chloramphenicol (MIC90 > 8 microg/ml), and erythromycin (MIC90 > 2 microg/ml). E test MICs were also determined for L. acidophilus National Collection of Food Bacteria (NCFB) 1748 and L. reuteri Deutsche Sammlung von Mikroorganismen 20016T by the inoculum application method recommended by the manufacturer (swabbing), with and without antibiotic prediffusion for 1 h at room temperature, and by an alternative inoculum application (agar overlay) method, without antibiotic prediffusion. Antibiotic prediffusion increased the MICs for penicillin G, ampicillin, tetracycline, and chloramphenicol by up to 2 log2 MIC dilutions without changing antibiotic susceptibility category. Agar overlay application also increased the MICs for these antibiotics as well as for gentamicin by up to 3 log2 MIC dilutions without changing antibiotic susceptibility category. Exact agreement between MICs determined by swab and agar overlay application without antibiotic prediffusion was strain dependent: 54.5% for strain DSM 20016T and 72.7% for strain NCFB 1748. The swab and agar overlay gradient diffusion methods provide a reliable basis for antibiotic susceptibility testing of rapidly growing, facultatively anaerobic lactobacilli, using MRS agar as test medium and are readily applicable for testing individual isolates as needed. PMID- 11770632 TI - Growth and histamine formation of Morganella morganii in determining the safety and quality of inoculated and uninoculated bluefish (Pomatomus saltatrix). AB - The objective of this study was to determine the effect of normal microflora and Morganella morganii on histamine formation and olfactory acceptability in raw bluefish under controlled storage conditions. Fillets inoculated with and without M. morganii were stored at 5, 10, and 15 degrees C for 7 days. Microbial isolates from surface swabs were identified and screened for histidine decarboxylase activity. Olfactory acceptance was performed by an informal sensory panel. Histamine levels were quantified using high-performance liquid chromatography and fluorescence detection. While olfactory acceptance decreased, histamine concentration and bacterial counts increased. Storage temperature had a significant effect on histamine levels, bacterial counts, and olfactory acceptance of the bluefish. Inoculation with M. morganii had a positive significant effect on histamine formation for bluefish held at 10 and 15 degrees C (P < 0.0001). The results of the study will serve in supporting U.S. Food and Drug Administration (FDA) regulations regarding guidance and hazard levels of histamine in fresh bluefish. PMID- 11770633 TI - Consumer acceptance of irradiated meat and poultry in the United States. AB - Food manufacturers in the United States are currently allowed to irradiate raw meat and poultry to control microbial pathogens and began marketing irradiated beef products in mid-2000. Consumers can reduce their risk of foodborne illness by substituting irradiated meat and poultry for nonirradiated products, particularly if they are more susceptible to foodborne illness. The objective of this study was to identify the individual characteristics associated with willingness to buy irradiated meat and poultry, with a focus on five risk factors for foodborne illness: unsafe food handling and consumption behavior, young and old age, and compromised immune status. A logistic regression model of willingness to buy irradiated meat or poultry was estimated using data from the 1998-1999 FoodNet Population Survey, a single-stage random-digit dialing telephone survey conducted in seven sites covering 11% of the U.S. population. Nearly one-half (49.8%) of the 10,780 adult respondents were willing to buy irradiated meat or poultry. After adjusting for other factors, consumer acceptance of these products was associated with male gender, greater education, higher household income, food irradiation knowledge, household exposure to raw meat and poultry, consumption of animal flesh, and geographic location. However, there was no difference in consumer acceptance by any of the foodborne illness risk factors. It is unclear why persons at increased risk of foodborne illness were not more willing to buy irradiated products, which could reduce the hazards they faced from handling or undercooking raw meat or poultry contaminated by microbial pathogens. PMID- 11770634 TI - Microbiological, sensory, and electronic nose evaluation of yellowfin tuna under various storage conditions. AB - Microbiological assessment, sensory evaluation, and electronic nose (AromaScan) analysis were performed on yellowfin tuna stored at 0, 4, 10, and 22 degrees C for 0, 1, 3, 5, and 9 days. Fish color, texture, appearance, and odor were evaluated by a trained sensory panel, while aroma-odor properties were evaluated using an AromaScan. Bacterial enumeration was performed using plate count agar containing 1.5% NaCl. Tuna fillets stored at 22 degrees C for 3 days or longer had a bacterial load of over 10(7) CFU/g and were rated not acceptable for consumption (grade C) by the sensory panel. Tuna fillets stored at 4 degrees C for 9 days or 10 degrees C for over 5 days were rated as grade C products and also had a bacterial load of over 10(7) CFU/g. The change in fish quality as determined by AromaScan followed increases in microbiological counts in tuna fillets, indicating that bacterial load can serve as a useful and objective indicator of gross spoilage. Electronic nose devices can be used in conjunction with microbial counts and sensory panels to evaluate the degree of decomposition in tuna during storage. PMID- 11770635 TI - Evaluation of the antioxidant properties of Mediterranean and tropical fruits compared with common food additives. AB - Several Mediterranean and tropical fruits have been analyzed in order to assess their antioxidant activity compared with that of common food additives (butylated hydroxyanisole [BHA], butylated hydroxytoluene [BHT] and propyl gallate). Among Mediterranean fruits, red grape and plum were more effective (P < 0.05) scavengers of peroxyl radicals than BHA, BHT, and propyl gallate. Of the tropical fruits, banana was the most effective scavenger of peroxyl radicals. Mediterranean and tropical fruits showed very good scavenger activity against hydroxy radicals (OH*), protecting deoxyribose better than BHA and BHT. The HOCI scavenging ability of Mediterranean fruits tested was, in decreasing order, lemon > plum > apricot > white grape > melon > red grape > mandarin > watermelon > peach > medlar > apple > orange > cherry > strawberry. However, the four varieties of pear were poor scavengers (P < 0.05). Among tropical fruits, the order of efficiency as HOCI scavengers was passion fruit > lime > passiflora > kumquat > avocado > pineapple > physalis > papaya fruit > carambola > mango > banana. All Mediterranean fruits showed an effect on hydrogen peroxide except peach. Tropical fruits also had a strong effect on hydrogen peroxide except avocado, which had no effect. The effect of Mediterranean and tropical fruits on the protection factor of refined olive oil, analyzed by the Rancimat method and compared with common food additives, was clear. Watermelon conferred a significantly (P < 0.05) greater protection than the other Mediterranean fruits. Among tropical fruits, physalis had the most stabilizing effect. PMID- 11770636 TI - The detection of central nervous system tissue on beef carcasses and in comminuted beef. AB - We report the development and validation of a fluorescent enzyme-linked immunosorbent assay (ELISA) for glial fibrillary acidic protein (GFAP), which can be used as a rapid and sensitive method to detect CNS tissue in meat products. The fluorometric assay is sensitive to 0.2 ng GFAP and has an intra-assay coefficient of variation (CV) of 2.0% and an interassay CV of 14.1%. Bovine spinal cord and brain demonstrate dose-response curves that are parallel to GFAP standards, whereas peripheral sciatic nerve and cervical ganglia also cross-react at high tissue levels. The use of another central nervous system marker, syntaxin 1-B, was not effective for neural tissue detection. Less than 1.0 ng GFAP per mg tissue was found on most beef subprimals and advanced meat recovery (AMR) product. Occasional samples contained higher levels of GFAP, probably because of contamination by the carcass-splitting saw, incomplete removal of the spinal cord, or a chance sampling of a major nerve. Further reduction of CNS content was facilitated by removal of the cervical vertebrae and the spinal canal prior to processing beef chuck bones through AMR equipment. The presence of GFAP was very low (0.037 ng/mg) in beef patties collected from major processors throughout the USA. The presence of normal sausage ingredients or heating the product to 80 degrees C for 60 min did not affect the detection of GFAP. Heating the product to 115 degrees C for 100 min eliminated the detectability of GFAP. PMID- 11770637 TI - Fate of salmonellae in calcium-supplemented orange juice at refrigeration temperature. AB - Recent outbreaks of salmonellosis associated with orange juice have raised interest concerning the survival and growth of Salmonella in juice supplemented with calcium. A study was done to determine the influence of various calcium supplements on the survival of salmonellae in orange juice held at 4 degrees C for up to 32 days. Isolates of Salmonellal Muenchen (inoculum 1), Salmonella isolates from humans and animals (inoculum 2), and Salmonella isolates from produce outbreaks (inoculum 3) were inoculated into pasteurized orange juices with pH values ranging from 3.96 to 4.19 and containing 350 mg of calcium per 240 ml serving (1.46 mg of calcium/ml). Populations of Salmonella declined rapidly in juice containing calcium lactate (CaL), with counts decreasing from 4.86 log10 CFU/ml to < 1 log10 CFU/ml within 16 days, regardless of the Salmonella serotypes present in inoculum. Counts decreased from 4.89 log10 CFU/ml to < 1 log10 CFU/ml in orange juice supplemented with CaL and tricalcium phosphate (TCP) within 30 days. These reductions were significantly (P < or = 0.05) higher than those of the control (no calcium added), in which Salmonella populations decreased 3.19 +/ 0.20 log10 CFU/ml over 32 days. Populations in orange juice containing TCP or calcium citrate (CC) declined 1.34 +/- 0.20 log10 CFU/ml and 1.96 +/- 0.20 log10 CFU/ml, respectively, over 32 days. These counts were significantly higher than respective control counts in juice stored for 32 days. Populations of Salmonella of inoculum 3 inoculated into juice containing calcium citrate malate (CCM) were significantly higher than in the control. Higher numbers of cells in inoculum 3 also survived compared to numbers of cells of inocula 1 or 2 in juice supplemented with CCM. This study reveals that the form of calcium used to supplement orange juice influences the ability of salmonellae to survive. PMID- 11770638 TI - Use of luminescent Campylobacter jejuni ATCC 33291 to assess eggshell colonization and penetration in fresh and retail eggs. AB - A luminescent phenotype in Campylobacter jejuni ATCC 33291, generated by a transcriptional fusion between the C. jejuni flaA sigma28 promoter and the luxCDABE genes of Xenorhabdus luminescens on plasmid pRYluxCDABE, was used to examine colonization and penetration of fresh and retail eggs. C. jejuni colonized both fresh and retail eggs at 37, 40, and 42 degrees under microaerophilic conditions. Fresh eggs were more heavily colonized than retail eggs. Under aerobic conditions, fresh eggs were colonized at similar levels for all three temperatures. C. jejuni was found to penetrate the eggshell in 2 of 48 (4.2%) fresh eggs assessed. Although the lux+ phenotype did not provide an effective means of predicting penetration sites, it was effective at visualizing eggshell colonization. Also, it effectively demonstrated the organism's opportunistic nature, as eggshell surfaces with flaws and slight cracks were extensively colonized and easily detected by a photon counting charge-coupled device camera. Using scanning electron microscopy, C. jejuni ATCC 33291 was visualized on both the exterior and interior surfaces of the egg membranes indicating penetration of these barriers. PMID- 11770639 TI - Broiler carcass contamination with Campylobacter from feces during defeathering. AB - Three sets of experiments were conducted to explore the increase in recovery of Campylobacter from broiler carcasses after defeathering. In the first set of experiments, live broilers obtained from a commercial processor were transported to a pilot plant, and breast skin was sampled by a sponge wipe method before and after defeathering. One of 120 broiler breast skin samples was positive for Campylobacter before defeathering, and 95 of 120 were positive after defeathering. In the second set of experiments, Campylobacter-free flocks were identified, subjected to feed withdrawal, and transported to the pilot plant. Carcasses were intracloacally inoculated with Campylobacter (10(7) CFU) just prior to entering the scald tank. Breast skin sponge samples were negative for Campylobacter before carcasses entered the picker (0 of 120 samples). After defeathering, 69 of 120 samples were positive for Campylobacter, with an average of log10 2.7 CFU per sample (approximately 30 cm2). The third set of experiments was conducted using Campylobacter-positive broilers obtained at a commercial processing plant and transported live to the pilot plant. Just prior to scalding, the cloacae were plugged with tampons and sutured shut on half of the carcasses. Plugged carcasses were scalded, and breast skin samples taken before and after defeathering were compared with those collected from control broilers from the same flock. Prior to defeathering, 1 of 120 breast skin sponge samples were positive for the control carcasses, and 0 of 120 were positive for the plugged carcasses. After passing through the picker, 120 of 120 control carcasses had positive breast skin sponge samples, with an average of log10 4.2 CFU per sample (approximately 30 cm2). Only 13 of 120 plugged carcasses had detectable numbers of Campylobacter on the breast skin sponge, with an average of log10 2.5 CFU per sample. These data indicate that an increase in the recovery of Campylobacter after defeathering can be related to the escape of contaminated feces from the cloaca during defeathering. PMID- 11770640 TI - Evaluation of subtherapeutic use of the antibiotics apramycin and carbadox on the prevalence of antimicrobial-resistant Salmonella infection in swine. AB - The antibiotics apramycin and carbadox were fed to growing swine, and the prevalence of Salmonella isolates that are resistant to apramycin and related aminoglycoside antibiotics was examined. Three hundred twelve Salmonella-positive pigs raised on one of five farms in an integrated swine operation and slaughtered at a central plant were used. All farms fed carbadox during the grower phase, and two farms administered apramycin during the first 21 days of age. Ileocolic lymph nodes and cecal contents were sampled at slaughter. One hundred of the 312 pigs were randomly selected to examine apramycin- and carbadox-resistant Salmonella infection, while all 312 pigs were used to evaluate the association between apramycin exposure and infection with Salmonella organisms resistant to amikacin, gentamicin, kanamycin, and streptomycin. Antimicrobial resistance was determined using disk diffusion and breakpoint concentrations. Apramycin treatment appeared to have little effect on apramycin- (12.5 versus 20.9%) or streptomycin- (76.4 versus 73.5%) resistant Salmonella isolates when averaged across farms and compared to control animals. Feeding carbadox resulted in carbadox-resistant Salmonella infection in only 5.3% of the isolates on one farm. The prevalence of amikacin-, gentamicin-, and kanamycin-resistant Salmonella isolates on farms feeding apramycin and carbadox were 0, 0, and 1.8%, respectively. Serogroup B was the most prevalent serogroup isolated, followed by C1 and E1. Apramycin and carbadox treatment did not appear to have any effect on the serogroup isolated. Subtherapeutic use of carbadox and apramycin did not appear to increase the prevalence of antimicrobial-resistant Salmonella in market-age swine. PMID- 11770641 TI - Efficacy of cetylpyridinium chloride in immersion treatment for reducing populations of pathogenic bacteria on fresh-cut vegetables. AB - The efficacy of cetylpyridinium chloride (CPC) immersion to reduce the numbers of three pathogenic bacteria (Listeria monocytogenes, Salmonella Typhimurium, and Escherichia coli O157:H7) on three different fresh-cut vegetables (broccoli, cauliflower, and radishes) was studied. The fresh-cut vegetables were inoculated with one of the three pathogenic bacteria at a concentration of 10(5) CFU/ml for 1 h at room temperature and then treated with 0.1 or 0.5% CPC immersion for 1 min. Both Salmonella Typhimurium and E. coli O157:H7 plates were incubated from 48 to 72 h at 37 degrees C, and L. monocytogenes plates were incubated from 72 to 96 h before being counted. The results of three experiments showed that for the average of the three vegetables treated with 0.1 and 0.5% CPC, L. monocytogenes was reduced by 2.85 and 3.70 log CFU/g, Salmonella Typhimurium by 2.37 and 3.15 log CFU/g, and E. coli O157:H7 by 1.01 and 1.56 log CFU/g, respectively, in comparison with the vegetables treated with water only. The 0.5% CPC treatment was significantly different (P < 0.05) from the 0.1% CPC treatment on reduction of L. monocytogenes, Salmonella Typhimurium, and E. coli O157:H7. The CPC residual on the treated vegetables and their washing solutions were evaluated by using high-performance liquid chromatography. PMID- 11770642 TI - Prevalence and contamination levels of Listeria monocytogenes in smoked fish and pate sold in Spain. AB - From March to November 2000, 170 samples of smoked fish and 182 samples of pate for sale in retail outlets and supermarkets in the nine provinces of Castilla and Leon (Spain) were analyzed for the prevalence of Listeria monocytogenes and other Listeria spp. L. monocytogenes was isolated from 38 (22.3%) of the 170 samples of smoked fish analyzed. Twenty of these positive samples contained L. monocytogenes at >100 CFU/g. Other Listeria spp., such as Listeria innocua (26 isolates), Listeria grayi (9), Listeria welshimeri (3), Listeria seeligeri (3), and Listeria ivanovii (2), were also detected. L. monocytogenes was isolated from 5.4% of the 182 samples of pate. Only 1 of the 10 positive samples harbored >100 L. monocytogenes CFU/g. Two other species of Listeria were observed in pate: L. innocua (12 isolates) and L. grayi (2). PMID- 11770643 TI - A new kinetic model for thermal inactivation of microorganisms: development and validation using Escherichia coli O157:H7 as a test organism. AB - A new kinetic model has been proposed to simulate the nonlinear behavior of survivor curves frequently observed in thermal inactivation of microorganisms. This model incorporates a time component into the first-order inactivation kinetics and is capable of describing the linear, convex, and concave survivor curves. The model was validated using Escherichia coli O157:H7 as a test microorganism. Ground beef (93% lean) samples inoculated to 10(7) to 10(8) CFU/g of meat were subjected to immersion heating at 55, 57.5, 60, 62.5, and 65 degrees C, respectively, in a water bath. All the survivor curves in this study showed upward concavity. Linear and nonlinear regressions were used to fit the survivor curves to the linear first-order inactivation kinetics and the proposed model. Analyses showed that the new kinetic model provides a much better estimate of the thermal inactivation behavior of E. coli O157:H7 in ground beef. PMID- 11770644 TI - Thermal lethality of Salmonella Senftenberg and Listeria innocua in fully cooked and packaged chicken breast strips via steam pasteurization. AB - Fully cooked chicken breast strips were surface inoculated to contain 9 log10 (CFU/g) Salmonella Senftenberg or Listeria innocua. The inoculated products were vacuum packaged in 0.2-mm-thick barrier bags (241 by 114 mm), then steam pasteurized at 88 degrees C in a continuous process for 26 to 40 min or in a batch process for 33 to 41 min. After the treatments, the products were analyzed for the survivors of Salmonella or Listeria. The models were developed to correlate the surviving rate of Salmonella and Listeria with cooking time for both continuous and batch processes. A cooking time of 34 min was needed to achieve 7 logs of the reduction in a batch process. To achieve the same log reduction, a longer (6 min) cooking time was needed in a batch process than in a continuous process. The results from this study will be useful for processors to evaluate postcooking treatment procedures for ready-to-eat meat products. PMID- 11770645 TI - Confocal microscopy and microbial viability detection for food research. AB - Confocal microscopy offers several advantages over other conventional microscopic techniques as a tool for studying the interaction of bacteria with food and the role of food microstructure in product quality and safety. When using confocal microscopy, samples can be observed without extensive preparation processes, which allows for the evaluation of food without introducing artifacts. In addition, observations can be made in three dimensions without physically sectioning the specimen. The confocal microscope can be used to follow changes over a period of time, such as the development of the food structure or changes in microbial population during a process. Microbial attachment to and detachment from food and food contact surfaces with complex three-dimensional (3-D) structures can be observed in situ. The fate of microbial populations in food system depends on processing, distribution, and storage conditions as well as decontamination procedures that are applied to inactivate and remove them. The ability to determine the physiological status of microorganisms without disrupting their physical relationship with a food system can be useful for determining the means by which microorganisms survive decontamination treatments. Conventional culturing techniques can detect viable cells; however, these techniques lack the ability to locate viable cells in respect to the microscopic structures of food. Various microscopic methods take advantage of physiological changes in bacterial cells that are associated with the viability to assess the physiologic status of individual cells while retaining the ability to locate the cell within a food tissue system. This paper reviews the application of confocal microscopy in food research and direct observation of viable bacteria with emphasis on their use in food microbiology. PMID- 11770646 TI - Crohn's disease and Mycobacterium avium subsp. paratuberculosis: current issues. AB - Crohn's disease is a chronic debilitating inflammatory bowel disease of unknown etiology. Proposed causes include bacterial or viral infection, diet or exposure to tobacco smoke, genetic abnormality, and immune dysfunction. The bacterium Mycobacterium avium subsp. paratuberculosis (Map) has received much research attention as a potential cause of the disease. Map causes Johne's disease in ruminants. The pathology of Johne's disease superficially resembles that of Crohn's disease in humans. Some researchers have shown evidence of Map in intestinal tissues of Crohn's disease patients. Studies are in progress to investigate the possibility that Map exists in milk from infected cows and survives pasteurization. This is a controversial subject with the potential for media attention and public outcry. We examined the current literature and concluded that insufficient evidence exists at this time to implicate any one factor, including Map in milk, as the definitive cause of Crohn's disease. The high degree of uncertainty in this issue requires regulators to recognize the need for effective risk communication as ongoing research provides additional information about the disease. PMID- 11770647 TI - Groundless attack on an uncommon man: William Haddon, Jr, MD. PMID- 11770648 TI - International comparisons: we need to know a lot more. PMID- 11770649 TI - International comparisons: they do help and are essential for avoiding type III error. PMID- 11770650 TI - The tooth fairy, Santa Claus, and the hard core drinking driver. PMID- 11770651 TI - Cost effectiveness analysis of a smoke alarm giveaway program in Oklahoma City, Oklahoma. AB - OBJECTIVE: To estimate the cost effectiveness of the Lifesavers Residential Fire and Injury Prevention Program (LRFIPP), a smoke alarm giveaway program. SETTING: In 1990, the LRFIPP distributed over 10,000 smoke alarms in an area of Oklahoma City at high risk for residential fire injuries. The program also included fire prevention education and battery replacement components. METHODS: A cost effectiveness analysis was conducted from the societal and health care systems perspectives. The study compared program costs with the total costs of medical treatment and productivity losses averted over a five year period. Fatal and non fatal residential fire related injuries prevented were estimated from surveillance data. Medical costs were obtained from chart reviews of patients with fire related injuries that occurred during the pre-intervention period. RESULTS: During the five years post-intervention, it is estimated that the LRFIPP prevented 20 fatal and 24 non-fatal injuries. From the societal perspective, the total discounted cost of the program was $531,000. Total discounted net savings exceeded $15 million. From the health care system perspective, the total discounted net savings were almost $1 million and would have a net saving even if program effectiveness was reduced by 64%. CONCLUSIONS: The program was effective in reducing fatal and non-fatal residential fire related injuries and was cost saving. Similar programs in other high risk areas would be good investments even if program effectiveness was lower than that achieved by the LRFIPP. PMID- 11770652 TI - National attitudes concerning gun carrying in the United States. AB - OBJECTIVES: To determine public attitudes in the United States concerning gun carrying. SETTING: In the past 15 years, many state legislatures have passed laws making it easier for United States citizens to carry concealed firearms, not only on the street but into various locations, including churches and government buildings. METHODS: National random digit dial telephone surveys conducted in 1996 and 1999 asked questions concerning the public's feelings of safety as more people in their community carry firearms, and whether, in the language of the question, respondents believe "regular" citizens should be allowed to carry guns into public or government buildings. RESULTS: Americans feel less safe rather than more safe as more people in their community begin to carry guns. By margins of at least nine to one, Americans do not believe that "regular" citizens should be allowed to bring their guns into restaurants, college campuses, sports stadiums, bars, hospitals, or government buildings. CONCLUSIONS: The public believes that increased gun carrying by others reduces rather than increases their safety. Overwhelmingly, the public believes that in many venues gun carrying should be prohibited. PMID- 11770653 TI - Kentucky's graduated driver licensing program for young drivers: barriers to effective local implementation. AB - OBJECTIVES: To examine the implementation of graduated driver licensing (GDL) in Kentucky and to use the data collected to recommend actions to enhance the effectiveness of the GDL program. METHODS: Data were acquired from surveys of 700 law enforcement officers and more than 40 judges and from interviews with 100 persons who implement or are affected by Kentucky's GDL program-for example, traffic court judges, licensing clerks, law enforcement officers, insurance agents, driving instructors, parents, and employers of teens. Transcripts from interviews were analyzed using a qualitative data analysis computer program. RESULTS AND CONCLUSIONS: Participants noted a widespread lack of awareness of the night-time driving restriction and a substantial number of young drivers receiving little driving time during the learner permit phase. It appeared that specific GDL provisions can be difficult for judges and law officers to enforce and the penalty of license suspension after several traffic violations may not be a sufficient deterrent. Efforts are needed to increase parental awareness of GDL provisions, GDL purpose, and their teen's traffic violations and to increase parental enforcement of restrictions that are difficult for law enforcement agencies to monitor, such as the night-time driving restriction and the adult supervision requirement. PMID- 11770654 TI - Impact of graduated driver licensing restrictions on crashes involving young drivers in New Zealand. AB - OBJECTIVE: To determine the impact on young driver crashes of the three main driving restrictions in the New Zealand graduated driver licensing (GDL) system: night-time curfew, no carrying of young passengers, and a blood alcohol limit of 30 mg/100 ml. METHOD: The database for this study was created by linking police crash reports to hospital inpatient records (1980-95). Multivariate logistic regression was used to compare car crashes involving a young driver licensed before GDL (n=2,252) with those who held a restricted graduated licence (n=980) and with those who held a full graduated licence (n=1,273), for each of the main driving restrictions. RESULTS: Compared with the pre-GDL group, the restricted licence drivers had fewer crashes at night (p=0.003), fewer involving passengers of all ages (p=0.018), and fewer where alcohol was suspected (p=0.034), but not fewer involving young casualties (p=0.980). Compared with the pre-GDL drivers, those with the full graduated licence had fewer night crashes (p=0.042) but did not differ significantly for any of the other factors examined. CONCLUSION: These results suggest that some of the GDL restrictions, especially the night-time curfew, have contributed to a reduction in serious crashes involving young drivers. PMID- 11770655 TI - Exposure to violence and its relationship to psychopathology in adolescents. AB - OBJECTIVES: This study aimed to establish prevalence of adolescents' exposure to violence and related symptoms in the South African context and to explore relationships between exposure and symptoms. SETTING: Four high schools in Cape Town, South Africa. METHODS: Self report questionnaires were administered to 104 students. Types of violence explored included: witnessing or being a victim of violence perpetrated by someone known to the child or in the home and witnessing or being a victim of violence perpetrated by a stranger. The Harvard Trauma Scale, Beck Depression Inventory, and Zung Self-Rating Anxiety Scale were used to assess potentially related symptoms. RESULTS: The majority of children had been exposed to at least one type of violence, and exposure to the one type of violence was related to the other type. Symptoms of post-traumatic stress disorder and depression appear to be related to most types of exposure to violence, but anxiety symptoms only to exposure to violence perpetrated by someone known to the child or in the home. CONCLUSIONS: Rates of exposure to violence, and related symptoms, were unacceptably high. Symptoms were associated with exposure to violence. PMID- 11770656 TI - Barriers to safe hot tap water: results from a national study of New Zealand plumbers. AB - INTRODUCTION: Many countries still have unacceptably high hospitalizations and deaths from scalds from hot tap water. Prevention strategies implemented in some countries may not work in others. Legislation aimed at changing environments that are conducive to hot tap water scalds may not be effective in many situations for a number of reasons, including lack of acceptability and practicality. METHOD: A qualitative study of a purposefully selected group of craftsman plumbers across New Zealand was conducted using a structured format with open ended questions. The questionnaire was administered by telephone. Information was sought on the opinions, knowledge, and practice of these plumbers regarding hot tap water safety in homes. RESULTS: Several barriers to hot tap water safety in homes were identified by the plumbers. These included common characteristics of homes with unsafe hot tap water, such as hot water systems heated by solid fuel, and public ignorance of hot tap water safety. Other factors that emerged from the analysis included a lack of knowledge by plumbers of the hazards of hot tap water, as well as a lack of importance given to hot tap water safety in their plumbing practice. Shower performance and the threat to health posed by legionella were prioritized over the prevention of hot tap water scalds. CONCLUSION: The findings of this study allow an understanding of the practical barriers to safe hot tap water and the context in which interventions have been applied, often unsuccessfully. This study suggests that plumbers can represent a barrier if they lack knowledge, skills, or commitment to hot tap water safety. Conversely, they represent a potential source of advocacy and practical expertise if well informed, skilled, and committed to hot tap water safety. PMID- 11770657 TI - Non-fatal animal related injuries to youth occurring on farms in the United States, 1998. AB - OBJECTIVE: To provide data on the magnitude and patterns of animal related on farm injuries to youth in the United States. DATA SOURCE: A survey of 26,000 farm households conducted for the National Institute for Occupational Safety and Health by the United States Department of Agriculture in 1998. SUBJECTS: Youth younger than 20 years of age. RESULTS: There were an estimated 6,438 animal related on-farm injuries to youth in 1998. 70% occurred to farm residents; 69% were work related. Males accounted for 64% and approximately 41% occurred to those younger than 10; 37% involved horses and 31% cattle. Most horse related injuries occurred to females and a majority of the cattle related injuries were to males. Additionally, most of the cattle related injuries were work related, while horse related injuries were mainly nonwork. CONCLUSIONS: One out of every five youth injuries occurring on farms in the United States is animal related. These animal related injuries were due to both work and non-work related exposures. The large number of horse and cattle related injuries highlights a need for intervention strategies based on the injury circumstances common to these animals. PMID- 11770658 TI - Predictors of injury from fighting among adolescent males. AB - OBJECTIVES: To identify violence related behaviors associated with injuries among adolescent males involved in fights. METHODS: Data from the National Longitudinal Study of Adolescent Health were used to develop weighted estimates of injury prevalence and associations between injury and violence related behaviors. RESULTS: Forty seven per cent injured others and 18% were themselves injured in a fight among adolescent males in the preceding 12 months. Group fighting, fighting with strangers, and weapon use were predictive of injury in this sample. CONCLUSIONS: These findings suggest that injuries associated with fighting are a health risk among adolescent males. Certain behaviors, such as fighting in groups and fighting with strangers, increase the likelihood of injuries requiring medical attention. PMID- 11770660 TI - Dog bite and injury prevention--analysis, critical review, and research agenda. AB - OBJECTIVES: To analyze Australian dog bite injury data and make international comparisons; to review risk and protective factors relating to the dog, injured person, and environment; and to recommend action for prevention and research. METHODS: Australian dog bite injury data, complemented by detailed Victorian and regional data from routine health records and vital statistics, were analyzed to determine incidence, severity, nature, circumstances, and trends. International comparison data were extracted from published reports. Risk and protective factor studies were selected for review from electronic and bibliographic searches where data were recent, sample sizes substantial, and bias limited. RESULTS: The Australian dog bite death rate (0.004/100,000) is lower than both the United States (0.05-0.07/100,000) and Canadian rates (0.007/100,000). Victorian hospitalized trend rates were stable between 1987 and 1998, but there was a decline for children <5 years (p=0.019) corresponding with a reduction in dog ownership. Children 0-4 years have the highest rate of serious injury, particularly facial. Adults have longer hospitalizations, most frequently for upper extremity injury. Risk factors include: child, males, households with dogs, certain breeds, male dogs, home location, and leashed dog. CONCLUSIONS: Dog bite rates are high and it may therefore be assumed that current preventative interventions are inadequate. Responsible dog ownership, including separating young children from dogs, avoiding high risk dogs, neutering, regulatory enforcement, and standardized monitoring of bite rates are required. Controlled investigations of further risk and protective factors, and validated methods of breed identification, are needed. PMID- 11770659 TI - Hospitalized fall injuries and race in California. AB - OBJECTIVE: To compare risks for falls and their consequences among four major race/ethnic groups in California. METHODS: Cases are 104,902 hospital discharges of California residents with a same level fall injury as the principal external cause of injury. Included are all discharges for a first hospitalization for a given injury in any California non-federal hospital from 1995-97. Analysis includes crude and age standardized rates to describe risks, diagnoses, and consequences. RESULTS: Rates per 100 000 for same level hospitalized fall injuries for whites (161) are distinctively higher than for blacks (64), Hispanics (43), and Asian/Pacific Islanders (35). Whites are more likely to have a fracture diagnosis and to be discharged to long term care rather than home, suggesting a poorer outcome or greater severity. Same level falls absorb a large proportion of hospital resources directed to the treatment of injuries. CONCLUSIONS: In a four way comparison among race/ethnic groups, whites are distinguished by their high incidence, rates of fracture, and unfavorable discharge status. Prevention, particularly aimed at whites, has potential to improve health and save treatment resources. PMID- 11770661 TI - Vehicles reversing or rolling backwards: an underestimated hazard. AB - OBJECTIVES: A retrospective analysis of injuries caused by vehicles that were reversing or rolling backwards to establish guidelines for prevention was performed. PATIENTS AND METHODS: Medical records and questionnaires completed by parents for 32 children admitted to the Department of Pediatric Surgery, Graz, within the past eight years, were analysed. RESULTS: The median age was 2.1 years (1.0-14.0 years). Fourteen of 32 of the cars were driven by family members (43.8%); three were rolling backwards without a driver (9.4%). The median injury severity score was 3 (1-27) and the most common injuries were contusions (40.6%), fractures (31.3%), and lacerations/burns (21.9%). Most incidents occurred in driveways (37.5%) or farmyards (21.9%). Altogether 70.3% of children sustained "run-over" injuries, 29.6% were hit by the rear bumper or injured by a breaking window. CONCLUSIONS: Toddlers playing in driveways or farmyards are at risk of a injury caused by reversing vehicles/vehicles rolling backwards. PMID- 11770662 TI - Knowledge, attitude, and practice of sugarcane crushers towards hand injury prevention strategies in India. AB - INTRODUCTION: Injuries of the hand have an enormous impact on hand function and on quality of life. Occupational injuries are a major cause of morbidity and mortality in India and their incidence has been steadily increasing. Sugarcane crushers produce juice using dangerous procedures. OBJECTIVE: The objective of this study was to determine the knowledge, attitudes, and practices among sugarcane crushers in India and thus assist in the formulation of effective preventive strategies. SETTING: A block (area) in the Vellore District, South India (population 100 000). SUBJECTS AND METHODS: All sugarcane crushers living in this area (n = 32) were included. A single observer, using a questionnaire, conducted personal on-site interviews. RESULTS: Carelessness was involved in 63% of injuries. Sixteen per cent felt that machines with improved safety features are required; 40% supported the use of special gloves, although 19% considered them a hindrance. Eighty eight per cent did not consider the long duration of work as a risk factor and 38% were fatalistic (God's will); 50% thought the injuries were due to "bad luck". CONCLUSION: Sugarcane crushers do not perceive the need for safer equipment. To overcome fatalistic views, and persuade this group to take other safety measures, safety education will need to take into consideration their socioeconomic and educational status. PMID- 11770663 TI - A new department for injuries and violence prevention at the World Health Organization. PMID- 11770664 TI - Accuracy of external cause of injury codes reported in Washington State hospital discharge records. AB - OBJECTIVE: To evaluate the accuracy of external cause of injury codes (E codes) reported in computerized hospital discharge records. METHODS: All civilian hospitals in Washington State submit computerized data for each hospital discharge to a file maintained by the Department of Health. In 1996, 32 hospitals accounted for 80% of the injury related discharges in this file; from these hospitals, we sampled 1,260 computerized records for injured patients in a stratified, but random, manner. An expert coder then visited the 32 study hospitals, reviewed the medical records that corresponded to each computerized record, and assigned an E code for that hospitalization. The computerized E code information was compared with codes provided by the expert reviewer. RESULTS: The incidence of hospitalization for injury based upon computerized hospital discharge data was very similar to that based upon chart review: incidence rate ratio 1.0 (95% confidence interval 1.00 to 1.02). Computerized hospital discharge data correctly ranked injuries in regard to both mechanism and intent. Overall agreement on coding was 87% for mechanism of injury, 95% for intent of injury, and 66% for the complete E code. The sensitivity of computerized hospital discharge data for identification of falls, motor vehicle traffic injuries, poisonings, and firearm injuries was 91% or better. The predictive value positive of coding for these four categories of injury ranged from 88% for motor vehicle traffic injuries to 94% for poisonings. The amount of agreement for intent coding ranged from 84% for firearm injuries to 99% for falls. Agreement on coding of the complete E code ranged from 57% for firearm injuries to 72% for poisonings. CONCLUSIONS: Computerized hospital discharge data can be used with confidence to determine how many injuries are treated in a hospital setting and the relative magnitude of various categories of injury. E codes reported in hospital discharge data are a reliable source of information on the types of information most often used for injury related analyses and priority setting. The detail codes (complete E codes) reported in hospital discharge codes are less reliable and must be used with caution. PMID- 11770665 TI - Use of Washington State newspapers for submersion injury surveillance. AB - OBJECTIVES: To evaluate the usefulness of newspapers as a surveillance tool for submersion injury, the proportion of submersion events and important details reported in Washington State newspapers was determined. It was also determined whether a letter sent to newspaper editors to encourage reporting changed the proportion and content of reported submersion events. METHODS: Newspaper articles regarding submersion were collected from 225 Washington newspapers from June 1993 through September 1998. Newspaper articles were linked to computerized state death and hospital records. Reporting during periods before and after a letter was sent encouraging more newspaper articles on submersion injury and preventative factors was compared. RESULTS: A total of 1,874 submersion victims were identified in the three data sources. Of the 983 victims who had a death certificate, 52% were reported in at least one news article. Of the 471 persons in hospital discharge data, 25% were reported in a newspaper. Reporting of pediatric victims who died increased from 63% to 79% (p=0.008); reporting of hospitalized persons increased from 23% to 27% (p=0.3). There were increases in reporting of swimming ability (7% to 15%, p<0.001), supervision (82% to 91%, p<0.001), and alcohol use (7% to 24%, p<0.001). Reporting of life vest use decreased (35% to 23%, p<0.001). CONCLUSIONS: Newspapers failed to report about one half of fatal submersions and three quarters of submersions that resulted in a hospitalization. An effort to improve reporting was associated with an increase in the proportion of pediatric drownings that were reported, but a consistent improvement in content was found. The usefulness of newspaper articles as a surveillance tool may be limited. PMID- 11770666 TI - The risk compensation theory and bicycle helmets. PMID- 11770667 TI - Safety in numbers? A new dimension to the bicycle helmet controversy. PMID- 11770668 TI - Changes in speech intelligibility of postlingually deaf adults after cochlear implantation. AB - OBJECTIVE: This study examines changes in the intelligibility of CVC words spoken by postlingually deafened adults after they have had 6 to 12 mo of experience with a cochlear implant. The hypothesis guiding the research is that the intelligibility of these speakers will improve after extended use of a cochlear implant. The paper also describes changes in CVC word intelligibility analyzed by phoneme class and by features. DESIGN: The speech of eight postlingually deaf adults was recorded before activation of the speech processors of their cochlear implants and at 6 mo and 1 yr after activation. Seventeen listeners with no known impairment of hearing completed a word identification task while listening to each implant user's speech in noise. The percent information transmitted by the speakers in their pre- and postactivation recordings was measured for 11 English consonants and eight vowels separately. RESULTS: An overall improvement in word intelligibility was observed: seven of the eight speakers showed improvement in vowel intelligibility and six speakers showed improvement in consonant intelligibility. However, the intelligibility of specific consonant and vowel features varied greatly across speakers. CONCLUSIONS: Extended use of a cochlear implant by postlingually deafened adults tends to enhance their intelligibility. PMID- 11770669 TI - Language-specific, hearing-related changes in vowel spaces: a preliminary study of English- and Spanish-speaking cochlear implant users. AB - OBJECTIVE: This study investigates the role of hearing in vowel productions of postlingually deafened cochlear implant users. Two hypotheses are tested that derive from the view that vowel production is influenced by competing demands of intelligibility for the listener and least effort in the speaker: 1) Hearing enables a cochlear implant user to produce vowels distinctly from one another; without hearing, the speaker may give more weight to economy of effort, leading to reduced vowel separation. 2) Speakers may need to produce vowels more distinctly from one another in a language with a relatively "crowded" vowel space, such as American English, than in a language with relatively few vowels, such as Spanish. Thus, when switching between hearing and non-hearing states, English speakers may show a tradeoff between vowel distinctiveness and least effort, whereas Spanish speakers may not. DESIGN: To test the prediction that there will be a reduction of average vowel spacing (AVS) (average intervowel distance in the F1-F2 plane) with interrupted hearing for English-speaking cochlear implant users, but no systematic change in AVS for Spanish cochlear implant users, vowel productions of seven English-speaking and seven Spanish speaking cochlear implant users, who had been using their implants for at least 1 yr, were recorded when their implant speech processors were turned off and on several times in two sessions. RESULTS: AVS was consistently larger for the English speakers with hearing than without hearing. The magnitude and direction of AVS change was more variable for the Spanish speakers, both within and between subjects. CONCLUSION: Vowel distinctiveness was enhanced with the provision of some hearing in the language group with a more crowded vowel space but not in the language group with fewer vowels. The view that speakers seek to minimize effort while maintaining the distinctiveness of acoustic goals receives some support. PMID- 11770670 TI - A longitudinal study of electrode impedance, the electrically evoked compound action potential, and behavioral measures in nucleus 24 cochlear implant users. AB - OBJECTIVE: The primary goal of this study was to examine changes that may occur in electrode impedance, electrically evoked compound action potential (EAP) threshold and slope of the EAP growth function, and behavioral measures of threshold T-level) and maximum comfort (C-level) over time in both adult and child cochlear implant users. Secondary goals were to determine whether changes in these measures are consistent between children and adults, and to determine whether behavioral measures (MAP T- and C-levels) and electrophysiologic measures (EAP thresholds) exhibit the same trends over time. DESIGN: Thirty-five children and 33 adults implanted with the Nucleus CI24M between November 1996 and August 1999 participated in this study. Subjects were included in this study if 1) they had used their implant for at least 1 yr after device connection, and 2) they had participated in the necessary data collection at a minimum number of the time intervals assessed in this study. EAP threshold, slope of the EAP growth function, and common ground electrode impedance measures were collected intraoperatively, at initial stimulation, and at several subsequent visits up to 2 yr post initial stimulation. MAP T- an d C-levels weremeasured at initial stimulation and at the same time intervals as described above. RESULTS: Changes in electrode impedance, EAP thresholds, and slope of the EAP growth function from measures made intraoperatively, at initial stimulation, and at 1 to 2 mo post initial stimulation were similar in both children and adults. Beyond the 1- to 2 mo visit, children exhibited significant increases in electrode impedance, EAP thresholds, slope, and MAP T-levels, whereas these samemeasures in adults remained relatively stable. EAP thresholds in children stabilized by the 3- to 8 mo visit, and electrode impedance stabilized by the 6- to 8-mo visit, while slope of the EAP growth function, MAP T-levels,and MAP C-levels werestable by 1 yr post initial stimulation. C-levels in adults increased up to 1 yr post initial stimulation; however, the amount of increase was much smaller than that seen in children. In both children and adults, longitudinal trends in EAP thresholds mirrored T-level more closely than C-level. CONCLUSIONS: The results of this study suggest that peripheral changes occur in many children that do not generally occur in adults within the first year of cochlear implant use. One implication of these results is that if EAP thresholds are to be used to assist in programming the speech processor for children, it is best to make those measures at the same time interval as device programming rather than using measures made intraoperatively or at the initial programming session to set MAP levels at later visits. PMID- 11770671 TI - The selection and validation of output sound pressure level in multichannel hearing aids. AB - OBJECTIVE: To validate the Australian National Acoustic Laboratories' (NAL) procedure for prescribing output sound pressure level (OSPL) for multichannel hearing aids (Dillon & Storey, 1998) DESIGN: The NAL OSPL prescriptive procedure for multichannel hearing aids was used to calculate Predicted OSPL, Predicted Maximum Acceptable OSPL and Predicted Minimum Acceptable OSPL for 20 subjects with sensorineural hearing loss fitted with a 2-channel linear hearing aid. Subjects rated the speech clarity and quality of average (65 dBA) and loud (80 dBA) speech, in quiet and in noise, with the hearing aid set to a number of OSPL settings. These data were used to evaluate the validity of the Predicted OSPL. Frequency-specific loudness discomfort levels (LDLs) were measured to determine whether use of measured LDLs would improve the accuracy of the prediction. RESULTS: The Predicted Minimum Acceptable OSPL was in good agreement with the measured minimum acceptable OSPL for both the low- and high-frequency channels. The Predicted Maximum Acceptable OSPL was in good agreement with the measured maximum acceptable OSPL for the low-frequency channel, but was only a fair predictor for the high-frequency channel. The use of measured LDLs rather than predicted LDLs did little to improve the accuracy of the fitting. A direct comparison between the NAL single-channel and multichannel prescribed OSPL settings showed that most listeners rated speech clarity higher for the multichannel settings. CONCLUSIONS: In two channel hearing aids, the NAL Predicted Minimum Acceptable OSPL and Predicted Maximum Acceptable OSPL are reasonable predictors of minimum and maximum OSPL levels measured using sound clarity and quality ratings. The results of this study support the use of the NAL prescriptive formula for setting OSPL in multichannel hearing aids. Such settings should be verified by having the listener rate the loudness of an intense speech signal. If tolerance problems are evident, the OSPL in the high-frequency channel(s) should be reduced first. PMID- 11770672 TI - Comparing loudness normalization (IHAFF) with speech intelligibility maximization (NAL-NL1) when implemented in a two-channel device. AB - OBJECTIVE: At least two rationales are available for fitting wide dynamic range compression hearing aids. The goal of one rationale is to normalize loudness, and the goal of the second rationale is to maximize speech intelligibility. Neither rationale has been validated against other fitting rationales for the range of input levels common to the hearing aid user in the real world. The goal of the study was to compare the two rationales when implemented in a 2-channel compression hearing aid. DESIGN: Loudness normalization and speech intelligibility maximization were implemented using the Independent Hearing Aid Fitting Forum (IHAFF) and the National Acoustic Laboratories' Nonlinear (NAL-NL1) prescriptive formulas. Twenty-four subjects (eight for each of three groups of mild flat, moderate/severe flat, and steeply sloping hearing loss) participated in the study. Each subject completed an initial laboratory test, field test, and final laboratory test. The laboratory test consisted of a paired-comparison judgment for each prescriptive formula using four stimuli under both quiet and noisy listening conditions and a sentence recognition test using Bamford-Kowal Bench sentences. In the field test, subjects evaluated the two rationales in individually selected everyday listening conditions for 4 wk. A digital simulation of the fitting rationales implemented in two channels was used for laboratory testing and a digital 2-memory, 2-channel device was used for field testing. Subjects adjusted the overall gain of each response to their preferred listening level in both the laboratory and in the field. RESULTS: Data collected in the laboratory before and after the field test showed no indication of significant learning or acclimatization effects. For each stimulus presented in the paired-comparison test more subjects preferred NAL-NL1 than preferred IHAFF. For the sentence recognition test, subjects performed significantly better with NAL-NL1 than IHAFF in a low-frequency weighted background noise. Sixteen out of 22 subjects who completed the field test reported a preference for the NAL-NL1 response. The remaining six subjects preferred IHAFF. The paired-comparison test and field test revealed that while the achieved root-mean-square (rms) difference between fittings for an input level of 65 dB SPL was small, the preference for either rationale was small. As the rms difference between fittings increased, the score in favor of NAL-NL1 increased. The correlation between the differences in satisfaction score obtained in the field test and the rms differences between the responses fitted was statistically significant. CONCLUSIONS: When the two fitting rationales prescribed substantially different responses for a 65 dB SPL input and these differences were achieved in the fitting, then the subjects preferred NAL NL1. Even when the difference between fittings was small, the subjects preferred and performed better with NAL-NL1 when listening in a low-frequency weighted background noise. PMID- 11770673 TI - The preferred number of channels (one, two, or four) in NAL-NL1 prescribed wide dynamic range compression (WDRC) devices. AB - OBJECTIVE: The recently introduced NAL-NL1 rationale for fitting WDRC devices prescribes a relatively high compression threshold and prescribes compression ratios lower than those prescribed by loudness normalization rationales. The aim of this study was to investigate whether the compression characteristic prescribed by NAL-NL1 is most effective in a single-channel scheme or in a multi channel scheme. DESIGN: Twenty-four subjects with flat or steeply sloping hearing loss participated in the study. One, two, and four channels were implemented digitally in the laboratory and evaluated on the basis of a paired-comparison test and a speech recognition test. The test stimuli consisted of speech and noise presented at average input levels, and speech and noise alternating every 3 sec among different input levels. The single-channel and 2-channel NAL-NL1 prescriptions were also evaluated in individually selected everyday situations in the field using a digital 2-memory device. RESULTS: The three compression schemes produced no significant difference in speech recognition scores. Most subjects showed no preference for either scheme in the paired-comparison test. Those who did mainly selected the single-channel scheme. These preferences can be explained on the basis on audibility and quality. In the field all subjects with a steeply sloping loss, but one, preferred the 2-channel scheme. Among the subjects with a flat loss more preferred the single-channel scheme than preferred the 2-channel scheme. Statistical analyses showed that those who preferred the 2-channel scheme were fitted with significantly greater differences in the compression ratio in the high frequencies, and those who preferred the single-channel scheme were fitted with significantly greater differences in the high-frequency gain for a 65 dB input. CONCLUSIONS: Multi-channel compression prescribed according to NAL-NL1 in up to four channels showed no adverse effects on speech recognition relative to a single-channel scheme. The paired-comparison test showed a small, but explainable preference for the single-channel scheme. The field test revealed a preference for the 2-channel scheme by subjects with steeply sloping loss. When using the NAL-NL1 rationale it is recommended to use at PMID- 11770674 TI - Comparison of procedures to determine electrical stimulation thresholds in cochlear implant users. AB - OBJECTIVE: This study was designed to evaluate threshold estimation procedures for cochlear implantees, both for clinical and research purposes. Precision and testing time of eight procedures were evaluated. These procedures included three variations of two adaptive tasks and two variations of an adjustment procedure. DESIGN: Electrical thresholds were obtained with eight different procedures. For each procedure, one of three tasks was combined with one of four decision strategies. With the adjustment task, current level was adjusted from "inaudible" to "just audible" or from "clearly audible" to "just audible." With the two adaptive tasks (i.e., "count the number of pulses" and "choose the interval with the pulse"), current level was adjusted during the sequence of trials by subjects' preceding responses according to three decision criteria (Levitt, 1971). Experimental data were collected on both an apical and a basal channel of six Laura cochlear implantees, and test-retest measures were obtained for each procedure, channel and subject. Moreover, total testing time was recorded in each test, to examine the trade-off with precision, and to investigate the feasibility of the procedures in a clinical setting. RESULTS: In general, the "count the pulses" procedures yield higher threshold values than the "choose the interval with the pulse" and adjustment procedures. Precision was not a statistically significant factor, although the test-retest variation was approximately a factor of 2 larger in the adjustment procedures than in the adaptive procedures. Test duration differences were large. Moreover, analyses of the adaptive procedures showed that a stable estimate requires at least six reversals and that the first four reversals should not be taken into account for threshold estimation. CONCLUSIONS: In a clinical setting, where precision and time are important parameters, precise thresholds can be obtained with the adjustment procedure. However, for research purposes, it is advised to use the "choose the interval with the pulse" task together with one of the transformed up-down decision criteria. PMID- 11770675 TI - The effect of the audallion BEAMformer noise reduction preprocessor on sound localization for cochlear implant users. AB - OBJECTIVE: To assess the effect of the Audallion BEAMformer noise reduction preprocessor on the sound localization ability of children fitted unilaterally with the Nucleus 22-channel cochlear implant. DESIGN: Eight children aged 11 to 14 yr participated. Using three arrays of six loudspeakers, each child was tested in a semi-reverberant sound proof booth representative of a small office environment. The six loudspeakers were positioned 30 degrees apart in the horizontal plane at a distance of 1 m, spanning 150 degrees either directly in front of or to the left or right of the subject. The stimulus to be localized was a 300 msec broadband noise with a rise/decay of 50 msec. Subjects were tested with the BEAMformer in four possible settings, including one single microphone control condition, with each of the three loudspeaker arrays. One block of 60 forced-choice speaker identification trials was presented for each of the 12 listening conditions. On each trial, the stimulus was emitted by one of the six loudspeakers, randomly selected. RESULTS: Results demonstrated that subjects were unable to discriminate among sound sources arrayed horizontally in space using the cochlear implant microphone alone, or in combination, with the BEAMformer microphone located on the other ear. Results also showed that using the BEAMformer did not bias the perception of spatial location. CONCLUSIONS: The localization of acoustic stimuli in pediatric cochlear implant users was unaffected by the use of the Audallion BEAMformer. The apparent origin of most sounds appears to be pulled toward the implanted ear. Further studies are needed to validate findings. PMID- 11770676 TI - Air pollution in asthma: effect of pollutants on airway inflammation. AB - OBJECTIVES: The objective of this review is to examine the impact of air pollutants on airway inflammation, with an emphasis on the interaction of the effect of ozone, particulate matter, and endotoxin exposure and immunoglobulin E mediated airway inflammation. DATA SOURCES: This review examines the National Ambient Air Quality Standards and sources for different types of air pollution, as well as undertakes a review of epidemiologic and human challenge studies which address the impact of air contaminants in asthma and allergic inflammation. RESULTS: Epidemiologic and human challenge studies both demonstrate that ozone and endotoxin exposure can exacerbate allergic inflammation in the airway. Conversely, allergic processes may enhance individual response to air pollutants as well. CONCLUSIONS: Ozone and particulate matter are both important agents in inducing asthma exacerbation. However, these pollutants have not been implicated in development of immunoglobulin E responses to neoantigens. Decreased exposure to these pollutants or a better understanding of the processes by which they impact the airway may be useful in decreasing asthma severity. PMID- 11770677 TI - Is diesel the cause for the increase in allergic disease? AB - LEARNING OBJECTIVES: The purpose of this review is to objectively critique available data regarding the role of diesel exhaust particles (DEPs) in allergic disease. Readers of this review should understand the ways in which diesel particulates can affect human airways and the extent of the scientific data which are currently available. DATA SOURCES: Data were obtained from published studies and reviews. STUDY SELECTION: The specific reviewed studies selected for this review met the following criteria: human and animal in vivo, in vitro, and pulmonary dosimetry studies, as well as epidemiologic studies to examine the role of DEPs and particulates on the airways. RESULTS: The results of the published studies show that although DEPs may play a role in the increased levels of allergic disorders through a number of immunologic mechanisms, it remains to be proven whether it is responsible for the recent rise in the prevalence of asthma and other allergic disorders. CONCLUSIONS: Further studies in humans are needed to elucidate the mechanisms by which DEPs may be responsible for the increased prevalence of allergic disorders. PMID- 11770678 TI - Environmental pollution and allergy. AB - OBJECTIVES: Among the theories supporting the increase of allergic diseases in modern western countries during the last several decades is the concept that environmental pollutants may play a vital role. Reading this article will enable the reader to recognize the effect of different types of environmental pollution on the development, modulation, and persistence of allergic reactions. DATA SOURCES: Data sources include references to relevant articles and texts. To characterize the influence of environmental pollutants on allergic reactions (allergotoxicology), epidemiologic, clinical, and experimental data are considered. RESULTS: The investigations show that air pollution patterns differ with respect to their effect upon allergies. Classical air pollution (type I) with high sulfur dioxide and dust particles seems not to be associated with allergic disease in humans. However, type II pollution characterized by elevation of oxides of nitrogen (NOx), ozone (O3), tobacco smoke, fine and ultrafine particulate matter, and diesel exhaust particles seems to enhance allergic disease. CONCLUSIONS: The data suggest that environmental pollution can act at different levels and by complex interactions both outside and inside the individual and influence allergic diseases. PMID- 11770679 TI - Prevalence of atopy and asthma in eastern versus western Europe: why the difference? AB - LEARNING OBJECTIVES: This article reinforces the reader's knowledge of the epidemiology of allergy and asthma in eastern versus western European countries and the ability to recognize the different hypotheses formulated to explain the rising trend of allergic asthma in Europe. DATA SOURCES: Articles in English comparing the epidemiology of allergy in eastern versus western Europe published before December 31, 2000. RESULTS: Significant higher prevalences of atopy and allergic asthma were observed in the early 1990s among populations living in western compared with eastern European countries. Changes in lifestyle after the fall of the communist system were associated with an increasing trend of atopic sensitization and hay fever in former East Germany after only 6 to 8 years after the Germany reunification. It has been hypothesized that a similar "converging" trend in the prevalence of allergic asthma and of bronchial hyperresponsiveness may take longer periods. CONCLUSIONS: The prevalence of allergic asthma has increased decades earlier in western Europe with respect to eastern Europe. This is probably attributable to changes in lifestyle that had already occurred rather than to air pollution. The factors of a western lifestyle (diet, hygiene, varied allergen exposure) that have determined the difference in allergic asthma prevalence across Europe have yet to be identified. PMID- 11770680 TI - Cell and molecular biology of chemical allergy. AB - OBJECTIVE: The objective of this review is to provide current approaches to gain increased understanding of the molecular basis of chemical allergenicity. Chemical allergy refers to an allergic reaction to a low molecular weight agent (ie, <1 kD). The symptoms and pathology of chemical asthma resemble those of allergy to larger sized agents, such as pollens, weeds, and danders. The differences relate to mechanisms of disease. To stimulate an immune response, low molecular weight chemicals function as haptens and bind to carrier macromolecules. This article focuses on the chemical reactions and physicochemical characteristics of chemical allergens. DATA SOURCES: Data were obtained from published clinical reports and from the Documentation of Threshold Limit Values (1998) published by the American Congress of Governmental Industrial Hygienists. RESULTS: In vitro studies indicate the stoichiometric reaction of some chemical allergens with glutathione and the subsequent transfer of the allergen from glutathione to other nucleophiles. Computer-generated structure activity relationship models have been developed for chemicals that induce respiratory allergy. The models, based on physicochemical properties of the agents, have high sensitivity and specificity. CONCLUSIONS: The structure activity relationship model suggests that chemical binding is the essential feature of chemical allergens. Their in vivo reactions with thiols may result in glutathione deficiency with consequent alteration in cellular reduction-oxidation (redox) status, release of cytokines, and promotion of the T helper cell 2 phenotype. Prevention of permanent disease is dependent on periodic medical surveillance of affected workers. When detected early, the disease can frequently be reversed. PMID- 11770681 TI - Indoor pollution and its impact on respiratory health. AB - LEARNING OBJECTIVES: This overview discusses the respiratory complications of indoor air pollution, emphasizing the most common pollutants that individuals are likely to encounter outside the workplace. DATA SOURCES: Data were obtained from a review of the recent literature. STUDY SELECTION: The expert opinion of the author was used to select and synthesize relevant data on this multifaceted subject. RESULTS: There have been a number of studies documenting an association between exposure to indoor allergens and development of both sensitization and asthma in children. In addition to classic allergens, chemical indoor air pollution may also exert an adverse effect on both the upper and lower respiratory tract by a variety of nonimmunologic, irritative mechanisms. CONCLUSIONS: Our understanding of the adverse effects of indoor air pollution on health and comfort has broadened in recent years. It has supplied a credible framework for developing and implementing a variety of control strategies. PMID- 11770682 TI - Do air cleaners make a difference in treating allergic disease in homes? AB - LEARNING OBJECTIVES: The purpose of this review is to objectively critique available data regarding the clinical benefits of room air cleaners and to provide physicians and patients with a reasonable recommendation of their utility in treatment of inhalant allergic disease. DATE SOURCES: Data were obtained from published studies and reviews. STUDY SELECTION: The specific reviewed studies met the following criteria: 1) selection of patients with clinical allergic disease confirmed by detection of allergen-specific immunoglobulin E; 2) use of an effective air filter; 3) clinical and laboratory evaluation of results; and 4) measurement of the results of air filtration on environmental allergen or airborne particulate levels. The studies were conducted in a double-blind manner. Conclusions of two previous reviews are also incorporated in this paper. RESULTS: The results of the published studies and summary reviews show minimal, if any, effectiveness of room air cleaners in treatment of allergic respiratory disease. CONCLUSIONS: Room air cleaners should not be recommended for people with inhalant allergic disease. PMID- 11770683 TI - Methods and effectiveness of indoor environmental control. AB - LEARNING OBJECTIVES: The purpose of this review is to describe recommended methods of decreasing exposure to indoor allergens. DATA SOURCES: Data were obtained from published studies and reviews. STUDY SELECTION: The reviewed studies met these criteria: 1) measurement of environmental allergens; 2) selection of participants with clearly defined allergic airway disease confirmed by detection of allergen-specific immunoglobulin E; and 3) clearly defined clinical and environmental outcomes. The studies were conducted as controlled clinical trials and the results between treated and control groups were compared with appropriate statistics. RESULTS: The results of these studies show that installing allergen proof encasings and washing bedding frequently reduces house dust mite exposure by 10-fold or more and significantly improves clinical measures of asthma. Washing pets reduces allergen levels temporarily. Excluding the pet from the bedroom while installing allergen-proof encasings and operating air cleaner reduces airborne allergens although having no significant effect on allergic symptoms. Cockroach populations can be controlled for over 6 months and allergens can be reduced with controlled pesticide application and cleaning, but clinical correlates have not been reported. Methods to improve adherence to environmental control measures have not been tested but effective methods can be recommended from literature on medication adherence. CONCLUSIONS: For patients allergic to indoor allergens, reasonable recommendations include installation of allergen-impermeable encasings, frequent laundering of bedding, removing furred pets from the home, and controlling of cockroach populations with effective pesticides using the principles of integrated pest management. PMID- 11770684 TI - The heterogeneity of allergic phenotypes: genetic and environmental interactions. AB - OBJECTIVE: This article reinforces the reader's knowledge of the multifactorial nature of allergic diseases and of the heterogeneity of allergic phenotypes. DATA SOURCES: Personal studies and an evidence-based approach is used to support the assumption that three major abnormalities concur in the pathophysiology of allergic diseases: 1) enhanced allergen recognition and specific immune response; 2) a T helper 2 cytokine profile that results in polyclonal immunoglobulin E activation and mast cell-eosinophilic inflammation; and 3) organ hyperreactivity. STUDY SELECTION: Examples of genetic and environmental factors that preferentially influence each of these distinct pathophysiologic abnormalities are provided. RESULTS: Data presented indicate that allergic diseases distribute along a wide spectrum depending on the preferential pathophysiologic abnormalities operating in the individual patient. CONCLUSIONS: Categorization of allergic patients into distinct clinical phenotypes might result in a more patient-oriented (rather than disease-oriented) approach, and hence, better management. PMID- 11770685 TI - Fungi: toxic killers or unavoidable nuisances? AB - OBJECTIVES: This discussion is focused on the many roles of fungi in human health, and also to put the mycotoxin literature into perspective. DATA SOURCES: Data are derived from the literature referenced in PubMed from the National Library of Medicine, earlier references in the authors' reprint collection, and ongoing research. Studies for review were either selected from the peer-reviewed literature or from standard texts that are well recognized in the field. RESULTS: The review yielded many studies of the role of fungi in allergic disease, but none that systematically documented such a role for mycotoxins or fungal volatiles. Many case studies were found, but none of these unequivocally document a cause/effect relationship between mycotoxin exposure by inhalation and human disease in residential, school, or office settings. CONCLUSIONS: The review led to the conclusion that that the primary result from fungal exposure is allergic disease, and that the evidence for inhalation disease resulting from mycotoxin exposure in residential and office settings is extremely weak. PMID- 11770686 TI - Stachybotrys: relevance to human disease. AB - LEARNING OBJECTIVES: Recent public concern about the danger of environmental fungi has focused attention on one particular mold, Stachybotrys. The purpose of this review is to examine and critique the published literature on Stachybotrys for objective scientific and clinical evidence of disease caused by the presence of this fungal organism in the environment. DATA SOURCES: Data were obtained from all published research and reviews of Stachybotrys indexed in MEDLINE since 1966. STUDY SELECTION: The publications used for this review were those that contained information about human health effects of this microorganism. The critique of these publications is the author's. RESULTS: Stachybotrys is a minor component of the indoor mycoflora, found on certain building material surfaces in water damaged buildings, but airborne spores are present in very low concentrations. Published reports fail to establish inhalation of Stachybotrys spores as a cause of human disease even in water-damaged buildings. A possible exception may be mycotoxin-caused pulmonary hemorrhage/hemosiderosis in infants, although scientific evidence to date is suggestive but not conclusive. Based on old reports ingestion of food prepared from Stachybotrys-contaminated grains may cause a toxic gastroenteropathy. No convincing cases of human allergic disease or infection from this mold have been published. CONCLUSIONS: The current public concern for adverse health effects from inhalation of Stachybotrys spores in water-damaged buildings is not supported by published reports in the medical literature. PMID- 11770687 TI - Environmental factors as a cause for the increase in allergic disease. AB - LEARNING OBJECTIVES: To be able to understand the interaction among genetic factors, environmental exposure to allergens, and nonspecific adjuvant factors contributing to the increase in atopic diseases in developed countries. DATA SOURCES: Peer-reviewed literature identified by searching medical databases. STUDY SELECTION: Careful review of epidemiologic cross-sectional, sequential, and longitudinal population studies and, when appropriate, intervention studies. The criteria used to accept a study reporting environmental factors influencing the prevalence of allergic diseases were adopted from the report published by the US Department of Health and Education in 1964 (Hill AB, Principles of Medical Statistics, 9th Ed. New York: Oxford University Press, 1971, p. 323) RESULTS: There is ample evidence that specific environmental factors may cause sensitization and development of allergic symptoms and disease in susceptible individuals. It is unclear when and how long a sufficient exposure will result in clinical symptoms related to the immunoglobulin E-sensitizing agents. CONCLUSIONS: Environmental factors play an important role for the development and manifestation of allergic conditions in genetically predisposed subjects. It is well documented that increased exposure to indoor allergens and selected outdoor allergens (eg, grass pollen and molds) and smoking are important risk factors for development of asthma and allergic sensitization. The importance of other environmental factors is less clear and which environmental factors that cause the increase in prevalence of allergic disease is still unknown. PMID- 11770688 TI - Food allergy and quality of life issues. PMID- 11770689 TI - When the whole is more than the sum of its parts. PMID- 11770690 TI - Management of influenza in patients with asthma or chronic obstructive pulmonary disease. AB - OBJECTIVE: To review the prevention and treatment of influenza in patients with asthma and/or chronic obstructive pulmonary disease (COPD). DATA SOURCES: Computer-assisted MEDLINE searches for article and manual searches of conference proceedings on influenza, influenza vaccination, rimantadine, amantadine, oseltamivir, zanamivir, asthma, and/or COPD. STUDY SELECTION: Published articles and pertinent conference abstracts in the areas mentioned in Data sources were selected. Articles included for review were studies conducted on humans. RESULTS: Annual vaccination against influenza is the currently accepted practice for influenza management in patients with asthma and/or COPD. However, despite the availability and use of vaccination, influenza continues to cause serious morbidity and increased mortality. The management of influenza in at-risk patients with the older antivirals such as amantadine or rimantadine has not been widely accepted because of the rapid emergence of resistant variants, their lack of effect against influenza B, and poor adverse event profile. A new class of influenza antivirals, the neuraminidase inhibitors, has recently become available for the management of influenza. The currently marketed neuraminidase inhibitors are zanamivir and oseltamivir. Clinical studies have shown that these neuraminidase inhibitors are effective for the treatment and chemoprophylaxis of influenza A and B. CONCLUSIONS: Vaccination against influenza remains the gold standard for the prevention of influenza in patients with asthma and/or COPD. The neuraminidase inhibitors zanamivir and oseltamivir are useful adjuncts to influenza vaccines for the management of influenza in these patients who are at high-risk of developing influenza related complications. PMID- 11770691 TI - Urticaria, angioedema, and an elevated eosinophil count in an adolescent. PMID- 11770692 TI - The impact of childhood food allergy on quality of life. AB - BACKGROUND: Food allergy affects >6% of children, but the impact of this disease on health-related quality of life has not been well studied. METHODS: Parental perceptions of physical and psychosocial functioning were measured with the Children's Health Questionnaire (CHQ-PF50). This tool and an additional allergy related questionnaire were sent to 400 members of the Food Allergy and Anaphylaxis Network with children aged 5 to 18, an age group on which the tool has been validated. RESULTS: Surveys were completed by 253 parents (63%). The mean age of the food-allergic children was 10.8 years (range, 5 to 18 yrs); 59% were male. Sixty-eight percent were allergic to one or two foods, the remainder to more than two foods. Concomitant chronic atopic diseases included: asthma with atopic dermatitis (33%), atopic dermatitis alone (13%), asthma alone (33%), and 21% had neither asthma nor atopic dermatitis. In comparison to previously established norms, the families scored significantly lower (more than 10 scale score points lower and P < 0.0001) for general health perception (GH), emotional impact on the parent (PE), and limitation on family activities (FA). Associated atopic disease, influenced primarily by those with both asthma and atopic dermatitis, accounted for a significant reduction in the GH scale (analysis of variance, P = 0.0001), but not for measures of PE and FA. Within the study group, food-allergic individuals with several (more than two) food allergies had significantly lower (P < 0.05) scores for 7 of 12 scales compared with individuals with few (one or two) food allergies. However, those with one or two food allergies scored significantly lower (P < 0.0001) than established norms on scales for GH, PE, and FA. CONCLUSIONS: Childhood food allergy has a significant impact on GH, PE, and FA. Factors that influence reductions in these scales include associated atopic disease and the number of foods being avoided. PMID- 11770693 TI - Salmeterol 100 microg: an analysis of its tolerability in single- and chronic dose studies. AB - BACKGROUND: A combination product containing fluticasone propionate 100 or 250 microg and salmeterol 50 microg has recently been made available in the United States. Some patients, if previously instructed to double their inhaled corticosteroids, may double this product, inadvertently receiving higher doses of salmeterol, potentially causing systemic beta2-agonist-related effects. OBJECTIVES: To examine the systemic effects of single and chronic doses of salmeterol 100 microg. METHODS: Forty-four studies including a salmeterol 100 microg treatment arm were identified. Data on predictable systemic effects were available in 10 single-dose and 9 chronic-dose studies lasting more than 7 days, in patients with asthma (6 adult, 2 pediatric) or chronic obstructive pulmonary disease (1 study), which were included in a weighted, pooled analysis. RESULTS: Single 100-microg dose studies: mean change from baseline in heart rate was +2.3 beats per minute and systolic blood pressure +0.4 mm Hg. Tremor and palpitations were reported in 5.7% and 2.8%. Other systemic effects included a decrease in serum potassium for 3 subjects (2.1%); an increase in serum glucose, 1 subject (0.7%); and electrocardiographic (ECG) events, 24 cases (17.0%). Twenty-three of these were from one crossover study which reported 27 ECG events after placebo. Chronic dose studies (salmeterol 100 microg): mean change in heart rate and systolic blood pressure were +1.8 beats per minute and -0.2 mm Hg. Tremor and palpitations were reported in 5.6% and 1.7% of 1,504 patients. Thirteen recorded a decrease in serum potassium (0.9%) and 5 an increase in serum glucose (0.3%). Nine patients had ECG events (0.6%). Eight of these were "arrhythmia" from one study, which also reported 12 events before treatment. CONCLUSIONS: The mean systemic effects of salmeterol 100 microg are small and of doubtful clinical relevance. Patients (and their caregivers) can be reassured that inadvertently taking double doses of the new combination product are unlikely to affect them adversely. PMID- 11770694 TI - Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with seasonal allergic rhinitis: confirmation of a test system. AB - BACKGROUND: The environmental exposure unit (EEU) is an instrument designed to determine onset of action of antiallergic treatment. Confirmation of test results would be useful in defining its role. OBJECTIVE: This study was intended to confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU using an identical protocol design (randomized, double-blind, parallel-group comparison having the same symptom scoring system, endpoints, and statistical analyses), thus demonstrating reproducibility of studies conducted in the EEU. METHODS: Onset of action and symptom relief with once-daily cetirizine 10 mg, loratadine 10 mg, and placebo (n = 120 each group) were evaluated replicating a previous study design. Subjects meeting inclusion and exclusion criteria and qualifying symptom scores were randomized to 2 days' exposure (6 to 7 hours daily) with treatment. Changes in total and major symptom complex (TSC, MSC) scores based on 14 symptoms evaluated at 30-minute intervals served as primary efficacy variables. RESULTS: Onset of action again was earlier with cetirizine (at 1 hour, P < or = 0.001) versus loratadine (at 3 hours, P < or = 0.01). Cetirizine produced a 25.4% least-square mean reduction in TSC scores overall versus an 11.2% decrease with loratadine (P = 0.006) and a 4.8% increase with placebo (P < 0.001); loratadine and placebo were also significantly different (P = 0.002). Similar changes were also noted in MSC scores. Cetirizine consistently reduced TSC and MSC scores after the first dose versus placebo (P < or = 0.001) and at most time points versus loratadine (P < or = 0.05). Adverse events were reported in 1.7% of patients in each active-treatment group and in 2.5% on placebo. CONCLUSIONS: Cetirizine acted earlier and was more effective than loratadine or placebo in reducing symptoms of seasonal allergic rhinitis in subjects undergoing a controlled pollen challenge, replicating results from an earlier, identically designed study, demonstrating reproducibility of these assessments by the EEU. PMID- 11770695 TI - Evaluation of particle size distribution of salmeterol administered via metered dose inhaler with and without valved holding chambers. AB - BACKGROUND: Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask. OBJECTIVE: This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs. METHODS: Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus. RESULTS: Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 microm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated. CONCLUSIONS: In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone. PMID- 11770696 TI - Once-daily budesonide inhalation suspension in infants and children < 4 and > or = 4 years of age with persistent asthma. AB - BACKGROUND: Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. OBJECTIVE: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma. METHODS: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic pituitary-adrenal-axis function. RESULTS: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level. CONCLUSIONS: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age. PMID- 11770697 TI - Effect of experimental influenza A infection on systemic immune and inflammatory parameters in allergic and nonallergic adult subjects. AB - BACKGROUND: The economic impact and medical complication rate of viral upper respiratory infections are well documented, but many of the physiologic, inflammatory, and immune responses to respiratory viruses have only recently been investigated. A previous study demonstrated differential systemic immune and inflammatory responses in allergic rhinitis (AR) and nonallergic rhinitis (NAR) subjects during experimental infection with rhinovirus-39. OBJECTIVE: The purpose of this study was to compare selected systemic immune and inflammatory responses to experimental influenza A virus (FLU) challenge in seronegative AR and NAR subjects. METHODS: Peripheral blood was obtained at baseline (study day 0) and 3, 6, 18, and 31 days after intranasal FLU challenge and assayed for leukocyte histamine release, serum immunoglobulins, and plasma histamine. RESULTS: All subjects were infected, as manifested by viral shedding in nasal secretions and/or seroconversion. FLU infection induced decreases in spontaneous leukocyte histamine release and increases in anti-immunoglobulin E-induced leukocyte histamine release, which were evident at least 1 month after infection, but caused no significant changes in serum immunoglobulins or plasma histamine. There were no differences between AR and NAR subjects for any of the study parameters. CONCLUSIONS: The results show that intranasal challenge with FLU induces changes in leukocyte histamine release, but not other systemic immune and inflammatory responses. PMID- 11770698 TI - Clarithromycin potentiates glucocorticoid responsiveness in patients with asthma: results of a pilot study. AB - BACKGROUND: Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects. OBJECTIVE: To determine whether clarithromycin, by virtue of its anti inflammatory effects, enhances glucocorticoid sensitivity. DESIGN: Open-label, pilot study in a paired design (pre- and posttreatment). PARTICIPANTS: Seven patients, mean age 27 (range 15 to 42 years), with mild to moderate asthma under good control. METHODS: Clarithromycin (500 mg) was administered twice daily for 10 days with blood drawn for lymphocyte stimulation assays at baseline, and again upon completion of therapy. Lymphocytes were stimulated with phytohemagglutinin in the presence and absence of increasing concentrations of clarithromycin and dexamethasone (DEX). RESULTS: At baseline, clarithromycin alone did not cause a significant degree of suppression of T-lymphocyte activation, yet clarithromycin significantly enhanced the sensitivity of lymphocytes to suppression by DEX as measured by a shift in the DEX dose-response curve by at least 6-fold (P = 0.04). In addition, a 10-day course of clarithromycin resulted in: 1) a significant decrease in the inhibitory concentration which results in a 50% reduction in proliferation for DEX alone, thereby increasing glucocorticoid sensitivity (P = 0.04); 2) heightened inhibitory effect of clarithromycin alone (P = 0.03); and 3) a sustained suppressive effect with the combination of clarithromycin and DEX on the inhibition of lymphocyte stimulation (P = 0.01). CONCLUSIONS: Clarithromycin acts synergistically with DEX in suppressing lymphocyte activation. In addition, a 10-day course resulted in a significant treatment effect as evidenced by lower inhibitory concentration which results in a 50% reduction in proliferation value for DEX, a heightened response to clarithromycin alone, and a consistent degree of suppression of lymphocyte stimulation when clarithromycin and DEX were used together. PMID- 11770699 TI - LTC4-synthase A-444C polymorphism: lack of association with NSAID-induced isolated periorbital angioedema in a Spanish population. AB - BACKGROUND: The mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced reactions is unknown. However, strong evidence supports the hypothesis of an enhanced production of cysteinyl-leukotrienes. The existence of a polymorphism (A 444C) in the promoter region of the leukotriene (LT)C4-synthase gene (the terminal enzyme in the LTC4 production pathway) has been reported. This polymorphism has yielded contradictory results on its association with aspirin induced asthma. OBJECTIVE: The present study was designed to investigate the possible genetic association of C(-444) allele and a specific clinical phenotype of NSAID sensitivity, the NSAID-induced isolated periorbital angioedema, via a case/control study. METHODS: The polymorphism A-444C was analyzed in 58 patients with NSAID-induced periorbital angioedema and 61 control subjects, who had undergone single-blind, placebo-controlled oral challenge. Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We have not found an association of C(-444), allele with NSAID-induced isolated periorbital angioedema. CONCLUSIONS: Further studies are needed to determine whether polymorphisms in the LTC4-synthase gene or other leukotriene forming enzymes are involved in the pathogenesis of the different subsets of NSAID sensitivity. PMID- 11770700 TI - Dermatophagoides pteronyssinus. PMID- 11770701 TI - Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. AB - To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting. PMID- 11770702 TI - Anticancer activity of mycobacterial DNA: effect of formulation as chitosan nanoparticles. AB - Mycobacterium phlei (M. phlei) DNA inhibits cancer cell division but is susceptible to degradation by DNase. Chitosan forms nanoparticulate polyelectrolyte complexes with DNA, and may thus reduce nuclease degradation. We have characterized chitosan-DNA nanoparticle formation, determined DNase susceptibility, and evaluated their antiproliferative activity. Nanoparticle diameter initially decreased with increasing phosphate charge density. However nanoparticle diameter increased above 6 micromol of phosphate. Particle aggregation occurred at 16.2 micromol phosphate and was related to reduced surface charge. Incorporation of DNA within chitosan nanoparticles significantly decreased degradation by DNase. The ability of M. phlei DNA-chitosan nanoparticles to inhibit melanoma cell division was determined relative to M. phlei DNA and a cationic liposomal M. phlei DNA formulation. M. phlei DNA had antiproliferative activity (MTT reduction, IC50 = 0.9 mg/ml) without intrinsic cytotoxicity (LDH release, ED50 > 50 microg/ml). Cationic polyphosphate chitosan nanoparticles were inert (antiproliferative IC50 > 1 mg/ml, ED50 > 1 mg/ml). M. phlei DNA-chitosan nanoparticles were 20-fold more potent than M. phlei DNA. Cationic DOTAP/DOPE liposomes were cytostatic (IC50 = 49 microg/ml) and cytotoxic (ED50 = 87 microg/ml), and complexation of M. phlei DNA resulted in a significant reduction of antiproliferative activity. Chitosan nanoparticles may therefore be appropriate delivery vehicles for M. phlei DNA. PMID- 11770703 TI - Treatment-induced expression of anti-apoptotic proteins in WSU-CLL, a human chronic lymphocytic leukemia cell line. AB - Bryostatin 1 (bryo 1) has been shown to potentiate the anti-tumor activity of 2 chloro-2-deoxyadenosine (2-CdA) in chronic lymphocytic leukemia (CLL) and in the WSU-CLL cell line. However, like resistant CLL, WSU-CLL cells lose their sensitivity to bryo 1/2-CdA treatment. We report that 2-CdA-induced IAP expression may be a possible mechanism whereby resistance to apoptosis is acquired in these cells. In WSU-CLL cells, three members of the Inhibitors of Apoptosis (IAP) family were identified. Bryo 1 treatment of WSU-CLL cells leads to initiation of the apoptotic cascade and induced a marginal increase in XIAP protein expression. In contrast, 2-CdA treatment, alone or in combination with bryo 1, induced a substantial increase in survivin and XIAP proteins and phosphorylation of BAD. Bryo 1 alone induced caspase-7 and -9 dependent [poly ADP ribose] polymerase (PARP) cleavage, while sequential treatment with bryo 1 (72 h) followed by 2-CdA (24 h) induced caspase-3,-7, and -9 dependent PARP cleavage and increased apoptosis. Although exposure to bryo 1 initiated apoptotic events, apoptosis was first enhanced by 2-CdA, and then reversed in a time-dependent manner by 2-CdA-induced expression of survival proteins. Taken together, resistance to bryo 1/2-CdA treatment may be the result of 2-CdA-induced IAP inhibition of the intrinsic apoptotic pathway caspases. PMID- 11770704 TI - Pharmacokinetic analysis of lectin-dependent biodistribution of fucosylated bovine serum albumin: a possible carrier for Kupffer cells. AB - To examine the potential utility of fucosylation of drug carriers for targeted drug delivery to Kupffer cells, the pharmacokinetics of (111)In-labeled fucosylated bovine serum albumin (Fuc-BSA) with different numbers of fucose residues (11, 16, 25, 31 or 41) was studied. After intravenous injection in mice, all (111)In-Fuc-BSAs were mainly delivered to the liver and their hepatic uptake became saturated when the dose was increased. Of these derivatives, only (111)In Fuc41-BSA showed a slow plasma elimination at low doses, suggesting an interaction with blood components. Examination of binding conditions as well as electrophoretic analysis of the binding components indicated that the serum-type mannan binding protein (MBP) is responsible. Kupffer cells, which possess fucose receptors, showed the highest uptake of (111)In-Fuc41-BSA, followed by endothelial cells and hepatocytes. The hepatic uptake of (111)In-Fuc41-BSA was inhibited by co-injection of Gal42-BSA, but not by Man46-BSA. On the other hand, excess Fuc41-BSA inhibited the hepatic uptake of (111)In-Man46-BSA, while (111)In Gal42-BSA did not: These findings suggest that not only the fucose receptors on Kupffer cells but also other lectins are involved in the biodistribution of Fuc BSAs. To understand how the degree of fucose modification affects the binding affinity of Fuc-BSA with hepatic lectins and serum MBP, a pharmacokinetic analysis was performed based on a physiological model. The Michaelis constant of the hepatic uptake of (111)In-Fuc-BSA decreased with an increasing number of fucose units, and the intrinsic hepatic clearance of (111)In-Fuc25-, (111)In Fuc31- and (111)In-Fuc41-BSAs was close to, or much greater than, the hepatic plasma flow rate, indicating efficient hepatic uptake of these derivatives. These results suggest that fucosylation is a potentially useful method making drug carriers selective for Kupffer cells, although extensive modification might result in retarded delivery due to binding to other lectins like MBP. PMID- 11770705 TI - Effect of injection volume on the pharmacokinetics of oil particles and incorporated menatetrenone after intravenous injection as O/W lipid emulsions in rats. AB - Oil-in-water lipid emulsions are promising drug carriers for lipophilic drugs, however, the pharmacokinetics after entering the circulation should be clarified at clinical injection volume in order to utilize them in a clinical situation. In the present study, the standard lipid emulsions, consisting of soybean oil, egg yolk phosphatides and menatetrenone with diameters of about 150 nm, were prepared using a microfluidizer system. The pharmacokinetics of menatetrenone and the oil particles after intravenous injection as standard lipid emulsions at various injection volumes, from the clinical injection volume (0.1 ml/kg) to the experimental injection volume (3.0 ml/kg), were examined in rats. The plasma concentrations of menatetrenone and the oil particles were similar after administration, showing that menatetrenone was not released even after entering the circulation. Menatetrenone was delivered to the liver and spleen at the clinical injection volume, and more menatetrenone was delivered to the liver at clinical injection volume compared with the experimental volume. Moreover, additional information on injection volume-dependency was also obtained from these findings. These results at various injection volumes suggested that the standard lipid emulsions can be utilized as a useful drug delivery system at the clinical injection volume, especially for liver and spleen targeting. PMID- 11770706 TI - Polylactide-poly(ethylene glycol) micellar-like particles as potential drug carriers: production, colloidal properties and biological performance. AB - The micellar-like particle systems produced from poly-D,L-lactide-poly(ethylene glycol) (PLA-PEG) copolymers have been assessed using a range of physicochemical characterisation methods, followed by in vivo studies of their biodistribution after intravenous administration to the rat. The size of the PEG chain was kept constant at 5 or 2 kDa, while the PLA size increased within a series from 2 to 25 kDa. The results obtained reveal, that in an aqueous medium the copolymers assembled into micellar-like structures, with the PLA segments forming the core and the PEG segments the surrounding corona. The size of the PLA segments dominated the process of assembly of the molecules and the characteristics of the resultant micellar-like particles. The PLA-PEG micellar particles were found to be less dynamic than those obtained from conventional surfactants. Particles formed from the lower molecular weight PLA polymers allowed a level of chain mobility while the cores of the micellar particles formed from higher molecular weight PLA appeared to be solid-like in nature. The size of the micellar particles was dependent on the copolymer molecular weight and the z-average diameter increased from 25 to 76 nm as the molecular weight of the PLA moiety increased. This provides an ability to control the particle size by adjusting the molecular weight of the PLA moiety. Following intravenous administration to the rat model, micellar-like particles smaller than approximately 70 nm accumulated in the liver, despite the fact that the PEG corona provided an effective steric stabilization effect. Micellar-like particles with a diameter of more than approximately 70 nm exhibited prolonged systemic circulation and reduced liver uptake, although the steric stabilisation of these particles was shown to be less effective. These findings agree with recent observations from other research groups; that indicate a possibility that very small particulates can pass through the sinusoidal fenestrations in the liver and gain access to the parenchymal cells of the liver. PMID- 11770707 TI - Biomembrane model interaction and percutaneous absorption of papaverine through rat skin: effects of cyclodextrins as penetration enhancers. AB - The effects of different concentrations of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-di-O-methyl-beta cyclodextrin (DM-beta-CyD) on percutaneous absorption of papaverine hydrochloride (PAP) were investigated. Abdominal rat skin mounted in Franz cells was used for in vitro experiments. To evaluate CyD interaction with a bilayer structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC-Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evaluated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-beta-CyD shows higher enhancer activity as a possible result of a perturbing action on the skin by a complexation of its lipid components, but at higher concentrations HP-beta-CyD is the most effective. By considering that HP-beta-CyD presents a very moderate destabilizing action on the skin, we conclude that a 10% aqueous solution of this macrocycle appears to be the most suitable transdermal absorption enhancer for PAP. PMID- 11770708 TI - A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE). AB - Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11 13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease. PMID- 11770709 TI - Effect of ethyl icosapentaenoate (EPA) on the concentration of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in the carotid artery of cuff-sheathed rabbit models. AB - To evaluate the effect of ethyl icosapentaenoate (EPA) on the metabolism of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta), the concentrations of these cytokines in the carotids of rabbits sheathed in a cuff were studied. Japanese white rabbits were divided into two groups; the EPA group, in which 600 mg/kg/day EPA was administered forcibly p.o. for 1 week before cuff treatment, and the control group. Carotid artery samples were obtained just before, 3 days and 7 days after cuff treatment, and TNFalpha and IL-1beta were determined separately with the Western blot analysis method. In the control group, there were 43.5 (+/- 3.0) pg/microg protein of TNFalpha and 53.5 (+/- 4.8) pg/microg protein of IL-1beta just before cuff treatment. Compared to the control group, these concentrations of the EPA group were both significantly low. Three days after cuff treatment, TNFalpha of the EPA group was still significantly low, while IL-1beta showed no difference. There was no significant difference between the two groups 7 days after cuff treatment. These findings suggested that EPA could influence TNFalpha and IL-1beta metabolism in the arterial wall even at baseline. Furthermore, EPA suppressed TNFalpha and IL-1beta production in the early phase of intimal thickening, indicating a mechanism inhibiting the activation of smooth muscle cells such as their proliferation and migration, induced by the cuff-sheath method. PMID- 11770710 TI - Expression of matrix metalloproteinase 3 in experimental atherosclerotic plaques. AB - In atherosclerotic lesions, matrix metalloproteinases produced by foam cells (macrophages) are thought to increase plaque instability, promote plaque rupture, by degradating extracellular matrix. To investigate the relationship between the expression of these proteinases and the histologic appearance of atheromas, immunohistochemical analysis of matrix metalloproteinase 3 and cell-type markers was performed in atherosclerotic plaques induced in rabbit abdominal aortas by high-cholesterol diets and mechanical injury. In addition to an antibody against matrix metalloproteinase 3, RAM-11 and HHF-35 were used to detect macrophages and smooth muscle cells, respectively. Matrix metalloproteinase 3 was expressed diffusely within the plaques with a fibrofatty histologic pattern. In plaques with foam cell accumulation, matrix metalloproteinase 3 was seen in areas rich in foam cells and the smooth muscle cells near the lumen. In the plaques with fewer macrophages, the proteinase was expressed only in such smooth muscle cells. Matrix metalloproteinase 3 was expressed in the smooth muscle cells in plaques of all histologic types, and macrophages also expressed the metalloproteinase when present in significant numbers. These findings suggest that macrophage accumulation plays an important pathophysiologic role in causing the instability of atherosclerotic lesions by increasing the levels of matrix metalloproteinase 3. PMID- 11770711 TI - Effect of glucose concentration on foam cell formation in THP-1 cells. AB - We investigated whether a high glucose condition could affect cholesterol ester (CE) synthesis and accumulation of cholesterol in arterial wall cells by using the human monocytic cell line THP-1. After 24-hour PMA treatment, cells were grown in control (200 mg/dl of glucose) or high glucose concentration (400, 600, 800, or 1,600 mg/dl) medium for 6 days. CE synthesis was then investigated in cells incubated with 50 microg/ml of native, glycated, acetylated, or oxidized LDL. Cells grown in 400 mg/dl of glucose showed a significant increase of CE synthesis regardless of whether they were incubated with native, glycated or oxidized LDL, compared with cells grown in 200 mg/dl of glucose. In parallel with the studies of CE synthesis, the intracellular accumulation of CE also increased in cells grown in 400 mg/dl of glucose when incubated with oxidized LDL (50 microg/ml), compared with that in cells grown in 200 mg/dl of glucose. The amount of oxidized LDL associated with cells grown in 400 mg/dl of glucose was markedly higher than that in cells grown in 200 mg/dl of glucose. This suggests that there is an optimal glucose concentration (400 mg/dl) which increases the number of some scavenger receptors (receptors for oxidized LDL) expressed on cells, and might increase and stimulate CE synthesis, resulting in intracellular accumulation of CE in macrophage. A high blood glucose concentration could change the metabolism of arterial wall cells and play an important role in the pathogenesis of vascular complications of diabetes mellitus. PMID- 11770712 TI - Skin, sun, and vitamin A: from aging to cancer. AB - Human epidermis contains significant amounts of Vitamin A, the enzymes responsible for its metabolism toward either storage or activation, the binding proteins for its protection and specific transport, and the nuclear receptors involved in the vitamin A-induced gene-activity modulation. This complex system may be drastically altered upon ultraviolet light exposure because vitamin A absorbs in the UVB range. We have conducted a series of experiments in order to analyse the effects of UV exposure on the epidermal stores of endogenous vitamin A (retinol and retinyl esters), the activity of enzymes and binding proteins, and some biological parameters such as apoptosis transcription factors expression (cJun) and thymine dimers. Current data indicate that the vitamin A system is a direct target of both UVB and UVA and participates in an adaptive response to UV exposure. The physiological role of this adaptive response to acute and chronic sun exposure should be further analysed. Interfering with this UV-induced vitamin A deficiency is a new concept for the prevention of skin cancer and aging. PMID- 11770713 TI - Dermatological research in the 21st century: our fantastic future. AB - During the second half of the twentieth century, dermatology came of age. Just as clinical dermatology, through new diagnostic and therapeutic modalities, matured to a point where the dermatologist could affect peoples' lives profoundly, so too did dermatological research enhance our understanding of skin diseases enormously. Dermatology should not be viewed as a scientific discipline-advances come from fundamental scientific areas such as cell and molecular biology, biochemistry, immunology, microbiology, technology, the clinical sciences and others. Thus, dermatology and skin biology live within a universe of science, only a small part of which is dermatology and skin biology, and our patients and our science are dependent on integration and interdigitation with the universe of science for future success. In this lecture I will elaborate on where I think the next 10-20 years will take us in this universe. PMID- 11770714 TI - The public health approach to the burden of common skin diseases in the community. AB - The vast majority of work performed by dermatologists in clinical practice is managing common skin conditions including eczema, psoriasis, acne, tinea, warts and in some countries skin cancer and in others skin infections. Governments and other health organisations rely on data to plan medical services. Dermatologists seek the same data to justify their existence. In Australia, we have been studying the frequency of these conditions showing that they are very common, with particular conditions occurring at particular ages. Our data show also that less than 50% of people seek advice from the medical practitioner, with pharmacists being the most common of the other sources of advice. People are frequently misinformed about their conditions and may be using treatment that is of no value. These data suggest the need for both public and professional education programs informing the public where to seek correct advice and teaching those who provide it to ensure that they have the knowledge to do so. PMID- 11770715 TI - Tumor biology in cutaneous malignant lymphomas. PMID- 11770716 TI - Clinical spectrum of Behcet's disease. AB - Behcet's disease is a chronic systemic inflammatory disease involving mucous membranes, skin, eyes, the gastrointestinal tract, joints, blood vessels, and the neurologic system. Behcet's disease occurs endemically in the Middle East and Mediterranean regions. It is also distributed in the Central and Far Eastern Asian countries including Korea, Japan, and China. With the volume of clinical information obtained from over 5,000 patients who visited the Behcet's Disease Specialty Clinic, Severance Hospital, Yonsei University College of Medicine, informative and educational viewpoints of Behcet's disease including dermatologic and other systemic manifestations were introduced. PMID- 11770717 TI - Cutaneous photodamage in Asians. PMID- 11770718 TI - Traveling through skin manifestations of HIV in 2001. AB - There are currently over 34 million people worldwide infected with human immunodeficiency virus (HIV) with 15,000 new patients infected each day. The acquired immunodefiency syndrome (AIDS) pandemic has particularly affected the third world and currently over 70% of those infected reside in sub-Saharan Africa. The epicenter of the pandemic is shifting to Asia as HIV infection increases in the densely populated countries of India, China, and SE Asia. Patients with HIV infection develop a variety of mucocutaneous diseases and often present to dermatologists. PMID- 11770719 TI - Great cases from the University of Pennsylvania. AB - New skin diseases are reported yearly. Some well-known conditions may develop unusual manifestations. Other cutaneous findings are simply rare. While patients with such diseases represent only a small fraction of our practice they are an important subset of our experience. Many of these diseases are treatable, pinpoint the discovery of internal disease, or simply allow for a diagnosis and prognosis to be given to a concerned patient who had previously escaped classification. Such cases expand our knowledge and provide excitement to our day. Several patients from whom I have learned the most in the last few years are detailed for your enjoyment. PMID- 11770720 TI - Environmental and occupational skin diseases in Taiwan. AB - This presentation focuses on the four most important skin diseases in Taiwan thought to be of environmental and/or occupational origin. The majority of work related dermatoses are contact dermatitis patients. Among occupational contact dermatitis patients, 58.5% involved irritant and 41.5%, allergic dermatitis. Electronics, hairdressing, medical practice, and construction were the most important occupations causing contact dermatitis. An endemic occurrence of chronic arsenism causing hyperpigmentation, keratosis, and cancer has been reported in Taiwan. Arsenical skin cancers present as multiple lesions at different disease stages. The skin cancers are usually found in non-sun-exposed areas. UVB exerts an inhibitory effect on the proliferation of arsenical cancers; this may explain its non-sun-exposed nature. An outbreak of premalignant and malignant skin lesions was reported among paraquat manufacturers in 1985. The skin lesions were mainly distributed over the sun-exposed areas. Photodamage and photocarcinogenesis revealed a strong association with exposure to bipyridines among paraquat manufacturers. In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs). Over 60% of patients were in grades O-II by the Japanese classification. The blood PCB levels of the Taiwanese patients were found to be higher than those of the Yusho subjects. PMID- 11770721 TI - Unusual urticarias. AB - Typical urticarial lesions are transient cutaneous swellings of sudden onset, often itchy, persisting for less than 24 hours and resolving to leave normal appearing skin. Angioedema lesions are similar subcutaneous lesions. Atypical urticarias persist for longer than 24 hours, may be painful and bruised in appearance and accompanied with severe systemic symptoms. Conditions where prolonged weals are present include delayed pressure urticaria and urticarial vasculitis. These conditions do not respond well to antihistamine therapy. In delayed pressure urticaria, weals appear after a delay of hours at sites of sustained pressure on the skin and occur in association with ordinary chronic 'idiopathic' urticaria. Weals of urticarial vasculitis show histological features of venulitis, and can be accompanied by arthralgia and abdominal pain. Rarely, the condition is due to infective or autoimmune disease. Urticarial diseases, sometimes with features of urticarial vasculitis, and with associated systemic features include Schnitzler's Syndrome, Still's disease and Muckle-Wells syndrome. The latter syndrome is linked with chromosome 1q44, as is autosomal dominant cold urticaria, an unusual physical urticaria. Persistent cholinergic erythema, a variant of cholinergic urticaria, has been mistaken for a drug eruption or cutaneous mastocytosis. Rarely, food and exercise induced urticaria and anaphylaxis occur when exercise follows a specific food or any meal within a few hours. The early stages of inflammatory disease may be mistaken for urticaria and angioedema, but lesions usually persist for longer than 48 hours and are accompanied by epidermal changes. PMID- 11770722 TI - Dermatoses of pregnancy: new developments. PMID- 11770723 TI - Epidermolysis bullosa: scientific advances and therapeutic challenges. AB - Epidermolvsis bullosa (EB) is a heterogeneous group of inherited skin fragility and blistering disorders. Over the last 25 years research in EB has progressed from descriptive morphological studies through quantitative ultrastructural and biochemical analysis to molecular genetic approaches, including linkage analysis, gene cloning and sequencing, and mutation screening. Currently, 10 distinct causative genes are known to underlie different forms of EB, and this knowledge has been translated to improving the clinical management of patients with these disorders. For example, first trimester DNA-based prenatal diagnosis is now available in a number of centres in different countries, including Japan, the USA and the UK, and preimplantation genetic diagnosis is also possible. The development of novel forms of treatment for enhancing wound healing and reducing blistering are the subject of an international research effort. Programmes aimed at developing gene therapy for the major forms of EB have already reached the preclinical testing stages. Despite these impressive scientific advances, EB continues to be a devastating disease, in which the high incidence of aggressive squamous cell carcinoma has a major influence on both morbidity and life expectancy, especially in patients with the severe mutilating form of dystrophic EB. PMID- 11770724 TI - 100 years of Japanese dermatology: a perspective from abroad. AB - The development of Japanese dermatology is reviewed from the times of the founding fathers and Keizo Dohi to today. Tribute is paid to the heroes of the first hour. Thereafter, an evaluation of Japanese-authored papers in the leading journal of the field (JID) over four decades is presented, taking a triennial slot in each. The contribution of Japanese- authored papers has increased substantially over this period. PMID- 11770725 TI - Pathophysiology and therapy of pemphigus in the 21st century. PMID- 11770726 TI - Bullous pemphigoid: end of the century overview. AB - Bullous pemphigoid (BP) was first described by Lever in 1953 as a subepidermal blistering disease. Immunohistological features of BP include dermal-epidermal junction separation with an inflammatory cell infiltrate in the upper dermis, and autoantibodies in patients' circulation and bound to the basement membrane zone (BMZ). These autoantibodies show a linear staining at the dermal-epidermal junction (DEJ) and recognize two major hemidesmosomal proteins, the BP230 (BPAG1) and BP180 (BPAG2). An IgG passive transfer mouse model of BP was developed, that recapitulates the key features of human BP. Using this in vivo model system, key cellular and molecular events leading to BP disease phenotype are identified, including IgG binding to its target, complement activation, mast cell degranulation, neutrophil infiltration and activation. Proteinases and reactive oxygen species released by neutrophils work together to damage BMZ, causing DEJ separation. T cells from BP patients show a specific proliferative response to recombinant BP180 NC16A. These NC16A-responding T lymphocytes express alpha/beta T cell receptors and CD4 memory T cell surface markers and exhibited a Th1/Th2 mixed cytokine profile. After almost a half-century of studies, we have learned a great deal about IgG-mediated tissue injury and begin to understand the autoimmune responses leading to pathogenic IgG production in BP. PMID- 11770727 TI - Clinical spectrum, pathogenesis and treatment of linear IgA bullous dermatosis. PMID- 11770728 TI - Recent advances in the treatment of autoimmune bullous diseases. PMID- 11770729 TI - Recent advances in dendritic cell vaccines for cancer treatment. AB - Dendritic cells (DC) are special subsets of antigen presenting cells characterized by their unique abilities to efficiently take up, process, and present various forms of antigens to immunologically naive T cells. Recent advances in the understanding of molecular mechanisms regulating the functions of DC have allowed the investigators to "design" innovative DC-based vaccine formats for the treatment of cancer patients. In this article, we will review the most advanced DC vaccine strategies, focusing on three major areas: a) new ex vivo protocols for DC loading with tumor-associated antigens (TAA), b) genetic approaches to load skin-resident Langerhans cells (LC) with TAA, and c) chemokine mediated LC entrapment and in situ loading of LC with TAA at the entrapment sites. We believe that these new classes of DC vaccine strategies will soon become applicable to the treatment of patients with malignant tumors. PMID- 11770730 TI - Imported skin diseases in dermatology. AB - Millions of afflicted people suffer from conditions which Japanese dermatologists may rarely encounter. Many of our patients travel extensively either as part of work-related business trips or during vacationing. From three to ten percent of travelers experience skin, hair or nail disorders. With worldwide travel heightening exposure to the causative agents, there is an increasing likelihood that a patient with leishmaniasis, Boutonneuse fever, onchocerciasis, loaiasis, dengue fever, cutaneous larva migrans or other recently acquired skin conditions from a far away land will visit your office for diagnosis and treatment. The clinical characteristics, diagnostic tests and therapeutic options for such imported tropical diseases will be discussed. PMID- 11770731 TI - Penicilliosis in AIDS. PMID- 11770732 TI - History of German medicine and its influence on the spirit of Japanese dermatology. PMID- 11770733 TI - Fundamental new results in the energetics and thermodynamics of charged metal surfaces. AB - There should be close scientific relationships between the following: the bonding energy of an atom or molecule at a curved surface; the Laplace-Young equation (the 'equation for pressure difference across a curved surface'); the Kelvin equation (the 'equation for vapour pressure above a curved surface'); and the thermodynamics of surface diffusion. This paper briefly reports some surprising new theoretical results obtained by reviewing these relationships, and inserting 'atomic-type' surface electrostatic energy terms into the expression for system potential energy. The two main results are as follows. First, the field dependence of atomic bonding energy is shown to be associated with a change in the electrical capacitance between the specimen and its surroundings, when the atom is removed. Good agreement is found between old experiments and the new theory. Second, when atomic-type effects are taken into account, new terms appear in the formula for pressure difference across a charged curved surface. These describe a field-dependent correction to the 'surface tension' term and a curvature-dependent correction to the Maxwell field stress term. The main consequences are: the concepts of 'surface tension' and 'surface free energy' become no longer equivalent; a small correction is needed to the Raleigh criterion for the stability of charged droplets; and a mathematical Taylor cone is no longer a hydrodynamic equilibrium shape. PMID- 11770734 TI - Characterization of a high voltage flat panel display unit using nanotube-based emitters. AB - Details are given of an experimental investigation carried out to study the field electron emission characteristics of a field emission flat panel display unit using a carbon nanotube-epoxy composite as electron emission material. These include: (i) dependence of direct emission current-voltage characteristic on vacuum gap spacing, (ii) the variation of the proportion of emission current passing through an aperture hole of a gate electrode with changing structural parameters of the device, and (iii) the uniformity and display characteristics of a typical display unit. Our findings indicate that it is very likely for one to produce a near-market prototype high voltage field emission flat panel display, if more sophisticated fabrication and assembly technique is adapted. PMID- 11770735 TI - Microfabrication and characterization of gated amorphous diamond-based field emission electron sources. AB - Gated field emission electron sources of amorphous diamond (a-D) coated Si tips and a-D diodes on a rough Si substrate were studied, detailing the deposition and characterization of the thin film, the fabrication processes and the emission behavior of the electron sources. Mechanisms responsible for the emission process of the a-D coated devices are proposed. A comparison of the field emission performance of the two types of devices is presented. In addition, future improvements of the a-D diode on a rough Si cathode are discussed. PMID- 11770736 TI - Study of field electron emission spectral characteristics of amorphous carbon nitride film. AB - The study of field electron energy spectra from amorphous carbon-nitride (a-CN) films is essential to understand the mechanism of field emission from this promising material. In this work, the electron energy spectrum is studied by measuring the distribution of electron field emitted from individual emitting sites. The spectra are recorded at different electrical fields. It is found that the peak shift as well as the half-width increase with increasing applied fields. Furthermore, multi-peak features are observed at the low-energy side of the spectra. It is assumed that these peaks might originate from the interband states of a-CN film. We propose that although the emission mainly originates from current injection into conduction band of a-CN film, the electrons may also be emitted from interband states. PMID- 11770737 TI - Study of the frequency response of the thin film cold cathode electron source of a lighting element. AB - Details of the recent experimental and theoretical studies of the frequency characteristic of the field emission electron source of a lighting element are given. The response times at different frequencies (0.02-200 kHz) and applied gap fields, acting on cathode surface, have been studied. A correlation has been found to exist between the response time and the frequency of applied voltage pulse. The response time remains almost constant within a range of frequencies between 1 and 30 kHz, and it remains nearly constant with increasing applied gap field higher than the threshold field. Finally, the cutoff frequency of the electron source is found, and with the current design of the electron source, it can be as high as 40 kHz. An equivalent circuit model is proposed, and theoretical results based on this model agree well with experimental findings. PMID- 11770738 TI - Prototypes using metal, carbon fiber and composite field emission sources modulated by a laser beam. AB - Field emission of electrons from a variety of metallic, carbon fiber and composite metal-insulator micropoint cathodes was employed in this study. Tungsten, carbon fiber and ZrC tips, were studied using a field emission microscope. These cathodes were characterized and the current-voltage (I-V) characteristics were determined. A variety of surface treatment procedures were carried out to increase the stability of emission. These electron sources were mounted in sealed prototype field emission tubes, while others were tested under medium, high and UHV conditions. The emission current switch-on phenomenon was found with all non-metallic cathodes. The emitters were then subjected to a square wave-modulated, maximally focused laser diode beam (lambda = 658 nm, 30mW). The beam impedance (approximately 1 Gohms) and the anode capacitance (approximately 10 pF) act as a low-pass filter. PMID- 11770739 TI - A new approach to the interpretation of atom probe field-ion microscopy images. AB - The field distribution and the ion trajectories close to the tip surface are known to mainly control the contrast of field-ion microscopy and the resolution of the three-dimensional atom probe. The proper interpretation of images provided by these techniques requires the electric field and the ion trajectories to be determined accurately. A model has been developed in order to compute the ion trajectories close to a curved emitting surface modelled at the atomic scale. In this model, both the gradual change of the tip surface and the chemical nature of atoms were taken into account. Predictions and results given by this approach are shown to be in excellent agreement with experiments. The calculated electric field at the tip surface is consistent with field-ion microscopy contrasts. The preferential retention of surface atoms and the order of evaporation were correctly simulated. The ion trajectories were successfully described. In this way, the crucial problem of trajectory overlap and local magnification could be investigated. These simulations not only lead to a new understanding of the physical basis of image formation, but also have a predictive value. PMID- 11770740 TI - A model accounting for spatial overlaps in 3D atom-probe microscopy. AB - The spatial resolution of three-dimensional atom probe is known to be mainly controlled by the aberrations of ion trajectories near the specimen surface. An analytical model accounting for the spatial overlaps that occur near phase interfaces is described. This model makes it possible to correct the apparent composition of small spherical precipitates in order to determine the true composition. The prediction of the overlap rate as a function of the particle size was found in remarkably good agreement with the simulations of ion trajectories that were made. The thickness of the mixed zone around beta precipitates was found to be of 0.3 nm for a normalised evaporation field of beta phase of 0.8. Using simulations, the overlap rate could be parameterised as a function of the apparent atomic density observed in particles. This model has been applied to copper precipitation in FeCu. PMID- 11770741 TI - Numerical modelling of mass resolution in a scanning atom probe. AB - We have recently suggested a novel method for improving mass resolution in the scanning atom probe (SAP), based on a post-deceleration scheme. A two-conductor counter electrode is used, and the high voltage pulse is applied to the front conductor, with the rear conductor being held at ground. For a separation between the two conductors of 100 microm or less, ions travel between the two while the pulse is essentially constant, so that the ion leaves the counter electrode with an energy equivalent to the applied d.c. potential. In this paper, we have used a numerical model for the electric fields in the SAP to verify the results of the simpler analytical approach used earlier. In particular, the ion acceleration in the vicinity of the tip, previously assumed to be instantaneous, was modelled using a hyperboloidal field approximation. The numerical model was used to calculate the flight time for ions having a range of masses and evaporating over a range of times at the peak of a high voltage pulse. Modelled mass resolutions, calculated in this way, were then compared with analytical expressions, and were found to agree very well. This shows that the earlier assumption of an instantaneous acceleration did not seriously affect the validity of the approach. PMID- 11770742 TI - Measurements of field enhancement introduced by a local electrode. AB - Direct measurements of field enhancement introduced by a local electrode have been carried out on a scanning atom probe (SAP). The results show that an enhancement factor of more than 2 can be obtained simply by reducing the specimen to-electrode distance from 1.5 mm to 10 microm. Further enhancement can be achieved if the electrode has a smaller aperture. This suggests that a specimen with tip radius of approximately 200 nm, which usually is too blunt to be analysed in a standard atom probe, could now be analysed by SAP. The capability of analysing blunt tips will expand the applicability of SAP to a much broader range of materials. PMID- 11770743 TI - Fabrication of specimens of metamorphic magnetite crystals for field ion microscopy and atom probe microanalysis. AB - Field ion specimens have been successfully fabricated from samples of metamorphic magnetite crystals (Fe3O4) extracted from a polymetamorphosed, granulite-facies marble with the use of a focused ion beam. These magnetite crystals contain nanometer-scale, disk-shaped inclusions making this magnetite particularly attractive for investigating the capabilities of atom probe field ion microscopy (APFIM) for geological materials. Field ion microscope images of these magnetite crystals were obtained in which the observed size and morphology of the precipitates agree with previous results. Samples were analyzed in the energy compensated optical position-sensitive atom probe. Mass spectra were obtained in which peaks for singly ionized 16O, 56Fe and 56FeO and doubly ionized 54Fe, 56Fe and 57Fe peaks were fully resolved. Manganese and aluminum were observed in a limited analysis of a precipitate in an energy compensated position sensitive atom probe. PMID- 11770744 TI - New results in the theory of Fowler-Nordheim plots and the modelling of hemi ellipsoidal emitters. AB - This paper reports further progress in understanding the theory of emission-area extraction from Fowler-Nordheim plots, and reports some useful interim results derived by modelling field electron emission from hemi-ellipsoidal emitters. The mathematical nature of the relationship between a new approach to emission-area extraction, recently proposed, and older approaches is demonstrated. The new approach is extended to cover field dependence in emission area. Preliminary results are reported from an investigation into the effects of making erroneous assumptions about the tunnelling barrier seen by the electron and the absence of field dependence in emission area. If wrong theoretical assumptions are made, then emission area can be overpredicted by a factor of as much as 10 or 20. On the other hand, if correct theoretical assumptions are made, then the extracted emission area is close to an emission area derived directly from the model calculations. The problematical nature of the concept of emission area, when emission area is a function of field, is pointed out. PMID- 11770745 TI - Analysis conditions of an industrial Al-Mg-Si alloy by conventional and 3D atom probes. AB - Industrial 6016 Al-Mg-Si(Cu) alloys are presently regarded as attractive candidates for heat treatable sheet materials. Their mechanical properties can be adjusted for a given application by age hardening of the alloys. The resulting microstructural evolution takes place at the nanometer scale, making the atom probe a well suited instrument to study it. Accuracy of atom probe analysis of these aluminium alloys is a key point for the understanding of the fine scale microstructural evolution. It is known to be strongly dependent on the analysis conditions (such as specimen temperature and pulse fraction) which have been widely studied for ID atom probes. The development of the 3D instruments, as well as the increase of the evaporation pulse repetition rate have led to different analysis conditions, in particular evaporation and detection rates. The influence of various experimental parameters on the accuracy of atom probe data, in particular with regard to hydride formation sensitivity, has been reinvestigated. It is shown that hydrogen contamination is strongly dependent on the electric field at the specimen surface, and that high evaporation rates are beneficial. Conversely, detection rate must be limited to smaller than 0.02 atoms/pulse in order to prevent drastic pile-up effect. PMID- 11770746 TI - Characterization of nanoscaled heterogeneities in mechanically alloyed and compacted CuFe. AB - Cu80Fe20 and Cu50Fe50 were mechanically alloyed from the pure elements by ball milling for 36 h. The alloy powder was compacted into tablets at room temperature by applying a pressure of 5 GPa. Characterization of the Cu80Fe20) and Cu50Fe50 alloys was carried out by high-resolution transmission electron microscopy (HREM), atom probe field ion microscopy and three-dimensional atom probe (3DAP). The grain size of the nanocrystalline microstructure of the ball-milled alloys observed with HREM varies between 3 and 50 nm. Atom probe and 3DAP measurements indicate that the as-prepared state is a highly supersaturated alloy, in which the individual nanocrystals have largely varying composition. Fe concentration in Cu was found to range from about 8 to 50 at%. It is concluded that by ball milling and compacting an alloy is produced which on a nanometer scale is heterogeneous with respect to morphology and composition. PMID- 11770747 TI - Nanometer-scale solute segregation at heterophase interfaces and microstructural evolution of molybdenum nitride precipitates. AB - The interrelationship between coherency and solute segregation at metal/metal nitride heterophase interfaces is studied on a subnanometer scale by both atom probe field-ion and electron microscopies for molybdenum nitride precipitates in Fe-2 at% Mo-X, where X = 0.4 at% Sb or 0.5 at% Sn. Internal nitridation at 550 degrees C generates thin platelet-shaped molybdenum nitride precipitates, while nitridation at 600 degrees C produces, in addition to the small-scale structure with precipitates of the thin-platelet type, a much coarser structure of thick plates and spheroidal precipitates. The solute species Sn and Sb segregate at the heterophase interfaces of the coarse precipitates and Gibbsian interfacial excesses of up to 7 x 10(18) M(-2) are measured. The segregation is related to the presence of misfit dislocations at the interfaces of the coarse preciptitates, while the thin plates remain coherent with no detectable segregation. PMID- 11770748 TI - Subnanometer three-dimensional atom-probe investigation of segregation at MgO/Cu ceramic/metal heterophase interfaces. AB - Three-dimensional atom-probe (3DAP) microscopy has been applied to the study of segregation at ceramic/metal (C/M) interfaces. In this article, results on the MgO/Cu(X) (where X = Ag or Sb) systems are summarized. Nanometer-size MgO precipitates with atomically clean and atomically sharp interfaces were prepared in these systems by internal oxidation. Segregation of the ternary component (Ag or Sb) at the MgO/Cu heterophase interface was enhanced by extended low temperature anneals. Magnesia precipitates in the 3DAP reconstructions were delineated as isoconcentration surfaces, and segregation of each ternary component at the C/M interfaces was analyzed with the proximity histogram method developed at Northwestern University. This method allows the direct extraction of the Gibbsian interfacial excess of solute at the C/M interfaces from the experimental data. A value of (3.2+/-2.0) x 10(17)m(-2) at 500 degrees C is obtained for the segregation of Ag at a MgO/Cu(Ag) interface, while a value of (2.9+/-0.9) x 10(18) m(-2) at 500 degrees C is obtained for the segregation of Sb at a MgO/Cu(Sb) interface. The larger Gibbsian excess for Sb segregation at this ceramic/metal heterophase interface is most likely due to the so-called pdeltaV effect. PMID- 11770749 TI - Simulations of photon-assisted tunneling using the Fokker-Planck equation to model the scattering of electrons within the emitting metal tip. AB - A method to simulate photon-assisted tunneling is developed, and applied to model laser-assisted field emission from metals. Our simulations show that most of the exchange of quanta between the electrons and the radiation occurs within the emitting metal tip. In typical experiments (lambda = 670 nm with tungsten metal) the depth of penetration for the radiation is four times the mean free path for electrons at the Fermi level, so it is necessary to allow for scattering. We use a Floquet expansion with the time-dependent Schrodinger equation to allow for the exchange of quanta between the electrons and the radiation field. Multiparticle effects are modeled with the density functional theory within the local density approximation for the Kohn-Sham exchange and correlation, and the Fokker-Planck formulation is used to determine the effects of scattering on the energy distribution of the electrons. PMID- 11770750 TI - Modeling the electron field emission from carbon nanotube films. AB - A theoretical framework for the electron field emission from carbon nanotubes (CNTs) is discussed. Using the tunneling theory, the influence of the detailed electron energy dispersion is proven to be of little importance for the electron field emission. By means of numerical computations in a simplified model, the influence of the environment on the local field on a CNT is discussed for an aligned CNT film. In a simple triangular model for the potential energy barrier at the tube end, a tunneling probability was obtained. A statistical model was developed for the structural and functional parameters of aligned CNT films. Practical CNT films of excellent alignment, obtained directly on a tungsten wire by plasma-enhanced chemical vapor deposition, were analyzed by this statistical model. Their distribution in the enhancement factors was thus deduced. An indirect method to get the average electrical parameters of the film using only a limited amount of experimental data was thus established. PMID- 11770751 TI - Dynamics of surface reactions studied by field emission microscopy and atom-probe mass spectrometry. AB - Recent progress in imaging surface chemical reactions and adsorbate-induced reconstruction by means of field ion microscopy is reviewed. Achievements and prospects of a local chemical analysis during imaging are also presented and discussed. Major shape transformation is reported to occur during the field-free interaction of oxygen with Rh crystal tips. Rather than hemispherical when clean they appear polyhedral after reaction at temperatures between 500 and 550 K. Kinetic non-linearities are found in both the NO and NO2 reaction with hydrogen on the surface of a pyramidal Pt crystal tip. Oscillatory reaction behavior is observed for both reactions. In the NO2-H2 case explosive ignition in [0 1 2] planes is followed by one-dimensional chemical wave propagation along the <1 0 0> zone lines. Atom-probe time-of-flight mass spectrometry demonstrates that water (field ionized as H2O+ and H3O+) is the product of the catalytic reaction. During the NO/H2 reaction, dynamic formation and motion of small islands are observed. These islands appear on the (0 0 1) pole and are interpreted as being due to adsorbed hydroxyl species. Island sizes are confined to the equivalent of 10-30 Pt atoms. PMID- 11770752 TI - Relationships among the physical parameters required to give a linear relation between slope and intercept of Fowler-Nordheim plots. AB - For field emitters with a given surface condition, but different apex radii, there exists an empirical linear relationship between the slopes and intercepts of their Fowler-Nordheim plots. This behavior is quite different from that predicted by the theory with the assumption of a smooth surface. We have already characterized the possible reasons for this discrepancy; one possibility is that the emission area rapidly increases with increase in the apex radius. The previous report (Jpn. J. Appl. Phys. Part II 32 (1993) L342), however, showed a curved relation between the slope and the intercept of Fowler-Nordheim plots. In the present article, we try to extract the relationship between the emission area and the apex radius needed in order to give a linear relationship between slope and intercept of the F-N plots. As an additional result of the present analysis, the change in work function of the field emitting surface is demonstrated. PMID- 11770753 TI - On the increase of the intensity ratio of doubly charged ions to singly charged ions for liquid gold and copper ion sources. AB - The reason for the increase of R21 which is defined by the intensity ratio of the doubly charged ions to the singly charged ions, was studied. Based on the conventional field evaporation theory, an increase in the electric field and/or the source temperature is considered to be attributable. We took the fact that R21 turned to decrease at the higher current regime into consideration and examined whether the change of R21 due to change in the field or temperature would finally meet the criterion for the decrease of R21. It was concluded that an increase of the source temperature may be a possible reason for the increase of R21. PMID- 11770754 TI - Field-induced electron emission from electrically nanostructured heterogeneous (ENH) materials. AB - This paper discusses the origins of field-induced electron emission from thin films of electrically nanostructured heterogeneous (ENH) materials. Such materials exhibit low macroscopic field (LMF) electron emission: as thin films on a conducting substrate, they emit electrons into vacuum when LMFs, typically about 1-10 V/microm, are applied. An ENH material comprises: a dielectric matrix, which may contain nanoscale inclusions of higher electrical conductivity; conducting channels that open in the dielectric between the inclusions (if present) and between them and the substrate; and an electron emitting channel that opens into vacuum. Electrically nanostructured heterogeneous materials can have a variety of different detailed structures and theories, but all can exhibit LMF emission under suitable circumstances. This paper provides an updated summary of an integrating overview recently presented to explain LMF emission. A central feature is that electrical nanostructure within the film can create internal field enhancement, thereby producing a high local field at the vacuum interface: this enables thermalised electrons to escape rapidly into vacuum by tunnelling. The question of what aspect of the system controls the emission current is a separate issue. Various features and implications of the theory are set out. PMID- 11770755 TI - In situ dynamic study of hydrogen oxidation on rhodium. AB - The reaction of hydrogen/oxygen gas mixtures with rhodium single crystals was studied using video-FIM (Field Ion Microscopy) at temperatures between 350 and 550 K and up to 2 x 10(-2) Pa total pressure. Imaging at 500 K in a hydrogen rich gas mixture (H2:O2 = 9) revealed considerable morphological changes of the (0 0 1)-oriented field emitter tip, i.e. the growth of low-index at the expense of high-index planes and strong crystal coarsening. Decreasing the hydrogen partial pressure led to chemical and structural changes of the Rh sample. Starting on the [1 1 0] planes a surface oxide formed, which spread anisotropically across the surface until it finally covered the whole visible surface area. The transformation was reversible upon increasing the hydrogen pressure back to its initial value. However, a hysteresis behavior was observed, i.e. a larger hydrogen partial pressure was found to be necessary to re-establish the initial patterns of a reactive Oad/Had layer. By varying the temperature from 400 to 500 K a phase diagram was established for the Oad/Had system. Increasing the electric field proved to shift the phase diagram towards higher H2 pressures. At 550K self sustained kinetic oscillations with a cycle time of approximately 40s could be observed. PMID- 11770756 TI - Analysis of fiber probes of scanning near-field optical microscope by field emission microscopy. AB - It is shown that field emission microscopy and related methods can be used to analyze the metal coated fiber tips, which nowadays are the most frequently used sensor for the scanning near-field optical microscopy (SNOM). Metal free and thus non field-emitting aperture for the light transmission on the tip apex can be directly seen and its parameters can be measured, which is very important for the interpretation of SNOM data. PMID- 11770757 TI - Confinement of surface state electrons on Cu and Au field emitters. AB - Field-emission images of clean Cu and Au emitters show a peculiar halo-like ring centered at the [1 1 1] pole. Typical diameter and width of the ring are approximately 10 nm and approximately 2 nm, respectively. Since we found no geometrical features around the [1 1 1] pole that gives rise to such a ring pattern, we interpreted the ring pattern as representing enhanced emission from an annular terrace that resonantly confines surface electrons. A simple analysis shows that the observed ring pattern appears at a terrace whose width nearly matches the confinement condition. PMID- 11770758 TI - Comparison between experimental and computer simulations of current-voltage (I-V) characteristics of dielectric-coated photon-stimulated field emitters. AB - For the purpose of simulating photon-stimulated field emission by taking account of three-dimensional aspects, a transfer-matrix formulation of electronic scattering was combined with a Floquet expansion of the wave function for taking account of quanta exchanges between the electrons and the external radiation. With specific techniques to preserve numerical stability, this transfer-matrix formalism is well suited to compute the transmission of the field-emitted/photon stimulated electrons between two electrodes. This theory is applied to the computation of Fowler-Nordheim curves describing the photon-stimulated field emission of a tungsten plane emitter (described by z< or =0), which supports a nanometric protrusion and a dielectric coating. The extraction bias ranges from 12 to 24V, for an inter-electrode distance of 4nm. The electromagnetic radiation has a wavelength of 0.67 microm and a power flux density ranging from 5.96 x 10(10) to 5.96 x 10(12) W/m2. The effects due to the protrusion and the dielectric coating are studied. These theoretical results are compared with the experimental data. PMID- 11770759 TI - Polybrominated diphenyl ether flame retardants in Virginia freshwater fishes (USA). AB - Polybrominated diphenyl ethers (PBDEs) were examined in fish fillets collected from two large Virginia watersheds. Emphasis was on the tetra- to hexabrominated congeners since these exhibit the greatest bioaccumulation and toxicological potentials. These congeners are dominant constituents of Penta-, a commercial PBDE product used to flame retard polyurethane foam. In 1999, North America accounted for98% of global Penta-demand. Concentrations of total tetra- to hexabrominated congeners in fillets ranged from <5 to 47,900 microg/kg (lipid basis). BDE-47, one of the two major constituents of Penta-, was detected in 89% of samples and contributed 40-70% of the total PBDEs observed. Concentrations of BDE-99, the second major constituent of the Penta- commercial mixture, were much lower in fish. While some differences in PBDE profiles between fish species were apparent, dominant congeners were consistent with those in surficial sediments from the Virginia sites and recently published data for U.S. air samples. PCB and PBDE concentrations in fish were generally associated. These factors point to exposure from nonpoint sources. Exceptions existed, likely due to inputs from local sources. The Virginia study area has historically served as a center for furniture and textile manufacturing, although polyurethane foam production here has been limited. PMID- 11770760 TI - Emission of chiral organochlorine pesticides from agricultural soils in the cornbelt region of the U.S. AB - Several organochlorine pesticides are chiral molecules manufactured as racemic mixtures. Past research has shown that selective degradation of pesticide enantiomers by microorganisms occurs resulting in nonracemic signatures in soils. In this work, volatilization of chiral pesticides from soil was investigated to determine if enantioselective breakdown in soils could be used as a source signature to track releases of chiral pesticides to the atmosphere. Air samples were taken directly above agricultural soils at several sites, and enantiomeric signatures were found to be nonracemic following patterns found in the soil. A follow up study at one site showed that for most compounds concentration decreased with increasing height above the soil, while enantiomer fractions for chiral pesticides were similar to that found in the soil, signifying the soil as a source to the air. The enantiomer fractions of ambient air samples from rural nonagricultural areas in the region were also found to be nonracemic. PMID- 11770761 TI - Historical PCDD inputs and their source implications from dated sediment cores in Queensland (Australia). AB - Recent investigations have demonstrated the presence of an unidentified source of polychlorinated dibenzo-p-dioxins (PCDDs) in the coastal zone of Queensland (Australia). The present study provides new information on the possible PCDD sources and their temporal input to this environment. Two estuarine sediment cores were collected in northern Queensland for which radiochemical chronologies were established. Core sections from different depositional ages, up to three centuries, have been analyzed for 2,3,7,8-substituted PCDDs and polychlorinated dibenzofurans (PCDFs). Variations of PCDD concentrations in the sediment cores over several centuries of depositional history were relatively small, and elevated PCDD levels were still present in sediment slices from the early 17th century. PCDD/F isomer patterns and congener profiles in sediments deposited during the last 350 years were almost identical and correlated well to the characteristic profiles observed in surface sediments and soils from the entire Queensland coastline. Profiles were dominated by higher chlorinated PCDDs, in particular octachlorodibenzodioxin (OCDD), whereas PCDF concentrations were below or near the limit of detection. These results indicate the presence of a PCDD source prior to industrialization and production of commercial organochlorine products. Further, the present study demonstrates that PCDD input patterns have been similar along an extensive but localized area over at least several centuries, contributing relatively high concentrations of PCDDs to the coastal system of Queensland. PMID- 11770762 TI - Atmospheric aerosol over Vermont: chemical composition and sources. AB - Aerosol chemical composition data for PM2.5 samples collected during the period from 1988 to 1995 at Underhill, VT, were analyzed. Sulfur and black carbon mass concentrations ranged from 0.01 to 6.5 microg m(-3) and from 0.05 to 2.2 microg m(-3), respectively, while the total fine aerosol mass concentration ranged from 0.2 to 51.1 microg m(-3). Seasonal variations with maxima during the summer and minima in winter/spring were observed for sulfur and the fine mass concentrations. No annual pattern was observed for black carbon. Seasonal variations for most of the other anthropogenic species had maxima in winter and spring and minima in the summer. A factor analysis method, positive matrix factorization (PMF), utilizing error estimates of the data to provide optimum data point scaling was used to obtain information about possible sources of the aerosol. An 11-factor solution was obtained. The six sources representing wood burning, coal and oil combustion, coal combustion emissions plus photochemical sulfate production, metal production plus municipal waste incineration, and emissions from motor vehicles were identified. Emissions from smelting of nonferrous metal ores, arsenic smelting, and soil particles and particles with high concentrations of Na were also identified by PMF. Potential source contribution function (PSCF) analysis combines the aerosol data with the air parcel backward trajectories. PSCF was applied to identify possible source areas and pathways that give rise to the observed high particulate mass concentrations from these 11 sources. The CAPITA Monte Carlo trajectory model was used to obtain 10 sets of 5-day air parcel back trajectories arriving every 2 h for the 7-yr period from 1988 to 1995. The PSCF plot for the black carbon factor shows high probabilities in the area surrounding the sampling site, indicating a strong local influence from residential wood combustion in northern New England and southwestern Quebec. Similar large potential source areas in the midwestern United States were identified for the two coal combustion factors. The midwestern United States was also identified as the source region for the Zn-Pb factor. The oil combustion factor was associated with the east coast of the United States. The results for the Pb-Mn factor suggests high probability over the nearby Montreal urban area and the areas in the midwestern United States. The windblown dust emissions from the areas to the north are significant contributors for the soil factor. Canadian Ni smelters are the main sources for the As factor, although there is some contribution from coal-fired power plants to the south and west of Underhill, VT. It is concluded that the combination of the two receptor modeling methods, PMF and PSCF, provides an effective way in identifying atmospheric aerosol sources and their likely locations. Emissions from different anthropogenic activities as well as secondary aerosol production are the main sources of aerosol measured in Vermont. Fuel combustion, local wood smoke, municipal waste incineration, and the secondary sulfate production collectively accounted for about 87% of the fine mass concentrations measured in Vermont. PMID- 11770763 TI - Comparative application of multiple receptor methods to identify aerosol sources in northern Vermont. AB - This study applies and compares results of four receptor modeling techniques to a common set of speciated fine particle measurement data collected ata remote site in northwestern Vermont between 1988 and 1995. Two multivariate mathematical models, positive matrix factorization and UNMIX, were applied to the measurement data and identified seven "common" sources that had similar compositions and similar fine mass contributions in both models. Two ensemble backward trajectory techniques, potential source contribution function and residence-time analysis, were also applied to evaluate and interpret the mathematical model results. The trajectory techniques indicate a strong regional character to the upwind locations associated with aerosol contributions from most of the sources identified independently by the mathematical models and help in the interpretation of those results. The process of model comparison provides insights on the strengths and limitations of the individual and combined source attribution techniques. Convergent results among the multiple methods provide a degree of confidence that each of the receptor methods may represent useful tools for future air quality management. Divergent or inconsistent results among the models can help identify limitations of the individual models and of the underlying aerosol and meteorological data sets. PMID- 11770764 TI - Proton binding by hydrous ferric oxide and aluminum oxide surfaces interpreted using fully optimized continuous pKa spectra. AB - A modified regularized least squares pKa spectrum approach is proposed to determine proton stability constants and concentrations for binding sites on hydrous ferric oxide (HFO) and aluminum oxide surfaces. Acid-base titration data are fit to a continuous binding site model for the system represented as a pKa spectrum. The modified parameter fitting method optimizes simultaneously for both smoothness of the pKa spectrum and goodness-of-fit, whereas other methods optimize for goodness-of-fit given a fixed smoothness factor. The modified method is tested with aluminum oxide and recovers values consistent with theoretical values. The regularized pKa spectrum method optimized for smoothness is applied to prepared samples of two types of HFO. The prepared HFO samples differ only in the total iron concentration of the parent solution. The resultant pKa distributions are compared to proton binding constants from MUSIC model results for crystalline iron oxides. The types of binding sites in the HFO sample are consistent with theoretical binding site stability constants for crystalline iron oxides. Overall, the prepared HFO samples have binding constants most consistent with values for lepidocrocite and goethite. PMID- 11770765 TI - Effect of redox conditions on MTBE biodegradation in surface water sediments. AB - Microbial degradation of methyl tert-butyl ether (MTBE) was observed in surface water-sediment microcosms under anaerobic conditions. The efficiency and products of anaerobic MTBE biodegradation were dependent on the predominant terminal electron-accepting conditions. In the presence of substantial methanogenic activity, MTBE biodegradation was nominal and involved reduction of MTBE to the toxic product, tert-butyl alcohol (TBA). In the absence of significant methanogenic activity, accumulation of [14C]TBA generally decreased, and mineralization of [U-14C]MTBE to 14CO2 generally increased as the oxidative potential of the predominant terminal electron acceptor increased in the order of SO4, Fe(III), Mn(IV) < NO3 < O2. Microbial mineralization of MTBE to CO2 under Mn(IV)-or SO4-reducing conditions has not been reported previously. The results of this study indicate that microorganisms inhabiting the sediments of streams and lakes can degrade MTBE effectively under a range of anaerobic terminal electron-accepting conditions. Thus, anaerobic bed sediment microbial processes may provide a significant environmental sink for MTBE in surface water systems throughout the United States. PMID- 11770766 TI - Sediment-water partitioning of inorganic mercury in estuaries. AB - The sediment-water partitioning and speciation of inorganic mercury have been studied under simulated estuarine conditions by monitoring the hydrophobicity and uptake of dissolved 203Hg(II) in samples from a variety of estuarine environments. A persistent increase in the distribution coefficientwith increasing salinity is inconsistent with inorganic speciation calculations, which predict an increase in the concentration of the soluble HgCl4(2-) complex (or reduction in sediment-water distribution coefficient) with increasing salinity. Partition data are, however, defined by an empirical equation relating to the salting out of nonelectrolytes via electrostriction and are characterized by salting constants between about 1.4 and 2.0 L mol(-1). Salting out of the neutral, covalent chloro-complex, HgCl2(0), is predicted but cannot account for the magnitude of salting out observed. Since Hg(II) strongly complexes with dissolved (and particulate) organic matter in natural environments, of more significance appears to be the salting out of Hg(II)-organic complexes. Operational measurements of the speciation of dissolved Hg(II) using Sep-Pak C18 columns indicate a reduction in the proportion of hydrophobic (C18-retained) dissolved Hg(II) complexes with increasing salinity, both in the presence and absence of suspended particles. Ratios of hydrophobic Hg(ll) before and after particle addition suggest a coupled salting out-sorption mechanism, with the precise nature of Hg(II) species salted out being determined bythe characteristics and concentrations of dissolved and sediment organic matter. PMID- 11770767 TI - Concerted chemical and microbial degradation of sulfophthalimides formed from sulfophthalocyanine dyes by white-rot fungi. AB - 3- and 4-sulfophthalimide (SPI) have recently been shown to be the major product formed by white-rot fungi upon decolorization of sulfophthalocyanine (SPC) textile dyes. To make use of this metabolic potential in textile wastewater treatment, the fungal breakdown products should be degradable by activated sludge. Here,the aerobic degradation of SPI was studied in die-away tests, and biodegradation intermediates and degradation products were analyzed by liquid chromatography-electrospray ionization-mass spectrometry. The degradation of SPI is initiated by a chemical hydrolysis to sulfophthalamic acid (SPAA) with half lives of 8 and 40 h at pH 6.5 for 4- and 3-SPI, respectively. Then, 4-SPAA can be mineralized by aerobic mixed cultures, while 3-SPAA remained stable throughout the experiment (35 d). Analogously, the potential intermediate in 4-SPAA degradation, the 4-sulfophthalic acid, but not its 3-isomer, can be completely mineralized aerobically by mixed cultures. In all chemical and microbialtransformations of these aromatic sulfonates the 4-sulfo-isomer is more reactive than the 3-isomer. The triade of fission of the SPC-system by white-rot fungi to SPI, chemical hydrolysis of SPI to SPAA, and microbial degradation of SPAA offers a pathway to mineralize the major part of the SPC system of textile dyes, whether in a respective effluent treatment system or in the aquatic environment. More general, these results illustrate on a molecular level how white-rot fungi and bacteria may cooperate in mineralizing structurally complex colored substances. PMID- 11770768 TI - Direct measurement of OH radicals from ozonolysis of selected alkenes: a EUPHORE simulation chamber study. AB - Reactions of ozone with alkenes can be a significant source of hydroxyl radicals in the atmosphere. In the present paper, the formation of OH radicals in the ozonolysis of selected alkenes under atmospheric conditions was directly observed. The experiments were carried out in the European photoreactor EUPHORE (Valencia, Spain). OH radicals were quantitatively detected by means of laser induced fluorescence (LIF) using a new analytical instrument, which has been constructed on the basis of an existing setup already established in field studies. The OH radicals observed resulted directly from the reaction of ozone with the corresponding alkene. There was no indication that OH radicals were produced in the system by secondary processes. The experimentally observed concentration-time profiles of OH and ozone were excellently described by chemical modeling using explicit reaction mechanisms. The following OH yields were derived: 2,3-dimethyl-2-butene: (1.00 +/- 0.25); 2-methyl-2-butene: (0.89 +/ 0.22); trans-2-butene: (0.75 +/- 0.19); alpha-pinene: (0.91 +/- 0.23). In addition, the experiments carried out were modeled using the Regional Atmospheric Chemistry Mechanism (RACM), an established condensed chemical model applied in tropospheric chemistry. For 2,3-dimethyl-2-butene, 2-methyl-2-butene, and trans-2 butene the calculated concentration-time profiles of OH and ozone are in quite good agreement with the experimental data. However, in the case of alpha-pinene, the model fails for the simulation of OH due to the high grade of mechanism condensation, which results in a poor characterization of the primary reaction products. PMID- 11770769 TI - Effect of emissions control programs on visibility in southern California. AB - A new method for the analysis and display of the effect of emissions controls on visibility is applied to conditions in southern California. An advanced mechanistic air quality model that represents airborne particles as a source oriented external mixture first is used to track emissions source contributions to the size distribution and chemical composition of airborne particles at Claremont, CA, under heavy smog conditions. The resulting description of the aerosol is used in a Mie scattering calculation to determine the magnitude and particle size dependence of light scattering and absorption in the atmosphere. The resulting light scattering and absorption coefficient values are supplied to an image processing-based visibility model that creates full color representations of the appearance of the local terrain in the presence of the specified level of air pollution based on satellite-generated landscape images. By linking these models, a direct connection is established between source emissions and resulting visual air quality. The composite modeling system then is used to studythe effectthat different emissions control strategies would have on visibility in southern California. An aggressive program of 92 specific emissions control measures that include primary particle controls plus controls on reactive gases that act as secondary aerosol precursors would more than double visual range at Claremont under the 1987 historical conditions studied. Synthetic landscape images show that the mountains to the north of Claremont that are not visible at a range of 10 km under base-case conditions would be visible if the emissions controls described above were applied. PMID- 11770770 TI - Application of strontium isotopes for tracing landfill leachate plumes in groundwater. AB - We are evaluating strontium isotopes as alternative tracers of landfill leachate in groundwater. The municipal landfill studied here is located in southeastern France. This landfill has no bottom liner, and wastes are placed directly on the ground. Based on the evaluation of chloride concentration, the plume extends a maximum of 4,600 m. Strontium isotopic composition characterizes two sources: natural groundwater (87Sr/86Sr = 0.708175) and landfill leachate contamination (87Sr/86Sr = 0.708457). The evolution of mixing ratios obtained with strontium reveals a second source of groundwater contamination: fertilizers (87Sr/ 86Sr = 0.707859). These results suggestthat isotopic signatures can be used to provide useful information on sources of groundwater contamination where conventional water quality parameters may yield ambiguous results. PMID- 11770771 TI - Measurement of 224Ra and 225Ra activities in natural waters using a radon-in-air monitor. AB - We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn 218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells. PMID- 11770772 TI - Impacts of heterogeneous organic matter on phenanthrene sorption: different soil and sediment samples. AB - Organic petrography has been proposed as a tool for characterizing the heterogeneous organic matter present in soil and sediment samples. A new simplified method is proposed as a quantitative means of interpreting observed sorption behavior for phenanthrene and different soils and sediments based on their organic petrographical characterization. This method is tested under singe solute conditions and at phenanthrene concentration of 1 microg/L. Since the opaque organic matter fraction dominates the sorption process, we propose that by quantifying this fraction one can interpret organic content normalized sorption distribution coefficient (Koc) values for a sample. While this method was developed and tested for various samples within the same aquifer, in the current study the method is validated for soil and sediment samples from different sites that cover a wide range of organic matter origin, age, and organic content. All 10 soil and sediment samples studied had log Koc values for the opaque particles between 5.6 and 6.8. This range of Koc values illustrates the heterogeneity of opaque particles between sites and geological formations and thus the need to characterize the opaque fraction of materials on a site-by-site basis. PMID- 11770773 TI - Salinity effect on mechanical dewatering of sludge with and without chemical conditioning. AB - The salinity levels of wastewater and sludge are relatively high in some coastal cities as they may use saline water for toilet flushing, and as such,the sludge dewaterability can be affected by it. The salinity effect on sludge dewaterability was therefore investigated through experimental testing of specific resistance in filtration (SRF), time to filter (TTF), and final solid content of sludge. SRF and TTF were determined using Buchner funnel tests. The final solid content was estimated by centrifuging the sludge at four levels of rotational speed. Sludge with three salinity levels (5,000, 10,000 and 20,000 ppm) were considered in this study. Coagulants such as alum, iron(II) sulfate, and organic polyelectrolytes were added to the sludgetostudythe dewaterability of such sludge with chemical conditioning. Experimental results show that doubling the salinity level of the sludge from 10,000 to 20,000 ppm shows not much change in SRF and TTF. Compared with the sludge without chemical conditioning, the addition of the coagulants to the sludge at a salinity level of 5,000 ppm drastically reduces its SRF and TTF. However, sludge with and without chemical conditioning at a salinity of 20,000 ppm has similar SRF and TTF. The final solid content of sludge increases almost linearly with salinity. Among the coagulants used in this study, the cationic polyelectrolyte is found to be better in improving sludge dewaterability, while iron(II) sulfate performs slightly better in enhancing the final solid content of the sludge. PMID- 11770774 TI - Hyperdisciplinarity and environmental studies. PMID- 11770775 TI - Engineered genes contaminate corn's birthplace. PMID- 11770776 TI - Deciphering PCB degradation. PMID- 11770777 TI - Massive PCB dredging proposed for Fox River. PMID- 11770778 TI - Congress considers major shift in farm policy. PMID- 11770779 TI - Modeling continent-wide contamination. PMID- 11770780 TI - Assessing the outlook for perchlorate remediation. PMID- 11770781 TI - The Feldenkrais Method: a dynamic approach to changing motor behavior. AB - This tutorial describes the Feldenkrais Method and points to parallels with a dynamic systems theory (DST) approach to motor behavior Feldenkrais is an educational system designed to use movement and perception to foster individualized improvement in function. Moshe Feldenkrais, its originator, believed his method enhanced people's ability to discover flexible and adaptable behavior and that behaviors are self-organized. Similarly, DST explains that a human-environment system is continually adapting to changing conditions and assembling behaviors accordingly. Despite little research, Feldenkrais is being used with people of widely ranging ages and abilities in varied settings. We propose that DSTprovides an integrated foundation for research on the Feldenkrais Method, suggest research questions, and encourage researchers to test the fundamental tenets of Feldenkrais. PMID- 11770782 TI - Fitness portfolio calibration for first- through sixth-grade children. AB - The purpose of this study was to develop and calibrate health-relatedfitness portfolios for 1st-6th grade students using the many-faceted Rasch model, and examine advantages and disadvantages of a portfolio assessment system based on Rasch calibration. Nine hundred ninety-five studentsfrom 23 schools infirst-sixth grade, who completed three-six of nine health-related fitness portfolios, participated in this study. Ten physical education teachers performed the grading across various portfolios and grade levels. Students'portfolios were rated using 23 predeveloped rubrics, and their scores linked through several common portfolios that were used across schools. The rating scores were analyzed using the many-faceted Rasch model, with four defined facets: portfolio, rubric, student, and rater The model-data fit was very good, and a consistent grade difference wasfound, that is, older students scored higher in fitness knowledge than younger ones. With Rasch calibration, measurement problems in conventional portfolio assessments can be eliminated, and a valid and reliable assessment system can be developed. In addition, several other measurement advantages are provided by Rasch calibration (e.g., related facets can be examined and controlled simultaneously). A large sample size and a more complex process, however, are required in the calibration stage of developing such a system using the Rasch model. PMID- 11770783 TI - Attention and motor performance: preferences for and advantages of an external focus. AB - This study examined individuad differences in the preference for and effectiveness of the type of attentional focus for motor learning. In two experiments, participants practicing a balance task (stabilometer) were asked to find out whether focusing on their feet (internal focus) or on two markets in front of their feet (external focus) was more effective. In Experiment 1, participants switched their attentional focus from trial to trial on Day 1 and used their preferred attentional focus on Day 2. In Experiment 2, participants were free to switch their attentional focus any time during 2 days of practice. Retention tests were performed on Day 3. Most participants chose an external focus. Also, they were more effective in retention than participants who preferred an internal focus. PMID- 11770784 TI - Examining the specificity of practice hypothesis: is learning modality specific? AB - The specificity of practice hypothesis was examined using a tracking task. In Experiment 1, visual or auditory feedback about performance was provided. Vision was more useful than audition early in acquisition. Performance gains found in acquisition were maintained during retention, but learning was specific only if the acquisition modality was visual. Specificity did not increase with the amount of practice. In Experiment 2, visual and auditory information were combined. Again, the specificity of practice hypothesis was supported. Also, instructing participants to attend to one information source allowed us to demonstrate that information can be explicitly or implicitly processed. Further, specificity effects may occur because of different rates of development for error detection and correction processes. PMID- 11770785 TI - An investigation of commitment among participants in an extended day physical activity program. AB - This study examined underserved youth participants' perceptions of commitment to an extended day physical activity program using Hellison's (1995) responsibility model. Seven participants ranging in age from 12 to 15 years participated in the study. Two personal interviews and a focus group interview were used to obtain participants' perceptions ofprogram commitment. Results revealed that program organization, personal characteristics, development of interpersonal relationships, and the program environment influenced their program commitment. Participants described the nature of commitment in terms of program behavior, emotional involvement, and program history. While the type of activity was cited as a positive influence on program commitment, the specific activity could also serve as a barrier to program commitment. Implications for program development andfuture research are offered. PMID- 11770786 TI - Description of an expert teacher's constructivist-oriented teaching: engaging students' critical thinking in learning creative dance. AB - The focus of this study was to investigate how an expert teacher implemented constructivist-oriented teaching strategies to engage students'critical thinking skills in learning creative dance. The data were collected through videotaping 16 creative dance lessons taught by an expert teacher to 2 kindergarten, 2 first grade, and 4 third-grade classes and conducting two formal interviews and several informal interviews with the teacher. In addition, one group interview was conducted with 4 kindergarten students, 4 first-grade students, and 8 third-grade students. The three salient themes were: (a) relating students' knowledge and ideas to lessons to spark dispositions, (b) encouraging and facilitating students' inquiries and creative products, and (c) engaging students' metacognition in refining the quality of dance movement. PMID- 11770787 TI - Social support and recovery from sport injury: elite skiers share their experiences. AB - Research suggests that social support can be an important coping resource for athletes recovering from sport injury. Few studies have investigated this claim, however. To address this gap in the literature, 10 elite downhill skiers who had recovered from serious sport injuries were interviewed about the sources of stress associated with injury and the role of social support in recovery from sport injury. This paper presents the social supportfindings that emergedfrom this research'. Content analyses of the social support data revealed that the skiers needed various types of emotional, informational, and tangible support from the occurrence of injury through the return to full activity. Members of the treatment team, the ski team, and the skiers' home support net works provided social support throughout these phases. In general, the skiers were satisfied with the support received, indicating that it reduced distress and kept them motivated throughout recovery. The findings from this research have implications for the design of sport injury interventions. PMID- 11770788 TI - The effects of a motivational general-mastery imagery intervention on the sport confidence of high-level badminton players. AB - A multiple-baseline across-participants design was used to examine the effects of a Motivational General-Mastery imagery intervention on the sport confidence of 4 high-leveljunior badminton players. Sport confidence data were collected once a week for 21 weeks prior to international and county matches. The imagery intervention consisted of six imagery sessions (two per week for 3 weeks) and was administered using a multiple-baseline design with interventions commencing at Weeks 5, 7, 9, and 11 for Participants 1, 2, 3, and 4, respectively. Results of visual inspection and Binomial tests suggested significant increases in sport confidence for Participants 1 and 2, a significant decrease in sport confidence for Participant 3, and a delayed increase in sport confidence for Participant 4. The results are discussed in terms of the implications of using mastery imagery and the usefulness of multiple-baseline designs for furthering imagery research. PMID- 11770789 TI - Validating motivational readiness for exercise behavior with adolescents. AB - The stages of motivational readiness as conceptualized by the Transtheoretical Model have been widely used among adult samples to assess readiness for adopting exercise behavior. To date, little research has been conducted using a staging framework with adolescent samples. There is a need for validation of the staging framework prior to a substantial amount of research with this age group. The current article presents two studies assessing stage and reported exercise behavior (Study 1: n = 819; M age = 15.0 years, SD = 1.2; 51% men; Study 2: n = 184; M age = 18.6 years, SD = .5; 45% men). As hypothesized in both studies, reported exercise consistently varied as a function of stage classification; those in earlier stages of readiness reported less exercise than those in later stages. Staging algorithms showed good sensitivity to detect reported exercise; however, specificity was distinctly better with the algorithm that used a specific activity criterion and immediate intention, as opposed to irregular behavior, in defining the preparation stage. Results support the validity of the staging framework for measuring motivational readiness for exercise behavior among North American adolescents. PMID- 11770790 TI - A 10,000-step count as a physical activity target for sedentary women. PMID- 11770791 TI - Acute ballistic muscle stretching inhibits maximal strength performance. PMID- 11770792 TI - Memory-influenced biases in gymnastic judging occur across different prior processing conditions. PMID- 11770793 TI - The treatment of anemia in peritoneal dialysis patients. AB - The management of anemia in patients with end-stage renal disease (ESRD) treated with peritoneal dialysis (PD) has gained increasing attention over the past decade, similar to patients on hemodialysis (HD). However, there are many differences between the 2 renal replacement therapies that pose unique challenges and solutions for monitoring, diagnosis and treatment of anemia in PD patients. These differences are not always evident and may be the result of different patient selection, physical, emotional and motivational factors, specific requirements of the modality or an indeterminate blend of infinite gradations of all these factors. This review will highlight current issues in anemia management in PD patients. PMID- 11770794 TI - IgM anticardiolipin antibodies are associated with stenosis of vascular access in hemodialysis patients but do not predict thrombosis. AB - AIM: The prevalence of anticardiolipin antibodies (ACA) is elevated amongst hemodialysis patients as compared with the general population. Previous studies have disagreed as to whether the presence of ACA represents a risk factor for access thrombosis. Other risk factors for access thrombosis (decreased blood flow, elevated venous pressure) have also been described. MATERIALS AND METHODS: We performed a combination retrospective and prospective cohort study of a single outpatient dialysis unit to assess the association between these potential risk factors and access thrombosis. ACA, access blood flow, presence of stenosis, and venous pressures were measured in 100 patients. Information on episodes of access thrombosis was gathered for 12 months prior to and 12 months after ACA measurement. RESULTS: ACA were present in 19% of patients with equal numbers of IgG- and IgM-ACA. The presence of IgM-ACA was significantly associated with the use of aspirin and the presence of stenosis by Doppler at the time of ACA testing (p < 0.05). A logistic regression model was used to estimate the association between clinical factors and access thrombosis. In this multivariate analysis, the presence of access stenosis and a history of access thrombosis were both significantly associated with the development of access thrombosis. Adjusted for these variables, neither IgG- nor IgM-ACA was significantly associated with access thrombosis. The presence of an ACA was not associated with episodes of access thrombosis in either the prospective or retrospective analyses. CONCLUSION: Further investigation is required to determine if the association between aspirin use and IgM-ACA, or of IgM-ACA and access stenosis, has implications for underlying pathogenetic mechanisms of access stenosis. PMID- 11770795 TI - Determinants of arterial compliance in patients treated by hemodialysis. AB - BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality among hemodialysis patients. Several studies have demonstrated the importance of a reduction in arterial compliance in the development of cardiovascular complications, reflecting the interaction of functional and structural alterations of the peripheral arterial system and left ventricle. The aim of the present study was to demonstrate that arterial compliance, evaluated by automated recording of the QKd interval, was lower in hemodialysis patients than in normal subjects. A secondary objective of the study was to assess the influence of several factors, including calcium-phosphorus parameters, on decreased arterial compliance in these patients. PATIENTS AND METHODS: Arterial compliance was evaluated in 24 chronic hemodialysis patients who had normal (n = 12) or high blood pressure (n = 12), using a method of measuring systolic wave velocity by automated recording of the QKd interval. This interval corresponds to the time (in ms) between the onset of the electrocardiogram QRS complex (Q) and the Korotkoff (K) sound at diastolic pressure (d) heard over the brachial artery during blood pressure measurement. The analysis was performed in comparison with reference values obtained in a population with normal renal function. The other parameters determined were: age, duration of chronic renal failure, duration of hemodialysis therapy, left ventricular mass, vascular calcification score, serum total and ionized calcium, phosphorus, parathyroid hormone, calcidiol, calcitriol, and blood concentration of hemoglobin. RESULTS: The arterial stiffness of all the patients was increased significantly (p < 0.001) compared to reference values obtained from subjects without renal failure, the average age, height, and blood pressure of whom were similar to those of the patients. Multivariate analysis demonstrated a positive relationship among the QKd interval, serum total calcium, and the duration of hemodialysis. This suggested that arterial wall elastic properties were dependent not only on hypertension and constraints of pressure, but that they were also influenced by calcium and phosphorus metabolism and the duration of renal substitution therapy. CONCLUSIONS: Arterial compliance, evaluated by the ambulatory method of QKd measurement, is reduced in chronic hemodialysis patients, and is inversely correlated with serum calcium concentration and dependent on the previous duration of hemodialysis therapy. PMID- 11770796 TI - Zinc nutritional status modifies renal osteodystrophy in uremic rats. AB - BACKGROUND: Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. METHODS: Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. RESULTS: After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25 hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. CONCLUSIONS: Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease. PMID- 11770797 TI - Tubular osteopontin expression in patients with ANCA-associated glomerulonephritis. AB - OBJECTIVE: To elucidate the role of osteopontin (OPN) in monocyte recruitment in crescentic glomerulonephritis, we investigated immunohistochemical localization of OPN in the kidney and its correlation with clinical and histopathologic parameters in biopsy specimens of patients with myeloperoxidase antineutrophil cytoplasmic autoantibody- (MPO-ANCA) associated glomerulonephritis. METHODS: Twelve patients with MPO-ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters such as creatinine clearance and urinary protein excretion of each patient were obtained at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining using the LSAB method. Five cortical interstitial fields randomly selected at original magnification x 200 were assessed using a computer-assisted color image analyzer. Tubular OPN expression was assessed as the percentage of positive area in the tubulointerstitium. Double immunofluorescent staining using antibodies against OPN and alpha(v)beta3 was performed. RESULTS: In all of the cases studied, OPN was occasionally localized within the glomeruli, and expressed slightly in proximal tubular epithelium and significantly in distal tubular epithelium. Tubular OPN expression tended to be promoted in the interstitium infiltrating by numerous monocytes/macrophages. The extent of tubular OPN expression was positively correlated with serum ANCA titers and urinary OPN concentrations. Enhanced alpha(v)beta3 expression appeared in the distal tubular epithelium expressing OPN. CONCLUSION: These results suggest that inducible expression of OPN and alpha(v)beta3 in the tubular epithelium seems to be associated with interstitial moncyte infiltration and subsequent tubulointerstitial changes in human MPO-ANCA-associated glomerulonephritis. PMID- 11770798 TI - Cystinuria phenotyping by oral lysine and arginine loading. AB - BACKGROUND: Cystinuria is an inherited disorder of cystine and dibasic amino acids transport that results in urolithiasis because of poor cystine solubility. Three cystinuria phenotypes, differentiated according to urinary amino acid excretion in obligate heterozygotes, were regarded as allelic variants of a monogenic disease. Two mutated amino acid transporter genes, however, have been recently identified as responsible for cystinuria. Mutations in the SLC3A1 gene. encoding for the heavy subunit of the transporter protein rBAT, were associated with type I cystinuria, whereas type II and III cystinuria were associated with mutations in the SLC7A9 gene, encoding for a light subunit of rBAT. Lysine and arginine metabolism have, therefore, been evaluated in cystinuria homozygotes and heterozygotes to better define the cystinuria phenotypes and their correlations with these emerging genotypes. PATIENTS AND METHODS: Lysine and arginine intestinal absorption and renal excretion were assessed by oral loading and compared to normal controls. Seven cystinuria homozygotes and 7 obligate heterozygotes belonging to the different types received alternately an oral dose of 0.5 mmol/kg body weight lysine or arginine. Plasma concentrations of lysine, arginine, ornithine (derived from rapid arginine conversion) were measured 0, 1, 2, and 3 hours after loading. Their urinary concentrations were measured in morning urine and in urine collected 0-6 hours after loading. RESULTS: Gut lysine absorption was deficient in type II and III, and normal in type I cystinuria homozygotes. Impaired arginine intestinal absorption, as well as massive lysine, arginine, and ornithine hyperexcretion were shared by all homozygotes, irrespective of the type. All heterozygotes shared normal lysine absorption, whereas arginine absorption was slightly impaired in type II and III heterozygotes, which also displayed high lysine, arginine, and ornithine urinary excretion after loading. CONCLUSIONS: Two cystinuria phenotypes, type I and non type I, can be identified in both homozygous and heterozygous cystinuric subjects by oral loading tests with lysine and arginine. In agreement with recent molecular findings, non-type I cystinuria comprises mentioned type II and type III, which constitute allelic variants of a cystine and dibasic amino acid transport disorder distinct from type I cystinuria. PMID- 11770799 TI - Association of the DD genotype and development of Japanese type 2 diabetic nephropathy. AB - We determined the insertion/deletion (I/D) polymorphism of the angiotensin coverting enzyme (ACE) gene in a multicenter trial of ethnically homogeneous Japanese type 2 diabetes mellitus (DM) patients. All patients (n = 748) were divided into 5 groups as follows: group I (normoalbuminuric patients), group II (microalbuminuric patients), group III (overt albuminuric patients with serum creatinine (s-Cr) levels of less than 1.2 mg/dl), group IV (overt albuminuric patients with s-Cr levels of more than 1.3 mg/dl but excluding hemodialysis patients), and group V (hemodialysis patients). We selected patients with a diabetic duration of more than 15 years in the mild stage (groups I and II), but placed no limits on those in the advanced and end-stages (groups III, IV and V). The frequency of the DD genotype was slightly higher in the advanced and end stages. The frequency of the DD genotype in the mild stage differed from that in the end stage (II/ID/DD 47.8%/41.0%/11.2% vs. 37.0 %/43.3%/19.7% p = 0.07, II + ID/DD 88.8%/11.2% vs. 80.3%/19.7%, p < 0.05). D allele frequency in the mild stage also differed from that in the end stage (I/D 68.3%/31.7% vs. 58.7%/41.3%, p < 0.02). The presence of the DD genotype increased the risk of end-stage renal disease (ESRD) more than that of the other genotypes (odds ratio ID/II = 1.37, 95% CI 0.82-2.27; DD/II = 2.27, 95% CI 1.12-4.61). It appears that the DD genotype is associated with progression of Japanese type 2 diabetic nephropathy. PMID- 11770800 TI - Necrotizing fasciitis in a renal transplant recipient treated with FK 506: the first reported case. AB - Necrotizing fasciitis is a rare but devastating condition usually caused by group A streptococci. A renal transplant recipient with necrotizing fasciitis complicated by the streptococcal toxic shock syndrome is presented. The importance of prompt diagnosis, antimicrobial treatment and early surgical intervention in achieving a successful outcome is discussed. PMID- 11770801 TI - Reply to Taskapan. PMID- 11770802 TI - Severe glomerulonephritis and isolated ileitis in adult Henoch-Schoenlein purpura. PMID- 11770803 TI - Reply to Leens. PMID- 11770804 TI - RPA white paper on commercial payers. Renal Physicians Association. PMID- 11770805 TI - Head circumference in chronic renal failure from birth. AB - AIMS: Chronic renal failure in childhood jeopardizes both growth and development. In children with chronic renal failure from birth, growth in height and weight have been found to be generally poor. Few data on head circumference are available. MATERIAL: A cohort of 19 children with chronic renal failure from birth was studied from the early weeks of life to the age of 5 years. There were 18 boys; and 18 patients had congenital renal hypoplasia or hypodysplasia associated with obstructive uropathies. Eight patients received recombinant growth hormone (rhGH) after the age of 2 years. Only 2 patients needed renal replacement therapy before the age of 5 years. Data after transplantation were not included. METHODS: The following variables were analyzed: body height, body mass index and head circumference. Data were expressed in median values of standard deviations scores (SDS). RESULTS: In the first 3 months of life there was a significant drop in height SDS, body mass index SDS and head circumference SDS. Thereafter, a stable growth velocity was observed for the rest of the study period, except for body mass index SDS. which improved after 36 months. There was a striking difference between patients who needed treatment or not with recombinant human growth hormone (rhGH). Patients without rhGH displayed a stable growth after the age of 3 months until 5 years of age. In the remaining 8 patients, rhGH treatment resulted in a significant increase not only in height SDS but also in head circumference SDS. CONCLUSIONS: In infants and young children with chronic renal failure from birth, growth in head circumference parallels growth in body height. This applies to all patients and to data before and during rhGH treatment. PMID- 11770806 TI - Normal statural growth in 2 infants on chronic peritoneal dialysis: anecdotal or whole management-related. AB - AIMS: Growth retardation is usual in children on chronic peritoneal dialysis (CPD). Despite attention to many contributing factors (nutrition, dialysis dose, hemoglobin level, adynamic bone disease, hyperparathyroidism or rickets, growth hormone resistance, etc.), normal growth is rarely obtained in infants on CPD. MATERIALS AND METHODS: We had the chance to observe normal growth over a 1 year period in 2 consecutively treated infants on CPD. Louise (renal hypodysplasia) required CPD at the age of 1 month: creatinine 430 micromol/l; oliguric, creatinine clearance lower than 5 ml/min/1.73 m2. Nutrition was achieved orally with human milk during the first 6 months of life. Tidal peritoneal dialysis allowed a high dialysis dose Kt/V urea 3.8/week and Kcreatinine 105 l/week/1.73 m2. Hemoglobin was maintained over 13 g/dl and low levels of vitamin D analogue were prescribed to avoid adynamic bone disease. At the age of 1 year her height was 75 cm. i.e. in the normal range for age. Madeline (renal hypodysplasia) commenced on CPD at the age of 6 weeks and managed similarly. Her height at 1 year of age was 74 cm. RESULTS: In our 20 years of experience with children on dialysis, these 2 cases of normal statural growth for age at 1 year warrant discussion. As well as nutritional support, the new and recent therapeutic options in our team were: firstly, to avoid high doses of activated vitamin D to control PTH, as high doses are able to induce both a risk of adynamic bone disease and a direct bone cartilage toxicity: secondly, to maintain normal hemoglobin level; and thirdly, to deliver a high dialysis dose (urea, creatinine clearance) based on an individually adapted prescription. CONCLUSION: We feel this management approach is necessary to achieve optimal statural growth in children on chronic peritoneal dialysis. But this management concept only based on clinical anecdotal observations needs further evaluation before its use in clinical guidelines. PMID- 11770807 TI - Enhanced plasma levels of advanced glycation end products (AGE) and pro inflammatory cytokines in children/adolescents with chronic renal insufficiency and after renal replacement therapy by dialysis and transplantation--are they inter-related? AB - AIMS: Advanced glycation end products (AGEs) are formed by non-enzymatic glycation or glycoxidation. After their interaction with specific receptors, they may induce expression of various proinflammatory cytokines. AGEs were shown to accumulate with advanced age, in diabetes mellitus and, in particular, in patients with chronic renal failure. In contrast to numerous investigations in adults, there are no data on plasma levels of AGEs in children with chronic renal insufficiency (CRI) and after renal replacement therapy. To elucidate the specific role of renal impairment for the formation of AGEs, these data become especially interesting by exclusion of the age-dependent modulatory effects occurring in adults. Therefore, we investigated the concentrations of fluorescent (FL) AGEs, carboxymethyllysine (CML) and markers of inflammation (CRP, IL-6, TNF alpha) in children/adolescents with chronic renal insufficiency (CRI) and on renal replacement therapy with maintenance dialysis (D) or renal transplantation (TX). PATIENTS: Eleven CRI patients on conservative treatment (CRI, age: mean 12.6, median 12.80, SD 5.8 +/- 1.7 years, serum creatinine: 205.7, 157.5, 58.0 micromol/l, respectively), 10 patients on D (13.6, 13.0, 5.4 years, and 698.2, 633.8, 296.1 micromol/l, respectively) and 9 patients after TX (15.9, 16.0, 3.4 years, and 115.9, 128.0, 35.1 micromol/l, respectively) were included. METHODS: Plasma levels of CML, TNF-alpha, and IL-6 were determined by ELISA, FL-AGEs spectrofluorimetrically (lambda(ex)/lambda(em): 370/440 nm). RESULTS: FL-AGEs and CML levels were increased in all 3 groups with the highest levels in the D patients, a successful renal transplantation did not lead to normalization of plasma AGEs. The mean CRP and IL-6 concentrations were marginally elevated, and no significance among groups was revealed. TNF-alpha was noticeably elevated in all groups, with the highest values in CRI and TX patients, while in the dialysis patients the rise was less pronounced. Stepwise multiple regression did not reveal any correlation between AGEs and proinflammatory parameters, even after exclusion of the TX group from analysis. CONCLUSIONS: In children with CRI and on maintenance dialysis therapy, plasma AGE levels are markedly increased. After renal transplantation, AGE levels decrease without normalization. Proinflammatory parameters (except for TNF-alpha) are only mildly to moderately elevated. No association between AGE levels and data characterizing a proinflammatory state was revealed. PMID- 11770808 TI - Cyclosporine nephrotoxicity: associated allograft dysfunction at low trough concentration. AB - A case report on the nephrotoxic effect of cyclosporine in a 9-year-old boy with a kidney transplant is presented. Nephrotoxicity was present even at low trough cyclosporine concentration. The literature on the range of cyclosporine nephrotoxicity is reviewed. Cyclosporine (CsA), a fungal decapeptide first introduced in 1983, has significantly improved the outcome of renal transplantation, and remains the first line immunosupressant for pediatric recipients. CsA has a narrow therapeutic range because of the fine line between adequate immunosuppression and the risk of drug-induced side effects. Furthermore, considerable inter- and intrapatient variability does exist [Filler et al. 1999]. The pre-dose trough concentration is routinely used for therapeutic drug monitoring [Bunchman et al. 1998]. The most significant side effect is nephrotoxicity, which may present differently at different times after transplantation. Renal vasoconstriction, especially involving the afferent renal arterioles, has been strongly implicated as a primary factor in acute reversible CsA nephrotoxicity. Alpha-adrenergic and calcium channel blockade with either verapamil or nifedipine ameliorates vasospasm and impairment of renal function that accompany CsA toxicity. Because of this vasoconstrictive effect, CsA may increase ischemic graft damage in the early posttransplant period. CsA side effects can be eliminated by reducing the dosage of the drug. We present an unusual case of nephrotoxicity and impaired renal function with a very low CsA blood trough concentration (50 ng/ml) on posttransplant treatment. The side effects subsided only after the discontinuation of CsA. PMID- 11770809 TI - Central nervous system involvement in hemolytic uremic syndrome (HUS)--a retrospective analysis of cerebral CT and MRI studies. AB - PURPOSE: To evaluate the morphological changes of cerebral involvement in children with HUS utilizing CT and MRI. METHOD AND PATIENTS: We retrospectively analyzed 13 cranial CTs (CCT) and 3 cranial MRI studies of 5 out of 93 patients with clinically proven HUS and severe CNS involvement (seizures and coma and dysregulation of breathing) referred to the department of pediatric nephrology (aged 1.5-15 years, median 2 years, 2 girls, 3 boys) between 1987-2000. RESULTS: Three of 5 patients had CT and MRI studies, 2 patients had CT scans only. One of 2 patients with isolated basal ganglia ischemia and normal first CCT developed a secondary hemorrhagic infarction. Another patient with an initially normal MRI developed an infarction of the right cerebral arteries with mass effects. One of 2 patients with basal ganglia involvement showed additional infarction of thalami and external and internal capsules whereas the other had only minimal involvement of adjacent white matter, but consecutive hemorrhagic infarction. Four of 5 children died (3 of them with varying extents of basal ganglia and adjacent white matter involvement, 1 with right cerebral artery infarction). Basal ganglia involvement was found in the majority of cases as well as in all lethal cases. The surviving patient with isolated basal ganglia involvement now suffers from tetraspastic disorder and convulsions. CONCLUSION: Cerebral involvement is one of the major complications of HUS. According to the literature, basal ganglia involvement in HUS is common and quite often associated with other cerebral pathologies. First imaging findings may not show pathologies. Contradictory to previous reports, even children with isolated basal ganglia pathology and/or less involvement of white matter and coma may either die from the underlying disease or their clinical outcome may be poor. PMID- 11770810 TI - Course of glomerular filtration rate after renal transplantation and the influence of hypertension. AB - INTRODUCTION: A gradual decline in the glomerular filtration rate (GFR) is a general problem in patients after renal transplantation that may be due to several factors. METHODS: The glomerular filtration rate (GFR) was estimated using the corrected Schwartz formula in 16 pediatric renal transplant recipients over a period of 5 years post-transplant. Several potential risk factors for graft outcome were analyzed. The mean age of the patients (8 female, 8 male) at the time of transplantation was 11.1 years (range: 2.7-17.3). All patients received a cadaveric renal graft for the first time. Immunosuppression consisted of cyclosporine in combination with steroids in all children treated; 3 patients received azathioprine in addition. Blood pressure (BP) was monitored regularly and its extent was expressed by an antihypertensive treatment (AHT) score. RESULTS: At the end of the first post-transplant year the mean GFR was 88 +/- 24 ml/min/1.73 m2. During the following 4 years the GFR declined to 68 +/- 29 ml/min/1.73 m2 representing an overall GFR loss of 20 ml/min/1.73 m2 (23%). With regard to the GFR loss, 2 groups could be distinguished. The first group of 7 patients showed a significant GFR decrease from 89 +/- 26 to 49 +/- 27 ml/min/1.73 m2 (p = 0.0025), whereas the second group of 9 patients had a relatively constant GFR during the 5 years (87 +/- 26 and 83 +/- 24 ml/min/1.73 m2). In each group, two acute rejections were observed in the first post transplant year. Blood pressure, expressed by an AHT score, increased in Group 1 moresso than in Group 2 during the 5 years. CONCLUSION: During the course of a 5 year period post-transplant the GFR declined significantly in 7 of 16 patients. One of the factors responsible for GFR loss is probably the increase in blood pressure. PMID- 11770811 TI - Incidence of de novo malignancies in renal transplant patients after anti-T lymphocytic therapy. PMID- 11770812 TI - Risk of steroid withdrawal in pediatric renal transplant patients with suspected steroid toxicity. AB - BACKGROUND: Glucocorticoids are still a cornerstone in immunosuppressive regimens in pediatric patients after renal transplantation (Tx). Due to the side effects, steroid withdrawal may significantly improve the appearance and growth of children with renal grafts, but bears a substantial risk for late rejections. AIM OF THE STUDY: To investigate whether exclusion of subclinical acute rejection by renal histology in combination with a prolonged steroid withdrawal period is predictive of a successful outcome. PATIENTS AND METHODS: Ten children (5 females) with a median age of 12.3 (range 7.9-20.9) years and 1.8 (0.7-7.5) years after Tx with a stable graft function and a median calculated creatinine clearance (C(Cr)) of 71 (60.5-99.7) ml/min/1.73 m2 were included. All patients showed steroid toxicity signs. Immunosuppressive regimen included low-dose steroids (median 2.72 mg/m2) in all patients, in addition to cyclosporin A (CsA) and azathioprine in 8, CsA on its own and CsA combined with mycophenolate mofetil in one patient each. A graft biopsy was performed in 8 patients prior to the start of steroid withdrawal, which was done over a median period of 6 months. Renal function was calculated as creatinine clearance using the Schwartz formula. RESULTS: None of the biopsied grafts showed histologic signs of rejection. Cyclosporin A dosage and trough levels were not significantly different before and after steroid withdrawal. While steroid side effects improved in most of the patients after withdrawal, C(Cr) decreased significantly within a median observation time of 42 (11.4-49.3) months. This decrease was due to loss of renal function in 4 patients who had biopsy-proven rejection episodes at 21.6 (8.1 29.9) months after the start of steroid withdrawal. CONCLUSION: Slow steroid withdrawal in pediatric Tx patients using conventional immunosuppression reduces side effects, but bears a high risk of late rejection. A pre-withdrawal renal biopsy was not useful for the prediction of successful steroid withdrawal. PMID- 11770813 TI - Antenatal oligohydramnios of renal origin: postnatal therapeutic and prognostic challenges. AB - Urinary tract anomalies (UTA) including polycystic kidney disease nowadays can be detected antenatally by ultrasound. The concomitant presence of oligohydramnios has been regarded as a severe risk factor for renal dysfunction and pulmonary hypoplasia, although clinical data after birth are scarce. We report the postnatal course and long-term follow-up of 10 infants with oligohydramnios due to congenital UTA from two pediatric nephrology centers. The underlying final diagnoses were autosomal-recessive polycystic kidney disease (ARPKD, n = 2), familial tubular dysgenesis (n = 2) and bilateral renal hypoplasia (n = 6) including 3 children with posterior urethral valves. Two children died in the neonatal period while 8 children are currently alive at a median age of 2.5 (range 1.1-10) years. In the postnatal period, respiratory failure necessitating mechanical ventilation occurred in 7 infants (including the 2 non-survivors). All surviving children had chronic renal failure, which could be managed conservatively in 6 children (median GFR 45 (range 15-53) ml/min/1.73 m2) while 2 reached end-stage renal disease; one undergoing preemptive kidney transplantation and one peritoneal dialysis. Seven of 8 children reached normal developmental milestones. In conclusion, the presence of antenatal oligohydramnios in infants with UTA does not always carry a poor prognosis. The high incidence of perinatal complications, the complexity of underlying causes and the prevalence of postnatal chronic renal dysfunction calls for a multidisciplinary approach in the management of these children. PMID- 11770814 TI - Understanding Trichoderma: between biotechnology and microbial ecology. PMID- 11770815 TI - Classification and mode of action of membrane-active bacteriocins produced by gram-positive bacteria. AB - Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microorganisms belonging to different eubacterial taxonomic branches. Most of them are small cationic membrane-active compounds that form pores in the target cells, disrupting membrane potentials and causing cell death. The production of small cationic peptides with antibacterial activity is a defense strategy found not only in bacteria, but also in plants and animals. Bacteriocins are classified according to different criteria by different authors; in this review, we will summarize the principal bacteriocin classifications, highlight their main physical and chemical characteristics, and describe the mechanism of some selected bacteriocins that act at the membrane level. PMID- 11770816 TI - Hydrophobicity and adhesion to fish cells and mucus of Vibrio strains isolated from infected fish. AB - The hydrophobicity of 44 Vibrio strains isolated from cultured, diseased gilt head sea bream (Sparus aurata) was determined. Three different methods were used: (1) microbial adhesion to hydrocarbons (MATH), either with phosphate buffer or with phosphate urea magnesium sulfate (PUM) buffer, (2) aggregation in the presence of salt solutions (SAT), and (3) adhesion to nitrocellulose filters (NCF). The results show that experimental conditions exerted a significant influence on hydrophobicity. Thus, Kendall rank coefficients showed the presence of correlation only for SAT and NCF, and for SAT and the MATH assay with PUM buffer. Moreover, no relationships were observed between the bacterial hydrophobicity estimated with the methods mentioned above and the ability of the strains to adhere to fish mucus or cells. These results indicate that adhesion of pathogenic Vibrio strains to host surfaces is mediated mainly by specific receptor interactions, instead of by hydrophobic interactions. PMID- 11770817 TI - Changes in the photosynthetic apparatus of diatoms in response to low and high light intensities. AB - The centric diatom Cyclotella cryptica and two strains of the pennate diatom Phaeodactylum tricornutum were grown under low and high light intensities (300 lux and 3,000 lux) over 4-6 weeks. Growth was monitored by repetitive cell count. The culture media were replaced weekly to avoid morphological and biochemical alterations caused by nutrient depletion. The ultrastructure of the cells was examined by transmission electron microscopy. Alterations in the light-harvesting antenna systems were investigated by Western immunoblotting. Both diatoms reduced the plastid area, i.e. decreased the amount of thylakoid lamellae, under high light intensity. The thylakoids still ran in groups of three with parallel orientation within the chloroplasts. The girdle band lamellae were not affected. The amounts of storage compounds and vacuoles increased. SDS-PAGE of total cell protein followed by Western immunoblotting with antisera directed against subunits of the light-harvesting antenna systems of C. cryptica (cc-antiserum) and the cryptophyte Cryptomonas maculata (cmac-antiserum) revealed that both diatoms reduced the amount of antenna polypeptides under increased light intensity. The cc-antiserum immunodecorated two bands with relative molecular masses (Mr) of 18,000 and 22,000 in C. cryptica. Both decreased under high light conditions to 67.2 +/- 6.1%. Five to seven bands in the Mr range of 14,000-27,000 were recognized in P. tricornutum. They decreased to 83 +/- 5.3%. Furthermore, the immunolabeling pattern for both strains differed under the two light regimes. The cmac-antiserum immunodecorated two polypeptides with Mr of 24,000 and 23,000 in C. cryptica, while both strains of P. tricornutum had five polypeptides in the Mr range of 14,000-24,000 that showed some differences in staining intensities between the two strains and in response to the light intensity applied. PMID- 11770818 TI - Screening of antimicrobial activities in red, green and brown macroalgae from Gran Canaria (Canary Islands, Spain). AB - Extracts from 44 species of seaweed from Gran Canaria (Canary Islands, Spain) were screened for the production of antibacterial and antifungal compounds against a panel of gram-negative and gram-positive bacteria, mycobacteria, yeasts and fungi. A total of 28 species displayed antibacterial activity, of which six also showed antifungal activity. Asparagopsis taxiformis and Cymopolia barbata were the species with the strongest activities against the broadest spectrum of target microorganisms. All the species with antibacterial activity were active against gram-positive bacteria, whereas only two species, A. taxiformis and Osmundea hybrida, were active against mycobacteria. The production of secondary metabolites with antimicrobial activities by the macroalgae was also studied under different conditions, although no common trend for bioactivity was observed. PMID- 11770819 TI - Lectin activity of Lentinus edodes. AB - The hemagglutinating activity of submerged mycelium and culture liquid for four strains of Lentinus edodes (Berk.) Sing [L. edodes (Berk.) Pegler] was studied in the search for lectins. The hemagglutinating activity of culture liquid was substantially higher, compared with mycelium. The carbohydrate-binding capacity of the agglutinins was established, and the lectin activity of extracts from mycelia grown on several agar media was elucidated in relation to fruiting. The lectin activity of L. edodes was examined at different morphogenetic steps: mycelium, brown mycelial film, primordium, and fruiting body. Hemagglutination titers at the brown film step were higher than in the mycelium, whereas activity at the primordial and fruiting bodies steps decreased. Lectins seem to be involved in the formation of hyphal aggregates of brown mycelial film. PMID- 11770820 TI - Vladimir I. Vernadsky (1863-1945), founder of the biosphere concept. PMID- 11770821 TI - Recent findings in the modern RNA world. AB - It is assumed that modern life forms arose from a molecular ancestor in which RNA molecules both stored genetic information and catalyzed biochemical reactions. In modern cells, these functions are carried out, respectively, by DNA and proteins, but diverse cellular RNAs are also involved in key cellular functions. In this paper, we review the cellular RNAs that are ubiquitous and/or that perform essential biological functions, and we discuss the evolutionary relationships of such RNAs with a prebiotic RNA world. This unexpected biological diversity of cellular RNAs and the crucial functions they perform in cellular metabolism demonstrate the complexity of an RNA-driven metabolism in an ancient RNA world and in modern life. Cellular RNAs are involved in translation (tRNA and rRNA) but also in ribosome maturation (snoRNA) and more generally in RNA processing (snRNA and snoRNA), replication (telomerase RNA), editing, protein translocation (SRP RNA), cellular transport (vRNA) and translation quality control (tmRNA). In addition, the function of many other cellular RNAs has not yet been determined. Future investigations of RNA function will allow us to better understand not only early evolutionary biological processes but also the central metabolism of modern cells. PMID- 11770822 TI - Bergey's manuals and the classification of prokaryotes. PMID- 11770823 TI - Learning about microbiology: virus or bacteria? PMID- 11770824 TI - Cells, disease, and genotypes: the revolution of molecular medicine. PMID- 11770825 TI - Roger Yate Stanier, 1916-1982: a transcendent journey. AB - The Tenth International Symposium on Phototrophic Prokaryotes (Barcelona, 26-31 August 2000) was the latest in a series of conferences initiated by Roger Stanier in 1971 to create ties within the community of scientists working with cyanobacteria or green and purple bacteria. Consonant with Stanier's own work, the subjects of these conferences range broadly from systematics and ecology through genetics, biochemistry and physiology. The effort to define comprehensively the place of bacteria in the living world was the leitmotif in Stanier's work, the subject of one of his earliest papers (in 1941), and revisited for the final time in his autobiographical memoir of 1980. Salvador Luria noted that Stanier "...always pursued broad naturalistic interests along with chemical ones, deliberately emphasizing morphology and ecology side by side with biochemistry." Chronologically, Stanier's work addressed taxonomic and nutritional aspects of the cytophagas, enzyme induction and patterns of regulation of enzyme synthesis, aromatic degradative pathways, characterization of what would subsequently be called 70S bacterial ribosomes, the regulation of bacteriochlorophyll synthesis by nonsulfur purple bacteria, protection by carotenoids against photooxidative damage, the path of carbon in heterotrophy, the molecular basis of streptomycin dependence, the life cycle of Caulobacter, the taxonomy of pseudomonads, and, for the last 12 years of his life, wide ranging studies of the cyanobacteria. PMID- 11770826 TI - Evolution of the genomic systems of prokaryotes and its momentous consequences. AB - The earliest self-reproducing cell on Earth, our common ancestor, was probably as small as present-day bacteria. It gave rise to a very large and durable clone whose descendants must have been the only living occupants of the oceans for about one thousand million years. They reached astronomical numbers of separate, disjunct cells, and synthesized many new genes. Their small volume could not accommodate ever larger genomes and useful new genes replaced resident, less successful sequences, thus increasing diversity and the number of strains with highly specialized, distinct, bioenergetic potentialities. Also, selective pressure favored strains able to participate successfully in division of labor and in the sharing of diverse abilities in mixed communities, counterbalancing the limited capacities of individual genomes. Lateral gene transfer mechanisms appeared and were progressively improved, furthering the development of diversity. The prokaryotes' constructive evolution resulted in the formation of a worldwide web of genetic information, and a global bacterial superbiosystem (superorganism). By contrast, eukaryotic evolution of organisms has been typically Darwinian. Diversification of eukaryotic organisms was, however, considerably enriched and accelerated by symbioses with prokaryotes. The more broadly diversified bioenergetic potential of prokaryotes considerably increased the diversity of eukaryotes. Without their participation, our biosphere would have remained much less diverse and less dynamic. Environmental homeostasis has been maintained all along by guided bacterial evolution. PMID- 11770827 TI - Adaptation of bacterial communities to environmental transitions from labile to refractory substrates. AB - The aim of this work was to assess the adaptation of bacterial communities to environmental transitions from labile to refractory substrates. This involved testing the hypothesis that bacteria self-organize and propagate not only as individual cellular systems, but also as functional sets of interacting organisms. A biofilm community was cultivated in a flow-cell irrigated with tryptic soy broth and subjected to a cyclic series of environmental transitions, from labile to refractory substrates, followed by a period of starvation (30 days). The appearance and disappearance of specific colony morphotypes when the emigrants were plated onto tryptic soy agar was used to monitor the restructuring of the community. Confocal laser microscopy of flow cells showed that these transitions decreased the biofilm thickness and coverage. Substrate shifts also changed the architecture of the biofilm communities. Repeated inoculation of flow cell communities with a composite inoculum increased the number and diversity of emigrants. Their biofilms were thicker and covered a wider area than those of communities that had been inoculated only at the beginning of the experiment. With repeated inoculation, the time required for the community to restructure and stabilize decreased during most transitions. This suggested that organismal recombination acted as a mechanism of adaptation, enhancing the growth of microbial communities exposed to environmental stresses. Changes in the profiles of emigrants during the adaptation of biofilm communities to environmental transitions showed the appearance and disappearance of discrete sets of organisms. This suggested that the biofilm communities responded to environmental stresses as sets of interacting organisms. Enhanced growth of biofilm communities due to repeated environmental cycling suggested that the functionality of cellular positioning accrued from one cycle to the next and was thus heritable, although it was not necessarily genetically encoded. PMID- 11770828 TI - The eaeA gene is not found in Hafnia alvei from patients with diarrhea in Aragon, Spain. AB - A total of 102 Hafnia alvei clinical strains isolated from different patients with diarrhea has been tested, using polymerase chain reaction and dot-blot hybridization, for the enteropathogenic Escherichia coli attaching and effacing A (eaeA) gene to establish their role as a causative agent of diarrhea in our environment. None of them was positive for the eaeA gene. We cannot consider the eaeA gene as the virulence-associated factor implicated in the H. alvei strains isolated from diarrheal feces in our region. PMID- 11770829 TI - Potential of Burkholderia cepacia RQ1 in the biodegradation of heavy crude oil. AB - The potential of Burkholderia cepacia strain RQ1 in the biodegradation of heavy crude oil (Maya) was assessed to develop an active indigenous bacterial consortium for the bioremediation of crude oil-polluted systems in Nigeria. The heavy crude oil (Maya) was utilized as sole source of carbon, attaining maximum cell densities of 10(8) cfu ml(-1) from an initial 10(5) cfu ml(-1) in 15 days. Biomass also increased with oil concentrations up to 0.8% (w/v). Growth rates ranged from 0.028 h(-1) to 0.036 h(-1) and degradation rates decreased with increasing concentrations of oil from 0.009 day(-1) to 0.004 day(-1). The quantity of oil metabolized increased significantly (P < 0.05) with increasing concentrations of oil. However, the growth of the bacterium was inhibited at crude oil concentrations beyond 6% (w/v). The pH of the culture media also dropped significantly (P < 0.05) during the 15-day test period, while the non asphaltic fractions of the oil were significantly reduced (by about 89%) during the same period. The bacterium harbours a plasmid of about 10 kb that lacks restriction sites for the endonucleases Asp718, BamHI and PstI. PMID- 11770830 TI - Production of phenolics by immobilized cells of the lichen Pseudevernia furfuracea: the role of epiphytic bacteria. AB - Immobilized lichen cells from the thalli of the lichen Pseudevernia furfuracea, supplied with acetate as the only source of carbon, continuously produced phenolic substances, atranorin and physodic acid, over 23 days. Epiphytic bacteria associated with the lichen thallus grew actively, probably using both acetate and reduced compounds supplied by lichen cells, since their active growth was avoided by including 10 microM 3,3'-dichlorophenyl-1,1'dimethylurea in the bath solution. Penicillin largely impeded the growth of epiphytic bacteria and decreased phenolic production, which was recovered only at the end of the experimental period, just when the bacteria started a slow, but active growth. We suggest the cooperation of epiphytic bacteria in the biosynthesis of both atranotrin and physodic acid. PMID- 11770831 TI - Arundifungin, a novel antifungal compound produced by fungi: biological activity and taxonomy of the producing organisms. AB - Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island (South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain (a sterile fungus belonging to the Leotiales and an undetermined coelomycete). PMID- 11770832 TI - Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. AB - BACKGROUND: The human cytochrome P450 enzyme CYP3A4 is involved in the metabolism of many anticancer drugs. Since these drugs are usually administered in a polychemotherapy regimen, the objective of this study was to examine their inhibitory potency on CYP3A4 with regard to possible mutual drug interactions. METHOD: CYP3A4 activities in human liver microsomes from 2 donors were determined using the oxidation of the dihydropyridine denitronifedipine, a specific CYP3A4 substrate, at a concentration of 50 microM (= KM). Formation of the pyridine metabolite was measured using HPLC. Inhibitor concentrations used were 0.5, 5 and 50 microg/ml, except for cyclophosphamide and ifosfamide (0.5, 2.5 and 5 mg/ml) and for paclitaxel (0.05, 0.15, 0.5, 1.5 and 5 microg/ml). RESULTS: The following substances showed an inhibitory effect on CYP3A4 (IC50 values for the 2 microsome samples are parenthesized): cyclophosphamide (12.3/9.2 mmol/l), mafosfamide generated 4-OH-cyclophosphamide (152/163 [micromol/l), ifosfamide (3.6/2.5 mmol/l), vinblastine sulfate (20/44 micromol/l), vincristine sulfate (67/176 micromol/l), daunorubicin hydrochloride (206/200 micromol/l), doxorubicin hydrochloride (160/215 micromol/l), teniposide (64/84 micromol/l) and docetaxel (6.4/12.7 micromol/l). No inhibitory effect on CYP3A4 was observed with epirubicin, etoposide, paclitaxel, cytarabine, 5-FU, 6-mercaptopurine, methotrexate, cisplatin, carboplatin, bleomycin, busulfan, chlorambucil and mitomycin. CONCLUSION: Comparing IC50 values with plasma concentrations present during antineoplastic therapy, the agents cyclophosphamide, ifosfamide, vinblastine, teniposide and docetaxel could possibly cause clinical drug interactions by inhibition of CYP3A4. Some recently described clinical interactions with antineoplastic agents may be explained by these results. PMID- 11770833 TI - Montelukast and improvement of eczema: observations from a prescription event monitoring study in England. AB - OBJECTIVE: Montelukast is an orally administered cysteinyl receptor antagonist, approved for the treatment of asthma. There is pharmacological plausibility of its effectiveness in the treatment of other immunologically mediated conditions such as eczema and urticaria. The objective of this study was to determine whether there are any beneficial effects of montelukast on eczema and urticaria. METHOD: A non-interventional observational cohort study was conducted between February 1998 and December 1998 using Prescription-Event Monitoring (PEM). During PEM studies, patients are systematically identified from dispensed prescription data and questionnaires are sent to the prescribing general practitioner (GP) asking them to report events occurring during and after treatment. In this study, events reported as eczema or urticaria improved were identified. A simple questionnaire was sent to the GPs for additional information. RESULTS: The cohort comprised 15,612 patients, in which 16 reports of eczema or urticaria improved were identified. Questionnaires were sent to the GPs for additional information. Fifteen of the 16 questionnaires were returned. In 5 cases the GPs thought that there was an improvement of eczema or urticaria with montelukast treatment in patients who had history of longstanding eczema or urticaria. Of the remaining 11 cases there was an alternative explanation for the improvement of eczema or urticaria in 10 cases and one was unassessable. CONCLUSION: PEM is conducted to monitor the safety of medicines, and doctors report events including improvement in pre-existing conditions. Although the number of cases of improvement of eczema or urticaria in this cohort is small, there is a possibility that leukotriene inhibitors may be helpful in the treatment of these diseases. Further studies are needed to provide evidence as to whether montelukast will have a role in the treatment of these conditions. PMID- 11770834 TI - Lipid-lowering treatment in coronary artery disease: a survey in an ambulatory outpatient clinic. AB - OBJECTIVES: In controlled trials, HMG-CoA reductase inhibitors (statins) effectively reduced cardiovascular events in patients with coronary artery disease (CAD). However, recent pharmacoepidemiological studies indicate an underuse of statins in the target population. The objective of this study was to examine the extent to which CAD patients in Germany actually received statins under field conditions. METHODS: We evaluated the medical records of 296 patients referred to the cardiology outpatient clinic of the Frankfurt University Hospital by their general practitioner (GP) in the period 1995 to 1998. All patients had symptomatic, angiographically proven CAD, 142 had previous myocardial infarction. A diagnosis of dyslipidemia was taken from the records. Most patients were visited on more than 1 occasion. In all, we were able to access 296 records for a 1st visit, 76 records for a 2nd visit and 29 records for a 3rd visit and 16 records for > 3 visits. RESULTS: According to the entry criteria of the 4S Trial (total cholesterol 5.5-8.0 mmol/l or 212-311 mg/dl), 108 patients were deemed as eligible for lipid-lowering treatment, criteria of the LIPID Trial (4.0-7.0 mmol/l or 154-270 mg/dl) gave a yield of 190 patients. The actual treatment rate with a statin at the 1st visit was 34% (LIPID Group) and 40% (4S Group). At later visits, the treatment rates with statins increased to 63% (LIPID Group) and 79% (4S Group), due to advice given to the GP by the outpatient clinic. When the observation period was devided into 2 periods (04/95 - 01/97; 02/97 - 09/98), actual treatment rates (all visits) for the 4S Group were 43% and 38%, respectively, indicating no further "penetration" of the 4S Study in the therapy decision-making of the GPs. CONCLUSIONS: The data indicate that necessary treatment with a HMG-CoA reductase inhibitor is often withheld in the ambulatory setting. PMID- 11770835 TI - Comparison of the efficacy and safety of naproxen CR and nabumetone in the treatment of patients with osteoarthritis of the knee. AB - OBJECTIVE: To comparre the safety and efficacy of naproxen CR (1,000 mg once daily) with that of nabumetone (1,000 mg once daily) in the treatment of patients with symptomatic knee osteoarthritis(OA). METHODS: A total of 159 Korean patients (80 in the naproxen CR group and 79 in the nabumetone group) were enrolled in this 4-week, single-blind, controlled, randomized, parallel study and an intention-to-treat model was used for data analysis. Six efficacy parameters were measured: Lequesne index, visual analogue pain scale at rest and atactivity, patient's and physician's global assessment, and time to walk 50 feet. RESULTS: Significant improvement in all efficacy parameters except time to walk 50 feet occurred at Week 2 and Week 4 in both groups. Themean improvement from baseline at Week 2 and Week 4 for the efficacy variables was not different between naproxen CR and nabumetone group. Twenty-four patients (30%) in the naproxen CR group and 18 patients (22.8%) in the nabumetone group withdrew from the study. Among them, only 1patient in the naproxen CR group terminated the study prematurely due to an adverse event of dyspepsia. No statistically significant difference in the frequency of adverse events, including gastrointestinal symptoms, was observed between these 2 groups during the treatment period. Significant laboratory abnormalities also did not occur during the study period in both groups. CONCLUSIONS: Naproxen CR is an effective and tolerable drug in the treatment of knee OA. Efficacy and safety profiles are comparable to those of nabumetone. PMID- 11770836 TI - Alfacalcidol in the therapy of renal bone disease. AB - Parathyroid hormone increases due to hypocalcemia even in the early phases of renal insufficiency. At the same time, hyperphosphatemia develops due to decreasing renal excretion which, in turn, intensifies secondary hyperparathyroidism. The cornerstones for prevention and therapy of renal osteopathy are, therefore, efficient lowering of phosphate levels and the early substitution of vitamin-D3 metabolites. In a post marketing surveillance (PMS) of almost 2,000 dialysis patients with renal osteopathy, the course of therapy with Alfacalcidol (Bondiol) was observed over a 6-month period. In 55.9% of cases, Alfacalcidol was administered at a daily dose of 0.25 microg. In 26.6% of patients, Alfacalcidol was administered every second day at a dose of 0.25-1 microg/d. In 16.1% of patients, Alfacalcidol was administered as pulse-therapy, mostly at a dose of 1-2 microg once or twice per week. To lower phosphate levels, 54.8% of patients received calcium compounds, 9.2% aluminium compounds, and 21.7% aluminium compounds in combination with calcium compounds. 14.3% of patients did not receive phosphate binding agents. Two thirds of patients had received active vitamin-D3-metabolites prior to commencing therapy with alfacalcidol, most frequently calcitrol. In 58.1%, the dialysis solution used had a calcium concentration of 1.5 mmol/l (44.8%) or lower; whereas in 41.9%, a higher calcium concentration was used--mostly 1.75 mmol/l (3 8%). During the observation period, serum concentrations of calcium and phosphate remained constant, suggesting that the risk of hypercalcemia due to therapy with Alfacalcidol was not increased. It was found that elevated alkaline phosphatase and parathyroid hormone levels could be significantly lowered (statistically). These effects could be observed both in patients who had been previously treated with vitamin-D3-metabolites and in patients without prior therapy. Efficacy and tolerability of therapy with Alfacalcidol was assessed to be very high by the attending nephrologists. PMID- 11770837 TI - Effects of fibrates on plasma prothrombotic activity in patients with type IIb dyslipidemia. AB - OBJECTIVE: Increased levels of fibrinogen and plasminogen activator inhibitor 1 (PAI-1) are associated with an increased risk of ischemic coronary disease and its complications. Since atherogenic dyslipidemias are well-known risk factors for coronary heart disease, this study aimed to determine whether Type IIb dyslipidemia, one of the most atherogenic dyslipidemias, is accompanied by increased PAI-1 and fibrinogen synthesis. The additional aim of this study was to evaluate the effect of micronized fibrates on the levels of PAI-1 and fibrinogen in patients with Type IIb dyslipidemia. SUBJECTS: Thirty patients with Type IIb dyslipidemia and 12 age-matched control subjects were studied. Fourteen patients were treated with fenofibrate and 16 were treated with ciprofibrate for 1 month. METHODS: Plasma PAI-1 levels were measured by the ELISA method with Diagnostica Stago kit. The level of fibrinogen was measured by the Clauss method. RESULTS: PAI-1 levels in dyslipidemic patients before treatment differed significantly in both the fenofibrate and ciprofibrate treatment groups (101.18 +/- 36.47 ng/ml, 87.64 +/- 32.06 ng/ml, respectively) from those in the control group (32.32 +/- 7.39 ng/ml, p < 0.001). Compared with the control subjects (2.91 +/- 0.35 g/l), fibrinogen levels before treatment were higher in patients with dyslipidemia treated with ciprofibrate (3.42 +/- 0.59 g/l, NS) and fenofibrate (3.65 +/- 1.10 g/l, p < 0.05). One-month ciprofibrate treatment resulted in an insignificant decrease in PAI-1 levels (76.28 21.60 ng/ml, NS) and in a significant decrease in fibrinogen levels (2.73 +/- 0.40 g/l, p < 0.01). After one-month fenofibrate treatment PAI-1 levels (81.22 +/- 25.01 ng/ml, p < 0.01) and fibrinogen levels (2.95 0.72 g/l, p < 0.01) decreased significantly. CONCLUSION: Type IIb dyslipidemic patients have increased levels of PAI-1 and fibrinogen. Micronized fibrates decreased not only lipid levels but also the levels of fibrinogen and PAI-1 in these patients. PMID- 11770838 TI - Effect of colestimide on intestinal absorption of ursodeoxycholic acid in men. AB - Colestimide is a new anion-exchange resin which is used to lower serum cholesterol levels in Japan. Because of its excellent compliance, colestimide can replace cholestyramine in the treatment of pruritus. However, there may be an interaction in cholestatic patients undergoing treatment with ursodeoxycholic acid (UDCA). Therefore, we studied the effect of colestimide on the absorption of UDCA in men. Five healthy men took two 100 mg tablets of UDCA after a test meal following an overnight fast, and blood samples were collected every 30 min for 3 h. Two weeks later, the same study was repeated just after taking colestimide granules (1.5 g). Bile acid subfractions in serum were measured by HPLC. Serum UDCA levels after 30 min (mainly unconjugated), which reflect the initial absorption, were decreased > 50% by colestimide in 4 out of 5 subjects. Serum total bile acid levels after 30 min, which reflect the initial absorption of bile acids due to postprandial bile secretion, were decreased by colestimide in all subjects. These results indicate that colestimide administration before the meal inhibits UDCA absorption. PMID- 11770839 TI - Meta-analysis of beta-blockers in heart failure. PMID- 11770840 TI - Microspectrofluorometry of autofluorescence emission from human leukemic living cells under oxidative stress. AB - Image cytometry was applied to study the intracellular localization of autofluorescence and the influence of an oxidative stress on this emission. K562 erythroleukemia cancer cells were analyzed with a microspectrofluorometer, coupled with a Argon laser (Ar+) (363 nm). From each cell, 15 x 15 emission spectra were recorded in the 400-600 nm spectral range to generate a spectral image of autofluorescence. The intracellular locations of the autofluorescence emission and of the specific mitochondrial probe rhodamine 123 (R123) were matched. Under a 363 nm excitation, all spectra from K562 cells show equivalent profiles with a 455 nm maximum emission, near of reduced nicotinamide adenine dinucleotide-(Phosphate) solution (NAD(P)H) (465 nm maximum emission). The spatial distribution of autofluorescence is homogeneous and different from the one of R123. Hydrogen peroxide (H2O2) (200 microM) and menadione (Men) (5 microM) induce a weak spectral change and a decrease in autofluorescence intensity, down to 40% of the initial emission. Doxorubicin (Dox) induces a dose-dependent decrease in autofluorescence emission and a release of intracellular free radicals. When cells were pre-treated 1 h with 1 mM glutathione (GSH), Dox induces a lower free radicals release, no significant variation of autofluorescence intensity and a lower growth inhibitory effect. Images cytometry of autofluorescence suggest that the intracellular NAD(P)H would not be restricted to mitochondrial compartments. The release of free radicals was associated with a decrease in autofluorescence intensity, mainly attributed to NAD(P)H oxidation both inside and outside mitochondria. PMID- 11770841 TI - Description of the fully mature oocyte of Drosophila melanogaster. AB - We detected fully mature undescribed oocytes in Drosophila melanogaster ovaries. The fully mature oocytes were rehydrate in ovaries. In the oocyte of stage 14, chromosomes make globular mass, while the chromosome shows meiotic metaphase I in fully mature oocytes. Both mature oocytes and stage 14 oocytes were activated by hypotonic treatment. When the mature oocytes or the stage 14 oocytes were activated, telophase II figures were observed in former oocytes but meiosis in latter oocyte stopped at late metaphase I, suggesting the stage 14 activated oocyte cannot pass the second checkpoint of meiosis. PMID- 11770842 TI - Nuclear transport of photosensitizers during photosensitization and oxidative stress. AB - The nuclear transport pathways of the photosensitizers meso-tetra(4 sulfonatophenyl)porphyrin (TPPS4) and meso-tetra(4-N-methylpyridyl)porphyrin (TMPyP) during photosensitization and oxidative stress were characterized in CT 26 murine colon carcinoma cells using fluorescence microscopy and multi-pixel spectral imaging. Prior to irradiation, TPPS4 and TMPyP localized mainly in the lysosomes, while irradiation or H2O2 treatment induced a relocalization into the nucleus and nucleoli. Flow cytometry analysis of isolated nuclei from the treated cells showed an increase in nuclear fluorescence accompanying the relocalization. Isolation and separation of the nuclear proteins according to molecular weight was performed using a sephadex G-100 column. The protein fractions exhibiting high fluorescence were separated by high performance liquid chromatography. Five major classes of proteins with a retention time of 1, 7, 11, 12 and 15 min were obtained. Each photosensitizer was associated with a distinct class of proteins. While TPPS4 fluorescence was detected in the protein fraction with a retention time of 11 min, TMPyP fluorescence was associated with a protein fraction having a retention time of 7 min. We conclude that although oxidative stress triggers entry into the nucleus of both TPPS4 and TMPyP, each sensitizer uses a distinct transport mechanism based on its chemical properties. PMID- 11770843 TI - Crustacean visual system: an investigation on glial cells and their relation to extracellular matrix. AB - Glial cells in higher invertebrate groups are usually recognized on the basis of their location and general morphological or functional criteria. In this study of the crustacean visual system, we have approached the analysis of the relations between glial cells and the extracellular matrix by classical histochemical methods for carbohydrates at the light and electron microscopic levels, carbonic anhydrase histochemistry and by the biochemical characterization of sulphated polysaccharides. Periodic acid-Schiff-positive glial cells and processes were observed in the retina, basement membrane below the retina and in the optic ganglia. Carbonic anhydrase was not detected in the retina but it was demonstrated in all optic ganglia. The biochemical analysis of the extracellular matrix confirmed the alcian blue reaction and showed that sulphated polysaccharides are not abundant in the optic neuropils. This article describes into more details the crustacean visual system glial cells classification, and the relation between them and the extracellular matrix. In addition, they show that glial cells are the main components of the retinal basement membrane. PMID- 11770844 TI - Spatial and temporal distribution of atrial natriuretic factor in the rat testis. AB - The atrial natriuretic factor (ANF) is a cardiac hormone whose gene and receptor are widely expressed in extracardiac tissues and organs. ANF induces its biological effects by binding to its specific guanylyl-cyclase-A receptor, which synthesizes the intracellular second messenger cGMP. Increasing evidences indicate that the testis shows the highest reactivity of stimulation of guanylate cyclase by ANF. The well-established functionally active ANF receptors in seminiferous tubules raise the question of the origin and function of ANF in the testis. Therefore, the current study was carried out to investigate the spatial and temporal distribution of ANF in the rat testis by use of immunocytochemistry. Our immunocytochemical results showed that at different pre- and postnatal ages of testicular development ANF was constantly expressed in Leydig cell cytoplasm. However, the intensity of immunoreaction varied between the different Leydig cell populations (fetal, progenitor and immature) and apparently depends on the acquisition of testosterone producing ability. In seminiferous tubules ANF staining was established in the cytoplasm of the developing spermatocytes, in degenerating germ cells (23-day of age) in the cytoplasm of Sertoli cells, cap phase of acrosomal development and in the spermatids (55-day of age). The observed staining patterns suggest a broader spectrum of ANF activities and a possible participation in the whole process of regulation of germ cell development. Our data provide additional support for the hypothesis that ANF plays a major role in autocrine/paracrine regulation of the rat male gonad. PMID- 11770845 TI - Reorganization of chromatin in Xenopus egg extracts: electron microscopic studies. AB - The structural basis of mitotic condensation of chromosomes is one of the problems of cell biology yet to be elucidated. A variety of approaches have been used to study this problem and a large number of hypotheses have been proposed to explain the different levels of compaction of chromatin. Xenopus egg extracts, now widely used to study various aspects of cell biology, provide a valuable tool to study mitotic condensation of chromosomes. No detailed study has however yet been reported on the submicroscopic organization of condensed chromosomes in vitro in egg extracts. We present here the results of our electron microscopic studies on the organization of condensed chromosomes in vitro, using demembranated sperm nuclei and mitotic (CSF-arrested) extracts of Xenopus laevis eggs, clarified by high speed centrifugation. Upon introduction of sperm nuclei in egg extracts, the nuclei swell and the chromatin undergoes a rapid decondensation; at this stage the chromatin is formed of 10 nm fibrils. After longer incubation, the chromatin condenses, and by 2 h chromosomal structures can be visualized by staining with DAPI or Hoechst 33258. Our results on the organization of chromosomes in different stages of condensation are discussed in relation to the different hypotheses proposed to explain the process of mitotic condensation of chromosomes. Finally, this study demonstrates the feasibility of high-resolution analysis of the process of chromosome condensation. PMID- 11770846 TI - Studies on composition and stability of a large membered bacterial consortium degrading phenol. AB - A ten member microbial consortium (AS) consisting of eight phenol-degrading and two non-phenol-degrading strains of bacteria was developed and maintained in a fed-batch reactor by feeding 500 mg l(-1) phenol for four years at 28 +/- 3 degrees C. The consortium could degrade 99% of 500 mg l(-1) phenol after 24 hours incubation with a biomass increase of 2.6 x 10(7) to 4 x 10(12) CFU ml(-1). Characterization of the members revealed that it consisted of 4 principal genera, Bacillus, Pseudomonas, Rhodococcus, Streptomyces and an unidentified bacterium. Phenol degradation by the mixed culture and Bacillus subtilis, an isolate from the consortium was compared using a range of phenol concentrations (400 to 700 mg l(-1)) and by mixing with either 160 mg l(-1) glucose or 50 mg l(-1) of 2,4 dichlorophenol in the medium. Simultaneous utilization of unrelated mixed substrates (glucose/2,4-dichlorophenol) by the consortium and Bacillus subtilis, indicated the diauxic growth pattern of the organisms. A unique characteristic of the members of the consortia was their ability to oxidize chloro aromatic compounds via meta pathway and methyl aromatic compounds via ortho cleavage pathway. The ability of a large membered microbial consortia to maintain its stability with respect to its composition and effectiveness in phenol degradation indicated its suitability for bioremediation applications. PMID- 11770847 TI - Microorganisms asssociated with Withania somnifera leaves. AB - Microorganisms including bacteria, actinomycetes and fungi were recovered from the leaves of Withania somnifera, which were collected from two altitudinal ranges (0-300 m and 1700-2000 m) in the Asir region, Saudi Arabia. Types and numbers of microorganisms varied according to the altitude and the month of collection. The number of microorganisms was higher on old leaves than that on young ones in most cases. Low altitude exhibited more microorganisms than high altitude. The relationship between meteorological factors and type and number of the recovered microorganisms is discussed. Inoculation of detached healthy leaves of Withania by all recovered fungal species revealed only Alternaria solani as a pathogen of this plant. To confirm pathogenicity, scanning and transmission electron microscopic examination revealed the colonization of this pathogen inside the leaf tissue. Penetration of Withania leaves by the fungus occurred only through stomata, and the invading hyphae were located in the intercellular spaces of leaf tissues. Ultrastructural changes noted in infected cells included changes in chloroplasts and the invagination of the host plasma membrane. PMID- 11770848 TI - Perchlorate and nitrate reductase activity in the perchlorate-respiring bacterium perclace. AB - The perchlorate (ClO4(-))-respiring organism, strain perclace, can grow using nitrate (NO3(-)) as a terminal electron acceptor. In resting cell suspensions, NO(-) grown cells reduced ClO4(-), and ClO4(-) grown cells reduced NO3(-). Activity assays showed that nitrate reductase (NR) activity was 1.31 micromol min(-1) (mg protein)-1 in (ClO4)- grown cells, and perchlorate reductase (PR) activity was 4.24 micromol min(-1) (mg protein)(-1) in NO3(-) grown cells. PR activity was detected within the periplasmic space, with activities as high as 14 pmol min(-1) (mg protein)(-1). The NR had a pH optimum of 9.0 while the PR had an optimum of 8.0. This study suggests that separate terminal reductases are present in strain perclace to reduce NO3(-) and ClO4(-). PMID- 11770849 TI - Diagnosis of nocardiosis by polymerase chain reaction: an experimental study in mice. AB - In this study, we have established a sensitive semi-nested polymerase chain reaction (PCR) for detection of Nocardia in clinical specimens by first amplifying a 422 bp DNA fragment from the groEL gene, followed by a second amplification of 342 bp DNA by targeting sequences internal to the first amplicon. The semi-nested PCR was evaluated in a murine model of nocardiosis for detection of Nocardia in blood and visceral organs. Healthy BALB/c mice were intravenously infected with 0.2 ml suspension of 2.9 x 10(5)/ml cfu of Nocardia asteroides and N. farcinica. Viable counts and seminested PCR were performed post infection with samples of blood as well as lung, liver, spleen, kidney and brain at 5 minutes, 3 h, and then every 24 h for 3 days. Of the 20 blood samples tested, 15 (75%) were Nocardia positive by culture and 19 (95%) were positive by semi-nested PCR. Likewise, in case of N. asteroides infection, 46% organ samples were positive by culture and 58% by semi-nested PCR. The positivity of organ samples was higher with N. farcinica, 60% by culture and 72% by PCR, which may be attributed to its increased virulence as compared to N. asteroides. These results demonstrate that semi-nested PCR is a rapid and sensitive method for detection of Nocardia in blood and different visceral organs. The diagnostic application of this method provides an additional advantage over culture techniques, as PCR can also detect L-forms of Nocardia in clinical specimens, which otherwise fail to grow on routine isolation medium. PMID- 11770850 TI - Degradation of poly (3-hydroxybutyrate) and its copolymer poly (3-hydroxybutyrate co-3-hydroxyvalerate) by a marine Streptomyces sp. SNG9. AB - A marine Streptomyces sp. SNG9 was characterized by its ability to utilize poly(3 hydroxybutyrate) (PHB) and its copolymer poly(3-hydroxybutyrate-co-3 hydroxyvalerate P (3HB-co-HV). The bacterium grew efficiently in a simple mineral liquid medium enriched with 0.1 % poly(3-hydroxybutyrate) powder as the sole carbon source. Cells excreted PHB depolymerase and degraded the polymer particles to complete clarity in 4 days. The degradation activity was detectable by the formation of a clear zone around the colony (petri plates) or a clear depth under the colony (test tubes). The expression of PHB depolymerase was repressed by the presence of simple soluble carbon sources. Bacterial degradation of the naturally occurring sheets of poly(3-hydroxybutyrate) and its copolymer poly(3 hydroxybutyrate-co-3-hydroxyvalerate) was observed by scanning electron microscopy (SEM). Morphological alterations of the polymers sheets were evidence for bacterial hydrolysis. PMID- 11770851 TI - Effect of epiphytes on the extent of necrotic injuries of resistant and susceptible poplar clones infected with Dothichiza populea. AB - Poplar cuttings of a resistant clone, Populus 'Grandis', and susceptible clones, Populus nigra 'Italica' and Populus 'Robusta', were infected with the pathogenic fungus Dothichiza populea alone, or with the pathogen and one of five strains of epiphytes antagonistic towards it (in vitro), isolated from poplar bark. The extent of injury was examined for 28 days after infection by determining the length of necrotic patches and their area as expressed in per cent of the total area of a cutting or the area of necrotic injuries caused by the pathogen alone. All the poplar cuttings of both the resistant and susceptible clones became diseased when infected with the pathogen alone. Surprisingly enough, however, the least affected clone was the susceptible P. 'Robusta', in which necrotic injuries covered 28% of the total area, as against 40% and 70% in the resistant P. 'Grandis' and the susceptible P. nigra 'Italica', respectively. When the cuttings were infected simultaneously with Dothichiza populea and its antagonistic epiphytes, the diseased area in the resistant clone diminished by as much as two thirds, and in the susceptible P nigra 'Italica', by one-third in comparison with the area affected by the pathogen alone. In turn, in the susceptible P. 'Robusta' the introduction of three out of five epiphytes stimulated the growth of the pathogenic fungus producing on average a double increase in the necrotic area. The differences in the response of the pathogen to the presence of epiphytes recorded in the susceptible clones indicate a marked influence of the plant on the nature of interactions between its epiphytic microflora and the pathogen. PMID- 11770852 TI - Motility and chemotactic response of Pseudomonas fluorescens toward chemoattractants present in the exudate of Macrophomina phaseolina. AB - Pseudomonas fluorescens strains (LAM1-hydrophilic) and (LAM2-hydrophobic) showed positive chemotaxis towards attractants (sugars, amino acids, polyols and organic acids) present in the exudate of Macrophomina phaseolina (a soil-borne plant pathogenic fungus). The varied response of motility traits such as speed, rate of change in direction (RCDI) and net to gross displacement ratio (NGDR) was observed for different chemoattractants. Swimming speed of the strains was highest in 10-fold diluted exudate or 100-1000 microM strength of different attractants, but further dilutions significantly decreased the swimming speed (P = 0.05). Chemotactic response of P fluorescens was positively correlated with swimming speed (P = 0.05; r = 0.76). Relative to control, the RCDI values decreased 1.5-fold in amino acids or sugars, and 1.2-fold in polyols or organic acids. With increase in swimming speed, the NGDR of both strains also increased, but the RCDI decreased. Both hydrophilic and hydrophobic strains did not show significant differences in their motility traits. The results demonstrate that M. phaseolina exudate contains chemical attractants that serve as signal for flagellar motility of P. fluorescens. Motile P fluorescens strains thus may consume fungal exudate as nutrients, and thus spores could offer a niche for these bacteria in soil. PMID- 11770853 TI - Chitinolytic and cellulolytic Pseudomonas sp. antagonistic to fungal pathogens enhances nodulation by Mesorhizobium sp. Cicer in chickpea. AB - Pseudomonas strains isolated from the rhizosphere of chickpea (Cicer arietinum L.) and green gram (Vigna radiata L.) were screened for the production of chitinases and cellulases. Five Pseudomonas strains were found to produce appreciable amounts of both enzymes in culture-free supernatants and showed growth inhibition of the two fungi Pythium aphanidermatum (Oomycete) and Rhizoctonia solani (Basidiomycete) in plates on potato dextrose agar medium. The fungal growth inhibition was not correlated with cell wall-degrading enzyme activity, which suggested that other antifungal compounds produced by these rhizobacteria were also involved in antagonism. Coinoculation of the Pseudomonas strains with the Mesorhizobium sp. Cicer strain Ca 181 resulted in a significant increase in nodule biomass when grown under sterilized chillum jar conditions. The results suggest that hydrolytic enzymes produced by Pseudomonas sp. contribute to suppression of plant diseases by inhibiting growth of phytopathogenic fungi and also promote nodulation of legumes by rhizobia. PMID- 11770854 TI - Measurement of the viability of arbuscular-mycorrhizal fungi using three different stains; relation to growth and metabolic activities of soybean plants. AB - Histochemical staining of alkaline phosphatase (ALP) and succinate dehydrogenase (SDH) activities in four arbuscular mycorrhizal fungi (Glomus intraradices, G. fasciculatum, G. monosporum and G. mosseae) and their relation to growth and metabolic activities of soybean plants were investigated in a greenhouse experiment. In general, mycorrhizal inoculation significantly increased the growth responses, phosphorus and nitrogen contents, acid and alkaline phosphatases as well as total soluble protein of soybean compared to non mycorrhizal plants. Stimulation was related to the viability of each mycorrhizal fungus. The localization of succinate dehydrogenase (as a vital stain of metabolically active fungus) and alkaline phosphatase activity (as a potential marker of efficiency of the symbiosis) in the arbuscular mycorrhizal fungi were variable. The activity appeared in young arbuscles and intercellular hyphae, whereas the collapsed arbuscules were inactive. The histochemical staining results demonstrated that the activity of alkaline phosphatase fungi was lower than succinate dehydrogenase. The use of nitroblue tetrazolium chloride as a vital stain for SDH activity showed that all mycorrhizal infection revealed by trypan blue staining was not physiologically active. Thus, the possible utilization of these enzymes to assess the activity of mycorrhizal fungi and its relation with effectively for plant growth and mineral contents is discussed. PMID- 11770855 TI - Production of viral progeny in insect cells undergoing apoptosis induced by a mutant Anticarsia gemmatalis nucleopolyhedrovirus. AB - The Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV) is the most successful viral biopesticide in use worldwide. We have demonstrated that despite widespread apoptosis and no protein synthesis at 48 h p.i., UFL-AG-286 cells infected with a mutant of AgMNPV (vApAg), produced significant amounts of budded virus (BVs) and viral DNA late in infection. However, a different susceptible cell line (BTI-Tn5B 1-4) showed no signs of apoptosis and produced 3.5 times more budded virus when infected with vApAg. A comparison of DNA from AgMNPV and vApAg digested with the same restriction enzymes showed differences in the restriction pattern, indicating that the vApAg phenotype might be due to a mutation in a gene or genes responsible for directly or indirectly inhibiting apoptosis in UFL-AG-286 cells. PMID- 11770856 TI - Dominant fungi in the rhizosphere of established tea bushes and their interaction with the dominant bacteria under in situ conditions. AB - Species of Penicillium and Trichoderma were found to dominate the rhizosphere of established tea bushes in a detailed study conducted from various tea growing locations in India. Penicillium erythromellis, P. janthinellum, P. raistrickii, Trichoderma pseudokoningii and T. koningii were found to be closely associated with tea roots. While seasonal fluctuation was observed in the case of Penicillium spp., the population of Trichoderma spp. showed less variation during the year. Both species were sensitive to low temperatures. In general, fungi associated with the tea rhizosphere were found to prefer a mesophillic temperature range (15 degrees C to 35 degrees C). The dominant species of Penicillium and Trichoderma also exhibited tolerance to lower temperatures, i.e., 5 to 10 degrees C on agar plates. Most fungi were able to grow in a wide range of pH (4 to 12). Lowering of soil pH in the rhizosphere of tea bushes was positively correlated with the age of the bush and may have affected the development of a specific microbial community in the rhizosphere. The populations of Penicillium and Trichoderma species were inversely correlated with the populations of two most dominant rhizosphere bacteria, Bacillus subtilis and B. mycoides. Both Bacillus species have been shown to have antagonistic activity against these two fungi under in vitro conditions. The present study demonstrates the existence of a similar antagonism under in situ conditions in the rhizosphere of established tea bushes. PMID- 11770858 TI - Production and characteristics of Debaryomyces hansenii killer toxin. AB - The optimal conditions for the production of the killer toxin of Debaryomyces hansenii CYC 1021 have been studied. The lethal activity of the killer toxin increased with the presence of NaCl in the medium used for testing the killing action. Production of the killer toxin was stimulated in the presence of proteins of complex culture media. Addition of nonionic detergents and other additives, such as dimethylsulfoxide enhanced killer toxin production significantly. Killer toxin secretion pattern followed the growth curve and reached its maximum activity at the early stationary phase. Optimal stability was observed at pH 4.5 and temperatures up to 20 degrees C. Above pH 4.5 a steep decrease of the stability was noted. The activity was hardly detectable at pH 5.1. PMID- 11770857 TI - Significance of physical attachment of fungi for bio-treatment of water. AB - The inhibitory effect of xenobiotics known to damage cell surface structures was studied. The sensitivity of suspended cells of the two fungi Candida maltosa and Fusarium proliferatum was compared with that of artificial or natural biofilms of these fungi. The results obtained indicate that the resistance of attached cell populations to model xenobiotics is increased compared with suspended cells. Only the attached fungal cells had the capacity to degrade acetone and phenol and to adapt to increasing concentrations of these substances, so they seem ideally suited for bioremediation of waste water. PMID- 11770859 TI - Inflammation and infarction: the explored, the unexplored and the individual response to inflammatory stimuli. PMID- 11770860 TI - Inflammatory mechanisms in atherosclerosis: from laboratory evidence to clinical application. AB - From the initial stages of leukocyte recruitment to diseased endothelium, to eventual rupture of unstable atheromatous plaque, pro-inflammatory mechanisms mediate key steps in atherogenesis and its complications. Lipid lowering, both with diet and statin therapy, has been shown to have favorable effects on inflammatory processes in atheromatous plaque. Several plasma markers of inflammation have been found to predict future cardiovascular risk, both among patients with acute coronary syndromes and myocardial infarction, and among healthy men and women. C-reactive protein (CRP), a pattern recognition molecule linked to the innate immune system, is a sensitive marker of low-grade vascular inflammation, which may also have direct pro-inflammatory actions. Recent studies have shown that statin therapy may lower CRP levels independent of lipid-lowering effects. Statin therapy may also be highly effective for the prevention of cardiovascular events among individuals with elevated CRP levels. The role of statin therapy for plaque stabilization in acute coronary syndromes, and for prevention of future plaque rupture among healthy individuals with evidence of vascular inflammation, is an area of active research. PMID- 11770861 TI - C-reactive protein and atherosclerosis: quo vadis? AB - In recent years numerous studies have demonstrated a direct association between elevated levels of C-reactive protein (CRP) and future risk of cardiovascular disease. An intriguing question is whether CRP represents just a sensitive marker of systemic inflammation, a process known to play an important role in atherothrombogenesis, or whether it may contribute actively to atherosclerotic lesion formation. In this paper we summarize the current evidence for an involvement of CRP in atherogenesis and we speculate about potential therapeutic implications these observations might have. PMID- 11770862 TI - C-reactive protein and its role in the pathogenesis of myocardial infarction. AB - C-reactive protein (CRP), the classical acute phase reactant, has for some time contributed to both the diagnosis and management of a wide range of infective and inflammatory conditions. More recently with the advent of high sensitivity assays, the hypothesis that atherosclerosis is an inflammatory disease has been strengthened. "Elevated" CRP values predict a poor outcome for patients suffering from unstable coronary syndromes as well myocardial infarction, and large epidemiological surveys have shown that baseline values of CRP can predict future cardiovascular events in those at risk, as well as those otherwise well. Increasingly a direct role for CRP in the pathogenesis of atherosclerosis and post-myocardial infarction inflammation has also been suggested, and CRP itself may prove to be a future therapeutic target in the treatment of atherosclerosis and its consequences. PMID- 11770863 TI - Platelet function and arterial thrombosis. PMID- 11770864 TI - Platelet receptor polymorphisms and thrombotic risk. AB - Plaque rupture and/or endothelial damage lead to exposure of von Willebrand factor and collagen which facilitate the adhesion of circulating platelets via glycoprotein Ib-IX-V and the integrin alpha2 beta1, respectively, to the damaged vessel wall. This process activates the platelet and leads to a conformational change of a second integrin alphaIIb beta3 that facilitates fibrinogen binding and platelet aggregation. Thrombin generated at the blood-plaque interface converts fibrinogen to fibrin, which stabilizes thrombus growth. Therefore, any genetic differences that might alter surface expression or activity of these receptors could influence risk for adverse outcomes as a result of the haemostatic process. In the last 5 years, there has been a rapid accumulation of the literature concerning the relationship between genetic variations in platelet glycoproteins and risk for coronary heart disease. In this chapter, we present a comprehensive review of the impact of platelet receptor polymorphisms and thrombotic risk. PMID- 11770865 TI - Platelet receptors for adhesion and activation. Variability as a factor in susceptibility to cardiovascular diseases. AB - Polymorphisms in coagulation factors leading to altered susceptibility to cardiovascular diseases have been known for some time and some are now well established risk factors. More recently, an increasing number of polymorphisms have been identified in platelet receptors and a series of studies indicate that these too may play a role as individual risk factors for stroke and myocardial infarction. The effect of these platelet polymorphisms appears less clear-cut than some of the coagulation factor effects and other, associated, risk factors may be important in defining their role. In this review platelet receptor polymorphisms and their role as risk factors are surveyed and their possible relevance discussed. PMID- 11770866 TI - Platelet regulation of thrombin generation in cardiovascular disease. AB - Platelets are intimately involved in the events leading to cardiac ischemia through their release of bioactive substances, aggregation, and support of procoagulant reactions at sites of atherosclerotic plaque formation and rupture. This review article will focus on what is currently known about the regulation of thrombin generation on the surface of activated platelets, and how it relates to thrombus formation. PMID- 11770868 TI - A new therapeutic strategy for electrical cardioversion of atrial fibrillation. AB - BACKGROUND: The conventional approach to cardioversion of atrial fibrillation includes a period of anticoagulation with oral anticoagulant therapy (OAT) extending from 3 weeks precardioversion to 4 weeks postcardioversion. The protocol of rapid anticoagulation (such as that of the ACUTE study) consists of a precardioversion transesophageal echocardiography (TEE) followed by OAT for 4 weeks. In the last few years low-molecular-weight heparins have established themselves as a safe and efficacious alternative to traditional antithrombotic therapies. The aim of this study was to demonstrate that the exclusion of thrombi by precardioversion TEE together with the exclusion of atrial stunning by a second TEE performed after 1 week, to date not suggested in the literature, could reduce to 7 days the period of pericardioversion anticoagulation. This therapy would be carried out using low-molecular-weight heparins with no need for biological monitoring and with the possibility of self-administration. METHODS: We have studied 57 consecutive patients who had atrial fibrillation or flutter with a history of atrial fibrillation lasting > 48 hours. All patients received enoxaparin at a dosage of 100 IU antiXa/kg twice daily before undergoing multiplane TEE. Previous informed consent and ethical committee authorization had been obtained. Twenty-four hours following TEE, in the absence of thrombi and/or spontaneous moderate/severe echocontrast in the atrial chambers, the patients underwent electrical cardioversion and were discharged within 24 hours of sinus rhythm restoration. These patients were prescribed enoxaparin at the indicated dosage twice daily until TEE, performed in an outpatients setting 7 days following cardioversion. In the absence of thrombi and/or atrial and/or left atrial appendage stunning, OAT was terminated. Enoxaparin was associated with OAT for the following 3 weeks if any of the following signs of stunning were present: A wave inferior to the normal value for age at transmitral Doppler; a left atrial appendage emptying velocity < 40 cm/s; the appearance or increase in the severity of spontaneous echocontrast. For all patients, clinical and electrocardiographic follow-up was carried out at 1 month. RESULTS: In one patient TEE was not tolerated and one refused it. In 7 patients cardioversion was not performed: 4 because of the presence of thrombi, 1 because of moderate/severe spontaneous echocontrast and 2 owing to spontaneous cardioversion. Of the remaining 48 patients, cardioversion proved to be efficacious in 38, with sustained sinus rhythm at 1 week in 33 patients. One of these refused the second TEE and of the remaining 32 patients, 24 (75%) showed no signs of stunning at the second TEE and so anticoagulation was terminated. Thus, after 1 week, 75% (24/33) of patients in sinus rhythm could benefit from a shortened anticoagulation therapy which lasted for a mean of only 8.5 days. No patients showed signs of a thromboembolic accident at 1 and 2 months of follow-up. CONCLUSIONS: Most patients undergoing electrical cardioversion for atrial fibrillation could benefit from a shorter period of anticoagulation with low-molecular-weight heparins for 1 week if TEE precardioversion and 7 days postcardioversion excludes thrombi and atrial stunning. The management of patients with atrial fibrillation would be greatly simplified. PMID- 11770867 TI - Inhibition of platelet recruitment by endothelial cell CD39/ecto-ADPase: significance for occlusive vascular diseases. AB - During their 7-9 day lifespan in the circulation platelets are mainly responsible for maintaining the integrity of the vasculature. In thrombocytopenic states, there is an increase in vascular permeability and fragility, presumably due to absence of this platelet function. In sharp contrast, biochemical or physical injury in the coronary, carotid or peripheral arteries induces platelet activation and platelet recruitment, which can culminate in thrombotic vascular occlusion. Since there is one death every 33 s from vascular occlusion in the United States, this situation constitutes a major public health issue. In the course of studying interactions between cells of the vascular wall and those in the circulation, we observed that platelets in close proximity to endothelial cells do not respond to agonists in vitro. Experiments initiated in the late 1980's cumulatively indicated that endothelial cell CD39--an ecto-ADPase--was mainly responsible for this phenomenon. CD39 rapidly and preferentially metabolizes ADP released from activated platelets. ADP is the final common pathway for platelet recruitment and thrombus formation, and platelet aggregation and recruitment are abolished by CD39. Our current hypothesis is that CD39 will be a novel antithrombotic agent for treating high risk patients who have activated platelets in their circulation--the identifying characteristic of coronary artery occlusion and thrombotic stroke. A recombinant, soluble form of human CD39 has been generated. This is solCD39, a glycosylated protein of 66 kDa whose enzymatic and biological properties are identical to the full-length form of the enzyme. In our in vitro experiments, solCD39 blocks ADP-induced human platelet aggregation, and inhibits collagen- and thrombin receptor agonist peptide-induced platelet reactivity. We studied solCD39 in vitro in a murine model of stroke, which was shown to be driven by excessive platelet recruitment. In studies with CD39 wild-type (CD39+/+) mice solCD39 completely abolished ADP induced platelet aggregation, and strongly inhibited collagen- and arachidonate induced platelet reactivity ex vivo. When solCD39 was administered prior to transient intraluminal middle cerebral artery occlusion, it reduced ipsilateral fibrin deposition, decreased (111)In-platelet deposition, and increased post ischemic blood flow 2-fold at 24 hours. These results were superior to those we obtained with aspirin pre-treatment. CD39 null (CD39-/-) mice, which we generated by deletion of exons 4-6 (apyrase conserved regions 2-4), have a normal phenotype, normal hematologic profiles and bleeding times, but exhibit a decrease in post-ischemic perfusion and an increase in cerebral infarct volume when compared to genotypic CD39+/+ controls in our stroke model. "Reconstitution" of CD39 null mice with solCD39 reversed these pathologic changes. Thus, the CD39-/- mice were actually rescued from cerebral injury by solCD39, thereby fulfilling Koch's postulates. These experiments have led us to hypothesize that solCD39 has potential as a novel therapeutic agent for thrombotic stroke. In this review, we summarize our recent research results with CD39 and solCD39, and discuss our viewpoints on its present and future possibilities as a novel treatment for thrombosis. PMID- 11770869 TI - Effect of sildenafil citrate upon myocardial ischemia in patients with chronic stable angina in therapy with beta-blockers. AB - BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy. PMID- 11770870 TI - Rheumatic fever recurrence: a possible cause of restenosis after percutaneous mitral valvuloplasty. AB - BACKGROUND: We evaluated the occurrence of a rapid process of restenosis after percutaneous mitral valvuloplasty (PMV), initiated by the recurrence of acute rheumatic fever. Restenosis after PMV has been mainly related to a high echocardiographic score (> or = 8) indicating a severely compromised mitral valve apparatus. METHODS: From 1986 to 1996, 120 patients underwent PMV by the transseptal approach at our Institution. The mean follow-up time was 58 +/- 32 months (range 3 months to 9 years). RESULTS: Restenosis occurred in 10 patients (8.3%): in 4 restenosis was found within a relatively short period of time (1 to 3 months) following a documented recurrence of acute rheumatic fever; in the other 6 patients there was a gradual loss of the initial gain in the mitral valve area. CONCLUSIONS: These data suggest two potential mechanisms of restenosis: 1) a more common slow process, due to turbulent flow-trauma on the mitral valve; 2) a rapid process that relates to valvulitis consequent to a recurrence of acute rheumatic fever. In consideration of the second possibility, after PMV prophylactic treatment may be warranted at least in those patients who are at high risk of streptococcal infection. PMID- 11770871 TI - The use over time of statins in coronary patients in an Italian tertiary referral center. AB - BACKGROUND: In the last decade, large-scale clinical trials have consistently shown that therapy with statins is of great benefit to patients with and at risk of developing coronary artery disease. We assessed, in a sample of patients with coronary artery disease in whom coronary angiography was indicated and hospitalized in the last 10 years, the use of statins at admission. METHODS: One hundred patients with stable coronary artery disease were randomly selected per year from 1991 to 2000. The final study population consisted of 1000 patients. The prescription of statins for > or = 6 months before hospital admission was determined from a hospital-wide clinical database. RESULTS: From 1995, the prevalence of patients treated with statins at hospital admission progressively increased. In 1991, only 2% of patients were treated with statins before hospital admission while in the year 2000, 38% of patients were receiving this treatment. The mean prevalence of patients treated with statins before and after 1995 was 3 vs 22% (p < 0.0001) respectively. The distribution of the demographic and clinical parameters and the prevalence of conventional cardiovascular risk factors were similar in patients treated or not treated with statins. CONCLUSIONS: After 1994, in coincidence with the publication of the results of clinical trials showing the benefit of statins in patients with coronary artery disease, the use of these drugs increased significantly. This finding suggests that the widespread diffusion of the results of the major clinical trials and of guidelines drawn up by medical associations have had a significant impact on statin prescription in patients with coronary artery disease. Nevertheless our data also indicate that, despite overwhelming evidence on the benefits of statin therapy, in current clinical practice cardiologists are not optimally utilizing lipid management and that statins are frequently prescribed without an appropriate analysis of risk factors. PMID- 11770872 TI - Interatrial septal aneurysm and genetic prothrombotic disorders: possible interaction in the pathogenesis of pediatric stroke. AB - Stroke in children is a rare condition and has a multifactorial etiology. The association between ischemic stroke in young adults and some minor cardiac abnormalities such as atrial septal aneurysm with or without interatrial shunting has recently been reported: however, the pathogenetic mechanism still remains unclear. Genetic and acquired prothrombotic disorders are also risk factors for cerebral ischemic events in children. We report a case of ischemic stroke in a 10 year-old female child who was heterozygous for the prothrombin G20210A variant and who presented with an atrial septal aneurysm associated with an interatrial shunt. We hypothesize that these risk factors play a synergic role but their relative importance and whether alone they can determine cerebral embolism remain to be determined. PMID- 11770873 TI - Images in cardiovascular medicine. Coronary spasm resistant to intracoronary nitrates following successful stent implantation. PMID- 11770874 TI - Endocrine disruptors--a controversy in science and policy: session III summary and research needs. PMID- 11770875 TI - Social, economic and cultural context influence the expression of exposure to neurotoxicants: session IV summary and research needs. PMID- 11770876 TI - Children's exposure to toxic chemicals--modeling their world to quantify the risks: session V summary and research needs. PMID- 11770877 TI - Roles of glia in developmental neurotoxicity: session VI summary and research needs. PMID- 11770878 TI - Advancing the science and practice of reducing risks to children--a perspective from NGOs. AB - This session focused on two areas: actions to help advance the science as well as practice of reducing rsks to children, and strategies for making partnerships between researchers, NGOs and others more productive. PMID- 11770879 TI - Astroglia as metal depots: molecular mechanisms for metal accumulation, storage and release. AB - The brain is an organ that concentrates metals, and these metals are often localized to astroglia. An examination of metal physiology of brain cells, particularly astroglia, offers insights into the developmental neurotoxicity of certain metals, including lead (Pb), mercury (Hg), manganese (Mn), and copper (Cu). Xenobiotic metals probably accumulate in cells by exploiting the normal functions of proteins that transport and handle essential metals. In addition, essential metals may become toxic by accumulating at levels that exceed the normal metal buffering capacity of the cell. This review considers the uptake, accumulation, storage, and release of two xenobiotic metals, Pb and Hg, as well as two essential nutrient metals that are neurotoxic in high amounts, Mn and Cu. Evidence that each metal accumulates in astroglia is evaluated, together with the mechanisms the host cell may invoke to protect itself from cytoxicity. PMID- 11770880 TI - Glia and fetal alcohol syndrome. AB - Glial cells and their interactions with neurons play vital roles during the ontogeny of the nervous system and in the adult brain. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in utero alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial-neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. In vivo studies have shown ethanol-associated alterations in the migration of neurons and radial glial as well as in astrogliogenesis and myelin development. In astrocytes in primary culture, ethanol has been found to (1) impair cell growth and differentiation, (2) decrease the levels of glialfibrillary acidic protein or GFAP (an astrocyte marker) and its gene expression and (3) interfere with the stimulatory effect of trophic factors affecting their release and receptor expression. Evidence also suggests that ethanol affects intracellular protein trafficking, which may mediate some effects of ethanol on astroglial cells. These findings suggest that glial cells are target of ethanol toxicity during brain development and may underlie the neurodevelopmental abnormalities observed after in utero alcohol exposure and in FAS. PMID- 11770881 TI - Aspartate and glutamate transport in acutely and chronically ethanol exposed neonatal rat primary astrocyte cultures. AB - Maintenance of the ionic and osmotic composition of the extracellular fluid (ECF) is essential for the optimal functioning of the central nervous system (CNS). Changes in ion and neurotransmitter levels in the cerebrospinal fluid (CSF) can have profound effects on the processing and transmission of neuronal signals. Cell swelling during correction of isotonic imbalances can produce a series of events leading to inappropriate release of excitatory amino acids (EAA). Given the osmoregulatory demands of the CNS, it is not surprising that it possesses well-developed osmoregulatory mechanisms capable of maintaining both extracellular and intracellular ionic composition and volume within narrow limits, despite large fluctuations in the ionic composition and osmolarity of the plasma. We have undertaken a series of studies to test the hypothesis that ethanol (EtOH) acts as an osmotic stressor and stimulates osmoregulatory processes in astrocytes. In the course of these studies, we have investigated the effects of acute and chronic exposure to EtOH on cell volume, as well as uptake and release of amino acids in neonatal rat primary astrocyte cultures. PMID- 11770882 TI - Astrogliosis in the adult and developing CNS: is there a role for proinflammatory cytokines? AB - Astrogliosis, characterized by the enhanced expression of GFAP, represents a remarkably homotypic response of astrocytes to all types of injuries of the CNS, including injuries of the developing CNS. As such, astrocytes serve as microsensors of the injured microenvironment regardless of their location in the CNS. The diversity of insults that engender astrogliosis and the brain-wide nature of the astrocytic response suggest that common injury factors serve as the trigger of this cellular reaction. One prominent theme that has emerged in recent years is that proinflammatory cytokines and chemokines serve as a stimulus for induction of astrogliosis. Here we present a brief critique of this hypothesis based on a review of literature and some of our own recentfindings. Studies of astrocytes, in vitro, clearly indicate that these cell types are responsive to a variety of growth factors, including cytokines and chemokines. A somewhat different picture, however, can be seen from data obtained in vivo. It is true that trauma and diseases of the nervous system, as well as some exposures to neurotoxic chemicals, can be associated with the expression in brain of large varieties of cytokines and chemokines. That these same conditions result in astrogliosis has fostered the circumstantial link between cytokine/chemokine expression and the induction of astrogliosis. Several lines of evidence argue against this view, including (a) suppression of cytokine expression does not suppress gliosis, (b) gliosis can occur in the absence of enhanced expression of cytokines, (c) elevations in brain cytokines can occur in the absence of gliosis and (d) the patterns of cytokine expression in the adult and developing CNS are more consistent with a trophic role for these chemical messengers rather than a role in the induction of inflammation. Enhanced expression of cytokines and chemokines after brain injury appear to be signal transduction events unrelated to the induction of astrogliosis. PMID- 11770883 TI - Microglia and macrophages in the developing CNS. AB - An understanding of microglial functions during normal CNS development is prerequisite for understanding developmental neurotoxicology. This review provides a brief summary of previous work regarding the origin of microglia and addresses differences and similarities between microglia and brain macrophages. Current concepts and ideas which implicate microglia in diverse developmental processes, such as apoptosis, axon growth, and vasculogenesis are discussed. The study of reactive microgliosis may prove useful in the histopathological analysis of neurotoxicant-induced brain damage during development. PMID- 11770884 TI - L1 cell adhesion molecule signal cascades: targets for ethanol developmental neurotoxicity. AB - A major mechanism guiding neural development is through cell-cell and cell-matrix adhesions and signaling mediated by cell adhesion molecules (CAMs). The majority of CAMs have been grouped into three families: the cadherins, the integrins and the members of the immunoglobulin superfamily including L1. While the elucidation of new receptors and matrix components has become a frequent occurrence, the elucidation of the mechanisms by which they operate, and the function of those mechanisms in complex developmental events remains rudimentary. Members of all three families participate in differential adhesion, signal transduction and physical/mechanical effects. Each of these modes of action is a potential target for developmental neurotoxicants. In this brief review, the role of L1 in normal and abnormal neurodevelopment will be summarized. L1 is a cell surface transmembrane glycoprotein with a single copy gene on the X chromosome. There are two alternatively spliced exons, with the RSLE containing form found only on axons and growth cones of post-mitotic neurons. L1 mediates the following functions: adhesion, neurite extension, neuronal migration, and axon fasciculation. L1 is critical for normal neural development; humans with genetic defects in L1, termed corpus callosum hypoplasia, mental retardation, adducted thumbs, spasticity and hydrocephalus (CRASH) syndrome, and mice lacking expression of L1 have extensive neuropathologic and aberrant behaviors. The observation that patients with fetal alcohol syndrome share similar features to patients with CRASH has lead to the investigation of the effects of ethanol on L1. Physiologic concentrations of ethanol have been shown to inhibit L1 mediated neurite outgrowth in cerebellar granule neurons. Such inhibition may result from decreased expression, altered cell surface distribution, impaired signal transduction, or impaired interaction with the cytoskeleton. These data indicate that L1 and its associated signaling pathways are potentially targets for developmental neurotoxicants. PMID- 11770885 TI - Molecular changes in glutamatergic synapses induced by Pb2+: association with deficits of LTP and spatial learning. AB - What are the molecular bases for the neurotoxicity that occurs after developmental exposure to low levels of Pb2+, and are these effects persistent and detrimental in adults? Our inability to understand specific mechanisms behind Pb2+ neurotoxicity has long been one of many problem areas of this preventable childhood disease. The sensitivity of the developing brain to Pb2+-induced neurotoxicity is an outcome of the many unique characteristics that comprise the developing central nervous system. The developing brain can be exposed to significant concentrations of Pb2+ during vulnerable periods of development such as synapse formation, gene and protein expression, and other diverse molecular changes associated with these processes. Recently, changes in NMDA receptor subunits were identified in animals that showed cognitive deficits induced by exposure to Pb2+. This molecular association is important because it provides new evidence in the characterization of developmental Pb2+ neurotoxicity that supports physiological findings of impairments in synaptic plasticity and behavior. This review updates information from molecular studies that can be directly associated with impairments of behavior and synaptic plasticity, and outlines the functional consequences of molecular differences in Pb2+-exposed animals that illuminate potential mechanisms of Pb2+-induced neurotoxicity. PMID- 11770886 TI - Future directions for neurobehavioral studies of environmental neurotoxicants. AB - Three proposals for enriching neurobehavioral toxicology studies are discussed. First, while IQ has proven useful as a primary endpoint, such apical measures are limited: they obscure important individual differences, tend to reflect the product rather than the process of learning, sample a limited range of intelligent behaviors, and are insensitive to critical outcomes such as learning disabilities. In terms of societal disease burden, behavioral and psychiatric morbidities might be even more important than cognitive morbidities. Such endpoints warrant careful attention. Second, the models of child development can be enriched, increasing our ability both to control for confounding bias and to evaluate potential modification of neurotoxicant effects by contextual factors. While the use of the Home Observation for Measurement of the Environment (HOME scale) and other measures of family-level proximal factors was an important advance, recent sociological work demonstrates the importance of broader conceptualizations of the ecology of child development (e.g. neighborhood and community characteristics). Third, much effort has been expended in attempts to identify the behavioral signature associated with exposure to a particular neurotoxicant. Given the limited success in identifying behavioral phenotypes even for well-characterized genetic disorders (e.g. Fragile-X, Williams, Velocardiofacial syndromes), the prospects seem grim for identifying specific and relatively invariant patterns in the expression of neurotoxicant effects across diverse dosing regimens and biological and cultural settings. In part this results from the likely influence of complex, but largely unknown, patterns of effect modification on the expressions of toxicity. Efforts to define the nature of these contingencies might be more productive than continued efforts to identify behavioral phenotypes. PMID- 11770887 TI - Development of a neurobehavioral battery for children exposed to neurotoxic chemicals. AB - In recent years there has been heightened concern over the potential impact of environmental exposures on neurological function in children. Children are thought to be especially vulnerable to neurotoxic effects due to a number offactors including play behavior, differences in metabolism, and the development state of the brain. Performance tests from the computerized Behavioral Assessment and Research System (BARS) and other non-computerized tests have been combined to develop a brief battery that assesses multiple neurobehavioral functions in preschool children aged 4-6. Tests were selected to assess a variety of cognitive functions including attention, memory, motor speed and coordination and other executive functions. The battery has also been translated into Spanish and developed for use with Latino populations. Four to six-year-old children are particularly challenging because of the shorter attention span and lower motivation to complete an extended test session. When testing this group it is important to maintain the motivation of the child throughout the entire session in order to obtain accurate performance measures. A series of sequential pilot studies were used to select and develop appropriate methods and parameters for the tests in the battery. Although English-speaking children were able to complete the initial battery with minimal difficulties, several difficulties were encountered when the tests were administered to a Latino population. Cultural differences made some material inappropriate for testing due to unfamiliarity with the material, and in some cases items in a test had more than one correct translation which made administration difficult. PMID- 11770888 TI - Contending with contradictory data in a risk assessment context: the case of methylmercury. AB - Two large sample, prospective longitudinal studies one in the Seychelles Islands in the Indian Ocean, the other in the Faroes Islands in the North Sea were conducted during the 1990s to examine the effects of prenatal methylmercury exposure on intellectual function in childhood. The Faroes study found evidence linking this exposure to adverse outcome, but the Seychelles study did not. A peer review workshop held in Raleigh, NC, in 1998 concluded that the inconsistencies between the Faroes and Seychelles findings could be explained by differences in study design and sources of exposure. The US Environmental Protection Agency contracted with the National Academy of Sciences (NAS) to convene an expert panel to provide guidance for a new risk assessment for methylmercury. The NAS panel reviewed the Faroes and Seychelles studies in light of data from a smaller New Zealand study and other data not available to the Raleigh reviewers. These additional data provided evidence of adverse effects in studies whose design and source of exposure were similar to that in the Seychelles, leading the NAS panel to conclude that the weight of the evidence supported the Faroes findings. A power analysis, conducted by computing standardized regression coefficients for the three studies, indicated that many of the Faroes findings were so subtle that the power to detect them in the Seychelles study, despite its large sample size, was only about 50%. Because prospective epidemiological studies are often hampered by limited control over confounding and other factors, including unmeasured between cohort differences in genetic vulnerability and nutritional adequacy, inferences about toxicity often depend heavily on a qualitative assessment of the weight of the evidence from multiple studies. PMID- 11770889 TI - Uncertainties in the reference dose for methylmercury. AB - This paper critically examines the National Academy of Sciences and the National Research Council report on the toxicological effects of methyl mercury and the recently published US Environmental Protection Agency Reference Dose (RfD) for Methylmercury. Particular scrutiny is placed on the choice of the critical study and the underlining assumptions utilized in the selection of specific uncertainty factors (UFs) and the rationale for using a less-than-default factor of 10. The UFs that were utilized or considered by other agencies and organizations are also critically examined, explained and compared to one another. Based on these analyses, the authors suggest research that could be performed that would ameliorate the uncertainty of choosing a more precise partial UFor that may even provide completeness of database to allow for selecting of a UF for unity, thus improving the precision of the current published RfD. PMID- 11770890 TI - Predicted mercury concentrations in hair from infant immunizations: cause for concern. AB - Mercury (Hg) is considered one of the worlds most toxic metals. Current thinking suggests that exposure to mercury occurs primarily from seafood contamination and rare catastrophic events. Recently, another common source of exposure has been identified. Thimerosal (TMS), a preservative found in many infant vaccines, contains 49.6% ethyl mercury (EtHg) by weight and typically contributes 25 microg of EtHg per dose of infant vaccine. As part of an ongoing review, the Food and Drug Administration (FDA) announced in 1999 that infants who received multiple TMS-preserved vaccines may have been exposed to cumulative Hg in excess of Federal safety guidelines. According to the centers for disease control (CDC) recommended immunization schedule, infants may have been exposed to 12.5 microg Hg at birth, 62.5 microg EtHg at 2 months, 50 microg EtHg at 4 months, 62.5 microg EtHg at 6 months, and 50 microg EtHg at approximately 18 months, for a total of 237.5 microg EtHg during the first 18 months of life, if all TMS containing vaccines were administered. Neurobehavioral alterations, especially to the more susceptible fetus and infant, are known to occur after relatively low dose exposures to organic mercury compounds. In effort, to further elucidate the levels of ethyl mercury resulting from exposure to vaccinal TMS, we estimated hair Hg concentrations expected to result from the recommended CDC schedule utilizing a one compartment pharmacokinetic model. This model was developed to predict hair concentrations from acute exposure to methymercury (MeHg) in fish. Modeled hair Hg concentrations in infants exposed to vaccinal TMS are in excess of the Environmental Protection Agency (EPA) safety guidelines of 1 ppm for up to 365 days, with several peak concentrations within this period. More sensitive individuals and those with additional sources of exposure would have higher Hg concentrations. Given that exposure to low levels of mercury during critical stages of development has been associated with neurological disorders in children, including ADD, learning difficulties, and speech delays, the predicted hair Hg concentration resulting from childhood immunizations is cause for concern. Based on these findings, the impact which vaccinal mercury has had on the health of American children warrants further investigation. PMID- 11770891 TI - Risk assessment under FQPA: case study with chlorpyrifos. AB - Key science policies have had significant impact on the evolving implementation of the Food Quality and Protection Act (FQPA) (PL 104-170, 1996) by the US Environmental Protection Agency (EPA). The impact offour of these policies will be examined using the risk assessment for chlorpyrifos as a case study. These policies are selection of a regulatory endpoint, use of animal data without consideration of human data for setting the reference dose, a 10 FQPA safety factor and use of the 99.9 percentile of modeled consumer exposure in the acute dietary assessment. Each of these policy decisions had individual impact that was then compounded as cumulative impact on the revised risk assessment for chlorpyrifos conducted by the US EPA in 2000 [Federal Register Notice 65(159) (2000) 49982]. But embedded within each science policy, there are assumptions which may be too conservative and which together have resulted in a very large multiplicative reduction in the allowable exposure limits for chlorpyrifos in the US. These new exposure limits are quite different from other regulatory standards around the world. There is third party opposition to many of these policies and many believe the understanding of the relationship between exposure and what is known about human and animal responses to chlorpyrifos has been clouded. These changes in policy insert a new level of conservatism into the scientific statement of risk and create confusion that threatens to weaken the credibility of the regulatory process. PMID- 11770892 TI - A Web-based survey method for evaluating different components of uncertainty in relative health risk judgments. AB - Uncertainty permeates the process of risk assessment. It arises from recognized sources such as inadequacy of toxicological data, lack of exposure information, and imprecise identification of sensitive populations. In addition to these ambiguities, comparative risk exercises, which amount to risk assessment on a scale wider than that applied to single agents, also entail balancing community values, cost-benefit analyses, and other factors not directly tied to toxicology. Such exercises often convene evaluation panels to attempt a ranking of different stressors or stressor groups. The size of these panels is necessarily limited, and they usually strive to reach some form of consensus on ranking. Because ordinal assignments of risk are so difficult to achieve, they actually evolve into rating agendas in which stressors are categorized as high, medium, or low risks. Whether ranking or rating is its aim, this process, with its emphasis on agreement, usually overlooks two major components of uncertainty. One is variability among raters in assigning a score or category. The other is the degree of uncertainty they implicitly attach to their individual ratings. Both serve as guides to the scope and clarity of the available information. To gather more information about these critical but usually overlooked contributions to uncertainty, and, simultaneously, to query a broader sample of respondents, a survey method was designed to exploit the possibilities of electronic communication based on the World Wide Web. This method can secure risk ratings of selected stressors from many different samples of respondents. In addition, it can also provide information about the extent of ratings variability among risk assessors, individuals, or groups of respondents, about the bases of the ratings, and, concurrently, the confidence they place in their judgment. Comparative risk endeavors conducted in this format make their aims and content easy to modify. Data obtained by such a method can serve as pointers to new research initiatives, to regulator priorities, or to further iterations. PMID- 11770893 TI - Immunohistochemistry for the prion protein: comparison of different monoclonal antibodies in human prion disease subtypes. AB - Demonstration of the abnormal form of the prion protein (PrP) in the brain confirms the diagnosis of human prion disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies in PrD subtypes including sporadic and variant Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Alzheimer's disease (AD), and control brains. CJD subgroups were determined using Western blot analysis for the protease-resistant PrP type in combination with sequencing to determine the genotype at the methionine/valine polymorphism at codon 129 of the prion protein gene. None of the antibodies labeled given subgroups exclusively, but the intensity of immunoreactivity varied among morphologically distinct types of deposit. Fine granular or synaptic PrP deposits stained weakly or not at all with antibodies against the N-terminus of PrP, and were visible in one case only with 12F10 and SAF54. Coarser and plaque type deposits were immunolabeled with all antibodies. The immunostaining patterns appear characteristic for the disease subgroups. Labeling of certain neurons in all cases irrespective of disease, and staining at the periphery and/or throughout the senile plaques of AD patients were also noted. Antibodies such as 6H4 and 12F10 failed to give this type of labeling and are therefore less likely to recognise non-pathological PrP material in immunohistochemistry. PMID- 11770894 TI - Genetic modeling of glioma formation in mice. AB - In addition to the histological features that define gliomas, mutations and other alterations in gene expression and signal transduction are classically found in these tumors. Some of these alterations are likely to be the effects of the neoplastic phenotype, while others may be causative agents essential to the etiologic origin of the disease. The determination of whether specific genetic alterations, either individually or in combination, can serve as the etiology of gliomas requires modeling in animals with the fulfillment of Koch's postulates. Animal modeling studies not only provide information on the potential causes of glioma formation, they also identify novel candidate targets for therapy and provide tumor-bearing animals for preclinical trials. Recently, remarkable strides have been made in the generation of mouse models of the diffuse gliomas that provide unparalleled opportunities for advancing our knowledge of the etiology, maintenance, and treatment of this lethal class of tumors. PMID- 11770895 TI - CD95-mediated apoptosis of human glioma cells: modulation by epidermal growth factor receptor activity. AB - The death ligands CD95L and Apo2L/TRAIL are promising investigational agents for the treatment of malignant glioma. EGFR is overexpressed in a significant proportion of malignant gliomas in vivo. Here, we report that CD95L-induced cell death is enhanced by EGFR inhibition using tyrphostine AG1478 in 7 of 12 human malignant glioma cell lines. Conversely, CD95-mediated and Apo2L-induced cell death are both inhibited by overexpression of EGFR in LN-229 cells. CD95L-induced cell death augmented by AG1478 is accompanied by enhanced processing of caspase 8. LN-229 cells overexpressing the viral caspase inhibitor, crm-A, are not sensitized to CD95L-induced cell death by AG1478, indicating that EGFR exerts its antiapoptotic properties through a caspase 8-dependent pathway. These data define a modulatory effect of EGFR-activity on death ligand-induced apoptosis and indicate that EGFR inhibition is likely to improve the efficacy of death ligand based cancer therapies. Furthermore, it is tempting to speculate that EGFR amplification protects tumor cells from death ligand-mediated host immune responses in vivo and that EGFR's effects on death receptor-mediated apoptosis may explain the anti-tumor effects of non-cytotoxic, unarmed anti-EGFR family antibodies. PMID- 11770896 TI - July 2001: 58-year-old man with a temporal bone mass. AB - The July 2001 Case of the Month (COM). A 58-year-old man with right ear hearing loss since childhood presented with a two year history of dizziness and vertigo. Neuroradiological studies showed a large mass arising from the petrous portion of the temporal bone. The lesion was resected and microscopic examination revealed a cholesterol granuloma with a small component of cholesteatoma. It is important to distinguish between cholesterol granuloma and cholesteatoma because of treatment differences. However, these two entities can occasionally be seen together and rare giant variants have been described. PMID- 11770897 TI - August 2001: Sellar/suprasellar mass in a 59-year-old woman. AB - The August 2001 COM. Symptomatic granular cell tumors (GCTs) of the neurohypophysis are rare lesions. They are generally regarded as benign neoplasms, although detailed descriptions of the natural course of the tumors are limited to a few cases. We report on a 59-year-old woman with a large GCT of the neurohypophysis and rapid onset of symptoms. Although lacking definitive signs of malignancy, the tumor showed nuclear polymorphism, proliferative activity, evidence of a mutation of the tumor suppressor gene p53 as well as expression of the apoptosis-inhibiting protein bcl-2. These indices may be useful in defining more precisely the clinicopathological prognosis for neurohypophyseal GCTs. PMID- 11770898 TI - September 2001: 51-year-old man with seizures since childhood. AB - The September 2001 COM. A 51 year old man with refractory seizures presented with a recent seizure while at work but no other neurologic deficit. Imaging studies demonstrated a solid and cystic lesion of the right temporal lobe. Microscopic and immunohistochemical studies demonstrated an atypical ganglioglioma due to the presence of neurofibrillary tangles within the neoplastic ganglion cell component. This is the fifth case reported in the literature. Neoplastic ganglion cells and neurofibrillary tangles are discussed both separately and as integral components of this rare tumor. PMID- 11770900 TI - Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. AB - We correlate chromosomal changes in medulloblastomas with histologic subtype, reporting the analysis of 33 medulloblastoma specimens by comparative genomic hybridization, and a subset by fluorescence in situ hybridization. Of the 33 tumors, 5 were desmoplastic/nodular, 10 were histologically classic, and 18 were large cell/anaplastic. Chromosomal gains and losses were more common in anaplastic medulloblastomas than in non-anaplastic ones. We identified 4 medulloblastomas with c-myc amplification and 5 medulloblastomas with N-myc amplification; all 9 were of the large cell/anaplastic subtype. Additional regions with high level gains included 2q14-22, 3p23, 5p14-pter, 8q24, 9p22-23, 10p12-pter, 12q24, 12p11-12, 17p11-12, and Xp11. The majority of these high level gains occurred in anaplastic cases. We also found loss of chromosome 17p in 7 large cell/anaplastic cases but no nonanaplastic medulloblastomas. Finally, we detected a significantly increased overall number of chromosomal alterations in large cell/anaplastic medulloblastomas (6.8/case) compared to non-anaplastic ones (3.3/case). These findings support an association between myc oncogene amplification, 17p loss, and large cell/anaplastic histology. PMID- 11770899 TI - The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease. AB - Alzheimer's disease (AD) and stroke are two leading causes of age-associated dementia. A rapidly growing body of evidence indicates that increased oxidative stress from reactive oxygen radicals is associated with the aging process and age related degenerative disorders such as atherosclerosis, ischemia/reperfusion, arthritis, stroke, and neurodegenerative diseases. New evidence has also indicated that vascular lesions are a key factor in the development of AD. This idea is based on a positive correlation between AD and cardiovascular and cerebrovascular diseases such as arterio- and atherosclerosis and ischemia/reperfusion injury. In this review we consider recent evidence supporting the existence of an intimate relationship between oxidative stress and vascular lesions in the pathobiology of AD. We also consider the opportunities for therapeutic interventions based on the molecular pathways involved with these causal relationships. PMID- 11770901 TI - Argyrophilic grain disease: neuropathology, frequency in a dementia brain bank and lack of relationship with apolipoprotein E. AB - Argyrophilic grain disease (AGD) is a recently recognized disorder whose relationship to dementia as well as genetic or biochemical features remain incompletely characterized in part due to diagnostic difficulties engendered by concomitant pathologies. In the present study, we reviewed a consecutive series of over 300 brains referred for evaluation of dementia for presence of argyrophilic grains (AGs). AGs were found in the hippocampal region and amygdala, and were accompanied by coiled bodies in the underlying white matter and ballooned neurons in the limbic lobe. Ballooned neurons were also found in the limbic lobe in a number of cases of advanced Alzheimer's disease (AD) that did not have AGs, supporting the lack of diagnostic significance of ballooned neurons confined to limbic lobe. The frequency of AGD in this series of dementia brains was 4.9% and was similar to the frequency in other autopsy series of nondemented cases, supporting the notion that there is no obligatory relationship between AGD and dementia. In the present series, ApoE epsilon4 allele frequency of AGD was dependent on concurrent AD, with AGD cases lacking AD similar to controls and cases with concurrent AD similar to AD. This suggests that AGD is an independent disease process from AD. PMID- 11770902 TI - Real-time quantitative polymerase chain reaction: a potential tool for genetic analysis in neuropathology. AB - Since its introduction in the early- to mid-1980s, the polymerase chain reaction (PCR) has been modified and optimized for an increasing number of applications. Early on, the focus was on the amplification of a specific nucleic acid template into quantities amenable to identification and experimental manipulation. While this remains an important application, recent technology has allowed the use of PCR to accurately quantitate the amount of a specific nucleic acid template present in a complex sample. Rather than simply analyzing the final product amount following the course of sequential cycles of amplification, quantitative PCR allows one to measure the accumulation of PCR product during the course of the reaction ("real-time PCR"). Under the appropriate conditions the number of PCR cycles required for the accumulation of a specific amount of product (during the exponential phase of the reaction) is a reflection of the relative amount of nucleic acid template present in the sample under analysis. Real-time quantitative PCR allows one to analyze a relatively large number of samples in a short period of time, potentially allowing multiple markers to be applied on a sample within a time frame consistent with clinical settings. In this overview, we will highlight the uses of real-time quantitative PCR as a potential diagnostic tool in neuropathology, focusing on the analysis of CNS tumors. PMID- 11770903 TI - Fluorescence in situ hybridization (FISH) in diagnostic and investigative neuropathology. AB - Over the last decade, fluorescence in situ hybridization (FISH) has emerged as a powerful clinical and research tool for the assessment of target DNA dosages within interphase nuclei. Detectable alterations include aneusomies, deletions, gene amplifications, and translocations, with primary advantages to the pathologist including its basis in morphology, its applicability to archival, formalin-fixed paraffin-embedded (FFPE) material, and its similarities to immunohistochemistry. Recent technical advances such as improved hybridization protocols, markedly expanded probe availability resulting from the human genome sequencing initiative, and the advent of high-throughput assays such as gene chip and tissue microarrays have greatly enhanced the applicability of FISH. In our lab, we currently utilize only a limited battery of DNA probes for routine diagnostic purposes, with determination of chromosome 1p and 19q dosage in oligodendroglial neoplasms representing the most common application. However, research applications are numerous and will likely translate into a growing list of clinically useful markers in the near future. In this review, we highlight the advantages and disadvantages of FISH and familiarize the reader with current applications in diagnostic and investigative neuropathology. PMID- 11770904 TI - Insulin-like growth factor binding protein 2: gene expression microarrays and the hypothesis-generation paradigm. AB - A major goal of modern medicine is to identify key genes and their products that are altered in the diseased state and to elucidate the molecular mechanisms underlying disease development, progression, and resistance to therapy. This is a daunting task given the exceptionally high complexity of the human genome. The paradigm for research has historically been hypothesis-driven despite the fact that the hypotheses under scrutiny often rest on tenuous subjective grounds or are derived from and dependent on chance observation. The imminent deciphering of the complete human genome, coupled with recent advances in high-throughput bioanalytical technology, has made possible a new paradigm in which data-based hypothesis-generation is the initial step in the investigative process, followed by hypothesis-testing. Genomics technologies are the primary source of the new hypothesis-generating capabilities that are now empowering biomedical researchers. The synergistic interaction between contemporary genomics technologies and the hypothesis-generation paradigm is well-illustrated by the discovery and subsequent ongoing study of the role of insulin-like growth factor binding protein 2 (IGFBP2) in human glioma biology. Using gene expression microarray technology, the IGFBP2 gene was recently found to be highly and differentially overexpressed in the most advanced grade of human glioma, glioblastoma. Based on this discovery, subsequent functional studies were initiated that suggest that IGFBP2 overexpression may contribute to the invasive nature of glioblastoma, and that IGFBP2 may exert its function via a newly identified novel binding protein. The IGFBP2 story is but one example of the power and potential of the new molecular methodologies that are transforming modern diagnostic and investigative neuropathology. PMID- 11770905 TI - Tissue microarrays: applications in neuropathology research, diagnosis, and education. AB - Tissue microarrays (TMAs) are composite paraffin blocks constructed by extracting cylindrical tissue core "biopsies" from different paraffin donor blocks and re embedding these into a single recipient (microarray) block at defined array coordinates. Using this technique, up to 1000 or more tissue samples can be composited into a single paraffin block. Tissue microarrays permit high-volume simultaneous analysis of molecular targets at the DNA, mRNA, and protein levels under identical, standardized conditions on a single glass slide, and also provide maximal preservation and utilization of limited and irreplaceable archival tissue samples. This versatile technique facilitates retrospective and prospective human tissue studies, animal tissue studies, and cell line cytospin cell block studies. In this review, we present the technical aspects of TMA construction and sectioning, validation aspects of the technique, TMA advantages and limitations, and a sampling of the broad range of TMA uses in modern neuropathologic clinical diagnosis, research, and education. A specific illustration of the most widely employed and increasingly important TMA application is also presented: confirmation via TMA-based immunohistochemistry of the differential expression of a marker (IGFBP2) initially identified by gene expression profiling to be overexpressed in glioblastoma. PMID- 11770906 TI - Malaria surveillance--United States, 1998. AB - PROBLEM/CONDITION: Human malaria is caused by one or more of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). The protozoa are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with endemic transmission. Cases occasionally occur that are acquired through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. REPORTING PERIOD: Cases with an onset of symptoms during 1998. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood smear are reported to local and state health departments by health-care providers and laboratory staff members. Case investigations are conducted by local and state health departments, and reports are sent to CDC through the National Malaria Surveillance System (NMSS). This report uses NMSS data. RESULTS: CDC received reports of 1,227 cases of malaria with onsets of symptoms in 1998, among persons in the United States and its territories. This number represents a decrease of 20.5% from the 1,544 cases reported during 1997. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 42.8%, 37.8%, 3.5%, and 2.1% of cases, respectively. More than one species was present in seven patients (0.6% of total). The infecting species was not determined in 162 (13.2%) cases. Compared with reported cases in 1997, reported malaria cases acquired in Africa increased by 1.3% (n = 706); those acquired in Asia decreased by 52.1% (n = 239); and those acquired in the Americas decreased by 6.5% (n = 229). Of 636 U.S. civilians who acquired malaria abroad, 126 (19.8%) reportedly had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Five persons became infected in the United States. One case was congenitally acquired; one was acquired by blood transfusion; and three were isolated cases that could not be epidemiologically linked to another case. Four deaths were attributed to malaria. INTERPRETATION: The 20.5% decrease in malaria cases during 1998 compared with 1997 resulted primarily from decreases in P. vivax cases acquired in Asia among non-U.S. civilians. This decrease could have resulted from local changes in disease transmission, decreased immigration from the region, decreased travel to the region, incomplete reporting from state and local health departments, or increased use of effective antimalarial chemoprophylaxis. In a majority of reported cases, U.S. civilians who acquired infection abroad had not taken an appropriate chemoprophylaxis regimen for the country where they acquired malaria. PUBLIC HEALTH ACTIONS TAKEN: Additional information was obtained from state and local health departments and clinics concerning the four fatal cases and the five infections acquired in the United States. Persons traveling to a malarious area should take a recommended chemoprophylaxis regimen and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and subsequently develops fever or influenza-like symptoms should seek medical care immediately; the investigation should include a blood smear for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Current recommendations concerning prevention and treatment of malaria can be obtained from CDC. PMID- 11770907 TI - Tacrolimus and pimecrolimus. Introduction. PMID- 11770908 TI - Pathophysiologic mechanisms in atopic dermatitis. AB - Atopic dermatitis is a common, chronic inflammatory skin disease that frequently predates the development of asthma and/or allergic rhinoconjunctivitis. Recent studies have provided new insights into how the complex interrelationship of genetic, environmental, and immunologic factors may contribute to the development of atopic dermatitis. This article examines some of the factors involved in chronic cutaneous inflammation in this disease. Greater understanding of the mechanisms that underlie the pathophysiology of atopic dermatitis may lead to improved treatment strategies for this increasingly common skin disease. PMID- 11770909 TI - Tacrolimus pharmacology and nonclinical studies: from FK506 to protopic. AB - Tacrolimus (FK506) is a calcineurin inhibitor with potent immunomodulating properties. It has been marketed worldwide since 1993-1994 for the rejection of liver and kidney transplants (Prograf). The pharmacologic properties of tacrolimus resulted in its development as an ointment for the treatment of atopic dermatitis. An outline of nonclinical pharmacology studies that provided a rationale for this development is presented. The key nonclinical toxicology safety studies that supported clinical efficacy/safety trials are also discussed. Taken collectively, these studies contributed to the marketing approval of 0.03% and 0.1% tacrolimus ointment (Protopic) as a first in class treatment for atopic dermatitis. PMID- 11770910 TI - Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. AB - The ascomycin macrolactam derivative pimecrolimus (Elidel, SDZ ASM 981; Novartis Pharma AG, Basel Switzerland) is a cell-selective inhibitor of inflammatory cytokines specifically developed for the treatment of inflammatory skin diseases, such as atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, and plaque-type psoriasis. It inhibits the production of inflammatory cytokines in T cells and mast cells and prevents the release of preformed inflammatory mediators from mast cells. Topically administered pimecrolimus is as effective as the high-potency corticosteroid clobetasol-17-propionate in a pig model of allergic contact dermatitis (ACD). Unlike clobetasol, however, it does not cause skin atrophy. Given orally, pimecrolimus is as potent or superior to tacrolimus (FK 506) in treating ACD in mice and rats. Pimecrolimus also effectively reduces skin inflammation and pruritus in hypomagnesemic hairless rats, a model that mimics acute signs of atopic dermatitis. Pimecrolimus shows only a low potential to impair systemic immune responses when compared with tacrolimus as shown in rats in (1) the localized graft-versus-host reaction, (2) the antibody formation to sheep red blood cells, and (3) kidney transplantation. Pimecrolimus permeates through pig skin in vitro at a 10-times lower rate than tacrolimus, indicating a lower potential for percutaneous absorption in vivo. The data suggest that pimecrolimus combines high anti-inflammatory activity in the skin with a low potential to impair systemic immune reactions. PMID- 11770911 TI - Safety of the new macrolide immunomodulators. AB - With the wide acceptance of cyclosporine in the treatment of skin disease, there has been an effort to find new immunomodulating agents with superior safety profiles for use in dermatology. Among the most promising of the classes are the new macrolide immunomodulators, including tacrolimus and pimecrolimus. Of these, only tocrolimus has had widespread use for nondermatologic indications, primarily solid organ transplantation. Both of these agents have been studied for inflammatory diseases of the skin. In this article, we review the systemic and topical toxicities of these macrolide immunomodulators. PMID- 11770912 TI - Tacrolimus clinical studies for atopic dermatitis and other conditions. AB - The first topical immunomodulator approved for human use, tacrolimus ointment (Protopic, Fujisawa, Healthcare, Inc, Deerfield, IL), has been shown to be effective and safe in the treatment of children (aged 2 years and older) and adults with atopic dermatitis (AD). Clinical trials conducted worldwide have involved 12,000 patients, with safety and efficacy data available for up to 3 years of treatment. In addition to its beneficial effects in the management of AD, topical tacrolimus has also been reported to be of benefit in other immunologically mediated skin diseases including: hand dermatitis, contact dermatitis, eyelid dermatitis, erosive lichen planus, steroid-induced rosacea, pyoderma gangrenosum, and graft-versus-host disease. This article reviews the clinical experience of topical tacrolimus in the treatment of AD and other skin conditions. PMID- 11770913 TI - Pimecrolimus cream 1%: a new development in nonsteroid topical treatment of inflammatory skin diseases. AB - Atopic dermatitis (AD) is one of a family of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and allergic contact dermatitis). Dermal inflammation and production of proinflammatory cytokines by activated T cells is a prominent and defining characteristic in all of these conditions. Corticosteroids, though effective and potent immunosuppressants, are associated with a number of systemic and local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981) is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1% is minimally absorbed into the circulation; thus, it has a low bioavailability-reducing the risk for systemic adverse effects. The efficacy and safety of pimecrolimus cream 1% has been well shown in diverse patient populations with inflammatory skin diseases in several well-controlled trials. Significant and rapid amelioration of the signs and symptoms of AD was established in 3 studies lasting 6 weeks each, evaluating 589 pediatric patients. In a 1-year study, pimecrolimus was applied at the first signs and symptoms of eczema to prevent the progression of AD to flares. Flares were prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or completely eliminating the need for topical corticosteroids during a 1-year treatment period. Results in pimecrolimus studies in chronic irritant hand dermatitis and chronic hand dermatitis of mixed causes indicate potential for use in these important diseases, and further study in these indications is warranted. PMID- 11770914 TI - Topical tacrolimus and pimecrolimus: future directions. AB - Topical tacrolimus ointment and pimecrolimus cream represent the first members of a new class of medications. Topical immunomodulators have been developed for the treatment of atopic dermatitis. Their superb safety profiles and excellent efficacy as anti-inflammatory agents make them attractive candidates to treat a host of other skin disorders. This article reviews published experiences that use them for psoriasis, seborrheic dermatitis, lichen planus, pyoderma gangrenosum and other diseases. Possible modifications to these compounds and novel untested applications are discussed. PMID- 11770915 TI - Brain activity mapping with functional MR imaging. PMID- 11770916 TI - Truly hybrid interventional MR/X-ray system: investigation of in vivo applications. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to provide in vivo demonstrations of the functionality of a truly hybrid interventional x ray/magnetic resonance (MR) system. MATERIALS AND METHODS: A digital flat-panel x ray system (1,024(2) array of 200 microm pixels, 30 frames per second) was integrated into an interventional 0.5-T magnet. The hybrid system is capable of MR and x-ray imaging of the same field of view without patient movement. Two intravascular procedures were performed in a 22-kg porcine model: placement of a transjugular intrahepatic portosystemic shunt (TIPS) (x-ray-guided catheterization of the hepatic vein, MR fluoroscopy-guided portal puncture, and x ray-guided stent placement) and mock chemoembolization (x-ray-guided subselective catheterization of a renal artery branch and MR evaluation of perfused volume). RESULTS: The resolution and frame rate of the x-ray fluoroscopy images were sufficient to visualize and place devices, including nitinol guidewires (0.016 0.035-inch diameter) and stents and a 2.3-F catheter. Fifth-order branches of the renal artery could be seen. The quality of both real-time (3.5 frames per second) and standard MR images was not affected by the x-ray system. During MR-guided TIPS placement, the trocar and the portal vein could be easily visualized, allowing successful puncture from hepatic to portal vein. CONCLUSION: Switching back and forth between x-ray and MR imaging modalities without requiring movement of the patient was demonstrated. The integrated nature of the system could be especially beneficial when x-ray and MR image guidance are used iteratively. PMID- 11770917 TI - Conventional and hydrocolonic US of the appendix with CT correlation performed by on-call radiology residents. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to assess the feasibility and accuracy of emergent hydrocolonic ultrasonography (US) performed by on-call residents in patients suspected of having appendicitis. MATERIALS AND METHODS: Thirty-one patients with a clinically equivocal diagnosis of appendicitis were prospectively evaluated with conventional US, hydrocolonic US, and appendiceal computed tomography (CT). Midlevel radiology residents performed the US examinations while they were on call. Sensitivity, specificity, and accuracy for diagnosing appendicitis were calculated for conventional and hydrocolonic US by using clinical outcome as the standard. Results of US and CT of the appendix were also correlated. Residents recorded their diagnostic confidence for conventional and hydrocolonic US. All patients were able to hold the rectally administered contrast material until completion of both hydrocolonic US and appendiceal CT. RESULTS: The sensitivity for detecting appendicitis with conventional US, hydrocolonic US, and appendiceal CT was 50%, 75%, and 100%, respectively. Specificity was 96%, 93%, and 93%, respectively. Identification of the normal and abnormal appendix improved from 13% (four of 31 patients) with conventional US to 35% (11 of 31 patients) with hydrocolonic US. The radiology residents' diagnostic confidence increased from 0.74 with conventional US to 0.83 with hydrocolonic US. CONCLUSION: Hydrocolonic US is a feasible addition to conventional US examination for patients suspected of having appendicitis. It improves sensitivity, increases radiology residents' confidence, and is well tolerated by patients. PMID- 11770918 TI - Cranial nerve clock. Part 1. A declarative memory paradigm. AB - RATIONALE AND OBJECTIVES: The authors performed this study to compare a declarative memory paradigm developed to help teach medical students about the cranial nerves with a traditional text-based approach. MATERIALS AND METHODS: The authors designed a clock-based paradigm to help medical students learn about the cranial nerves. To enhance memorization and related brain activation, the paradigm uses visual, spatial, and word associations in the context of an analog clock face. Twenty-one undergraduate students were randomly divided into two groups. Group T viewed traditional text slides, and group C viewed text slides followed by the corresponding cranial clock slides. Subjects were tested before and after these sessions. RESULTS: Group C performed significantly better than group T in learning the names of the cranial nerves and their correct order (P < .011). Recall of name, number, and function was better for 11 of 12 cranial nerves, with statistical significance reached for nerves III (P = .005), V (P = .04), and X (P = .03). CONCLUSION: Alternative teaching strategies may help improve declarative memory. PMID- 11770919 TI - Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task. AB - RATIONALE AND OBJECTIVES: The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. MATERIALS AND METHODS: Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. RESULTS: Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. CONCLUSION: A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm. PMID- 11770921 TI - A curriculum in cardiothoracic radiology for medical students, with goals and objectives. PMID- 11770920 TI - Machine classification of dental images with visual search. AB - RATIONALE AND OBJECTIVES: The authors performed this study to assess the performance of a computer-based classification system that uses gaze locations of observers to define the subspace for machine learning. MATERIALS AND METHODS: Thirty-two dental radiographs were classified by an expert viewer into four categories of disease of the periapical region: no disease (normal tooth), mild disease (widened periodontal ligament space), moderate disease (destruction of the lamina dura), and severe disease (resorption of bone in the periapical area). There were eight images in each category. Six observers independently viewed the images while their eye gaze position was recorded. They then classified the images into one of the four categories. A sample of image space was used as input to a machine learning routine to develop a machine classifier. Sample space was determined with three techniques: visual gaze, random selection, and constrained random selection. K analyses were used to compare classification accuracies with the three sampling techniques. RESULTS: With use of the expert classification as a standard of reference, observers classified images with 57% accuracy, and the machine classified images with 84% accuracy by using the same gaze-selected features and image space. Results of kappa analyses revealed mean values of 0.78 for gaze-selected sampling, 0.69 for random sampling, 0.68 for constrained random selection, and 0.44 for observers. The use of sample space selected with the visual gaze technique was superior to that selected with both random-selection techniques and by the observers. CONCLUSION: Machine classification of dental images improves the accuracy of individual observers using gaze-selected image space. PMID- 11770922 TI - Expertise: implications for radiological education. PMID- 11770924 TI - Current structure and purpose of the American Board of Radiology examination process. PMID- 11770925 TI - The academy of radiology research and the growth of NIH support for imaging research, 1995-2001. PMID- 11770923 TI - The perils of testing. PMID- 11770926 TI - Imaging of the olfactory system. AB - The olfactory system consists of the primary olfactory nerves in the nasal cavity, the olfactory bulbs and tracts, and numerous intracranial connections and pathways. Diseases affecting the sense of smell can be located both extracranially and intracranially. Many sinonasal inflammatory and neoplastic processes may affect olfaction. Intracranially congenital, traumatic, and neurodegenerative disorders are usually to blame for olfactory dysfunction. The breadth of diseases that affect the sense of smell is astounding, yet the imaging ramifications have barely been explored. PMID- 11770928 TI - Imaging evaluation of cranial nerves 3, 4, and 6. AB - Neuropathies of the oculomotor, trochlear, and abducens nerves may present with isolated or complex neurologic findings. An understanding of the anatomy of these cranial nerves as they traverse the brainstem, basilar cisterns, and cavernous sinus on their way to the orbit can assist in localizing the suggested site of pathology and help to focus imaging protocols. Differential diagnostic possibilities for specific anatomic locations are reviewed. PMID- 11770927 TI - Imaging of the optic nerve and visual pathways. AB - The visual pathway extends from the globes anteriorly to the occipital cortex posteriorly. A wide variety of disease processes may produce visual dysfunction. Because the optic nerve is a fiber tract of the brain covered by meninges, it can be affected by many of the same pathologic processes that occur in the brain and meninges. Physical examination and diagnostic tests of visual function performed by the clinician can frequently identify the anatomic location of the causative lesion in the patient with vision loss. This enables the radiologist to optimize the imaging evaluation of the patient. This article reviews the normal anatomy of the optic nerve and visual pathways, presents computed tomography (CT) and magnetic resonance (MR) imaging techniques for evaluation of these structures, and discusses the pathologic processes intrinsic to the optic nerve and visual pathways. PMID- 11770929 TI - The trigeminal nerve. AB - The trigeminal nerve is the largest of the cranial nerves, serving as a major conduit for sensory information from the head and neck and primarily providing motor innervation to the muscles of mastication. An understanding of the pathologic processes that may involve this nerve requires a detailed knowledge of its origin within the brain stem as well as its course intracranially. This article describes the neuroanatomy of the nerve and divides it into its various segments to provide a differential diagnosis of common and some uncommon pathologic processes. PMID- 11770930 TI - Three-dimensional visualization and physiologic evaluation of bile canaliculi in the rat liver slice by confocal laser scanning microscopy. AB - We evaluated the morphology and physiologic function of the bile canaliculi (BC) in the rat liver slice (RLS) by confocal laser scanning microscopy (CLSM). Lucifer yellow (LY) dye was injected into the RLS, and the distribution of LY was serially evaluated. After the injection of LY, hepatocytes were initially visualized, followed by visualization of the BC. There was no significant difference in the distribution of LY between zones 1 and 3 in the hepatic lobule. In zone 1, the reticular distribution of the BC was observed, whereas the part of BC was linearly visualized in zone 3 along the course of sinusoids. When changes in the bile canalicular fluorescence (BCF) were serially evaluated, the BCF was decreased to the minimal level (88% of the value obtained immediately after the LY injection) 10 min after the LY injection, and it tended to increase thereafter. The intralobular hepatocyte fluorescence (ILHF) was decreased to 58.9% of the initial value during the first 40 min. However, the ILHF was transiently increased 30 min after the LY injection, suggesting the possibility of reabsorption of LY by hepatocytes. Three-dimensional (3-D) reconstruction images of the BC facilitated the evaluation of the stereoscopic structure of BC. Confocal laser scanning microscopy facilitated the evaluation of structures and physiologic function of the BC. PMID- 11770931 TI - Application of the low-loss scanning electron microscope image to integrated circuit technology part II--chemically-mechanically planarized samples. AB - Chemical-mechanical planarization (CMP) is a process that gives a flat surface on a silicon wafer by removing material from above a chosen level. This flat surface must then be reviewed (typically using a laser) and inspected for scratches and other topographic defects. This inspection has been done using both the atomic force microscope (AFM) and the scanning electron microscope (SEM), each of which has its own advantages and disadvantages. In this study, the low-loss electron (LLE) method in the SEM was applied to CMP samples at close to a right angle to the beam. The LLEs show shallower topographic defects more clearly than it is possible with the secondary electron (SE) imaging method. These images were then calibrated and compared with those obtained using the AFM, showing the value of both methods. It is believed that the next step is to examine such samples at a right angle to the beam in the SEM using the magnetically filtered LLE imaging method. PMID- 11770932 TI - High-resolution analysis of engineered type I collagen nanofibers by electron microscopy. AB - Collagen nanofibers were generated at ambient temperature and pressure by electrospinning a 1 wt% solution of type I collagen and polyethylene oxide. Products were imaged with high-resolution scanning electron microscopy (HRSEM) at medium (approximately 30,000 x) and high magnifications (approximately 100,000 x) and with transmission electron microscopy (TEM). The capacity to produce collagen nanofibers may lead to the generation of extracellular matrix-based fabrics with applications in the fields of wound healing and tissue engineering. PMID- 11770933 TI - Rapid diagnosis of fungal infection of intravascular catheters in newborns by scanning electron microscopy. AB - Intravascular catheters carry a significant risk of becoming colonized with bacteria and fungi and are important risk factors of septicemia in premature neonates. The study was undertaken to evaluate whether scanning electron microscopy (SEM) examination of removed catheters can be useful in early diagnosis of plastic infection by Candida, providing information useful for initiation of an eventual therapy. The evolution of biofilms in 28 catheters (umbilical or central) implanted in 24 newborns for prematurity was studied by SEM and transmission electron microscopy (TEM). In 4 of 24 patients, SEM examination revealed the presence of Candida in form of yeast or hyphae. In one of these patients, TEM confirmed the presence of organisms. In each case, hemoculture and culture of the catheter itself confirmed the diagnosis. The study demonstrates that SEM can identify fungi in the biomaterials covering the catheter surface in a few hours, allowing an early diagnosis of plastic infection. PMID- 11770934 TI - Imaging of specimens at optimized low and very low energies in scanning electron microscopes. AB - The modern trend towards low electron energies in scanning electron microscopy (SEM), characterised by lowering the acceleration voltages in low-voltage SEM (LVSEM) or by utilising a retarding-field optical element in low-energy SEM (LESEM), makes the energy range where new contrasts appear accessible. This range is further extended by a scanning low-energy electron microscope (SLEEM) fitted with a cathode lens that achieves nearly constant spatial resolution throughout the energy scale. This enables one to optimise freely the electron beam energy according to the given task. At low energies, there exist classes of image contrast that make particular specimen data visible most effectively or even exclusively within certain energy intervals or at certain energy values. Some contrasts are well understood and can presently be utilised for practical surface examinations, but others have not yet been reliably explained and therefore supplementary experiments are needed. PMID- 11770935 TI - Reduction of charging effects using vector scanning in the scanning electron microscope. AB - We describe a vector scanning system to reduce charging effects during scanning electron microscope (SEM) imaging. The vector scan technique exploits the intrinsic charge decay mechanism of the specimen to improve imaging conditions. We compare SEM images obtained by conventional raster scanning versus vector scanning to demonstrate that vector scanning successfully reduces specimen charging artifacts. PMID- 11770936 TI - Measurement technique for the incident electron current in secondary electron detectors and its application in scanning electron microscopes. AB - A measurement technique for incident electron current in secondary electron (SE) detectors, especially the Everhart-Thornley (ET) detector, based on signal-to noise ratio (SNR), which uses the histogram of a digital scanning electron microscope (SEM) image, is described. In this technique, primary electrons are directly incident on the ET detector. This technique for measuring the correlation between incident electron current and SNR is applicable to the other SE detectors. This correlation was applied to estimate the efficiency of the ET detector itself, to evaluate SEM image quality, and to measure the geometric SE collection efficiency and the SE yield. It was found that the geometric SE collection efficiency at each of the upper and lower detectors of a Hitachi S 4500 SEM was greater than 0.78 at all working distances. PMID- 11770937 TI - Is CPD effective? PMID- 11770938 TI - Piercing issue. PMID- 11770939 TI - Outreach clinics. PMID- 11770940 TI - Outreach clinics. PMID- 11770941 TI - Outreach clinics. PMID- 11770942 TI - Questions, questions... PMID- 11770943 TI - 'Drop in' dentistry. PMID- 11770944 TI - 'Drop in' dentistry. PMID- 11770945 TI - Occlusal considerations in periodontics. AB - Periodontal disease does not directly affect the occluding surfaces of teeth, consequently some may find a section on periodontics a surprising inclusion. Trauma from the occlusion, however, has been linked with periodontal disease for many years. Karolyi published his pioneering paper, in 1901 'Beobachtungen uber Pyorrhoea alveolaris' (occlusal stress and 'alveolar pyorrhoea'). (1) However, despite extensive research over many decades, the role of occlusion in the aetiology and pathogenesis of inflammatory periodontitis is still not completely understood. PMID- 11770946 TI - Management of the deep carious lesion and the vital pulp dentine complex. AB - This article describes the relationship between the carious process and pulp dentine complex reactions. Where the balance between the two is in favour of the carious process and where conventional cavity preparation leads to a direct pulp exposure, the direct pulp cap technique is described. The success of the technique is addressed and more importantly an alternative technique for caries removal, namely stepwise excavation, is described which may lead to a reduced risk of carious exposure and the need for the direct pulp cap technique. PMID- 11770947 TI - Hypodontia, ankylosis and infraocclusion: report of a case restored with a fibre reinforced ceromeric bridge. AB - Retained primary molars without permanent successors often undergo progressive infra-occlusion, without predictable exfoliation. Early prophylactic removal, after assessment of root resorption and adjacent periodontal support loss as well as age of onset, is often indicated. This article describes the joint orthodontic restorative care of such a case and describes an alternative method of restoration using a fibre-reinforced ceromeric bridge. As well as a conservative preparation and good aesthetics, an overlay restoration provided a fully functional occlusion. PMID- 11770948 TI - A preliminary investigation of the microbiology and endotoxin content in the water reservoirs of benchtop non-vacuum autoclaves. AB - To determine the microbial content and endotoxin concentration in the water reservoirs of benchtop autoclaves used in general dental practice. DESIGN: The study was done in two stages. Firstly water samples were taken daily from the reservoirs of 20 autoclaves used in general dental practices for six days. The microbial content and endotoxin concentration was determined. Second the practitioners were instructed to wash and clean the reservoirs of the autoclaves each morning prior to refilling with fresh water. The reservoirs were sampled in the evenings after a day's use and the microbial content and endotoxin concentration determined. RESULTS: The total viable count of bacteria before cleaning varied from 2,300 - 8 x 10(4) cfu/ml and after from 0-40 cfu/ml. The endotoxin concentrations before cleaning varied from 360-2,200 EU/ml and after 0 80 EU/ml. CONCLUSIONS: The reservoirs of non-vacuum benchtop autoclaves can become severely contaminated with micro-organisms particularly Gram-negative bacteria. The endotoxin content of the reservoirs can get to high and unacceptable concentrations. Draining the water reservoir and cleaning on a daily basis reduces the microbial content and the endotoxin concentration to acceptable levels. PMID- 11770949 TI - A preliminary communication on whether general dental practitioners have a role in identifying dental patients with mental health problems. AB - OBJECTIVE: To examine whether general dental practitioners regard themselves as having a role in identifying dental patients with mental health problems. METHOD: Telephone interviews were conducted with, and postal questionnaires were sent to, a random sample (n = 94) of general dental practitioners on Health Authority lists within the Mersey Region. A total of 84 general dental practitioners responded, resulting in an 89% response rate. RESULTS: The majority of general dental practitioners had encountered patients with mental health problems (78% of interviewees, 56% of questionnaire responders). However, nearly half of the interviewees (46%) do not refer patients with mental health problems. When referrals to dental specialists were made, they tended to be regarding a physical manifestation rather than a psychological one. The majority of interviewees and questionnaire responders (55% and 82% respectively) expressed a 'positive' response to the development of a referral role. Nevertheless, there were some reservations concerning the practicalities of its development and implementation. CONCLUSION: The majority of general dental practitioners consider a role in identifying patients with possible mental health problems. This role might include, being able to identify patients with undiagnosed mental health problems, and being aware of dental conditions which may be caused by mental health problems. To achieve this, inter-professional co-operation between general dental practitioners and other health professionals requires development. PMID- 11770950 TI - Assessment of the use of problem-orientated, small-group discussion for learning of a fixed prosthodontic, simulation laboratory course. AB - AIM: To evaluate a simulation laboratory course that used student-centred small group problem-orientated discussion activities as the main medium of instruction. METHODS: A structured questionnaire using a six-point Likert scale with 30 statements relating to a fixed prosthodontics course was distributed to 4th-year and 5th-year students who had completed the course. RESULTS: A 93% response rate was achieved for both years with a mean score for the 4th-year being 94.2 (+/- 13.7) and the 5th-year 107.5 (+/-16.9). The differences between the scores of both years are highly significant (P = 0.0006) indicating that the 5th-year were more favourable about the course and learning approach used. Consistency and reliability of the questionnaire was judged reliable according to Cronbach's alpha (4th-year = 0.7, 5th-year = 0.83). Many aspects of the small-group student centred activities were highly valued by students however, students expressed a preference for learning and interacting with teachers than colleagues. CONCLUSION: Small-group student-centred learning activities were reported as creating an active, safe learning environment with beneficial opportunities for peer-peer interaction such as questioning, teaching and learning from students. However, students expressed a preference for teacher-centred information dissemination and activities. An understanding of the rationale of student dependence to teacher-centred learning may allow improved modifications in a student-centred learning environment. PMID- 11770951 TI - Multicentricity in papillary thyroid carcinoma: analysis of predictive factors. AB - OBJECTIVES: Multicentricity has been cited as a rationale for total thyroidectomy in patients with papillary thyroid carcinoma (PTC) confined to one lobe. The purpose of this study was to examine the incidence of multicentricity of PTC in a cohort of 165 patients with PTC confined to one lobe and to examine clinical and pathologic features that may help predict for the presence of contralateral disease. DESIGN: Retrospective review. SETTING: Tertiary care hospital. METHOD: A retrospective review of 165 patients with PTC confined to one lobe treated at the Toronto General Hospital from 1992 to 1997 was performed. MAIN OUTCOME MEASURE: The predictive factors affecting the presence of multicentricity of PTC were analyzed. RESULTS: The incidence of PTC present in the contralateral lobe was 56.3%. We were unable to find any correlation of multicentricity with age, sex, tumour size, extrathyroidal spread, thyroiditis, or tall cell variant of PTC. There were trends toward higher incidence of contralateral disease in those patients with a prior history of irradiation and those with lymphatic metastases, but these trends did not reach statistical significance. CONCLUSIONS: The incidence of contralateral disease in papillary thyroid cancer treated at the Toronto Hospital was 56.3%. There was a higher incidence of contralaterality in those patients with a previous history of irradiation and in those with lymphatogenous metastases, but this did not reach statistical significance. PMID- 11770952 TI - Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy. AB - OBJECTIVE: To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. METHODS: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). RESULTS: In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. CONCLUSION: These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy. PMID- 11770953 TI - Laryngectomy clinical pathway: development and review. AB - OBJECTIVE: The goal of the study is to determine if the implementation of a protocol for the preoperative and postoperative care of patients receiving a laryngectomy for cancer of the larynx or hypopharynx (i.e., laryngectomy clinical pathway) reduced length and cost of hospital stay without increasing complication rates. DESIGN: This study is a comparison of the perioperative course of two groups of laryngectomy patients. Data were collected retrospectively from the records of patients operated on before the implementation of the clinical pathway as the institutional historical control. Comparison was made with data collected prospectively on patients operated on after the implementation of the clinical pathway. SETTING: The study was performed at a mid-sized teaching hospital associated with two regional cancer centres. All surgeries were performed by one of two otolaryngology-head and neck surgeons and residents under their supervision. METHODS: The demographic, patient, tumour, treatment, dietary, and complication data were analyzed. Fisher's exact (two-tailed) statistical test was used for parametric data and Wilcoxon scores for nonparametric data. MAIN OUTCOME MEASURE: The principal outcome measure was the length of postoperative inpatient stay. Secondary outcome measures were readmissions and postoperative complications. RESULTS: There was a statistically significant decrease of 6.7 days in the mean length of hospitalization in the clinical pathway group even when taking postoperative readmissions into account. There was no concomitant increase in surgical complications. The mean reduction in hospital cost per case was calculated to be $3,420 (Can). CONCLUSIONS: Application of a clinical pathway for patients receiving laryngectomy is both feasible and effective. PMID- 11770954 TI - Intraoperative saline and gemcitabine irrigation improves tumour control in human squamous cell carcinoma-contaminated surgical wounds. AB - INTRODUCTION AND OBJECTIVES: The cure rates for advanced head and neck cancer patients have not changed substantially in the past few decades. Most disease recurrences are local or regional and are likely due to residual microscopic disease or intraoperative wound contamination. We developed a murine model of wound implantation with microscopic disease to assess the efficiency of tumour development and used this model to evaluate the effects on tumour development of surgical bed irrigation with three different solutions. METHODS: Nonobese diabetic/severe combined immunodeficient mice were transplanted with the University of Michigan squamous cell carcinoma-22B cells derived from a human squamous cell carcinoma of the hypopharynx. Two 1-cm surgical wounds were created on the backs of 20 mice and then instilled with a known quantity of tumour cells. The minimum necessary dose to reliably result in tumour growth was then determined. Forty mice were then inoculated with this minimum tumour concentration. Ten of these mice had their incisions closed immediately and were kept as controls. Ten of the mice had their wounds irrigated with 5 cc of water and then closed, 10 had their wounds irrigated with 5 cc of saline and then closed, and 10 had their wounds irrigated with 5 cc of 1-mM gemcitabine, a nonirritating chemotherapy drug with activity in human head and neck cancers. The mice were then observed for the development of palpable tumours. RESULTS: We were unable to successfully grow tumours in any wounds that were seeded with less than 2.5 x 10(6) cells. After exposure to 2.5 x 10(6) cells, seven of eight surgical beds developed palpable tumours. This was then taken as our standard inoculation dose. All of the study mice wounds healed rapidly irrespective of irrigation solution. At postoperative day 17, 70% of the controls had evident tumour growth, whereas only 15% of the water irrigation group (p < .0005), 0% of the saline irrigation group (p < .0001), and 0% (p < .0001) of the gemcitabine irrigation group had developed tumours. By day 24, the disease recurrence rates in the water irrigation group no longer differed from controls, whereas the lower incidence of tumour recurrence in the gemcitabine and saline irrigation groups persisted. On day 56, 80% of the control mice and 75% of the water-irrigated mice group had developed palpable tumours. In the saline and gemcitabine groups, however, only 40% (p < .01) and 35% (p < .004), respectively, had evident tumours. CONCLUSIONS: In a xenograft model of tumour-cell wound contamination, irrigation with saline, water, or gemcitabine delayed tumour development. Irrigation with gemcitabine or saline improved rates of long-term disease control. Gemcitabine irrigation did not affect wound healing and was free of local complications. PMID- 11770955 TI - Congenital venous aneurysm of the internal jugular vein in a child. PMID- 11770956 TI - Endoscopic laser lithotripsy of a proximal parotid duct calculus. PMID- 11770957 TI - Teaching lesson: taking a good occupational history in unilateral nasal obstruction. PMID- 11770958 TI - Upper airway pressures in snorers and nonsnorers during wakefulness and sleep. AB - OBJECTIVE: To compare upper airway pressures in snorers and nonsnorers during sleep and wakefulness. DESIGN: Case series of snorers and nonsnoring controls. SETTING: Sleep clinic of a university hospital. METHODS: We used open catheters to measure differential nasopharyngeal and hypopharyngeal pressures in 8 nonapneic snorers with excessive daytime tiredness and 10 healthy nonsnoring controls. Measurements were performed during sleep (with the mouth taped to ensure exclusively nasal breathing) and wakefulness. When awake, the subjects were either seated (with the head neutral, flexed, extended, or rotated) or recumbent (dorsal and lateral positions). MAIN OUTCOME MEASURES: Comparison of pressures within the group as a function of body position and between the groups as a function of snoring. RESULTS: Differential nasal and pharyngeal pressures were similar in seated snorers and nonsnorers independently of head position. Assumption of recumbency resulted in significantly increased pharyngeal pressures in nonsnorers (26 +/- 18 Pa seated vs. 52 +/- 46 Pa recumbent, p < .05) and snorers (50 +/- 35 Pa seated vs. 93 +/- 38 recumbent, p < .01). The increase was higher in snorers than nonsnorers. During snoring, sleep differential pharyngeal pressures in snorers were markedly increased compared to quiet sleep (567 +/- 450 Pa during snoring epochs vs. 117 +/- 82 Pa during nonsnoring epochs, p < .01). CONCLUSIONS: Compared to nonsnorers, recumbent nonapneic snorers have elevated differential pharyngeal pressures indicative of increased upper airway resistance and reduced airway patency; this is present during wakefulness and sleep. PMID- 11770959 TI - Ambulatory adenotonsillectomy in children less than 5 years of age. AB - OBJECTIVE: Post-tonsillectomy monitoring has received a significant amount of attention in recent years. Although the literature questions the safety of ambulatory adenotonsillectomy in children less than 5 years of age, age alone did not exclude eligibility for day surgery at our institution. METHOD: A retrospective chart review was performed between 1995 and 1998 for all children who had undergone adenoidectomy or adenotonsillectomy at the London Health Sciences Centre in London, ON. RESULTS: There were 119 adenoidectomies and 278 adenotonsillectomies performed. The average age was 3 years at the time of surgery. One hundred and ninety-six cases were performed for obstruction, and 201 were done for infection. Average time spent in the postanaesthesia care unit was 6 hours for adenotonsillectomy and 4.5 hours for adenoidectomy. There were 26 planned and 60 unplanned admissions. One (4/397) percent of the unplanned admissions were for postoperative hemorrhage; 14% (56/397) were for vomiting and dehydration. No cases were admitted for postoperative desaturations or hypotensive episodes. The readmission rate was 0%. CONCLUSIONS: Ambulatory adenotonsillectomy is a safe procedure in children less than 5 years old. However, a well-informed, reliable caretaker and support from the day surgery staff is essential in early discharge of young patients after adenotonsillectomy. PMID- 11770960 TI - Cytologic evaluation of surgical irrigation fluid following resection of head and neck squamous cell carcinoma. AB - INTRODUCTION: Historically, squamous cells exfoliated from head and neck carcinoma resection have been implicated in locoregional recurrence, but there have been few studies demonstrating the presence of these cells. This study was designed to evaluate the presence of exfoliated malignant cells in surgical irrigation fluid collected during head and neck cancer resection. METHODS: Thirty patients undergoing surgery for biopsy-proven squamous cell carcinoma had their surgical sites irrigated with 1,000 cc of normal saline. Surgical gloves and instruments were also washed. These samples were prepared and stained using standard squamous cell cytologic stains. All cases were reviewed by one cytopathologist. RESULTS: Eighteen patients (60%) had positive or suspicious cytology detected in at least one of the surgical samples. In patients with T0 and T1 tumours, all surgical samples were negative. Positive or suspicious cytology was detected in the primary site and glove and instrument irrigation in 40% of patients with T2 tumours, 42% of patients with T3 tumours, and 50% of patients with T4 tumours. This was statistically significant (p < .05). Positive or suspicious cytology was detected in the neck and glove and instrument irrigation in 29% of patients with an N0 neck, 31% of patients with an N1 neck, 39% of patients with an N2 neck, and 100% of patients with an N3 neck. Five of seven patients (71%) with previous radiation therapy had positive or suspicious cytology in at least one of the surgical samples. CONCLUSIONS: Higher tumour and nodal staging and a previous history of radiation therapy are associated with an increased incidence of positive or suspicious cytology in surgical irrigation fluid. These findings have implications for surgical protocols. PMID- 11770961 TI - Accuracy and usefulness of radiographic assessment of cervical neck infections in children. AB - OBJECTIVE: To determine the accuracy and usefulness of computed tomography (CT) in diagnosis and management of lateral and deep neck infections METHODS: An 11 year retrospective review of 110 children (age range 1 months to 17 years) was conducted at a tertiary care children's hospital. RESULTS: Fifteen patients treated medically (8 with cellulitis, 7 with early abscess) improved. Of the remaining 95 patients who had 107 cervical sites drained surgically, CT predicted accurately operative findings in 81 (76%) cases (72 with abscess, 9 with cellulitis). In the 26 (24%) cases with discrepancy between CT interpretation and operative findings, the most common problem was differentiating early abscess from cellulitis with 18 false positives (no abscess at surgery). In 8 cases, CT diagnosis other than abscess was made (4 cellulitis, 1 inflammatory mass, 1 hematoma, 1 lymphangioma, and 1 tumour); however, when the patients were operated on because of lack of improvement, an abscess was found. CONCLUSIONS: Although CT is helpful both in determining the presence and location of neck infections in children, the CT scan is less helpful in differentiating abscess from lymphadenitis, cellulitis, and some complex cervical masses. PMID- 11770962 TI - Hyperacusis in Williams syndrome. AB - OBJECTIVE: To define hyperacusis in audiologic parameters and to further elucidate central and peripheral auditory pathways. DESIGN AND SETTING: Theories surrounding hyperacusis have always been highly debated. A group of children with Williams syndrome universally complain of hyperacusis. They have highly reproducible behavioural responses to noise and are thus hampered in their social interactions. Loss of inhibitory modulation to efferent sensory input to the cochlea is thought to be a possible mechanism. METHODS: Nine patients with Williams syndrome received a complete audiologic work-up, including audiogram, speech reception thresholds, acoustic reflexes, impedance, and transient evoked otoacoustic emissions (TEOAEs). MAIN OUTCOME MEASURES: Assessment of the efferent system is done by measuring changes in TEOAEs following stimulation of the contralateral ear. RESULTS: Three patients had high-frequency sensorineural hearing loss (SNHL) and thus, as expected, absent TEOAEs, indicating cochlear damage. Two had normal hearing and normal TEOAEs. However, four patients had normal hearing with absent TEOAEs. CONCLUSIONS: These findings are suggestive of cochlear disease and may, in fact, support the hypothesis of outer hair cell modulation by the ipsilateral medial olivocochlear system. Behavioural aspects of the syndrome make audiologic testing difficult. Thus, the diagnosis of SNHL may be hampered if it truly exists. The data show a preponderance of SNHL in the older age groups of our study population. This either reflects previously missed diagnoses or underlying cochlear disease, which may manifest later in life. Thus, this finding blurs the boundary between loudness recruitment and hyperacusis. PMID- 11770963 TI - Impact of rhinosinusitis in health care delivery: the Quebec experience. AB - OBJECTIVE: Rhinosinusitis is a common disease affecting 135 per 1,000 population. The cost and the impact on quality of life of this disease are considerable. Health care delivery for a particular disease is evaluated through the health impact of the disease, outcomes of treatments, and their costs. This article reviews our experience with rhinosinusitis and its impact on health, as measured using a generic quality of life instrument, the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36), in a selected patient population. Outcomes of treatments will be introduced, and the economic impact of chronic rhinosinusitis based on a U.S. study will be discussed. MATERIAL AND METHODS: One hundred and ten patients (divided into three subgroups: recurrent acute rhinosinusitis, chronic rhinosinusitis, and nasal polyposis) completed the SF-36 survey on the day of the diagnostic visit in the outpatient sinus clinics of two hospitals. RESULTS: The scores of the SF-36, in chronic rhinosinusitis, are compared with the normative values of a healthy U.S. population showing statistically significant differences in seven of eight domains. A comparison of the scores of chronic rhinosinusitis with a U.S. study on chronic rhinosinusitis shows statistically significant differences in five of eight domains. A comparison of the scores in the three diagnostic subgroups shows a statistical significance in two domains: bodily pain and vitality are more affected in recurrent acute and chronic rhinosinusitis. CONCLUSIONS: Chronic rhinosinusitis affects the quality of life of patients with rhinosinusitis and represents an important health burden. Some differences are noted with the U.S. chronic rhinosinusitis population. Recurrent acute and chronic rhinosinusitis seem to have more impact on vitality and bodily pain than nasal polyposis. PMID- 11770964 TI - Role of the sternocleidomastoid muscle flap preventing Frey's syndrome and maintaining facial contour following superficial parotidectomy. AB - The sternocleidomastoid muscle flap may play a significant role in reducing the incidence of Frey's syndrome and maintaining facial contour after parotidectomy. Patients who underwent superficial parotidectomy from August 1992 to March 1999 were divided into two groups (N = 26). One group had sternocleidomastoid muscle flap reconstruction. A historical cohort study was designed with the two groups being matched for sex, age, pathology, postoperative radiation, date of surgery, and extent of dissection. The starch iodine test was used to evaluate for gustatory sweating, and the Observer Rated Disfigurement Scale was used to assess facial contour and aesthetics. The results of our study suggest that the sternocleidomastoid flap reconstruction following parotidectomy surgery does not alter the incidence of Frey's syndrome and does not significantly improve facial contour and aesthetics. PMID- 11770965 TI - Mitomycin C in sinus surgery: preliminary results in a rabbit model. AB - Mitomycin C (MMC) is an antineoplastic agent with an antiproliferative effect on fibroblasts. It is routinely used topically in ophthalmology. The goal of this research project is to evaluate if topically applied MMC at the site of a maxillary antrostomy will inhibit the healing process of the mucosa and reduce the risk of postoperative stenosis. Antrostomies were carried out in both maxillary sinuses of 10 rabbits. For each rabbit, MMC is applied at the site of the antrostomy on one side while the other side serves as control. Antrostomies are re-evaluated 3 weeks later and their areas measured precisely. Seven of 10 control antrostomies were closed compared to only 1 of the 10 treated with MMC (p = .014). Comparison of the areas of the control and treated sides also proved to be statistically significant (p = .0039). Topical application of MMC was not associated with any systemic side effects and did not cause any permanent microscopic changes since the mucosa re-epithelialized normally. These results suggest that MMC slows the postoperative healing process of the nasal mucosa of the rabbit without affecting re-epithelialization. This could allow antrostomies to heal with a wider diameter, decreasing the risk of postoperative stenosis. Our next step will be to reproduce these results following functional endoscopic surgery on humans. PMID- 11770966 TI - Comparison of postoperative pain: tonsillectomy by blunt dissection or electrocautery dissection. AB - PURPOSE: To compare post-operative pain in children undergoing tonsillectomy by blunt dissection or electrocautery. METHOD: Thirty-six children between the ages of 5 and 15 years were recruited for the study. Tonsillectomy was done in a standardized fashion with uniform anaesthetic practices. Each child kept a pain diary for 10 days, recording pain twice daily on a Visual Analog Scale and Faces Pain Scale. Doses of analgesics were recorded. RESULTS: There were no statistically significant differences in the pain scores for the groups, although there was a trend toward more pain in the blunt dissection group. There were more complications in this group, and these children used significantly more doses of acetaminophen. Sources of bias are discussed. CONCLUSION: These results suggest a trend toward greater postoperative pain in children who have tonsillectomies by blunt dissection techniques. PMID- 11770967 TI - Functional endoscopic sinus surgery in the paediatric population: outcome of a conservative approach to postoperative care. AB - Functional endoscopic sinus surgery (FESS) has become a widely used and effective tool in treating chronic sinusitis refractory to medical therapy. Reported success rates, defined mainly on the basis of improvement of preoperative symptoms, have been encouraging and ranged between 71 and 93%. However, in most of these studies, a second-look endoscopy under general anaesthesia was performed 2 to 3 weeks following the initial surgery in order to debride and clean the operative site. In this study, we present the outcome of FESS in our centre, where a second-look endoscopy was never performed. A retrospective study on all of the patients operated on between May 1987 and May 1997 was undertaken. All 35 patients had symptoms of sinusitis and had received initial medical therapy for at least 2 months. Only those who did not improve were considered candidates for surgery. Prior to the operation, all patients had computed tomography scan of the sinuses to document the extent of their disease. Eleven patients (31%) had asthma, 3 patients had cystic fibrosis, 1 had leukemia, 1 had immotile cilia, and 1 had Kartagener's syndrome. The period of follow-up ranged between 3 months and 5 years. Success was determined by resolution or improvement of the preoperative symptoms as assessed during their latest follow-up visit. Our data show an overall success rate of 74%. More than half of the patients (56%) who had recurrence of symptoms had an underlying systemic condition (cystic fibrosis, leukemia, or ciliary dyskinesia); however, these patients showed an initial improvement during the first few months following FESS. Also, five patients (14%) required revision FESS within 1 to 3 years following their initial surgery; four of those patients (80%) had an underlying systemic condition. Based on these results, we conclude that second-look endoscopy is of no benefit following routine FESS since our success rates are comparable to those reported in the literature. PMID- 11770968 TI - Carbon dioxide laser microsurgery for tongue cancer: surgical techniques and long term results. AB - Thirty-seven consecutive patients with cancer of the anterior two-thirds of the tongue without clinical neck lymph nodes or distant metastasis were treated with transoral carbon dioxide (CO2) laser microsurgery. During the operation, a monopolar coagulation-suction device was applied to achieve a clear surgical field. Under a surgical microscope, we repeatedly palpated the soft tissue to identify the tumour margins, in particular the deep margin, to maintain adequate safe margins in three dimensions. We resected the tumour by en bloc procedures rather than by vaporization or debulking. Of the 28 patients in the T1 and T2 groups, 26 patients did not receive postoperative radiotherapy. The local control rate calculated by the methods of Kaplan and Meier in all 37 patients at 5 years was 93.6%. No local recurrence occurred in the T1 or T2 cases. Nine patients suffered from neck recurrence and the neck control rate at 5 years was 74.6%. Eight of these nine patients were salvaged by surgery with adjuvant radiotherapy, and six of them finally achieved disease-free status. The 5-year disease-free survival rate for our series was 88%. Our surgical techniques using CO2 laser microsurgery are effective and advantageous methods for excision of oral tongue cancer, especially stage I and II lesions. PMID- 11770969 TI - Clinical manifestations of sinonasal pathology during pregnancy. AB - OBJECTIVE: Pregnancy may confer a number of conditions related to the head and neck. The objective of this study was to evaluate the clinical manifestations of sinonasal pathology that occur during pregnancy. METHODS: Thirty-three pregnant patients were evaluated for the occurrence of rhinorrhea, congestion, epistaxis, or acute sinusitis during the first trimester of pregnancy, controlling with 28 women of child-bearing age. A visual analogue scale was used to grade the severity of each symptom. Statistical analysis was carried out to assess for significant differences in the prevalence and severity of symptomatology between cases and controls. RESULTS: Compared to the control group, there was no statistically significant difference in the prevalence of congestion, epistaxis, rhinorrhea, or acute sinusitis. There was no statistically significant difference in the severity of any presenting symptom between pregnant and control group patients. CONCLUSION: Pregnancy is not associated with an increased prevalence or severity of nasal symptomatology during early pregnancy. The influence of hormonal changes on nasal physiology during pregnancy is discussed with a view toward safe management. PMID- 11770970 TI - Anterior and posterior middle ear congenital cholesteatomas in children. AB - Congenital cholesteatomas arise from embryonic epithelial cell rests in the middle ear cleft. We report our series of 19 cases observed in 18 children between 1985 and 1990. Clinical data and surgical observations are analyzed. In regard to the location of the lesions, our findings are consistent with most of what has been reported in the literature. Sixty-eight percent of the lesions originated from the anterosuperior part of the mesotympanum. Only 10% were posterosuperiorly located. Pathogenic mechanisms are discussed with respect to the lesion's primary site. PMID- 11770971 TI - Pectoralis major myocutaneous pedicled flap in head and neck reconstruction: retrospective review of indications and results in 244 consecutive cases at the Toronto General Hospital. AB - The pectoralis major myocutaneous pedicled flap (PMMPF) has been considered to be the "workhorse" of pedicled flaps for head and neck reconstruction, and several series of PMMPF procedures have been reported in the literature. Between 1983 and 1997, 244 reconstruction procedures using the PMMPF were carried out on 229 patients by the Otolaryngology-Head and Neck Surgery Department at the Toronto General Hospital. Pectoralis major myocutaneous pedicled flap reconstructions were completed after ablation of cancer in the following sites: oral cavity, 113; oropharynx/hypopharynx, 50; larynx, 59; and other, 21. The locations of reconstruction were oral cavity, 121; pharynx, 74; and neck or face, 50. Of the 244 cases, 202 were carried out as primary reconstructive procedures, whereas 42 flaps were "salvage" procedures (reconstruction after fistula, flap failure, osteoradionecrosis, and internal jugular vein rupture). Eighty-five cases (35%) were affected by complications such as dehiscence, infection, hematoma, seroma, partial flap failure, total flap failure, fistula, and donor site complications. The duration of admission for cases with complications was longer, and higher complication rates were associated with salvage procedures, number of comorbidities, number of pack-years of cigarettes smoked, and oral cavity reconstructions. This series of consecutive PMMPF procedures is the largest reported to date. PMID- 11770972 TI - Endoscopic thyroidectomy. PMID- 11770973 TI - Mucocele of the crista galli. PMID- 11770974 TI - Auditory neuropathy: when test results conflict. PMID- 11770975 TI - Nasofrontal schwannoma with intracranial extension. PMID- 11770976 TI - Pediatric laryngeal cancer: case report and review of literature. PMID- 11770977 TI - Epiglottic carcinoma presenting as obstructive sleep apnea. PMID- 11770979 TI - Stereotactic computer-assisted navigational sinus surgery: historical perspective and review of the available systems. PMID- 11770978 TI - Supraglottic tumour categories: 1987 and 1997 International Union Against Cancer classification. AB - PURPOSE: To verify the correlation to survival of 1987 and 1997 Union Internationale Contre le Cancer (UICC; International Union Against Cancer) supraglottic tumour categories. MATERIALS AND METHODS: Two hundred and sixty patients seen at the ENT Clinic at the University of Ferrara from 1970 to 1990 had a complete follow-up and met the criteria of enrolment in this study. Data were analyzed by means of survival analyses (Kaplan-Meier and Cox algorithms). RESULTS: Multivariate analysis (adjusted for number and patient's age) of 1997 UICC supraglottic tumour categories (T1 vs. T4) showed a significant correlation with the survival rate, whereas 1987 UICC categories did not reach any significant statistical value. CONCLUSION: The 1997 UICC tumour categories represent an improvement in supraglottic cancer classification. PMID- 11770980 TI - N-acetylcysteine for cholesteatoma? PMID- 11770981 TI - Immunological reagents: catalysts for research progress. PMID- 11770982 TI - A new modified live equine influenza virus vaccine: phenotypic stability, restricted spread and efficacy against heterologous virus challenge. AB - Flu Avert IN vaccine is a new, live attenuated virus vaccine for equine influenza. We tested this vaccine in vivo to ascertain 1) its safety and stability when subjected to serial horse to horse passage, 2) whether it spread spontaneously from horse to horse and 3) its ability to protect against heterologous equine influenza challenge viruses of epidemiological relevance. For the stability study, the vaccine was administered to 5 ponies. Nasal swabs were collected and pooled fluids administered directly to 4 successive groups of naive ponies by intranasal inoculation. Viruses isolated from the last group retained the vaccine's full attenuation phenotype, with no reversion to the wild-type virus phenotype or production of clinical influenza disease. The vaccine virus spread spontaneously to only 1 of 13 nonvaccinated horses/ponies when these were comingled with 39 vaccinates in the same field. For the heterologous protection study, a challenge model system was utilised in which vaccinated or naive control horses and ponies were exposed to the challenge virus by inhalation of virus containing aerosols. Challenge viruses included influenza A/equine-2/Kentucky/98, a recent representative of the 'American' lineage of equine-2 influenza viruses; and A/equine-2/Saskatoon/90, representative of the 'Eurasian' lineage. Clinical signs among challenged animals were recorded daily using a standardised scoring protocol. With both challenge viruses, control animals reliably contracted clinical signs of influenza, whereas vaccinated animals were reliably protected from clinical disease. These results demonstrate that Flu Avert IN vaccine is safe and phenotypically stable, has low spontaneous transmissibility and is effective in protecting horses against challenge viruses representative of those in circulation worldwide. PMID- 11770983 TI - Efficacy of a cold-adapted, intranasal, equine influenza vaccine: challenge trials. AB - A randomised, controlled, double-blind, influenza virus, aerosol challenge of horses was undertaken to determine the efficacy of a cold-adapted, temperature sensitive, modified-live virus, intranasal, equine influenza vaccine. Ninety 11 month-old influenza-naive foals were assigned randomly to 3 groups (20 vaccinates and 10 controls per group) and challenged 5 weeks, 6 and 12 months after a single vaccination. Challenges were performed on Day 0 in a plastic-lined chamber. Between Days 1 and 10, animals were examined daily for evidence of clinical signs of influenza. Nasal swabs for virus isolation were obtained on Day 1 and Days 1 to 8 and blood samples for serology were collected on Days 1, 7 and 14. There was no adverse response to vaccination in any animal. Following challenge at 5 weeks and 6 months, vaccinates had significantly lower clinical scores (P = 0.0001 and 0.005, respectively), experienced smaller increases in rectal temperature (P = 0.0008 and 0.0007, respectively) and shed less virus (P<0.0001 and P = 0.03, respectively) over fewer days (P<0.0001 and P = 0.002, respectively) than did the controls. After the 12 month challenge, rectal temperatures (P = 0.006) as well as the duration (P = 0.03) and concentration of virus shed (P = 0.04) were significantly reduced among vaccinated animals. The results of this study showed that 6 months after a single dose of vaccine the duration and severity of clinical signs were markedly reduced amongst vaccinated animals exposed to a severe live-virus challenge. Appropriate use of this vaccine should lead to a marked reduction in the frequency, severity and duration of outbreaks of equine influenza in North America. PMID- 11770984 TI - Passive transfer of maternal immunoglobulin isotype antibodies against tetanus and influenza and their effect on the response of foals to vaccination. AB - Influenza and tetanus-specific antibodies of the IgG sub-isotypes are posively transferred to foals via colostrum and inhibit their response to inactivated influenza vaccines and tetanus toxoid. High titres of influenza antibodies of IgGa and IgGb subisotypes and tetanus antibodies of the IgGa, IgGb and IgG(T) subisotypes were detected in postsucking serum samples collected from foals born to mares that had received booster doses of multicomponent vaccines during the last 2 months of gestation. Thereafter, titres declined in an exponential manner but were still detectable in all foals at age 26 weeks, regardless of whether they had been vaccinated prior to age 26 weeks. Mean +/- s.e. half-life of decline of influenza IgGa antibodies (27.0 +/- 2.3 days) was significantly shorter than that of influenza IgGb antibodies (39.1 +/- 2.7 days; P<0.005). Tetanus IgGa and IgGb antibodies declined with half-lives of 28.8 +/- 3.0 and 34.8 +/- 5.1 days, respectively. Titres of tetanus IgG(T) antibodies were substantially higher than those of influenza IgG(T) antibodies in postsucking samples and remained so through age 26 weeks, declining with a half-life of approximately 35 days. Postsucking titres of tetanus and influenza antibodies of the IgA isotype were low and declined rapidly to undetectable levels. Yearlings showed significant increases in titre of influenza IgGa, IgGb and IgG(T) subisotype antibodies but no increase in influenza IgA antibodies in response to 2 doses of multicomponent vaccines containing tetanus toxoid and inactivated influenza A-1 and A-2 antigens. Yearlings also showed strong tetanus IgGa, IgGb and IgG(T) subisotype responses to one dose of vaccine and a substantial further rise in titre in response to administration of a second dose 3 weeks later, but failed to show an increase in titre of tetanus IgA antibodies. The influenza and tetanus IgGa, IgGb and IgG(T) subisotype responses of 6-month-old foals to vaccination followed the same pattern as those shown by yearlings but titres were generally lower. In contrast, 3-month-old foals failed to show increases in titre of either influenza or tetanus IgG subisotypes in response to 2 doses of vaccine and generally needed 1-3 additional booster doses of vaccine to achieve titres similar to those achieved by yearlings after 2 doses. Based on the finding that maternal antibodies exert a significant inhibitory effect on the response of foals to tetanus toxoid and inactivated influenza antigens, it is recommended that primary immunisation of foals born to vaccinated mares should not commence before age 6 months. PMID- 11770985 TI - The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens. AB - Equine herpesvirus-1 (EHV-1) remains a frequent cause of upper respiratory tract infection and abortion in horses worldwide. However, little is known about the local antibody response elicited in the upper airways of horses following exposure to EHV-1. This study analysed the mucosal humoral immune response of weanling foals following experimental infection with virulent EHV-1, or vaccination with either of 2 commercial vaccines. Twenty weanlings were assigned to 5 groups and were inoculated with, or vaccinated against, EHV-1 following different regimens. Finally, all weanlings were simultaneously challenged intranasally with virulent EHV-1 Army 183 (A183). Nasal wash and serum samples were collected at regular intervals until 13 weeks after final challenge. Nasal washes were assayed for EHV-1-specific equine IgGa, IgGb, IgG(T), IgA, IgM and total virus-specific antibody using an indirect, quantitative ELISA. Total serum antibody responses were also monitored, and clinical signs of EHV-disease were recorded for each individual. Virus-specific IgA dominated the mucosal antibody response elicited in weanlings inoculated with A183, being detectable at up to 3.1 microg/mg total IgA 13 weeks after challenge. Neither inactivated EHV-1 administered i.m., nor attenuated EHV-1 administered intranasally induced detectable mucosal antibodies. EHV-1-specific mucosal antibodies impeded EHV-1 plaque formation in vitro. Such virus-neutralising antibody probably contributes to a reduction of shedding of EHV-1 from the respiratory tract of virus-infected horses. PMID- 11770986 TI - Altered immune responses to a heterologous protein in ponies with heavy gastrointestinal parasite burdens. AB - This study was performed to test the hypothesis that immunity to heterologous vaccination would improve when the parasites were removed. It was also expected that parasitised ponies would exhibit a biased Th2 cytokine response to KLH immunisation. Helminth parasites are common in horses even in the era of highly effective broad-spectrum antiparasiticides. These parasites have been shown to alter the outcome to heterologous immunisation in a number of host species. The effect of gastrointestinal parasites on heterologous vaccination has not been addressed in equids. In the current study, humoral, lymphoproliferative, and cytokine responses to a single i.m. injection of keyhole limpet haemocyanin (KLH) were compared between groups of ponies with high, medium or low gastrointestinal parasite burdens. Antibody levels determined by ELISA showed that animals with low levels of parasites had a trend toward increased KLH specific total immunoglobulin, IgG(T) and IgA compared to heavily parasitised ponies. Medium and heavily parasitised ponies demonstrated a trend toward reduced lymphoproliferative response to KLH that was not restored after the addition of interleukin-2 (Il-2). Cells from these ponies also produced significantly lower levels of IL-4 compared to lightly parasitised ponies. These data indicate that heavily parasitised ponies have uniformly decreased cellular and humoral immune responses to soluble protein immunisation. The mechanisms involved may have potential deleterious effects on standard vaccine protocols of parasitised equines. PMID- 11770987 TI - Exercise alters the immune response to equine influenza virus and increases susceptibility to infection. AB - Equine influenza virus remains a major health concern for the equine industry in spite of ongoing vaccination programmes. Previous work has shown that the immune system of horses can be affected by strenuous exercise. The possible adverse consequence of exercise-induced alterations in lymphocyte responses measured in vitro was unknown. Here we demonstrate that subjecting vaccinated ponies to a 5 day strenuous exercise programme results in a significant suppression of their T cell-mediated immune response to equine influenza virus as measured by decreased lymphoproliferation and gamma interferon production measured in vitro. These same ponies also demonstrated increased susceptibility to influenza disease following a challenge exposure to the same strain of virus. Rested ponies that had received the same vaccine and challenge were completely protected from disease. Our results demonstrate that exercise-induced suppression of the equine immune response to influenza virus can be associated with an increased susceptibility to disease. PMID- 11770988 TI - Opsonic capacity of foal serum for the two neonatal pathogens Escherichia coli and Actinobacillus equuli. AB - Two of the most commonly isolated foal pathogens are Escherichia coli and Actinobacillus equuli. The hypothesis tested in this study was that young foals carry a lower opsonic capacity for these bacteria compared to adult horses. A flow-cytometric method for the phagocytosis of these by equine neutrophils was established. The opsonic capacity of serum from healthy foals from birth to age 6 weeks was evaluated and related to the concentrations of IgGa and IgGb. Phagocytosis of yeast was used as a control. Serum was required for phagocytosis, with higher concentrations for E. coli than for A. equuli. Ingestion of colostrum led to a significantly higher serum opsonic capacity. After that, there was no consistent age-related trend for opsonic capacity for the different microbes. Foal serum showed similar or higher opsonisation of E. coli and A. equuli compared to serum from mature individuals. During the studied period, the predominance among IgG subisotypes switched from IgGb to IgGa. Although the overall correlation between concentrations of IgG subisotypes and serum opsonic capacity was poor, sera with IgGb levels below 1.9 mg/ml induced lower opsonisation of E. coli and yeast, but not of A. equuli. Complement activation was important for opsonisation of all tested microbes. The results of this study are significant to the understanding of a key immunological facet in the pathophysiology of equine neonatal septicaemia in clinical practice. PMID- 11770989 TI - Neutrophil functions and serum IgG in growing foals. AB - The aim of this study was to investigate the phagocytic and killing capacities as well as expression of CD18 of neutrophils obtained from healthy foals from birth to age 8 months. Blood was taken from 6 Standardbred foals at 7 time-points between ages 2-56 days and thereafter once a month. For comparison, cells from 16 mature horses were evaluated. Neutrophil phagocytosis of yeast cells was assessed by flow cytometry after opsonisation with mature pooled serum, autologous serum or anti-yeast IgG. The killing capacity of the neutrophils, as indicated by the oxidative burst, was monitored by chemiluminescence. Serum IgG concentration was measured by radial immunodiffusion. In addition to clinical examination, the amount of serum amyloid A and the total leucocyte count were used as markers for infection. The phagocytic ability was impaired until age 3 weeks, when autologous serum was used as opsonin. Killing capacity was also low initially but, from 3 months onwards, chemiluminescence values were equal to or higher than in mature horses. Serum IgG decreased from 10 g/l at 2 days to 5 g/l at 2 months and then increased gradually to 10 g/l at the end of the study. These findings may in part explain the increased susceptibility to bacterial infections in young horses. PMID- 11770990 TI - Evaluation of IgG concentration and IgG subisotypes in foals with complete or partial failure of passive transfer after administration of intravenous serum or plasma. AB - The purpose of this study was to evaluate the ability of an equine plasma product i.v. and a concentrated serum product i.v. to deliver antibodies to 46 foals with failure of passive transfer (FPT). Treatment of FPT was as per manufacturers recommendations, using plasma (950 ml/unit) or a concentrated serum product (250 ml/unit). Significant variables affecting the 3 day post-transfusion serum immunoglobulin G (IgG) concentration of foals included body weight, pretransfusion IgG concentration, number of product units transfused, foaling season and product administered. Plasma treatment had a greater increase in post transfusion serum IgG concentrations compared to the serum product treatment mainly because plasma contained approximately twice the amount of IgG per unit as the serum product. The change in equine influenza virus and tetanus toxoid specific IgGa, IgGb, and IgG(T) titres was measured in foals from pretransfusion to 3 days post-transfusion. For each gram of IgG transfused, the change in antigen-specific IgG subisotypes were similar for both treatment groups. The results of this study suggest that similar foal serum IgG concentrations can be achieved 3 days post-transfusion by administering 1 unit of plasma or 2-3 units of serum product. PMID- 11770991 TI - An immunodeficiency in Fell ponies: a preliminary study into cellular responses. AB - A putative immunodeficiency, causing mortality in UK Fell pony foals (Fell pony syndrome), was studied in affected foals and compared with healthy, age-matched foals. Differential cell counts of peripheral blood indicated that the syndrome foals were lymphopenic (P<0.05). Flow cytometric analysis of circulating leucocytes showed a reduced MHC II expression (P<0.01) on lymphocytes but not on polymorphonuclear cells in affected foals. There were no changes in the percentages of CD4+ or CD8+ T cells. There was an increased (P<0.05) expression of CD11a/18 by the lymphocytes of the syndrome foals, compared to the control foals, which is probably a response to systemic bacterial infections. The syndrome foals' lymphocytes responded to mitogens (PHA, ConA, PWM) at normal levels. The data do not conform to any known immunodeficiencies identified in any other species. Further analyses will be required, particularly on bone marrow function. PMID- 11770992 TI - Production of biologically active equine interleukin 12 through expression of p35, p40 and single chain IL-12 in mammalian and baculovirus expression systems. AB - Interleukin-12 (IL-12) is a key cytokine in the development of cell-mediated immune responses. Bioactive IL-12 is a heterodimeric cytokine composed of disulphide linked p35 and p40 subunits. The aim of this study was to verify biologically activity of the products expressed from equine interleukin-12 (IL 12) p35 and p40 cDNAs and to establish whether equine IL-12 could be expressed as a p35/p40 fusion polypeptide, as has been reported for IL-12a of several mammalian species. We report production of equine IL-12 through expression of p35 and p40 subunits in mammalian and insect cells and of a p35:p40 fusion polypeptide in mammalian cells. Conditioned medium recovered from cultures transiently transfected with constructs encoding equine p35 and p40 subunits or single chain IL-12 enhanced IFN-gamma production in cells derived from equine lymph nodes. Preincubation of IFN-gamma inducing preparations with anti-p40 monoclonal antibody resulted in a significant decrease in IFN-gamma induction capacity. Medium recovered from p35 and p40-expressing baculovirus infected cultures enhanced target cell IFN-gamma production and proliferation. Experimental studies in mice and other animals have revealed a therapeutic benefit of IL-12 in cancer, inflammatory and infectious disease and an adjuvant effect in prophylactic regimes. Production of a bioactive species-specific IL-12 is a first step towards an investigation of its potential application in equine species. PMID- 11770994 TI - Detection of IgG and IgE serum antibodies to Culicoides salivary gland antigens in horses with insect dermal hypersensitivity (sweet itch). AB - We postulated that all horses exposed to the bites of Culcoides (midges) would have an antibody response to the antigen secreted in Culcoides saliva, but that IgE antibody would be restricted to allergic individuals. Using immunohistology on sections of fixed Culicoides, we have demonstrated the presence of antibodies in horse serum which recognise Culicoides salivary glands. Antibodies were detected in the serum of horses with insect dermal hypersensitivity and in the serum of normal horses exposed to Culicoides bites. In contrast, no antibodies were detected in serum from native Icelandic ponies which had not been exposed to Culicoides. Anti-salivary gland IgG antibodies were detected in serum from both allergic and healthy horses exposed to Culicoides. IgE antibodies were only detected in horses with signs of insect dermal hypersensitivity, they were not found in serum of healthy controls nor in the serum of horses with a history of hypersensitivity but in remission at the time of sampling. Using western blotting we confirmed the presence of antibodies to Culicoides antigens and demonstrated that individual horses react to different numbers of antigens. This paper demonstrates the ability of serum from allergic horses to detect Culcoides antigens and will enable further studies to isolate and characterise the allergens. PMID- 11770993 TI - Immunoglobulin-E-bearing cells in skin biopsies of horses with insect bite hypersensitivity. AB - The aim of the present study was to investigate, with immunohistochemistry and in situ hybridisation, if immunoglobulin-E (IgE) and mast cells are involved in the pathogenesis of insect bite hypersensitivity (IBH), an allergic dermatitis of horses. In tissue sections fixed in paraformaldehyde (PFA) for <24 h, significantly more IgE protein-bearing cells were found in the dermis and epidermis of acute and chronic IBH lesions than in skin biopsies from healthy horses (medians = 466, 236 and 110 cells/mm2, respectively; P < or = 0.01). More IgE-mRNA positive (+) cells were observed in the dermis of acute IBH lesions than in the dermis of healthy skin (median = 2.8 vs. 0.0 cells/mm2; P < or = 0.01). Significantly, more mast cells were detected with metachromatic (median = 160 vs. 62 cells/mm2; P < or = 0.001) and tryptase-specific stainings (median = 120 vs. 69 cells/mm2; P < or = 0.001) in the dermis of acute IBH biopsies compared to healthy skin. No chymase+ mast cells were found in any skin biopsy. IBH lesions fixed in PFA for >24 h were compared to dermatomycosis (DM) lesions; IBH biopsies contained a similar number of IgE-protein+ cells to DM biopsies (median = 249 vs. 192 cells/mm2; P = 0.08) but had significantly more IgE-mRNA+, metachromatic and tryptase+ mast cells than DM biopsies. This study suggests an involvement of IgE mediated immune reactions in the pathogenesis of IBH as well as, sometimes, in dermatomycosis. Using double labelling, cells which expressed IgE protein and contained mast cell enzymes were detected. PMID- 11770995 TI - Influence of environmental and genetic factors on allergen-specific immunoglobulin-E levels in sera from Lipizzan horses. AB - To investigate whether allergen-specific IgE production is influenced by environmental and genetic factors, IgE levels against 2 mould extracts (Alternaria alternata [Alt a] and Aspergillus fumigatus [Asp f]) and against recombinant (r) rAlt a 1, rAsp f 7 and rAsp f 8 were determined by ELISA in sera from 448 Lipizzan horses living in 6 studfarms. Statistical evaluation showed a significant effect of studfarm-specific environment on IgE levels against the different allergens, but genetic factors also influenced allergen-specific IgE production: an heritability of 0.33 was found for IgE levels against the 2 mould extracts and of 0.21 for rAsp f 8-specific IgE. Heritability estimates for rAlt a 1- and rAsp f 7-specific IgE were negligible. Investigations for a possible association between Major Histocompatibility Complex (MHC) class I antigens and specific IgE levels were carried out. The most consistent significant association was found between the equine leucocyte antigen (ELA) A8 and undetectable IgE titres against rAsp f 7 and rAsp f 8. Significant ELA associations were also demonstrated between ELA A1 and higher specific IgE levels, between ELA A14 and lower IgE levels against the mould extracts and in one studfarm between ELA Be27 and lower Aspergillus-specific IgE levels. PMID- 11770996 TI - Transforming growth factor beta concentrations and interferon gamma responses in cerebrospinal fluid of horses with equine protozoal myeloencephalitis. AB - The following experiment was performed to test the hypothesis that transforming growth factor beta (TGF-beta) concentration varies in the cerebrospinal fluid and serum of horses with EPM and to determine if cerebrospinal fluid (CSF) alters the interferon-gamma (IFN-gamma) rersponse of equine peripheral blood mononuclear cells (PBMCs). The concentration of transforming growth factor-beta (TGF-beta2) was investigated in the serum and cerebrospinal fluid (CSF) of 18 horses (9 normal, 9 affected with equine protozoal myeloencephalitis [EPM]). The TGF-beta2 assay was validated in a group of 6 normal horses. Intra-assay variability was 4.7%, and interassay variability was 10.7%. The slope of the curve of the unknown samples of various volumes demonstrated parallelism with a curve developed using equal volumes of assay kit standard. Assay of normal and EPM-affected horses found that TGF-beta2 was present in both the serum and CSF of all animals. However, the concentration of TGF-beta2 in the CSF was less (P = 0.03) in EPM affected horses (144 pg/ml) than in normal horses (256 pg/ml). In addition, the effect of CSF from normal and EPM-affected horses on the production of interferon gamma (IFN-gamma) by PHA-P stimulated PBMCs from normal horses was investigated using a bioassay. It was found that CSF from normal and EPM-affected horses enhanced IFN-gamma activity from PHA-P stimulated peripheral blood mononuclear cells (P < or = 0.05); however, the response to CSF from EPM-affected horses was no different than the response to CSF from normal horses. Treatment of cells with anti-TGF-beta2 monoclonal antibodies slightly increased the response when co incubated with CSF from normal horses, and slightly decreased it when co incubated with CSF from EPM-affected horses. These differences, however, did not achieve statistical significance (P > 0.05). Results of this study indicated that production of TGF-beta2 is altered in horses with EPM, and that CSF appears to contain substances which alter the inflammatory reaction to plant lectins. These findings confirm the immunomodulatory properties of CSF and suggest new techniques for future research regarding the pathophysiology of EPM. PMID- 11770997 TI - Lymphocyte responses and immunophenotypes in horses with Sarcocystis neurona infection. PMID- 11770998 TI - Equine neutrophils express mRNA for tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, macrophage-inflammatory-protein-2 but not for IL-4, IL-5 and interferon-gamma. PMID- 11770999 TI - Adequacy of a concentrated equine serum product in preventing failure of immune passive transfer in neonatal foals: preliminary study. PMID- 11771000 TI - Evaluation of the nasal response to histamine provocation with acoustic rhinometry. AB - The objectives of this study were to evaluate the reproducibility of the nasal response to histamine with the acoustic rhinometer and to compare the responses in normal and rhinitic subjects. Our study comprised 10 normal and 10 rhinitic subjects. Each subject had six sessions of provocation: three with histamine phosphate at a concentration of 4 mg/mL and three with saline phosphate provocation. Basal measurements of the nasal volumes were taken initially and then at 5-minute intervals for 90 minutes. All rhinometric measurements were made bilaterally and in triplicate. The variation between the triplicate measurements (2% +/- 0.1% [95% CI]) and the variation between the basal measurements (7.3% +/- 3.1% [95% CI]) were very low in both normal and rhinitic subjects. The comparison of the average congestive response of the normal subjects revealed that they responded steadily for at least 90 minutes to histamine and saline but that the response to histamine was significantly more important. There was also a low variability in the congestive response between the subjects. The comparison of the average congestive response of the rhinitic subjects revealed that their responses were more dynamic, not steady, compared with those of the normal subjects. The response was statistically significant only in the first few intervals. The comparison of the average congestive response to saline suggests that rhinitic subjects present a more important response than normal subjects. The comparison of the average congestive response to histamine between rhinitic and normal subjects was not statistically different but was different in the shape of the response pattern. Acoustic rhinometry is a highly reproducible method for measuring nasal volume in our provocation protocol. Histamine nasal provocation leads to a pattern of congestive response that is different in normal and rhinitic subjects. Histamine nasal provocation seems to be useful in addition to the study of nasal hyperreactivity and, as such, could permit differentiation between rhinitic and nonrhinitic subjects. PMID- 11771001 TI - Failure of penicillin to eradicate group A beta-hemolytic streptococci tonsillitis: causes and management. AB - Despite the fact that group A beta-hemolytic streptococci (GABHS) is always susceptible to penicillin, bacteriologic failure occurs in up to 20% of the patients treated with penicillin, and half of these cases are also a clinical failure. Various theories have been offered to explain this phenomenon. One explanation is that beta-lactamase-producing bacteria (BLPB) "shield" GABHS by inactivating penicillin. Beta-lactamase-producing bacteria were recovered from over 75% of the tonsils of patients who had tonsillectomy for recurrent infection. The absence of interfering aerobic and anaerobic organisms in many patients may also lead to failure of penicillin therapy in these individuals. Other explanations include noncompliance with a 10-day course of therapy, carrier state, re-infection, bacterial interference, GABHS intracellular internalization, and penicillin tolerance. Penicillin is still considered the antibiotic of choice for the therapy of GABHS tonsillitis. However, antibiotics other than penicillin were found to be more effective in eradicating the infection. These included cephalosporins (of all generations), clindamycin, macrolides, and amoxicillin clavulanate. These agents were more effective than penicillin, especially in treating patients who failed previous penicillin therapy. Treatment of tonsillitis in patients who failed penicillin therapy is aimed at the eradication of the the BLPB that protect GABHS from penicillin, while preserving the oropharyngeal "protective" organisms. This review will describe the scientific and clinical data that demonstrate and explain the phenomena of beta-lactamase production and bacterial interference. PMID- 11771002 TI - Reconstruction of the posterior auditory canal with hydroxyapatite-coated titanium. AB - There are a variety of techniques for treating chronically discharging radical mastoid cavities. The purpose of this article is to report the preliminary results of an original technique for reconstruction of the posterior auditory canal using a titanium net combined with porous hydroxyapatite coating. Titanium is fixed with two screws to the mastoid tip and zygomatic root to prevent the risk of implant dislocation. Eight patients with chronically discharging radical mastoid cavities that failed medical management underwent reconstruction of the mastoid cavity using this technique. After surgery, all cases had rapid healing and good aeration of the middle ear and mastoid. One tympanic membrane reperforated, and no extrusion of the prostheses were detected clinically or on computed tomography scanning. The minimum postoperative follow-up period has been 12 months (range 12-48 months). To date, there has been no evidence of cholesteatoma recurrence. The preliminary results remain encouraging. Larger series and longer follow-up, however, are advisable to prove real validity. PMID- 11771004 TI - Clinical applications of a finite-element model of the human middle ear. AB - Computer-generated models are increasingly being used in otolaryngology for teaching purposes, preoperative planning, and clinical simulations, especially when dealing with small, complex areas such as the middle ear. One technique used to analyze the mechanics of complex models is the finite-element method, whereby the system of interest is divided into a large number of small, simple elements. The mechanical properties and applied forces are represented by functions defined over each element, and the mechanical response of the whole system can then be computed. We present a unique three-dimensional finite-element model of the human eardrum and middle ear. Our model takes advantage of phase-shift moire shape measurements to precisely define the shape of the eardrum. The middle ear geometry is derived from histologic serial sections and from high-resolution magnetic resonance microscopy of the human ear. We discuss the importance of this model in terms of understanding and teaching the mechanics of the human middle ear, simulating various pathologic conditions, and designing ossicular prostheses. PMID- 11771003 TI - Laryngotracheoplasty using the Medpor implant: an animal model. AB - OBJECTIVE: The Medpor implant (Porex Surgical, College Park, GA) is a porous polyethylene that has been used safely in areas in the head and neck. Medpor allows the in-growth of capillaries and soft tissue and reduces the risk of infection and extrusion. This study was undertaken to evaluate the use of the Medpor implant in laryngotracheal reconstruction and to compare epithelialization of the trachea following two different methods at various intervals. METHODS: Eight beagles were divided into two groups. The first group underwent laryngotracheoplasty using the Medpor implant only, whereas the second group had the Medpor implant lined with a strap muscle flap. One animal from each group was sacrificed at 5-, 7-, 9-, and 12-month intervals. The degree of stenosis, inflammation, and epithelialization were compared. RESULTS: The Medpor implant can safely be used to reconstruct the trachea in this animal model. There is less stenosis and better epithelialization when the Medpor implant is lined with a strap muscle flap. CONCLUSION: The Medpor implant can safely be used in laryngotracheal reconstruction in beagles. PMID- 11771005 TI - Acoustic basis of tuning fork tests. AB - OBJECTIVES: To obtain pilot data to determine the feasibility of supporting or refuting a theory regarding lateralization of sound in conductive hearing loss and to describe the application of this theory to other tuning fork tests. DESIGN: Controlled audiometric testing with and without a conductive hearing loss. SETTING: A tertiary medical centre. METHODS: Sound pressure levels in external auditory canals were measured during presentation of 40- and 50-dB bone conducted stimuli. Measurements were taken from five normal male subjects before and after inducing a conductive hearing loss. OUTCOME MEASURES: If sound intensity in the ear canal was greater in the unobstructed ear canal than the obstructed ear canal, the hypothesis was supported. The number of subjects required to provide definitive proof was calculated from the measured intensity difference with and without the conductive loss and the intrasubject variability of sound intensity measurements. The applicability of the theory to other tuning fork tests and auditory phenomena was explored. RESULTS AND CONCLUSIONS: A total of 600 subjects would be required to provide evidence to support our theory using this method. The acoustic impedance mismatch-reflected sound theory could be applied to other tuning fork tests, but until further proof is available, it must be considered only a theory. PMID- 11771006 TI - Formaldehyde fasciaform tympanoplasty: a reliable technique for closing large tympanic membrane perforations. AB - Formaldehyde fasciaform grafting tympanoplasty is a reliable method, in experienced hands, to close large tympanic membrane perforations. The technique involves using autogenous temporalis fascia shaped by formaldehyde cross-linking on a special fasciaform mold (Hear America, Palo Alto, CA). This study was undertaken with the objective of assessing if an otologist with less experience in using this technique could obtain comparable results. The results of the initial 23 patients treated in this manner by one surgeon between August 1996 and January 1998 are reviewed. Success was measured by the rate of closure of the tympanic membrane perforation and by functional closure of the air-bone gap. Favourable results were obtained, with complete closure of 86% of the perforations and closure of the air-bone gap to 20 dB or less in 90% of subjects when the ossicular chain was intact. The formaldehyde fasciaform tympanoplasty technique produces consistent, reliable, and reproducible results for large tympanic membrane perforations. PMID- 11771007 TI - Brush biopsy for detection of nasopharyngeal cancer. AB - The technique described above for sampling the nasopharynx requires minimal equipment, instruction, and expertise and causes minimal morbidity. Hence, it may be a valuable tool in a widespread screening program for a far too common and debilitating cancer in certain parts of the world. PMID- 11771008 TI - Laryngeal paraganglioma. PMID- 11771009 TI - Angiolymphoid hyperplasia with eosinophilia of the parotid gland. PMID- 11771010 TI - Recurrent pleomorphic adenoma of the parotid gland with cervical metastasis. PMID- 11771011 TI - Orbitofrontal cholesterol granuloma. PMID- 11771012 TI - Diagnosis of neurofibromatosis type 2 in a patient with long-standing bilateral sensorineural hearing loss. PMID- 11771013 TI - An unusually large esophageal foreign body: a live whole fish. PMID- 11771014 TI - Ceruminous adenocarcinoma: a rare tumour of the external auditory canal. PMID- 11771015 TI - General otolaryngology in academia: past, present, future. PMID- 11771016 TI - Magnetic resonance imaging of the paranasal sinuses: incidental abnormalities and their relationship to patient symptoms. AB - OBJECTIVES: Magnetic resonance imaging (MRI) is able to demonstrate a wide range of abnormalities in the paranasal sinuses, which are often reported as incidental findings on scans performed for indications other than the evaluation of paranasal sinus pathology. However, the clinical significance of these findings remains undefined. We present a prospective study that determines the prevalence of abnormalities in the paranasal sinuses in a population undergoing MRI scans for suspected intracranial disease. These findings are correlated with clinical data pertaining to nasal and sinus symptoms. STUDY DESIGN: Prospective, cross sectional study. METHODS: Patients undergoing MRI scans for suspected intracranial pathology were asked to complete a questionnaire pertaining to symptoms of nasal/sinus pathology. The T2-weighted scans of 86 patients (mean age = 51 years) were then reviewed for evidence of paranasal sinus pathology using a standardized method for evaluation and reporting of results. These results were then correlated with those obtained from the patient questionnaire. RESULTS: Radiologic abnormalities were found in the paranasal sinuses of 33 (38%) patients. Abnormalities were most commonly seen in the ethmoid sinuses (44.8%) followed by the maxillary (38%), sphenoid (14%), and frontal (3%) sinuses. Analysis of the clinical data revealed no significant relationship between the presence of clinical symptoms of nasal and sinus pathology and abnormalities on MRI scan. CONCLUSION: The assessment of inflammatory sinus pathology remains controversial. Based on the results of this study, incidental abnormalities of the paranasal sinuses detected on MRI scan do not appear to be related to clinical symptoms. PMID- 11771017 TI - Effects of passive smoking on odour identification in children. AB - BACKGROUND AND OBJECTIVE: The effect of passive smoking on odour identification in children has rarely been reported. This study assessed the ability of such young subjects to identify a variety of odours. METHODS: The study population consisted of 20 children, 10 who were exposed to passive smoke at home and 10 with nonsmoking parents. Ten odourants were tested: vinegar, ammonia, peppermint, roses, bleach, vanilla, cough drops, turpentine, licorice, and mothballs. Each child was presented with five test trays containing all 10 odourants in random order. RESULTS: Of the total of 500 odours presented, the control group correctly identified 396 (79%) and the study group identified 356 (71%) (p < .005). The study group tended to misidentify 4 of the 10 odourants tested, namely, vanilla, roses, mothballs, and cough drops-56 of 200 (28%), compared with 96 of 200 (48%) in the control group. This was a highly significant finding (p < .0005). CONCLUSION: This work demonstrated that children exposed to passive smoke have difficulty identifying odours in comparison with children raised in relatively smoke-free environments. The identification of four odourants, vanilla, roses, mothballs, and cough drops, was particularly diminished in this study group. PMID- 11771018 TI - Predictability of hypocalcemia using early postoperative serum calcium levels. AB - OBJECTIVE: In operations involving the thyroid or parathyroid glands, postoperative serum calcium levels are one contributing factor to patients' length of hospital stay. In this study, we wanted to determine whether early postoperative serum calcium levels could be used to predict hypocalcemia following operations of the thyroid or parathyroid glands. METHODS: A retrospective chart review was performed on 203 patients who had undergone operations involving risk to the parathyroid glands. This included patients who had bilateral thyroid operations or those who had one or more parathyroid glands removed for various disease processes. Postoperative calcium levels were plotted as a function of time, and the slope between the first two levels was examined. Both serum calcium levels were drawn within 12 hours after the operation. RESULTS: A positive slope predicted normocalcemia in 100% of patients undergoing thyroid or parathyroid procedures. A negative slope was predictive in magnitude. Patients who developed hypocalcemia had an average slope two to three times more negative than those remaining normocalcemic. CONCLUSIONS: It appears that early serum calcium levels may be predictive for postoperative hypocalcemia in operations that put the parathyroid glands at risk. PMID- 11771019 TI - Outcome of curative management of malignant tumours of the parotid gland. AB - PURPOSE: The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed. MATERIALS AND METHODS: A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour. RESULTS: All patients were initially managed with a parotidectomy, and postoperative x-ray radiation therapy (XRT) was administered to 159 patients. The actuarial 5-year cause-specific survival and locoregional control rates were 76% and 81%, respectively. The survival and locoregional control rates for patients treated with surgery alone versus surgery plus postoperative XRT were not statistically different. A multiple regression analysis identified only age and tumour category to be independently significant prognostic factors for both survival and locoregional control. CONCLUSION: We would recommend that patients with malignant parotid gland tumours be managed with parotidectomy, followed by postoperative XRT for tumours with residual disease, aggressive histology, and/or positive lymph nodes. PMID- 11771020 TI - Are all atypical positional nystagmus patterns reflective of central pathology? AB - In this retrospective clinical study, 20 patients were identified to have atypical positional nystagmus associated with positional vertigo following a thorough history and otoneurologic examination. All patients underwent either computed tomography or magnetic resonance imaging. Eight patients demonstrated radiologic evidence of intracranial pathology; the majority had clinical findings suspicious for central pathology. Of 12 patients with normal intracranial imaging, none had a history or clinical findings suspicious for central pathology. The results of this study suggest that in the absence of clinical findings suspicious for central pathology, atypical positional nystagmus in isolation does not necessarily need to be investigated for central lesions. Clinical review of this patient population, however, is required to determine if there is resolution or evaluation to a recognizable form of inner ear dysfunction. PMID- 11771021 TI - Management of the neck in N0 squamous cell carcinoma of the oral cavity. AB - Mortality in treated squamous cell carcinoma of the oral cavity is most often owing to locoregional failure. In an attempt to improve survival, an aggressive approach to surgical management is often favoured. Although it is generally accepted that the N0 neck should be treated if the risk of micrometastatic disease exceeds 20%, there is little direct support in the literature for this position. A retrospective review of all patients presenting with T1-2, N0 squamous cell carcinoma of the oral cavity treated at the Cancer Control Agency of British Columbia from 1985 to 1994 was conducted. Patients were followed for a minimum of 5 years with documentation of patterns of recurrence and disease specific survival relative to initial management. The decision regarding management of the neck was frequently made to accommodate treatment of the primary site or reconstructive strategies. Thirteen percent of patients with T1, N0 disease underwent prophylactic neck dissection. No significant difference in outcome was noted in this group. Thirty-three percent of patients with T2, N0 disease underwent prophylactic neck dissection. There was a trend toward improved 5-year survival and lower recurrence rates in the group whose necks were treated, but the difference was not found to be statistically significant. In conclusion, this review showed a trend toward increased survival with prophylactic treatment of the neck in T2, N0 squamous cell carcinoma of the oral cavity, but a larger study would be needed to show a statistically significant benefit. PMID- 11771022 TI - Hearing loss in rheumatoid arthritis. AB - OBJECTIVE: Hearing loss, both sensorineural and conductive, has been reported in patients with rheumatoid arthritis (RA). The aim of this study was to try and ascertain the type of hearing loss and to determine the cause for any conductive element noted in these cases. DESIGN AND SETTING: A prospective case-control study in the otolaryngology department of a university teaching hospital in the United Kingdom. METHODS AND OUTCOME MEASURES: This study compared 35 patients with RA with 35 age- and sex-matched controls. All patients had pure-tone audiometry, speech discrimination, tympanometry, acoustic reflex, and acoustic reflex decay carried out. Statistical analysis of the two groups was carried out using the F test for differences in variation and the t-test for independent samples. RESULTS: Sensorineural hearing loss that was statistically significant (p < .05) at 500 Hz, 1 kHz, and 2 kHz in both ears was found in 60% of the RA group and in 34.29% of the control group. A conductive hearing loss that was statistically significant (p < .05) at 250 Hz, 500 Hz, 1 kHz, and 2 kHz in the right and left ears was found in 17.14% of the RA patients and in 5.71% of the control group. Speech discrimination did not show a statistically significant difference between the two groups. Tympanometry showed that the conductive element was probably owing to laxity of the middle ear transducer mechanism. Acoustic reflex and reflex decay did not show statistically significant differences between the two groups. CONCLUSION: Sensorineural hearing loss of the cochlear variety is a common finding in patients with RA, whereas conductive loss, although seen, is much less common. Increased laxity of the middle ear transducer mechanism is the likely cause of the conductive element. PMID- 11771023 TI - Treatment outcomes of benign paroxysmal positional vertigo. AB - OBJECTIVE: The purpose of this study was to examine the efficacy of the particle repositioning manoeuvre (PRM) in the treatment of benign paroxysmal positional vertigo (BPPV). DESIGN: A randomized prospective study of patients with BPPV. METHODS: Seventy-one patients were randomized to one of three groups at their first clinic visit. These groups included the PRM, a sham PRM, and a control group. Patients were followed up in clinic at 2 weeks and 3 months. The mean long term follow-up was 12 months. A telephone questionnaire was also conducted. RESULTS: At 2-week follow-up, 81.8% of patients in the PRM group had a resolution of symptoms and a negative Dix-Hallpike test compared with 15.3% in the sham PRM group and 60% in the control group. This difference was statistically significant between the treatment (PRM) and sham PRM groups and between the sham and control groups. It nearly reached significance between the treatment and control groups (p = .06). The sham treatment group had by far the worst outcome at the 2-week interval. There was no statistically significant difference between the groups after 2 weeks. CONCLUSION: The PRM is side specific. It may help induce remission of the vertiginous symptoms of BPPV in the short term. This cannot be attributable to a placebo effect. The PRM does not seem to affect the natural history of the disorder in the long term. The sham treatment causes a delay in spontaneous recovery, possibly by preventing the particles from falling into the utricle. This study has not compared the frequency or severity of symptoms. PMID- 11771024 TI - Efficacy of amitriptyline in the treatment of subjective tinnitus. AB - We investigated the effect of amitriptyline, a tricyclic antidepressant, on patients with subjective tinnitus. The study group consisted of 37 adult patients admitted to the Ear, Nose, and Throat and Audiology Department of Hacettepe University. The amitriptyline group consisted of 20 patients and the placebo group consisted of 17 patients. All of the patients were evaluated using a questionnaire, audiologic evaluation, high-frequency audiometry, impedancemetric tests, auditory brainstem response, tinnitus frequency, and loudness matching assessed by audiometric methods at the beginning and end of the study. The patients in the amitriptyline group received 50 mg/day amitriptyline in the first week and 100 mg/day for the following 5 weeks. In the placebo group, the patients received tablets consisting of lactose starch for 6 weeks, with a dosage of 1 tablet/day. The subjective complaints of the patients in the amitriptyline group decreased, and the "present" symptoms resulted in fewer complaints. The severity of tinnitus decreased in the amitriptyline group by means of subjective and audiometric methods. In the placebo group, no significant change was observed. The success of treatment was 95% in the amitriptyline group and 12% in the placebo group. Amitriptyline therapy was concluded to be effective. PMID- 11771025 TI - Stylalgia: an Indian perspective. AB - OBJECTIVE: The main objective was to study the stylalgia profile in Indians and the outcome of styloidectomy in such cases. DESIGN: This prospective study was carried out by random selection of patients with stylalgia using periodic random numbers. SETTING: This was a hospital-based study. METHODS: Surgical excision of the symptomatic enlarged styloid process was performed by the transtonsillar route using a dilation and curettage (D and C) curette. MAIN OUTCOME MEASURES: The patients were followed postoperatively for their pain relief. RESULTS: Of 40 patients operated on, 31 (77.5%) became symptom free, 5 (12.5%) had considerable improvement in their symptoms, and 4 (10%) had no relief. CONCLUSIONS: The incidence of an enlarged styloid process was found to be higher in an Indian rural population with female preponderance owing to their carrying of heavy weight on head. Styloidectomy was very rewarding. The D and C curette was found to be a very effective instrument for styloidectomy. PMID- 11771026 TI - Hearing preservation in acoustic neuroma surgery. AB - This article reviews the Montreal experience of hearing preservation in acoustic neuroma surgery. The medical records since 1995 of 36 patients who underwent acoustic neuroma extirpation with the intent to preserve hearing were examined. Intraoperative monitoring was conducted using auditory brainstem response measurement with electrocochleography via a transtympanic electrode. The role of intraoperative monitoring in guiding surgical technique and its correlation with postoperative hearing outcome are discussed. A review of the literature regarding hearing preservation in acoustic neuroma surgery is included. PMID- 11771027 TI - Early diagnosis of papillary tumour of the endolymphatic sac. PMID- 11771028 TI - Radiofrequency tissue reduction of the palate in patients with moderate sleep disordered breathing. AB - OBJECTIVE: Radiofrequency volumetric reduction of the palate has been advocated as a treatment for mild sleep-disordered breathing (SDB). Our study examines the efficacy of this procedure on patients with mostly moderate SDB. DESIGN: Prospective, nonrandomized, consecutive series. SETTING: St. Boniface Hospital, Sleep Disorders Centre, University of Manitoba, Winnipeg. METHOD: Twelve patients with polysomnographically proven moderate SDB were given a total of 2400 to 3600 joules of radiofrequency energy to their soft palate over two to three treatments. Follow-up examined the effect of treatment on subjective and objective parameters including the Epworth Sleepiness Scale, loudness of snoring, Apnea-Hypopnea Index (AHI), and Arousal Index. RESULTS: Two of 12 patients had a good objective response to treatment in that their AHI dropped by more than 50% and to a value of less than 20. However, none of the patients claimed to have a satisfactory subjective response. There was a slight reduction in the mean AHI from 31.2+/-5.1 to 25.3+/-4.2 (p < .05), but no clinically significant difference was found between pre- and post-treatment groups with respect to other sleep parameters. There was no improvement in daytime sleepiness or snoring. CONCLUSIONS: Radiofrequency tissue ablation of redundant soft palate tissues lacks clinical efficacy in patients with moderate SDB. PMID- 11771029 TI - Success rates in paediatric tympanoplasty. AB - OBJECTIVE: To determine if the success of paediatric tympanoplasty is dependent on certain criteria, which are determinable prior to surgery. DESIGN: Retrospective chart review. SETTING: An academic paediatric otolaryngology department. PATIENTS: Seventy-seven patients who had undergone tympanoplasty with or without ossicular reconstruction, but without mastoidectomy, between April 1997 and May 1999. MAIN OUTCOME MEASURES: Status of the repaired tympanic membrane at last follow-up visit measured by otoscopic examination and with tympanometry. RESULTS: Eighty-nine tympanoplasties were performed during this period. The age range was 2.9 to 22 years. The success rate was 75% overall. For patients younger than 11 years (n = 43), the success rate was 82%, and for those 11 to 18 years (n = 44), it was 74%, which was not significantly different. In 18 patients 7.5 years or younger, the success rate was 79%. Perforation location, size, presence of myringosclerosis, status of the other ear or nose, history of the perforation, surgical approach, middle ear findings, canal packing, and gender were not shown to be significantly different between successful and unsuccessful tympanoplasty groups. CONCLUSION: These young patients had a good success rate post-tympanoplasty, which we believe reflects less severe disease. These results mitigate against delaying tympanoplasty in young children. PMID- 11771030 TI - An aggressive approach to the surgical management of suspicious thyroid nodules. AB - Thyroid cancer accounted for about 2.5% of all new cancers among Canadian females in the year 2000. The surgical management of well-differentiated thyroid cancer remains controversial. We reviewed 100 consecutive cases of total thyroidectomy for thyroid masses suspicious for malignancy done between 1998 and 1999. When feasible, a capsular dissection was performed using only the bipolar cautery for hemostasis. The accuracy of preoperative diagnosis and complications of surgery are evaluated. We suggest that total thyroidectomy can be performed, without excessive morbidity. If performed for all suspicious thyroid nodules, it will eliminate the need for completion thyroidectomies and high ablative does of 131I. PMID- 11771031 TI - Reliability of the Sunnybrook Facial Grading System by novice users. AB - OBJECTIVES: To evaluate the intrarater and inter-rater reliability of the Sunnybrook Facial Grading System (SFGS) by novice users. DESIGN: Prospective interval study using one measurement instrument. SETTING: Tertiary teaching hospital (Sunnybrook & Women's College Health Science Centre). METHODS: Twenty two patients with a wide spectrum of facial dysfunction recorded on videotapes were rated using the SFGS by eight novice observers independently in two different sittings separated by 3 weeks. The order of patients was randomized for the second sitting. Intraclass correlation coefficients were calculated for component scores and for total scores within and between raters. RESULTS: The intrarater reliability coefficients for the eight raters ranged from .838 to .929. This largely overlaps with the data obtained in previous studies with expert raters. The inter-rater reliability for all eight raters at time 1 was .982 and for time 2 was .970. This is higher than what was previously obtained with expert raters. CONCLUSION: The SFGS is as reliable when applied by novice users as by expert users. PMID- 11771032 TI - Does laser-assisted uvulopalatoplasty work? An objective analysis using pre- and postoperative polysomnographic studies. AB - INTRODUCTION: Since its introduction in 1990, the procedure of laser-assisted uvulopalatoplasty (LAUP) has become a popular alternative to UP3 and other surgical procedures for sleep-disordered breathing. Laser-assisted uvulopalatoplasty has proved to be a relatively simple and cost-effective alternative; however, after almost a decade of use on thousands of patients and many studies that show subjective benefits, very few patients have been followed objectively. PURPOSE: Our purpose was to study in an objective, prospective manner the effects of LAUP on snoring volume and duration as well as on apnea index, respiratory disturbance index (RDI), and desaturation index. METHODS: Fifty consecutive patients were evaluated for sleep-disordered breathing; 43 patients were included in the study, and all had pre- and post-LAUP polysomnograms. Patients were divided into groups depending on their preoperative RDI. All subjects had a pre-LAUP history and physical examination and an otolaryngologic examination, including fibre-optic endoscopy. All patients had a preoperative polysomnographic evaluation. An in-office LAUP using CO2 laser and local anaesthetic was performed on all patients, and all had post-LAUP polysomnography an average of 9.4 weeks postoperatively at the same sleep centre. RESULTS: Overall, we found a significant improvement in 60% of patients, with the greatest benefit in patients with a preoperative RDI of greater than 40 per hour. Patients with preoperative RDI < 20 were successfully treated in only 25% of cases. PMID- 11771033 TI - Effect of residual hearing prior to cochlear implantation on speech perception in children. AB - We examined the impact of residual hearing prior to cochlear implantation on pre- and postimplantation speech perception outcomes in children. Stimulation of the auditory system prior to implantation because of the presence of residual hearing is important for development of the central auditory pathways, whereas, in the absence of such stimulation, the pathways show less development. We hypothesized that children who had some degree of residual hearing preimplantation achieve better speech perception skills than their peers with poorer hearing. From the 133 children followed in our program, we identified 37 children who had an audiometric pure-tone average of better than 95 dB HL in the better ear at any time preimplantation. Psychophysical speech perception measures, the Word Identification Picture Inventory and the Phonetically Balanced Kindergarten list, in these children were compared with those of 96 implanted children who had poorer hearing prior to implantation. Children with more residual hearing showed higher speech perception scores both before implantation and over their first year of implant use than children with poorer hearing, suggesting that there is an advantage in having a greater degree of residual hearing preimplantation. We suggest that this advantage is promoted, in part, by the greater potential for auditory stimulation provided by high-gain hearing aids in children with greater degrees of residual hearing. This advantage appears to be maintained at least over 1 year postimplantation, yet the rates of development of postimplantation speech perception are not different between the groups. We suggest that this may be due to the unique aspects of electrical stimulation from a cochlear implant. Our findings suggest that it is important to minimize the delay of speech perception skills in the preimplantation phase, particularly in children with poor residual hearing. This can be accomplished by implanting children with congenital severe to profound hearing loss at young ages and children with acquired hearing loss soon after the onset. Also, auditory stimulation prior to implantation should be maximized through the consistent use of hearing aids and therapy that emphasizes development of auditory skills. PMID- 11771034 TI - Partial labyrinthectomy approach for brainstem vascular lesions. AB - Conventional wisdom has typically dictated that the bony labyrinth is an inviolate structure. This notion, however, was successfully challenged following the introduction of the partial labyrinthectomy approach, which was primarily used for the surgical management of cerebellopontine and petrous apex meningiomas. In this article, we discuss an extension of the technique of partial labyrinthectomy in a series of patients that has been used for the treatment of brainstem vascular lesions. We believe that this technique provides superior exposure to the brain stem when compared with conventional retrosigmoid and retrolabyrinthine approaches while reducing the inherent morbidity seen in transotic or petrosectomy approaches. PMID- 11771035 TI - Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification. AB - OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system. PMID- 11771036 TI - Detection, evaluation, and management of aspiration in rehabilitation hospitals: role of the otolaryngologist--head and neck surgeon. AB - CONTEXT: Reductions in the length of acute care hospitalizations have resulted in earlier transfer of patients with significant neurologic disease, such as head injury or stroke, to inpatient rehabilitation facilities. In many instances, these patients arrive at the rehabilitation hospital with multiple unresolved acute processes, including undetected or inadequately evaluated dysphagia. These patients may be at significant risk for the development of aspiration pneumonia, especially if elderly or debilitated. OBJECTIVE: To review the role of otolaryngologic consultation in the management of inpatients in two rehabilitation hospitals. DESIGN AND SETTING: Retrospective review of 1046 consultations performed by two otolaryngologists over a 4-year period at two long term inpatient rehabilitation hospitals in the Pittsburgh, PA, metropolitan area. RESULTS: A total of 833 patients were evaluated. Three hundred were seen for a variety of common disease processes, including hearing loss, and cerumen removal. A total of 548 consultations were for recommendations regarding swallowing dysfunction. Fibre-optic endoscopic examination of swallowing function was performed in 478 patients. Two hundred consultations were for assistance in decannulation of patients who were transferred from the acute care hospital with an indwelling tracheostomy tube. CONCLUSIONS: The detection and evaluation of the aspiration risk of dysphagic patients in rehabilitation hospitals are enhanced by an onsite dysphagia team with access to instrumented measures of swallowing, especially videofluoroscopy or videoendoscopy. Otolaryngologic consultation can provide considerable benefit for many inpatients in rehabilitation hospitals, even those with apparent "minor" dysfunction. The otolaryngologist-head and neck surgeon is uniquely qualified to provide consultation in the management of those inpatients with complex clinical problems involving the upper aerodigestive tract. Consultation may be critical for some patients, assessing the cause and severity of dysphagia and assisting in the safe decannulation of those with indwelling tracheostomy tubes. PMID- 11771037 TI - Use of radiotherapy for control of sialorrhea in patients with amyotrophic lateral sclerosis. AB - Many patients with amyotrophic lateral sclerosis (ALS) develop progressive difficulty with swallowing secretions, and drooling becomes a significant problem. The production of saliva can be reduced with radiation of the submandibular and sublingual salivary gland tissue. This method has been used successfully in Europe and had limited use at Vancouver Hospital. This study was undertaken to determine the lowest effective dose of radiation necessary to control salivary production. Over a 3-year period, patients with ALS who developed significant problems with drooling were identified and treated with a predetermined dose of radiation. The first group received a single dose of 8 Gy in one fraction and the second received a total of 12.5 Gy in two fractions. They were followed over the next 6 months and were evaluated for effectiveness and side effects. Their saliva was measured pre- and postradiation treatment, and they were also asked to evaluate the change subjectively, using a questionnaire. The preliminary findings suggest that 8 Gy of radiation was effective in controlling drooling, and increasing the dose did not improve initial control. Long-term control was difficult to evaluate as the patients entered in the study were very ill and their life expectancy was very short. Radiation at this low dose resulted in very few side effects. Low-dose radiation can safely help control secretions in selected patients with ALS. PMID- 11771038 TI - Fluctuating sensorineural hearing loss associated with the menstrual cycle. PMID- 11771039 TI - Bilateral lateral sinus thrombosis associated with otitis media and mastoiditis. PMID- 11771040 TI - Effects of head and neck radiation therapy on vocal function. AB - OBJECTIVE: Radiotherapy (RT) is used to treat a variety of head and neck malignancies. The larynx may receive high radiation doses even in the absence of disease. The effects of RT on the nondiseased larynx are unknown. This study will evaluate subjective and objective parameters of vocal function in patients treated with RT for nonlaryngeal malignancies. DESIGN: Cross-sectional observational study. METHODS: Videostroboscopic, aerodynamic, and acoustic analyses were performed. Results were compared to age- and gender-matched controls. Self-assessment of voice quality was measured using the Voice Handicap Index. RESULTS: A majority of patients demonstrated increased supraglottal activity (i.e., ventricular fold constriction) during stroboscopic evaluation. Significant differences compared to normative data were found in many aerodynamic and acoustic parameters. A substantial proportion (27%) of patients reported significant voice handicap. Younger patients reported greater handicap, and voice quality was worse with time. CONCLUSIONS: Significant objective and subjective changes in vocal function occur in patients radiated for nonlaryngeal head and neck malignancies. Young patients may have the worst impact, and vocal dysfunction may increase with time. A prospective study of this patient population should include a baseline voice quality assessment. PMID- 11771041 TI - Metastatic hypernephroma to the head and neck: unusual case reports and review of the literature. AB - Hypernephroma is one of the most common tumours to spread by extranodal metastases to the head and neck. We herein report on six patients with unusual metastatic hypernephroma to the head and neck area. In two of the six cases, the metastatic tumour in the head and neck was the presenting symptom, and the renal tumour was secondarily detected. Metastatic hypernephroma to the head and neck area has been demonstrated mostly in the paranasal sinuses, parotid gland, and the mandible. Among the six cases presented, four belong to the above-mentioned group, but the other two are rather rare cases, one metastatic to the nasopharynx and soft palate and the other to both lobes of the thyroid gland. Hypernephroma should be sought and excluded whenever a metastatic lesion is encountered in the head and neck area, even if the metastatic lesion is the first clinical presentation. The diagnosis of metastatic hypernephroma should be suspected in any patient with even a remote history of renal cell carcinoma. PMID- 11771042 TI - Cardiovascular safety of cocaine anaesthesia in the presence of adrenaline during septal surgery. AB - OBJECTIVE: The purpose of this study was to investigate the possible cardiovascular side effects of 4% cocaine solution in the presence of adrenaline during septal surgery. METHOD: Sixty adult patients undergoing elective septal surgery with local anaesthesia were included in the study. Noses were packed with 5-mL 4% cocaine (200-mg) solution on cotton pledgets, which were left in the nose for 15 minutes. Then, 10 mL of local anaesthetic (lidocaine 2% and adrenaline 1:100,000) were infiltrated in septal mucosa, and 15 minutes later, the surgical procedure was initiated. At the beginning of the operation, intervals from 12 lead surface electrocardiograms and vital signs including blood pressures and heart rate were recorded as a baseline. All measurements were repeated just before local anaesthetic infiltration, just before the beginning of the surgical procedure, and, finally, at the end of the operation. All four measurements and electrocardiographic tracings were examined. Systolic and diastolic blood pressures and QT parameters, RR intervals, and heart rates obtained from electrocardiogram were compared statistically with repeated-measures analysis of variance. RESULTS: No statistically significant difference was found among all four staged measurements. None of the patients developed tachycardia, hypertension, hypotension, or any chest pain. In electrocardiogram tracings, no sinus tachycardia depression, elevation, or bundle branch block was noted. CONCLUSION: This study shows that concomitant use of cocaine and adrenaline in the proper concentration and volume and in a carefully screened patient group was safe for the cardiovascular system. PMID- 11771043 TI - Endoscopically assisted diagnosis and treatment of maxillofacial fractures. AB - The increased availability of endoscopic instrumentation has enabled a number of surgeons to re-evaluate certain traditional open approaches to the treatment of multiple medical conditions. Our favourable early experience with the use of endoscopes in maxillofacial traumatology will be reviewed. PMID- 11771044 TI - Ceruminolytic efficacy in adults versus children. AB - OBJECTIVES: An inexpensive, nontoxic ceruminolytic with reasonable efficacy that can be used by the patient or their caregivers at home could represent significant financial saving for patients and health care systems. The purpose of this study was to compare two simple ceruminolytics for in vitro efficacy. STUDY DESIGN: Randomized controlled trial. METHODS: Thirty-six children and 33 adults presenting to a community family practice clinic who had cerumen occluding at least one external auditory canal were randomly assigned to compare use of 10% aqueous sodium bicarbonate and 2.5% aqueous acetic acid as ceruminolytics in occlusive cerumen. RESULTS: We were unable to demonstrate a difference between in vivo efficacy of these two ceruminolytic solutions, but both solutions were significantly more efficacious in children than adults. CONCLUSIONS: There is a role for these ceruminolytics in children with occlusive cerumen, but adults would be better treated in another way. PMID- 11771045 TI - Cathepsin L activity and its inhibitor in human otitis media. AB - OBJECTIVE: We examined cathepsin L activity, expression of cystatin A, and copper and zinc-containing superoxide dismutase in human chronic otitis media. The relationships of our findings to clinical findings (e.g., grade of bone destruction) were also studied. DESIGN: Retrospective basic and clinical study. SETTING: Department of Otolaryngology and First Department of Biochemistry, Kinki University School of Medicine, Osaka, Japan. METHOD: The human middle ear tissues evaluated in this study were surgically obtained from seven patients with cholesteatoma epithelium, three patients with granulation tissues in cholesteatoma, three patients with granulation tissues in noncholesteatoma, and three patients with intact mucous membrane of the middle ear. MAIN OUTCOME MEASURES: Cathepsin L activities in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma were measured using Barrett's method. Cystatin A expressions were observed by Western blot analysis. Copper- and zinc-containing superoxide dismutase in cholesteatoma was examined immunohistochemically. RESULTS: Mean cathepsin L activity was higher in diseased tissues than in intact mucous membranes of the middle ear. Granulation tissues with high cathepsin L activity resulted in extensive bone destruction in both cholesteatomas and noncholesteatomas of the middle ear. All cases with intact mucous membrane of the middle ear exhibited no expression of cystatin A. Seven of 10 cases with diseased tissues expressed cystatin A in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma. No relationships were found between cystatin A expression and grade of cathepsin L activity. Copper- and zinc-containing superoxide dismutase was more strongly positive in cholesteatoma epithelium regions than in granulation tissues. CONCLUSION: These results suggest that copper- and zinc-containing superoxide dismutase in cholesteatoma epithelium prevents complications by suppressing cathepsin L activity. PMID- 11771046 TI - The bulla ethmoidalis: lamella or a true cell? AB - BACKGROUND: The anterior ethmoidal region, including the bulla ethmoidalis, is the most common area addressed during functional endoscopic sinus surgery. Therefore, a detailed understanding of the bulla is essential for safe and effective surgery. HYPOTHESIS: Based on a review of historical articles on sinus anatomy and review of the current understanding of sinonasal embryology, it is suggested that the ethmoidal bulla is a "lamella" structure rather than a "cell," as it is widely accepted to be. OBJECTIVE: To analyze the anatomic conformation and nature of the ethmoidal bulla. METHODS: Detailed gross anatomic sagittal dissection of 14 sinonasal complexes with special attention to the ethmoidal bulla and surrounding structures and pneumatization tracts. RESULTS: The ethmoidal bulla consisted of a distinct bony lamella in all cases. The degree of development and pneumatization was variable, ranging from a rudimentary torus to a relatively well-pneumatized "bulla"-like structure. A pneumatization tract originating from the retrobullar recess was present in all specimens. This pneumatization excavated into the lamella, creating the bulla-like appearance as viewed from the middle meatus. However, the bulla was not a discrete individual ethmoid cell as it did not have a complete or discrete posterior bony wall. Rather, the posterior wall of this pneumatization tract was formed by the basal lamella. CONCLUSION: The ethmoidal bulla lacks a distinct posterior wall and therefore is not a separate cell but rather a bony lamella with an air space behind it. From an anatomic perspective, bulla is perhaps not the best term for this structure. PMID- 11771047 TI - Analysis of human papillomavirus in schneiderian papillomas as compared to chronic sinusitis and normal nasal mucosa. AB - Schneiderian papillomas (SPs) are tumours arising from the surface epithelium (schneiderian epithelium) of the nasal cavity and paranasal sinuses. Evidence points toward a viral etiology, specifically human papillomavirus (HPV). Although substantial data indicate HPV as a likely etiology, little is known about the role of HPV in benign nasal pathologies or in normal nasal mucosa. The objective of this study was to characterize the relationship between HPV and SP, chronic sinusitis (CS), and normal nasal mucosa. A case-control study was undertaken, matching patients with SP to patients with CS. Patients with normal nasal mucosa served as a control group. All patients had their tissues analyzed for the presence of various HPV subtypes using line blot assay. A total of 168 patients were identified (74 SP, 74 CS, 20 control). Of these, 70 (41.7%) had detectable deoxyribonucleic acid and 9 of 70 (12.9%) had detectable HPV of subtypes 6, 11, and 16. None had detectable HPV type 18. Significant differences were detected in the presence of HPV in the CS, SP, and control groups, as well as in the presence of low- versus high-risk subtypes among investigation and control groups. Significant differences exist in HPV infectivity among SP, benign nasal pathologies such as CS, and normal nasal mucosa. Human papillomavirus plays an important role, at least in part, in the development of SP, with types 6, 11, and 16 being more pivotal than other types. Line blot assay is a useful technique in identifying HPV in SP. PMID- 11771048 TI - Comparison of craniofacial skeletal characteristics of infants with bilateral choanal atresia and an age-matched normative population: computed tomography analysis. AB - Choanal atresia (CA) results from the developmental failure of the posterior nasal cavity to communicate with the nasopharynx. Computed tomographic (CT) scanning is often used as a diagnostic tool for CA as it is able to provide information regarding the extent and type of atresia. Studies have used CT measurements to analyze the skeletal deformities of children with CA. Computed tomographic analysis of the complete craniofacial skeletal characteristics of children with CA has not been previously reported. This study analyzed the craniofacial skeletal characteristics of infants with bilateral choanal atresia (BCA) and compared them with age-matched standards. Eight patients with BCA under the age of 3 months were evaluated. Fourteen cranio-orbitozygomatic variables were used to represent the craniofacial skeletal configuration. The measurements from the control group were compared with the available values of age-matched normal controls. Statistically significant differences between the means of the sample group and control group were demonstrated in 10 of 14 variables. The sample group means were consistently smaller than the control group mean. Detailed knowledge of the underlying anatomy of infants with BCA will help in the development of treatment strategies and will provide data for evaluation of operative intervention on craniofacial growth. PMID- 11771049 TI - Intraoperative management of the thyroid gland in laryngeal cancer surgery. AB - OBJECTIVE: To determine if it is necessary to perform a hemithyroidectomy routinely with all total laryngectomies or if it should be reserved for selected cases. DESIGN: A retrospective analysis of 215 cases who had been operated on due to laryngeal cancer in our clinic between 1985 and 1999. SETTING: In only 182 cases, hemithyroidectomy and isthmectomy were performed together with laryngeal surgery. Of these, 98% were male. Their ages ranged between 42 and 70 years. The tumour was located in the supraglottic region in 93 (51%) and in the glottic region in 24 (13%) cases. In 65 cases (36%), the tumour was transglottic. Twenty cases of transglottic tumours (31%) and 3 cases of glottic tumours (12.5%) were found to have subglottic extension. METHODS: Total laryngectomy with unilateral or bilateral neck dissection and hemithyroidectomy on the tumour side plus isthmectomy were performed on all patients. On the pathologic specimens, subglottic extension was measured anteriorly and posteriorly from the free edges of the vocal cords. The specimens were stained with hematoxylin and eosin and examined under a light microscope. MAIN OUTCOME MEASURES: With glottic and transglottic carcinomas, the need for thyroidectomy may be based on the intraoperative assessment of the thyroid gland. In subglottic carcinomas, a hemithyroidectomy should routinely be performed. There may be no need to perform thyroidectomy in all total laryngectomy cases. RESULTS: The thyroid gland was invaded by squamous cell carcinoma in only 2 cases (1%). Both of these cases were transglottic tumours staged as T3 and T4 and had a subglottic extension more than 1 cm. CONCLUSIONS: We recommend routine hemithyroidectomy and isthmectomy during total laryngectomy only in cases with subglottic extensions more than 1 cm or thyroid cartilage invasion with tumour. In the other cases, assessment of extralaryngeal invasion and thyroid gland invasion by the tumour will determine whether thyroidectomy should be performed. PMID- 11771050 TI - Unilateral sixth cranial nerve palsy caused by skull base mass lesions: case series. PMID- 11771051 TI - Neuro-otologic findings in a case of superficial siderosis with bilateral hearing impairment. PMID- 11771052 TI - Employees at midlife: crisis or transition? PMID- 11771053 TI - Buoying morale and productivity during layoffs. PMID- 11771054 TI - Health affects work, and work affects health. PMID- 11771055 TI - At work with the CDC. Business & tobacco. PMID- 11771056 TI - When behavioral health benefits count. PMID- 11771057 TI - Applied wellness. PMID- 11771058 TI - Data watch. The state of employer-sponsored health insurance. PMID- 11771059 TI - Health care privacy: preparing for the brave new world, Part II. AB - Are you ready to talk privacy with your patients? Physicians need to be. In the not-too-distant future, health providers will be required by federal law to describe their information-management practices to most people who seek care. In addition, new regulations require specific types of informed patient permissions- notably written "consents" and "authorizations"--before certain information may be used or disclosed. This article, the second of a four-part series on how federal privacy regulations will affect the day-to-day lives of physicians and their staffs, outlines what you need to know about notices and permissions for these "informed discussions." PMID- 11771060 TI - Your money should be working harder: the power of compound interest. AB - In light of the recent stock market volatility, many physicians may feel compelled to re-evaluate the progress they've made toward their goal of financial independence. Those who have planned proactively understand the importance of accumulating assets in order to have a specific amount available at the time of retirement capable of generating sufficient income over their lifetime. Regardless of whether that magic number is $1.5 million, $4 million or somewhere in between, it is critical to understand the methods of wealth accumulation that will allow you to achieve your specific goal in the quickest and most efficient manner. While we have no control over the performance of the various equity (stock) and fixed income (bond) markets, we do have control as to the methods used to accumulate funds for any given objective. These methods, when properly applied, will enable physicians to reach their goals with the minimum investment. PMID- 11771061 TI - Making it fair: how to balance schedules and compensation in a group practice. AB - Physicians prefer simplicity and would prefer to work out their differences among themselves. However, when money and personal time are at stake, a more sophisticated income distribution formula--one that prevents problems--is an excellent trade off. PMID- 11771062 TI - Financial modeling: Rx for financial success. AB - In an era of managed care, cost cutting and finding ways to increase revenue are key goals in the survival of group practices. Many practices find that they have to boost their revenue by a certain amount (for example, 20-30% within the next three years) to maintain viability in the health care marketplace. Understanding how to generate that revenue and influence short-term and long-term financial outcomes is a far trickier process. This article details how practice administrators can influence a practice's bottom line through a three-step process: (1) identify the components of the practice's financial performance and drivers of performance results, (2) diagnose the practice's current financial situation, and (3) pinpoint benchmarks and targets for success. PMID- 11771063 TI - How to steer clear of legal hassles when you fire. AB - Recent court decisions and the publicity they've gotten may explain why lawsuits from ex-employees are on the rise. However, you can keep firing from coming back to haunt you by taking several precautionary steps. In this article, the author suggests what you need to do before, during, and after you fire an employee to help prevent wrongful discharge suits. As well, the article explores steps you can take to keep unemployment benefits to a minimum. PMID- 11771064 TI - Employment practice liability: a new litigation epidemic. AB - Employment practices liability has become an increasing problem for all employers, including health care employers. This article defines the various factors that lead to employment-related claims. It also describes the legal and cultural factors that have led to the current situation and offers concrete proposals to decrease the likelihood of such claims. PMID- 11771065 TI - How to increase economic returns and reduce liability exposure: Part 1--Patient satisfaction as an economic tool. AB - This two-part article outlines a process whereby practices can enhance profitability and reduce malpractice risks. The key is involvement of all parties. First, providers at all levels, including physicians, must understand the factors that promote patient satisfaction. Next, patients must become incorporated into the diagnostic and therapeutic process. That they be allowed to do so requires a shift in providers' attitudes from one of authority figure to co manager of care. Various methods are described to help staff, providers and patients communicate better. Specific tools to increase patient involvement are outlined. PMID- 11771067 TI - New tax law makes qualified retirement plans more attractive. PMID- 11771066 TI - Recognizing and dealing with impaired clinicians: Part II--Treatment options. AB - Medical licensing boards and clinical societies encourage (and most boards require) physicians to report colleagues reasonably suspected of not practicing safely and competently. Failure to report unsafe, incompetent, or illegally acting clinicians can seriously damage patients, the profession, and the doctor himself/herself. Good-faith reporting is generally protected from lawsuit. PMID- 11771068 TI - New retirement plan designs based on new laws and regulations. AB - Retirement plan design laws have recently undergone changes that could provide significant benefits to physicians. The issues are complex, however. Effective retirement plan strategies for physicians must be crafted to align with specific goals; no clear "best choice" plan exists. This article outlines the intricacies of various funding options for retirement benefits for physicians and medical office staff. Several examples illustrate several of the permutations that are available to achieve a variety of goals. Physicians seeking to maximize benefits while minimizing economic impact should seek counsel from a competent expert on retirement plan design. PMID- 11771069 TI - Structured data entry in a workflow-enabled electronic patient record. AB - Touch-screen technology is used with a structured data entry system for electronic patient records. This article describes a program that coordinates pre set screens for detailed history, physical examination, treatment and prescription modules. It also presents "pick lists" that allow further customization and individualization of data inputs. PMID- 11771070 TI - Diagnostic decision support systems. AB - Diagnostic decision support systems are ready for prime time. We used them in a general medical clinic and found that they could suggest new diagnostic possibilities, focus thinking about clinical problems, and serve as a tool for recertification preparation. In addition, we have found diagnostic decision support systems useful for the novice clinician (fourth-year medical students and interns). These tools serve as a reminder system for learners, suggesting questions to ask the patient, physical exam components to complete, and tests to order. The novice clinician may also use these systems in preparing case presentations. The systems reviewed vary in the ways we described earlier, and there is no one "best buy." Which program is right for you depends on how much detail you want, whether you prefer a CD or internet format, and in what setting you practice. Demos are available from most vendors: Try them out, make a choice, and get on with the business of enhanced diagnostic decision making. PMID- 11771071 TI - Emerging risks of genetic testing. PMID- 11771072 TI - Home oxygen therapy. PMID- 11771073 TI - The pattern of spinal tuberculosis in Sarawak General Hospital. AB - This is a retrospective study of 53 patients with spinal tuberculosis treated in Sarawak General Hospital from 1994 until 1998. The study showed that the mean age in patients with spinal tuberculosis was 40.2 years, and was more common in male (70%) and in Iban population (50%). The clinical presentation included backache (94%); abscess (45%); neurological deficit (44%); and gibbus deformity (22%). The percentage of patient without BCG scar was 82% and 18% had evidence of pulmonary tuberculosis. The most common vertebra involved was the ninth thoracic vertebra and the least common was the third cervical vertebra. The average number of vertebra affected per patient was three. The most common radiological type of lesion was paradiscal (47%). The percentage of patients diagnosed by histological examination was 44%. All patients were given chemotherapy for 12 months' duration; 57% were treated surgically and 43% were treated conservatively. Twenty four of patients (40%) had an excellent and good results and 28 of patients had a fair result and only one patient had poor result. In 23 of patients treated conservatively showed increment of 8 degrees of kyphosis angle and 22 of patients had a fair result and only one patient had poor outcome after 6 months of treatment. In 30 of patients treated surgically showed correction of 4 degrees of kyphosis angle and 24 of them had excellent and good outcome, where 6 of them had fair outcome after 6 months of treatment. PMID- 11771074 TI - Home oxygen therapy for children with chronic lung diseases. AB - Home oxygen therapy programme is new in Malaysia. This programme enables children with respiratory insufficiency to be discharged home early. MATERIALS AND METHODS: Long term oxygen therapy was initiated using an oxygen concentrator in patients who i) remained hypoxic while breathing room air, ii) experienced desaturations of more than 20% during sleep as seen in patients with severe laryngomalacia and obstructive sleep apnoea syndrome and iii) had pulmonary hypertension with or without polycythaemia. The median with first and third quartile values are presented for the quantitative variables. RESULTS: A total of 71 patients mainly children with bronchopulmonary dysplasia (BPD) (32) and bronchiolitis obliterans (12) were discharged home on this programme. The median age at which home oxygen was initiated in children with BPD was 5.0 (Q1: 2, Q3: 8) months. The median total duration of oxygen requirement for BPD was 8.0 (Q1: 5, Q3: 12) months. The median duration of home oxygen dependency was 3.5 (Q1: 3, Q3: 6) months. However children with bronchiolitis obliterans required longer duration of oxygen therapy compared to children with BPD i.e. median duration of 28 months (Q1: 14.5, Q3: 66). In other respiratory conditions the mean duration of supplemental oxygen varies some of which may be life long. CONCLUSIONS: This paper has shown the importance of home oxygen program in children with respiratory disorders. It has significantly shortened hospital stay and thus saves hospital costs and prevents prolonged separation from the family. PMID- 11771075 TI - The effects of treating lower urinary tract symptoms on sexual function. AB - We prospectively evaluated the effect of the treatment of lower urinary tract symptoms (LUTS) on sexual function. The patients were assessed by using the International Index of Erectile Function (IIEF-15) inventory at baseline and three months after medical (alpha-blockers) or surgical treatment (transurethral resection of the prostate, TURP). Following treatment, there were improvement in erectile function and intercourse satisfaction while orgasmic, overall satisfaction and sexual drive were relatively unchanged in the medication group. Patients who had surgical treatment suffered retrograde ejaculation, dissatisfaction in sexual intercourse and overall sexual satisfaction compared to patients who were on alpha-blockers. PMID- 11771076 TI - The role of DRE in the diagnosis of prostate carcinoma. AB - DRE has been used as a diagnostic and screening tool for prostate cancer for decades. However these are based on Western data and its local applicability has yet to be verified. We held a Prostate Health Awareness Week in August 1998 and a total of 2086 men were screened. All men aged 50 years old and above were included for the study. The subjects were evaluated on DRE findings, PSA levels and if indicated a TRUS-guided biopsy results. We concluded that DRE per se might have limited role in the screening of prostate cancer in Malaysia. Screening using DRE and PSA combined are still recognized as the most cost-effective means. Neither DRE nor PSA alone has high enough specificity for diagnosis of prostate cancer cases. Combining DRE and PSA will definitely increase the specificity significantly. PMID- 11771078 TI - The prevalence of HIV positive antenatal mothers in a routine screening programme in two states. AB - This is a retrospective study of the prevalence of Human Immunodeficiency Virus (HIV) positive mothers in two states in Malaysia i.e., Perak and Negeri Sembilan since the introduction of the HIV screening programme in antenatal mothers. The study period was from 1/9/97 to 1/9/99. A total of 29 HIV positive antenatal mothers were detected (21 from Perak and 8 from Negeri Sembilan) throughout the study period. Out of the 21 HIV positive mothers from Perak, 8 (38%) were foreign nationals whereas only 1 (12%) out of the 8 from Negeri Sembilan was a foreign national. The main risk factor identified in both the groups was multiple sexual partners. The vertical transmission rates for the patients from Perak were 14.2% and 37.5% in Negeri Sembilan. There was no significant short-term adverse obstetric outcome. PMID- 11771077 TI - Swiftlase assisted CO2 laser ablation in the treatment of nasal obstruction due to hypertrophy of the inferior turbinates. AB - Hypertrophy of the inferior turbinates are the major cause of nasal obstruction. CO2 lasers have been used to reduce the size of the inferior turbinates over the last 20 years. However, the many techniques of delivery of the laser show that there is no one standard method reducing the size of the turbinates. We now describe how the laser can be applied directly to the turbinates using a handpiece with a special nasal tip, thus overcoming the disadvantages delivery via arthroscopic devices, microscopes and fibers. This technique is further enhanced by coupling it with Swiftlase which swirls the focused beam in a 3 mm spot thus ablating tissue more quickly. This procedure is done under local anaesthesia. The ablation of the anterior third of the inferior turbinates effectively overcomes nasal obstruction. This new method was compared to the more traditional submucus diathermy. 22 patients were subjected to laser treatment whilst 20 patients were subjected to diathermy. The outcome was evaluated subjectively by the patients themselves at 2 weeks, 3 months and 6 months. At the end of the study, the laser group reported a more significantly improved nasal airway (91% against 75%) and decreased rhinorrhea (72.7% against 35%) when compared to the diathermy group. PMID- 11771079 TI - Prevalence of symptomatic BPE among Malaysian men aged 50 and above attending screening during prostate health awareness campaign. AB - OBJECTIVE: To study the prevalence of symptomatic BPE among Malaysian men age 50 and above attending prostate health awareness campaign and to identify differences in prevalence between different ethnic groups residing within metropolitan Kuala Lumpur. MATERIALS AND METHODS: Demographic data and the completed International Prostate Symptom Score (IPSS), maximal uroflow rate (Qmax) and prostate size of volunteers, aged 50 and above, who attended the prostate health awareness campaign were analyzed. Subjects with known prostate diseases or prostate surgery, bladder disorders and neurological disorders were excluded. RESULTS: 2086 volunteers attended the campaign. 575 men fulfilled the inclusion criteria and their demographic data, IPSS; peak flow rate and prostate volume were analysed. Overall, 18.9% and 39.6% of the men were severely and moderately symptomatic, respectively. The prevalence of moderate to severe lower urinary tract symptoms (LUTS) in Malays, Chinese and Indians were 70%, 59% and 50% respectively (p = 0.004). The commonest bothersome symptoms were nocturia (56%), frequency (50.4%) and sense of incomplete voiding (43.5%). The mean peak flow rate of the subjects was 15.4 ml/s. 20.9% and 55.2% of the subjects had peak flow less than 10 ml/sec and 15 ml/sec respectively. The mean prostate size was 25.1 cc. There is no significant difference in term of maximal flow rate and prostate size among Malays, Chinese and Indians in Malaysia. A good correlation was found between the total symptom score and the single disease-specific quality of life question (r = 0.69, p < 0.001). The correlation between IPSS and peak flow rate (r = -0.22, p < 0.001) and prostate volume (r = 0.11, p = 0.009) was weak. There was no correlation between IPSS and age (r = 0.06, p = 0.17). The prevalence of symptomatic benign prostate enlargement (BPE) was 39.3%. The prevalence increased 8% per decade from 41.7% for men aged 50 to 59 to 65.4% for men aged 70 or more. There is no significant difference in prevalence of symptomatic BPE among the three ethnic groups. The Prevalence of BPO was 15.8%. CONCLUSION: The correlation between symptom score, maximal flow rate and prostate size was poor and one cannot predict the value of one parameter by knowing one or more of the other parameters. There is a high prevalence of LUTS suggestive of benign prostatic obstruction in the apparently healthy Malaysian aged 50 and above attending the prostate health awareness campaign. PMID- 11771080 TI - Obstruction of mechanical heart valve--diagnosis, surgical treatment and outcome. AB - From 1982 till 1999, our department performed a total of 2970 heart valve replacements--92% of which were with mechanical heart valves. During this period, there were 8 patients who came to our department with mechanical heart valve obstruction. All these patients presented with signs of heart failure or compromised haemodynamic. Confirmatory tests included transthoracic or transoesophageal echocardiography and cine fluoroscopy. Seven patients were operated upon urgently. Four of the patients had valve thrombosis. The time interval between the initial implantation and presentation varies from 4 months to 11.3 years. Six of the seven patients who were operated on recovered well from the surgery. PMID- 11771081 TI - Bacteriological study and its role in the management of open tibial fracture. AB - Sixty percent of open fracture wounds are contaminated at the time of injury. Despite that, the necessity for sequential multiple cultures and sensitivity studies for open fractures and their interpretation are still controversial. Predebridement, intraoperative, postoperative swabs and swabs in established infection for culture and sensitivity study were taken in 33 open tibial fractures over a 6 months period. 39.3% of predebridement swabs grew bacteria with the majority yielding gram-positive organism. None of the patients developed infection with similar organisms. 24.2% of the postoperative swabs grew bacteria, of which 75% were gram-negative. 50% of the patients with positive postoperative swabs developed infection. Thus, the role of sequential multiple cultures and sensitivity studies are not helpful in management of open fracture. PMID- 11771082 TI - The incidence of nosocomial infection in the Intensive Care Unit, Hospital Universiti Kebangsaan Malaysia: ICU-acquired nosocomial infection surveillance program 1998-1999. AB - CU-acquired nosocomial infection (NI) remains one of the major causes of ICU mortality. This study presents the incidence of ICU-acquired nosocomial infection in ICU HUKM for the years 1998 and 1999, as part of the ongoing ICU-acquired nosocomial infection surveillance program. The overall incidence was 23%. The main types of NI was lower respiratory tract infection (15.3%), primary bacteraemia (8.1%), ventilator associated pneumonia (5.4%), urinary tract infection (2.0%), skin infection (1.6%) central venous catheter sepsis (1.2%) and surgical skin infection (0.8%). The overall culture positive nosocomial infection rate was only 12.1%, majority from the lungs (12.6%), blood (7.3%), skin swabs (2.0%), and urine (1.6%). The main gram-negative organism cultured was Acinetobacter sp. (19%) and Staph. aureus (8.5%) was the gram-positive organism. The overall ICU mortality rate was 27.5% of which 60.9% of patients who died were attributed directly to sepsis. PMID- 11771083 TI - Dermatoglyphic analysis in Malay subjects with bipolar mood disorder. AB - Dermatoglyphic is the study of the epidermal ridges and the pattern formed by them. It may be pointed out that genetic factors have a large share in determining the variations in dermatoglyphics. It is however, suggested by evidence that bipolar mood disorder factors are determined more by genetic factors than by the environmental factors. The experiment has been undertaken to look for the effects of the bipolar mood disorder on dermatoglyphics. The dermatoglyphic characteristics of subjects with bipolar mood disorder when compared with control group revealed significant differences. The radial loop were increased in bipolar mood disorder, but there were little changes in 'atd' angles between normal and bipolar mood disorder. PMID- 11771084 TI - Mortality from congenital abnormality in Malaysia 1991-1997: the effect of economic development on death due to congenital heart disease. AB - An analysis was done of available data from the Department of Statistics Malaysia, on the type of congenital abnormality contributing to death, to determine whether progress in health care over recent years was associated with any decline in mortality from congenital abnormality. A significant decline in death due to congenital abnormality was observed between 1991 and 1996. This was attributable to a decline in deaths due to congenital heart disease occurring because of improvements in cardiac surgical services for infants. In 1997 death due to congenital heart disease increased significantly. This could be attributed to improvements in the diagnosis of congenital heart disease in the neonate. PMID- 11771085 TI - Hyponatraemia in hospitalised elderly patients. AB - This study aims to investigate the incidence and causes of hyponatraemia in hospitalised elderly patients. There was a total of 407 new patients. 55 (13.5%) patients were found to have at least one episode of hyponatraemia during their hospitalization. There were 58 deaths. Fifteen out of 55 (27.3%) patients who had hyponatraemia died compared to 43 out of 352 (12.2%) normonatraemic patients (chi square significant, p < 0.01). The three most common causes of hyponatraemia were syndrome of inappropriate antidiuretic hormone secretion (SIADH), poor oral intake and diuretics. The two most common causes of SIADH were lower respiratory tract infection and stroke. PMID- 11771086 TI - The trans-septal approach to the mitral valve. AB - To assess the efficacy of the trans-septal approach to the mitral valve, 40 patients who underwent mitral valve surgery via this approach were compared to 37 patients who underwent surgery via the standard left atriotomy. Concomitant procedures included tricuspid annuloplasty, aortic valve replacement, closure of atrial septal defect, coronary artery bypass grafting and aortic valve repair. There was one (1.2%) operative mortality. No patients required pacemaker implantation. Follow-up of up to 18 months showed that all patients were in NYHA classes I and II. One third of the patients who had trans-septal approach to the mitral valve achieved conversion from atrial fibrillation to sinus rhythm while none of the patients who underwent conventional left atriotomy had conversion (p < 0.02). The trans-septal approach to the mitral valve is a useful approach in selective patients requiring mitral valve surgery. PMID- 11771087 TI - Mortality in the Department of Surgery, Alor Setar Hospital. AB - This is a retrospective study of the annual mortality that occurred in the Department of Surgery, Alor Setar Hospital, for the years 1995 to 1997. This study looks at the number of admissions to the surgical wards and categorizes the causes of death. The annual mortality rates were 2.60, 2.89 and 3.25 per hundred admissions for the year 1995, 1996 and 1997 respectively. Head injury was the leading cause of death whilst sepsis and advanced malignancies second and third commonest causes. We hope that with the publication of these figures, we can initiate more studies to analyse similar local data. PMID- 11771088 TI - Chronic hepatitis C--a study of 105 cases between 1990-2000. AB - An analysis of 105 consecutive patients with chronic hepatitis C at the gastroenterology outpatient's clinic in Hospital Kuala Lumpur was performed. The clinical, laboratory and virological data was prospectively recorded in the case notes and comprised of data on patient characteristics, risk factors, clinical features, laboratory features, virology screen and management. Chronic Hepatitis C cases accounted for 2.1% of the total number of cases seen at this clinic during the entire period. There were 78 (74%) males and 27 (26%) females. The ethnic breakdown consisted of Chinese (44.2%), Malays (39.4%), Indians (15.4%) and others (1%). There was higher male preponderance in all the ethnic groups. The main mode of transmission was blood transfusion comprising 51 patients (48.8%). A total of 35.2% of cases underwent treatment, of which a proportion had interferon monotherapy for 6 or 12 months and a subsequent group of naive patients and non-responders underwent combination therapy with interferon and ribavarin. PMID- 11771089 TI - Partial resection of pelvis and salvage of the lower limb in the treatment of malignant pelvic tumours. AB - Malignant pelvic tumours often present late, hence a high index of suspicion should be maintain in order to arrive at the diagnosis. This is particularly true for those who have unusual symptoms. A proper planning and staging strategies is required to save the limb, and the limb salvage surgery is at present the surgery of choice to achieve local control and restoring optimum functions of the lower limbs as being illustrated by our three cases. PMID- 11771090 TI - Ocular fishhook injuries. AB - Ocular fishhook injuries are rare, yet potentially vision threatening as complications such as corneal scarring, retinal detachment and endophthalmitis may result. The surgical management of these cases is challenging due to the construction of barbed fishhooks. PMID- 11771091 TI - Adenocarcinoma of rectum metastasizing to penis. AB - An elderly gentleman with adenocarcinoma of the rectum who had abdominoperineal resection presented with scrotal skin and penile metastasis. Adenocarcinoma of the rectum metastasizing to the groin and penis is very rare and few cases have been reported. PMID- 11771092 TI - Is there a lack of awareness of percutaneous endoscopic gastrostomy (PEG) amongst local non-gastrointestinal specialists?--experience with PEG in a Malaysian hospital. PMID- 11771093 TI - The management of upper respiratory tract infections. AB - Upper respiratory tract infections are the commonest reason for consultation in primary care. Group A beta-haemolytic Streptococcus (GABHS), the most important bacterial pathogen in this condition, can be cultured from about 30% of patients, more so in children than adults. Clinical features that are predictive of positive GABHS culture are absence of cough, fever, cervical adenopathy, tonsillar enlargement and tonsillar exudate. Use of a sore throat score can help in the detection of streptococcal throat infection. Symptomatic therapies which are useful include anticholinergic, antihistamine, decongestant, humified hot air and Vitamin C. Antibiotics are universally over-prescribed in this condition as a result of high patient expectation and faulty clinical decision making. Oral Penicillin V for 10 days is the drug of choice. Effective intervention to reduce inappropriate antibiotic prescription probably require a multifaceted approach targeted at both the patients and the prescribers. PMID- 11771094 TI - [The price of success - informatics in ophthalmology]. AB - Medicine and engineering seemed to be until now two so different field that have nothing in common. By the present, we have tried to show, how to make your work easier and perform, being helped by an application named OPTILINK, which combine so successfully those two fields. Also, in this paper work we have presented the way this application work and all the apparatus you need for. OPTILINK means working directly with an application engineer who not only understand your needs, but can also help you specify affordable opto-mechanical components to meet those needs. PMID- 11771095 TI - [Color Doppler echography in oculo-orbital diseases]. AB - The orbital color Doppler echography introduces in imaging arsenal, an information about perfusion of parenchymatous organs and vessels, associated to B scan sonography. The visualisation of orbital vasculature, has opened a new dimension in ophthalmological US exploration, with applications in normal ocular vasculature evaluation, and also, in regional pathological field: tumor, ocular vascular malformations, carotid-cavernous fistulas, central retinal artery and vein occlusion, ischaemic pathology of the optic nerve, micro/macro diabetic angiopathy, the evaluation of diagnosis and therapy in open-angle glaucoma. Adding the power-angio exploration system, combined with dye injection, may increase the vascular informations in the field of oculo-orbital tumoral pathology. A good knowledge of the anatomy and the pathology, as well as, a high experience in Echo-Doppler examination, are considered as fundamentals in a successful approach of this new exploration method. PMID- 11771096 TI - [Open angle glaucoma and pigmentary epithelial iris tumor]. AB - The authors present a case of a 60 years old patient which is under a 6 years treatment already for open angle glaucoma. In addition the patient present pigmentary epithelial iris tumor. PMID- 11771097 TI - [Orbital tuberculoma]. AB - We present a case of orbital tumor with skin lesions at the lateral cantus. CT scan confirmed the orbital tumor and we considered it to be malignant. The histological examination of a piece of the tumor showed tuberculous characteristics. Patient received treatment with antituberculous drugs and steroids. The tumor decreased after two months of treatment. PMID- 11771098 TI - [A peculiar case of microcystic macular edema]. AB - We present a case of microcytic macular oedema, in a patient 60 years old, suffering of systemic lupus erythematosus. The specific feature of the case is the presence of the microcystic macular oedema, as the only form of manifestation of the retinal lesions in the posterior pole. The diagnosis, etiopathogenicity and treatment are discussed. PMID- 11771099 TI - [Temporal arteritis with giant cells]. AB - Giant cell (temporal) arteritis remains an enigmatic but a very serious systemic vasculitis which can lead to total, irreversible blindness if not diagnosed and treated swiftly. The characteristic granulomatous inflammation of the vessel wall of large and medium-sized arteries is present. To maintain high standards of management, ophthalmologists need to be aware of the clinical available diagnostic tests and treatment strategies. Corticosteroids remain the treatment of choice. PMID- 11771100 TI - [Fuchs's syndrome or Eales's disease ?]. AB - The authors report a female patient case presenting anterior signs of Fuchs' Syndrome (iris heterochromic, keratitis precipitates) as well as signs of Eales' Disease (proliferative retinopathy, peri-vasculitis). PMID- 11771101 TI - [Acute posterior or multifocal placoid pigment epitheliopathy]. AB - The paper presents a clinical case of Acute Posterior Multifocal Placoid Pigment Epitheliopathy and the specific diagnosis problems of this case. Being a less frequent disease the common aspects are emphasized as well as the latest concepts about this syndrome. PMID- 11771102 TI - [Glucocorticoids in ophthalmology- therapeutic value and strategies of rational utilization]. AB - This paper presents the most used glucocorticoids in the ophthalmic treatment, topic, periocular and systemic administrations, as well as the indications, contraindications and complications of this therapy. PMID- 11771103 TI - [Surgical principles and techniques in severe proliferative diabetic retinopathy]. AB - The development and new achievements of the last 30 years in vitreo-retinal surgery, since Machemer developed pars plana vitrectomy as surgical treatment of diabetic retinopathy, have led to a marked change of indications as well as surgical techniques which are applied in this disease. Surgical indications in severe proliferative diabetic retinopathy are: severe vitreous hemorrhage, tractional retinal detachment recently involving the macula, combined tractional and regmatogenous retinal detachment, severe fibrovascular proliferation, premacular dense hemorrhage, chronic macular edema, hemolytic glaucoma and anterior segment neovascularization with media opacity. PMID- 11771104 TI - [Electrical changes in the external retinal layer in the course of diabetic retinopathy (Electroretinographic study)]. AB - An electroretinographic study was undertaken on 27 diabetic subjects, in order to catch the modifications arose in the external retinal layer, that means at the photoreceptor level, in ischaemic conditions. As expected, the parameters of the a wave were significantly modified by the progression of diabetic retinopathy. Cones and rods showed a different response to ischaemia. PMID- 11771105 TI - [Oculo-orbital manifestations of paranasal sinus diseases]. AB - PURPOSE: The paper is a study of the oculo-orbital affections established by the sinusal lesions. METHODS: The study is retrospective for five years and it is affected by the patients with ocular and orbital affections hospitalized in Ophthalmological Clinic. Were used the sheets of the patients and a collaboration with ORL Clinica, where the sinusal affections were surgical cured. RESULTS: The ocular lesions caused by the sinusal inflammations were: acute uveitis, orbital cellulitis, unilateral exophthalmia without obvious inflammatory signs. The oculo orbital signs were missing with oculo/sinusal treatment. CONCLUSIONS: Without treatment, the inflammatory or tumoral affections of the paranasal sinus, established oculo-orbital complications and the patients request the first time the oculist. It is necessary a collaboration between the ORL--ist and the oculist physician for of these cases. PMID- 11771106 TI - [Inflammatory ocular diseases associated with oro-dental pathology]. AB - PAPER AIM: It is presented the correlation between the uveitis and the focal dental disease with infection, irritation or allergic pathogenicity. MATERIAL AND METHOD: This study was performed on a set of 54 patients with uveitis and dental diseases patients hospitalized in the Clinic of Ophthalmology of Craiova, during 1998-1999. This correlation was observed in 38-40% of uveitis. There were also mentioned some dental damages associated with uveitis: radicular focal infections, periodontitis under prosthetic works, fights cavities, inclusions dental chronic maxillary osteitis. RESULTS: The correlation uveitis-dental diseases was noticed in 1.2-1.8% of the hospitalized patients, comparing with 3 5% in literature (including the ocular adnexa diseases). CONCLUSIONS: This study shows the reality of the correlations between uveitis and dental diseases. It was relieved the importance of correlation ophthalmologist-stomatologist. PMID- 11771107 TI - [Serpiginous choroiditis - clinical study]. AB - The work shows a retrospective study a period of 12 years, on a number of 34 cases of serpiginous choroiditis. The average age of the patients was 36 years (29-68). The start of the illness was juxtapapillary in 99.1% and macular on 5.9% of the cases. The bilateralism was present in all the cases (delayed start), and the visual acuity was strongly affected in macular localizations. The ophthalmoscopical and angiofluorographic aspect is specific for all the evolutive phases, and the extension of the lesions is made by means of pseudopodia. problems of differential diagnosis, pathogenesis (hereditary, inflammatory, vascular) are discussed. We have obtained satisfying results by triple association of immunosuppressants: azathioprine, cyclosporins and prednisone. PMID- 11771108 TI - [Evaluation of efficacy and safety of sterile solution of lodoxamide in patients with ocular allergy]. AB - PURPOSE: Evaluating the efficiency and safety of Alomide (lodoxamide 01.%) in the treatment of allergic conjunctivitis. MATERIAL, METHOD: 12 patients have been selected during may-august 1998, in order to be treated with Alomide 4 times daily. The clinical exam of the patient included: general information, history, ocular examination. The ocular status of each patient has been evaluated with a score: the intensity of each symptom and sign has been graded between 1-3. RESULTS: In all cases, the use of Alomide induced the improvement of the typical symptoms and signs of the allergic conjunctivitis. No side effect related to the use of the drug has been noted. CONCLUSION: Due to its dual action (inhibition of both mast cells and eosinophils), Alomide covers most of the allergic response. PMID- 11771109 TI - [Incidence of ocular trauma in Clinical Hospital Oradea between 1997-1999]. AB - The purpose of the study is to analyse the great number of ocular injuries which were diagnosed and treated in the out-patients clinic or in the hospital in 1997 1999. Ocular trauma seems to be related to the working place or the main activities of the patients, such as agriculture or housekeeping. Ocular injuries in children are significant as number and prognosis. Blunt trauma, ocular perforations, ocular foreign bodies and burns were studied separately for children, housekeepers, unemployed, working and retired people. Due to their number and complexity, ocular trauma represent a very important part in the activity of an ophthalmology department. The conclusion of the study is the number of ocular injuries decreased over the years because of the reduced industrial activity in our town. Similar ocular injuries in retired and working people suggest that retired people are still active. The prognosis of ocular trauma is better if the patients come early to be seen by the specialist, if the treatment is adequate and if the department has a proper equipment for advanced surgery techniques. PMID- 11771110 TI - [Ocular myopathies - cause of exophthalmia]. AB - It presents the "thickenings" of the extraocular muscles that can cause exophthalmos. It makes the difference between myositis limited to the orbit and the systemic myopathies and endocrine myopathies. PMID- 11771111 TI - [Polychlorinated biphenyls--toxicology and health risk]. AB - Polychlorinated biphenyls (PCBs) were or are manufactured as commercial products. The chemical stability and lipophilicity of these compounds, and their resistance to degradation results in their persistence in the environment and bioaccumulation in animal organisms by entering of various food chains. Food, especially of animal origin, is regarded as a major source of these chemicals for man. Acute toxicity of PCB is low. However, when absorbed in low doses over longer time periods they can cause changes leading in chloracne and other hypo- and hyperplastic responses, endocrine disorders, hepatotoxicity and porphyria, reproductive toxicity and carcinogenesis. Infants fed with breast milk are at greatest risk. The health risk assessment for environmental exposure to PCB was also discussed. PMID- 11771112 TI - [Phytoestrogens in food--a review]. AB - The steroid hormone estrogen influences female and male reproductive system, 17 beta-oestradiol is the major human oestrogen. Phytoestrogens are naturally occurring oestrogens in many foods of plant origin. They are structurally and functionally similar to 17-beta-oestradiol or produce estrogenic effects. It is suggested that phytoestrogens could lower risk of diseases accompanied woman in meno- and postmenopausal stage. They are consider to decrease risk of breast, endometrial and ovarian cancer, osteoporosis, cardiovascular disease. This report presents the literature review on nutritious and health aspects connected with phytoestrogens. Generally authors confirm the possibility of beneficial health effects of phytoestrogens in humans. PMID- 11771113 TI - Effects of oral coenzyme Q10 supplementation on sodium nitrite-induced lipid peroxidation in rats. AB - Studies were carried out to examine the anti-oxidative effect(s) of oral coenzyme Q10 supplementation (10 mg/kg b.w./day) in rats treated per os with either sodium nitrite (10 mg/kg b.w./day) or saline (control) for 14 days. Results showed that sodium nitrite increases thiobarbituric-acid reactive substances (TBARS in rat small intestinal mucosa and liver, and the agent did not have any effect(s) on the total anti-oxidant status (TAS) and lipid peroxidation of rat blood. Pretreatment of nitrite-poisoned rats with coenzyme Q10 mitigated TBARS and increased TAS in animal blood. Coenzyme Q10 has been found to be a promising anti oxidant agent in sodium nitrite-induced lipid peroxidation. PMID- 11771115 TI - [Bioavailable fluoride in poultry deboned meat and meat products]. AB - Deboned poultry meat (MDOM) consists of meat and fat and may also contain pieces of bones. This type of meat is a raw material used for production of different kinds of sausages. The aim of our investigation was to determine whether MDOM could be the significant source of bioavailable fluorine. Sample of MDOM and poultry meat products were digested in 37 degrees C water bath shaker with pepsin and 0.1 M HCl and then neutralized by adding carbonate and digested with pancreatine. Measurement was performed by ionoselective fluoride electrode. Fluorine determined in prepared samples is potentially ready to be absorbed by organism. Nine kinds of MDOM and eight poultry meat products were investigated. Content of fluorine in MDOM ranged 0.3-2.7 mg/kg of fresh weight but in one sample of turkey meat--7.4 mg/kg, while determined content of fluorine in poultry meat was low--not exceeded 0.2 mg/kg. Sausages prepared from homogenated meat contained fluorine from 0.5 to 0.7 mg/kg. In products prepared from big pieces of meat the content of fluorine was lower. CONCLUSIONS: MDOM is characterized by higher level of bioavailable fluorine than muscle tissue. MDOM in poultry meat products may be a source of higher fluoride content. PMID- 11771114 TI - [The determination of Cu, Cd, Pb, Co and Ni in material with the use of the ICB AES method]. AB - The purpose of the study was utilization of emission atomic absorption spectrometry with excitation in induction-coupled plasma for determination of Cu(II), Pb(II), Cd(II), Co(II) i Ni(II) in plant material. The possibility of using inorganic carrier for separation of trace amounts of heavy metals from aqueous solution is presented. Optimal conditions for coprecipitation of metal ions with Mg(OH)2 as well as for their determination by means of the ICP-AES method are described. The conditions of heavy metals separation and concentration make possible determination of the metals in the concentration from 0.01 to 0.20 microgram/ml by the ICP-AES. As a result simple method was elaborated for group concentration and determination of the above mentioned metals in samples of plant material. The studied food products were mineralized with concentrated HNO3, HClO4 and perhydrol. The method of preconcentration and determination was used for metals determination in dairy products in concentrations about 5 x 10(-5)%. As a result simple and economical method was elaborated for group preconcentration and determination of the above mentioned metals in samples of plant material. PMID- 11771116 TI - [Nitrate and nitrite content in potatoes from ecological and conventional farms]. AB - The aim of this investigation was to determine nitrate and nitrite content in potatoes from ecological and conventional farms. The influence of variety on nitrate and nitrite content was also evaluated. Vegetables and potatoes from ecological cultures are supposed to contain less nitrates and nitrites and on this basis could have been advised for children, sick and people in special physiological stages. Nitrite content was determined colorimetrically, with sulfanilic acid, nitrate content was determined following reduction of nitrites by means of metallic cadmium. The results showed significantly lower nitrate content in potatoes from ecological farms, and almost twice higher in those from conventional farms. The nitrite content showed no differentiation in conventional and ecological farms. Within three varieties of potatoes (sokol, bryza, ania) significantly highest content of nitrate was determined in bryza. Considering low nitrate level potatoes from ecological farms could be advised for children and sick people, but for the complete safety evaluation also content of other contaminants (i.e. heavy metals) have to be assessed. PMID- 11771117 TI - [Radon 222 in drinking water from Jelenia Gora area]. AB - In the last decade one can observe an increasing interest in the study of 222Rn levels in water samples. In Poland, radon concentration is measured continuously and routinely only in mineral and medical waters from springs located in the area of health resorts in the Sudety Mountains. The reason for these studies is the fact that waters present in this area have a high radon concentration. Radon--222 concentration in surface water, wells water and tap water in Jelenia Gora has been quantitative determined. The measurements were performed using the alpha liquid scintillation counting method. "Grabarow", the main waterworks in Jelenia Gora is supplied with the mixed water consisting from the surface water (river Bobr), which main characteristic is low radon concentration (below 11 Bq/l), and from ground water with the radon concentration from 179.6 Bq/l to 289.0 Bq/l in it. Also, waterworks "Ceglana", "Pod Karpaczem", "Sniezne Kotly" is supplied with the ground water have a high radon concentration: from 93.2 Bq/l to 216.4 Bq/l. The next waterworks: "Podgorzyn", "Lesniczowka", "Kamienna Wieza", "Gorzyniec" and "Centrum-Jelchem" is supplied with the surface water in which the radon concentration is low: from 1.1 Bq/l to 7.5 Bq/l. The annual effective dose to an individual from an intake of radon-222 via ingestion of drinking water is calculated by the Crawford-Brown's biokinetic model. In the present study it was found to be about 0.9 mSv/y (222Rn concentration level in drinking waters about 200 Bq/l). PMID- 11771118 TI - [Evaluation of protein, fat and carbohydrate contents in daily dietary allowance of overweight and obese students from the Medical Academy in Bialystok]. AB - The major causes of primary obesity include dietary errors (e.g. high-fat, high energy diets) and low physical activity. Therefore, the aim of the present study was the quantitative evaluation of daily dietary allowances of students with overweight and obesity in the Medical Academy of Bialystok. Questionnaire investigations were conducted in the years 1997-1999 and included 1050 students (701 women and 349 men). Basing on BMI overweight was revealed in 22 women (3.14%) and 82 men (23.5%). Obesity was found in only 2 women (0.3%) and 4 men (1.2%). The 24-hour dietary history of the preceding day was the method used for quantitative analysis. Low physical activity and low-energy food intake (below the recommended safe norm) were the characteristic features found in the majority of students with overweight or obesity. Their daily dietary allowances showed high protein content (above the safe norm in 75% of women and 87.2% of men) and low content of carbohydrates (below the safe norm in over 70% of those examined). Fat content above the safe norm was found in approximately 55% of men with overweight and obesity, the rest consumed low-fat foods. The incidence of overweight or obesity was higher in young men than women studying in the Medical Academy of Bialystok. In some of them, this may be caused by a disturbed proportion in the consumption of the major food components (protein, fat, carbohydrates). PMID- 11771119 TI - [Supervision of cosmetic products]. AB - In connection with adaptation of Polish law to UE regulations, there were presented rules of supervision organisation over cosmetic products in Poland and supervision in selected Member States. There were also shown problems, that appear the most often during supervision. Present day, in Poland supervision over cosmetics is made in two-stage way. There is the pre-market control--registration products in National Institute of Hygiene (PZH) and in the market control conducted by the sanitary-epidemiological stations. In UE countries only in market control exists. There were also defined rules of supervision in Poland, after putting Act on Cosmetics into force. Due to, on the basic on Directive 76/768/EEC there were prepared lists: the substances forbidden to be used in cosmetics, permitted to be used in cosmetics only with restrictions, allowed colouring agents, preservatives and UV filters. These lists will be included in Act on Cosmetics, as regulation. PMID- 11771120 TI - Intermolecular forces in biology. PMID- 11771121 TI - Nevada Supreme Court wrestles with HCQIA immunity. Meyer v. Sunrise Hospital. PMID- 11771122 TI - Dealing with the apparently impaired patient. Thomas v. Deitsch. PMID- 11771123 TI - [Computer analysis of regulatory signals in bacterial genomes. Fnr binding segments]. AB - Comparative approach to computer analysis of regulatory signals allows one to predict new signals in bacterial genomes with high accuracy. A prediction is reliable whenever candidate signals are consistently observed in several related genomes. We applied comparative approach to the analysis of the Fnr regulon of gamma-proteobacteria. Responding to changes in the aerobic/anaerobic state of the medium, the transcriptional factor Fnr regulates expression of many genes. We predicted Fnr binding-sites in 12 genes regulated by Fnr, and identified 17 new operons as potential members of the Fnr regulon of Escherichia coli. In addition, we described the Fnr regulon of other gamma-proteobacteria. PMID- 11771124 TI - [Study on regulation of long-chain fatty acid metabolism with the use of computer analysis of complete bacterial genomes]. AB - One of the main trends in the prokaryote genomics is the comparative analysis of metabolic pathways. This method can be used for the analysis of experimentally studied systems of co-regulated genes, as well as genes with unknown regulatory signals. In this study we apply the comparative analysis of regulatory signals to the genes of the enzymes for fatty acid metabolism from Escherichia coli, Haemophilus influenzae, Vibrio cholerae, Yersinia pestis. Transcription of these genes is regulated by the FadR protein. We describe the FadR regulation of the long-chain fatty acid oxidation and partially that of the fatty acid biosynthesis. We also demonstrate that the gene yafH encoding acyl-CoA dehydrogenase is identical to the gene fadE, previously identified by genetic techniques. PMID- 11771125 TI - [A rapid method for detecting interconnections between functionally and/or evolutionary close biological sequences]. AB - It is now common practice to retrieve, by key words, highly specialized selections of sequences from general-purpose databases such as EMBL, GenBank, etc. The sequences included in a selection are often interconnected, which means that there are duplications, embeddings, intersections, homology, common structural elements. Knowledge of these interconnections is necessary for further processing of the sequences. We propose a rapid (single scan) method for identification of such interconnections by means of complexity analysis that generalizes the Lempel-Ziv approach. Analysis of a selection of 5'-flanking regions of vertebrate growth hormone genes from EMBL is presented as an example. PMID- 11771126 TI - [Evolution of MIR-repeats in coding regions of the human genome]. AB - A search for new members of the mammalian interspersed repeat (MIR) family has been done over the coding regions of human genome from GenBank-116. Only 254 nucleotide sequences contained MIRs in coding regions, of which 45 MIR copies were unknown before, including 17 that occurred in translated gene regions. The program developed by the authors has been demonstrated to surpass the CENSOR program in the search power. The evolution of the MIR copies located in translated regions of human genome is discussed. PMID- 11771127 TI - [Structural organization of the human genome: distribution of nucleotides, Alu repeats and exons in chromosomes 21 and 22]. AB - Analysis of DNA sequences of the human chromosomes 21 and 22 performed using a specially designed MegaGene software allowed us to obtain the following results. Purine and pyrimidine nucleotide residues are unevenly distributed along both chromosomes, displaying maxima and minima (Y waves phi) with a period of about 3 Mbp. Distribution of G + C along both chromosomes has no distinct maxima and minima, however, chromosome 21 contains considerably less G + C than chromosome 22. Both exons and Alu repeats are unevenly distributed along chromosome 21: they are scarce in its left part and abundant in the right part, while MIR elements are quite monotonously spread along this chromosome. The Alu repeats show a wave like distribution pattern similar for both repeat orientations. The number of the Alu repeats of opposite orientations was equal for both studied chromosomes, and this may be considered a new property of the human genome. The positive correlation between the exon and Alu distribution patterns along the chromosome, the concurrent distribution of Alu repeats in both orientations along the chromosome, and the equal copy numbers for Alu in direct and inverted orientations within an individual chromosome point to their important role in the human genome, and do not fit the notion that Alu repeats belong to parasitic (junk) DNA. PMID- 11771128 TI - [mRNA-FAST (mRNA-Function, Activity, STructure) computer system]. AB - Computer system mRNA-FAST (mRNA--Function, Activity, STructure; http://wwwmgs.bionet.nsc.ru/mgs/dbases/trsig/) is described. The system has been developed to analyze nucleotide sequences of mRNA and to measure their essential properties. The system compiles the data base on translation signals including nucleotide sequences of the regulatory regions with structural and experimental information on their specific activities. It also contains programs to search for local homology between mRNA and translation signals, to search for potential signals basing on analysis of the oligonucleotide dictionaries, and to model secondary RNA structure. Possible applications of the system mRNA-FAST are discussed. PMID- 11771130 TI - [Analysis of structural motifs of proteins using sets of codes, describing local structures]. AB - An amino acid sequence pattern conserved among a family of proteins is called motif. It is usually related to the specific function of the family. On the other hand, functions of proteins are achieved by their 3D structures. Specific local structures, called structural motifs, are considered related to their functions. However, searching for common structural motifs in different proteins is much more difficult than for common sequence motifs. We are attempting in this study to convert the information about the structural motifs into a set of one dimensional digital strings, i.e., a set of codes, to compare them more easily by computer and to investigate their relationship to functions more quantitatively. By applying the Delaunay tessellation to a 3D structure of a protein, we can assign each local structure to a unique code that is defined so as to reflect its structural feature. Since a structural motif is defined as a set of the local structures in this paper, the structural motif is represented by a set of the codes. In order to examine the ability of the set of the codes to distinguish differences among the sets of local structures with a given PROSITE pattern that contain both true and false positives, we clustered them by introducing a similarity measure among the set of the codes. The obtained clustering shows a good agreement with other results by direct structural comparison methods such as a superposition method. The structural motifs in homologous proteins are also properly clustered according to their sources. These results suggest that the structural motifs can be well characterized by these sets of the codes, and that the method can be utilized in comparing structural motifs and relating them with function. PMID- 11771129 TI - [Properties of artificial evolution of proteins and peptides]. AB - In vitro evolution is used to study protein sequences, structures, and interactions and to obtain proteins with new properties. To analyze the specific features of this process in experiments with phage display, we studied the amino acid composition of selected sequences, constructed a matrix of amino acid substitutions, and identified pairs of coadaptive substitutions. Amino acid frequency proved to be tightly associated with the number of corresponding codons; numerous correlated substitutions were found. PMID- 11771131 TI - [Apoptosis and response to heat shock of interference gene networks]. AB - Experimental data on the function and the regulation of stress-response gene networks are integrated in the GeneNet database (http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/). Section Heat Shock Response contains data on the genes that are expressed in a coordinated manner in response to heat shock. Data of section Thermotolerance testify to the role of heat-shock proteins in suppressing apoptosis and in determining thermotolerance. The information on transcription regulation, regulatory regions, and transcription factor-binding sites is accumulated in TRRD (http://www.bionet.nsc.ru/trrd/), section Heat Shock-Induced Genes (HS-TRRD). PMID- 11771132 TI - [A generalized chemical-kinetic method for modeling gene networks]. AB - Development of methods for mathematical simulation of biological systems and building specific simulations is an important trend of bioinformatics development. Here we describe the method of generalized chemokinetic simulation generating flexible and adequate simulations of various biological systems. Adequate simulations of complex nonlinear gene networks--control system of cholesterol by synthesis in the cell and erythrocyte differentiation and maturation--are given as the examples. The simulations were expressed in terms of unit processes--biochemical reactions. Optimal sets of parameters were determined and the systems were numerically simulated under various conditions. The simulations allow us to study possible functional conditions of these gene networks, calculate consequences of mutations, and define optimal strategies for their correction including therapeutic ones. Graphical user interface for these simulations is available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneNet/. PMID- 11771133 TI - [On connection of a graph of a gene network with qualitative modes of function]. AB - Theoretical investigation of properties of assumed gene networks constructed from elementary units of two types, genetic elements and control links, was carried out. A test was formulated for a subclass of such networks with cyclic structure called S(n,k)-networks allowing calculation-free prediction of the network limiting properties (the presence/absence and number of stationery and/or cyclic functioning modes) from a graph of the network structure. The obtained data can be useful for constructing gene networks with predefined properties. PMID- 11771134 TI - [Modeling real eukaryotic control gene subnetworks based on generalized threshold models]. AB - Mathematical and computational means are developed that take into consideration the specifics of control processes at the molecular level and allow one to obtain both qualitative and quantitative patterns of gene network dynamics. Using the method of generalized threshold models, models are constructed for the Arabidopsis thaliana flower morphogenesis control subsystem and gene subnetwork controlling the Drosophila melanogaster early ontogeny. The dynamics of these systems are investigated: kinetic curves are computed for molecular components (RNA, proteins), possible modes of functioning and steady states of the nets are revealed and biologically interpreted. The models are shown to be adequate to the real processes. The effectiveness of the generalized threshold model method is evaluated in the analysis of the actual eukaryotic gene networks. PMID- 11771135 TI - [Kinetic modeling of energy metabolism and generation of active forms of oxygen in hepatocyte mitochondria]. AB - Direct nonenzymatic oxidation of semiquinone by oxygen is one of the main sources of superoxide radicals (O2.-) in mitochondria. By using all the known data on hepatocyte mitochondria, we have revealed the correlation between the rate of superoxide generation by the bc1 complex and the transmembrane potential (delta psi). If the main electrogenic stage of the Q cycle is suggested to be the electron transfer between the cytochrome b hemes, then the rate of superoxide generation sharply increases when delta psi grows from 150 mV to 180 mV. However, this interrelation is ambiguous. Indeed, the increase of the generation rate with the growth of the potential can occur faster when succinate dehydrogenase is inhibited by malonate than when external ADP is exhausted. When the potential is changed by adding phosphate or potassium (K+), the rate of O2.- production remains constant, although the comparison of the rate values at the same delta psi reveals the effect of phosphate or potassium. It turned out that the rate of O2.- generation is a function of delta mu H rather than any of its components. Phosphate and K+ have practically no influence on delta mu H, since the change in delta psi is compensated by delta pH. The rate of superoxide generation by the bc1 complex is a multiple function of the electron-transfer activity of enzymes, the processes determining the membrane potential (e.g., loading), and of the oxygen concentration. The kinetic model proposed in this work may serve a tool to understand how the superoxide production is regulated. PMID- 11771136 TI - [Revealing key interactions in the metabolic network: a model of primary phosphate transport in bacteria]. AB - One of the main problems of metabolic engineering is to determine the genetically controlled limiting links of a metabolic network. We have built a model of the primary transport of inorganic phosphates (Pi), analyzed the Pi metabolic network in Gram-negative bacteria, and determined the factors controlling the phosphate exchange. The model explains why the Pi primary transport is not observed at the release stage. The nonlinearity of primary transport and the differences in its parameters in the membrane and within the cell give rise to transport asymmetry, i.e., the Pi release rate is low as compared with the uptake rate, and is small at the background of secondary transport. Discussed is a general scheme of coordination between primary and secondary transport, which are interconnected through the substrate-product reration. PMID- 11771137 TI - [Spatial registration of data on gene expression in situ]. AB - For registering data on the in situ expression of segmentation genes, a method of image registration was developed basing on the spline approximation. The reference points for the registration were the coordinates of extrema in one dimensional patterns of gene expression. This registration method is characterized by a very high accuracy. A method of creating a generalized pattern of gene expression in single cells is proposed. Such patterns were constructed for nine segmentation genes belonging to the gap and pair-rule classes of genes. PMID- 11771138 TI - [A review of resources of the Internet site "Practical Molecular Biology"]. AB - In 2000, in the middle of September, the Russian Web site Practical Molecular Biology (http://molbiol.edu.ru) was opened. The main tasks of the project are (i) distribution of experimental work experience among Russian and foreign laboratories, and (ii) organization of an information database in Russian for researchers connected with molecular biology or medicine. PMID- 11771139 TI - [Bioinformatics of genomic regulation and structure]. PMID- 11771140 TI - [Regulation of eukaryotic gene transcription: description in the TRRD database]. AB - The structure of the Transcription Regulatory Regions Database (TRRD) and the principles of considering transcription regulation of eukaryotic genes in TRRD are concerned. Formal description of the structural and functional organization of the regulatory gene regions is illustrated with examples. By now, TRRD is based on 3500 original works and contains data on transcription regulation of more than 1100 genes known to possess more than 5000 transcription factor-binding sites and about 1600 regulatory elements (promoters, enhancers, silencers). TRRD is available at http://www.bionet.nsc.ru/trrd/. PMID- 11771141 TI - [Locus-controlling regions: description in the LCR-TRRD data base]. AB - The structural and functional organization of locus control regions (LCR) was analyzed using data of the LCR-TRR Database. The role of several transcription factors in the LCR function was considered. A study was made of the possible nucleosomal packing of enhancer regions in LCR. The structure and the format of LCR-TRRD are described. The database has been constructed for SRS and is available at http://wwwmgs.bionet.nsc.ru/mgs/dbase/LCR/. PMID- 11771142 TI - [Computer system "Gene Discovery" for searching for regularities in organization of eukaryotic regulatory sequences]. AB - A method is proposed to automatically search for patterns in the mutual location of context signals in regulatory DNA sequences. The procedure is based on the methods of Data Mining and Knowledge Discovery software, implemented in a computer system Gene Discovery. This system was used to study erythroid-specific promoters and promoters of the endocrine-system genes from TRRD. We detected some trends in occurrence and localization of specific oligonucleotide groups. PMID- 11771143 TI - [Comparative analysis of methods for recognizing potential transcription factor binding sites]. AB - A complex approach to recognize transcription factor binding sites (TFBS) has been developed based on four methods: (i) weight matrix, (ii) information content, (iii) multidimensional alignment, and (iv) pairwise alignment with the most similar representative of known sites. It has been shown that no method optimal for all kinds of sites occurs among the considered methods, so in each case, the appropriate way of recognition should be chosen. The approach proposed allows one to minimize the errors of TFBS recognition. The program available through the Internet (http://www.sgi.sscc.ru/mgs/programs/multalig/) has been created to search for the potential TFBS in nucleotide sequences set by the user. PMID- 11771144 TI - [Computer analysis and recognition of Drosophila melanogaster gene promoters]. AB - A new method for recognizing eukaryotic gene promoters was based on their partition and on analysis of correlations of dinucleotide frequencies for each individual fragment. The method was used to recognize the TATA-containing and TATA-less promoters of Drosophila melanogaster genes. Dinucleotide context was correlated with conformational and physicochemical DNA properties in promoter fragments. Mean values of several parameters proved to dramatically change on transition from the TATA box to its GC-rich flanks. In TATA-less promoters, specific properties were revealed in the DPE region. The method was employed in a promoter recognition program, which is available through Internet. PMID- 11771145 TI - [Analysis and recognition of promoters for erythroid-specific genes based on degenerative oligonucleotide motifs]. AB - We developed a method to search for degenerate oligonucleotide motifs specific for certain regions in eukaryotic gene promoters. A procedure of promoter recognition based on these motifs is presented. The methods are integrated within program package ARGO available for the Internet users (http://wwwmgs.bionet.nsc.ru/mgs/programs/argo). This method was applied to study erythroid-specific gene promoters. High efficiency of their recognition is demonstrated. PMID- 11771146 TI - [Algorithms for isolating regulatory signals in DNA sequences]. AB - An algorithm is proposed for extracting regulatory signals from DNA sequences. The algorithm complexity is nearly quadratic. The results of testing the algorithm on artificial and natural sequences are presented. PMID- 11771147 TI - [Sequence-determined conformational changes in the coding region of the promoter DNA on transcription complex formation]. AB - Chemical footprinting was used to study the spatial structure of bacteriophage T7 promoter D upon formation of the transcriptionally active complex with Escherichia coli RNA polymerase. Enzyme binding was shown to induce conformational changes in sites located at positions 43 and 57, several helix turns away from the transcription start. This was the first finding of a structural deformation induced by assembly of the transcription complex. The deformation was associated with specific features of the promoter nucleotide sequence, and suggested high cooperativity in the organization of the transcription complex and substantial energy perturbations caused by the enzyme. PMID- 11771148 TI - Differences in managerial behaviour between head nurses and medical directors in intensive care units in Europe. AB - We attempt to determine whether differences appear between the managerial behaviour of European intensive care head nurses on the one side and medical directors on the other. In order to come up with a managerial job and competency analysis of ICU managers, observations and interviews were performed. Additionally, focus groups consisting of ICU experts were organized. The results are discussed according to managerial behaviour taxonomies and existing competency models. There seems to be some differentiation between the two managerial positions studied. Head nurses are more involved in planning/coordinating and motivating/reinforcing activities, whereas medical directors are more involved in socializing/politicking, decision making/problem solving, interaction with others and disciplining. PMID- 11771149 TI - Effects of performance-based reimbursement on the professional autonomy and power of physicians and the quality of care. AB - The key question addressed in this study is whether performance-based reimbursement in health care affects the professional power and autonomy of physicians, and if so, whether this has any consequences for the quality of care. This cohort study examines the period 1994-98 in 11 Swedish county councils. Four hundred and eighteen physicians were studied in Stockholm County Council, which has a performance-based reimbursement system, and in ten councils without such a system. The results show that professional power and autonomy are considered to be very limited in all councils, and that they have decreased during the period studied. Professional autonomy is, however, more limited in Stockholm. The limitations in Stockholm are more related to financial considerations, whereas the limitations in the other councils are more due to guidelines and lists of recommended drugs. Professional autonomy and power were found to be important determinants for quality of care, and the physicians in Stockholm estimated the quality of care lower than their colleagues in the ten other councils. Thus, our study suggests that the performance-based reimbursement system might fail to reach the desired results due to its negative impact on professional power and autonomy. PMID- 11771150 TI - Employee experience of structural change in two Norwegian hospitals. AB - Advances in medical and technological procedures, together with changes in demography, demand structural changes in the Nordic health care systems. Few studies have focused on employee perceptions of these structural changes. This study aims to describe employee reactions following a merger between two Norwegian hospitals. A Grounded theory approach has been used in this study. The theoretical model is based on empirical data collected from employees directly affected by the structural change process. Employee resistance was found to be the core category. Three categories were found in relation to this core category; goal uncertainty, organizational culture and individual insecurity. Different perceptions and interpretations of vaguely formulated goals lead to employee resistance. The difference between the organizational cultures in the two hospitals impeded the merger according to the project plan, and very few positive results could be seen. Individual insecurity regarding the future was experienced in connection with the implementation of structural change. The authors propose a strategy to counteract resistance in similar mergers. PMID- 11771151 TI - Private medical services in acute-care hospitals in Israel. AB - The objective of this study was to assess the proposed introduction of out-of pocket funded inpatient and outpatient services (abbreviated as PMS) into government acute-care hospitals in Israel. This issue of public-private mix in not-for-profit hospitals is discussed in terms of the experience with PMS gained in selected advanced market economies. Then, the major contours of the Israeli system of health care, and the gradual evolving of patient-financed medical services within government acute-care hospitals in Israel, is described. The experience gained in the few public hospitals in Jerusalem that have been operating PMS is assessed critically. The concluding part reviews the advantages and disadvantages of these developments in public and government acute-care hospitals in Israel. It is concluded that PMS in public hospitals in Israel represents a policy aimed primarily at benefiting a select group of senior physicians in those hospitals. PMID- 11771152 TI - New funding arrangements in the Italian National Health Service. AB - In the 1990s, the Italian National Health Service (INHS) experienced a major reform introducing regionalization, quasi-markets and managerialism. The combination of quasi-markets and regionalization has produced an interesting scenario: 21 Regional Governments designing their own organizational and funding models to achieve the desired combination of equity, efficiency, freedom of choice and cost containment. This paper reports the results of a research project carried out in 1998-99 to identify such models, verify their actual states of implementation and analyse the resulting incentives for individual health-care organizations. Overall, most Regions have designed their models according to the 'LHU-centred' template, under which most public hospitals remain under Local Health Unit (LHU) control, LHUs are funded by their Regions on a capitation basis and each LHU is expected to reimburse other LHUs, Independent INHS Hospitals (IHs) and accredited private providers for services supplied to its residents. Reimbursements are activity-based according to Regional fee schedules. The major exception is Lombardy, Italy's largest and wealthiest Region, which has formally opted for the 'purchaser-provider split' template, with LHUs acting mostly as purchasers while IHs and accredited private professionals and organizations act as providers. In practice, however, many Regions still show significant features of the traditional cost-reimbursement system. PMID- 11771153 TI - 50th anniversary highlights. Epilepsy. PMID- 11771154 TI - Parkinson's disease. A half century of progress. PMID- 11771155 TI - [Chronological changes of lacunar infarctions on fluid-attenuated inversion recovery magnetic resonance images]. AB - In 26 patients with lacunar syndromes, emergence of new lacunar infarctions were identified within 13 days from onset by diffusion-weighted magnetic resonance images. The identified lacunar infarctions were repeatedly imaged using fluid attenuated inversion recovery (FLAIR) sequence up to 600 days from onset. On FLAIR images taken by 23 days from onset, lacunar infarctions showed homogeneous hyperintensity. On the later FLAIR images beyond 25 days from onset they were observed as heterogeneously hyperintense lesions in half of the patients. In the other patients, lacunar infarctions were observed as hypointense areas with a hyperintense rim beyond 41 days from onset, which indicates cystic transformation with surrounding gliosis. These FLAIR images of lacunar infarction differ from those of dilated perivascular space which is observed as an area of simple hypointensity. PMID- 11771156 TI - [Relation between autonomic dysfunction and progression of Parkinson's disease]. AB - It has been claimed that cardiovascular dysfunction in patients with Parkinson's disease is less severe than multiple system atrophy. Autonomic dysfunction, however, increases with progression of Parkinson's disease. We studied the relation between autonomic dysfunction and disease severity by cardiovascular function testing with the Valsalva maneuver. The study group comprised 20 healthy controls (age, 52.7 +/- 13.6 years) and 31 patients with Parkinson's disease (59.0 +/- 7.2 years), including 13 who were previously untreated (55.0 +/- 6.2 years) and 18 who were receiving levodopa (61.8 +/- 7.1 years). The Valsalva maneuver was done having the subject exhale into a mouthpiece with an expiratory pressure of 40 mmHg for 15 seconds. Blood pressure and RR interval were measured during the Valsalva maneuver by tonometry, using a non-invasive blood pressure monitoring system (ANS 508, Nihon Colin Co., Ltd). Baroreceptor reflex sensitivities (BRS) of the second phase (BRS II) and fourth phase (BRS IV) of the Valsalva maneuver were calculated, and blood pressure elevations during the late second phase (IIp) and fourth phase (IVp) were measured. BRS II, BRS IV, and IVp in the patients of Parkinson's disease were significantly lower than those of healthy controls. BRS II, BRS IV, and IIp, however, did not significantly differ between the previously untreated patients and healthy controls. IVp of the previously untreated patients was significant lower than that of healthy controls. BRS II and BRS IV of patients with Parkinson's disease who were receiving levodopa for less than 5 years were significantly lower than those of the healthy controls. BRS II, BRS IV, and IIp decreased as disease duration increased, while IVp was unrelated to disease duration. These results suggest that patients with early Parkinson's disease have cardiac sympathetic autonomic dysfunction with maintained baroreceptor reflex sensitivity. Reduced baroreceptor reflex sensitivity was associated with levodopa treatment in patients with Parkinson's disease. Baroreceptor reflex sensitivity decreased and vasomotor sympathetic autonomic dysfunction developed as duration of disease increased. PMID- 11771157 TI - [A patient with dermatomyositis and systemic sclerosis with preferential facioscapulohumeral muscle involvement and fatal cardiomyopathy]. AB - We report a 23-year-old man suffering from an overlap syndrome of systemic scleroderma and dermatomyositis who died from severe dilated cardiomyopathy. Because his weakness involved predominantly muscles in the facio-scapulo-humeral regions, he was initially thought to have facioscapulohumeral muscular dystrophy (FSHD) at other hospitals. However, he had also Raynaud phenomenon and low voltages on electrocardiogram. His apparent facial weakness was mainly due to atrophic skin changes. Unlike FSHD, the deltoid and levator scapulae muscles were also atrophic. Deltoid muscle biopsy performed one year earlier at another hospital showed mild myopathic changes without inflammation, but there were scattered thick-walled endomysial capillaries, suggesting inflammatory myopathy. Biceps brachii muscle biopsy in our hospital showed marked inflammation with perifascicular atrophy. In this patient, the cardiac muscle involvement progressed together with the skeletal muscle inflammation before scleroderma became apparent. PMID- 11771158 TI - [A case of Tolosa-Hunt syndrome starting from abducens nerve palsy alone]. AB - A 59-year-old man was admitted to our hospital because of right abducens nerve palsy without orbital pain. One month later right orbital pain appeared and two months later the pain changed to an aching severe pain and the right oculomotor, trochlear and trigeminal nerves were also involved. The administration of corticosteroid dramatically reduced these symptoms. The diagnosis was Tolosa-Hunt syndrome (THS) based on these findings. THS starting with abducens nerve palsy alone is rare, representing only 5.1% of 118 patients. In our patient, the newly developed dynamic MRI was able to reveal the right cavernous sinus lesion. The diagnostic usefulness of dynamic MRI for cavernous sinus lesions has been demonstrated for such cases. PMID- 11771159 TI - [A case of idiopathic brain calcification associated with dyschromatosis symmetrica hereditaria, aplasia of dental root, and aortic valve sclerosis]. AB - The patient was a 23-year-old woman. She was the product of a full-term pregnancy and normal delivery. At age 3, she was observed to have eruptions on the face and extremities. Gait disturbance and abnormal posture appeared when she was 17-year old. Mental deterioration followed several years later, and these symptoms progressed gradually. On examination at age 23, mixture of hyperpigmented and hypopigmented macules were observed on the face and the dorsal aspects of the extremities. We diagnosed her skin lesion as dyschromatosis symmetrica hereditaria (DSH) based on dermatological findings, normal minimal erythema dose and normal unscheduled DNA synthesis of her skin fibroblasts. Neurologically, she showed moderate mental deterioration, dystonic posture, dystonic and spastic gait, and generalized hyperreflexia. Laboratory examinations, including parathyroid function, were normal. Brain CT scan revealed severe symmetrical calcifications in the basal ganglia, cerebral white matter, and dentate nucleus. She also showed aplasia of dental root and aortic valve sclerosis. Her father also revealed the same clinical features including skin lesion, movement disorder, mental deterioration, and severe aortic valve calcification. So we diagnosed this patient as familial idiopathic brain calcification associated with DSH, aplasia of dental root, and aortic valve sclerosis. Constellation of these clinical features does not match any previously established type of familial idiopathic brain calcification or hereditary dystonia. However, Patrizi et al reported a patient with DSH associated with torsion dystonia who was very similar to our patient. We propose that our patient and the patient reported by Patrizi et al construct a distinct clinical entity in familial idiopathic brain calcification or hereditary dystonia. PMID- 11771160 TI - [A case of CADASIL in early stage]. AB - We report a 26-year-old woman who showed recurrent migrainous attacks and convulsions since her childhood. Neurological examination revealed no focal abnormality except mental retardation (MR). T2-and fluid-attenuated inversion recovery (FLAIR)-weighted brain MRI revealed apparent high intensities in the deep subcotical white matter. Ultrastructual studies revealed an abnormal deposition of granular osmiophilic materials (GOM) on the surface of vascular smooth muscle cells in dermis. Her mother developed recurrent strokes without risk factor since age 41. A heterozygosis Arg133Cys mutation of Notch 3 gene has already presented in patient and her mother. This case might be an early stage in CADASIL before stroke onset and suggested that systemic vasculopathy was presented in this stage. The correlation between MR and phenotype of CADASIL were unclear. PMID- 11771161 TI - [A case of myelitis caused by visceral larva migrans due to Ascaris suum presenting only with Lhermitte's sign]. AB - A 27-year-old woman was admitted because of pain radiating through her back on neck flexion that had begun a month ago. She frequently ate raw beef liver. General physical examination revealed no abnormal findings, but she showed Lhermitte's sign neurologically. Fecal examination revealed no worm eggs. Blood cell counts showed mild eosinophilia (8.2%). The IgE level was mildly increased to 397 IU/ml (normal < 250). Cerebrospinal fluid examination showed 7 cells/microliter with 50% eosinophils. A test for anti-Ascaris suum IgG antibody was strongly positive in serum as well as in cerebrospinal fluid. Cervical MRI showed high-intensity areas in the spinal cord extending from the lower medulla to the C4 spine level on the T2-weighted images, and part of the lesion at the C3 spine level was enhanced by gadolinium. Treatment with albendazole 500 mg/day for six weeks ameliorated the Lhermitte's sign and MRI lesions, and reduced the anti Ascaris suum antibody titers in the serum and cerebrospinal fluid. Larva migrans of Ascaris suum involving the central nervous system is considered to be extremely rare, but such cases showing mild neurologic impairment without systemic symptoms may have been overlooked. PMID- 11771162 TI - [A case of sarcoidosis with simultaneous involvement of the lower brainstem and the whole cervical cord and the extraocular muscles]. AB - We report a 63-year-old woman with sarcoidosis which involved the spinal cord, lower brainstem and extraocular muscules simultaneously. In this patient, uveitis developed in 1991 and the skin lesion in 1992. A biopsy of the skin lesion showed changes consistent with sarcoidosis. The ocular and dermal symptoms improved with oral corticosteroid. In October 1997, she noted the left blepharoptosis and numbness of the hands. The MRI showed diffuse swelling of the lower brainstem and the cervical and upper thoracic cord. These lesions showed high intensity signal on T2WI and low intensity signal on T1WI. T1WI with contrast enhancement revealed localized enhancement within the spinal lesion at the C4/5 level. The ocular MRI showed swelling of the left superior rectus muscle and upper levator palpebral muscle. The steroid pulse therapy and subsequent oral administration of prednisolone markedly improved the clinical symptoms. MRI after treatment showed marked improvement of both the spinal cord and ocular muscle lesions. To our knowledge, the simultaneous occurrence of myelopathy and symptomatic extraocular musculopathy in the condition has not been reported previously. PMID- 11771163 TI - [A case of Gerstmann-Straussler-Scheinker syndrome (GSS) with late onset--a haplotype analysis of Glu219Lys polymorphism in PrP gene]. AB - We report a 74-year-old man with late onset Gerstmann-Straussler-Scheinker syndrome (GSS). In this family, 3 out of 6 siblings and his father developed cerebellar ataxia and mental deterioration in their fifth decades. He complained of unsteady walking and tingling pain in the legs at the age of 70. Neurological examination revealed moderate truncal ataxia, mild limb ataxia, ataxic speech, sensory impairment, paresthesia and areflexia in the lower extremities. CSF examination showed elevated CSF and 14-3-3 proteins with a normal cell count. EEG and brain MRI demonstrated no abnormality. Somatosensory evoked potential (SEP) study showed delayed N13-N20 interpeak latencies in the upper extremities and delayed N20 at 12th thoracic spinous process, indicating dysfunction of the posterior roots or columns of the spinal cord including the dorsal horns and proximal peripheral nerve. Analysis of the prion protein gene demonstrated a Pro102Leu amino acid substitution, which is compatible with classical GSS. Haplotype analysis of the PrP gene identified a Glu219Lys polymorphism on another allele. Recently, it was confirmed that protein X, which accelerates the conversion of the normal type of PrP (PrPC) into a pathological type of PrP (PrPSc), binds to the 219th amino acid residue of PrP. Therefore, the 219Lys polymorphism theoretically inhibited formation of PrPSc and may thus have delayed the onset of the disease in this patient. PMID- 11771164 TI - [Delayed radial nerve palsy following a humeral shaft fracture]. AB - We reported a 24-year-old man with right radial nerve palsy. He had suffered from a right humeral shaft fracture approximately three years before. The fracture was treated with intramedullary nailing. Our radiograph of the right upper limb showed callus around the fracture site. A nerve conduction study revealed conduction block of the radial nerve at the lateral side of the callus. Tinel's sign was present in the median nerve at the medial side of the callus. Surgical exploration revealed that the radial nerve trunk was compressed at the callus site. The median nerve trunk was close to the callus. We decompressed radial nerve trunk, and the patient's neurological symptoms improved gradually after the operation. Delayed radial nerve palsy has been reported only rarely, whereas acute compression of the nerve sometimes occurs after humeral shaft fractures. Morever, the median nerve also was vulnerable to compression at the site of callus. These findings underscore the importance of taking into account the possibility of delayed compression neuropathy after humeral shaft fracture. PMID- 11771165 TI - [A lumbosacral cord infarction causing focally accentuated atrophy of the peroneal muscles]. AB - We report focally accentuated atrophy in a muscle due to a cryptogenic lumbosacral infarction. A 56-year-old female rapidly developed left-dominant weakness of lower thigh muscles, sensory loss of all modalities in the L5 and sacral dermatomes, and difficulty in voiding. MRI performed on day 9 showed gadolinium-enhanced lesions in the epiconus. The anterior horn lesion was most prominent in the left side of the epiconus. After one and a half months, the left lower thigh muscles became atrophic especially in the proximal part of the anterior lower thigh. After 4 months, on T2-weighted images, atrophy and high intensities were accentuated in the proximal part of the anterior lower thigh muscles where denervation potentials were abundant. A topographic relationship has been documented between the locus of a motor neuron in the anterior horn column and the position of its motor unit in the muscle. We consider that the distribution of denervation changes on muscle MRI corresponded with the anterior horn lesion on spinal MRI in our case. PMID- 11771166 TI - [Atopic myelitis and Hopkins syndrome]. PMID- 11771167 TI - [Mass screening for prostate cancer in Nagano]. AB - In three villages in Nagano, we performed mass screening for prostate cancer by digital rectal examination, transabdominal ultrasonography and serum prostate specific antigen. The cancer detection rate was 5.1% (9/178). Serum prostate specific antigen was especially useful for cancer detection. PMID- 11771168 TI - [Efficacy of a single-day administration of levofloxacin for the prevention of urinary tract infections after urogenital examinations and treatments for outpatients]. AB - The clinical efficacy of a single-day oral administration of levofloxacin (LVFX) for the prevention of urinary tract infections (UTI) after urogenital examinations and treatments for outpatients was assessed. A single-day oral administration of LVFX, 100 mg three times a day, was compared to a single dose intra-muscular injection of 100 mg netilmicin sulfate or 100 mg dibekacin sulfate. Three of 219 cases (1.4%) and 7 of 304 cases (2.3%) contracted UTI in the single-day oral administration group and the single dose intra-muscular injection group, respectively. Adverse reactions were observed in 3 of 219 cases (1.4%) and 27 of 304 cases (8.8%) in the single-day oral administration group and the single dose intra-muscular injection group, respectively. In the single dose intra-muscular injection group, UTI and adverse reactions were more severe than in the single-day oral administration group. Therefore, a single-day oral administration of LVFX was superior to a single dose intra-muscular injection of netilmicin sulfate or dibekacin sulfate in the prevention of UTI with less probability of the adverse effects. A single-day oral administration of LVFX was concluded to be sufficient for the prevention of UTI caused by examinations and treatments for outpatients. PMID- 11771169 TI - [A case of idiopathic retroperitoneal fibrosis causing acute renal failure and markedly responsive to drug therapy]. AB - We report a case of idiopathic retroperitoneal fibrosis in a 66-year-old man. He was admitted to our hospital because of acute renal failure, and emergent hemodialysis was performed. Computed tomography scanning showed a retroperitoneal mass surrounding the abdominal aorta and bilateral common iliac arteries. The mass involved bilateral ureters and acute renal failure was caused by bilateral hydronephrosis. Magnetic resonance imaging demonstrated that the mass was slightly high intensity on T2 weighted image. It was considered to be idiopathic retroperitoneal fibrosis. After inserting ureteral catheters into bilateral ureters, his renal function recovered. The layer of the fibrosis became thin by steroids and traditional Chinese medicine, and bilateral ureteral catheters could be removed two months later. At ten months after the treatment, no ureteral obstruction was observed and renal function is preserved. PMID- 11771170 TI - [Pulmonary infarction caused by the spontaneous migration of the vena caval tumor thrombus of right renal cell carcinoma: a case report]. AB - A 70-year-old male with right renal mass incidentally found by annual check-up using ultrasound, was referred to Department of Urology, Jikei University Affiliated Kashiwa Hospital. He was diagnosed as having right renal cell carcinoma with vena caval tumor thrombus extending above the diaphragm (T3c) preoperatively. The day before the scheduled day of operation, right pulmonary infarction caused by spontaneous migration of vena caval tumor thrombus of right renal cell carcinoma developed. Although arterial blood gas findings were poor, he only had low grade chest pain without shock. Therefore, we successfully performed right radical nephrectomy and thrombectomy of right pulmonary artery the next day. He was discharged 42 days postoperatively, but, he died from acute heart failure 9 months after the operation. PMID- 11771171 TI - Metastatic renal cancer arising from adenoid cystic carcinoma of the parotid gland: a case report. AB - A 40-year-old woman underwent excision of the right parotid gland tumor in 1988. The pathological examination showed adenoid cystic carcinoma. In 1993 she underwent excision of a recurrent tumor on the right face and was referred to our department because of an incidental finding of left renal tumors. She underwent nephrectomy and was diagnosed with left renal metastasis on pathological examination. In 1997 computerized tomography demonstrated multiple metastases in the right kidney, liver, lungs and brain. She died of cancer in 1998. Secondary carcinoma of the kidney is usually identified at autopsy and represents a late and poor manifestation of primary disease when diagnosed during life. The present case is unique in its primary site, pathology and clinical course. PMID- 11771172 TI - [Simultaneously detected double malignancies on a duplicated kidney associated with atrophied counterpart: a case report]. AB - A case of simultaneous double malignant tumor in the same kidney, associating renal cell carcinoma with renal pelvic transitional cell carcinoma, in a 70 year old-male was reported. On January 6, 2000 he presented with macroscopic hematuria. There were no remarkable findings on cystoscopic examination. Drip infusion pyelography and multidetector-row computed tomography demonstrated a tumor mass on the upper pole of the left kidney and atrophic right kidney. Systemic chemotherapy with CDDP, MTX and ADR was performed preoperatively. Then, hemi-left nephrectomy underwent with the diagnosis of renal pelvic tumor and renal tumor. The surgical specimen was pathologically diagnosed as transitional cell carcinoma of the renal pelvis and renal cell carcinoma of its upper pole. This is the 32nd case of simultaneous occurrence of renal cell carcinoma and transitional cell carcinoma in the same kidney in the Japanese literature. PMID- 11771173 TI - [Vesicoureteral reflux in a family]. AB - We treated 3 cases of primary familial vesicoureteral reflux (VUR). Case 1: A 6 year-old boy had a grade III VUR in the left. Case 2: A 9-year-old boy, who was the elder brother of case 1, had grade III VUR in the right and grade V VUR in the left. Case 3: An 11-year-old girl, who was the elder sister of case 1 and case 2, had bilateral grade V VUR. VUR disappeared after anti-reflux operations in all cases. PMID- 11771174 TI - [Urachal xanthogranuloma caused by a swallowed fish bone: a case report]. AB - A 30-year-old man was referred to our department with a complaint of bladder irritability and with development of high fever. Physical examination revealed a tender mass in the suprapubic area. Computed tomographic scan and magnetic resonance imaging indicated a cystic mass above the bladder dome, extending toward the umbilicus. Urachal abscess was suspected and the mass was excised en bloc with the urachus. The wall of the mass was thickened, and a linear foreign body was detected in the mass, which was considered to be a fish bone. Pathological diagnosis of the mass was xanthogranuloma. We speculated that a swallowed fish bone had penetrated the bowel and might have migrated into the urachal cyst, which induced a xanthogranulomatous change of the wall. PMID- 11771175 TI - [A prospect of molecular biology in the field of urologic oncology: mechanisms of carcinogenesis or tumor development in testicular cancer]. AB - Testicular germ cell tumor comprises about 1% of all the malignancies of males in Japan, and occurs in only one over 100,000 males annually. A susceptibility gene may be located on the short arm of the chromosome 12. Among the genes in this region, the expression of the KRAS2 mRNA was increased in testicular cancer compared to the normal testicular tissue. By DNA typing, HLA-DR4 and 0405 allele in HLA-DRB1 showed high relative risk for testicular cancer. We analyzed the expression of the WT1 gene, reported to be a growth promoter for leukemia, by quantitative reverse transcription-PCR. Relative expression of the WT1 gene was significantly increased in high-stage cases than in low-stage cases, suggesting that WT1 could be useful as a tumor marker for progression of testicular cancers. Testicular germ cell tumors are usually very sensitive to chemotherapeutic agents such as cisplatin, and p53 has been reported to play an important role in chemosensitivity. Therefore, mutations of the p53 gene or other genes downstream may be responsible for their chemoresistance. The expression of the GML (GPI- anchored molecule like protein) gene was examined in testicular cancers. Its expression was not correlated with histology or stage. However, 4 refractory cases, 2 of which were recurrent cases from stage I and the others were at high stages, showed no expression of the GML mRNA. These interesting facts suggest that the expression of GML gene could be a good marker for the prognosis of testicular germ cell tumors. PMID- 11771176 TI - [The role of MN/CA IX antigen in carcinogenesis and metastasis of renal cell carcinoma]. AB - MN/CA IX is a carbonic anhydrase (CA) isoenzyme expressed in normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in normal kidney tissues. Although the exact role of CA activity in carcinogenesis and metastasis has not been established, MN/CA9 has been suggested to be implicated in acidification of extracellular milieu surrounding the cancer cells and thus create a microenvironment conductive to tumor growth and spread. Mutations in the von Hippel-Lindau (VHL) gene cause the familial syndrome and are also found in the majority of sporadic RCC. Wild type VHL was recently described to down-regulate MN/CA9 in RCC cell lines, and the molecular mechanism of MN/CA9 and VHL in renal carcinogenesis is of interest. To investigate the mechanism of MN/CA9 activation in RCC, we examined the methylation status of this gene in RCC cell lines and human tissue samples and found that hypomethylation in the promoter region may play an important role in the expression of MN/CA9. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cells in the blood. This antigen may be a potential therapeutic target as well as diagnostic marker for RCC. Therefore, we are currently investigating whether or not MN/CA IX peptide could be an appropriate molecule for use antigen specific immunotherapy on RCC patients. PMID- 11771177 TI - [Prospects for molecular research in urological oncology: bladder cancer]. AB - This report consists of a description of our research findings relating to the mechanism of cancer metastasis and target molecules for early diagnosis or cancer therapy. First, we investigated the significance of metastasis-related genes expressed to various extents in three human bladder cancer cell lines using two in vivo models. The relationship between the gene expression pattern and the behavior of cancer cells implicated a loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer. Second, we examined the expression of human telomerase reverse transcriptase (hTERT) mRNA in voided urine samples in patients with bladder cancer. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a higher positive rate as compared with cytological examination, suggesting that the expression of hTERT in urine samples may be a useful diagnostic marker for bladder cancer. Finally, we searched for a molecule to which antisense can be applied as a treatment modality. The 150 kDa oxygen regulated protein (ORP 150), a kind of heat shock proteins, functions as a molecular chaperone in the endoplasmic reticulum. We demonstrated that the adenoviral-mediated antisense ORP150 cDNA transfer resulted in the suppression of vascular endothelial growth factor (VEGF) expression and tumor growth in vivo. In addition, the significant correlation between ORP150 and matrix metalloproteinase 2 (MMP-2) expression was observed in bladder cancer, suggesting that ORP150 functions as a molecular chaperon to MMP-2 secretion for tumor invasion. Anti sense ORP150 may therefore have a potentially stronger antitumor effect because of its multitargeting capability as a molecular chaperone. PMID- 11771178 TI - [Critical role for cell cycle regulators in androgen receptor function]. AB - Androgen plays an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute persistent activation of AR function, even during androgen ablation therapy. PMID- 11771179 TI - [The practice of the genetical diagnosis and its problems]. AB - Carcinoma is a genetic disease. The malignant phenotype is acquired only after several mutations lead to derangement in a variety of gene products. Traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. In recent years, new technology, called DNA microarray, has attracted interest. This technology promises to monitor the whole genome on a single chip so that researchers can have a better picture of the interactions among thousands of genes simultaneously. In cancers, the detection of minimal residual disease may have prognostic and therapeutic implications. Molecular tools are being used more frequently to enhance the detection of minimal residual disease in many types of cancer. Reverse-transcription polymerase chain reaction (RT-PCR) amplification of genes expressed by the tumor in a tissue-specific manner is the method with the highest diagnostic sensitivity. Quantification of tumor mRNA markers expressed by occult circulating tumor cells may be of prognostic value in a variety of neoplasms and disease stages. Medical professionals need to understand the basic concepts and principles of genetics; the role of genetics in diagnosing and managing different cancers; the ethical, legal and social issues surrounding genetic predisposition testing; and how to manage long-term care of patients at high risk for cancer. PMID- 11771180 TI - [Prospects for molecular research in urological oncology: gene therapy]. AB - The recent great advances in genetic engineering are now making possible the identification and isolation of the trigger genes of many hereditary illnesses, and the clarification of the relevant molecular mechanisms. The idea that if the genetic abnormalities responsible for illness could be established at a DNA level, treatment at the genetic level repairing damaged genes or supplying absent ones would also be possible was the incentive for the recent boom in gene therapy. Clinical research into gene therapy began in 1990 and currently over 3,000 patient cases are being studied. Some 70% of these are cancer patients. This is not simply because such patients are relatively numerous, but is also a sign of the wish, held earnestly by many researchers and clinicians as well as cancer patients and their families, to at last overcome this intractable disease. Gene therapy, so far conducted mainly in the United States, has hitherto not lived up to initial expectations in its concrete results. The reason for this results mainly in technical factors, such as the rate of success in implanting genes into target cells, the rate of successful expression of the implanted genes, and the successful achievement of specific expression at the target site. Gene therapy in the form of clinical research into renal cancer and lung cancer is now under way in Japan. It is too early at this stage to evaluate this work, but the present paper takes this opportunity to give an outline of gene therapy, and to examine its current state, future prospects and problem areas with particular reference to cancer. PMID- 11771181 TI - [Molecular epidemiology and cancer prevention]. AB - Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk. PMID- 11771182 TI - Estimation of the family cost of private nursing home care versus home care for patients with dementia in Taiwan. AB - BACKGROUND: Although overall estimates of the cost of dementia in Taiwan have been published, the relative cost of home care versus nursing home care for these patients is unclear. This study estimated the costs of home care and nursing home care for families of patients with either Alzheimer's disease or vascular dementia in Taiwan. METHODS: Data from previous reports were used to estimate costs of home care and nursing home care for families of patients with dementia, as well as the prevalence of dementia in Taiwan. RESULTS: The cost of home care per patient per month was NT$85,256 for patients with Alzheimer's disease and NT$74,152 for patients with vascular dementia. Labor was the predominant factor (96%) in home care. When the cost of labor was deducted from the calculation, the family cost per patient per month was reduced to NT$4,059 for Alzheimer's disease and NT$2,956 for vascular dementia. For patients receiving nursing home care, costs per month per patient were estimated to be NT$28,972 for patients with Alzheimer's disease and NT$31,576 for those with vascular dementia. Nursing home fees were the major component of costs incurred by families (at least 78% of total family costs). For both Alzheimer's disease and vascular dementia, payment for nursing home services amounted to approximately one-third of the labor costs of home care. CONCLUSIONS: These results indicate that nursing home placement for dementia patients provides a labor cost-savings for families in Taiwan. PMID- 11771183 TI - Possible cofactor in cervical carcinogenesis: proliferation index of the transformation zone in cervicitis. AB - BACKGROUND: Most cervical cancers arise from the transformation zone. Human papillomavirus (HPV) has been identified as playing a central role in cervical carcinogenesis. However, the lengthy period from initial HPV infection through the precancerous stage to cancer lesions implicates that the cofactors involved in the process might be random events. Our study was designed to study the relationship between the cell mitotic index and tissue inflammation of the uterine cervix. The results may help to explain the role of chronic inflammation as a possible cofactor of cervical carcinogenesis. METHODS: Using Ki-67 immunostaining, the proliferation index (PI) was determined in 30 cervices removed in hysterectomies for non-cervical diseases. The chronic cervical inflammation was graded according to quantification of inflammatory cells in adjacent stromal tissue. The relationships of these two parameters within the exocervix, the transformation zone (T-zone) and the endocervix were analyzed and their differences were compared. RESULT: A significant correlation between the microscopic inflammation scale and the PI was found in the T-zone of the cervix (p = 0.034). The PI of the T-zone, exocervix and endocervix were significantly different (p < 0.001) with scores of 66.1 (SD 26.3), 41.6 (SD 23.3) and 7.1 (SD 5.0), respectively. CONCLUSION: The results, based on modern cellular evidence, explain, at least partially the observation that cervical cancer occurs predominantly in the T-zone and suggest that implementation of antibiotic treatment in selected human papillomavirus-infected patients might decrease the development of cervical cancer. PMID- 11771184 TI - Endothelial cell loss induced by phacoemulsification occurs through apoptosis. AB - BACKGROUND: Cornea endothelial cells are nondividing cells containing pumping function which is crucial for cornea clarity and integrity. Endothelial cell loss occurs after cataract surgical procedures such as phacoemulsification. The authors hypothesize that endothelium damage occurs through apoptosis. METHODS: Ultrasound was achieved by placing a phacoemulsification probe in the anterior chamber and delivering 0% or 50% of maximum power for 2.5 min. The corneal tissue was harvested immediately, and at 1 and 7 days after the operation. Corneal tissue was stained by hemotoxylin and eosin (H&E) and evaluated by light microscopy. Endothelium apoptosis was monitored using the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay to detect DNA fragmentation. RESULTS: In corneas which underwent phacoemulsification with 0% energy, no cell loss or apoptosis was identified immediately, 1 or 7 days after the operation. Likewise, in corneas exposed to 50% energy, no cell loss or apoptosis was detected immediately after phacoemulsification. However, minimal amount of cell loss but prominent apoptosis was detected with the TUNEL assay 1 day after the operation, whereas significant cell loss but no apoptosis was detected 7 days after the operation by H&E stain. CONCLUSIONS: These results demonstrate that corneal endothelial cell loss induced by ultrasound damage occurs through apoptosis. PMID- 11771185 TI - Comparison of speech results after Furlow palatoplasty and von Langenbeck palatoplasty in incomplete cleft of the secondary palate. AB - BACKGROUND: Due to many confounding factors, it is not easy to answer which method of cleft repair is superior to others. The purpose of this study is to try to compare the treatment result of different types of palatoplasty in patients who had the same cleft type and same treatment protocol besides the method of cleft repair. We selected nonsyndromic patients with incomplete cleft of the secondary palate. The speech results after the two palatoplasties were compared. METHODS: Ninety-six children with nonsyndromic incomplete clefts of the secondary palate who received palatoplasty at the Craniofacial Center of Chang Gung Memorial Hospital from 1989 to 1997 were studied. Forty-six patients received Furlow palatoplasty and 50 patients received von Langenbeck palatoplasty. Velopharyngeal function was evaluated by speech pathologists periodically after the patient was two and half years old. Adequacy of velopharyngeal function was used as a measurement of speech outcome. RESULTS: The Furlow palatoplasty group showed excellent results with 98% (45/46) adequacy in velopharyngeal function. In the von Langenbeck palatoplasty group, only 70% (35/50) of the patients had adequate velopharyngeal function. Statistical analysis with Fisher's exact test showed a significant difference (p < 0.0001, p < 0.05). Only one patient had an oronasal fistula after Furlow palatoplasty. After von Langenbeck palatoplasty, one patient had an oronasal fistula and one had wound dehiscence. CONCLUSION: In this study, there was a better speech outcome after Furlow palatoplasty than von Langenbeck palatoplasty for repair of incomplete cleft of the secondary palate. Also, the number of complications after a Furlow palatoplasty was low. It should be a recommended treatment. PMID- 11771186 TI - Results of 12-year clinical study of giant retinal tear. AB - BACKGROUND: To evaluate the surgical results of scleral buckling alone on eyes with retinal detachment with giant retinal tears of less than 120 degrees, without inverted flap or proliferative vitreoretinopathy, and vitrectomy combined with scleral buckling with or without intraoperative usage of perfluorocarbon liquid (PFCL) in complicated cases. METHODS: Retrospectively, we reviewed giant retinal tear cases treated at Chang Gung Memorial Hospital, Kaohsiung, Taiwan between January 1, 1989 and August 31,2000. The surgical techniques consisted of standard three-port pars plana vitrectomy combined with scleral buckling in complicated cases, PFCL used intraoperatively in later cases, and scleral buckling alone in minor cases. RESULTS: A total of 47 consecutive eyes with giant retinal tears with retinal detachment in 45 patients with no previous history of ocular penetrating injury or vitreoretinal operations were enrolled in this study. The follow-up period was at least three months for all patients. Thirty four eyes (72.3%) had giant retinal tears of less than 180 degrees, 12 eyes (25.5%) had tears between 180 degrees and 270 degrees, and one eye had two giant retinal tears. Scleral buckling combined with vitrectomy was performed in 36 complicated eyes (76.6%), PFCL was used intraoperatively later in 24 eyes, and scleral buckling was used alone in 11 minor cases (23.4%). Thirty eyes (63.8%) gained reattachment after the first surgery. Altogether, the retinas of 38 of 47 eyes (80.9%) remained attached at the last follow-up examination. CONCLUSION: In minor cases of giant retinal tear, scleral buckling alone without vitrectomy may be considered the primary surgical procedure. In complicated cases, using PFCL intraoperatively not only affords many advantages during surgery, but also raises the retinal reattachment rate. PMID- 11771187 TI - Extreme insulin resistance syndrome. AB - Congenital extreme insulin resistance syndrome has rarely been reported in Taiwan. In 1982, a girl of a consanguineous marriage was noted to have increased body hair, an enlarged clitoris, and acanthosis nigricans at birth. Two months later, she received an operation for bilateral polycystic evaries. She was found to have diabetes at 8 years old and was treated with insulin. In March 1999, she was referred to our clinic with growth retardation and poor glycemic control. She had a characteristic face with a saddle nose, broad mouth, large low-set ears, absence of subcutaneous fat, and deformed nails. Although a very high dose of insulin (> 10 IU/kg/day) was used, her glycemic control was very poor (HbA1c 13.8%). Pediatricians should remain alert for the manifestations of extreme insulin resistance. PMID- 11771188 TI - Selective termination of aneuploidy utilizing rapid fluorescence in situ hybridization detection techniques. AB - Twin pregnancy following assisted reproductive technology with a euploid fetus and a coexisting aneuploid co-twin constitutes a conflicting situation; therefore, it is important for the genetic constitution of each co-twin to be diagnosed accurately and promptly for parental genetic counseling and subsequent aggressive management. A 35-year-old woman, gravida 1, with a 2-year history of infertility, presented bilateral fallopian tubal obstruction at her infertility workups, for which she received in vitro fertilization; subsequently she conceived a twin pregnancy. She underwent genetic amniocentesis at 16 weeks' gestation, as indicated by an advanced maternal age. Presented with the diagnosis of twin pregnancy with discordancy for trisomy 21, a rapid fluorescence in situ hybridization (FISH) technique for aneuploidy mapping was applied for subsequent abdominal selective fetal reduction. The FISH technique facilitates the rapid analysis of uncultured amniocytes. Normal (disomic) and trisomic samples can be distinguished clearly and rapidly for subsequent selective fetocide. The FISH technique is an important tool in prenatal diagnosis and clinical applications. PMID- 11771189 TI - Reversible infra-Hisian atrioventricular block in acute myocarditis. AB - Symptomatic second- or third-degree atrioventricular (AV) block at any anatomical level is a class I indication for permanent pacemaker implantation. We describe a 44-year-old male with acute viral myocarditis who suffered from syncope followed by a seizure attack associated with AV conduction disturbance. His initial electrocardiogram in our emergency room revealed sinus tachycardia with 2:1 AV conduction and a right bundle branch block QRS morphology with a ventricular rate of 60 beats/min. Because of episodic slowing of the heart rate below 40 beats/min, he received 1 mg atropine intravenously which increased the atrial rate but further worsened the AV conduction, resulting in ventricular asystole for more than 30 seconds associated with loss of consciousness and seizure-like activity. He was immediately paced transcutaneously and transferred to the catheterization laboratory to receive temporary transvenous cardiac pacing. The cardiac catheterization study showed a normal coronary angiogram and very mild diffuse hypokinesis. Electrophysiological studies revealed advanced infra-Hisian AV block. The infra-Hisian AV block, however, resolved rapidly in 2 days. The patient did not receive a permanent pacemaker and remained asymptomatic with normal electrocardiogram over 1 year of follow-up. We suggest that symptomatic infra-Hisian AV block due to viral myocarditis can be reversible, and implantation of a permanent pacemaker may not be necessary. PMID- 11771190 TI - Hepatic focal nodular hyperplasia in children: report of three cases. AB - Hepatic focal nodular hyperplasia is very rare in children. We present 3 cases aged from 8 to 17 years. All of them are girls, none of whom used oral contraceptives. Case 1 was a hepatitis B carrier and was incidentally found to have focal nodular hyperplasia (FNH). The other 2 cases presented with abdominal pain. Abdominal computed tomography revealed a solitary liver tumor in cases 2 and 3, but no abnormalities in case 1. A 7-cm tumor was located in the left lobe of the liver with compression of the stomach in the 2nd case. Abdominal magnetic resonance imaging (MRI) showed a mass with isointense density to liver parenchyma on T1WI and hyperdensity on T2WI in the 1st and the 3rd cases. The inferior vena cava was compressed and displaced anteriorly in the 1st case. Because of differences in the clinical presentation and imaging studies, the 1st and 2nd cases received resection while the 3rd case was treated conservatively. Pathologic findings confirmed the diagnosis of focal nodular hyperplasia in all 3 cases. We emphasize the importance of an MRI scan in the diagnosis of hepatic focal nodular hyperplasia, and different clinical manifestations and imaging studies may lead to different management. PMID- 11771191 TI - Bridging bronchus in an infant demonstrated by direct coronal computed tomography and three-dimensional rendering display. AB - Bridging bronchus is a rare anomaly in which the right lower lobe bronchus arises from the left main bronchus and bridges the lower mediastinum. The first reported case was diagnosed at autopsy in 1976. The second reported case was diagnosed by bronchography confirmed at autopsy in 1980. We describe a 9-month-old infant with such an anomaly. Our patient presented with cough, shortness of breath, and rhinorrhea with no fever or sputum production. The physical examination revealed only coarse breath sound and chest retraction with no other abnormalities. Chest radiography showed decreased lung volume and shifting of the mediastinum to the left. Diagnosis of this anomaly was not possible with computed tomography (CT) axial imaging. Direct coronal CT and 3D rendering with the surface-shaded display technique showed a small right upper lobe bronchus and proximal stenotic left main bronchus, with the intermediate bronchus originating from the left main bronchus and crossing the midline to enter the contralateral lung. PMID- 11771192 TI - [Anniversary Symposium with a look into the future]. PMID- 11771193 TI - [Learning to die/practice means learning about life with an awareness of death]. AB - Living with the understanding that one must take leave of life means being able to restore the past. Living with the understanding that one must take leave of life means new insight into the present. Living with the understanding that one must take leave of life means creating an inspiring future. These three theorems are discussed in detail based on conversations with elderly persons. PMID- 11771194 TI - [Old European "ars moriendi" (the art of dying) as a challenge for our approach to death and dying]. AB - In Europe, there was once a time when death and dying were approached differently than they are today. Ars moriendi was cultivated as a means of consciously preparing for death. In modern times, constant thoughts of death are no longer considered as necessary for leading a responsible life. PMID- 11771195 TI - [Themes of dying and death in the music of Johann Sebastian Bach]. AB - Johann Sebastian Bach's music evokes feelings and provokes thoughts about the meaning of human existence, but also thoughts and feelings with regard to death and dying. By virtue of their earthliness and chimerical divinity, musical compositions by Bach are all-embracing, transporting the listener into a third dimension that reveals the unexplored depths of time and eternity. PMID- 11771196 TI - ["Enmeshed in stories". The story concept as experiential practice of arms moriendi]. AB - The way we deal with death and dying in the world of high-tech medicine has shifted from interpretation to action. One's own dying has become professionalized and delegated to doctors. Against this backdrop, what does the "story concept" proposed by D. Ritschl provide us in terms of rehabilitating the art of dying or "Ars Moriendi"? Can it be considered a category for reflection about death and dying? PMID- 11771197 TI - [Who is interested in quick and intentional death--reflections of a public health economist]. AB - Healthcare economics deals with the concepts of direct, indirect and intangible costs and the interrelated timeframes. Using two concrete examples, the author will examine the utilization patterns of direct and indirect costs and take a look at the participants who might be interested in a quick and intentional death. PMID- 11771198 TI - [Increasing life expectancy: adding quality of life to those years]. AB - Demographic changes are a challenge for the health care system. Based on three case reports, the potential for improving preventive, rehabilitative, and palliative care in older persons is presented. The article discusses the method of multidimensional geriatric assessment. PMID- 11771199 TI - [Autonomy and human dignity--fiction and reality]. AB - Definition and lived-in reality of "autonomy" an "human-dignity" may differ as can be shown by means of a patient's situation: it varies whether patient, relatives, general practitioner or hospital doctor are involved. It is most important to assure these terms not only to be fiction but to become a lived reality. PMID- 11771200 TI - [Practice guidelines for antibiotic therapy of respiratory tract infections in routine practice]. PMID- 11771201 TI - [Corticosteroid-sensitive aseptic abscess associated with inflammatory bowel disease. An emerging syndrome]. PMID- 11771202 TI - [Epidemiology and management of suspected pneumonia in nursing home residents]. AB - OBJECTIVE: We conducted a descriptive epidemiology study to examine the conditions of management of infectious lung disease in institutionalized elderly populations (population profile, diagnostic and therapeutic modalities) and to analyze the general and mental consequences in terms of independence (impact of the infectious event on the subject's life style). PATIENTS AND METHODS: A pragmatic survey was conducted by a multicentric observatory composed of 573 general practitioners, practicing in nursing homes. The series included 1790 patients aged over 70 years and residing in nursing homes who developed infectious lung disease over a 10-month period. The MMSE score was used to assess mental status and the Barthel index to assess functional handicap. Each patient was evaluated at the time of the final diagnosis (prescription of an antibiotic or decision for hospitalization) and at most 3 days after the end of this treatment or at discharge from hospital. RESULTS: The elderly population (84 +/- 7 years) was predominantly composed of women. The patients were treated for an acute respiratory infection considered in 30% of the cases to be acute lobar pneumonia. Subgroups of patients were identified for analysis: death (3.7%), x ray confirmation of the diagnosis (11.5%), hospitalized patients (10.2%). In addition to major deterioration of the general health status, a consequence of the infection more than of the severity of the respiratory symptoms, the development of an acute episode coincided with reduced intellectual functions and onset of a state of confusion. In 70% of the cases, this resulted in a loss of independence of variable importance--simple difficulty for moving around to major functional handicap. The infectious episode was cured or improved (persistence of minor signs not requiring specific treatment) in 94.3% of the cases with appropriate antibiotics: single-drug regimen in 93.7% give per os (75%) or intravenously (25%) using aminopenicillin (with or without a beta lactamase inhibitor) in 80% of the cases. Antibiotic treatment was associated with physical therapy in more than half the cases, and with general conticosteroids in 40%. The treatment scheme was modified in 9.4% of the cases (change of antibiotic in 6%). CONCLUSION: This survey confirms the high risk related to general conditions in elderly institutionalized patients who develop respiratory infection. More than the infection itself, the rapid degradation of the general health status, or decompensation of comorbid states can create life-threatening situations or favor the development of irreversible handicaps. PMID- 11771203 TI - [Septic shock with liver abscess in an immunocompetence patient. Presentation of an unusual Fusobacterium nucleatum infection]. AB - BACKGROUND: Fusobacterium septicemia with septic metastasis is a very rare and potentially serous condition when complicated by septic shock. Most cases have been described in patients with humoral immunity disorders and/or severe underlying chronic disease. CASE REPORT: A 24-year-old immunocompetent woman with a tonsil infection developed F. nucleatum septic shock with liver abscess formation. Outcome was rapidly favorable with antibiotic treatment and adapted intensive care, probably favored by the absence of an associated immune deficit. DISCUSSION: Despite its low incidence, F. nucleatum should be entertained as a possible cause of septicemia originating from a pelviperitoneal, pulmonary with abscess formation, or upper airway infection. Proper diagnosis is essential due to the risk of poor prognosis. Fusobacterium nucleatum is a commensal strictly anaerobic bacteria of the buccal cavity. It can cause dental and upper airway infections. Septicemia with secondary localization of F. nucleatum is very rare and the severity depends on the presence of associate septic shock. The immunopathological implications of these infections remain to be elucidated. PMID- 11771204 TI - [General antibiotic therapy in routine practice. Exacerbations of chronic bronchitis, acute sinusitis in adults, lower respiratory tract infections in children, acute sinusitis in children, acute otitis media]. PMID- 11771205 TI - [The relationship between Chlamydia pneumoniae and atherosclerosis]. AB - BACKGROUND: Risk factors for arthrosclerosis have been well identified. More than ten years ago, an infectious process was incriminated, particularly the pathogenic effect of Chlamydia pneumoniae in the development of atheromatous lesions responsible for ischemic cardiovascular diseases. DATA BASES: Several approaches have been used to assess the presence of a relationship between C. pneumoniae and the development of cardiovascular disease. Serological, histopathological (study of the atheromatous plaque), pathophysiological, and finally animal studies using models reproducing the human disease have generally favored an association. Therapeutic trials, especially those testing roxithromycin or azithromycin have demonstrated the action of secondary prevention of ischemic heart disease (unstable angina, myocardial infarction). CONCLUSION: The notion of an association between these two factors is biologically plausible. Several points remain to be clarified, particularly the need to develop a reliable diagnostic method for C. pneumoniae infections. It would also be useful to prove the viability of the pathogen within atheromatous plaques and finally to design studies of immune response to C. pneumoniae infections. Prospective therapeutic trials for primary prevention of cardiovascular disease would be most informative but would be most difficult to conduct. PMID- 11771206 TI - Prophylactic urgent carotid endarterectomy in symptomatic patients--is it worthwhile? PMID- 11771207 TI - Prophylactic urgent revascularization of the internal carotid artery in the symptomatic patient. AB - BACKGROUND: The symptomatic patient showing a string sign or ulcerative stenosis of the internal carotid artery (ICA) is subject to a high risk of arterial thrombosis or persisting intracranial embolization during the waiting period before operative revascularization. PATIENTS AND METHODS: During one year 186 operative revascularization procedures of the ICA were performed on the symptomatic patient. 26 of them fulfilled the prophylactic urgency criteria: symptoms of the cerebrovascular insufficiency and a string sign or ulcerative stenosis of the ICA with ulceration greater than 2 mm in depth. These results were compared to the control group of the 157 procedures under elective circumstances. RESULTS: Mean clamping time of the urgency and the elective patients were 23.8 min vs. 24.5 min and operation time 50.1 min vs. 54.3 min. None of our urgency patients presented new neurological defects in the postoperative phase, while this occurred in 3.8% in the elective group. Mortality rate in the elective group was 2.7% and 0% in the urgency group. Furthermore, there were fewer local complications in the urgency group. CONCLUSION: The urgent indication for the desobliteration of the ICA showing a symptomatic string sign or ulcerative stenosis can be recommended. Early thrombosis or neurological defects during the waiting period may be prevented without increasing complication rates. PMID- 11771208 TI - Complete compression ultrasound for the diagnosis of proximal and distal deep venous thrombosis--a retrospective outcome study. AB - BACKGROUND: Compression ultrasound is considered the preferred test for the diagnosis of deep vein thrombosis of the leg (DVT). Since sensitivity for distal thrombosis is low-additional tests are required. We developed a protocol of complete compression ultrasound of all venous segments of the leg (CCUS). A retrospective outcome study was performed to get an estimate of the rate of indeterminate results necessitating repeated testing as well as for the clinical safety of CCUS in a cohort of consecutive, unselected patients. PATIENTS AND METHODS: Case records of all patients referred for clinical suspicion of deep vein thrombosis within a three months period were reviewed. Patients with negative CCUS were followed directly or via the general practitioner in order to know whether an episode of venous thromboembolism had been documented since the initial CCUS. RESULTS: 132 inpatients and 154 outpatients were identified. Clinical probability was high in 50 patients, medium in 142, and low in 94. The first CCUS was negative in 209 cases. Five patients (1.8%) had repeated CCUS within the next 7 days because of incomplete visualisation of the distal veins and turned out to be negative as well. Of all 214 patients with negative CCUS a clinical follow-up information was obtained after 168 +/- 25 days. Five patients had died, none due to pulmonary embolism. In two patients deep vein thrombosis had been documented (0.9% [95% CI: 0.1-3.3%]) 148 and 172 days after CCUS, respectively. CONCLUSION: CCUS for diagnosis of DVT needs to be repeated in very few cases only. Clinical safety seems to fall into the same range as with combined algorithms and should be tested in a prospective design. Patients with medium and high probability showed a very low incidence of DVT within three months following CCUS; therefore, they may be included in a prospective outcome study. PMID- 11771209 TI - Incidence of deep venous thrombosis after thoracotomy. AB - BACKGROUND: Incidence of deep venous thrombosis (DVT) after thoracotomy has not been widely studied. DVT is a frequent complication in major surgery involving abdominal and pelvic areas and lower extremities. The aim of the present study was to evaluate the rate of postoperative DVTs after surgery of the lung. METHODS: In this prospective study with 25 patients undergoing thoracotomy both legs were studied with venous duplex imaging (VDI) preoperatively and on the second postoperative day. Clinically manifest thromboembolic events during one month postoperative period were reviewed from the patients' records. DVT prophylaxis included compression stockings and early mobilization without low molecular weight heparin. RESULTS: Frequency of postoperative DVTs was 4%. There were no clinically manifest thromboembolic events during one-month postoperative period. In 8% of the patients an old DVT was found preoperatively. CONCLUSIONS: Based on this material, incidence of DVT is low after thoracotomy. Early mobilization and the use of compression stockings may be a sufficient form of prophylaxis in these patients. The relatively small sample size and the use of ultrasound as a screening method should be noted in judging the results. PMID- 11771210 TI - Cost-effectiveness of screening for familial abdominal aortic aneurysms. AB - BACKGROUND: Screening for familial abdominal aortic aneurysms (AAA) is widely recommended. To analyze cost-effectiveness of screening for familial AAAs incremental cost-effectiveness (C/E) analysis based on an ultrasound screening among relatives and a decision model of screening program was compared to a baseline situation without systematic screening. PATIENTS AND METHODS: 74% (238/322) of first-degree relatives of 150 consecutive AAA patients were screened at HUCH (Helsinki University Central Hospital). Effectiveness and costs of treatment were assessed using the Finnish Hospital Discharge Register and from survival analysis of 1130 AAA patients who underwent elective or emergency surgery in HUCH. To form incremental C/E-ratios the existing clinical practice was compared to a screening program for male siblings. Hypothetical screened and control cohorts of 1000 male relatives were used to create the decision model. Parameters in C/E-analyses were derived from our own data except for growth and rupture rates. A sensitivity analysis was carried out. RESULTS: The incremental effectiveness in life-years gained by the screening of male siblings was 92 years with incremental C/E-ratio of FIM 33,000 ($6200). According to sensitivity analysis the C/E-ratios were robust for all variables tested. CONCLUSIONS: Screening of male siblings of AAA patients produces incremental life-years at low cost thus screening of male siblings is highly recommended. PMID- 11771211 TI - Spiral-CT angiography to assess feasibility of endovascular aneurysm repair in patients with ruptured aortoiliac aneurysm. AB - BACKGROUND: To evaluate spiral computed tomography (SCT) angiography for assessment of feasibility of endovascular aneurysm repair (EVAR) in patients with ruptured aortoiliac aneurysm (AAA). PATIENTS AND METHODS: 24 patients (mean age 74 years; range, 69 to 82 years) with suspicion of ruptured AAA and stable hemodynamics were preoperatively examined by using a SCT scanner in the emergency room. SCT angiography was performed from the suprarenal aorta to the femoral bifurcation after a fixed injection delay time of 30 seconds. After that a venous phase SCT scan, beginning at the last image position and ending at the upper thoracic aperture, was performed. RESULTS: The mean acquisition time of the SCT scan was 80 seconds (range 70 to 100 seconds), the mean overall procedure time, including image reconstruction, 5 minutes (range, 4 to 6 minutes). 2D images were directly evaluated during CT data acquisition, and 3D image reconstructions within 10 minutes (range, 8 to 11 minutes) after the SCT scan. AAA rupture was assessed in 14/24 patients (58%): in 10/14 patients (71%) rupture was contained to the retroperitoneum, and in 4/14 patients (29%) intraperitoneal rupture was observed. Successful EVAR was performed in 6/14 patients (43%) with ruptured AAA, and in 8/10 patients (80%) without ruptured AAA. Open surgery was exclusively performed in 6/24 patients (25%) with inappropriate anatomy for EVAR and in 4/24 patients (17%) with intraperitoneal rupture. CONCLUSIONS: Spiral computed tomography angiography is a reliable technique to assess feasibility of endovascular aneurysm repair in patients with ruptured aortic aneurysm. However, it can only be recommended for patients with stable hemodynamics, despite of the short acquisition time. PMID- 11771212 TI - Impaired venous hemodynamics in a minority of patients with chronic leg ulcers due to sickle cell anemia. AB - BACKGROUND: Chronic or recurrent leg ulceration occurs in 25% of sickle cell anemia patients, but not in the remaining 75%. Doppler studies of venous function were normal in 16 sickle cell anemia patients with leg ulcers. PATIENTS AND METHODS: Venous Duplex Ultrasound was used to study 33 sickle cell anemia patients with chronic leg ulcers. RESULTS: Six of the 33 patients had venous reflux in at least one leg. CONCLUSIONS: Venous insufficiency may contribute to the development of leg ulcers in a minority of sickle cell anemia patients. A minority of sickle cell anemia patients with chronic leg ulcers can be shown to have leg venous reflux by duplex ultrasound imaging. PMID- 11771213 TI - Low level laser treatment of primary and secondary Raynaud's phenomenon. AB - BACKGROUND: Patients who had been treated with low level laser (LLL) for their digital ulcers reported an impressive improvement of their symptoms of episodic digital ischaemia. Therefore this pilot study was performed to evaluate the efficacy of LLL as a new non-drug non-invasive treatment for patients with primary and secondary Raynaud's phenomenon (RP). PATIENTS AND METHODS: Forty patients (29 female, 11 male, mean age 51 years) with active primary (28%) and secondary (72%) Raynaud's phenomenon received 10 sessions of LLL distant irradiation during winter months. Assessment of subjective and objective parameters was performed at baseline, one week after the last session and three months later. Variations of subjective parameters as number of daily acute episodes and severity of discomfort were assessed by a coloured visual analogue scale. A standardised cold challenge test using computed thermography of continuous temperature recordings by means of infrared telethermography was used to assess the digital blood flow. RESULTS: A significant improvement was noticed clinically and thermographically after 6 weeks and 3 months, respectively (p < 0.0001). CONCLUSIONS: These data suggest that LLL treatment has a good short and medium term effectiveness in patients with Raynaud's phenomenon. PMID- 11771214 TI - Acute adrenocortical insufficiency due to heparin-induced thrombocytopenia with subsequent bilateral haemorrhagic infarction of the adrenal glands. AB - A 56 year old male developed bilateral massive adrenal haemorrhage (BMAH) resulting in chronic adrenal insufficiency in the course of heparin-induced thrombocytopenia (HIT)-syndrome. Thrombosis of the central adrenal vein (CAV) with subsequent adrenal haemorrhagic infarction is the most probable cause of the rare association of HIT and BMAH. The exorbitantly high catecholamine plasma levels within the CAV in addition to immunogenic platelet activation are discussed as possible underlying pathophysiological mechanisms. PMID- 11771215 TI - [Initial manifestation of thromboangiitis obliterans as necrotizing colitis]. AB - Necrotizing colitis as primary manifestation of Buerger's disease. We report the disease process of a 41 year old woman, who was referred to our clinic with intermittent claudication of the leg. She has been an excessive smoker since early youth. Three years ago a hemicolectomy was carried out because of a necrotizing colitis. The clinical, angiographic and histologic findings are presented. Finally the frequency of intestinal Buerger's disease and the types of clinical course are discussed. PMID- 11771216 TI - [Single intervention for treatment of Salmonella typhimurium-induced symptomatic abdominal aortic aneurysm with spondylitis]. AB - Simultaneous treatment of Salmonella typhimurium-induced symptomatic abdominal aortic aneurysm with associated spondylitis. Bacterially infected aneurysms associated with local spondylitis, while representing a potentially fatal clinical picture, are an operative challenge for vascular surgeons and orthopaedic surgeons alike. In this context, the concurrent occurrence of an infection with Salmonella typhimurium as a causative agent is a rare observation. The case report gives an outline of the simultaneous vascular and orthopaedic surgical procedure. The subrenal mycotic aneurysm was removed in a first step. The continuity of the aorta was restored centrally through an autogenic aortic graft with caudal anastomosis to a dacron vascular prosthetic tube. Initially, the latter was chosen of excessive length so as to facilitate the orthopaedic surgeon's approach. Upon completion of stabilising surgery of the vertebral column, the dacron tube was reduced in length as necessary and the surgical area was enclosed with an omentum majus plastic mesh. No complications were noted during the 18-month follow-up period. PMID- 11771217 TI - [Mondor phlebitis associated with hepatitis C]. AB - Mondor's disease in association with hepatitis C. We report a case of a 40 years old patient suffering from Mondor's disease. Neither a malignancy nor a disturbance of the clotting system was found. This case is remarkable for the association with hepatitis C. PMID- 11771218 TI - Angiography, CT and MR imaging of a high vena cava inferior interruption in a patient with Hirschsprung disease. AB - We report on a high vena cava inferior interruption immediately at the insertion to the right atrium in a patient with Hirschsprung disease assessed by angiography, CT, and MRI. Hirschsprung disease is frequently associated with Down, Undine, Waardenburg, Bardet-Biedl, Smith-Lemli-Opitz and Goldberg Sphrintzen syndromes. We suggest that the association of these two malformations are most likely interrelated and should be considered as a new syndrome. PMID- 11771219 TI - Thrombosis extension varies with different tumours. PMID- 11771220 TI - The painful shoulder. PMID- 11771221 TI - Disease-modifying drugs in rheumatoid arthritis. PMID- 11771223 TI - A strategy for exam success. PMID- 11771222 TI - Diagnosing fibromyalgia. PMID- 11771225 TI - The value of exercise. PMID- 11771226 TI - A delayed mitral valve operation. PMID- 11771227 TI - Key developments in rheumatology. PMID- 11771228 TI - Having trouble with the use of mobile phones within the perioperative environment. PMID- 11771229 TI - The role of the professional officer. PMID- 11771230 TI - The World Health Organisation. PMID- 11771231 TI - Caring carers. PMID- 11771232 TI - Developments in the care of patients who require surgery for an abscess. AB - This is the first of a series of three articles which won the Alison Bell Writer's Award this year. Jill Biggins won first prize for this article which looks at a way of improving the patient's experience of day surgery. The Writer's Award is sponsored by NATN and Regent Medical. PMID- 11771233 TI - Clean/dirty scrub technique. Is it worth the effort? AB - An intraoperative critical incident occurred which questioned the validity of the practice of clean and dirty technique in bowel surgery and its role in the prevention of postoperative wound infections. Following the incident, a literature review and a clinical audit were conducted to determine the recommended use of this technique, and to explore its application in clinical practice. The results of the review and the audit are presented and a list of recommendations for practice is made. PMID- 11771234 TI - Doing deals. AB - In the previous two articles in this series, Fiona Westwood looked at the importance of managing conflict positively and influencing people without the use of direct authority. We now move on to the next management tool--the ability to 'do deals' with people. PMID- 11771235 TI - Contamination of the surgical field. AB - Is there sufficient evidence to suggest that the wearing of face masks is imperative during surgical procedures for maximum patient protection? Or is it just another ritual that needs to be re-examined in the light of today's emphasis on evidence-based medicine. Should we be re-educating theatre staff that the wearing face masks is more for their own protection than for that of the patient? To help us towards some conclusions, Peggy Edwards presents the results of her review of the literature on the face mask debate. PMID- 11771236 TI - [Gap junctions: structute, functions, and regulation]. PMID- 11771237 TI - ["Substrate inhibition"--one of the aspects of substrate specificity of cholinesterases in vertebrates and invertebrates]. PMID- 11771238 TI - [Current views on the physiology of cerebral circulation: comparative analysis]. PMID- 11771239 TI - [Chemical structure and photochemical activity of the abiogenic flavin substrate]. PMID- 11771240 TI - [Effect of the vacuum ultraviolet radiation on the abiogenic synthesis of adenine nucleotides in the presence of lunar soil]. PMID- 11771241 TI - [The effect of biogenic amines and polypeptide hormones on the activity of protein kinase and adenylate cyclase from muscles of the mollusk Anodonta cygnea]. PMID- 11771242 TI - [Substrate inhibition of cholinesterase from the hemolymph of the Pacific gastropod Neptunea eulimata]. PMID- 11771243 TI - [Activation of Na+/H+-exchange in erythrocytes of the river lampreys Lampetra fluviatilis]. PMID- 11771244 TI - [Ultraviolet absorption spectra of lipid extracts of the lampreys and rat brain and their relationship with fatty acid composition]. PMID- 11771245 TI - [Thermoresistance of erythrocytes and hemoglobin during acclimation of the rainbow trout Salmo irideus]. PMID- 11771246 TI - [Analysis of Na+ and water transport in the pigeon and chicken kidney using lithium clearance during water and salt load: renal netto-reabsorption and netto secretion of Li+ ]. PMID- 11771247 TI - [Effect of serotonin on the development of luteinizing hormone-releasing hormone system in Wistar rat embryos]. PMID- 11771248 TI - [Adaptation of the mouse auditory system to perception of ultrasonic communication signals]. PMID- 11771249 TI - [Argyrophilic and nitroxydergic bipolar neurons (Lugaro cells) in the cerebellum of Pholidapus dybowskii]. PMID- 11771250 TI - [Life is existence, interaction (functioning) and reproduction of unique highly organized nucleotide and amino acid sequences]. PMID- 11771251 TI - [Evolutionary oncoendocrinology]. PMID- 11771252 TI - [Calcium and magnesium metabolism in Chironomus (Di[tera, Chironomidae) larva]. PMID- 11771253 TI - [An apparatus for the controlled artificial pulmonary ventilation]. PMID- 11771254 TI - [Chemiluminescent method for health status evaluation in children]. PMID- 11771255 TI - [Lipid peroxidation in plasma and erythrocyte membranes in basketball players]. PMID- 11771256 TI - [Seasonal variations in parameters of health and stress response in adolescents]. PMID- 11771257 TI - [Determination of predicted normal resting frequency of cardiac contractions in humans]. PMID- 11771258 TI - [Development of reserve capacities of the pulmonary respiratory function in schoolchildren]. PMID- 11771259 TI - [Age-specific characteristics of physiological responses of five- to seven-year old children to working with personal computers]. PMID- 11771260 TI - [The constitutional factor of a child growth and maturation]. PMID- 11771261 TI - [Transport and consumption of oxygen by children from the Far North]. PMID- 11771262 TI - [Neurophysiological study of hemispheric organization of the EEG spectrum in mental infantilism in adolescents]. PMID- 11771263 TI - [The role of hemispheric functional specialization in the analysis of the relationship between signal and nonsignal information during image shape classification]. PMID- 11771264 TI - [Sensorimotor functions in human ontogenesis and their correlation with the nervous system properties]. PMID- 11771265 TI - [Effect of hypoxic hypoxia on spontaneous electric activity of the human brain]. PMID- 11771266 TI - [Cutaneous afferent signal as a modulator of the heteronymous effect of primary muscle afferents]. PMID- 11771267 TI - [Types of systemic responses of human hemodynamics and hemostasis to multiple occupational migrations to Polar Circle regions]. PMID- 11771268 TI - [Hemorheological methods in diagnosis of venous circulation]. PMID- 11771269 TI - [Early diagnosis of long-term lead neurotoxic effects based on the heart rhythm analysis]. PMID- 11771271 TI - [Current methods of evaluation of functional status of the autonomic nervous system]. PMID- 11771270 TI - [Diagnosis of aging. Part I. Reliability of linear regression models of biological age]. PMID- 11771272 TI - [A novel method of analysis of ligand-polynucleotide adsorption isotherms]. AB - The adsorption of ethidium bromide on the synthetic double-stranded polyribonucleotide poly(G)poly(C) was investigated by adsorption spectroscopy. The adsorption isotherms were analyzed in the framework of the Crothers-Gursky model. It was shown that adsorption parameters (e.g., binding constant) may also be determined from the analysis of dispersion of some bound molecules. In some cases this method may be more convenient. PMID- 11771273 TI - [Constants of binding of Pb(II) ions with DNA at various ionic strength]. AB - The energetics of Pb(II) ion binding to DNA was determined from their binding isotherms by equilibrium dialysis and atomic absorption spectroscopy at different ionic strengths. Two types of binding of Pb(II) ions to DNA at different NaCl concentrations were observed. PMID- 11771274 TI - [Theoretical approaches for evaluation of DNA-protein interactions]. AB - The notion of the DNA-recognizing segment of a protein for three-dimensional structures of DNA-protein complexes was formalized. Algorithms for calculating two parameters, hydrogen bonds and hydrophobic contacts, that characterize the interaction of the DNA-recognizing segment of the protein with the groove DNA major were proposed. DNA-recognizing protein segments in three-dimensional structures (of complexes) were classified according to these two parameters. These data were compared with the classification of the corresponding DNA recognizing domains according to structure. The contribution of each pair amino acid residue-base to the interaction of protein with the DNA major groove was calculated. PMID- 11771275 TI - [Characteristics of electrostatic interaction of Escherichia coli RNA polymerase with promoters of T4 phage DNA]. AB - A comparative analysis of electrostatic potential distribution for "early" T4 phage promoters was undertaken. The data obtained indicate that there are some particular elements in the patterns of electrostatic potential distribution of promoter DNA specific for promoter groups differing by their functional response to ADP-ribosylation of the alpha-subunit as well as to rpoB403- or rpoB409 mutationals of the beta-subunit of RNA-polymerase. PMID- 11771276 TI - [Functionally important sites in the elongation factor EF-Tu from Thermus aquaticus: analysis of fine structural changes upon binding of guanosine-3' triphosphate and guanosine-3'-diphosphate]. AB - High-resolution data were used to analyze conformational changes of the main chain in two functional states of the ribosome elongation factor EF-Tu from Thermus aquaticus: the inactive state with guanosine-3'-diphosphate and the active state with guanosine-3'-triphosphate. Earlier only major changes in the effector loop of the domain I were determined. In this paper, all rearrangements in the main chain were observed upon shifting of C alpha-atoms from 1 to 8 A for each of the three protein domains. It was shown that these changes occur in numerous regions. New regions of changes were found, and they were located mostly in the loops of protein domains. Some of them are in the regions of interdomain interactions, others correlate with the known functionally important regions of EF-Tu binding with EF-Ts, aminoacyl-tRNA and the ribosome. Most changes induced by the conformational signal transfer from the guanosine-3'-triphosphate binding site occur just in the regions that are important for further stages of the factor functioning. The signal is transferred from domain I to domains II and III via interdomain contacts, predetermining fine fitting of functionally important regions to be involved in the following stages of the elongation cycle. The greatest part of the detected changes occurs in conservative residues of the whole family of bacterial factors, and only some of them are specific. This approach may prove useful for predetermining potential functionally important sites in other proteins. PMID- 11771277 TI - [Inactivation of the human thyroid peroxidase by ultrasound cavitation]. AB - The inactivation kinetics of a human thyroid peroxidase protein fraction upon sonication (ultrasound frequency 27 kHz, power 60 W/cm2) of the enzyme solution in 15 mM phosphate buffer, pH 7.5, was studied. To quantitatively characterize the dependence of the slowest stage of the human thyroid peroxidase inactivation on temperature (36.0-50.4) degrees C, an effective constant of ultrasound inactivation rate Kin(US) was used. From the temperature dependence of Kin(US) at temperatures below 43 degrees C, the activation energy was estimated to be 8.11 kcal/mol. It was shown that the rate of human thyroid peroxidase inactivation strongly depends on the concentration of total protein in solution: the kin(US) value decreases more than sixfold in the protein concentration range from 0.2 to 0.8 mg/ml. It was also shown that poly(2-aminodisulfide-4-nitrophenol), its complexes with human serum albumin as well as the complexes human serum albumin- poly(gallic acid disulfide) substantially inhibit the ultrasound-induced inactivation of the enzyme and can be its effective stabilizers in the ultrasound cavitation field. This confirms the suggestion that active free radicals HO., O2. and HO2. play a key role in the inactivation of human thyroid peroxidase. A general scheme of the inactivation of human thyroid peroxidase is proposed, which represents a chain of successive and parallel reversible and irreversible elementary steps. PMID- 11771278 TI - [The use of various models of biosynthesis kinetics]. AB - The available models of the microorganism growth kinetics are analyzed. The possibility of application of the Monod model is studied. It is shown that these models do not permit describing adequately the experimental data at different initial concentrations of biomass and substrate that vary in a wide range. The calculations of the static modes of operation of biochemical react ors differ greatly. PMID- 11771279 TI - [Study of fractal properties of single ionic channel gating mechanism by the fast Fourier transform]. AB - Sets of the channel open times (tau o), closed times (tau c) and the full set of the channel open and closed times (tau o, tau c) in the activity of single Ca(2+) activated K+ channels in cultured kidney cells Vero were analyzed using the fast Fourier transform. It was found that in the low-frequency range (about 0.01-10 Hz), power density can be described by the equation S(f) approximately f-alpha (as a rule, 0 < alpha < 1), and this part of the Fourier spectrum usually consists of narrow peaks at almost multiple frequencies. It was shown that the upper frequency boundary of this spectrum is determined by the kinetic parameters tau o [symbol: see text] tau c. The data obtained show that ion channel gating is a fractal process (correlated in time) and can be regarded as a random signal modulated by some periodical functions (sinuses). The data obtained by the Fourier method are in agreement with the earlier results obtained using the rescaled-range analysis. PMID- 11771280 TI - [The surface membrane potential in a fluctuating medium]. AB - Fluctuations of the surface membrane potential due to adsorbtion and desorbtion of ions when environmental fluctuations generate a fluctuation in the number of adsorbtion sites were investigated. The correlation functions of surface charge density, surface potential and the spectral density of surface potential fluctuations were calculated. The characteristic features of these fluctuations were determined. PMID- 11771281 TI - [Effect of high magnesium ion concentration on the electron transport rate and proton exchange in thylakoid membranes in higher plants]. AB - The effects of magnesium ion concentration on the rate of electron transport in isolated pea thylakoids were investigated in the pH range from 4.0 up to 8.0. In the absence of magnesium ions in the medium and in the presence of 5 mM MgCl2 in the experiments not only without added artificial acceptors but also with ferricyanide or methylviologen as an acceptor, this rate had a well-expressed maximum at pH 5.0. It was shown that, after depression to minimal values at pH 5.5-6.5, it gradually rose with increasing pH. An increase in magnesium ion concentration up to 20 mM essentially affected the electron transfer rate: it decreased somewhat at pH 4.0-5.0 but increased at higher pH values. At this magnesium ion concentration, the maximum rate was at pH 6.0-6.5 and the minimum, at pH 7.0. Subsequent rise upon increasing pH to 8.0 was expressed more sharply. The influence of high magnesium ion concentration on the rate of electron transport was not observed in the presence of gramicidin D. It was found that without uncoupler, the changes in the electron transfer rate under the influence of magnesium ions correlated to the changes in the first-order rate constant of the proton efflux from thylakoids. It is supposed that the change in the ability of thylakoids to keep protons by the action of magnesium ions is the result of electrostatic interactions of these ions with the charges on the external surface of membranes. A possible role of regulation of the electron transport rate by magnesium ions in vivo is discussed. PMID- 11771282 TI - [Effect of R plasmid on cell membrane structure in Salmonella derby]. AB - The structure of membranes of Salmonella derby cells both containing R-plasmid and free of plasmid was studied by small- and large-angle X-ray diffraction. Reflections with interplane distances of 8 and 11 A were detected, which are typical of plasmid-carrying S. derby cells. These reflections are assumed to be due to equidistant well ordered positions of the polar groups of phosphatidylcholine and phosphatidylethanolamine molecules on membrane surface. It is also suggested that the formation of these structures is determined by peculiar hydrophilic-hydrophobic interactions of the phospholipid in membranes. PMID- 11771283 TI - [Effect of urea on conformational changes in the active site of native and reconstituted Ca-ATPase of the sarcoplasmic reticulum]. AB - The effect of urea (1-3 M) on conformational changes in the active center of native and reconstituted Ca-ATPase of sarcoplasmic reticulum modified by fluorescein-5-isothiocyanate (FITC) was studied using the method of fluorescence titration by neodymium (Nd3+) ions. Based on the analysis of curves of fluorescence quenching of FITC-labeled Ca-ATPase by Nd3+ ions, the parameters characterizing the structural changes in the Mg-ATP binding center were determined. It was assumed that FITC and Nd3+ ion bind to different polypeptide fragments moving relative to each other, which provides the conformational lability of the nucleotide binding site at some stages of the catalytic cycle. A comparison of structural changes caused by urea at the active site of native and reconstituted Ca-ATPase of sarcoplasmic reticulum indicates that the Nd3+ binding center is localized in the region of contacts of monomers in the oligomer. PMID- 11771284 TI - [Effect of hypothermia on Na(+)-K(+)-ATPase activity and hemoglobin binding in the rat erythrocyte membranes]. AB - The activity of Na+/K(+)-ATPase and hemoglobin binding in membranes of rat erythrocytes during hypothermia (20 degrees C) was studied. Hypothermia causes an increase in hemoglobin binding and a decrease in Na+/K(+)-ATPase activity. It was found in in vitro experiments that the addition of hemoglobin to the membranes does not affect the Na+/K(+)-ATPase activity in control animals and decreases the activity of the enzyme in hypothermia. PMID- 11771285 TI - [Degranulation of skin mast cells caused by high frequency electromagnetic irradiation of low intensity]. AB - It was shown by light and electron microscopy that local exposure of the projection of the MC-8 lao-gun acupuncture point in rat pad to low-intensity (0.05 mW/cm2) extremely high-frequency (42.0 GHz) electromagnetic radiation caused a degranulation of derma mast cells. It was suggested that the response of skin mast cells is an important amplifying mechanism in the chain of events leading to a systemic response of the organism to low-intensity electromagnetic radiation. PMID- 11771286 TI - [Structural and functional changes in various cells following radiation exposure]. AB - Structural and functional changes in thymocytes, splenocytes and hepatocytes, taking place under gamma-irradiation of cellular suspensions were investigated. It was found that splenocytes begin to lose their functional activity and structural features at a dose of 2 Gy. Increasing the irradiation dose leads to the acceleration of these processes. Thymocytes lose rapidly their functional activity at 2 Gy, but they maintain their structure and membrane parameters even after irradiation with a dose of 10 Gy. In comparison with other cell types, hepatocytes exhibit the greatest stability under the influence of gamma radiation. PMID- 11771287 TI - [Discrete wave mechanism of integral activity in heterogenic neuron synapses]. AB - On the basis of the conception of the discrete wave mechanism for the integration of heterogeneous neuron elements, a hypothesis was put forward that neuron excitation propagates as waves of changes in the conformational states of neuron membrane lipids. A mathematical model was constructed, which confirms the wave mode of excitation propagation. The model enables one to consider the integration of postsynaptic potentials as a process of wave interference. It was assumed that the training of neuron elements can be considered as a process of nonuniform distribution of lipids. PMID- 11771288 TI - [Model of generation and propagation of impulses in neurons]. AB - A model for the generation and propagation of impulses in nervous tissues was developed. The dynamic properties of the model were studied by analytic and quantitative-analytical methods. PMID- 11771289 TI - [Myocardial electrodynamics during electrical systole]. AB - A dipole equivalent generator of heart is considered, which represents a circuit containing an active, capacitive and inductive resistance. The model makes it possible to solve a direct diagnostic task for the electric systole. A differential equation for the integral electrical vector of the heart in the dipole approximation was solved. A model vector electrocardiogram and a linear electrocardiogram for the electrical heart parameters are presented. PMID- 11771290 TI - [Extremely high frequency dielectrometry of biological fluids under conditions of disturbed water balance]. AB - The electrical properties of fractions of blood, B-bile, and aqueous ethanol solutions were studied by UHF dielectrometry. A relationship between the electric permittivity of these biological liquids at a frequency of 62 GHz and their functional value was established. The changes in the electrical characteristics of the solutions in some disturbed functional states were explained by the rebuilding of water quasicrystaalline structure. PMID- 11771291 TI - [Characteristics of low frequency magnetic field effect on swelling of wheat seeds at various stages]. AB - Low-frequency magnetic field treatment (50 Hz, 30 mT, 15 min) of wheat seeds with a 50% germination efficiency during imbibition at the stage of root formation leads to a statistically significant increase in the number of seeds having sprouts, a still greater increase in the number of seeds having roots, and to an increase in the length of sprouts compared with the control and the seeds treated several hours later. In the last case, an increase in the germinating capacity with a considerably lesser effect on the number of seeds with roots was also observed. Prolonged treatment with the field during the second day of imbibition decreased reliably the length of sprouts with a weaker influence on the number of seeds with sprouts and roots. These data suggest the principal possibility of the effect of electromagnetic fields on the realization of the genetic program during the germination of wheat seeds. PMID- 11771292 TI - [Forecasting of biocenosis quantity in the open system with a finite difference model]. AB - A simple mathematical model for the dynamics of biocenosis in an open system was worked out. The model is based on the finite-difference presentation of experimental data. It also takes into account the past history of population development. The testing of the model proved its ability to forecast the density of populations in open systems. PMID- 11771293 TI - [The role of biosphere in the formation of the Earth climate. A greenhouse catastrophe]. AB - The role of processes in organic and inorganic nature that determine the formation of the atmosphere chemical composition and Earth temperature balance was analyzed. It was concluded that the biological mechanisms of CO2 removal from the atmosphere are insufficient, and there exist potentially hazardous CO2 sources in inorganic nature that can be activated upon elevation of the mean Earth temperature. It was shown that the stability of natural systems of maintaining the constant chemical composition of the atmosphere is destroyed due to the disturbance by man of climate-forming biocenoses, which may lead to irreversible changes in Earth's climate with the result that the mean planetary temperature would be elevated to 100-150 degrees C and above. This would make impossible the existence of life on our planet, at least in its present form. A radiation-adiabatic model of the greenhouse effect was constructed in the framework of which asymptotic estimates of the increase in mean planet temperatures for a wide range of changes in the concentration of greenhouse gases were obtained. On the basis of the model, an integral model of changes in Earth's climate was constructed, which takes into account the heat inertia of the ocean and aerosol contaminations of the upper layers of the atmosphere. It was shown that irreversible (catastrophic) changes in Earth's climate (greenhouse catastrophe) may occur in a relatively near future (200-300 years). PMID- 11771294 TI - [Apoptosis dynamics in human neutrophils induced by ultraviolet C irradiation during lipopolysaccharide and zinc exposure]. AB - The action of ultraviolet radiation with lambda = 254 nm (UVC), zinc and lipopolysaccharide on the apoptosis of human neutrophils was investigated by flow cytometry. It was shown that zinc (0.2-1 mM) inhibits the UVC-dependent acceleration of neutrophil apoptosis. Preliminary treatment with UVC cancels the inhibition of neutrophil apoptosis by lipopolysaccharide. PMID- 11771295 TI - [Double and bifurcated hydrogen bonds in alpha-helices of globular proteins]. AB - The statistical analysis of hydrogen bonds distribution in space structures of globular proteins has been done. The parameters of H-bonds in the different secondary structures of globular proteins were collected. In alpha-helices besides the canonical 1-5 H-bonds (the mean length 3 A), 1-4 H-bonds were observed (the mean length 3.2 A). The histograms of length and angular distributions of the bonds are presented. It was found on the basis of quantum chemistry calculations that most H-bonds in alpha-helices are double or bifurcated. PMID- 11771296 TI - [Intrinsic UV-fluorescence of lysozyme and microenvironment of its tryptophan residues]. AB - The localization of tryptophan residues in hen egg-white lysozyme macromolecule was studied on the basis of the known 3D structure. The polarity and packing density of their microenvironments were evaluated. All residues that can affect the tryptophan fluorescence were revealed. It was shown that the orientation of these active groups relative to the indole ring of tryptophan plays a dramatic role in the efficiency of their influence. Tryptophan--tryptophan nonradiative energy transfer was evaluated from distances between tryptophan residues and their mutual orientation. The conformation of the side chains of tryptophan residues was determined. Special attention was paid to microenvironment of Trp108 responsible for the minor absorption band at 305 nm. PMID- 11771297 TI - [Tryptophan phosphorescence of nascent and inactivated actin at the room temperature]. AB - Millisecond internal dynamics of native and inactivated actin from rabbit skeletal muscle was examined using room temperature phosphorescence. Inactivated actin was prepared by incubation of G-actin at 70 degrees C, by treatment with 4 M urea or 1.5 M guanidinium hydrochloride, renaturation from fully unfolded state or by Ca2+ ion removal. It was shown that inactivation of actin, irrespective of the denaturation procedure applied, leads to a sharp decrease of millisecond fluctuations of the protein structure. Restriction of the slow intramolecular mobility in inactivated actin can result from changes of the protein conformation and/or specific association of macromolecules. PMID- 11771298 TI - [Energetics of hydratation of nucleic acids with various nucleotide composition]. AB - The hydration energetics of natural DNA with various AT/GC-composition and model double-helix polyribonucleotides was studied using a new approach which is based on calorimetric measurements of the dehydration energy of nucleic acid-water systems at various levels of relative humidity. A linear correlation between the dehydration energy and the nucleotide composition of natural DNA was found. PMID- 11771299 TI - [Nuclear genetic material as an initial substrate for animal aging]. AB - General properties of aging in animals are considered on the basis of the literature evidence and the results obtained by the authors of this paper. The existence of a specific aging mechanism is inferred. The operation of this mechanism is controlled not only by genes but also by particular noncoding genomic sequences with variable structure. The beginning of senescence in animals is determined by DNA lesions located in neural cells and probably in a minor genomic fraction. The authors refute the narrow concept of aging as a mechanism increasing the probability of death. Mortality as a continuous process occurring with the probability of 100 percent is an integral attribute of living organisms on the Earth. PMID- 11771300 TI - [Tissue-specific placental mosaicism for autosomal trisomies in spontaneous human abortuses: mechanisms of formation and phenotypic effects]. AB - The frequencies of autosomal trisomies in extraembryonic human tissues were estimated in the cases of different abnormalities of prenatal development, from the confined placental mosaicism (CPM) with either relatively normal embryogenesis or restricted intrauterine growth to spontaneous abortion. A tissue specific compartmentalization was found to be characteristic of cell lines with trisomies for individual autosomes. Analysis of various phenotypical effects of chromosomal aberrations associated with mosaicism is necessarily required to understand the mechanisms and factors responsible for tissue chromosomal mosaicism. Based on analysis of the cell karyotype during prenatal diagnosing of chromosome aberrations in tissues of both extraembryonic and embryonic origin, in 1996, Wolstenholme proposed a model of CPM for individual chromosomes. According to the model, the distribution of cell lines with autosomal trisomies between extraembryonic tissues depends on the ratio between meiotic and mitotic mutations early in embryonic development. However, the model cannot be used to study tissue chromosomal mosaicism in spontaneous abortions, because little information is available on cell karyotype in embryonic tissues themselves after intrauterine fetal death. In this work, a model of tissue-specific chromosomal mosaicism was suggested based on the data on cell karyotype determined in extraembryonic tissues alone, which can be helpful in evaluating the contribution of tissue chromosomal differences into the etiology of early intrauterine death. Along with the experimental evidence, comparative analysis of the two models indicated that the meiotic chromosome nondisjunction plays the major role in trisomy formation and the resultant spontaneous arrest of embryonic development. Other factors responsible for tissue-specific distribution of chromosomal aberrations are also discussed. These are differences in cell proliferative activity, as well as changes in compartmentalization and migration of cells with abnormal karyotypes. PMID- 11771301 TI - [Genetic control of hormonal regulation of sex differentiation and development of the human reproductive system]. AB - Literature data on genetic control of hormonal regulation of sexual differentiation and reproduction system development in humans are reviewed. The conditions caused by mutations of genes for gonadoliberin, gonadotorpin, and anti Mullerian hormone, as well as genes controlling biosynthesis of sexual steroids and the receptors for the latter, are considered. PMID- 11771302 TI - [Analysis of DNA interband regions 3A5/A6, 3C5-6/c7 and 60E8-9/E10 of Drosophila melanogaster polytene chromosomes]. AB - Using electron microscopic (EM) data on the formation of a novel band from the P element material after its insertion in the interband and the procedure of P target rescue, DNA interband regions 3A5/A6, and 60E8-9/E10 of Drosophila melanogaster polytene chromosomes were cloned and sequenced. EM analysis of the 3C region have shown that the formation of the full-size 3C5-6/C7 interband requires a 880-bp DNA sequences removed by deletion Df(1)faswb. A comparison of DNA sequences of six bands, two of which were obtained in the present work and four were described earlier, demonstrated the uniqueness of each of them in the Drosophila genome and heterogeneity of their molecular organization. Interband 60E8-9/E10 contains gene rpl19 transcribed throughout the development, in particular in salivary glands. In the other interbands examined 5' and 3' nontranslated gene regions are located. These results suggest that Drosophila interbands may contain both housekeeping genes and regulatory sequences of currently inactive genes from adjacent bands. PMID- 11771303 TI - [ARS-activity of a DNA fragment from Bombyx mori in Saccharomyces cerevisiae cells]. AB - A previously cloned autonomous transgene (pr8a) of silkworm Bombyx mori inherited without changes in the structure was used to clarify the activity of its ARS in yeast cells. ARS of pr8a was also shown to maintain autonomous replication of hybrid plasmids in yeast cells. The same was true for its central 2.4-kb fragment devoid of flanking sequences. PMID- 11771304 TI - [Analysis of various types of competition in Tn5-mutants of alfalfa rhizobium bacteria (Sinorhizobium meliloti)]. AB - Nodulation, rhizospheral, and saprophytic types of competitiveness (NC, RC, and SC, respectively) were studied in the highly active strains CXM1-105 and CXM1-188 of the alfalfa rhizobium Sinorhizobium meliloti. The competitiveness was estimated with the use of markers of antibiotic resistance. It was found that the mutant strain T37, which was characterized by a drastically decreased NC, had higher SC and RC than the parental strain. The mutant T107 (with a moderately decreased NC) did not differ from the parental strain with respect to RC but had a higher SC. The mutant T27 (with the lowest NC) did not differ from the parental strain with respect to SC or RC. In the mutant Tb1, the NC and RC were decreased and the SC was the same as in the parental strain. In Tb7, the SC was decreased and RC was increased. In the mutant T795, all of the three types of competitiveness were decreased. The difference between the mutants studied and the parental strain with respect to NC and RC was confirmed using an indirect method (the ability to form effective symbiosis after mixed inoculation together with the an ineffective tester strain CXM1-48) and the X-Gluc staining method (using the S. meliloti RmM4gus tester strain carrying the gene of beta glucuronidase). However, the decreased SC that the mutants exhibited when they were cultivated together with parental strains in a plant-growth substrate (vermiculite) was not observed in the case of their cocultivation in liquid media. The independent variation of different types of competitiveness indicate that rhizobia have several separate gene systems determining their survival in in planta and ex planta ecological niches. PMID- 11771305 TI - [Some behavioral features in Drosophila melanogaster lines carrying a flamenco gene mutation]. AB - Olfactory sensitivity and locomotor activity was assayed in Drosophila melanogaster strains carrying a mutation of the flamenco gene, which controls transposition of the mobile genetic element 4 (MGE4) retrotransposon the gypsy mobile element. A change in olfactory sensitivity was detected. The reaction to the odor of acetic acid was inverted in flies of the mutator strain (MS), which carried the flam mutation and active MGE4 copies and were characterized by genetic instability. Flies of the genetically unstable strains displayed a lower locomotor activity. The behavioral changes in MS flies can be explained by the pleiotropic effect of the flam mutation or by insertion mutations which arise in behavior genes as a result of genome destabilization by MGE4. PMID- 11771306 TI - [Level of phytohormones in various types of symbiotic pea mutants]. AB - The levels of the phytohormones auxin and gibberellin were studied in the original pea (Pisum sativum L.) cultivars Rondo and Ramonskii 77 and in different types of symbiotic mutants (non-nodulating, with single nodules, and supernodulating) induced from them. The results obtained indicated that the levels of the phytohormones in the symbiotic mutants depend on the plant's genotype, developmental phase, and infection with rhizobia. Two mutants were isolated whose phytohormonal statuses markedly differed from the original forms. These mutants may be used for identification of the genes that determine the auxin and gibberellin statuses. PMID- 11771307 TI - [Uniformity of distributing alleleic variants of three hordein-coding loci of spring barley in the Russian Federation]. AB - The distribution of alleles of the hordein-coding loci Hrd A, Hrd B, and Hrd F was investigated in 101 spring barley cutivars grown in 12 regions of Russia in 1999. It was demonstrated that the genetic structure of populations of these cutivars in the regions studied was affected by climatic factors, such as the average June temperature and average annual precipitation. The distribution patterns of the Hrd alleles in 25 agricultural provinces of the former Soviet Union and 12 regions of Russia were compared. The factor structure of genetic variability in the regions of barley cultivation in the former Soviet Union was found to differ from that in Russia. The change of the factor structure is likely to be related to diminishing the barley-production area under study and to the new administrative subdivision. PMID- 11771308 TI - [Transcription map of the 13q14 region, frequently deleted in B-cell chronic lymphocytic leukemia patients]. AB - Deletions in the region located between the STS markers D13S1168 and D13S25 on chromosome 13 are the most frequent genomic changes in patients with B-cell chronic lymphocytic leukemia (B-CLL). After sequencing of this region, two novel candidate genes were identified: C13orf1 (chromosome 13 open reading frame 1) and PLCC (putative large CLL candidate). Analysis of the repeat distribution revealed two subregions differing in composition of repetitious DNA and gene organization. The interval D13S1168-D13S319 contains 131 Alu repeats accounting for 24.8% of its length, whereas the interval GCT16C05-D13S25, which is no more than 180 kb away from the former one is extremely poor in Alu repeats (4.1% of the total length). Both intervals contain almost the same amount of the LINE-type repeats L1 and L2 (20.3 and 21.24%, respectively). In the chromosomal region studied, 29 Alu repeats were found to belong to the evolutionary young subfamily Y, which is still capable of amplifying. A considerable proportion of repeats of this type with similar nucleotide sequences may contribute to the recombinational activity of the chromosomal region 13q14.3, which is responsible for its rearrangements in some tumors in humans. PMID- 11771309 TI - [Pedigree analysis in evaluating gene frequency in aboriginal populations of Siberia]. AB - Procedure is described to estimate allele frequencies in indigenous populations of Siberia using phenotype data not only for "pure-blood" representatives of the ethnic groups examined, but also for the descendants of mixed marriages. Implementation of the method requires reconstruction of the data on relatives for the sample examined. Inclusion of the data on descendants of mixed marriages into the analysis increases the sample information content and decreases variance of the estimates obtained. The advantages of the method are illustrated using an example of Tundra Nentsy, for whom it was shown that variance of estimates at the analysis of the blood groups allele frequencies can be diminished approximately by a factor of 1.5. PMID- 11771310 TI - [Reverse in situ hybridization of DNA probes of anomalous chromosomes in diagnosing chromosome pathologies]. AB - The results of analysis of congenital chromosomal pathologies and chromosomal rearrangements upon the occurrence of haematological diseases, which was involved constructing DNA libraries of abnormal chromosomes and subsequent reverse CISS hybridization have been considered. High effectiveness of this approach for analysis of chromosomal translocations, deletions of chromosomal regions, minor extra chromosomes, and large marker chromosomes with complex organization was shown. The possibility of implementation of this approach and its large-scale application in medical and genetic studies of congenital developmental pathologies and chromosomal diagnostics of haematological diseases has been discussed. PMID- 11771311 TI - [Analysis of Alu-polymorphism in Buryat populations]. AB - Polymorphism of three populations of the Buryat Republic and a population from Aginskii Buryat Autonomous okrug of Chita oblast was examined using a set of five autosomal Alu insertions at the ACE, PLAT, PV92, APOA1, and F13B loci. The allele frequency distribution patterns revealed in Buryat populations were typical to other Asian populations. Buryats were characterized by relatively low level of intrapopulation diversity (0.369 in the pooled population sample). Analysis of autosomal Alu insertions suggests the uniformity of the Buryat gene pool. The coefficient of genetic differentiation in the four populations studied was 0.8%. PMID- 11771312 TI - [Analysis of diversity of autosomal-recessive diseases in Russian populations]. AB - The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected subjects was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1:50,000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1:877,483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (Fst) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (Fst) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift. PMID- 11771313 TI - [Genetic polymorphism of blood group and erythrocyte enzymes in three ethno territorial groups of the northern European part of Russia]. AB - Using the data on five red cell markers (AB0, PGM1, ACP1, GLO1, and ESD) polymorphisms, the population genetic structure of three ethnic territorial groups from the north of European Russia (Continental Nentsy, Kola Saami, and Russian Coast-dwellers) was described. In general, the groups studied a Caucasoid pattern of the frequency distribution of erythrocytic marker alleles. However, a substantial contribution of a Mongoloid component to the Nenets gene pool, expressed as a high frequency of the PGM1*1 allele along with a low frequency of the GLO1*1 allele, was observed. Three ethnic territorial groups examined were close to one another with respect to the distribution of classical biochemical markers. The interpopulation diversity was low (the mean FST = 0.015). The differences observed were for the most part caused by the genetic characteristics of Nentsy. The maximum interpopulation diversity was observed for the GLO1 locus (FST = 0.056). PMID- 11771314 TI - [T4336C variant--a marker of mitochondrial subgroup H1, a common component of the Russian and German gene pool]. AB - Analysis of mitochondrial DNA (mtDNA) restriction polymorphism carried out in a sample of Russians from Magadan (n = 150) showed that the frequency of the +4332AvaII variant (a T-C transition at nucleotide position 4336) in this population was 4.7%. All +4332AvaII types of mtDNA belonged to the mitochondrial group H. They were characterized by a back of the AluI restriction endonuclease site at position 7025. According to hypervariable segment 1 sequencing data, they contained the 16304C variant, and thus belong to the subgroup H1. Thus, the +4332AvaII (T4336C) variant is a marker of the mitochondrial subgroup H1, chiefly occurring in German-speaking populations. Utilization of the H1-mtDNA markers for the investigation of the genetic history and the origin of Slavs is discussed. PMID- 11771315 TI - [Polymorphism of the serotonin 2A receptor gene in populations from the Volga Ural region]. AB - The MspI restriction polymorphism of the serotonin 2A receptor gene (5HT2A) was typed in populations of the Volga-Ural region (Bashkirs, Chuvashes, Tatars, Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of Bashkortostan). Population-specific patterns of the main polymorphism indices distribution were established. Specific trends in the changes of genotype and allele frequency of the 5HT2A gene depending on the ethnicity of the population were revealed. PMID- 11771316 TI - [Plant proteinase inhibitors as polyfunctional proteins (a review)]. AB - Literature data on plant proteinase inhibitors as multifunctional proteins are reviewed. In addition to the direct inhibitory effect on enzymes, these proteins may function in other processes, particularly under biotic and environmental stressful conditions. A special section discusses the relationships of plant proteinase inhibitors and storage proteins. PMID- 11771317 TI - [Formation of wine aroma: tones and imperfections caused by minor components (a review)]. AB - Mechanisms of formation of primary and secondary wine aroma and processes associated with wine maturation and ageing are reviewed. Compounds determining brand- or technology-specific aroma tones (floral, fruit, honey, black-currant, nightshade, yeast, oak-cask, thermal, etc.) are identified. Chemical background of unacceptable, foul tones (oxidized, murine, acetic, hydrogen-sulfide, saprogenic, cabbage, hospital, mold, vulpine, etc.) is presented. PMID- 11771319 TI - [Characteristics of Triticale glutaminase]. AB - The glutaminase (EC 3.5.1.2) isolated from seedlings of triticale (Triticale sp.) had a pH optimum of about 8, was inhibited with excess substrate (glutamine), and reaction products (glutamate and NH4+). A monovalent anion (Cl-) and a multivalent anion (phosphate) were shown to activate the glutaminase. Some features of the glutaminase from triticale were similar to those of animal glutaminase activated by phosphate and were different from features of the enzyme from Escherichia coli. PMID- 11771318 TI - [Biosynthesis and use of coproporphyrins and uroporphyrins and their metal complexes in immune analysis and diagnostic methods]. AB - Methods of synthesis of coproporphyrin and uroporphyrin by using bacteria of the genus Arthrobacter are proposed. Metal complexes of coproporphyrin and uroporphyrin with Pt, Pd, and Zn were synthesized. Their structures were identified by spectrophotometry, IR spectrometry, 1H-NMR, mass spectrometry, and HPLC. Data showing the possibility to use coproporphyrin III-metal complexes as luminophores for fluorescence detection of tumors. The current and prospective uses of metal complexes of water-soluble natural porphyrins in advanced immunofluorescence assays are discussed. PMID- 11771320 TI - [Purification and characteristics of alkaline proteinase from alkalophylic Bacillus sp]. AB - Alkaline protease was purified from Bacillus sp. isolated from soil. The pH optimum was 11.5 at 37 degrees C. Calcium divalent cation was effective to stabilize the enzyme especially at higher temperatures. The proteolytic activity was inhibited by active site inhibitors of PMSF (Phenylmethylsulfonyl fluoride), and ions of Mg, Mn, Pb, Li, Zn, Ag, Hg. The enzyme was stable in the presence of some detergents, such as Triton-X-100, Tween-80, SDS (sodium dodecyl sulfate) and EDTA (ethylendiaminetetraacetic acid), pH 11.5 and 37 degrees C for 30 min. The optimum pH was 11.5 at 37 degrees C and the optimum temperature was 62 degrees C at pH 11.5. PMID- 11771321 TI - [Thermal stability of Penicillium adametzii glucose oxidase]. AB - The thermal stability of glucose oxidase was studied at temperatures between 50 and 70 degrees C by kinetic and spectroscopic (circular dichroism) methods. The stability of glucose oxidase was shown to depend on the medium pH, protein concentration, and the presence of protectors in the solution. At low protein concentrations (< 15 micrograms/ml) and pH > 5.5, the rate constants kin (s-1) for thermal inactivation of glucose oxidase were high. Circular dichroic spectra suggested an essential role of beta structures in stabilizing the protein globule. At a concentration of 15 micrograms protein/ml, the activation energy Ea of thermal inactivation of glucose oxidase in aqueous solution was estimated at 79.1 kcal/mol. Other thermodynamic activation parameters estimated at 60 degrees C had the following values: delta H = 78.4 kcal/mol, delta G = 25.5 kcal/mol, and delta S = 161.9 entropy units. The thermal inactivation of glucose oxidase was inhibited by KCl, polyethylene glycols, and polyols. Among polyols, the best was sorbitol, which stabilized glucose oxidase without affecting its activity. Ethanol, phenol, and citrate exerted destabilizing effects. PMID- 11771323 TI - [Biosynthesis of pectinase by fungi Bjerkandera and Coriolus by solid phase fermentation]. AB - Production of an extracellular pectinase by wood-rot fungi of the genus Bjerkandera and Coriolus was studied. The active producers B. adusta 40 and C. versicolor 24 were selected. The dynamics of production of pectinase and effects of temperature, initial pH, humidity of the medium and addition of nitrogen sources on the biosynthesis of pectinase were studied. PMID- 11771322 TI - [Isolation and properties of cellobiase from Penicillium verruculosum]. AB - Cellobiase (beta-D-glucosidase) with a molecular weight of 100 kDa and pI 5.2 was isolated from the cellulolytic system of Penicillium verruculosum. Kinetic parameters of enzymatic hydrolysis of cellobiose, gentiobiose, sophorose, and synthetic substrates, i.e. methylumbelliferyl and p-nitrophenyl sugar derivatives were determined. Glucose and D-glucose-delta-lactone competitively inhibited cellobiase (Ki = 0.19 mM and 17 microM, respectively). Glucosyl transfer reactions were studied with cellobiose as a single substrate and in the mixture of cellobiose and methylumbelliferyl cellobioside. The product composition was determined in these systems. The ratio of hydrolysis and transfer reaction rates for cellobiose conversion was calculated. PMID- 11771324 TI - [Insecticidal activity of Bacillus thuringiensis cells]. AB - The influence of sixteen different nutrient media on the entomopathogenic activity of three Bacillus thuringiensis strains was studied. The medium composition based on potato, yeast extract, and molasses was optimized. B. thuringiensis No 1 grown on the media No 7 and 9 displayed the highest entomopathogenic activity (94.3 and 90.6%, respectively). PMID- 11771325 TI - [Search for methanotrophic producers of exopolysaccharides]. AB - Bacteria that produce exopolysaccharides (EPS) and use methane as the only source of carbon were selected by studying a collection of methanotroph strains: Methylococcus capsulatus E 494, 874, and 3009; M. thermophilus 111p, 112p, and 119p; Methylobacter ucrainicus 159 and 161; M. luteus 57v and 12b; Methylobacter sp. 100; Methylomonas rubra 15 sh and SK-32; Methylosinus trichosporium OV3b, OV5b and 4e; M. sporium 5, 12, A20d, and 90v; and Methylocystis parvus OVVP. Mesophilic methanotroph strains with the ribulose monophosphate way of C1 compound assimilation synthesized EPS more actively than bacteria operating the serine cycle. The dynamics of EPS synthesis by methanotrophs during chemostat cultivation was studied. PMID- 11771327 TI - [Inhibition of peroxidase oxidation of 3,3',5,5'-tetramethylbenzidine and o phenylenediamine by 1-amino-2-naphthol-4-sulfonic acid and its polysulfide]. AB - The kinetics of coupled peroxidation of 3,3',5,5'-tetramethylbenzidine and 1 amino-2-naphtol-4-sulfonic acid (ANSA) or its polydisulfide (poly(ADSNSA)) was studied in 0.01 M phosphate buffer (pH 6.4) at 20 degrees C. Both ANSA and poly(ADSNSA) strongly inhibited the TMB oxidation resulting in a marked delay in the product formation. Stoichiometric inhibition coefficients f, i.e., the average numbers of free-radical particles terminated by one inhibitor molecule, were estimated. The free-radical trapping effect of poly(ADSNSA) was 7.5 times greater than that of ANSA. Kinetics of coupled o-phenylenediamine (PhDA) and ANSA or poly(ADSNSA) oxidation was studied in phosphate-citrate buffers at pH 3 to 7. No lag periods in oxidation product accumulation were observed under any of the reaction conditions. A weak activation of PhDA conversion depending on pH and PhDA/ANSA ratios was observed at low ANSA concentrations, whereas increased ANSA or poly(ADSNSA) concentrations were inhibitory. The degree of PhDA inhibition was maximal in acid media, reached minimum at pH 5 to 6, and than again increased at pH above 6. Tentative mechanism of coupled aromatic amine phenol bi-substrate system peroxidation is discussed. PMID- 11771326 TI - [Activity of carbon metabolism enzymes in wheat plants treated with kartolin-4 and exposed to water stress]. AB - Enzymatic activities of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (EC 4.1.1.39), phospho(enol)pyruvate carboxylase (EC 4.1.1.31), NAD malate dehydrogenase (EC 1.1.1.37), and NADP glyceraldehydephosphate dehydrogenase complex including phosphoglycerate kinase (EC 2.7.2.3) and glyceraldehydephosphate dehydrogenase (EC 1.2.1.13) were comparatively assayed in wheat seedlings of the cultivar Lyutestsens 758 grown under normal conditions, water deficiency conditions, and subsequent rehydration. Water stress was found to decrease the activity of all enzymes tested, the effect being most pronounced in case of Rubisco. The content of Rubisco in wheat plants exposed to water deficiency was reduced less significantly than the activity of the enzyme. Preliminary treatment of plant seeds with kartolin-4 (o-isopropyl-N-2 hydroxyethyl carbamate), a preparation with cytokinin activity, reduced the dehydration-induced inhibition of enzymatic activity. Upon a subsequent rehydration, kartolin-4 facilitated rapid recovery of the photosynthetic activity, the process being based on the kartolin-induced stimulation of reparation reactions. Under conditions of water stress, a partial decrease in the activity of carbon metabolism enzymes in vitro was accompanied by complete inhibition of photosynthesis in vivo, perhaps, as a result of an abrupt increase in the stomatal resistance. PMID- 11771328 TI - [Ethylene-induced activation of xylanase in adventitious roots of maize as a response to the stress effect of root submersion]. AB - Submersion of roots of ten-day-old maize (Zea mays L.) seedlings was accompanied by a decrease in pO2 and an increase in pCO2 of the medium adjacent to roots. These changes stimulated ethylene evolution in intact plants. Enhanced biosynthesis of ethylene was accompanied by xylanase activation in adventitious roots. As a result, an enhanced formation of aerenchyma was observed in the cortex of adventitious roots. Therefore, these processes resulted in the development of a ventilation system by which O2 can reach the root system exposed to hypoxia. The volume of aerenchyma was assessed by the volume of gas cavities (porosity). In contrast to the main root, the growth of adventitious roots was not inhibited under these conditions. Enlargement of the stem base and increase in the number of aerenchymatous adventitious roots facilitated the oxygen supply to submerged organs of plants. PMID- 11771329 TI - [Effect of conditions and duration of storage on composition of essential oil from coriander seeds]. AB - The composition of volatile components of the essential oil extracted from seeds of coriander (Coriandrum sativum L.) grown in different years in either Russia or Georgia was studied by capillary gas chromatography. Climatic conditions had a weaker effect on the essential oil composition than the region of growth. After one-year storage in the dark, minor changes were observed in the oil composition, and its organoleptic properties were virtually unchanged. However, the essential oil underwent significant chemical transformation of monoterpenes when stored in the light. PMID- 11771330 TI - [The use of chitosan solutions for defatting and clarification of protein hydrolysates]. AB - The possibility of the use of small amounts of chitosan for defatting and clarification of protein solutions prepared by enzymatic hydrolysis was tested. The following treatment conditions were shown to be optimal: chitosan concentration range, from 1.0 to 1.5 g per kg raw weight; pH of precipitation medium, from 8.0 to 8.5; and duration of incubation of protein hydrolysate solution with chitosan, less than 1 h. The hydrolysate defatting grade was found to depend on the degree of chitosan deacetylation. A possible mechanism of the chitosan-induced effects was suggested. The use of chitosan allows the mass fraction of enzyme protein hydrolysates to be reduced fourfold to fivefold. PMID- 11771331 TI - [Kinetic method of tungsten analysis in tungsten-containing enzymes]. AB - A highly sensitive method for tungsten detection in proteins based on the ability of this metal to catalyze the oxidation of with hydrogen peroxide is described. The method allows determining tungsten in protein samples in the concentration range of -0.05 to -0.4 microgram/ml. Molybdenum, at a concentration lower than half the concentration of tungsten, as well as iron, selenium, and pterin at concentrations -2.5 times higher than that of tungsten, had no effect on tungsten determination by this method. PMID- 11771332 TI - [Interaction of E. coli cells with ascorbic acid and sodium nitrite studied by ESR method]. AB - Ascorbic acid, an effective modulator and regulator of cell metabolism, was shown to induce the production of nitric oxide in E. coli cells. This process was detected by EPR spectroscopy as the generation of a spectral signal typical of nitrosyl-iron-sulfur centers (Fe-S-NO) under anaerobic conditions. Incubation of E. coli cells in the presence of ascorbic acid under aerobic conditions was shown to be accompanied by sodium nitrite formation. It is suggested that ascorbic acid is capable of supporting the system of energy supply to cells in hypoxia caused by reduced oxygen content or treatment with sodium nitrite. PMID- 11771333 TI - [The 4th International Seminar-Presentation of Innovative Scientific and Technical Projects "Biotechnology-2000"]. PMID- 11771334 TI - [Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1998 and March 1999]. AB - The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982. This paper describes the results obtained in fiscal 1998 (from April 1998 to March 1999). The number of cases investigated as objectives was 225 for one year. A total of 429 strains (121 strains from primary infections and 308 strains from postoperative infections) were isolated from 183 cases (81.3% of total cases). In primary infections, the isolation rates of anaerobes and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes and Pseudomonas aeruginosa were higher than in primary infections. On the whole, among Gram positive aerobes, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus with high frequency in isolation from postoperative infections. Among Gram-positive anaerobes, Peptostreptococcus spp. and Streptococcus spp. were predominantly isolated. Among Gram-negative aerobes, E. coli, P. aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were frequently isolated. Among Gram-negative anaerobes, Bacteroides fragilis group was the majority of isolates. In primary infections, the percentage of Gram negative aerobes has gradually increased since fiscal 1995 or 1996 with these years as the turning point, while those of Gram-positive and Gram-negative anaerobes have gradually declined. In postoperative infections, the percentage of Gram-negative anaerobes has increased continuously since the mid-1980s. The percentage of MRSA among S. aureus rose to 89.7%, which was the highest level since the beginning of this study. The susceptibilities of B. fragilis, which did not show apparent changes, were recognized to have decreased against cephems in fiscal 1998. Among other bacteria in B. fragilis group, development of resistance to cephems has continued on a long-term basis since the mid-1980s. E. coli and K. pneuminiae have obviously not changed in susceptibilities, however, the susceptibilities of isolated strains in fiscal 1998 against high-generation cephems, oxacephems and monobactams have declined. We found neither vancomycin resistant nor teicoplanin-resistant strains of S. aureus and Enterococcus spp. PMID- 11771335 TI - [Clinical and bacteriological studies of ceftriaxone (CTRX) once daily administration in pediatric patients with respiratory tract infections]. AB - Clinical studies of ceftriaxone (CTRX) were performed at a dose of 40 mg/kg once daily to evaluate its pharmacokinetics, and clinical and bacteriological efficacies in pediatric patients with respiratory tract infections. The following results were obtained. 1. Of 45 patients, clinical responses to CTRX were excellent in 34 (75.6%), good in 9 (20.0%) and poor in 2 (4.4%), indicating the overall efficacy rate of 95.6%. 2. Haemophilus influenzae (23 strains), Streptococcus pneumoniae (20 strains) and Moraxella catarrhalis (17 strains) were isolated from the patients as the main causative organisms. MIC90 of CTRX against these detected bacteria was < or = 0.06 microgram/ml with H. influenzae [beta lactamase (-)/ABPC (S)], 0.25 microgram/ml with H. influenzae (BLNAR), 0.05 microgram/ml with PSSP, 1.0 microgram/ml with PISP/PRSP and 2.0 micrograms/ml with M. catarrhalis, respectively. 3. The eradication rate of causative organisms was 90.0% (27/30). 4. Serum levels of CTRX after administration of a 1-hour intravenous drip infusion of 40 mg/kg were investigated in 12 patients. Mean serum level at 24 hours after the administration was 9.4 +/- 2.8 micrograms/ml, which covered the level of MIC90 throughout the 24 hours. 5. No adverse reactions related to CTRX were observed. As the approved dosage of CTRX in pediatric patients is twice daily, while it is once daily in adults, there have been few reports on the efficacy of once-daily CTRX in pediatrics. According to the results of the study, it is suggested that once-daily CTRX for the pediatric patients with respiratory tract infections is useful. Further studies might be required to establish outpatient parenteral antibiotic therapy (OPAT) in pediatric infections. PMID- 11771336 TI - Hospital preparedness for biological and chemical terrorism in central New Jersey. PMID- 11771337 TI - Bioterrorism. PMID- 11771338 TI - Smallpox at the Morristown encampment. PMID- 11771339 TI - Traumatic brain injury. The silent epidemic. PMID- 11771340 TI - Health illiteracy. Hazardous to quality health care. PMID- 11771341 TI - Benchmarking your practice. AB - A medical practice is a business and as such is governed by the principles of good business management; these include planning, budgeting, and supervision. A benchmark comparison of a practice is the first step in identifying the factors that determine the financial performance of the practice. However, it is only a first step. Performance is also measured against expectations. A benchmark comparison against market data is not the only tool to use in managing a business successfully. Creating a financial budget together with performance standards is essential to developing and maintaining a healthy practice. PMID- 11771342 TI - [This issue of Acta Otorhinolaryngologica Italica]. PMID- 11771343 TI - [Petrous bone cholesteatoma: surgical strategy]. AB - Petrous bone cholesteatoma is a rare pathology which grows slowly and is often asymptomatic. This work presents a series of 25 cases of Petrous bone cholesteatoma and discusses the diagnostic impact, the surgical approach, the results and the complications. Currently our surgical orientation favors translabyrinthine and transcochlear approaches which, better than other ones, allow both radical excision of the lesion and preservation of the main neuro vascular structures. Out of the 25 patients undergoing surgery, 22 were treated with the translabyrinthine (6 cases) or transcochlear (16 cases) approaches, in 1 case an infratemporal type A approach was used while the remaining 2 were treated with a median cranial fossa approach. Paralysis of the facial nerve is the most dreaded complication, particularly when a deficit is already present prior to surgery. In just a few cases did the hearing justify an attempt at preservation but in no case should this compromise radical removal of the cholesteatoma. PMID- 11771344 TI - [Enlarged translabyrinthine approach in large acoustic neurinomas]. AB - The translabyrinthine approach has long been, and in some centers is still, considered inadequate for the removal of large acoustic neuromas (AN). Over the years, with experience, the original technique has been modified, extending the approach to what is now called the enlarged translabyrinthine (ET) approach. Applying these modifications, between April 1987 and February 2000, the Gruppo Otologico in Piacenza, Italy removed 132 ANs, 3 cm or larger, from the cerebello pontine angle. These tumors accounted for 25.9% of the 510 cases of AN to undergo surgery during that period. Of the 132 cases only one patient died and the percentage of complications was very low, generally lower than analogous series published in the literature. Such complications were progressively reduced in time, leading to a significant reduction in the length of post-operative hospitalization: on the average the 8.8 days were reduced to 5.7 in the last 43 cases. Ipsilateral preoperative hearing, inevitably sacrificed using the ET approach, was already significantly compromised in more than 65% of the cases. On the basis of the present data, it can be asserted that tumor diameter does not in any way preclude the use of the ET approach in AN surgery, rather the reduced morbility and shorter post-operative hospitalization make it the approach of choice for large ANs. PMID- 11771345 TI - [Postural changes in systemic sclerosis: preliminary results]. AB - Systemic Sclerosis (SSc) is a generalized disease of unknown etiology which frequently presents neurological involvement of the central or peripheral nervous system. Besides various types of neuropathies, at times postural alterations of uncertain genesis can be found. Such alternations have never undergone organic study. The present work evaluates the static posture of subjects suffering from SSc without any subjective otoneurological symptoms. A total of 30 subjects-10 normal volunteers and 20 patients suffering from SSc-underwent full clinical examination, immunological testing (immunoglobulin; ANA; anti-ENA, anti centromere, anti-SCL70, anti-DNA, anti-cardiolipin antibodies; C3, C4; circulating immunocomplexes) and capillaroscopy of the periunguis vallecula. The capillaroscopy data showed 2 distinct general pictures of sclerodermic microangiopathy: 1) a "slow pattern", not particularly aggressive, where capillarectasia and neoangiogenesis prevail; 2) an "active pattern", highly aggressive, where architectural disorder, capillary loss with the formation of avascular areas prevail. The 20 SSc subjects following the same therapy and free of any significant otoneurological, vasculo-metabolic or osteoarticular pathologies and the 10 healthy volunteers of compatible age and sex, underwent computerized Static Posturography (S.Ve.P-Amplaid). The immunological examinations showed that all patients were positive for ANA, 12 tested positive for anti-SCL70 antibodies and 7 for anti-centromere antibodies. The results of posturography showed a significant increase in parameter: "surface" and "standard deviation of velocity" with closed eyes. Spectra frequency analysis, processed using a personal method, showed a significant increase in panfrequency oscillations vs. the controls on both axes and both with eyes open and closed. The preliminary results of this study, which from reviewing the literature we believe to be the first of its kind performed, appear to indicate a subclinical suffering upon postural control in SSc: the alterations in the posturographic spectral frequency analysis indicate that all postural control mechanisms are extensively compromised, causing a pluriplanar, multifrequency destabilization both with and without the use of vision. PMID- 11771346 TI - [Ki67 and p53 in laryngeal epithelial lesions: correlations with risk factors]. AB - Laryngeal carcinoma-the prototype of epithelial tumors in the head and neck region-has been the greatest source of information on the biological behavior of such neoplasms. Many Authors have suggested that smoke, and to a lesser extent alcohol, play a role in the genesis of this carcinoma although the exact biological mechanism for such involvement is still not clear. The present study analyzed two important biological indicators (p53 and Ki67) in benign and malignant epithelial lesions of the larynx in an attempt to obtain information on what mechanism correlates the risk factors with the neoplasm. In a group of 172 patients, an in vivo sampling of cells was taken during microlaryngoscopy. These cells were then tested using the immunocytochemical method and the results showed that the neoplastic tissue was significantly more positive to these markers than the pre-cancerous tissues and benign lesions. Moreover, there was also an interesting correlation between the degree of positivity to p53 and exposure to smoke, and to a lesser extent to alcohol, in the oncological patients. Together with other similar results found in the literature, these results hint at a possible explanation for the carcinogenic power of smoke in the larynx and, in general, in the upper respiratory-digestive tract. PMID- 11771347 TI - [Pulsating tinnitus associated with high homolateral jugular bulb and aplasia of the contralateral transverse and sigmoid sinuses]. AB - Pulsating tinnitus is uncommon in the general population. This clinical manifestation can be associated with severe intracranial pathologies and is particularly characterized by a rhythm and synchronism reflecting the heart beat. This work presents a clinical case of pulsating, subjective tinnitus associated with a high homolateral jugular bulb and marked hypoplasia of the contralateral transverse and sigmoid sinuses and the clinical-radiological examinations that made diagnosis possible (particular reference going to CT, MRI and angio-MRI). The intracranial venous drainage pattern varies and is nearly always asymmetrical. The jugular bulb is defined as "high" when its upper edge extends nearly to the level of the tympanic anulus, a condition found in 6-20% of the general population. In many cases it is found by chance as often this condition is asymptomatic. However, the pathological picture associated with pulsating tinnitus is highly complex and requires a detailed diagnostic process which some Authors have arranged in specific "flow charts". Imaging methods are essential and must be identified according to the clinical-audiological findings. The radiologist can avail himself of CT, MRI (in association with angio-MRI), Doppler ultrasound of the supraortic and transcranial branches, and digital imaging subtraction angiography. The therapeutic approach to the patient manifesting a "high" jugular bulb is surgical and makes use of such procedures as: ligature of the internal jugular vein, extracranial transposition of the bulb and, in cases of dehiscence of the limiting bone, hypotympanum repair using an autologous or homologous graft of cartilage or bone. Whichever the case, an accurate cost benefit evaluation must be made, particularly in regard to the risks of endocranial hypertension from the reduced venous drainage, a condition which is significantly increased when concomitant abnormalities of the dural sinuses are present. In the present case, this risk was quite high because of the particular venous morphology described and the patient refused surgery. Currently the patient is under clinical-radiological observation. PMID- 11771348 TI - [Rhinoscleroma with extramaxillary extension: report of a clinical case]. AB - Rhinoscleroma is a chronic, granulomatous infection most frequently affecting the respiratory tract mucosa. The disease is endemic in some geographic areas and is sporadic in Italy, where medio-facial granulomatoses must be differentiated from malignant naso-sinus neoplasms. The present work describes a case of rhino-sinus scleroma with extramaxillary extension, defining the most important clinical characteristics and the treatment performed. PMID- 11771349 TI - [Castleman disease with lateral neck outset. Report of a clinical case]. AB - This work presents the case of a young woman with Castleman's disease, manifest as an isolated, asymptomatic swelling in the supraclavear fossae. A fine needle biopsy was performed on the swelling and cytology on this material proved insignificant (blood cells), while CT and MRI did not show any significant vascular components nor did they provide any elements decisive for diagnosis, the neoformation being similar to a reactive lymph node. To determine the nature of the mass, the lesion was removed by cervicotomy. Histology then led to a definitive diagnosis of a hyaline vascular variant of Castleman's disease. The literature on the topic was then reviewed with an eye to otorhinolaryngological manifestations and the histological aspects and clinical-diagnostic approach are discussed in detail. PMID- 11771350 TI - [Occupational exposure and male fertility. Results of an Italian multicenter study in an exposed population]. AB - It was believed that occupational exposure to several toxic agents could negatively affect male fertility. This paper reports the results of a study on the fertility of couples in whom the man was occupationally exposed to three different toxics: metals, solvents and pesticides, having effects on reproduction. Fertility was evaluated during the time that elapsed between attempting and achieving the first pregnancy of the couple (time to pregnancy- TTP). Exposure to occupational risks during the period preceding conception was defined on the basis of data collected from 153 workers of a mint (exposed to metal and solvents), 322 agricultural workers licensed to handle pesticides and 127 greenhouse workers. Comparing the groups exposed during the conception period with comparable non-exposed groups, we found a slight delay in conception among couples with male exposure to metals (OR = 1.3; 95% CI 0.5-3.6), to solvents (OR = 1.7; 95% CI 0.6-4.6) and to pesticides among greenhouse workers (OR = 1.6; 95% CI 0.8-3.1 for the moderately exposed and OR = 2.4; 95% CI 1.2-5.1 for the heavily exposed). No increase in the risk of conception delay was observed in agricultural workers with generic exposure to pesticides. The results of this study suggest that the workers exposed to metals and solvents and greenhouse workers exposed to pesticides experienced a delay in conception at the time of their wives' first pregnancy. PMID- 11771351 TI - [Evaluation to the exposure to polycyclic aromatic hydrocarbons, benzene, toluene and xylenes in workers in a power plant fueled with heavy oil]. AB - Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has been demonstrated in many industrial sectors. However, up to date there are few studies in the literature on PAH exposure in thermoelectric power plants. The study was aimed at the evaluation of personal exposure to PAHs in workers of a power plant fueled with heavy oil. Exposure to polycyclic aromatic hydrocarbons (PAHs) and to benzene, toluene and xylenes (BTX) was evaluated on power plant workers exposed to heavy fuel oil; the control group consisted of office workers of the same power plant. Altogether 39 subjects were studied, for a total of 84 days of monitoring. Personal environmental exposure, cutaneous exposure and urinary concentrations of 1-hydroxypyrene (1-OHP), trans,trans-muconic acid (TTMA) and nicotine were measured. Personal environmental exposure to PAHs was very low; only maintenance workers showed exposure to total carcinogenic PAHs significantly higher than controls (median levels 3.05 and 0.88 ng/m3 respectively). All workers showed very low levels of dermal exposure to PAHs (less than 1 ng). The median 1-OHP urinary concentrations were 0.16, 0.11 and 0.08 mumol/mol creatinine in the groups of exposed workers and 0.08 mumol/mol creatinine in the control group. Neither the exposed workers nor the controls showed a significant increase in 1-OHP urinary concentrations across the shift. The regression analysis showed a significant effect of cigarette smoking on urinary 1-OHP, while no association was observed between occupational exposure and diet. Personal environmental exposure levels to BTX were very low. TTMA urinary concentrations of the exposed subjects were similar to those of the controls. No significant increase in the TTMA urinary concentrations was observed across the shift and, as expected, smokers showed higher values than non-smokers. The study did not show a measurable intake of PAHs and BTX in power plant workers that could be ascribed to occupational exposure, thus confirming the efficacy of the protective measures in force. PMID- 11771352 TI - [Cause of death among workers of a refinery in Rome]. AB - We evaluated mortality among subjects employed in an oil refinery plant in Rome, Italy. We studied two subgroups of refinery employees: blue collar and white collar workers. A total of 682 men (505 blue collars, 148 white collars, 29 unknown) employed between 1965 and 1992, were followed up for mortality since employment in the plant to July 1999. Standardized Mortality Ratios (SMR), and their 90% Confidence Intervals (90% CI), comparing mortality rates of the cohort members with those of the general population of the Lazio region. For blue collar workers, we performed analyses by latency since first employment and by duration of employment for selected cancer sites. We observed 94 total deaths (100.8 expected) (SMR = 0.93; 90% CI = 0.78-1.11) among blue collar workers and 16 total deaths (31.7 expected) (SMR = 0.50; 90% CI = 0.32-0.77) among white collar workers, and a large deficit of deaths from non-neoplastic cardiovascular diseases (respectively SMR = 0.60; 90% CI = 0.41-0.86 and SMR = 0.18; 90% CI = 0.03-0.56). All cancer mortality was slightly increased only in blue collars (SMR = 1.27 CI = 0.97-1.65). There was an excess risk from cancer of the lung (20 obs SMR = 1.80, 90% CI = 1.19-2.62), bladder (5 obs SMR = 3.19, 90% CI = 1.26-6.72), and benign/unspecified cancer of the brain (4 obs SMR = 4.11, 90% CI = 1.12 10.6). The lower mortality from cardiovascular disease indicates the presence of a strong healthy worker effect. The findings of elevated mortality from cancer of the lung and bladder in blue collar workers are in agreement with those of other studies. Confounding factors from cigarette smoking might have played only a marginal role in influencing the results. Exposure to polynuclear aromatic hydrocarbons (PAHs) is a plausible explanation for the excesses found. PMID- 11771353 TI - [Evaluation of the occupational exposure risk to non-ionizing radiation in the working environment in a metal mechanical industry]. AB - Among the various sources of risk present in a metal engineering industry, it is important to take into account the risk related to non ionizing radiations. New technologies, in fact, use radiations in different equipment to an ever increasing extent. It is therefore important, on the basis of the current regulations, to carry out a census, since the frequencies used in the workplaces vary widely. It is also important to measure exposure, in order to limit access areas, but, above all, to measure personal doses, since it is useful to record the personal doses in view of the uncertain regulation and in connection with exposure levels lower than the reference in order to limit non-stochastic effects, as was shown in our study. Information and training of personnel, health surveillance and the specific observation of critical groups of workers, are also of fundamental importance. PMID- 11771354 TI - [Job fitness definitions in workers exposed to biological risks in a health care environment: highlights of a case report]. AB - The definition of the specific job fitness for individual clinical cases often requires significant detailed investigation by the occupational physician. Such professional commitment is particularly important when biological risks in health care personnel are concerned. In fact, besides correct diagnostic procedures and the specific risk assessment implications, the level of competence of the worker, the safety of patients, work organization, risk perception and health education are also especially relevant. The aim of this paper is to report the case of a young nurse employed in the haematology section of the division of internal medicine, who was in charge of preparing and administering antineoplastic drugs. Risk assessment and a thorough clinical evaluation were performed in order to make a job fitness decision, with specific reference to biological risks. The nurse was suffering from membranous glomerulonephritis and was therefore being treated with various immunosuppressant agents. When she came to occupational physician, risk assessment showed that the preparation and administration of the antineoplastic drugs was not safely performed; the clinical picture showed moderate leukopenia while the kidney disease was functionally controlled. The worker was judged unfit to manipulate antineoplastic or perform activities in divisions at high biological risk. Recommendations were given to follow standard precautions and to follow up the case after cessation of immunosuppressant therapy. The case dealt with a specific biological risk assessment in health care settings and with the need to obtain through knowledge of the clinical state of the subject. Such information is necessary to assess job fitness, also giving recommendations related to employer's and employee's responsibility. The case report also provided the opportunity of underlining the role of the occupational physician in the management of cases of particular clinical relevance and of stressing the necessity of continuing scientific updating in order to reach sound conclusions. PMID- 11771355 TI - [Occupational diseases have decreased, they almost do not exist anymore]. PMID- 11771356 TI - [Estimating the number of exposures to asbestos at work in Italy: the inconsistency of the existing evaluations]. PMID- 11771357 TI - [Health surveillance of workers formerly exposed to asbestos]. PMID- 11771358 TI - [Bilateral vestibular syndrome. Diagnostic criteria]. PMID- 11771360 TI - [Evaluation of the treatment of benign paroxysmal positional vertigo with the DHI S questionnaire]. AB - Benign paroxysmal positional vertigo (BPPV) is a recurrent chronic disease and its handicap is usually underestimated. The aim of this study is to determine the impact of the treatment by Epley maneuver on short-term BPPV-related quality of life. Forty-two individuals with BPPV were included: 39 with posterior canal affected, 2 with the lateral canal and one with the anterior canal. Diagnosis was established if a consistent clinical history was found and Dix-Hallpike test (DHT) in cases with canal posterior involvement. Subjects with positive DHT were treated by a single Epley maneuver and were recommended to avoid supine for the next 48 hours. The BPPV relapses were investigated at 7th and 30th day post treatment. BPPV-associated quality of life was evaluated by the Dizzness Handicap Inventory Short-form (DHI-S) at days 1st and 30th post-treatment. Total and partial scores for emotional, physical and functional subscales were compared by Wilcoxon test for paired samples. Dix-Hallpike test was found positive in el 59% individuals (23/39), and 41% cases did not required any treatment. Among 23 patients treated with Epley maneuver, DHT was found negative in 90% at 30th day follow-up. Mean and standard deviation of the total scores obtained in the DHI-S at the first day were 19.22 +/- 9.66 in the DHT positive-patients and 19.79 +/- 10.14 in the whole group (DHT positive or negative). These scores significantly decreased to 10.84 +/- 10.99 at 30 days post-treatment (p = 0.002 and p = 0.001, respectively). In conclusion, the DHI-S is a specific health questionnaire able to assess BPPV-related health and the effectiveness of treatment. PMID- 11771359 TI - [Magnetic resonance: first choice test in the screening of internal auditory canal and cerebellopontine angle tumors]. AB - Although internal auditory canal (IAC) and cerebellopontine angle (CPA) tumors are rare, their clinical suspicion is quite common in the otolaryngology office. MRI is the imaging modality of choice in diagnosing these tumors. Perceived high costs may prevent clinicians from using it as a screening tool. A protocol designed to improve cost-effectiveness in such diagnosis results in a more rationale clinical practice. Our aim was to evaluate the usefulness of MRI as screening tool in diagnosis of IAC and CPA tumors in our population. Between March 1998 and March 2000, a prospective series of 200 cases had a MRI screening requested. MRI were performed following Fast Spin Echo technique, providing T2 weighted images. Gadolinium enhanced MRI was reserved for selected cases. We report on 190 MRI done. We found 7 neuromas (3.5%), one CPA metastasis, one epidermoid cyst and 9 IAC vascular anomalies. Only 138 cases (69%) had normal MRI images. When used following a designed protocol, MRI is our procedure of choice while screening IAC and CPA tumors because it is a cost-effective tool. PMID- 11771361 TI - [Implantation of a program for the early detection of neonatal hearing loss]. AB - Permanent childhood hearing impairment is a serious public health problem. Identification by screening in the first few months of life has the potential to improve affected children development. Neonatal hearing screening programs endorse the WHO requirement for a cost efficient screening. This paper shows the implementation of a medium-size hospital-based universal newborn hearing screening program using transient evoked otoacoustic emissions. Operational procedures and requirements are discussed. Quality control and results are showed. PMID- 11771362 TI - [Determination of PTH I in hyperparathyroidism surgery. Our experience]. AB - Our Service of Otolaryngology has performed 90 parathyroidectomies at all since april 1990 to 2000 on 92 patients sent to us with diagnosis of hyperparathyroidism. 67 patients were diagnosed as primary hyperparathyroidism; 22 as secondary and 3 cases corresponded to tertiary hyperparathyroidism. We analysed a string of variables before and after the surgery standing out the recent estimate of rapid PTH i levels. The kind of surgery we performed was the removal of adenoma in 63 cases; 23 patients were put to subtotal parathyroidectomy and 4 to a total one. An exploratory neck surgery was performed in two patients without finding a parathyroid pathology. We compare the obtained results with other published series and we think it can be useful to determinate the rapid paratohormone levels (PTH i) pre and postsurgery (only used in 3 cases by now) in order to predict the clinic response of the patients with hyperparathyroidism. PMID- 11771363 TI - [Recurrent Bell's facial palsy: our experience]. AB - Recurrent facial palsy is noted infrequently in the literature. We present a comparative study of recurrent Bell's palsy (RBP) with regard to non-recurrent Bell's palsy (NRBP). Afterwards we compare among RBP cases those of ipsilateral recurrence (RRBP) to those of contralateral one (ARBP). We constate that non recurrent Bell'palsy formes behave similarly to the contralateral recurrent forms. PMID- 11771364 TI - [Analysis of the relationship between chronic pharyngitis and tonsillectomy with the microbiologic study of the cavum]. AB - Chronic pharyngitis is an usual process with difficult treatment. It has been related to tonsillectomy. This study collected 224 patients suffering from chronic pharyngitis, 55 tonsillectomies and 169 without operation. Bacteriological culture was done from nasopharynx in the different seasons. Microorganisms more frequent were Staphylococcus aureus, Corynebacterium sp and Aspergillus. The time between the tonsillectomy and this study has been of more than 17 years. No relationship has been found between chronic pharyngitis and tonsillectomy, considering types of microorganisms, seasons, numbers of microorganisms isolated per culture, Gram stain, and age of the patients. PMID- 11771365 TI - [Sinonasal hemangiopericytoma]. AB - The hemangiopericytoma is an infrequent vascular tumour in the nose, that produces epistaxis and obstructive respiratory clinical like principal symptoms. It has, in the nose, special clinical characteristics that makes it different of the others localitations. We report a case of nasosinusal hemangiopericytoma with appearance of polyposis and treated with nasosinusal endoscopic surgery; after that, the patient had a complete remission and subsequent follow-up without recurrence. We review the literature and study the most important characteristics. PMID- 11771366 TI - [Asymptomatic acoustic neurinoma associated with hypophyseal macroadenoma]. AB - The widespread use of gadolinium-enhanced MRI (Gd-MRI) in our hospitals has supposed an increase in detection of asymptomatic acoustic neuromas (AN) as incidental finding. Concurrent primary intracranial tumors of different cell types are extremely uncommon. CLINICAL CASE: A 23 year-old woman complained of irregular menstrual cycles and galactorrhea for two years. A Gd-MRI scan showed a pituitary macroadenoma and an AN of 1.4 cm. with intracanalicular and cisternal extension. The patient did not have any otologic or neuro-otologic symptoms or signs. Audiograms revealed bilateral normal hearing. The results of acoustic reflex test and electronystagmographic caloric tests were normal. The AN underwent radiosurgery treatment. DISCUSSION: The literature about atypical AN is reviewed, giving a particular concern on asymptomatic cases. We only have found one case of association between AN and pituitary adenoma. The real prevalence of AN in general population is discussed. PMID- 11771367 TI - [Cutaneous leishmaniasis: report of a case]. AB - We present one cutaneous leishmania case that begun with cervical adenopathy without evident focus. We revise its diagnosis and treatment. PMID- 11771368 TI - [Solitary plasmacytoma of the head and neck. Report of 3 cases and review of the literature]. AB - Solitary plasmocytoma is a rare plasmactic cell tumor occurring in the head and neck. These constitute, less than 1% of all head and neck malignancies. On initial presentation they must be differentiated from multiple myeloma. This may prove to be difficult because a varying percentage may be associated at a later date with the development of multiple myeloma. We describe three cases of plasmocytomas, one occurred in the larynx, in the cavity nasal and other in the skull base. The clinical characteristics, diagnosis criteria and therapeutic problems (radiation, surgery or a combination of booth) are discussed and reviewed in the literature. PMID- 11771369 TI - [Parapharyngeal abscess secondary to peritonsillar abscess in childhood]. AB - We report a case of parapharyngeal abscess in a five-years-old girl, secondary to a local extension of a peritonsillar abscess. The typical signs of peritonsillar abscess, medially displaced tonsil and displacement of the uvula toward the opposite side, were either less pronounced than usual. In this case, with parapharyngeal involvement, the treatment was abscess tonsillectomy under intravenous anti-. PMID- 11771370 TI - Case of the month. Suspicion--an important EMS asset. PMID- 11771371 TI - Patient simulators. Changing the face of EMS education. PMID- 11771372 TI - Plastination. An innovative approach to preserving anatomical specimens & teaching anatomy to EMS personnel. PMID- 11771373 TI - Teamwork. University of Miami uses competition to sharpen EMS team performance. AB - Many argue that experience is the best teacher. However, it's often dangerous for the patient and impractical for an EMS system to assess prehospital providers in their actual working environment. Simulated scenario competition fosters clearer thinking and translates into more effective action and enhanced patient outcomes during true emergencies. PMID- 11771374 TI - GO-4 ALS. Mini ALS units take Honolulu EMS by storm. PMID- 11771375 TI - Systemic toxins. Signs, symptoms & management of patients in septic shock. PMID- 11771376 TI - Role of G protein beta gamma complex in receptor-G protein interaction. PMID- 11771377 TI - Phosducin down-regulation of G-protein coupling: reconstitution of phosducin and transducin of cGMP cascade in bovine rod photoreceptor cells. PMID- 11771378 TI - Analysis of signal transfer from receptor to Go/Gi in different membrane environments and receptor-independent activators of brain G protein. PMID- 11771379 TI - Elucidating kinetic and thermodynamic constants for interaction of G protein subunits and receptors by surface plasmon resonance spectroscopy. PMID- 11771380 TI - Identification of modulators of mammalian G-protein signaling by functional screens in the yeast Saccharomyces cerevisiae. PMID- 11771381 TI - Expression of alpha subunit of Gs in Escherichia coli. PMID- 11771382 TI - Purification of G protein isoforms GOA and GOC from bovine brain. PMID- 11771383 TI - Coexpression of proteins with methionine aminopeptidase and/or N myristoyltransferase in Escherichia coli to increase acylation and homogeneity of protein preparations. AB - New plasmid constructs described in this article allow the coexpression in bacteria of any protein with several different NMT proteins, including the recently cloned full-length human NMT1 and 2, and with increased expression of bacterial Met-AP. Through the use of these plasmids in different combinations it should be possible to improve the homogeneity of a large number of recombinant protein preparations by the complete removal of the initiating methionine and increased extent of N-myristoylation. The new reagents described in this article are available upon request. PMID- 11771384 TI - Purification of G protein beta gamma from bovine brain. PMID- 11771385 TI - Separation and analysis of G protein gamma subunits. PMID- 11771386 TI - Activity of G gamma prenylcysteine carboxyl methyltransferase. PMID- 11771387 TI - Preparation and application of G protein gamma subunit-derived peptides incorporating a photoactive isoprenoid. PMID- 11771388 TI - Expression and functional analysis of G protein alpha subunits in S49 lymphoma cells. PMID- 11771389 TI - Mouse gene knockout and knockin strategies in application to alpha subunits of Gi/Go family of G proteins. PMID- 11771390 TI - Determining cellular role of G alpha 12. AB - Using the expression strategies described here, we have demonstrated a model system whereby the sequential signaling events involved in cell proliferation and subsequent transformation regulated by G alpha 12 can be investigated. The model system presented here can also be used to study the temporal interrelationships between small GTPases, kinases, and other signaling proteins involved in G alpha 12-signaling pathways. Further analyses using this model system and the strategies presented here should provide valuable clues in defining the signaling network regulated by G alpha 12 in stimulating cell proliferation and oncogenic transformation. PMID- 11771391 TI - Analysis of G protein activation in Sf9 and mammalian cells by agonist-promoted [35S]GTP gamma S binding. PMID- 11771392 TI - Targeted, regulatable expression of activated heterotrimeric G protein alpha subunits in transgenic mice. PMID- 11771393 TI - Inducible, tissue-specific suppression of heterotrimeric G protein alpha subunits in vivo. PMID- 11771394 TI - Construction of replication defective adenovirus that expresses mutant G alpha s Q227L. PMID- 11771395 TI - Expression of adenovirus-directed expression of activated G alpha s in rat hippocampal slices. PMID- 11771396 TI - Quench-flow kinetic measurement of individual reactions of G-protein-catalyzed GTPase cycle. PMID- 11771397 TI - Analysis of genomic imprinting of Gs alpha gene. PMID- 11771398 TI - Subcellular localization of G protein subunits. PMID- 11771399 TI - Fluorescence approaches to study G protein mechanisms. PMID- 11771400 TI - Neuroanatomical localization of receptor-activated G proteins in brain. PMID- 11771401 TI - Defining G protein beta gamma specificity for effector recognition. PMID- 11771402 TI - Ribozyme-mediated suppression of G protein gamma subunits. AB - Efforts to determine the sequence of the human genome have resulted in sequence information on thousand of genes. Now, the challenge is to determine the functions of this myriad of genes, including those encoding the G protein subunit families. In this chapter, we describe the successful use of ribozymes to inactivate mRNAs expressed from the G protein gamma subunit genes. Ribozymes are unique in that they can inactivate specific gene expression, and thereby can be used to help identify the function of a protein or the role of a gene in a functional cascade. Compared to other means of identifying the role of a gene (i.e., transgenic or knockout animals), ribozymes are specific and relatively easy to use. Moreover, ribozymes are able to discriminate closely related, or even mutated, sequences within gene families. Thus, in addition to elucidating functions, ribozymes have the potential to be used in treating genetic disorders associated with mutations of G protein subunits. PMID- 11771403 TI - Use of scanning mutagenesis to delineate structure-function relationships in G protein alpha subunits. PMID- 11771404 TI - Development of Gs-selective inhibitory compounds. PMID- 11771405 TI - Characterization of deamidated G protein subunits. PMID- 11771406 TI - Determining G protein heterotrimer formation. PMID- 11771407 TI - Use of peptide probes to determine function of interaction sites in G protein interactions with effectors. PMID- 11771409 TI - Evolutionary traces of functional surfaces along G protein signaling pathway. PMID- 11771410 TI - Discovery of ligands for beta gamma subunits from phage-displayed peptide libraries. AB - We have described a method using polyvalent peptide display on filamentous phage that can be used to identify ligands that bind to G protein beta gamma subunits. Also described is how to construct phage that have known beta gamma binding sequences fused to the coat protein to allow a competition analysis to be performed. Once selected or constructed, these phage-bearing beta gamma-binding peptides are powerful tools for mapping interaction sites for beta gamma binding proteins and can be used to begin to dissect the unique modes of binding for individual beta gamma subunit-regulated effectors. PMID- 11771408 TI - Protein interaction assays with G proteins. PMID- 11771411 TI - Exploring protein-protein interactions by peptide docking protocols. PMID- 11771412 TI - Design and use of C-terminal minigene vectors for studying role of heterotrimeric G proteins. PMID- 11771413 TI - Structural characterization of intact G protein gamma subunits by mass spectrometry. PMID- 11771414 TI - Quantitative assays for GTPase-activating proteins. PMID- 11771415 TI - Analysis of RGS proteins in Saccharomyces cerevisiae. PMID- 11771416 TI - Purification of RGS protein, Sst2, from Saccharomyces cerevisiae and Escherichia coli. PMID- 11771417 TI - RGS domain: production and uses of recombinant protein. PMID- 11771418 TI - Screening for interacting partners for G alpha i3 and RGS-GAIP using the two hybrid system. PMID- 11771419 TI - Assay of RGS protein activity in vitro using purified components. AB - Single-turnover and steady-state GTPase assays are an effective means to identify and characterize interactions between RGS and G alpha proteins in vitro. The advantage of the single turnover GTPase assay is that it permits simple and rapid assessment of RGS protein activity toward a putative G alpha-GTP substrate. Moreover, once an interaction between an RGS protein and a G alpha-GTP subunit has been identified, the single-turnover assay can be used to determine Michaelis Menten constants and/or KI values for other competing G alpha substrates. A disadvantage of the single-turnover assay is that a negative result does not preclude the possibility of an interaction between given RGS and G alpha proteins in vivo. Inappropriate reaction conditions or the presence (or absence) of appropriate posttranslational modifications may result in small or undetectable increases in RGS protein-dependent GTPase activity. In these cases it may be tempting to examine RGS protein activity using steady-state GTPase assays in phospholipid vesicles reconstituted with receptors and heterotrimetric G proteins. The advantage to monitoring steady-state GTPase activity in reconstituted proteoliposomes is that ligand-dependent activation of the receptor facilitates GDP dissociation, such that effects of RGS proteins can be observed; multiple cycles of GTP binding and hydrolysis then amplify the GTPase signal. Additionally, the presence of the phospholipid membrane can increase the local RGS protein concentration approximately 10(4)-fold, permitting observation of interactions that are weak in solution. The primary disadvantage of the reconstituted system is the requirement for receptor purification, a technically demanding undertaking in comparison to the purification of G alpha, G beta gamma, and most RGS proteins. PMID- 11771420 TI - Measuring RGS protein interactions with Gq alpha. PMID- 11771421 TI - Dissecting receptor-G protein specificity using G alpha chimeras. AB - In conclusion, by taking advantage of the overall sequence homology and structural similarity of G alpha subunits, functional chimeric G alpha subunits can be generated and used as tools for the identification of sequence-specific factors that mediate receptor: G protein specificity. The [35S]GTP gamma S binding assay and the affinity shift activity assay are two sensitive biochemical approaches that can be used to assess receptor: G protein coupling in vitro. These in vitro assays limit confounding influences from cellular proteins and allow for the strict control of receptor: G protein ratios. PMID- 11771422 TI - Assays of complex formation between RGS protein G gamma subunit-like domains and G beta subunits. PMID- 11771423 TI - RGS function in visual signal transduction. PMID- 11771424 TI - Molecular cloning of regulators of G-protein signaling family members and characterization of binding specificity of RGS12 PDZ domain. PMID- 11771425 TI - Use of dominant negative mutations in analysis of G protein function in Saccharomyces cerevisiae. PMID- 11771426 TI - Functional assays for mammalian G-protein-coupled receptors in yeast. PMID- 11771427 TI - [Attention deficit and hyperactivity in the child]. AB - Attention deficit and hyperactivity disorder associates three specific symptoms: an attention deficit disorder, hyperactivity, and impulsiveness. Most often, this trouble induces educational difficulties with learning disabilities, family difficulties due to parents intolerance and a negative esteem of oneself originating from a depressive personal experience. The differential diagnosis essentially lays in mood troubles, anxiety troubles and psychotic troubles which necessitate a careful biography. The specialized neuropsychological explorations show perturbations at the level of the attentionnel processes and cognitive strategies of the child. The etiopathogeny of the trouble is at the heart of present researches which show a cerebral dysfunction affecting the frontostriatal structures more accentuated on the right. However, the majority of researchers are in favour of a multifactorial etiology: neuropsychological, neurochemical, neurophysiological and genetic. The treatment is based on a psychopedagogical intervention and the prescription of psychostimulants. The evolution is generally suitable to adolescence. PMID- 11771428 TI - [Quality control in tumor marker values: methology, results and potential problems]. AB - Ensuring the quality is one of the first preoccupations of every biologist. However, measuring the circulating tumor markers could be more vital especially that the result is decisive for the diagnostic and the therapeutic attitude. In this study, we report methods used for an internal and external < or = quality control < or = program applied in the immunology laboratory of Sfax university hospital for the dosage of tumor markers AFP, CEA and CA15-3. The results obtained are analysed comparatively with those reported in literature. Factors causing discrepancies in the results of tumor marker measurements are recalled. PMID- 11771429 TI - [The etiology of hypercalcemia: a study of 47 cases in a hospital internal medicine service]. AB - In this study, we are presented the clinical and the aetiologic features of 47 patients having hypercalcemia (total serum calcium > or = 2.7 mmol/l). Our results show a positive significantly correlation between the degree of the hypercalcemia and the severity of the clinical symptomatology. As for to the aetiology, the multiple myeloma, the hyperparathyroid and the neoplastic process constituted 78% of the total aetiology. PMID- 11771430 TI - [Intestinal metaplasia at the gastroesophageal junction - epidemiologic and histologic aspects. Report of 164 cases]. AB - Adenocarcinoma of the gastric cardia is increasing in incidence. The purpose of this study was to determine whether intestinal metaplasia of the esophagogastric and having a malignant potential junction can be considered as an ultra-short segment Barrett's esophagus. To study the epidemiologic and histological features of the intestinal metaplasia of esophagogastric junction two groups of patients were compared for the prevalence of this condition. Group 1 included 82 patients with gastroesophageal reflux symptoms et group 2 consisted of 82 healthy individuals. Both groups had two biopsy specimens taken from the esophagogastric junction. Histological evidence of intestinal metaplasia was defined as specialized columnar epithelium containing goblet cells staining with alcian blue at pH 2.5. Intestinal metaplasia of the esophagogastric junction was present in 12 patients in group 1 and 9 individuals in group 2. The global prevalence of this condition was 12.8% and there was not a statistically significant difference in the prevalence of this condition between the two groups. A significant difference could not be found when sex was considered. There was a significant association between this condition and older age (p = 0.01). Intestinal metaplasia of the esophagogastric junction and Barrett's esophagus do not have the same epidemiologic features. Therefore, we suggest that screening biopsy specimens of the esophagogastric junction be limited to study protocols at this time. PMID- 11771431 TI - [Clinical aspects and etiology of lower respiratory tract infections in hospitalized children]. AB - The authors report a prospective study conducted in one of the general pediatrics unit. One hundred one children, aged 20 days to 12 years, admitted with acute lower respiratory tract infections have been studied on clinical paraclinicals and etiology grounds. All children had a chest Ray roentgenogram, a total blood cell count and C-reactive protein. The detection of a viral agent in nasopharyngeal aspirate by immunofluorescent technic were performed. 85% of patients have bronchiolitis, the chest--Rays showed an abnormal pictures in 84.2% of cases, an anaemia was present in 54.7%. Viral agent as identified in 58 patients, the RSV indicated in 56 cases. Bacterial infection as present in 57 of the 101 children. A mixed viral-bacterial infection as documented in 28 cases. Among bacterial causes the predominant agent as Haemophilus influenzae 24, Branhamella Catarrhalis 17, streptococcus pneumoniae in 16 cases. Early empiric antibiotic as performed. All patients recovered uneventfully. PMID- 11771432 TI - [Internal abdominal hernias. Report of 8 cases]. AB - Internal abdominal hernias are rare. There unexpected discovery at laparotomy confront the surgeon at anatomic diagnosis problem. 8 cases of internal abdominal hernias were observed between 1989 and 1998: transmesenteric in 3 cases, mesosigmoidal in 2 cases, paraduodenal in 2 cases, needing intestinal resection. Hernia foramen were sutured in all of cases without hernial sac's resection. The results of the present series were excellent without recurrence. Literature review show that internal hernias were responsible of complex anatomic and surgical presentations. The primary task of the surgeon is not so much to establish the diagnosis of internal hernia but intestinal occlusion to decide at time urgent operation. PMID- 11771433 TI - [Serum copper levels in obesity: a study of 32 cases]. AB - Abnormalities of copper distribution in tissues and serum has been described in obese subjects. In this prospective study, we evaluated the seric level of copper by atomic absorption in a group of 32 obese (BMI > or = 30 kg/m2) compared to a group of 32 healthy subjects. We have noted an elevation of serum copper in obese with a middle level of 133 mg/dl significantly superior to the middle level of serum copper of healthy subjects, 108 mg/dl (p < 0.001). In another hand, we have noticed that the levels of serum cooper rise with the BMI. In fact, 58.3% of the obese that have a BMI > or = 40 kg/m2 show a high concentration of serum copper although only 5% of obese with BMI < 40 kg/m2 show this high concentration. This work must be completed by the determination of ceruloplasmin levels in a larger group of obese in order to establish correlations between the serum ceruloplasmin levels, the serum copper levels and the obesity. PMID- 11771434 TI - [Comparative study of the efficacy and tolerance of 12% glycolic acid cream and 0.05% retinoic acid cream for polymorphic acne]. AB - Topical retinoic acid has demonstrated its efficacy in acne. Glycolic acid has also keratolytic action and could be interesting to treat acne. OBJECTIVE: To evaluate the efficacy and safety of topical glycolic acid (Glyco A 12%) and retinoin acid (Kefrane 0.05%) on facial acne lesions. METHOD: It was a randomised double blind study of 40 patients, divided in 2 groups, 20 receiving GlycoA cream (Group A) and 20 receiving Kefrane cream (group B). Medical exam was realised by the same physician at day 0, 21 and 45. The improvement of acne as well as side effects were assessed by both the physician and the patients themselves. RESULTS: 2 patients developed severe eczema of the face and were excluded (one from group A and one from group B). 22 patients followed totally the study. 90% of group A and 83.3% of group B patients improved significantly their lesions. A comparative tolerability was observed for both groups. CONCLUSION: Glyco A cream could be a good treatment for acne even in dark skin patients. PMID- 11771435 TI - [Solitary pleural fibroma: report of two cases and review of the literature]. AB - The pleural fibroma is an uncommon tumor of pleura. Its Diagnosis is guided by chest imaging and confirmed by surgery and histological exam. We respectively report two observations of solitary pleural fibroma in 68 and 27 old years patients. The authors expose the circumstances of discovery and present clinical features, diagnosis explorations and therapeutical methods. Prognosis depends primary on histological findings and malignant recurrences are possible. PMID- 11771436 TI - [Pure primitive dysautonomia or Bradbury-Eggleston syndrome. Report of 3 cases]. AB - The primary autonomic failure (Bradbury-Eggleston syndrome) is rare. We report three cases (two females and one male) who are 55 year old with orthostatic hypotension, tachycardia, and other signs of dysautonomia. They hadn't a pyramidal, extrapyramidal or cerebellar syndromes. The other causes of postural hypotension are excluded. The autonomic dysfunction was confirmed by autonomic reflex tests and by evaluating of cardiac reflex function; these included heart rate responses to deep breathing and to the valsalva maneuver. Hypotension occurs in a variety of clinical setting; ascertainment of the cause is by non means easy. Primary autonomic failure remains a diagnostic category based on exclusion; its pathophysiology isn't well know and its treatment is only symptomatic. PMID- 11771437 TI - [Arrhythmogenic right ventricular dysplasia. Report of 4 cases]. AB - Arythmogenic right ventricular dysplasia (ARVD) was supposed to be a part of VHL diseases; ARVD is in fact a well defined anatomo-pathological entity, originally described by Fontaine and Frank in 1977. The authors report 4 new cases of ARVD were desmitted at the department of cardio A. The disease was announced by the usual rhythmic disorders. The diagnostics of ARVD was based upon a bundle of electrical, echocardiographic and histological arguments. The rhythmic stability was obtained in three cases with medical treatment, the endocavity ablation was necessary in one case. A study of the diagnostic and therapeutic forms is performed from a literature review. PMID- 11771438 TI - [Tracheal atresia. A case report]. AB - The tracheal agenesis is a rare malformation of the respiratory tract. It must be suspected in any new born with respiratory distress, absence of crying, and difficulty or impossibility of intubation. Since the initial case report by Payne in 1900, 87 cases have been reported in the literature. The authors report one case of tracheal agenesis out of 2500 autopsy realised in the laboratory. PMID- 11771439 TI - [Leukocytoclastic vasculitis, cryoglobulinemia and medullary aplasia associated with hepatitis C]. AB - Various clinical and immunological extrahepatic manifestations were described during infection by hepatitis C virus (HCV). We reported a rare association, within the same patient, made up with a cutaneous leucytoclastic vasculitis, cryoglobulinemia and aplastic anemia. A 70 years old woman with infection by HCV diagnosed four years ago, was hospitalized due to upper members purpura and six cutaneous ulcerations. Complete blood count revealed a pancytopenia. Prothrombin time was at 65%, AST, ALT an d GT were within normal limits. Test for antibodies to HCV en serum was positive. Bone marrow aspiration showed marked hypocellularity. A skin biopsy showed leucocytoclastic vasculitis of small vessels. Interferon a therapy was not indicated because aplastic anemia. Simultaneous occurrence of cutaneous vasculitis, cryoglobulinemia and aplastic anemia during HCV infection lays the question of their mechanism. Purpura and cutaneous ulcerations can be due to cryoglobulinia. PMID- 11771440 TI - Efficacy of neo- and adjuvant treatment modalities in gastrointestinal cancer patients. AB - Data which have emerged from randomized clinical trials are inconclusive regarding the efficacy of neoadjuvant chemoradiation therapy for patients with esophageal cancer. In 2001, available data appear to support the use of adjuvant chemoradiation therapy following the complete resection of a gastric cancer, adjuvant chemotherapy following the resection of a stage III (and--probably- "high-risk" stage II) colon cancer, and the use of adjuvant (and most likely neoadjuvant) chemoradiation therapy for stages II and III rectal cancer. PMID- 11771441 TI - [Molecular markers in colorectal carcinoma]. AB - Due to introduction of immunohistochemical, cytochemical, molecular and cytogenetic methods in oncologic research, understanding of genetic basis in tumor genesis is improving. Furthermore, different studies gave evidence for prognostic relevance of some (cyto)genetic alterations or residual tumor cells in lymph nodes or bone marrow, respectively. More prospective, large studies are needed, before applying these findings in clinical routine, and the methods have to be standardized. PMID- 11771442 TI - Laparoscopic colectomy for colon cancer--a trial update. AB - OBJECTIVES: A prospective randomized trial was designed to test the hypothesis that disease-free survival and overall survival are equivalent regardless of whether patients receive laparoscopic assisted colectomy (LAC) or open colectomy. Secondary and tertiary aims will test the safety of LAC and the impact of LAC on quality of life and costs, respectively. METHODS: 1200 patients will be accrued and randomly assigned to LAC or open colectomy. Consenting adults with primary colon cancer without previous or concurrent malignancies and with tumors considered resectable for cure are eligible for enrollment. Patients will be followed postoperatively for evidence of recurrence and for survival and perioperatively for morbidity, mortality, quality of life, and cost end points. RESULTS: Over 800 patients have been enrolled to date. Early trial results are available for 408 patients, 203 open and 205 LAC. As anticipated, patients are evenly distributed within the two treatment arms according to age, gender, and anesthesia risk (ASA classification). In the open arm, the mean age is 69 with 52 percent females, 87 percent ASA I/II and 13 percent ASA III. In the laparoscopic arm, the mean age is 67, with 48 percent females, 87 percent ASA I/II, and 13 percent ASA III. A total of 160 right and 117 sigmoid colectomies have been performed. Extent of resection data is also available and all parameters tested show no difference between the LAC and open cases: for the laparoscopic vs open colectomy, total bowel length 26 cm vs 27 cm; proximal margins 12 cm vs 11 cm; distal margins 10 cm vs 12 cm; mesenteric length 9 cm vs 8 cm. Similarly, the number of nodes resected for laparoscopic colectomy is essentially the same (mean 12 lymph nodes) to that for open surgery (mean 13 nodes). CONCLUSIONS: Although this study is ongoing; preliminary results suggest that open and LAC provide for the same extent of resection. The quality of life portion of the study is now complete and data will soon be available. PMID- 11771443 TI - Lymphatic mapping and sentinel node identification for colorectal cancer. AB - The primary treatment of resectable CRC is surgical resection. Postoperative adjuvant therapies are recommended when lymph node metastases are found (stage III). There is evidence that about 20% of node negative CRC cases (stage II) are understaged, i.e., they are actually node positive (stage III). New intraoperative procedures (lymphatic mapping and sentinel node identification) that are able to detect occult macro- and micrometastases. Molecular assessment of nodal disease should improve the current staging criteria for colon cancer and could influence recommendation for adjuvant treatment. PMID- 11771444 TI - Surgery, radio- and chemotherapy for multimodal treatment of rectal cancer. AB - The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors. PMID- 11771445 TI - Transanal excision for T1 and T2 rectal cancer--efficacy of local resection vs. adjuvant therapy. Extended abstract. AB - The principal goal in the management of any patient with rectal cancer is to provide the optimum chance for cure while maintaining their quality of life. Treatment options over the past century have reflected our ability to provide safe surgical care and, more recently, a greater understanding of tumor biology. Prior to the introduction of the abdominoperineal resection (APR) that was reported in the Lancet in 1908 by Sir Ernest Miles, perineal excision was the accepted approach for nearly all rectal cancer. Unfortunately, inconsistent surgical outcomes and high local recurrence even in Miles personal experience promoted alternative treatment. The acceptance of APR and subsequently low anterior resection reduced recurrence and improved long-term survival but often with the cost of decreased quality of life. A recent review by McCall et al. report disease specific recurrence at 8.5 percent, 16.3 percent and 28.6 percent for cancer stages I, II and III respectively with an overall reported recurrence rates following APR ranging from 10 to 29 percent. Reported five-year survival rates range 78 to 100 percent for stage I, 45 to 73 percent for stage II and 22 to 66 percent for stage III. The wide variations in recurrence and survival rates likely reflect differences in tumor size, proximity to the anal canal, depth of penetration in the rectal wall and unfavorable histologic characteristics. An additional confounding variable in the management of rectal cancer has been the use of adjuvant therapy do in part to the timing and dose/fractionation differences utilized. Given the variation in outcomes with APR and ongoing concerns regarding morbidity and quality of life issues associated with radical resection, many centers have revisited local therapy as a means of managing select patients with distal rectal cancers. These therapies include transanal and transcoccygeal excision as well as endocavitary radiation and even fulguration. It is the belief of many surgeons that our ability to more accurately stage patients preoperatively and add adjuvant therapy when indicated will improve our success with local excision. PMID- 11771446 TI - Prophylactic surgery in families with familial adenomatous polyposis (FAP) and in colitis. AB - Colorectal cancer is the second most common cause of death from malignant tumors in western countries with approximately 3800 new cases/year in Switzerland. For individuals known to be at high risk for the development of colorectal cancer, screening, chemoprevention and/or prophylactic surgery are the only tools to avoid unnecessary premature death from this disease. With modern molecular and/or genetic testing the risk of developing colorectal cancer can be more precisely estimated on an individualized basis. These individuals need to be enrolled in strong surveillance programs and are clear candidates for prophylactic surgery. The risk of prophylactic surgery (morbidity, mortality, quality of life following surgery) must be clearly weighted against the increasing risk of cancer. These patients should be treated in experienced centers for colorectal surgery in close connection with a genetic testing and counseling team, a molecular laboratory and a psychological support group. PMID- 11771447 TI - [The anti-atherogenic mechanism of action of physical training in patients with coronary heart disease]. AB - In randomized trials, moderate to aggressive lipid-lowering therapy as well as regular physical exercise have both been shown to restore endothelial function, slow progression and in some patients even lead to regression of coronary artery disease. Furthermore, a reduced rate of cardiac events, morbidity and mortality have been documented. Similarly, regular physical exercise training has been identified to contribute independently to beneficial changes in the risk factor profile, retardation of the progression of coronary lesions and has been associated with a reduced rate of mortality. Therefore, besides adhering to a low fat diet, patients with coronary artery disease should further be motivated to include physical exercise in their daily routine. Although it has been puzzling how exercise training exerts antiatherogenic effects, accumulating evidence has recently unraveled some of the underlying cellular and molecular pathomechanisms, which will be discussed in this review. PMID- 11771448 TI - [NO-synthase and cardiovascular gene therapy]. AB - Molecular biology research of vascular remodeling paved the way to novel therapeutic approaches in experimental cardiology. Using gene transfer methods in various animal models, it has been shown that overexpression of nitric oxide synthase (NOS) can inhibit neointimal lesion proliferation. This review summarizes pivotal data regarding NO synthase gene manipulation in the cardiovascular system which enabled transition of this experimental approach from the bench to the clinical arena. PMID- 11771449 TI - [Value of training-induced effects on arterial vascular system and skeletal muscles in therapy of NYHA II/III heart failure]. AB - Dynamic muscular exercise performed by healthy subjects leads to a rise in the left ventricular blood ejection with an acute increase in the local wall shear stress on the endothelium of the arterial vessels. These hemodynamic changes results in a release of endothelium-dependent relaxing factors, one of them concerns nitric oxide (NO). Therefore an arterial vasodilatation with an acute increase in the blood flow volume to the exercising muscle groups occurs. If more than 1/6 of the skeletal musculature is involved in exercise and if training duration exceeds 3-5 hours a week the chronically increased blood flow volume in the cardiovascular system triggers structural and functional changes of the heart and the arterial vessels. It develops a functional intact excentric hypertrophy of the myocardium; within the arterial vessels an increase in the diameter of the muscular arteries supplying the trained muscle groups occurs. These training induced adaptations of the cardiovascular system are adjusted to improve the aerobic skeletal muscle metabolism. In congestive heart failure a pathological excentric myocardial hypertrophy is found. In this case the systolic myocardial function is impaired and the left ventricular ejection fraction is reduced already in early stages, so that the cardiac output can not be sufficiently increased during exercise. In addition a dysfunction of the endothelium of the arterial vessels occurs. As a consequence the endothelium-dependent arterial vasodilation is reduced, so that the peripheral arteries could not supply the muscle groups involved in exercise with enough blood flow volume. Therefore, the acute delivery of the working musculature with oxygen and energy substrates is insufficient, so that premature muscular fatigue occurs. The reduced exercise resistance of the patients leads chronically to a generalized skeletal muscle atrophy. Ultrastructural analysis revealed a decrease of oxidative type 1 muscle fibers with a relative increase of more glycolytic type 2 fibers. In addition, the volume density and the surface area of the cristae of mitochondria are reduced. All these changes results in a decrease of aerobic skeletal muscle metabolism independent of the blood flow volume, so that the physical fitness of the patients progressively decline. On the basis of the training-induced physiological adaptations of the cardiovascular system, a special exercise therapy supervised by a physician was developed for patients with congestive heart failure NYHA II/III. It have been shown that various exercise programs, which are adjusted to the degree of cardiac function impairment are suitable to restore the endothelial dysfunction of the arterial vessels as well as to cure the disturbed skeletal muscle metabolism in these patients independent of an improvement of cardiac function. Therefore in patients with congestive heart failure NYHA II/III who underwent regularly such an exercise therapy, the secondary impaired physical fitness could be rebuild without an excessive risk for an acute exercise-induced cardiovascular emergency. PMID- 11771450 TI - [Comparison of various parameters for determining an index of myocardial perfusion reserve in detecting coronary stenosis with cardiovascular magnetic resonance tomography]. AB - For the assessment of myocardial perfusion with cardiac magnetic resonance imaging, different semiquantitative parameters of the first pass signal intensity time curves can be calculated and myocardial perfusion reserve indices can be determined. In this study we evaluated the feasibility of different perfusion parameters and their perfusion reserve indices for the detection of significant coronary artery stenosis. The signal intensity time curves of the first pass of a gadolinium-DTPA bolus injected via a central vein catheter before and after dipyridamole infusion were investigated in 15 patients with single vessel (stenosis > or = 75% area reduction) and five patients without significant coronary artery disease. For the distinction of ischemic and nonischemic myocardial segments, semiquantitative parameters, such as maximal signal intensity, contrast appearance time, time to maximal signal intensity and the steepness of the signal intensity curve's upslope determined by a linear fit, were assessed after correction for the input function. For each parameter a myocardial perfusion reserve index was calculated and cut off values for the detection of significant coronary stenosis were defined. The diagnostic accuracy of each parameter was then examined prospectively in 36 patients with coronary artery disease and compared with coronary angiography. Where as a distinction of ischemic and normal myocardium was possible with myocardial perfusion reserve indices, semiquantitative parameters at rest or after vasodilation alone did not allow such a distinction. The perfusion reserve index calculated from the upslope showed the most significant difference between ischemic and nonischemic myocardial segments (1.19 +/- 0.4 and 2.38 +/- 0.45, p < 0.001) followed by maximum signal intensity, time to maximum signal intensity and contrast apperance time. Sensitivity, specificity and diagnostic accuracy was 87, 82 and 85% for the detection of hypoperfusion induced by significant coronary artery stenoses using the perfusion reserve index calculated from the upslope. The steepness of the first pass signal intensity curve's upslope, determined by a linear fit, is a feasible parameter for the detection of significant coronary artery disease with MR. Based on a myocardial perfusion reserve index of this parameter, ischemic myocardium can be identified with high diagnostic accuracy. PMID- 11771451 TI - [Assessing myocardial perfusion with positron emission tomography]. AB - Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive study. The cost of PET in combination with the cost of a cyclotron facility together with the demanding methological problems have limited the availability of perfusion PET to a few sophisticated centers. Therefore, quantitative PET investigations of myocardial perfusion have been performed predominantly for scientific purposes, and the cost-effectiveness of PET in the everyday clinical setting is not yet finally proven. However, the unique possibilities of PET to study non-invasively and quantitatively myocardial perfusion and metabolism as well as cardiac innervation and pharmacokinetics of cardiac drugs have established cardiac PET as a scientific tool of the highest quality for the future. PMID- 11771452 TI - [Determining myocardial perfusion--contribution of contrast echocardiography]. AB - There is great demand for a non-radioactive bed-side method for the assessment of myocardial perfusion by contrast echocardiography, which may gain clinical relevance for diagnostic strategies only with i.v. application of the contrast agent as opposed to the intracoronary application used until recently. This has finally become true after many years of developing left heart contrast agents and more adequate ultrasound acquisition methods. This leads to the question: Where are we now? Myocardial contrast echocardiography yields unique information on the pathophysiology of microcirculation in vivo due to the fact that microbubbles remain strictly intravascular. Experimental and clinical studies using intracoronary contrast application have shown that infarct size and area at risk are depicted with high accuracy and furthermore that reflow vs no reflow phenomena are demonstrated after the revascularization procedure. In addition, presence and prognostic implications of collateralization may be assessed. Microvascular integrity plays an important role for functional recovery after revascularization. The breakthrough to a potentially clinical role of contrast echocardiography is mainly due to the development of new acquisition methods, such as pulse inversion technique, which allow differentiation of the microbubble signature from the surrounding myocardium. Initial publications show good diagnostic accuracy for the assessment of infarct size and area at risk as well as for the reflow vs no reflow phenomena and microvascular integrity, in particular also as follow up after protective interventions to improve microcirculation. Now, it is conceivable to assess relative or absolute changes of myocardial perfusion. This may be achieved by using non-video signals for analysis and by understanding attenuation effects and other artifacts. Further intensive and critical evaluation and standardization of imaging and analysis techniques is required before general clinical acceptance. New insight into the dynamic nature of perfusion, however, may already allow progress in some urgent questions of microvascular protection. PMID- 11771453 TI - [Quality of life after aortic valve replacement. Self-management or conventional anticoagulation therapy after mechanical valve replacement plus pulmonary autograft]. AB - BACKGROUND: The improvement of quality of life gains increasing importance for the judgement of operative techniques. Besides the commonly used mechanical substitutes or bioprostheses for aortic valve replacement, the interest in the Ross procedure is growing. The aim of the study was to compare the quality of life after the Ross procedure with that after mechanical aortic valve replacement with two different anticoagulation regimes (self-management or conventional therapy). METHODS AND RESULTS: Clinical, echocardiographic and quality of life investigations (SF-36) were performed in patients with mechanical aortic valve replacement and self-management of anticoagulation (group A, n = 20) or conventional anticoagulation therapy (group B, n = 20) and in patients after the Ross procedure (group C, n = 20). The mean ages were 59.5 +/- 9.2 (group A), 61.2 +/- 8.1 (group B) and 59.3 +/- 9 years (group C). Significantly lower values of quality of life (SF-36) were observed in group B compared with group A (5 of 9 subtests) and with group C (6 of 9 subtests) and also in the physical and mental health sum scales. CONCLUSION: In this study the quality of life in patients after the Ross procedure and similarly after mechanical valve replacement and self-management of anticoagulation is superior to the quality of life after mechanical valve replacement and conventional anticoagulation. PMID- 11771454 TI - [Perforated mitral valve aneurysm as a rare course of bacterial endocarditis]. AB - A 65 year old man with a history of mechanical aortic valve replacement acquired Enterococcus faecalis mediated infective endocarditis about 3 years later. Transesophageal echocardiography revealed formation of an aneurysm confined to the anterior mitral valve leaflet. The aortic valve revealed no signs of endocarditis by transesophageal ultrasound. With sudden perforation of the mitral valve aneurysm, subsequent hemodynamic deterioration and pulmonary oedema, the patient underwent emergency mitral and aortic valve replacement. The postoperative course was uneventful. PMID- 11771455 TI - [Papillary fibroelastoma of the aortic valve--a rare cause of thromboembolic cerebral infarct]. AB - We report on a case of papillary fibroelastoma of the aortic valve in a 55 year old female patient, who had thrombembolic complications and subsequent stroke. The tumor was resected without disturbing the structure and function of the aortic valve. PMID- 11771456 TI - [Position paper on intracoronary brachytherapy]. PMID- 11771457 TI - Comparing the most current health information across states. PMID- 11771458 TI - Buttons, buttons, and more buttons: are they professional? PMID- 11771459 TI - Leadership development for the new manager in the small, acute care facility. PMID- 11771460 TI - The impact of healthcare reform on paradise: a statewide assessment of Hawaii's acute care hospitals. PMID- 11771461 TI - Understanding Net Generation employees. AB - The Net Generation is the digitally-savvy generation born between the years of 1980 and 1999. People born during this time are predicted to seek careers in the helping professions, be open to job stability and working in organizations, and intolerant of coworkers and leaders who are not technically competent. The Net Generation persona and its work-related skills and values are explored and implications are posed in this article for nurse administrators. PMID- 11771462 TI - RN internship: outcomes of a one-year pilot program. AB - Faced with a threatened shortage of highly skilled, acute care pediatric nurses, an RN Internship in Pediatrics program for new graduates was brought from vision to reality. Goals of the program were to: 1) facilitate transition of the new graduate nurse to professional registered nurse (RN); 2) prepare a beginning level staff nurse who is confident and who provides competent and safe patient care; and 3) increase the commitment and retention of new graduate nurses within the organization. A 1-year pilot program evaluation demonstrated that the interns who had an average of 8 months of RN experience were comparable or better on all measures than were control group participants who obtained up to 2 years of RN experience. A return on investment of 67.3% was established. PMID- 11771463 TI - Research in the community hospital. AB - Research is an essential component in professional nursing practice. Although nursing research efforts have increased, there is little evidence of a consistent infrastructure within the community hospital to promote research utilization and the conduct of nursing research. There are multiple mechanisms for nurse administrators to support research efforts in the community hospital. We discuss the value of research and research utilization in the community hospital and suggest some practical strategies for nurse administrators to support research efforts. PMID- 11771464 TI - Hospital restructuring and its impact on outcomes: nursing staff regulations are premature. AB - OBJECTIVE: Describe restructuring in the organization and delivery of patient care and the effects of nursing structure and processes on selected patient outcomes. BACKGROUND: Restructuring has been the dominant cost-reduction strategy in acute care hospitals. Changes occurred without a systematic look at how interventions impacted on the processes and outcomes of care. METHODS: Twenty nine university teaching hospitals participated. Uniform structure, process, and outcome data were collected from each hospital and its study, medical, and surgical units. Outcome data included fall rate, nosocomial pressure ulcer, and urinary tract infection rates and patient satisfaction scores. RESULTS: RNs were fewer in number, with an increase in Unlicensed Assistive Personnel. Outcomes were affected by registered nurse hours worked per patient/day and hours worked per patient day by all staff and their interactions with processes. Increased registered nurse hours worked per patient/day were associated with lower fall rates and higher patient satisfaction levels with pain management. Increased hours worked per patient day by all staff were associated with lower urinary tract infection rates. CONCLUSIONS: Data from this study do not enable specific staffing recommendations. Expanded hospital and unit level data should be collected and reported annually. Nursing staff regulations should be deferred until expanded structure and outcome data from all acute care hospitals are systematically collected, reported, and analyzed. PMID- 11771466 TI - Walking our homebound patients through terror, grief, and loss. PMID- 11771467 TI - A look to the future: how emerging information technology will impact operations and practice. AB - The use of information technology tools in home care delivery is dramatically increasingly. This technology can streamline business and clinical processes by linking people with one another and to vital healthcare information at any time, any place. This article describes four emerging information technology trends that are currently influencing home care nursing and presents future implications. PMID- 11771468 TI - Critical steps for integrating information technology in home care: one agency's experience. AB - Complying with Medicare PPS mandates that agencies upgrade their information systems to integrate operations, clinical delivery, and billing functions including point-of-care technology. The critical steps of selecting and implementing information systems and components of agency analysis needed prior to employing information technology--are presented in this article. The author uses her agency's experience as a reference point. PMID- 11771469 TI - Point-of-care training: strategies for success. AB - In most cases, the resources and time required for training staff in a POC integrated computer system are underestimated. Based on the authors' consulting and training experiences, particularly with an early POC installation at a large VNA, key strategies for the design, implementation, and evaluation of a POC training program are presented. PMID- 11771470 TI - Home care patients' responses to point-of-care technology. AB - Patient response is a critical aspect of successful POC technology implementation. This article presents the results of a pilot POC patient satisfaction study conducted at four home health agencies. Variables impacting patient receptiveness and recommendations for patient education are discussed to help agencies develop individual POC training and education plans. PMID- 11771471 TI - Reflections from a point-of-care pilot nurse group experience. AB - Home care agencies often fail to commit adequate resource time preparing nurses for POC technology. Successful implementations need to incorporate human issues in addition to the technical aspects for POC. This article discusses the experiences and perceptions of nurses who participated in a pilot POC training group. The pilot group and key elements of the training are presented. The results of a focus group present the major POC focus of importance for the nurses. PMID- 11771473 TI - Thermal and water relations of desert beetles. AB - The physical problems that living organisms have to contend with in hot deserts are primarily extremes of temperature, low humidity, shortage or absence of free water, and the environmental factors that accentuate these--such as strong winds, sand-storms, lack of shade, rocky and impenetrable soils. Climatic factors are particularly important to smaller animals such as arthropods on account of their relatively enormous surface to volume ratios. Nevertheless, beetles (especially Tenebrionidae and, to a lesser extent, Chrysomelidae) are among the most successful animals of the desert, and are often the only ones to be seen abroad during the day. Similar physical problems are experienced by insects in all terrestrial biomes, but they are much enhanced in the desert. Although climatic extremes are often avoided by burrowing habits coupled with circadian and seasonal activity rhythms, as well as reproductive phenology, several species of desert beetle are nevertheless able to withstand thermal extremes that would rapidly cause the death of most other arthropods including insects. The reactions of desert beetles to heat are largely behavioural whilst their responses to water shortage are primarily physiological. The effects of coloration are not discussed. In addition to markedly low rates of transpiration, desert beetles can also withstand a considerable reduction in the water content of their tissues. The study of desert beetles is important because it illustrates many of the solutions evolved by arthropods to the problems engendered, in an extreme form, by life in all terrestrial environments. PMID- 11771472 TI - Health tips for computer users. AB - Computers have changed everything about our world. Any change of this magnitude brings new challenges and new concerns for the long-term effects of exposure to the product. Computers especially pose specific risks to home care workers. This article reviews health and safety practices related to desktop and hand-held computers. PMID- 11771475 TI - A "spare" compensates for the risk of destruction of the elongated penis of earwigs (Insecta: Dermaptera). AB - Male animals in several groups have multiple intromittent organs that outnumber the corresponding female gonopore. In Dermaptera (earwigs), males of the family Anisolabididae have paired, elongated male intromittent organs (virgae), while females have a single sperm-storage organ (spermatheca). Several authors have assumed that one of the paired virgae is non-functional, because it points in the "wrong" direction. We investigated the mating success of handicapped males of Euborellia plebeja in which one of their paired virgae was removed experimentally. These handicapped males succeeded in inseminating a mate. Males with genital damage are found in the field, suggesting that the "spare" functions under natural conditions. Based on phylogenetic information on earwigs, we discuss possible evolutionary scenarios for this genital peculiarity. PMID- 11771476 TI - Visualizing mushroom body response to a conditioned odor in honeybees. AB - Combining differential conditioning with optophysiological recordings of bee brain activity allows the investigation of learning-related changes in complex neural systems. In this study we focused on the mushroom bodies of the bee brain. Presenting different odors to the animal leads to significant activation of the mushroom body lips. After differential conditioning, the rewarded odor leads to stronger activation than it did before training. Activation by the unrewarded odor remains unchanged. These results resemble findings in the bee's antennal lobes, which are the first olfactory relay station in the insect brain. As an integrative neural network, enhanced activation of the mushroom body lip may carry additional information, i.e., for processing odor concentrations. PMID- 11771477 TI - Retinal regionalization and heterogeneity of butterfly eyes. AB - The regional characteristics of the eyes of butterflies from different families have been surveyed using epi-illumination microscopy, utilizing the eyeshine visible due to the tapetum situated proximally to the rhabdom. All butterflies studied have a high spatial acuity in the frontal region. The facet diameter varies slightly across the eye, and the interommatidial angle and the eye parameter p are especially large dorsally. Whereas the ommatidial lattice is generally highly regular, the eyeshine colours distinctly depend on the species. Sometimes the eyeshine is locally uniform, but often it is heterogeneous. It is hypothesized that the regional characteristics as well as the local heterogeneity are adaptations that optimize spectral discrimination. PMID- 11771478 TI - Innate immune reactions stimulated by a lipopolysaccharide-like component of the alga Prototheca (strain 289). AB - We report on the influence of an LPS-like molecule (aLPS) from the pathogenic alga, Prototheca (strain 289) on insect and murine innate immune reactions. Insect innate reactions to infection include nodule formation, a process of entrapping bacterial cells in aggregates of hemocytes. We recorded eicosanoid dependent, dose-related nodulation reactions to aLPS in hornworms (Manduca sexta). The insect reaction was attenuated by pre-incubating the aLPS with polymyxin-B. Conversely, the murine macrophages reacted to challenge with Escherichia coli LPS by secreting cytokines, but did not react to aLPS. We infer that, while highly conserved with respect to intracellular mechanisms of interaction, insect and mammalian immune surveillance systems differ in recognition of LPS molecular types. PMID- 11771479 TI - History of the Voluntary Initiative Program. PMID- 11771480 TI - Delaware's uninsured. PMID- 11771481 TI - Improving access to care for the uninsured: lessons from across the nation. PMID- 11771482 TI - Systemic vasculitis--Part II. Specific diseases. PMID- 11771483 TI - Bioterrorism, physician education, and the Internet. AB - To meet the challenges of bioterrorism, the practicing physician must have information that is authoritative, specific, and timely with respect to any outbreaks or suspected outbreaks of bioterrorism. Educational activities for physicians and other health care workers are important. In the United States, bioterrorism was not an issue until October 2001, and bioterrorism disease organisms are not ones commonly dealt with in civilian health care. Web sites that satisfy these information and educational requirements are discussed. PMID- 11771484 TI - Is anthrax the next Lyme disease? PMID- 11771485 TI - Covenants not to compete. PMID- 11771487 TI - Lead poisoning--a serious public health issue for Iowa's children. PMID- 11771488 TI - Medicaid and Medicare still top priorities. PMID- 11771486 TI - Biological and chemical terrorism--are we prepared? PMID- 11771489 TI - Bringing FAIR-ness to Medicare reimbursement rates. PMID- 11771490 TI - TIPSSing the scales for patients with cirrhosis. PMID- 11771491 TI - Akathisia--a brief review. PMID- 11771492 TI - Frequency of continuing mucosal inflammation in clinically inactive Crohn's disease. AB - The treatment goal in Crohn's disease is clinical remission, not complete mucosal healing. The incidence of mucosal inflammation in Crohn's disease patients in clinical remission is not known. Whole gut lavage is an objective method of assessing mucosal inflammation. We aimed to assess levels of mucosal inflammatory activity in a group of patients with clinically inactive Crohn's disease. We prospectively assessed 30 patients with inactive Crohn's disease and 28 controls. Inactive disease was defined as Crohn's disease activity index of less than 150. All underwent whole put lavage, with analysis of whole gut lavage fluid IgG, haemoglobin, interleukin-1 beta, interleukin-8 and granulocyte elastase. Serum inflammatory parameters were collected for comparison. Of the 30 patients with Crohn's disease, 10 (33%) had an abnormal immunoglobulin G, 21 (70%) had an elevated interleukin-1 beta 20 (66%) interleukin-8 and 10 (33%) granulocyte elastase in the whole gut lavage fluid. 58% of patients had either 1 or 2 abnormal results. In contrast only 10% had 1 or 2 abnormal serum results. Few abnormalities were present in lavage fluid or serum of the control population. We concluded that ongoing mucosal inflammation is detectable in whole gut lavage fluid of up to 2/3 of Crohn's disease patients in clinical remission. PMID- 11771493 TI - Opinions of patients and the public regarding NHS priorities. AB - The purpose of this study was to ascertain the views of patients and the public on NHS priorities. Data were gathered by interview questionnaire throughout Edinburgh city centre, and within various departments of one large teaching hospital. Of the 1502 responses, 462 were from within the hospital and 1040 were from city centre locations. 1497 (99.7%) were in favour of treating emergencies, and 1467 (97.7%) life threatening conditions as a priority. 1315 (88%) agreed that treatable conditions that seriously affect quality of life should also be considered a priority and 1127 (75%) were in favour of treating patients with incurable terminal disease regardless of cost. In order to provide these services 584 (39%) considered it acceptable to make patients with less serious conditions wait longer. Of the 918 (61%) who considered it not acceptable to wait longer 812 (88%) would be prepared to pay more in tax to provide this. The General Public do support the treatment of emergency and life threatening conditions as an absolute priority. The majority also support the prioritization of conditions which are treatable and seriously affect quality of life. If in establishing these priorities waiting times for other conditions are likely to rise, the public would generally accept increased taxation or some form of fee for service. PMID- 11771494 TI - The role of dihydrocodeine in causing death among drug users in the west of Scotland. AB - There has been a wealth of information relating to the role of methadone in fatalities over the past decade. However, a dearth exists in the literature of deaths involving dihydrocodeine, a substitute that is being increasingly prescribed by general practitioners for drug harm reduction purposes. Over the past five years in the Strathclyde region of Scotland there has been an increase in the number of drug related deaths involving dihydrocodeine with the largest increase occurring in the latter two years. This in combination with a general acceptance for this drug as a substitute for methadone amongst general practitioners highlights its potential abuse factor which is addressed in this paper. As the number of methadone deaths in relation to the total number of accidental drug related deaths per annum decrease, those related to dihydrocodeine are shown to be increasing. PMID- 11771495 TI - Severe abdominal pain in women: a case report of an hepatic adenoma. AB - As the use of the oral contraceptive pill increases, so does the incidence of hepatic adenomata. This condition can present as an acute surgical emergency in the previously healthy female but is often overlooked as a possible diagnosis. This report illustrates such a case and its sometimes unusual presentation. PMID- 11771496 TI - Coronary sinus pacing in an elderly patient with Bjork-Shiley tricuspid valve replacement. AB - We report the first case of permanent pacing via the coronary sinus in a patient with a Bjork-Shiley tricuspid valve replacement. This may be the route of choice in this group of patients. PMID- 11771497 TI - Lymphangioleiomyomatosis. A series of three case reports illustrating the link with high oestrogen states. AB - Lymphangioleiornyomatosis is a rare lung disorder characterised by cystic air spaces and smooth muscle proliferation. The condition, which most commonly presents with dyspnoea, pneumothoraces or cough, is only described in females and is most commonly diagnosed during childbearing years. Three cases are presented which illustrate typical features of the disease and the association with high oestrogen levels. The first had recurrent pneumothoraces during her first pregnancy. The second lady was post menopausal at diagnosis but her symptoms predated her menopause. The third, presented with dyspnoea, abnormal chest sensations and a pneumothorax. She had a history of hyperprolactinaemia with secondary amenorhoea due to low oestrogen levels which had been corrected prior to her presentation. All three patients had reduced gas transfer and abnormalities in spirometry, two had reticular shadowing on their chest radiograph and all had typical appearances on lung computerised tomography. Although disease progression was variable, all patients showed a gradual decline in lung function. PMID- 11771498 TI - Superior mesenteric artery syndrome in children. AB - Superior mesenteric artery syndrome is an uncommon clinical condition characterised by features of acute or chronic upper gastrointestinal tract obstruction. It sometimes has particular clinical associations such as weight loss, spinal surgery cast application or adhesions. Associated multiple clinical problems can complicate the picture and delay diagnosis. Diagnosis is usually by barium meal showing compression of the 3rd part of duodenum. Treatment can be conservative or surgical. Surgical treatment consists of division of the ligament of Treitz and derotation of the gut. We review our experience of four children with this syndrome. PMID- 11771499 TI - Recurrence of breast cancer following local excision alone for ductal carcinoma in situ. PMID- 11771500 TI - Bibliography. Current world literature. General obstetrics. PMID- 11771501 TI - Being too thin could increase risk for heart disease. PMID- 11771502 TI - Cigarette smoking damages right coronary artery. PMID- 11771503 TI - Women behind men in treatment, awareness of heart disease. PMID- 11771504 TI - Bibliography. Current world literature. Neuro-ophthalmology. PMID- 11771505 TI - Bibliography. Current world literature. Ocular manifestations of systemic disease. PMID- 11771506 TI - [The "Hortulus" of Valafridus Strabus from the IX-th century: one of the oldest documents of the medieval knowledge of herb-growing]. AB - Valafridus Strabus, the author of the Latin poem entitled Hortulus (The Little Garden), lived in the Caroline epoch. He was a German monk and a poet and, for some time, he was connected with the famous Benedictine abbey at St. Gallen, which had a garden with curative herbs. He dedicated his best work, The Little Garden, to Grimaldus, the abbot of St. Gallen who was his master and teacher. This work, written in 444 hexameters, consists of 26 chapters which contain descriptions of 23 herbs such as sage, rue, lovage, mint and others. Apart from herbs, there are also descriptions of some vegetables grown in the monastery gardens, such as pumpkin, melon and celery. "The Little Garden" is one of the oldest and most highly valued documents of the medieval knowledge of herb-growing and their curative properties. It also gives us an idea of the arrangement of the medieval monastery garden in which herbs were grown. PMID- 11771507 TI - [Jan Kasprowicz's pattern of health and the cause of his death]. AB - Jan Kasprowicz, one of the greatest Polish poets, was born in Szymborze, near Inowroclaw 1860. In his youth he often suffered from throat and upper respiratory track infections. When he was 64 he fell ill with diabetes and a stroke and hemiparesis. Insulin treatment in Lvow's clinic improved his condition, last two years later he suffered from an infarct, circulatory failure and arrhythmia. Progressive illness caused the poet's death on the 1st August 1926. PMID- 11771508 TI - Transition plan is key to credit. PMID- 11771509 TI - Exec recruiters: try vendors. PMID- 11771510 TI - Docs on top. PMID- 11771511 TI - Talent is here. Use it. PMID- 11771512 TI - Good leaders attract good staff. PMID- 11771514 TI - To tell the truth. PMID- 11771515 TI - 1Q[3a]. What area of the Internet holds the most promise? PMID- 11771513 TI - Hospitals need new world view. PMID- 11771516 TI - At a loss for words. PMID- 11771519 TI - Molecular classification of human diffuse gliomas by multidimensional scaling analysis of gene expression profiles parallels morphology-based classification, correlates with survival, and reveals clinically-relevant novel glioma subsets. AB - There are several currently employed classification systems for diffuse gliomas that sort tumors based on histological features. Contemporary molecular techniques, however, offer the promise of improved tumor classification and resultant patient stratification for treatment and prognosis. In particular, gene expression profiling has shown exceptional promise for providing an alternative and more objective molecular approach to glioma classification. In this study, we used cDNA array technology to profile the gene expression of 30 primary human glioma tissue samples comprising 4 different glioma subtypes as defined by current World Health Organization (WHO 2000) criteria: glioblastoma (GM, WHO grade IV), anaplastic astrocytoma (AA, WHO grade III), anaplastic oligodendroglioma (AO, WHO grade III), and oligodendroglioma (OL, WHO grade II). Gene expression data alone were used to group the tumors using multidimensional scaling, which is an unsupervised statistical method. Results show that impressive separation of the 4 glioma subtypes can be achieved solely on the basis of molecular data. In addition, a subcluster of 3 glioblastomas was identified as distinct from other GMs and from the oligodendroglial tumors. These 3 patients have shown extended survival compared to other GMs in the study. Survival analysis of the full data set revealed a good correlation with the molecular classification. Results of this proof-of-principle study demonstrate that molecular profiling alone can recapitulate conventional histologic classification and grading with high fidelity. In addition, results show that the molecular approach to tumor classification can generate clinically meaningful patient stratification, and, more importantly, is an efficient class-discovery tool for human gliomas, permitting the identification of previously unrecognized, clinically relevant tumor subsets. PMID- 11771520 TI - A method to reduce the number of measured parameters when using isokinetic muscle strength as a clinical indicator in rheumatoid arthritis patients. AB - The aim of the study was to present a method enabling a reduction of the number of measurements when quantifying isokinetic muscle strength (IMS), and to describe an expression for IMS which is independent of measuring conditions. IMS is a measure of muscle strength used to categorise patients and to assess changes over time. IMS measurements involve one or several measures of peak torque at different chosen angular velocities. Comparisons between studies are difficult and an expression of IMS independent of measuring conditions is needed. Thirty six women with rheumatoid arthritis were followed for 1 year. IMS was measured on five occasions on both knees at seven angular velocities, giving 10 sets of peak torque data for each patient. The log[peak-torque]-angular-velocity diagram showed a linear relationship. From this, the peak-torque value at the chosen angular velocity of 30 degrees/s (IMS30) was estimated for each test and the uncertainties involved were quantified. IMS30 is a reliable parameter when comparing effort between knees, visits and patients, and may be based on three sets of data only. IMS may be expressed by a single value, IMS30, representing the fitted line in a log[peak-torque]-angular-velocity diagram. The regression line may be fitted by three or more angular velocities. In principle, IMS30 is independent of the chosen angular velocity, which makes it possible to use an estimated value as IMS30 to compare results, studies and centres in between. PMID- 11771521 TI - Factors associated with anxiety, depression and suicide ideation in female outpatients with SLE in Japan. AB - The subjects consisted of 84 female SLE outpatients who were all over 20 years of age. These patients were able to maintain relatively stable physical conditions and lead normal daily lives, and they were regularly treated at the outpatient clinic. All subjects were Japanese. Psychological features (trait anxiety, state anxiety, depression and suicide ideation) were evaluated using psychological tests, and the relationships between the respective psychological features and background factors were statistically evaluated using stepwise multiple logistic regression analyses. In this study, we found that 'the self-evaluation of not having understood SLE at the time of starting SLE treatment' was the background factor significantly affecting depression or trait anxiety. 'No spouse' had a statistically significant effect on depression, and 'self-awareness as problems of side-effects due to steroids' had a statistically significant effect on state anxiety. We also found 'human relations among family members' and 'high daily steroid dosage' to be significantly correlated with suicide ideation. However, there were no correlations between the psychological features and 'disease activity at the time of investigation' or 'history of neuropsychiatric diseases'. In female SLE outpatients, performing psychological approaches focusing on 'understanding SLE at the beginning of treatment', 'the human relationships among family members', or 'issues related to steroid therapy' may be useful for the early treatment or prevention of various major mental problems. PMID- 11771522 TI - Hormonal responses to exercise stress test in patients with fibromyalgia syndrome. AB - Twenty patients with fibromyalgia syndrome (FMS) and 20 matched healthy controls were subjected to an exercise stress test above their anaerobic threshold. Serum samples for the measurement of growth hormone (GH), insulin-like growth factor-1 (IGF-1), prolactin (PRL), adrenocorticotrophic hormone (ACTH) and cortisol were taken prior to and after the test at 30-min intervals. Compared to the controls, the patients with FMS displayed significantly lower basal GH levels and slightly, though significantly, higher prolactin levels. Following the exercise test there was a significant increase in the mean GH level in the patient group (P = 0.0474) and a significant decrease in the control group (P = 0.0286) 1 hour after the exercise. A slight decrease in ACTH levels in the control group was observed (P = 0.0002), but there was no significant change in FMS patients. Cortisol levels were significantly lower in both groups after the exercise (P = 0.0001). These results suggest the possibility of a perturbation in hormonal response to exercise in patients with FMS. PMID- 11771523 TI - Toxicity of methotrexate treatment in psoriasis and psoriatic arthritis--short- and long-term toxicity in 104 patients. AB - Methotrexate (MTX) is an effective anti-psoriatic agent but there are major concerns about its long-term toxicity, in particular to the liver. Reported frequencies and recommendations for monitoring patients on MTX vary considerably. The aim of this study was to analyse the frequency and severity of MTX-associated adverse drug reactions (ADR) in patients with psoriasis and psoriatic arthritis. A retrospective analysis was performed of 104 psoriasis and psoriatic arthritis patients (60 male, 44 female) treated with MTX between October 1968 and October 1998. The severity of ADR was classified according to Common Toxicity Criteria (CTC). Acute ADR was defined as adverse effects within the first 90 days of MTX therapy. ADR seen later were classified as chronic. In 83 patients 165 ADR were noted within the beginning of MTX therapy. In five patients treatment was terminated because of ADR. During long-term therapy 23 patients received < or = 2000 mg MTX (group A); 81 received a cumulative dose greater than 2000 mg (group B). The total frequency of ADR in group B and the frequency of ADR CTC grade 3 or 4 in general was not significantly increased in group B (chi2 test; P = 0.468). Group B was characterised as follows: CTC grade 3 or 4 blood count changes led significantly more often to the termination of MTX (Fisher's exact test; P = 0.048), CNS side-effects (P = 0.016) and infections were more frequent (chi test; P<0.001). Liver changes and serum enzyme level increases were not significantly more frequent in group B. ADR are common in psoriasis patients on MTX therapy independent of the cumulative dose. In most cases they are temporary by nature and mild. Liver changes and serum enzyme level increases were not a major problem in our patients. PMID- 11771524 TI - Adenosine deaminase activity and its isoenzyme pattern in patients with juvenile rheumatoid arthritis and systemic lupus erythematosus. AB - Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3 nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity. PMID- 11771526 TI - Polymorphsims of CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in spondyloarthropathies. AB - The aim of the study was to investigate a possible association between the CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 and spondyloarthropathies (SpA). Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in 54 SpA patients, 84 healthy control subjects and 87 bronchial asthma patients as disease controls. There were no significant differences in the genotype and allele frequencies of the CTLA-4 exon 1, promoter and Fas promoter genes among SpA, asthma patients and controls. No significant differences were found in age at onset, sex, disease duration, history of enthesopathy, peripheral arthritis and uveitis, Schober test, chest expansion, white blood cell count, C-reactive protein and erythrocyte sedimentation rate among patients with SpA according to the CTLA-4 exon 1, CTLA-4 promoter and Fas promoter polymorphisms. We found no association between the polymorphisms of the CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter 670 genes and SpA. However, further studies are required to discover the possible contribution of the polymorphisms of the CTLA-4 and Fas to the pathogenesis of SpA. PMID- 11771525 TI - Japanese generalised osteoarthritis was associated with HLA class I--a study of HLA-A, B, Cw, DQ, DR in 72 patients. AB - To investigate the association between generalised osteoarthritis (GOA) and HLA A, B, Cw, DQ and DR, we typed for HLA in 72 Japanese patients with GOA and compared with those of 1480 normal controls. The antigen frequency of HLA-Cw4 was significantly higher in the GOA group than in the control group. That of B62 was higher, but only uncorrected P values were significant. Those of HLA-Cw1 and Cw10 were significantly lower in the GOA group than in the control group. The antigen frequencies of HLA-DRB1*0101, *0401, *0405, *1001, and *1402, which were reported to be associated with rheumatoid arthritis, in the GOA group were not significantly different from those in the control group. The present study provides evidence of a significant association between Japanese GOA and HLA, which is different from that of Japanese RA. This may suggest that an immunological reaction that is different from RA plays a role in the pathogenesis of GOA. PMID- 11771527 TI - Use of isokinetic muscle strength as a measure of severity of rheumatoid arthritis: a comparison of this assessment method for RA with other assessment methods for the disease. AB - The aim of this study was to study the association between isokinetic muscle strength (IMS) and other clinical indicators of disability and disease activity in patients with rheumatoid arthritis (RA). A cohort of 36 RA patients was followed over a 1-year period with five measurements of disease activity at regular intervals during this time. IMS was measured at seven angular velocities in both knees, on five separate occasions. The measurement was expressed by the level of the fitted line of the seven peak torque values--IMS30. The association between IMS30 and clinical indicators was stated. As an indicator of disability the score from the Stanford Health Assessment Questionnaire (HAQ) was used. As indicators of disease activity morning stiffness, an index of swelling and pain in the joint, erythrocyte sedimentation rate (ESR) and haemoglobin (Hb) were chosen. Larsen's X-ray score was used as an indicator of bone destruction due to longer-lasting disease activity. IMS was significantly associated with the HAQ score, but not with indicators of disease activity or radiological findings. IMS was significantly associated with changes in indicators of disease activity, but not with the changes in the HAQ score, or in the X-ray-score. IMS showed the strongest association with changes in the degree of arthritis of the knee. In conclusion, IMS was associated with the HAQ score and can therefore be used when measuring outcome in a specific group of RA patients. Changes in IMS were associated with indicators of changes in disease activity, and are therefore usable as a measure of patient outcome. Of particular importance is that IMS decreased if a patient developed active arthritis in the knee, and normalised again when the inflammation decreased. PMID- 11771528 TI - Local deposition of calcium pyrophosphate crystals in evolution of knee osteoarthritis. AB - The aim of the study was to investigate the frequency of development of local calcium pyrophosphate (CPPD) crystal deposition in patients with knee OA initially found negative for these crystals, as well as to discover whether prognostic indicators for this subset of patients can be found. A clinical follow up of records of outpatients with idiopathic knee OA was established. An anteroposterior plain radiography of the knee joints was made initially and at the end of the observation period. The follow-up period needed to be more than 1 year. Patients were divided into two groups. The first included patients with knee OA who did not develop intra-articular CPPD crystal deposition during the observation period (OA group). The second included those patients whose X-rays or synovial fluid (SF) analysis in the follow-up showed these crystal deposits to be present (OA + CPPD group). There were 59 patients (42 women, 17 men) who met the selection criteria. During the observation period (8.1 + 7.4 years in the OA group, 10.4 +/- 6 years in the OA + CPPD group), intra-articular CPPD deposits were observed in 15 patients (25%): 10 on the X-rays, eight in the SF and three in both examinations. Age at diagnosis of OA and incidence of obesity were similar in both groups. There was a trend (P = 0.21) towards men developing intra articular CPPD crystal deposits more frequently than women. OA in only one knee joint was significantly more frequent in the group with CPPD (P<0.01). Of those with CPPD deposits 40% required surgery at the end of the observation period, compared to 27.2% of those without deposits (P = 0.27). The waiting period before knee surgery was shorter in the OA + CPPD group but the difference was not statistically significant. In conclusion, local CPPD crystal deposition was observed in 25% of cases during the evolution of knee OA. No predictive factors were found. OA of the knee could, per se, favour the development of CPPD deposits. The occurrence of intra-articular CPPD deposits seemed to be related to a more rapid and severe evolution of OA of the knee. PMID- 11771529 TI - Eosinophilia as a side-effect of methotrexate in patients with chronic arthritis. AB - This report describes isolated reversible eosinophilia without additional subjective symptoms or signs in three patients on methotrexate therapy, two of them with juvenile idiopathic arthritis and one with rheumatoid arthritis. PMID- 11771530 TI - Spondylodiscitis due to Candida tropicalis as a cause of inflammatory back pain. AB - Spondylodiscitis may be either infectious or rheumatic in origin. In the latter case it may be seen more often in the context of spondyloarthropathies, giving rise to inflammatory back pain. We report the case of a man, affected by ulcerative colitis and carcinoma of the colon, who developed spondylodiscitis due to infection by Candida tropicalis. PMID- 11771531 TI - Amyopathic dermatomyositis associated with cervical cancer. AB - We here report a 44-year-old female patient who is the first documented case of cervical carcinoma with amyopathic dermatomysitis (ADM). The association of ADM with malignancy is clearly stated in the literature. This patient first presented with classic cutaneous findings of dermatomyositis with no signs and symptoms of muscle involvement for the first 7 months following the diagnosis. When this case has been worked up for malignancy by invasive procedures such as cervical cone biopsy, an increase in muscle enzymes and exacerbation of skin findings were detected. PMID- 11771532 TI - Anti-MPO-ANCA-positive microscopic polyangiitis following subacute bacterial endocarditis. AB - Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis. PMID- 11771533 TI - Osteoarticular brucellosis with long latent period. AB - We describe the case of a young male who manifested Brucella suis osteomyelitis after a 5-year period of relapsing monoarthritis. We discuss some of the difficulties regarding the diagnosis of osteoarticular brucellosis and review presentation patterns of the disease. PMID- 11771534 TI - Abdominal wall weakness and lumboabdominal pain revealing neuroborreliosis: a report of three cases. AB - The authors report three cases of thoracic radiculoneuropathy disclosing neuroborreliosis. All three patients had low back and abdominal pain and two had marked abdominal wall paresis. EMG confirmed a motor involvement of the lower thoracic roots and CSF analysis revealed a lymphocytic meningitis in all three cases. Antibodies against Borrelia burgdorferi were present in both the serum and the CSF. A favourable outcome was obtained in all three patients with appropriate antibiotherapy. The differential diagnosis of this misleading presentation is discussed. PMID- 11771535 TI - Iontophoretic evaluation of vascular reactivity to acetylcholine in patients with primary Raynaud's phenomenon and systemic sclerosis. PMID- 11771536 TI - Evaluation of renal function in patients with rheumatoid arthritis and amyloidosis. PMID- 11771537 TI - Simulation of the low-Earth-orbit dose rates using secondary radiations from the HZE particles at NIRS-HIMAC. AB - In order to study biological effects from cyclic dose rates encountered at the low-Earth orbit (LEO), an experimental facility was designed in the Biology room of the Heavy Ion Medical Accelerator in Chiba (NIRS-HIMAC). An incubator placed in this facility is irradiated repeatedly by secondary radiations from HZE particle beams supplied for independent users. The daily-average dose rate (1.4 mGy d-1) measured for 223 days and short-term dose rates measured for selected beam conditions were comparable to the dose rates observed in past LEO missions. Severe solar particle events can be simulated with hourly maximum dose rate of 2.8 mGy h-1. Preliminary measurements using CR-39 and TLD indicated that the dominant LET range is less than 5 keV micrometers-1. These results demonstrate the possibility of this facility for radiobiology studies of the effects of low dose rates comparable to the LEO environment. PMID- 11771538 TI - The integrating ion imager: a device for determining heavy ion doses during irradiations. AB - We have designed and built an integrating ion imaging system (I3) that records the spatial distribution of the dose of heavy ions incident on samples irradiated at the radiobiology beamline of the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The images of dose are integrated over the duration of the exposure. Unlike the images formed on X-ray film, these images are linear with the incident dose. Heavy ions are incident on a phosphor that is located just behind the sample position. Visible light emitted from the phosphor is collected by a lens and focused onto a scientific grade charge coupled device (CCD) cooled to about -45 degrees C. The phosphor and CCD camera are integral parts of a modular sample holder designed for irradiating molecular samples, which is easily mounted on the sample platform of the beamline. The imager can be adapted to other types of samples. The present CCD image is digitized to 14 bits (16,384 intensity levels), but the dynamic range is extended by adjusting the aperture of the CCD camera lens. Digital images from the CCD are routinely transferred over the BNL local area network for archival storage on a UNIX server, from which they can be opened from any authorized computer with access to the Internet. Images obtained with no sample in place record the dose at all points on the target field. When a sample is in place, an image of the sample appears providing its exact location with respect to fiducial marks recorded for all images. Areas surrounding the image of the sample are used in comparison with companion no-sample images to get exact doses over the sample. The contrast mechanism responsible for image formation is the shift along the Bragg curve resulting from loss of energy of the ions as they pass through the sample--not from a change in ion flux reaching the phosphor. The sharpness of the images formed with the DNA samples we have recorded indicates that neither scattering of the incident heavy ions or the generation of secondary ions contribute significantly. PMID- 11771539 TI - Cell inactivation by beryllium, boron and carbon ions at the low-energy irradiation facility of the Naples University. AB - The 3MV HVEC TTT-3 Tandem accelerator at the University of Naples, already used for radiobiological studies with protons and alpha particles, was set up for irradiation of biological samples with low energy carbon, boron, and beryllium beams. Radiobiological characterisation and study of these ion beams is essential in hadrontherapy (correction of hadrotherapy) to understand, for example, the possible biological effect of the target fragmentation products. Furthermore in space radiation biology we need to know the biological effects of heavy ions, a component of cosmic radiation that can contribute to the radiobiological risk when long sojourns in space are concerned. V79 Chinese hamster cells were irradiated with the different ions and the resulting cell inactivation data are reported. PMID- 11771540 TI - Dosimetry of low-energy protons on the vertical-beam facility at the Munich accelerator. AB - Various methods of dosimetry for protons with energies up to 25 MeV were compared for radiation fields as might be used in the skin treatment of patients or in biological experiments. The methods used were: Fluence of individually registered protons; Charge deposition in commercially available ionisation chambers; Thermoluminescence detectors, exposed in Munich and evaluated in Krakow; Photometricallly evaluated commercial Fricke dosimeter. An overall agreement within 5% was found between the absolute dose measurements. Depth-dose distributions for Bragg curves measured by a Markus chamber with a depth resolution of 10 micrometers agreed with calculations. PMID- 11771541 TI - 3-D confocal microscopy of etched nuclear tracks in CR-39. AB - Solid State Nuclear Track Detectors (SSNTD's) are used in a wide range of applications such as Geological Dating, Environmental Sciences (radon), life Sciences (Radiobiology, Dosimetry...), as well as Nuclear and Astro-Physics. In order to be observable under a microscope, the nanometric latent damaged trails due to the slowing down of charged particles into the SSNTD have to be specifically etched. In our laboratory, we are studying this chemical action and propose models that enable simulations to be performed. In the literature, the basic model uses two distinct etch-rates that are considered constant, VB; the Bulk and VT the Track etch-rate. A little bit more sophisticated and realistic, a model with a variable track etch-rate was established, taking into account the variation of energy deposition along the particle's trajectory. Up to now, the known methods used for determining the response function of CR-39 are very time consuming and strenuous. The method we present here is based on the use of the confocal microscope, which provides three-dimensional track images. The obtained set of 3-D co-ordinates can be treated mathematically, giving, in the framework of the two etch-velocity model, the response function. With this new approach, tracks are analysed one by one; response functions are obtained for each track and can be compared to fundamental characteristics of the charged Particle-Matter interactions. Moreover, the method we propose is applied semi-automatically and could easily be automated in the near future. PMID- 11771542 TI - RBE of radiations in space and the implications for space travel. AB - Space travellers are irradiated with cosmic rays to a dose rate considerably higher than that received on earth. In order to make sensible judgements about space exploration, the risks to health of such radiation need to be assessed. Part of the assessment of risk is to allow for the enhanced biological effectiveness of high LET radiations with respect to others. In space the high LET radiations of concern are high energy neutrons and charged particles. At the doses and dose rates encountered in space, the important risk is the induction of cancer in the astronauts. For this biological end-point there is no direct human evidence for the relative effectiveness of these radiations. There are some data for neutrons for cancer and life-shortening in laboratory animals but these are for fission spectra neutrons, which are of lower energy than those encountered in space. There is a small amount of data for protons and high energy heavier charged particles. The remaining evidence comes from cellular experiments observing chromosome aberrations and gene mutations. From this sparse information, pragmatic choices need to be made for application to protection in space. The data are reviewed and the bases for the pragmatic choices discussed. PMID- 11771543 TI - Monte Carlo predictions of DNA fragment-size distributions for large sizes after HZE particle irradiation. AB - DSBs (double-strand breaks) produced by densely ionizing space radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. DSB clustering at large scales, from >100 Mbp down to approximately 2 kbp, is modeled using a Monte-Carlo algorithm. A random-walk model of chromatin is combined with a track model, that predicts the radial distribution of energy from an ion, and the RLC (randomly-located-clusters) formalism, in software called DNAbreak. This model generalizes the random-breakage model, whose broken stick fragment-size distribution is applicable to low-LET radiation. DSB induction due to track interaction with the DNA volume depends on the radiation quality parameter Q. This dose-independent parameter depends only weakly on LET. Multi-track, high-dose effects depend on the cluster intensity parameter lambda, proportional to fluence as defined by the RLC formalism. After lambda is determined by a numerical experiment, the model reduces to one adjustable parameter Q. The best numerical fits to the experimental data, determining Q, are obtained. The knowledge of lambda and Q allows us to give biophysically based extrapolations of high-dose DNA fragment-size data to low doses or to high LETs. PMID- 11771544 TI - The role of promotion in carcinogenesis from protracted high-LET exposure. AB - Recent analysis of epidemiological studies using the two-stage clonal expansion (TSCE) model has shown that radiation-induced promotion dominates radiation induced initiation for protracted exposures to radon. This strong promotion effect (i.e. enhanced proliferation of already-initiated cells) causes a pronounced 'inverse dose-rate effect', but by a mechanism completely different from those usually discussed in this connection. This rather startling result is discussed along with implications to extended space missions that include a significant amount of high-LET radiation. It is suggested that the effect might be caused by a 'Bystander Effect' by which normal cells in the vicinity of initiated cells are hit by alpha particles and send out signals that modify the cell kinetics of the already-initiated clones. PMID- 11771545 TI - Mathematical models of radiation-induced mitotic delay: time course analysis and statistics of lesions. AB - Detailed investigations of high and low LET radiation induced chromosome aberrations in various mammalian cell lines have shown that the registered yield of aberrations depends on cell cycle progression delays. The effect of radiation on the cell kinetics can be analyzed in terms of kinetic growth models. The method yields the number of aberrant cells and the number of aberrations as totals obtained after integration over given time-interval. PMID- 11771546 TI - Ion-kill dosimetry. AB - Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'. PMID- 11771547 TI - Probability of hippocampus cell hits by high-LET space radiation in a low-Earth orbit mission (STS-91). AB - High-LET particles (HLP) of space radiation in the brain were measured with plastic nuclear track detectors (PNTD) using a life-size human phantom in the 9th Shuttle-Mir Mission (STS-91). Relationship between PNTD track-formation sensitivity (S) and LET infinity H2O was examined using heavy-ion beams at NIRS HIMAC. Average fluence of the HLP (HLP10) with LET infinity H2O greater than 10 keV micrometers-1 was evaluated as 1.3 x 10(4) n cm-2 for the 9.8-day low-Earth orbit mission (400 km x 51.65 degrees). Based on a simple extrapolation of these data, probability of HLP10 hits to hippocampus cells and cell-nuclei were estimated to be 45% and 7.0%, respectively, in a 90-day ISS mission. For 1 year, 91% of cells and 25% of cell-nuclei will be hit by HLP10. PMID- 11771548 TI - Inactivation of individual cells by divers ions at different LET values. AB - A new formula linking the shape of survival curve to the inactivation probabilities after different numbers of cell hits has been derived. It has been used in analyzing recent experimental data obtained with monolayer cells irradiated at definite values of LET (in different parts of Bragg peaks). The new approach allows not only deriving the values of inactivation probabilities at given LET values; unexpected consequences seem to follow especially for inactivation characteristics of carbon ions in different parts of the Bragg peak, too. PMID- 11771549 TI - Radiation-induced biological effects on crew members: a combined analysis on atmospheric flight personnel. AB - Human data on low dose rate radiation exposure and its effects are not readily available. A huge amount of such data may be obtained through flight personnel cohorts, in the form of epidemiological studies on delayed health effects induced by the cosmic-ray generated atmospheric ionizing radiation, to which flight personnel are exposed all throughout their work activity. All the available results from different studies on flight personnel exposure have been combined in various ways to evaluate the association between atmospheric ionizing radiation environment and health risks and to assess directions for future investigations. PMID- 11771550 TI - A Monte Carlo model for cell-cycle kinetics in charged particle irradiation. AB - In this paper we present a simulation of cell survival in Hadrontherapy. The work based on the Scholz-Kraft model extends the original approach to account both for the cell dimensions and radiosensitivity as a function of the time along the cell cycle. PMID- 11771552 TI - A model of radiation-induced myelopoiesis in space. AB - Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space. PMID- 11771551 TI - Modeling of radiation action based on nanodosimetric event spectra. AB - Assuming that the number of ionizations events within short segments of DNA-size volumes is a major factor of the biological effectiveness of ionizing radiation, we have designed and manufactured a new nanodosimetric detector counting ionization events in small wall-less gas volumes, which simulate such DNA segments. The detector measures individual ionizations in low-pressure (~1 Torr) propane or any other gas corresponding to a tissue-equivalent cylindrical volume of 2-4 nm diameter and up to 30 nm length. While first nanodosimetric event spectra with protons and alpha particles are being obtained, it is important to develop and test a theory that relates these spectra to biological endpoints such as strand breakage, mutations, and lethal cellular events. This paper describes the two-compartment theory, which is based on the premise that energy deposition in nanometer sites can be broadly divided into two categories: a low-energy deposition compartment comprising events with a total number of 2-5 ionizations, and a high-energy deposition compartment comprising events containing 6-10 ionizations. Under standard biochemical conditions, these events will lead to different biological consequences. The fate of DNA lesions produced by low-energy deposition events will mostly depend on the repair capacity of the irradiated cells, whereas events produced by high-energy deposition events will be irreparable. These events are therefore the biologically most relevant lesions, since they inevitably lead to mutation and cell death. PMID- 11771553 TI - [Repraeputiatio glandis. Operations on circumcised men. Historical outline and technique]. AB - Historical outline of circumcision and its meaning for numerous societies. Circumcision is a very characteristic mark, especially for the confessors of Judaism. Nevertheless, it is known from the world history that during persecution periods it used to be a hidden seal. So, circumcision has been always accompanied by reconstruction operations, which had been known even in the ancient Rome. A number of such operations and attempts of reconstruction of prepuce grew considerably during the 2nd World War. The author presents his own operation materials and observations. PMID- 11771554 TI - [Doctor's degree thesis of Tomasz Adolf Wolkowinski "Carditidis rheumaticae historia"]. AB - In 1817 on the University of Vilnius Faculty of Medicine, T. A. Wolkowinski, a student of the eminent clinician Jozef Frank, defended his doctor's degree thesis about a direct relation between rheumatic disease and cardiomegaly. It was probably the first paper in Poland describing with details the rheumatic heart disease. Unfortunately we don't know much about T. A. Wolkowinski's life. PMID- 11771555 TI - [Medical institutions and physicians in the district of Garwolin during the period the II Republic of Poland]. AB - Presentation of the District Hospital in Garwolin and the Regional Council Hospital in Maciejowice. List of names of physicians working in hospitals, public health centers and sick-fund centers. Biographies of physicians proceeding from the district and related somehow with it during the period of the II Republic, namely: Feliks Malinowski, Czeslow Bogucki, Jozef Kenig, Stefan Nizinski, Stefan Soszka, Wladyslaw Galasinski, Jozef Mazurek. PMID- 11771556 TI - [Interuniversity Medical Library in Paris (BIUM) Collection of the Polish theses for doctor degrees]. AB - The study consist of two parts. The first refers to the history and the present of Medical Library in Paris - one of the richest European medical book libraries, containing among others collection gathered by Medical Faculty and the Royal Medical Society since 1391. An abridged description of its edifice in the University of Rene Descartes, interior decorations of its main hall and opened quarters, as well as exhibits of the Museum of Medicine History is given. Author rises merits of professor Pierre Sue - surgeon and librarian - rendered by rescue of the library dismembered during the revolution of 1789. Here we shall find references of the most valuable incunabula and rare prints of the collection, distinctive for particular periods of progress in medicine and printing art. The second part of study contains information about unique collection of doctor theses presented in Medical Faculty since 1539 to 1778, and dissertations from Montpellier, Strasbourg and universities abroad - up to 1778. Particularly important seem to be titles of 32 theses prepared by the Polish authors awarding doctor degrees in Paris in the years 1890-1900 retrieved by the author, as completing in this field the Stanislas Konopka's Polish Medical Bibliography of XIX century (vol. IX, article: Doctor Theses - Paris). PMID- 11771557 TI - [Contribution to fight against cholera in an instance of epidemic in Osieciny, Eastern Kujawy in 1852]. AB - Description of activities of Lieutenant-Colonel Tomasz Zielinski who was not a physician, but being an officer of the Russian army during the Turkish campaign in 1831, had acquainted himself with methods of fighting against cholera and he used them with quite a good result in Osieciny in 1852. PMID- 11771558 TI - Joint remedies. AB - Glucosamine and chondroitin supplements appear to ease arthritis symptoms and possibly fight the disease itself. We tested 19 national products. PMID- 11771559 TI - Take two aspirins and e-mail me in the morning. AB - E-mailing your doctor has potential benefits. But there are pitfalls. PMID- 11771560 TI - Innovative treatments for irritable bowel syndrome featured in new continuing ed program. PMID- 11771561 TI - Combination therapy may improve treatment of heart attack patients. PMID- 11771562 TI - Health system-jail partnership improves community health outcomes. PMID- 11771563 TI - Initiative raises use of interventions that prevent second heart attacks. PMID- 11771564 TI - Consensus guidelines offer more effective management of Helicobacter pylori related disease. PMID- 11771565 TI - Results of 12-year study show brachytherapy is as effective as surgery. PMID- 11771566 TI - Stroke initiative speeds time of tPA administration. PMID- 11771567 TI - New public health service guideline calls on health professionals to make treating tobacco dependence a top priority. PMID- 11771568 TI - Lower death rate among patients when recovery supervised by anesthesiologist. PMID- 11771569 TI - Overview on clinical data of dexibuprofen. AB - Several clinical trials, post-marketing surveillance studies and a meta-analysis were performed to obtain information about dose finding, pharmacokinetics, special indications, tolerability and compliance. In eight clinical trials, according to GCP, 1463 patients were included. Six of the trials were double blind studies against placebo, racemic ibuprofen and diclofenac; the pharmacokinetic study and a long-term safety study were open studies. A meta analysis of five clinical trials compared tolerability and safety data between dexibuprofen and racemic ibuprofen. Three PMS studies collected data on 7133 outpatients. All clinical trials and PMS studies have been published. In the dosage ratio 0.5:1, dexibuprofen was found to be at least as efficacious as racemic ibuprofen; 75% of the maximum daily dose of dexibuprofen was equally efficacious as 100% of MDD of diclofenac; no influence was found of meals on bioavailability and a significant doseresponse relationship; there was clinical efficacy in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis of the hip, osteoarthritis of the knee, lumbar vertebral syndrome, distortion of the ankle joint and dysmenorrhoea; there was good tolerability compared to other NSAIDs: racemic ibuprofen showed a 30% and diclofenac a 90% higher incidence of adverse drug reactions; the long-term study stated a 15.2% adverse drug event incidence; the incidence of adverse drug reactions in the PMS studies was between 5.5% and 7.4%, and withdrawals were between 2.3% and 2.7%. In conclusion, dexibuprofen (Seractil) has the stature of a modern NSAID, combining the high efficacy of diclofenac with the good tolerability of ibuprofen, and need not hide behind the new generation of COX-2 inhibitors. PMID- 11771570 TI - Treatment of non-malignant pain in the Dutch GP population: an analysis of treatment standards, prescription habits and basic attitudes. AB - The aim of this study was to evaluate whether dexibuprofen meets the basic requirements of Dutch General Practitioners (GPs) for acceptance as an analgesic in mild to moderate pain. The available GP treatment standards for mild to moderate pain were analysed. If no treatment standard was available, results from two semistructured round table group sessions were used. The available treatment standards are either diagnosis oriented (e.g. otitis media) or symptom oriented (e.g. lower backache). Prescription data (1988-2000) show that GPs usually prescribe the medication suggested by the standards. Paracetamol, diclofenac, ibuprofen and naproxen, all over 25 years old, have a combined marketshare greater than 84%. Most new drugs have been short-lived and/or little prescribed. Round tables show three basic dimensions to pain treatment: objective, subjective, and the action taken to relieve the pain. The objective dimension relates to anamnesis and physical examination to rule out serious causes. The subjective dimension relates to the doctor's assessment of the pain threshold of the patient, expectations towards the doctor, and previous action taken by the patient. The pain relief dimension relates to acceptance of the pain by the patient, the solution proposed by the doctor and the way this is presented. Medication prescribed should be exclusive for doctors. The GP must also have faith in the medication, and so previous experience is a dominant factor in the choice made. GPs are relatively insensitive to new products, as there are few unmet needs. As a new NSAID dexibuprofen meets two basic requirements. First, it is only available to doctors. Secondly, because it is a pure form of ibuprofen, doctors can relate to extensive previous experience when prescribing it. This might ensure its rapid acceptance compared to other new NSAIDs. PMID- 11771571 TI - Efficacy and long-term safety of dexibuprofen [S(+)-ibuprofen]: a short-term efficacy study in patients with osteoarthritis of the hip and a 1-year tolerability study in patients with rheumatic disorders. AB - The efficacy study was performed to prove the equivalent efficacy of dexibuprofen compared to the double dose of racemic ibuprofen and to show a clinical dose response relationship of dexibuprofen. The 1-year tolerability study was carried out to investigate the tolerability of dexibuprofen. In the efficacy study 178 inpatients with osteoarthritis of the hip were assigned to 600 or 1200 mg of dexibuprofen or 2400 mg of racemic ibuprofen daily. The primary end-point was the improvement of the WOMAC OA index. A 1-year open tolerability study included 223 outpatients pooled from six studies. The main parameter was the incidence of clinical adverse events. In the efficacy study the evaluation of the improvement of the WOMAC OA index showed equivalence of dexibuprofen 400 mg t.i.d. compared to racemic ibuprofen 800 mg t.i.d., with dexibuprofen being borderline superior (P = 0.055). The comparison between the 400 mg t.i.d. and 200 mg t.i.d. doses confirmed a significant superior efficacy of dexibuprofen 400 mg (P = 0.023). In the tolerability study the overall incidence of clinical adverse events was 15.2% (GI tract 11.7%, CNS 1.3%, skin 1.3%, others 0.9%). The active enantiomer dexibuprofen proved to be an effective NSAID with a significant dose-response relationship. Compared to the double dose of racemic ibuprofen, dexibuprofen was at least equally efficient, with borderline superiority over dexibuprofen (P = 0.055). The tolerability study in 223 patients on dexibuprofen showed an incidence of clinical adverse events of 15.2% after 12 months. The results of the studies suggest that dexibuprofen is an effective NSAID with good tolerability. PMID- 11771572 TI - Pain treatment with NSAIDs, primary focus on ibuprofen. AB - For the past 30 years ibuprofen has been known as one of the safest NSAIDs and in some countries, including The Netherlands, it is available as an over-the-counter medicine. Nevertheless, all NSAIDS may show adverse effects, such as gastrointestinal toxicity, sodium/water retention, reduced kidney perfusion and allergic responses. In developing safer NSAIDs two new types of drug have been introduced: the COX-2 inhibitors and the single enantiomer NSAIDs, in particular S(+)-ibuprofen. S(+) ibuprofen shows an equipotency with half of the racemic ibuprofen dose , and the introduction of S(+) ibuprofen (dexibuprofen, Seractil) permits the prescription of lower doses. The new COX-2 inhibitors have recently been compared to the racemic ibuprofen. Day et al. found no significant difference between rofecoxib and racemic ibuprofen concerning overall incidence rates of clinical adverse experiences. In the study by Silverstein et al. the annualised incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs ibuprofen showed no statistical difference (P = 0.09), but for patients not taking aspirin, a difference was found in favour of celecoxib (P = 0.04). Studies comparing the COX-2 inhibitors and dexibuprofen need to be performed. PMID- 11771573 TI - Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen. AB - Racemic ibuprofen, which contains equal quantities of R(-)-ibuprofen and S(+) ibuprofen, has been used as an anti-inflammatory and analgesic agent for over 30 years. Although the S(+)-enantiomer is capable of inhibiting cyclooxygenase (COX) at clinically relevant concentrations, R(-)-ibuprofen is not a COX inhibitor. The two enantiomers of ibuprofen are therefore different in terms of their pharmacological properties and may be regarded as two different 'drugs'. They also differ in terms of their metabolic profiles. For example, R(-)-ibuprofen becomes involved in pathways of lipid metabolism and is incorporated into triglycerides along with endogenous fatty acids. S(+)-Ibuprofen does not appear to become involved in these unusual metabolic reactions, which is why S(+) ibuprofen is regarded as being metabolically 'cleaner' than racemic ibuprofen. When racemic ibuprofen is given to humans, a substantial fraction of the dose of R(-)-ibuprofen (50%-60%) undergoes 'metabolic inversion' to yield S(+)-ibuprofen. On this basis, it has been argued that to obtain clinical effects that are comparable to those of a given dose of racemic ibuprofen, the dose of S(+) ibuprofen would need to be about 75% of the dose of the racemate. However, this 'pharmacokinetic' rationale does not take into account the fact that inversion is not instantaneous, that there is variability in the extent of inversion between individuals, and that the kinetics of inversion may differ depending on the dosing situations. For example, the extent of inversion appears to be reduced when the racemate is given to patients experiencing acute pain. Recent studies have demonstrated that the clinical benefits of racemic ibuprofen can be derived from the administration of the single S(+)-enantiomer at a dose that is half that of the racemate. For example, 200 mg of S(+)-ibuprofen has been found to be superior or at least equivalent to 400 mg of the racemate in the relief of dental pain. Possible explanations for this higher than expected efficacy of S(+) ibuprofen are considered. PMID- 11771574 TI - In vitro evaluation of the antimicrobial activity of a castor oil-based irrigant. AB - The antimicrobial activity of irrigating solutions--Endoquil (castor oil detergent), 2% chlorhexidine gluconate solution, and 0.5% NaOCl solution-was evaluated against gram-positive cocci (Micrococcus luteus, Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus mutans, and Streptococcus sobrinus), gram-negative rods (Escherichia coli and Pseudomonas aeruginosa), and the yeast Candida albicans. Activity was evaluated using the two layer agar diffusion technique. The base layer was obtained by pouring 10.0 ml of Muller Hinton Medium or 10.0 ml of Brain Heart Infusion agar in a Petri dish. After solidification a 5.0 ml seed layer of Muller Hinton Medium or Brain Heart Infusion agar with inoculum (106/ml) was added. Absorbent paper disks (6.0 mm in diameter) immersed in the solutions were placed at equidistant points. Plates were maintained at room temperature for 2 h for prediffusion of the solutions and incubated at 37 degrees C for 24 h. The candle jar system was used for the Brain Heart Infusion agar plates. All tests were performed in duplicate. After incubation the medium was optimized with 0.05 g% triphenyltetrazolium chlorate gel and inhibition halos were measured. All bacterial strains were inhibited by 2.0% chlorhexidine gluconate. Endoquil was effective against gram-positive microorganisms, and 0.5% NaOCl was effective only against S. aureus. PMID- 11771575 TI - Two methods to evaluate the antimicrobial action of calcium hydroxide paste. AB - The objective of this study was to analyze two methods for determining the antimicrobial effectiveness of (i) calcium hydroxide plus saline, (ii) calcium hydroxide plus polyethylene glycol, and (iii) calcium hydroxide plus camphorated paramonochlorophenol. Four microorganisms (Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), and Bacillus subtilis (ATCC 6633)), one yeast (Candida albicans (ICB/USP-562)), and one mixture of these organisms were used. The strains were inoculated in Brain Heart Infusion (BHI) and incubated at 37 degrees C for 24 h. Two methods, the direct exposure test and the agar diffusion test were used to evaluate antimicrobial effects. For the direct exposure test (DET) 288 paper points were contaminated with the standard microbial suspensions and exposed to the intracanal dressings for 1, 24, 48, and 72 h. The points were immersed in Letheen Broth, followed by incubation at 37 degrees C for 48 h. An inoculum of 0.1 ml obtained from Letheen Broth was then transferred to 7 ml of BHI under identical incubation conditions, and microbial growth was evaluated. Pastes showed activity between 1 and 72 h, depending on the microorganism/mixture tested. For the agar diffusion test 36 Petri plates with 20 ml of BHI agar were inoculated with 0.1 ml of the same microbial suspension used for the DET, using sterile swabs that were spread on the medium. Five cavities were made in each of two agar plates (total = 10) and completely filled with one of the calcium hydroxide pastes. The plates were preincubated for 1 h at environmental temperature and then incubated at 37 degrees C for 24 to 48 h. The inhibition zone around each well was recorded in millimeters, and the results were submitted to ANOVA and Tukey test (alpha = 0.05). All intracanal dressings induced inhibition zones (range 5.0-10.0 mm). Data obtained showed that both the DET and agar diffusion test are useful in establishing the calcium hydroxide antimicrobial spectrum, thus improving infection control protocols. The direct exposure method is independent of other variables and is a practical laboratory procedure. A complete antimicrobial effect was observed after 48 h on indicator microorganisms, in both tests, irrespective of the calcium hydroxide paste vehicle. PMID- 11771576 TI - Effect of repeated vertical loads on microleakage of IRM and calcium sulfate based temporary fillings. AB - Temporary fillings are commonly used to seal endodontic access cavities between visits. IRM and Cavidentin were selected to represent two widely used groups of temporary filling materials. The first is a reinforced zinc oxide-eugenol preparation that is mixed at chairside, whereas the second is a ready-to-use calcium sulfate-based material that gained popularity due to its convenience of application. The seal provided by the aforementioned materials was studied using a radioactive tracer quantitative assay. When compared as passive temporary filling, the two provided a similar quality of seal. However, when subjected to repetitive "occlusal" cyclic loading of 4 kg, IRM was clearly superior to the calcium sulfate-based material. Whereas IRM maintained a reasonable seal, the calcium sulfate-based fillings deteriorated and lost the ability to seal. These results suggest that even though calcium sulfate-based materials may be useful when not subjected to any occlusal forces, IRM should be preferred whenever occlusal loads may be applied. Furthermore it is demonstrated that testing such materials for microleakage with no reference to mastication forces may be of limited value. PMID- 11771577 TI - Antibacterial activity of fifth-generation dentin bonding systems. AB - Past concepts that the pulp does not become infected until an actual carious exposure takes place have been challenged. The antibacterial effects of the dentin bonding systems Single Bond, Prime&Bond NT, and Excite were evaluated using the bacteria Streptococcus mutans ATCC 25175, Streptococcus intermedius, Lactobacillus acidophilus, Prevotella oris, Prevotella bivia, Prevotella denticola, Porphyromonas gingivalis, Porphyromonas endodontalis, and Clostridium ramosum with a disk diffusion method. Chlorhexidine (0.2%) was used as a positive control. After incubation zones of inhibited bacterial growth were measured. Prime&Bond NT showed growth inhibition for all bacterial strains. Lactobacillus acidophilus and Streptococcus mutans were remarkably resistant to Single Bond, whereas EX produced no inhibitory effect on Porphyromonas endodontalis, although the adhesive produced the maximum halo inhibition to Streptococcus mutans (15+/-1 mm), showing an antibacterial effect closest to chlorhexidine. The variety of results obtained in this study suggest that antibacterial properties of current dentin adhesives may depend on components that are originally incorporated to promote adhesion. PMID- 11771578 TI - Effect on the healing of periapical perforations in dogs of the addition of growth factors to calcium hydroxide. AB - The purpose of this study was to investigate the effect of the addition of platelet-derived growth factor-BB and insulin-like growth factor-I to calcium hydroxide in the repair of apical perforations in dogs. Fifty-one premolar teeth of four beagle dogs were used. After developing periapical lesions root apices were artificially perforated. The teeth were divided into the three groups: group 1, the apical perforations were not sealed; group 2, the perforated areas were obturated with calcium hydroxide; and group 3, calcium hydroxide plus growth factors was applied to the sites of perforation. All canals were filled by a lateral condensation technique. Animals were killed 12 wk later, and sections were hematoxylin & eosin-stained and immunostained for osteonectin. The amount of inflammation was evaluated histomorphologically. The one-way ANOVA test demonstrated that the three groups were significantly different from one another. In group 3 there was no inflammatory reaction of apical tissue, and the connective tissue adjacent to the newly formed hard tissue was strongly immunostained for osteonectin. Most sections in group 1 showed no apical healing. Moderate healing was found in group 2. In conclusion the combination of platelet derived growth factor-BB and insulin-like growth factor-I with calcium hydroxide improved healing of apical perforation in dogs. PMID- 11771579 TI - Tetracycline HCl solution as a root canal irrigant. AB - The effect of tetracycline hydrochloride as an endodontic irrigant on smear layer removal was examined by scanning electron microscopy and compared with bidistilled water, 2.5% sodium hypochlorite (NaOCl), and 50% citric acid in 20 extracted teeth. Five teeth, as a control, were irrigated with bidistilled water only in group 1. All the other groups were irrigated with NaOCI during instrumentation. The final rinses were NaOCl in group 2, citric acid in group 3, and 1% tetracycline hydrochloride in group 4. Scanning electron microscopic results and statistical analysis revealed that bidistilled water and NaOCl were ineffective in removing the smear layer, whereas citric acid and tetracycline hydrochloride were significantly more effective (p < 0.001). No statistically significant difference was detected between tetracycline hydrochloride and citric acid (p > 0.05). However tetracycline hydrochloride demineralized less peritubular dentin. PMID- 11771580 TI - Cytotoxic effects of 10% citric acid and EDTA-T used as root canal irrigants: an in vitro analysis. AB - EDTA-T and 10% citric acid used as root canal irrigants lead to more visible dentinal tubules than 5% sodium hypochlorite associated with 3% hydrogen peroxide. However, these cleansing agents must be compatible with apical periodontal tissue. We analyzed the cytotoxicity of 10% citric acid and EDTA-T in cultured fibroblasts using Trypan blue. The solutions were diluted to 1%, 0.1%, and 0.01% and applied to NIH 3T3 cell cultures. Cells grown on fresh DMEM served as a control. After 0, 6, 12, and 24 h (short-term assay, viability) and 1, 3, 5, and 7 days (long-term assay, survival), the cells were counted using a hemocytometer. In short-term tests, cell viability ranged from 85% to 99% for all experimental groups with no statistical differences when compared with control cultures, except for the group treated with 1% EDTA-T, which caused a progressive decrease in cell viability. In long-term tests, all cultures increased in number from day 1 to the end of the experimental period, showing no inhibition of cell proliferation, except for the cultures treated with 1% EDTA-T, which totally prevented cell growth. All dilutions of 10% citric acid were more biocompatible than EDTA-T. Cultures treated with citric acid had a higher percentage of viable cells in the short-term assays, and the cells retained their self-renewal capacity. PMID- 11771581 TI - Evaluation of the genotoxicity of zinc oxide eugenol-based, calcium hydroxide based, and epoxy resin-based root canal sealers by comet assay. AB - Three main types of root canal sealer are currently commonly used in pulp treatment: zinc oxide eugenol-based, calcium hydroxide-based, and epoxy resin based sealers. In the present study, the genotoxicity of sealer on oral carcinoma cells was evaluated by single-cell gel electrophoresis assay (comet assay). The whole length of the comet and the diameter of the head were measured using an image analysis system. The results were analyzed by one-way analysis of variance to compare the various means. The zinc oxide eugenol-based sealers (Canals, Canals-N, and Tubilseal) did not always cause a dose-dependent increase in genotoxicity. The resin-based sealers (Topseal, AH 26, and AH Plus) caused a dose dependent increase in genotoxicity, but no such effect was seen with the calcium hydroxide-based sealer (Sealapex). The highest level of DNA damage was induced by the resin-based sealers. PMID- 11771582 TI - Production of interleukin-8 and nitric oxide in human periapical lesions. AB - Bacterial infection of the pulp and root canal system leads to the recruitment of immunocompetent cells in the periapex and stimulates inflammatory cell responses to produce a variety of inflammatory mediators. Cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates are frequently found at sites of acute inflammation. In this study, we measured the levels of interleukin (IL) 8 and nitric oxide (NO) in the periapical exudate (PE) from human periapical lesions and investigated the association of these mediators with the clinical symptoms of periapical periodontitis. PE samples were collected from root canals during routine endodontic treatments. The IL-8 concentration was measured by the enzyme-linked immunosorbent assay, and the NO level was measured as nitrite/nitrate concentration assayed by the Griess reaction. Detectable levels of IL-8 and nitrite/nitrate were found in 24 and 19 of 27 PE-samples, respectively. Although PE-IL-8 and nitrite/nitrate concentration showed a broad range, a significantly positive correlation was found between both mediators. Also, significantly higher IL-8 levels were found in PE from lesions that had painful symptoms at the sampling visit. However, there was no relationship between elevated NO levels and clinical symptoms. These results suggest that the up-regulation of IL-8 may have a critical role in the development of the symptoms of periapical disease. PMID- 11771583 TI - Effects of sodium hypochlorite and RC-prep on bond strengths of resin cement to endodontic surfaces. AB - There is concern that the use of sodium hypochlorite (NaOCl) and RC-Prep may lower the bond strength of resin cements. The objective of this study was to evaluate the effect of 5% NaOCl and RC-Prep treatment on the bond strength of a resin cement, C&B Metabond. Control roots (group 1) were biomechanically prepared using 0.9% NaCl as an irrigant; group 2, roots with 5% NaOCl; group 3, roots with RC-Prep; group 4, roots with 0.9% NaCl followed by 10% ascorbic acid; group 5, roots with 5% NaOCl followed by 10% ascorbic acid (pH 4); group 6, roots with 5% NaOCl followed by 10% neutral sodium ascorbate; and group 7, roots with RC-Prep followed by 10% ascorbic acid. All roots were then filled with C&B Metabond, incubated in water for 24 h, and then cross-sectioned into six 1-mm thick slabs representing cervical and middle root dentin. The slabs were trimmed and tested for tensile bond strength. The results demonstrated that both 5% NaOCl and RC Prep produced significantly (p < 0.05) large reductions in resin-dentin bond strengths, and the reductions could be completely reversed by the application of either 10% ascorbic acid or 10% sodium ascorbate. PMID- 11771584 TI - Three-point bending test of fiber posts. AB - Five different types of fiber posts (carbon fiber Composipost radio-opaque, quartz fiber Aestheti-Plus, carbon fiber Carbotech, glass fiber Light post, and silica fiber Snowpost) were submitted to a three-point bending test after being stored for 1 yr under three different conditions: dry storage at room temperature, storage in 37 degrees C water, and storage in bovine teeth that were endodontically treated and restored with composite resin. The posts were observed before and during the test by confocal microscopy. More voids were found within the Composipost radio-opaque than in other posts. Posts of all groups that were stored in water showed flexural strength values lower than posts that were stored dry. In all storage conditions, Carbotech posts showed higher flexural strength values than Composiposts and Snowposts, and Aestheti-Plus posts showed higher flexural strength values than Snowposts. Posts that were stored in bovine teeth showed flexural strength values similar to those of posts that were stored dry. It was concluded that fiber posts must not be in contact with oral fluids and that during the 1-yr storage in bovine teeth, they were sufficiently protected from this contact by the apical root canal filling and by the coronal composite resin filling. PMID- 11771585 TI - Comparison of distortion and separation utilizing profile and Pow-R nickel titanium rotary files. AB - The purpose of this study was to determine whether there was a difference in the frequency of file distortion and separation between nickel-titanium (Ni-Ti) ProFile 0.04 ISO taper rotary files and Ni-Ti Pow-R 0.04 ISO taper rotary files. For this study, 60 mesial root canals in 30 human mandibular first molars were chosen with the curvature angle of the mesiobuccal and mesiolingual canals of the same tooth within five degrees. ProFile and Pow-R files were randomly assigned to either the mesiobuccal or mesiolingual canal of the same tooth. Instrumentation proceeded per the manufacturer's recommendations, in a crown-down technique, using Gates Glidden burs and rotary files in sizes #50 to #20. Positive and negative controls were used. The instruments were evaluated for signs of distortion or separation by three independent evaluators using magnification under microscope. A total of 420 files were evaluated, 210 files for Pow-R and 210 files for ProFile. There was no statistically significant difference in the incidence of instrument distortion or separation between the two file systems that were studied. PMID- 11771586 TI - Antimicrobial activity of several calcium hydroxide preparations in root canal dentin. AB - The purpose of this study was to evaluate the antimicrobial activity of several calcium hydroxide (Ca(OH)2) preparations in root canal dentin infected with Enterococcus faecalis. Roots of extracted bovine incisors were prepared to standardized cylindrical test specimens of 5 mm in height; the smear layer was removed, and the specimens were incubated for 24 h at 37 degrees C in bacteriological culture medium that contained 7.0 x 10(4) colony forming units per milliliter of E. faecalis. The specimens were mounted in individual 4-mm diameter culture wells, and the test material was applied to fill the canal lumen. There were five treatment groups: group 1, a thick mixture of Ca(OH)2 USP (1.0 g/ml H2O); group 2, a thin mixture of Ca(OH)2 USP (0.1 g/ml H2O); group 3, Pulpdent TempCanal paste; group 4, sterile H2O (positive control); and group 5, 25 dentin specimens in sterile, uninoculated brain-heart infusion broth that were included as negative controls. Quantitative microbiological analysis of dentin at various depths was completed after 24 h. All groups showed a significant (p < 0.001) decrease in numbers of E. faecalis in all depths of dentin compared with the control. Groups 2 and 3 demonstrated significantly greater antimicrobial activity (73%-86% reduction) at all depths of dentin tested compared with group 1 (13%-26%) (p < 0.05). These results suggest that Ca(OH)2 can decrease the numbers of E. faecalis at all depths of dentinal tubules within 24 h and that thin preparations of Ca(OH)2 may be more effective in the elimination of E. faecalis from dentinal tubules than thick preparations. PMID- 11771587 TI - Post retention: the effect of sequence of post-space preparation, cementation time, and different sealers. AB - Many endodontic sealers contain constituents that have been shown to inhibit the polymerization of resin cements. This may be important when prefabricated posts are cemented at the same appointment as root canal obturation. This study evaluated the effects of cementing posts with a resin cement immediately or at a delayed time period after obturation using Roth's 801 Elite Grade or AH26 sealer cements. The contribution of mechanical post-space preparation was also assessed as a critical variable. One hundred twenty extracted canines were randomly divided into eight experimental groups. The variables evaluated were the order of post preparation (either before or after obturation), the type of sealer used, and the time of post cementation. All teeth received a stainless steel #6 Parapost XP cemented with a resin cement, Panavia 21. Each experimental group underwent tensile testing for retention using an Instron universal testing machine. For both sealers posts cemented in teeth in which the canal was obturated before post-space preparation and thus had sealer-contaminated dentin removed by the space preparation procedure had significantly higher retentive values than those obturated after post-space preparation in which contaminated dentin might remain. Sealer used and time of cementation had no specific effect on retention. Achieving a clean, "freshened" dentinal surface during mechanical post-space preparation seems to be a critical variable for post retention when a resin cement is used. PMID- 11771588 TI - Cyclic fatigue of nickel-titanium rotary instruments after clinical use with low- and high-torque endodontic motors. AB - This study investigated the cyclic fatigue resistance of used nickel-titanium rotary instruments, clinically operated by a traditional high-torque motor and a new low-torque electric motor. Fifty instruments (ProFile, Maillefer, Baillagues, Switzerland) for each of the following sizes were used: .06-25, .06-20, and .04 25. They were divided into three groups: A = 10 new instruments (control), B = 20 used instruments operated by a high-torque motor, and C = 20 used instruments operated by a low-torque motor. Each instrument was used in 10 clinical cases (at least six molars). Cyclic fatigue testing of new and used instruments was performed with a device that allowed the instruments to rotate freely inside a stainless-steel artificial canal at 350 rpm. Data were recorded and statistically analyzed. Mean (and SD) numbers of rotation-to-breakage cycles for .06-25, .06 20, and .04-25 instruments were, respectively: group A 463 (85), 535 (101), and 613 (105); group B 229 (64), 343 (92), and 233 (84); and group C 352 (77), 454 (89), and 466 (86). Results showed that group A instruments exhibited significantly higher values of rotation-to-breakage cycles (two-sample t test, p < 0.01), when compared with groups B and C, respectively. Statistically higher resistance to cyclic fatigue was noted for group C in all sizes compared with group B (two-sample t test, p < 0.01), showing that the use of endodontic motor with lower torque values reduced cyclic fatigue of nickel-titanium rotary instruments. PMID- 11771589 TI - Effects of chlorhexidine gluconate as an endodontic irrigant on the apical seal: short-term results. AB - The aim of this study was to ascertain whether chlorhexidine gluconate (0.12%), used as an endodontic irrigating solution would affect the apical seal obtained when using three different root canal cements. One hundred extracted human single canal teeth were divided into 9 experimental groups of 10 teeth each and a positive and negative group of 5 teeth each. The teeth were decoronated at the level of the cementoenamel junction, then accessed, instrumented to a Master Apical File #50, irrigated with either sterile saline, 5.25% NaOCl or 0.12% chlorhexidine gluconate, and dried using paper points. Obturation was accomplished using lateral condensation and 1 of 3 endodontic sealers: Roth's 811, AH26, or Sealapex. At 90 and 180 days after obturation apical leakage was measured using the fluid filtration method. Using the ANOVA test the results showed no significant difference in seal related to the irrigant at both the 90- and 180-day observation periods. PMID- 11771590 TI - Measurement of endodontic file lengths: calibrated versus uncalibrated digital images. AB - This in vitro study compared the accuracy of file length measurements made on calibrated and uncalibrated direct digital images. Endodontic files of known lengths and ISO sizes were used in 10 single-rooted, relatively straight teeth within cadaver specimens. The crowns of the teeth were ground flat and an orthodontic wire of known length was secured to the coronal surface. This wire was placed mesiodistally and perpendicular to the root and served as the reference point for the file measurement and as a calibration reference length. A #20 file was hand-measured to a length that reached the apical third of each tooth. It was inserted and a radiographic image was secured. The instrument was remeasured three additional times at different lengths on the same tooth and reinserted before each image acquisition. Thus 40 digital images were acquired using a GE X-ray unit and a Schick Computed Dental Radiography (CDR) #2 sensor. These images were placed in random order, and an independent, blinded investigator determined the file lengths using on-screen calibrated and uncalibrated measurement of the CDR image with a straight-line and multiple-line measuring technique. The experimental measurements were compared with each other and with the known clinical measurements. A two-way analysis of variance indicated that there was a statistically significant difference showing that the calibrated measurements were more accurate than the uncalibrated measurements (p = 0.0001), and there was no significant difference between the straight-line and multiple-line measuring techniques (p = 0.14). PMID- 11771591 TI - Defects in GT rotary instruments after use: an SEM study. AB - Used rotary nickel-titanium instruments require frequent replacement. This laboratory study evaluated defects of GT Rotary instruments before and after usage. The instruments were fixed into custom-made holders and photographed in an SEM at x 260 to x 12,000 magnification at preset points. Instrument sizes 20 with 1.0, 0.8, and 0.6 taper and instrument sizes 35 with 1.2 taper were used in 12 canals. The used instruments were cleaned and then reexamined in an SEM as before. The presence of 11 types of conditions was scored from the pre- and postusage photographs. No instruments fracturing or plastic deformation was observed during the test. The presence of debris, pitting, and scraping changed significantly. Imperfections were found on used GT Rotary instruments and the presence of defects (pitting, scraping, and blunt-cutting edges) increased in all of the instruments. The behavior of GT Rotary instruments with usage seems to be different, compared with that found in other instruments. PMID- 11771592 TI - Comparison of laterally condensed .06 and .02 tapered Gutta-Percha and sealer in vitro. AB - The purpose of this in vitro study was to compare the quality of the seal in canals prepared in a standardized manner and obturated with a .06 or a .02 tapered gutta-percha master cone using lateral condensation. Forty-four extracted human anterior teeth with single, straight canals were divided into two experimental groups of 20 teeth each and two control groups of 2 teeth each. The teeth were instrumented with Series 29 Profile .06 tapered rotary nickel-titanium files to a master apical file of 0.46 mm. Teeth in group 1 were obturated with a .02 tapered master gutta-percha cone and Roth 801 sealer using lateral condensation. Teeth in group 2 were obturated similarly, except a .06 tapered master gutta-percha cone was used. The depth of spreader penetration was recorded in millimeters. Positive control teeth were instrumented but not filled. Negative control teeth were instrumented, obturated, and externally sealed. The teeth were placed into a coronal leakage apparatus that contained an upper and lower reservoir of trypticase soy broth separated by the tooth. A 24-h growth of Proteus vulgaris in 0.25 ml of trypticase soy broth was placed in the coronal reservoir every 7 days for 70 days and incubated at 37 degrees C. Student's t test was used to determine whether there was a difference in spreader penetration between the groups, and a Fisher's exact test was used to determine whether there was a difference in bacterial leakage. The positive and negative controls validated the testing model. When a .02 tapered master cone was used, the spreader penetrated significantly closer to working length than when a .06 tapered master cone was used (p < 0.05). The difference between the groups in the number of samples that demonstrated complete bacterial penetration was not significant (p > 0.05). PMID- 11771593 TI - Degradation of the sealing properties of a zinc oxide-calcium sulfate-based temporary filling material by entrapped cotton fibers. AB - During root canal therapy cotton may be placed in the pulp chamber before placement of a temporary filling. This study evaluated the effect on the sealing of a zinc oxide-calcium sulfate-based temporary filling material when fibers of the internal cotton passed through the filling material and reached the external surface of the temporary filling. Glass tubes were filled with a 3.5 mm thickness of the temporary filling incorporating a bundle of cotton fibers that passed from the inner surface of the restoration to the outer surface. The time for methylene blue stain to penetrate the filling was compared among four groups. Group 1 (large bundles of fibers) had 20 to 40 fibers, group 2 (medium bundles) had 10 to 15 fibers, group 3 (small bundles) had 3 to 5 fibers, and group 4 (negative controls) had no cotton fibers. All samples with cotton fibers leaked within 12 min. None of the negative controls leaked within the 21 -day observation time. These results demonstrate that even a very small amount of cotton trapped between the wall of the tube and the filling material dramatically reduced the sealing quality of the temporary restoration. PMID- 11771594 TI - Epidemiological evaluation of the outcomes of nonsurgical root canal treatment in a large cohort of insured dental patients. AB - Selected outcomes following initial nonsurgical root canal treatment (NSRCT) procedures were retrospectively assessed using an insurance company database of 110,766 nonsurgical root canal procedures that were completed by endodontists and their referring general dentists. A subset of 44,613 cases, with a minimum required follow-up time of 2 yr, showed incidences of extraction, retreatment and periradicular surgery equal to 5.56%, 2.47%, and 1.41%, respectively. The incidence of subsequent extraction increased with patient age. Teeth that were not restored after root canal therapy were significantly more likely to undergo extraction than restored teeth. Although the practice pattern for endodontists consisted of a significantly higher proportion of molars (48% more; p < 0.001) and a smaller proportion of anterior teeth (43% less; p < 0.001) than general dentists, both groups of providers had comparable rates of untoward events. These data strongly support the hypothesis that the specialist practice provides similar rates of clinical success compared with other providers, even when treating significantly more complex NSRCT cases. Overall, 94.44% of nonsurgical root canal treated teeth remained functional over an average follow-up time of 3.5 yr. These results are an important indication of the benefits of endodontic treatment when provided in an integrated health care delivery system of endodontists and their referring general dentists. PMID- 11771595 TI - Use of rotational tomography for assessing internal resorption. AB - The authors describe the use of tomography, a relatively simple and well established radiographic technique, for determining the buccolingual extent of internal resorptive lesions. The procedure may be a useful adjunct in selected cases to determine whether root canal therapy for the treatment of internal resorption followed by restoration of the tooth is likely to be successful. PMID- 11771596 TI - Malignant lymphoma of the maxillary sinus manifesting as a persistent toothache. AB - Many teeth have been mistakenly extracted or endodontically treated because of an incorrect diagnosis of orofacial pain, including toothache. A case of persistent toothache originating from a malignant lymphoma of the left maxillary sinus is presented. Root canal therapy and extraction of the upper left quadrant teeth from the canine to the second molar did not resolve the chief complaint. The patient was referred to a neurologist and received a diagnosis of a malignant lymphoma, a rare lesion of the maxillary sinus. This case stresses the importance of considering malignant neoplasm of the maxillary sinus as a potential etiologic factor in the differential diagnosis of orofacial pain. PMID- 11771597 TI - Induction agents: "Avertin.". PMID- 11771598 TI - Propofol anaesthesia via target controlled infusion or manually controlled infusion: effects on the bispectral index as a measure of anaesthetic depth. AB - Target controlled infusions (TCI) of propofol allow anaesthetists to target constant blood concentrations and respond promptly to signs of inappropriate anaesthetic depth. Studies comparing propofol TCI with manually controlled infusion (MCI) reported similar control of anaesthesia, but did not use an objective measure of anaesthetic depth. We therefore tested whether the Bispectral Index (BIS), an electroencephalographic (EEG) variable, is more stable during propofol TCI or MCI. Forty patients received midazolam and fentanyl before induction and were randomized to TCI or MCI. Target propofol concentrations in the TCI group were 3 to 8 microg/ml. The MCI group received propofol bolus (approximately 2 mg/kg) and infusion (3 to 10 mg/kg/h). Neuromuscular blockade was achieved with rocuronium. Following endotracheal intubation, nitrous oxide (66%) in oxygen was delivered and propofol infusion and fentanyl boluses were titrated against clinical signs. Blood pressure, heart rate and EEG were recorded, although the anaesthetist was blind to BIS values. The ideal BIS for general anaesthesia was defined as 50. Performance error, absolute performance error, wobble and divergence of BIS, and maximum changes in blood pressure and heart rate were compared using two-sample t-tests or rank-sum tests where appropriate. There was no difference in absolute performance errors during maintenance of anaesthesia with propofol TCI or MCI (23 +/- 11% vs 23 +/- 9%; P=0.97). The two groups did not differ significantly in performance error, wobble, divergence on haemodynamic changes. We conclude that TCI and MCI result in similar depth of anaesthesia and haemodynamic stability when titrated against traditional clinical signs. PMID- 11771599 TI - Comparison of three methods to estimate plasma bicarbonate in critically ill patients: Henderson-Hasselbalch, enzymatic, and strong-ion-gap. AB - We have previously found poor agreement between Henderson-Hasselbalch and enzymatic methods for estimating plasma bicarbonate concentration in critically ill patients. In this study we compared these two established methods with a new method for estimating bicarbonate using the strong-ion-gap equation. The strong ion-gap is derived from the Stewart approach to acid-base physiology. One hundred data sets were collected from records of routine daily blood samples in critically ill patients. Bland-Altman analyses were used to compare the three methods. We proposed that bias greater than +/- 1 mmol/l and limits of agreement wider than bias +/- 2 mmol/l were clinically important, Comparing the Henderson Hasselbalch method to the enzymatic method, the bias was 2.1 mmol/l and the limits of agreement were -1.8 mmol/l to 5.9 mmol/l. Comparing the Henderson Hasselbalch method to the strong-ion-gap method, the bias was -9.1 mmol/l and the limits of agreement were -17.1 mmol/l to -1.1 mmol/l. Comparing the enzymatic to the strong-ion-gap method, the bias was -11.2 mmol/l and the limits of agreement were -18.2 mmol/l to -4.2 mmol/l. This study found poor agreement between the two established bicarbonate assays and worse agreement between the established assays and the strong-ion-gap method. The strong-ion-gap method is currently too inaccurate for clinical application, but may have future use. PMID- 11771600 TI - Human serum albumin induced hypotension in the postoperative phase of cardiac surgery. AB - Hypotension associated with the rapid infusion of human serum albumin products was first recognised in Australasia in the early 1970s. An association with the angiotensin converting enzyme inhibitor class of drugs (ACE-I) followed, leading to a proposed mechanism involving bradykinin generation through pre-kallikrein activator (PKA) presence in the infused fluid. The newer generation albumin products (Albumex) contain very low concentrations of PKA and are generally thought safe to use in most patient populations. Anecdotal reports of paradoxical hypotension with rapid infusion of 4% albumin in our department led to an audit of practice over three months. Four out of 36 patients (11%) who received 4% albumin intravenously experienced paradoxical hypotension. Three of these patients were taking ACE-I preoperatively (P=0.04). There was no observed hypotension associated with intravenous infusion of crystalloid fluid. We believe 4% albumin should be used with caution, particularly in those patients receiving ACE-I preoperatively. PMID- 11771601 TI - Post dural puncture headache following combined spinal epidural or epidural anaesthesia in obstetric patients. AB - A retrospective review of obstetric anaesthesia charts was performed for all parturients receiving regional anaesthesia over a 22-month period. The incidence of headache, post dural puncture headache (PDPH) and various other complications of regional anaesthesia that had been prospectively assessed were noted, as was the anaesthetic technique used (epidural or combined spinal epidural (CSE)). PDPH was rare (0.44%) and occurred with similar frequency in those managed with either epidural or CSE anaesthesia or analgesia. The pencil-point spinal needle gauge (27 or 29) did not influence the incidence of PDPH. Following a CSE technique, the epidural catheter more reliably produced effective analgesia/anaesthesia as compared with a standard epidural technique (1.49% versus 3.18% incidence of replaced catheters respectively). We conclude, based on the results of this retrospective review, that CSE is acceptable with respect to the occurrence of PDPH and that it is possible it is advantageous in relation to the correct placement of the epidural catheter PMID- 11771602 TI - The effect of the biopatch, a chlorhexidine impregnated dressing, on bacterial colonization of epidural catheter exit sites. AB - We performed a prospective, randomized study in 55 ASA I to 3 women undergoing elective gynaecological surgery followed by postoperative epidural analgesia. We compared the incidence of bacterial colonization at the epidural exit site following catheter removal between a control group and an experimental group who received a chlorhexidine impregnated dressing (Biopatch, Johnson and Johnson, Arlington, TX, U.S.A.). Positive culture results were found in 11 of 27 (40.1%) patients in the control group compared with one of 29 (3.4%) patients whose epidural catheters were dressed with the Biopatch. We concluded that the Biopatch was effective in reducing bacterial colonization of the epidural catheter exit site. PMID- 11771603 TI - Laryngeal mask vs intubating laryngeal mask: insertion and ventilation by inexperienced resuscitators. AB - The laryngeal mask airway (LMA) has been shown to be useful in airway maintenance during resuscitation. The intubating laryngeal mask (ILM) is a modified LMA permitting both ventilation and rapid endotracheal intubation. We aimed to compare the LMA and the ILM with regard to ease of insertion and successful ventilation by inexperienced personnel. We have used anaesthetized, apnoeic, non paralysed patients as a model to simulate resuscitation. Following standardized training, non-anaesthetic medical staff with no previous experience in laryngeal mask airway insertion (novices) inserted either the LMA or ILM in 55 patients following induction of anaesthesia. There were no differences between the two patient groups included in our study with regard to mean age and body mass index (BMI). The success rate for inserting the airway device and achieving a significant end-tidal CO2 recording within two minutes was 23/28 for the LMA (82.1%) and 22/27 for the ILM (81.5%). Reasons for failure included inability to insert the ILM past the teeth and insertion of the LMA upside down. There were no clinically relevant differences in the mean time to airway insertion and successful ventilation (62.6 vs 62 seconds) or expired tidal volume (781 vs 767 ml) for the LMA and ILM respectively. We conclude that the ILM is as easily inserted and effectively used as an LMA by novices and, because it allows the option offacilitating endotracheal intubation, may be the preferred device for maintaining an airway during resuscitation. PMID- 11771604 TI - A new technique for difficult intubations. AB - A Macintosh laryngoscope was modified to allow a rigid fibreoptic scope to be attached. Our purpose was to determine if Cormack and Lehane scores could be improved using the described fibreoptic technique, thus allowing easier intubating conditions. In order to assess its value for intubation, a study was performed on 53 patients. Thirty-three of these patients were classified to be difficult intubations (suspected or unanticipated). The Cormack and Lehane scores were improved by the use of the modified laryngoscope by one to three grades compared to the standard laryngoscopy. Significantly improved intubating condition were observed. The assessment demonstrates that many patients with Mallampati scores of III and IV can be successfully managed by this technique. PMID- 11771605 TI - A randomized trial comparing two laryngeal mask airway insertion techniques. AB - This study was undertaken to compare laryngoscopic-guided LMA insertion with a standard insertion technique. A total of 149 patients undergoing elective general surgical and orthopaedic procedures were randomly divided into two groups. Study endpoints included ease of insertion, haemodynamic changes, local trauma bleeding, and postoperative sore throat. There were no statistically significant differences found. The laryngoscope may aid laryngeal mask airway insertion in some circumstances. PMID- 11771606 TI - Sevoflurane drawover anaesthesia with two Oxford Miniature Vaporizers in series. AB - The output of sevoflurane from a drawover system utilizing two Oxford Miniature Vaporizers (OMVs) in series has been shown in bench-testing to be predictable. We have shown that adequate anaesthesia can be achieved with one vaporizer in most situations if an intravenous induction is used. Occasionally a second vaporizer is necessary to deepen the level of anaesthesia. For an inhalational technique to be successful it is necessary to use both vaporizers from the outset. Under these conditions, adequate operating conditions are easily produced. The method could be useful in field or military applications. PMID- 11771607 TI - Enteral nutrition in the critically ill: a prospective survey in an Australian intensive care unit. AB - Nutritional support is routine practice in critically ill patients and enteral feeding is preferred to the parenteral route. However this direct delivery of nutrients to the gut is potentially ineffective for a variety of reasons. We performed a prospective audit of 40 consecutive intensive care patients to determine whether enteral feeding met the nutritional requirements of our patients. The ideal requirements for each patient were calculated using the Harris-Benedict equation with an adjustment determined by the patient's diagnosis. We compared the amount of feed delivered with the daily requirements over a seven-day period Successful feeding was defined as the achievement of 90% of the ideal calorie requirement for two consecutive days. The mean calculated (+/- SD) energy requirement was 9,566 kJ (+/- 2,586). Patients received only 51% (SD 38) of their energy requirements throughout the study period. Only 10 patients (25%) were successfully fed for at least any two-day period in the seven days. Feeding was limited mainly by gastrointestinal dysfunction or by the need to fast the patient for medical, surgical and airway procedures. Success of feeding was not related to the use of sedative orparalysing agents and had no correlation with plasma albumin concentration. There was no difference in the volume of feed delivered to patients who survived or died. Prokinetic agents were used in 25 patients and in these patients there was a trend towards improved delivery of feed. PMID- 11771608 TI - Current usage of dopamine in New Zealand intensive care units. AB - A nation-wide evaluation of dopamine usage in New Zealand Intensive Care Units (ICUs) was undertaken. Twenty-six public hospital ICUs participated. Twenty-two ICUs (85%) use dopamine as an inotrope. Seventeen ICUs use dopamine for presumed selective renal effects at least occasionally, but with wide variation in what is considered to be "renal-dose". Level 3 ICUs were less likely to use "renal-dose" dopamine than levels 1 and 2 (P= 0.01). Nineteen units (83%) use weight referenced (i.e., microg x kg(-1) x min(-1)) dopamine administration. Weight referenced administration and "renal-dose" dopamine were likely to be in use together (P=0.02). Standard dopamine dilutions varied widely with a median of 2 mg x ml(-1) (range 0.4 to 8 mg x ml(-1)). Given a demonstrated association between weight-referenced administration and "renal-dose" dopamine, along with particular pharmacokinetic and pharmacodynamic reservations, the value of weight referenced administration of dopamine in adult patients is questioned. PMID- 11771609 TI - r-hirudin as anticoagulant for cardiopulmonary bypass. AB - A 68-year-old woman with unstable angina and an episode of ventricular fibrillation developed a persistent and recurrent rash due to heparin. Medical therapy was continued with danaproid. For cardiopulmonary bypass and coronary artery grafting, r-hirudin was used as the anticoagulant. There were no thrombotic or coagulopathic complications. There is still no ideal alternative to unfractionated heparin for anticoagulation for cardiopulmonary bypass. The use of r-hirudin was successful and we describe our anticoagulant strategy. PMID- 11771610 TI - Haemodynamic compromise during thoracoscopic/laparoscopic oesophagectomy. AB - Minimally invasive oesophagectomy is a relatively new procedure that is performed by means of thoracoscopy and laparoscopy. One stage of the procedure involves creation of a peritoneo-pleural communication in the presence of a pneumoperitoneum. In the case presented, severe hypotension occurred at this point. We believe this was caused by the escape of carbon dioxide from the peritoneal cavity into the right hemithorax, resulting in tension pneumothorax and cardiac tamponade. We believe this to be a predictable complication of this procedure but one that if expected, recognised and correctly managed, should not result in adverse outcomes. PMID- 11771611 TI - Echocardiographic diagnosis of extrapericardial tamponade due to dilated gastric roll following oesophagectomy. AB - A complication of lower thoracic oesophagectomy for oesophageal carcinoma is reported. Extrapericardial tamponade was caused by a dilated retrosternal gastric roll. Echocardiography was useful for diagnosis. Diagnosis, investigation and management of this unusual but life-threatening complication are discussed. Transthoracic echocardiography is a useful and practical investigation for the evaluation of complications of oesophagectomy. PMID- 11771612 TI - Pneumomediastinum after dental surgery. AB - A previously healthy woman presented with chest pain and cervical swelling several hours after undergoing surgical removal of third molar teeth. Mediastinal and subcutaneous emphysema was demonstrated by chest X-ray. Air had been introduced under the soft tissue flap by the high-speed turbine drill used to remove the alveolar bone, rather than the air/water syringe. Surgical handpieces that vent the air away from the surgical field should be used during such procedures. The mediastinal and subcutaneous air resolved after oxygen administration. PMID- 11771613 TI - Unexpected difficult intubation in a patient with normal airway on assessment. AB - Routine preoperative assessment of the patient's airway includes an assessment of mouth opening and a grading of the view according to the Mallampati scale. This is carried out with the patient sitting and actively opening the mouth without phonation. This case report illustrates that the temporomandibular joint is a complex joint and that certain pathologies may prevent passive depression of the mandible after induction of anaesthesia. PMID- 11771614 TI - Venous air embolism during liver transplantation. PMID- 11771615 TI - Awake craniotomy. PMID- 11771616 TI - Intrahospital transport of critically ill patients. PMID- 11771617 TI - Wheels on medical equipment. PMID- 11771618 TI - Availability of parenteral quinine. PMID- 11771619 TI - Unexpected difficulty administering an epidural top-up for caesarean section. PMID- 11771620 TI - Problems with the rubber stopper of a propofol ampoule. PMID- 11771621 TI - Impaired production priming and intact identification priming in Alzheimer's disease. AB - This study examined the distinction between identification and production processes in repetition priming for 16 patients with Alzheimer's disease (AD) and 16 healthy old control participants (NC). Words were read in three study phases. In three test phases, participants (1) reread studied words, along with unstudied words, in a word-naming task (identification priming); (2) completed 3-letter stems of studied and unstudied words into words in a word-stem completion task (production priming); and (3) answered yes or no to having read studied and unstudied words in a recognition task (explicit memory). Explicit memory and word stem completion priming were impaired in the AD group compared to the NC group. After correcting for baseline slowing, word-naming priming magnitude did not differ between the groups. The results suggest that the distinction between production and identification processes has promise for explaining the pattern of preservation and failure of repetition priming in AD. PMID- 11771622 TI - Script knowledge after severe traumatic brain injury. AB - Severe diffuse traumatic brain injury (TBI) may impair the performance of daily life complex activities. The aim of the present study was to assess whether these difficulties are related to a representational impairment of action knowledge. Two tasks requiring the manipulation of scripts were used. The first (script reconstitution) required subjects to sort cards describing actions belonging to 4 different scripts, presented in a random order. The second (script generation) required subjects to generate actions belonging to a given script. The results showed that TBI patients had preserved access to goal representation and action knowledge. However, they demonstrated (1) significant impairments when they had to deal with simultaneous competing sources of information and (2) a lack of inhibitory control on routine overlearned skills. Patients' performance was significantly correlated with behavioral modifications in everyday life. These data suggest that action impairment in severe TBI patients cannot be attributed to an impairment of action knowledge per se. As previously suggested by Schwartz et al., a restriction of limited-capacity processing resources may account for the observed deficits. PMID- 11771623 TI - Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine guanine phosphoribosyltransferase deficiency. AB - Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involves the nearly complete absence of an enzyme (hypoxanthine-guanine phosphoribosyltransferase, or HPRT) that is essential for purine salvage. In addition to hyperuricemia, all patients with classic LND suffer from movement disorder and compulsive self-injury, and most have mental retardation. Patients with partial HPRT deficiency (variants) always have hyperuricemia and often have neurologic abnormalities, but do not self-injure and usually are described as having normal intelligence. Here we compare 15 patients with LND to 9 variants and 13 normal adolescents and adults. Testing revealed unambiguous and qualitatively similar cognitive deficits in both patient groups. The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND. PMID- 11771624 TI - Rate of cognitive change in Alzheimer's disease: methodological approaches using random effects models. AB - Subtraction of serial scores, Least Squares Estimators, and Best Linear Unbiased Predictors (BLUPs) were compared for estimating rates of cognitive change for Mini-Mental State Exam (MMSE) and Dementia Rating Scale (DRS) scores for 299 probable Alzheimer's disease patients. The BLUPs provided cleaner group estimates of subjects' intercepts and slopes and are preferred. Regression analysis of the BLUP estimates of rate of change indicated that steeper declines were associated with higher levels of education and older age at onset. These effects were much smaller than those due to estimated initial cognitive test score. Differences in longitudinal metric characteristics of the MMSE and DRS were found, with the DRS yielding more precise change estimates. We discuss modeling these longitudinal data, and discuss use of the estimates of rate of change and intercept as data in their own right. PMID- 11771625 TI - Acalculia: deficits of operational and quantity number knowledge. AB - We describe the standardization of three new tests of knowledge of quantity facts, number operations and multiplication facts. We also report a validation study in which a group of 50 patients with cortical degenerative disorders were tested on these three new tests of number processing. Our results show that the quantity facts and number operations tests are sensitive measures of number processing abilities. Performance on the three new tests and the Graded Difficulty Arithmetic (GDA) test were found to be significantly impaired in the Alzheimer's Disease (AD) group. The frontotemporal dementia (FTD) group was subdivided into those with a semantic dementia (SD) and those with prominent frontal features (Non-SD). The semantic dementia subgroup was more impaired than both the AD patient group and the nonsemantic FTD subgroup on the quantity facts test. A more fine grained analysis reveals several interesting patterns of performance, including a dissociation between impaired performance on the quantity facts and number operations tests and preserved performance on the GDA. The findings attest the value of comparing performance on the GDA and our new tests in delineating the nature of an individual's number processing deficits. Implications for the relation between simple arithmetic fact knowledge and higher level number processing are discussed. PMID- 11771626 TI - Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses. AB - Gulf War unexplained illnesses (GWUI) are a heterogeneous collection of symptoms of unknown origin known to be more common among veterans of the Gulf War than among nonveterans. In the present study we focused on one of these unexplained illnesses. We tested the hypothesis that in a sample of Persian Gulf War veterans chronic fatigue syndrome (CFS) was associated with cognitive deficits on computerized cognitive testing after controlling for the effects of premorbid cognitive differences. We obtained Armed Forces Qualification Test (AFQT) data acquired around the date of induction into the military on 94 veterans of the Gulf War, 32 with CFS and 62 healthy controls. Controls performed better than participants diagnosed with CFS on the AFQT. Cognitive deficits were associated with CFS on 3 of 8 variables after the effect of premorbid AFQT scores was removed with ANCOVA. PMID- 11771627 TI - Assessment of calculation and number processing using the EC301 battery: cross cultural normative data and application to left- and right-brain damaged patients. AB - To provide referential normative data on simple tasks dealing with number processing and calculation which could be used in clinical investigations, 551 normal volunteers aged between 18 and 69 years from France and Belgium (n = 180). Italy (n = 212) and Germany (n = 159). performed the 31 tasks which constitute the EC301 calculation and number processing battery. Differences between countries were significant for 16 tasks and a Gender x Education interaction was observed for some tasks, with men performing better than women among subjects with low education only. To present an overview of preserved and impaired calculation and number processing abilities in left-brain damaged (LBD) aphasic patients and right-brain damaged (RBD) nonaphasic patients, the 31 subtests of the EC301 battery were proposed to 80 patients with cerebrovascular accident, 56 left and 24 right, for most cases in the territory of the middle cerebral artery. LBD aphasic patients showed low performance on oral and alphabetical spoken verbal and written verbal counting, transcoding when a written code was involved, and mental or written calculation; but relatively good performance at finding the number of elements in small sets, comparing numbers written in the Arabic digital code and placing correctly numbers on an analogue number line. The lowest performances of RBD patients were observed for estimation tasks and for placing a number on a scale. Results and their implications for further research are discussed according to the present information processing and anatomofunctional models of calculation and number processing. PMID- 11771628 TI - Exploring the clinical utility of WAIS-III and WMS-III. PMID- 11771629 TI - WAIS-III reliability data for clinical groups. AB - Reliability estimates for psychological tests are almost always reported for nonclinical populations (e.g., the normative samples). Such practice will no longer be sufficient as the new standards for testing call for an adequate assessment of psychometric properties within the specific population being tested. The purpose of this study was to provide internal consistency reliability estimates for clinical groups on the Wechsler Adult Intelligence Scale-Third Edition. The study included data from 403 clinical participants composed of 10 groups of adults recruited as part of the WAIS-III clinical validity studies. Split-half reliability coefficients were obtained for these groups replicating the procedure used in the WAIS-III. With 8 of the clinical groups, the split-half reliability coefficients were comparable to, or even higher than, those reported for the WAIS-III standardization sample. In general, the split-half coefficients for the Verbal subtests tended to be higher than the coefficients for the Performance subtests. The high magnitude and general pattern of these coefficients demonstrate that the WAIS-III scales do not include additional error variance above and beyond what is reported in the WAIS-III-WMS-III Technical Manual when it was used to assess certain clinical groups. For the ADHD/ADD and learning disabilities groups, however, the internal consistencies coefficients of some subtests were relatively lower, although not statistically significant, than the normative sample. These findings may reflect more heterogeneity within the groups. The implications for assessment and for using alternate methods of determining the psychometric properties in these populations are discussed. PMID- 11771630 TI - Sensitivity and specificity of WAIS-III/WMS-III demographically corrected factor scores in neuropsychological assessment. AB - This study explored the neurodiagnostic utility of 6 factor scores identified by recent exploratory and confirmatory factor analyses of the WAIS-III and WMS-III: Verbal Comprehension, Perceptual Organization, Processing Speed, Working Memory, Auditory Memory and Visual Memory. Factor scores were corrected for age. education, sex and ethnicity to minimize their influences on diagnostic accuracy. Cut-offs at 1, 1.5 and 2 standard deviations (SDs) below the standardization sample mean were applied to data from the overlapping test normative samples (N = 1073) and 6 clinical samples described in the WAIS-III/WMS-III Technical Manual (N = 126). The analyses suggest that a I SD cut-off yields the most balanced levels of sensitivity and specificity; more strict (1.5 or 2 SD) cut-offs generally result in trading modest gains in specificity for larger losses in sensitivity. Finally, using combinations of WAIS-III/WMS-III factors together as test batteries, we explored the sensitivity and specificity implications of varying diagnostic decision rules (e.g.,1 vs. 2 impaired factors = "impairment"). For most of the disorders considered here, even a small (e.g., 3 factor) WAIS III/WMS-III battery provides quite good overall diagnostic accuracy. PMID- 11771631 TI - The influence of IQ stratification on WAIS-III/WMS-III FSIQ-general memory index discrepancy base-rates in the standardization sample. AB - Since memory performance expectations may be IQ-based, unidirectional base rate data for IQ-Memory Score discrepancies are provided in the WAIS-III/WMS-III Technical Manual. The utility of these data partially rests on the assumption that discrepancy base rates do not vary across ability levels. FSIQ stratified base rate data generated from the standardization sample, however, demonstrate substantial variability across the IQ spectrum. A superiority of memory score over FSIQ is typical at lower IQ levels, whereas the converse is true at higher IQ levels. These data indicate that the use of IQ-memory score unstratified "simple difference" tables could lead to erroneous conclusions for clients with low or high IQ. IQ stratified standardization base rate data are provided as a complement to the "predicted difference" method detailed in the Technical Manual. PMID- 11771632 TI - WMS-III performance in patients with temporal lobe epilepsy: group differences and individual classification. AB - The utility of the WMS-III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory-Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS-III scores, the Auditory-Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS-III in detecting laterality may be limited in preoperative cases, the WMS-III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery. PMID- 11771633 TI - Criterion validity of new WAIS-II subtest scores after traumatic brain injury. AB - The criterion validity of the new subtests from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III; Wechsler, 1997) was evaluated in a sample of 100 patients with traumatic brain injury (TBI). Letter-Number Sequencing and Symbol Search, but not Matrix Reasoning, yielded statistically significant differences in performance between patients with moderate-severe TBI, patients with mild TBI, and demographically matched controls. Level of education accounted for a statistically significant amount of variance in the performance of patients with TBI, in addition to that explained by injury severity variables. It is concluded that Letter-Number Sequencing and Symbol Search have satisfactory criterion validity, but that they need to be supplemented with other measures in the context of neuropsychological evaluations. Matrix Reasoning, on the other hand, is not sensitive to the sequelae of TBI and more studies are needed to determine how it can be used for neuropsychological assessment purposes. PMID- 11771634 TI - Vicarious annihilation: the effect of mortality salience on perceptions of hate crimes. AB - Previous research has found that reminding participants of their mortality creates a need for individuals to maintain and defend subjective cultural worldviews. As a result, mortality salient participants typically strive to uphold legal sanctions and also react negatively to individuals who espouse alternative worldview beliefs, exhibiting behaviors toward those targets ranging from verbal derogation to physical aggression. This paper extends this line of research by examining perceptions of hate crimes. Hate crimes represent a unique class of crime where both the perpetrator and victim may be viewed as worldview violators. Study 1 revealed that mortality salient participants were more supportive of hate crime legislation than were control participants when hate crimes were described in abstract terms and no specific victim was mentioned. In Study 2, a specific victim who posed a potential worldview threat was identified. In this case, mortality salient participants were less punitive toward offenders who attacked these specific worldview-threatening victims. PMID- 11771635 TI - The relationship between psychopathic personality features and malingering symptoms of major mental illness. AB - This study examined the relationship between psychopathy and malingering in a subsample of male prison inmates (n = 55) participating in a larger study of the clinical utility of various assessment measures in correctional settings. Participants' capacity to feign major mental illness successfully was evaluated using standard cutoff scores for the detection of malingering on a variety of instruments, including the Structured Inventory of Malingered Symptomatology (SIMS; G. P Smith & G. O. Burger, 1997), the Structured Interview of Reported Symptoms (SIRS; R. Rogers, R. M. Bagby, & S. E. Dickens, 1992), and the Personality Assessment Inventory (PAI; L. Morey, 1991). Psychopathic traits were assessed via the Psychopathic Personality Inventory (PPI; S.O. Lilienfeld & B. P Andrews, 1996). Correlations between the malingering indices and the PPI were low (-.14 to .14) and not statistically significant. These findings fail to support the clinical intuition that individuals with higher levels of psychopathy are likely to be more adept at malingering. PMID- 11771636 TI - Is that what I said?: witnesses' responses to interviewer modifications. AB - Modifications occur when interviewers contradict statements made by witnesses or imply that witnesses provided information that they (interviewers) did not provide. Because of their suggestive nature, modifications threaten the reliability of investigative interviews. This study investigated developmental differences in witnesses' responses to modifications during interviews as well as in inclusion of modified misinformation in subsequent answers. Preschool, elementary school, and college students were interviewed about a video presentation. In the experimental conditions, the interviewer contradicted information about the video provided by the participants. Participants then answered two sets of follow-up questions: one immediately following the interview and another 6-8 days later. Results indicated that participants were more likely to ignore modifications than to correct or agree with them. Adult participants were most likely to disagree with modifications. Preschoolers were most likely to incorporate modified misinformation into subsequent answers. Implications of these findings for investigative interviews are discussed. PMID- 11771637 TI - Stereotyping ricochet: complex effects of racial distinctiveness on identification accuracy. AB - Stuidies show that distinctive (e.g., attractive) people are better remembered than typical people (B. L. Cutler & S. D. Penrod, 1995). We investigated the effect of a Black person's presence on recognition accuracy for surrounding White individuals. Regarding eyewitness accuracy for an event, we expected more errors for White targets accompanied by Black confederates (experimental condition) than by White confederates (control). A staged accident was witnessed by participants, followed by a lineup. In 3 experiments, identification accuracy decreased in the experimental conditions, relative to control. Further data suggested that attention focused on the Black confederate reduced memory for the other confederates at the event. This pattern did not generalize to a condition substituting garish hair color for race, suggesting that racial distinctiveness, rather than general physical distinctiveness, contributed to the prior results. PMID- 11771638 TI - Actuarial assessment of sex offender recidivism risk: a cross-validation of the RRASOR and the Static-99 in Sweden. AB - We cross-validated two actuarial risk assessment tools, the RRASOR (R. K. Hanson, 1997) and the Static-99 (R. K. Hanson & D. Thornton, 1999), in a retrospective follow-up (mean follow-up time = 3.69 years) of all sex offenders released from Swedish prisons during 1993-1997 (N = 1,400, all men, age > or =18 years). File based data were collected by a researcher blind to the outcome (registered criminal recidivism), and individual risk factors as well as complete instrument characteristics were explored. Both the RRASOR and the Static-99 showed similar and moderate predictive accuracy for sexual reconvictions whereas the Static-99 exhibited a significantly higher accuracy for the prediction of any violent recidivism as compared to the RRASOR. Although particularly the Static-99 proved moderately robust as an actuarial measure of recidivism risk among sexual offenders in Sweden, both procedures may need further evaluation, for example, with sex offender subpopulations differing ethnically or with respect to offense characteristics. The usefulness of actuarial methods for the assessment of sex offender recidivism risk is discussed in the context of current practice. PMID- 11771639 TI - Investigation of the criminal and conditional release profiles of Canadian federal offenders as a function of psychopathy and age. AB - Using the Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) diagnostic cut off score of 30, the complete criminal career and community release profiles of 317 Canadian federal offenders (224 low scorers and 93 scoring within the psychopathic range) were investigated. Adult crimes were coded according to age at commission as well as either violent, nonviolent, or nonsexually violent. Changes in performance following release into the community also were examined. Results indicated that offenders scoring within the psychopathic range consistently committed more violent and nonviolent crimes than their counterparts for about three decades, spanning their late adolescence to their late 40s. Numbers of nonviolent criminal offenses committed by high PCL-R scorers declined considerably after age 30 relative to violent offenses, which declined and then rebounded in the late 30s before a major reduction was evidenced. Throughout adulthood, high PCL-R scorers failed during community release significantly faster than did low scorers. Importantly, from a risk management perspective, the release performance of low PCL-R scorers improved with age, whereas the opposite was seen for high scorers. Further, offenders scoring high on the PCL-R did not show a lower charge to conviction ratio with age, suggesting that they may not have been getting better at manipulating the legal system. PMID- 11771640 TI - Chair's introduction: sodium channels and neuronal dysfunction--emerging concepts, converging themes. PMID- 11771641 TI - Sodium channel gene expression and epilepsy. AB - Na+ channelopathies that prolong membrane depolarization lead to neuronal bursting, abnormal network synchronization, and various patterns of episodic neurological disorders, including epilepsy. Two distinct pathways exist for generating epileptic phenotypes based on inherited disorders of voltage-gated Na+ ion channels. The first pathway is direct, involving mutations in genes encoding the pore-forming alpha1 and regulatory beta subunits of the channel that directly alter current amplitude or kinetics. These mutations favour repetitive firing and network hyperexcitability, although often the circuits most vulnerable to functional alterations are not easy to identify and the emergent clinical phenotypes are difficult to predict. The second pathway involves mutation of other genes that lead to downstream modifications in Na+ channel expression. Two clinically relevant examples of localization-related vulnerability in brain are described that illustrate how specific phenotypes arise from both direct and secondary pathways. Selective expression of the cardiac SCN5A channel within limbic regions of brain may explain why mutation of the gene for this tetrodotoxin-insensitive current may be associated with seizures. Ectopic expression of type II Na+ channels along axonal internodes in hypomyelinated brain may reveal why deletion of the myelin basic protein gene leads to subcortical seizure patterns. Analysis of these models offers insight into developmental processes that control the cellular expression and plasticity of Na+ channel genes, and will help to clarify mechanisms of hereditary Na+ channel based epileptogenesis. PMID- 11771642 TI - Beta subunits: players in neuronal hyperexcitability? AB - Voltage-gated Na+ channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian Na+ channels are heterotrimers, composed of a central, pore forming a subunit and two auxiliary beta subunits. The a subunits form a gene family with at least 10 members. Mutations in alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalaemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode Na + channel beta subunits with at least one alternative splice product. A mutation in the beta1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS+1) in a human family with this disease. Na+ channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure function studies have resulted in the preliminary assignment of functional domains in the beta1 subunit. A Na+ channel signalling complex is proposed that involves beta subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTPbeta, and extracellular matrix molecules such as tenascin. PMID- 11771643 TI - Modulation of sodium channels in primary afferent neurons. AB - Electrophysiological studies have revealed that the properties of voltage-gated Na+ channels can be modified by phosphorylation. Na+ channels have multiple sites for phosphorylation by protein kinases A and C (PKA and PKC). A change in the phosphorylation state of Na+ channels is an important mechanism of neuromodulation for both central and peripheral neurons. In isolated primary afferent sensory neurons, application of an inflammatory mediator, prostaglandin E2 (PGE2), causes an increase in excitability associated with a hyperpolarizing shift in the activation curve of the tetrodotoxin-resistant (TTX-R) Na+ currents. The experimental evidence indicates that the effect of PGE2 is mediated by an elevation in cAMP levels and activation of PKA. This potentiation of TTX-R Na+ channel activity is in marked contrast to the inhibitory effects of PKA and PKC on tetrodotoxin-sensitive (TTX-S) currents in central neurons. Infection of dorsal root ganglion neurons with Herpes simplex virus (HSV) results in an abolition of excitability associated with a selective loss of both TTX-S and TTX R Na+ currents: voltage-gated Ca2+ and K+ channels are unaffected by HSV infection. The loss of Na+ current is due to a virally induced internalization process and requires extracellular Na+. PMID- 11771644 TI - Sodium channels in primary sensory neurons: relationship to pain states. AB - Electrophysiological studies of dorsal root ganglion (DRG) neurons, and the results of PCR, Northern blot and in situ hybridization analyses have demonstrated the molecular diversity of Na+ channels that operate in sensory neurons. Several subtypes of alpha-subunit have been detected in DRG neurons and transcripts encoding all three beta-subunits are also present. Interestingly, one alpha subunit, Na(v)1.8, is selectively expressed in C-fibre and Adelta fibre associated sensory neurons that are predominantly involved in damage sensing. Another channel, Na(v).3, is selectively up regulated in a variety of models of neuropathic pain. In this review we focus on Na+ channels that are selectively expressed in DRG neurons as potential analgesic drug targets. In the absence of subtype specific inhibitors, the production of null mutant mice provides useful information on the specialized functions of particular Na+ channels. A refinement of this approach is to delete Na+ channel genes flanked by lox-P sites in the sensory ganglia of adult animals, using viruses to deliver the bacteriophage Cre recombinase enzyme. PMID- 11771645 TI - Sodium channels and epilepsy electrophysiology. AB - We examined the electrophysiology of epilepsy in the simplest system that exhibits epileptiform activity: microisland cultures that contain only one neuron. Some of these solitary excitatory hippocampal neurons generate the 'ictal' epileptiform activity characteristic of seizures. These neurons have endogenous (non-transmitter-mediated) bursts of activity that last for many seconds and appear to be driven by a persistent Na+ current. We examined this persistent Na+ current at the single channel level by recording the late openings of Na+ channels using outside-out patch recordings. Phenytoin reduced the probability of these late channel openings, but had less effect on the early channel openings that make up the peak Na+ current. The reduction of late channel openings was larger with pulses to more depolarized voltages. In contrast, the effect on early channel openings was similar at all voltages. There was little effect of phenytoin on the duration of channel openings and no effect on open channel current. This suggests that the persistent Na+ current is crucial in generating seizures. A good strategy for selecting anticonvulsants may be to search for drugs that more selectively block the persistent Na+ current at depolarized voltages. Such drugs could combine effectiveness and reduced side effects. PMID- 11771646 TI - Therapeutic concentrations of local anaesthetics unveil the potential role of sodium channels in neuropathic pain. AB - Neuropathic pain is frequently associated with hyperexcitability of primary afferents, characterized by spontaneous impulses and repetitive firing. Electrophysiology and molecular biology reveal changes in dorsal root ganglion Na+ channels under conditions of neuropathic pain, but the manner by which these changes alter the physiology of sensory afferents remains unknown. Equally mysterious is the mechanism by which i.v. local anaesthetic-like Na+ channel blockers suppress neuropathic pain behaviour at concentrations well below those reported for channel inhibition. We have compared the anti-allodynic actions of i.v. lidocaine (L) and stereoisomers of mexiletine (R-M, S-M), in rats after spinal nerve ligation, with their ability: (1) to inhibit fast, tetrodotoxin sensitive neuronal Na+ currents, elicited by brief (1 ms) pulses, at 10 Hz, from 'resting' potentials (-80, -60 mV) and (2) to suppress the seconds long plateau and the repetitive firing produced in axons by slowing of Na+ channel inactivation (e.g. using scorpion alpha-toxins). Both L and R-M at 5-10 microM relieved allodynia; S-M was ineffective. Na+ currents also were inhibited by M, with affinities that were increased by both repetitive 'firing' (K(R,S) = 5 microM) and depolarization of the 'resting' membrane (K(R) = 15 microM; K(S) = 30 microM). Stereopotency ratios depended on the manner in which different states of the channel were inducted. Both L and M shortened the action potential's 'plateau' in alpha-toxin treated axons, without reducing the spike, and suppressed repetitive firing with IC(50)s = 5 microM, and no stereoselectivity. These findings together demonstrate that Na+ channel blockers, at 'therapeutic' concentrations, can inhibit neuronal hyperexcitability. PMID- 11771647 TI - Molecular mechanisms of gating and drug block of sodium channels. AB - Voltage-gated Na+ channels are composed of an alpha subunit of 260 kDa associated with beta subunits of 33-36 kDa. Alpha subunits have four homologous domains (I to IV) containing six transmembrane alpha helices (S1-S6). The S4 segments serve as voltage sensors and move outward to initiate activation. The S5 and S6 segments and the short membrane-associated loops between them form the pore. Fast inactivation is mediated by closure of an inactivation gate formed by the intracellular loop between domains III and IV. The 3-D structure of the inactivation gate has been determined bv NMR spectroscopy, revealing the conformation of the pore-blocking IFM motif. Peptide scorpion toxins that alter gating of Na+ channels bind to the extracellular ends of the IIS4 and IVS4 segments, trap them in either an activated or non-activated position, and thereby selectively alter channel activation or inactivation. Voltage sensor-trapping may be a general mechanism of toxin action on voltage-gated ion channels. Local anaesthetics block the pore of Na+ channels by binding to a receptor site in segment S6 in domains III and IV. Anticonvulsants and antiarrhythmic drugs also interact with this site. A high-affinity Na+ channel blocker has recently been developed with this site as its target. The emerging knowledge of the molecular mechanisms of Na+ channel gating and drug block may allow development of novel therapeutics for epilepsy, cardiac arrhythmia and persistent pain syndromes. PMID- 11771648 TI - Molecular basis for function in sodium channels. AB - Na+ channels earned their unique role in excitable cells because of two functional properties, finely honed by evolution. The first is their exquisite sensitivity to small changes of membrane potential: a depolarization of only 10 mV can increase open probability by as much as two orders of magnitude. The second is the rapidity with which they respond to changes of membrane potential: their gates begin to open tens of microseconds after a depolarization. These features are built into two sets of moving parts: voltage sensors that respond directly to changes of membrane potential, and gates that open and close in response to voltage sensor movement. We have explored these movements using a combination of electrophysiology, site-directed mutagenesis, cysteine accessibility scanning and photoactivated cross-linking using a bifunctional cysteine reagent. The main voltage sensors of Na+ channels are four homologous S4 segments, each of which has a unique functional role. These transmembrane segments are almost completely surrounded by hydrophilic crevices. The membrane electric field moves these positively charged helices through a short, hydrophobic 'gating pore'. The minimum contact between an S4 segment and its gating pore insure that a small movement can rapidly move several of its charged residues across the electric field. PMID- 11771649 TI - Diverse functions and dynamic expression of neuronal sodium channels. AB - Nearly a dozen genes encode different Na channels, sharing a common overall motif but with subtly different amino acid sequences. Physiological signatures have now been established for some Na+ channels and it is clear that, from a functional point of view, Na+ channels are not all the same: different channels can have different physiological characteristics, and they can play different roles in the physiology of excitable cells. Moreover, the expression of Na+ channels within neurons is not a static process. Plasticity of Na+ channel gene expression occurs in the normal nervous system, where it accompanies transitions between different physiological states (e.g. low-frequency versus high-frequency firing states) in some types of neurons. Maladaptive changes in Na+ channel gene expression also occur in some pathological neurons. For example, transection of the peripheral axons of spinal sensory neurons triggers downregulation of some Na+ channel genes and up-regulation of others, resulting in changes in Na+ current expression that produce hyperexcitability, thereby contributing to chronic pain. There is also recent evidence for the expression of normally silent Na+ channel genes in Purkinje cells in experimental models of demyelinating diseases and in a human disease, multiple sclerosis; this dysregulation of Na+ channel expression may interfere with neuronal function in these disorders. The diversity and dynamic nature of Na+ channel expression introduce a high degree of complexity into the nervous system and present challenges for neuroscientists. In addition, they may present therapeutic opportunities as selective modulators for various Na+ channel subtypes become available. PMID- 11771650 TI - Studies of multimodal gating of the sodium channel. AB - Chandler and Meves found that in squid axons perfused with NaF a small flow of Na+ ions persisted in the inactivated state, and that the Na+ channel therefore has more than one open state. Studies by Correa and Bezanilla on single patches in squid axons showed that such steady currents arose from reopening of the channel at a relatively low frequency. Currents with comparable properties are generated in mammalian brain cells and elsewhere. The existence of a third mode of gating was established by Patlak and Ortiz when they showed that in frog muscle fibres there were occasionally quite large bursts of late openings. Again, similar behaviour has been observed in other types of muscle and in brain cells. It is suggested that the voltage gating of all ionic channels involves a screw helical mechanism, operating in steps each transferring unit charge. For segment S4 in domain IV of Na+ channels, three charges have to be transferred to reach the initial open state, and a fourth for fast inactivation to take place. The single late openings in the inactivated steady state may be explained by the transfer of a fifth charge in IVS4, while the larger bursts of reopening involve a modulation of the mechanism of fast inactivation. PMID- 11771651 TI - Enhanced transmission of glutamate current flowing from the dendrite to the soma in rat neocortical layer 5 neurons. AB - The presence of tetrodotoxin (TTX)-sensitive slowly-inactivating Na+ channels in the dendrites of neocortical layer 5 neurons was tested by focal iontophoresis of glutamate on the dendrite while voltage clamping the soma and proximal dendrite. The glutamate-transmitted current was measured with the voltage clamp circuit. When the soma was depolarized the transmitted current increased indicating voltage-dependent properties in the dendrite. Over 50% of this increased voltage dependence was blocked by TTX indicating a large portion of the enhanced dendro somatic current was caused non-inactivating Na+ channel inward rectification. The glutamate-transmitted current measured with a voltage clamp of the soma at firing level was equal to the effective glutamate measured during repetitive firing. PMID- 11771652 TI - Mutations of voltage-gated sodium channels in movement disorders and epilepsy. AB - Spontaneous and induced mutations of neuronal Na+ channels in human patients and mutant mice result in a broad range of neurological-disease. Epilepsy, a disorder of neuronal hyperexcitability, has been associated with delayed inactivation of SCN2A in mice, and with altered kinetics of SCN1A in human patients. Movement disorders including tremor, ataxia, dystonia and paralysis have been observed in mice with mutations of SCN8A. Electrophysiological recordings from neurons isolated from mice with mutations in individual channels reveal the contributions of each channel to in vivo firing patterns. In addition to monogenic disease, Na+ channel mutations are likely to contribute to polygenic disease susceptibility and to normal variation in neuronal function. Advances in molecular methods coupled with genomic sequences from the Human Genome Project will permit identification of many new patient mutations and generation of animal models to dissect their physiological and cellular consequences. PMID- 11771653 TI - Channelopathies: episodic disorders of the nervous system. AB - The field of channelopathies is a newly recognized group of disorders named after the site of their molecular defects--voltage- and ligand-gated ion channels. While voltage-gated ion channel mutants have been recognized for some time in organisms such as Drosophila, the first channelopathy in humans was reported within the last decade. The recognition of this group of disorders began with the definition of the molecular basis of a group of unusual muscle disorders called the periodic paralysis and non-dystrophic myotonias. Interestingly, this group of muscle disorders share some interesting phenotypic features with a number of seemingly disparate human diseases that involve not only skeletal muscle, but also brain and heart. Some similarities that exist among these different disorders include their episodic nature, similarities with regard to factors that precipitate attacks, therapeutic agents which can help to treat or prevent attacks, and in some cases, a degenerative component that arises in addition to the episodic attacks. The study of these diseases, along with the recognition of common clinical and pathophysiological themes among these disorders has led to tremendous growth in our understanding of these diseases and the hope of developing better therapies. PMID- 11771654 TI - Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. AB - Although low absolute values of bone mineral density (BMD) predict increased fracture risk in osteoporosis, it is not certain how well increases in BMD with antiresorptive therapy predict observed reductions in fracture risk. This work examines the relationships between changes in BMD after 1 year or 3 years of raloxifene or placebo therapy and the risk for new vertebral fractures at 3 years. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis were randomized to placebo or raloxifene 60 mg/day or 120 mg/day. Relationships between baseline BMD and changes in BMD from baseline with the risk of new vertebral fractures were analyzed in this cohort using logistic regression models with the raloxifene doses pooled. As has been observed in other populations, women with the lowest baseline lumbar spine or femoral neck BMD in the MORE cohort had the greatest risk for vertebral fractures. Furthermore, for any percentage change, either increase or decrease in femoral neck or lumbar spine BMD at 1 year or 3 years, raloxifene-treated patients had a statistically significantly lower vertebral fracture risk compared with placebo-treated patients. The decrease in fracture risk with raloxifene was similar across the range of percentage change in femoral neck BMD observed at 3 years; patients receiving raloxifene had a 36% lower risk of vertebral fracture compared with those receiving placebo. At any percentage change in femoral neck and lumbar spine BMD observed at 1 year, raloxifene treatment decreased the risks of new vertebral fractures at 3 years by 38% and 41%, respectively. The logistic regression model showed that the percentage changes in BMD with raloxifene treatment accounted for 4% of the observed vertebral fracture risk reduction, and the other 96% of the risk reduction remains unexplained. The present data show that the measured BMD changes observed with raloxifene therapy are poor predictors of vertebral fracture risk reduction with raloxifene therapy. PMID- 11771655 TI - Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. AB - Osteoblasts secrete a complex extracellular matrix (ECM) containing collagenous and noncollagenous proteins, bone morphogenetic proteins (BMPs), and growth factors. Osteoblast-specific gene expression requires ascorbic acid (AA) dependent assembly of a collagenous ECM. Matrix responsiveness requires an alpha2beta1 integrin-collagen interaction and mitogen-activated protein kinase (MAPK) activity, which phosphorylates and activates the osteoblast-specific transcription factor Cbfa1. This study examines interactions between this integrin/MAPK-mediated pathway and signals initiated by BMPs contained in the osteoblast matrix. MC3T3-E1 cells were shown to constitutively express BMP-2, BMP 4, and BMP-7. Noggin, a specific BMP inhibitor, reversibly blocked AA-induced gene expression, indicating that BMP production by MC3T3-E1 cells was necessary for differentiation. The ability of exogenously added BMP-2, BMP-4, or BMP-7 to stimulate osteocalcin (OCN) and bone sialoprotein (BSP) mRNAs or OCN promoter activity was synergistically increased in cells that were actively synthesizing an ECM (i.e., were grown in the presence of AA). A minimum of 4 days of ECM accumulation was required for this synergistic response to be observed. Neither BMP-7, AA, nor a combination of these two treatments had major effects on Cbfa1 messenger RNA (mRNA) or protein levels, as would be expected if regulation was mainly at the posttranscriptional level. U0126, a specific inhibitor of MAPK/extracellular signal-regulated kinase (MEK), blocked AA- or BMP-7/AA dependent gene expression in a time- and dose-dependent manner that was closely correlated with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation. This work establishes that autocrine BMP production as well as integrin-mediated cell-collagen interactions are both required for osteoblast differentiation, and both these pathways require MAP kinase activity. PMID- 11771656 TI - Bone turnover matters: the raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. PMID- 11771657 TI - Identification of the functional domain of osteoclast inhibitory peptide-1/hSca. AB - Osteoclast (OCL) activity is controlled by local factors produced in the bone microenvironment. We previously identified a novel inhibitor of OCL formation that is produced by OCLs (osteoclast inhibitory peptide-1/human Sca [OIP 1/hSca]). OIP-1/hSca is a glycosylphosphatidylinositol (GPI)-linked membrane protein (16 kDa) that is cleaved from the OCL surface. Immunocytochemical staining further confirmed the expression of OIP-1/hSca in OCL formed in mouse bone marrow cultures. However, the structure/function mechanisms responsible for the inhibitory effects of OIP-1/hSca on OCL formation are unknown. Therefore, we expressed deletion mutants of OIP-1 in 293 cells and tested their effects on OCL formation. These studies indicated that the carboxy-terminal peptide (c-peptide) region is critical for OIP-1/hSca activity. A 33 amino acid OIP-1 c-peptide (10 100 ng/ml) significantly inhibited 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced OCL formation and pit formation capacity of OCL on dentine slices in human bone marrow cultures. Furthermore, the c-peptide (10-100 ng/ml) significantly inhibited early human OCL precursor (granulocyte-macrophage colony-forming unit [GM-CFU]) colony formation in methylcellulose cultures. The polyclonal antibody against the OIP-1 c-peptide neutralized the inhibitory effect of OIP-1 c-peptide on OCL formation in mouse bone marrow cultures in vitro. These results show that the OIP-1 c-peptide is the functional domain of OIP-1 and that availability of neutralizing antibody specific to the OIP-1 c-peptide should provide important mechanistic insights into OIP-1/hSca inhibition of osteoclastogenesis in the bone microenvironment. PMID- 11771658 TI - Disruption of the p53 gene results in preserved trabecular bone mass and bone formation after mechanical unloading. AB - We tested the hypothesis that mechanical unloading facilitates signaling of p53, an important modulator of cell cycling and apoptosis, in bone marrow cells and thereby reduces trabecular bone volume (BV). We performed histomorphometric analyses and bone marrow cell cultures in tail-suspended (TS) p53 null (p53-/-) and wild-type (p53+/+) mice. Eight-week-old male mice were assigned to four groups after 1-week acclimatization: p53+/+ + ground control (GC), p53+/+ + TS, p53-/- + GC, and p53-/- + TS. Bilateral tibial samples were used for analysis. The histomorphometric parameters of trabecular structure, formation and resorption did not differ between the p53-/- + GC and p53+/+ + GC groups. Trabecular BV in p53+/+ + TS mice was significantly reduced to 45% of that in the p53+/+ + GC group after one week of TS. In contrast, BV in p53-/- + TS mice was preserved at the same level as that in the p53-/- + GC group. The bone formation rate (BFR) was significantly reduced in p53+/+ + TS but not in p53-/- + TS mice. Unloading significantly increased trabecular osteoclast number (Oc.N) and surface in p53+/+ + TS mice compared with the p53+/+ + GC group, but the difference was not significant between p53-/- + TS and p53-/- + GC mice. In bone marrow cell culture, the numbers of alkaline phosphatase-positive (ALP+) colony-forming units fibroblastic (CFU-f) and mineralized nodules were significantly reduced in p53+/+ + TS, but not p53-/- + TS mice. [3H]thymidine incorporation into bone marrow cells was higher in p53-/- mice than in p53+/+ mice, independent of mechanical loading or unloading. Flow cytometric cell cycle analysis revealed that unloading significantly increased the percentage of hypoploid bone marrow cells in p53+/+ mice relative to that in p53+/+ + GC mice, but there was no significant difference in ploidy between p53-/- + TS and p53-/- + GC mice. Expression levels of p53 and p21 mRNAs were enhanced after TS in bone marrow cells from p53+/+ mice. Our data show that trabecular bone mass and bone formation were preserved after tail-suspension in p53-/- mice, closely associated with ALP+ CFU-f and mineralized nodule formation in marrow cultures obtained from tibias of p53-/- mice. We speculate that bone loss due to mechanical unloading may be related to facilitation of intracellular p53-p21 signaling. PMID- 11771659 TI - Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. AB - Ossification of the posterior longitudinal ligament of the spine (OPLL) is the predominant myelopathy among Japanese, and is usually diagnosed by ectopic bone formation in the paravertebral ligament in Japanese and other Asians. To detect genetic determinants associated with OPLL, we performed an extensive nonparametric linkage study with 126 affected sib-pairs using markers for various candidate genes by distinct analyses, SIBPAL and GENEHUNTER. Eighty-eight candidate genes were selected by comparing the genes identified by complementary DNA (cDNA) microarray analysis of systematic gene expression profiles during osteoblastic differentiation of human mesenchymal stem cells with the genes known to be involved in bone metabolism. Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage (p = 0.016, nonparametric linkage [NPL] score = 1.83). Of 64 genes known to be associated with bone metabolism, 7 showed weak evidence of linkage by SIBPAL analysis (p < 0.05): cadherin 13 (CDH13), bone morphogenetic protein 4 (BMP4), proteoglycan 1 (PRG1), transforming growth factor beta 3 (TGFb3), osteopontin (OPN), parathyroid hormone receptor 1 (PTHR1), and insulin-like growth factor 1 (IGF1). Among these genes, BMP4 (NPL = 2.23), CDH13 (NPL = 2.00), TGFb3 (NPL = 1.30), OPN (NPL = 1.15), and PTHR1 (NPL = 1.00) showed evidence of linkage by GENEHUNTER. Only BMP4 reached criteria of suggestive evidence of linkage. Because this gene is a well-known factor in osteogenetic function, BMP4 should be screened in further study for the polymorphism responsible. PMID- 11771660 TI - Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine. AB - Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord. Based on the fact that the nucleotide pyrophosphatase (Npps) gene is responsible for ectopic ossification in ttw, an OPLL model mouse, the possibility was explored whether the human NPPS gene is associated with susceptibility to and severity of OPLL. First, we screened for single-nucleotide polymorphisms (SNPs) in the human NPPS locus using selected 25 OPLL patients with young onset (< 35 years old) or severe ossification (> 10 ossified vertebrae), and identified three novel SNPs in the locus. A case-control association study between 180 OPLL patients and 265 non OPLL controls showed that one of these SNPs, IVS15-14T --> C substitution, was more frequently observed in OPLL patients (p = 0.022), especially in those with severe ossification (p < 0.0001) and young onset (p = 0.002), than in controls. A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification. We conclude that the IVS15-14T --> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL. PMID- 11771661 TI - Sequence analysis of measles virus nucleocapsid transcripts in patients with Paget's disease. AB - It has been debated for almost 30 years whether Paget's disease of bone results from paramyxoviral infection of osteoclasts (OCs). Paramyxoviral-like nuclear inclusions are found in OCs from patients with Paget's disease, and measles virus (MV) or canine distemper virus (CDV) messenger RNA (mRNA) transcripts have been detected by in situ hybridization in bone cells from pagetic lesions. Furthermore, immunocytochemical studies have shown the presence of several paramyxoviral species in OCs from patients with Paget's disease. However, others have been unable to detect paramyxoviral transcripts in bone samples from patients with Paget's disease or marrow cultures from involved sites of patients with Paget's disease. Furthermore, no one has been able to isolate an infectious virus from pagetic bone samples or marrow cells from patients with Paget's disease, and a full-length viral gene has not been sequenced from pagetic samples. In this study, we have obtained the full-length sequence for the MV nucleocapsid (MVNP) gene in bone marrow from an involved site from a patient with Paget's disease and more than 700 base pairs (bps) of MVNP sequence in 3 other patients with Paget's disease. These sequences were undetectable in four normal marrow samples studied simultaneously. The sequences from the patients contained multiple mutations that differed from the Edmonston strain MVNP gene. These findings are consistent with the presence of a chronic MV infection in affected sites from these patients with Paget's disease. PMID- 11771662 TI - Use of type I collagen green fluorescent protein transgenes to identify subpopulations of cells at different stages of the osteoblast lineage. AB - Green fluorescent protein (GFP)-expressing transgenic mice were produced containing a 3.6-kilobase (kb; pOBCol3.6GFPtpz) and a 2.3-kb (pOBCol2.3GFPemd) rat type I collagen (Col1a1) promoter fragment. The 3.6-kb promoter directed strong expression of GFP messenger RNA (mRNA) to bone and isolated tail tendon and lower expression in nonosseous tissues. The 2.3-kb promoter expressed the GFP mRNA in the bone and tail tendon with no detectable mRNA elsewhere. The pattern of fluorescence was evaluated in differentiating calvarial cell (mouse calvarial osteoblast cell [mCOB]) and in marrow stromal cell (MSC) cultures derived from the transgenic mice. The pOBCol3.6GFPtpz-positive cells first appeared in spindle shaped cells before nodule formation and continued to show a strong signal in cells associated with bone nodules. pOBCol2.3GFPemd fluorescence first appeared in nodules undergoing mineralization. Histological analysis showed weaker pOBCol3.6GFPtpz-positive fibroblastic cells in the periosteal layer and strongly positive osteoblastic cells lining endosteal and trabecular surfaces. In contrast, a pOBCol2.3GFPemd signal was limited to osteoblasts and osteocytes without detectable signal in periosteal fibroblasts. These findings suggest that Col1a1GFP transgenes are marking different subpopulations of cells during differentiation of skeletal osteoprogenitors. With the use of other promoters and color isomers of GFP, it should be possible to develop experimental protocols that can reflect the heterogeneity of cell differentiation in intact bone. In primary culture, this approach will afford isolation of subpopulations of these cells for molecular and cellular analysis. PMID- 11771663 TI - Complex segregation analysis of the radiographic phalanges bone mineral density and their age-related changes. AB - The complex segregation analyses performed in our previous studies revealed a significant major gene (MG) effect on the age-adjusted cortical and cancellous bone mineral density (BMD) in two ethnically different populations, Chuvasha and Turkmenians. The aim of the present study was to test the hypothesis of pleiotropic MG control of three components of bone aging, that is, the baseline level of BMD (mu(gs)), the age at onset of the bone mass loss (T(gs)), and the rate of this loss over the years (alpha(gs)). Nuclear and more complex pedigrees from the same two ethnic samples were assessed for hand phalangeal BMD (Chuvasha, 1208 individuals, and Turkmenians, 643 individuals), and complex segregational analysis incorporating age and sex effects directly into MG penetrance function was carried out. The results of the present analysis clearly confirmed the existence of the putative MG and showed that the proportion of BMD variation attributable to this MG effect within the sex was remarkably similar in both populations and ranged between 34.7% and 35.2%. The most parsimonious model for BMD transmission in Chuvasha pedigrees additionally indicated significant residual correlation between siblings and clear sex differences in the annual rates of bone loss alpha(gs). The latter was more than twice as high in females than that in males (0.086 SD vs. 0.033 SD per year). In Turkmenian pedigrees the most parsimonious model presented obvious evidence of the MG control of BMD baseline levels in both sexes with significantly lower baseline levels and younger age at onset (T(gs)) in females. No clear MG effects were inferred on T(gs) and/or alpha(gs) in either sample, either in males or in females. That is, the present study does not suggest MG x SEX x AGE interaction. We suppose that if the rate of age-related changes in phalangeal BMD is genetically determined, then these are not the same genes as those affecting the BMD baseline levels. PMID- 11771664 TI - Bone strength at clinically relevant sites displays substantial heterogeneity and is best predicted from site-specific bone densitometry. AB - In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual-energy X-ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site-specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 +/- 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3-point-bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50-60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20-35% at distant sites, advocating a site-specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process. PMID- 11771665 TI - Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women. AB - Although median levels of bone turnover are increased in postmenopausal women, it is unclear whether the low circulating levels of endogenous estrogen exert a regulatory role on these levels. This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age +/- SD, 69 +/- 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months. Letrozole treatment reduced serum estrone (E1) and estradiol (E2) to near undetectable levels (p < 0.0001). This treatment did not affect bone formation markers but, as compared with the placebo group, increased bone resorption markers (urine 24-h pyridinoline [PYD] by 13.3% [p < 0.05] and 24-h urine deoxypyridinoline [DPD] by 14.2% [p < 0.05]) and decreased serum parathyroid hormone (PTH) by 22% (p = 0.002). These data indicate that in late postmenopausal women even the low serum estrogen levels present exert a restraining effect on bone turnover and support the concept that variations in these low levels may contribute to differences in their rate of bone loss. PMID- 11771666 TI - Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. AB - Expansile skeletal hyperphosphatasia (ESH) is a singular disorder characterized in the year 2000 in a mother and daughter with early-onset deafness, premature loss of teeth, progressive hyperostotic widening of long bones causing painful phalanges in the hands, accelerated bone remodeling, and episodic hypercalcemia likely inherited as a highly penetrant, autosomal dominant trait. Absence of large osteolytic lesions with cortical thinning in major long bones, together with bouts of hypercalcemia, indicated that ESH is not a variant of familial expansile osteolysis (FEO). Here, we investigated the molecular basis of ESH after three families with FEO were reported to have an identical 18-base pair tandem duplication (84dup18) in the signal peptide sequence of the TNFRSF11A gene that encodes receptor activator of nuclear factor-kappaB (RANK). We find that ESH is caused by a remarkably similar 15-base pair tandem duplication (84dup15) in TNFRSF11A. Hence, ESH and FEO are allelic diseases and ESH, like FEO, probably reflects increased activity in the skeleton of the RANK target, nuclear factor kappaB (NF-kappaB). PMID- 11771667 TI - Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. AB - Osteogenesis imperfecta (OI) is a heritable disease of bone in which the hallmark is bone fragility. Usually, the disorder is divided into four groups on clinical grounds. We previously described a group of patients initially classified with OI type IV who had a discrete phenotype including hyperplastic callus formation without evidence of mutations in type I collagen. We called that disease entity OI type V. In this study, we describe another group of 8 patients initially diagnosed with OI type IV who share unique, common characteristics. We propose to name this disorder "OI type VI." Fractures were first documented between 4 and 18 months of age. Patients with OI type VI sustained more frequent fractures than patients with OI type IV. Sclerae were white or faintly blue and dentinogenesis imperfecta was uniformly absent. All patients had vertebral compression fractures. No patients showed radiological signs of rickets. Lumbar spine areal bone mineral density (aBMD) was low and similar to age-matched patients with OI type IV. Serum alkaline phosphatase levels were elevated compared with age matched patients with type IV OI (409 +/- 145 U/liter vs. 295 +/- 95 U/liter; p < 0.03 by t-test). Other biochemical parameters of bone and mineral metabolism were within the reference range. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations, and type I collagen protein analyses were normal. Qualitative histology of iliac crest bone biopsy specimens showed an absence of the birefringent pattern of normal lamellar bone under polarized light, often with a "fish-scale" pattern. Quantitative histomorphometry revealed thin cortices, hyperosteoidosis, and a prolonged mineralization lag time in the presence of a decreased mineral apposition rate. We conclude that type VI OI is a moderate to severe form of brittle bone disease with accumulation of osteoid due to a mineralization defect, in the absence of a disturbance of mineral metabolism. The underlying genetic defect remains to be elucidated. PMID- 11771668 TI - Y-position collagen II mutation disrupts cartilage formation and skeletal development in a transgenic mouse model of spondyloepiphyseal dysplasia. AB - Mice were generated by pronuclear injection of a type II collagen transgene harboring an Arg789Cys (R789C) mutation that has been found in patients with spondyloepiphyseal dysplasia (SED). Expression was directed to cartilage by the murine Col2a1 promoter to examine the consequences of mutations involving the Y position of the collagen helix Gly-X-Y triplet on skeletogenesis. The transgenic mice had very short limbs, short trunk, short snout, and cleft palate; they died at birth. Their growth plates were disorganized and collagen fibrils were sparse in cartilage matrix. When the transgene was expressed in RCS cells, there was no evidence that R789C-bearing collagen chains were incorporated into stable collagen molecules. Molecular modeling of the mutation raised the possibility that it destabilizes the collagen triple helix. Together our results suggest that Y-position mutations, such as R789C, can act in a dominant negative manner to destabilize collagen molecules during assembly, reducing their availability to form fibrils, the deficiency of which profoundly disturbs the template functions of cartilage during skeletogenesis. PMID- 11771669 TI - Chondrogenic activity of the heparan sulfate proteoglycan perlecan maps to the N terminal domain I. AB - C3H10T1/2 cells differentiate along a chondrogenic pathway when plated onto the extracellular matrix (ECM) protein perlecan (Pln). To identify the region(s) within the large Pln molecule that provides a differentiation signal, recombinant Pln-sequence-based polypeptides representing distinct structural domains were assayed for their ability to promote chondrogenesis in C3H10T1/2 cells. Five distinct domains, along with structural variations, were tested. The N-terminal domain I was tested in two forms (IA and IB) that contain only heparan sulfate (HS) chains or both HS and chondroitin sulfate (CS) chains, respectively. A mutant form of domain I lacking attachment sites for both HS and CS (Pln I(mut)) was tested also. Other constructs consecutively designated Pln domains II, III(A C), IV(A,B), and V(A,B) were used to complete the structure-function analysis. Cells plated onto Pln IA or Pln IB but no other domain rapidly assembled into cellular aggregates of 40-120 microm on average. Aggregate formation was dependent on the presence of glycosaminoglycan (GAG) chains, because Pln I-based polypeptides lacking GAG chains either by enzymatic removal or mutation of HS/CS attachment sites were inactive. Aggregates formed on GAG-bearing Pln IA stained with Alcian Blue and were recognized by antibodies to collagen type II and aggrecan but were not recognized by an antibody to collagen type X, a marker of chondrocyte hypertrophy. Collectively, these studies indicate that the GAG bearing domain I of Pln provides a sufficient signal to trigger C3H10T1/2 cells to enter a chondrogenic differentiation pathway. Thus, this matrix proteoglycan (PG) found at sites of cartilage formation in vivo is likely to enhance early stage differentiation induced by soluble chondrogenic factors. PMID- 11771670 TI - Antiangiogenic treatment delays chondrocyte maturation and bone formation during limb skeletogenesis. AB - Hypertrophic chondrocytes have important roles in promoting invasion of cartilage by blood vessels and its replacement with bone. However, it is unclear whether blood vessels exert reciprocal positive influences on chondrocyte maturation and function. Therefore, we implanted beads containing the antiangiogenic molecule squalamine around humeral anlagen in chick embryo wing buds and monitored the effects over time. Fluorescence microscopy showed that the drug diffused from the beads and accumulated in humeral perichondrial tissues, indicating that these tissues were the predominant targets of drug action. Diaphyseal chondrocyte maturation was indeed delayed in squalamine-treated humeri, as indicated by reduced cell hypertrophy and expression of type X collagen, transferrin, and Indian hedgehog (Ihh). Although reduced in amount, Ihh maintained a striking distribution in treated and control humeri, being associated with diaphyseal chondrocytes as well as inner perichondrial layer. These decreases were accompanied by lack of cartilage invasion and tartrate-resistant acid phosphatase positive (TRAP+) cells and a significant longitudinal growth retardation. Recovery occurred at later developmental times, when in fact expression in treated humeri of markers such as matrix metalloproteinase 9 (MMP-9) and connective tissue growth factor (CTGF) appeared to exceed that in controls. Treating primary cultures of hypertrophic chondrocytes and osteoblasts with squalamine revealed no obvious changes in cell phenotype. These data provide evidence that perichondrial tissues and blood vessels in particular influence chondrocyte maturation in a positive manner and may cooperate with hypertrophic chondrocytes in dictating the normal pace and location of the transition from cartilage to bone. PMID- 11771671 TI - Matrix regulation of skeletal cell apoptosis II: role of Arg-Gly-Asp-containing peptides. AB - This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells. PMID- 11771672 TI - The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. AB - In this study we investigated the role of bone lining cells in the coordination of bone resorption and formation. Ultrastructural analysis of mouse long bones and calvariae revealed that bone lining cells enwrap and subsequently digest collagen fibrils protruding from Howship's lacunae that are left by osteoclasts. By using selective proteinase inhibitors we show that this digestion depends on matrix metalloproteinases and, to some extent, on serine proteinases. Autoradiography revealed that after the bone lining cells have finished cleaning, they deposit a thin layer of a collagenous matrix along the Howship's lacuna, in close association with an osteopontin-rich cement line. Collagenous matrix deposition was detected only in completely cleaned pits. In bone from pycnodysostotic patients and cathepsin K-deficient mice, conditions in which osteoclastic bone matrix digestion is greatly inhibited, bone matrix leftovers proved to be degraded by bone lining cells, thus indicating that the bone lining cell "rescues" bone remodeling in these anomalies. We conclude that removal of bone collagen left by osteoclasts in Howship's lacunae is an obligatory step in the link between bone resorption and formation, and that bone lining cells and matrix metalloproteinases are essential in this process. PMID- 11771673 TI - Effects of geranylgeranoic acid in bone: induction of osteoblast differentiation and inhibition of osteoclast formation. AB - Retinoids are known to be of special importance for normal bone growth and development. Recently, we reported that retinoids not only induced osteoblast differentiation, but also inhibited osteoclast formation in vitro. In this study, we examined the osteogenic effects of geranylgeranoic acid (GGA), a chemically synthesized acyclic retinoid, in bone in vitro and in vivo. GGA not only suppressed proliferation of osteoblastic MC3T3-E1 cells, but also up-regulated differentiation markers of osteoblasts such as alkaline phosphatase (ALP) activity and expression of osteopontin (OP) messenger RNA (mRNA). In contrast, GGA inhibited osteoclast formation induced by 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] in cocultures of mouse bone marrow cells and primary osteoblasts. Treatment of stromal ST2 cells with GGA restored the 1alpha,25(OH)2D3- or prostaglandin E2 (PGE2)-induced suppression of osteoprotegerin (OPG) mRNA expression. GGA inhibited osteoclast formation induced by macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) in the culture of bone marrow macrophages. Thus, it is likely that GGA inhibits osteoclast formation by affecting both osteoblasts and osteoclast progenitors in the coculture system. Furthermore, in vivo, GGA increased bone mineral density (BMD) of total as well as distal femur in a P6 strain of senescence-accelerated mice (SAMP6). These results indicate that GGA increases bone mass by maintaining a positive balance of bone turnover by inducing osteoblast differentiation and suppressing osteoclast formation. PMID- 11771674 TI - Biochemical functions of coenzyme Q10. AB - Coenzyme Q is well defined as a crucial component of the oxidative phosphorylation process in mitochondria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis. New roles for coenzyme Q in other cellular functions are only becoming recognized. The new aspects have developed from the recognition that coenzyme Q can undergo oxidation/reduction reactions in other cell membranes such as lysosomes. Golgi or plasma membranes. In mitochondria and lysosomes, coenzyme Q undergoes reduction/oxidation cycles during which it transfers protons across the membrane to form a proton gradient. The presence of high concentrations of quinol in all membranes provides a basis for antioxidant action either by direct reaction with radicals or by regeneration of tocopherol and ascorbate. Evidence for a function in redox control of cell signaling and gene expression is developing from studies on coenzyme Q stimulation of cell growth, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of membrane channels. Deficiency of coenzyme Q has been described based on failure of biosynthesis caused by gene mutation, inhibition of biosynthesis by HMG coA reductase inhibitors (statins) or for unknown reasons in ageing and cancer. Correction of deficiency requires supplementation with higher levels of coenzyme Q than are available in the diet. PMID- 11771675 TI - Eating patterns, dietary quality and obesity. AB - Obesity among children has reached epidemic proportions. Today, an estimated one in four children in the United States is overweight. while 11% arc obese. Children who are overweight tend to remain so up to 20 years of age; in general, they have a 1.5- to twofold higher risk for becoming overweight as adults. The prevalence of overweight has increased approximately twofold in the 20-year period from 1974 to 1994, with the largest increases observed among 19- to 24 year-olds. The annual increases in weight and obesity that occurred from 1983 to 1994 were 50% higher than those from 1973 to 1982. Overweight youth are 2.4 times as likely to have a high serum total cholesterol level, and 43.5 times as likely to have three cardiovascular risk factors. Although the total energy intake of children has remained the same, and the macronutrient density of the diet has changed, the percentage of energy from fat has decreased, while that from carbohydrates and protein has increased. Children have been consuming lower amounts of fats/oils, vegetables/soups, breads/grains, mixed meats, desserts, candy, and eggs. and increasing amounts of fruits/fruit juices, beverages. poultry, snacks, condiments, and cheese. Changes in specific eating patterns may explain the increase in adiposity among children; e.g., increases have occurred in the number of meals eaten at restaurants, food availability, portion sizes, snacking and meal-skipping. Successful prevention and treatment of obesity in childhood could reduce the adult incidence of cardiovascular disease. Because substantial weight loss is difficult to maintain, the prevention of obesity by promoting healthier lifestyles should be one of our highest priorities in the new millennium. PMID- 11771676 TI - Weight loss and body mass index as predictors of HIV disease progression to AIDS in adults. Aquitaine cohort, France, 1985-1997. AB - OBJECTIVE: To assess the performance of weight related nutritional markers (reported involuntary weight loss greater than 10%, measured weight loss and body mass index-BMI-) in predicting HIV disease progression. DESIGN: Multirisk cohort of HIV-1 infected patients. METHOD: The three nutritional variables were studied in Cox proportional hazard models as time dependant variables. RESULTS: The sample included 2376 subjects (median follow up: 43.1 months), of those 675 experienced an AIDS defining event. After adjustment for well known prognostic factors, the reported weight loss greater than 10% tripled the risk of progression to clinical AIDS (Hazard ratio [HR] 3.0. 95% confidence interval [CI] 2.5-3.7). For measured weight loss under 5%. between 5% and 10% and greater than 10% of baseline weight compared with no weight loss, hazard ratios were respectively 1.8 (CI 1.5-2.2), 2.6 (CI 2.1-3.2) and 5.1 (CI 4.1-6.4). The relative risks of AIDS were 1.7 (CI 1.3-2.2) for BMI between 17 kg/m2 and 18.5 kg/m2, 2.6 (CI 1.7-4.0) for BMI between 16 kg/m2 and 17 kg/m2 and 4.7 (CI 3.0 7.4) for BMI under 16 kg/m2. COMMENTS: Even a limited weight loss measured at a given time during follow up increases the risk of HIV progression; moreover, a simple cross-sectionnal measure of BMI has a good predictive value for subsequent development of clinical disease. PMID- 11771677 TI - Nutritional status of middle-aged Vietnamese in Ho Chi Minh City. AB - OBJECTIVE: To investigate the nutritional status of middle-aged Vietnamese in Ho Chi Minh City. METHODS: A cross-sectional survey in 300 Vietnamese aged 40 to 59 years (113 men, 187 women) was conducted in an urban, suburban and rural area of Ho Chi Minh City based on interviews that included a 24-hour dietary recall, food frequency questionnaire, and a short socioeconomic questionnaire. Anthropometry and blood pressure were measured, and blood was collected for serum protein and lipid analysis. RESULTS: A high prevalence of underweight (BMI < 18.5) was observed in the rural and suburban populations (35% and 23%, respectively), and overweight (BMI > or = 25) was observed in the urban population (18%). A high percentage of serum total cholesterol (TC) below 150 mg/dL was observed in the rural and suburban areas (43% and 37%, respectively). By contrast, the prevalence of TC above 220 mg/dL was twofold higher in the urban and suburban residents (13% and 12%, respectively) than in rural residents (6%). More than 80% of urban residents were of medium or high-income status, whereas 61% of suburban residents were of medium-income status and 66% of rural residents were of low-income status. CONCLUSIONS: The nutritional status of middle-aged Vietnamese in Ho Chi Minh City was characterized by undernutrition in 35% of the low-income population and by overnutrition in 18% the high-income population. Undenutrition was still a public health problem in the rural area whereas overnutrition started to become a noteworthy problem in the urban area. The suburban area suffered from both under- and overnutrition problems. Low lipid intake was the most important problem related to undernutrition in middle-aged residents of Ho Chi Minh City. PMID- 11771678 TI - Plasma-Saturating intakes of vitamin C confer maximal antioxidant protection to plasma. AB - OBJECTIVE: Supplemental vitamin C has been shown to reduce oxidative damage in vivo, yet the dose-response relationship between vitamin C intake and antioxidant protection is not known. This report examined blood indicators of oxidative stress in subjects consuming graded doses of vitamin C, from 75 to 2,000 mg/day. METHODS: Ten healthy, non-smoking men and women (26.1 +/- 2.1 years) were recruited from a campus population. During the ten-week study, subjects limited fruit and vegetable consumption (< or = 3 servings/day) and consumed a multivitamin and mineral pill daily. Beginning at week 3, subjects ingested either a vitamin C (n = 8) or placebo (n = 2) capsule, which were identical in appearance and taste. The content of the vitamin C capsule increased every two weeks (from 250 mg at weeks 3-4 to 500 mg, 1,000 mg. and 2,000 mg at weeks 5-6. 7 8. 9-10, respectively). Fasting blood samples were collected at two-week intervals and analyzed for vitamin C, total lipid hydroperoxides and Heinz bodies in packed erythrocytes incubated 24 hours at 37 degrees. RESULTS: Plasma vitamin C rose 55% in vitamin C-supplemented subjects by the end of the ten-week treatment (p < 0.05), and measures of oxidative stress decreased 60% to 90% (8.1 +/- 0.6 to 3.5 +/- 0.4 nmol/mL and 69.1 +/- 7.8% to 6.7 +/- 6.0% for total lipid hydroperoxides and Heinz bodies, respectively). Significant decreases in markers of oxidative stress were noted at the 500 mg, 1,000 mg and 2,000 mg dosages versus placebo. Antioxidant protection was similar at the 1,000 mg and 2,000 mg dosage. CONCLUSIONS: These data indicate that the antioxidant protection afforded by short-term vitamin C supplementation is maximal at the 500-1,000 mg dosage range. PMID- 11771679 TI - Alpha tocopheryl succinate, retinoic acid and polar carotenoids enhanced the growth-inhibitory effect of a cholesterol-lowering drug on immortalized and transformed nerve cells in culture. AB - OBJECTIVE: Statins (cholesterol lowering drugs) with a closed-ring structure (lovastatin, simvastatin and mevastatin) and an open-ring structure (pravastatin and fluvastatin) are currently used in the management of cardiac disease. Lovastatin and simvastatin inhibit the growth of tumor cells; however, the studies on the effect of a statin in combination with micronutrients such as alpha-tocopheryl succinate (alpha-TS), 13-cis retinoic acid (RA) and polar carotenoids (PC) have never been performed. The primary objective of this study was to investigate the effect of mevastatin alone and in combination with the above micronutrients on the growth of mouse neuroblastoma (NB) cells and rat immortalized dopamine (DA) neurons in culture. In addition, a comparative efficacy of mevastatin and pravastatin on the growth of NB cells was studied. METHODS: Cells were treated with mevastatin in combination with individual antioxidants, alpha-TS, RA and polar carotenoids, 24 hours after plating. Fresh growth medium and agents were changed at two days after treatment, and the viability in control and experimental groups was determined at three days after treatment by MTT assay. Each experiment was repeated three times with triplicate samples per treatment. Growth in experimental groups was expressed as % of untreated cells. RESULTS: Mevastatin inhibited the growth of neuroblastoma (NB) cells and immortalized, non-tumorigenic dopamine (DA) neurons in culture in a dose-dependent manner. Immortalized DA neurons were more sensitive to mevastatin than NB cells. Pravastatin at similar concentrations was ineffective in inhibiting the growth of NB cells. Mevastatin in combination with alpha-TS, RA or PC was more effective in reducing the growth of NB and DA neurons than the individual agents. CONCLUSIONS: Statins with a closed-ring structure can inhibit the growth of established cancer cells as well as immortalized cells (equivalent to pre-malignant lesion), whereas statins with an open-ring structure may be ineffective. A combination of a statin having a closed-ring structure with alpha TS, RA and PC may be one of the potentially useful anti-cancer agents for prevention and treatment strategies. PMID- 11771680 TI - Acute nutritional and intestinal changes after pelvic radiation. AB - OBJECTIVE: Pelvic radiotherapy induces acute small bowel injury but its effects on nutritional status are unknown. The objective of this study was to prospectively evaluate nutritional, functional and morphologic intestinal changes, after radiotherapy. METHODS: Fifteen patients were studied before and after pelvic irradiation. A clinical, nutritional and routine clinical laboratory assessment was performed. Nutritional parameters included dietary recall, subjective global assessment, anthropometric measurements (body mass index, skinfold thickness at four sites and circumferences of arm, waist and hip), hand grip strength, indirect calorimetry and Dual Energy X-ray absortiometry (DEXA). Intestinal parameters included permeabilty to sugars (assessed by lactulose and mannitol urinary excretion), intestinal transit time (measured by hydrogen breath test after ingestion of lactulose) and jejunal biopsies. RESULTS: Thirteen patients presented diarrhea during radiation therapy. After five weeks, intestinal permeability increased, while intestinal transit time decreased. The second biopsy showed hypertrophy of villae and crypts. Simultaneously, patients lost weight at the expense of fat free mass. Resting energy expenditure was elevated prior to treatment and declined after five weeks. Changes in caloric ingestion were not significant. CONCLUSIONS: Our results indicate that pelvic radiation induces a loss of fat free mass along with intestinal morphologic and functional changes. PMID- 11771681 TI - Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men. AB - OBJECTIVE: Six lean (BMI = 20.8 +/- 0.7) and seven overweight (BMI = 30.8 +/- 1.7) young men (18-27 years old) were studied to investigate the acute effect of a high-carbohydrate meal on leptin levels and its relation to energy expenditure as well as to protein, carbohydrate and fat oxidation. METHODS: Study participants were given a high-carbohydrate meal (17% as protein, 80% as carbohydrates and 3% as lipids) covering 40% of their estimated daily energy requirements. Serum leptin. insulin. glucose, free fatty acids and triglycerides levels were measured before meal intake and during the frour postprandial hours. Furthermore, energy expenditure (EE), protein, carbohydrate and lipid oxidation were measured in fasted and fed conditions. RESULTS: Fasting leptin was found to be positively correlated with circulating insulin concentrations (r = .748; p = 0.011) and body fat in kg (r = .827; p = 0.001). During the measured postprandial period no statistically significant changes were found in leptin levels as compared with pre-meal values in either lean or overweight men, nor differences in leptin changes between both groups. After load intake, carbohydrate oxidation was lower in overweight individuals (p < 0.05). while no significant differences were observed in protein oxidation. Cumulative lipid oxidation was found to be negatively associated with post-meal leptin values, being significantly lower in the overweight as compared with lean men (p < 0.05). This study demonstrates that the acute postprandial fuel substrate utilization is altered in overweight men with a lower carbohydrate oxidation and a strong inhibition of lipid oxidation, which could be attributed to some leptin resistance. CONCLUSION: These data also suggest that short-term meal-related metabolic responses may explain the long term body adiposity if they are sustained over long intervals. PMID- 11771682 TI - Dietary fiber and lifestyle influence serum lipids in free living adult men. AB - OBJECTIVE: The aim of this study was to determine the effect of dietary fiber consumption and lifestyle on serum lipids in adult men with non-restricted diet and physical activity. METHODS: Two groups of 19 men were classified as high (48 g/day) and low fiber groups (27 g/day). Anthropometry, food frequency, daily weighed intakes and physical activity were done for a seven-day period. Fasting blood was collected and serum was analyzed for triglycerides, total cholesterol and lipoprotein cholesterol fractions. RESULTS: Crude correlation coefficients showed that total cholesterol was negatively associated with physical activity, total dietary fiber and P/S ratio (r = 0.52; p < 0.001. r = -0.44; p < 0.01, r = 0.51, p < 0.001). LDL-C was also correlated negatively with total dietary fiber and P/S ratio (r = -0.34, p < 0.03; r = -0.53, p < 0.01). It was also positively associated with dietary cholesterol and body weight (r = 0.34, p < 0.03; r = 0.31, p < 0.05). Serum triglycerides had an inverse association with total dietary fiber and physical activity (r = -0.30: p < 0.05; r = -0.45, p < 0.004). After controlling for energy intake, total fat, saturated fat, dietary cholesterol, physical activity and body mass index, LDL-C/HDL-C, and TC/HDL-C, remained significantly associated with dietary fiber (r = 0.34; p < 0.05 and r = 0.38; p < 0.02, respectively). CONCLUSIONS: This study provides evidence in free living men that there is an association between dietary fiber intake and favorable lipid status and that lifestyle defined by socioeconomic status, physical activity and the quality of the dietary fat intake can play an important role. Public health nutrition advice and policy should continue to emphasize the importance of these factors. PMID- 11771683 TI - Effect of copper on the localized corrosion resistance of Ni-Ti shape memory alloy. AB - An electrochemical study aiming at the evaluation of corrosion parameters using potentiodynamic and potentiostatic techniques ("scratch" and modified ASTM F746) was conducted in 0.9% NaCl on wires from equiatomic Ni-Ti and ternary Ni44Ti51Cu5 superelastic alloys with Ti90Mo10 as a reference material. The results obtained using potentiostatic tests, that simulate better the behavior of material in service conditions than potentiodynamic ones, indicate that both Ni-Ti and Ni-Ti Cu wires exhibit low corrosion potentials (approximately 50-150 mV versus SCE) inferior to that of Ti-Mo alloy. The latter proved to be immune to localized corrosion attacks up to 800 mV. PMID- 11771684 TI - Behaviour of nitinol in osteoblast-like ROS-17 cell cultures. AB - Nickel titanium shape memory metal alloy Nitinol (NiTi) has been used in dental wares and in gastrointestinal surgery. Nitinol is a promising implant material in orthopedics, but its biocompatibility, especially in long-term implantation is not confirmed yet. We studied Nitinol's effect on a cell culture model. Comparisons to stainless steel, pure titanium and pure nickel were performed. The effects of Nitinol on cell death rate, the apoptosis rate and the formation of local contacts were studied on rat osteosarcoma cell line ROS-17 in 48-h cultures. The cell death rate was assessed with combined calcein-ethidium homodimer labelling. The amount of dead cells 1000 cells were as follows: four in the NiTi, 21 in the Stst, 4.8 in the Ti and 51 in the Ni group. In the NiTi and Ti groups, the number of dead cells was significantly lower (p < or = 0.01) than in Ni group. The rate of apoptosis was detected with TUNEL-assay. The assay results were: 1.93 apoptotic cells 1000 cells in the NiTi, 1.1 in the Stst, 2.98 in the Ti and 0.62 in the Ni group. A comparison of these two results shows that 48% of the dead cells were apoptotic in the NiTi, 56.6 in the Stst, 62% in the Ti and only 1.8% in the Ni group. The focal contacts were stained with a paxillin antibody and counted. There were marked differences in the number of focal contacts per unit area compared to NiTi (774 focal contacts): 335 in Stst (p < or = 0.01), 462 in Ti (p < or = 0.01) and 261 in Ni (p < or = 0.005). Our results show that NiTi is well tolerated by the osteoblastic type ROS-17 cells. PMID- 11771685 TI - Influence of the charge of low molecular weight proteins on their efficacy of filtration and/or adsorption on dialysis membranes with different intrinsic properties. AB - Hemodialysis membranes eliminate by filtration low-molecular-weight toxic metabolites (urea and creatinine) with minimum interactions between blood components and the membrane itself. However, the ability of a membrane to adsorb specific proteins could be beneficial if the accumulation of these same proteins is implicated in the genesis of a pathological condition. Beta-amyloidosis which accompanies the elevation of beta2-microglobulin (11.8 kDa) in the plasma of dialysed patients is one such condition (Biochem. Biophys. Res. Commun. 129 (3) (1985) 701-706: Lancet 1 (1986) 1240-1311). To determine whether increases in plasma beta2-microglobulin levels were due to differences in filtration efficacy of the membrane used and/or to certain characteristics of this protein, e.g. its charge (pI 5.7) the adsorption and filtration of [3H] beta2-microglobulin and [3H] lysozyme of similar MW 14.5 kDa, but pI: 10.8 were compared on different membranes. It was found that, neither [3H] beta2-microglobulin nor [3H] lysozyme are removed by cuprophan, whereas over 75% of beta2-microglobulin is removed by filtration on polyacrylonitrile, polyacrylonitrile-polyethyleneimine, polysulfone and >95% by adsorption to polymethylmethacrylate-BK. For lysozyme, removal by adsorption is >95% on polyacrylonitrile and polyacrylonitrile-polyethyleneimine, 72% on polymethylmethacrylate-BK and by filtration is 95% on polysulfone. Hemodialysis membranes must therefore not simply be considered as filters of low molecular-weight metabolites but should be equally assessed for their capacity to eliminate potentially deleterious low-molecular-weight plasma proteins. PMID- 11771686 TI - Influence of pH and oxygen on copper corrosion in simulated uterine fluid. AB - This paper studies the copper corrosion in simulated uterine fluids in the presence of urea and/or albumin, at pH 5.0, 6.3 and 8.0, with 0.10, 0.15 and 0.20 atmospheres of oxygen pressure and without additional oxygen pressure, at 37 degrees C temperature, and for 1, 3, 7, 15, 21 and 30 days experimentation. The copper dissolution rate was determined using absorbance measurements. Copper dissolution was the highest at pH 8.0 and 0.20 atmospheres of oxygen pressure, 674 microg d(-1) for 1 day and 109 microg d(-1) for 30 days. The presence of albumin, contrary to urea, accelerates copper corrosion. PMID- 11771687 TI - Cytocompatibility study of organic matrix extracted from Caribbean coral porites astroides. AB - Since 1980, natural coral exoskeleton has been widely used as bone graft substitute. Despite numerous in vitro and in vivo studies. there is still a lack of knowledge concerning the organic matrix associated with coral exoskeleton (COM). In fact, some surgical interventions have failed and this has sometimes been attributed to the exoskeleton organic matrix. For others, only amino acids are present in the matrix after coral preparation for clinical use. The objective of this study was to extract the exoskeleton organic matrix to carry out biochemical analysis and study its specific cytocompatibility. Demineralized bone powder (DBP) was used as control. A decalcification process was used to extract COM and DBP. Protein, carbohydrate and glycosaminoglycan analysis was carried out in DBP and COM using classical staining methods. Human bone marrow cells were cultured in the presence of 20, 40, 80, 160 microg of COM or DBP for 24, 48 and 72 h. The methods used to analyze COM and DBP effects were scanning electron microscopy immunocytochemistry, manual cell count, and cyto-compatibility assay (Neutral red and MTT tests). Results showed that in spite of treating coral before clinical use, a COM was present in which GAG, protein and carbohydrate were found. The in vitro cytocompatibility of COM was confirmed for 20 and 40 microg values but was less pronounced for 80 and 160 microg levels. PMID- 11771688 TI - Initial attachment of osteoblasts to an optimised HAPEX topography. AB - The interactions between an implant material and the surrounding tissue are of a complicated nature, and the initial attachment of cells to the surface is important in determining the implant success. HAPEX has been developed as a second-generation orthopaedic biomaterial, with both mechanical and biological characteristics that make it suitable for bone augmentation. Further optimisation of the material is being continued to increase the attachment of osteoblasts coupled with improving mechanical characteristics, so it may be used in load bearing applications. It has been previously observed that polishing followed by roughening the surface of HAPEX enhances osteoblast proliferation and phenotype. This article discusses the recruitment of primary human osteoblast cells onto the optimised surface, by examining morphology and cytoskeletal changes using scanning electron microscopy and confocal laser scanning microscopy. The results show that the cells attach in greater numbers to the optimised surface, and develop notably faster, than cells on machined HAPEX. PMID- 11771689 TI - Sol-gel hydroxyapatite coatings on stainless steel substrates. AB - Thin film hydroxyapatite deposits onto sandblasted 316L stainless steel substrates were prepared using water-based sol-gel technique recently developed in our lab. The coatings were annealed in air at 375 degrees C, 400 degrees C, and 500 degrees C. Phase formation, surface morphology, interfacial microstructure, and interfacial bonding strength of the coatings were investigated. Apatitic structure developed within the coatings while annealing at temperatures > or = 400 degrees C, while those heat-treated at 375 degrees C showed poor crystallinity. The coatings were dense and firmly attached to the underlying substrates, reaching an average bonding strength (as determined through the pull-out test) of 44 MPa. Nano-porous structure was found for the coatings annealed at 500 degrees C, believed to result from grain growth, and causing a slight decrease in the bonding strength. Surface microcracking, although not extensive, occurred after annealing at temperatures > or = 400 degrees C, and was linked to non-uniform thickness of the coating due to roughness of the substrate. A contraction of the coatings as a result of sintering, and phase transition from amorphous (or poor crystalline) to reasonably good crystalline apatite, may be responsible for the loss of structural integrity of the thicker sections of the coatings. It seems quite promising that a dense and adhesive apatite coating can be achieved through water based sol gel technology after short-term annealing at around 400 degrees C in air. PMID- 11771690 TI - Mechanochemical-hydrothermal synthesis of carbonated apatite powders at room temperature. AB - Crystalline carbonate- and sodium-and-carbonate-substituted hydroxyapatite (CO3HAp and NaCO3HAp) powders were prepared at room temperature via a heterogeneous reaction between Ca(OH)2/CaCO3/Na2CO3 and (NH4)2HPO4 aqueous solution using the mechanochemical hydrothermal route. X-ray diffraction, infrared spectroscopy, thermogravimetry, and chemical analysis were performed. Room temperature products were phase-pure CO3HAp and NaCO3HAp containing 0.8-12 wt% of carbonate ions in the lattice. Dynamic light scattering revealed that the median agglomerate size of the room temperature CO3HAp and NaCO3HAp powders was in the range of 0.35-1.6 microm with a specific surface area between 82 and 121 m2/g. Scanning and transmission electron microscopy confirmed that the carbonated HAp powders consisted of mostly submicron aggregates of nanosized, approximately 20 nm crystals. The synthesized carbonated apatite powders exhibit chemical compositions and crystallinities similar to those of mineral constituents of hard tissues and therefore are promising for fabrication of bone-resembling implants. PMID- 11771691 TI - Effect of the substitution of M2O3 (M = La, Y, In, Ga, Al) for CaO on the bioactivity of 2.5CaO x 2SiO2 glass. AB - Glasses were prepared whose compositions are defined by the following general formula: (2.5 - x)CaO x x/3M2O3 x 2SiO2 (0 < or = x < or = 0.6) (M = Ga, Al, In). Their bioactivity was studied "in vitro" by soaking the glasses in a simulated body fluid (SBF). The consequent formation of calcium phosphate layer was studied by means of electron microscopy (EM) equipped with an energy-dispersive system (EDS) for elemental analysis and Infrared (IR) spectroscopy. The results are compared to the literature relative to the substitution of La2O3 and Y2O3 for CaO. It is observed that, in general, the substitution of M2O3 for CaO in the binary CaO-SiO2 glass composition progressively reduces the ability to form a calcium phosphate layer on the surfaces exposed to simulated body fluid (SBF). The composition limit can be related to the ionic field strength of the substituting cation and to the CaO content of the base glass. According to the mechanism reported in the literature a silica gel-like surface layer initially forms on the surfaces exposed to SBF. The observed results can be attributed to the effect of the substitution of M2O3 for CaO on the acidic properties of the silanolic groups. PMID- 11771692 TI - Gradient crosslinking of UHMWPE using irradiation in molten state for total joint arthroplasty. AB - Increased crosslink density increases the wear resistance of ultra-high molecular weight polyethylene (UHMWPE) acetabular components used in total hip reconstructions. However, increasing crosslink density can reduce the mechanical properties of UHMWPE. Other researchers have tried to limit the crosslinking to a superficial layer on the articulating surfaces to retain the properties of the virgin polymer. We present here a method of producing a gradient of crosslink density across the acetabular component. Acetabular liners with 26 mm inner diameter were machined from the UHMWPE. The liners were then irradiated at 140 degrees C in the molten state of the polymer using a 2 MeV electron beam with limited penetration of the effects of radiation into polyethylene. The liners were then machined to an inner diameter of 32 mm to remove the radiation induced oxidized surface layer. The limited penetration of the e-beam resulted in a gradient of crosslink density with a crosslink density of 0.15 +/- 0.01 mol/dm3 near the articulating surfaces and 0.12 +/- 0.01 mol/dm3 near the backside. The concentration of the trans-vinylene unsaturations decreased gradually as a function of depth from the articulating surfaces to the backside of the liners. The wear resistance of the melt-irradiated liners was contrasted with those of conventional liners using the Boston hip simulator. The gravimetric wear rate was 27 +/- 5 mg million cycles with the conventional liners, while the melt irradiated acetabular liners did not show any weight loss. PMID- 11771693 TI - The ultrastructure of the plasma-sprayed hydroxyapatite-bone interface predisposing to bone bonding. AB - The deposition of biological apatite and subsequent formation of bone on hydroxyapatite implants depends on the partial dissolution of the implant surface and the reprecipitation of carbonated apatite from the biological milieu. Previous investigations in vitro have shown that the degree of dissolution and reprecipitation decreases as the coating crystallinity increases. These findings prompted the current study of the effects of coating crystallinity on the mechanism of bone bonding. The process of mineralization of bone associated with a hydroxyapatite coating was compared to the normal process of ossification. Plasma-sprayed hydroxyapatite (PSHA) coated titanium alloy (6% Al-4% V) rods as received and annealed for 0.7 h at 600 degrees C in air to increase the coating crystallinity were implanted in the proximal and distal femora and proximal tibiae of adult mongrel dogs for 3 h, 3 and 10 days. Bony sites containing the implant were prepared for ultramicrotomy and transmission electron microscopy using an anhydrous embedding procedure: fixation in ethylene glycol and embedment in Spurr's resin. The results demonstrated the precipitation of biological apatite crystallites on non-annealed PSHA coatings in vivo within 3 h of implantation. After 3 and 10 days there were differences in the ultrastructure of the mineral phase on the surfaces of non-annealed and annealed surfaces. Observations showed that there was little difference in the mechanism of mineralization of bone associated with HA-coated prostheses and the normal process of ossification. PMID- 11771694 TI - Dissolution rates of carbonated hydroxyapatite in hydrochloric acid. AB - Osteoclasts have been shown to dissolve efficiently and effectively the mineral phase of bone by locally controlling the environment surrounding the cell. Although this mineral phase has been identified and well characterized as carbonated hydroxyapatite, there is little understanding of the factors that affect the dissolution properties of this mineral phase. Mimicking the mechanism by which osteoclasts dissolve the mineral phase of bone may provide insight into methods for the decalcification of atherosclerotic mineral deposits in the vascular system. Accordingly, a detailed characterization of the effects of various chemical and mechanical parameters on the dissolution of carbonated hydroxyapatite mineral was investigated in this study. Increases in the mineral dissolution rate (2-10 times) were associated with increases in dissolving solution [H+], osmolality, temperature, and flow rate. Mineral dissolution rate increases (5-8 times) were associated with greater surface area of the mineral and mechanical agitation of the dissolving solution. PMID- 11771695 TI - Measurements of the solubilities and dissolution rates of several hydroxyapatites. AB - Calcium phosphate based materials, such as apatites, are increasingly being developed and used in implants for orthopedic and dental applications. Previous investigation of various calcium phosphate ceramics has demonstrated great variability in the solubility characteristics in solution between materials with similar stoichiometric composition. Therefore, in this study, the solubility and rate of dissolution of three apatite sources, BoneSource, Norian cranial repair system (CRS), and a sintered hydroxyapatite (Calcitite) are evaluated in a thermodynamically closed system. The measured solubility under physiological conditions (tris buffer solution, pH 7.4, 37 degrees C) of BoneSource, Norian CRS and Calcitite is 7.5, 7.4 and 1.4 ppm, respectively. Initial dissolution rates at 10 min of BoneSource, CRS, and Calcitite were 0.0465, 0.1589, and essentially 0 mg/min respectively. Solubility product constants at 37 degrees C were calculated to be 1.49 x 10(-35) for CRS, 1.19 x 10(-35) for BoneSource, and 2.92 x 10(-42) for Calcitite. The increased solubility of the BoneSource and Norian CRS materials over that of Calcitite is related to their poor crystallinity compared to sintered hydroxyapatite. PMID- 11771696 TI - Platelet adhesion and activation on a shielded plasma gradient prepared on polyethylene. AB - Contact of blood with foreign materials evokes thrombogenic effects to an extent determined partly by the wettability of the biomaterials surface. Tools to study blood response towards a variation in materials wettability with minimal variation in chemistry are "gradient surfaces". However, most gradients have been prepared by diffusion or density immersion techniques, which results in a limited gradient range. Through glow discharge with partial shielding, gradients on polymers were prepared over a length of 5 cm, which facilitated studies to platelet adhesion on separate gradient sections. On polyethylene, advancing water contact angles varied from 90 degrees to 40 degrees, with a hysteresis of 30 degrees. ESCA indicated an increasing incorporation of oxygen towards the hydrophilic end. To examine the role of materials wettability on the activation of adhering platelets, sections of shielded plasma gradients were incubated in anticoagulated whole human blood. Fewer platelets adhered to the hydrophobic end, but those platelets were more activated than those on the hydrophilic end, as judged from their morphology and exposure of GpIIb-IIIa complex. However, partly related to the increased binding of platelets, the clotting activation after platelet deposition was highest on the hydrophilic end. Concluding, this new technique results in a large gradient range, which facilitates studies of formed blood elements in relation to the wettability. Platelets are more activated on hydrophobic polyethylene, while on moderate hydrophilic polyethylene more platelet adhesion and activation of the clotting system occurs. PMID- 11771697 TI - Adhesion, cytoskeletal architecture and activation status of primary human macrophages on a diamond-like carbon coated surface. AB - Diamond-like carbon is a promising surface coating for biomedicinal implants like coronary stents or hip joints. Before widespread clinical use of this material, its biocompatibility has to be thoroughly assessed. Cells likely to encounter a diamond-like coated implant in the human body are cells of the monocytic lineage. Their interaction with the diamond-like carbon coated surface will probably critically influence the fate of the implant, as monocytes orchestrate inflammatory reactions and also affect osseointegration of implants. We therefore investigated adhesion, cytoarchitecture and activation status of primary human monocytes and their differentiated derivatives, macrophages, on diamond-like coated glass coverslips using immunofluorescence technique. We show that adhesion of primary monocytes to a diamond-like-coated coverslip is slightly, but not significantly, enhanced in comparison to uncoated coverslips, while the actin and microtubule cytoskeletons of mature macrophages show a normal development. The activation status of macrophages, as judged by polarization of the cell body, was not affected by growth on a diamond-like carbon surface. We conclude that diamond like carbon shows good indications for biocompatibility to blood monocytes in vitro. It is therefore unlikely that contact with a diamond-like carbon coated surface in the human body will elicit inflammatory signals by these cells. PMID- 11771698 TI - Reactive coupling of poly(ethylene glycol) on electroactive polyaniline films for reduction in protein adsorption and platelet adhesion. AB - Poly(ethylene glycol) (PEG)-coupled polyaniline (PANI) film surfaces were prepared by incorporating the chlorinie end-capped methoxy PEG (mPEGCl) of molecular weight of about 2000 onto the emeraldine (EM) base form of PANI via N alkylation. The microstructure and composition of the mPEG-coupled PANI (mPEG-c PANI) surfaces were characterized by atomic force microscopy, contact angle measurement and X-ray photoelectron spectroscopy. The concentration of surface coupled mPEG increased with the increase in concentration of the mPEGCl solution. The mPEG-c-PANI film surfaces exhibited enhanced ability to repel protein adsorption, with only an moderate reduction in their electrical conductivity. The mPEG-c-PANI surface with a high concentration of coupled mPEG also exhibited good resistance towards platelet adhesion. PMID- 11771699 TI - Biostability of micro-photodiode arrays for subretinal implantation. AB - Micro-photodiode arrays based on semiconductor chip technology are being developed to replace degenerated photoreceptor cells in the retina. Electric current is generated in tiny micro-photodiodes and delivered to the adjacent tissue by micro-electrodes. One of the main requirements of a sub-retinal implantable device is long-term stability versus corrosion in vivo (biostability). Biostability of micro-photodiode arrays (MPDA) was investigated in vitro and in vivo. No significant damage was found on chips immersed for up to 21 months in saline solution. Under in vivo conditions, however, the silicon oxide passivation layer of the chip was dissolved within a period of about 6-12 months. Subsequently, the underlying silicon was corroded. In contrast, stimulation electrodes consisting of titanium nitride were well preserved both in vitro and in vivo. The deterioration of the electrical properties of the micro photodiodes correlated with the morphological damage observed. Strategies aiming at the development of an improved biostable encapsulation of neurotechnological implants have to be investigated and will be discussed briefly. PMID- 11771700 TI - Advanced technique for long term culture of epithelia in a continuous luminal basal medium gradient. AB - The majority of epithelia in our organism perform barrier functions on being exposed to different fluids at the luminal and basal sides. To simulate this natural situation under in vitro conditions for biomaterial testing and tissue engineering the epithelia have to withstand mechanical and fluid stress over a prolonged period of time. Leakage, edge damage and pressure differences in the culture system have to be avoided so that the epithelial barrier function is maintained. Besides, the environmental influences on important cell biological features such as, sealing or transport functions, have to remain upregulated and a loss of characteristics by dedifferentiation is prevented. Our aim is to expose embryonic renal collecting duct (CD) epithelia as model tissue for 14 days to fluid gradients and to monitor the development of tissue-specific features. For these experiments, cultured embryonic epithelia are placed in tissue carriers and in gradient containers, where different media are superfused at the luminal and basal sides. Epithelia growing on the tissue carriers act as a physiological barrier during the whole culture period. To avoid mechanical damage of the tissue and to suppress fluid pressure differences between the luminal and basal compartments improved transport of the medium and an elimination of unilaterally accumulated gas bubbles in the gradient container compartments by newly developed gas expander modules is introduced. By the application of these tools the yield of embryonic renal collecting duct epithelia with intact barrier function on a fragile natural support material could be increased significantly as compared to earlier experiments. Epithelia treated with a luminal NaCl load ranging from 3 to 24 mmol l were analyzed by immunohistochemical methods to determine the degree of differentiation. The tissue showed an upregulation of individual CD cell features as compared to embryonic epithelia in the neonatal kidney. PMID- 11771701 TI - Preparation and characterization of keratin-chitosan composite film. AB - Keratin-chitosan composite film was prepared by casting the mixed solution of both biopolymers in 75% acetic acid. Although keratin film without any additive is very fragile, 10-30 wt% of chitosan addition gave strong and flexible film (ultimate strength: 27-34 MPa, ultimate elongation: 4-9%). Glycerol (20 wt%) also afforded flexibility to keratin film (ultimate strength: 1 MPa, ultimate elongation: 28%). Further addition of chitosan to glycerol-containing keratin film increased the ultimate strength to 9-14 MPa but gave little effect on ultimate elongation. These data suggest that mechanical properties of keratin film are adjustable by appropriately adding chitosan and glycerol. Waterproof characteristics such as swelling behavior and mechanical properties after swelling were much ameliorated for the composite film compared with keratin and chitosan films, respectively. Furthermore, keratin-chitosan composite film as well as chitosan film decreased bacteria number when the bacteria suspension was treated with a film owing to the irreversible adsorption of bacteria onto the film. The composite film as well as keratin and chitosan films supported fibroblast attachment and proliferation, demonstrating to be a good substrate for mammalian cell culture. PMID- 11771702 TI - Mechanism of bonelike apatite formation on bioactive tantalum metal in a simulated body fluid. AB - Development of tantalum metal with bone-bonding ability is paid much attention because of its attractive features such as high fracture toughness, high workability and its achievement on clinical usage. Formation of bonelike apatite is an essential prerequisite for artificial materials to make direct bond to living bone. The apatite formation can be assessed in vitro using a simulated body fluid (SBF) that has almost equal compositions of inorganic ions to human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously forms the apatite after a long soaking period. The purpose of the present study is to clarify the reason why the NaOH and heat treatments accelerate the apatite formation on tantalum metal. X-ray photoelectron spectroscopy was used to analyze changes in surface structure of the tantalum metal at an initial stage after immersion in SBF. Untreated tantalum metal had tantalum oxide passive layer on its surface, while amorphous sodium tantalate was formed on the surface of the tantalum metal by the NaOH and heat treatments. After soaking in SBF, the untreated tantalum metal sluggishly formed small amount of Ta-OH groups by a hydration of the tantalum oxide passive layer on its surface. In contrast, the treated tantalum metal rapidly formed Ta-OH groups by exchange of Na+ ion in the amorphous sodium tantalate on its surface with H3O+ ion in SBF. Both the formed Ta-OH groups combined with Ca2+ ion to form a kind of calcium tantalate, and then with phosphate ion, followed by combination with large amount of Ca2+ ions and phosphate ions to build up apatite layer. The formation rate of Ta-OH groups on the treated tantalum metal predominates the following process including adsorption of Ca2+ ion and phosphate ion on the surface. It is concluded that the acceleration of the apatite nucleation on the tantalum metal in SBF by the NaOH and heat treatments was attributed to the fast formation of Ta-OH group, followed by combination of the Ta-OH groups with Ca2+ and phosphate ions. PMID- 11771703 TI - Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. AB - Application of ultraviolet light (UV-) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble, flexible hydrogel like soft rubber within 60 s. The chitosan hydrogel could completely stop bleeding from a cut mouse tail within 30 s of UV-irradiation and could firmly adhere two pieces of sliced skins of mouse to each other. In order to evaluate its accelerating effect on wound healing, full thickness-skin incisions were made on the back of mice and subsequently an Az-CH-LA aqueous solution was added into the wound and irradiated with UV light for 90 s. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure and healing. Histological examinations also have demonstrated an advanced granulation tissue formation and epithelialization in the chitosan hydrogel treated wounds. The chitosan hydrogel due to its accelerating healing ability is considered to become an excellent dressing for wound occlusion and tissue adhesive in urgent hemostasis situations. PMID- 11771704 TI - Densification route and mechanical properties of Si3N4-bioglass biocomposites. AB - The processing route and the final microstructural and mechanical characteristics of a novel biomaterial composite are described. This new material is composed of 70 wt% Si3N4 ceramic phase and 30 wt% bioglass, the later performing as a liquid sintering aid system and simultaneously providing bioactivity characteristics to the composite. The conditions for fabrication of an almost fully dense material (approximately 98% of relative density) were pursued. Optimised parameters were 1350 degrees C-40 min-30 MPa by hot-pressing technique. The very fast densification rate of the process avoided the crystallisation of the bioglass intergranular phase and therefore its intrinsic properties were maintained. Also, the large amount of glassy phase assured the densification by liquid phase assisted grain rearrangement without Si3N4 phase transformation. The final mechanical properties of the Si3N4 bioglass were as follows: fracture toughness, K(IC) = 4.4 MPa m(1/2); Vickers hardness, Hv = 10.3 GPa; Young's modulus, E = 197 GPa; bending strength, sigma(g) = 383 MPa; Weibull modulus, m = 8.3. These values provide an attractive set of properties among other bioactive materials, namely by upgrading the main drawback of bioceramcs and bioglasses for high-load medical applications, which is the lack of satisfactory fracture toughness. PMID- 11771705 TI - Plasma-induced graft polymerization of acrylic acid onto poly(ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films. AB - Graft polymerization of acrylic acid onto plasma treated poly(ethylene terephthalate) (PET) films was carried out to develop surfaces for protein immobilization and smooth muscle cell seeding. Films with various graft densities were characterized by contact angle measurements, attenuated total reflectance infrared spectroscopy, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The contact angle was observed to decrease from 72.9 degrees for the virgin PET films to between 26 degrees and 33 degrees depending on the graft density. Storage of grafted films led to an increase in the contact angle, suggesting molecular rearrangement at the surface. However, films with the lowest graft levels showed maximum enhancement in the contact angle up on storage. XPS confirmed the presence of the polyacrylic acid grafts at the film surface and AFM showed a marked increase in the wavelength of the surface roughness as the graft density increased. The amount of collagen immobilized at the surface of the grafted films also increased as the graft density increased. The collagen immobilized films provided an excellent substrate for the growth of human smooth muscle cells. PMID- 11771706 TI - Radioisotope carrying polyethylene oxide-polycaprolactone copolymer micelles for targetable bone imaging. AB - The aim of this research is to develop polymeric micelle system as a targetable bone imaging carriers without nonspecific phagocytosis which is made of polyethylene oxide (PEO) and polycaprolactone (PCL). Diamino-PEO, which has two amino groups in its structure, was used to conjugate both PCL and ligand for specific radioisotope. PCL was conjugated to one amino group of diamino-PEO by using diaminohexyl cyclocarbodiimide (DCC), coupling agent. Hydroxyphenylpropionic acid (HPP), diethylenetriamine pentaacetic acid (DTPA) and mercaptoacetyl glycine glycidyl glycine (MAG3), as ligands for specific radioisotopes, were coupled to the rest of amino group of diamino-PEO by the same method as described. Formation of ligand-conjugated block copolymers, critical micelle concentration (CMC) of the copolymers, hydrodynamic radii, and morphology of the micelles were investigated. Besides, 125I-labelling efficiency and biodistribution of the micelles were examined. PEO-PCL block copolymer micelles demonstrated CMC of 25 mg/l and size of 60 nm, which may be adequate for blood vessel and bone imaging. 125I-labelling efficiency was above 90%, and was more stable at human serum for 24 h. 125I-labelled polymeric micelles showed higher blood maintenance and bone uptake when compared to stannous colloid, used as a control. A noticeable decrease in liver or spleen uptake could be achieved by the micelles. Therefore, radioisotope carrying PEO-PCL micelle system was suggested as a useful tool for effective diagnostic bone targeting and imaging. PMID- 11771707 TI - Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity. AB - The most significant complication in external fixation is pin tract infection causally related to the highly adaptive ability of bacteria to colonise the surfaces of "inert" biomaterials or of adjacent damaged tissue cells. The hypothesis that coating a pin with a silver-containing compound will decrease bacterial colonisation and/or pin tract infection has been confirmed in other studies in vitro and in vivo experiments. In this work, biocompatibility of silver-coated orthopaedic external fixation pins was compared with stainless steel controls in an in vitro study. Human peripheral blood lymphocytes were used to assess the possible genotoxic effect of silver, studying the frequency of sister-chromatid exchanges and micronuclei while fibroblasts (NIH 3T3) and osteoblast-like cells were used for cytotoxicity and cytocompatibility studies. These studies have shown that silver is neither genotoxic nor cytotoxic as compared to stainless steel, a material in wide use as a metal implant. At 4 days cells cultured on the silver-coated material evidenced good cell spreading and a higher cell count with respect to the uncoated material. It appears that the addition of silver onto implantable medical devices could be beneficial when specific biological properties, such as antibacterial behaviour, are required. Based on these and the previous bacterial studies it seems like the toxicity towards bacteria was quite a bit greater than that towards the human cells. PMID- 11771708 TI - Photolithographic generation of protein micropatterns for neuron culture applications. AB - Standard positive photoresist techniques were adapted to generate micropatterns of proteins on glass and oxide surfaces. Both lift-off and plasma-etching techniques were used to transfer the photoresist pattern into a layer of covalently immobilised protein. The surface properties of the areas adjacent to the patterns were altered by chemical surface modification. Using a combination of the lift-off and the etching process complementary patterns of two different proteins were generated. The biochemical and biological functionality of the protein patterns were assessed by immunostaining and by investigating the outgrowth of neurites from neurons plated on the patterned substrates. The investigated patterning processes are compatible with microstructuring and thin film processes, and may be used to generate functional surfaces for sensor and neuron culture applications. PMID- 11771709 TI - Effects of polyethylene and alpha-alumina particles on IL-6 expression and secretion in primary cultures of human osteoblastic cells. AB - The effect of two biomaterials, polyethylene and alpha-alumina, on interleukin-6 (IL-6) secretion and expression has been studied in human osteoblasts in primary culture. Human osteoblastic cells were derived from fresh trabecular bone explants removed during total knee arthroplasty. On reaching confluence, cells were subcultured in 6 well plates; the resulting subcultures were incubated until confluence and polyethylene or alpha-alumina particles were added to some while the rest were left as controls. The IL-6 mRNA levels were assessed by reverse transcription (RT) followed by polymerase chain reaction (PCR). IL-6 secretion was measured in the conditioned medium. The IL-6 expression was higher in the presence of both biomaterials. Maximum expression occurred in response to a dose of 50 mg particles well with both biomaterials and was greater after polyethylene particle addition than after alpha-alumina particle addition at this dose. The maximum IL-6 secretion elicited by alpha-alumina was produced at 10 mg particles well while maximum response with polyethylene required 50 mg well. At a dose of 10 mg/well, alpha-alumina particles induced more secretion than 10 mg of polyethylene particles. Nevertheless, at a dose of 50 mg/well maximum secretion was produced with polyethylene particles. In conclusion and in our experimental conditions, polyethylene as well as alpha-alumina increased both the expression and the secretion of IL-6 in human osteoblastic cells in primary culture and stimulation from polyethylene appears stronger than that from alpha-alumina at the same dose. PMID- 11771710 TI - An improvement in sintering property of beta-tricalcium phosphate by addition of calcium pyrophosphate. AB - The sintering behavior of calcium pyrophosphate (CPP, Ca2P2O7)-doped beta tricalcium phosphate [TCP, Ca3(PO4)2], prepared by solid state reaction, was investigated in-situ, using dilatometry. Pure beta-TCP undergoes phase transition to alpha-TCP at about 1200 degrees C; hence pure beta-TCP ceramics should be sintered bclow 1200 degrees C. Pure beta-TCP sintered body can achieve a relative density of only 86% when sintered at 1150 degrees C. However, the addition of CPP in the range of 0.5-3 wt% delays phasc transition of beta-TCP and enables sintering of beta-TCP at 1200 degrees C without a phase transformation to alpha TCP. Due to this effect of CPP added to TCP, CPP-doped beta-TCP ceramics with relative density over 95% could be obtained when sintered at 1200 degrees C for 2 h. PMID- 11771711 TI - Development of butyl elastomer/methacrylate monomer systems as denture soft lining materials. AB - Previous studies have shown elastomer/methacrylate monomer formulations to have good strength; however, water uptake was high and they also suffered from oxidation. This study has looked at the use of three different butyl elastomers, well known for their oxidation resistance, butyl (PB), chlorobutyl (PCB) and bromobutyl (PBB). The tensile and water uptake properties of the three elastomers gelled with ethyl hexyl methacrylate containing 1% ethylene glycol dimethacrylate and 1% lauryl peroxide (5+ formulation from previous studies) were studied. Water uptake of the pure elastomers was also measured. Tensile strengths were low (PCB5+ = 3.09+/-0.12 MPa and PBB5+ = 3.90+/-0.36 MPa); however, elongation to break values were high (PCB5+ = 797+/-17% and PBB5+ = 599+/-13%). Water uptake was high and protracted with none of the formulations reaching equilibrium. The PCB5+ had the highest uptake (approximately 6% at 203 days) with that for PBB5+ and PB5+ at a similar level (approxiamtely 4% at 203 days). None of the materials showed any sign of oxidation. The PBB proved to be the most suitable of the three elastomers for further development in soft lining formulations. PMID- 11771712 TI - The ultrastructure of anorganic bovine bone and selected synthetic hyroxyapatites used as bone graft substitute materials. AB - The objective of this study was to investigate the morphology and organization of apatite crystallites in mature mammalian bone. Anorganic bovine bone was studied in this investigation to allow for the examination of the mineral crystallites after removal of the organic phase. Field-emission low-voltage scanning electron microscopy (FE-LVSEM) was employed to obtain images at nanometer resolution without the application of a conductive coating. Transmission electron microscopy (TEM) of the samples was also performed to confirm the identification of features observed in the SEM and to allow for comparison with earlier studies of bone mineral architecture. For comparison, in order to demonstrate how the interaction of collagen and apatite results in the architecture and crystal structure of bone mineral, two synthetic hydroxyapatite materials were also analyzed: OsteoGen and OsteoGraf/LD300. FE-LVSEM revealed distinctive features of bone mineral: a fibrillar organization of crystallites, a periodic spacing of crystallites along the fibrils consistent with the banding pattern of collagen, inter-fibrillar bridging crystallites, and a plate-like habit of the crystallites. These findings supported the hypothesis, derived from the earlier TEM data of others, that the mineralization of collagen comprising osteoid proceeds by the formation of apatite crystallites within the fibers at selected periodic sites along their length. Moreover, the very presence in this anorganic material of distinct fibers comprised of the crystallites is demonstration of inter-crystallite bonding. The crystallites of the synthetic hydroxyapatite materials did not display any of these ultrastructural features. PMID- 11771713 TI - Surface passivation of a microfluidic device to glial cell adhesion: a comparison of hydrophobic and hydrophilic SAM coatings. AB - Cell adhesion in a microfluidic structure can lead to catastrophic flow problems due to the comparable size of the cell with the microfabricated device. Such issues are important in the growing research area involving the merging of biological materials and MEMS devices. We have examined the surface compatibility of uncoated and coated microfabricated glass and semiconductor surfaces under static solution (cell culture) and flow experiments (microfluidic device) using glial (astrocyte and glioblastoma) cells. Bare semiconductor and glass surfaces were most attractive to cell adhesion, promoting biofouling under both static and flow conditions. Passivation of the surfaces was performed with silane coupling agents octadecyltrimethoxysilane (OTMS) or N-(triethoxysilylpropyl)-O polyethylene oxide urethane (TESP) on SiO2 surfaces via self-assembled monolayer (SAM) deposition. The hydrophilic TESP coating was effective at inhibiting biofouling of the microfluidic structure, allowing greater than several minutes of fluid flow. The hydrophobic OTMS coating, on the other hand, promoted cell adhesion leading to restricted flow within a few minutes. Interestingly, under cell culture conditions the TESP surface exhibited biocompatible properties for glial cell adhesion and proliferation, in contrast to the OTMS surface which resisted cell growth. These studies suggest that cell adhesion is dependent upon the time domain of the cell-surface interaction. PMID- 11771714 TI - Functionalization of synthetic polymers for potential use as biomaterials: selective growth of hydroxyapatite on sulphonated polysulphone. AB - A novel composite made of biocompatible synthetic polymer (Sulphonated Polysulphone, SPSPH) which may be easily fabricated in various shapes and synthetic hydroxyapatite (HAP) was prepared. The preparation was done by the spontaneous precipitation of HAP in aqueous suspensions of the polymer particles. The time the precipitation process was allowed to proceed was used to regulate the inorganic content of the composite. The preparation thus obtained, in addition to its effectiveness in inducing HAP formation, could be easily fabricated in various shapes, including films. The SPSPH-HAP composite films, surface area totaling ca. 30 cm2 induced the exclusive formation of HAP with rates proportional to the solution supersaturation. No induction times preceded the formation of HAP. Kinetics analysis with respect to HAP yielded an apparent order of precipitation of 6.0+/-0.4, suggesting polynuclear growth with the formation of nuclei above nuclei. The surface energy calculated from the rates of crystal growth on the polymeric substrate gave for HAP the value of 185 mJ m(-2) of order of magnitude typical for crystalline solids. PMID- 11771715 TI - Bioactivity of plasma sprayed dicalcium silicate coatings. AB - Dicalcium silicate coatings on titanium alloys substrates were prepared by plasma spraying and immersed in simulated body fluids for a period of time to investigate the nucleation and growth of apatite on the surface of the coatings. Surface structural changes of the specimens were analyzed by XRD and IR technologies. SEM and EDS were used to observe surface morphologies and determine the composition of dicalcium silicate coatings before and after immersion in simulated body fluid. The plasma sprayed dicalcium silicate coating was bonding tightly to the substrate. The coating was mainly composed of beta-Ca2SiO4 and glassy phase. A dense carbonate-containing hydroxyapatite (CHA) layer was formed on the surface of the plasma sprayed dicalcium silicate coating soaked in SBF solution for 2 days. In addition, a silica-rich layer was also observed between CHA layer and coatings. With an increase in the immersion time, the CHA layer gradually became thicker. The results obtained indicated that the plasma sprayed dicalcium silicate coating possesses excellent bioactivity. PMID- 11771716 TI - Connectionist inference models. AB - The performance of symbolic inference tasks has long been a challenge to connectionists. In this paper, we present an extended survey of this area. Existing connectionist inference systems are reviewed, with particular reference to how they perform variable binding and rule-based reasoning and whether they involve distributed or localist representations. The benefits and disadvantages of different representations and systems are outlined, and conclusions drawn regarding the capabilities of connectionist inference systems when compared with symbolic inference systems or when used for cognitive modelling. PMID- 11771717 TI - Analysis of the frequency response of the saccadic circuit: numerical simulations. AB - Fundamental mechanisms of a brain circuit's operation can be revealed by quantitative analysis of the system's dynamic behavior. This approach is particularly useful for investigation of motor circuits, which generate machine like outputs and where systems control techniques can be applied to reveal the circuit behavior outside the dynamic range of volitional activation. As an extension of our previous study of the step response of the saccadic motor system, this paper presents analytical and numerical considerations for the frequency response of the saccadic circuit-the system response to a steady-state sinusoidal input. Consideration of these responses provides mechanistic explanation for several aspects of the biological circuit and formalizes constraints for viable models of the saccadic circuit. Most importantly, these studies provide quantitative predictions for comparison with experimental data in vivo and make explicit hypotheses about biological mechanisms for experimental verification. PMID- 11771718 TI - Unified stabilization approach to principal and minor components extraction algorithms. AB - Principal component and minor component extractions provide powerful techniques in many information processing fields. There have been proposed a number of algorithms for principal and minor component (or subspace) extraction, which have different dynamical behaviors. In this paper, we give rigorous stability analysis of these algorithms, obtaining a unified insight view on the dynamical behaviors of various algorithms. PMID- 11771719 TI - Improvement of generalization ability for identifying dynamical systems by using universal learning networks. AB - This paper studies how the generalization ability of models of dynamical systems can be improved by taking advantage of the second order derivatives of the outputs with respect to the external inputs. The proposed method can be regarded as a direct implementation of the well-known regularization technique using the higher order derivatives of the Universal Learning Networks (ULNs). ULNs consist of a number of interconnected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. A generalized learning algorithm has been derived for the ULNs, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. First, the method for computing the second order derivatives of ULNs is discussed. Then, a new method for implementing the regularization term is presented. Finally, simulation studies on identification of a nonlinear dynamical system with noises are carried out to demonstrate the effectiveness of the proposed method. Simulation results show that the proposed method can improve the generalization ability of neural networks significantly, especially in terms that (1) the robust network can be obtained even when the branches of trained ULNs are destructed, and (2) the obtained performance does not depend on the initial parameter values. PMID- 11771720 TI - Self-organization in the one-dimensional SOM with a decreasing neighborhood. AB - A proof of self-organization for a general, standard, one-dimensional SOM and a monotonically decreasing neighborhood function such that W < or = N, is given, where N is the total number of neurons and W the width of the neighborhood function. It is the generalization of already existing proofs for two specific cases with W > or = N/2. Lebesgue continuity of the distribution of the input is not a requirement. The order p of the SOM, where p = [N/W] + 1, if N mod W not = 0 or else p = NIW, is fundamental to the proof. A total of 2p basic intervals of non-zero probability on the support of the input are sufficient for self organization. These basic intervals are separated by minimum distances which depend on parameters of the SOM (e.g. gain, neighborhood function). The result gives a relationship which in a practical situation can be used to determine, for a given number of neurons and neighborhood function, the minimum number of discrete data points which can guarantee self-organization. PMID- 11771721 TI - Upper bound of the expected training error of neural network regression for a Gaussian noise sequence. AB - In neural network regression problems, often referred to as additive noise models, NIC (Network Information Criterion) has been proposed as a general model selection criterion to determine the optimal network size with high generalization performance. Although NIC has been derived using asymptotic expansion, it has been pointed out that this technique cannot be applied under the assumption that a target function is in a family of assumed networks and the family is not minimal for representing the target true function, i.e. the overrealizable case, in which NIC reduces to the well-known AIC (Akaike Information Criterion) and others depending on a loss function. Because NIC is the unbiased estimator of generalization error based on training error, it is required to derive the expectations of errors for neural networks for such cases. This paper gives upper bounds of the expectations of training errors with respect to the distribution of training data, which we call the expected training error, for some types of networks under the squared error loss. In the overrealizable case, because the errors are determined by fitting properties of networks to noise components, including in data, the target set of data is taken to be a Gaussian noise sequence. For radial basis function networks and 3-layered neural networks with bell shaped activation function in the hidden layer, the expected training error is bounded above by sigma2* - 2nsigma2*logT/T, where sigma2* is the variance of noise, n is the number of basis functions or the number of hidden units and T is the number of data. Furthermore, for 3-layered neural networks with sigmoidal activation function in the hidden layer, we obtained the upper bound of sigma2* - O(log T/T) when n > 2. If the number of data is large enough, these bounds of the expected training error are smaller than sigma2* - N(n)sigma2*/T as evaluated in NIC, where N(n) is the number of all network parameters. PMID- 11771722 TI - The POP learning algorithms: reducing work in identifying fuzzy rules. AB - A novel fuzzy neural network, the Pseudo Outer-Product based Fuzzy Neural Network (POPFNN), and its two fuzzy-rule-identification algorithms are proposed in this paper. They are the Pseudo Outer-Product (POP) learning and the Lazy Pseudo Outer Product (LazyPOP) leaning algorithms. These two learning algorithms are used in POPFNN to identify relevant fuzzy rules. In contrast with other rule-learning algorithms, the proposed algorithms have many advantages, such as being fast, reliable, efficient, and easy to understand. POP learning is a simple one-pass learning algorithm. It essentially performs rule-selection. Hence, it suffers from the shortcoming of having to consider all the possible rules. The second algorithm, the LazyPOP learning algorithm, truly identifies the fuzzy rules which are relevant and does not use a rule-selection method whereby irrelevant fuzzy rules are eliminated from an initial rule set. In addition, it is able to adjust the structure of the fuzzy neural network. The proposed LazyPOP learning algorithm is able to delete invalid feature inputs according to the fuzzy rules that have been identified. Extensive experimental results and discussions are presented for a detailed analysis of the proposed algorithms. PMID- 11771723 TI - Oriented principal component analysis for large margin classifiers. AB - Large margin classifiers (such as MLPs) are designed to assign training samples with high confidence (or margin) to one of the classes. Recent theoretical results of these systems show why the use of regularisation terms and feature extractor techniques can enhance their generalisation properties. Since the optimal subset of features selected depends on the classification problem, but also on the particular classifier with which they are used, global learning algorithms for large margin classifiers that use feature extractor techniques are desired. A direct approach is to optimise a cost function based on the margin error, which also incorporates regularisation terms for controlling capacity. These terms must penalise a classifier with the largest margin for the problem at hand. Our work shows that the inclusion of a PCA term can be employed for this purpose. Since PCA only achieves an optimal discriminatory projection for some particular distribution of data, the margin of the classifier can then be effectively controlled. We also propose a simple constrained search for the global algorithm in which the feature extractor and the classifier are trained separately. This allows a degree of flexibility for including heuristics that can enhance the search and the performance of the computed solution. Experimental results demonstrate the potential of the proposed method. PMID- 11771724 TI - A remark on 'On stability of nonlinear continuous-time neural networks with delays'. PMID- 11771725 TI - On using the Poincare polynomial for calculating the VC dimension of neural networks. PMID- 11771726 TI - Chimeras of the integrin beta subunit mid-region reveal regions required for heterodimer formation and for activation. AB - A central region of the beta2 integrin subunit, RN (residues D300 to C459), was replaced by the equivalent sequences from beta1 and beta7 to give the chimeras beta2RN1 and beta2RN7. Whilst the former construct failed to form heterodimer at the cell surface with alphaL, the later of these could be expressed together with the alphaL subunit to form a variant LFA-1. Based on recent modelling work, the RN region consists of two parts, one is the C-terminal end of the putative A domain (RB, residues D300 to A359), and the other the mid-region (BN, residues Y360 to C459). Chimeras exchanging the two component regions were made. Of the four resultant chimeras, only the beta2RB1 chimera failed to support LFA-1 expression. Thus the beta1 specific residues of this region affect the interaction with the alphaL subunit. Whereas the alphaL/beta2RB7 LFA-1 variant is wildtype like with respect to ICAM-1 adhesion, the alphaLbeta2BN1 and alphaLbeta2BN7, as well as the alphaLbeta2RN7, variants are more adhesive than the wildtype. These results suggest that an authentic beta2 mid-region is, in part, required for maintaining the LFA-1 in a resting state. PMID- 11771727 TI - Contortrostatin, a homodimeric disintegrin, actively disrupts focal adhesion and cytoskeletal structure and inhibits cell motility through a novel mechanism. AB - Integrins play a major role in the regulation of cell motility. They physically link the extracellular environment to the cytoskeleton and participate in large protein complexes known as focal adhesions. In this report, it is demonstrated that treatment of tumor cells with the homodimeric disintegrin contortrostatin induces integrin-mediated tyrosine phosphorylation events and causes severe disruptions in the actin cytoskeleton and disassembly of focal adhesion structures without affecting cellular adhesion to a reconstituted basement membrane. Included in this disruption is the tyrosine phosphorylation and altered subcellular localization of FAK. Through use of transfected 293 cells with specific integrin expression profiles and anti-alphavbeta3 mAbs, we demonstrate that these events are mediated exclusively by the alphavbeta3 integrin and are likely the result of contortrostatin-mediated crosslinking of this receptor at the cell surface, since monovalent disintegrins, flavoridin or echistatin do not induce such effects. Further, it is shown that contortrostatin potently inhibits motility in cells expressing the alphavbeta33 integrin. The results of this study describe a novel integrin-mediated mechanism by which cell motility can be inhibited and suggest an alternative approach to therapeutic intervention for cancer invasion and metastasis. PMID- 11771728 TI - Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta. AB - Transforming growth factor beta1 (TGFbeta) inhibits cellular proliferation, promotes differentiation, and stimulates the expression and secretion of the extracellular matrix adhesion molecules fibronectin and laminin and the colon associated intercellular adhesion molecule carcinoembryonic antigen. This is collectively called the TGFbeta-mediated adhesion response and occurs in the human colon cancer cell line Moser while the cell line KM12SM is relatively unresponsive to TGFbeta. We have previously shown that TGFbeta rapidly stimulates protein kinase C (PKC) phosphotransferase activity in the Moser cells and that the induction of the adhesion response (but not antiproliferation) by TGFbeta is dependent on PKC. Because resistance to growth factors may be due to translational suppression and the translation initiation factor eIF-4E may alleviate translational suppression, we determined the effect of eIF-4E expression on the responses of Moser and KM12SM cells to TGFbeta. Ectopic expression of eIF-4E in the TGFbeta-responsive Moser cells enhanced the activation of PKC by TGFbeta and the induction of the adhesion response, especially the secretion of adhesion molecules, but not the antiproliferative response. Ectopic expression of eIF-4E in the TGFbeta-resistant KM12SM cells increased TGFbeta stimulation of PKC and the TGFbeta-mediated adhesion response (but not antiproliferation). The secretion of adhesion molecules was significantly increased by TGFbeta. These results showed in these cells that eIF 4E promotes TGFbeta-regulated adhesion but not antiproliferation in a PKC dependent manner. PMID- 11771729 TI - Treatment of chronic viral hepatitis. AB - Significant advances have been made in the treatment of both hepatitis B and C. Cure for the majority is becoming reality. Combination regimens are now established therapy in hepatitis C and the near future will see the adoption of a similar approach to hepatitis B. Interferon alpha therapy remains important, with the development of more efficacious pegylated forms. In this article we review current therapy and discuss future strategies of the therapy for chronic viral hepatitis. PMID- 11771730 TI - Stereochemistry as a major determinant of the anti-HIV activity of chiral naphthyl thiourea compounds. AB - Eleven chiral naphthyl thiourea (CNT) compounds were synthesized as non nucleoside inhibitors (NNI) of the reverse transcriptase (RT) enzyme of HIV-1. Molecular modelling studies indicated that, because of the asymmetric geometry of the NNI binding pocket, the 'R' stereoisomers would fit the NNI binding pocket of the HIV-1 RT much better than the corresponding 'S' stereoisomers, as reflected by their 10(4)-fold lower Ki values. The 'R' stereoisomers of all 11 compounds inhibited the recombinant RT in vitro with lower IC50 values than their enantiomers. Of seven CNT compounds whose 'R' stereoisomers exhibited nanomolar IC50 values against recombinant RT, five were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMC). All five 'R' stereoisomers were active anti-HIV agents and inhibited the replication of the HIV-1 strains HTLV-IIIB (NNI-sensitive), A17 (NNI-resistant, Y181C mutant RT) and A17Var (NNI-resistant, Y181C plus K103N mutant RT), as well as primary HIV-1 isolates from AIDS patients in human PBMC at nanomolar concentrations, whereas their enantiomers were inactive. The lead compounds, 1R and 5R, were 3 log more potent than the standard NNI drug nevirapine against the NNI-resistant HIV-1 strains. Our data establish the stereochemistry as a major determinant of the potency of this new class of NNI. PMID- 11771731 TI - Influence of a Calpha-substitution on the S-pivaloyl-2-thioethyl chain on the anti-HIV activity and stability of the resulting zidovudine mononucleoside phosphotriester. AB - We report the synthesis, in vitro anti-HIV-1 activity and stability study of a mononucleoside phosphotriester derivative of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a new biolabile phosphate-protection, namely S-pivaloyl-2 thioisopropyl (tBuSATP). This transient protection was characterized by the presence of a methyl substituent at the Calpha-position of the previously described S-pivaloyl-2-thioethyl (tBuSATE) group. Results demonstrated that the new phosphotriester entity was able to deliver selectively the corresponding 5' mononucleotide within the infected cells. The introduction of a methyl group at the Calpha-position of the tBuSATE chain decreased the rate of this delivery. PMID- 11771732 TI - Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2. AB - We have examined the susceptibility to acyclovir and frequency of acyclovir resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions. PMID- 11771733 TI - Inhibition of measles virus replication by 5'-nor carbocyclic adenosine analogues. AB - Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world, sometimes as the result of severe, chronic, lethal disease. In an effort to develop therapies to supplement immunization strategies, a number of 5'-nor carbocyclic adenosine analogues were evaluated for anti-MV activity in CV-1 monkey kidney cells. Of those compounds tested, those either unsubstituted at C4 or possessing a hydroxyl, azido or amino substituent at that position were the most active, with particularly significant inhibition of MV, strain Chicago-1. The EC50 values against this strain ranged from <0.1 to 1 mg/ml, as determined by cytopathic effect reduction assay, and confirmed by neutral red uptake. By virus yield reduction assay (+)-(1S,25,3R,4S)-4-(6'-amino-9'H-purin-9'-yl)cyclopentane-1,2,3 triol (2) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)-2,3-dihydoxycyclopent-4-ene (3) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)cyclopentane-2,3 dihydoxycyclopentane (5) and (-)-(1R,2R,3R,4S)-4-amino-1-(6'-amino-9'H-purin-9' yl)cyclopentane-2,3-diol (8) were the most potent compounds tested, all with EC90 values of < or =0.4 mg/ml. Compounds 3 and 5 were also tested against other MV strains, and similarly inhibited those strains except for four designated as Bil, Edmonston, SA and X-1108. Compound 8 did not potently inhibit these other MV strains. In addition, 3, 5 and 8 demonstrated synergistic (additive) inhibition of MV replication in combination with ribavirin at several concentrations. Compounds 3, 5 and 8 were also potent MV inhibitors even when added to infected cells 24 h after virus exposure. None of these three compounds was virucidal at concentrations that inhibited viral replication as determined by virus yield reduction assay. Most compounds tested were also not toxic at concentrations >100 mg/ml in actively growing and stationary-phase cells. Results suggest that these compounds may be clinically useful anti-MV virus agents. PMID- 11771734 TI - Intracellular phosphorylation of carbocyclic 3-deazaadenosine, an anti-Ebola virus agent. AB - Carbocyclic 3-deazaadenosine (C-c3Ado) is a potent inhibitor of Ebola virus in mice by infrequent dosing, even though its half life in plasma is only 23-28 min. This prompted studies to determine whether C-c3Ado undergoes intracellular metabolism to derivatives that may promote in vivo activity. In cells, radiolabelled compound readily underwent metabolism to monophosphate, diphosphate and triphosphate (C-c3ATP) forms, with C-c3ATP being the major metabolite detected. A non-polar metabolite was also detected both inside and outside treated cells. The retention time of C-c3ATP was similar but not identical to ATP on a strong anion exchange high performance liquid chromatography (HPLC) column or on a DEAE-Sephadex open column. C-c3ATP and ATP were susceptible to degradation to their respective nucleosides by bovine alkaline phosphatase. Intracellular formation of C-c3ATP reached a plateau by about 4 h after treatment of monkey (Vero 76) and mouse (Balb/3T3 clone A31) cells with 10 or 100 microM extracellular compound. Phosphorylation was linearly dose responsive at 1, 3 and 10 microM. However, the extent of phosphorylation decreased with increasingly higher concentrations (30, 100 and 300 microM). When compound was removed from the medium, the nucleoside cleared the cells within 1 min, whereas C-c3ATP had a half life of decay of 2-3 h in five cell lines. Phosphorylation of C-c3Ado to C c3ATP was not inhibited by cotreatment of cells (at a 20:1 ratio) with adenosine, guanosine, inosine, xanthosine, cytidine or uridine. There was no evidence of incorporation of C-c3Ado (10 microM) into macromolecules of cells over 72 h, whereas adenosine was readily incorporated. C-c3ATP may represent a form of C c3Ado that might contribute to extending its intracellular half life or otherwise exhibit antiviral activity and/or toxicity. PMID- 11771735 TI - Decreased alpha-endosulfine, an endogenous regulator of ATP-sensitive potassium channels, in brains from adult Down syndrome patients. AB - Alpha-endosulfine has the ability to block ATP-sensitive potassium (K(ATP)) channels and stimulate insulin release in beta cells like sulfonylurea. Alpha endosulfine is expressed in a wide range of tissue, including brain and endocrine tissues. Although K(ATP) channels are also present in brain and its regulators have been reported to be involved in the release of neurotransmitters such as acetylcholine that plays an important role in cognitive function, the neurobiological role of alpha-endosulfine has not been studied yet. We examined the expression levels of alpha-endosulfine protein in frontal cortex and cerebellum from patients with Down syndrome (DS) showing Alzheimer's disease (AD) pathology using Western blotting. In frontal cortex, alpha-endosulfine was detected in all of 10 controls, but only 1 (from female) out of 8 DS with weak density. In cerebellum, alpha-endosulfine was also detected in all of 9 controls, but only 1 (from male) out of 6 DS with weak density. The considerably decreased alpha-endosulfine could result in the continuous opening of K(ATP) channels and the subsequent decrease of neurotransmitters release associated with cognition. This study is of significance providing evidence for a biological role of alpha endosulfine in brain and alpha-endosulfine protein could be a pharmacological target for therapeutic intervention. PMID- 11771737 TI - Developmental instability of the cerebellum and its relevance to Down syndrome. AB - It has been recognized for many years that cerebellar abnormalities are frequently observed in association with Down syndrome (DS). An important question to be asked about these and other findings in DS is whether their occurrence (i) is attributable to specific loci on the triplicated chromosome or chromosomal segment or (ii) derives from exaggerated responses secondary to the genetic imbalance resulting from trisomy (Ts). Recently, similar cerebellar alterations were observed in subjects with DS and in Ts65Dn mice (Baxter et al., 2000), mice segmentally trisomic for a portion of chromosome 16, which is homologous for loci on the long arm of human chromosome 21. It was concluded by these authors that the occurrence of similar cerebellar changes in DS and in the DS mouse model resulted from triplication of these homologous loci in the two trisomic organisms, i.e. cerebellar development is affected similarly by homologous loci in each species. They wrote that their study of Ts65Dn mice "correctly predicts an analagous pathology in humans". . . and that. . . "The candidate region of genes on chromosome 21 affecting cerebellar development in DS is therefore delimited to the subset of genes whose orthologs are at dosage imbalance in Ts65Dn mice, providing the first localization of genes affecting a neuroanatomical phenotype in DS." Findings described in this review suggest otherwise--that cerebellar findings in DS and in the Ts65Dn mouse are a result of exaggerated vulnerability in general of the cerebellum to disturbing events and that liability to expression of response(s) is exacerbated by trisomy. This conclusion is based on the following: (i) the cerebellum has an extended postnatal development; (ii) numerous genetic, environmental, epigenetic and metabolic conditions express cerebellar changes similar to those observed in Down syndrome; (iii) most if not all chromosomal imbalance syndromes express similar cerebellar abnormalities; (iv) the cerebellum is particularly sensitive to diverse toxic agents which may act prenatally, postnatally and/or in the mature organism; and (v) cerebellar abnormalities similar to those found in Ts65Dn mice have been described in Ts19 mice which have no segments homologous to any segment of human chromosome 21. An unavoidable conclusion from the review is that triplication of specific loci on 21q is an unlikely explanation for the cerebellar findings in DS. A simple positive control, in which the effect of triplication of loci other than those in question on a specific phenotype, should be used in experiments comparing human and experimental trisomies. As pointed out many years ago by Lorke and his coworkers (Lorke et al., 1989; Lorke, 1994; Lorke and Albrecht, 1994) similar phenotypic findings in the presence of different trisomies in the same species would suggest that the trisomic state itself rather than the gene content of a particular trisomy is responsible for the genesis of traits at issue. PMID- 11771736 TI - Decreased protein levels of complex I 30-kDa subunit in fetal Down syndrome brains. AB - Defects of mitochondrial electron transport enzymes have been implicated in the pathogenesis of several neurodegenerative diseases. In previous work, we reported decreased protein levels of mitochondrial electron transport enzyme subunits in adult brain with Down syndrome (DS). However it is not clear whether cellular damage due to mitochondrial defects in brain of DS fetus begins in utero. Here we investigated the protein levels of mitochondrial electron transport enzymes in fetal DS brain using the proteomic technologies. Two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) and specific software for quantification were used. The protein levels of complex I 30-kDa subunit were significantly decreased in cerebral cortex of fetal DS brain. We conclude that decreased mitochondrial electron transport enzyme subunits in fetal DS brains could contribute to the impaired energy and free radical metabolism affecting brain development in DS fetus. Furthermore, the defects of mitochondrial electron enzymes shown in adult DS brains could begin in utero and continue during the life span of the individual with DS. PMID- 11771738 TI - Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome. AB - The ubiquitin-proteasome proteolytic pathway is involved in an important non lysosomal proteolytic pathway that is responsible for the highly selective turnover of cellular proteins both under basal metabolic conditions as well as stress. Protein degradation by this pathway is attributed to the 20S proteasome that forms the catalytic core of the complex. Recently there has been increasing interest in the proteasome because of its possible role in neuron degeneration and death. Fetal Down syndrome (DS) neurons were demonstrated to degenerate and undergo apoptosis in vitro. We therefore investigated the expression of different proteins involved in this degradative pathway, including subunits of the 20S proteasome, ubiquitinating and deubiquitinating enzymes, and regulatory subunits of the 26S proteasome in control and DS fetal brains by two-dimensional electrophoresis (2-DE). After 2-DE, approximately 389 protein spots were successfully identified by matrix-associated laser desorption ionization mass spectroscopy (MALDI-MS) and this was followed by quantification of twenty three proteins of the pathway. The results indicate that all but two proteins exhibited no apparent alterations in their pattern of expression. Proteasome zeta chain, an alpha subunit of the 20S proteasome (P < 0.05) and ubiquitin carboxy-terminal hydrolase T (Isopeptidase T), a deubiquitinating enzyme (P < 0.001) were significantly increased in fetal DS compared to controls. Whilst the expression of proteasome iota (n = 9, r = -0.9489, P = 0.0004) and proteasome epsilon (n = 9, r = -0.7227, P = 0.0311) chains was decreased with age in fetal DS brain, no significant correlation was obtained in the other proteins with age. The data suggest that such selective upregulation may have relevance to the developmental abnormalities that characterize this disorder. PMID- 11771739 TI - Functional genomics of Down syndrome: a multidisciplinary approach. AB - The availability of the DNA sequence of human chromosome 21 (HSA21) is a landmark contribution that will have an immediate impact on the study of the role of specific genes to Down syndrome (DS). Trisomy 21, full or partial, is a major cause of mental retardation and other phenotypic abnormalities, collectively known as Down syndrome (DS), a disorder affecting 1 in 700 births. The identification of genes on HSA21 and the elucidation of the function of the proteins encoded by these genes have been a major challenge for the human genome project and for research in DS. Over 100 of the estimated 300-500 genes of HSA21 have been identified, but the function of most remains largely unknown. It is believed that the overexpression of an unknown number of HSA21 genes is directly or indirectly responsible for the mental retardation and the other clinical features of DS. For this reason, HSA21 genes that are expressed in tissues affected in DS patients are of special interest. PMID- 11771740 TI - Unaltered expression of Fas (CD95/APO-1), caspase-3, Bcl-2 and annexins in brains of fetal Down syndrome: evidence against increased apoptosis. AB - Apoptosis is the mechanism by which cells are programmed to die under a wide range of physiological and developmental stimuli. Accumulating evidence indicates that enhanced apoptosis (programmed cell death) in Down syndrome (DS) may play a role in mental retardation and precocious neurodegeneration of the Alzheimer type. In this regard, alteration of several apoptosis related proteins have been reported in adult DS brain. Fetal DS neurons exhibited increased reactive oxygen species leading to early apoptosis, however, expression of apoptosis related proteins in fetal DS, has never been considered. To address this issue, we investigated the expression of proteins involved in apoptosis including Fas (CD95, APO-1), caspase-3, Bcl-2 and annexins in the cerebral cortex of control and DS fetal brain by western blot and two dimensional electrophoresis. Here, we report that no detectable changes were obtained in fetal DS brain in the expression of Fas, caspase-3, Bcl-2 and Annexins (I, II, V, and VI) compared to controls. In parallel experiment, we also examined the expression of neuron specific enolase (NSE), a neuronal marker found to be decreased in adult DS brain, to see if there is any neuronal loss and no difference was observed between the two groups. Protein expression did not correlate with age. The unchanged levels of Fas, Bcl-2 and annexins together with unaltered caspase-3 expression, a predominant caspase that executes apoptosis in the developing nervous system, suggest that enhanced apoptosis may not be apparent in fetal DS brain as demonstrated for adult DS brain. PMID- 11771741 TI - Alteration of caspases and other apoptosis regulatory proteins in Down syndrome. AB - Apoptosis has been implicated in the selective neuronal loss of Down syndrome (DS). Apoptosis activates a family of cysteine proteases with specificity for aspartic acid residues referred to as caspases that play a key role in dismantling a cell committed to die. Caspase activity is regulated by a variety of proteins that possess a domain resembling the prodomains of caspases. Little is known, however, about the changes of caspases and their regulatory proteins in DS. Here, we investigated levels of nine such different proteins by western blot technique in frontal cortex and cerebellum of control and DS subjects. The protein levels of DFF45 (DNA fragmentation factor 45), and FLIP (FADD like interleukin-1beta-converting enzyme inhibitory proteins) were significantly decreased whereas that of RICK (RIP-like interacting CLARP kinase) increased in both regions of DS. In contrast, cytochrome c, Apaf-1 (apoptosis protease activating factor-1), procaspase-9 and ARC (apoptosis repressor with caspase recruitment domain) were unchanged. Procaspase-3 and -8 were significantly decreased in frontal cortex but no significant change was observed in cerebellum. Regression analysis revealed no correlation between postmortem interval and levels of the investigated proteins. However, inconsistent correlation was found between age and levels of proteins as well as amongst the density of individual proteins. These findings demonstrate that dysregulation of apoptotic proteins does exist in DS brain and may underlie the neuropathology of DS. The study further suggests that apoptosis in DS may occur via the death receptor pathway independent of cytochrome c. Hence, therapeutic strategies that target caspase activation may prove useful in combating neuronal loss in this disorder. PMID- 11771742 TI - Expression of apoptosis related proteins: RAIDD, ZIP kinase, Bim/BOD, p21, Bax, Bcl-2 and NF-kappaB in brains of patients with Down syndrome. AB - Down syndrome (DS) is a genetic disease that exhibits significant neuropathological parallels with Alzheimer's disease (AD). One of the features of DS, neuronal loss, has been hypothesized to occur as a result of apoptosis. An increasing number of proteins are implicated in apoptosis and several of them were shown to be altered in AD, however, the knowledge in DS is far from complete. To further substantiate the hypothesis that apoptosis is the underlying mechanism for neuronal loss and contribute towards the current knowledge of apoptosis in DS, we analyzed the expression of apoptosis related proteins in frontal cortex and cerebellum of DS by western blot and ELISA techniques. Quantitative analysis revealed a significant increase in DS frontal (P < 0.0001) and cerebellar (P < 0.05) Bim/BOD (Bcl-2 interacting mediator of cell death/Bcl-2 related ovarian death gene), cerebellar Bcl-2 (P < 0.01) as well as p21 (P < 0.05) levels compared to controls. No significant change was detected in Bax, RAIDD (receptor interacting protein (RIP)-associated ICH-1/CED-3-homologus protein with death domain), ZIP (Zipper interacting protein) kinase and NF-kappaB p65 levels in both regions, although frontal cortex levels of RAIDD, Bcl-2 and p21 levels tended to increase. In addition, a 45 kDa truncated form of NF-kappaB p65 displayed a significant elevation (P < 0.05) in DS cerebellum. No significant correlation had been obtained between postmortem interval and level of the proteins analyzed. With regard to age, it was only NF-kappaB p65 that showed significant correlation (r = -0.8964, P = 0.0155, n = 9) in frontal cortex of controls. These findings provide further evidence that apoptosis indeed accounts for the neuronal loss in DS but Bax and RAIDD do not appear to take part in this process. PMID- 11771743 TI - Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down syndrome and Alzheimer's disease. AB - Oxidative stress is considered to be crucial in the pathogenesis of Alzheimer's disease-like neurodegeneration. An elevation of carbonyl compounds that are biomarkers of and leading to oxidative stress has been demonstrated in Down Syndrome (DS) and Alzheimer's Disease (AD) brains and seems to be the result of a multifactorial process. Carbonyls, which are cytotoxic metabolic intermediates, are detoxified by either oxidation catalyzed by aldehyde dehydrogenase (ALDH), or by reduction to their corresponding alcohols by carbonyl reductase (CBR) and/or alcohol dehydrogenase (ADH). We quantified protein levels of CBR and its agonist/antagonist ADH using 2D gel electrophoresis with subsequent MALDI identification and specific software in several brain regions of DS as well as AD patients and compared them to levels of CBR and ADH in brains of controls. Protein levels of both enzymes were increased in several brain regions because of enzyme induction by elevated carbonyls in DS and AD. Increased CBR in DS (trisomy 21) may be due to a gene dosage effect as the gene encoding CBR has been mapped to chromosome 21. These findings may confirm the proposed increase of reactive carbonyls in the brain thus supporting the involvement of oxidative stress and contribute to the understanding of carbonyl handling in brain of both neurodegenerative disorders. PMID- 11771744 TI - Carbohydrate handling enzymes in fetal Down syndrome brain. AB - Impaired glucose metabolism in adult Down Syndrome (DS) has been well-documented in vivo and information on the underlying biochemical defect i.e. aberrant glucose handling enzymes is already available. Nothing is known on carbohydrate handling, however, in early life of DS patients, when no secondary phenomena as e.g. Alzheimer-like neuropathology occur in the brain yet. We therefore determined a series of key enzymes of carbohydrate metabolism in fetal control and DS brain during the early second trimenon. We used two-dimensional electrophoresis with subsequent MALDI characterization and specific software for quantification of protein spots. We observed comparable levels of phosphoglycerate mutase, phosphoglycerate kinase 1; fructose-biphosphate aldolase A, fructose bisphosphate aldolase C; ribose-phosphate pyrophosphokinase 1; D phosphoglycerate dehydrogenase, 6-phosphogluconolactonase; aflatoxin B1 aldehyde reductase 1, aldose reductase; inosine-5'-monophosphate dehydrogenase 2; galactokinase, in brain of fetal controls and DS. We conclude that our biochemical findings point to the fact that DS patients start early life with unchanged glucose handling, pentose phosphate shunt, glycolysis, sugar aldehyde, guanine nucleotide- and ribonucleoside formation and galactose metabolism. PMID- 11771745 TI - Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer's disease. AB - Cholinergic deficit associated with loss of nicotinic acetylcholine receptors (nAChRs) has been described in Alzheimer's disease (AD) by receptor binding assays, positron emission tomography and immunoblotting. However, little is known about the alteration of these receptors in a related disease, Down syndrome (DS) which might be of importance for therapeutic strategies. The protein levels of neuronal nAChR alpha and beta subunits in human postmortem brain samples (frontal cortex and cerebellum) of control, adult DS, and AD were investigated by making use of western blot analysis. Two major bands at 26 and 45 kDa for alpha3, one at 50 kDa for alpha4 and beta2, and one at 45 kDa for alpha7 were detected by the respective antibodies. Specific alteration in individual subunits was also apparent in DS and AD. In frontal cortex, the 45kDa alpha3 subunit was significantly increased in DS (121%) (P < 0.05) and AD (93%) (P < 0.05), whereas the 26kDa, an isoform/truncated form of alpha3, displayed a reversed pattern. It was significantly decreased in DS (75%) (P < 0.001) and AD (52.6%) (P < 0.05). Alpha4 was comparable in all groups by contrast, alpha7 was significantly decreased in AD (64%) (P < 0.05). In DS, however, although the levels tended to be lower (17.3%) the reduction was not significant. Beta2 was unchanged in AD but showed a significant increase in DS frontal cortex (98.1%) (P < 0.01). In cerebellum, no significant alteration was observed in any of the subunits except beta2. It exhibited a significant increase (161%) (P < 0.01) in DS. Derangement in expression of nAChRs is apparent in DS, as in AD that may have some relevance to DS neuropathology. Furthermore, the increase in beta2 expression indicate that these subunits may have more than a structural role. Hence, therapeutic strategies tailored towards these end might be of some benefit for cognitive enhancement in these disorders. PMID- 11771746 TI - Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down syndrome. AB - Human peroxiredoxin (Prx) play important roles in eliminating hydrogen peroxide generated during cellular mechanisms using electrons from thioredoxin (Trx). Oxidative stress induced by reactive oxygen species (ROS) such as hydrogen peroxide has been implicated in the pathogenesis of several neurodegenerative diseases. We applied the proteomic approach to study protein levels of three subtypes of human Prx in brain regions from patients with Alzheimer's disease (AD) and Down Syndrome (DS). Protein levels of Prx-I and Prx-II were significantly increased in AD and DS. Protein levels of Prx-III, a mitochondrial protein, however, were significantly decreased. We conclude that increased protein levels of Prx-I and Prx-II could provide protection against neuronal cell death induced by hydrogen peroxide. Decreased protein levels of Prx-III could be caused by mitochondrial damage shown in AD and DS. Showing upregulated Prx protein levels provides evidence for the involvement of ROS in the pathogenesis of AD and DS. PMID- 11771747 TI - Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. AB - Subjects with Down syndrome exhibit various types of cognitive impairment. Neuropathological and neurochemical studies revealed similarities between Down syndrome and Alzheimer's disease, cholinergic deficits being the most consistent findings. To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5-31 years) received placebo and a single dose of transdermal nicotine (5 mg patch) over 2h in a single-blind, within-subjects repeated measures design. Auditory event-related potentials (ERPs) and neuropsychological tests, comprising digit symbol performance subtest from WAIS-R and the Frankfurt Attention Inventory (FAIR) were performed. Effects of nicotine administration in Down syndrome individuals were a decrease of ERP-P3 latency in 7 of 8 subjects (electrode position Cz: 386.9+/-24.0 ms vs. 363.1+/ 26.9.2 ms, placebo vs. nicotine, respectively; P = 0.058) and an increase of ERP P3 amplitude in 6 of 8 subjects (electrode position Cz: 17.4+/-5.5 vs. 18.0+/-4.5 microV, placebo vs. nicotine respectively; P = 0.725). Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects. PMID- 11771748 TI - The brain in Down syndrome. AB - Down syndrome (trisomy 21) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. We tried to discuss the role of neurodevelopmental abnormalities in connection with aberrant expression of genes on chromosome 21 including amyloid precursor protein (APP), CuZn superoxide dismutase (SOD1) and glial-derived S100 beta protein for neurodegeneration in DS. In this model, alterations in developmental pathways due to aberrant gene expression can impair cellular homeostasis and predispose to neurodegeneration of certain brain regions and types of nerve cells, involving cholinergic, serotonergic and catecholaminergic transmission, by shifting balance toward a pro apoptotic state. PMID- 11771749 TI - Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease. AB - ARPP-19 (cAMP-regulated phosphoprotein of Mr = 19,000) is a substrate for cAMP dependent protein kinase (PKA). ARPP-19 is found in all brain regions but the function of ARPP-19 is not fully elucidated yet. We detected a downregulated sequence with 100% homology with ARPP-19 in temporal cortex of patients with Down syndrome (DS) as compared to controls, but not in Alzheimer's disease (AD) using differential displaypolymerase chain reaction (DD-PCR). We subsequently determined protein levels of ARPP-19 in temporal cortex and cerebellum by immunoblotting and observed significant reduction of ARPP-19 in DS (temporal cortex) and AD (cerebellum). We also observed decreased activities of PKA in DS (temporal cortex and cerebellum) and AD (temporal cortex). These findings suggest that decreased ARPP-19 along with decreased activities of PKA is involved in pathomechanisms of both neurodegenerative disorders. Furthermore, these findings provide first evidence for an impaired mechanism of cAMP-related signal transduction and phosphorylation in both dementing disorders. PMID- 11771750 TI - Increased protein levels of heterogeneous nuclear ribonucleoprotein A2/B1 in fetal Down syndrome brains. AB - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are predominantly nuclear RNA binding proteins that form complexes with RNA polymerase II transcripts. These proteins play pivotal roles in transcription, pre-mRNA processing in the nucleus, cytoplasmic mRNA translation and its turnover. In addition, hnRNPs have been shown to be essential for embryonic development of Drosophila. Here we studied the protein levels of hnRNPs (A2/B1, H and H') in fetal brain with Down syndrome (DS; n = 5) compared to controls (n = 7). We used two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) and specific software for quantification. hnRNP A2/B1 was significantly increased in fetal DS brain (13.52+/-4.50) compared to controls (9.16+/-1.35), but both hnRNP H and H' were unchanged. Increased hnRNP A2/B1 in fetal DS brain may represent high activity of RNA processing such as RNA trafficking and telomere protection, and/or it could contribute to abnormal development of DS brains. Furthermore, comparable expression of hnRNP H and H' suggest a specific upregulation of hnRNP A2/B. PMID- 11771751 TI - Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease. AB - Stathmin, distributed in neurons with high abundance, acts as an intracellular relay, integrating various transduction pathways triggered by extracellular signals and it is involved in physiological regulation of microtubule destabilization. Stathmin has been also shown to be a critical molecule in pathology of neurodegeneration such as Alzheimer's disease (AD), particularly, in neurofibrillary tangle (NFT) formation. Here we evaluated protein levels of stathmin in adult brain from patients with AD and Down syndrome (DS) showing AD like pathology by applying proteomic technologies with two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) identification and specific software for quantification of proteins. Significantly decreased protein levels of stathmin were observed in frontal (2.12+/-1.17, n = 6) and temporal (3.05+/-2.81, n = 10) cortices of AD compared to controls (frontal cortex: 4.41+/-1.70, n = 8; temporal cortex: 5.26+/-2.26, n = 13). Stathmin was also significantly decreased in frontal (2.47+/-1.11, n = 7) and temporal (2.02+/-1.18, n = 9) cortices of DS. We also investigated stathmin levels in fetal brain. Stathmin was not significantly changed between fetal DS brain and controls. We suggest that the decreased protein level of stathmin in brains is associated with tangle formation and microtubule instability in DS as well as AD, but stathmin is not involved in the abnormal development of fetal DS brain. PMID- 11771752 TI - Molecular neuropathology of transgenic mouse models of Down syndrome. AB - Down syndrome (DS) is a complex, clinically heterogeneous disorder which shows both impairment of neurodevelopement and the neurodegenerative changes of Alzheimer's disease (AD). The phenotype of DS is caused by triplication of chromosome 21 and transgenic mouse models have been developed, and are being created, that carry single genes and chromosomal segments to excess. For example, transgenic mice containing additional copies of the amyloid precursor protein (APP) gene, have been useful in producing the Abeta deposition characteristic of AD and DS, but not the cytoskeletal changes that are the hallmarks of these human disorders. Such models are useful in replicating aspects of pathogenesis and allow for the testing of therapeutic agents to restore impaired function. Segmental trisomic mouse models, which survive to adulthood and possess three copies of multiple genes responsible for the DS phenotype, such as Ts1Cje and Ts65Dn, have been used to explore aspects of neurodevelopment and neurodegeneration. These animal models show some but not all the pathological, biochemical, and transcriptional changes seen in DS. They also have the advantage of allowing for the testing of therapeutic agents to restore impaired function. Analysis of the transcriptome and proteome of fetal and adult DS indicates that there is a complex relationship between gene dosage, gene and protein expression, and that data from animal models will need to be compared and evaluated in the light of data obtained from DS tissue. PMID- 11771753 TI - Down syndrome patients start early prenatal life with normal cholinergic, monoaminergic and serotoninergic innervation. AB - Information on the fetal brain in Down syndrome (DS) is limited. In particular, there is no systematic study available on cholinergic, monoaminergic or serotoninergic innervation in the early second trimester. It was therefore the aim of the study to investigate whether deficits of any of these systems known to occur in adults with DS, was present at this early phase. For this purpose we determined markers for neuronal density (neuron-specific enolase, NSE), for cholinergic innervation (vesicular acetylcholine transporter, VAChT), for monoaminergic innervation (vesicular monoamine transporter 2, VMAT2; tyrosine hydroxylase, TH) and for the serotoninergic system (serotonine transporter, SERT) in brain of control and DS fetuses in the early second trimester using immunoblotting. Values for all neurotransmission systems were measurable at this time point of human development and comparable in control and DS fetuses. We conclude that during the second trimester DS patients do not differ in terms of immunoreactivity for all markers studied. This first study on that subject warrants further investigations for the determination of the time point when neurotransmitter deficits in DS brain are starting, a hallmark most important for pathogenesis and pharmacotherapy. PMID- 11771754 TI - Expression profiles of proteins in fetal brain with Down syndrome. AB - Proteomics is a powerful tool for evaluating differential protein expression comparing hundreds of proteins simultaneously. In the current study we performed "gene hunting" at the protein level and identified and quantified 10 protein spots in control and Down syndrome (DS) fetal brains. Using two-dimensional (2-D) electrophoresis of fetal brain proteins with subsequent MALDI-identification and quantification with specific software, we identified a series of poorly known proteins, in part hypothetical and orphans or poorly documented proteins. Hypothetical protein DKFZp564D177.1-human (fragment), one of these proteins was identified in fetal brain and was significantly decreased in DS (0.61+/-0.44, n = 7) compared to controls (3.43+/-1.83, n = 7). Septin 6, previously shown to be associated with synaptic vesicles, was present in all of 7 controls, but only in 1 out of 6 DS brains. We suggest that decreased protein levels of hypothetical protein DKFZp564D177.1-human (fragment) and lower prevalence of septin 6 could be involved in the maldevelopment of fetal DS brains. The other 8 proteins (WD repeat protein 1, novel protein highly similar to septin 2 homolog, septin 5, septin 2, DJ37E16.5 (novel protein similar to nitrophenylphosphatases from various organism), hypothetical 30.2 kDa protein, neuronal protein NP25, and DC7 protein (vacuolar sorting protein 29)) were comparable between controls and DS but could be identified in fetal and DS cortex, thus proposing them as tentative brain proteins. PMID- 11771755 TI - Expression patterns of chaperone proteins in cerebral cortex of the fetus with Down syndrome: dysregulation of T-complex protein 1. AB - Chaperone proteins reduce stress-induced denaturation and aggregation of intracellular proteins and exert protective actions by interfering with the stress-induced apoptotic pathway in the neuronal cells. Although many studies have focused on the critical role of chaperones in protein folding and their relevance in protein conformational diseases such as Alzheimer's disease (AD) and prion disease, limited information is available on their expression pattern in AD related disease, Down Syndrome (DS). In a previous study, we reported differentially expressed molecular chaperone proteins in the brains of adult DS patients. This report demonstrated the relevance of the aberrant expression patterns to biochemical and neuropathological abnormalities in adult DS brain. To investigate whether this aberrant expression patterns already exist in second trimester DS brain, we performed two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-associated laser desorption ionization mass spectroscopy (MALDI-MS) using fetal DS brain. We unambiguously identified and quantified twelve heat shock proteins (HSPs), three glucose regulated proteins (GRPs) and eight T-complex 1 (TCP-1) subunits. Unlike in adult brain with DS, these studies provide evidence for the normal response of most molecular chaperone proteins at the given time point of DS brain development. However, chaperonin protein TCP-1 alpha and beta subunits showed a significant decrease (P < 0.05) in second trimester brain with DS. Comparable response of chaperone proteins in fetal DS brain suggests that not heat-shock induced proteins but rather chaperonin protein TCP-1 may contribute significantly to neuropathogenesis in the early second trimester DS brain. This study extends observations of distinct expression patterns of molecular chaperones in DS brain and we discuss the relevance of aberrant TCP-1 expression patterns to developmental DS brain at the early stage. PMID- 11771756 TI - Beta-amyloid precursor protein, ETS-2 and collagen alpha 1 (VI) chain precursor, encoded on chromosome 21, are not overexpressed in fetal Down syndrome: further evidence against gene dosage effect. AB - Down syndrome (DS) is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and characterized clinically by somatic anomalies, mental retardation and precocious dementia. The phenotype of DS is thought to result from overexpression of a gene or genes located on the triplicated chromosome or chromosome region. Reports that challenge this notion, however, have been published. To add to this body of evidence, the expression of beta amyloid precursor protein (APP), ETS-2 and collagen alpha1 (VI) chain precursor, encoded on chromosome 21, was investigated in fetal brain by western blot and two dimensional electrophoresis (2-DE). Western blot detected APP and ETS-2 that migrated at approximately 75 and 50kDa, respectively. Subsequent densitometric analysis of APP and ETS-2 immunoreactivity did not produce any significant change between controls and DS. Since the metabolic fate of APP determines the propensity of amyloid beta production, the expression of the secreted forms of APP (sAPP) had been examined. Neither the expression of sAPPalpha nor sAPPbeta showed any detectable changes among the two groups. Collagen alpha1 (VI) chain precursor, a protein resolved as a single spot on 2D gel was identified by matrix associated laser desorption ionization mass spectroscopy. Quantitative analysis of this spot using the 2D Image Master software revealed a significant decrease in fetal DS (P < 0.01) compared to controls. Linear regression analysis did not show any correlation between protein levels and age. The current data suggest that overexpression per se can not fully explain the DS phenotype. PMID- 11771757 TI - Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain. AB - Information on the various factors leading to impairments in the developing brain of fetal Down Syndrome patients is limited to few histological reports. We therefore attempted to describe expression levels of proteins in brain using the proteomic technique of two-dimensional electrophoresis with subsequent mass spectroscopical identification of protein spots and quantification with specific software. Cortical tissue was obtained from autopsy of human fetal abortus. Protein levels of GTP-binding nuclear protein ran, guanine nucleotide-binding protein g(o), alpha subunit 2, guanine nucleotide-binding protein g(i)/g(s)/g(t) beta subunit 1, -beta subunit 2, guanine nucleotide-binding protein beta subunit 5, nucleoside diphosphate kinase A, nucleoside diphosphate kinase B, Rab GDP dissociation inhibitor beta, Rho GDP-dissociation inhibitor 1, biphosphate 3' nucleotidase, small glutamine-rich tetra-tricopeptide repeat-containing protein and histidine triad nucleotide-binding protein were studied. Quantification revealed statistically significant reduced levels of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide binding protein in fetal DS brain as compared to controls. We conclude that in early prenatal life proteins involved in neural differentiation, migration and synaptic transmission are impaired in DS cortex. These results may help to understand the abundant mechanisms leading to abnormalities in the wiring, structure and function of DS brain. PMID- 11771758 TI - Expression of the multidrug resistance P glycoprotein (Pgp) and multidrug resistance associated protein (MRP1) in Down syndrome brains. AB - Transport by ATP-dependent efflux pumps such as P glycoprotein (Pgp) and multidrug resistance associated protein (MRP), encoded by multidrug resistant (MDR) associated genes, is an increasingly recognized mechanism by which cells maintain substrate homeostasis and evade drug therapy. Pgp and MRP are members of the so-called ATP binding cassette (ABC) transporters superfamily, which are associated with many biological processes in both prokaryotes and eukaryotes, as well as clinical problems. The observation of upregulated sequences that are homologous to the Mycobacterium smegmatis phage resistance (mpr) gene and putative ABC transporters subunits in fetal Down syndrome (DS) using the gene hunting technique, subtractive hybridization formed the Rationale for this study. The expression of Pgp and MRP1 is therefore investigated in different brain regions of controls and adult DS patients with western blot technique. No apparent changes were observed between controls and DS in levels of Pgp in all brain regions examined. By contrast, MRP1 detection using the rat monoclonal antibody (MRPr1) produced a significant elevation in DS temporal cortex (P < 0.01) and parietal cortex (P < 0.05). Although MRP1 detected with the mouse monoclonal antibody (MRPm6) tended to increase in most of the regions of DS brain, it failed to reach significance level. Age or postmortem interval did not correlate with protein levels in both controls as well as DS. Taken together, the current data provide evidence for the presence of MDR related pumps in different regions of the human brain. In addition, overexpression of MRP1 in DS brain may have some relevance to the disorder either by deranging substrate homeostasis or limiting drug access. PMID- 11771759 TI - Alteration of gene expression in Down's syndrome (DS) brains: its significance in neurodegeneration. AB - Several groups have reported pro-apoptotic alteration of gene expression in Down's syndrome (DS) brains. Aged DS brains manifest a similar neuropathology to Alzheimer's disease (AD), including the presence of senile plaques (SP) and neurofibrillary tangles (NFT). Although it is controversial if neurodegenerative processes play a pathological role in DS brains, evidence such as cortical neurons from fetal DS brains showing vulnerability to cell death when compared with neurons from control subjects supports this point of view. In this chapter, we review the reports that demonstrate pro-apoptotic alteration of gene expression in DS brains. In addition to the pathogenic genes on chromosome 21, such as amyloid precursor protein (APP) and CuZn-superoxide dismutase (SOD1), other genes which associate with p53, or with processes for protein folding have been frequently found. PMID- 11771760 TI - Deterioration of the transcriptional, splicing and elongation machinery in brain of fetal Down syndrome. AB - Perturbation of brain development i.e. regulation of gene expression, differentiation, growth and migration in Down Syndrome (DS) has been reported to occur early in life pointing to impairment of the complex system of transcription and or translation and indeed, altered expression of transcription factors has been reported in adult DS brain. We therefore decided to compare the transcriptional and translational machinery in cortex of brains of controls and fetuses with Down syndrome in the second trimenon of gestation. We determined a series of transcription/translation factors by 2 D-electrophoresis followed by MALDI--identification and quantification with specific software. The protooncogene C-CRK, CRK-like protein, elongation factor 1-alpha 1, elongation factor 2, elongation factor tu and two out of four spots representing PTB associated splicing factor PSF were significantly downregulated in brain of fetal DS fetuses as compared to controls. The finding of reduced transcription and translation factors may indicate deranged protein synthesis. The underlying cause for individual reduced transcription, splicing and translation factors may be explained by chromosomal imbalance or by posttranslational modifications as e.g. phosphorylation, known to be aberrant in DS. Reduced expression of transcription factors in fetal DS during early life may be responsible or reflecting impaired brain development and deficient wiring of the brain in DS. PMID- 11771761 TI - Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. AB - Information on fetal brain in Down Syndrome (DS) is limited and there are only few histological, mainly anecdotal reports and no systematic study on the wiring of the brain in early prenatal life exists. Histological methods are also hampered by inherent problems of morphometry of neuronal structures. It was therefore the aim of the study to evaluate neuronal loss, synaptic structures and dendritic spines in the fetus with Down Syndrome as compared to controls by biochemical measurements. 2 dimensional electrophoresis with subsequent mass spectroscopical identification of spots and their quantification with specific software was selected. This technique identifies proteins unambiguously and concomitantly on the same gel. Fetal cortex samples were taken at autopsy with low post-mortem time, homogenized and neuron specific enolase (NSE) determined as a marker for neuronal density, the synaptosomal associated proteins alpha SNAP [soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein], beta SNAP, SNAP 25 and the channel associated protein of synapse 110 (chapsyn 110) as markers for synaptosomal structures and drebrin (DRB) as marker for dendritic spines. NSE, chapsyn 110 and beta SNAP were comparable in the control fetus panel and in Down Syndrome fetuses. Drebrin was significantly and remarkably reduced and not even detectable in several Down Syndrome brain samples. Quantification of SNAP 25 revealed significantly reduced values in DS cortex and alpha SNAP was only present in half of the DS individuals. We conclude that at the time point of about 19 weeks of gestation (early second trimester) no neuronal loss can be detected but drebrin, a marker for dendritic spines and synaptosomal associated proteins alpha SNAP and SNAP 25 were significantly reduced indicating impaired synaptogenesis. Early dendritic deterioration maybe leading to the degeneration of the dendritic tree and arborization, which is a hallmark of Down Syndrome from infancy. PMID- 11771762 TI - Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. AB - Exposure of living organisms to reactive oxygen species (ROS), notably oxygen free radicals and hydrogen peroxide is closely linked to the very fact of aerobic life. Oxidants, however, are not always detrimental for cell survival, indeed moderate concentrations of ROS serve as signaling molecules. To maintain this level, cells have evolved an antioxidant defense system. Disruption of this balance leads either to oxidative or reductive stress. Down syndrome (DS) is a genetic disorder associated with oxidative stress. Overexpression of superoxide dismutase-1 (SOD-1) as a result of gene loading is suggested to be responsible for this phenomenon. To examine this view, we investigated the expression of thirteen different proteins involved in the cellular antioxidant defense system in brains of control and DS fetuses by two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization mass spectroscopy (MALDI MS). No detectable change was found in expression of SOD-1, catalase, phospholipid hydroperoxide glutathione peroxidase, glutathione reductase, antioxidant enzyme AOE372, thioredoxin-like protein and selenium binding protein between control and DS fetuses. By contrast, a significant reduction was observed in levels of glutathione synthetase (P < 0.01), glutathione-S-transferase mu2 (P < 0.01), glutathione-S-transferase p (P < 0.05), antioxidant protein 2 (P < 0.05), thioredoxin peroxidase-I (P < 0.05) and thioredoxin peroxidase-II (P < 0.01) in DS compared with controls. The data suggest that oxidative stress in fetal DS does not result from overexpression of SOD-1 protein, rather oxidative stress appears to be the consequence of low levels of reducing agents and enzymes involved in removal of hydrogen peroxide. PMID- 11771763 TI - Glial-neurotrophic mechanisms in Down syndrome. AB - Complex interactions and interconnectivity between neurons are hallmarks of normal neuronal differentiation and development. Neurons also interact with other cell types, notably glia, and rely on substances released by glia for their normal function. A deficit in glial response may disturb this critical neuronal glial-neuronal interaction in Down syndrome (DS), leading to loss of neurons and other defects of development, and contribute to cognitive limitation and early onset of Alzheimer disease. The hypothesis this paper will discuss is that normal neural development involves an activity-dependent release of substances from neurons, and that these substances act upon glia cells which in turn release substances that influence neurons to promote their survival and development. This glial influence affects cortical neurons and also the subcortical cholinergic neurons that project to the cerebral and hippocampal cortices to maintain cortical neuronal excitability and activity. The neuronal activity stimulates glial secretion of sustaining substances, in a reciprocally interactive cycle. Some aspect of this "virtuous cycle" is deficient in Down syndrome. The result is a small but slowly increasing deficit in activity-dependent support by glia cells which produces a gradually increasing abnormality of cortical and subcortical, perhaps especially cholinergic, function. PMID- 11771764 TI - Aberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain. AB - Pathfinding of growing axons to reach their target during brain development is a subtle process needed to build up contacts between neurons. Abnormalities in brain development in Down Syndrome (DS) are described in a couple of morphological reports but the molecular mechanisms underlying abnormal wiring in fetal DS brain are not yet elucidated. We therefore performed a study using the proteomic approach to show differences in protein levels involved in the guidance of axons between control and DS brain in early prenatal life. Proteins obtained from autopsy of human fetal abortus were applied on 2-dimensional gel, identified and quantified. We quantified 5 members of the semaphorin/collapsin family, the dihydropyrimidinase related proteins 1-4 and the collapsin response mediator protein-5 (CRMP-5) in 8 DS and 7 control cortex samples. DRP-1 and CRMP-5 levels were comparable in the control and DS samples. Evaluation of DRP-2, DRP-3 and DRP 4 revealed significantly decreased levels of 2 of the 15 spots assigned to DRP-2 and increased levels of one spot assigned to DRP-3 and increased DRP-4 in DS brain. We conclude that as early as from the 19th week of gestation pathfinding cues of the outgrowing axons are impaired in DS. These findings may help to elucidate mechanisms leading to abnormalities in neural migration of DS brain. PMID- 11771765 TI - ALS--future directions. PMID- 11771766 TI - COX-2 and ALS. PMID- 11771767 TI - The diagnostic pathway in amyotrophic lateral sclerosis. AB - INTRODUCTION: We present the findings of a survey of the diagnostic pathways and treatment of 50 patients with amyotrophic lateral sclerosis (ALS). RESULTS: The mean time between first symptoms and first consultation with a physician was 5.7 months; mean time between first symptoms and first consultation with a neurologist was 9.7 months; mean time from symptom onset to confirmation of diagnosis was 11.6 months. Patients with bulbar onset appeared to be diagnosed earlier than those with limb onset, but the difference was not statistically significant. The first physician seen was an orthopedist in 30%, a general practitioner (GP) in 28%, and a neurologist in 28% of cases. The mean diagnostic intervals were 9.4 months when the neurologist was the first physician seen, and 9.8 months when the neurologist saw a patient referred from a GP. Otherwise, when a neurologist saw patients referred from an orthopedist, the mean diagnostic interval was 14.9 months. Differences between the values of mean diagnostic interval were not statistically significant. EMG and MRI were performed in all patients, cerebrospinal fluid examination and muscle biopsy in most. Treatment was by vitamins in 38% of cases, thyrotropin-releasing hormone in 24%, physical therapy in 22%, and anticholinesterase agent in 12%. CONCLUSION: The number of patients in our study is limited, and a further prospective nation-wide survey is necessary. PMID- 11771768 TI - A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis. AB - INTRODUCTION: The p75 neurotrophin receptor has been recognized as a death signalling molecule under certain circumstances. Its role in motor neuron degeneration in amyotrophic lateral sclerosis (ALS) was analysed in SOD1-G93A transgenic mice and in spinal cords from human amyotrophic lateral sclerosis. METHOD: The precise loss of motor neurons in SOD1-G93A transgenic mice from birth to adulthood was established using the unbiased fractionator/optical dissector neuronal counting technique. RESULTS: This study showed an early trend in the loss of lumbar motor neurons in SOD1-G93A mice, beginning at birth and progressing to a massive 80% reduction by 4 months of age, when the disease is severe. This study also found that the p75 neurotrophin receptor was expressed in lumbar motor neurons in symptomatic SOD1-G93A mice and in motor neurons in the cervical spinal cords of patients with ALS. CONCLUSIONS: The murine and human ALS data suggest that the p75 neurotrophin receptor may play a death-signalling role in the pathogenesis of motor neuron degeneration. The precise mechanism by which this receptor drives the apoptotic process, both in murine SOD1-G93A motor neuron degeneration and in human amyotrophic lateral sclerosis, remains to be determined. PMID- 11771769 TI - Are the El Escorial and Revised El Escorial criteria for ALS reproducible? A study of inter-observer agreement. AB - INTRODUCTION: For accurate diagnosis, inter-observer agreement of criteria is important. METHODS: Using case records, the reproducibility of the original and revised El Escorial diagnostic criteria for amyotrophic lateral sclerosis were tested in a consecutive series of people referred to the Scottish Motor Neuron Disease Register. RESULTS: Agreement between independent observers was similar (weighted kappa: 0.783, 95% CI 0.656 to 0.911 (original criteria), 0.681, 95% CI 0.485 to 0.878 (revised)). CONCLUSIONS: Serious errors are unlikely, but the revised criteria may be less reproducible as they include more diagnostic categories. Revisions of diagnostic criteria should be tested for reproducibility and validity prior to widespread adoption. PMID- 11771770 TI - The use of non-invasive positive pressure ventilation (NIPPV) in ALS patients. A need for improved determination of intervention timing. AB - We present our experience with 27 patients with symptoms of alveolar hypoventilation, a precursor to respiratory failure, to demonstrate variability in symptoms, physiologic status and outcome of intervention. They represent 27 consecutive patients who tolerated NIPPV for more that 4 hours per 24-h period for more than 2 weeks. All patients received neurological consultation, electromyography and met criteria for ALS according to El Escorial diagnostic criteria. To assess respiratory status, spirometry was measured in sitting and when possible, in the supine positions. Resting arterial blood gases were available in 22 patients. Orthopnea was the most common symptom at the time of institution of NIPPV. No correlation existed between age at institution of NIPPV, duration of effective use of this technology or vital capacity and duration of effective use of NIPPV. The lack of correlation between vital capacity at the institution of NIPPV and duration of its effectiveness suggest that more sensitive indicators for the onset of alveolar hypoventilation must be defined, particularly since the principal benefit from its use is relief of symptoms of alveolar hypoventilation. PMID- 11771771 TI - Electrophysiologic evaluation of upper motor neuron involvement in amyotrophic lateral sclerosis. AB - BACKGROUND: The demonstration of upper motor neuron (UMN) dysfunction in patients with amyotrophic lateral sclerosis (ALS) with predominantly lower motor neuron (LMN) signs is clinically sometimes difficult. METHODS: We analyzed the possible role of F and H waves in the diagnosis of UMN dysfunction in 36 patients with different clinical forms of ALS and 20 controls. In both lower limbs we evaluated F-wave persistence and the F/M ratio of tibial nerves, Hmax/Mmax ratio, vibratory and recurrent (paired) inhibition of the H-reflex. RESULTS: The persistence of the F-response was decreased significantly in the LMN group only. The F/M amplitude ratio, vibrated-H/rest-H amplitude ratio and conditioned H/rest H amplitude ratio were significantly increased in patients with predominantly UMN, as well as in those with predominantly LMN signs. H/M amplitude ratios did not differ between the various patient groups. CONCLUSION: These findings show that ALS patients, including those without clinical evidence of UMN involvement, have a marked disinhibition of anterior horn motor neurons. The simple tests described could support an UMN abnormality when clinical signs are lacking, and help to establish a diagnosis sooner and more accurately. PMID- 11771772 TI - The Rilutek (riluzole) Global Early Access Programme: an open-label safety evaluation in the treatment of amyotrophic lateral sclerosis. AB - OBJECTIVES: This study had two main objectives: 1. To enable patients with amyotrophic lateral sclerosis (ALS) who had not participated in previous riluzole trials to receive riluzole therapy, and 2. To expand safety experience with the drug in a broad patient population. METHODS: This was a Phase IIIb multicentre, multinational, open-label, uncontrolled single treatment study of riluzole. Patients with diagnosed possible or probable ALS were administered 100 mg of riluzole/day (50 mg b.i.d.). Clinical and laboratory adverse events were recorded every month for the first 3 months and thereafter at 3-monthly intervals. RESULTS: 8383 patients from 44 countries were entered into the study; 7916 of these patients with recorded data were administered the study drug. The mean duration of riluzole treatment was 202.1 days, with a range of 1-630 days. The most frequently reported serious and non-serious adverse events were common symptoms of ALS (respiratory symptoms and dysphagia), and only 1.9% of serious adverse events were considered to be related to the study drug. CONCLUSIONS: The safety results with this broad population (over 10% of the estimated ALS population worldwide) were consistent with those previously reported from placebo controlled trials. No increase in adverse events and no unexpected adverse events were observed. PMID- 11771773 TI - Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) may be viewed as a paradigmatic disease for palliative care in neurodegenerative disorders. However, standards of care for ALS are known anecdotally to differ between and even within countries. METHOD: A survey was conducted among the members of the European ALS Study Group on standards of palliative care in the clinical management of patients with ALS and their families, by means of a questionnaire of 111 questions in the following areas: giving the diagnosis, treatment of symptoms, nutrition, community services, respiratory support, and terminal care. Of 110 questionnaires sent out, 73 (66%) were completed and returned from 18 countries, including all major ALS centres in Europe. RESULTS: The main areas of consensus included: presenting the diagnosis in the presence of a relative (85%) and offering a short-term follow-up (90%), regular weight checks (82%), availability of percutaneous endoscopic gastrostomy (PEG) (94%), and discussion of respiratory issues (90%). The main differences between centres concerned symptomatic drug treatment, availability of services, ventilation and terminal care. An additional survey shows considerable interest by the centres in palliative care trials. CONCLUSION: Great efforts are made by the centres to offer the best possible palliative care to ALS patients. The discrepancies in the type of care offered might be resolved by adopting common standards, on the basis of available evidence and mutual consensus. Several areas of ALS patient care would benefit from controlled studies to establish an evidence base for treatment decisions. PMID- 11771774 TI - Conjugal amyotrophic lateral sclerosis: suggestion for the implication of environmental factors. PMID- 11771775 TI - Virulence of Mycobacterium tuberculosis affects interleukin-8, monocyte chemoattractant protein-1 and interleukin-10 production by human mononuclear phagocytes. AB - Microbial virulence and cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of the pathogenesis of human tuberculosis. To determine the interrelationship between mycobacterial virulence and cytokine induction, human monocytes and monocyte-derived macrophages were infected with attenuated (H37Ra) and virulent (H37Rv and CH306) strains of M. tuberculosis and the amount of proinflammatory [interleukin (IL)-8 and monocyte chemoattractant protein (MCP)- 1] and inhibitory (IL- 10) cytokines was measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA). Infection with live bacilli induced de novo synthesis of IL-8, MCP-1 and IL-10, since cytokine release was abolished when cells were preincubated with the protein synthesis inhibitor cycloheximide. A differential production of antiinflammatory and inhibitory cytokines was observed. The amount of IL-8 and MCP-1 release was inversely related to strain virulence, the attenuated H37Ra strain being more prone than virulent strains to induce secretion of chemokines. In contrast, virulent strains induced greater amounts of the inhibitory cytokine IL-10. Efficient upregulation of IL-10 synthesis, but not of chemokines, required infection of cells with live bacilli, since heat killing of organisms or challenge with soluble mycobacterial products completely abrogated the effect. Moreover, cells infected with virulent strains produced IL-10 even at a very low bacillus-to-cell ratio and secreted IL-10 continuously during the 96 h that followed infection. The results suggest that the degree of virulence affects host cell responses to M. tuberculosis infection. Continued production of IL-10 may be one of the means by which M. tuberculosis downregulates acute local inflammatory reactions, favoring the development of tuberculosis. PMID- 11771776 TI - Regulation of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: role of vitamin E. AB - Skin plays an important role in protection against oxidative stressors such as ultraviolet radiation, ozone and chemicals. Chronic sun exposure causes degenerative changes in the skin that are recognized as photoaging. Oxidative stress has been shown to alter the expression of mammalian antioxidant enzymes as well as to enhance numerous transcription factors, including nuclear factor kappaB, stress-activated protein kinase and heat shock factor This latter is the transcription factor for the synthesis of heat shock proteins, which have been known to protect against a wide variety of toxic conditions, including extreme temperatures, oxidative stress and cytotoxic drugs. In this study we investigated the role of oxidative stress in the induction of heat shock protein (HSP) 70 in human skin fibroblasts and the effect of vitamin E. We found that significant HSP70 induction occurred after exposure to HOOH and that this was associated with a significant perturbation in protein and nonprotein sulfhydryl groups, and with a significant increase in protein carbonyl levels. Treatment with vitamin E conferred significant protection against stress-induced modifications of cellular sulfhydryl and carbonyl content, while maintaining functional levels of cytoprotective HSP70. Our results point to the possible involvement of redox mechanisms in the heat shock signal transduction pathway, which may play an important regulatory role in the genetic mechanisms of tolerance to oxidative stress. Exogenous antioxidant supplementation with vitamin E could have cosmetic benefits and may be an efficient tool to mitigate the consequences of free radical-induced skin damage. PMID- 11771777 TI - Cellular immunity in pediatric uveitis. AB - To evaluate cellular immunity in children with uveitis, we used the flow cytometry method to study the T lymphocyte subpopulation in peripheral blood. Cytometric analysis of peripheral blood lymphocytes using fluorochrome-marked monoclonal antibodies was carried out in 29 children aged 6-18 years with parasitic uveitis (group A) and with uveitis of another etiology (group B). The control group consisted of 28 healthy children aged 6-15 years. A substantially higher percentage of B lymphocytes (19.0 +/- 6.03) was observed in the children with parasitic uveitis than was observed in the healthy children. Moreover, the absolute values were higher in groups A (1.60 +/- 0.53) and B (1.81 +/- 0.40) than in controls (1.50 +/- 0.38). The lowest percentage of CD4+ lymphocytes (34.25 +/- 6.06) and the highest percentage of CD8+ lymphocytes (31.14 +/- 6.50) was found in children with parasitic uveitis. The lowest index CD4+/CD8+ (1.29 +/ 0.53) in the group of children with parasitic uveitis reflected severe disorders in response regulation. However, the percentage values of natural killer cells was lower in the two groups of patients than in controls. These results suggest that quantitative changes in the subpopulation of peripheral blood lymphocytes are more pronounced in parasitic uveitis. PMID- 11771778 TI - Increased demand for steroid therapy in hyperprolactinemic patients with rheumatoid arthritis. AB - The role of increased plasma prolactin (PRL) in rheumatoid arthritis (RA) is not fully explained. The aim of this study was to compare the clinical features and the treatment administered in RA patients with normal and elevated plasma PRL concentrations. Forty-nine patients with rheumatoid arthritis and 16 healthy subjects were included in this study In healthy controls, PRL concentrations were 7.6 micro/l (median), in 34 patients plasma PRL was less than 20 micro/l (9.9 micro/l) and in 15 patients it was elevated, with a median of 26.7 micro/l. No differences in clinical features were found compared with normal or increased plasma PRL. The introduction of corticoid therapy produced a significant difference. Steroid therapy was administered to 93% of the patients with hyperprolactinemia, compared with 59% of those with normal PRL concentrations. Daily prednisone doses higher than 5 mg were administered to 43% of the patients with elevated PRL, compared with 25% of patients with normal prolactin concentrations. In conclusion, the clinical feature of patients with rheumatoid arthritis did not differ in subjects with elevated PRL concentrations and in those with normal concentrations. The difference between these two groups was in the higher demand for steroid therapy in patients with hyperprolactinemia. PMID- 11771779 TI - Postoperative physiopathological analysis of inflammatory parameters in patients undergoing hip or knee arthroplasty. AB - Infection after total hip or knee arthroplasty is a major concern for the orthopedic surgeon. Because postoperative recovery in patients undergoing hip or knee replacement is always characterized by a shift in basal laboratory parameters, the value of the routine use of these parameters in the detection of this major complication is controversial. The aim of this study was to evaluate the physiological behavior of these parameters, the most reliable of which are C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC). The pattern of these parameters was observed for 60 days after surgery in 74 patients (48 males and 26 females) who underwent total hip or total knee arthroplasty. Mean age was 65.4 years. ESR reached a peak on day 5 and then decreased as much as 3-fold by day 60. CRP displayed even greater sensitivity with a peak level on day 3 followed by a rapid return to basal levels. WBC also peaked on day 1. No significant differences were found between total hip arthroplasty and total knee arthroplasty. Observation of the pattern of these parameters identifies any nonphysiological modifications and enables suitable measures to be adopted. PMID- 11771780 TI - Effect of reverse curve mushroom archwire on lower incisors in adult patients: a prospective study. AB - This prospective clinical study was undertaken to analyze adult skeletodental changes induced by a reverse curve mushroom archwire during the initial stage of treatment. Lateral cephalograms from before treatment and immediately after bite opening were evaluated from 8 female adult patients who were undergoing lingual orthodontic treatment. Before treatment the patients had a mean overbite of 3.9 mm. Six linear and 5 angular measurements were selected for cephalometric analysis. The mean change in the cephalometric parameters was subjected to paired t-tests to determine whether the change was significant. There was a highly significant overbite reduction (-1.9 mm, P < .001) leaving a postintrusion overbite of 2.0 mm. The lower incisors were intruded 1.5 mm (P < .001) and the lower incisor edge was in an approximately stable sagittal position (L1 to NPg = 0.2 mm, NS). Some lower incisor proclination (L1 to MP = 1.2 degrees) was seen, which was not of significance. The mandibular molars were not significantly extruded. After bite opening the mandibular plane angle was not significantly altered. Consequently, the lower anterior face height was not significantly increased. The results of this study revealed that the use of reverse curve mushroom archwire is capable of intruding the lower incisors with minimal side effects on the posterior teeth. PMID- 11771781 TI - Effects of patient age and sex on treatment: correction of Class II malocclusion with the Begg technique. AB - When children are treated orthodontically during a phase of active growth-notably adolescence-there is the opportunity to harness growth to achieve some of the correction, especially in the sagittal plane in which differential jaw growth can harmonize dental relationships. All correction must be from tooth movement when there is no growth. Three questions were addressed in the present study: (1) how much orthodontic correction is achieved by bone growth? (2) do the proportions of tooth and bone movement depend on patient age? and (3) do the jaws of boys and girls grow at discernibly different rates during treatment? A sample of 139 children aged 9 to 17 years at the start of treatment with Class II division 1 malocclusions was studied cephalometrically using Johnston analysis. Maxillary and mandibular growth were highest in the youngest children, with rates decreasing to effectively zero in the oldest adolescents. Means adjusted for age were significantly higher for boys than for girls for upper and lower jaw growth. Age had little influence on the amount of tooth movement except for a marked decline with age in the mesial movement of the maxillary first molar, which was greatest in the youngest patients of both sexes. The amount of orthodontic correction was independent of age, but in the youngest quartile of the sample, most of the correction (87%) was due to differential jaw growth in the youngest quartile of the sample, and the rest (13%) resulted from tooth movement, whereas in the oldest quartile, most of the correction was due to tooth movement (64% tooth movement and 36% bone growth). Overall, the influence of age and sex had significant influences on multiple skeletodental variables, suggesting that research designs need to account for these demographic sources of variability. Although all cases were treated to a Class I occlusion, the nature of the correction was affected measurably by the patient's age and sex. PMID- 11771782 TI - The effect of vertical and horizontal head positioning in panoramic radiography on mesiodistal tooth angulations. AB - The purposes of this study were to examine the effect of potentially common patient positioning errors in panoramic radiography on imaged mesiodistal tooth angulations and to compare these results with the imaged mesiodistal tooth angulations present at an idealized head position. A human skull served as the matrix into which a constructed typodont testing device was fixed according to anteroposterior and vertical cephalometric normals. The skull was then repeatedly imaged and repositioned five times at each of the following five head positions: ideal head position, 5 degrees right, 5 degrees left, 5 degrees up, and 5 degrees down. The images were scanned and digitized with custom software to determine the image mesiodistal tooth angulations. Results revealed that the majority of image angles from the five head positions were statistically significantly different than image angles from the idealized head position. Maxillary teeth were more sensitive to 5 degrees up/down head rotation, with 5 degrees up causing mesial projection and 5 degrees down causing distal projection of maxillary roots. Mandibular anterior teeth were more sensitive to 5 degrees right/left head rotation, with the projected mesiodistal angular difference between 5 degrees right and 5 degrees left rotation ranging from 4.0 degrees to 22.3 degrees. Maxillary teeth were relatively unaffected by 5 degrees right/left head rotation, and mandibular teeth were relatively unaffected by 5 degrees up/down head rotation. It was concluded that the clinical assessment of mesiodistal tooth angulation with panoramic radiography should be approached with extreme caution with an understanding of the inherent image distortions that can be further complicated by the potential for aberrant head positioning. PMID- 11771783 TI - Occlusal side effects caused by a mandibular advancement appliance in patients with obstructive sleep apnea. AB - Mandibular advancement appliances (MAA) have been established as an alternative treatment option for obstructive sleep apnea (OSA). Although the therapeutic effect of these devices has been proven both clinically and polysomnographically through various studies, there are very few follow-up examinations in existence concerning possible dental side effects caused by the MAA. However, if lifelong treatment of OSA is considered, these follow-up examinations are of utmost importance. This article presents 2 cases with unexpected dental side effects and occlusal alterations caused by MAA therapy. PMID- 11771784 TI - Evaluation of nonrinse conditioning solution and a compomer as an alternative method of bonding orthodontic bracket. AB - Damage to the enamel surface during bonding and debonding of orthodontic brackets is a clinical concern. Alternative bonding methods that minimize enamel surface damage while maintaining a clinically useful bond strength are an aim of current research. The purpose of this study was to compare the effects of using two enamel conditioners and adhesives on the shear bond strength and bracket failure location. Forty freshly extracted human molars were pumiced and randomly divided into two groups of 20 teeth. Metal orthodontic brackets were bonded to the enamel surface by one of two protocols: 37% phosphoric acid with a composite adhesive (Transbond XT) or a nonrinse conditioner with a compomer adhesive (Dyract flow). The teeth were mounted in phenolic rings and stored in deionized water at 37 degrees C for 24 hours. A Zwick Universal Testing Machine was used to determine shear bond strengths in MegaPascals. The residual adhesive on the enamel surface was evaluated using the Adhesive Remnant Index. Student t-test and chi2-test were used to compare the two groups. Significance was predetermined at P < or = .05. The results of the t-tests indicated that there were significant differences between the two adhesive systems (t = 11.18 and P = .001) with the nonrinse conditioner/compomer system having lower shear bond strength (X = 1.7 +/- 0.9 MPa) than the phosphoric acid/composite adhesive (X = 10.4 +/- 2.8 MPa). The results of the Chi Square test evaluating the residual adhesives on the enamel surfaces also revealed significant differences between the two groups (chi2 = 7.62, P = .022). In conclusion, a nonrinse conditioner used with a compomer adhesive had significantly lower shear bond strength than a phosphoric acid/composite adhesive system. PMID- 11771785 TI - Effect of using a new cyanoacrylate adhesive on the shear bond strength of orthodontic brackets. AB - During bonding of orthodontic brackets to enamel, conventional adhesive systems use three different agents: an enamel conditioner, a primer solution, and an adhesive resin. A unique characteristic of some new bonding systems is that they need neither a priming agent nor a curing light to bond brackets. Such an approach should be more cost-effective for the clinician and indirectly also for the patient. The purpose of this study was to determine the effects of using a cyanoacrylate adhesive on the shear bond strength of orthodontic brackets and on the bracket/adhesive failure mode. The brackets were bonded to extracted human teeth according to one of two protocols. Group 1: Teeth were etched with 37% phosphoric acid. After applying the primer, the brackets were bonded with Transbond XT (3M Unitek, Monrovia, Calif) and were light-cured for 20 seconds. Group 2: Teeth were etched with 35% phosphoric acid. The brackets were then bonded with Smartbond (Gestenco International, Gothenburg, Sweden). The present in vitro findings indicated that the use of the cyanoacrylate adhesive to bond orthodontic brackets to the enamel surface did not result in a significantly different (P = .24) shear bond force (mean = 5.8 +/- 2.4 MPa) as compared to the control group (mean = 5.2 +/- 2.9 MPa). The comparison of the Adhesive Remnant Index scores indicated that there was significantly (P = .006) less residual adhesive remaining on the tooth with the cyanoacrylate than on the tooth with the conventional adhesive system. In conclusion, the new adhesive has the potential to be used to bond orthodontic brackets while reducing the total bonding time. PMID- 11771786 TI - A clinical retrospective evaluation of 2 orthodontic band cements. AB - This study aimed to compare the time to first failure of stainless steel orthodontic first permanent molar bands cemented with either a modified composite (Band-Lok, Reliance Orthodontic Products) or a conventional glass ionomer cement (AquaCem, De Trey Dentsply). The effect of patient sex, patient age at the start of treatment, the presenting malocclusion, treatment mechanics, and the operator proficiency on band survival was also assessed. Data for 219 bands cemented with Band-Lok in 108 patients and for 395 bands cemented with AquaCem in 183 patients were analyzed. For each case, a single molar band, either the band that was first to fail or the band that had the shortest follow-up time, was chosen for analysis. For each cement, whether headgear was used or not, there was no significant difference in time to first band failure (P = .398). Twenty-six percent of patients had at least one band failure with Band-Lok, and 30% of patients had at least one band failure with AquaCem, representing an 18% band failure rate for each cement. There was no significant difference in time to first band failure for either cement with respect to sex of the patient (P = .842), patient age at the start of treatment (P = .257), presenting malocclusion (P = .319), or operator proficiency (P = .062). The use of headgear, however, reduced significantly the time to first band failure irrespective of cement type (P = .0069). Headgear use was identified as a predictor of first permanent molar band survival. Clinical performance of bands cemented with either cement appears to be similar and was influenced significantly by the use of headgear. PMID- 11771787 TI - Reduction of the hypocone of the maxillary first molar and Class III malocclusion. AB - This study was conducted to examine the incidence of evolutionary changes of the maxillary molars in orthodontic patients and to investigate the association of this event with craniofacial growth. Among 4,892 Japanese patients treated at the orthodontic clinic of Hiroshima University Dental Hospital, 59 patients presented with a defect of the distolingual cusp of the maxillary first molar. They consisted of 52 female patients and seven male patients with a mean age of 14.7 years. Eruption of the maxillary first and second molars was delayed and the third molar was congenitally missing in all of these patients. Thirty-seven patients exhibited Class III malocclusion (Class III evolution group). The Z scores of cephalometric measurements were compared between the Class III evolution group and the Class III control group. The latter group consisted of 37 Class III subjects with no evolutionary dental anomalies and no orthodontic history. The tooth developmental score (TDS) for each age at the initial record was compared with Nolla's standard tooth developmental score (STDS) for equivalent ages using paired t-tests. The Z scores for Ptm'-A and Ar-A were significantly smaller in the Class III evolutionary group than in the Class III control group (P < .05). The TDS for the maxillary first and second molars were significantly smaller than the STDS for these molars (P < .01). The TDS for the maxillary second molar was significantly larger than the STDS for the maxillary third molar (P < .01). This study revealed that an evolution change of the maxillary molar is more common (P < .05) in female patients than in male patients, is more frequent (P < .05) in subjects with Class III malocclusion, and is related to the anteroposterior undergrowth of the maxilla. PMID- 11771788 TI - Growth hormone receptor and IGF-I receptor immunoreactivity during orthodontic tooth movement in the prednisolone-treated rat. AB - Bone remodeling during tooth movement is regulated by local and systemic factors. Two regulators of bone metabolism are growth hormone (GH) and insulin-like growth factor-I (IGF-I). Their effects are mediated via binding to GH receptor (GHR) and IGF-I receptor (IGF-IR) in target tissues. Corticosteroids may affect the activity of these growth factors. This study examined the effect of prednisolone on GHR and IGF-IR expression in dental tissues following orthodontic tooth movement. The corticosteroid-treated group (N = 6) was administered prednisolone (1 mg/kg) daily and the control group (N = 6) received equivalent volumes of saline. An orthodontic force (30 g) was applied to the maxillary first molar. Animals were sacrificed 12 days postappliance insertion. Sagittal sections of the first molar were stained for GHR and IGF-IR immunoreactivity. GHR and IGF-IR cell counts were elevated following appliance-treatment. Orthodontic tooth movement appeared to up-regulate GHR and IGF-IR immunoreactivity, but this up-regulation was reduced following prednisolone treatment. The suppression of GHR and IGF-I immunoreactivity in steroid-treated animals infers the mechanism whereby bone resorption and deposition, necessary for orthodontic tooth movement, may be inhibited by prednisolone. However, at 12 days postappliance insertion, no difference in orthodontic tooth movement was observed following low-dose prednisolone treatment. PMID- 11771789 TI - The effect of chronic renal insufficiency on orthodontic tooth movement in rats. AB - The purpose of this study was to determine the effects of impaired renal function on the amount of orthodontic tooth movement (OTM) in a rat model of renal insufficiency (RI). The animals were divided into three groups: a control unoperated group in which only OTM was done, a sham-operated group, and an RI group. OTM was done two weeks after performance of the sham operation or the surgery to induce RI. Renal failure was induced by electrocoagulation of one kidney cortex followed by contralateral nephrectomy. A fixed orthodontic appliance consisting of a 5 mm length of nickel-titanium closed-coil spring was ligated between the maxillary right incisor and first molar to deliver an initial mesial force of 60 g. Four weeks after RI induction, the amount of tooth movement was estimated by measuring the space created between the first and second molars on a stone cast. Bone density was measured by optical densitometry on radiographs and serum parathyroid hormone (PTH) was measured with a radioimmunoassay method. The results showed that induction of RI significantly increased both OTM (P < .05) and PTH levels (P < .01), although there was no significant difference in bone density by optical densitometry between the unoperated, sham-operated, and RI groups four weeks after RI induction. The results suggest that an increase of bone-remodeling activities, as evident from a significantly higher level of PTH, may be responsible for increase in tooth movement. PMID- 11771790 TI - A morphometric study with setup models for bracket design. AB - This study was designed to obtain basic data on bracket design for the Asian patient. Setup models of 125 Japanese orthodontic patients seeking treatment were measured relative to the occlusal plane by the Andrews' method. A single experienced dental technician fabricated all setup models to provide one-tooth-to two-teeth occlusal relationship, maximum intercuspation, ABC contacts, flat occlusal planes, canine guidance, and anterior guidance. Means and standard deviations of the crown angulations, inclinations, facial prominence, vertical contour, horizontal contour, and maxillary molar offsets were measured to reach the following conclusions: (1) No difference was observed in crown angulation between groups with one-tooth-to-two-teeth relationships. (2) Crown inclinations of the mandibular central and lateral incisors and canine were greater in the Class II setup group. (3) Maxillary molar offset averaged approximately 7 degrees in the Class II setup group. (4) The data from the Class I setup group showed minor differences from other researchers' data. PMID- 11771791 TI - The Edward H. Angle Society of Orthodontists 2001: a North American or an international society? PMID- 11771792 TI - What we know about gun use among adolescents. AB - The current generation of American teenagers has grown up surrounded by gun violence. Guns have played a significant role in shaping the developmental trajectories and behaviors of many inner-city youths. In this essay, we examine the role of guns in the lives of young people, and especially in the social and symbolic construction of violent events among adolescents, primarily focusing on males. First, we review studies of gun attitudes and behaviors as well as several epidemiological studies of firearm experiences and risk factors for violence among youth. Second, we summarize several recent studies on the trends in youth violence in relation to firearms. Next, we review findings from our original research based on in-depth interviews with 377 active gun offenders from two socially isolated inner-city neighborhoods. We present descriptive counts for the sample on variables relating to gun acquisition and use. Data on the use of guns in violent events among adolescents are generally lacking in prior research. We attempt to fill that knowledge gap by presenting a summary of our more detailed analysis of gun and nongun use in violent events reported by our respondents. PMID- 11771793 TI - African American single mothers and children in context: a review of studies on risk and resilience. AB - This paper presents a comprehensive review of research linking single-parent family structure to parenting processes, maternal well-being, and child developmental outcomes among African Americans. The approaches used to study these families, related methodological and conceptual concerns, and the factors linked to maternal well-being, effective parenting processes, family functioning, and child outcomes are addressed. Much work remains to be done on conceptualizing and assessing parenting processes among African Americans in general and single African American mothers in particular. Researchers must examine more carefully the circumstances that foster or impede successful parenting among these mothers. Studies also are needed to disentangle the interactions between economic stress and parenting behavior and to determine the extent to which the findings can be applied to middle-income single African American parents. PMID- 11771794 TI - Children's testimony: a review of research on memory for past experiences. AB - This review of children's testimony focuses on research related to memory for past experiences. The aspects of the memory system that are involved in testimony are discussed and the development of autobiographical memory is examined. Relevant research findings are summarized in the context of an information processing model of memory and the implications of this work for clinical practice are outlined. We conclude that (1) under certain conditions, even very young children can remember and report past experiences with some accuracy over very long periods of time; (2) substantial and significant developmental differences have been demonstrated in children's abilities to provide eyewitness testimony; (3) children can be influenced in a variety of ways to provide complete and elaborated reports of events that never occurred; and (4) even experts cannot always tell the difference between true and false reports. PMID- 11771796 TI - Thanksgiving. PMID- 11771797 TI - Athletic stress fractures: part II. The lower body. Part III. The upper body- with a section on the female athlete. AB - Part I of this article (published in the November issue) focused on the history, epidemiology, physiology, risk factors, radiography, diagnosis, and treatment of stress fractures. Part II reviews the specifics of stress fractures involving the lower body, the upper body, and includes a special section on the female athlete. PMID- 11771795 TI - Examining partner and child abuse: are we ready for a more integrated approach to family violence? AB - Research and treatment for partner abuse and child abuse are relatively distinct enterprises, yet when the theoretical and research literatures related to these two forms of family violence are examined together, the likelihood of meaningful associations is strikingly apparent. Partner abuse and child abuse co-occur more often than one might expect by chance, and in the context of overlapping theories and risk factors, this suggests that a more integrated conceptualization might be fruitful. We summarize and provide a framework for describing the large number of similar predictors of partner and child abuse, identify some potentially interesting dyadic differences, comment on how our research methodologies could address an integrated area of family violence, and suggest some directions for future research and treatment. PMID- 11771798 TI - Patient factors affecting autologous and allogeneic blood transfusion rates in total hip arthroplasty. AB - Factors that place patients undergoing total hip arthroplasty (THA) at increased risk of receiving an allogeneic or autologous blood transfusion may aid in determining which patients should predonate blood. The records of 354 consecutive patients undergoing THA were retrospectively reviewed to determine patient factors related to transfusion requirement. The risk of transfusion requirement was most strongly correlated with low preoperative hemoglobin level, but also with older age, higher American Society of Anesthesiologists physical status rating, female sex, cemented arthroplasty, and revision surgery. These patients were also least likely to predonate blood, likely because of their comorbid status. PMID- 11771800 TI - Freiberg's infraction. PMID- 11771799 TI - Vertebral sarcoidosis of the spine in a football player. AB - Osseous involvement is common in sarcoidosis, but most cases of osseous sarcoidosis occur in the long bones of the hands and feet. Vertebral involvement in sarcoidosis is rare. A case of vertebral sarcoidosis in a 19-year-old male football player is presented. The patient had clinical, radiologic, laboratory, and pathologic findings consistent with a case of vertebral sarcoidosis. A review of the literature on sarcoid involvement of the spine is also presented. Although rare, sarcoid infiltration of the vertebrae is a recognized entity. Magnetic resonance imaging can be helpful in making the diagnosis, but biopsy is needed for confirmation. PMID- 11771801 TI - Overcoming truth telling as an obstacle to initiating safer sex: clients and health practitioners planning deception during HIV test counseling. AB - This article considers how deception, as a strategy for handling delicate interpersonal situations, is raised and responded to during HIV pretest counseling sessions. Two cases are presented in which clients (CLs) formulate extrarelational sexual encounters as potential obstacles to initiating safer sex practices with long-term relational partners (because reinitiating safer sex with such partners would entail admission of the extrarelational encounters). Close analysis of spoken interaction reveals that CLs display their resistance to initiating safer sex by animating, through hypothetical dialogue, their long-term partners' requests for explanation of the disruption in their usual intimate behaviors; health practitioners attempt to overcome this obstacle of "truth telling" by suggesting deception in its place. This study extends current understandings of the formulation and planning of deceptive messages in the course of actual health promotion interactions. The implications of this investigation suggest that deception may pose a viable, albeit controversial, option when promoting disease prevention behaviors, especially in delicate interpersonal interactions such as not wanting to admit an extrarelational affair. PMID- 11771802 TI - Toward a better death: applying Burkean principles of symbolic action to interpret family adaptation to Karen Ann Quinlan's coma. AB - This article considers the manner that families come to accept the collapse of identity in a family member who has entered a medical crisis with no hope of returning from it. The transformation is regarded as a "right of passage" and is characterized in terms of both the conditions that bring about resistance to the passage as well as the sorts of symbolic activities that ultimately allow the transformation to occur. The theoretical source that is used to discuss both these issues is Kenneth Burke's (1969) theory of Dramatism, regarded herein as a template that guides both interpersonal action and experience. The primary text used to illustrate these points is the story of Karen Ann Quinlan, a young woman who fell into persistent vegetative state in 1975, as told by her parents. A general goal of this article is to illustrate some of the characteristics of Dramatism as a theory of interpersonal action, especially after the collapse of routine. More particularly, it is hoped that the analysis will aid health professionals in sense making and interacting with families in crisis. PMID- 11771803 TI - Media, audience, and policy perspectives in health broadcasting. AB - Effective coordination between service delivery systems and communication networks is essential for the success of development programs. This becomes particularly crucial when the number of agencies involved is large and they are not working under 1 authority. Information needs of the community are another major concern. This article attempts to assess the extent of convergence between electronic media, government policy, and the targeted audience on the coverage of health topics. The Indian state of Andhra Pradesh was chosen as the field. The study adopts a mix of both quantitative and qualitative techniques. The findings reveal limited convergence, indicating the need for more effective reflection of the policy guidelines into media programs. PMID- 11771804 TI - Technology as the representative anecdote in popular discourses of health and medicine. AB - Using a Burkean framework (1969), this article approaches medical dramas as cultural texts to be read for dominant meanings of health and health care. Burke's representative anecdote illuminates the melding of science, technology, and healing in popular discourses of health, establishing technological intervention as the norm and marginalizing nontechnological (i.e., alternative) forms of health care. Popular entertainment reinforces this anecdote in narratives of healing as technological competence triumphing over nature. PMID- 11771805 TI - Finding the meanings of college drinking: an analysis of fraternity drinking stories. AB - College drinking has traditionally been studied from a public health perspective that attempts to quantify behavior as a means toward description, explanation, and intervention. This article offers a critical and cultural approach to understanding the meanings and functions of high-risk drinking and the ways in which those meanings are reproduced within the culture. Data were collected via an ethnographic study of fraternity members at a large midwestern university to explore the communication of excessive drinking norms. Viewed from various narrative and structural theories, the study examines collected drinking stories as a source for analyzing the construction of meanings surrounding drunkenness for the fraternity subculture. Five themes emerged as functions of drunkenness for the culture. Implications for prevention are discussed. PMID- 11771806 TI - Intercultural communication between patients and health care providers: an exploration of intercultural communication effectiveness, cultural sensitivity, stress, and anxiety. AB - Cultural diversity is becoming increasingly more important in the workplace. This is particularly true in health care organizations facing demographic shifts in the patients served and their families. This study serves to aid the development of intercultural communication training programs for health care providers by examining how cultural sensitivity and effective intercultural communication, besides helping patients, personally benefit health care providers by reducing their stress. Effective intercultural communication and cultural sensitivity were found to be related. Health care providers' levels of intercultural anxiety also were found to correlate with effective intercultural communication. PMID- 11771807 TI - Development of a Swedish version of the Adolescent Coping Orientation for Problem Experiences (A-Cope). AB - The objective was to investigate the psychometric properties of the Adolescent Coping Orientation for Problem Experiences (A-Cope) among Swedish adolescent girls. A sample of 590 13- and 15-year old girls participated. The original version of the A-Cope failed to demonstrate an adequate factor structure. A revised version was developed (A-Cope-S), consisting of 28 items forming 6 subscales with moderate to acceptable homogeneity. The findings suggest that the A-Cope-S is suitable for the study of coping among Swedish adolescent girls. PMID- 11771808 TI - The circumplex structure of affect: a Swedish version. AB - The taxonomy of a circumplex model has been widely applied in the emotion domain and especially by researchers advocating a systematic arrangement of conscious emotional experience (see Fabrigar, Visser & Browne, 1997; Feldman Barett & Russell, 1999 for recent reviews). To rule out some of the lexical problems in the naming of affective states in the circumplex space, Larsen and Diener (1992) suggested a labeling system with forty-eight English adjectives representing eight affective states. The objective of the present study was to examine how well Swedish adjectives map onto a dimensional model of this kind, in doing so, to compose a Swedish measure for self-reported affect. The forty-eight Swedish adjectives translated from Larsen and Diener (1992) failed to capture a pure circumplex structure. However, when approximately two thirds of these adjectives were reanalyzed, a reasonable consistency with the circumplex model was reached. This suggested a composite Swedish measure for self-rated affect, with up to four adjectives representing each of the eight affective states in the circumplex space. PMID- 11771809 TI - PLS model building: a multivariate approach to personality test data. AB - The aim of this study was to demonstrate how personality test data can be plotted with a multivariate method known as Partial Least Squares of Latent Structures (PLS). The basic methodology behind PLS modeling is presented and the example demonstrates how a PLS model of personality test data can be used for diagnostic prediction. Principles for validating the models are also presented. The conclusion is that PLS modeling appears to be a powerful method for extracting clinically relevant information from complex personality test data matrixes. It could be used as a complement to more hard modeling methods in the process of examining a new area of interest. PMID- 11771810 TI - Validation of an ipsative personality measure (DISCUS). AB - The purpose of this study was to examine the construct validity of an ipsative personality test (DISCUS), and various effects of the ipsative format of the test. Both an ipsative and a normative version of the DISCUS test was administered to a sample of undergraduate students (N = 103), along with an adjective based personality test that measures the Big-Five personality traits (5PFa). The results indicated that the normative and the ipsative version of DISCUS are not equivalent, and caution is needed when using the ipsative version for psychometric evaluations as in validation studies. The four DISCUS dimensions (Dominance, Influence, Stability, and Carefulness) represented combinations of the Big-Five traits rather than independent traits as indicated by the correlations with the Big-Five measure. PMID- 11771811 TI - A Norwegian translation of the self-liking and competence scale. AB - Although global self-esteem has historically been assumed to be a unidimensional construct, recent theory and research has challenged this assumption. Instead, it has been suggested that self-esteem might more fruitfully be viewed as a two dimensional construct composed of: (a) self-liking, based on our perceptions of feedback from our social environment; and (b) self-competence, based on our internal conceptions of success and failure in performing tasks. The Self-Liking and Competence Scale (SLCS) is a self-esteem measure that has recently been developed based on this two-dimensional conceptualization of self-esteem. The purpose of the present research was to validate a Norwegian translation of the SLCS. 372 participants were given a translated version of the SLCS, and the translated scale exhibited psychometric properties similar to those of the original English version of the scale. PMID- 11771812 TI - Emotion recognition and social adjustment in school-aged girls and boys. AB - The present study investigated emotion recognition accuracy and its relation to social adjustment in 7-10 year-old children. The ability to recognize basic emotions from facial and vocal expressions was measured and compared to peer popularity and to teacher-rated social competence. The results showed that emotion recognition was related to these measures of social adjustment, but the gender of a child and emotion category affected this relationship. Emotion recognition accuracy was significantly related to social adjustment for the girls, but not for the boys. For the girls, especially the recognition of surprise was related to social adjustment. Together, these results suggest that the ability to recognize others' emotional states from nonverbal cues is an important socio-cognitive ability for school-aged girls. PMID- 11771813 TI - The relationship between cognitive abilities and maternal ratings of externalizing behaviors in preschool children. AB - The association between child cognitive abilities and maternal ratings of child externalizing behaviors was investigated in a randomly selected sample of 290 preschool children. Child cognitive abilities were assessed by the WPPSI-R, whereas mothers completed the Yale Children's Inventory for the assessment of child externalizing behaviors. Maternal education, and maternal child-rearing style, as defined by scores on the Child Rearing Practices Report, was significantly related to perceived externalizing child behavior. Hierarchical regression analyses revealed that for girls, low child IQ remained a significant predictor of perceived externalizing behavior when effects of maternal education and child-rearing style were controlled for (p < 0.01). Maternal child-rearing style made independent contributions to explaining variance in girls' and boys' behavior score. The results are discussed in terms of differential gender socialization practices and gender stereotypes. PMID- 11771814 TI - Post-traumatic stress disorder in patients with coronary artery disease: a review and evaluation of the risk. AB - Psychosocial factors are known to impact on the prognosis of patients with coronary artery disease independently of disease severity. However, few studies have looked at whether these patients are at risk of developing post-traumatic stress disorder, and the potential implications for morbidity and mortality. Through a review of the empirical literature, the objectives were to investigate whether patients with coronary artery disease are at risk of developing this disorder, to look at relations between post-traumatic stress disorder and heart disease, and to stimulate further research. The review indicated that some patients with coronary artery disease are at risk of developing post-traumatic stress disorder, although the prevalence varied considerably. Methodological issues together with recommendations for future research are discussed. Although only some cardiac patients may develop post-traumatic stress, this disorder should not be overlooked due to its potential role in reinfarctions and mortality. PMID- 11771815 TI - Obsessive-compulsive symptoms, white noise and intrusions of self-relevant negative thoughts in a thought suppression paradigm. AB - Forty female students participated in an experiment where they were asked to suppress a negative self-relevant thought. Half the group suppressed in a loud white noise condition (90 decibels) whereas the other half suppressed in a noise condition of much lower intensity (50 decibels). The subjects were divided up into two groups on the basis of their scores on the Obsessive Compulsive Thoughts Checklist (Bouvard, Cottraux, Mollard, Arthus, Lachance, Guerin, Sauteraud & Yao, 1997). It was predicted that 1) Subjects scoring high on obsessive-compulsive symptoms would show more intrusive thoughts 2) Loud noise would increase intrusive thoughts, especially for subjects scoring high on obsessive-compulsive symptoms. As expected subjects who scored high on obsessive-compulsive symptoms showed more intrusive thoughts, but contrary to expectations loud noise did not increase intrusive thoughts. In fact obsessive-compulsive symptoms were related to more intrusions in the condition of noise of less intensity but not in the condition of loud noise. Implications are discussed. PMID- 11771816 TI - Memory deficits in young schizophrenics with normal general intellectual function. AB - The aim of the present study was to examine different dimensions of memory functioning in young schizophrenics with normal general intellectual abilities. Thirty-three patients with schizophrenia and 33 healthy controls were included in the study. The results suggest that immediate short-term memory is intact, though there emerged a working memory deficit in the schizophrenia group. Deficient encoding of verbal material was observed in some, but not in other, testing conditions. There also seemed to be a retrieval deficit for verbal material in schizophrenia, though no storage deficit was indicated. Impaired memory for non verbal material was also revealed. These results occurred in a context of intact executive functioning as measured by the Wisconsin Card Sorting Test. The results indicate that temporal and frontal structures, as well as their interconnections, may be compromised in schizophrenia. PMID- 11771817 TI - Psychological characteristics of women with eating disorders: permanent or transient features? AB - The purpose of the study was to make a psychological profile of Danish women with Eating Disorders, who were not currently hospitalized. 75 women between the ages of 19 and 46 years participated. 22 participants suffered from a clinical eating disorder (ED). 20 women had previously suffered from a clinical ED, and 33 women had never suffered from ED. The study included sociodemographic data, problems in relation to eating and weight, exposure to stressful life events, and the following questionnaires: The Eating Disorder Inventory, the Rosenberg Self Esteem Scale, the Coping Styles Questionnaire, the Perceived Stress Scale, the Defense Style Questionnaire, and the Trauma Symptom Checklist. Psychologically, women with ED differed significantly from women without ED by using a more primitive defense style, perceiving themselves as being more exposed to stress, using more inefficient methods of coping and having lower self-esteem. Unexpectedly, the study also showed that recovery from an ED was resulting in normalisation of both behavioral and psychological characteristics. The implications of these findings are discussed. PMID- 11771818 TI - Vascular growth factor and gene therapy to induce new vessels in the ischemic myocardium. Therapeutic angiogenesis. PMID- 11771819 TI - Preservation of the endothelium in cardiovascular surgery-some practical suggestions--a review. PMID- 11771820 TI - Ruling out myocardial infarction with troponin T and creatine kinase MB mass: diagnostic and prognostic aspects. AB - OBJECTIVE: To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. DESIGN: The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. RESULTS: MI diagnosis was confirmed with elevated TnT (>0.10 microg/l) in 108 patients. in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (>5.0 microg/l). in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD (p < 0.001). CONCLUSION: Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis. PMID- 11771821 TI - Gender specific sympathetic and hemorrheological responses to mental stress in healthy young subjects. AB - OBJECTIVE: Activation of the sympathetic nervous system may increase hematocrit (Hct), whole blood viscosity (WBV), and possibly cardiovascular risk. The aim was to study gender specific differences of mental stress on sympathetic reactivity and blood rheology. METHODS: Responses in blood pressure, heart rate (HR), Hct, WBV (Bohlin rotational viscosimeter), and plasma catecholamines to a mental arithmetic stress test (MST) were measured in male (n = 10, 23 +/- 3 years, BMI 23 +/- 2 kg/m2) and female (n = 10, 21 +/- 4 years, BMI 24 +/- 2 kg/m2) students. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR increased during MST in men and women, and declined to baseline levels after 15 min of recovery. In men, plasma adrenaline increased by 217% during MST (p < 0.01, ANOVA). and plasma noradrenaline increased by 68% (p < 0.05). Hct and WBV at low shear rates (0.5 and 1.1 l/s) increased as well (p < 0.001, p < 0.05, and p < 0.05, respectively). In women, the increase in plasma adrenaline averaged 118% during MST (p < 0.05) while plasma noradrenaline (-3%, p = 0.38), Hct, and WBV at all shear rates remained unchanged. Men and women differed in A adrenaline (p < 0.05), A noradrenaline (p = 0.01), delta Hct (p < 0.05), and delta WBV (p < 0.05). A Hct tended to correlate with delta SBP (r= 0.60, p = 0.07), A DBP (r = 0.57. p = 0.09). and delta HR (r = 0.50, p = 0.14), and correlated significantly with A noradrenaline (r = 0.66, p < 0.05) in men only. Multiple regression analysis showed that gender independently explained 22% of the change in Hct during mental stress. CONCLUSION: Data suggest gender specific differences in sympathetic and hemorrheological responses to mental stress in healthy young subjects. In men, sympathetic responses were related to hemorrheological responses, but not in women. It may be speculated whether such differences in stress responses may contribute to lower cardiovascular risk in premenopausal women than in men. PMID- 11771822 TI - Gender differences in the electrophysiological characteristics of atrioventricular conduction system and their clinical implications. AB - OBJECTIVE: The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. DESIGN: The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. RESULTS: The AH (83 +/- 15 ms) and His ventricular intervals in men (42 +/- 6 ms) were significantly longer than in women (78 +/- 14, 38 +/- 6 ms, p < 0.05, respectively), as was the PR interval (160 +/- 17 vs 152 +/- 13 ms, p = 0.02). The effective refractory period of AV node in men (349 +/- 75 ms) was longer than in women (297 +/- 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 +/- 76 ms) than in women (330 +/- 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 +/- 107 vs 384 +/- 90 ms. p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). CONCLUSION: The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation. PMID- 11771823 TI - Comparison between circumflex artery motion and mitral annulus motion. AB - OBJECTIVE: To compare mitral annulus motion (MAM) with circumflex artery motion (CXM) and the motion amplitude at an endocardial site (representing MAM) with an epicardial site (representing CXM) at the most basal lateral part of the atrioventricular plane (AVP). DESIGN: MAM and CXM were obtained in 28 patients examined by echocardiography and coronary angiography. The motion amplitude epicardially and endocardially was recorded by echocardiography in 13 patients with normal ejection fraction (EF) (> or = 0.50) and in 13 patients with decreased EF (<0.50). RESULTS: CXM was higher than MAM in most patients with normal EF but lower than MAM in most patients with decreased EF. The motion amplitude epicardially was significantly higher (p < 0.001) than endocardially in patients with normal EF. while there was no significant difference in patients with decreased EF. CONCLUSION: CXM represents the motion of the epicardial part of the AVP and differs from MAM, which represents the endocardial part of the wall. This must be considered when CXM is used for assessment of left ventricular systolic function. PMID- 11771824 TI - Color encoding of the two-dimensional echocardiograms to analyze the echo texture of thickened mitral leaflets. AB - OBJECTIVE: The visual identification of different brightness of two-dimensional echocardiograms has natural limitations. The aim of this study was to perform a color-encoding technique on the echocardiograms and to evaluate whether the thickened mitral valve due to different etiologies may exhibit different colors and textures. DESIGN: Two-dimensional echocardiograms in parasternal long axis view in late diastole were digitized in 28 patients with thickened mitral valves and 14 age-matched control subjects. These 28 patients included 14 patients with mitral valve prolapse (MVP) and 14 patients with rheumatic change of mitral valve (RMV). The mean gray level of the anterior mitral valve and the skewness of the histogram of gray level distribution of the anterior mitral valve were studied in all cases. RESULTS: A significantly greater mean gray level of mitral valves in patients with RMV (114 +/- 20, p < 0.001) and lesser mean gray level in patients with MVP (49 +/- 12, p = 0.041) compared to that of control subjects (62 +/- 18) were noted. The mitral valves of the echocardiograms of patients with MVP tended to show a blue-to-green color, while those of RMV tended to show a yellow-to orange color by this image processing system. Significant differences in skewness of the gray level distribution of mitral valves in control vs RMV (p = 0.001), control vs MVP (p = 0.005), and RMV vs MVP (p < 0.001) were also found. CONCLUSION: This study demonstrates that the thickened mitral valves due to MVP and RMV may exhibit different colors and textures. Digital image processing can provide additional information to conventional echocardiograms in characterizing different echo textures of the heart valves. PMID- 11771825 TI - Daytime ambulatory blood pressure correlates strongly with the echocardiographic diameter of aortic coarctation. AB - OBJECTIVE: To relate the echocardiographic aortic arch-diameter to ambulatory and clinic blood pressure (BP) in patients with aortic coarctation. DESIGN: Eighteen adult patients (50% men) were recruited from the coarctation registry of the Linkoping Heart Centre. Biplane-trans-oesophageal echocardiography (TEE) was performed with Acuson XP 128/10, ambulatory BP was recorded with Spacelab models 90202/90205. RESULTS: Systolic clinic and ambulatory BP levels were higher in patients than in the 36 controls (clinic BP: 146 +/- 25 mmHg vs 119 +/- 10 mmHg, p = 0.0009, ambulatory BP: 140 +/- 18 mmHg vs 124 +/- 11 mmHg, p = 0.009). The differences in diastolic BP levels were less obvious (clinic BP: 87 +/- 16 mmHg vs 76 +/- 8 mmHg, p = 0.02, ambulatory BP: 84 +/- 13 mmHg vs 77 +/- 9 mmHg, p = 0.052). Daytime ambulatory BP was more strongly related than clinic BP to the coarctation diameter (AD) (systolic BP r= -0.73, p = 0.0006 and r = -0.61, p = 0.007, respectively). In surgically corrected patients (n = 14) only the correlations between ambulatory systolic daytime (r = -0.61, p = 0.02) and night time (r = -0.58, p = 0.03) BP to AD was statistically significant. CONCLUSION: Ambulatory BP correlates strongly with aortic coarctation measured by TEE and would thus be the preferred technique for evaluating BP in this patient category. PMID- 11771826 TI - Effects of MgSO4 and glucose, insulin and potassium (GIK) on atrial conduction during the first 12 hours after DC-conversion of chronic atrial fibrillation. AB - OBJECTIVE: To investigate changes in atrial conduction induced by MgSO4 and glucose, insulin and potassium (GIK) during the first 12-h period of sinus rhythm after successful DC-conversion of chronic atrial fibrillation (CAF). METHODS: Signal-averaged P-wave duration, QRS-duration and PQ-time were recorded in 20 patients who were randomly assigned to control or intervention. Ten patients received no infusates (control group) and 10 patients received MgSO4 and GIK infusions (intervention group). P-wave duration was determined from the X-, Y- and Z-leads, which were further combined to obtain a spatial magnitude. P-wave morphology was studied by analysing global activation patterns and discrete components from the calculated spatial magnitude signal. RESULTS: No changes in the measured parameters were seen in the control group. The P-wave duration, QRS duration and PQ-time increased from 139(13) [mean(SD)] to 149(15) (p < 0.01), 90(7) to 94(9) (p < 0.05) and 188(10) to 207(13) ms (p < 0.01). respectively, after bolus infusion of MgSO4. The time from the start of the P-wave to its 1st and 2nd max. locations increased by 6 ms (p < 0.01) in both cases after bolus infusion of MgSO4 and had reversed after 10 h of MgSO4 and GIK infusion. P-wave duration and PQ-time decreased after 10 h of MgSO4 and GIK infusion, from 149(34) (bolus) to 138(12) and from 207(13) to 195(27) ms (p < 0.05), respectively, in spite of an even higher serum Mg concentration at the end of this period. CONCLUSION: Bolus infusion of MgSO4 2 h after DC-conversion of CAF produced an intra-atrial conduction delay that could be reversed by adding a GIK infusion, in spite of a concomitant increase in serum Mg concentration. No recovery of the intra-atrial conduction delay, seen after DC-conversion of CAF, was observed in either of the two groups during the 12-h study period. PMID- 11771828 TI - Determination of traces of five antifouling agents in water by gas chromatography with positive/negative chemical ionisation and tandem mass spectrometric detection. AB - A highly selective and sensitive gas chromatography-mass spectrometry methodology has been developed for the determination of five antifouling compounds, currently licensed for use in marine antifouling paints. The procedure uses an ion trap mass spectrometer provided with an external ion source that allows the combined use, in the same analysis, of positive (PCI) and negative (NCI) chemical ionisation and tandem mass spectrometric fragmentation (MS-MS). Ionisation and fragmentation processes were optimised individually for each compound, thus, permitting maximum sensitivity and selectivity to be obtained. A complete validation study, including those aspects that affect both correct quantification and unequivocal confirmation, demonstrated the good performance of the proposed method. Detection limits obtained were lower than 0.005 microg l(-1), except for Irgarol 1051 (0.050 microg l(-1)). The method was applied to real seawater samples from different PMID- 11771827 TI - Insulin (GIK) improves central mixed and hepatic venous oxygenation in clinical cardiac surgery. AB - OBJECTIVE: Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? DESIGN: Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35 degrees C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. RESULTS: GIK was associated with reduced systemic vascular resistance (p = 0.02 vs the control group), higher bypass pump flow (p = 0.001). higher central mixed oxygen saturation (p = 0.036) and oxygen tension (p = 0.001) and higher hepatic venous oxygen saturation (p = 0.04) and oxygen tension (p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. CONCLUSION: 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6. PMID- 11771829 TI - Solid-phase microextraction versus single-drop microextraction for the analysis of nitroaromatic explosives in water samples. AB - This paper compares solid-phase microextraction (SPME) with a recently developed extraction method called single-drop microextraction (SDME) for the analysis of nitroaromatic explosives in water samples. The two techniques are examined in terms of procedure, chromatographic analysis and method performance. All practical considerations for both techniques are also reviewed. SPME requires dedicated apparatus and is relatively expensive, as the fiber's lifetime is limited. However, it has the advantages over SDME that it can be easily used for headspace analysis and has lower detection limits for all the target analytes. SDME requires more elaborate manual operations, thus affecting linearity and precision. PMID- 11771830 TI - Synthesis and evaluation of molecularly imprinted polymers for extracting hydrolysis products of organophosphate flame retardants. AB - A molecularly imprinted polymer (MIP) that selectively retains diphenyl phosphate was prepared using a structural analogue, ditolyl phosphate, as a template. Diphenyl phosphate is a degradation product of the flame retardant additive, triphenyl phosphate. The latter has been shown to be a common airborne contaminant in indoor environments and to be emitted from various goods such as video display units. Triphenyl phosphate induces several documented biological responses, including allergenic effects. Two different polymers, one prepared from methacrylic acid and the other from 2-vinylpyridine (2-Vpy), were investigated for their ability to recognise diphenyl phosphate. The polymers were used in solid-phase extraction cartridges (MISPE) and evaluated by comparing their recovery and breakthrough parameters with those of corresponding non imprinted polymers (NIPs). The polymer made from the basic monomer showed the most selective recognition to the acidic analyte. Diphenyl phosphate was adsorbed to the basic MIP (2-Vpy-MIP) when methanol was used as mobile phase, and approximately 80% of the analyte was recovered when eluted from this polymer using a mixture of methanol and trifluoroacetic acid. There was a clear difference in the retention strengths of 2-Vpy-MIP and the corresponding 2-Vpy NIP. The selectivity of the investigated 2-Vpy-MIP polymer towards a structural analogue of diphenyl phosphate, di(2-ethylhexyl) phosphate was also assessed. This compound was less strongly retained using the same experimental conditions. The results indicate that the prepared 2Vpy-MIP strongly recognises diphenyl phosphate due to the imprinting effect. This interaction probably arises mostly from an ionic interaction between the basic monomers and the acidic analyte. An LC-electrospray ionisation multiple MS method, using negative ion detection and ion-pair chromatography, was developed for separation and quantification of the strongly acidic dialkylated phosphate esters. The instrumental limit of detection was below 50 pg for all investigated compounds and the MS method was shown to be linear in the investigated range of 0.05-85 ng. PMID- 11771831 TI - Preparation of sterol-imprinted polymers with the use of 2-(methacryloyloxy)ethyl phosphate. AB - Steroid-selective polymers were prepared by the molecular imprinting technique, using 2-(methacryloyloxy)ethyl phosphate as functional monomer. The retentivity and selectivity of the obtained imprinted polymers were evaluated by liquid chromatography. The cholesterol-imprinted polymer showed higher affinity for cholesterol than that for cholesterol derivatives. The selectivity of the imprinted polymer was superior to the imprinted polymer prepared with the conventional functional monomer, 2-(trifluoromethyl)acrylic acid. Estradiol was also imprinted and gave similar results, demonstrating that 2 (methacryloyloxy)ethyl phosphate would be suitable for imprinted polymers of cholesterol and related compounds. PMID- 11771832 TI - Simultaneous determination of delta-aminolevulinic acid, porphobilinogen, levulinic acid and glycine in culture broth by capillary electrophoresis. AB - Capillary electrophoretic simultaneous determination of a mixture containing delta-aminolevulinic acid, porphobilinogen, levulinic acid and glycine was investigated. With increases in the sodium tetraborate buffer concentration (5-70 mM), resolution of the four components was improved, but the migration time was increased. Alternatively, with increases in the applied voltage (5-22.5 kV), a shortened migration time was seen but this adversely affected resolution. The components were separated with high resolution by using a fused-silica capillary column (75 cm x 75 microm I.D.) filled with 30 mM sodium tetraborate buffer (pH 9.3-9.4) under the applied voltage of 20 kV (constant voltage mode). When the established method was applied to the culture broth of Rhodopseudomonas sphaeroides, a photosynthetic bacterium, the four components mentioned above were separated with good resolution. Furthermore, the use of this method would provide a fast, sensitive and specific method for monitoring the administration of delta aminolevulinic acid in photodynamic cancer therapy, for the measurement of delta aminolevulinic acid dehydratase activity in erythrocytes, and for testing the delta-aminolevulinic acid assay and for impurities in drug formulation. PMID- 11771833 TI - Use of solid-phase extraction in various of its modalities for sample preparation in the determination of estrogens and progestogens in sediment and water. AB - The environmental analysis of estrogens and progestogens at physiologically active concentrations (low ng/l range) requires the use of very sensitive and selective methods, which, in most cases, make necessary an extraction/purification step. In this study, various procedures for the determination of several estrogens (estriol, estradiol, ethynyl estradiol, estrone, and diethylstilbestrol) and progestogens (progesterone, norethindrone, and levonorgestrel) in environmental matrices, including water and river sediment, are described. In all procedures, final analysis of the target compounds is performed by reversed-phase liquid chromatography-diode array detection-mass spectrometry, whereas sample preparation always includes a solid phase extraction (SPE) step. For this SPE step. various types of sorbents, protocols, and devices have been used, and their respective advantages and disadvantages are discussed. For the off-line SPE of estrogens and progestogens from water samples, a syringe type cartridge LiChrolut RP-18 (500 mg) was selected out of two other sorbents--LiChrolut EN (200 mg) and Isolut ENV (500 mg) -for use with the automated sample preparation instrument ASPEC XL. For the on line SPE and analysis of water samples the 10 mm x 2 mm I.D. HySphere-Resin-GP cartridge, was preferred to the C18 Baker, the PLRP-S, and the Oasis HLB. for use with the Prospekt system. A completely manual protocol based on the use of Sep Pak C18 Plus cartridges was developed for purification of sediment extracts. All procedures were shown to be linear over a wide range of concentration, exhibited satisfactory repeatability and accuracy, and reached limits of detection usually in the low ng/l and ng/g range. Comparatively, the on-line method was shown to be advantageous in terms of automation and general method performance. PMID- 11771834 TI - Determination of the herbicide amitrole in water with pre-column derivatization, liquid chromatography and tandem mass spectrometry. AB - Amitrole is a widely used polar herbicide, difficult to isolate from water. Due to its persistence, it can easily pollute ground and surface waters used in drinking water production. A fully automated on-line SPE-HPLC (solid-phase extraction-high-performance liquid chromatography) method with atmospheric pressure chemical ionisation-tandem mass spectrometry detection is described for the determination of amitrole. A pre-column derivatization with 9 fluorenylmethoxycarbonyl chloride directly in the native aqueous sample allows an enrichment step by SPE and HPLC separation. Due to the sensitivity of tandem mass spectrometric detection, a limit of detection and quantification as low as 0.025 microg/l was achieved in drinking water and ground and surface water. Based on the constant ratio of two selected product ions together with the retention time, the identification is very selective and quantitation is very reliable. The performance characteristics of the described method fully meet the requirements set by the EU Drinking Water Directive: recoveries of >95% in drinking water and >75% in surface water were achieved, as well as RSD values for repeatability of <9% in drinking water and <12% in surface water (determined at a spiking level of 0.1 microg/l). The method was successfully applied to real samples of ground and surface water with actual concentration up to 1.1 microg/l. PMID- 11771835 TI - Clean-up procedures for the analysis of heterocyclic aromatic amines (aminoazaarenes) from heat-treated meat samples. AB - The purpose of the study was to determine optimum conditions for the isolation and quantitation of five most biologically active aminoazaarenes [2-amino-3 methylimidazo[4,5-f]quinoline (IQ), 2-amino3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8 trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP)]. Some multistep procedures based on ultrasonic extraction, Soxhlet extraction, liquid-liquid extraction and solid phase extraction (SPE) were tested in order to choose the optimum isolation conditions for aminoazaarenes from fried meat samples spiked with known amounts of standards. According to the tested methods the qualitative-quantitative analysis was performed on the unspiked sample of pork roasted in typical household conditions. The qualitative-quantitative analysis of the aminoazaarenes was performed by a HPLC method. A HPLC Hewlett-Packard HP 1090 liquid chromatograph equipped with a UV diode array detector (DAD) was used. Chemically bonded HPLC columns C8 and TSK-gel ODS 80-T(M) were used under gradient elution conditions. A two-component mixture containing triethylamine-phosphate buffer (pH 3.2 and 3.3) and acetonitrile was used as a mobile phase. The results of the studies showed that a solid-phase extraction procedure using diatomaceous earth (Extrelut, 20 ml), propylsulphonic acid (PRS, 500 mg) and octadecylsilane (C18, 500 mg) columns was the quickest and simplest one. Recoveries of the aminoazaarenes, spiked and isolated from meat samples by the chosen SPE procedure, were as follows: IQ 85%, MeIQ 50%, MeIQx 46%, 4,8-DiMeIQx 62%, PhIP 50%. PMID- 11771836 TI - Determination of domoic acid in shellfish by liquid chromatography with electrospray ionization and multiple tandem mass spectrometry. AB - Amnesic shellfish poisoning is a potentially lethal human toxic syndrome which is caused by domoic acid (DA) that originates in marine phytoplankton belonging to the Pseudonitzschia genus. A new sensitive liquid chromatographic-mass spectrometry (LC-MS) method has been developed for the determination of DA in various marine biological samples. The characteristic fragmentation pathways for DA were established using multiple stage MS on selected daughter ions, which were sequentially trapped and fragmented. Chromatography was performed using a gradient of acetonitrile-water (5:95 to 40:60), containing trifluoroacetic acid (0.05%), over 25 min at 0.2 ml/min with a C18 column (Luna-2, 150 x 2.0 mm, 5 microm). Using electrospray ionisation, multiple tandem MS experiments were performed with an ion-trap mass spectrometer (Finnigan MAT LCQ). The protonated DA molecule was the precursor ion, m/z 312, and the relative collision energies were optimised for multiple MS (MS(n), n = 2-4) studies. LC-MS3 using the ions, m/z 266 and 220, from the loss of two HCOOH molecules, produced the best sensitivity data. Calibration data for various MS modes were: MS (0.05-10 microg DA/ml, r2 = 0.9973); MS2 (0.025-10 microg DA/ml, r2=0.9997); MS3 (0.025-10 microg DA/ml, 0.9994). The detection limits (3:1 signal:noise) were better than 0.02 microg DA/ml for LC-MS, 0.014 microg DA/ml for LC-MS2 and 0.008 microg DA/ml for LC-MS3. This method was applied to determine DA in scallop (Pecten maximus) tissues, which subsequently led to the closure of several shellfish harvesting sites on the west coast of Ireland. PMID- 11771837 TI - Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry. AB - An analytical method is presented enabling the determination of nine neutral pharmaceuticals in groundwater, and for most of the compounds, in rivers and wastewater down to the lower ng/l range. The analytes belong to different medicinal groups such as antiphlogistics, psychiatric drugs and antidiabetics. Samples are enriched using solid-phase extraction (SPE) with RP-C18ec material. Analysis is performed by liquid chromatography with detection by electrospray tandem MS. Mean recoveries generally exceed 80% in groundwater, and the quantification limits are down to 50 ng/l in wastewater and down to 10 ng/l in groundwater. Losses were observed to occur either from ion suppression in the electrospray ionisation or SPE. Losses for all compounds could not be compensated for by the surrogate standard dihydrocarbamazepine. In raw municipal wastewater, concentration levels were detected for caffeine up to 147 microg/l and for propyphenazone up to 1.3 microg/l. PMID- 11771838 TI - Determination of drugs in surface water and wastewater samples by liquid chromatography-mass spectrometry: methods and preliminary results including toxicity studies with Vibrio fischeri. AB - In the present work a combined analytical method involving toxicity and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was developed for the determination of pharmaceutical compounds in water samples. The drugs investigated were the analgesics: ibuprofen, ketoprofen, naproxen, and diclofenac, the decomposition product of the acetyl salicylic acid: salicylic acid and one lipid lowering agent, gemfibrozil. The selected compounds are acidic substances, very polar and all of them are analgesic compounds that can be purchased without medical prescription. The developed protocol consisted, first of all, on the use Microtox and ToxAlert 100 toxicity tests with Vibriofischeri for the different pharmaceutical drugs. The 50% effective concentration (EC50) values and the toxicity units (TU) were determined for every compound using both systems. Sample enrichment of water samples was achieved by solid-phase extraction procedure (SPE), using the Merck LiChrolut EN cartridges followed by LC-ESI-MS. Average recoveries loading 11 of samples with pH=2 varied from 69 to 91% and the detection limits in the range of 15-56 ng/l. The developed method was applied to real samples from wastewater and surface-river waters of Catalonia (north-east of Spain). One batch of samples was analyzed in parallel also by High Resolution Gas Chromatography coupled with Mass Spectrometry (HRGC-MS) and the results have been compared with the LC-ESI-MS method developed in this work. PMID- 11771839 TI - Pharmaceuticals in groundwaters analytical methods and results of a monitoring program in Baden-Wurttemberg, Germany. AB - In this paper, analytical methods for the trace-level determination of 60 pharmaceuticals in aqueous samples are presented. The list of compounds amenable to the methods comprises analgesics, antiphlogistics, antirheumatics, beta blockers, broncholytics, lipid-lowering agents (or their metabolites), antiepileptics, vasodilators, tranquillizers, antineoplastic drugs, iodinated X ray contrast media, and antibiotics of different kind, mainly sulfonamides, macrolides, and penicillins. All methods are based on automated solid-phase extraction followed by GC-MS (after derivatization of the acid compounds) or HPLC electrospray ionization MS-MS. After an intense validation, which included the determination of performance data according to the German standard method DIN 32645 (limit of detection, limit of identification, limit of determination), the determination of linearity, recovery, and repeatability and the study of matrix effects, the analytical methods were applied within a monitoring program on the occurrence of pharmaceuticals in groundwaters of Baden-Wurttemberg. During this monitoring program, it was found that several of the compounds under investigation could be detected in groundwaters and their occurrence could be traced back to an impact of municipal or industrial waste water. PMID- 11771840 TI - Sample treatment in chromatography-based speciation of organometallic pollutants. AB - Speciation analysis is nowadays performed routinely in many laboratories to control the quality of the environment, food and health. Chemical speciation analyses generally include the study of different oxidation state of elements or individual organometallic compounds. The determination of the different chemical forms of elements is still an analytical challenge, since they are often unstable and concentrations in different matrices of interest are in the microg l(-1) or even in the ng l(-1) range (e.g., estuarine waters) or ng g(-1) in sediments and biological tissues. For this reason, sensitive and selective analytical atomic techniques are being used as available detectors for speciation, generally coupled with chromatography for the time-resolved introduction of analytes into the atomic spectrometer. The complexity of these instrumental couplings has a straightforward consequence on the duration of the analysis, but sample preparation to separate and transfer the chemical species present in the sample into a solution to be accepted readily by a chromatographic column is the more critical step of total analysis, and demands considerable operator skills and time cost. Traditionally, liquid-liquid extraction has been employed for sample treatment with serious disadvantages, such as consumption, disposal and long-term exposure to organic solvent. In addition, they are usually cumbersome and time consuming. Therefore, the introduction of new reagents such as sodium tetraethylborate for the simultaneous derivatization of several elements has been proposed. Other possibilities are based in the implementation of techniques for efficient and accelerated isolation of species from the sample matrix. This is the case for microwave-assisted extraction, solid-phase extraction and microextraction, supercritical fluid extraction or pressurized liquid extraction, which offer new possibilities in species treatment, and the advantages of a drastic reduction of the extraction time and the embodiment into on-line flow analysis systems. This new generation of treatment techniques constitutes a good choice as fast extraction methods for feasible species-selective analysis of organometallic compounds under the picogram level, that can be used for national regulatory agencies, governmental and industrial quality control laboratories, and consequently, for manufacturers of analytical instrumentation. PMID- 11771841 TI - Derivatization of organometal(loid) species by sodium borohydride problems and solutions. AB - Like other derivatization techniques, hydride generation is a chemical reaction that produces side-reactions leading to analytical problems. Demethylation of dimethylarsinic acid was observed to be dependent upon the pH level of the hydride generation reaction mixture. If the reaction mixture was acidic, then in addition to (CH3)2AsH, the monomethyl arsenic hydride [(CH3)AsH2] could be detected. Demethylation and also the formation of an unidentified arsenic species were noted when trimethyl arsonic oxide was used as derivatization educt. All of these effects depend on the pH level of the hydride generation mixture. We observed significant levels of organometal(loid) species of elements such as Ge, As, Sn, Sb, Hg and Bi in blank hydride generation mixtures. The organometal(loid) contamination was irreproducible even during I day using a single solution of sodium borohydride in deionized water. We concluded that the organometal(loid) contamination arises directly from the derivatization agent, sodium borohydride, itself. Use of helium purging and various adsorptive materials to decontaminate the sodium borohydride solution prior to analysis did not result in a significant decrease in organometal(loid) contamination levels. Use of a palladium-cluster stabilised with 1,10-phenanthrolin as alternative hydride generation derivatization agent was not found to be suitable, since reaction yields were poor and transmethylation reactions were noted. PMID- 11771842 TI - Microwave assisted solvent extraction and coupled-column reversed-phase liquid chromatography with UV detection use of an analytical restricted-access-medium column for the efficient multi-residue analysis of acidic pesticides in soils. AB - A screening method has been developed for the determination of acidic pesticides in various types of soils. Methodology is based on the use of microwave assisted solvent extraction (MASE) for fast and efficient extraction of the analytes from the soils and coupled-column reversed-phase liquid chromatography (LC-LC) with UV detection at 228 nm for the instrumental analysis of uncleaned extracts. Four types of soils, including sand, clay and peat, with a range in organic matter content of 0.3-13% and ten acidic pesticides of different chemical families (bentazone, bromoxynil, metsulfuron-methyl, 2,4-D, MCPA, MCPP, 2,4-DP, 2,4,5-T, 2,4-DB and MCPB) were selected as matrices and analytes, respectively. The method developed included the selection of suitable MASE and LC-LC conditions. The latter consisted of the selection of a 5-microm GFF-II internal surface reversed phase (ISRP, Pinkerton) analytical column (50 x 4.6 mm, I.D.) as the first column in the RAM-C18 configuration in combination with an optimised linear gradient elution including on-line cleanup of sample extracts and reconditioning of the columns. The method was validated with the analysis of freshly spiked samples and samples with aged residues (120 days). The four types of soils were spiked with the ten acidic pesticides at levels between 20 and 200 microg/kg. Weighted regression of the recovery data showed for most analyte-matrix combinations, including freshly spiked samples and aged residues, that the method provides overall recoveries between 60 and 90% with relative standard deviations of the intra-laboratory reproducibility's between 5 and 25%; LODs were obtained between 5 and 50 microg/kg. Evaluation of the data set with principal component analysis revealed that the parameters (i) increase of organic matter content of the soil samples and (ii) aged residues negatively effect the recovery of the analytes. PMID- 11771843 TI - Removal of metal ions from aqueous solution by adsorption on the natural adsorbent CACMM2. AB - The adsorption of Cd2+, Cr3+, Cu2+, Fe3+, Ni2+, Pb2+ and Zn2+ from aqueous solution was used to study the sorption properties of the adsorbent CACMM2 extracted from a cactus. Quantitation of the cation concentrations was performed by HPLC with diode array detection using on-column complex formation with 8 hydroxyquinoline. Removal degree from 100 mg M(n+) l(-1) solutions followed the series: Cu>Cd>Fe>Ni>Cr>Zn. Henry and Freundlich constants were determined since adsorption did not reach saturation plateaux in the studied concentration interval. Sorption of chromium by CACMM2 was stronger than the sorption onto lignin, calcium oxalate and cellulose up to 1,000 mg Cr3+ l(-1). Copper and iron were desorbed to a greater extent, while lead adsorption was practically irreversible. CACMM2 was able to remove more than 83% of chromate in a freshly prepared and exhausted chromate commercial solution. PMID- 11771844 TI - Monitoring of pesticides in drinking and related waters in NE Spain with a multiresidue SPE-GC-MS method including an estimation of the uncertainty of the analytical results. AB - A new method, developed in an EC project (SMT4-CT96-2142) for the determination of 22 pesticides in drinking and related waters, has been used to analyze source and drinking water samples in the area of Barcelona (NE Spain). The procedure includes solid-phase extraction of water and subsequent analysis by GC-MS using few selected ions (SIR) in order to increase their sensitivity. The method was subjected to intra and interlaboratory tests and met the requirements of the EC Directive in terms of accuracy, precision and detection limit (0.025 microg/l range in water samples). A detailed analysis of the uncertainty sources of this method is included, which allows to estimate expanded uncertainties in the 10-20% range. The dominant sources of uncertainty are the solid-phase extraction procedure and the chromatographic quantification. Two triazine compounds, simazine and atrazine, are the main pesticides detected in wells of the Llobregat river and in water of the Ter river, respectively. PMID- 11771845 TI - Molecularly imprinted solid-phase extraction sorbent for the clean-up of chlorinated phenoxyacids from aqueous samples. AB - A molecularly imprinted polymer (MIP) was synthesized using the herbicide 2,4,5 trichlorophenoxyacetic acid as a template, 4-vinylpyridine as an interacting monomer, ethylendimethacrylate as a cross-linker and a methanol-water mixture as a porogen. The binding properties and the selectivity of the polymer towards the template were investigated by frontal and zonal liquid chromatography. The polymer was used as a solid-phase extraction material for the clean-up of the template molecule and some related herbicides (2,4-dichlorophenoxyacetic acid, fenoprop, dichlorprop) from river water samples at a concentration level of ng/ml with quantitative recoveries comparable with those obtained with a traditional C18 reversed-phase column when analyzed by capillary electrophoresis. The results obtained show that the MIP-based approach to the solid-phase extraction is comparable with the more traditional solid-phase extraction with C18 reversed phase columns in terms of recovery, but it is superior in terms of sample clean up. PMID- 11771846 TI - Determination of haloacetic acids in aqueous environments by solid-phase extraction followed by ion-pair liquid chromatography-electrospray ionization mass spectrometric detection. AB - Haloacetic acids (HAAs) were determined in different water samples by a new, fast and simple analysis method based on enrichment of 50-ml water samples at pH 1.8 by solid-phase extraction (SPE) followed by liquid chromatography (LC) separation and electrospray ionization mass spectrometric detection in the negative ionization mode. Deprotonated (M-H)-haloacetates and decarboxylated (M-COOH)- ions were detected. Different polymeric SPE sorbents were tested, and LiChrolut EN was found to be the best material for the extraction. Complete LC separation of all compounds could only be achieved by ion-pair chromatography using triethylamine as volatile ion-pairing reagent. The detection limits were in the low microg/l range. High microg/l concentration levels for the chlorinated and brominated haloacetates were found in drinking water from a drinking water treatment plant in Barcelona, and the corresponding tap water. In swimming pool water samples from Catalonia mg/l levels and in surface river water from Portugal microg/l values were detected. These results confirm other recent reports on the ubiquitous occurrence of HAAs in aqueous environments. PMID- 11771847 TI - Quantitative analysis of polycyclic aromatic hydrocarbons in sewage sludge from wastewater treatment plants. AB - Polycyclic aromatic hydrocarbons (PAHs) are an important group of organic contaminants present in sewage sludge. Due to their persistence and toxic potential, information about their presence in sewage sludge is needed in order to assess applicability on agricultural land. A method for the gas chromatographic-mass spectrometric (GC-MS) determination was developed and applied to the trace determination of PAHs present in sewage sludge samples from six wastewater treatment plants (WWTPs) differing in the type of treatment and the origin of wastewater. PAHs were extracted from freeze-dried samples by a dichloromethane-methanol (2:1) mixture in a sonication bath. The sludge extracts were cleaned-up by an alumina column. The method showed recovery values varying from 60 to 98%. Four surrogate standards ([2H8]naphthalene, [2H10]anthracene, [2H12]benzo[a]anthracene, and [2H12]benzo[ghi]perylene) were used for quantitation by GC-MS. A reference sludge sample was analysed in order to validate the method. The sum of the 16 US Environmental Protection Agency PAHs analysed in the sewage sludge samples varied from 1.13 to 5.52 mg/kg. No significant difference between the different WWTPs was found. PMID- 11771848 TI - Recalcitrance of poly(vinylpyrrolidone): evidence through matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. AB - The aerobic biodegradability of an extensively used synthetic polymer was monitored the first time on a laboratory-scale fixed-bed bioreactor (FBBR) applying matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Polymeric poly(vinylpyrrolidone) (PVP) was spiked at concentrations of 10 mg l(-1) onto the FBBR run with river water and the biodegradation monitored after lyophilization of aliquots of the test liquor applying MALDI-TOF-MS. The latter proved to be a powerful tool for qualitative screening purposes of PVP in a molecular mass range <20 kDa in particularly yielding a high sensitivity and shot-to-shot reproducibility. The sample-to sample reproducibility was enhanced applying the anchor target device. Post source decay-MALDI-TOF-MS fragmentation investigations determined the unknown end groups of PVP unambiguously. Poor biodegradability of PVP can be assumed, since even after 30 days, no oxidation of the terminal groups and no difference in the repeating units was observed. A decrease in the molecular mass distribution can be drawn back rather to adsorption of PVP in the FBBR other than to biodegradation. This was further investigated performing an adsorption experiment with sewage sludge as solid matrix and analyses of the aqueous phase and sludge samples. Extrapolating these results to the situation in wastewater treatment plants, it is highly likely that PVP is eliminated from the dissolved phase by adsorption onto sludge particles. PMID- 11771849 TI - Analysis of nonylphenol and nonylphenol ethoxylates in environmental samples by mixed-mode high-performance liquid chromatography-electrospray mass spectrometry. AB - A new method is described based on mixed-mode high-performance liquid chromatography with electrospray mass spectrometry detection for comprehensive quantitative analysis of nonylphenol (NP) and nonylphenol ethoxylates (NPEOs) in wastewater and sediment. Efficient separation, reduced band broadening, and high sensitivity were achieved by employing a methanol-water gradient on a mixed solvent gel filtration column designed for MS interfacing. Quantitative accuracy and precision of the method were improved by the use of custom-synthesized [13C6]NPEO analogs as isotope-dilution surrogate standards. Method detection limits for NP and individual NPEOs ranged from I to 55 pg injected on column. PMID- 11771850 TI - Solid-phase microextraction of phthalates from water. AB - Solid-phase microextraction (SPME) with six different non-polar and polar fibres was used to extract seven phthalate esters from water samples for analysis by gas chromatography-mass spectrometry. With regard to extraction efficiency and repeatability of the extractions, the 70-microm Carbowax-divinylbenzene fibre was especially suitable for the selected phthalates with water solubilities between 4200 mg l(-1) (dimethyl phthalate) and 0.0003 mg l(-1) (di-n-octyl phthalate). Linearity was controlled in the range between 0.02 and 10 microg l(-1). In analysed drinking water samples from Leipzig (Germany) and Katowice (Poland) four of the investigated phthalates [diethyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate] were found to be present in concentrations between 0.02 and 0.6 microg 1(-1). PMID- 11771851 TI - In vitro assay of collagen gel contraction by cardiac fibroblasts in serum-free conditions. AB - The aim of the present study was to investigate whether collagen gel contraction can be induced by cardiac fibroblasts in serum-free conditions. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and added to a hydrated collagen gel in Dulbecco's Modified Eagle's Medium with or without fetal bovine serum for 1, 2, 3 or 7 days. Control gels containing adult rat cardiac fibroblasts showed a significant amount of contraction after 2 days of incubation in a serum-free medium, causing a contraction to 47% of the area at the start of the incubation. Increasing the percent of fetal bovine serum induced further stimulation of the collagen gel contraction by cardiac fibroblasts. Optimal conditions for collagen gel contraction by adult fibroblasts were obtained with 100,000 cells incubated for 1 (up to 3) days. The presence of insulin-transferrin-selenium in the medium caused a more pronounced stimulation of the collagen gel contraction by cardiac fibroblasts, while sodium azide inhibited this contraction. PMID- 11771853 TI - Lipophilic statins can be osteogenic by promoting osteoblastic calcification in a Cbfa1- and BMP-2-independent manner. AB - Mevastatin (3-10 microM) and fluvastatin (0.1-10 microM), but not pravastatin, were found to promote calcification of MC3T3-E1 cells and their subclone MC4, in either the presence or absence of 3 mM inorganic phosphate stimulus. The mechanism of action was examined. Gel retardation assay and immunocytochemical analysis of core binding factor (Cbfa1) revealed that mevastatin and fluvastatin completed the nuclear export of Cbfa1, possibly thereby reducing the induction of the stably transfected p6OSE2-luc gene, and then promoted Cbfa1-independent calcification, which invariably occurred in both wild type and dominant negative Cbfa1-expressing cells. The induction of the bone morphogenetic protein-2 (BMP-2) gene promoter failed to respond to the statins. All the effects of the cell permeable statins were negated by mevalonate pathway metabolites (geranylgeranylpyrophosphate > farnesylpyrophosphate > mevalonate) and reproduced by toxin B (a Rho-specific inhibitor), but not totally by Y27632 (a ROCK-specific inhibitor). The results suggest that lipophilic statins can be osteogenic by promoting Cbfa1- and BMP-2-independent calcification processes. PMID- 11771852 TI - Effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils. AB - The effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils were studied. The histamine and H2 agonists impromidine and 4-methylhistamine caused concentration-related increases in the number of differentiated cells. On the other hand, the H1 agonists 2-methylhistamine and 2 pyndylethylamine showed no such effect. Histamine-induced eosinophil differentiation was antagonized by the H2 antagonists cimetidine and ranitidine. Histamine and H2 agonists inhibited (3H)-thymidine uptake, suggesting that these compounds caused a decrease in proliferation. Histamine as well as the H2 agonists impromidine and 4-methythistamine caused increases in cAMP level, and this effect was antagonized by ranitidine. From these findings, we concluded that both the differentiation of HL-60-Eo cells into eosinophils and proliferation of HL-60-Eo cells were mediated via H2 receptors. PMID- 11771854 TI - Bisphenol A enhances cadmium toxicity through estrogen receptor. AB - To clarify the action of estrogenic endocrine disruptors on cadmium (Cd)-induced metallothionein (MT) synthesis in the liver, we investigated the effects of bisphenol A (BPA) on hepatic MT-I mRNA expression and MT contents after Cd injection. Liver damage after Cd injection was assessed by measuring glutamic pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) activities in the serum. It was found that BPA reduced the Cd-induced expression of MT-I mRNA and MT protein in the liver. The administration of tamoxifen, an estrogen receptor antagonist, prevented the reduction of hepatic MT content by PA. Moreover both the GPT and GOT activities of the BPA-treated groups were higher than those of the control groups. These findings suggest that BPA reduced hepatic MT synthesis after Cd injection via the estrogen receptor which resulted in increased damage to the liver. PMID- 11771855 TI - Influence of acute copper deficiency, cold-restraint stress and the H2 blocker ranitidine on the severity of acute gastric mucosal lesions and lipid peroxidation in rats. AB - Acute copper deficiency produces disturbances in the microcirculation and structure of extracellular matrix proteins, causes an increase in mast cell population, which is followed by an increased content of their degranulation products, produces disturbances in histamine metabolism and decreases the activity of some antioxidant enzymes. These pathogenic mechanisms are similar to the processes underlying stress ulcer formation. The histamine H2-receptor antagonist ranitidine, a drug with the highest application for stress ulcer prophylaxis, has the ability to helate the copper ion and to influence its tissue distribution and the processes of generation and neutralization of reactive oxygen species (ROS). In order to determine the interrelation between the disturbances of copper homeostasis, stress ulcers and ranitidine, we investigated the impact of a short-term diet with powdered milk in combination with cold restraint stress with or without ranitidine on the severity of acute gastric mucosal lesions, copper content, lipid peroxidation and the activity of superoxide dismutase and catalase in the stomachs of rats. PMID- 11771856 TI - Impact of pharmacotherapy on lymphocyte volumes and activity of the Na+/H+ exchanger in patients with congestive heart failure. AB - Previous studies in patients with congestive heart failure (CHF) have revealed abnormalities of cellular volume that might have an impact on the dysregulation of peripheral vascular resistance. Human mononuclear leukocytes (HML) represent a model for the study of cellular volume regulation. We investigated the impact of enalapril and carvedilol on HML volume and on the activity of the Na+/H+ exchanger in 26 patients with CHF and 20 volunteers. Over a period of 4 weeks, 18 patients received enalapril in addition to the previous therapy while 8 patients additionally received carvedilol. HML diameters and the activity of the Na+/H+ exchanger were measured by a Coulter Counter. Both patient groups showed abnormally increased initial volumes of HML compared to the volunteer group at baseline. Four weeks of therapy with enalapril in addition to therapy with diuretics and digoxin did not result in a statistically significant reduction of lymphocyte volume, whereas add-on therapy with carvedilol to therapy with ACE inhibitors, diuretics and digoxin reduced the volume significantly. Alterations could not be found in the activity of the Na+/H+ exchanger in either patient group compared to volunteers. Supplementary drug therapy with carvedilol in patients with CHF leads to a reduction of the increased lymphocytic volume, possibly reflecting the beneficial effect of beta-blockade. PMID- 11771857 TI - Acceptability and profile of the clinical drug trials underway in Finnish university hospitals in the 1990s: applications reviewed by ethics committees. AB - There is scarce information in literature about the decisions made by ethics committees concerning the clinical studies they have reviewed. A retrospective, detailed review of 666 applications, their amendments and the ethics committees' statements was undertaken. All protrocols of clinical studies on medicinal products submitted to and reviewed by the ethics committees of two university hospitals during the years 1992, 1994, 1996 and 1998 were investigated. Most of the studies were international (50%), multicenter (71%), phase III trials (41%) on a new clinical entity, (38%). Validity of the clinical drug study applications was acceptable in more than half of the cases (364; 55%), while 91 (14%) were approved with advisory comments, 153 (23%) had to be amended, 35 (5%) were left pending and 23 (3%) were rejected. Most of the questions pertained to informed consent and the study protcol. In accordance with precious results, our findings support the opinion that the submitted documents need to be improved, especially with regard to informed consent and study protocols, in order to gain better Good Clinical Practice (GCP) compliance. Well-defined, documented operating procedures of the ethics committees would have facilitated the practical issues in the review process. PMID- 11771858 TI - Chronic treatment with epidermal growth factor induces growth of the rat ventral prostate. AB - OBJECTIVE: The epidermal growth factor (EGF) system is expressed in the rat prostate, and growth factors from this system induce proliferation in prostate epithelial and stromal cell cultures. The aim of the study was to investigate the possible growth-promoting effects of the system during the hyperplastic growth phase of the prostate in newborn rats. MATERIAL AND METHODS: Newborn rats were treated for 8 weeks with EGF (150 microg/kg body weight per day), administered as daily subcutaneous injections. Sections of the prostate tissue were examined by a stereological technique to determine tissue composition. RESULTS: Treatment with EGF increased the weight of the ventral prostate, relative to body weight, by 50% compared with placebo (p < 0.005). Neither the dorsolateral prostate, seminal vesicles nor coagulating glands were affected by EGF. Prostate tissue showed a significant increase in the volume of the prostate epithelium, the stroma and the lumen following EGF treatment, in a pattern resembling physiological growth of the ventral prostate. A significant correlation (r = 0.78, p < 0.0001) of the volume fraction of the lumen with the glandular weight of the ventral prostate was seen. Serum testosterone was not affected by chronic EGF administration. CONCLUSIONS: EGF selectively induces growth of the ventral lobe of the prostate in newborn rats, in a pattern comparable to normal physiological growth. It may be hypothesized that the physiological growth of the prostate is directly correlated to endogenous activity of the EGF system in the rat prostate gland. PMID- 11771859 TI - Chemolysis of struvite stones by acidification of artificial urine--an in vitro study. AB - OBJECTIVE: The aim of the study was to look for strategies that improve the clinical outcome of struvite stones. An in vitro experimental set up with artificial stones made of struvite (BON(N)-STONES) was chosen to perform standardized and reproducible analyses on various artificial urines with pH values that may be reached by acidification with oral methionine treatment. MATERIALS AND METHODS: Artificial ball-shaped stones made of struvite (BON(N) STONES) with a diameter of 0.8 cm were used. The investigations on chemolysis were performed using a dissolution device which simulates the physiological conditions in the upper urinary tract with computer-assisted on line measurement of data. For chemolysis of struvite BON(N)-STONES artificial urines according to Griffith at four different pH-values (pH 5.75, pH 6.0, pH 6.25, pH 6.5) were used. Furthermore natural and struvite BON(N)-STONES were treated with Suby G solution (pH = 4.0). RESULTS: Comparing natural and artificial struvite stones after treatment with Suby G there was no significant difference regarding their dissolution rate. The dissolution rate of struvite stones in artificial urine rose with a decreasing pH-value. The diminution of the pH-value from 6.5 to 5.75 lead to an increase of the dissolution rate of more than 35%. This increase in the dissolution rate decreased with falling pH-value. CONCLUSIONS: The acidification of urine accelerated the dissolution rate of struvite stones in vitro. Considering in vivo conditions the intake of 1,500-3,000 mg L-methionine may lead to a sufficient acidification for a good dissolution of struvite stones. PMID- 11771860 TI - Evaluation of the autonomic nervous system function in children with primary monosymptomatic nocturnal enuresis--power spectrum analysis of heart rate variability using 24-hour Holter electrocardiograms. AB - OBJECTIVE: The purpose of this study was to evaluate the circadian rhythm of the autonomic nervous system functions of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: The subjects were allocated to three groups--enuresis group (n = 72), normal control group (n = 26), post-treated and cured enuresis group (n = 13). In the three groups. we evaluated the autonomic nervous system function by the power spectrum analysis of heart rate variability (HRV) using 24-hour Holter electrocardiograms. Frequency components of the power spectra of HRV (% power) were divided into three factors; the very low frequency (VLF), the low frequency (LF) and the high frequency (HF) by computer analysis using Fast Fourier Transformation (FFT). RESULTS: In the three groups, the HF component reflecting parasympathetic activity was significantly higher, compared with the LF during sleep. The HF in the enuresis group was significantly higher, compared with the HF in the control group during sleep. The HF in the control group was significantly lower, compared with the LF during waking. However, the HF in the enuresis group was significantly higher, compared with the LF during waking. It showed more increased parasympathetic tone in the enuresis group, compared with that of the control group during sleep and waking. In the post treated enuresis group, the HF during sleep and waking were significantly decreased, compared with those before treatment. CONCLUSION: These findings suggest the parasympathetic hyperfunction through 24 hours and abnormal circadian rhythm of autonomic nervous system functions in the enuresis group. The post treated enuresis group showed normal autonomic nervous system functions. PMID- 11771861 TI - Frequency of nightly wetting and the efficiency of alarm treatment of nocturnal enuresis. AB - OBJECTIVE: This study aimed to investigate the efficiency of alarm treatment in patients suffering from nocturnal enuresis (NE). MATERIAL AND METHODS: The weekly frequency of nightly wetting was used as an indicator of the patient's predisposition for alarm treatment and thus of the efficiency of the alarm. RESULTS: The pattern of relapse is shown in connection with a status I year after treatment ended for those who volunteered successful treatment. CONCLUSIONS: Patients with the highest pretreatment frequencies of NE achieved better results from treatment with an alarm and ended up in a better situation than those with lower frequencies of NE receiving the same treatment. PMID- 11771862 TI - Combination therapy for nocturnal enuresis. AB - Nocturnal enuresis (NE) is a multifactorial condition of childhood affecting both children and their parents. NE may result from a vasopressin deficiency, bladder instability or lack of arousal from sleep to bladder sensations. The development of the three-systems model offers increased understanding of the multifactorial aetiology of NE and may aid the development of a tailored treatment regimen for the individual child. For decades, treatment of NE has focused on pharmacological, behavioural and combination therapies, and many studies provide supporting evidence for each of these treatment approaches. However, many of these studies were performed on unselected patient populations. without assessment of the cause of the patients' enuresis, and therefore both the methodologies and results of these studies are questionable. This paper reviews the efficacy of combined treatment interventions and assesses when such interventions may be of most benefit to the patient. PMID- 11771863 TI - Results of a questionnaire evaluating different aspects of personal and familial situation, and the methods of potty-training in two groups of children with a different outcome of bladder control. AB - OBJECTIVE: This study aimed to investigate the family situation, personal behaviour and current micturition habits, the time of beginning and the method of potty-training in two groups of children with different outcomes of bladder control. MATERIAL AND METHODS: Parents of 140 children, between 7 and 15 years old, filled in a questionnaire comprising 43 questions. They were divided into a symptom group (n = 73) and a symptom-free group (n = 67) according to the outcome of bladder control. RESULTS: Parents remembered clearly the method of training and the time of starting the potty-training to achieve continence in their child, and the exact age at which these objectives were achieved. There was some confusion regarding the term incontinence: the majority of the parents (70%) considered their child to be continent in spite of day-wetting several times a week. All children with urge syndrome who had undergone a urodynamic investigation (n = 50) had an objective functional bladder disorder. CONCLUSIONS: Methods of training differed between the groups with and without lasting problems. The symptom group started training at a later age, had more tendency to punish and were more demanding when micturition did not start readily. The findings from the questionnaire strengthen the hypothesis that urge syndrome can be due to poor methods of potty-training. Very few parents searched spontaneously for help, which should prompt practitioners and paediatricians to be more alert to this problem. PMID- 11771864 TI - Association of non-urological diseases with lower urinary tract symptoms. AB - OBJECTIVE: Clinical observations indicate that many non-urological diseases seem to be associated with lower urinary tract symptoms (LUTS). This has also been shown in studies usually concerning single diseases. This study investigated the impact of non-urological diseases on LUTS in the general population. MATERIAL AND METHODS: A questionnaire on LUTS and medical history was mailed to all 50-, 60- and 70 year-old men in Tampere and in 11 municipalities in the same county, in total 3143 subjects. Day-time frequency, nocturia, urge, urge incontinence, hesitancy and incomplete emptying were used to form an index for LUTS. The men were asked to report any disease that they had. The number of the following diseases reported by the participants was large enough for statistical analysis: lower back pain, hypertension, arthritis, heart disease, pulmonary disease, diabetes, constipation. stroke, transient ischaemic attack, cancer (other than prostate or bladder), neurological disease, inguinal hernia, rheumatoid arthritis and faecal incontinence. The association between LUTS and non-urological diseases was estimated by logistic regression as a prevalence odds ratio (OR) with 95% confidence intervals (CI). RESULTS: In the multivariate analysis a significant association was found between LUTS and the following diseases: faecal incontinence (OR 4.5, CI 2 .3-9.1), neurological disease (OR 2.4, CI 1.3-4.4), constipation (OR 2.3, CI 1.5-3.3) and arthritis (OR 1.5, CI 1.2-2.0). CONCLUSIONS: According to this population-based study LUTS is an important part of the symptomatology of faecal incontinence, neurological disease, constipation and arthritis. Thus, the patients with these diseases and presenting with LUTS require careful investigation, at least in the cases in which the primary therapy of LUTS has failed. PMID- 11771865 TI - Vitamin B12 metabolism after urinary diversion with a Kock ileal reservoir. AB - OBJECTIVE: To elucidate the influence of construction of a Kock reservoir for urinary diversion using 70 cm of the distal ileum on vitamin B12 metabolism. MATERIAL AND METHODS: Blood samples for determination of cobalamin concentrations were drawn up to 18 years after construction of a Kock reservoir in 97 patients. Preoperative values were obtained in 20 of these patients. Pre- and postoperative Schilling tests and analyses of methylmalonic acid and homocysteine concentrations were performed in subgroups. RESULTS: The operation did not induce a significant decrease in cobalamin uptake as reflected in the pre- and postoperatively performed Schilling tests. No significant decline in cobalamin concentration postoperatively was noted. The value of analysis of methylmalonic acid and homocysteine concentrations in finding patients with cobalamin deficiency is limited by the fact that kidney function influences the results. Ten per cent of the patients did develop true cobalamin deficiency. A postoperative vitamin B12 value below 200 pmol/l indicates a 50% risk of later cobalamin deficiency. CONCLUSIONS: The construction of a Kock reservoir does not per se cause cobalamin deficiency. Substitution should be instituted at a postoperative concentration below 200 pmol/l. PMID- 11771866 TI - Renovascular hypertension in children. AB - OBJECTIVE: To study the etiology, clinical spectrum. image findings, management and outcome of children with renovascular hypertension (RVH). MATERIAL AND METHODS: Twenty children (aged 5 days to 15 years) were studied and treated for RVH during 1977-1998. In 14 cases hypertension was found during a routine examination. Six cases had heart failure and/or hypertensive encephalopathy. Diagnosis was made with aortography. Post-captopril renography and Doppler ultrasonography were obtained in 8 patients and spiral computed tomography angiography in 2. Treatment consisted of surgery (8 patients), percutaneous transluminal angioplasty (PTA) (5) or antihypertensive drugs only (8). RESULTS: Initial blood pressure was 62 +/- 31 mmHg > 95th percentile for systolic and 44 +/- 22 mmHg for diastolic blood pressure. Twelve children had unilateral and 8 had bilateral arterial stenosis. In 3 cases lesions were intrarenal. RVH was due to fibromuscular dysplasia (7 patients) and associated to middle aortic syndrome (5). neurofibromatosis (3), William's syndrome (2). Takayasu's arteritis (1) and pheochromocytoma (1). Treatment of choice was decided depending on the size of the child and location and severity of the stenosis. At the end of the follow-up (78 +/- 49 months), 9 patients are normotensive without medication and 7 are normotensive with drugs. Three patients have died, 2 for unrelated causes and I for cardiac failure; 1 child was lost to the follow-up. CONCLUSIONS: Although symptoms are relatively uncommon. renovascular disease is a frequent cause of severe hypertension in childhood. Non-invasive diagnostic techniques appear useful as screening methods. Treatment by surgery or PTA is successful if patients are carefully selected. PMID- 11771867 TI - Sympathetic nervous system overactivity in hypertensive patients with chronic renal failure--role of upright body position. AB - OBJECTIVE: The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys. MATERIAL AND METHODS: Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions. RESULTS: Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p < 0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p < 0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p < 0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p < 0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p > 0.10). Plasma NE correlated positively with MAP (p < 0.001) and negatively with GFR (p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p < 0.05). CONCLUSION: Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients. PMID- 11771868 TI - Wegener's granulomatosis: inflammatory cells and markers of repair and fibrosis in renal biopsies--a clinicopathological study. AB - OBJECTIVE: This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegener's granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis. MATERIAL AND METHODS: Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, alpha-smooth muscle actin (alpha-SMA) and vimentin was done. RESULTS: The dominating intraglomerular leucocytes were macrophages (29.9 +/- 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 +/- 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8+ (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial alpha-SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage. CONCLUSIONS: Evidence was found for a cellular type IV immune response in WG, with CD8+ T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial alpha-SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy. PMID- 11771869 TI - Abnormal rheology in cyanotic congenital heart disease--a factor in non-immune nephropathy. AB - OBJECTIVE: There are few data on non-immune nephropathy in cyanotic congenital heart disease reported in the literature. Rheologic changes have been suspected to be involved in the pathogenesis. This study was performed to describe the characteristics of renal functional and hemorheological abnormalities in a large group of patients with cyanotic congenital heart disease. PATIENTS AND METHODS: Thirty-five cyanotic patients with median oxygen saturation of 82% (range 38 92%), age 18 years (range 5-63 years), and 13 acyanotic controls with atrial septal defect, age 37 years (range 20-66 years) were included. Red cell indices, blood and plasma viscosity were analyzed. Renal function was evaluated with measurements of albumin, alpha1-microglobulin, transferrin, immunoglobuline, and N-acetyl-beta-D-glucosaminidase in the urine. RESULTS: Fifteen cyanotic patients and 1 control patient had pathologic albuminuria (p < 0.05). In cyanotic patients blood and plasma viscosity, erythrocyte count, hemoglobin, and hematocrit were elevated while mean corpuscular volume and mean corpuscular hemoglobin were decreased (p < 0.05). The possible impact of blood hyperviscosity on proteinuria is indicated by multiple regression analysis (odds ratio = 0.5, confidence intervals 22-130, p < 0.05). CONCLUSIONS: Our study shows a coincidence of elevated blood viscosity and proteinuria in patients with cyanotic congenital heart disease. This observation supports the hypothesis that impaired peritubular capillary blood flow with increased intraglomerular blood pressure may add to chronic glomerular dysfunction. PMID- 11771870 TI - Transitional cell carcinoma in the ileal conduit following radical cystectomy and nephroureterectomy. AB - We report a case of transitional cell carcinomas (TCCs) at the terminal of ileal conduit and right ureteroileal junction after cystectomy and left nephroureterectomy. When upper urinary tract tumor occurs after cystectomy with ileal conduit, it is necessary to beware of the recurrence of TCC in the ileal conduit. PMID- 11771871 TI - High flow priapism due to a bilateral arteriosinusoidal fistula--an unusual conservative treatment. AB - The authors report a rare case of high flow priapism due to a bilateral arteriosinusoidal fistula conservatively treated. Twenty months after the treatment the patient claimed to have a normal sexual activity. PMID- 11771872 TI - Implantation metastasis in ureter from a colonic adenocarcinoma. AB - Metastasis to the ureter is very rare. In most published cases, the diagnosis is only made at postmortem examination or when gross metastasis is present. This report presents a case in which the metastasis from a colonic tumour occluded the ureteral lumen from inside. PMID- 11771873 TI - Massive mediastinal seminoma post-orchidectomy--late relapse with skip-metastases or new primary? AB - A case of a massive, biopsy-proven, advanced seminoma in the mediastinum 12 years after orchidectomy for a malignant right-sided testicular tumour of unknown histology is presented. The highly unusual nature of this presentation is discussed and may represent either late relapse from skip-metastases or metachronous gonadal and extragonadal tumour development. Immunohistochemical staining was unable to distinguish the site of origin of the lesion. PMID- 11771874 TI - Leiomyosarcoma of the renal pelvis. AB - We report a case of renal leiomyosarcoma arising from the renal pelvis with immunohistochemical confirmation of the diagnosis. In this instance clinical presentation and imaging finding are not helpful in accurately establishing the diagnosis preoperatively. Wide surgical excision would appear to be the treatment of choice. PMID- 11771875 TI - Solitary contralateral renal pelvis metastasis 9 years after removal of renal adenocarcinoma. AB - Extremely rarely, renal cell carcinoma metastasizes to the contralateral renal pelvis or ureter. The present report concerns a case where a metastatic tumour was successfully removed from the left renal pelvis 9 years after right nephrectomy for the primary tumour. PMID- 11771876 TI - Metachronous contralateral germ cell tumor 7 years after management of testicular intraepithelial neoplasia by chemotherapy and multiple control biopsies. AB - We report about a metachronous germ cell tumor 7 years after chemotherapy of advanced testicular cancer and contralateral testicular intraepithelial neoplasia (TIN). Chemotherapy can not safely eradicate TIN. The safest treatment for TIN remains low dose radiation. PMID- 11771877 TI - From chicken coops to genome maps: generating phenotype from the molecular blueprint. AB - The tools of molecular and cellular biology can be used to precisely describe traits in terms of a sequence of nucleic acids when their molecular and cellular bases are well understood. The entire genome of elite production birds, however, cannot be written as a series of A's, T's, C's, and G's because the interaction between alleles at the same and different loci is too large and there is likely to be many genotypes that encode the same production trait phenotype. A first draft of the genetic map of the chicken is anticipated within the next few years, but a complete molecular description of the genome of birds with elite production characteristics is not anticipated in the near future. Quantitative genetics will remain the cornerstone of breeding programs for production traits. Novel sequences encoding traits such as enhanced nutritional capability (e.g., expression of phytase) and resistance to specific diseases could be introduced into lines of chickens using the tools of molecular and cellular biology. Cloning could be used by the poultry industry to disperse highly desirable genotypes without the need for grandparent and parent flocks for multiplication. PMID- 11771878 TI - Thermotolerance acquisition in broiler chickens by temperature conditioning early in life--the effect of timing and ambient temperature. AB - Thermal conditioning of chicks results in improvements in performance and thermotolerance at marketing age. Conditioning has been found to be a sensitive process, dependent on age and the temperature used. The objective of this study was to assess the optimal timing and temperature for the conditioning processes. Six separate trials were conducted on male broiler chickens: the first two aimed to find the optimal age for thermal conditioning (1 to 5 d of age); the other four evaluated the optimal thermal conditioning temperature between 36 and 40.5 C. At 42 d of age chickens were thermally challenged to evaluate their ability to cope with acute heat stress. The highest body weight was achieved when thermal conditioning had been applied at the age of 3 d, and it coincided with low feed intake and higher to significantly higher feed efficiency. These treated chickens showed relatively lower mortality rate under thermal challenge and lower to significantly lower Triiodothyronine (T3) concentration in Trial 2. Chicks that had been thermally conditioned at ambient temperatures (Ta) of 36 and 37.5 C at the age of 3 d demonstrated the best performance characteristics and the ability to reduce T3 concentration to the lowest levels during thermal challenge. It can be suggested, therefore, that a Ta between 36.0 and 37.5 C, applied at 3 d of age is optimum for thermal conditioning of broiler chickens. PMID- 11771879 TI - Effects of storage length and weight loss during incubation on the hatchability of ostrich eggs (Struthio camuelus). AB - A total of 150 ostrich eggs was collected from two commercial ostrich farms. The eggs were brushed to remove soil and placed into one storage area (15.51 to 15.56 C without controlling humidity) for different periods of time (up to 19 d) before being incubated. After storage, the eggs were kept for 12 h at room temperature, and then washed, disinfected, and dried before being placed into a commercial incubator to determine the effect of length of storage on hatchability. The two supply farms varied by 11.1% in hatchability. The weight of eggs stored for the same lengths of time was not significantly different (P > or = 0.05) between hatched and unhatched eggs. Hatchabilities of ostrich eggs were not affected by days of storage up to 19 d at 15.51 to 15.56 C without controlling the humidity level but, rather, by the amount of weight loss during incubation. PMID- 11771880 TI - Selection of genetically modified chicken blastodermal cells by magnetic activated cell sorting. AB - The use of chicken blastodermal cells (CBC) in the production of transgenic chickens requires incorporation of the desired stable genetic modification into CBC. With greater proportions of stably transfected blastodermal cells in the embryo inoculum, the frequency of intermediate chimeric birds is greater. Magnetic-activated cell sorting (MACS) was evaluated as a method for enrichment of transfected CBC. This approach requires surface expression of a molecule that can be recognized by an antibody. Chicken blastodermal cells from fertilized Barred Plymouth Rock eggs were coelectroporated with pmiwZ and pMACS Kk and were sorted magnetically by expression of the mouse H-2Kk molecule on the surface of successfully transfected cells. The effectiveness of sorting was assessed using X gal staining to detect lacZ expression from the pmiwZ plasmid. After 48 h of culture, lacZ-positive cells appeared to be enriched 1.4-fold in the MACS selected population. Cells from this enriched pool contributed to extra-embryonic and intra-embryonic tissues of 72-h White Leghorn recipient embryos with a marginal increase in levels of intra-embryonic contribution. Our demonstration that transfected, cultured, and magnetically sorted CBC maintain their ability to contribute to ectodermal and mesodermal lineages of intra-embryonic tissues illustrates the potential value of this technique for introducing genetic modifications into birds. PMID- 11771881 TI - Candidate gene promoter polymorphisms and antibody response kinetics in chickens: interferon-gamma, interleukin-2, and immunoglobulin light chain. AB - An F2 population was produced from mating G0 highly inbred (>99%) males of two MHC-congenic Fayoumi lines with G-B1 Leghorn hens. The F2 population was essentially a full-sibship with the F1 sire line reflecting MHC effect. Adult F2 hens (n = 158) were injected twice with SRBC and whole fixed Brucella abortus (BA). Agglutinating antibody titer at 7 d after primary immunization and mean titer of the final three samples (Days 18, 32, and 63 after the second immunization) were used as parameters for primary and equilibrium phases, respectively. Secondary phase parameters of minimum (Ymin), maximum titers (Ymax) and time needed to achieve minimum (Tmin) and maximum (Tmax) titers were estimated from seven postsecondary titers with a nonlinear regression model. Three candidate genes, interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and immunoglobulin G light chain (IgL) were studied. Primers for the promoter regions were designed from EMBL chicken genomic sequences. Polymorphisms between parental lines were detected by direct sequencing. Polymerase chain reaction-restriction fragment length polymorphism methods were then developed to directly detect the polymorphism. There were significant main effects (P < 0.05, general linear model analysis) of IFN-gamma polymorphism on Ymax of BA antibody and interaction of IFN gamma by IgL on primary antibody response to SRBC and BA, and on Tmin and Ymin of antibody response to SRBC in F2 offspring of M5.1 grandsires. There were significant main effects of IFN-gamma polymorphism on Tmax of BA and interaction of IFN-gamma by IL-2 on Ymin to SRBC in F2 offspring of M15.2 grandsires. The results suggest that IFN-gamma genes play an important role in chicken primary and secondary antibody response to SRBC and BA antigens, and there exists interaction among genes for antibody production. PMID- 11771882 TI - Molecular cloning and expression of turkey inhibin-alpha and -betaA subunits. AB - We isolated cDNA encoding turkey inhibin-alpha (tINH-alpha) and -betaA (tINH betaA) subunits from the turkey ovary using reverse transcription-polymerase chain reaction (RT-PCR). The isolated alpha subunit and betaA subunit included the entire open reading frames encoding 329 and 424 amino acids, respectively. The amino acid sequences of mature tINH-alpha subunit and tINH-betaA subunit (12.6 and 12.9 kDa proteins, respectively), established via DNA sequence analysis, were highly conserved between the chicken and various mammals. Northern blot analysis revealed that the transcripts of tINH-alpha and tINH-betaA subunits were approximately 1.7 and 8.4 kb, respectively. In various stages of follicular development, tINH-alpha mRNA was highly expressed in small white follicles as compared to postovulatory and regressed follicles, whereas tINH-betaA mRNA was predominately expressed in preovulatory F5 follicles. PMID- 11771883 TI - Effects of added dietary fat and phosphorus on the performance and egg quality of laying hens subjected to a constant high environmental temperature. AB - Two experiments were conducted to study the combined effect of nonphytate P (NPP), fat, and temperature on the performance and egg quality of hens pre- and postpeak. In Experiment 1, 192 Single Comb White Leghorn layers, aged 22 wk, were individually housed in cages under ambient (AT) and constant high temperature (CHT) of 33 +/- 1 C. In Experiment 2, 28-wk-old birds were used with a CHT of 35 +/- 1 C. Diets contained 0 and 4% added vegetable fat with four dietary NPP levels, ranging from 0.20 to 0.50% in Experiment 1 and from 0.15 to 0.45% in Experiment 2, at increments of 0.1%. These diets were fed to hens for 84 d. Performance and egg quality criteria were measured in both experiments, whereas serum and tibia Ca and P were determined in Experiment 2. Results showed that there was no significant interaction among NPP, fat, and temperature, for any criteria measured. The CHT significantly reduced BW, feed intake, egg production, egg weight, egg mass, and shell thickness. Moreover, it decreased (P < 0.05) serum Ca, P, tibia ash, and tibia P. The lowest NPP levels resulted in the greatest shell thickness (P < 0.05), which decreased with increasing NPP levels in both trials. In the postpeak experiment, the feed intake was significantly reduced by 0.15 and 0.25% NPP. Moreover, 0.15% NPP significantly reduced egg production as compared to 0.35 and 0.45% NPP diets. Levels between 0.25 and 0.45% significantly improved the serum phosphorus content as compared to 0.15%. Added fat improved only serum P level (P < 0.05). The beneficial effect of supplemental fat on hen performance was evident in Experiment 1 but not in Experiment 2, indicating that nutrients were oriented more toward supporting egg production rather than maintaining the BW at the postpeak stage. PMID- 11771884 TI - Effects of dietary 1,4-diaminobutane (putrescine) on eggshell quality and laying performance of hens laying thin-shelled eggs. AB - Experiments were conducted to evaluate the potential for dietary 1,4 diaminobutane (putrescine) to influence eggshell quality and overall laying performance in hens. Forty-eight, 60-wk-old White Leghorn hens laying thin shelled eggs were fed a corn and soybean meal-based diet supplemented with 0.00 (control), 0.05, 0.10, or 0.15% putrescine for 4 wk. Twelve hens that laid thick shelled eggs were also fed the control diet. The feeding of supplemental putrescine decreased feed consumption; however, egg weight decreased only at higher levels of supplementation. Increasing dietary levels of putrescine responded quadratically in eggshell deformation, eggshell weight, and eggshell weight as a percentage of egg weight (P < 0.05). There were no significant differences in shell deformation, shell thickness, or shell weight when comparing hens laying thick-shelled eggs and those laying thin-shelled eggs that were fed 0.05% supplemental putrescine. Calcium intake, calcium retention, and calcium balance decreased linearly (P < 0.05) with increasing levels of dietary putrescine. Pancreatic putrescine concentrations were significantly higher (P < 0.05) in hens laying thick-shelled eggs compared with hens laying thin-shelled eggs. It appeared that pancreatic cells synthesized more polyamines in hens laying thick-shelled eggs. This increase in polyamines might have caused improved eggshell quality by increasing calcium transport. It was concluded that 0.05% supplemental putrescine improved eggshell quality; however, higher levels proved to be toxic. PMID- 11771885 TI - Threonine requirements of different broiler genotypes. AB - The objectives of this work were to study the responses of one Leghorn and two broiler stocks and sexes to different levels of Thr and to estimate their requirements for this amino acid. All experiments were conducted with birds from 1 to 18 d of age. Body weight gain (BWG) and feed consumption were measured on the eighteenth day, and feed conversion ratio (FCR) was calculated. At Day 18, three birds per replicate were killed, and liver and fat pads were collected and weighed. The data were analyzed by the general linear model and nonlinear model procedures of SAS software, and the broken-line linear model was used to estimate Thr requirements of chicks. Experiment 1 had a 5 x 3 factorial design with five levels of Thr (0.63, 0.70, 0.77, 0.84, and 0.91% of the diet), two broiler genotypes (Arbor Acres Classic and High Yield), and one Leghorn genotype (Hy-line W-36), with three replicate pens of eight male birds each. The basal diet was composed of corn, peanut meal (PNM), poultry by-product meal, poultry fat, DL Met, L-Lys, and L-Ile (23% CP and 3.2 kcal/g of ME). The Leghorn chicks did not respond to Thr supplementation, indicating their requirement was < or = 0.63%. High Yield birds had better BWG and FCR than Classic. The BWG and FCR were reduced more in Classic than High Yield strains by the lowest Thr level. The percentage of liver was higher in the Classic than High Yield strain broilers with Thr supplementation. The second experiment (2 x 2 x 2 factorial design) was conducted to evaluate the effects of two levels of Thr (0.63 and 0.90%), two levels of Ile (0.72 and 0.90%), and two broiler strains (as Experiment 1). There were no responses to Ile for any parameters measured. Experiment 3 (6 x 2 factorial design, corn, PNM-based basal diet) had six Thr levels (0.63, 0.67, 0.71, 0.75, 0.79, and 0.83%) and two broiler strains (as Experiment 1), with four replicate pens of eight male birds each. The High Yield strain broilers grew significantly better at the lowest Thr level, but performance was similar at the higher Thr levels (significant interaction, P = 0.018). FCR was affected by Thr level but not by strain. The Thr requirement of the Classic strain broilers was 0.69 +/- 0.01% for BWG and 0.68 +/- 0.01% for FCR. The Thr requirement of the High Yield strain broilers was 0.68 +/- 0.01% for BWG and 0.69 +/- 0.01% for FCR. The Thr requirements of male versus female High Yield strain broilers were evaluated in a 6 x 2 factorial design, with six Thr levels (Experiment 4), with four replicate pens of eight birds each. Males and females had the same performance and carcass composition results (P > 0.05), except for percentage abdominal fat pads. The Thr requirement was 0.71 +/- 0.01% for BWG and 0.71 +/- 0.01% for FCR for the males and 0.72 +/- 0.008% for BWG and 0.71 +/- 0.001% for FCR for females. Excellent performance was observed from the corn- and PNM-based diet supplemented to contain 0.72% Thr. The Thr requirements of High Yield and Classic broilers (males and females) were similar and greater than for the Leghorn strain studied. PMID- 11771886 TI - Tryptophan requirements of different broiler genotypes. AB - Two experiments were conducted with broiler chicks in battery brooders from 1 to 18 d of age to determine Trp requirements and to evaluate the performance of different genotypes (classic vs. high yield and male vs. female). Experiment 1 was a 6 x 2 factorial experiment, with six levels of Trp (0.09, 0.12, 0.15, 0.18, 0.21, and 0.24% of the diet) and two broiler chicken strains (male Arbor Acres Classic and Arbor Acres High Yield). Experiment 2 was a 6 x 2 factorial design with the same levels of Trp as in Experiment 1 and two sexes (males and females); Ross x Ross 308 birds were used. Both experiments had four replicate pens of eight birds each per treatment. The basal diet was based on corn (70.79%), corn gluten meal (17.44%), and gelatin by-product and poultry fat (23% of CP and 3.34 kcal/g of ME). At 18 d of age, three birds per replicate were killed, and livers and fat pads were removed. The broken-line linear model was used to estimate the chicks Trp requirement. Liver or liver fat and fat pad weights (as a percentage of body weight) were affected by dietary Trp level. In Experiment 1, the Trp requirements differed little; for gain they were 0.18 +/- 0.002% and 0.17 +/- 0.002%, and for feed conversion they were 0.16 +/- 0.004% and 0.16 +/- 0.002%, for the Classic and High Yield broilers, respectively. In Experiment 2, the Trp requirement of males was 0.17 +/- 0.003% for BW and 0.17 +/- 0.003% for feed conversion, and that of females was 0.17 +/- 0.003% for body weight and 0.16 +/- 0.001% for feed conversion. There was no apparent difference in the Trp requirement of young broilers due to genetic stock or gender (P > 0.05). PMID- 11771887 TI - Supplementary dim light differentially influences sexual maturity, oviposition time, and melatonin rhythms in pullets. AB - The addition of two 3-h periods of very dim light, one before and one after a normal 8-h photoperiod, advances sexual maturity in pullets by about a week. This trial tested the hypothesis that dim light given before a short day of normal intensity is linked to form a more stimulatory day length and that dim light given after it is photosexually ignored. Pullets were reared from 2 d of age on 8 h photoperiods. From 10 wk, they were continued on 8-h photoperiods, transferred to 16 h, or given an 8-h period of dim light (0.09 lx) immediately before or after the main 8-h photoperiod. The bright/dim and dim/ bright groups matured at the same age, thus disproving the hypothesis tested. Both groups matured 1 wk earlier than the 8-h controls but 5 wk later than birds transferred to 16-h photoperiod. Oviposition time was similar for 8-h controls and bright/dim hens and delayed by 3 h for 16-h birds, but phase advanced by 2.4 h for dim/bright hens. Plasma melatonin rhythm was phase-advanced by about 5 h in the dim/bright hens and retarded by about 5 h in the bright/dim hens, suggesting a 13-h subjective day. However, these treatments were not regarded as fully stimulatory, as a transfer to a normal 13-h photoperiod at this age advances maturity by 5 to 6 wk. These findings show that the addition of a period of dim light to a normal nonstimulatory photoperiod differentially affects the clocks that control sexual maturation, plasma melatonin concentration, and oviposition time. PMID- 11771888 TI - Egg storage effects on plasma glucose and supply and demand tissue glycogen concentrations of broiler embryos. AB - The hypothesis was tested that enhanced embryonic carbohydrate metabolism may enable embryos to survive egg storage effects. As lines of broiler breeders age, some lines resist detrimental effects of egg storage on embryonic survival, whereas others do not. Fertile eggs were obtained from two lines differing in storage ability. Eggs from each line by age group were stored for 1 or 14 d prior to setting. Eggs were distributed randomly into a single machine and incubated under standard conditions. Beginning at 17 d of incubation, immediately prior to the plateau stage in oxygen consumption, embryos from each of the treatment groups were sampled for BW, organ growth, glycogen concentration, and plasma glucose concentrations. Sampling continued through hatching. Plasma glucose concentrations increased significantly, and hepatic glycogen concentrations declined as embryos approached hatching. The rate at which glycogen was accrued into muscle and heart tissue displayed a significant three-way interaction among line, age, and storage. Embryos from the line that resisted storage mortality maintained greater glycogen concentrations in muscle and heart tissues than those from the line and age with diminished survival rates. It was concluded that embryonic survival rates differ following egg storage because of the ability of the embryo to accrue and maintain adequate carbohydrate for growth and function of vital demand tissues. PMID- 11771889 TI - Effects of adrenergic agonists on glycogenolysis in primary cultures of glycogen body cells and telencephalon astrocytes of the chick. AB - The glycogen body (GB) is at the dorsal area of the lumbosacral spinal cord in birds and is composed of uniform cells that are characterized by high-glycogen storage. Previous morphological and embryological examinations suggest that the GB is derived from the neuroepithelium and contains many blood vessels and a few nerve fibers. However, the function of the GB and role of the glycogen are unknown. Mammalian astrocytes are major sites for glycogen stores in the central nervous system. The metabolic features of astrocytes have been defined by using cultured cells. As a first step toward investigating the function of GB, we established primary culture of chicken GB cells and telencephalon astrocytes. The cultured GB cells maintained high glycogen content and glial fibrillary acidic protein (GFAP) in the cytoplasm. The glycogen content of GB cells significantly increased with the glucose concentration in the medium. The effects of adrenergic agonists on glycogenolysis were different between GB cells and telencephalon astrocytes. The telencephalon astrocytes shared similar characteristics of glycogenolysis with mouse astrocytes, which are mainly affected by beta adrenergic receptor. Although GB cells were affected by noradrenalin (both alpha and beta adrenergic agonist), they were not affected by beta adrenergic agonist. These results showed that cultured GB cells were considered as one lineage of astrocytes because of their reactivity to antibody against GFAP; however, the metabolic features of GB cells were different from those of telencephalon astrocytes. PMID- 11771890 TI - Low score normal muscle weakness alters cardiac decorin expression: implication for cardiac collagen fibril organization. AB - Cardiac decorin and Type I collagen expression and collagen fibrosis were examined in a chicken line exhibiting the low score normal (LSN) genetic muscle weakness and compared to normal cardiac muscle at 14 and 20 d of embryonic development and at 1 and 6 wk posthatch. These extracellular matrix proteins were selected due to their role in regulating tissue elasticity, which is critical for normal cardiac function. Beginning at 1 wk posthatch, relative levels of decorin were higher in the LSN cardiac muscle than in the control, indicating a time dependent increase in decorin expression. Type I collagen levels appeared to be unaffected by the LSN condition. Morphologically, myocardial and coronary artery fibrosis did not differ between the control and LSN at all stages examined. These results are suggestive of extracellular matrix remodeling in LSN cardiac muscle that is mediated through a decorin-dependent pathway. PMID- 11771891 TI - Volatiles, color, and lipid oxidation of broiler breast fillets irradiated before and after cooking. AB - Chicken breast fillets were equally divided into three groups. One group was vacuum packaged, cooked in a water bath (cooked-in-bag) at 82 C for 25 min, and then irradiated at 0 or 3 kGy with a linear accelerator (V-C-I). The other two groups were irradiated at 0 or 3.0 kGy in vacuum packaging (V-I-C) or aerobic packaging (A-I-C). After 3 d of storage at 4 C, the irradiated meats were cooked in a water bath (cooked-in-bag) at 82 C for 25 min. After being cooked, meats were repackaged under vacuum and stored at 4 C. Breast fillets were analyzed at 0 and 21 d after cooking and analyzed for lipid oxidation, color, and volatiles. Irradiation accelerated lipid oxidation of breast fillets. Three days of storage of raw meat in aerobic conditions after irradiation had only minor influences on lipid oxidation after cooking. However, irradiation had a significant effect on the volatile production in meat. Dimethyl disulfide, related to irradiation odor, was significantly higher in irradiated fillets than in nonirradiated fillets for V-C-I and V-I-C, whereas it was only slightly higher for A-I-C. Other volatiles, such as 3-methyl butanal and 2-methyl butanal, were also produced in significant amounts after irradiation, especially in V-C-I and V-I-C. These results showed that irradiating cooked meat induced slightly more changes in volatiles than irradiating raw meat and then cooking. The amount of dimethyl disulfide between irradiated and nonirradiated samples for A-I-C was not different, because the dimethyl disulfide produced by irradiation disappeared during the 3 d in aerobic storage before cooking. Color a* value of irradiated fillets was higher than that of nonirradiated fillets. Irradiation also induced color L* and b* value changes. After 3 d of aerobic storage after irradiation of raw meat, the influence of irradiation on color after cooking was reduced. No significant lipid oxidation occurred during storage as shown by the low values for TBA-reactive substances. PMID- 11771892 TI - Contribution of cumulus cells and serum to the maturation of oocyte cytoplasm as revealed by intracytoplasmic sperm injection (ICSI). AB - The fertilisability and developmental capacity of mouse oocytes matured in vitro were examined by in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). While more than 50% of cumulus-enclosed oocytes were fertilised by IVF after maturation in serum-supplemented medium, none were fertilised when the oocytes matured without serum. By ICSI, the majority (78-94%) of the oocytes were fertilised regardless of the presence or absence of serum in oocyte maturation media. Although the majority (88-92%) of cumulus-free germinal vesicle oocytes underwent nuclear maturation in both serum-free and serum-containing media, those matured in the presence of serum were more readily fertilised by ICSI (43%) than those matured without it (3-5%). The cumulus-free oocytes co cultured with cumulus cells but without serum were fertilised at 36%, suggesting some secreted factor promotes the oocyte's cytoplasmic maturation. The oocytes fertilised by ICSI developed into normal-term fetuses regardless of the presence or absence of serum or cumulus cells in oocyte maturation medium. These results lead us to conclude that (a) the cytoplasm of the oocytes can mature in serum free medium and (b) the presence of both the serum and the cumulus cells in the medium surrounding maturing oocytes is beneficial for the development of the fertilisation- and development-competence of oocyte cytoplasm. PMID- 11771893 TI - Glycosaminoglycan-bound and free inter-alpha-trypsin inhibitor components of follicular fluid. AB - The proteinase inhibitor inter-alpha trypsin inhibitor (ITI) is a blood-derived protein necessary for normal female fertility. Absence of ITI leads to ovulation of naked oocytes that cannot fertilise. ITI consists of two heavy chains (ITI-HC) and bikunin linked by a chrondroitin sulphate. By binding to hyaluronate, ITI-HC stabilises the extracellular matrix, but ITI-HC also binds to proteoglycans in follicular fluid. In vivo concentrations of ITI components in preovulatory follicular fluid, free as well as bound to hyaluronate or proteoglycan, are unknown. In order to quantify these components, 58 follicular fluids and 13 blood samples were collected in connection with in vitro fertilisation and embryo transfer treatment of 13 women. Quantitation of glycosaminoglycan-bound ITI-HC was performed after separation from free ITI in agarose gel. ITI components were determined by immunoelectrophoresis and hyaluronate by an ELISA method. The follicular fluid concentration of ITI was on average 70% of that in plasma and the concentration of hyaluronate remained low despite follicular production, suggesting that the production of hyaluronate is the rate-limiting step in the formation of the extracellular matrix of the oocyte-cumulus complex. In follicular fluid, the concentration of free ITI-HC was higher than that of glycosaminoglycan-bound ITI-HC. Addition of exogeneous hyaluronate doubled the amount of hyaluronate-bound ITI-HC, further supporting the notion that ITI in follicular fluid is not rate-limiting for cumulus expansion in vivo. PMID- 11771894 TI - Fast-developing preimplantation embryo progeny from heterogametic females in mammals. AB - Karyotyping and cell number estimates in preimplantation embryos from heterogametic (XY*) and homogametic (XX) females of the field mouse Akodon azarae were studied to determine whether XX-XY-XY* differences exist in the rate of preimplantation development. At the morula stage, XY embryos from heterogametic mothers had twice the mean number of cells compared with XX embryos. However, this difference in cell numbers was not seen between XX and XY embryos from homogametic mothers. In this case, mean cell numbers were similar despite embryos being XX or XY. Furthermore, the mean cell number for XX and XY morulae from homogametic females was comparable to that for XX embryos from heterogametic females. It is concluded that XY* embryos (which will develop into heterogametic females) show an accelerated rate of preimplantation development. PMID- 11771895 TI - Enzyme activity in anuran spermatozoa upon induction of the acrosome reaction. AB - At the time of sperm-egg fusion in Discoglossus pictus, a large amount of electron-dense material of an unknown nature is liberated from the sperm. In the present work we studied this material in D. pictus sperm, using an assay utilising strips of autoradiographic film as a gelatin substrate for proteolytic enzymes. Upon treatment with A23187, D. pictus sperm produced a large halo on the gelatin substrate, indicating the presence of enzymes released by the sperm at the time of the acrosome reaction. In contrast, Xenopus laevis sperm did not produce halos upon treatment with A23187. The use of protease inhibitors such as TLCK, leupeptin, chymostatin, SBTI and EACA strongly suggests that the D. pictus whole acrosome contains trypsin and chymotrypsin activity while an SBTI-sensitive activity is absent in a small portion of the acrosome, possibly the anteriormost region. Furthermore, the material released at the acrosome reaction also contains an EACA-inhibited activity, indicating the presence of plasminogen activator. We conclude that D. pictus sperm release proteolytic enzyme(s) that may act at the egg surface at the time of gamete fusion. PMID- 11771896 TI - An attempt at intracytoplasmic sperm injection of frozen-thawed minke whale (Balaenoptera bonaerensis) oocytes. AB - Little is known about the characteristics of fertilisation events in minke whales. Cryopreserved minke whale oocytes and spermatozoa do not fertilise in a standard IVF. This study was conducted to investigate the pronucleus formation ability of cryopreserved minke whale oocytes and their subsequent development following intracytoplasmic sperm injection (ICSI). In experiment 1, frozen-thawed minke whale immature oocytes were cultured for in vitro maturation (IVM) in a maturation medium (TCM199) supplemented with either porcine follicle stimulating hormone (pFSH)/estradiol-17beta (E2) or pregnant mare's serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG). After 120 h of IVM, oocyte survival was examined before ICSI, and showed no significant difference in morphological normality (24-36%) between the two IVM media. Two-cell embryos (two oocytes from 21 sperm-injected oocytes) were obtained when the maturation medium was supplemented with pFSH/E2 or PMSG/hCG. In experiment 2, cryopreserved maturing oocytes were investigated for the effects of repeat-culture (2 h or 24 h) on survival before ICSI. Pronuclear formation and development were examined for the effects of sperm pretreatment with dithiothreitol (DTT) and oocyte activation with ethanol at ICSI. A frequency of 49-69% of frozen-thawed maturing oocytes was used for ICSI. Although oocyte activation did not produce a significant difference in survival, pronucleus formation and embryonic development, 2- and 4 cell cleaved oocytes were observed after injection of sperm pretreated with DTT. PMID- 11771897 TI - Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, reversibly inhibits chromatin condensation during in vitro maturation of porcine oocytes. AB - In the present study the effects of roscovitine on the in vitro nuclear maturation of porcine oocytes were investigated. Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, prevented chromatin condensation in a concentration-dependent manner. This inhibition was reversible and was accompanied by non-activation of p34cdc2/histone H1 kinase. It also decreased enzyme activity of MAP kinase, suggesting a correlation between histone H1 kinase activation and the onset of chromatin condensation. The addition of roscovitine (50 microM) to extracts of metaphase II oocytes revealed that the MAP kinase activity was not directly affected by roscovitine, which indicates a possible link between histone H1 and MAP kinase. Chromatin condensation occurred between 20 and 28 h of culture of cumulus-oocyte complexes (COCs) in inhibitor-free medium (germinal vesicle stage I, GV1: 74.6% and 13.7%, respectively). Nearly the same proportion of chromatin condensation was detected in COCs incubated initially in inhibitor-free medium for 20-28 h and subsequently in roscovitine supplemented medium (50 microM) for a further 2-10 h (GV I: 76.2% and 18.8%, respectively). This observation indicates that roscovitine prevents chromatin condensation even after an initial inhibitor-free cultivation for 20 h. Extending this initial incubation period to > or = 22 h led to an activation of histone H1 and MAP kinase and increasing proportions of oocytes exhibiting chromatin condensation in the presence of roscovitine. It is concluded that histone H1 kinase is involved in the induction of chromatin condensation during in vitro maturation of porcine oocytes. PMID- 11771898 TI - Expression of PCNA in the testis of the lizard, Podarcis s. sicula: an endogenous molecular marker of mitotic germinal epithelium proliferation. AB - Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid metabolism as a component of the replication and repair machinery. This protein encircles DNA and can slide bidirectionally along the duplex binding to DNA polymerase delta and epsilon. It is well known that PCNA interacts with proteins involved in the cell cycle. The PCNA interactions with different cellular proteins and the importance of these interactions are discussed. To examine mitotic germinal epithelium proliferation during annual discontinuous spermatogenesis in the lizard Podarcis s. sicula, temporal and the spatial PCNA expression were investigated, and provide a useful endogenous molecular marker. PMID- 11771899 TI - Effects of the addition of glutathione during maturation on in vitro fertilisation of prepubertal goat oocytes. AB - Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is a ubiquitous intracellular free thiol that improves development of the male pronucleus at fertilisation and has also been implicated in promoting the development of preimplantation embryos. The objective of this study was to evaluate the effects of adding GSH or cysteine to the in vitro maturation medium on intracellular GSH amounts after in vitro maturation and fertilisation of prepubertal goat oocytes. Oocytes were matured in TCM199 medium supplemented with 10% bovine fetal serum, 1 mg/ml 17beta-estradiol, 10 microg/ml o-FSH, 10 microg/ml LH and 50 mg/ml gentamicin. In vitro maturation medium was completed with two independent treatments: GSH at different concentrations (0, 0.25, 0.50 and 1.00 mM) and L-cysteine at different concentrations (0, 150, 300, 600 and 900 microM). After 27 h of culture at 38.5 degrees C in 5% CO2 in air, the nuclear stage was evaluated. Simultaneously, another sample of oocytes was frozen and the intracellular GSH level was evaluated with spectrophotometric methodology. Oocytes were inseminated with fresh semen (2-3 x 10(6) sperm/ml) in TALP medium supplemented with 1 mg/ml hypotaurine. Oocytes were fixed at 20 h post-insemination to evaluate the in vitro fertilisation. Oocytes matured in 1.00 mM GSH-supplemented medium exhibited higher amounts of intracellular GSH (3.23 pmol per oocyte). The percentage of normal fertilisation (17-27%) was similar for the treatment groups. In conclusion, the addition of 1.00 mM GSH to the maturation medium could be a useful method for increasing the intracellular GSH levels of prepubertal goat oocytes. However, this increase was not associated with a higher normal fertilisation rate of prepubertal goat oocytes. PMID- 11771900 TI - Effect of incubation temperature on in vitro maturation of porcine oocytes: nuclear maturation, fertilisation and developmental competence. AB - The present study examined the effect of low culture temperature during in vitro maturation (IVM) of pig oocytes on their nuclear maturation, fertilisation and subsequent embryo development. In experiment 1, oocytes were cultured at 35 or 39 degrees C for 44 h in modified tissue culture medium 199 supplemented with 10 ng/ml epidermal growth factor, 0.57 mM cysteine, 75 microg/ml potassium penicillin G, 50 microg/ml streptomycin sulphate, 0.5 microg/ml LH and 0.5 microg/ml FSH to examine the nuclear maturation status. In experiment 2, oocytes were cultured at 35 degrees C for 44 or 68 h and nuclear maturation was examined. In experiment 3, oocytes matured for 44 or 68 h at 39 degrees C and for 68 h at 35 degrees C were co-incubated with frozen-thawed spermatozoa for 5-6 h. Putative embryos were transferred into North Carolina State University (NCSU) 23 medium containing 0.4% bovine serum albumin. At 12 h after insemination, some oocytes were fixed to examine the fertilisation rate and the remaining embryos were examined at 48 and 144 h for cleavage and blastocyst formation rate, respectively. Compared with 39 degrees C, culture of oocytes at 35 degrees C for 44 h significantly (p < 0.05) reduced the metaphase II (M II) rate (79% vs 12%). However, extension of culture time to 68 h at 35 degrees C significantly increased (p < 0.05) the M II rate (7% vs 58%). In experiment 3, compared with other groups, fewer (p < 0.05) oocytes reached M II when cultured at 35 degrees C for 68 h (69-81% vs 49%). Extension of culture duration to 68 h at 39 degrees C stimulated spontaneous activation (28%) of oocytes. No difference in cleavage rates was observed among different groups. Compared with oocytes matured for 44 h at 39 degrees C (31%), the proportion of blastocysts obtained was low (p < 0.05) for oocytes matured at 35 degrees C (13%) or 39 degrees C (3%) for 68 h. The results indicate that lower culture temperature can delay nuclear maturation of pig oocytes. However, extension of culture time can stimulate nuclear maturation and these oocytes are capable of fertilisation and development to the blastocyst stage at moderate rates. PMID- 11771901 TI - Development of porcine embryos and offspring after intracytoplasmic sperm injection with liposome transfected or non-transfected sperm into in vitro matured oocytes. AB - The objective of this study was to evaluate in vitro and in vivo development of porcine in vitro matured (IVM) porcine oocytes fertilised by intracytoplasmic sperm injection (ICSI) and the possibility of producing transgenic embryos and offspring with this procedure. Activated ICSI oocytes had a higher pronuclear formation than non-activated ICSI oocytes (mean 64.8+/-17.3% vs 28.5+/-3.4%, p<0.05). When the zygotes with two pronuclei were cultured to day 2, there was no difference (p<0.05) in the cleavage rate (mean 60.0+/-7.0% vs 63.3+/-12.7%) between the two groups. The blastocyst rate in the activation group was significantly higher than that in the non-activation group (mean 30.0+/-11.6% vs 4.6+/-4.2%, p<0.05). After injection of the sperm transfected with DNA/liposome complex, destabilised enhanced green fluorescent protein (d2EGFP) expression was not observed on day 2 in either cleaved or uncleaved embryos. But from day 3, some of the embryos at the 2-cell to 4-cell stage started to express d2EGFP. On day 7, about 30% of cleaved embryos, which were in the range of 2-cell to blastocyst stage, expressed d2EGFP. However, for the IVF oocytes inseminated with sperm transfected with DNA/liposome complex, and for oocytes injected with sperm transfected with DNA/liposome complex, and for oocytes injected with DNA/liposome complex following insemination with sperm not treated with DNA/liposome complex, none of the embryos expressed d2EGFP. Sixteen day 4 ICSI embryos derived from sperm not treated with DNA/liposome complex were transferred into a day 3 recipient. One recipient delivered a female piglet with normal birthweight. After transfer of the ICSI embryos derived from sperm transfected with DNA/liposome complex, none of the four recipients maintained pregnancy. PMID- 11771902 TI - Confocal microscopy analysis of the activity of mitochondria contained within the 'mitochondrial cloud' during oogenesis in Xenopus laevis. AB - We have used ratiometric confocal microscopy and three fluorescence techniques to study the distribution and activity of mitochondria in frog oocytes during the early stages of oogenesis. Mitochondria in frog oocytes during oogenesis were characterised by a high ratio in the 'mitochondrial cloud' and perinuclear region and a low ratio in mitochondria freely dispersed within the cytoplasm. We tested whether the high ratio visualised by the three techniques represented mitochondrial membrane potential by perturbing the mitochondrial membrane potential. Carbonyl cyanide p-(trifluoromethyl)phenylhydrazone (FCCP) caused the immediate destruction of the membrane potential, and consequent loss of fluorescence from the membrane-potential-sensitive confocal channel. In contrast, nigericin caused an increase in membrane potential represented by a steady increase in fluorescence ratio. These data demonstrate that mitochondrial activity can be measured during oogenesis in frog oocytes, and suggest that the mitochondrial cloud and perinuclear regions are characterised by highly active mitochondria. PMID- 11771903 TI - Nuclear maturation inducers in Bufo arenarum oocytes. AB - The present study analyses the effect of dihydrotestosterone (DHT) and mammalian insulin on the nuclear maturation of Bufo arenarum oocytes under in vitro conditions. The response of fully grown follicle oocytes to DHT, shown by germinal vesicle breakdown (GVBD), occurred in a manner dependent on dose, time and sexual cycle period. The highest oocyte sensitivity to the hormone appeared during the breeding period, a fact evinced by high GVBD percentages after short incubation periods and at a low hormone concentrations. Insulin also proved effective in inducing nuclear maturation, although its action was only visible at high concentrations and after a long incubation period. The combination of insulin and steroid hormones (DHT or progesterone), both at subliminal doses, caused a noticeable potentiating synergism, resulting in a rapid and important increase in GVBD. Another effect of insulin was the acquisition by oocytes of steroid sensitivity during folliculogenesis. PMID- 11771904 TI - Variants of intrafamilial sexual abuse experience: implications for short- and long-term development. AB - This study examines short- and long-term maladaptive outcomes in a sample of sexually abused females and a comparison group. The sample consists of intrafamilial sexual abuse victims ages 6-16 years at entry into the study and a demographically similar comparison group. The outcomes examined included measures of behavior and psychological problems such as aggressive behavior, depression, dissociation, and low self-esteem; and measures at two time points, first at entry into the study (median age 11 years) and approximately 7 years later (median age 18 years). The specific questions being addressed were (a) whether subgroups or profiles. based on the specific characteristics of the sexual abuse experienced, can be identified in this sample of abused females; and (b) whether these profile groups predict different patterns of adverse short- or long-term outcomes. PMID- 11771905 TI - Resilience among abused and neglected children grown up. AB - Although an extensive literature has accumulated documenting the maladaptive outcomes associated with childhood victimization, a limited body of knowledge addresses resilience. This paper sought to operationalize the construct of resilience across a number of domains of functioning and time periods and to determine the extent to which abused and neglected children grown up demonstrate resilience. Substantiated cases of child abuse and neglect from 1967 to 1971 were matched on gender, age, race, and approximate family social class with nonabused and nonneglected children and followed prospectively into young adulthood. Between 1989 and 1995. 1,196 participants (676 abused and neglected and 520 controls) were administered a 2-hr in-person interview, including a psychiatric assessment. Resilience requires meeting the criteria for success across six of eight domains of functioning: employment, homelessness, education, social activity, psychiatric disorder, substance abuse, and two domains assessing criminal behavior (official arrest and self-reports of violence). Results indicate that 22% of abused and neglected individuals meet the criteria for resilience. More females met the criteria for resilience and females were successful across a greater number of domains than males. We speculate on the meaning of these findings and discuss implications for the child maltreatment field. Limitations of the study are also acknowledged. PMID- 11771906 TI - Operationalizing child maltreatment: developmental processes and outcomes. PMID- 11771907 TI - Dimensions of child maltreatment and children's adjustment: contributions of developmental timing and subtype. AB - This investigation examined the dimensions of developmental timing, subtype, and severity of maltreatment and their relations with child adaptation. The 814 children who participated in a summer day camp, 492 of whom were maltreated and 322 of whom were nonmaltreated comparison children, were assessed by camp counselors on their internalizing and externalizing symptomatology, aggressive, withdrawn, and cooperative behavior, and on personality dimensions of ego resiliency and ego control, and were rated by peers on disruptive, aggressive, and cooperative behavior. The severity within each subtype of maltreatment and the developmental period in which each subtype occurred were examined through hierarchical regression analyses. Additionally, children with similar timing or subtype patterns were grouped to explore diversity in outcomes. Results highlighted the role of severity of emotional maltreatment in the infancy toddlerhood period and physical abuse during the preschool period in predicting externalizing behavior and aggression. Severity of physical neglect, particularly when it occurred during the preschool period, was associated with internalizing symptomatology and withdrawn behavior. Additionally, maltreatment during the school-age period contributed significant variance after earlier maltreatment was controlled. Chronic maltreatment, especially with onset during infancy toddlerhood or preschool periods, was linked with more maladaptive outcomes. The implications of measuring multiple dimensions for improving research in child maltreatment are discussed. PMID- 11771908 TI - The impact of child maltreatment and psychopathology on neuroendocrine functioning. AB - Cortisol regulation was investigated in a sample of school-aged maltreated (n = 167) and demographically comparable low-income nonmaltreated (n = 204) boys and girls in the context of a day camp research program. The presence of clinical level internalizing and clinical-level externalizing symptomatology was determined through adult report and child self report. Children who exhibited clinical-level internalizing problems only, clinical-level externalizing problems only, and comorbid clinical-level internalizing and extemalizing problems were identified. Clinical-level cases were more prevalent among the maltreated children. Maltreated children with clinical-level internalizing problems were distinguished by higher morning, afternoon, and average daily cortisol levels across the week of camp attendance. In contrast, nonmaltreated boys with clinical level externalizing problems emerged as distinct in terms of low levels of morning and average daily levels of cortisol. Maltreated children with comorbid clinical-level internalizing and externalizing problems were more likely not to show the expected diumal decrease in cortisol. The findings are discussed in terms of the joint impact of maltreatment and different forms of psychopathology on neuroendocrine regulation. PMID- 11771909 TI - The effect of physical abuse on children's social and affective status: a model of cognitive and behavioral processes explaining the association. AB - This study proposes a model explaining the association between physical abuse of children and children's social and affective status as one in which children's social expectations and behavior, developed within the context of abusive parenting, mediate current functioning in these two outcome domains. Subjects included one hundred 9 to 12-year-old physically abused children recruited from consecutive entries onto the New York State Register for Child Abuse for New York City and 100 case-matched classmate nonabused comparison children. Sociometric assessments were carried out in classrooms, interviews were conducted with the children and their parents, and teachers, parents, and classmates rated the children's behavior. Path analysis was utilized to test the conceptually derived models. Children's social expectations regarding peers, and two social behaviors- aggressive behavior and prosocial behavior--were found to mediate between abuse and positive and negative social status, as well as between abuse and positive and negative reciprocity. Social expectations and withdrawn behavior mediated between abuse and positive social status, but only where withdrawn behavior was a function of social expectations. Social expectations were generally found to mediate between abuse and internalizing problems. Negative social status (peer rejection) added to social expectations in producing internalizing problems. Identification of these mediating pathways can serve to guide secondary preventive intervention efforts so that they best address the problems abused children face in the absence of adequate parental and peer support as the children enter adolescence. PMID- 11771910 TI - Multiple maltreatment, attribution of blame, and adjustment among adolescents. AB - The study examined the predictive utility of blame attributions for maltreatment. Integrating theory and research on blame attribution, it was predicted that self blame would mediate or moderate internalizing problems, whereas other-blame would mediate or moderate externalizing problems. Mediator and moderator models were tested separately. Adolescents (N = 160, ages 11-17 years) were randomly selected from the open caseload of a child protection agency. Participants made global maltreatment severity ratings for each of physical abuse, psychological abuse, neglect. sexual abuse, and exposure to family violence. Participants also completed the Attribution for Maltreatment Interview (AFMI), a structured clinical interview that assessed self- and perpetrator blame for each type of maltreatment they experienced. The AFMI yielded five subscales: self-blaming cognition, self-blaming affect, self-excusing. perpetrator blame, and perpetrator excusing. Caretaker-reported (Child Behavior Checklist) and self-reported (Youth Self Report) internalizing and externalizing were the adjustment criteria. Controlling for maltreatment severity, the AFMI subscales explained significant variance in self-reported adjustment. Self-blaming affect was the most potent attribution, particularly among females. Attributions mediated maltreatment severity for self-reported adjustment but moderated it for caretaker-reported adjustment. The sophistication and relevance of blame attributions to adjustment are discussed, and implications for research and clinical practice are identified. PMID- 11771911 TI - Childhood maltreatment, posttraumatic stress symptomatology, and adolescent dating violence: considering the value of adolescent perceptions of abuse and a trauma mediational model. AB - The present study, utilizing both a child protective services and high school sample of midadolescents, examined the issue of self-report of maltreatment as it relates to issues of external validity (i.e., concordance with social worker ratings). reliability (i.e.. overlap with an alternate child maltreatment self report inventory; association of a self-labeling item as "abused" with their subscale item counterparts), and construct validity (i.e., the association of maltreatment with posttraumatic stress symptomatology and dating violence). Relevant theoretical work in attachment, trauma, and relationship violence points to a mediational model, whereby the relationship between childhood maltreatment and adolescent dating violence would be expected to be accounted for by posttraumatic stress symptomatology. In the high school sample, 1329 adolescents and, in the CPS sample, 224 youth on the active caseloads completed comparable questionnaires in the three domains of interest. For females only, results supported a mediational model in the prediction of dating violence in both samples. For males, child maltreatment and trauma symptomatology added unique contributions to predicting dating violence. with no consistent pattern emerging across samples. When considering the issue of self-labeling as abused. CPS females who self-labeled had higher posttraumatic stress symptomatology and dating violence victimization scores than did their nonlabeling, maltreated counterparts for emotional maltreatment. These results point to the need for ongoing work in understanding the process of disclosure and how maltreatment experiences are consciously conceptualized. PMID- 11771912 TI - Child maltreatment and the early onset of problem behaviors: can a program of nurse home visitation break the link? AB - This study investigated the relationship between child maltreatment and the early onset of problem behaviors in the Elmira Nurse Home Visitation Program. Participants were predominantly low-income and unmarried mothers and their first born children who were randomized either to receive over 2 years of home visitation services by nurses or to be placed in a comparison group. Data were drawn from a follow-up study that took place when the children were 15 years of age. Results demonstrated that, in the comparison group. child maltreatment was associated with significant increases in the number of early onset problem behaviors reported by the youth. For the youth in the nurse-visited group there was no relationship between maltreatment and early onset problem behaviors. We suggest that this finding was due to the effects of the intervention in reducing the number as well as the developmental timing of the maltreatment incidents. Results suggest that prenatal and infancy home visiting by nurses can moderate the risk of child maltreatment as a predictor of conduct problems and antisocial behavior among children and youth born into at-risk families. PMID- 11771914 TI - Pathways from child maltreatment to internalizing problems: perceptions of control as mediators and moderators. AB - Using a prospective longitudinal design, we examined internalizing problems and perceptions of control in a community sample of 785 children, 59 of whom had been maltreated. Children's internalizing problems and perceptions of control were measured via self-report at annual assessments in third grade through seventh grade (modal ages 9-13 years). Children's experiences of multiple types of maltreatment were rated based on social service records, using a standard coding system. Results of longitudinal analyses examining the roles of specific types of maltreatment (neglect, harsh parenting, and sexual abuse) revealed that neglect and sexual abuse were each associated with more internalizing problems, especially among children who experienced both these maltreatment types. Neglected children reported higher levels of perceived external control than other children did. Sexual abuse was associated with higher levels of perceived external control, but only among children who had also been neglected. Results of mediation analyses showed that higher levels of perceived external control accounted substantially for associations between specific maltreatment types and children's internalizing problems. Results of moderator analyses revealed that, among maltreated children, greater perceived internal control predicted fewer internalizing problems, suggesting that perceived internal control functioned as a protective factor. Children maltreated early in life were less likely to have this protective characteristic. Results are discussed in terms of their implications for understanding the developmental consequences of specific and co occurring types of maltreatment. PMID- 11771913 TI - The timing of child physical maltreatment: a cross-domain growth analysis of impact on adolescent externalizing and internalizing problems. AB - In a sample of 578 children assessed in kindergarten through the eighth grade, we used growth modeling to determine the basic developmental trajectories of mother reported and teacher-reported externalizing and internalizing behaviors for three physical maltreatment groups of children-early-harmed (prior to age 5 years), later-harmed (age 5 years and over), and nonharmed--controlling for SES and gender. Results demonstrated that the earlier children experienced harsh physical treatment by significant adults, the more likely they were to experience adjustment problems in early adolescence. Over multiple domains, early physical maltreatment was related to more negative sequelae than the same type of maltreatment occurring at later periods. In addition, the fitted growth models revealed that the early-harmed group exhibited someswhat higher initial levels of teacher-reported externalizing problems in kindergarten and significantly different rates of change in these problem behaviors than other children, as reported by mothers over the 9 years of this study. The early-harmed children were also seen by teachers, in kindergarten, as exhibiting higher levels of internalizing behaviors. The later-harmed children were seen by their teachers as increasing their externalizing problem behaviors more rapidly over the 9 years than did the early- or nonharmed children. These findings indicate that the timing of maltreatment is a salient factor in examining the developmental effects of physical harm. PMID- 11771915 TI - Maltreatment of boys and the development of disruptive and delinquent behavior. AB - Data from a longitudinal, inner-city community sample were used to examine the prevalence of child maltreatment in males and to relate this to disruptive and delinquent child behavior. By age 18 years, almost one fourth of the families had been referred to Children and Youth Services (CYS). Investigation by the CYS resulted in substantiated maltreatment of 10% of the participants, mostly for physical abuse and neglect. Almost all maltreatment was perpetrated by people living in the same house as the victim. Maltreatment was related to the boys progressing on three pathways in disruptive and delinquent behavior: authority conflict pathway, overt pathway, and covert pathway. Two thirds of the victims showed authority conflict problems, and almost all of the maltreated boys displayed behaviors characteristic of the overt and covert pathways. Victims, compared to matched controls, were more likely to have engaged in behaviors characteristic of the authority conflict and the overt pathways but less strongly engaged in behaviors associated with the covert pathway. Victims were also more likely than controls to have a referral to juvenile court. Most of the CYS contact tended to precede or co-occur with onset of overt and covert problem behavior, but about half of the onset of authority conflict behaviors tended to precede contact with CYS. PMID- 11771916 TI - The importance of timing: the varying impact of childhood and adolescent maltreatment on multiple problem outcomes. AB - A substantial body of literature suggests that childhood maltreatment is related to negative outcomes during adolescence, including delinquency, drug use, teenage pregnancy, and school failure. There has been relatively little research examining the impact that variation in the developmental stage during which the maltreatment occurs has on these relationships, however. In this paper, we reassess the impact of maltreatment on a number of adverse outcomes when developmentally specific measures of maltreatment-maltreatment that occurs only in childhood, only in adolescence, or in both childhood and adolescence-are considered. Data are drawn from the Rochester Youth Development Study, a broad based longitudinal study of adolescent development. The analysis examines how maltreatment affects delinquency, drug use, alcohol-related problems, depressive symptoms, teen pregnancy. school dropout, and internalizing and externalizing problems during adolescence. We also examine whether the type of maltreatment experienced at various developmental stages influences the outcomes. Overall, our results suggest that adolescent and persistent maltreatment have stronger and more consistent negative consequences during adolescence than does maltreatment experienced only in childhood. PMID- 11771917 TI - Child abuse and neglect and the development of mental disorders in the general population. AB - Child abuse and neglect have repeatedly been shown to be risks for psychiatric and personality disorders. However, much of this evidence is based on retrospective reports of adults. In addition, little is known about the developmental course of psychopathology among those exposed to child maltreatment. In this study, we report mental disorders assessed from early childhood to adulthood in those later identified as victims of abuse or neglect by official or self-report. Findings show elevated rates of mental disorders and symptoms in each of four groups relative to the normative sample. Groups included those who had been victims of physical abuse or neglect according to official report and those who had been victims of physical or sexual abuse by self-report. As expected, the maltreated groups were quite different demographically from the community comparison sample, especially those with official reports. The group with retrospective self-reports of physical abuse differed only modestly from the comparison group on the symptom and disorder measures, while the sexually abused group showed the most consistently elevated patterns, even after controls for demographic differences were taken into account. The disorder and symptom patterns differed both by group and by age: neglect cases showed a partial remission in adulthood, while official physical abuse cases showed an increasingly consolidated pattern of antisocial and impulsive behavior. PMID- 11771918 TI - Klinefelter syndrome and its variants: an update and review for the primary pediatrician. AB - Klinefelter syndrome is the most common chromosomal abnormality in humans. Recent prospective, unbiased studies have clarified many of the previous misconceptions associated with Klinefelter syndrome, thereby improving our recognition and management of this condition for affected individuals. The primary-care physician has an important role in caring for these individuals and their families by providing anticipatory guidance regarding issues relating to endocrinology, behavior, development, and preventive medical care. Furthermore, the primary-care giver can serve as a valuable source of support and advocacy for the family of a boy with Klinefelter syndrome. We review the current state of knowledge regarding Klinefelter syndrome and its variants, with an emphasis on medical and early developmental interventions. PMID- 11771919 TI - Restructuring an academic pediatric inpatient service using concepts developed by hospitalists. AB - In an effort to increase continuity of inpatient care by attending physicians, decrease use of hospital resources, and improve medical education without compromising quality of care, an inpatient pediatric ward service was restructured by using concepts developed by hospitalists. This reorganization reduced the number of yearly inpatient attendings, added a consistent 14-day call schedule, and eliminated attending outpatient responsibilities during their ward service. The restructured ward service attending acted as the attending of record for all general and specialty patients, excluding hematology/oncology, with the subspecialists fulfilling a consultant role. To evaluate the impact of this restructuring, a baseline year of the traditional ward service (TWS) was compared with a subsequent year of the restructured ward service (RWS). Our goal was to evaluate the impact of this new system on average costs of hospitalization, length of stay, resource utilization, inpatient mortality, and 7- and 31-day readmission rates. Hospital costs per patient were lower by 13% (p=0.018) in the restructured system. Average lengths of stay in an observation bed were significantly lower on the RWS (p=0.007), but there was no significant difference in admission length of stay. There was decreased resource utilization for laboratory and radiology tests (p<0.01) on the restructured service. Readmission rates were not significantly changed, and satisfaction among attendings, housestaff, students, and patients was uniformly high in both groups. A reorganized academic pediatric medical service, which allows specific attendings to focus on inpatient care and teaching, can decrease hospital resource utilization without compromising the quality of patient care or medical education. PMID- 11771921 TI - A neck mass in a young child. PMID- 11771920 TI - Use of propofol sedation in a pediatric emergency department: a prospective study. AB - The purpose of this study was to determine the efficacy and safety of propofol sedation for pediatric procedures in the emergency department. For patients needing painful procedures, propofol was administered intravenously. Vital signs, complications, and time to recovery were recorded. Patient amnesia and parent, patient, and operator satisfaction with sedation were assessed. The mean age was 7.4 years; 65% were male. Most underwent fracture reduction. Mean total dose was 3.3 mg/kg. Thirty percent experienced desaturation. One required assisted ventilation. Most had decreases in blood pressure. Mean recovery time was 18 minutes. Satisfaction with sedation was rated "excellent." Propofol was an effective sedation with minimal complications in the emergency department setting. PMID- 11771922 TI - Esophageal coins: are pennies different? PMID- 11771923 TI - Fluoxetine toxicity in a breastfed infant. PMID- 11771924 TI - Use of letters and phone calls to encourage preparticipation Special Olympics physical examinations to be done in a medical home: a randomized, controlled trial. PMID- 11771925 TI - Nitromusk compounds in women with gynecological and endocrine dysfunction. AB - Musk xylene (MX), musk ketone (MK), musk ambrette, musk moskene, and musk tibetene are synthetic fragrances. Between 1994 and 1996 these five nitromusk compounds (NMCs) were tested in the blood of 152 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. The testing was conducted by gas chromotography with mass-specific detector and mass spectrometry in a retrospective cross-sectional study. MX was detected in 95% and MK in 85% of the blood samples (>20 ng per liter whole blood). The median concentration of MX was 65.5 ng/L and the maximum level of MX was 1183 ng/L; the corresponding values for MK were respectively 55.5 and 518 ng/L. The other three NMCs were found in only a few patients or not at all. Significant associations between MX and MK concentrations were found in blood and different clinical parameters of the endocrine system. MX and MK may act centrally as a disrupter of the (supra-) hypothalamic-ovarian axis, which may result in a mild ovarian insufficiency. On the basis of our data, a reproductive toxicity and an endocrine effect of NMCs in women cannot be ruled out. Further experimental and clinical studies should be conducted. PMID- 11771926 TI - Breast-feeding and serum p,p'DDT levels among Mexican women of childbearing age: a pilot study. AB - For almost 50 years, millions of Mexicans have been directly and/or indirectly exposed to (1,1,1-trichloro-2,2-bis[p-chlorophenyl]ethane) (p,p'DDT). The potential related health outcomes of this exposure are of international concern. The objective of the study was to determine the effect of breast-feeding on serum levels of 1,1-dichloro-2; 2'-bis(p-chlorophenyl)ethylene (p,p'DDE) and p,p'DDT in women of childbearing age who were residents of the state of Morelos, Mexico. In March 1999, we examined a sample of 24 women, ages 21 to 36 years, who came with their children to the outpatient facility of a county Health Center in the state of Morelos. The geometric mean for p,p'DDE was 21.8 ng/ml+/-2.58 (GSD) and 2.9 ng/ml+/-2.84 for p,p'DDT. For each month of breast-feeding we observed similar significant decreases for both p,p'DDE (beta=-0.0403 per log concentration unit, P=0.001) and p,p'DDT (beta=-0.0309, P=0.03) serum levels, adjusted by mothers' age and number of children. The adjusted half-life estimate for p,p'DDE serum levels was 17 months. It was concluded that breast-feeding leads to rapid removal of p,p'DDT from the body (<2 year half-life) compared to nonlactational elimination rates (<5 year half-life). In this population, serum p,p'DDE levels were similar to those found 20 years ago in the United States. PMID- 11771927 TI - Enamel lead biomarker for prenatal exposure assessment. AB - The development of the enamel biomarker for heavy metal exposure assessment is designed to improve studies of dose-effect relationships to embryonic anomalies, particularly neurotoxic dysfunction. This report documents initial demonstrations of ambient lead (Pb) relative to calcium (Ca) in histological cross sections of deciduous tooth enamel of three human subjects, by use of ion mass spectrometry. The goal of this research was to measure Pb and Ca in tooth enamel for use as a temporal biomarker in assessing prenatal and postnatal exposure. This involves measurement of these heavy metals in enamel at high spatial resolution along histological transects following the temporal pattern of enamel growth. The technique may be applied when completely developed to cross-sectional and longitudinal research. PMID- 11771928 TI - Dental amalgam and selenium in blood. AB - It has been suggested that selenium (Se) exhibits protective effects against mercury (Hg) toxicity in humans due to formation of a Hg-Se complex bound to selenoprotein P in blood. The aim of the present study was to investigate Se concentrations in persons who had been examined with respect to general health problems associated with dental amalgam fillings. The Se concentrations were determined in whole-blood samples of 80 individuals by hydride generation atomic absorption spectrometry. The subjects comprised two main groups: 21 healthy controls with amalgam fillings and 20 patients who claimed symptoms from existing amalgam fillings. The median concentration of Se in blood (119.2 microg/L) was statistically significantly lower in subjects who claimed symptoms of mercury amalgam illness than in healthy subjects with amalgam (130.3 microg/L). The difference was more evident in individuals with more than 35 amalgam surfaces (P=0.003). Additional control groups without amalgam fillings comprised 19 healthy controls without amalgam experience and 20 subjects who have had amalgam fillings removed due to suspected symptoms associated with amalgam. The Se concentrations in these groups were not different from those with amalgam. It is indicated that persons with ill health self-related to dental amalgam might have a Se metabolism different from that of healthy people. PMID- 11771929 TI - Determinants of cadmium burden levels in a population of children living in the vicinity of nonferrous smelters. AB - This report covers part of the assessment of a site in northern France polluted by industrial metal emissions. Our objectives were to assess the cadmium burden in children aged 8 to 11 years and look for factors that affected it. A cross sectional population-based study took place in 1996-1997 and included 400 children (200 in the metal-polluted area). The geometric mean of the blood cadmium (CdB) levels of children living on the polluted site was 0.51 microg/L (95% CI=[0.49-0.53]); that of the nonexposed children was 0.47 microg/L (95% CI=[0.45-0.49]) (P<0.01). The geometric mean of the urinary cadmium (CdU) levels of children living on the polluted site was 1.16 microg/g creatinine (95% CI=[1.01-1.34]); that of the nonexposed children was 0.99 microg/g creatinine (95% CI=[0.86-1.14]) (P=0.10). Mean CdB was higher among children within 4 km of a zinc smelter and consuming > or =500 ml of tap water daily (x1.34; 95% CI=[1.14 1.51]) compared with children living more than 4 km away and consuming <500 ml of tap water daily. Independently of this association, consumption of fish and shellfish (> or =once a week vs. or =once daily vs. 0.35 in each case). These data make it unlikely that CV infections during pregnancy or in early childhood play a major role in the induction of islet autoimmunity in offspring of mothers or fathers with T1D or of mothers with gestational diabetes. PMID- 11771959 TI - Elevated levels of the 90 kDa heat shock protein (hsp90) in SLE correlate with levels of IL-6 and autoantibodies to hsp90. AB - Levels of the 90 kDa heat shock protein (hsp90) are elevated in a subset of patients with systemic lupus erythematosus (SLE) due to enhanced transcription of the hsp90beta gene. In cultured cells, transcription of the hsp90beta gene is induced following exposure to IL-6 or IL-10 which are known to be elevated in SLE patients. Here we have measured the levels of hsp90 protein and of IL-6, IL-10 in SLE patients and normal controls. We demonstrate that the levels of hsp90 protein in individual patients correlate with the IL-6 level but not with the level of IL 10. Moreover, hsp90 protein levels in patients correlate with the presence of IgG autoantibodies to hsp90. These results support a model in which elevated levels of IL-6 in SLE patients induce elevated levels of hsp90 protein which in turn results in the production of autoantibodies to this protein. PMID- 11771960 TI - Reactivities to the Sm autoantigenic complex and the synthetic SmD1-aa83-119 peptide in systemic lupus erythematosus and other autoimmune diseases. AB - The Sm antigenic complex is, besides dsDNA, the most important and specific autoimmune target in systemic lupus erythematosus (SLE). The population of anti Sm Ab elicited is very heterogeneous in terms of epitope specificity resulting in a strong assay dependent detectability. Based on the description of a new autoantigenic target, the SmD1-aa83-119 peptide, we analysed 50 healthy persons and 205 patients with different autoimmune and other disorders with regard to their anti-Sm reactivities using different assays. The prevalence of anti-SmD1 peptide Ab and anti-Sm Ab in SLE was 36.0 (40/111) and 9.9% (11/111), respectively. The respective values obtained for non-SLE patients were 2.8 (4/144) and 5.3% (5/94). In SLE, anti-SmD1 peptide Ab are positively correlated to disease activity, nephritis and anti-dsDNA Ab. The association between reactivities of SLE samples in the traditional anti-Sm and the anti-SmD1 peptide ELISA was found to be 63.6%, contrasting markedly with the situation in non-SLE patients (no double-positive sera). SLE samples with an anti-Sm response restricted to the SmD1 peptide are completely negative in immunoblot, supporting the conformational nature of this epitope. Positive immunoblot reactions with the SmD1 polypeptide are not inhabitable by the synthetic SmD1-aa83-119 peptide. Comparing anti-Sm reactivities detected by ELISAs with those in immunoblot, different patterns were observed, reflecting the heterogeneous autoimmune response to this antigen. In conclusion, the anti-SmD1-aa83-119 peptide ELISA substantially completes the panel of methods for autoantibody testing. As none of the assays presently available covers the whole spectrum of epitope specificities of anti-Sm Abs elicited in SLE, it does not replace traditional anti-Sm ELISAs. PMID- 11771962 TI - High level production of functional antibody Fab fragments in an oxidizing bacterial cytoplasm. AB - The antigen-binding fragments (Fab) of antibodies are powerful tools in clinical therapy, molecular diagnostics and basic research. However, their principal applications require pure recombinant molecules in large amounts, which are challenging to obtain. Severe limitations in yield, folding and functionality are commonly encountered in bacterial production of Fab fragments. Secretion into the oxidizing periplasm generally results in low yield, whereas expression in the reducing cytoplasmic environment produces unfolded or non-functional protein. We hypothesized that an impaired reducing environment of the cytoplasm would permit correctly folded, functional cytoplasmic expression of Fabs with high yield. We used the Escherichia coli strain FA113, which has no activity of both thioredoxin and glutathione reductase, and thus has an oxidizing cytoplasmic environment. With the newly constructed vector pFAB1 we tested the cytoplasmic expression of two Fab fragments, which recognize the integral membrane protein NhaA, a bacterial Na(+)/H(+) antiporter. These antibodies differ in terms of DNA sequence and stability. Both antibody fragments were produced to very high yields (10-30 mg/l from bacterial cultures at an A(600 nm)=1.2-1.3). This is a factor 50-250 times higher than any other reported over-expression strategy for Fab fragments and currently represents the highest production rate ever been reported for antibody Fab fragments in bacteria grown to similar cell densities. The fragments are fully functional and can be efficiently purified by His-tag chromatography. Expression of active Fab fragments in the bacterial cytoplasm unlocks the possibility of using antibody specific targeting in an intracellular environment. Such a capacity opens new perspectives for investigating metabolic and regulatory pathways in vivo and also provides a powerful selection system for functional genomics. PMID- 11771963 TI - The three-dimensional structure of a vertebrate wide (slow muscle) Z-band: lessons on Z-band assembly. AB - The vertebrate muscle Z-band organizes and tethers antiparallel actin filaments in adjacent sarcomeres and hence propagates the tension generated by the actomyosin interaction during muscular contraction. The axial width of the Z-band varies with fibre and muscle type: fast twitch muscles have narrow (approximately 30-50 nm) Z-bands, while slow-twitch and cardiac muscles have wide (approximately 100-140 nm) Z-bands. In electron micrographs of longitudinal sections of fast fibres like those found in fish body white muscle, the Z-band appears as a characteristic zigzag layer of density connecting the mutually offset actin filament arrays in adjacent sarcomeres. Wide Z-bands in slow fibres such as the one studied here (bovine neck muscle) show a stack of three or four zigzag layers. The variable Z-band width incorporating variable numbers of zigzag layers presumably relates to the different mechanical properties of the respective muscles. Three-dimensional reconstructions of Z-bands reveal that individual zigzag layers are often composed of more than one set of protein bridges, called Z-links, probably alpha-actinin, between oppositely oriented actin filaments. Fast muscle Z-bands comprise two or three layers of Z-links. Here we have applied Fourier reconstruction methods to obtain clear three-dimensional density maps of the Z-bands in beef muscle. The bovine slow muscle investigated here reveals a Z band comprising six sets of Z-links, which, due to their shape and the way their projected densities overlap, appear in longitudinal sections as either three or four zigzag layers, depending on the lattice view. There has been great interest recently in the suggestion that Z-band variability with fibre type may be due to differences in the repetitive region (tandem Z-repeats) in the Z-band part of titin (also called connectin). We discuss this in the context of our results and present a systematic classification of Z-band types according to the numbers of Z links and titin Z-repeats. PMID- 11771964 TI - Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility. AB - The flexibility of different regions of HIV-1 protease was examined by using a database consisting of 73 X-ray structures that differ in terms of sequence, ligands or both. The root-mean-square differences of the backbone for the set of structures were shown to have the same variation with residue number as those obtained from molecular dynamics simulations, normal mode analyses and X-ray B factors. This supports the idea that observed structural changes provide a measure of the inherent flexibility of the protein, although specific interactions between the protease and the ligand play a secondary role. The results suggest that the potential energy surface of the HIV-1 protease is characterized by many local minima with small energetic differences, some of which are sampled by the different X-ray structures of the HIV-1 protease complexes. Interdomain correlated motions were calculated from the structural fluctuations and the results were also in agreement with molecular dynamics simulations and normal mode analyses. Implications of the results for the drug resistance engendered by mutations are discussed briefly. PMID- 11771965 TI - Helices VII and X in the lactose permease of Escherichia coli: proximity and ligand-induced distance changes. AB - By using functional lactose permease devoid of native Cys residues with a discontinuity in the periplasmic loop between helices VII and VIII (N(7)/C(5) split permease), cross-linking between engineered paired Cys residues in helices VII and X was studied with the homobifunctional, thiol-specific cross-linkers 1,1 methanediyl bismethanethiosulfonate (3 A), N,N'-o- phenylenedimaleimide (6 A) and N,N'-p-phenylenedimaleimide (10 A). Mutant Asp240-->Cys (helix VII)/Lys319-->Cys (helix X) cross-links most efficiently with the 3 A reagent, providing direct support for studies indicating that Asp240 and Lys319 are in close proximity and charge paired. Furthermore, cross-linking the two positions inactivates the protein. Other Cys residues more disposed towards the middle of helix VII cross link to Cys residues in the approximate middle of helix X, while no cross-linking is evident with paired Cys residues at the periplasmic or cytoplasmic ends of these helices. Thus, helices VII and X are in close proximity in the middle of the membrane. In the presence of ligand, the distance between Cys residues at positions 240 (helice VII) and 319 (helix X) increases. In contrast, the distance between paired Cys residues more disposed towards the cytoplasmic face of the membrane decreases in a manner suggesting that ligand binding induces a scissors like movement between the two helices. The results are consistent with a recently proposed mechanism for lactose/H(+) symport in which substrate binding induces a conformational change between helices VII and X, during transfer of H(+) from His322 (helix X)/Glu269 (helix VIII) to Glu325 (helix X). PMID- 11771966 TI - Transmembrane domain mediated self-assembly of major coat protein subunits from Ff bacteriophage. AB - The 50-residue major coat protein (MCP) of Ff bacteriophage exists as a single spanning membrane protein in the Escherichia coli host inner membrane prior to assembly into lipid-free virions. Here, the molecular bases for the specificity and stoichiometry that govern the protein-protein interactions of MCP in the host membrane are investigated in detergent micelles. To address these structural issues, as well as to circumvent viability requirements in mutants of the intact protein, peptides corresponding to the effective alpha-helical TM segment of wild type and mutant bacteriophage MCPs were synthesized. Fluorescence resonance energy transfer (FRET) experiments on the dansyl and dabcyl-labeled MCP TM domain peptides in detergent micelles demonstrated that the peptides specifically associate into non-covalent homodimers, as postulated for the biologically relevant membrane-embedded MCP oligomer. MCP peptides labeled with short-range pyrene fluorophores at the N terminus displayed excimer fluorescence consistent with homodimerization occurring in a parallel fashion. Variant peptides synthesized with single substitutions at helix-interactive positions displayed a wide range of dimer/monomer ratios on SDS-PAGE gels, which are interpreted in terms of steric volume, presence or absence of beta-branching, and the effect of polar substituents. The overall results indicate discrete roles for helix-helix interfacial residues as packing recognition elements in the membrane-inserted state, and suggest a possible correlation between phage viability and efficacy of MCP TM-TM interactions. PMID- 11771967 TI - Archaeal group II chaperonin mediates protein folding in the cis-cavity without a detachable GroES-like co-chaperonin. AB - Group II chaperonins of archaea and eukaryotes are distinct from group I chaperonins of bacteria. Whereas group I chaperonins require the co-chaperonin Cpn-10 or GroES for protein folding, no co-chaperonin has been known for group II. The protein folding mechanism of group II chaperonins is not yet clear. To understand this mechanism, we examined protein refolding by the recombinant alpha or beta-subunit chaperonin homo-oligomer (alpha16mer and beta16mer) from a hyperthermoplilic archaeum, Thermococcus strain KS-1, using a model substrate, green fluorescent protein (GFP). The alpha16mer and beta16mer captured the non native GFP and promoted its refolding without any co-chaperonin in an ATP dependent manner. A non-hydrolyzable ATP analog, AMP-PNP, induced the GFP refolding mediated by beta16mer but not by the alpha16mer. A mutant alpha-subunit chaperonin homo-oligomer (trap-alpha) could capture the non-native protein but lacked the ability to refold it. Although trap-alpha suppressed ATP-dependent refolding of GFP mediated by alpha16mer or beta16mer, it did not affect the AMP PNP-dependent refolding. This indicated that the GFP refolding mediated by beta16mer with AMP-PNP was not accessible to the trap-alpha. Gel filtration chromatography and a protease protection experiment revealed that this refolded GFP, in the presence of AMP-PNP, was associated with beta16mer. After the completion of GFP refolding mediated by beta16mer with AMP-PNP, addition of ATP induced an additional refolding of GFP. Furthermore, the beta16mer preincubated with AMP-PNP showed the ability to capture the non-native GFP. These suggest that AMP-PNP induced one of two chaperonin rings (cis-ring) to close and induced protein refolding in this ring, and that the other ring (trans-ring) could capture the unfolded GFP which was refolded by adding ATP. The present data indicate that, in the group II chaperonin of Thermococcus strain KS-1, the protein folding proceeds in its cis-ring in an ATP-dependent fashion without any co-chaperonin. PMID- 11771969 TI - A general statistical analysis for fMRI data. AB - We propose a method for the statistical analysis of fMRI data that seeks a compromise between efficiency, generality, validity, simplicity, and execution speed. The main differences between this analysis and previous ones are: a simple bias reduction and regularization for voxel-wise autoregressive model parameters; the combination of effects and their estimated standard deviations across different runs/sessions/subjects via a hierarchical random effects analysis using the EM algorithm; overcoming the problem of a small number of runs/session/subjects using a regularized variance ratio to increase the degrees of freedom. PMID- 11771970 TI - Visual feature and conjunction searches of equal difficulty engage only partially overlapping frontoparietal networks. AB - According to a classical view of visual object recognition, targets are detected "pre-attentively" if they carry unique features, whereas attention has to be deployed serially to object locations for feature binding if the targets can be distinguished from distracters only in terms of their feature conjunctions. Consistent with this view, recent reports suggest a contribution of the posterior parietal cortex (PPC; one major region controlling spatial attention) to conjunction search as opposed to feature search. However, PPC engagement in conjunction search might also reflect feature-based attention or the difficulty of target selection. The present fMRI study compared regions and amplitudes of cortical activity reflecting the attention mechanisms of a conjunction and a feature search of equal difficulty performed during maintenance of fixation. Attention-related activity was assessed by comparing each hard feature and conjunction search with an easy feature search. Hard feature and conjunction search activated overlapping regions in multiple PPC areas and in the frontal eye field (FEF). Most consistent PPC overlaps were located in the anterior and posterior intraparietal sulcus (IPS). The response amplitude of posterior IPS did not differ between both search tasks. However, the IPS junction with the transverse occipital sulcus and the FEF responded at a higher amplitude during conjunction search. Moreover, regions of the prefrontal cortex and the PPC were activated only during either hard feature or conjunction search. These findings suggest that equally difficult visual searches for features and conjunctions are controlled by overlapping frontoparietal networks, but also that both search types involve specific mechanisms. PMID- 11771971 TI - A single dose of the serotonin neurotransmission agonist paroxetine enhances motor output: double-blind, placebo-controlled, fMRI study in healthy subjects. AB - Since serotonin (5-HT) stimulates motor function, pharmacological potentiation of 5-HT neurotransmission may improve motor function in healthy subjects and, possibly, recovery in post-stroke patients. Indeed, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increased activation in executive motor areas of healthy subjects as fenozolone, a releaser of monoamines (including noradrenaline, dopamine, and serotonin) from intracellular stores. This study is intended to test the hypothesis that paroxetine can likewise modulate brain motor activity in a dose-dependent manner in healthy subjects. In a double-blind counterbalanced study, six subjects underwent functional MRI examinations on three sessions 1 week apart (E1, E2, and E3) at the time of peak plasma concentrations (5 h after drug intake, i.e., either 20 or 60 mg of paroxetine or placebo) with a complex sequential opposition task. Rest and activation alternated in a block design. During activation, subjects performed, with the right hand, a 1-Hz-paced task that alternated two fist closings with a sequential opposition task. Paroxetine elicited effects similar to those reported for fluoxetine; notable changes were hyperactivation in the contralateral S1/M1, and posterior SMA and widespread hypoactivation of basal ganglia and cerebellum. There was an inverse correlation between dose and effect: significantly greater effects were observed with the 20-mg dose compared with 60 mg. Paroxetine dose dependently modulates activation of the entire motor pathway in a way that favors motor output. Thus, a single dose of the SSRI paroxetine reorganized motor processing. PMID- 11771972 TI - On the use of caffeine as a contrast booster for BOLD fMRI studies. AB - This study explored the possible use of caffeine as an agent to improve the BOLD (blood oxygen level-dependent) signal response in fMRI. Previous research has demonstrated that caffeine has the ability to reset the level of coupling between blood flow and neuronal activity. In the present study, it has been shown that caffeine causes a decrease in cerebral perfusion by as much as 13.2% without a change in performance. Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4.4%. During activation, the vasculature responds from below-normal baseline levels with a normal increase in blood flow and volume, resulting in an overall increase in the BOLD contrast. This increase can be as large as 22-37% during the performance of a visually cued motor task. The benefit of such a large increase in the BOLD contrast could be used to improve the image resolution, the acquisition scheme, or the task design of fMRI experiments. Caffeine has the potential to be used as a contrast booster for fMRI experiments. PMID- 11771973 TI - Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing. AB - Positron emission tomography was used to investigate common versus specific cortical regions for the maintenance of spatial versus phonological information in working memory (WM). Group and single-subject analyses of regional cerebral blood flow during a new 2 x 2 factorial n-back task were performed. Eight subjects had to memorize either phonological features or the location of serially presented syllables. Brain activation during phonological judgment and spatial judgment (0-back) was compared with that during two corresponding WM conditions (2-back). We observed a common network associated with the requirement of maintaining and sequencing items in WM. Seven or more subjects activated (posterior) superior frontal sulcus (pSFS, BA 6/8, global maximum) and/or adjacent gyri, posterior parietal cortex, and precuneus (BA 7). Less consistently, bilateral middle frontal gyrus (BA 9/46) was involved. Bilateral anterior (BA 39/40) and posterior (BA 7) intraparietal sulcus, as well as right pSFS, exhibited dominance for spatial WM. Although underlying stimulus processing pathways for both types of information were different, no region specific for phonological WM was found. Robust activation within the left inferior frontal gyrus (BA 44 and 45) was present, during both phonological WM and phonological judgment. We conclude that the controversial left prefrontal lateralization for verbal WM reflects more general phonological processing strategies, not necessarily required by tasks using letters. We propose a stimulus-independent role for the bilateral pSFS and its vicinity for maintenance and manipulation of different context-dependent information within working memory. PMID- 11771974 TI - Simulating transcranial magnetic stimulation during PET with a large-scale neural network model of the prefrontal cortex and the visual system. AB - Transcranial magnetic stimulation (TMS) exerts both excitatory and inhibitory effects on the stimulated neural tissue, although little is known about the neurobiological mechanisms by which it influences neuronal function. TMS has been used in conjunction with PET to examine interregional connectivity of human cerebral cortex. To help understand how TMS affects neuronal function, and how these effects are manifested during functional brain imaging, we simulated the effects of TMS on a large-scale neurobiologically realistic computational model consisting of multiple, interconnected regions that performs a visual delayed match-to-sample task. The simulated electrical activities in each region of the model are similar to those found in single-cell monkey data, and the simulated integrated summed synaptic activities match regional cerebral blood flow (rCBF) data obtained in human PET studies. In the present simulations, the excitatory and inhibitory effects of TMS on both locally stimulated and distal sites were studied using simulated behavioral measures and simulated PET rCBF results. The application of TMS to either excitatory or inhibitory units of the model, or both, resulted in an increased number of errors in the task performed by the model. In experimental studies, both increases and decreases in rCBF following TMS have been observed. In the model, increasing TMS intensity caused an increase in rCBF when TMS exerted a predominantly excitatory effect, whereas decreased rCBF following TMS occurred if TMS exerted a predominantly inhibitory effect. We also found that regions both directly and indirectly connected to the stimulating site were affected by TMS. PMID- 11771975 TI - Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation. AB - In the present studies fMRI and a hypercapnic calibration procedure were used to monitor simultaneous changes in cerebral blood flow (CBF), cerebral blood oxygenation, and cerebral metabolic rate of oxygen (CMRO(2)) during activation in the sensorimotor cortex. In the first set of experiments seven volunteers performed bilateral, self-paced finger tapping and in the second set of experiments six volunteers performed bilateral finger tapping with six different frequencies (0.5-3 Hz). During the latter task relative CBF and BOLD signal intensity changes varied linearly as a function of stimulus frequency. In good agreement with recent PET and fMRI data increases in CMRO(2) were smaller than the corresponding changes in CBF during self-paced finger tapping and at all levels of graded motor activation. At a single level of activation and during graded activation there was a positive linear relationship between CBF and CMRO(2) with ratios of approximately 3:1. Comparable proportionality constants have been found in the visual cortex and primary sensory cortex, indicating similarities between the relationship of CBF and CMRO(2) in various cortical regions. PMID- 11771976 TI - Detecting latency differences in event-related BOLD responses: application to words versus nonwords and initial versus repeated face presentations. AB - We introduce a new method for detecting differences in the latency of blood oxygenation level-dependent (BOLD) responses to brief events within the context of the General Linear Model. Using a first-order Taylor approximation in terms of the temporal derivative of a canonical hemodynamic response function, statistical parametric maps of differential latencies were estimated via the ratio of derivative to canonical parameter estimates. This method was applied to two example datasets: comparison of words versus nonwords in a lexical decision task and initial versus repeated presentations of faces in a fame-judgment task. Tests across subjects revealed both magnitude and latency differences within several brain regions. This approach offers a computationally efficient means of detecting BOLD latency differences over the whole brain. Precise characterization of the hemodynamic latency and its interpretation in terms of underlying neural differences remain problematic, however. PMID- 11771977 TI - Negative dip in BOLD fMRI is caused by blood flow--oxygen consumption uncoupling in humans. AB - The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect. PMID- 11771978 TI - CSF spaces of the Sylvian fissure region in severe melancholic depression. AB - The Sylvian fissure region gathers lateral frontotemporal cortices and subcortical structures that are frequently disturbed in patients with mood disorders. We have investigated possible CSF space changes in this brain region in severe melancholic depression. Fifty-seven patients and 37 control subjects received three-dimensional MRI. CSF volumes were obtained for cerebral CSF, lateral ventricles, and both Sylvian fissure regions. As a group, patients showed a significant CSF space enlargement that was prominent around the Sylvian fissure, particularly in the left hemisphere. Likewise, evident leftward asymmetry was more frequent in the patient group (patients 31.6%, controls 2.7%). The combination of CSF space enlargement and the pattern of Sylvian CSF asymmetry predicted the patient condition with 62.2% specificity and 82.5% sensitivity. We conclude that, in the context of a broad severity spectrum of imaging alterations in severe melancholic depression, asymmetrical CSF space enlargement may be evident in the Sylvian fissure region. PMID- 11771979 TI - Laser Doppler flowmetry mapping of cerebrocortical microflow: characteristics and limitations. AB - The aim of this study was to quantitatively analyze the amount of methodological noise and the spatial and temporal variability of laser Doppler flowmetry (LDF) signals mapping cerebrocortical microflow. In an experimental setup with latex beads, the methodological LDF-signal variability was determined (coefficient of variation or CV(method)). The biological variability of the LDF signals was measured in animal experiments using 10 anesthetized rabbits. One stationary reference probe was used to assess temporal heterogeneity (CV(temp)) and a micromanipulator-driven scanning probe was used to assess spatial heterogeneity (CV(spat)) in a cortical area of 3.5 x 4.5 mm with 252 measurement points. CO(2) tests were used to modulate cerebrovascular resistance. CV(method) was found to be 4.94 +/- 1.7. The CV(temp) for the LDF-velocity signal was assessed to be 13.93 +/- 5.9 during normocapnia. Scanning of the brain surface with the scanning probe revealed a CV(spat) for LDF velocity of 65.0 +/- 16.2 during normocapnia. CO(2) modulation (hypocapnia --> normocapnia --> hypercapnia) of the cerebral resistance did not show a significant change in temporal heterogeneity (10.84 +/- 3.1 --> 13.93 +/- 5.9 --> 14.82 +/- 3.9), whereas spatial heterogeneity decreased significantly (81.31 +/- 12.0 --> 65.0 +/- 16.2 --> 54.04 +/- 21.8). Although the spatial and temporal variability of LDF signals evoked by cerebrocortical microflow is in the same range as with other methods and in other organs, LDF cerebrocortical mapping is restricted by the large temporal and spatial heterogeneity of the cerebrocortical vasculature. The definitions of sample volume, scanning step width, probe to brain surface distance, and average time per scanning point are critical concerning reliable LDF cerebrocortical mapping techniques. PMID- 11771980 TI - Compensation of susceptibility-induced BOLD sensitivity losses in echo-planar fMRI imaging. AB - Gradient-echo echo-planar imaging is a standard technique in functional magnetic resonance imaging (fMRI) experiments based on the blood oxygenation level dependent (BOLD) effect. A major problem is the occurrence of susceptibility gradients near air/tissue interfaces. As a consequence, the detection of neuronal activation may be greatly compromised in certain brain areas, especially in the temporal lobes and in the orbitofrontal cortex. Common approaches to overcome this problem, such as z-shimming or the use of tailored radio frequency pulses, usually compensate only for susceptibility gradients in the slice selection direction. In the present study, the influence of susceptibility gradients in the phase encoding direction is investigated both theoretically and experimentally. It is shown that these gradients influence the effective echo time TE and may reduce considerably the local BOLD sensitivity, even in the case of acceptable image intensities. A compensation method is proposed and tested in an fMRI experiment based on a hypercapnic challenge. The results suggest that the compensation method allows for the detection of activation in brain areas which are usually unavailable for BOLD studies. PMID- 11771981 TI - Echo time dependence of BOLD contrast and susceptibility artifacts. AB - Echo-planar imaging with gradient echo allows whole-brain images to be rapidly acquired. However, its main limitation is that magnetic field inhomogeneities in regions of the brain close to bone and air-filled sinuses result in reduced signal-to-noise ratio and signal loss. In particular this is a problem for imaging the temporal lobes, and can therefore affect the results of some language related studies. Decreasing the echo time (TE) increases the signal-to-noise ratio and reduces the amount of signal loss in susceptible regions. In this study we investigate the TE dependence of BOLD (blood oxygenation level-dependent) contrast and, in particular, how it is influenced in regions with susceptibility artifacts. We use a dual echo-time sequence to compare brain activations measured with two different TEs, TE = 40 ms and TE = 27 ms. The paradigm involves comparing famous faces to scrambled faces, a low-level control condition. It was chosen because famous faces have been repeatedly shown to activate the fusiform gyri and anterior temporal lobes in both PET and fMRI. Our results show that it is possible to detect robust activations at a lower TE in brain regions not affected by susceptibility artifacts (i.e., fusiform gyri), allowing for faster scanning times. However, although the amount of signal loss is reduced at the lower TE, this does not appear to be sufficient to recover the BOLD signal in regions affected by susceptibility artifacts (i.e., anterior temporal lobes). PMID- 11771982 TI - The role of action knowledge in the comprehension of artefacts--a PET study. AB - Activation of the left ventral premotor cortex (PMv) has in previous imaging studies been associated with the processing of visually presented artefacts. It has been suggested that this activation reflects processing of action knowledge and that action knowledge contributes to the comprehension of artefacts. The purpose of the present study was to test whether activation of the left PMv is common for all tasks involving the comprehension of artefacts or whether it is task specific. This was done by comparing performance and regional cerebral blood flow (rCBF) associated with two categorization tasks and two naming tasks divided by category (natural objects vs artefacts). The left PMv (BA 6/44) was more activated by the categorization task for artefacts than by the categorization task for natural objects and the naming task for artefacts. However, the left PMv was not associated with the contrast between the naming task for artefacts and the naming task for natural objects nor with the processing of artefacts in general. If the PMv does mediate action knowledge, these results suggest that action knowledge does not contribute directly to the comprehension of artefacts but may support the categorization of artefacts. The significance of these findings is discussed in relation to category-specific recognition impairments for artefacts. PMID- 11771983 TI - Aging and cholinergic modulation of the transient magnetic 40-Hz auditory response. AB - Cholinergic blockade by scopolamine, a central muscarinic receptor antagonist, may produce transient memory impairment in healthy subjects, and it has been used as a neurochemical model of cognitive degeneration in aged individuals. To observe the muscarinic modulation of memory and cortical auditory processing, nine cognitively intact elderly subjects (59-80 years) were studied using neuropsychological tests and 122-channel magnetoencephalography (MEG) after an administration of scopolamine hydrobromide (0.3 mg, i.v.) or glycopyrrolate (0.2 mg, i.v.), a peripheral muscarinic antagonist. A double-blind randomized crossover design was used in two sessions separated by at least 1 week. Scopolamine, but not glycopyrrolate, produced a transient impairment of verbal memory performance in the elderly subjects. MEG indicated that the auditory evoked 40-Hz magnetic response was significantly larger after scopolamine than after glycopyrrolate administration. Furthermore, reanalysis of our earlier results in younger subjects (20-31 years), basically supporting the present MEG findings, tentatively suggests that the scopolamine effects on the 40-Hz response may be slightly pronounced with aging. In sum, the transient magnetic 40-Hz auditory response may be useful in studies on brain cholinergic deficits in elderly subjects. PMID- 11771984 TI - The influence of brain tissue anisotropy on human EEG and MEG. AB - The influence of gray and white matter tissue anisotropy on the human electroencephalogram (EEG) and magnetoencephalogram (MEG) was examined with a high resolution finite element model of the head of an adult male subject. The conductivity tensor data for gray and white matter were estimated from magnetic resonance diffusion tensor imaging. Simulations were carried out with single dipoles or small extended sources in the cortical gray matter. The inclusion of anisotropic volume conduction in the brain was found to have a minor influence on the topology of EEG and MEG (and hence source localization). We found a major influence on the amplitude of EEG and MEG (and hence source strength estimation) due to the change in conductivity and the inclusion of anisotropy. We expect that inclusion of tissue anisotropy information will improve source estimation procedures. PMID- 11771985 TI - Differential contribution of frontal and temporal cortices to auditory change detection: fMRI and ERP results. AB - The present study addresses the functional role of the temporal and frontal lobes in auditory change detection. Prior event-related potential (ERP) research suggested that the mismatch negativity (MMN) reflects the involvement of a temporofrontal network subserving auditory change detection processes and the initiation of an involuntary attention switch. In the present study participants were presented with repetitive spectrally rich sounds. Infrequent changes of either small (10% change), medium (30% change), or large (100% change) magnitude were embedded in the stimulus train. ERPs and fMRI measures were obtained in the same subjects in subsequent sessions. Significant hemodynamic activation in the superior temporal gyri (STG) bilaterally and the opercular part of the right inferior frontal gyrus was observed for large and medium deviants only. ERPs showed that small deviants elicited MMN when presented in silence but not when presented with recorded MR background noise, indicating that small deviants were hardly detected under fMRI conditions. The MR signal change in temporal lobe regions was larger for large than for medium deviants. For the right fronto opercular cortex the opposite pattern was observed. The strength of the temporal activation correlated with the amplitude of the change-related ERP at around 110 ms from stimulus onset while the frontal activation correlated with the change related ERP at around 150 ms. These results suggest that the right fronto opercular cortex is part of the neural network generating the MMN. Three alternative explanations of these findings are discussed. PMID- 11771986 TI - Iterative versus filtered backprojection reconstruction for statistical parametric mapping of PET activation measurements: a comparative case study. AB - The significance of task-induced cerebral blood flow responses, assessed using statistical parametric mapping, depends, among other things, on the signal-to noise ratio (SNR) of these responses. Generally, positron emission tomography sinograms of H(2)(15)O activation studies are reconstructed using filtered backprojection (FBP). Alternatively, the acquired data can be reconstructed using an iterative reconstruction procedure. It has been demonstrated that the application of iterative reconstruction methods improves image SNR as compared with FBP. The aim of this study was to compare FBP with iterative reconstruction, to assess the statistical power of H(2)(15)O-PET activation studies using statistical parametric mapping. For this case study, PET data originating from a bimanual motor task were reconstructed using both FBP and maximum likelihood expectation maximization (ML-EM), an iterative algorithm. Both resulting data sets were statistically analyzed using statistical parametric mapping. It was found, with this dataset, that the statistical analysis of the iteratively reconstructed data confirm the a priori expected physiological response. In addition, increased Z scores were obtained in the iteratively reconstructed data. In particular, for the expected task-related response, activation of the posterior border of the left angular gyrus, the Z score increased from 3.00 to 3.96. Furthermore, the number of statistically significant clusters doubled while their volume increased by more than 50%. In conclusion, iterative reconstruction has the potential to increase the statistical power in H(2)(15)O-PET activation studies as compared with FBP reconstruction. PMID- 11771987 TI - Somatotopic organization of the ventral and dorsal finger surface representations in human primary sensory cortex evaluated by magnetoencephalography. AB - Cortical reorganization of the subtly differentiated hand map after peripheral nerve injury might be better understood if there was a topographic conception of the homuncular representation of the dorsal finger surfaces in humans, in addition to the well-established sequential rostrocaudal array of the ventral finger aspects in cortical area 3b. In the present magnetoencephalographic study, tactile pneumatic stimulation was delivered to the fingertip and to the ventral and dorsal proximal phalanx of each digit of the dominant hand in 20 right-handed volunteers. Source localization of equivalent current dipoles underlying the recorded somatosensory evoked magnetic field was performed using a Cartesian coordinate system established by the anatomical landmarks nasion and preauricular points. Of the first major peak of each somatosensory evoked field, the region with the maximum field power (root-mean-square across channels) was selected for source reconstruction. Analysis of variance for repeated measures yielded significant results with respect to the arrangement of digits along the vertical coordinate axis, demonstrating a sequential array from the most inferiorly located D1 to the most superiorly located D5 for all different stimulus positions. This is the first study providing evidence for a sequential topographical arrangement of not only the ventral but also the dorsal surface representations of the individual digits in the human somatosensory cortex. The study contributes to a better understanding of the somatosensory hand representation in human primary cortex and provides useful information with regard to cortical plasticity studies in patients with peripheral nerve injuries at the upper extremity. PMID- 11771988 TI - Task-relevant modulation of contralateral and ipsilateral primary somatosensory cortex and the role of a prefrontal-cortical sensory gating system. AB - Electrophysiological studies have shown that task-relevant somatosensory information leads to selective facilitation within the primary somatosensory cortex (SI). The purpose of the present study was (1) to further explore the relationship between the relevancy of stimuli and activation within the contralateral and ipsilateral SI and (2) to provide further insight into the specific sensory gating network responsible for modulating neural activity within SI. Functional MRI of 12 normal subjects was performed with vibrotactile stimuli presented to the pad of the index finger. In experiment 1, the stimulus was presented to either the left or the right hand. Subjects were required to detect transient changes in stimulus frequency. In experiment 2, stimuli were presented to either the right hand alone or both hands simultaneously. Stimuli were applied either (A) passively or (B) when subjects were asked to detect frequency changes that occurred to the right hand only. In experiment 1, task-relevant somatosensory stimulation led not only to enhanced contralateral SI activity, but also to a suppression of activity in the ipsilateral SI. In experiment 2, SI activation was enhanced when stimuli were task-relevant, compared to that observed with passive input. When stimuli were presented simultaneously to both hands, only those that were task-relevant increased SI activation. This was associated with recruitment of a network of cortical regions, including the right prefrontal cortex (Brodmann area 9). We conclude that SI modulation is dependent on task relevancy and that this modulation may be regulated, at least in part, by the prefrontal cortex. PMID- 11771989 TI - Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients. AB - Twin studies point toward a substantial heritability in individual variations in the size of the human brain. However, the etiology is largely unknown. The prion protein (gene name: PRNP) aids cellular resistance to oxidative stress and neurodegeneration and is involved in neurodevelopment. This study examines the influence of a polymorphism in the PRNP gene on brain morphology in 47 healthy males and 43 male schizophrenic patients. All subjects underwent identical MRI scanning sessions followed by segmentation in cerebrospinal fluid (CSF), gray and white matter tissue, and genotyping for a biallelic polymorphism in PRNP (Met129Val). Genotype and allele frequencies did not differ between schizophrenic patients and controls but the polymorphism was associated with white matter tissue reduction (P = 0.024) and enlargement of CSF compartments (P = 0.039). These findings suggest that homozygosity for methionine at codon 129 is associated with decreased white matter tissue and larger CSF volume in right handed male healthy volunteers and schizophrenic patients. This, however, being a novel finding, should warrant further investigation. PMID- 11771990 TI - Sustained magnetic fields reveal separate sites for sound level and temporal regularity in human auditory cortex. AB - Magnetoencephalography was used to investigate the relationship between the sustained magnetic field in auditory cortex and the perception of periodic sounds. The response to regular and irregular click trains was measured at three sound intensities. Two separate sources were isolated adjacent to primary auditory cortex: One, located in lateral Heschl's gyrus, was particularly sensitive to regularity and largely insensitive to sound level. The second, located just posterior to the first in planum temporale, was particularly sensitive to sound level and largely insensitive to regularity. This double dissociation to the same stimuli indicates that the two sources represent separate mechanisms; the first would appear to be involved with pitch perception and the second with loudness. The delay of the offset of the sustained field was found to increase with interclick interval up to 200 ms at least, which suggests that the sustained field offset represents a sophisticated offset-monitoring mechanism rather than simply the cessation of stimulation. PMID- 11771991 TI - Wavelet-generalized least squares: a new BLU estimator of linear regression models with 1/f errors. AB - Long-memory noise is common to many areas of signal processing and can seriously confound estimation of linear regression model parameters and their standard errors. Classical autoregressive moving average (ARMA) methods can adequately address the problem of linear time invariant, short-memory errors but may be inefficient and/or insufficient to secure type 1 error control in the context of fractal or scale invariant noise with a more slowly decaying autocorrelation function. Here we introduce a novel method, called wavelet-generalized least squares (WLS), which is (to a good approximation) the best linear unbiased (BLU) estimator of regression model parameters in the context of long-memory errors. The method also provides maximum likelihood (ML) estimates of the Hurst exponent (which can be readily translated to the fractal dimension or spectral exponent) characterizing the correlational structure of the errors, and the error variance. The algorithm exploits the whitening or Karhunen-Loeve-type property of the discrete wavelet transform to diagonalize the covariance matrix of the errors generated by an iterative fitting procedure after both data and design matrix have been transformed to the wavelet domain. Properties of this estimator, including its Cramer-Rao bounds, are derived theoretically and compared to its empirical performance on a range of simulated data. Compared to ordinary least squares and ARMA-based estimators, WLS is shown to be more efficient and to give excellent type 1 error control. The method is also applied to some real (neurophysiological) data acquired by functional magnetic resonance imaging (fMRI) of the human brain. We conclude that wavelet-generalized least squares may be a generally useful estimator of regression models in data complicated by long memory or fractal noise. PMID- 11771992 TI - Corpus callosum shape and neuropsychological deficits in adult males with heavy fetal alcohol exposure. AB - Persons with brain damage consequent to prenatal alcohol exposure have typically been diagnosed with either fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE), depending on facial features. There is great variability of behavioral deficits within these groups. We sought to combine neuroanatomical measures with neurocognitive and neuromotor measures in criteria of greater sensitivity over the variety of consequences of alcohol exposure. To this end, midline curves of the corpus callosum were carefully digitized in three dimensions from T1-weighted MR scans of 15 adult males diagnosed with FAS, 15 with FAE, and 15 who were unexposed and clinically normal. From 5 h of neuropsychological testing we extracted 260 scores and ratings pertaining to attention, memory, executive function, fine and gross motor performance, and intelligence. Callosal midline shape was analyzed by new morphometric methods, and the relation of shape to behavior by partial least squares. The FAS and FAE subgroups have strikingly more variability of callosal shape than our normal subjects. With the excess shape variation are associated two different profiles of behavioral deficit unrelated to full-scale IQ or to the FAS/FAE distinction within the exposed subgroup. A relatively thick callosum is associated with a pattern of deficit in executive function; one that is relatively thin, with a deficit in motor function. The two combine in a very promising bipolar discrimination of the exposed from the unexposed in this sample. Thus there is considerable information in callosal form for prognosis of neuropsychological deficits in this frequently encountered birth defect. PMID- 11771993 TI - Detection versus estimation in event-related fMRI: choosing the optimal stimulus timing. AB - With the advent of event-related paradigms in functional MRI, there has been interest in finding the optimal stimulus timing, especially when the interstimulus interval is varied during the imaging run. Previous works have proposed stimulus timings to optimize either the estimation of the impulse response function (IRF) or the detection of signal changes. The purpose of this paper is to clarify that estimation and detection are fundamentally different goals and to determine the optimal stimulus timing and distribution with respect to both the accuracy of estimating the IRF and the power of detection assuming a particular hemodynamic model. Simulated stimulus distributions are varied systematically, from traditional blocked designs to rapidly varying event related designs. These simulations indicate that estimation of the hemodynamic impulse response function is optimized when stimuli are frequently alternated between task and control states, with shorter interstimulus intervals and stimulus durations, whereas the detection of activated areas is optimized by blocked designs. The stimulus timing for a given experiment should therefore be generated with the required detectability and estimation accuracy. PMID- 11771994 TI - A PET exploration of the neural mechanisms involved in reciprocal imitation. AB - Imitation is a natural mechanism involving perception-action coupling which plays a central role in the development of understanding that other people, like the self, are mental agents. PET was used to examine the hemodynamic changes occurring in a reciprocal imitation paradigm. Eighteen subjects (a) imitated the actions of the experimenter, (b) had their actions imitated by the experimenter, (c) freely produced actions, or (d) freely produced actions while watching different actions made by the experimenter. In a baseline condition, subjects simply watched the experimenter's actions. Specific increases were detected in the left STS and in the inferior parietal cortex in conditions involving imitation. The left inferior parietal is specifically involved in producing imitation, whereas the right homologous region is more activated when one's own actions are imitated by another person. This pattern of results suggests that these regions play a specific role in distinguishing internally produced actions from those generated by others. PMID- 11771995 TI - Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. AB - An anatomical parcellation of the spatially normalized single-subject high resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps. PMID- 11771996 TI - Mapping protein-protein interactions in solution by NMR spectroscopy. AB - NMR is very well suited to the study of especially weak protein-protein interactions, as no crystallization is required. The available NMR methods to this end are reviewed and illustrated with applications from the recent biochemical literature: intermolecular NOEs, cross-saturation, chemical shift perturbation, dynamics and exchange perturbation, paramagnetic methods, and dipolar orientation. Most of these methods are now routinely applied for complexes with total molecular mass of 60 kDa and can likely be applied to systems up to 1000 kDa. A substantial fraction of complexes studied show distinct effects of induced fit affecting structural and dynamical properties beyond the contact interface. PMID- 11771997 TI - Effect of ErbB2 coexpression on the kinetic interactions of epidermal growth factor with its receptor in intact cells. AB - We have extended the use of stopped-flow mixing and fluorescence anisotropy detection to investigate in real-time the effects of ErbB2 coexpression on the kinetic interactions of epidermal growth factor (EGF) with the EGF receptor. Using stable 32D-derived cell lines expressing both the EGF receptor and ErbB2, and fluorescein-labeled H22Y murine EGF (F-EGF), a series of association and dissociation experiments were performed in which the kinetic interaction of F-EGF with cells was monitored by observing time-dependent changes in fluorescence anisotropy following rapid mixing. Data were collected at various concentrations of F-EGF and multiple cell densities, using cells that express similar levels of the EGF receptor but different levels of ErbB2, and then analyzed by fitting to a two independent receptor-class model using global analysis techniques. The recovered kinetic parameters indicated that the coexpression of ErbB2 had relatively modest effects on recovered rate constants and calculated K(d) values, but a significant effect on the fraction of receptors associated with the high affinity receptor class. This effect on the fraction of high-affinity receptors depended on the relative expression of ErbB2, as higher ErbB2 expression levels correlated with a larger fraction of high-affinity receptors. Further, the increase in the fraction of high-affinity receptors due to the presence of ErbB2 occurred without any change in the total number of EGF binding sites per cell. Thus, we have identified modulation of the relative populations of high- and low affinity classes of EGF receptors as a consequence of coexpression of ErbB2 with the EGF receptor. PMID- 11771998 TI - An interdomain linker increases the thermostability and decreases the calcium affinity of the calmodulin N-domain. AB - A hydrophobic core is a widely accepted determinant of protein stability. However, regulatory proteins undergoing ligand-induced conformational switching may expose interior residues to solvent and cannot afford to be extremely rigid. Optimizing the energetic balance between stability and binding is challenging. The addition of five interdomain residues to rat and Paramecium calmodulin N domain fragments (residues 1-75) increased their thermostability by 9 degrees C and lowered their calcium affinity by a factor of 4. This demonstrates that the flexible linker regulates functional properties as well as tethering the neighboring domains and that protein stability may be increased markedly by minor modifications of the C-terminus. The sensitivity of this domain to few and conservative variations in helices A and D (D2E, S17A, T70S and M71L) is demonstrated by the rat CaM fragments having lower stability and higher calcium affinity than fragments of the same length derived from Paramecium CaM. PMID- 11771999 TI - Overexpression and structural study of the cathelicidin motif of the protegrin-3 precursor. AB - Numerous precursors of antibacterial peptides with unrelated sequences share a similar prosequence of 96-101 residues, referred to as the cathelicidin motif. The structure of this widespread motif has not yet been reported. The cathelicidin motif of protegrin-3 (ProS) was overexpressed in Escherichia coli as a His-tagged protein to facilitate its purification. The His tag was then removed by thrombin cleavage. In addition, the complete proprotegrin-3 (ProS-PG-3) (120 residues) was overexpressed in baculovirus-infected insect cells. As it contained the antibacterial peptide protegrin-3 in its C-terminal part, ProS-PG-3 contained four disulfide bonds. At neutral pH, ProS and ProS-PG-3 adopted two slowly exchanging conformations that existed in a ratio of 55/45. This ratio was progressively modified at acidic pH to reach a 90/10 value at pH 3.0, suggesting that electrostatic interactions are involved in such a conformational change. Therefore, the structural study of the main conformer was undertaken at pH 3.0 by circular dichroism, mass spectrometry, and homo- and heteronuclear NMR. In parallel, a model for the ProS structure was built from the X-ray structure of the chicken cystatin. ProS and the chicken cystatin share two conserved disulfide bonds as well as a high conservation of hydrophobic residues. The ProS model features the conservation of a hydrophobic core made of the interface between the N-terminal helix and the wrapping beta-sheet. Although the full assignment of the main conformer of ProS could not be obtained, available NMR data validated the presence of the N-terminal helix and of a four-stranded beta-sheet, in agreement with the cystatin fold. Moreover, we clearly demonstrated that ProS and ProS-PG-3 share the same global structure, suggesting that the presence of the highly constrained beta-hairpin of protegrin does not significantly modify the structure of the cathelicidin motif of the protegrin precursor. PMID- 11772000 TI - Structure of the Rhodobacter sphaeroides light-harvesting 1 beta subunit in detergent micelles. AB - The light harvesting 1 antenna (LH1) complex from Rhodobacter sphaeroides funnels excitation energy to the photosynthetic reaction center. Our ultimate goal is to build up the structure of LH1 from structures of its individual subunits, much as the antenna can self-assemble from its components in membrane-mimicking detergent micelles. The beta subunit adopts a nativelike conformation in Zwittergent 3:12 micelles as demonstrated by its ability to take the first step of assembly, binding BChl a. Multidimensional NMR spectroscopy shows that the beta subunit folds as a helix((L12-S25))-hinge((G26-W28))-helix((L29-W44)) structure with the helical regions for the 10 lowest-energy structures having backbone rmsds of 0.26 and 0.24 A, respectively. Mn(2+) relaxation data and the protein-detergent NOE pattern show the C-terminal helix embedded in the micelle and the N-terminal helix lying along the detergent micelle surface with a 60 degrees angle between their long axes. (15)N relaxation data for residues L12-W44 are typical of a well ordered protein with a correlation time of 8.25 +/- 2.1 ns. The presence of the hinge region placing the N-terminal helix along the membrane surface may be the structural feature responsible for the functional differences observed between the LH1 and LH2 beta subunits. PMID- 11772001 TI - NMR structure of the [2Fe-2S] ferredoxin domain from soluble methane monooxygenase reductase and interaction with its hydroxylase. AB - The soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath) is a multicomponent enzyme system required for the conversion of methane to methanol. It comprises a hydroxylase, a regulatory protein, and a reductase. The reductase contains two domains: an NADH-binding and FAD-containing flavin domain and a ferredoxin (Fd) domain carrying a [2Fe-2S] cofactor. Here, we report the solution structure of the reduced form of the 98-amino acid Fd domain (Blazyk, J. L., and Lippard, S. J. Unpublished results) determined by nuclear magnetic resonance (NMR) spectroscopy and restrained molecular dynamics calculations. The structure consists of six beta strands arranged into two beta sheets as well as three alpha helices. Two of these helices form a helix-proline-helix motif, unprecedented among [2Fe-2S] proteins. The [2Fe-2S] cluster is coordinated by the sulfur atoms of cysteine residues 42, 47, 50, and 82. The 10.9 kDa ferredoxin domain of the reductase protein transfers electrons to carboxylate-bridged diiron centers in the 251 kDa hydroxylase component of sMMO. The binding of the Fd domain with the hydroxylase was investigated by NMR spectroscopy. The hydroxylase binding surface on the ferredoxin protein has a polar center surrounded by patches of hydrophobic residues. This arrangement of amino acids differs from that by which previously studied [2Fe-2S] proteins interact with their electron transfer partners. The critical residues on the Fd domain involved in this binding interaction map well onto the universally conserved residues of sMMO enzymes from different species. We propose that the [2Fe-2S] domains in these other sMMO systems have a fold very similar to the one found here for M. capsulatus (Bath) MMOR-Fd. PMID- 11772002 TI - Carboxypeptidase E, a prohormone sorting receptor, is anchored to secretory granules via a C-terminal transmembrane insertion. AB - Carboxypeptidase E (CPE) is a sorting receptor that directs the prohormone pro opiomelanocortin (POMC) to the regulated secretory pathway, and is also a prohormone processing enzyme in neuro/endocrine cells. It has been suggested that the 25 C-terminal amino acids are necessary for the binding of CPE to secretory granule membranes, but its orientation in the membrane is not known. In this study, we examined the structure and orientation of the membrane-binding domain at the C-terminus of CPE. In vitro experiments using model membranes demonstrated that the last 22 amino acids of CPE (CP peptide) insert in a shallow orientation into lipid bilayers at low pH. Circular dichroism analysis indicated that the CP peptide adopts a partial alpha-helical configuration at low pH, and helix content increases when it is bound to lipid. Protease protection experiments, immunolabeling, and immunoisolation of intact secretory granules with a C terminal antibody revealed a cytoplasmic domain in CPE, consistent with a transmembrane orientation of this protein. We conclude that the membrane-binding domain of CPE must adopt an alpha-helical configuration to bind to lipids, and that CPE may require another integral membrane "chaperone" protein to insert through the lipid bilayer in a transmembrane fashion. PMID- 11772003 TI - NMR and modeling studies of a synthetic extracellular loop II of the kappa opioid receptor in a DPC micelle. AB - This paper provides the first direct experimental evidence for the secondary structural features of the putative second extracellular loop (ECL II) of the kappa opioid receptor through a synthetic peptide mimic in a DPC micelle environment. These studies indicate that residues V(6)-A(15) of the ECL II peptide adopt a well-defined helical structure analogous to that formed by V(201) C(210) of the native receptor. Moreover, a beta-turn around the D(22) (D(217)) and D(23) (D(218)) residues represents another feature of the ECL II. The NMR and fluorescent data also suggest the location of the two helical turns of TM V and the approximate location of the C-terminal end of the TM IV of the kappa opioid receptor. We modeled the kappa opioid receptor including the extracellular region of the receptor. The model of the ECL II utilized the information obtained from the NMR structural analysis of the ECL II peptide in a DPC micelle solution and the molecular dynamic simulations in a biphasic membrane environment. Our discovery of this amphiphilic helical region in the ECL II peptide by NMR and molecular modeling studies provides direct evidence that the sequence of residues V(201)-C(210) is likely to be the helical region that interacts with Dynorphin (Dyn) A [Paterlini, G., Portoghese, P. S., and Ferguson, D. M. (1997) J. Med. Chem. 40, 3254-3262]. We believe that this work offers further insight into the structural characteristics of the extracellular portions of the seven-TM kappa opioid receptor. PMID- 11772004 TI - UV resonance Raman and circular dichroism studies of a DNA duplex containing an A(3)T(3) tract: evidence for a premelting transition and three-centered H-bonds. AB - The presence of A(n) and A(n)T(n) tracts in double-helical sequences perturbs the structural properties of DNA molecules, resulting in the formation of an alternate conformation to standard B-DNA known as B'-DNA. Evidence for a transition occurring prior to duplex melting in molecules containing A(n) tracts was previously detected by circular dichroism (CD) and calorimetric studies. This premelting transition was attributed to a conformational change from B'- to B DNA. Structural features of A(n) and A(n)T(n) tracts revealed by X-ray crystallography include a large degree of propeller twisting of adenine bases, narrowed minor grooves, and the formation of three-centered H-bonds between dA and dT bases. We report UV resonance Raman (UVRR) and CD spectroscopic studies of two related DNA dodecamer duplexes, d(CGCAAATTTGCG)(2) (A(3)T(3)) and d(CGCATATATGCG)(2) [(AT)(3)]. These studies address the presence of three centered H-bonds in the B' conformation and gauge the impact of these putative H bonds on the structural and thermodynamic properties of the A(3)T(3) duplex. UVRR and CD spectra reveal that the premelting transition is only observed for the A(3)T(3) duplex, is primarily localized to the dA and dT bases, and is associated with base stacking interactions. Spectroscopic changes associated with the premelting transition are not readily detectable for the sugar-phosphate backbone or the cytosine and guanosine bases. The temperature-dependent concerted frequency shifts of dA exocyclic NH(2) and dT C4=O vibrational modes suggest that the A(3)T(3) duplex forms three-centered hydrogen bonds at low temperatures, while the (AT)(3) duplex does not. The enthalpy of this H-bond, estimated from the thermally induced frequency shift of the dT C4=O vibrational mode, is approximately 1.9 kJ/mol or 0.46 kcal/mol. PMID- 11772005 TI - Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor. AB - Tissue factor pathway inhibitor (TFPI) inhibits the activity of coagulation factor VIIa and Xa through its K1 and K2 domain, respectively, and the inhibitory activity is enhanced by heparin. The function of the K3 domain of TFPI has not been established, but the domain probably harbors a heparin binding site (HBS-2). We determined the three-dimensional solution structure of the TFPI K3 domain (Glu182-Gly242) by heteronuclear multidimensional NMR. The results showed that the molecule is composed of one antiparallel beta-sheet and one alpha-helix, and in overall structure is very similar to the K2 domain, with the rms deviation of 1.55 A for the 58 defined C(alpha) positions. However, the surface electrostatic properties of both domains are different each other. The lack of inhibitory activity of the K3 domain is explained by the absence of electrostatic interaction with factor Xa over a large surface area. A titration experiment with size-fractionated heparin showed that a heparin binding site was located in the vicinity of the alpha-helix. In this region, a positively charged cluster is formed by Lys213, Lys232, and Lys240, and the negatively charged sulfate groups of heparin bind there. The enhancement of inhibitory activity by heparin probably was not due to a conformational change to TFPI itself. It is likely that heparin simply increases the local concentration of TFPI on the cell surface and stabilizes the initial complex that forms. PMID- 11772006 TI - Actin cross-linking and inhibition of the actomyosin motor. AB - Intrastrand cross-linking of actin filaments by ANP, N-(4-azido-2-nitrophenyl) putrescine, between Gln-41 in subdomain 2 and Cys-374 at the C-terminus, was shown to inhibit force generation with myosin in the in vitro motility assays [Kim et al. (1998) Biochemistry 37, 17801-17809]. To clarify the immobilization of which of these two sites inhibits the actomyosin motor, the properties of actins with partially overlapping cross-linked sites were examined. pPDM (N,N'-p phenylenedimaleimide) and ABP [N-(4-azidobenzoyl) putrescine] were used to obtain actin filaments cross-linked ( approximately 50%) between Cys-374 and Lys-191 (interstrand) and Gln-41 and Lys-113 (intrastrand), respectively. ANP, ABP, and pPDM cross-linked filaments showed similar inhibition of their sliding speeds and force generation with myosin ( approximately 25%) in the in vitro motility assays. In analogy to ANP cross-linking of actin, pPDM and ABP cross-linkings did not change the strong S1 binding to actin and the V(max) and K(m) parameters of actomyosin ATPase. The similar effects of these three cross-linkings reveal the tight coupling between structural elements of the subdomain 2/subdomain 1 interface and show the importance of its dynamic flexibility to force generation with myosin. The possibility that actin cross-linkings inhibit rate-limiting steps in motion and force generation during myosin cross-bridge cycle was tested in stopped-flow experiments. Measurements of the rates of mantADP release from actoS1 and ATP-induced dissociation of actoS1 did not reveal any differences between un-cross-linked and ANP cross-linked actin in these complexes. These findings are discussed in terms of the uncoupling between force generation and other aspects of actomyosin interactions due to a constrained dynamic flexibility of the subdomain 2/subdomain 1 interface in cross-linked actin filaments. PMID- 11772007 TI - Model for the catalytic domain of the proofreading epsilon subunit of Escherichia coli DNA polymerase III based on NMR structural data. AB - The DNA polymerase III holoenzyme (HE) is the primary replicative polymerase of Escherichia coli. The epsilon subunit of the HE complex provides the 3' exonucleolytic proofreading activity for this enzyme complex. epsilon consists of two domains: an N-terminal domain containing the proofreading exonuclease activity (residues 1-186) and a C-terminal domain required for binding to the polymerase (alpha) subunit (residues 187-243). Multidimensional NMR studies of (2)H-, (13)C-, and (15)N-labeled N-terminal domains (epsilon186) were performed to assign the backbone resonances and measure H(N)-H(N) nuclear Overhauser effects (NOEs). NMR studies were also performed on triple-lableled [U (2)H,(13)C,(15)N]epsilon186 containing Val, Leu, and Ile residues with protonated methyl groups, which allowed for the assignment of H(N)-CH(3) and CH(3)-CH(3) NOEs. Analysis of the (13)C(alpha), (13)C(beta), and (13)CO shifts, using chemical shift indexing and the TALOS program, allowed for the identification of regions of the secondary structure. H(N)-H(N) NOEs provided information on the assembly of the extended strands into a beta-sheet structure and confirmed the assignment of the alpha helices. Measurement of H(N)-CH(3) and CH(3)-CH(3) NOEs confirmed the beta-sheet structure and assisted in the positioning of the alpha helices. The resulting preliminary characterization of the three-dimensional structure of the protein indicated that significant structural homology exists with the active site of the Klenow proofreading exonuclease domain, despite the extremely limited sequence homology. On the basis of this analogy, molecular modeling studies of epsilon186 were performed using as templates the crystal structures of the exonuclease domains of the Klenow fragment and the T4 DNA polymerase and the recently determined structure of the E. coli Exonuclease I. A multiple sequence alignment was constructed, with the initial alignment taken from the previously published hidden Markov model and NMR constraints. Because several of the published structures included complexed ssDNA, we were also able to incorporate an A-C-G trinucleotide into the epsilon186 structure. Nearly all of the residues which have been identified as mutators are located in the portion of the molecule which binds the DNA, with most of these playing either a catalytic or structural role. PMID- 11772008 TI - Nucleotide binding to pig muscle 3-phosphoglycerate kinase in the crystal and in solution: relationship between substrate antagonism and interdomain communication. AB - Binding constants for the nucleotide substrates were determined in two different crystalline forms of pig muscle 3-phosphoglycerate kinase (PGK): the binary complex with 3-phosphoglycerate (3-PG) in which the two domains are in an open conformation (Harlos, Vas, and Blake (1992) Proteins, 12, 133-144) and the ternary complex with 3-PG and the Mg salt of the ATP analogue, beta,gamma methyleneadenosine-5'-triphosphate (AMP-PCP), the structure of which is under resolution. Competitive titrations have been performed in the presence of the chromophoric analogue of ATP, 2'3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP), similar to those previously carried out in solution, where a weakening of the binding of the nucleotide substrates in the presence of the other substrate, 3-PG, has been observed (Vas, Merli, and Rossi (1994) Biochem. J. 301, 885-891). Here the K(d) values for MgADP were found to be 0.096 +/- 0.021 and 0.045 +/- 0.016 mM, respectively, for the crystals of the binary and ternary complexes. Both K(d) values are significantly smaller than the one obtained in solution in the presence of 3-PG (0.38 +/- 0.05 mM) and are close to the values determined in solution in the absence of 3-PG (0.06 +/- 0.01 mM). Thus, the "substrate antagonism" observed in solution is not present in either of the investigated crystal forms. Further nucleotide binding studies with the solubilized enzyme have shown that 3-PG has no effect on ADP (Mg(2+)-free) binding (K(d) = 0.34 +/- 0.05 mM), while it weakens MgADP binding. Thus, 3-PG abolishes the strengthening effect of the Mg(2+) ion on the binding of ADP. This phenomenon is apparently due to the interaction between the carboxyl group of 3-PG and the protein, since the carboxyl-lacking analogue glycerol-3-phosphate has no detectable effect on MgADP binding. Comparison of the crystallographic data of different PGK binary (with either 3-PG or MgADP) and ternary (with both 3-PG and MgADP) complexes, having open and closed conformations, respectively, provides a possible structural explanation of the substrate antagonism. We suggest that the specific interaction between the 3-PG carboxylic group and a conserved arginine side chain is changed during domain closure, and, through interdomain communication, this change may be transmitted to the site in which Mg(2+) binds the ADP phosphates. This effect is abolished in the crystals of pig muscle PGK, in which lattice forces stabilize the open domain conformation. PMID- 11772009 TI - Effect of histidine 6 protonation on the active site structure and electron transfer capabilities of pseudoazurin from Achromobacter cycloclastes. AB - The paramagnetic (1)H NMR spectrum of Cu(II) pseudoazurin [PACu(II)] contains eight directly observed hyperfine-shifted resonances which we have assigned using saturation transfer experiments on a 1:1 mixture of PACu(I) and PACu(II). The spectrum exhibits a number of similarities to those of other cupredoxins, but differences are found concerning the Cu-S(Met) interaction. The spectrum is dependent on pH* in the range 8.5-4.5 (pK(a)* 6.4), and a conformational change involving movement of the copper ion away from the Met toward the equatorial ligands, as a consequence of protonation of the surface His6 residue, is identified. Corresponding changes are also seen in the UV/vis spectrum. The protonation/deprotonation equilibrium of His6 influences the reduction potential of the protein in the same pH range. The self-exchange rate constant of PACu at pH* 6.0 (25 degrees C) is considerably smaller (1.1 x 10(3) M(-1) s(-1)) than the value obtained at pH* 7.6 (3.7 x 10(3) M(-1) s(-1)). The effect on the self exchange reactivity is mainly due to an alteration in the reorganization energy of the copper site brought about by the structural change resulting from His6 protonation. PMID- 11772010 TI - Equilibrium and stop-flow kinetic studies of fluorescently labeled DNA substrates with DNA repair proteins XPA and replication protein A. AB - Nucleotide excision repair (NER) is a crucial pathway in the maintenance of genome stability requiring at least two dozen proteins. XPA and RPA have essential roles in the damage recognition step of NER. To better understand the mechanism of their interactions with DNA, we utilized equilibrium and stop-flow kinetic approaches with fluorescently labeled oligonucleotides. Fluorescein is a bona fide NER lesion because a circular plasmid with a single defined fluorescein was repaired by efficient extracts from Xenopus oocyte nuclei. Single-stranded and double-stranded oligonucleotides 5'-labeled with fluorescein were used in the subsequent studies. Oligonucleotide fluorescence was quenched upon specific binding to full-length recombinant Xenopus XPA (xXPA) and/or human RPA. The binding was highly sensitive to the buffer conditions. Analysis of equilibrium binding data with ds DNA and xXPA revealed a single dissociation constant (K(d)) of 24.4 nM. Stopped-flow kinetic experiments were described by a first-order on rate constant k(on) of 9.03 x 10(8) M(-1) s(-1) and k(off) of 26.1 s(-1). From the ratio of off-rate to on-rate, a calculated K(d) of 28.9 nM was obtained, revealing that the kinetic and equilibrium studies were consistent. The affinity of xXPA for ds undamaged DNA determined in our spectrofluorometry experiments was up to 3 orders of magnitude higher than previously reported values using different substrates, conditions, and assays [gel-shifts (EMSA), filter-binding, anisotropy, and surface plasmon resonance]. The same substrate DNA containing a 4 bp mismatch in the middle yielded a K(d) five times higher (158 nM), indicating weaker binding by xXPA. The differences in K(d) values for these two substrates were mainly attributable to the k(on), rather than k(off) rates. Fluorescence intensity changes upon interaction of xXPA with ss 50-mer were too low to calculate an accurate K(d). Although recombinant human RPA binding to the ds 50 mer was very weak (K(d) > 1 mM), stop-flow and equilibrium measurements to ss oligonucleotide yielded K(d) values of 96 and 20.3 nM, respectively, which correlated with previously reported values using gel mobility shift assays and a similarly sized poly-dT. Equilibrium and stop-flow measurements to the cognate and mismatched ds oligonucleotides using both xXPA and hRPA yielded a 2- to 3 fold increase in the K(d). PMID- 11772011 TI - Comparative proteomics as a new tool for exploring human mitochondrial tRNA disorders. AB - More than 70 different point mutations in human mitochondrial tRNA genes are correlated with severe disorders, including fatal cardiopathies, encephalopathies, myopathies, and others. So far, investigation of the molecular impact(s) of mutations has focused on the affected tRNA itself by seeking structural and/or functional perturbations capable of interfering with synthesis of the 13 mitochondrion-encoded subunits of respiratory chain complexes. Here, a proteomic approach was used to investigate whether such mutations would affect the pattern of mitochondrial proteins at a broader level. Analysis of several hundred mitochondrial proteins from sibling cybrid cell lines by two-dimensional electrophoresis, an approach that takes into account all regulatory steps of mitochondrial and nuclear gene expression, indeed reveals a number of up- and downregulated proteins when healthy and single-point-mutation-carrying mitochondria representative of either MELAS or MERRF syndrome were compared. Assignment by mass spectrometry of the two proteins which exhibit obvious large quantitative decreases in the levels of both pathologic mitochondria identified nuclear-encoded subunits of cytochrome c oxidase, a respiratory chain complex. This clearly shows a linkage between the effects of mutations in mitochondrial tRNA genes and the steady-state level of nuclear-encoded proteins in mitochondria. It opens new routes toward a large-scale exploration of potential proteic partners involved in the genotype-phenotype correlation of mitochondrial disorders. PMID- 11772012 TI - Effects of nucleotide analogues on Euplotes aediculatus telomerase processivity: evidence for product-assisted translocation. AB - Telomerase is a unique ribonucleoprotein that reverse transcribes a defined region of its RNA subunit onto the ends of eukaryotic chromosomes. The product of telomerase, telomeric DNA, is typically a G-rich repeated sequence, (TTTTGGGG)(n) in the ciliate Euplotes aediculatus and (TTAGGG)(n) in humans. Telomerase can extend oligonucleotide primers in vitro in a processive fashion. We used dNTP analogues to study the structure-activity relationship between substrate nucleotides and processivity of telomerase from E. aediculatus. Several analogues, including 2'-deoxyuridine triphosphate (dUTP), 2'-deoxyinosine triphosphate (dITP), and 7-deaza-2'-deoxyguanosine triphosphate (7-deaza-dGTP), were good substrates for telomerase with K(m) and V(max) values near those of the natural substrates, dTTP and dGTP. However, telomerase processivity was affected with these substrates, decreasing in the order dUTP > 7-deaza-dGTP > dITP. Telomerase did not completely reverse transcribe the template when dITP was the substrate, and it efficiently extended a primer by the addition of two repeats when 7-deaza-dGTP and dUTP were utilized. When the same nucleotide analogues were incorporated into the primers, no effects were observed except in the case of a 3'-terminal deoxyinosine. The data support a model that includes the formation of an intramolecular secondary structure within the product DNA to facilitate translocation. The most likely structure is a G-G hairpin. PMID- 11772013 TI - Kinetic mechanism of elongation factor Ts-catalyzed nucleotide exchange in elongation factor Tu. AB - The interaction of Escherichia coli elongation factor Tu (EF-Tu) with elongation factor Ts (EF-Ts) and guanine nucleotides was studied by the stopped-flow technique, monitoring the fluorescence of tryptophan 184 in EF-Tu or of the mant group attached to the guanine nucleotide. Rate constants of all association and dissociation reactions among EF-Tu, EF-Ts, GDP, and GTP were determined. EF-Ts enhances the dissociation of GDP and GTP from EF-Tu by factors of 6 x 10(4) and 3 x 10(3), respectively. The loss of Mg(2+) alone, without EF-Ts, accounts for a 150-300-fold acceleration of GDP dissociation from EF-Tu.GDP, suggesting that the disruption of the Mg(2+) binding site alone does not explain the EF-Ts effect. Dissociation of EF-Ts from the ternary complexes with EF-Tu and GDP/GTP is 10(3) 10(4) times faster than from the binary complex EF-Tu.EF-Ts, indicating different structures and/or interactions of the factors in the binary and ternary complexes. Rate constants of EF-Ts binding to EF-Tu in the free or nucleotide bound form or of GDP/GTP binding to the EF-Tu.EF-Ts complex range from 0.6 x 10(7) to 6 x 10(7) M(-1) s(-1). At in vivo concentrations of nucleotides and factors, the overall exchange rate, as calculated from the elemental rate constants, is 30 s(-1), which is compatible with the rate of protein synthesis in the cell. PMID- 11772014 TI - Human p53 phosphorylation mimic, S392E, increases nonspecific DNA affinity and thermal stability. AB - DNA binding is crucial to the protective role of the tumor suppressor protein p53, a nuclear phosphoprotein and transcription factor. The mutant human p53 protein S392E is a phosphorylation mimic that has been previously demonstrated to represent an "activated" form of p53 in both in vivo and in vitro assays [Hupp and Lane (1995) J. Biol. Chem. 270, 18165; Hao et al. (1996) J. Biol. Chem. 271, 29380]. Herein, we describe an analysis of structural and functional differences between this mutant and the wild-type protein. Structurally, the S392E protein exhibits increased thermal stability compared to wild-type p53, as monitored by circular dichroism and conformational antibody Ab1620 reactivity. These structural effects include alterations to the core DNA binding domain, remote in sequence space from the site of mutation. Functionally, the S392E mutation does not increase p53 binding to its 20 bp consensus DNA sequence in the absence of nonspecific DNA additives. In contrast, affinity of S392E for a 20 bp nonspecific DNA sequence is enhanced. Embedding 20 bp consensus DNA in the context of longer DNA sequences does not substantially alter S392E affinity, whereas wild-type affinity for these DNAs decreases with increased proportion of nonspecific DNA. These differences may account for the S392E "activated" phenotype and illuminate the role of this modified p53 in vivo. PMID- 11772015 TI - Reconstitution of nucleosomes with histone macroH2A1.2. AB - MacroH2A histones have an unusual hybrid structure, consisting of an N-terminal domain that is approximately 65% identical to a full-length histone H2A and a large C-terminal nonhistone domain. To develop an in vitro approach for investigating the effects of macroH2A proteins on chromatin structure and function, we reconstituted nucleosomes with recombinant macroH2A1.2, substituting for conventional H2A. Recombinant macroH2A1.2 was able to efficiently replace both of the conventional H2As in reconstituted nucleosomes. The substitution of macroH2A1.2 for H2A did not appear to grossly perturb the basic structure of the nucleosome core, as assessed by sedimentation and by digestion with micrococcal nuclease or DNase I. However, two differences were observed. First, the region around the midpoint of the nucleosomal core DNA was more resistant to digestion by DNase I in nucleosome core particles reconstituted with macroH2A1.2. Second, preparations of core particles reconstituted with macroH2A1.2 had a greater amount of material that sedimented more rapidly than mononucleosomes, suggesting that macroH2A1.2 may promote interactions between nucleosomes. Recombinant macroH2A proteins should be valuable tools for examining the effects of macroH2A on nucleosome and chromatin structure. PMID- 11772016 TI - Involvement of protein kinase A in the phosphorylation of spermatidal protein TP2 and its effect on DNA condensation. AB - Rat spermatidal protein TP2 is rich in serine residues and has several potential sites for phosphorylation by different protein kinases. Recombinant TP2 is phosphorylated upon incubation in vitro with salt extract of testicular sonication resistant nuclei (SRN) (representing elongating and elongated spermatids). The major phosphorylation sites were localized to the C-terminal, V8 protease-derived, fragment (residues 87-114). Phosphorylation experiments with the wild type and different site-specific mutants of TP2 revealed that serine 109 and threonine 101 are the phosphorylation sites. Phosphorylation of the C terminal fragment of TP2 was also demonstrated in vivo. Phosphorylation was not stimulated by either protein kinase C activators or cGMP but was inhibited by protein kinase A inhibitor (PKI) peptide, showing the involvement of protein kinase A in the phosphorylation of TP2. Phosphorylation of TP2 greatly reduced its DNA condensation property. TP2 when complexed with DNA was not a good substrate for phosphorylation by PKA. Dephosphorylation of the DNA-TP2 complex by calf intestinal alkaline phosphatase restored the DNA condensation property to a level equivalent to that observed with TP2. The physiological significance of the phosphorylation-dephosphorylation cycle is discussed with reference to the two domain model of TP2. PMID- 11772017 TI - Neuronal nitric oxide synthase: substrate and solvent kinetic isotope effects on the steady-state kinetic parameters for the reduction of 2,6-dichloroindophenol and cytochrome c(3+). AB - The neuronal nitric oxide synthase (nNOS) basal and calmodulin- (CaM-) stimulated reduction of 2,6-dichloroindophenol (DCIP) and cytochrome c(3+) follow ping-pong mechanisms [Wolthers and Schimerlik (2001) Biochemistry 40, 4722-4737]. Primary deuterium [NADPH(D)] and solvent deuterium isotope effects on the kinetic parameters were studied to determine rate-limiting step(s) in the kinetic mechanisms for the two substrates. nNOS was found to abstract the pro-R (A-side) hydrogen from NADPH. Values for (D)V and (D)(V/K)(NADPH) were similar for the basal (1.3-1.7) and CaM-stimulated (1.5-2.1) reduction of DCIP, while (D)V (2.1 2.8) was higher than (D)(V/K)(NADPH) (1.1-1.5) for cytochrome c(3+) reduction with and without CaM. This suggests that the rate of the reductive half-reaction (NADPH oxidation) rather than that of the oxidative half-reaction (reduction of DCIP or cytochrome c(3+)) limits the overall reaction rate. A value for (D)(V/K)(NADPH) close to 1 indicates the intrinsic isotope effect on hydride transfer is suppressed by a slower step in the reductive half-reaction. The oxidative half-reaction is insensitive to NADPD isotope effects as both (D)(V/K)(DCIP) and (D)(V/K)(cytc) equal 1 within experimental error. Large solvent kinetic isotope effects (SKIE) observed for (V/K)(cytc) for basal (approximately 8) and CaM-stimulated (approximately 31) reduction of cytochrome c(3+) suggest that proton uptake from the solvent limits the rate of the oxidative half-reaction. This step does not severely limit the overall reaction rate as (D2O)V equaled 2 and (D2O)(V/K)(NADPH) was between 0.9 and 1.3 for basal and CaM-stimulated cytochrome c(3+) reduction. PMID- 11772018 TI - Effects of Ca(2+)-activated calmodulin on neuronal nitric oxide synthase reductase activity and binding of substrates: pH dependence of kinetic parameters. AB - The pH dependence of basal and calmodulin- (CaM-) stimulated neuronal nitric oxide synthase (nNOS) reduction of 2,6-dichloroindophenol (DCIP) and cytochrome c(3+) was investigated. The wave-shaped log V versus pH profile revealed that optimal DCIP reduction occurred when a group, pK(a) of 7.6-7.8, was ionized. The (V/K)(NADPH) and (V/K)(DCIP) versus pH profiles increased with the protonation of a group with a pK(a) of 6.5 or 5.9 and the ionization of two groups with the same pK(a) of 7.5 or 7.0, respectively. (V/K)(DCIP) decreased with the ionization of a group, pK(a) of 9.0. Similar V, (V/K)(NADPH), and (V/K)(DCIP) versus pH profiles for DCIP reduction were obtained with and without CaM, indicating that CaM does not influence ionizable groups involved in catalysis or substrate binding. In contrast, CaM affected the pH dependence of cytochrome c(3+) reduction. The wave shaped log V versus pH profile for basal cytochrome c(3+) reduction revealed that ionization of a group, pK(a) of 8.6, increased catalysis. Log V for CaM stimulated cytochrome c(3+) reduction displayed a bell-shaped pH dependence with the protonation of a group with a pK(a) of 6.4 and the ionization of a group with a pK(a) of 9.3, resulting in a loss of activity. The log(V/K)(cytc) versus pH profiles with and without CaM were bell-shaped with the ionization of a group at pK(a) of 7.1 or 7.6 (CaM) or pK(a) of 9.4 or 9.6 (CaM), increasing and decreasing (V/K)(cytc). These results suggest that CaM may change the nature of the rate limiting catalytic steps or ionizable groups involved in cytochrome c(3+) reduction. PMID- 11772019 TI - Probing the role of the chloride ion in the mechanism of human pancreatic alpha amylase. AB - Human pancreatic alpha-amylase (HPA) is a member of the alpha-amylase family involved in the degradation of starch. Some members of this family, including HPA, require chloride for maximal activity. To determine the mechanism of chloride activation, a series of mutants (R195A, R195Q, N298S, R337A, and R337Q) were made in which residues in the chloride ion binding site were replaced. Mutations in this binding site were found to severely affect the ability of HPA to bind chloride ions with no binding detected for the R195 and R337 mutant enzymes. X-ray crystallographic analysis revealed that these mutations did not result in significant structural changes. However, the introduction of these mutations did alter the kinetic properties of the enzyme. Mutations to residue R195 resulted in a 20-450-fold decrease in the activity of the enzyme toward starch and shifted the pH optimum to a more basic pH. Interestingly, replacement of R337 with a nonbasic amino acid resulted in an alpha-amylase that no longer required chloride for catalysis and has a pH profile similar to that of wild-type HPA. In contrast, a mutation at residue N298 resulted in an enzyme that had much lower binding affinity for chloride but still required chloride for maximal activity. We propose that the chloride is required to increase the pK(a) of the acid/base catalyst, E233, which would otherwise be lower due to the presence of R337, a positively charged residue. PMID- 11772020 TI - Mouse folylpoly-gamma-glutamate synthetase isoforms respond differently to feedback inhibition by folylpolyglutamate cofactors. AB - Folylpoly-gamma-glutamate synthetase (FPGS) is the enzyme responsible for metabolic trapping of reduced folate cofactors in cells for use in nucleotide and amino acid biosynthesis. There are two isoforms of FPGS expressed in mouse tissues, one is expressed in differentiated tissue, principally liver and kidney, and the other in all rapidly proliferating cell types. The present study sought the functional difference that would explain the evolution of two mouse FPGS species. Recombinant cytosolic mouse isozymes were compared with respect to steady state kinetics, chain length of polyglutamate derivatives formed, and end product inhibition by the major reduced folylpentaglutamate cofactors. Both isoforms were equally effective in catalyzing the addition of a mole of glutamic acid to reduced folate monoglutamate substrates. Each isoform was also capable of forming long chain polyglutamate derivatives of the model folate, 5,10 dideazatetrahydrofolate. In contrast, the FPGS isoform derived from rapidly proliferating tissue was much more sensitive to inhibition by (6R)-5,10-CH(2) H(4)PteGlu(5) and (6S)-H(4)PteGlu(5) than the isoform expressed in differentiated tissues, as demonstrated by 13- and 6-fold lower inhibition constants (K(i)), respectively. Interestingly, each isozyme was equally sensitive to inhibition by (6R)-10-CHO-H(4)PteGlu(5). We drew the conclusion that the decreased sensitivity of the FPGS expressed in mouse liver and kidney to feedback inhibition by 5,10 CH(2)-H(4)PteGlu(5-6) and H(4)PteGlu(5-6) may have evolved to permit accumulation of a larger folate cofactor pool than that found within rapidly proliferating tissue. PMID- 11772021 TI - E. coli MEP synthase: steady-state kinetic analysis and substrate binding. AB - 2-C-Methyl-D-erythritol-4-phosphate synthase (MEP synthase) catalyzes the rearrangement/reduction of 1-D-deoxyxylulose-5-phosphate (DXP) to methylerythritol-4-phosphate (MEP) as the first pathway-specific reaction in the MEP biosynthetic pathway to isoprenoids. Recombinant E. coli MEP was purified by chromatography on DE-52 and phenyl-Sepharose, and its steady-state kinetic constants were determined: k(cat) = 116 +/- 8 s(-1), K(M)(DXP) = 115 +/- 25 microM, and K(M)(NADPH) = 0.5 +/- 0.2 microM. The rearrangement/reduction is reversible; K(eq) = 45 +/- 6 for DXP and MEP at 150 microM NADPH. The mechanism for substrate binding was examined using fosmidomycin and dihydro-NADPH as dead end inhibitors. Dihydro-NADPH gave a competitive pattern against NADPH and a noncompetitive pattern against DXP. Fosmidomycin was an uncompetitive inhibitor against NADPH and gave a pattern representative of slow, tight-binding competitive inhibition against DXP. These results are consistent with an ordered mechanism where NADPH binds before DXP. PMID- 11772022 TI - Catalytic mapping of the vibriobactin biosynthetic enzyme VibF. AB - The iron-chelating catechol siderophore vibriobactin of the pathogenic Vibrio cholerae is assembled by a four-subunit, ten-domain nonribosomal peptide synthetase system, VibE, VibB, VibH, and VibF, using 2,3-dihydroxybenzoate and L threonine as precursors to two (dihydroxyphenyl)methyloxazolinyl groups in amide linkage on a norspermidine scaffold. We have utilized site-specific and domain deletion mutagenesis to map the heterocyclization and primary and secondary amine acylation activities of the six-domain (Cy1-Cy2-A-C1-PCP-C2) VibF subunit. We have found that Cy2 is capable of and limited to the condensation (amide bond formation) step of the three-step heterocyclization process, while Cy1 is capable of and limited to the final processing (cyclization/dehydration) steps to the completed heterocycle. Additionally, we have observed that the C2 domain functions in both N(9) (primary amine) acylation and N(5) (secondary amine) acylation of the (dihydroxybenzoyl)norspermidine substrate, leaving no catalytic role for the C1 domain, a conclusion confirmed with the formation of vibriobactin in a C1-deficient system. Thus VibF is an NRPS with two domains, Cy1 and Cy2, that perform a function otherwise performed by one and with one domain, C2, that performs a function otherwise performed by two. While C2 appeared to tolerate uncyclized threonine in place of the usual heterocycle in primary amine acylation, it refused this replacement in the corresponding donor substrate in secondary amine acylation. PMID- 11772023 TI - Soluble fusion proteins between single transmembrane photoreceptor guanylyl cyclases and their activators. AB - Among single-spanning transmembrane receptors (sTMRs), two guanylyl cyclase receptors, GC1 and GC2, are critically important during phototransduction in vertebrate retinal photoreceptor cells. Ca(2+)-free forms of guanylyl cyclase activating proteins (GCAPs) stimulate GCs intracellularly by a molecular mechanism that is not fully understood. To gain further insight into the mechanism of activation and specificity among these proteins, for the first time, several soluble and active truncated GCs and fusion proteins between intracellular domains of GCs and full-length GCAPs were generated. The GC activity of myristoylated GCAP--(437-1054)GC displayed typical [Ca(2+)] dependence, and was further enhanced by ATP and inhibited by guanylyl cyclase inhibitor protein (GCIP). The myristoyl group of GCAP1 appeared to be critical for the inhibition of GCs at high [Ca(2+)], even without membranes. In contrast, calmodulin (CaM)--(437-1054)GC1 fusion protein was inactive, but could be stimulated by exogenous GCAP1. In a series of experiments, we showed that the activation of GCs by linked GCAPs involved intra- and intermolecular mechanisms. The catalytically productive GCAP1--(437-1054)GC1 complex can dissociate, allowing binding and stimulation of the GC1 fusion protein by free GCAP1. This suggests that the intramolecular interactions within the fusion protein have low affinity and are mimicking the native system. We present evidence that the mechanism of GC activation by GCAPs involves a dimeric form of GCs, involves direct interaction between GCs and GCAPs, and does not require membrane components. Thus, fusion proteins may provide an important advance for further structural studies of photoreceptor GCs and other sTMRs with and without different forms of regulatory proteins. PMID- 11772024 TI - A GPR-protein interaction surface of Gi(alpha): implications for the mechanism of GDP-release inhibition. AB - Proteins containing G-protein regulatory (GPR) motifs represent a novel family of guanine nucleotide dissociation inhibitors (GDIs) for G(alpha) subunits from the Gi family. They selectively interact with the GDP-bound conformation of Gi(alpha) and transducin-alpha (Gt(alpha)), but not with Gs(alpha). A series of chimeric proteins between Gi(alpha)(1) and Gs(alpha) has been constructed to investigate GPR-contact sites on G(alpha) subunits and the mechanism of GPR-protein GDI activity. Analysis of the interaction of two GPR-proteins-AGS3GPR and Pcp2-with the chimeric G(alpha) subunits demonstrated that the GPR-Gi(alpha)(1) interface involves the Gi(alpha)(1) switch regions and Gi(alpha)(1)-144-151, a site within the helical domain. Residues within Gi(alpha)(1)-144-151 form conformation sensitive contacts with switch III, and may directly interact with a GPR-protein or form a GPR-binding surface jointly with switch III. The helical domain site is critical to the ability of GPR-proteins to act as GDIs. Our data suggest that a mechanism of the GDI activity of GPR-proteins is different from that of GDIs for monomeric GTPases and from the GDI-like activity of G(betagamma) subunits. The GPR-proteins are likely to block a GDP-escape route on G(alpha) subunits. PMID- 11772026 TI - The primary structure and the disulfide links of the bovine relaxin-like factor (RLF). AB - The relaxin-like factor (RLF), produced by the Leydig cells, is an essential link in the chain of events leading to the proper positioning of the testes during fetal development. The primary structure of RLF, as reported in the literature, is based solely upon cDNA sequences with chain lengths determined according to deduced processing sites and with relaxin-like cross-links. Biochemical characterization of bovine testicular RLF shows clearly that the endogenous hormone does consist of a 26 residue A chain and two forms of B chain, one containing 40 residues, the other 45. In addition, both B chains are 9 residues longer at the C terminus than the cDNA-deduced chain, and about 20% of the B chains have an additional 5 residue extension at the N terminus. Sequence analysis in combination with mass spectrometry and tryptic peptide mapping showed unambiguously that RLF is larger than previously assumed and that it has the relaxin-type disulfide bond distribution that makes it a bona fide member of the relaxin family of hormones. PMID- 11772025 TI - Probing for preferential interactions among sphingolipids in bilayer vesicles using the glycolipid transfer protein. AB - We have investigated the intervesicular transfer of galactosylceramide between unilamellar bilayer vesicles composed of differing sphingomyelin and phosphatidylcholine molar ratios. To monitor glycolipid transfer from donor to acceptor vesicles, we used a fluorescence resonance energy transfer assay involving anthrylvinyl-labeled galactosylceramide (AV-GalCer) and perylenoyl labeled triglyceride. The transfer was mediated by glycolipid transfer protein (GLTP), purified from bovine brain and specific for glycolipids. The initial transfer rate and the total accessible pool of glycolipid in the donor vesicles were both measured. An increase in the sphingomyelin content of 1-palmitoyl-2 oleoyl phosphatidylcholine (POPC) vesicles decreased the transfer rate in a nonlinear fashion. Decreased transfer rates were clearly evident at sphingomyelin mole fractions of 0.22 or higher. The pool of AV-GalCer available for GLTP mediated transfer also was smaller in vesicles containing high sphingomyelin content. In contrast, AV-GalCer was more readily transferred from vesicles composed of POPC and different disaturated phosphatidylcholines. Our results show that GLTP acts as a sensitive probe for detecting interactions of glycosphingolipids with neighboring lipids and that the lateral mixing of glycolipids is probably affected by the matrix lipid composition. The compositionally driven changes in lipid interactions, sensed by GLTP, occur in membranes that are either macroscopically fluid-phase or gel/fluid-phase mixtures. Gaining insights into how changes in membrane sphingolipid composition alter accessibility to soluble proteins with affinity for membrane glycolipids is likely to help increase our understanding of how sphingolipid-enriched microdomains (i.e., "rafts" and caveolae) are formed and maintained in cells. PMID- 11772028 TI - Preparation of irreversibly sickled cell beta-actin from normal red blood cell beta-actin. AB - We have previously demonstrated that an oxidative change, the formation of a disulfide bridge between two cysteine residues, in the membrane protein beta actin is primarily responsible for locking the irreversibly sickled red blood cells (ISCs) of sickle cell anemic patients into the sickle shape. To support studies on biological and chemical characterization of the oxidized beta-actin and pharmacological research toward the reversal of the oxidation, we attempted to prepare oxidized beta-actin from normal red blood cell (RBC) beta-actin by a chemical reaction, expecting a product equivalent to that found in ISCs. 5,5' Dithiobis(2-nitrobenzoic acid) (DTNB, or Ellman's reagent) was used for the oxidation. We proved the absence of accessible sulfhydryl groups in the oxidized product using liquid chromatography (LC) with both UV and fluorescence detection. Polymerization assays indicated that the chemically produced ISC actin demonstrated the same kinetics as ISC actin obtained from patients with sickle cell disease. The effect of the oxidation could be reversed by the use of the reducing agent tris(carboxyethyl)phosphine (TCEP). PMID- 11772027 TI - Evidence that clusterin has discrete chaperone and ligand binding sites. AB - Clusterin is the first identified extracellular mammalian chaperone and binds to a wide variety of partly unfolded, stressed proteins.Clusterin also binds to many different unstressed ligands including the cell surface receptor low-density lipoprotein receptor-related protein-2 (LRP-2). It is unknown whether clusterin binds to all of these many ligands via one or more binding sites. Furthermore, the region(s) of clusterin involved in these many binding interactions remain(s) to be identified. As part of an investigation of these issues, we expressed recombinant human clusterin in the yeast Pichia pastoris. The resultant protein had variable proteolytic truncations of the C-terminal region of the alpha-chain and the N-terminal region of the beta-chain. We compared the chaperone and ligand binding activities of this recombinant product with those of clusterin purified from human serum. We also tested whether the binding of clusterin to ligands could be inhibited by competitive binding with other clusterin ligands or by anti clusterin monoclonal antibodies. Collectively, our results indicate that (i) clusterin has three independent classes of binding sites for LRP-2, stressed proteins, and unstressed ligands, respectively, and (ii) the binding sites for LRP-2 and stressed proteins are likely to be in parts of the molecule other than the C-terminal region of the alpha-chain or the N-terminal region of the beta chain. It has been suggested that, in vivo, clusterin binds to toxic molecules in the extracellular environment and carries these to cells expressing LRP-2 for uptake and degradation. This hypothesis is supported by our demonstration that clusterin has discrete binding sites for LRP-2 and other (potentially toxic) molecules. PMID- 11772029 TI - The alphaA-crystallin R116C mutant has a higher affinity for forming heteroaggregates with alphaB-crystallin. AB - An autosomal dominant congenital cataract in humans is associated with mutation of Arg-116 to Cys in alphaA-crystallin (alphaA-R116C). The chaperone activity and biophysical properties of reconstituted alpha-crystallin from different proportions of wild-type alphaB-crystallin (alphaB-wt) and alphaA-R116C crystallin were studied by gel permeation chromatography, SDS-polyacrylamide gel electrophoresis, and fluorescence and circular dichroism spectroscopy and compared with those of reconstituted alpha-crystallin from alphaB-wt and wild type alphaA-crystallin (alphaA-wt). The reconstituted alpha-crystallin containing alphaA-R116C and alphaB-wt had a higher molecular mass, a higher thermal sensitivity to exposition of Trp side chains, fewer available hydrophobic surfaces, and lower chaperone activity than the alpha-crystallin containing alphaA-wt and alphaB-wt. The secondary structure exhibited very small changes, whereas the tertiary structure was distinctly different for alpha-crystallin formed from alphaA-R116C and alphaB-wt. Most importantly, subunit exchange studies by fluorescence resonance energy transfer showed that alphaA-R116C forms heteroaggregates faster than alphaA-wt with alphaB-wt, and the reconstituted alpha-crystallins were true heteroaggregates of two interacting subunits. These findings suggest that the molecular basis for the congenital cataract with the alphaA-R116C mutation is the formation of highly oligomerized heteroaggregates of alpha-crystallin with modified structure. However, contrary to the earlier conclusions based on the studies of homoaggregates, the loss in chaperone activity of the heteroaggregates having alphaA-R116C does not appear to be large enough to become the main factor in initiating cataract development in the affected individuals. PMID- 11772030 TI - Temperature dependence of the epidermal growth factor receptor signaling network can be accounted for by a kinetic model. AB - Stimulation of isolated hepatocytes with epidermal growth factor (EGF) causes rapid tyrosine phosphorylation of the EGF receptor (EGFR) and adapter/target proteins, which was monitored with 1 and 2 s resolution at 37, 20, and 4 degrees C. The temporal responses detected for multiple signaling proteins involve both transient and sustained phosphorylation patterns, which change dramatically at low temperatures. To account quantitatively for complex responses, we employed a mechanistic kinetic model of the EGFR pathway, formulated in molecular terms as cascades of protein interactions and phosphorylation and dephosphorylation reactions. Assuming differential temperature dependencies for different reaction groups, such as SH2 and PTB domain-mediated interactions, the EGFR kinase, and the phosphatases, good quantitative agreement was obtained between computer simulated and measured responses. The kinetic model demonstrates that, for each protein-protein interaction, the dissociation rate constant, k(off), strongly decreases at low temperatures, whereas this decline may or may not be accompanied by a large decrease in the k(on) value. Temperature-induced changes in the maximal activities of the reactions catalyzed by the EGFR kinase were moderate, compared to such changes in the V(max) of the phosphatases. However, strong changes in both the V(max) and K(m) for phosphatases resulted in moderate changes in the V(max)/K(m) ratio, comparable to the corresponding changes in EGFR kinase activity, with a single exception for the receptor phosphatase at 4 degrees C. The model suggests a significant decrease in the rates of the EGF receptor dimerization and its dephosphorylation at 4 degrees C, which can be related to the phase transition in the membrane lipids. A combination of high-resolution experimental monitoring and molecular level kinetic modeling made it possible to quantitatively account for the temperature dependence of the integrative signaling responses. PMID- 11772031 TI - Equilibrium collapse and the kinetic 'foldability' of proteins. AB - An important element of protein folding theory has been the identification of equilibrium parameters that might uniquely distinguish rapidly folding polypeptide sequences from those that fold slowly. One such parameter, termed sigma, is a dimensionless, equilibrium measure of the coincidence of chain compaction and folding that is predicted to be an important determinant of relative folding kinetics. To test this prediction and improve our understanding of the putative relationship between nonspecific compaction of the unfolded state and protein folding kinetics, we have used small-angle X-ray scattering and circular dichroism spectroscopy to measure the sigma of five well-characterized proteins. Consistent with theoretical predictions, we find that near-perfect coincidence of the unfolded state contraction and folding (sigma approximately 0) is associated with the rapid kinetics of these naturally occurring proteins. We do not, however, observe any significant correlation between sigma and either the relative folding rates of these proteins or the presence or absence of well populated kinetic intermediates. Thus, while sigma approximately 0 may be a necessary condition to ensure rapid folding, differences in sigma do not account for the wide range of rates and mechanisms with which naturally occurring proteins fold. PMID- 11772032 TI - Does beta-lactoglobulin denaturation occur via an intermediate state? AB - The denaturation of beta-lactoglobulin (BLG) in the presence of urea and GuHCl has been investigated at different pH values with various spectroscopic techniques. The equilibrium denaturation free energy values, obtained by linearly extrapolating the data to vanishing denaturant (DeltaG(D)(H2O)), are compared and discussed. The fit of the spectroscopic data monitoring the denaturation of BLG has been approached, at first, with a two-state model that describes the protein transition from the folded state (at each pH and in the absence of denaturant) to the denatured state, but in particular, along the GuHCl denaturation pathway some evidence is found of the presence of an intermediate state. Time-resolved fluorescence experiments performed on the BLG-ANS (1-anilino-8 naphthalenesulfonate) complex help to understand the results. Fluorescence polarization anisotropy (FPA) measurements accompanying the denaturation process show the presence of a fast rotational diffusion of the ANS probe, and the data are interpreted in terms of local fluctuations of a still structured tract of the denatured protein where the probe is bound. PMID- 11772033 TI - Heterogeneity in serpin-protease complexes as demonstrated by differences in the mechanism of complex breakdown. AB - Serpins trap their target proteases in the form of an acyl-enzyme complex. The trap is kinetic, however, and thus serpin-protease complexes ultimately break down, releasing a cleaved inactive serpin and an active protease. The rates of this deacylation process vary greatly depending on the serpin-protease pair with half-lives ranging from minutes to months. The reasons for the diversity in breakdown rates are not clearly understood. In the current study, pH and solvent isotope effects were utilized to probe the mechanism of breakdown for an extremely stable complex and several unstable complexes. Two different patterns for the pH dependence of k(bkdn), the first-order rate constant of breakdown, were found. The stable complex, which breaks down at neutral pH with a half-life of approximately 2 weeks, exhibited a pH-k(bkdn) profile consistent with solvent hydroxide ion mediated ester hydrolysis. There was no evidence for the participation of the catalytic machinery in the breakdown of this complex, suggesting extensive distortion of the active site. The unstable complexes, which break down with half-lives ranging from minutes to hours, exhibited a bell-shaped pH profile for k(bkdn), typical of the pH-rate profiles of free serine proteases. In the low to neutral pH range k(bkdn) increased with increasing pH in a manner characteristic of His57-mediated catalysis. In the alkaline pH range a decrease in k(bkdn) was observed, consistent with the titration of the Ile16-Asp194 salt bridge (chymotrypsinogen numbering). The alkaline pH dependence was not exhibited in pH-rate profiles of free or substrate-bound HNE, indicating that the salt bridge was significantly destabilized in the complexed protease. These results indicate that breakdown is catalytically mediated in the unstable complexes although, most likely, the protease is not in its native conformation and the catalytic machinery functions inefficiently. However, a mechanism in which breakdown is determined by the equilibrium between distorted and undistorted forms of the complexed protease cannot be completely dismissed. Overall, the results of this study suggest that the protease structure in unstable complexes is distorted to a lesser extent than in stable complexes. PMID- 11772034 TI - DNA hydrolysis and oxidative cleavage by metal-binding peptides tethered to rhodium intercalators. AB - With the goal of developing artificial nucleases for DNA hydrolysis, metal coordinating peptides have been tethered to a DNA-intercalating rhodium complex to deliver metal ions to the sugar-phosphate backbone. The intercalator, [Rh(phi)(2)bpy']Cl(3) [phi = 9,10-phenanthrenequinone diimine; bpy' = 4-(butyric acid)-4'-methyl-2,2'-bipyridine], provides DNA binding affinity, and a metal binding peptide contributes reactivity. This strategy for DNA hydrolysis is a general one, and zinc(II)-promoted cleavage has been demonstrated for two widely different tethered metallopeptides. An intercalator coupled with a de novo designed alpha helix containing two histidine residues has been demonstrated to cleave both supercoiled plasmid and linear DNA substrates. Mutation of this peptide confirms that the two histidine residues are essential for Zn(2+) binding and cleavage. Zinc(II)-promoted cleavage of supercoiled plasmid has also been demonstrated with an intercalator-peptide conjugate containing acidic residues and modeled after the active site of the BamHI endonuclease. Other redox-active metals, such as copper, have been delivered to DNA with our intercalator-peptide conjugates to effect oxidative chemistry. Copper cleavage experiments and photocleavage experiments with [Rh(phi)(2)bpy'](3+) complement the hydrolysis studies and provide structural information about the interactions between the tethered metallopeptides and DNA. Variation of the rhodium intercalator was also explored, but with a mismatch-specific intercalator, no site-specific hydrolysis was found. These experiments, in which the peptide, the metal cation, and the intercalator components of the conjugate are each varied, illustrate some of the issues involved in creating an artificial nuclease with DNA intercalators and metallopeptides. PMID- 11772035 TI - Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation. AB - DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine to-pyrimidine triplex conversion depends on the chemical nature of the triplex forming strands and the stability of the corresponding triplexes. PMID- 11772036 TI - Characteristics and mechanism of formation of peroxide-induced heme to protein cross-linking in myoglobin. AB - At acidic pH values heme-protein cross-linked myoglobin (Mb-H) forms as a product of a peroxide-induced ferric-ferryl redox cycle. There is evidence that this molecule acts as a marker for heme-protein-induced oxidative stress in vivo and may exacerbate the severity of oxidative damage due to its enhanced prooxidant and pseudoperoxidatic activities. Therefore, an understanding of its properties and mechanism of formation may be important in understanding the association between heme-proteins and oxidative stress. Although the mechanism of formation of heme-protein cross-linked myoglobin is thought to involve a protein radical (possibly a tyrosine) and the ferryl heme, we show that this hypothesis needs revising. We provide evidence that in addition to a protein-based radical the protonated form of the oxoferryl heme, known to be highly reactive and radical like in nature, is required to initiate cross-linking. This revised mechanism involves radical/radical termination rather than attack of a single radical onto the porphyrin ring. This proposal better explains the pH dependence of cross linking and may, in part, explain the therapeutic effectiveness of increasing the pH on myoglobin-induced oxidative stress, e.g., therapy for rhabdomyolysis associated renal dysfunction. PMID- 11772037 TI - UV resonance Raman study of beta93-modified hemoglobin A: chemical modifier specific effects and added influences of attached poly(ethylene glycol) chains. AB - The reactive sulfhydryl group on Cys beta93 in human adult hemoglobin (HbA) has been the focus of many studies because of its importance both as a site for synthetic manipulation and as a possible binding site for nitric oxide (NO) in vivo. Despite the interest in this site and the known functional alterations associated with manipulation of this site, there is still considerable uncertainty as to the conformational basis for these effects. UV resonance Raman (UVRR) spectroscopy is used in this study to evaluate the conformational consequences of chemically modifying the Cys beta93 sulfhydryl group of both the deoxy and CO-saturated derivatives of HbA using different maleimide and mixed disulfide reagents. Included among the maleimide reagents are NEM (n ethylmaleimide) and several poly(ethylene glycol) (PEG)-linked maleimides. The PEG-based reagents include both different sizes of PEG chains (PEG2000, -5000, and -20000) and different linkers between the PEG and the maleimide. Thus, the effect on the conformation of both linker chemistry and PEG size is evaluated. The spectroscopic results reveal minimal perturbation of the global structure of deoxyHbA for the mixed disulfide modification. In contrast, maleimide-based modifications of HbA perturb the deoxy T state of HbA by "loosening" the contacts associated with the switch region of the T state alpha(1)beta(2) interface but do not modify the hinge region of this interface. When the NEM-modified HbA is also subjected to enzymatic treatment to remove the C-terminal Arg alpha141 (yielding NESdes-ArgHb), the resulting deoxy derivative exhibits the spectroscopic features associated with a deoxy R state species. All of the CO-saturated derivatives exhibit spectra that are characteristic of the fully liganded R structure. The deoxy and CO derivatives of HbA that have been decorated on the surface with large PEG chains linked to the maleimide-modified sulfhydryl through a short linker group all show a general intensity enhancement of the tyrosine and tryptophan bands in the UVRR spectrum. It is proposed that this effect arises from the osmotic impact of a large, close PEG molecule enveloping the surface of the protein. PMID- 11772038 TI - High selectivity of human tissue transglutaminase for immunoactive gliadin peptides: implications for celiac sprue. AB - Celiac Sprue is an HLA DQ2 (or DQ8)-associated autoimmune disorder of the human small intestine that is induced by dietary exposure to wheat gliadin and related proteins from barley, rye, and possibly other food grains. Recently, tissue transglutaminase (tTGase)-catalyzed deamidation of gliadin peptides has been shown to increase their potency for activating patient-derived, gliadin-specific T cells, suggesting that tTGase plays a causative role in the onset of an inflammatory response to toxic food grains. To dissect the molecular recognition features of tTGase for gluten derived peptides, the regioselectivity and steady state kinetics of tTGase-catalyzed deamidation of known immunogenic peptides were investigated. The specificity of recombinant human tTGase for all immunogenic peptides tested was comparable to and, in some cases, appreciably higher than the specificity for its natural substrate. Although each peptide was glutamine-rich, tTGase exhibited a high degree of regioselectivity for a particular glutamine residue in each peptide. This selectivity correlated well with Q --> E substitutions that have earlier been shown to enhance the immunogenicity of the corresponding gliadin peptides. The specificity of tTGase toward homologues of PQPQLPY, a sequence motif found in immunodominant gliadin peptides, was analyzed in detail. Remarkably, the primary amino acid sequences of wheat-, rye-, and barley-derived proteins included many single-residue variants of this sequence that were high-affinity substrates of tTGase, whereas the closest homologues of this sequence found in rice, corn, or oat proteins were much poorer substrates of tTGase. (Rice, corn, and oats are nontoxic ingredients of the Celiac diet.) No consensus sequence for a high-affinity substrate of tTGase could be derived from our data, suggesting that the secondary structures of these food-grain peptides were important in their recognition by tTGase. Finally, under steady-state turnover conditions, a significant fraction of the tTGase active site was covalently bound to a representative high-affinity immunogenic gliadin peptide, suggesting a common mechanism by which cells responsible for immune surveillance of the intestinal tract recognize and generate an antibody response against both gliadin and tTGase. In addition to providing a quantitative framework for understanding the role of tTGase in Celiac Sprue, our results lay the groundwork for the design of small molecule mimetics of gliadin peptides as selective inhibitors of tTGase. PMID- 11772039 TI - Insertional inactivation of the menG gene, encoding 2-phytyl-1,4-naphthoquinone methyltransferase of Synechocystis sp. PCC 6803, results in the incorporation of 2-phytyl-1,4-naphthoquinone into the A(1) site and alteration of the equilibrium constant between A(1) and F(X) in photosystem I. AB - A gene encoding a methyltransferase (menG) was identified in Synechocystis sp. PCC 6803 as responsible for transferring the methyl group to 2-phytyl-1,4 naphthoquinone in the biosynthetic pathway of phylloquinone, the secondary electron acceptor in photosystem I (PS I). Mass spectrometric measurements showed that targeted inactivation of the menG gene prevented the methylation step in the synthesis of phylloquinone and led to the accumulation of 2-phytyl-1,4 naphthoquinone in PS I. Growth rates of the wild-type and the menG mutant strains under photoautotrophic and photomixotrophic conditions were virtually identical. The chlorophyll a content of the menG mutant strain was similar to that of wild type when the cells were grown at a light intensity of 50 microE m(-2) s(-1) but was slightly lower when grown at 300 microE m(-2) s(-1). Chlorophyll fluorescence emission measurements at 77 K showed a larger increase in the ratio of PS II to PS I in the menG mutant strain relative to the wild type as the light intensity was elevated from 50 to 300 microE m(-2) s(-1). CW EPR studies at 34 GHz and transient EPR studies at multiple frequencies showed that the quinone radical in the menG mutant has a similar overall line width as that for the wild type, but consistent with the presence of an aromatic proton at ring position 2, the pattern of hyperfine splittings showed two lines in the low-field region. The spin polarization pattern indicated that 2-phytyl-1,4-naphthoquinone is in the same orientation as phylloquinone, and out-of-phase, spin-echo modulation spectroscopy shows the same P700(+) to Q(-) center-to-center distance as in wild type PS I. Transient EPR studies indicated that the lifetime for forward electron transfer from Q(-) to F(X) is slowed from 290 ns in the wild type to 600 ns in the menG mutant. The redox potential of 2-phytyl-1,4-naphthoquinone is estimated to be 50 to 60 mV more oxidizing than phylloquinone in the A(1) site, which translates to a lowering of the equilibrium constant between Q(-)/Q and F(X)( )/F(X) by a factor of ca. 10. The lifetime of the P700(+) [F(A)/F(B)](-) backreaction decreased from 80 ms in the wild type to 20 ms in the menG mutant strain and is evidence for a thermally activated, uphill electron transfer through the quinone rather than a direct charge recombination between [F(A)/F(B)](-) and P700(+). PMID- 11772040 TI - Transposable dual reporters for studying the structure-function relationships in membrane proteins: permissive sites in R. prowazekii ATP/ADP translocase. AB - A new approach to studying membrane topology and permissive sites in membrane proteins expressed in Escherichia coli is described. The method is based on in vitro transposition of mini-Tn5 derivatives bearing dual pho-lac reporters [Alexeyev, M. F., and Winkler, H. H. (1999) J. Mol. Biol. 285, 1503-1513]. Two mini-Tn5 transposons, Tnpholac1 and Tnpholac2, were designed in such a way that their insertions can be converted either by restriction-ligation or by in vivo Cre-lox recombination into either sandwich reporter fusions or short amino acid (aa) tags (25 or 42 aa long). A set of 48 unique insertions in the gene coding for the Rickettsia prowazekii ATP/ADP translocase (Tlc) was generated using Tnpholac2. The topological information generated by these insertions was found in to be in good agreement with the existing topological model. Subsequently, these insertions were converted into both 25 and 42 aa tags, and the activity of the resulting mutants was determined. Also, site-directed mutagenesis was used to construct insertions in the loops, where no transposon hops were discovered. Of 13 extramembrane domains in Tlc, only 3 (loops 7, 10, and 13) were found to be permissive, which is in marked contrast to previous observations in the E. coli lactose permease (LacY), where most insertions in extramembrane domains were demonstrated to be permissive. The permissiveness of the insertion after I368 in TM IX lead us to reconsider the boundaries for this TM by placing I368 on the interface between TM IX and loop 10. Interestingly, the 25 aa insertions consistently have 2-fold higher activity than the corresponding 42 aa insertions, which is also in contrast with observations made on LacY. Finally, in this study we report, for the first time, the frequency of 10 base pair target duplications generated by in vitro Tn5 transposition. PMID- 11772041 TI - 15N kinetic isotope effects on uncatalyzed and enzymatic deamination of cytidine. AB - 15N isotope effects and solvent deuterium isotope effects have been measured for the hydrolytic deamination of cytidine catalyzed by Escherichia coli cytidine deaminase and for the uncatalyzed reaction proceeding spontaneously in neutral solution at elevated temperatures. The primary (15)(V/K) arising from the exocyclic amino group for wild-type cytidine deaminase acting on its natural substrate, cytidine, is 1.0109 (in H(2)O, pH 7.3), 1.0123 (in H(2)O, pH 4.2), and 1.0086 (in D(2)O, pD 7.3). Increasing solvent D(2)O content has no substantial effect on k(cat) but enhances k(cat)/K(m), with a proton inventory showing that the fractionation factors of at least two protons increase markedly during the reaction. Mutant cytidine deaminases with reduced catalytic activity show more pronounced (15)N isotope effects of 1.0124 (Glu91Ala), 1.0134 (His102Ala), and 1.0158 (His102Asn) at pH 7.3 in H(2)O, as expected for processes in which the chemical transformation of the substrate becomes more rate determining. The isotope effect of mutant His102Asn is 1.033 after correcting for protonation of the -NH(2) group, and represents the intrinsic isotope effect on C-N bond cleavage. This result allows an estimation of the forward commitment of the reaction with the wild-type enzyme. The observed (15)N kinetic isotope effect of the pyrimidine N-3, for wild-type cytidine deaminase acting on cytidine, is 0.9879, which is consistent with protonation and rehybidization of N-3 with hydroxide ion attack on the adjacent carbon to create a tetrahedral intermediate. These results show that enzymatic deamination of cytidine proceeds stepwise through a tetrahedral intermediate with ammonia elimination as the major rate determining step. The primary (15)N isotope effects observed for the uncatalyzed reaction at pH 7 (1.0021) and pH 12.5 (1.0034) were found to be insensitive to changing temperatures between 100 and 185 degrees C. These results show that the uncatalyzed and the enzymatic deaminations of cytidine proceed by similar mechanisms, although the commitment to C-N bond breaking is greater for the spontaneous reaction. PMID- 11772042 TI - Isolation and characterization of rhodanese intermediates during thermal inactivation and their implications for the mechanism of protein aggregation. AB - The initial steps of heat-induced inactivation and aggregation of the enzyme rhodanese have been studied and found to involve the early formation of modified but catalytically active conformations. These intermediates readily form active dimers or small oligomers, as evident from there being only a small increase in light scattering and an increase in fluorescence energy homotransfer from rhodanese labeled with fluorescein. These species are probably not the domain unfolded form, as they show activity and increased protection of hydrophobic surfaces. Cross-linking with glutaraldehyde and fractionation by gel filtration show the predominant formation of dimer during heat incubation. Comparison between the rates of aggregate formation at 50 degrees C after preincubation at 25 or 40 degrees C gives evidence of product-precursor relationships, and it shows that these dimeric or small oligomeric species are the basis of the irreversible aggregation. The thermally induced species is recognized by and binds to the chaperonin GroEL. The unfoldase activity of GroEL subsequently unfolds rhodanese to produce an inactive conformation and forms a stable, reactivable complex. The release of 80% active rhodanese upon addition of GroES and ATP indicates that the thermal incubation induces an alteration in conformation, rather than any covalent modification, which would lead to formation of irreversibly inactive species. Once oligomeric species are formed from the intermediates, GroEL cannot recognize them. Based on these observations, a model is proposed for rhodanese aggregation that can explain the paradoxical effect in which rhodanese aggregation is reduced at higher protein concentration. PMID- 11772045 TI - Strong electron-acceptor methylviologen dications confined in a 2D inorganic host: synthesis, structural characterization, charge transport and electrochemical properties of (MV)(0.25)V(2)O(5). AB - The reaction of methylviologen iodide with crystalline V2O5 in the molar ratio of 1 to 3.8 at 100 degrees C in water led to the formation of (MV)0.25V2O5 in quantitative yield. The structure of this organic-inorganic multilayered hybrid compound was determined by single-crystal X-ray crystallography. Strong van der Waals interactions were found between the electron-deficient aromatic organic molecules and the inorganic layers. In the solid state, the compound is a semiconductor due to small polaron hopping and shows novel reversible alkali-ion intercalation/deintercalation via electrochemistry. PMID- 11772046 TI - Simple Cu(I) complexes with unprecedented excited-state lifetimes. AB - This report describes new, readily accessible copper(I) complexes that can exhibit unusually long-lived, high quantum yield emissions in fluid solution. The complexes are of the form [Cu(NN)(POP)]+ where NN denotes 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,9-di-n-butyl-1,10 phenanthroline (dbp) and POP denotes bis[2-(diphenylphosphino)phenyl] ether. Modes of characterization include X-ray crystallography and cyclic voltammetry. The complexes each have a pseudotetrahedral coordination geometry and a Cu(II)/Cu(I) potential upward of +1.2 V vs Ag/AgCl. In room-temperature dichloromethane solution, charge-transfer excited states of the dmp and dbp derivatives exhibit respective emission quantum yields of 0.15 and 0.16 and corresponding excited-state lifetimes of 14.3 and 16.1 mus, respectively. Despite the fact that coordinating solvents usually quench charge-transfer emission from copper systems, the photoexcited dmp (dbp) complex retains a lifetime of 2.4 mus (5.4 mus) in methanol. PMID- 11772047 TI - Laterally stabilized complexes of DNA with linear reducible polycations: strategy for triggered intracellular activation of DNA delivery vectors. AB - Target-specific DNA delivery requires vectors that combine stability in the biological milieu, receptor-mediated uptake into target cells, and intracellular activation to mediate transgene expression. This is achieved here using polymer coated vectors based on plasmid DNA complexed with a reductively degradable polycation (RPC), designed for intercellular degradation. The RPC were prepared by oxidation of the terminal cysteinyl thiol groups of Cys(Lys)10Cys. The complexes were coated and surface-cross-linked using multivalent reactive copolymers of N-(2-hydroxypropyl)methacrylamide (PHPMA), providing a unique combination of steric and reversible lateral stabilization, known to promote extended circulation in the bloodstream. Coated complexes containing RPC exhibited lateral stabilization that was reversible by treatment with 2.5 mM dithiothreitol, releasing free DNA after incubation with a polyanion. In contrast, coated complexes containing nonreducible poly(l-lysine) (PLL) were not destabilized by reduction. The biological usefulness of this trigger mechanism was examined by measuring transfection activity in human retinoblast 911 cells of coated complexes, based on PLL or RPC, targeted to cell surface receptors by covalent linkage of basic fibroblast growth factor. The levels of transgene expression observed for RPC-based targeted vectors indicated efficient intracellular activation, authenticating the concept that lateral stabilization introduced by surface coating with PHPMA can be reversed by intracellular reduction. PMID- 11772049 TI - Catalytic asymmetric intramolecular aminopalladation: enantioselective synthesis of vinyl-substituted 2-oxazolidinones, 2-imidazolidinones, and 2-pyrrolidinones. AB - A new catalytic asymmetric synthesis of five-membered nitrogen heterocycles is reported. This synthesis employs ferrocenyloxazoline palladacycles (FOP trifluoroacetate catalysts) 2 and 4 and proceeds by a catalytic cycle involving Pd(II) intermediates. For example, prochiral (Z)-4-acetoxy-2-buten-1-ols are condensed with an arylsulfonyl isocyanate and the derived allylic N arylsulfonylcarbamates cyclize in situ upon addition of 0.5-5 mol % of 2 or 4 to form 4-vinyloxazolidin-2-ones 6, 13, and 15 in high yield and 89-99% ee. The related 2-pyrrolidinone 19 and 2-imidazolidinone 18 are prepared in similar fashion. Pyrrolidinone 19 can be converted in two steps to the unnatural enantiomer of the GABA inhibitor vigabatrin 20. PMID- 11772048 TI - Discovery of exceptionally efficient catalysts for solvent-free enantioselective hetero-Diels-Alder reaction. AB - Combinatorial coordination chemistry strategy combined with high-throughput screening techniques has been successfully applied to engineering practical enantioselective catalysts for asymmetric hetero-Diels-Alder reaction. The reaction of Danishefsky's diene with a variety of aldehydes can be carried out with 0.1-0.005 mol % of H4-BINOL/Ti/H4-BINOL or H4-BINOL/Ti/H8-BINOL catalysts at room temperature under solvent- and MS-free conditions to afford dihydropyrone derivatives with up to quantitative yield and 99.8% ee. PMID- 11772050 TI - Self-terminating, oxidative radical cyclizations: a novel reaction of acyloxyl radicals. AB - Acyloxyl radicals RC(O)O* (with R = alkyl, aryl) could be trapped through addition to cyclic and open-chain alkynes, where they were found to act as a donor of oxygen atoms. Mechanistically, this radical oxygenation proceeded through a transannular or intramolecular, respectively, radical cyclization cascade, which was finally terminated by release of an acyl radical RC*(O). The reaction led to stereoselective formation of cyclized products, which contained a carbonyl group at the former site of the alkyne triple bond. PMID- 11772051 TI - Synthesis and characterization of a disulfide-linked c(5)-symmetric [5]carceplex. AB - The synthesis and characterization of the first disulfide-linked and C5-symmetric carceplex.(guests)2 using the recently described [5]cavitands as building blocks is reported. The solution behavior of the new carceplexes was explored by 1D NOSEY (EXSY) experiments. The disulfides have unusually high energy barriers to interconversion due to their cooperativity. The guests (2 DMF or 2 DMA) reside in an unusual orientation in parallel planes that are perpendicular to the principal axis of the host. PMID- 11772052 TI - Design of three-dimensional, millimeter-scale models for molecular folding. AB - This communication describes the fabrication of three-dimensional structures of organic polymers using principles of design inspired by protein folding. The structures consist of rigid polyhedral components with dimensions of a few millimeters ("microdomains"), representing alpha-helical and beta-sheet secondary structures, connected with flexible linkers representing loops or turns. These structures were fabricated from polyurethane using photolithographic and soft lithographic techniques. The surfaces of the microdomains were patterned into hydrophobic and hydrophilic regions, and a hydrophobic photocurable liquid (serving both as lubricant and adhesive) was selectively precipitated onto the hydrophobic areas. The unfolded structures were suspended in water and agitated by tumbling. Self-assembly occurred through coalescence of the thin films of hydrophobic liquid, and was caused by minimization of the free energy of the interface between the liquid adhesive and the water. The self-assembled structures were locked in place by curing the adhesive with UV light. These results demonstrate the use of concepts abstracted from the study of proteins including attractive hydrophobic interactions, shape complementarity, and conformational constraint-in the self-assembly of complex, three-dimensional structures on the millimeter scale. PMID- 11772053 TI - Didehydrogeranylgeranyl (Delta Delta GG): a fluorescent probe for protein prenylation. AB - The first intrinsically fluorescent analog of geranylgeraniol, (2E,6E,8E,10E,12E,14E)-geranylgeraniol (all-trans-DeltaDeltaGGOH.1) has been synthesized stereoselectively and shown to substitute for the geranylgeranyl (GG) moiety in prenyl transferase reactions and in protein-ligand binding assays. All trans-DeltaDeltaGGOH 1 showed blue fluorescence in methanol, with lambdaex = 310 nm and lambdaem = 410 nm (epsilon310 = 2.4 x 104 M-1 cm-1), but was only weakly fluorescent in aqueous solution. The prenyl transferase efficiency for DeltaDeltaGGPP 2 as a substrate for yeast protein geranylgeranyl transferase (PGGTase-I) was 60% relative to that for GGPP. The binding of DeltaDeltaGG AcCysMe 3 to the recombinant Rho GTPase dissociation inhibitor (RhoGDI) had a KD of 15.1 +/- 1.2 muM, 6-fold lower than the affinity of GG-AcCysMe. Thus, the DeltaDeltaGG moiety is a novel fluorophore suitable for studying the interaction and subcellular localization of prenylated small GTPase proteins in signaling complexes. PMID- 11772054 TI - Large third-order optical nonlinearity of self-assembled porphyrin oligomers. AB - Third-order nonlinear optical properties of two series of self-assembled porphyrin wires, one being terminated by zinc porphyrin and the other by free base porphyrin, were measured by femtosecond time-resolved optical Kerr effect. The hyperpolarizability values of the latter series were extremely large ranging from 10-30 to 10-29 esu, 10 times larger than the former. The behavior is accounted for by the contribution of terminal free base porphyrin to enhance the molecular polarization by acceptor nature toward central metalloporphyrin array. PMID- 11772055 TI - Internal derivatization of oligonucleotides with selenium for X-ray crystallography using MAD. AB - We have developed a route for the synthesis of 2'-selenium uridine analogues and oligonucleotides containing selenium labels, and have demonstrated for the first time a new strategy to covalently derivatize nucleotides with selenium for phase and structure determination in X-ray crystallography. PMID- 11772056 TI - Redox thermodynamics of the Fe(3+)/Fe(2+) couple in horseradish peroxidase and its cyanide complex. AB - The thermodynamics of Fe3+ to Fe2+ reduction for the five-coordinate high-spin native form of horseradish peroxidase and for its six-coordinate low-spin cyanide adduct have been determined from variable-temperature UV-vis spectroelectrochemical experiments. In both cases, the DeltaH degrees 'rc and DeltaS degrees 'rc values are positive. Hence, the negative reduction potentials turn out to be the result of two opposing and partially compensating contributions: a large enthalpic term, which is the determinant of the negative E degrees ' values for both species, and a smaller, yet relevant, entropic contribution. The decrease in E degrees ' of the Fe3+/Fe2+ couple on cyanide binding turns out to be a fully entropic effect, unequivocally demonstrating the importance of entropic effects in determining the E degrees ' values of redox metal centers. PMID- 11772057 TI - Ruthenium-catalyzed cycloaddition of 1,6-diynes with isothiocyanates and carbon disulfide: first transition-metal catalyzed [2 + 2 + 2] cocyclotrimerization involving C=S double bond. AB - In the presence of 10 mol % Cp*Ru(cod)Cl, 1,6-diynes with a tertiary center at 4 position reacted with various isothiocyanates at their C=S double bond to afford bicyclic (2H)-thiopyranimines in 35-88% yields. The (2H)-thiopyran structure was unequivocally determined by X-ray analysis. The cycloaddition of carbon disulfide with a diyne similarly gave the expected bicyclic dithiopyrone in 50% yield. PMID- 11772058 TI - Reduction of a "cation pool": a new approach to radical mediated C--C bond formation. AB - Carbocations, carbon radicals, and carbanions are important reactive carbon intermediates in organic chemistry, and their interconversions can be carried out by redox processes. Although, such relationships have been well recognized, experimental work has been limited to analytical studies on highly stabilized intermediates. In this study such interconversions were examined using electrochemical reduction of "cation pools". Acyliminium cations, which were generated by low-temperature electrolysis of carbamates, were reduced electrochemically in the absence of radical acceptors. The homo coupling products formed effectively, suggesting that the one-electron reduction of the acyliminium cation produced the corresponding carbon-centered radical. Next, the electrochemical reduction of the acyliminium cations in the presence of electron deficient olefins was examined. The cross coupling products were obtained in good to-moderate yields. A mechanism involving radical addition to the double bond followed by the reduction of the resulting radical to the carbanion was suggested. The overall transformation serves as redox-mediated formal addition of C-H to C=C. The present strategy opens new opportunities to manipulate reactive carbon species using redox processes in organic synthesis. PMID- 11772059 TI - Factors involved in the formation of amorphous and crystalline calcium carbonate: a study of an ascidian skeleton. AB - The majority of invertebrate skeletal tissues are composed of the most stable crystalline polymorphs of CaCO(3), calcite, and/or aragonite. Here we describe a composite skeletal tissue from an ascidian in which amorphous and crystalline calcium carbonate coexist in well-defined domains separated by an organic sheath. Each biogenic mineral phase has a characteristic Mg content (5.9 and 1.7 mol %, respectively) and concentration of intramineral proteins (0.05 and 0.01 wt %, respectively). Macromolecular extracts from various biogenic amorphous calcium carbonate (ACC) skeletons are typically glycoproteins, rich in glutamic acid and hydroxyamino acids. The proteins from the crystalline calcitic phases are aspartate-rich. Macromolecules extracted from biogenic ACC induced the formation of stabilized ACC and/or inhibited crystallization of calcite in vitro. The yield of the synthetic ACC was 15-20%. The presence of Mg facilitated the stabilization of ACC: the protein content in synthetic ACC was 0.12 wt % in the absence of Mg and 0.07 wt % in the presence of Mg (the Mg content in the precipitate was 8.5 mol %). In contrast, the macromolecules extracted from the calcitic layer induced the formation of calcite crystals with modified morphology similar to that expressed by the original biogenic calcite. We suggest that specialized macromolecules and magnesium ions may cooperate in the stabilization of intrinsically unstable amorphous calcium carbonate and in the formation of complex ACC/calcite tissues in vivo. PMID- 11772060 TI - The rate of homolysis of adducts of peroxynitrite to the C=O double bond. AB - Nucleophilic addition of the peroxynitrite anion, ONOO(-), to the two prototypical carbonyl compounds, acetaldehyde and acetone, was investigated in the pH interval 7.4-14. The process is initiated by fast equilibration between the reactants and the corresponding tetrahedral adduct anion, the equilibrium being strongly shifted to the reactant side. The adduct anion also undergoes fast protonation by water and added buffers. Consequently, the rate of the bimolecular reaction between ONOO(-) and the carbonyl is strongly dependent on the pH and on the concentration of the buffer. The pK(a) of the carbonyl-ONOO adduct was estimated to be approximately 11.8 and approximately 12.3 for acetone and acetaldehyde, respectively. It is shown that both the anionic and the neutral adducts suffer fast homolysis along the weak O-O bond to yield free alkoxyl and nitrogen dioxide radicals. The yield of free radicals was determined to be about 15% with both carbonyl compounds at low and high pH, while the remainder collapses to molecular products in the solvent cage. The rate constants for the homolysis of the adducts vary from ca. 3 x 10(5) to ca. 5 x 10(6) s(-1), suggesting that they cannot act as oxidants in biological systems. This small variation around a mean value of about 10(6) s(-1) suggests that the O-O bond in the adduct is rather insensitive to its protonation state and to the nature of its carbonyl precursor. An overall reaction scheme was proposed, and all the corresponding rate constants were evaluated. Finally, thermokinetic considerations were employed to argue that the formation of dioxirane as an intermediate in the reaction of ONOO(-) with acetone is an unlikely process. PMID- 11772061 TI - Structure and chemistry of 1-silafluorenyl dianion, its derivatives, and an organosilicon diradical dianion. AB - 1-Silafluorene dianion was synthesized by potassium reduction of 1,1-dichloro-1 silafluorene in refluxing THF. The X-ray structure of 1,1-dipotassio-1 silafluorene (3b) shows C-C bond length equalization in the five-membered silole ring and C-C bond length alternation in the six-membered benzene rings, indicating aromatic delocalization of electrons in the silole ring. The downfield (29)Si chemical shift at 29.0 ppm and theoretical calculations also support electron delocalization in the silole ring of 3b. Dianion salt 3b underwent nucleophilic reactions with Me(3)SiCl and EtBr to form the corresponding disubstituted products. Benzaldehyde underwent reductive coupling in the presence of 3b. Slow oxidation of 3b yielded 1,1'-dipotassio-1,1'-bis(silafluorene) (16). The X-ray structure and (29)Si chemical shift (-38.0 ppm) of 16 indicate localized negative charges at the silicon atoms and no aromatic character. Heating a DME/hexane solution of 3b in the presence of 18-crown-6 led to a novel diradical dianion salt. PMID- 11772062 TI - "@-Tides": the 1,2-dihydro-3(6H)-pyridinone unit as a beta-strand mimic. AB - The cyclic amino acid surrogate 1 was designed to mimic the extended conformation of a peptide unit and to provide hydrogen bond donor and acceptor functions conducive to beta-sheet formation. A convenient synthesis of this unit and solution and solid-phase methods for its incorporation into an oligomer alternating with peptide units have been devised. The resulting "@-tides", as these oligomers have been designated, show a high propensity for self-association in comparison to oligopeptides; insights into the structure and dynamical properties of their antiparallel dimers have been obtained by NMR. PMID- 11772063 TI - Catalytic, enantioselective alkylation of alpha-imino esters: the synthesis of nonnatural alpha-amino acid derivatives. AB - Methodology for the practical synthesis of nonnatural amino acids has been developed through the catalytic, asymmetric alkylation of alpha-imino esters and N,O-acetals by enol silanes, ketene acetals, alkenes, and allylsilanes using chiral transition metal-phosphine complexes as catalysts (1-5 mol %). The alkylation products, which are prepared with high enantioselectivity (up to 99% ee) and diastereoselectivity (up to 25:1/anti:syn), are protected nonnatural amino acids that represent potential precursors to natural products and pharmaceuticals. A kinetic analysis of the catalyzed reaction of alkenes with alpha-imino esters is presented to shed light on the mechanism of this reaction. PMID- 11772064 TI - The elusive vanadate (V(3)O(9))(3-): isolation, crystal structure, and nonaqueous solution behavior. AB - The isolation, crystal structure, and nonaqueous solution characteristics of the first trinuclear vanadate are presented. The crystal structure reveals a six membered cyclic arrangement of alternating vanadium and oxygen atoms for the anion of [(C(4)H(9))(4)N](3)(V(3)O(9)). The (51)V NMR spectrum of this compound in CD(3)CN exhibits multiple peaks. The relative intensities of each resonance can be altered by concentration and temperature changes, the later of which are reversible. Addition of [(C(4)H(9))(4)N]Br and NaClO(4) also perturbs the equilibria between species observed. Conductivity data for [(C(4)H(9))(4)N](3)(V(3)O(9)) in CH(3)CN as a function of concentration display pronounced curvature and indicate formation of a neutral species in solution at the highest concentrations studied. Stoichiometric mixtures of [(C(4)H(9))(4)N](3)(V(3)O(9)) with the known vanadates [(C(4)H(9))(4)N](3)(HV(4)O(12)), [(C(4)H(9))(4)N](3)(V(5)O(14)), and [(C(4)H(9))(4)N](3)(H(3)V(10)O(28)) are prepared and examined by (51)V NMR. Equilibration between the various vanadates is observed and characterized. Resonances for these known vanadates, however, cannot be used to identify the peaks found for [(C(4)H(9))(4)N](3)(V(3)O(9)), alone, in solution. The existence of ion pairs in acetonitrile is the only interpretation for the solution behavior of [(C(4)H(9))(4)N](3)(V(3)O(9)) consistent with all data. As such, we can directly observe each possible ion pairing state by (51)V NMR: (V(3)O(9))(3-) at 555 ppm, [[(C(4)H(9))(4)N](V(3)O(9))] (2-) at -569 ppm, [[(C(4)H(9))(4)N](2)(V(3)O(9))](-) at -576 ppm, and [(C(4)H(9))(4)N](3)(V(3)O(9)) at -628 ppm. To the best of our knowledge, [(C(4)H(9))(4)N](3)(V(3)O(9)) presents the first case in which every possible ion paired state can be observed directly from a parent polyion. Isolation and characterization of this simple metal oxo moiety may now facilitate efforts to design functional polyoxometalates. PMID- 11772066 TI - Role of framework sodium versus local framework structure in determining the hydrothermal stability of MCM-41 mesostructures. AB - Two mesostructured MCM-41 silicas that differ dramatically in hydrothermal stability have been examined by (29)Si MAS NMR spectroscopy and pair distribution function (PDF) analysis of synchrotron X-ray scattering data. The less stable mesostructure assembled from sodium silicate and the substantially more stable derivative made from fumed silica possess equivalent local framework wall structures, as judged by NMR and PDF methods. Approximately 80% of the SiO(4) tetrahedra are fully cross-linked as Q(4) (Si(OSi)(4)) units in both calcined samples. Additionally, the structural correlation distances for the two materials are nearly identical, having values of 1.62(1), approximately 2.60, and 3.09(1) A for the Si-O, O-O, and nearest neighbor Si-Si distances in the framework. Sodium ions in the framework play a crucial role in limiting the hydrothermal stability of the mesostructure. Residual sodium ( approximately 0.05-0.10% Na(2)O) is retained in the MCM-41 made from sodium silicate, even after two ion exchange reactions with ammonium ions in more than 300 - fold excess. The entrapped framework sodium ions catalyze the collapse of the mesopores upon exposure to 20% steam at 800 degrees C for 5 h. The sodium - free mesostructure assembled from fumed silica retains an open framework under the same hydrothermal conditions. The stability of the fumed silica derivative, however, is greatly compromised when doped with as little as 0.10% Na(2)O, thus confirming the deleterious effect of sodium on hydrothermal stability. PMID- 11772065 TI - C-H bond activation by a ferric methoxide complex: modeling the rate-determining step in the mechanism of lipoxygenase. AB - Lipoxygenases are mononuclear non-heme iron enzymes that regio- and stereospecifcally convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active ferric hydroxide species to give a ferrous water species and an organic radical. Reported here are the synthesis and characterization of a ferric model complex, [Fe(III)(PY5)(OMe)](OTf)(2), that reacts with organic substrates in a manner similar to the proposed enzymatic mechanism. The ligand PY5 (2,6-bis(bis(2 pyridyl)methoxymethane)pyridine) was developed to simulate the histidine dominated coordination sphere of mammalian lipoxygenases. The overall monoanionic coordination provided by the endogenous ligands of lipoxygenase confers a strong Lewis acidic character to the active ferric site with an accordingly positive reduction potential. Incorporation of ferrous iron into PY5 and subsequent oxidation yields a stable ferric methoxide species that structurally and chemically resembles the proposed enzymatic ferric hydroxide species. Reactivity with a number of hydrocarbons possessing weak C-H bonds, including a derivative of the enzymatic substrate linoleic acid, scales best with the substrates' bond dissociation energies, rather than pK(a)'s, suggesting a hydrogen atom abstraction mechanism. Thermodynamic analysis of [Fe(III)(PY5)(OMe)](OTf)(2) and the ferrous end-product [Fe(II)(PY5)(MeOH)](OTf)(2) estimates the strength of the O-H bond in the metal bound methanol in the latter to be 83.5 +/- 2.0 kcal mol( 1). The attenuation of this bond relative to free methanol is largely due to the high reduction potential of the ferric site, suggesting that the analogously high reduction potential of the ferric site in LO is what allows the enzyme to perform its unique oxidation chemistry. Comparison of [Fe(III)(PY5)(OMe)](OTf)(2) to other coordination complexes capable of hydrogen atom abstraction shows that, although a strong correlation exists between the thermodynamic driving force of reaction and the rate of reaction, other factors appear to further modulate the reactivity. PMID- 11772067 TI - Origin of attraction and directionality of the pi/pi interaction: model chemistry calculations of benzene dimer interaction. AB - A model chemistry for the evaluation of intermolecular interaction between aromatic molecules (AIMI Model) has been developed. The CCSD(T) interaction energy at the basis set limit has been estimated from the MP2 interaction energy near the basis set limit and the CCSD(T) correction term obtained by using a medium size basis set. The calculated interaction energies of the parallel, T shaped,and slipped-parallel benzene dimers are -1.48, -2.46, and -2.48 kcal/mol, respectively. The substantial attractive interaction in benzene dimer, even where the molecules are well separated, shows that the major source of attraction is not short-range interactions such as charge-transfer but long-range interactions such as electrostatic and dispersion. The inclusion of electron correlation increases attraction significantly. The dispersion interaction is found to be the major source of attraction in the benzene dimer. The orientation dependence of the dimer interaction is mainly controlled by long-range interactions. Although electrostatic interaction is considerably weaker than dispersion interaction, it is highly orientation dependent. Dispersion and electrostatic interactions are both important for the directionality of the benzene dimer interaction. PMID- 11772068 TI - Structure and magnetic properties of nitroxide molecular crystals by density functional calculations employing periodic boundary conditions. AB - The structure and magnetic properties of one-dimensional chains of representative nitroxides have been studied by a density functional model employing periodic boundary conditions. The optimized geometries are in better agreement with experiments than those obtained from optimizations of model dimeric systems. The spin populations and isotropic hyperfine couplings compare well with the values measured by polarized neutron and electron spin resonance experiments. Magnetic couplings computed by the broken symmetry approach reproduce the ferro- or antiferromagnetic behavior of different nitroxides derived from experiments. These results point out the reliability of the computational model and the significant tuning of all the magnetic properties by intermolecular hydrogen bridges. PMID- 11772069 TI - Structure rationalization and topology prediction of two-distinct-component organic crystals: the role of volume fraction and interface topology. AB - We consider here small-length-scale crystal structures with two clearly different molecular components (e.g., hydrophobic and hydrophilic). Using a perspective developed by studies on large-length-scale block copolymers and liquid crystals, we focus on the crystalline interface between the two components. We examine four types of two-component crystals: aromatic ammonium carboxylates, aromatic oligo(ethylene oxides), cyclohexylammonium carboxylates, and ether-thioether compounds. Of the 111 crystal structures found in the Cambridge Structure Database (CSD), 108 adopt one of the five generic topologies found in diblock copolymers: spheres, columns, perforated layers, layers, and bicontinuous structures. As in diblock copolymers, a key factor controlling the interfacial topology is shown to be the volume ratio of the two components. When the volume fraction of one component is less than 30% of the whole, more than five-sixths of the examined crystal structures are of columnar or spherical type. For volume fractions between 40 and 50% more than three-quarters are of lamellar or bicontinuous type. We use this model to predict the topologies of small-length scale two-component crystals. We predict the crystal topolgies of six new crystal structures: three are predicted to be columnar, and the other three, lamellar or bicontinuous. The crystal structures of these systems were then determined by single-crystal X-ray methods. Five of the structures form in topologies consistent with the predictions: three in columns and two in layers. The remaining one forms as a perforated layer instead of the predicted columnar structure. Such predictive accuracy is consistent with the statistics of the CSD investigation. PMID- 11772070 TI - One step Pd(0)-catalyzed synthesis, X-ray analysis, and photophysical properties of cyclopent[hi]aceanthrylene: fullerene-like properties in a nonalternant cyclopentafused aromatic hydrocarbon. AB - A simple procedure for the synthesis of cyclopentafused polycyclic aromatic hydrocarbons (CP-PAH) with Pd(PPh(3))(2)Cl(2) catalyst has been applied to the one-pot palladium(0)-catalyzed coupling of 9,10-dibromoanthracene (1) with 2 methyl-3-butyn-2-ol. Reactions carried out in refluxing benzene in the presence of CuSO(4)/Al(2)O(3) yielded 9,10-dialkynylanthracene 2a, alkynyl aceanthrylene 2b, and 2,7-disubstituted cyclopent[hi]aceanthrylene 2c in 13%, 23%, and 19% purified yields, respectively, with total conversions of 80-90%. Sealed tube reactions without copper at 110 degrees C improved the yield of 2c up to >75%. Single-crystal X-ray analyses of 2a and 2c reveal a three-dimensional hydrogen bonding network, producing a unique crystal packing. The packing structure of 2b is dominated by pi-pi stacking interactions between two aceanthrylene molecules. CP-PAHs 2b and 2c have potentially interesting fullerene-like photophysics. While the UV-vis and fluorescence spectra of 2a (Phi(F) = 0.87) show the characteristic vibronic structure of anthracene, the UV-vis spectra of ruby-red aceanthrylene 2b and greenish-black cyclopent[hi]aceanthrylene 2c extend well into the visible range. Isomers 2b and 2c showed no detectable fluorescence emission. Unlike fullerenes, compounds 2b and 2c are poor singlet oxygen sensitizers with measured (1)O(2) quantum yields of 0.02 and 0.06, respectively. As expected from a simple Huckel analysis, 2c has relatively low two-electron reduction potentials as determined by cyclic voltammetry. PMID- 11772071 TI - Understanding the congener-specific toxicity in polychlorinated dibenzo-p dioxins: chlorination pattern and molecular quadrupole moment. AB - It is well known that the biological activities and toxicities of planar polychlorinated aromatic compounds are extremely sensitive to chlorination pattern. Although their toxic responses have been correlated with the relative affinity for the receptor, the origin of this congener specificity is not well understood. We present a general interpretation of the congener-specific activity in polychlorinated dibenzo-p-dioxins, which concludes that molecular electrostatics is the principal factor determining the structure-activity relationship in this highly controversial environmental pollutant even though this electrostatic interaction represents only a part of the total interaction energy. Through calculations of the molecular charge distribution in the complete set of 76 dioxin congeners, we show that all active congeners share a unique charge distribution pattern, which is quantitatively described in terms of the molecular quadrupole moment (QM). The QM of dioxins changes sensitively and systematically with chlorination pattern. The three-dimensional electrostatic interactions at the receptor-binding site, which are optimized at a specific QM pattern represented by that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, could explain the congener specificity in the binding affinity and toxicity. Although the polarizability also changes systematically with chlorination, it can only account for the effect of the degree of chlorination, not the congener specificity. PMID- 11772072 TI - Structure and photophysics of an old, new molecule: 1,3,6,8 tetraazatricyclo[4.4.1.1(3,8)]dodecane. AB - More than a century after its initial synthesis, the static and dynamic geometry of 1,3,6,8-tetraazatricyclo [4.4.1.1(3,8)]dodecane (TTD), a fully saturated cage like molecule, is finally established. Detection and modeling of the supersonic jet fluorescence excitation and emission spectra show that the molecule undergoes interconversion between two S(4) symmetry minima. The barrier at the D(2d) symmetric conformation is only 105 cm(-1), i.e., approximately 0.3 kcal mol(-1), and is overcome along a carbon-carbon torsional mode of a(2) symmetry. The presence of an S(4) conformation is corroborated by a Raman investigation. When excited to the first excited singlet state, the 3s Rydberg state, the molecule adopts a geometry with D(2d) symmetry. The satisfactory description of the spectroscopy of TTD obtained by a combination of quantum chemical and quantum mechanical models is discussed, and the apparent conflict between the present results and nuclear magnetic resonance and X-ray diffraction experiments is solved. Because of the close analogy between a Rydberg state and the ground state of the radical cation regarding geometry and spectroscopic properties, it is concluded that the radical cation is also of D(2d) symmetry. PMID- 11772073 TI - Electron delocalization in the radical cation of 1,3,6,8 tetraazatricyclo[4.4.1.1(3,8)]dodecane, a 4-nitrogen-7-electron system. AB - The radical cation of 1,3,6,8-tetraazatricyclo [4.4.1.1(3,8)]dodecane (TTD) has been studied using magnetic resonance and optical spectroscopic methods and computational techniques. With the help of deuterated isotopomers, assignments of EPR and resonance Raman spectra could be unequivocally established. The results demonstrate that the radical cation has D(2d) symmetry, and instantaneous electron delocalization over the four equivalent nitrogen atoms occurs. This extensive delocalization in a completely saturated system is a unique feature of the TTD radical cation. The spectroscopy of TTD, in contrast to that of simpler diamines such as 1,4-diaza[2.2.2]bicyclooctane, simultaneously reveals the consequences of orbital interactions through space and through bonds. The relationship between nitrogen pyramidalization and hyperfine coupling constants in nitrogen-centered radical cations with a number of different bonding arrangements is reviewed. PMID- 11772076 TI - Construction of tetrahydrofuran-3-ones from readily available organochalcogen precursors via radical carbonylation/reductive cyclization. AB - [reaction: see text] beta-Hydroxyalkyl aryl chalcogenides, readily available by regioselective ring-opening of epoxides with nucleophilic benzeneselenolate or tellurolate, were O-alkylated by treatment with ethyl propiolate or (E)-1,2 bis(phenylsulfonyl)ethylene. Subsequent carbonylation/reductive cyclization in the presence of AIBN/TTMSS and carbon monoxide (80 atm) afforded tetrahydrofuran 3-ones in moderate to good yields. PMID- 11772077 TI - The lectin-binding properties of six generations of mannose-functionalized dendrimers. AB - [structure: see text] First- through sixth-generation PAMAM dendrimers have been functionalized with mannose residues. Characterization with MALDI-TOF MS and (1)H NMR is reported. Different binding enhancements consistent with monovalent interaction, glycoside clustering, and multivalent binding are observed for different generations of dendrimers. PMID- 11772078 TI - A novel strained undecadiyne cyclophane with interesting dienophilic character. AB - [reaction: see text] Copper-mediated oxidative coupling of 3 afforded the strained product 4 from intramolecular cyclization rather than the triply bridged cyclophane 5 from dimerization. X-ray analysis of the bromo derivative 15 confirmed the distorted nature of the butadiyne bridge (bond angles 164.1 degrees and 153.4 degrees). The distortion in the strained triple bond is reflected in its cycloaddition reactivity. Cyclopentadiene and 1,3-cyclohexandiene afforded the new adduct macrocycles 16 and 17, respectively. PMID- 11772079 TI - A road map to stable, soluble, easily crystallized pentacene derivatives. AB - [structure: see text] A series of 6,13-disubstituted pentacenes, in which the substituents are functionalized ethyne units, were synthesized and analyzed by X ray crystallography. The resulting pentacene derivatives were highly soluble and oxidatively stable and exhibited a significant amount of pi-stacking in the crystal. PMID- 11772080 TI - An approach to the synthesis of the eupomatilones. AB - [structure: see text] A concise approach to the eupomatilone family of lignans is presented. The strategy employs an intramolecularly competitive Ireland-Claisen rearrangement of a densely functionalized bis-allylic ester. The rearrangement serves both to construct the A-ring and to establish the stereochemistry at C(3) and C(4). PMID- 11772081 TI - Malonate crown ethers as building blocks for novel D-pi-A chromophores. AB - [reaction: see text] A series of new crown ethers, incorporating a malonate ester functionality, have been synthesized and derivatized with pi-electron rich aldehydes to give, conjugated, extended "push-pull" compounds. Their ability to bind Lewis acid-like metal cations, such as Mg(2+) and Eu(3+), has been characterized, and the relative stability constants are presented. When the metal cation is bound to the malonate moiety within the crown ether cavity, the D-pi-A character of the molecular structure is greatly enhanced. PMID- 11772082 TI - Palladium on carbon encapsulated in POEPOP(1500): a resin-supported catalyst for hydrogenation reactions. AB - [reaction: see text] A new a versatile catalyst for hydrogenation reactions wherein palladium on carbon is encapsulated in POEPOP(1500)-resin is described. This polymer-supported catalyst has been successfully used in solution phase hydrogenation of a double and a triple bond as well as hydrogenolysis of a benzyl protecting group. While the activity of the new catalyst is marginally lower than standard 10% Pd/C, it has the advantage of being reused several times without significant loss of reactivity. PMID- 11772083 TI - Combinatorial approach to selective multivalent ion pairing in mixed aqueous organic media using bead-supported libraries of unnatural polyamines. AB - [structure: see text] Screening of a bead-supported encoded library of unnatural polyamines against model polyanionic targets (1 and 2) demonstrated that a combinatorial approach can highlight structural selectivity in multivalent ion pairing in aqueous solutions. This approach even provided -NH-2Acc(R)-6Ahx(R)-Et, a highly target-selective triamine sequence that can discriminate between two trisulfonated dyes displaying subtle structural differences. PMID- 11772084 TI - The rearrangement of fluorenylideneallene oxide. A DFT study. AB - [reaction: see text] Density functional calculations indicate that the rearrangement of fluorenyl allene oxide to the spiro fluorenyl cyclopropanone proceeds through the reactive intermediate fluorenyl oxyallyl. The calculated energetics of this conversion are in agreement with that observed experimentally. The spiro fluorenyl cyclopropanone was calculated to have a low activation energy for its conversion to fluorene and carbon monoxide. PMID- 11772085 TI - Chiral relay effect: 4-substituted 1,3-benzoxazol-2-(3H)-ones as achiral templates for enantioselective Diels-Alder reactions. AB - [reaction: see text] A new strategy to control the enantioselectivity of Lewis acid catalyzed reactions has been investigated. The use of N-acryloyl-1,3 benzoxazol-2-(3H)-ones substituted at position 4 leads to the formation of diastereomeric complexes as a result of the presence of a chiral axis. The stereochemical outcome of the reaction is controlled by the chiral catalyst and by the chiral axis, leading to high enantioselectivity improvements and, in one case, to an inversion of enantioselectivity. PMID- 11772086 TI - Studies directed to the total synthesis of ET 743 and analogues thereof: an expeditious route to the ABFGH subunit. AB - [reaction: see text] In model studies directed to the total synthesis of Et743, a strategic S-C bond formation in systems 26 and 27 was demonstrated. It was further shown that Pictet-Spengler cyclization leading to spiro product 33 exhibits very high stereoselection. PMID- 11772087 TI - Rapid and versatile synthesis of functionalized polyhydroxylated fragments. AB - [reaction: see text] The condensation between a functionalized allylstannane and alpha-alkoxyaldehydes allows rapid access to complex and selectively protected trihydroxylated synthons. The stereocontrol of this process is strongly dependent upon the nature and the amount of the Lewis acid employed. PMID- 11772088 TI - Anion-controlled assembly of porphyrin-bicyclic guanidine conjugates. AB - [reaction: see text] Cationic porphyrins 1-3 bearing one, two, and four bicyclic guanidines form highly ordered chiral assemblies in aqueous solutions. The chirality is controlled by the type of the anionic counterpart and results from a spontaneous process. The chiral assemblies of 1-3 relate structurally to the complexes of achiral porphyrins with helical DNA. However, the presence of a chiral template (DNA, poly L-Glu were tested) is not necessary for formation of these specific chiral porphyrin assemblies. PMID- 11772089 TI - First highly stereoselective synthesis of fungicide systhane. AB - [reaction: see text] Highly enantiopure (R)-2-p-chlorophenyl-2-(1H-1,2,4-triazol 1-ylmethyl)hexanenitrile 1 (myclobutanil or systhane) was obtained in six synthetic steps from commercially available 1-hexyne (35% yield, 92% ee). The sulfinyl group controls the two key steps of the synthetic sequence, the highly stereoselective hydrocyanation of vinyl sulfoxides with Et(2)AlCN and the further introduction of the proper functionality into the molecule. PMID- 11772090 TI - Reversible backbone protection enables combinatorial solid-phase ring-closing metathesis reaction (RCM) in peptides. AB - [reaction: see text] Attempts were made to apply the ring-closing metathesis reaction (RCM) to resin-bound peptides with olefinic side chains of different lengths. In a protein-derived homodetic 10mer peptide epitope the RCM reaction did not take place at all. Only by the introduction of the secondary structure disrupting reversible backbone protection Ser(Psi(Me,Me)pro) and subsequent optimized reduction and purification protocols were we able to generate a full set of RCM cyclized peptides. PMID- 11772091 TI - Hybridization properties of aromatic peptide nucleic acids: a novel class of oligonucleotide analogues. AB - [structure: see text] The synthesis of APNA-PNA chimeras containing all four DNA bases will be described. The hybridization properties of APNA-PNA chimeras with DNA and RNA are consistent with plausible intramolecular interactions that could preorganize the oligomers in a duplex or triplex structure with complementary DNA or RNA. PMID- 11772092 TI - Selective ring opening cross metathesis of cyclooctadiene and trisubstituted cycloolefins. AB - [reaction: see text] The selective ring opening cross metathesis of 1,5 cyclooctadiene and trisubstituted cycloolefins with acroyl species is described. The ring-opened products contain electronically differentiated olefins suitable for additional metathesis reactions. Trisubstituted cycloolefins open regioselectively, placing the acroyl cap on the less-substituted terminus. PMID- 11772093 TI - Three-component coupling via the squarate ester cascade as a concise route to the bioactive triquinane sesquiterpene hypnophilin. AB - [reaction: see text] A squarate ester cascade is used to provide in one step, via the coupling of three reactants, a highly oxygenated linear triquinane product. The latter is transformed in nine steps into hypnophilin. The access route involves a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence. PMID- 11772094 TI - Novel functionalized titanium(IV) benzylidenes for the traceless solid-phase synthesis of indoles. AB - [reaction: see text] Titanium(IV) benzylidenes bearing a masked nitrogen nucleophile in the ortho position converted Merrifield resin-bound esters into enol ethers. An unusual nitrogen protecting group, N-silylated tert-butyl carbamate, was employed. One percent TFA released N-Boc indoles in high yield and purity. N-Methyl indoles were also prepared. Cyclative termination was not required to release the chameleon catch. The first example of a carbonyl group within a titanium alkylidene reagent is reported. PMID- 11772095 TI - Construction of substituted cyclohexanones by reductive cyclization of 7-oxo-2,8 alkadienyl esters. AB - [reaction: see text] Cyclization of 7-oxo-2,8-alkadienyl esters upon reaction with triphenylphosphinecopper hydride hexamer stereoselectively yields substituted cyclohexanones having a cis relationship of carbon side chains at C2 and C3. This cyclohexanone construction is particularly useful for preparing 4 alkoxy- or 4-siloxy-2,3-disubstituted cyclohexanones, in which instance stereoselection is > or = 20:1. PMID- 11772096 TI - Enantioselective allylation of beta,gamma-unsaturated aldehydes generated via Lewis acid induced rearrangement of 2-vinyloxiranes. AB - [reaction: see text] 2-Vinyloxiranes have been found to be excellent surrogates to beta,gamma-unsaturated aldehydes. These valuable electrophiles, generated in situ by treatment of a 2-vinyloxirane with a catalytic amount of Sc(OTf)(3), are effectively trapped by the chiral allylating agents based on alpha-pinene, affording bishomoallylic alcohols in high yield and excellent selectivity. PMID- 11772097 TI - Enhanced enantio- and diastereoselectivities via confinement: photorearrangement of 2,4-cyclohexadienones included in zeolites. AB - [reaction: see text] Employing zeolite as the reaction medium, it is possible to change the enantio (from achiral dienones) and diastereo (from chiral dienones) selectivities during the oxa-di-pi-methane rearrangement of 2,4 cyclohexadienones. PMID- 11772098 TI - Resolution of Pd catalyst with tropos biphenylphosphine (BIPHEP) ligand by DM DABN: asymmetric catalysis by an enantiopure BIPHEP-Pd complex. AB - [reaction: see text] The racemic Pd complex with the chirally flexible (tropos) biphenylphosphine (BIPHEP) ligand can be resolved with enantiopure 3,3'-dimethyl 2,2'-diamino-1,1'-binaphthyl (DM-DABN) as a resolving agent at room temperature. The enantiopure BIPHEP-Pd complex is obtained from complexation with enantiopure DABN followed by tropo-inversion into the single BIPHEP-Pd diastereomer at 80 degrees C and protonation at 0 degrees C. The enantiopure BIPHEP-Pd complex can be used as an efficient Lewis acid catalyst for the Diels-Alder reaction at room temperature to give high enantioselectivity (82% ee, 60%). PMID- 11772099 TI - Asymmetric activation of the Pd catalyst bearing the tropos biphenylphosphine (BIPHEP) ligand with the chiral diaminobinaphthyl (DABN) activator. AB - [reaction: see text] The enantio- and diastereomerically pure Pd complex of the tropos biphenylphosphine (BIPHEP) ligand is obtained through complexation of the enantiopure (R)-diaminobinaphthyl (DABN) with either enantiomer of the BIPHEP-Pd catalyst, followed by tropo-inversion of the less favorable (S)-BIPHEP-Pd/(R) DABN diastereomer to the more favorable (R)-BIPHEP-Pd/(R)-DABN diastereomer. The enantiopure BIPHEP-Pd catalyst with DABN affords higher enantioselectivity and catalytic efficiency as an activated Lewis acid catalyst than the enantiopure BIPHEP-Pd catalyst without DABN. PMID- 11772100 TI - Dynamic asymmetric catalysis by diphenylphosphinoferrocene (DPPF)-nickel complexes through control of axial chirality by chiral diamines. AB - [reaction: see text] The enantio- and diastereomerically pure metal complexes of a chirally dynamic diphenylphosphinoferrocene (DPPF) ligand are obtained through coordination of enantiopure diaminobinaphthyl (DABN) to control the axial chirality of DPPF-Pt, -Pd, and -Ni complexes. The DPPF-Ni catalyst with DABN affords higher enantioselectivity and catalytic efficiency than those attained by the Pd or Pt counterparts and [Ni[(R)-dabn]](SbF(6))(2) without DPPF ligand. PMID- 11772101 TI - Novel cyclic sugar imines: carbohydrate mimics and easily elaborated scaffolds for aza-sugars. AB - [reaction: see text] Representative simple or polyhydroxylated, pyrrolidine (e.g, DRAM) or piperidine (e.g., DNJ) imines not only are potential carbohydrate processing enzyme inhibitors that may be formed as regioisomeric variants but also are scaffolds that may be rapidly elaborated to diversely functionalized aza sugars through highly diastereoselective organometallic additions. PMID- 11772102 TI - Suzuki cross-coupling reactions of potassium alkenyltrifluoroborates. AB - [reaction: see text] The palladium-catalyzed coupling reaction of potassium alkenyltrifluoroborates with aryl or alkenyl halides or triflates proceeds readily with good yields. The trifluoroborates are air- and moisture-stable solids that can be stored indefinitely. The cross-coupling can be effected using PdCl(2)(dppf).CH(2)Cl(2) as the catalyst in n-PrOH in the presence of Et(3)N. A variety of functional groups are tolerated. PMID- 11772103 TI - 2,2,2-trifluoroethyl formate: a versatile and selective reagent for the formylation of alcohols, amines, and N-hydroxylamines. AB - [reaction: see text] Treatment of a variety of alcohols, amines, and N hydroxylamines with 2,2,2-trifluoroethyl formate gave the corresponding formylated adducts in high yields. PMID- 11772104 TI - Total synthesis of epi-7-deoxypancratistatin via aza-Payne rearrangement and intramolecular cyclization. AB - [reaction: see text] epi-7-Deoxypancratistatin containing the cis-fused phenanthridone core was synthesized in 12 steps from bromobenzene. Key features of this synthesis include the enzymatic oxidation of bromobenzene with toluene dioxygenase, selective opening of a cyclic sulfate over an aziridine with oxygen nucleophiles, and an intramolecular Lewis acid-catalyzed cyclization onto an epoxy conduramine derived via aza-Payne rearrangement. PMID- 11772106 TI - Regioselective rhodium-catalyzed addition of arylboronic acids to alkynes with a pyridine-substituted water-soluble ligand. AB - [reaction: see text] Alkynyl heteroaromatic compounds reacted with arylboronic acids to give addition products in the presence of [Rh(COD)Cl](2) and pyridine substituted water-soluble ligand. The reactions proceed to give trisubstituted alkenes with high regioselectivity. PMID- 11772105 TI - The preparation of nonracemic secondary alpha-(carbamoyloxy)alkylzinc and copper reagents. A versatile approach to enantioenriched alcohols. AB - [reaction: see text] Chiral alpha-(carbamoyloxy)alkyllithium reagents, prepared using Hoppe's sBuLi/(-)-sparteine methodology, were transmetalated with ZnCl(2). Further transmetalation with CuCN with overall retention of configuration gave chiral species that reacted with various electrophiles to give enantiomerically pure alcohols after deprotection. A short, highly efficient synthesis of an industrially relevant pheromone, japonilure, illustrates the value of the methodology. PMID- 11772107 TI - Concise synthesis and transannular inverse electron demand Diels-Alder reaction of [3](3,6)pyridazino[3](1,3)indolophane. Rapid access to a pentacyclic indoloid system. AB - [reaction: see text] The title compound was synthesized concisely from indole. A 2-fold sequential hydroboration/Suzuki-Miyaura cross-coupling was employed to generate the cyclophane. When heated in N,N-diethylaniline, it underwent a transannular inverse electron demand Diels-Alder (IEDDA) reaction to form a pentacyclic product, which appears to be well suited as a precursor to a variety of indole alkaloids such as strychnine. PMID- 11772108 TI - Indium-mediated intermolecular alkyl radical addition to electron-deficient C [double bond] N bond and C [double bond] C bond in water. AB - [reaction: see text] The intermolecular alkyl radical addition to imine derivatives was studied in aqueous media by using indium as a single-electron transfer radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provided a convenient method for preparing the alpha-amino acids. The indium-mediated radical addition to an electron-deficient C=C bond also proceeded effectively to provide the new carbon-carbon bond-forming method in aqueous media. PMID- 11772109 TI - Conversion of glucuronic acid glycosides to novel bicyclic beta-lactams. AB - [reaction: see text] Methodology for the conversion of glucuronic acid glycosides to novel bicyclic beta-lactams is reported. Using this strategy, we prepared two novel templates suitable for use in combinatorial chemistry strategies for the construction of a number of interesting beta-lactam motifs. Key features of this strategy include a diastereoselective Ferrier reaction of a glucuronic acid glucal, selective beta-lactam ring formation using a cyclic allylic alcohol, and a chemoselective benzylic oxidation. PMID- 11772110 TI - Novel 1,4-benzodiazepines from acylnitroso-derived hetero-Diels-Alder cycloadducts. AB - [reaction: see text] N(4)-Hydroxy-1,4-benzodiazepines were synthesized in a single step from synthetically versatile acylnitroso-derived hetero-Diels-Alder cycloadducts. The efficiency of this transformation was found to be dependent on the NH pK(a) of the cycloadduct sulfonamide. PMID- 11772111 TI - Catalytic, asymmetric Mannich-type reactions of N-acylimino esters for direct formation of N-acylated amino acid derivatives. Efficient synthesis of a novel inhibitor of ceramide trafficking, HPA-12. AB - [reaction: see text] Catalytic, enantioselective Mannich-type reactions of N acylimino esters for direct formation of N-acylated amino acid derivatives are described. A chiral copper catalyst prepared from Cu(OTf)(2) and a chiral diamine ligand is used. A novel inhibitor of ceramide trafficking, HPA-12, is efficiently synthesized using this reaction. PMID- 11772112 TI - Optically pure alpha-(trimethylsilyl)benzyl alcohol: a practical chiral auxiliary for oxocarbenium ion reactions. AB - [reaction: see text] Enantiopure (S)-alpha-(trimethylsilyl)benzyl alcohol (98% ee) was prepared by Noyori's transfer hydrogenation of benzoyltrimethylsilane. The corresponding trimethylsilyl ether was subjected to Marko's silyl modified Sakurai conditions with a variety of aldehydes to afford homoallylic ethers in high diastereoselectivity. The practicality of the alpha-trimethylsilyl benzyl group as an oxocarbenium ion auxiliary was further demonstrated by its efficient deprotection or conversion to a benzyl protecting group. PMID- 11772113 TI - Total synthesis of sphingofungin E from D-glucose. AB - [reaction: see text] Total synthesis of sphingofungin E (1) is described. Overman rearrangement of an allylic trichloroacetimidate derived from diacetone-D-glucose generated tetra-substituted carbon with nitrogen, and subsequent Wittig olefination afforded the highly functionalized part in sphingofungin E (4) stereoselectively. Coupling reaction of 4 with the C(12) hydrophobic part, followed by further manipulation, completed the total synthesis. PMID- 11772115 TI - Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). AB - The beta2-adrenergic receptor agonist salbutamol (albuterol) has been used for many years in the treatment of bronchospasm in patients with asthma. In this patient group, salbutamol is a relatively safe and inexpensive drug, and is easy to administer. Within the last few years, there has been increasing evidence that salbutamol might have immunomodulatory properties both in vitro and in vivo, in different animal models as well as in humans. This has led researchers to consider salbutamol as a potential therapy for several autoimmune diseases, including multiple sclerosis (MS). In this article, we review the literature presenting such evidence, and discuss the possible mechanisms by which salbutamol influences the immune system. We conclude that salbutamol might be an interesting add-on therapy in patients with MS and that further research is warranted. PMID- 11772116 TI - Epidemiology and treatment of hypochondriasis. AB - Although hypochondriasis has been one of the most durable disease concepts in psychopathology, little is known about its epidemiology and treatment. In this article, we review the last three decades of research into these two aspects of hypochondriasis. According to DSM-IV, hypochondriasis is a distressing preoccupation with the fear or thought, based on physical sensations, that one has a serious disease. The prevalence of hypochondriasis in the general population is unknown; however, studies in primary care suggest that the prevalence in this setting is between 0.8 and 4.5%. There are, at present, no conclusive data about specific risk factors for hypochondriasis, although patients with hypochondriasis have higher rates of anxiety, depressive and other somatoform disorders than patients without the disorder. To date, there have been no studies documenting a genetic or familial predisposition for hypochondriasis, or for somatoform disorders in general. Cognitive behavioural therapy has been shown in controlled studies to be efficacious in the treatment of hypochondriasis. Although the evidence is stronger for individual therapy, group cognitive-behavioural therapy may also be useful. Other therapies such as supportive or psychoanalytical psychotherapy may be efficacious for certain patients, but the lack of standardised treatments and controlled studies makes them a less preferable treatment option at present. Little is known about the pharmacological treatment of primary hypochondriasis. The limited number of published studies and the absence of controlled trials make it impossible to be certain of the efficacy of existing medications. On the basis of the available information, however, it appears that the selective serotonin reuptake inhibitors hold promise for the treatment of this disorder. However, more information is needed for their efficacy to be clearly established. PMID- 11772119 TI - Efficacy and safety of tianeptine in major depression: evidence from a 3-month controlled clinical trial versus paroxetine. AB - OBJECTIVE: This study was performed to compare the efficacy and safety of tianeptine and paroxetine in the treatment of major depression. Anxiolytic drug use was systematically reported to provide an indirect evaluation of the anxiolytic activity of both treatments. Zopiclone use was assessed to provide an indirect evaluation of the possible hypnotic activity of both treatments. DESIGN AND SETTING: This was a 3-month controlled, randomised, double-blind clinical trial which involved 82 centres in France. PATIENTS: 277 outpatients who met DSM IV criteria for major depression. INTERVENTIONS: Patients were treated with either tianeptine (12.5mg three times daily) or paroxetine (20mg once daily plus two placebo capsules). The drug dosages could be doubled after 3 weeks if required by the patient's medical state. MAIN OUTCOME MEASURES AND RESULTS: There was a significant decrease in the Montgomery-Asberg Depression Rating Scale score in both groups (from 28.9 at baseline to 11 at endpoint in the tianeptine group, and from 29.6 to 11.6 in the paroxetine group) after 3 months of treatment. No significant difference was evident between the groups. Secondary criteria confirmed the antidepressant efficacy of both medications, with no difference between tianeptine and paroxetine (Hamilton Depression Rating Scale global score at endpoint, Clinical Global Impression final scores, number of responders, delay to-response, rate of dosage doubling at day 21). The anxiolytic and hypnotic consumption rates decreased in both groups, with no significant difference between the groups. There was no significant difference in clinical safety parameters. CONCLUSION: Tianeptine appears to be as effective and as safe as paroxetine for the ambulatory treatment of major depression. PMID- 11772118 TI - The Bech-Rafaelsen Mania Scale in clinical trials of therapies for bipolar disorder: a 20-year review of its use as an outcome measure. AB - Over the last two decades the Bech-Rafaelsen Mania Scale (MAS) has been used extensively in trials that have assessed the efficacy of treatments for bipolar disorder. The extent of its use makes it possible to evaluate the psychometric properties of the scale according to the principles of internal validity, reliability, and external validity. Studies of the internal validity of the MAS have demonstrated that the simple sum of the 11 items of the scale is a sufficient statistic for the assessment of the severity of manic states. Both factor analysis and latent structure analysis (the Rasch analysis) have been used to demonstrate this. The total score of the MAS has been standardised such that scores below 15 indicate hypomania, scores around 20 indicate moderate mania, and scores around 28 indicate severe mania. The inter-observer reliability has been found to be high in a number of studies conducted in various countries. The MAS has shown an acceptable external validity, in terms of both sensitivity and responsiveness. Thus, the MAS was found to be superior to the Clinical Global Impression scale with regard to responsiveness, and sensitivity has been found to be adequate, with the MAS able to demonstrate large drug-placebo differences. Based on pretreatment scores, trials of antimanic therapies can be classified into: (i) ultrashort (1 week) therapy of severe mania; (ii) short-term therapy (3 to 8 weeks) of moderate mania; (iii) short-term therapy of hypomanic or mixed bipolar states; and (iv) long-term (12 months) therapy of bipolar states. The responsiveness of MAS is such that the scale has been able to demonstrated that typical antipsychotics are effective as an ultrashort therapy of severe mania; that lithium and anticonvulsants are effective in the short-term therapy of moderate mania; and that atypical antipsychotics, electroconvulsive therapy (ECT) and transcranial magnetic stimulation seem to have promising effects in the short term therapy of moderate mania. In contrast, the scale has been used to demonstrate that calcium antagonists (e.g. verapamil) are ineffective in the treatment of mania. MAS has also been used to add to the literature on the evidence-based effect of lithium as a short-term therapy for hypomania or mixed bipolar states and as a long-term therapy of bipolar states. PMID- 11772117 TI - Effects of newer antipsychotics on extrapyramidal function. AB - Following acceptance of clozapine as a superior antipsychotic agent with low risk of adverse extrapyramidal syndromes (EPS), such as dystonia, parkinsonism, akathisia or tardive dyskinesia, several novel antipsychotic drugs have been developed with properties modelled on those of clozapine. Though generally considered 'atypical' in their relatively low risk of inducing EPS, these agents vary considerably in their pharmacology and impact on neurological functioning. Although few comparative data are available, the atypical antipsychotics can be tentatively ranked by EPS risk (excluding akathisia and neuroleptic malignant syndrome) in the following order: clozapine < quetiapine < olanzapine = ziprasidone. At higher doses, risperidone is ranked with a higher EPS risk than olanzapine and ziprasidone, but its risk of EPS is lower with lower doses. In general, this ranking is inversely related to antidopaminergic (D2 receptor) potency. The high antiserotonergic (5-HT2A receptor) potency of risperidone, clozapine, ziprasidone and olanzapine, but not quetiapine, as well as the antimuscarinic activity of olanzapine and clozapine may also limit EPS. For the treatment of psychotic reactions to dopamine agonist therapy in Parkinson's disease, clozapine is both effective and relatively well tolerated; quetiapine may be tolerated, olanzapine is not well tolerated, risperidone is poorly tolerated, and amisulpride and ziprasidone have not been well evaluated. Clozapine, perhaps because of its anticholinergic activity, can reduce parkinsonian tremor. It is useful for ongoing psychosis with tardive dyskinesia, especially for dystonic features. No atypical antipsychotic is clearly effective for motor abnormalities in Huntington's disease or Tourette's syndrome, and the effect of these drugs on other neurological disorders have been well evaluated in only small numbers of patients. In summary, with the exception of clozapine, and perhaps quetiapine, atypical antipsychotics have brought only relative avoidance of EPS, strongly encouraging continued searches for novel antipsychotic agents. PMID- 11772120 TI - Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting 1 to 3% of individuals over the age of 65 years. While effective therapy exists for treating the bradykinesia, rigidity and tremor associated with the disease, the cause is unknown. There is no treatment available to prevent or slow the progressive neuronal loss in the substantia nigra and associated decreased levels of dopamine in the striatum that underlie the cardinal features of the disease. Both retrospective and prospective epidemiological studies have consistently demonstrated an inverse association between cigarette smoking and PD, leading to theories that smoking in general and nicotine in particular might be neuroprotective. Nicotine has been shown in animals to stimulate the release of dopamine in the striatum, and to preserve nigral neurons and striatal dopamine levels in laboratory animals with lesioned nigrostriatal pathways. Coffee and caffeine consumption have also been shown in epidemiological studies to be inversely related to PD risk. Caffeine is an adenosine A(2A) receptor antagonist that enhances locomotor activity in animal models of parkinsonism. Theophylline, a related compound that has A(2A) receptor blocking properties, has been shown in one small trial to improve motor function in patients with PD. Recently, potent and highly selective A(2A) receptor antagonists have been developed that have demonstrated improvement in motor function in animal models of parkinsonism. Exciting findings are emerging that demonstrate attenuation of dopaminergic neurotoxicity with caffeine and other adenosine receptor antagonists in mice given the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), suggesting that these compounds may be neuroprotective. Evidence for the neuroprotective potential of nicotine and caffeine is compelling, but further work is needed before testing these and related compounds in clinical trials for both individuals at high risk of developing PD and those with early, untreated disease. PMID- 11772121 TI - Drug treatment of elderly patients with acute myocardial infarction: practical recommendations. AB - Aspirin (acetylsalicylic acid) should be administered to patients on day 1 of an acute myocardial infarction (MI) and continued indefinitely. Early intravenous beta-blockade should be used during acute MI. beta-blockers should be continued indefinitely. Angiotensin-converting enzyme (ACE) inhibitors should be used in patients with acute MI with ST-segment elevation in two or more anterior precordial leads. ACE inhibitors should be used during and after acute MI in patients with chronic heart failure (CHF) or with a left ventricular ejection fraction < or =40%. There are no class I indications for using calcium channel antagonists during and after acute MI. Intravenous heparin should be used in patients with acute MI undergoing coronary revascularisation and in patients at high risk for systemic embolisation. Enoxaparin should be used in patients with non-Q-wave MI. Thrombolytic therapy should be considered in patients with acute MI with ST-segment elevation in contiguous leads of a 12-lead electrocardiogram or with left bundle branch block. Platelet glycoprotein IIb/IIIa inhibitors should be administered intravenously as an adjunct to heparin and aspirin in patients with non-Q-wave MI. Intravenous nitroglycerin should be used: (i) for the first 24 to 48 hours in patients with acute MI and CHF, large anterior MI, persistent ischaemia or hypertension; and (ii) continued beyond 48 hours in patients with recurrent angina pectoris or persistent pulmonary congestion. Long acting nitrates should be given after MI, along with beta-blockers, to patients with angina pectoris. There are no class I indications for using intravenous magnesium during acute MI. The routine use of antiarrhythmic drugs other than beta-blockers during and after acute MI is not recommended. PMID- 11772122 TI - Optimal management of patients with non-ulcer dyspepsia: considerations for the treatment of the elderly. AB - Optimal therapy for patients with non-ulcer dyspepsia still remains elusive. Increasing consensus on the definition of non-ulcer dyspepsia may improve the design of clinical trials and result in more effective therapies for this common condition. This paper reviews the investigation, pathophysiology and therapy of non-ulcer dyspepsia in order to formulate management strategies in the elderly. The best outcome for the patient can be achieved by detailed evaluation, leading to therapy targeted to obvious precipitating factors such as dyspepsia-inducing medications and other aggravating factors such as slow-transit constipation. Prokinetics and, to a lesser extent, H(2) receptor antagonists are the main medications of choice. Cisapride, the best studied prokinetic, has been withdrawn from the market in certain countries because some patients experienced dangerous cardiac arrhythmias, especially when cisapride was given with potent inhibitors of cytochrome P450 3A4. Time spent on reassurance and judicious use of antidepressants for the right patient can help improve symptoms. In the elderly, however, persistent symptoms should be re-evaluated because of the increased incidence of malignancy. PMID- 11772123 TI - Diagnosis and treatment of allergic skin disorders in the elderly. AB - Allergic skin disorders in the elderly may arise from contact with or ingestion of offending allergens. Itching associated with skin allergy must be distinguished from other causes of itching in the elderly such as xerosis, itching due to systemic disease and bullous disease. Although elderly people have somewhat decreased cell-mediated immunity and may be harder to sensitise under experimental conditions, they have had many years to acquire allergic responses, and therefore develop contact dermatitis frequently. Patch testing is a valuable tool to diagnose contact allergy and should be used often in the elderly, particularly in patients at high risk of contact dermatitis, such as those with chronic lower extremity dermatitis or ulcers due to venous stasis. When prescribing topical medications to high risk patients, a knowledge of the common sensitisers is important. In addition to allergy to medicaments and dressings used to treat stasis ulcers, contact allergy to dental prostheses and medications used to treat ocular disease are common in the elderly as a result of increased usage and exposure. Rash caused by ingested allergens is much more commonly due to medications than to food in the elderly. Allergic noneczematous dermatoses in the elderly are commonly drug-induced. Urticarial skin reactions are often associated with the administration of antibacterials, nonsteroidal anti inflammatory drugs (NSAIDs), antidepressants or opioids. Morbilliform rashes are a common sign of systemic reaction to anticonvulsants, gold, allopurinol or diuretics. Phototoxic reactions may be associated with the administration of tetracyclines, diuretics, NSAIDs and antihyperglycaemic agents. Patient-specific variables such as HLA type and concomitant medication may affect the likelihood of an allergic response to medication. Many elderly patients take multiple medications, which can make diagnosis of drug allergy difficult because diagnosis is most commonly accomplished by observing clinical response once the medication is withdrawn. In the case of lichenoid cutaneous reactions, clinical improvement may take several months after withdrawal of the offending drug. Laboratory tests to detect drug-induced allergic skin disorders may be available in the future. PMID- 11772125 TI - Cholinergic adverse effects of cholinesterase inhibitors in Alzheimer's disease: epidemiology and management. AB - Cholinergic adverse effects of acetylcholinesterase inhibitors (AChEIs) are caused by their central and peripheral pharmacological actions on a variety of organ tissues. Gastrointestinal adverse effects predominate and these were relatively common in the phase II and III randomised clinical trials of AChEIs for the treatment of probable Alzheimer's disease. However, in these studies forced and rapid titration of drugs was used, which is not the case in clinical practice. Although there is a risk of pharmacodynamic interactions with other drugs leading to enhanced cholinergic adverse effects, very few of these interactions have proven to be clinically significant. Unresolved issues include the mechanism of syncope and neuromuscular weakness, which should be resolved through structured pharmacovigilance programmes and clinical studies. Loss of bodyweight may prove to be a long term significant complication. As a class, the AChEIs have proven to be well tolerated in the symptomatic treatment of Alzheimer's disease in its mild-to-moderately severe stages. The incidence and clinical significance of cholinergic adverse events will need to be carefully studied if the drugs are used for indications other than Alzheimer's disease. PMID- 11772124 TI - Liver function and phase I drug metabolism in the elderly: a paradox. AB - Aging is accompanied by marked changes in the physiology of many organs, as well as in their constituent cells. These nonpathological alterations in structure and/or function may affect normal physiological processes in the elderly (individuals > 65 years), for example drug disposition. The liver plays a major role in drug clearance and aging has been reported to diminish this hepatic capacity, particularly the clearance of drugs that undergo mandatory oxidation by the microsomal cytochrome P450-dependent mono-oxygenase systems. Liver volume and blood flow decline with age in humans and, no doubt, this contributes to the diminished clearance of drugs that exhibit first-pass kinetic profiles. Changes in liver morphology with aging that have been described in rodents are limited to the hepatocytes, for example accumulation of dense bodies and loss of smooth surfaced endoplasmic reticulum. There is no evidence that the increase in intracellular lipofuscin adversely affects hepatocyte functions. A number of studies have documented significant age-related declines in the amounts, specific activities and rates of induction of liver microsomal mono-oxygenases in inbred male rats. On the basis of a variety of clinical tests, most liver functions in humans appear to be well preserved. The most remarkable characteristic of liver function in the elderly is the increase in interindividual variability, a feature that may obscure age-related differences. Most in vitro studies using nonhuman primate or human liver tissue did not detect age-related deficiencies in cytochrome P450-dependent microsomal mono-oxygenases. On the other hand, there have been recent reports of age-related, but not gender-related, declines in the in vitro activities of several human liver mono-oxygenases, for example the cytochrome P450 isoform CYP3A. Nevertheless, reduced liver volume and blood flow in the elderly permit the reconciliation of: the in vivo clinical pharmacokinetic data indicative of reduced hepatic drug clearance; and the absence of significant age-related declines in the amounts or in vitro activities of liver microsomal mono-oxygenases. PMID- 11772126 TI - Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women. AB - The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronised, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronised, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomised, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomised, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL) cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhoea, oedema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favourable uterine bleeding profile that improved over time. In a randomised trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomised studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favourable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women. PMID- 11772127 TI - Renal toxicity with sevoflurane: a storm in a teacup? AB - The inhaled anaesthetic sevoflurane is metabolised into two products that have the potential to produce renal injury. Fluoride ions are produced by oxidative defluorination of sevoflurane by the cytochrome P450 system in the liver. Until recently, inorganic fluoride has been thought to be the aetiological agent responsible for fluorinated anaesthetic nephrotoxicity, with a toxic concentration threshold of 50 micromol/L in serum. However, studies of sevoflurane administration in animals and humans have not shown evidence of fluoride-induced nephrotoxicity, despite serum fluoride concentrations in this range. Compound A (fluoromethyl-2,2-difluoro-1-[trifluoromethyl] vinyl ether) is a breakdown product of sevoflurane produced by its interaction with carbon dioxide absorbents in the anaesthesia machine. The patient then inhales compound A. Compound A produces evidence of transient renal injury in rats. The mechanism of compound A renal toxicity is controversial, with the debate focused on the role of the renal cysteine conjugate beta-lyase pathway in the biotransformation of compound A. The significance of this debate centres on the fact that the beta lyase pathway is 10- to 30-fold less active in humans than in rats. Therefore, if biotransformation by this pathway is responsible for the production of nephrotoxic metabolites of compound A, humans may be less susceptible to compound A renal toxicity than are rats. In three studies in human volunteers and one in surgical patients, prolonged (8-hour) sevoflurane exposures and low fresh gas flow rates resulted in significant exposures to compound A. Transient abnormalities were found in biochemical markers of renal injury measured in urine. These studies suggested that sevoflurane can result in renal toxicity, mediated by compound A, under specific circumstances. However, other studies using prolonged sevoflurane administration at low flow rates did not find evidence of renal injury. Finally, there are substantial data to document the safety of sevoflurane administered for shorter durations or at higher fresh gas flow rates. Therefore, the United States Food and Drug Administration recommends the use of sevoflurane with fresh gas flow rates at least 1 L/min for exposures up to 1 hour and at least 2 L/min for exposures greater than 1 hour. We believe this is a rational, cautious approach based on available data. However, it is important to note that other countries have not recommended such limitations on the clinical use of sevoflurane and problems have not been noted. PMID- 11772128 TI - Interactions between herbal medicines and prescribed drugs: a systematic review. AB - Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions. PMID- 11772129 TI - Treatment options in hormone-refractory prostate cancer: current and future approaches. AB - Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone refractory prostate cancer (HRPC) have a median survival of approximately 18 months and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone. Until recently, cytotoxic chemotherapy was felt to be relatively ineffective in the treatment of HRPC. Combination regimens incorporating new active agents have demonstrated significant activity in this setting, renewing interest in the use of chemotherapy to treat HRPC. Recent advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumour cell. Biologic agents now in development include those capable of altering signal transduction, blocking angiogenesis, inhibiting cell cycle progression, and stimulating apoptosis. In addition, many types of immune therapies are showing promise. Evaluating these agents, and incorporating them into existing regimens, are major goals of ongoing clinical research in advanced prostate cancer. PMID- 11772130 TI - Postanaesthetic shivering: epidemiology, pathophysiology, and approaches to prevention and management. AB - Along with nausea and vomiting, postanaesthetic shivering is one of the leading causes of discomfort for patients recovering from general anaesthesia. The distinguishing factor during electromyogram recordings between patients with postanaesthetic shivering and shivering in fully awake patients is the existence of clonus similar to that recorded in patients with spinal cord transection. Clonus coexists with the classic waxing and waning signals associated with cutaneous vasoconstriction (thermoregulatory shivering). The primary cause of postanaesthetic shivering is peroperative hypothermia, which sets in because of anaesthetic-induced inhibition of thermoregulation. However, shivering associated with cutaneous vasodilatation (non-thermoregulatory shivering) also occurs, one of the origins of which is postoperative pain. Apart from causing discomfort and aggravation of pain, postanaesthetic shivering increases metabolic demand proportionally to the solicited muscle mass and the cardiac capacity of the patient. No link has been demonstrated between the occurrence of shivering and an increase in cardiac morbidity, but it is preferable to avoid postanaesthetic shivering because it is oxygen draining. Prevention mainly entails preventing peroperative hypothermia by actively rewarming the patient. Postoperative skin surface rewarming is a rapid way of obtaining the threshold shivering temperature while raising the skin temperature and improving the comfort of the patient. However, it is less efficient than certain drugs such as meperidine, clonidine or tramadol, which act by reducing the shivering threshold temperature. PMID- 11772132 TI - Once-weekly fluoxetine. AB - The relatively long half-life of the selective serotonin reuptake inhibitor fluoxetine has allowed the development of a delayed-release (enteric-coated) formulation containing 90 mg fluoxetine per capsule for once-weekly oral administration. The cumulative relapse rate in patients switched to once-weekly fluoxetine 90 mg for 25 weeks (after responding to 13 weeks of fluoxetine 20 mg/day) was similar to that in patients continuing to receive fluoxetine 20 mg/day and significantly lower than seen in patients switched to placebo. The efficacy of the once-weekly formulation was also similar to that of the daily formulation in other assessment parameters (modified 17-item Hamilton Rating Scale for Depression, Clinical Global Impressions - Severity of Illness Scale). Patient compliance (measured using an electronically monitored tablet bottle) was maintained at 87.5% in evaluable patients receiving once-weekly fluoxetine 90 mg for 12 weeks from a baseline of 85.4% after responding to 4 weeks of fluoxetine 20 mg/day; in contrast, compliance declined significantly (from 87.3% at baseline to 79.4%; p < 0.001) in patients continuing to receive 20 mg/day for 12 weeks. Once-weekly fluoxetine is well tolerated, with a tolerability profile similar to that of the immediate-release formulation. PMID- 11772135 TI - Cetirizine/pseudoephedrine. AB - Cetirizine is the carboxylated metabolite of hydroxyzine, and has high specific affinity for histamine H(1) receptors. Pseudoephedrine is a sympathomimetic drug that acts directly on alpha-adrenergic receptors. black triangle Cetirizine/pseudoephedrine 5/120 mg twice daily was significantly more effective than intranasal budesonide 100 microg or placebo at improving nasal obstruction, nasal patency and reducing the volume of nasal secretion, and was significantly more effective than intranasal xylometazoline 0.1% with respect to nasal secretion, during house dust mite faeces challenge in three randomised, cross- over studies among volunteers with seasonal or perennial rhinitis. The onset of action of cetirizine/pseudoephedrine was reported to be approximately 30 minutes. black triangle The bioavailability of cetirizine and pseudoephedrine is similar after administration of cetirizine/pseudoephedrine 5/120 mg bilayer tablets or coadministration of cetirizine 5 mg tablets plus pseudoephedrine sustained release (SR) 120 mg caplets. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was significantly more effective than each drug given alone at reducing mean total symptom scores for seasonal or perennial allergic rhinitis in two randomised, double-blind, multicentre trials. In both studies, the mean proportion of days during which the five measured symptoms (nasal obstruction, sneezing, rhinorrhoea, nasal pruritus and ocular pruritus) were absent or mild was significantly greater in recipients of the cetirizine plus pseudoephedrine SR. black triangle In one study, cetirizine 5 mg plus pseudoephedrine SR 120 mg was significantly more effective at reducing nasal obstruction than either drug alone. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was well tolerated in patients with seasonal or perennial allergic rhinitis. The most common adverse events were dry mouth, insomnia, headache, somnolence, asthenia and nervousness. PMID- 11772131 TI - Pharmacological options for the treatment of Tourette's disorder. AB - Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD. However, these are not devoid of adverse effects. Tics only require treatment when they interfere with the functioning of the patient. If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs. The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine. The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed. The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful. ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution. Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam. Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed. PMID- 11772138 TI - Estradiol-intranasal: a review of its use in the management of menopause. AB - Estradiol-intranasal is a nasal spray formulation containing an aqueous solution of 17beta-estradiol that has a unique pulse-like pharmacokinetic profile. In a well designed, placebo-controlled trial estradiol-intranasal 200 to 400 microg/day significantly reduced the incidence and severity of climacteric symptoms in women with moderate to severe menopausal symptoms after 4 and 12 weeks' treatment. The efficacy of estradiol-intranasal 300 microg/day was similar to that of oral estradiol 2 mg/day in this and another double-blind placebo controlled trial. This equivalent efficacy was maintained in a subgroup of women with initially severe symptoms, and in smokers. Reductions in the incidence of atrophic vaginal mucosa and genitourinary symptoms and increases in the karyopyknotic index achieved with estradiol-intranasal 300 microg/day were also similar to those observed with oral estradiol 2 mg/day. Assessments of the effects of estradiol-intranasal on the complications of menopause (increased risk of cardiovascular disease and osteoporosis) are ongoing; however, estradiol intranasal (sequentially combined with a progestogen) produced significant beneficial effects on some lipid parameters and on markers of bone resorption and formation, and bone mineral density in postmenopausal women. Estradiol-intranasal had no significant effects on serum levels of most of the assessed haemostatic factors, or on angiotensinogen or insulin levels. Estradiol-intranasal 100 to 600 microg/day was generally well tolerated in clinical trials and most adverse events were mild to moderate. The most commonly reported events were nasal symptoms and mastalgia. There was no evidence of endometrial hyperplasia with up to 1 year's treatment with estradiol-intranasal 300 microg/day combined with a progestogen. The incidence of mastalgia and withdrawal or breakthrough bleeding was lower with estradiol-intranasal 300 microg/day than with oral estradiol 2 mg/day (both administered with a progestogen) in one trial. In another trial, the incidence of mastalgia was lower with estradiol-intranasal 300 microg/day than with estradiol transdermal 50 microg (both administered with a progestogen). However, the overall incidence of adverse events was similar between the two treatments in this trial. CONCLUSIONS: Estradiol-intranasal 200 to 400 microg/day (optimal initiating dose 300 microg/day) reduces the incidence and severity of menopausal climacteric symptoms and has a good tolerability profile. Thus, evidence to date suggests that estradiol-intranasal is a useful treatment option for menopausal symptoms. PMID- 11772139 TI - Peginterferon-alpha-2a (40 kD): a review of its use in the management of chronic hepatitis C. AB - Peginterferon-alpha-2a (40 kD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a that has been developed to improve on the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. Peginterferon-alpha-2a (40 kD) is produced by the covalent attachment of recombinant interferon-alpha-2a to a branched mobile 40 kD polyethylene glycol moiety, which shields the interferon-alpha-2a molecule from enzymatic degradation, reduces systemic clearance and enables once-weekly administration. Peginterferon-alpha-2a (40 kD) was significantly more effective than interferon-alpha-2a in interferon-alpha therapy-naive adults with chronic hepatitis C in three nonblind, randomised, multicentre trials. Virological responses (intention-to-treat results) were achieved in 44 to 69% of patients with or without cirrhosis after 48 weeks of treatment with peginterferon-alpha-2a (40kD) 180 microg/week; sustained virological responses 24 weeks after the end of treatment occurred in 30 to 39% of patients. Virological responses at the end of treatment and at long-term follow-up were significantly higher than those achieved with interferon-alpha-2a. Peginterferon-alpha-2a (40 kD) was significantly more effective than interferon alpha in patients with or without cirrhosis infected with HCV genotype 1. Sustained biochemical responses achieved with peginterferon-alpha-2a (40 kD) 180 microg/week ranged from 34 to 45% and were significantly higher than with interferon-alpha-2a. Recipients of peginterferon-alpha-2a (40 kD) also experienced histological improvements; 24 weeks after discontinuation of treatment with peginterferon-alpha-2a (40 kD) 180 microg/week, 54 to 63% of patients had a > or =2-point improvement in histological activity index score. Peginterferon-alpha-2a (40 kD) produced histological responses in patients (with or without cirrhosis) with or without a sustained virological response. Peginterferon-alpha-2a (40 kD) produced better results than interferon-alpha-2a alone or interferon-alpha-2b plus oral ribavirin on various measures of quality of life in patients with chronic hepatitis C. The tolerability profile of peginterferon-alpha-2a (40 kD) is broadly similar to that of interferon-alpha-2a in patients with chronic hepatitis C with or without cirrhosis. Headache, fatigue and myalgia are among the most common adverse events. CONCLUSION: Peginterferon alpha-2a (40 kD) administered once weekly produces significantly higher sustained responses, without compromising tolerability, than interferon-alpha-2a administered thrice weekly in noncirrhotic or cirrhotic patients with chronic hepatitis C, including those infected with HCV genotype 1 - a group in whom interferon-alpha treatment has usually been unsuccessful. Peginterferon-alpha-2a (40 kD) is a valuable new treatment option and appears poised to play an important role in the first-line treatment of patients with chronic hepatitis C, including difficult-to-treat patients such as those with compensated cirrhosis and/or those infected with HCV genotype 1. PMID- 11772140 TI - Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. AB - Fentanyl is a synthetic opioid agonist which interacts primarily with the mu opioid receptor. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery by the transdermal therapeutic system. These patches are designed to deliver fentanyl at a constant rate (25, 50, 75 and 100 microg/h), and require replacement every 3 days. Data from randomised, nonblind trials suggest that transdermal fentanyl is as effective as sustained release oral morphine in the treatment of chronic cancer pain, as reported by patients using visual and numerical analogue scales as well as verbal description scales. No obvious differences in health-related quality of life were found in patients with chronic cancer pain when comparing transdermal fentanyl with sustained-release oral morphine. Nevertheless, significantly more patients expressed a preference for transdermal fentanyl than for sustained-release oral morphine after a randomised, nonblind, crossover trial. Because of the formation of a fentanyl depot in the skin tissue, serum fentanyl concentrations increase gradually following initial application, generally levelling off between 12 and 24 hours. Thereafter, they remain relatively constant, with some fluctuation, for the remainder of the 72-hour application period. Once achieved, steady-state plasma fentanyl concentrations can be maintained for as long as the patches are renewed. The most frequently observed adverse events during transdermal fentanyl administration (as with other opioid agonists) included vomiting, nausea and constipation. Data from a nonblind, randomised trials suggest that constipation occurs less frequently in patients receiving transdermal fentanyl than in those given sustained-release oral morphine. The most serious adverse event reported in US premarketing trials was hypoventilation, which occurred with an incidence of approximately 2%. Adverse reactions related to skin and appendages (i.e. rash and application site reactions - erythema, papules, itching and oedema) were reported in 153 patients with cancer at a frequency between 1 and 3%. CONCLUSION: Transdermal fentanyl is a useful opioid-agonist for the treatment of moderate to severe chronic cancer pain. The advantages of transdermal fentanyl include ease of administration and the 3-day application interval. These factors coupled with a lower incidence of constipation are likely to contribute to the reported patient preference of transdermal fentanyl over sustained-release oral morphine. PMID- 11772141 TI - Capecitabine: a review of its use in the treatment of advanced or metastatic colorectal cancer. AB - Capecitabine is an orally administered fluoropyrimidine which is selectively activated in tumour tissue to the active moiety fluorouracil and is cytotoxic through inhibition of DNA synthesis. In patients with advanced or metastatic colorectal cancer, first-line therapy with intermittent capecitabine achieved significantly higher objective tumour response rates than therapy with fluorouracil plus leucovorin in pooled analysis. Response rates were also higher in patients pretreated in the adjuvant setting and whose primary site of metastasis was the lung. However, no significant differences between the two treatment groups were seen in the time to disease progression, time to treatment failure or overall survival. Preliminary data suggest response may be improved by combining capecitabine with other anticancer therapies such as oxaliplatin, irinotecan and radiotherapy. Capecitabine in therapeutic dosage regimens generally has acceptable tolerability. Diarrhoea and hand-and-foot syndrome are the major dose-limiting toxicities associated with capecitabine therapy, with adverse effects generally of a gastrointestinal nature. Overall, diarrhoea, stomatitis, nausea and alopecia were significantly less common with capecitabine than with bolus fluorouracil and leucovorin. In addition, capecitabine recipients experienced significantly less myelosuppression, although more capecitabine recipients discontinued therapy because of adverse events. Importantly, patients spent less time in hospital after capecitabine than after bolus fluorouracil and leucovorin therapy, and the oral route of administration of capecitabine is likely to be preferred. In conclusion, capecitabine has shown superior tumour response and less myelosuppression, although more grade 3 hand-and-foot syndrome, in comparison with the 'Mayo Clinic' regimen of fluorouracil therapy, but is unlikely to improve survival. Significantly, its oral route of administration is likely to be preferred by patients. Future strategies to improve patient response may involve selection of those patients likely to respond best to capecitabine, through determination of relevant enzyme levels and combination of capecitabine with various antineoplastic agents. Data on the effect of the drug on quality of life would help establish its role. In the meantime, capecitabine appears to offer an effective and more convenient alternative to fluorouracil as first-line monotherapy for the treatment of metastatic colorectal cancer. PMID- 11772142 TI - Rabeprazole: an update of its use in acid-related disorders. AB - Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION: Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders. PMID- 11772143 TI - Disclosure of adverse events and errors in healthcare: an ethical perspective. AB - Adverse events and medical errors affecting patient care are recognised internationally as major problems in medicine. The failure of health care professionals and health institutes to address this problem has threatened to undermine public confidence in the health care system as a whole. Less focus has been directed at the ethical issues raised by negative outcomes of care, specifically the issue of disclosure. Efforts to prevent negative outcomes of care must be supplemented by policies of increased honesty and openness with patients and their families about adverse incidents. Disclosure should be made easier, not riskier, for healthcare practitioners so clinicians can learn from mistakes and improve patient care. Ethical guidelines for error disclosure must distinguish between disciplinary action and reporting of adverse incidents. Disclosure of negative outcomes requires tact and good communication skills. Healthcare institutions should provide training for the clinicians in this area, if necessary. As a general rule, patients should be informed of unexpected adverse incidents as soon as possible. Medical staff should be rewarded for adverse event reporting and protected from institutional retaliation on account of errors made in health care. PMID- 11772144 TI - Immunisation safety: a priority of the World Health Organization's Department of Vaccines and Biologicals. AB - In 1999, the World Health Organization (WHO) Department of Vaccines and Biologicals launched the Immunisation Safety Priority Project to boost its activities in this area, with the aim of establishing a comprehensive system to ensure the safety of all immunisations given in national immunisation programmes. Countries are the primary focus of this project. The WHO has a role to play not only because of its technical and normative role but also because of its privileged relationship with country authorities and other partners, its global vision and mandate, and because it is perceived as free from conflicts of interest. There are four areas of focus in the project: quality control and assessment tools to ensure vaccine safety from clinical trials up to and including the point of use;research and development of safer and simpler delivery systems; access to safer and more efficient systems for vaccine delivery and sharps waste management; and mechanisms to respond promptly and effectively to vaccine safety concerns. The project emphasises the importance of advocating safety and developing necessary infrastructure and human resource to properly deal with immunisation related safety issues at a national level. PMID- 11772145 TI - Zanamivir: a review of clinical safety in individuals at high risk of developing influenza-related complications. AB - Post-marketing experience shows zanamivir to be well tolerated in the general population for the treatment and prophylaxis of influenza type A and B infections. Individuals at high-risk of influenza have potentially more to gain from zanamivir therapy. We assessed safety and tolerability findings from treatment and prophylaxis studies in over 982 high-risk subjects. Eight treatment studies involving high-risk subjects have been conducted with zanamivir 10 mg twice daily for 5 days. The incidence and pattern of adverse events was similar in zanamivir and placebo recipients. Lower respiratory adverse events reported by recipients receiving zanamivir occurred at similar or lower frequencies to those receiving placebo. In one treatment study involving 525 patients with asthma or chronic obstructive pulmonary disease, zanamivir recipients had a small but significantly increased mean morning peak expiratory flow rate (PEFR) and evening PEFR compared with placebo during the treatment period (days 1 to 5). Eight prophylaxis studies have been conducted, five in family or community settings and three in nursing homes. Data from these studies demonstrate that zanamivir is well tolerated for prophylaxis. In nursing home studies, where 90% of participants were high risk, the pattern and incidence of adverse events were similar to that reported in otherwise healthy individuals, and similar to both placebo and rimantadine, a comparator in one study. In treatment and prophylaxis studies the incidence and pattern of adverse events in participants > or =65 years or with chronic underlying respiratory disorders was similar for zanamivir or placebo recipients. Overall, zanamivir was well tolerated and study drug discontinuations were low. A small number of deaths have been reported in studies of high-risk elderly individuals, but none were considered to be related to zanamivir. Thus clinical studies have demonstrated that zanamivir has a comparable safety profile in high-risk and otherwise healthy recipients. Approximately 1.72 million treatment courses of zanamivir were prescribed up to the end of January 2001. Many spontaneous adverse event reports received since marketing, a third of these from non-healthcare professionals, reflect the underlying condition being treated. However, a number of events have resulted in changes to the zanamivir prescribing information, including rare reports of bronchospasm, dyspnoea, rash, urticaria and allergic type reactions including facial and oropharyngeal oedema. The reported safety profile of zanamivir, for treatment and prophylaxis of high risk subjects with influenza type A and B infections supports its continued use in these individuals who are likely to benefit most. PMID- 11772146 TI - A benefit-risk assessment of caffeine as an analgesic adjuvant. AB - Caffeine has been an additive in analgesics for many years. However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%. In vitro and in vivo pharmacological research has provided some evidence that caffeine can have anti-nociceptive actions through blockade of adenosine receptors, inhibition of cyclo-oxygenase-2 enzyme synthesis, or by changes in emotion state. Nevertheless, these actions are only considered in some cases. It is suggested that the actual doses of analgesics and caffeine used can influence the analgesic adjuvant effects of caffeine, and doses that are either too low or too high lead to no analgesic enhancement. Clinical trials suggest that caffeine in doses of more than 65 mg may be useful for enhancement of analgesia. However, except for in headache pain, the benefits are equivocal. While adding caffeine to analgesics increases the number of patients who become free from headache [rate ratio = 1.36, 95% confidence interval (CI) 1.17 to 1.58], it also leads to more patients with nervousness and dizziness (relative risk = 1.60, 95% CI 1.26 to 2.03). It is suggested that long-term use or overuse of analgesic medications is associated with rebound headache. However, there is no robust evidence that headache after use or withdrawal of caffeine-containing analgesics is more frequent than after other analgesics. Case-control studies have shown that caffeine-containing analgesics are associated with analgesic nephropathy (odds ratio = 4.9, 95% CI 2.3 to 10.3). However, no specific contribution of caffeine to analgesic nephropathy can be identified from these studies. Whether caffeine produces nephrotoxicity on its own, or increases nephrotoxicity due to analgesics, is yet to be established. PMID- 11772147 TI - Profiles of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolone antibacterials: experience from large cohorts from the Drug Safety Research Unit Prescription-Event Monitoring database. AB - OBJECTIVE: To investigate how frequently serious dysrhythmic cardiovascular, and hepatotoxic events are reported during routine clinical use of fluoroquinolones (quinolones) in general practice. DESIGN: Cohorts prescribed quinolones (cohort sizes: ciprofloxacin 11 477; enoxacin 2790; ofloxacin 11 033 and norfloxacin 11 110; mean age in each cohort of 48.6 to 57.0 years) were selected from the Drug Safety Research Unit's Prescription-Event Monitoring (PEM) database. The monitoring periods were November 1988 to January 1989 for ciprofloxacin; April 1989 to January 1991 for enoxacin; May 1991 to December 1991 for ofloxacin and October 1990 to October 1991 for norfloxacin. Data collected over the total PEM surveillance period on selected gastrointestinal events were extracted and reviewed to identify possible hepatic events, together with selected cardiovascular events associated with dysrhythmias. For each quinolone, times to onset of the event and patient-months of observation (denominator values) were calculated. The analysis was based on two observation periods: rate of event during the first 7 days following dispensing of a prescription for each drug (W(1)), and rate of event during the second to sixth week inclusive (W(2)). RESULTS: Scrutiny of original green forms revealed no evidence of drug-induced hepatic dysfunction within 42 days of drug administration for any of the quinolones monitored. No evidence was found of drug-induced dysrhythmic events associated with enoxacin within 42 days of drug administration. Of the other quinolones, 'atrial fibrillation' was reported most often within 42 days following ciprofloxacin administration, with no change in event rate over that time, crude relative risk (CRR)[W(1)/W(2)] 1.0 [95% confidence interval (CI) 0.02 to 8.92]. Other less serious events associated with dysrhythmia were reported with varying incidence within 42 days of quinolone administration. The crude rate of palpitation did not change significantly over that time for ciprofloxacin, ofloxacin and norfloxacin: CRR 0.83 (95% CI 0.02 to 6.86), 2.00 (95% CI 0.19 to 12.20) and 4.99 (95% CI 0.06 to 391.94), respectively. Syncope and tachycardia were also reported for ofloxacin [CRR 9.99 (95% CI 0.52 to 589.49 for both events)] and ciprofloxacin [1.0 (95% CI 0.02, 8.92)] and 2.50 (95% CI 0.04, 47.96) for syncope and tachycardia, respectively]. CONCLUSION: It cannot be ruled out that some rare hepatic and dysrhythmic events associated with quinolones may be drug related. The primary purpose of PEM is signal generation. Compared with the other quinolones, ciprofloxacin was associated with the highest number of reports of dysrhythmic cardiovascular events occurring within 42 days of administration. This requires further investigation by other types of epidemiological study. PMID- 11772148 TI - Metabolic profile of indapamide sustained-release in patients with hypertension: data from three randomised double-blind studies. AB - OBJECTIVE: To evaluate the influence of indapamide sustained-release (SR) 1.5 mg/day, a thiazide-related sulfonamide diuretic, on serum levels of lipids (total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein cholesterol and triglycerides), glucose and uric acid, and renal function (serum urea and creatinine levels). METHODS: Pooled data from three randomised, double blind, controlled studies are analysed. Two of these studies were of short duration (2 and 3 months), one of which included a 9-month nonblind extension phase, and the third was a 12-month prospective study. Short- and long-term metabolic effects of the treatment could thus be analysed. All studies were conducted in patients with mild-to-moderate hypertension; the total population randomised in these studies comprised 1195 patients, of whom 505 had left ventricular hypertrophy (LVH). RESULTS: After 2 to 3 months' treatment with indapamide SR 1.5 mg/day, there was no significant change from baseline in serum lipid levels and glucose levels. This neutral effect was maintained after 9 and 12 months of treatment. Renal function was not affected by short- or long-term indapamide SR 1.5 mg/day therapy. Serum uric acid level was slightly increased after short-term therapy, but was restored to baseline values during long-term therapy with indapamide SR 1.5 mg/day. CONCLUSIONS: Indapamide SR 1.5 mg/day has no deleterious effect on glucose metabolism, serum levels of lipids and uric acid, or renal function. This antihypertensive agent can be considered to be an attractive therapeutic choice for all patients with mild-to-moderate hypertension, including the elderly and patients with increased cardiovascular risks, i.e. those with LVH. PMID- 11772149 TI - Pharmacogenetic tactics and strategies: implications for paediatrics. AB - Genetic diversity exerts profound effects on variation in human drug response in adults, but comparatively little research that specifically relates to genetically abnormal responses in infancy and childhood has been reported. Specific genetic changes in human enzymes, receptors and other proteins that are implicated in drug response and their associated phenotypic correlates provide needed data for construction of profiles individualised to predict susceptibility to adverse drug reactions. If therapy adheres to such guidelines, failure to respond to drug therapy and drug toxicity among genetically susceptible persons can be greatly minimised or averted. PMID- 11772150 TI - Management of preterm infants with intracardiac thrombi: use of thrombolytic agents. AB - Improvement in neonatal care has led to improvements in survival and patient outcome in preterm infants; however, this improved survival has been associated with the development of secondary complications, such as catheter-associated intravascular and intracardiac thrombus formation with a non-negligible morbidity and mortality. The sick preterm infant is at high risk of catheter-related thrombus formation because of the combination of a high prothrombotic activity, low levels of natural anticoagulants, and various imbalances in the fibrinolytic systems. Based on clinical experience in adults and children, and several neonatal case reports demonstrating the efficacy and tolerability of specific thrombolytic treatment, this approach should be recommended as a first choice treatment in the premature infant with intracardiac or intravascular thrombosis. The thrombolytic agents of choice are urokinase or tissue plasminogen activator (tPA); however, none of them have proven to be superior to the other in terms of efficacy or tolerability, either in adult patients or premature infants. In the past, it has been suggested that newborn infants may require higher doses of thrombolytic agents than adults for effective systemic thrombolysis; however, based on more recent in vitro studies, it seems unlikely that this is true. Nevertheless, systemic (high dose) fibrinolysis is of concern as premature neonates present an increased risk of cerebral haemorrhage during the first weeks of life; therefore, low dose treatment has been proposed with, if possible, direct infusion of the fibrinolytic agent into, or close to, the thrombus. This approach has proven to be efficient and well tolerated in several small case series of newborn and preterm infants. Recommended doses are 1000 to 3000 U/kg/h for urokinase or 0.01 to 0.05 mg/kg/h for tPA. A systemic proteolytic state will not be induced by this low dose; however, specific monitoring of fibrinogen plasma levels has to be recommended. Fibrinogen levels should remain above 100 mg/dL during low dose treatment. Lower levels of fibrinogen will indicate the presence of an unwanted systemic fibrinolytic state. After successful thrombolysis, a follow-up treatment, preferentially with low-molecular-weight heparin for neonates at adjusted doses, should be instituted for at least 6 weeks in the absence of any persisting thrombophilic factor. A longer course (3 to 6 months) of anticoagulation therapy is recommended when thrombophilic factors (i.e. hereditary thrombophilia or central venous catheter still in place) are present. Furthermore, it is recommended that any neonate with thrombosis should be evaluated for hereditary thrombophilia later in life. PMID- 11772152 TI - Choosing therapy for childhood asthma. AB - Inhaled corticosteroids remain the primary long-term treatment for controlling childhood asthma. Sodium cromoglycate (cromolyn sodium) and nedocromil sodium are both well tolerated, but usually less effective, alternatives to corticosteroids. Long-acting beta(2)-agonists (beta(2)-adrenoceptor agonists) may be useful adjuncts in patients already receiving inhaled corticosteroids who require frequent use of short-acting bronchodilators or experience nocturnal exacerbations (i.e. overall asthma control suboptimal). Theophylline has bronchodilator and anti-inflammatory effects and may also be used as an adjunct to inhaled corticosteroids. Leukotriene receptor antagonists are now an alternative as monotherapy in young children with mild persistent asthma, or as adjunctive therapy with inhaled corticosteroids as well. Short-acting inhaled beta(2)-agonists or other short-acting bronchodilators should be used as needed for acute episodes. For inhaled delivery, metered-dose inhalers with spacer devices (holding chambers) may be used as the delivery system in many patients, but the choice of inhalation method must be individualised, based largely on patient acceptance and compliance. Systemic corticosteroids may be used to gain prompt control when initiating long-term therapy in patients with severe, persistent asthma that does not respond to inhaled medication or in patients who are unable to take inhaled medication. The anti-immunoglobulin E antibody, omalizumab, is a novel therapy that attacks a fundamental immunopathological process of asthma and has shown promising results in several clinical trials. PMID- 11772151 TI - Ewing tumour: incidence, prognosis and treatment options. AB - Ewing tumours, i.e. Ewing's sarcoma and malignant peripheral neuroectodermal tumours, are the second most common primary malignant tumours of bone in childhood and adolescence, with an annual incidence rate in Caucasians of 3 per 1 million children <15 years of age. Histopathologically small blue round cell tumours, Ewing tumours show a typical chromosomal rearrangement in >95% of cases linking the EWS gene on chromosome 22q12 to a member of the ETS transcription gene family, most commonly to Fli-1 on 11q24. This fusion contributes to the malignant potential of Ewing tumour cells, indeed antisense oligonucleotides may prevent tumour growth in vitro. After open biopsy, and histological and possibly molecular biological confirmation of the diagnosis, treatment consists of several months of multidrug cytostatic therapy and local therapy. Both surgery and radiotherapy may control local disease, but without consequent cytostatic chemotherapy all patients will eventually succumb to distant metastases. With the use of alkylating agents including doxorubicin, cyclophosphamide and/or ifosfamide, and other cytostatic drugs such as actinomycin D (dactinomycin), vincristine and etoposide, long-term survival can be achieved in >50% of patients with localised disease. Patients with clinically detectable metastases at diagnosis, patients not responding to therapy and patients with disease relapse have a significantly poorer prognosis. Maximum supportive care and local therapy managed by an experienced physician are required in all patients, and inclusion of high-risk patients in phase I and II studies is warranted. Hence, treatment of patients with Ewing tumours should be performed in experienced centres only and preferably within controlled clinical trials. PMID- 11772153 TI - Tolerability profile of atypical antipsychotics in children and adolescents. AB - Antipsychotics are frequently used in the treatment of a variety of neuropsychiatric conditions in children and adolescents. Atypical antipsychotics have come to the forefront in child psychiatry due largely to their tolerability profiles as well as their efficacy. Potential treatment options include clozapine, risperidone, olanzapine, quetiapine and ziprasidone. A number of studies investigating the use of clozapine have been published in children; however, owing to the frequent monitoring required for agranulocytosis, the use of clozapine may be restricted to patients with treatment-refractory disease. With accumulating data on the development of glucose intolerance in adults receiving clozapine, closer monitoring of bodyweight and fasting blood glucose is imperative. Clozapine also has an increased seizure risk, therefore a baseline electroencephalogram should be performed, as well as continued vigilance for this adverse effect. Risperidone is an atypical antipsychotic that is generally well tolerated and numerous studies have been published investigating this drug in children. Unlike clozapine, its receptor interaction profile lends itself toward increased risk of extrapyramidal symptoms (EPS) and hyperprolactinaemia. Bodyweight gain is a common adverse effect, although somewhat less than that reported with olanzapine. Baseline liver function studies prior to initiation of this medication are recommended. Risperidone-induced mania has been reported in adults and, therefore, increased caution should be used when deciding to treat children and adolescents with risperidone, particularly in those with a predisposition toward mania. Olanzapine, like risperidone, has also been associated with onset of mania in adults. Olanzapine has a receptor profile that results in significant risk for bodyweight gain and sedation. Furthermore, this drug has been linked to the development of glucose intolerance; thus, it is important to monitor bodyweight and fasting blood glucose on a frequent basis. Less information is known about quetiapine in children and adolescents. Reports about its efficacy and tolerability vary. Quetiapine appears to have increased risk for sedation and bodyweight gain, albeit less than that of olanzapine. The compound appears to be less likely to induce EPS. Finally, ziprasidone has recently been approved for use in the adult population. This compound, in terms of its receptor profile, has more in common with risperidone. This suggests a potential for increased risk of EPS and hyperprolactinaemia. It also has an increased risk of QTc prolongation; thus, a baseline electrocardiogram is suggested, particularly in those patients with a history of cardiovascular illness. Lack of evidence for bodyweight gain with ziprasidone is a considerable advantage. PMID- 11772154 TI - Accounting for noncompliance in pharmacoeconomic evaluations. AB - Noncompliance with prescribed drug regimens is a widespread phenomenon which results in decreased efficacy and is often associated with increased medical expenditures. Despite this, economic evaluations based on decision-analytic models rarely incorporate noncompliance to allow for the differences in compliance observed between controlled clinical trials and routine clinical practice. This review examines the issues relating to the measurement of noncompliance, and the clinical and economic consequences of noncompliant drug taking behaviour. In order to fully appreciate the clinical (and therefore the economic) consequences of noncompliance, a detailed understanding of the type of noncompliance, the pharmacokinetic and pharmacodynamic properties of the drug and the pathophysiological processes of the diseases being treated is required. These are described in detail, and a classification of drug-disease combinations according to the potential economic impact of the varying forms of noncompliance is set out. Issues are raised to highlight the need for improved modelling of the impact of noncompliance, and to this end, recommendations are made for future analyses. The main points are that compliance should be defined clearly, distinguishing between the various forms of noncompliance, that the assumptions relating to the health status of noncompliers should be explicit and robust, and that sensitivity analysis should be applied appropriately to ascertain the impact of noncompliance on the cost-effectiveness of drug therapies. PMID- 11772155 TI - Incremental cost effectiveness of prophylaxis for cytomegalovirus disease in patients with AIDS. AB - Cytomegalovirus (CMV) disease, an opportunistic complication in patients with AIDS, causes substantial morbidity and has high treatment costs. Although prevention of this disease is highly desirable, incremental cost-effectiveness estimates for proposed prophylactic strategies in the era prior to the availability of highly active antiretroviral therapy (HAART) were unfavourable relative to other specific antimicrobial prophylactic strategies in patients with AIDS. With the availability of HAART, several inputs upon which previous estimates of the incremental cost-effectiveness ratio for anti-CMV prophylaxis were based probably changed substantially. To assess the incremental cost effectiveness of prophylaxis in the HAART era, data are needed on visual outcomes and utility for patients with CMV retinitis and AIDS, on better strategies for identifying subpopulations at high risk for CMV disease and on the prophylactic efficacy of valganciclovir. Cost-effectiveness analysis could potentially contribute by exploring thresholds of population risk, prophylactic effectiveness, and drug pricing in order to identify conditions under which prophylaxis for CMV disease in patients with AIDS could potentially become cost effective. PMID- 11772156 TI - Economic evaluation of collagenase-containing ointment and hydrocolloid dressing in the treatment of pressure ulcers. AB - OBJECTIVE: To evaluate the efficacy and cost effectiveness of two treatments of pressure sores on the heel: a collagenase-containing ointment and a hydrocolloid dressing. DESIGN: Study and cost data were collected prospectively in a randomised clinical trial in The Netherlands by counting the resource use for each patient until wound healing occurred. STUDY PARTICIPANTS: All 24 female study participants were inpatients from the same hospital with grade IV pressure sores on the heel following orthopaedic surgery. INTERVENTIONS: Two different treatment strategies were analysed: a collagenase-containing ointment (Novuxol) and a hydrocolloid dressing (Duoderm). PERSPECTIVE: Hospital perspective. MAIN OUTCOME MEASURES AND RESULTS: The average costs per patient for treatment with the hydrocolloid dressing were about 5% higher than those with the collagenase containing ointment. The treatment costs were similarly distributed within both groups, with 34% for materials and 66% for personnel. The cost-effectiveness analysis revealed that cost savings of 899 Dutch guilders (1998 values) per successfully treated patient could be expected using the collagenase-containing ointment instead of the hydrocolloid dressing. In addition, wound healing was achieved, on average, within a shorter time period with the collagenase treatment (10 weeks) compared with the hydrocolloid treatment (14 weeks). The robustness of the results were also tested using sensitivity analyses. These analyses served to confirm that collagenase treatment provides a better cost-effectiveness ratio than hydrocolloid treatment. CONCLUSIONS: With regard to overall costs and costs per successfully treated patient, this study showed collagenase treatment to be more cost effective than the hydrocolloid treatment in patients with grade IV pressure sores on the heel and that the amount of time needed for wound healing was shorter. PMID- 11772157 TI - Direct costs of schizophrenia in Italian community psychiatric services. AB - OBJECTIVE: To estimate resource utilisation and direct costs of treatment for patients with schizophrenia in Italian Community Mental Health Centers (CMHCs). DESIGN: Multicentre, retrospective observational study. CMHCs recruited all patients who attended a follow-up consultation during the period September to December 1998. At enrollment, psychiatrists completed a questionnaire on consumption of resources in the 2 months before recruitment. SETTING: 14 CMHCs. PERSPECTIVE: Italian National Health Service (INHS). PATIENTS: 702 patients with a diagnosis of schizophrenia or other psychotic disorders, defined according to the Diagnostic and Statistical Manual of Mental Disorders-fourth edition. These patients had been followed by the CMHCs for at least 2 years and attended a follow-up consultation either during the period September to December 1998 or on randomly selected days during this period. Patients were classified into seven groups according to their diagnosis. RESULTS: The mean direct cost of patients with schizophrenia in the 2-month observation period was 2,234,475 Italian lire [L] (1154.01 Euro; EUR); direct costs ranged from L.1,545,818 to L.2,775,658 (EUR798.35 to EUR1433.51) by prognostic group. There was wide variability for prognostic groups in the impact of most cost components on total cost. Admissions accounted for between 11.4 and 56.3% of the total cost, daycare centre days for between 11.3 and 35.5%, home visits for 7.8 to 16.4%, and day-hospital days for 5.4 to 32.8%. Antipsychotics and anxiolytics were the most prescribed drugs and also the most costly. CONCLUSION: Despite the limitations of the study related to the short period considered, we believe this study offers some interesting information on the burden of schizophrenia, a disease for which its cost has received limited attention so far in Italy. PMID- 11772158 TI - Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer. AB - Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second line treatment. CONCLUSIONS: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin- a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer. PMID- 11772159 TI - Endogenous anabolic hormone responses to endurance versus resistance exercise and training in women. AB - Research in exercise endocrinology has flourished over the past few decades. In general, research examining short- and long-term hormone responses to endurance exercise preceded studies on resistance exercise, and research on women lagged behind research on men. Sufficient data are now available to allow a comparison of endogenous anabolic hormone responses to endurance versus resistance exercise and training in women. Circulating levels of testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate, estradiol, growth hormone and cortisol have been shown to increase in response to an acute bout of endurance exercise in women. However, only growth hormone, estradiol and cortisol have been reported to increase following resistance exercise. Hormone changes following training, either endurance or resistance, have been variable, probably because of differences in experimental design and major differences in the length, intensity and volume of training programmes. With the notable exception of growth hormone, the anabolic hormones reviewed here appear to decline with endurance training. Resistance training has little effect on resting hormone levels, except insulin-like growth factor-I, which has been shown to increase following a training programme. These hormone changes potentially have both metabolic and hypertrophic implications, and future research needs to focus on the biological significance of these adaptations. PMID- 11772160 TI - Physiology of wheelchair racing in athletes with spinal cord injury. AB - Wheelchair racing is one of the most popular sporting activities of individuals with spinal cord injury. Athletes with this impairment have unique changes in metabolic, cardiorespiratory, neuromuscular and thermoregulatory systems, which reduce their overall physiological capacity compared with able-bodied individuals or individuals with other types of impairments. This review on spinal cord injury: presents the International Stoke Mandeville Games Federation classification of wheelchair athletes; describes methods commonly used to characterise anaerobic and aerobic fitness; presents the findings of physiological studies that have evaluated wheelchair racing performance; identifies the risks associated with temperature regulation when competing in wheelchair races; and discusses special conditions that can influence wheelchair racing performance. Currently there is limited research that has examined the relationship between sprint or distance wheelchair racing performance and the anaerobic and aerobic components of physical fitness. Although the descriptive evidence indicates that the profiles of these athletes reflect their training and participation in these specific events, the association between their physiological profiles and real or simulated racing performance is unclear. The generally accepted concept that high values of aerobic and anaerobic power are strongly correlated with endurance and sprint racing performance, respectively, are not necessarily true in this population. Athletes with spinal cord injury have an impaired thermoregulatory capacity, because the compromised autonomic and somatic nervous system functions disrupt control of skin blood flow and sweating below the level of the lesion. As a result, they may be more susceptible to hyperthermia during distance wheelchair racing performance. Wheelchair athletes should follow recommendations advocated for able-bodied individuals to minimise their risks of heat stress during competition. Many athletes with quadriplegia voluntarily induce autonomic dysreflexia (commonly known as boosting) during distance racing events to improve performance. Experimental evidence indicates that boosting can improve performance time by 10% in elite wheelchair marathon racers during simulated racing, as a result of increased oxygen utilisation in the boosted state. However, since boosting can be dangerous to health, the International Paralympic Committee has banned athletes from voluntarily inducing it during competition. The use of anti-gravity suits to increase lower-body positive pressure can increase the peak oxygen uptake, cardiac output and stroke volume. However, the use of abdominal binders does not influence these physiological responses. An effect of either of these techniques on wheelchair racing performance has not been demonstrated. PMID- 11772162 TI - Aggressive exercise as treatment for chronic low back pain. AB - Exercise has long been a standard of treatment for back pain. Over the last 2 decades, the use of intense, non-pain-contingent exercises for treatment of chronic back pain has received increased advocacy. The main goals of these treatments are to improve functioning of painful lumbar soft tissue and to decrease the fears and concerns of patients about using their backs for daily activities. The methodology of an aggressive quota-based exercise approach to back pain is outlined in this article. This approach relies on objective quantification of physical capabilities, treatment directed at altering these parameters, and repeat quantification for determination of treatment efficacy and positive feedback. By eliminating impairments in back function, altering fears and beliefs about pain, and reducing disability, patients with chronic low back pain can achieve meaningful improvements in their quality of life. PMID- 11772163 TI - Three-dimensional analysis of morphological changes in the maxilla of patients with cleft lip and palate. AB - OBJECTIVE: Three-dimensional (3-D) morphological changes in the maxilla of patients with cleft lip and palate (CLP) have been recorded, mainly using two dimensional cast analyses. Although these seem to be insufficient, no standardized 3-D method has been developed until now. In this study, accuracy, precision, and validity of a newly developed 3-D digital computer-aided procedure to visualize and metrically analyze the growth of the edentulous maxilla of infants with CLP have been evaluated. PATIENTS: The method was applied to 10 infants with complete unilateral CLP. INTERVENTIONS: Consecutive casts of the maxilla (1 week and 3, 6, and 12 months) of each patient were optically measured with a 3-D laser scanner. Following digitizing, the casts were computer reconstructed, aligned, and superimposed using specialized computer software. The distances between the surfaces were measured. Additionally, the surfaces were segmented perpendicular to the alveolar crest, the reference points being C1, C1', C2, C2', and I. The volumes of the resulting segments were determined and compared with one another. RESULTS: The newly developed analysis enables a visualization of the extent and direction of morphological changes in the maxilla of infants with CLP. With this method it is possible to quantify these changes of the volume of defined alveolar segments. CONCLUSIONS: The 3-D analysis developed is an ideal tool for the examination of 3-D morphological changes in the edentulous maxilla of patients with CLP. The results will serve as the starting point for a longitudinal study on the efficacy of different methods, not only of presurgical infant orthopedics but also of surgical procedures. PMID- 11772161 TI - The scientific basis for high-intensity interval training: optimising training programmes and maximising performance in highly trained endurance athletes. AB - While the physiological adaptations that occur following endurance training in previously sedentary and recreationally active individuals are relatively well understood, the adaptations to training in already highly trained endurance athletes remain unclear. While significant improvements in endurance performance and corresponding physiological markers are evident following submaximal endurance training in sedentary and recreationally active groups, an additional increase in submaximal training (i.e. volume) in highly trained individuals does not appear to further enhance either endurance performance or associated physiological variables [e.g. peak oxygen uptake (VO2peak), oxidative enzyme activity]. It seems that, for athletes who are already trained, improvements in endurance performance can be achieved only through high-intensity interval training (HIT). The limited research which has examined changes in muscle enzyme activity in highly trained athletes, following HIT, has revealed no change in oxidative or glycolytic enzyme activity, despite significant improvements in endurance performance (p < 0.05). Instead, an increase in skeletal muscle buffering capacity may be one mechanism responsible for an improvement in endurance performance. Changes in plasma volume, stroke volume, as well as muscle cation pumps, myoglobin, capillary density and fibre type characteristics have yet to be investigated in response to HIT with the highly trained athlete. Information relating to HIT programme optimisation in endurance athletes is also very sparse. Preliminary work using the velocity at which VO2max is achieved (V(max)) as the interval intensity, and fractions (50 to 75%) of the time to exhaustion at V(max) (T(max)) as the interval duration has been successful in eliciting improvements in performance in long-distance runners. However, V(max) and T(max) have not been used with cyclists. Instead, HIT programme optimisation research in cyclists has revealed that repeated supramaximal sprinting may be equally effective as more traditional HIT programmes for eliciting improvements in endurance performance. Further examination of the biochemical and physiological adaptations which accompany different HIT programmes, as well as investigation into the optimal HIT programme for eliciting performance enhancements in highly trained athletes is required. PMID- 11772164 TI - New design of a palatal lift prosthesis combined with a palatal bar. AB - OBJECTIVE: In the past, palatal lift prostheses (PLPs) have been problematic with respect to stability. This stability problem has been addressed by designing a PLP that includes a palatal bar. STRUCTURE: A PLP combined with a palatal bar is functionally characterized by a palatal bar that holds down the posterior palatal plate. By making this location the fulcrum, the force exerted by the soft palate on the lamina actually functions to stabilize the prosthesis instead of acting to overturn it. CASES: This new prosthetic design was applied to patients with cleft palate and those who had undergone cerebral contusion operations. The experimental group was composed of a total of 13 patients (7 men and boys, 6 women and girls) who ranged in age at the time of introduction of the prosthesis from 4 years 6 months old to 54 years 5 months. The period of follow-up after prosthetic insertion ranged from 2 months to 4 years 1 month. In all cases, the stability of the prosthesis was sufficiently maintained. CONCLUSION: Because of increased stability, this technique can be applied to not only adult patients but also children in whom insertion during the deciduous dentition period can be difficult. The new PLP was also found to be effective in patients with cleft palate with a short clinical crown. PMID- 11772165 TI - Alveolar bone grafting in patients with complete clefts: a comparative study between secondary and tertiary bone grafting. AB - OBJECTIVE: This investigation evaluated the results of alveolar bone grafting in patients with complete clefts, comparing secondary alveolar bone grafting (during the mixed stage of dentition) versus tertiary bone grafting (after completion of the second stage of dentition). DESIGN: This was a retrospective study. Of 140 osteoplasties, which all were operated according to the same standardized surgical technique, a clinical and roentgenological follow-up investigation was carried out in a collective of 85 osteoplasties. Clinically we searched for oronasal fistulae, assessed the periodontal status, determined the extent of the gingival attachment in the area of the osteoplasty, and searched for vertical growth disturbances in the area of the osteoplasty. Roentgenologically the height of the alveolar bone in the former clefted area was ascertained. SETTING: Records were obtained from a clinical and radiological study of the Department of Oral and Maxillofacial Surgery of the Medical University of Hannover (Germany). INTERVENTIONS: All patients were operated with the same standardized surgical method. The osteoplastic bridging of the alveolar cleft was performed via a vestibular gingival marginal incision and exclusively by grafting of cancellous bone from the iliac crest. RESULTS: The best results of alveolar bone grafting in cases of secondary osteoplasty were obtained when the lateral incisor or canine had grown into the transplant and had led to a functional stress of the transplanted bone. Approximately good results were to be found in tertiary osteoplasty when the transplanted bone had been stressed functionally through a dental implant. Comparing the secondary with the tertiary osteoplasty, there was a trend of lower resorption in secondary osteoplasty. CONCLUSIONS: Secondary osteoplasty should represent an integral component of any concept for the comprehensive treatment of patients with cleft lip and palate. PMID- 11772166 TI - Nasoalveolar molding and gingivoperiosteoplasty versus alveolar bone graft: an outcome analysis of costs in the treatment of unilateral cleft alveolus. AB - OBJECTIVE: The purpose of this study was to compare the financial impact of two treatment approaches to the unilateral cleft alveolus. The recently advocated nasoalveolar molding (NAM; and gingivoperiosteoplasty (GPP; at the time of lip repair were compared with the traditional approach of secondary alveolar bone graft. DESIGN: The records of all patients (n = 30) with unilateral cleft lip and alveolus treated by a single surgeon during 1985 through 1988 were examined retrospectively. The patients were divided into two groups: group 1 patients (n = 14) were treated by lip repair, primary nasal repair, and secondary alveolar bone graft prior to eruption of permanent dentition; group 2 patients (n = 16) were treated by NAM, GPP, lip repair, and primary nasal repair. Patients who required secondary alveolar bone graft after GPP were noted. The cost of treatment by each protocol was calculated in 1998 dollars. RESULTS: The average cost of treatment for a patient treated by lip repair, primary nasal repair, and secondary alveolar bone graft prior to eruption of permanent dentition was $22,744. Of the 16 patients treated by NAM, GPP, lip repair, and primary nasal repair, 10 required no further treatment of the unilateral cleft alveolus; six patients required secondary alveolar bone graft. The average per-patient treatment cost in this group was $19,745. The average cost savings of NAM and GPP, compared with alveolar bone graft is $2999. CONCLUSIONS: The treatment of unilateral cleft alveolus by nasoalveolar molding and gingivoperiosteoplasty results in substantial cost savings, compared with treatment by secondary alveolar bone graft. PMID- 11772167 TI - Mandibular asymmetry and antigonial notching in individuals with unilateral cleft lip and palate. AB - OBJECTIVE: To determine whether asymmetric antigonial notching is associated with the development of mandibular and lower facial asymmetry in individuals with unilateral cleft lip and palate (UCLP). DESIGN: Retrospective mixed-longitudinal investigation including UCLP and nonaffected orthodontic patients. PARTICIPANTS: All (24) available patients with UCLP treated in our clinic with complete longitudinal records, and 72 skeletal maturation matched noncleft orthodontic patients that served as controls. Subject records included hand-wrist, panoramic, frontal, and 45 degrees oblique cephalometric radiographs. MAIN OUTCOME MEASURES: The development of mandibular asymmetry, measured on oblique cephalometric radiographs, as well as lower facial asymmetry, measured on frontal cephalometric radiographs, was monitored in individuals with UCLP in relation to antigonial notching asymmetry, assessed on panoramic and oblique cephalometric radiographs. RESULTS: First, no statistical differences were found in antigonial notching asymmetry between patients with UCLP and noncleft controls. Second, antigonial notching asymmetry, observed on panoramic and oblique cephalometric radiographs, significantly correlated with the attendant development of mandibular and lower facial asymmetry in individuals with UCLP. Third, the development of mandibular and lower facial asymmetry at pubertal and postpubertal growth spurt stages significantly correlated with antigonial notching asymmetry, measured on panoramic radiographs, at prepubertal and pubertal growth spurt stages, respectively. CONCLUSIONS: The degree of antigonial notching noted on panoramic radiographs can be used as an early indicator of developing mandibular and lower facial asymmetry in individuals with UCLP. PMID- 11772168 TI - Comparison of the effect of supraperiosteal versus subperiosteal dissection on the growing rabbit maxilla. AB - OBJECTIVE: To achieve closure of wide unilateral cleft lip repair without tension of the cleft lip margins, a large undermining, especially of the anterolateral surface of the maxilla, is needed. Two types of dissection are feasible: supraperiosteal or subperiosteal. The aim of this study was to investigate whether there are differences in maxillary growth between healthy rabbits after supraperiosteal or subperiosteal dissection. METHODS: Twenty-four male 7-week-old New Zealand white rabbits were divided randomly into three groups: eight control animals (untreated); eight animals undergoing supraperiosteal dissection of the left surface of the maxilla, and eight animals undergoing subperiosteal dissection of the left surface of the maxilla. All of the treated animals were operated on by the same surgeon at age of 7 weeks and sacrificed at 27 weeks together with control group animals. Seven cephalometric measures (representing aspects of maxillary length, width, and height), on the left side, were taken on the cleaned skull of the rabbits, and the results were analyzed statistically. RESULTS: No significant differences in maxillary growth were noted across the three study groups. CONCLUSIONS: The supraperiosteal or subperiosteal undermining of the anterolateral surface of the maxilla does not seem to interfere with the growth of the normal maxilla in the rabbit. PMID- 11772169 TI - Labial-lingual double articulations in speakers with cleft palate. AB - OBJECTIVE: Labial-lingual double articulations (LLDAs) are speech errors involving simultaneous valving at the lips and in the linguapalatal region. This study investigates the frequency of LLDAs occurring for /p/, /b/, and /m/ targets and describes the linguapalatal contact patterns involved in these abnormal articulations. DESIGN: A retrospective study involving analysis of articulatory data from all speakers with cleft palate recorded at a research center over a 10 year period. PARTICIPANTS: Twenty-seven speakers aged 5 to 62 years (median 11 years) with compensatory speech errors associated with repaired cleft palate. MEASURES: The lingual component of LLDAs was identified using electropalatography (EPG). EPG data were recorded simultaneously with acoustic data. Fifteen bilabial targets (/p/, /b/, /m/) per participant were analyzed. LLDAs were identified in cases where complete linguapalatal constriction (as observed from EPG data) occurred throughout the closure phase of bilabial targets. The labial component of LLDAs was identified from clinical observations of the speakers made during productions of bilabial targets. RESULTS: Three speakers (11%) frequently produced LLDAs for bilabial targets. The configuration of tongue-palate contacts involved in the lingual component of the LLDAs differed in each of the three speakers: one speaker had velar constriction, another had alveolar constriction, and the third had simultaneous alveolar-velar constriction. LLDAs did not similarly affect bilabial targets in the three speakers. One speaker produced LLDAs for /p/ and /b/ targets only. Another produced LLDAs for all /m/ targets but inconsistently for /p/ and /b/ targets. The third speaker produced LLDAs for all /b/ targets but inconsistently for /p/ and /m/ targets. CONCLUSION: LLDAs occurred in a minority of speakers investigated. Nevertheless, it is argued that it is important to identify LLDAs for clinical decision making and for research purposes. The results from this study add to current knowledge about abnormal articulations in cleft palate speech, but further research is needed into the precise timing of lip and tongue-palate closures and into the airflow and acoustic characteristics of LLDAs. PMID- 11772170 TI - Assessing intelligibility in speakers with cleft palate: a critical review of the literature. AB - OBJECTIVE: A literature review was conducted in order to investigate three research questions: how is speech intelligibility being measured in speakers with cleft lip and palate? Is intelligibility adequately being distinguished from related measures such as acceptability? Has there been an increased understanding of intelligibility deficits in speakers with cleft lip and palate? Fifty-seven relevant articles published between 1960 and 1998 were included in the analysis. RESULTS: The results showed an increase in the number of articles that included a measure of intelligibility or a similar measure. Several concerns were raised as a result of the review, including the reliability and validity of measures being employed, adequate definition and differentiation of terms, and the need to determine speech and nonspeech variables contributing to reductions in intelligibility. Relevant literature on intelligibility from fields outside cleft lip and palate is reviewed, and a number of recommendations are made regarding the measurement of intelligibility in speakers with cleft lip and palate. PMID- 11772171 TI - Nasalance measures in Marathi consonant-vowel-consonant syllables with pressure consonants produced by children with and without cleft lip and palate. AB - OBJECTIVE: The purpose of this study was to ascertain whether there exist differential nasalance measures for consonant-vowel-consonant syllables consisting of different pressure consonants articulated by Marathi-speaking children with and without repaired cleft lip and palate. PARTICIPANTS: Ten Marathi-speaking children with repaired cleft palate between the ages of 5 and 12 years formed the experimental group. The control group consisted of 10 age- and sex-matched children with no clefts and no history of any hearing, speech, or voice disorder. METHODS AND MATERIALS: The Kay Elemetrics nasometer model 6200-2 (IBM-PC version) was used for obtaining nasalance measurements. Speech material consisted of eight Marathi monosyllabic words consisting of the pressure consonants in the initial position. The correlation between perceptual judgments of nasality and the instrumental measures was studied by computing the Phi coefficient. RESULTS: Results indicate that there exist differential mean nasalance scores for the syllables with different pressure consonants articulated by Marathi-speaking subjects with repaired cleft lip and palate and those without cleft lip and palate. Correlation coefficient computed between the instrumental measures and the perceptual judgments of nasality indicates moderate correlation between the two measures. CONCLUSIONS: Presence of differential nasalance scores may have diagnostic and therapeutic implications. Results also emphasize the need to evaluate nasal resonance in stimuli other than the traditional ones. PMID- 11772172 TI - Facial appearance and attachment in infants with orofacial clefts: a replication. AB - OBJECTIVE: The current study sought to replicate an unexpected finding reported by: relatively unattractive infants at age 3 months were more likely than attractive infants to show secure maternal attachment at age 12 months, a finding unaffected by the diagnosis of cleft lip and palate (CLP), cleft palate only (CPO), or the absence of a cleft condition. DESIGN: We evaluated the effects of diagnosis (CLP, CPO, or no diagnosis) and age (3, 12, and 24 months) on facial attractiveness ratings derived from a modified Q-sort method. SETTING: Craniofacial clinic in an urban children's hospital. PARTICIPANTS: Infants with CLP and CPO and typically developing infants without clefts (n = 126) and their mothers. Ratings were made by 13 adults unfamiliar with cleft conditions. MAIN OUTCOME MEASURES: Facial attractiveness ratings. RESULTS: Infants with CLP were rated as the least attractive at all time points. At ages 12 and 24 months, infants in the CPO group were rated as less attractive than typical infants but more attractive than infants in the CLP group. Typical infants and those with CLP but not CPO-received higher attractiveness ratings with age. As hypothesized, less attractive infants, regardless of diagnosis, were more likely to show secure attachment than were more attractive infants. CONCLUSIONS: We tentatively conclude that the perceived vulnerability of young infants, as indexed by atypical or unattractive facial characteristics, engenders extraordinary protectiveness and responsiveness in some mothers, leading to a higher probability of secure attachment. A test of this hypothesis with a new sample of infants is recommended. PMID- 11772173 TI - Ultrasound diagnosis of craniosynostosis. AB - OBJECTIVE: To retrospectively study prenatal ultrasound images of patients with craniosynostosis to determine the extent to which prenatal diagnosis is possible. METHOD: Prenatal ultrasound images of 19 patients with postnatally diagnosed metopic or coronal suture craniosynostosis were retrospectively reviewed. The 26 ultrasound examinations obtained were compared with normal images and tables of gestation. RESULTS: It was not possible to diagnose craniosynostosis in the first trimester. In the second trimester, Kleeblattschadel was diagnosed at 20.5 weeks. A multilobular shape to the skull and diastasis of the frontotemporal suture was identified. In a second child with Kleeblattschadel, the cephalic index was above normal 86.4 (normal range 70 to 86), and the head circumference to abdominal circumference was increased. In the third trimester, the head shape deformation was more obvious. Brachycephaly diagnosis was made in the second trimester. In Crouzon syndrome the hypertelorism was identified at 19.9 weeks. Plagiocephaly was diagnosed at 21.4 weeks. In trigonocephaly the reduced cephalic index was noted at 18.8 weeks. In the third trimester, the deformity was diagnosed in all cases. CONCLUSION: No diagnosis of craniosynostosis was made in the first trimester. In the second trimester, it was possible to diagnose Kleeblattschadel, trigonocephaly, brachycephaly (bilateral coronal suture craniosynostosis), and plagiocephaly (unilateral coronal suture craniosynostosis) in nine of the examinations. In the third trimester and at term, it was possible to diagnose previously listed conditions from six of the seven examinations obtained. Kleeblattschadel was suspected during original examination. A total of 15 examinations of 26 were correctly diagnosed during this investigation. PMID- 11772174 TI - Validity of the Hfm transgenic mouse as a model for hemifacial microsomia. AB - OBJECTIVE: Our comprehension of hemifacial microsomia (HFM) has been hindered by its diverse phenotype and unclear etiopathogenesis. The conventional view has been that HFM's facial defects result from embryonic hemorrhages in the region of the first and second branchial arches. A more recent model based on a transgenic mutation of a locus termed Hfm (B1 to B3 on chromosome 10) appears to provide an insight into HFM causation. This study investigated the validity of this model by examining the Hfm craniofacial phenotype and histological development of the embryonic head (E13.5 to 17.5). RESULTS: The results confirmed that although the loss-of-function mutation was transmitted in an autosomal dominant manner, the penetrance rate was significantly reduced and only Hfm heterozygotes were viable. The observations here extend the Hfm phenotype beyond microtia and jaw asymmetry to include structural and positional anomalies affecting the external auditory meatus, middle ear, cranial base, maxilla, and pharyngeal structures. Temporomandibular joint (TMJ) development and palatal shelf fusion were also affected in a small number of cases. In addition, some Hfm embryos displayed a novel finding: transposition of the developing inner ear between the tubotympanic recess and cranial base. CONCLUSIONS: These craniofacial features, especially the ear anomalies and facial asymmetry indicate that the Hfm transgenic mouse represents a useful model for the HFM-microtia spectrum. In particular, it supports the hypothesis that at least a proportion of HFM anomalies has a genetic causation mediated via mesenchymal disruptions and possibly embryonic hemorrhages. PMID- 11772175 TI - Guidelines for the design and analysis of studies on nonsyndromic cleft lip and cleft palate in humans: summary report from a Workshop of the International Consortium for Oral Clefts Genetics. AB - OBJECTIVE: The members of the International Consortium for Oral Clefts Genetics recognize the need for collaboration between researchers involved in etiologic studies of nonsyndromic cleft lip and palate and cleft palate. To address this need, the consortium established four working subcommittees: diagnostic and phenotypic assessment, molecular genetic studies, epidemiologic data collection and analysis, and genetic data collection and analysis. These subcommittees were charged with the development of guidelines for data collection and analysis that would facilitate both a priori and a posteriori comparisons and pooling of data from multiple centers. This report presents summary statements of the four subcommittees. PMID- 11772176 TI - Functional analysis of cleft lip and palate patients with modified Rakosi method. AB - OBJECTIVE: The aim of this study was to investigate the mandibular functions of patients with cleft lip and palate (CLP) by means of modified Rakosi Functional Analysis and to test whether there was a risk of tendency to temporomandibular joint disorder when compared with Angle Class I non-CLP patients. DESIGN: Fifteen patients with unilateral CLP with a mean age of 12.2 +/- 1.91 years and randomly selected 15 Angle Class I orthodontic patients with a mean age of 10.5 +/- 2.01 years as a control group. None of the subjects had complaint of symptoms of temporomandibular joint disorder in their histories. All subjects were evaluated using modified Rakosi Functional Analysis method in accordance with a scoring system of the findings. MAIN OUTCOME MEASURES: Intra- and extracapsular clinical functional surveys were taken. A Mann-Whitney U test was used to evaluate the differences between the CLP and non-CLP groups. RESULTS AND CONCLUSION: There was a significant difference (p <.01) between the distributions of the total scores of the two groups. A significant difference (p <.05) in right lateral movement was also observed between the two groups. However, there were no significant but borderline differences in clicking, crepitus, and maximum mouth opening findings between the two groups. Because these results do not explain the reason for the aforementioned differences, further studies seem essential. PMID- 11772177 TI - Cephalometric analysis in submucous cleft palate: comparison of cephalometric data obtained from submucous cleft palate patients with velopharyngeal competence and incompetence. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between craniofacial and nasopharyngeal morphology and velopharyngeal function in submucous cleft palate. DESIGN AND PATIENTS: Fifty-two lateral cephalometric radiographs of 46 submucous cleft palate (SMCP) patients with velopharyngeal competence (24 patients) and incompetence (22 patients) at 4 and 7 years of age were studied. The patients had not received any surgical or orthodontic treatment prior to cephalography being performed. RESULTS: Significant differences were found between cephalometric variables (N-Ba, N-S-Ba angle) in children with velopharyngeal competence and incompetence. However, the results of our study showed that cephalometric data alone are not useful for predicting velopharyngeal function and can not serve as an absolute prognostic indicator. CONCLUSION;There are many factors that can influence velopharyngeal function in SMCP patients. Cephalometric data did not demonstrate a strong relationship to velopharyngeal function. PMID- 11772178 TI - A child with Saethre-Chotzen syndrome, sensorineural hearing loss, and a TWIST mutation. AB - OBJECTIVE: Patients with syndromic craniosynostosis may have associated hearing deficits. A review of hearing loss associated with syndromic craniosynostosis as well as implications of cochlear implantation in the craniosynostosis patients is presented. In the literature, patients with Saethre-Chotzen syndrome have been shown to have conductive or mixed hearing losses. This case report describes a patient with Saethre-Chotzen syndrome caused by a mutation in the TWIST gene who exhibits a severe to profound sensorineural hearing loss. PMID- 11772179 TI - Neonatal permanent jaw constriction because of oral synechiae and Pierre Robin sequence in a child with van der Woude syndrome. AB - OBJECTIVE: To report a newborn with van der Woude syndrome, Pierre Robin sequence, and oral synechiae. Pierre Robin sequence is a rare manifestation of van der Woude syndrome as are oral synechiae. We speculate that the oral synechiae may be causally related to the development of Pierre Robin sequence in this patient. PMID- 11772180 TI - Cleft palate and craniofacial conditions. PMID- 11772181 TI - Urinary tract infections in young febrile infants: is selective testing acceptable? PMID- 11772182 TI - Call for papers on violence. PMID- 11772183 TI - Pediatric palliative care: the time has come. PMID- 11772184 TI - Reviewing manuscripts for Archives of Pediatrics & Adolescent Medicine. PMID- 11772186 TI - Attachment classifications among 18-month-old children of adolescent mothers. AB - OBJECTIVES: To determine (1) patterns of secure vs insecure attachment relationships in infants of adolescent and nonadolescent mothers and (2) if these patterns are mediated by parenting characteristics, including depression, self esteem, parenting stress, child abuse potential, psychological distress, rating of infant temperament, and the caregiving environment. PARTICIPANTS: Fifty-one adolescent mothers and their 18-month-old infants were compared with 76 nonadolescent mothers and their 18-month-old infants. MAIN OUTCOME MEASURES: Infant attachment classifications were assessed via the Ainsworth Strange Situation. Maternal and infant characteristics were obtained through self-report measures. RESULTS: There were no differences in attachment classification between infants of adolescent mothers and nonadolescent mothers. Secure attachment classification was found in 67% of the infants of adolescent mothers and 62% of the infants of nonadolescent mothers. There were significant differences in the self-reported maternal characteristics. Adolescent mothers reported lower self esteem (P<.05), more parenting stress (P<.05), more child abuse potential (P<.05), and provided a lower quality of home environment (P<.05) than nonadolescent mothers. Adolescent mothers also rated their infants as having a higher activity level (P<.05) than infants born to nonadolescent mothers. In multivariate analysis, none of these variables or social classes were found to affect attachment classification. CONCLUSIONS: Infants of adolescent and nonadolescent mothers show similar patterns of attachment. Adolescent and nonadolescent mothers show substantial differences in parenting characteristics and in how they rate their infants' temperaments. However, these differences do not seem to impair the infant-mother attachment relationship. PMID- 11772185 TI - Family perspectives on the quality of pediatric palliative care. AB - BACKGROUND: As a prelude to establishing a Pediatric Palliative Care Program, we solicited information from families about their experiences and their suggestions for improving the quality of end-of-life care. Participants were English- and Spanish-speaking family members of deceased pediatric patients who received care at Lucile Salter Packard Children's Hospital, Stanford University Medical Center, Palo Alto, Calif. METHODS: Sixty-eight family members of 44 deceased children were interviewed regarding treatment, transition to palliative care, and bereavement follow-up. Four clinical social workers and one clinical psychologist reviewed the participants' responses and identified frequently occurring themes. RESULTS: Several areas of unsatisfactory interactions with staff were identified: confusing, inadequate, or uncaring communications regarding treatment or prognosis; preventable oversights in procedures or policies; failure to include or meet the needs of siblings and Spanish-speaking family members; and inconsistent bereavement follow-up. A discrepancy emerged between the high degree of pain described by the families and parents' perceptions that pain had been managed well. Community hospice programs are frequently poorly prepared to serve pediatric patients. CONCLUSIONS: There is a need to improve pediatric palliative care. Recurring themes in the family interviews suggest useful issues to consider in the development of a palliative care program. PMID- 11772187 TI - Ampicillin use in infant fever: a systematic review. AB - OBJECTIVES: To estimate the prevalence of perinatal Listeria monocytogenes and enterococcal infections in outpatient febrile infants and to evaluate the need to treat with ampicillin. DATA SOURCES: Online bibliographies were searched for articles related to serious bacterial infection and fever in infants. Reference lists from selected and review articles were also examined. STUDY SELECTION: Studies that reported rates and types of bacterial infection in febrile outpatients younger than 3 months were included. Those performed outside North America, lacking results by age, or those that evaluated selected patient populations were excluded. DATA EXTRACTION: Two authors independently reviewed the selected articles for inclusion and abstracted the data. DATA SYNTHESIS: Fourteen studies, evaluating 5247 febrile outpatients, were included. The prevalences of L monocytogenes and enterococcal infections were 7.3 (binomial exact 95% confidence interval [CI], 3.5-13.3), 1.9 (95% CI, 0.6-4.4), and 5.6 (95% CI, 0.7-2.1) per 1000 febrile infants in the first, second, and third months of life, respectively. To cover 1 infant with serious bacterial infection caused by L monocytogenes and enterococcal infections, the numbers of febrile infants who would need ampicillin were estimated as 138 (95% CI, 76-288) in the first month, 527 (95% CI, 226-1621) in the second month, and 178 (95% CI, 50-1469) in the third month. Enterococcal infections occurred in all ages studied; there were no Listeria infections after 30 days of age. CONCLUSION: The empirical use of ampicillin to cover febrile infants for L monocytogenes and enterococcal infections is most justifiable in the first month of life. PMID- 11772188 TI - Effects of improved access to safety counseling, products, and home visits on parents' safety practices: results of a randomized trial. AB - OBJECTIVE: To present the results of an intervention trial to enhance parents' home-safety practices through pediatric safety counseling, home visits, and an on site children's safety center where parents receive personalized education and can purchase reduced-cost products. DESIGN: Pediatricians were randomized to a standard- or an enhanced-intervention group. Parents of their patients were enrolled when the patient was 6 months or younger and observed until 12 to 18 months of age. SETTING: A hospital-based pediatric resident continuity clinic that serves families living in low-income, inner-city neighborhoods. PARTICIPANTS: First- and second-year pediatric residents and their patient-parent dyads. INTERVENTIONS: Parents in the standard-intervention group received safety counseling and referral to the children's safety center from their pediatrician. Parents in the enhanced-intervention group received the standard services plus a home-safety visit by a community health worker. OUTCOMES: Home observers assessed the following safety practices: reduction of hot-water temperature, poison storage, and presence of smoke alarms, safety gates for stairs, and ipecac syrup. RESULTS: The prevalence of safety practices ranged from 11% of parents who stored poisons safely to 82% who had a working smoke alarm. No significant differences in safety practices were found between study groups. However, families who visited the children's safety center compared with those who did not had a significantly greater number of safety practices (34% vs 17% had > or 3). CONCLUSIONS: Home visiting was not effective in improving parents' safety practices. Counseling coupled with convenient access to reduced-cost products appears to be an effective strategy for promoting children's home safety. PMID- 11772189 TI - Effect of rapid diagnosis of influenza virus type a on the emergency department management of febrile infants and toddlers. AB - BACKGROUND: Evidence shows that the rapid detection of influenza using an enzyme linked immunosorbent assay decreases antibiotic use in the treatment of pediatric patients. To our knowledge, the effect on other diagnostic testing in an emergency department (ED) has not been examined. OBJECTIVE: To determine the effect of rapid diagnosis of influenza virus type A on the clinical management of febrile infants and toddlers in a pediatric ED at an urban children's hospital. MATERIALS AND METHODS: A retrospective review of ED records from an electronic database was performed. All children 2 to 24 months of age, with a temperature higher than 39 degrees C who had a positive influenza virus type A test result using an enzyme-linked immunosorbent assay from November 1, 1998, through April 30, 2000 (n = 72), were included in this study. Two groups were compared-those who had positive test results reported before discharge from the ED (early diagnosis) and those who had positive test results after discharge (late diagnosis). RESULTS: Forty-seven patients (65%) were in the early diagnosis group and 25 (35%) in the late diagnosis group. The groups were similar for age, temperature, and triage category. Fewer patients in the early diagnosis group received ceftriaxone sodium compared with those in the late diagnosis group (2% vs 24%, P =.006); there were fewer urinalyses (2% vs 24%, P =.006) and complete blood cell counts performed (17% vs 44%, P =.02). CONCLUSIONS: Rapid confirmation of influenza virus type A infection seems to decrease ancillary tests and antibiotic use in febrile infants and toddlers in the ED. A prospective study with a larger group is needed to confirm these findings. PMID- 11772190 TI - Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings' Febrile Infant Study. AB - OBJECTIVE: To determine the predictors and results of urine testing of young febrile infants seen in office settings. DESIGN: Prospective cohort study. SETTING: Offices of 573 pediatric practitioners from 219 practices in the American Academy of Pediatrics Pediatric Research in Office Settings' research network. SUBJECTS: A total of 3066 infants 3 months or younger with temperatures of 38 degrees C or higher were evaluated and treated according to the judgment of their practitioners. MAIN OUTCOME MEASURES: Urine testing results, early and late urinary tract infections (UTIs), and UTIs with bacteremia. RESULTS: Fifty-four percent of the infants initially had urine tested, of whom 10% had a UTI. The height of the fever was associated with urine testing and a UTI among those tested (adjusted odds ratio per degree Celsius, 2.2 for both). Younger age, ill appearance, and lack of a fever source were associated with urine testing but not with a UTI, whereas lack of circumcision (adjusted odds ratio, 11.6), female sex (adjusted odds ratio, 5.4), and longer duration of fever (adjusted odds ratio, 1.8 for fever lasting > or = 24 hours) were not associated with urine testing but were associated with a UTI. Bacteremia accompanied the UTI in 10% of the patients, including 17% of those younger than 1 month. Among 807 infants not initially tested or treated with antibiotics, only 2 had a subsequent documented UTI; both did well. CONCLUSIONS: Practitioners order urine tests selectively, focusing on younger and more ill-appearing infants and on those without an apparent fever source. Such selective urine testing, with close follow-up, was associated with few late UTIs in this large study. Urine testing should focus particularly on uncircumcised boys, girls, the youngest and sickest infants, and those with persistent fever. PMID- 11772191 TI - Role models, ethnic identity, and health-risk behaviors in urban adolescents. AB - BACKGROUND: The assumption that role models or mentors constructively influence adolescent psychological functioning has prompted societal investment in mentoring programs. However, there has been little empirical evaluation of the relationship between role model or mentor characteristics and health behaviors. OBJECTIVES: To describe role model selection in urban adolescents and examine the relationships between role model characteristics, psychosocial functioning, and health-risk behaviors. DESIGN: Cross-sectional survey. PARTICIPANTS: A population based, multiethnic sample of Los Angeles County adolescents aged 12 to 17 years was generated from a 3-stage, area-probability sampling frame. Of 877 adolescents identified, 749 are included in this analysis. METHODS: In-person, in-home interviews were conducted. MAIN OUTCOME MEASURES: Substance use, academic performance, and self-perception (measures of ethnic identify and self-esteem). Ethnic identity was measured by an adaptation of a scale developed by Phinney (J Adolesc Res. 1992;7:156-176) to assess commonalities across ethnic groups. RESULTS: Fifty-six percent of adolescents identified a role model. Higher levels of ethnic identity were associated with moving from identifying no role model to identifying a figure primarily available through the media to identifying a known individual, familial or nonfamilial (P<.001). Having a role model, particularly an individual known to the adolescent, was also associated with higher self esteem (P<.001) and higher grades (P<.05). For white males without custodial fathers, having a role model was associated with decreased substance use (P<.05). CONCLUSION: Role model selection is associated with protective psychosocial characteristics. PMID- 11772192 TI - Parental perceptions of well-child care visits in an inner-city clinic. AB - OBJECTIVES: To assess parental perceptions of the importance of well-child care (WCC) in an inner-city clinic and to determine what type and format of information parents would like to obtain at WCC visits. METHODS: A convenience sample of parents accompanying a child aged 12 years or younger attending an inner-city pediatric teaching clinic completed self-administered written surveys. Parents ranked the importance of WCC overall, as well as its various components, using Likert scales. Parents also responded to checklist-style questions to indicate selected topics they would like to receive more information about and the format of information they preferred (written, talking to the physician, or videotapes in the waiting room). RESULTS: A total of 239 parents completed surveys. Overall they believed WCC was important (91% responded "extremely important" or "very important"). The individual WCC components ranked most important by parents were immunizations, growth and development issues, and the opportunity to discuss behavior or other concerns. The topics of information requested most frequently were how to help their child learn healthy eating habits (55%), how to help their child do well in school (53%), and how to keep their child safe outside of their home (49%). Written information was the format most frequently preferred (65%) by parents for receiving information. CONCLUSIONS: Parents of inner-city children consider WCC important. They want to hear about child health-related issues and prefer a written format. This knowledge can guide health care providers and educators during WCC visits and while teaching. PMID- 11772193 TI - Inpatient childhood asthma treatment: relationship of hospital characteristics to length of stay and cost: analyses of New York State discharge data, 1995. AB - BACKGROUND: There is increasing pressure to optimize asthma treatment efficiency. It is possible that hospital characteristics influence such efficiency. OBJECTIVE: To examine the association of selected hospital characteristics with cost and length of stay (LOS) among pediatric patients with asthma after adjusting for patient characteristics. DESIGN: Secondary analysis of 1995 hospital discharge data in the state of New York. SUBJECTS: Nineteen thousand six hundred eighty-eight patients aged 1 to 17 years with asthma discharged from 206 acute care hospitals in New York in 1995. MAIN OUTCOME MEASURES: Length of stay and hospital cost. ANALYSIS: Hospitals were described with respect to teaching status and ownership. The differences in the distribution of children within each hospital type were assessed by chi(2) tests. In multivariate analyses, hierarchical models were constructed to analyze cost and LOS, adjusting for both hospital- and patient-level covariance. RESULTS: Asthma severity did not meaningfully differ by hospital ownership and teaching status. Public and teaching hospitals had more minority and Medicaid patients. After adjusting for patient- and hospital-level covariates and for the hierarchical nature of the data, there were no statistically significant differences between public and private hospitals in mean cost or LOS. Adjusted mean LOS in teaching hospitals was not significantly shorter, while costs were significantly but not meaningfully greater ($2459 vs $2271; P<.001). CONCLUSION: Hospitals providing medical education to pediatricians and safety net care do so without increasing LOS or cost of care for pediatric asthma. PMID- 11772194 TI - Pediatric violence-related injuries in Boston: results of a city-wide emergency department surveillance program. AB - CONTEXT: Violence-related injuries among children are common, but age-based incidence data are not easily available. OBJECTIVES: To describe injuries due to violence in a population-based case series of children and to estimate injury incidence. DESIGN: Prospective surveillance of children residing in Boston, Mass, who received pediatric emergency department treatment for violence-related injury during a 4-year period beginning April 15, 1995. SETTING: Pediatric emergency departments in Boston. PATIENTS: Children aged 3 through 18 years who came to a hospital emergency department between April 1995 and April 1999. Violence-related injuries were defined as those resulting from a situation of conflict involving 2 or more persons with intent to harm, as assessed by health care personnel caring for the patients. Self-inflicted injuries and injuries caused by child abuse (including any injury resulting from a conflict with a parent or guardian) were excluded. Homicides of Boston children aged 3 through 18 years who were killed during the study period were included based on police data. MAIN OUTCOME MEASURE: Population-based violence-related injury rates. RESULTS: There were 2035 injury related visits caused by violence, which reflects a rate of 52.7 (95% confidence interval, 50.5-54.9) per 10 000 person-years. Most injuries were relatively minor; 6.4% of visits resulted in admission. The youth violence-related injury rate in Boston declined at an average rate of 12% annually during the period studied. CONCLUSION: Pediatric emergency department monitoring of violence related injury in Boston suggests that childhood injuries due to violence declined during the late 1990s. PMID- 11772195 TI - Long-term consequences of Kawasaki disease among first-year junior high school students. AB - OBJECTIVE: To determine whether height, weight, and electrocardiographic (ECG) abnormalities differ at the age of 13 years between adolescents with and without Kawasaki disease (KD) (also known as mucocutaneous lymph node syndrome). DESIGN: A population-based cohort study. SETTING: School community and public health service. METHODS: Data from the nationwide surveys of KD in Japan were linked with those of junior high school cardiac screening in Tochigi Prefecture between April 1, 1986, and June 30, 1998 (except data for 1988 and 1994). Using this database, students with KD and students without KD in the first year of junior high school were compared. MAIN OUTCOME MEASURES: Height, weight, and ECG abnormalities. RESULTS: Eight hundred sixty students (486 adolescent boys and 374 adolescent girls) with KD and 308 729 students (158 193 adolescent boys and 150 536 adolescent girls) without KD were located. There was no difference in average height and weight between the students with and without KD (using the P values for a t test of the means). The proportion of abnormal ECG findings was 10% and 3% among those with and without KD, respectively. CONCLUSION: Even at age 13 years, the proportion of abnormal ECG findings was about 3 times higher among adolescents with KD (using a chi(2) test of the difference in 2 binomial proportions). PMID- 11772196 TI - Radiological case of the month. Bilateral congenital apical lung herniation. PMID- 11772197 TI - Pathological case of the month. Acute symptomatic hypercalcemia associated with ovarian small cell carcinoma. PMID- 11772198 TI - Hormone-containing hair product use in prepubertal children. PMID- 11772199 TI - Rates of missed appointments among pediatric patients in a private practice: Medicaid compared with private insurance. PMID- 11772200 TI - Exposure to possible risk is unethical. PMID- 11772201 TI - The choice by HIV-positive women to exclusively breastfeed should be supported. PMID- 11772203 TI - Reevaluating the efficacy of naturopathic ear drops. PMID- 11772208 TI - Quality care in surgery. PMID- 11772209 TI - The POSSUM system of surgical audit. PMID- 11772210 TI - The comparative assessment and improvement of quality of surgical care in the Department of Veterans Affairs. AB - Prompted by the need to assess comparatively the quality of surgical care in 133 Veterans Affairs (VA) hospitals, the Department of Veterans Affairs conducted the National VA Surgical Risk Study between October 1, 1991, and December 31, 1993, in 44 VA medical centers. The study developed and validated models for risk adjustment of 30-day morbidity and 30-day mortality after major surgery in 8 noncardiac surgical specialties. Similar models were developed for cardiac surgery by the VA's Continuous Improvement in Cardiac Surgery Program. Based on the results of the National VA Surgical Risk Study and the Continuous Improvement in Cardiac Surgery Program, the VA established in 1994 a VA National Surgical Quality Improvement Program (NSQIP), in which all the medical centers performing major surgery participated. An NSQIP nurse at each center oversees the prospective collection of data and their electronic transmission for analysis at 1 of 2 data coordinating centers. Feedback to the providers and managers is aimed at achieving continuous quality improvement. It consists of (1) comparative, site specific, and outcome-based annual reports; (2) periodic assessment of performance; (3) self-assessment tools; (4) structured site visits; and (5) dissemination of best practices. The NSQIP also provides an infrastructure to enable the VA investigators to query the database and produce scientific presentations and publications. Since the inception of the NSQIP data collection process, the 30-day postoperative mortality after major surgery in the VA has decreased by 27%, and the 30-day morbidity by 45%. The future of the NSQIP lies in expanding it to the private sector and in enhancing its capabilities by incorporating additional measures of outcome, structure, process, and cost. PMID- 11772211 TI - Quality improvement in cardiac care. AB - Quality improvement in cardiac care has made considerable progress over the past 30 years. During that period, there has been the development of multi institutional databases to monitor outcomes following cardiothoracic surgery. These databases initially began using only volume and unadjusted operative (30 day) mortality as outcome criteria. There has been a progressive increase in their sophistication, with the building of risk models based on preoperative variables, which accurately predict the risk of adverse outcomes. Other outcomes have been added including risk-adjusted mortality and morbidity; efficiency outcomes such as length of stay, quality of life, functional health status, neuropsychological outcomes; and long-term outcomes. PMID- 11772212 TI - APACHE 1978-2001: the development of a quality assurance system based on prognosis: milestones and personal reflections. PMID- 11772213 TI - Current concepts in nutritional assessment. PMID- 11772214 TI - Outcome report cards: a necessity in the health care market. AB - Measuring value (quality and cost) continues to be a major challenge in health care as providers respond to societal pressures (primarily from the payer) to standardize processes and patients assume the role of consumer. Relatively few studies report the extent to which report cards affect patient outcomes of care. Survey results indicate high levels of public distrust in report cards. The information that patients desire often is not what is reported because traditional indicators of quality often serve institutional needs rather than patient needs. Patients understand and value information framed as risk avoidance more so than as an opportunity for better health. Effective report cards are brief and simple. The model surgical report card for patients suggested herein includes ratings for patient satisfaction, functional status and well-being, specific symptom assessment, biologic indicators of disease progress, and costs. Successful report cards strike a balance between quality and cost that meets the needs of the stakeholder for whom they are intended. PMID- 11772215 TI - Quality measurement of outcome in general surgery revisited: commentary and proposal. AB - Surgery has been trying to catch up to evidence-based medicine. Assessment of outcome in surgery is the child for quality assurance of patient care. We surgeons have our own set of mental variables that can predict good and poor outcomes. We value our experience and that of others, yet, are always inquisitive about which best predict morbidity and mortality. We all have our own functional equations for outcome that varies qualitatively and quantitatively. The main problem is lack of a uniform mathematical equation for individual patient risk factors that we refer to because of the limitations inherent in the equation or our understanding and awareness. Reviewing the literature in surgical outcome measurement, the impression is one of increasingly diverse messages with conclusions that are institution dependent. This can initiate confusion and controversy when comparing outcomes or extrapolating to one's own practice while hindering training surgeons to contribute to the evolving evidence of objective quality measurement early in a career. Overall, we are falling behind in recognizing this evolving problem. In this article, I address this controversy and attempt to offer new avenues in achieving a consensus among us in patient risk-adjusted outcomes by adopting and modifying well-recognized risk scoring systems from either side of the Atlantic Ocean. The millennium should see the birth of a new generation of surgeons charged with evidence-based ideas in quality outcome measurement and ready to improve current mathematical models. PMID- 11772216 TI - Visceral artery pseudoaneurysms following pancreatoduodenectomy. AB - Pancreatic and biliary fistulas and delayed gastric emptying are the most common complications after pancreatoduodenectomy. The development and bleeding of visceral arterial pseudoaneurysms are rare phenomena and pose diagnostic and treatment dilemmas. We describe 5 recent patients who developed bleeding from visceral artery pseudoaneurysms after pancreatoduodenectomy. These patients all had "herald" bleeding from their abdominal drains. Subsequent angiography and therapeutic embolizations were successfully performed. PMID- 11772217 TI - To stent or not to stent bilioenteric anastomosis after iatrogenic injury: a dilemma not answered? AB - BACKGROUND: Bile duct injury is a complex and serious complication whose frequency has not diminished. A bilidigestive anastomosis (Roux-en-Y hepaticojejunostomy) is usually needed after complex injuries. Placement of an anastomotic stent is a matter of debate and to our knowledge there is no study that compares the results between stenting and not stenting the anastomosis. DESIGN: A retrospective review of medical records of patients operated on for biliary reconstruction after iatrogenic injury. SETTING: Tertiary care academic university hospital. PATIENTS: A comparative study was performed of patients operated on between 1995 and 1999, who were referred to our hospital for acute or elective reconstruction of the biliary tract following iatrogenic injury. All patients underwent Roux-en-Y hepaticojejunostomy. The patients were divided into 2 groups: those who underwent Roux-en-Y hepaticojejunostomy with a transanastomotic stent and those who underwent Roux-en-Y hepaticojejunostomy without a transanastomotic stent. MAIN OUTCOME MEASURES: Operative mortality, anastomotic dysfunction, biliary fistula, reoperations, postoperative complications, postoperative liver function tests. RESULTS: Sixty-three patients with high and complex biliary injuries (Bismuth type III, IV; Strasberg D, E). Thirty-seven cases had reconstruction with the placement of a transanastomotic stent and 26 did not have a stent placed. No operative mortality was observed. The postoperative outcomes of both groups were compared and no differences found. Good results were observed in more than 80% of the patients. Reoperations were more frequent in the nonstented group (15% vs. 5%) and complications were more frequent in the stented group (16% vs. 7%). CONCLUSIONS: Good results are obtained with a Roux-en-Y hepaticojejunostomy after complex injuries. The use of transanastomotic stents has to be selective according to the individual characteristics of each patient and the experience of each surgeon. We recommend their use when unhealthy (ie, ischemic, scarred) and small ducts (<4 mm) are found. PMID- 11772218 TI - Surgical indications in idiopathic splenomegaly. AB - HYPOTHESIS: The incidence of primary lymphoma of the spleen in patients with idiopathic splenomegaly is significant. DESIGN: Retrospective review of all patients referred to a general surgical service for splenectomy. SETTING: A large tertiary care hospital. PATIENTS: Between 1994 and 2001, 86 nontrauma patients were referred for splenectomy. Of these, 18 had idiopathic splenomegaly despite prior workup with computed tomography, peripheral smear, bone marrow biopsy, and laboratory testing. All patients were symptomatic and displayed varying degrees of cytopenia. INTERVENTION: All 18 patients underwent open splenectomy for diagnosis and treatment of their cytopenias. MAIN OUTCOME MEASURE: Incidence of lymphoma in the pathologic specimens. RESULTS: The mean size of the spleens was 21 cm (range, 14-34 cm) and mean weight was 996 g (range, 320-1840 g). In all 18 patients, the surgical specimen provided a diagnosis. Sarcoidosis was discovered in 4 patients, and 1 patient had Castleman disease. Six patients with the benign diagnosis of hypersplenism received no further interventions, and the cytopenias resolved in all 6 cases. The 7 remaining patients (39%) were diagnosed with lymphoma. Five had marginal zone lymphoma, and 2 had a more aggressive B-cell lymphoma. Three patients required chemotherapy, but 4 are still in remission since their splenectomies and show no evidence of active disease. The mean follow up was 20 months. CONCLUSIONS: A high percentage of patients with splenomegaly of unknown etiology will have primary lymphoma of the spleen. Splenectomy is both diagnostic and therapeutic and should be considered for all patients with idiopathic splenomegaly. PMID- 11772220 TI - Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. AB - BACKGROUND: Since 1995, we have been performing pancreatoduodenectomy with regional and para-aortic lymph node dissection for patients with distal bile duct cancer. Prognostic indicators after extended lymphadenectomy have not been fully understood. HYPOTHESIS: Pancreatoduodenectomy with extended lymphadenectomy and adjuvant chemotherapy is the treatment of choice for patients with distal bile duct cancer. DESIGN: In a retrospective study, univariate and multivariate models were used to analyze the effect of patient demographics, tumor characteristics, and treatment factors on long-term survival. SETTING: Oita Medical University and its affiliated hospitals in Japan. PATIENTS: From 1995 to 1999, 27 patients with distal bile duct cancer underwent pancreatoduodenectomy with extended lymphadenectomy. In 9 patients fluorouracil (500 mg/d) was infused continuously for 14 days after surgery as adjuvant chemotherapy. MAIN OUTCOME MEASURES: Clinicopathologic characteristics and long-term results. RESULTS: In 6 patients (22%) major surgical complications occurred including 1 in-hospital death (3.7%). For 26 patients, the survival rates were 65% for 1 year and 37% for 3 and 5 years. Univariate analysis found that the absence of lymph node metastasis, no more than 2 involved nodes, and negative resection margins were predictors of survival. Multivariate analysis with a Cox proportional hazards regression model revealed that favorable factors for survival included up to 2 positive nodes, negative resection margins, and the use of postoperative adjuvant chemotherapy. CONCLUSIONS: Patients with up to 2 positive lymph nodes had a more favorable prognosis than that of other patients. We recommend pancreatoduodenectomy with extended lymphadenectomy and adjuvant chemotherapy for the treatment of patients with distal bile duct cancer. PMID- 11772221 TI - Estradiol administration improves splanchnic perfusion following trauma hemorrhage and sepsis. AB - HYPOTHESIS: The female sex steroid 17beta-estradiol improves immune functions following trauma-hemorrhage in rodent models. Therefore, we hypothesized that 17beta-estradiol administration following trauma-hemorrhage would also improve cardiac output, splanchnic perfusion, and oxygen utilization, even after the induction of subsequent sepsis. SETTING: A university laboratory. INTERVENTION: Male rats underwent midline laparotomy (ie, soft tissue injury). They were bled to a mean arterial pressure of 35 to 40 mm Hg for 90 minutes and resuscitated over 60 minutes with lactated Ringer solution. At the beginning of resuscitation, 17beta-estradiol (l mg/kg) or a vehicle was administered. At 20 hours after resuscitation, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). MAIN OUTCOME MEASURES: At 5 hours after CLP, cardiac performance (via a left ventricular catheter), cardiac output, and organ blood flow were determined using strontium 85 microspheres. Blood samples were collected from the femoral artery and jugular, portal, and renal veins to determine systemic and regional oxygen delivery and consumption. Moreover, circulating levels of 17beta estradiol, its adrenal precursor dehydroepiandrosterone (DHEA), and corticosterone were assessed by enzyme-linked immunosorbent assay. RESULTS: Hemorrhage and subsequent sepsis significantly depressed cardiac performance, cardiac output, organ perfusion, and oxygen consumption. Estrogen did not restore cardiac output or systemic oxygen consumption; nonetheless, it restored the depressed intestinal perfusion. Rats treated with estrogen had significantly elevated levels of plasma 17beta-estradiol, but the levels of DHEA or corticosterone were not affected. CONCLUSIONS: The increase in gut perfusion could represent a potential mechanism for the salutary effects of 17beta estradiol following trauma-hemorrhage. Because 17beta-estradiol improves systemic and intestinal perfusion after trauma-hemorrhage and induction of subsequent sepsis, this agent appears to be a promising adjunct for the treatment of trauma victims. PMID- 11772222 TI - Islet yield remains a problem in islet autotransplantation. AB - For patients with chronic pancreatitis whose pain is inadequately controlled with opiate analgesia, surgical resection offers a good chance of symptomatic relief. However, the inevitable sequela is type 1 diabetes mellitus and its attendant long-term complications. Islet cell autotransplantation offers a theoretical "cure" for this iatrogenic diabetes but this end point has not been produced consistently in clinical practice. The main factor determining the likelihood of insulin independence after islet autotransplantation is the islet mass that is transplanted. This review examines the factors that affect the functional islet mass available for transplantation. Original articles and reviews from peer reviewed journals were analyzed following a computer search of the MEDLINE database from 1966 to the present, we extracted mainly level 2 and level 3 data. Although improvements in collagenase consistency and purification techniques and reductions in cold ischemic times have all been shown to improve islet yield, there is still the need to optimize every stage in the islet isolation process. Increasing the proportion of potential islets in the final isolate is of particular importance in chronic pancreatitis because the total mass of islets initially available in the gland might be just sufficient to produce insulin independence after islet autotransplantation. We believe that reducing the warm ischemic time might significantly increase the likelihood of insulin independence after islet autotransplantation. PMID- 11772223 TI - Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. AB - HYPOTHESIS: Intravenous patient-controlled analgesia (IV PCA) meperidine hydrochloride can be used with a reasonable margin of safety. DESIGN: A retrospective review was performed of 355 medical records of patients receiving IV PCA meperidine treatment. Four groups of patients were defined, based on daily meperidine dose and the presence or absence of central nervous system excitation adverse effects. Use of more than 600 mg/d of meperidine hydrochloride was considered a high dose. SETTING: University tertiary care hospital. PARTICIPANTS: Postoperative patients from general, orthopedic, neurosurgical, gynecological, and urologic procedures receiving IV PCA. INTERVENTIONS: If patients were judged to have consumed significant amounts of meperidine, the analgesic regimen was modified to (1) discontinue meperidine therapy, (2) substitute hydromorphone hydrochloride, or (3) decrease the use of meperidine by adding oral methadone hydrochloride or transdermal fentanyl citrate to the regimen. MAIN OUTCOME MEASURES: Patients who received less than 10 mg/kg per day of IV PCA meperidine hydrochloride therapy were unlikely to experience central nervous system excitatory adverse effects and maintain adequate analgesia. RESULTS: The mean meperidine hydrochloride consumption for those patients classified as high dose, asymptomatic was 13.3 mg/kg per day (95% confidence interval, 12.1-14.4 mg/kg per day). This differed statistically significantly (P<.05) from the mean meperidine hydrochloride dose in patients classified as high dose, symptomatic, which was 16.9 mg/kg per day (95% confidence interval, 14.7-19.2 mg/kg per day). The duration of meperidine use did not differ among the 4 patient groups. The incidence of a central nervous system toxic reaction associated with IV PCA meperidine therapy was 2%. CONCLUSIONS: We recommend 10 mg/kg per day as a maximum safe meperidine hydrochloride dose by an IV PCA device for no longer than 3 days. Daily patient evaluation is mandatory. Care must also be taken when using this dose to ensure the absence of renal dysfunction or enhanced hepatic metabolism of meperidine. PMID- 11772224 TI - The value of partial splenic autotransplantation in patients with portal hypertension: a prospective randomized study. AB - HYPOTHESIS: Splenic autotransplantation plays a role in preserving immune function of the spleen in patients with portal hypertension and liver cirrhosis. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENTS: Twenty patients (19 men and 1 woman; aged 33-80 years) suffering from portal hypertension and liver cirrhosis were randomly allocated into 2 groups. Each group consisted of 10 patients. INTERVENTIONS: All patients underwent modified Sugiura operation. In the control group, splenectomy was performed, while partial splenic autotransplantation into the retroperitoneal space was additionally completed in the splenic autotransplantation group. MAIN OUTCOME MEASURES: Serum tuftsin and IgM were measured preoperatively and 2 months after surgery. Dynamic scintigraphy with technetium Tc 99m-labeled heat-damaged erythrocytes was performed at 2-month intervals during the 8-month follow-up. RESULTS: There was no statistical difference in the mortality of the groups. The preoperative levels of serum tuftsin and IgM showed no statistical difference between groups. However, although these measures had decreased remarkably in the control group 2 months after operation (P<.001 for serum tuftsin; P =.04 for serum IgM), they remained stable in the splenic autotransplantation group (P =.25 for serum tuftsin; P =.12 for serum IgM). Four patients within the splenic autotransplantation group showed positive scanning of the transplanted splenic fragment during follow-up, whereas there was no positive scanning in the control group. CONCLUSION: Our results suggest that partial splenic autotransplantation can preserve immune function of the spleen, as measured by serum levels of tuftsin and IgM, in patients with portal hypertension and liver cirrhosis. PMID- 11772225 TI - Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics. AB - HYPOTHESIS: Surgical margin, i.e., the area of possible local intrahepatic metastasis, is controversial in hepatectomy for hepatocellular carcinoma. DESIGN: The blood drainage area of tumor was identified preoperatively by abdominal helical computed tomographic scan under hepatic arteriography and excised as surgical margin. The specimens were pathologically examined on the basis of the corresponding computed tomographic images. SETTING: University hospital. PATIENTS: From June 2, 1997, to April 24, 2000, 67 patients with hepatocellular carcinoma who underwent curative hepatic resection. MAIN OUTCOME MEASURE: Intrahepatic recurrence. RESULTS: Blood drainage area of tumor could be classified into the following types. The marginal type (drainage into the peritumorous area) was frequent (50 cases) and excised mostly by nonanatomic, limited resection. Portal vein type (drainage into the portal branches) was less common (12 cases) and resected mostly by anatomically systematic hepatectomy. The remaining 5 cases were of the hypovascular type and underwent limited resection. Multiple nodules were frequently found inside the drainage area (4 of 8 cases) and were moderate or poorly differentiated hepatocellular carcinoma, consistent with intrahepatic metastasis. Solitary nodules were mostly outside the drainage area (11 of 12 cases) and contained well-differentiated hepatocellular carcinoma (7 of 10 cases), suggesting multicentric carcinogenesis. Intrahepatic recurrences were commonly found in bilateral or contralateral lobes (17 of 19 cases) and divided into 2 groups with a few (< or =4) and multiple (> or =8) recurrent nodules. CONCLUSIONS: Surgical margin varied according to tumor hemodynamics. Tumor recurrences may result not only from multicentric carcinogenesis but also from intrahepatic metastasis via systemic circulation. PMID- 11772226 TI - A 1-stage surgical treatment for postherniorrhaphy neuropathic pain: triple neurectomy and proximal end implantation without mobilization of the cord. AB - BACKGROUND: The recommended surgical treatment for chronic neuropathic pain after herniorrhaphy has been a 2-stage operation including: (1) ilioinguinal and iliohypogastric neurectomies through an inguinal approach and (2) genital nerve neurectomy through a flank approach. HYPOTHESIS: A 1-stage surgical procedure resecting all 3 nerves from an anterior approach avoids a second operation through the flank and successfully treats chronic neuralgia. SETTING: A private practice dedicated to abdominal wall hernia surgery in general community hospitals. PATIENTS: Between 1995 and 2001, 49 patients underwent triple neurectomies with proximal end implantation to treat chronic postherniorrhaphy neuralgia. INTERVENTION: Triple neurectomy of the ilioinguinal, iliohypogastric, and genital nerves performed under local anesthesia with implantation of their proximal ends and without mobilization of the spermatic cord. RESULTS: Two patients (4%) reported no improvement. Eighty percent of patients recovered completely, and 16% had transient insignificant pain with no functional impairment. These results are comparable to the results of the 2-stage operation. CONCLUSIONS: Simultaneous neurectomy of the ilioinguinal, iliohypogastric, and genital nerves without mobilization of the spermatic cord is an effective 1-stage procedure to treat postherniorrhaphy neuralgia. It is performed under local anesthesia and avoids testicular complications. Proximal end implantation of the nerves prevents adherence of the cut ends to the aponeurotic structure of the groin, which can result in recurrence of the pain. PMID- 11772228 TI - Modified radical mastectomy with knife technique. AB - Infusion of the breast with a tumescent solution of dilute epinephrine hydrochloride in lactated Ringer solution in patients undergoing modified radical mastectomy allows the procedure to be performed rapidly with scalpel dissection and minimal blood loss. The classic technique of modified radical mastectomy with addition of the tumescent solution is described herein. PMID- 11772229 TI - Special feature: image of the month. Sweet syndrome. PMID- 11772230 TI - Moments in surgical history: Ferdinand Campbell Stewart's surgical travel guide. PMID- 11772231 TI - Conventional cytotoxic and novel therapeutic concepts in colorectal cancer. AB - Colorectal cancer (CRC) is a major cause of death, particularly in the Western world, leading to 400,000 deaths each year. Of the patients, 30% have advanced disease at presentation, either locally or at distant sites and chemotherapy in this setting has an established role in improving survival and palliating symptoms. In addition, approximately 50% of those patients initially believed to be cured by surgery, subsequently relapse and die of their disease. Adjuvant chemotherapy administered for six months after surgery for Dukes C colon cancer improves absolute survival by 5-10%. However, the role of adjuvant chemotherapy in Dukes B colon or Dukes B/C rectal tumours is still controversial and is only recommended within the scope of a randomised clinical trial. Cytotoxic drug development for colorectal cancer has traditionally followed the established pathway of Phase I, Phase II and then Phase III trials in advanced disease, with subsequent translation into the adjuvant setting. For the purpose of this review current conventional chemotherapy for advanced CRC is described, followed by an explanation of newer developments that are predicated upon our increasing understanding of the molecular processes underpinning malignant transformation, invasion and metastasis. Paradigm shifts in trial design necessitated by a mechanistic approach to drug development are also discussed. PMID- 11772232 TI - Innovative treatments for non-small cell lung cancer. AB - Lung cancer remains the most frequent and most lethal cancer worldwide. Non-small cell lung cancer (NSCLC) comprises the vast majority of the histological types. Surgery remains the standard therapy for early stage disease but for advanced stage disease, modern treatment is unsatisfactory. However, during the past ten years, improvements in response and survival have been seen with the use of newer chemotherapy regimens. Early studies of neo-adjuvant (pre-operative) chemotherapy for resectable stage III patients have shown promising results. For patients with non-resectable NSCLC platinum-based doublets are now established as first-line treatment, either alone or in combination with radiotherapy. Innovative non platinum based combinations are actively being evaluated. The most promising non platinum agents at this time include gemcitabine, paclitaxel, docetaxel, irinotecan and vinorelbine. These agents appear to be effective as single agents and in combinations and also have improved toxicity profiles. Several other systemic approaches are under active evaluation; the most promising areas include anti-angiogenesis agents, immunotoxins, interleukins, vaccines and molecular therapy. PMID- 11772233 TI - Novel therapies for renal cell carcinoma. AB - Metastatic renal cell cancer remains a disease which is difficult to treat medically. Prognosis often depends more on intrinsic disease features than on treatment choices. In this review, we examine novel therapies and scientific directions surrounding the RCC treatment problem. Reports relating chromosomal aberrations and of comparative gene expression analyses relating to RCC, are reviewed briefly. The central role of the von Hippel Lindau protein in clear cell RCC pathogenesis is evident. The limited contribution of conventional cytotoxic chemotherapy is mentioned. Some clinically applied agents whose clinical results are highlighted include 5-FU, retinoids, thalidomide, razoxane and IL-12. Features of the pathophysiology of von Hippel Lindau protein are described, with attention to potential novel therapies targeting HIF-1alpha, VEGF, TGF-beta1 and TGF-alpha pathways. Immunotherapy is being explored in many angles. Most basic are cytokine therapies incorporating new IL-2 and IFN-alpha schedules. Newer cytokine-based drugs include pegylated forms and IL-12. Allogeneic mini transplantation has generated much interest. Tumour-associated antigens are being used to direct therapy using both identified and non-identified epitopes. A variety of tumour-cell vaccine and dendritic-cell vaccine clinical approaches are discussed. Finally, nephrectomy for known metastatic disease has been demonstrated to be helpful in retrospective and now prospective trials. Resection of metastases is also discussed. We are optimistic that the further clinical development among these novel therapies will improve the outlook for metastatic RCC. PMID- 11772234 TI - Liposomal cancer chemotherapy: current clinical applications and future prospects. PMID- 11772235 TI - Peptides as receptor ligand drugs and their relationship to G-coupled signal transduction. AB - Peptides act as effector agents that regulate and/or mediate physiological processes, serving as hormones, neurotransmitters and signal transducing factors. The low molecular weight peptides affect receptor-mediated events, which influence cardiovascular, gastrointestinal and neurocranial systems. While some peptides have been marketed as drugs, many have served as leads or templates for the development of non-peptide drugs that mimic peptide actions. This review presents the advantages and disadvantages of using peptides as drugs that bind as ligands to cell-surface receptors and considers their applications in such events. The value of both the peptides and their mimics is based on their participation in the biomodulation of physiological processes, which frequently employ scaffolding proteins acting in a cascading sequence of protein-to-protein interactions. The peptides bind to G-coupled surface receptors to initiate a signal that is transduced to the interior of the cell through multiple layers of phosphorylating enzymes and binding proteins. Peptides have been further employed to identify the molecular targets of signal transduction, the uncoupling of which might provide a means for various disease therapies. The exploitation of such peptide-mediated signal pathways, which are of primary importance to tumour cells, may provide an attractive strategy for anticancer therapy in the future. PMID- 11772237 TI - Phosphoinositide 3-kinase inhibition in cancer treatment. AB - Over the past ten years, our knowledge of the integral role that the phospho inositide 3-kinases (PI3Ks) and their 3'-phosphorylated lipid products (3' phosphorylated phosphoinositides; 3P-PIs) play in the mediation of signal transduction, cytoskeletal rearrangements and membrane trafficking has expanded considerably. They are now known to be involved in the regulation of cell growth, differentiation, mobility, proliferation and survival and hence they have become a potential target for the control of the growth and spread of cancer cells. More recently, the correlation of the multiplicity of isomers (both catalytic and regulatory) within the different classes of the PI3Ks with their functional relevance has become possible. This, combined with our further understanding of the protein recognition patterns for their different 3P-PIs and the newly described pathways in the control of the levels of these by dephosphorylation, has provided new aspects and areas for interference in these multiple PI3K signalling pathways. However, in the search for effective, non-toxic, drugs for use in the treatment of cancers, these individual targets for PI3K inhibition need to be further correlated with the specific in vivo effects on cell survival, invasivity and metastatic potential. Here, the range of PI3K inhibition targets are discussed in the light of recent experimental findings, with a view to the exploitation of their specificities in new approaches to effective cancer treatments based on PI3K activity inhibition. PMID- 11772236 TI - Induction of tumour cell apoptosis by matrix metalloproteinase inhibitors: new tricks from a (not so) old drug. AB - Matrix metalloproteinases (MMPs) regulate the turnover of extracellular matrix (ECM) components and play an important role in embryo development, morphogenesis and tissue remodelling, as well as in tumour invasion and metastasis. Synthetic MMP inhibitors (MMPIs) were designed to prevent tumour cell-induced changes in ECM and thereby achieve antitumour activity. Several MMPIs have entered clinical trials but the preliminary results did not meet the expectations. Recent evidence suggests that MMPs may have more diverse roles than originally believed, influencing angiogenesis, cytokine secretion, as well as tumour cell growth and survival. In particular, synthetic MMPIs may directly induce apoptosis of cancer cells via their inhibitory effect on the shedding of Fas Ligand (FasL), a transmembrane member of the TNF superfamily that kills susceptible cells through its receptor, Fas. Several types of cancers have been shown to express FasL and to shed it from their surface as a soluble form, which is significantly less potent in promoting apoptosis. MMP-7 was recently reported to catalyse this process. Conversely, inhibition of FasL-shedding by a synthetic MMPI results in apoptosis of Fas-sensitive cancer cells. More importantly, DNA-damaging anticancer agents, such as adriamycin, kill cancer cells, at least in part, by upregulating FasL. By inhibiting the proteolytic cleavage of FasL, MMPIs can potentiate the killing effect of traditional chemotherapeutic drugs. These studies therefore demonstrate a direct link between DNA-damaging chemotherapeutic drugs, the apoptosis-inducing Fas/FasL system and the proteolytic activity of MMPs and have important therapeutic implications. For example, the proteolytic activity of MMP-7, which is broadly expressed in primary and especially metastatic human malignancies, may contribute to tumour resistance to cytotoxic agents; targeting and inactivating MMP-7 may, therefore, enhance the efficacy of conventional cancer chemotherapy. PMID- 11772238 TI - Molecular biology and cellular physiology of refractoriness to androgen ablation therapy in advanced prostate cancer. AB - We review the extensive body of data on the molecular aetiology of hormone refractory disease in metastatic prostate cancer patients. Particular emphasis is placed on the crucial role of the bone micro-environment, especially the intercellular interactions of metastatic prostate cancer cells and osteoblasts in promoting the establishment of hormone refractory disease. Resistance of tumour cells to anticancer therapies is generally viewed as a phenomenon almost exclusively determined by chromosomal defects and/or gene mutations. However, it is now well-documented that the local milieu of the bone metastases can also protect tumour cells from anticancer therapy- induced apoptosis, either independently or synergistically with resistance-related genetic alterations. A key determinant of this protection is the urokinase/plasmin cascade which modulates the local concentration of survival factors, such as insulin-like growth factor (IGF-1). The molecular pathways whereby this major growth and survival factor for prostate cancer cells exerts its anti-apoptotic effect on prostate cancer cells are discussed. PMID- 11772239 TI - Novel approaches in the treatment of lupus nephritis. AB - In systemic lupus erythematosus hyperactive helper T-cells drive polyclonal B cell activation and secretion of pathogenic auto-antibodies. The auto-antibodies form immune complexes with their respective auto-antigens, which in turn deposit in sites such as the kidney and initiate a destructive inflammatory reaction. Lupus nephritis can be managed successfully in the majority of cases; however, the most widely used immunosuppressive therapies, notably corticosteroids and cyclophosphamide are non-specific and are associated with substantial toxicities. Novel treatments for lupus nephritis have to be at least as effective and less toxic than existing therapies. The ultimate aim is to develop treatments that target specific steps in the disease process. Novel therapeutic strategies in the short-term more likely will focus on refining regimens of drugs that are already in use (mycophenolate mofetil, adenosine analogues) and combinations of existing chemotherapeutic agents, as well as attempts to achieve immunological reconstitution using immunoablative chemotherapy with or without haematopoietic stem cell rescue. Several new agents targeting specific steps in the pathogenesis of lupus are in various phases of clinical development. Interrupting the interactions between T-lymphocytes and other cells by blocking co-stimulatory molecules, such as CD40 ligand or CTLA4-Ig, may interfere with the early steps of pathogenesis. Blocking IL-10 may decrease auto-antibody production and help normalise T-cell function. Treating patients with DNase or interfering with the complement cascade by blocking C5, or neutralising pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiotype antibodies may prevent immune complex formation and/or deposition. PMID- 11772240 TI - Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators. AB - CGRP is a potent vasodilator that has been shown to have a physiological and/or pathological role in neurogenic inflammation, headaches including migraine, thermal injury, circulatory shock, pregnancy and menopause, hypertension and heart failure and is known to be cardioprotective. CGRP is also a positive inotrope and increases heart rate. Clinical trials have shown beneficial effects of the vasodilatory action of CGRP in hypertension, angina, heart failure, Raynaud's disease and venous stasis ulcers. However, the clinical potential of CGRP is limited as it has to be given by infusion and is quickly broken down. Oral long acting CGRP-mimetics may have potential in disorders in which CGRP has been shown to be beneficial. CGRP-mimetics include capsaicin/vanilloid receptor agonists and gene transfer of an adenoviral vector that encodes prepro-CGRP. CGRP inhibitors have therapeutic potential in conditions in which excessive CGRP mediated vasodilatation is present; neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock and flushing in menopause. CGRP inhibitors include capsaicin, antagonists at capsaicin/vanilloid receptors, civamide, CGRP receptor antagonists and 5-HT1D-receptor agonists. Drugs that are 5-HT1D-receptor agonists, the 'triptans' are already commonly used in migraine and the first small molecule CGRP antagonist, BIBN4096BS, is under clinical investigation for the treatment of migraine. PMID- 11772241 TI - Aminolevulinic acid: pharmacological profile and clinical indication. AB - The role of aminolevulinic acid hydrochloride (ALA) in photodynamic therapy (PDT) of in situ neoplasias and tumours of epithelial tumours is steadily increasing and it has been shown to be the drug with most clinical use in PDT. In dermatology, topical PDT with ALA is already postulated to be the treatment of choice for actinic keratoses and superficial basal cell carcinomas. In gastroenterology, pulmonology, uro- and nephrology, neurology and gynaecology ALA has an important role as a photosensitiser not only in the diagnosis of neoplastic tissue but as therapy; first experiences have been made with PDT in these organs. Besides the therapeutic efficacy of this technique, the fluorescence of ALA-induced porphyrins can be effectively used to detect and delineate epithelial and endothelial neoplasms. In dermatology, other indications for ALA-treatment are non-tumoural applications, especially psoriasis, viral induced diseases, or acne vulgaris. ALA is an effective compound in the diagnosis or therapy of various epithelial and endothelial neoplastic lesions. PMID- 11772242 TI - Ertapenem: a new carbapenem. AB - Ertapenem is a new 1-beta-methyl carbapenem, stable to dehydropeptidase, which binds preferable to penicillin-binding proteins (PBP) 2 and 3. Ertapenem has a broad antibacterial spectrum with MIC90 values < 0.5 mg/l for penicillin susceptible Streptococcus pneumoniae, Streptococcus pyogenes, methicillin sensitive Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Serratia spp., Proteus spp., Clostridium perfringens, Fusobacterium spp. Peptostreptococcus spp. and anaerobic Streptococcus spp. Ertapenem exhibits a bactericidal mode of action as shown by time-killing curves and exhibits a short PAE of 1.4 - 2.6 h against the Gram positive strains but no PAE against Gram-negative strains. In an infection model in mice, it has been shown that ertapenem and imipenem were highly efficacious at a level of 2 mg/kg in bacterial clearance in comparison to ceftriaxone, cefepime, ceftazidime, cefazolin, cefonicid, cefotaxime and meropenem. In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 h and is developed as a single daily dose carbapenem. The protein binding is dose dependent and is estimated to 94% at concentrations under 100 mg/l and approximately 85% at 300 mg/l. Cmax after a dose of 1 g in healthy volunteers has been estimated to 190 mg/l. Given the pharmacokinetic/pharmacodynamic data, it may be predicted that ertapenem will have an effect on most Gram-positive and Gram-negative bacteria with the exception of Pseudomonas aeruginosa, Enterococcus spp. and Acinetobacter spp. For pathogens with a MIC of 0.5 mg/l, the estimated T > MIC will be 50% (of 24 h) and for pathogens with a MIC of 1 mg/l 31%. For anaerobic bacteria with MIC values between 1-2 mg/l, the T > MIC may not be sufficient for bacterial eradication. However, clinical trials have to confirm this hypothesis. PMID- 11772243 TI - New developments in the treatment of ovarian cancer. AB - Ovarian cancer accounts for about 4% of all cancers in women in the United States, with over 23,000 cases diagnosed annually. Since patients often present with non-specific symptoms, diagnosis is generally made when disease has spread to the peritoneal cavity. Multi-modality therapy is established as the standard approach to treatment. Surgery remains a cornerstone of therapy for diagnosis, staging and treatment. Almost all patients receive some form of chemotherapy, either in the adjuvant setting or for locally advanced or advanced disease. The treatment of ovarian cancer has rapidly evolved in the past decade. Starting with the initial observation that alkylating agents were active in the treatment of this disease, new classes of agents have been rapidly incorporated in the therapeutic armamentarium. This has included the platinum compounds, taxanes and most recently, camptothecin derivatives, inhibitors of topoisomerase I. Much of the recent clinical research has revolved around how to incorporate these agents with surgery. PMID- 11772244 TI - ICE/Caspase-1 inhibitors as novel anti-inflammatory drugs. AB - In recent years, several strategies that selectively inhibit pro-inflammatory cytokines, have yielded effective protein-based therapies for inflammatory disorders, validating the therapeutic hypothesis that intervention in cytokine signalling can provide clinical benefit. However, these protein-based products must be administered by injection, a constraint associated with inconvenience, adverse effects and expense for patients, caregivers and insurers. Besides interfering with the effects of cytokines such as TNF-alpha or IL-1beta that have already been produced, inhibition of pro-inflammatory cytokine production or signalling with low-molecular weight orally-active drugs would combine the convenience of conventional pharmaceuticals with the focused efficacy of the protein therapies. Reducing IL-1beta and IL-18 production by inhibition of IL 1beta converting enzyme (ICE, caspase-1) is one promising strategy because of the key roles of these cytokines in many inflammatory diseases. Pralnacasan, the first orally available, potent and selective ICE inhibitor to enter clinical trials, is currently under investigation in rheumatoid arthritis. PMID- 11772245 TI - Irritable bowel syndrome: an update on therapeutic modalities. AB - Irritable bowel syndrome (IBS) is the most common condition that a physician faces in the GI clinic. Of the general population, 10 - 25% suffer from symptoms judged to be IBS. The negative impact of this disease includes not only pain, suffering and direct medical expenses but also significant social and job-related consequences. IBS can be the result of dysfunction in any part of the brain-gut axis: alterations in the CNS caused by psychological or other factors, abnormal gastrointestinal motility, or heightened visceral sensations. Diagnosis is based on either the Manning or Rome-II criteria. Education, reassurance and emotional support are the cornerstones of successful treatment. The mainstays of the current therapeutic approach continue to be: stress management strategies, dietary modification entailing addition of dietary fibre and pharmacotherapy. Pharmacotherapy is still limited to treating symptoms. Newer drugs that modulate motility or drugs that modulate visceral sensation may be useful in selected cases. Psychopharmacological agents are useful in the treatment of IBS, especially in those with psychological co-morbidity. Alternative therapies such as homeopathy, acupuncture, special diets, herbal medication and several forms of psychological treatments and hypnotherapy are sought by many patients and are now being offered by physicians as treatment options, either alone or in conjunction with conventional forms of therapy in patients with refractory symptoms. PMID- 11772246 TI - Novel therapies in the treatment of ulcerative colitis. AB - Ulcerative colitis is a chronic inflammatory disease of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. The progress in the fields of genetics and immunology has afforded important advances in our understanding of the inflammatory process. Traditional therapy with non-specific anti-inflammatories for ulcerative colitis remains our gold standard as newer targeted therapies have failed to provide any improved efficacy. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities. PMID- 11772247 TI - Helicobacter pylori: strategies for treatment. AB - Helicobacter pylori (Hp) is a Gram-negative bacteria able to live in the human stomach, a very surprising fact considering the acid environment of gastric mucosa. Identified by Marshall and Warren in 1982 [1,2], this bacterium seems aetiologically related to many gastric diseases, previously known as 'acid related diseases'. Compelling evidence demonstrates that Hp is the most important aetiological agent of gastritis [3], the principal causal factor in peptic ulcer [4], contributes to the genesis of gastric cancer [5] and has a critical role in the development of many mucosa-associated lymphoid tissue (MALT) lymphomas [6]. Although experimental data have recently provided hard evidence to support the role of Hp in the genesis of gastritis, ulcer and carcinoma [7], a critical argument for Hp generating peptic ulcer disease has been, in fact, the change in the natural history of peptic ulcer that follows the cure of the infection. PMID- 11772248 TI - The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent. AB - The dihydroxy bile acid, ursodeoxycholic acid (UDCA), has been in widespread clinical use in the Western world since the mid 1980s, when it was initially used for gallstone dissolution [1,2] and subsequently for the treatment of chronic cholestatic liver diseases [3,4]. Many clinical trials of UDCA in a variety of cholestatic disorders established biochemical and clinical improvements, and most importantly showed a significant prolongation of transplant-free survival after four years of treatment with UDCA in patients with primary biliary cirrhosis [5]. Despite its clinical efficacy, the precise mechanism(s) by which UDCA improves liver function during cholestasis is still a matter of debate [6]. It was initially considered that the choleretic effect of UDCA, coupled with its ability to cause a marked shift in the composition of the bile acid pool towards hydrophilicity, accounted for its mechanism of action. In recent years, however, it has become evident that UDCA and its conjugated derivatives are capable of exerting direct effects at the cellular, subcellular, and molecular levels by stabilising cell membranes, affecting signal transduction pathways, and regulating immune responses. In addition, we have shown that UDCA plays a unique role in modulating the apoptotic threshold in both hepatic and non-hepatic cells [7-10]. The purpose of this article is to examine the mechanism(s) by which UDCA prevents apoptotic cell death associated with cholestasis. In addition, we will also review a potentially novel and, heretofore, unrecognised role of UDCA as a therapeutic agent in the treatment of non-liver diseases associated with increased levels of apoptosis as a pathogenesis of the disorder. PMID- 11772249 TI - Development of agents for the treatment of systemic sclerosis. AB - Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised clinically by fibrosis and ischaemic atrophy. Internal organ involvement can be life-threatening. Although there are effective treatments for some of the organ based manifestations of SSc, for example proton-pump inhibitors for upper gastrointestinal disease, no drug has so far been proven to modify the underlying disease process. Our increased understanding of the pathogenesis of SSc, which involves a complex interplay between excessive collagen production, vascular abnormalities and immune dysfunction, is directing development of drugs which hold promise as 'disease-modifying' agents. Some of the drugs under investigation for the treatment of SSc have already been used in other conditions which 'overlap' with SSc, for example primary pulmonary hypertension. Conversely, it is to be hoped that in the future, drugs shown to be effective in SSc might prove beneficial for other fibrotic diseases. PMID- 11772250 TI - Recent advances in the management of adult myositis. AB - Standard drug therapy of adult polymyositis, dermatomyositis and inclusion body myositis includes high-dose corticosteroids and cytotoxic drugs (methotrexate, azathioprine (AZA) and cyclophosphamide). Recent data are in favour of the early introduction of a cytotoxic or immunomodulating drug in addition to corticosteroid therapy. In patients with corticosteroid- and cytotoxic-resistant myositis, promising novel approaches to management include: iv. megadose pulse methylprednisolone combined with cytotoxic drugs, combination therapy with both methotrexate and AZA, cyclosporin, tacrolimus, fludarabine and iv. immunoglobulin (IVIG). Recent advances in the understanding of the role of cytokines and complement, in the pathogenesis of myositis, have led to preliminary therapeutic trials of three biological agents: etanercept, infliximab and anti-C5 monoclonal antibody. PMID- 11772251 TI - Novel therapies in vasculitis. AB - The vasculitides comprise various clinical and pathological entities which pose a therapeutic challenge in terms of disease control versus drug toxicity. Glucocorticoids are important in most regimens; duration of exposure and dosages can be minimised by the use of cytotoxic drugs and transplant immunosuppressives such as cyclosporin, tacrolimus and mycophenolate mofetil. Among alkylating agents, cyclophosphamide has proven to be highly effective; switching to less toxic antimetabolites, typically methotrexate, for maintenance after achieving disease control is an effective strategy. Plasmapheresis may be considered when pharmacological options are maximised. IVIG infusions are of proven benefit in Kawasaki disease and possible benefit in other vasculitides. Targeting infective aetiologies is the basis of therapies such as lamivudine and vidarabine for hepatitis B associated polyarteritis nodosa as well as ribavarin and IFN-alpha for hepatitis C associated cryoglobinaemic vasculitis. IFN-alpha also has immunomodulatory effect even in non-hepatitis C-associated vasculitis. Trimethoprim-sulphamethoxazole has been used in limited Wegener's granulomatosis. Thalidomide, colchicine and dapsone are miscellaneous agents that have been used in Behcet's disease and cutaneous vasculitis. Anti-lymphocytic monoclonal antibodies have been employed for induction therapy in Wegener's granulomatosis. The tumour necrosis factor inhibitor etanercept is just being explored as a therapeutic agent. Bone marrow and stem cell transplantation may find a role in refractory disease. PMID- 11772252 TI - Therapeutic potential of endothelin receptor antagonists and nitric oxide donors in pulmonary hypertension. AB - Pulmonary hypertension can occur idiopathically as a primary disorder of the pulmonary circulation or more commonly, it can exist as a haemodynamic manifestation of a wide variety of pulmonary and cardiovascular diseases, including acute lung injury, chronic obstructive lung disease, congenital heart disease, mitral stenosis, chronic left-sided congestive heart failure and connective tissue diseases such as scleroderma. Pulmonary hypertension is associated with changes in vascular tone as well as vascular structure, with the relative contribution of each dependent upon the aetiology of the increased pulmonary vascular resistance. Most currently available treatments utilise anticoagulants as well as vasodilator drugs that only attenuate the vasoconstrictive component of the disease. The latter category includes oral calcium channel blockers, iv. and aerosolised prostacyclin analogues and inhaled nitric oxide but all three classes of vasodilators have disadvantages and limitations. Treatment with vasodilators is often ineffective in patients with longstanding pulmonary hypertension in which structural changes contribute significantly to the pulmonary hypertension, blood flow obstruction and right heart failure. In view of the immense clinical need, new therapies are being developed by pharmaceutical companies to treat pulmonary hypertension. This update will focus on the current development status of endothelin receptor antagonists and nitric oxide donors for the treatment of pulmonary hypertension. PMID- 11772253 TI - Anticoagulant therapy for osteonecrosis associated with heritable hypofibrinolysis and thrombophilia. AB - Osteonecrosis develops as the end-result of reduced blood flow to the femoral head. We postulate that venous thrombosis leads to increased intraosseus venous pressure, reduced arterial flow and hypoxic bone death. Hypofibrinolysis (reduced ability to lyse thrombi) and thrombophilia (increased tendency to form thrombi) appear to play an important role in osteonecrosis. If coagulation disorders cause osteonecrosis, then anticoagulation might ameliorate osteonecrosis. In subjects with coagulation disorders and osteonecrosis of the hip, provided that anticoagulant therapy is started before irreversible segmental collapse of the head of the femur, osteonecrosis may be arrested or, speculatively, sometimes reversed. This has the potential of preventing femoral head collapse which usually leads to total hip replacement. PMID- 11772254 TI - Therapeutic potential of COX-2 inhibitors in arthritis. AB - Arthritis and related musculoskeletal conditions occur with great frequency in the population world wide, causing significant morbidity and, in some instances, increased mortality. Affecting both the young and the old, 15% of the population in the US was estimated in 1995 to have some form of arthritis with an increase to 18% projected by the year 2020 [1]. The economic impact of arthritis and related disorders in the US alone was estimated to be 194.4 billion US dollars in 1992 and future costs are virtually certain to increase given the chronic nature of these diseases, their expanding prevalence and the considerable expense associated with newer therapies [2]. With no cure presently available, the aim of current treatment is to reduce inflammation, ameliorate symptoms and improve functional capacity. Non-steroidal anti-inflammatory drugs (NSAIDs), which suppress the formation of pro-inflammatory prostaglandins by antagonising the action of cyclooxygenase (COX), have been the mainstay of arthritis treatment for hundreds, if not, thousands of years. The clinical use of NSAIDs, however, has long been associated with significant toxicity. The recognition of two COX isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), both suppressed by traditional NSAIDs, has led to an expanded hypothesis of NSAID action which consists of two postulates, namely, the efficacy of NSAIDs in the treatment of arthritis is due to the suppression of COX-2, while much of the toxicity associated with non-selective NSAIDs is the consequence of COX-1 suppression. The emergence of agents which selectively inhibit COX-2 has made it possible to clinically evaluate the validity of each of these postulates. In this report, the published experience with selective COX-2 inhibitors in the treatment of mechanical and inflammatory arthropathies is reviewed to examine the premise that isolated COX-2 suppression is comparable in efficacy to the dual COX-1/COX-2 suppression produced by non-selective NSAIDs. PMID- 11772255 TI - Src inhibitors: genomics to therapeutics. AB - Following the milestone discoveries that identified Src as the first known protein tyrosine kinase and as a prototype oncogene, as well as Src transgenic studies to validate it as a promising therapeutic target for osteoporosis, intense efforts are being made to create Src inhibitor drugs. Drug discovery strategies focused on both the non-catalytic and catalytic domains of Src have successfully resulted in promising Src inhibitor lead compounds with potential therapeutic applications for osteoporosis, cancer, and other diseases. Some noteworthy examples of Src inhibitors are described, and their chemical diversity, structure-based design, and biological activities in vitro and in vivo are illustrated. The potency, selectivity, and in vivo efficacy of key Src inhibitors are being investigated in molecular, cellular and animal models. Consequently, Src inhibitor drug development is imminent, and current studies are well-poised to achieve the ultimate milestone of a Src inhibitor therapeutic. PMID- 11772256 TI - Peripheral channelopathies as targets for potassium channel openers. AB - Potassium channel openers (KCOs) are important tools that are often used to gain a greater understanding of K(+) channels. Agents that can induce or maintain the opening of K(+) channels also offer a therapeutic approach to controlling of cell excitability and offer a means of producing stability in biological systems. The pathogenesis of a broad range of peripheral disorders (e.g., LQT syndrome, hypokalemic periodic paralysis, hyperinsulinism in infancy and erectile dysfunction) are associated with dysfunctional K(+) channels due to mutations in genes encoding channel proteins. The therapeutic potential of KCOs in peripheral K(+) channelopathies is discussed. The identification of K(+) channel subtype specific openers offers discrete modulation of cellular systems creating a realistic therapeutic advance in the treatment of K(+) channelopathies. PMID- 11772257 TI - Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease. AB - Cilomilast (Ariflo, SB-207499) is an orally-active, second generation phosphodiesterase (PDE) inhibitor that may be effective in the treatment of asthma and chronic obstructive pulmonary disease (COPD). It has high selectivity for the cyclic AMP-specific, or PDE4, isoenzyme that predominates in pro inflammatory and immune cells and is ten-fold more selective for PDE4D than for PDE4A, B and C. In vitro, cilomilast suppresses the activity of many pro inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD and is highly active in animal models of these diseases. Cilomilast demonstrates a markedly improved side effect profile over the archetypal PDE4 inhibitor, rolipram, which has been attributed to its inability to discriminate between the high affinity rolipram binding site and the catalytic domain of the enzyme, and the fact that it is negatively charged which at physiological pH should limit its penetration in to the CNS. In humans cilomilast is rapidly absorbed after oral administration, providing dose-proportional systemic exposure up to 4 mg, completely bioavailable, has a half-life of approximately 7 h and is subject to negligible first pass hepatic metabolism. Cilomilast is extensively metabolised with decyclopentylation, acyl glucuronidation and 3-hydroxylation of the cyclopentyl ring representing the principal routes. Most of the drug is excreted in the urine (approximately 90%) and faeces (6 - 7%) with unchanged cilomilast accounting for less than 1% of the administered dose. Cilomilast has been evaluated in Phase I, Phase II and Phase III trials and dose-response experiments have demonstrated a clinically significant increase in lung function and a perceived improvement in quality of life in patients with COPD. Trials of cilomilast in asthma have been less impressive although a trend towards improved lung function has been reported. Cilomilast is safe and well-tolerated at doses up to 15 mg in both short- and long-term dosing trials with a low incidence of adverse effects. No evidence for drug-drug interactions with commonly prescribed medications for COPD and asthma such as digoxin, corticosteroids, salbutamol, theophylline or warfarin has been found. Moreover, the pharmacokinetics of cilomilast are essentially the same in smokers and non-smokers, indicating that no dose adjustments of cilomilast will be required in patients with COPD. Thus, cilomilast displays a promising clinical profile in the treatment of inflammatory airway diseases, in particular COPD and the results of further Phase III trials are awaited with interest. PMID- 11772258 TI - Tresperimus: a new agent for transplant tolerance induction. AB - Tresperimus is a novel agent that induces allogeneic transplant tolerance. It is structurally related to deoxyspergualin (DSG) but has been modified to resist rapid hydrolysis in aqueous solution, which simplifies administration. Despite this modification, tresperimus's actions in experimental models seem almost identical to DSG. Initially, DSG was developed as an antitumour agent. Its antitumour efficacy appears limited but DSG and tresperimus have favourable effects on transplant rejection. A short course of tresperimus has been shown to have similar or greater quantitative effects to cyclosporin in bone marrow, cardiac and skin transplant models. However, qualitatively the effects are different. Prevention of rejection is due to induction of donor-specific tolerance without affecting immunity to third party antigens. In addition, CD4+ T cells from tresperimus-treated animals can transfer donor specific tolerance to naive animals, an effect not seen with cyclosporin or other traditional immunosuppressive drugs. The mechanism by which tolerance is induced is not clear. Tresperimus (like DSG) binds to Hsc70, which among other effects inhibits nuclear localisation of NF-kappa B. NF-kappa B nuclear localisation is induced by CD40 ligation in antigen-presenting cells, an important early step in T-cell co stimulation. NF-kappa B is also required for CD28 ligation signalling, important in late co-stimulation. It also is involved in B-cell activation, via CD40 ligation and kappa light chain production. Hsc70 is also required for efficient cytosolic peptide chaperoning to MHC class I molecules. Presumably, it is disruption of T-cell/dendritic cell interaction that leads to induction of T-cell anergy. Tresperimus is well-tolerated. The main dose limiting side effects are orthostatic hypotension and peri-oral numbness. These effects are dependant on blood drug levels and, due to its short half-life, correspond to the rate of infusion. Phase II/III clinical studies are accruing patients and results have not yet been reported. Tresperimus shows promise in the move from immunosuppression to tolerance induction as the way to prevent transplant rejection and graft versus host disease (G v HD). However, its role in tolerance induction and effect in combination with other tolerance inducing agents e.g., CTLA-4-Ig and anti-CD40L antibodies remains unclear. PMID- 11772259 TI - Efflux in bacteria: what do we really know about it? AB - Efflux is the process in which bacteria transport compounds outside the cell which are potentially toxic, such as drugs or chemicals or compounds. Efflux pumps can be identified not only by biochemical, microbiological, or molecular means but with the availability of microbial genomic sequences, by the application of bioinformatics analysis of DNA sequences for key conserved structure motifs. Efflux has been identified as a relevant contributor to bacterial resistance in the clinic and is now recognised as one of the most important causes of intrinsic antibiotic resistance in bacteria, especially in Pseudomonas aeruginosa. With the recognition of efflux as a major factor in bacterial resistance, several companies have invested in the identification and development of bacterial efflux pump inhibitors. Among those, Microcide, Pfizer, Paratek and several academic laboratories are in the process of exploring efflux pump inhibitors from synthetic, natural products and peptidomimetics. Inhibiting bacterial efflux with a non-antibiotic inhibitor would restore activity of an antibiotic subject to efflux (similar to the use of beta-lactamase inhibitors to combat beta-lactamase production by bacteria). The feasibility of such an approach has been experimentally demonstrated in vitro and in vivo for efflux reversal of levofloxacin. PMID- 11772260 TI - Non-nucleoside reverse transcriptase inhibitors: perspectives on novel therapeutic compounds and strategies for the treatment of HIV infection. AB - At present, the nucleoside reverse transcriptase (RT) inhibitors and protease inhibitors (PI) have dominated the therapeutic options for the treatment of human immunodeficiency virus (HIV) infection. From the initial monotherapeutic strategies, to the widely accepted multi-drug cocktails of today, the use of these two classes of compounds has successfully prolonged patient survival following infection with HIV. The efficacy of the multi-drug cocktails has delayed the onset of disease and generated hope that long-term therapy might allow the natural immune response to HIV infection to control both virus replication and pathogenesis within the context of an intact immune system despite the continuing presence of virus in various reservoirs within the body and the inability of these therapies to completely eradicate virus. However, the use of antiretroviral compounds for prolonged periods of time has also resulted in the appearance of significant drug-induced toxicity and metabolic abnormalities, as well as drug-induced variations in disease progression. Thus, continued research and development to identify new and improved antiretroviral agents will be a critical requirement in the foreseeable future. This ongoing research and development should also consider the challenges of defining more effective use of existing therapeutic agents, including the non-nucleoside reverse transcriptase inhibitors (NNRTIs). PMID- 11772261 TI - Strategies for treating HIV-related lipodystrophy. AB - HIV-related lipodystrophy has emerged as one of the most prevalent problems for patients with HIV, since this infection can now be seen as a chronic disease. Despite its growing importance, crucial issues such as aetiopathogenesis, diagnosis, prevention and therapy remain largely unknown and unexplored. Current evidence suggests that aetiology is multifactorial. HIV infection, antiretroviral therapy and patient-related factors probably all contribute to the development of lipodystrophy. The lack of a formal definition and the nature of wasting syndromes that affect HIV-infected patients can hinder the diagnosis and treatment of lipodystrophy. Body fat changes have a major negative impact on the quality of life of patients. Metabolic abnormalities are also well known cardiovascular risk factors that can increase the morbidity and mortality due to cardiovascular disorders in a relatively young population. As yet, we do not know whether lipodystrophy is preventable or reversible. Several therapeutic approaches have been tested with limited success, however potential complications must be considered. These therapeutic approaches include general health measures (diet, exercise and discontinuation of smoking), switching antiretrovirals (from protease inhibitors to non-nucleoside reverse transcriptase inhibitors or abacavir, or from stavudine to other nucleoside reverse transcriptase inhibitors) and use of drugs with metabolic effects (metformin, thiazolidinediones, recombinant growth hormone and anabolic steroids). A judicious use of available data, and opting for an individualised approach seems the best option for management of this problem at present. PMID- 11772262 TI - Experimental and emerging therapies for chronic hepatitis C virus infection. AB - Hepatitis C virus infection is prevalent throughout the world and is associated with substantial morbidity, mortality and health economic burden. No effective preventative measure, including vaccination, is currently available. Incremental and substantial progress in the rate of viral eradication using interferon-based therapies has been made over the past decade. The most recent advance has been related to the development of a pegylated form of IFN-alpha by two independent pharmaceutical companies. Pegylation of IFN-alpha appears to prolong its half life, allowing for less frequent dosing. Reports have suggested that pegylated interferons are also associated with better efficacy for viral eradication in patients with hepatitis C virus. Slower progress also has been made in developing non-interferon-based therapeutic agents against hepatitis C virus, including protease inhibitors, helicase inhibitors, ribozymes, antisense therapies, cytokine-based therapies and T-cell-based therapeutic vaccines. PMID- 11772263 TI - Experimental and emerging therapies for sepsis and septic shock. AB - The underlying principles of sepsis therapy have remained unchanged for decades. These include: prompt institution of antimicrobial agents aimed at the inciting pathogen, source control directed at removal of the infection nidus whenever possible, and support of organ dysfunction. Despite advances in antibiotics, surgical techniques and organ support technology, the morbidity and mortality from sepsis-related diseases have remained substantially unchanged (30 - 50%). Immunomodulation of the inflammatory cascade has been suggested as a crucial but inadequately addressed element in the treatment of sepsis. The list of potential therapeutic targets has been growing as more and more mediators are identified in the pathogenesis of sepsis. To date, numerous anti-inflammatory agents, found to have favourable effects in animal models of septic shock, have been tested in a number of clinical trials on thousands of patients. In this first of a three part series, we go through some of the background and current strategies in sepsis therapy. In this review, we include the two novel therapies that have shown clear survival benefit in large, randomised, placebo-controlled, multi-centre trials, low-dose steroids and recombinant activated protein C. Also included in this review are studies on antithrombin III, platelet-activating factor antagonists, complement modulators, nitric oxide synthase inhibitors and caspase inhibitors (apoptosis inhibitors). PMID- 11772264 TI - New therapies and vaccines for meningococcal disease. AB - Meningococcal disease (MCD) is an important cause of morbidity and mortality. The pathophysiology consists of a complex interaction of bacterial and host factors, triggered by the release of endotoxin which initiates the inflammatory cascade, resulting in multi-organ failure, coagulopathy, capillary leak, metabolic derangement and eventually death. Prompt recognition and aggressive management are essential in reducing mortality. Over the past decade, there has been intense research into novel therapies and vaccines, with largely disappointing results. Therapies have been broadly divided into anti-endotoxin and anti-TNF-alpha therapies, treatment aimed at correcting coagulopathy and at blood purification and anti-inflammatory cytokine therapy. The reasons for the disappointing results in the search for new therapeutic strategies are difficult to identify. The disordered physiology in MCD results from a complex interaction of several mediators; therefore attempts to correct this by altering just one step represents a gross oversimplification of the process. In addition, the experimental model of endotoxaemia, which is often used, is a poor representation of an acutely ill patient with rapidly progressive shock. There have been several small or poorly designed trials, which have failed to reach definite conclusions. In order to yield conclusive results any future trials must be multicentre, randomised, controlled trials, but these are expensive and, in practice, difficult to conduct. The BPI trial (vide infra) was a significant step forward in this regard and demonstrated the ability to organise a large multicentred trial which can act as a template for future trials. Although the results were not significant there was an overall trend towards improved outcome in the treatment arm. Whilst the development of effective therapies and vaccines are awaited, the priorities at present must be the prompt recognition and aggressive management of disease. PMID- 11772265 TI - New developments in chemotherapy for non-invasive fungal infections. AB - Dermatomycosis and subcutaneous mycosis comprise the non-invasive fungal infections commonly encountered in clinical practice around the world. The limited activity of early topical antifungal agents prompted the development of more effective systemic agents. While griseofulvin has been used for more than four decades, the use of early azoles, such as ketoconazole have resulted in better patient compliance and thus greater success. However, poor response and recurrence in dermatomycosis, as well as toxicity associated with ketoconazole therapy, has led to the search for newer antifungal agents and more effective treatment strategies. Terbinafine, itraconazole and fluconazole have the advantage of non-toxicity and a broad spectrum of activity. An overview of non invasive fungal infections, antifungal agents in clinical use and recent developments in antifungal therapy is reviewed in this article. PMID- 11772266 TI - Diagnostic advantages and therapeutic options for giardiasis. PMID- 11772267 TI - Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias. AB - TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) is a member of the TNF superfamily of death ligands that selectively induces apoptosis in tumour cells of diverse origins. In this report, we have reviewed recent studies examining TRAIL/Apo2L-induced apoptosis in multiple myeloma (MM), a B-cell malignancy which, in spite of its initial sensitivity to steroids, cytotoxic and high-dose chemotherapy, remains incurable. Recently, we demonstrated that TRAIL/Apo2L induces apoptosis of steroid- and chemotherapy-sensitive and resistant MM cell lines. Moreover, TRAIL/Apo2L selectively induced apoptosis of patient MM tumour cells while sparing non-malignant bone marrow and peripheral blood mononuclear cells. In addition, TRAIL/Apo2L inhibited the growth of human plasmacytomas xenografted into mice. Importantly, TRAIL/Apo2L-induced apoptosis was unaffected by IL-6, a potent growth and survival factor for MM cells which, as we and others have previously shown, blocks various pro-apoptotic signals including Fas ligand, which like TRAIL/Apo2L is also a member of the TNF family of ligands. In view of the potential clinical application of TRAIL/Apo2L to the treatment of MM, we have attempted to discern intracellular mechanisms of action and resistance for TRAIL/Apo2L in MM, along with strategies to increase sensitivity and overcome resistance of MM cells to TRAIL/Apo2L. These studies demonstrated that doxorubicin, an agent which is commonly used to treat MM patients, upregulated the expression of the DR5 death-signalling TRAIL receptor and synergistically enhanced the pro-apoptotic effect of TRAIL on MM cells. Moreover, NF-kappaB inhibitors such as SN50 (a cell permeable inhibitor of NF kappaB nuclear translocation) as well as the proteasome inhibitor PS-341, which is currently in Phase II clinical trials, also enhanced the pro-apoptotic activity of TRAIL/Apo2L in MM cells. Lastly, TRAIL/Apo2L-induced apoptosis in MM cells was dependent on caspase-8 activation and inhibited by the caspase regulatory proteins FLIP and cIAP2. These studies provide a framework for the use of TRAIL/Apo2L as a single agent or as part of combination therapy for the treatment of MM. PMID- 11772268 TI - Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects. AB - Botulinum toxin (BTX) injections are a well-recognised therapeutic modality for the treatment of regional involuntary muscle disorders and recently BTX has been used for treatment of pain and inflammatory disorders. The primary purpose of this review is to discuss the mechanism of action of therapeutic BTX in light of both the traditional understanding of BTX pharmacological effects as well as new observations. The review will deal with clinical observations and relevant animal experimentation. The data and hypotheses presented are not only relevant to botulinum toxin technology but will certainly prove important in the basic mechanisms of some of the diseases where botulinum toxin has been successfully applied. BTX used clinically comprises botulinum neurotoxin (BoNT) complexed with non-toxic proteins. The non-toxic components of the BTX complexes stabilise the labile BoNT during purification and formulation as a therapeutic. The complex proteins may also have unrecognised clinical significance such as slowing diffusion in tissues or imparting stability. The mechanisms of BTX formulations acting on SNARE proteins are briefly reviewed providing a basis for BTX clinical applications. The potential for design of improved botulinum toxins and formulations is addressed. PMID- 11772270 TI - A novel therapeutic approach for Helicobacter pylori infection: the bismuth-based triple therapy monocapsule. AB - Helicobacter pylori infection causes peptic ulcer disease and must be regarded as a serious infectious disease. Over the past two decades treatment of the infection has been a controversial issue. Treatment is purely empirical and based on combinations of two, three or four existing drugs. Antimicrobial resistance is important and an observed increase in the prevalence of resistance may change the relative importance of certain antibiotics. Bismuth-based triple therapy with bismuth, tetracycline and metronidazole is a well investigated, cheap and FDA approved regimen to cure the infection. Adding a proton pump inhibitor (PPI) increases efficacy. A novel monocapsule ("Helicide") that contains bismuth, tetracycline and metronidazole simplifies the regimen. This new and patient friendly drug has been investigated in clinical studies and is expected to be released in North America in 2002. PMID- 11772269 TI - Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections. AB - Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-beta-D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad spectrum antifungal activity against Candida and Aspergillus spp. without cross resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida spp. and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the cytochrome P450 (CYP) enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients. PMID- 11772271 TI - Leptin: brains and bones. AB - Leptin, is a 16 kDa protein derived mainly, though not entirely, from white fat cells. It regulates the size of the body's fat load (i.e., energy reserves) and has a growing list of other functions. The latest addition is bone growth. The evidence so far indicates that leptin controls bone growth in two ways. It stimulates the release of an undefined hypothalamic osteoblast-inhibiting factor(s), which limits the amount of bone matrix that osteoblasts can make. Interestingly, it is itself a bone anabolic factor that directly stimulates bone growth by inducing osteoblasts to make IGF-I (insulin-like growth factor-I) and inhibiting osteoclast generation. PMID- 11772272 TI - Advances in the treatment of precocious puberty. PMID- 11772273 TI - Advances in the treatment of polycystic ovary syndrome. AB - Current treatment of polycystic ovary syndrome (PCOS) in women is essentially symptomatic. However, there is growing evidence that this disorder is an evolving condition and that it may be associated with major medical outcomes later in life. As a consequence, effective treatments should be instituted as soon as PCOS is diagnosed. Insulin resistance with associated hyperinsulinaemia and increased luteinising hormone (LH)-dependent androgen secretion from the ovary seem to play a central role in the pathogenesis of PCOS. Accordingly, the effects of attenuation of hyper-insulinaemia, LH excess or hyperandrogenism were recently assessed, with promising results. A consistent finding was that attenuation of insulin resistance and hyperinsulinaemia may correct the entire spectrum of endocrine, metabolic and reproductive abnormalities of PCOS in many subjects. PMID- 11772274 TI - Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus. AB - Amylin is a peptide hormone which is co-secreted with insulin from the pancreatic beta-cell. Type 1 diabetic individuals and some Type 2 diabetic individuals are characterised by amylin deficiency. Animal experiments have revealed several actions of amylin on intermediary metabolism, of these some have been demonstrated to be of potential physiological relevance in humans. In particular amylin appears to have important actions in controlling prandial glucose homeostasis. The peptide hormone inhibits postprandial glucagon secretion and delays gastric emptying thereby modifying postprandial hyperglycaemia in diabetic individuals which presumably adds to overall glycaemic control without a concomitant increase in the number of severe hypoglycaemic episodes. Moreover, amylin acts as a satiety agent. Amylin replacement may therefore improve glycaemic control in diabetes mellitus. However, human amylin exhibits physicochemical properties predisposing the peptide hormone to aggregate and form amyloid fibres, which makes it unsuitable for pharmacological use. A stable analogue, pramlintide, with actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide has therefore been developed. The efficacy and safety of pramlintide administration to diabetic individuals have been tested in a large number of clinical trials. It is the aim of this review to describe possible (patho)physiological actions of amylin as demonstrated in animal and human models, to discuss the background for potential amylin (analogue) replacement in diabetes mellitus and to review results from clinical trials with the amylin receptor analogue pramlintide. PMID- 11772275 TI - Therapeutic potential of PKC inhibitors in painful diabetic neuropathy. AB - Diabetic neuropathy accompanied by anomalies in pain perception is one of the most frequent complications in insulin-dependent diabetes in humans. Many clinical and experimental studies have suggested that diabetes or hyperglycaemia alters pain sensitivity. In humans, diabetic neuropathy can be associated with burning, tactile hypersensitivity. Behavioural reactions of hyperalgesia in animal models of diabetes have been described. However, the aetiology of these disturbances is still unknown, although metabolic factors such as hyperglycaemia or neurotransmitter alteration may be involved. Activation of protein kinase C (PKC) has been implicated in changes in pain perception. Phorbol esters, which activate PKC, enhance the thermal hyperalgesia in diabetic mice and enhance nociceptive responses after tissue injury induced by formalin. Electrophysiological experiments have shown that activation of PKC leads to long lasting enhancement of excitatory amino acid-mediated currents in dorsal horn neurones and trigeminal neurones. Thus, activation of PKC may underlie the neuronal sensitisation that produces hyperalgesia in diabetic neuropathy. PMID- 11772276 TI - Therapeutic potential of anti-oxidants and diabetic retinopathy. AB - Retinopathy, a severely disabling complication of diabetes mellitus, is today the leading cause of acquired blindness among young adults in developed countries. Good glycaemic control can attenuate the development of diabetic retinopathy but such metabolic control is often difficult to achieve and maintain and additional therapies need to be identified by which retinopathy can be prevented or arrested. Hyperglycaemia plays a critical role in the development and progression of retinopathy, but the mechanism by which hyperglycaemia results in the development of retinopathy is not clear. Oxidative stress is increased in the retina in diabetes. The possible sources of increased oxidative stress might include increased generation of free radicals or impaired anti-oxidant defence system. Dietary supplementation with anti-oxidants in animal models of diabetic retinopathy inhibits retinal metabolic abnormalities and retinal histopathology, suggesting that oxidative stress is associated with the development of retinopathy. The mechanism by which anti-oxidants inhibit retinopathy in diabetes warrants further investigation, but animal studies show that increasing the diversity of anti-oxidants provides significantly more protection than using any single anti-oxidant. Thus, supplementation with anti-oxidants represents an achievable adjunct therapy to help preserve vision in diabetic patients. PMID- 11772278 TI - Therapeutic potential of angiotensin II receptor antagonists. AB - The circulating renin-angiotensin system plays an important role in cardiovascular homeostasis. More importantly, the local tissue renin angiotensin plays a pivotal role in cell growth and remodelling of cardiomyocytes and on the peripheral arterial vasculature. In addition, the renin angiotensin system is related to apoptosis, control of baroreflex and autonomic responses, vascular remodelling and regulation of coagulation, inflammation and oxidation. The cardioprotective and vascular protective effects of the angiotensin receptive blockade appears to be related to selective blockade of the angiotensin II (A-II) Type I (AT(1)) receptors. However, there is now growing evidence showing that some of the effects of AT-II receptor blockers (ARBs) are related to the activation of the kinin pathways. This paper will review some of the recent mechanisms related to the cardiovascular effects of angiotensin and more specifically of ARBs. This paper will present the novel data on the role of ARB in the development of atherosclerosis, vascular remodelling, coagulation balance and autonomic regulation. Finally, the role of ARBs, used alone or in combination with ACE inhibitor in patients with heart failure, will be discussed. PMID- 11772277 TI - Therapeutic potential of bone morphogenetic proteins. AB - Recently, there has been substantial progress in the area of bone morphogenetic protein (BMP) research. This review serves as an up-to-date summary of the history of BMPs, the mechanisms of BMP signalling and the role of BMPs in adipose, kidney, liver, bone and nervous system. The potential of BMPs as therapeutic agents will also be discussed. PMID- 11772279 TI - Development of distamycin-related DNA binding anticancer drugs. AB - The relatively low therapeutic index of the clinically used alkylating agents is probably related to the fact that these compounds cause DNA damage in a relatively unspecific manner, mainly involving guanine-cytosine rich stretches of DNA present in virtually all genes, therefore inducing unselective growth inhibition and death, both in neoplastic and in highly proliferative normal tissues. These considerations explain why in the last twenty years there has been an increasing interest in the identification of compounds which can target DNA with a much higher degree of sequence specificity than that of conventional alkylators. Minor groove binders (MGBs) are one of the most widely studied class of alkylating agents characterised by a high level of sequence specificity. The prototype of this class of drugs is distamycin A which is an antiviral compound able to interact, non-covalently, in theminor groove of DNA in A-T rich regions. It is not cytotoxic against tumour cells and thus has been used as a carrier for targeting cytotoxic alkylating moieties in theminor groove of DNA. The benzoyl mustard derivative of distamycin A, tallimustine, was found to be able to alkylate the N(3) of adenine in theminor groove of DNA only in the target hexamer 5'-TTTTGA or 5'-TTTTAA. Tallimustine was investigated in the clinic and was not successful because it causes severe bone marrow toxicity. The screening of other distamycin derivatives, which maintain antitumour activity and exhibit much lower toxicity against human bone marrow cells than tallimustine led to the identification of brostallicin (PNU-166196) which is currently under early clinical investigation. Although MGBs which bind DNA in A-T rich regions have not fulfilled the expectations, it is too early to draw definitive conclusions on this class of compounds. The peculiar bone-marrow toxicity observed in the clinic both with tallimustine or with CC-1065 derivatives is not necessarily a feature of all MGBs, as indicated by recent evidence obtained with brostallicin and other structurally unrelated MGBs (e.g., ET-743). PMID- 11772280 TI - Recent advances in the treatment of epithelial ovarian cancer. AB - Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with the overall 5-year survival being just 30%. The majority of patients with this disease will require treatment with cytotoxic chemotherapy. It is now well established that the platinum agents (cisplatin or carboplatin) are the most important drugs to be included in first-line regimens. More recently, randomised trials have confirmed the benefit of the addition of taxanes to platinum containing regimens and the standard of care has become the combination of carboplatin and paclitaxel. Several unanswered questions remain regarding the optimal schedule, the optimum duration of treatment, possible benefits to be gained from the addition of other drugs and whether paclitaxel the best taxane. Despite high response rates to first line chemotherapy, the majority of patients with advanced ovarian cancer will relapse and will be candidates for further chemotherapy, which can palliate symptoms and improve survival even in recurrent disease. For a patient relapsing within six months of first-line treatment, studies have shown that there is little point in rechallenge with the same drugs. However, for patients who have a longer treatment-free interval the response rates to rechallenge with platinum is significant. A number of drugs have been shown to have activity in platinum- and taxane-refractory disease and are approved for this and/or other applications. These include topotecan, etoposide, pegylated liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxaliplatin and vinorelbine. Anti-oestrogens such as tamoxifen have a small but significant response rate. Recurrent ovarian cancer is a good setting to test investigational agents and compounds with promising activity including new platinums and taxoids, as well as a range of new compounds. Non-cytotoxic approaches that are showing promise include therapies designed to overcome drug resistance, signal transduction inhibitors, immunotherapy and gene therapy. PMID- 11772281 TI - The place of pegvisomant in the management of acromegaly. AB - Conventional treatments for acromegaly include surgery, radiotherapy, dopamine agonists and somatostatin (SMS) analogues, which effect disease control by lowering circulating growth hormone (GH). Due to variability in tumour characteristics, combinations of these treatment modalities leave a significant number of patients with sub-optimal serum GH and insulin-like growth factor-I (IGF-I) levels, which have been linked to increased morbidity and mortality. The GH receptor antagonist pegvisomant is a genetically engineered analogue of GH that prevents functional dimerisation of the growth hormone receptor (GHR); a process that is critical to GH action at the cellular level. A crucial amino acid substitution at Gly(120) to Arg(120) within the third alpha helix of the antagonist prevents functional GHR dimerisation. Pegvisomant represents a novel treatment for acromegaly as, unlike existing treatment modalities, the effectiveness of pegvisomant is independent of pituitary tumour characteristics. Initial clinical studies in patients with active acromegaly have demonstrated serum IGF-I normalisation in over 90% of patients receiving 20 mg per day, such that, in terms of serum IGF-I normalisation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvisomant and questions regarding pituitary tumour growth and altered liver function remain, this therapy offers the prospect of serum IGF I normalisation in the vast majority of patients with active acromegaly. PMID- 11772282 TI - Trimegestone: expanding therapeutic choices for the treatment of the menopause. AB - Trimegestone is a novel norpregnane progestin, which has a potent progesterone receptor and very low androgen receptor affinities but no detectable affinity to oestrogen receptor. Trimegestone has been developed for use in conjunction with oestrogen for postmenopausal hormone replacement therapy (HRT). The dose of trimegestone required for endometrial safety was optimised in a dose ranging study. Oral trimegestone was administered at 0.05, 0.1, 0.25 and 0.5 mg/day, days 15 - 28 along with continuous oral micronised oestradiol at 2 mg daily. The majority of women in the four dose groups experienced relief of climacteric symptoms by the end of the third treatment cycle. The incidence of pre-menstrual tension-like symptoms was low and did not differ between the four dose groups. After 6 months of treatment, the bleeding pattern showed a clear dose-dependent modulation such that the higher the dose of trimegestone administered the more predictable was the day of onset of bleeding and the shorter and lighter the bleeding episodes became. This was further confirmed in another study comparing trimegestone in 0.5 and 0.25 mg doses to norethisterone acetate, where women on the 0.5 mg dose experienced more favourable bleeding pattern compared with the lower dose of 0.25 mg or to norethisterone acetate. In the dose ranging study, 96% of endometrial specimens obtained at the end of the study had secretory changes. The lipoprotein profile measured at baseline, 3 and 6 months during the dose ranging study confirmed the fact that trimegestone, irrespective of the dose, did not negate the beneficial effects of oestrogen on lipids. CONCLUSION: trimegestone is an effective and well-tolerated new progestin, which does not negate the beneficial effects of oestrogen on lipids. PMID- 11772283 TI - Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts. AB - Immunocompromised hosts are at increased risk of cytomegalovirus (CMV) infection and serious CMV disease. CMV infection is an important cause of morbidity among patients infected with HIV and after solid organ transplantation (SOT) and may cause life-threatening disease in allogeneic stem cell transplant (SCT) recipients. The introduction into clinical use of potent antiviral compounds and of rapid detection assays for CMV during the past two decades has allowed development of strategies for the prevention and treatment of disease caused by CMV in these groups of immunocompromised patients. At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease. However, these agents have a poor oral bioavailability and, for systemic use, require iv. administration for most indications. Valganciclovir is an oral prodrug of ganciclovir, with a 10-fold greater bioavailability than oral ganciclovir. Studies of the pharmacokinetics of valganciclovir among HIV-infected CMV-seropositive patients and liver transplant recipients suggest that this oral compound has the potential to replace both oral and iv. ganciclovir in many situations if it is shown to be as efficacious and safe as those ganciclovir formulations in immunodeficient patients. In the first part of this review, currently established approaches to the management of CMV infection and disease in SCT and SOT recipients and HIV-infected patients are discussed to highlight possible indications for future valganciclovir use; in the second part, data from human studies of valganciclovir are presented. PMID- 11772284 TI - Statins in the 21st century: end of the simple story? AB - The development of the HMG-CoA reductase inhibitors (the statins) has lead to important advances in the management of cardiovascular disease. There have several landmark mortality and morbidity clinical trials with the statins. The 4S (Scandinavian Simvastatin Survival Study) was the first large-scale randomised cholesterol-lowering trial to show a decrease in mortality. In patients with coronary heart disease and relatively high cholesterol, simvastatin decreased mortality, hospital stays, the risk of undergoing myocardial re-vascularisation, stroke and transient ischaemic attack. The CARE (Cholesterol and Recurrent Events) trial showed that lowering average cholesterol levels after myocardial infarction with pravastatin reduced a composite primary end point of coronary mortality and myocardial infarction, coronary bypass surgery, angioplasty and strokes. The LIPID (Long-term Intervention with Pravastatin in Ischaaemic Disease) study showed that lowering average cholesterol levels after previous myocardial infarction or unstable angina reduced mortality. WOSCOPS (The West of Scotland Coronary Prevention Study) was the first trial to demonstrate the benefit of pravastatin, as primary prevention for cardiovascular disease, in men with high cholesterol levels. AFCAPS/Tex CAPS (The Air Force/Texas Coronary Atherosclerosis Prevention Study) showed that the benefits of lowering cholesterol levels were also evident in healthy men and women who initially had average cholesterol levels. Rather surprisingly the reductions in mortality and morbidity with statins are only associated with small improvements in coronary angiographic findings. A preliminary study indicated than lovastatin prevented restenosis, but larger and better-controlled studies indicate that the statins do not have beneficial effects in restenosis. Effects other than lipid-lowering or as a consequence of their lipid-lowering may contribute to the beneficial effects of statins. These effects include improvement in vascular endothelial function, cardiac remodelling, changes in blood rheology, anti-oxidant, anti-inflammatory and anti-hypertensive actions. PMID- 11772285 TI - Antiglucocorticoid drugs in the treatment of depression. AB - A confluence of evidence indicates that prolonged elevation in gluco-corticoid level may result in disturbances of mood and cognition. In Cushing's syndrome, hypersecretion of cortisol is associated with a high incidence of depression, impairment in memory and hippocampal atrophy. Pharmacological usage of glucocorticoids is similarly productive of mood change and memory deficit. In patients with endogenous depression, hypercortisolaemia is associated with cognitive dysfunction and possibly a decrease in hippocampal volume. In each of these conditions, reduction of glucocorticoid level, either through discontinuation of steroid treatment or through usage of agents that block glucocorticoid synthesis, ameliorates the adverse behavioural effects. Traditional antidepressant agents may, in addition, stabilise mood through actions on the hypothalamic-pituitary adrenocortical (HPA) system. Although clinical usage of the currently available antiglucocorticoid drugs is limited by significant adverse side effect profiles, development of drugs specifically targeting the glucocorticoid receptor may lead to innovative strategies in the treatment of mood disorders. PMID- 11772286 TI - New developments in psychopharmacology of attention deficit hyperactivity disorder. AB - Stimulants have been the mainstay of the psychopharmacological treatment of attention deficit hyperactivity disorder (ADHD) for over 60 years. In the last 5 years, there have been a number of important developments in terms of potential new treatments for ADHD. Since stimulants have such a short half-life, considerable research has focused on the development of new delivery systems that will allow once-a-day dosing. New formulations of both amphetamine (AMP) and methylphenidate (MPH) have appeared which differ in terms of their optical isomers from the commonly used compounds. A wide variety of compounds are currently in development as therapeutic agents for ADHD. Some, like the stimulants, primarily impact the noradrenergic and dopaminergic neurotransmitter systems, while others have novel effects on the cholinergic, histaminergic and peptidergic systems. Advances in the pharmacogenetics of ADHD may lead to the development of yet more compounds in the near future. PMID- 11772287 TI - Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy. AB - The blood-brain barrier (BBB) to water-soluble drugs and macromolecules can be opened in vivo by infusing a hypertonic solution of arabinose or mannitol into the carotid artery for 30 sec. Opening involves widening of tight junctions between endothelial cells of the cerebrovasculature and is mediated by endothelial cell shrinkage, vascular dilatation associated with removal of water from brain, and modulation of the contractile state of the endothelial cytoskeleton and junctional proteins by increased intracellular calcium. A 10 fold increase in BBB permeability to intravascular substances, lasting about 10 min following osmotic exposure, reflects both increased diffusion and bulk fluid flow from blood into brain. Furthermore, recent evidence indicates that the duration of peak BBB opening can be extended beyond 30 min, by pre-treatment with a Na(+)/Ca(2+) channel blocker. In experimental animals, the osmotic method has been used to grant wide access to brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, viral vectors for gene therapy and enzymes. Ongoing multi-centre clinical studies suggest that the method, when used with intra-arterially administered anticancer drugs, can prolong survival in patients with malignant brain tumours, with minimal morbidity. However, controlled clinical trials are critical to see if the osmotic procedure with intra-arterial drugs enhances survival in brain tumour patients compared with intra-arterial drug alone. PMID- 11772288 TI - The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control. AB - Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain. PMID- 11772290 TI - Statins and neuroprotection. AB - The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia. PMID- 11772289 TI - Advances in pharmacological treatment of migraine. AB - Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation. PMID- 11772291 TI - Neuroprotection for Parkinson's disease: a new approach for a new millennium. AB - Parkinson's disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. However, the medium to long-term efficacy of this pharmacotherapy, mainly consisting of dopaminomimetics like L -dopa and dopamine receptor agonists, suffers greatly from the unrelenting progression of the disease process underlying PD, i.e., the degeneration of neuromelanin-containing, dopaminergic neurones in the substantia nigra. Efforts concentrated on understanding the mechanisms of dopaminergic cell death in Parkinson's disease have led to identification of a large variety of pathogenetic factors, including excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, production of inflammatory mediators, loss of trophic support, and apoptosis. Therapeutic approaches aimed at correcting these abnormalities are currently being evaluated on their efficacy as neuroprotectants for PD. Here, we focus on the process of dopamine auto oxidation, the chain of reactions leading to the formation of neuromelanin, as an often overlooked, yet obvious pathogenetic factor. In particular, we discuss the option of drug-mediated stimulation of endogenous mechanisms responsible for the detoxification of dopamine auto-oxidation products as a novel means of neuroprotection in Parkinson's disease. PMID- 11772292 TI - Eletriptan. AB - Eletriptan (Relpax, Pfizer) is one of a group of anti-migraine medications commonly referred to as 'triptans'. It is a potent serotonin agonist at the 5 HT(1B/1D) receptor and is indicated for the acute treatment of migraine headaches. Eletriptan is administered orally. It is rapidly absorbed and has a bioavailability of 50% compared to 14% for sumatriptan. The relatively high lipophilicity of eletriptan compared to sumatriptan may explain its faster oral absorption and shorter time to onset of action. Results from comparative studies between oral eletriptan and sumatriptan indicate that eletriptan 80 mg was superior to sumatriptan 100 mg in onset of action, headache response rate, pain free response rate and relief of associated migraine symptoms at the 1 or 2 h time intervals. Although there was a modest increase in adverse events with eletriptan 80 mg than with sumatriptan 100 mg, eletriptan received a high patient acceptability rating (84%). PMID- 11772293 TI - Exisulind, a selective apoptotic antineoplastic drug. AB - Exisulind (Aptosyn, Cell Pathways, Inc.) is the first of a new class of targeted, pro-apoptotic drugs that show promise in the treatment of cancer. These agents induce apoptosis (i.e., programmed cell death) in a broad range of pre-cancerous and cancerous tissues without affecting normal cells. The antineoplastic effect of exisulind appears to be the result of activation of protein kinase G (PKG) which leads to multiple downstream effects culminating in apoptosis. Exisulind has demonstrated antineoplastic activity in solid tumour and haematological cancer cell lines and is an inhibitor of tumour growth in rodent models of colon, prostate, bladder, mammary and lung cancer. Preclinical data evaluating selective apoptotic antineoplastic drugs (SAANDs) in combination with various chemotherapy drugs indicates additive or synergistic antineoplastic effects. In clinical studies, exisulind prevented colorectal polyp formation in patients with familial adenomatous polyposis (FAP) over 24 months. In a randomised, placebo-controlled study of prostate cancer patients, exisulind inhibited the rise of prostate specific antigen (PSA) in men with PSA progression after radical prostatectomy. Exisulind has been well-tolerated by most patients in clinical trials. In conclusion, preclinical evidence and early clinical results suggest that exisulind and other drugs in this class may have wide applications in treating cancer both as monotherapy and in combination with chemotherapy and other targeted agents. PMID- 11772294 TI - Novel agents for managing dyslipidaemia. AB - An elevated low-density lipoprotein (LDL) cholesterol level is a strong predictor of coronary heart disease (CHD) risk. Over the past seven years, equally strong evidence has accumulated that lowering LDL cholesterol with HMG-CoA reductase inhibitors or statins reduces CHD risk and there is now widespread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholesterol reduction and whether, in people with very high levels, it would be preferable to achieve the LDL cholesterol goal with a powerful statin alone or combined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertriglyceridaemia. Already prevalent as a risk factor for CHD, this abnormality has been linked with insulin resistance, which is likely to increase greatly over the next decade, along with increasing obesity and diabetes. Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds. Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase. Future emphasis will be on correcting all lipid abnormalities for the prevention of CHD, not just lowering LDL cholesterol. PMID- 11772295 TI - Cardiac protection by pharmacological modulation of inflammation. AB - Inflammation is a reaction to primary injury of various kinds, such as infection and trauma, which has both beneficial and detrimental effects. Inflammation has been associated with major diseases of the heart and vessels. Research has focused not only on ischaemia but also on post-ischaemic reperfusion, which is known to activate and amplify the inflammatory response. Although reperfusion should always be attempted in the clinical environment, it has been shown experimentally that it can cause some cardiac damage, in addition to that caused by ischaemia. Therefore, it is reasonable to attempt to increase the benefit obtainable with reperfusion by modulating inflammatory processes triggered by reperfusion itself. In this field, different potential therapeutic targets have been identified and interventions have been tested over the last 30 years. With the exception of adenosine, which probably does not act merely through inhibition of the inflammatory response, no other compounds have yet proven successful in clinical trials. Active research is ongoing. Broadening the approach from the heart to the cardiovascular system, promising data is emerging on cardiovascular protection conferred by statins in patients with coronary heart disease (CHD) and high levels of C-reactive protein (CRP), a systemic marker of inflammation. Similarly, results of trials aimed at preventing cardiovascular events by eradicating chronic infections will be among the first to directly test whether such therapies will decrease risks of cardiovascular disease. PMID- 11772296 TI - Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders. AB - Tissue factor (TF) plays a crucial role in the pathogenesis of thrombotic, vascular and inflammatory disorders. Thus, the inhibition of this membrane protein provides a unique therapeutic approach for prophylaxis and/or treatment of various diseases. Tissue factor pathway inhibitor (TFPI), the only endogenous inhibitor of the TF/Factor VIIa (FVIIa) complex, has recently been characterised biochemically and pharmacologically. Studies in patients demonstrated that both TF and TFPI may be indicators for the course and the outcome of cardiovascular and other diseases. Based on experimental and clinical data, TFPI might become an important drug for several clinical indications. TFPI is expected to inhibit the development of post-injury intimal hyperplasia and thrombotic occlusion in atherosclerotic vessels as well as to be effective in acute coronary syndromes, such as unstable angina and myocardial infarction. Of special interest is the inhibition of TF-mediated processes in sepsis and disseminated intravascular coagulation (DIC), which are associated with the activation of various inflammatory pathways as well as of the coagulation system. A Phase II trial of the efficacy of TFPI in patients with severe sepsis showed a mortality reduction in TFPI- compared to placebo-treated patients and an improvement of organ dysfunctions. TFPI can be administered exogenously in high doses to suppress TF mediated effects, alternatively high amounts of TFPI can be released from intravascular stores by other drugs, such as heparin and low molecular weight heparins (LMWH). Using this method high concentrations of the inhibitor are provided at sites of tissue damage and ongoing thrombosis. At present, clinical studies with TFPI are rather limited so that the clinical potential of the drug cannot be assessed properly. However, TFPI and its variants are expected to undergo further development and to find indications in various clinical states. PMID- 11772297 TI - An update on the status of endothelin receptor antagonists for hypertension. AB - Endothelin receptor antagonists (ETRA) are actively developed by the pharmaceutical industry for several cardiovascular indications. In the context of hypertension, preclinical studies are increasingly focused on prevention or regression of end-organ damage and drug combination than on control of arterial pressure in monotherapy, as most experimental models have already been studied. In general, the antihypertensive effect of ETRA is limited but the overwhelming efficacy of this class of drugs to prevent several end-organ damages warrants judicious combination. However, the few studies looking at regression of hypertension-induced cardiovascular alterations proved less successful, suggesting that ETRA should be used early in the treatment of hypertension to obtain full benefit. Judging from the progression of ongoing trials and the development of new trials patients suffering from pulmonary hypertension and heart failure may be the first to benefit from this new class of drugs. However, it is expected that once on the market, responsive subsets of hypertensive patients will be identified and will benefit from end-organ protection. PMID- 11772298 TI - Inhaled nitric oxide in cardiology. AB - Inhaled nitric oxide (INO) allows selective pulmonary vasodilatation with rapidity of action. It is effective in the acute management of reversible pulmonary hypertension in cardiac medical and surgical patients and is also useful in assessing the pulmonary vasodilator capacity in patients with chronic pulmonary hypertension. This review will examine the role of INO in the management of cardiac patients, compared to alternatives where available. The use of INO in cardiac failure, post-operative cardiac patients, patients with congestive cardiac failure or congenital heart disease will also be reviewed. Newer alternatives with prolonged pulmonary activity and simpler administration are also discussed. PMID- 11772299 TI - Novel angiotensin II inhibitors in cardiovascular medicine. AB - Blockade of the renin-angiotensin-aldosterone cascade is now recognised as a very effective approach to treat hypertensive, heart failure and high cardiovascular risk patients and to retard the development of renal failure. The purpose of this review is to discuss the state of development of currently available drugs blocking the renin-angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II receptor antagonists, with a special emphasis on the results of the most recent trials conducted with AT(2) receptor antagonists in heart failure and Type 2 diabetes. In addition, the future perspectives of drugs with dual mechanisms of action, such as NEP/ACE inhibitors, also named vasopeptidase inhibitors, are presented. PMID- 11772300 TI - Therapeutic potential of GP IIb/IIIa receptor antagonists in acute myocardial infarction. AB - The management of acute myocardial infarction (AMI) has changed dramatically over the last two decades, with the addition of fibrinolytic agents and primary coronary intervention (PCI). The more recent development of the glycoprotein (GP) IIb/IIIa antagonists, a new class of potent antiplatelet drugs, has the potential to considerably enhance the treatment of AMI patients. A number of recent studies have highlighted the potential incremental benefits with adjunctive IIb/IIIa targeted therapy. In this review, we will discuss the pathophysiology of myocardial infarction (MI), the physiology and role of platelets in thrombosis and describe the currently available drugs. We will briefly summarise the results of recent clinical trials, discuss some key forthcoming trials and attempt to describe how GP IIb/IIIa antagonists may directly impact the immediate and near future day-to-day care of patients with AMI. PMID- 11772301 TI - Therapeutic potential of AGE inhibitors and breakers of AGE protein cross-links. AB - Glucose and other reducing sugars react non-enzymatically with proteins leading to the formation of advanced glycosylation end products (AGEs) and AGE-derived protein cross-linking. Formation of AGEs is a normal physiological process, which is accelerated under the hyperglycaemic condition in diabetes. Under normal conditions, AGEs build up slowly and accumulate as one ages. Numerous studies have indicated that AGEs contribute to the pathological events leading to diabetic complications, such as age-related diseases, including nephropathy, retinopathy, vasculopathy and neuropathy. Potential therapeutic approaches to prevent these complications include pharmacological inhibition of AGE formation and disruption of pre-formed AGE-protein cross-links. Studies using animal models and preliminary clinical trials have shown the ability of the AGE-inhibitor, pimagedine and the cross-link breaker, ALT-711, to reduce the severity of pathologies of advanced glycosylation. These agents offer potential treatments for glucose-derived complications of diabetes and ageing. PMID- 11772302 TI - Potential methods to prevent interstitial fibrosis in renal disease. AB - Almost all forms of end stage renal disease (ESRD) are characterised by progressive interstitial fibrosis and tubular atrophy. Since most forms of chronic renal failure are initiated by inflammatory processes, anti-inflammatory strategies can be successful, if initiated early, in preventing progression of the disease process. Unfortunately, in most cases the disease is only detected clinically following robust progression of interstitial fibrosis. In these patients, control of secondary risk factors, such as hypertension and hyperglycaemia, can slow the progression rate but cannot stop the process completely. Certainly, ACE inhibitors remain the mainstay of preserving renal function. However, additional therapies are needed for the effective treatment of progressive renal fibrosis. A number of compounds have shown some very potent antifibrotic properties in vitro and in vivo, and are currently undergoing further evaluation. This review discusses the most promising among them. However, few of the therapeutic agents discussed here have been tested clinically. Studies evaluating the potential of a number of these have just commenced whereas for many others clinical use is still many years away. However, some very promising reagents may enhance our clinical arsenal within a relatively short period of time. PMID- 11772303 TI - SLI381: a long-acting psychostimulant preparation for the treatment of attention deficit hyperactivity disorder. AB - SLI381 (Adderall-XR) is a longer-acting form of Adderall, a compound of mixed amphetamine salts that is now the most frequently prescribed brand of psychostimulant medication for attention-deficit hyperactivity disorder (ADHD) in the US. It has been demonstrated to be a safe and effective treatment for ADHD in school-age children. To date, the efficacy of SLI381 has been evaluated in controlled studies of over 500 patients. The therapeutic effects of SLI381 on the core symptoms of ADHD, as well as the duration of action of the formulation, have been demonstrated to persist for 12 h, with both greater efficacy and duration of effects seen at higher doses. Both behavioural and cognitive performance measures are improved throughout the school day and into post-school activities. The incidence of common stimulant-emergent side effects with SLI381 was no different than that seen with the existing Adderall preparation. Additionally, the frequency with which most stimulant-related side effects were experienced did not demonstrate a consistent dose-related incidence, with the exception of anorexia. SLI381 received a letter of approvability in August 2001 and will probably be approved in the immediate future by the US FDA. This formulation represents a valuable addition to the available pharmacotherapeutic options for ADHD by providing an amphetamine-based stimulant offering the advantages of once-daily dosing accompanied by the clinical benefits of ADHD symptom control associated with the now widely used Adderall preparation. PMID- 11772304 TI - Alteplase: descendancy in myocardial infarction, ascendancy in stroke. AB - Tissue type plasminogen activator is available, through recombinant technology, for thrombolytic use as alteplase. Alteplase is relatively clot specific and should cause less bleeding side effects than the non-specific agents such as streptokinase. Alteplase has been used successfully in evolving myocardial infarction (MI) to reopen occluded coronary arteries. It is probably equally effective or superior to streptokinase in opening arteries and reducing mortality in MI. Alteplase is most effective when given early in MI and is probably ineffective when given 12 h after the onset of symptoms. The effectiveness of alteplase in MI can be increased by front loading with a bolus of 15 mg, followed by an infusion of 50 mg over 30 min and 35 mg over 60 min. Percutaneous transluminal coronary angioplasty or stenting is associated with a greater patency and lower rates of serious bleeding, recurrent ischaemia and death than alteplase in MI and is likely to take over from alteplase as the standard MI treatment. A reduced dose of alteplase to increase coronary artery patency prior to angioplasty may be useful in MI. An exciting new indication for the use of alteplase is in stroke, where it has become the first beneficial intervention. Alteplase is used to reopen occluded cerebral vessels but is associated with an increased risk of intracerebral haemorrhage. Alteplase is beneficial if given within 3 h of the onset of stroke but not after this time period. Therefore, the next challenge is to increase the percentage of people being diagnosed and treated within this period. Clinical trials have not established a role for alteplase in the treatment of acute coronary syndromes or deep vein thrombosis. However, alteplase is useful in treating pulmonary thromboembolism and peripheral vascular disease. PMID- 11772305 TI - Ongoing clinical trials in systemic hypertension. AB - Hypertension was identified as a cardiovascular risk factor in the late fifties and still remains a public health issue. The number of patients treated reaches only half of those diagnosed and, of those treated, half fail to reach target blood pressure. Furthermore, the number of antihypertensive drugs reaching the market has increased exponentially in the last few years, however, the impact on treatment and on attaining target blood pressure levels remains to be seen. The high percentage of treated patients who do not reach target blood pressure, combined with the high number of patients requiring more than one antihypertensive drug, have triggered a series of long-term morbidity and mortality trials comparing different therapeutic approaches ('new' pharmacological classes vs. 'old' pharmacological classes). These are described in this paper. PMID- 11772306 TI - Novel pharmacological agents in clinical development for solid tumours. AB - For decades, cancer therapy has focused on DNA-directed mechanisms of cytotoxicity, utilising agents with limited efficacy and significant toxicity. Recent advances in tumour biology have elucidated the molecular pathways implicated in the pathogenesis and progression of cancers and have resulted in the discovery of a variety of novel molecular targets for therapeutic intervention. Promising novel agents targeting signal transduction pathways, cell cycle regulation, angiogenesis and apoptosis are in clinical testing and are discussed in this review. PMID- 11772307 TI - Review of the molecular genetics and chemotherapeutic treatment of adult and paediatric medulloblastoma. AB - Medulloblastoma is the most common primary brain tumour in children and accounts for 25% of newly diagnosed cases. Recent advances in treatment have extended 5 year survival rates from 3 - > 70% during the past 50 years. These improvements in survival have resulted from a multi-modality approach that includes surgical resection, posterior fossa and craniospinal irradiation and chemotherapy for selected, high-risk patients. The literature regarding chemotherapy of adult and paediatric patients is reviewed in-depth. The most active agents include cisplatin, CCNU, cyclophosphamide, vincristine and carboplatin. Although patients are living longer with their disease, neurocognitive function and quality of life are often impaired following radiation therapy (RT) to the developing brain. To safely allow reductions in the dose of RT, the specificity and efficacy of chemotherapy must be improved. Recent advances in the molecular genetics of medulloblastoma transformation (e.g., myc, PTCH ) are reviewed and discussed. A thorough understanding of these pathways will be critical for the development of more specific, novel drugs. Further clinical trials will be needed to evaluate the activity of these new drugs and determine their role in the treatment plan of patients with medulloblastoma. PMID- 11772308 TI - Farnesyltransferase inhibitors: mechanism and applications. AB - Farnesyltransferase (FT) inhibitors (FTIs) are among the first wave of signal transduction inhibitors to be clinically tested for antitumour properties. FTIs were designed to attack Ras oncoproteins, the function of which depends upon post translational modification by farnesyl isoprenoid. Extensive preclinical studies have demonstrated that FTIs compromise neoplastic transformation and tumour growth. In preclinical models, FTIs display limited effects on normal cell physiology and in Phase I human trials FTIs have been largely well tolerated. Exactly how FTIs selectively target cancer cells has emerged as an important question, one which has become more pressing with the somewhat disappointing results from initial Phase II efficacy trials. Although FTI development was predicated on Ras inhibition, it has become clear that the drugs' antineoplastic properties are based to a large degree on altering the prenylation and function of proteins other than Ras. One key candidate that has emerged is RhoB, an endosomal protein that has been implicated in selective growth inhibition and apoptosis in neoplastic cells. On the basis of mechanistic studies and other recent developments, we propose that FTIs may be useful to treat a unique spectrum of diseases including not only inflammatory breast cancer and melanoma but also non-neoplastic diseases such as diabetic retinopathy and macular degeneration. PMID- 11772309 TI - Protein kinase C inhibitors as novel anticancer drugs. AB - The role of PKC isoforms in signal transduction pathways involved in regulation of the cell cycle, apoptosis, angiogenesis, differentiation, invasiveness, senescence and drug efflux are reviewed, along with the clinical results on the current crop of PKC inhibitors, including midostaurin (PKC-412, CGP 41251, N benzoylstaurosporine), UCN-01 (7-hydroxystaurosporine), bryostatin 1, perifosine, ilmofosine, Ro 31-8220, Ro 32-0432, GO 6976, ISIS-3521 (CGP 64128A) and the macrocyclic bis (indolyl) maleimides (LY-333531, LY-379196, LY-317615). An appreciation of the complex, often contradictory roles of PKC isoforms in signal transduction pathways involved in cancer is important for interpreting the clinical results observed with PKC inhibitors of varying selectivity. An antisense oligonucleotide, ISIS-3521 and two orally available small molecule inhibitors, LY 333531 and midostaurin, have now advanced to latter stage development for cancer and/or other indications. These compounds have varying levels of selectivity for the PKC isoforms and for the kinase and initial safety and early clinical efficacy have been encouraging. At this stage, the potential of PKC inhibition for the treatment of cancer has not been fully realised. The concurrent inhibition of multiple PKC isoforms may yet provide an improved clinical outcome in treating cancers in view of the complex interrelated roles of the PKC isoforms. PMID- 11772310 TI - Telomerase inhibitors for the treatment of cancer: the current perspective. AB - Telomerase is a holoenzyme responsible for the maintenance of telomeres, the protein-nucleic acid complexes at the ends of eukaryotic chromosomes that serve to maintain chromosomal stability and integrity. Telomerase activity is essential for the sustained proliferation of most immortal cells, including cancer cells. Since the discovery that telomerase activity is detected in 85-90% of all human tumours and tumour-derived cell lines but not in most normal somatic cells, telomerase has become the focus of much attention as a novel and potentially highly-specific target for the development of new anticancer chemotherapeutics. Herein we review the current perspective for the development of telomerase inhibitors as cancer chemotherapeutics. These include antisense strategies, reverse transcriptase inhibitors and compounds capable of interacting with high order telomeric DNA tetraplex ("G-quadruplex") structures, so as to prevent enzyme access to the necessary linear telomere substrate. Critical appraisal of each individual approach is provided together with highlighted areas of likely future development. PMID- 11772311 TI - Therapeutic potential of mycobacterial cell wall-DNA complexes. AB - Cell wall skeletons isolated from many bacteria have been shown to possess anticancer activity. The anticancer activities of such preparations have been attributed to the activation of immune effector cells and not to a direct effect on cancer cell division. A cell wall extract from Mycobacterium phlei, wherein mycobacterial DNA in the form of short oligonulceotides is preserved to the cell wall, has anticancer activity against a wide range of cancer cells. Mycobacterial cell wall-DNA complexes (MCC) exert their anticancer activity by a dual mechanism of action: an indirect effect via the induction of anticancer cytokines and a direct effect on cancer cell division mediated by the induction of apoptosis. In this review, the immunomodulatory and the pro-apoptotic mechanisms of action of MCC will be explored. The identification of the active component in MCC will be discussed, as well as the composition differences with cell wall skeletons and live mycobacteria. Finally, the use of MCC against bladder and prostate cancers will be discussed and compared to standard therapies, particularly therapy using mycobacteria and mycobacteria-derived products. PMID- 11772312 TI - Mechanisms of carcinogenesis inhibition by isothiocyanates. AB - Epidemiological studies have suggested that frequent consumption of cruciferous vegetables is associated with a decreased risk in various types of cancer. Cruciferous vegetables are commonly consumed foods that contain organosulfur compounds known as isothiocyanates. These compounds are potent inhibitors of chemically induced carcinogenesis in animals. Extensive work has been conducted to elucidate the mechanisms involved in the inhibition of carcinogenesis by isothiocyanates. These mechanisms include blocking the metabolic activation of the carcinogens by way of altering the enzymes involved in the process, induction of detoxification enzymes and induction of apoptosis. Since their mode of action is selective, the enzyme composition of the tissue and the inhibition or induction of the enzymes by the isothiocyanates will influence their chemopreventive activities. Isothiocyanates may potentially be beneficial in protecting against human carcinogenesis. PMID- 11772313 TI - Critical appraisal of current antithrombotic trials in patients undergoing total hip replacement. AB - Patients undergoing total hip replacement are at high risk of developing venous thromboembolism. The 6th ACCP Consensus Conference on Antithrombotic Therapy identified two effective prophylactic methods; low molecular weight heparins (LMWH) and oral anticoagulants. However, two key issues remain controversial. The relative efficacy and safety of prophylaxis initiated pre operatively and post operatively and the optimum duration of prophylaxis. Clinical practice has diverged in North America and Europe as to the appropriate time to administer prophylaxis. This treatment is given pre-operatively in Europe and post operatively in North America. A number of recent studies have demonstrated that an effective antithrombotic agent administered either immediately before or after surgery may be more effective than current practice. The use of LMWH for extended thromboprophylaxis is supported by convincing data. Clinical trials have demonstrated a significant benefit of pentasaccharide in the prevention of venous thromboembolism in major orthopaedic surgery. A direct thrombin inhibitor given sc. followed by oral administration was found to be as effective and safe as LMWH for the prophylaxis of deep vein thrombosis (DVT) following major hip or knee surgery. PMID- 11772314 TI - Compounds in development to combat hyperphosphataemia. AB - Hyperphosphataemia in haemodialysis patients is associated with secondary hyperparathyroidism and more importantly with an increased cardiovascular mortality in dialysed patients. Removal of phosphate during dialysis is less than net intestinal uptake. This imbalance results in a positive phosphate balance. To control serum phosphate concentration oral phosphate binders have to be taken to reduce net intestinal uptake. The use of classical phosphate binders such as calcium carbonate, calcium acetate and aluminium-containing phosphate binders is limited by their side effects. Hypercalcaemia aggravates vascular calcification and cardiovascular risk. Aluminium intoxication causes aluminium osteopathy, anaemia and encephalopathy. Therefore, the development of calcium- and aluminium free phosphate binders has become a challenge to clinical nephrology. Polyallylamine hydrochloride (sevelamer) is one of the new alternative compounds which has been shown to effectively bind phosphate in dialysis patients. A promising approach in the development of alternative phophate binders are trivalent-iron (Fe(III)) containing phosphate binders. They were not only successfully tested in experimental animals but have also been shown to reduce urinary phosphate excretion and serum phosphate concentrations in patients with preterminal failure and those on maintenance haemodialysis. This review outlines the experimental and clinical data on Fe-III based phosphate binders providing evidence that they will be as effective and safe as phosphate binders without the major side effects of classical phosphate-binding compounds. PMID- 11772315 TI - Botulinum toxin type B: a new injectable treatment for cervical dystonia. AB - Cervical dystonia (CD) causes involuntary muscle spasms and is often associated with pain. Recently, botulinum toxin type B (BTX-B) (Myobloc, Elan South San Francisco, CA, USA) was approved for general use in the treatment of CD in the USA. In two large pivotal trials, BTX-B was found to be safe and effective in decreasing the movements, pain and disability associated with CD. Benefits were noted both in patients who no longer respond and in those who continue to respond to botulinum toxin type A (BTX-A). BTX-B offers an additional therapeutic option for patients with CD. PMID- 11772316 TI - Peginterferon alfa-2a (40 kDa) monotherapy: a novel agent for chronic hepatitis C therapy. AB - Current therapy for hepatitis C remains far from optimal. The modification of IFN by the attachment of a polyethylene glycol (PEG) moiety has produced long-lasting IFNs. A 40 kDa branched peginterferon alfa-2a (40 kDa) (PEG-IFN alfa-2a) has unique pharmacokinetic and pharmacodynamic properties. PEG-IFN alfa-2a is absorbed in a sustained manner and its clearance is reduced substantially compared with IFN alfa-2a, resulting in sustained serum drug concentrations. These constant serum drug levels stay above the EC(50) values (effective concentration 50%) needed for antiviral, antiproliferative and immunomodulatory actions. Sustained virological responses were significantly greater in patients who received PEG-IFN alfa-2a versus IFN alfa-2a, with a similar side effect profile. Histological improvements were seen in patients who achieved sustained virological responses and were frequently observed among patients who did not achieve a virological response. The advantages of PEG-IFN alfa-2a were also seen in patients with cirrhosis or hepatitis C virus (HCV) genotype 1. PMID- 11772317 TI - Update on the therapeutic potential of PDE4 inhibitors. AB - Phosphodiesterase (PDE) enzymes are responsible for the inactiviation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterase 4 (PDE4) is a cAMP specific phosphodiesterase expressed in inflammatory cells such as eosinophils. Inhibition of PDE4 results in an elevation of cAMP in these cells, which in turn downregulates the inflammatory response. The anti-inflammatory effects of PDE4 inhibitors have been well documented both in vitro and in vivo in a range of animal models. The potential use of PDE4 inhibitors as anti-inflammatory agents for the treatment of diseases such as asthma, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS), has received considerable attention from the pharmaceutical industry but to date, there are no selective PDE4 inhibitors on the market. Early PDE4 inhibitors, such as rolipram suffered from dose limiting side effects, including nausea and emesis, which severely restricted their therapeutic utility. Second generation compounds such as cilomilast have been identified with reduced side effect liability. Indeed, cilomilast is showing good therapeutic effects in clinical trials for asthma and COPD and represents the most advanced selective PDE4 inhibitor for any indication. The utility of this class of inhibitor in other inflammatory diseases is less well advanced. However, data in animal models of rheumatoid arthritis (RA) and MS suggests that there is also significant potential for PDE4 inhibitors as treatments for these diseases and the results of clinical trials in these disease areas are eagerly awaited. PMID- 11772318 TI - Mucoactive drugs for asthma and COPD: any place in therapy? AB - Airway mucus hypersecretion is a clinical and pathophysiological feature of a number of severe respiratory conditions, including asthma and chronic obstructive pulmonary disease (COPD). The importance of mucus hypersecretion to the morbidity and mortality of asthma is acknowledged, whereas in COPD it appears to affect only certain groups of patients, particularly the elderly and those prone to chest infections. Treatment with compounds that alter mucus is perceived as a therapeutic option, in particular in continental Europe, and numerous compounds have been developed and are available for clinical use worldwide. However, acceptance (or otherwise) of these drugs in guidelines for management of asthma or COPD has been hampered by lack of information from well designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown and is it likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. Current information indicates that the most effective use of mucolytic drugs is long-term therapy for reduction of exacerbations of COPD. Cost-effective treatment would be in patients with poor lung function who have frequent or prolonged exacerbations or are repeatedly admitted to hospital. PMID- 11772319 TI - Clinical developments for treating ARDS. AB - Acute respiratory distress syndrome (ARDS), is characterised by capillary permeability and pulmonary oedema formation and may complicate a variety of medical and surgical illnesses. As a self-perpetuating state of inflammatory derangement, acute lung injury (ALI)/ARDS is manifest clinically as rapid development of radiographic infiltrates, severe hypoxaemia and reduced lung compliance. Over the years, researchers have made significant progress in elucidating the pathophysiology of this complex syndrome. Therapies targeting specific pathophysiologic steps in the development or persistence of this syndrome are in various stages of laboratory and clinical testing. Results to date have shown nitric oxide (NO) to improve oxygenation in the majority of patients but fail to improve mortality. Surfactant replacement has had limited success in adults, but new formulations and delivery methods may prove beneficial. Several inflammatory mediator-targeted therapies have progressed successfully through early clinical evaluation. Among these, neutrophil elastase inhibitors have shown the most promise and are currently undergoing Phase III trials. Other mediator-targeted therapies, such as prostaglandin E1, IL-10 and platelet activating factor antagonists, have not been found efficacious in large clinical trials of ARDS. However, these therapies, along with coagulation modulators, may have a favourable impact on ARDS by improving outcomes in sepsis, the greatest risk factor for developing this condition. In the interim, supportive care through improvements in mechanical ventilation are beneficial, while specific fluid balance and nutrition strategies may prove advantageous. PMID- 11772320 TI - Antileukotrienes in clinical development for asthma. AB - Asthma is a serious world health problem characterised by a chronic inflammatory disorder of the airways. Asthma attacks, or exacerbations, are episodic but airway inflammation is chronically present. Thus, this disorder requires long term management. The goals of asthma management include prevention steps for long term control, action steps to stop attacks, recognising deteriorating asthma, how to treat deteriorating asthma, how and when to seek medical attention and education. In order to achieve the best therapeutic choice, a stepwise approach should be adopted. In recent years, much progress regarding the characterisation of leukotrienes (LTs) has been achieved. These substances are important products of action of the 5-lipoxygenase (5-LO) enzyme on arachidonic acid (AA) and it has been established that the leukotrienes are key mediators of both allergy and inflammation. Consequently, the important role of the cysteinyl-leukotrienes (Cys LTs) in the pathophysiology of bronchial asthma has been suggested. Pharmacological support for the role of Cys-LTs in asthma has been observed using inhibitors of 5-LO and specific LT receptor antagonists. In the clinical setting, the LT receptor, which plays the most important role, is the Cys-LT1 receptor. The antagonists of this receptor have proven an effective therapy in chronic asthmatics, agonist antigens and exercise-induced bronchoconstriction and in aspirin-intolerant asthmatics. These drugs provide a new approach in asthmatic therapy and therefore may facilitate the compliance of daily therapy. PMID- 11772321 TI - Developments in the treatment of uveitis. AB - Uveitis remains a challenging field to the ophthalmologist as the disease causes significant morbidity and the use of traditional forms of treatment is restricted by limited effectiveness and considerable side effects. This article explores new agents used in the treatment of uveitis as well as the potential of agents used successfully in experimental uveitis. This paper also reviews agents in use for a long time but now used in novel ways. PMID- 11772322 TI - Coagulation inhibitors in the treatment of sepsis. AB - Despite advances in supportive care, sepsis and septic shock continue to be major causes of morbidity and mortality in critically ill patients. The lack of efficacy of anti-inflammatory drugs in patients with sepsis has shifted interest toward developing alternative treatments. The observation that clotting system activation may in part underlie the physiological derangements of sepsis has resulted in efforts to target the clotting cascade as a therapeutic strategy. Anticoagulants have been shown to ameliorate physiological derangements and improve survival in animal sepsis models. Three agents have undergone extensive study in humans: recombinant human activated protein C (rhAPC, drotrecogin alpha), antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI). While a recent Phase III study of rhAPC suggests a survival benefit in patients with sepsis, major concerns about this trial include the manner in which the study was conducted, the potential toxicity of rhAPC and the questionable efficacy of this agent in patients with low mortality risk. Further clinical testing of rhAPC appears to be necessary to better define the target population most appropriate for its use. In contrast, a large Phase III study of high dose ATIII in patients with sepsis failed to show a treatment benefit with this agent. Finally, while TFPI has undergone extensive preclinical and Phase II testing, the results of Phase III studies have not been published. In summary, while coagulation inhibitors may ultimately have a therapeutic role in selected subgroups of patients with sepsis, the efficacy and safety of this class of agents remain to be proven. PMID- 11772323 TI - Advances in the non-surgical treatment of melanoma. AB - Immune responses appear to play a role in the natural history of melanoma and immunotherapy has therefore been the subject of a number of studies. The results of several large randomised studies using allogeneic melanoma vaccines have shown minimal benefit and Phase I/II studies with gene transfected melanoma cells do not appear particularly encouraging. The majority of current interest now centres on development of vaccines using defined melanoma antigens recognised by T-cells and given as dendritic vaccines or injected directly as melanoma peptides or DNA. It can be expected that the most effective antigens and method of administration will become apparent over the next few years. It is clear, however, that melanoma shows low response rates to immunotherapy, as for chemotherapy. Both forms of therapy appear to kill melanoma by induction of apoptosis, so it is possible that resistance to apoptosis may underlie the low responses to these forms of therapy. Much is already known about agents that may sensitise melanoma to apoptosis and combining these with chemotherapy and/or immunotherapy provides a promising new approach in treatment of melanoma. PMID- 11772324 TI - The role of adjuvant therapy for pancreatic cancer. AB - Patients with pancreatic cancer have a very poor outlook. There have been major advances in the standard surgical treatment of this disease, resulting in decreased post-operative mortality and morbidity. The use of chemotherapy and radiotherapy has been developed to increase long-term patient survival following potentially curative resection. The standard chemotherapeutic agent is 5 fluorouracil (5-FU), although newer cytotoxic agents are in clinical trials for advanced cancer. Initial studies of adjuvant therapy have been based on small numbers of patients, but recently two large European randomised controlled trials of adjuvant therapy (EORTC and ESPAC-1) have been completed. These suggest that adjuvant chemotherapy has a significant survival advantage over resection alone but chemoradiotherapy does not. Promising new agents are being developed and tested mainly in clinical trials of advanced pancreatic cancer. The results of large-scale randomised controlled trials to assess adjuvant therapies for pancreatic cancer demonstrate the great surgical and oncological progress that has been made over the past decade. PMID- 11772325 TI - Developing therapies for advanced bladder cancer. AB - Chemotherapy is an indispensable measure in the treatment of invasive or metastatic bladder cancer as even if metastases are not clinically apparent, the majority of cases of invasive bladder cancer are accompanied by micrometastases. At present, MVAC (methotrexate, vinblastine, adriamycin, cisplatin) is the gold standard for bladder cancer chemotherapy. There have consequently been many attempts at MVAC dose-intensification as well as many studies of the feasibility of neoadjuvant chemotherapy using MVAC. Unfortunately, the majority of results from these studies have been negative or contradictory. However, a recent large scale randomised, controlled study yielded more promising results. Evidence has recently emerged which indicates that a useful chemotherapeutic strategy could possibly be devised by adjusting the dose and timing of MVAC. Increasing effort is also being put into the development of new gold standards for bladder cancer chemotherapy based on the use of newly developed antitumour drugs, and a number of candidates have emerged. It is hoped that the future we will see successful establishment of a number of useful regimens as a result of Phase III clinical studies using MVAC as their control regimen. For example, both gemcitabine and the taxanes, in combination with other drugs, are strong candidates for this purpose. The ultimate therapeutic strategy for bladder cancer will be a therapeutic approach which permits conservation of the bladder even when the malignancy is invasive and steady progress is already being made toward this goal, in limited cases, by means of multidisciplinary treatment. PMID- 11772326 TI - The use of ranolazine in cardiovascular disease. AB - Ranolazine is a novel drug that has shown promise in the treatment of cardiovascular disease. Ranolazine exerts its effect by shifting myocardial energy metabolism away from free fatty acids and toward glucose as the substrate for production of adenosine triphosphate. Preclinical data have confirmed that ranolazine reduces myocardial ischaemic injury in various animal models. Researchers are continuing to gather clinical data but findings to date support the conclusion that ranolazine has anti-ischaemic effects without inducing the typical reduction in blood pressure and heart rate associated with the use of traditional anti-ischaemic agents. Given the absence of haemodynamic effects associated with ranolazine, it has great promise as a drug that could be added to existing therapy without concern for hypotensive or bradycardic side effects. Ranolazine has been shown to improve exercise-induced myocardial ischaemia and to lessen the severity of angina in the setting of chronic ischaemic heart disease. Early preclinical observations also suggest positive effects of ranolazine in the management of congestive heart failure; however, trials in this area are ongoing. Several recently completed Phase III clinical studies in patients with chronic ischaemic heart disease have confirmed the findings of smaller trials and should satisfy regulatory concerns necessary to place ranolazine on the commercial market in the US. The maker of ranolazine, CV Therapeutics (Palo Alto, California), will file a New Drug Application (NDA) with the US FDA for the approval of ranolazine as an anti-anginal in the near future. PMID- 11772327 TI - Rosuvastatin: a highly efficacious statin for the treatment of dyslipidaemia. AB - Rosuvastatin is a synthetic enantiomer that is hepatoselective, relatively hydrophilic and has minimal metabolism via the cytochrome P450 3A4 system (similar to pravastatin). Rosuvastatin, like atorvastatin, has a plasma half-life of about 20 h and is a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The majority of HMG-CoA reductase inhibitory activity in plasma is associated with the parent rosuvastatin compound. In a Phase II study, rosuvastatin across a dose range of 1- 80 mg lowered low-density lipoprotein cholesterol (LDL-C) by 34 - 65%. Phase III trials have demonstrated greater reductions in LDL-C for rosuvastatin compared to atorvastatin as well as greater increases in high-density lipoprotein cholesterol (HDL-C). The drug appears to be well tolerated at all doses up to 80 mg/day. A starting dose of 10 mg will reduce LDL-C by approximately 50%, which should adequately treat most patients to within the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) goals. PMID- 11772328 TI - Management of growth retardation in the young patient with Crohn's disease. AB - Linear growth retardation is a major complication of Crohn's disease that occurs in children. It is related both to undernutrition and to direct effects of the inflammatory process on the growth axis. Enteral nutrition (elemental, semi elemental or polymeric diet) employed as the sole source of nutrition remains a mainstay of treatment of active Crohn's disease because it corrects nutritional deficits, has anti-inflammatory effects, heals mucosal inflammation and stimulates growth. Conventional corticosteroids have adverse effects on growth and preliminary data suggest that an ileal-release preparation of budesonide may also suppress linear growth. 6-Mercaptopurine (6-MP) and its prodrug azathioprine maintain remission in children with Crohn's disease. These treatments thus have the potential to improve growth velocity and final adult height. PMID- 11772329 TI - Emerging treatments for irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a functional GI disorder that is associated with abdominal discomfort and altered bowel habits. It accounts for up to 28% of patients presenting to a gastroenterology practice and poses a significant personal, societal and economic burden internationally. The Manning, Rome I and Rome II criteria were developed to identify appropriate IBS patients for entry into IBS studies in a consistent manner. Refinements in the understanding of the physiology of the enteric nervous system (ENS), which controls motility, secretion and sensation, provided the basis for our comprehension of the pathophysiology of IBS. Visceral hypersensitivity and neurotransmitter imbalance currently receive the most attention as possible mechanisms of IBS. This article outlines conventional treatments and reviews the data on emerging and experimental therapies for IBS. Emerging therapies for IBS using 5-HT mediation include 5-HT(3) antagonists, such as ondasetron, granisetron and alosetron, as well as 5-HT(4) agonists such as tegaserod and prucalopride. In addition to opioid agonists (e.g. fedotozine) several other drugs that act on other ENS receptors are being studied. In spite of significant progress in IBS research, these emerging therapies require more studies before they can be utilised as clinical treatments. PMID- 11772330 TI - Dehydroepiandrosterone for the treatment of systemic lupus erythematosus. AB - The adrenal steroidal hormone dehydroepiandrosterone (DHEA) has been studied as a potential pharmacological agent in the treatment of the autoimmune disease systemic lupus erythematosus (SLE). Both the endocrine effects (the ability to be converted peripherally to androgenic and oestrogenic sex steroids) and the immunomodulatory effects of DHEA (the production of the Th(1) cytokines, such as IL-2) suggest that this hormone could be of benefit for patients with SLE. During the past decade, five controlled clinical trials and a number of additional observational studies have been performed investigating these possibilities. The results from these studies suggest that 200 mg/day of DHEA for 7 - 12 months decreases corticosteroid requirement for the patients, the frequency of disease flares, has an anti-osteoporotic effect and has an overall beneficial effect on SLE disease activity in female patients. A small study suggested benefits for cognitive function in such patients. The side effects acne and hirsutism were seen relatively frequently (30 - 40% and 10 - 12% of patients, respectively) but in most instances were deemed mild. DHEA treatment resulted in changes in lipid profile and may have endocrine effects, the consequences of which will need to be ascertained through longer-term follow-up studies. PMID- 11772331 TI - The role of leukotriene inhibitors in allergic rhinitis and paranasal sinusitis. AB - Leukotrienes (LTs) have been known in the field of immunology since the 1930s. At that time they were referred to as the slow reacting substance of anaphylaxis. However, they were not characterised until the 1980s, when they were noted to be formed during the breakdown of arachidonic acid (AA) by the enzyme 5-lipoxygenase (5-LO). There are five types of LT: LTA(4), LTB(4), LTC(4), LTD(4) and LTE(4). LTs are so called because the molecules were originally isolated from leukocytes and their carbon backbones contain 3 double bonds in series (a trion). This structural information provided the key to the oxidative pathway of lipometabolism, known as the 5-LO pathway. LTs are classified as inflammatory mediators. They are produced by a number of cell types, particularly mast cells, eosinophils, basophils, macrophages and monocytes. With the identification disorders associated with inflammatory pathways, such as asthma, allergic rhinitis and paranasal sinusitis, the LTs have been implicated in the pathogenesis of these conditions and have become targets for therapeutic modulation. In this review we will look at the biological effects of LTs, how they are formed, their role in asthma patients, the first therapeutic use of LT inhibitors and finally LTs with reference to the paranasal sinus areas. PMID- 11772332 TI - Pharmacotherapy of primary CNS lymphoma. AB - Primary CNS lymphoma (PCNSL) is distinguished from other brain tumours by its striking response to chemotherapy. Surgery has little role (if any) in the treatment of PCNSL. Radiation therapy has been proven to prolong survival but its use is complicated by delayed neurological toxicity, particularly among the elderly. Progress in understanding the physiology of the blood-brain barrier (BBB) and the pharmacology of chemotherapeutic agents has substantially improved the treatment and prognosis of this disease. The single most effective agent is methotrexate (MTX). The goal of delivering an adequate dose of MTX to the brain and the cerebrospinal fluid (CSF) has been achieved by a variety of strategies, including systemic high dose, intra-arterial injection following pharmacological disruption of the BBB and intrathecal (it.) administration. MTX-based combination chemotherapy has yielded the best results to date but the prognosis of patients with PCNSL remains significantly worse than comparable patients with systemic non Hodgkin's lymphoma (NHL). Ongoing trials continue to test novel combinations of agents, doses and improved routes of delivery with the hope of improving disease control and diminishing treatment-related neurotoxicity. PMID- 11772334 TI - Oxcarbazepine. AB - Oxcarbazepine is one of the recently introduced anti-epileptic drugs (AEDs) in the US. This drug has demonstrated efficacy as adjunctive therapy in adults and children, and as monotherapy in adults for the treatment of seizures of partial onset. There is also convincing evidence of its efficacy in patients with newly diagnosed and refractory trigeminal neuralgia. In addition, the initial efficacy results of oxcarbazepine in other neuropathic pain conditions and in bipolar disorders are encouraging. In this review, recommendations on the optimal clinical use of oxcarbazepine are given based on its pharmacokinetic profile, efficacy and tolerability in those various conditions. PMID- 11772333 TI - Valacyclovir in the treatment of genital herpes and herpes zoster. AB - Genital herpes is prevalent and sometimes debilitating. Likewise, herpes zoster ('shingles') can be painful and often disabling. The treatment of these conditions has been advanced over the past two decades by the introduction of guanosine nucleoside antivirals such as valacyclovir (Valtrex), Glaxo Wellcome), the highly bioavailable prodrug of acyclovir (Zovirax), Glaxo Wellcome). This review describes the pharmacology, pharmacokinetics, clinical efficacy and tolerability of valacyclovir and considers its clinical attributes in the context of those of the antivirals, acyclovir and famciclovir (Famvir), SmithKline Beecham). The data demonstrate that valacyclovir is more effective than placebo and as effective as other antivirals in the episodic and suppressive treatment of recurrent genital herpes. Valacyclovir is the only antiviral shown to be effective with a short (3-day) course in the episodic treatment of recurrent genital herpes, as well as with once-daily dosing for daily suppressive therapy. In herpes zoster, valacyclovir is as effective as famciclovir and more effective than either placebo or acyclovir at facilitating cutaneous healing and healing of zoster-associated pain and post-herpetic neuralgia. Valacyclovir is well tolerated, with convenient dosing frequencies for the treatment of genital herpes or herpes zoster, it also has the option for use as a short course therapy in the episodic treatment of recurrent genital herpes, all of which are important benefits in the management of these conditions. PMID- 11772335 TI - The nature of an ideal therapeutic human antibody. PMID- 11772336 TI - HSP90 as a new therapeutic target for cancer therapy: the story unfolds. AB - Current anticancer drug development strategies involve identifying novel molecular targets which are crucial for tumourigenesis. The molecular chaperone heat shock protein (HSP) 90 is of interest as an anticancer drug target because of its importance in maintaining the conformation, stability and function of key oncogenic client proteins involved in signal transduction pathways leading to proliferation, cell cycle progression and apoptosis, as well as other features of the malignant phenotype such as invasion, angiogenesis and metastasis. The natural product HSP90 inhibitors geldanamycin and radicicol exert their antitumour effect by inhibiting the intrinsic ATPase activity of HSP90, resulting in degradation of HSP90 client proteins via the ubiquitin proteosome pathway. Anticancer selectivity may derive from the simultaneous combinatorial effects of HSP90 inhibitors on multiple cancer targets and pathways. 17-allylamino, 17 demethoxygeldanamycin (17AAG), a geldanamycin derivative, showed good activity and cancer selectivity in preclinical models and has now progressed to Phase I clinical trial in cancer patients with encouraging initial results. Phase II trials including combination studies with cytotoxic agents are now being planned and these should allow the therapeutic activity of 17AAG to be determined. Second generation HSP90 inhibitors may be designed to overcome some of the drawbacks of 17AAG, including limited oral bioavailability and solubility. They could also be engineered to target specific functions of HSP90, which may not only provide greater molecular selectivity and clinical benefit but may also increase understanding of the complex functions of this molecular chaperone. HSP90 inhibitors provide proof of concept for drugs directed at HSP90 and protein folding and this principle may be applicable to other medical conditions involving protein aggregation and stability. PMID- 11772337 TI - Tissue-engineered skin substitutes. AB - The last two years have seen new tissue-engineered skin substitutes come onto the market and begin to resolve the various roles to which each is best suited. It is becoming evident that some of the very expensive cell-based products have cost benefit advantage despite their high price and are valuable within the restricted applications for which they are intended. The use of skin substitutes for testing purposes has extended from epidermal keratinocytes to other integumentary epithelia and into preparations containing multiple cell types in which reactions resulting from paracrine interactions can be examined. Challenges remain in the application of gene therapy techniques to skin substitutes, both the control of transgene expression and in the selection of suitable genes to transfect. A coming challenge is the production of tissue-engineered products without the use of animal products other than human cells. A challenge that may be diminishing is the importance of acute rejection of allogeneic tissue-engineered skin substitutes. PMID- 11772338 TI - Dendritic cell maturation in active immunotherapy strategies. AB - Dendritic cells (DCs) loaded with tumour antigen have become the centrepiece of clinical trials testing active immunotherapy strategies. Important variables include the source of DCs, the choice of antigens, the method of antigen loading and the route and timing of administration. Recently, the requirement for and the method of, DC maturation have been receiving particular attention. This is due to observations from in vitro studies and animal models demonstrating that mature DCs induce more potent antigen-specific T-cells responses than immature DCs. Furthermore, preliminary observations in human studies suggest that immature DCs might actually downregulate antigen-specific T-cell responses but mature DCs may augment them. Current studies are addressing how to define DC maturation, whether the variety of methods for maturation result in DCs with similar T-cell stimulatory capacity, how to maintain the maturational status and whether maturation in vitro before immunisation, or in vivo, after immunisation, results in better DC function. PMID- 11772339 TI - Photodynamic therapy: applications in dermatology. AB - Photodynamic therapy (PDT) offers the potential of an effective new treatment in several areas of medicine. Topical photodynamic therapy is practical and non invasive and is particularly suited to dermatological indications. A variety of pre-malignant and malignant skin lesions including Bowen's disease, actinic keratoses (AKs) and basal cell carcinoma (BCC) have been treated with success. The role of PDT in inflammatory dermatoses remains to be established. The currently available literature is reviewed. PMID- 11772340 TI - Adoptive T-cell therapy for the treatment of solid tumours. AB - Solid tumours can be eradicated by infusion of large amounts of tumour-specific T cells in animal models. The successes seen in preclinical models, however, have not been adequately translated to human disease due, in part, to the inability to expand tumour antigen-specific T-cells ex vivo. Polyclonality and retention of antigen-specificity are two important properties of infused T-cells that are necessary for successful eradication of tumours. Investigators are beginning to evaluate the impact of attempting to reconstitute full T-cell immunity representing both major T-cell subsets, cytolytic T-cells and T-helper (Th) cells. One of the more important and often overlooked steps of successful adoptive T-cell therapy is the ex vivo expansion conditions, which can dramatically alter the phenotype of the T-cell. A number of cytokines and other soluble activation factors that have been characterised over the last decade are now available to supplement in vitro antigen presentation and IL-2. Newer molecular techniques have been developed and are aimed at genetically altering the characteristics of T-cells including their antigen-specificity and growth in vivo. In addition, advanced imaging techniques, such as positron emission tomography (PET), are being implemented in order to better define the in vivo function of ex vivo expanded tumour-specific T-cells. PMID- 11772341 TI - Targeting approaches to oral drug delivery. AB - Delivery of pharmaceuticals, particularly biotechnology products such as proteins, peptides, genes, oligonucleotides and vaccines, via the oral route remains problematic to this day. Instability in the gastrointestinal environment and poor permeability across the intestinal epithelial cell barrier contribute to poor oral bioavailability for many of these compounds. Current targeting strategies to overcome these issues are focused on three-part systems in which the drug (i) is loaded into a protective particulate carrier (ii) which is coated with target-specific ligands (iii) which mediate site-specific delivery of the drug-carrier complex. Protection from gastrointestinal degradative processes combined with site-specific delivery to absorptive regions of the intestinal tract is purported to yield high local concentrations of the drug of choice in close proximity with the epithelial cell layer and hence, transport across that barrier through a variety of mechanisms. This review examines the impact of cutting-edge technologies such as genomics and combinatorial chemistry on targeted oral drug delivery strategies. The explosion in rate of identification of new targets using genomics, together with high-throughput screening for target specific ligands using combinatorial chemistry and phage display, has the potential to revolutionise this field. Particular reference is made to advances associated with targeted delivery of vaccines to M-cells or antigen-presenting cells in gut-associated lymphoid tissues. PMID- 11772342 TI - The efficacy of genetic vaccination is dependent upon the nature of the vector system and antigen. AB - Genetic immunisation is emerging as a safe and specific means of eliciting prophylactic and therapeutic immune responses. Just as the immune response to various infectious agents will differ based on the aetiology of the infection and nature of antigenic determinants, so does the immune response following genetic immunisation. This review will discuss the impact of vector selection and antigen structure on genetic immunisation. Comparative analyses of plasmid DNA (pDNA), adenovirus (Ad) and vaccinia virus vaccines have demonstrated that each vector system is associated with a unique outcome following immunisation. Similarly, re targeting cytosolic protein to different cellular compartments can dramatically affect the subsequent immune response. Thus, to design an effective genetic vaccine, one must consider both the biology of the vaccine vector/antigen combination and the biology of the pathogen. PMID- 11772343 TI - Meningococcal serogroup C conjugate vaccine. AB - Meningococcal meningitis and septicaemia are important causes of morbidity and mortality in many parts of the world. More than 90% of the cases are caused by serogroups A, B and C; the remaining 10% are largely caused by the W-135 and Y strains. During the mid-to-late 1990s there was an increase in meningococcal serogroup (MS) C disease in the UK and some parts of Europe. MS C polysaccharide vaccines that were developed in the 1960s are weakly immunogenic and not protective in infants under 2 years of age, but are effective in older recipients. Meningitec (Wyeth-Ayerst) is produced by conjugation of serogroup C oligosaccharide with a mutant diphtheria protein (CRM197), with the aim of inducing T-cell dependent immune responses. It has been found to be immunogenic in infants, toddlers, older children and adults. The vaccine has also been shown to induce immunological memory and therefore is likely to give long-term protection against disease. It received a license for use in the UK in October 1999 and was introduced into the UK immunisation schedule in November 1999. Surveillance studies after introduction of this and similar vaccines have demonstrated a dramatic fall in the incidence of MS C disease. Pre-licensure research studies and post-licensure adverse event data have confirmed that the vaccine is safe. PMID- 11772344 TI - Rituximab: clinical development and future directions. AB - The availability of effective monoclonal antibodies (mAbs) has revolutionised the management of patients with B-cell malignancies. The most widely studied of these agents is rituximab (Rituxan, IDEC Pharmaceuticals, San Diego, CA), a chimeric anti-CD20 antibody. Using the standard 4-weekly administration schedule, rituximab induces responses in almost half of patients with relapsed follicular/low-grade (F/LG) non-Hodgkin's lymphoma (NHL) with complete remissions in 6%. Lower response rates (RRs) have been noted in chronic lymphocytic leukaemia (CLL) using the standard dose and schedule. The drug has been well tolerated in most patients with common adverse events including mild to moderate fevers and chills and rare occurrences of a serious syndrome related to cytokine release and rapid tumour clearance. This antibody is also active against aggressive NHL, mantle cell NHL, post-transplant lymphoproliferative disorder (PTLD), lymphoplasmacytic NHL and hairy cell leukaemia and is also being evaluated in autoimmune disorders. Combinations of rituximab with chemotherapy regimens such as CHOP (cyclophosphamide, adriamycin, vincristine, predinisone) may alter the therapeutic paradigm for these diseases. The future promise of this antibody is a foundation on which to develop new strategies to increase the cure of patients with lymphoid malignancies. PMID- 11772345 TI - Elemental mercury poisoning in a family of seven. AB - Mercury poisoning in children is rare but may have devastating health consequences when exposure is unrecognized. Mercury occurs in three forms: elemental, inorganic, and organic. Elemental mercury (Hg(0)) vapor may become volatile following an accidental spill and may be readily absorbed from the lungs. The following case study describes how the poison center, health department, physicians, and others worked together to treat a family with long term exposure to elemental mercury vapor in the home. Identification and prevention of this type of exposure in the community are discussed. PMID- 11772346 TI - Kids need clean air: air pollution and children's health. AB - Air pollution affects children's health in many ways, including reduced lung function, increased morbidity, increased use of health care services, and infant mortality. Information on the relationship of air pollution and children's health is discussed, with a focus on the diversity of research methods used to understand this relationship. Decisions affecting air quality ultimately are made through political and social processes. Health care and health promotion practitioners who are concerned about the health of children should provide leadership for advocacy to promote environmental health in our communities. PMID- 11772347 TI - Childhood cancer and environmental toxins: the debate continues. AB - Despite its rarity and advances in treatment and supportive care, cancer remains the leading cause of death from disease in children under 15. While the field of pediatric oncology has seen some advances in diagnostic and treatment techniques, researchers continue to face numerous hurdles in determining causative factors associated with childhood cancer. One of the most hotly contested issues in this area is the possible link between childhood cancer and environmental toxins. This article presents an interview with three pediatric oncologists and an environmental research toxicologist to help provide insight into the relationship between environmental exposures and childhood cancer. PMID- 11772348 TI - Appendix A: chronology of children's environmental health. PMID- 11772350 TI - Lipodystrophy study results. PMID- 11772351 TI - The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. AB - Artemisinin, the endoperoxide sesquiterpene lactone produced by the Chinese medicinal herb Artemisia annua, is very difficult to synthesise. Moreover, its production by mean of cell, tissue or organ cultures is very low. Presently, only its extraction from cultivated plants is viable. A large variation in artemisinin content has been observed in the leaves of plants from different origins. The genetic basis of this variation has been assessed and evidence for a quantitative inheritance of the artemisinin concentration presented. Additive genetic components were predominant, resulting in a high narrow-sense heritability estimate. Thus, goods results can be expected from mass selection for the breeding of lines of Artemisia annua rich in artemisinin. Yet, dominance variance is also present in the total genetic variability, indicating that crosses between selected genotypes should generate progenies with particularly high artemisinin content. As a matter of fact, selection and crossing, in wild populations, of genotypes with high artemisinin concentration resulted in hybrid lines containing up to 1.4 % artemisinin (on dry leaves basis). PMID- 11772352 TI - Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action. AB - The discovery that the sesquiterpene peroxide yingzhaosu A (13) and 1,2,4 trioxane artemisinin (14) are active against chloroquine-resistant strains of Plasmodium falciparum, has opened a new era in the chemotherapy of malaria. In vitro and in vivo tests with synthetic structurally simpler trioxanes clearly demonstrate that much of the skeleton of 14 is redundant and that chirality is not required for activity. In addition, structure-activity relations and the search for the pharmacophore reveal that high antimalarial activity can be displayed by molecules which do not resemble the geometry of 13 and 14 at all. The possible mode of action of 13, 14, and synthetic peroxides is examined. They are believed to kill intraerythrocytic Plasmodium by interacting with the heme discarded by proteolysis of ingested hemoglobin. Complexation of heme with the peroxide bond followed by electron transfer generates an oxy radical that evolves to the ultimate parasiticidal agent. Experiments with ferrous reagents indicate that active peroxides including 14 and its congeners kill the parasite by alkylation with a sterically non-encumbered C-centered radical. However, another possibility is the involvement of a Fe(IV)=O species as the toxic agent. The review covers our own and other contributions to this timely topic and evaluates the different mechanisms proposed for the mode of action of peroxidic antimalarials. PMID- 11772353 TI - New trends in extraction, identification and quantification of artemisinin and its derivatives. AB - Artemisinin, a sesquiterpene lactone endoperoxide, and a number of its precursors, metabolites and semisynthetic derivatives have shown to possess antimalarial properties. Several methods have been reported for the measurement of artemisinin and its main derivatives in plant material and biological fluids. However, most of them are either not sufficiently sensitive and do not offer reliable results, or are difficult to apply in routine analyses. Therefore, new methods for the determination of these compounds, such as supercritical fluid extraction and chromatography, pressurized solvent extraction, microwave-assisted extraction, high-performance liquid chromatography coupled to mass spectrometry or evaporative light scattering detection, will be presented. Applications to plant material, pharmaceutical formulations and biological fluids will also be reviewed. PMID- 11772354 TI - Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites. AB - Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importance. At present, there is no vaccine available, and chemotherapy is the cornerstone of schistosomiasis control. Praziquantel is the drug of choice. Oxamniquine has become difficult to obtain and metrifonate has recently been withdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for prevention and cure of schistosomiasis. Significant progress has been made with artemether, the methyl ether of dihydroartemisinin, already widely used for the treatment of malaria. The present article reviews the literature that led to the development of artemether for chemoprophylaxis in schistosomiasis, and it summarises the experiences so far obtained with its use to control schistosomiasis in different endemic settings. Topics covered include an overview of the global burden of schistosomiasis and approaches for its control; the nature and features of artemisinin and related derivatives, initially discovered as antimalarials, other bioactivities, and their recent discovery of antischistosomal properties; a historic account disclosing the antischistosomal activity of artemether; in vivo assessment of drug susceptibility of different developmental stages of schistosome parasites; artemether-induced pathology evidenced by scanning and transmission electron microscopy; the possible mechanism of action; in vivo studies with combination therapy of artemether and praziquantel; results of randomised controlled clinical trials of oral artemether for the prevention of patent infection and morbidity; and, ultimately the translation of this knowledge into public health action in different endemic settings towards a more integrated approach of schistosomiasis control. PMID- 11772355 TI - Radiolabelled tracers and anticancer drugs for assessment of therapeutic efficacy using PET. AB - Positron Emission Tomography (PET) has the potential to improve efficacy of established and novel cancer therapies and to assist more rapid and rational progression of promising novel therapies into the clinic. This is due to PET's unrivalled sensitivity and ability to monitor the pharmacokinetics and pharmacodynamics of drugs and biochemicals radiolabelled with short -lived positron emitting radioisotopes. PET is a multidisciplinary science which employs chemists, biologists, mathematical modellers, pharmacologists as well as clinicians. Clinical research questions in oncology determine the methodological challenges faced by these other disciplines. Within this context we focus on the developments of the radiolabelled compounds that have underpinned the clinical work in oncology for monitoring tumour and normal tissue pharmacokinetics, assessment of tumour response, cell proliferation, gene expression, hypoxia, multidrug resistance and status of receptors on tumours. PMID- 11772356 TI - Enzyme-targeted, nucleoside-based radiopharmaceuticals for scintigraphic monitoring of gene transfer and expression. AB - Enzymes, the expression products of transferred or native genes, offer unique windows of opportunity for clinical diagnosis and therapy. Although some expression products can be monitored in plasma, nuclear medicine imaging (SPECT and PET) offers the unique ability to selectively measure the intensity and regional/spatial distribution of gene expression both in vivo, in situ. Importantly, the superior sensitivity and moderate spatial resolution of the nuclear techniques also enable in vivo kinetic characterization of enzyme substrate interaction. Indeed, the non-invasive, whole-body assessment of gene expression can only be achieved through imaging techniques. Given today's technology, nuclear imaging techniques uniquely provide the necessary sensitivity required to evaluate the success of the gene delivery and expression (transcription and translation), and to detect unwanted expression by non-target tissues. Enzymes are a special class of proteinacious gene expression products that selectively bind specific substrates for the purpose of molecular biotransformation rather than for signal transduction. In general, enzymes have received much less attention for imaging than receptors and antibodies, despite the enzymes' high substrate specificity and the potential for kinetic evaluation. Enzymes are attractive targets for diagnostic imaging and radioisotope radiotherapy because they convert multiple molecular copies of the substrate (radiotracer) per molecule of enzyme, thereby greatly increasing the ultimate sensitivity relative to the sensitivity offered by receptors that bind with 1:1 stoichiometry. Not surprisingly, enzymes have been the preferred molecular targets to date for scintigraphic imaging of gene therapy. This overview describes opportunities and advances in the utilization of radiolabelled nucleosides and nucleoside bases for imaging in gene therapy, with emphasis on the exploitation of enzyme systems for scintigraphic imaging of gene expression in gene therapy of cancer. Herpes simplex virus type-1 thymidine kinase and bacterial/fungal cytosine deaminase are discussed within the context of gene therapy issues such as gene vectors for targeting and delivery, the bystander effect, and radionucleoside delivery. The utilization of nucleosides as markers of tissue proliferation is discussed with respect to selected enzyme targets. PMID- 11772357 TI - PET studies with carbon-11 radioligands in neuropsychopharmacological drug development. AB - A basic problem in the discovery and development of novel drugs to be used in the treatment of neurological and psychiatric disorders is the absence of relevant in vitro or in vivo animal models that can yield results which can be extrapolated to man. Drug research now benefits from the fast development of functional imaging techniques such as positron emission tomography (PET) which trace radiolabelled molecules directly in the human brain. PET uses molecules that are labelled with short-lived radionuclides and injected intravenously into experimental animals, human volunteers or patients. The most frequent approach is to study how an unlabelled drug inhibits specific binding of a well characterised selective PET radioligand. The alternative direct approach is to radiolabel a new potential drug and to trace its uptake, anatomical distribution and binding in brain. Furthermore, the effects of a novel drug on physiological-biochemical parameters, such as glucose metabolism or blood flow, can also be assessed. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action, to correlate pharmacological and physiological effects, and to optimise clinical treatment. PMID- 11772358 TI - Use of bromine-76 and iodine-123 radiohalogenated tracers in the drug development process. AB - The only bromine and iodine radioisotopes worth using in PET or SPECT in vivo investigations during the development of a new drug are 76Br and 123I. It is most of the time impossible to isotopically label a drug with 76Br or 123I since the occurrence of drugs having a bromine or an iodine atom within their chemical structure is quite limited. However, by using specific radiobrominated or radioiodinated probes, it is possible to study in vivo the potential interaction of a drug with biochemical processes such as blood flow, glucose consumption, protein synthesis or cell proliferation and neurotransmission. Radiobrominated and radioiodinated probes have been described mainly for assessing cell proliferation. For imaging various classes of specific binding sites involved in neuronal or hormonal transmission, a great number of radiohalogenated ligands have been proposed and validated. The two-steps strategy consists of performing an "in vivo assay" by using first of all, one of these specific radio-brominated/ iodinated ligands (or probes) for targeting specific binding sites (receptor, transporter, enzymes) and in a second step by assessing the interaction of the cold drug on the binding of these probes. This indirect observation of drug receptor (transporter, enzyme) occupancy allows predicting response, optimum dose and optimum scheduling. The most important radiobrominated and radioiodinated ligands specific for dopaminergic, serotoninergic, cholinergic and gabaergic binding sites and their application in drug development processes are reviewed. PMID- 11772359 TI - Instrumentation and methodology for quantitative pre-clinical imaging studies. AB - Radiotracer imaging studies performed on animals have the potential to play a major role in pharmaceutical development, pharmacology studies and basic biochemistry research. Recent developments in instrumentation and imaging methodology make it possible to image and quantify the kinetics of radiolabelled pharmaceuticals in a wide range of animal models from rodents to non-human primates. This article reviews the developments which have led to the current state-of-the-art, including advances in detector technologies, image reconstruction and tracer kinetic modelling. The practical issues specific to animal imaging studies are also discussed. With appropriate instrumentation and rigorous methodology, quantitative pre-clinical imaging has an important role to play in drug development. PMID- 11772390 TI - Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin-proteasome dependent proteolysis in cancer and septic rats. AB - The development of new pharmacological approaches for preventing muscle wasting in cancer is an important goal because cachectic patients display a reduced response to chemotherapy and radiotherapy. Xanthine derivatives such as pentoxifylline inhibit tumour necrosis factor-alpha (TNF) production, which has been implicated in the signalling of muscle wasting. However, the effect of pentoxifylline has been inconclusive in clinical trials. We report here the first direct evidence that daily injections of torbafylline (also known as HWA 448), another xanthine derivative, had no effect by itself on muscle proteolysis in control healthy rats. In cancer rats, the drug blocked the lipopolysaccharide induced hyperproduction of TNF and prevented muscle wasting. In these animals HWA 448 suppressed the enhanced proteasome-dependent proteolysis, which is sensitive to the proteasome inhibitor MG132, and the accumulation of high-molecular-mass ubiquitin (Ub) conjugates in the myofibrillar fraction. The drug also normalized the enhanced muscle expression of Ub, which prevails in the atrophying muscles from cancer rats. In contrast, HWA 448 did not reduce the increased expression of either the 14 kDa Ub conjugating enzyme E2 or the ATPase and non-ATPase subunits of the 19 S regulatory complex of the 26 S proteasome, including the non-ATPase subunit S5a, which recognizes polyUb degradation signals. Finally, the drug also prevented muscle wasting in septic rats (which exhibit increased TNF production), and was much more potent than pentoxifylline or other xanthine derivatives. Taken together, the data indicate that HWA 448 is a powerful inhibitor of muscle wasting that blocks enhanced Ub-proteasome-dependent proteolysis in situations where TNF production rises, including cancer and sepsis. PMID- 11772391 TI - Endothelial nitric oxide synthase activity is linked to its presence at cell-cell contacts. AB - The enzyme endothelial nitric oxide synthase (eNOS) is essential for vascular integrity. Many studies have demonstrated a link between the localization and activity of eNOS. Here, we studied the influence of cell-cell contact on this link in the microvascular endothelial bEnd.3 cell line. By immunofluorescence microscopy, eNOS localization at the plasma membrane was found to be dependent on cell-cell contact. In particular, eNOS was highly enriched at the intercellular contact sites. Further analysis showed that the pattern of eNOS localization at the plasma membrane resembled that of PECAM-1 (platelet endothelial cell adhesion molecule 1), but not that of the adherens junction proteins VE (vascular endothelial)-cadherin and plakoglobin. eNOS that was localized at the contact sites was, in part, Triton X-100-insoluble, in contrast with eNOS at the Golgi complex, which may indicate an association of eNOS with the actin cytoskeleton. Interestingly, eNOS activity was up-regulated in confluent monolayers compared with subconfluent cells, while there was no difference in eNOS expression. This correlation between cell confluence and eNOS activity was also found when primary bovine aortic endothelial cells were studied. These data imply that cell-cell contact induces the localization of eNOS at intercellular junctions, which is required for agonist-induced eNOS activation. PMID- 11772392 TI - Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. AB - The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA-CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA binding site or with exogenous ADA resulted in a significant reduction (50-70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA-CD26 interaction in the lymphocyte-epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA-CD26 interaction in cell to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA-CD26 interaction on the cell surface has a role in lymphocyte-epithelial cell adhesion. PMID- 11772393 TI - Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation. AB - cDNA species coding for novel variants of cyclic-AMP-specific phosphodiesterases (PDEs), namely the PDE7B family, were isolated from rats and characterized. Rat PDE7B1 (RNPDE7B1) was composed of 446 amino acid residues. Rat PDE7B2 (RNPDE7B2) and PDE7B3 (RNPDE7B3), which possessed unique N-terminal sequences, consisted of 359 and 459 residues respectively. Northern hybridization analysis showed that rat PDE7B transcripts were particularly abundant in the striatum and testis. PCR analyses revealed that rat PDE7B2 transcripts were restricted to the testis and that low levels of PDE7B3 transcripts were expressed in the heart, lung and skeletal muscle. In situ hybridization analysis demonstrated that rat PDE7B transcripts were expressed in striatal neurons and spermatocytes. In spermatocytes, rat PDE7B transcripts were expressed in a stage-specific manner during spermatogenesis. The K(m) values of recombinant rat PDE7B1, PDE7B2 and PDE7B3 for cAMP were 0.05, 0.07 and 0.05 microM respectively. Each rat PDE7B variant was the most sensitive to 3-isobutyl-1-methylxanthine (IC(50) 1.5-2.1 microM). Two phosphorylation sites for cAMP-dependent protein kinase (PKA) were found in rat PDE7B1 and PDE7B3, whereas rat PDE7B2 possessed one site. PKA dependent phosphorylation was observed in C-terminal phosphorylation sites of three rat PDE7B variants, in addition to unique N-terminal regions of rat PDE7B1 and PDE7B3. Unique tissue distribution and PKA-dependent phosphorylation of PDE7B variants suggested that each variant has a specific role for cellular functions via cAMP signalling in various tissues. PMID- 11772394 TI - abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans. AB - Two genes encoding the ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptide, abf-1 and abf-2, were identified in Caenorhabditis elegans. Recombinant ABF-2 exhibited potent microbicidal activity against Gram positive and Gram-negative bacteria, and yeasts. The tissue-specific distribution estimated by immunofluorescence staining and transgenic analysis of a gfp fusion gene (where GFP corresponds to green fluorescent protein) suggested that ABF-2 contributes to surface defence in the pharynx. abf-1 contains a single intron at a conserved position, suggesting that asabf and abf originated from a common ancestor. Both transcripts for abf-1 and abf-2 were detected as two distinct forms, i.e. spliced leader (SL)1-trans-spliced with a long 5'-untranslated region (UTR) and SL-less with a short 5'-UTR. A polycistronic precursor RNA encoding ABF 1 and ABF-2 was detected, suggesting that these genes form an operon. An 'opportunistic operon' model for regulation of abf genes, including the generation of short SL-less transcripts, is proposed. In conclusion, C. elegans should have an immune defence system due to the antimicrobial peptides. C. elegans can be a novel model for innate immunity. Furthermore, the combination of biochemical identification in Ascaris suum and homologue hunting in C. elegans should be a powerful method of finding rapidly evolved proteins, such as some immune-related molecules in C. elegans. PMID- 11772395 TI - The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs. AB - Point mutations in the human fibroblast growth factor (FGF) receptor 3 gene (Fgfr3) produce a constitutively active receptor, which disrupts chondrocyte differentiation in the growth plate and results in skeletal dysplasias with severe shortening of the limbs. Alternative splicing of the Fgfr3 transcript gives rise to two isoforms, IIIc and IIIb, which vary in their specificity for FGF ligands. We examined the expression of these FGFR3 isoforms in the bovine fetal rib growth plate to determine whether levels of FGFR3 expression are zone related. Transcripts for both Fgfr3 isoforms are expressed in rib growth plate, with maximum expression in the hypertrophic region and the least expression in the reserve zone. Fgfr3 IIIc is the predominant isoform in the growth plate. Western-blot analysis revealed the presence of full-length FGFR3 (135 kDa) for both isoforms in the reserve zone, a major 98 kDa fragment in all zones and smaller fragments primarily in the hypertrophic zone. Immunostaining localized FGFR3 to the pericellular region of reserve chondrocytes and to the extracellular matrix in the hypertrophic zone. These results suggest that the transmembrane form of FGFR3 increasingly undergoes proteolytic cleavage towards the hypertrophic zone to produce an extracellular-domain fragment of FGFR3, which is present in large amounts in the matrix of hypertrophic cells. These findings suggest a proteolytic regulatory mechanism for FGFR3, whereby Fgfr3 fragments could control availability of FGF for the intact receptor, and by which proteolysis could inactivate the receptor. PMID- 11772396 TI - Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes. AB - The Rho GDP dissociation inhibitor (RhoGDI) regulates the activation-inactivation cycle of Rho small GTPases, such as Cdc42 and RhoA, by extracting them from the membrane. To study the roles of Mg(2+), phosphatidylinositol 4,5-bisphosphate (PIP(2)), ionic strength and phosphorylation on the interactions of RhoGDI with Cdc42 and RhoA, we developed a new, efficient and reliable method to produce prenylated Rho proteins using the yeast Saccharomyces cerevisiae. It has been previously reported that protein kinase A (PKA)-treatment of isolated membranes increased RhoA extraction from membranes by RhoGDI [Lang, Gesbert, Delespine Carmagnat, Stancou, Pouchelet and Bertoglio (1996) EMBO J. 16, 510-519]. In the present study, we used an in vitro affinity chromatography system to show that phosphorylation of RhoA and Cdc42 significantly increased their interaction with RhoGDI under physiological conditions of ionic strength. This increase was independent of the nucleotide (GDP or guanosine 5'-[gamma-thio]triphosphate) loaded on to the Rho proteins, as well as of Mg(2+) and PIP(2). Moreover, dephosphorylation of rat brain membranes by alkaline phosphatase significantly decreased the extraction of RhoA and Cdc42 by RhoGDI. Subsequent re phosphorylation by PKA restored the extraction levels, indicating the reversibility of this process. These results clearly demonstrate that the phosphorylation states of Cdc42 and RhoA regulate their interactions with RhoGDI and, consequently, their extraction from rat brain membranes. We therefore suggest that phosphorylation is a mechanism of regulation of Cdc42 and RhoA activity that is independent of GDP-GTP cycling. PMID- 11772397 TI - Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction. AB - Protein kinase C (PKC)-theta, a member of the 'novel' subfamily of PKC isoforms, is of singular importance in transducing signals in T-lymphocytes. Since understanding of regulatory phosphorylation of novel PKCs is fragmentary and inconsistent with findings for 'classical' PKC isoforms, we investigated three potential phosphorylation sites on PKC-theta; in the activation loop (Thr(538)), turn motif (Ser(676)) and hydrophobic motif (Ser(695)). Combined evidence from phospho-specific antisera and MS demonstrates phosphorylation at all three sites. Unlike its closest paralogue, PKC-delta, lack of negative charge in the activation loop of PKC-theta results in a profound catalytic defect (>100-fold reduction in the T538A mutant); the high sequence similarity between PKC-theta and -delta assists in the formulation of structural hypotheses to account for this major difference. In contrast with mechanisms proposed for other PKC isoforms, phosphorylation at the other two sites does not reconstitute catalytic activity. Activation loop phosphorylation is critical in vivo, since the T538A mutant completely lost its capacity to mediate T-cell receptor-stimulation of nuclear factor kappaB (NF-kappaB) activation in Jurkat T-cells. Hydrophobic motif phosphorylation also substantially influences PKC-theta catalytic activity (5 fold reduction in the S695A mutant), but does not impair NF-kappaB activation in Jurkat T-cells. Its mechanism is independent of secondary effects on activation loop phosphorylation and cannot be explained by thermal instability. Turn motif phosphorylation has a limited effect on kinase activity, but negatively regulates other aspects of PKC-theta function, since the S676A mutant is more efficient than wild-type in inducing NF-kappaB activation in Jurkat T-cells. These findings expand our understanding of the roles of phosphorylation in novel PKCs, and indicate that PKC-theta is a constitutively competent kinase as a consequence of constitutive phosphorylation of its activation loop. PMID- 11772398 TI - Expression of 5-lipoxygenase in pulmonary artery endothelial cells. AB - Increased expression of 5-lipoxygenase (5LO) in pulmonary artery endothelial cells (PAECs) has been observed in disease states such as pulmonary hypertension and allergen challenge. To understand the function of endothelial 5LO, we examined the expression of this enzyme in normally cultured human PAECs and its characteristics when overexpressed. A small amount of 5LO message and protein was detected by reverse-transcriptase-mediated PCR (RT-PCR) and Western blotting in PAECs. Sequencing of the RT-PCR products that overlapped the entire coding region of 5LO mRNA indicated that the sequence of PAEC 5LO was identical with that of leucocyte 5LO. Incubation of the PAECs with A23187 and arachidonic acid led to a small production of 5-hydroxyeicosatetraenoic acid (5-HETE) (46-98 pmol/4x10(6) cells) but no leukotrienes. Overexpression of 5LO in PAECs by adenovirus-mediated gene transfer revealed that the enzyme was localized in the nucleus. Incubation of the transduced cells with A23187 (5 microM) caused the production of both 5LO products and downstream leukotrienes. The proportions of the produced leukotriene A(4) (LTA(4)) hydrolates (sum of 6-trans-LTB(4) and 12-epi-6-trans-LTB(4)), LTB(4) and cysteinyl leukotriene were approx. 17:14:10. cGMP production in the 5LO-transduced PAECs was decreased by 33+/-14% on stimulation with A23187. These results show that cultured PAECs express a minimal amount of 5LO, which can generate some 5-HETE, but not leukotrienes. However, increased expression of 5LO in PAECs can lead to the production of all downstream leukotrienes, which could potentially cause endothelial dysfunction in the pulmonary vasculature. PMID- 11772399 TI - Sarcolipin uncouples hydrolysis of ATP from accumulation of Ca2+ by the Ca2+ ATPase of skeletal-muscle sarcoplasmic reticulum. AB - Sarcolipin (SLN) is a small peptide found in the sarcoplasmic reticulum of skeletal muscle. It is predicted to contain a single hydrophobic transmembrane alpha-helix. Fluorescence emission spectra for the single Trp residue of SLN suggest that SLN incorporates fully into bilayers of dioleoylphosphatidylcholine, but only partially into bilayers of phosphatidylcholines with long (C(22) or C(24)) fatty acyl chains. The fluorescence of SLN is quenched in bilayers of dibromostearoylphosphatidylcholine, also consistent with incorporation into the lipid bilayer. SLN was reconstituted with the Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum. Even at a 50:1 molar ratio of SLN/ATPase, SLN had no significant effect on the rate of ATP hydrolysis by the ATPase or on the Ca(2+) dependence of ATP hydrolysis. However, at a molar ratio of SLN/ATPase of 2:1 or higher the presence of SLN resulted in a marked decrease in the level of accumulation of Ca(2+) by reconstituted vesicles. The effect of SLN was structurally specific and did not result from a breakdown in the vesicular structure or from the formation of non-specific ion channels. Vesicles were impermeable to Ca(2+) in the absence of ATP in the external medium. The effects of SLN on accumulation of Ca(2+) can be simulated assuming that SLN increases the rate of slippage on the ATPase and the rate of passive leak of Ca(2+) mediated by the ATPase. It is suggested that the presence of SLN could be important in non shivering thermogenesis, a process in which heat is generated by hydrolysis of ATP by skeletal-muscle sarcoplasmic reticulum. PMID- 11772400 TI - Signal- and importin-dependent nuclear targeting of the kidney anion exchanger 1 binding protein kanadaptin. AB - Kanadaptin (kidney anion exchanger adaptor protein) has recently been identified as a protein with binding activity to the cytoplasmic domain of the kidney Na(+) independent Cl(-)/HCO(-)(3) anion exchanger 1 (kAE1). Since it is widely expressed in tissues devoid of kAE1, however, kanadaptin is likely to have additional cellular roles. This is supported by its multidomain structure, and possession of three clusters of basic amino acids exhibiting similarity to known nuclear localization sequences (NLSs). In the present study, we use immunofluorescence and subcellular fractionation approaches to demonstrate that kanadaptin is localized within the nuclei of various epithelial and non epithelial cultured cell types. The role of the different NLSs is examined in transfection studies using plasmids encoding full-length kanadaptin with or without green fluorescent protein (GFP) as a fusion tag, as well as truncation derivatives thereof. Strong nuclear localization of fusion proteins containing amino acids 140-230 of kanadaptin, which include the sequence AVSRKRKA(193) (NLS1) was observed. Substitution of Arg(191) with a threonine residue resulted in a cytoplasmic location of the expressed protein, while NLS1 proved sufficient to target an otherwise cytoplasmically localized beta-galactosidase-GFP fusion protein to the nucleus. Using a direct binding assay we show that a fusion protein containing kanadaptin amino acids 1-231 (but not the Thr(191) substituted derivative) is recognized with nM affinity by the conventional NLS-binding importin alpha/beta heterodimer. Nuclear import studies on microinjected and permeabilized rat hepatoma cells demonstrated functionality of the NLS in nuclear targeting, with inhibition by antibodies demonstrating the requirement of both importin alpha and beta for nuclear import of kanadaptin. That kanadaptin possesses a functional importin-alpha/beta-recognized NLS explains the nuclear localization of kanadaptin in various cultured cell types, and opens up the possibility that kanadaptin may have a signalling role in the nucleus. PMID- 11772401 TI - Glycoprotein IIb-IIIa-dependent aggregation by glycoprotein Ibalpha is reinforced by a Src family kinase inhibitor (PP1)-sensitive signalling pathway. AB - It has been proposed that the receptor for von Willebrand factor (vWF), glycoprotein (GP)Ib-IX-V, signals through the same pathway as the collagen receptor, GPVI, namely via Src kinases, the Fc receptor (FcR) gamma-chain and Syk, leading to tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2). The aim of the present study was to assess the functional significance of this pathway in platelet activation by GPIb-IX-V. In washed platelets, vWF/ristocetin and vWF/botrocetin stimulate weak tyrosine phosphorylation of the FcR gamma chain, Syk and PLCgamma2, but not the adaptor LAT (linker for activation of T cells), which is localized to glycolipid-enriched membrane domains. Increases in tyrosine phosphorylation were blocked by the Src family kinase inhibitor, 4-amino 5-(4-chlorophenyl)-7-(t-butyl)pyrazolo-d-3,4-pyrimidine (PP1). Under the same conditions, neither stimulus induced activation of PLCgamma2 nor functional responses, such as Ca(2+) elevation, secretion or GPIIb-IIIa-dependent aggregation. In contrast, in platelet-rich plasma (PRP), threshold concentrations of ristocetin or asialo-vWF stimulated GPIb-dependent biphasic aggregation, in which the second phase was blocked by PP1. Importantly, a significant component of the initial phase and the complete second phase of aggregation was blocked by GPIIb-IIIa receptor antagonists in PRP. Higher concentrations of ristocetin stimulated GPIIb-IIIa-independent agglutination in PRP. These results demonstrate that GPIb-IX-V initiates activation of GPIIb-IIIa in PRP through an undefined pathway that is reinforced by a PP1-sensitive pathway. In contrast, activation of GPIbalpha in washed platelets does not promote functional responses. PMID- 11772402 TI - Equilibrium unfolding studies of the rat liver methionine adenosyltransferase III, a dimeric enzyme with intersubunit active sites. AB - The reversible unfolding of rat liver methionine adenosyltransferase dimer by urea under equilibrium conditions has been monitored by fluorescence spectroscopy, CD, size-exclusion chromatography, analytical ultracentrifugation and enzyme activity measurements. The results obtained indicate that unfolding takes place through a three-state mechanism, involving an inactive monomeric intermediate. This intermediate has a 70% native secondary structure, binds less 8-anilinonaphthalene-1-sulphonic acid than the native dimer and has a sedimentation coefficient of 4.24+/-0.15. The variations of free energy in the absence of denaturant [DeltaG(H(2)O)] and its coefficients of urea dependence (m), calculated by the linear extrapolation model, were 36.15+/-2.3 kJ.mol(-1) and 19.87+/-0.71 kJ.mol(-1).M(-1) for the dissociation of the native dimer and 14.77+/-1.63 kJ.mol(-1) and 5.23+/-0.21 kJ.mol(-1).M(-1) for the unfolding of the monomeric intermediate respectively. Thus the global free energy change in the absence of denaturant and the m coefficient were calculated to be 65.69 kJ.mol( 1) and 30.33 kJ.mol(-1).M(-1) respectively. Analysis of the calculated thermodynamical parameters indicate the instability of the dimer in the presence of denaturant, and that the major exposure to the solvent is due to dimer dissociation. Finally, a minimum-folding mechanism for methionine adenosyltransferase III is established. PMID- 11772403 TI - Kinetic study of various binding modes between human DNA polymerase beta and different DNA substrates by surface-plasmon-resonance biosensor. AB - The interaction of a series of DNA substrates with human DNA polymerase beta has been studied in real time by using a surface-plasmon-resonance (SPR) biosensor technique. We have prepared the sensor surfaces comprising different DNA targets, including single-stranded DNA, blunt-end double-stranded DNA, gapped DNA and DNA template-primer duplexes containing various mismatches at different positions. The binding and dissociation of polymerase beta at the DNA-modified surfaces was measured in real time, and the kinetics profiles of polymerase-DNA interaction were analysed using various physical models. The results showed that polymerase beta binding to single-stranded DNA (K(A)=1.25 x 10(8) M(-1); where K(A) is the equilibrium affinity constant) was thermodynamically more favourable than to blunt-end DNA duplex (K(A)=7.56x10(7) M(-1)) or gapped DNA (K(A)=8.53x10(7) M( 1)), with a single binding mode on each DNA substrate. However, polymerase beta bound to DNA template-primer duplexes (15 bp with a 35 nt overhang) at two sites, presumably one at the single-strand overhang and the other at the 3'-end of the primer. When the DNA duplex was fully matched, most of the polymerase beta (83%) bound to the template-primer duplex region. The introduction of different numbers of mismatches near the 3'-end of the primer caused the binding affinity and the fraction of polymerase beta bound at the duplex region to decrease 8-58-fold and 15-40%, respectively. On the other hand, the affinity of polymerase beta for the single-strand overhang remained unchanged while the fraction bound to the single strand region increased by 15-40%. The destabilizing effect of the mismatches was due to both a decrease in the rate of binding and an increase in the rate of dissociation for polymerase beta. PMID- 11772404 TI - Characterization and spatiotemporal expression of orchestin, a gene encoding an ecdysone-inducible protein from a crustacean organic matrix. AB - We report the characterization of a new gene encoding an acidic protein named Orchestin. This protein is a component of the organic matrix of calcium storage structures (calcareous concretions) elaborated during the moulting cycles of the terrestrial crustacean Orchestia cavimana. The deduced molecular mass of Orchestin is estimated to be 12.4 kDa and the pI to be 4.4, whereas the native protein extracted from the calcium deposits migrates as a 23 kDa band on SDS/PAGE. This discrepancy is probably due to the richness of this protein in acidic amino acids (approx. 30%). The protein obtained by expressing the Orchestin cDNA in Escherichia coli presents an electrophoretic mobility of 25 kDa. Antibodies raised against the recombinant protein recognize the 23 kDa native protein exclusively among the organic-matrix components. Spatiotemporal analysis of the expression of the orchestin gene shows that it is expressed only in the storage organ cells when the concretions are elaborated during the premoult period and also, to a smaller extent, during the postmoult period. The translation products are expressed in accordance with the transcript expression during both the premoult and postmoult periods. Study of the hormonal stimulation of orchestin reveals that 20-hydroxyecdysone induces this gene as a secondary response or late-response gene. PMID- 11772405 TI - Promoter activity of the 5'-flanking regions of medaka fish soluble guanylate cyclase alpha1 and beta1 subunit genes. AB - We examined the spatial expression pattern of medaka fish (Oryzias latipes) soluble guanylate cyclase alpha(1) and beta(1) subunit genes, OlGCS-alpha(1) and OlGCS-beta(1), and characterized the 5'-flanking region required for expression of both genes by introducing various promoter-luciferase fusion-gene constructs into COS-1 cells and medaka fish embryos. The OlGCS-alpha(1) and OlGCS-beta(1) gene transcripts were detected in whole brain and kidney in 7-day and 9-day embryos. Primer-extension analysis demonstrated that there were no differences among various adult organs (brain, eye, kidney, ovary and testis) in the transcription start site of the OlGCS-alpha(1) and OlGCS-beta(1) genes. Neither gene contained the functional TATA box within its 5'-flanking region, and the basal promoter activity was found between nucleotides +33 and +42 in the OlGCS alpha(1) gene and between nucleotides +146 and +155 in the OlGCS-beta(1) gene. In the assay of medaka fish embryos, the 5'-flanking region of the OlGCS-beta(1) gene exhibited lower promoter activity than that of the OlGCS-alpha(1) gene. In the experiments on dual-luciferase fusion-gene constructs, the 5'-flanking region of the OlGCS-alpha(1) gene connected to the 5'-flanking region of the OlGCS beta(1) gene was introduced into medaka fish embryos, and the 5'-flanking regions of both subunit genes were shown to mutually influence each other's promoter activity. PMID- 11772406 TI - Characterization of monoclonal antibodies against Escherichia coli core RNA polymerase. AB - Multiple interactions with DNA, RNA and transcription factors occur in a transcription cycle. To survey the proximity of some of these factors to the Escherichia coli RNA polymerase surface, we produced a set of nine monoclonal antibodies (mAbs) against the enzyme. These mAbs, located at different places on the surface of the enzyme, were used in a co-immunopurification assay to investigate interference with the binding of NusA, sigma70, GreB and HepA to core RNA polymerase. One of these mAbs turned out to be the first antibody inhibitor of the binding of NusA and sigma70; it did not affect GreB and HepA interactions. Its epitope was located on the beta' subunit at the C-terminus of region G. The properties of this mAb reinforce the idea that the mutually exclusive binding of NusA and sigma70 to core RNA polymerase is due to, at least partially, overlapping binding sites, rather than allosteric interaction between two distant binding sites. This mAb is also useful to understand the occupancy of sigma70, NusA and Gre proteins on core RNA polymerase. PMID- 11772407 TI - Pre-steady-state phosphorylation and dephosphorylation of detergent-purified plasma-membrane Ca2+-ATPase. AB - Pre-steady-state phosphorylation and dephosphorylation of purified and phospholipid-depleted plasma-membrane Ca(2+)-ATPase (PMCA) solubilized in the detergent polyoxyethylene 10 lauryl ether were studied at 25 degrees C. The time course of phosphorylation with ATP of the enzyme associated with Ca(2+), probably the true phosphorylation reaction, showed a fast phase (k(app) near 400 s(-1)) followed by a slow phase (k(app)=23 s(-1)). With asolectin or acidic phosphatidylinositol, the concentration of phosphoenzyme (EP) increased at as high a rate as before, passed through a maximum at 4 ms and stabilized at a steady level that was approx. half that without lipids. Calmodulin (CaM) did not change the rate of the fast phase, accelerated the slow phase (k(app)=93 s(-1)) and increased [EP] with small changes in the shape of the time course. Dephosphorylation was slow (k(app)=30 s(-1)) and insensitive to CaM. Asolectin accelerated dephosphorylation, which followed biexponential kinetics with fast (k(app)=220 s(-1)) and slow (k(app)=20 s(-1)) components. CaM stimulated the fast component by nearly 50%. The results show that the behaviour of the PMCA is complex, and suggest that acidic phospholipids and CaM activate PMCA through different mechanisms. Acceleration of dephosphorylation seems relevant during activation of the PMCA by acidic phospholipids. PMID- 11772408 TI - Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages. AB - Metallothionein (MT) is a low-molecular-mass, cysteine-rich metal binding protein thought to be involved in the detoxification of heavy metals and scavenging of free radicals. MT is directly induced not only by heavy metals, but also by hormones and cytokines. The present study, which uses mice with genetic deletions of the MT proteins (MT(-/-) mice), was designed to evaluate the effects of MT on the expression of pro-inflammatory cytokines in macrophages. We found that the production of tumour necrosis factor (TNF) induced by lipopolysaccharide (LPS) in peritoneal macrophages is up-regulated by MT via the modulation of nuclear factor kappaB (NF-kappaB) activity. This conclusion is supported by the following observations: (1) LPS stimulated the secretion of less TNF activity from MT(-/-) peritoneal exudate macrophages (PEMs) than from wild-type controls (MT(+/+) mice) without a difference in the pattern of kinetics; (2) LPS-stimulated expression of TNF-alpha mRNA was decreased in MT(-/-) PEMs; (3) LPS-stimulated activation of NF kappaB was decreased in MT(-/-) PEMs; and (4) production of TNF in PEMs of MT(-/ ) mice after LPS treatment in vivo was decreased (compared with MT(+/+) PEMs). Expression of other inflammatory cytokines, interleukin (IL)-1alpha and IL-6 mRNA, which were modulated by NF-kappaB, were also down-regulated in MT(-/-) PEMs. Thus MT plays a key role in the LPS-induced activation of PEMs via the modulation of NF-kappaB activity. PMID- 11772410 TI - A novel cycling assay for cellular cADP-ribose with nanomolar sensitivity. AB - cADP-ribose (cADPR) is a novel cyclic nucleotide derived from NAD(+) that has now been established as a general Ca(2+) messenger in a wide variety of cells. Despite the obvious importance of monitoring its cellular levels under various physiological conditions, its measurement has been technically difficult and requires specialized reagents. In this study a widely applicable high-sensitivity assay for cADPR is described. ADP-ribosyl cyclase normally catalyses the synthesis of cADPR from NAD(+), but the reaction can be reversed in the presence of high concentrations of nicotinamide, producing NAD(+) from cADPR stoichiometrically. The resultant NAD(+) can then be coupled to a cycling assay involving alcohol dehydrogenase and diaphorase. Each time NAD(+) cycles through these coupled reactions, a molecule of highly fluorescent resorufin is generated. The reaction can be conducted for hours, resulting in more than a thousand-fold amplification of cADPR. Concentrations of cADPR in the nanomolar range can be measured routinely. The unique ability of ADP-ribosyl cyclase to catalyse the reverse reaction provides the required specificity. Using this assay, it is demonstrated that cADPR is present in all tissues tested and that the levels measured are directly comparable with those obtained using a radioimmunoassay. All the necessary reagents are widely available and the assay can be performed using a multiwell fluorescence plate reader, providing a high-throughput method for monitoring cADPR levels. This assay should be valuable in elucidating the messenger role of cADPR in cells. PMID- 11772409 TI - Differential induction of mafF, mafG and mafK expression by electrophile-response element activators. AB - The three small Maf proteins, MafF, MafG and MafK, have been implicated in a number of physiological processes, including development, differentiation, haematopoiesis and stress response. Here we report the constitutive expression of mafF, mafG and mafK in six human cell lines derived from various tissues (HepG2, IMR-32, K-562, HEK-293, RD and A549). The expression patterns of mafF, mafG and mafK varied widely among cell lines. Because small Maf proteins have been implicated in electrophile response element (EpRE)-mediated stress response, the ability of three EpRE activators [pyrrolidinedithiocarbamate (PDTC), phenylethyl isothiocyanate (PEITC) and t-butylhydroquinone (tBHQ)] to induce small Maf expression was examined in detail in HepG2 cells. Both PDTC and PEITC induced mafF, mafG and mafK expression, whereas tBHQ failed to markedly induce any of the three small Mafs. Where a response was observed, mafF was induced to the greatest extent compared with mafG and mafK, and this response was transcriptionally mediated. PDTC also induced small Maf expression in the other cell lines examined, with patterns of induction varying among cell lines. The differences in expression among the cell lines examined, coupled with the induction patterns observed, indicate that the three small maf genes are stress-responsive, but may be regulated via differing mechanisms. Furthermore, the fact that tBHQ, PDTC and PEITC induce EpRE activity, but that tBHQ fails to markedly induce any of the small Mafs, suggests that up-regulation of small Mafs is not an absolute requirement for EpRE-mediated gene expression. PMID- 11772411 TI - Characterization and regulation of inositol monophosphatase activity in Mycobacterium smegmatis. AB - Mycobacterium tuberculosis and related members of the genus Mycobacterium contain a number of inositol-based lipids, such as phosphatidylinositol mannosides, lipomannan and lipoarabinomannan. The synthesis of phosphatidylinositol in M. smegmatis is essential for growth and myo-inositol is a key metabolite for mycobacteria. Little is known about the biosynthesis of inositol in mycobacteria and the only known de novo pathway for myo-inositol biosynthesis involves a two step process. First, cyclization of glucose 6-phosphate to afford myo-inositol 1 phosphate via inositol-1-phosphate synthase and, secondly, dephosphorylation of myo-inositol 1-phosphate by inositol monophosphatase (IMP) to afford myo inositol. The following report examines IMP activity in M. smegmatis extracts, with regard to pH dependence, bivalent cation requirement, univalent cation inhibition, regulation by growth and carbon source. We show that IMP activity, which is optimal at the end of the exponential growth phase in Sauton's medium, is Mg(2+)-dependent. Moreover, IMP activity is inhibited by Li(+) and Na(+), with Li(+) also being able to inhibit growth of M. smegmatis in vivo. This study represents a first step in the delineation of myo-inositol biosynthesis in mycobacteria. PMID- 11772412 TI - Chicken ovalbumin upstream-promoter transcription factor and E-box-binding proteins enhance thyroid-hormone responsiveness of the malic enzyme gene in avian hepatocytes. AB - In chick embryo hepatocytes (CEH), stimulation of malic enzyme transcription by 3,3',5-tri-iodothyronine (T3) is mediated by a liver-specific and T3-inducible DNase I hypersensitive region (-3910 to -3640 bp) in the malic enzyme gene. Previous studies have shown that this region contains a cluster of five T3 response elements (T3REs), referred to as a T3 response unit (T3RU), plus three accessory elements that enhance T3 responsiveness conferred by the T3RU. Here we report the identification of two additional accessory elements within the -3910 to -3640 bp region. Each element augments T3 regulation of malic enzyme transcription in CEH. One element, designated region G (-3681/-3666 bp), contains a single nuclear-hormone-receptor half-site that binds the orphan receptor chicken ovalbumin upstream-promoter transcription factor. The other element, designated region H (-3655/-3646 bp), contains an E-box motif that binds proteins of unknown identity. Stimulation of T3RE function by region G or region H does not require the presence of additional malic enzyme sequences. In contrast with the stimulatory effects of regions G and H on T3 responsiveness in CEH, neither of these elements is effective in modulating T3 responsiveness in chick embryo fibroblasts (CEF). Instead, region H functions as a T3-insensitive repressor of transcription in CEF. These results indicate that chicken ovalbumin upstream promoter transcription factor and E-box-binding proteins interact with nuclear T3 receptors to enhance T3 regulation of malic enzyme transcription in CEH and that alterations in region G and region H activities contribute to diminished T3 regulation of malic enzyme transcription in CEF relative to CEH. As the pattern of protein binding to regions G and H varies substantially between CEH and CEF, the mechanism for cell-type-dependent differences in region G and region H activity may involve alterations in protein binding to these T3 accessory elements. PMID- 11772413 TI - Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12. AB - FK506-binding protein (FKBP12) is highly expressed in neuronal tissue, where it is proposed to localize calcineurin to intracellular calcium-release channels, ryanodine receptors and Ins(1,4,5)P(3) receptors (InsP(3)Rs). The effects of FKBP12 on ryanodine receptors have been well characterized but the nature and function of binding of FKBP12 to InsP(3)R is more controversial, with evidence for and against a tight interaction between these two proteins. To investigate this, we incorporated purified type-1 InsP(3)R from rat cerebellum into planar lipid bilayers to monitor the effects of exogenous recombinant FKBP12 on single channel activity, using K(+) as the current carrier. Here we report for the first time that FKBP12 causes a substantial change in single-channel properties of the type-1 InsP(3)R, specifically to increase the amount of time the channel spends in a fully open state. In the presence of ATP, FKBP12 can also induce co ordinated gating with neighbouring receptors. The effects of FKBP12 were reversed by FK506. We also present data showing that rapamycin, at sub-optimal concentrations of Ins(2,4,5)P(3), decreases the rate of calcium release from cerebellar microsomes. These results provide evidence for a direct functional interaction between FKBP12 and the type-1 InsP(3)R. PMID- 11772414 TI - Evolution of maurotoxin conformation and blocking efficacy towards Shaker B channels during the course of folding and oxidation in vitro. AB - Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide bridges that acts on various K(+) channels, including the voltage-gated Shaker B subtype. In the present study, we have investigated over 80 h: (1) the time course of folding of synthetic MTX (sMTX) by CD analysis; (2) the kinetics of disulphide bridge formation by MS; and (3) the potency of MTX in blocking Shaker B currents during the combined process of its in vitro folding and oxidation. From the CD data, we show that stable secondary structures of sMTX evolve sequentially over time, with the appearance of the alpha-helix within 5 h, followed by the formation of the beta-sheet within 22 h. Using MS analysis, the sMTX intermediates were also found to appear sequentially from the least (one disulphide-bridged sMTX) to the most oxidized species (native-like, four disulphide-bridged sMTX). The time course of formation of secondary structures coincides mainly with the occurrence of one-disulphide-bridged sMTX for the alpha helix and two- or three-disulphide-bridged sMTX for the beta-sheet. On-line electrophysiological recordings, which measure sMTX blocking efficacy on K(+) currents during its folding and oxidation, were performed on Shaker B channels expressed in Xenopus oocytes. Unexpectedly, the results demonstrate that sMTX is highly potent at the initial stage of oxidation, whereas its blocking activity can be transiently and dramatically reduced at later stages during the course of folding/oxidation before it reaches full bioactivity. These data suggest that formation of disulphide bridges can both physically stabilize and alter the bioactive three-dimensional structure of sMTX. PMID- 11772415 TI - Lipid lowering in acute coronary syndromes: new evidence, new questions. PMID- 11772416 TI - Patients with acute coronary syndromes should received statins. PMID- 11772417 TI - Lipoprotein changes with statins. AB - The effects of statins and other lipid drugs are assessed by their ability to affect specific lipid fractions. Although there has been a great deal written abut the statins, most recent papers have focused on the comparative effects of the statins on triglycerides and high-density lipoprotein cholesterol, or have been concerned with the nonlipid effects of these drugs. In addition, some recent papers have focused on new parameters that may mediate cardiovascular risk, such as high-sensitivity C-reactive protein. PMID- 11772418 TI - Statins in homozygous familial hypercholesterolemia. AB - Homozygous familial hypercholesterolemia is a rare disorder resulting in severe premature atherosclerosis. Drug therapy was previously viewed as inadequate for control of the dyslipidemia, so portacaval shunting, plasmapheresis, and liver transplantation were undertaken to treat this condition. Despite these drastic measures, additional cholesterol-lowering treatment may still be required. Furthermore, there is a need for pharmacologic control until additional measures can be undertaken. The statins, an evolving class of cholesterol-modifying drugs, represent a significant development in the treatment of homozygous familial hypercholesterolemia. The experience with statins in this condition is limited, but some insight into their utility has been gained from studies reviewed in this article. It is recommended that high doses of statins be used in combination with other lipid-modifying strategies for the best control of the dyslipidemia of homozygous familial hypercholesterolemia. PMID- 11772419 TI - Goals of statin therapy: three viewpoints. AB - The "lipid hypothesis" is now universally recognized as a law. Few issues in medicine are as completely resolved as the question of whether reducing serum cholesterol increases longevity. However, there are a few questions that remain, and the most important uncertainty is to what extent cholesterol should be reduced. The medical community, in partnership with government and industry, has contributed many excellent trials demonstrating the effects in patients with elevated cholesterol (above the mean). Where should our goal of therapy be? Until data is available from several large, ongoing trials, we do not have a final answer. We asked three investigators, Drs. Gilbert Thompson, Christopher Packard, and Neil Stone, who have all been integrally involved in the accumulation of our present database, to argue three different possible answers. PMID- 11772420 TI - A general assessment of the safety of HMG CoA reductase inhibitors (statins). AB - Few principles in medicine today are as well accepted as the benefits of using statins to reduce cardiovascular risk factors and to prevent cardiovascular disease. The recent withdrawal of a statin (cerivastatin) has lead to a re examination of all statins, and an attempt to better assess the risk-benefit ratio of this class of drugs. Although the benefits of statin treatment are well known from a myriad of clinical trials, the safety of these compounds has not been an issue since lovastatin was first introduced in 1987. This report provides a brief review of statin safety, and reiterates the excellent profile of this class of drugs. PMID- 11772421 TI - Statins and inflammatory markers. AB - Inflammation is involved in the initiation and progression of atherosclerosis and the development of atherosclerotic events. Understanding of the molecular basis of inflammation has led to the identification of markers that may be important new targets in atherothrombotic disease. Inflammatory markers, such as cell adhesion molecules, cytokines, and high-sensitivity C-reactive protein, have been shown to predict future cardiovascular events in individuals with and without established disease. 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, or statins, inhibit the synthesis of cholesterol and have been demonstrated to reduce cardiovascular morbidity and mortality. Recently, statins have been shown to modulate several of the mechanisms of inflammation in atherosclerosis in vitro and in vivo, including reduction of inflammatory markers in clinical trials. In this article, we briefly review the biology, epidemiology, and clinical trial data on the effects of statins on some of the more promising inflammatory markers. PMID- 11772422 TI - Risk factor modification through weight loss enhanced with pharmacotherapy. PMID- 11772423 TI - Postmenopausal hormone replacement therapy as antiatherosclerotic therapy. AB - Cardiovascular disease remains the number one killer of women. Although important for the reduction of cardiovascular events, lipid alteration does not appear to be sufficient to obtain optimum reduction in cardiovascular risk. Women have a potential opportunity for further reduction in cardiovascular risk through postmenopausal hormone replacement therapy. More than 50 observational studies indicate that postmenopausal use of hormone replacement therapy reduces atherosclerosis and cardiovascular events. However, recently reported, randomized, controlled clinical trials have yielded mixed results as to whether hormone replacement therapy reduces cardiovascular events relative to placebo. These, as well as other randomized controlled trials of hormone replacement therapy and cardiovascular disease in postmenopausal women, are reviewed. Although conclusions concerning the specific hormones used in the specific populations studied can be offered from the completed trials, more broad conclusions concerning the use of hormone replacement therapy in the prevention of cardiovascular disease will have to await conduction and completion of other trials. PMID- 11772424 TI - Peroxisome proliferator-activated receptors. AB - An exciting and rapidly evolving area in vascular biology and atherosclerosis research over the past 3 years has been the establishment of peroxisome proliferator-activated receptor (PPAR) expression in the vascular and inflammatory cells, and the emerging picture of the roles these ligand-activated nuclear receptor/transcription factors might play in vascular biology and atherosclerosis. Such work is all the more compelling given the ongoing clinical use of PPAR activators in patients. Thiazolidinediones (PPAR-g agonists) are used as insulin sensitizers in diabetic patients known to be at extraordinarily high risk for cardiovascular disease, whereas fibrates (PPAR-a agonists) are used to treat dyslipidemia, particularly in the case of high triglycerides and low high density lipoprotein cholesterol. PMID- 11772425 TI - Inhibition of acyl coenzyme A-cholesterol acyltransferase: a possible treatment of atherosclerosis? AB - Our full understanding of atherosclerosis and our ability to prevent its sequellae are incomplete. As a result, further investigation of novel antiatherosclerotic mechanisms and agents continues. Acyl coenzyme A-cholesterol acyltransferase (ACAT) inhibition has been evaluated as a potential mechanism by which the current treatment arsenal may be expanded. ACAT is present in a variety of tissues and is responsible for catalyzing the conversion of free cholesterol to the more readily stored cholesteryl esters. Impressive lipid effects demonstrated in animals have not generally been demonstrated in human clinical trials. Partial ACAT inhibition with specific agents has resulted in lesion regression and decreased progression, whereas complete ACAT inhibition via genetic alterations has led to an exacerbation of cholesterol deposition in tissues in animal models. No ACAT inhibitor has yet been fully evaluated in human clinical trials for its impact on atherosclerotic disease progression. Several hurdles, such as sample size requirements needed to detect effect over background therapy and lack of sensitive surrogate efficacy markers, have served as a deterrent to the development of this class of investigational drug. However, with recent technologic advancements, more sensitive methods of measuring disease progression may be available. Human clinical trials are currently underway, with several agents reported in Phase II clinical trials. Within the next few years, results from these trials may determine whether or not ACAT inhibitors will be added to the list of treatment options for the prevention of atherosclerotic disease progression. PMID- 11772426 TI - Gut-acting drugs for lowering cholesterol. AB - Drugs that indirectly lower blood cholesterol through their actions in the gut have been used for many years. Their utility has been limited by poor tolerability, and hence, poor compliance. New resins are better tolerated and offer an advantage to older drugs. New strategies focusing on reducing serum cholesterol by acting on the gastrointestinal tract may hold even greater promise, combining the safety of nonsystemic agents with the acceptance of statins. PMID- 11772427 TI - Endostatin reduces vascularization, blood flow, and growth in a rat gliosarcoma. AB - Endostatin, the 20-kDa C-terminal fragment of collagen XVIII, has previously been shown to inhibit growth and induce regression of different experimental tumors in rodents. In this study, we show that recombinant murine and human endostatin, produced in 293 EBNA cells and yeast, respectively, inhibit ectotopic as well as orthotopic growing BT4Cn gliosarcomas in BD-IX rats. In rats in which s.c. gliomas were grown for a total of 29 days, systemic treatment with recombinant murine endostatin induced about 50% reduction of intratumoral blood flow and tumor size after only 10 days of therapy. In contrast, the blood flow to irrelevant organs was unaffected by endostatin, indicating its specificity of action. Tumors were not observed to increase in size or regrow after cessation of therapy. Furthermore, endostatin-treated rats with i.c. tumors had significantly longer survival time than did untreated controls. In the treated rats, endostatin therapy resulted in a reduced tumor blood vessel volume and an increased tumor cell density with an increased apoptotic index within a given tumor volume, as verified by flow cytometry and by staining with deoxynucleotidyltransferase mediated dUTP nick-end labeling. This work verifies the general anti-angiogenic and antitumor effects of endostatin and indicates that the protein may also be considered as a treatment strategy for malignant brain tumors. PMID- 11772428 TI - Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation. AB - Both increased cell proliferation and apoptosis play important roles in the malignant growth of glioblastomas. We have demonstrated recently that the differential expression of protein kinase C (PKC)-eta increases the proliferative capacity of glioblastoma cells in culture; however, specific functions for this novel PKC isozyme in the regulation of apoptosis in these tumors has not been defined. In the present study of several glioblastoma cell lines, we investigated the role of PKC-eta in preventing UV- and gamma-irradiation-induced apoptosis and in caspase-dependent signaling pathways that mediate cell death. Exposure to UV or gamma irradiation killed 80% to 100% of PKC-eta-deficient nonneoplastic human astrocytes and U-1242 MG cells, but had little effect on the PKC-eta-expressing U 251 MG and U-373 MG cells. PKC-eta appears to mediate resistance to irradiation specifically such that when PKC-eta was stably expressed in U-1242 MG cells, more than 80% of these cells developed resistance to irradiation-induced apoptosis. Reducing PKC-eta expression by transient and stable expression of antisense PKC eta in wild-type U-251 MG cells results in increased sensitivity to UV irradiation in a fashion similar to U-1242 MG cells and nonneoplastic astrocytes. Irradiation of PKC-eta-deficient glioblastoma cells resulted in the activation of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and a substantial increase in subdiploid DNA content that did not occur in PKC-eta expressing tumor cells. A specific inhibitor (Ac-DEVD-CHO) of caspase-3 blocked apoptosis in PKC-eta-deficient U-1242 MG cells. The data demonstrate that resistance to UV and gamma irradiation in glioblastoma cell lines is modified significantly by PKC-eta expression and that PKC-eta appears to block the apoptotic cascade at caspase-9 activation. PMID- 11772429 TI - A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas. AB - Although dexamethasone is very effective for controlling peritumoral cerebral edema, it is associated with distressing side effects that decrease the quality of life for many patients. One potential mechanism to explain the ability of dexamethasone to repair blood-brain barrier dysfunction is through the inhibition of cyclooxygenase-2 (COX-2). The purpose of this study was to determine in a rat brain tumor model whether SC-236, a selective COX-2 inhibitor, is as effective as dexamethasone. Twenty-nine adult male Fischer 344 rats were implanted with intracerebral 9L gliosarcomas and divided into 3 treatment groups. One group (n = 9) served as controls, another (n = 9) was treated with dexamethasone (3 mg/kg p.o. daily), and a third group (n = 11) received SC-236 (3 mg/kg p.o. daily). A survival study was performed. The median survival in the control group was 16 days, compared with 23 days for the dexamethasone group and 23 days for the COX-2 inhibitor group. Kaplan-Meier analysis on pairwise group comparisons showed improved survival that was statistically significant for each treatment group compared with the control group (log-rank test P = 0.009 for dexamethasone to control and P = 0.005 for COX-2 to control), and no significant difference in survival for the COX-2 compared with dexamethasone (log-rank test P = 0.2). These results suggest that a selective COX-2 inhibitor appears to be as effective as dexamethasone in prolonging survival in a rat brain tumor model. PMID- 11772430 TI - Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy. AB - Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future. PMID- 11772431 TI - A phase II study of extended low-dose temozolomide in recurrent malignant gliomas. AB - Temozolomide is an effective agent in the treatment of recurrent malignant gliomas. The standard dosage is 150-200 mg/m2 per day for 5 days in a 28-day cycle. A prior phase I study established a chronic daily temozolomide dose that significantly increased the total dose administered and suggested a superior response rate. In a prospective phase II trial, we treated 35 patients with recurrent malignant gliomas with temozolomide 75 mg/m2 per day for 42 consecutive days in a 70-day cycle. Median age was 55 years (range, 27-73 years) and median Karnofsky performance score was 70 (range, 60-90). Twenty-eight (79%) patients had glioblastoma multiforme, 3 (9%) anaplastic astrocytoma, 2 (6%) anaplastic oligodendroglioma, and 2 (6%) anaplastic oligoastrocytoma. All but one had prior radiotherapy, and 27 had prior chemotherapy. There were 2 partial (anaplastic astrocytoma) and 3 minor (glioblastoma multiforme) radiographic responses; 17 patients had progressive disease at the end of the first cycle. In 55 cycles of temozolomide, there were 8 episodes of asymptomatic drug-related grade 3 toxicity: 6 lymphopenia, 1 neutropenia, and 1 thrombocytopenia. Median progression-free survival and overall survival were 2.5 and 8.7 months (2.3 and 7.7 months in glioblastoma multiforme patients). At 6 months, progression-free survival and overall survival rates were 27% and 67% (19% and 60% in glioblastoma multiforme). Quality of life scores did not change significantly during treatment. We conclude that the extended low-dose schedule of temozolomide is well tolerated in heavily pre-treated patients; however, our results do not support an improved rate of response or survival. PMID- 11772432 TI - Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: case study and review of the literature. AB - Parathyroid carcinoma is an uncommon malignancy. Of the fewer than 400 cases reported, most have been cases of producing parathyroid carcinoma with accompanying hypercalcemia. Only 13 patients with nonproducing parathyroid carcinoma have been described. Nine of these 13 patients had metastatic disease. We report a patient with i.c. metastasis. Distal metastases of producing parathyroid carcinoma are treated surgically to prolong survival and prevent complications of hyperparathyroidism and hypercalcemia. One half of the patients with producing parathyroid carcinoma die within 5 years, mostly because of the complications of hypercalcemia. Nonproducing parathyroid carcinoma compares unfavorably with producing parathyroid carcinoma in terms of tumor progression and prognosis. Few data on choice of therapy in nonproducing parathyroid carcinoma are available. We treated our patient with a combination of radiotherapy and chemotherapy. Treatment was followed by an unexpectedly prolonged survival of 31 months after diagnosis of metastatic disease. PMID- 11772433 TI - Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG. AB - We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred. PMID- 11772434 TI - A simple method to measure stride length as an index of nigrostriatal dysfunction in mice. AB - Reduced stride length characterizes Parkinsonian gait. We aimed to demonstrate that it could be measured simply and reliably in mice by pawprints and used as an index of basal ganglia dysfunction. In C57BL/6 mice, stride length measurements proved to be consistent across measurements and experimenters. It was slightly lower in the hindlimbs and was correlated to femur size and animal velocity. Dopamine depletion by reserpine and striatal dopamine receptor blockade by haloperidol resulted in reduced mean stride length in four limbs. Significant forelimb/hindlimb difference was also observed both in mice with 3-nitropropionic acid (3-NP) induced striatal lesions and in those with MPTP-induced nigral cell loss. Reduction of hindlimb stride length was correlated significantly with the magnitude of cell loss, either in the substantia nigra or in the lateral mid striatum. Stride length is, therefore, a simple method to obtain an index of motor disorders due to basal ganglia dysfunction in mice. PMID- 11772435 TI - Quantification of a single exploratory trip reveals hippocampal formation mediated dead reckoning. AB - A rat's proclivity to explore a novel environment presents a behaviorally rich paradigm to investigate the role of the hippocampus in spatial navigation. Here we describe a novel technique of behavioral analysis that is derived from a single exploratory trip. An exploratory trip was defined as a rat's departure from the home base that ended when the rat returned to the home base. The behavior observed on a single exploratory trip by a control animal is highly organized into outward and homeward segments. An outward segment is characterized by a slow circuitous progression from the home base marked by several stops. A homeward segment is characterized by a rapid direct return to the home base. The velocity attribute of the exploratory trip was quantified by estimating the point of inflection associated with the trip's cumulative moment-to-moment velocity distribution. The heading direction and variance of the homeward trip segment was analyzed with circular statistics. A comparison of the exploratory behavior of control animals and animals with damage to the fimbria-fornix indicated that the velocity and heading direction of the homeward portion of the trip depends upon the hippocampal formation. While control and fimbria-fornix rats had similar outward segments, the return paths of the fimbria-fornix rats were significantly slower, more circuitous, and more variable compared with that of the control rats. This result was also independent of testing in light or dark conditions. The lack of dependence on allothetic cues suggests that rats employ dead reckoning navigational strategies to initiate the homeward portion of exploratory movements. Methods to quantify exploratory behavior in terms of velocity and angular components provide an assessment of control behavior and the assessment of the behavior of rats with hippocampal formation damage that is easy to implement. PMID- 11772436 TI - High resolution scanning and three-dimensional reconstruction of cellular events in large objects during brain development. AB - Detailed knowledge of the spatial and temporal interactions of distinct cellular events and of the genes involved in their regulation is a precondition for the understanding of morphogenetic and pathogenetic processes. Here, how patterns of cellular events in large objects can be visualized with the help of the image acquisition system 'Huge Image' is demonstrated. Huge images are composed of a multitude of small images scanned with the highest light microscopical resolution. The system is equipped with a programmable autofocus device and permits precise and rapid cytological diagnosis. A vector-based three-dimensional (3-D) reconstruction method which, in future projects, will be combined with 'Huge Image', is applied to visualize dynamic interactions between macrophages and the occurrence of apoptotic neuroepithelial cells in the early developing forebrain of Tupaia belangeri (Scandentia). Proportionally correct meshwire surfaces of small and large objects are generated independently of each other. The combined reconstruction of cellular events and large embryonic surfaces can be carried out from only subsets of histological serial sections, and, compared with volume-based systems, with a much lower need for memory. The practicability of our approach is compared with recent other methods used to demonstrate apoptotic patterns. PMID- 11772437 TI - Programmable microchip monitoring of post-stroke pyrexia: effects of aspirin and paracetamol on temperature and infarct size in the rat. AB - BACKGROUND: Recent studies have demonstrated spontaneous and prolonged hyperthermia following stroke in both humans and rodents. However, a full characterization of these pyretic changes and the effects of anti-pyretic drugs on outcome is not available. METHODS: The aims of this study were to monitor conscious body temperature (n=10 per group) using programmable microchips for up to 24 h in rats following either permanent (p) or 90 min transient (t) middle cerebral artery occlusion (MCAO) or sham surgery, and to evaluate the relationship to hypothalamic damage. Also, the effects of anti-pyretic drug therapy on body temperature and infarct volume were evaluated in animals treated with vehicle, optimal doses of either aspirin or paracetamol (250 mg/kg i.p.) following pMCAO (n=10 per group). RESULTS: At 1 h, body temperature significantly (P<0.01) increased to 38.6+/-0.2 degrees C following tMCAO and 38.9+/-0.1 degrees C following pMCAO compared with sham-operated animals (37.1+/-0.1 degrees C). Sustained hyperthermia (> or =38.1 degrees C) was observed for up to 24 h following pMCAO but approached baseline within 30 min (37.6+/-0.2 degrees C) following tMCAO with reperfusion. The post-stroke pyrexia was related to the degree of ischemia where hypothalamic damage was observed in (80%) of the animals undergoing pMCAO and (0%) in the tMCAO group (P<0.05). Treatment with paracetamol (250 mg/kg i.p.) significantly attenuated (P<0.05) but did not normalize core body temperature up to 2 h (38.2+/-0.4 degrees C) compared with vehicle treated animals (39.3+/-0.1 degrees C). Aspirin had no effect on temperature under these conditions. Hypothalamic damage and lesion volume were not different between animals treated with paracetamol (253.3+/-8.5 mm(3)), aspirin (264.0+/-11.6 mm(3)) or vehicle (274.4+/-8.2 mm(3)). CONCLUSIONS: This study is the first to demonstrate the utility of programmable microchips to monitor serial changes in post-stroke hyperthermia. The sustained post-stroke pyrexia and negative effects of antipyretic treatment may be attributed to the extensive hypothalamic injury suggesting that better pharmacologic approaches to reduce body temperature should be identified and evaluated for brain protection in severe experimental stroke. PMID- 11772438 TI - A method to induce swapped binaural hearing. AB - This paper describes the application of a small hearing aid that precisely fits into a subject's ear canal (complete-in-canal, or CIC). The bandwidth of the device is about 7 kHz. The system allows for selective manipulation of the different acoustic cues used for sound localization. The potential of the system is illustrated by robustly interchanging the input of the left and right ear, and consequently changing the sign of the binaural difference cues (both interaural phase and intensity) that are used for horizontal sound localization. As a result, left-right perception is reversed, while high-frequency pinna cues are sufficiently preserved to maintain up-down localization. As the hearing condition is well-defined, the auditory system could in principle remap these cues into a new representation of sound azimuth by relating the modified cues to veridical sound locations. The hearing aids were applied in four human subjects. Swapped binaural hearing was tested in two of the subjects. Swapped localization experiments for an extended period indicated stable performance of both subjects. Interestingly, an adaptive response to the reversed interaural cues was not observed. The current system may prove useful for psychophysical studies that concern the independent processing of sound localization cues, as well as in long term developmental and plasticity studies with animals. PMID- 11772439 TI - A template subtraction method for stimulus artifact removal in high-frequency deep brain stimulation. AB - Deep brain stimulation (DBS) is a neurosurgical technique that has been widely applied for the treatment of tremor or motor symptoms associated with advanced Parkinson's disease. Large stimulus artifacts, however, have hampered investigations of physiological mechanisms underlying DBS effects using extracellular recording techniques. We have developed an off-line procedure for removing stimulus artifacts from recorded neuronal signals (monopolar) and applied this method of artifact subtraction to DBS studies using extracellular recording techniques in a nonhuman primate. The procedure consists of developing a template of the artifact by averaging the artifact signals triggered by its onset. The template is then subtracted from the individual triggered signals. The experimental results indicate that this method is highly effective in removing the majority of the stimulus artifact, while leaving recorded neuronal activity intact. In fact, removal of stimulation artifact using this technique has revealed a short-latency neuronal response to stimulation that was previously obscured by the stimulus artifact. Thus, this technique may not only improve the quality of electrophysiological studies employing DBS techniques, but may also help to elucidate neuronal mechanisms underlying the effect of DBS. PMID- 11772440 TI - Method for assessing directional characteristics of non-uniformly sampled neural activity. AB - We present a new analytical method for characterizing the directional tuning of neural data. The method is based on computing parameters associated with the geometric properties of solids, and provides an estimate of preferred direction in the context of non-uniform sampling of directions. Unlike optimization methods based on fitting tuning functions, the plate method is computationally fast, and does not require the assumption of an underlying tuning function (e.g. cosine or von Mises functions). In addition to estimating the preferred direction of a dataset, the plate method provides other parameters to fully characterize the directional properties of neural data. The method is presented in the context of a two-dimensional coordinate system but may in principle be extended to higher dimensional spaces as well. PMID- 11772441 TI - A new method for the investigation of capillary structure. AB - Numerous physiological conditions as well as behavioral conditions have been shown to influence central nervous system vascular structure. Many of the methods used to investigate these structural alterations take advantage of the visibility of viscous substances (e.g. India ink in gelatin) perfused into the vasculature. The high viscosity of the solution, however, can cause incomplete vessel perfusion. The aim of the present study was to test whether or not capillaries seen in tissue perfused with fixative, embedded in celloidin and stained with Methylene Blue-Azure II (n=6) could be a useful alternative for the investigation of brain vascular structure. The method was compared to tissue from six rats perfused with India ink in gelatin and stained with cresyl violet. Qualitatively, vessels in the standard perfused tissue embedded in celloidin yielded clear vessels with stained pericytes. The two methods did not differ in branch point to cell ratio, length of individual capillaries, vessel length per mm(3), and capillary tortuosity. The capillary diameter was greater in the celloidin embedded tissue than in the India ink perfused tissue. Measuring the diameter between vessel walls appears to provide a more accurate measure than the widest distance between India ink pigments. Quantitative comparisons suggest that perfusion with standard fixative followed by embedding in celloidin provides vascular quantification comparable to that from India ink perfused tissue. The present method has several advantages, which include visualization of pericytes, increased probability of complete perfusion, clear view of cells that might otherwise be obscured by opaque vessels, and the possibility of using the alternate cerebral hemisphere for investigation of vascular ultrastructure. PMID- 11772442 TI - Achieving optimal expression for single channel recording: a plasmid ratio approach to the expression of alpha 1 glycine receptors in HEK293 cells. AB - In single-channel recording, optimal yield of kinetic data is achieved if simultaneous activations of more than one channel are few. When recordings are obtained from recombinant channels, it is therefore important to control the level of expression of the channel at the cell surface, while maintaining a high efficiency of transfection. In the present study, we optimised transfection protocols for single-channel recording from recombinant rat alpha 1 glycine receptors expressed in HEK293 cells. High transfection efficiency was achieved with lipofection (up to 70%). Lipofected cells however did not lend themselves to excised patch recording because of seal instability, especially obvious at hyperpolarised holding potentials. High quality excised patch recordings were reliably achieved with the calcium phosphate-DNA coprecipitation method, with transfection efficiencies around 40%. We achieved good control of the level of receptor expression by a plasmid ratio approach which kept the total amount of plasmid transfected constant while varying the ratio between alpha 1-containing plasmid and empty plasmid vector. The maximum amplitude of glycine-evoked currents was reliably dependent on the percentage of alpha 1-containing plasmid. Optimum results for steady-state single channel experiments at low glycine concentrations were obtained with 5% of alpha 1 plasmid DNA in the transfection mix. PMID- 11772443 TI - Genotyping methods to detect a unique neuroprotective factor (Wld(s)) for axons. AB - The slow Wallerian degeneration mouse, C57BL/Wld(s), carries a dominant mutation that delays Wallerian degeneration in the distal stump of an injured axon. The protective gene has been identified and also found to protect axons from the neurotoxin vincristine. Therefore, it is important to determine whether it has a widespread application to protect axons in neurological disease. In principle, this can be done by crossing Wld(s) to neurological mutant mice, but first a method is needed to track the inheritance of the neuroprotective Wld(s) allele. Due to the complex nature of the mutation, there is no simple method to distinguish Wld(s) homozygotes, heterozygotes and wild-type mice. Therefore, we report a genotyping method for Wld(s) based upon pulsed field gel electrophoresis (PFGE) and compare it with the alternatives of PCR and Southern blotting. The effect of the Wld(s) mutation on axon degeneration in diverse inherited pathologies, and the consequence for symptoms, can now be investigated. PMID- 11772444 TI - Release of recombinant human interleukin-2 from dextran-based hydrogels. AB - In this study, the release of recombinant human interleukin-2 (rhIL-2) from methacrylated dextran (dex-MA) and (lactate-)hydroxyethyl methacrylated dextran (dex-(lactate-)HEMA) hydrogels with varying crosslink density was investigated. Hydrogels derived from dex-MA are stable under physiological conditions (pH 7 and 37 degrees C), whereas dex-HEMA and dex-lactate-HEMA hydrogels degrade due to the presence of hydrolytically sensitive esters in the crosslinks of the gels. The protein release profiles both the non-degradable and degradable dextran-based hydrogels showed that with increasing crosslink density of the gel, the release of rhIL-2 decreases. From dex-MA hydrogels with an initial water content above 70%, the rhIL-2 release followed Fickian diffusion, whereas from gels with an initial water content of 70% or lower the protein was fully entrapped in the hydrogel meshes. In contrast with non-degradable dex-MA hydrogels, degradable dex lactate-HEMA gels with comparable network characteristics (degree of methacrylate substitution and initial water content) showed an almost zero-order, degradation controlled release of rhIL-2 in a time period of 5-15 days. This paper demonstrates that the release of rhIL-2 from non-degradable dex-MA and degradable dex-lactate-HEMA gels can be modulated by the crosslink density and/or the degradation characteristics of the hydrogel. Importantly, rhIL-2 was mainly released as monomer from the hydrogels and with good retention of its biological activity. PMID- 11772445 TI - Design of biodegradable particles for protein delivery. AB - Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate protein carriers in order to overcome mucosal barriers. We have attempted to combine both issues through the conception of new biodegradable polymer nanoparticles: (i) poly(ethylene glycol) (PEG)-coated poly(lactic acid) (PLA) nanoparticles, chitosan (CS)-coated poly(lactic acid-glycolic acid (PLGA) nanoparticles and chitosan (CS) nanoparticles. These nanoparticles have been tested for their ability to load proteins, to deliver them in an active form, and to transport them across the nasal and intestinal mucosae. Additionally, the stability of some of these nanoparticles in simulated physiological fluids has been studied. Results showed that the PEG coating improves the stability of PLA nanoparticles in the gastrointestinal fluids and helps the transport of the encapsulated protein, tetanus toxoid, across the intestinal and nasal mucosae. Furthermore, intranasal administration of these nanoparticles provided high and long-lasting immune responses. On the other hand, the coating of PLGA nanoparticles with the mucoadhesive polymer CS improved the stability of the particles in the presence of lysozyme and enhanced the nasal transport of the encapsulated tetanus toxoid. Finally, nanoparticles made solely of CS were also stable upon incubation with lysozyme. Moreover, these particles were very efficient in improving the nasal absorption of insulin as well as the local and systemic immune responses to tetanus toxoid, following intranasal administration. In summary, these results show that a rational modification in the composition and structure of the nanoparticles, using safe materials, increases the prospects of their usefulness for mucosal protein delivery and transport. PMID- 11772446 TI - Transforming growth factor beta-3 crystals as reservoirs for slow release of active TGF-beta3. AB - Transforming growth factor betas (TGF-betas) play critical roles in many diseased states and injury repair processes. Exogenous delivery of TGF-beta may thus have therapeutic applications. Here, crystals of TGF-beta3 (TGF-beta3) are being evaluated as protected reservoirs for sustained local release. A sensitive Mv1Lu cell growth inhibition assay established that in vitro, active TGF-beta3 can be delivered from physically stable crystals. Non-sink release experiments revealed that crystal solubility at pH 7.4 was higher in cell culture medium (2.7+/-0.1 microg/ml) than in saline buffers (approximately 1-1.5 microg/ml, P<0.05). Addition of serum induced a five-fold delay in equilibration of soluble-crystal TGF-beta3. Semi-sink experiments cumulated in higher TGF-beta3 release than under non-sink conditions; the observed steady states correlated with crystal solubility and the frequency of buffer exchange. Release of TGF-beta3 from crystals was also strongly dependent on solubility changes as affected by pH. At neutral pH the solubilities were the lowest, and increased with both higher and lower pH. The results indicate that TGF-beta3 crystals may have promising features for local pH-triggered sustained-release applications. PMID- 11772447 TI - Regulation of protein and vesicle trafficking at the apical membrane of epithelial cells. AB - The characterization of endocytotic and post-endocytotic trafficking pathways at the apical membrane of epithelial cells presents a potential avenue for the identification of targets to modulate the initial stages of absorption and transepithelial transport of macromolecules. In addition, it is becoming increasingly clear that the activity of a number of apical membrane transporters is acutely regulated by vesicular trafficking. The gastric HCl-secreting parietal (oxyntic) cell is a model system to characterize an apical membrane vesicular trafficking pathway and its relationship to the regulation of the function of the gastric proton pump. The subapical tubulovesicular compartment of the parietal cell is highly enriched in the H,K-ATPase and is a key endosomal-like system in the apical membrane recycling pathway. In the process of cataloging the proteins that interact with the H,K-ATPase and tubulovesicles, we have identified novel components that may regulate protein sorting through this compartment and candidate linker proteins between the vesicular trafficking machinery and the cytoskeleton. One protein associated with H,K-ATPase-rich tubulovesicles is the nonreceptor tyrosine kinase c-src, identified by a screen for dynamin-binding proteins. The tyrosine kinase is active, as it can tyrosine-phosphorylate tubulovesicular proteins in vitro. One of the tyrosine-phosphorylated proteins of M(r) 100 kDa may be the H,K-ATPase itself, or a protein in a complex with the H,K ATPase that is stable to dissociation by nonionic detergents. By virtue of its association with tubulovesicular membranes, c-src may regulate the trafficking and/or activity of the H,K-ATPase. A second protein identified by a screen for dynamin-binding proteins is the protein lasp-1. Lasp-1, through its modular protein structure, may bind to dynamin and to the actin cytoskeleton, thus linking the vesicular trafficking machinery with the cytoskeleton. These two examples illustrate the utility of the parietal cell in the biochemical characterization of components potentially involved in the regulation of apical membrane trafficking pathways. PMID- 11772448 TI - Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. AB - Cumulative studies have revealed the importance of transporters in drug disposition in the body. Recently, organic anion transporters such as organic anion transporting polypeptides (OATPs), organic anion transporters (OATs) and multidrug resistance associated proteins (MRPs) have been identified. Their broad substrate specificity as well as the multiplicity of transporter gene products make these transporters suitable detoxification systems in the body. OATPs and OATs are responsible for the hepatic and renal uptake of organic anions, respectively, while MRP2 is a major transporter involved in the biliary excretion of organic anions. OATPs and MRP2 are involved in the hepatobiliary transport of pravastatin and temocaprilat. These are good examples of hepatobiliary transport maximizing their pharmacological effects, but minimizing their side-effects. Taking into consideration tissue-selective expression and substrate specificity, transporters are useful for delivering small molecules to target tissues. MRPs are also suggested to be involved in the barrier function in the small intestine, blood-brain barrier and blood-cerebrospinal fluid barriers by extruding their ligands into the luminal side. In this manuscript, we have summarized recent studies by others and ourselves on the role of these transporters in the tissue selective distribution and elimination of drugs. PMID- 11772449 TI - Modulation of murine liver macrophage clearance of liposomes by diethylstilbestrol. The effect of vesicle surface charge and a role for the complement receptor Mac-1 (CD11b/CD18) of newly recruited macrophages in liposome recognition. AB - We have studied the blood clearance and reticuloendothelial organ distribution of intravenously injected neutral (egg phosphatidylcholine, egg PC/cholesterol, mol ratio 7:2), anionic (egg PC/cholesterol/dicetylphosphate, mol ratio 7:2:1), and cationic (egg PC/cholesterol/stearylamine, mol ratio 7:2:1) liposomes of approximately the same size distribution in mice 3 days after treatment with the synthetic oestrogen diethylstilbestrol (DES). Male mice administered DES intraperitoneally at a dose of 1 mg per mouse (body weight 22-25 g) manifested an increase in the vascular clearance rate of liposomes irrespective of the initial vesicle surface charge. The enhancement in the vascular clearance of liposomes in DES-treated animals was associated with a concomitant increase in liver weight as well as hepatic phagocytosis. However, DES treatment significantly enhanced the hepatic sequestration (on the basis of % of injected dose of liposomes per g of liver tissue) of positively charged liposomes when compared to both neutral and negatively charged vesicles of similar size distribution. This observation was also confirmed by the 'hepatic-blockade' experiments where blockade was induced by prior intravenous injection of liposomes of the same size distribution and charge to that of test vesicles. The in vitro cell suspension studies suggested that the enhanced liposome uptake (irrespective of the initial vesicle surface charge) by Kupffer cells of DES-treated mice was independent of changes in the blood opsonization processes. Furthermore, in vitro studies also showed the operation of multiple mechanisms and involvement of different populations of liver macrophages (resident and recruited cells) in liposome recognition following DES treatment. For example, in DES-treated animals, the newly recruited liver macrophages were found to play a major role in the clearance of stearylamine incorporated liposomes via complement receptors (Mac-1). The resident Kupffer cells seem to recognize cationic vesicles via other receptors as the expression of Mac-1 is virtually absent in these cells. On the other hand, complement receptors seem to play a minor role in the uptake of anionic DCP vesicles by hepatic macrophages of DES-treated mice. DES appears to offer a new approach in dissecting the mechanisms of liposome-macrophage interaction. PMID- 11772450 TI - ATTEMPTS: a heparin/protamine-based delivery system for enzyme drugs. AB - A prodrug delivery system termed "Antibody Targeted, Triggered, Electrically Modified Prodrug-Type Strategy (ATTEMPTS)" has been developed to permit the antibody-directed administration of inactive enzyme drug including tissue-type plasminogen activator (tPA), and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin-antifibrin complex via ionic interaction, and the active tPA can subsequently be released by the addition of protamine, a competitive heparin inhibitor. Anti-fibrin IgG was conjugated to heparin via an end-point attachment to form the heparin-antifibrin complex which provides the targeting efficiency of the final heparin/mtPA complex. Cation modification was performed by either chemical conjugation by linking (Arg)7Cys to tPA with N-succinimidy-3-(2 pyridyldithio) propionate or by recombinant DNA methods. Results show that the modification process did not significantly alter the specific activity of tPA with regard to plasminogen activation, fibrin-binding ability, and response toward fibrinogen. The complexes of both modified tPA-heparin did not yield any intrinsic catalytic activity owing to the blockage of the active site of tPA by the attached heparin. On the other hand, heparin-induced inhibition of modified tPA activity was reversed by adding protamine, which is similar to that of a prodrug delivery system. These results suggest that heparin/protamine-based enzyme delivery systems may be a useful tool to improve current enzyme therapeutic status, as well as thrombolytic therapy, by both regulating the release of active enzyme and aborting the associated systemic toxic effect. Currently, modification of enzyme drugs has been optimized by recombinant DNA technology assisted by computer simulation. In addition, the original strategy has been revised to obtain enhanced therapeutic efficacy. PMID- 11772451 TI - Clinical aspects of drug delivery to tumors. AB - This report describes our experience on enhancement of drug delivery to solid tumors. Results of our preclinical and clinical studies including a randomized prospective phase III trial have validated the concept that enhanced drug delivery can significantly improve the treatment efficacy of intravesical mitomycin C therapy of superficial bladder cancer. The report further describes the roles of interstitial space, drug removal by capillaries, tissue structure and tissue composition on drug distribution. In general, drug distribution favors interstitial space and vasculature, with little penetration in muscles. The transport of highly protein-bound drugs such as paclitaxel and doxorubicin in a solid tumor is retarded by a high tumor cell density and enhanced by drug-induced apoptosis. Results of in vitro studies using solid tumor histocultures and in vivo studies using tumor-bearing animals demonstrate that the delivery of highly protein-bound drugs to tumor can be enhanced using a pretreatment that induces apoptosis and reduces cell density, and by using treatment schedules designed to take advantage of these drug-induced changes in tumor tissue composition. PMID- 11772452 TI - Acquired and specific immunological mechanisms co-responsible for efficacy of polymer-bound drugs. AB - We present data providing new evidence that poly[N-(2 hydroxypropyl)methacrylamide] (PHPMA)-bound drugs, unlike free drugs, have both cytostatic and immunomobilizing activity (CIA). Immediately after injection, due to the high level of the drug, the main activity of the polymeric conjugate is cytotoxic and cytostatic. Later on, long-term circulating PHPMA-bound drug, at concentrations lower than its minimal inhibitory levels, mobilizes the defense mechanisms of the host. Cytotoxic and cytostatic effects of drug-PHPMA were repeatedly confirmed. The following data support the concept of the immunomobilizing activity of the N-(2-hydroxypropyl)methacrylamide (HPMA) conjugates: (a) pre-treatment with free drugs (doxorubicin, cyclosporin A) accelerates the appearance of EL4 mouse T-cell lymphoma while a similar pre treatment with doxorubicin-PHPMA induces limited but definitive mobilization of the host's defense mechanisms; (b) mice cured of EL4 mouse T-cell lymphoma, BCL1 mouse B-cell leukemia and 38C13 mouse B-cell lymphoma by injection of doxorubicin PHPMA conjugate targeted with monoclonal antibodies (anti-Thy 1.2 for EL4, anti B1 for BCL1 and anti-CD71 for 38C13) and re-transplanted with a lethal dose of the same cancer cells survive without any treatment considerably longer than control mice; (c) increased NK activity and anti-cancer antibody was detected only in animals treated with doxorubicin-PHPMA conjugate; and (d) considerably increased NK and LAK activity was seen in a human patient treated for generalized breast carcinoma with doxorubicin-PHPMA-IgG. PMID- 11772453 TI - Designing peptide-based scaffolds as drug delivery vehicles. AB - Methods for delivering drugs into cells remain an important part of the process of designing drugs. One promising approach is the concept of loligomers, synthetic peptides composed of a branched polylysine core harboring identical arms. Loligomers are typically synthesized with eight arms, each carrying peptide signals guiding their import and localization into cells. The most important advantage of loligomers is the multivalent presentation of targeting signals resulting from a tentacular arrangement. Multivalency increases the efficiency of import and intracellular routing signals as compared to similar linear peptides. Secondly, it reduces and delays the impact of peptide degradation in terms of cellular processing and compartmentalization. The vectorial delivery of nucleus directed loligomers into cells has recently been confirmed by microscopy and flow cytometry studies. Practical uses of loligomers as intracellular vehicles include the import of plasmid DNA into cells, the conjugation of chemical groups, such as photosensitizers for use in photodynamic therapy, and the incorporation of cytotoxic T-lymphocyte (CTL) epitopes with a view to creating synthetic vaccines. Branched peptides such as loligomers represent simple and versatile molecular vehicles with potential applications in a wide variety of drug design approaches. PMID- 11772454 TI - Device-directed therapeutic drug delivery systems. AB - To increase the therapeutic effectiveness of device-directed drug delivery systems for diseased cardiovascular tissues and cancerous tissues, new devices and new functional biomaterials were devised to meet the requirements as listed below: drug-infusible balloon catheter, drug-releasable and covered stents, and in situ hydrogelation on and in cancerous tissues. New therapeutic strategies based on these devices were discussed. PMID- 11772455 TI - Development of poly(ortho esters) and their application for bovine serum albumin and bupivacaine delivery. AB - The preparation of drug delivery devices using solventless fabrication procedures is of significant interest and two such procedures are described. In one such procedure, powdered polymer and micronized protein are intimately mixed and then extruded into 1 mm strands that are cut to the desired length. The polymers used were specifically designed to allow extrusion at temperatures where proteins maintain activity in the dry state. In vitro erosion and BSA release show that BSA release and polymer erosion occur concomitantly indicating an erosion controlled process. There is a lag-time, but that can be eliminated by the addition to the mixture prior to extrusion small amounts of poly(ethylene glycol) or its methoxy derivatives. The lag-time could also be eliminated by using an AB block copolymer where A is poly(ortho ester) and B is poly(ethylene glycol). Another means of using solventless fabrication methods is to use a semi-solid material into which drugs can be mixed at room temperature and the semi-solid injected. Data on BSA and bupivacaine release are presented. PMID- 11772456 TI - A synthetic polymer matrix for the delayed or pulsatile release of water-soluble peptides. AB - The design of a polymeric peptide release system with a controlled delay time and a burst-free pre-release phase is described. In general, the system consists of a blend of a tyrosine-derived polyarylate and a fast-degrading copolymer of lactic and glycolic acid (PLGA). Due to the peptide-like structure of the polyarylate backbone, peptide-polymer interactions prevented the release of peptide from neat polyarylate films. The addition of PLGA acts as a 'delayed' excipient: as PLGA degrades, it generates acidic degradation products that cause a drop in the internal pH of the polyarylate matrix. This drop in pH weakens the peptide polymer interactions and causes the release of peptide to commence. The initial molecular weight of PLGA can be used to control the length of time before degradation occurs. Consequently, this parameter can also be used to control the duration of the delay period prior to peptide release. As a specific model system, blends of poly(DTH adipate) with three different copolymers of lactic and glycolic acid were prepared and used for the delayed release of Integrilin, a synthetic water-soluble heptapeptide (clinically used in antithrombic injections) that acts as a highly potent glycoprotein IIb/IIIa antagonist. Blends composed of a 1:1 weight ratio of poly(DTH adipate) and PLGA and containing Integrilin (15%, w/w) were prepared. In vitro release studies were conducted in phosphate buffered solution at 37 degrees C and the release of Integrilin was followed by HPLC. As the initial molecular weight of PLGA varied from 12000 to 62000, the duration of the delay period prior to release increased from 5 to 28 days. PMID- 11772457 TI - Process design for efficient and controlled drug incorporation into polymeric micelle carrier systems. AB - For the efficient and well-controlled incorporation of the anti cancer drug adriamycin (ADR) into the inner core of a thermo-responsive polymeric micelle carrier system, we have analyzed and optimized the incorporation procedure in this paper. A dialysis method was used for preparing the micelle solution and ADR incorporation simultaneously. Quantities of ADR and triethylamine (TEA) were varied and the effects of their quantities were analyzed. Solvent composition at the starting time of dialysis was also varied. The initial dialysis condition, solvent with 40% water, brought about the largest amount and yield of ADR incorporation. With the initial 40% water content, it was considered that the block polymers formed a micelle-like association with a swollen hydrophobic core. This swollen core may be suitable for a large amount of ADR incorporation, since this core, swollen by an organic solvent-water mixture, is expected to show a liquid-state character to allow ADR molecules entry into the cores. By starting the dialysis procedure at this 40% water content, this swollen core suitable for the ADR incorporation is considered to be maintained for a much longer period than a case starting with a polymer-ADR solution in a solvent with a water content of less than 40%, and, therefore, ADR is expected to be incorporated efficiently. Preparation temperature of 20-25 degrees C was found to provide the most effective ADR incorporation in this thermo-responsive polymeric micelle system. These results indicate that the efficient incorporation of ADR can be achieved in consideration of the dynamic micelle formation and drug incorporation processes. PMID- 11772458 TI - Design of novel bioconjugates for targeted drug delivery. AB - This paper summarizes recent work on the design and development of targeted polymeric bioconjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. Polymerizable antibody Fab' fragment (MA-Fab') has been developed and used in the preparation of targeted HPMA copolymer-mesochlorin e6 conjugates for the treatment of human ovarian carcinomas. The reactivity of the MA-Fab' in copolymerization with HPMA depended on the length of the spacer between the monomer double bond and the antibody Fab' fragment. The biological activity of the antibody Fab' fragment was maintained after incorporation into the HPMA copolymer. Novel aromatic azo spacers were designed and incorporated into HPMA copolymer-drug (cyclosporin A, 9-aminocamptothecin) conjugates for the colon specific drug delivery and for the treatment of colon diseases. The colon specific drug release from the conjugates was controlled by the structures of both drug and spacers. Lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), were conjugated to the colon-specific polymer drug conjugates to enhance specific adhesion onto colon tissues. PMID- 11772459 TI - Design of segmented poly(ether ester) materials and structures for the tissue engineering of bone. AB - In this study, PEOT/PBT segmented copolymers of different compositions have been evaluated as possible scaffold materials for the tissue engineering of bone. By changing the composition of PEOT/PBT copolymers, very different mechanical and swelling behaviors are observed. Tensile strengths vary from 8 to 23 MPa and elongations at break from 500 to 1300%. Water-uptake ranges from 4 up to as high as 210%. The in vitro degradation of PEOT/PBT copolymers occurs both by hydrolysis and oxidation. In both cases degradation is more rapid for copolymers with high PEO content. PEOT/PBT scaffolds with varying porosities and pore sizes have been prepared by molding and freeze-drying techniques in combination with particulate-leaching. The most hydrophilic PEOT/PBT copolymers did not sustain goat bone marrow cell adhesion and growth. However, surface modification by gas plasma treatment showed a very much improved polymer-cell interaction for all PEOT/PBT copolymer compositions. Their mechanical properties, degradability and ability to sustain bone marrow cell growth make PEOT/PBT copolymers excellent materials for bone tissue engineering. PMID- 11772460 TI - Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. AB - For the purpose of obtaining high bone forming efficacy, development of chitosan was attempted as a tool useful as a scaffolding device. Porous chitosan matrices, chitosan-poly(L-lactide) (PLLA) composite matrices and chitosan coated on PLLA matrices were dealt with in this research. Porous chitosan matrix was fabricated by freeze-drying and cross-linking aqueous chitosan solution. Porous chitosan matrix combined with ceramics and constituents of extracellular matrices were prepared and examined for their bone regenerative potential. Composite porous matrix of chitosan-PLLA was prepared by mixing polylactide with chitosan and freeze-drying. All chitosan based devices demonstrated improved bone forming capacity by increasing mechanical stability and biocompatibility. Release of platelet-derived growth factor-BB (PDGF-BB) from these matrices exerted significant osteoinductive effect in addition to the high osteoconducting capacity of the porous chitosan matrices. The hydrophobic surface of PLLA matrices was modified by chitosan to enhance cell affinity and wettability. The chitosan coated PLLA matrix induced increased osteoblast attachment as compared with intact PLLA surface. Overall results in this study demonstrated the usefulness of chitosan as drug releasing scaffolds and as modification tools for currently used biomaterials to enhance tissue regeneration efficacy. These results may expand the feasibility of combinative strategy of controlled local drug delivery concept and tissue engineered bone formation in reconstructive therapy in the field of periodontics, orthopedics and plastic surgery. PMID- 11772461 TI - In situ forming degradable networks and their application in tissue engineering and drug delivery. AB - Multifunctional macromers based on poly(ethylene glycol) and poly(vinyl alcohol) were photopolymerized to form degradable hydrogel networks. The degradation behavior of the highly swollen gels was characterized by monitoring changes in their mass loss, degree of swelling, and compressive modulus. Experimental results show that the modulus decreases exponentially with time, while the volumetric swelling ratio increases exponentially. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Once verified, the proposed degradation mechanism was extended to correlate network degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems. A theoretical model utilizing a statistical approach to predict the cleavage of crosslinks within the network was used to predict the complex erosion profiles produced by these hydrogels. Finally, the application of these macromers as in situ forming hydrogel constructs for cartilage tissue engineering is demonstrated. PMID- 11772462 TI - Reducing capsular thickness and enhancing angiogenesis around implant drug release systems. AB - Biological encapsulation and the foreign body reaction can impair the performance of implanted drug release devices. In this article, the classic definition of biocompatibility is questioned. Examples are presented of biomaterials showing unique healing behavior. A new paradigm for biomaterials healing is proposed in which non-specific protein adsorption is inhibited and matricellular proteins are controlled at the surfaces of implants. PMID- 11772463 TI - Engineering endogenous inflammatory cells as delivery vehicles. AB - Leukocytes are central in directing host inflammatory and immune processes; therefore, leukocyte response to biomaterials is extremely important. Although several leukocyte-derived molecules are used clinically, the long-term efficacy of treatments involving the systemic administration of these bioactive agents has yet to be demonstrated. Hence, the localized delivery of selected cytokines and growth factors produced by endogenous leukocytes is desirable and may have potential therapeutic values in the fundamental processes of tissue healing, growth regulation, and biocompatibility. The specificity and diversity of ligand receptor interactions offer an attractive method in manipulating cellular behavior. Therefore, a more detailed understanding of the interplay between ligands and cell membrane receptors must be obtained. We designed interleukin-1 derived biomimetic agonists and antagonists to study and modulate leukocyte function in vitro. Selected agonists increased GM-CSF release by adherent human blood-derived macrophages in the presence of the natural IL1beta antagonist, namely IL1ra. Furthermore, IL1-derived biomimetic antagonists neutralized the ability of IL1beta in increasing the release of GM-CSF by adherent macrophages. We employed similar methodologies to elucidate the molecular mechanisms of integrin and extracellular matrix interaction in regulating leukocyte function. Oligopeptides were designed based on the functional structure of fibronectin and grafted on to a polymer network containing polyethyleneglycols. Macrophage adhesion was independent of the peptide identity that contained sequence RGD, PHSRN, PRRARV, or combinations thereof in an integrin-dependent fashion in vitro. However, integrin-dependent FBGC formation in vitro was highly dependent on both RGD and PHSRN in a single peptide formulation and with a specific orientation. From our intracellular signaling studies in vitro, protein tyrosine and serine/threonine kinases were found important in integrin signaling leading to macrophage adhesion mediated by fibronectin-integrin association. Furthermore, RGD and PHSRN appear to be significant in mediating this receptor-ligand association resulting in the necessary signaling characteristic for macrophage adhesion and the subsequent development. Our in vivo results showed that peptide identity played a minimal role in modulating the host inflammatory response and adherent macrophage density. RGD-containing peptides mediated rapid FBGC formation by 4 days of implantation by significantly increasing both the number of macrophages that participate in the cell fusion process and the rate of cell fusion. Both RGD and PHSRN domains were important in mediating FBGC formation at later implantation periods. These findings represent a mechanistic correlation between the role of protein functional architectures in ligand-receptor recognition and the post-ligation signaling events that control cellular behavior in vitro and in vivo. PMID- 11772464 TI - Surface modification of liposomes for selective cell targeting in cardiovascular drug delivery. AB - Cardiovascular disease processes such as atherosclerosis, restenosis, and inflammation are typically localized to discrete regions of the vasculature, affording great opportunity for targeted pharmacological treatment. Liposomes are potentially advantageous targeted drug carriers for such intravascular applications. To facilitate their use as drug delivery vehicles, we have considered three components of liposome design: (i) identification of candidate cell surface receptors for targeting; (ii) identification of ligands that maintain binding specificity and affinity; and (iii) prevention of rapid nonspecific clearance of liposomes into the reticuloendothelial organs. In this report, we describe our work in developing liposomal surface modifications that address both targeting and clearance. An arginine-glycine-aspartic acid (RGD) containing peptide was used as a model ligand to target liposomes to the integrin GPIIb-IIIa on activated platelets. Additionally, oligodextran surfactants incorporated into liposomes provided insight into the effect of vesicle perturbations on liposome clearance, and the importance of molecular geometry in designing oligosaccharide surface modifications. Together these studies demonstrate the feasibility of using peptides to guide liposomes to desired receptors, and illustrate the influence of vesicle stability on liposome interactions in vivo. Furthermore, they underscore the importance of simultaneously considering both targeting specificity and vesicle longevity in the design of effective targeted drug delivery systems. PMID- 11772465 TI - Electrophilic chelating agents for irreversible binding of metal chelates to engineered antibodies. AB - Radiolabeled monoclonal antibodies are widely used in the detection and treatment of cancer. However, several problems still prevent full clinical exploitation of these reagents. Low tumor/background ratios in radioimmunoscintigraphy and high background radioactivity in therapy are the foremost among these. The strategy of pretargeting which separates the tumor-targeting step from radiolocalization step may overcome these limitations. One pretargeting approach, based on the streptavidin-biotin system, has been demonstrated to successfully treat cancer in preclinical models (Proc. Natl. Acad. Sci. 97 (2000) 1802). In this report we describe the synthesis of several electrophilic chelates, designed for use in vivo. In this new pretargeting approach, we have used protein engineering to prepare an antibody that can bind selectively and irreversibly to certain of these metal chelates. This improves upon approaches based on the immunogenic protein streptavidin and the endogenous ligand biotin. PMID- 11772466 TI - Development of non-viral vectors for systemic gene delivery. AB - One of the major challenges for gene therapy is systemic delivery of a nucleic acid directly into an affected tissue. This requires developing a vehicle which is able to protect the nucleic acid from degradation, while delivering the gene of interest to the specific tissue and specific subcellular compartment. In this review, we summarize some of the recent advances in new non-viral delivery systems for systemic administration. Two types of gene delivery systems are described: (i) LPD1 (cationic liposome-entrapped, polycation-condensed DNA, type 1), and (ii) retention-time mediated naked DNA delivery. Hypothesized mechanisms for these systemic gene transfers are also discussed. PMID- 11772467 TI - What happens to negatively charged lipid vesicles upon interacting with polycation species? AB - Complexation of synthetic polycations with negative lipid vesicles as cell mimetic species was studied. It was found that such interaction could be accompanied by lateral lipid segregation, highly accelerated transmembrane migration of lipid molecules (polycation-induced flip-flop), incorporation of adsorbed polycations into vesicular membrane as well as aggregation and disruption of vesicles. A polycation adsorbed on the surface of liquid vesicles due to electrostatic attraction could be completely removed from the membrane by increase in simple salt concentration or by recomplexation with polyanions. In contrast, adsorption of a polycation carrying pendant hydrophobic groups was irreversible apparently due to incorporation of these groups into the hydrophobic part of the vesicular membrane. The above mentioned phenomena were examined depending on the polycation structure, fraction of charged lipids in the membrane, vesicle phase state and ionic strength of solution. PMID- 11772468 TI - Artery wall binding peptide-poly(ethylene glycol)-grafted-poly(L-lysine)-based gene delivery to artery wall cells. AB - Artery wall binding peptide (AWBP; Cys-Gly-Arg-Ala-Leu-Val-Asp-Thr-Leu-Lys-Phe Val-Thr-Gln-Ala-Glu-Gly-Ala-Lys), a specific targeting peptide, was conjugated to poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL) to enhance the gene transfer to artery wall cells. AWBP-PEG-PLL was synthesized by the reaction between the vinylsulfone group of PEG-g-PLL and the thiol group of cysteine in AWBP. 1H-NMR analysis confirmed the composition of the obtained polymer and indicated that four mol of AWBP were reacted to one mole of VS-PEG-PLL. The particles of AWBP-PEG-PLL/pDNA complexes were determined spherical with a size of approximately 100 nm by dynamic light scattering (DLS) and atomic force microscopy (AFM). Agarose gel retardation assay indicated that AWBP-PEG-PLL was able to condense plasmid DNA and reach complete complexation at and above a charge ratio 1/1 (+/-). Transfection efficiency of AWBP-PEG-PLL/pDNA complexes was 150-180 times higher than that of control systems, such as PEG-g-PLL/pDNA and PLL/pDNA, in both bovine aorta endothelial cells and smooth muscle cells. Luciferase activities of AWBP-PEG-PLL depended on the amount of free AWBP, while those of the control carriers such as PLL and PEG-g-PLL were not affected by free AWBP. These results supported that gene transfer of AWBP-PEG-PLL/pDNA complexes to bovine aorta wall cells was mediated by specific artery wall cell receptor mediated endocytosis. PMID- 11772469 TI - Therapeutic angiogenesis for critical limb ischemia: invited commentary. AB - Lower extremity arterial occlusive disease results in tissue ischemia of the legs and is relatively common in the elderly. Clinically, it may be asymptomatic, cause muscle pain during exercise, or progress to a severe degree of ischemia that may result in limb loss. Although bypass surgery and angioplasty have increased the rate of limb salvage in these patients, amputation of the affected limb remains a common outcome for many patients. Therapeutic angiogenesis is the administration of angiogenic factors, or genes encoding these factors, to promote neovascularization and thereby increase blood flow to the ischemic leg. We have developed an animal model of hindlimb ischemia in which to study therapeutic angiogenesis. We chose nitric oxide as the angiogenic factor for our experiments because of its ability to induce angiogenesis, vasodilation, and inhibit inflammation. In this review, we will discuss our experience with our model of hindlimb ischemia, as well as discuss our results of gene therapy for therapeutic angiogenesis using nitric oxide. PMID- 11772470 TI - pH-sensitive polymers that enhance intracellular drug delivery in vivo. AB - Cytosolic delivery from endosomes is critical for those drugs that are susceptible to attack by lysosomal enzymes, such as DNA, RNA, oligonucleotides, proteins and peptides. Therefore, we have designed pH-sensitive, membrane disruptive polymers to enhance the release of drugs from the acidic endosomal compartment to the cytoplasm. We have found that one polymer in particular, poly(propylacrylic acid) (PPAA), is very effective at membrane disruption at pHs below 6.5, based on hemolysis studies. PPAA also significantly enhances in vitro transfections of lipoplex formulations in cell culture, and does so in the presence of as much as 50% serum. In this study, we have extended our in vitro hemolysis and cell culture studies to an in vivo murine excisional wound healing model. A pilot study with a green fluorescent protein (GFP)-encoding plasmid indicated that injection of formulations containing PPAA into healing wounds resulted in increased GFP expression. Subsequently, by administering sense and antisense DNA for the angiogenesis inhibitor thrombospondin-2 (TSP2), we were able to alter the wound healing response in TSP2-null and wild type mice, respectively. Our findings showed that when PPAA was added to lipoplex formulations, expression of TSP2 was enhanced in TSP2-null mice compared to control formulations. These results show that PPAA can enhance in vivo transfections and that inhibition of TSP2 expression may lead to improved wound healing. These results suggest that PPAA can provide significant improvements in the in vivo efficacy of drugs such as DNA. PMID- 11772473 TI - Trauma and substance cue reactivity in individuals with comorbid posttraumatic stress disorder and cocaine or alcohol dependence. AB - Although the high comorbidity of posttraumatic stress disorder (PTSD) and substance use disorders has been firmly established, no laboratory-based studies have been conducted to examine relationships between the two disorders. Using cue reactivity methodology, this study examined the impact of personalized trauma image cues and in vivo drug cues on drug-related responding (e.g. craving) in individuals with PTSD and either crack cocaine (CD) or alcohol dependence (AD). CD and AD groups displayed reactivity to both trauma and drug cues when compared to neutral cues, including increased craving. However, the AD group was more reactive than the CD group to both classes of cues. The CD participants were more reactive to trauma-image cues if drug-related material was included in the image while the AD participants were reactive to the trauma cues regardless of drug related content. It is hypothesized that PTSD-related negative emotion may play a relatively more important role in the maintenance of AD when compared to CD. Evidence that substance dependent individuals with PTSD report increased substance craving in response to trauma memories is offered as a potential contributing factor in the poorer substance abuse treatment outcomes previously documented in this comorbid population. PMID- 11772472 TI - Drug dependence, parenting responsibilities, and treatment history: why doesn't mom go for help? AB - Despite longstanding concern that the presence of children deters drug-dependent women from entering treatment, there have been few empirical tests of the relationship between parenting responsibilities and treatment-seeking behavior. In this study, the relationship between number of biological children and treatment history was examined in a cohort of 153 women seeking methadone maintenance treatment. In a standard multiple regression analysis that also allowed for the potential influence of (a) age, (b) education, (c) ethnic minority status, (d) cohabitation with a sexual partner, (e) chronicity of opioid use, and (f) knowledge of HIV infection, there was a significant, negative relationship between number of children and number of earlier contacts for drug abuse treatment. Ethnic minority status and cohabitation with a sexual partner were also associated with fewer earlier contacts; greater chronicity and knowledge of HIV infection were associated with more earlier contacts. Moreover, there was significant moderation of the negative relationship between parenting responsibilities and treatment history by (a) ethnic minority status, (b) cohabitation, and (c) chronicity of use. Within a cross-sectional research design, the findings highlight ways parenting responsibilities may interact with other factors over time to influence the treatment-seeking behavior of drug dependent women. PMID- 11772474 TI - Cerebral blood flow pulsatility deficits in HIV+ poly substance abusers: differences associated with antiviral medications. AB - This study examines the influence of HIV-seropositivity and antiviral medications on cerebral blood flow in cocaine abusers. Forty-five HIV negative (HIV-) cocaine abusers, 36 HIV positive (HIV+) cocaine abusers (CD4; mean 378, +/-229) and 27 control HIV- subjects were studied. Blood flow velocity and pulsatility were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography (TCD). Psychological assessments, which included the psychiatric symptom checklist (SCL-90R), hopelessness (Beck) and well-being (Ellison) questionnaires revealed greater psychiatric distress in HIV+ cocaine abusers than the other groups. HIV- cocaine abusers and HIV+ cocaine abusers not receiving antiviral medications (n=25 of 36) had elevated pulsatility values, indicating increased resistance in the cerebral blood vessels in comparison to control subjects. HIV+ cocaine abusers using antiviral medications (n=11 of 36) had pulsatility values similar to HIV- control subjects. Interestingly, there was no significant relationship between intensity of psychiatric distress reported by HIV+ cocaine abusers and perfusion deficits. Our findings suggest that unmedicated HIV+ cocaine abusers have cerebrovascular deficits, which are similar to HIV- cocaine abusers. In addition, the use of antiviral medications appears to be associated with a reduction of these deficits in HIV+ cocaine abusers. Nevertheless, more studies will be needed before any conclusion can be reached regarding possible beneficial effects of these agents on the cerebral vasculature. PMID- 11772476 TI - Diagnostic interview for genetic studies (DIGS): inter-rater and test-retest reliability of alcohol and drug diagnoses. AB - The semi-structured diagnostic interview for genetic studies (DIGS) was developed to assess major mood and psychotic disorders and their spectrum manifestations in genetic studies. Our research group developed a French version of the DIGS and tested its inter-rater and test-retest reliability in psychiatric patients. In this article, we present estimates of the reliability of substance use and antisocial personality disorders. High kappa coefficients for inter-rater reliability were found for drug and alcohol as well as antisocial personality diagnoses and slightly lower kappas for test-retest reliability. Combined with evidence of the reliability of major mood and psychotic disorders, these findings support the suitability of the DIGS for studies of familial aggregation and comorbidity of psychiatric disorders including substance use and antisocial personality disorders. PMID- 11772475 TI - A multicenter randomized evaluation of methadone medical maintenance. AB - Methadone medical maintenance (MMM) is a rational, cost-effective method to match treatment intensity to level of needed services. In the present study, 73 highly stable methadone maintenance patients were randomly assigned to either a routine methadone treatment, MMM--a once monthly reporting schedule--at the methadone maintenance program or MMM at a physician office. A 'stepped care' intensified treatment approach was used for patients who had drug-positive urine specimens or failed the medication recall procedure. Patients left two urine specimens for analysis each month (at least one on a random basis) and responded to one medication recall each month. Results are presented for the first 6 months of the 1-year trial. Only 1% of urine specimens were positive for illicit drugs, there was no evidence of methadone diversion and there were very low rates of medication misuse, with no between group differences. MMM patients initiated more new employment or family/social activities than the routine care patients. MMM patients were more satisfied with their treatment than the routine treatment patients, but all patients rated themselves satisfied or very satisfied with their treatment. Stepped care was well-tolerated and helped match patients to an appropriate intensity of service. The good outcomes observed with the present sample suggest that MMM can be implemented effectively as part of a continuum of care in clinic and office-based sites. PMID- 11772477 TI - Is long-term heavy alcohol consumption toxic for brain serotonergic neurons? Relationship between years of excessive alcohol consumption and serotonergic neurotransmission. AB - The relationship between years of excessive alcohol consumption and central serotonergic neurotransmission, as assessed by the prolactin (PRL) response to D fenfluramine, was investigated in 22 male alcohol-dependent subjects. A negative correlation was obtained, that is, the longer duration of excessive alcohol consumption the lower PRL response to D-fenfluramine. It is therefore suggested that long duration of excessive alcohol consumption in alcohol-dependent subjects causes a reduction in central serotonergic neurotransmission, possibly by a toxic effect of alcohol on serotonin neurons. The relationship between depressive and anxiety symptoms during on-going drinking and the PRL response to D-fenfluramine was also investigated. No such correlations were obtained, suggesting that reduction in central serotonergic neurotransmission does not pre-dispose to the development of depressive and anxiety symptoms, at least in relation to on-going drinking in alcohol-dependent subjects. PMID- 11772478 TI - Developmental trajectories of cigarette use from early adolescence into young adulthood. AB - This study identified developmental trajectories of cigarette smoking from early adolescence into young adulthood, and delineated whether risk factors derived from a social learning-problem behavior framework could differentiate among trajectories. Participants (N=374) were interviewed five times from age 12 until age 30/31. Using growth mixture modeling, three trajectory groups were identified -heavy/regular, occasional/maturing out, and non/experimental smokers. Being a female, having higher disinhibition, receiving lower grades, and more frequent use of alcohol or drugs significantly increased the probability of belonging to a smoking trajectory group compared with being a nonsmoker. Higher disinhibition and receiving lower grades also differentiated regular smokers from the rest of the sample. None of the risk factors distinguished occasional from regular smokers. When models were tested separately by sex, disinhibition, other drug use, and school grades were associated with smoking for both sexes. On the other hand, environmental factors, including socioeconomic status, parent smoking and friend smoking, were related to smoking for females but not for males. Sex differences in developmental trajectories and in smoking behavior among regular smokers were notable. Future research should examine transitions and turning points from adolescence to adulthood that may affect cessation and escalation differently for males and females. PMID- 11772479 TI - Voucher-based reinforcement of opiate abstinence during methadone detoxification. AB - Methadone detoxification is often used in the treatment of opiate dependence. This procedure, however, is frequently associated with continued opiate use, and high rates of attrition and relapse. In this study, a 90-day methadone detoxification was enhanced by adding voucher-based reinforcement of opiate abstinence before, during and after the dose tapering schedule. After 4 weeks of standard methadone maintenance (baseline), subjects were randomized to either the abstinence (n=26), or attendance reinforcement (n=22) condition. During the remaining 22 weeks of the study, the abstinence reinforcement group could receive vouchers with monetary value three times per week for providing opiate-negative urine specimens, while subjects in the attendance reinforcement group received vouchers of equal value for attending the clinic, regardless of urinalysis results. Methadone maintenance continued during weeks 5-10, dose tapering was implemented during weeks 11-23, and during weeks 24-26 the voucher schedule remained in effect but no medication was provided. Fifty percent of clients in both groups completed dose tapering, and 40% completed the vouchers-only phase. Subjects in the abstinence as compared with the attendance reinforcement group had lower rates of opiate use during the maintenance and detoxification phases, and longer periods of opiate abstinence during the detoxification phase. Cocaine use was also lower in the abstinence than the attendance reinforcement group during the maintenance and detoxification phases. In addition, abstinence as compared with attendance reinforcement subjects reported significantly fewer intravenous injections during the detoxification phase. Voucher-based reinforcement procedures could be useful for successfully transitioning patients into opiate antagonist therapy, or drug-free treatments. PMID- 11772480 TI - Detecting smoking following smoking cessation treatment. AB - Our study compared the results of self-report (SR) plus breath carbon monoxide (CO) monitoring to SR plus urine cotinine (COT) analysis of recent tobacco use for a recently completed smoking cessation study that compared the efficacy of different intensities of psychosocial treatments coupled with 8 weeks of patch treatment. Treatment outcomes were assessed 9, 26, and 52 weeks from treatment initiation in 200+ patients using both measurement types. COT was able to detect self-reported smoking in over 97% of the cases at all time points, while CO detected self-reported smoking 62, 84, and 89% of the time for the three follow up assessments. Under 2% of those reporting nonsmoking were found to be smoking via CO, whereas COT found smoking to have occurred for 23, 15, and 7% of the 'nonsmoking' SRs at the three time points. Abstinence rates using SR plus CO were 49, 29, and 26%, contrasted with abstinence rates of 38, 26, and 25% for SR plus COT. These findings suggest that use of urine analysis for COT may lead to more accurate but lowered measured abstinence rates. PMID- 11772481 TI - Buprenorphine prescription by general practitioners in a French region. AB - Since 1996 French general practitioners (GPs) may prescribe sublingual buprenorphine tablets as maintenance treatment for opiate dependence. The computerised data management of the main French health reimbursement system now allows surveillance of the use of this drug, and how it is prescribed. The purpose of this study is to determine the profile of maintained patients, prescribed doses, associated psychotropic treatments and how practitioners prescribe these treatments. This study analyses the 11186 buprenorphine prescriptions electronically transmitted for reimbursement between September and December 1999 in a specific French region. It was found that the 2078 treated patients consumed a mean of 11.5 mg of buprenorphine per day and 12% of them procured prescriptions from more than two prescribers. 43% of maintained patients had an associated benzodiazepine prescription, mainly flunitrazepam, often on the same prescription form. 61% of patients had regular follow-up, others had occasional consultations (21%) and another 18% had deviant maintenance treatment (more than two prescribers or more than 20 mg per day of daily buprenorphine dose). Benzodiazepine consumption was much higher in the 'deviant group' (71.4%). 85% of buprenorphine prescriptions were made by GPs. 21% of GPs prescribed buprenorphine and 61% of those had only one or two maintained patients. Buprenorphine prescription by French GPs is a procedure with no particular requirements, allowing many patients to easily access maintenance treatments. However, a high risk of abuse exists, which demands extensive investigation and evaluation of these practices. PMID- 11772482 TI - Measurement of the viscoelastic compliance of the eustachian tube using a modified forced-response test. AB - OBJECTIVES: Eustachian tube compliance (ETC) was suggested to be an important determinate of function. Previous attempts to quantify ETC used summary measures that are not clearly related to the physical properties of the system. Here, we present a new method for measuring ETC that conforms more closely to the engineering definition of compliance. METHODS: The forced response test was modified to include oscillations in applied flow after the forced tubal opening. Pressure and flow were recorded during the standard and modified test in 12 anesthetized cynomolgus monkeys. The resulting pressure-flow, hysteresis loops were compared with those predicted by a simple fluid-structure model of the Eustachian tube with linear-elastic or viscoelastic properties. The tubal compliance index (TCI) and a viscoelastic compliance (C(v)) were calculated from these data for each monkey. RESULTS: The behavior of a viscoelastic, but not a linear elastic model accurately reproduced the experimental data for the monkey. The TCI and C(v) were linearly related, but the shared variance in these measures was only 63%. CONCLUSIONS: This new method for measuring ETC captures all information contained in the traditional TCI, but also provides information regarding the contribution of wall viscosity to Eustachian tube mechanics. PMID- 11772483 TI - Reparative granuloma seen in cases of gold piston implantation after stapes surgery for otosclerosis. AB - OBJECTIVE: to determine the occurrence of the unusual side effect of a reparative granuloma after the implantation of a pure gold piston in cases of otosclerosis. STUDY DESIGN: a retrospective case review study of 475 stapes operations with a pure gold piston. SETTING: Department of Otorhinolaryngology of the University of Amsterdam, The Netherlands and the HNO clinic in Luenen (Brambauer) in Germany. PATIENTS: four hundred and seventy five patients (328 women, 147 men, average age: 45.2 years), who clinically and per-operatively had otosclerosis, underwent a stapedotomy using a pure gold piston prosthesis. Therapeutic intervention: in cases of suspicion of a reparative granulomas or those cases that did not have improvement of the hearing after the stapedotomy, a re-operation by transcanal approach was performed. RESULTS: in seven cases a reparative granuloma was diagnosed by this revision surgery. The postoperative incidence of these granulomas following stapedotomy using the pure gold piston turned out to be 1.5%. CONCLUSION: reparative granulomas can occur after stapedotomy with a pure gold stapes piston although the incidence is low. The role of grafting material to seal the oval window niche and the treatment of these reparative granulomas following stapes surgery are discussed. PMID- 11772484 TI - Evaluation of brainstem auditory evoked response audiometry findings in children with tuberculous meningitis at admission. AB - OBJECTIVE: To determine the characteristics of Brainstem auditory evoked response (BAER) findings in children with tuberculous meningitis (TBM) at admission. METHODS: Twenty-seven children with highly probable TBM were admitted to the University Hospital. The control group was 23 healthy, age and sex matched subjects. Brainstem response audiometry recording was performed in all patients and controls. Ninety dB sound pressure level (SPL) was used for comparisons. The main BAER measurements analysed were the I-III, III-V, I-V interpeak intervals. In statistical analysis, t-test for independent groups were performed. At the same time, for interpeak intervals, values exceeding 2.5 standard deviations (S.D.) above the means of the normal controls were considered abnormal. To the result of BAER findings, HL was classified as mild (until 40 dBHL), severe (until 80 dBHL) and total HL (no hearing was detected). RESULTS: The latencies of interpeak intervals (except III-V latency at 10 per s) have significantly prolonged in comparison with controls. Mild HL was detected in four ears. In eight ears, any wave form could not be obtained at 110 dBSPL. Abnormal BAER result was seen in 13 of 54 ears (24%) at the click of 10 per s and five ears (12%) at the click of 50 per s. CONCLUSION: Abnormal BAER result was seen in 24% of patients with TBM before treatment. Depending on these findings, it can be inferred that hearing impairments must be lower than those values which was detected by BAER during the acute phase of TBM, since the abnormal BAER may be reversible following the illness, returning to normal with recovery. PMID- 11772485 TI - Surgical treatment of 52 cases of auditory ossicular malformations. AB - OBJECTIVE: The aim of this study was to determine the relationship between hearing improvements and the pathological conditions of auditory ossicular malformations. METHODS: Fifty-two ears (49 patients) with auditory ossicular malformations without congenital aural atresia were studied. The classification of the pathological conditions was based on surgical findings. Group 1 showed defects in the incudo-stapedial (I-S) joint, Group 2, fixation of the stapes, Group 3, fixation of the malleus and incus and Group 4, defects in the I-S joint with fixation of the stapes. Hearing improvements at the final examination were designated as successful when both of the following were satisfied. (1) Air-bone gap was reduced to 20 dB or less. (2) Postoperative hearing gain exceeded 15 dB. RESULTS: Successful hearing improvements after operations were achieved in 20 ears (95%) in Group 1, 21 ears (91%) in Group 2, three ears (75%) in Group 3 and two ears (50%) in Group 4. They were observed in 88% of all cases. CONCLUSIONS: Postoperative hearing improvements of auditory ossicular malformations yielded good results, particularly in Groups 1 and 2. In retrospect, the unsuccessful cases with fixation of the stapes would have been improved if stapedectomy were chosen rather than mobilization. In defects to the long process of Group 4, we wished to perform a reconstruction using the malleus attachment piston after small-fenestra stapedectomy with regard to the long-term hearing results. PMID- 11772486 TI - Clinical characteristics of so called eosinophilic otitis media. AB - OBJECTIVE: Although "eosinophilic otitis media" is not as uncommon a condition as was previously believed, its cause and pathogenesis are not yet fully understood. The purpose of this study was to describe the clinical characteristics in patients with "eosinophilic otitis media" to clarify its pathogenesis. METHODS: Seven adult patients with persistent and intractable otitis media with viscous middle ear effusion containing many eosinophils, who were also under treatment for bronchial asthma, were studied. The following examinations were conducted: nasopharyngeal endoscopy, pure-tone audiometry, eustachian tube function test, temporal bone CT scan, blood analysis, bacterial and fungal culture of middle ear effusion, histological study of the middle ear and nasal specimens, and measurement of eosinophilic cationic protein (ECP) in middle ear effusion. RESULTS: Some patients had persistent perforation with papillomatous granulation tissue arising from the mesotympanic mucosa, and all the patients had nasal polyposis. The pure-tone audiometry showed the mixed-type of hearing loss in all the patients, and the hearing level deteriorated progressively during the course in some patients. The eustachian tube function was not always poor but was patulous in some cases. The most severely diseased areas were in the eustachian tube and mesotympanum by temporal bone CT images. All the seven patients had the high levels of total serum IgE, but the RAST scores were negative in three patients and low grade in three patients. The accumulation of eosinophils was observed in middle ear effusion, middle ear mucosa and nasal polyps, and the eosinophils were highly activated with degranulation. High level of ECP was also recovered from middle ear effusion. CONCLUSIONS: Active eosinophilic inflammation occurs in the entire respiratory tract, including the middle ear in these patients. From our present investigation, we propose the criteria and clinical characteristics of "eosinophilic otitis media". PMID- 11772487 TI - DPOAEs and vestibular function in different types of autosomal-dominant non syndromal hearing impairment. AB - BACKGROUND/OBJECTIVE: The application of distortion-product otoacoustic emissions (DPOAE) could be advantageous in the early diagnostic of descendants of families with autosomal-dominant non-syndromal hearing impairment (ADNSHI). PATIENTS/METHODS: DP-grams of 58 affected persons of 21 families with ADNSHI were measured (f(2)/f(1)=1.22; L(1)=70 dB SPL; L(2)=65 dB SPL; four points per octave). The mode of transmission was determined by pedigree. The phenotype was determined by pure tone audiometry (PTA) and caloric vestibular test (CVT). RESULTS: We could find 12 families with mild to severe mid-frequency U-shaped ADNSHI, three families with steeply sloping high tone ADNSHI, two families with moderate to severe gently sloping high tone ADNSHI, three families with profound ADNSHI and one family with variable ADNSHI. One family showed an additional vestibular lesion. Fifty-six of 58 affected persons showed pathological DP-grams. In 48 persons (83%) these DP-grams showed distinct similarity within the families, that they could be classified as "ADNSHI-typical" within an affected family. CONCLUSIONS: Affected persons of a family with ADNSHI show similar DP grams. These DP-grams are useful in the early routine-diagnostics of newborns within such families. PMID- 11772488 TI - Olfactory dysfunction in patients with head trauma. AB - OBJECTIVE: There are few reports about following up olfactory acuity of the patients who have post-traumatic olfactory dysfunction. In this study, we studied about patients with post-traumatic olfactory dysfunction for a short period under a treatment. METHODS: The olfactory function of 27 patients with head trauma was studied. The olfactory acuities of all the patients were examined using olfactory tests before the treatment, and 18 patients were examined again after the treatment. Olfactory functions were evaluated in 26 patients by T&T olfactometry and in 27 patients by Alinamin test. All of the patients were treated with a local injection of suspended steroid solution into the nasal mucosa [J Otolaryngol Jpn 102 (1999) 1175]. RESULTS: Before the treatment, 16 patients (61.5%) presented anosmia, five patients (19.2%) presented severe hyposmia, three patients (11.5%) presented moderate hyposmia, and two patients (7.7%) presented mild hyposmia. Eighteen cases (69.2%) were negative for the Alinamin test and eight cases (30.8%) were positive. The improvement rates of recognition and detection thresholds by T&T olfactometry were 35.3 and 23.5%, respectively. CONCLUSION: Olfactory dysfunction caused by head trauma can be recovered to a limited degree in some cases by the local injection of steroid within the relatively short period from the start of the therapy. PMID- 11772489 TI - Causes of recurrent laryngeal nerve paralysis. AB - OBJECTIVE: Persistent hoarseness due to recurrent laryngeal nerve paralysis (RLNP) reduces the quality of life unless it is adequately treated. This study examined the indications for phonosurgical intervention in patients with RLNP. MATERIALS AND METHODS: The medical records of the Ehime University Hospital, Ehime, Japan, from October 1976 until December 1997 were reviewed retrospectively to identify patients with RLNP. The data collected included age, gender, paralyzed side, and cause of paralysis. RESULTS: Four hundred and sixty-six patients with RLNP were identified: 262 males and 204 females. Unilateral RLNP was present in 422 patients, while 44 presented with bilateral RLNP. The incidence was relatively high in the 7th and 8th decades, and was twice as high in male patients as in female patients. The 466 patients were divided into 2 groups: Group 1 included 225 patients seen before January 1987, and Group 2 included 241 patients seen after this date. The number of patients with postoperative RLNP was significantly higher in Group 2 (124 of 239 patients) than in Group 1 (65 of 227 patients) (P<0.05). Surgery for cardiovascular disease, esophageal cancer, and skull base and thyroid gland tumors contributed to this increased incidence of postoperative RLNP. CONCLUSIONS: Patients with persistent unilateral RLNP require appropriate treatment for hoarseness, regardless of its cause. Since the incidence of RLNP related to surgery was significantly increased in Group 2, phonosurgery has become more important for improving the quality of life of these patients. PMID- 11772490 TI - Metastatic head and neck squamous cell carcinoma to the brain. AB - BACKGROUND: To evaluate the natural history of patients with metastatic squamous cell carcinoma (SCCA) of the head and neck to the brain. METHODS: A retrospective review of patients with brain metastases treated over a 20-year period identified five that had a head and neck SCCA primary. RESULTS: Five cases of patients with SCCA of the head and neck that developed brain metastases are presented in detail. CONCLUSION: In patients with aggressive disease, large infiltrative lesions, and in late survivors with initially advanced disease, metastasis to the brain should be considered. Perineural metastasis appears to be the most common mode of spread of head and neck SCCA to the brain. Pain, paresis, or paresthesias in the distribution of cranial nerves or other neurological symptoms should alert the otolaryngologist to neural or central nervous system involvement in patients with SCCA of the head and neck. Surgery with or without post-operative whole brain radiation therapy is the mainstay of treatment in most patients. Stereotactic radiosurgery may play a major role in treating brain metastases from head and neck primary tumors. PMID- 11772491 TI - Diagnosis of the elongated styloid process by three-dimensional computed tomography. AB - OBJECTIVE: To examine whether the styloid process can be imaged by three dimensional computer tomography reconstruction (3-DCT) distinctly enough to be used for diagnosis, and whether the image findings are explanatory of the symptoms. METHODS: We performed 3-DCT in four patients suspected to have elongated styloid process in our hospital. The apparatus we used was X-vigor (Toshiba), and the processing software was X-tension; the slicing thickness was 1.0 mm and the shifting speed of CT table was 1.0 mm per rotation. One hundred and twenty images were reconstructed for a view. RESULTS: In all cases, the 3-DCT showed the exact full length of the styloid process. Two cases were diagnosed as elongation of the styloid process by 3-DCT and their image findings were explanatory of the symptoms. In other two cases, the 3-DCT showed no difference between the right and the left styloid processes, and thus the diagnosis of elongation of the styloid process had to be excluded. CONCLUSION: We suggest that 3-DCT is useful for the diagnosis, explanation to patients and selection of treatment in some cases of elongated styloid process, but further study in more cases is required before we can fully confirm the utility. PMID- 11772492 TI - Contemporary trends in microbiology and antibiotic resistance in otolaryngology. AB - OBJECTIVE: to determine current microbiologic yields and characterize antibiotic resistance patterns for organisms cultured from head and neck infections. METHODS: results of out-patient cultures submitted from an academic otolaryngology practice over the period 1994-1998 were reviewed. A database was constructed, and culture results were analyzed for sites of infection, organism recovery rate, infecting microbiological agent, antibiotic resistance patterns, and 5-year trends. chi(2) analysis was used to determine associations between site of infection, infecting agent and antibiotic resistance over the years of the study. RESULTS: a total of 986 aerobic cultures were reviewed. The most common sites cultured were the nose/paranasal sinuses (469), throat (377), and ear (23). In 465 (47.2%) cultures, normal flora or no growth occurred. Of the throat culture subset, 69.7% were negative, whereas 69.1% of sinonasal cultures recovered organisms. Gram positive cocci were the most commonly recovered organism type (30.9%), followed by Gram negative rods (GNR, 17.2%). These rates remained relatively constant over the years of the study. GNR were found in 39.1 and 25.2% of ear and sinus cultures, respectively. Antibiotic sensitivities were conducted on 257 specimens (49.3% of positive cultures). The average number of antibiotic resistances per bacteria remained stable at approximately 1.59 over the years (P=0.086, analysis of variance (ANOVA)). Antibiotic resistance rates increased for clindamycin, cefazolin, and erythromycin over the years of the study (P<0.05, chi(2)). Ciprofloxacin, gentamicin and trimethoprim sulfamethoxazole resistance rates did not increase over the years of the study. Vancomycin resistance did not occur. CONCLUSIONS: as a significant proportion of head and neck cultures will be negative, their utility should be re-examined. GNR infections are more common in the head and neck than earlier thought. There is a trend towards increasing antibiotic resistance in head and neck infections, urging careful and appropriate use of antibiotics. PMID- 11772493 TI - Endoscopic trans-nasal-vestibular approach to the maxillary sinus--application for mucoceles of the maxillary sinus. AB - Endoscopic endonasal surgery has been applied to the treatment of paranasal mucoceles. The approach is, however, hard to be adopted for maxillary mucoceles when the cyst is situated in the anterior and/or lateral portion of the maxillary sinus, has a thick bony lateral wall of the inferior nasal meatus, and when the patients develop compartmentalized cysts following facial trauma or sinus operation. We devised an endoscopic approach via the vestibule of the nose to reach any part of the maxillary sinus and applied it for the treatment of postoperative maxillary mucoceles, which could not be opened following the usual endoscopic approach with favorable outcomes. PMID- 11772494 TI - The intracranial complication of acute isolated sphenoid sinusitis. AB - Acute isolated sphenoid sinusitis is a rare, potentially destructive entity, which has indistinct clinical findings and non-specific symptoms. Hence, it can be easily be misdiagnosed. We present and discuss a case of an isolated sphenoiditis with intracranial complication. PMID- 11772495 TI - A case of laryngeal aspergillosis following radiation therapy. AB - Primary laryngeal aspergillosis is extremely rare. It is commonly seen as a part of a systemic infection involving the respiratory system in an immunocompromised host. Differential diagnosis is important, as the clinical symptoms are similar to those of malignant laryngeal disease. We describe a 73-year-old man with a history of hoarseness. He had a history of radiotherapy for laryngeal squamous cell carcinoma and had a history of diabetes. Direct laryngoscope and biopsy confirmed the diagnosis of aspergillus. We cauterized the lesion with a CO(2) laser. In the present case, irradiation seemed to have played a more important role in the onset of this disease rather than diabetes. PMID- 11772496 TI - Adenoid cystic carcinoma of the lacrimal gland with wide and severe myoepithelial differentiation. AB - Adenoid cystic carcinoma (ACC) of the lacrimal gland is the second most common epithelial tumor for which different biologic courses can be predicted by histologic criteria. Three main types of growth patterns, cribriform; tubular; and solid have been identified. Tumors with solid components frequently follow a more aggressive clinical course and show worse prognosis than those with other patterns. We herein report a case of ACC with wide and severe myoepithelial differentiation arising from the lacrimal gland and presenting with aggressive clinical behavior. Postoperative radiotherapy may be the treatment of choice to control residual lesions and provide long-term survival even in the case of incomplete resection. Despite extensive surgery and radiation therapy, the prognosis of these tumors, especially with solid components, remains extremely poor. Accurate diagnosis is important because tumor histopathology is generally believed to be the most significant factor in patient survival. PMID- 11772497 TI - Surgical management of recurrent parathyroid cyst. AB - Parathyroid cysts are rare lesions of uncertain embryological origin, usually presenting as a painless mass in the lower part of the neck. Clinical presentation usually mimics a thyroid nodule, and fine needle aspiration with demonstration of high parathyroid hormone levels in fluid is often required to establish the diagnosis. In addition to difficulty in diagnosis, the best treatment for these uncommon lesions remains controversial. We present a case of recurrent parathyroid cyst after several fine needle aspirations managed by surgery, and discuss the relevant associated literature. PMID- 11772498 TI - Papillary cystadenocarcinoma arising from minor salivary glands in the anterior portion of the tongue: a case report. AB - Papillary cystadenocarcinoma is a rare malignant neoplasm of the salivary gland. We report a case of papillary cystadenocarcinoma arising from the minor salivary gland in the anterior portion of the tongue of a 72-year-old male patient with a history of adenocarcinoma of the colon and prostate. Further, we discussed histopathological and clinical features of this lesion, and reviewed the literature. PMID- 11772499 TI - Malignant myoepithelioma arising from recurrent pleomorphic adenoma of minor salivary gland. AB - Malignant myoepitheliomas of the salivary gland are very rare tumors which may either arise de novo or develop in a pre-existing pleomorphic adenoma. We report a case of malignant myoepithelioma of the minor salivary gland that progressed from benign pleomorphic adenoma. The original pleomorphic adenoma was resected in 1979 (the '79 tumor). The first recurrent tumor was operated in 1995 (the '95 tumor). The '95 tumor was diagnosed as pleomorphic adenoma. Although the myoepithelial tumor component was more prevalent in the '95 tumor, histological features of the first recurrent tumor were similar to the '79 tumor. The second recurrent tumor showed more aggressive clinical features (the '98 tumor). It also showed massive growth of myoepithelial tumor cells with bone invasion, which led to the diagnosis of the '98 tumor as malignant myoepithelioma. With adequate surgical margin, the patient has been free from tumor recurrence for 20 months. PMID- 11772500 TI - Radiosensitive hemangiopericytoma in the soft palate. AB - Hemangiopericytomas are uncommon neoplasms of vascular origin, and rarely arise in the pharynx. We report a case of a 78-year-old female with hemangiopericytoma in her soft palate exhibiting prominent radiosensitivity. Hemangiopericytomas are considered to be radioresistant and wide local excision is a treatment of choice, but their nature is widely variable. In treating aggressive hemangiopericytomas, radiation therapy can be selected. PMID- 11772501 TI - Ischaemic necrosis and facial palsy in Warthin's tumour of the parotid gland. AB - A 72-year-old patient with a Warthin's tumor of the right parotid gland developed massive necrosis of the tumour associated with temporary facial palsy with subsequent macroscopic tumour disappearance. PMID- 11772502 TI - Basic biology and clinical impact of immunosenescence. AB - Immunosenescence is an age-associated decline of immunity involving multiorgan changes. As the mean age of the population increases, an increase of diverse pathologies associated with immunosenescence has been observed in the developed countries. Age-related changes in the immune system contribute to the increased incidence and severity of infectious diseases and possibly cancer in the elderly. Moreover, in young individuals chronic activation of the immune system (as occurs in autoimmune diseases, cancer, HIV infection and other chronic infections) induces changes in the immune response that parallel those observed in elderly individuals. An interdisciplinary approach to immunosenescence including investigation of the molecular and cellular mechanisms and clinical aspects is being utilised by the EU program "Immunology and Ageing in Europe" (ImAginE, QLK6 CT-1999-02031), the second major international conference of which took place in Cordoba, Spain, 22-26th March, 2001). We briefly summarise some of the highlights of the meeting here, and bring together in this special issue a collection of peer-reviewed papers reflecting the broad approach to immunosenescence currently being applied. PMID- 11772503 TI - Hematopoietic cells and replicative senescence. AB - Replicative senescence describes the finite cell replicative capacity in response to chronic proliferative stimulation. A key element in this process is the shortening of the telomeres, which to a major extent is caused by the lack of expression of telomerase. Whereas this situation has been well documented for a variety of somatic cell types, the question of whether stem cells "senesce" in the course of enforced chronic sequential divisions is as yet unresolved. This article examines several distinct features of hematopoietic cells (HC) in light of their similarity to certain aspects of memory T cells. It appears that although the capacity of HC for replication is not exhausted under normal physiological conditions in vivo, under certain experimental conditions and in specific in clinical situations HC do show signs of telomere shortening. This limited potential should be taken into account both with respect to aging in vivo, and also in terms of attempts to expand these cells ex vivo for therapeutic use. PMID- 11772504 TI - Intestinal mucosal immunosenescence in rats. AB - The elderly are characterized by systemic immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Despite the consensus that the mucosal immune compartment is largely unaffected by aging, there are marked deficits in the intestinal mucosal immune responses of old animals and elderly humans. However, little is known about the mechanism(s) whereby aging disrupts intestinal immunity. Events in the generation of an intestinal immune response may be susceptible to the insults of aging. The first step involves the uptake of antigens by specialized follicular epithelial cells (M cells). There have been no studies on the efficacy of antigen uptake by M cells as a function of age. Little is known about the next step, i.e. antigen presentation by dendritic cells and subsequent isotype switching. The third event is the differentiation of putative immunolobulin A (IgA) plasma cells and their homing from the Peyer's patches (inductive site) to the lamina propria of the small intestine (effector site). Quantitative immunohistochemical and flow cytometry analyses suggest that the homing of IgA immunoblasts may be compromised in old rats and monkeys. Local antibody production/secretion by mature IgA plasma cells in the intestinal wall constitutes the fourth step. In vitro anti-cholera toxin IgA antibody secretion by intestinal lamina propria lymphocytes is equivalent in cells isolated from young adult and senescent rats. The final event in the mucosal immune response is the transport of IgA antibodies across the mucosal epithelial cells and their secretion onto the mucosal surface, i.e. receptor-mediated vesicular translocation of IgA by the intestinal epithelial cells. Binding assays did not detect age-associated declines in either the number or binding affinity of the polymeric immunoglobulin receptor expressed on rodent and monkey intestinal epithelial cells. PMID- 11772505 TI - Gamma/delta T lymphocytes are affected in the elderly. AB - gammadelta T lymphocytes are considered to represent a link between the inflammatory response and adaptive immunity. In the present paper we investigated whether these cells play any role in the remodeling of the immune system described in the elderly. We show that the absolute number of gammadelta T cells in peripheral blood of old and very old subjects is reduced. Moreover, gammadelta T cells from old people and centenarians show enhanced levels of the early activation marker CD69 both after culture in medium alone and in LPS-stimulated cells. Furthermore, they show a basal increased production of tumor necrosis factor (TNF)-alpha as evaluated at the single cell level. Additionally, the response of these cells to IPP in "in vitro" cultures is in part impaired. These results suggest that the high level of basal activation of gammadelta T cells is due to the "inflamed" environment. However, the changes in number and function of gammadelta T lymphocytes might influence the resolution of inflammatory immune responses in the elderly. PMID- 11772506 TI - Valpha24+ NKT cells are decreased in elderly humans. AB - Natural killer T (NKT) cells represent a novel cell lineage characterized by the restricted expression of an invariant TCRalpha chain encoded by Valpha24/JalphaQ gene segments in humans and Valpha14/Jalpha281+ in mice. Different aspects of the immune response are severely affected by age. Thus, we have studied the effect of aging on NKT cells from healthy elderly individuals. Our results demonstrated a decreased percentage of CD3+Valpha24+ cells in peripheral blood from elderly donors, whereas mainstream T lymphocytes showed an age-associated decrease in the expression of CD28, the vast majority of CD3+Valpha24+ cells from old individuals were CD28+. A significant increase in the percentage of Valpha24+ cells with the CD4-CD8+ phenotype was also found in the elderly, indicating a redistribution of Valpha24+ subsets according to the CD4/CD8 phenotype. Given the important immunoregulatory role of these cells, the decrease of NKT cells will contribute to the deleterious immune response in the elderly. PMID- 11772507 TI - RANTES and MIP-1alpha production by T lymphocytes, monocytes and NK cells from nonagenarian subjects. AB - While numerous previous studies have investigated age-related changes of cytokine production, little is known about chemokines, the importance of which in regulating immune response is becoming increasingly evident. In this study, a group of healthy subjects over 90 years old is compared to a group of young subjects, we evaluated the ability of monocytes, T lymphocytes and NK cells: (1) to produce RANTES and MIP-1alpha, either in basal conditions or after stimulation with, respectively, LPS, anti-CD3 MoAb and IL-2; (2) to express the corresponding chemokine receptors (CCR1, CCR3, CCR5). We demonstrate that: (a) monocytes, T lymphocytes and NK cells spontaneously produced detectable amounts of chemokines, both in young and old subjects; (b) monocyte-dependent RANTES and MIP-1alpha production induced by LPS was up-regulated in nonagenarian subjects as anti-CD3 induced secretion from T cells; (c) RANTES and MIP-1alpha production by IL-2 stimulated NK cells was reduced in elderly subjects; (d) CCR1, CCR3 and CCR5 were widely expressed on monocytes, but less expressed on T lymphocytes and NK cells. The diversity within PBMC might reflect their different states of activation and/or responsiveness, influencing the ability to develop rapid innate and long lasting adaptive immune responses. PMID- 11772508 TI - A whole blood method for measurement of intracellular TNF-alpha, IFN-gamma and IL 2 expression in stimulated CD3+ lymphocytes: differences between young and elderly subjects. AB - Cytokines, the central regulators of leucocyte growth and differentiation, are produced by a wide variety of cell types, target various cell subsets and exhibit numerous biological activities. Cytokine dysregulation is believed to play a role in the remodelling of the immune system in old age, however, previous reports of cytokine levels in elderly subjects have been conflicting, possibly due to methodologies employed. We used the relatively new technique of intracellular cytokine detection by flow cytometry to measure cytokine production in CD3+ lymphocytes from young and elderly subjects, but applied it to whole blood, thereby eliminating the need for laborious cell separation techniques and maintaining cells in their normal physiological environment. We found the assay to be very reproducible with acceptable intra- (2.9%) and inter- (6.3%) assay CVs. The percentages of CD3+ cells producing TNF-alpha and IFN-gamma were significantly higher in elderly compared to young people (p=0.0049; p=0.0026, respectively) after stimulation with PMA and ionomycin. Absolute counts of CD3+IFN-gamma+ and CD3+TNF-alpha+ cells were also significantly higher in the elderly group (p=0.039; p=0.051) respectively. There was no significant difference between the age groups for the percentage or numbers of IL-2-producing CD3+ cells on stimulation. CD3+ cells expressing TNF-alpha were highly associated with CD3+ cells expressing IFN-gamma in both elderly and young people. In contrast, IL-2 secreting CD3+ cells were associated with TNF-alpha and IFN-gamma producing CD3+ cells in young but not elderly subjects providing further evidence for the remodelling of the cytokine network associated with old age. PMID- 11772509 TI - Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. AB - The elderly suffer from an impaired immune function being obvious in a higher susceptibility to infections. Especially the rate of complications after infection with Salmonella, normally confined to the gastrointestinal tract, is raised. We compared in a whole blood assay and in vitro stimulation of peripheral blood mononuclear cell (PBMC) the secretion of interleukin (IL)-1-beta, IL-6, IL 8 and TNF-alpha, after stimulation with lipopolysaccharid (LPS) from Salmonella abortus equi and Escherichia coli, phytohaemagglutinin (PHA) and toxic shock syndrome toxin-1 (TSST-1) by leukocytes of healthy young donors, healthy elderly and healthy elderly fulfilling the SENIEUR protcol. Significantly higher secretion of IL-1-beta, IL-6 and IL-8 after stimulation with LPS were found in the SENIEUR elderly compared to young donors. IL-1-beta, IL-6 and IL-8 were elevated in the whole blood samples of the healthy elderly controls as well. After stimulation of whole blood samples from these healthy elderly with LPS, IL 1 and IL-6 secretion was significantly elevated, but stimulation of their PBMCs showed lower amounts of produced cytokines compared to the PBMCs of healthy young donors. The results suggest that the elvated cytokine releases are caused by an interaction of LPS with a serum factor in the blood of the elderly. Such an overproduction of these inflammatory cytokines by moncytes and neutrophils may be in part responsible for many symptoms elderly people suffer from during an infection with Salmonella. PMID- 11772510 TI - Leukocyte function and life span in a murine model of premature immunosenescence. AB - Aging associates with a decline of physiological functions, including the function of the nervous and the immune system. These aged-related changes occur in various degrees in different members of a mouse outbred population. Accordingly, we have proposed a model of premature immunosenescence in mice, based on the demonstration of premature decline in the behavioral response in a simple T-maze and in several immune functions in Swiss outbred mice. Those mice with a worst (slow) performance in this test (linked to a higher emotional response to stress) show a shorter life span and a decreased immune function when compared to fast mice. In order to provide biomarkers of "biological aging" related to health and survival, the present longitudinal study includes the analysis of several immunological parameters such as, proliferative response to mitogen Con A, NK activity and cytokine (TNFalpha, IL-1beta and IL-2) release by peritoneal leukocytes from female Swiss mice. Slow mice showed a lower proliferative response to Con A, IL-2 and IL-1beta release, an impaired NK activity and an increased TNFalpha production as compared to fast mice. Moreover, the age-associated decline of these functions is more strikingly slow than in fast mice. In summary, we propose the above immunological parameters, that change with aging at a different rate in members of a same population, as useful biomarkers to asses the rate of biological aging in mice. PMID- 11772511 TI - Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients. AB - Cognitive functions display a progressive impairment with ageing, and this is thought to be due to the accumulation of neuronal loss or acute and/or repeated microvascular accidents. Chronic damage to the brain cortex lead to decreasing ability of elderly subjects to cope with daily events and ultimately result in loss of self-sufficiency. Since proinflammatory cytokines have been implicated both in cerebrovascular injury due to atherosclerosis and in Alzheimer's disease (AD), we investigated 70 elderly subjects with neurocognitive and functional impairment. Diagnosis was established in 54, the others were included in the "mixed" group. Sera were collected and stored at -70 degrees C until measurement of IL-1beta and TNF-alpha, performed by commercial ELISA kits. Data obtained were analysed with respect to other socio-demographic, psychoneurological and clinical variables. The results show that serum TNF-alpha was lower in mild-moderate AD compared to severe AD and dementias due to vascular disease, as well as the TNF alpha/IL-1beta ratio. Both cytokines showed a significant relationship with age. Our study suggests that proinflammatory cytokines serum profiles seem to discriminate between mild-moderate AD and vascular or mixed forms of dementia. Furthermore, it offers new evidence of a strong implication of inflammatory mechanisms in atherosclerosis, more than in less severe AD. PMID- 11772512 TI - Human CD4+ T cell clone longevity in tissue culture: lack of influence of donor age or cell origin. AB - CD4+ human T cell clones were derived from activated peripheral blood lymphocytes of healthy young adults to establish cloning efficiencies (CE) and clonal longevities. These results were compared with those obtained using cells from the very elderly, also in excellent health. CE and both maximal and average longevities under appropriate culture conditions were very similar in the two groups. Moreover, CE of CD34+ hematopoietic progenitor cells and longevities of clones derived from them were also similar. Finally, CE and longevities of clones derived from a patient with chronic myelogenous leukaemia were found to be comparable as well. Hence, T cells with absolutely no antigenic exposure in vivo prior to cloning (i.e. CD34-derived) and those potentially exposed to chronic antigenic stimulation (CML-derived) and those from young or old donors all had similar cloning and propagation properties in vitro. These results imply that the longevity of T cells in culture is more likely to be dictated by cloning conditions than any intrinsic differences between the cells studied. PMID- 11772513 TI - Age associated decline in CD25 and CD28 expression correlate with an increased susceptibility to CD95 mediated apoptosis in T cells. AB - Immunosenescence is believed to contribute to increase susceptibility to infectious diseases and cancer in the elderly, and is caused mainly by changes in the T cell compartment. Longitudinal studies were undertaken to examine T cell surface receptor expression and apoptotic susceptibility using Staphylococcal enterotoxin B (SEB) activated human T cells as an in vitro model of an ageing T cell culture. An intracellular stain Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to assess the number of population divisions (PD) occurring in the ageing T cell culture. One major biomarker of aged T cells is a decrease in expression of CD28 and since this is an essential co-stimulatory molecule, its decreasing expression with age could compromise their activation and apoptotic capacity. Activation of T cells resulted in initial up-regulation of CD25, CD95 and CD28, although expression of CD25 and CD28 subsequently decreased with increasing PD. CD4 and CD8 T cells expressed similar CD25 profiles although CD28 expression was unique in each subset. CD4+ cells expressed the highest CD28 levels, and showed a gradual decline in expression with increasing PD, whereas CD8+ cells were low CD28 expressers, but did not appear to lose their expression as they aged. To determine T cell susceptibility to apoptosis via CD95/CD95-L interactions with increasing age, cells were challenged with CD95-L transfected CHO cells at various PD. Increased death was observed as they aged, which correlated with the decreased expression of activation markers CD25 and CD28. PMID- 11772514 TI - A model for the phenotypic presentation of Werner's syndrome. AB - Werner's syndrome (WS) is a valuable model of accelerated ageing and results from mutations in a recQ helicase (wrn). WS fibroblasts show a mutator phenotype, replication fork stalling, increased rates of mean telomeric loss and accelerated cellular senescence. Senescence has been proposed as a candidate mechanism for the ageing of mitotic tissue. However, some mitotic tissues (such as the immune system) seem unaffected in WS. Is this evidence against a role for cell senescence in ageing? Two experiments resolve this paradox (i) the demonstration that the abbreviated replicative lifespan of WS fibroblasts can be corrected by the ectopic expression of telomerase and (ii) the demonstration that T cells derived from WS patients have the mutator phenotype characteristic of the disease but show no reduction in replicative potential. Since T cells can upregulate telomerase naturally these findings are consistent with a model in which the only wrn-mediated deletions that have a significant effect on replicative lifespan are those at or near the telomere. These data are thus supportive of a role for senescence in the ageing of the immune system. Emerging data on divisional counting mechanisms have the potential to produce many other apparent WS "paradoxes". Accordingly, we propose a general model for the phenotypic presentation of WS, which includes a modification of the Olovnikov model of telomere erosion. Somewhat unexpectedly, this predicts that accelerated senescence should not be observed in all telomerase-negative WS cell types. PMID- 11772515 TI - Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream signaling molecules. AB - Tumor necrosis factor-alpha (TNF-alpha) induces apoptosis predominantly via TNF receptor I (TNF-RI). We have examined the molecular and biochemical pathways of TNF-alpha-induced apoptosis in T cells from aged and young subjects. Aged subjects show absolute lymphopenia and decreased numbers of both CD4+ and CD8+ T cells. T cells from aged subjects show increased sensitivity to TNF-alpha-induced apoptosis that is associated with increased expression of TNF-RI and decreased expression of TNF-RII in both CD4+ and CD8+ T cells. Agonistic TNF-RI also induced greater apoptosis in T cells from aged subjects as compared to young subjects, suggesting that increased TNF-alpha-induced apoptosis in aging is predominantly mediated via TNF-RI. There was an increased expression of FADD and increased activation of caspase 8 and caspase 3 in lymphocytes from aged humans as compared to young subjects. A role of impaired TNF-RII-mediated signaling in increased apoptosis in aged subjects is also discussed. PMID- 11772516 TI - Age dependent impact of LMP polymorphisms on TNFalpha-induced apoptosis in human peripheral blood mononuclear cells. AB - As a consequence of inflammatory stimuli (such as TNFalpha and IFNgamma), some constitutive subunits of the proteasome, the principal mediator of nonlysosomal protein degradation, are replaced with other subunits, the large multifunctional proteases LMP2 and LMP7, thus originating the immunoproteasome. An age-related alteration of proteasome activity and susceptibility to TNFalpha-induced apoptosis, in which LMP2 and the nuclear factor (NF)-kappaB activation play an important role has been recently reported. In this paper, we investigated the possible influence of two LMP2 and LMP7 polymorphisms on susceptibility to TNFalpha-induced apoptosis. Our data show that an increase in susceptibility to TNFalpha-induced apoptosis is evident in long-lived people (aged >88 years) in comparison to young individuals. Moreover, the modulation of LMP2 codon 60 polymorphism on TNFalpha-induced apoptosis is evident in long-lived subjects. Genotyping of 311 young people and 157 nonagenarians and centenarians revealed no changes in LMP2 codon 60 genotype frequency distribution. No correlation with TNFalpha-induced apoptosis and no difference in frequency between young people and nonagenarians/centenarians was observed when the LMP7 nucleotide 145 polymorphism was studied. PMID- 11772517 TI - The -174 C/G locus affects in vitro/in vivo IL-6 production during aging. AB - IL-6 in vitro production, as well as the serum/plasma concentration of the cytokine, increase with age. In the present investigation, a total of 62 individuals (31 males and 31 females), aged from 29 to 93 years of age (mean age of males: 60.4 years; mean age of females: 59.4 years) were assessed for IL-6 plasma concentration, and for IL-6 in vitro production, using supernatants of 4h cultured adherent peripheral blood mononuclear cells (aPBMC). The subjects were examined for a C to G transition at nucleotide -174 of the IL-6 gene promoter ( 174 C/G locus), and were classified as C allele carriers (C+) or non-carriers (C ). We found that: (i) aPBMC from C+ individuals produced smaller amounts of IL-6 in vitro than C- individuals; (ii) IL-6 production by aPBMC increased with age in C+ but not in C- subjects; (iii) there was no correlation between IL-6 plasma levels and in vitro IL-6 production by aPBMC; (iv) IL-6 C+ individuals had lower plasma levels than C- individuals, and this phenomenon was significant only in men. On the whole our data indicate that the production of IL-6 is genetically controlled and age- and gender-dependent. PMID- 11772518 TI - Allele frequencies of +874T-->A single nucleotide polymorphism at the first intron of interferon-gamma gene in a group of Italian centenarians. AB - Ageing is characterized by a pro-inflammatory status which could contribute to the onset of major age-related diseases such as cardiovascular diseases, neurodegeneration, osteoarthritis and osteoporosis, and diabetes. Thus, it can be hypothesized that genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. We have studied the distribution of +874T-->A interferon-gamma (IFN-gamma) polymorphisms in a large number of Italian centenarians to evaluate if the two alleles might be differently represented in people selected for longevity. DNA samples were obtained from 174 Italian centenarians (>99 years old, 142 women and 32 men) and from 248 <60-year-old control subjects (90 women and 158 men) matched for geographical distribution. Polymorphisms at +874 were identified by using amplification refractory mutational system methodology. The +874T allele was found less frequently in centenarian women than in centenarian men or in control women whereas no significant differences were observed in the distribution of the two alleles between male or female controls. Allele frequencies in centenarian men were not found significantly different from male controls. Possession of the +874A allele, known to be associated with low IFN-gamma production, significantly increases the possibility to achieve extended longevity, suggesting that the pro-inflammatory status characteristic of ageing may be detrimental for successful ageing. The datum that the allele was significantly increased in female but not male centenarians seems to strengthen the idea that gender may be a major variable in the biology of the ageing process. However, the present data add another piece of evidence to the complex puzzle of genetic and environmental factors involved in controlling life span expectancy in humans. Thus, studies on cytokine gene polymorphisms may promise to individuate a complex network of trans-interactive genes able to influence the type and strength of responses to environmental stressors and as a final result, thereby conditioning individual life expectancy. PMID- 11772519 TI - The DNA repair protein ku is involved in gp130-mediated signal transduction events in PBMC from young but not from elderly subjects. AB - Ku, composed of 70kDa (ku 70) and 86kDa (ku 80) proteins, is the DNA-targeting subunit of the DNA-dependent serine/threonine kinase (DNA-PK), which plays a crucial role in DNA double strand break recognition and repair in mammalian cells. We have investigated the effects of an IL-6-type cytokine (K-7/D-6), known to trigger gp130, on the expression and function of the ku protein in cytoplasmic and nuclear extracts of freshly isolated human peripheral blood mononuclear cells (PBMC) from subjects of different ages. DNA-binding of nuclear ku was found to be increased by cytokine treatment of cells from young donors but only to a negligible extent from elderly subjects. This cytokine effect was correlated with a greater amount of phosphorylated ku 80, rather than increased expression of ku 70 and ku 80 proteins. DNA-binding activity of cytoplasmic ku was hardly discernible, as compared to nuclear ku, in both young and elderly subjects and was unaffected by the cytokine treatment regardless of age. Regarding the mechanisms whereby ku and gp130 signaling are coupled in PBMC, results from co immunoprecipitation experiments have shown that ku in the cytoplasm of PBMC from young, but not from elderly subjects, is associated with Tyk-2, a kinase involved in signal transduction events after gp130 triggering by IL-6-type cytokines. This association was independent of PHA stimulation. Moreover, the present results indicate that after gp130 signaling both Tyk-2 and ku 80 are phosphorylated, suggesting their activation by K-7/D-6. PMID- 11772520 TI - Mitochondrial DNA damage in lymphocytes: a role in immunosenescence? AB - An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA(4977) and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA(4977) and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA(4977) was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence. PMID- 11772521 TI - The effect of the histone deacetylase inhibitor, trichostatin A, on total histone synthesis, H1(0) synthesis and histone H4 acetylation in peripheral blood lymphocytes increases as a function of increasing age: a model study. AB - A pilot study was initiated in order to ascertain whether the age of the donor might affect either the induction of the expression of H1(0) or histone H4 acetylation by the very specific histone deacetylase inhibitor, trichostatin A. This was investigated in a cell system which normally does not express this linker histone variant, i.e. peripheral blood lymphocytes (PBL), which were obtained from donors of different ages (25-95 years). Forty-eight hours after activation by the mitogen phytohemaglutinin (PHA), 250 ng of trichostatin A per 10(6) cells per ml culture medium was added and cultured for an additional 24h. Assays were performed 72 h after initiation of cultures, i.e. during the S phase. It was found that in PBL, trichostatin A induced the expression of the linker histone variant, H1(0) as well as histone H4 acetylation, and, more importantly, that these effects were enhanced with increasing age of the donor. More specifically, under the influence of trichostatin A, PBL showed increasing H1(0) synthesis rates and increasing levels of histone H4 acetylation as a function of increasing age of the donor. Moreover, although trichostatin A induced an increasing expression of H1(0) with increasing age, it also concomitantly partially inhibited S phase total histone synthesis. This inhibition also increased as a function of increasing age of the donor. PMID- 11772522 TI - MtmRNA gene expression, via IL-6 and glucocorticoids, as potential genetic marker of immunosenescence: lessons from very old mice and humans. AB - Metallothioneins (MTs) are involved in metal-related cell homeostasis because of their high affinity for metals forming clusters. The main functional role of MTs is to sequester and/or dispense zinc participating in zinc homeostasis, which is relevant in normal immune response. Consistent with this role, MTs gene expression (MTmRNA) is transcriptionally induced by a variety of stressing agents to protect cells from reactive oxygen species. In order to accomplish this task, MTs gene expression is affected by glucocorticoids and IL-6 for a prompt immune response. This protection is peculiar in young-adult age during transient stress and inflammatory condition, but not in ageing because stress-like condition and inflammation are constant for the whole circadian cycle. This may lead MTs to turn-off from role of protection in young age to deleterious one in ageing. The aim is to suggest MTmRNA as potential genetic marker of immunosenescence. Liver MTmRNA, IL-6 and glucocorticoids levels are high, whereas the bioavailability of zinc ions is low and natural killer cells activity is depressed in old and very old mice during the light period as compared to young in the same period. An inversion of nutritional-endocrine-immune profile exclusively occurs in young mice during the night showing the existence of immune plasticity. No inversion occurs in old mice during the night. As a consequence, no immune plasticity in old mice ensues. By contrast, very old mice remodel the altered MTmRNA and immune endocrine profile during the night up to values of young ones observed during the light period. Therefore, the remodelling of MTmRNA may be involved in the maintenance of immune plasticity with subsequent successful ageing. Thus, MTmRNA, via IL-6 and glucocorticoids, may be potential genetic marker of immunosenescence. This assumption is reinforced by low MTmRNA in lymphocytes of nonagenarians and young-adult people in comparison with elderly and Down's syndrome subjects. PMID- 11772523 TI - Ubiquitin-proteasome pathway is compromised in CD45RO+ and CD45RA+ T lymphocyte subsets during aging. AB - Recent reports from our laboratory have demonstrated that CD45RO+ and CD45RA+ T lymphocytes from the elderly are compromised in their response to activation induced IL-2 receptor expression, IkappaB-alpha degradation, as well as nuclear translocation of NFkB. To understand the basis of this activation-induced dysfunction in the elderly, we have examined the role of the ubiquitin-proteasome pathway. Our results demonstrate that both CD45RO+ and CD45RA+ T lymphocytes from the elderly show significant reduction in the constitutive 26S proteasome associated chymotryptic activity, when compared to those in the young. Additionally, anti-CD3-CD28 treatment induced enhancement of proteasome associated enzymatic activity in cells from the young, but not in cells from the elderly. Lowered proteasome-associated activity and its effect on reduced immune responses in the elderly could be mimicked by experiments which involved pretreatment of T cells from young donors with a proteasome specific inhibitor, lactacystin. These data demonstrate that IL-2 receptor induction is clearly compromised in T cells from the young when proteasomes are inhibited by pretreatment with lactacystin. An examination of ubiquitin specific hydrolase activity, demonstrated a decrease in activated CD45RA+ and CD45RO+ T cell subsets from the elderly when compared to young. These results suggest that lowered proteasome-associated enzymatic activity in combination with compromised de ubiquitinating activity may be responsible for lowered activation-induced NFkB and NFkB-mediated gene expression in elderly subjects. PMID- 11772524 TI - Modulation of human lymphocyte proliferative response with aging. AB - Previously, we have demonstrated age-associated alterations in transmembrane signaling. One of the most reproducible alterations found in the immune response with aging is the decrease of lymphocyte proliferation on stimulation with various different mitogens. Here, we confirm that proliferative responses to stimulation with phytohaemagglutin (PHA), recombinant human IL-2, or anti-CD3 monoclonal antibody are all greater in the young (20-25 years) than old (60-87 years) population. We attempted to modulate the proliferative response using various agents acting at different levels of transmembrane signaling (pertussis toxin, cholera toxin, isoproterenol, PMA, Ca ionophore A23187), as well as at the level of the lymphocyte plasma membrane (methyl-beta-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or C). None of these agents was able to restore effectively the proliferative response of lymphocytes from the aged to the level of young subjects. Even the combination of A23187 and PMA acting directly on calcium metabolism and protein kinase C activity was insufficient to restore the decreased mitogenic capacity of T cells from elderly subjects. Cyclodextrin, which decreases the cholesterol content of the membrane, increased the proliferative response of lymphocytes of elderly subjects, but not to the level of the young. Vitamin E had a very strong inhibitory effect on lymphocyte stimulation in both the age groups, except in combination with MBCD in T cells of the elderly, while Vitamin C had no significant modulatory effect. MAPK ERK and p38 activation was found to be decreased with aging in T cells after anti-CD3 mAb stimulation. Vitamin E but not Vitamin C strongly inhibited MAPK ERK or p38 activation. The direct activation of certain molecules or the modulation of the cholesterol content of the membrane seems to be effective immunomodulatory interventions with aging. PMID- 11772525 TI - Immunosenescence of macrophages: reduced MHC class II gene expression. AB - In order to determine the effect of aging on macrophages, we produced bone marrow derived macrophages in vitro from young and aged mice. We analyzed the effect of aging on the genomic expression of macrophages in these conditions, without the influence of other cell types that may be affected by aging. Macrophages from young and aged mice were present in similar numbers and showed an identical degree of differentiation, cell size, DNA content and cell surface markers. After incubation with interferon-gamma (IFN-gamma), the expression at the cell surface of the MHC class II gene IA complex product and the levels of intracellular IAbeta protein and mRNA were lower in aged macrophages. Moreover, the transcription of IAbeta gene was impaired in aged macrophages. The amount of transcription factors that bound to the W and X boxes, but not to the Y box of the IAbeta promoter gene were lower in aged macrophages. Similar levels of CIITA mRNA were found after IFN-gamma treatment of both young and aged macrophages. This shows that neither the initial cascade that starts after the interaction of IFN-gamma with the receptor, nor the second signals involved in the expression of CIITA, are impaired in aged macrophages. These data could explain, at least in part, the impaired immune response associated to senescence. PMID- 11772526 TI - Modulation of superoxide anion levels of macrophages from young-adult and old mice by the norepinephrine metabolite, 4-hydroxy-3-methoxyphenyl-glycol. AB - It is well known that a bidirectional relation exists between the immune and the classic animal regulation systems, the nervous and endocrine systems. It has also been reported that ageing has a negative effect on neuro-immuno-endocrine integration. Since it has been shown that norepinephrine (NE) differently modulates the phagocytic process of macrophages from young or old mice, and considering that NE has a short lifetime, the aim of this study is to evaluate the possible immunomodulatory role of the NE end-metabolite, 4-hydroxy-3 methoxyphenyl-glycol (HMP-glycol), on the superoxide anion levels of peritoneal macrophages from young-adult (22+/-2 weeks) and old (72+/-2 weeks) BALB/c mice. Macrophages were incubated with HMP-glycol in a range of concentrations between 10(-12) and 10(-3)M, and superoxide anion levels (both extracellular and intracellular) were evaluated by using the NBT reduction test. The response of macrophages to HMP-glycol was different between young-adult and old animals. While all concentrations (10(-12), 10(-9), 10(-7), 10(-5), 10(-3)M) of HMP-glycol led to lower extracellular O(-)(2) levels (p<0.05) in macrophages from young adult mice, only the 10(-3)M concentration of HMP-glycol led to a significant decrease in the extracellular O(-)(2) production in macrophages from old mice. No significant changes were found in the intracellular O(2)(-) levels when macrophages were incubated with the different concentrations of HMP-glycol in either young-adult or old mice. Thus, the modulation of macrophage function by NE not only depends on their concentration, but also on the products of NE catabolism. The effect of NE metabolite will also depend on the age of the animals as there is an age-dependent decreased capacity to respond to low concentrations of HMP-glycol. PMID- 11772527 TI - Alpha-lipoic acid modulates NF-kappaB activity in human monocytic cells by direct interaction with DNA. AB - The constitutive activity of the redox-sensitive transcription factor, NF-kappaB, which regulates the production of many inflammatory cytokines and adhesion molecules, appears to be up-regulated in an age-associated manner and it is thought this might contribute to the increased incidence of chronic inflammatory conditions observed with increasing age. As some antioxidants have demonstrated protective effects against rheumatoid arthritis, we are investigating the effects of vitamin E, vitamin C and alpha-lipoic acid (ALA) on NF-kappaB activity and on the expression of intracellular adhesion molecule (ICAM)-1. MonoMac6 cells (a human monocytic cell line) stimulated with tumour necrosis factor-alpha (TNF alpha) were treated with antioxidants at physiological achievable levels and ICAM 1 mRNA levels investigated. Both vitamin E and vitamin C had no effect on ICAM-1 expression at the doses used, but ALA reduced the TNF-alpha-stimulated ICAM-1 expression in a dose-dependent manner, to levels observed in unstimulated cells. Alpha-lipoic acid also reduced NF-kappaB activity in these cells in a dose dependent manner. Addition of ALA to the binding reaction of nuclear extract with DNA prior to gel-shift analysis showed that it caused inhibition at this level. These initial results suggest that antioxidant modulation of monocyte activity might have potential benefits in inhibiting the dysregulated activity of redox sensitive transcription factors that occurs with increasing age. PMID- 11772528 TI - Differential expression of various cytokine receptors in the brain after stimulation with LPS in young and old mice. AB - The effect of lipopolysaccharides (LPS) on the expression of cytokine receptors was examined in the spleen, brain and pituitary gland, and compared in young and old mice. The level of mRNA for various cytokine receptors (IL-1RI, IL-2Ralpha, IL-3Ralpha, IL-6R, TNFalphaR and IFNgammaR) was found to be increased in the spleen of young but not in old mice within 2-6h of stimulation with LPS. Similar enhancement of cytokine receptor mRNA was also observed in the brain after LPS stimulation, but the magnitude varied according to the type of cytokine receptor, the site of brain and the age of the mice. In the hypothalamus, the level of mRNA for IL-1R, IL-3R, IL-6R and IFNgammaR increased in young but not in old mice. Reciprocally, in the cerebral cortex, mRNA for TNFalphaR and IFNgammaR increased in old but not in young mice. In the hippocampus, TNFalphaR mRNA expression, increased in young but not in old mice, and expression of the other cytokine receptors did not change greatly in either. In the pituitary gland, mRNA for IL 6R, TNFalphaR and IFNgammaR increased in both young and old mice, but IL-2Ralpha increased only in young mice.Thus, various cytokines produced by immune cells might directly or indirectly influence brain functions through the various cytokine receptors expressed in the brain. Moreover, interactions between the immune system and the brain at the time of infection would be expected to be different in young and old mice, because cytokine production changes with age, as does the expression of their receptors in the brain. PMID- 11772529 TI - Melatonin and aging: in vitro effect of young and mature ring dove physiological concentrations of melatonin on the phagocytic function of heterophils from old ring dove. AB - We have studied the circadian rhythm of melatonin in the ring dove (Streptopelia risoria) for different age groups: young (1-1.5 years), mature (3-4 years) and old animals (>8 years). Melatonin levels were determined by radioimmunoassay. Results showed a significant decline in plasma melatonin levels in old animals when compared with the concentrations observed in the other two age groups, in which maximum (nocturnal) concentrations were 300 pg/ml and minimum (diurnal) concentrations were 50 pg/ml. We analyzed the in vitro effect of the physiological concentrations found in young and mature animals on the heterophils obtained from old animals, evaluating the capacity for ingestion and destruction of Candida albicans, and the oxidative metabolism associate to phagocytosis by determining the superoxide anion levels. Melatonin induced an increase in both the phagocytosis index and the candidicide capacity. This effect was dose dependent. In relation with the oxidative metabolism, a decline in superoxide anion levels after incubation with both concentrations of the hormone was observed. Thus our results corroborate in this avian species the decline in plasma melatonin levels with advanced age, as well as the enhancing effect of physiological concentrations of melatonin on the phagocytic function. PMID- 11772530 TI - Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly. AB - While influenza immunization significantly reduces the risk of pneumonia and associated deaths, vaccination of elderly only affords 30-50% protection against influenza disease. The purpose of this study was to: (1) evaluate the consistency of immune responses across multiple years in young and elderly; (2) determine the contribution of antibody and cell-mediated responses in protection after immunization with influenza vaccine. Independently living healthy elderly (>200/year; mean age 78.8-80.6/year) were recruited yearly in this four year study. The results clearly demonstrate: (1) both young and elderly consistently produced significant antibody and T cell proliferative responses to influenza vaccine upon yearly immunization; however, both responses of elderly were significantly and consistently lower than young. (2) Percentages of both young and elderly demonstrating protective titers (i.e. HI>/=40) increased post immunization each year, but were consistently higher in young compared to elderly. (3) The risk of developing influenza disease after immunization was highest among elderly demonstrating neither antibody nor cell-mediated responses. Importantly, the risk of influenza disease was comparable in elderly demonstrating a cell-mediated response alone, an antibody response alone, or both cell-mediated and antibody responses. This suggests that cell-mediated responses play a significant role in protection in at least a subset of elderly from influenza disease after immunization. PMID- 11772531 TI - Clinical features of late onset psoriatic arthritis. AB - The aim of this work is to compare the clinical and radiological manifestations of patients presenting late onset psoriatic arthritis (PsA) with early onset PsA. An overall of 96 consecutive PsA patients were studied over an 8-month-period. Clinical, laboratory and radiographic signs were assessed. Of the 96 patients studied, 84 had their earliest symptoms before the age of 60 (Group I) and 12 after it (Group II). In Group II the mean age was 65.7 years (range 60-73), the sex ratio (male/female) was 9/3. All patients were HLA-B27 negative; the clinical forms observed were: polyarticular (6 patients; 50%), oligoarticular (4 patients; 33%) and spondyloarthropathy (SpA) (2 patients; 17%). Only two patients had asymmetric sacroiliitis and three had history of dactylitis episodes. In conclusion, we found distinct clinical manifestations in late onset PsA. Peripheral affection was found predominant. The male/female ratio was higher than other age groups. PMID- 11772532 TI - Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. AB - Results from a previous longitudinal study, the Swedish OCTO-Immune study, indicated that the combination of higher CD8 peripheral blood lymphocytes (PBLs), decreased CD4 PBLs, and poor proliferative response to mitogenic stimulation in very old humans were associated with an increased 2 year mortality. In follow up studies this combination of immune parameters was significantly associated with a CD4/CD8 ratio less than one and positive IgG serologic titers to cytomegalovirus (CMV). The present study, the Swedish NONA-Immune study, was an extension of that study, using a new sample of the very old. The results of this study confirmed the results of the previous study and extended the surface marker profile of the PBLs, indicating that the CD4/CD8 ratio change is associated with increased CD8 cells, decreased CD4 cells, and lymphocyte activation. The predominant phenotypes of the CD3+CD8+ cells were CD27-, CD28-, CD56+, and CD57+, CD45RA+, and double marked CD45RA+RO+. As in the OCTO study, the NONA-Immune data indicated that the changes are associated significantly with seropositive responses to CMV. PMID- 11772533 TI - Age-associated thymic atrophy is linked to a decline in IL-7 production. AB - Age-associated thymic atrophy results in a decline in T lymphocyte output and has been identified as one of the key events that precede inefficient functioning of the immune system in later life. Thymic atrophy is thought to result from a failure of the thymic microenvironment to support thymopoiesis in old age and recent evidence suggests that a decline in interleukin-7 (IL-7) expression may limit thymocyte development by restricting combinations of survival, proliferation and rearrangement of the TCRbeta chain. Using RT-PCR and the RNase protection assay, we show that the expression of IL-7 declines with age. Analysis of Connexin 43 expression, a component molecule of gap junctions, whose function is to connect epithelial cells, does not markedly decline with age. These observations suggest that a decline in IL-7 expression is not matched by a similar loss of epithelial cells. These results in conjunction with other studies lead us to speculate that IL-7 producing MHC class II positive TECs are being replaced by cells that do not have this capacity. PMID- 11772534 TI - Nonagenarians from the Swedish NONA Immune Study have increased plasma antioxidant capacity and similar levels of DNA damage in peripheral blood mononuclear cells compared to younger control subjects. AB - The results of previous work from our laboratories have suggested that free radical damage to T cells as they age may contribute to the age-related decline in the T cell-mediated immune response. The aims of this investigation were to assess the efficiency of in vivo antioxidant capacity through determining the antioxidant capacity of plasma using the ferric reducing ability of plasma assay, and to assess the levels and types of DNA damage (as a measure of in vivo antioxidant efficiency) using the alkaline comet assay and two enzymatic modifications of the comet assay, in peripheral blood mononuclear cells (PBMCs) from nonagenarian subjects drawn from the Swedish NONA Immune Study. The results obtained were compared with those from middle-aged (40-60 years) controls to identify potential anti-immunosenescent effects of in vivo antioxidants. The results revealed a significantly higher plasma antioxidant capacity in NONA subjects compared to controls, and these results support a relationship between longevity and intact immune function, which may be underpinned by antioxidant defences which reduce free radical damage to PBMC, thus helping to maintain cell function. The NONA subjects were found to have similar levels of DNA damage in their PBMCs to those found in middle aged controls. PMID- 11772539 TI - Endogenous and exogenous interferons in HIV-infection. AB - The interferons (IFNs) belong to the body's natural defensive response mechanisms directed against virus infections including also the human immunodeficiency virus (HIV) infection. This review discusses the current knowledge concerning the role of IFNs types I and II during the HIV infection. The author analyzes the HIV driven process of endogenous IFNs induction in different cell types as well as the development of unusual acid-labile IFN following the HIV infection, its nature and clinical significance. Possible action mechanisms of different exogenous IFN types against the HIV-infection are reviewed taking into consideration the stages of HIV replication accompanied by these mechanisms of action and describing both positive and negative roles of IFNs during this disease. The author discusses also some well-known IFN-inducible antiviral pathways participating in the anti-HIV mechanisms and enzymes realizing antiviral action (PKR, 2'5'-OAS, iNOS, IDO, Mx and 9-27 proteins). A problem of HIV defense against the anti-HIV IFN action as well as some aspects of HIV-accelerating IFN effects are also examined in detail. PMID- 11772540 TI - In vivo assessment of colon microcirculation: comparison of the new OPS imaging technique with intravital microscopy. AB - BACKGROUND: The Orthogonal Polarization Spectral (OPS) imaging technique has been introduced for in vivo assessment of microcirculation in humans. Unclear remains, whether the new technique would allow for accurate investigations of the colon microcirculation with respect to the unique conditions of the microvasculature in that particular tissue. Therefore, the aim of this study was to validate the new technique against intravital fluorescence microscopy (IFM) for the visualization of colon microcirculation in a murine model of inflammatory bowel disease (IBD). METHOD: IBD was induced in Balb/c mice by dextran sulfate sodium (DSS), controls received normal water. In each animal, both the CYTO-SCAN A/R and IFM were used to image the microcirculation (n = 7 in each group). Postcapillary venular diameter, venular red blood cell velocity (RBC-V) and functional capillary density (FCD) were analyzed on the colon muscularis and mucosa and compared to each other using linear regression analysis and Bland-Altman plots. RESULTS: All parameters correlated significantly between the both methods. The venular diameters and the RBC-V were significantly different between control and colitis group in contrast to FCD; these results were present while using both methods. CONCLUSION: Our study demonstrates that the new technique for visualization of microcirculation without use of fluorescent dyes, the OPS-imaging, allows for quantitative measurement of the key microcirculatory parameters of the mouse colon. PMID- 11772541 TI - Hepatotoxic reactions induced by beta-lactamase inhibitors. AB - Since amoxicillin/clavulanate was first introduced in the UK in 1981, beta lactamase inhibitors are used increasingly worldwide. Two more drugs of this class are currently available, sulbactam and tazobactam. Meanwhile, adverse drug reactions associated with amoxicillin/clavulanate occurring late after the end of therapy have been repeatedly published. In many cases, a cholestatic hepatitis was diagnosed that was most likely caused by the clavulanic acid component of the combination. Symptoms were mostly mild and reversible, whereas a number of cases showing a protracted, even fatal course of the disease have been documented. This article summarizes and analyzes all relevant studies and case reports dealing with hepatotoxicity caused by beta-lactamase inhibitors. The description of a typical case from our own patient population illustrates the clinical challenge associated with this adverse drug reaction. PMID- 11772542 TI - Does ketamine/propofol anesthesia possess antiarrhythmogenic quality? A perioperative study in aortocoronary bypass patients. AB - We compared ketamine/propofol (KP) anesthesia with the commonly used high dose fentanyl (F) anesthesia in patients who underwent aortocoronary bypass surgery. The doses of anesthetic drugs and their time schedule of administering was standardized. The study period included the postoperative ICU stay. 31 patients were enrolled (15 in the KP- and 16 in the F-group). The measured and calculated hemodynamic data were intra- and postoperative not statistically different,except the mean and systolic arterial pressure (p = 0.049), which were in the KP-group from the first postoperative hour higher. After separation from bypass the F patients were more dependent of adrenoreceptor agonists for hemodynamic stabilization than the KP-patients. The postoperative Holter ECG monitoring resulted in following issues: ventricular tachycardias, ventricular salvos and ventricular couplets were significantly less to observe in the KP-group. A difference existed also in the frequency of ventricular extrasystoles, but without statistical significance. No patient fulfilled all criteria for a perioperative myocardial infarction, although in some patients one or two pathologic enzyme value or a pathologic change in the postoperative ECG could be proved. Ketamine resembles in the chemical structure cocaine, therefore it shares with cocaine some effects: inhibiting the neuronal uptake of catecholamines and acting as a sodium-channel blocker. Inhibiting the sodium current is one of the kinds how antiarrhythmic drugs work. CONCLUSION: The study indicates that the use of ketamine for anesthesia and perioperative sedation coincidences with fewer ventricular rhythm disturbances than with opioid and benzodiazepine as anesthetic and sedation agents. PMID- 11772544 TI - Commentary on the "Review of Internet Health Information Quality Initiatives". PMID- 11772543 TI - Review of internet health information quality initiatives. AB - BACKGROUND: The massive growth of health information on the Internet; the global nature of the Internet; the seismic shift taking place in the relationships of various actors in this arena, and the absence of real protection from harm for citizens who use the Internet for health purposes are seen to be real problems. One response to many of these problems has been the burgeoning output of codes of conduct by numerous organizations trying to address quality of health information. OBJECTIVES: Review the major self-regulatory initiatives in the English-speaking world to develop quality and ethical standards for health information on the Internet. Compare and analyze the approaches taken by the different initiatives. Clarify the issues around the development and enforcement of standards. METHODS: Quality initiatives selected meet one or more of the following criteria: Self-regulatory. A reasonable constituency. Diversity (eg, of philosophy, approach and process)-to achieve balance and wide representation, and to illustrate and compare different approaches. Historic value. A wider reach than a national audience, except when its reach is a significant sector of the Internet health information industry. The initiatives were compared in 3 ways: (1) Analysis and comparison of: key concepts, mechanism, or approach. Analysis of: the obligations that a provider has to meet to comply with the given initiative, the intended beneficiaries of that initiative, and the burdens imposed on different actors. These burdens are described in terms of their effect on the long-term sustainability and maintenance of the initiative by its developers. Analysis of the enforcement mechanisms. (2) Analysis and comparison by type of sponsoring organization, the reach of the initiative, and the sources of funding of the initiative or the sponsoring organization. (3) How the various initiatives fall under 1 of 3 key mechanisms and comparison of the advantages and disadvantages of these key mechanisms. RESULTS: The issues that affect the initiatives and future work on the quality of health information on the Internet are identified and analyzed. These issues are: (a) Three key mechanisms used in the quality initiatives (b) Sustainability issues that affect the initiatives: Burdens placed on health information providers, citizens and others. Currency and maintenance issues of the initiatives. Funding. Cost. Acceptance. Market conditions. User indifference or ambivalence. (c) Enforcement issues surrounding the initiatives (d) Adequacy of approach, scope, reach, and enforcement provisions of the various quality initiatives (e) Gaps that need to be addressed to achieve good quality of health information on the internet CONCLUSIONS: Ten conclusions are presented. A framework of action to be undertaken by the World Health Organization in the field of quality of health information on the Internet is recommended. PMID- 11772545 TI - Evaluation of Norwegian cancer hospitals web sites and explorative survey among cancer patients on their use of the internet. AB - BACKGROUND: Hospital homepages should provide comprehensive information on the hospital's services, such as departments and treatments available, prices, waiting time, leisure facilities, and other information important for patients and their relatives. Norway, with its population of approximately 4.3 million, ranks among the top countries globally for its ability to absorb and use technology. It is unclear to what degree Norwegian hospitals and patients use the Internet for information about health services. OBJECTIVES: This study was undertaken to evaluate the quality of the biggest Norwegian cancer hospitals Web sites and to gather some preliminary data on patients use of the Internet. METHODS: In January 2001, we analyzed Web sites of 5 of the 7 biggest Norwegian hospitals treating cancer patients using a scoring system. The scoring instrument was based on recommendations developed by the Norwegian Central Information Service for Web sites and reflects the scope and depth of service information offered on hospital Web pages. In addition, 31 cancer patients visiting one hospital-based medical oncologist were surveyed about their use of the Internet. RESULTS: Of the 7 hospitals, 5 had a Web site. The Web sites differed markedly in quality. Types of information included - and number of Web sites that included each type of information - were, for example: search option, 1; interpreter service, 2; date of last update, 2; postal address, phone number, and e-mail service, 3; information in English, 2. None of the Web sites included information on waiting time or prices. Of the 31 patients surveyed, 12 had personal experience using the Internet and 4 had searched for medical information. The Internet users were significantly younger (mean age 47.8 years, range 28.4-66.8 years) than the nonusers (mean age 61.8 years, range 33.1-90.0 years) (P = 0.007). CONCLUSIONS: The hospitals Web sites offer cancer patients and relatives useful information, but the Web sites were not impressive. PMID- 11772546 TI - Use of the internet as a resource for consumer health information: results of the second osteopathic survey of health care in America (OSTEOSURV-II). AB - BACKGROUND: The Internet offers consumers unparalleled opportunities to acquire health information. The emergence of the Internet, rather than more-traditional sources, for obtaining health information is worthy of ongoing surveillance, including identification of the factors associated with using the Internet for this purpose. OBJECTIVES: To measure the prevalence of Internet use as a mechanism for obtaining health information in the United States; to compare such Internet use with newspapers or magazines, radio, and television; and to identify sociodemographic factors associated with using the Internet for acquiring health information. METHODS: Data were acquired from the Second Osteopathic Survey of Health Care in America (OSTEOSURV-II), a national telephone survey using random digit dialing within the United States during 2000. The target population consisted of adult, noninstitutionalized, household members. As part of the survey, data were collected on: facility with the Internet, sources of health information, and sociodemographic characteristics. Multivariate analysis was used to identify factors associated with acquiring health information on the Internet. RESULTS: A total of 499 (64% response rate) respondents participated in the survey. With the exception of an overrepresentation of women (66%), respondents were generally similar to national referents. Fifty percent of respondents either strongly agreed or agreed that they felt comfortable using the Internet as a health information resource. The prevalence rates of using the health information sources were: newspapers or magazines, 69%; radio, 30%; television, 56%; and the Internet, 32%. After adjusting for potential confounders, older respondents were more likely than younger respondents to use newspapers or magazines and television to acquire health information, but less likely to use the Internet. Higher education was associated with greater use of newspapers or magazines and the Internet as health information sources. Internet use was lower in rural than urban or suburban areas. CONCLUSIONS: The Internet has already surpassed radio as a source of health information but still lags substantially behind print media and television. Significant barriers to acquiring health information on the Internet remain among persons 60 years of age or older, those with 12 or fewer years of education, and those residing in rural areas. Stronger efforts are needed to ensure access to and facility with the Internet among all segments of the population. This includes user-friendly access for older persons with visual or other functional impairments, providing low-literacy Web sites, and expanding Internet infrastructure to reach all areas of the United States. PMID- 11772547 TI - Design and implementation of a portal for the medical equipment market: MEDICOM. AB - BACKGROUND: The MEDICOM (Medical Products Electronic Commerce) Portal provides the electronic means for medical-equipment manufacturers to communicate online with their customers while supporting the Purchasing Process and Post Market Surveillance. The Portal offers a powerful Internet-based search tool for finding medical products and manufacturers. Its main advantage is the fast, reliable and up-to-date retrieval of information while eliminating all unrelated content that a general-purpose search engine would retrieve. The Universal Medical Device Nomenclature System (UMDNS) registers all products. The Portal accepts end-user requests and generates a list of results containing text descriptions of devices, UMDNS attribute values, and links to manufacturer Web pages and online catalogues for access to more-detailed information. Device short descriptions are provided by the corresponding manufacturer. The Portal offers technical support for integration of the manufacturers Web sites with itself. The network of the Portal and the connected manufacturers sites is called the MEDICOM system. OBJECTIVES: To establish an environment hosting all the interactions of consumers (health care organizations and professionals) and providers (manufacturers, distributors, and resellers of medical devices). METHODS: The Portal provides the end-user interface, implements system management, and supports database compatibility. The Portal hosts information about the whole MEDICOM system (Common Database) and summarized descriptions of medical devices (Short Description Database); the manufacturers servers present extended descriptions. The Portal provides end-user profiling and registration, an efficient product searching mechanism, bulletin boards, links to on-line libraries and standards, on-line information for the MEDICOM system, and special messages or advertisements from manufacturers. Platform independence and interoperability characterize the system design. Relational Database Management Systems are used for the system s databases. The end-user interface is implemented using HTML, Javascript, Java applets, and XML documents. Communication between the Portal and the manufacturers servers is implemented using a CORBA interface. Remote administration of the Portal is enabled by dynamically-generated HTML interfaces based on XML documents. A representative group of users evaluated the system. The aim of the evaluation was validation of the usability of all of MEDICOM s functionality. The evaluation procedure was based on ISO/IEC 9126 Information technology - Software product evaluation - Quality characteristics and guidelines for their use. RESULTS: The overall user evaluation of the MEDICOM system was very positive. The MEDICOM system was characterized as an innovative concept that brings significant added value to medical-equipment commerce. CONCLUSIONS: The eventual benefits of the MEDICOM system are (a) establishment of a worldwide accessible marketplace between manufacturers and health care professionals that provides up-to-date and high-quality product information in an easy and friendly way and (b) enhancement of the efficiency of marketing procedures and after-sales support. PMID- 11772548 TI - A Java-based electronic healthcare record software for beta-thalassaemia. AB - BACKGROUND: Beta-thalassaemia is a hereditary disease, the prevalence of which is high in persons of Mediterranean, African, and Southeast Asian ancestry. In Greece it constitutes an important public health problem. Beta-thalassaemia necessitates continuous and complicated health care procedures such as daily chelation; biweekly transfusions; and periodic cardiology, endocrinology, and hepatology evaluations. Typically, different care items are offered in different, often-distant, health care units, which leads to increased patient mobility. This is especially true in rural areas. Medical records of patients suffering from beta-thalassaemia are inevitably complex and grow in size very fast. They are currently paper-based, scattered over all units involved in the care process. This hinders communication of information between health care professionals and makes processing of the medical records difficult, thus impeding medical research. OBJECTIVES: Our objective is to provide an electronic means for recording, communicating, and processing all data produced in the context of the care process of patients suffering from beta-thalassaemia. METHODS: We have developed - and we present in this paper - Java-based Electronic Healthcare Record (EHCR) software, called JAnaemia. JAnaemia is a general-purpose EHCR application, which can be customized for use in all medical specialties. Customization for beta-thalassaemia has been performed in collaboration with 4 Greek hospitals. To be capable of coping with patient record diversity, JAnaemia has been based on the EHCR architecture proposed in the ENV 13606:1999 standard, published by the CEN/TC251 committee. Compliance with the CEN architecture also ensures that several additional requirements are fulfilled in relation to clinical comprehensiveness; to record sharing and communication; and to ethical, medico-legal, and computational issues. Special care has been taken to provide a user-friendly, form-based interface for data entry and processing. RESULTS: The experience gained through the use of JAnaemia in 4 Greek hospitals reveals a significant contribution towards (1) improvement of the quality of the data being recorded, since data entry is guided by appropriate forms, (2) easier cooperation between physicians, who share a common information repository, and (3) increased processing capabilities, which facilitate medical research. CONCLUSIONS: JAnaemia appears to be a useful tool, which can improve the quality of care offered to beta-thalassaemic patients in Greece. PMID- 11772549 TI - An ontology of quality initiatives and a model for decentralized, collaborative quality management on the (semantic) World-Wide-Web. AB - This editorial provides a model of how quality initiatives concerned with health information on the World Wide Web may in the future interact with each other. This vision fits into the evolving "Semantic Web" architecture - ie, the prospective that the World Wide Web may evolve from a mess of unstructured, human readable information sources into a global knowledge base with an additional layer providing richer and more meaningful relationships between resources. One first prerequisite for forming such a "Semantic Web" or "web of trust" among the players active in quality management of health information is that these initiatives make statements about themselves and about each other in a machine processable language. I present a concrete model on how this collaboration could look, and provide some recommendations on what the role of the World Health Organization (WHO) and other policy makers in this framework could be. PMID- 11772551 TI - Phosphorus affects growth and partitioning of nitrogen to Rubisco in Pinus pinaster. AB - We tested the hypothesis that photosynthetic and growth responses to phosphorus (P) are functions of differences in the partitioning of nitrogen (N) among different compounds, particularly ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). We tested this hypothesis in: (a) a greenhouse experiment with mycorrhizal seedlings of Pinus pinaster Ait. grown in sand culture for 4 months with six factorial combinations of N (0.125 and 2.0 mM) and P (0.02, 0.08 and 0.34 mM); and (b) a field study in which P was applied at five rates (up to 175 kg ha-1) to 2-year-old P. pinaster growing on P-deficient siliceous sand. After 4 months of nutrient addition or 2 years after fertilizer application, we measured light-saturated rates of photosynthesis, growth, and N and P allocation in needles. Growth of P. pinaster increased significantly with increasing concentrations of P, as did the concentration of P in needles. Concentrations of P and Rubisco were positively related, whereas those of N and Rubisco were unrelated. At low-P supply, the Rubisco/Chl ratio varied between 8.5 and 12 mmol mol-1. With P supply in excess of requirement (needle N:P ratio = 2-12) the Rubisco/Chl ratio increased to between 24 and 26 mmol mol-1. Rates of light saturated photosynthesis were unaffected by P supply because adequate concentrations of P were maintained in plants in all treatments. Orthophosphate accumulated in needles of plants receiving a high P supply, which may allow growth to continue for periods under P deficiency, provided that other nutrients also accumulate. In the case of N, Rubisco may fill this role. PMID- 11772552 TI - Response of a mature Pinus laricio plantation to a three-year restriction of water supply: structural and functional acclimation to drought. AB - The response of mature forest stands to a reduction in water availability has received little attention. In particular, the extent to which a short-term reduction in gas exchange can be alleviated in the long-term by acclimation processes is not well understood. We studied the impact of a severe reduction in water availability on the water relations and growth of 35-year-old Pinus laricio Poiret. trees in a replicated experiment. Sapwood and needle increments, soil and tree water status, stand transpiration, xylem embolism and plant hydraulic architecture were monitored over a 3-year period in control and drought-treated plots. Needle length was reduced in drought-treated trees by 30, 19 and 29%, and sapwood increments by 50, 27 and 24% over the 3 years. Drought did not result in tree mortality or in extensive xylem embolism or foliage dieback. On the contrary, a conservative water-use strategy was observed, because minimum leaf water potentials did not differ between treatments or over the season. Plant hydraulic resistance was also unaffected by restricted water availability. Stand transpiration was strongly reduced by drought treatment over the summer, but not during the winter, despite significant differences in leaf area between control and drought-treated trees, implying higher transpiration rates per unit leaf area in the droughted plants. This suggests that water transport capacity, rather than the amount of leaf area, controlled stand transpiration, which is at variance with expectations based on experiments with seedlings and short-term experiments with mature trees. PMID- 11772550 TI - Seasonal variation in nitrogen net uptake and root plasma membrane H+-ATPase activity of Scots pine seedlings as affected by nutrient availability. AB - We examined changes in nitrogen (N) net uptake and activity and amount of plasma membrane H+-ATPase (PM-ATPase) in roots of hydroponically cultured Scots pine (Pinus sylvestris L.) seedlings throughout a simulated second growing season. Seedlings were grown with low (0.25 mM N) or high (2.5 mM N) nutrient availability to determine whether root PM-ATPase is dependent on an external nutrient supply. Climatic conditions in the growth chamber simulated the mean growing season from May to mid-October in southern Finland. Root PM-ATPase activity varied considerably during the growing season and was higher in current year roots than in previous-year roots. Total PM-ATPase activity of current-year roots was highest at the end of the growing season, whereas PM-ATPase activity per unit fresh mass of current-year roots and specific absorption rate of N were highest in mid-July and decreased at the end of the growing season. This indicates that the decrease in PM-ATPase activity per unit fresh mass of the roots at the end of the growing season was compensated by the increased size of the root system. Seasonal variation in PM-ATPase activity had no clear dependence on root zone temperature. The response of PM-ATPase to root zone temperature was dependent on the developmental stage of the seedling. High nutrient availability resulted in increased root PM-ATPase activity and an extended period of root growth in autumn. PMID- 11772553 TI - Variation in specific needle area of old-growth Douglas-fir in relation to needle age, within-crown position and epicormic shoot production. AB - Variation in specific needle area (SNA; cm2 projected fresh needle area g-1 oven dried needle weight) was investigated in relation to needle age, within-crown position and epicormic shoot production in 450-year-old Douglas-fir (Pseudotsuga menziesii Mirb. (Franco) var. menziesii) trees. Specific needle area decreased with increasing needle age. The magnitude and rate of change in SNA with needle age were greatest for lower-crown branches, and decreased toward the middle- and upper-crown branches. For all branches, there was no difference between regular and epicormic shoots in the relationship between SNA and needle age. Specific needle area decreased with increasing distance from branch base, and this relationship was significant for the majority of needle age classes of the upper- and middle-crown branches. In the lowercrown branches, SNA did not vary with distance from branch base for the majority of needle age classes. For all branches, there was no difference between regular and epicormic shoots in the relationship between SNA and distance from branch base for the majority of needle age classes. These results indicate that renewal of foliage by epicormic shoot production maintains needle quality. Branch SNA increased linearly with decreasing height in the crown at a mean rate of 0.951 +/- 0.110 cm2 g-1 per vertical meter. Total needle area of branches was estimated from total needle dry weight taking into account within-branch variation in SNA. Analyses of allometric relationships between branch size and foliage amount (needle area and needle dry weight) showed that branch length was a better predictor of foliage amount than branch diameter for old Douglas-fir trees. Total needle dry weight and needle area of the sample trees, estimated from branch length and branch height and taking into account vertical within-crown variation in branch SNA, ranged from 42.4 to 154.2 kg and from 246.2 to 816.0 m2 per tree, respectively. PMID- 11772554 TI - Influence of tree internal nitrogen reserves on the response of beech (Fagus sylvatica) trees to elevated atmospheric carbon dioxide concentration. AB - We examined the influence of plant internal nitrogen (N) reserves on the response of 3-year-old beech (Fagus sylvatica L.) trees to elevated atmospheric CO2 concentration ([CO2]) in a dual 15N and 13C long-term labeling experiment. Trees were grown on sand and received either no N nutrition (-N treatment) or 4 mM N (+N treatment) for 1 year. The -N and +N pretreated trees were then placed in growth chambers and grown in 350 (ambient) or 700 ppm (elevated) of a 13CO2 atmosphere for 24 weeks. In all treatments, trees were supplied with 4 mM 15N during the experiment. Irrespective of tree N reserves, elevated [CO2] increased cumulative carbon (C) uptake by about 30% at Week 24 compared with that for trees in the ambient treatment. Elevated [CO2] also caused a shift in C allocation to belowground compartments, which was more pronounced in -N trees than in +N trees. In +N trees, belowground allocation of new C at Week 24 was 67% in ambient [CO2] compared with 70% in elevated [CO2]. The corresponding values for -N trees were 70 and 79%. The increase in C allocation in response to elevated [CO2] was most evident as an increase in belowground respiration; however, specific root respiration was unaffected by the CO2 or N treatments. Although elevated [CO2] increased root growth and belowground respiration, it had no effect on N uptake at Week 24. As a result of increased C uptake, N concentrations were decreased in trees in the elevated [CO2] treatment compared with trees in the ambient treatment in both N treatments. Partitioning of new N uptake was unaffected by elevated [CO2] in +N trees. In -N trees, however, N allocation to the stem decreased in response to elevated [CO2] and N allocation to fine roots increased, suggesting a reduction in the formation of N reserves in response to elevated [CO2]. We conclude that the response of beech trees to elevated [CO2] is affected by internal N status and that elevated [CO2] may influence the ability of the trees to form N reserves. PMID- 11772555 TI - Annual shoot growth components related to growth of Pinus brutia. AB - Shoot elongation patterns of Pinus brutia Ten. were studied in six natural populations and 10 open-pollinated families within each population. The data were collected from a provenance-progeny trial that was thinned at Ages 13 and 17 years. Annual height increment was partitioned into first flush (spring shoot) and subsequent flushes (summer shoots) and the contribution of each to annual height increment was measured from Ages 7 to 17. Spring shoot elongation patterns were similar in all populations and families for 9 out of 10 years. In contrast, at all ages, populations differed significantly in total summer shoot growth and number of summer flushes. Families within populations differed in number of summer flushes in 7 out of 10 years. Summer shoot growth was the major cause of the differences in annual height growth among the six populations. Significant and high correlations were observed between summer shoot growth at Ages 7 to 12 and height at Age 13. A population from near the middle of the species' altitudinal range had more summer flushes than populations from higher or lower elevations, indicating an opportunistic growth pattern. Compared with mid elevation populations, low- and high-elevation populations had more conservative growth patterns that depended mainly on growth of spring shoots. We conclude that summer shoot growth can serve as an explanatory variable to predict height growth of populations. Differences in shoot elongation patterns among Pinus brutia populations may be useful for selecting seed sources and for gene conservation programs. PMID- 11772556 TI - Ethylene metabolism in Scots pine (Pinus sylvestris) shoots during the year. AB - Ethylene evolution, concentrations of 1-aminocyclopropane-1-carboxylic acid (ACC) and ACC conjugates, activities of ACC synthase and ACC oxidase, and cambial growth as measured by tracheid production were monitored from November to July in 1-year-old shoots, and between July and September in current-year shoots, of Scots pine (Pinus sylvestris L.). Needles, buds and four stem parts (cortex, phloem, cambial region and mature xylem) were surveyed. Ethylene evolution was quantified by gas chromatography. Free ACC and bound ACC (after acidic hydrolysis of ACC conjugates) were quantified by combined gas chromatography-mass spectrometry, with [2H]ACC as an internal standard. Activities of ACC synthase and ACC oxidase were measured in crude protein extracts. We detected high activities of ACC synthase in needles and buds, but not in stem fractions except the phloem. In July, during the period of intensive shoot growth, we found ACC only in buds and needles. In contrast, ACC oxidase activity was high in stem tissues, particularly in the cambial region during the period of rapid tracheid production, but no ACC oxidase activity was detected in needles and buds. Nevertheless, needles evolved large amounts of ethylene. Ethylene was produced by all stem fractions, and the peak rate of ethylene evolution in the cambial region coincided with the period of maximal tracheid production. Conjugated ACC was present in every fraction except mature xylem. The concentration of conjugated ACC decreased when rates of tracheid production and ethylene evolution were high, suggesting that conjugated ACC may serve as a source for ACC in the cambial region. The regulation of ethylene biosynthesis in Scots pine shoots is discussed. PMID- 11772557 TI - Measurement carbon dioxide concentration does not affect root respiration of nine tree species in the field. AB - Inhibition of respiration has been reported as a short-term response of tree roots to elevated measurement CO2 concentration ([CO2]), calling into question the validity of root respiration rates determined at CO2 concentrations that differ from the soil [CO2] in the rooting zone. Our objectives were to validate previous observations of a direct CO2 effect on root respiration in sugar maple (Acer saccharum Marsh.) and to determine if high [CO2] also inhibited root respiration in other tree species. Root respiration rates for nine common North American tree species were measured in the field at ambient soil temperature at both 350 and 1000 microl CO2 l-1. No evidence of direct inhibition of root respiration by elevated measurement [CO2] was found for any of the species tested. The ratio of respiration rates at 1000 and 350 microl CO2 l-1 ranged from 0.97 to 1.07, and the 95% confidence intervals for this ratio included unity for all species tested. Tests of a respiration cuvette used in earlier experiments suggested that gas leakage from the cuvette/IRGA system created an apparent direct CO2 effect on respiration of sugar maple roots when none actually existed. Small sample masses used in those experiments exacerbated the error. Careful attention to the possibility of gas leaks and the avoidance of small sample masses should produce data that will allow researchers to accurately assess whether direct effects of measurement [CO2] exist. Our findings of no direct CO2 effect on respiration of roots of a wide variety of species suggest that such effects may be less common than previously thought for tree roots. PMID- 11772559 TI - Angle-closure glaucoma. PMID- 11772560 TI - Normal-tension glaucoma history. PMID- 11772562 TI - Normal-tension glaucoma. PMID- 11772564 TI - Monofixation syndrome and anisometropia. PMID- 11772566 TI - Retrobulbar anesthesia. PMID- 11772567 TI - Retrobulbar anesthesia. PMID- 11772568 TI - Peribulbar anesthesia. PMID- 11772571 TI - Point: to peel or not to peel, that is the question. PMID- 11772572 TI - Counterpoint: to peel or not to peel: is that the question? PMID- 11772573 TI - Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. AB - PURPOSE: To assess commonly used cataract surgery bacterial endophthalmitis prophylaxis techniques based on a systematic literature review and evidence rating. CLINICAL RELEVANCE: Prophylactic techniques to decrease the risk of bacterial endophthalmitis related to cataract surgery are commonly used, but the evidence justifying their use is unclear. LITERATURE REVIEWED: A MEDLINE search of the literature published in English or with English abstracts from 1966 to 2000 was performed using various combinations of relevant key words. Eighty-eight peer-reviewed papers were identified and judged worthy of review on the basis of predefined criteria. RESULTS: No prophylactic technique received the highest of three possible clinical recommendations (A, crucial to clinical outcome). Preoperative povidone-iodine preparation received the intermediate clinical recommendation (B, moderately important to clinical outcome). All other reported prophylactic interventions, including postoperative subconjunctival antibiotic injection, preoperative lash trimming, preoperative saline irrigation, preoperative topical antibiotics, antibiotic-containing irrigating solutions, and the use of intraoperative heparin, received the lowest clinical recommendation (C, possibly relevant but not definitely related to clinical outcome) based on weak and often conflicting evidence justifying their use. CONCLUSIONS: With regard to bacterial endophthalmitis prophylaxis in cataract surgery, current literature most strongly supports the use of preoperative povidone-iodine antisepsis. PMID- 11772575 TI - Adaptive effects of 30-night wear of hyper-O(2) transmissible contact lenses on bacterial binding and corneal epithelium: a 1-year clinical trial. AB - OBJECTIVE: To determine effects of lens type and oxygen transmissibility on human corneal epithelium during extended wear (EW). DESIGN: Prospective, randomized, double-masked, single-center, parallel treatment groups, 1-year clinical trial. PARTICIPANTS: One hundred seventy-eight patients completed the study: (1) high O(2) soft lens (6-night [N] EW) (n = 27); (2) hyper-O(2) soft lens (6N-EW, n = 33) or (30N-EW, n = 66); and (3) hyper-O(2) rigid gas-permeable lens (RGP) (30N EW, n = 52). INTERVENTION: Irrigation chamber to collect exfoliated corneal surface cells, confocal microscopy, and tear collection at baseline, 1, 3, 6, 9, 12 months of EW. MAIN OUTCOME MEASURES: (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal surface cells; (2) central epithelial thickness; (3) superficial epithelial cell area; (4) epithelial surface cell exfoliation; and (5) tear lactate dehydrogenase. RESULTS: Quantitative evidence demonstrated increased binding of PA to human exfoliated corneal epithelial cells during the first 3 months of soft lens EW; the control high-O(2) test lens showed significantly higher bacterial binding (P < 0.05). Binding activity gradually decreased thereafter and returned to baseline after 9 and 12 months. The corneal epithelium demonstrated enlargement of surface cell size, thinning of central epithelium, and a significant decrease in surface cell shedding (P < 0.05). Remarkably, there was subsequent partial adaptive recovery in cell shedding and epithelial thickness but not surface cell size. There was no significant difference between 6N and 30N continuous wear of the hyper-O(2) soft lens for all outcome measures. Importantly, hyper-O(2) RGP lens wear did not show significantly increased PA binding during 1 year. CONCLUSIONS: This study establishes three important new findings: (1) hyper-O(2) soft lens EW produces significantly less PA binding than the lower O(2) soft lens with no significant difference in PA binding with 6N versus 30N EW of the hyper-O(2) soft lens; (2) there is a remarkable adaptive recovery after 6 months with all soft lens wear with gradual return to prelens PA binding levels and partial recovery of other outcome measures for all test lenses EW except surface cell size; (3) 30N EW of the hyper-O(2) RGP lens produced no significant increases in PA binding over 1 year. Taken together, these results suggest that introduction of new hyper-O(2) transmissible lens materials into clinical use may offer safer EW, and future epidemiologic studies of ulcerative infectious keratitis should consider both lens type and time in lens EW in any incidence/risk analysis. PMID- 11772577 TI - Reactivations of ocular toxoplasmosis after cataract extraction. AB - PURPOSE: To determine the risk of reactivation of ocular toxoplasmosis following cataract extraction. DESIGN: Retrospective case-control study. PARTICIPANTS: Out of 154 patients with ocular toxoplasmosis, 14 patients (15 eyes) who had undergone a cataract extraction and 45 age- and sex- matched controls without cataract were selected. INTERVENTION: A review of the medical records of 14 patients with ocular toxoplasmosis and cataract and 45 control patients with ocular toxoplasmosis but without cataract. The clinical records of the controls and patients were assessed for an identical 4-month period following the date of the cataract extraction in the index patients. MAIN OUTCOME MEASURES: Development of a new active retinal lesion within 4 months after cataract surgery in patients and age -and sex matched-controls. The presence of risk factors such as sex, congenital or postnatal acquisition of ocular toxoplasmosis, age at first clinical manifestation of ocular toxoplasmosis, total number of attacks per affected eye, type of cataract, age at the time of cataract surgery and the intervals between surgery and first clinical manifestation of ocular toxoplasmosis and between surgery and the last recurrence of ocular toxoplasmosis, as well as the use of antiparasitic medication during surgery, type and complications of surgery and optimal visual acuity before and after cataract surgery. RESULTS: Reactivations of ocular toxoplasmosis following cataract extraction occurred in 5/14 patients (5/15 eyes), which was higher than the incidence of recurrences in age -and sex-matched controls (p < 0.001). No additional risk factors for the development of recurrences of ocular toxoplasmosis after cataract surgery were found. Incidence of recurrences preceding surgery did not differ between patients and controls. CONCLUSION: We identified an increased risk of reactivation of ocular toxoplasmosis following cataract extraction which implies that prophylactic treatment with antiparasitic drugs during and after the cataract surgery might be worthwhile for patients at risk of visual loss. PMID- 11772579 TI - Risk factors for self-reported visual symptoms with Intacs inserts for myopia. AB - OBJECTIVE: Potential risk factors and visual performance measures were evaluated for relationship to self-report of clinical visual symptoms after the refractive procedure for placement of Intacs microthin prescription inserts for myopia. DESIGN: Retrospective nonrandomized comparative study. PARTICIPANTS/INTERVENTION: Patients were participants in the U.S. Food and Drug Administration phase III KeraVision prospective clinical trials. MAIN OUTCOME MEASURES: Study participants (n = 263) were retrospectively classified into one of three outcome groups on the basis of postoperative self-reported visual symptoms and/or request for Intacs inserts removal through month 24. Differences between outcome groups in visual acuity, refractive error, corneal geometry, corneal topography, type of preoperative corrective lens wear, and demographic variables were evaluated with multivariate logistic regression. RESULTS: Clinical trial participants who had preoperative mean keratometry >45 diopters (D) (adjusted odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21, 0.85, P = 0.02), manifest refractive astigmatism of 0.75 D or 1.00 D (adjusted OR, 0.52; 95% CI, 0.25, 1.08, P = 0.08), measured uncorrected visual acuity > or =2 lines better than that predicted by their respective cycloplegic refractive error (adjusted OR, 0.39; 95% CI, 0.14, 1.12, P = 0.08) and/or had worn soft contact lenses (adjusted OR, 0.58; 95% CI, 0.32, 1.04, P = 0.07) tended to be less likely to report postoperative clinical visual symptoms with Intacs inserts. Risk of clinical visual symptoms and request for Intacs inserts removal approximately doubled for each 0.50 D of additional postoperative defocus equivalent (crude OR, 1.86; 95% CI, 1.39, 2.48, P = 0.00). Controlling for postoperative defocus and important preoperative risk factors, subjects who reported significant clinical visual symptoms were more likely to have had preoperative uncorrected visual acuity that was worse than that predicted by their respective cycloplegic refractive error (adjusted OR, 1.84; 95% CI, 0.98, 3.42, P = 0.06). Risk of reporting clinical visual symptoms was increased with mesopic pupil diameter > or =6.5 mm (adjusted OR, 1.76; 95% CI, 0.96, 3.24, P = 0.07). Within the group of patients who reported postoperative clinical visual symptoms, 71 of 122 (58%) had ceased reporting them by month 24. CONCLUSIONS: Adjusting for important risk factors simultaneously, this study suggested that certain preoperative characteristics may increase or decrease the likelihood, depending on the characteristic, of refractive surgery candidates to report significant clinical visual symptoms with Intacs inserts. PMID- 11772580 TI - Laser in situ keratomileusis intraoperative complications using one type of microkeratome. AB - OBJECTIVE: To identify the incidence and refractive outcome of intraoperative laser in situ keratomileusis (LASIK) complications using one type of microkeratome. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Three hundred thirty-four consecutive myopic LASIK patients (September 1997 to November 1998) operated on by one surgeon. INTERVENTION: Myopic LASIK surgeries were performed with the Mediate Mel 60 Aesculap Meditec Laser system. MAIN OUTCOME MEASURES: Preoperative and 1-year postoperative spherical equivalent, best spectacle-corrected visual acuity (BSVA), and corneal anatomic features (as obtained from videokeratography) were recorded, as was the incidence of intraoperative complications. RESULTS: Forty-eight (14%) eyes had keratome related complications. Thirty-seven (77%) eyes were immediately treated; the remaining eyes were treated on a later date. One year after treatment, 13% of the immediately treated complicated eyes maintained the preoperative BSVA; 24% had a 1-line loss; 2.7% had a greater loss of BSVA. CONCLUSIONS: Microkeratome-related complications may result in loss of BSVA. The complication of an irregular flap had the poorest refractive outcome in this series of eyes. We did not find any statistically significant relationship between corneal anatomic factors and keratome-related complications in this series. PMID- 11772581 TI - Efficacy and safety of immediate anterior chamber paracentesis in the treatment of acute primary angle-closure glaucoma: a pilot study. AB - OBJECTIVE: To study the safety and effectiveness of immediate anterior chamber paracentesis, combined with antiglaucomatous medications, in the intraocular pressure control and relief of symptoms of acute primary angle-closure glaucoma (PACG). DESIGN: Prospective noncomparative case series. PARTICIPANTS: Eight consecutive patients with their first attack of acute PACG, with intraocular pressure > or =50 mmHg, were recruited into the study. INTERVENTION: On presentation, each patient received topical pilocarpine (4%) and timolol (0.5%), immediate anterior chamber paracentesis, and systemic acetazolamide and mannitol as primary treatment. The intraocular pressures at 15 and 30 minutes, and then at 1, 2, 3, 12, and 24 hours, were documented by applanation tonometry. MAIN OUTCOME MEASURES: Symptoms, visual acuity, intraocular pressure, corneal edema, angle status on gonioscopy, pupillary size, and reaction. RESULTS: Ten eyes of eight patients seen with acute PACG were recruited. The mean intraocular pressure was reduced from 66.6 +/- 9.1 mmHg to 15.1 +/- 3.5 mmHg immediately after paracentesis, and then to 17.1 +/- 7.0 mmHg at 15 minutes, 21.7 +/- 10.2 mmHg at 30 minutes, 22.7 +/- 11.0 mmHg at 1 hour, and 20.1 +/- 14.6 mmHg at 2 hours after paracentesis. The mean intraocular pressure was less than 21 mmHg at 2 hours and beyond. There was instant symptomatic relief for all patients. No complications from the paracentesis were encountered. CONCLUSIONS: From this preliminary study, immediate paracentesis seems to be safe and effective in controlling the intraocular pressure and eliminating symptoms in acute PACG. PMID- 11772582 TI - Conjunctival advancement versus nonincisional treatment for late-onset glaucoma filtering bleb leaks. AB - OBJECTIVE: To compare the outcomes of conjunctival advancement and nonincisional management of late-onset glaucoma filtering bleb leak. DESIGN: Retrospective, nonrandomized, comparative interventional trial. PARTICIPANTS: Fifty-one eyes of 48 persons who underwent management of late-onset glaucoma filtering bleb leak from December 1986 through December 1999 were included. Thirty-seven eyes were included in the nonincisional treatment group (aqueous suppression with lubrication or patching, bandage contact lenses, cyanoacrylate glue, autologous blood injection, or a combination thereof) and 34 eyes were included in the surgical revision group (conjunctival advancement with preservation of the preexisting bleb). Twenty eyes underwent nonincisional treatment before surgical revision and were included in each treatment group. METHODS: Retrospective chart review of bleb leaks occurring at least 2 months after trabeculectomy. Successful treatment was defined as the resolution of the bleb leak, a final intraocular pressure (IOP) of 21 mmHg or less, and no significant complications such as blebitis, endophthalmitis, or bleb dysesthesia requiring a bleb revision. MAIN OUTCOME MEASURES: Cumulative success of closure of the filtering bleb leak, complications resulting from the intervention, IOP before and after treatment, and number of glaucoma medications before and after treatment. RESULTS: The Kaplan-Meier cumulative probability of success at 12 and 24 months were 0.45 and 0.42, respectively, for the nonincisional treatment group and 0.80 and 0.80, respectively, for the surgical revision group. The overall difference between the cumulative success of surgical and nonincisional treatment was statistically significant (P = 0.0001, log-rank test). In the nonincisional treatment group, only 20 of 37 eyes (54%) achieved initial sealing of the bleb leak after the treatment, and of those, almost half (8/20) eventually failed. Reasons for failure included persistent or recurrent leak (n = 21), blebitis or endophthalmitis (n = 6, including 4 with persistent leak), and bleb dysesthesia (n = 2). All eyes in the surgical group achieved closure of the leak, however 7 eventually failed because of leak recurrence (n = 2), elevated IOP (n = 3), or bleb dysesthesia (n = 2), and 11 required additional glaucoma medications. CONCLUSIONS: Patients with late bleb leaks managed with conjunctival advancement were more likely to have successful outcomes and less likely to have serious intraocular infections than those managed more conservatively. PMID- 11772583 TI - Lens fluorophotometry after trabeculectomy in primary open-angle glaucoma. AB - OBJECTIVE: To evaluate the loss of lens transparency incurred by patients undergoing trabeculectomy. DESIGN: A prospective cohort study. PARTICIPANTS AND CONTROLS: Data corresponding to 33 eyes of 33 consecutive patients with primary open-angle glaucoma (POAG) subjected to trabeculectomy (group 1) were compared with those corresponding to 12 eyes of 12 patients with POAG receiving topical antiglaucomatous treatment (group 2). INTERVENTION: Lens fluorophotometry was performed on the group 1 patients before and 12 months after surgery. In group 2, fluorophotometry was conducted at the onset of the study and at 12 months of follow-up. MAIN OUTCOME MEASURES: Starting and final lens autofluorescence and transmittance values corresponding to each subject group were compared. RESULTS: In group 1, starting and final autofluorescence was 556.3 +/- 184.3 and 691.1 +/- 179.3 Eq ng/ml, and starting and final transmittance was 0.78 +/- 0.11 and 0.67 +/- 0.14, respectively. Respective values for group 2 were 574.3 +/- 94.8 and 595.2 +/- 107.0 Eq ng/ml and 0.72 +/- 0.17 and 0.71 +/- 0.16. The mean change between final and initial autofluorescence was statistically different between groups (134.7 +/- 123.7, group 1, 20.9 +/- 25.1 Eq ng/ml, group 2; P < 0.001). Similarly, a significant difference (P < 0.001) in transmittance change was observed between the surgery and control groups (-0.11 +/- 0.072, group 1; 0.02 +/- 0.008, group 2) CONCLUSIONS: It was demonstrated by lens fluorophotometry that trabeculectomy in POAG leads to a loss in lens transparency. PMID- 11772584 TI - Association of candidemia and retinopathy of prematurity in very low birthweight infants. AB - OBJECTIVE: To determine if the presence of candidemia in infants is associated with an increased incidence of threshold retinopathy of prematurity (ROP). DESIGN: Retrospective, case-controlled study. PARTICIPANTS AND CONTROLS: Forty six infants admitted to the Texas Children's Hospital Neonatal Intensive Care Unit between 1989 and 1999 with a birth weight 1500 g or less, estimated gestational age (EGA) 28 weeks or less, and in whom candidemia developed were matched to a control group of 46 infants based on corresponding birth weight, EGA, and year of birth. METHODS: Records of each infant were reviewed to determine the presence and severity of ROP. MAIN OUTCOME MEASURES: Development of threshold ROP, including retinal detachment. RESULTS: Forty-three infants (93.5%) with candidemia and 39 (84.8%) without candidemia had ROP. Twenty-four infants (52.2%) with candidemia reached threshold and required surgical intervention, compared with 11 infants (23.9%) without candidemia (adjusted odds ratio [OR], 7.4; 95% confidence interval [CI], 1.7-32.1; P = 0.008). Retinal detachment developed in 10 of 24 candidemic infants (41.7%) who reached threshold ROP, compared with 2 of 11 infants (18.2%) without candidemia (OR, 4.4; 95% CI, 0.73 26.9; P = 0.1). CONCLUSIONS: Candidemia is associated with increased risk of threshold ROP. Infants with Candida sepsis should be monitored closely for the development of ROP and progression after treatment. PMID- 11772585 TI - Perinatal cortical and subcortical visual loss: mechanisms of injury and associated ophthalmologic signs. AB - PURPOSE: To determine whether term and preterm injuries to the retrogeniculate visual system are associated with recognizable patterns of ophthalmologic abnormalities and whether these patterns can be attributed to cortical (gray matter) or subcortical (white matter) injury. DESIGN: A retrospective case series. PARTICIPANTS: One hundred children with clinical and neuroimaging signs of perinatal posterior visual pathway injury who were examined at Arkansas Children's Hospital Eye Clinic between 1989 and 1999. METHODS: We reviewed magnetic resonance images or computed tomographic scans from 50 children with cortical (predominantly or exclusively involving cortical gray matter) and 50 children with subcortical (predominantly or exclusively involving subcortical white matter) perinatal injury to the retrogeniculate visual system. Ophthalmologic abnormalities were analyzed retrospectively in each group. MAIN OUTCOME MEASURES: Conjugate gaze deviation, type of strabismus, abnormal eye movements, and optic disc morphology. RESULTS: Horizontal conjugate gaze deviation, exotropia, and a normal optic disc appearance were significantly more common in cortical than in subcortical visual loss. Tonic downgaze, esotropia, and optic nerve hypoplasia (with or without coexisting pallor) were significantly more common in subcortical than in cortical visual loss. CONCLUSIONS: Perinatal cortical and subcortical visual loss produce differing profiles of ophthalmologic dysfunction. A reclassification of periventricular leukomalacia and other forms of retrogeniculate white matter injury as subcortical visual loss would increase diagnostic specificity. PMID- 11772586 TI - Vitreous hemorrhage is a common complication of pediatric pars planitis. AB - OBJECTIVE: To report the prevalence of vitreous hemorrhage in pars planitis and to compare the prevalence of hemorrhage for children and adults with the disease. DESIGN: A retrospective, cross-sectional observational study. PARTICIPANTS: One hundred eighteen consecutive patients with pars planitis who were evaluated at the Oregon Health and Science University Uveitis Clinic between September 1985 and April 2000. METHOD: A review of clinical records. MAIN OUTCOME MEASURES: For all patients, we recorded presence or absence of vitreous hemorrhage, as well as laterality and cause. Children were defined as being age 16 years or younger at diagnosis, and adults were defined as being aged 17 years or older at diagnosis. RESULTS: Fourteen percent of patients with pars planitis experienced vitreous hemorrhage. Persons with hemorrhage were significantly younger at the time of disease diagnosis than persons without hemorrhage (P = 0.040). The difference in prevalence of vitreous hemorrhage between children (28%) and adults (6%) was statistically significant (P = 0.003). The difference in prevalence of hemorrhage as a presenting feature between children (20%) and adults (1%) was also statistically significant (P = 0.001). CONCLUSIONS: Children with pars planitis are more likely than adults to experience vitreous hemorrhage. Pars planitis should be considered in the differential diagnosis of pediatric vitreous hemorrhage. PMID- 11772587 TI - Optic neuritis after anthrax vaccination. AB - OBJECTIVE: To report the occurrence of optic neuritis after anthrax vaccination in two patients. DESIGN: Observational case reports, review of literature. METHODS: Description of clinical history, examination, neuroimaging, and further studies in two patients experiencing optic neuritis in temporal association with anthrax vaccination. MAIN OUTCOME MEASURES: Visual acuity, visual fields. RESULTS: Two patients, 39 and 23 years of age, were seen with acute optic neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination and successfully treated with intravenous methylprednisolone. The first patient had a typical presentation and course of unilateral retrobulbar optic neuritis with excellent visual recovery. The second patient had a bilateral anterior optic neuritis and has required chronic immunosuppression to maintain his vision. Retinal and optic nerve autoantibodies were present in the second patient. No cross-reactive epitopes between anthrax vaccine and retina/optic nerve were identified. CONCLUSION: Optic neuritis is a potential adverse reaction of anthrax vaccination. PMID- 11772588 TI - Extranodal marginal zone B-cell lymphoma of the lacrimal gland associated with crystal-storing histiocytosis. AB - OBJECTIVE: Crystal-storing histiocytosis (CSH) is a very rare immunoglobulin (Ig) deposition disorder that can be associated with B-cell neoplasms as well as some reactive Ig-secreting lymphoproliferative disorders. This article reports the clinical, histopathologic, and molecular biologic findings of CSH in association with an extranodal marginal zone lymphoma (EMZL) of the lacrimal gland. DESIGN: Interventional case report with clinicopathologic correlation. INTERVENTION: Treatment consisted of conjunctival and orbital biopsies, as well as low-dose radiation of the left orbit. METHODS: Histopathologic findings of the conjunctival and orbital biopsies were compared. Further, extensive immunohistochemistry, polymerase chain reaction (PCR) for the detection of Ig heavy chain (IgH) gene rearrangement, Gene Scan analysis, and DNA sequencing were performed on all tissues. RESULTS: The tumor manifestations in the specimens demonstrated a similar morphologic and immunophenotypic characteristics consistent with the diagnosis of EMZL. Immunoglobulin H PCR and Gene Scan analysis showed B cells derived from the same clone. In association with the orbital EMZL were large accumulations histiocytes filled with refractile crystals, consistent with the diagnosis of CSH. CONCLUSIONS: The current case describes an EMZL of the lacrimal gland appearing 5 years after excision and low dose radiation of a conjunctival lymphoma. The orbital recurrence was associated with surrounding CSH, a rare Ig storage disorder more often reported in patients with multiple myeloma or lymphoplasmacytic lymphoma or immunocytoma. Ophthalmic pathologists should be aware of the diagnosis when reviewing orbital biopsies, because difficulties may arise when the crystal-storing macrophages occupy more tissue space than the Ig-secreting cells or when they resemble cell types such as rhabdomyoblasts. PMID- 11772589 TI - The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid. AB - PURPOSE: To determine the clinical outcome of patients with ocular-cicatricial pemphigoid (OCP) and the influence of systemic treatment on clinical progression. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Sixty-one patients with biopsy-proven OCP. METHODS: Patients with documented disease progression treated with chemotherapy and/or corticosteroids were followed between 1985 and 2000. The parameters evaluated were ocular stage at presentation, visual acuity, ocular complications, disease progression, control of ocular inflammation, and presence of extraocular involvement. Systemic treatment and related side effects were analyzed. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, extraocular involvement, disease progression, clinical outcome, systemic treatment, and related side effects. RESULTS: Sixty one patients (32 female; 29 male) with a mean age of 67 years were studied. Extraocular involvement was present in 50% of patients. Sixty percent of eyes were initially seen with stage III (advanced cicatrizing) disease at first evaluation. Seven percent of involved eyes at first visit and 21% at the end of follow-up were legally blind. The most common ocular complications encountered were dry eye, corneal abnormalities, and glaucoma. Dapsone was the most commonly used drug (51 patients), followed by methotrexate (24 patients), azathioprine (23 patients), and cyclophosphamide (15 patients); prednisone, always given as adjunctive treatment, was used in 17 patients. Control of ocular inflammation (total or partial) was achieved in 90% of patients, but 46% of them needed continuation of systemic treatment to avoid disease recurrences, and 10% progressed despite different drugs used. Two agents were required in 32% of cases to control disease activity. The most common treatment-related side effects were hematologic complications (n = 34) followed by gastrointestinal (n = 17), cardiovascular (n = 15), and urinary complications (n = 11). Dapsone was responsible for the greatest number of side effects (n = 43); methotrexate caused the least trouble (n = 6). Corticosteroid-related complications (n = 34) were mostly cardiovascular and endocrinologic. CONCLUSIONS: Ocular-cicatricial pemphigoid is an autoimmune disease that, untreated, progresses to conjunctival scarring and blindness; systemic immunosuppression is required to control it. Long-term systemic treatment and more than one drug are frequently necessary to avoid recurrences, exposing elderly patients to a higher risk of drug toxicity. The most frequently encountered treatment-related side effects were anemia, leukopenia, liver toxicity, and hypertension. PMID- 11772590 TI - An analysis of lesion size and location in newly diagnosed cytomegalovirus retinitis. AB - OBJECTIVE: To investigate the size and distribution of lesions in newly diagnosed cytomegalovirus retinitis (CMVR). DESIGN: Retrospective, observational case series. PARTICIPANTS: Fundus photographs of 252 newly diagnosed CMVR lesions in 173 eyes of 130 patients (123 male, 7 female). METHODS: Thirty-five millimeter (60 degrees ) color transparencies were digitized. A montage of the retina was assembled for each involved eye and was superimposed on a specially designed map of the postequatorial retina. Cytomegalovius retinitis lesions were delineated, and the size and location of each lesion was measured. The size of newly diagnosed CMVR lesions was computed in terms of percent postequatorial retinal surface area (PERSA), and the location of lesions was plotted on a polar coordinate system. MAIN OUTCOME MEASURES: Size and location of patches of newly diagnosed CMVR. RESULTS: The median lesion size was 3% PERSA. Peripheral CMVR lesions were larger than posterior ones (P < 0.001). The mean number of lesions was 1.6 per eye. The total area of CMVR involvement ranged from 1% to 76% PERSA, with a median of 5% PERSA. There was no difference between left and right eyes in the distribution of lesion centers (P = 0.27). The concentric distribution of lesion centers appeared to be homogeneous, except for fewer centers in the most peripheral 14 degrees (P < 0.001), and a greater than expected number of lesion centers in the macula (central 11.6 degrees, P < 0.001). Eyes of patients with unilateral retinitis had 1.3 lesions per involved eye compared with eyes of patients with bilateral retinitis, which had 1.6 lesions per eye (P = 0.003). CONCLUSIONS: Most newly diagnosed CMVR lesions were small. Peripheral lesions were larger than more posterior lesions. Variations from a homogeneous distribution of lesions were noted only at the extreme peripheral and central locations and are probably explained by ascertainment bias. The macula was not spared from new CMVR lesions in this patient population. PMID- 11772591 TI - Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. AB - PURPOSE: To investigate whether hypercoagulability plays a role in thrombus formation in patients with central retinal vein occlusion (CRVO) who are less than 56 years of age. DESIGN: Prospective, observational case series with retrospective comparative controls. PARTICIPANTS AND CONTROLS: Participants included 55 consecutive patients with CRVO less than 56 years of age. The laboratory's age-matched control groups were used to compare results for the same tests. METHODS: Fifty-five patients with CRVO less than 56 years old (mean age, 44 years) underwent laboratory evaluation for homocysteine, activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies. The results were compared with previously drawn age-matched control groups obtained by the same laboratory for statistical significance. MAIN OUTCOME MEASURES: Patients were considered to have a positive test if their results were outside the laboratory's established range. RESULTS: Fifteen of 55 patients (27%) had one positive test result suggesting hypercoagulability. Compared with the control groups, these patients less than 56 years old with CRVO had a higher incidence of coagulation abnormalities by laboratory testing. Among the parameters tested, hyperhomocysteinemia and circulating antiphospholipid antibodies were significantly more common in the CRVO patients (P < 0.05) compared with age matched controls. CONCLUSIONS: Hypercoagulability may play a role in the pathogenesis of CRVO in patients less than 56 years old. The cause of CRVO remains multifactorial, and laboratory tests suggesting hypercoagulable states alone cannot account for the cause in most of these patients less than 56 years of age. The authors recommend examining blood pressure, intraocular pressure, complete blood count, glucose levels, and a lipid panel on all patients with CRVO. When tests for these common risk factors for CRVO are negative, consider ordering selected tests in young patients with CRVO to rule out thrombophilias, especially in patients with bilateral CRVO, a history of previous thrombosis, or family history of thrombosis. PMID- 11772592 TI - Fluorescein angiographic features of tubulointerstitial nephritis and uveitis syndrome. AB - OBJECTIVE: To explain fluorescein angiographic features in patients with tubulointerstitial nephritis and uveitis syndrome. DESIGN: Retrospective observational case series. PARTICIPANTS: Four consecutive patients with tubulointerstitial nephritis and uveitis syndrome seen at Uveitis Service of Okayama University Hospital from 1995 to 2000. METHODS: Patients' characteristics obtained from medical records were analyzed. In addition, characteristics of 15 patients reported previously as case reports in the Japanese literature were reviewed. MAIN OUTCOME MEASURES: Clinical and fluorescein angiographic features. RESULTS: The present four patients showed varying degrees of retinal capillary leakage on fluorescein angiography, ranging from capillary leakage limited to the peripheral fundus to cystoid macular edema. The same angiographic features were found in 15 patients reported previously in the Japanese literature. CONCLUSIONS: Retinal capillary leakage of varying degrees was a common fluorescein angiographic feature in patients with tubulointerstitial nephritis and uveitis syndrome. Fluorescein angiography is valuable in assessing the extent of retinal involvement. PMID- 11772593 TI - Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts Eye and Ear Infirmary experience. AB - PURPOSE: To report our experience with the use of chlorambucil for otherwise treatment-resistant uveitis and to assess its safety and efficacy. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Twenty-eight patients with intractable noninfectious uveitis. METHODS: We reviewed the records of 28 patients (56 eyes) with chronic noninfectious uveitis who were treated with chlorambucil from 1987 to 2000. Diagnoses included Adamantiades-Behcet's disease (ABD) (7 patients), juvenile rheumatoid arthritis (JRA)-associated uveitis (10 patients), pars planitis (2 patients), sympathetic ophthalmia (1 patient), idiopathic uveitis (6 patients), Crohn's disease (1 patient), and HLA-B27 associated uveitis (1 patient). All patients were refractory to other immunomodulatory therapy and systemic steroids. The median duration of treatment with chlorambucil was 12 months (range, 4-50 months), whereas the median daily dosage was 8 mg (range, 4-22 mg). Patients were followed for a median follow-up period of 46 months (range, 4-166 months) after chlorambucil treatment was begun and continued to be followed for relapse after cessation of therapy. MAIN OUTCOME MEASURES: Visual outcome, response to treatment, treatment-related side effects, drug dosage, previous and final treatment, discontinuation of systemic corticosteroids. RESULTS: Chlorambucil was discontinued in seven patients because of side effects: two females had temporary amenorrhea develop, two patients had unacceptable gastrointestinal intolerance, one patient had infection, and 2 patients had progressive leukopenia. Nineteen patients (68%) showed positive clinical response to the treatment, four (14%) initially responded then relapsed after discontinuation of the drug, three patients with ABD had improvement of ocular disease but worsening of systemic symptoms, and two had persistent inflammation. Visual acuity was improved in 24 eyes (43%), stable in 22 (39%), and worsened in 10 eyes (18%). Systemic prednisone was successfully discontinued in 19 of the 28 patients (68%), and 14 patients were free of inflammation at the end of follow-up without any systemic medication. CONCLUSIONS: Chlorambucil can be a safe and effective alternative for preserving vision in patients with otherwise treatment resistant uveitis. PMID- 11772594 TI - Posterior scleritis associated with Borrelia burgdorferi (Lyme disease) infection. AB - OBJECTIVE: To report on the clinical findings in a patient with posterior scleritis associated with infection with Borrelia burgdorferi. DESIGN: Interventional case report. PARTICIPANT: A 39-year-old male ranger who experienced posterior scleritis after several tick bites with erythema migrans. TESTING: Extensive ophthalmic and systemic workup, including serologic testing and imaging techniques. RESULTS: Sonography and contrast-enhanced computed tomography showed a large scleral mass (16 x 12 x 13 mm) in a patient with painful proptosis in the left eye with episcleral vascular dilation, reduction in bulbar motility, and chorioretinal folds in the upper temporal quadrant. Treatment with high-dose corticosteroids resulted in rapid regression of clinical symptoms and of the scleral mass. Intensive workup revealed immunoglobulin M antibodies (enzyme-linked immunoassay, Western immunoblot) and a positive lymphocyte transformation assay against B. burgdorferi. No other cause for posterior scleritis could be identified. CONCLUSIONS: Posterior scleritis should be added to the list of ocular manifestations associated with Lyme disease. Because corticosteroids alone resulted in rapid improvement of clinical symptoms, the scleritis might be mediated by autoimmunologic mechanisms. PMID- 11772595 TI - The effect of duration of macular detachment on results after the scleral buckle repair of primary, macula-off retinal detachments. AB - PURPOSE: To present a current series that determined the effect of duration of macular detachment (DMD) and patient age on postscleral buckle (SB) visual acuity (VA) and anatomic results. DESIGN: Retrospective, noncomparative, observational case series. PARTICIPANTS: Ninety-four consecutive patients (94 eyes) with primary, uncomplicated, macula-off retinal detachments, a preoperative VA of 20/200 or worse, and a precise history of when macular function was lost. INTERVENTION: Standard explant scleral buckle technique performed by multiple surgeons. MAIN OUTCOME MEASURES: Visual acuity, anatomic reattachment, and proliferative vitreoretinopathy. RESULTS: Visual acuity after SB of 20/40 or better was seen in 71% of eyes with a DMD of 10 days or fewer, 27% of eyes with a DMD of 11 days to 6 weeks, and 14% of eyes with a DMD of more than 6 weeks. Eyes achieved a mean VA after SB of 20/41 after a DMD of 10 days or fewer, 20/121 after a DMD of 11 days to 6 weeks, and 20/178 after a DMD of more than 6 weeks. No decrease in VA was seen within the 1- to 10-day period or the 11 days to 6 week period of DMD. Patients 60 years of age or less achieved a mean VA after SB of 20/47 compared with 20/81 for patients between 61 to 75 years of age and 20 of 96 in patients more than 76 years of age. Duration of macular detachment and patient age had no statistically significant effect on final anatomic reattachment after SB, reoperation rate, or proliferative vitreoretinopathy. CONCLUSIONS: Eyes with primary, uncomplicated, macula-off retinal detachment repaired with SB achieve excellent postoperative VA if repaired within the first 10 days of macular detachment. These results are better than the VA in eyes repaired after 11 days to 6 weeks and more than 6 weeks of macular detachment. Patients 60 years of age and younger obtained better postoperative VA than older patients. Duration of macular detachment and patient age did not significantly effect anatomic outcomes. PMID- 11772597 TI - Is prophylactic 360-degree laser retinopexy protective? Risk factors for retinal redetachment after removal of silicone oil. AB - OBJECTIVES: To identify risk factors for retinal redetachment after removal of silicone oil. To determine the effectiveness of prophylactic laser in preventing retinal redetachment after removal of silicone oil. DESIGN: A nonrandomized retrospective comparative interventional trial. PARTICIPANTS: Three hundred seventy-six patients undergoing vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment at one institution over a 4-year period. Two hundred eighty-seven patients with fully attached retinas subsequently underwent removal of silicone oil. One hundred thirty-eight cases had undergone prophylactic 360 degrees laser retinopexy before removal of silicone oil, either at the time of their final retinal reattachment procedure (n = 36) or as a separate supplementary procedure (n = 102). METHODS: A retrospective case note review was performed to identify clinical and demographic factors associated with increased or reduced odds of retinal redetachment after removal of silicone oil. Both univariate and multiple variable analysis were used to identify significant risk factors. MAIN OUTCOME MEASURES: Incidence of retinal redetachment after removal of silicone oil. RESULTS: Median follow-up after removal of silicone oil was 272 days. Three hundred sixty-degree prophylactic laser retinopexy was associated with a reduction from 26% to 14% in the incidence of redetachment after removal of silicone oil (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.78; P = 0.006). Patients requiring further retinal reattachment surgery after their first oil procedure were at twice the odds of re-detachment after oil removal (adjusted odds ratio, 2.10; 95% confidence interval, 1.03-4.26; P = 0.04). CONCLUSIONS: The need for retinal reattachment surgery subsequent to a first silicone oil procedure was associated with twice the odds of retinal redetachment after removal of silicone oil. Prophylactic laser retinopexy may halve the incidence of retinal redetachment after removal of silicone oil. PMID- 11772598 TI - Comparison of intraocular light scatter in carriers of choroideremia and X-linked retinitis pigmentosa. AB - OBJECTIVE: To compare the extent of intraocular straylight in carriers of choroideremia (CHM) and X-linked recessive retinitis pigmentosa (XLRP) to clarify further the relationship between photoreceptor cell degeneration and intraocular light scatter in retinal diseases. DESIGN: Prospective case-control study. PARTICIPANTS: Six obligate carriers of CHM, 12 obligate carriers of XLRP, and 30 age-similar control subjects with normal vision. The controls had no posterior subcapsular (PSC) lens opacities, and the carriers had minimal or no PSC lens opacities, as assessed by slit-lamp biomicroscopy. MAIN OUTCOME MEASURES: Straylight levels were measured using a van den Berg Straylightmeter. Visual acuity and Goldmann visual field area using a II/4e target were assessed for both eyes of each carrier. Electroretinogram (ERG) data were available on four of six carriers of CHM and all carriers of XLRP. The extent of retinal pigment epithelial degenerative changes was evaluated by fundus examination. RESULTS: All six carriers of CHM had typical fundus abnormalities with normal visual fields. Five of the six carriers of CHM had age-normal levels of intraocular light scatter, and one showed minimally elevated intraocular light scatter. The 12 carriers of XLRP had a spectrum of fundus abnormalities and varying severity of functional impairment as derived from visual field areas and ERG amplitudes. Seven of the 12 carriers of XLRP showed an elevated level of intraocular light scatter in at least one eye. The degree of straylight elevation above the normal mean age value was correlated significantly with both visual field area and amplitude of the maximal-intensity, dark-adapted ERG b-wave. CONCLUSIONS: The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced ERG amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels. This finding supports the hypothesis that the increased levels of intraocular light scatter observed in some patients with hereditary retinal degenerations result from subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration. PMID- 11772599 TI - The expanded clinical spectrum of deferoxamine retinopathy. AB - OBJECTIVE: To describe early and unusual features in 16 patients with deferoxamine-induced retinal toxicity and to assess the role of diagnostic tests in the diagnosis and management of patients with the disorder. DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixteen patients with deferoxamine retinopathy identified from members of the Vitreous, Retina, and Macula societies of the United States. INTERVENTION/TESTING: The patients underwent complete ophthalmologic examination. Most patients were also evaluated by fluorescein angiography and electrophysiologic testing. The diagnosis was based on the medical history, systemic and ocular findings, and the results of electrophysiologic tests. MAIN OUTCOME MEASURES: Ocular symptoms, ophthalmoscopic, fluoroangiographic, and electrophysiologic findings. RESULTS: We confirmed previously reported findings in patients with established disease, including macular and/or peripheral pigmentary changes, reduced electroretinographic (ERG) amplitudes, and reduced electrooculographic (EOG) light-peak to dark-trough ratios. Peripapillary, papillomacular, and paramacular patterns of retinal pigment epithelial (RPE) degeneration were each observed in one patient. Diffuse RPE or outer retinal fluorescence by fluorescein angiography was a marker for active retinopathy both at the onset of disease and during recurrence and preceded the development of RPE pigment mottling. CONCLUSIONS: Unusual patterns of deferoxamine retinopathy may occur in addition to the foveomacular and/or peripheral patterns previously described. Fluorescein angiography is particularly useful for determining whether there is ongoing retinal/RPE injury. ERG and EOG testing may indicate earlier or more widespread injury than is suggested by fundus examination alone. Patients who do not discontinue deferoxamine after the development of retinopathy risk further retinal/RPE injury and visual deterioration. PMID- 11772600 TI - Efficacy of probing the nasolacrimal duct with adjunctive Mitomycin-C for epiphora in adults. AB - PURPOSE: To investigate the efficacy and safety of adjunctive low-dose mitomycin C during lacrimal probing for adults with blocked nasolacrimal ducts. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: From January 1998 to December 2000, a total of 32 adult patients (36 eyes) seen with epiphora caused by primary nasolacrimal duct obstruction was treated and evaluated. INTERVENTION: Lacrimal probing with adjunctive mitomycin-C (0.2 mg/ml). MAIN OUTCOME MEASURES: Objective evaluation of patency with irrigation, as well as patients' subjective assessment of improvement. RESULTS: For 32 of the treated eyes (89%), the nasolacrimal duct remained open 9 months after treatment. Repeat procedure was successful for two of the remaining four eyes with recurrent obstruction during follow-up, yielding an overall patency rate of 94%. Patient satisfaction was assessed after 9 months and indicated that the epiphora was at least mildly improved for 30 (83%) of the treated eyes. Watering was completely absent for nine eyes (25%), rated as moderately improved for 17 (47%), and mildly improved for 4 (11%). No complications were encountered over the 9-month follow up period. CONCLUSIONS: Our experience suggests good long-term results for probing with adjunctive, topical Mitomycin-C for cases of adult epiphora caused by obstruction of the nasolacrimal duct followed by repeat procedure if necessary. It can be recommended as a simple, effective, and minimally invasive technique, with no significant complications resulting from low-dose use in our study. PMID- 11772601 TI - Laser in situ keratomileusis for myopia and astigmatism: safety and efficacy: a report by the American Academy of Ophthalmology. AB - OBJECTIVE: This document describes laser in situ keratomileusis (LASIK) for myopia and astigmatism and examines the evidence to answer key questions about the efficacy and safety of the procedure. METHODS: A literature search conducted for the years 1968 to 2000 retrieved 486 citations and an update search conducted in June 2001 yielded an additional 243 articles. The panel members reviewed 160 of these articles and selected 47 for the panel methodologist to review and rate according to the strength of evidence. A Level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a Level II rating is assigned to well-designed cohort and case-control studies; and a Level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS: The assessment describes randomized controlled trials published in 1997 or later (Level I evidence) and more recent comparative and noncomparative case series (Level II and Level III evidence), focusing on results for safety and effectiveness. It is difficult to extrapolate results from these studies that are comparable to current practices with the most recent generation lasers because of the rapid evolution of LASIK technology and techniques. It is also difficult to compare studies because of variations in the range of preoperative myopia, follow-up periods, lasers, nomograms, microkeratomes and techniques, the time frame of the study, and the investigators' experience. CONCLUSIONS: For low to moderate myopia, results from studies in the literature have shown that LASIK is effective and predictable in terms of obtaining very good to excellent uncorrected visual acuity and that it is safe in terms of minimal loss of visual acuity. For moderate to high myopia (>6.0 D), the results are more variable, given the wide range of preoperative myopia. The results are similar for treated eyes with mild to moderate degrees of astigmatism (<2.0 D). Serious adverse complications leading to significant permanent visual loss such as infections and corneal ectasia probably occur rarely in LASIK procedures; however, side effects such as dry eyes, night time starbursts, and reduced contrast sensitivity occur relatively frequently. There were insufficient data in prospective, comparative trials to describe the relative advantages and disadvantages of different lasers or nomograms. PMID- 11772602 TI - Cloning, sequencing, and expression of the cold-inducible hutU gene from the antarctic psychrotrophic bacterium Pseudomonas syringae. AB - A promoter-fusion study with a Tn 5-based promoter probe vector had earlier found that the hutU gene which encodes the enzyme urocanase for the histidine utilization pathway is upregulated at a lower temperature (4 degrees C) in the Antarctic psychrotrophic bacterium Pseudomonas syringae. To examine the characteristics of the urocanase gene and its promoter elements from the psychrotroph, the complete hutU and its upstream region from P. syringae were cloned, sequenced, and analyzed in the present study. Northern blot and primer extension analyses suggested that the hutU gene is inducible upon a downshift of temperature (22 to 4 degrees C) and that there is more than one transcription initiation site. One of the initiation sites was specific to the cells grown at 4 degrees C, which was different from the common initiation sites observed at both 4 and 22 degrees C. Although no typical promoter consensus sequences were observed in the flanking region of the transcription initiation sites, there was a characteristic CAAAA sequence at the -10 position of the promoters. Additionally, the location of the transcription and translation initiation sites suggested that the hutU mRNA contains a long 5'-untranslated region, a characteristic feature of many cold-inducible genes of mesophilic bacteria. A comparison of deduced amino acid sequences of urocanase from various bacteria, including the mesophilic and psychrotrophic Pseudomonas spp., suggests that there is a high degree of similarity between the enzymes. The enzyme sequence contains a signature motif (GXGX(2)GX(10)G) of the Rossmann fold for dinucleotide (NAD(+)) binding and two conserved cysteine residues in and around the active site. The psychrotrophic enzyme, however, has an extended N-terminal end. PMID- 11772603 TI - Effect of cold starvation, acid stress, and nutrients on metabolic activity of Helicobacter pylori. AB - Helicobacter pylori can transform, in vivo as well as in vitro, from dividing spiral-shaped forms into nonculturable coccoids, with intermediate forms called U forms. The importance of nonculturable coccoid forms of H. pylori in disease transmission and antibiotic treatment failures is unclear. Metabolic activities of actively growing as well as nonculturable H. pylori were investigated by comparing the concentrations of cellular ATP and total RNA, gene expression, presence of cytoplasmic polyphosphate granules and iron inclusions, and cellular morphology during extended broth culture and nutritional cold starvation. In addition, the effect of exposing broth-cultured or cold-starved cells to a nutrient-rich or acidic environment on the metabolic activities was investigated. ATP was detectable up to 14 days and for at least 25 days after transformation from the spiral form to the coccoid form or U form in broth-cultured and cold starved cells, respectively. mRNAs of VacA, a 26-kDa protein, and urease A were detected by using reverse transcription-PCR in cells cultured for 2 months in broth or cold starved for at least 28 months. The ATP concentration was not affected during exposure to fresh or acidified broth, while 4- to 12-h exposures of nonculturable cells to lysed human erythrocytes increased cellular ATP 12- to 150-fold. Incubation of nonculturable cold-starved cells with an erythrocyte lysate increased total RNA expression and ureA mRNA transcription as measured by quantitative real-time reverse transcription-PCR. Furthermore, the number of structurally intact starved coccoids containing polyphosphate granules increased almost fourfold (P = 0.0022) under the same conditions. In conclusion, a specific environmental stimulus can induce ATP, polyphosphate, and RNA metabolism in nonculturable H. pylori, indicating viability of such morphological forms. PMID- 11772604 TI - Grassland management regimens reduce small-scale heterogeneity and species diversity of beta-proteobacterial ammonia pxidizer populations. AB - The impact of soil management practices on ammonia oxidizer diversity and spatial heterogeneity was determined in improved (addition of N fertilizer), unimproved (no additions), and semi-improved (intermediate management) grassland pastures at the Sourhope Research Station in Scotland. Ammonia oxidizer diversity within each grassland soil was assessed by PCR amplification of microbial community DNA with both ammonia oxidizer-specific, 16S rRNA gene (rDNA) and functional, amoA, gene primers. PCR products were analysed by denaturing gradient gel electrophoresis, phylogenetic analysis of partial 16S rDNA and amoA sequences, and hybridization with ammonia oxidizer-specific oligonucleotide probes. Ammonia oxidizer populations in unimproved soils were more diverse than those in improved soils and were dominated by organisms representing Nitrosospira clusters 1 and 3 and Nitrosomonas cluster 7 (closely related phylogenetically to Nitrosomonas europaea). Improved soils were only dominated by Nitrosospira cluster 3 and Nitrosomonas cluster 7. These differences were also reflected in functional gene (amoA) diversity, with amoA gene sequences of both Nitrosomonas and Nitrosospira species detected. Replicate 0.5-g samples of unimproved soil demonstrated significant spatial heterogeneity in 16S rDNA-defined ammonia oxidizer clusters, which was reflected in heterogeneity in ammonium concentration and pH. Heterogeneity in soil characteristics and ammonia oxidizer diversity were lower in improved soils. The results therefore demonstrate significant effects of soil management on diversity and heterogeneity of ammonia oxidizer populations that are related to similar changes in relevant soil characteristics. PMID- 11772605 TI - Novel alkylsulfatases required for biodegradation of the branched primary alkyl sulfate surfactant 2-butyloctyl sulfate. AB - Recent reports show that contrary to common perception, branched alkyl sulfate surfactants are readily biodegradable in standard biodegradability tests. We report here the isolation of bacteria capable of biodegrading 2-butyloctyl sulfate and the identification of novel enzymes that initiate the process. Enrichment culturing from activated sewage sludge yielded several strains capable of growth on 2-butyloctyl sulfate. Of these, two were selected for further study and identified as members of the genus Pseudomonas. Strain AE-A was able to utilize either sodium dodecyl sulfate (SDS) or 2-butyloctyl sulfate as a carbon and energy source for growth, but strain AE-D utilized only the latter. Depending on growth conditions, strain AE-A produced up to three alkylsulfatases, as shown by polyacrylamide gel electrophoresis zymography. Growth on either SDS or 2 butyloctyl sulfate or in nutrient broth produced an apparently constitutive, nonspecific primary alkylsulfatase, AP1, weakly active on SDS and on 2-butyloctyl sulfate. Growth on 2-butyloctyl sulfate produced a second enzyme, AP2, active on 2-butyloctyl sulfate but not on SDS, and growth on SDS produced a third enzyme, AP3, active on SDS but not on 2-butyloctyl sulfate. In contrast, strain AE-D, when grown on 2-butyloctyl sulfate (no growth on SDS), produced a single enzyme, DP1, active on 2-butyloctyl sulfate but not on SDS. DP1 was not produced in broth cultures. DP1 was induced when residual 2-butyloctyl sulfate was present in the growth medium, but the enzyme disappeared when the substrate was exhausted. Gas chromatographic analysis of products of incubating 2-butyloctyl sulfate with DP1 in gels revealed the formation of 2-butyloctanol, showing the enzyme to be a true sulfatase. In contrast, Pseudomonas sp. strain C12B, well known for its ability to degrade linear SDS, was unable to grow on 2-butyloctyl sulfate, and its alkylsulfatases responsible for initiating the degradation of SDS by releasing the parent alcohol exhibited no hydrolytic activity on 2-butyloctyl sulfate. DP1 and the analogous AP2 are thus new alkylsulfatase enzymes with novel specificity toward 2-butyloctyl sulfate. PMID- 11772606 TI - Differentiation of Phytophthora infestans sporangia from other airborne biological particles by flow cytometry. AB - The ability of two different flow cytometers, the Microcyte (Optoflow) and the PAS-III (Partec), to differentiate sporangia of the late-blight pathogen Phytophthora infestans from other potential airborne particles was compared. With the PAS-III, light scatter and intrinsic fluorescence parameters could be used to differentiate sporangia from conidia of Alternaria or Botrytis spp., rust urediniospores, and pollen of grasses and plantain. Differentiation between P. infestans sporangia and powdery mildew conidia was not possible by these two methods but, when combined with analytical rules evolved by genetic programming methods, could be achieved after staining with the fluorescent brightener Calcofluor white M2R. The potential application of these techniques to the prediction of late-blight epiphytotics in the field is discussed. PMID- 11772607 TI - Electrotransformation of Lactobacillus delbrueckii subsp. bulgaricus and L. delbrueckii subsp. lactis with various plasmids. AB - We describe, for the first time, a detailed electroporation procedure for Lactobacillus delbrueckii. Three L. delbrueckii strains were successfully transformed. Under optimal conditions, the transformation efficiency was 10(4) transformants per microg of DNA. Using this procedure, we identified several plasmids able to replicate in L. delbrueckii and integrated an integrative vector based on phage integrative elements into the L. delbrueckii subsp. bulgaricus chromosome. These vectors provide a good basis for developing molecular tools for L. delbrueckii and open the field of genetic studies in L. delbrueckii. PMID- 11772608 TI - Improvement of cellulolytic properties of Clostridium cellulolyticum by metabolic engineering. AB - Cellulolytic clostridia have evolved to catabolize lignocellulosic materials at a seasonal biorhythm, so their biotechnological exploitation requires genetic improvements. As high carbon flux leads to pyruvate accumulation, which is responsible for the cessation of growth of Clostridium cellulolyticum, this accumulation is decreased by heterologous expression of pyruvate decarboxylase and alcohol dehydrogenase from Zymomonas mobilis. In comparison with that of the wild strain, growth of the recombinant strain at the same specific rate but for 145 h instead of 80 h led to a 150% increase in cellulose consumption and a 180% increase in cell dry weight. The fermentation pattern was shifted significantly: lactate production decreased by 48%, whereas the concentrations of acetate and ethanol increased by 93 and 53%, respectively. This study demonstrates that the fermentation of cellulose, the most abundant and renewable polymer on earth, can be greatly improved by using genetically engineered C. cellulolyticum. PMID- 11772609 TI - Restriction fragment length polymorphisms detected with novel DNA probes differentiate among diverse lineages of serogroup 4 Listeria monocytogenes and identify four distinct lineages in serotype 4b. AB - Listeria monocytogenes of serotype 4b has been implicated in numerous outbreaks of food-borne listeriosis and in ca. 40% of sporadic cases. Strains of this serotype appear to be relatively homogeneous genetically, and molecular markers specific for distinct serotype 4b lineages have not been frequently identified. Here we show that DNA fragments derived from the putative mannitol permease locus of Listeria monocytogenes had an unexpectedly high potential to differentiate among different strains of serotype 4b when used as probes in Southern blotting of EcoRI-digested genomic DNA, yielding four distinct restriction fragment length polymorphism (RFLP) patterns. Strains of two epidemic-associated lineages, including the major epidemic clone implicated in several outbreaks in Europe and North America, had distinct RFLPs which differed from those of all other serotype 4b strains that we screened but which were encountered among strains of serotypes 1/2b and 3b. In addition, three serogroup 4 lineages were found to have unique RFLPs that were not encountered among any other L. monocytogenes strains. One was an unusual lineage of serotype 4b, and the other two were members of the serotype 4a and 4c group. The observed polymorphisms may reflect evolutionary relationships among lineages of L. monocytogenes and may facilitate detection and population genetic analysis of specific lineages. PMID- 11772610 TI - Characterization of Pseudomonas spp. associated with spoilage of gilt-head sea bream stored under various conditions. AB - The population dynamics of pseudomonads in gilt-head sea bream Mediterranean fish (Sparus aurata) stored under different conditions were studied. Phenotypic analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole cell proteins were performed to identify a total of 106 Pseudomonas strains isolated from S. aurata stored under different temperatures (at 0, 10, and 20 degrees C) and packaging conditions (air and a modified atmosphere of 40% CO(2) 30% N(2)-30% O(2)). Pseudomonas lundensis was the predominant species, followed by Pseudomonas fluorescens, while Pseudomonas fragi and Pseudomonas putida were detected less frequently. Fluorescent Pseudomonas strains dominated under air conditions, while proteolytic and less lipolytic strains dominated under modified atmosphere packaging. Different storage conditions appear to govern the selection of pseudomonads in gilt-head sea bream fish. PMID- 11772611 TI - Ammonia- and nitrite-oxidizing bacterial communities in a pilot-scale chloraminated drinking water distribution system. AB - Nitrification in drinking water distribution systems is a common operational problem for many utilities that use chloramines for secondary disinfection. The diversity of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in the distribution systems of a pilot-scale chloraminated drinking water treatment system was characterized using terminal restriction fragment length polymorphism (T-RFLP) analysis and 16S rRNA gene (ribosomal DNA [rDNA]) cloning and sequencing. For ammonia oxidizers, 16S rDNA-targeted T-RFLP indicated the presence of Nitrosomonas in each of the distribution systems, with a considerably smaller peak attributable to Nitrosospira-like AOB. Sequences of AOB amplification products aligned within the Nitrosomonas oligotropha cluster and were closely related to N. oligotropha and Nitrosomonas ureae. The nitrite oxidizing communities were comprised primarily of Nitrospira, although Nitrobacter was detected in some samples. These results suggest a possible selection of AOB related to N. oligotropha and N. ureae in chloraminated systems and demonstrate the presence of NOB, indicating a biological mechanism for nitrite loss that contributes to a reduction in nitrite-associated chloramine decay. PMID- 11772612 TI - Occurrence of beauvericin and enniatins in wheat affected by Fusarium avenaceum head blight. AB - We evaluated Fusarium contamination and the levels of hexadepsipeptide mycotoxins in 13 wheat samples affected by head blight in Finland. Fusarium avenaceum was the dominant species (91%) isolated from all samples, but isolates of F. culmorum (4%), F. tricinctum (3%), and F. poae (2%) also were recovered. Beauvericin (0.64 to 3.5 microg/g) was detected in all 13 samples. Enniatin B (trace to 4.8 microg/g) was detected in 12 samples, enniatin B(1) (trace to 1.9 microg/g) was detected in 8 samples, and enniatin A(1) (trace to 6.9 microg/g) was detected in 10 samples. Ten of 13 strains of F. avenaceum and 2 strains of F. poae and F. tricinctum produced beauvericin in culture on rice (trace to 70, 9.4, and 33 microg/g, respectively). All strains also produced enniatins (trace to 2,700 microg/g). This is the first report on the natural co-occurence of beauvericin and enniatins in wheat infected predominantly by F. avenaceum. PMID- 11772613 TI - Inoculation onto solid surfaces protects Salmonella spp. during acid challenge: a model study using polyethersulfone membranes. AB - Salmonellae are the most frequently reported cause of outbreaks of food-borne gastroenteritis in the United States. In clinical trials, the oral infective dose (ID) for healthy volunteers was estimated to be approximately 1 million cells. However, in reports from various outbreaks, the ID of Salmonella species associated with solid foods was estimated to be as few as 100 cells. We found that fresh-cut produce surfaces not only provided suitable solid support for pathogen attachment but also played a critical role in increasing the acid tolerance of the pathogen. However the acidic nature of certain produce played no role in making salmonellae resistant to stomach acidity. Inoculation onto fresh cut produce surfaces, as well as onto inert surfaces, such as polyethersulfone membranes and tissue paper, increased the survival of salmonellae during acid challenge (50 mM Na-citrate, pH 3.0; 37 degrees C; 2 h) by 4 to 5 log units. Acid challenge experiments using cells inoculated onto polyethersulfone membranes provided a model system suitable for studying the underlying fundamentals of the protection that occurs when Salmonella strains are associated with solid foods. The surface-associated acid protection, which was observed in several Salmonella strains, required de novo protein synthesis and was independent of stationary phase sigma transcription factor. PMID- 11772614 TI - Molecular characterization of a thermostable cyanophycin synthetase from the thermophilic cyanobacterium Synechococcus sp. strain MA19 and in vitro synthesis of cyanophycin and related polyamides. AB - The thermophilic cyanobacterium Synechococcus sp. strain MA19 contained the structural genes for cyanophycin synthetase (cphA) and cyanophycinase (cphB), which were identified, cloned, and sequenced in this study. The translation products of cphA and cphB exhibited high levels of similarity to corresponding proteins of other cyanobacteria, such as Anabaena variabilis and Synechocystis sp. Recombinant cells of Escherichia coli harboring cphA colinear with lacPO accumulated cyanophycin that accounted for up to 25% (wt/wt) of the dry cell matter in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG). The cyanophycin synthetase was enriched 123-fold to electrophoretic homogeneity from the soluble fraction of the recombinant cells by anion-exchange chromatography, affinity chromatography, and gel filtration chromatography. The purified cyanophycin synthetase maintained the parental thermophilic character and was active even after prolonged incubation at 50 degrees C; in the presence of ectoine the enzyme retained 90% of its activity even after 2 h of incubation. The in vitro activity of the enzyme depended on ATP, primers, and both substrates, L arginine and L-aspartic acid. In addition to native cyanophycin, the purified enzyme accepted a modified cyanophycin containing less arginine, alpha-arginyl aspartic acid dipeptide, and poly-alpha,beta-DL-aspartic acid as primers and also incorporated beta-hydroxyaspartic acid instead of L-aspartic acid or L-canavanine instead of L-arginine at a significant rate. The lack of specificity of this thermostable enzyme with respect to primers and substrates, the thermal stability of the enzyme, and the finding that the enzyme is suitable for in vitro production of cyanophycin make it an interesting candidate for biotechnological processes. PMID- 11772615 TI - Isolation and initial characterization of a bacterial consortium able to mineralize fluorobenzene. AB - Fluorinated compounds are known to be more resistant to microbial degradation than other halogenated chemicals. A microbial consortium capable of aerobic biodegradation of fluorobenzene (FB) as the sole source of carbon and energy was isolated by selective enrichment from sediments collected in a drain near an industrial site. A combination of three microbial strains recovered from the enriched consortium was shown to be necessary for complete FB mineralization. Two of the strains (F1 and F3) were classified by 16S rRNA analysis as belonging to the Sphingobacterium/Flavobacterium group, while the third (F4) falls in the beta Proteobacteria group, clustering with Alcaligenes species. Strain F4 was consistently found in the liquid cultures in a much greater proportion than strains F1 and F3 (86:8:6 for F4, F1, and F3, respectively). Stoichiometric release of fluoride ions was measured in batch and fed-batch cultures. In batch cultures, the consortium was able to use FB up to concentrations of 400 mg liter( 1) and was able to utilize a range of other organic compounds, including 4 fluorophenol and 4-fluorobenzoate. To our knowledge this is the first time biodegradation of FB as a sole carbon source has been reported. PMID- 11772616 TI - Role of the single regulator MrsR1 and the two-component system MrsR2/K2 in the regulation of mersacidin production and immunity. AB - The lantibiotic mersacidin is an antimicrobial peptide of 20 amino acids which inhibits bacterial cell wall biosynthesis by binding to the precursor molecule lipid II and which is produced by Bacillus sp. strain HIL Y-85,54728. The structural gene of mersacidin as well as accessory genes is organized in a biosynthetic gene cluster which is located on the chromosome and contains three open reading frames with similarities to regulatory proteins: mrsR2 and mrsK2 encode two proteins with homology to bacterial two-component systems, and mrsR1 shows similarity to a response regulator. Both mrsR2/K2 and mrsR1 were inactivated by insertion of an antibiotic resistance marker. Disruption of mrsR1 resulted in loss of mersacidin production; however, producer self-protection was not impaired. In contrast, inactivation of mrsR2/K2 led to an increased susceptibility to mersacidin whereas biosynthesis of the lantibiotic remained unaffected. Binding of mersacidin to intact cells was significantly enhanced in the mrsR2/K2 knockout mutant. Reverse transcription-PCR analysis from total RNA preparations showed that in contrast to the wild-type strain, the structural genes of the ABC transporter MrsFGE were not transcribed in the knockout mutant. It was therefore concluded that producer self-protection against mersacidin is conferred by the ABC transporter MrsFGE and that the transcription of mrsFGE is regulated by MrsR2/K2, whereas production of the antibacterial peptide is solely activated by MrsR1. PMID- 11772617 TI - Molecular diversity of Lactobacillus spp. and other lactic acid bacteria in the human intestine as determined by specific amplification of 16S ribosomal DNA. AB - A Lactobacillus group-specific PCR primer, S-G-Lab-0677-a-A-17, was developed to selectively amplify 16S ribosomal DNA (rDNA) from lactobacilli and related lactic acid bacteria, including members of the genera Leuconostoc, Pediococcus, and WEISSELLA: Amplicons generated by PCR from a variety of gastrointestinal (GI) tract samples, including those originating from feces and cecum, resulted predominantly in Lactobacillus-like sequences, of which ca. 28% were most similar to the 16S rDNA of Lactobacillus ruminis. Moreover, four sequences of Leuconostoc species were retrieved that, so far, have only been detected in environments other than the GI tract, such as fermented food products. The validity of the primer was further demonstrated by using Lactobacillus-specific PCR and denaturing gradient gel electrophoresis (DGGE) of the 16S rDNA amplicons of fecal and cecal origin from different age groups. The stability of the GI-tract bacterial community in different age groups over various time periods was studied. The Lactobacillus community in three adults over a 2-year period showed variation in composition and stability depending on the individual, while successional change of the Lactobacillus community was observed during the first 5 months of an infant's life. Furthermore, the specific PCR and DGGE approach was tested to study the retention in fecal samples of a Lactobacillus strain administered during a clinical trial. In conclusion, the combination of specific PCR and DGGE analysis of 16S rDNA amplicons allows the diversity of important groups of bacteria that are present in low numbers in specific ecosystems to be characterized, such as the lactobacilli in the human GI tract. PMID- 11772619 TI - Neurovirulence of type 1 polioviruses isolated from sewage in Japan. AB - Sixteen type 1 poliovirus strains were isolated from a sewage disposal plant located downstream of the Oyabe River in Japan between October 1993 and September 1995. The isolates were intratypically differentiated as vaccine-derived strains. Neutralizing antigenicity analysis with monoclonal antibodies and estimation of neurovirulence by mutant analysis by PCR and restriction enzyme cleavage (MAPREC) were performed for 13 type 1 strains of these isolates. The isolates were classified into three groups. Group I (five strains) had a variant type of antigenicity and neurovirulent phenotype. Group II (four strains) had the vaccine type of antigenicity and neurovirulent phenotype. Group III (four strains) had the vaccine type of antigenicity and an attenuated phenotype. Furthermore, it was demonstrated that the virulent isolates were neutralized by human sera obtained after oral poliomyelitis vaccine (OPV) administration, and the sera of rats immunized with inactivated poliovirus vaccine. Although vaccination was effective against virulent polioviruses, virulent viruses will continue to exist in the environment as long as OPV is in use. PMID- 11772618 TI - 16S rRNA-based analysis of microbiota from the cecum of broiler chickens. AB - The microbiota of the intestinal tract of chickens plays an important role in inhibiting the establishment of intestinal pathogens. Earlier culturing and microscopic examinations indicated that only a fraction of the bacteria in the cecum of chickens could be grown in the laboratory. Therefore, a survey of cecal bacteria was done by retrieval of 16S rRNA gene sequences from DNA isolated from the cecal content and the cecal mucosa. The ribosomal gene sequences were amplified with universal primers and cloned or subjected to temporal temperature gradient gel electrophoresis (TTGE). Partial 16S rRNA gene sequences were determined from the clones and from the major bands in TTGE gels. A total of 1,656 partial 16S rRNA gene sequences were obtained and compared to sequences in the GenBank. The comparison indicated that 243 different sequences were present in the samples. Overall, sequences representing 50 phylogenetic groups or subgroups of bacteria were found, but approximately 89% of the sequences represented just four phylogenetic groups (Clostridium leptum, Sporomusa sp., Clostridium coccoides, and enterics). Sequences of members of the Bacteroides group, the Bifidobacterium infantis subgroup, and of Pseudomonas sp. each accounted for less than 2% of the total. Sequences related to those from the Escherichia sp. subgroup and from Lactobacillus, Pseudomonas, and Bifidobacterium spp. were generally between 98 and 100% identical to sequences already deposited in the GenBank. Sequences most closely related to those of the other bacteria were generally 97% or less identical to those in the databases and therefore might be from currently unknown species. TTGE and random cloning indicated that certain phylogenetic subgroups were common to all birds analyzed, but sequence data from random cloning also provided evidence for qualitative and quantitative differences among the cecal microbiota of individual birds reared under very similar conditions. PMID- 11772620 TI - Elucidation of the flavonoid catabolism pathway in Pseudomonas putida PML2 by comparative metabolic profiling. AB - Flavonoids are 15-carbon plant secondary metabolites exuded in the rhizosphere that hosts several flavonoid-degrading bacteria. We studied flavonoid catabolism in a plant growth-promoting rhizobacterial strain of Pseudomonas by using a combination of biochemical and genetic approaches. Transposants carrying mini Tn5gfp insertions were screened for flavonoid auxotrophy, and these mutant strains were found to be unable to grow in the flavonols naringenin and quercetin, while their growth in glycerol was comparable to that of the parental strain. In order to understand flavonoid catabolism, culture supernatants, whole cell fractions, cell lysate, and cell debris of the wild-type and mutant strains were analyzed. Intermediates that accumulated intracellularly and those secreted in the medium were identified by a combination of reversed-phase high-pressure liquid chromatography and electrospray ionization-mass spectrometry. Structures of four key intermediates were confirmed by one-dimensional nuclear magnetic resonance spectroscopy. Comparative metabolic profiling of the compounds in the wild-type and mutant strains allowed us to understand the degradation events and to identify six metabolic intermediates. The first step in the pathway involves 3,3'-didehydroxylation, followed by hydrolysis and cleavage of the C-ring, leading via subsequent oxidations to the formation of protocatechuate. This is the first report on quercetin dehydroxylation in aerobic conditions leading to naringenin accumulation. PMID- 11772621 TI - Chimeric Vitreoscilla hemoglobin (VHb) carrying a flavoreductase domain relieves nitrosative stress in Escherichia coli: new insight into the functional role of VHb. AB - Dimeric hemoglobin (VHb) from the bacterium Vitreoscilla sp. strain C1 displays 30 to 53% sequence identity with the heme-binding domain of flavohemoglobins (flavoHbs) and exhibits the presence of potential sites for the interaction with its FAD/NADH reductase partner. The intersubunit contact region of VHb indicates a small interface between two monomers of the homodimer, suggesting that the VHb dimers may dissociate easily. Gel filtration chromatography of VHb exhibited a 25 to 30% monomeric population of VHb, at a low protein concentration (0.05 mg/ml), whereas dimeric VHb remained dominant at a high protein concentration (10 mg/ml). The structural characteristics of VHb suggest that the flavoreductase can also associate and interact with VHb in a manner analogous to flavoHbs and could yield a flavo-VHb complex. To unravel the functional relevance of the VHb-reductase association, the reductase domain of flavoHb from Ralstonia eutropha (formerly Alcaligenes eutrophus) was genetically engineered to generate a VHb-reductase chimera (VHb-R). The physiological implications of VHb and VHb-R were studied in an hmp mutant of Escherichia coli, incapable of producing any flavoHb. Cellular respiration the of the hmp mutant was instantaneously inhibited in the presence of 10 microM nitric oxide (NO) but remained insensitive to NO inhibition when these cells produced VHb-R. In addition, E. coli overproducing VHb-R exhibited NO consumption activity that was two to three times slower in cells overexpressing only VHb and totally undetectable in the control cells. A purified preparation of VHb-R exhibited a three- to fourfold-higher NADH-dependent NO uptake activity than that of VHb alone. Overproduction of VHb-R in the hmp mutant of E. coli conferred relief from the toxicity of sodium nitroprusside, whereas VHb alone provided only partial benefit under similar condition, suggesting that the association of VHb with reductase improves its capability to relieve the deleterious effect of nitrosative stress. Based on these results, it has been proposed that the unique structural features of VHb may allow it to acquire two functional states in vivo, namely, a single-domain homodimer that may participate in facilitated oxygen transfer or a two-domain heterodimer in association with its partner reductase that may be involved in modulating the cellular response under different environmental conditions. Due to this inherent structural flexibility, it may perform multiple functions in the cellular metabolism of its host. Separation of the oxidoreductase domain from VHb may thus provide a physiological advantage to its host. PMID- 11772622 TI - Occurrence of Cryptosporidium and Giardia in wild ducks along the Rio Grande River valley in southern New Mexico. AB - Fecal samples were taken from wild ducks on the lower Rio Grande River around Las Cruces, N. Mex., from September 2000 to January 2001. Giardia cysts and Cryptosporidium oocysts were purified from 69 samples by sucrose enrichment followed by cesium chloride (CsCl) gradient centrifugation and were viewed via fluorescent-antibody (FA) staining. For some samples, recovered cysts and oocysts were further screened via PCR to determine the presence of Giardia lamblia and Crytosporidium parvum. The results of this study indicate that 49% of the ducks were carriers of Cryptosporidium, and the Cryptosporidium oocyst concentrations ranged from 0 to 2,182 oocysts per g of feces (mean +/- standard deviation, 47.53 +/- 270.3 oocysts per g); also, 28% of the ducks were positive for Giardia, and the Giardia cyst concentrations ranged from 0 to 29,293 cysts per g of feces (mean +/- standard deviation, 436 +/- 3,525.4 cysts per g). Of the 69 samples, only 14 had (oo)cyst concentrations that were above the PCR detection limit. Samples did test positive for Cryptosporidium sp. However, C. parvum and G. lamblia were not detected in any of the 14 samples tested by PCR. Ducks on their southern migration through southern New Mexico were positive for Cryptosporidium and Giardia as determined by FA staining, but C. parvum and G. lamblia were not detected. PMID- 11772623 TI - Determination of key metabolites during biodegradation of hexahydro-1,3,5 trinitro-1,3,5-triazine with Rhodococcus sp. strain DN22. AB - Rhodococcus sp. strain DN22 can convert hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to nitrite, but information on degradation products or the fate of carbon is not known. The present study describes aerobic biodegradation of RDX (175 microM) when used as an N source for strain DN22. RDX was converted to nitrite (NO(2)(-)) (30%), nitrous oxide (N(2)O) (3.2%), ammonia (10%), and formaldehyde (HCHO) (27%), which later converted to carbon dioxide. In experiments with ring labeled [(15)N]-RDX, gas chromatographic/mass spectrophotometric (GC/MS) analysis revealed N(2)O with two molecular mass ions: one at 44 Da, corresponding to (14)N(14)NO, and the second at 45 Da, corresponding to (15)N(14)NO. The nonlabeled N(2)O could be formed only from -NO(2), whereas the (15)N-labeled one was presumed to originate from a nitramine group ((15)N-(14)NO(2)) in RDX. Liquid chromatographic (LC)-MS electrospray analyses indicated the formation of a dead end product with a deprotonated molecular mass ion [M-H] at 118 Da. High resolution MS indicated a molecular formula of C(2)H(5)N(3)O(3). When the experiment was repeated with ring-labeled [(15)N]-RDX, the [M-H] appeared at 120 Da, indicating that two of the three N atoms in the metabolite originated from the ring in RDX. When [U-(14)C]-RDX was used in the experiment, 64% of the original radioactivity in RDX incorporated into the metabolite with a molecular weight (MW) of 119 (high-pressure LC/radioactivity) and 30% in (14)CO(2) (mineralization) after 4 days of incubation, suggesting that one of the carbon atoms in RDX was converted to CO(2) and the other two were incorporated in the ring cleavage product with an MW of 119. Based on the above stoichiometry, we propose a degradation pathway for RDX based on initial denitration followed by ring cleavage to formaldehyde and the dead end product with an MW of 119. PMID- 11772624 TI - Isolation and characterization of Novosphingobium sp. strain MT1, a dominant polychlorophenol-degrading strain in a groundwater bioremediation system. AB - A high-rate fluidized-bed bioreactor has been treating polychlorophenol contaminated groundwater in southern Finland at 5 to 8 degrees C for over 6 years. We examined the microbial diversity of the bioreactor using three 16S ribosomal DNA (rDNA)-based methods: denaturing gradient gel electrophoresis, length heterogeneity-PCR analysis, and restriction fragment length polymorphism analysis. The molecular study revealed that the process was dependent on a stable bacterial community with low species diversity. The dominant organism, Novosphingobium sp. strain MT1, was isolated and characterized. Novosphingobium sp. strain MT1 degraded the main contaminants of the groundwater, 2,4,6 trichlorophenol, 2,3,4,6-tetrachlorophenol, and pentachlorophenol, at 8 degrees C. The strain carried a homolog of the pcpB gene, coding for the pentachlorophenol-4-monooxygenase in Sphingobium chlorophenolicum. Spontaneous deletion of the pcpB gene homolog resulted in the loss of degradation ability. Phenotypic dimorphism (planktonic and sessile phenotypes), low growth rate (0.14 to 0.15 h(-1)), and low-copy-number 16S rDNA genes (single copy) were characteristic of strain MT1 and other MT1-like organisms isolated from the bioreactor. PMID- 11772625 TI - Salmonella enterica serotype Bredeney: antimicrobial susceptibility and molecular diversity of isolates from Ireland and Northern Ireland. AB - Salmonella enterica serotype Bredeney has emerged as the third most commonly identified serotype among human clinical isolates referred to the Irish National Salmonella Reference Laboratory in the years 1998 to 2000. A collection of 112 isolates of S. enterica serotype Bredeney collected during the period 1995 to 1999 from animal, food, and human sources from both Ireland and Northern Ireland were studied. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and DNA amplification fingerprinting (DAF) were performed on all isolates. Plasmid profiles were examined on a subset of 33 isolates. A high proportion (74%) of isolates were susceptible to all antimicrobial agents tested. Resistance to both sulfonamide and trimethoprim was observed in 21% of isolates, and resistance to multiple (five) antimicrobial agents was observed in a single isolate (0.9%). Eight different PFGE patterns were obtained, with 87% of isolates grouping as PFGE type A. PFGE type A was predominant in animals, food, and humans. There was good overall concordance between the groups identified by PFGE and DAF. Overall results indicate that most S. enterica serotype Bredeney isolates in Ireland and Northern Ireland from animal and human sources are clonally related. PMID- 11772626 TI - Transfer of the pheromone-inducible plasmid pCF10 among Enterococcus faecalis microorganisms colonizing the intestine of mini-pigs. AB - A new animal model, the streptomycin-treated mini-pig, was developed in order to allow colonization of defined strains of Enterococcus faecalis in numbers sufficient to study plasmid transfer. Transfer of the pheromone-inducible pCF10 plasmid between streptomycin-resistant strains of E. faecalis OG1 was investigated in the model. The plasmid encodes resistance to tetracycline. Numbers of recipient, donor, and transconjugant bacteria were monitored by selective plating of fecal samples, and transconjugants were subsequently verified by PCR. After being ingested by the mini-pigs, the recipient strain persisted in the intestine at levels between 10(6) and 10(7) CFU per g of feces throughout the experiment. The donor strain, which carried different resistance markers but was otherwise chromosomally isogenic to the recipient strain, was given to the pigs 3 weeks after the recipient strain. The donor cells were initially present in high numbers (10(6) CFU per g) in feces, but they did not persist in the intestine at detectable levels. Immediately after introduction of the donor bacteria, transconjugant cells appeared and persisted in fecal samples at levels between 10(3) and 10(4) CFU per g until the end of the experiment. These observations showed that even in the absence of selective tetracycline pressure, plasmid pCF10 was transferred from ingested E. faecalis cells to other E. faecalis organisms already present in the intestinal environment and that the plasmid subsequently persisted in the intestine. PMID- 11772627 TI - Mutagenic analysis of a conserved region of domain III in the Cry1Ac toxin of Bacillus thuringiensis. AB - We used site-directed mutagenesis to probe the function of four alternating arginines located at amino acid positions 525, 527, 529, and 531 in a highly conserved region of domain III in the Cry1Ac toxin of Bacillus thuringiensis. We created 10 mutants: eight single mutants, with each arginine replaced by either glycine (G) or aspartic acid (D), and two double mutants (R525G/R527G and R529G/R531G). In lawn assays of the 10 mutants with a cultured Choristoneura fumiferana insect cell line (Cf1), replacement of a single arginine by either glycine or aspartic acid at position 525 or 529 decreased toxicity 4- to 12-fold relative to native Cry1Ac toxin, whereas replacement at position 527 or 531 decreased toxicity only 3-fold. The reduction in toxicity seen with double mutants was 8-fold for R525G/R527G and 25-fold for R529G/R531G. Five of the mutants (R525G, R525D, R527G, R529D, and R525G/R527G) were tested in bioassays with Plutella xylostella larvae and ion channel formation in planar lipid bilayers. In the bioassays, R525D, R529D, and R525G/R527G showed reduced toxicity. In planar lipid bilayers, the conductance and the selectivity of the mutants were similar to those of native Cry1Ac. Toxins with alteration at position 527 or 529 tended to remain in their subconducting states rather than the maximally conducting state. Our results suggest that the primary role of this conserved region is to maintain both the structural integrity of the native toxin and the full functionality of the formed membrane pore. PMID- 11772628 TI - New degenerate Cytophaga-Flexibacter-Bacteroides-specific 16S ribosomal DNA targeted oligonucleotide probes reveal high bacterial diversity in River Taff epilithon. AB - River microbial communities play an important role in global nutrient cycles, and aggregated bacteria such as those in epilithic biofilms may be major contributors. In this study the bacterial diversity of River Taff epilithon in South Wales was investigated. A 16S ribosomal DNA (rDNA) clone library was constructed and analyzed by partial sequencing of 76 of 347 clones and hybridization with taxon-specific probes. The epilithon was found to be very diverse, with an estimated 59.6% of the bacterial populations not accounted for by these clones. Members of the Cytophaga-Flexibacter-Bacteroides division (CFBs) were most abundant in the library, representing 25% of clones, followed by members of the alpha subdivision of the division Proteobacteria (alpha Proteobacteria), gamma-Proteobacteria, gram-positive bacteria, Cyanobacteria, beta-Proteobacteria, delta-Proteobacteria, and the Prosthecobacter group. This study concentrated on the epilithic CFB populations, and a new set of degenerate 16S rDNA probes was developed to enhance their detection, namely, CFB560, CFB562, and CFB376. The commonly used probe CF319a/b may frequently lead to the underestimation of CFB populations in environmental studies, because it does not fully detect members of the division. CFB560 had exact matches to 95.6% of CFBs listed in the Ribosomal Database Project (release 8.0) small-subunit phylogenetic trees, compared to 60% for CF319a/b. The CFB probes detected 66 of 347 epilithon TAF clones, and 60 of these were partially sequenced. They affiliated with the RDP-designated groups Cytophaga, Sphingobacterium, Lewinella, and Cytophaga aurantiaca. CFB560 and CF319a/b detected 94% (62 of 66) and 48.5% (32 of 66) of clones, respectively, and therefore CFB560 is recommended for future use. Probe design in this study illustrated that multiple degenerate positions can greatly increase target range without adversely effecting specificity or experimental performance. PMID- 11772629 TI - Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding an alpha-amino acid ester hydrolase from Acetobacter turbidans. AB - The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is capable of hydrolyzing and synthesizing beta-lactam antibiotics, such as cephalexin and ampicillin. N-terminal amino acid sequencing of the purified alpha amino acid ester hydrolase allowed cloning and genetic characterization of the corresponding gene from an A. turbidans genomic library. The gene, designated aehA, encodes a polypeptide with a molecular weight of 72,000. Comparison of the determined N-terminal sequence and the deduced amino acid sequence indicated the presence of an N-terminal leader sequence of 40 amino acids. The aehA gene was subcloned in the pET9 expression plasmid and expressed in Escherichia coli. The recombinant protein was purified and found to be dimeric with subunits of 70 kDa. A sequence similarity search revealed 26% identity with a glutaryl 7-ACA acylase precursor from Bacillus laterosporus, but no homology was found with other known penicillin or cephalosporin acylases. There was some similarity to serine proteases, including the conservation of the active site motif, GXSYXG. Together with database searches, this suggested that the alpha-amino acid ester hydrolase is a beta-lactam antibiotic acylase that belongs to a class of hydrolases that is different from the Ntn hydrolase superfamily to which the well-characterized penicillin acylase from E. coli belongs. The alpha-amino acid ester hydrolase of A. turbidans represents a subclass of this new class of beta-lactam antibiotic acylases. PMID- 11772630 TI - Molecular monitoring of succession of bacterial communities in human neonates. AB - The establishment of bacterial communities in two healthy babies was examined for more than the first 10 months of life by monitoring 16S ribosomal DNA (rDNA) diversity in fecal samples by PCR and denaturing gradient gel electrophoresis (DGGE) and by analyzing the sequences of the major ribotypes. DGGE profiles of the dominant populations in the intestines of the infants were obtained by analyzing daily or weekly fecal samples. After delivery, the germfree infant gastrointestinal tracts were rapidly colonized, and the succession of bacteria in each ecosystem was monitored. During the first few days of life the profiles were simple, but they became more complex as the bacterial diversity increased with time in both babies. Clone libraries of amplified 16S rDNA fragments from baby feces were constructed, and these libraries allowed identification of the bacterial types by comparative DNA sequence analysis; the bacteria identified included members of the genera Bifidobacterium, Ruminococcus, Enterococcus, Clostridium, and Enterobacter: Species most closely related to the genera Bifidobacterium and Ruminococcus in particular dominated the intestinal microbiota based on the stability over time and the numbers, as estimated by the intensities of the bands. However, 19 of the 34 cloned rDNA sequences exhibited less than 97% identity with sequences of known bacteria or cloned sequences in databases. This study showed that using PCR-DGGE and 16S rDNA sequence analysis together resulted in a dynamic description of bacterial colonization in the infant intestinal ecosystem and allowed visualization of bacteria that are difficult to cultivate or to detect by other methods. PMID- 11772631 TI - Optimization of the cell wall microenvironment allows increased production of recombinant Bacillus anthracis protective antigen from B. subtilis. AB - The stability of heterologous proteins secreted by gram-positive bacteria is greatly influenced by the microenvironment on the trans side of the cytoplasmic membrane, and secreted heterologous proteins are susceptible to rapid degradation by host cell proteases. In Bacillus subtilis, degradation occurs either as the proteins emerge from the presecretory translocase and prior to folding into their native conformation or after the native conformation has been reached. The former process generally involves membrane- and/or cell wall-bound proteases, while the latter involves proteases that are released into the culture medium. The identification and manipulation of factors that influence the folding of heterologous proteins has the potential to improve the yield of secreted heterologous proteins. Recombinant anthrax protective antigen (rPA) has been used as a model secreted heterologous protein because it is sensitive to proteolytic degradation both before and after folding into its native conformation. This paper describes the influence of the microenvironment on the trans side of the cytoplasmic membrane on the stability of rPA. Specifically, we have determined the influence of net cell wall charge and its modulation by the extent to which the anionic polymer teichoic acid is D-alanylated on the secretion and stability of rPA. The potential role of the dlt operon, responsible for D-alanylation, was investigated using a Bacillus subtilis strain encoding an inducible dlt operon. We show that, in the absence of D-alanylation, the yield of secreted rPA is increased 2.5-fold. The function of D-alanylation and the use of rPA as a model protein are evaluated with respect to the optimization of B. subtilis for the secretion of heterologous proteins. PMID- 11772632 TI - Single-base-pair discrimination of terminal mismatches by using oligonucleotide microarrays and neural network analyses. AB - The effects of single-base-pair near-terminal and terminal mismatches on the dissociation temperature (T(d)) and signal intensity of short DNA duplexes were determined by using oligonucleotide microarrays and neural network (NN) analyses. Two perfect-match probes and 29 probes having a single-base-pair mismatch at positions 1 to 5 from the 5' terminus of the probe were designed to target one of two short sequences representing 16S rRNA. Nonequilibrium dissociation rates (i.e., melting profiles) of all probe-target duplexes were determined simultaneously. Analysis of variance revealed that position of the mismatch, type of mismatch, and formamide concentration significantly affected the T(d) and signal intensity. Increasing the concentration of formamide in the washing buffer decreased the T(d) and signal intensity, and it decreased the variability of the signal. Although T(d)s of probe-target duplexes with mismatches in the first or second position were not significantly different from one another, duplexes with mismatches in the third to fifth positions had significantly lower T(d)s than those with mismatches in the first or second position. The trained NNs predicted the T(d) with high accuracies (R(2) = 0.93). However, the NNs predicted the signal intensity only moderately accurately (R(2) = 0.67), presumably due to increased noise in the signal intensity at low formamide concentrations. Sensitivity analysis revealed that the concentration of formamide explained most (75%) of the variability in T(d)s, followed by position of the mismatch (19%) and type of mismatch (6%). The results suggest that position of the mismatch at or near the 5' terminus plays a greater role in determining the T(d) and signal intensity of duplexes than the type of mismatch. PMID- 11772633 TI - Quantification of Nitrosomonas oligotropha-like ammonia-oxidizing bacteria and Nitrospira spp. from full-scale wastewater treatment plants by competitive PCR. AB - Utilizing the principle of competitive PCR, we developed two assays to enumerate Nitrosomonas oligotropha-like ammonia-oxidizing bacteria and nitrite-oxidizing bacteria belonging to the genus NITROSPIRA: The specificities of two primer sets, which were designed for two target regions, the amoA gene and Nitrospira 16S ribosomal DNA (rDNA), were verified by DNA sequencing. Both assays were optimized and applied to full-scale, activated sludge wastewater treatment plant (WWTP) samples. If it was assumed that there was an average of 3.6 copies of 16S rDNA per cell in the total population and two copies of the amoA gene per ammonia oxidizing bacterial cell, the ammonia oxidizers examined represented 0.0033% +/- 0.0022% of the total bacterial population in a municipal WWTP. N. oligotropha like ammonia-oxidizing bacteria were not detected in an industrial WWTP. If it was assumed that there was one copy of the 16S rDNA gene per nitrite-oxidizing bacterial cell, Nitrospira spp. represented 0.39% +/- 0.28% of the biosludge population in the municipal WWTP and 0.37% +/- 0.23% of the population in the industrial WWTP. The number of Nitrospira sp. cells in the municipal WWTP was more than 62 times greater than the number of N. oligotropha-like cells, based on a competitive PCR analysis. The results of this study extended our knowledge of the comparative compositions of nitrifying bacterial populations in wastewater treatment systems. Importantly, they also demonstrated that we were able to quantify these populations, which ultimately will be required for accurate prediction of process performance and stability for cost-effective design and operation of WWTPs. PMID- 11772634 TI - Cloning and expression of an oligopeptidase, PepO, with novel specificity from Lactobacillus rhamnosus HN001 (DR20). AB - Oligopeptidases of starter and nonstarter lactic acid bacteria contribute to the proteolytic events important in maturation and flavor development processes in cheese. This paper describes the molecular cloning, expression, and specificity of the oligopeptidase PepO from the probiotic nonstarter strain Lactobacillus rhamnosus HN001 (DR20). The pepO gene encodes a protein of 70.9 kDa, whose primary sequence includes the HEXXH motif present in certain classes of metallo oligopeptidases. The pepO gene was cloned in L. rhamnosus HN001 and overexpressed in pTRKH2 from its own promoter, which was mapped by primer extension. It was further cloned in both pNZ8020 and pNZ8037 and overexpressed in Lactococcus lactis subsp. cremoris NZ9000 from the nisA promoter. The purified PepO enzyme demonstrated unique cleavage specificity for alpha(s1)-casein fragment 1-23, hydrolyzing the bonds Pro-5-Ile-6, Lys-7-His-8, His-8-Gln-9, and Gln-9-Gly-10. The impact of this enzyme in cheese can now be assessed. PMID- 11772635 TI - Identification and characterization of the gene cluster involved in chitin degradation in a marine bacterium, Alteromonas sp. strain O-7. AB - Alteromonas sp. strain O-7 secretes chitinase A (ChiA), chitinase B (ChiB), and chitinase C (ChiC) in the presence of chitin. A gene cluster involved in the chitinolytic system of the strain was cloned and sequenced upstream of and including the chiA gene. The gene cluster consisted of three different open reading frames organized in the order chiD, cbp1, and chiA. The chiD, cbp1, and chiA genes were closely linked and transcribed in the same direction. Sequence analysis indicated that Cbp1 (475 amino acids) was a chitin-binding protein composed of two discrete functional regions. ChiD (1,037 amino acids) showed sequence similarity to bacterial chitinases classified into family 18 of glycosyl hydrolases. The cbp1 and chiD genes were expressed in Escherichia coli, and the recombinant proteins were purified to homogeneity. The highest binding activities of Cbp1 and ChiD were observed when alpha-chitin was used as a substrate. Cbp1 and ChiD possessed a chitin-binding domain (ChtBD) belonging to ChtBD type 3. ChiD rapidly hydrolyzed chitin oligosaccharides in sizes from trimers to hexamers, but not chitin. However, after prolonged incubation with large amounts of ChiD, the enzyme produced a small amount of (GlcNAc)(2) from chitin. The optimum temperature and pH of ChiD were 50 degrees C and 7.0, respectively. PMID- 11772636 TI - Identification of the 2-methylcitrate pathway involved in the catabolism of propionate in the polyhydroxyalkanoate-producing strain Burkholderia sacchari IPT101(T) and analysis of a mutant accumulating a copolyester with higher 3 hydroxyvalerate content. AB - Burkholderia sacchari IPT101(T) induced the formation of 2-methylcitrate synthase and 2-methylisocitrate lyase when it was cultivated in the presence of propionic acid. The prp locus of B. sacchari IPT101(T) is required for utilization of propionic acid as a sole carbon source and is relevant for incorporation of 3 hydroxyvalerate (3HV) into copolyesters, and it was cloned and sequenced. Five genes (prpR, prpB, prpC, acnM, and ORF5) exhibited identity to genes located in the prp loci of other gram-negative bacteria. prpC encodes a 2-methylcitrate synthase with a calculated molecular mass of 42,691 Da. prpB encodes a 2 methylisocitrate lyase. The levels of PrpC and PrpB activity were much lower in propionate-negative mutant IPT189 obtained from IPT101(T) and were heterologously expressed in Escherichia coli. The acnM gene (ORF4) and ORF5, which are required for conversion of 2-methylcitric acid to 2-methylisocitric acid in Ralstonia eutropha HF39, are also located in the prp locus. The translational product of ORF1 (prpR) had a calculated molecular mass of 70,598 Da and is a putative regulator of the prp cluster. Three additional open reading frames (ORF6, ORF7, and ORF8) whose functions are not known were located adjacent to ORF5 in the prp locus of B. sacchari, and these open reading frames have not been found in any other prp operon yet. In summary, the organization of the prp genes of B. sacchari is similar but not identical to the organization of these genes in other bacteria investigated recently. In addition, this study provided a rationale for the previously shown increased molar contents of 3HV in copolyesters accumulated by a B. sacchari mutant since it was revealed in this study that the mutant is defective in prpC. PMID- 11772637 TI - Homology of Escherichia coli R773 arsA, arsB, and arsC genes in arsenic-resistant bacteria isolated from raw sewage and arsenic-enriched creek waters. AB - The occurrence and diversity of the Escherichia coli R773 ars operon were investigated among arsenic-resistant enteric and nonenteric bacteria isolated from raw sewage and arsenic-enriched creek waters. Selected isolates from each creek location were screened for ars genes by colony hybridization and PCR. The occurrence of arsA, arsB, and arsC determined by low-stringency colony hybridization (31 to 53% estimated mismatch) was 81, 87, and 86%, respectively, for 84 bacteria isolated on arsenate- and arsenite-amended media from three locations. At moderate stringency (21 to 36% estimated mismatch), the occurrence decreased to 42, 56, and 63% for arsA, arsB, and arsC, respectively. PCR results showed that the ars operon is conserved in some enteric bacteria isolated from creek waters and raw sewage. The occurrence of the arsBC genotype was about 50% in raw sewage enteric bacteria, while arsA was detected in only 9.4% of the isolates (n = 32). The arsABC and arsBC genotypes occurred more frequently in enteric bacteria isolated from creek samples: 71.4 and 85.7% (n = 7), respectively. Average sequence divergence within arsB for six creek enteric bacteria was 20% compared to that of the E. coli R773 ars operon. Only 1 of 11 pseudomonads screened by PCR was positive for arsB. The results from this study suggest that significant divergence has occurred in the ars operon among As resistant E. coli strains and in Pseudomonas spp. PMID- 11772638 TI - Duplicate copies of genes encoding methanesulfonate monooxygenase in Marinosulfonomonas methylotropha strain TR3 and detection of methanesulfonate utilizers in the environment. AB - Marinosulfonomonas methylotropha strain TR3 is a marine methylotroph that uses methanesulfonic acid (MSA) as a sole carbon and energy source. The genes from M. methylotropha strain TR3 encoding methanesulfonate monooxygenase, the enzyme responsible for the initial oxidation of MSA to formaldehyde and sulfite, were cloned and sequenced. They were located on two gene clusters on the chromosome of this bacterium. A 5.0-kbp HindIII fragment contained msmA, msmB, and msmC, encoding the large and small subunits of the hydroxylase component and the ferredoxin component, respectively, of the methanesulfonate monooxygenase, while a 6.5-kbp HindIII fragment contained duplicate copies of msmA and msmB, as well as msmD, encoding the reductase component of methanesulfonate. Both sets of msmA and msmB genes were virtually identical, and the derived msmA and msmB sequences of M. methylotropha strain TR3, compared with the corresponding hydroxylase from the terrestrial MSA utilizer Methylosulfonomonas methylovora strain M2 were found to be 82 and 69% identical. The msmA gene was investigated as a functional gene probe for detection of MSA-utilizing bacteria. PCR primers spanning a region of msmA which encoded a unique Rieske [2Fe-2S] binding region were designed. These primers were used to amplify the corresponding msmA genes from newly isolated Hyphomicrobium, Methylobacterium, and Pedomicrobium species that utilized MSA, from MSA enrichment cultures, and from DNA samples extracted directly from the environment. The high degree of identity of these msmA gene fragments, compared to msmA sequences from extant MSA utilizers, indicated the effectiveness of these PCR primers in molecular microbial ecology. PMID- 11772639 TI - Evolution of the lactic acid bacterial community during malt whisky fermentation: a polyphasic study. AB - The development of the lactic acid bacterial community in a commercial malt whisky fermentation occurred in three broad phases. Initially, bacteria were inhibited by strong yeast growth. Fluorescence microscopy and environmental scanning electron microscopy revealed, in this early stage, both cocci and rods that were at least partly derived from the wort and yeast but also stemmed from the distillery plant. Denaturing gradient gel electrophoresis (DGGE) of partial 16S rRNA genes and sequence analysis revealed cocci related to Streptococcus thermophilus or Saccharococcus thermophilus, Lactobacillus brevis, and Lactobacillus fermentum. The middle phase began 35 to 40 h after yeast inoculation and was characterized by exponential growth of lactobacilli and residual yeast metabolism. Lactobacillus casei or Lactobacillus paracasei, L. fermentum, and Lactobacillus ferintoshensis were detected in samples of fermenting wort examined by DGGE during this stage. Bacterial growth was accompanied by the accumulation of acetic and lactic acids and the metabolism of residual maltooligosaccharides. By 70 h, two new PCR bands were detected on DGGE gels, and the associated bacteria were largely responsible for the final phase of the fermentation. The bacteria were phylogenetically related to Lactobacillus acidophilus and Lactobacillus delbrueckii, and strains similar to the former had previously been recovered from malt whisky fermentations in Japan. These were probably obligately homofermentative bacteria, required malt wort for growth, and could not be cultured on normal laboratory media, such as MRS. Their metabolism during the last 20 to 30 h of fermentation was associated with yeast death and autolysis and further accumulation of lactate but no additional acetate. PMID- 11772640 TI - Chromosomal location plays a role in regulation of aflatoxin gene expression in Aspergillus parasiticus. AB - The nor-1 gene in the filamentous fungus Aspergillus parasiticus encodes a ketoreductase involved in aflatoxin biosynthesis. To study environmental influences on nor-1 expression, we generated plasmid pAPGUSNNB containing a nor-1 promoter-beta-glucuronidase (GUS) (encoded by uidA) reporter fusion with niaD (encodes nitrate reductase) as a selectable marker. niaD transformants of A. parasiticus strain NR-1 (niaD) carried pAPGUSNNB integrated predominantly at the nor-1 or niaD locus. Expression of the native nor-1 and nor-1::GUS reporter was compared in transformants grown under aflatoxin-inducing conditions by Northern and Western analyses and by qualitative and quantitative GUS activity assays. The timing and level of nor-1 promoter function with pAPGUSNNB integrated at nor-1 was similar to that observed for the native nor-1 gene. In contrast, nor-1 promoter activity in pAPGUSNNB and a second nor-1::GUS reporter construct, pBNG3.0, was not detectable when integration occurred at niaD. Because niaD dependent regulation could account for the absence of expression at niaD, a third chromosomal location was analyzed using pAPGUSNP, which contained nor-1::GUS plus pyrG (encodes OMP decarboxylase) as a selectable marker. GUS expression was detectable only when pAPGUSNP integrated at nor-1 and was not detectable at pyrG, even under growth conditions that required pyrG expression. nor-1::GUS is regulated similarly to the native nor-1 gene when it is integrated at its homologous site within the aflatoxin gene cluster but is not expressed at native nor-1 levels at two locations outside of the aflatoxin gene cluster. We conclude that the GUS reporter system can be used effectively to measure nor-1 promoter activity and that nor-1 is subject to position-dependent regulation in the A. parasiticus chromosome. PMID- 11772641 TI - Characterization of an autotrophic sulfide-oxidizing marine Arcobacter sp. that produces filamentous sulfur. AB - A coastal marine sulfide-oxidizing autotrophic bacterium produces hydrophilic filamentous sulfur as a novel metabolic end product. Phylogenetic analysis placed the organism in the genus Arcobacter in the epsilon subdivision of the Proteobacteria. This motile vibrioid organism can be considered difficult to grow, preferring to grow under microaerophilic conditions in flowing systems in which a sulfide-oxygen gradient has been established. Purified cell cultures were maintained by using this approach. Essentially all 4',6-diamidino-2-phenylindole dihydrochloride-stained cells in a flowing reactor system hybridized with Arcobacter-specific probes as well as with a probe specific for the sequence obtained from reactor-grown cells. The proposed provisional name for the coastal isolate is "Candidatus Arcobacter sulfidicus." For cells cultured in a flowing reactor system, the sulfide optimum was higher than and the CO(2) fixation activity was as high as or higher than those reported for other sulfur oxidizers, such as Thiomicrospira spp. Cells associated with filamentous sulfur material demonstrated nitrogen fixation capability. No ribulose 1,5-bisphosphate carboxylase/oxygenase could be detected on the basis of radioisotopic activity or by Western blotting techniques, suggesting an alternative pathway of CO(2) fixation. The process of microbial filamentous sulfur formation has been documented in a number of marine environments where both sulfide and oxygen are available. Filamentous sulfur formation by "Candidatus Arcobacter sulfidicus" or similar strains may be an ecologically important process, contributing significantly to primary production in such environments. PMID- 11772642 TI - Spatial and resource factors influencing high microbial diversity in soil. AB - To begin defining the key determinants that drive microbial community structure in soil, we examined 29 soil samples from four geographically distinct locations taken from the surface, vadose zone, and saturated subsurface using a small subunit rRNA-based cloning approach. While microbial communities in low-carbon, saturated, subsurface soils showed dominance, microbial communities in low-carbon surface soils showed remarkably uniform distributions, and all species were equally abundant. Two diversity indices, the reciprocal of Simpson's index (1/D) and the log series index, effectively distinguished between the dominant and uniform diversity patterns. For example, the uniform profiles characteristic of the surface communities had diversity index values that were 2 to 3 orders of magnitude greater than those for the high-dominance, saturated, subsurface communities. In a site richer in organic carbon, microbial communities consistently exhibited the uniform distribution pattern regardless of soil water content and depth. The uniform distribution implies that competition does not shape the structure of these microbial communities. Theoretical studies based on mathematical modeling suggested that spatial isolation could limit competition in surface soils, thereby supporting the high diversity and a uniform community structure. Carbon resource heterogeneity may explain the uniform diversity patterns observed in the high-carbon samples even in the saturated zone. Very high levels of chromium contamination (e.g., >20%) in the high-organic-matter soils did not greatly reduce the diversity. Understanding mechanisms that may control community structure, such as spatial isolation, has important implications for preservation of biodiversity, management of microbial communities for bioremediation, biocontrol of root diseases, and improved soil fertility. PMID- 11772643 TI - Comparative genomic analysis of archaeal genotypic variants in a single population and in two different oceanic provinces. AB - Planktonic crenarchaeotes are present in high abundance in Antarctic winter surface waters, and they also make up a large proportion of total cell numbers throughout deep ocean waters. To better characterize these uncultivated marine crenarchaeotes, we analyzed large genome fragments from individuals recovered from a single Antarctic picoplankton population and compared them to those from a representative obtained from deeper waters of the temperate North Pacific. Sequencing and analysis of the entire DNA insert from one Antarctic marine archaeon (fosmid 74A4) revealed differences in genome structure and content between Antarctic surface water and temperate deepwater archaea. Analysis of the predicted gene products encoded by the 74A4 sequence and those derived from a temperate, deepwater planktonic crenarchaeote (fosmid 4B7) revealed many typical archaeal proteins but also several proteins that so far have not been detected in archaea. The unique fraction of marine archaeal genes included, among others, those for a predicted RNA-binding protein of the bacterial cold shock family and a eukaryote-type Zn finger protein. Comparison of closely related archaea originating from a single population revealed significant genomic divergence that was not evident from 16S rRNA sequence variation. The data suggest that considerable functional diversity may exist within single populations of coexisting microbial strains, even those with identical 16S rRNA sequences. Our results also demonstrate that genomic approaches can provide high-resolution information relevant to microbial population genetics, ecology, and evolution, even for microbes that have not yet been cultivated. PMID- 11772644 TI - Molecular characterization of novel red green nonsulfur bacteria from five distinct hot spring communities in Yellowstone National Park. AB - We characterized and compared five geographically isolated hot springs with distinct red-layer communities in Yellowstone National Park. Individual red-layer communities were observed to thrive in temperatures ranging from 35 to 60 degrees C and at pH 7 to 9. All communities were dominated by red filamentous bacteria and contained bacteriochlorophyll a (Bchl a), suggesting that they represented novel green nonsulfur (GNS) bacteria. The in vivo absorption spectra of individual sites were different, with two sites showing unusual Bchl a protein absorption bands beyond 900 nm. We prepared and analyzed 16S rRNA libraries from all of these sites by using a combination of general bacterial primers and new GNS-specific primers described here. These studies confirmed the presence of novel GNS-like bacteria in all five communities. All GNS-like clones were most similar to Roseiflexus castenholzii, a red filamentous bacterium from Japan that also contains only Bchl a. Phylogenies constructed by using GNS-like clones from Yellowstone red-layer communities suggest the presence of a moderately diverse new "red" cluster within the GNS lineage. Within this cluster, at least two well supported subclusters emerged: YRL-A was most similar to Roseiflexus and YRL-B appeared to be novel, containing no known isolates. While these patterns showed some site specificity, they did not correlate with observed Bchl a spectrum differences or obvious features of the habitat. PMID- 11772645 TI - Phylogenetic identification and substrate uptake patterns of sulfate-reducing bacteria inhabiting an oxic-anoxic sewer biofilm determined by combining microautoradiography and fluorescent in situ hybridization. AB - We simultaneously determined the phylogenetic identification and substrate uptake patterns of sulfate-reducing bacteria (SRB) inhabiting a sewer biofilm with oxygen, nitrate, or sulfate as an electron acceptor by combining microautoradiography and fluorescent in situ hybridization (MAR-FISH) with family and genus-specific 16S rRNA probes. The MAR-FISH analysis revealed that Desulfobulbus hybridized with probe 660 was a dominant SRB subgroup in this sewer biofilm, accounting for 23% of the total SRB. Approximately 9 and 27% of Desulfobulbus cells detected with probe 660 could take up [(14)C]propionate with oxygen and nitrate, respectively, as an electron acceptor, which might explain the high abundance of this species in various oxic environments. Furthermore, more than 40% of Desulfobulbus cells incorporated acetate under anoxic conditions. SRB were also numerically important members of H(2)-utilizing and (14)CO(2)-fixing microbial populations in this sewer biofilm, accounting for roughly 42% of total H(2)-utilizing bacteria hybridized with probe EUB338. A comparative 16S ribosomal DNA analysis revealed that two SRB populations, related to the Desulfomicrobium hypogeium and the Desulfovibrio desulfuricans MB lineages, were found to be important H(2) utilizers in this biofilm. The substrate uptake characteristics of different phylogenetic SRB subgroups were compared with the characteristics described to date. These results provide further insight into the correlation between the 16S rRNA phylogenetic diversity and the physiological diversity of SRB populations inhabiting sewer biofilms. PMID- 11772646 TI - Identification of a gene essential for sheathed structure formation in Sphaerotilus natans, a filamentous sheathed bacterium. AB - Sphaerotilus natans, a filamentous bacterium that causes bulking in activated sludge processes, can assume two distinct morphologies, depending on the substrate concentration for growth; in substrate-rich media it grows as single rod-shaped cells, whereas in substrate-limited media it grows as filaments. To identify genes responsible for sheath formation, we carried out transposon Tn5 mutagenesis. Of the approximately 20,000 mutants obtained, 7 did not form sheathed structures. Sequencing of the Tn5-flanking regions showed that five of the seven Tn5 insertions converged at the same open reading frame, designated sthA. The deduced amino acids encoded by sthA were found to be homologous to glycosyltransferase, which is known to be involved in linking sugars to lipid carriers during bacterial exopolysaccharide biosynthesis. Disruption of the gene of the wild-type strain by inserting a kanamycin resistance gene cassette also resulted in sheathless growth under either type of nutrient condition. These findings indicate that sthA is a crucial component responsible for sheath formation. PMID- 11772647 TI - Identification and characterization of a putative transcriptional regulator controlling the expression of fouling inhibitors in Pseudoalteromonas tunicata. AB - The dark green pigmented marine bacterium Pseudoalteromonas tunicata colonizes living surfaces and produces a range of extracellular compounds that inhibit common fouling organisms, including marine invertebrate larvae, algae, bacteria, and fungi. We have observed a positive correlation between the antifouling activity of P. tunicata strain D2 and the expression of pigmentation. To address the hypothesis that pigmentation and antifouling may be jointly regulated in this organism and to begin to identify potential regulatory elements, we used transposon mutagenesis to generate a strain of P. tunicata deficient in antifouling activity. The data presented here describe the phenotypic and molecular characterization of a nonpigmented transposon mutant strain of P. tunicata (D2W2). Analyses of the antifouling capabilities of D2W2 demonstrate that this strain is deficient in the ability to inhibit each of the target fouling organisms. Genetic analysis of D2W2 identified a gene, designated wmpR (white mutant phenotype), with high sequence similarity to transcriptional regulators ToxR from Vibrio cholerae and CadC from Escherichia coli. Two dimensional polyacrylamide gel electrophoresis analysis revealed that WmpR is essential for the expression of a significant subset of stationary-phase-induced proteins likely to be important for the synthesis of fouling inhibitors. The identification of a gene involved in the regulation of expression of antifouling phenotypes will contribute to the understanding of the interactions between bacteria and other surface-colonizing organisms in the marine environment. PMID- 11772648 TI - Phylogeny of culturable estuarine bacteria catabolizing riverine organic matter in the northern Baltic Sea. AB - The objective of our study was to isolate and determine the phylogenetic affiliation of culturable estuarine bacteria capable of catabolizing riverine dissolved organic matter (RDOM) under laboratory conditions. Additions of RDOM consistently promoted the growth of estuarine bacteria in carbon-limited dilution cultures, with seasonal variation in growth rates and yields. At least 42 different taxa were culturable on solid agar media and, according to quantitative DNA-DNA hybridizations, constituted 32 to 89% of the total bacterial number in the enriched treatments. Five species in the Cytophaga-Flexibacter-Bacteroides group and one in the gamma-proteobacteria phylogenetic group (Marinomonas sp.) were numerically dominant during the stationary phase of the RDOM-enriched dilution cultures but not in the control cultures. Four of the isolates in Cytophaga-Flexibacter-Bacteroides group were putatively affiliated with the genus FLAVOBACTERIUM: All dominating isolates were determined to be new species based on comparison to the current databases. The same group of species dominated independently of the season investigated, suggesting a low diversity of bacteria catabolizing RDOM in the estuary. It also suggested a broad tolerance of the dominating species to seasonal variation in hydrography, chemistry, and competition with other species. Taken together, our results suggest that a limited group of bacteria, mainly in the Flavobacterium genus, played an important role in introducing new energy and carbon to the marine system in the northern Baltic Sea. PMID- 11772649 TI - Capsule-transmitted gut symbiotic bacterium of the Japanese common plataspid stinkbug, Megacopta punctatissima. AB - The Japanese common plataspid stinkbug, Megacopta punctatissima, deposits small brown particles, or symbiont capsules, on the underside of the egg mass for the purpose of transmission of symbiotic bacteria to the offspring. We investigated the microbiological aspects of the bacteria contained in the capsule, such as microbial diversity, phylogenetic placement, localization in vivo, and fitness effects on the host insect. Restriction fragment length polymorphism analysis of 16S ribosomal DNA clones revealed that a single bacterial species dominates the microbiota in the capsule. The bacterium was not detected in the eggs but in the capsules, which unequivocally demonstrated that the bacterium is transmitted to the offspring of the insect orally rather than transovarially, through probing of the capsule content. Molecular phylogenetic analysis showed that the bacterium belongs to the gamma-subdivision of the Proteobacteria. In adult insects the bacterium was localized in the posterior section of the midgut. Deprivation of the bacterium from the nymphs resulted in retarded development, arrested growth, abnormal body coloration, and other symptoms, suggesting that the bacterium is essential for normal development and growth of the host insect. PMID- 11772650 TI - Transmission of Escherichia coli O157:H7 from contaminated manure and irrigation water to lettuce plant tissue and its subsequent internalization. AB - The transmission of Escherichia coli O157:H7 from manure-contaminated soil and irrigation water to lettuce plants was demonstrated using laser scanning confocal microscopy, epifluorescence microscopy, and recovery of viable cells from the inner tissues of plants. E. coli O157:H7 migrated to internal locations in plant tissue and was thus protected from the action of sanitizing agents by virtue of its inaccessibility. Experiments demonstrate that E. coli O157:H7 can enter the lettuce plant through the root system and migrate throughout the edible portion of the plant. PMID- 11772651 TI - Dissolved organic nitrogen hydrolysis rates in axenic cultures of Aureococcus anophagefferens (Pelagophyceae): comparison with heterotrophic bacteria. AB - The marine autotroph Aureococcus anophagefferens (Pelagophyceae) was rendered axenic in order to investigate hydrolysis rates of peptides, chitobiose, acetamide, and urea as indicators of the ability to support growth on dissolved organic nitrogen. Specific rates of hydrolysis varied between 8 and 700% of rates observed in associated heterotrophic marine bacteria. PMID- 11772652 TI - Electrochemical regeneration of Fe(III) to support growth on anaerobic iron respiration. AB - Here we describe artificial help for the respiratory electron flow supporting anaerobic growth of Thiobacillus ferrooxidans through exogenous electrolysis. Flux between H(2) and a anode through cells was accomplished with electrochemical regeneration of iron. The electrochemical help resulted in a 12-fold increase in yield compared with the yield observed in its absence. PMID- 11772653 TI - Cloning and characterization of the crystal protein-encoding gene of Bacillus thuringiensis subsp. yunnanensis. AB - Molecular cloning and characterization of a novel cry gene, cry32Aa, of Bacillus thuringiensis subsp. yunnanensis was carried out. The Cry32Aa protein was predicted to have a molecular mass of 139.2 kDa and was found to have an unusual 42-amino-acid-long tail at the C terminus. The cry32Aa gene was localized on the 103-MDa plasmid of the organism. Bioassays showed no toxicity against several moths and mosquitoes. However, it exhibited weak toxicity against larvae of the diamondback moth, Plutella xylostella. PMID- 11772654 TI - Monitoring of Ralstonia eutropha KT1 in groundwater in an experimental bioaugmentation field by in situ PCR. AB - Ralstonia eutropha KT1, which degrades trichloroethylene, was injected into the aquifer after activation with toluene, and then the number of bacteria was monitored by in situ PCR targeting the phenol hydroxylase gene and by fluorescent in situ hybridization (FISH) targeting 16S rRNA. Before injection of the bacterial suspension, the total concentration of bacteria in the groundwater was approximately 3 x 10(5) cells/ml and the amount of Ralstonia and bacteria carrying the phenol hydroxylase gene as a percentage of total bacterial cells was less than 0.1%. The concentration of bacteria carrying the phenol hydroxylase gene detected by in situ PCR was approximately 3 x 10(7) cells/ml 1 h after injection, and the concentration of Ralstonia detected by FISH was similar. The number of bacteria detected by in situ PCR was similar to that detected by FISH 4 days after the start of the extraction of groundwater. On and after day 7, however, the number of bacterial cells detected by FISH was less than that detected by in situ PCR. PMID- 11772655 TI - Isolation of Gemmata-like and Isosphaera-like planctomycete bacteria from soil and freshwater. AB - New cultured strains of the planctomycete division (order Planctomycetales) of the domain Bacteria related to species in the genera Gemmata and Isosphaera were isolated from soil, freshwater, and a laboratory ampicillin solution. Phylogenetic analysis of the 16S rRNA gene from eight representative isolates showed that all the isolates were members of the planctomycete division. Six isolates clustered with Gemmata obscuriglobus and related strains, while two isolates clustered with Isosphaera pallida. A double-membrane-bounded nucleoid was observed in Gemmata-related isolates but not in Isosphaera-related isolates, consistent with the ultrastructures of existing species of each genus. Two isolates from this study represent the first planctomycetes successfully cultivated from soil. PMID- 11772656 TI - Characterization of a Sinorhizobium isolate and its extracellular polymer implicated in pollutant transport in soil. AB - A bacterium isolated from soil (designated 9702-M4) synthesizes an extracellular polymer that facilitates the transport of such hydrophobic pollutants as polynuclear aromatic hydrocarbons, as well as the toxic metals lead and cadmium in soil. Biolog analysis, growth rate determinations, and percent G+C content identify 9702-M4 as a strain of Sinorhizobium meliloti. Sequence analysis of a 16S rDNA fragment gives 9702-M4 a phylogenetic designation most closely related to Sinorhizobium fredii. The extracellular polymer of isolate 9702-M4 is composed of both an extracellular polysaccharide (EPS) and a rough lipopolysaccharide. The EPS component is composed mainly of 4-glucose linkages with monomers of galactose, mannose, and glucuronic acid and has pyruval and acetyl constituents. The lipid fraction and the negative charge associated with carbonyl groups of the exopolymer are thought to account for the binding of polynuclear aromatic hydrocarbons and cationic metals. PMID- 11772657 TI - Cryptosporidium parvum mixed genotypes detected by PCR-restriction fragment length polymorphism analysis. AB - Combinations of 10 Cryptosporidium parvum oocysts, with various ratios of genotype I to genotype II, were isolated and subjected to PCR-restriction fragment length polymorphism analysis. Amplification of both genotypes in these samples ranged from 31 to 74% and yielded no information about the genotype proportions. In addition, since both genotypes were not always detected, amplification of a single genotype is not conclusive evidence that the sample contains only a single genotype. PMID- 11772658 TI - Hyperthermostable endoglucanase from Pyrococcus horikoshii. AB - An endoglucanase homolog from the hyperthermophilic archaeon Pyrococcus horikoshii was expressed in Escherichia coli, and its enzymatic characteristics were examined. The expressed protein was a hyperthermostable endoglucanase which hydrolyzes celluloses, including Avicel and carboxymethyl cellulose, as well as beta-glucose oligomers. This enzyme is the first endoglucanase belonging to glycosidase family 5 found from Pyrococcus species and is also the first hyperthermostable endoglucanase to which celluloses are the best substrates. This enzyme is expected to be useful for industrial hydrolysis of cellulose at high temperatures, particularly in biopolishing of cotton products. PMID- 11772659 TI - The microbial community structure of drinking water biofilms can be affected by phosphorus availability. AB - Microbial communities in biofilms grown for 4 and 11 weeks under the flow of drinking water supplemented with 0, 1, 2, and 5 microg of phosphorus liter(-1) and in drinking and warm waters were compared by using phospholipid fatty acids (PLFAs) and lipopolysaccharide 3-hydroxy fatty acids (LPS 3-OH-FAs). Phosphate increased the proportion of PLFAs 16:1 omega 7c and 18:1 omega 7c and affected LPS 3-OH-FAs after 11 weeks of growth, indicating an increase in gram-negative bacteria and changes in their community structure. Differences in community structures between biofilms and drinking and warm waters can be assumed from PLFAs and LPS 3-OH-FAs, concomitantly with adaptive changes in fatty acid chain length, cyclization, and unsaturation. PMID- 11772660 TI - Natural genetic transformation of clinical isolates of Escherichia coli in urine and water. AB - Transfer of plasmid-borne antibiotic resistance genes in Escherichia coli wild type strains is possible by transformation under naturally occurring conditions in oligotrophic, aquatic environments containing physiologic concentrations of calcium. In contrast, transformation is suppressed in nitrogen-rich body fluids like urine, a common habitat of uropathogenic strains. Current knowledge indicates that transformation of these E. coli wild-type strains is of no relevance for the acquisition of resistance in this clinically important environment. PMID- 11772661 TI - Transcriptional regulation of Nostoc hydrogenases: effects of oxygen, hydrogen, and nickel. AB - The transcription of structural genes encoding two hydrogenases in N(2)-fixing cultures of the cyanobacteria Nostoc muscorum and Nostoc sp. strain PCC 73102 were examined by reverse transcription-PCR. A low level of oxygen and addition of nickel induce higher transcript levels of both hydrogenases, whereas molecular hydrogen has a positive effect on the transcription of the genes encoding only the uptake hydrogenase. PMID- 11772662 TI - Hyperbaric oxygen does not prevent neurologic sequelae after carbon monoxide poisoning. AB - Delayed neurologic sequelae occur in up to 40% of severe carbon monoxide (CO) poisonings. Conflicting clinical data support the efficacy of hyperbaric oxygen (HBO) therapy in the acute treatment of CO poisoning. OBJECTIVE: To determine whether oxygen therapy reduces neurologic sequelae after CO poisoning in mice. METHODS: Male Swiss-Webster mice were exposed to CO at 1,000 ppm for 40 minutes and then 50,000 ppm until loss of consciousness (LOC) (4-9 additional minutes). Total time of both phases of CO exposure was 40-49 minutes. Treatment included HBO with 3 atmospheres (ATA) 100% oxygen, normobaric oxygen (NBO) with 1 ATA 100% oxygen, or ambient air 15 minutes after LOC. All animals underwent passive avoidance training and memory was assessed by measuring step-down latency (SDL) and step-up latency (SUL) seven days following CO exposure. RESULTS: Carbon monoxide poisoning induced significant memory deficits (SDL(CO) = 156 sec; SUL(CO) = 75%) compared with nonpoisoned (NP) animals (SDL(NP) = 272 sec; SUL(NP) = 100%). Both HBO and NBO did not prevent these neurologic sequelae. Furthermore, no significant neurobehavioral differences were found between HBO and NBO. Histologic examination of the CA1 layer of the hippocampus for pyknotic cells showed significant damage from CO in the air-treated animals (9.6%) but not in the nonpoisoned animals (3.8%). No significant neuroprotection was seen histologically with NBO and HBO compared with ambient air. CONCLUSIONS: These results suggest that HBO is not effective in preventing neurologic sequelae in mice and that there is no benefit of HBO over NBO following severe CO neurotoxicity. PMID- 11772663 TI - A randomized clinical trial of oral versus intramuscular delivery of steroids in acute exudative pharyngitis. AB - Previous study has shown that the use of intramuscular (IM) steroid leads to improved symptoms in patients with group A beta-hemolytic streptococcus (GABHS). OBJECTIVE: To compare oral with IM steroids as an adjunct to antibiotic therapy in the treatment of acute exudative pharyngitis. The null hypothesis was that there would be no difference in effectiveness of oral versus IM steroids. METHODS: The study was a randomized, double-blind outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin or, if allergic to penicillin, a ten-day course of polyenteric-coated erythromycin. Each patient was randomized to receive either injectable steroid plus oral placebo or injectable placebo plus oral steroid. All medications were given in the emergency department. All patients were contacted by telephone at 24 hours (first follow-up) and 48 hours (second follow-up) by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily for the third to seventh day after the initial visit. The time to total resolution of the sore throat was documented. The main outcome measures were time to complete relief of pain and VAS scores. Pain medication was not controlled; however, use of pain medications and amounts were recorded. RESULTS: A total of 78 patients were initially enrolled in the study. Eight patients were excluded from the statistical analysis because of inability to follow up. A total of 70 were entered, with 35 randomized to IM steroid plus oral placebo and 35 to IM placebo plus oral steroid. There was no difference in pain scores for the oral versus IM group at first follow-up (p = 0.13) and second follow-up (p = 0.82), and in number of hours to relief of pain (p = 0.06). Using repeated-measures analysis of variance, no difference in the effects of the two medications over time was detected (p = 0.83). CONCLUSIONS: The results of this clinical trial suggest that oral steroid and IM steroid provide similar levels of pain relief in acute exudative pharyngitis. PMID- 11772664 TI - Satisfied Patients Exiting the Emergency Department (SPEED) Study. AB - BACKGROUND/OBJECTIVE: Patient satisfaction has been associated with patient perceptions of emergency department (ED) wait intervals, but not necessarily actual wait intervals. The objective was to address the associations of actual versus perceived wait intervals in ED patients and the association of overall satisfaction with perceived and actual wait intervals. METHODS: The authors performed a prospective, cross-sectional study using a volume-stratified sample of adult ED patients presenting to an urban, university teaching hospital. Patient wait intervals were monitored using a computerized tracking system. Patients were confidentially surveyed regarding their overall satisfaction with care and perceptions of wait intervals after a disposition decision was made by the treating physician. The Spearman's rho (two-tailed, alpha = 0.05) was used to evaluate the association between patient satisfaction and perceived wait intervals, estimated wait intervals, and measured wait intervals. Associations between these measures of wait intervals were similarly assessed. RESULTS: One hundred twenty-six eligible patients (including 15 admissions) completed the survey. The median wait interval (interquartile range [IQR] was 14 (7 to 22) minutes to a room. Overall satisfaction was more strongly associated with the perception that the wait interval to a room was shorter than expected (r = 0.44; p = 0.00001) than with the estimated wait interval (r = 0.03; p = 0.97) or the measured wait interval (r = -0.06; p = 0.49). Patients had a median wait interval of 13 (3 to 26) minutes in a room until seen by a physician. Overall satisfaction was more strongly associated with the perception of the physician wait interval's being shorter than expected (r = 0.37; p = 0.00001) than with the estimated wait interval (r = -0.09; p = 0.32) or the measured wait interval (r = 0.05; p = 0.58). Similar findings were found for the total time in the ED. For both the wait for a room interval and the wait for a physician interval, the measured wait intervals were more strongly associated with the estimated wait intervals (r = 0.63 and r = 0.34, respectively) than with the perception that the wait intervals were shorter than expected (r = -0.20 and r = -0.17, respectively). CONCLUSIONS: Efforts to improve ED patient satisfaction should focus on improving patients' perceptions that wait intervals are appropriate rather than simply shortening wait intervals per se. PMID- 11772665 TI - Parental use and misuse of antibiotics: are there differences in urban vs. suburban settings? AB - OBJECTIVE: To compare the frequencies with which suburban and urban parents give their children antibiotics without first consulting a physician. METHODS: This was a prospective, comparative survey of a suburban emergency department (ED) patient population in New Jersey with an annual patient census of 60,000 visits and an urban ED in Connecticut with 58,000 annual visits. A convenience sample of parents with children <18 years of age were enrolled. Patients who were critically ill and/or not oriented were excluded. Subjects provided written answers to a series of closed questions regarding their knowledge and use of antibiotics for their children over the previous 12 months. Categorical data were analyzed by chi-square and Fisher's exact test; continuous data were analyzed by t-tests. All tests were two-tailed with alpha set at 0.05. The primary endpoint, antibiotic "misuse," was defined as parental administration of antibiotics to a child during the previous 12 months without the consultation of a physician. RESULTS: Eight hundred one parents were enrolled; 424 at the suburban site. Parents in the suburban site were significantly different with regard to mean age (39 +/- 7.2 vs. 32 +/- 9.0, p < 0.001), percentage female sex (63% vs. 81%, p < 0.001), percentage white race (78% vs. 34%, p < 0.001), and percentage with private insurance (89% vs. 56%, p < 0.001). A higher percentage of parents at the suburban site had misused antibiotics (12.1% vs. 4.0%; p < 0.001). Using logistic regression, this significant difference in the rate of antibiotic misuse between the two groups remained after adjustment for demographic variables and insurance status of the parents (p < 0.001). Parents at the suburban site were significantly less likely to have been previously discharged with their child from an office or ED setting without antibiotics only to go soon afterwards to another health facility in order to obtain such medications (5% vs. 48%; p < 0.001). CONCLUSIONS: Parents in the suburban setting were more likely to have misused antibiotics for their children. On the other hand, parents in the urban setting were more likely to have been discharged by a physician at one health facility and gone to another physician's office or ED in order to obtain antibiotics for their children. PMID- 11772666 TI - Urine dipstick as a screening test for serum creatinine elevation in emergency department patients with severe hypertension. AB - OBJECTIVE: Patients presenting to the emergency department (ED) with severe hypertension require assessment for acute end-organ damage. Serum creatinine (SCr) measurement is routinely recommended to detect renal dysfunction. The authors assessed the utility of the urine dipstick test in screening for acute SCr elevation in this population. METHODS: The authors performed a prospective study of adult ED patients with diastolic blood pressures > or = 115 mm Hg that persisted for > or = 30 minutes or necessitated emergent treatment. Excluded were menstruating and pregnant women and patients with urinary infection, trauma, or dialysis dependence. Patients reporting a history of renal disease were excluded if the SCr was abnormal and no baseline value was available. Each subject had an SCr and urine dipstick test. The authors examined the performance of the dipstick in identifying an elevated SCr, defined as SCr > 1.2 mg/dL or > 25% above baseline. RESULTS: Of 143 patients, 42 had SCr > 1.2 mg/dL. Eighteen reported prior renal disease but had an SCr that was normal or < or = 25% above baseline. The remaining 24 subjects comprised the elevated SCr group. The presence of either proteinuria or hematuria on dipstick identified these patients with 100% sensitivity and 29.7% specificity. Specificity rose to 42.4% without loss of sensitivity when an abnormal dipstick was defined as hematuria or > or = 1+ proteinuria. CONCLUSIONS: The urine dipstick may be an effective screening test for SCr elevation in patients with severe hypertension. A restrictive definition of an abnormal dipstick would identify all patients with elevated SCr and substantially reduce the number of SCr assays necessary. PMID- 11772667 TI - Pulmonary aspiration risk during emergency department procedural sedation--an examination of the role of fasting and sedation depth. AB - The assessment of pre-procedure fasting and control of sedation depth are prominent elements of widely disseminated procedural sedation guidelines and of the Joint Commission on Accreditation of Healthcare Organizations' standards. Both exist primarily to minimize the risk of pulmonary aspiration of gastric contents. This paper critically examines the literature on pre-procedure fasting and controlling sedation depth in association with pulmonary aspiration, and interprets this evidence in the context of modern emergency medicine practice. The article reviews the pathophysiology of aspiration and changing concepts regarding aspiration risk over the last decade. After reviewing studies on aspiration risk during general anesthesia, the paper reviews the risk of aspiration during labor and delivery as a more appropriate comparison group for aspiration risk during emergency department procedural sedation and analgesia (ED PSA). It is noted that aspiration during ED PSA has not been reported in the medical literature and that aspiration during general anesthesia and labor and delivery is uncommon. The literature provides no compelling evidence to support specific fasting periods for either liquids or solids prior to PSA, and existing guidelines for elective patients are of necessity arbitrary and based upon consensus opinion. The article discusses the implications in the areas of training and preparedness, monitoring, and research for the emergency physician practicing PSA. PMID- 11772668 TI - Selective tomographic imaging of patients with new-onset seizure disorders. AB - OBJECTIVE: Significant benefit could be realized by developing a clinical decision rule for new-onset seizure victims that would be capable of discriminating between patients having relevant structural lesions visible on computed tomographic (CT) imaging and those who do not. This study sought to determine whether a reliable decision rule could be developed using a limited number of clinical and demographic characteristics. METHODS: Chi-squared recursive partitioning was applied in a secondary analysis of the EMERGEncy ID NET database of new-onset seizure victims. Variables in this database (age, sex, race, ethnicity, seizure type, history of HIV or cysticercosis, and presence or absence of lateralizing neurologic findings or altered mentation) provided the partitioning variables, while CT imaging results provided outcome measures. The study sought to develop a decision rule with 100% sensitivity for detecting any intracranial lesions, and a separate rule with 100% sensitivity for detecting lesions of emergent concern. RESULTS: A decision rule using age > or = 65 years, lateralizing neurologic findings, altered mentation, high risk or known HIV infection, history of cysticercosis, and Hispanic ethnicity showed a sensitivity of 91.9% [95% confidence interval (95% CI) = 88.8% to 94.9%] in detecting individuals who had any tomographic finding. This rule had a sensitivity of 90.1% (95% CI = 83.4% to 96.7%) in detecting individuals with emergent tomographic findings. CONCLUSIONS: Recursive partitioning failed to produce a decision rule capable of reliably identifying new-onset seizure patients who have important lesions identified on CT. Future attempts to formulate such an instrument may need to include additional variables. In the interim, physicians should use liberal tomographic imaging in evaluating patients who present with new-onset seizures. PMID- 11772669 TI - Tissue harmonic imaging improves organ visualization in trauma ultrasound when compared with standard ultrasound mode. AB - The focused abdominal sonography for trauma (FAST) examination is complicated by brightly lit trauma bays, limited time, and body habitus. Recently, new ultrasound (US) technology has become available that improves organ visualization in abdominal scans. OBJECTIVE: The hypothesis was that a new US mode, tissue harmonic (TH) imaging, improves visualization of critical organ relationships in the FAST examination by making use of previously unused frequencies. The authors performed a blind, prospective observational study to compare the images obtained in typical FAST views with those obtained in standard US and TH modes. METHODS: Blunt trauma patients presenting to a level I trauma center between April and September 2000 were enrolled on a convenience basis. Typical FAST views were obtained in standard and TH modes. The emergency ultrasonographer (EU) switched between modes for each view, optimizing the gain each time. Multiple digital still images were made with all indications of the mode used disguised. For each view on a patient, the best image in each mode was selected in a blinded fashion. Three experienced EUs, blinded to the mode used, rated each image pair for resolution, detail, and total image quality as previously defined on a ten-point Likert scale, 10 being the best for each category. Wilcoxon signed-ranks test, 95% confidence intervals (95% CIs), and interobserver correlation were calculated. RESULTS: A total of 76 image groups (39 of Morison's pouch, 20 splenorenal, and 17 bladder) from 52 patients were rated. Tissue harmonics produced improved resolution, detail, and quality when compared with the standard US mode, with median scores of 6.7 vs. 6.0, 6.7 vs. 6.0, and 6.3 vs. 6.0, respectively. The differences of 0.7 (95% CI = 0.4 to 0.93), 0.7 (95% CI = 0.4 to 0.93), and 0.33 (95% CI = 0.17 to 0.67) were statistically significant, with p = 0.0001, 0.0001, and 0.0003, respectively. There was good interobserver agreement (kappa = 0.74; 95% CI = 0.68 to 0.79). CONCLUSIONS: Tissue harmonics produced FAST images higher in detail, resolution, and total image quality than standard mode US images. PMID- 11772671 TI - Child pedestrian injury in an urban setting: descriptive epidemiology. AB - OBJECTIVE: To describe the epidemiology of pedestrian injuries to children and adolescents (ages <20 years) in an urban setting, providing analyses of environmental and pedestrian variables. METHODS: Anonymous data were obtained for all motor vehicle crashes occurring in New York City over a seven-year period (1991-1997). RESULTS: Among 693,283 crashes, 97,245 resulted in injuries to 100,261 pedestrians, of whom 32,578 were under the age of 20. Using census counts for the denominator, the overall incidence of pediatric pedestrian injuries was 246/100,000 per year, and the case fatality rate was 0.6%. Incidence rates peaked in the 6-14-year age group, and showed a modest annual decline during the study period. Younger children were more likely to be struck mid-block and during daylight hours, whereas adolescents were more likely to be struck at intersections and at night. For younger children, there was a sharp peak in incidence during the summer months. Road and weather conditions did not appear to affect injury risk. CONCLUSIONS: These results help identify priorities for child pedestrian injury prevention and education, inform public health policy, and direct emergency medical health services resource allocation. PMID- 11772672 TI - Complications of ultrarapid opioid detoxification with subcutaneous naltrexone pellets. AB - Rapid and ultrarapid opioid detoxification (ROD and UROD) centers promise quick, painless, same-day detoxification treatment for patients with opioid addiction. The goal of ROD and UROD is to provide a rapid transition from opioid dependency to oral naltrexone therapy. The patient is given general anesthesia and high-dose opioid antagonists. This induces a severe withdrawal but spares the patient the experience. In theory, the process is complete within four to five hours. The patient awakens without opioid dependency and is started on oral naltrexone. Any subsequent, persistent withdrawal symptoms are treated symptomatically. A novel, unapproved approach is to compound a pellet of naltrexone and implant it in the subcutaneous tissue. In theory, this should result in continuous therapeutic levels for this drug, and avoid issues with noncompliance. CASE SERIES: This article reports six cases of complications from the same detoxification center that performed UROD with naltrexone pellet implantation, including pulmonary edema, prolonged withdrawal, drug toxicity, withdrawal from cross-addiction to alcohol and benzodiazepines, variceal rupture, aspiration pneumonia, and death. CONCLUSIONS: The risks of this procedure are great and further studies should assess its safety and the novel use of naltrexone. PMID- 11772673 TI - Emergency contraception provision: a survey of emergency department practitioners. AB - OBJECTIVES: To determine emergency department (ED) practitioner willingness to offer emergency contraception (EC) following sexual assault and consensual sex, and to compare responses of practitioners from states whose laws permit the refusal, discussion, counseling, and referral of patients for abortions (often called "opt-out" or "abortion-related conscience clauses") with those of practitioners from states without these laws. METHODS: Using a structured questionnaire, a convenience sample of ED practitioners attending a national emergency medicine meeting was surveyed. RESULTS: The 600 respondents were: 71% male, 29% female; 34% academic, 26% community, and 33% resident physicians; and 7% nurse practitioners and physician assistants. Many respondents (88%) were inclined to offer EC to those sexually assaulted by unknown assailants. More practitioners said they were willing to offer EC if the assailant was known to be HIV-infected rather than if the assailant had low HIV risk factors (90% vs. 79%, p < 0.01). More respondents would prescribe EC after sexual assault than consensual sex (88% vs. 73%, p < 0.01). The rates of willingness to offer EC were the same for practitioners in states with "abortion-related conscience clauses" and those from other states. CONCLUSIONS: Most ED practitioners said they were willing to offer EC. Although the risk of pregnancy exists after consensual sex, practitioners were less willing to prescribe EC after those exposures than for sexual assault. "Abortion-related conscience clauses" did not seem to influence willingness to offer EC. PMID- 11772674 TI - Carbon monoxide-induced deficits in cognitive performance of mice and lack of effect of hyperbaric oxygen treatment. PMID- 11772675 TI - Virtual reality and simulation: training the future emergency physician. AB - The traditional system of clinical education in emergency medicine relies on practicing diagnostic, therapeutic, and procedural skills on live patients. The ethical, financial, and practical weaknesses of this system are well recognized, but the alternatives that have been explored to date have shown even greater flaws. However, ongoing progress in the area of virtual reality and computer enhanced simulation is now providing educational applications that show tremendous promise in overcoming most of the deficiencies associated with live patient training. It will be important for academic emergency physicians to become more involved with this technology to ensure that our educational system benefits optimally. PMID- 11772676 TI - Emergency physician practices and requirements regarding the medical screening examination of psychiatric patients. AB - OBJECTIVE: To describe the testing requirements and practices of emergency physicians (EPs) when conducting a medical screening examination of psychiatric patients. METHODS: An anonymous survey was developed and mailed to 500 EPs randomly selected through American College of Emergency Physicians membership rolls. RESULTS: Two hundred ninety surveys were returned (58%). Eighty-five percent of the respondents were male, 70% practiced in a community setting and 28% in an academic setting, 58% were emergency medicine (EM) residency-trained, and 88% were EM board-certified or board-eligible. Ninety-eight percent stated they were actively involved with the psychiatric medical screening exam (PMSE). Routine testing was required by 35% of the respondents, with 16% being required by ED protocol, and 84% by the psychiatrist/psychiatric institute. Of those with required testing, tests required were: complete blood cell count (56%), electrolytes (56%), serum alcohol (85%), serum toxicology screen (31%), urine toxicology screen (86%), electrocardiogram (18%), liver function test (16%), blood urea nitrogen (45%), and creatinine (40%). Many clinicians believed that certain tests were unnecessary as part of a PMSE. There was no statistical difference between the opinions of the physicians required to test and those not required to test in terms of which tests they thought were a necessary part of a PMSE regardless of the patient's clinical presentation. The EM-trained physicians were also found to be significantly less likely to think certain tests were necessary for the PMSE when compared with the non-EM-trained physicians. CONCLUSIONS: Routine testing was required as part of the medical screening examination of psychiatric patients for only one-third of the respondents. Few respondents believed that any of these tests were necessary. Emergency medicine trained physicians were less likely to feel that routine testing was necessary. PMID- 11772677 TI - Integration of digital imaging into emergency medicine education. AB - Medical education has adopted the use of digital photography and other computer technology, which has changed the face of the classroom. Today's presentations couple a computer and digital projection system to create powerful teaching tools. Integration of quality medical images enhances presentations in a way never before possible and at a much lower cost. Changes to presentations can occur rapidly, at a fraction of the cost of slides. However, obtaining quality digital images for presentations is problematic. Services are available on the Internet that offer images for sale, but the cost to obtain images is high. Many institutions of higher learning provide images on the Internet for free, but the quality, number of available images, server capacity, and issues of consent limit the availability of these images. The authors describe their experience in collecting more than 20,000 clinical photographs, and provide examples of their use in emergency medicine education. PMID- 11772678 TI - Calculating the maintenance fluid rate. PMID- 11772679 TI - Extending indications for long-term pharmacotherapy: opportunities and challenges. PMID- 11772680 TI - Comorbidity of mood and anxiety disorders: the rule, not the exception? PMID- 11772681 TI - Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. AB - OBJECTIVE: Although four meta-analytic reviews support the efficacy of pharmacotherapy and behavior therapy for the treatment of insomnia, no meta analysis has evaluated whether these treatment modalities yield comparable outcomes during acute treatment. The authors conducted a quantitative review of the literature on the outcome of the two treatments to compare the short-term efficacy of pharmacotherapy and behavioral therapy in primary insomnia. METHOD: They identified studies from 1966 through 2000 using MEDLINE, psycINFO, and bibliographies. Investigations were limited to studies using prospective measures and within-subject designs to assess the efficacy of benzodiazepines or benzodiazepine receptor agonists or behavioral treatments for primary insomnia. Benzodiazepine receptor agonists included zolpidem, zopiclone, and zaleplon. Behavioral treatments included stimulus control and sleep restriction therapies. Twenty-one studies summarizing outcomes for 470 subjects met inclusion criteria. RESULTS: Weighted effect sizes for subjective measures of sleep latency, number of awakenings, wake time after sleep onset, total sleep time, and sleep quality before and after treatment were moderate to large. There were no differences in magnitude between pharmacological and behavioral treatments in any measures except latency to sleep onset. Behavior therapy resulted in a greater reduction in sleep latency than pharmacotherapy. CONCLUSIONS: Overall, behavior therapy and pharmacotherapy produce similar short-term treatment outcomes in primary insomnia. PMID- 11772682 TI - The human genome: mutations. PMID- 11772683 TI - Treating a child with Asperger's disorder and comorbid bipolar disorder. PMID- 11772684 TI - The Lexington narcotic farm. PMID- 11772685 TI - Catechol o-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder. AB - OBJECTIVE: Genetic epidemiologic and clinical data suggest that comorbid panic disorder may define a subtype of bipolar disorder. Comorbid panic disorder might thereby influence the strength of association between bipolar disorder and genes that have been implicated in bipolar disorder on the basis of their function in monoamine neurotransmission and previously reported linkage results. Polymorphic markers at catechol O-methyltransferase (COMT), serotonin transporter (5-HTT), and tryptophan hydroxylase (TPH) genes were analyzed in a case-control association study of bipolar disorder patients with or without lifetime panic disorder. METHOD: Unrelated subjects of Italian descent meeting DSM-III-R criteria for lifetime bipolar disorder (N=111), with (N=49) or without (N=62) comorbid lifetime panic disorder, were compared to 127 healthy subjects. DNA was extracted from blood leukocytes. The frequencies of COMT Val158Met, 5-HTTLPR, and TPH IVS7+218C>A polymorphisms were determined. Genotype and allele frequency comparisons between affected (bipolar disorder, bipolar disorder without panic disorder, or bipolar disorder with panic disorder) and unaffected individuals were carried out with chi-square tests or Fisher's exact tests. RESULTS: Relative to the comparison subjects, subjects with bipolar disorder without panic disorder, but not those with comorbid bipolar disorder and panic disorder, showed significantly higher frequencies of the COMT Met158 and the short 5-HTTLPR alleles and genotypes. The differences in the frequencies of the TPH IVS7+218A alleles and genotypes approached statistical significance. CONCLUSIONS: The findings support the hypothesis that comorbid panic disorder identifies a genetic subtype of bipolar disorder and suggest a role for COMT and 5-HTT in vulnerability to these disorders. PMID- 11772686 TI - Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder. AB - OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes. PMID- 11772687 TI - Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic. AB - OBJECTIVE: The substantial discrepancy in the male-to-female ratio between clinic referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. METHOD: The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. RESULTS: Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. CONCLUSIONS: The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD. PMID- 11772688 TI - Gender, poverty, and postnatal depression: a study of mothers in Goa, India. AB - OBJECTIVE: This study described the natural history of depression in mothers who recently gave birth in a low-income country and to investigate the effect of risk factors, particularly related to infant gender bias, on the occurrence and outcome of depression. METHOD: The authors studied a group of pregnant mothers recruited during their third trimester of pregnancy from a district hospital in Goa, India. The mothers were interviewed at recruitment, 6-8 weeks, and 6 months after childbirth. Interview data included presence of antenatal and postnatal depression, obstetric history, economic and demographic characteristics, and gender-based variables (preference for male infant, presence of marital violence). RESULTS: Depressive disorder was detected in 59 (23%) of the mothers at 6-8 weeks after childbirth; 78% of these patients had had clinically substantial psychological morbidity during the antenatal period. More than one half of the patients remained ill at 6 months after delivery. Economic deprivation and poor marital relationships were important risk factors for the occurrence and chronicity of depression. The gender of the infant was a determinant of postnatal depression; it modified the effect of other risk factors, such as marital violence and hunger. Depressed mothers were more disabled and were more likely to use health services than nondepressed mothers. CONCLUSIONS: Maternal and infant health policies, a priority in low-income countries, must integrate maternal depression as a disorder of public health significance. Interventions should target mothers in the antenatal period and incorporate a strong gender-based component. PMID- 11772689 TI - Relationship of maternal smoking during pregnancy with criminal arrest and hospitalization for substance abuse in male and female adult offspring. AB - OBJECTIVE: Maternal prenatal smoking has been found to be related to externalizing behavior problems in male offspring, but this relationship has rarely been examined in female offspring. Preliminary evidence suggests that maternal prenatal smoking may be particularly related to antisocial behavior outcomes in male offspring and substance abuse problems in female offspring. This study attempted to replicate these findings in a large-scale, longitudinal community cohort study. METHOD: Subjects were a birth cohort of 4,169 male and 3,943 female offspring born between 1959 and 1961 in Copenhagen, Denmark. During the third trimester of pregnancy, the subjects' mothers self-reported the number of cigarettes smoked on a daily basis. When the offspring were adults, their criminal arrest histories and psychiatric hospitalizations for substance abuse were checked in national registers. Additional data were collected concerning maternal rejection of the infant, socioeconomic status, maternal age, pregnancy and delivery complications, use of drugs in pregnancy, paternal criminal history, and parental psychiatric hospitalization. RESULTS: Results indicate a dose response relationship between the amount of maternal prenatal smoking and both criminal arrest and psychiatric hospitalization for substance abuse in male and female offspring. These relationships remained significant after potential demographic, parental, and perinatal risk confounds were controlled. Hospitalization of offspring for substance abuse mediated the relationship between maternal prenatal smoking and criminal arrest for female but not for male offspring. CONCLUSIONS: Maternal prenatal smoking is related to criminal and substance abuse outcomes in male and female offspring. Higher rates of index arrests for female offspring may be related to their substance abuse problems. PMID- 11772690 TI - Gender differences in panic disorder: findings from the National Comorbidity Survey. AB - OBJECTIVE: Several epidemiological studies have demonstrated a higher prevalence of panic disorder in women than in men. This study explored whether the prevalence of specific panic symptoms differs by gender. METHOD: National Comorbidity Survey data from 609 respondents who met DSM-III-R criteria for panic disorder or panic attacks were analyzed to test for gender differences across 18 panic symptoms. RESULTS: Among National Comorbidity Survey respondents with panic disorder or panic attacks, female respondents were more likely than male respondents to experience respiration-related difficulties during panic attacks. CONCLUSIONS: Specific symptoms occurring during panic attacks differ by gender. The pathophysiology of these symptom differences may involve gender differences in sensitivity to CO(2) and in the threshold for panic attacks during hypoxic and hypercapnic states. PMID- 11772691 TI - Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. AB - OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered. PMID- 11772692 TI - [(3)H]cAMP binding sites and protein kinase a activity in the prefrontal cortex of suicide victims. AB - OBJECTIVE: The cAMP-dependent enzyme protein kinase A phosphorylates intracellular proteins upon activation and thereby plays a major role in mediating various physiological functions in the brain. To examine the role of this enzyme in suicidal behavior, the authors examined the catalytic and regulatory activities of protein kinase A in the postmortem brain of suicide victims. METHOD: Brain tissues were collected from 17 suicide victims and 17 nonpsychiatric comparison subjects. Regulatory activity was determined by examining [(3)H]cAMP binding to protein kinase A, while catalytic activity was determined by enzymatic assay in the presence (total activity) and the absence (endogenous activity) of cAMP in the membrane and cytosol fractions of the prefrontal cortex. RESULTS: The number (B(max)) of [(3)H]cAMP binding sites to protein kinase A was significantly lower in the suicide victims without any changes in affinity in either the membrane or cytosol fractions of the prefrontal cortex. Further, significantly less protein kinase A activity, both in the presence and the absence of cAMP, was seen in the membrane and cytosol fractions of the prefrontal cortex of suicide victims; however, the difference in total protein kinase A activity was much more pronounced. CONCLUSIONS: The results suggest that cAMP binding to the regulatory subunits of protein kinase A, as well as the phosphotransfer catalytic activity of protein kinase A, are lower in the prefrontal cortex of suicide victims than in nonpsychiatric comparison subjects, which may be of clinical relevance in the pathophysiology of suicidal behavior. PMID- 11772693 TI - Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease. AB - OBJECTIVE: In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests. METHOD: The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T(1)-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume. RESULTS: For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region. CONCLUSIONS: In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease. PMID- 11772694 TI - Clinicopathological validation study of four sets of clinical criteria for vascular dementia. AB - OBJECTIVE: The authors' goal was to validate the clinical criteria for vascular dementia of the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC), the National Institute for Neurological Disorders and Stroke Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), DSM-IV, and ICD-10. METHOD: Sensitivity and specificity were assessed by comparing the clinical with the neuropathological diagnosis of 89 autopsied patients with dementia from a geriatric and psychiatric hospital. All cases were reviewed by a clinician and a neuropathologist who were blind to each other's findings. RESULTS: Neuropathologically there were 20 cases of vascular dementia, 23 cases of mixed dementia, and 46 cases of Alzheimer's disease among the autopsied patients. The sensitivity was 0.50 for DSM-IV criteria for vascular dementia, 0.70 for ADDTC criteria for possible vascular dementia, 0.55 for NINDS AIREN criteria for possible vascular dementia, 0.20 for ICD-10 criteria for vascular dementia, 0.25 for ADDTC criteria for probable vascular dementia, and 0.20 for NINDS-AIREN criteria for probable vascular dementia. Specificity was 0.84, 0.78, 0.84, 0.94, 0.91, and 0.93, respectively. The proportion of cases clinically classified as vascular dementia ranged from 0% to 13% for neuropathologically confirmed cases of Alzheimer's disease and 9% to 39% for neuropathologically confirmed cases of mixed dementia. There was no statistically significant relationship between the neuropathological diagnosis and three of the clinical criteria sets studied (ICD-10 criteria for vascular dementia and ADDTC and NINDS-AIREN criteria for probable vascular dementia). CONCLUSIONS: Clinical criteria for vascular dementia are not interchangeable. The ADDTC criteria for possible vascular dementia are the most sensitive for the detection of vascular dementia; however, the DSM-IV criteria for vascular dementia and the NINDS-AIREN criteria for possible vascular dementia may be more effective in excluding mixed dementia. Given their inability to detect the vast majority of cases of vascular dementia, the ICD-10 criteria for vascular dementia and the ADDTC and NINDS-AIREN criteria for probable vascular dementia should be revised. PMID- 11772695 TI - Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder. AB - OBJECTIVE: Obsessive-compulsive disorder (OCD) typically begins early in life and has a chronic course. Despite the need for long-term treatment, the authors found no placebo-controlled studies that have examined the relapse-prevention efficacy of maintenance therapy. METHOD: Patients who met criteria for response after 16 and 52 weeks of a single-blind trial of sertraline were randomly assigned to a 28 week double-blind trial of 50-200 mg/day of sertraline or placebo. Primary outcomes after the double-blind trial were full relapse, dropout due to relapse or insufficient response, or acute exacerbation of OCD symptoms. RESULTS: Of 649 patients at baseline, 232 completed 52 weeks of the single-blind trial and met response criteria. Among the 223 patients in the double-blind phase of the study, sertraline had significantly greater efficacy than placebo on two of three primary outcomes: dropout due to relapse or insufficient clinical response (9% versus 24%, respectively) and acute exacerbation of symptoms (12% versus 35%). Sertraline resulted in improvement in quality of life during the initial 52-week trial and continued improvement, significantly superior to placebo, during the subsequent 28-week double-blind trial. Long-term treatment with sertraline was well tolerated. Over the entire study period, less than 20% of the patients stopped treatment because of adverse events. CONCLUSIONS: Sertraline demonstrated sustained efficacy among patients responding to treatment and was generally well tolerated during the 80-week study. During the study's last 28 weeks, sertraline demonstrated greater efficacy than placebo in preventing dropout due to relapse or insufficient clinical response and acute exacerbation of OCD symptoms. PMID- 11772696 TI - A placebo-controlled study of fluoxetine in continued treatment of bulimia nervosa after successful acute fluoxetine treatment. AB - OBJECTIVE: The efficacy of fluoxetine in the acute management of bulimia nervosa is well established; however, few controlled studies have examined whether continuation of pharmacotherapy provides protection from relapse. This study compared the efficacy and safety of treatment with fluoxetine versus placebo in preventing relapse of bulimia nervosa during a 52-week period after successful acute fluoxetine therapy. METHOD: Patients who met DSM-IV criteria for bulimia nervosa, purging type, were assigned to single-blind treatment with 60 mg/day of fluoxetine. After 8 weeks of treatment, patients were considered responders if they experienced a decrease > or =50% from baseline in the frequency of vomiting episodes during 1 of the 2 preceding weeks. Responders were randomly assigned to receive 60 mg/day of fluoxetine or placebo and were monitored for relapse for up to 52 weeks. Patients met relapse criteria if they experienced a return to the baseline vomiting frequency that persisted for 2 consecutive weeks. RESULTS: Of the 232 patients who entered the acute phase, 150 patients (65%) met response criteria and were randomly assigned to receive fluoxetine (N=76) or placebo (N=74). Fluoxetine-treated patients exhibited a longer time to relapse than placebo-treated patients. Quantitative analysis of other efficacy measures, including frequency of vomiting episodes, frequency of binge eating episodes, Clinical Global Impression severity and improvement scores, the patient's global impression score, and Yale-Brown-Cornell Eating Disorder Scale score, indicated that the efficacy of fluoxetine treatment was statistically superior, compared to placebo. There were no clinically relevant differences in safety between groups. Attrition in this study was high, especially in the first 3 months after random assignment to treatment groups. CONCLUSIONS: Continued treatment with fluoxetine in patients with bulimia nervosa who responded to acute treatment with fluoxetine improved outcome and decreased the likelihood of relapse. PMID- 11772697 TI - Antipsychotic medication adherence: is there a difference between typical and atypical agents? AB - OBJECTIVE: Pharmacy refill records were used to compare medication adherence in outpatient veterans receiving typical versus atypical antipsychotic medications. METHOD: Consecutive patients meeting selection criteria and receiving prescriptions for haloperidol (N=57), perphenazine (N=60), risperidone (N=80), olanzapine (N=63), and quetiapine (N=28) over a 3-month period were identified from a computerized database. The hospital policy at the time of this study required failure in trials of at least two typical antipsychotics before initiation of an atypical agent. Patients' adherence with the antipsychotic regimen was calculated by analyzing refill records for up to 12 months. The cumulative mean gap ratio (the number of days when medication was unavailable in relation to the total number of days) and the compliant fill rate (the number of prescription fills indicating adherence in relation to the total number of prescription fills) at 6 and 12 months were calculated. RESULTS: Adherence rates at 6 and 12 months were moderately higher in patients who received atypical antipsychotics than in those who received typical agents. Cumulative mean gap ratios were 23.2% for typical and 14.1% for atypical antipsychotics at 12 months; thus, patients who received typical agents were without medication for an average of 7 days per month, compared with 4 days per month for those who received atypical agents. At 12 months, compliant fill rates were 50.1% for typical and 54.9% for atypical antipsychotics. CONCLUSIONS: Interventions to improve adherence are warranted even for patients who receive atypical antipsychotic medications. PMID- 11772698 TI - EEG abnormalities during treatment with typical and atypical antipsychotics. AB - OBJECTIVE: Clozapine produces EEG abnormalities and dose-dependent risk of epileptic seizures. Much less is known about EEG effects of newer antipsychotics. The present study therefore examined the risk of EEG abnormalities associated with various antipsychotic drugs. METHOD: EEG recordings from 323 hospitalized psychiatric patients (293 treated with antipsychotics, 30 who did not receive any antipsychotic treatment) were graded blind to diagnosis and treatment for type and severity of EEG abnormalities. Drug type, dose, and clinical factors were evaluated for association with EEG abnormalities by multivariate logistic regression. RESULTS: EEG abnormalities occurred in 56 subjects (19.1%) treated and four (13.3%) not treated with antipsychotics. EEG abnormality risk among antipsychotic agents varied greatly (clozapine=47.1%, olanzapine=38.5%, risperidone=28.0%, typical neuroleptics=14.5%, quetiapine=0.0%). Significant risk factors in order of influence were hypertension, use of an atypical antipsychotic, bipolar diagnosis, and older age; benzodiazepine cotreatment lowered risk. Unassociated with risk were sex, treatment response, length of hospital stay, drug potency, daily dose (in mg or mg/kg), drug exposure time, or cotreatments. CONCLUSIONS: EEG abnormality risk varied widely among specific antipsychotics. Risk was particularly high with clozapine and olanzapine, moderate with risperidone and typical neuroleptics, and low with quetiapine. Comorbid hypertension, bipolarity, and older age-but not dose or clinical response-were associated with risk. PMID- 11772699 TI - Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function. AB - OBJECTIVE: Because treatment of the depressed phase of bipolar disorder is a clinical challenge and hypothyroidism is known to be associated with depression, the authors examined the relationship between pretreatment thyroid values and response to antidepressant treatment. It was hypothesized that subjects with lower thyroid function, even within the normal range, would have a poorer response to initial treatment. METHOD: The subjects were 65 patients in the depressed phase of bipolar I disorder who were enrolled in a larger ongoing study. A panel of thyroid measures, including thyroid-stimulating hormone (TSH), thyroxine, triiodothyronine resin uptake, and free thyroxine index (FTI), were determined before initiation of algorithm-guided treatment. The effect of each thyroid measurement on time to remission was estimated by using the Cox proportional hazards model. RESULTS: Both lower values of FTI and higher values of TSH were significantly associated with longer times to remission, i.e., slower response to treatment. Outcomes were relatively poor unless patients had FTI values above the median and TSH values below the median. Patients with this optimal profile experienced remission 4 months faster than the remainder of the study group. CONCLUSIONS: This study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range. Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response. It remains to be seen whether pharmacological enhancement of thyroid function will facilitate recovery from bipolar depression. PMID- 11772700 TI - Changes in brain function of depressed subjects during treatment with placebo. AB - OBJECTIVE: It has been proposed that 50%-75% of the efficacy of antidepressant medication represents the placebo effect, since many depressed patients improve when treated with either medication or placebo. This study examined brain function in depressed subjects receiving either active medication or placebo and sought to determine whether quantitative electroencephalography (QEEG) could detect differences in brain function between medication and placebo responders. Both QEEG power and cordance, a new measure that reflects cerebral perfusion and is sensitive to the effect of antidepressant medication, were examined. METHOD: Fifty-one subjects with major depression were enrolled in one of two independent, 9-week double-blind, placebo-controlled studies in which either fluoxetine (N=24) or venlafaxine (N=27) was the active medication. Serial QEEG recordings were performed during the course of treatment. After 9 weeks, the blind was broken and subjects were classified as medication responders, placebo responders, medication nonresponders, or placebo nonresponders. RESULTS: No significant pretreatment differences in clinical or QEEG measures were found among the four outcome groups. Placebo responders, however, showed a significant increase in prefrontal cordance starting early in treatment that was not seen in medication responders (who showed decreased cordance) or in medication nonresponders or placebo nonresponders (who showed no significant change). There was no significant change in QEEG power during treatment. CONCLUSIONS: These findings suggest that "effective" placebo treatment induces changes in brain function that are distinct from those associated with antidepressant medication. If these results are confirmed, cordance may be useful for differentiating between medication and placebo responders. PMID- 11772701 TI - High choline concentrations in the caudate nucleus in antipsychotic-naive patients with schizophrenia. AB - OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) studies of medicated patients with schizophrenia suggest high choline levels in the caudate nucleus. However, assessments of antipsychotic-naive patients are needed. METHOD: The authors studied 11 antipsychotic-naive schizophrenia patients and 11 normal comparison subjects with single-voxel (1)H-MRS of the left caudate nucleus. Concentrations of N-acetylaspartate, choline, and creatine were determined and corrected for the proportion of cerebrospinal fluid in the voxel. RESULTS: The patients with schizophrenia had significantly higher levels of choline than the comparison subjects, while the other two metabolites did not differ between groups. CONCLUSIONS: High caudate choline levels in schizophrenia are not secondary to antipsychotic treatment. PMID- 11772702 TI - Elevation of prolactin levels by atypical antipsychotics. AB - OBJECTIVE: Atypical antipsychotics are thought not to elevate prolactin levels. The authors examined data suggesting that atypical antipsychotics do elevate prolactin levels but more transiently than typical antipsychotics. METHOD: Prolactin levels in 18 male patients with schizophrenia who were receiving atypical antipsychotics were monitored over the 24-hour period following administration of their daily oral dose of risperidone, olanzapine, or clozapine. RESULTS: The baseline prolactin levels in patients receiving risperidone (mean=27 ng/ml, SD=14) were abnormally high, but baseline prolactin levels in patients receiving olanzapine (mean=9 ng/ml, SD=5) and clozapine (mean=9 ng/ml, SD=5) were not high. All three atypical antipsychotics caused a doubling of prolactin levels over baseline levels 6 hours after medication administration. CONCLUSIONS: These data suggest that these atypical antipsychotics raise prolactin levels, although the increases with olanzapine did not reach statistical significance. This suggests that the differences in the effects on prolactin levels of atypical and typical antipsychotics are not categorical but lie in the degree and duration of dose-induced prolactin elevation, attributable to the differential binding properties of each drug on pituitary dopamine D(2) receptors. PMID- 11772703 TI - Use of atypical antipsychotics during pregnancy and the risk of neural tube defects in infants. AB - OBJECTIVE: Folate deficiency in early pregnancy and maternal adiposity, independent of folate intake, lead to a greater risk of neural tube defects in infants. Atypical antipsychotics cause various degrees of weight gain. The authors assessed folate status and obesity among patients with schizophrenia receiving atypical antipsychotics. METHOD: A sample of 70 inpatients and outpatients (21 of them women) who were taking antipsychotics was randomly selected. Body weight, body mass index, daily folate intake, and folate serum concentrations were determined. RESULTS: The majority of the patients were overweight. Only eight of 37 patients had folate intake above 400 microg/day, the level shown to be protective against neural tube defects. Mean serum folate was significantly lower than in a general hospital group of 810 patients. CONCLUSIONS: Women with schizophrenia who take atypical antipsychotics have a higher risk of neural tube defects in their infants because of the associated low intake of folate and obesity. PMID- 11772704 TI - Psychosis, psychopathy, and homicide: a preliminary neuropsychological inquiry. AB - OBJECTIVE: This study attempted to statistically distinguish subgroups of murderers with mental disorders from among 26 hospitalized men (mean age=34 years) who were committed to a maximum security forensic hospital. METHOD: Measures consisted of objective ratings of psychosis and psychopathy and neuropsychological tests of intelligence, memory and attention, executive functions, and academic abilities. RESULTS: Cluster analysis produced two distinct subgroups: one defined by high incidence of psychosis and low level of psychopathy and one by low incidence of psychosis and high level of psychopathy, each corresponding to distinct neuropsychological differences in intellectual abilities, learning disabilities, and social intelligence. CONCLUSIONS: In light of this relatively small, highly select group, these novel findings must be viewed as preliminary. Studies of larger cohorts are needed before definitive conclusions can be drawn as to the reliability of these two distinct symptom clusters, each independently validated by neuropsychological measures of intelligence, sociality, and academic abilities. PMID- 11772705 TI - Predictors of treatment utilization among women with anorexia and bulimia nervosa. AB - OBJECTIVE: The authors sought predictors of treatment utilization among women with eating disorders. METHOD: Women diagnosed with either anorexia or bulimia nervosa (N=246) completed prospective evaluations of eating disorder status, comorbid disorders, global assessment of functioning, and treatment utilization. RESULTS: Women with anorexia nervosa received significantly more inpatient treatment than did women with bulimia nervosa. Predictors of treatment utilization included lower global assessment of functioning scores and presence of personality disorders. CONCLUSIONS: Women with more severe pathology have higher treatment utilization rates. This pattern may explain the seeming lack of treatment efficacy for eating disorders outside of randomized controlled studies. PMID- 11772706 TI - Stress management and immune system reconstitution in symptomatic HIV-infected gay men over time: effects on transitional naive T cells (CD4(+)CD45RA(+)CD29(+)). AB - OBJECTIVE: Changes in immunologic status were evaluated in 25 HIV-infected men randomly assigned to a 10-week stress management intervention or a wait-list control condition. METHOD: The authors monitored changes in number of transitional naive T cells (CD4(+)CD45RA(+)CD29(+)) over 6-12 months after the completion of the intervention. RESULTS: Men receiving stress management had higher CD4(+) CD45RA(+)CD29(+) cell counts at follow-up than did the control subjects. This difference was independent of initial number of naive T cells and HIV virus load. CONCLUSIONS: Stress management is associated with immunologic reconstitution in HIV-positive gay men. PMID- 11772707 TI - GABA(A) receptor-modulating neuroactive steroid composition in patients with panic disorder before and during paroxetine treatment. AB - OBJECTIVE: Previous studies have shown that neuroactive steroids modulate anxiety and stress reactivity. However, no data on the possible role of these gamma aminobutyric acid(A) (GABA(A)) receptor-modulating neuroactive steroids in patients with anxiety disorders are available. METHOD: The concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-THP, 3beta,5alpha-THP, and their precursors were studied in the plasma of 10 patients with panic disorder and 10 matched healthy comparison subjects. In addition, the effects of paroxetine treatment on neuroactive steroid concentrations were studied in the panic disorder patients over a 24-week period. RESULTS: Unexpectedly, patients with panic disorder had significantly greater concentrations of the positive allosteric modulators 3alpha,5alpha-THP and 3alpha,5beta-THP and significantly lower concentrations of 3beta,5alpha-THP (a functional antagonist for GABA(A) agonistic steroids), which might result in greater GABA(A) receptor-mediated neuronal activity. Paroxetine treatment did not affect neuroactive steroid concentrations, which were highly stable over 24 weeks. CONCLUSIONS: Differences in neuroactive steroid composition in patients with panic disorder were the opposite of those seen in patients with major depression and may reflect counterregulative mechanisms against the occurrence of spontaneous panic attacks. PMID- 11772708 TI - MECP2 mutation in a boy with language disorder and schizophrenia. PMID- 11772709 TI - Levetiracetam for acute mania. PMID- 11772710 TI - Neuroleptic malignant syndrome and quetiapine. PMID- 11772711 TI - Increasing insulin dose for olanzapine-related diabetes. PMID- 11772712 TI - Postpartum panic disorder in a new father. PMID- 11772714 TI - Female psychiatrists. PMID- 11772716 TI - Discipline for psychiatrists. PMID- 11772717 TI - Treatment of psychosis at onset. PMID- 11772718 TI - Action of atypical antipsychotics. PMID- 11772719 TI - Action of atypical antipsychotics. PMID- 11772722 TI - Fluoxetine and olanzapine for resistant depression. PMID- 11772724 TI - Personality change after treatment. PMID- 11772726 TI - Abuse and ACTH response to corticotropin-releasing factor. PMID- 11772743 TI - Contribution of chronic conditions to aggregate changes in old-age functioning. PMID- 11772745 TI - Nonmedical exemptions to state immunization laws. PMID- 11772747 TI - September 11: the response and role of public health. PMID- 11772748 TI - A "health commons" approach to oral health for low-income populations in a rural state. AB - Oral health needs are urgent in rural states. Creative, broad-based, and collaborative solutions can alleviate these needs. "Health commons" sites are enhanced, community-based, primary care safety net practices that include medical, behavioral, social, public, and oral health services. Successful intervention requires a comprehensive approach, including attention to enhancing dental service capacity, broadening the scope of the dental skills of locally available providers, expanding the pool of dental providers, creating new interdisciplinary teams in enhanced community-based sites, and developing more comprehensive oral health policy. By incorporating oral health services into the health commons primary care model, access for uninsured and underserved populations is increased. A coalition of motivated stakeholders includes community leaders, safety net providers, legislators, insurers, and medical, dental, and public health providers. PMID- 11772749 TI - Attacks on science: the risks to evidence-based policy. AB - As government agencies, academic centers, and researchers affiliated with them provide an increasing share of the science base for policy decisions, they are also subject to efforts to politicize or silence objective scientific research. Such actions increasingly use sophisticated and complex strategies that put evidence-based policy making at risk. To assure the appropriate use of scientific evidence and the protection of the scientists who provide it, institutions and individuals must grow more vigilant against these tactics. Maintaining the capacity for evidence-based policy requires differentiating between honest scientific challenge and evident vested interest and responding accordingly, building and diversifying partnerships, assuring the transparency of funding sources, agreeing on rules for publication, and distinguishing the point where science ends and policy begins. PMID- 11772750 TI - Impact of targeted programs on health systems: a case study of the polio eradication initiative. AB - The results of 2 large field studies on the impact of the polio eradication initiative on health systems and 3 supplementary reports were presented at a December 1999 meeting convened by the World Health Organization. All of these studies concluded that positive synergies exist between polio eradication and health systems but that these synergies have not been vigorously exploited. The eradication of polio has probably improved health systems worldwide by broadening distribution of vitamin A supplements, improving cooperation among enterovirus laboratories, and facilitating linkages between health workers and their communities. The results of these studies also show that eliminating polio did not cause a diminution of funding for immunization against other illnesses. Relatively little is known about the opportunity costs of polio eradication. Improved planning in disease eradication initiatives can minimize disruptions in the delivery of other services. Future initiatives should include indicators and baseline data for monitoring effects on health systems development. PMID- 11772751 TI - On the front lines: an environmental asthma intervention in New York City. AB - Asthma is now the leading cause of school absence among children of color in impoverished urban neighborhoods. Environmental interventions have the potential to augment clinical approaches to asthma management by directly reducing exposure to environmental triggers (e.g., cockroaches, rodents, and mold). We implemented an apartment-based intervention to reduce exposures to indoor allergens among children living with asthma in 2 areas in New York City with rates of asthma morbidity and mortality that rank among the highest in the United States. Although the intervention phase of the present study is not yet complete, timely reporting of our field experiences may prove useful to other groups engaged in environmental intervention trials in urban communities. PMID- 11772752 TI - Beauty and the beast: results of the Rhode Island smokefree shop initiative. AB - Licensed hairdressing facilities are prevalent in communities nationwide and represent a unique and promising channel for delivering public health interventions. The Rhode Island Smokefree Shop Initiative tested the feasibility of using these facilities to deliver smoking policy interventions statewide. A statewide survey of hairdressing facilities was followed by interventions targeted to the readiness level (high/low) of respondents to adopt smoke-free policies. PMID- 11772753 TI - The World Health Report 2000: can health care systems be compared using a single measure of performance? PMID- 11772754 TI - The World Health Report 2000: can health care systems be compared using a single measure of performance? PMID- 11772755 TI - The tooth puller [L'arracheur de dents]. PMID- 11772756 TI - Public careers and private sexuality: some gay and lesbian lives in the history of medicine and public health. AB - This study explores the careers of 5 physicians active in public health and medicine during the first half of the 20th century to illustrate interactions between private and professional life. An examination of these individuals, who might today be variously designated as gay, lesbian, bisexual, transgender, or queer, suggests how historical understanding can be enriched by a greater willingness to investigate intimacy and sexual life as potentially relevant to career and achievements. Further, the narratives support a plea for all historians to provide readers with a more frank acknowledgment of the possible relevance of personal life to intellectual work, even in the sciences. Additionally, this historical exploration of ways that careers and achievements may have been affected by a person's homosexuality (even when the person did not publicly embrace a gay identity) opens up a new area of research through biographical sketches based on historical sources combined with generalizations that are intentionally provisional. Included are the stories of Sara Josephine Baker, Harry Stack Sullivan, Ethel Collins Dunham, Martha May Eliot, and Alan L. Hart. PMID- 11772757 TI - School-based screening for asthma in third-grade urban children: the Passaic asthma reduction effort survey. PMID- 11772758 TI - Severely reduced functional status in veterans fitting a case definition of Gulf War syndrome. PMID- 11772759 TI - Wheelchair users at home: few home modifications and many injurious falls. PMID- 11772760 TI - Lack of oral health care for adults in Harlem: a hidden crisis. AB - OBJECTIVES: Profound and growing disparities exist in oral health among certain US populations. We sought here to determine the prevalence of oral health complaints among Harlem adults by measures of social class, as well as their access to oral health care. METHODS: A population-based survey of adults in Central Harlem was conducted from 1992 to 1994. Two questions on oral health were included: whether participants had experienced problems with their teeth or gums during the past 12 months and, if so, whether they had seen a dentist. RESULTS: Of 50 health conditions queried about, problems with teeth or gums were the chief complaint among participants (30%). Those more likely to report oral health problems than other participants had annual household incomes of less than $9000 (36%), were unemployed (34%), and lacked health insurance (34%). The privately insured were almost twice as likely to have seen a dentist for oral health problems (87%) than were the uninsured (48%). CONCLUSIONS: There is an urgent need to provide oral health services for adults in Harlem. Integrating oral health into comprehensive primary care is one promising mechanism. PMID- 11772761 TI - Problems with access to dental care for Medicaid-insured children: what caregivers think. AB - OBJECTIVES: This study aimed to gain insight into the experiences, attitudes, and perceptions of a racially and ethnically diverse group of caregivers regarding barriers to dental care for their Medicaid-insured children. METHODS: Criterion purposive sampling was used to select participants for 11 focus groups, which were conducted in North Carolina. Seventy-seven caregivers of diverse ethnic and racial backgrounds participated. Full recordings of sessions were obtained and transcribed. A comprehensive content review of all data, including line-by-line analysis, was conducted. RESULTS: Negative experiences with the dental care system discouraged many caregivers in the focus groups from obtaining dental services for their Medicaid-insured children. Searching for providers, arranging an appointment where choices were severely limited, and finding transportation left caregivers describing themselves as discouraged and exhausted. Caregivers who successfully negotiated these barriers felt that they encountered additional barriers in the dental care setting, including long waiting times and judgmental, disrespectful, and discriminatory behavior from staff and providers because of their race and public assistance status. CONCLUSIONS: Current proposals to solve the dental access problem probably will be insufficient until barriers identified by caregivers are addressed. PMID- 11772762 TI - Population attributable fractions of psychiatric disorders and behavioral outcomes associated with combat exposure among US men. AB - OBJECTIVES: This study determined the percentage of adverse outcomes in US men attributable to combat exposure. METHODS: Standardized psychiatric interviews (modified Diagnostic Interview Schedule and Composite International Diagnostic Interview assessments) were administered to a representative national sample of 2583 men aged 18 to 54 in the National Comorbidity Survey part II subsample. RESULTS: Adjusted attributable fraction estimates indicated that the following were significantly attributable to combat exposure: 27.8% of 12-month posttraumatic stress disorder, 7.4% of 12-month major depressive disorder, 8% of 12-month substance abuse disorder, 11.7% of 12-month job loss, 8.9% of current unemployment, 7.8% of current divorce or separation, and 21% of current spouse or partner abuse. CONCLUSIONS: Combat exposure results in substantial morbidity lasting decades and accounts for significant and multifarious forms of dysfunction at the national level. PMID- 11772764 TI - Ages at initiation of cigarette smoking and quit attempts among women: a generation effect. AB - OBJECTIVES: This study sought to determine whether the age at initiation of regular cigarette smoking and the likelihood of quitting smoking through age 35 differ among women from younger versus older generations. METHODS: Annual population-based, random surveys (total of 3676 female residents of Geneva, Switzerland, aged 35-74 years) were conducted from 1992 to 1998. RESULTS: Women younger than 55 years were more likely to be past or current smokers, began smoking earlier (median age < 20 years), and smoked more cigarettes per day than older women, yet attempted to quit smoking more often before age 35 (log-rank P <.001). CONCLUSIONS: Young female smokers have a higher propensity to quit smoking compared with older women. Encouraging young smokers to quit-in addition to preventing nonsmokers from starting-may be an important facet of reducing cigarette smoking prevalence among adolescents. PMID- 11772763 TI - Geographic socioeconomic status, race, and advanced-stage breast cancer in New York City. AB - OBJECTIVES: This study examined the association between a residential area' socioeconomic status (SES), race, and advanced-stage breast cancer in New York City. METHODS: The cross-sectional study design used breast cancer information for 37 921 cases diagnosed in New York City from 1986 to 1995. Residential education and income levels were based on the 1990 census and ascribed to each case by zip code. Associations between race, area SES, and advanced-stage breast cancer stage, and the interaction between race and SES, were evaluated in bivariate and multivariate analyses. RESULTS: After adjusting for age and year at diagnosis, living in areas with lower levels of education and income increased the odds of presenting with advanced-stage breast cancer by 50% for Black women and by 75% for White women. No significant qualitative interaction was present between area SES and race. CONCLUSIONS: This study confirmed independent racial and socioeconomic differences in the risk of advanced-stage breast cancer in a large and diverse population. The results emphasize the need to improve screening practices and clinical treatment in both high-risk populations and high-risk geographic areas. PMID- 11772765 TI - Bar and club tobacco promotions in the alternative press: targeting young adults. AB - OBJECTIVES: This study examined changes in tobacco promotions in the alternative press in San Francisco and Philadelphia from 1994 to 1999. METHODS: A random sample of alternative newspapers was analyzed, and a content analysis was conducted. RESULTS: Between 1994 and 1999, numbers of tobacco advertisements increased from 8 to 337 in San Francisco and from 8 to 351 in Philadelphia. Product advertisements represented only 45% to 50% of the total; the remaining advertisements were entertainment-focused promotions, mostly bar-club and event promotions. CONCLUSIONS: The tobacco industry has increased its use of bars and clubs as promotional venues and has used the alternative press to reach the young adults who frequent these establishments. This increased targeting of young adults may be associated with an increase in smoking among this group. PMID- 11772766 TI - Incomplete birth certificates: a risk marker for infant mortality. AB - OBJECTIVES: This study assessed the relationship between incomplete birth certificates and infant mortality. METHODS: Birth certificates from California (n = 538 945) were assessed in regard to underreporting of 13 predictors of perinatal outcomes and mortality. RESULTS: Of the birth certificates studied, 7.25% were incomplete. Underreporting was most common in the case of women at high risk for poor perinatal outcomes and infants dying within the first day. Increasing numbers of unreported items were shown to be associated with corresponding increases in neonatal and postneonatal mortality rates. CONCLUSIONS: Incomplete birth certificates provide an important marker for identifying high-risk women and vulnerable infants. Because data "cleaning" will result in the removal of mothers and infants at highest risk, birth certificate analyses should include incomplete records. PMID- 11772767 TI - Use of highly active antiretroviral therapy in a cohort of HIV-seropositive women. AB - OBJECTIVES: This study examined longitudinal trends in use of highly active antiretroviral therapy (HAART) among a cohort of HIV-positive participants in the Women' Interagency HIV Study. METHODS: Beginning in 1994, 1690 HIV-positive women reported detailed information about their use of antiretroviral therapy at 6 month study visits. Multivariate logistic and Cox regression analyses were used to estimate the likelihood of antiretroviral therapy and HAART use among women with study visits preceding and following HAART availability. RESULTS: Before the availability of HAART, the cohort' likelihood of any antiretroviral therapy use was associated with clinical indicators (CD4 count, viral load, symptom presence) as well as behavioral factors (abstaining from drug and alcohol use, participating in clinical trials). After HAART became commercially available, newly emerging predictors included college education, private insurance, absence of injection drug use history, and not being African American. CONCLUSIONS: After the penetration of HAART into this cohort, additional differences emerged between HAART users and nonusers. These findings can inform public health efforts to enhance women' access to the most effective types of therapy. PMID- 11772768 TI - Medical checkups: who does not get them? AB - OBJECTIVES: This study determined which predisposing, enabling, need, behavioral, and disease factors predict the use of medical checkups. METHODS: The Behavioral Risk Factor Surveillance System was used to obtain state estimates in Iowa. RESULTS: A decreased likelihood of recent checkups was noted for persons aged 25 to 44, men, and those who faced cost barriers. An increased likelihood of recent checkups was associated with married people, highest household income, health insurance, fair and poor health status, physical exercise, occasional smoking, and some chronic diseases. CONCLUSIONS: A profile of persons not having a checkup in the past 12 months emerged from the investigation. PMID- 11772769 TI - Adequacy of treatment for serious mental illness in the United States. AB - OBJECTIVES: The purpose of this study was to assess the prevalence and correlates of treatment for serious mental illness. METHODS: Data were derived from the National Comorbidity Survey, a cross-sectional, nationally representative household survey assessing the presence and correlates of mental disorders and treatments. Crude and adjusted likelihoods of receiving treatment for serious mental illness in the previous 12 months were calculated. RESULTS: Forty percent of respondents with serious mental illness had received treatment in the previous year. Of those receiving treatment, 38.9% received care that could be considered at least minimally adequate, resulting in 15.3% of all respondents with serious mental illness receiving minimally adequate treatment. Predictors of not receiving minimally adequate treatment included being a young adult or an African American, residing in the South, being diagnosed as having a psychotic disorder, and being treated in the general medical sector. CONCLUSIONS: Inadequate treatment of serious mental illness is an enormous public health problem. Public policies and cost-effective interventions are needed to improve both access to treatment and quality of treatment. PMID- 11772770 TI - Income inequality and mortality in US counties: does minority racial concentration matter? AB - This study examined (1) the relationship between income inequality and mortality among all counties in the contiguous United States to ascertain whether the relationships found for states and metropolitan areas extend to smaller geographic units and (2) the influence of minority racial concentration on the inequality-mortality linkage. METHODS: This county-level ecologic analysis used data from the Compressed Mortality Files and the US Census. Weighted least squares regression models of age-, sex-, and race-adjusted county mortality rates were estimated to examine the additive and interactive effects of income inequality and minority racial concentration. RESULTS: Higher income inequality at the county level was significantly associated with higher total mortality. Higher minority racial concentration also was significantly related to higher mortality and interacted with income inequality. CONCLUSIONS: The relationship between income inequality and mortality is robust for counties in the United States. Minority concentration interacts with income inequality, resulting in higher mortality in counties with low inequality and a high percentage of Blacks than in counties with high inequality and a high percentage of Blacks. PMID- 11772771 TI - Organizational justice: evidence of a new psychosocial predictor of health. AB - OBJECTIVES: This study examined the justice of decision-making procedures and interpersonal relations as a psychosocial predictor of health. METHODS: Regression analyses were used to examine the relationship between levels of perceived justice and self-rated health, minor psychiatric disorders, and recorded absences due to sickness in a cohort of 506 male and 3570 female hospital employees aged 19 to 63 years. RESULTS: The odds ratios of poor self rated health and minor psychiatric disorders associated with low vs high levels of perceived justice ranged from 1.7 to 2.4. The rates of absence due to sickness among those perceiving low justice were 1.2 to 1.9 times higher than among those perceiving high justice. These associations remained significant after adjustment for behavioral risks, workload, job control, and social support. CONCLUSIONS: Low organizational justice is a risk to the health of employees. PMID- 11772773 TI - Touched by homelessness: an examination of hospitality for the down and out. AB - OBJECTIVES: This study investigated patterns of "doubled-up" homelessness using an indirect measure based on host households. METHODS: In random household telephone surveys conducted in Alabama between 1990 and 2000 and nationally in 1997, respondents indicated whether any individual had stayed with them during the past year because that person was homeless. RESULTS: The percentage of Alabama households providing shelter during the past year declined from 16.2% in 1990 to 7.1% in 2000. The national rate for providing shelter in 1997 was 18.0%. CONCLUSIONS: Many households provide shelter to people to prevent them from being literally homeless. As the economy has expanded, these rates have declined in Alabama. PMID- 11772772 TI - Effect of an STD/HIV behavioral intervention on women's use of the female condom. AB - OBJECTIVES: This study assessed the effectiveness of a sexually transmitted disease (STD)/HIV behavior change intervention in increasing women's use of the female condom. METHODS: A total of 604 women at high risk for STDs and HIV in New York City, Baltimore, Md, and Seattle, Wash, enrolled in a randomized controlled trial of a small-group, skills-training intervention that included information and skills training in the use of the female condom. RESULTS: In a logistic regression, the strongest predictors of use were exposure to the intervention (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 2.8, 10.7), intention to use the female condom in the future (OR = 4.5; 95% CI = 2.4, 8.5), having asked a partner to use a condom in the past 30 days (OR = 2.3; 95% CI = 1.3, 3.9), and confidence in asking a partner to use a condom (OR = 1.9; 95% CI = 1.1, 3.5). CONCLUSIONS: Clinicians counseling women in the use of the female condom need to provide information, demonstrate its correct use with their clients, and provide an opportunity for their clients to practice skills themselves. PMID- 11772774 TI - Deregionalization of neonatal intensive care in urban areas. AB - OBJECTIVES: This report describes the extent of deregionalization of neonatal intensive care in urban areas of the United States in the 1980s and 1990s and the factors associated with it. METHODS: We conducted a 15-year retrospective analysis of secondary data from US metropolitan statistical areas. Primary outcome measures are number of neonatal intensive care unit (NICU) beds, number of NICU hospitals, and number of small NICUs. RESULTS: Growth in the supply of NICU care has outpaced the need. During the study period (1980-1995), the number of hospitals grew by 99%, the number of NICU beds by 138%, and the number of neonatologists by 268%. In contrast, the growth in needed bed days was only 84%. Of greater concern, the number of beds in small NICU facilities continues to grow. Local regulatory and practice characteristics are important in explaining this growth. CONCLUSIONS: Local policymakers should examine the factors that facilitate the proliferation of services, especially the development of small NICUs. Policies that encourage cooperative efforts by hospitals should be developed. Eliminating small NICUs would not restrict the NICU bed supply in most metropolitan statistical areas. PMID- 11772775 TI - Defining early adolescent childbearing. AB - OBJECTIVES: This study determined the age group for the case definition of early adolescent childbearing based on rates of adverse clinical outcomes. METHODS: We examined rates of infant mortality, very low birthweight (<1500 g), and very preterm delivery (<32 weeks) per 1000 live births for all US singleton first births (n = 768 029) to women aged 12 to 23 years in the 1995 US birth cohort. RESULTS: Rates of infant mortality, very low birthweight, and very preterm delivery were graphed by maternal age. In all 3 cases, the inflection point below which the rate of poor birth outcome is lower and begins to stabilize is at 16 years; therefore, mothers 15 years and younger were grouped together to determine the case definition of early adolescent childbearing. The inflection points were similar when outcomes were stratified by the 3 largest US racial/ethnic groups (non-Hispanic White, non-Hispanic Black, and Mexican American). CONCLUSIONS: From this population-based analysis of birth outcomes, we conclude that early adolescent childbearing is best defined as giving birth at 15 years or younger. PMID- 11772777 TI - Effects of air pollution on daily clinic visits for lower respiratory tract illness. AB - The authors used data obtained from clinic records and environmental monitoring stations in Taiwan during 1998 to estimate the association between air pollution and daily numbers of clinic visits for lower respiratory tract illness. A small area design and hierarchical modeling were used for the analysis. Rates of daily clinic visits were associated with current-day concentrations of nitrogen dioxide, carbon monoxide, sulfur dioxide, and particulate matter less than or equal to 10 microm in aerometric diameter. People over age 65 years were the most susceptible, and estimated pollution effects decreased as the exposure time lag increased. The analysis also suggested that several community-specific variables, such as a community's population density and yearly air pollution levels, modified the effects of air pollution. In this paper, the authors demonstrate the use of a small-area design to assess acute health effects of air pollution. PMID- 11772778 TI - Invited commentary: air pollution and health-what can we learn from a hierarchical approach? PMID- 11772780 TI - Ambient air pollution and risk of birth defects in Southern California. AB - The authors evaluated the effect of air pollution on the occurrence of birth defects ascertained by the California Birth Defects Monitoring Program in neonates and fetuses delivered in southern California in 1987-1993. By using measurements from ambient monitoring stations of carbon monoxide (CO), nitrogen dioxide, ozone, and particulate matter <10 microm in aerodynamic diameter, they calculated average monthly exposure estimates for each pregnancy. Conventional, polytomous, and hierarchical logistic regression was used to estimate odds ratios for subgroups of cardiac and orofacial defects. Odds ratios for cardiac ventricular septal defects increased in a dose-response fashion with increasing second-month CO exposure (odds ratio (OR)(2nd quartile) CO = 1.62, 95% confidence interval (CI): 1.05, 2.48; OR(3rd quartile) CO = 2.09, 95% CI: 1.19, 3.67; OR(4th quartile) CO = 2.95, 95% CI: 1.44, 6.05). Similarly, risks for aortic artery and valve defects, pulmonary artery and valve anomalies, and conotruncal defects increased with second-month ozone exposure. The study was inconclusive for other air pollutants. The authors' results are supported by the specificity of the timing of the effect and some evidence from animal data; however, this is the first known study to link ambient air pollution during a vulnerable window of development to human malformations. Confirmation by further studies is needed. PMID- 11772781 TI - Maternal medication use and risks of gastroschisis and small intestinal atresia. AB - Gastroschisis and small intestinal atresia (SIA) are birth defects that are thought to arise from vascular disruption of fetal mesenteric vessels. Previous studies of gastroschisis have suggested that risk is increased for maternal use of vasoactive over-the-counter medications, including specific analgesics and decongestants. This retrospective study evaluated the relation between maternal use of cough/cold/analgesic medications and risks of gastroschisis and SIA. From 1995 to 1999, the mothers of 206 gastroschisis cases, 126 SIA cases, and 798 controls in the United States and Canada were interviewed about medication use and illnesses. Risks of gastroschisis were elevated for use of aspirin (odds ratio = 2.7, 95% confidence interval: 1.2, 5.9), pseudoephedrine (odds ratio = 1.8, 95% confidence interval: 1.0, 3.2), acetaminophen (odds ratio = 1.5, 95% confidence interval: 1.1, 2.2), and pseudoephedrine combined with acetaminophen (odds ratio = 4.2, 95% confidence interval: 1.9, 9.2). Risks of SIA were increased for any use of pseudoephedrine (odds ratio = 2.0, 95% confidence interval: 1.0, 4.0) and for use of pseudoephedrine in combination with acetaminophen (odds ratio = 3.0, 95% confidence interval: 1.1, 8.0). Reported fever, upper respiratory infection, and allergy were not associated with risks of either defect. These findings add more evidence that aspirin use in early pregnancy increases risk of gastroschisis. Although pseudoephedrine has previously been shown to increase gastroschisis risk, findings of this study raise questions about interactions between medications and possible confounding by underlying illness. PMID- 11772782 TI - Maternal serum caffeine metabolites and small-for-gestational age birth. AB - To determine whether the third-trimester maternal serum concentration of paraxanthine, caffeine's primary metabolite, is associated with delivery of a small-for-gestational age infant (birth weight less than the 10th percentile for gestational age, gender, and ethnicity) and whether this association differs by smoking, the authors studied 2,515 women who participated in the Collaborative Perinatal Project from 1959 to 1966. The women provided a third-trimester serum sample and had been controls for a nested case-control study of spontaneous abortion. The mean serum paraxanthine concentration was greater in women who gave birth to small-for-gestational age infants (754 ng/ml) than to appropriately grown infants (653 ng/ml, p = 0.02). However, the linear trend for increasing serum paraxanthine concentration to be associated with increasing risk of small for-gestational age birth was confined to women who also smoked (p = 0.03). There was no association between paraxanthine and fetal growth in nonsmokers (p = 0.48). Adjustment for maternal age, pre-pregnant weight, education, parity, ethnicity, and the number of cigarettes smoked per day did not alter the results substantially, although the p value for trend among smokers increased to 0.07. The authors conclude that maternal third-trimester serum paraxanthine concentration, which reflects caffeine consumption, was associated with a higher risk of reduced fetal growth, particularly among women who smoked. PMID- 11772783 TI - Risk factors for progression of common carotid atherosclerosis: the Atherosclerosis Risk in Communities Study, 1987-1998. AB - Intima-media thickness of the common carotid arteries is a marker of atherosclerosis and has been shown to be associated with prevalent and incident coronary heart disease and with coronary heart disease risk factors. The authors examined the association of baseline risk factors or change in risk factors with change in intima-media thickness over follow-up (1987-1998) in the Atherosclerosis Risk in Communities (ARIC) population-based cohort (baseline: age 45-64 years, n = 15,792). Subjects were members of households sampled in four areas of the United States. Either not adjusting for baseline intima-media thickness or doing so with correction for its measurement error resulted in statistically significant associations of change in intima-media thickness with baseline diabetes, current smoking, high density lipoprotein cholesterol, pulse pressure, white blood cell count, and fibrinogen. The associations were of a similar order of magnitude as anticipated from the authors' cross-sectional findings. Statistically significant associations were found between change in intima-media thickness and change in low density lipoprotein cholesterol and triglycerides and with onset of diabetes and hypertension. In summary, established risk factors for coronary heart disease are associated with the rate of change of subclinical atherosclerosis. PMID- 11772784 TI - Does the cardiac autonomic response to postural change predict incident coronary heart disease and mortality? The Atherosclerosis Risk in Communities Study. AB - This study evaluated whether small shifts in cardiac autonomic balance with standing, as measured by heart rate variability (HRV), were prospectively associated with incident coronary heart disease (CHD) and mortality. Both Black and White men and women aged 45-64 years from the Atherosclerosis Risk in Communities Study (n = 9,267) were followed from 1987 to 1997 for myocardial infarction (n = 296), fatal CHD (n = 63), and non-CHD mortality (n = 533). HRV indices and mean R-R interval length (inverse of heart rate) were measured in the supine and standing positions for 2 minutes each; HRV shift was calculated as the difference between positions. After adjustment for demographic characteristics and medication use, HRV in each position was significantly inversely related to events in Cox proportional hazards models. With the exception of R-R interval length shift and myocardial infarction (hazard ratio = 1.42, 95% confidence interval: 1.02, 1.98 for the smallest vs. the largest quartile), there was no association between HRV shift and the other events. Despite clinical research suggesting that HRV shift with standing is a more sensitive measure of autonomic balance than is HRV in one position, simple measures such as heart rate change and supine and standing HRV were better predictors of events. PMID- 11772785 TI - Leukocyte count, erythrocyte sedimentation rate, and diabetes incidence in a national sample of US adults. AB - Emerging data suggest that inflammation may play a role in the etiology of diabetes mellitus. Because few prospective studies have addressed this issue, the author examined the relation between leukocyte count and erythrocyte sedimentation rate and diabetes incidence using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (from 1971-1975 to 1992-1993). Of 8,352 participants included in the analysis, 878 developed incident diabetes during the approximately 20-year follow-up. After adjustment for age, smoking status, systolic blood pressure, cholesterol concentration, use of antihypertensive medication, recreational exercise, non-recreational activity, alcohol use, and body mass index, the hazard ratios from proportional hazards for participants with a leukocyte count of > or = 9.1 x 10(9)/liter compared with participants with a leukocyte count of < or = 5.7 x 10(9)/liter were 1.33 (95% confidence interval (CI): 0.81, 2.19) for men and 1.68 (95% CI: 1.21, 2.34) for women. The adjusted hazard ratios for participants with an erythrocyte sedimentation rate of > or = 26 mm/hour compared with participants with an erythrocyte sedimentation rate of < or = 5 mm/hour were 1.85 (95% CI: 0.97, 3.54) for men and 0.83 (95% CI: 0.47, 1.44) for women. These results provide limited support to the hypothesis that inflammation is an etiologic factor for diabetes. PMID- 11772786 TI - Associations of serum C-reactive protein with fasting insulin, glucose, and glycosylated hemoglobin: the Third National Health and Nutrition Examination Survey, 1988-1994. AB - This study investigated the associations between serum C-reactive protein and fasting blood levels of insulin, glucose, and hemoglobin A1c (HbA1c). Data from the Third National Health and Nutrition Examination Survey (1998-1994) were used. Study subjects included 2,466 men and 2,876 women who were > or = 17 years and nondiabetics with an overnight fast for blood draw. C-reactive protein was categorized into low (<0.3 mg/dl), moderate (0.3-0.9 mg/dl), and high (> or = 1.0 mg/dl) levels. Mean levels of insulin, glucose, and HbA1c were compared across C reactive protein levels after adjustment for age, ethnicity, education, poverty index, cigarette smoking, alcohol use, and leisure time physical activity. For men with low (n = 1,818), moderate (n = 493), and high (n = 155) C-reactive protein, the adjusted means of insulin were 9.4, 11.7, and 10.5 microunits/ml (p < 0.01); glucose, 99.8, 101.6, and 100.6 mg/dl (p > 0.05); and HbA1c, 5.4%, 5.5%, and 5.5% (p < 0.05). For women with low (n = 1,816), moderate (n = 776), and high (n = 282) C-reactive protein, the adjusted means of insulin were 8.7, 11.2, and 13.7 microunits/ml (p < 0.01); glucose, 95.3, 97.9, and 105.2 mg/dl (p < 0.01); and HbA1c, 5.3%, 5.4%, and 5.6% (p < 0.01). In conclusion, elevated C-reactive protein was associated with higher insulin and HbA1c among men and women and with higher glucose levels among women only. These results suggest a possible role of inflammation in insulin resistance and glucose intolerance. PMID- 11772787 TI - Smoking cessation and risk of cataract extraction among US women and men. AB - Although the observational evidence linking cigarette smoking with risk of senile cataract is well-established, it is unclear whether any benefit is obtained from quitting smoking. Therefore, in this study, the authors examined the association between time since quitting smoking and incidence of cataract extraction in women and men enrolled in the Nurses' Health Study and the Health Professionals Follow up Study, respectively. There were 4,281 incident physician-confirmed cases of cataract and 1,038,493 accumulated person-years of follow-up. Compared with current smokers, former smokers who had quit smoking 25 or more years previously had a 20% lower risk of cataract extraction after adjustment for age, average number of cigarettes smoked per day, and other potential risk factors (relative risk (RR) = 0.80, 95% confidence interval (CI): 0.71, 0.91). However, risk among past smokers did not decrease to the level seen among never smokers (for never smokers, RR = 0.64, 95% CI: 0.52, 0.79). The observed relation was similar when data were examined by cataract subtype (>25 years since quitting vs. current smoking: primarily nuclear cataract, RR = 0.82, 95% CI: 0.68, 0.97; primarily posterior subcapsular cataract, RR = 0.90, 95% CI: 0.71, 1.13). These findings suggest that any healing from damage due to cigarette smoking occurs at a very modest pace, and they emphasize the importance of never starting to smoke or quitting early in life. PMID- 11772788 TI - Temperature and mortality in 11 cities of the eastern United States. AB - Episodes of extremely hot or cold temperatures are associated with increased mortality. Time-series analyses show an association between temperature and mortality across a range of less extreme temperatures. In this paper, the authors describe the temperature-mortality association for 11 large eastern US cities in 1973-1994 by estimating the relative risks of mortality using log-linear regression analysis for time-series data and by exploring city characteristics associated with variations in this temperature-mortality relation. Current and recent days' temperatures were the weather components most strongly predictive of mortality, and mortality risk generally decreased as temperature increased from the coldest days to a certain threshold temperature, which varied by latitude, above which mortality risk increased as temperature increased. The authors also found a strong association of the temperature-mortality relation with latitude, with a greater effect of colder temperatures on mortality risk in more-southern cities and of warmer temperatures in more-northern cities. The percentage of households with air conditioners in the south and heaters in the north, which serve as indicators of socioeconomic status of the city population, also predicted weather-related mortality. The model developed in this analysis is potentially useful for projecting the consequences of climate-change scenarios and offering insights into susceptibility to the adverse effects of weather. PMID- 11772789 TI - Regression analysis of multiple-source longitudinal outcomes: a "Stirling County" depression study. AB - Epidemiologic studies of psychiatric disorders have increasingly relied on multiple sources of information to improve the validity of diagnoses and repeated assessments over time to provide a longitudinal perspective. In this paper, the authors present a general multivariate logistic regression method for the simultaneous analysis of discrete outcomes that exhibit such features. This approach permits risk factor and agreement analyses within a unified framework and appropriately uses data from subjects who may be missing some outcomes. The authors use this approach to analyze data from a "Stirling County" study of depression. During a 3- to 4-year period in the early 1990s, 631 subjects were assessed in two separate interviews, on each occasion with two diagnostic schedules (the DePression and AnXiety schedule (DPAX) and the Diagnostic Interview Schedule (DIS)). The female:male ratio of depression was found to be different for the DPAX and the DIS (0.8 and 1.6, respectively). Education was inversely associated with depression, while the effects of time, the subject's age, and the interviewer's sex were essentially null. With respect to the outcomes' association, agreement between the DPAX and the DIS was low. In addition, stability of the DPAX over time was significantly higher than that of the DIS. No covariates were found to affect significantly the association between outcomes. PMID- 11772790 TI - Do interviewers' health beliefs and habits modify responses to sensitive questions? A study using data Collected from pregnant women by means of computer assisted telephone interviews. AB - If interviewers' personal habits or attitudes influence respondents' answers to given questions, this may lead to bias, which should be taken into consideration when analyzing data. The authors examined a potential interviewer effect in a study of pregnant women in which exposure data were obtained through computer assisted telephone interviews. The authors compared interviewer characteristics for 34 interviewers with the responses they obtained in 12,910 interviews carried out for the Danish National Birth Cohort Study. Response data on smoking and alcohol consumption in the first trimester of pregnancy were collected during the time period October 1, 1997-February 1, 1999. Overall, the authors found little evidence to suggest that interviewers' personal habits or attitudes toward smoking and alcohol consumption during pregnancy had consequences for the responses they obtained; neither did the interviewers' education, age, or parity correlate with the answers they obtained. In these data gathered through computer assisted telephone interviews, interviewer effects arising from variations in interviewers' health beliefs and personal habits were found to be negligible. Thorough training of the interviewers and continuous supervision may have contributed to this finding. PMID- 11772791 TI - Pediatric clinical trials: shall we take a lead? PMID- 11772792 TI - The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. AB - Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and informed consent, 165 coronary artery bypass graft surgery patients were studied. Patients received similar surgical and anesthetic management until rewarming from hypothermic (28 degrees -32 degrees C) CPB. Group 1 (control; n = 100) was warmed in a conventional manner (4 degrees -6 degrees C gradient between nasopharyngeal and CPB perfusate temperature) whereas Group 2 (slow rewarm; n = 65) was warmed at a slower rate, maintaining no more than 2 degrees C difference between nasopharyngeal and CPB perfusate temperature. Neurocognitive function was assessed at baseline and 6 wk after coronary artery bypass graft surgery. Univariable analysis revealed no significant differences between the Control and Slow Rewarming groups in the stroke rate. Multivariable linear regression analysis, examining treatment group, diabetes, baseline cognitive function, and cross-clamp time revealed a significant association between change in cognitive function and rate of rewarming (P = 0.05). IMPLICATIONS: Slower rewarming during cardiopulmonary bypass (CPB) was associated with better cognitive performance at 6 wk. These results suggest that a slower rewarming rate with lower peak temperatures during CPB may be an important factor in the prevention of neurocognitive decline after hypothermic CPB. PMID- 11772793 TI - The effects of three different analgesia techniques on long-term postthoracotomy pain. AB - In this clinical, randomized, prospective study, we compared the effects of three different analgesia techniques (thoracic epidural analgesia [TEA] with and without preoperative initiation and IV patient-controlled analgesia [IV-PCA]) on postthoracotomy pain in 69 patients. In two groups, a thoracic epidural catheter was inserted preoperatively. Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively. Postoperative analgesia was maintained with epidural PCA with a similar solution. Group Post-TEA, with no intraoperative medication, had the same postoperative analgesia as Group Pre-TEA plus the bolus dose. Group IV-PCA received only IV-PCA with morphine for postoperative analgesia. Pain was evaluated every 4 h during the first 48 h at rest, cough, and movement. Pre-TEA was associated with decreased pain compared with the other groups. Six months later, the patients were asked about their pain. The incidence and the intensity of pain were most frequent in Group IV-PCA (78%) and were the least in Group Pre-TEA (45%) (Group Pre-TEA versus Group IV-PCA, P = 0.0233; Group Pre-TEA versus Group IV-PCA, P = 0.014). Patients having pain on the second postoperative day had 83% chronic pain. TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain. IMPLICATIONS: Preoperatively initiated thoracic epidural analgesia has the most satisfying results in controlling postthoracotomy pain in the acute and long-term period, and it is associated with a decreased incidence (and intensity) of chronic pain compared with postoperative (epidural or IV) analgesia. Chronic pain has an incidence of 62%. PMID- 11772794 TI - Heart rate variability and arterial blood pressure variability show different characteristic changes during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs. AB - We assessed the changes in heart rate variability (HRV) and blood pressure variability (BPV) as indices of autonomic nervous system and volume status during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs. Nine dogs were used. They were sequentially subjected to withdrawal of 30% estimated blood volume and graded isoflurane inhalation of 1% and 2% followed by discontinuation of isoflurane and retransfusion. The power spectra of HRV and BPV were computed using the fast Fourier transformation, and were quantified by determining the areas of the spectrum in two component widths: low-frequency component (LF) (0.04 0.15 Hz) and high-frequency component (HF) (0.15-0.4 Hz). During hemorrhage and isoflurane anesthesia, both HRV-LF and HRV-HF were decreased and plateaued at the smaller concentration of isoflurane, whereas BPV-LF decreased concentration dependently. BPV-HF showed a completely different response and increased significantly during 2% isoflurane. We speculate that HRV and BPV-LF would be affected by the autonomic nervous activity, whereas BPV-HF would depend on relative/absolute change in circulating blood volume. IMPLICATIONS: Power spectra of heart rate variability (HRV) and blood pressure variability (BPV) were computed using the fast Fourier transformation. The HRV and BPV showed their differential characteristics during hemorrhage, isoflurane anesthesia, and retransfusion, and would help to assess changes in autonomic nervous system and preload under mechanical ventilation. PMID- 11772795 TI - The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting. AB - Acute deterioration in ventricular function and oxygen transport is common after cardiac surgery. We hypothesized that milrinone or amrinone may reduce their occurrence and catecholamine requirements and increase cellular enzyme levels in patients undergoing coronary artery bypass. In 45 patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg x kg(-1) x min(-1) infusion for 10 h, amrinone 1.5 mg/kg plus 10 microg x kg(-1) x min(-1) infusion for 10 h, or placebo at release of aortic cross-clamp. Hemodynamic variables, dopamine requirement, and laboratory values were recorded. At the postoperative nadir, stroke volume index was higher in the Milrinone and Amrinone groups (mean +/- SD, 27.8 +/- 4.0 and 26.1 +/- 3.2 vs. 20.4 +/- 5.1 mL x min (-1) x m(-2) per beat, P < 0.0001), and oxygen transport index was higher (354.7 +/- 57.8 and 353.7 +/- 91.2 vs 283.0 +/- 83.9 mL. min(-1) x m(-2), P = 0.009). The postoperative dopamine requirement was less (6.6 +/- 2.7 and 6.8 +/- 2.6 vs 10.4 +/- 2.0 mg/kg, P < 0.008), and postoperative serum lactate, alanine and aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, C-reactive protein, and glucose levels were less (P < 0.01). The mean postoperative heart rate was faster in the Milrinone group than in the Amrinone and Placebo groups (96.8 +/- 10.3 vs. 86.9 +/- 9.5 and 87.8 +/- 10.8 bpm, P < 0.01). Milrinone and amrinone administered preemptively reduce postoperative deterioration in cardiac function and oxygen transport, dopamine requirement, and increases in serum lactate, glucose, and enzyme levels, although milrinone may increase heart rate. IMPLICATIONS: Preemptive milrinone or amrinone administration before separation from cardiopulmonary bypass in cardiac surgical patients not only ameliorates postoperative deterioration in cardiac function and oxygen transport, but also reduces dopamine requirement and increases serum lactate, glucose, and cellular enzyme levels, although milrinone may increase heart rate. PMID- 11772796 TI - Oral midazolam premedication in preadolescents and adolescents. AB - We sought to determine the influence of preoperative oral midazolam on 1) sedation score, 2) measures of anesthetic emergence, 3) recovery times, and 4) bispectral index (BIS) measurements during sevoflurane/N(2)O anesthesia in adolescent patients. Fifty ASA I and II patients 10-18 yr of age were enrolled in a prospective double-blinded study. Patients were randomized to receive either 20 mg of midazolam (M group) or midazolam vehicle (P group) as premedication. Before the induction, sedation scores and BIS values were determined in all patients. After inhaled induction and intubation, expired sevoflurane was stabilized at 3% in 60% N(2)O and the corresponding BIS (BIS I) recorded. Upon completion of surgery, sevoflurane was stabilized at 0.5% and the BIS (BIS E) again recorded. Plasma midazolam levels were measured at the time of BIS I and BIS E. There were no significant differences between groups in awakening time, sevoflurane/N(2)O awakening concentrations, time to postanesthesia care unit discharge, or BIS I and BIS E measurements. Sedation scores and preinduction BIS values were significantly lower in Group M than in Group P, although only 40% of midazolam treated patients exhibited detectable sedation, with marked interindividual variability in achieved plasma midazolam levels. Detectable preoperative sedation was predictive of delayed emergence. IMPLICATIONS: We demonstrated a measurable sedative effect of oral midazolam in adolescents which correlated with simultaneous bispectral index (BIS) measurement. Considering the overall group, midazolam premedication did not affect intraoperative BIS, emergence times, or recovery times compared with placebo controls. Detectable preoperative sedation, and not merely midazolam administration, was predictive of prolonged emergence. PMID- 11772797 TI - A comparison of three doses of a commercially prepared oral midazolam syrup in children. AB - Midazolam is widely used as a preanesthetic medication for children. Prior studies have used extemporaneous formulations to disguise the bitter taste of IV midazolam and to improve patient acceptance, but with unknown bioavailability. In this prospective, randomized, double-blinded study we examined the efficacy, safety, and taste acceptability of three doses (0.25, 0.5, and 1.0 mg/kg, up to a maximum of 20 mg) of commercially prepared Versed((R)) syrup (midazolam HCl) in children stratified by age (6 mo to <2 yr, 2 to <6 yr, and 6 to <16 yr). All children were ASA class I-III scheduled for elective surgery. Subjects were continuously observed and monitored with pulse oximetry. Ninety-five percent of patients accepted the syrup, and 97% demonstrated satisfactory sedation before induction. There was an apparent relationship between dose and onset of sedation and anxiolysis (P < 0.01). Eight-eight percent had satisfactory anxiety ratings at the time of attempted separation from parents, and 86% had satisfactory anxiety ratings at face mask application. The youngest age group recovered earlier than the two older age groups (P < 0.001). There was no relationship between midazolam dose and duration of postanesthesia care unit stay. Before induction, there were no episodes of desaturation, but there were two episodes of nausea and three episodes of emesis. At the time of induction, during anesthesia, and in the postanesthesia care unit, there were several adverse respiratory events. Oral midazolam syrup is effective for producing sedation and anxiolysis at a dose of 0.25 mg/kg, with minimal effects on respiration and oxygen saturation even when administered at doses as large as 1.0 mg/kg (maximum, 20 mg) as the sole sedating medication to healthy children in a supervised clinical setting. IMPLICATIONS: Commercially prepared oral midazolam syrup is effective in producing sedation and anxiolysis in doses as small as 0.25 mg/kg; there is a slightly faster onset with increasing the dose to 1.0 mg/kg. At all doses, 97% of patients demonstrated satisfactory sedation, whereas 86% demonstrated satisfactory anxiolysis when the face mask was applied. PMID- 11772798 TI - The pharmacokinetics of epsilon-aminocaproic acid in children undergoing surgical repair of congenital heart defects. AB - epsilon-Aminocaproic acid (epsilonACA) is often administered to children undergoing cardiac surgery by using empiric dosing techniques. We hypothesized that children would have different pharmacokinetic variables and require a dosing scheme different from adults to maintain stable and effective serum epsilonACA concentrations. Eight patients were enrolled in our study. epsilonACA 50 mg/kg was administered three times IV: before, during, and after cardiopulmonary bypass (CPB). Nine serum samples were obtained. epsilonACA plasma concentrations were measured by using high-performance liquid chromatography, and pharmacokinetic modeling was done by using NONMEM. The best fit was seen with a two-compartment model with volume of distribution (V(1)) adjusted for weight and CPB. Compared with published results in adults, modeling suggests that weight-adjusted V(1) is larger in children than in adults before, during, and after CPB. Clearance from the central compartment (k(10)) was also greater in children than adults, and declined during CPB. Redistribution rates from the central compartment, k(12) and k(21), were greater in children and not affected by CPB. We modeled several different dosing regimens for epsilonACA based on the larger V(1), and higher redistribution and clearance variables. We conclude that, because of the developmental differences in pharmacokinetic variables of epsilonACA, when compared with adult patients, a larger initial dose and faster infusion rate as well as an addi-tional dose on CPB are needed to maintain similar concentrations. IMPLICATIONS: Pharmacokinetic modeling of epsilon-aminocaproic acid in children undergoing cardiac surgery suggests that there are developmental differences in pharmacokinetic variables. Based on these data, a dosing modification in children is suggested which may better maintain serum concentrations in children when compared with adults. PMID- 11772799 TI - Cisapride does not prevent postoperative vomiting in children. AB - The peripherally acting prokinetic drug cisapride can overcome opioid-induced gastrointestinal paresis and may thereby eliminate a stimulus for postoperative vomiting. We conducted a prospective, randomized, double-blinded, controlled trial of 96 children undergoing inguinal surgery to determine whether cisapride would reduce the incidence of postoperative vomiting after general anesthesia supplemented with morphine. Group C1 patients (n = 38) received cisapride 0.3 mg/kg orally 1 h before surgery and placebo 6 h later, Group C2 (n = 28) received cisapride both before and after surgery, and Group P (n = 30) received placebo. Mean age (5.0 +/- 2.7 yr) and weight (21.0 +/- 8.6 kg), median pain scores and parent satisfaction scores, and incidence of rescue analgesic administration were similar across groups. Contrary to our hypothesis, incidences of postoperative vomiting in the hospital (32% vs 20%, P = 0.33) and at home (53% vs 46%, P = 0.33) did not vary by treatment group (with [C1 and C2] and without [P] cisapride, respectively). There was a trend toward more severe postoperative vomiting (three or more episodes) in children who received cisapride versus those who did not, both in hospital (6% vs 0%, P = 0.3) and at home (22% vs 8%) (P = 0.13). We conclude that cisapride does not prevent postoperative vomiting in this patient population and speculate that factors other than reduced gastrointestinal motility associated with general anesthesia and opioids are more important determinants of postoperative vomiting. IMPLICATIONS: Cisapride does not prevent postoperative vomiting in children and may increase its severity. PMID- 11772800 TI - The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. AB - Nonsteroidal antiinflammatory drugs (NSAIDs) provide effective postoperative analgesia after arthroscopic knee surgery. Some investigators have suggested that the preemptive administration of NSAIDs may reduce postoperative analgesic requirements and hypersensitivity. We evaluated the analgesic effect of administering rofecoxib either before or after surgical incision in patients undergoing arthroscopic knee surgery under local anesthesia. Sixty patients undergoing arthroscopic meniscectomy were randomized into three groups. All patients received intraarticular bupivacaine 0.25% pre- and postsurgery together with IV sedation using midazolam and propofol. The Preincisional group received a single 50 mg dose of rofecoxib 1 h before surgery, the Postincisional group received rofecoxib 50 mg after the completion of surgery, and the Placebo group received a placebo tablet before surgery. Pain scores, the time to first opioid use, and 24-h analgesic use were recorded. Analgesic duration, defined as the time from completion of surgery until first opioid use, was significantly longer in those patients receiving pre- (803 +/- 536 min) versus postincisional (461 +/- 344 min) rofecoxib or placebo (318 +/- 108 min). The 24 h acetaminophen/oxycodone use was less in the Preincisional group (1.5 +/- 0.6 pills) versus the Postincisional group (3.3 +/- 1.3 pills) or the Placebo group (5.5 +/- 1.6 pills). Pain scores with movement were lower in the Preincisional group at all postoperative time intervals. We conclude that rofecoxib provides effective postoperative analgesia for arthroscopic meniscectomy. Further, the administration of rofecoxib 50 mg before surgery provides a longer duration of postoperative analgesia, less 24 h opioid use, and lower incidental pain scores compared with administering the drug after the completion of surgery. IMPLICATIONS: The administration of rofecoxib 50 mg before arthroscopic knee surgery provides a longer duration of analgesia, less 24-h opioid use, and lower pain scores than administering the drug after the completion of surgery. PMID- 11772801 TI - The assessment of postural stability after ambulatory anesthesia: a comparison of desflurane with propofol. AB - We designed this study to evaluate postural stability in outpatients after either desflurane or propofol anesthesia. After IRB approval, 120 consenting women undergoing gynecological laparoscopic procedures were randomly assigned to receive either desflurane or propofol-based general anesthesia. After surgery, patients' postural stability was measured as body sway velocity by using a computerized force platform in the following conditions: 1) standing on a firm surface with eyes open versus closed and 2) standing on a foam surface with eyes open versus closed. These measurements were made before anesthesia, immediately after the patient achieved a Post-Anesthesia Discharge Score of 9, and at actual discharge home. At the time patients first achieved a Post-Anesthesia Discharge Score of 9, the body sway in the Propofol group was significantly more than in the Desflurane group when patients were asked to stand on a foam surface with eyes closed (testing the ability of using vestibular information for balance control). We concluded that the desflurane-based anesthetic was associated with better postural control than the propofol-based anesthetic in the early recovery period after outpatient gynecological laparoscopic procedures. IMPLICATIONS: The residual effects of the short-acting general anesthetics desflurane and propofol on patient's balance function during recovery after surgery were assessed with a computerized force platform. The results showed that desflurane seemed to be associated with better postural control than propofol in the early recovery period. PMID- 11772802 TI - Ambulatory discharge after long-acting peripheral nerve blockade: 2382 blocks with ropivacaine. AB - Discharging patients with a long-acting peripheral nerve block remains controversial. Concerns about accidental injury of the limb or surgical site because of an insensate extremity are common despite a lack of data on the subject. We report a study examining the efficacy and complications of discharge after long-acting block. This prospective study included 1791 patients receiving an upper or lower extremity nerve block with 0.5% ropivacaine and discharged the day of surgery. Efficacy (conversion to general anesthesia and opioid use), persistent motor or sensory weakness, complications, satisfaction, and unscheduled health care visits were assessed in the postanesthesia care unit (PACU) and at 24 h and 7 days postoperatively using a detailed questionnaire. There were 2382 blocks placed: 1119 upper extremity blocks and 1263 lower extremity blocks. Efficacy was demonstrated by a small conversion to general anesthesia (1%-6%) and a lack of patients requiring opioids in the PACU (89% 92%). A large percentage of patients continued to use opioids at 7 days (17% 22%). Despite the requirement for opioids, satisfaction with the anesthesia experience was high at 24 h and 7 days (Liekert scale [1-5] mean at 24 h, 4.88 +/ 0.44; mean at 7 days, 4.77 +/- 0.69) and most (98%) would choose the same anesthetic again. Thirty-seven patients (1.6%) were identified with symptoms or complaints at 7 days. After review, 6 of them (0.25%) had a persistent paresthesia that may have been related to the block or discharge. We conclude that long-acting peripheral nerve blockade may be safely used in the ambulatory setting with a high degree of efficacy, safety, and satisfaction. This technique is associated with an infrequent incidence of neurologic complications and injuries. Given the frequent incidence of persistent pain at 7 days, prolongation of the analgesia would be beneficial. IMPLICATIONS: This study demonstrates that long-acting peripheral nerve blockade may be safely used in the ambulatory setting with a high degree of efficacy and satisfaction. This technique is associated with an infrequent incidence of neurologic complications and injuries despite discharge with an insensate extremity. The frequent incidence of pain at 7 days suggests that longer-acting local anesthetics are still needed. PMID- 11772803 TI - Peripheral nerve blockade with long-acting local anesthetics: a survey of the Society for Ambulatory Anesthesia. AB - Despite the growth of ambulatory anesthesia and the renewed popularity of regional techniques, there is little current information concerning outpatient regional anesthesia practices or attitudes about discharge with an insensate extremity. We present results from a survey sent to all members of the Society for Ambulatory Anesthesia (SAMBA). The survey was mailed in January 2001 to 2373 SAMBA members, along with a self-addressed stamped return envelope. After 3 mo, 1078 surveys were returned (response rate 45%). Respondents indicated that they were most likely to perform axillary (77%), interscalene (67%), and ankle blocks (68%) on ambulatory patients. They were less likely to perform lower extremity conduction blocks in ambulatory patients (femoral blocks, 40%; all other types of blocks, <23%]. Eighty-five percent of respondents discharged patients with long acting blocks, but this was mainly limited to three types. Of the 16% who never or rarely discharged patients with long-acting blocks, the primary reasons were concern about patient injury (49%) and the inability for patients to care for themselves (28%). Only 22% of office-based anesthesiologists would perform upper extremity blocks and only 28% would perform lower extremity blocks (P < 0.001). This survey demonstrates that use of regional anesthesia in outpatients is common but restricted to a few techniques. Discharge with an insensate upper extremity is prevalent but discharge with an insensate lower extremity is not common and remains controversial. Despite the reasoning for the reported practices, randomized data are necessary to confirm the validity of these concerns. IMPLICATIONS: This survey demonstrates that use of regional anesthesia in outpatients is common but restricted to a few techniques. Discharge with an insensate upper extremity is common but discharge with an insensate lower extremity is not prevalent and remains controversial. PMID- 11772804 TI - Epidural hematoma after outpatient epidural anesthesia. AB - IMPLICATIONS: Epidural hematoma is a rare complication of epidural anesthesia in healthy patients. Expedient diagnosis and treatment are essential to avoid permanent neurologic deficits. In an outpatient setting, patients should be instructed to communicate symptoms of severe back pain or weakness early. PMID- 11772805 TI - The inhibitory effects of anesthetics and ethanol on substance P receptors expressed in Xenopus oocytes. AB - The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. SP is unique to a subpopulation of C fibers found within primary afferent nerves. However, the effects of anesthetics on the SP receptor (SPR) are not clear. In this study, we investigated the effects of volatile anesthetics and ethanol on SPR expressed in Xenopus oocytes. We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on SP-induced currents mediated by SPR expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the volatile anesthetics tested, and ethanol, inhibited SPR induced Ca(2+)-activated Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C inhibitor bisindolylmaleimide I (bisindolylmaleimide) enhanced the SP-induced Cl(-) currents. However, bisindolylmaleimide abolished the inhibitory effects on SPR of the volatile anesthetics examined and of ethanol. These results demonstrate that halothane, isoflurane, enflurane, diethyl ether, and ethanol inhibit the function of SPR and suggest that activation of protein kinase C is involved in the mechanism of action of anesthetics and ethanol on the inhibitory effects of SPR. IMPLICATIONS: We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on substance P receptor (SPR) expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the anesthetics and ethanol inhibited SPR function, and the protein kinase C (PKC) inhibitor abolished these inhibitions. These results suggest that anesthetics and ethanol inhibit SPR function via PKC. PMID- 11772806 TI - The repolarizing effects of volatile anesthetics on porcine tracheal and bronchial smooth muscle cells. AB - This study was conducted to determine the effects of volatile anesthetics (potent bronchodilators) on membrane potentials in porcine tracheal and bronchial smooth muscle cells. We used a current-clamp technique to examine the effects of the volatile anesthetics isoflurane (1.5 minimum alveolar anesthetic concentration [MAC]) and sevoflurane (1.5 MAC) on membrane potentials of porcine tracheal and bronchial (third- to fifth-generation) smooth muscle cells depolarized by a muscarinic agonist, carbachol (1 microM). The effects of volatile anesthetics on muscarinic receptor binding affinity were also investigated by using a radiolabeled receptor assay technique. The volatile anesthetics isoflurane and sevoflurane induced significant repolarization of the depolarized cell membranes in the trachea (from -19.8 to -23.6 mV and to -24.8 mV, respectively) and bronchus (from -24.7 to -29.3 mV and -30.4 mV, respectively) without affecting carbachol binding affinity to the muscarinic receptor. The repolarizing effect was abolished by a Ca(2+)-activated Cl(-) channel blocker, niflumic acid. These results indicate that volatile anesthetic-induced repolarization of airway smooth muscle cell membranes might be caused by a change in Ca(2+)-activated Cl(-) channel activity and that the different repolarized effects of the volatile anesthetics could in part contribute to the different effects of volatile anesthetics on tracheal and bronchial smooth muscle contractions. IMPLICATIONS: By use of a current-clamp technique, the volatile anesthetics isoflurane and sevoflurane repolarized porcine airway smooth muscle cell membranes depolarized by a muscarinic agonist. This effect might be caused mainly by change in Ca(2+) activated Cl(-) channel activity, not in K(+) channel activity. PMID- 11772807 TI - Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model. AB - The effects of anesthesia on ischemia-reperfusion injury are of considerable scientific and clinical interest. We examined the effects of propofol (known to possess antioxidant activity) and halothane (devoid of antioxidant activity in vitro) on tissue and red blood cell (RBC) antioxidant capacity. Adult male Wistar rats were anesthetized with halothane 0.5%-1.0% (n = 7), propofol 500 microg x kg(-1) x min(-1) with halothane 0.25%-0.5% (small-dose propofol; n = 9), or propofol 2000 microg x kg(-1) x min(-1) (large-dose propofol; n = 8) for 45 min. Blood and tissue samples of liver, kidney, heart, and lung were then harvested for in vitro exposure to a peroxidizing agent. Red cell malondialdehyde and tissue thiobarbituric acid reactive substances were determined spectrophotometrically. Antioxidant capacities of blood and tissues in the Large Dose Propofol group, and of blood and all tissues except lung in the Small-Dose Propofol group, were increased significantly compared with halothane (P < 0.003). The increases in tissue antioxidant capacities varied in their magnitude: RBC > liver > kidney > heart > lung. There was a high correlation between changes in RBC susceptibility to oxidative damage and corresponding changes in tissues. These findings demonstrate that large-dose propofol significantly enhances tissue antioxidant capacity, and RBC antioxidant capacity can serve as a functional measure of tissue activity, in vivo. IMPLICATIONS: We designed this study to investigate the antioxidant effects of propofol in various tissues in a rat model. Pretreatment of animals with propofol led to a reduction in the susceptibility to an in vitro oxidative stress of five different tissues investigated, demonstrating the drug's ability to limit oxidative injury. This may have future application in limiting organ dysfunction after periods of tissue ischemia (which results in oxidative damage). PMID- 11772808 TI - Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans. AB - Opioids, including fentanyl, are often administered to patients who may be at risk for the consequences of impaired immune function. We performed a clinical study to test the effects of the synthetic opioid fentanyl on human immune function. Participants received an IV fentanyl initial dose of 3 microg/kg followed by a 2-h IV infusion of 1.2 microg x kg(-1) x h(-1). Peripheral blood was drawn before and after fentanyl administration to test for neutrophil phagocytic function, neutrophil antibody-dependent cell cytotoxicity, natural killer cell cytotoxicity, percentage of lymphocyte populations, T-lymphocyte proliferative response, and in vivo antibody response to a pneumococcal vaccine inoculation given at the end of the fentanyl infusion. Fentanyl exposure under the conditions of this study caused a rapid and significant increase in natural killer cell cytotoxicity, which was coincident with an increase in the percentage of CD16(+) and CD8(+) cells in peripheral blood. Fentanyl did not significantly affect any of the other immune measurements. IMPLICATIONS: Many previous studies have suggested that opioid drugs can impair immune resistance in patients who may be at risk for infection. This study suggests that the opioid fentanyl, when given to healthy humans without coexisting diseases, does not suppress immune resistance. On the basis of these results, the use of fentanyl should not be restricted because of concerns that it may suppress immune function. PMID- 11772809 TI - The clinical efficacy and pharmacokinetics of intraperitoneal ropivacaine for laparoscopic cholecystectomy. AB - Postoperative pain after laparoscopic surgery is less than after laparotomy, and patients may benefit from an intraperitoneal injection of local anesthetic. Thirty-seven ASA physical status I or II patients received in double-blinded fashion 20 mL of 0.9% saline solution (placebo), ropivacaine 0.25% (Rop 0.25%), or ropivacaine 0.75% (Rop 0.75%) immediately after trocar placement and at the end of surgery. We measured pain and morphine consumption until 20 h after surgery. Plasma ropivacaine concentrations were measured. The three groups were comparable for shoulder pain, parietal pain, and incidence of side effects. Visceral pain at rest, during cough, and on movement and total consumption of morphine were significantly smaller in Groups Rop 0.25% and Rop 0.75% when compared with Placebo. Although no adverse effect occurred in any patient, the largest dose led to large plasma concentrations of ropivacaine (2.93 +/- 2.46 microg/mL and 3.76 +/- 3.01 microg/mL after the first and second injection, respectively). We conclude that intraperitoneal administration of ropivacaine before and after surgery significantly decreases postoperative pain. Because the smaller dosage (2 x 50 mg) provided similar analgesia and was associated with significantly smaller plasma concentrations than the larger dosage (2 x 150 mg), this smaller dosage seems more appropriate. IMPLICATIONS: Intraperitoneal ropivacaine 100 mg injected during laparoscopic cholecystectomy significantly decreased postoperative pain when compared with injection of intraperitoneal placebo. At this dose, plasma concentrations remained in the nontoxic range, PMID- 11772810 TI - Dolasetron for preventing postanesthetic shivering. AB - We designed this study to assess the efficacy of dolasetron compared with clonidine and placebo in prophylaxis of postanesthetic shivering. We included 90 patients undergoing elective abdominal or urologic surgery. The patients were randomly assigned to one three groups (each group n = 30) using a double-blinded study protocol: Group A received 12.5 mg dolasetron, Group B 3 microg/kg clonidine, and Group C saline 0.9% as placebo. The medication was given after the induction of anesthesia. Postanesthetic shivering was judged by using a five point scale. In the Clonidine group, 86.6% showed no shivering, whereas in the Dolasetron and Placebo groups, only 63.3% and 66.6%, respectively, were symptom free. Only clonidine, but not dolasetron, significantly reduced the incidence and the severity of shivering. We conclude that clonidine is effective in preventing shivering when given before surgery, whereas dolasetron, at the dose used, is not effective. IMPLICATIONS: Shivering, an irregular muscular fasciculation lasting longer than 15 s, is a common complication secondary to general anesthesia. We compared dolasetron with clonidine (an established antishivering drug) in the prevention of postanesthetic shivering. Dolasetron 12.5 mg was not effective. PMID- 11772811 TI - Esmolol and anesthetic requirement for loss of responsiveness during propofol anesthesia. AB - The administration of esmolol decreases the propofol blood concentration, preventing movement after skin incision during propofol/morphine/nitrous oxide anesthesia. However, interaction with esmolol has not been tested when propofol is infused alone. Accordingly, we tested the hypothesis that esmolol decreases the propofol blood concentration, preventing response to command (CP50-awake) when propofol is infused alone in healthy patients presenting for minor surgery. With approval and consent, we studied 30 healthy patients, who were randomized to esmolol bolus (1 mg/kg) and then infusion (250 microg x kg(-1) x min(-1)) or placebo. Five minutes later, a target-controlled infusion of propofol was commenced. Ten minutes later, responsiveness was assessed by a blinded observer. Oxygen saturation, heart rate, and noninvasive arterial blood pressure were recorded every 2 min. Arterial blood samples were taken at 5 and 10 min of propofol infusion for propofol assay. Results were analyzed with a generalized linear regression model: P <0.05 was considered statistically significant. The probability of response to command decreased with increasing propofol blood concentration (CP50-awake = 3.42 microg/mL). Esmolol did not alter the relative risk of response to command. We conclude that the previously observed effect of esmolol on propofol CP50 was not caused by an interaction between these two drugs. IMPLICATIONS: There is no evidence to suggest that esmolol, an ultra-short acting cardioselective beta-blocker, affects anesthetic requirement for loss of responsiveness during propofol anesthesia. PMID- 11772812 TI - Vecuronium directly inhibits hypoxic neurotransmission of the rat carotid body. AB - Previous studies have suggested that partial neuromuscular blockade by vecuronium may inhibit the chemoreceptor neural response to hypoxia. Because acetylcholine and its receptors are critically involved in the hypoxic neurotransmission of the carotid body, we examined whether vecuronium interferes with nicotinic processes in the carotid body and inhibits the chemoreceptor neural response to hypoxia. The carotid body was harvested from anesthetized adult Wister rats. Carotid sinus nerve activity (CSNA) was recorded in vitro, whereas the carotid body was perfused with Krebs solutions equilibrated with 5% CO(2)/air or 5% CO(2)/N(2). Vecuronium (0.1, 0.5, and 5 microM) was administered via perfusion. Hypoxic perfusion increased CSNA and the response remained stable for two hours. With vecuronium 0.5 and 5 microM, the increase in CSNA (DeltaCSNA) in response to hypoxia was significantly attenuated. The inhibitory effect of vecuronium was dose-related. Acetylcholine and nicotine increased CSNA, and the values of DeltaCSNA were significantly attenuated by vecuronium. These results indicate that vecuronium directly inhibits the carotid body neural response to hypoxia, possibly because of the inhibition of neuronal nicotinic receptors in the carotid body. IMPLICATIONS: We investigated the effect of vecuronium on the chemoreceptor response to hypoxia with perfused rat carotid bodies. The results indicate that vecuronium significantly reduces carotid body neural responses to hypoxia, acetylcholine, and nicotine by inhibiting neuronal nicotinic receptors in the carotid body. PMID- 11772813 TI - Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium. AB - IMPLICATIONS: We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function. PMID- 11772814 TI - Bispectral index values and spectral edge frequency at different stages of physiologic sleep. AB - Bispectral index (BIS) and spectral edge frequency (SEF) are used as measures of depth of anesthesia and sedation. We tested whether these signals could predict physiologic sleep stages, by taking processed electroencephalogram measurements and recording full polysomnography through a night's sleep in 10 subjects being investigated for mild sleep apnea/hypopnea syndrome. Computerized polysomnograph signals were analyzed manually according to standard criteria, classifying each 30-s epoch as a specific sleep stage. The BIS and SEF values were taken at the end of each period of sleep when the same stage had lasted for at least 2 min. Before sleep, median values for BIS were 97 +/- 12.1 and for SEF 23 +/- 4.2 Hz. After sleep initiation, the median BIS values for arousal, light, slow wave, and rapid eye movement sleep were 67 +/- 20.2, 50 +/- 16.5, 42 +/- 11.2, and 48 +/- 7.1, respectively, and the median SEF values were 20 +/- 4.7, 15 +/- 3.6, 10 +/- 2.6, and 19 +/- 4.1 Hz, respectively. Although both BIS and SEF decreased with increasing sleep depth, the distribution of values at each sleep depth was considerable, with overlap between each sleep stage. Neither BIS nor SEF reliably indicated conventionally determined sleep stages. In addition, the response of the BIS was slow and patients could arouse with low BIS values, which then took some time to increase. IMPLICATIONS: Although computer processing of the electroencephalogram can provide an adequate index of depth of anesthesia, the same processing cannot reliably convey depth of natural sleep. At each sleep stage, the output signal has a wide range of possible values. PMID- 11772815 TI - Postoperative analgesia: economics, resource use, and patient satisfaction in an urban teaching hospital. AB - We sought to describe the economic and humanistic burden after total abdominal hysterectomy (TAH), total hip replacement (THR), or total knee replacement (TKR) surgery. Resource use and costs were estimated from the hospital perspective. The mean worst pain severity was 8.9, 8.1, and 7.6 on a 0- to 10-point scale after TAH, THR, and TKR, respectively. Postoperative pain was worst on postoperative day 1 after TAH or THR, and on postoperative day 2 after TKR. Analgesic medications relieved from 60% to nearly 78% of postoperative pain, but participants re- ported moderate-to-high levels of interference with general activity, walking ability, and sleep because of postoperative pain. Most costs were attributed to the hospital admission and operating room. The average length of hospitalization was 2.8 days after TAH, and 3.9 days after THR or TKR. This study provides insight into patients' experience with pain after common surgeries, perioperative costs, and medical resource use. IMPLICATIONS: Despite impressive relief with analgesics, postoperative pain interferes with patients' ability to sleep, walk, and participate in other activities. Medications used postoperatively account for a small portion of total costs. Satisfaction ratings alone are a poor indicator of pain control. These data can be used to help improve pain relief. PMID- 11772816 TI - Calculating a potential increase in hospital margin for elective surgery by changing operating room time allocations or increasing nursing staffing to permit completion of more cases: a case study. AB - Administrators routinely seek to increase contribution margin (revenue minus variable costs) to better cover fixed costs, provide indigent care, and meet other community service responsibilities. Hospitals with high operating room (OR) utilizations can allocate OR time for elective surgery to surgeons based partly on their contribution margins per hour of OR time. This applies particularly when OR caseload is limited by nursing recruitment. From a hospital's annual accounting data for elective cases, we calculated the following for each surgeon's patients: variable costs for the entire hospitalization or outpatient visit, revenues, hours of OR time, hours of regular ward time, and hours of intensive care unit (ICU) time. The contribution margin per hour of OR time varied more than 1000% among surgeons. Linear programming showed that reallocating OR time among surgeons could increase the overall hospital contribution margin for elective surgery by 7.1%. This was not achieved simply by taking OR time from surgeons with the smallest contribution margins per OR hour and giving it to the surgeons with the largest contribution margins per OR hour because different surgeons used differing amounts of hospital ward and ICU time. We conclude that to achieve substantive improvement in a hospital's perioperative financial performance despite restrictions on available OR, hospital ward, or ICU time, contribution margin per OR hour should be considered (perhaps along with OR utilization) when OR time is allocated. IMPLICATIONS: For hospitals where elective surgery caseload is limited by nursing recruitment, to increase one surgeon's operating room time either another surgeon's time must be decreased, nurses need to be paid a premium for working longer hours, or higher-priced "traveling" nurses can be contracted. Linear programming was performed using Microsoft Excel to estimate the effect of each of these interventions on hospital contribution margin. PMID- 11772817 TI - Operating room managers' use of integer programming for assigning block time to surgical groups: a case study. AB - A common problem at hospitals with fixed amounts of available operating room (OR) time (i.e., "block time") is determining an equitable method of distributing time to surgical groups. Typically, facilities determine a surgical group's share of available block time using formulas based on OR utilization, contribution margin, or some other performance metric. Once each group's share of time has been calculated, a method must be found for fitting each group's allocated OR time into the surgical master schedule. This involves assigning specific ORs on specific days of the week to specific surgical groups, usually with the objective of ensuring that the time assigned to each group is close to its target share. Unfortunately, the target allocated to a group is rarely expressible as a multiple of whole blocks. In this paper, we describe a hospital's experience using the mathematical technique of integer programming to solve the problem of developing a consistent schedule that minimizes the shortfall between each group's target and actual assignment of OR time. Schedule accuracy, the sum over all surgical groups of shortfalls divided by the total time available on the schedule, was 99.7% (SD 0.1%, n = 11). Simulations show the algorithm's accuracy can exceed 97% with > or =4 ORs. The method is a systematic and successful way to assign OR blocks to surgeons. IMPLICATIONS: At hospitals with a fixed budget of operating room (OR) time, integer programming can be used by OR managers to decide which surgical group is to be allocated which OR on which day(s) of the week. In this case study, we describe the successful application of integer programming to this task, and discuss the applicability of the results to other hospitals. PMID- 11772818 TI - The use of a human patient simulator in the evaluation of and development of a remedial prescription for an anesthesiologist with lapsed medical skills. AB - The New York State Society of Anesthesiologists' Committee on Continuing Medical Education and Remediation has been charged by the Office of Professional Medical Conduct of the New York State Department of Health to develop a remediation program for individuals ordered into retraining. We describe the development of an anesthesiology-specific evaluation to identify areas of deficiency to both determine a candidate's suitability, as well as to facilitate the creation of an appropriate prescription for retraining. A human patient simulator was used to aid in the gathering of information during the evaluation process. Specifically, the use of simulation allowed the exploration of a candidate's preparation, approach to clinical situations, technical abilities, response to clinical problems, ability to problem solve, and accuracy of medical record keeping. Human patient simulation should be considered a valuable tool in the process of evaluating physicians with lapsed medical skills. PMID- 11772819 TI - Human error: the persisting risk of blood transfusion: a report of five cases. AB - It is common experience that virus transmission, particularly transmission of the human immunodeficiency virus (HIV), is a principal concern of patients and physicians regarding blood transfusion (1). Many physicians are probably unaware that transfusion-transmitted HIV infection is approximately 50 to 100 times less likely to occur than transfusion error (2-4). This misconception may have been encouraged by the scarcity of reports on transfusion error relative to the tremendous public attention focused on HIV infection. We present five cases illustrating how anesthesiologists, intensivists, and emergency physicians are particularly vulnerable to the risk of administering blood to the wrong recipient. All five cases were collected during a 4-yr period. Transfused units of packed red cells totaled approximately 50,000 U during this period in our department. IMPLICATIONS: Human error leading to the transfusion of blood to an unintended recipient is a major source of transfusion-related fatalities. We report five cases that highlight some specific areas in which transfusion error is likely to occur. PMID- 11772820 TI - Physiologic characteristics of cold perfluorocarbon-induced hypothermia during partial liquid ventilation in normal rabbits. AB - Because perfluorocarbon (PFC) liquid contacts closely with the alveolar capillaries during partial liquid ventilation (PLV), PLV with cold PFC may be used for the induction of hypothermia. Twenty rabbits were randomized to PFC induced hypothermia (PH) (n = 7; core temperature 35 degrees +/- 1 degrees C), surface hypothermia (SH) (n = 7; 35 degrees +/- 1 degrees C), or normothermia (n = 6; 39 degrees +/- 1 degrees C). We induced PH by repeated in situ exchanges of 0 degrees C perfluorodecalin during PLV. At the establishment (0 min) of hypothermia in the PH group, oxygen consumption (P = 0.04) and oxygen extraction ratio (P = 0.01) decreased from normothermic condition. Metabolic (oxygen consumption, oxygen extraction ratio, serum lactate level) and hemodynamic variables (heart rate, blood pressure, cardiac output, pulmonary artery pressure) of the PH group were not different from those of the SH group at 0, 30, 60, 90, and 120 min of hypothermia. The difference in temperature between the pulmonary artery and rectum during the hypothermic period was smaller in the PH group compared with the SH group (P = 0.033). In conclusion, hypothermia may be induced during PLV by using cold PFC. This "pulmonary method" of cooling was comparable to a systemic method of cooling with regard to a few important physiologic variables, while maintaining a narrower interorgan temperature difference. IMPLICATIONS: The induction of moderate hypothermia was feasible in rabbits by administrating cold perfluorocarbon liquid into the lung. Physiologic changes induced by this pulmonary cooling were comparable to those induced by systemic cooling. Our method may be regarded as a methodological advance in the field of therapeutic hypothermia. PMID- 11772821 TI - Remifentanil provides hemodynamic stability and faster awakening time in transsphenoidal surgery. AB - In this prospective study, we evaluated the effects of remifentanil in ASA I-II patients undergoing transsphenoidal surgery. After the induction of anesthesia, patients were randomly allocated to the Isoflurane (n = 22, 60% nitrous oxide, isoflurane up to 2% end-tidal) or Remifentanil group (n = 21, 60% nitrous oxide, 0.5% end-tidal isoflurane, remifentanil up to 2 microg x kg(-1) x min(-1)). If mean arterial pressure (MAP) increased >80 mm Hg during maximal dosage of isoflurane or remifentanil, labetalol was administered. At the end of anesthesia, extubation and awakening times, respiratory rate, SpO(2), MAP, heart rate, and adverse effects were recorded. Hemodynamics and bleeding (minimal, mild, moderate, severe) were not different between groups. Bleeding grade increased with MAP >80 mm Hg (P < 0.001). Labetalol was administered to 20 patients in the Isoflurane group, and 10 patients in the Remifentanil group (P < 0.01). The dose of labetalol was larger in the Isoflurane group (1.0 +/- 0.6 versus 0.5 +/- 0.7 mg/kg, P < 0.05). Time to extubation did not differ, whereas time to follow commands was shorter in Remifentanil patients (16 +/- 8 versus 10 +/- 2 min, P < 0.01). No adverse effects occurred in the early postoperative period. IMPLICATIONS: In patients undergoing transsphenoidal surgery, balanced anesthesia with remifentanil (0.22 +/- 0.17 microg x kg(-1) x min(-1)) provides faster awakening time, as compared with large-dose volatile-based anesthesia, without the risk of postoperative opioid respiratory depression. PMID- 11772822 TI - The influence of nicardipine-, nitroglycerin-, and prostaglandin E(1)-induced hypotension on cerebral pressure autoregulation in adult patients during propofol fentanyl anesthesia. AB - We investigated the influence of drug-induced hypotension at a mean arterial pressure (MAP) of 60-70 mm Hg on cerebral pressure autoregulation in 45 adult patients during propofol-fentanyl anesthesia. Time-averaged mean blood flow velocity in the right middle cerebral artery (Vmca) was continuously measured at a PaCO(2) of 39-40 mm Hg by using transcranial Doppler ultrasonography. Hypotension was induced and maintained with a continuous infusion of nicardipine, nitroglycerin, or prostaglandin E(1). Cerebral autoregulation was tested by a slow continuous infusion of phenylephrine to induce an increase in MAP of 20-30 mm Hg. From the simultaneously recorded data of Vmca and MAP, cerebral vascular resistance (CVR) was calculated as MAP/Vmca. Furthermore, the index of autoregulation (IOR) was calculated as DeltaCVR/DeltaMAP, where DeltaCVR = change in CVR and DeltaMAP = change in MAP. The test was performed twice for each condition on each patient: baseline and hypotension. The IOR during baseline was similar among the groups. During nitroglycerin- and prostaglandin E(1)-induced hypotension, IOR was not different from baseline. In contrast, during nicardipine induced hypotension, IOR significantly decreased compared with baseline (0.37 +/- 0.08 versus 0.83 +/- 0.07, P < 0.01). In conclusion, nicardipine, but not nitroglycerin or prostaglandin E(1), significantly attenuates cerebral pressure autoregulation during propofol-fentanyl anesthesia. IMPLICATIONS: Vasodilators may influence cerebral autoregulation by changing cerebral vascular tone. Nicardipine, but not nitroglycerin or prostaglandin E(1), attenuated cerebral pressure autoregulation in normal adult patients during propofol-fentanyl anesthesia. PMID- 11772824 TI - Ropivacaine 0.075% and bupivacaine 0.075% with fentanyl 2 microg/mL are equivalent for labor epidural analgesia. AB - Fifty percent effective dose estimates for ropivacaine and bupivacaine suggest that ropivacaine is 40% less potent than bupivacaine to initiate labor analgesia. At clinically used concentrations, however, the drugs seem indistinguishable for initiating and maintaining labor analgesia. We designed this study to evaluate a concentration near the reported 50% effective dose values for ropivacaine and bupivacaine in an attempt to detect differences between the drugs during routine clinical use. Fifty-nine nulliparous women in labor were randomized to receive 0.075% ropivacaine or bupivacaine, each with fentanyl 2 microg/mL. After epidural placement and the administration of a lidocaine/epinephrine test dose, 20 mL of study solution was administered and a patient-controlled epidural infusion was initiated with the following settings: 6 mL/h basal rate, 5 mL bolus, 10 min lockout, and 30 mL/h limit. Breakthrough pain was treated with 10-mL boluses of study solution. By using a study design to detect a 40% difference in hourly drug use between groups, we found no statistically significant differences in the amount of local anesthetic used, verbal pain scores, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction. We conclude that 0.075% ropivacaine and bupivacaine, with fentanyl, are equally effective for labor analgesia using the patient-controlled epidural analgesia technique. IMPLICATIONS: At small concentrations, ropivacaine and bupivacaine when combined with fentanyl are equally effective for labor analgesia. Patients self-administered similar volumes of 0.075% ropivacaine or bupivacaine solutions containing fentanyl (2 microg/mL) suggesting that at this concentration, and with the addition of fentanyl, ropivacaine and bupivacaine can be used interchangeably. PMID- 11772823 TI - The role of K(+) channels on the inhibitor effect of sevoflurane in pregnant rat myometrium. AB - Volatile anesthetics and K(+) channel openers inhibit spontaneous contractions in myometrial smooth muscle. Volatile anesthetics modulate K(+) channel activity. We investigated the role of two K(+) channel blockers on the effect of sevoflurane in pregnant rat myometrium. Term pregnant rat uteri were excised, and cross sectional myometrial strips were mounted for isometric force recording. Sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner. The maximal inhibition measured in amplitude and frequency of spontaneous myometrial contractions with sevoflurane (at 3 minimum alveolar anesthetic concentration) was 44.32% and 33.32% of control contractions, respectively. Tetraethylammonium (TEA) and glibenclamide, K(+) channel blockers, increased spontaneous myometrial contractions in a concentration-dependent manner. Sevoflurane responses were repeated at concentrations with no effect on spontaneous contractility of TEA, a Ca(2+)-activated K(+) channel blocker, and glibenclamide, an adenosine triphosphate-sensitive K(+) channel blocker, in myometrial strips. TEA (3.10(-4) M) caused a significant reduction in sevoflurane-induced inhibitor responses, but glibenclamide (10(-6) M) did not. Sevoflurane-induced maximal inhibition (at 3 minimum alveolar anesthetic concentration) on amplitude and frequency of spontaneous myometrial contractions in the presence of TEA (3.10(-4) M) was 31.85% and 22.33% of control contractions, respectively (P < 0.05). These results suggest that the in vitroapplication of sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in pregnant rats in a concentration-dependent manner. Such inhibition was reduced by TEA. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by TEA. IMPLICATIONS: In this study, we found that sevoflurane causes significantly decreased myometrial contractile activity in pregnant rats. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by tetraethylammonium. PMID- 11772825 TI - Colostrum morphine concentrations during postcesarean intravenous patient controlled analgesia. AB - Patient-controlled analgesia (PCA) with morphine is a convenient method for providing postoperative analgesia. Despite the fact that it is used after cesarean delivery, data on transfer of morphine and of its active metabolite morphine-6 glucuronide (M6G) into maternal milk are scarce. It is not known whether breast-feeding during PCA with morphine has neonatal implications. We sought to measure morphine and M6G concentrations in colostrum during postpartum IV PCA and evaluate the potential for drug intake by neonates being breast-fed by these mothers. Seven informed and consenting mothers, given IV PCA with morphine, were investigated. Plasma and milk samples were obtained at titration, and at 12, 24, 36, and 48 h. Morphine and M6G were measured by high-performance liquid chromatography. In plasma, morphine concentrations ranged from <1 to 274 ng/mL, M6G ranged from <5 to 974 ng/mL. In milk, opioids were found in only 3 patients in whom morphine concentrations ranged from <1 to 48 ng/mL and M6G from <5 to 1084 ng/mL. The milk-to-plasma ratio was always <1 for morphine. In conclusion, we observed very small morphine and M6G concentrations in colostrum during PCA with morphine. Under these conditions, the amounts of drug likely to be transferred to the breast-fed neonate are negligible. IMPLICATIONS: Colostrum concentrations of morphine and its active metabolite morphine-6 glucuronide were measured in mothers receiving patient-controlled analgesia with morphine after cesarean delivery. The concentrations were found to be very small, thus supporting the safety of breast-feeding in mothers receiving IV patient controlled analgesia with morphine. PMID- 11772826 TI - Hyperbaric spinal levobupivacaine: a comparison to racemic bupivacaine in volunteers. AB - Levobupivacaine is the isolated S-enantiomer of bupivacaine and may be a favorable alternative to spinal bupivacaine. However, its clinical efficacy relative to bupivacaine and its dose-response characteristics, in spinal anesthesia, must first be known. This double-blinded, randomized, cross-over study was designed to compare the clinical efficacy of hyperbaric levobupivacaine and bupivacaine for spinal anesthesia. Eighteen healthy volunteers were randomized into three equal groups to receive two spinal anesthetics, one with bupivacaine and the other with levobupivacaine, of equal-milligram doses (4, 8, or 12 mg). We assessed blockade quality and duration with pinprick, transcutaneous electrical stimulation, thigh tourniquet, abdominal and quadriceps muscle strength, modified Bromage scale, and time until achievement of discharge criteria. Sensory and motor block were similar between the same doses of levobupivacaine and bupivacaine (P > 0.56 to 0.86). For example, in the 12-mg groups of levobupivacaine versus bupivacaine, mean duration of tolerance to transcutaneous electrical stimulation at T12 was 100 min for both. The duration of motor block at the quadriceps was 71 versus 73 min, and time until achievement of discharge criteria was 164 min for both. Hyperbaric spinal levobupivacaine has equivalent clinical efficacy to racemic bupivacaine for spinal anesthesia in doses from 4 to 12 mg. IMPLICATIONS: Hyperbaric spinal levobupivacaine has equivalent clinical efficacy to hyperbaric spinal bupivacaine over the 4-12-mg ranges. PMID- 11772827 TI - Levobupivacaine versus racemic bupivacaine for spinal anesthesia. AB - Levobupivacaine is the pure S(-)-enantiomer of racemic bupivacaine but is less toxic to the heart and central nervous system. Although it has recently been introduced for routine obstetric and nonobstetric epidural anesthesia, comparative clinical studies on its intrathecal administration are not available. We therefore performed this prospective randomized double-blinded study to evaluate the anesthetic potencies and hemodynamics of intrathecal levobupivacaine compared with racemic bupivacaine. Eighty patients undergoing elective hip replacement received either 3.5 mL levobupivacaine 0.5% isobaric or 3.5 mL bupivacaine 0.5% isobaric. Sensory blockade was verified with the pinprick test; motor blockade was documented by using a modified Bromage score. Hemodynamic variables (e.g., blood pressure, heart rate, pulse oximetry) were also recorded. Intergroup differences between levobupivacaine and bupivacaine were insignificant both with regard to the onset time and the duration of sensory and motor blockade (11 +/- 6 versus 13 +/- 8 min; 10 +/- 7 versus 9 +/- 7 min; 228 +/- 77 versus 237 +/- 88 min; 280 +/- 84 versus 284 +/- 80 min). Both groups showed slight reductions in heart rate and mean arterial pressure, but there was no intergroup difference in hemodynamics. We conclude that intrathecal levobupivacaine is equal in efficacy to, but less toxic than, racemic bupivacaine. IMPLICATIONS: Levobupivacaine, the pure S(-)-enantiomer of racemic bupivacaine is an equally effective local anesthetic for spinal anesthesia compared with racemic bupivacaine. PMID- 11772828 TI - Suprascapular nerve block for ipsilateral shoulder pain after thoracotomy with thoracic epidural analgesia: a double-blind comparison of 0.5% bupivacaine and 0.9% saline. AB - Despite receiving thoracic epidural analgesia, severe ipsilateral shoulder pain is common in patients after thoracotomy. We recruited 44 patients into a double blinded randomized placebo-controlled study to investigate whether suprascapular nerve block would treat postthoracotomy shoulder pain effectively. All patients received a standard anesthetic with a midthoracic epidural. Thirty patients who experienced shoulder pain within 2 h of surgery were randomly assigned to receive a suprascapular nerve block with either 10 mL of 0.5% bupivacaine or 10 mL of 0.9% saline. Shoulder pain was assessed before nerve blockade, at 30 min, and then hourly for 6 h after the block using a visual analog scale (VAS) and a 5 point verbal ranking score (VRS). The incidence of shoulder pain before nerve block was 78%. There was no significant decrease in either VAS or VRS in the Bupivacaine group. These results suggest that this pain is unlikely to originate in the shoulder and lead us to question the role of a somatic afferent in referred visceral pain. We conclude that suprascapular nerve block does not treat ipsilateral shoulder pain after thoracotomy in patients with an effective thoracic epidural. IMPLICATIONS: This randomized, double-blinded, placebo controlled trial showed that suprascapular nerve block does not treat the severe ipsilateral shoulder pain that patients experience after thoracotomy. This has implications for established theories of referred pain and indicates that this pain is unlikely to originate in the shoulder. PMID- 11772829 TI - Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts. AB - Lidocaine, phenytoin, and bupivacaine are sodium channel blockers. Lidocaine displaces bupivacaine from its receptor on the sodium channel. However, lidocaine does not seem to decrease bupivacaine toxicity. Phenytoin also has been used to treat bupivacaine cardiotoxicity. To test the hypothesis that lidocaine or phenytoin might be used for the treatment of bupivacaine overdose, we compared the effects of bupivacaine on intraventricular conduction in the isolated heart of rabbits with bupivacaine and with either phenytoin or lidocaine added to bupivacaine. Twenty-four rabbit hearts were retrogradely perfused in a nonrecirculating Langendorff apparatus. The duration of QRS was measured without any drug and 10 min after infusion of 3 microM bupivacaine. Saline (control group) or increasing concentrations of either lidocaine or phenytoin was then added by 10-min-step increments. QRS duration was measured for each concentration at the end of a 10-min step. It was also determined 10 min after discontinuation of bupivacaine and after a period of washout for all drugs. QRS duration was significantly increased by adding phenytoin or lidocaine to bupivacaine. These drugs should not be used to treat the manifestations of bupivacaine toxicity. IMPLICATIONS: The effects of lidocaine and phenytoin on bupivacaine-related increases in cardiac conduction time have been studied in an isolated heart preparation. Both drugs increased the QRS widening induced by bupivacaine. We conclude that none of these drugs should be used for treating bupivacaine intoxication. PMID- 11772830 TI - Acute experimental allergic encephalomyelitis increases lumbar spinal cord incorporation of epidurally administered [(3)H]-D-mannitol and [(14)C]-carboxyl inulin in rabbits. AB - We sought to determine whether acute experimental allergic encephalomyelitis (EAE) alters the incorporation of epidurally administered [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin into the lumbar spinal cord in rabbits. Acute EAE is an experimental model for demyelinating spinal cord diseases such as multiple sclerosis. It was induced in rabbits by footpad inoculation with rabbit spinal cord homogenate, resulting in hind limb paresis or paralysis. Animals were classified into four study groups: Control, Paraparesis, 1-Day Paraplegia, and 5 Day Paraplegia. Ten microCi each of [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin were administered epidurally for 90 min. After infusion, animals were perfused with saline. The lumbar cord was dissected and divided into 11 segments. Compared with other groups, animals in the 5-Day Paraplegia group had greater incorporation of [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin in lumbar segment 8, corresponding to the location of the epidural catheter tip. Compared with the Control group, EAE animals had increased [(3)H]-D-mannitol incorporation in various lumbar segments. Increases in the spinal cord incorporation of epidural drugs with EAE suggest that demyelination may render the spinal cord susceptible to larger amounts of substances administered in the epidural space. These findings may have implications regarding neurotoxicity in association with demyelinating spinal cord disease. IMPLICATIONS: Acute experimental allergic encephalomyelitis, a disease model for multiple sclerosis, increased spinal cord incorporation of radioactive drugs administered in the epidural space. We conclude that demyelinating disease processes may expose the spinal cord to larger amounts of substances administered neuraxially. PMID- 11772831 TI - Transient neurological symptoms after subarachnoid meperidine. AB - IMPLICATIONS: The syndrome of transient neurological symptoms (TNS) after subarachnoid use of local anesthetics, particularly lidocaine, has been well described. This syndrome has not been reported with the subarachnoid use of opioids. This case report describes TNS that occurred after administration of subarachnoid meperidine, an opioid with local anesthetic properties. PMID- 11772832 TI - What are the most important risk factors for a patient's developing intraoperative hypothermia? AB - Anesthesiologists attempt to maintain perioperative normothermia for surgical patients. We surveyed clinical anesthesiologists and physician researchers and asked them to prioritize risk factors for a patient to develop intraoperative hypothermia. The questionnaire included 41 factors associated with changes in patient temperature identified during a computerized literature search. We asked respondents to estimate the relative importance of each risk factor on a 10-point scale. The survey was mailed to two groups: 1) 180 anesthesiologists (n = 84 respondents) randomly selected from the 1999 American Society of Anesthesiologists Members Directory and to 2) 24 physician researchers (n = 12 respondents) in thermoregulation. Researchers rated the following to be the most important risk factors for hypothermia (in sequence): neonates, a low ambient operating room temperature, burn injuries, general anesthesia with neuraxial anesthesia, geriatric patients, low temperature of the patient before induction, a thin body type, and large blood loss. The results for the clinician group were similar, because the median differences between the groups' results were two or fewer units for all items. The risk factors identified to be most important can now be further evaluated in clinical trials to develop a multivariate predictive tool for calculating a patient's a priori risk for developing hypothermia. IMPLICATIONS: Surveys of clinicians and physician researchers identified what they consider to be the most important risk factors for perioperative hypothermia (e.g., neonates, a low ambient operating room temperature, burn patients, and general anesthesia with neuraxial anesthesia). PMID- 11772833 TI - Thermoregulatory response to intraoperative head-down tilt. AB - Thermoregulation interacts with cardiovascular regulation within the central nervous system. We therefore evaluated the effects of head-down tilt on intraoperative thermal and cardiovascular regulation. Thirty-two patients undergoing lower-abdominal surgery were randomly assigned to the 1) supine, 2) 15 degrees -20 degrees head-down tilt, 3) leg-up, or 4) combination of leg-up and head-down tilt position. Core temperature and forearm minus fingertip skin temperature gradients (an index of peripheral vasoconstriction) were monitored for 3 h after the induction of combined general and lumbar epidural anesthesia. We also determined cardiac output and central-venous and esophageal pressures. Neither right atrial transmural pressure nor cardiac index was altered in the Head-Down Tilt group, but both increased significantly in the Leg-Up groups. The vasoconstriction threshold was reduced in both leg-up positions but was not significantly decreased by head-down tilt. Final core temperatures were 35.2 degrees C +/- 0.2 degrees C (mean +/- SEM) in the Supine group, 35.0 degrees C +/ 0.2 degrees C in the Head-Down Tilt group, 34.2 degrees C +/- 0.2 degrees C in the Leg-Up group (P < 0.05 compared with supine), and 34.3 degrees C +/- 0.2 degrees C when leg-up and head-down tilt were combined (P < 0.05 compared with supine). These results confirm that elevating the legs increases right atrial transmural pressure, reduces the vasoconstriction threshold, and aggravates intraoperative hypothermia. Surprisingly, maintaining a head-down tilt did not increase right atrial pressure. IMPLICATIONS: Intraoperative hypothermia is exaggerated when patients are maintained in the leg-up position because the vasoconstriction threshold is reduced. However, head-down tilt (Trendelenburg position) does not reduce the vasoconstriction threshold or aggravate hypothermia. The head-down tilt position thus does not require special perioperative thermal precautions or management unless the leg-up position is used simultaneously. PMID- 11772834 TI - Alkalinization of intracuff lidocaine improves endotracheal tube-induced emergence phenomena. AB - We sought to evaluate the effect of filling an endotracheal tube cuff with 40 mg lidocaine alone (Group L) or alkalinized lidocaine (Group LB) in comparison to an Air Control group (Group C) on adverse emergence phenomena in a randomized controlled study (n = 25 in each group). The incidence of sore throat was decreased for Group LB in comparison to Group L during the 24 postextubation hours. The difference between Group L and Group C remained significant in the two postextubation hours only. Plasma lidocaine levels increased when lidocaine was alkalinized (C(max) were 62.5 +/- 34.0 ng/mL and 3.2 +/- 1.0 ng/mL for Groups LB and L, respectively). Cough and restlessness before tracheal extubation were decreased in Group LB compared with Group L and in Group L compared with Group C. Nausea, postoperative vomiting, dysphonia, and hoarseness were increased after extubation in Group C compared with the liquid groups, and a better tolerance was recorded with Group LB compared with Group L. The increase of arterial blood pressure and cardiac frequencies during the extubation period was less in the liquid groups than in the control group and less in Group LB compared with Group L. We concluded that use of intracuff alkalinized lidocaine is an effective adjunct to endotracheal intubation. IMPLICATIONS: Use of 40 mg of alkalinized lidocaine, rather than lidocaine or air, to fill the endotracheal tube cuff reduces the incidence of sore throat in the postoperative period. This approach also decreases hemodynamic effects, restlessness, dysphonia, and hoarseness. PMID- 11772835 TI - Difficult endotracheal intubation as a result of penetrating cranio-facial injury by an arrow. AB - Penetrating injury of the face and airway may make endotracheal intubation difficult or impossible. We report the case of a patient who attempted to commit suicide with a crossbow. Surgery under general anesthesia was required to remove the arrow. The oral intubation route was impossible, and a fiberoptic nasal intubation under local anesthesia was performed. IMPLICATIONS: We report a case of a 42-yr-old patient who underwent surgery for a penetrating craniofacial injury caused by an arrow. Because of the median vertical trajectory of the arrow (from the chin to the frontal skull), only the right nasal approach was accessible for endotracheal intubation. Fiberoptic nasal intubation and securing the airway under local anesthesia are described. PMID- 11772836 TI - A safe anesthetic method using caudal block and ketamine for the child with congenital myotonic dystrophy. PMID- 11772837 TI - Is it ethically correct to study the Quincke spinal needle in obstetric patients? PMID- 11772838 TI - Another cause of epidural catheter breakage? PMID- 11772839 TI - Hazard with a triple-lumen catheter. PMID- 11772840 TI - Capnography and severe COPD. PMID- 11772841 TI - User-led research and evidence-based medicine. PMID- 11772842 TI - Remembering delirium. PMID- 11772843 TI - The Commission for Health Improvement (CHI) review of North Birmingham Mental Health Trust: what can we hope for from the CHI? PMID- 11772844 TI - The case against "the evidence": a different perspective on evidence-based medicine. AB - BACKGROUND: An evidenced-based approach to psychiatry is playing an increasingly prominent role in treatment decision-making for individual patients and for populations. Many doctors are now critical of the emphasis being placed on "the evidence" and concerned that clinical practice will become more constrained. AIMS: To demonstrate that evidence-based medicine is not new, sources of evidence are limited and psychosocial aspects of medicine are neglected in this process. METHOD: Some of the literature is reviewed. Ideas and arguments are synthesised into a critical commentary. RESULTS: These are considered under four headings: evidence-based medicine is not new; what evidence is acceptable; the doctor as therapist; and the emergence of a new utilitarian orthodoxy. CONCLUSIONS: It is agreed that a degree of professional consensus is necessary. However, too great an emphasis on evidence-based medicine oversimplifies the complex and interpersonal nature of clinical care. PMID- 11772845 TI - Improving the delivery and organisation of mental health services: beyond the conventional randomised controlled trial. AB - BACKGROUND: There is an ethical imperative to evaluate service and policy initiatives, such as those highlighted in the recent National Service Framework, just as there is to evaluate individual treatments. AIMS: To outline the best methods available for evaluating the delivery and organisation of mental health services. METHOD: We present a narrative methodological overview, using salient examples from mental health services research. RESULTS: Cluster randomised studies involve the random allocation of groups of clinicians, clinical teams or hospitals rather than individual patients, and produce the least biased evaluation of mental health policy, organisation or service delivery. Where randomisation is impossible or impractical (often when services or policies are already implemented), then quasi-experimental designs can be used. Such designs have both strengths and many potential flaws. CONCLUSIONS: The gold standard remains the randomised trial, but with due consideration to the unit of randomisation. Use of quasi-experimental designs can be justified in certain circumstances but should be attempted and interpreted with caution. PMID- 11772846 TI - The Maudsley long-term follow-up of child and adolescent depression: 3. Impact of comorbid conduct disorder on service use and costs in adulthood. AB - BACKGROUND: Depression in childhood or adolescence often has morbidity implications continuing into adulthood, generating needs for specialist services and support. AIMS: To estimate the patterns of service use and costs in adulthood of former patients. METHOD: Service use and other cost-related data were collected from former patients. Comparisons were made between those people with and without comorbid conduct disorder in childhood and with data for the general population. RESULTS: Data on 91 people with depression (only) and 49 with comorbid conduct disorder revealed high adulthood service utilisation rates and costs. Inpatient care and criminal justice services were used more frequently by the comorbid group and total costs were significantly higher. There were also indications of higher service use by the comorbid group than the general adult population. CONCLUSIONS: The high and enduring long-term costs associated with childhood depression and conduct disorder give further reason for early and effective intervention. PMID- 11772847 TI - State and trait abnormalities in serotonin function in major depression. AB - BACKGROUND: Neuroendocrine studies of brain serotonin (5-HT) function in depression generally show evidence of impaired 5-HT function but it is disputed whether or not this impairment resolves with clinical recovery. AIMS: To use the endocrine response to the selective 5-HT reuptake inhibitor, citalopram, to study brain 5-HT function in acute and recovered depressed subjects relative to healthy controls. METHOD: We used a double-blind, placebo-controlled design to measure the prolactin and cortisol responses to citalopram (10 mg intravenously) in patients with major depression, in unmedicated subjects recovered from depression and in healthy controls. RESULTS: The prolactin responses to citalopram were blunted similarly in both acutely depressed and recovered subjects. The cortisol responses were blunted in the acutely depressed patients but not in the recovered subjects. CONCLUSIONS: Our data support the proposal that some aspects of impaired 5-HT neurotransmission may be trait markers of vulnerability to depression. The recovery of the cortisol response to citalopram may indicate resolution of hypothalamic-pituitary-adrenal axis dysfunction. PMID- 11772848 TI - Chronic fatigue and anxiety/depression: a twin study. AB - BACKGROUND: Up to three-quarters of patients with fatigue syndromes have comorbid mood or anxiety disorders, suggesting that chronic fatigue is a forme fruste of anxiety or depressive states. AIMS: To establish whether the association of chronic fatigue with psychological distress is causal or due to a common genetic or environmental factor. METHOD: 69 monozygotic (MZ) and 31 dizygotic (DZ) female twin pairs, with only one co-twin reporting at least 6 months of fatigue, completed questions on fatigue, the General Health Questionnaire (GHQ) and a structured psychiatric interview. We examined the effects of three progressively more stringent definitions of chronic fatigue on four GHQ sub-scales. RESULTS: Fatigued MZ and DZ twins by all definitions were significantly more depressed, anxious, somatically preoccupied and socially dysfunctional than their non fatigued co-twins. Intrapair differences were similar in DZ and MZ twins, but non significant differences were observed for the somatic symptoms and anxiety/insomnia sub-scales. CONCLUSIONS: In this sample, chronic fatigue and psychological distress are strongly associated without evidence for genetic covariation, implying that the association is environmental, or due to overlapping definitions. Any genetic covariation missed is likely to involve anxiety rather than depression. PMID- 11772849 TI - Heritability of Schneider's first-rank symptoms. AB - BACKGROUND: Schneider's first-rank symptoms are given particular weight when making a diagnosis of schizophrenia, but the nuclear syndrome, characterised by one or more first-rank symptoms, has been found previously to have no heritability. AIMS: To estimate the heritability of the nuclear syndrome. METHOD: A total of 224 twin pairs (106 monozygotic, 118 same-gender dizygotic) were ascertained from the Maudsley Twin Register in London via probands with any psychosis. Lifetime-ever first-rank symptoms were rated using the OPCRIT checklist. Probandwise concordance rates were calculated for the nuclear syndrome and a heritability estimate was derived from biometric model fitting. RESULTS: Probandwise concordance rates were 13/49 (26.5%) for monozygotic and 0/45 to 2/46 (0.0-4.3%) for dizygotic pairs. The heritability estimate for the best-fitting model was 71% (95% CI 57-82). CONCLUSIONS: These results indicate that the nuclear syndrome shows substantial heritability, although this is slightly lower than that for schizophrenia as defined by the DSM and ICD systems. PMID- 11772850 TI - Region-specific changes in phospholipid metabolism in chronic, medicated schizophrenia: (31)P-MRS study at 4.0 Tesla. AB - BACKGROUND: Membrane phospholipid abnormalities in people with schizophrenia, measured with (31)P magnetic resonance spectroscopy ((31)P-MRS), have been previously reported in brain regions involved in this disorder. AIMS: In this 4.0 Tesla (31)P-MRS study of people with schizophrenia, membrane phospholipid metabolism was examined in brain regions previously inaccessible due to their small volumes. METHOD: Three-dimensional chemical-shift imaging (3D-CSI) examined 15 cc volumes in 12 brain regions in 11 people with chronic schizophrenia and 11 healthy control volunteers. RESULTS: Glycerophosphoethanolamine was decreased in the anterior cingulate, right prefrontal cortex and left thalamus, but increased in the left hippocampus and cerebellum in those with schizophrenia. Phosphoethanolamine and glycerophosphocholine were decreased in the right prefrontal region and phosphocholine was decreased in the anterior cingulate. No significant difference in membrane phospholipid levels existed between groups in the parieto-occipital and posterior cingulate regions. CONCLUSIONS: Altered membrane phospholipid metabolism was demonstrated in all regions implicated in schizophrenia. PMID- 11772851 TI - Signs and Symptoms of Psychotic Illness (SSPI): a rating scale. AB - BACKGROUND: In the rating scales commonly used for assessing response to antipsychotic treatment, individual items embrace symptoms that apparently arise from distinguishable pathophysiological processes and might be expected to respond differently to treatment. AIMS: To test the reliability, sensitivity to change and factor structure of a new scale for the assessment of the Signs and Symptoms of Psychotic Illness (the SSPI). METHOD: Interrater reliability was evaluated by determining the intraclass correlation for the ratings of 63 patients. Sensitivity to change was assessed in a longitudinal study of 33 patients. Factor structure was determined from scores for 155 patients. RESULTS: The intraclass correlation was satisfactory for all individual items and excellent for the total score. Scores were sensitive to change. A change in Clinical Global Impression of one unit corresponded to an SSPI total score change of 31%. Factor analysis revealed five clusters of symptoms. CONCLUSIONS: The SSPI provides a sensitive and reliable measure of the five major clusters of symptoms that occur commonly in psychotic illness. PMID- 11772852 TI - Towards a standardised brief outcome measure: psychometric properties and utility of the CORE-OM. AB - BACKGROUND: An acceptable, standardised outcome measure to assess efficacy and effectiveness is needed across multiple disciplines offering psychological therapies. AIMS: To present psychometric data on reliability, validity and sensitivity to change for the CORE-OM (Clinical Outcomes in Routine Evaluation- Outcome Measure). METHOD: A 34-item self-report instrument was-developed, with domains of subjective well-being, symptoms, function and risk. Analysis includes internal reliability, test-retest reliability, socio-demographic differences, exploratory principal-component analysis, correlations with other instruments, differences between clinical and non-clinical samples and assessment of change within a clinical group. RESULTS: Internal and test-retest reliability were good (0.75-0.95), as was convergent validity with seven other instruments, with large differences between clinical and non-clinical samples and good sensitivity to change. CONCLUSIONS: The CORE-OM is a reliable and valid instrument with good sensitivity to change. It is acceptable in a wide range of practice settings. PMID- 11772853 TI - Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS LD). AB - BACKGROUND: The Health of the Nation Outcomes Scales (HoNOS) have been developed to measure outcomes in people with mental health problems. AIMS: Frequent impaired social functioning, problems with communication and associated physical conditions meant that a bespoke instrument was needed for people with learning disabilities. We describe the development of the Health of the Nation Outcomes Scales for People with Learning Disabilities (HoNOS-LD). METHOD: HoNOS-LD was piloted at 26 sites. Two raters, at two points in time, rated 372 subjects. Analysis determined acceptability, ease of use, interrater reliability, sensitivity to change and reliability with the Aberrant Behavior Checklist (ABC). RESULTS: The resulting 18-item instrument demonstrated good reliability and validity characteristics and is generally acceptable to clinicians. CONCLUSIONS: HoNOS-LD is an appropriate instrument for measuring outcome in people with learning disabilities with additional mental health needs. PMID- 11772854 TI - Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS LD): glossary for HoNOS-LD score sheet. PMID- 11772855 TI - Subjective experience of a confusional state. AB - BACKGROUND: Confusional states associated with medical and surgical conditions require more study and biochemical explanation. AIMS: To understand impairment of consciousness, cognition and memory. METHOD: A psychiatrist reports experience of his changing mental state over 5 days from notes made immediately on recovery. RESULTS: A prodromal phase of declining consciousness, understanding and memory registration over perhaps 48 h was difficult to detect. During unconsciousness there were four brief partial reversals with arousal, and some mental functioning (memory, formation of beliefs) occurred. CONCLUSIONS; Self-report can be a useful addition in clinical study, and patients with renal failure require psychological and psychiatric study. Comparison with the mental effects of benzodiazepine or of an anaesthetic such as nitrous oxide might throw light on the pathology. PMID- 11772856 TI - Impact of a mother-infant intervention in an indigent peri-urban South African context: pilot study. AB - BACKGROUND: A high rate of maternal depression and associated disturbance in the mother-infant relationship has been found in an indigent peri-urban South African community, Khayelitsha. The question arises whether a community-based intervention could be beneficial. AIMS: To train community workers to deliver an intervention to mothers and infants in Khayelitsha, and to compare mothers and infants receiving this intervention with a sample receiving no such intervention. METHOD: Four Khayelitsha women were trained in a mother-infant intervention, which they delivered to 32 women recruited in late pregnancy. At 6 months post partum, maternal mood, the mother-infant relationship and infant growth were assessed. The findings were compared with a matched group of 32 mothers and infants. RESULTS: There was no reliable impact of the intervention on maternal mood. However, compared with the comparison sample, the quality of mother-infant engagement was significantly more positive for those who had received the intervention. CONCLUSIONS: The pilot study produced preliminary evidence of a benefit of a community-based mother-infant intervention delivered by trained, but otherwise unqualified, community workers, sufficient to warrant a formal controlled evaluation of this treatment. PMID- 11772857 TI - Conflict of interest and the British Journal of Psychiatry. PMID- 11772858 TI - Risk of pregnancy when changing to atypical antipsychotics. PMID- 11772859 TI - Hospitalisation in first-episode psychosis. PMID- 11772860 TI - Use of antidepressants by nursing mothers. PMID- 11772861 TI - Antipsychotics and risk of venous thrombosis. PMID- 11772862 TI - Reforming the Mental Health Act--recruitment and retention issues. PMID- 11772866 TI - On evolutionary biology, inflammation, infection, and the causes of atherosclerosis. PMID- 11772867 TI - Detection of myocardial ischemia in patients with diabetes mellitus. PMID- 11772868 TI - Still stressed out but doing fine: normalization of wall stress is superfluous to maintaining cardiac function in chronic pressure overload. PMID- 11772869 TI - Increased plasma C-reactive protein in familial hypoalphalipoproteinemia: a proinflammatory condition? AB - BACKGROUND: HDL molecules have an established role in the regression processes of atherosclerosis as well as a putative role as antiinflammatory agents. Our study investigated whether familial hypoalphalipoproteinemia, a genetic form of dyslipidemia characterized by very low HDL levels, might be associated with increased inflammation markers such as C-reactive protein. METHODS AND RESULTS: A total of 50 subjects with hypoalphalipoproteinemia (age, 53.1+/-16.7 years) were compared with 64 healthy controls (age, 51.9+/-12.4 years). Apart from significantly lower values of HDL cholesterol (30.2+/-4.0 versus 52.5+/-12.7 mg/dL, P<0.0001) and apolipoprotein AI (113.3+/-20.0 versus 155.4+/-24.9 mg/dL, P<0.0001) and higher levels of triglycerides (141.3+/-62.9 versus 73.5+/-39.9 mg/dL, P<0.0001), patients did not show different plasma values of total cholesterol and LDL cholesterol when compared with healthy controls (181.5+/-36.6 versus 186.3+/-32.6 mg/dL; 123.0+/-31.5 versus 119.1+/-30.3 mg/dL). CRP plasma values were significantly higher in patients than in controls (median 0.34 [range 0.02 to 4.66] versus 0.07 [0.02 to 0.85] mg/dL, P<0.0001). In the patient group, CRP values were significantly higher in subjects with angiographically documented coronary atherosclerotic disease than in those without. Moreover, CRP concentrations were inversely correlated with both HDL cholesterol (r= -0.44, P=0.0006) and apolipoprotein AI (r= -0.45, P=0.0006) values. CONCLUSIONS: Elevation of C-reactive protein values in familial hypoalphalipoproteinemia, in the absence of signs and symptoms of local or systemic inflammation or systemic or recurrent disease, may suggest an upregulation of proinflammatory mechanisms, which is further exacerbated by the presence of coronary atherosclerotic disease. PMID- 11772870 TI - Impact of infectious burden on extent and long-term prognosis of atherosclerosis. AB - BACKGROUND: Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. METHODS AND RESULTS: In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against H pylori (P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (> or =2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens. CONCLUSIONS: Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis. PMID- 11772871 TI - Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. AB - BACKGROUND: Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non-protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD. METHODS AND RESULTS: A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L; P<0.001). FMD improved at 2 hours (83 compared with 47 microm; P<0.001) and was largely complete by 4 hours (101 compared with 51 microm; P<0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 micromol/L; P=NS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 micromol/L; P=0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time. CONCLUSIONS: These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine. PMID- 11772872 TI - Clinical and echocardiographic characteristics of patients with left atrial thrombus and sinus rhythm: experience in 20 643 consecutive transesophageal echocardiographic examinations. AB - BACKGROUND: Left atrial (LA) thrombus is infrequently detected in the presence of sinus rhythm (SR) and, in these cases, is usually associated with additional cardiac pathologies. We sought to determine the clinical and echocardiographic characteristics of patients with LA thrombus and SR to define a high-risk group of patients prone to this uncommon clinical presentation. METHODS AND RESULTS: The institution's echocardiographic laboratory database was searched to identify patients with LA thrombus, diagnosed by transesophageal echocardiography (TEE), who were in SR during the TEE examination. Of 20 643 consecutive TEE examinations performed during an 11-year period, LA thrombus was detected in 314 patients in 380 TEE examinations. Of these, SR was present in 20 patients (age 69+/-13 years; 40% men) in 23 examinations (0.1% of all TEE examinations; 6.1% of TEE examinations with LA thrombus). High-risk structural heart disease (severe left ventricular dysfunction or significant left-sided valve disease [predominantly mitral valve disease]), previous documented episodes of atrial fibrillation, or both (structural heart disease and previous atrial fibrillation) were present in 10, 4, and 5 of the 20 patients, respectively. Only 1 patient with LA thrombus and SR did not have high-risk features. CONCLUSIONS: LA thrombus is very infrequently detected in the presence of SR. Patients with LA thrombus and SR constitute a high-risk group characterized by specific structural cardiac abnormalities or previous atrial fibrillation, abnormalities that are potentially detectable before TEE. PMID- 11772873 TI - Impact of diabetes on the risk stratification using stress single-photon emission computed tomography myocardial perfusion imaging in patients with symptoms suggestive of coronary artery disease. AB - BACKGROUND: Coronary artery disease can develop prematurely and is the leading cause of death among diabetics, making noninvasive risk stratification desirable. METHODS AND RESULTS: Patients with symptoms of coronary artery disease who were undergoing stress myocardial perfusion imaging (MPI) from 5 centers were prospectively followed (2.5+/-1.5 years) for the subsequent occurrence of cardiac death, myocardial infarction (MI), and revascularization. Stress MPI results were categorized as normal or abnormal (fixed or ischemic defects and 1, 2, or 3 vessel distribution). Of 4755 patients, 929 (19.5%) were diabetic. Patients with diabetes, despite an increased revascularization rate, had 80 cardiac events (8.6%; 39 deaths and 41 MIs) compared with 172 cardiac events (4.5%; 69 deaths and 103 MIs) in the nondiabetic cohort (P<0.0001). Abnormal stress MPI was an independent predictor of cardiac death and MI in both populations. Diabetics with ischemic defects had an increased number of cardiac events (P<0.001), with the highest MI rates (17.1%) observed with 3-vessel ischemia. Similarly, a multivessel fixed defect was associated with the highest rate of cardiac death (13.6%) among diabetics. The unadjusted cardiac survival rate was lower for diabetic patients (91% versus 97%, P<0.001), but it became comparable once adjusted for the pretest clinical risk and stress MPI results. In multivariable Cox analysis, both ischemic and fixed MPI defects independently predicted cardiac death alone or cardiac death/MI. Diabetic women had the worst outcome for any given extent of myocardial ischemia. CONCLUSIONS: In this large cohort of diabetics undergoing stress MPI, the presence and the extent of abnormal stress MPI independently predicted subsequent cardiac events. Using stress MPI in conjunction with clinical information can provide risk stratification of diabetic patients. PMID- 11772874 TI - Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension. AB - BACKGROUND: The SA gene (SAH) has been isolated by differential screening from a genetically hypertensive rat strain as a candidate gene that may contribute to hypertension. Recently, the SA protein has been reported to be highly homologous to bovine xenobiotic-metabolizing medium-chain fatty acid:CoA ligase. METHODS AND RESULTS: To clarify the pathophysiological significance of SAH, we searched for polymorphisms of human SAH and performed association studies using a large cohort (4000 subjects) representing the general population in Japan. We found 2 polymorphisms in the promoter region and single-nucleotide polymorphisms in introns 5, 7, and 12 and exon 8. One of the variants, an A/G polymorphism in intron 12, just 7 bp upstream from exon 13, strongly affected plasma triglyceride, plasma cholesterol, body mass index (BMI), waist-to-hip ratio (W/H), and blood pressure status. The effect of this genotype on blood pressure seems to be conveyed through its effects on BMI and W/H. Transient expression of the SA protein in mammalian cells confirmed that it is expressed in mitochondria and has medium-chain fatty acid:CoA ligase activity. The A/G polymorphism was found to be associated with the expression level of SA mRNA in peripheral mononuclear cells in vivo. CONCLUSIONS: The G allele of SAH was found to be associated with multiple risk factors, including hypertriglyceridemia, hypercholesterolemia, obesity, and hypertension. This observation should open a new area for future research in multiple-risk-factor syndromes. PMID- 11772875 TI - Antecedent blood pressure and risk of cardiovascular disease: the Framingham Heart Study . AB - BACKGROUND: Casual blood pressure (BP) is a powerful predictor of risk of cardiovascular disease (CVD), but a single BP determination may not accurately reflect the residual impact of antecedent BP levels on vascular risk. It is unclear whether time-averaged past BP measures incrementally improve CVD risk assessment. METHODS AND RESULTS: We used sex- and age-specific multivariable Cox regression to evaluate the association of current BP (at baseline), recent antecedent BP (average of readings for all available examinations 1 to 10 years before baseline), and remote antecedent BP (average for all available examinations 11 to 20 years before baseline) with the 10-year risk of CVD in 2313 Framingham Study subjects (910 men, 1403 women) free of CVD at baseline. During follow-up, 899 incident initial CVD events were observed (479 in women). In multivariable models incorporating established CVD risk factors, recent and remote antecedent BP predicted CVD risk incrementally over current BP. This effect was consistent in multiple subgroups: men and women, older and younger age groups, and lower and higher BP groups. The relations of antecedent BP to CVD risk were consistent for systolic BP, diastolic BP, and pulse pressure. CONCLUSIONS: Antecedent BP is an important determinant of future risk of CVD events above and beyond current BP. When available, use of long-term average BP may improve the prognostic utility of conventional CVD risk prediction that is based on current BP. Our findings suggest that effective prevention of CVD requires adequate control of BP throughout life. PMID- 11772876 TI - Gas exchange detection of exercise-induced right-to-left shunt in patients with primary pulmonary hypertension. AB - BACKGROUND: Because of high pulmonary vascular resistance in patients with primary pulmonary hypertension (PPH), right atrial pressure may exceed left atrial pressure during exercise, resulting in a right-to-left shunt via a patent foramen ovale (PFO). This shunting would disturb arterial PCO2 and H+ homeostasis if the pulmonary blood were not simultaneously hyperventilated to compensate for the high CO2 and H+ in the shunted blood. This article first hypothesizes and then describes unique changes in gas exchange when right-to-left exercise-induced shunting (EIS) occurs. METHODS AND RESULTS: Retrospectively, the cardiopulmonary exercise tests of 71 PPH patients were studied. Criteria postulated to document hyperventilation of the pulmonary blood flow due to a right-to-left EIS were (1) an abrupt and sustained increase in end-tidal O2 with a simultaneous sustained decrease in end-tidal CO2; (2) an abrupt and sustained increase in the respiratory exchange ratio; and (3) usually, an associated decline in pulse oximetry saturation. Each patient was evaluated for a PFO with resting echocardiography. The investigators interpreting the gas exchange evidence of EIS were blinded to the echocardiographic readings. Forty-five percent of the patients had demonstrable EIS by gas exchange criteria. Almost all were also positive for a PFO by echocardiography. Using the resting echocardiograph as the reference, the sensitivity, specificity, positive and negative predictive values, and accuracy were all between 90% to 96%. CONCLUSIONS: Exercise-induced right-to left shunting can be detected by noninvasive, cardiopulmonary exercise testing in patients with PPH. PMID- 11772877 TI - Primary aortic valve replacement with cryopreserved aortic allograft: an echocardiographic follow-up study of 570 patients. AB - BACKGROUND: Despite the many advantages of an aortic allograft valve (AAV) over a prosthetic aortic valve, its durability is suboptimal. The aims of the present study were to document characteristic features of AAV dysfunction and to investigate factors influencing the development of such dysfunction. METHODS AND RESULTS: A group of 570 patients (mean age, 48+/-16 years) with a cryopreserved AAV underwent a follow-up echocardiographic study (mean time after surgery, 6.8 years; range, 1.0 to 22.9 years). Significant AAV regurgitation was present in 14.7% of patients, and AAV stenosis was present in 3.2%. The root replacement subgroup had the smallest number of patients with significant AAV regurgitation (5.0%) compared with the subcoronary (23.0%) or the inclusion cylinder technique subgroup (14.7%). After 10 to 15 years after AAV replacement, grade > or =2 AAV dysfunction was present in 40% of patients in the subcoronary subgroup, but no significant dysfunction was observed in patients in the root replacement subgroup (P<0.001). Smaller host aortic annulus size in both subcoronary (coefficient, 0.145; P=0.013) and root replacement subgroups (coefficient, -0.249; P=0.011) was associated with more frequent AAV dysfunction (grade > or =2). In addition, significant AAV dysfunction was more frequent when patients were younger (coefficient, -0.020; P=0.015) in the subcoronary subgroup and the donor was older (coefficient, 0.054; P=0.019) in the root replacement subgroup. CONCLUSIONS: The present study indicates that the root replacement technique is associated with less frequent AAV degeneration. Our findings should help in establishing more strict selection criteria for surgical replacement procedure type and patient/donor factors for AAV replacement and, therefore, could lead to improve AAV longevity. PMID- 11772878 TI - Reversal of angiogenic growth factor upregulation by revascularization of lower limb ischemia. AB - BACKGROUND: Tissue kallikrein (tK) and vascular endothelial growth factor (VEGF) are potent angiogenic agents. Upregulation of tK or VEGF was documented in animal models of acute ischemia, yet it remains unknown whether these endothelial cell mitogens are overexpressed in chronic peripheral vascular insufficiency. METHODS AND RESULTS: Circulating tK and VEGF were measured in 36 patients with symptomatic peripheral vascular disease before and after surgical revascularization. In 6 patients without symptoms at rest, tK was assayed after exercise stress test. VEGF levels fell within the normal range in all patients (96+/-11 versus 109+/-13 pg/mL in healthy control subjects, P=NS) and remained unchanged after revascularization. In contrast, tK expression was upregulated in 34 of 36 patients (1107+/-203 versus 85+/-10 pg/mL in control subjects, P<0.05), with no further increase after exercise. Tissue kallikrein levels in the venous effluent of ischemic limbs were found to be positively correlated with the number of angiographically recognizable collateral vessels (P<0.001). Follow-up studies documented reversal of tK upregulation after revascularization (P<0.01), whereas no change was observed in venous samples from untouched legs. CONCLUSIONS: Induction of tK could represent a compensatory response to chronic arterial insufficiency, attempting to maintain an adequate tissue perfusion. Heterogeneous statement of growth factors may have important implications in reparative and therapeutic angiogenesis. PMID- 11772879 TI - Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. AB - BACKGROUND: The electrocardiographic pattern of right bundle-branch block with ST segment elevation in leads V1 to V3 is increasingly recognized among patients who have aborted sudden cardiac death, but also in asymptomatic individuals, raising questions about its prognostic significance. METHODS AND RESULTS: The clinical, electrophysiological, and follow-up data of 334 patients with the Brugada phenotype were analyzed. A total of 79 women and 255 men with a mean age at diagnosis of 42+/-16 years were studied. The abnormal ECG was recognized after a resuscitated cardiac arrest in 71 patients (group A), after a syncopal episode in 73 patients (group B), and in 190 asymptomatic individuals (group C). Sustained ventricular arrhythmias were inducible in 83%, 63%, and 33% of patients in group A, group B, and group C, respectively. During 54+/-54 and 26+/-36 months of follow-up, respectively, 62% of patients in group A and 19% of group B patients had a new arrhythmic event. Inducibility of ventricular arrhythmias was the only predictor of arrhythmia occurrence in both groups. During a mean follow-up of 27+/-29 months, 8% of group C individuals had a first arrhythmic event. In these individuals, inducibility of ventricular arrhythmias and a basal abnormal ECG were predictors of arrhythmia occurrence. CONCLUSIONS: An ECG showing right bundle-branch block and ST-segment elevation in the right precordial leads is a marker of malignant ventricular arrhythmias and sudden death. Recurrence of malignant arrhythmias is high after the occurrence of symptoms. Among asymptomatic individuals, those with a spontaneously abnormal ECG and inducible to ventricular arrhythmias have the poorer prognosis. PMID- 11772880 TI - Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells. AB - BACKGROUND: Heme oxygenase-1 (HO-1) catalyzes the degradation of heme into biliverdin, iron, and carbon monoxide (CO). Although HO-1 is induced in vascular smooth muscle cells (SMCs), the biological role of HO-1 in these cells has not been completely characterized. METHODS AND RESULTS: In the present study, we overexpressed HO-1 in rat aortic SMCs by generating a recombinant defective adenovirus containing the rat HO-1 gene (AdHO-1) and examined the effect on SMC proliferation. Infection of SMCs with AdHO-1 resulted in a dose-dependent increase in the expression of HO-1 mRNA, protein, and activity. Infection of SMCs with AdHO-1 inhibited serum-stimulated SMC proliferation in a dose-dependent manner. In contrast, the control adenovirus expressing the green fluorescent protein failed to induce HO-1 expression and had minimal effects on SMC growth. Infection with AdHO-1 stimulated SMC apoptosis in a dose-dependent fashion, as demonstrated by DNA fragmentation, positive annexin V labeling, and caspase-3 activation. HO-1-mediated apoptosis was associated with a marked increase in the expression of the proapoptotic protein p53. Finally, the exogenous administration of biliverdin and bilirubin stimulated SMC apoptosis. In contrast, the administration of CO or iron failed to induce cell death. CONCLUSIONS: These results demonstrate that overexpression of HO-1 or the exogenous administration of biliverdin or bilirubin stimulates SMC apoptosis. Adenovirus-mediated transfer of the HO-1 gene may provide a novel therapeutic approach in treating occlusive vascular disease. PMID- 11772881 TI - Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress. AB - BACKGROUND: A long-standing hypothesis has been that hypertrophy is compensatory and by normalizing wall stress acts to maintain normal cardiac function. Epidemiological data, however, have shown that cardiac hypertrophy is associated with increased mortality, thus casting doubt on the validity of this hypothesis. METHODS AND RESULTS: To determine whether cardiac hypertrophy is necessary to preserve cardiac function, we used 2 genetically altered mouse models that have an attenuated hypertrophic response to 8 weeks of pressure overload. End-systolic wall stress (sigma(es)) obtained by sonomicrometry after 1 week of pressure overload showed complete normalization of sigma(es) in pressure-overloaded wild type mice (287+/-39 versus sham, 254+/-34 g/cm2), whereas the blunted hypertrophic response in the transgenic mice was inadequate to normalize sigma(es) (415+/-81 g/cm2, P<0.05). Remarkably, despite inadequate normalization of sigma(es), cardiac function as measured by serial echocardiography showed little deterioration in either of the pressure-overloaded genetic models with blunted hypertrophy. In contrast, wild-type mice with similar pressure overload showed a significant increase in chamber dimensions and progressive deterioration in cardiac function. Analysis of downstream signaling pathways in the late stages of pressure overload suggests that phosphoinositide 3-kinase may play a pivotal role in the transition from hypertrophy to heart failure. CONCLUSIONS: These data suggest that under conditions of pressure overload, the development of cardiac hypertrophy and normalization of wall stress may not be necessary to preserve cardiac function, as previously hypothesized. PMID- 11772882 TI - Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. AB - BACKGROUND: Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium. METHODS AND RESULTS: A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, beta-myosin heavy chain, alpha-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs. CONCLUSIONS: The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty. PMID- 11772883 TI - Doppler-derived myocardial systolic strain rate is a strong index of left ventricular contractility. AB - BACKGROUND: Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone. METHODS AND RESULTS: TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance-high-fidelity pressure catheter. Peak elastance (Emax) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (Sm) and peak (epsilon'(p)) and mean (epsilon'(m)) strain rates obtained at the basal septum were compared against Emax by linear regression. Emax as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between Emax and epsilon'(p) (r=0.94, P<0.01, y=0.29x+0.46) and epsilon'(m) (r=0.88, P<0.01) than for Sm (r=0.75, P<0.01). CONCLUSIONS: TDE-derived epsilon'(p) and epsilon'(m) are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S(m), perhaps by eliminating translational artifact. PMID- 11772885 TI - Analysis of mural cell recruitment to tumor vessels. AB - BACKGROUND: Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells. METHODS AND RESULTS: We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and highly abnormal organization of mural cells. Transplantation of tumors to mice expressing lacZ in mural cells demonstrated that these cells were host-derived. Although tumor vessel endothelium expressed PDGF-B, an embryonic mitogen for mural cells, only very few PDGFRbeta-positive cells were found to be associated with the developing tumor vasculature, suggesting a limited pool of recruitable mural cells. We tested whether exogenous mural cells could be recruited to tumor vessels by injecting mixtures of T241 tumor cells and embryonic mesenchymal cells isolated from mice expressing lacZ in mural cells. In the tumors that arose, lacZ-positive cells were efficiently recruited to the tumor vessels. CONCLUSIONS: T241 and KRIB tumors show a similar highly abnormal organization of vessel-associated mural cells. T241 tumor vessels seem highly capable of recruiting exogenously added mural cells. The sparse mural cell coat of tumor vessels may result from a limited pool of mural cells available for recruitment. PMID- 11772884 TI - Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage. AB - BACKGROUND: Adrenomedullin (AM), a potent vasodilator peptide, is produced by posttranslational splicing of pro-adrenomedullin together with proadrenomedullin N-terminal 20 peptide (PAMP), another hypotensive peptide. Although both AM and PAMP have the potential not only to decrease blood pressure but also to protect organs from damage, there is no direct evidence for their individual physiological roles in vivo. METHODS AND RESULTS: Using knockout mice with the disruption of AM peptide alone, we investigated the organ-protective effect of AM. Although the AM(-/-) mutation in mice was embryonic lethal without any apparent phenotypic changes, AM(+/-) mice were viable and fertile; plasma and organ AM concentrations were almost half of those in AM(+/+) mice. With the administration of angiotensin II (Ang II) on a high-salt diet for 12 days, marked perivascular fibrosis and intimal hyperplasia were found in coronary arteries of Ang II/salt-treated AM(+/-) mice, without the AM upregulation that was observed in Ang II/salt-treated AM(+/+) mice. In AM(+/-) mice, Ang II/salt loading increased both urinary excretion of 8-hydroxydeoxyguanosine and isoprostane, markers of oxidative stress. Consistently, immunostaining of both p67phox and gp91phox, subunits of NAD(P)H oxidase and 3-nitrotyrosine, the metabolites of reactive oxygen species (ROS), and the generation of ROS measured by electron spin resonance spectroscopy apparently increased in the Ang II/salt-treated heart. These data suggested that the overproduction of oxidative stress might be involved in the cardiovascular changes induced by Ang II/salt loading. CONCLUSIONS: The evidence presented supports the hypothesis that endogenous AM possesses a protective action against cardiovascular damage, possibly through the inhibition of oxidative stress production. PMID- 11772886 TI - Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor. AB - BACKGROUND: The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A1 receptor (A1AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility. METHODS AND RESULTS: The effects of CVT-2759 and adenosine, a partial and a full agonist of the A1AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT 2759 (10 micromol/L) and adenosine (10 micromol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca2+ current. Increasing the concentration of the full agonist adenosine from 10 to 100 micromol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 micromol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K+ current nor shortened the duration of the atrial APD. CONCLUSIONS: The present results support the hypothesis and suggest a potential role for a partial agonist of the A1AdoR in the treatment of cardiac arrhythmias. PMID- 11772887 TI - Use of an inspiratory impedance valve improves neurologically intact survival in a porcine model of ventricular fibrillation. AB - BACKGROUND: This study evaluated the potential for an inspiratory impedance threshold valve (ITV) to improve 24-hour survival and neurological function in a pig model of cardiac arrest. METHODS AND RESULTS: Using a randomized, prospective, and blinded design, we compared the effects of a sham versus active ITV on 24-hour survival and neurological function. After 6 minutes of ventricular fibrillation (VF), followed by 6 minutes of cardiopulmonary resuscitation (CPR) with either a sham or an active valve, anesthetized pigs received 3 sequential 200-J shocks. If VF persisted, they received epinephrine (0.045 mg/kg), 90 seconds of CPR, and 3 more 200-J shocks. A total of 11 of 20 pigs (55%) in the sham versus 17 of 20 (85%) in the active valve group survived for 24 hours (P<0.05). Neurological scores were significantly higher with the active valve; the cerebral performance score (1=normal, 5=brain death) was 2.2+/-0.2 with the sham ITV versus 1.4+/-0.2 with the active valve (P<0.05). A total of 1 of 11 in the sham versus 12 of 17 in the active valve group had completely normal neurological function (P<0.05). Peak end-tidal CO2 (PETCO2) values were significantly higher with the active valve (20.4+/-1.0) than the sham (16.8+/ 1.5) (P<0.05). PETCO2 >18 mm Hg correlated with increased survival (P<0.05). CONCLUSIONS: Use of a functional ITV during standard CPR significantly improved 24-hour survival rates and neurological recovery. PETCO2 and systolic blood pressure were also significantly higher in the active valve group. These data support further evaluation of ITV during standard CPR. PMID- 11772888 TI - Images in cardiovascular medicine. Coronary thrombosis and myocardial bridging. PMID- 11772889 TI - Images in cardiovascular medicine. Rupture of aneurysm of the right sinus of Valsalva into the right ventricular outflow tract: treatment with Amplatzer atrial septal occluder. PMID- 11772890 TI - Myocardial infarction and oral contraceptives. PMID- 11772892 TI - Staying the course--with a few adjustments. PMID- 11772893 TI - Impact of computer-generated personalized goals on HbA(1c). AB - OBJECTIVE: The public is increasingly aware of the importance of HbA(1c) testing, yet the vast majority of patients with diabetes do not know their HbA(1c) status or goal. We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c) levels. RESEARCH DESIGN AND METHODS: A total of 150 patients with diabetes were randomized to receive either standard care or intervention inclusive of a computer-generated 11" x 17" color poster depicting an individual's HbA(1c) status and goals along with personalized steps to aid in goal achievement. All patients enrolled received diabetes education during the 3 months before enrollment. HbA(1c) was performed at baseline and 6 months. RESULTS: At baseline, there were no significant differences between patient groups in terms of age, sex, education level, race, and HbA(1c) or lipid levels. Among patients with baseline HbA(1c) > or =7.0%, there was an 8.6% (0.77% absolute) reduction in HbA(1c) among control subjects compared with a 17.0% (1.69% absolute) decline in the intervention group (P = 0.032). There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c) (63 vs. 69%, P = 0.87); among these patients experiencing a decline, the most substantial reductions were seen with the control group, which had a 13.3% (1.15% absolute) decline compared with the intervention patients, who reduced their HbA(1c) by 24.2% (2.26% absolute reduction; P = 0.0048). At study close, 77% of the patients had their poster displayed on their refrigerator. CONCLUSIONS: This unique and personalized computer-generated intervention resulted in HbA(1c) lowering comparable to that of hypoglycemic agents. PMID- 11772894 TI - The impact of outpatient diabetes management on serum lipids in urban African Americans with type 2 diabetes. AB - OBJECTIVE: Treating dyslipidemia in diabetic patients is essential, particularly among minority populations with increased risk of complications. Because little is known about the impact of outpatient diabetes management on lipid outcomes, we examined changes in lipid profiles in urban African-Americans who attended a structured diabetes care program. RESEARCH DESIGN AND METHODS: A retrospective analysis of initial and 1-year follow-up lipid values was conducted among patients selected from a computerized registry of an urban outpatient diabetes clinic. The independent effects of lipid-specific medications, glycemic control, and weight loss on serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were evaluated by analysis of covariance and multiple linear regression. RESULTS: In 345 patients (91% African-American and 95% with type 2 diabetes), HbA(1c) decreased from 9.3% at the initial visit to 8.2% at 1 year (P < 0.001); total and LDL cholesterol and triglyceride levels were significantly lower, and HDL cholesterol was higher. After stratifying based on use of lipid specific therapy, different outcomes were observed. In 243 patients not taking dyslipidemia medications, average total cholesterol, LDL cholesterol, and triglyceride concentrations at 1 year were similar to initial values, whereas in 102 patients receiving pharmacotherapy, these lipid levels were all lower at 1 year relative to baseline (P < 0.001). Mean HDL cholesterol increased regardless of lipid treatment status (P < 0.001). After adjusting for other variables, changes in LDL cholesterol concentration were associated only with use of lipid specific agents (P = 0.003), whereas improved HbA(1c) and weight loss had no independent effect. Lipid therapy, improved glycemic control, and weight loss were not independently related to changes in HDL cholesterol and therefore could not account for the positive changes observed. Use of lipid-directed medications, improvement in glycemic control, and weight loss all resulted in significant declines in triglyceride levels but only improved HbA(1c) and weight loss had an independent effect. CONCLUSIONS: Among urban African-Americans, diabetes management led to favorable changes in HDL cholesterol and triglyceride levels, but improved glycemic control and weight loss had no independent effect on LDL cholesterol concentration. Initiation of pharmacologic therapy to treat high LDL cholesterol levels should be considered early in the course of diabetes management to reach recommended targets and reduce the risk of cardiovascular complications in this patient population. PMID- 11772895 TI - Long-term impact of neonatal breast-feeding on body weight and glucose tolerance in children of diabetic mothers. AB - OBJECTIVE: Offspring born to women with pregnancies complicated by diabetes are at increased childhood risk of developing obesity and impaired glucose tolerance (IGT). In population-based studies, breast-feeding has been shown to be protective against obesity and diabetes later in life. To date, the role of breast-feeding on offspring of diabetic mothers (ODM) has not been investigated in this context. RESEARCH DESIGN AND METHODS: A total of 112 ODM (type 1 diabetes, n = 83; gestational diabetes, n = 29) were evaluated prospectively for impact of ingestion of either diabetic breast milk (DBM) or nondiabetic banked donor breast milk (BBM) during the early neonatal period (day 1-7 of life) on relative body weight and glucose tolerance at a mean age of 2 years. RESULTS: There was a positive correlation between the volume of DBM ingested and risk of overweight at 2 years of age (odds ratio [OR] 2.47, 95% CI 1.25-4.87). In contrast, the volume of BBM ingested was inversely correlated to body weight at follow-up (P = 0.001). Risk of childhood IGT decreased by increasing amounts of BBM ingested neonatally (OR 0.19, 95% CI 0.05-0.70). Stepwise regression analysis showed volume of DBM to be the only significant predictor of relative body weight at 2 years of age (P = 0.001). CONCLUSIONS: Early neonatal ingestion of breast milk from diabetic mothers may increase risk of becoming overweight and, consequently, developing IGT during childhood. Additional studies are needed to assess long-term consequences that might result from the type of neonatal nutrition in ODM. PMID- 11772896 TI - Productivity and medical costs of diabetes in a large employer population. AB - OBJECTIVE: The purpose of this study was to assess the economic burden of diabetes from an employer's perspective. We analyzed the costs of diabetes, using claims data for an employed population and the prevalence of selected comorbid conditions. RESEARCH DESIGN AND METHODS: The data source is a claims database from a national Fortune 100 manufacturer. It includes medical, pharmacy, and disability claims for all beneficiaries (n >100,000). Both medical and work productivity costs of diabetes patients are compared by age with those of matched control subjects from the overall beneficiary population. Out-of-pocket and intangible costs are excluded. RESULTS: In 1998, the employer's mean annual per capita costs were higher for all diabetes beneficiaries than for control subjects ($7,778 +/- 16,176 vs. $3,367 +/- 8,783; P < 0.0001), yielding an incremental cost of $4,410 +/- 18,407 associated with diabetes. The medical and productivity costs for employees with diabetes were significantly (P < 0.0008) higher than for control subjects. The incremental cost of diabetes among employees ranged from $4,671 (aged 18-35 years) to $4,369 (aged 56-64 years). CONCLUSIONS: Diabetes imposes a significant economic burden on employers, particularly when including productivity costs. Employers should select health plans that provide enriched benefits to diabetes patients, including ready access to medical and pharmacy services as well as aggressive diabetes management programs. PMID- 11772897 TI - Stress management improves long-term glycemic control in type 2 diabetes. AB - OBJECTIVE: There is conflicting evidence regarding the utility of stress management training in the treatment of diabetes. The few studies that have shown a therapeutic effect of stress management have used time-intensive individual therapy. Unfortunately, widespread use of such interventions is not practical. The aim of the present investigation is to determine whether a cost-effective, group-based stress management training program can improve glucose metabolism in patients with type 2 diabetes and to determine whether a particular subset of patients is more likely to get positive results. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes were randomized to undergo a five-session group diabetes education program with or without stress management training. Participants (n = 108) were followed for 1 year, during which HbA(1c) tests and questionnaires assessing perceived stress, anxiety, and psychological health were administered at regular intervals to evaluate treatment effects. RESULTS: Stress management training was associated with a small (0.5%) but significant reduction in HbA(1c). Compliance with the treatment regimen decreased over time but was similar to that seen in patients receiving stress management for other reasons in the clinic. Trait anxiety (a measure of stable individual differences in anxiety proneness) did not predict response to treatment, showing that highly anxious patients did not derive more benefit from training. CONCLUSIONS: The current results indicate that a cost-effective, group stress management program in a "real-world" setting can result in clinically significant benefits for patients with type 2 diabetes. PMID- 11772898 TI - The network of psychological variables in patients with diabetes and their importance for quality of life and metabolic control. AB - OBJECTIVE: The primary goals in treating patients with diabetes are maintaining blood glucose levels as close to normal as possible and making a relatively normal quality of life achievable. Both of these goals are influenced by a multitude of somatic and psychological factors that should be seen as building a complex network. We examined whether a mathematical model can be construed that can depict the relative significance of each factor for achieving these treatment goals. RESEARCH DESIGN AND METHODS: A total of 625 patients from 32 different treatment facilities were examined (224 type 1 and 401 type 2 diabetic patients) using HbA(1c) values (high-performance liquid chromatography), number of secondary illnesses, and standardized questionnaires with respect to health related quality of life (World Health Organization Quality of Life questionnaire), coping behavior (Freiburger Illness-Coping Strategies questionnaire), diabetes-specific knowledge (Test of Diabetes-Specific Knowledge), doctor-patient relationship (Medical Interview Satisfaction Scale), and personality characteristics (Giessen Test and Assessment of Beliefs in Self Efficacy and Optimism). The analyses were carried out by means of a structural equation model. RESULTS: The model proved to be valid (chi(2) = 88.5, df = 76, P = 0.16), showing a sound fit (adjusted goodness of fit [AGFI] = 0.94). It explained 62% of the variance of the quality of life and 5% of the HbA(1c) values. Subjects characterized by strong beliefs in their self-efficacy and an optimistic outlook on life were more likely to be satisfied with their doctor patient relationships. They demonstrated more active coping behavior and proved to have a higher quality of life. Active coping behavior was the only psychological variable significant for the HbA(1c) values. CONCLUSIONS: It was possible to illustrate the various factors involved and their mutual dependency and significance for the treatment goals. Belief in self-efficacy and active coping behavior appear to have the greatest relevance for achieving the primary treatment goals. PMID- 11772899 TI - Cause-specific mortality in a population with diabetes: South Tees Diabetes Mortality Study. AB - OBJECTIVE: To describe the mortality of a population with diabetes compared with the local nondiabetic population, using age-, sex-, and cause-specific death rates and relative and absolute differences in death rates. RESEARCH DESIGN AND METHODS: A population-based cohort of 4,842 people with diabetes living within South Tees, U.K., was identified and followed from 1 January 1994 to 31 December 1999. Causes of death were obtained from death certificates, and mortality rates were compared with the nondiabetic population of the same area for the same time period. RESULTS: There were 1,205 deaths (24.9%) in the study population during the 6 years of study. For type 2 diabetes, mortality from cardiovascular causes was significantly increased in both sexes and at all ages. Relative death rates for the age band 40-59 years were 5.47 (95% CI 4.18-7.15) for men and 5.60 (3.44 9.14) for women. The relative death rates declined with age for both sexes, but absolute excess mortality increased with age. There were no consistent differences in noncardiovascular death rates, other than for renal disease. Similar outcomes were found for type 1 diabetes, although these results were limited by a much smaller population size. People with diabetes and renal impairment had significantly higher mortality than people with diabetes alone, with a rate ratio of 7.27 for people with type 2 diabetes aged 40-59 years. CONCLUSIONS: In an area of the U.K. with high cardiovascular death rates, people with diabetes had significantly higher cardiovascular death rates than people without diabetes. Interventions targeted at cardiovascular risk factors should be used to try and reduce this excess premature mortality, which is especially high in those with renal impairment. PMID- 11772900 TI - Incidence of diabetes in American Indians of three geographic areas: the Strong Heart Study. AB - OBJECTIVE: To estimate incidence rates of diabetes and associated risk factors among participants of the Strong Heart Study. RESEARCH DESIGN AND METHODS: Of the 4,549 Strong Heart Study participants examined at baseline, 3,638 returned for a similar examination after an average of 4 years. The 1985 World Health Organization criteria for diabetes were used to identify new diabetes cases. Rates of diabetes among participants who did not have diabetes at baseline examination were determined. The relationships between the incidence rates of diabetes and a number of risk factors measured at baseline examination were studied. RESULTS: Significant variables associated with the development of diabetes included triglycerides, obesity, fasting plasma glucose, insulin, and degree of American Indian blood among participants with NGT at baseline. For those with IGT at baseline, significant predictors included fasting plasma glucose, 2-h glucose, BMI, degree of American Indian blood, and albuminuria. CONCLUSIONS: The high incidence rates found in this study were alarming. To slow down the rapid increase of this disease in the American Indian population, preventive programs must be designed and implemented. Patients with IGT should be treated with diabetes medication or put on a rigid weight-reduction program to reduce the risk of progression to diabetes. PMID- 11772901 TI - Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. AB - OBJECTIVE: To determine the prospective association between endogenous sex hormones and the development of type 2 diabetes in older men and women. RESEARCH DESIGN AND METHODS: A standardized medical history was obtained, an oral glucose tolerance test was performed, and plasma samples for sex hormones and covariates were collected from ambulatory, community-dwelling men and women at baseline from 1984 to 1987. Approximately 8 years later (1992-1996), another medical history was obtained, an oral glucose tolerance test was performed, fasting and 2-h insulin levels were measured, and the homeostasis model assessment for insulin resistance (HOMA-IR) was evaluated. This report is based on the 294 men and 233 women, aged 55-89 years, who completed both visits and who did not have diabetes as determined by history or glucose tolerance test at baseline, as well as women who were postmenopausal and not taking replacement estrogen. RESULTS: In age adjusted correlation analyses, total testosterone was inversely and significantly related to subsequent levels of fasting and postchallenge glucose and insulin in men, whereas bioavailable testosterone and bioavailable estradiol were positively and significantly related to fasting and postchallenge glucose and insulin in women (all P <0.05). There was similar significant association with insulin resistance (HOMA-IR) in unadjusted and multiply adjusted analyses (P <0.05). There were 26 men and 17 women with new (incident) diabetes. The odds for new diabetes were 2.7 (95% CI 1.1-6.6) for men in the lowest quartile of total testosterone and 2.9 (1.1-8.4) for women in the highest quartile of bioavailable testosterone. CONCLUSIONS: Low testosterone levels in men and high testosterone levels in women predict insulin resistance and incident type 2 diabetes in older adults. PMID- 11772902 TI - Diabetes and incidence of functional disability in older women. AB - OBJECTIVE: To examine the relationship between diabetes and the incidence of functional disability and to determine the predictors of functional disability among older women with diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 8,344 women enrolled in the Study of Osteoporotic Fractures, a prospective cohort of women aged > or =65 years. Diabetes (n = 527, 6.3% prevalence) and comorbidities (coronary heart disease, stroke, arthritis, depression, and visual impairment) were assessed by questionnaire and physical examination. Incident disability, defined as onset of inability to do one or more major functional tasks (walking 0.25 mile, climbing 10 steps, performing household chores, shopping, and cooking meals), was assessed by questionnaire over 12 years. RESULTS: The yearly incidence of any functional disability was 9.8% among women with diabetes and 4.8% among women without diabetes. The age-adjusted hazard rate ratio (HRR) of disability for specific tasks associated with diabetes ranged from 2.12 (1.82-2.48) for doing housework to 2.50 (2.05-3.04) for walking two to three blocks. After adjustment for potential confounders at baseline (BMI, physical activity, estrogen use, baseline functional status, visual impairment, and marital status) and comorbidities (heart disease, stroke, depression, and arthritis), diabetes remained associated with a 42% increased risk of any incident disability and a 53-98% increased risk of disability for specific tasks. Among women with diabetes, older age, higher BMI, coronary heart disease, arthritis, physical inactivity, and severe visual impairment at baseline were each independently associated with disability. CONCLUSIONS: Diabetes is associated with an increased incidence of functional disability, which is likely to further erode health status and quality of life. PMID- 11772903 TI - Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus. AB - OBJECTIVE: To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS: There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1alpha gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS: MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes. PMID- 11772904 TI - Determinants of mild gestational hyperglycemia and gestational diabetes mellitus in a large dutch multiethnic cohort. AB - OBJECTIVE: The purpose of this study was to identify independent determinants of mild gestational hyperglycemia (MGH) and gestational diabetes mellitus (GDM) and to assess the correlation between fasting glucose and C-peptide levels among control, MGH, and GDM women. RESEARCH DESIGN AND METHODS: A total of 1,022 consecutive women were evaluated with a 1-h 50-g glucose challenge test (GCT) at between 16 and 33 weeks of gestation. Women with a capillary whole-blood glucose > or =7.8 mmol/l in the GCT underwent a 3-h 100-g oral glucose tolerance test (OGTT). On the basis of a positive GCT, the women with a positive OGTT were classified as GDM, whereas the women with a negative OGTT were classified as MGH. The following data were collected for all women: age, prepregnancy BMI, ethnicity, clinical and obstetric history, pregnancy outcome, and C-peptide level. RESULTS: A total of 813 women (79.6%) were normal, 138 (13.5%) had MGH, and 71 (6.9%) had GDM. There was a stepwise significant increase in mean fasting glucose (3.6 +/- 0.4, 3.9 +/- 0.4, and 4.7 +/- 0.7 mmol/l, respectively) and C peptide level (0.60 [0.1-2.4], 0.86 [0.3-2.0], and 1.00 [0.5-1.6] nmol/l, respectively) among the three diagnostic groups. Maternal age, non-Caucasian ethnicity, and prepregnancy BMI were associated with GDM, whereas only maternal age and prepregnancy BMI were associated with MGH. A positive correlation between levels of fasting glucose and C-peptide was found in control women (r = 0.39 [95% CI 0.31-0.46]). A similar result was seen in MGH women (r = 0.38 [95% CI 0.23 0.52]), whereas the correlation between fasting glucose and C-peptide was nearly lost in GDM women (r = 0.14 [CI -0.09 to 0.36]). The fasting C-peptide-to-glucose ratio was reduced by 60% in GDM patients versus control subjects and MGH patients (0.41 +/- 0.25 vs. 0.70 +/- 0.20 and 0.73 +/- 0.23, P < 0.001). CONCLUSIONS: Of the well-known independent determinants of GDM, only maternal age and prepregnancy BMI were associated with MGH. It appears that additional factors promoting loss of beta-cell function distinguish MGH from GDM. One of these factors appears to be ethnicity. PMID- 11772905 TI - Strong in body and spirit: lifestyle intervention for Native American adults with diabetes in New Mexico. AB - OBJECTIVE: To determine the effects of a culturally appropriate diabetes lifestyle intervention for Native Americans on risk factors for complications of diabetes. RESEARCH DESIGN AND METHODS: A nonrandomized, community-based diabetes intervention trial was conducted in three Native American sites in New Mexico from 1993-1997. Participants were assigned to intervention or control based on community of residence. Intervention sessions were held approximately 6 weeks apart over approximately 10 months. The intervention was delivered in site A in family and friends (FF) groups (n = 32); site B received the same intervention in one-on-one (OO) appointments (n = 39); and site C received usual medical care (UC) (n = 33) (total participants, n = 104). Primary change in HbA(1c) level was assessed at 1 year. RESULTS: Adjusted mean change in HbA(1c) value varied significantly across the three arms at 1 year (P = 0.05). The UC arm showed a statistically significant increase in adjusted mean HbA(1c) change (1.2%, P = 0.001), whereas both intervention arms showed a small nonsignificant (P > 0.05) increase in the adjusted mean change (0.5% and 0.2% for FF and OO arms, respectively). The increase was statistically significantly smaller in the combined intervention arms (0.4%) compared with the UC arm (1.2%, P = 0.02). CONCLUSIONS: Lifestyle intervention has the potential to substantially reduce microvascular complications, mortality, and health care utilization and costs if the change is sustained over time. PMID- 11772906 TI - Comparison of antigenicity of Hoechst 21PH insulin using either implantable intraperitoneal pump or subcutaneous external pump infusion in type 1 diabetic patients. AB - OBJECTIVE: To assess the antigenicity of the insulin Hoechst 21PH (Hoe21PH) using continuous subcutaneous insulin infusion (CSII) and to compare the antigenicity of this insulin when administered intraperitoneally or subcutaneously. RESEARCH DESIGN AND METHODS; Peritoneal administration of Hoe21PH (Hoechst-Roussel, Somerville, NJ) insulin using implantable devices (continuous peritoneal insulin infusion [CPII]) increases anti-insulin antibody (AIA) levels in type 1 diabetic patients. Intraperitoneal administration, addition of a stabilizer (polyethylene polypropylene glycol), or insulin modifications due to storage in the pump may be involved in this antigenicity. In this nonrandomized study, 24 type 1 diabetic patients were treated with either CSII (n = 11, group 1) or CPII (n = 13, group 2). AIA levels were measured by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) before starting patients on Hoe21PH and again after 3 and 6 months. RESULTS: Patients were comparable in the two groups. AIA levels (RIA) remained stable (24.3 +/- 8.5% [month 0] to 24.9 +/- 8.5.5% [month 6]) in group 1 and increased (21.8 +/- 6.7% [month 0] to 41.8 +/- 6.9% [month 6]) in group 2 (P = 0.005, Wilcoxon's rank-sum test). Using ELISA, AIA remained stable in the patients in group 1 (n = 9; 3.8 +/- 0.8 units/ml [month 0] and 4.1 +/- 1.0 units/ml [month 6]) and tended to increase in the patients in group 2 (n = 12; 4.1 +/- 0.7 units/ml [month 0] to 17.5 +/- 4.6 units/ml [month 6]) (P = 0.07). Comparison of the evolution of AIA formation between the two groups, using RIA at months 0, 3, and 6 showed a significant difference (analysis of variance, P = 0.009). CONCLUSIONS: No increase in AIA levels was demonstrated when Hoe21PH insulin was administered subcutaneously as assessed by two different assays. CPII is proven to be more antigenic than CSII, and this is not related to a specific antigenicity of Hoe21PH insulin. The intraperitoneal route of administration or insulin modifications due to insulin storage in implantable devices might explain this antigenicity. PMID- 11772907 TI - Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. AB - OBJECTIVE: Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10-16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels > or =7.0 and < or =13.3 mmol/l (> or =126 and < or =240 mg/dl), HbA(1c) > or =7.0%, stimulated C-peptide > or =0.5 nmol/l (> or =1.5 ng/ml), and a BMI > 50th percentile for age. RESULTS: Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was -2.4 mmol/l (-42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA(1c) values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin. CONCLUSION: Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients. PMID- 11772908 TI - Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. AB - OBJECTIVE: Many patients with diabetic nephropathy (DN) have levels of albuminuria > 1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS). RESEARCH DESIGN AND METHODS: We performed a randomized double-blind crossover study of 2 months treatment with candesartan cilexetil 8 mg once daily and placebo in addition to previous antihypertensive treatment. We included 18 type 2 diabetic patients with DN fulfilling the above-mentioned criteria. All received recommended doses of ACE inhibitor and, in addition, 15 patients received diuretics, 11 received a calcium channel antagonist, and 3 received a beta blocker. At the end of each treatment period, we measured the glomerular filtration rate (GFR), 24-h blood pressure, albuminuria, and IgGuria. RESULTS: The addition of candesartan to usual antihypertensive therapy induced a mean (95% CI) reduction in albuminuria of 25% (2-58), P = 0.036 (geometric mean [95% CI] from 1,764 mg/24 h [1,225-2,540] to 1,334 mg/24 h [890-1,998]). It also produced a mean reduction of 35% (9-53) in the fractional clearance of albumin (P = 0.016), a reduction of 32% (1-54) in fractional clearance of IgG (P = 0.046), a reduction in 24-h systolic blood pressure of 10 mmHg (2-18) (P = 0.019) (mean +/- +/- SE) from 148 +/- 3 to 138 +/- 5 mmHg, and a mean reduction in GFR of 5 ml. min(-1). 1.73 m(-2) (0.1-9) (P = 0.045). CONCLUSIONS: Dual blockade of the RAS reduces albuminuria and blood pressure in type 2 diabetic patients with DN responding insufficiently to previous antihypertensive therapy, including ACE inhibitors in recommended doses. PMID- 11772909 TI - Carriers of an inactivating beta-cell ATP-sensitive K(+) channel mutation have normal glucose tolerance and insulin sensitivity and appropriate insulin secretion. AB - OBJECTIVE: Insulin release from the pancreatic beta-cells is controlled by ATP sensitive K(+) (K(ATP)) channels, which consist of a hetero-octameric complex of four sulfonylurea receptor 1 (SUR1) and four Kir6.2 proteins. Mutations in the SUR1 gene are the major cause of congenital hyperinsulinemia (CHI). Despite the hereditary nature of CHI, studies of glucose homeostasis in heterozygous relatives of CHI patients are lacking. Theoretically, in the heterozygous state of the SUR1 gene mutation, only 1 of 16 K(ATP) channels consists of entirely normal subunits. The aim of our study was to investigate in vivo the glucose homeostasis of heterozygous SUR1 mutation carriers. RESEARCH DESIGN AND METHODS: We studied 8 parents of CHI patients, all 8 of whom were heterozygous for the inactivating SUR1 mutation V187D, and 10 matched control subjects. We evaluated glucose tolerance and insulin secretory capacity with oral and intravenous glucose tests, rates of whole-body glucose uptake with hyperinsulinemic euglycemic clamps, C-peptide response to hypoglycemia during hyperinsulinemic hypoglycemic clamp, and function of the K(ATP) channels with intravenous tolbutamide test. RESULTS: Carriers of the V187D substitution had normal glucose tolerance, normal tissue sensitivity to insulin, and no signs of inappropriate insulin secretion. The normal insulin response to tolbutamide indicated that heterozygosity for the V187D mutation did not impair K(ATP) channel function. CONCLUSIONS: We conclude that the heterozygous carriers of the SUR1 mutation had normal glucose metabolism and insulin secretion, indicating that carriers of recessive K(ATP) channel mutations are unlikely to be at an increased risk of hypoglycemia or other disturbances in glucose metabolism. PMID- 11772910 TI - The sulfonylurea glyburide induces impairment of glucagon and growth hormone responses during mild insulin-induced hypoglycemia. AB - OBJECTIVE: The sulfonylurea (SU) glyburide may cause severe and prolonged episodes of hypoglycemia. We aimed at investigating the impact of glyburide on glucose counterregulatory hormones during stepwise hypoglycemic clamp studies. RESEARCH DESIGN AND METHODS: We performed stepwise hypoglycemic clamp studies in 16 healthy volunteers (7 women and 9 men aged 44 +/- 10 years). We investigated counterregulatory hormonal and symptom responses at arterialized venous plasma glucose levels (PG) of 3.8, 3.2, and 2.6 mmol/l, comparing 10 mg glyburide orally and placebo in a double-blind, randomized crossover fashion. RESULTS: The increase in plasma glucagon with time from PG = 3.8 onward was smaller for glyburide than for placebo (P = 0.014). Plasma glucagon area under the curve (AUC)(60-180) was lower after glyburide than after placebo (1,774 +/- 715 vs. 2,161 +/- 856 pmol. l(-1). min, P = 0.014). From PG = 3.8 onward, plasma growth hormone (GH) levels with placebo were nearly two times (1.9 [95% CI 1.2-2.9]) as high as with glyburide (P = 0.011). AUC(60-180) for GH was lower after glyburide than after placebo (geometric mean [range] 665 [356-1,275] and 1,058 [392-1,818] mU. l(-1). min, respectively; P = 0.04). No significant differences were observed for plasma cortisol, epinephrine and norepinephrine, or incremental symptom scores. CONCLUSIONS: The SU glyburide induces multiple defects in glucose counterregulatory hormonal responses, notably decreases in both glucagon and GH release. PMID- 11772911 TI - Peripheral artery disease, diabetes, and reduced lower extremity functioning. AB - OBJECTIVE: To characterize lower extremity function and dysfunction in peripheral artery disease (PAD) patients with and without diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 460 men and women with PAD (147 with diabetes) were recruited from three academic medical centers. Assessments included ankle brachial index (ABI), neuropathy score, 6-min walk distance, 4-m walking velocity, Walking Impairment Questionnaire (0-100 scale, 100 = best), and summary performance score (SPS) (0-12 scale, 12 = best). RESULTS: The mean ABI was similar in PAD patients with and without diabetes. PAD patients with diabetes were younger, had a higher BMI, had a worse neuropathy score, and had a greater number of cardiovascular comorbidities compared with those without diabetes. Participants with diabetes were less likely to report classical symptoms of intermittent claudication and more likely to report exertional leg pain, which sometimes started at rest. After adjusting for age, those with diabetes had a shorter mean 6-min walk distance (1,040 vs. 1,168 feet, P < 0.001), slower fast pace 4-m walk velocity (0.83 vs. 0.90 m/sec, P < 0.001), and a lower SPS (7.3 vs. 8.6, P < 0.001) than those without diabetes. Patients with diet-controlled diabetes performed better than those on diabetes medications. Differences in lower extremity functioning between patients with and without diabetes were largely attenuated but not abolished for SPS and fast-pace 4-m walk velocity after adjustment for type of exertional leg pain, neuropathy score, and number of cardiovascular comorbidities. CONCLUSIONS: Subjects with PAD and diabetes have poorer lower extremity function than those with PAD alone. This difference in functioning appears to be largely explained by diabetes-associated neuropathy, differences in exertional leg symptoms, and greater cardiovascular disease in patients with diabetes. PMID- 11772912 TI - "Diabetic mastopathy," or sclerosing lymphocytic lobulitis, is strongly associated with type 1 diabetes. AB - OBJECTIVE: To demonstrate the strong association of diabetic mastopathy or sclerosing lymphocytic lobulitis with type 1 diabetes mellitus by studying appropriate control groups and to describe risk factors and natural history of the disorder. RESEARCH DESIGN AND METHODS: This was a retrospective cross sectional study of four groups of patients conducted at a setting tertiary care medical center. We examined benign breast biopsies (investigator masked to identity) from age-matched patients with types 1 and 2 diabetes, autoimmune thyroid disease, or none of the above disorders for sclerosing lymphocytic lobulitis. Several risk factors proposed for the disorder (age at diagnosis of benign breast disease, duration of diabetes, age at onset of diabetes, prevalence of retinopathy, neuropathy, nephropathy and cheiroarthropathy, glycemic control, parity, oral contraceptive use, menopausal status, or number of breast biopsies) were evaluated, and patients were contacted to describe the natural history of the disorder. RESULTS: Sclerosing lymphocytic lobulitis was identified in 69.7% of the subjects with type 1 diabetes and 1.8% of those with autoimmune thyroid disease diagnosed with benign breast disease at surgery. It did not occur in patients with type 2 diabetes with or without insulin treatment or in control subjects. Only retinopathy and peripheral neuropathy were associated with sclerosing lymphocytic lobulitis. Breast carcinoma or lymphoma did not occur subsequently in any type 1 diabetes patient with or without sclerosing lymphocytic lobulitis. CONCLUSIONS: Sclerosing lymphocytic lobulitis is strongly associated with type 1 diabetes. Retinopathy and neuropathy are associated with the disorder. The risk of malignancy is not increased. PMID- 11772913 TI - Hormone replacement therapy, insulin sensitivity, and abdominal obesity in postmenopausal women. AB - OBJECTIVE: The purpose of this study was to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total and/or abdominal adiposity and fat deposition in the muscle. RESEARCH DESIGN AND METHODS: We studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age (57 +/- 3 vs. 58 +/- 2 years), weight (87.9 +/- 6.0 vs. 83.0 +/- 3.9 kg), and BMI (33.9 +/- 1.7 vs. 33.9 +/- 1.9 kg/m(2)) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age (59 +/- 2 vs. 60 +/- 2 years), weight (82.8 +/- 3.7 vs. 83.7 +/- 4.1 kg), and BMI (30.7 +/- 1.0 vs. 29.9 +/- 1.3 kg/m(2)). RESULTS: VO(2max) (maximal aerobic capacity), percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid-thigh low-density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured during the last 30 min of a 3-h hyperinsulinemic-euglycemic clamp (40 mU. m(2). min(-1)). Postmenopausal women taking oral estrogen had a 31% lower M than women not on HRT (42.7 +/- 4.0 vs. 61.7 +/- 4.7 micromol. kg(FFM). min(-1), P < 0.05). M was 26% lower in women taking estrogen plus progesterone (44.0 +/- 3.5 vs. 59.7 +/- 6.2 micromol. kg(FFM). min(-1), P < 0.05) than women not on HRT. M/I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36% lower in women taking estrogen compared with matched women not on HRT (P < 0.05) and 28% lower in women taking estrogen plus progesterone compared with matched women not on HRT (P < 0.05). CONCLUSIONS: Postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity. PMID- 11772914 TI - The treatment of hypertension in adult patients with diabetes. PMID- 11772915 TI - Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. PMID- 11772916 TI - Treatment of hypertension in adults with diabetes. PMID- 11772917 TI - Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. PMID- 11772918 TI - Standards of medical care for patients with diabetes mellitus. PMID- 11772920 TI - Dancing with many different ghosts: treatment of youth with type 2 diabetes. PMID- 11772919 TI - Treatment issues in type 1 diabetes. PMID- 11772921 TI - The effect of Ipomoea batatas (Caiapo) on glucose metabolism and serum cholesterol in patients with type 2 diabetes: a randomized study. PMID- 11772922 TI - Tissue polypeptide-specific antigen serum concentrations in children, adolescents, and young adults with type 1 diabetes. PMID- 11772923 TI - The effect of Qi-gong relaxation exercise on the control of type 2 diabetes mellitus: a randomized controlled trial. PMID- 11772924 TI - Leukocytoclastic vasculitis induced by subcutaneous injection of human insulin in a patient with type 1 diabetes and essential thrombocytemia. PMID- 11772925 TI - Smoking and microalbuminuria: a case-control study in African-Americans with type 2 diabetes. PMID- 11772926 TI - Frequency of blood glucose monitoring in relation to glycemic control in patients with type 2 diabetes. PMID- 11772927 TI - The healthy women bias and hormone replacement therapy in women with type 2 diabetes. PMID- 11772929 TI - Potential pharmacokinetics interference between alpha-glucosidase inhibitors and other oral antidiabetic agents. PMID- 11772930 TI - Science and the fight against bioterrorism. PMID- 11772931 TI - Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents. AB - The potential to block tumor growth by inhibition of the neoangiogenic process represents an intriguing approach to the treatment of solid tumors. The high proliferation rate in the tumor deprived of proper vascularization would be balanced by cell death due to lack of diffusion of nutrients and oxygen. Matrix metalloproteinases (MMPs), angiogenic growth factors, and their receptors are the main targets of an increasing number of clinical trials approved to test the tolerance and therapeutic efficacy of antiangiogenic agents. We observed that a series of substances proposed as possible cancer chemopreventive agents show antiangiogenic properties when tested in in vitro and in vivo angiogenesis models. We demonstrated that N-acetyl-l-cysteine is able to reduce the invasive and metastatic potential of melanoma cells, and to inhibit endothelial cell invasion by direct inhibition of MMP activity. We also showed that epigallocatechin gallate (EGCG), a flavonoid from green tea that possesses chemopreventive activity in experimental and epidemiological studies, is a potent inhibitor of MMP-2 and MMP-9. Angiogenesis has also been demonstrated to be a target for nonsteroidal anti-inflammatory drug chemopreventive activity. Based on these data, we hypothesize that other chemopreventive agents, including natural or synthetic retinoids, steroid hormone antagonists, peroxisome proliferator activated receptor gamma ligands, vitamin D, and protease inhibitors, might have antiangiogenesis as an important mechanism of action, a novel concept we will term 'angioprevention'. We analyze the mechanisms on how and why chemopreventive agents could exert antiangiogenic effects aimed at controlling tumor growth, and their potential use in the clinic. PMID- 11772932 TI - S-Adenosylmethionine: a control switch that regulates liver function. AB - Genome sequence analysis reveals that all organisms synthesize S adenosylmethionine (AdoMet) and that a large fraction of all genes is AdoMet dependent methyltransferases. AdoMet-dependent methylation has been shown to be central to many biological processes. Up to 85% of all methylation reactions and as much as 48% of methionine metabolism occur in the liver, which indicates the crucial importance of this organ in the regulation of blood methionine. Of the two mammalian genes (MAT1A, MAT2A) that encode methionine adenosyltransferase (MAT, the enzyme that makes AdoMet), MAT1A is specifically expressed in adult liver. It now appears that growth factors, cytokines, and hormones regulate liver MAT mRNA levels and enzyme activity and that AdoMet should not be viewed only as an intermediate metabolite in methionine catabolism, but also as an intracellular control switch that regulates essential hepatic functions such as regeneration, differentiation, and the sensitivity of this organ to injury. The aim of this review is to integrate these recent findings linking AdoMet with liver growth, differentiation, and injury into a comprehensive model. With the availability of AdoMet as a nutritional supplement and evidence of its beneficial role in various liver diseases, this review offers insight into its mechanism of action. PMID- 11772933 TI - Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. AB - Prolonged exposure of the brain to ethanol is a prerequisite for developing ethanol dependence, but the underlying neural adaptations are unknown. Here we demonstrate that rats subjected to repeated cycles of intoxication and withdrawal develop a marked and long-lasting increase in voluntary ethanol intake. Exposure induced but not spontaneous alcohol intake is antagonized by acamprosate, a compound clinically effective in human alcoholism. Expression analysis of cingulate cortex and amygdala reveals a set of long-term up-regulated transcripts in this model. These include members of pathways previously implicated in alcohol dependence (glutamatergic, endocannabinoid, and monoaminergic neurotransmission), as well as pathways not previously thought to be involved in this disorder (e.g., members of the mitogen-activated protein kinase pathway). Thus, alternating periods of ethanol intoxication and withdrawal are sufficient to induce an altered functional brain state, which is likely to be encoded by long-term changes in gene expression. These observations may have important implications for how alcoholism is managed clinically. Novel clinically effective treatments may be possible to develop by targeting the products of genes found to be regulated in our model. PMID- 11772934 TI - Prereceptor regulation of glucocorticoid action by 11beta-hydroxysteroid dehydrogenase: a novel determinant of cell proliferation. AB - Isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) act at a prereceptor level to regulate the tissue-specific availability of active glucocorticoids. To examine the effect of this on cell proliferation and differentiation, we have developed transfectant variants of a rat osteosarcoma cell line that express cDNA for 11beta-HSD1 (ROS 17/2.8beta1) or 11beta-HSD2 (ROS 17/2.8beta2). ROS 17/2.8beta1 showed net conversion of cortisone to cortisol whereas ROS 17/2.8beta2 showed only inactivation of cortisol to cortisone. There was no significant difference in glucocorticoid receptor (GR) expression between the different clones. However, in proliferation and differentiation studies, ROS 17/2.8beta2 cells were completely resistant to cortisol. In contrast, ROS 17/2.8beta1 were sensitive to both cortisone and cortisol. Expression of 11beta HSD1 decreased cell proliferation whereas 11beta-HSD2 increased proliferation. These responses appear to be due to metabolism of endogenous serum glucocorticoids; proliferation of ROS 17/2.8beta1 decreased further with exogenous cortisone or cortisol whereas ROS 17/2.8beta2 were resistant to both compounds. The pro-proliferative effects of 11beta-HSD2 were abrogated by 18beta glycyrrhetinic acid, an 11beta-HSD inhibitor, and in cells transfected with cDNA encoding inactive 11beta-HSD2. Data indicate that differential regulation of 11beta-HSD1 and 2 (rather than GR expression) is a key determinant of cell proliferation. Dysregulated expression of 11beta-HSD2 may be a novel feature of tumorigenesis. PMID- 11772935 TI - Sunlight-induced DNA damage in human mononuclear cells. AB - In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single-cell gel electrophoresis. The level of DNA damage was influenced by the average daily influx of sunlight < 50 days prior to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individual's background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could not be detected. Our results suggest that sunlight penetrates the outer layer of the human epidermis and damages the DNA in mononuclear cells circulating in the vessels of the skin. PMID- 11772936 TI - Cells in human postmortem brain tissue slices remain alive for several weeks in culture. AB - Animal models for human neurological and psychiatric diseases only partially mimic the underlying pathogenic processes. Therefore, we investigated the potential use of cultured postmortem brain tissue from adult neurological patients and controls. The present study shows that human brain tissue slices obtained by autopsy within 8 h after death can be maintained in vitro for extended periods (up to 78 days) and can be manipulated experimentally. We report for the first time that 1) neurons and glia in such cultures could be induced to express the reporter gene LacZ after transduction with adeno-associated viral vectors and 2) cytochrome oxidase activity could be enhanced by the addition of pyruvate to the medium. These slice cultures offer new opportunities to study the cellular and molecular mechanisms of neurological and psychiatric diseases and new therapeutic strategies. PMID- 11772937 TI - Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. AB - Glucocorticoids continue to be the major immunomodulatory agents used in clinical medicine today. However, their actions as anti-inflammatory and immunosuppressive drugs are both beneficial and deleterious. We analyzed the effect of glucocorticoids on the gene expression profile of peripheral blood mononuclear cells from healthy donors. DNA microarray analysis combined with quantitative TaqMan PCR and flow cytometry revealed that glucocorticoids induced the expression of chemokine, cytokine, and complement family members as well as of newly discovered innate immune-related genes, including scavenger and Toll-like receptors. In contrast, glucocorticoids repressed the expression of adaptive immune-related genes. Simultaneous inhibitory and stimulatory effects of glucocorticoids were found on inflammatory T helper subsets and apoptosis-related gene clusters. In cells activated by T cell receptor cross-linking, glucocorticoids down-regulated the expression of specific genes that were previously up-regulated in resting cells, suggesting a potential new mechanism by which they exert positive and negative effects. Considering the broad and continuously renewed interest in glucocorticoid therapy, the profiles we describe here will be useful in designing more specific and efficient treatment strategies. PMID- 11772938 TI - Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior. AB - We hypothesize that actin polymerization within vascular smooth muscle (VSM) in response to increased intravascular pressure is a novel and previously unrecognized mechanism underlying arterial myogenic behavior. This hypothesis is based on the following observations. 1) Unlike skeletal or cardiac muscle, VSM contains a substantial pool of unpolymerized globular (G) actin whose function is not known. 2) The cytosolic concentration of G-actin is significantly reduced by an elevation in intravascular pressure, demonstrating the dynamic nature of actin within VSM and implying a shift in the F:G equilibrium in favor of F-actin. 3) Agents that inhibit actin polymerization and stabilize the cytoskeleton (cytochalasins and latrunculin) inhibit the development of myogenic tone and decrease the effectiveness of myogenic reactivity. 4) Depolymerization of F-actin with cytochalasin D causes VSM relaxation and increased G-actin content, whereas polymerization of F-actin with jasplakinolide causes VSM contraction and decreased G-actin content. These results are consistent with observations in other cell types in which actin dynamics have been implicated in contractility and/or motility. Actin filament formation in VSM may therefore underlie mechanotransduction and, by providing additional sites for interaction with myosin, enhance force production in response to pressure. Although the mechanism by which actin polymerization is stimulated by pressure is not known, it likely occurs via integrin-mediated activation of signal transduction pathways previously associated with VSM contraction (e.g., PKC activation, Rho A, and tyrosine phosphorylation). PMID- 11772939 TI - A possible role for pi-stacking in the self-assembly of amyloid fibrils. AB - Amyloid fibril formation is assumed to be the molecular basis for a variety of diseases of unrelated origin. Despite its fundamental clinical importance, the mechanism of amyloid formation is not fully understood. When we analyzed a variety of short functional fragments from unrelated amyloid-forming proteins, a remarkable occurrence of aromatic residues was observed. The finding of aromatic residues in diverse fragments raises the possibility that pi-pi interactions may play a significant role in the molecular recognition and self-assembly processes that lead to amyloid formation. This is in line with the well-known central role of pi-stacking interactions in self-assembly processes in the fields of chemistry and biochemistry. We speculate that the stacking interactions may provide energetic contribution as well as order and directionality in the self-assembly of amyloid structures. Experimental data regarding amyloid formation and inhibition by short peptide analogs also support our hypothesis. The pi-stacking hypothesis suggests a new approach to understanding the self-assembly mechanism that governs amyloid formation and indicates possible ways to control this process. PMID- 11772940 TI - Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. AB - Although abnormal cell growth in arterial vessel walls underpins vascular remodeling in high blood pressure, the molecular basis of the abnormality in hypertension has not been fully defined. Here, we report that in the aorta of spontaneously hypertensive rats, telomerase is selectively activated and telomeres are lengthened, in vivo and in vitro. Down-regulation of telomerase, the ribonucleoprotein complex responsible for the maintenance and elongation of telomeres (the ends of chromosomes) arrests the increased proliferation of spontaneously hypertensive rat vascular smooth muscle cells and induces apoptosis. This apoptosis is reversible by overexpressing telomerase and is prevented by increasing p53 tumor suppressor protein expression and worsened by lowering p53. Telomerase activation, telomere maintenance, and the p53 checkpoint appear to be critical for increased vascular smooth muscle proliferation, thus they represent potential novel therapeutic targets in hypertension. PMID- 11772941 TI - The voltage-independent B-type Ca2+ channel modulates apoptosis of cardiac myocytes. AB - In cardiac myocytes, Ca2+ is the second messenger of various physiological processes, including the excitation-contraction coupling phenomenon. Here, we examined how Ca2+ regulates cardiac myocyte apoptosis. Using an adult rat ventricular myocyte culture model, we found that ceramide (Cer) induces an apoptotic process that is highly sensitive to calcium: it is inhibited by the Ca2+buffer BAPTA-AM and is potentiated by the Ca2+ ionophore ionomycin. Cer treated myocytes maintained their Ca2+ homeostasis and normal activity of their voltage-dependent sarcolemmal Ca2+ entry pathways but showed enhanced activity of B-type Ca2+ channels that were stimulated by Cer in the inside-out patch clamp configuration. Pharmacological modulations of B-type Ca2+ channels modulated Cer induced apoptosis. Mitochondria were involved in Cer-induced apoptosis, as indicated by the inhibitory effect of cyclosporine A and caspase-9 inhibitor. Both the loss of mitochondrial membrane potential and the caspase-9 activation in Cer-treated myocytes were attenuated by blocking B-type Ca2+ channels. The mitochondrial Ca2+ content was evaluated as changes in [Ca2+]i after a short application of a mitochondrial uncoupler, FCCP, was increased in Cer-treated cells. Together, these results show that Ca2+ modulates Cer-induced cardiac myocyte apoptosis through the coupling of B-type Ca2+ channels with mitochondria. PMID- 11772942 TI - Selection of phage-displayed llama single-domain antibodies that transmigrate across human blood-brain barrier endothelium. AB - Delivery to the brain of drugs, peptides, and genes depends on the availability of brain-specific delivery vectors. We used a phage-displayed library of llama single-domain antibodies (sdAbs) to enrich for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). Two sdAbs (FC5 and FC44) were selected, sequenced, subcloned, and expressed as fusion proteins with c-Myc-His5 tags. Similar to phage-displayed sdAbs, soluble FC5 and FC44 were shown to selectively bind HCEC and to transmigrate across an in vitro human blood-brain barrier (BBB) model. Both FC5 and FC44, in contrast to an unrelated llama sdAb, were also detected in the brain after i.v. injection into mice. These small (approximately 14 kDa) antibodies have characteristics essential for a carrier-vector and can be used to facilitate drug transport across the BBB. PMID- 11772943 TI - Aldose reductase activation is a key component of myocardial response to ischemia. AB - Aldose reductase, a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications in diabetes. Despite recent studies from our laboratory demonstrating protection of ischemic hearts by an aldose reductase inhibitor, the presence and influence of aldose reductase in cardiac tissue remain unknown. Our goal in this study was to isolate and characterize the kinetic properties of cardiac aldose reductase, as well as to study the impact of flux via this enzyme on glucose metabolism and contractile function in hearts subjected to ischemia-reperfusion. Results demonstrate that ischemia increases myocardial aldose reductase activity and that these increases are, in part, due to activation by nitric oxide. The kinetic parameter of cardiac aldose reductase (Kcat) was significantly higher in ischemic tissues. Aldose reductase inhibition increased glycolysis and glucose oxidation. Aldose reductase inhibited hearts, when subjected to ischemia/reperfusion, exhibited less ischemic injury and was associated with lower lactate/pyruvate ratios (a measure of cytosolic NADH/NAD+), greater tissue content of adenosine triphosphate, and improved cardiac function. These findings indicate that aldose reductase is a component of ischemic injury and that pharmacological inhibitors of aldose reductase present a novel adjunctive approach for protecting ischemic hearts. PMID- 11772944 TI - Functional analysis of discoidin domain receptor 1: effect of adhesion on DDR1 phosphorylation. AB - Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase (RTK), has been shown to be activated mainly by soluble fibrillar collagen. Unusually, the kinetics of phosphorylation of the receptor is slow, with maximal phosphorylation observed after 90 min. To understand the reasons for slow phosphorylation of the receptor, we examined several cell lines under different conditions. We confirm that endogenous DDR1 is phosphorylated slowly by collagen in adherent T47D and HCT116 cells. In detached and resuspended cells, collagen induced rapid phosphorylation of DDR1. This was further confirmed with a semiadherent cell line (COLO201) and one that grows as a suspension (K562), both of which express endogenous DDR1. Replating K562 on fibronectin to mimic adherent conditions altered the kinetics of phosphorylation from rapid to slow, similar to those of adherent cells. The slow kinetics of phosphorylation in the adherent state was probably not due to cell-cell contacts because EDTA had no major effect. However, pervanadate in the absence of collagen was able to induce strong DDR1 phosphorylation, indicating that a phosphatase may inhibit or delay the phosphorylation of DDR1. Further, downstream signals after phosphorylation of DDR1 by collagen were not transmitted through the classical mitogen-activated protein kinase pathway. In addition, a chimeric TrkA-DDR1 receptor failed to become phosphorylated on stimulation with nerve growth factor (NGF), although it dimerized normally. This is the first RTK whose kinetics of phosphorylation is dependent on cellular context. The interaction of the cells with the matrix, rather than cell-cell contact, is probably responsible for the inhibition of phosphorylation. PMID- 11772945 TI - Antiangiogenic activity of aeroplysinin-1, a brominated compound isolated from a marine sponge. AB - (+)-aeroplysinin-1, an antibacterial brominated compound produced by certain sponges, was selected during a blind high-throughput screening for new potential antiangiogenic compounds obtained from marine organisms. In a variety of experimental systems, representing the sequential events of the angiogenic process, aeroplysinin-1 treatment of endothelial cells resulted in strong inhibitory effects. Aeroplysinin-1 inhibited the growth of endothelial cells in culture and induced endothelial cell apoptosis. Capillary tube formation on Matrigel was completely abrogated by addition of aeroplysinin-1 at the low micromolar range. Aeroplysinin-1 also exhibited a clear inhibitory effect on the migration capabilities of endothelial cells. Zymographic assays showed that aeroplysinin-1 treatment produced a decrease in the concentration of matrix metalloproteinase-2 and urokinase in conditioned medium from endothelial cells. Finally, aeroplysinin-1 exhibited a dose-dependent inhibitory effect on the in vivo chorioallantoic membrane assay, showing potent apoptosis-inducing activity in the developing endothelium. The in vivo inhibition of angiogenesis by aeroplysinin-1 was confirmed by the Matrigel plug assay. Together, our data indicate that aeroplysinin-1 is a compound that interferes with key events in angiogenesis, making it a promising drug for further evaluation in the treatment of angiogenesis-related pathologies. PMID- 11772946 TI - Astrocyte Ca2+ waves trigger responses in microglial cells in brain slices. AB - Pathologic impacts in the brain lead to a widespread activation of microglial cells far beyond the site of injury. Here, we demonstrate that glial Ca2+ waves can trigger responses in microglial cells. We elicited Ca2+ waves in corpus callosum glial cells by electrical stimulation or local adenosine triphosphate (ATP) ejection in acute brain slices. Macroglial cells, but not microglia, were bulk-loaded with Ca2+-sensitive dyes. Using a transgenic animal in which astrocytes were labeled by the enhanced green fluorescence protein (EGFP) allowed us to identify the reacting cell populations: the wave activated a Ca2+ response in both astrocytes and non-astrocytic glial cells and spread over hundreds of micrometers even into the adjacent cortical and ventricular cell layers. Regenerative ATP release and subsequent activation of metabotropic purinergic receptors caused the propagation of the glial Ca2+ wave: the wave was blocked by the purinergic receptor antagonist Reactive Blue 2 and was not affected by the gap junction blocker octanol, but enhanced in Ca2+ free saline. To test whether microglial cells respond to the wave, microglial cells were labeled with a dye coupled lectin and membrane currents were recorded with the patch-clamp technique. When the wave passed by, a current with the characteristics of a purinergic response was activated. Thus, Ca2+ waves in situ are not restricted to astrocytic cells, but broadly activate different glial cell types. PMID- 11772947 TI - von Hippel Lindau tumor suppressor and HIF-1alpha: new targets of NSAIDs inhibition of hypoxia-induced angiogenesis. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin synthesis and impair healing of gastrointestinal ulcers and growth of colonic tumors, in part, by inhibiting angiogenesis. The mechanisms of this inhibition are incompletely explained. Here we demonstrate that both nonselective (indomethacin) and COX-2 selective (NS-398) NSAIDs inhibit hypoxia-induced in vitro angiogenesis in gastric microvascular endothelial cells via coordinated sequential events: 1) increased expression of the von Hippel-Lindau (VHL) tumor suppressor, which targets proteins for ubiquitination leading to 2) reduced accumulation of hypoxia inducible factor-1alpha (HIF-1alpha) and, as a result, 3) reduced expression of vascular endothelial growth factor (VEGF) and its specific receptor Flt-1. Because HIF-1alpha is the major trigger for hypoxia-induced activation of the VEGF and Flt-1 genes, this could explain how NSAIDs inhibit hypoxia-induced angiogenesis. Exogenous VEGF and, to a lesser extent, exogenous prostaglandins partly reversed the NSAIDs inhibition of hypoxia-induced angiogenesis. Taken together, these results indicate that NSAIDs inhibit hypoxia-induced angiogenesis in endothelial cells by inhibiting VEGF and Flt-1 expression through increased VHL expression and the resulting ubiquitination and degradation of HIF-1alpha. This action of NSAIDs has both prostaglandin-dependent and prostaglandin independent components. PMID- 11772948 TI - Microencapsulated iNOS-expressing cells cause tumor suppression in mice. AB - Macrophages can kill tumor cells by releasing high levels of nitric oxide (NO) and related reactive nitrogen species such as nitroxyl and peroxynitrite, after up-regulation of expression of the inducible nitric oxide synthase gene (iNOS). In this paper we describe two novel human cell lines that are capable of expressing high levels of iNOS under the control of analogues of either the insect hormone ecdysone or tetracycline. We have entrapped these iNOS-expressing cells within a semipermeable alginate-poly-L-lysine membrane as a means of delivery to tumor sites in a nude mouse model. These encapsulated cells can be induced to generate sustainable high concentrations NO and reactive nitrogen species at tumor sites after treatment either with ponasterone A or muristerone A or with doxycycline. Delivery of these iNOS-expressing cells to tumors formed from human ovarian cancer SKOV-3 cells results in 100% killing, whereas treatment of tumors formed from human colon cancer DLD-1 cells results in 54% killing. We show that in these iNOS-expressing cells, tumor killing is associated with concomitant up-regulation of the Fas/FasL proteins. PMID- 11772949 TI - Differential gene expression in premalignant human epidermis revealed by cluster analysis of serial analysis of gene expression (SAGE) libraries. AB - Serial analysis of gene expression (SAGE) has been used for quantitative analysis of gene expression. We applied cluster analysis on multiple SAGE libraries derived from premalignant epidermal tissue (actinic keratosis), normal human epidermis, and cultured keratinocytes. The samples were obtained from skin biopsies without contamination by dermal tissue or blood. A total of 60,000 transcripts (tags) were analyzed. Two-way cluster analysis was applied to both the transcripts and the tissues, resulting in separation of the cultured cells from the epidermal samples, and clustering of many, presumably coregulated, genes. Two clusters of genes, strongly up-regulated in the tumor tissue compared with normal epidermis, were investigated in more detail. The differential expression of genes could be confirmed in actinic keratosis from four patients. Several of these genes have been previously associated with carcinogenesis or are likely to be important on the basis of their presumed function. Automated literature search tools show that a subgroup of these genes is coexpressed in other tissues and is part of an epidermal differentiation gene cluster on chromosome 1q21. We conclude that cluster analysis on large data sets uncovers clear partitions and correlations that could be confirmed by independent methods. We predict that these partitions will lead to biological interpretations that can be relevant for understanding the processes of carcinogenesis and tumor progression. PMID- 11772950 TI - Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation. AB - Angiostatin effectively blocks tumor angiogenesis through still poorly understood mechanisms. Given the close association between immune and vascular regulation, we investigated the effects of angiostatin on angiogenesis-associated leukocytes. Angiostatin inhibited the migration of monocytes and, even more markedly, neutrophils. Angiostatin blocked chemotaxis of neutrophils to CXCR2 chemokine receptor agonists (IL-8, MIP-2, and GROalpha), formyl-Met-Leu-Phe (fMLP), and 12 O-tetradecanoylphorbol 13-acetate, and repressed fMLP-induced mitochondrial activity. Two different angiostatin forms (kringles 1-4 and 1-3) were effective, whereas whole plasminogen had no effect. IL-8, MIP-2, and GROalpha induced intense angiogenic reactions in vivo, but no angiogenic response to these factors was observed in neutropenic mice, demonstrating an essential role for neutrophils. Angiostatin potently inhibited chemokine-induced angiogenesis in vivo, and consistent with in vitro observations, both angiostatin forms were active and whole plasminogen had little effect. Angiostatin inhibition of angiogenesis in vivo was accompanied by a striking reduction in the number of recruited leukocytes. In vivo, the inflammatory agent lipopolysaccharide also induced extensive leukocyte infiltration and angiogenesis that were blocked by angiostatin. Neutrophils expressed mRNAs for ATP synthase and angiomotin, two known angiostatin receptors. These data show that angiostatin directly inhibits neutrophil migration and neutrophil-mediated angiogenesis and indicate that angiostatin might inhibit inflammation. PMID- 11772951 TI - Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women. AB - Functional foods enriched with plant stanols lower atherogenic LDL cholesterol concentrations. This effect is caused at least partly by a decreased intestinal cholesterol absorption. It has been suggested that LDL production is reduced after plant stanol consumption, but it is unknown whether LDL receptor expression is affected and contributes to the LDL-lowering effect of plant stanols. Markers for endogenous cholesterol synthesis (lathosterol) increase, but it is not known how this higher cholesterol synthesis is regulated at the molecular level. In a double-blind placebo controlled trial, we have found that compared with the control group (N=15), daily consumption of 3.8-4.0 g plant stanol esters (N=29) for 8 weeks increased LDL receptor mRNA levels in human mononuclear blood cells by 43% (P=0.003). LDL receptor protein concentrations on the surface of monocytes and T lymphocytes increased by 37% (P=0.003) and 25% (P=0.013), suggesting an increased translation. This increased protein expression appeared to be functional, since changes in serum LDL cholesterol correlated negatively with changes in LDL receptor mRNA levels (r=-0.361; P=0.015) and changes in LDL receptor protein expression in monocytes (r=-0.440; P<0.001) and T lymphocytes (r=-0.307; P=0.018). Based on these results, we suggest that the higher LDL receptor expression contributed to a lowered LDL formation along the apoB cascade. Whole body cholesterol synthesis increased, as indicated by the rise in serum cholesterol-standardized lathosterol concentrations, but the 34% increased HMG-CoA reductase mRNA concentrations did not reach statistical significance. Nor did it correlate significantly with changes in serum cholesterol-standardized lathosterol concentrations. This suggests that HMG-CoA reductase may be only partly regulated at a transcriptional level. PMID- 11772952 TI - Cell differentiation by mechanical stress. AB - Growth factors, hormones, and other regulatory molecules are traditionally required in tissue engineering studies to direct the differentiation of progenitor cells along specific lineages. We demonstrate that mechanical stimulation in vitro, without ligament-selective exogenous growth and differentiation factors, induces the differentiation of mesenchymal progenitor cells from the bone marrow into a ligament cell lineage in preference to alternative paths (i.e., bone or cartilage cell lineages). A bioreactor was designed to permit the controlled application of ligament-like multidimensional mechanical strains (translational and rotational strain) to the undifferentiated cells embedded in a collagen gel. The application of mechanical stress over a period of 21 days up-regulated ligament fibroblast markers, including collagen types I and III and tenascin-C, fostered statistically significant cell alignment and density and resulted in the formation of oriented collagen fibers, all features characteristic of ligament cells. At the same time, no up-regulation of bone or cartilage-specific cell markers was observed. PMID- 11772953 TI - Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. AB - Taurine is involved in cell volume homeostasis, antioxidant defense, protein stabilization, and stress responses. High levels of intracellular taurine are maintained by a Na+-dependent taurine transporter (TAUT) in the plasma membrane. In view of the immunomodulatory and cytoprotective effects of taurine, a mouse model with a disrupted gene coding for the taurine transporter (taut-/- mice) was generated. These mice show markedly decreased taurine levels in a variety of tissues, a reduced fertility, and loss of vision due to severe retinal degeneration. In particular, the retinal involvement identifies the taurine transporter as an important factor for the development and maintenance of normal retinal functions and morphology. PMID- 11772955 TI - Treatment of colorectal metastases: surgery, cryotherapy, or radiofrequency ablation. AB - The liver is the most common site of metastases from colorectal cancer. There has therefore been growing interest in how liver metastases may be ablated. The most common techniques for ablation of liver metastases are surgical resection, cryotherapy, and increasingly in recent years, radiofrequency ablation. PMID- 11772956 TI - Anti-relaxation therapy in GORD. PMID- 11772957 TI - Positive suggestions about the anti-HBc positive donor. PMID- 11772958 TI - Osteoporosis in patients with inflammatory bowel disease. PMID- 11772959 TI - The link between rotavirus vaccination and intussusception: implications for vaccine strategies. PMID- 11772960 TI - Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells. AB - BACKGROUND: Different acid and peptic related gastroduodenal diseases are associated with both increased gastric secretion and Helicobacter pylori infection. Patients with H pylori associated gastritis or duodenal ulcer have increased serum pepsinogen levels which decrease after eradication. The mechanisms of H pylori induced gastric mucosal damage are not completely understood. AIM: To determine the effects of H pylori on pepsinogen secretion from isolated human peptic cells. METHODS: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. H pylori was obtained from gastric biopsies (antrum and body), and cultured in non selective and selective media. Isolates of H pylori were used at different concentrations (1 - 20 x 10(6) colony forming units (cfu)). RESULTS: H pylori (10(6) - 2 x 10(7) cfu) increased basal pepsinogen secretion in a concentration dependent manner. This stimulus was not observed with Escherichia coli. The increased secretion was in addition to that observed with 0.1 mM histamine and 0.1 mM dibutyryl-cyclic adenosine monophosphate. However, H pylori did not affect either carbamylcholine (0.1-10 microM) or cholecystokinin (1 microM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor N(w) monomethyl-L-arginine (1 mM) inhibited H pylori induced cGMP generation and pepsinogen secretion, which were also reduced in the absence of extracellular calcium. H pylori induced pepsinogen secretion was not affected by the absence/presence of the cagA gene. CONCLUSIONS: H pylori increases pepsinogen secretion from human peptic cells through a calcium and nitric oxide mediated intracellular pathway. This effect is independent of the H pylori virulent cagA gene, and may be a mechanism of H pylori induced gastric mucosal damage. PMID- 11772961 TI - Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. AB - BACKGROUND AND AIMS: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. METHODS: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7 15.5)). CONCLUSIONS: In patients with reflux disease, the GABA(B) agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux disease. PMID- 11772963 TI - A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. AB - BACKGROUND: Three randomised trials have demonstrated reduction in mortality from colorectal cancer (CRC) by repeated screening with faecal occult blood tests, including the trial presented here, which is the only one still in progress. AIMS: To evaluate reduction in mortality after seven screening rounds and the possible influence of compliance on mortality from CRC. METHODS: At Funen in Denmark, random allocation to biennial screening with Hemoccult-II in 30 967 subjects aged 45-75 years and 30,966 controls was performed in 1985 from a population of 137,485 of the same age. Only participants who completed the first screening round were invited for further screening. Colonoscopy was offered if the test was positive. The primary end point was death from CRC, and the 10 year results were published in 1996. RESULTS: From the beginning of the first screening to the seventh round, mean age increased from 59.8 to 70.0 years in the screening and control groups, and the male/female ratio decreased from 0.92 to 0.81. Those who accepted screening were younger than non-responders. Positivity rates varied from 0.8% to 3.8%, the cumulative ratio of a positive test was 5.1% after seven rounds, and 4.8% of patients had at least one colonoscopy. Mortality from CRC was significantly less in the screening group (relative risk (RR) 0.82 (0.69-0.97)), and the reduction in mortality was most pronounced above the sigmoid colon. After seven rounds, RR was reduced to less than 0.70 compared with controls. Mortality rates from causes other than CRC did not differ. Non responders had a significantly increased risk of death from CRC compared with those who accepted the full programme. Subjects who accepted the first screening, but not subsequent ones, demonstrated a tendency towards increased risk. CONCLUSIONS: The persistent reduction in mortality from CRC in a biennial screening program with Hemoccult-II, and a reduction in RR to less than 0.70 in those adhering to the programme, support attempts to introduce larger scale population screening programmes. The smaller effect on mortality from CRC in the rectum and sigmoid colon suggests evaluation by additional flexible sigmoidoscopy with longer intervals. PMID- 11772962 TI - Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease. AB - BACKGROUND: Endoscopic recurrence after surgery in Crohn's disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1 beta, tumour necrosis factor alpha (TNF-alpha)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis. PATIENTS AND METHODS: We evaluated if ileal TNF-alpha, IL-1 beta, or IL 10 mRNA levels measured at the time of surgery predict endoscopic recurrence, and if ileal IL-10 levels are associated with particular IL-10 promoter alleles. Ileal biopsies were obtained peroperatively from the healthy neoileum of patients undergoing a right ileocolectomy for Crohn's disease. Mucosal TNF-alpha, IL-1 beta, and IL-10 mRNA levels were quantified by competitive polymerase chain reaction. A cut off value was determined using a receiver operating curve. IL 10.G promoter haplotypes were analysed using a polymorphic dinucleotide repeat in the IL-10 promoter region. RESULTS: Three months after surgery, 53% of patients had endoscopic recurrence while 47% remained free of disease. The risk of endoscopic recurrence correlated with ileal IL-10 mRNA concentrations (r(2)=0.81). Endoscopic recurrence occurred more frequently in patients classified as low IL-10 producers than in those that were high producers (80% v 40%) (p=0.02). Patients with at least one of the two alleles G7-8 or G10-13 produced, respectively, higher (p=0.006) and lower (p=0.029) ileal IL-10 mRNA. The distribution of IL-10.G microsatellite genotypes was similar in patients with or without endoscopic recurrence. CONCLUSION: Low ileal IL-10 mRNA concentration is a good marker of endoscopic recurrence in Crohn's disease but the distribution of IL-10.G haplotypes cannot predict the postoperative evolution of the disease. PMID- 11772964 TI - Protective effect of faecal occult blood test screening for colorectal cancer: worse prognosis for screening refusers. AB - BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) by faecal occult blood testing (FOBT) decreases CRC mortality by 15-33%. Compliance remains an obstacle to maximising the benefit of FOBT screening. We tested the hypothesis that individuals offered FOBT screening but refused would have an increased incidence and worse prognosis for CRC compared with those tested and with controls. METHODS: Annual screening was offered to 3548 average risk individuals, > or = 40 years of age, from a highly stable population. A total of 2538 agreed to testing (group 1) and 1010 (28%) refused (group 2). Another 1376 individuals were never offered the test and served as controls (group 3). The groups were followed for 11 years: a three year screening period (1985-1987) and an eight year follow up period at the end of the screening programme (1988-1995). Incidence, stage, and mortality were compared. Characterisation of refusers was completed in 188 and 130 subjects of groups 1 and 2, respectively. RESULTS: In the screening phase, mortality from CRC was significantly lower in group 1 than in groups 2 and 3. The cumulative incidence of CRC in the eight year follow up period was 21 (0.88%), 23 (2.28%), and 13 (0.94%) in groups 1, 2, and 3, respectively. This shows a reduction of 61.4% in group 1 compared with group 2 (relative risk 0.28 (95% confidence interval (CI) 0.19-0.32)) (p<0.001) and 6.4% compared with group 3 (relative risk 0.93 (95% CI 0.93-1.00)) (NS). During follow up, group 1 subjects also demonstrated a decrease in advanced Dukes' stage and mortality rate by 80% and 64%, and 79% and 62%, compared with groups 2 and 3, respectively. Refusers were more likely to be male, of Asian-African descent, and more likely to smoke, consume more coffee, and less tea or dairy foods. CONCLUSIONS: When accepted, FOBT may protect against CRC for prolonged periods. Individuals who refuse FOBT have a significantly higher CRC incidence and mortality rates than those who accept testing. PMID- 11772965 TI - Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study. AB - BACKGROUND AND AIMS: Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma. PATIENTS AND METHODS: Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI). RESULTS: After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)). CONCLUSION: In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer. PMID- 11772966 TI - Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients. AB - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome, characterised by familial aggregation of HNPCC related cancers, germline mutations in mismatch repair genes, and/or microsatellite instability (MSI) in tumour tissue. AIM: To estimate the frequency of HNPCC among non-selected Danish patients with colorectal cancer (CRC), and to evaluate the value of MSI analysis as a pre-screen test. METHODS: This was a prospective population based study on consecutive CRC patients. A family history of malignancy was obtained and suspected HNPCC cases were screened for hMLH1/hMSH2 mutations and subjected to MSI analysis. Patients with germline mutations and/or those with Amsterdam criteria I or II families were categorised as HNPCC patients. RESULTS: Among 1328 eligible CRC patients, 1200 (90.4%) completed a questionnaire. A total of 1.7% (95% confidence interval (CI) 1.0-2.4) (20 cases) were categorised as HNPCC patients. Amsterdam criteria I or II were met in 18 cases (1.5%), and in another two cases (0.2%) pathogenic hMLH1/hMSH2 mutations were detected without fulfillment of the Amsterdam criteria I or II. Among 77 patients younger than 50 years of age, 11 cases (14.3%) were categorised as HNPCC. The Amsterdam criteria I or II were met in eight of 10 gene carriers (80%). The MSI-high phenotype was demonstrated in all 10 gene carriers. CONCLUSION: The frequency of HNPCC was approximately 1.7% among all CRC cases and 14.3% among patients younger than 50 years of age. MSI analysis is a reliable pre screen test for hMLH1/hMSH2 mutations in families suspected of having HNPCC. PMID- 11772967 TI - Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. AB - BACKGROUND AND AIMS: Recently, novel somatostatin receptor (sstr) subtype specific ligand analogues have been developed for medical treatment of neuroendocrine tumours expressing different sstrs (sstr1-5). At present, individual expression patterns of sstr subtypes are based on methods such as in situ hybridisation and polymerase chain reaction at the transcriptional level. Therefore, we generated subtype specific antibodies against sstr1, 2A, 3, and 5 and analysed their presence, cellular localisation, distribution, and expression pattern in 33 gastrinomas, 36 insulinomas, and 35 tumours associated with a carcinoid syndrome by immunohistochemistry at the translational level. METHODS: Western blotting experiments were performed in the normal human pancreas used as a reference organ and in tumour tissues; at the cellular level, sstrs were localised by immunohistochemistry in tissue paraffin sections. RESULTS: In western blot analyses, the antibodies identified the respective receptors in their correct molecular range in extracts of the pancreas and neuroendocrine tumours. Using immunohistochemistry and immunofluorescence, the antibodies specifically detected the receptors in islet cells of the normal pancreas. Immunohistochemistry in the tumours revealed that all investigated sstr subtypes were highly expressed in the different tumour types. The frequency and expression pattern of the individual sstr subtypes varied considerably not only between the different tumour types but also in each patient. CONCLUSIONS: We conclude that immunohistochemistry with subtype specific antibodies can be used in clinical routine work to analyse sstr expression patterns for each patient before treatment and to facilitate well directed individual medical therapy by administering subtype specific somatostatin analogues. PMID- 11772968 TI - Interventional study of high dose folic acid in gastric carcinogenesis in beagles. AB - BACKGROUND: A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers. AIMS: To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles. METHODS: Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2 3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured. RESULTS: In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05). CONCLUSIONS: Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles. PMID- 11772969 TI - Endothelin-1 stimulates human colonic myofibroblast contraction and migration. AB - BACKGROUND: Although the contractile, migratory, and proliferative responses of subepithelial myofibroblasts to injury have been postulated to be important events in intestinal wound healing, contractile force generation and migration by these cells has not been investigated previously, and the signals that regulate proliferation by these cells are poorly understood. AIMS: The primary aim of this study was to test the hypothesis that the inflammatory mediator endothelin-1 modulates contraction, migration, and proliferation of intestinal myofibroblasts. We also sought to examine the signal transduction pathways which might underlie these putative effects. METHODS: Contraction, migration, proliferation, cytosolic [Ca(2+)], and myosin phosphorylation were measured in human colonic subepithelial myofibroblasts in the absence and presence of endothelin receptor agonists and antagonists. RESULTS: Endothelin-1, but not interleukin 1 alpha, interleukin 6, interleukin 8, interleukin 10, or tumour necrosis factor alpha, induced a rapid and robust generation of contractile force, which was associated with an increase in cytosolic [Ca(2+)] and myosin phosphorylation. Inhibition of rho associated kinase reduced endothelin-1 stimulated myosin phosphorylation and contractile force development. Endothelin-1 stimulated migration with a dose-response relationship similar to that observed for contraction. Endothelin A and B receptors mediated contraction while migration was mediated predominantly through endothelin B receptors. Platelet derived growth factor and serum, but not endothelin-1, induced proliferation. CONCLUSIONS: Endothelin-1 stimulates colonic subepithelial myofibroblast contraction and migration via endothelin receptor mediated myosin phosphorylation. These results support an important role for subepithelial myofibroblasts in the injury response of the gut and consequently intestinal wound repair. PMID- 11772970 TI - Activation of caspases in intestinal villus epithelial cells of normal and nematode infected rats. AB - BACKGROUND: Small intestinal epithelial cells (IEC) show apoptosis in physiological turnover of cells and in certain inflammatory diseases. AIMS: To investigate the role of caspases in the progression of IEC apoptosis in vivo. METHODS: IEC were separated along the villus-crypt axis from the jejunum of normal and Nippostrongylus brasiliensis infected rats at 4 degrees C. Caspases were examined by a fluorometric assay method, histochemistry, and immunoblotting. RESULTS: Villus cell rich IEC from normal rats exhibited a high level of caspase 3-like activity whereas activities of caspase-1, -8, and -9 were negligible. Immunoblotting analysis of villus cell rich IEC revealed partial cleavage of procaspase-3 into a 17 kDa molecule as well as cleavage of a caspase-3 substrate, poly(ADP-ribose) polymerase (PARP), whereas in crypt cell rich IEC, caspase-3 cleavage was less significant. Caspase-3 activity was also observed histochemically in villus epithelium on frozen sections of the normal small intestine. IEC prepared at 4 degrees C did not reveal nuclear degradation whereas subsequent incubation in a suspension at 37 degrees C induced intense nuclear degradation within one hour in accordance with increases in active caspase-3. This apoptosis was partially suppressed by the caspase inhibitor Z-VAD-fmk. Nematode infected animals showed villus atrophy together with significant increases in levels of caspase-3 in IEC but not of caspase-1, -8, or -9. CONCLUSION: Caspase-3 may have an important role in the physiological replacement of IEC as well as in progression of IEC apoptosis induced by nematode infection. PMID- 11772971 TI - Both thermal and non-thermal stress protect against caerulein induced pancreatitis and prevent trypsinogen activation in the pancreas. AB - BACKGROUND AND AIM: Recent studies have indicated that prior thermal stress causes upregulation of heat shock protein 70 (HSP70) expression in the pancreas and protects against secretagogue induced pancreatitis. The mechanisms responsible for the protective effect are not known. Similarly, the effects of prior non-thermal stress on HSP70 expression and pancreatitis are not known. The current studies were designed to specifically address these issues. METHODS: In the current studies pancreatitis was induced by administration of a supramaximally stimulating dose of caerulein 12 hours after thermal stress and 24 hours after non-thermal (that is, beta adrenergic stimulation) stress. RESULTS: Both thermal and non-thermal stresses caused pancreatic HSP70 levels to rise and resulted in increased expression of HSP70 in acinar cells. Both forms of stresses protected against caerulein induced pancreatitis and prevented the early intrapancreatic activation of trypsinogen which occurs in this model of pancreatitis. CONCLUSIONS: These results suggest that both thermal and non thermal stresses protect against pancreatitis by preventing intrapancreatic digestive enzyme activation and that HSP70 may mediate this protective effect. PMID- 11772972 TI - Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2. AB - BACKGROUND AND AIMS: Coeliac disease is characterised by atrophy of the villi and hyperplasia of the crypts in the mucosa of the small intestine. It is caused by an environmental trigger, cereal gluten, which induces infiltration of the mucosa by inflammatory cells. We hypothesised that these inflammatory cells express cyclooxygenase 2 (COX-2), an enzyme that contributes to the synthesis of pro and anti-inflammatory prostaglandins and is known to be expressed at sites of inflammation in the stomach and colon. We have investigated expression of COX-2 in the coeliac disease affected small intestinal mucosa where it may be an indicator of either disease induction or mucosal restoration processes. PATIENTS AND METHODS: Small intestinal biopsy samples from 15 coeliac patients and 15 non coeliac individuals were stained immunohistochemically for COX-2. Samples from 10 of the patients were also stained after these patients had been on a gluten free diet for 6-24 months. Various cell type marker antigens were used for immunohistochemical identification of the type of cell that expressed COX-2. To further verify colocalisation of the cell type marker and COX-2, double immunoperoxidase and immunofluorescence methods were employed. Immunoelectron microscopy was used to investigate the subcellular location of COX-2. RESULTS: In all samples taken from coeliac patients, clusters of cells with strong immunoreactivity for COX-2 were found in those areas of the lamina propria where the epithelium seemed to blister or was totally detached from the basement membrane. These clusters were reduced in number or totally absent in samples taken after a gluten free diet. No such clusters were seen in any control samples. The density of COX-2 positive cells lining the differentiated epithelium decreased significantly from 13.5 (5.1) cells/10(5) microm(2) (mean (SD)) in the untreated patient samples to 6.5 (2.0) cells/10(5) microm(2) after a gluten free diet (p<0.001), and was 3.3 (1.9) cells/10(5) microm(2) in control samples (p<0.001 compared with untreated or diet treated coeliac samples). Staining for COX-2 was localised to CD3+ T cells and CD68+ macrophages in the mucosal lesions but not all of these cells were positive for COX-2. Immunoelectron microscopy revealed that the ultrastructure of the COX-2 positive cells resembled that of lymphocytes, and the immunoreaction was localised to the rough endoplasmic reticulum and the nuclear envelope. CONCLUSIONS: Our results show that in coeliac disease, blistering of small intestinal epithelial cells is associated with accumulation of COX-2 positive T cells, and the number of these cells decreases after a gluten free diet. These observations suggest that COX-2 mediated prostanoid synthesis contributes to healing of the coeliac mucosa and may be involved in maintenance of intestinal integrity. PMID- 11772973 TI - Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study. AB - BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. PMID- 11772974 TI - Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. AB - BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence. PMID- 11772975 TI - Epidemiology and economic burden of viral hepatitis: an observational population based study. AB - OBJECTIVE: To describe the epidemiology and estimate the health resource use of patients with viral hepatitis in Tayside, Scotland, using record linkage techniques. DESIGN: A retrospective observational study. SETTING: Liver disease database, Tayside, Scotland. PATIENTS: All subjects resident in Tayside in the study period 1989-1999 and registered on the Epidemiology of Liver Disease in Tayside (ELDIT) database. MAIN OUTCOME MEASURES: Incidence and prevalence of known viral hepatitis in Tayside, survival of subjects diagnosed with viral hepatitis, and the health resource use with respect to hospital admissions compared with the general population. RESULTS: There were 4992 patients identified with viral hepatitis in the study period 1989-1999; 86 were IgM positive anti-hepatitis A, 187 patients were hepatitis B surface antigen (HBsAg) positive, and 469 were anti-hepatitis C (HCV) positive. HCV and HBsAg seropositive patients were more likely to be hospitalised and stay in hospital longer, less likely to survive after six years, and used more drugs of potential abuse than the general population. There was an increase in cost per admission and per patient as a consequence of liver disease. CONCLUSIONS: A record linkage population based study of viral hepatitis allows outcomes to be identified and costed. Those at risk of viral hepatitis infection in the Tayside population should be informed about the future implication to their health and costs to society. The health service should investigate the cost effectiveness of vaccination and opportunity costs to the health service of viral hepatitis taking into consideration the increasing incidence and prevalence of disease. PMID- 11772976 TI - Evaluation of serum cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver. AB - BACKGROUND AND AIMS: Diagnosis of moderately impaired renal function is of particular importance in patients with cirrhosis of the liver. Whereas patients with a markedly impaired glomerular filtration rate can be diagnosed easily by elevated serum creatinine concentrations, moderately reduced renal function may be missed by this conventional parameter. Recently, cystatin C has been suggested as a sensitive marker of renal function, independent of sex or muscle mass. Therefore, the aim of this study was to investigate the value of serum cystatin C concentration for the detection of moderately impaired renal function. METHODS: Ninety seven in-hospital patients with cirrhosis and a 24 hour creatinine clearance of at least 40 ml/min were investigated and divided into group 1 (creatinine clearance > or = 70 ml/min; n = 55) and group 2 (creatinine clearance 40-69 ml/min; n = 42). RESULTS: Serum cystatin C concentrations (mean (SD): 1.31 (0.51) v 1.04 (0.34) mg/l (p = 0.008)) and creatinine concentrations (1.03 (0.52) v 0.86 (0.22) mg/100 ml (p=0.03)) were higher in group 2 than in group 1; there was no significant difference in urea concentrations. Receiver-operator characteristics (ROC) revealed a differential diagnostic advantage of cystatin C over creatinine and urea. At cut off concentrations of 1.0 mg/l, 0.9 mg/100 ml, and 28 mg/100 ml, respectively, cystatin C, creatinine, and urea exhibited 69%, 45%, and 44% sensitivity (p<0.05). As patients with a small muscle mass or reduced physical activity could be particularly prone to overestimation of their renal function, separate analyses were performed for the subgroups of female and Child-Pugh class C patients, respectively. In both groups, discrimination between patients with moderately impaired and normal renal function was best with cystatin C. In female patients, sensitivity of cystatin C (77.8%) was superior (p<0.05) to that of creatinine (38.9%) and urea (41.2%). In Child-Pugh C patients, the ROC curve was significantly better for cystatin C than for creatinine. CONCLUSIONS: Serum cystatin C determination could be a valuable tool in patients with cirrhosis, particularly with Child-Pugh class C or in female patients, for early diagnosis of moderately impaired renal function. PMID- 11772977 TI - Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure. AB - BACKGROUND AND AIMS: Renal failure occurs in approximately 55% of patients with acute liver failure. We have previously shown that plasma endothelin 1 concentrations are elevated in patients with acute liver failure and the hepatorenal syndrome. There are few reported satisfactory animal models of liver failure together with functional renal failure. In this study, a rat model of acute liver failure induced by galactosamine that also develops renal failure was first characterised. This model was used to investigate the hypothesis that endothelin 1 is an important mediator involved in the pathogenesis of renal impairment that occurs in acute liver failure. METHODS: Acute liver failure was induced in male Sprague-Dawley rats by intraperitoneal injection of galactosamine together with treatment with the endothelin receptor antagonist Bosentan. Twenty four hour urine collections were made using a metabolic cage. Renal blood flow was measured in anaesthetised animals. RESULTS: This model developed renal failure and liver failure in the absence of any significant renal pathology, and with an accompanying fall in renal blood flow. Plasma concentrations of endothelin 1 were increased twofold following the onset of liver and renal failure (p<0.05), and there was significant upregulation of the endothelin receptor A (ET(A)) in the renal cortex (p<0.05). Administration of Bosentan prevented the development of renal failure when given before or 24 hours after the onset of liver injury (p<0.05) but had no effect on liver injury itself, or on renal blood flow. CONCLUSIONS: This study demonstrates that this animal model has many of the features needed to be regarded as a model of renal failure that occurs in acute liver failure. The observation that plasma levels of endothelin 1 and ET(A) receptors are increased and upregulated, and that renal failure is prevented by an endothelin antagonist supports the hypothesis originally put forward that ET(A) is important in the pathogenesis of renal failure that occurs in patients with acute liver failure. PMID- 11772978 TI - Biliary drainage for obstructive jaundice enhances hepatic energy status in humans: a 31-phosphorus magnetic resonance spectroscopy study. AB - BACKGROUND: Biliary obstruction impairs liver function although the pathophysiological mechanism is incompletely understood. AIMS: The aim of this study was to examine serial changes in liver metabolism in patients with obstructive jaundice using image guided in vivo 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). This technique allows repeated and non-invasive assay of organ energy metabolism and phospholipid biochemistry. PATIENTS: We studied 10 patients presenting with obstructive jaundice secondary to extrahepatic localised malignancy. There were eight men and two women, median age 72 years (range 54 94), six with cholangiocarcinoma (all Bismuth type 1) and four with carcinoma of the head of the pancreas. Ten healthy volunteers (median age 24 years (range 21 26)) were studied for comparison. METHODS: Hepatic metabolism in jaundiced patients was measured by (31)P MRS at presentation and again after a one week period of biliary drainage. Conventional liver function tests were also recorded. RESULTS: Compared with controls, liver spectra from jaundiced patients contained an excess of phosphomonoester (PME) metabolites (PME/total phosphate median 10.3% (interquartile range 8.7-11.5) in controls, 15.4% (13.1-17.7) in jaundiced cases; p<0.01). Biliary decompression was achieved in all patients (five with internal stents and five by external drainage catheters), and plasma biochemistry improved predictably (bilirubin 176 micromol/l (158-351) at presentation, 110 micromol/l (42-241) after drainage for one week; p<0.01). Enhancement of hepatic energy status, measured by the ratio of adenosine triphosphate (ATP) to inorganic phosphate (Pi), was observed in all cases after relief of biliary obstruction (ATP/Pi 1.4 (1.17-1.69) at presentation, 1.97 (1.4-2.48) after drainage; p<0.01) and was independent of the route of bile drainage. Hepatic phosphodiester (PDE) content was decreased after relief of obstruction (PDE/total phosphate 25.2% (20.5-27.4) at presentation, 19.8% (16.6-24.5) after drainage; p<0.01). This change was probably due to a reduction in the contribution from bile contents to this resonance as a strong PDE signal was also detectable in spectra obtained from separate bile specimens. CONCLUSIONS: Obstructive jaundice produces alterations in liver phosphoester biochemistry, most likely reflecting disturbances in phospholipid metabolism. Relief of biliary obstruction is associated with a measurable increase in hepatic energy status. Bile may contribute to the phosphodiester signal of the 31-phosphorus liver spectrum and changes in these resonances must therefore be interpreted with caution and in relation to the clinical situation. Monitoring of liver metabolism by (31)P MRS may allow clinicians to refine the selection and timing of therapeutic options in jaundiced patients. PMID- 11772980 TI - The ulcer and the clip: which came first? PMID- 11772979 TI - Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. AB - BACKGROUND: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. AIMS: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. METHOD: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment-resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. RESULTS: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8-6.1 months with an acceptable cost ($40,000/ year of life gained) for waiting lists > or = 1 year whereas it was not cost effective ($74,000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2 6.7 months with a marginal cost of approximately $20,000/year of life gained in all cases, remaining cost effective for all waiting times. CONCLUSIONS: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage. PMID- 11772982 TI - Diagnosis of Wilson's disease: an experience over three decades. PMID- 11772981 TI - Gene therapy for liver diseases: recent strategies for treatment of viral hepatitis and liver malignancies. AB - Gene therapy has emerged as a powerful and very plastic tool to regulate biological functions in diseased tissues with application in virtually all medical fields. An increasing number of experimental and clinical studies underline the importance of genes as curative agents in the future. However, intense research is needed to evaluate the potential of gene therapy to improve efficacy and minimise the toxicity of the procedure. PMID- 11772983 TI - Small intestinal bacterial overgrowth, intestinal permeability, and non-alcoholic steatohepatitis. PMID- 11772984 TI - Learning from experience: research on health sector reform in the developing world. PMID- 11772985 TI - Pharmaceutical cost-containment policy: experiences in Shanghai, China. AB - BACKGROUND: In the decade after 1983, the annual growth rate of drug expenditure was about four times as high as that of per capita gross domestic product (GDP) in Shanghai. In 1993 and 1994, a drug list policy and hospital revenue capping policy were introduced in Shanghai to contain drug expenditure. We studied the impact of these two policies, as a model for similar policies in other parts of China and elsewhere. METHODS: Quarterly drug expenditure data were collected from 1992 to 1996 and more detailed drug expenditure flow was obtained at seven selected hospitals. Twelve focus group discussions were organized to obtain opinions from all stakeholders. RESULTS: The research findings showed a dramatic and continuing decline in the growth rates of total medical and drug expenditures after the implementation of the two policies. The proportion of total medical expenditure attributable to drugs declined from 67% in 1992 to 51% in 1996. The annual growth rate of drug expenditure per ambulatory visit and per bed-day was reduced as well. Drug revenue as a proportion of total hospital revenue declined gradually in all seven hospitals. The two policies did not alter the equity of drug utilization between the insured and non-insured. The government, insurance authority and state-owned drug enterprises all favoured the new policies, while hospital administrators, professionals, joint venture and foreign manufacturers wished for the reimbursement mechanisms to be improved, for retention of their freedom of choice, and for the drug list to be further expanded. CONCLUSIONS: The drug list and capping policies in Shanghai appear to have achieved their objectives of containing the escalation of drug expenditure and improving the rational use of drugs without loss of equity. The underlying causes of the escalation of drug expenditure in China need to be further elucidated. PMID- 11772986 TI - Cost recovery beds in public hospitals in Indonesia. AB - A policy of allowing public hospitals to provide some better quality, higher priced hospital beds for those able to pay was introduced as government policy in Indonesia after 1993. A study was conducted in 1998 in three public hospitals in East Java to investigate if the policy objective of cost-recovery was being achieved. Hospital revenue from these commercial beds was less than both the recurrent and total costs of providing them in all three hospitals, but exceeded recurrent costs minus staff salaries in two hospitals. One reason for the low cost-recovery ratios was that between 55% and 66% of the revenue was used as staff incentives, mostly to doctors. This was more than the maximum of 40% stipulated in the policy. The high proportions of total revenue going to staff were a result of hospital management having set bed fees too low. The policy may be contributing to the retention of doctors within public sector employment; however, it is not achieving its stated objective, especially over the longer term where full recovery of salaries and investment costs needs to be considered. Public hospitals that wish to invest in commercial beds need effective management and accounting systems so as to be able to monitor and control costs and set fees at levels that recoup the costs incurred. Further research is required to determine if this form of public-private mix has negative effects on equity and access for poorer patients. PMID- 11772987 TI - User-payment, decentralization and health service utilization in Zambia. AB - The study was undertaken to assess the impact of health sector reform from 1993 to 1997 in Zambia in respect of health care service utilization and the shift of caseload from hospitals to health centres. Four key indicators were chosen: general attendance, measles vaccinations, general admissions, and deliveries. Complete sets of district data were analyzed, covering 4.5 million people out of the total population in 1997 of 9.7 million. The results show, on the one hand, a dramatic decrease of about one-third in general attendance for both hospitals and health centres over a 2-year period, followed by a period with a continued but slower decrease. On the other hand, the results also show increases at health centres in measles vaccinations (up 40%), in admissions (up 25%) and in deliveries (up 60%). The study further documents a shift of caseload from hospitals to health centres for some key services. The health centre share increased from 72.2% to 79.8% for measles vaccinations, from 23.9% to 31.0% for general admissions, and from 22.9% to 32.4% for deliveries. However, the intended overall shift in outpatient caseload from hospitals to health centres did not materialize. The main lessons are: utilization patterns can be influenced by policies such as user-payment and decentralization; user payment in poor populations leads to dramatic declines in utilization of services; and decentralization with local control of resources could be an alternative to the traditional vertical disease programme approach for priority interventions. PMID- 11772988 TI - The challenge of hospitals in health sector reform: the case of Zambia. AB - Zambia underwent a period of health sector reform from 1993 to 1998. The reform attracted substantial support from the World Bank and bilateral donors. While significant achievements were made with respect to decentralization, increased accountability and donor collaboration, the reform stalled in 1998 without having achieved its objectives, largely because of the handling of hospital reform and the civil servants in the health sector. This study was an attempt to analyze this experience with the hospital issue. Service and infrastructure information was collected from all 88 hospitals in the country. Further, information was collected about the social, economic, and political context of the reform. The results show that an historical legacy from the colonial and post-colonial eras has left the country with an expensive and skewed hospital structure that is rapidly deteriorating and very difficult to reform. The referral system is not functioning: higher-level hospitals provide a higher level of care to their immediate catchment populations than is available to the population in general. The reality is thus far from the vision of equity of access to cost-effective quality care. Zambian doctors have either left the country or are concentrated at the highest referral levels in two provinces, leaving the lower levels and most of the country in the hands of expatriate doctors. There are no resources in the government or the private systems to maintain the current hospital infrastructure and things will likely deteriorate unless radical decisions are taken and implemented. The study further shows that the question of hospital reform is a political high-risk zone. If the problems are to be dealt with, the Zambian planners must, together with the politicians, work to create a broad national consensus for understanding the situation, its urgency, and the limited options for forward action. PMID- 11772989 TI - Managed competition for the poor or poorly managed competition? Lessons from the Colombian health reform experience. AB - BACKGROUND: In 1993, Colombia enacted and subsequently implemented a radical reform in its system of providing health care for the poor, moving in a short time from a traditional model of providing health services in public hospitals to a managed competition model in which the government buys health insurance for the poor. This study examines and attempts to draw lessons from the early experience with this reform. METHODS: Information was gathered from document reviews and interviews with key actors at both the national and local levels. Other quantitative data, such as data from existing national surveys and financial operating data, were also used as available. RESULTS: The new system made important achievements in its first few years, including the enrollment of 7 million Colombians (about half of the targeted population) in health insurance plans and improving access to care. Nevertheless, there were substantial problems with the lack of managerial infrastructure and flow of information needed for the new system to function properly. Because of these difficulties, substantial resources were wasted, and insurance coverage did not always result in true access to health care. CONCLUSIONS: Other countries contemplating similar reforms should educate health administrators and the public, and establish solid administrative capacity in advance of implementation. In Colombia, many initial problems still need to be overcome while maintaining and extending the programme's important accomplishments. PMID- 11772990 TI - Strengthening user participation through health sector reform in Colombia: a study of institutional change and social representation. AB - The challenge of achieving community participation as a component of health sector reform is especially great in low- and middle-income countries where there is limited experience of community participation in social policy making. This paper concentrates on the social representations of different actors at different levels of the health care system in Colombia that may hinder or enable effective implementation of the participatory policy. The study took place in Cali, Colombia and focused on two institutional mechanisms created by the state to channel citizen participation into the health sector, i.e. user associations and customer service offices. This is a case study with multiple sources of evidence using a combination of quantitative and qualitative social science methods. The analysis of respondents' representations revealed a range of practical concerns and considerable degree of scepticism among public and private sector institutions, consumer groups and individual citizens about user participation. Although participation in Colombia has been introduced on political, managerial and ethical grounds, this study has found that health care users do not yet have a meaningful seat around the table of decision-making bodies. PMID- 11772991 TI - Community participation in local health boards in a decentralized setting: cases from the Philippines. AB - Decentralization has been associated traditionally with participation and empowerment in local decision-making. This study of four cases analyzed the role of local health boards in enhancing community participation and empowerment under a decentralized system in the Philippines. Local government units (LGUs) with functioning local health boards were compared with LGUs whose health boards were not meeting regularly as mandated by law. The study found that there were more consultations with the community, fund-raising activities, health initiatives and higher per capita health expenditure in LGUs with functioning local health boards. Only the mayors and municipal health officers felt empowered by devolution. In general, awareness of devolution and their potential roles in health decision-making was low among members of the community. These findings can be attributed to the socio-cultural and historical traditions of centralized governance with little popular participation, overall attitudes of the community and board members, perceptions of health as primarily a medical matter, economic circumstances of LGUs, and insufficient preparation for devolution. Recommendations are suggested in response to these findings. PMID- 11772992 TI - A stakeholder approach towards hospital accreditation in India. AB - Accreditation has been recommended as a mechanism for assuring the quality of private sector health services in low-income countries, especially where regulatory systems are weak. A survey was conducted in Mumbai, India, in 1997-98 to elicit the views of the principal stakeholders on the introduction of accreditation and what form it should take. There was a high level of support for the classical features: voluntary participation, a standards-based approach to assessing hospital performance, periodic external assessment by health professionals, and the introduction of quality assurance measures to assist hospitals in meeting these standards. Hospital owners, professional bodies and government officials all saw potential - though different - advantages in accreditation: for owners and professionals it could give them a competitive edge in a crowded market, while government officials reckoned it could increase their influence over an unregulated private market. Areas of disagreement emerged; for example, hospital owners were opposed to government or third party payment bodies having a dominant role in running an accreditation system. The growing strength of a health service user representative lobby in Mumbai is an additional reason why this would be a suitable place for piloting such a system. The biggest obstacle to introducing accreditation in poorly resourced settings, such as India, is in how to finance it. The provisional support of the principal stakeholders for such a development, demonstrated in this study, will require a commitment from government and policymakers if the potential benefits of accreditation to the health of the population are to be realised. PMID- 11772993 TI - The policy on public-private mix in the Ugandan health sector: catching up with reality. AB - An informal public-private mix in the health sector has always existed in Uganda, and policymakers, planners and the public in general have taken this for granted. There is now renewed effort to develop a comprehensive policy on the mix, but the policy process has proved to be tortuous and the mix has been interpreted differently by different stakeholders. While significant differences in opinion on the mix still remain, it is becoming clear that the new policy should enable health institutions, whether in the public or the private sector, to play roles in which they have clear comparative advantage over others. PMID- 11772994 TI - Disease-associated mutations in L1 CAM interfere with ligand interactions and cell-surface expression. AB - Mutations in the L1CAM gene cause a highly variable neurological disease described as X-linked hydrocephalus, MASA syndrome or spastic paraplegia type I. Over one-third of the mutations identified in affected boys are missense, unique to individual families and distributed primarily across the large extracellular domain of the L1 protein. We have examined the effects of 25 missense mutations on binding to homophilic (L1) and heterophilic (TAX-1) ligands as well as on intracellular trafficking. All but three of these result in reduced ligand binding or impaired movement to the surface of COS and CHO cells. Therefore, we demonstrate for the first time that most missense mutations found in affected families have functional consequences. Furthermore, mutations that are predicted to affect the structure of individual extracellular domains are more likely to affect intracellular processing and/or ligand binding than those mutations affecting surface properties of the molecule. PMID- 11772995 TI - Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions. AB - The completion of the human genome sequence will greatly accelerate development of a new branch of bioscience and provide fundamental knowledge to biomedical research. We used the sequence information to measure replication timing of the entire lengths of human chromosomes 11q and 21q. Megabase-sized zones that replicate early or late in S phase (thus early/late transition) were defined at the sequence level. Early zones were more GC-rich and gene-rich than were late zones, and early/late transitions occurred primarily at positions identical to or near GC% transitions. We also found the single nucleotide polymorphism (SNP) frequency was high in the late-replicating and replication-transition regions. In the early/late transition regions, concentrated occurrence of cancer-related genes that include CCND1 encoding cyclin D1 (BCL1), FGF4 (KFGF), TIAM1 and FLI1, was observed. The transition regions contained other disease-related genes including APP associated with familial Alzheimer's disease (AD1), SOD1 associated with familial amyotrophic lateral sclerosis (ALS1) and PTS associated with phenylketonuria. These findings are discussed with respect to the prediction that increased DNA damage occurs in replication-transition regions. We propose that genome-wide assessment of replication timing serves as an efficient strategy for identifying disease-related genes. PMID- 11772996 TI - The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes. AB - We investigated the genotypic variation in 50 red-green color vision deficient males (27 deuteranopes and 23 protanopes) of middle European ancestry who possess multiple genes in the X-linked photopigment gene array. We have previously shown that only the first two genes of the array are expressed and contribute to the color vision phenotype. Therefore, the hypothesis is that the first two genes possessed by multigene-dichromats encode pigments of identical or nearly identical spectral sensitivity: one gene normal (R or G) and the other a hybrid (G/R or R/G). The spectral sensitivities of the encoded pigments were inferred from published in vitro and in vivo data. The color vision phenotype was assessed by standard anomaloscopy. Most genotypes (92%) included hybrid genes whose sequence and position and whose encoded pigment correlated exactly with the phenotype. However, one and possibly two of the protanopes had gene arrays consistent with protanomaly rather than protanopia, since two spectrally different pigments may be encoded by their arrays. Two of the deuteranopes had only R- and G-photopigment genes, without any detectable G/R-hybrid genes or any as-of-yet identified point mutation or coding/promoter sequence deletions. Further, an unexpectedly high number of multigene-deuteranopes (11%) had the C203R mutation in their most upstream G-pigment gene, suggesting a founder effect of middle European origin for this mutation. About half of the protanopes possessed an upstream R/G-hybrid gene with different exon 2 coding sequences than their downstream G-pigment gene(s), which is inconsistent with published data implying that a single amino acid substitution in exon 2 can confer red-green color discrimination capacity on multigene-protans by altering the optical density of the cones. PMID- 11772997 TI - Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma. AB - Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of MAF, a basic region leucine zipper (bZIP) transcription factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in MAF in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of MAF. Our findings further implicate MAF/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile site. PMID- 11772998 TI - Acute regression of advanced and retardation of early aortic atheroma in immunocompetent apolipoprotein-E (apoE) deficient mice by administration of a second generation [E1(-), E3(-), polymerase(-)] adenovirus vector expressing human apoE. AB - Apolipoprotein E (apoE) is a 34 kDa glycoprotein with multiple actions that help protect against the development of atherosclerosis. Here, we have assessed the atheroprotective potential of an [E1(-), E3(-), polymerase(-)] adenovirus vector expressing human apoE, comparing intramuscular and intravenous (liver-directed) injections in hypercholesterolaemic apoE-deficient mice (apoE(-/-)). Intramuscular injections resulted in low expression of apoE and afforded no protection against atherogenesis. In contrast, 3 and 7 days after intravenous injections into young (6-8-week-old) apoE(-/-) mice, plasma levels of apoE were elevated and were accompanied by reductions in plasma cholesterol and normalization of lipoprotein profiles. Thereafter, plasma apoE was still detectable up to day 70, but gradually declined, although no humoral immune response was evoked, and there was a return to dyslipoproteinaemia. High levels of the vector genome were still present in livers of treated animals at 70 days, implying that decrease in apoE expression was due to cellular shutdown of the cytomegalovirus promoter. Importantly, liver-directed apoE gene transfer to these young mice retarded progression of atherosclerosis by 38% (treated, 8.21 +/- 1.05%; untreated, 13.26 +/- 0.98%, P < 0.05), during the 70 day study period. Moreover, when 10-month-old apoE(-/-) mice with advanced atherosclerosis were treated with the adenovirus vector, there was clear regression of aortic lesion area by 1 month [24.3 +/- 1.7% compared to 40.7 +/- 2.6% in baseline controls (P < 0.002)]. We conclude that the stability of the adenovirus vector genome in the livers of intravenously treated animals provides an ideal platform to evaluate liver-specific promoters for sustained transgene expression and control of atherosclerotic lesion pathology. PMID- 11772999 TI - Distinct subcellular expression of endogenous polycystin-2 in the plasma membrane and Golgi apparatus of MDCK cells. AB - Polycystin-2 is a predicted integral membrane protein with non-selective cation channel activity. The protein is encoded by the PKD2 gene, which is mutated in approximately 15% of patients with autosomal dominant polycystic kidney disease (ADPKD). Polycystin-2 can interact with the transmembrane protein polycystin-1, the product of the PKD1 gene. However, endoplasmic reticulum (ER) localization was reported for (heterologously expressed) polycystin-2 in cultured cells and baso-lateral localization has been reported in renal tissues. Using two polyclonal antisera raised against polycystin-2 we demonstrated distinct expression of the endogenous protein in the Golgi apparatus and the plasma membrane of MDCK cells. In contrast, most of the heterologously expressed polycystin-2 (PC2-EGFP) remained in the ER, substantially overlapping with the staining pattern of protein-disulfide isomerase (PDI), a marker for the ER. Only in a small subset of these cells weak plasma membrane signals were observed. Membrane staining was also suggested by immunoelectron microscopy and was confirmed by subcellular fractionation on sucrose density gradients. The plasma membrane staining disappeared following extraction with a buffer containing Triton X-100, whereas signals for polycystin-1 and E-cadherin remained visible, suggesting that polycystin-2 is neither tightly bound to the Triton X-100 insoluble cytoskeleton, nor to these proteins. We conclude that endogenous polycystin-2 is transported via the Golgi apparatus to the plasma membrane and has a broader membrane localization than polycystin-1. These data suggest that polycystin-2 can move freely in certain regions of the membrane where it probably functions as a channel, activated by, or in complex with, polycystin-1. PMID- 11773000 TI - Transduction of wild-type merlin into human schwannoma cells decreases schwannoma cell growth and induces apoptosis. AB - Mutations in both alleles of the tumour suppressor gene coding for merlin/schwannomin, an ERM family protein, cause the hereditary disease neurofibromatosis type 2 (NF2). NF2 is characterized by the development of multiple nervous system tumours especially vestibular schwannomas. Efficient oncoretrovirus-mediated gene transfer of different merlin constructs was used to stably re-express wild-type merlin in primary cells derived from human schwannomas. Using two-parameter FACS analysis we show that expression of wild type merlin in NF2 cells led to significant reduction of proliferation and G0/G1 arrest in transduced schwannoma cells. In addition, we show increased apoptosis of schwannoma cells transduced with wild-type merlin. Our findings in primary schwannoma cells from NF2 patients strongly support the hypothesis of merlin acting as a tumour suppressor and may help in understanding development of human schwannomas in NF2. PMID- 11773001 TI - Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19. AB - Dlk1 and Gtl2 are reciprocally imprinted genes located 80 kb apart on mouse chromosome 12. Similarities between this domain and that of the well characterized Igf2-H19 locus have been previously noted. Comparative genomic and epigenetic analysis of these two domains might help identify allele-specific epigenetic regulatory elements and common features involved in aspects of imprinting control. Here we describe a detailed methylation analysis of the Dlk1 Gtl2 domain on both parental alleles in the mouse. Like the Igf2-H19 domain, areas of differential methylation are hypermethylated on the paternal allele and hypomethylated on the maternal allele. Three differentially methylated regions (DMRs), each with different epigenetic characteristics, have been identified. One DMR is intergenic, contains tandem repeats and is the only region that inherits a paternal methylation mark from the germline. An intronic DMR contains a conserved putative CTCF-binding domain. All three DMRs have both unique and common features compared to those identified in the Igf2-H19 domain. PMID- 11773002 TI - Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. AB - Retinitis pigmentosa (RP), the commonest form of inherited retinal dystrophies is a clinically and genetically heterogeneous disorder. It is characterized by progressive degeneration of the peripheral retina leading to night blindness and loss of peripheral visual field. RP is inherited either in an autosomal dominant, autosomal recessive or X-linked mode. A locus (RP18) for autosomal dominant RP was previously mapped by linkage analysis in two large pedigrees to chromosome 1p13-q21. The human HPRP3 gene, the orthologue of the yeast pre-mRNA splicing factor (PRP3), localizes within the RP18 disease interval. The recent identification of mutations in human splicing factors, PRPF31 and PRPC8, led us to screen HPRP3 as a candidate in three chromosome 1q-linked families. So far, two different missense mutations in two English, a Danish family and in three RP individuals have been identified. Both mutations are clustered within a two-codon stretch in the 11th exon of the HPRP3 gene. Interestingly, one of the mutations (T494M) is seen repeatedly in apparently unlinked families raising the possibility of a mutation hot spot. This has been confirmed by haplotype analysis using SNPs spanning the HPRP3 gene region supporting multiple origins of the mutation. The altered HPRP3 amino acids, which are highly conserved in all known HPRP3 orthologues, indicate a major function of that domain in the splicing process. The identification of mutations in a third pre-mRNA splicing factor gene further highlights a novel mechanism of photoreceptor degeneration due to defects in the splicing process. PMID- 11773003 TI - Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? AB - Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry-rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA. PMID- 11773004 TI - Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. AB - We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R) lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway. PMID- 11773005 TI - Insulin-like growth factor-1 receptor in uveal melanoma: a predictor for metastatic disease and a potential therapeutic target. AB - PURPOSE: To investigate the expression of the insulin-like growth factor-1 receptor (IGF-1R) with special focus on its role in cell growth in uveal melanoma. METHODS: Paraffin material from 36 clinicopathologically well characterized cases of primary uveal melanomas (18 of which had metastasized to the liver) with more than 15 years' follow-up was used for immunohistochemical analysis. In the experimental studies, three uveal melanoma cell lines (OCM-1, OCM-3, and 92-1) were used. The expression level of IGF-1R in the cell lines was modulated by glycosylation inhibitors, and the IGF-1R was neutralized with the antibody alphaIR-3. Expression of IGF-1R was assayed by Western blot analysis and immunohistochemistry. Cell growth and survival were analyzed by cell counting, thymidine incorporation, and viability assays. RESULTS: Western blot analysis and immunohistochemistry confirmed that IGF-1R is expressed in uveal melanoma. Although 10 of 18 patients who died of metastasizing disease showed high IGF-1R expression, only 5 of 18 tumors from patients who survived for 15 years or more after enucleation exhibited a high IGF-1R expression. Kaplan-Meier analysis showed a significant association (P = 0.035) between a high IGF-1R expression and death due to metastatic uveal melanoma. Using in vitro experimental models, we found that inhibition of the IGF-1R activity (tyrosine phosphorylation) was associated with a drastic decrease in uveal melanoma cell viability. CONCLUSIONS: These data suggest an important role of IGF-1R in uveal melanoma. The significant association between high IGF-1R expression and death due to metastatic disease may be explained by the fact that IGF-1 is mainly produced in the liver, which is the preferential site for uveal melanoma metastases. These data also point to the possibility of therapeutically interfering with IGF-1R, which appears to be expressed preferentially in uveal melanomas that appear to follow an aggressive clinical course. PMID- 11773006 TI - Chromosomal imbalances in lymphoid tumors of the orbit. AB - PURPOSE: To identify chromosomal gains and losses in lymphoid tumors of the orbit and to examine whether such abnormalities are related to orbital presentation, disease severity, or risk for recurrent disease. METHODS: Biopsy specimens from 26 patients were examined by histomorphologic and immunohistochemical analysis. Lymphomas were classified according to the Revised European-American Lymphoma Classification. Chromosomal imbalances were detected by high-resolution comparative genomic hybridization (CGH). Clinical data were obtained by retrospective evaluation of medical records. RESULTS: Chromosomal imbalances were detected in 0 of 6 patients with idiopathic orbital inflammation, 0 of 2 with benign reactive lymphoid hyperplasia, 3 of 3 with highly malignant diffuse large B-cell lymphoma, 4 of 10 with marginal zone B-cell lymphoma, 0 of 1 with chronic lymphatic leukemia lymphoma, and 1 of 4 with immunocytoma. Among the low-grade malignancies, chromosomal imbalances were seen in 1 of 9 at stage IAE, 2 of 3 at stage IIE, and 2 of 3 at stage IVE. Chromosomal imbalances were observed in all primary tumors from the five patients that later developed recurrent disease. In 14 of 23 imbalances with intrachromosomal breaks outside the centromere region, the breaks were present at bands with known fragile sites. No chromosomal imbalances specific for orbital presentation were detected. CONCLUSIONS: Chromosomal imbalances were seen mainly in orbital lymphomas that were either highly malignant or at an advanced stage. CGH analysis of orbital lymphomas could be prognostically relevant, but further studies are required to confirm this notion. PMID- 11773007 TI - Localization and characterization of calcineurin in bovine eye. AB - PURPOSE: There are several aspects of the visual system that may be regulated by Ca2+- and calmodulin (CaM)-stimulated protein phosphatase. In the present study, the distribution and characterization of calcineurin (CaN) in bovine eye was determined. METHODS: Whole bovine eyes were either homogenized for purification or regionally dissected to determine CaN localization and activity. Dissected tissues were homogenized and Western blot analysis performed, using polyclonal anti-CaN antibodies, and assayed using p-nitrophenyl phosphate (PNPP) as a substrate to determine the dephosphorylation activity of CaN. Fresh samples were then prepared for immunohistochemistry and probed with polyclonal anti-CaN antibodies. RESULTS: CaN was found to be present in all eye tissues, although activity and protein expression varied. The highest levels of CaN activity and protein expression were found in the optic nerve, retina, and cornea. Immunohistochemical methods displayed similar results with additional staining of the optic nerve vasculature. Assays of purified CaN demonstrated that bovine eye CaN had regulatory properties similar to CaN isolated from other tissues. Probing eye tissues with CaN A isoform-specific antibodies demonstrated that eye tissues displayed variable distributions of the CaN Aalpha and CaN Abeta isoforms. CONCLUSIONS: The presence of CaN in the bovine eye provides a physiological pathway by which the phosphorylated state of proteins and intracellular Ca2+ concentrations can be coordinated. The authors propose that CaN is involved in the immunologic privilege of the cornea, retinal signal transduction, and the toxic effects of immunosuppressants on the eye. Further in vivo studies of CaN function are necessary to understand the contributions of CaN to ocular physiology. PMID- 11773008 TI - Identification and subcellular localization of the RP1 protein in human and mouse photoreceptors. AB - PURPOSE: Mutations in the RP1 gene account for 6% to 10% of autosomal dominant retinitis pigmentosa (adRP). Previous studies have shown that the RP1 gene is expressed specifically in photoreceptor cells. So far, little is known about the RP1 protein or how mutations in RP1 lead to photoreceptor cell death. The goal of this study was to identify the RP1 protein and investigate its location in photoreceptor cells. METHODS: A combination of RT-PCR and rapid amplification of cDNA ends (RACE) was used to isolate the full-length mouse Rp1 cDNA. Antibodies against different regions of the predicted mouse Rp1 protein were generated. Western blot analyses were used to identify the RP1/Rp1 proteins. The subcellular location of RP1 in human and mouse retinas was determined by immunostaining retinal sections. RESULTS: The full-length mouse Rp1 cDNA is 6944 bp, encoding a predicted protein of 2095 amino acids. Rp1 was found to be a soluble protein of approximately 240 kDa, consistent with predictions based on the cDNA sequence. Immunofluorescence analyses revealed that both the human RP1 and mouse Rp1 proteins are specifically localized in the connecting cilia of rod and cone photoreceptors. CONCLUSIONS: The presence of RP1/Rp1 in connecting cilia suggests that it may participate in transport of proteins between the inner and outer segments of photoreceptors or in maintenance of cilial structure. This study forms the basis for further investigation of the function of RP1 in retina and the mechanism by which mutations in RP1 lead to photoreceptor cell death. PMID- 11773009 TI - Effects of elevated intraocular pressure on outflow facility and TIGR/MYOC expression in perfused human anterior segments. AB - PURPOSE: To investigate the effects of high intraocular pressure (h-IOP) on TIGR/MYOC expression, extracellular matrix (ECM) deposition, and outflow facility (C) in perfused human anterior segment cultures. METHODS: Anterior segments of 31 pairs of normal human eyes from postmortem donors were perfused at constant flow (3 microl/min). After reaching stable baseline, the flow of one eye from each of 31 pairs was raised to obtain a continuous pressure of 60 to 70 mm Hg for a period of 1 hour (3 pairs), 6 hours (10 pairs), 24 hours (2 pairs), 48 hours (3 pairs), and 7 days (13 pairs). Sixteen of these pairs were used to study trabecular meshwork expression of TIGR/MYOC and stromelysin by Northern blot analysis hybridization. Nine pairs (1 pair each at h-IOP for 1, 6, and 48 hours and 6 pairs at 7 days) were fixed at pressure for analysis by electron microscopy. Eyes selected for C measurements fulfilled the inclusion criteria of C0 values between 0.06 and 0.4, intact RNA recovery and normal light microscopy morphology. Percent change of facility from the baseline (C/C0) was computed at 6 and 24 hours and 2, 4, and 7 days from the long-term perfusion experiments (n = 9 h-IOP, n = 8 controls). RESULTS: No induction of TIGR/MYOC expression was observed after h-IOP for 1 and 6 h. A slight induction was seen after 24 and 48 hours. At 7 days, the treated eye from 4 of 5 pairs showed a clear induction, which was very pronounced in one of the pairs. In contrast, stromelysin expression was induced at 6 hours and not at 7 days. Morphometric electron microscopy after 7 days showed no significant difference in the amounts of fine fibrillar material or plaque material in the juxtacanalicular (JCT) region. The percent increase of C of the treated eye at 6 hours was 11.0% +/- 4.6% compared with 3.7% +/- 3.8% in the control eyes (P = 0.26). However, after longer time periods, the facility of the h-IOP eyes increased, whereas that of the contralateral eyes remained unchanged. This difference reached peak, significant values at 4 days (32.9% +/- 8.4% versus 7.4% +/- 7.6%, respectively; P = 0.04) and decreased to 8.9% +/- 7.9% versus 1.1% +/- 12.7% (P = 0.6) at 7 days. CONCLUSIONS: Elevated IOP appears to cause a decrease in outflow pathway resistance at 1 to 4 days, and this effect seems to disappear with further time. In contrast, induction of TIGR/MYOC appears to be strongest at 7 days. We speculate that this induction pattern might indicate a stress-related, rather than a possible homeostatic, role for the TIGR/MYOC protein. PMID- 11773010 TI - TGFbeta1-dependent contraction of fibroblasts is mediated by the PDGFalpha receptor. AB - PURPOSE: Contraction of fibroblasts and the resultant tractional force is a contributing factor to fibrotic diseases of the eye, such as proliferative vitreoretinopathy (PVR). Transforming growth factor (TGF)-beta is abundant in the eye, and is one of the growth factors thought to contribute to the development of PVR. A second is platelet-derived growth factor (PDGF). In the current study, the relationship between TGFbeta1 and PDGF was investigated at the level of cellular contraction. METHODS: To study cellular contraction, an in vitro type I collagen gel contraction assay was used with a panel of fibroblast lines that expressed the PDGFalpha receptor (alphaPDGFR) or PDGFbeta receptor (betaPDGFR) or no PDGFRs. The agents tested included rabbit vitreous, TGFbeta1, and PDGF. RESULTS: Vitreous promoted cellular contraction, and approximately 60% of this activity was eliminated by preincubation of the vitreous with neutralizing TGFbeta antibodies. The alphaPDGFR-expressing cells responded better than cells expressing the betaPDGFR or no PDGFRs. Both of the PDGFR-expressing cell lines contracted in response to PDGF, whereas the best response to TGFbeta1 was observed with cells expressing the alphaPDGFR. Finally, TGFbeta1 promoted the tyrosine phosphorylation of both of the PDGFRs, and the alphaPDGFR was more strongly phosphorylated than the betaPDGFR. CONCLUSIONS: The results show that the vitreous promotes cellular contraction, that TGFbeta is the major factor responsible, and that at least a portion of the TGFbeta-dependent contraction proceeds through the alphaPDGFR-that is, indirectly. Therefore, the alphaPDGFR is responsible for mediating cellular contraction of multiple growth factors: TGFbeta and members of the PDGF family. PMID- 11773011 TI - Macular pigment density is reduced in obese subjects. AB - PURPOSE: Because of the potential protective function of lutein (L) and zeaxanthin (Z) within the retina and lens, a better understanding of factors influencing tissue deposition is needed. The largest fractions of L and Z are stored in adipose tissue. Thus, higher body fat content and body mass index (BMI) may be expected to influence the quantities of L and Z in the retina (measured as macular pigment optical density, MPOD). METHODS: Six hundred eighty subjects were tested. Information on MPOD, body mass index (BMI), body fat percentage (n = 400, using bioelectric impedance), dietary intake (n = 280, using a food frequency questionnaire), and serum carotenoid content (n = 280, using reversed phase high performance liquid chromatography) was obtained. RESULTS: There was an inverse relationship between MPOD and BMI (n = 680, r = -0.12, P < 0.0008) and between MPOD and body fat percentage (n = 400, r = -0.12, P < 0.01). These relationships were largely driven by data from the subjects with higher BMI (more than 29, 21% less MP) and higher body fat percentage (more than 27%, 16% less MP). Dietary carotenoid intake and serum carotenoid levels were also lower in subjects with higher BMI (n = 280). CONCLUSIONS: Obese subjects tend to have lower retinal L and Z. This reduction may be due to decreased dietary intake of L and Z and/or competition between retina and adipose tissue for uptake of L and Z. PMID- 11773013 TI - CC-chemokine receptor 3: a possible target in treatment of allergy-related corneal ulcer. AB - PURPOSE: To determine the suppressive effects of antibodies (Abs) against CC chemokine receptor (CCR)-1 and CCR-3 on eosinophil chemotaxis induced by culture supernatant from corneal keratocytes and by tears from severely allergic patients with corneal ulcer. METHODS: Primary cultures of human corneal keratocytes were incubated with interleukin (IL)-4 (33.3 ng/mL) and tumor necrosis factor (TNF) alpha (33.3 ng/mL) for 48 hours. In tear samples collected from five severely allergic patients and three nonallergic control subjects, eosinophils were immunostained for CCR. Next, eosinophils purified from peripheral blood were preincubated with or without anti-CCR-1 and anti-CCR-3 Abs before a Boyden chamber assay was conducted. Recombinant human (rh) eotaxin, rh-regulated on activation normal T-cell expressed and secreted (rh-RANTES), culture supernatant from human corneal keratocytes, and tear samples were used as chemoattractants. RESULTS: Eosinophils in tears from allergic patients expressed CCR-1 and -3 on their surfaces. Anti-CCR-1 and -3 Abs each inhibited eosinophil chemotaxis induced by rh-RANTES. Anti-CCR-3 Ab (but not anti-CCR-1 Ab) also inhibited eosinophil chemotaxis induced by rh-eotaxin. Anti-CCR-1 and -3 Abs, respectively, inhibited up to 75.2% and 94.6% of eosinophil chemotaxis induced by culture supernatant, as well as 27.8% and 74.5% of chemotaxis induced by tear samples. CONCLUSIONS: Anti-CCR-1 and -3 Abs inhibited eosinophil chemotaxis induced by culture supernatant from corneal keratocytes and tear samples from severely allergic patients. Anti-CCR-3 Ab was more effective than anti-CCR-1 Ab. Inhibition of CCR-3 on eosinophils may be a treatment for corneal ulcer in patients with ocular allergy. PMID- 11773012 TI - Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region. AB - PURPOSE: To better understand the pathogenesis of hereditary keratoconus, an inbred line of spontaneous mutant mice with keratoconus-affected corneas (SKC mice) was established and studied with a multidisciplinary approach. METHODS: Using a mutant mouse with corneas having a keratoconical appearance as the progenitor, an inbred line of SKC mouse was established by repeated sibling mating. Morphology, cell growth, apoptosis and protein expression of SKC mouse corneas were examined. Castration of males and androgen treatment for females were conducted to determine any androgen dependency of the phenotype. Linkage analysis was conducted to reveal the responsible or predisposing gene of SKC mouse keratoconus. RESULTS: Corneas of the SKC mouse resemble those of human eyes with keratoconus. Both are conical and show similar corneal changes, including apoptosis of keratocytes and increased expression of c-fos protein. The SKC mouse phenotype was transmitted in an autosomal recessive manner, although it was observed almost exclusively in males. Intriguingly, female mice showed the phenotype when injected with testosterone, whereas male incidence of the phenotype diminished drastically when mice were castrated. Linkage analysis localized a predisposition locus to an MHC region on mouse chromosome 17, which includes a locus for the gene for sex-limited protein (Slp). CONCLUSIONS: SKC mouse keratoconus is a potential model for a subset of human keratoconus, which is a disease entity with heterogeneous pathogeneses. Alternatively, SKC mouse keratoconus could be a model for other human or mouse-specific keratopathies. PMID- 11773014 TI - Connexin 43 expression and proliferation of human limbal epithelium on intact and denuded amniotic membrane. AB - PURPOSE: Stem cell (SC)-containing limbal basal epithelium and transient amplifying cell (TAC)-containing corneal basal epithelium lie on different mesenchymal matrices. The gap junction protein connexin 43 (Cx43) is absent in the limbal basal epithelium but is present in the corneal basal epithelium, suggesting that the expression of Cx43 denotes SC differentiation into TACs. Amniotic membrane (AM) can expand limbal epithelial progenitor cells in vivo and in culture for subsequent corneal surface reconstruction. In this study, the modulation of Cx43 expression, gap junction intercellular communication (GJIC), and proliferative activity of ex vivo expanded human limbal epithelial (HLE) cells on intact and epithelially denuded AM was investigated. METHODS: HLE cells were expanded on intact (i.e., remaining devitalized amniotic epithelium) or epithelially denuded AM (EDTA-treated). Cx43 expression and 24-hour 5-bromo-2' deoxyuridine-5'monophosphate (BrdU) labeling index (percentage) were determined by double immunostaining. GJIC was investigated by a scrape-loading dye transfer assay. In a subset of cultures Cx43 and K3 keratin as well as BrdU-retaining nuclei were analyzed in the stratified epithelium obtained 5 days after subcutaneous transplantation in NIH bg-nu-xidBR mice of AM cultures continuously labeled with BrdU for 7 days. RESULTS: The outgrowth rate, overall, was significantly higher on EDTA-treated AM than on intact AM (P < 0.05). Cx43 was expressed in 12.4% +/- 14.5% (n = 5) on intact and 57.5% +/- 18.2% (n = 5) on EDTA-treated AM (P < 0.05). The BrdU labeling index was 2.4% +/- 0.9% (n = 5) for the intact AM group, which was significantly less than 22.5% +/- 8.2% (n = 5) for EDTA-treated AM (P < 0.05). BrdU-labeled cells did not express Cx43. The dye transfer assay revealed reduced GJIC on both AM-cultured groups compared with the control culture on plastic (P < 0.002). GJIC on intact AM (17%) was reduced compared with that on EDTA-treated AM (27%; P = 0.42). After xenotransplantation, the basal layer of the stratified epithelium was Cx43 and K3 keratin negative and retained BrdU on intact AM, resembling characteristics of the limbal basal epithelium in vivo. In contrast, that of EDTA-treated AM was Cx43 and K3 keratin positive without BrdU retention, resembling characteristics of the corneal epithelium in vivo. CONCLUSION: These data indicate that denudation of the devitalized amniotic epithelium to expose its basement membrane might be a microenvironmental cue to promote TAC differentiation. The model system described herein is ideal for future exploration of the exact mechanistic operation in the microenvironmental niche that maintains the "stemness" of limbal SCs as well as in the signal that promotes corneal TAC differentiation. PMID- 11773015 TI - Differential effect of activin A and BMP-7 on myofibroblast differentiation and the role of the Smad signaling pathway. AB - PURPOSE: To investigate myofibroblast differentiation and signal transduction induced by TGF-beta family members activin A and bone morphogenetic protein (BMP) 7. METHODS: Transcription of activin and receptors (ActR) for activin A and BMP-7 was detected by RT-PCR. Levels of marker proteins for differentiation and phosphorylation of similar to mothers against decapentaplegics (Smads) were quantified by Western blot analysis in response to BMP-7, activin A and follistatin. Transfection with antisense Smad2/3 was performed to evaluate signal transduction. RESULTS: Activin A and receptors (ActR-I, ActR-IB, ActR-II) are transcribed in corneal fibroblasts. Compared with TGF-beta1 or serum, activin A but not BMP-7 increased alpha-smooth muscle (SM) actin and actin-binding proteins such as SM myosin, alpha-actinin, and vinculin. Talin, paxillin, and desmin were not induced and vimentin was downregulated by activin. Activin also induced extracellular matrix proteins fibronectin and integrin beta1. Activin-dependent accumulation of proteins was blocked by follistatin. Regarding signal transduction, activin A induced phosphorylation of Smad 2, and BMP-7 induced Smad 1, both of which were inhibited by follistatin. Transfection with antisense Smad 2/3 prevented activin-induced expression and accumulation of alpha-SM actin. CONCLUSIONS: TGF-beta proteins have different functions in the cornea. Activin A and TGF-beta1, but not BMP-7, are regulators of corneal keratocyte differentiation and may play a role during myofibroblast transdifferentiation. Smad 2/3 signal transduction seems to be important in the regulation of muscle specific genes. Further investigation of Smad signaling may help to better understand the function of TGF-beta family members in the cornea. PMID- 11773016 TI - Linear birefringence of the central human cornea. AB - PURPOSE: To determine the polarization properties of the central cornea at perpendicular incidence in a normal human population on the assumption that the cornea behaves as a linear retarder. METHODS: A corneal polarimeter provided a view of the fourth Purkinje image of a yellow (585 nm) light-emitting diode through crossed polarizers and a variable retarder. The Purkinje image was extinguished by adjusting the fast axis and retardance of the retarder to match the slow axis and double-pass retardance of the cornea. Both eyes of 73 normal subjects (49 women, 24 men; ages, 21-71 years) were measured. Correlations were expressed as Pearson's r. RESULTS: In most corneas the slow axis pointed nasally downward, with the peak of the axis distribution falling between 10 degrees and 20 degrees nasally downward. Double-pass corneal retardance varied widely (range, 0-250 nm); 80% of retardance values were uniformly distributed from 40 to 140 nm. Retardance was moderately correlated with axis (r approximately 0.5), such that weaker retardance was associated with axes that were more nasally downward. Corneal birefringence was well correlated between the two eyes of a subject in both axis (r = 0.77) and retardance (r = 0.75). CONCLUSIONS: The variation of corneal birefringence among individuals is substantial enough to produce large, uncontrolled differences in the polarization state of a measuring beam, differences that can introduce variability in newer technologies for ophthalmic diagnosis. The interocular similarity of corneal birefringence suggests deterministic control of corneal development. PMID- 11773017 TI - Reflex and steady state tears in patients with latent stromal herpetic keratitis. AB - PURPOSE: To compare tear production in patients with stromal herpetic keratitis with that in healthy control subjects. METHODS: After instillation of 2 microL fluorescein into both eyes, the tear-fluorescein concentration was measured by fluorophotometry. During the first 10 minutes, steady state tear turnover (TTO-1) was determined. After a nasal alcohol stimulus to induce reflex tears, a second steady state tear turnover (TTO-2) was obtained during 15 minutes. The index of reflex lacrimation (IRL) was calculated as the percentage decrease in tear fluorescein concentration directly after the stimulus. TTO-1, TTO-2, and IRL were determined in the patients' affected eyes (n = 12), in the patients' healthy contralateral eyes, if possible (n = 9), and in one eye of healthy control subjects (n = 24). RESULTS: The TTO-1 in the affected and healthy eyes of patients was approximately two times lower than the TTO-1 in eyes of healthy control subjects (P = 0.012 and P = 0.024, respectively) and almost equal to the TTO-2 in eyes of healthy control subjects (P = 0.32 and P = 0.40). There were no significant differences in the values of TTO-1, IRL, and TTO-2 between affected and healthy eyes of patients (P > 0.5). IRL and TTO-2 did not differ significantly among the three groups (P > 0.5). CONCLUSIONS: Both eyes of the patients were dry. The dryness could be due to a defective reflex lacrimation under physiological conditions that can still be induced by nonphysiological nasal excitation. The cause of this may be demyelination of both trigeminal root entry zones as a result of a unilateral eye infection by the herpes virus. Another possibility is that dryness predisposes to herpetic infection or recurrent inflammation. PMID- 11773018 TI - A physiological model to measure effects of age on lenticular accommodation and spherical aberration in chickens. AB - PURPOSE: To assess physiological accommodative function of intact intraocular lenses, as measured by focal length changes, in chickens of various ages. METHODS: Eyes of white leghorn chickens, aged 0 days (hatchlings), 7 days, 14 days, 6 weeks, 1 year, and 2 years, were enucleated and the backs of the globes, except for the ciliary nerve and ganglion, were removed. The ciliary nerve and ganglion were suctioned into the tip of a suction electrode, and lenses were optically scanned before, during, and after accommodation. Accommodation was elicited by delivery of 30-Hz electrical pulses. RESULTS: For all age groups, lenticular focal lengths for stimulated eyes were significantly shorter than for relaxed eyes, indicating that accommodation had been induced. Lenticular accommodative amplitudes decreased significantly with age, with reduced function occurring between 0 and 7 days and again between 14 days and 1 year. Although accommodation was associated with an increased spherical aberration in all age groups, the increase was significant only in some age groups. CONCLUSIONS: Results showing reduction of lenticular accommodation concomitant with increasing age suggest that in spite of major differences in anatomy and physiology of the accommodative mechanism, chickens may become presbyopic. Results showing high amounts of nonmonotonic spherical aberration in hatchling lenses suggest inherently poor optics in these birds. PMID- 11773019 TI - Adaptations and deficits in the vestibulo-ocular reflex after sixth nerve palsy. AB - PURPOSE: The effects of paralytic strabismus on the vestibulo-ocular reflex (VOR) have not been systematically investigated in humans. The purpose of this study was to analyze the VOR in patients with unilateral peripheral sixth nerve palsy. METHODS: Twenty-one patients with unilateral peripheral sixth nerve palsy (6 severe, 7 moderate, 8 mild) and 15 normal subjects were studied. Subjects made sinusoidal +/-10 degrees head-on-body rotations in yaw and pitch at approximately 0.5 and 2 Hz, and in roll at approximately 0.5, 1, and 2 Hz. Eye movement recordings were obtained using magnetic scleral search coils in each eye in darkness and during monocular viewing in light. Static torsional VOR gains, defined as change in torsional eye position divided by change in head position during sustained head roll, were also measured. RESULTS: In all patients, horizontal VOR gains in darkness were decreased in the paretic eye in both abduction and adduction, but remained normal in the nonparetic eye in both directions. In light, horizontal visually enhanced VOR (VVOR) gains were normal in both eyes in moderate and mild palsy. In severe palsy, horizontal VVOR gains remained low in the paretic eye during viewing with either eye, whereas those in the nonparetic eye were higher than normal when the paretic eye viewed. Vertical VOR and VVOR were normal, but dynamic and static torsional VOR and VVOR gains were reduced in both eyes in all patients. CONCLUSIONS: In darkness, horizontal VOR gains were reduced during abduction of the paretic eye in all patients, as anticipated in sixth nerve palsy. Gains were also reduced during adduction of the paretic eye, suggesting that innervation to the medial rectus has changed. After severe palsy, vision did not increase abducting or adducting horizontal VVOR gains to normal in the paretic eye, but caused secondary increase in VVOR gains to values above unity in the nonparetic eye, when the paretic eye fixated. In mild and moderate palsy, vision enhanced the VOR in the paretic eye but caused no change in the nonparetic eye, suggesting a monocular readjustment of innervation selectively to the paretic eye. Vertical VOR and VVOR gains were normal, indicating that the lateral rectus did not have significant vertical actions through the excursions that we tested (+/-10 degrees ). Reduced torsional VOR gains in the paretic eye can be explained by the esotropia in sixth nerve palsy. Torsional VOR gain normally varies with vergence. We attribute the reduced torsional gains in the paretic eye to the mechanism that normally lowers it during convergence. The low torsional gains in the nonparetic eye may be an adaptation to reduce torsional disparity between the two eyes. PMID- 11773020 TI - Adaptive neural mechanism for Listing's law revealed in patients with sixth nerve palsy. AB - PURPOSE: During fixation and saccades, human eye movements obey Listing's law, which specifies the torsional eye position for each combination of horizontal and vertical eye positions. To study the mechanisms that implement Listing's law, the authors measured whether the law was violated in peripheral and central unilateral sixth nerve palsy. METHODS: Twenty patients with peripheral (13 chronic, 7 acute) sixth nerve palsy, 7 patients with central sixth nerve palsy caused by brainstem lesions, and 10 normal subjects were studied with scleral search coils. With the head immobile, subjects made saccades to a target that moved between straight ahead and eight eccentric positions. At each target position, fixation was maintained for 3 seconds before the next saccade. To quantify violations of Listing's law, we measured ocular torsion during fixation and during saccades, and compared it with the torsion predicted by the law. The SD of the differences between the predicted and measured torsion was called Listing deviation. RESULTS: Patients with central sixth nerve palsy had abnormal ocular torsion in both the paretic and nonparetic eyes, which violated Listing's law. During fixation, Listing deviation averaged 2.4 degrees in the paretic eye and 1.7 degrees in the nonparetic eye, compared with 0.8 degrees in normal control subjects (P < 0.05). During saccades, the Listing deviation averaged 2.7 degrees in the paretic eye, and 1.6 degrees in the nonparetic eye, compared with 0.8 degrees in normal control eyes (P < 0.05). Donders' law was also violated in both eyes of patients with central sixth nerve palsy. They showed an abnormally wide range of ocular torsion in any given gaze direction. In contrast, patients with acute peripheral palsy had abnormal ocular torsion only in the paretic eye. Listing deviation of the paretic eye averaged 2.3 degrees during fixation and 3.2 degrees during saccades (P < 0.05). Donders' law was obeyed in acute peripheral palsy. Patients with chronic peripheral sixth nerve palsy obeyed Listing's and Donders' laws during both fixation and saccades. CONCLUSIONS: Patients with central unilateral sixth nerve palsy have abnormal ocular torsion in both eyes, demonstrating that brainstem circuits normally participate in the maintenance of Listing's law. Eye movements in patients with acute peripheral sixth nerve palsy violate Listing's law, whereas those in patients with chronic peripheral palsy obey it, indicating that neural adaptation can restore Listing's law, even when the eye muscle remains abnormal. PMID- 11773021 TI - Macroglial alterations after isolated optic nerve sheath fenestration in rabbit. AB - PURPOSE: To study the modifications undergone by the macroglial cells after meningeal breach of the optic nerve in the rabbit, without optic neuropathy. METHODS: The optic nerve sheath fenestration technique carried out in humans was adapted to rabbit without axonal injury in the optic nerve. The effects of meningeal fenestration on glial cells were examined by immunocytochemical procedures (day 15) using the antibodies against two astrocyte markers: glial fibrillary acidic protein (GFAP) and vimentin. Proliferation of glial cells was evaluated with single 5-bromodeoxyuridine (BrdU) labeling or double GFAP and BrdU labelings. Qualitative data on glial cells were evaluated with the electron microscope. RESULTS: Optic nerve sheath fenestration on healthy adult rabbits resulted in a decrease of volume of the subarachnoid space located at the level of the meningeal scar, with a significant increase of the optic nerve area. The meninges presented a fibrous scar. In the optic nerve parenchyma, astrocytes appeared hypertrophic in the vicinity of the fenestration. The whole nerve contains numerous BrdU-labeled mitotic cells, a number of which double-labeled for both BrdU and GFAP belong to the astrocyte line. There was no loss of optic nerve axons. CONCLUSIONS: The inflammation produced by the surgical breach of the peri-optic meningeal sheaths induces a significant reactivity, including proliferation of astrocytes in the optic nerve. Reactive astrocytes may interact positively with axons and may modify the extracellular environment in the optic nerve. PMID- 11773022 TI - Response time as a discriminator between true- and false-positive responses in suprathreshold perimetry. AB - PURPOSE: To report on differences between the latency distributions of responses to stimuli and to false-positive catch trials in suprathreshold perimetry. To describe an algorithm for defining response time windows and to report on its performance in discriminating between true- and false-positive responses on the basis of response time (RT). METHODS: A sample of 435 largely inexperienced patients underwent suprathreshold visual field examination on a perimeter that was modified to record RTs. Data were analyzed from 60,500 responses to suprathreshold stimuli and from 523 false-positive responses to catch trials. RESULTS: False-positive responses had much more variable latencies than responses to suprathreshold stimuli. An algorithm defining RT windows on the basis of z transformed individual latency samples correctly identified more than 70% of false-positive responses to catch trials, whereas fewer than 3% of responses to suprathreshold stimuli were classified as false-positive responses. CONCLUSIONS: Latency analysis can be used to detect a substantial proportion of false-positive responses in suprathreshold perimetry. Rejection of such responses may increase the reliability of visual field screening by reducing variability and bias in a small but clinically important proportion of patients. PMID- 11773023 TI - Aqueous humor in primary open-angle glaucoma contains an increased level of CD44S. AB - PURPOSE: To determine whether the cell adhesion molecule CD44, the principal receptor of hyaluronan, is altered in the aqueous humor and the anterior segment of patients with primary open-angle glaucoma (POAG). METHODS: The trabecular meshwork (TM), iris, ciliary body, and sclera of POAG and age-matched control eyes preserved in ethanol were microdissected and subjected to 1% Triton X-100 solubilization at 4 degrees C. Western blot analysis was performed using monoclonal antibodies that recognize either CD44H (hematopoietic; extracellular domain) or CD44S (soluble ectodomain). The concentration of soluble CD44S in aqueous and microdissected tissues was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA of soluble CD44S of aqueous from eyes of patients with POAG indicated that the concentration of soluble CD44S is increased in comparison with that of aqueous from normal eyes (P < 0.0003). Western blot analysis and densitometry of POAG iris and ciliary body revealed a statistically significant increase in the Triton X-100 extraction of CD44H. The predominant increases were in the 180-kDa (P < 0.001) and the 85-kDa (P < 0.001) forms. ELISA of soluble CD44S indicated that the concentration is statistically decreased in iris (P < 0.05), ciliary body (P < 0.001), and TM (P < 0.005) of POAG eyes. CONCLUSIONS: Increased amounts of soluble CD44S in POAG aqueous and Triton X-100 solubilized CD44H characterized POAG in the iris and ciliary body. These soluble CD44 isoforms may influence the activity of the transmembrane CD44H by acting as inhibitors of CD44H and, thereby, adversely influence the cell survival of TM and retinal ganglion cells in POAG. PMID- 11773024 TI - Comparison of optic nerve imaging methods to distinguish normal eyes from those with glaucoma. AB - PURPOSE: To compare the ability of qualitative assessment of optic nerve head stereophotographs (ONHPs), confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to distinguish normal eyes from those with early to moderate glaucomatous visual field defects. METHODS: Eighty-nine eyes (63 normal, 63 age-matched with glaucoma) of 89 subjects more than 40 years of age were studied. Receiver operating characteristic (ROC) curves were generated from discriminant analysis of CSLO, SLP, and OCT measurements and from ONHP scores. Sensitivity at 80% and specificity at 90% were calculated. Differences between individual methods and combinations of methods were assessed for statistical significance. Agreement on categorization between methods (kappa) was assessed. RESULTS: The average visual field mean deviation (MD +/- SD) in patients with glaucoma was -3.9 +/- 2.2 dB, and the average pattern standard deviation (PSD) was 4.7 +/- 3.4 dB. In normal subjects the average MD was 0.1 +/- 0.9 dB and the average PSD was 1.5 +/- 0.3 dB. Optimal sensitivities, specificities, and areas under ROC curves were, respectively: ONHP (0.94, 0.87, 0.93), CSLO (0.84, 0.90, 0.92), SLP (0.89, 0.87, 0.94), and OCT (0.82, 0.84, 0.88). Best agreement on categorization (kappa) was between ONHPs and CSLO (0.70). The ROC area for the combination of methods was 0.99, higher than for any method alone. The ROC area for the combination of methods was significantly better than the CLSO rim area (P = 0.012) and the OCT retinal nerve fiber layer (RNFL) thickness (P = 0.002). CONCLUSIONS: The quantitative methods CSLO, SLP, and OCT were no better than qualitative assessment of disc ONHPs by experienced observers at distinguishing normal eyes from those with early to moderate glaucoma. A combination of the imaging methods significantly improves this capability. PMID- 11773025 TI - Reduction of intraocular pressure in mouse eyes treated with latanoprost. AB - PURPOSE: To determine whether topical treatment of mouse eyes with latanoprost alters intraocular pressure (IOP). METHODS: In a masked study design, NIH Swiss mice received a 2-microL topical instillation of 0.00015%, 0.0006%, 0.0025%, or 0.01% latanoprost or vehicle (phosphate-buffered saline [PBS]). After 1, 2, or 3 hours, the animals were anesthetized, and a fluid-filled glass microneedle connected to a pressure transducer was inserted through the cornea into the anterior chamber to measure IOP. The reduction of IOP after latanoprost measurement was calculated by the comparison between treated and nontreated eyes in the same mouse. The effect of latanoprost after a single 0.01% dose was also measured at 6, 12, and 24 hours. As in the previous study, the identity of all eye drop solutions was masked. RESULTS: In mouse eyes receiving topical PBS, the mean IOP was 14.8 +/- 2.2 mm Hg (n = 173 males). There was no significant difference in IOP between male and female eyes and between right and left eyes. At 1 hour after topical treatment with 0.00015% or 0.0025% latanoprost, IOP increased by as much as 11% +/- 7%. At 2 and at 3 hours after application, IOP decreased in a dose-dependent manner. These decreases were significant in eyes receiving 0.0025% or 0.01% latanoprost (P < 0.05, Student-Newman-Keuls test) and the largest decrease (14% +/- 8%) was noted 2 hours after treatment with 0.01% latanoprost. At 6, 12, or 24 hours after treatment, there was no difference in latanoprost- and PBS-treated eyes. CONCLUSIONS: Latanoprost reduces mouse IOP in a dose-dependent manner. The mouse may be a useful model for studying the effect of drugs on IOP. PMID- 11773026 TI - In vitro localization of TIGR/MYOC in trabecular meshwork extracellular matrix and binding to fibronectin. AB - PURPOSE: To determine whether trabecular meshwork-inducible glucocorticoid response/myocilin (TIGR/MYOC) protein associates with the extracellular matrix (ECM) of human trabecular meshwork (HTM) cells. METHODS: The extracellular localization of TIGR/MYOC was examined by immunofluorescence microscopy in HTM cultures treated with and without dexamethasone and ascorbate and in a transformed HTM cell line, TM-1, transiently transfected with TIGR/MYOC cDNA. Antibodies to TIGR/MYOC, fibronectin, laminin, type IV collagen, or thrombospondin were used to determine the extracellular localization of TIGR/MYOC. Solid phase binding assays using 125I-recombinant TIGR/MYOC and types I and IV collagens, fibronectin, and laminin were done to examine the association of TIGR/MYOC with these proteins and to identify a specific TIGR/MYOC binding site within fibronectin. The domains of fibronectin tested were the fibrin/collagen binding domain, the RGD domain, and the Heparin II (Hep II) domain. RESULTS: TIGR/MYOC colocalized with fibronectin, laminin, and type IV collagen, but not thrombospondin in both dexamethasone and dexamethasone/ascorbate-treated HTM cultures and in TM-1 cultures transfected with TIGR/MYOC cDNA. In solid phase binding assays, 125I-TIGR/MYOC bound fibronectin but not laminin or type IV collagen. Binding to fibronectin could be competed with excess TIGR/MYOC or fibronectin. Specific binding was found for the Hep II domain of fibronectin. CONCLUSIONS: TIGR/MYOC can associate with components of the ECM via interactions with the Hep II domain of fibronectin. The interactions with the Hep II domain of fibronectin could alter cell-matrix interactions in the TM and provides an interesting lead to explore the role(s) of TIGR/MYOC in both steroid-induced and primary open angle glaucoma. PMID- 11773027 TI - Comparing machine learning classifiers for diagnosing glaucoma from standard automated perimetry. AB - PURPOSE: To determine which machine learning classifier learns best to interpret standard automated perimetry (SAP) and to compare the best of the machine classifiers with the global indices of STATPAC 2 and with experts in glaucoma. METHODS: Multilayer perceptrons (MLP), support vector machines (SVM), mixture of Gaussian (MoG), and mixture of generalized Gaussian (MGG) classifiers were trained and tested by cross validation on the numerical plot of absolute sensitivity plus age of 189 normal eyes and 156 glaucomatous eyes, designated as such by the appearance of the optic nerve. The authors compared performance of these classifiers with the global indices of STATPAC, using the area under the ROC curve. Two human experts were judged against the machine classifiers and the global indices by plotting their sensitivity-specificity pairs. RESULTS: MoG had the greatest area under the ROC curve of the machine classifiers. Pattern SD (PSD) and corrected PSD (CPSD) had the largest areas under the curve of the global indices. MoG had significantly greater ROC area than PSD and CPSD. Human experts were not better at classifying visual fields than the machine classifiers or the global indices. CONCLUSIONS: MoG, using the entire visual field and age for input, interpreted SAP better than the global indices of STATPAC. Machine classifiers may augment the global indices of STATPAC. PMID- 11773028 TI - Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. AB - PURPOSE: Increased fibronectin accumulation in the trabecular meshwork of glaucomatous eyes may contribute to the resistance of aqueous outflow and the development of primary open-angle glaucoma (POAG). Because the glucose level is increased in the aqueous humor of patients with diabetes, this study was conducted to determine whether a high-glucose condition alters fibronectin expression and contributes to cell loss in trabecular meshwork. METHODS: The fibronectin mRNA level was determined using RT-PCR in bovine trabecular meshwork cells grown in normal (5 mM) or high (30 mM)-glucose medium for 7 days, and cell counts were measured during this period. Distribution and the relative amount of fibronectin protein were determined in these cells by immunofluorescence microscopy and Western blot analysis. RESULTS: Fibronectin mRNA level in cells grown in high-glucose medium was significantly upregulated two- to threefold compared with cells grown in normal medium (P < 0.05). In cells grown in high glucose medium, fibronectin immunofluorescence was more intense, and the relative amount of fibronectin protein was significantly increased (131% +/- 15% of control, P < 0.05) compared with the amount in cells grown in normal medium. A moderate decrease in cell number was observed in cells grown in high-glucose medium (78% +/- 7% of control, P < 0.05) CONCLUSIONS: These findings indicate that a high glucose level in aqueous humor of patients with diabetes may increase fibronectin syntheses and accumulation in trabecular meshwork and accelerate the depletion of trabecular meshwork cells, a characteristic feature of the outflow system in POAG. The striking similarity between high glucose-induced alterations in trabecular meshwork cells and those of vascular endothelial cells may represent a common biochemical link in the pathogenesis of POAG and diabetic microangiopathy. PMID- 11773029 TI - Protein interactions with myocilin. AB - PURPOSE: To identify factors that interact in vivo with myocilin, a glaucoma gene product. METHODS: The yeast two-hybrid system with myocilin as the bait and a human skeletal muscle cDNA library as the prey was used to identify potential factors that interact with myocilin. Interactions were also examined in bovine trabecular meshwork (TM) cells through a mammalian two-hybrid system. Biochemical coimmunoprecipitation from both human TM cell lysate and in vitro translated proteins was also used to confirm results obtained from yeast analysis. RESULTS: Twenty positive clones isolated through yeast two-hybrid screening were deemed potential myocilin partners. Sequence analysis determined that two of them encoded for myocilin from amino acids 64 to 268. Myocilin was also found to interact with a component of the myosin motor protein, myosin regulatory light chain (RLC). The myocilin-myocilin and myocilin-RLC interactions revealed by the yeast system were further confirmed and demonstrated in cultured TM cells, by means of a mammalian two-hybrid system, and through biochemical coimmunoprecipitation, subcellular fractionation, immunofluorescence, and immunogold double labeling. CONCLUSIONS: These results indicate that myocilin can form homomultimers in vivo, independent of the olfactomedin-like domain. Further analysis established that the leucine zipper motif of myocilin may be necessary for the myocilin-RLC interaction. The interaction of myocilin with RLC, a component of the myosin motor protein complex, implies a role for myocilin in the actomyosin system, linking in turn this novel protein to functional status of the TM. PMID- 11773030 TI - Characterization of the interleukin-4 receptor complex in human corneal fibroblasts. AB - PURPOSE: To characterize the interleukin (IL)-4 receptor (IL-4R) complex in human corneal fibroblasts. METHODS: The presence of IL-4R subunit mRNAs and proteins in cultured human corneal fibroblasts was examined by reverse transcription polymerase chain reaction and flow cytometry, respectively. The interaction of 125I-labeled IL-4 with specific cell surface receptors was characterized by saturation binding and Scatchard analysis. The effects of IL-4 on the tyrosine phosphorylation and subcellular localization of signal transducer and activator of transcription 6 (STAT6) were evaluated by immunoblot and indirect immunofluorescence analyses, respectively. The concentration of eotaxin in cell culture supernatant was measured by enzyme-linked immunosorbent assay. RESULTS: Transcripts encoding the IL-4R components IL-4Ralpha, IL-2Rgammac, IL-13Ralpha1, and IL-13Ralpha2 were detected in human corneal fibroblasts; IL-4Ralpha and IL 2Rgammac proteins were also expressed on the cell surface. The maximum number of IL-4 binding sites was 2.3 x 10(4) per cell, and the dissociation constant for the interaction of IL-4 with these sites was 10.1 +/- 0.3 pM. IL-4 induced tyrosine phosphorylation of STAT6 as well as translocation of this protein to the nucleus. Eotaxin release from corneal fibroblasts stimulated by the combination of IL-4 and tumor necrosis factor-alpha was inhibited by pretreatment of the cells with neutralizing antibodies to IL-4R. CONCLUSIONS: Cultured human corneal fibroblasts express high-affinity functional IL-4Rs on the cell surface, suggesting that these cells may contribute to the role of IL-4 as a key mediator of allergic reactions in the cornea. PMID- 11773031 TI - The role of Langerhans cells in Pseudomonas aeruginosa infection. AB - PURPOSE: Previous experimental studies have shown that extended-wear contact lens usage results in a centripetal migration of Langerhans cells from the conjunctiva into the central cornea. To test the consequences of this, Langerhans cells were induced into the cornea before Pseudomonas aeruginosa infection in BALB/c mice that are normally resistant (the cornea heals) and in C57BL/6 mice that are susceptible (the cornea perforates) to bacterial challenge. METHODS: Mean clinical scores, slit lamp examination, adenosine diphosphatase (ADPase), and acid phosphatase staining as well as immunostaining with DEC-205, B7-1, CD4, and interleukin-2 receptor (IL-2R) antibodies and histopathologic, RT-PCR, and delayed-type hypersensitivity (DTH) analyses were used to examine the effects on bacterial disease after polystyrene bead induction of Langerhans cells into the cornea before bacterial challenge. RESULTS: No difference in disease response was observed in bead- versus sham-treated C57BL/6 mice after bacterial infection; however, significant differences leading to corneal perforation were seen in BALB/c mice that included an increased number of Langerhans cells in the central cornea at 1 and 6 days after infection, an increased number of B7-1+ (mature) Langerhans cells at 6 days after infection, CD4+ and IL-2R+ T cells at 5 days after infection, enhanced DTH, and increased mRNA levels for IFN-gamma in cornea and cervical lymph nodes. Alternately, levels of IL-4 were significantly higher in the cornea and cervical lymph nodes of sham- versus bead-treated animals. CONCLUSIONS: These data provide evidence that Langerhans cells are critical in the innate immune response to P. aeruginosa and provide new information regarding the mechanisms governing resistance versus susceptibility to bacterial infection with this opportunistic pathogen. PMID- 11773032 TI - Decreased expression of ribosomal proteins in human age-related cataract. AB - PURPOSE: To identify lens epithelial genes with altered expression levels in age related human cataract. METHODS: Epithelia from age-related cataracts and from normal lenses were microdissected and RNA was extracted. RNAs were compared for gene expression differences by RT-PCR differential display. Transcripts exhibiting altered levels of gene expression were cloned and identified by sequencing. The expression levels of identified clones were confirmed by semiquantitative RT-PCR with three separately isolated RNA preparations. Specific primers were designed and used to examine the mRNA levels of other genes important in protein synthesis. RESULTS: Numerous transcripts exhibited altered levels of gene expression. One transcript exhibiting a decreased level of expression in cataract compared with normal lenses was identified as encoding ribosomal protein L21. Three additional ribosomal proteins, L15, L13a, and L7a, also exhibited decreased expression in cataract compared with normal human lenses. By contrast, the levels of elongation factor (EF)-1alpha1 and eucaryotic initiation factor (eIF)-4E remained unchanged. CONCLUSIONS: The results provide evidence that human age-related cataract is associated with decreased expression of L21 and other ribosomal proteins. The results suggest that modulation of protein synthesis and/or other functions mediated by ribosomal proteins is associated with age-related cataract. PMID- 11773033 TI - Lens proteomics: the accumulation of crystallin modifications in the mouse lens with age. AB - PURPOSE: To identify modified crystallins associated with aging of lens and produce two-dimensional electrophoresis (2-DE) proteome maps of crystallins in mouse lens. METHODS: Lens proteins from mice of increasing age or different strains were separated by either chromatography or 2-DE. Masses of whole proteins or tryptic peptides were analyzed by mass spectrometry. Changes in the abundance of individual crystallins were determined by image analysis of 2-DE gels. RESULTS: The measured masses of all known mouse crystallins, with the exception of gammaD and gammaF, matched the masses calculated from their reported sequences. Analysis by 2-DE indicated that most posttranslational modifications took place in mice after 6 weeks of age. Partially degraded crystallins, including betaB1, betaB2, betaB3, betaA3, alphaA, and alphaB, were found in greater proportion in the insoluble fractions. gamma-Crystallins A through F also became insoluble during aging. However, insolubilization of gamma-crystallins was associated with a decrease in isoelectric point (pI). Aging was also associated with increased phosphorylation of soluble alphaA- and alphaB-crystallins, confirmed by mass measurements of these proteins eluted from 2-DE gels. Comparison of protein profiles between several strains of mice used to produce transgenic or knockout models of cataract indicated few differences, except for an additional acidic form of a gamma-crystallin, possibly due to a polymorphism. CONCLUSIONS: These results suggest that partial degradation of alpha- and beta crystallins and increased acidity of gamma-crystallins may cause insolubilization during aging. The 2-DE proteome maps of mouse lens proteins created in this study, using immobilized pH gradients, will be useful for comparison with maps of lens proteins of mice with cataracts so that cataract-specific modifications may be identified. PMID- 11773034 TI - Lens proteomics: analysis of rat crystallin sequences and two-dimensional electrophoresis map. AB - PURPOSE: To determine the sequence of four rat beta-crystallins, confirm the sequences by mass spectrometry, and produce a two-dimensional electrophoresis (2 DE) map of soluble crystallins in young rat lens. METHODS: New or additional sequences were determined for betaB1, betaB3, betaA3, and betaA4-crystallin cDNAs from Sprague-Dawley rats, and the deduced protein sequences confirmed by mass spectrometry. The identity and relative abundance of each crystallin was then determined by 2-DE of soluble protein from whole lenses of 12-day-old rats, image analysis, and tandem mass spectrometry (MS/MS) spectra of peptides from in-gel digests. RESULTS: The previously unreported sequence of rat betaA4 cDNA encoded a 195-amino-acid protein. Additional cDNA sequencing provided the previously unknown N-terminal sequence of rat betaA3, found two differences from the previous amino acid sequences of both rat betaB1 and betaB3, and detected a polymorphism at residue 54 in rat betaB3. These new sequences were then confirmed by whole protein masses and MS/MS spectra of proteolytic digests. 2-DE analysis provided a more detailed map of rat crystallins than previously available and allowed the composition of crystallins in young rat lens to be compared with that in young human lens. CONCLUSIONS: This report provides baseline data that will facilitate the analysis of posttranslational modifications in rat crystallins during cataract. Detection of a polymorphism in the sequence of rat betaB3 suggests that crystallins in humans could also exhibit polymorphisms. The unusual abundance of rat betaB3 and low abundance of betaB2 may account for the increased susceptibility of rat crystallins to insolubilization during aging and cataract. PMID- 11773035 TI - Unexpected variation in unique features of the lens-specific type I cytokeratin CP49. AB - PURPOSE: CP49 is a fiber cell-specific type I cytokeratin, but its function as part of the fiber cell-beaded filament remains unknown. To provide a rational basis for mutational studies that would contribute to an elucidation of function, the study was designed to define elements of CP49s that are highly conserved, discriminate conserved features from species-specific variations, and identify where CP49s have diverged from consensus type I features in their adaptation to selective pressures in the lens. METHODS: The primary sequence and gene structure of CP49 from a third vertebrate order was determined from a combination of cDNA and genomic sequencing. Protein product was characterized by SDS-PAGE and Western blot analysis. Consensus features and phylogenetic relationships were identified by multiple alignment. Coiled-coil analysis was conducted to define central rod domains. RESULTS: Trout CP49 is unique among CP49s in having a 39-amino-acid tail domain and shows both unique sequence and allelic variation at the LNDR motif. Comparison of consensus sequences identified unprecedented divergence between CP49s and other type I cytokeratins, including a shortened central rod domain that is conserved among CP49s, but distinct from type I cytokeratins. CONCLUSIONS: The considerable differences that have emerged between the consensus features of the type I cytokeratins and the CP49s suggest that the beaded filament serves a significantly different function from intermediate filaments in other epithelia and that type I cytokeratins may have limited utility as a model for studies on lens beaded filaments. These differences, in concert with consensus features identified among CP49s, suggest sites that are probably critical to CP49 function in the lens fiber cell. PMID- 11773036 TI - A 6-bp deletion in the Crygc gene leading to a nuclear and radial cataract in the mouse. AB - PURPOSE: A mouse mutant expressing a bilateral nuclear and radial cataract was found after paternal treatment with chlorambucil. The purpose of this study was to establish the linkage of the mutation to a particular chromosome to allow molecular characterization. Moreover, the mutants were examined morphologically. METHODS: Isolated lenses were photographed and histologic sections of the eye were analyzed according to standard procedures. The mutation was localized to chromosome 1 by allelism testing with the Cryge(nz) mutation. Candidate genes were amplified by PCR from cDNA or genomic DNA and sequenced. RESULTS: A novel mouse cataract was characterized by a nuclear and radial opacification of the lens. The lenses of the mutants are smaller than those of the wild type. The histologic analysis demonstrated degeneration of lens fibers in the lens core. Abnormal remnants of cell nuclei are present throughout the entire lens. Genetic analysis revealed allelism to the Cat2 group of dominant cataracts on mouse chromosome 1; therefore, the cluster of the Cryg genes and the closely linked Cryba2 gene were tested as candidates. A 6-bp deletion in exon 3 of the gammaC crystallin encoding gene (Crygc) is causative for the cataract phenotype; the mutation is therefore designated CrygcChl3. The deletion of the bases 420 to 425 leads to a loss of two amino acids, Gly and Arg, in the fourth Greek-key motif. CONCLUSIONS: The CrygcChl3 is the first mutation in the mouse affecting the Crygc gene. Dominant mutations for five of the six Cryg genes on mouse chromosome 1 have now been characterized, demonstrating the importance of this gene cluster for lens transparency. PMID- 11773037 TI - Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography. AB - PURPOSE: To compare retinal thickening in diabetic macular edema assessed subjectively by evaluation of stereo fundus photographs with that assessed objectively by optical coherence tomography (OCT). METHODS: Forty-degree stereo fundus photographs of the macular field and OCT scans in 84 eyes of 47 patients with diabetes were compared in terms of both location and area of retinal thickening. Six radiating 6-mm OCT scans at intervals of 30 degrees were obtained, and the retinal thickness was compared with the mean retinal thickness +/- 2 SD of healthy control subjects (33 eyes). Subsequently, retinal thickness was mapped topographically and the subjectively assessed retinal thickening map was overlaid. The degree of agreement on location was evaluated as retinal thickening present or absent in nine subfields of the fundus. Area of retinal thickening was divided into four categories: no retinal thickening, less than 1 disc area (DA), less than 2 DAs, or less than 3 DAs, expressed as the kappa statistic. RESULTS: Exact agreement on location was found in 676 of 756 (84 x 9) observations (89.4%; kappa = 0.69; 95% confidence interval [CI]: 0.63-0.75). Two eyes in which both methods assessed the same amount of retinal thickening showed no agreement on location. These eyes were compared only in terms of location. Exact agreement on area was found in 69 (84.1%) of 82 eyes. Weighted kappa (kappa(w)) = 0.79; 95% CI: 0.76-0.82). CONCLUSIONS: The degree of agreement between subjectively and objectively assessed retinal thickening was very good, implying that changes in diabetic macular edema can be accurately and prospectively measured with OCT. PMID- 11773038 TI - Defocus-induced changes in ZENK expression in the chicken retina. AB - PURPOSE: To characterize the visual stimuli that control the expression of the transcription factor ZENK in glucagon-immunoreactive amacrine cells of the chicken retina. ZENK was previously found to change in correlation with the sign (+ or -) of imposed defocus, making it a potential candidate for regulation of the synthesis of growth factors involved in emmetropization. METHODS: Chicks were unilaterally treated with positive or negative lenses from 40 minutes to 2 hours. They were either kept in their cage environment (1000 lux) or in a large hemispheric dome under more homogeneous illumination (300 lux) in white or quasimonochromatic light (555 nm). In another experiment they were permitted only one viewing distance. ZENK expression was quantified in glucagon amacrine cells after the different treatments by means of double staining and cell counting. RESULTS: In all conditions tested, the number of ZENK-expressing cells was increased with positive lenses and reduced with negative lenses after only 40 minutes of exposure. If only one viewing distance was possible, the level of ZENK still responded to the sign of imposed defocus, although it required 80 minutes of treatment. In this experiment, the interocular difference was largely produced by changes in the contralateral control eyes rather than the lens-treated eyes. Finally, changes in ZENK expression appeared to be related to lens powers with a sigmoidal function, with saturation at approximately +7 D and -7 D of defocus, respectively. CONCLUSIONS: The results confirm that changes in ZENK expression are selective for the sign of imposed defocus. They may be independent of illuminance and do not require chromatic cues or variable viewing distances. The pathways for the substantial interactions between both eyes are not clear at present. PMID- 11773039 TI - Intravitreal delivery of oligonucleotides by sterically stabilized liposomes. AB - PURPOSE: The efficacy of sterically stabilized liposomes for delivering a model phosphodiester oligonucleotide intravitreally was investigated in the rabbit. METHODS: Ocular distribution and clearance from the vitreous humor of a model 16 mer oligothymidylate (pdT16) were evaluated in the rabbit by radioactivity measurements after intravitreal injection of either a solution or liposomes containing the [33P]pdT16 oligonucleotide. The integrity of pdT16 was investigated using a competitive hybridization assay. RESULTS: The residual concentration of the [33P]pdT16 oligonucleotide within the ocular tissues was significantly increased after intravitreal administration of the liposomal suspension compared with a simple solution. Administration of liposome encapsulated pdT16 oligonucleotide resulted in sustained release into the vitreous and the retina-choroid compared with release from the solution and in a reduced distribution to nontarget tissues (sclera, lens). In addition, liposomes protected the phosphodiester oligonucleotide against degradation. This was not observed after administration of the free oligonucleotide. CONCLUSIONS: The intravitreal injection of a phosphodiester oligonucleotide encapsulated within liposomes is a new way of delivering intact oligonucleotide to the eye in a controlled manner. This offers interesting prospects for the treatment of retinal diseases. PMID- 11773040 TI - Regulation of matrix metalloproteinase expression by tumor necrosis factor in a murine model of retinal neovascularization. AB - PURPOSE: Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through the regulation of extracellular proteinase production. It has been shown that matrix metalloproteinases (MMPs) are elevated in the retina during the neovascularization process. However, the factors and mechanisms that regulate the expression of these enzymes are not well characterized. The present study examines the potential role of tumor necrosis factor (TNF)-alpha as a regulator of MMPs in the retinal neovascularization process. METHODS: C57/Bl6 mice were treated with 75% oxygen (experimental) or room air (control) from postnatal days (P)7 through P12, followed by room air until P17. Retinas were collected at P13, P15, or P17 and total RNA analyzed for the relative level of TNFalpha, TNF receptor (p55), and TNFalpha-converting enzyme (TACE). Immunostaining was used to identify changes in TNF protein expression as well as to localize TNFalpha within specific retinal cell types. The role of TNFalpha in stimulating retinal microvascular endothelial cell (RMVEC) proteinase production was evaluated using isolated murine RMVECs grown in normoxic or hypoxic conditions. Message expression was analyzed by RT-PCR and protein expression by zymographic analysis. RESULTS: TNFalpha mRNA was increased in the retinas of experimental animals on P13 and P15, during the early stages of retinal neovascularization. In addition to being expressed by Muller glial cells and the inner nuclear layer, additional expression was noted in the outer nuclear layer of experimental animals. No significant level of apoptosis was detected in the retina of experimental animals with retinal neovascularization. Isolated RMVECs did not significantly increase MMP production directly in response to a hypoxic stimulus, but required the presence of exogenous TNFalpha. TNFalpha increased the expression of MT1-MMP, MMP-3, and MMP-9 in these cells. The levels of TACE and p55, proteins important in mediating the response of cells to TNFalpha, were found to be increased by the angiogenic protein, vascular endothelial growth factor (VEGF), which was also elevated in the experimental retinas. CONCLUSIONS: TNFalpha levels increase in experimental mouse retinas exposed to hypoxic stimuli. Increased production of MMPs by RMVECs does not occur directly in response to a hypoxic stimulus. These cells are responsive, however, to stimulation by TNFalpha, which enhances the production of specific members of the MMP family. VEGF also plays a role in this process through its regulation of TACE and p55 mRNA in the vascular endothelial cells. These findings support the hypothesis that these two growth factors have a role in the regulation of extracellular proteinase expression during retinal neovascularization. PMID- 11773041 TI - Phenotypic variation of retinal pigment epithelium in age-related macular degeneration. AB - PURPOSE: To determine whether retinal pigment epithelium (RPE) in eyes with age related macular degeneration (ARMD) express vimentin and alpha smooth muscle actin (alphaSMA), two cytoskeletal proteins associated with phenotypic variation in culture. METHODS: Six eyes with late ARMD and three age-matched control eyes were preserved in buffered 4% paraformaldehyde and cryosectioned at 10 microm. Stages of RPE morphology and pigmentation were assessed by the Alabama Age Related Macular Degeneration Grading System. Vimentin, alphaSMA, and glial fibrillary acidic protein (GFAP) expression was detected by indirect immunofluorescence. These results were compared with regional variations in disease severity. RESULTS: RPE changes in ARMD included acquired expression of vimentin, but alphaSMA-positive cells were rare. GFAP expression increased in Muller cells in the neural retina in association with RPE changes and photoreceptor degeneration. CONCLUSIONS: The initial stages of RPE changes in eyes with ARMD mimic those reported for cultured RPE cells. The absence of alphaSMA-positive cells in regions of RPE atrophy suggests that RPE are lost rather than persist in a dedifferentiated state. PMID- 11773042 TI - Retinal pigment epithelium of the rat express CD81, the target of the anti proliferative antibody (TAPA). AB - PURPOSE: The present study focuses on the role of CD81, the target of the anti proliferative antibody (TAPA), in the regulation of the growth of retinal pigment epithelium (RPE). METHODS: RPE of 8-day-old rat pups was cultured. The level of CD81 in the cultures was defined by immunoblot methods, and the distribution of the protein was examined using indirect immunohistochemical methods. In addition, the effects of the antibody binding were tested in culture. RESULTS: CD81 was found in all layers of the normal retina with a distinct absence of labeling in the inner and outer segments of the photoreceptors. Based on the authors' original immunohistochemical analysis, it was difficult to determine whether CD81 was expressed by RPE. By examining cultures of RPE it was demonstrated that CD81 was expressed on the surface of these cells and that it was concentrated at regions of cell-cell contact. Indirect immunohistochemical methods using a peroxidase-labeled secondary antibody in albino mice revealed heavy labeling of the RPE in the intact eye. When the AMP1 antibody (directed against the large extracellular loop of CD81) was added to cultured RPE, the mitotic activity of the cells was depressed. CONCLUSIONS: CD81 was found in the normal rat retina. Previous studies demonstrated that CD81 was expressed in retinal glia, the Muller cells that span the thickness of the retina, and astrocytes found in the ganglion cell layer. The present study demonstrated that CD81 was also expressed by RPE. The dramatic effects of the AMP1 antibody and the location of CD81 at regions of cell-cell contact support the hypothesis that this molecule is part of a molecular switch controlling contact inhibition. PMID- 11773043 TI - Color matching in diabetes: optical density of the crystalline lens and macular pigments. AB - PURPOSE: To measure the optical density of the crystalline lens and macular pigments in a group of patients with diabetes mellitus and compare the results with those in a group of control subjects. METHODS: Color matches were performed using a Wright tristimulus colorimeter. The reference wavelength used was 490 nm, desaturated with 650 nm. Lens optical density was measured by mixing spectral primaries of wavelengths 420, 515, and 650 nm to match the reference. Wavelengths 420 and 515 nm were chosen, because they are absorbed equally by the macular pigment. To measure macular pigment density, two color matches were performed, one foveal and one 5 degrees extrafoveal. The reference stimulus was matched by mixing spectral primaries of 460, 530, and 650 nm. The ratio of the foveal to extrafoveal color match gives the optical density of the macular pigment. Thirty four diabetic patients and 34 control subjects performed the lens density color match, and of these, 26 diabetic patients and 30 control subjects performed the macular pigment density color matches. RESULTS: There is a significant increase in the optical density of the lens in diabetes with age in comparison to the control subjects (P < 0.001), with a duration dependence of 0.02 log units/year. The mean macular pigment density in the diabetic patients was 0.13 +/- 0.20 log units and in the control subjects 0.32 +/- 0.24 log units (P = 0.0015). Patients with grade 2 maculopathy had significantly lower pigment density than those with no maculopathy (P = 0.016). CONCLUSIONS: The ocular media of diabetic persons are abnormal, with increased lens and reduced macular pigment optical density. The relationship between reduced macular pigment levels with increasing severity of maculopathy may implicate oxidative stress as a causative factor. PMID- 11773044 TI - 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosis. AB - Conformational diseases such as amyloidosis, Alzheimer's disease, prion diseases, and the serpinopathies are all caused by structural rearrangements within a protein that transform it into a pathological species. These diseases are typified by the Z variant of alpha(1)-antitrypsin (E342K), which causes the retention of protein within hepatocytes as inclusion bodies that are associated with neonatal hepatitis and cirrhosis. The inclusion bodies result from the Z mutation perturbing the conformation of the protein, which facilitates a sequential interaction between the reactive center loop of one molecule and beta sheet A of a second. Therapies to prevent liver disease must block this reactive loop-beta-sheet polymerization without interfering with other proteins of similar tertiary structure. We have used reactive loop peptides to explore the differences between the pathogenic Z and normal M alpha(1)-antitrypsin. The results show that the reactive loop is likely to be partially inserted into beta sheet A in Z alpha(1)-antitrypsin. This conformational difference from M alpha(1) antitrypsin was exploited with a 6-mer reactive loop peptide (FLEAIG) that selectively and stably bound Z alpha(1)-antitrypsin. The importance of this finding is that the peptide prevented the polymerization of Z alpha(1) antitrypsin and did not significantly anneal to other proteins (such as antithrombin, alpha(1)-antichymotrypsin, and plasminogen activator inhibitor-1) with a similar tertiary structure. These findings provide a lead compound for the development of small molecule inhibitors that can be used to treat patients with Z alpha(1)-antitrypsin deficiency. Furthermore they demonstrate how a conformational disease process can be selectively inhibited with a small peptide. PMID- 11773045 TI - Apolipoprotein A-I induces translocation of cholesterol, phospholipid, and caveolin-1 to cytosol in rat astrocytes. AB - Intercellular cholesterol transport in the brain is carried by high density lipoprotein (HDL) generated in situ by cellular interaction with the apolipoprotein apoE, which is mainly synthesized by astrocytes, and with apoA-I secreted by cells such as endothelial cells. Rat astrocytes in fact generate HDL with extracellular apoA-I in addition to releasing HDL with endogenously synthesized apoE, seemingly by the same mechanism as the HDL assembly for systemic circulation. Relating to this reaction, apoA-I induced translocation of newly synthesized cholesterol and phospholipid to the cytosol prior to extracellular assembly of HDL, accompanied by an increase of caveolin-1 in the cytosol, activation of sterol regulatory element-binding protein, and enhancement of cholesterol synthesis. The lipid translocated into the cytosol was recovered in the fraction with a density of 1.09-1.16 g/ml as well as caveolin-1 and cyclophilin A. Cyclosporin A inhibited these apoA-I-mediated reactions and suppressed apoA-I-mediated cholesterol release. The findings suggest that such translocation of cholesterol and phospholipid into the cytosol is related to the apo A-I-mediated HDL assembly in astrocytes through functional association with caveolin-1 and a cyclosporin A-sensitive cyclophilin protein(s). PMID- 11773046 TI - Two distinct proteolytic systems responsible for glucose-induced degradation of fructose-1,6-bisphosphatase and the Gal2p transporter in the yeast Saccharomyces cerevisiae share the same protein components of the glucose signaling pathway. AB - Addition of glucose to Saccharomyces cerevisiae inactivates the galactose transporter Gal2p and fructose-1,6-bisphosphatase (FBPase) by a mechanism called glucose- or catabolite-induced inactivation, which ultimately results in a degradation of both proteins. It is well established, however, that glucose induces internalization of Gal2p into the endocytotic pathway and its subsequent proteolysis in the vacuole, whereas FBPase is targeted to the 26 S proteasome for proteolysis under similar inactivation conditions. Here we report that two distinct proteolytic systems responsible for specific degradation of two conditionally short-lived protein targets, Gal2p and FBPase, utilize most (if not all) protein components of the same glucose sensing (signaling) pathway. Indeed, initiation of Gal2p and FBPase proteolysis appears to require rapid transport of those substrates of the Hxt transporters that are at least partially metabolized by hexokinase Hxk2p. Also, maltose transported via the maltose-specific transporter(s) generates an appropriate signal that culminates in the degradation of both proteins. In addition, Grr1p and Reg1p were found to play a role in transduction of the glucose signal for glucose-induced proteolysis of Gal2p and FBPase. Thus, one signaling pathway initiates two different proteolytic mechanisms of catabolite degradation, proteasomal proteolysis and endocytosis followed by lysosomal proteolysis. PMID- 11773047 TI - Sp3 represses gene expression via the titration of promoter-specific transcription factors. AB - We have determined previously that Sp3 encodes three distinct gene products as follows: a full-length protein (Sp3) that is an activator of transcription and two isoforms (M1 and M2) derived via internal translational initiation that function as transcriptional repressors. To identify amino acids and functions required for transcriptional repression, we employed PCR-directed mutagenesis to create a panel of mutated M2 proteins. Biochemical and functional analyses of these mutated proteins indicate that functions encoded by the M2 carboxyl terminus, such as DNA binding activity and the capacity to form multimeric complexes, are not required or sufficient for transcriptional repression. Instead, a 93-amino acid portion of the trans-activation domain was shown to be the minimal portion of M2 required to block Sp-dependent gene expression. Transcriptional analysis of three Sp-dependent promoters showed that mutations sustained by many M2 proteins result in promoter-specific effects. Regions of M2 required for physical interactions with five TATA box-associated factors (TAF(II)s) were mapped, and mutations that disrupt the interaction of M2 with two of these proteins, TAF(II)70 and TAF(II)40, were identified. We conclude that Sp3 mediated transcriptional repression is due, at least in part, to competition for promoter-specific transcription factors. PMID- 11773048 TI - The oligogalacturonate-specific porin KdgM of Erwinia chrysanthemi belongs to a new porin family. AB - The phytopathogenic Gram-negative bacteria Erwinia chrysanthemi secretes pectinases, which are able to degrade the pectic polymers of plant cell walls, and uses the degradation products as a carbon source for growth. We characterized a major outer membrane protein, KdgM, whose synthesis is strongly induced in the presence of pectic derivatives. The corresponding gene was characterized. Analysis of transcriptional fusions showed that the kdgM expression is controlled by the general repressor of pectinolytic genes, KdgR, by the repressor of hexuronate catabolism genes, ExuR, by the pectinase gene repressor, PecS, and by catabolite repression via the cyclic AMP receptor protein (CRP) transcriptional activator. A kdgM mutant is unable to grow on oligogalacturonides longer than trimers, and its virulence is affected. Electrophysiological experiments with planar lipid bilayers showed that KdgM behaves like a voltage-dependent porin that is slightly selective for anions and that exhibits fast block in the presence of trigalacturonate. In contrast to most porins, KdgM seems to be monomeric. KdgM has no homology with currently known porins, but proteins similar to KdgM are present in several bacteria. Therefore, these proteins might constitute a new family of porin channels. PMID- 11773049 TI - Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans as well as association with lipid microdomains. AB - The apical sorting of human intestinal dipeptidyl peptidase IV (DPPIV) occurs through complex N-linked and O-linked carbohydrates. Inhibition of O-linked glycosylation by benzyl-N-acetyl-alpha-d-galactosaminide affects significantly the sorting behavior of DPPIV in intestinal Caco-2 and HT-29 cells. However, random delivery to the apical and basolateral membranes and hence a more drastic effect on the sorting of DPPIV in both cell types is only observed when, in addition to O-glycans, the processing of N-glycans is affected by swainsonine, an inhibitor of mannosidase II. Together the data indicate that both types of glycosylation are critical components of the apical sorting signal of DPPIV. The sorting mechanism of DPPIV implicates its association with detergent-insoluble membrane microdomains containing cholesterol and sphingolipids, whereas an efficient association largely depends on the presence of a fully complex N- and O linked glycosylated DPPIV. Interestingly, cholesterol is a more critical component in this context than sphingolipids, because cholesterol depletion by beta-cyclodextrin affects the detergent solubility and the sorting behavior of DPPIV more strongly than fumonisin, an inhibitor of sphingolipid synthesis. PMID- 11773050 TI - Unusual polypeptide synthesis in the kinetoplast-mitochondria from Leishmania tarentolae. Identification of individual de novo translation products. AB - The de novo synthesis of cytochrome c oxidase subunits I, II (COI and COII), and apocytochrome b (Cyb) was investigated in kinetoplast-mitochondria of Leishmania. The organelles were isolated after breaking whole cells with nitrogen cavitation. Individual COI, COII, and Cyb polypeptides were identified by fractionation of the kinetoplast membranes, labeled with [(35)S]methionine and cysteine, using two dimensional (9 versus 14% and 20 versus 11%) denaturing gel electrophoresis. The reaction did not require exogenous energy sources or amino acids. On the contrary, the presence of amino acids other than methionine somewhat inhibited the labeling reaction probably by competing with the uptake of labeled amino acids. The synthesis reaction was insensitive to 100 microg/ml chloramphenicol, gentamycin, paromomycin, lincomycin, hygromycin, and tetracycline, as well as cycloheximide. The process showed a linear increase in the amount of synthesized polypeptides during the first 2 h of incubation, followed by a slower accumulation of products for up to 4 h. The de novo synthesized polypeptides were stable for several additional hours. Their assembly into respiratory complexes, investigated using two-dimensional Blue Native/N-[2-hydroxy-1,1 bis(hydroxymethyl)ethyl]glycine-SDS gels, began early during the incubation and continued throughout the course of the synthesis. This work represents the first unequivocal identification of the polypeptide synthesis in kinetoplasts. PMID- 11773051 TI - Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathways. AB - Activated Ras but not Raf can transform RIE-1 and other epithelial cells, indicating the critical importance of Raf-independent effector function in Ras transformation of epithelial cells. To elucidate the nature of these Raf independent activities, we utilized representational difference analysis to identify genes aberrantly expressed by Ras through Raf-independent mechanisms in RIE-1 cells. We identified a total of 22 genes, both known and novel, whose expression was either activated or abolished by Ras but not Raf. The genes up regulated encode proteins involved in protein or DNA synthesis, regulation of protease activity, or ligand binding, whereas those genes down-regulated encode actin cytoskeletal-, extracellular matrix-, and gap junction-associated proteins, and transmembrane receptor- or cytokine-like proteins. These results suggest that a key function of Raf-independent signaling involves deregulation of gene expression. We further characterized transgelin as a gene whose expression was abolished by Ras. Transgelin was identified previously as a protein whose expression was lost in virally transformed cell lines. We show that this loss is regulated at the level of gene expression and that both Raf-dependent and Raf independent pathways are required to cause Ras down-regulation of transgelin in RIE-1 cells, whereas Raf alone is sufficient to cause its loss in NIH 3T3 fibroblasts. We also found that Ras-dependent and Ras-independent mechanisms can cause the down-regulation of transgelin in human breast and colon carcinoma cells lines and patient-derived tumor samples. We conclude that loss of transgelin gene expression may be an important early event in tumor progression and a diagnostic marker for breast and colon cancer development. PMID- 11773052 TI - Drosophila Ack targets its substrate, the sorting nexin DSH3PX1, to a protein complex involved in axonal guidance. AB - Dock, the Drosophila orthologue of Nck, is an adaptor protein that is known to function in axonal guidance paradigms in the fly including proper development of neuronal connections in photoreceptor cells and axonal tracking in Bolwig's organ. To develop a better understanding of axonal guidance at the molecular level, we purified proteins in a complex with the SH2 domain of Dock from fly Schneider 2 cells. A protein designated p145 was identified and shown to be a tyrosine kinase with sequence similarity to mammalian Cdc-42-associated tyrosine kinases. We demonstrate that Drosophila Ack (DAck) can be co-immunoprecipitated with Dock and DSH3PX1 from fly cell extracts. The domains responsible for the in vitro interaction between Drosophila Ack and Dock were identified, and direct protein-protein interactions between complex members were established. We conclude that DSH3PX1 is a substrate for DAck in vivo and in vitro and define one of the major in vitro sites of DSH3PX1 phosphorylation to be Tyr-56. Tyr-56 is located within the SH3 domain of DSH3PX1, placing it in an important position for regulating the binding of proline-rich targets. We demonstrate that Tyr-56 phosphorylation by DAck diminishes the DSH3PX1 SH3 domain interaction with the Wiskott-Aldrich Syndrome protein while enabling DSH3PX1 to associate with Dock. Furthermore, when Tyr-56 is mutated to aspartate or glutamate, the binding to Wiskott-Aldrich Syndrome protein is abrogated. These results suggest that the phosphorylation of DSH3PX1 by DAck targets this sorting nexin to a protein complex that includes Dock, an adaptor protein important for axonal guidance. PMID- 11773053 TI - The activity of a developmentally regulated cysteine proteinase is required for cyst wall formation in the primitive eukaryote Giardia lamblia. AB - Giardia is an intestinal parasite that belongs to the earliest diverging branch of the eukaryotic lineage of descent. Giardia undergoes adaptation for survival outside the host's intestine by differentiating into infective cysts. Encystation involves the synthesis and transport of cyst wall constituents to the plasma membrane for release and extracellular organization. Nevertheless, little is known about the molecular events related to cyst wall biogenesis in Giardia. Among the components of the cyst wall there are two proteins that we have previously identified and characterized: CWP1 (26 kDa) and CWP2 (39 kDa). Expression of these proteins is coordinately induced, and both concentrated within encystation-specific secretory vesicles before their extracellular polymerization. Although highly similar to each other at the amino terminus, CWP2 includes a COOH-terminal 121-amino acid extension. Here, we show that this extension, rich in basic residues, is cleaved from CWP2 before cyst wall formation by an intracellular cysteine proteinase activity, which is induced during encystation like CWPs. Specific inhibitors prevent release of cyst wall materials, abolishing cyst wall formation. We also report the purification, cloning, and characterization of the encystation-specific cysteine proteinase responsible for the proteolytic processing of CWP2, which is homologue to lysosomal cathepsin C. Encystation-specific cysteine proteinase ESCP possesses unique characteristics compared with cathepsins from higher eukaryotes, such as a transmembrane domain and a short cytoplasmic tail. These features make this enzyme the most divergent cathepsin C identified to date and provide new insights regarding cyst wall formation in Giardia. PMID- 11773055 TI - Identification and functional analysis of the rat caspase-3 gene promoter. AB - Caspase-3 is the major effector in apoptosis triggered by various stimuli. Previous studies demonstrated a significant increase in transcriptional activity of the caspase-3 gene during neuronal apoptosis. Recent findings suggest that differential expression of the caspase-3 gene may underlie the regulation of apoptotic susceptibility during brain development and after acute injury to the mature brain. We identified and cloned the rat caspase-3 gene promoter, determined its structure, and examined its regulation during a course of apoptosis in PC12 cells. Results demonstrate that this promoter lacks a TATA-box and contains a cluster of Sp1 elements and multiple transcription start sites. The first identified transcription start site is located 87-bp upstream from the first splicing site. A role of Sp1 elements in the regulation of caspase-3 promoter activity is demonstrated by the inhibition of Sp1 binding using mithramycin A. Results of deletion analysis show that an Ets-1-like element located between nucleotides -1646 and -1632 relative to the most extended transcription start site is necessary to achieve sustained transcriptional activity. Homology analysis revealed that the 5'-flanking region of the human caspase-3 gene exhibits significant similarity to a regulatory region of the rat gene. PMID- 11773054 TI - Molecular basis of evolutionary loss of the alpha 1,3-galactosyltransferase gene in higher primates. AB - Galactose-alpha1,3-galactose (alphaGal) epitopes, the synthesis of which requires the enzyme product of alpha1,3-galactosyltransferase (alpha1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The alphaGal negative species as well as mice with deletion of the alpha1,3GT gene produce abundant anti-alphaGal antibodies. The evolutionary loss of alphaGal epitopes has been attributed to point mutations in the coding region of the gene. Because no transcripts could be found in the higher primate species with Northern blot analysis, a potential alternative explanation has been loss of upstream regulation of the gene. Here, we have demonstrated that the rhesus promoter is functional. More importantly, a variety of full-length transcripts were detected with sensitive PCR-based methods in the tissues of rhesus monkeys, orangutans, and humans. Five crucial mutations were delineated in the coding region of the human and rhesus and three in the orangutan, any one of which could be responsible for inactivation of the alpha1,3GT gene. Two of the mutations were shared by all three higher primates. These findings, which elucidate the molecular basis for the evolutionary loss of alphaGal expression, may have implications in medical research. PMID- 11773056 TI - Cloning and expression of a chloride-dependent Na+-H+ exchanger. AB - Electroneutral Na(+)-H(+) exchange is present in virtually all cells, mediating the exchange of extracellular Na(+) for intracellular H(+) and, thus, plays an important role in the regulation of intracellular pH, cell volume, and transepithelial Na(+) absorption. Recent transport studies demonstrated the presence of a novel chloride-dependent Na(+)-H(+) exchange in the apical membrane of crypt cells of rat distal colon. We describe the cloning of a 2.5-kb full length cDNA from rat distal colon that encodes 438 amino acids and has six putative transmembrane spanning domains. Of the 438 amino acids 375 amino acids at the N-terminal region are identical to Na(+)-H(+) exchange (NHE)-1 isoform with the remaining 63 amino acids comprising a completely novel C terminus. In situ hybridization revealed that this transcript is expressed in colonic crypt cells, whereas Northern blot analysis established the presence of its 2.5-kb mRNA in multiple tissues. Despite its much smaller size compared with all other known Na(+)-H(+) exchange isoforms, NHE-deficient PS120 fibroblasts stably transfected with this cDNA exhibited Na(+)-dependent intracellular pH recovery to an acid load that was chloride-dependent and inhibited both by 5-ethylisopropylamiloride, an amiloride analogue, and by 5'-nitro-2-(3-phenylproplyamino)benzoic acid, a Cl( ) channel blocker, but only minimally affected by 25 microm 3-methylsulfonyl 4piperidonbenzoylguanidine, an NHE-1 and NHE-2 isoform inhibitor. In contrast to other Na(+)-H(+) exchange isoforms in colonic epithelial cells, chloride dependent Na(+)-H(+) exchange mRNA abundance was increased by dietary sodium depletion. Based on these results we predict that chloride-dependent Na(+)-H(+) exchange represents a new class of Na(+)-H(+) exchangers that may regulate ion transport in several organs. PMID- 11773057 TI - Trafficking and cell surface stability of the epithelial Na+ channel expressed in epithelial Madin-Darby canine kidney cells. AB - The apically located epithelial Na(+) channel (alphabetagamma-ENaC) plays a key role in the regulation of salt and fluid transport in the kidney and other epithelia, yet its mode of trafficking to the plasma membrane and its cell surface stability in mammalian cells are poorly understood. Because the expression of ENaC in native tissues/cells is very low, we generated epithelial Madin-Darby canine kidney (MDCK) cells stably expressing alphabetagamma-ENaC, where each subunit is tagged differentially at the intracellular C terminus and the beta-subunit is also Myc-tagged at the ectodomain (alpha(HA)beta(Myc,T7)gamma(FLAG)). ENaC expression in these cells was verified by immunoblotting with antibodies to the tags, and patch clamp analysis has confirmed that the tagged channel is functional. Moreover, using electron microscopy, we demonstrated apical, but not basal, membrane localization of ENaC in these cells. The glycosylation pattern of the intracellular pool of ENaC revealed peptide N-glycosidase F and endoglycosidase H sensitivity. Surprisingly, the cell surface pool of ENaC, analyzed by surface biotinylation, was also core glycosylated and lacked detectable endoglycosidase H-resistant channels. Extraction of the channel from cells in Triton X-100 demonstrated that both intracellular and cell surface pools of ENaC are largely soluble. Moreover, floatation assays to analyze the presence of ENaC in lipid rafts showed that both intracellular and cell surface pools of this channel are not associated with rafts. We have shown previously that the total cellular pool of ENaC is turned over rapidly (t(1/2) approximately 1-2 h). Using cycloheximide treatment and surface biotinylation we now demonstrate that the cell surface pool of ENaC has a similarly short half-life (t(1/2) approximately 1 h), unlike the long half-life reported recently for the Xenopus A6 cells. Collectively, these results help elucidate key aspects of ENaC trafficking and turnover rates in mammalian kidney epithelial cells. PMID- 11773058 TI - Biochemical analysis of chromatin containing recombinant Drosophila core histones. AB - To investigate the effects of histone modifications upon chromatin structure and function, we studied the assembly and properties of chromatin that contains unmodified recombinant core histones. To this end, we synthesized the Drosophila core histones in Escherichia coli. The purified histones were lacking covalent modifications as well as their N-terminal initiating methionine residues. The recombinant histones were efficiently assembled into periodic nucleosome arrays in a completely purified recombinant system with Drosophila ATP-utilizing chromatin assembly and remodeling factor (ACF), Drosophila nucleosome assembly protein-1, plasmid DNA, and ATP. With the Gal4-VP16 activator and a crude transcription extract, we found that the transcriptional properties of ACF assembled chromatin containing unmodified histones were similar to those of chromatin containing native histones. We then examined ACF-catalyzed chromatin remodeling with completely purified factors and chromatin consisting of unmodified histones. In these experiments, we observed promoter-specific disruption of the regularity of nucleosome arrays upon binding of Gal4-VP16 as well as nucleosome positioning by R3 Lac repressor and subsequent nucleosome remobilization upon isopropyl-beta-D-thiogalactopyranoside-induced dissociation of R3 from the template. Thus, chromatin assembly and remodeling by ACF can occur in the absence of histone modifications. PMID- 11773059 TI - Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells. AB - Connective tissue growth factor (CTGF) is abundantly expressed in the vascular smooth muscle cells (VSMC) of atherosclerotic lesions but not in normal vessels. CTGF is able to promote VSMC proliferation and migration and influences the composition of extracellular matrix. The mechanisms for controlling these events remain unclear. We studied the effects of CTGF on matrix metalloproteinases (MMPs) by introducing a CTGF over-expression construct into VSMC. We found that the over-expression of CTGF significantly increased the activity of MMP-2 in VSMC conditioned medium. MMP-2 activity was similarly increased by exogenous CTGF treatment, and this effect could be blocked by an anti-CTGF antibody. We also showed that the increased MMP-2 activity was due to an increase in MMP-2 mRNA levels in VSMC. We further studied the mechanisms involved in the regulation of MMP-2 mRNA levels and found that the AP-2 transcription factor is responsible for most of the CTGF-induced MMP-2 transcription. Because MMP-2 is an important factor directly involved in controlling cell movement and the turnover of extracellular matrix, our study may provide a mechanism for CTGF-promoted VSMC migration. PMID- 11773060 TI - Genistein restores functional interactions between Delta F508-CFTR and ENaC in Xenopus oocytes. AB - The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its Cl(-) channel properties, has regulatory interactions with other epithelial ion channels including the epithelial Na(+) channel (ENaC). Both the open probability and surface expression of wild type CFTR Cl(-) channels are increased significantly when CFTR is co-expressed in Xenopus oocytes with alphabetagamma ENaC, and conversely, the activity of ENaC is inhibited following wild type CFTR activation. Using the Xenopus oocyte expression system, a lack of functional regulatory interactions between DeltaF508-CFTR and ENaC was observed following activation of DeltaF508-CFTR by forskolin and isobutylmethylxanthine (IBMX). Whole cell currents in oocytes expressing ENaC alone decreased in response to genistein but increased in response to a combination of forskolin and IBMX followed by genistein. In contrast, ENaC currents in oocytes co-expressing ENaC and DeltaF508-CFTR remained stable following stimulation with forskolin/IBMX/genistein. Furthermore, co-expression of DeltaF508-CFTR with ENaC enhanced the forskolin/IBMX/genistein-mediated activation of DeltaF508-CFTR. Our data suggest that genistein restores regulatory interactions between DeltaF508 CFTR and ENaC and that combinations of protein repair agents, such as 4 phenylbutyrate and genistein, may be necessary to restore DeltaF508-CFTR function in vivo. PMID- 11773061 TI - A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells. AB - Constitutive activation of NF-kappa B is an emerging hallmark of various types of tumors including breast, colon, pancreatic, ovarian, and melanoma. In melanoma cells, the basal expression of the CXC chemokine, CXCL1, is constitutively up regulated. This up-regulation can be attributed in part to constitutive activation of NF-kappa B. Previous studies have shown an elevated basal I kappa B kinase (IKK) activity in Hs294T melanoma cells, which leads to an increased rate of I kappa B phosphorylation and degradation. This increase in I kappa B-alpha phosphorylation and degradation leads to an approximately 19-fold higher nuclear localization of NF-kappa B. However, the upstream IKK kinase activity is up regulated by only about 2-fold and cannot account for the observed increase in NF kappa B activity. We now demonstrate that NF-kappa B-inducing kinase (NIK) is highly expressed in melanoma cells, and IKK-associated NIK activity is enhanced in these cells compared with the normal cells. Kinase-dead NIK blocked constitutive NF-kappa B or CXCL1 promoter activity in Hs294T melanoma cells, but not in control normal human epidermal melanocytes. Transient overexpression of wild type NIK results in increased phosphorylation of extracellular signal regulated kinases 1 and 2 (ERK1/2), which is inhibited in a concentration dependent manner by PD98059, an inhibitor of p42/44 MAPK. Moreover, the NF-kappa B promoter activity decreased with overexpression of dominant negative ERK expression constructs, and EMSA analyses further support the hypothesis that ERK acts upstream of NF-kappa B and regulates the NF-kappa B DNA binding activity. Taken together, our data implicate involvement of I kappa B kinase and MAPK signaling cascades in NIK-induced constitutive activation of NF-kappa B. PMID- 11773062 TI - Analysis of DsRed Mutants. Space around the fluorophore accelerates fluorescence development. AB - Earlier mutagenesis of the red fluorescent protein drFP583, also called DsRed, resulted in a mutant named Fluorescent Timer (Terskikh, A., Fradkov, A., Ermakova, G., Zaraisky, A., Tan, P., Kajava, A. V., Zhao, X., Lukyanov, S., Matz, M., Kim, S., Weissman, I., and Siebert, P. (2000) Science 290, 1585--1588). Further mutagenesis generated variants with novel and improved fluorescent properties. The mutant called AG4 exhibits only green fluorescence. The mutant, called E5up (V105A), shows complete fluorophore maturation, eventually eliminating residual green fluorescence present in DsRed. Finally, the mutant, called E57 (V105A, I161T, S197A), matures faster than DsRed as demonstrated in vitro with purified protein and in vivo with recombinant protein expressed in Escherichia coli and Xenopus leavis. Comparative analysis of the mutants in the context of the crystal structure of DsRed suggests that mutants with free space around the fluorophore mature faster and more completely. PMID- 11773063 TI - The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). AB - The substantial variations in the responses of cells to the anaphylatoxin C5a and its desarginated form, C5adR(74), suggest that more than one type of cell surface receptor for these ligands might exist. However, only a single receptor for C5a and C5adR(74), CD88, has been characterized to date. Here we report that the orphan receptor C5L2/gpr77, which shares 35% amino acid identity with CD88, binds C5a with high affinity but has a 10-fold higher affinity for C5adR(74) than CD88. C5L2 also has a moderate affinity for anaphylatoxin C3a, but cross-competition studies suggest that C3a binds to a distinct site from C5a. C4a was able to displace C3a, suggesting that C5L2, like the C3a receptor, may have a low binding affinity for this anaphylatoxin. Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca(2+)] and is not rapidly internalized in response to ligand binding. However, ligation of C5L2 by anaphylatoxin did potentiate the degranulation response to cross-linkage of the high affinity IgE receptor by a pertussis toxin-sensitive mechanism. These results suggest that C5L2 is an anaphylatoxin-binding protein with unique ligand binding and signaling properties. PMID- 11773064 TI - Repression of RNA polymerase I transcription by nucleolin is independent of the RNA sequence that is transcribed. AB - Nucleolin is one of the most abundant non-ribosomal proteins of the nucleolus. Several studies in vitro have shown that nucleolin is involved in several steps of ribosome biogenesis, including the regulation of rDNA transcription, rRNA processing, and ribosome assembly. However, the different steps of ribosome biogenesis are highly coordinated, and therefore it is not clear to what extent nucleolin is involved in each of these steps. It has been proposed that the interaction of nucleolin with the rDNA sequence and with nascent pre-rRNA leads to the blocking of RNA polymerase I (RNA pol I) transcription. To test this model and to get molecular insights into the role of nucleolin in RNA pol I transcription, we studied the function of nucleolin in Xenopus oocytes. We show that injection of a 2-4-fold excess of Xenopus or hamster nucleolin in stage VI Xenopus oocytes reduces the accumulation of 40 S pre-rRNA 3-fold, whereas transcription by RNA polymerase II and III is not affected. Direct analysis of rDNA transcription units by electron microscopy reveals that the number of polymerase complexes/rDNA unit is drastically reduced in the presence of increased amounts of nucleolin and corresponds to the level of reduction of 40 S pre-rRNA. Transcription from DNA templates containing various combinations of RNA polymerase I or II promoters in fusion with rDNA or CAT sequences was analyzed in the presence of elevated amounts of nucleolin. It was shown that nucleolin leads to transcription repression from a minimal polymerase I promoter, independently of the nature of the RNA sequence that is transcribed. Therefore, we propose that nucleolin affects RNA pol I transcription by acting directly on the transcription machinery or on the rDNA promoter sequences and not, as previously thought, through interaction with the nascent pre-rRNA. PMID- 11773065 TI - Activation of the p38 mitogen-activated protein kinase mediates the suppressive effects of type I interferons and transforming growth factor-beta on normal hematopoiesis. AB - Type I interferons (IFNs) are potent regulators of normal hematopoiesis in vitro and in vivo, but the mechanisms by which they suppress hematopoietic progenitor cell growth and differentiation are not known. In the present study we provide evidence that IFN alpha and IFN beta induce phosphorylation of the p38 mitogen activated protein (Map) kinase in CD34+-derived primitive human hematopoietic progenitors. Such type I IFN-inducible phosphorylation of p38 results in activation of the catalytic domain of the kinase and sequential activation of the MAPK-activated protein kinase-2 (MapKapK-2 kinase), indicating the existence of a signaling cascade, activated downstream of p38 in hematopoietic progenitors. Our data indicate that activation of this signaling cascade by the type I IFN receptor is essential for the generation of the suppressive effects of type I IFNs on normal hematopoiesis. This is shown by studies demonstrating that pharmacological inhibitors of p38 reverse the growth inhibitory effects of IFN alpha and IFN beta on myeloid (colony-forming granulocytic-macrophage) and erythroid (burst-forming unit-erythroid) progenitor colony formation. In a similar manner, transforming growth factor beta, which also exhibits inhibitory effects on normal hematopoiesis, activates p38 and MapKapK-2 in human hematopoietic progenitors, whereas pharmacological inhibitors of p38 reverse its suppressive activities on both myeloid and erythroid colony formation. In further studies, we demonstrate that the primary mechanism by which the p38 Map kinase pathway mediates hematopoietic suppression is regulation of cell cycle progression and is unrelated to induction of apoptosis. Altogether, these findings establish that the p38 Map kinase pathway is a common effector for type I IFN and transforming growth factor beta signaling in human hematopoietic progenitors and plays a critical role in the induction of the suppressive effects of these cytokines on normal hematopoiesis. PMID- 11773066 TI - AP-2 gamma and the homeodomain protein distal-less 3 are required for placental specific expression of the murine 3 beta-hydroxysteroid dehydrogenase VI gene, Hsd3b6. AB - The enzyme 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) is essential for the biosynthesis of all active steroid hormones. It exists as multiple isoforms in humans and rodents, each the product of a distinct gene. Human 3 beta-HSD I in placenta is essential for placental progesterone biosynthesis and thus is essential for the maintenance of pregnancy. The murine ortholog, 3 beta-HSD VI, is the only isoform expressed in giant trophoblast cells during the first half of mouse pregnancy. This study was designed to identify the cis-acting element(s) and the associated transcription factors required for trophoblast-specific expression of 3 beta-HSD VI. Transfection studies in placental and nonplacental cells identified a novel 66-bp trophoblast-specific enhancer element located between -2896 and -2831 of the 3 beta-HSD VI promoter. DNase protection analysis of the enhancer element identified three trophoblast specific binding sites, FPI, FPII, and FPIII. Electrophoretic mobility shift assays with oligonucleotides representing the protected sequences, FPI and FPIII, and nuclear extracts isolated from human JEG-3 cells and from mouse trophoblast cells, demonstrated the same binding pattern that was distinct from the binding pattern with mouse Leydig cell nuclear proteins. Further electrophoretic mobility shift assays identified AP-2 gamma and the homeodomain protein, Dlx 3, as the transcription factors that specifically bind to FPI and FPIII, respectively. Site specific mutations in each of the binding sites eliminated enhancer activity indicating that AP-2 gamma and Dlx 3, together with an additional transcription factor(s) that are conserved between humans and mice, are required for trophoblast-specific expression of 3 beta-HSD VI. PMID- 11773067 TI - Molecular mechanisms involved in CD43-mediated apoptosis of TF-1 cells. Roles of transcription Daxx expression, and adhesion molecules. AB - CD43 (leukosialin, sialophorin), an abundant leukocyte surface sialoglycoprotein, regulates leukocyte adhesion and transmits activating signals in T cells and dendritic cells. Immobilized anti-CD43 monoclonal antibody (mAb) MEM-59 has been previously shown to induce apoptosis of hematopoietic progenitors. In this study we show that it also triggers apoptosis of the myeloid progenitor-derived cell line TF-1. The kinetics of the MEM-59-induced apoptosis were unusually slow, with the first apoptotic cells appearing 36-48 h after their contact with the immobilized antibody; in 5 days, 90% of the cells were dead. CD43-mediated apoptosis was enhanced by coimmobilized anti-CD45 mAb and partly suppressed by coimmobilized anti-CD50 (ICAM-3) or anti-CD99 mAb. The MEM-59-triggered apoptosis of TF-1 cells was also inhibited by the overexpression of an apoptotic regulator, Daxx. CD43-mediated apoptosis was preceded by the repression of the DNA binding activity of the transcription factor AP-1. DNA array screening revealed that the expression of several genes encoding apoptosis-regulating proteins, including 14 3-3 proteins and the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor beta-subunit, was repressed in TF-1 cells bound to immobilized MEM-59. The down-regulation of 14-3-3 proteins and GM-CSF receptor beta was accompanied by translocation of the proapoptotic protein Bad to the mitochondria. These results suggest that engagement of CD43 may, presumably through the repressing transcription, initiate a Bad-dependent apoptotic pathway. PMID- 11773068 TI - Human biliverdin reductase is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress. AB - Human biliverdin reductase (hBVR) is a serine/threonine kinase that catalyzes reduction of the heme oxygenase (HO) activity product, biliverdin, to bilirubin. A domain of biliverdin reductase (BVR) has primary structural features that resemble leucine zipper proteins. A heptad repeat of five leucines (L(1)--L(5)), a basic domain, and a conserved alanine characterize the domain. In hBVR, a lysine replaces L(3). The secondary structure model of hBVR predicts an alpha helix-turn-beta-sheet for this domain. hBVR translated by the rabbit reticulocyte lysate system appears on a nondenaturing gel as a single band with molecular mass of approximately 69 kDa. The protein on a denaturing gel separates into two anti hBVR immunoreactive proteins of approximately 39.9 + 34.6 kDa. The dimeric form, but not purified hBVR, binds to a 100-mer DNA fragment corresponding to the mouse HO-1 (hsp32) promoter region encompassing two activator protein (AP-1) sites. The specificity of DNA binding is suggested by the following: (a) hBVR does not bind to the same DNA fragment with one or zero AP-1 sites; (b) a 56-bp random DNA with one AP-1 site does not form a complex with hBVR; (c) in vitro translated HO-1 does not interact with the 100-mer DNA fragment with two AP-1 sites; (d) mutation of Lys(143), Leu(150), or Leu(157) blocks both the formation of the approximately 69-kDa specimens and hBVR DNA complex formation; and (e) purified preparations of hBVR or hHO-1 do not bind to DNA with two AP-1 sites. The potential significance of the AP-1 binding is suggested by the finding that the response of HO-1, in COS cells stably transfected with antisense hBVR, with 66% reduced BVR activity, to superoxide anion (O(2)()) formed by menadione is attenuated, whereas induction by heme is not affected. We propose a role for BVR in the signaling cascade for AP-1 complex activation necessary for HO-1 oxidative stress response. PMID- 11773069 TI - Differential modulation of DNA conformation by estrogen receptors alpha and beta. AB - The human estrogen receptor (ER) induces transcription of estrogen-responsive genes upon binding to estrogen and the estrogen response element (ERE). To determine whether receptor-induced changes in DNA structure are related to transactivation, we compared the abilities of ER alpha and ER beta to activate transcription and induce distortion and bending in DNA. ER alpha induced higher levels of transcription than ER beta in the presence of 17 beta-estradiol. In circular permutation experiments ER alpha induced greater distortion in DNA fragments containing the consensus ERE sequence than ER beta. Phasing analysis indicated that ER alpha induced a bend directed toward the major groove of the DNA helix but that ER beta failed to induce a directed DNA bend. Likewise, the ER alpha DNA binding domain (DBD) and hinge region induced a bend directed toward the major groove of the DNA helix, but the ER beta DBD and hinge region failed to bend ERE-containing DNA fragments. Using receptor chimeras we demonstrated that the ER alpha DBD C-terminal extension is required for directed DNA bending. Transient transfection assays revealed that appropriately oriented DNA bending enhances receptor-mediated transactivation. The different abilities of ER alpha and ER beta to induce change in DNA structure could foster or inhibit the interaction of regulatory proteins with the receptor and other transcription factors and help to explain how estrogen-responsive genes are differentially regulated by these two receptors. PMID- 11773070 TI - DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. AB - DEF-1/ASAP1 is an ADP-ribosylation factor GTPase-activating protein (ARF GAP) that localizes to focal adhesions and is involved in cytoskeletal regulation. In this paper, we use a cell-based ARF GAP assay to demonstrate that DEF-1 functions as a GAP for ARF1 and not ARF6 in vivo. This degree of substrate preference was unique to DEF-1, as other ARF GAP proteins, ACAP1, ACAP2, and ARFGAP1, were able to function on both ARF1 and ARF6. Since transient overexpression of DEF-1 has been shown to interfere with focal adhesion formation and platelet-derived growth factor-induced membrane ruffling, we investigated whether NIH 3T3 cells stably expressing DEF-1 have altered cell motility. Here we report that ectopic DEF-1 enhances cell migration toward PDGF as well as IGF-1. This chemotactic effect appears to result from a general increase in cell motility, as DEF-1-expressing cells also exhibit enhanced levels of basal and chemokinetic motility. The increase in cell motility is dependent on DEF-1 GAP activity, since a DEF-1 mutant lacking the GAP domain failed to stimulate motility. This suggests that DEF-1 alters cell motility through the deactivation of ARF1. In contrast, the inhibition of cell spreading by DEF-1 was not dependent on GAP activity, indicating that spreading and motility are altered by DEF-1 through different pathways. PMID- 11773071 TI - Identification of residues required for the interaction of BARD1 with BRCA1. AB - The breast and ovarian cancer predisposition gene product BRCA1, binds to BARD1 at its N terminus. In cells BRCA1 is found as a heterodimer with BARD1 and may represent the functionally active form of BRCA1. Using yeast two-hybrid and split hybrid screens we have identified 16 independent missense mutations which prevent the ability of the BARD1 N terminus to heterodimerize with BRCA1. With reference to the recent structure of the BARD1center dotBRCA1 RING complex (Brzovic, P. S., Rajagopal, P., Hoyt, D. W., King, M-C., and Klevit, R. E. (2001) Nat. Struct. Biol. 8, 833--837) we note two classes of mutation; those that map to the hydrophobic core forming the BARD1:BRCA1 interface and are substitutions of leucine, and those that map to residues forming intramolecular contacts either in helical packing, or in the conserved zinc chelating cysteine residues of the RING itself. The directed mutation of charged residues predicted to play a role in the interaction could not alone prevent heterodimer formation suggesting that, while polar interactions may participate in the specificity of the interaction, they are not crucial. Together these data provide functional evidence for the requirement of a hydrophobic interface and illustrate that disruption of the tertiary structure by mutations away from the interface itself are able to prevent formation of the heterodimer. PMID- 11773072 TI - The carboxyl-terminal domain of closely related endotoxin-binding proteins determines the target of protein-lipopolysaccharide complexes. AB - The bactericidal/permeability increasing (BPI) and lipopolysaccharide (LPS) binding (LBP) proteins are closely related two-domain proteins in which LPS binding is mediated by the NH(2)-terminal domain. To further define the role of the COOH-terminal domain of these proteins in delivery of LPS to specific host acceptors, we have compared interactions of LBP, BPI, LBP(N)-BPI(C) (NH(2) terminal domain of LBP, COOH-terminal domain of BPI), and BPI(N)-LBP(C) with purified (3)H-LPS and, subsequently, with purified leukocytes and soluble (s)CD14. The COOH-terminal domain of LBP promotes delivery of LPS to CD14 on both polymorphonuclear leukocytes and monocytes resulting in cell activation. In the presence of Ca(2+) and Mg(2+), LBP and BPI each promote aggregation of LPS to protein-LPS aggregates of increased size (apparent M(r) > 20 x 10(6) Da), but only LPS associated with LBP and BPI(N)-LBP(C) is disaggregated in the presence of CD14. BPI and LBP(N)-BPI(C) promote apparently CD14-independent LPS association to monocytes without cell activation. These findings demonstrate that the carboxyl-terminal domain of these closely related endotoxin-binding proteins dictates the route and host responses to complexes they form with endotoxin. PMID- 11773073 TI - Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia. AB - The BAH genomic locus encodes three distinct proteins: junctin, humbug, and BAH. All three proteins share common exons, but differ significantly based upon the use of alternative terminal exons. The biological roles of BAH and humbug and their functional relationship to junctin remain unclear. To evaluate the role of BAH in vivo, the catalytic domain of BAH was specifically targeted such that the coding regions of junctin and humbug remained undisturbed. BAH null mice lack measurable BAH protein in several tissues, lack aspartyl beta-hydroxylase activity in liver preparations, and exhibit no hydroxylation of the epidermal growth factor (EGF) domain of clotting Factor X. In addition to reduced fertility in females, BAH null mice display several developmental defects including syndactyly, facial dysmorphology, and a mild defect in hard palate formation. The developmental defects present in BAH null mice are similar to defects observed in knock-outs and hypomorphs of the Notch ligand Serrate-2. In this work, beta hydroxylation of Asp residues in EGF domains is demonstrated for a soluble form of a Notch ligand, human Jagged-1. These results along with recent reports that another post-translational modification of EGF domains in Notch gene family members (glycosylation by Fringe) alters Notch pathway signaling, lends credence to the suggestion that aspartyl beta-hydroxylation may represent another post translational modification of EGF domains that can modulate Notch pathway signaling. Previous work has demonstrated increased levels of BAH in certain tumor tissues and a role for BAH in tumorigenesis has been proposed. The role of hydroxylase in tumor formation was tested directly by crossing BAH KO mice with an intestinal tumor model, APCmin mice. Surprisingly, BAH null/APCmin mice show a statistically significant increase in both intestinal polyp size and number when compared with BAH wild-type/APCmin controls. These results suggest that, in contrast to expectations, loss of BAH catalytic activity may promote tumor formation. PMID- 11773075 TI - The chloroplast protein import receptors Toc34 and Toc159 are phosphorylated by distinct protein kinases. AB - The molecular composition of chloroplast outer and inner envelope translocons is fairly well established, but little is known about mechanisms and elements involved in import regulation. After synthesis in the cytosol, chloroplast targeted precursor proteins are recognized by outer envelope receptors Toc34 and Toc159. Phosphorylation plays an important role in regulation of Toc34 activity and preprotein binding. Using kinase renaturation assays, we have identified an ATP-dependent 98-kDa outer envelope kinase which is able to selectively phosphorylate Toc34 at a specific site. A 70-kDa outer envelope polypeptide phosphorylating Toc159 was identified by the same strategy. Antiserum against the 98-kDa kinase inhibits phosphorylation of Toc34, whereas labeling of Toc159 remains unaffected. Both kinases do not autophosphorylate in vitro and are unable to utilize myelin basic protein as substrate. We propose that distinct kinases are involved in regulation of chloroplast import via desensitization of preprotein receptors. PMID- 11773074 TI - A human RNA polymerase II-containing complex associated with factors necessary for spliceosome assembly. AB - Transcription and splicing are coordinated processes in mammalian cells. We have used affinity chromatography with immobilized transcription elongation factor SII to purify a protein complex that contains core RNA polymerase II (RNA Pol II), the general transcription initiation factors, and several splicing factors, including the U1, U2, and U4 small nuclear RNPs, the U2AF(65), and serine/arginine-rich proteins. The splicing factors and the transcription machinery co-purify through a gel filtration column and co-immunoprecipitate in experiments using an anti-U2AF(65) antibody, indicating that they are part of a unique complex. Although the RNA Pol II-containing complex does not possess splicing activity, it can complement small nuclear RNP-inactivated extracts and can promote the formation of a pre-spliceosome complex. Because interactions between components of the splicing and transcription machineries occur in the context of a complex containing a hypophosphorylated RNA Pol II capable of initiating transcription, our results suggest that the coupling between transcription and splicing begins before transcription initiation. PMID- 11773076 TI - The hemopexin-like C-terminal domain of membrane type 1 matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR. AB - Matrix metalloproteinases (MMPs) including membrane type 1 MMP (MT1-MMP) can degrade extracellular matrix and cell surface receptor molecules and have an essential function in malignancy. Recently, we established a functional link between MT1-MMP and the receptor of complement component 1q (gC1qR). The gC1qR is known as a compartment-specific regulator of diverse cellular and viral proteins. Once released by proliferating cells, soluble gC1qR may inhibit complement component 1q hemolytic activity and play important roles in vivo in assisting tumor cells to evade destruction by complement. Here, we report that gC1qR is susceptible to MT1-MMP proteolysis in vitro and in cell cultures. The major MT1 MMP cleavage site (Gly(79) down arrow Gln(80)) is localized within the structurally disordered loop connecting the beta(3) and the beta(4) strands of gC1qR. The recombinant MT1-MMP construct that included the catalytic domain but lacked the hemopexin-like domain lost the proteolytic capacity; however, it retained the ability to bind gC1qR. Inhibition of MT1-MMP activity by a hydroxamate inhibitor converted the protease into a cell surface receptor of gC1qR and promoted co-precipitation MT1-MMP with the soluble gC1qR protein. It is tempting to hypothesize that these novel mechanisms may play important roles in vivo and have to be taken into account in designing hydroxamate-based cancer therapy. PMID- 11773077 TI - Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation. AB - Previous studies have shown that the transcriptional coactivator protein Gcn5 functions as a catalytic histone acetyltransferase (HAT). In this work, we examine the roles of the Ada2 and Ada3 coactivator proteins that are functionally linked to Gcn5. We show that yeast Ada2, Ada3, and Gcn5 form a catalytic core of the ADA and Spt-Ada-Gcn5-acetyltransferase HAT complexes, which is necessary and sufficient in vitro for nucleosomal HAT activity and lysine specificity of the intact HAT complexes. We also demonstrate that Ada3 is necessary for Gcn5 dependent nucleosomal HAT activity in yeast extracts. Our results suggest that Ada2 potentiates the Gcn5 catalytic activity and that Ada3 facilitates nucleosomal acetylation and an expanded lysine specificity. PMID- 11773078 TI - Kinetic analysis of the interaction between vitronectin and the urokinase receptor. AB - Although the urokinase receptor (uPAR) binds to vitronectin (VN) and promotes the adhesion of cells to this matrix protein, the biochemical details of this interaction remain unclear. VN variants were employed in BIAcore experiments to examine the uPAR-VN interaction in detail and to compare it to the interaction of VN with other ligands. Heparin and plasminogen bound to VN fragments containing the heparin-binding domain, indicating that this domain was functionally active in the recombinant peptides. However, no significant binding was detected when uPAR was incubated with this domain, and neither heparin nor plasminogen competed with it for binding to VN. In fact, uPAR only bound to fragments containing the somatomedin B (SMB) domain, and monoclonal antibodies (mAbs) that bind to this domain competed with uPAR for binding to VN. Monoclonal antibody 8E6 also inhibited uPAR binding to VN, and this mAb was shown to recognize sulfated tyrosine residues 56 and 59 in the region adjacent to the SMB domain. Destruction of this site by acid treatment eliminated mAb 8E6 binding but had no effect on uPAR binding. Thus, there appears to be a single binding site for uPAR in VN, and it is located in the SMB domain and is distinct from the epitope recognized by mAb 8E6. Inhibition of uPAR binding to VN by mAb 8E6 probably results from steric hindrance. PMID- 11773079 TI - Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a. AB - Signal transducer and activator of transcription 3 (STAT3) transcription factors are cytoplasmic proteins that induce gene activation in response to cytokine receptor stimulation. Following tyrosine phosphorylation, STAT3 proteins dimerize, translocate to the nucleus, and activate specific target genes. This transcriptional activation by STAT3 proteins has been shown to require the recruitment of coactivators such as CREB-binding protein (CBP)/p300. In the present study, we show that steroid receptor coactivator 1, NcoA/SRC1a, originally identified as a nuclear receptor coactivator, also functions as a coactivator of STAT3 proteins. In coimmunoprecipitations, NcoA/SRC1a was found to associate with STAT3 following IL-6 stimulation of HepG2 hepatoma cells. Pull down experiments indicated that the N-terminal part of NcoA/SRC1a associates with the activation domain of STAT3. Overexpression of NcoA/SRC1a or its SRC1e isoform enhanced transcriptional activation by STAT3 proteins in transient transfection experiments. This ability of NcoA/SRC1a to enhance STAT3 activity is dependent upon the presence of the CBP-interacting domain, activation domain 1. Using chromatin immunoprecipitation assays, we found that STAT3, NcoA/SRC1a, and CBP/p300 are simultaneously recruited to the p21(waf1) promoter following interleukin-6 stimulation. Taken together, these data suggest that CBP/p300 and NcoA/SRC1a may function in a common pathway to regulate STAT3 transcriptional activity. PMID- 11773080 TI - Distinct residues in the carboxyl tail mediate agonist-induced desensitization and internalization of the human dopamine D1 receptor. AB - We have shown in a previous study that desensitization and internalization of the human dopamine D(1) receptor following short-term agonist exposure are mediated by temporally and biochemically distinct mechanisms. In the present study, we have used site-directed mutagenesis to remove potential phosphorylation sites in the third intracellular loop and carboxyl tail of the dopamine D(1) receptor to study these processes. Mutant D(1) receptors were stably transfected into Chinese hamster ovary cells, and kinetic parameters were measured. Mutations of Ser/Thr residues to alanine in the carboxyl tail demonstrated that the single substitution of Thr-360 abolished agonist-induced phosphorylation and desensitization of the receptor. Isolated mutation of the adjacent glutamic acid Glu-359 also abolished agonist-induced phosphorylation and desensitization of the receptor. These data suggest that Thr-360 in conjunction with Glu-359 may comprise a motif necessary for GRK2-mediated phosphorylation and desensitization. Agonist-induced internalization was not affected with mutation of either the Thr 360 or the Glu-359 residues. However, receptors with Ser/Thr residues mutated in the distal carboxyl tail (Thr-446, Thr-439, and Ser-431) failed to internalize in response to agonist activation, but were able to desensitize normally. These results indicate that agonist-induced desensitization and internalization are regulated by separate and distinct serine and threonine residues within the carboxyl tail of the human dopamine D(1) receptor. PMID- 11773081 TI - The retinoblastoma family of proteins directly represses transcription in Saccharomyces cerevisiae. AB - The retinoblastoma family of proteins are key cell cycle regulatory molecules important for the differentiation of various mammalian cell types. The retinoblastoma protein regulates transcription of a variety of genes either by blocking the activation domain of various activators or by active repression via recruitment to appropriate promoters. We show here that the retinoblastoma family of proteins functions as direct transcriptional repressors in a heterologous yeast system when fused to the DNA binding domain of Gal4. Mapping experiments indicate that either the A or the B domain of the pocket region is sufficient for repression in vivo. As is the case in mammalian cells, a phosphorylation site mutant of the retinoblastoma protein is a stronger transcriptional repressor than the wild type protein. We show that transcriptional repression by pRb is dependent on CLN3 in vivo. Furthermore, the yeast histone deacetylase components, RPD3 and SIN3, are required for transcriptional repression. PMID- 11773082 TI - The Slp homology domain of synaptotagmin-like proteins 1-4 and Slac2 functions as a novel Rab27A binding domain. AB - rab27A, which encodes a small GTP-binding protein, was recently identified as a gene in which mutations caused human hemophagocytic syndrome (Griscelli syndrome) and ashen mice, which exhibit defects in melanosome transport as well as in regulated granule exocytosis in cytotoxic T lymphocytes. However, little is known about the molecular mechanism of Rab27A-dependent membrane trafficking or the specific effector molecules of Rab27A. In this study, we discovered that the Slp (synaptotagmin-like protein) homology domain (SHD) of Slp1--3 and Slac2-a/b specifically and directly binds the GTP-bound form of Rab27A both in vitro and in intact cells but not of the other Rabs tested (Rab1, Rab2, Rab3A, Rab4, Rab5A, Rab6A, Rab7, Rab8, Rab9, Rab10, Rab11A, Rab17, Rab18, Rab20, Rab22, Rab23, Rab25, Rab28, and Rab37). Immunocytochemical analysis revealed that Slp2 (or Slp1) colocalized with Rab27A in the melanosomes of melanoma cells. Slp2 and Rab27A were distributed to the periphery of the cells (especially at the dendritic tips) in the wild-type melanoma cells, whereas they accumulated in the perinuclear region in the melanosome transport-defective cells (S91/Cloudman). These results strongly indicated that the SHD of Slp1--3 and Slac2 functions as an in vivo Rab27A binding domain. PMID- 11773083 TI - Hunting health care-associated infections from the clinical microbiology laboratory: passive, active, and virtual surveillance. PMID- 11773084 TI - Detection of measles virus-specific immunoglobulin M in dried venous blood samples by using a commercial enzyme immunoassay. AB - The optical densities (ODs) of 216 dried venous blood (DVB) samples submitted to the Victorian Infectious Diseases Reference Laboratory as part of enhanced measles surveillance were compared to the ODs of the corresponding serum samples collected at the same time. DVB samples, stored for up to 24 months at 4 degrees C, were tested by the Dade Behring Enzygnost Anti-Measles-Virus/IgM immunoassay. Elution and testing conditions were optimized with the use of spiked DVB samples. The assay showed an overall sensitivity of 90.2% and a specificity of 98.8% for DVB samples compared to the results for serum. When the results were analyzed according to the length of time that the DVB sample had been stored, the assay was 100% sensitive and 97% specific according to the ODs for those samples stored for less than 6 months compared to the results for the corresponding serum samples, with 97.7% agreement between the results for the two sample types. These results demonstrate the potential for the use of DVB samples for the diagnosis of measles in routine diagnostic laboratories. PMID- 11773085 TI - Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. AB - Two outbreaks of hand-foot-and-mouth disease (HFMD) occurred in Taiwan between 1998 and 2000. Enteroviruses were isolated from a total of 1,892 patients in this laboratory during this period. Of the virus isolates, enterovirus 71 (EV71) was diagnosed in 44.4% of the patients (132 of 297) in 1998, 2% (13 of 646) in 1999, and 20.5% (195 of 949) in 2000. Genetic analyses of the 5'-untranslated and VP1 regions of EV71 isolates by reverse transcription-PCR and sequencing were performed to understand the diversity of EV71 in these outbreaks of HFMD. Most EV71 isolates from the 1998 epidemic belonged to genotype C, while only one-tenth of the isolates were genotype B. Interestingly, all EV71 isolates tested from 1999 to 2000 belonged to genotype B. This study indicated that two genogroups of EV71 capable of inducing severe clinical illness have been circulating in Taiwan. Furthermore, the predominant EV71 genotypes responsible for each of the two major HFMD outbreaks within the 3-year period in Taiwan were different. PMID- 11773087 TI - Clinical and virological aspects of blood donors infected with hepatitis B virus genotypes B and C. AB - Pathogenic and therapeutic differences among hepatitis B virus (HBV) genotypes have been documented. However, the association of virological characteristics with clinical differences among HBV genotypes remains unclear. We therefore studied the clinical and virological characteristics of Taiwanese volunteer blood donors infected with HBV genotypes B and C. HBV genotypes were determined in 300 candidate blood donors positive for HBV surface antigen (HBsAg), and sequences of the precore gene of the HBV genome were determined in 50 HBV e antigen (HBeAg) positive and 50 HBeAg-negative blood donors. Of 300 HBsAg-positive blood donors, 10% had elevated serum aminotransferase levels and 27% were positive for HBeAg. HBV genotype distribution in 264 viremic carriers was as follows: B, 221 (83.7%); C, 39 (14.8%); F, 1 (0.4%); and mixed infection, 3 (1.1%). Blood donors with genotype C infection tended to have a higher frequency of HBeAg positivity and a higher serum HBV DNA level than those with genotype B infection. The frequency of precore stop codon mutation was significantly higher in HBeAg-negative blood donors than HBeAg-positive ones, irrespective of HBV genotypes. Meanwhile, only 5% of blood donors with genotype C infection had C-1858 strains. In conclusion, mixed infection of HBV genotypes indeed occurs, and genotype C has a higher serum HBV DNA level than genotype B. Precore stop codon mutation is common in HBeAg negative HBV carriers, irrespective of HBV genotypes. In contrast, precore C-1858 strains are rarely identified in Taiwanese HBV genotype C. PMID- 11773086 TI - Precore stop mutant in HBeAg-positive patients with chronic hepatitis B: clinical characteristics and correlation with the course of HBeAg-to-anti-HBe seroconversion. AB - This study aimed to investigate the ratios of precore stop mutant (codon 28; TGG to TAG) to total viremia in 53 HBeAg-positive patients with chronic hepatitis B by amplification-created restriction site assays along the course of HBeAg-to anti-HBe seroconversion. At baseline, 11% had exclusive wild-type hepatitis B virus (HBV), 15% had exclusively precore mutant, and 74% had mixed viral strains. Precore mutant ratios correlated little with age, sex, or HBV DNA levels (all P > 0.1), but correlated modestly with alanine aminotransferase (ALT) levels (P = 0.05). The intervals from presentation to anti-HBe seroconversion correlated significantly with ALT and precore mutant ratios in univariate analysis but with only precore mutant ratios in multivariate analysis (P = 0.003). Precore mutant ratios at baseline were significantly higher (P < 0.001) in six patients with persistent high viremia and ALT elevation after anti-HBe seroconversion (group 1) than in 47 with remission (group 2). All group 1 patients had exclusive precore mutant after anti-HBe seroconversion, as did only 14 (30%) of the group 2 patients (P = 0.003). Among group 2 patients, precore mutant ratios at baseline or after anti-HBe seroconversion showed no significant difference between 34 patients with sustained remission and 13 with relapse. Cirrhosis developed in 50% (5 of 10) of patients with precore mutant ratios >50% at baseline but only in 12% (5 of 43) of those with precore mutant ratios of <50% at baseline (P < 0.05). In conclusion, precore mutant of variable ratios was frequently detected in HBeAg positive patients with chronic hepatitis B. Precore mutant ratios tended to correlate with ALT levels and anti-HBe seroconversion, but high precore mutant ratios were associated with persistent hepatitis after anti-HBe seroconversion and increased risk of cirrhosis. PMID- 11773088 TI - Comparison of two culture methods for detection of tobramycin-resistant gram negative organisms in the sputum of patients with cystic fibrosis. AB - A culture method utilizing quantitative plating on antibiotic-containing media has been proposed as a technique for the detection of tobramycin-resistant organisms that is more sensitive than standard methods. Typical sputum culture methods quantitate the relative amounts of each distinct morphotype, followed by antibiotic susceptibility testing of a single colony of each morphotype. Sputum specimens from 240 cystic fibrosis patients were homogenized, serially diluted, and processed in parallel by the standard method (MacConkey agar and OF basal medium with agar, polymyxin, bacitracin, and lactose) and by plating on antibiotic-containing media (MacConkey agar with tobramycin added at 25 microg/ml [MAC-25] and 100 microg/ml [MAC-100]). MICs of tobramycin were determined for all Pseudomonas aeruginosa isolates by broth microdilution. Growth of P. aeruginosa on MAC-25 was considered to be equivalent to a tobramycin MIC of > or = 16 microg/ml, and growth on MAC-100 was considered to be equivalent to a tobramycin MIC of > or = 128 microg/ml. Analysis of method-specific detection rates showed that tobramycin-containing medium was more sensitive than the standard method for the detection of tobramycin-resistant P. aeruginosa, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans but was less sensitive for the detection of Burkholderia cepacia than the standard method. When MICs for P. aeruginosa that grew on tobramycin-containing medium were tested by broth microdilution, the MICs for 28 of 121 strains (23%) growing on MAC-25 and 22 of 56 strains (39%) growing on MAC-100 were MICs < 16 and < 128 microg/ml, respectively. Addition of a tobramycin-containing MacConkey plate to the routine media for sputum culture may provide additional, clinically relevant microbiologic data. PMID- 11773089 TI - Comparative analysis of two commercial phenotypic assays for drug susceptibility testing of human immunodeficiency virus type 1. AB - Human immunodeficiency virus type 1 (HIV-1) isolates from 50 plasma specimens were analyzed for phenotypic susceptibility to licensed reverse transcriptase inhibitors and protease inhibitors by the Antivirogram and PhenoSense HIV assays. Twenty of these specimens were from recently seroconverted drug-naive persons, and 30 were from patients who were the sources of occupational exposures to HIV 1; 16 of the specimens in the latter group were from drug-experienced patients. The phenotypic results of the Antivirogram and PhenoSense HIV assays were categorized as sensitive or reduced susceptibility on the basis of the cutoff values established by the manufacturers of each assay. Data for 12 to 15 drugs were available by both assays for 38 specimens and represented a total of 529 pairs of results. The two data sets had a 91.5% concordance by phenotypic category. The discordant results (n = 45) were distributed randomly among 26 specimens and included 28 results (62.2%) which were within a twofold difference of the assay cutoff values. None of the discordant results were associated with primary resistance mutations that predicted high-level (>20-fold) resistance. Discordant results were distributed equally among specimens from drug-experienced and drug-naive individuals and were slightly higher for protease inhibitors than for nonnucleoside reverse transcriptase inhibitors or nucleoside reverse transcriptase inhibitors. The findings of the present study demonstrate that the results of the Antivirogram and PhenoSense HIV assays correlate well, despite the use of different testing strategies. PMID- 11773090 TI - Distribution of clinically relevant Borrelia genospecies in ticks assessed by a novel, single-run, real-time PCR. AB - A LightCycler-based PCR protocol was developed which targets the ospA gene for the identification and quantification of the different Borrelia burgdorferi sensu lato species in culture and in ticks, based on the use of a fluorescently labeled probe (HybProbe) and an internally labeled primer. The detection limit of the PCR was 1 to 10 spirochetes. A melting temperature determined from the melting curve of the amplified product immediately after thermal cycling allowed the differentiation of the three different B. burgdorferi sensu lato genospecies (B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii) that are clinically relevant in Europe in a single PCR run. This method represents a simplified approach to study the association of different Borrelia species in ticks, the risk of Lyme borreliosis, and the putatively species-specific clinical sequelae. To determine the reliability of the real-time PCR protocol, we studied the prevalence of B. burgdorferi sensu lato infection in Ixodes ricinus ticks. A total of 1,055 ticks were collected by flagging vegetation in five different sites in the region of Konstanz (south Germany) and were examined for the distribution of B. burgdorferi species by real-time PCR. The mean infection rate was 35%. Of 548 adult ticks, 40% were positive, and of 507 nymphs, 30% were positive. The predominant genospecies (with 18% mixed infections) in the examined areas was B. afzelii (53%), followed by B. garinii (18%) and B. burgdorferi sensu stricto (11%); 0.8% of the infecting Borrelia could not be identified. PMID- 11773091 TI - Immune reactivity of human sera to the glycoprotein B of human herpesvirus 7. AB - The glycoprotein B (gB) is highly conserved among distinct human herpesvirus 7 (HHV-7) strains. Similarly to other herpesvirus glycoproteins, gB has been assumed to induce a specific human immune response. However, it did not appear as an immunodominant protein in conventional immunoblot assays. Recombinant gB, obtained from either Escherichia coli or baculovirus expression systems, did react specifically with HHV-7-seropositive sera, and the main corresponding epitopes were located in its N-terminal part. A 24-amino-acid peptide, corresponding to a predicted hydrophilicity peak and presenting no extensive homology with other betaherpesvirus glycoproteins, was selected in this region at positions 129 to 152 of the gB sequence. When tested by enzyme-linked immunosorbent assay (ELISA), this peptide specifically reacted with HHV-7 seropositive sera. This reactivity was significantly inhibited by the preincubation of sera with the peptide itself, lysates of gB-expressing cells, or lysates of HHV-7-infected cells. The reactivity was not significantly modified when sera were preincubated with lysates of either human cytomegalovirus (HCMV)- or HHV-6-infected cells. In cross-sectional studies including both children and adults, 49 out of 61 serum samples (80%) were found to be positive by HHV-7 ELISA, independent of their reactivity to HCMV. A longitudinal serological study of 17 children during the first 4 years of life showed that the level of ELISA detected antibodies significantly decreased within a few weeks after birth and then increased in the following months, likely reflecting, respectively, the loss of maternal antibodies and the occurrence of seroconversion. These results demonstrate that gB peptide ELISA might be a useful tool for the serological study of HHV-7 infection. PMID- 11773092 TI - Modeling of 5' nuclease real-time responses for optimization of a high-throughput enrichment PCR procedure for Salmonella enterica. AB - The performance of a 5' nuclease real-time PCR assay was studied to optimize an automated method of detection of preenriched Salmonella enterica cells in buffered peptone water (BPW). The concentrations and interactions of the PCR reagents were evaluated on the basis of two detection responses, the threshold cycle (C(T)) and the fluorescence intensity by a normalized reporter value (DeltaR(n)). The C(T) response was identified as the most suitable for detection modeling to describe the PCR performances of different samples. DNA extracted from S. enterica serovar Enteritidis was studied in double-distilled H2O (ddH2O) and in two different enrichment media (brain heart infusion and BPW) with two PCR mixtures based on AmpliTaq Gold or rTTH: A descriptive model was proposed and fitted to the available experimental data. Equivalent PCR performances for the two PCR mixtures were obtained when DNA was diluted in ddH2O. However, the level of detection of DNA was affected when BPW was present during amplification. Use of the rTth mixture generated a 1-log-unit wider linear range of amplification, and the DNA detection levels were 2 x 10(-13) g/microwell for the rTth mixture and 2 x 10(-12) g/microwell for the AmpliTaq Gold mixture. To verify the improved amplification capacity of the rTth mixture, BPW was inoculated with 1 CFU of S. enterica serovar Enteritidis per ml and the mixture was incubated at 30 degrees C. Samples for PCR were withdrawn every 4 h during a 36-h enrichment. Use of the rTth mixture resulted in an earlier PCR detection during enrichment than use of the AmpliTaq Gold mixture. For accurate detection (C(T) < or = 30) of S. enterica serovar Enteritidis inoculated in BPW, the rTth mixture required 8.4 h of enrichment, while the AmpliTaq Gold mixture needed 11.6 h. In conclusion, the principle applied can improve the methodology of 5' nuclease real-time PCR for numerical optimization of sample pretreatment strategies to provide automated diagnostic PCR procedures. PMID- 11773093 TI - Antigenic heterogeneity of the hepatitis C virus NS5A protein. AB - The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenic properties of the NS5 protein was studied by using recombinant proteins. A strong antigenic region was identified within the HCV NS5A protein at amino acids 2212 to 2313. Forty-five unique sequences encompassing this region were selected from GenBank and were compared to each other. The results of this analysis showed that the primary structure of this strong antigenic region is highly variable. Percent homology between different genotype sequences varied from 40.4 to 72.5%. Thirteen representative sequences from all six HCV genotypes were selected to design synthetic genes coding for this antigenic region. These genes were assembled by PCR from synthetic oligonucleotides and expressed in Escherichia coli as hybrid proteins with glutathione S-transferase. All 13 fusion proteins were purified from bacterial lysates and used to test a panel of anti-HCV positive sera (n = 91) obtained from patients infected with HCV genotypes 1 through 6. All but two proteins immunoreacted with 62 to 93% of HCV anti-NS5-positive serum samples. Although a variable degree of genotype-specific antigenic reactivity was detected, only one protein demonstrated a noticeable preference to immunoreact with antibodies against the homologous HCV genotype. On the other hand, closely related proteins derived from the same subtype or genotype immunoreacted with significantly different efficiency with HCV antibodies. Thus, sequence variability has a profound effect on the antigenic properties of the NS5A immunodominant regions. This observation should be taken into consideration in the development of diagnostic tests for the efficient detection of anti-HCV activity in serum specimens. PMID- 11773094 TI - Emergence of penicillin-nonsusceptible Streptococcus pneumoniae invasive clones in Canada. AB - Distinctive international clones of penicillin-nonsusceptible and multidrug resistant Streptococcus pneumoniae are increasingly being reported. We investigated the spread of these clones in Canada through an active surveillance that was carried out at 11 Canadian pediatric tertiary care centers from 1991 to 1998. All penicillin-nonsusceptible isolates were serotyped, tested for antibiotic susceptibility, and genotyped by pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD). Forty-five penicillin nonsusceptible S. pneumoniae isolates were evaluated. Eleven serotype 9V isolates and six serotype 14 isolates displayed identical RAPD and PFGE fingerprint profiles. Twelve (70%) of these isolates were encountered in Quebec. The 9V/14 clone and the Spanish-French clone had similar PFGE fingerprint patterns. Eight isolates of serotype 23F and two isolates of serogroup 14 had the same fingerprint profiles and displayed resistance to three or more antibiotic drug classes. This clone was first detected in Calgary (Alberta) and in 1996 appeared simultaneously in various regions of Canada. This clone showed a PFGE fingerprint pattern similar to that of the Spanish-U.S. 23F clone. Our data show the emergence across Canada of two international clones of penicillin-nonsusceptible S. pneumoniae: (i) serotypes 9V and 14 related to the Spanish-French clone and (ii) the 23F Spanish-U.S. clone. The source of the first clone was in Quebec and the second international clone was probably originated from the United States. The exact reasons for the successful spread of these clones within Canada and their contribution to increased resistance to antibiotics have yet to be explored. PMID- 11773095 TI - Detection of meningococcal carriage by culture and PCR of throat swabs and mouth gargles. AB - The standard method for detecting meningococcal carriage is culture of throat swabs on selective media, but the levels of carriage determined depend heavily on the skills of the individuals taking the swab and interpreting the cultures. This study aimed to determine the most sensitive detection method for meningococcal carriage. Throat swabs and saline mouth gargles, obtained from 89 university students, were processed in parallel by conventional culture and TaqMan ctrA PCR. Carriage of meningococci, as detected by the combined methods, was 20%. The sensitivities of throat swab culture, throat swab PCR, gargle culture, and gargle PCR were 72, 56, 56, and 50%, respectively, and the probabilities that these techniques would correctly identify the absence of carriage (negative predictive value [NPV]) were 93.4, 89.9, 89.9, and 88.8%. Culturing both throat swabs and gargles increased the NPV to 98.6%. The further addition of throat swab PCR increased this to 100%. Testing gargles by both culture and PCR was as sensitive as testing throat swabs by both methods, suggesting that gargles may be a suitable alternative for large-scale screening studies when throat swabs are difficult to obtain, although they required more lengthy laboratory processing. PCR was a useful adjunct to culture for detecting nasopharyngeal carriage, but it failed to detect some nongroupable strains. For maximum sensitivity, a combination of techniques was required. This study indicates the confidence with which health care professionals involved in meningococcal screening can regard laboratory results. PMID- 11773096 TI - Immunochromatographic strip test for rapid detection of diphtheria toxin: description and multicenter evaluation in areas of low and high prevalence of diphtheria. AB - An immunochromatographic strip (ICS) test was developed for the detection of diphtheria toxin by using an equine polyclonal antibody as the capture antibody and colloidal gold-labeled monoclonal antibodies specific for fragment A of the diphtheria toxin molecule as the detection antibody. The ICS test has been fully optimized for the detection of toxin from bacterial cultures; the limit of detection was approximately 0.5 ng of diphtheria toxin per ml within 10 min. In a comparative study with 915 pure clinical isolates of Corynebacterium spp., the results of the ICS test were in complete agreement with those of the conventional Elek test. The ICS test was also evaluated for its ability to detect toxigenicity from clinical specimens (throat swabs) in two field studies conducted within areas of the former USSR where diphtheria is epidemic. Eight hundred fifty throat swabs were examined by conventional culture and by use of directly inoculated broth cultures for the ICS test. The results showed 99% concordance (848 of 850 specimens), and the sensitivity and specificity of the ICS test were 98% (95% confidence interval, 91 to 99%) and 99% (95% confidence interval, 99 to 100%), respectively. PMID- 11773097 TI - Detection of amantadine-resistant influenza A virus strains in nursing homes by PCR-restriction fragment length polymorphism analysis with nasopharyngeal swabs. AB - Annual consumption of amantadine increased abruptly after its approval for the treatment of influenza A virus infections in Japan in 1998, and the emergence of amantadine-resistant viruses is now a matter of concern. To detect resistant influenza A virus strains, we have developed a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for nasopharyngeal swabs. Three different primer sets for nested PCR were designed to incorporate restriction sites into the amplicon to differentiate single-amino-acid substitutions at positions 27, 30, and 31 that confer resistance in the transmembrane domain of the M2 protein. Each PCR product was digested with respective endonucleases (BspLU11I for amino acid change at position 27, HhaI for position 30, and ScaI for position 31), and the polymorphisms were determined by electrophoresis. Thirty-four (24.1%) of 141 PCR positive samples had resistance patterns in eight nursing homes in the 1998-1999 season. Thirty-one viruses (91.2%) showed a change at position 31 (serine to asparagine), three viruses (8.8%) showed a change at position 30 (alanine to threonine), and none showed a change at position 27. The incidence of resistant viruses did not show any significant difference between four facilities where amantadine was used mainly for influenza treatment and four other facilities where it was used only for Parkinson's disease, values being 27.6 and 16.3%, respectively. We have confirmed that the PCR-RFLP method is useful for detecting amantadine-resistant strains directly from nasopharyngeal swabs and that resistant viruses were circulating in nursing homes where the drug was used not only for influenza virus but also for Parkinson's disease. PMID- 11773098 TI - Development and validation of a PCR-based enzyme-linked immunosorbent assay with urine for use in clinical research settings to detect Trichomonas vaginalis in women. AB - Trichomonas vaginalis infection is highly prevalent worldwide and is associated with poor birth outcomes and enhanced human immunodeficiency virus transmission. Traditional detection methods rely on microscopic examination of vaginal specimens (wet mount) and culture, which can be insensitive and time-consuming. More than 3,000 women attending two sexually transmitted disease clinics were enrolled in this cross-sectional study to evaluate urine-based PCR for detection of T. vaginalis using a combined reference standard of wet mount and culture from vaginal swab. The prevalence of trichomoniasis in the population was 16.7% (502 of 3,009 women) using the reference standard. PCR with urine combined with agarose gel-based detection was 66.9% sensitive and 98.3% specific compared to the reference standard. Detection of PCR products using an unlabeled enzyme linked immunosorbent assay (ELISA) improved the sensitivity to 86.4%, but specificity fell to 86.1%. Using a digoxigenin-labeled ELISA for detection of amplified T. vaginalis DNA from urine, the sensitivity and specificity of the PCR improved to 90.8 and 93.4%, respectively, compared to wet mount or culture from vaginal swabs. For clinical research settings in which vaginal specimens are not available and culture conditions are not feasible, urine-based PCR-ELISA may be useful for the detection of trichomoniasis in women. PMID- 11773099 TI - Multiplex LightCycler PCR assay for detection and differentiation of Bordetella pertussis and Bordetella parapertussis in nasopharyngeal specimens. AB - A rapid real-time multiplex PCR assay for detecting and differentiating Bordetella pertussis and Bordetella parapertussis in nasopharyngeal swabs was developed. This assay (LC-PCR-IS) targets the insertion sequences IS481 and IS1001 of B. pertussis and B. parapertussis, respectively, and is performed using the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.). The analytical sensitivity is less than one organism per reaction. Results for Bordetella culture and/or direct fluorescent antibody testing and a second LightCycler PCR assay (target, pertussis toxin gene) were compared to results of the LC-PCR-IS assay for 111 nasopharyngeal swabs submitted for pertussis testing. Of the specimens, 12 were positive (9 B. pertussis and 3 B. parapertussis) and 68 specimens were negative by all methods. Three other specimens were positive for B. pertussis by at least two of the methods (including the LC-PCR-IS assay), and another 28 specimens were positive for B. pertussis by the LC-PCR-IS assay only. No specimens were negative by the LC-PCR-IS assay and positive by the other methods. A conventional PCR method (target, IS481) was also compared to the LC PCR-IS assay for a different group of nasopharyngeal swab specimens (n = 96): 44 specimens were positive and 41 specimens were negative for B. pertussis with both PCR methods. Nine specimens were positive for B. pertussis by the LC-PCR-IS assay and negative by the conventional PCR assay, and two specimens were positive for B. pertussis by the conventional PCR assay and negative by the LC-PCR-IS assay. Positivity of the two assays was not significantly different (P = 0.0654). The insertion sequence IS481 is also present in Bordetella holmesii; specimens containing B. holmesii may yield false-positive results. The LC-PCR-IS assay takes approximately 45 min to complete post-nucleic acid extraction, compared to 24 h for the conventional PCR assay previously used in our laboratory. The LC-PCR IS assay is easier to perform than the conventional PCR assay, and the closed system decreases the chance of contamination. All of these characteristics represent a significant improvement in the detection of B. pertussis and B. parapertussis in nasopharyngeal specimens. PMID- 11773100 TI - Molecular fingerprinting of Clostridium difficile isolates: pulsed-field gel electrophoresis versus amplified fragment length polymorphism. AB - Two molecular fingerprinting techniques, pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP), were used to investigate the epidemiological relatedness among Clostridium difficile isolates from suspected outbreaks in three general hospitals. Analysis by PFGE yielded inconclusive data as a result of extensive DNA degradation. Although this degradation could be prevented to a certain extent by the inclusion of thiourea in the electrophoresis buffer, the weak DNA banding patterns obtained in this way were still far from optimal. AFLP data were obtained by using fluorescently labeled PCR primers and analysis on an ABI PRISM automated DNA analysis platform. AFLP analysis yielded high resolution and highly reproducible DNA fingerprinting patterns from which the epidemiological relatedness among the isolates could easily be determined. AFLP results could be readily obtained within 24 h, whereas 3 to 4 days were routinely required to complete the lengthy PFGE protocol. AFLP clearly proved to be a much more fail-safe fingerprinting method for C. difficile isolates, especially for those isolates for which a standard PFGE procedure yielded inconclusive results due to DNA degradation. PMID- 11773101 TI - Phylogeny-based rapid identification of mycoplasmas and ureaplasmas from urethritis patients. AB - Some strains of mycoplasmas and ureaplasmas (family Mycoplasmataceae) are associated with nongonococcal urethritis (NGU) or other genitourinary infections. We have developed a rapid and reliable method of identifying the presence and prevalence of mycoplasmas and ureaplasmas in men with NGU. This method is based on the amplification of a part of the 16S rRNA gene by PCR and phylogenetic analysis. A portion of the 16S rRNA gene from 15 prototype strains was amplified with a set of common primers, and their nucleotides were sequenced. The nucleotide sequence of the V4 and V5 regions was analyzed by the neighbor-joining method. The 15 prototype strains were grouped into three distinct clusters, allowing us to clearly segregate the strains into distinct lineages. To determine the prevalence of these pathogens among patients with NGU, this protocol was tested with 148 urine samples. Amplifications were observed for 42 samples, and their nucleotide sequences were analyzed along with those of the 15 prototype strains. The phylogenetic tree thus constructed indicated that 15 of the 42 formed a cluster with Mycoplasma genitalium. Among the remaining specimens, 2 formed a cluster with Mycoplasma hominis, 19 with Ureaplasma urealyticum, and 5 with Ureaplasma parvum; the remaining sample contained both M. genitalium and U. urealyticum. This phylogeny-based identification of mycoplasmas and ureaplasmas provides not only a powerful tool for rapid diagnosis but also the basis for etiological studies of these pathogens. PMID- 11773102 TI - Simultaneous detection of measles virus, rubella virus, and parvovirus B19 by using multiplex PCR. AB - We describe here a multiplex reverse transcription-PCR (RTMNPCR) assay designed to detect and differentiate measles virus, rubella virus, and parvovirus B19. Serial dilution experiments with vaccine strains that compared cell culture isolation of measles in B95 cells and rubella in RK13 cells showed sensitivity rates of 0.004 50% tissue culture infective dose (TCID(50)) for measles virus and 0.04 TCID(50) for rubella virus. This RTMNPCR can detect as few as 10 molecules for measles virus and rubella virus and one molecule for parvovirus B19 in dilution experiments with plasmids containing inserts of the primary reaction amplification products. Five pharyngeal exudates from measles patients and 2 of 15 cerebrospinal fluid samples from measles-related encephalitis were found to be positive for measles virus by this RTMNPCR. A total of 3 of 27 pharyngeal exudates from vaccinated children and 2 pharyngeal exudates, plus one urine sample from a case of congenital rubella syndrome, were found to be positive for rubella virus by RTMNPCR, whereas 16 of 19 sera from patients with erythema infectiosum were determined to be positive for parvovirus B19 by RTMNPCR. In view of these results, we can assess that this method is a useful tool in the diagnosis of these three viruses and could be used as an effective surveillance tool in measles eradication programs. PMID- 11773103 TI - Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. AB - Hepatitis E virus (HEV) is endemic in many developing and some industrialized countries. It has been hypothesized that animals may be the source of infection. The recent identification of swine HEV in U.S. pigs and the demonstration of its ability to infect across species have lent credence to this hypothesis. To assess the potential risk of zoonotic HEV infection, we tested a total of 468 veterinarians working with swine (including 389 U.S. swine veterinarians) and 400 normal U.S. blood donors for immunoglobulin G anti-HEV. Recombinant capsid antigens from a U.S. strain of swine HEV and from a human HEV strain (Sar-55) were each used in an enzyme-linked immunosorbent assay. The anti-HEV prevalence assayed with the swine HEV antigen showed 97% concordance with that obtained with the human HEV antigen (kappa = 92%). Among the 295 swine veterinarians tested from the eight U.S. states (Minnesota, Indiana, Nebraska, Iowa, Illinois, Missouri, North Carolina, and Alabama) from which normal blood donor samples were available, 26% were positive with Sar-55 antigen and 23% were positive with swine HEV antigen. In contrast, 18% of the blood donors from the same eight U.S. states were positive with Sar-55 antigen and 17% were positive with swine HEV antigen. Swine veterinarians in the eight states were 1.51 times more likely when tested with swine HEV antigen (95% confidence interval, 1.03 to 2.20) and 1.46 times more likely when tested with Sar-55 antigen (95% confidence interval, 0.99 to 2.17) to be anti-HEV positive than normal blood donors. We did not find a difference in anti-HEV prevalence between veterinarians who reported having had a needle stick or cut and those who had not or between those who spent more time (> or = 80% of the time) and those who spent less time (< or = 20% of the time) working with pigs. Similarly, we did not find a difference in anti-HEV prevalence according to four job categories (academic, practicing, student, and industry veterinarians). There was a difference in anti-HEV prevalence in both swine veterinarians and blood donors among the eight selected states, with subjects from Minnesota six times more likely to be anti-HEV positive than those from Alabama. Age was not a factor in the observed differences from state to state. Anti-HEV prevalence in swine veterinarians and normal blood donors was age specific and paralleled increasing age. The results suggest that swine veterinarians may be at somewhat higher risk of HEV infection than are normal blood donors. PMID- 11773104 TI - BetalasEN: microdilution panel for identifying beta-lactamases present in isolates of Enterobacteriaceae. AB - A dried investigational use-only microdilution panel named betalasEN (a short named derived from the panel's purpose, to identify beta-lactamases in Enterobacteriaceae) containing 10 beta-lactam drugs with and without beta lactamase inhibitors was developed to identify beta-lactamases among clinical isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri, Citrobacter freundii group, Enterobacter spp., and Serratia marcescens. The MICs obtained with a collection of 383 organisms containing well characterized beta-lactamases were used to develop numeric codes and logic pathways for computerized analysis of results. The resultant logic pathways and betalasEN panel were then used to test and identify beta-lactamases among 885 isolates of Enterobacteriaceae recovered in cultures obtained at six different hospital laboratories across the United States. beta-Lactamases present in 801 (90.5%) of the 885 isolates were identified by betalasEN by using the existing logic pathways and codes or after minor modifications were made to the existing codes. The 84 strains that gave codes that betalasEN could not identify were collected, reidentified, and retested by using betalasEN. Three strains had been misidentified, 54 strains gave different codes upon repeat testing that could be identified by betalasEN, and 27 strains repeated new codes. The beta-lactamases in these strains were identified, and the new codes were added to the betalasEN logic pathways. These results indicate that betalasEN can identify clinically important beta-lactamases among most isolates of Enterobacteriaceae. The results also show that good quality control and attention to proper performance of the tests are essential to the correct performance of betalasEN. PMID- 11773105 TI - Detection of Chlamydia trachomatis by isothermal ramification amplification method: a feasibility study. AB - Chlamydia trachomatis is the leading cause of sexually transmitted disease in the United States. Effective screening for this agent can facilitate prompt treatment and prevent its sequelae. The recent introduction of liquid-based cytology has made possible the simultaneous screening of cervical intraepithelial lesions and detection of C. trachomatis in a single collection vial. In this study we determined whether cytological fluid could support DNA-based amplification for the detection of C. trachomatis. Three methods were compared, including ramification amplification (RAM), real-time PCR with molecular beacon, and Abbott's ligase chain reaction (LCx). RAM is a novel, recently introduced, isothermal DNA amplification technique that utilizes a circular probe for target detection and achieves exponential amplification through the mechanism of primer extension, strand displacement, and ramification. Our results show that RAM can detect as few as 10 C. trachomatis elementary bodies in less than 2 h, comparable to results with real-time PCR. Thirty clinical specimens collected in PreservCyt solution were tested by LCx, real-time PCR, and RAM. Among 30 specimens, 15 were positive by PCR and LCx and 14 were positive by RAM. One specimen missed by RAM had an inadequate amount of residual cellular material. Our results show that nucleic acid amplification methods can serve to detect C. trachomatis and presumably other sexually transmitted agents in cytological fluid and that the RAM assay can be an alternative to PCR and LCx because of its simplicity and isothermal amplification. PMID- 11773106 TI - Molecular epidemiology of astrovirus infection in Barcelona, Spain. AB - A 3-year study involving 2,347 gastroenteritis samples was conducted to determine the prevalence, time distribution, and medical significance of human astrovirus infection in Barcelona, Spain. The overall incidence of astrovirus was found to be 4.9%. Mixed infections with other enteric agents were detected in 17.2% of all astrovirus-positive samples. During the 3-year period, the highest astrovirus incidence was reported in the winter months, although infections also occurred in summer. The peak detection rate was observed in children between 2 and 4 years of age. Overall, HAstV-1 was the most prevalent type, followed by HAstV-4, HAstV-3, HAstV-8, and HAstV-2. HAstV-5, HAstV-6, and HAstV-7 were not detected during these 3 years. From our serotype data for each age group, we observed that HAstV 1, HAstV-2, and HAstV-3 affected mostly children younger than 3 years of age, while HAstV-4 and HAstV-8 had a greater impact in older children. Genetic variability was analyzed between astroviruses isolated in Barcelona and strains isolated in other parts of the world. A fourth lineage was described for HAstV-1, most likely due to the large number of assayed samples, which may also explain the high level of genetic variability observed in the astrovirus isolates. PMID- 11773107 TI - Molecular and epidemiological analyses of human adenovirus type 7 strains isolated from the 1995 nationwide outbreak in Japan. AB - The adenovirus type 7 (Ad7) isolates from the 1995 nationwide outbreak in Japan were genetically and seroepidemiologically analyzed in comparison with Japanese Ad7 strains isolated before 1995 to determine their genome type and to speculate on their origin and causative factors of the outbreak. Twenty-six Ad7 isolates from the outbreak were identified by restriction enzyme analysis as the Ad7d2 genome type, while 22 Ad7 strains sporadically isolated in Japan before 1995 were identified as Ad7d. Partial nucleotide sequencing of the E3 region of Ad7d2 revealed a nucleotide substitution of G to A at position 265, resulting in the absence of the BstEII site and making Ad7d2 distinct from Ad7d. In Hiroshima City, Japan, no Ad7 was isolated from 1982 to 1994, but 43 and 50 Ad7 strains were isolated in 1995 and 1996, respectively. A seroepidemiological study of 251 serum samples collected in 1989 in Hiroshima City showed that only 2.8% of the samples were positive for Ad7. These results indicate that the 1995 outbreak of Ad7 in Japan was caused by the Ad7d2 genome type, which might have been introduced from outside Japan. The results also suggest that the low mass immunity in Japan was critical for the outbreak and that the mutation in the E3 region in Ad7d2 may have influenced transmission. PMID- 11773108 TI - Genomic diversity of group A rotavirus strains infecting humans in eastern India. AB - Between 1998 and 2000, a total of 266 samples were found positive for group A rotaviruses by RNA electrophoresis. Samples were collected from patients admitted to two leading hospitals in Calcutta. Serotyping could be done only with 22% of the positive samples, leaving 78% untypeable. The G (VP7 genotypes) and P (VP4 genotypes) types were determined for 159 samples by reverse transcription and multiplex PCR. The predominant genotype was G1P[8] (20%), followed by G2P[4] (15%) and G4P[8] (6%). A number of uncommon genotypes, G1P[4] (4%), G2P[8] (2.5%), G2P[6] (0.6%), G4P[4] (2.5%), and G4P[6] (1.25%), were also detected during this study period. Twenty two percent of specimens showed mixed infections, 38 (24%) of the total samples remained untypeable for either VP7 or VP4, while only 4 (2.5%) of the samples were untypeable for both genes. Eleven specimens collected from Manipur were also genotyped and revealed a very high degree of genomic reassortment. PMID- 11773109 TI - Multicenter evaluation of fully automated BACTEC Mycobacteria Growth Indicator Tube 960 system for susceptibility testing of Mycobacterium tuberculosis. AB - The reliability of the BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system for testing of Mycobacterium tuberculosis susceptibility to the three front-line drugs (isoniazid [INH], rifampin [RIF], and ethambutol [EMB]) plus streptomycin (STR) was compared to that of the BACTEC 460 TB system. The proportion method was used to resolve discrepant results by an independent arbiter. One hundred and ten strains were tested with an overall agreement of 93.5%. Discrepant results were obtained for seven strains (6.4%) with INH (resistant by BACTEC MGIT 960; susceptible by BACTEC 460 TB), for one strain (0.9%) with RIF (resistant by BACTEC MGIT 960; susceptible by BACTEC 460 TB), for seven strains (6.4%) with EMB (six resistant by BACTEC MGIT 960 and susceptible by BACTEC 460 TB; one susceptible by BACTEC MGIT 960 and resistant by BACTEC 460 TB), and for 19 strains (17.3%) with STR (resistant by BACTEC MGIT 960 and susceptible by BACTEC 460 TB). After resolution of discrepant results, the sensitivity of the BACTEC MGIT 960 system was 100% for all four drugs and specificity ranged from 89.8% for STR to 100% for RIF. Turnaround times were 4.6 to 11.7 days (median, 6.5 days) for BACTEC MGIT 960 and 4.0 to 10.0 days (median, 7.0 days) for BACTEC 460 TB. These data demonstrate that the fully automated and nonradiometric BACTEC MGIT 960 system is an accurate method for rapid susceptibility testing of M. tuberculosis. PMID- 11773110 TI - Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery. AB - During pregnancy, Plasmodium falciparum infection of the placenta frequently occurs in the absence of parasites in peripheral blood. We investigated the abilities of the OptiMAL rapid immunochromatographic strip test for P. falciparum lactate dehydrogenase and species-specific PCR performed on peripheral blood to detect placental infection or malaria-associated low birth weight. Of 509 Malawian women screened by microscopy, 76 had malaria infection. Among these 509 women, the frequency of peripheral blood parasitemia was low. The OptiMAL test gave positive results in 37 of 171 women tested (one of whom had placental but not peripheral blood parasitemia) and had sensitivities of 71% for peripheral parasitemia and 38% for placental parasitemia compared to the microscopy values. The specificity for peripheral parasitemia was 94%. In 135 women, PCR had sensitivities of 94% for peripheral blood malaria detected by microscopy and 72% for placental infection. In samples examined by PCR, the prevalence of malaria in peripheral blood increased from 26.7% by microscopy to 51.9%. Women with placental malaria and women with malaria in peripheral blood samples by microscopy or OptiMAL testing, but not women with malaria detected only by PCR, had lower-birth-weight babies than did women without malaria by these criteria. Positive results by PCR in the absence of microscopic parasitemia were not associated with low birth weight. Neither OptiMAL nor PCR testing of peripheral blood is adequately sensitive to detect all placental malaria infection, but a positive result by OptiMAL testing identifies women with a high proportion of low birth-weight babies. PMID- 11773111 TI - Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae. AB - A geographical analysis of how commonly prescribed oral antibiotics are quantitatively and qualitatively responsible for the different local rates of erythromycin and penicillin resistance in Streptococcus pneumoniae in Spain is presented. From 1998 to 1999 a multicenter surveillance study yielded 1,684 consecutive S. pneumoniae isolates from community-acquired respiratory infections. Data on antibiotic sales in the retail market for the same period were gathered, and the corresponding defined doses per 1,000 inhabitants per day were calculated. Macrolides and beta-lactams were considered separately. Macrolides were subdivided into thrice-, twice-, and once-a-day macrolides, and beta-lactams were split into aminopenicillins and cephalosporins. Univariate Spearman nonparametric coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were entered into several multiple lineal regression models. Ample variation in both resistance rates and antibiotic consumption was seen. Multivariate analyses showed that integrated consumption of both macrolides and beta-lactams accounted well for erythromycin (R(2) = 0.722; P = 0.002) and penicillin (R(2) = 0.706; P = 0.002) resistance. Macrolides were more important drivers for local differences in both erythromycin and penicillin resistance than beta-lactams were. Consumption of once-a-day macrolides was key for local erythromycin resistance variations. Cephalosporins were slightly more important penicillin resistance drivers than aminopenicillins were. PMID- 11773112 TI - Evaluation of four commercial immunoglobulin G (IgG)- and IgM-specific enzyme immunoassays for diagnosis of Mycoplasma pneumoniae infections. AB - The four following commercially available enzyme immunoassays (EIAs) were assessed and compared for their performance in detecting Mycoplasma pneumoniae immunoglobulin G (IgG)- and IgM-specific antibodies Platelia EIA, ImmunoWELL M. pneumoniae ELISA IgG and IgM, ETI-MP-IgG and IgM EIAs and Biotest anti-M. pneumoniae IgG and IgM ELISA (referred to herein as EIA-Platelia, EIA-BMD, EIA Sorin, and EIA-Biotest). Three groups of patients were investigated: 39 patients (27 children and 12 adults) with respiratory infections who tested positive by PCR for M. pneumoniae in respiratory specimens (group I; 52 serum samples), 61 healthy children and adults (group II; 61 serum samples), and 20 patients with rheumatoid factor or antinuclear antibodies, or who tested positive for antiviral IgM (group III; 20 serum samples). In group III, the IgM specificity for EIA Platelia, EIA-BMD, EIA-Biotest, and EIA-Sorin was 100, 90, 65, and 25%, respectively. In the children from group I, the four EIAs had similar IgM sensitivities (89 to 92%); the sensitivity for IgG was greater with EIA-BMD and EIA-Biotest than with EIA-Platelia and EIA-Sorin (66 and 78% versus 55 and 52%, respectively). In adult patients from group I, 9 to 10 serum samples were positive for IgG with a concordant sensitivity of 75 to 83% between the four EIAs but a striking difference in IgM sensitivity: 16% by EIA-Platelia and EIA-BMD, 50% by EIA-Biotest, and 58% by EIA-Sorin. Discrepant and unexpected results were observed in IgM detection from control healthy patients using EIA-Sorin and EIA Biotest, confirming the lack of specificity of these two EIAs and making them inaccurate for routine diagnosis. A good concordance of IgG seroprevalence in healthy adults was found between the four EIAs (66 to 70%), though this concordance was lower with EIA-Platelia (43%). In healthy children, EIA-BMD and EIA-Biotest gave a higher IgG seroprevalence than EIA-Sorin and EIA-Platelia (45% each for the former compared to 17 and 20%, respectively, for the latter). These results confirm that the IgM EIA serology test is a valuable tool for the early diagnosis of M. pneumoniae infections in children, as long as the EIA used is specific. In adults, the difficult interpretation of EIAs suggests that paired sera, combined with PCR detection on respiratory tract specimens collected on admission of patient, should be required for accurate diagnosis. PMID- 11773113 TI - Pandemic spread of cholera: genetic diversity and relationships within the seventh pandemic clone of Vibrio cholerae determined by amplified fragment length polymorphism. AB - The seventh cholera pandemic started in 1961 and continues today. A collection of 45 seventh pandemic isolates of V. cholerae sampled over a 33-year period were analyzed by amplified fragment length polymorphism (AFLP) fingerprinting. All but four pairs and one set of three isolates were distinguished. AFLP revealed far more variation than ribotyping, which was until now the most useful method of revealing variation within the pandemic clone. Unfortunately, the ribotype variation observed is mainly due to recombination between the multiple copies of the rrn genes (R. Lan and P. R. Reeves, Microbiology 144:1213-1221, 1998), which makes changes susceptible to repeat occurrences and reversion. This AFLP study shows that particularly for the common ribotypes G and H, such events have indeed occurred. AFLP grouped most of the 45 isolates into two clusters. Cluster I consists mainly of strains from the 1960s and 1970s, while cluster II contains mainly strains from the 1980s and 1990s, revealing a temporal pattern of change in the clone. This is best seen in the relationships of the strains from Africa, which correlate with the epidemiology of epidemics on that continent. The data confirm independent introductions to Africa during the 1970s outbreak and reveal several other African introductions. In the 1991 cholera upsurge, isolates from the Southern and Eastern African epidemic focus are markedly different from those from the West African epidemic focus. An isolate from 1987 in Algeria was identical to the West epidemic isolates, suggesting that the strain was present in Africa at least 3 years before causing large outbreaks. These observations have major implications for our understanding of cholera epidemiology. PMID- 11773114 TI - Molecular identification of enterovirus by analyzing a partial VP1 genomic region with different methods. AB - VP1 is the most suitable region for use in the identification of enterovirus. Although VP1 sequencing methods may vary, it is necessary to agree on a common strategy of sequence analysis. Identification of a strain type may be achieved by three different approaches: pairwise sequence alignment, multiple-sequence alignment, and phylogenetic inference. Other methods are also available, but they are not simple enough to be performed at a virology laboratory. The performances of these methods were evaluated with nucleotide and protein sequences obtained from 32 original samples, 8 enterovirus isolates, and 64 GenBank sequences. Pairwise sequence alignment methods had very different results. The DNASTAR package identified only 28.8% of enterovirus strains, while the Genetics Computer Group package identified 50.0 or 72.1% of enterovirus strains when nucleotide or amino acid sequences were analyzed, respectively. Multiple-sequence alignment methods identified 94.2% (Clustal W program) or 92.3% (Pileup program) of the enterovirus strains, while the phylogenetic method increased this rate to 99.0%. Comparative evaluation of these analysis methods showed that the Clustal W program (version 1.81), a freely available multiple-sequence alignment program, presented one of the best performances when used with the correct criteria. Other commercial and expensive programs did not achieve the same performances, making them less suitable for molecular typing of enteroviruses. Finally, although phylogenetic inference is the most demanding method in terms of knowledge of the user, it remained the best option analyzed. PMID- 11773115 TI - Recombinant assay for serodiagnosis of Lyme disease regardless of OspA vaccination status. AB - All current seroassays using cultured Borrelia burgdorferi as their antigen source have been rendered obsolete by the recombinant OspA Lyme disease vaccine. OspA is the major outer surface protein expressed in cultured B. burgdorferi, and any seroassay that uses whole organisms as its antigen source cannot differentiate between subjects who received the vaccine and those who were naturally infected. We developed a new sensitive and specific enzyme-linked immunosorbent assay (ELISA) utilizing recombinant chimeric borrelia proteins devoid of OspA (rNon-OspA) that can be used to detect antibodies to diagnostically important B. burgdorferi antigens in both OspA-vaccinated and nonvaccinated individuals. We tested sera from patients with Lyme disease and with conditions associated with false-positive serologies, OspA-vaccinated individuals, and healthy high-risk workers from an area of endemicity and normal sera from individuals from areas of nonendemicity. The rNon-OspA test was compared with two commercially available whole-cell immunoassays. The rNon-OspA assay is as sensitive and specific as the whole-cell assay (P > 0.05) for detection of anti-B. burgdorferi antibodies. However, the rNon-OspA assay can differentiate between populations comprised of naturally infected and OspA vaccinated individuals (P < 0.05). Our data demonstrate that this new sensitive rNon-OspA ELISA can be used for the laboratory detection of B. burgdorferi antibodies regardless of vaccination status and could replace existing serologic assays for Lyme disease. PMID- 11773116 TI - Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. AB - The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis. PMID- 11773117 TI - Evaluation of a novel heminested PCR assay based on the phosphoglucosamine mutase gene for detection of Helicobacter pylori in saliva and dental plaque. AB - A novel heminested PCR protocol was developed for the specific detection of Helicobacter pylori at low copy numbers. A set of primers specific for the phosphoglucosamine mutase gene (glmM) of H. pylori produced a 765-bp fragment that was used as template for the heminested primer pair delineating a 496-bp fragment. By using agarose gel electrophoresis for detection of the heminested PCR-amplified products, amplification of H. pylori genomic DNA was achieved at concentrations as low as 0.1 pg, equivalent to 5 x 10(2) bacteria. A study was subsequently undertaken to evaluate the heminested PCR for detection of H. pylori in dental plaque and saliva. Specimens collected from 58 individuals were cultured, and PCR was subsequently performed on the oral cultures. Identification of H. pylori in the same series of saliva and dental plaque specimens was carried out with PCR using a primer pair specific for the H. pylori urease B gene and by the heminested PCR assay. The identity of the amplified products was confirmed by DNA sequencing. Our results demonstrate that the heminested PCR assay was specific for detection of H. pylori, yielding no false-positive results, and that H. pylori had a low prevalence (approximately 3%) in specimens obtained from the oral cavity. PMID- 11773118 TI - Comparison of six PCR methods using peripheral blood for detection of canine visceral leishmaniasis. AB - The objectives of this study were to compare the sensitivities and reliabilities of different PCR methods for the diagnosis and epidemiological study of canine visceral leishmaniasis (CVL) using dog blood. We chose to work with peripheral blood, as this type of sampling is noninvasive, straightforward, and easy to repeat. Six PCR methods were compared: three primer pairs target genomic DNA, and the other three target kinetoplast (mitochondrial) DNA. Sensitivity, specificity, reproducibility, and ease of interpretation without hybridization were evaluated for each method. The assessment was first performed using artificial samples. All methods could detect less than one parasite per reaction tube. However, the sensitivities varied among the different methods by a factor of 500 on purified cultivated parasites and by a factor of 10,000 on seeded dog blood samples (i.e., from 10 to 10(-3) parasite per ml of blood for the latter). Only four methods were found sufficiently reliable for the diagnosis of CVL. They were tested on 37 dogs living in an area of endemicity and grouped according to clinical status and specific serology. Only the two methods targeting kinetoplast DNA (K13A-K13B and RV1-RV2) could detect the parasite in 100% of symptomatic infected dogs. Similarly, all seropositive dogs were found PCR positive by these methods versus 62% by the genomic-DNA-based methods. Finally, these kinetoplast-based methods proved clearly superior to the others in the detection of Leishmania in asymptomatic dogs. Our data allow the discussion of the advantages and drawbacks of highly sensitive versus moderately sensitive PCR methods in diagnosis and prevalence studies of CVL. PMID- 11773119 TI - Serotype identification of group B streptococci by PCR and sequencing. AB - Group B streptococcus (GBS; Streptococcus agalactiae) is the most common cause of neonatal and obstetric sepsis and is an increasingly important cause of septicemia in elderly individuals and immunocompromised patients. Ongoing surveillance to monitor GBS serotype distribution will be needed to guide the development and use of GBS conjugate vaccines. We designed sequencing primers based on the previously published sequences of the capsular polysaccharide (cps) gene clusters to further define partial cps gene clusters for eight of the nine GBS serotypes (serotypes Ia to VII). Subsequently, we designed and evaluated primers to identify serotypes Ia, Ib, III, IV, V, and VI directly by PCR and all eight serotypes (serotypes Ia to VII) by sequence heterogeneity. A total of 206 clinical GBS isolates were used to compare our molecular serotype (MS) identification method with conventional serotyping (CS). All clinical isolates were assigned an MS, whereas 188 of 206 (91.3%) were assigned a serotype by use of antisera. A small number of isolates (serosubtypes III-3 and III-4) showed different serotype specificities between PCR and sequencing, but the PCR results correlated with those obtained by CS. The overall agreement between the MS identification method and CS for isolates for which results of both tests were available was 100% (188 of 188 isolates). The MS identification method is a specific and practical alternative to conventional GBS serotyping and will facilitate epidemiological studies. PMID- 11773120 TI - Phenotypic variation of Helicobacter pylori isolates from geographically distinct regions detected by lectin typing. AB - A total of 309 Helicobacter pylori isolates from 18 different countries were analyzed with a previously developed lectin typing system. The system was developed by using a proteolytic pretreatment to enhance the carbohydrate fraction of the sample. Four lectins from Ulex europaeus, Lotus tetragonolobus, Erythrina cristigali, and Triticum vulgaris were used to type the strains. The lectins were chosen for their specificities for sugars commonly encountered in the lipopolysaccharide of H. pylori. The isolates were received from their parent institutions as pellets of biomass and were typed at one of three centers (in Ireland, Sweden, and Estonia). All 16 possible lectin reaction patterns were observed in the study, with the isolates with the predominant pattern exhibiting reactions with all the lectins in the panel. For European patients suffering from gastritis, an association was noted between lectin reaction pattern MH4 and atrophic chronic gastritis; isolates with lectin reaction pattern MH4 were isolated from patients with atrophic chronic gastritis, whereas isolates with this pattern were not isolated from patients with chronic gastritis (P = 0.0006). In addition, statistically significant relationships were noted between the lectin reaction pattern and the associated pathology of isolates from the Swedish population. Isolates with patterns MH13 and MH16, which had low lectin reactivities, correlated with nonulcer disease (P = 0.0025 and P = 0.0002, respectively), and all four isolates from adenocarcinoma patients were characterized as possessing reaction pattern MH16. In contrast, isolates with lectin reaction patterns MH1 and MH10, which had high lectin reactivities, were associated with ulcer disease (P = 0.046 and P = 0.0022, respectively). PMID- 11773121 TI - Human cytomegalovirus and human umbilical vein endothelial cells: restriction of primary isolation to blood samples and susceptibilities of clinical isolates from other sources to adaptation. AB - In immunocompromised patients with disseminated infection, human cytomegalovirus (HCMV) is widespread in the microvascular endothelium of multiple organs. Human umbilical vein endothelial cells (HUVEC) were used in parallel to human embryonic lung fibroblasts (HELF) to recover HCMV from blood samples of immunocompromised patients. Using the shell vial technique, comparable median numbers of p72 positive HUVEC and HELF cells were found with the 26 HCMV-positive buffy coat samples out of 150 examined. Analysis of other clinical samples inoculated as controls revealed, in the presence of highly infected HELF monolayers, either the presence of very few infected HUVEC with urine specimens (n = 10 samples) or the lack of infected HUVEC with throat washes (n = 3) or amniotic fluid samples (n = 2). Thus, peripheral blood leukocytes (PBL) appear essential for primary isolation of HCMV in HUVEC. In this respect, HCMV strains, recovered from clinical samples other than buffy coats in HELF only, could be readily adapted to growth in HUVEC by coculturing PBL from healthy blood donors with infected HELF and then inoculating infected PBL onto HUVEC. Recently elucidated mechanisms of interaction of leukocytes and HUVEC with bidirectional transfer of virus seem to provide the basis for the restriction of HCMV primary isolation in HUVEC to blood samples. However, virus strains recovered from only HELF could be adapted to growth in HUVEC when inoculated with HELF-derived (either cell-associated or cell free) HCMV strains upon primary isolation. In conclusion, due to the in vitro selection of virus variants provided with both PBL tropism and HUVEC tropism, HCMV recovery in HUVEC is PBL mediated and substantially restricted to blood samples. Lack of HCMV recovery in HUVEC from clinical samples other than blood leads to the assumption that epithelial cells, such as urinary, amniotic, or pharyngeal cells, do not possess adequate adhesion molecules to establish close contacts with HUVEC. PMID- 11773124 TI - Application of real-time fluorescent PCR for quantitative assessment of Neospora caninum infections in organotypic slice cultures of rat central nervous system tissue. AB - The previously described Nc5-specific PCR test for the diagnosis of Neospora caninum infections was used to develop a quantitative PCR assay which allows the determination of infection intensities within different experimental and diagnostic sample groups. The quantitative PCR was performed by using a dual fluorescent hybridization probe system and the LightCycler Instrument for online detection of amplified DNA. This assay was successfully applied for demonstrating the parasite proliferation kinetics in organotypic slice cultures of rat brain which were infected in vitro with N. caninum tachyzoites. This PCR-based method of parasite quantitation with organotypic brain tissue samples can be regarded as a novel ex vivo approach for exploring different aspects of cerebral N. caninum infection. PMID- 11773122 TI - Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status. AB - Since the associations between Helicobacter pylori genotype and disease differ in Asia and the West, we investigated the correlation between HP0638, encoding an outer membrane protein, and potential markers of virulence (cagA, vacA, and iceA). For 109 strains from nine countries, the status of cagA, vacA, and iceA was determined by PCR and/or a line probe assay. We also studied 18 strains from 8 patients (parents and 6 daughters) from a Dutch family and paired strains collected on average 8 years apart from 11 patients. When the HP0638 signal sequences were amplified by PCR and DNA sequence determinations were performed, 89 (96%) of 93 cagA-positive strains had HP0638 in frame, versus none (0%) of 16 cagA-negative strains (P < 0.001). Among strains in which HP0638 was in frame, a six-CT dinucleotide repeat pattern was dominant in Western countries (23 of 33 strains [70%]), while a pattern of three CT repeats with another CT after four T's (3 + 1-CT-repeat pattern) was dominant in East Asia (31 of 46 strains [67%]); however, specific CT repeat patterns did not correlate with clinical outcome. HP0638 phylogenetic trees also showed geographic characters. The HP0638 frame status and CT dinucleotide repeat patterns were identical for 9 of 11 pairs of strains obtained on average 8 years apart from individuals and the 15 strains obtained from the mother and all six daughters. Thus, HP0638 frame status and cagA status are strongly correlated. The CT dinucleotide repeat pattern in the putative HP0638 signal sequence has geographic characters and appears stable in particular patients and families over a period of years. Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes. PMID- 11773123 TI - Rapid identification of Staphylococcus aureus directly from blood cultures by fluorescence in situ hybridization with peptide nucleic acid probes. AB - A new fluorescence in situ hybridization (FISH) method with peptide nucleic acid (PNA) probes for identification of Staphylococcus aureus directly from positive blood culture bottles that contain gram-positive cocci in clusters (GPCC) is described. The test (the S. aureus PNA FISH assay) is based on a fluorescein labeled PNA probe that targets a species-specific sequence of the 16S rRNA of S. aureus. Evaluations with 17 reference strains and 48 clinical isolates, including methicillin-resistant and methicillin-susceptible S. aureus species, coagulase negative Staphylococcus species, and other clinically relevant and phylogenetically related bacteria and yeast species, showed that the assay had 100% sensitivity and 96% specificity. Clinical trials with 87 blood cultures positive for GPCC correctly identified 36 of 37 (97%) of the S. aureus-positive cultures identified by standard microbiological methods. The positive and negative predictive values were 100 and 98%, respectively. It is concluded that this rapid method (2.5 h) for identification of S. aureus directly from blood culture bottles that contain GPCC offers important information for optimal antibiotic therapy. PMID- 11773125 TI - Molecular typing of Treponema pallidum in South Africa: cross-sectional studies. AB - We evaluated a molecular subtyping system for Treponema pallidum for its ability to differentiate between strains obtained from male patients with primary syphilis in South Africa. Of 201 T. pallidum-positive specimens, 161 were typeable, revealing 35 subtypes. The unique subtypes identified in Durban, Cape Town, and Carletonville and the total number of subtypes suggested that the strain population was very diverse and varied geographically. PMID- 11773126 TI - Assessment of clarithromycin-resistant Helicobacter pylori among patients in Shanghai and Guangzhou, China, by primer-mismatch PCR. AB - Of 96 Helicobacter pylori isolates from patients in Shanghai and Guangzhou, China, 5 had the A2143G 23S rRNA mutation as determined by primer-mismatch PCR and were resistant to clarithromycin by the E-test. The remaining isolates were primer-mismatch PCR negative and susceptible to clarithromycin. The conclusion is that the prevalence of clarithromycin-resistant H. pylori isolates among these Chinese patients is 5%. PMID- 11773127 TI - Accurate, noninvasive detection of Helicobacter pylori DNA from stool samples: potential usefulness for monitoring treatment. AB - A novel DNA assay demonstrating sensitive and accurate detection of Helicobacter pylori from stool samples is reported. Moreover, in three individuals tested for therapeutic response, the assay showed the disappearance of H. pylori DNA during treatment. Thus, this noninvasive molecular biology-based assay has the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori DNA. PMID- 11773128 TI - Identification by 16S rRNA gene sequencing of Lactobacillus salivarius bacteremic cholecystitis. AB - An anaerobic, nonsporulating, gram-positive bacterium was isolated from blood and bile pus cultures of a 70-year-old man with bacteremic acute cholecystitis. The API 20A system showed that it was 70% Actinomyces naeslundii and 30% Bifidobacterium species, whereas the Vitek ANI system and the ATB ID32A Expression system showed that it was "unidentified." The 16S rRNA gene of the strain was amplified and sequenced. There were 3 base differences between the nucleotide sequence of the isolate and that of Lactobacillus salivarius subsp. salivarius or L. salivarius subsp. salicinius, indicating that the isolate was a strain of L. salivarius. The patient responded to cholecystectomy and a 2-week course of antibiotic treatment. Identification of the organism in the present study was important because the duration of antibiotic therapy would have been entirely different depending on the organism. If the bacterium had been identified as Actinomyces, penicillin for 6 months would have been the regimen of choice. However, it was Lactobacillus, and a 2-week course of antibiotic was sufficient. PMID- 11773129 TI - Active copper- and zinc-containing superoxide dismutase in the cryptic genospecies of Haemophilus causing urogenital and neonatal infections discriminates them from Haemophilus influenzae sensu stricto. AB - The presence of active copper- and zinc-containing superoxide dismutase in isolates of the cryptic genospecies of Haemophilus, responsible for urogenital, neonatal, and mother-infant infections, can be used as a biochemical marker to discriminate them from H. influenzae sensu stricto strains. PMID- 11773130 TI - Direct detection and characterization of Shiga toxigenic Escherichia coli by multiplex PCR for stx1, stx2, eae, ehxA, and saa. AB - We recently described a novel megaplasmid-encoded adhesin produced by certain Shiga toxigenic Escherichia coli (STEC) strains that lack the locus for enterocyte effacement (LEE) pathogenicity island. This adhesin, designated Saa (STEC autoagglutinating adhesin), may be a marker for a subset of LEE-negative STEC strains capable of causing severe gastrointestinal and systemic diseases in humans. In this study, we developed a pentavalent PCR assay for the detection of saa as well as other proven and putative STEC virulence genes (stx1, stx2, eae, and ehxA). The five primer pairs used in the assay do not interfere with each other and generate amplification products of 119, 180, 255, 384, and 534 bp. PMID- 11773131 TI - Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil. AB - Penicillin-nonsusceptible strains were isolated from 15% of 303 individuals with pneumococcal meningitis identified during a 4-year surveillance study in Salvador, Brazil. The estimated rate of coverage of the seven-valent conjugate vaccine was 74% among patients <5 years of age and 94% among those infected with nonsusceptible isolates, indicating that the use of conjugate vaccines may be an approach to the control of emerging penicillin resistance in Brazil. PMID- 11773132 TI - Molecular characterization of group A Streptococcus strains isolated during a scarlet fever outbreak. AB - Forty group A streptococcus (GAS) isolates, recovered during a scarlet fever outbreak, were grouped based on their DdeI restriction profiles from emm amplicons. Twenty-seven isolates were identified by sequencing as emm2. The emm2 isolates showed the speA1, speB1, and speC1 alleles. Isolation of this GAS type from scarlet fever outbreaks is uncommon. PMID- 11773133 TI - Evaluation of a strand displacement amplification assay (BD ProbeTec-SDA) for detection of Neisseria gonorrhoeae in urine specimens. AB - The performance of a strand displacement amplification assay (the BDProbeTec-SDA assay) in detecting Neisseria gonorrhoeae in urine specimens was evaluated. When performed under stringent quality control conditions, the BDProbeTec-SDA assay is a sensitive, specific, and efficient method for the screening of large numbers of noninvasively obtained specimens. Because the predictive value of an assay is a function of the prevalence of the disease, culture confirmation is needed for samples with positive results from populations in which the prevalence of a disease is low or in situations in which false-positive results may have important medical, psychosocial, or medicolegal consequences. PMID- 11773134 TI - Prevalence of the pandemic genotype of Vibrio parahaemolyticus in Dhaka, Bangladesh, and significance of its distribution across different serotypes. AB - Sixty-six strains of Vibrio parahaemolyticus belonging to 14 serotypes were isolated from hospitalized patients in Dhaka, Bangladesh, from January 1998 to December 2000. Among these, 48 strains belonging to four serotypes had the pandemic genotype and possessed the tdh gene. A marker (open reading frame ORF8) for a filamentous phage previously thought to correspond to the pandemic genotype was found to have a poor correlation with the pandemic genotype. PMID- 11773135 TI - Comparison of real-time, quantitative PCR with molecular beacons to nested PCR and culture methods for detection of Mycobacterium avium subsp. paratuberculosis in bovine fecal samples. AB - An automated PCR with fluorescent probes (molecular beacons) detected Mycobacterium avium subsp. paratuberculosis in bovine feces. When the PCR was compared with culture in testing 41 fecal samples, kappa scores of 0.94 to 0.96, a sensitivity of 93 to 96%, and a specificity of 92% were obtained. Results were quantitated by using a standard curve derived from a plasmid containing IS900. A minimum quantity of 1.7 x 10(-4) pg of DNA, correlating to 1 to 8 CFU, was detected. PMID- 11773136 TI - Reaction difference rule for phage typing of Staphylococcus aureus at 100 times the routine test dilution. AB - Duplicate phage typing tests of 150 isolates of methicillin-sensitive and resistant Staphylococcus aureus at 100 times the routine test dilution showed that the existing reaction difference rule remains satisfactory when isolates are tested on the same day; i.e., two or more reactions must differ before isolates should be considered distinct. However, if typing is done on different days, a three-reaction-difference rule is needed. PMID- 11773137 TI - Characterization of enteropathogenic and enteroaggregative Escherichia coli isolated from diarrheal outbreaks. AB - Virulence characteristics of diarrheal outbreak-associated Escherichia coli O55:NM, O126:NM, and O111:NM were examined. The E. coli O55:NM strains were atypical enteropathogenic E. coli (EPEC), while the E. coli O126:NM and O111:NM strains should be classified as enteroaggregative E. coli (EAggEC). The contributions of EPEC and EAggEC to the human disease burden in Japan might be significantly greater than is currently appreciated. PMID- 11773138 TI - Association of cagA and vacA genotypes of Helicobacter pylori with gastric diseases in Estonia. AB - Gastric biopsy specimens from 156 adult patients from southern Estonia suffering from chronic gastritis, peptic ulcer disease, and perforated peptic ulcer were analyzed by PCR. The cagA gene was evenly distributed throughout 87% of the specimens from the patients with the different gastric diseases. The presence of the cagA gene correlated with that of vacA signal sequence type s1a (99%). However, no clear differences were found in the distribution of cagA and vacA genotypes among patients in Estonia with severe perforated peptic ulcer, uncomplicated peptic ulcer, or chronic gastritis. PMID- 11773139 TI - Antibiotic-resistant cell-detaching Escherichia coli strains from Nigerian children. AB - The properties of 23 cell-detaching Escherichia coli strains that were isolated from stool specimens in Nigeria are described. Common properties of the strains included the presence of genes encoding alpha-hemolysin (100%), pyelonephritis associated pili (100%), and cytotoxic necrotizing factor 1 (70%) as well as lactose negativity (70%) and multiple antibiotic resistance (74%). Antibiotic resistance was shown in most cases to be transferable and associated with the presence of class 1 integrons. Phenotypic properties and pulsed-field gel electrophoresis analysis demonstrated that the majority of the strains, particularly multiply resistant, lactose-negative O4:H40 strains, were closely related. Multiply-resistant cell-detaching E. coli strains may represent an important reservoir for antibiotic resistance genes. PMID- 11773140 TI - Diagnosis of placental malaria. AB - In a group of 596 delivering Ghanaian women, the sensitivities of peripheral blood thick film microscopy, ICT Malaria P.f/P.v test, and PCR in detecting microscopically confirmed placental Plasmodium falciparum infection were 42, 80, and 97%, respectively. In addition to the gross underestimation of placental malaria by peripheral blood film microscopy, submicroscopic infections were found to be a risk factor for maternal anemia. PMID- 11773141 TI - Primary meningoencephalitis by Naegleria fowleri: first reported case from Mangalore, South India. AB - A fatal case of primary amebic meningoencephalitis (PAM) in a 5-month-old infant is described. The disease may have been contracted during bathing. The source of water was from an artificial well. The clinical presentation, the isolation of the ameba from the cerebrospinal fluid, the poor response to amphotericin B, and the ultimate fatal outcome are all consistent with the diagnosis of PAM. On the basis of its ability to grow at temperatures above 30 degrees C, the morphology of the trophozoite, and the presence of flagellate forms, the ameba was identified as Naegleria fowleri. Pathogenic N. fowleri amebae were recovered from samples of water from the well. To our knowledge this case represents the second case of PAM in an infant in the absence of the history of swimming. PMID- 11773142 TI - Catheter-related bacteremia due to Kocuria kristinae in a patient with ovarian cancer. AB - We report on the first case of a catheter-related recurrent bacteremia caused by Kocuria kristinae, a gram-positive microorganism belonging to the family Micrococcaceae, in a 51-year-old woman with ovarian cancer. This unusual pathogen may cause opportunistic infections in patients with severe underlying diseases. PMID- 11773143 TI - Alternative strategies for confirmation of human immunodeficiency virus infection require judicious use. PMID- 11773144 TI - Investigation of the presence of recombinant polioviruses in the hit population in Albania during the 1996 outbreak. PMID- 11773145 TI - Chemoprevention of breast cancer: a model for change. PMID- 11773146 TI - Asking the obvious questions regarding patient burden. PMID- 11773147 TI - Irinotecan dosing: does the CPT in CPT-11 stand for "Can't Predict Toxicity"? PMID- 11773148 TI - Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost-effectiveness analysis. AB - PURPOSE: To estimate the effects on survival, quality-adjusted survival, and health care costs of using tamoxifen for primary prevention in subgroups of women at very high risk for breast cancer. PATIENTS AND METHODS: A decision analysis was performed using a hypothetical cohort of women that included subgroups with atypical hyperplasia, Gail risk greater than 5, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. Data sources were the Breast Cancer Prevention Trial, the Surveillance, Epidemiology, and End-Results program, time trade-off preference ratings, the Group Health Cooperative of Puget Sound, and the United States Health Care Financing Administration. RESULTS: Our model predicted that tamoxifen would prolong the average survival of cohort members initiating use at ages 35, 50, and 60 years by 70, 42, and 27 days, respectively. It would prolong survival even more for those in the higher-risk groups, especially those with atypical hyperplasia (202, 89, and 45 days). Tamoxifen use was also projected to extend quality-adjusted survival by 158, 80, and 50 days in the atypical hyperplasia group. For younger women in the highest risk groups, chemoprevention with tamoxifen was estimated to have cost savings or be cost effective, both with and without quality adjustments. CONCLUSION: Chemoprevention with tamoxifen may be particularly beneficial to women with atypical hyperplasia, 5-year Gail model risk greater than 5%, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. The benefits may be greater if tamoxifen is initiated before age 50 years rather than after and if the breast cancer risk reduction conferred by tamoxifen lasts longer than 5 years. For women with a very high risk of invasive breast cancer, chemoprevention with tamoxifen seems to be cost-effective. PMID- 11773149 TI - Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. AB - PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation. PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer. RESULTS: The median follow up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P <.0001) and increasing combined clinical stage (P <.0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P =.0048), increasing number of involved lymph nodes (P <.0001), and no use of tamoxifen (P =.0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P <.001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P =.008), and no use of tamoxifen (hazard ratio of 3.9, P =.027) independently predicted for LRR. CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease. PMID- 11773150 TI - Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients. AB - PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25 8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen. PMID- 11773151 TI - Phase II trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancer. AB - PURPOSE: To determine the efficacy of gemcitabine (GEM) plus vinorelbine (VRL) administered biweekly in pretreated patients with advanced breast cancer. PATIENTS AND METHODS: Advanced breast cancer patients without response, with stable disease, or with recurrence within 6 months of prior treatment were given GEM 1,000 mg/m(2) and VRL 25 mg/m(2), once every 2 weeks for at least six cycles. RESULTS: Of the 51 patients enrolled, 50 (median, age 58 years; range, 34 to 76 years) were assessable. All patients had prior chemotherapy with an anthracycline related regimen that included taxanes in 50% of the cases. Four patients (8%) had a complete response (CR) and 23 (46%) had a partial response (PR), for an overall response rate of 54%; 16 (32%) had stable disease and 7 (14%) experienced disease progression. Response occurred mainly in patients with soft tissue (83.3%) and lung metastasis (66.7%). Response duration was 4 to 8+, 4 to 9+, and 4 to 9 months for those with CR, PR, and stable disease, respectively. The regimen was well tolerated, with grade 1 to 2 myelotoxicity and asthenia reported. No patient required a dose reduction. Gastrointestinal side effects were negligible. Patients received 99.7% (range, 93.0% to 100.0%) of the planned dose-intensity of each drug. CONCLUSION: GEM in combination with VRL is an active regimen for advanced breast cancer patients, and biweekly administration significantly reduces myelotoxicity. PMID- 11773152 TI - Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. AB - PURPOSE: Insulin, a member of a family of growth factors that includes insulin like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer. PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained. RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P <.001), which, in turn, was associated with distant recurrence and death (P <.001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively. CONCLUSION: Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored. PMID- 11773153 TI - Survey of modalities of toxicity assessment and reporting in noncomparative prospective studies of chemotherapy in breast cancer. AB - PURPOSE: To review how toxicity, a main end point of phase II studies, is assessed and reported in published phase II chemotherapy trials in breast cancer. METHODS: A survey was performed by hand-searching studies published in seven distinguished journals between 1995 and 1999. All selected articles were independently evaluated by two investigators using an ad hoc study report form. Descriptive statistics, contingency tables, and the chi(2) test were applied. RESULTS: Overall, 122 articles were found; 65.6% lacked a statistical study design. Planned modalities for assessment of toxicity were inadequately reported in 20.5% of the studies. The scheduling of assessment of hematologic toxicity varied greatly. Toxicity was predominantly summarized per patient (69.7%). Although overall the World Health Organization scale was adopted more frequently (45.9%), the Common Toxicity Criteria (in different versions) were used more frequently in studies published in journals with a high impact factor (P =.001), in more recently initiated studies (P =.03), in sponsored studies (P =.0006), and in studies with an identifiable statistical design (P =.006). CONCLUSION: The wide diversity in modalities of toxicity assessment and reporting observed in this study suggests that the reliability of the body of published data on the toxicity of chemotherapy in breast cancer may be questionable. Current standards should be revised and harmonized to improve the reliability of such data. A checklist is proposed to help editorial evaluation of assessment and reporting of toxicity in phase II studies. PMID- 11773154 TI - Reinfusion of autologous lymphocytes with granulocyte-macrophage colony stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high dose chemotherapy for metastatic breast cancer. AB - PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune system is seriously compromised after HDCT, which precludes the development of effective immunotherapy. We investigated whether autologous lymphocytes, reinfused after HDCT, could induce a rapid recovery of T cells. PATIENTS AND METHODS: Three patients were monitored for immune recovery without reinfusion of lymphocytes. In the next 11 patients, stem cells were harvested after CT + granulocyte colony stimulating factor (G-CSF) and lymphocytes were harvested after CT + granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2. These patients received stem cells and G-CSF after the first HDCT; stem cells, G-CSF, and lymphocytes after the second; and stem cells, GM-CSF, and lymphocytes after the third HDCT. RESULTS: Patients not receiving lymphocyte reinfusion had a very slow recovery of lymphocytes. In particular, CD4 counts remained low (< 200/microL for 9 months). Lymphocyte reinfusion had a significant effect on the recovery of lymphocytes, T cells, and CD8+ T cells (normalized on day 25). Recovery of CD4+ T cells was significantly accelerated by lymphocyte reinfusion and GM-CSF, leading to counts of 500/microL at 25 days. CONCLUSION: Lymphocyte reinfusion with G-CSF had a significant effect on the recovery of CD8+ T cells, whereas rapid recovery of CD4+ T cells required lymphocyte reinfusion and GM-CSF, which possibly acts as a survival factor through activation of antigen presenting cells. Whether the rapid recovery of CD4+ and CD8+ T cells prevents or delays relapse of the disease should be further investigated. PMID- 11773155 TI - Patients' estimation of overall treatment burden: why not ask the obvious? AB - PURPOSE: We investigated the clinical validity of patients' estimation of overall treatment burden. This measure was expected to be responsive to the wide spectrum of reactions on treatment and thus less precise for specific effects. PATIENTS AND METHODS: After the first chemotherapy within a randomized, double-blind trial of the prophylaxis for delayed emesis (SAKK 90/95), 249 patients documented nausea and vomiting daily for 6 days. Over the whole period, they estimated nausea/vomiting (N/V) burden and overall treatment burden by linear analog-self assessment (LASA) indicators and documented other side effects. RESULTS: At day 6, the two burden indicators were moderately correlated (r = 0.58) in accordance with their different concepts. No, partial, or total control of delayed emesis (days 2 to 6) was reflected in a consistent pattern by both indicators, with a stronger and more significant effect (P <.001) on changes in N/V burden than overall treatment burden. In contrast, toxicity other than N/V, assessed independently by patients and physicians, was mainly associated with overall treatment burden. Patients who indicated at least one other side effect rated their overall burden substantially higher than those with no indication of other toxicity (P <.0001). Physician-rated toxicity had a similar effect (P <.0001). CONCLUSION: A direct patient estimation of overall treatment burden by a LASA indicator may serve as an end point in clinical trials, particularly when treatments with different toxicity profiles are being compared. It is complementary to physicians' ratings of specific toxicities and a major component of patient-rated symptom checklists and quality-of-life measures. PMID- 11773156 TI - Quality of life in long-term survivors of testicular cancer: a population-based case-control study. AB - PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer. PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added. RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P =.04) with decreased sexual enjoyment (P <.01), decreased desire (P =.02), and infertility (P <.01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P =.03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P =.002). Cases had greater difficulty in borrowing from banks (P <.001). CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life. PMID- 11773157 TI - Impact of body-size measures on irinotecan clearance: alternative dosing recommendations. AB - PURPOSE: To evaluate relationships between various body-size measures and irinotecan (CPT-11) clearance and metabolism in cancer patients, and to provide future dosing recommendations for this agent. PATIENTS AND METHODS: Pharmacokinetic data were obtained from 82 adult patients (50 men, 32 women; median age, 54 years) receiving CPT-11 as a 90-minute intravenous infusion (dose range, 175 to 350 mg/m(2)). In each patient, plasma samples were collected at timed intervals in the first administration of a 3-week schedule, and CPT-11 and its metabolite, SN-38, were measured by a liquid chromatographic assay. RESULTS: The mean (+/- SD) CPT-11 clearance was 33.6 +/- 10.8 L/h, with an interindividual variability (IIV) of 32.1%. When clearance was adjusted for body-surface area (BSA), the IIV was similar (34.0%). In addition, in a multiple linear regression analysis, none of the studied measures (BSA, lean body mass, [adjusted] ideal body weight, and body mass index) was a significant covariate (P >.13; r(2) <.014) in our population. Similarly, BSA did not significantly contribute to variability in the relative extent of conversion to SN-38 (P =.26). CONCLUSION: BSA is not a predictor of CPT-11 clearance or SN-38 pharmacokinetics and does not contribute to reducing kinetic variability. These findings provide a rationale for the conduct of a comparative phase III study between BSA-based dosing and flat or fixed dosing of CPT-11. PMID- 11773158 TI - Phase I study of combination topotecan and carboplatin in pediatric solid tumors. AB - PURPOSE: We conducted a phase I trial of escalating doses of topotecan (TOPO) in association with a fixed systemic exposure of carboplatin (CARBO) with or without granulocyte colony-stimulating factor (G-CSF) in children. PATIENTS AND METHODS: Two separate cohorts of patients (pts) with solid tumors were studied: (A) pts with refractory or recurrent disease and (B) pts with no prior myelosuppressive therapy or newly diagnosed tumors for which there was no standard chemotherapy. CARBO was given on day 1 at an area under the curve of 6.5, followed by TOPO as a continuous infusion for 3 days; the starting dose of TOPO was 0.50 mg/m(2)/d. Cycles were repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d starting on day 4. RESULTS: Forty-eight of 51 pts were assessable for toxicity. In group A, dose-limiting myelosuppression persisted despite de-escalation of TOPO to 0.3 mg/m(2)/d and use of G-CSF. In group B, the maximum-tolerated dose of TOPO was 0.5 mg/m(2)/d for 3 days, and 0.6 mg/m(2)/d for 3 days with G-CSF. No significant nonhematologic toxicities were observed. Among 46 pts assessable for response, one had complete response, five had partial response, and 18 had stable disease. CONCLUSION: Although this combination possesses antineoplastic activity in pediatric solid tumors, hematologic toxicity precluded any meaningful TOPO dose escalation. The addition of G-CSF did not alter this. The potential for preservation of activity and diminution of toxicity with alternative sequences and schedules of administration (topoisomerase followed by alkylating or platinating agents) should be evaluated. PMID- 11773159 TI - Troxacitabine, an L-stereoisomeric nucleoside analog, on a five-times-daily schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies. AB - PURPOSE: To assess the feasibility of administering troxacitabine, a unique L nucleoside that is not a substrate for deoxycytidine deaminase-mediated catabolism, as a 30-minute intravenous (IV) infusion daily for 5 days. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of troxacitabine as a 30-minute IV infusion daily for 5 days. Plasma and urine sampling was performed to characterize the pharmacokinetics and pharmacodynamics of troxacitabine. RESULTS: Thirty-nine patients received 124 courses of troxacitabine at eight dose levels ranging from 0.12 to 1.8 mg/m(2)/d. Severe neutropenia that was protracted (> 5 days) and/or associated with fever, and skin rashes were consistently experienced by heavily (HP) and minimally pretreated (MP) patients at doses exceeding 1.2 and 1.5 mg/m(2)/d, respectively. At troxacitabine doses > or = 1.2 mg/m(2)/d, treatment was often delayed 1 additional week for complete resolution of hematologic effects, resulting in lengthening of the treatment interval from every 3 to 4 weeks. Skin rash, palmar plantar erythrodysesthesia, and thrombocytopenia were also observed and were occasionally severe, particularly at the highest doses. A patient with metastatic ocular melanoma experienced a partial response. Pharmacokinetics of troxacitabine were dose-independent; mean (SD) values for the volume of distribution at steady state and clearance (Cl(s)) were 60 (32) L and 161 (33) mL/min, respectively, on day 1. After treatment on the fifth day, terminal half-life values averaged 39 (63) hours, and Cl(s) was reduced by approximately 20%, averaging 127 (27) mL/min. The principal mode of drug elimination was renal. CONCLUSION: Recommended doses for phase II studies of troxacitabine as a 30-minute infusion daily for 5 days every 4 weeks are 1.5 and 1.2 mg/m(2)/d for MP and HP patients, respectively. Broad disease-directed evaluations of troxacitabine on this schedule and possibly less frequent schedules are warranted. PMID- 11773160 TI - Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. AB - PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical trials. PATIENTS AND METHODS: We studied 104 pre- and/or on-ZD1839 therapy ( approximately at day 28 of therapy) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839. We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated (phosphorylated) EGFR. Effects on receptor signaling (activated mitogen-activated protein kinase [MAPK]), proliferation, p27(KIP1), and maturation were also assessed. RESULTS: Histopathologically, the stratum corneum of the epidermis was thinner during therapy (P <.001). In hair follicles, prominent keratin plugs and microorganisms were found in dilated infundibula. ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells (P <.001). In addition, ZD1839 inhibited MAPK activation (P <.001) and reduced keratinocyte proliferation index (P <.001). Concomitantly, ZD1839 increased the expression of p27(KIP1) (P <.001) and maturation markers (P <.001) and increased apoptosis (P <.001). These effects were observed at all dose levels, before reaching dose-limiting toxicities. CONCLUSION: ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo. These effects were profound at doses well below the one producing unacceptable toxicity, a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials. PMID- 11773161 TI - Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma. AB - PURPOSE: Reactive oxidative species (ROS) produced by phagocytic cells have been ascribed a role in the localized suppression of lymphocyte function within malignant tumors. Histamine has been shown to inhibit ROS formation and possibly synergize with cytokines to permit activation of natural killer cells and T cells. This study was designed to determine whether the addition of histamine to a subcutaneous (SC) regimen of interleukin-2 (IL-2) would improve the survival of metastatic melanoma patients. PATIENTS AND METHODS: A phase III, multicenter, randomized, parallel group study comparing IL-2 plus histamine with IL-2 alone was conducted in 305 patients with advanced metastatic melanoma. Patients were randomized to IL-2 (9 MIU/m(2) bid SC on days 1 to 2 of weeks 1 and 3, and 2 MIU/m(2) bid SC on days 1 to 5 of weeks 2 and 4) with or without histamine (1.0 mg bid SC days 1 to 5, weeks 1 to 4). The primary end point, survival, was prospectively applied to all randomized patients (intent-to-treat-overall population, ITT-OA) and all patients having liver metastases at randomization (ITT-LM population). Secondary end points included safety of the combined treatment, time to disease progression, and response rate. RESULTS: Combined treatment with histamine plus IL-2 significantly improved overall survival in the ITT-LM population (P =.004) and showed a trend for improved survival in the ITT population (P =.125). Grade 3 and 4 adverse events were comparable in the two arms. CONCLUSION: Use of histamine as an adjunct to IL-2 is safe, well tolerated, and associated with a statistically significant prolongation of survival compared with IL-2 alone in metastatic melanoma patients with liver involvement. Further trials to confirm and understand the role of histamine in this combination treatment are underway. PMID- 11773162 TI - Melanoma information on the Internet: often incomplete--a public health opportunity? AB - PURPOSE: To assess the accuracy and completeness of information regarding melanoma on the Internet, retrieved by use of search engines. METHODS: The first 30 uniform/universal resource locators (URLs) from each of eight search engines using the search term "melanoma" were retrieved for evaluation of accuracy and completeness using a 35-point checklist rating system instrument. Four reviewers independently rated each of 35 sites, and one reviewer rated all 74 assessable sites. Kappa statistics were used to evaluate interrater variability. RESULTS: A total of 74 assessable Web sites were evaluated. The remainder were inaccessible, link pages only, or duplicates. Thirty-five Web sites were each independently rated by four reviewers. The remaining 39 Web sites were each rated by one reviewer. The mean kappa statistic for all variables and all rater pairs for which a kappa could be calculated was 0.824, indicating excellent overall inter rater reliability. The majority of Web sites failed to include complete information on general information, risk factors, diagnosis, treatment, prevention, and prognosis. Ten Web sites (14%) contained a total of 13 inaccuracies, most relatively minor. CONCLUSION: Medical information retrieved with the search term melanoma was likely to lack complete basic melanoma information and contained inaccuracies in 14% of sites. Health care providers can help patients by recommending comprehensive and accurate Web sites for patient review, by working to create accurate and thorough Web-based health information material, and by educating patients and the public about the variability in completeness and accuracy. PMID- 11773163 TI - Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. AB - PURPOSE: A strain of Salmonella typhimurium (VNP20009), attenuated by chromosomal deletion of the purI and msbB genes, was found to target to tumor and inhibit tumor growth in mice. These findings led to the present phase I study of the intravenous infusion of VNP20009 to patients with metastatic cancer. PATIENTS AND METHODS: In cohorts consisting of three to six patients, 24 patients with metastatic melanoma and one patient with metastatic renal cell carcinoma received 30-minute intravenous bolus infusions containing 10(6) to 10(9) cfu/m(2) of VNP20009. Patients were evaluated for dose-related toxicities, selective replication within tumors, and antitumor effects. RESULTS: The maximum-tolerated dose was 3 x 10(8) cfu/m(2). Dose-limiting toxicity was observed in patients receiving 1 x 10(9) cfu/m(2), which included thrombocytopenia, anemia, persistent bacteremia, hyperbilirubinemia, diarrhea, vomiting, nausea, elevated alkaline phosphatase, and hypophosphatemia. VNP20009 induced a dose-related increase in the circulation of proinflammatory cytokines, such as interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, and IL-12. Focal tumor colonization was observed in two patients receiving 1 x 10(9) cfu/m(2) and in one patient receiving 3 x 10(8) cfu/m(2). None of the patients experienced objective tumor regression, including those patients with colonized tumors. CONCLUSION: The VNP20009 strain of Salmonella typhimurium can be safely administered to patients, and at the highest tolerated dose, some tumor colonization was observed. No antitumor effects were seen, and additional studies are required to reduce dose related toxicity and improve tumor localization. PMID- 11773164 TI - Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. AB - PURPOSE: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are overexpressed in Kaposi's sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. RESULTS: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m(2)/d. Prior KS therapy was reported by 17 patients (94%). COL-3-related grade 3 or 4 adverse events were reported by six patients and included photosensitivity, rash, and headache. There was one complete response and seven partial responses, for an overall response rate of 44%, with a median response duration of 25+ weeks. The median COL-3 half-life was 39.3 hours (range, 4.1 to 251.1 hours). There was a significant difference between responders and nonresponders with respect to the change in MMP-2 serum levels from baseline to minimum value on treatment (P =.037). CONCLUSION: COL-3 administered orally once daily to patients with AIDS-related KS is reasonably well tolerated. The most common adverse event was dose-related photosensitivity. Antitumor activity was noted. Further evaluation of COL-3 for the treatment of KS is warranted. PMID- 11773165 TI - Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. AB - PURPOSE: To determine the safety and efficacy of capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) in patients with metastatic or unresectable, locally advanced pancreatic cancer. PATIENTS AND METHODS: Forty-two patients were treated with oral capecitabine 1,250 mg/m(2) administered twice daily (2,500 mg/m(2)/d) as intermittent therapy in 3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment. Tumor lesions were assessed by computed tomography scan or physical examination at 6-week intervals (after every two cycles). Adverse events were monitored continuously during treatment and for 28 days after the last dose of study drug. RESULTS: Ten (24%) of 42 patients experienced a clinical benefit response (95% confidence interval [CI], 12.1% to 39.5%) as evidenced by improvement in pain intensity, analgesic consumption, and/or Karnofsky performance status. Three (7.3%) of the 41 patients with measurable disease had an objective response (partial). The median time to objective response was 85 days (range, 47 to 91 days) and duration of response was 208, 260, and 566 days for the three responding patients. One patient with nonmeasurable but assessable disease had improved residual disease with a positive clinical benefit response, for a total of four responses among the 42 assessable patients, for an overall response rate of 9.5% (90% CI, 3.3% to 20.5%). Capecitabine was generally well tolerated. CONCLUSION: Treatment with capecitabine resulted in clinically significant beneficial effects on tumor related symptoms and yielded objective response activity in patients with metastatic or locally advanced pancreatic cancer. These results together with its generally tolerable safety profile and the added advantage of oral administration provide the basis for further evaluating capecitabine as a single agent or in combination with other treatment modalities in this patient population. PMID- 11773167 TI - Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. AB - PURPOSE: Since 1986, the recommended therapy for patients with ovarian cancer has included surgery and chemotherapy with a platinum compound (cisplatin or carboplatin). The purpose of this study is to assess the use of chemotherapy in elderly patients with advanced ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database represents approximately 14% of the United States population and provides clinical and demographic information on cancer patients covered by Medicare, along with health care-utilization data from Medicare claims files. We analyzed the association of demographic and clinical factors with treatment among patients diagnosed from 1992 to 1996 with stage III or IV ovarian cancer, who survived > or = 120 days beyond diagnosis, and were > or = 65 years of age (N = 1,775). RESULTS: Approximately 83% of elderly patients received some form of chemotherapy within 4 months of diagnosis. In a multiple logistic regression model with patients aged 65 to 69 years as the reference, the odds ratios of receiving chemotherapy were 0.96 (95% confidence interval [CI], 0.63 to 1.46) for ages 70 to 74, 0.65 (95% CI, 0.43 to 1.00) for 75 to 79, 0.24 (95% CI, 0.15 to 0.37) for 80 to 84, and 0.12 (95% CI, 0.07 to 0.19) for 85+. Hispanic patients were less likely to receive chemotherapy than non-Hispanic white patients. Since 1992, paclitaxel has gradually replaced cyclophosphamide as the drug most commonly used with platinum. CONCLUSION: Despite its proven efficacy in treating ovarian cancer, chemotherapy seems to be used less among patients over age 65, especially those who are nonwhite and/or in the oldest age groups. Further research is needed to elucidate to what degree this represents appropriate clinical judgment and to what degree other factors, such as patient choice, play a role. PMID- 11773166 TI - Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer. AB - PURPOSE: Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs act synergistically, a randomized phase II study was initiated to investigate the therapeutic potential and tolerance of this combination in the front-line setting. PATIENTS AND METHODS: Ninety-two patients with previously untreated, measurable disease were randomized to receive biweekly oxaliplatin 85 mg/m(2) plus irinotecan 175 mg/m(2) or raltitrexed 3 mg/m(2) given on day 1 every 3 weeks. Upon development of progressive disease, second-line treatment with the opposite arm was effected. RESULTS: Patients allocated to oxaliplatin/irinotecan had a significantly better radiologically confirmed response rate (43.5% v 19.6%; P =.0025) and longer progression-free survival (median, 7.1 v 5.0 months; P =.0033). Improvement in overall survival, however, did not reach the level of significance (median, 16.0 v 16.5 months; P =.3943). The response rate after cross-over was 33.3% (eight of 24) for assessable patients treated with oxaliplatin/irinotecan compared with 14.2% (three of 21) for those treated with second-line raltitrexed. Oxaliplatin/irinotecan caused more hematologic and gastrointestinal toxicities, necessitating dose reductions in 10 of the first 20 patients. After adjustment of the irinotecan starting dose from 175 to 150 mg/m(2), tolerance of treatment was acceptable; the most commonly encountered events (all grades) were neutropenia (81%), alopecia (65%), nausea/emesis (62%), peripheral sensory neuropathy (62%), and diarrhea (46%). CONCLUSION: Oxaliplatin/irinotecan seems beneficial as first-line therapy in advanced colorectal cancer, with an acceptable toxicity profile at the reduced irinotecan dose level. Its promising therapeutic potential is supported by the high response activity noted in the raltitrexed control arm after cross-over, which may also explain the lack of a difference in overall survival. PMID- 11773168 TI - Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. AB - PURPOSE: Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity. PATIENTS AND METHODS: Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B). RESULTS: Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P =.007 and P =.02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P =.005 andP =.02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P =.36 and P =.29), respectively. Treatment had a significant impact on OS and PFS. CONCLUSION: Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT. PMID- 11773169 TI - High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. AB - PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of (153)Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer. PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of (153)Sm-EDTMP. RESULTS: Thirty patients were treated with (153)Sm EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of (153)Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after (153)Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after (153)Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 x 10(6) CD34(+)/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status. CONCLUSION: (153)Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi (153)Sm-EDTMP/kg requires PBPC grafts with more than 2 x 10(6) CD34(+)/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal. PMID- 11773170 TI - Brief chemotherapy and involved-region irradiation for limited-stage diffuse large-cell lymphoma: an 18-year experience from the British Columbia Cancer Agency. AB - PURPOSE: To evaluate clinical outcome of patients with limited-stage diffuse large-cell lymphoma (DLCL) treated with three cycles of chemotherapy followed by involved-region irradiation (IRRT). PATIENTS AND METHODS: Adults with limited stage DLCL were treated with brief doxorubicin-containing chemotherapy regimens between 1980 and 1998. IRRT was administered 3 to 4 weeks after the third chemotherapy treatment in a dose equivalent to 30 Gy in 10 fractions. RESULTS: Three hundred and eight patients (median age, 64 years) were included, and 299 experienced complete remission. After a median follow-up of 86 months, 64 patients developed progressive disease, and 104 patients died (43 from lymphoma, three from toxicity, and 58 from other causes). Actuarial overall and progression free survival (PFS) rates were, respectively, 80% and 81% at 5 years and 63% and 74% at 10 years. For subgroups identified using the Miller modification of the International Prognostic Index (IPI), the overall survival rates at 5 and 10 years were, respectively, 97% and 89% (no factors), 77% and 56% (one or two factors), and 58% and 48% (three or four factors), and the 5-year and 10-year PFS rates were, respectively, 94% and 89% (no factors), 79% and 73% (one or two factors), and 60% and 50% (three or four factors). Men with testicular presentation, had a definitely inferior outcome. CONCLUSION: Long-term outcome with three cycles of doxorubicin-based chemotherapy and IRRT confirms that this is a successful approach for the majority of patients with limited-stage DLCL. Subgroups with worse prognoses can be identified, and these patients should be offered alternative treatment approaches. PMID- 11773171 TI - Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. AB - PURPOSE: We conducted a retrospective analysis to evaluate the safety and efficacy of Campath-1H, an anti-CD52 humanized monoclonal antibody, in previously treated T-prolymphocytic leukemia (T-PLL) patients in a compassionate-use program. PATIENTS AND METHODS: Seventy-six patients with T-PLL (including four chemotherapy-naive patients) received 3, 10, and 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly, as 2-hour intravenous infusions, for 4 to 12 weeks. RESULTS: Median patient age was 60 years (range, 35 to 84). Spleen liver, lymph node, and skin involvement were present in 64%, 40%, 54%, and 18% of patients, respectively. All tested patients had CD2, CD7, CD4, and/or CD8 positivity, whereas CD5 and CD3 were positive in 98% and 96% of tested patients, respectively. The objective response rate was 51% (95% confidence interval [CI], 40% to 63%), with a 39.5% complete response (CR) rate (95% CI, 28% to 51%). The median duration of CR was 8.7 months (range, 0.13+ to 44.4), and median time to progression was 4.5 months (range, 0.1 to 45.4) compared with 2.3 months (range, 0.2 to 28.1) after first-line chemotherapy. The median overall survival was 7.5 months (14.8 months for CR patients). The most common Campath-1H related adverse events were acute reactions during or immediately after infusions. Fifteen infectious episodes occurred during treatment in 10 patients (13%), leading to treatment discontinuation in three. Eight patients experienced possibly related, late-onset infections. Severe thrombocytopenia and/or neutropenia occurred in six patients (8%), leading to treatment discontinuation in four. Two treatment-related deaths occurred. CONCLUSION: Campath-1H is an active drug in T-PLL patients for whom first-line therapy has failed. It has a favorable risk/benefit ratio and should be prospectively investigated in chemotherapy-naive patients. PMID- 11773172 TI - Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. AB - PURPOSE: A small proportion of patients with chronic myeloid leukemia (CML) achieve a complete cytogenetic response (CCR), defined as the disappearance of Philadelphia (Ph) chromosome-positive metaphases, after treatment with interferon alfa (IFN). In this population of patients, the question of whether treatment should then be withdrawn is not yet resolved. PATIENTS AND METHODS: In the present study, we followed 15 patients who stopped IFN after achieving CCR. In nine patients IFN was stopped in view of adverse reactions (n = 8) or patient's choice (n = 1). For the remaining six patients, the treatment was stopped because no BCR/ABL rearrangement could be detected by reverse transcriptase polymerase chain reaction (RT-PCR) in four successive analyses using peripheral-blood samples. RESULTS: Loss of CCR and survival were not statistically different (P =.48; P =.7) for the 15 patients who stopped IFN compared with 41 other CCR patients who continued IFN therapy in our institution. The median follow-up after discontinuation of IFN treatment was 36 months (range, 6 to 108 months). Seven patients (47%) (females, or CCR > 24 months and RT-PCR negative before IFN cessation; P <.0001) did not relapse. Eight other patients (53%) relapsed (lost CCR) within 3 to 33 months of treatment discontinuation. One of them relapsed in major cytogenetic remission (MCR) and was still in MCR 87 months after stopping therapy without any treatment. CONCLUSION: It is possible to stop IFN treatment at least in some patients with CML who achieve a prolonged period of CCR. This study also illustrates the hypothesis that persistence of low numbers of Ph positive cells does not necessarily imply hematologic relapse. PMID- 11773173 TI - New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group. AB - PURPOSE: To evaluate salvage treatment outcome of patients with relapsed Hodgkin's disease (HD) and to distinguish different risk groups using identified prognostic factors. PATIENTS AND METHODS: From 4,754 patients registered in the German Hodgkin's Lymphoma Study Group (GHSG) database between 1988 and 1999, 422 patients with early (n = 170) or late (n = 252) relapsed HD were identified. One hundred seven patients (25%) relapsed after radiotherapy (RT) for early stages, 133 patients (32%) after combined-modality therapy for intermediate stages, and 182 patients (43%) after chemotherapy (CT) and RT to initial bulky disease or residual lymphoma for advanced stages. At relapse, characteristics of these 422 patients (median age, 38 years; range, 17 to 77) were stage III/IV, 45%; B symptoms, 24%; elevated erythrocyte sedimentation rate, 29%; anemia, 13%; and Karnofsky performance score, less than 90 in 13%. At first relapse, salvage treatment was RT in 13%, CT in 54%, and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) in 33%. RESULTS: Median follow-up time after relapse was 45 months. Freedom from second failure (FF2F) and overall survival (OS) were 81% and 89% for relapse after RT, 33% and 46% for early relapse after CT, and 43% and 71% for late relapse after CT, respectively. In multivariate analysis, independent risk factors were time to relapse, clinical stage at relapse, and anemia at relapse. Four subgroups with significantly different FF2F and OS were identified. The prognostic score was predictive for patients who relapsed after RT, CT with conventional CT salvage, and CT with HDCT/ASCT. CONCLUSION: In the GHSG database, time to relapse and clinical stage and anemia at relapse are relevant factors and can be used to form a prognostic score for HD patients at relapse. PMID- 11773174 TI - Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments. AB - PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS. PMID- 11773175 TI - Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber ALL Consortium Protocol 87-01. AB - PURPOSE: To improve efficacy and reduce toxicity of treatment for children with acute lymphoblastic leukemia. PATIENTS AND METHODS: Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated). RESULTS: At a median follow-up of 9.2 years, the 9-year event-free survival (EFS +/- SE) was 75% +/- 2% for all 369 patients, 77% +/- 4% for the 142 SR patients, and 73% +/- 3% for the 227 HR/VHR patients (P =.37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% +/- 2% for the entire population, 93% +/- 2% for SR children, and 79% +/- 3% for HR and VHR children (P <.01 comparing SR and HR/VHR). CONCLUSION: A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem. PMID- 11773176 TI - Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. AB - PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease. PMID- 11773177 TI - Cooperative role of telomerase activity and p16 expression in the prognosis of non-small-cell lung cancer. AB - PURPOSE: Telomerase activity and p16 expression can be considered two of the most important molecular markers implicated in tumorigenesis. Our main aim was to study the cooperative role of both molecular alterations in the prognosis of patients surgically resected for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We have determined telomerase activity and p16 expression in a series of 98 prospectively collected NSCLC specimens obtained from patients who had undergone surgery without other treatment. Telomerase activity was investigated by a telomeric repeat amplification protocol enzyme-linked immunosorbent assay based procedure, and p16 expression was examined by Western blot. Associations with survival were evaluated. RESULTS: Positive results for telomerase activity were found in 82% of the cases, and this variable correlated with poor differentiation and recurrence of tumors. Lack of p16 expression was observed in 61% of tumors, and a significant association with tumor recurrence was also observed. By univariate analysis, both negative telomerase activity and p16 positive expression were significantly correlated with a better prognosis. Moreover, statistics for equality of survival distributions for telomerase, adjusted for p16, indicated a positive interaction between both parameters. For telomerase-positive tumors, p16 expression emerged as a significant independent protective variable, as indicated by Cox multivariate analysis (relative risk [RR], 0.214; P =.014). This protective effect was maintained only for stage I and II tumors (RR, 0.108; P =.046). CONCLUSION: These results suggest that the combined telomerase activity and p16 expression analyses may be of prognostic importance in NSCLC, especially for patients affected by stage I and II tumors. PMID- 11773178 TI - Outcomes and cost-effectiveness of alternative staging strategies for non-small cell lung cancer. AB - PURPOSE: To identify the optimal strategy for staging the mediastinum of patients with known non-small-cell lung cancer (NSCLC), stratified by tumor (T) classification. METHODS: We used a decision-analytic model to compare the health outcomes and cost-effectiveness of three staging strategies: (1) chest computed tomography alone, (2) selective mediastinoscopy, and (3) routine mediastinoscopy. The overall effectiveness and cost of each strategy was a function of the proportion of patients accurately staged and the risks, benefits, and costs of the diagnostic tests and treatments used. Probability estimates and costs were derived from primary data and the literature. We adopted a societal perspective and calculated incremental cost-effectiveness ratios (ICERs) as cost per quality adjusted life year (QALY) gained. RESULTS: Both mediastinoscopy strategies correctly identified more patients with mediastinal involvement (N2/N3 disease) and assigned them to multimodal regimens. Routine mediastinoscopy maximized quality-adjusted life expectancy in all patients, irrespective of T classification, and this result was robust to varying the model estimates over their reported ranges. In T1 patients, selective mediastinoscopy cost $24,500 per QALY gained, compared with $78,800 per QALY gained for routine mediastinoscopy. In T2 and T3 patients, the ICER of routine mediastinoscopy was more favorable ($42,800 and $53,400 per QALY gained, respectively). CONCLUSION: Routine mediastinoscopy maximizes quality-adjusted life expectancy in patients with known NSCLC, and its ICER compares favorably with other currently accepted medical technologies. The survival benefit and cost-effectiveness of this strategy are greater in patients with T2 and T3 tumors and are likely to improve with advances in multimodal therapy. PMID- 11773179 TI - Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. AB - PURPOSE: A multicenter phase II trial of ranpirnase (Onconase; Alfacell Corp, Bloomfield, NJ) as a single agent was conducted to further assess the safety and clinical efficacy of this novel antitumor ribonuclease. Patients with unresectable and histologically confirmed malignant mesothelioma (MM) were eligible. PATIENTS AND METHODS: One hundred five patients with Eastern Cooperative Oncology Group performance status 0 to 2 were enrolled onto the study. Thirty-seven percent of patients had not responded to prior chemotherapy. The primary end point of the study was survival. Tumor responses and time to progression were also assessed. The Cancer and Leukemia Group B (CALGB) prognostic group criteria were used to define a treatment target group (TTG). Both the intent-to-treat (ITT) and the TTG populations were analyzed for survival. RESULTS: Median survival times of 6 months for the ITT and 8.3 months for the TTG populations were observed. The 1- and 2-year survival rates were 34.3% and 21.6% for ITT, respectively, and 42% and 26.8% for TTG, respectively. Among the 81 patients assessable for tumor response, four had partial responses, two had minor regressions, and thirty-five experienced stabilization of previously progressive disease. Patients with responses and stable disease demonstrated markedly prolonged survival. Ranpirnase was well tolerated in the majority of patients, and there were no drug-related deaths. CONCLUSION: Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed. PMID- 11773180 TI - Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. AB - PURPOSE: To estimate the risk of ischemic stroke in patients irradiated for head and neck tumors. PATIENTS AND METHODS: The incidence of ischemic stroke was determined in 367 patients with head and neck tumors (162 larynx carcinomas, 114 pleomorphic adenomas, and 91 parotid carcinomas) who had been treated with local radiotherapy (RT) at an age younger than 60 years. Relative risk (RR) of ischemic stroke was determined by comparison with population rates from a stroke-incidence register, adjusted for sex and age. Other risk factors for stroke (hypertension, smoking, hypercholesterolemia, diabetes mellitus [DM]) were registered. The median follow-up time after RT was 7.7 years (3,011 person-years of follow-up). RESULTS: Fourteen cases of stroke occurred (expected, 2.5; RR, 5.6; 95% confidence interval [CI], 3.1 to 9.4): eight in patients with laryngeal carcinoma (expected,1.56; RR, 5.1; 95% CI, 2.2 to 10.1), four in pleomorphic adenoma patients (expected, 0.71; RR, 5.7; 95% CI, 1.5 to 14.5), and two in parotid carcinoma patients (expected, 0.24; RR, 8.5, 95% CI, 1.0 to 30.6). Five of six strokes in patients irradiated for a parotid tumor occurred at the ipsilateral side. Analysis of other risk factors for cerebrovascular disease showed hypertension and DM to cause an increase of the RR after RT. After more than 10 years' follow-up, the RR was 10.1 (95% CI, 4.4 to 20.0). The 15-year cumulative risk of stroke after RT on the neck was 12.0% (95% CI, 6.5% to 21.4%). CONCLUSION: This is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patients. PMID- 11773181 TI - Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. AB - PURPOSE: To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma (RCC) treated with interferon-alfa as initial systemic therapy. The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy. PATIENTS AND METHODS: Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospective clinical trials were the subjects of this retrospective analysis. Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model. RESULTS: The median overall survival time was 13 months. The median time to progression was 4.7 months. Five variables were used as risk factors for short survival: low Karnofsky performance status, high lactate dehydrogenase, low serum hemoglobin, high corrected serum calcium, and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year. Each patient was assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). The median time to death of patients deemed favorable risk was 30 months. Median survival time in the intermediate-risk group was 14 months. In contrast, the poor-risk group had a median survival time of 5 months. CONCLUSION: Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm. PMID- 11773182 TI - Salvage chemotherapy for patients with advanced pure seminoma. AB - PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment. PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem cell rescue. RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease. CONCLUSION: Most patients with advanced seminoma are cured with standard first line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease. PMID- 11773183 TI - Phase II trial of thalidomide for patients with advanced renal cell carcinoma. AB - PURPOSE: To assess efficacy and toxicity of thalidomide in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-six patients with RCC were treated with thalidomide at a starting dose of 200 mg daily. Thalidomide was increased by 200 mg every 2 weeks until a maximum dose of 800 mg or prohibitive toxicity was reached. Fifteen patients had prior nephrectomy, 11 patients had no prior systemic therapy, and 15 had received one prior systemic regimen. RESULTS: A maximum dose of 800 mg, 600 mg, 400 mg, and 200 mg was reached in five, 10, eight, and three patients, respectively. Grade 2 and 3 dyspnea occurred in four and three patients, respectively. Grade 2 and 3 neurologic toxicity was observed in five and two patients, respectively. Of the 25 assessable patients, the best response was stable disease in 16 (95% confidence interval [CI], 43% to 82%) patients. The 6-month progression-free survival rate was 32% (95% CI, 14% to 50%). Three patients achieved prolonged stable disease of 16, 16+, and 18+ months, including two patients who were refractory to previous cytokine therapy. Fifty-seven percent were alive at 1 year (95% CI, 37% to 76%). CONCLUSION: This trial does not support the routine use of thalidomide to induce partial response for metastatic RCC. Because disease stabilization occurs as a part of the natural history of metastatic RCC, the potential effect of thalidomide on progression free and overall survival for patients with advanced RCC is being addressed in a randomized phase III trial. New immunomodulatory analogs of thalidomide that have shown potentially greater antitumor effects in preclinical models warrant study in metastatic RCC. PMID- 11773184 TI - Costs of treatment for elderly women with early-stage breast cancer in fee-for service settings. AB - PURPOSE: This study provides population-based estimates of the treatment costs for elderly women with early-stage breast cancer, with emphasis on costs of modified radical mastectomy (MRM) compared with breast-conserving surgery (BCS) and radiation therapy (RT). PATIENTS AND METHODS: Women with breast cancer from the Surveillance, Epidemiology, and End Results cancer registries were linked with their Medicare claims, 1990 through 1998. Each claim was assigned to an initial, continuing, or terminal care phase after a cancer diagnosis. Mean monthly phase-specific costs were determined for all health care and for treatment related only to cancer. Cumulative long-term costs of care that accrue during a women's remaining lifetime were calculated by treatment group. RESULTS: Initial care costs for the 6 months after diagnosis for women who underwent BCS with RT were approximately $450 per month higher than for women with MRM. During the continuing-care phase, costs for women undergoing BCS with RT were significantly less expensive than for MRM cases. The two groups had similar costs in the terminal-care phase. Assuming the same survival distributions, long-term costs for women undergoing BCS with RT were not statistically different than for women undergoing MRM. CONCLUSION: Although mastectomy was less costly in the initial phase, the lifetime costs of BCS with RT and mastectomy were equivalent. Thus, women's preferences, resources to cover out-of-pocket costs, and life situations should be the major factors addressed in shared decision making about treatment options. PMID- 11773185 TI - Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the cardiovascular thrombolytic to open occluded lines trial. AB - PURPOSE: To evaluate the safety and efficacy of alteplase (TPA) for restoring function to occluded central venous catheters (CVCs). PATIENTS AND METHODS: The study design was a phase III, open-label, single-arm multicenter trial. Subjects with occluded, nondialysis CVCs were enrolled. All subjects received a 2-mg dose of TPA within the dysfunctional catheter lumen that was allowed to dwell for 30 to 120 minutes. Functionality was tested at 30 and 120 minutes. If the CVC remained obstructed at 120 minutes, a second 2-mg TPA dose was allowed to dwell for 30 to 120 minutes. The primary safety end point was the rate of intracranial hemorrhage (ICH) within 5 days of treatment, and serious adverse events were recorded up to 30 days. RESULTS: Nine hundred ninety-five patients received treatment (female, 562; male, 433; mean age, 50.7 years; range, 2 to 91 years). CVCs treated were as follows: single (26%), double (39%), or triple (6%) lumen catheters or ports (29%). The primary end point was 0% ICH within 5 days. There were no cases of death, major bleeding episodes, or embolic events attributable to treatment. Flow was successfully restored in 52% and 78% of CVCs at 30 and 120 minutes after one dose, and 84% and 87% at 30 and 120 minutes after a second dose, respectively. Restoration of flow was 86%, 93%, 90%, and 79%, for single, double, and triple lumen catheters and ports, respectively. Estimated 30-day catheter patency was 74%. CONCLUSION: A regimen of up to two 2-mg doses of TPA is safe and effective for the restoration of flow to occluded central venous catheters. PMID- 11773186 TI - STI571: a paradigm of new agents for cancer therapeutics. AB - STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose selection, optimizing therapy, and predicting response, as are possible mechanisms of resistance to STI571. Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies are explored. PMID- 11773187 TI - Palliative uses of methylphenidate in patients with cancer: a review. AB - PURPOSE: Cancer is, unfortunately, often a terminal disease. The goal of therapy for many patients with cancer is palliation of symptoms common at the end of life, including pain, depression, and cognitive dysfunction. Methylphenidate is a psychostimulant most commonly used in the treatment of attention deficit hyperactivity disorder. In this report, we review the use of methylphenidate in the palliative care of patients with cancer. METHODS: This review was written on the basis of a computerized literature search of Medline. We considered all English language publications from 1966 to present using the following key words: methylphenidate, palliative care, and cancer. Forty-nine articles were identified as being relevant for this review. RESULTS: On the basis of this review, we came to the conclusion that methylphenidate is used to ameliorate opioid-induced somnolence, to augment the analgesic effects of opioids, to treat depression, and to improve cognitive function in patients with cancer. CONCLUSION: The medical literature supports the palliative use of methylphenidate in the care of patients with cancer. Further placebo-controlled trials are needed to elucidate the precise role that methylphenidate will have in providing symptom relief to dying patients. PMID- 11773188 TI - Extramedullary sites of involvement in hematologic malignancies: case 1. Multifocal intracranial involvement with mantle-cell lymphoma. PMID- 11773189 TI - Extramedullary sites of involvement in hematologic malignancies: case 2. Lymphocyte morphology in splenic marginal zone lymphoma. PMID- 11773190 TI - Extramedullary sites of involvement in hematologic malignancies: case 3. Hemorrhagic gastric plasmacytoma as the primary presentation in multiple myeloma. PMID- 11773191 TI - Opioid rotation in the management of refractory cancer pain. PMID- 11773195 TI - Replacement of carboplatin by oxaliplatin may be one solution for patients treated for ovarian carcinoma who are hypersensitive to carboplatin. PMID- 11773196 TI - Human bone marrow myeloma cells express RANKL. PMID- 11773197 TI - Tumor lysis syndrome after STI571 in Philadelphia chromosome-positive acute lymphoblastic leukemia. PMID- 11773198 TI - Radiation recall dermatitis from high-dose interferon alfa-2b. PMID- 11773199 TI - Treatment of intracranial metastatic esthesioneuroblastoma. PMID- 11773200 TI - Coordinated genetic control of neoplastic and nonneoplastic diseases in mice. AB - Some models of aging imply that late-life diseases, though roughly synchronous, are the result of distinct pathophysiological processes, each in turn influenced by polymorphisms at multiple loci. Other models suggest that the dramatic increase in later life of multiple forms of illness might reflect the outcome of a unitary process, of so-far unknown biochemical nature, that proceeds at a species-specific rate to increase the risk of many forms of disease and disability in parallel. We have previously reported the results of genetic linkage analyses documenting the ability of alleles at D9Mit110, D10Mit15, and D12Mit167, and an allele pair at D2Mit58 and D16Mit182 to predict longevity in mice bred as the progeny of (BALB/cJ x C57BL/6J)F1 mothers and (C3H/HeJ x DBA/2J)F1 fathers (the UM-HET3 stock). Here we report the results of post hoc analyses to test the hypothesis that the genes that extend the life span of mice dying of neoplastic diseases also extend the life span of mice that die of nonneoplastic causes. In all four cases we find that the genotype associated with increased survival in mice dying of cancer is also associated for a similar degree of life span extension in mice dying of other causes. For D9Mit110 and the combination of D2Mit58 and D16Mit182, the difference is statistically significant in both the neoplastic and nonneoplastic mouse groups. The data support the hypothesis that many forms of late-life disease may be influenced by shared pathophysiologic mechanisms that are under coordinated genetic control. PMID- 11773201 TI - Mouse loci associated with life span exhibit sex-specific and epistatic effects. AB - We have looked for genetic predictors of life span in a sibship of mice created as a four-way cross among inbred grandparental strains BALB/cJ, C57BL/6J, C3H/HeJ, and DBA/2J. To minimize the potential confounding effects of loci that influence early-life illnesses only, we conducted two analyses: one involving all the mice, and the other using a data set from which the first 20% of the deaths were excluded. The two strongest associations reach experimentwise significance levels (p <.01) when tested on the 80% of the mice with the longest life spans. Surprisingly, three of the four strongest associations showed sex-specific effects, with an influence on life span of either male or female mice, but not both. Epistatic interactions among the loci were also identified. The life-span effect of a locus on chromosome 10 (D10Mit15) exhibited epistatic interactions with loci on chromosomes 9 and 16 (D9Mit10 and D16Mit182). In a second example, a locus on chromosome 12 (D12Mit167) depended on the specific combination of alleles inherited from both male and female parents. Our results show that the common laboratory mouse strains are polymorphic at loci that produce substantial differences in life span and that these effects can be sex specific and conditional on alleles inherited at other loci. PMID- 11773202 TI - Leukocyte lysosomal enzymes in Alzheimer's disease and Down's syndrome. AB - Previous studies suggested the possibility of accelerated lysosomal degradation of brain gangliosides in Alzheimer's disease (AD). As AD pathology affects both neural and nonneural tissues, the aim of this study was to determine possible changes of glycosphingolipid metabolism in available peripheral cells in AD and Down's syndrome (DS). The activities of several lysosomal enzymes involved in catabolism of gangliosides and sulfatides were measured in leukocytes from subjects with dementia of the Alzheimer type, DS, and age-matched controls, by fluorimetry and spectrophotometry using specific substrates. The results showed a statistically significant increase of beta-galactosidase activity in both dementia of the Alzheimer type and DS leukocytes when compared with age-matched controls (p <.01 and p <.05, respectively; Student's t test). Not significantly increased activities of beta-galactosidase, beta-hexosaminidase, beta hexosaminidase A, and slightly decreased activity of arylsulfatase A were observed in control leukocytes with aging. Our results indicate that a metabolic dysfunction and the acceleration of at least some lysosomal catabolic pathways are present in AD and DS nonneural cells. PMID- 11773203 TI - Preservation of cardiolipin content during aging in rat heart interfibrillar mitochondria. AB - Aging selectively decreases the rate of oxidative phosphorylation in the interfibrillar population of cardiac mitochondria (IFM) located between the myofibers. In contrast, subsarcolemmal mitochondria (SSM), located below the plasma membrane, remain unaffected. IFM from elderly (24-month-old) Fischer 344 rats have a decreased specific activity of complexes III and IV. Complexes III and IV require an inner mitochondrial membrane lipid environment enriched in the oxidatively sensitive phospholipid cardiolipin for maximal activity. We asked if aging decreases the content or alters the composition of cardiolipin as a potential mechanism of the aging defect in IFM. The content and composition of mitochondrial phospholipids were measured in SSM and IFM from adult and aging rat hearts. Aging did not alter the content of mitochondrial phospholipids, including cardiolipin, in either population of mitochondria. The composition of cardiolipin based on characterization of both acyl group and the individual molecular species of cardiolipin was also unaltered by aging. Lipid-mediated oxidative modification of complex III subunits was not detected, making cardiolipin-derived oxidative damage to complex III unlikely. Thus, alterations in cardiolipin are not the mechanism for the aging defect in IFM in Fischer 344 rats. PMID- 11773204 TI - Erythromycin slows aging of Saccharomyces cerevisiae. AB - Life span was measured by counting budding cycles in cohorts of yeast cells treated with erythromycin, paraquat, or geneticin. Paraquat treatment increases oxidative stress; geneticin treatment increases errors during cytoplasmic protein synthesis. Treating with either or both compounds resulted in shorter life spans. Saccharomyces cerevisiae strain K65-3D grown in 16 microg/ml erythromycin, a treatment that results in more accurate protein synthesis by bacteria, had a mean life span that was significantly longer (27%) than that of untreated yeast cells. The life spans of petite variants with no detectable respiratory activity or extranuclear DNA were not affected by this dose of erythromycin, which appeared, therefore, to exert its effect on aging by means of mitochondria. Fitting the data to Weibull and Gompertz distributions allowed calculation of an accelerated life model that relates life span to dose of erythromycin. PMID- 11773205 TI - Drugs, aging, and the future. PMID- 11773206 TI - Relation between vitamin D, physical performance, and disability in elderly persons. AB - BACKGROUND: The aim of this study was to evaluate the relationships between vitamin D, functional status, and disability in a sample of elderly, community dwelling subjects. METHODS: Serum values of 25-hydroxyvitamin D (25[OH] D) and albumin were determined in all participants. Anthropometric measures were obtained, and body composition was assessed using dual-energy x-ray absorptiometry. Arm and leg isometric strength was tested. Reported disability was evaluated using a modified version of the Activities of Daily Living Scale and physical performance with the 6-minute walking test and two items of the Short Form 36 Health Survey Questionnaire (SF-36). RESULTS: A significantly higher prevalence of hypovitaminosis D, defined as level of 25(OH)D < 37.5 nmol/l, was observed in women than in men (55.4% and 35.1%, respectively; p <.001). In women, 25(OH)D was significantly associated with muscular strength and levels of physical function as assessed by SF-36. After adjusting for body mass index, albumin, appendicular fat-free mass, and season, muscle strength was still significantly lower in women with hypovitaminosis D than in those without. Women with reported disability showed significantly lower 25(OH)D values than those without. No relationship between muscular strength, physical function, or reported disability and 25(OH)D was found in men. CONCLUSIONS: In community dwelling elderly women, 25(OH)D is related to muscular function and reported disability. Because of the high prevalence of hypovitaminosis D in the elderly population, this association seems to be clinically relevant. PMID- 11773207 TI - Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men. AB - BACKGROUND: Aging is associated with concomitant declines in activity of the growth hormone (GH) and gonadal steroid axes, and in bone mineral density (BMD), in both sexes. Long-term estrogen replacement slows bone loss and prevents fractures in postmenopausal women, whereas the effects of supplementation of GH or testosterone on bone metabolism and BMD in aged individuals remains uncertain. METHODS: Using a randomized, placebo-controlled, double-blind study design, we investigated the separate and interactive effects of 6 months of administration of recombinant human GH and/or gonadal steroids on bone biochemical markers and BMD in 125 healthy, older (>65 years) women (n = 53) and men (n = 72) with age related reductions in GH and gonadal steroids. RESULTS: In women, administration of GH, but not GH + hormone replacement therapy (HRT), increased serum levels of osteocalcin and procollagen peptide (PICP) and increased urinary excretion of deoxypyridinoline (DPD) crosslinks. Urinary calcium excretion decreased after HRT. In men, GH, and to a greater extent GH + T, increased osteocalcin. GH increased serum PICP, and GH + T increased urinary DPD. Urinary calcium excretion was unaffected by hormone treatment in men. In women, administration of HRT and GH + HRT, but not GH, increased BMD at the lumbar spine, femoral neck, and distal radius. In men, GH + T led to a small decrease in BMD at the proximal radius; there were no other significant effects of hormone administration on BMD. CONCLUSIONS: These data suggest that short-term administration of HRT exerts beneficial effects on bone metabolism and BMD in postmenopausal women, which are not significantly altered by the coadministration of GH. In andropausal men, T administration to achieve physiologic levels did not result in significant effects on bone metabolism or BMD, whereas GH + T increased one marker of bone formation and decreased one marker of bone resorption. Given the known biphasic actions of GH on bone and the apparent favorable biochemical effects of GH + T in men, the longer-term effects of GH + T on BMD in aged men remain to be clarified. PMID- 11773208 TI - Waist circumference and weight change are associated with disability among elderly Hispanics. AB - BACKGROUND: Studies have suggested that both high and low body mass index (BMI) and weight change are related to functional disability in elderly populations. Elderly Hispanics have a high prevalence of both obesity and disability, yet few studies have examined their interrelationship in this population. Therefore, we examined these relationships in a mostly Puerto Rican group of Hispanic elders. METHODS: We investigated associations between a three-level disability score created from responses to a questionnaire on activities of daily living and BMI, waist circumference (WC), and weight change since age 50, using the proportional odds model in a cross-sectional study of 763 elderly Hispanics, aged 60 to 92 years, residing in Massachusetts. RESULTS: After adjusting for potential confounders, men with a WC > or =109.3 cm (vs <90 cm), or with a reported weight loss of -0.32 to -0.01 kg/year, or a weight gain > or =0.55 kg/year since age 50 (vs relatively stable weight, -0.01 to +0.21 kg/year [y]) were each significantly associated with an approximately threefold higher risk for greater disability. Women with a BMI > or =35 kg/m(2) were almost four times as likely to have higher disability as those with a BMI of 20 to 25 kg/m(2). Compared with women with a WC < or =85.2 cm, those with a WC of 91.5 to 106.6 cm were two times more likely, and those with a WC > or =106.6 cm were five times more likely, to have higher disability scores. Compared with relatively stable weight (-0.05 to +0.23 kg/y), weight gain > or =0.23 kg/year was associated with a twofold higher risk of greater disability among women. When BMI and WC were included in the same model, WC, but not BMI, remained significantly associated with disability. CONCLUSIONS: Abdominal obesity (WC > or =109.3 cm for men, or WC > or =91.5 cm for women) and weight gain > or =0.55 kg/year after age 50 in men or > or =0.23 kg/year in women may increase the risk of disability among elderly Hispanics. PMID- 11773209 TI - Effects of moderate-intensity exercise on physiological, behavioral, and emotional responses to family caregiving: a randomized controlled trial. AB - BACKGROUND: The study objective was to determine the health and quality-of-life effects of moderate-intensity exercise among older women family caregivers. METHODS: This 12-month randomized controlled trial involved a volunteer sample of 100 women aged 49 to 82 years who were sedentary, free of cardiovascular disease, and caring for a relative with dementia. Participants were randomized to 12 months of home-based, telephone-supervised, moderate-intensity exercise training or to an attention-control (nutrition education) program. Exercise consisted of four 30- to 40-minute endurance exercise sessions (brisk walking) prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill exercise heart rate. Main outcomes were stress-induced cardiovascular reactivity levels, rated sleep quality, and reported psychological distress. RESULTS: Compared with nutrition participants (NU), exercise participants (EX) showed significant improvements in the following: total energy expenditure (baseline and post-test means [SD] for EX = 1.4 [1.9] and 2.2 [2.2] kcal/kg/day; for NU = 1.2 [1.7] and 1.2 [1.6] kcal/kg/day; p <.02); stress-induced blood pressure reactivity (baseline and post-test systolic blood pressure reactivity values for EX = 21.6 [12.3] and 12.4 [11.2] mm Hg; for NU = 17.9 [10.2] and 17.7 [13.8] mm Hg; p <.024); and sleep quality (p <.05). NU showed significant improvements in percentages of total calories from fats and saturated fats relative to EX (p values <.01). Both groups reported improvements in psychological distress. Conclusions. Family caregivers can benefit from initiating a regular moderate intensity exercise program in terms of reductions in stress-induced cardiovascular reactivity and improvements in rated sleep quality. PMID- 11773210 TI - Motor performance in relation to age, anthropometric characteristics, and serum lipids in women. AB - BACKGROUND: The relationships between motor performance and age, anthropometric characteristics, and serum lipids were studied in a population-based sample of women (N = 865). METHODS: Motor performance was measured by a precise laboratory test, the Postural-Locomotion-Manual test, using an optoelectronic technique. Anthropometric measurements included body mass index (BMI) and waist-to-hip ratio. Blood samples were drawn for the measurement of total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride concentrations. RESULTS: Motor performance deteriorated with age in a curvilinear way. High BMI, high waist-to-hip ratio, high triglycerides and low HDL cholesterol were all correlated to poor motor performance after adjustment for age, vascular disease, hypertension, diabetes, smoking, physical exercise, and some chronic diseases. Stepwise regression analyses showed that age, waist-to-hip ratio, triglycerides, HDL cholesterol, physical exercise, and vascular diseases were independent predictors of motor performance. CONCLUSIONS: High age, high waist-to-hip ratio, high triglycerides, and low HDL cholesterol were associated with poor motor performance in women. Monitoring abdominal adiposity and serum lipids in clinical work might help us to identify people with early motor impairment and to prevent more severe mobility disability. PMID- 11773211 TI - Prevalence and incidence of cardiovascular disease in 1160 older men and 2464 older women in a long-term health care facility. AB - BACKGROUND: We report the prevalence and incidence of cardiovascular disease in older men and women in a long-term health care facility. METHODS: The prevalence of hypertension, chronic atrial fibrillation, pacemaker rhythm, coronary artery disease (CAD), thromboembolic stroke, and symptomatic peripheral arterial disease (PAD) and the incidence of new coronary events, thromboembolic stroke, and congestive heart failure (CHF) were investigated in 1160 men, mean age 80 +/- 8 years, and in 2464 women, mean age 81 +/- 8 years, in a long-term health care facility. Mean follow-up was 46 +/- 30 months. RESULTS: The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke were similar in men and women. The prevalence of atrial fibrillation was higher in men (16%) than in women (13%; p =.019). The prevalence of PAD was higher in men (32%) than in women (26%; p =.0001). At the 46-month follow-up, the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. CONCLUSIONS: Older men and women in a long-term health care facility have a high prevalence and incidence of cardiovascular disease. The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke and the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. However, the prevalences of atrial fibrillation and of PAD were higher in men than in women. PMID- 11773212 TI - Gait, lower extremity strength, and self-assessed mobility after hip arthroplasty. AB - BACKGROUND: Rehabilitation services after hip arthroplasty (HA) usually occur in the first 6 months following surgery. Reports in the literature suggest that 9 months to several years after HA surgery, patients are generally satisfied with pain relief. However, many express dissatisfaction with their ability to perform domestic and social activities. Reduced walking ability and long-term lower extremity (LE) muscle weakness may contribute to decreased mobility. The purpose of this study was to compare the within-group LE muscle strength, gait, and self assessed functional mobility in adults 9 months to 6 years after HA surgery to age- and gender-matched controls. METHODS: Thirty subjects (15 HA and 15 control) were studied. LE muscle strength was assessed using the Spark handheld dynamometer. Gait parameters were measured using the GAITMAT II, and self assessed mobility was evaluated using the hip-rating questionnaire. RESULTS: The HA group walked significantly more slowly than the control group at maximum walking speed. The operative LE of the HA group had less muscle strength than the nonoperative LE, and the hip abductors were the most affected muscle group in that LE. The HA group scored lower in the domains of impact, pain, and function on the hip-rating questionnaire. CONCLUSION: Because of long-term residual impairments and disabilities noted after HA surgery, intervention beyond the initial post-surgical rehabilitation is needed. PMID- 11773213 TI - Estimation of calorie and protein intake in aged patients: validation of a method based on meal portions consumed. AB - BACKGROUND: Malnutrition is highly prevalent in hospital, mainly in geriatric, wards. Weight loss results from a negative energy balance, a situation where energy intake does not match energy requirements. Estimates of patient calorie consumption are not performed routinely because of technical difficulties. We performed three studies to investigate the meal-portion (MP) method as a tool for estimating calorie and protein intakes in clinical situations. METHODS: The MP method was designed to estimate calorie and protein consumption from the portion of the food items actually eaten by the patient, which is evaluated at the time plates and dishes are cleared away. Study 1 tested accuracy of the MP method in 50 meals by comparison to food weighing. Study 2 evaluated the validity of estimates obtained by a physician, a member of nursing staff, and a dietician in 30 elderly patients. Study 3 evaluated the robustness and feasibility of the method by comparing estimates obtained by nursing staff (after 1 year of practice with no additional training) and that of a dietician. RESULTS: Comparison of estimates and true values (obtained by weighing) showed a mean difference of -2 kcal/-0.8 g of protein from evaluations of one-half portions of food (50 meals) and -7 kcal/-1.0 g of protein from one-quarter portions of food; the difference was only significant for protein and one-quarter portions (p =.03). When evaluations were performed by observers of different professional categories (nursing staff, physicians, and dieticians) on actual meals consumed by 30 elderly people afflicted with disease, no statistical differences were shown. This interobserver agreement remained, regardless of the cognitive or physical status of the patient. A third study, performed after 1 year of no additional training, showed that the MP method is robust, but prone to clerical errors. CONCLUSIONS: Valid estimates of calorie and protein consumption can be obtained with the MP method, quoting in one-half portions. Quality controls are required both at the food production site (to avoid propagation of errors arising from food composition) and in data collection (to eliminate clerical mistakes). These results suggest that the MP method could be a tool for estimating calorie and protein intakes in many clinical situations. PMID- 11773214 TI - Angiotensin-converting enzyme gene and longevity in the Xin Jiang Uighur autonomous region of China: an association study. AB - BACKGROUND: Longevity can be regarded as a multifactorial trait that results from an interaction between environmental factors and sets of epistatic alleles that have pleiotropic age-dependent effects. The Hotan district in the Xin Jiang Uighur Autonomous region of China is relatively isolated and is well known for an ethnic group that displays marked longevity. METHODS: We performed a correlation study between the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and longevity by comparing distributions of the polymorphism between three different ethnic groups in this region. We obtained data from 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects actually comprised two different age groups: those ranging in age from 59 to 70 years (Uighur older group in Hotan [UOH]) and those ranging in age from 90 to 113 years (Uighur longevity group in Hotan [ULH]). Genomic DNA was extracted from peripheral white blood cells. Polymerase chain reaction was performed to amplify the I/D polymorphic region of the ACE gene. RESULTS: Frequencies of the insertion (I) and deletion (D) alleles were 0.596 (243/408) and 0.404 (165/408) in the Uighur group, 0.606 (130/216) and 0.394 (85/216) in the Kazakh group, and 0.657 (117/178) and 0.343 (61/178) in the Han group. The overall distributions of alleles in these three groups did not differ significantly (chi(2) = 4.6, p =.33). Within the Uighur group, frequency of the D allele was significantly higher in the ULH group (0.448) than in the UOH group (0.355) (p <.04). CONCLUSIONS: This association reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity. Our data may help elucidate the relationship between natural longevity and race difference among individuals in the Xin Jiang Uighur Autonomous region of China. PMID- 11773215 TI - Risk factors for new atherothrombotic brain infarction in older Hispanic men and women. AB - BACKGROUND: We report the prevalence and incidence of atherothrombotic brain infarction (ABI) in older Hispanic men and women in a long-term health care facility. METHODS: The prevalence and incidence of ABI and the association of risk factors with new ABI were investigated in 201 Hispanic men, mean age 79 +/- 8 years, and in 302 Hispanic women, mean age 80 +/- 9 years, in a long-term health care facility. Mean follow-up was 42 +/- 20 months in men and 47 +/- 26 months in women. RESULTS: The prevalence of prior ABI was 33% in Hispanic men and 30% in Hispanic women. The incidence of new ABI was 24% in Hispanic men and 23% in Hispanic women. Significant independent risk factors for new ABI were age (risk ratio = 1.09 in men and 1.08 in women for each increase of 1 year of age), current cigarette smoking (risk ratio = 2.8 in men and 2.7 in women), hypertension (risk ratio = 2.8 in men), diabetes mellitus (risk ratio = 3.5 in men and 5.0 in women), prior ABI (risk ratio = 5.6 in men and 5.5 in women), serum total cholesterol (risk ratio = 1.03 in men and 1.01 in women for each 1 mg/dl increase), and serum high-density lipoprotein (HDL) cholesterol (risk ratio = 1.06 in men and 1.06 in women for each 1 mg/dl decrease). CONCLUSIONS: Significant independent risk factors for new ABI were age, current cigarette smoking, diabetes mellitus, prior ABI, serum total cholesterol, and serum HDL cholesterol (inverse association) in older Hispanic men and women and hypertension in older Hispanic men. PMID- 11773216 TI - The tau protein of oral epithelium increases in Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is an important problem that should be solved in the 21st century. Prior to treatment, a simple and easy diagnostic method using biological markers should be available. As a method to attain this goal, we detected and determined tau protein in oral mucosal epithelium. METHODS: Oral epithelium was exfoliated from 34 patients with AD or 29 patients with vascular dementia, and 33 young and 34 age-matched controls. Western blot was performed for determining the molecular weight of oral tau protein. The tau protein level was determined with an enzyme-linked immunosorbent assay (ELISA) kit for cerebrospinal fluid (CSF). CSF tau was also measured and compared with oral tau. RESULTS: Western blot analysis using an anti-non-phosphorylated tau protein antibody showed two bands, one at 65 Kd and the other at 110 Kd. The tau protein level in oral epithelia showed a significant positive correlation with those in the CSF (p <.05). The patients with AD had significantly higher levels of tau protein than the patients with vascular dementia and the controls (p <.01). AD patients with a younger age at onset of the study showed a higher level of the tau protein than the patients with later age at onset (p <.05). CONCLUSIONS: Like other nonneural tissues, oral epithelium contains small tau and big tau. The tau protein in oral epithelium reflects the pathological changes, as does the CSF tau. Individuals who develop AD may have had high levels of the tau protein in oral mucosal epithelium since early childhood. The tau-protein level in oral epithelia could be helpful in diagnosing AD. PMID- 11773217 TI - The relation between tube feeding and Pseudomonas aeruginosa detection in the oral cavity. PMID- 11773218 TI - Effects of time of day on age differences in working memory. AB - This study investigated the hypothesis that the influence of time of day on the efficiency of working memory is greater for older than younger adults. Groups of younger and older adults performed a working memory task on 4 consecutive days, twice in the morning and twice in the evening. Objective (body temperature) and subjective (alertness ratings) measures of arousal were taken during each session. Temperature increased across the day equally for younger and older adults, whereas alertness ratings were higher in the morning for older adults and in the evening for younger adults. The efficiency of the access and deletion functions paralleled the subjective alertness rating for younger and older adults, and age-related differences in these functions were greater when individuals were tested at nonoptimal times of day. The efficiency of the response inhibition function was similar for younger and older adults and paralleled changes in body temperature. PMID- 11773219 TI - Effects of processing style and age on schema acquisition. AB - Age differences in schema acquisition were examined using a task in which participants read paragraphs about a character and learned to predict his behavior. Successful performance depended on learning which information in the paragraphs was related to the behavior. Because these predictive traits were arbitrarily selected, prior experience was of no benefit. Twenty-eight young adults (ages 18 to 25) and 28 older adults (ages 60 to 80) participated in this experiment. The young adults performed better overall than the older adults. However, when we reexamined the data by considering processing style (i.e., whether individuals relied on a data-driven or conceptually driven processing style), we found that young and older adults who tested specific hypotheses were similar, whereas the older adults who tried to rely on general impressions performed poorly. Findings indicate that it is critical to determine how people approach cognitive tasks and that some older adults are likely to engage in conceptually driven processing regardless of its relevance to a particular task. PMID- 11773220 TI - Psychometric properties of a new metamemory questionnaire for older adults. AB - Subjective memory ratings provide information that is distinct from objective memory performance, and there is a need for reliable and valid metamemory measures. The Multifactorial Memory Questionnaire (MMQ), developed to assess separate dimensions of memory ratings that are applicable to clinical assessment and intervention, includes scales of Contentment (i.e., affect regarding one's memory), Ability (i.e., self-appraisal of one's memory capabilities), and Strategy (i.e., reported frequency of memory strategy use). Among a group of 115 older adults, analyses revealed excellent content validity, factorial validity, test-retest and intratest reliability, convergent and discriminant construct validity, and independence from demographic variables. The psychometric strengths of the MMQ, together with descriptive statistics provided for healthy older adults, make this questionnaire useful in both clinical and research settings. PMID- 11773221 TI - Social context effects on story recall in older and younger women: does the listener make a difference? AB - The story-recall performance of older and younger women was examined within an oral story-retelling context with two listener conditions. Forty-eight older women (M age = 67.81 years; SD = 2.62) and 47 younger women (M age = 20.47 years; SD = 1.53) were asked to learn one of two stories with the goal to retell the story from memory either to an experimenter or to a young child. Did the listener make a difference in story recall? Yes. Although age-group differences in propositional recall favoring the younger women occurred when an experimenter was the listener, there were no age-group differences when a child was the listener. In addition, when a child was listening, both older and younger tellers adapted their narratives by producing more elaborations and repetitions, as well as by simplifying the more complex of the two stories. Across stories, however, the older tellers adjusted the complexity of their retellings to the age of their listeners more than did the younger tellers. Results highlight the importance of considering the social context of remembering in memory-aging research. PMID- 11773222 TI - Preserved olfactory cuing of autobiographical memories in old age. AB - The authors investigated whether olfactory cues can facilitate memory retrieval and whether they retain their effectiveness in old age. In Phase 1, 57 young and 57 old adults (mean ages of 21 and 84 years, respectively) were asked to recall autobiographical memories associated with each of six cue words. In Phase 2, the same words were presented again with instructions to recall new memories; on this second occasion, half of the words were accompanied by their appropriate odors. Both age groups recalled more than twice as many memories in Phase 2 with the odor than without the odor, providing evidence for substantial olfactory cuing that is remarkably intact in old age. PMID- 11773223 TI - Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries. AB - A Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) was created. The English-American version of CERAD clinical and neuropsychological assessment batteries was translated into Korean, and the psychometrical properties of the cognitive tests in the CERAD-K were established. In the translation, including back-translation, the basic structures of all measures in the original CERAD batteries were maintained. The CERAD-K was administered in a standardized manner to 106 dementia patients (aged 70.4 +/- 8.1 years), including 78 Alzheimer's disease (AD) patients, and 186 controls (aged 68.4 +/- 4.6 years) who were recruited from 3 university hospitals and 2 elderly welfare centers. The cognitive tests in the CERAD-K successfully differentiated controls from the dementia patients and from the AD patients. They also showed substantial interrater reliability and 1-month test-retest reliability. The CERAD-K is an equally reliable and valid equivalent for the English version of the CERAD clinical and neuropsychological assessment batteries. PMID- 11773224 TI - Age-related kinematic differences as influenced by task difficulty, target size, and movement amplitude. AB - Fifteen older adults (M = 68 years old) and 15 young adults (M = 23 years old) participated in a speed-accuracy task in which aiming movements were performed on a digitizing tablet to assess movement slowing and variability in older adults. Target-size and movement amplitude influences were analyzed separately to determine if they affected the performance of the young and older adults differently. When target size was increased, older adults did not increase the relative distance traveled in the primary submovement. When movement amplitude was increased, older adults did not scale movement velocities to the same magnitude as young adults did. Both the inability to scale velocity and the inability to increase the relative distance traveled in the primary submovement contribute to slower, more variable movements observed in older adults depending on task parameters. Thus, these data reveal that manipulation of target size and movement amplitude yield two distinct factors that contribute to slowness of movement in older adults. PMID- 11773225 TI - Gaze aversion: spared inhibition for visual distraction in older adults. AB - Our everyday environment is filled with irrelevant and potentially distracting information. Recent research has shown that during retrieval people tend to look away from distraction or close their eyes and that averting one's gaze benefits retrieval. We examined the extent to which there are age-related differences in the benefits of gaze aversion and whether the benefits of gaze aversion extend to encoding. Relative to looking at complex stimuli, closing the eyes and looking at simple stimuli produced reliable improvements in memory for both younger and older adults at both encoding and retrieval. Contrary to the expectation that older adults have general inhibitory deficits, the benefits of gaze aversion were similar for younger and older adults at both encoding and retrieval. These results are consistent with the view that older adults have spared inhibitory functioning for distraction appearing in fixed locations. PMID- 11773226 TI - The revised scale for caregiving self-efficacy: reliability and validity studies. AB - Two samples of family caregivers (Study 1: N = 169; Study 2: N = 145) of cognitively impaired older adults were used to revise, extend, and evaluate a measure of perceived self-efficacy for caregiving tasks. The Revised Scale for Caregiving Self-Efficacy measures 3 domains of caregiving self-efficacy: Obtaining Respite, Responding to Disruptive Patient Behaviors, and Controlling Upsetting Thoughts. The 3 subscales show strong internal consistency and adequate test-retest reliability. Construct validity is supported by relationships between these 3 facets of perceived caregiving efficacy and depression, anxiety, anger, perceived social support, and criticism expressed in speech samples. The Revised Scale for Caregiving Self-Efficacy has potential uses for both research and clinical purposes. PMID- 11773227 TI - Negative life events and depression in elderly persons: a meta-analysis. AB - In a meta-analysis of 25 studies, the relationship of both specific types of negative life events and the total number of experienced events to depression in old age was studied. Almost all negative life events appeared to have a modest but significant relationship with depression. The total number of negative life events and the total number of daily hassles appeared to have the strongest relationship with depression (respectively, combined r =.15, n = 5,037, and combined r =.41, n = 461), whereas sudden unexpected events were the only cluster of negative life events that seemed not to be related to depression scores (combined r =.05, n = 857). These findings suggest that providers and developers of intervention and prevention programs for elderly people should pay attention to the occurrence of negative life events. Special attention should be given to elderly people who have experienced an accumulation of stressful events and daily hassles, because they seem to be a group at greater risk. PMID- 11773228 TI - Reciprocity in parent-child relations over the adult life course. AB - OBJECTIVES: This research assessed how parents' transfers of sentiment, time, and financial assets to their adolescent/young adult children affect the children's propensity in middle age to provide social support to their aging parents. We tested whether the mechanism of long-term intergenerational exchange is better modeled as a return on investment, an insurance policy triggered by the longevity or physical frailty of parents, or the result of altruistic (or other nonreciprocal) motivations on the part of adult children. METHODS: Models were examined with 6 waves of data from the University of Southern California Longitudinal Study of Generations. The sample consisted of 501 children who participated in the 1971 survey and who had at least 1 parent surviving in 1985. Growth curve modeling was applied to predict average levels and rates of change in social support provided to mothers and fathers between 1985 and 1997 as a function of early parental transfers of affection, association, and tangible resources to their children. RESULTS: Children who spent more time in shared activities with their mothers and fathers in 1971 provided more support to them on average. Receiving greater financial support from parents in 1971 raised the marginal rate at which support provided by children increased over time. Maternal health operated synergistically with early affection to produce greater levels of support. Both levels and rates of increase in support from children were positive, even for children who received no early transfers from their parents. DISCUSSION: The results offer some support for investment, insurance, and altruistic models of intergenerational exchange. Sharing time in activities provides a direct return to the parent that is characteristic of an investment strategy, whereas financial transfers provide a time-contingent return that is characteristic of an insurance mechanism. That affection triggers greater support to more functionally impaired mothers suggests that emotionally investing in children as a health insurance mechanism may be based on the greater moral equity accorded to mothers. The motivation of adult children to provide social support to their older parents is partially rooted in earlier family experiences and guided by an implicit social contract that ensures long-term reciprocity. PMID- 11773229 TI - Self-gain and self-loss among African American and white caregivers. AB - OBJECTIVES: This study compared the effects of a traditional ideology of care and role conflict on the intrinsic rewards (self-gain) and consequences (self-loss) of caregiving among African Americans and Whites. METHODS: Using a cross sectional telephone survey of caregivers in North Carolina (n = 481), the authors performed a structural equation groups analysis to assess the equality of an a priori caregiving model for African Americans (n = 257) and Whites (n = 224). RESULTS: Despite a stronger preference for family care among African Americans, traditional caregiving ideology was associated with more self-gain among Whites only; there was no relationship between preference for family care and self-loss for either group. Furthermore, role conflict was unrelated to self-gain but was related to more self-loss for both groups. Three additional relationships differed between African Americans and Whites: age and self-gain, gender and self gain, and care recipient depression and role conflict. However, 12 proposed relationships were statistically significant and equivalent for African Americans and Whites. DISCUSSION: The findings suggest that contextual elements that influence preference for family care and role conflict are almost identical for African Americans and Whites. Caregiver demographics are associated with caregiving ideology, whereas care recipient frailty is related to role conflict. However, there are differences between African American and White caregivers, which primarily stem from the role of age, gender, and preference for family care with self-gain. PMID- 11773230 TI - Whose education counts? The added impact of adult-child education on physical functioning of older taiwanese. AB - OBJECTIVES: Research has implicated education as an important predictor of physical functioning in old age. Older adults in Taiwan tend to experience tight familial integration and high rates of adult-child coresidency-much more so than is typical in Western cultures-which might imply additional influences stemming from the education of children. This could arise in a number of ways; for instance, through the sharing of health-related information between child and parent, the quality of caregiving efforts, monetary assistance for medical and other services, or other psychosocial avenues. Despite this probable association, such hypotheses have rarely been tested. In this study, a nationally representative survey of older Taiwanese was used to examine these concurrent effects. METHODS: Outcome variables include the existence of any functional limitations (dichotomously measured) and the severity of functional disorders (ordinally measured). Dichotomous and ordinal logistic models were used. RESULTS: Results suggest that, after adjusting for age, sex, and other factors, both child and respondent education associate with the existence of limitations, but the child's education is more important than the parent's when predicting severity of limitations. DISCUSSION: This implies that models ignoring social network characteristics in determining health outcomes of older adults may be misspecified, at least in some non-Western societies, and calls for further testing in other societies as well. PMID- 11773231 TI - Theories on coping with loss: the impact of social support and self-esteem on adjustment to emotional and social loneliness following a partner's death in later life. AB - OBJECTIVES: This longitudinal study focused on the role of self-esteem and social support in adjustment to loneliness experienced by bereaved elderly persons. This study also examined the contributions of a general and a specific coping theory toward explaining loneliness. A distinction has been made between emotional loneliness and social loneliness/perceived support. The theory of mental incongruity predicts that the presence of more favorable conditions, such as higher self-esteem or more social support, results in less loneliness (i.e., less incongruity). According to the theory of relational loneliness, the partner's death leads to a loss of identity, thus increasing emotional loneliness, and social support does not mitigate emotional loneliness following a loss. METHODS: In total, 101 participants, aged 55-89 years, were interviewed before and after their partners' deaths. RESULTS: Findings were ambiguous with regard to both theories. As hypothesized, partner loss lowered self-esteem, resulting in higher emotional loneliness and social loneliness, that is, perception of less support. Supportive personal relations reduced emotional loneliness. The presence of close friends, however, seemed to increase emotional and social loneliness (i.e., decrease perceived support) in the long term, particularly among bereaved participants with lower self-esteem. DISCUSSION: The findings highlight the need to integrate theoretical concepts. In explaining adjustment to a partner's death, attention should be paid to underlying mechanisms relevant to the restoration process (e.g., identity change) and the ways in which the adjustment process can be improved (e.g., intimate relationships) or impeded (e.g., dependency sustaining relationships). PMID- 11773232 TI - Socioeconomic position across the lifecourse and cognitive function in late middle age. AB - OBJECTIVES: To examine the influence of childhood and adult socioeconomic position, socioeconomic mobility, and cumulative disadvantage across the lifecourse on cognitive function in late middle age. METHODS: Cross-sectional population-based study of 486 men age 58 and 64 from eastern Finland. Respondent's socioeconomic position in childhood was measured using parent's education and occupation, and respondent's position in adulthood was indicated by attained education and personal income. Cognitive function was assessed using five neuropsychological tests: Trail Making, Selective Reminding, Verbal Fluency, Visual Reproduction, and the Mini-Mental State Exam. RESULTS: Each indicator of socioeconomic position made statistically independent contributions to levels of cognitive function: Respondents from poor childhood backgrounds, and those who attained a limited education and earned a low income, performed worst on each test. Men who occupied a disadvantaged socioeconomic position in childhood and then experienced upward mobility over the lifecourse exhibited better cognitive performance than those with similar socioeconomic origins but limited or no upward mobility. Conversely, men from advantaged childhood backgrounds who later in life experienced downward mobility scored poorer on each cognitive test than their counterparts who remained in the most advantaged groups throughout the lifecourse. There was a strong, graded association between cumulative socioeconomic disadvantage and cognitive function: Men who occupied a low socioeconomic position during both childhood and adulthood scored worse on every test than those who occupied a high position at all points in their lives. DISCUSSION: Socioeconomic conditions across all stages of the lifecourse appear to make unique contributions to cognitive function in late middle age. These results also suggest that in terms of cognitive function, origin is not necessarily destiny, as disadvantaged socioeconomic circumstances in childhood may be overcome to some extent by upward mobility later in life. PMID- 11773233 TI - Change in the centrality of women's multiple roles: effects of role stress and rewards. AB - OBJECTIVES: To examine (a) change versus stability over one year in four social roles occupied by 182 midlife women (parent care provider, mother, wife and employee), (b) increases in role stress and increases in role rewards as predictors of change in centrality, and (c) whether increases in stress or increases in rewards were stronger predictors when the 2 were considered simultaneously. METHOD: Interviews were conducted at 2 time points approximately 1 year apart. Participants were asked to rate the personal importance of each role on a scale of 1 to 10. Stress and rewards in each role were also assessed. RESULTS: Analyses revealed considerable change in role centrality, especially in the parent-care and employee roles. Increases in wife and employee stress were associated with decreases in the centrality of these roles, whereas increases in rewards in each of the four roles were related to increases in the centrality of the respective roles. When considered simultaneously, role rewards were stronger predictors of change in centrality than role stress. DISCUSSION: These findings suggest that the centrality of a social role can change over time in response to stressful and rewarding role experiences. PMID- 11773235 TI - Interdomain interactions within ryanodine receptors regulate Ca2+ spark frequency in skeletal muscle. AB - DP4 is a 36-residue synthetic peptide that corresponds to the Leu(2442)-Pro(2477) region of RyR1 that contains the reported malignant hyperthermia (MH) mutation site. It has been proposed that DP4 disrupts the normal interdomain interactions that stabilize the closed state of the Ca(2)+ release channel (Yamamoto, T., R. El-Hayek, and N. Ikemoto. 2000. J. Biol. Chem. 275:11618-11625). We have investigated the effects of DP4 on local SR Ca(2)+ release events (Ca(2)+ sparks) in saponin-permeabilized frog skeletal muscle fibers using laser scanning confocal microscopy (line-scan mode, 2 ms/line), as well as the effects of DP4 on frog SR vesicles and frog single RyR Ca(2)+ release channels reconstituted in planar lipid bilayers. DP4 caused a significant increase in Ca(2)+ spark frequency in muscle fibers. However, the mean values of the amplitude, rise time, spatial half width, and temporal half duration of the Ca(2)+ sparks, as well as the distribution of these parameters, remained essentially unchanged in the presence of DP4. Thus, DP4 increased the opening rate, but not the open time of the RyR Ca(2)+ release channel(s) generating the sparks. DP4 also increased [(3)H]ryanodine binding to SR vesicles isolated from frog and mammalian skeletal muscle, and increased the open probability of frog RyR Ca(2)+ release channels reconstituted in bilayers, without changing the amplitude of the current through those channels. However, unlike in Ca(2)+ spark experiments, DP4 produced a pronounced increase in the open time of channels in bilayers. The same peptide with an Arg(17) to Cys(17) replacement (DP4mut), which corresponds to the Arg(2458)-to-Cys(2458) mutation in MH, did not produce a significant effect on RyR activation in muscle fibers, bilayers, or SR vesicles. Mg(2)+ dependence experiments conducted with permeabilized muscle fibers indicate that DP4 preferentially binds to partially Mg(2)+-free RyR(s), thus promoting channel opening and production of Ca(2)+ sparks. PMID- 11773234 TI - In vivo airway surface liquid Cl- analysis with solid-state electrodes. AB - The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl-] in the "thin" ASL (approximately 30 microm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl-] in vivo. In initial experiments, the electrode measured [Cl-] in physiologic salt solutions, small volume (7.6 microl) test solutions, and in in vitro cell culture models, with > or =93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl- measurements were made in the following airway regions and species. First, ASL [Cl-] was measured in normal human nasal cavity and averaged 117.3 +/- 11.2 mM (n = 6). Second, ASL [Cl-] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 +/- 1.8 mM; (n = 6) and 126.9 +/- 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 +/- 4.2 mM (n = 13); and monkey bronchus = 112.3 +/- 10.9 mM (n = 3). Third, Cl- measurements were made in small (1-2 mm) diameter airways of the rabbit (108.3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology. PMID- 11773236 TI - K depletion enhances the extracellular Ca2+-induced inhibition of the apical K channels in the mTAL of rat kidney. AB - We have shown previously that raising extracellular Ca(2)+ inhibited the apical 70-pS K channel in the thick ascending limb (TAL; Wang, W.H., M. Lu, and S.C. Hebert. 1996. Am. J. Physiol. 270:C103-C111). We now used the patch-clamp technique to study the effect of increasing the extracellular Ca(2)+ on the 70-pS K channel in the mTAL from rats on a different K diet. Increasing the extracellular Ca(2)+ from 10 microM to 0.5, 1, and to 1.5 mM in the mTAL from rats on a K-deficient (KD) diet inhibited the channel activity by 30, 65, and 90%, respectively. In contrast, raising the extracellular Ca(2)+ to 1.5 mM had no significant effect on channel activity in the mTAL from animals on a high K (HK) diet and further increasing the extracellular Ca(2)+ to 2.5, 3.5, and 5.5 mM decreased the channel activity by 29, 55, and 90%, respectively. Inhibition of the cytochrome P450 monooxygenase completely abolished the effect of the extracellular Ca(2)+ on channel activity in the mTAL from rats on a different K diet. In contrast, blocking cyclooxygenase did not significantly alter the responsiveness of the 70-pS K channel to the extracellular Ca(2)+. Moreover, addition of sodium nitropruside, a nitric oxide (NO) donor, not only increased the channel activity, but also blunted the inhibitory effect of the extracellular Ca(2)+ on the 70-pS K channel and decreased 20-hydroxyeicosatetraenoic acid (20 HETE) concentration in the mTAL from rats on a KD diet. In contrast, inhibiting NOS with L-NAME enhanced the inhibitory effect of the extracellular Ca(2)+ on the channel activity and increased 20-HETE concentration in the mTAL from rats on a high K diet. Western blot has further shown that the expression of inducible NO synthase (iNOS) is significantly higher in the renal medulla from rats on an HK diet than that on a KD diet. Also, addition of S-nitroso-N-acetylpenicillamine abolished the inhibitory effect of arachidonic acid on channel activity in the mTAL, whereas it did not block the inhibitory effect of 20-HETE. We conclude that a low dietary K intake increases the sensitivity of the 70-pS K channel to the extracellular Ca(2)+, and that a decrease in NOS activity is involved in enhancing the inhibitory effect of the extracellular Ca(2)+ on channel activity in the mTAL during K depletion. PMID- 11773237 TI - Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxin. AB - Pore-blocking toxins are valuable probes of ion channels that underlie electrical signaling. To be effective inhibitors, they must show high affinity and specificity and prevent ion conduction. The 22-residue sea snail peptide, mu conotoxin GIIIA, blocks the skeletal muscle sodium channel completely. Partially blocking peptides, derived by making single or paired amino acid substitutions in mu-conotoxin GIIIA, allow a novel analysis of blocking mechanisms. Replacement of one critical residue (Arg-13) yielded peptides that only partially blocked single channel current. These derivatives, and others with simultaneous substitution of a second residue, were used to elucidate the structural basis of the toxin's blocking action. The charge at residue-13 was the most striking determinant. A positive charge was necessary, though not sufficient, for complete block. Blocking efficacy increased with increasing residue-13 side chain size, regardless of charge, suggesting a steric contribution to inhibition. Charges grouped on one side of the toxin molecule at positions 2, 12, and 14 had a weaker influence, whereas residue-16, on the opposite face of the toxin, was more influential. Most directly interpreted, the data suggest that one side of the toxin is masked by close apposition to a binding surface on the pore, whereas the other side, bearing Lys-16, is exposed to an aqueous cavity accessible to entering ions. Strong charge-dependent effects emanate from this toxin surface. In the native toxin, Arg-13 probably presents a strategically placed electrostatic barrier rather than effecting a complete steric occlusion of the pore. This differs from other well-described channel inhibitors such as the charybdotoxin family of potassium channel blockers and the sodium channel blocking guanidinium toxins (tetrodotoxin and saxitoxin), which appear to occlude the narrow part of the pore. PMID- 11773238 TI - A metabotropic glutamate receptor regulates transmitter release from cone presynaptic terminals in carp retinal slices. AB - The role of group III metabotropic glutamate receptors (mGluRs) in photoreceptor H1 horizontal cell (HC) synaptic transmission was investigated by analyzing the rate of occurrence and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in H1 HCs uncoupled by dopamine in carp retinal slices. Red light steps or the application of 100 microM cobalt reduced the sEPSC rate without affecting their peak amplitude, which is consistent with hyperpolarization or the suppression of Ca(2+) entry into cone synaptic terminals reducing vesicular transmitter release. Conversely, postsynaptic blockade of H1 HC AMPA receptors by 500 nM CNQX reduced the amplitude of sEPSCs without affecting their rate. This analysis of sEPSCs represents a novel methodology for distinguishing between presynaptic and postsynaptic sites of action. The selective agonist for group III mGluRs, l-2-amino-4-phosphonobutyrate (L-APB or L-AP4; 20 microM), reduced the sEPSC rate with a slight reduction in amplitude, which is consistent with a presynaptic action on cone synaptic terminals to reduce transmitter release. During L-APB application, recovery of sEPSC rate occurred with 500 microM (s)-2 methyl-2-amino-4-phosphonobutyrate (MAP4), a selective antagonist of group III mGluR, and with 200 microM 4-aminopyridine (4-AP), a blocker of voltage-dependent potassium channels. Whole-cell recordings from cones in the retinal slice showed no effect of L-APB on voltage-activated Ca(2+) conductance. These results suggest that the activation of group III mGluRs suppresses transmitter release from cone presynaptic terminals via a 4-AP-sensitive pathway. Negative feedback, operating via mGluR autoreceptors, may limit excessive glutamate release from cone synaptic terminals. PMID- 11773239 TI - Beta 2-adrenergic receptor signaling acts via NO release to mediate ACh-induced activation of ATP-sensitive K+ current in cat atrial myocytes. AB - In atrial myocytes, an initial exposure to isoproterenol (ISO) acts via cAMP to mediate a subsequent acetylcholine (ACh)-induced activation of ATP-sensitive K(+) current (I(K,ATP)). In addition, beta-adrenergic receptor (beta-AR) stimulation activates nitric oxide (NO) release. The present study determined whether the conditioning effect of beta-AR stimulation acts via beta(1)- and/or beta(2)-ARs and whether it is mediated via NO signaling. 0.1 microM ISO plus ICI 118,551 (ISO beta(1)-AR stimulation) or ISO plus atenolol (ISO-beta(2)-AR stimulation) both increased L-type Ca(2+) current (I(Ca,L)) markedly, but only ISO-beta(2)-AR stimulation mediated ACh-induced activation of I(K,ATP). 1 microM zinterol (beta(2)-AR agonist) also increased I(Ca,L) and mediated ACh-activated I(K,ATP). Inhibition of NO synthase (10 microM L-NIO), guanylate cyclase (10 microM ODQ), or cAMP-PKA (50 microM Rp-cAMPs) attenuated zinterol-induced stimulation of I(Ca,L) and abolished ACh-activated I(K,ATP). Spermine-NO (100 microM; an NO donor) mimicked beta(2)-AR stimulation, and its effects were abolished by Rp cAMPs. Intracellular dialysis of 20 microM protein kinase inhibitory peptide (PKI) abolished zinterol-induced stimulation of I(Ca,L). Measurements of intracellular NO ([NO](i)) using the fluorescent indicator DAF-2 showed that ISO beta(2)-AR stimulation or zinterol increased [NO](i). L-NIO (10 microM) blocked ISO- and zinterol-induced increases in [NO](i). ISO-beta(1)-AR stimulation failed to increase [NO](i). Inhibition of G(i)-protein by pertussis toxin significantly inhibited zinterol-mediated increases in [NO](i). Wortmannin (0.2 microM) or LY294002 (10 microM), inhibitors of phosphatidylinositol 3'-kinase (PI-3K), abolished the effects of zinterol to both mediate ACh-activated I(K,ATP) and stimulate [NO](i). We conclude that both beta(1)- and beta(2)-ARs stimulate cAMP. beta(2)-ARs act via two signaling pathways to stimulate cAMP, one of which is mediated via G(i)-protein and PI-3K coupled to NO-cGMP signaling. Only beta(2) ARs acting exclusively via NO signaling mediate ACh-induced activation of I(K,ATP). NO signaling also contributes to beta(2)-AR stimulation of I(Ca,L). The differential effects of beta(1)- and beta(2)-ARs can be explained by the coupling of these two beta-ARs to different effector signaling pathways. PMID- 11773240 TI - Voltage-controlled gating at the intracellular entrance to a hyperpolarization activated cation channel. AB - Hyperpolarization-activated cation (HCN) channels regulate pacemaking activity in cardiac cells and neurons. Our previous work using the specific HCN channel blocker ZD7288 provided evidence for an intracellular activation gate for these channels because it appears that ZD7288, applied from the intracellular side, can enter and leave HCN channels only at voltages where the activation gate is opened (Shin, K.S., B.S. Rothberg, and G. Yellen. 2001. J. Gen. Physiol. 117:91-101). However, the ZD7288 molecule is larger than the Na(+) or K(+) ions that flow through the open channel. In the present study, we sought to resolve whether the voltage gate at the intracellular entrance to the pore for ZD7288 also can be a gate for permeant ions in HCN channels. Single residues in the putative pore lining S6 region of an HCN channel (cloned from sea urchin; spHCN) were substituted with cysteines, and the mutants were probed with Cd(2+) applied to the intracellular side of the channel. One mutant, T464C, displayed rapid irreversible block when Cd(2+) was applied to opened channels, with an apparent blocking rate of approximately 3 x 10(5) M(-1)s(-1). The blocking rate was decreased for channels held at more depolarized voltages that close the channels, which is consistent with the Cd(2+) access to this residue being gated from the intracellular side of the channel. 464C channels could be recovered from Cd(2+) inhibition in the presence of a dithiol applied to the intracellular side. The rate of this recovery also was reduced when channels were held at depolarized voltages. Finally, Cd(2+) could be trapped inside channels that were composed of WT/464C tandem-linked subunits, which could otherwise recover spontaneously from Cd(2+) inhibition. Thus, Cd(2+) escape is also gated at the intracellular side of the channel. Together, these results are consistent with a voltage-controlled structure at the intracellular side of the spHCN channel that can gate the flow of cations through the pore. PMID- 11773241 TI - On the mechanisms whereby temperature affects excitation-contraction coupling in smooth muscle. AB - Moderate cooling of smooth muscle can modulate force production and may contribute to pathophysiological conditions, but the mechanisms underlying its effects are poorly understood. Interestingly, cooling increases force in rat ureter, but decreases it in guinea pigs. Therefore, this study used ureteric smooth muscle as a model system to elucidate the mechanisms of the effects of cooling on excitation-contraction coupling. Simultaneous recordings of force, intracellular [Ca(2+)], and electrical activity were made in intact ureter and ionic currents measured in isolated cells. The increase in force amplitude in rat ureter with cooling was found to be due to a significant increase in the duration of the Ca(2+) transient. This in turn was due to a marked prolongation of the action potential. In guinea pigs, both these parameters were much less affected by cooling. Examination of membrane currents revealed that differences in ion channel contribution to the action potential underlie these differences. In particular, cooling potentiated Ca(2+)-activated Cl(-) currents, which are present in rat but not guinea pig ureteric smooth muscle, and prolonged the plateau of the action potential and Ca(2+) entry. The force-Ca(2+) relationship revealed that the increased duration of the Ca(2+) transient was sufficient in the rat, but not in the guinea pig, to overcome kinetic lags produced in both species by cooling and potentiate force. Ca(2+) entry and release processes were largely temperature-insensitive, but the rate of relaxation was very temperature sensitive. Effects of cooling on myosin light chain phosphatase, confirmed in experiments using calyculin A, appear to be the predominant mechanisms affecting relaxation. Thus, smooth muscle is diverse in its response to temperature, even when experimental variables, such as the mode of stimulation, are removed. Although the biochemical and mechanical events accompanying contraction are likely to be affected in similar ways by temperature, differences in electrical events lead to subsequent differences in these processes between smooth muscles. PMID- 11773242 TI - Open state destabilization by ATP occupancy is mechanism speeding burst exit underlying KATP channel inhibition by ATP. AB - The ATP-sensitive potassium (K(ATP)) channel is named after its characteristic inhibition by intracellular ATP. The inhibition is a centerpiece of how the K(ATP) channel sets electrical signaling to the energy state of the cell. In the beta cell of the endocrine pancreas, for example, ATP inhibition results from high blood glucose levels and turns on electrical activity leading to insulin release. The underlying gating mechanism (ATP inhibition gating) includes ATP stabilization of closed states, but the action of ATP on the open state of the channel is disputed. The original models of ATP inhibition gating proposed that ATP directly binds the open state, whereas recent models indicate a prerequisite transition from the open to a closed state before ATP binds and inhibits activity. We tested these two classes of models by using kinetic analysis of single-channel currents from the cloned mouse pancreatic K(ATP) channel expressed in Xenopus oocytes. In particular, we combined gating models based on fundamental rate law and burst gating kinetic considerations. The results demonstrate open state ATP dependence as the major mechanism by which ATP speeds exit from the active burst state underlying inhibition of the K(ATP) channel by ATP. PMID- 11773243 TI - Drosophila mediopunctata P elements: a new example of horizontal transfer. AB - Sequences homologous to the P element of Drosophila melanogaster were previously identified in Drosophila mediopunctata, a member of the tripunctata group, subgenus Drosophila. We report here that the P element is present in about three to five copies in the D. mediopunctata genome. While one of the insertion sites appears to be fixed, others may be polymorphic, indicating relatively recent P element activity. Phylogenetic analysis revealed that the D. mediopunctata element belongs to the canonical subfamily of P elements and that divergence of the D. mediopunctata element from other members of this subfamily ranges from 2% to 5% at the nucleotide level. This is the first report of a canonical P element outside the subgenus Sophophora. Based primarily on the striking incongruence between P element and host species phylogenies, the presence of a canonical P element in D. mediopunctata is most likely explained by horizontal transfer between species. PMID- 11773244 TI - Gametic associations between inversion and allozyme polymorphisms in Drosophila buzzatii. AB - Gametic disequilibria between second chromosome polymorphic arrangements and seven linked allozyme loci were estimated in seven populations of Drosophila buzzatii from Argentina. Significant and consistent associations across populations were detected for Est-1, Est-2, Aldox, and XDH: Phenograms based on Nei's genetic distance showed that chromosomes carrying the 2ST arrangement were more similar to each other, irrespective of the population from which they were extracted, than to chromosomes carrying the derived 2J and 2JZ3. Restriction of recombination in heterokaryotypes seems to be the best explanation for the significant linkage disequilibria between inversions and the loci located inside the rearranged segments, for example, Est-1 and Aldox, or close to the break points, for example, Est-2. However, epistatic interactions between Xdh, which is outside the inversions and not near the break points, and loci tightly linked to the inversions, is the most likely explanation for the association between Xdh and chromosomal arrangements. Some of the associations detected in endemic Argentinean populations are coincident with data obtained in colonizing populations of the Old World and Australia. Thus historical processes that took place in the original area of the species' distribution can account for these linkage disequilibria in colonized populations of D. buzzatii. PMID- 11773245 TI - Isolation of a sex-linked DNA sequence in cranes. AB - A female-specific DNA fragment (CSL-W; crane sex-linked DNA on W chromosome) was cloned from female whooping cranes (Grus americana). From the nucleotide sequence of CSL-W, a set of polymerase chain reaction (PCR) primers was identified which amplify a 227-230 bp female-specific fragment from all existing crane species and some other noncrane species. A duplicated versions of the DNA segment, which is found to have a larger size (231-235 bp) than CSL-W in both sexes, was also identified, and was designated CSL-NW (crane sex-linked DNA on non-W chromosome). The nucleotide similarity between the sequences of CSL-W and CSL-NW from whooping cranes was 86.3%. The CSL primers do not amplify any sequence from mammalian DNA, limiting the potential for contamination from human sources. Using the CSL primers in combination with a quick DNA extraction method allows the noninvasive identification of crane gender in less than 10 h. A test of the methodology was carried out on fully developed body feathers from 18 captive cranes and resulted in 100% successful identification. PMID- 11773246 TI - Genetic variability in East Asian dogs using microsatellite loci analysis. AB - An analysis of eight microsatellite loci in 213 animals was performed to define the genetic structure and variability of 11 East Asian native dog populations. Allele diversity, observed heterozygosities, expected heterozygosities, F statistics, G(ST) estimates, number of migrants per generation (Nm), and Nei's DA distance were calculated. Expected mean heterozygosities of Asian native dogs varied within a range of 0.310-0.718 with a mean value of 0.580. In a sample of 11 Asian dogs, the highest genetic diversity was exhibited in the Korean native dogs and the lowest in the Shiba, the Japanese native dog. All populations except the Kishu and Akita showed statistically significant deviation from Hardy Weinberg equilibrium at more than one locus. After corrections for multiple significance tests, deviations over all loci were statistically significant in 7 of 11 dog populations, meaning that Asian dogs are genetically subdivided (global F(ST) = 0.154). Despite the locus-specific deviations, statistically significant departures from the Hardy-Weinberg equilibrium reflect deviations in the direction of heterozygote deficit, the global F(IS) being 0.072. In the neighbor joining and unweighted pair group method with arithmetic mean (UPGMA) dendrograms based on Nei's DA distance, the Korean native breeds (the Sapsaree and the Jindo) were grouped together, then with the Eskimo dog. The two Japanese native dogs (the Hokkaido and the Akita) also clustered together, with moderate bootstrap support. In spite of some deviation, the three-dimensional scattergram based on principal components supported the conclusions suggested by the dendrograms based on Nei's DA distance. From these two analyses, the Korean native dogs formed the closest groups and then showed a close relationship to the Eskimo dogs, reflecting the fact that the Korean native dogs might be originated from dogs in the northern part of Far East Asia. PMID- 11773247 TI - Morphological, cytogenetic, and molecular evidence for introgressive hybridization in birch. AB - Extensive morphological variation of tetraploid birch (Betula pubescens) in Iceland is believed to be due to gene flow from diploid dwarf birch (B. nana) by means of introgressive hybridization. A combined morphological and cytogenetic approach was used to investigate this phenomenon in two geographically separated populations of natural birch woodland in Iceland. The results not only confirmed introgressive hybridization in birch, but also revealed bidirectional gene flow between the two species via triploid interspecific hybrids. The populations showed continuous morphological variation connecting the species, but karyotypically they consisted of only three types of plants: diploids, triploids, and tetraploids. No aneuploids were found. Some of the tetraploid plants had B. pubescens morphology as expected, but most of them had intermediate characters. Most of the diploid plants were B. nana, but some were intermediates and a few had B. pubescens morphology. The triploid plants were either intermediates or they resembled one of the two species. Similar introgressive variation was observed among the diploid and triploid progeny of open-pollinated B. nana in a garden. Birch samples including field plants and artificial hybrids were further examined using a molecular method based on genomic Southern hybridization. The experiments verified introgression at the DNA level. PMID- 11773248 TI - The genetic basis of floral variation in Senecio jacobaea (Asteraceae). AB - The self-incompatible composite Senecio jacobaea (ragwort) exhibits geographic variation in the frequency of rayed and discoid (rayless) individuals. Hybrid progenies from within- and between-morph crosses were established in a seminatural (garden) environment to determine whether patterns of segregation conform to single-gene predictions (as found in other Senecio species), whether the direction of dominance is conducive to rapid evolutionary change in ray morphology, and whether geographically distant populations of the discoid morph utilize the same or different genes to suppress ray development. Data from segregating F2 and BC families were consistent with a genetic model involving one major locus and an unknown number of modifiers. Analysis of F1 progenies from different intermorph crosses using the same rayed plant as a seed parent revealed a variable and incomplete pattern of dominance, with a trend toward partial dominance in some crosses. Hybridizations between discoid populations produced a few rayed progeny (4%), but there was no tendency for the frequency of rayed progeny to increase with the geographic distance separating the parent populations. Results of this study indicate that major mutations have been important for the evolution of discoid populations of ragwort, that ray suppressing mutations should be directly available to selection in most populations, and that the suppression of rays is conditioned by the same or similar gene(s) in Atlantic and Baltic populations of the discoid taxon. PMID- 11773250 TI - Heritability of phenolics in Quercus laevis inferred using molecular markers. AB - Studies of quantitative inheritance of phenotypes do not generally encompass the range of environmental conditions to which a population may be exposed in a natural setting and are rarely conducted on long-lived species due to the time required for traditional crossing experiments. We used a marker-based method to estimate relatedness with microsatellite markers in a natural population of a long-lived oak, then used this inferred relatedness to examine quantitative genetic variation in the concentration of foliar phenolics. Estimating heritability using this method requires both significant relatedness and variance in relatedness over distance. However, this population did not show significant variance of relatedness, so only the presence of heritability, and its ranking among traits and environments, could be estimated. Seven foliar phenolics showed a significant relationship between phenotypic similarity and relatedness. The significance of this relationship varied among individual phenolic compounds, as well as by season. Genetic factors appeared to have a more measurable influence on the production of secondary compounds early in the season. After leaf expansion, covariance of relatedness and phenotypic variance appear to become less significant. Therefore heritability may vary seasonally for these traits. PMID- 11773249 TI - Breeding population size of a fragmented population of a Costa Rican dry forest tree species. AB - Pollen immigration can offset the effects of genetic drift and inbreeding in small populations. To understand the genetic consequences of forest fragmentation, estimates of pollen flow into remnant fragments are essential. Such estimates are straightforward for plants with singly sired, multiseeded fruits, since the pollen donor genotype for each fruit can be unambiguously reconstructed through full-sib genealogical analyses. Allozyme analyses were used to estimate pollen donor numbers from the progeny of fruits of the tropical dry forest tree Enterolobium cyclocarpum in a small (9.8 ha) fragmented population (N = 11) over three reproductive seasons (1994, 1995, and 1996). These analyses indicate that each tree receives pollen from many pollen donors. When data are pooled for the site, estimated maximum pollen donor pool sizes in all years exceed the number of individuals (56) in the 227 ha study area. Although unidentified pollen donors may be located as close as 250 m to the study trees, the number of unidentified pollen donors indicates that individuals in this forest fragment are part of a large network of reproductively active individuals. PMID- 11773251 TI - High levels of genetic polymorphism in the insular endemic herb Jepsonia malvifolia. AB - Jepsonia malvifolia is a long-lived perennial herb endemic to the Channel Islands of southern California and Guadalupe Island, Mexico. Twelve populations of J. malvifolia on San Clemente Island were surveyed for their genotype at 21 allozyme loci, revealing high levels of genetic polymorphism. For all individuals across San Clemente Island, 95.2% of loci are polymorphic with A(p) = 2.90 and H(e) = 0.179. Populations averaged 60.2% polymorphic loci with A(p) = 2.42 and H(e) = 0.158. Most variation is found within rather than among populations (G(ST) = 0.101), although differentiation among populations is significant. Genetic identities range from 0.936 to 0.999 with mean I = 0.975. There is no significant relationship between genetic and geographic distance. Gene flow among populations is Nm = 9.5 based on private alleles and Nm = 2.2 based on F(ST). Outcrossing rates based on fixation indices average t = 0.753, indicating a primarily outcrossed mating system. The genetic variation observed is unusually high for an insular endemic herb and indicates that J. malvifolia is unlikely to be endangered by genetic factors. PMID- 11773252 TI - Breed differences in allele frequency of the dopamine receptor D4 gene in dogs. AB - We previously reported that the dog dopamine receptor D4 (DRD4) gene is polymorphic as observed in humans, and four alleles were identified based on the number and/or order of the 12 and 39 bp sequences located in the homologous region of human DRD4. To assess the diversity of the DRD4 gene in dogs we examined the allelic variations in four breeds (beagle, golden retriever, Shetland sheepdog, and shiba) employing the polymerase chain reaction (PCR). As a result, we found three novel alleles and determined the DNA sequences of these alleles. The beagle shared four alleles, including 396, 435, 447a, and 447b, with the 435 (52.6%) and 447a (39.5%) alleles being common. The golden retriever had the 435 and 447a alleles, and the 435 allele was frequent (73.3%). In the Shetland sheepdog, the 435, 447a, and 498 alleles were observed, of which the 447a allele was most frequent (82.5%). The shiba had five alleles-447a, 447b, 486, 498, and 549-and the 447b allele was most common (55.4%). These findings suggest that the allele frequency varied among the four dog breeds, and analysis of the DRD4 polymorphism may therefore be useful for elucidating the relationships among dog breeds. PMID- 11773253 TI - Inheritance of a Lutescent-Leaf color trait in peanut. AB - A Lutescent-Leaf color mutant was recently found in the cultivated peanut (Arachis hypogaea L.). Crosses involving the Lutescent-Leaf mutant were made both between and within subspecies of hypogaea and fastigiata to determine its inheritance. The F1, F2, and F3 data indicated that two duplicate recessive genes, designated lut1 and lut2, control the Lutescent-Leaf color trait. No maternal or cytoplasmic effects were detected among progenies from reciprocal hybridization. PMID- 11773254 TI - Genetics of a new male-sterility locus in pigeonpea (Cajanus cajan [L.] Millsp.). AB - A natural male-sterile mutant was found in the population of a short-duration pigeonpea (Cajanus cajan[L.] Millsp.) cultivar ICPL 85010. This mutant is characterized by light yellow anthers of reduced size that are devoid of pollen grains. This mutant was crossed with two pigeonpea cultivars to study its inheritance. The F1, F2, and test cross data of the two crosses suggested that this male sterility trait is genetic in origin and is controlled by a single recessivegene. The F1 (mutant x ICPL 85010) plants were crossed with translucent (ms1) and arrowhead type (ms2) genetic male steriles reported earlier to study their allelic relationships. Segregation in the three-way cross F1 and F2 populations revealed that the mutant male-sterile gene was nonallelic to ms1 and ms2 loci and it is designated ms3. The new male sterility sources in pigeonpea will help in producing high-yielding hybrids and populations in diverse phenological groups. PMID- 11773255 TI - Susceptibility to spontaneous atherosclerosis in pigeons: an autosomal recessive trait. AB - The inheritance pattern for susceptibility to spontaneous (noninduced) aortic atherosclerosis in pigeons was determined by crossbreeding and backcrossing experiments with atherosclerosis-susceptible White Carneau and atherosclerosis resistant Show Racer breeds. Susceptibility, assessed by the presence of grossly visible lesions at the celiac bifurcation of the aorta at 3 years of age, demonstrated an inheritance pattern consistent with an autosomal recessive Mendelian trait. Cell culture studies indicated that susceptibility is a constitutive property of aortic cells as evidenced by vacuole formation and lipid content in smooth muscle cells from various tissues in susceptible pigeons. PMID- 11773257 TI - SGS--Spatial Genetic Software: a computer program for analysis of spatial genetic and phenotypic structures of individuals and populations. AB - We have developed a program called Spatial Genetic Software (SGS), which provides a user-friendly Windows tool to analyze both local and broad scale genetic and phenotypic structure. It can deal with nearly any type of genetic data, codominant (allozyme, PCR-RFLP, microsatellite) or dominant (RAPD, AFLP) markers, or biparentally (nuclear) or uniparentally (cpDNA and mtDNA) inherited markers. Data based on any of these markers can be analyzed, either as individual genotypes within a single population (local scale) or as allele or haplotype frequencies from different populations (broad scale). We also include a simple approach to analysis of spatial structure for continuous quantitative traits. The program implements various parameters to analyze spatial genetic and phenotypic structure: Moran's index, Geary's index, number of alleles in common, and approaches using genetic distances and F(ST) values. The statistical significance of all measures is verified by the use of a permutation test. The results are assessed by graphics that can be integrated, via the clipboard, to other Windows programs. The details of the computations are given in a table and can be stored as ASCII files. PMID- 11773256 TI - Mapping genes conferring resistance to Phytophthora root rot of soybean, Rps1a and Rps7. AB - A linkage map was constructed for two Phytophthora sojae Kauf. +Gerd. root rot resistance genes, Rps1a and Rps7, in soybean (Glycine max (L.) Merr.) using microsatellite or simple sequence repeat (SSR) markers. An F2 population consisting of 81 individuals derived from a cross between OX281, which carries Rps7, and Mukden, which carries Rps1a, was used as the mapping population. A linkage map consisting of 10 SSR markers was first constructed using the computer software MapMaker/EXP 3.0. Rps1a and Rps7 were then placed at two different loci in the same linkage group with LOD scores of 2.88 and 9.16, respectively. Rps1a and Rps7 were linked at a distance of 13.8 cM. Rps1a was flanked by Satt159 (0.7 cM) and Satt009 (3.2 cM). Rps7 was flanked by Satt009 (10.6 cM) and Satt125 (29.1 cM). PMID- 11773258 TI - Parallel computing in interval mapping of quantitative trait loci. AB - Linear regression analysis is considered the least computationally demanding method for mapping quantitative trait loci (QTL). However, simultaneous search for multiple QTL, the use of permutations to obtain empirical significance thresholds, and larger experimental studies significantly increase the computational demand. This report describes an easily implemented parallel algorithm, which significantly reduces the computing time in both QTL mapping and permutation testing. In the example provided, the analysis time was decreased to less than 15% of a single processor system by the use of 18 processors. We indicate how the efficiency of the analysis could be improved by distributing the computations more evenly to the processors and how other ways of distributing the data facilitate the use of more processors. The use of parallel computing in QTL mapping makes it possible to routinely use permutations to obtain empirical significance thresholds for multiple traits and multiple QTL models. It could also be of use to improve the computational efficiency of the more computationally demanding QTL analysis methods. PMID- 11773259 TI - Breast biopsy for mammographically detected non-palpable lesions using a vacuum assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit. AB - BACKGROUND: It is planned to start screening mammography throughout Japan in the near future. However, a minimally invasive biopsy procedure for mammographically detected non-palpable breast lesions is not available in almost all Japanese hospitals. It is crucial to develop a useful minimally invasive biopsy method which can be applied without difficulty. METHODS: Eighty-nine biopsies for 88 mammographically detected non-palpable breast lesions, consisting of 70 lesions with microcalcifications alone, eight masses without calcifications and 10 with both masses and microcalcifications, were performed using the combination of a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit. RESULTS: Microcalcifications were confirmed radiographically in the tissue obtained from 78 biopsies among 81 biopsies for the lesions with microcalcifications (96.3%). All the lesions without calcifications were considered to be biopsied successfully. Five patients complained of nausea or fainted during the localization or biopsy procedure and an additional patient suffered from hyperventilation syndrome. Five cases experienced mild subcutaneous bleeding in the breasts. CONCLUSIONS: The biopsy technique using the combination of a vacuum-assisted biopsy device and an upright-type stereotactic mammography unit is a cost-effective, safe and very useful method for mammographically detected non-palpable breast lesions. It is expected to be a standard method of biopsy for such lesions in many developed countries other than the USA. However, it is important to make the patients relaxed during the biopsy to prevent mental strain. PMID- 11773260 TI - Expression of the protein gene product 9.5, PGP9.5, is correlated with T-status in non-small cell lung cancer. AB - BACKGROUND: In a tumor, increased deubiquitination of cyclins by a protein gene product gene, PGP9.5, could contribute to the uncontrolled growth of somatic cells that is a hallmark of cancer. We hypothesized that PGP9.5 may be expressed in tumors of patients with non-small cell lung cancer (NSCLC). METHODS: Expression of PGP9.5 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 95 non-small cell lung carcinomas and adjacent histological normal lung samples. The data were analyzed with reference to clinicopathological factors. RESULTS: PGP9.5 transcripts were detected in 18 (12.8%) of the tumor samples, although some of paired normal lung samples showed very weak expression. There was no relationship between PGP9.5 gene expression and age, gender, N-status or pathological subtype. PGP9.5 gene was preferentially expressed in T3/T4 NSCLC (12/41, 29.3%) compared with T1/T2 NSCLC (6/54, 11.1%) (p = 0.0482). CONCLUSIONS: Although the PGP9.5 gene was not expressed in a majority of NSCLC tumors, we suggest that PGP9.5 may correlate with tumor invasion or progression of NSCLC. PMID- 11773261 TI - Treated natural history of superficial bladder cancer. AB - BACKGROUND: The present study was conducted to examine the natural history of superficial bladder cancer. METHODS: One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. RESULTS: The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. CONCLUSIONS: These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group. PMID- 11773262 TI - Toxicity and health-related quality of life during and after high dose rate brachytherapy followed by external beam radiotherapy for prostate cancer. AB - BACKGROUND: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. METHODS: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. RESULTS: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. CONCLUSIONS: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further. PMID- 11773263 TI - Four cases of meningeal hemangiopericytoma treated with surgery and radiotherapy. AB - We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation. PMID- 11773264 TI - A case with HER2-overexpressing breast cancer completely responded to humanized anti-HER2 monoclonal antibody. AB - This is a case report of a 57-year-old woman with a history of primary carcinoma of the right breast with metastases to the contralateral axillary lymph node. After a partial response (PR) was induced by high-dose chemotherapy with peripheral blood stem cell transplantation, she underwent mastectomy with biopsy of the bilateral axillary lymph nodes. Six months after surgery, the patient had multiple lung metastases. She was then treated with five cycles of fluorouracil, mitoxantrone and vindesine. Although a PR was achieved, further chemotherapy could not be given because of cardiac dysfunction. Since immunohistochemical staining for the HER2 gene product was strongly positive on the surface of primary tumor cells, humanized anti-HER2 monoclonal antibody (trastuzumab) was given intravenously. The metastatic lesion decreased in size and finally appeared to be only cicatricial. Twenty-one months after the initial administration of trastuzumab, the pulmonary lesion was excised. The pathological examination revealed no tumor cells in the resected specimen so further treatment was stopped. The relapse-free state has continued for 24 months after the pulmonary resection. PMID- 11773265 TI - Dermatofibrosarcoma protuberans metastasizing to cavernous sinuses and lungs: a case report. AB - Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low potential for distant metastases. We report a 22-year-old female patient with a typical cutaneous DFSP who developed five local recurrences followed by left cavernous sinus metastasis at the eighth year and right cavernous sinus and lung metastases at the ninth year. In each local recurrence the tumor showed histological signs of progression as being more cellular, having higher mitotic index and being aggressively invasive through the underlying soft tissues. The histopathological evaluation of the metastatic tumor resected from the left cavernous sinus revealed dedifferentiation from low-grade DFSP to higher grade fibrosarcomatous morphology. Immunohistochemical studies of the primary tumor and also the recurrent and metastatic tumors showed diffuse CD34 positivity in all specimens and p53 positivity was detected in the metastatic tumor resected from left cavernous sinus. PMID- 11773266 TI - Synchronous multifocal osteosarcoma with lymphatic spread in the lung: an autopsy case report. AB - Synchronous multifocal/multicentric osteosarcoma (MOS) is a rare variant of osteosarcoma. We report here an autopsy case of a 15-year-old boy with MOS. Radiological examinations showed multiple sclerotic lesions in the left distal femur and in the ipsilateral proximal tibia without pulmonary metastasis at the first examination. Histological examination showed osteoblastic-type osteosarcoma. Despite high-dose chemotherapy the patient died of multiple bone and lung involvements 6 months after the initial diagnosis. Autopsy examination revealed prominent invasion of the tumor cells into lymphatic vessels and pleural dissemination without the formation of bulky, nodular metastasis in the lungs. Metastases in pulmonary hilar lymph nodes were noted without metastasis in other organs. Immunohistochemistry revealed that p53 protein was positive in most of the tumor cells. In summary, the present case was characterized by multiple bone involvement and prominent lymphatic spread of sarcoma cells in the lungs. PMID- 11773268 TI - Prostate cancer in bone: importance of context for inhibition of matrix metalloproteinases. PMID- 11773270 TI - National Cancer Act: leaders reflect on 30 years of progress. PMID- 11773269 TI - Silence is golden: gene hypermethylation and survival in large-cell lymphoma. PMID- 11773274 TI - Heat shock protein vaccine: producing an immune response in mice and men. PMID- 11773276 TI - Is there less resistance on the chemoresistance front? PMID- 11773279 TI - Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. AB - BACKGROUND: The gene encoding the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers, including diffuse large B-cell lymphoma (B-DLCL). MGMT promoter hypermethylation is a favorable prognostic marker in patients with brain tumors treated with alkylating agents. METHODS: In a retrospective cohort study, we used methylation-specific polymerase chain reaction to analyze the MGMT promoter methylation status in tumor DNA of B-DLCL patients receiving cyclophosphamide as part of multidrug regimens. Molecular data were compared with patient response with the use of Student's t test. Disease free survival and overall survival were estimated by the Kaplan-Meier method and compared with the use of the log-rank test. Multivariable survival analyses were performed with the Cox proportional hazards model. All statistical tests were two sided. RESULTS: Thirty (36%) of 84 B-DLCL patients showed MGMT promoter hypermethylation in their lymphomas. The presence of MGMT methylation was associated with a statistically significant increase in overall survival (hazard ratio for time to death for nonmethylation versus methylation = 2.8; 95% confidence interval (CI) = 1.2 to 7.5; P =.01) and progression-free survival (hazard ratio for time to progression for nonmethylation versus methylation = 2.6; 95% CI = 1.3 to 5.8; P =.02). MGMT promoter hypermethylation was both independent of and stronger than established prognostic factors, such as age, disease stage, serum lactic dehydrogenase level, and performance status. CONCLUSION: MGMT promoter hypermethylation appears to be a useful marker for predicting survival in patients with B-DLCL treated with multidrug regimens including cyclophosphamide. PMID- 11773278 TI - Matrix metalloproteinase activity, bone matrix turnover, and tumor cell proliferation in prostate cancer bone metastasis. AB - BACKGROUND: The metastasis of prostate cancer to bone is associated with a substantial increase in bone matrix turnover. Matrix metalloproteinases (MMPs) play roles in both normal bone remodeling and invasion and metastasis of prostate cancer. This study was designed to determine the role of MMP activity in prostate cancer that has metastasized to bone. METHODS: Single human fetal bone fragments were implanted subcutaneously in immunodeficient mice. Four weeks later, PC3 human prostate cancer cells were injected directly into some of the implants, and daily treatment was begun with batimastat (a broad-spectrum MMP inhibitor). There were six mice (i.e., six implants) in each of four experimental arms: bone alone with and without batimastat and bone injected with PC3 cells with and without batimastat. Bone implants were harvested after 14 days of treatment and analyzed for MMP expression, bone histomorphometry, osteoclast counts, blood vessel density, and tumor cell proliferation and apoptosis. Complementary data were obtained from bone biopsy samples from patients and a bone organ coculture system. All statistical tests were two-sided. RESULTS: MMPs were detected in tumor and stromal cells of clinical specimens and experimental bone implants. In vivo, MMP inhibition reduced the number of osteoclasts per millimeter in PC3 injected implants-from 8.2 (95% confidence interval [CI] = 7.9 to 8.5) to 3.0 (95% CI = 2.3 to 3.7) (P =.006). In addition, it prevented degradation of marrow trabeculae within the bone implants (cross-sectional area of implant occupied by mineralized trabeculae: untreated implant = 29.1% [95% CI = 27.1% to 31.1%], PC3 injected implant = 14.0% [95% CI = 10.9% to 17.1%] [P =.005 versus untreated], and batimastat-treated PC3-injected implant = 27.2% [95% CI = 22.4% to 32.0%] [P =.03 versus PC3 injected alone]). MMP inhibition reduced proliferating tumor cells from 20.8% (95% CI = 19.9% to 21.7%) to 7.4% (95% CI = 5.2% to 9.6%) (P =.006), without affecting angiogenesis or apoptosis. In vitro, MMP inhibition had no toxic effect on PC3 cells but prevented calcium release from bone fragments cocultured with PC3 cells. CONCLUSIONS: MMP activity appears to play an important role in bone matrix turnover when prostate cancer cells are present in bone. Bone matrix turnover and metastatic tumor growth appear to be involved in a mutually supportive cycle that is disrupted by MMP inhibition. PMID- 11773280 TI - Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. AB - BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of developing ovarian cancer, but the mechanism for the risk reduction has not been well defined. In this study, we investigate the relationship between the progestin and estrogen potency in combination OCs and the risk of developing ovarian cancer. METHODS: The study included 390 case subjects with epithelial ovarian cancer and 2865 control subjects, between 20 and 54 years of age, identified from the Cancer and Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between ovarian cancer risk and combination OC formulations while controlling for potential confounders. All statistical tests were two-sided. RESULTS: With users of high-progestin/high-estrogen potency OC as the referent group, users of low-progestin/high-estrogen potency formulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogen potency formulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higher risk of ovarian cancer than users of high-progestin/high-estrogen potency formulation. Low-progestin potency OC formulations were associated with a statistically significant higher risk than high-progestin potency formulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration. CONCLUSION: The combination OC formulations with high-progestin potency appear to be associated with a greater reduction in ovarian cancer risk than those with low-progestin potency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of the progestin. PMID- 11773281 TI - Quality of life in long-term, disease-free survivors of breast cancer: a follow up study. AB - BACKGROUND: Women with breast cancer are the largest group of female survivors of cancer. There is limited information about the long-term quality of life (QOL) in disease-free breast cancer survivors. METHODS: Letters of invitation were mailed to 1336 breast cancer survivors who had participated in an earlier survey and now were between 5 and 10 years after their initial diagnosis. The 914 respondents interested in participating were then sent a survey booklet that assessed a broad range of QOL and survivorship concerns. All P values were two-sided. RESULTS: A total of 817 women completed the follow-up survey (61% response rate), and the 763 disease-free survivors in that group, who had been diagnosed an average of 6.3 years earlier, are the focus of this article. Physical well-being and emotional well-being were excellent; the minimal changes between the baseline and follow-up assessments reflected expected age-related changes. Energy level and social functioning were unchanged. Hot flashes, night sweats, vaginal discharge, and breast sensitivity were less frequent. Symptoms of vaginal dryness and urinary incontinence were increased. Sexual activity with a partner declined statistically significantly between the two assessments (from 65% to 55%, P =.001). Survivors with no past systemic adjuvant therapy had a better QOL than those who had received systemic adjuvant therapy (chemotherapy, tamoxifen, or both together) (physical functioning, P =.003; physical role function, P =.02; bodily pain, P =.01; social functioning, P =.02; and general health, P =.03). In a multivariate analysis, past chemotherapy was a statistically significant predictor of a poorer current QOL (P =.003). CONCLUSIONS: Long-term, disease-free breast cancer survivors reported high levels of functioning and QOL many years after primary treatment. However, past systemic adjuvant treatment was associated with poorer functioning on several dimensions of QOL. This information may be useful to patients and physicians who are engaging in discussion of the risks and benefits of systemic adjuvant therapy. PMID- 11773282 TI - Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta. AB - BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P Ca(2+) (0.87). The I(mtx) activation time course reflected the changes in intracellular Ca(2+) and Na(+) measured with the fluorescent indicators fura-2 and SBFI, respectively, suggesting that the activation of I(mtx) brings about an increment in intracellular Ca(2+) and Na(+). Reducing the extracellular Ca(2+) concentration below 1.8 mM prevented the activation of I(mtx) and the increment in intracellular Na(+) induced by MTX. Mn(2+) and Mg(2+) could not replace Ca(2+), but Ba(2+) could replace Ca(2+). MTX activation of current in 10 mM Ba(2+) was approximately 50 % of that induced in the presence of 1.8 mM Ca(2+). When 5 mM of the Ca(2+) chelator BAPTA was included in the patch pipette, MTX either failed to activate the current or induced a small current (less than 15 % of the control), indicating that intracellular Ca(2+) is also required for the activation of I(mtx). Intracellular Ba(2+) can replace Ca(2+) as an activator of I(mtx). However, in the presence of 10 mM Ba(2+) the activation by MTX of the current was 50 % less than the activation with nM concentrations of free intracellular Ca(2+). PMID- 11773319 TI - Acute synaptic modulation by nicotinic agonists in developing cerebellar Purkinje cells of the rat. AB - The synaptic properties of the immature mammalian cerebellum were studied with a focus on the nicotinic modulation of synaptic transmission. Synaptic currents in Purkinje neurones were recorded using whole-cell patch electrodes applied to cerebellar slices (200 microm thick) obtained from newborn rats at postnatal days 5-10 (P5-P10). When the membrane potential of a Purkinje cell was held at -40 mV, spontaneous synaptic currents occurring in the cell comprised both inward and outward components. The former was glutamatergic and the latter was GABAergic, as confirmed by measuring reversal potentials and by using the specific glutamate and GABA blockers, 6-cyano-7-nitroquinoziline-2,3-dione and bicuculline, respectively. Application of ACh (0.1-1000 microM) from a 'Y tube' enhanced the occurrence of both glutamatergic and GABAergic synaptic currents in Purkinje cells. These responses appeared within 1 s after the application of ACh, and they were mimicked by nicotinic agonists (10 microM nicotine, 10 microM cytisine, 10 microM 1,1-dimethyl-4-phenyl-piperazinium iodide, or 10 nM epibatidine), but were sensitive to a specific nicotinic antagonist (1 microM dihydro-beta erythroidine). When the generation of action potentials by cerebellar neurones in the slice preparation was blocked by the addition of TTX (1 microM) to the external saline, these ACh-induced responses almost disappeared. This indicates that the enhanced synaptic activities in Purkinje cells are induced via presynaptic nicotinic receptors on the excitatory and inhibitory interneurones, presumably on the proximal axons or somatodendritic domains of granule cells and basket cells in the cerebellar cortex. Interestingly, these nicotinic effects were remarkable in immature rats (P5-P10), but were barely detectable in older rats (more than 10 days of age), indicating that nicotinic ACh receptors are regulated developmentally and may play a novel role in the maturing cerebellum. PMID- 11773320 TI - Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A. AB - The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade. PMID- 11773321 TI - Fatty acid signalling in a mouse enteroendocrine cell line involves fatty acid aggregates rather than free fatty acids. AB - Fatty acids induce cholecystokinin (CCK) secretion both in humans and from murine enteroendocrine cell lines. In both cases, only fatty acids above a critical acyl chain length (C(10)) are capable of inducing a response. Using the enteroendocrine cell line STC-1, the aim of this study was to determine whether this acyl chain length dependency is related to the fact that longer chain fatty acids are relatively insoluble in aqueous solutions and, if so, whether it is insoluble aggregates of fatty acids rather than free fatty acids which evoke CCK secretion. Solutions of fatty acids (chain length C(8)-C(14)), which were judged by filtration and Zeta sizer measurement to contain no fatty acid aggregates, never evoked CCK secretion from STC-1 cells. Filtering fatty acid solutions (of chain length C(10), C(12) and C(14)) through polytetrafluoroethylene (PTFE) filters (0.45 microm pore size) revealed a narrow concentration range for each acid over which the amount of fatty acid removed from the solution increased sharply due to the formation of fatty acid aggregates. Filtration experiments, in which suspensions of C(10), C(12) and C(14) fatty acids were passed through pore sizes of 0.2, 0.45 or 1.2 microm, suggested that STC-1 cells did not respond to fatty acid aggregates of greater than 1.2 microm, while at least 50 % of the CCK response was mediated by aggregates which were smaller than 0.45 microm. Fatty acids induce CCK secretion from STC-1 cells by elevating intracellular Ca(2+) concentration ([Ca(2+)](i)). We therefore measured the effects on [Ca(2+)](i) of filtered C(10), C(12) and C(14) fatty acids. In all cases, [Ca(2+)](i) responses were closely correlated with CCK secretion. Interestingly, while filtrates of fatty acid solutions evoked CCK secretion and elevated [Ca(2+)](i), freshly prepared solutions of fatty acids at the same concentration as the filtrates did not. This suggested that fatty acid aggregates were not in equilibrium with the solvent after filtration. The observation that the ability of C(10), C(12) and C(14) filtrates to elevate [Ca(2+)](i) decayed with time was consistent with this hypothesis. Furthermore, sonication of the filtrates abolished their ability to elevate [Ca(2+)](i). These data further suggest that it is a physical property of the fatty acid solution (the presence of insoluble fatty aggregates) which is responsible for the observed cellular responses. We conclude that Ca(2+) mobilisation and CCK secretion in STC-1 cells is driven by a signal transduction mechanism that senses insoluble fatty acid aggregates, rather than free fatty acids in solution. PMID- 11773322 TI - Relaxation by vasoactive intestinal polypeptide in the gastric fundus of nitric oxide synthase-deficient mice. AB - In many gastrointestinal tissues nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) both play a role as inhibitory non-adrenergic non-cholinergic neurotransmitters. As the mode of interaction between NO and VIP remains controversial, the aim of this study was to investigate the interplay between NO and VIP in the mouse gastric fundus and to evaluate the nitric oxide synthase (NOS) isoform involved in VIP-induced relaxation by using inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) knockout mice. The influence of NOS inhibitors on the relaxant effect of VIP was determined in isolated smooth muscle cells and smooth muscle strips of wild-type and knockout mice. In isolated smooth muscle cells from wild-type, eNOS knockout and nNOS knockout mice, the relaxation induced by VIP (10(-9) M) was inhibited by approximately 70-95 % by both the non-selective NOS inhibitor N(G)-nitro-L-arginine (L-NA; 10(-4) M) and the selective inducible NOS inhibitor N-(3-(aminomethyl)-benzyl)acetamidine (1400W; 10(-6) M). In cells isolated from iNOS knockout mice, VIP still induced full relaxation but it was not influenced by L-NA or 1400W. In smooth muscle strips from wild-type and knockout mice, the concentration-dependent relaxation by VIP (10(-9) to 3 x 10(-7) M) was not influenced by L-NA or 1400W. These results suggest that the experimental method determines the influence of NOS inhibitors on the relaxant effect of VIP. iNOS, probably induced by the isolation procedure, might be involved in the relaxant effect of VIP in isolated smooth muscle cells but not in classic smooth muscle strips. PMID- 11773323 TI - Regulation of pacemaker frequency in the murine gastric antrum. AB - PGE(2) has been linked to the production of gastric arrhythmias such as tachygastria. The interstitial cells of Cajal (ICC) generate electrical rhythmicity in gastrointestinal muscles, and may therefore be a target for PGE(2) in gastric muscles. We cultured ICC from the murine gastric antrum, verified that cells were Kit immunoreactive, and measured spontaneous slow waves. These events were caused by spontaneous inward (pacemaker) currents that were not blocked by nifedipine. Forskolin and 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP) reduced the frequency of pacemaker currents in ICC and of slow waves in intact antral muscles. The effects of forskolin and 8-Br-cAMP were not blocked by inhibitors of protein kinase A, suggesting that cAMP has direct effects on pacemaker activity. PGE(2) mimicked the effects of forskolin and 8-Br-cAMP on ICC, but increased slow-wave frequency in intact muscles. Therefore, the chronotropic effects of specific prostaglandin EP receptor agonists were examined. Butaprost and ONO-AE1-329, EP(2) and EP(4) receptor agonists, mimicked the effects of forskolin and 8-Br-cAMP on ICC and intact muscles. Sulprostone (EP(3)>EP(1) agonist), GR63799, and ONO-AE-248 (EP(3) agonists) enhanced the frequencies of pacemaker currents in ICC and slow waves in intact muscles. The effects of sulprostone were not blocked by SC-19220, an EP(1) receptor antagonist. These observations suggest that the positive chronotropic effects of PGE(2) in intact muscles are mediated by EP(3) receptor stimulation. The effects of PGE(2) in intact muscles may be dependent upon the relative expression of EP receptors and/or proximity of receptors to sources of PGE(2). PMID- 11773324 TI - Differential effect of angiotensin II on blood circulation in the renal medulla and cortex of anaesthetised rats. AB - The renal medulla is sensitive to hypoxia, and a depression of medullary circulation, e.g. in response to angiotensin II (Ang II), could endanger the function of this zone. Earlier data on Ang II effects on medullary vasculature were contradictory. The effects of Ang II on total renal blood flow (RBF), and cortical and medullary blood flow (CBF and MBF: by laser-Doppler flux) were studied in anaesthetised rats. Ang II infusion (30 ng kg(-1) min(-1) i.v.) decreased RBF 27 +/- 2 % (mean +/- S.E.M.), whereas MBF increased 12 +/- 2 % (both P < 0.001). Non-selective blockade of Ang II receptors with saralasin (3 microg kg(-1) min(-1) i.v.) increased RBF 12 +/- 2 % and decreased MBF 8 +/- 2 % (P < 0.001). Blockade of AT(1) receptors with losartan (10 mg kg(-1)) increased CBF 10 +/- 2 % (P < 0.002) and did not change MBF. Losartan given during Ang II infusion significantly increased RBF (53 +/- 7 %) and decreased MBF (27 +/- 7 %). Blockade of AT(2) receptors with PD 123319 (50 microg kg(-1) min(-1) i.v.) did not change CBF or MBF. Intramedullary infusion of PD 123319 (10 microg min(-1)) superimposed on intravenous Ang II infusion did not change RBF, but slightly decreased MBF (4 +/- 2 %, P < 0.05). We conclude that in anaesthetised surgically prepared rats, exogenous or endogenous Ang II may not depress medullary circulation. In contrast to the usual vasoconstriction in the cortex, vasodilatation was observed, possibly related to secondary activation of vasodilator paracrine agents rather than to a direct action via AT(2) receptors. PMID- 11773325 TI - Role of angiotensin II in dynamic renal blood flow autoregulation of the conscious dog. AB - The influence of angiotensin II (ANGII) on the dynamic characteristics of renal blood flow (RBF) was studied in conscious dogs by testing the response to a step increase in renal artery pressure (RAP) after a 60 s period of pressure reduction (to 50 mmHg) and by calculating the transfer function between physiological fluctuations in RAP and RBF. During the RAP reduction, renal vascular resistance (RVR) decreased and upon rapid restoration of RAP, RVR returned to baseline with a characteristic time course: within the first 10 s, RVR rose rapidly by 40 % of the initial change (first response, myogenic response). A second rise began after 20-30 s and reached baseline after an overshoot at 40 s (second response, tubuloglomerular feedback (TGF)). Between both responses, RVR rose very slowly (plateau). The transfer function had a low gain below 0.01 Hz (high autoregulatory efficiency) and two corner frequencies at 0.026 Hz (TGF) and at 0.12 Hz (myogenic response). Inhibition of angiotensin converting enzyme (ACE) lowered baseline RVR, but not the minimum RVR at the end of the RAP reduction (autoregulation-independent RVR). Both the first and second response were reduced, but the normalised level of the plateau (balance between myogenic response, TGF and possible slower mechanisms) and the transfer gain below 0.01 Hz were not affected. Infusion of ANGII after ramipril raised baseline RVR above the control condition. The first and second response and the transfer gain at both corner frequencies were slightly augmented, but the normalised level of the plateau was not affected. It is concluded that alterations of plasma ANGII within a physiological range do not modulate the relative contribution of the myogenic response to the overall short-term autoregulation of RBF. Consequently, it appears that ANGII augments not only TGF, but also the myogenic response. PMID- 11773326 TI - Direct and indirect modulation of rat cardiac sarcoplasmic reticulum function by n-3 polyunsaturated fatty acids. AB - Measurements were made of trans-sarcolemmal Ca(2+) fluxes and intracellular [Ca(2+)](i) in rat ventricular myocytes loaded with Indo-1 to determine how the n 3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) suppresses spontaneous waves of Ca(2+) release. We report that in 10 microM EPA, the Ca(2+) efflux generated by individual waves increased by 11.3 +/- 4.9 % over control levels. However, wave-generated efflux per unit time fell overall by 19 +/- 5.3 %. On removal of EPA, wave frequency increased transiently such that Ca(2+) efflux was greater than normal and the cell lost 28.0 +/- 10.6 micromol l(-1) Ca(2+). This probably represents the loss of extra Ca(2+) accumulated by the sarcoplasmic reticulum (SR), while Ca(2+) release was inhibited. These results are evidence of inhibition of the SR Ca(2+)-release mechanism and reduced availability of Ca(2+) to the SR. From the relationship between average intracellular Ca(2+) and the frequency of spontaneous waves, we have calculated the relative contributions of these different mechanisms to the lower frequency of waves. In EPA, the frequency of spontaneous waves fell by 37.5 +/- 8.1 %, the majority of this (29.2 +/- 8.8 %) is due to inhibition of the Ca(2+)-release mechanism. In EPA, the rate of fall of Ca(2+) in the caffeine response (an indicator of surface membrane Ca(2+) efflux pathway activity) was not altered. We conclude, therefore, that the lower resting level of Ca(2+) observed in EPA is due to a lower influx of Ca(2+) across the surface membrane rather than increased activation of efflux pathways. How these effects might contribute to the anti-arrhythmic actions of EPA is discussed. PMID- 11773327 TI - Effect of taurine on sarcoplasmic reticulum function and force in skinned fast twitch skeletal muscle fibres of the rat. AB - We examined the effect of taurine on depolarisation-induced force responses and sarcoplasmic reticulum (SR) function in mechanically skinned skeletal muscle fibres from the extensor digitorum longus (EDL) of the rat. Taurine (20 mM) produced a small but significant (P < 0.01) decrease in the sensitivity of the contractile apparatus to Ca(2+) (increase in the [Ca(2+)] corresponding to 50 % of maximum force of about 7 %; n = 10) and in maximum force (92.0 +/- 1.0 % of controls) in the skinned fibres. Taurine had no statistically significant effect on the slope of the force-pCa curve. Depolarisation-induced force responses in the skinned fibres were markedly increased in peak value by 20 mM taurine, to 120.8 +/- 5.3 % of control measurements (P = 0.0006, n = 27). Taurine (20 mM) significantly increased the SR Ca(2+) accumulation in the skinned fibres by 34.6 +/- 9.3 % compared to control conditions (measured by comparing the integral of caffeine contractures in fibres previously loaded with Ca(2+) in the absence or presence of taurine; P = 0.0014, n = 10). Taurine (20 mM) also increased both the peak and rate of rise of caffeine-induced force responses in the fibres by 29.2 +/- 9.7 % (P = 0.0298, n = 6) and 27.6 +/- 8.9 % (P = 0.037), respectively, compared with controls. This study shows that taurine is a modulator of contractile function in mammalian skeletal muscle. Taurine may increase the size of depolarisation-induced force responses by augmenting SR Ca(2+) accumulation and release. PMID- 11773329 TI - Effect of eccentric muscle contractions on Golgi tendon organ responses to passive and active tension in the cat. AB - To investigate the possibility of a peripheral contribution to the perturbations of force sensation reported to occur after eccentric exercise, responses to passive and active tension were recorded from Golgi tendon organs in the medial gastrocnemius muscle of the anaesthetised cat, before and after a series of eccentric contractions. After the eccentric contractions, nearly all tendon organs commenced firing at a shorter muscle length during slow passive stretch than before, probably because of a rise in whole muscle passive tension. There was a small drop in the sensitivity to incremental tension, but no mean change in tension threshold. Following the eccentric contractions, there was a small, but not significant, increase in tendon organ sensitivity to active tension, which was graded using a method of optimised, distributed stimulation of divided ventral roots. Sensitivity was estimated as the mean response over a range of tensions and as the change in discharge rate in response to incremental tension. The experiments provided the opportunity of comparing tendon organ sensitivities to graded passive and active whole muscle tension. In agreement with previous work in which whole muscle nerve stimulation was employed, little difference was found. It was concluded that the peripheral contribution to perturbations of force perception after eccentric exercise is likely to be small and that the centrally derived sense of effort plays the dominant role. Tendon organs appear to be remarkably reliable in signalling whole muscle tension, whether passive or active, and even after the muscle's force production has been disturbed by fatigue or eccentric exercise. PMID- 11773328 TI - Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate. AB - The aim of the present study was to determine whether the activation of the pyruvate dehydrogenase complex (PDC) by dichloroacetate (DCA) is associated with faster O(2) uptake (V(O2)) on-kinetics. V(O2) on-kinetics was determined in isolated canine gastrocnemius muscles in situ (n = 6) during the transition from rest to 4 min of electrically stimulated isometric tetanic contractions, corresponding to approximately 60-70 % of peak V(O2). Two conditions were compared: (1) control (saline infusion, C); and (2) DCA infusion (300 mg (kg body mass)(-1), 45 min before contraction). Muscle blood flow (Q) was measured continuously in the popliteal vein; arterial and popliteal vein O(2) contents were measured at rest and at 5-7 s intervals during the transition. Muscle V(O2) was calculated as Q multiplied by the arteriovenous O(2) content difference. Muscle biopsies were taken before and at the end of contraction for determination of muscle metabolite concentrations. DCA activated PDC at rest, as shown by the 9 fold higher acetylcarnitine concentration in DCA (vs. C; P < 0.0001). Phosphocreatine degradation and muscle lactate accumulation were not significantly different between C and DCA. DCA was associated with significantly less muscle fatigue. Resting and steady-state V(O2) values during contraction were not significantly different between C and DCA. The time to reach 63 % of the V(O2) difference between the resting baseline and the steady-state V(O2) values during contraction was 22.3 +/- 0.5 s in C and 24.5 +/- 1.4 s in DCA (n.s.). In this experimental model, activation of PDC by DCA resulted in a stockpiling of acetyl groups at rest and less muscle fatigue, but it did not affect 'anaerobic' energy provision and V(O2) on-kinetics. PMID- 11773330 TI - Effects of resistance and stretching training programmes on the viscoelastic properties of human tendon structures in vivo. AB - The present study examined whether resistance and stretching training programmes altered the viscoelastic properties of human tendon structures in vivo. Eight subjects completed 8 weeks (4 days per week) of resistance training which consisted of unilateral plantar flexion at 70 % of one repetition maximum with 10 repetitions per set (5 sets per day). They performed resistance training (RT) on one side and resistance training and static stretching training (RST; 10 min per day, 7 days per week) on the other side. Before and after training, the elongation of the tendon structures in the medial gastrocnemius muscle was directly measured using ultrasonography, while the subjects performed ramp isometric plantar flexion up to the voluntary maximum, followed by a ramp relaxation. The relationship between estimated muscle force (F(m)) and tendon elongation (L) was fitted to a linear regression, the slope of which was defined as stiffness. The hysteresis was calculated as the ratio of the area within the F(m)-L loop to the area beneath the load portion of the curve. The stiffness increased significantly by 18.8 +/- 10.4 % for RT and 15.3 +/- 9.3 % for RST. There was no significant difference in the relative increase of stiffness between RT and RST. The hysteresis, on the other hand, decreased 17 +/- 20 % for RST, but was unchanged for RT. These results suggested that the resistance training increased the stiffness of tendon structures as well as muscle strength and size, and the stretching training affected the viscosity of tendon structures but not the elasticity. PMID- 11773331 TI - Modulation of network behaviour by changes in variance in interneuronal properties. AB - Interneurones are important regulators of neuronal networks. The conventional approach to interneurones is to focus on the mean values of various parameters. Here we tested the hypothesis that changes in the variance of interneuronal properties (e.g. in the degree of scattering of parameter values of individual cells around the population mean) may modify the behaviour of networks. Biophysically based multicompartmental models of principal cells and interneurones showed that changes in the variance in the electrophysiological and anatomical properties of interneurones significantly alter the input-output functions, rhythmicity and synchrony of principal cells, even if the mean values were unchanged. In most cases, increased heterogeneity in interneurones resulted in stronger inhibition of principal cell firing; however, there were parameter ranges where increased interneuronal variance decreased the inhibition of principal cells. Electrophysiological recordings showed that the variance in the resting membrane potential of CA1 stratum oriens interneurones persistently increased following experimental complex febrile seizures in developing rats, without a change in the mean resting membrane potential, indicating that lasting alterations in interneuronal heterogeneity can take place in real neuronal systems. These computational and experimental data demonstrate that modifications in interneuronal population variance influence the behaviour of neuronal networks, and suggest a physiological role for interneuronal diversity. Furthermore, the results indicate that interneuronal heterogeneity can change in neurological diseases, and raise the possibility that neuromodulators may act by regulating the variance of key parameters in interneuronal populations. PMID- 11773332 TI - Mechanisms of intracortical I-wave facilitation elicited with paired-pulse magnetic stimulation in humans. AB - In order to elucidate the mechanisms underlying intracortical I-wave facilitation elicited by paired-pulse magnetic stimulation, we compared intracortical facilitation of I1-waves with that of I3-waves using single motor unit and surface electromyographic (EMG) recordings from the first dorsal interosseous muscle (FDI). We used a suprathreshold first stimulus (S1) and a subthreshold second stimulus (S2). In most experiments, both stimuli induced currents in the same direction. In others, S1 induced posteriorly directed currents and S2 induced anteriorly directed currents. When both stimuli induced anteriorly directed currents (I1-wave effects), an interstimulus interval (ISI) of 1.5 ms resulted in extra facilitation of the responses to S1 alone. The latency of this effect was equivalent to that of the I2-wave from S1. When S1 evoked posteriorly directed currents (I3-wave recruitment), facilitation occurred at a latency corresponding to the I3-wave from S1. This facilitation occurred at an ISI of 1.5 ms when both S1 and S2 flowed posteriorly, and at an ISI of approximately 3.5 ms when S1 was posteriorly and S2 was anteriorly directed. Based on these findings, we propose the following mechanisms for intracortical I-wave facilitation. When S1 and S2 induce currents in the same direction, facilitation is produced by summation between excitatory postsynaptic potentials (EPSPs) elicited by S1 and subliminal depolarization of interneurones elicited by S2 directly. When S1 and S2 induce currents in the opposite direction, facilitation is produced by the same mechanism as above or by temporal and spatial summation of EPSPs elicited by two successive stimuli at interneurones or corticospinal neurones of the motor cortex. PMID- 11773333 TI - Spontaneous arousal activity in infants during NREM and REM sleep. AB - The infant arousal response involves subcortical and cortical responses occurring as a sequence of stereotyped behaviour regardless of the eliciting stimulus. The spontaneous activity of these responses during sleep, however, is uncertain. We examined the spontaneous arousal pattern in normal infants to determine the sequence of responses, and to examine their periodicity and the effects of sleep state. We performed a nap polysomnographic study on 10 normal infants between 2 and 10 weeks of age. Electroencephalographic and electro-oculographic activity, and respiratory airflow and movements were measured, and video recordings were made throughout each study. Different levels of arousal behaviour were examined. We found that spontaneous arousal activity occurred frequently and the majority of responses occurred as a sequence involving an augmented breath followed by a startle and then cortical arousal. Subcortical arousals as reflected by augmented breaths and startles were more common than cortical arousals. Additionally, augmented breaths followed by apnoea were recorded and were not usually associated with other arousal responses. All of the responses occurred periodically either as bursts of activity or as isolated responses. Each of the responses occurred more frequently during rapid eye movement (REM) sleep than during non-rapid eye movement (NREM) sleep. We conclude that there is an endogenous rhythm of spontaneous activity in infants involving excitatory processes from the brainstem, which may or may not be closely followed by cortical excitation. The spontaneous arousal responses occur periodically but with a high level of irregularity and the level of activity is affected by sleep state. PMID- 11773334 TI - Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy. AB - Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 +/- 32.6 vs. 9.8 +/- 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 +/- 0.60 vs. 2.07 +/- 1.04 mmHg BBI(-1) (BBI, beat to-beat interval), P < 0.05), as was HR-TS (8.46 +/- 7.90 vs. 30.73 +/- 22.90 ms BBI(-1), P < 0.01). HR-TO was significantly higher in IDC patients (-0.56 +/- 2.19 vs. -5.52 +/- 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC. PMID- 11773335 TI - Cortically evoked neural volleys to the human hand are increased during ischaemic block of the forearm. AB - Reorganisation of the motor cortex may occur after limb amputation or spinal cord injury. In humans, transcranial magnetic stimulation (TMS) shows expansion of motor cortical representations of muscles proximal to the injury. Similarly, ischaemic block of the hand can increase acutely the representation of the biceps muscle, measured by increased biceps motor potentials evoked by TMS. It is thought that this increase occurs at the expense of the cortical representation of the paralysed and deafferented hand muscles but this has never been investigated. To study what changes occur in the cortical representation of the hand muscles during ischaemic block, a tungsten microelectrode was inserted into the ulnar or median nerve above the elbow and the size of the neural potential elicited by TMS in fascicles supplying the hand was measured in seven subjects. Prior to ischaemia, TMS evoked EMG responses in the intrinsic hand muscles. In the nerve, a brief motor potential preceded the response in the muscle and was followed by a contraction-induced sensory potential. During 40 min of ischaemia produced by a blood pressure cuff inflated around the forearm to 210 mmHg, the EMG response to TMS and the sensory potential from the hand were progressively blocked. However, the motor neural evoked potential showed a significant increase in amplitude during the ischaemic period (30.5 %, P = 0.005). The increase in the neural potential suggests that output to the hand evoked from the cortex by TMS was not decreased by ischaemic block. Thus, we conclude that the increased response of biceps to TMS during distal ischaemia is not accompanied by a corresponding decrease in the motor cortical representation of the hand. PMID- 11773336 TI - Sustained contractions produced by plateau-like behaviour in human motoneurones. AB - Electrical stimulation over human muscle can generate force directly by activation of motor axons and indirectly by 'reflex' recruitment of spinal motoneurones. These experiments were designed to define the properties of the centrally generated 'reflex' force, including the optimal stimulus conditions for producing it in tibialis anterior (TA) and triceps surae (TS), and its interaction with volition. Subjects (n = 21) were seated with their foot strapped to an isometric myograph. Surface EMG was recorded from TS and TA. High-frequency electrical stimulation (100 Hz) of TS and TA with wide pulse widths (1 ms) was most effective to evoke the sustained centrally generated forces. The maximal force evoked by this mechanism during stimulation of TA for 40 s was approximately 42 % of that produced by a maximal voluntary contraction. For both muscle groups, ramp increases and decreases in stimulus frequency (from approximately 4 to 100 Hz and back to 4 Hz over 6 s) resulted in marked hysteresis in the force-frequency plot. After a single 'burst' of 100 Hz stimulation during prolonged stimulation at 25 Hz, force remained elevated. Repeated bursts often generated progressively larger force increments. These behaviours were abolished by an anaesthetic nerve block proximal to the stimulation site, confirming the central origin for the 'extra' force. After a brief voluntary contraction was performed during 25 Hz stimulation, force remained elevated, and this showed some gradation with voluntary contraction amplitude. Sometimes voluntary contractions alone initiated the sustained central motor output. Involuntary contractions often persisted for many seconds after electrical stimulation ceased. These were not terminated by brief inhibitory inputs to the active motoneurones but could be stopped by the voluntary command to 'relax completely'. Overall, these centrally generated contractions are consistent with activation of plateau potentials in motoneurones innervating the ankle dorsiflexors and plantarflexors. Large forces can be produced through this mechanism. The interaction with volitional drives suggests that plateau behaviour may contribute significantly to the normal output of human motoneurones. PMID- 11773337 TI - Limb neurovascular control during altered otolithic input in humans. AB - Head-down rotation (HDR), which activates the vestibulosympathetic reflex, increases leg muscle sympathetic nerve activity (MSNA) and produces calf vasoconstriction with no change in either cardiac output or arterial blood pressure. Based on animal studies, it was hypothesized that differential control of arm and leg MSNA explains why HDR does not alter arterial blood pressure. Fifteen healthy subjects were studied. Heart rate, arterial blood pressure, forearm and calf blood flow, and leg MSNA responses were measured during HDR in these subjects. Simultaneous recordings of arm and leg MSNA were obtained from five of the subjects. Forearm and calf blood flow, vascular conductances, and vascular resistances were similar before HDR, as were arm and leg MSNA. HDR elicited similar significant increases in leg (Delta 6 +/- 1 bursts min(-1); 59 +/- 16 % from baseline) and arm MSNA (Delta 5 +/- 1 bursts min(-1); 80 +/- 28 % from baseline). HDR significantly decreased calf (-19 +/- 2 %) and forearm vascular conductance (-12 +/- 2 %) and significantly increased calf (25 +/- 4 %) and forearm vascular resistance (15 +/- 2 %), with ~60 % greater vasoconstriction in the calf than in the forearm. Arterial blood pressure and heart rate were not altered by HDR. These results indicate that there is no differential control of MSNA in the arm and leg during altered feedback from the otolith organs in humans, but that greater vasoconstriction occurs in the calf than in the forearm. These findings indicate that vasodilatation occurs in other vascular bed(s) to account for the lack of increase in arterial blood pressure during HDR. PMID- 11773338 TI - Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre. AB - When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain. PMID- 11773339 TI - Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. AB - Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio-acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (+/- S.E.M.) heart rates before lower body suction were similar pre-flight and in flight. Heart rate responses to -30 mmHg were greater in flight (from 56 +/- 4 to 72 +/- 4 beats min(-1)) than pre-flight (from 56 +/- 4 at rest to 62 +/- 4 beats min(-1), P < 0.05). Noradrenaline spillover and clearance were increased from pre-flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post-flight days 1 or 2 (n = 5, P < 0.05). In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre-flight levels or higher in each subject (35 pre-flight vs. 40 bursts min(-1) in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic responses to lower body suction are exaggerated. Therefore, notwithstanding hypovolaemia, astronauts respond normally to simulated orthostatic stress and are able to maintain their arterial pressures at normal levels. PMID- 11773341 TI - Foot and mouth disease control: the next steps. PMID- 11773340 TI - Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight. AB - Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal. PMID- 11773342 TI - Freedom fighters and rebels: the rules of civil war. PMID- 11773344 TI - Rabies in North America and Europe. PMID- 11773343 TI - Stem cells for all seasons? Experimental and clinical issues. PMID- 11773345 TI - Itch, sneeze and wheeze: the genetics of atopic allergy. PMID- 11773346 TI - Can we improve on how we select medical students? PMID- 11773348 TI - Out-of-hours palliative care in the UK: perspectives from general practice and specialist services. AB - Palliative care within the community requires well coordinated multidisciplinary teamworking, involving both primary and secondary care practitioners. 'Out-of hours' periods are a potentially problematic time for delivery of high quality care. We report on two national surveys-one of medical directors of out-of-hours general practitioner cooperatives, the other of medical directors of specialist palliative care units. The aim was to describe general practitioners' and specialists' perspectives on the availability and scope of community nursing and specialist palliative care services. The results point to wide variation in service provision within the community. The two groups differed strikingly in their perceptions, the general practitioners being much less positive than the specialists about the availability of specialist advice and admission to specialist units out of hours. Equitable out-of-hours palliative care services of high quality are unlikely to be achieved without dialogue between primary and secondary care based providers, local needs assessment and adequate resourcing. PMID- 11773347 TI - Injuries among female army recruits: a conflict of legislation. AB - In the final decade of the 20th century, the British Armed Forces came under intense pressure to open up traditionally male roles to female recruits. For training, women were initially given lower entry and exit standards, but it became apparent that many did not possess the strength necessary for their work. This 'gender fair' policy was therefore changed to a 'gender free' policy, whereby identical physical fitness tests were used for selection of male and female recruits and the training programme made no allowances for gender differences. To determine the effects of this policy change, data from medical discharges were examined for the periods before and after implementation, with reference to musculoskeletal injuries of the lower limbs. In the first cohort there were 5697 men and 791 women, in the second 6228 men and 592 women. The cross-gender (F/M) odds ratio for discharges because of overuse injury rose from 4.0 (95% CI 2.8 to 5.7) under the gender-fair system to 7.5 (5.8 to 9.7) under the gender-free system (P=0.001). Despite reducing the number of women selected, the gender-free policy led to higher losses from overuse injuries. This study confirms and quantifies the excess risk for women when they undertake the same arduous training as male recruits, and highlights the conflict between health and safety legislation and equal opportunities legislation. PMID- 11773349 TI - Islet cell transplantation. PMID- 11773350 TI - Ring lesions in the brain and a mass in the kidney. PMID- 11773351 TI - Nitric oxide and prostacyclin in acute interstitial pneumonia. PMID- 11773352 TI - Intravascular lymphoma: a diagnostic enigma. PMID- 11773353 TI - A lump in the penis. PMID- 11773354 TI - Pica with learning disability. PMID- 11773355 TI - Should doctors be the judges of medical orthodoxy? The Barker case of 1920. PMID- 11773356 TI - Revalidation of the retired: bad faith and a worse decision. PMID- 11773357 TI - Treatment of oesophageal cancer. PMID- 11773359 TI - Dysphagia in lung cancer. PMID- 11773360 TI - Leechcraft. PMID- 11773362 TI - Racism in medicine. PMID- 11773363 TI - Counselling and consent in vasectomy. PMID- 11773364 TI - The defence medical services. PMID- 11773365 TI - Impact of chronic illness on the family. PMID- 11773366 TI - Selenium deficiency and HIV-associated cardiomyopathy. PMID- 11773367 TI - Brittle diabetes in the elderly. PMID- 11773368 TI - Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus. AB - Infection by field strains of Foot-and-mouth disease virus (FMDV) is initiated by binding to certain species of arginine-glycine-aspartic acid (RGD)-dependent integrin including alphavbeta3 and the epithelial integrin alphavbeta6. In this report we show that the integrin alphavbeta1, when expressed as a human/hamster heterodimer on transfected CHOB2 cells, is a receptor for FMDV. Virus binding and infection mediated by alphavbeta1 was inefficient in the presence of physiological concentrations of calcium and magnesium but were significantly enhanced by reagents that activate the integrin and promote ligand binding. The ability of chimeric alpha5/alphav integrin subunits, in association with the beta1 chain, to bind FMDV and mediate infection matched the ligand binding specificity of alphavbeta1, not alpha5beta1, thus providing further evidence for the receptor role of alphavbeta1. In addition, data are presented suggesting that amino acid residues near the RGD motif may be important for differentiating between the binding specificities of alphavbeta1 and alphavbeta6. PMID- 11773369 TI - Second-site mutation outside of the U(S)10-12 domain of Deltagamma(1)34.5 herpes simplex virus 1 recombinant blocks the shutoff of protein synthesis induced by activated protein kinase R and partially restores neurovirulence. AB - Earlier studies have shown that herpes simplex virus type 1 (HSV-1) activated protein kinase R (PKR) but that the product of the product of the gamma(1)34.5 gene binds and redirects the host phosphatase 1 to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha). In consequence, the gamma(1)34.5 gene product averts the threatened shutoff of protein synthesis caused by activated PKR. Serial passages of Deltagamma(1)34.5 mutants in human cells led to isolation of two classes of second-site, compensatory mutants. The first, reported earlier, resulted from the juxtaposition of the alpha promoter of the U(S)12 gene to the coding sequence of the U(S)11 gene. The mutant blocks the phosphorylation of eIF-2alpha but does not restore the virulence phenotype of the wild-type virus. We report another class of second-site, compensatory mutants that do not map to the U(S)10-12 domain of the HSV-1 genome. All mutants in this series exhibit sustained late protein synthesis, higher yields in human cells, and reduced phosphorylation of PKR that appears to be phosphatase dependent. Specific dephosphorylation of eIF-2alpha was not demonstrable. At least one mutant in this series exhibited a partial restoration of the virulence phenotype characteristic of the wild-type virus phenotype. The results suggest that the second-site mutations reflect activation of fossilized functions designed to block the interferon response pathways in cells infected with the progenitor of present HSV. PMID- 11773371 TI - Dissociation of genome dimerization from packaging functions and virion maturation of human immunodeficiency virus type 1. AB - The dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome is thought to play important roles at various stages of the virus life cycle. Recently we showed that the DIS/DLS region affects RNA-RNA interaction in intact virus particles, by demonstrating that duplication of the region in viral RNA caused the production of virus particles containing partially monomeric RNAs. We have extended this finding and succeeded for the first time in creating mutant particles which contain only monomeric RNAs without modifying any viral proteins. In terms of RNA encapsidation ability, virion density, and protein processing, the mutant particles were comparable to wild-type particles. The level of production of viral DNA by the mutant virus construct in infected cells was also comparable to that of the constructs that produced exclusively dimeric RNA, indicating that monomeric viral RNA could be the template for strand transfer. These results indicated that the RNA dimerization of HIV-1 could be separated from viral RNA packaging and was not absolutely required for RNA packaging, virion maturation, and reverse transcription. PMID- 11773370 TI - Soluble receptor potentiates receptor-independent infection by murine coronavirus. AB - Mouse hepatitis virus (MHV) infection spreads from MHV-infected DBT cells, which express the MHV receptor CEACAM1 (MHVR), to BHK cells, which are devoid of the receptor, by intercellular membrane fusion (MHVR-independent fusion). This mode of infection is a property of wild-type (wt) JHMV cl-2 virus but is not seen in cultures infected with the mutant virus JHMV srr7. In this study, we show that soluble MHVR (soMHVR) potentiates MHVR-independent fusion in JHMV srr7-infected cultures. Thus, in the presence of soMHVR, JHMV srr7-infected DBT cells overlaid onto BHK cells induce BHK cell syncytia and the spread of JHMV srr7 infection. This does not occur in the absence of soMHVR. soMHVR also enhanced wt virus MHVR independent fusion. These effects were dependent on the concentration of soMHVR in the culture and were specifically blocked by the anti-MHVR monoclonal antibody CC1. Together with these observations, direct binding of soMHVR to the virus spike (S) glycoprotein as revealed by coimmunoprecipitation demonstrated that the effect is mediated by the binding of soMHVR to the S protein. Furthermore, fusion of BHK cells expressing the JHMV srr7 S protein was also induced by soMHVR. These results indicated that the binding of soMHVR to the S protein expressed on the DBT cell surface potentiates the fusion of MHV-infected DBT cells with nonpermissive BHK cells. We conclude that the binding of soMHVR to the S protein converts the S protein to a fusion-active form competent to mediate cell-cell fusion, in a fashion similar to the fusion of virus and cell membranes. PMID- 11773372 TI - Viral dynamics during structured treatment interruptions of chronic human immunodeficiency virus type 1 infection. AB - Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses. PMID- 11773373 TI - Small DNA hairpin negatively regulates in situ priming during duck hepatitis B virus reverse transcription. AB - There are two mutually exclusive pathways for plus-strand DNA synthesis in hepadnavirus reverse transcription. The predominant pathway gives rise to relaxed circular DNA, while the other pathway yields duplex linear DNA. Both pathways use the same RNA primer, which is capped and 18 or 19 nucleotides in length. At the completion of minus-strand DNA synthesis, the final RNase H cleavage generates the plus-strand primer. To make relaxed circular DNA, primer translocation must occur, resulting in the transfer of the primer generated at DR1 to the acceptor site (DR2) near the opposite end of the minus-strand DNA. A small fraction of viruses instead make duplex linear DNA after initiating plus-strand DNA synthesis from DR1, a process called in situ priming. We are interested in understanding the mechanism of discrimination between these two pathways. Some variants of duck hepatitis B virus exhibit high levels of in situ priming due to cis-acting mutations. The mechanism by which these mutations act has been obscure. Sequence inspection predicted formation of a small DNA hairpin in the region overlapping these mutations. We have shown that substitutions disrupting base pairing potential in this hairpin led to increased levels of in situ priming. The introduction of compensatory changes to restore base pairing potential led to reduced levels of in situ priming. Thus, formation of the small DNA hairpin overlapping the 5' end of DR1 in the minus strand contributes to the regulation of primer translocation, at least, through inhibition of in situ priming by making the 3' end of the minus-strand DNA a poor template for initiation. PMID- 11773374 TI - Hepatitis C virus genotype 1b core protein does not exert immunomodulatory effects on virus-induced cellular immunity. AB - The hepatitis C virus (HCV) core protein is among the most conserved proteins in HCV and is known to induce sensitization of cytotoxic T lymphocytes (CTL). Therefore, it is a prime candidate for a component of a potential HCV vaccine. The HCV core protein has, however, been reported to exert multiple effects on cell functions, raising questions as to its suitability for this purpose. This question was investigated here with mice into which replication-deficient adenoviruses expressing core protein of an HCV genotype 1b isolate were injected. We show that induction of cytokines in response to the infection, infiltration of lymphocytes into the infected liver, priming of virus-specific CTL, and liver injury are not modulated by expression of the core protein in the liver. Moreover, no changes in the sensitivity to tumor necrosis factor alpha- or Fas mediated liver injury are demonstrable. A similar lack of demonstrable effects of the core protein on immune functions has also been obtained using transgenic mice expressing another HCV genotype 1b core protein. It is concluded that the HCV core protein of genotype 1b has no modulatory effects on induction of virus specific immune responses and may therefore be a suitable component of an HCV vaccine. PMID- 11773375 TI - Phosphorylation of the Epstein-Barr virus (EBV) DNA polymerase processivity factor EA-D by the EBV-encoded protein kinase and effects of the L-riboside benzimidazole 1263W94. AB - A member of the family of L-riboside benzimidazole compounds, 1263W94, was shown recently to inhibit replication of Epstein-Barr virus (EBV) (V. L. Zacny, E. Gershburg, M. G. Davis, K. K. Biron, and J. S. Pagano, J. Virol. 73:7271-7277, 1999). In the present report the effect of 1263W94 on the phosphorylation pattern of the EBV DNA polymerase processivity factor, EA-D, during viral reactivation in latently EBV-infected Akata cells is analyzed. This pattern specifically changes with progression of cytolytic infection. In the presence of 1263W94 the appearance of the hyperphosphorylated form of EA-D is mainly affected. Next, coexpression of the cloned EBV-encoded protein kinase (EBV PK), BGLF4, with EA-D demonstrated the ability of EBV PK to phosphorylate EA-D to its hyperphosphorylated form in transient assays. However, the phosphorylation of EA D was not directly inhibited by 1263W94 in these coexpression assays. The results indicate that the EBV PK appears to be responsible for the hyperphosphorylation of EA-D, imply that the phosphorylation status of EA-D is important for viral replication, and suggest that 1263W94 acts at a level other than direct inhibition of EA-D phosphorylation by EBV PK. PMID- 11773376 TI - Presence of host ICAM-1 in laboratory and clinical strains of human immunodeficiency virus type 1 increases virus infectivity and CD4(+)-T-cell depletion in human lymphoid tissue, a major site of replication in vivo. AB - Human immunodeficiency virus type 1 (HIV-1) incorporates several host proteins. Earlier studies have indicated that such foreign constituents can modulate the virus life cycle, although the potential roles that these proteins might play in the viral pathology in vivo remain unclear. In an attempt to shed light on this issue, we first exposed explants of human lymphoid tissue to isogenic viruses except for the presence or absence of host-derived ICAM-1. Incorporation of ICAM 1 alone increased HIV-1 infectivity for human tonsillar tissue cultured ex vivo. This observation was made for viruses bearing distinct coreceptor utilization profiles. Conversion of LFA-1 to a high-affinity-high-avidity state for ICAM-1 further augmented the susceptibility of human tonsillar histocultures to infection by ICAM-1-bearing virions. A more massive depletion of CD4(+) T lymphocytes was seen with X4 ICAM-1/POS viruses than with isogenic ICAM-1/NEG virions. Exposure of X4 and R5 primary isolates of HIV-1 to a blocking anti-ICAM 1 antibody resulted in a decrease of virus infection. Finally, X4 and R5 virions derived from a natural human lymphoid tissue microenvironment incorporated high levels of ICAM-1. Altogether, these results indicate that the incorporation of host ICAM-1 can significantly modulate the biology of HIV-1 in a cellular milieu recognized as the major site of replication in vivo and suggest that host proteins found in HIV-1 particles may participate in the pathogenesis of this disease. PMID- 11773377 TI - The late-domain-containing protein p6 is the predominant phosphoprotein of human immunodeficiency virus type 1 particles. AB - The Gag-derived protein p6 of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in the release of virions from the membranes of infected cells. It is presumed that p6 and functionally related proteins from other viruses act as adapters, recruiting cellular factors to the budding site. This interaction is mediated by so-called late domains within the viral proteins. Previous studies had suggested that virus release from the plasma membrane shares elements with the cellular endocytosis machinery. Since protein phosphorylation is known to be a regulatory mechanism in these processes, we have investigated the phosphorylation of HIV-1 structural proteins. Here we show that p6 is the major phosphoprotein of HIV-1 particles. After metabolic labeling of infected cells with [ortho-32P]phosphate, we found that phosphorylated p6 from infected cells and from virus particles consisted of several forms, suggesting differential phosphorylation at multiple sites. Apparently, phosphorylation occurred shortly before or after the release of p6 from Gag and involved only a minor fraction of the total virion-associated p6 molecules. Phosphoamino acid analysis indicated phosphorylation at Ser and Thr, as well as a trace of Tyr phosphorylation, supporting the conclusion that multiple phosphorylation events do occur. In vitro experiments using purified virus revealed that endogenous or exogenously added p6 was efficiently phosphorylated by virion-associated cellular kinase(s). Inhibition experiments suggested that a cyclin-dependent kinase or a related kinase, most likely ERK2, was involved in p6 phosphorylation by virion-associated enzymes. PMID- 11773378 TI - Conserved region CR2 of Epstein-Barr virus nuclear antigen leader protein is a multifunctional domain that mediates self-association as well as nuclear localization and nuclear matrix association. AB - Self-association of viral proteins is important for many of their functions, including enzymatic, transcriptional, and transformational activities. Epstein Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) contains various numbers of W1W2 repeats and a unique carboxyl-terminal Y1Y2 domain. It was reported that EBNA-LP associates with a variety of cellular proteins and plays a critical role in EBV-induced transformation. We report here that EBNA-LP self associates in vivo and the domain responsible for the homotypic association is a multifunctional domain mediating nuclear localization, nuclear matrix association, and EBNA-2-dependent coactivator function of the protein. Our conclusions are based on the following observations. (i) EBNA-LP interacts with itself or its derivatives in the yeast two-hybrid system. (ii) A purified chimeric protein consisting of glutathione S-transferase fused to EBNA-LP specifically formed complexes with EBNA-LP transiently expressed in COS-7 cells. (iii) When Flag epitope-tagged EBNA-LP with either one or two W1W2 repeats and EBNA-LP containing four W1W2 repeats were coexpressed in COS-7 cells, the latter was specifically coimmunoprecipitated with the former. (iv) Mutational analyses of EBNA-LP with deletion mutants revealed that the region between codons 19 and 39 (relative to the first amino acid residue of the W2 domain) is essential for self-association of the protein. The mapped region almost completely overlaps with CR2 and CR3, regions conserved among a subset of primate gamma-herpesviruses and critical for EBNA-2-dependent coactivator function. Amino acid substitutions in CR2 alone abolished the ability of the protein to self-interact. This laboratory previously reported that CR2 is also responsible for nuclear localization and nuclear matrix association (A. Yokoyama, Y. Kawaguchi, I. Kitabayashi, M. Ohki, and K. Hirai, Virology 279:401-413, 2001). (v) Sucrose gradient sedimentation showed that amino acid substitutions in CR2 reduced the ability of the protein to form protein complexes in B cells. These results suggest that self-association of EBNA-LP may be important for its various functions and interactions of the protein with multiple cellular proteins. PMID- 11773379 TI - Adeno-associated virus type 2 Rep78 inhibition of PKA and PRKX: fine mapping and analysis of mechanism. AB - Hormones and neurotransmitters utilize cyclic AMP (cAMP) as a second messenger in signal transduction pathways to regulate cell growth and division, differentiation, gene expression, and metabolism. Adeno-associated virus type 2 (AAV-2) nonstructural protein Rep78 inhibits members of the cAMP signal transduction pathway, the protein kinases PKA and PRKX. We mapped the kinase binding and inhibition domain of Rep78 for PRKX to amino acids (aa) 526 to 561 and that for PKA to aa 526 to 621. These polypeptides were as potent as full length Rep78 in kinase inhibition, which suggests that the kinase-inhibitory domain is entirely contained in these Rep peptides. Steady-state kinetic analysis of Rep78-mediated inhibition of PKA and PRKX showed that Rep78 appears to increase the K(m) value of the peptide kinase substrate, while the maximal velocity of the reaction was unaffected. This indicates that Rep78 acts as a competitive inhibitor with respect to the peptide kinase substrate. We detected homology between a cellular pseudosubstrate inhibitor of PKA, the protein kinase inhibitor PKI, and the PRKX and PKA inhibition domains of Rep78. Due to this homology and the competitive inhibition mechanism of Rep78, we propose that Rep78 inhibits PKA and PRKX kinase activity by pseudosubstrate inhibition. PMID- 11773380 TI - Human cytomegalovirus UL47 tegument protein functions after entry and before immediate-early gene expression. AB - The human cytomegalovirus UL47 open reading frame encodes a 110-kDa protein that is a component of the virion tegument. We have constructed a cytomegalovirus mutant, ADsubUL47, in which the central portion of the UL47 open reading frame has been replaced by two marker genes. The mutant replicated to titers 100-fold lower than those for wild-type virus after infection at either a high or a low input multiplicity in primary human fibroblasts but was substantially complemented on cells expressing UL47 protein. A revertant virus in which the mutation was repaired, ADrevUL47, replicated with wild-type kinetics. Mutant virions lacked UL47 protein and contained reduced amounts of UL48 protein. The mutant was found to be less infectious than wild-type virus, and a defect very early in the replication cycle was observed. Transcription of the viral immediate early 1 gene was delayed by 8 to 10 h. However, this delay was not the result of a defect in virus entry or of the inability of virion proteins to transactivate the major immediate-early promoter. We also show that the UL47 protein coprecipitated with the UL48 and UL69 tegument proteins and the UL86-encoded major capsid protein. We propose that a UL47-containing complex is involved in the release of viral DNA from the disassembling virus particle and that the loss of UL47 protein causes this process to be delayed. PMID- 11773381 TI - Thermostability of reovirus disassembly intermediates (ISVPs) correlates with genetic, biochemical, and thermodynamic properties of major surface protein mu1. AB - Kinetic analyses of infectivity loss during thermal inactivation of reovirus particles revealed substantial differences between virions and infectious subvirion particles (ISVPs), as well as between the ISVPs of reoviruses type 1 Lang (T1L) and type 3 Dearing (T3D). The difference in thermal inactivation of T1L and T3D ISVPs was attributed to the major surface protein mu1 by genetic analyses with reassortant viruses and recoated cores. Irreversible conformational changes in ISVP-bound mu1 were shown to accompany thermal inactivation. The thermal inactivation of ISVPs approximated first-order kinetics over a range of temperatures, permitting the use of Arrhenius plots to estimate activation enthalpies and entropies that account for the different behaviors of T1L and T3D. An effect similar to enthalpy-entropy compensation was additionally noted for the ISVPs of these two isolates. Kinetic analyses with other ISVP-like particles, including ISVPs of a previously reported thermostable mutant, provided further insights into the role of mu1 as a determinant of thermostability. Intact virions, which contain final sigma3 bound to mu1 as their major surface proteins, exhibited greater thermostability than ISVPs and underwent thermal inactivation with kinetics that deviated from first order, suggesting a role for final sigma3 in both these properties. The distinct inactivation behaviors of ISVPs are consistent with their role as an essential intermediate in reovirus entry. PMID- 11773382 TI - Protective effect of avian myelomonocytic growth factor in infection with Marek's disease virus. AB - Marek's disease virus (MDV) is a herpesvirus that induces T lymphomas in chickens. The aim of this study was to assess the role of the macrophage activator chicken myelomonocytic growth factor (cMGF) in controlling MDV infection. B13/B13 chickens, which are highly susceptible to MD, were either treated with cMGF delivered via a live fowlpox virus (fp/cMGF) or treated with the parent vector (fp/M3) or were left as untreated controls. Seven days later, when challenged with the very virulent RB-1B strain of MDV, the spleens of chickens treated with fp/cMGF showed increased expression of the inducible nitric oxide synthase (iNOS) gene compared to those of control chickens and fp/M3 treated chickens. Increased iNOS gene expression was also accompanied by greater induction of gamma interferon and macrophage inflammatory protein (K203) gene expression, both possible activators of iNOS. fp/cMGF treatment also increased the number of monocytes and systemic NO production in contrast to fp/M3 treatment. Even though cMGF treatment was unable to prevent death for the chickens, it did prolong their survival time, and viremia and tumor incidence were greatly reduced. In addition, cMGF treatment improved the partial protection induced by vaccination with HVT (herpesvirus isolated from turkeys) against RB 1B, preventing 100% mortality (versus 66% with vaccination alone) and greatly reducing tumor development. Treatment with fp/M3 did not have such effects. These results suggest that cMGF may play multiple roles in protection against MD. First, it may enhance the innate immune response by increasing the number and activity of monocytes and macrophages, resulting in increased NO production. Second, it may enhance the acquired immune response, indicated by its ability to enhance vaccine efficacy. PMID- 11773383 TI - Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. AB - Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), with influenza pathogenesis in the human respiratory tract and have suggested that alpha and beta interferons are the first cytokines recruited to counteract such infection. However, we report here that TNF-alpha has powerful anti-influenza virus activity. When infected with influenza virus, cultured porcine lung epithelial cells expressed TNF-alpha in a dose-dependent manner. Expression of TNF-alpha was induced only by replicating virus. TNF-alpha showed strong antiviral activity against avian, swine, and human influenza viruses, and the antiviral effect of TNF-alpha was greater than that of gamma or alpha interferon. These findings suggest that TNF-alpha serves as the first line of defense against influenza virus infection in the natural host. PMID- 11773386 TI - Artificial extension of the adenovirus fiber shaft inhibits infectivity in coxsackievirus and adenovirus receptor-positive cell lines. AB - Recent studies demonstrate that virus-cellular receptor interactions are not the sole determinants of adenovirus (Ad) tropism. It has been shown that the fiber shaft length, which ranges from 6 to 23 beta-repeats in human Ads, also influences viral tropism. However, there is no report that investigates whether artificial extension of the shaft alters the infectivity profile of Ad. Therefore, we constructed Ad serotype 5 (Ad5) capsid-based longer-shafted Ad vectors by incorporating Ad2 shaft fragments of different lengths into the Ad5 shaft. We show that "longer-shafted" Ad vectors (up to 32 beta-repeats) could be rescued. We also show that longer-shafted Ad vectors had no impact on knob-CAR (coxsackievirus and Ad receptor) interaction compared to wild-type Ad. Nevertheless, gene transfer efficiencies of longer-shafted Ad vectors were lower in CAR-positive cell lines compared to wild-type Ad. We suggest that artificial extension of the shaft can inhibit infectivity in the context of CAR-positive cell lines without modification of knob-CAR interaction. PMID- 11773384 TI - The cyclin-dependent kinase inhibitor roscovitine inhibits the transactivating activity and alters the posttranslational modification of herpes simplex virus type 1 ICP0. AB - The cyclin-dependent kinase (cdk) inhibitor Roscovitine (Rosco) reduces transcription of herpes simplex virus early genes significantly, even in the presence of wild-type levels of immediate-early (IE) viral proteins, suggesting that the transactivating functions of IE proteins may require the activities of one or more Rosco-sensitive cdk (L. M. Schang, A. Rosenberg, and P. A. Schaffer, J. Virol. 73:2161-2172, 1999). Based on this observation, we sought to determine whether Rosco alters the transactivating activity and posttranslational modification state of the IE protein, infected cell protein 0 (ICP0), in KOS6beta infected Vero cells. KOS6beta is a KOS-derived recombinant virus containing an ICP0-inducible ICP6 promoter::lacZ cassette. To monitor ICP0's transactivating activity, KOS6beta-infected cells were released from a cycloheximide (CHX) mediated protein synthesis block into medium with or without Rosco, and beta galactosidase activity was measured. Rosco inhibited the ability of ICP0 to transactivate the ICP6 promoter by 50-fold. This inhibition was shown not to be a consequence of inhibition of ICP6 basal promoter activity or aberrant nuclear localization of ICP0. Rosco also altered the electrophoretic mobility of a portion of ICP0 molecules derived from KOS-infected cells following reversal of a CHX block. Notably, however, Rosco had only a minimal effect on the phosphorylation state of ICP0. We conclude that ICP0's transactivating activity requires Rosco-sensitive cdks and hypothesize that these cdks regulate the functions of cellular enzymes which modify ICP0, and are, consequently, required for its transactivating activity. Thus, we propose that Rosco regulates ICP0's posttranslational state by mechanisms other than, or in addition to, phosphorylation. PMID- 11773385 TI - Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. AB - Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide. PMID- 11773387 TI - VLA-2 (alpha2beta1) integrin promotes rotavirus entry into cells but is not necessary for rotavirus attachment. AB - In an attempt to identify the rotavirus receptor, we tested 46 cell lines of different species and tissue origins for susceptibility to infection by three N acetyl-neuraminic (sialic) acid (SA)-dependent and five SA-independent rotavirus strains. Susceptibility to SA-dependent or SA-independent rotavirus infection varied depending on the cell line tested and the multiplicity of infection (MOI) used. Cells of renal or intestinal origin and transformed cell lines derived from breast, stomach, bone, or lung were all susceptible to rotavirus infection, indicating a wider host tissue range than previously appreciated. Chinese hamster ovary (CHO), baby hamster kidney (BHK-21), guinea pig colon (GPC-16), rat small intestine (Rie1), and mouse duodenum (MODE-K) cells were found to support only limited rotavirus replication even at MOIs of 100 or 500, but delivery of rotavirus particles into the cytoplasm by lipofection resulted in efficient rotavirus replication. The rotavirus cell attachment protein, the outer capsid spike protein VP4, contains the sequence GDE(A) recognized by the VLA-2 (alpha2beta1) integrin, and to test if VLA-2 is involved in rotavirus attachment and entry, we measured infection in CHO cells that lack VLA-2 and CHO cells transfected with the human alpha2 subunit (CHOalpha2) or with both the human alpha2 and beta1 subunits (CHOalpha2beta1) of VLA-2. Infection by SA-dependent or SA-independent rotavirus strains was 2- to 10-fold more productive in VLA-2 expressing CHO cells than in parental CHO cells, and the increased susceptibility to infection was blocked with anti-VLA-2 antibody. However, the levels of binding of rotavirus to CHO, CHOalpha2, and CHOalpha2beta1 cells were equivalent and were not increased over binding to susceptible monkey kidney (MA104) cells or human colonic adenocarcinoma (Caco-2, HT-29, and T-84) cells, and binding was not blocked by antibody to the human alpha2 subunit. Although the VLA-2 integrin promotes rotavirus infection in CHO cells, it is clear that the VLA-2 integrin alone is not responsible for rotavirus cell attachment and entry. Therefore, VLA 2 is not involved in the initial attachment of rotavirus to cells but may play a role at a postattachment level. PMID- 11773389 TI - A high-capacity, capsid-modified hybrid adenovirus/adeno-associated virus vector for stable transduction of human hematopoietic cells. AB - To achieve stable gene transfer into human hematopoietic cells, we constructed a new vector, DeltaAd5/35.AAV. This vector has a chimeric capsid containing adenovirus type 35 fibers, which conferred efficient infection of human hematopoietic cells. The DeltaAd5/35.AAV vector genome is deleted for all viral genes, allowing for infection without virus-associated toxicity. To generate high capacity DeltaAd5/35.AAV vectors, we employed a new technique based on recombination between two first-generation adenovirus vectors. The resultant vector genome contained an 11.6-kb expression cassette including the human gamma globin gene and the HS2 and HS3 elements of the beta-globin locus control region. The expression cassette was flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs). Infection with DeltaAd5/35.AAV allowed for stable transgene expression in a hematopoietic cell line after integration into the host genome through the AAV ITR(s). This new vector exhibits advantages over existing integrating vectors, including an increased insert capacity and tropism for hematopoietic cells. It has the potential for stable ex vivo transduction of hematopoietic stem cells in order to treat sickle cell disease. PMID- 11773388 TI - Inhibition of interferons by ectromelia virus. AB - Ectromelia virus (EV) is an orthopoxvirus (OPV) that causes mousepox, a severe disease of laboratory mice. Mousepox is a useful model of OPV infection because EV is likely to be a natural mouse pathogen, unlike its close relatives vaccinia virus (VV) and variola virus. Several studies have highlighted the importance of mouse interferons (IFNs) in resistance to and recovery from EV infection, but little is known of the anti-IFN strategies encoded by the virus itself. We have determined that 12 distinct strains and isolates of EV encode soluble, secreted receptors for IFN-gamma (vIFN-gammaR) and IFN-alpha/beta (vIFN-alpha/betaR) that are homologous to those identified in other OPVs. We demonstrate for the first time that the EV vIFN-gammaR has the unique ability to inhibit the biological activity of mouse IFN-gamma. The EV vIFN-alpha/betaR was a potent inhibitor of human and mouse IFN-alpha and human IFN-beta but, surprisingly, was unable to inhibit mouse IFN-beta. The replication of all of the EVs included in our study and of cowpox virus was more resistant than VV to the antiviral effects induced in mouse L-929 cells by IFN-alpha/beta and IFN-gamma. Sequencing studies showed that this EV resistance is likely to be partly mediated by the double-stranded RNA-binding protein encoded by an intact EV homolog of the VV E3L gene. The absence of a functional K3L gene, which encodes a viral eIF-2alpha homolog, in EV suggests that the virus encodes a novel mechanism to counteract the IFN response. These findings will facilitate future studies of the role of viral anti-IFN strategies in mousepox pathogenesis. Their significance in the light of earlier data on the role of IFNs in mousepox is discussed. PMID- 11773390 TI - A six-nucleotide segment within the 3' untranslated region of hibiscus chlorotic ringspot virus plays an essential role in translational enhancement. AB - RNA plant viruses use various translational regulatory mechanisms to control their gene expression. Translational enhancement of viral mRNAs that leads to higher levels of protein synthesis from specific genes may be essential for the virus to successfully compete for cellular translational machinery. The control elements have yet to be analyzed for members of the genus Carmovirus, a small group of plant viruses with positive-sense RNA genomes. In this study, we examined the 3' untranslated region (UTR) of hibiscus chlorotic ringspot virus (HCRSV) genomic RNA (gRNA) and subgenomic RNA (sgRNA) for its role in the translational regulation of viral gene expression. The results showed that the 3' UTR of HCRSV significantly enhanced the translation of several open reading frames on gRNA and sgRNA and a viral gene in a bicistronic construct with an inserted internal ribosome entry site. Through deletion and mutagenesis studies of both the bicistronic construct and full-length gRNA, we demonstrated that a six-nucleotide sequence, GGGCAG, that is complementary to the 3' region of the 18S rRNA and a minimal length of 180 nucleotides are required for the enhancement of translation induced by the 3' UTR. PMID- 11773391 TI - Alterations in NF-kappaB and RBP-Jkappa by arenavirus infection of macrophages in vitro and in vivo. AB - Pichinde virus is an arenavirus that infects guinea pigs and serves as an animal model for human Lassa fever. An attenuated Pichinde virus variant (P2) and a virulent variant (P18) are being used to delineate pathogenic mechanisms that culminate in shock. In guinea pigs, the infection has been shown to begin in peritoneal macrophages following intraperitoneal inoculation and then spreads to the spleen and other reticuloendothelial organs. We show here that infection of the murine monocytic cell line P388D1 with either Pichinde virus variant resulted in the induction of inflammatory cytokines and effectors, including interleukin-6 and tumor necrosis factor alpha. Since these genes are regulated in part by the cellular transcription factors NF-kappaB and RBP-Jkappa, we compared the activities of NF-kappaB and RBP-Jkappa in P388D1 cells following infection with Pichinde virus. The attenuated P2 virus inhibited NF-kappaB activation and caused a shift in the size of the RBP-Jkappa complex. The virulent P18 virus showed less inhibition of NF-kappaB and failed to alter the size of the RBP-Jkappa complex. Peritoneal cells from P2-infected guinea pigs showed induction of NF-kappaB RelA/p50 heterodimer and p50/p50 homodimer and manifested an increase in the size of RBP-Jkappa. By contrast, P18 induced large amounts of the NF-kappaB p50/p50 dimer but failed to induce RelA/p50 or to cause an increase in the RBP-Jkappa size. Taken together, these changes suggest that the attenuated viral strain induces an "activation" of macrophages, while the virulent form of the virus does not. PMID- 11773392 TI - Respiratory syncytial virus fusion protein mediates inhibition of mitogen-induced T-cell proliferation by contact. AB - Human respiratory syncytial virus (HRSV) and bovine respiratory syncytial virus (BRSV) are major pathogens in infants and calves, respectively. Experimental BRSV infection of calves and lambs is associated with lymphopenia and a reduction in responsiveness of peripheral blood lymphocytes (PBLs) to mitogens ex vivo. In this report, we show that in vitro mitogen-induced proliferation of PBLs is inhibited after contact with RSV-infected and UV-inactivated cells or with cells expressing RSV envelope proteins on the cell surface. The protein responsible was identified as the RSV fusion protein (F), as cells infected with a recombinant RSV expressing F as the single envelope protein or cells transfected with a plasmid encoding F were able to induce this effect. Thus, direct contact with RSV F is necessary and sufficient to inhibit proliferation of PBLs. Interestingly, F derived from HRSV was more efficient in inhibiting human PBL proliferation, while F from BRSV was more efficient in inhibiting bovine PBLs. Since various T-cell activation markers were upregulated after presenter cell contact, T lymphocytes are viable and may still be activated by mitogen. However, a significant fraction of PBLs were delayed or defective in G0/G1 to S-phase transit. PMID- 11773393 TI - Replication of subgenomic hepatitis A virus RNAs expressing firefly luciferase is enhanced by mutations associated with adaptation of virus to growth in cultured cells. AB - Replication of hepatitis A virus (HAV) in cultured cells is inefficient and difficult to study due to its protracted and generally noncytopathic cycle. To gain a better understanding of the mechanisms involved, we constructed a subgenomic HAV replicon by replacing most of the P1 capsid-coding sequence from an infectious cDNA copy of the cell culture-adapted HM175/18f virus genome with sequence encoding firefly luciferase. Replication of this RNA in transfected Huh 7 cells (derived from a human hepatocellular carcinoma) led to increased expression of luciferase relative to that in cells transfected with similar RNA transcripts containing a lethal premature termination mutation in 3D(pol) (RNA polymerase). However, replication could not be confirmed in either FrhK4 cells or BSC-1 cells, cells that are typically used for propagation of HAV. Replication was substantially slower than that observed with replicons derived from other picornaviruses, as the basal luciferase activity produced by translation of input RNA did not begin to increase until 24 to 48 h after transfection. Replication of the RNA was reversibly inhibited by guanidine. The inclusion of VP4 sequence downstream of the viral internal ribosomal entry site had no effect on the basal level of luciferase or subsequent increases in luciferase related to its amplification. Thus, in this system this sequence does not contribute to viral translation or replication, as suggested previously. Amplification of the replicon RNA was profoundly enhanced by the inclusion of P2 (but not 5' noncoding sequence or P3) segment mutations associated with adaptation of wild-type virus to growth in cell culture. These results provide a simple reporter system for monitoring the translation and replication of HAV RNA and show that critical mutations that enhance the growth of virus in cultured cells do so by promoting replication of viral RNA in the absence of encapsidation, packaging, and cellular export of the viral genome. PMID- 11773394 TI - Binding of hepatitis C virus-like particles derived from infectious clone H77C to defined human cell lines. AB - Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of viral entry and infection has been hampered by the inability to efficiently propagate the virus in cultured cells and the lack of a small-animal model. Recent studies have shown that in insect cells, the HCV structural proteins assemble into HCV-like particles (HCV-LPs) with morphological, biophysical, and antigenic properties similar to those of putative virions isolated from HCV-infected humans. In this study, we used HCV-LPs derived from infectious clone H77C as a tool to examine virus-cell interactions. The binding of partially purified particles to human cell lines was analyzed by fluorescence activated cell sorting with defined monoclonal antibodies to envelope glycoprotein E2. HCV-LPs demonstrated dose-dependent and saturable binding to defined human lymphoma and hepatoma cell lines but not to mouse cell lines. Binding could be inhibited by monoclonal anti-E2 antibodies, indicating that the HCV-LP-cell interaction was mediated by envelope glycoprotein E2. Binding appeared to be CD81 independent and did not correlate with low-density lipoprotein receptor expression. Heat denaturation of HCV-LPs drastically reduced binding, indicating that the interaction of HCV-LPs with target cells was dependent on the proper conformation of the particles. In conclusion, our data demonstrate that insect cell-derived HCV-LPs bind specifically to defined human cell lines. Since the envelope proteins of HCV-LPs are presumably presented in a virion-like conformation, the binding of HCV-LPs to target cells may allow the study of virus-host cell interactions, including the isolation of HCV receptor candidates and antibody-mediated neutralization of binding. PMID- 11773395 TI - Molecular dissection of the Semliki Forest virus homotrimer reveals two functionally distinct regions of the fusion protein. AB - Semliki Forest virus (SFV) is an enveloped alphavirus that infects cells via a membrane fusion reaction triggered by the acidic pH of endosomes. In response to low pH, the E1 proteins on the virus membrane undergo a series of conformational changes, resulting in the formation of a stable E1 homotrimer. Little is known about the structural basis of either the E1 conformational changes or the resulting homotrimer or about the mechanism of action of the homotrimer in fusion. Here, the E1 homotrimer was formed in vitro from either virus or soluble E1 ectodomain and then probed by various perturbants, proteases, or glycosidase. The preformed homotrimer was extremely stable to moderately harsh conditions and proteases. By contrast, mild reducing conditions selectively disrupted the N terminal region of trimeric E1, making it accessible to proteolytic cleavage and producing E1 fragments that retained trimer interactions. Trypsin digestion produced a fragment missing a portion of the N terminus just proximal to the putative fusion peptide. Digestion with elastase produced several fragments with cleavage sites between residues 78 and 102, resulting in the loss of the putative fusion peptide and the release of membrane-bound E1 ectodomain as a soluble trimer. Elastase also cleaved the homotrimer within an E1 loop located near the fusion peptide in the native E1 structure. Mass spectrometry was used to map the C termini of several differentially produced and fully functional E1 ectodomains. Together, our data identify two separate regions of the SFV E1 ectodomain, one responsible for target membrane association and one necessary for trimer interactions. PMID- 11773396 TI - Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis. AB - The influenza A virus NS1 protein, a virus-encoded alpha/beta interferon (IFN alpha/beta) antagonist, appears to be a key regulator of protein expression in infected cells. We now show that NS1 protein expression results in enhancement of reporter gene activity from transfected plasmids. This effect appears to be mediated at the translational level, and it is reminiscent of the activity of the adenoviral virus-associated I (VAI) RNA, a known inhibitor of the antiviral, IFN induced, PKR protein. To study the effects of the NS1 protein on viral and cellular protein synthesis during influenza A virus infection, we used recombinant influenza viruses lacking the NS1 gene (delNS1) or expressing truncated NS1 proteins. Our results demonstrate that the NS1 protein is required for efficient viral protein synthesis in COS-7 cells. This activity maps to the amino-terminal domain of the NS1 protein, since cells infected with wild-type virus or with a mutant virus expressing a truncated NS1 protein-lacking approximately half of its carboxy-terminal end-showed similar kinetics of viral and cellular protein expression. Interestingly, no major differences in host cell protein synthesis shutoff or in viral protein expression were found among NS1 mutant viruses in Vero cells. Thus, another viral component(s) different from the NS1 protein is responsible for the inhibition of host protein synthesis during viral infection. In contrast to the earlier proposal suggesting that the NS1 protein regulates the levels of spliced M2 mRNA, no effects on M2 protein accumulation were seen in Vero cells infected with delNS1 virus. PMID- 11773397 TI - Mutations of the woodchuck hepatitis virus polymerase gene that confer resistance to lamivudine and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil. AB - Administration of either lamivudine (2'-deoxy-3'-thiacytidine) or L-FMAU (2' fluoro-5-methyl-beta-L-arabinofuranosyluracil) to woodchucks chronically infected with woodchuck hepatitis virus (WHV) induces a transient decline in virus titers. However, within 6 to 12 months, virus titers begin to increase towards pretreatment levels. This is associated with the emergence of virus strains with mutations of the B and C regions of the viral DNA polymerase (T. Zhou et al., Antimicrob. Agents Chemother. 43:1947-1954, 1999; Y. Zhu et al., J. Virol. 75:311 322, 2001). The present study was carried out to determine which of the mutants that we have identified conferred resistance to lamivudine and/or to L-FMAU. When inserted into a laboratory strain of WHV, each of the mutations, or combinations of mutations, of regions B and C produced a DNA replication-competent virus and typically conferred resistance to both nucleoside analogs in cell culture. Sequencing of the polymerase active site also occasionally revealed other mutations, but these did not appear to contribute to drug resistance. Moreover, in transfected cells, most of the mutants synthesized viral DNA nearly as efficiently as wild-type WHV. Computational models suggested that persistence of several of the WHV mutants as prevalent species in the serum and, by inference, liver for up to 6 months following drug withdrawal required a replication efficiency of at least 10 to 30% of that of the wild type. However, their delayed emergence during therapy suggested replication efficiency in the presence of the drug that was still well below that of wild-type WHV in the absence of the drug. PMID- 11773399 TI - Retroviral vectors produced in the cytoplasmic vaccinia virus system transduce intron-containing genes. AB - Introns and polyadenylation (pA) sites are known to improve transcript stability and nuclear-cytoplasmic transport and are normally present in efficient gene expression vectors. Standard retroviral vectors, however, do not allow the inclusion of such sequence elements, as mRNA processing at internal splice and pA sites interferes with the production of functional full-length vector genomes. In this report we examined the capability of hybrid vaccinia/retroviral vectors to transduce complex gene cassettes with nuclear RNA processing signals within the retroviral genome. A retroviral vector was constructed that contains a gene of interest (the human coagulation factor IX [FIX] cDNA), including an intron and an internal pA site. The modified proviral vector genome was cloned downstream of a vaccinia virus promoter and was inserted into the vaccinia virus genome. Infection of a packaging cell line with the recombinant vaccinia virus vector resulted in secretion of retroviral particles at average titers of 10(5) CFU per ml of cell culture supernatant. Due to the cytoplasmic transcription and the nonrecognition of nuclear transcription signals in the vaccinia virus system, full-length transcripts were obtained that still contained the intron. In the retrovirally transduced cell lines the FIX transcripts were terminated at the internal pA site. The transcripts were quantitatively spliced, and FIX was secreted. Recombinant cell lines with stable single-copy inserts containing sequence elements necessary for efficient gene function could be generated. Thus, a relatively simple cytoplasmic system for the generation of complex retroviral vectors is described. Retroviral vectors transducing intron-containing gene cassettes may play a further role in gene therapy applications. PMID- 11773398 TI - A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. AB - After ocular herpes simplex virus type 1 (HSV-1) infection, the virus travels up axons and establishes a lifelong latent infection in neurons of the trigeminal ganglia. LAT (latency-associated transcript), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. The LAT function responsible for this reactivation phenotype is not known. Recently, we showed that LAT can block programmed cell death (apoptosis) in neurons of the trigeminal ganglion in vivo and in tissue culture cells in vitro (G.-C. Perng et al., Science 287:1500-1503, 2000; M. Inman et al., J. Virol. 75:3636-3646, 2001). Consequently, we proposed that this antiapoptosis function may be a key to the mechanism by which LAT enhances reactivation. To study this further, we constructed a recombinant HSV-1 virus in which the HSV-1 LAT gene was replaced by an alternate antiapoptosis gene. We used the bovine herpes virus 1 (BHV-1) latency-related (LR) gene, which was previously shown to have antiapoptosis activity, for this purpose. The resulting chimeric virus, designated CJLAT, contains two complete copies of the BHV-1 LR gene (one in each viral long repeat) in place of the normal two copies of the HSV-1 LAT, on an otherwise wild-type HSV-1 strain McKrae genomic background. We report here that in both rabbits and mice reactivation of CJLAT was significantly greater than the LAT null mutant dLAT2903 (P < 0.0004 and P = 0.001, respectively) and was at least as efficient as wild-type McKrae. This strongly suggests that a BHV-1 LR gene function was able to efficiently substitute for an HSV-1 LAT gene function involved in reactivation. Although replication of CJLAT in rabbits and mice was similar to that of wild-type McKrae, CJLAT killed more mice during acute infection and caused more corneal scarring in latently infected rabbits. This suggested that the BHV-1 LR gene and the HSV-1 LAT gene are not functionally identical. However, LR and LAT both have antiapoptosis activity. These studies therefore strongly support the hypothesis that replacing LAT with an antiapoptosis gene restores the wild-type reactivation phenotype to a LAT null mutant of HSV-1 McKrae. PMID- 11773400 TI - Molecular phylogeny and proposed classification of the simian picornaviruses. AB - The simian picornaviruses were isolated from various primate tissues during the development of general tissue culture methods in the 1950s to 1970s or from specimens derived from primates used in biomedical research. Twenty simian picornavirus serotypes are recognized, and all are presently classified within the Enterovirus genus. To determine the phylogenetic relationships among all of the simian picornaviruses and to evaluate their classification, we have determined complete VP1 sequences for 19 of the 20 serotypes. Phylogenetic analysis showed that A13, SV19, SV26, SV35, SV43, and SV46 are members of human enterovirus species A, a group that contains enterovirus 71 and 11 of the coxsackie A viruses. SA5 is a member of human enterovirus species B, which contains the echoviruses, coxsackie B viruses, coxsackievirus A9, and enterovirus 69. SV6, N125, and N203 are related to one another and, more distantly, to species A human enteroviruses, but could not be definitely assigned to a species. SV4 and SV28 are closely related to one another and to A-2 plaque virus, but distinct from other enteroviruses, suggesting that these simian viruses are members of a new enterovirus species. SV2, SV16, SV18, SV42, SV44, SV45, and SV49 are related to one another but distinct from viruses in all other picornavirus genera, suggesting that they may comprise a previously unknown genus in Picornaviridae. Several simian virus VP1 sequences (N125 and N203; SV4 and SV28; SV19, SV26, and SV35; SV18 and SV44; SV16, SV42, and SV45) are greater than 75% identical to one another (and/or greater than 85% amino acid identity), suggesting that the true number of distinct serotypes among the viruses surveyed is less than 20. PMID- 11773401 TI - Proteolytic processing of human cytomegalovirus glycoprotein B is dispensable for viral growth in culture. AB - Glycoprotein B (gB) of human cytomegalovirus (HCMV), which is considered essential for the viral life cycle, is proteolytically processed during maturation. Since gB homologues of several other herpesviruses remain uncleaved, the relevance of this property of HCMV gB for viral infectivity is unclear. Here we report on the construction of a viral mutant in which the recognition site of gB for the cellular endoprotease furin was destroyed. Because mutagenesis of essential proteins may result in a lethal phenotype, a replication-deficient HCMV gB-null genome encoding enhanced green fluorescent protein was constructed, and complementation by mutant gBs was initially evaluated in transient-cotransfection assays. Cotransfection of plasmids expressing authentic gB or gB with a mutated cleavage site (gB-DeltaFur) led to the formation of green fluorescent miniplaques which were considered to result from one cycle of phenotypic complementation of the gB-null genome. To verify these results, two recombinant HCMV genomes were constructed: HCMV-BAC-DeltaMhdI, with a deletion of hydrophobic domain 1 of gB that appeared to be essential for viral growth in the cotransfection experiments, and HCMV-BACDeltaFur, in which the gB cleavage site was mutated by amino acid substitution. Consistent with the results of the cotransfection assays, only the DeltaFur mutant replicated in human fibroblasts, showing growth kinetics comparable to that of wild-type virus. gB in mutant-infected cells was uncleaved, whereas glycosylation and transport to the cell surface were not impaired. Extracellular mutant virus contained exclusively uncleaved gB, indicating that proteolytic processing of gB is dispensable for viral replication in cell culture. PMID- 11773402 TI - Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR. AB - The hepatitis C virus (HCV) envelope protein E2 has been shown to accumulate in the lumen of the endoplasmic reticulum (ER) as a properly folded glycoprotein as well as large aggregates of misfolded proteins. In the present study, we have identified an additional unglycosylated species, with an apparent molecular mass of 38 kDa (E2-p38). In contrast to the glycosylated E2, E2-p38 is significantly less stable and is degraded through the proteasome pathway. Correspondingly, E2 p38 is found to be ubiquitinated. E2-p38 is localized mostly in the cytosol, in contrast to the glycosylated form, which is exclusively membrane associated. Alpha interferon (IFN-alpha) treatment or overexpression of the double-stranded RNA-activated protein kinase (PKR) significantly increased the stability of E2 p38, consistent with a previous report (D. R. Taylor, S. T. Shi, P. R. Romano, G. N. Barber, and M. M. Lai, Science 285:107-110, 1999) that E2 interacts with PKR and inhibits its kinase activity. Direct interaction between PKR and E2-p38, but not the glycosylated form of E2, was also observed. These results show that E2 p38 is the form of E2 that interacts with PKR in the cytosol and may contribute to the resistance of HCV to IFN-alpha. Thus, an ER protein can exist in the cytosol as an unglycosylated species and impair cellular functions. PMID- 11773403 TI - The cytoplasmic tail of infectious bronchitis virus E protein directs Golgi targeting. AB - We have previously shown that the E protein of the coronavirus infectious bronchitis virus (IBV) is localized to the Golgi complex when expressed exogenously from cDNA. Here, we report that neither the transmembrane domain nor the short lumenal domain of IBV E is required for Golgi targeting. However, an N terminal truncation containing only the cytoplasmic domain (CTE) was efficiently localized to the Golgi complex, and this domain could retain a reporter protein in the Golgi. Thus, the cytoplasmic tail of the E protein is necessary and sufficient for Golgi targeting. The IBV E protein is palmitoylated on one or two cysteine residues adjacent to its transmembrane domain, but palmitoylation was not required for proper Golgi targeting. Using C-terminal truncations, we determined that the IBV E Golgi targeting information is present between tail amino acids 13 and 63. Upon treatment with brefeldin A, both the E and CTE proteins redistributed to punctate structures that colocalized with the Golgi matrix proteins GM130 and p115 instead of being localized to the endoplasmic reticulum like Golgi glycosylation enzymes. This suggests that IBV E is associated with the Golgi matrix through interactions of its cytoplasmic tail and may have interesting implications for coronavirus assembly in early Golgi compartments. PMID- 11773404 TI - Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. AB - Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection. PMID- 11773405 TI - Transcription regulatory sequences and mRNA expression levels in the coronavirus transmissible gastroenteritis virus. AB - The transcription regulatory sequences (TRSs) of the coronavirus transmissible gastroenteritis virus (TGEV) have been characterized by using a helper virus dependent expression system based on coronavirus-derived minigenomes to study the synthesis of subgenomic mRNAs. The TRSs are located at the 5' end of TGEV genes and include a highly conserved core sequence (CS), 5'-CUAAAC-3', that is essential for mediating a 100- to 1,000-fold increase in mRNA synthesis when it is located in the appropriate context. The relevant sequences contributing to TRS activity have been studied by extending the CS 5' upstream and 3' downstream. Sequences from virus genes flanking the CS influenced transcription levels from moderate (10- to 20-fold variation) to complete mRNA synthesis silencing, as shown for a canonical CS at nucleotide (nt) 120 from the initiation codon of the S gene that did not lead to the production of the corresponding mRNA. An optimized TRS has been designed comprising 88 nt from the N gene TRS, the CS, and 3 nt 3' to the M gene CS. Further extension of the 5'-flanking nucleotides (i.e., by 176 nt) decreased subgenomic RNA levels. The expression of a reporter gene (beta-glucuronidase) by using the selected TRS led to the production of 2 to 8 microg of protein per 10(6) cells. The presence of an appropriate Kozak context led to a higher level of protein expression. Virus protein levels were shown to be dependent on transcription and translation regulation. PMID- 11773406 TI - Relative neurotropism of a recombinant rhabdovirus expressing a green fluorescent envelope glycoprotein. AB - A new recombinant vesicular stomatitis virus (rVSV) that expresses green fluorescent protein (GFP) on the cytoplasmic domain of the VSV glycoprotein (G protein) was used in the mouse as a model for studying brain infections by a member of the Mononegavirales order that can cause permanent changes in behavior. After nasal administration, virus moved down the olfactory nerve, first to periglomerular cells, then past the mitral cell layer to granule cells, and finally to the subventricular zone. Eight days postinoculation, rVSV was eliminated from the olfactory bulb. Little sign of infection could be found outside the olfactory system, suggesting that anterograde or retrograde axonal transport of rVSV was an unlikely mechanism for movement of rVSV out of the bulb. When administered intracerebrally by microinjection, rVSV spread rapidly within the brain, with strong infection at the site of injection and at some specific periventricular regions of the brain, including the dorsal raphe, locus coeruleus, and midline thalamus; the ventricular system may play a key role in rapid rVSV dispersion within the brain. Thus, the lack of VSV movement out of the olfactory system was not due to the absence of potential for infections in other brain regions. In cultures of both mouse and human central nervous system (CNS) cells, rVSV inoculations resulted in productive infection, expression of the G GFP fusion protein in the dendritic and somatic plasma membrane, and death of all neurons and glia, as detected by ethidium homodimer nuclear staining. Although considered a neurotropic virus, rVSV also infected heart, skin, and kidney cells in dispersed cultures. rVSV showed a preference for immature neurons in vitro, as shown by enhanced viral infection in developing hippocampal cultures and in the outer granule cell layer in slices of developing cerebellum. Together, these data suggest a relative affinity of rVSV for some neuronal types in the CNS, adding to our understanding of the long-lasting changes in rodent behavior found after transient VSV infection. PMID- 11773407 TI - The rat cytomegalovirus R33-encoded G protein-coupled receptor signals in a constitutive fashion. AB - The rat cytomegalovirus (RCMV) R33 gene is conserved among all betaherpesviruses and encodes a protein (pR33) that shows sequence similarity with chemokine binding G protein-coupled receptors (GPCRs). Previously, the physiological significance of the R33 gene was demonstrated by the finding that an RCMV strain with R33 deleted is severely attenuated in vivo and is unable to either enter or replicate in the salivary glands of infected rats. Here, we report that RCMV pR33 is expressed as a functional GPCR that signals in an agonist-independent manner in both COS-7 and Rat2 cells. Transient expression of pR33 in COS-7 cells results in constitutive activation of phospholipase C (PLC) due to coupling to G proteins of the G(q) class. Interestingly, PLC activation is partially inhibited by cotransfection with G(alpha)-transducin subunits, which indicates the involvement of G(betagamma) as well as Galpha subunits in pR33-mediated signaling. Surprisingly, PLC activation is also partially inhibited by addition of pertussis toxin (PTX), suggesting that pR33 activates not only G(q) but also G(i/0) proteins. The constitutive activation of G(i/0) proteins by pR33 is further demonstrated by the PTX-sensitive decrease of CRE-mediated transcription and the PTX-sensitive increase of both NF-kappaB- and SRE-mediated transcription. In contrast to its homolog of human herpesvirus 6B (pU12), pR33 does not bind RANTES. PMID- 11773408 TI - Analyses of genotypic diversity among North, South, and Central American isolates of sugarcane yellow leaf virus: evidence for Colombian origins and for intraspecific spatial phylogenetic variation. AB - We have analyzed the genotypic diversity of sugarcane yellow leaf virus (SCYLV) collected from North, South, and Central America by fingerprinting assays and selective cDNA cloning and sequencing. One group of isolates from Colombia, designated the C-population, has been identified as residing at the root node between a separable superpopulation structure of SCYLV and other members of the family Luteoviridae, indicating that the progenitor viruses of the North, South, and Central American isolates of the SCYLV superpopulation most likely arose from a C-population structure. From a model of intrafamilial evolution (F. Moonan et al., Virology 269:156-171, 2000), a prediction could be made that within the SCYLV species, the capacity of genomic sequence divergence would range from lowest in the capsid protein open reading frame 3 (ORF 3) to highest in a region spanning across the carboxy-terminal end of the RNA-dependent RNA polymerase ORF. We have demonstrated the validity and applicability of this intrafamilial model for the prediction of intraspecies SCYLV diversity. Analysis of spatial phylogenetic variation (SPV) within the SCYLV isolates could not be assessed by application of a "partial likelihoods assessed through optimization" (PLATO) derived intraspecies model alone. However, application of a PLATO-derived intrafamilial model with the intraspecies-derived model allowed distinction of three forms of SPV. Two of the SPV forms identified correspond to the extremes in a continuum of sequence evolution displayed in a SCYLV superpopulation structure, and the third form was diagnostic of a C-population structure. The application of these types of models has value in terms of predicting the types of SCYLV intraspecies diversity that may exist worldwide, and in general, may be useful in application for more informed design of transgenes for use in the elicitation of homology-dependent virus resistance mechanisms in transgenic plants. PMID- 11773409 TI - A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC 126), and selection of a novel (A28S) mutation in the protease active site. AB - We identified UIC-94003, a nonpeptidic human immunodeficiency virus (HIV) protease inhibitor (PI), containing 3(R),3a(S),6a(R)-bis-tetrahydrofuranyl urethane (bis-THF) and a sulfonamide isostere, which is extremely potent against a wide spectrum of HIV (50% inhibitory concentration, 0.0003 to 0.0005 microM). UIC-94003 was also potent against multi-PI-resistant HIV-1 strains isolated from patients who had no response to any existing antiviral regimens after having received a variety of antiviral agents (50% inhibitory concentration, 0.0005 to 0.0055 microM). Upon selection of HIV-1 in the presence of UIC-94003, mutants carrying a novel active-site mutation, A28S, in the presence of L10F, M46I, I50V, A71V, and N88D appeared. Modeling analysis revealed that the close contact of UIC 94003 with the main chains of the protease active-site amino acids (Asp29 and Asp30) differed from that of other PIs and may be important for its potency and wide-spectrum activity against a variety of drug-resistant HIV-1 variants. Thus, introduction of inhibitor interactions with the main chains of key amino acids and seeking a unique inhibitor-enzyme contact profile should provide a framework for developing novel PIs for treating patients harboring multi-PI-resistant HIV 1. PMID- 11773410 TI - Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease. AB - Resistance to human immunodeficiency virus type 1 protease (HIV PR) inhibitors results primarily from the selection of multiple mutations in the protease region. Because many of these mutations are selected for the ability to decrease inhibitor binding in the active site, they also affect substrate binding and potentially substrate specificity. This work investigates the substrate specificity of a panel of clinically derived protease inhibitor-resistant HIV PR variants. To compare protease specificity, we have used positional-scanning, synthetic combinatorial peptide libraries as well as a select number of individual substrates. The subsite preferences of wild-type HIV PR determined by using the substrate libraries are consistent with prior reports, validating the use of these libraries to compare specificity among a panel of HIV PR variants. Five out of seven protease variants demonstrated subtle differences in specificity that may have significant impacts on their abilities to function in viral maturation. Of these, four variants demonstrated up to fourfold changes in the preference for valine relative to alanine at position P2 when tested on individual peptide substrates. This change correlated with a common mutation in the viral NC/p1 cleavage site. These mutations may represent a mechanism by which severely compromised, drug-resistant viral strains can increase fitness levels. Understanding the altered substrate specificity of drug-resistant HIV PR should be valuable in the design of future generations of protease inhibitors as well as in elucidating the molecular basis of regulation of proteolysis in HIV. PMID- 11773411 TI - Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype. AB - We have previously observed that selected influenza virus hemagglutinin (HA) specific monoclonal antibodies (MAbs) with poor virus-neutralizing (VN) activity in vitro exhibited greatly enhanced VN activity in vivo after administration to SCID mice. The same Abs displayed improved VN activity also when tested in vitro in the presence of noninactivated serum from SCID mice. To identify Ab-dependent properties and serum components that contributed to enhancement of Ab activity, we screened a large panel of HA-specific MAbs for hemagglutination inhibition (HI) in the presence of noninactivated serum from naive mice (NMS). We found that HI activity was enhanced by NMS depending on the Ab's fine specificity (antigenic region Cb/E > Ca/A,D > Sa,Sb/B), its heavy-chain isotype (immunoglobulin G2 [IgG2] > IgG3; IgG1 and IgM negative), and to some extent also on its derivation (primary response > memory response). On average, the HI activity of Cb/E specific MAbs of the IgG2 isotype isolated from the primary response was enhanced by 20-fold. VN activity was enhanced significantly but less strongly than HI activity. Enhancement (i) was destroyed by heat inactivation (30 min, 56 degrees C); (ii) did not require C3, the central complement component; (iii) was abolished by treatment of serum with anti-C1q; and (iv) could be reproduced with purified C1q, the binding moiety of C1, the first complement component. We believe that this is the first description of a direct C1q-mediated enhancement of antiviral Ab activities. PMID- 11773412 TI - Molecular chaperone Hsp90 is important for vaccinia virus growth in cells. AB - Molecular chaperones assist protein folding, and some chaperones are induced by heat, nutrient depletion, or pathogen invasion. This study investigates the role played by Hsp90 in the life cycle of vaccinia virus. The titer of vaccinia intracellular mature virions (IMV) was reduced by 2 orders of magnitude in RK13 cells treated with geldanamycin (GA), which blocks the ATPase activity of Hsp90. GA does not affect expression from the viral early promoter, but treatment with GA delays DNA replication and intermediate gene transcription and reduces expression from the viral late promoter. Vaccinia virus infection does not induce Hsp90 expression; however, intracellular distribution of Hsp90 is altered in virus-infected cells. Hsp90 is restricted to the cytoplasm of mock-infected cells; in contrast, Hsp90 is transiently associated with virosomes in virus infected cells although it is not incorporated into IMV. In addition, Hsp90 interacts with viral core protein 4a, the mature form of the A10L gene product, in virus-infected cells. In conclusion, these results suggest that a cellular chaperone protein, Hsp90, is important for vaccinia virus growth in cultured cells and that viral core protein 4a associates with Hsp90-containing complexes in the infected cells. PMID- 11773413 TI - Influenza a virus M2 ion channel activity is essential for efficient replication in tissue culture. AB - The amantadine-sensitive ion channel activity of influenza A virus M2 protein was discovered through understanding the two steps in the virus life cycle that are inhibited by the antiviral drug amantadine: virus uncoating in endosomes and M2 protein-mediated equilibration of the intralumenal pH of the trans Golgi network. Recently it was reported that influenza virus can undergo multiple cycles of replication without M2 ion channel activity (T. Watanabe, S. Watanabe, H. Ito, H. Kida, and Y. Kawaoka, J. Virol. 75:5656-5662, 2001). An M2 protein containing a deletion in the transmembrane (TM) domain (M2-del(29-31)) has no detectable ion channel activity, yet a mutant virus was obtained containing this deletion. Watanabe and colleagues reported that the M2-del(29-31) virus replicated as efficiently as wild-type (wt) virus. We have investigated the effect of amantadine on the growth of four influenza viruses: A/WSN/33; N31S-M2WSN, a mutant in which an asparagine residue at position 31 in the M2 TM domain was replaced with a serine residue; MUd/WSN, which possesses seven RNA segments from WSN plus the RNA segment 7 derived from A/Udorn/72; and A/Udorn/72. N31S-M2WSN was amantadine sensitive, whereas A/WSN/33 was amantadine resistant, indicating that the M2 residue N31 is the sole determinant of resistance of A/WSN/33 to amantadine. The growth of influenza viruses inhibited by amantadine was compared to the growth of an M2-del(29-31) virus. We found that the M2-del(29-31) virus was debilitated in growth to an extent similar to that of influenza virus grown in the presence of amantadine. Furthermore, in a test of biological fitness, it was found that wt virus almost completely outgrew M2-del(29-31) virus in 4 days after cocultivation of a 100:1 ratio of M2-del(29-31) virus to wt virus, respectively. We conclude that the M2 ion channel protein, which is conserved in all known strains of influenza virus, evolved its function because it contributes to the efficient replication of the virus in a single cycle. PMID- 11773414 TI - Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase. AB - G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic alpha-helix rich in arginine residues. Subtle mutation of this alpha-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13(II) and G4 accessory proteins opens new prospects for treatment of retrovirus induced leukemia. PMID- 11773415 TI - The g5R (D250) gene of African swine fever virus encodes a Nudix hydrolase that preferentially degrades diphosphoinositol polyphosphates. AB - The African swine fever virus (ASFV) g5R gene encodes a protein containing a Nudix hydrolase motif which in terms of sequence appears most closely related to the mammalian diadenosine tetraphosphate (Ap4A) hydrolases. However, purified recombinant g5R protein (g5Rp) showed a much wider range of nucleotide substrate specificity compared to eukaryotic Ap4A hydrolases, having highest activity with GTP, followed by adenosine 5'-pentaphosphate (p5A) and dGTP. Diadenosine and diguanosine nucleotides were substrates, but the enzyme showed no activity with cap analogues such as 7mGp3A. In common with eukaryotic diadenosine hexaphosphate (Ap6A) hydrolases, which prefer higher-order polyphosphates as substrates, g5Rp also hydrolyzes the diphosphoinositol polyphosphates PP-InsP5 and [PP]2-InsP4. A comparison of the kinetics of substrate utilization showed that the k(cat)/K(m) ratio for PP-InsP5 is 60-fold higher than that for GTP, which allows classification of g5R as a novel diphosphoinositol polyphosphate phosphohydrolase (DIPP). Unlike mammalian DIPP, g5Rp appeared to preferentially remove the 5-beta phosphate from both PP-InsP5 and [PP]2-InsP4. ASFV infection led to a reduction in the levels of PP-InsP5, ATP and GTP by ca. 50% at late times postinfection. The measured intracellular concentrations of these compounds were comparable to the respective K(m) values of g5Rp, suggesting that one or all of these may be substrates for g5Rp during ASFV infection. Transfection of ASFV-infected Vero cells with a plasmid encoding epitope-tagged g5Rp suggested localization of this protein in the rough endoplasmic reticulum. These results suggest a possible role for g5Rp in regulating a stage of viral morphogenesis involving diphosphoinositol polyphosphate-mediated membrane trafficking. PMID- 11773416 TI - Heterologous gene expression from transmissible gastroenteritis virus replicon particles. AB - We have recently isolated a transmissible gastroenteritis virus (TGEV) infectious construct designated TGEV 1000 (B. Yount, K. M. Curtis, and R. S. Baric, J. Virol. 74:10600-10611, 2000). Using this construct, a recombinant TGEV was constructed that replaced open reading frame (ORF) 3A with a heterologous gene encoding green fluorescent protein (GFP). Following transfection of baby hamster kidney (BHK) cells, a recombinant TGEV (TGEV-GFP2) was isolated that replicated efficiently and expressed GFP. Replicon constructs were constructed that lacked either the ORF 3B and E genes or the ORF 3B, E, and M genes [TGEV-Rep(AvrII) and TGEV-Rep(EcoNI), respectively]. As the E and M proteins are essential for TGEV virion budding, these replicon RNAs should replicate but not result in the production of infectious virus. Following cotransfection of BHK cells with the replicon RNAs carrying gfp, GFP expression was evident by fluorescent microscopy and leader-containing transcripts carrying gfp were detected by reverse transcription-PCR (RT-PCR). Subsequent passage of cell culture supernatants onto permissive swine testicular (ST) cells did not result in the virus, GFP expression, or the presence of leader-containing subgenomic transcripts, demonstrating the single-hit nature of the TGEV replicon RNAs. To prepare a packaging system to assemble TGEV replicon particles (TGEV VRP), the TGEV E gene was cloned into a Venezuelan equine encephalitis (VEE) replicon expression vector and VEE replicon particles encoding the TGEV E protein were isolated [VEE TGEV(E)]. BHK cells were either cotransfected with TGEV-Rep(AvrII) (E gene deletion) and VEE-TGEV(E) RNA transcripts or transfected with TGEV-Rep(AvrII) RNA transcripts and subsequently infected with VEE VRPs carrying the TGEV E gene. In both cases, GFP expression and leader-containing GFP transcripts were detected in transfected cells. Cell culture supernatants, collected approximately 36 h posttransfection, were passed onto fresh ST cells where GFP expression was evident approximately 18 h postinfection. Leader-containing GFP transcripts containing the ORF 3B and E gene deletions were detected by RT-PCR. Recombinant TGEV was not released from these cultures. Under identical conditions, TGEV-GFP2 spread throughout ST cell cultures, expressed GFP, and formed viral plaques. The development of infectious TGEV replicon particles should assist studies of TGEV replication and assembly as well as facilitate the production of novel swine candidate vaccines. PMID- 11773418 TI - Identification of glycoprotein gpTRL10 as a structural component of human cytomegalovirus. AB - Human cytomegalovirus (HCMV) has a coding capacity for glycoproteins which far exceeds that of other herpesviruses. Few of these proteins have been characterized. We have investigated the gene product(s) of reading frame 10, which is present in both the internal and terminal repeat regions of HCMV strain AD169 and only once in clinical isolates. The putative protein product is a 171 amino-acid glycoprotein with a theoretical mass of 20.5 kDa. We characterized the protein encoded by this reading frame in the laboratory strain AD169 and a recent isolate, TB40E. The results from both strains were comparable. Northern blot analyses showed that the gene was transcribed with early/late kinetics. Two proteins of 22 and 23.5-kDa were detected in virus-infected cells and in cells transiently expressing recombinant TRL10. Both forms contained only high-mannose linked carbohydrate modifications. In addition, virus-infected cells expressed small amounts of the protein modified with complex N-linked sugars. Image analysis localized transiently expressed TRL10 to the endoplasmic reticulum. Immunoblot analyses as well as immunoelectron microscopy of purified virions demonstrated that TRL10 represents a structural component of the virus particle. Immunoblot analysis in the absence of reducing agents indicated that TRL10, like the other HCMV envelope glycoproteins, is present in a disulfide-linked complex. Sequence analysis of the TRL10 coding region in nine low-passage clinical isolates revealed strain-specific variation. In summary, the protein product of the TRL10 open reading frame represents a novel structural glycoprotein of HCMV and was termed gpTRL10. PMID- 11773417 TI - The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway. AB - Herpes simplex virus type 1 (HSV-1) and HSV-2 trigger or counteract apoptosis by a cell-specific mechanism. Our studies are based on previous findings that the protein kinase (PK) domain of the large subunit of HSV-2 ribonucleotide reductase (ICP10) activates the Ras/MEK/MAPK pathway (Smith et al., J. Virol. 74:10417, 2000). Because survival pathways can modulate apoptosis, we used cells that are stably or transiently transfected with ICP10 PK, an HSV-2 mutant deleted in ICP10 PK (ICP10DeltaPK) and the MEK-specific inhibitor U0126 to examine the role of ICP10 PK in apoptosis. Apoptosis was induced by staurosporine or D-mannitol in human (HEK293) cells or HEK293 cells stably transfected with the ICP10 PK negative mutant p139 (JHL15), as determined by morphology, DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage. HEK293 cells stably transfected with ICP10 (JHLa1) were protected from apoptosis. ICP10 but not p139 protected neuronally differentiated PC12 cells from death due to nerve growth factor withdrawal, and apoptosis (determined by TUNEL) and caspase-3 activation were seen in primary hippocampal cultures infected with ICP10DeltaPK but not with HSV-2 or a revertant virus [HSV-2(R)]. The data indicate that ICP10 has antiapoptotic activity under both paradigms and that it requires a functional PK activity. The apoptotic cells in primary hippocampal cultures were neurons, as determined by double immunofluorescence with fluorescein-labeled dUTP (TUNEL) and phycoerythrin-labeled antibodies specific for neuronal proteins (TuJ1 and NF-160). Protection from apoptosis was associated with MEK/MAPK activation, as evidenced by (i) increased levels of activated (phosphorylated) MAPK in HSV-2- but not ICP10DeltaPK-infected cultures and (ii) inhibition of MAPK activation by the MEK-specific inhibitor U0126. MEK and MAPK were activated by infection with UV-inactivated but not antibody-neutralized HSV 2, suggesting that activation requires cellular penetration but is independent of de novo viral protein synthesis. PMID- 11773419 TI - Adenovirus E1A N-terminal amino acid sequence requirements for repression of transcription in vitro and in vivo correlate with those required for E1A interference with TBP-TATA complex formation. AB - The adenovirus (Ad) E1A 243R oncoprotein encodes an N-terminal transcription repression domain that is essential for early viral functions, cell immortalization, and cell transformation. The transcription repression function requires sequences within amino acids 1 to 30 and 48 to 60. To elucidate the roles of the TATA-binding protein (TBP), p300, and the CREB-binding protein (CBP) in the mechanism(s) of E1A repression, we have constructed 29 amino acid substitution mutants and 5 deletion mutants spanning the first 30 amino acids within the E1A 1-80 polypeptide backbone. These mutant E1A polypeptides were characterized with regard to six parameters: the ability to repress transcription in vitro and in vivo, to disrupt TBP-TATA box interaction, and to bind TBP, p300, and CBP. Two regions within E1A residues 1 to 30, amino acids 2 to 6 and amino acid 20, are critical for E1A transcription repression in vitro and in vivo and for the ability to interfere with TBP-TATA interaction. Replacement of 6Cys with Ala in the first region yields the most defective mutant. Replacement of 20Leu with Ala, but not substitutions in flanking residues, yields a substantially defective phenotype. Protein binding assays demonstrate that replacement of 6Cys with Ala yields a mutant completely defective in interaction with TBP, p300, and CBP. Our findings are consistent with a model in which the E1A repression function involves interaction of E1A with p300/CBP and interference with the formation of a TBP-TATA box complex. PMID- 11773420 TI - E4orf6 variants with separate abilities to augment adenovirus replication and direct nuclear localization of the E1B 55-kilodalton protein. AB - The E4orf6 protein of group C adenovirus is an oncoprotein that, in association with the E1B 55-kDa protein and by E1B-independent means, promotes virus replication. An arginine-faced amphipathic alpha-helix in the E4orf6 protein is required for the E4orf6 protein to direct nuclear localization of the E1B 55-kDa protein and to enhance replication of an E4 deletion virus. In this study, E4orf6 protein variants containing arginine substitutions in the amphipathic alpha-helix were analyzed. Two of the six arginine residues within the alpha-helix, arginine 241 and arginine-243, were critical for directing nuclear localization of the E1B 55-kDa protein. The four remaining arginine residues appear to provide a net positive charge for the E4orf6 protein to direct nuclear localization of the E1B 55-kDa protein. The molecular determinants of the arginine-faced amphipathic alpha-helix that were required for the functional interaction between the E4orf6 and E1B 55-kDa proteins seen in the transfected cell differed from those required to support a productive infection. Several E4orf6 protein variants with arginine to-glutamic acid substitutions that failed to direct nuclear localization of the E1B 55-kDa protein restored replication of an E4 deletion virus. Additionally, a variant containing an arginine-to-alanine substitution at position 243 that directed nuclear localization of the E1B 55-kDa protein failed to enhance virus replication. These results indicate that the ability of the E4orf6 protein to relocalize the E1B 55-kDa protein to the nucleus can be separated from the ability of the E4orf6 protein to support a productive infection. PMID- 11773421 TI - Oncoretrovirus and lentivirus vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: generation, concentration, and broad host range. AB - Lymphocytic choriomeningitis virus (LCMV) is a noncytopathic arenavirus shown to infect a broad range of different cell types. Here, we combined the beneficial characteristics of the LCMV glycoprotein (LCMV-GP) and those of retroviral vectors to generate a new, safe, and efficient gene transfer system. These LCMV GP pseudotypes were systematically compared with vectors containing the widely used amphotropic murine leukemia virus envelope (A-MLVenv) or the vesicular stomatitis virus G protein (VSV-G). Production of LCMV-GP-pseudotyped oncoretroviral and lentiviral vectors by transient transfection resulted in vector titers similar to those with A-MLVenv or VSV-G. In contrast to A-MLVenv particles, LCMV-GP pseudotypes could be efficiently concentrated by ultracentrifugation without loss of vector titer. Unlike the cell-toxic VSV-G, a stable retroviral packaging cell line constitutively expressing LCMV-GP could be established. Vectors pseudotyped with LCMV-GP efficiently transduced many cell lines from different species and tissues relevant for gene therapy. Transduction of human glioma cells was studied in detail. These cells are a major target for cancer gene therapy and were transduced more efficiently with LCMV-GP-pseudotyped vectors than with the generally used A-MLVenv particles. The high stability, low toxicity, and broad host range make LCMV-GP-pseudotyped vectors attractive for gene transfer applications. The recombinant LCMV-GP-pseudotyped vectors will also allow functional characterization of naturally occurring and recombinant LCMV-GP variants. PMID- 11773422 TI - In vivo assessment of gene delivery to keratinocytes by lentiviral vectors. AB - For skin gene therapy, introduction of a desired gene into keratinocyte progenitor or stem cells could overcome the problem of achieving persistent gene expression in a significant percentage of keratinocytes. Although keratinocyte stem cells have not yet been completely characterized and purified for gene targeting purposes, lentiviral vectors may be superior to retroviral vectors at gene introduction into these stem cells, which are believed to divide and cycle slowly. Our initial in vitro studies demonstrate that lentiviral vectors are able to efficiently transduce nondividing keratinocytes, unlike retroviral vectors, and do not require the lentiviral accessory genes for keratinocyte transduction. When lentiviral vectors expressing green fluorescent protein (GFP) were directly injected into the dermis of human skin grafted onto immunocompromised mice, transduction of dividing basal and nondividing suprabasal keratinocytes could be demonstrated, which was not the case when control retroviral vectors were used. However, flow cytometry analysis demonstrated low transduction efficiency, and histological analysis at later time points provided no evidence for progenitor cell targeting. In an alternative in vivo method, human keratinocytes were transduced in tissue culture (ex vivo) with either lentiviral or retroviral vectors and grafted as skin equivalents onto immunocompromised mice. GFP expression was analyzed in these human skin grafts after several cycles of epidermal turnover, and both the lentiviral and retroviral vector-transduced grafts had similar percentages of GFP-expressing keratinocytes. This ex vivo grafting study provides a good in vivo assessment of gene introduction into progenitor cells and suggests that lentiviral vectors are not necessarily superior to retroviral vectors at introducing genes into keratinocyte progenitor cells during in vitro culture. PMID- 11773423 TI - Adaptation of wild-type measles virus to tissue culture. AB - Measles has a host range restricted to humans and monkeys in captivity. Fresh measles virus (MV) isolates replicate readily in several human and simian B-cell lines but need a period of adaptation to other types of cells. The identification of CD46 and CD150 (SLAM) as cellular receptors for MV has helped to clarify certain aspects of the immunobiology of MV infections. We have examined the properties of an MV wild-type strain grown in the epithelial cell line Vero. After adaptation, this virus expressed high levels of both the viral glycoproteins (hemagglutinin and fusion protein) but did not induce fusion (syncytia). No changes in the amino acid sequence were found in either of the viral glycoproteins. Using several approaches, the Vero-adapted virus could not be shown to interact with CD46 either in the initiation or during the course of infection. The presence of human SLAM expressed in the Vero cells rapidly gave rise to fusion and lower yields of infectious virus. PMID- 11773424 TI - Comparison of gene transfer efficiencies and gene expression levels achieved with equine infectious anemia virus- and human immunodeficiency virus type 1-derived lentivirus vectors. AB - This report compares gene transfer efficiencies as well as durations and levels of gene expression for human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) lentiviral vectors in a variety of human cell types in vitro. EIAV and HIV vectors transduced equivalent numbers of proliferating and G1/S- and G2/M-arrested cells, and both had very low efficiencies of transduction into G0 arrested cells. Analysis of the levels of both the enhanced green fluorescent protein (EGFP) and mRNA demonstrated that the HIV-transduced cells expressed greater levels of EGFP protein and RNA than the EIAV-transduced cells. Measurements of vector-derived EGFP RNA half-lives were fourfold higher with the HIV vector than with the EIAV vector. Long-term culture of EIAV-transduced human cells showed a significant decrease in the number of cells expressing the transgene; however, no corresponding loss was found in EIAV-transduced equine cells. In contrast, only a moderate decrease in the number of transgene expressing cells was seen with the HIV vectors. Taken together, these results demonstrate that the EIAV vectors transduced human cells with efficiencies similar to those of the HIV vectors. However, our data indicate that transgene expression from EIAV vectors is limited by the instability of vector-derived RNA transcripts and silencing of the EIAV vectors over time. PMID- 11773425 TI - Sequence and genetic arrangement of the U(S) region of the monkey B virus (cercopithecine herpesvirus 1) genome and comparison with the U(S) regions of other primate herpesviruses. AB - The sequence of the unique short (U(S)) region of monkey B virus (BV) was determined. The 13 genes identified are arranged in the same order and orientation as in herpes simplex virus (HSV). These results demonstrate that the BV U(S) region is entirely colinear with that of HSV type 1 (HSV-1), HSV-2, and simian agent 8 virus. PMID- 11773426 TI - Kissing interaction between 3' noncoding and coding sequences is essential for porcine arterivirus RNA replication. AB - We used an infectious cDNA clone of porcine reproductive and respiratory syndrome virus (PRRSV) to investigate the presence of essential replication elements in the region of the genome encoding the structural proteins. Deletion analysis showed that a stretch of 34 nucleotides (14653 to 14686) within ORF7, which encodes the nucleocapsid protein, is essential for RNA replication. Strand specific reverse transcription-PCR analysis of viral RNA isolated from transfected BHK-21 cells revealed that this region is required for negative strand genomic RNA synthesis. The 34-nucleotide stretch is highly conserved among PRRSV isolates and folds into a putative hairpin. A 7-base sequence within the loop of this structure was suggested to base-pair with a sequence present in the loop of a hairpin located in the 3' noncoding region, resulting in a kissing interaction. Mutational analyses confirmed that this kissing interaction is required for RNA replication. PMID- 11773427 TI - Analysis of the disease potential of a recombinant retrovirus containing Friend murine leukemia virus sequences and a unique long terminal repeat from feline leukemia virus. AB - We have molecularly cloned a feline leukemia virus (FeLV) (clone 33) from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV proviruses from other cats with AML, contains an unusual structure in its U3 region upstream of the enhancer (URE) consisting of three tandem direct repeats of 47 bp. To test the disease potential and specificity of this unique FeLV LTR, we replaced the U3 region of the LTR of the erythroleukemia-inducing Friend murine leukemia virus (F-MuLV) with that of FeLV clone 33. When the resulting virus, F33V, was injected into newborn mice, almost all of the mice eventually developed hematopoietic malignancies, with a significant percentage being in the myeloid lineage. This is in contrast to mice injected with an F-MuLV recombinant containing the U3 region of another FeLV that lacks repetitive URE sequences, none of which developed myeloid malignancies. Examination of tumor proviruses from F33V-infected mice failed to detect any changes in FeLV U3 sequences other than that in the URE. Like F-MuLV-infected mice, those infected with the F-MuLV/FeLV recombinants were able to generate and replicate mink cell focus-inducing viruses. Our studies are consistent with the idea that the presence of repetitive sequences upstream of the enhancer in the LTR of FeLV may favor the activation of this promoter in myeloid cells and contribute to the development of malignancies in this hematopoietic lineage. PMID- 11773428 TI - Increased p50/p50 NF-kappaB activation in human papillomavirus type 6- or type 11 induced laryngeal papilloma tissue. AB - We have observed elevated NF-kappaB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-kappaB activity could be correlated with a reduced level of cytoplasmic IkappaBbeta and could be associated with the overexpression of p21(CIP1/WAF1) in papilloma cells. Increased NF-kappaB activity and cytoplasmic accumulation of p21(CIP1/WAF1) might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues. PMID- 11773429 TI - Learning and memory in transgenic mice modeling Alzheimer's disease. AB - Recent advances in behavioral analyses of transgenic mouse models of Alzheimer's disease (AD) are discussed, and their impact on our understanding of the molecular basis of cognitive impairment in AD is considered. Studies of the relationship between memory and A Beta in transgenic mice expressing the amyloid precursor protein (APP) and its variants suggest that aging promotes the formation of soluble A Beta assemblies mediating negative effects on memory. A significant component of memory loss in APP transgenic mice is apparently caused by soluble A Beta assemblies, but whether and how much of the dementia within individuals afflicted with AD is caused by these A Beta species is unclear. Future studies in composite transgenic mice developing amyloid plaques, neurofibrillary tangles, and other AD pathology may allow for the determination of the relative contribution of A Beta and non-A Beta components to dementia. PMID- 11773430 TI - Working memory for temporal and nontemporal events in monkeys. AB - This is the first report that introduces appropriate behavioral tasks for monkeys for investigations of working memory for temporal and nontemporal events. Using several behavioral tests, the study also shows how temporal information is coded during retention intervals in the tasks. Each of three monkeys was trained with two working memory tasks: delayed matching-to-sample of stimulus duration (DMS-D) and delayed matching-to-sample of stimulus color (DMS-C). The two tasks employed an identical apparatus and responses and differed only in the temporal and nontemporal attribute of the stimuli to be retained for correct performance. When a retention interval between the sample and comparison stimuli was prolonged, the monkeys made more incorrect responses to short samples in the DMS-C task, suggesting "trace decay" of memory for short stimuli. However, the same monkeys showed no such increase in incorrect responses to short samples in the DMS-D task, suggesting active coding of temporal information, that is, the length of stimulus duration, during the retention interval. When variable lengths of samples were presented with a fixed retention interval, the monkeys made more incorrect responses when length differences between short and long samples were small in the DMS-D task, but not in the DMS-C task. This suggests that the codes of working memory retained in the DMS-D task were not absolute (analogical) but rather were relative (categorical) and related to differences in the duration of the samples. PMID- 11773431 TI - Effect of age and level of cognitive function on spontaneous and exploratory behaviors in the beagle dog. AB - Cognitively characterized young and aged beagle dogs were administered six different spontaneous behavior tests, which provided measures of locomotion, exploration, and social interaction. Consistent with our previous findings, we obtained no overall effect of age on locomotion. We did find, however, that for the aged dogs locomotion correlated with level of cognitive function, being lowest in age-unimpaired dogs and highest in impaired dogs. Exploratory behavior, as measured by response to novelty, varied with age, with young dogs scoring the highest. Young dogs spent more time with novel toys and a person, responded more to a silhouette of a dog, and interacted more with a model dog compared to aged dogs. Among the aged dogs, age-unimpaired dogs spent the greatest amount of time sitting or standing beside a person whereas age-impaired dogs spent the most time reacting to a reflection in a mirror. The age-impaired dogs show undirected, stereotypical types of behavioral patterns. These differences in activity patterns may be linked to underlying age-associated neuropathology. PMID- 11773432 TI - Verbal and nonverbal emotional memory following unilateral amygdala damage. AB - The amygdala is involved in the normal facilitation of memory by emotion, but the separate contributions of the left and right amygdala to memory for verbal or nonverbal emotional material have not been investigated. Fourteen patients with damage to the medial temporal lobe including the amygdala (seven left, seven right), 18 brain-damaged, and 36 normal controls were exposed to emotional and neutral pictures accompanied by verbal narratives. Memory for both narratives and pictures was assessed with a free recall test 24 h later. Subjects with left amygdala damage failed to show the normally robust enhancement of memory for verbal and nonverbal emotional stimuli. The group with right amygdala damage showed the normal pattern of facilitation of memory by emotion for both verbal and nonverbal stimuli despite an overall reduction in memory performance. Furthermore, subjects with left amygdala damage were disproportionately impaired on memory for emotional narratives as compared with memory for emotional pictures. The latter finding offers partial support for a lateralized and material-specific pattern of the amygdala's contribution to emotional memory. PMID- 11773434 TI - Phosphorylation of the receptor for PTH and PTHrP is required for internalization and regulates receptor signaling. AB - We have previously shown that agonist-dependent phosphorylation of the PTH/PTHrP receptor occurs on its carboxyl-terminal tail. Using site-directed mutagenesis, phosphopeptide mapping, and direct sequencing of cyanogen bromide-cleaved fragments of phosphoreceptors, we report here that PTH-dependent phosphorylation occurs on the serine residues at positions 491, 492, 493, 495, 501, and 504, and that the serine residue at position 489 is required for phosphorylation. When these seven sites were mutated to alanine residues, the mutant receptor was no longer phosphorylated after PTH stimulation. The phosphorylation-deficient receptor, stably expressed in LLCPK-1 cells, was impaired in PTH-dependent internalization and showed an increased sensitivity to PTH stimulation; the EC(50) for PTH-stimulated cAMP accumulation was decreased by 7-fold. Furthermore, PTH stimulation of the phosphorylation-deficient PTH/PTHrP receptor caused a sustained elevation in intracellular cAMP levels. These data indicate that agonist-dependent phosphorylation of the PTH/PTHrP receptor plays an important role in receptor function. PMID- 11773435 TI - A distinct thyroid hormone response element mediates repression of the human cholesterol 7alpha-hydroxylase (CYP7A1) gene promoter. AB - We examined the molecular basis by which T3 regulates the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter. L-T3 decreased chloramphenicol acetyltransferase activity in hepatoma cells cotransfected with a plasmid encoding the T3 receptor (TR) alpha [NR1a1] and a chimeric gene containing nucleotides -372 to +61 of the human CYP7A1 gene fused to the chloramphenicol acetyltransferase structural gene. Deoxyribonuclease I footprinting revealed that recombinant TRalpha protected two regions in this segment of the human CYP7A1 gene promoter. In EMSAs, TRalpha bound to both regions. The binding was competed by oligonucleotides bearing an idealized TRalpha binding motif and abolished by mutation of these elements. In assays of promoter function, mutation of only one of the TRalpha binding sites blocked repression by T3. The results indicate that T3-dependent repression of human CYP7A1 gene expression is mediated via a novel site in the human CYP7A1 gene promoter. PMID- 11773433 TI - Hippocampal activations during repetitive learning and recall of geometric patterns. AB - Hippocampal activation is required for episodic memory. Encoding and retrieval of novel and memorable items have been related to different locations in the hippocampus; however, the data remain ambiguous. The application of a newly designed keyboard allowed investigation of brain activation during encoding and free immediate and delayed recall with functional magnetic resonance imaging (fMRI) in young healthy controls (n = 12). Because of the repetitive learning and recall conditions, an individual learning gradient was used to contrast neural activity at different individual levels of novelty. During learning, subjects were asked to memorize 10 geometric patterns requiring the establishment of intra item associations for memorization. After learning, subjects were asked to recall the items actively via the keyboard. Learning and recall were alternated five times. Delayed recall was scanned about 15 min after the fifth immediate recall condition without subjects having seen the items again. Left-sided anterior hippocampal activity was observed during conditions of initial learning as well as maximum recall. Neural activity during delayed recall did not reveal hippocampal responses and was characterized by a transition of neural activity from occipitoparietal regions to bilateral temporal cortices. We conclude that both lateralization and segregation depend on the specific relational characteristics of the stimuli requiring establishment of intra-item associations for encoding as well as retrieval. The absence of hippocampal activation during delayed recall together with the increase of lateral temporal involvement possibly corresponds with an emerging transition from episodic to long-term memory. PMID- 11773436 TI - Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene. AB - Mice devoid of all TRs are viable, whereas Pax8(-/-) mice, which lack the follicular cells producing T4 and T3 in the thyroid gland, die during the first weeks of postnatal life. A precise comparison between the two types of mutants reveals that their phenotypes are similar, but the defects in spleen, bone, and small intestine are more pronounced in Pax8(-/-) mice. This is interpreted as the result of a negative effect of the unliganded TR on thyroid hormone target genes expression in the Pax8(-/-) mutants. Pax8/TRalpha compound mutants can survive to adulthood, and the expression of target genes is partially restored. This demonstrates the importance of TRalpha aporeceptor activity in several aspects of postnatal development. PMID- 11773437 TI - RhoA activation promotes transformation and loss of thyroid cell differentiation interfering with thyroid transcription factor-1 activity. AB - Highly specialized cells, the thyrocytes, express a thyroid-specific set of genes for thyroglobulin (Tg), thyroperoxidase, and the transcription factors TTF-1, TTF 2, and Pax-8. The implication of the small GTPase RhoA in TSH-mediated proliferation of FRTL-5 rat thyroid cells has been previously demonstrated. To further analyze RhoA function in thyroid cell proliferation and differentiation patterns, we combined transient and stable transfection assays to express different mutant RhoA forms in FRTL-5 cells. Constitutively active RhoA (FRTL-5 RhoA QL cells) exhibited a fibroblast-like phenotype with organized actin fibers, whereas cells expressing the RhoA negative dominant phenotype (FRTL-5-RhoA N19 cells) present a rounded morphology and lose normal cytoskeletal architecture. In addition, expression of the constitutively active form of RhoA results in TSH independent proliferation and anchorage-independent growth and induces tumors when inoculated in nude mice. Interestingly, FRTL-5-RhoA QL cells express less Tg and TTF-1 than wild-type FRTL-5 (FRTL-5- vector) or FRTL-5-RhoA N19, suggesting a loss at the differentiation stage. This effect is mediated, at least in part, by a decrease in TTF-1 activity, since transient or stable expression of RhoA QL results in a reduction in the activity of the wild-type Tg promoter as well as an artificial promoter the activation of which depends exclusively on TTF-1. The similarity between RhoA effects and thyroid transformation by Ras suggests that RhoA may act as a downstream effector of Ras; in fact, the dominant negative RhoA N19 abolished the down- regulatory effect of Ras V12 over the Tg promoter. Taken together, these results show for the first time that active RhoA is able to transform FRTL-5 cells and that this effect is coupled to a loss of thyroid differentiation due to impaired TTF-1 activity. PMID- 11773438 TI - PRL modulates cell cycle regulators in mammary tumor epithelial cells. AB - PRL is essential for normal lobulo-alveolar growth of the mammary gland and may contribute to mammary cancer development or progression. However, analysis of the mechanism of action of PRL in these processes is complicated by the production of PRL within mammary epithelia. To examine PRL actions in a mammary cell-specific context, we selected MCF-7 cells that lacked endogenous PRL synthesis, using PRL stimulation of interferon-gamma-activated sequence-related PRL response elements. Derived clones exhibited a greater proliferative response to PRL than control cells. To understand the mechanism, we examined, by Western analysis, levels of proteins essential for cell cycle progression as well as phosphorylation of retinoblastoma protein. The expression of cyclin D1, a critical regulator of the G1/S transition, was significantly increased by PRL and was associated with hyperphosphorylation of retinoblastoma protein at Ser(780). Cyclin B1 was also increased by PRL. In contrast, PRL decreased the Cip/Kip family inhibitor, p21, but not p16 or p27. These studies demonstrate that PRL can stimulate the cell cycle in mammary epithelia and identify specific targets in this process. This model system will enable further molecular dissection of the pathways involved in PRL-induced proliferation, increasing our understanding of this hormone and its interactions with other factors in normal and pathogenic processes. PMID- 11773439 TI - A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of signal transducer and activator of transcription 5a and 5b by TC-PTP in nucleus. AB - In the present study we examined involvement of nuclear protein tyrosine phosphatase TC-PTP in PRL-mediated signaling. TC-PTP could dephosphorylate signal transducer and activator of transcription 5a (STAT5a) and STAT5b, but the apparent dephosphorylation activity of TC-PTP was weaker than that of cytosolic PTP1B 30 min after PRL stimulation in transfected COS-7 cells, whereas both STAT5a and STAT5b were dephosphorylated to the same extent by recombinant TC-PTP and PTP1B in vitro. Tyrosine-phosphorylated STAT5 was coimmunoprecipitated with substrate trapping mutants of TC-PTP, suggesting that STAT5 is a specific substrate of TC-PTP. These observations were further extended in mammary epithelial COMMA-1D cells stably expressing TC-PTP. A time-course study revealed that dephosphorylation of STAT5 by TC-PTP was delayed compared with that by cytosolic PTP1B due to nuclear localization of TC-PTP throughout PRL stimulation in mammary epithelial cells. Endogenous beta-casein gene expression and beta casein gene promoter activation in COS-7 cells were largely suppressed by TC-PTP wild type as well as catalytically inactive mutants, suggesting that stable complexes formed between STAT5 and TC-PTP in the nucleus. Taken together, we conclude that TC-PTP is catalytically competent with respect to dephosphorylation and deactivation of PRL-activated STAT5 in the nucleus. PMID- 11773440 TI - Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. AB - Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gbetagamma subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17beta-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERbeta, but not ERalpha, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP ribosylates and activates Galphas subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17alpha-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway. PMID- 11773441 TI - AR and ER interaction with a p21-activated kinase (PAK6). AB - A human protein termed p21-activated kinase 6 (PAK6), based on homology to the PAK family of serine/threonine kinases, was cloned as an AR interacting protein. PAK6 was a 75-kDa protein with a predicted N-terminal Cdc42/Rac interactive binding domain and a C-terminal kinase domain. PAK6 bound strongly to GTP-Cdc42 and weakly to GTP-Rac. In contrast to most PAKs, kinase activity was not stimulated by Cdc42 or Rac, but could be stimulated by AR binding. PAK6 interacted with the intact AR in a mammalian one-hybrid assay and bound in vitro, without ligand, to the hinge region between the AR DNA- and ligand-binding domains. PAK6 also bound to the ERalpha, and binding was enhanced by 4 hydroxytamoxifen. AR and ERalpha transcriptional activities were inhibited by PAK6 in transient transfections with episomal and integrated reporter genes. AR inhibition was not reversed by transfection with an activated Cdc42 mutant, Cdc42V12, which by itself also inhibited AR transactivation. Epitope-tagged PAK6 was primarily cytoplasmic in the absence or presence of AR and hormone. PAK6 transcripts were expressed most highly in brain and testis, with lower levels in multiple tissues including prostate and breast. PAK6 interaction provides a mechanism for cross-talk between steroid hormone receptors and Cdc42-mediated signal transduction pathways and could contribute to the effects of tamoxifen in breast cancer and in other tissues. PMID- 11773442 TI - ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. AB - Recent evidence supports the existence of a plasma membrane ER. In many cells, E2 activates signal transduction and cell proliferation, but the steroid inhibits signaling and growth in other cells. These effects may be related to interactions of ER with signal-modulating proteins in the membrane. It is also unclear how ER moves to the membrane. Here, we demonstrate ER in purified vesicles from endothelial cell plasma membranes and colocalization of ERalpha with the caveolae structural coat protein, caveolin-1. In human vascular smooth muscle or MCF-7 (human breast cancer) cell membranes, coimmunoprecipitation shows that ER associates with caveolin-1 and -2. Importantly, E2 rapidly and differentially stimulates ER-caveolin association in vascular smooth muscle cells but inhibits association in MCF-7 cells. E2 also stimulates caveolin-1 and -2 protein synthesis and activates a caveolin-1 promoter/luciferase reporter in smooth muscle cells. However, the steroid inhibits caveolin synthesis in MCF-7 cells. To determine a function for caveolin-ER interaction, we expressed caveolin-1 in MCF 7 cells. This stimulated ER translocation to the plasma membrane and also inhibited E2-induced ERK (MAPK) activation. Both functions required the caveolin 1 scaffolding domain. Depending upon the target cell, membrane ERs differentially associate with caveolin, and E2 differentially modulates the synthesis of this signaling-inhibitory scaffold protein. This may explain the discordant signaling and actions of E2 in various cell types. In addition, caveolin-1 is capable of facilitating ER translocation to the membrane. PMID- 11773444 TI - Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs. AB - Ligand-dependent interaction of nuclear receptors and coactivators is a critical step in nuclear receptor-mediated transcriptional regulation. TR-binding protein (TRBP) interacts with nuclear receptors through a single LXXLL motif. Evidence suggested that the sequences flanking the LXXLL motif in a number of coactivators determine receptor selectivity. We performed mutagenesis studies at residues adjacent to the TRBP LXXLL motif and identified S884 of TRBP at the -3 position of the LXXLL motif as a key residue for receptor selectivity. Analysis of in vitro and in vivo receptor interactions with TRBP suggested that S884 allowed selective interactions for ERbeta, TR, and RXR vs. ERalpha. Transient transfection studies further confirmed that the LXXLL-binding affinity correlates with TRBP transcriptional activity. Consistent with the structural modeling, an E380G substitution within ERalpha altered the binding to TRBP mutants, demonstrating the direct contact between TRBP S884 and ERalpha E380, which is a residue that distinguishes receptor subclasses. Furthermore, S884 can be phosphorylated by MAPK in vitro, an event that significantly altered the binding of TRBP to ER and suggests a potential mechanism for regulatory interaction. As the differential recruitment of TRBP to ERalpha and ERbeta may rely on S884, our finding provides insight into estrogen signaling and may lead to the development of therapeutic receptor-selective peptide antagonists. PMID- 11773445 TI - Functional association of PR and CCAAT/enhancer-binding protein beta isoforms: promoter-dependent cooperation between PR-B and liver-enriched inhibitory protein, or liver-enriched activatory protein and PR-A in human endometrial stromal cells. AB - Activation of the decidual PRL (dPRL) promoter, a major differentiation marker in human endometrial stromal (ES) cells, by cAMP is effected through the induction and binding of CCAAT/enhancer-binding protein-beta (C/EBPbeta) to two overlapping cognate response elements in the promoter region dPRL-332/-270. Progesterone is essential for decidualization and potently enhances cAMP-dependent dPRL promoter activity. We now demonstrate that both liganded PR isoforms, PR-A and PR-B, are capable of trans-activating the dPRL-332/-270 region. The absence of a palindromic progesterone response element (PRE) within this promoter region suggested cross-coupling between C/EBPbeta and PR in human ES cells. Physical interaction between these distinct transcription factors was confirmed by glutathione-S-transferase pull-down assays, demonstrating that both C/EBPbeta isoforms, the full-length activator liver-enriched activatory protein (LAP) and the truncated inhibitor liver-enriched inhibitory protein (LIP), can bind PR-B as well as PR-A in vitro. Transient transfection studies in primary ES cells were used to examine the consequences of PR and C/EBPbeta interaction on activation of their respective response elements. Activation of mouse mammary tumor virus promoter or a reporter construct containing two isolated palindromic PREs by liganded PR-B was synergistically enhanced by coexpression of LIP, but not LAP. In contrast, PR-A failed to trans-activate these constructs significantly regardless of the presence of either C/EBPbeta isoform. Conversely, LAP-dependent activation of the dPRL-332/-270 region or a reporter construct driven by a single C/EBPbeta response element was greatly enhanced by PR-A, but not PR-B, in a ligand-dependent manner. These observations reveal that PR and C/EBPbeta isoform ratios are important determinants of the cellular response to ovarian progesterone in the reproductive tract; the predominance of PR-A and LAP favors expression of C/EBPbeta-dependent genes, whereas PR-B and LIP cooperate in activating PRE-driven promoters. PMID- 11773443 TI - Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation. AB - E2 rapidly activates MAPK in breast cancer cells, and the mechanism for this effect has not been fully identified. Since growth factor-induced MAPK activation involves signaling via the adapter protein Shc (Src-homology and collagen homology) and its association with membrane receptors, we hypothesized that breast cancer cells utilize similar signaling mechanisms in response to E2. In the present study, we demonstrated that E2 rapidly induced Shc phosphorylation and Shc-Grb2 (growth factor receptor binding protein 2)-Sos (son of sevenless) complex formation in MCF-7 cells. Overexpression of dominant negative Shc blocked the effect of E2 on MAPK, indicating a critical role of Shc in E2 action. Using selective inhibitors, we also demonstrated that ERalpha and Src are upstream regulators of Shc. A rapid physical association between ERalpha and Shc upon E2 stimulation further evidenced the role of ERalpha on Shc activation. Mutagenesis studies showed that the phosphotyrosine binding and SH2 domains of Shc are required to interact with the activation function 1, but not activation function 2, domain of ERalpha. Using a glutathione-S-transferase-Shc pull-down assay, we demonstrated that this ERalpha-Shc association was direct. Biological consequences of this pathway were further investigated at the genomic and nongenomic levels. E2 stimulated MAPK-mediated Elk-1 transcriptional activity. Confocal microscopy studies showed that E2 rapidly induced formation of membrane ruffles, pseudopodia, and ERalpha membrane translocation. The E2-induced morphological changes were prevented by antiestrogen. Together our results demonstrate that ERalpha can mediate the rapid effects of E2 on Shc, MAPK, Elk-1, and morphological changes in breast cancer cells PMID- 11773446 TI - Pituitary, pancreatic and gut neuroendocrine defects in protein tyrosine phosphatase-sigma-deficient mice. AB - The expression of receptor protein tyrosine phosphatase sigma (PTPfinal sigma) is developmentally regulated in neuronal and neuroendocrine tissues. We have previously shown that mice deficient in PTPfinal sigma demonstrate nervous system abnormalities, pituitary hypoplasia, increased neonatal mortality (60%), and death from a wasting syndrome at 2-3 wk of age (38%). We have now examined the role of PTPfinal sigma on pituitary, pancreas and enteroendocrine cytodifferentiation, hormone production, and development. The adenohypophyses of PTPfinal sigma(-/-) mice were small and exhibited reduced GH and PRL immunoreactivity. Cells containing TSH, LH, FSH, ACTH, pituitary-specific POU homeodomain factor (Pit-1), ER, and steroidogenic factor 1 were found in normal proportions and distributions. The diminished expression of GH and PRL was not associated with apoptosis of somatotrophs or lactotrophs. Pit-1-positive TSH negative cells were detected, suggesting that impaired GH and PRL synthesis was not attributable to Pit-1 deficiency. In the knockout mice, pancreatic islets were hypoplastic with reduced insulin immunoreactivity, and there was also variable expression of gut hormones. Functionally, the GH deficiency was associated with hypoglycemia and death in the PTPfinal sigma(-/-) neonate and accordingly, ip administration of GH rescued the PTPfinal sigma(-/-) neonate and normalized the blood glucose. These data indicate that PTPfinal sigma plays a major role in differentiation and development of the neuroendocrine system. PMID- 11773447 TI - Hepatic nuclear factor-3 (HNF-3 or Foxa2) regulates glucagon gene transcription by binding to the G1 and G2 promoter elements. AB - Glucagon gene expression in the endocrine pancreas is controlled by three islet specific elements (G3, G2, and G4) and the alpha-cell-specific element G1. Two proteins interacting with G1 have previously been identified as Pax6 and Cdx2/3. We identify here the third yet uncharacterized complex on G1 as hepatocyte nuclear factor 3 (HNF-3)beta, a member of the HNF-3/forkhead transcription family, which plays an important role in the development of endoderm-related organs. HNF-3 has been previously demonstrated to interact with the G2 element and to be crucial for glucagon gene expression; we thus define a second binding site for this transcription on the glucagon gene promoter. We demonstrate that both HNF-3alpha and -beta produced in heterologous cells can interact with similar affinities to either the G1 or G2 element. Pax6, which binds to an overlapping site on G1, exhibited a greater affinity as compared with HNF-3alpha or -beta. We show that both HNF-3beta and -alpha can transactivate glucagon gene transcription through the G2 and G1 elements. However, HNF-3 via its transactivating domains specifically impaired Pax6-mediated transactivation of the glucagon promoter but had no effect on transactivation by Cdx2/3. We suggest that HNF-3 may play a dual role on glucagon gene transcription by 1) inhibiting the transactivation potential of Pax6 on the G1 and G3 elements and 2) direct activation through G1 and G2. PMID- 11773449 TI - Endocrine-related resources from the National Institutes of Health. PMID- 11773448 TI - Regulation of steroidogenesis and the steroidogenic acute regulatory protein by a member of the cAMP response-element binding protein family. AB - The mitochondrial phosphoprotein, the steroidogenic acute regulatory (StAR) protein, is an essential component in the regulation of steroid biosynthesis in adrenal and gonadal cells through cAMP-dependent pathways. In many cases transcriptional induction by cAMP is mediated through the interaction of a cAMP response-element binding protein (CREB) family member with a consensus cAMP response element (CRE; 5'-TGACGTCA-3') found in the promoter of target genes. The present investigation was carried out to determine whether a CRE-binding protein (CREB) family member [CREB/CRE modulator (CREM) family] was involved in the regulation of steroidogenesis and StAR protein expression. Transient expression of wild- type CREB in MA-10 mouse Leydig tumor cells further increased the levels of (Bu)2cAMP-induced progesterone synthesis, StAR promoter activity, StAR mRNA, and StAR protein. These responses were significantly inhibited by transfection with a dominant-negative CREB (A-CREB), or with a CREB mutant that cannot be phosphorylated (CREB-M1), the latter observation indicating the importance of phosphorylation of a CREB/CREM family member in steroidogenesis and StAR expression. The CREB/CREM-responsive region in the mouse StAR gene was located between -110 and -67 bp upstream of the transcriptional start site. An oligonucleotide probe (-96/-67 bp) containing three putative half-sites for 5' canonical CRE sequences (TGAC) demonstrated the formation of protein-DNA complexes in EMSAs with recombinant CREB protein as well as with nuclear extracts from MA-10 or Y-1 mouse adrenal tumor cells. The predominant binding factor observed with EMSA was found to be the CREM protein as demonstrated using specific antibodies and RT-PCR analyses. The CRE elements identified within the 96/-67 bp region were tested for cAMP responsiveness by generating mutations in each of the CRE half-sites either alone or in combination. Although each of the CRE sites contribute in part to the CREM response, the CRE2 appears to be the most important site as determined by EMSA and by reporter gene analyses. Binding specificity was further assessed using specific antibodies to CREB/CREM family members, cold competitors, and mutations in the target sites that resulted in either supershift and/or inhibition of these complexes. We also demonstrate that the inducible cAMP early repressor markedly diminished the endogenous effects of CREM on cAMP-induced StAR promoter activity and on StAR mRNA expression. These are the first observations to provide evidence for the functional involvement of a CREB/CREM family member in the acute regulation of trophic hormone-stimulated steroidogenesis and StAR gene expression. PMID- 11773450 TI - Diversity within the CLC chloride channel family involved in inherited diseases: from plasma membranes to acidic organelles. PMID- 11773451 TI - Human Schistosoma mansoni-associated glomerulopathy in Brazil. PMID- 11773452 TI - Dismal long-term survival of dialysis patients after acute myocardial infarction: can we alter the outcome? PMID- 11773453 TI - Omega-3 fatty acids in ESRD: should patients with ESRD eat more fish? PMID- 11773454 TI - Phosphate binders in uraemia: pharmacodynamics, pharmacoeconomics, pharmacoethics. PMID- 11773455 TI - Influencing the inflammatory response of haemodialysis patients by cytokine elimination using large-pore membranes. PMID- 11773456 TI - Which is the preferred vascular access in diabetic patients? A view from Europe. PMID- 11773457 TI - Intracranial hypertension in acute liver failure. PMID- 11773458 TI - The epidemiology of end-stage renal disease in Iran in an international perspective. AB - INTRODUCTION: The epidemiology of end-stage renal disease (ESRD) and renal replacement therapy (RRT) is under continuous evolution all over the world. We report here the epidemiological analysis of ESRD and RRT in Iran and discuss it against the background of the international situation. METHODS: This epidemiological report is based on data from centre questionnaires which were collected in Iran from 1997 onwards, with a response rate of 100%. RESULTS: The prevalence/incidence of RRT patients were 238/49.9 p.m.p. in the year 2000. Haemodialysis and kidney transplantation were the most common RRT modalities, accounting for 53.7% and 45.5% of prevalent RRT patients, respectively. The proportion treated by peritoneal dialysis was very low (<1%). Home haemodialysis was not performed. The majority of haemodialysis centres used synthetic membranes (70%) and 100% of the sessions were performed using acetate as a buffer; 42.5% of haemodialysis patients were treated with a twice-weekly regimen, whilst 49.6% were on the standard thrice-weekly regimen. The majority of RRT patients in Iran were young to middle aged. The great majority of renal allografts came from living donors (mainly unrelated to recipients). The main renal diseases leading to ESRD were diabetes and hypertension. The third most common category was "cause unknown". CONCLUSION: The epidemiology of RRT in Iran is characterized by: (i) young patient age (younger than the international average); (ii) high proportion of patients receiving renal allograft; (iii) use of living-unrelated donors as the major source of renal allografts. PMID- 11773459 TI - An overview of morbidity and mortality in patients with acute renal failure due to crush syndrome: the Marmara earthquake experience. AB - BACKGROUND: On August 17, 1999 a major earthquake hit the most densely populated area at the eastern end of the Marmara Sea in northwestern Turkey. The number of documented cases of acute renal failure (ARF) following this event exceeded all similar cases previously reported for any single earthquake. The aim of this report was to provide an overview of the morbidity and mortality of all documented patients with ARF, due to crush injury, that were treated in hospitals with dialysis units following the Marmara earthquake. METHODS: Special questionnaires were sent out to all hospitals with dialysis units known to have admitted earthquake victims with ARF and related crush injuries. Responses to questionnaires from the Turkish Society of Nephrology (TSN) Task Force were collected from 35 hospitals in October 1999. We retrospectively evaluated patients, clinic and laboratory findings, surgical interventions, and frequency and duration of dialysis. Patients who died before or on admission and those with prior chronic renal disease were excluded from the study. RESULTS: A total of 639 patients (291 female and 348 male) with ARF due to crush injury were hospitalized in 35 hospitals. The mean age was 31.6+/-14.7 years and 71.1% were young adults within the range of 16-45 years. 477 patients (74.6%) received one or more dialysis treatments, 162 patients were not dialysed, 15 patients died before dialysis could be instituted, and 147 patients recovered without dialysis treatment. 340 patients were oliguric on admission. The most important abnormalities related to ARF as a result of crush injury morbidity, were oliguria (53.2%), uraemia (94%), high creatinine levels (87%), hyperkalaemia (42%), hyperphosphataemia (63%), hypocalcaemia (83%), and high creatinine phosphokinase levels (73 %). 512 patients had a total of 790 extremity injuries. Eighty-three patients (12.9%) had fractures of the extremities and non-extremity fractures were observed in 59 (9.2%) patients. 323 fasciotomies were performed. Thoracic and abdominal trauma was observed in 110 patients (17.2%). Infection and sepsis were observed in 223 (34.9%) and 121 (18.9%) patients, respectively. Haematologic abnormalities were observed in 197 patients (33%) including 116 with Htc < or =30%. There were pulmonary problems in 96 patients (15%), cardiovascular problems in 198 patients (30.9%), gastrointestinal problems in 23 (3.16%), neurologic problems in 43 (6.7%), and psychiatric problems in 7 (1%) patients. Ninety-seven of the 639 patients with ARF as a result of crush injury died (15.2%), and mortality rates were 17.2 and 9.3% in dialysed and non-dialysed patients, respectively. Findings significantly associated with mortality were sepsis, thrombocytopenia, disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and abdominal and thoracic traumas. CONCLUSIONS: We conclude that in cases of severe disasters such as major earthquakes, patients should be rapidly transferred to undamaged peripheral general hospitals. When proper dialysis and intensive care facilities together with around the clock dedicated human effort are available, crush injury-related ARF patients have a lower mortality. Mortality, when it occurs, is mainly associated with thoracic and abdominal trauma and medical problems such as DIC and/or ARDS/respiratory failure, often in conjunction with sepsis. PMID- 11773461 TI - Transmembrane signalling in human monocyte/mesangial cell co-cultures: role of cytosolic Ca(2+). AB - BACKGROUND: Adhesion of monocytes triggers apoptosis, cytotoxicity, cytokine release, and later proliferation of cultured human mesangial cells (HMC). In the search for transmembrane signals transducing the interaction of HMC adhesion molecules with leukocyte counterreceptors, we measured variations of cytosolic Ca(2+) ([Ca(2+)](i)) in HMC and monocytes of the U937 cell line during 6-h co cultures. METHODS: Monolayer cultures of HMC and suspensions of U937 cells were loaded with the fluoroprobe fura 2-AM and subsequently co-cultured for 6 h while separately monitoring by microfluorometry the Ca(2+)-dependent 500 nm fluorescent emission of each cell line at fixed intervals upon excitation at 340/380 nm. RESULTS: U937 and peripheral blood monocyte adhesion was followed in HMC by a slow, progressive rise of [Ca(2+)](i) from basal levels of 96+/-9 nM to 339+/-54 at 60 min and 439+/-44 nM at 3 h. The [Ca(2+)](i) elevation reached a steady state thereafter, while parallel monolayers incubated with control media maintained resting levels throughout the co-culture with stable fluoroprobe retention. Receptor sensitivity to vasoconstrictor agents, including compounds not released by monocytes, such as angiotensin II, was rapidly downregulated in HMC co-cultured with U937 cells. No [Ca(2+)](i) changes could be elicited by the octapeptide or by the TxA(2) analogue, U-46619, as early as 30 min after exposure to U937 cells. No [Ca(2+)](i) changes were observed in U937 cells throughout the co-culture. Conditioned media from monocytes and from co-cultured HMC+U937 cells had no effect on [Ca(2+)](i) of HMC. Ca(2+) entry leading to fura 2 saturation was still inducible by Ca(2+) ionophores, such as ionomycin and 4-Br-A23187, which also inhibited the responses to vasoconstrictors. Ca(2+)-free solutions prevented the [Ca(2+)](i) rise as well as subsequent receptor inactivation, implicating Ca(2+) influx through store-operated Ca(2+) channels (SOC), a major pathway for Ca(2+) entry in these cultured cells. Ca(2+) influx was confirmed by Mn(2+)-quenching of fura 2. CONCLUSIONS: In HMC, early changes in [Ca(2+)](i) signal for monocyte adhesion in a co-culture model of glomerular inflammation. This signalling mechanism may mediate the functional responses elicited in glomerular cells by leukocytes, including downregulation of receptors for vasoactive agents. PMID- 11773462 TI - Enzymatically deglycosylated human IgA1 molecules accumulate and induce inflammatory cell reaction in rat glomeruli. AB - BACKGROUND: Previously, we have been able to isolate IgA1 from IgA nephropathy (IgAN) patients, that could accumulate in rat glomeruli (glomerulophilic IgA1). The 'glomerulophilic IgA1' was determined to be under-O-glycosylated in its hinge region, suggesting that under-O-glycosylation in the IgA1 hinge region plays a role in its glomerular deposition in IgAN. To confirm this, the accumulation of enzymatically under-glycosylated IgA1 in rat kidney was examined. METHODS: Human IgA1 was isolated from healthy individuals by Jacalin-affinity chromatography. Desialylated (deS IgA1) or further degalactosylated IgA1 (deS/deGal IgA1) molecules were then prepared using neuraminidase and beta-galactosidase. Two or five mg of IgA1 were injected into the left renal artery of Wistar rats. The rats were sacrificed at various time intervals (3, 9, 24 h) and the perfused part of the renal cortex was removed for immunofluorescence and for light and electron microscopy. RESULTS: Distinct amounts of deS IgA1 and deS/deGal IgA1 were observed in rat glomeruli. On the other hand, untreated IgA1 molecules (native IgA1) did not show any obvious accumulation. In rats injected with under glycosylated IgA1, accumulation of polymorphonuclear cells (PMN) was also observed. CONCLUSIONS: These results confirmed that under-glycosylation of IgA1 played an important role in the glomerular accumulation of IgA1, which was followed by infiltration of PMN into glomeruli. PMID- 11773463 TI - C5b-9 and adhesion molecules in human idiopathic membranous nephropathy. AB - BACKGROUND: Cellular immune responses and C5b-9 seem to play an important role in the pathogenesis and progression of idiopathic membranous nephropathy (IMN). The aim of the study was to investigate the role of C5b-9 and adhesion molecules in the pathogenesis of the disease. METHODS: The clinical and pathological data of 35 patients with biopsy-proven IMN were correlated with immunohistochemical findings using monoclonal antibodies against T lymphocytes, monocytes/macrophages (MM), HLA-DR antigens, C5b-9, and adhesion molecules such as alpha3beta1, LFA 1beta, and ICAM-1. RESULTS: In the glomeruli, C5b-9 deposits showed a significant correlation with the intensity of IgG and C3 deposition. The stage of the disease had a significant negative relationship with the glomerular alpha3beta1 expression. In the tubulointerstitium (TIN), the number of HLA-DR(+) cells was highly correlated with the numbers of total T lymphocytes, MM, and LFA-1beta(+) cells, as well as with the percentage of tubules with C5b-9 deposits. The extent of ICAM-1 expression in the TIN was significantly correlated with the numbers of interstitial MM, HLA-DR(+), and LFA-1beta(+) cells, as well as with the extent of tubular C5b-9 deposition. The severity of tubular atrophy and interstitial fibrosis had a relationship with the numbers of total T lymphocytes, MM, HLA DR(+), and LFA-1beta(+) cells and with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Serum creatinine (Scr) was highly correlated with the numbers of interstitial total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells. Moreover, Scr had a significant relationship with the severity of tubular atrophy and interstitial fibrosis, as well as with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Proteinuria was significantly correlated with the extent of tubular alpha3beta1 expression. CONCLUSIONS: In IMN, C5b-9 formation may be secondary to IgG and C3 deposition. Proteinuria may contribute to the TIN damage by altering the expression of alpha3beta1 integrins in tubular cells. De novo ICAM-1 and C5b-9 expression within the TIN as well as the activated interstitial cells may be important factors leading to renal damage and renal function impairment. PMID- 11773464 TI - Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives. AB - BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis in the world. Up to 30% of patients can progress to end-stage renal disease (ESRD) in 10 years. METHODS: We studied 168 Chinese patients with IgA nephropathy followed for an average of 7.4 years in our hospital and tried to identify the clinical and pathological data that were associated with the prognosis of the disease. Clinical features at the time of renal biopsy were reviewed. Severity of histological involvement was scored semi-quantitatively as grade 1-3. RESULTS: There was a female preponderance in our cohort of patients (male:female ratio 1:1.5). The average age at biopsy was 32.9+/-10.0 years. Forty-seven of the 168 patients (28.0%) were hypertensive and 47 of 136 patients (34.6%) had a family history of hypertension. A high histological grade of IgA nephropathy was associated with hypertension at presentation, family history of hypertension, a higher serum creatinine, total cholesterol and 24-h urine protein excretion, and a lower serum albumin level. During the follow-up period, four patients died and another 24 progressed to ESRD. The renal survival was 92.0% at 1 year, 87.5% at 5 years and 81.8% at 10 years. With univariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation (plasma creatinine >120 micromol/l), high cholesterol, proteinuria >1 g/day and high histological grading were associated with poor prognosis. With multivariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation, proteinuria >1 g/day and histological grading were independent predictors of renal survival. The relative risks of renal failure for patients were 9.60 (95% confidence interval 4.02-22.92) with hypertension, 1.56 (1.16-2.02) with a family history of hypertension, 15.38 (6.40-36.93) with renal impairment and 5.93 (3.07-11.46) with every increase of one histological grade. Male patients did not show a more adverse outcome compared with females. CONCLUSIONS: Our results suggest that renal biopsy remains useful, even in clinically trivial disease, because of its distinct value in prognosis and risk stratification. The long-term prognosis of IgA nephropathy in Chinese patients is guarded. The prognostic importance of family history of hypertension has not been widely recognized and requires further study. PMID- 11773466 TI - Alport syndrome associated with diffuse leiomyomatosis: COL4A5-COL4A6 deletion associated with a mild form of Alport nephropathy. AB - BACKGROUND: The X-linked Alport syndrome (AS) is an inherited nephropathy due to mutations in the COL4A5 gene, encoding the alpha5 chain of type IV collagen, a major component of the glomerular basement membrane (GBM). Here, we report a new kindred with the rare association of X-linked AS and diffuse leiomyomatosis (DL), which is a tumourous process involving smooth muscle cells of the oesophagus, the tracheobronchial tree and, in females, the genital tract. For this syndrome, an almost constant association of large COL4A5 rearrangements with a severe juvenile form of nephropathy has been described for male patients. METHODS: DNA rearrangement at the COL4A5-COL4A6 locus was studied in several members of this family using polymerase chain reaction and pulsed field gel electrophoresis. Furthermore, immunohistochemical staining of tumour and skin samples was performed. RESULTS: The affected patients in this family carry a 120 kb deletion by which the COL4A5 exon 1 and COL4A6 exons 1, 1', and 2 are removed. Immunohistochemical investigation of a skin biopsy of an affected male patient confirmed the absence of both the alpha5 and the alpha6 chains of type IV collagen in the basement membrane of the skin. Surprisingly, both affected male patients had a rather mild renal phenotype. CONCLUSIONS: This report shows that, contrary to what has been reported to date, patients suffering from AS associated with DL can be associated with a late onset renal failure (adult) form of nephropathy. PMID- 11773467 TI - Novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common disease in China. The major gene responsible for ADPKD, PKD1, has been fully characterized and shown to encode an integral membrane protein, polycystin 1, which is thought to be involved in cell-cell and cell-matrix interaction. Until now, 82 mutations of PKD1 gene have been reported in European, American, and Asian populations. However, there has been no report on mutations of the PKD1 gene in a Chinese population. METHODS: Eighty Chinese patients in 60 families with ADPKD were screened for mutations in the 3' region of the PKD1 gene using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA-sequencing techniques. RESULTS: Three mutations were found. The first mutation is a 12593delA frameshift mutation in exon 45, and the polycystin change is 4129WfsX4197, 107 amino acids shorter than the normal polycystin (4302aa). The second mutation is a 12470InsA frameshift mutation in exon 45, producing 4088DfsX4156, and the predicted protein is 148 amino acids shorter than the normal. The third one is a 11151C-->T transition in exon 37 converting Pro3648 to Leu. In addition, nine DNA variants, including IVS44delG, were identified. CONCLUSIONS: Three mutations in Chinese ADPKD patients are described and all of them are de novo mutations. Data obtained from mutation analysis also suggests that the mutation rate of the 3' single-copy region of PKD1 in Chinese ADPKD patients is very low, and there are no mutation hot spots in the PKD1 gene. Mutations found in Chinese ADPKD patients, including nucleotide substitution and minor frameshift, are similar to the findings reported by other researchers. Many mutations of the PKD1 gene probably exist in the duplicated region, promoter region, and the introns of PKD1. PMID- 11773468 TI - Microalbumin measurement alone or calculation of the albumin/creatinine ratio for the screening of hypertension patients? AB - BACKGROUND: Spot urine sampling seems to be a reliable screening method for the detection of microalbuminuria in hypertensive patients. It remains unclear whether microalbumin measurement alone or calculation of the albumin/creatinine ratio (ACR) are more reliable for the detection of microalbuminuria in non selected hypertensive patients. METHODS: Following collection of a spot, midstream urine sample, urine was collected for 24 h for the measurement of microalbumin in 264 hypertensive patients. We compared microalbumin concentration in the spot urine with microalbumin measured in the 24-h urine sample and examined the utility of the ACR in evaluating microalbuminuria in hypertensive patients. Pathologic microalbuminuria was assumed when the microalbumin concentration exceeded 30 mg/l in the 24-h urine sample. Diagnostic performance is expressed in terms of specificity, sensitivity, positive (PPV) and negative predictive value (NPV), and area under receiver operating characteristics curve (AUC). RESULTS: A total of 47 samples (17.8%) showed pathologic microalbuminuria in the 24-h urine sample. The diagnostic performance expressed as AUC was 0.94 (95% CI 0.90-0.98) for microalbumin measurement alone and 0.94 (95% CI 0.89-0.97) for ACR. The PPV and NPV were 44.2 and 97.9% for microalbumin measurement alone. ACR revealed a PPV of 29.3% and a NPV of 96.2% for males and 42.9 and 98% for females, if a cut-off value of 2.5 mg/mmol for males and of 4.0 mg/mmol for females was used. CONCLUSIONS: The ACR did not provide any advantage compared with microalbumin measurement alone, but requires an additional determination of creatinine and the use of gender-specific cut-off values. Therefore, measurement of microalbuminuria alone in the spot urine sample is more convenient in daily clinical practice and should be used as the screening method for hypertensive patients. PMID- 11773469 TI - Health profiles and health preferences of dialysis patients. AB - BACKGROUND: Health-related quality of life (HRQOL) of haemodialysis (HD) and peritoneal dialysis (PD) patients has been assessed with health profiles and health preferences methods. Few studies have used both types of HRQOL instruments. The main objective of this study was to assess the relationship between information from the two types of HRQOL instruments in dialysis patients. METHODS: We interviewed 135 patients, using two health profiles (Short Form 36 and EuroQol/EQ-5D) and two health preferences methods (Standard Gamble and Time Trade Off). Socio-demographic, clinical, and treatment-related background data were collected from patient charts and during the interview. Relationships between the outcome measures were assessed with Pearson correlation coefficients. Multiple regression models were used to study the relationship of HRQOL outcomes to background variables. RESULTS: The HRQOL of dialysis patients as measured with health profiles was severely impaired. The health preferences scores were higher (0.82-0.89) than scores previously reported in the literature. Correlations between health profiles and health preferences were poor to modest. HRQOL outcomes were poorly explained by background characteristics. Differences between HD and PD groups could not be demonstrated. CONCLUSIONS: Health profiles and health preferences represent different aspects of HRQOL. An impaired health status may not be reflected in the preference scores. Coping strategies and other attitudes towards health may affect the preference scores more than they influence health profile outcomes. The added value of health preferences methods in clinical research is limited. PMID- 11773470 TI - Psychosocial predictors of non-compliance in haemodialysis and peritoneal dialysis patients. AB - BACKGROUND: Non-compliance with prescribed therapy significantly impacts dialysis patient care and outcomes. The underlying psychosocial issues leading to non compliance are not well understood, especially in peritoneal dialysis (PD) patients. METHODS: A multicentre cohort of 119 haemodialysis (HD) patients and 51 PD patients was studied. In-person interviews were conducted with patients and clinical and laboratory data were obtained from medical records. Missed and shortened dialysis treatments/sessions and excessive serum phosphate values provided indicators of non-compliance. Patients' perceived health status, perceived self-health care, depression, perceived control over future health, social support, and disease-specific perceived quality of life were measured, along with current smoking status. Associations of predictor variables with non compliance indicators were examined in univariate and multivariable analyses. RESULTS: Approximately one-third of both HD and PD patients were non-compliant on at least one indicator. Logistic regression models identified a significant association between smoking and each non-compliance indicator. Patient age (younger) also predicted missed treatments. Perceived (negative) effects of kidney disease on daily life, and (decreased) perceived control over future health also predicted shortened treatments. No significant association was found between dialysis modality (HD vs PD) and non-compliance. CONCLUSION: Smoking, one marker of priority placed on health status, and intrusiveness/control issues should be addressed in intervention efforts to improve compliance in patients treated by HD and PD. PMID- 11773471 TI - Favourable long-term outcome by repeated percutaneous coronary revascularization in diabetic haemodialysis patients. AB - BACKGROUND: Diabetic haemodialysis patients have a high prevalence of coronary events and very high mortality rates. Percutaneous coronary intervention has become a well-established and routine procedure for coronary revascularization. This study investigated the long-term outcome of multiple repeated interventions in diabetic haemodialysis patients with coronary artery disease. METHODS: A retrospective study compared 37 type II diabetic haemodialysis patients with coronary artery disease and 26 non-diabetic patients matched for age, angiographic morphology, and devices of percutaneous intervention. All patients had undergone successful percutaneous intervention prior to enrollment. Percutaneous interventions were repeated in the event of restenosis or the development of a de novo lesion. RESULTS: Diabetic and non-diabetic patients were similar in terms of the number of follow-up angiograms (2.3+/-1.6 vs 2.4+/ 1.5/patient) and interventions (2.2+/-1.4 vs 2.2+/-1.5/patient), incidence of target lesion revascularization (85 vs 82%), and number of de novo lesions (15 vs 17%). The cumulative survival rates after the initial percutaneous intervention were similar in the groups (42% vs 31% at 80 months). Cardiac death occurred in 33% of diabetic patients and 42% of non-diabetic patients. Repeated intervention (regression coefficient=16.0, P<0.001) and a lower left ventricular ejection fraction (regression coefficient=-12.9, P=0.047) were determined for the important clinical factors associated with the survival duration after initial coronary intervention. CONCLUSIONS: Multiple repeated percutaneous interventions reduce the long-term mortality of diabetic and non-diabetic haemodialysis patients with coronary artery disease similarly. Multiple repeated percutaneous coronary interventions are a viable option for controlling myocardial ischaemia and improving the long-term outcome in high-risk diabetic haemodialysis patients. PMID- 11773472 TI - Ionic dialysance vs urea clearance in the absence of cardiopulmonary recirculation. AB - BACKGROUND: Several studies have shown a slight discrepancy between ionic dialysance (D) and dialyser urea clearance (UK), even in the absence of access recirculation. As it has been suggested that this discrepancy could be due to the cardiopulmonary recirculation, we studied the relationship between these two parameters in a particular dialysis setting without cardiopulmonary recirculation. METHODS: Paired measurement of urea clearance and ionic dialysance were performed in five patients without arterio-venous access who were dialysed via an internal jugular vein twin catheter. Fifty paired measurements were used for statistical analysis. Vascular access recirculation was assessed by an ultrasound dilution technique. The measured value of ionic dialysance was corrected (D(0)) for the effect of vascular access recirculation and was compared with instant urea clearance calculated from the dialysate side. RESULTS: The difference between the paired measurements of D(0) and UK (n=50) was equal to 0.6+/-16.9 ml/min (NS). With a statistical power of 90% and taking into account this standard deviation, this study might have shown a difference of at least 10.9 ml/min. The correlation was highly significant (P<0.0001). The discrepancy of the two parameters varied with dialysis efficiency, with a decreasing D(0):UK ratio for the higher dialysis efficiency. CONCLUSIONS: Compared with our previous results obtained in patients dialysed on arterio-venous access and performed with similar methods, the relationship between D(0) and UK is modified. This difference between D(0) and UK gets lower in patients dialysed on central catheters and this variance is in accordance with that expected when the influence of the cardiopulmonary recirculation on the measurement of ionic dialysance is taken into account. The limits of agreement (+/-2 SD) between D(0) and UK (+/-34 ml/min, Bland-Altman analysis) were higher than expected and raised questions about the accuracy of the measurement of each parameter via a central venous catheter. PMID- 11773473 TI - Initial survival advantage of peritoneal dialysis relative to haemodialysis. AB - BACKGROUND: The influence of dialysis modality on prognosis is controversial. In the absence of randomized trials, epidemiological investigations present the best method for studying the problem. METHODS: 4568 haemodialysis (HD) and 2443 peritoneal dialysis (PD) records in 4921 dialysis patients treated between 1990 and 1999 were retrieved from the Danish Terminal Uremia register in order to determine the influence of dialysis form on prognosis. The register is national, comprehensive, and incident. RESULTS: Factors reducing survival included age, cardiovascular disease, malignancy, lung disease, diabetes, alcoholism, haematological disease, but not sex or hypertension. Transplant non-candidacy was associated with an adjusted relative risk of 4.7 (CI 4.0-5.6). PD mortality relative to HD (after correction for comorbidity and transplant candidacy) was 0.65 (CI 0.59-0.72, P<0.001) on an "as treated" and "history" analysis and 0.86 (CI 0.78-0.95, P<0.01) on an intention-to-treat (ITT) analysis. The difference was confined to the first 2 years of dialysis. Change in dialysis modality was associated with increased mortality, and change from PD to HD with an accelerated mortality for the first 6 months. This was presumably due to the transfer of sick PD patients, but did not explain the difference. The relative advantage of PD was lower for diabetic patients, where it was not significant on ITT analysis. Dialysis prognosis improved by 14% during the period, with similar results for HD and PD patients. PD patients who were subsequently transplanted had a significantly shorter time to onset of graft function (3.5 vs 5.1 days, P<0.05). CONCLUSIONS: These results show a survival advantage for PD during the first 2 years of dialysis treatment. This may be due to unregistered differences in comorbidity at the start of treatment, or may be causal, possibly due to better preservation of residual renal function. The study lends credence to the "integrative care" approach to uraemia, where patients are started on PD and transferred to HD when PD related mortality increases. PMID- 11773474 TI - Incidence and clinical significance of nasal and pericatheter colonization by Gram-negative bacteria among patients undergoing chronic peritoneal dialysis. AB - BACKGROUND: Nasal and pericatheter colonization by Staphylococcus aureus portends an increased risk of peritonitis and exit-site infection for peritoneal dialysis (PD) patients. The aim of the present study was to examine the incidence of colonization by other peritoneal pathogens, and more specifically by Gram negative bacteria (GNB), among PD patients, and to disclose its potential correlation with PD-related infections. METHOD: Over a 3-year period, we prospectively screened 152 PD patients and 99 partners every other month for nasal and pericatheter bacterial colonization (total follow-up for patients 3182 months). We performed 1089 studies in patients and 561 in partners. RESULTS: Although S. aureus and coagulase-negative Staphylococcus spp. predominated both in patients and partners, we recovered GNB from 15.8% (nares) and 22.4% (pericatheter) of the patients and from 29.3% of the partners. Most isolations of GNB were transient and only 7.2% of the patients and 7.1% of the partners had the same GNB isolated in at least two controls from the same sampling site. Older age, male gender, longer follow-up on PD, previous immunosuppressive therapy, low socioeconomic conditions, and a high global incidence of peritonitis were predictive of colonization by GNB. Previous pericatheter mupirocin therapy was also associated with later colonization by GNB. Nasal or pericatheter colonization by bacteria other than S. aureus, particularly GNB, had a poor predictive power for PD-related infections. CONCLUSION: Nasal and pericatheter bacterial colonization is protean in PD patients and their partners, and includes the significant presence of potentially pathogenic GNB. Colonization by GNB was not clearly associated with an increased risk of peritonitis or exit-site infection in these patients. PMID- 11773475 TI - Segmental infarction with graft dysfunction: an emerging syndrome in renal transplantation? AB - BACKGROUND: Segmental allograft infarction is a poorly characterized complication following renal transplantation. The present study was undertaken with the goal of defining the incidence, clinical characteristics, pathogenesis, and prognosis of this entity. METHODS: A retrospective study was performed, reviewing the renal scans performed on all renal transplant recipients at our institution, from January 1997 to January 2000. Segmental infarction was diagnosed on the basis of a significant elevation in lactate dehydrogenase (>500 U/l) together with a photopenic perfusion defect. In these patients, graft characteristics, operative details, clinical course, and long-term outcomes were evaluated. RESULTS: Segmental infarction was identified in 13 of 277 consecutive renal transplant recipients (4.7%). In nine recipients the onset of infarction occurred within 24 h after transplantation. All received marginal grafts, and in five recipients the transplant operation was complicated by major blood loss. Eight of these recipients exhibited primary non-function, or developed dialysis-dependent renal failure after the onset of infarction. In four patients, the onset of infarction occurred after 24 h (35 h to 10 days). One recipient demonstrated primary non function, and renal function deteriorated after the onset of infarction in the remaining three. Overall, long-term graft function was impaired. Two allografts never functioned, and six recipients had nadir creatinine clearances below 60 ml/min. CONCLUSIONS: The pathogenesis of segmental infarction appears to be multi factorial, reflecting the combination of an initiating anatomic lesion and potentiating thrombogenic milieu. Segmental infarction typically occurs in the early postoperative period, and prompt diagnosis is difficult to obtain. In view of this, prophylactic heparin may be warranted for those at highest risk. There was no correlation between the infarct area and the graft function, and the long term graft function is compromised out of proportion to the extent of parenchymal loss. This finding highlights the role of predisposing factors, particularly marginal graft quality, in determining the functional outcome. Segmental infarction may be more frequently encountered as cadaveric organ shortages encourage greater use of marginal donor kidneys. PMID- 11773476 TI - Severe evolution of chronic hepatitis C in renal transplantation: a case control study. AB - BACKGROUND: To evaluate the impact of kidney transplantation on histopathological progression of hepatitis C virus (HCV)-related liver disease. METHODS: In a retrospective study, 28 HCV-positive renal transplant patients, who underwent two sequential liver biopsies with a mean of 7.1+/-4.0 years, were compared with 28 matched immunocompetent controls. RESULTS: According to the Metavir score, the initial and final activity scores (from 0 to 3) increased from 0.2+/-0.4 to 1.4+/ 1.1 (P<0.001) and those of fibrosis (from 0 to 4) from 0.5+/-0.5 to 2.0+/-1.4 (P<0.001) in the transplanted group, respectively, whereas the respective differences were not significant in the control group. The yearly progression rate of activity and fibrosis was significantly higher in the renal transplant group as compared with the immunocompetent group: 0.26+/-0.41 vs 0.01+/-0.19 (P<0.01) and 0.26+/-0.35 vs 0.05+/-0.21 (P<0.03), respectively. Twenty (71.5%) and 14 (50.0%) of the renal allograft recipients had activity and fibrosis progression as compared with four (16%) (P<0.001) and four (16%) (P<0.01) in immunocompetent patients; six kidney recipients (21.4%) evolved to cirrhosis vs only one in the control group (3.6%) (P=0.07). Liver-related mortality was significantly higher during the follow-up period in renal transplant patients than in the control group (10 vs 0%) (P<0.05). CONCLUSION: Using conventional immunosuppressive regimen, renal transplantation is associated with a more severe evolution of chronic hepatitis C as compared with HCV-infected immunocompetent subjects. Thus, the histopathological evaluation should be performed and anti viral therapy discussed before renal transplantation. PMID- 11773477 TI - A method to insert a haemodialysis catheter by parasternal access. PMID- 11773478 TI - Burkholderia pseudomallei infection, or melioidosis, and nephrotic syndrome. PMID- 11773479 TI - Development of IgA nephropathy 14 years after diagnosis of membranous nephropathy. PMID- 11773480 TI - Cyanotic congenital heart disease associated with glomerulomegaly and focal segmental glomerulosclerosis: remission of nephrotic syndrome with angiotensin converting enzyme inhibitor. PMID- 11773481 TI - Cidofovir-induced end-stage renal failure. PMID- 11773482 TI - Group A streptococcal bacteraemia and necrotizing faciitis in a renal transplant patient: a case for intravenous immunoglobulin therapy. PMID- 11773483 TI - Fibromuscular dysplasia in a living donor: early post-operative allograft artery stenosis with successful venous interposition. PMID- 11773485 TI - Stupor and flaccid paralysis in a patient with end-stage renal failure. PMID- 11773484 TI - Which type of dialysis in patients with cholesterol crystal embolism? PMID- 11773486 TI - Excessive fluid gain in a chronic laxative abuser: "pseudo-idiopathic" oedema. PMID- 11773487 TI - Progressive anorexia and chronic ascites after termination of CAPD. PMID- 11773488 TI - An eye for the diagnosis of chronic renal failure in young patients. PMID- 11773489 TI - Nail-patella syndrome--renal and musculo-skeletal features. PMID- 11773490 TI - Predilution haemofiltration. PMID- 11773491 TI - Focal glomerulosclerosis expanding from the glomerular vascular pole in a Japanese male with mitochondrial-DNA mutation. PMID- 11773492 TI - Lupus syndrome, hypothyroidism and bullous skin lesions after interferon alfa therapy for hepatitis C in a haemodialysis patient. PMID- 11773493 TI - Sarcoid presenting with hypercalcaemia and erythema nodosum in a haemodialysis patient. PMID- 11773494 TI - Does iron depletion induced by erythropoietin slow the progression of chronic kidney disease? PMID- 11773495 TI - Delayed life threatening complications after insertion of dialysis catheters. PMID- 11773500 TI - Hawthorn fruit is hypolipidemic in rabbits fed a high cholesterol diet. AB - The present study examined the hypolipidemic activity of hawthorn fruit. New Zealand white rabbits were fed one of three diets, a reference diet with no cholesterol added (NC), a high cholesterol diet (1 g/100 g, HC) and a HC diet supplemented with 2 g/100 g hawthorn fruit powder (HC-H). After 12 wk, serum total cholesterol (TC) and triacylglycerols (TG) were 23.4 and 22.2% lower, respectively, in the hawthorn fruit group compared with the HC rabbits (P < 0.05). Hawthorn supplementation led to 50.6% less cholesterol accumulation in aorta (P < 0.05) and 23-95% greater excretion of neutral and acidic sterols (P < 0.05). Supplementation of hawthorn fruit did not affect the activities of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA-R) or cholesterol 7alpha-hydroxylase (CH) but it suppressed the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT, P < 0.05). The results suggest that the mechanism by which hawthorn fruit decreases serum cholesterol involves, at least in part, the inhibition of cholesterol absorption mediated by down-regulation of intestinal ACAT activity. PMID- 11773501 TI - Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. AB - The aim of the present study was to determine whether dietary intake of monounsaturated (MUFA) and/or polyunsaturated fatty acids (PUFA) of the (n- 3) and (n-6) series could improve intestinal damage and reduce inflammation in experimental ulcerative colitis (UC). Rats were treated with 80 mg/kg body of 2,4,6-trinitrobenzenesulfonic acid and fed for 1 or 2 wk diets enriched in olive oil (OO), fish oil (FO), or purified pig brain phospholipids (BPL), as sources of monounsaturated and PUFA of the (n-3) and (n-3) + (n-6) series. Evaluation of macroscopic and microscopic colonic damage was assessed. Ultrastructural and histologic changes were analyzed as well as plasma and colonic mucosa fatty acid profiles and some biochemical markers of injury and inflammation [alkaline phosphatase (AP), mieloperoxidase (MPO), prostaglandin E(2) (PGE(2)) and leukotriene B(4)]. Fatty acid profiles of both plasma and mucosa mostly reflected the dietary fatty acid composition. Plasma MUFA proportions were higher in UC animals fed the OO diet compared with FO or BPL groups 1 and 2 wk and (n-3) long chain PUFA (LC-PUFA) were higher in the FO than in the OO and BPL groups. At 1 wk, UC led to lower MUFA mucosa levels and (n-3)LC-PUFA were higher in the FO group compared with the OO and BPL groups. Rats with UC fed FO at 1 wk showed significantly less macroscopic and microscopic colonic damage. They also have lower AP and MPO activities and PGE(2) levels compared with the OO and BPL groups and showed enhanced histological repair, less necrotic areas within the mucosa, and more goblet cells with mature mucin granules. These results suggest that the use of balanced diets containing (n-3) LC-PUFA could ameliorate the inflammation and mucosal damage in UC. PMID- 11773502 TI - Supplementation of the black rice outer layer fraction to rabbits decreases atherosclerotic plaque formation and increases antioxidant status. AB - The influence of the supplementation of black and white rice outer layer fractions on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in rabbits. Male rabbits (n = 32) were randomly divided into four groups. They were fed nonpurified diet (normal group), a lard (3.5 g/100 g) with high cholesterol (0.5 g/100 g) diet (HC group); the HC diet with 5 g/100 g white rice outer layer fraction (WRF group); or the HC diet with 5 g/100 g black rice outer layer fraction (BRF) for 2 mo. Blood samples were collected for determination of lipid concentration and oxidative and antioxidative status variables, and aortae were taken for the assessment of atherosclerotic plaques. The atherosclerotic plaque area in rabbits fed the BRF diet was 66% lower than that of the HC or WRF rabbits (P < 0.001). Supplementation of the black rice outer layer significantly (P < 0.05) lowered aortic 8-hydroxy-2'-deoxyguanosine (8-OHdG) (-52%, -44%) compared with the WRF or HC diets (P < 0.05). There were no differences in aortic 8-OHdG levels between rabbits fed the BRF and normal diets. The BRF diet significantly (P < 0.05) decreased the malondialdehyde (MDA) level of serum (-37%) and aortic artery (-50%) compared with the WRF diet. There were no differences in the concentrations of serum total cholesterol (TC), LDL cholesterol (LDL-C), HDL-C or the ratio of apoprotein (apo)I/apoB among the HC, WRF and BRF groups. Similarly, there were no differences in the serum vitamin E concentration and erythrocyte and aorta superoxide dismutase (SOD) activities among rabbits fed these diets. The serum concentration of most fatty acids except 18:1 did not differ between the WRF and the BRF groups. We conclude that the inhibition of atherosclerotic plaque formation derived from the black rice outer layer fraction in rabbits might be mediated by antioxidative or anti-inflammatory effects. PMID- 11773503 TI - Trifolium pratense (red clover) exhibits estrogenic effects in vivo in ovariectomized Sprague-Dawley rats. AB - Studies were conducted using an ovariectomized rat model to determine the estrogenic and antiestrogenic activity of Trifolium pratense L. (red clover) extracts. A red clover extract, standardized to contain 15% isoflavones was administered by gavage [250, 500 and 750 mg/(kg x d)] to virgin, ovariectomized 50-d-old Sprague-Dawley rats, for 21 d in the presence and absence of 17beta estradiol [50 microg/(kg x d)]. Estrogenic effects included an increase in uterine weight, vaginal cell cornification and mammary gland duct branching. Red clover produced a dose-dependent increase in uterine weight and differentiated vaginal cells at the two higher doses, but it did not stimulate cell proliferation in the mammary glands. Neither antiestrogenic nor additive estrogenic properties were observed in any of the tissues studied. These data suggest that red clover extract is weakly estrogenic in the ovariectomized rat model. PMID- 11773504 TI - Postprandial induction of chaperone gene expression is rapid in mice. AB - Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver. PMID- 11773505 TI - Characterization and regulation of a cloned ovine gastrointestinal peptide transporter (oPepT1) expressed in a mammalian cell line. AB - To investigate the kinetics of peptide transport by the peptide transporter, PepT1, Chinese hamster ovary cells were transfected with an expression vector containing our cloned ovine PepT1 cDNA. Transport was assessed by uptake studies using the radiolabeled dipeptide, [(3)H]-Gly-Sar. Expression of oPepT1 was detected at 8-24 h post-transfection with an optimal time of 16-24 h. Uptake of Gly-Sar by oPepT1 was pH-dependent with an optimal pH of 5.5-6.0, concentration dependent and saturable with an apparent K(m) value of 1.0 +/- 0.1 mmol/L and a maximum velocity of 14.3 +/- 0.4 nmol/(mg protein x 40 min). Competition studies with nonradiolabeled peptides and [(3)H]-Gly-Sar showed that all di- and tripeptides inhibited uptake of [(3)H]-Gly-Sar. In addition, three tetrapeptides (Met-Gly-Met-Met, Pro-Phe-Gly-Lys, and Val-Gly-Ser-Glu) also inhibited [(3)H]-Gly Sar uptake. There was no inhibition of [(3)H]-Gly-Sar uptake detected in the presence of nonradiolabeled free amino acids. Treatment of the cells with staurosporine, an inhibitor of protein kinase C (PKC) significantly increased the transport system. This increase was specific and could be blocked if treatment was done in the presence of phorbol 12-myristate-13-acetate (PMA), an activator of PKC. The staurosporine- and PMA-induced changes in peptide transport activity were not affected by cotreatment with cycloheximide. These data demonstrate that the transport of peptide substrates by oPepT1 in transfected mammalian cells is similar to that in microinjected Xenopus oocytes and that PKC phosphorylation plays a regulatory role in oPepT1 function. PMID- 11773506 TI - The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins. AB - The mechanisms by which dietary soy favorably influences lipoprotein metabolism and inhibits atherosclerosis are uncertain. Studies of blood mononuclear cells and cultured hepatocytes have indicated that certain soy peptides (i.e., 7S globulins) stimulate expression of LDL receptors. This pathway represents a hypothetical mechanism by which soy's hypocholesterolemic and antiatherosclerotic effects may be mediated. However, direct evidence supporting this hypothesis is lacking. To address this, we compared effects of dietary soy protein isolate in two genetically engineered mouse models of atherosclerosis. One mouse [LDL receptor -/- + apolipoprotein (apo) B transgenic] is devoid of LDL receptors and overproduces apolipoprotein B, whereas the other (apoE -/-) has a normal complement of LDL receptors but does not produce apolipoprotein E. Male (n = 10 12/group) and ovariectomized female (n = 10-12/group) mice were studied. There were three treatment groups, which differed principally by the source of the protein component of the diet: 1) casein/lactalbumin (no isoflavones), 2) alcohol washed soy protein isolate (total isoflavones = 0.04 mg/g), and 3) intact soy protein isolate (total isoflavones = 1.72 mg/g). Atherosclerosis was assessed by quantifying the aortic content of esterified cholesterol. Atherosclerosis was inhibited (relative to the casein/lactalbumin group) by both alcohol-washed (45 and 31%) (P < 0.05) and intact (65 and 41%) (P < 0.05) soy protein isolate in LDL receptor -/- and apoE -/- mice, respectively. There was no sex difference. In a two-way analysis, there were significant effects of type of soy isolate and type of mouse. The antiatherosclerosis effect was enhanced in LDL receptor -/- mice (P < 0.001) and diminished in mice fed alcohol-washed soy protein isolate (P < 0.001). Furthermore, inhibitory effects of soy on atherosclerosis were unrelated to plasma LDL, VLDL or HDL cholesterol concentrations. The results represent direct evidence for the existence of LDL receptor- and plasma lipoprotein independent pathways by which dietary soy protein isolate inhibits atherosclerosis. PMID- 11773507 TI - Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women. AB - Increased HDL-cholesterol levels have been associated with lower coronary heart disease (CHD) risk. However, HDL are heterogeneous lipoproteins, and particles enriched in apolipoprotein (Apo) AII have been associated with increased CHD risk. We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods, i.e., an oleic acid sunflower oil diet followed by a palmolein diet, each lasting 4 wk. The linoleic acid was kept at 4% total energy and the cholesterol intake at 400 mg/d. The palmolein diet increased serum total cholesterol (TC) (P < 0.001), phospholipids (P < 0.001), Apo AII (P < 0.001), HDL cholesterol (P < 0.05), HDL lipids (P < 0.05), HDL proteins (P < 0.01) and the HDL total mass (P < 0.05). The HDL cholesterol/Apo AI ratio was increased 22.0% (P < 0.05), whereas the HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4% (P < 0.01) and 30.4%, (P < 0.001), respectively. When the effects of the dietary intervention were examined according to the cholesterolemia status (< or >6.2 mmol/L), the most significant changes (P < 0.001) were related to Apo AII levels. Moreover, a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio. In summary, a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet; however, the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk. This effect was more marked in women with serum TC > 6.2 mmol/L. PMID- 11773508 TI - Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. AB - Prospective studies suggest that tea may protect against cardiovascular disease. A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea. Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation. Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2) isoprostane excretion. Study 1: The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a randomized 3-period (7 d each) crossover design. Study 2: The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a randomized 2 period (4 wk each) crossover design. F(2)-isoprostane excretion was not altered after regular ingestion of green tea (273 +/- 48 pmol/mmol creatinine) or black tea (274 +/- 39 pmol/mmol creatinine) in comparison with hot water (263 +/- 47 pmol/mmol creatinine; Study 1), or by regular ingestion of black tea (334 +/- 71 pmol/mmol creatinine) in comparison with hot water (355 +/- 75 pmol/mmol creatinine; Study 2). These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation. PMID- 11773509 TI - Somatotropin-induced amino acid conservation in pigs involves differential regulation of liver and gut urea cycle enzyme activity. AB - Somatotropin (ST) treatment promotes animal growth and allows for the conservation of amino acids by increasing nitrogen retention and reducing ureagenesis and amino acid oxidation. To determine whether the improvement in amino acid conservation with ST treatment involves regulation of urea cycle enzyme activities in both liver and intestine, growing swine were treated with either ST (150 microg x kg(-1) x d(-1)) or saline for 7 d. Fully fed pigs (n = 20) were infused intravenously for 2 h with NaH(13)CO(3) followed by a 4-h intraduodenal infusion of [1-(13)C]phenylalanine. Arterial and portal venous blood and breath samples were obtained at baseline and steady-state conditions for measurement of amino acid and blood urea nitrogen (BUN) concentrations and whole-body phenylalanine oxidation. Urea cycle enzyme activities were determined in liver and jejunum. ST decreased BUN (-46%), arterial (-34%) and portal venous (-43%) amino acid concentrations and whole-body phenylalanine oxidation (-30%). The activities of carbamoylphosphate synthase-I (-45%), argininosuccinate synthase (-38%), argininosuccinate lyase (-23%), arginase (-27%), and glutaminase (-18%), but not of ornithine carbamoyltransferase, ornithine aminotransferase, or glutamate dehydrogenase were reduced in liver of ST-treated pigs. ST slightly increased intestinal activity of glutaminase (+9%) but did not affect that of any other enzymes. ST decreased hepatic, but increased jejunal, N-acetylglutamate (an essential allosteric activator of carbamoylphosphate synthase-I; -26% and +32%, respectively) and carbamoylphosphate (a substrate for ornithine carbamoyltransferase; -20% and +28%, respectively) content. These results demonstrate that the reduced amino acid catabolism with ST treatment in growing pigs involves a reduction in hepatic urea cycle enzyme activities. The effect of ST treatment on porcine urea cycle enzymes is tissue-specific and is associated with a reduction in substrate availability for hepatic ureagenesis. PMID- 11773510 TI - Choline deficiency-induced liver damage is reversible in Pemt(-/-) mice. AB - Hepatic tissue has two pathways for phosphatidylcholine (PC) synthesis, i.e., the cytidinediphosphocholine (CDP-choline) pathway and the methylation pathway, which utilizes phosphatidylethanolamine-N-methyltransferase (PEMT). Fatal liver damage occurs in Pemt(-/-)mice fed a choline-deficient (CD) diet. We investigated whether liver damage can be reversed by the addition of dietary choline. Mice (8 wk old) were fed the CD purified diet for 4 d, a choline-supplemented (CS) diet (CD diet + 0.4% choline chloride) for 4 d, or the CD diet for 3 d and a CS diet for 1 d (CD/CS). Pemt(-/-)mice fed the CD diet for 3 d exhibited liver damage as assayed by plasma aminotransferase levels. The livers appeared normal after subsequent feeding of the CS diet for 1 d (CD/CS). The activities of plasma aminotransferases of CD/CS fed mice were comparable to Pemt(-/-)mice fed the CS diet. Hepatic PC and triacylglycerol levels as well as plasma PC levels in the CD/CS-fed Pemt(-/-)mice were lower than those of mice fed the CD diet and began to approach normal levels. Although the CD diet induces liver damage in Pemt(-/ )mice, this damage can be rapidly reversed by the addition of dietary choline. PMID- 11773511 TI - Docosahexaenoic acid is superior to eicosapentaenoic acid as the essential fatty acid for growth of grouper, Epinephelus malabaricus. AB - Juvenile grouper (Epinephelus malabaricus) were fed seven experimental diets, one control diet and one reference diet for 12 wk to determine the dietary requirement of grouper for docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Each of the seven diets contained 1 g/100 g DHA and EPA in various combinations and 9 g/100 g tristearin. The control diet contained 1 g/100 g trilinolenin and trilinolein (3:1, wt/wt), and no supplemental EPA or DHA. The reference diet contained only natural oils from a mixture of cod liver oil, linseed oil and safflower oil at a ratio of 2:1:1 (wt/wt/wt). Significant differences (P < 0.05) in growth were observed among the dietary treatments but not in survival rate or relative liver weight. Only the diet with the highest DHA/EPA ratio (3:1) promoted significantly greater growth than the control diet. Purified EPA and DHA did not perform better in promoting growth than did the impure EPA and DHA oils. Enhanced growth was observed when the dietary DHA/EPA ratio was greater than 1, indicating that DHA was superior to EPA in promoting fish growth. Neutral lipid (NL) was the predominant lipid fraction (>70%) in both liver and muscle. Tissue NL/polar lipid did not differ among groups except the reference diet group that had a higher ratio (P < 0.05). DHA and EPA levels in the grouper tissues, especially muscle, were highly reflective of dietary levels of DHA and EPA, indicating that direct incorporation was likely. In addition, the 20:1(n-9), concentration in NL fractions seems to be an appropriate indicator of dietary essential fatty acid deficiency in grouper. PMID- 11773512 TI - Nondigestible oligosaccharides do not increase accumulation of lipid soluble environmental contaminants by mice. AB - Supplementing diets with nondigestible fibers that are fermented by the gastrointestinal tract bacteria increases the dimension and absorptive capacities of the small intestine; we hypothesized that this would increase the accumulation of environmental contaminants. This was tested by feeding mice for 6-8 wk diets with fiber at two levels (0 and 100 g/kg) and from different sources (cellulose, lactosucrose, polydextrose, indigestible dextrin, inulin) before a 2-wk oral exposure to (14)C-labeled mirex or methylmercury in combination with (3)H-labeled retinol. Concentrations of contaminants and retinol were measured in urine and feces collected for the last 2 d of exposure and in seven tissues (small and large intestine, brain, liver, kidneys, gastrointestinal tract mesentery, gall bladder). Mice fed the same diets, but not exposed to the contaminants, were used for routine microbiology of alimentary canal contents, measurements of intestinal dimensions and in vitro rates of glucose, mirex, methylmercury and retinol absorption by the small intestine. Mice fed the diets with nondigestible oligosaccharides had higher densities of anaerobic bacteria and larger small and large intestines, but did not have greater rates of contaminant absorption or accumulation. Mice exposed to methylmercury accumulated less retinol than mice exposed to mirex. Although diets with nondigestible oligosaccharides fibers reduce accumulation of environmental contaminants, but not retinol, the specific responses vary among tissues, sources of fiber and contaminants. The mechanisms responsible for the influence of nondigestible oligosaccharides can include reduced absorption, increased fecal elimination and transformation to forms that are excreted in the urine. PMID- 11773513 TI - Total fat and (n-3):(n-6) fat ratios influence eicosanoid production in mice. AB - Previous studies have not addressed the effect of differing fat intake on the effectiveness of varying (n-3) polyunsaturated fatty acid (PUFA) ingestion in altering tissue composition and eicosanoid production. This study examined (n 3):(n-6) PUFA ratios of 0, 0.1:1, 0.2:1, 0.4:1, and 1:1 with total fat at 5, 10, 15, and 20 g/100 g of diet and (n-6) PUFA fixed at 1.5 g/100 g of diet on tissue composition and peritoneal cell eicosanoid response to an in vivo inflammatory stimulus in 240 mice. Both (n-3) PUFA and total fat intake influenced tissue composition and eicosanoid biosynthesis. Increased (n-3) PUFA intake was associated with an increase in tissue (n-3) PUFA and a decrease in long-chain (n 6) PUFA. Although hepatic tissue linoleic acid (LA) was not altered by (n-3) PUFA intake or changes in total fat, peritoneal cell LA increased in response to increasing total fat but was unaffected by changes in dietary (n-3) PUFA. Four series leukotrienes (LT) decreased progressively with increased (n-3) PUFA at all fat intake levels. In addition, four-series LT decreased with increased total fat at low (n-3):(n-6) ratios (0 and 0.1). At high (n-3):(n-6) ratios (0.4 and 1.0) increasing dietary fat between the 5 and 15 g/100 g diets increased four-series LT synthesis, which reached a plateau between 15 and 20 g fat/100 g diets. Five series LT production generally rose with increased (n-3) PUFA intake; this effect was most evident in mice fed the 5 g fat/100 g diet. Increasing total dietary fat at the three highest (n-3):(n-6) ratios (0.2, 0.4, 1.0) decreased five-series LT production. Elevated (n-3) PUFA and total fat intake exerted an additive effect with respect to prostacyclin (PGI(2)) production because it was reduced with increasing intakes of both. Compared with the mice consuming the no (n-3) 5 g/100 g diets, PGI(2) levels were reduced by 88% in mice consuming the highest total fat and (n-3) PUFA diets. At low fat intake (5 and 10 g/100 g diet), increasing the (n-3) PUFA intake was associated with a decrease in PGE(2) synthesis. However, unlike PGI(2), high fat intake reduced PGE(2) to basal levels with no further reduction induced by increased (n-3) PUFA intake. PMID- 11773514 TI - Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal. AB - Aging is characterized by a progressive loss of muscle mass. A decrease of muscle protein synthesis stimulation has been detected in the postprandial state and correlated to a decrease of muscle protein synthesis sensitivity to leucine in vitro. This study was undertaken to examine the effect of a leucine-supplemented meal on postprandial (PP) muscle protein synthesis during aging. Adult (8 mo old) and old (22 mo old) rats were fed a semiliquid 18.2% protein control diet for 1 mo. The day of the experiment, rats received no food (postabsorptive group) or either an alanine or leucine-supplemented meal for 1 h (postprandial groups: PP and PP + Leu groups, respectively). Muscle protein synthesis was assessed in vivo 90-120 min after the meal distribution using the flooding dose method (1-(13)C phenylalanine). Plasma leucine concentrations were significantly greater in the PP + Leu group compared with the PP group at both ages. Muscle protein synthesis was significantly greater in the adult PP group, whereas it was not stimulated in the old PP group. When supplemented with leucine, muscle protein synthesis in old rats was stimulated and similar to that observed in adults. We conclude that acute meal supplementation with leucine is sufficient to restore postprandial stimulation of muscle protein synthesis in old rats. Whether chronic leucine meal supplementation may limit muscle protein wasting during aging remains to be verified. PMID- 11773515 TI - Effect of the AIN-93M purified diet and dietary restriction on survival in Sprague-Dawley rats: implications for chronic studies. AB - Survival, growth and dietary intake (DI) variables were monitored in a chronic 114-wk study in which male Sprague-Dawley rats [n = 120; National Center for Toxicological Research (NCTR) colony] consumed the AIN-93M purified diet ad libitum (AL), or an amount reduced by 31% of total AL intake inclusive of all macro- and micronutrients. The main objectives were to ascertain the survival characteristics of rats fed the AIN-93M diet and to determine whether dietary restriction (DR) increases longevity of rats fed this casein-based diet compared with the use of mixed-protein sources of the NIH-31 cereal-based diet in an earlier study. Body, liver, brain, the brain/body ratio, spleen, thymus and kidney weights, body length and body density were decreased (P < 0.05) by DR, whereas testis weight and skull length were not altered by DR. Significant age effects at 58 and 114 wk were found for body, brain, the brain/body ratio, liver and testis weights, and body density. Survival rates for the AL and 31% DR groups were 43.3 and 57.5%, respectively. Survival curves were not significantly different. The survival rate for AL rats fed the AIN-93M diet was not different from that of AL rats fed the NIH-31 diet (43.3 and 51.7%, respectively). However, the survival rate for 31% DR rats fed the AIN-93M diet was significantly lower than 25% DR rats fed the NIH-31 diet (57.5 and 87.5%, respectively) although both groups had similar body weights and energy intake at various ages. Nutritional components in the NIH-31 diet that are missing and/or reduced in the AIN-93M diet may interact with DR to increase 114-wk survival. Although the survivability, growth and anatomical results of this study suggest that the AIN-93M diet is suitable for chronic rodent studies, additional studies such as comprehensive histopathologic and physiologic investigations must be undertaken to complete the evaluation process. PMID- 11773516 TI - Niacin deficiency decreases bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. AB - Cancer chemotherapy agents cause damage in the bone marrow, resulting in leukopenia during treatment and secondary cancers after recovery from the original disease. We created an experimental model of alkylation-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin status on cancer induction. For 4 wk, nontumor-bearing weanling Long-Evans rats were fed niacin-deficient (ND) diets or were pair-fed (PF) identical quantities of a niacin-adequate diet. One week after the initiation of niacin feeding protocols, ENU treatment began (12 doses, 30 mg/kg by gavage, every other day). At the end of dietary modulation and ENU treatment, all rats were fed a high quality control diet and monitored for weight loss (>5%) and palpable tumors (>1cm), at which point they were necropsied for the presence of disease. The morbidity curves were significantly different; ND rats reached 20% morbidity 10 wk earlier than PF rats. In the first 20 wk after ENU treatment, ND rats developed 17 malignancies, including 11 leukemias, whereas PF rats developed 3 malignancies with 2 leukemias. In the end, there was a 47% greater average number of malignancies in ND vs. PF rats, despite a more rapid onset of morbidity. In short-term studies, niacin deficiency caused an 80% decrease in bone marrow NAD(+). Basal poly(ADP-ribose) levels were dramatically reduced by niacin deficiency. A single dose of ENU increased poly(ADP-ribose) levels fivefold in PF rats, whereas levels in ND rats remained 90% lower. Niacin deficiency did not alter the initial accumulation of DNA damage, indicating that drug metabolism is not an underlying factor in the diet-induced changes. These data show that niacin deficiency alters poly(ADP-ribose) metabolism in the bone marrow and increases the risk of nitrosourea-induced leukemias. PMID- 11773517 TI - Pharmacological intakes of niacin increase bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. AB - Cancer chemotherapy agents cause short-term leukopenia during treatment and the development of secondary leukemias after recovery from the original disease. We reported that niacin deficiency in rats increases the severity of nitrosourea induced leukopenia and the subsequent development of cancers. This study was designed to test the effects of supplementing an already high quality diet with pharmacologic levels of niacin. For a period of 4 wk, nontumor-bearing weanling Long-Evans rats were pair-fed AIN-93M diets that were niacin adequate (30 mg/kg diet) or pharmacologically supplemented (4 g/kg diet) with nicotinic acid (NA) or nicotinamide (Nam). One week after the initiation of niacin feeding protocols, ethylnitrosourea (ENU) treatment began (12 doses, 30 mg/kg by gavage, every other day). ENU treatment caused leukopenia, which was not prevented by niacin supplementation. At the end of ENU treatment, all rats were switched to a niacin adequate diet and monitored. Within 36 wk after the start of treatment, all of the ENU-treated rats either lost 5% of peak body weight or had palpable tumors > 1 cm in diameter, and were necropsied. Supplementation with NA or Nam at 4.0 g/kg diet (combined analysis) increased the latency of the ENU-induced morbidity curve, relative to niacin-adequate controls. Morbidity could be attributed in almost all cases to some form of neoplasm, with leukemias the predominant form. In short-term studies, supplementation with either NA or Nam caused dramatic increases in bone marrow NAD(+) (1- to 1.5-fold), basal poly(ADP-ribose) (3- to 5 fold) and ENU-induced poly(ADP-ribose) levels (1.5-fold). These data show that supplementation of a niacin-adequate, high quality diet with pharmacologic levels of nicotinic acid or nicotinamide increases NAD(+) and poly(ADP-ribose) levels in bone marrow and may be protective against DNA damage. PMID- 11773518 TI - Beta-carotene alters the morphology of NCI-H69 small cell lung cancer cells. AB - The effect of beta-carotene on the morphology of NCI-H69 small cell lung cancer cells that had undergone beta-carotene-induced growth reduction (P < 0.05) was examined. The cells were grown at 1 x 10(8) cells/L and were cultured with or without 20 micromol/L beta-carotene. The qualitative electron microscopic observations revealed that beta-carotene-treated cells contained more vacuoles than control cells not treated with beta-carotene. The quantitative image analysis showed a significantly smaller (P < 0.05) value of the nuclear roundness factor for treated cells compared with control cells, indicating an irregular nuclear morphology of beta-carotene-treated cells. The major diameter of the cells and the minor diameter of the nuclei were significantly smaller (P < 0.05), and the nuclear perimeter was significantly larger (P < 0.05) in beta-carotene treated cells. The ratio of nucleus to cytoplasm was significantly less (P < 0.05) in beta-carotene-treated cells compared with control cells, indicating a less malignant growth of the cells. These results demonstrate that the treatment of small cell lung cancer cells with beta-carotene induces morphological changes in the cells concomitant with a reduction in their proliferation. Further investigation is required to show a direct effect of beta-carotene or its intracellular polar metabolites on the morphology of these cells. PMID- 11773519 TI - Peripheral and splanchnic metabolism of dietary nitrogen are differently affected by the protein source in humans as assessed by compartmental modeling. AB - We used a previously developed compartmental model to assess the postprandial distribution and metabolism of dietary nitrogen (N) in the splanchnic and peripheral areas after the ingestion of a single mixed meal containing either (15)N-labeled milk or soy purified protein. Although the lower whole-body retention of dietary N from soy protein was measured experimentally, the splanchnic retention of dietary N was predicted by the model not to be affected by the protein source, and its incorporation into splanchnic proteins was predicted to reach approximately 35% of ingested N at 8 h after both meals. However, dietary N intestinal absorption and its appearance in splanchnic free amino acids were predicted to be more rapid from soy protein and were associated with a higher deamination, concomitant with a higher efficiency of incorporation of dietary N into proteins in the splanchnic bed. In contrast, soy protein was predicted to cause a reduction in peripheral dietary N uptake, as a consequence of both similar splanchnic retention and increased oxidation compared with milk protein. In addition, protein synthesis efficiency was reduced in the peripheral area after soy protein intake, leading to dietary N incorporation in peripheral proteins that fell from 26 to 19% of ingested N 8 h after milk and soy protein ingestion, respectively. Such a model thus enables a description of the processes involved in the differential metabolic utilization of dietary proteins and constitutes a valuable tool for further definition of the notion of protein quality during the period of protein gain. PMID- 11773520 TI - The key to an enigma: how do dietary polyunsaturated fatty acids lower serum cholesterol? PMID- 11773521 TI - Thioredoxin-mediated reductive activation of a protein kinase for the regulatory phosphorylation of C4-form phosphoenolpyruvate carboxylase from maize. AB - The activity of phosphoenolpyruvate carboxylase (PEPC, EC4.1.1.31) for the C4 photosynthesis is known to be regulated mainly in response to light/dark transitions through reversible phosphorylation by a specific protein kinase (PK). PEPC-PK with an M(r) of 30 kDa was purified about 1.4 million-fold to homogeneity from maize leaves and characterized. The purified PEPC-PK was readily inactivated under mild oxidative conditions, but the activity could be recovered by dithiothreitol (DTT). The recovery by DTT was strongly accelerated by thioredoxin (Trx) from E. coli. Trxs of plant origin such as Trx-m from spinach chloroplast and Trx-h from rice cytoplasm were also effective. These results suggest the possibility of PEPC-PK being redox-regulated via Trx in vivo. PMID- 11773522 TI - Separate localization of light signal perception for sun or shade type chloroplast and palisade tissue differentiation in Chenopodium album. AB - Physiological and ecological characteristics of sun and shade leaves have been compared in detail, but their developmental processes, in particular their light sensory mechanisms, are still unknown. This study compares the development of sun and shade leaves of Chenopodium album L., paying special attention to the light sensory site. We hypothesized that mature leaves sense the light environment, and that this information determines anatomy of new leaves. To examine this hypothesis, we shaded plants partially. In the low-light apex treatment (LA), the shoot apex with developing leaves was covered by a cap made of a shading screen and received photosynthetically active photon flux density (PPFD) of 60 micromol m(-2 )s(-1), while the remaining mature leaves were exposed to 360 micromol m(-2 )s(-1). In the high-light apex treatment (HA), the apex was exposed while the mature leaves were covered by a shade screen. After these treatments for 6 d, we analyzed leaf anatomy and chloroplast ultrastructure. The anatomy of LA leaves with a two-layered palisade tissue was similar to that of sun leaves, while their chloroplasts were shade-type with thick grana. The anatomy of HA leaves and shade leaves was similar and both had one-layered palisade tissue, while chloroplasts of HA leaves were sun-type having thin grana. These results clearly demonstrate that new leaves differentiate depending on the light environment of mature leaves, while chloroplasts differentiate depending on the local light environment. PMID- 11773523 TI - Reappraisal of the currently prevailing model of starch biosynthesis in photosynthetic tissues: a proposal involving the cytosolic production of ADP glucose by sucrose synthase and occurrence of cyclic turnover of starch in the chloroplast. AB - A vast amount of information has accumulated which supports the view that sucrose and starch are end-products of two segregated, yet highly interconnected, gluconeogenic pathways taking place in the cytosol and chloroplast, respectively. However, several lines of experimental evidences indicate that, essentially identical to the case of heterotrophic tissues, starch formation in the photosynthetic tissues may involve the direct import to the chloroplast of cytosolic hexose (C6) units derived from the sucrose breakdown. This evidence is consistent with the idea that synthesis of a sizable pool of ADP-glucose takes place in the cytosol by means of sucrose synthase whereas, basically in agreement with recent investigations dealing with glycogen biosynthesis in bacteria and animals, chloroplastic phosphoglucomutase and ADP-glucose pyrophosphorylase are most likely playing a role in channelling of glucose units derived from the starch breakdown in the chloroplast, thus making up a regulatory starch turnover cycle. According to this new view, we propose that starch production in the chloroplast is the result of a flexible and dynamic mechanism wherein both catabolic and anabolic reactions take place simultaneously in a highly interactive manner. Starch is seen as an intermediate component of a cyclic gluconeogenic pathway which, in turn, is connected with other metabolic pathways. The possible importance of metabolic turnover as a way to control starch production is exemplified with the recently discovered ADP-glucose pyrophosphatase, an enzyme likely having a dual role in controlling levels of ADP glucose linked to starch biosynthesis and diverting carbon flow towards other metabolic pathways. PMID- 11773524 TI - A pathogen-induced chitin-binding protein gene from pepper: its isolation and differential expression in pepper tissues treated with pathogens, ethephon, methyl jasmonate or wounding. AB - A chitin-binding protein (CBP) cDNA (CACBP1) was isolated from a cDNA library of pepper (Capsicum annuum L.) leaves infected with Xanthomonas campestris pv. vesicatoria. The deduced amino acid sequence of the CACBP1 gene which has chitin binding domain and hinge region shares a high level of identity with CBP sequences from tomato, potato and tobacco. The CACBP1 gene was organ-specifically regulated in pepper plants, and differentially induced during the compatible and incompatible interactions of pepper with X. campestris pv. vesicatoria or Phytophthora capsici. Expression of the CACBP1 gene was rapidly induced in the incompatible interactions upon pathogen infection. Transcripts of the CACBP1 gene was highly inducible in the leaves of matured pepper plants by Colletotrichum coccodes infection. In situ hybridization results showed that CACBP1 mRNA was expressed in the phloem area of vascular bundles in C. coccodes-infected leaf tissues. The pathogen-inducible CACBP1 gene was also strongly induced and accumulated in pepper leaves by ethephon, methyl jasmonate or wounding. These data suggest that ethylene and jasmonate may act as signal molecules in the signal transduction pathways of the CBP gene induction during the pepper defense- or pathogenesis-related plant responses. PMID- 11773525 TI - Identification of functional domains of the extrinsic 12 kDa protein in red algal PSII by limited rroteolysis and directed mutagenesis. AB - The extrinsic 12 kDa protein in red algal photosystem II (PSII) functions to minimize the chloride and calcium requirement of oxygen-evolving activity [Enami et al. (1998) Biochemistry 37: 2787]. In order to identify functional domains of the 12 kDa protein, we prepared the 12 kDa protein lacking N-terminal peptides or C-terminal peptides or both by limited proteolysis and directed mutagenesis. The resulting 12 kDa protein fragments were examined for their binding and functional properties by reconstitution experiments. (1) A peptide fragment from Gly-6 to C terminus of the 12 kDa protein was prepared by V8 protease. This fragment rebound to PSII completely, and it reactivated oxygen evolution partially in the absence of Cl(-) and Ca(2+) ions but significantly in the presence of Cl(-) ion. (2) A peptide from Leu-10 to Phe-83 was obtained by chymotrypsin treatment. This peptide rebound to PSII effectively, but the rebinding did not restore oxygen evolution in both the absence and presence of Cl(-) and Ca(2+) ions. (3) Two mutant proteins, one lacking five residues and the other lacking nine residues of the N-terminus, were able to bind to PSII effectively. Recovery of oxygen evolution by their binding was almost the same as that reconstituted with the V8 protease-treated peptide. (4) Three mutant proteins lacking ten, seven or three residues of the C-terminus effectively rebound to PSII, but their binding did not result in recovery of the oxygen evolution. In contrast, reconstitution with a mutant protein lacking one residue of the C-terminus showed the same high restoration of oxygen evolution as reconstitution with the full-length 12 kDa protein. (5) These results indicate that two residues from lysine of the C terminus of the 12 kDa protein constitute an important domain for minimizing the chloride and calcium requirement of oxygen evolution. In addition, the N-terminus of the protein, at least five residues, has a secondary function for the chloride requirement. PMID- 11773526 TI - Differential expression of two cytochrome P450s involved in the biosynthesis of flavones and anthocyanins in chemo-varietal forms of Perilla frutescens. AB - In Perilla frutescens, there are two varietal forms of anthocyanin accumulation, i.e. red and green forms. The cDNA clones encoding flavone synthase II (FSII) and flavonoid 3'-hydroxylase (F3'H), two cytochrome P450s that are involved in the biosynthesis of flavones and anthocyanins, were isolated from P. frutescens. The FSII cDNA encoded a 57.1 kDa protein designated as CYP93B6, and the F3'H cDNA encoded 57.5 kDa protein designated as CYP75B4. Recombinant CYP93B6 expressed in yeast converted flavanones to flavones with K(m) values of 8.8-11.9 microM. Recombinant CYP75B4 catalyzed 3'-hydroxylation of flavanones to the corresponding compounds with K(m) values of 18-20 microM. The CYP93B6 transcript accumulated to an equal level in leaves of both red and green forms of P. frutescens, in agreement with the accumulation pattern of flavones in the leaves. However, the CYP75B4 transcript was predominantly expressed in the red form of P. frutescens, and its expression was induced by light in conjunction with other transcripts of biosynthetic enzymes of anthocyanin. These results indicate that gene expression of a set of anthocyanin biosynthetic enzymes including F3'H is regulated coordinately only in the red form of P. frutescens but not in the green form, whilst FSII gene expression is controlled in a similar manner in red and green forms of P. frutescens. PMID- 11773527 TI - OARE-1, a Ty1-copia retrotransposon in oat activated by abiotic and biotic stresses. AB - Transcriptionally active Ty1-copia LTR-retrotransposons were found in oat using RT-PCR for amplifying the reverse transcriptase domain. Sequence analysis of the RT-PCR clones suggested that oat LTR-retrotransposons consist of at least seven groups, which were tentatively designated as Oatrt1 to Oatrt7. A full length copy of Oatrt1 was isolated from an oat genomic library, and was designated OARE-1. OARE-1 was 8,665 bp long and a member of the BARE-1 subgroup. The oat genome carried it in multiple copies (at least 10,000 copies / a hexaploid genome). The expression of OARE-1 was intensively induced by wounding, UV light, jasmonic acid and salicylic acid, and its pattern was very similar to that of the PAL (phenylalanin ammonia lyase) gene. Furthermore, OARE-1 was highly activated by infection with an incompatible race of the crown rust fungus, Puccinia coronata. These results suggest that OARE-1 is highly sensitive to various abiotic and biotic stimuli leading to plant defense responses. PMID- 11773528 TI - Absence of carotenes and presence of a tertiary methoxy group in a carotenoid from a thermophilic filamentous photosynthetic bacterium Roseiflexus castenholzii. AB - We identified pigments in a thermophilic filamentous photosynthetic bacterium Roseiflexus castenholzii strain HL08. We detected neither bacteriochlorophyll (BChl) c nor carotenes in this bacterium cultured under the aerobic dark and the anaerobic light conditions, which may correspond to its lack of chlorosomes. In the cells cultured under the aerobic dark conditions, the carotenoids were derivatives of keto-gamma-carotene, and the major ones were methoxy-keto myxocoxanthin and keto-myxocoxanthin glucoside fatty acid ester. Although the tertiary methoxy group at C-1' and the double bond at C-3',4' in the psi end group of carotenoid, such as spirilloxanthin, have only been found in purple bacteria, this was the first such report in other bacterial groups. The fatty acid moiety was composed of iso fatty acids, which were rare in the cellular lipids. In the cells cultured under the anaerobic light conditions, in addition to these keto-carotenoids, we also found non-oxidized carotenoids (derivatives of gamma-carotene). Concerning the esterifying alcohol of BChl a, we found a substantial amount of geranylgeraniol, although the major component was phytol. The existence of these pigments makes this bacterium unique among the known species in CHLOROFLEXACEAE. PMID- 11773529 TI - Blue-light-dependent osmoregulation in protoplasts of Phaseolus vulgaris Pulvini. AB - Blue light was found to induce shrinkage of the protoplasts isolated from first leaf lamina pulvini of 18-day-old Phaseolus vulgaris. The response was transient following pulse stimulation, while it was sustainable during continuous stimulation. No apparent difference was found between flexor and extensor protoplasts. Protoplasts of the petiolar segment located close to the pulvinus showed no detectable response. In the plants used, the pulvinus was fully matured and the petiole was ceasing its elongation growth. When younger, 12-day-old, plants were used, however, the petiolar protoplasts did respond to blue light. The pulse-induced response was similar to that in pulvinar protoplasts, although the response to continuous stimulation was transient and differed from that in pulvinar protoplasts. No shrinkage was induced in pulvinar protoplasts when the far-red-light-absorbing form of phytochrome was absent for a period before blue light stimulation, indicating that the blue-light responsiveness is strictly controlled by phytochrome. Inhibitors of anion channels and H(+)-ATPase abolished the shrinking response, supporting the view that protoplasts shrink by extruding ions. The response of pulvinar protoplasts is probably involved in the blue-light induced, turgor-based movement of pulvini. The blue-light responding system in pulvini is suggested to have evolved from that functioning in other growing organs. PMID- 11773530 TI - Alternative oxidase in durum wheat mitochondria. Activation by pyruvate, hydroxypyruvate and glyoxylate and physiological role. AB - In order to gain a first insight into the alternative oxidase (AO) function in durum wheat mitochondria (DWM), we investigated some activation pathways of this enzyme in DWM purified from both etiolated shoots and green leaves. AO was activated when DWM were added with either pyruvate, known as an AO activator in other plant mitochondria, or alanine plus 2-oxoglutarate, which can generate intramitochondrial pyruvate and glutamate via transamination. In contrast, no AO activity was observed during oxidation of malate plus glutamate or succinate (which can generate malate). In this regard DWM differ from other plant mitochondria. Moreover, DWM were found: (i) to have a very low malic enzyme (ME) activity, (ii) to release oxaloacetate rather than pyruvate during malate oxidation and (iii) to poorly oxidise malate in the absence of glutamate, which removes oxaloacetate via transamination. Therefore, we show that, unlike other plant mitochondria, no pyruvate is generated inside DWM from malate via ME, allowing no AO activity. Other AO activators, alternative to pyruvate, were checked by evaluating the capability of several compounds to induce oxygen uptake and/or electrical membrane potential (Delta Psi) in cyanide-treated DWM. Hydroxypyruvate and glyoxylate, photorespiratory cycle intermediates, were found to be powerful AO activators, capable of inducing a maximal rate of cyanide insensitive oxygen uptake 1.7 times and 2.3 times higher than pyruvate, respectively. These results suggest that in durum wheat a link may exist between AO activity and photorespiratory metabolism rather than malate metabolism. Moreover, we observed that AO activation resulted in both a partially coupled respiration and a reduction by half of the rate of superoxide anion generation; therefore, AO is expected to work as an antioxidative defence system when the photorespiratory cycle is highly active, as under environmental stress. PMID- 11773531 TI - Involvement of superoxide generation in salicylic acid-induced stomatal closure in Vicia faba. AB - Salicylic acid (SA), the known mediator of systemic acquired resistance, induced stomatal closure of Vicia faba L. Application of SA to the epidermal peels evoked an elevation of chemiluminescence of Cripridina lucigenin-derived chemiluminescent reagent (CLA) which is sensitive to superoxide anion (O(2)(.-)). The SA-induced generation of chemiluminescence was suppressed by O(2)(.-) specific scavengers superoxide dismutase (SOD) and 4,5-dihydroxy-1,3 benzenedisulfonic acid (Tiron). These results suggest that O(2)(.-) was generated in epidermal peels by SA-treatment. A peroxidase inhibitor salicylhydroxamic acid (SHAM) inhibited guaiacol peroxidase activity and suppressed the SA-induced CLA chemiluminescence in the epidermal peels, suggesting that O(2)(.-) generation occurred by the peroxidase-catalyzed reaction as proposed for SA-treated tobacco cell suspension culture [Kawano et al. (1998) Plant Cell Physiol. 39: 721]. SOD, Tiron or SHAM suppressed the SA-induced stomatal closure. Moreover, application of superoxide-generating system also induced stomatal closure. These results support the concept of involvement of reactive oxygen species in signal transduction in SA-induced stomatal closure. PMID- 11773532 TI - Photosystem II damage and repair cycle in the green alga Dunaliella salina: involvement of a chloroplast-localized HSP70. AB - The involvement of HSP70B in the photosystem II damage and repair process in Dunaliella salina was investigated. A full-length cDNA of the D. salina hsp70B gene was cloned and sequenced. Expression patterns of the hsp70B gene were investigated upon shifting a D. salina culture from low-light to high-light growth conditions, designed to significantly accelerate the rate of PSII photodamage. Northern blot analyses and nuclear run-on transcription assays revealed a significant but transient induction of hsp70B gene transcription, followed by a subsequent increase in HSP70B protein synthesis and accumulation. Mild detergent solubilization of photoinhibited thylakoid membranes, in which photodamaged PSII centers had accumulated, followed by native gel electrophoresis revealed the formation of a 320 kDa protein complex that contained, in addition to the HSP70B, the photodamaged but as yet undegraded D1 protein as well as D2 and CP47. Evidence suggested that the 320 kDa complex is a transiently forming PSII repair intermediate. Denaturing solubilization of the 320 kDa PSII repair intermediate by SDS-urea resulted in cross-linking of its polypeptide constituents, yielding a 160 kDa protein complex. The role of the HSP70B in the repair of photodamaged PSII centers, e.g. in stabilizing the disassembled PSII core complex and in facilitating the D1 degradation and replacement process, is discussed. PMID- 11773533 TI - Identification of a gene required for cis-to-trans carotene isomerization in carotenogenesis of the cyanobacterium Synechocystis sp. PCC 6803. AB - A disruptive mutant of the sll0033 gene of the cyanobacterium Synechocystis sp. PCC 6803 produced primarily cis carotenes and small amounts of all-trans carotenes, but no xanthophylls, under dark conditions. Under light conditions, however, it produced normal carotenoids, that were the same as those produced by wild-type cells grown under both light and dark conditions. When the mutant cells cultured under dark conditions were irradiated, cis-isomers of carotenes were converted to all-trans lycopene. These findings demonstrate that this gene, designated crtH, is involved in the isomerization of cis-carotenes to all-trans forms in dark conditions, and that cis-carotenes were also converted to all-trans forms under light conditions by photoisomerization. PMID- 11773534 TI - Infant heart transplantation at Stanford: growth and neurodevelopmental outcome. AB - OBJECTIVE: To evaluate the growth and neurodevelopmental outcome of 18 surviving Stanford patients who received heart transplantations before their second birthday. METHODS: We compared the growth and neurodevelopmental outcome of these 18 patients with a second group of age-matched comparison patients who underwent other heart surgery requiring cardiopulmonary bypass. RESULTS: Difficulties with growth and development were more common in the transplant group as were neurologic abnormalities. Speech and language delays as well as hearing problems were also more common in the transplant group. CONCLUSION: Multicenter prospective longitudinal neurodevelopmental outcome studies of infant heart transplant patients should be conducted to provide a more efficient basis for evaluating management protocols and assessment of long-term outcomes and of the need for early intervention services. PMID- 11773535 TI - Gastroesophageal reflux and apnea of prematurity: no temporal relationship. AB - OBJECTIVE: A relationship between gastroesophageal reflux (GER) and apnea of prematurity (AOP) has long been suspected but is difficult to prove because most GER in this age group is nonacidic and thus undetectable by pH monitoring, the current standard for GER detection. The new multiple intraluminal impedance (MII) technique allows pH-independent reflux detection via changes in impedance caused by a liquid bolus inside the esophagus. We used this technique to investigate whether there is a temporal relationship between GER and AOP and whether GER occurs predominantly before a cardiorespiratory (CR) event. METHODS: Nineteen infants with AOP (median gestational age at birth: 30 weeks; range: 24-34; age at study: 26 days [13-93]) underwent 20 6-hour recordings of MII, breathing movements, nasal airflow, electrocardiogram, pulse oximeter saturation, and pulse waveforms. MII signals were analyzed, independent of CR signals, for reflux episodes (RE), defined as a fall in impedance in at least the 2 most distal channels. CR signals were analyzed for CR events, ie, apneas of >/=4-second duration, desaturations to /=37 weeks' gestation) with moderate or severe newborn encephalopathy and 564 unmatched term control subjects. The Griffiths Mental Development Scales was used to ascertain developmental status and a General Quotient (GQ) score. Outcome measures were the Griffiths developmental subscales, GQ, diagnosis of cerebral palsy, and mortality. RESULTS: Thirty-four patients and 1 control subject died before reaching assessment. Between June 1994 and December 1999, 195 (81%) eligible patients and 445 (79%) eligible control subjects were assessed. Statistically significant differences were found between patients and control subjects for GQ and all developmental subscales. Overall, 39% of patients had a poor outcome as defined by death, cerebral palsy, or a significant degree of developmental delay, compared with 2.7% of control subjects. Furthermore, 62% of those with severe encephalopathy had a poor outcome compared with 25% of those with moderate encephalopathy. Patients with a history of seizures were 3 times more likely to develop cerebral palsy than patients without. Overall, 28 (10.1%) of patients have cerebral palsy. CONCLUSIONS: These data provide important prognostic information regarding survival and serious disability and indicate that newborn encephalopathy places children at significant risk of developmental delay by their second year. These findings also suggest that comprehensive clinical and educational assessments are required to enable appropriate educational provisions as these infants approach school entry. PMID- 11773539 TI - Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. AB - OBJECTIVE: Nosocomial infections are a serious problem among very low birth weight (VLBW) infants. We studied the association between late-onset sepsis (LOS) and mortality and morbidity in VLBW infants. Methods. From a national cohort of 5555 VLBW infants born in Israel during 1995 through 1998, 4829 survived at least 3 days and composed the study population. Maternal, perinatal, or postnatal variables that showed a significant association with LOS in a univariate analysis were tested in a bivariate analysis (adjusted for gestational age). Variables with P /=7 days. RESULTS: A total of 8443 children with a primary hospital diagnosis of DKA and 123 children with type 1 DM and coma were identified; 55% of the children were girls, 32% were nonwhite, 29% received Medicaid insurance, and 33% resided in areas of poverty. Children with prolonged hospital stay were significantly more likely to be of nonwhite race (odds ratio [OR]: 2.0; 95% confidence interval [CI]: 1.6-2.5), to receive Medicaid insurance (OR: 1.4; 95% CI: 1.1-1.7), to live in areas of poverty (OR: 1.3; 95% CI: 1.1-1.7), and to be of younger age. CONCLUSIONS: When compared with state census data, nonwhite and poor children were more likely to be admitted with complications of DM and to have significantly prolonged and expensive hospital stays. These children should be targeted for intensive diabetes education and outpatient medical support both to improve their health and potentially to decrease total health care costs. PMID- 11773541 TI - Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. AB - OBJECTIVE: To present a clinical version of the 2000 Centers for Disease Control and Prevention (CDC) growth charts and to compare them with the previous version, the 1977 National Center for Health Statistics (NCHS) growth charts. METHODS: The 2000 CDC percentile curves were developed in 2 stages. In the first stage, the empirical percentiles were smoothed by a variety of parametric and nonparametric procedures. To obtain corresponding percentiles and z scores, we approximated the smoothed percentiles using a modified LMS estimation procedure in the second stage. The charts include of a set of curves for infants, birth to 36 months of age, and a set for children and adolescents, 2 to 20 years of age. RESULTS: The charts represent a cross-section of children who live in the United States; breastfed infants are represented on the basis of their distribution in the US population. The 2000 CDC growth charts more closely match the national distribution of birth weights than did the 1977 NCHS growth charts, and the disjunction between weight-for-length and weight-for-stature or length-for-age and stature-for-age found in the 1977 charts has been corrected. Moreover, the 2000 CDC growth charts can be used to obtain both percentiles and z scores. Finally, body mass index-for-age charts are available for children and adolescents 2 to 20 years of age. CONCLUSION: The 2000 CDC growth charts are recommended for use in the United States. Pediatric clinics should make the transition from the 1977 NCHS to the 2000 CDC charts for routine monitoring of growth in infants, children, and adolescents. PMID- 11773542 TI - Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. AB - OBJECTIVE: To identify predictors of central precocious puberty (CPP) that reveal central nervous system (CNS) abnormalities in girls with CPP. METHODS: A retrospective cohort study was conducted of all girls younger than 8 years with breast development related to CPP, seen between 1982 and 2000, in a university pediatric hospital in Paris, France. For a pilot population (186 idiopathic, 11 revealing CNS abnormalities), the accuracy of the Lawson Wilkins Pediatric Endocrine Society recommendations were evaluated. Potential clinical, radiological, and biological predictors of CNS abnormalities were assessed by univariate and multivariate analyses. A diagnosis tree aiming for 100% sensitivity for the detection of CNS abnormalities was constructed and was tested on a validation population (39 idiopathic, 3 revealing CNS abnormalities). RESULTS: Applying the Lawson Wilkins Pediatric Endocrine Society recommendations, 2 of 11 girls with CPP that revealed CNS abnormalities would not have been considered to require brain imaging. Independent predictors of CNS abnormalities were age at onset of puberty <6 years (adjusted odds ratio [AOR]: 6.7; 95% confidence interval [CI]: 1.5-29), lack of pubic hair at diagnosis (AOR: 7.7; 95% CI: 1.8-33), and estradiol >110 pmol/L (AOR: 4.1, 95% CI: 1.0-17). The diagnosis tree that was constructed on the basis of these predictors had 100% sensitivity and 56% specificity for the validation population. CONCLUSION: The identification of girls who have CPP and require cerebral imaging seems possible on the basis of validated, simple, and reproducible predictors: age and estradiol. However, this process needs to be tested on other populations. PMID- 11773543 TI - Heliox therapy in infants with acute bronchiolitis. AB - OBJECTIVE: To assess the therapeutic effects of breathing a low-density gas mixture (heliox: 70% helium and 30% oxygen) in infants with bronchiolitis. DESIGN: Prospective, interventional, comparative study. SETTING: A pediatric intensive care unit (PICU) in a tertiary care, teaching hospital. PATIENTS: Thirty-eight infants, 1 month to 2 years old, consecutively admitted to the PICU for treatment of moderate-to-severe acute respiratory syncytial virus bronchiolitis. INTERVENTIONS: The first 19 patients were enrolled as the control group and received supportive care and nebulized epinephrine. In the next 19 patients, heliox therapy was added through a nonrebreather reservoir face mask. Measurements and Outcomes. Respiratory distress score, respiratory rate, heart rate, end-tidal CO(2) (etCO(2)), and pulse oximetry oxygen saturation (satO(2)) values were recorded at baseline and at regular intervals. Data obtained during the first 4 hours were analyzed for comparison purposes. Demographic data, age, time elapsed from the start of the symptoms to the admission to PICU, length of stay in PICU (PICU-LOS), and duration of heliox therapy were also collected for each patient. Reductions in clinical scores and PICU-LOS were considered primary outcomes. Main Results. At baseline, the heliox and control groups had similar age (5.5 +/- 3.1 vs 5.9 +/- 3 months), previous length of course (47.3 +/- 19.3 vs 45.4 +/- 18.6 hours), clinical score (6.7 +/- 1.1 vs 6.6 +/- 1), heart rate (160 +/- 24 vs 165 +/- 20 beats per minute), respiratory rate (64 +/- 7 vs 61 +/- 7 respirations per minute), satO(2) (91 +/- 2.3 vs 91 +/- 2.5%), and etCO(2) (34 +/- 7 vs 33 +/- 6 mm Hg). Clinical score, heart rate, respiratory rate, and satO(2) improved during the study in both groups. After 1 hour, the improvement in clinical score was significantly higher in the heliox group than in the control group (3.6 +/- 1.16 vs 5.5 +/- 0.89), and these differences continued to be significant at the end of the observation period (2.39 +/- 0.69 and 4.07 +/- 0.96, respectively), with a total average decrease in the score of 4.2 points in the heliox group versus 2.5 points in the control group. Heart and respiratory rates were also significantly lower in the heliox group compared with the control group after 1 hour and stayed lower throughout the rest of the study period. No changes were noted either in satO(2) between groups or in etCO(2) within or between groups throughout the study. Mean duration of heliox administration was 53 +/- 24 hours (range: 24-112 hours) and no adverse effects were detected. PICU LOS was significantly shorter in the heliox group (3.5 +/- 1.1 days) than in the control group (5.4 +/- 1.6 days). CONCLUSIONS: In infants with moderate-to-severe respiratory syncytial virus bronchiolitis, heliox therapy enhanced their clinical respiratory status, according to the marked improvement in their clinical scores and the reduction of the accompanying tachycardia and tachypnea. This beneficial response occurred within the first hour of its administration and was maintained as long as heliox therapy continued. In addition, PICU-LOS was reduced in heliox treated patients. Long-term prospective studies are required to corroborate these findings and to establish the proper place of heliox in the therapeutic schedule of bronchiolitis. PMID- 11773544 TI - Long-term consequences of toxic epidermal necrolysis in children. AB - OBJECTIVE: Toxic epidermal necrolysis (TEN) is an acute inflammatory systemic condition that involves injury not just to the skin. Historically, it has been associated with a high mortality but few long-term consequences among survivors. With improved survival, long-term consequences may be becoming more apparent. The objective of this study was to define these long-term consequences and their frequency. METHODS: From July 1, 1991, to June 30, 2000, 11 children with severe TEN were referred to a regional pediatric burn facility. Wounds were managed with a strategy involving prevention of wound desiccation and superinfection, including the frequent use of biological wound coverings. All children survived and have been followed in the burn clinic. The records of all children were reviewed in detail. RESULTS: Two boys and 9 girls with an average age of 7.2 +/- 1.8 years (range: 6 months-15 years) and sloughed surface area of 76 +/- 6% of the body surface (range: 50%-95%) were admitted to the burn unit for care. Antibiotics (3 children), anticonvulsants (4 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were believed to have triggered the syndrome. Six (55%) children required intubation for an average of 9.7 +/- 1.8 days (range: 2-14 days). Mucosal involvement occurred in 10 (91%) and ocular involvement in 10 (91%). Lengths of stay averaged 19 +/- 3 days (range: 6-40 days). Overall follow-up averaged 14 +/- 13 months. Three children had no apparent long-term consequences of the disease and were referred to primary care follow-up after the 2-month burn clinic visit. The remaining children had follow-up averaging 23 +/- 13 months. The most common long-term morbidity involved eyes (3 children [27%]), nails (4 children [36%]), and variegated skin depigmentation (all children). One child developed vaginal stenosis from mucosal inflammation. No esophageal strictures or recurrent TEN has been diagnosed. CONCLUSIONS: Survival has improved in children with TEN, but long term sequelae are not infrequent. The most common long-term consequences involve the eyes, the skin, and the nails. PMID- 11773545 TI - Neonatal antibody titers against varicella-zoster virus in relation to gestational age, birth weight, and maternal titer. AB - OBJECTIVE: Varicella-zoster virus (VZV) can cause severe disease in premature neonates. The fetus receives protective maternal VZV-immunoglobulin G (IgG) mainly in the third trimester of pregnancy. Therefore, premature neonates are considered at risk for VZV infection. Administration of varicella-zoster immunoglobulin (VZIG) within 96 hours after exposure effectively prevents severe illness in susceptible patients. The objectives of this study were to define the major determinants of the neonatal VZV-IgG titer and to determine the half-life of transplacentally acquired VZV-IgG. Guidelines provided by the Centers for Disease Control and Prevention for the use of VZIG in (premature) neonates were evaluated. METHODS: VZV-IgG titers were measured in sera of 221 neonates and 43 mothers using a quantitative enzyme-linked immunosorbent assay. In 27 neonates, VZV-IgG titers were followed for up to 14 weeks. RESULTS: In a linear regression model, the maternal antibody titer was the major determinant of the neonatal titer (beta = 0.89); gestational age was only of minor importance (beta = 0.18). The median half-life of VZV-IgG in neonates was 25.5 days (range: 14.6-76.0 days). In the first weeks of life, major fluctuations of the VZV-IgG titer occurred in >50% of the neonates. The predictive value of Centers for Disease Control and Prevention guidelines for identification of neonates who should receive VZIG in case of exposure to VZV was poor: positive and negative predictive values were 0.80 and 0.43, respectively. CONCLUSIONS: The neonatal VZV IgG titer is predominantly predicted by the maternal VZV-IgG titer, whereas birth weight and gestational age are much less predictive than previously reported. PMID- 11773546 TI - Opsoclonus-ataxia caused by childhood neuroblastoma: developmental and neurologic sequelae. AB - OBJECTIVE: Opsoclonus-ataxia, also called "dancing eye syndrome," is a serious neurologic condition that is often a paraneoplastic manifestation of occult neuroblastoma in early childhood. Despite resection of tumor and immunosuppressive therapy, outcome generally includes significant developmental and behavioral sequelae. There is controversy about how treatment alters outcome. The goals of this study were to understand the ongoing neurologic and developmental deficits of children who are treated for opsoclonus-ataxia with associated neuroblastoma; to relate treatment history to outcome; and to quantify objectively the acute changes in motor function, speech, mood, and behavior related to intravenous immunoglobulin (IVIg) treatment. METHODS: Patients were children with opsoclonus-ataxia caused by neuroblastoma, regardless of interval since diagnosis. Records were reviewed, and children underwent comprehensive evaluations, including neurologic examination and tests of cognitive and adaptive function, speech and language, and fine and gross motor abilities. Psychiatric interview and questionnaires were used to assess current and previous behavior. In 6 children, a videotaped standardized examination of eye movements was performed. Additional examinations were performed immediately before and 2 to 3 days after treatment with IVIg in 5 children. RESULTS: Seventeen children, ages 1.75 to 12.62 years, were examined. All had a stage I or II neuroblastoma resected 3 months to 11 years previously. None received any other treatment for the tumor. All but 1 had received at least 1 year of either oral corticosteroids or corticotropin (ACTH); 12 had received 1 or more courses of IVIg, 2 g/kg. Three had received other immunosuppressive treatment, including cyclophosphamide. Cognitive development and adaptive behavior were delayed or abnormal in nearly all children. Expressive language was more impaired than receptive language. Speech was impaired, including both intelligibility and overall output. Fine and gross motor abilities were impaired. Increased age was strikingly associated with lower scores in all areas. Behavioral problems early in the course included severe irritability and inconsolability in all; later, oppositional behavior and sleep disorders were reported. Opsoclonus abated in all, but abnormalities in pursuit eye movements were found in all 6 children cooperative with standardized examination. Outcome did not differ in children who were treated with ACTH versus oral steroids. Three children who had received cyclophosphamide fared poorly. Immediate versus delayed treatment was not associated with better outcome. IVIg improved both gross and fine motor and speech function acutely, but we could not confirm long-term benefit of IVIg. Total number of courses of IVIg was not associated with outcome. CONCLUSIONS: Opsoclonus-ataxia caused by neuroblastoma causes substantial developmental sequelae that are not adequately prevented by current treatment. The increased deficits in older children raise concern that this represents a progressive encephalopathy rather than a time-limited single insult. Although the study is cross-sectional and neither randomized nor blinded, we were unable to confirm a purported advantage of either ACTH over corticosteroids or of cyclophosphamide. A randomized study is needed but is difficult for this rare condition. PMID- 11773547 TI - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: clinical presentation and follow-up of 50 patients. AB - OBJECTIVES: To assess the mode of presentation, biochemical abnormalities, clinical course, and effects of therapy in patients of long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. BACKGROUND: LCHAD deficiency is a rare, autosomal recessive inborn error of fatty acid oxidation. Although case reports and small series of patients have been published, these may not give a true picture of the clinical and biochemical spectrum associated with this disorder. To improve the early recognition and management of this potentially lethal disorder, we have reviewed a large cohort of LCHAD-deficient patients. METHODS: A questionnaire was sent to the referring physicians of 61 unselected patients with LCHAD deficiency diagnosed in our center. The standardized questionnaire requested information about the clinical signs and symptoms at presentation, the clinical history, family history, pregnancy, biochemical parameters at presentation, treatment, and clinical outcome. RESULTS: Questionnaires on 50 patients (82%) were returned and included in this study. The mean age of clinical presentation was 5.8 months (range: 1 day-26 months). Seven (15%) of the patients presented in the neonatal period. Thirty-nine patients (78%) presented with hypoketotic hypoglycemia, the classical features of a fatty acid oxidation disorder. Eleven patients (22%) presented with chronic problems, consisting of failure to thrive, feeding difficulties, cholestatic liver disease, and/or hypotonia. In retrospect, most (82%) of the patients presenting with an acute metabolic derangement also suffered from a combination of chronic nonspecific symptoms before the metabolic crises. Mortality in this series was high (38%), all dying before or within 3 months after diagnosis. Morbidity in the surviving patients is also high, with recurrent metabolic crises and muscle problems despite therapy. CONCLUSIONS: LCHAD deficiency often presents with a combination of chronic nonspecific symptoms. Early diagnosis is difficult in the absence of the classical metabolic derangement. Survival can be improved by prompt diagnosis, but morbidity remains alarmingly high despite current therapeutic regimes. PMID- 11773548 TI - Postnatal management of resolving fetal lung lesions. AB - OBJECTIVES: Lung lesions are increasingly diagnosed since the advent of routine prenatal ultrasound. These lesions seem to involute in 15% to 30% of cases. Postnatal evaluation is frequently limited, particularly when repeated ultrasound or initial chest radiographs are normal. As careful follow-up or resection may be required, accurate diagnosis is essential. The objective of this study was to determine whether prenatal lung lesions that seem to resolve are still present when evaluated more closely. METHODS: We followed 24 cases of prenatally diagnosed lung lesions at our center, using repeated chest radiographs and chest computerized tomography (CT). RESULTS: Some lesions caused mild mediastinal shift, but none showed hydrops fetalis. In 7 cases, the last prenatal ultrasound was negative. In 15 cases, initial postnatal chest radiograph was normal and in only 4 of these, the lesion was seen on later chest radiographs. This apparently high rate of resolution was, however, misleading. In 22 of the 23 cases in which CT was performed, lung cysts or lobar overinflation was clearly demonstrated. CONCLUSIONS: Apparent involution of lung lesions on serial prenatal ultrasounds or neonatal chest radiograph can be misleading. We strongly recommend repeated radiographs and chest CT for definitive diagnosis in all cases. PMID- 11773549 TI - Current treatment of juvenile rheumatoid arthritis. AB - Prognostic factors in juvenile rheumatoid arthritis (JRA) include polyarticular onset, polyarticular disease course, and rheumatoid factor positivity; in the systemic onset subtype, persistence of systemic features at 6 months after onset confers a worse prognosis. Timely diagnosis and appropriate aggressive treatment of patients with poor prognostic features improve quality of life and outcome. After nonsteroidal anti-inflammatory drugs, methotrexate is the most commonly used second-line agent. However, approximately one third of patients do not respond to methotrexate adequately. Randomized, placebo-controlled, clinical trials in patients with JRA are few, but one such trial with the tumor necrosis factor inhibitor etanercept shows that this drug is effective and well-tolerated. Other recently approved agents for rheumatoid arthritis, including infliximab, leflunomide, celecoxib, and rofecoxib, have not been adequately studied in pediatric patients, and the role of these agents in children with JRA remains to be determined. PMID- 11773550 TI - Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. AB - The National Institute of Neurological Disorders and Stroke and the Office of Rare Disorders sponsored a workshop on perinatal and childhood stroke in Bethesda, Maryland, on September 18 and 19, 2000. This was an international workshop to bring together experts in the field of perinatal and childhood stroke. Topics covered included epidemiology, animal models, risk factors, outcome and prognosis, and areas of future research for perinatal and childhood stroke. Stroke in infants and children is an important cause of morbidity and mortality and an emerging area for clinical and translational research. Currently, there is no consensus on the classification, evaluation, outcome measurement, or treatment of perinatal and childhood stroke. Pediatric stroke registries are needed to generate data regarding risk factors, recurrence, and outcome. The impact of maternal and perinatal factors on risk and outcome of neonatal stroke needs to be studied. This information is essential to identifying significant areas for future treatment and prevention. PMID- 11773551 TI - Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system? AB - Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant's immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago. PMID- 11773552 TI - Precocious puberty in girls and the risk of a central nervous system abnormality: the elusive search for diagnostic certainty. PMID- 11773553 TI - Childhood growth charts. PMID- 11773554 TI - Politics and reading at the National Institute of Child Health and Human Development. PMID- 11773555 TI - Developmental surveillance and screening of infants and young children. PMID- 11773556 TI - Activated charcoal in the home: helpful and important or simply a distraction? PMID- 11773557 TI - Privacy rights, HIPAA, and the AAP: about right; about time. PMID- 11773558 TI - An integrated approach to the diagnosis and prospective management of partial ornithine transcarbamylase deficiency. AB - Ornithine transcarbamylase deficiency (OTCD) is the most common inherited urea cycle disorder, and is transmitted as an X-linked trait. Female OTCD heterozygotes exhibit wide clinical severities, ranging from being apparently asymptomatic to having the profound neurologic impairment observed in affected males. However, clinical and laboratory diagnosis of partial OTCD during asymptomatic periods is difficult, and correlation of phenotypic severity with either DNA mutation and/or in vitro enzyme activity is imprecise. Provocative testing, including protein load and allopurinol challenge used in the diagnosis of OTCD females, is not without risk and subject to both false positives and negatives. Although definitive when successful, DNA-based diagnosis is unable to detect mutations in all cases. We have previously used the ratio of isotopic enrichments of [(15)N]urea/[(15)N]glutamine ((15)N-U/G) derived from physiologic measurements of ureagenesis by stable isotope infusion as a sensitive index of in vivo urea cycle activity. We have now applied this method in combination with traditional biochemical testing to aid in the diagnosis of a symptomatic OTCD female in whom mutation in the ornithine transcarbamylase (OTC) gene was not found. The (15)N-U/G ratio in this patient showed that she had severe reduction of in vivo urea cycle activity on par with affected male subjects. This was correlated with partially deficient OTC activity in her liver, degree of orotic aciduria, and history of suspected recurrent hyperammonemic episodes before age 3. The measurement of in vivo urea cycle activity in combination with traditional biochemical indices optimizes a diagnostic approach to the at-risk partial OTCD patient, especially in those in whom molecular testing is unproductive. Together they contribute to the risk versus benefit considerations regarding the pursuit of medical therapy versus surgical, ie, orthotopic liver transplantation (OLT) therapy. The decision to resort to OLT in females with partial OTC activity is controversial, requiring consideration of phenotypic severity, failure of medical therapy, access to tertiary care centers experienced in the management of acute hyperammonemia, and social factors. In this patient, the use of in vivo and in vitro measures of urea cycle activity in conjunction with a consideration of her clinical history and medical-social situation led to a decision for OLT. PMID- 11773559 TI - Infective endocarditis successfully treated in extremely low birth weight infants with recombinant tissue plasminogen activator. AB - Increased survival of extremely low birth weight infants depends on the use of indwelling catheters. These catheters expose the infant to the risk of thrombus formation and line infection. When intracardiac thromboses become infected, the entity is indistinguishable from infective endocarditis and exposes the infant to prolonged sepsis and risk of disseminated infected emboli. Despite prolonged antiinfective therapy and removal of the infected line, resolution of the sepsis and dissolution of the vegetations is frequently not achieved. We describe 2 cases of infective endocarditis in extremely low birth weight infants successfully treated with recombinant tissue plasminogen activator in addition to prolonged antiinfective therapy. Blood cultures became sterile and vegetations disappeared within days of commencing treatment, and there were no systemic complications. A literature search detailed in the article confirms the poor outcome associated with infectious endocarditis in preterm infants. Tissue plasminogen activator may play an important role when standard care has failed. PMID- 11773560 TI - Use of inhaled nitric oxide during interhospital transport of newborns with hypoxemic respiratory failure. PMID- 11773561 TI - Recommended childhood immunization schedule-United States, 2002. PMID- 11773562 TI - Nasal saline for acute sinusitis. PMID- 11773563 TI - The role of uroradiological studies in children with renal abscess. PMID- 11773564 TI - The sinusitis debate. PMID- 11773565 TI - Swimming programs for infants and toddlers. PMID- 11773566 TI - Best start breastfeeding promotion campaign. PMID- 11773567 TI - Leukotriene modifiers. PMID- 11773568 TI - MMR--Separate administration-has it been done? PMID- 11773569 TI - Impact of site of care, race, and Hispanic ethnicity on medication use for childhood asthma. AB - OBJECTIVE: To understand the importance of source of care and other factors that influence differences in asthma medication use by race and Hispanic ethnicity. METHODS: The Childhood Asthma Severity Study provided 12-month, retrospective, parent-reported questionnaire data on a monthly basis for children ages /=5 days were eligible. Within these patients, we identified all cases of radiologically confirmed thrombosis. Cases of thrombosis were reviewed for fulfillment of clinical HIT criteria. HIT-associated thrombosis was confirmed serologically by determination of levels of antibodies against heparin/platelet factor 4 complexes. RESULTS: Of 1950 children admitted during the study period, 612 were exposed to heparin for >/=5 days. Thrombosis occurred in 57 patients (9.3%). Plasma samples were available for 38 cases, of which 14 satisfied clinical HIT-criteria. Calculated incidence rate for HIT-associated thrombosis: 2.3%, (95% confidence interval: 1.3%-3.9%, for patients exposed to heparin >/=5 days). Nine patients suffered from venous, 2 patients from arterial, and 3 had combined arterial and venous thrombosis. None of the 14 patients died or underwent amputation. Six patients had heparin and platelet factor 4-complex antibody levels above the cutoff level for adults. The remaining 8 patients had significantly higher antibody levels than a matched control group. CONCLUSION: Compared with that reported for adults, HIT-associated thrombosis in pediatric intensive care unit patients has a similar incidence but a less severe outcome. PMID- 11773579 TI - Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. AB - OBJECTIVE: To extend the information base on the hepatobiliary manifestations of neonatal lupus erythematosus (NLE) with regard to frequency of occurrence, clinical characteristics, and outcome. METHODS: Review of records from the Research Registry for Neonatal Lupus. RESULTS: Nineteen (9%) of 219 patients who had NLE and were enrolled in a national registry had probable or possible NLE hepatobiliary disease. In 16 cases, hepatobiliary disease occurred in addition to cardiac or cutaneous NLE. In 3 cases, hepatobiliary disease occurred as the sole clinical manifestation of NLE. Three clinical variants of hepatobiliary disease were observed: 1) severe liver failure present during gestation or in the neonatal period, often with the phenotype of neonatal iron storage disease; 2) conjugated hyperbilirubinemia with mild or no elevations of aminotransferases, occurring in the first few weeks of life; and 3) mild elevations of aminotransferases occurring at approximately 2 to 3 months of life. The prognosis for the children in the last 2 categories is excellent. CONCLUSIONS: Hepatobiliary disease is a relatively common finding in NLE and can be the sole clinical manifestation of NLE. Clinicians should be aware of the broad range of hepatobiliary disease that may occur in children with NLE. PMID- 11773580 TI - Intracranial hemorrhage in infants and children with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). AB - OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Most cases are caused by mutations in the endoglin gene on chromosome 9 (HHT type 1) or the activin receptor-like kinase 1 gene on chromosome 12 (HHT type 2), which leads to telangiectases and arteriovenous malformations (AVM) of the skin, mucosa, and viscera. Epistaxis is the most frequent presentation. Visceral involvement includes pulmonary, gastrointestinal, and cerebral AVMs, which have been reported predominantly in adults. The purpose of this article is to describe 9 children who presented with intracranial hemorrhage (ICH) secondary to cerebral AVM. None of these children was suspected of having HHT before the incident, despite family histories of the disease. METHODS: We report the first case of an ICH secondary to a cerebral AVM in a neonate confirmed to have HHT type 1 by molecular analysis. We also describe a series of 8 additional cases of ICH secondary to cerebral AVM in children presumed to have HHT. Examination of multiple affected members from each of these families, using well-accepted published criteria, confirmed the diagnosis of HHT. In addition, genetic linkage studies and/or mutation analysis identified endoglin as the disease-causing gene in 6 of these families. Autopsy, imaging studies, and/or surgery confirmed the presence of cerebral AVMs and ICH in all 9 cases. CONCLUSION: Our report shows that infants and children with a family history of HHT are at risk for sudden and catastrophic ICH. A preemptive diagnosis may potentially identify and prevent more serious sequelae. PMID- 11773581 TI - Increased prevalence of mutations in the cystic fibrosis transmembrane conductance regulator in children with chronic rhinosinusitis. AB - OBJECTIVE: Chronic rhinosinusitis results in significant morbidity in the pediatric population; however, no predisposing factor is found in many cases. Cystic fibrosis (CF) is a recognized cause of chronic rhinosinusitis. Although the carrier frequency for CF ranges from 3% to 4% in the general white population, the prevalence of mutations in the CF transmembrane conductance regulator (CFTR) among children with chronic rhinosinusitis is unknown. Our objective was to study the frequency of CFTR mutations among children with chronic rhinosinusitis. METHODS: Fifty-eight white children who were from the St Louis metropolitan area and had chronic rhinosinusitis, none of whom satisfied diagnostic criteria for CF, underwent sweat testing and genotyping for CFTR mutations using an assay that detects 90% of mutations seen in this ethnic group. RESULTS: Seven of the 58 patients (12.1%) tested harbored CFTR mutations as compared with the expected rate of 3% to 4% in this ethnic group. Five patients had the DeltaF508, 1 had the R117H, and 1 had the I148T mutation. Only 1 of the 7 children had a borderline abnormal sweat test. Two of the 58 patients experienced recurrent Pseudomonas aeruginosa rhinosinusitis, and both were DeltaF508 heterozygotes. Three other children with no detectable CFTR mutation had borderline elevated sweat-test results. The CFTR intron 8 5T polymorphism was found at a frequency comparable to that reported for the general population. CONCLUSION: There is an increased occurrence of CFTR mutations in children who have chronic rhinosinusitis and do not meet diagnostic criteria for CF, usually in the setting of a normal sweat chloride. These results suggest a role for CFTR mutations in predisposition to chronic rhinosinusitis. PMID- 11773582 TI - Group a streptococcus spinal epidural abscess during varicella. AB - Multiple complications of varicella have been described. Musculoskeletal complications (osteomyelitis, septic arthritis, and necrotizing fasciitis) as well as neurologic complications (ataxia, encephalitis, and transverse myelitis) are well-known. We describe the cases of 2 children, ages 18 months and 5 years, who were admitted recently to 2 pediatric hospitals in Montreal with a resolving varicella, abdominal and lumbar pain, and a refusal to walk and in whom a diagnosis of epidural abscess caused by group A streptococcus (GAS) was established. No previous case of epidural abscess caused by GAS in the context of varicella has been reported. Epidural abscesses are rare in pediatrics and are caused mainly by hematogenous spread of Staphylococcus aureus. The diagnosis in pediatrics is challenging because it is rare and does not present as classically as in adults. The prognosis is related to the presence of neurologic deficits before surgery and to the rapidity with which the diagnosis and the intervention are made. These cases highlight a new clinical association in children of epidural abscess caused by GAS and varicella. An early clinical diagnosis requires a high index of suspicion when back or abdominal pain with or without neurologic signs and symptoms occurs during or soon after varicella. PMID- 11773583 TI - Venous air embolism during home infusion therapy. AB - Venous air embolism (VAE) is a potential complication of surgical procedures as well as central venous access. There are several reports in the literature of VAE during the in-hospital use and placement of central venous access. However, we are unaware of previous cases of VAE in children who received home infusion therapy via central venous access. We report the occurrence of a VAE in a 2-year old with a Broviac catheter for home intravenous antibiotic therapy. VAE occurred when a bolus of air was unintentionally administered as the mother removed the cassette from the pump when it was alarming air in line. The cassette and tubing had been placed into the pump without a fluid flush. After the tubing and cassette were removed from the pump, the air in the line was allowed to flow by gravity into the patient, resulting in the immediate onset of respiratory and neurologic symptoms. The mother administered 2 rescue breaths, and the child's color and breathing returned to normal over the next 2 minutes. After the child arrived in the emergency department, the child's mental status returned to normal and the remainder of her physical examination was unremarkable. She had an uneventful recovery and was discharged from the hospital the following day. Additional antibiotic administration was accomplished in the emergency department of a local hospital. VAE can occur spontaneously when there is an open venous structure 5 cm or more above the heart or if air is delivered under pressure into the venous system, such as during a laparoscopy or mishaps with infusion bags. The morbidity and mortality of VAE are related to the volume of air, rate of entrainment, the patient's underlying cardiorespiratory status, and the patient's position. Morbidity and mortality occur as a consequence of right ventricular outflow obstruction or end-organ dysfunction from left-sided obstruction of coronary or cerebral vasculature as air passes across a patent foramen ovale or through the pulmonary circulation. Of all the literature pertaining to VAE with central lines, there are no previous reports of VAE occurring during home infusion therapy in children. With managed care requiring shorter hospitalizations and more children being discharged from the hospital on home infusion therapy, parents and lay caregivers are being asked to administer medications and perform routine maintenance on central venous devices. In our case, despite the fact that the mother had been educated regarding the appropriate technique for medication administration, she forgot to purge the air from the line before connecting the tubing and administering the antibiotic. Although the infusion pump will alarm when there is air in the line, it detects air only in a small part of the line and this safety feature is not in play if the device is removed from the infusion pump and administered via gravity. If such safety precautions are not adhered to, then the volume of air that fills the intravenous tubing from the drip chamber to the patient (25-30 mL in the pediatric infusion pump tubing used in our patient) can be infused by gravity into the patient's venous system. Because the consequences of VAE are so severe, the focus should be on prevention. Pumps used for home infusion therapy should have appropriate alarms to alert caregivers to the presence of air in the line. Obviously, this will not totally prevent this complication as this type of pump was used in our patient. It is crucial to educate caregivers of patients with central venous access regarding the hazards of VAE and safety measures to prevent it. With the increased use of home infusion therapy, ongoing evaluations of complications related to this form of therapy are mandatory so that there is continued evaluation of practices and appropriate changes made when necessary to increase further the safety of these techniques. PMID- 11773584 TI - Testicular torsion in an adolescent with Fragile X Syndrome. AB - Fragile X syndrome (FraX) is the most common hereditary form of mental retardation. The clinical syndrome includes mental retardation, macroorchidism, and typical but variable facial features. Although macroorchidism has been recognized as a cardinal feature of FraX, descriptions of testicular pathology are rare. Testicular torsion is a relatively common surgical emergency in young men, peaking at the onset of puberty when the testes undergo a period of rapid growth. However, testicular torsion has never been associated with macroorchidism. We report the first known case of testicular torsion in a 14-year old boy with FraX and macroorchidism. Although we are unable to establish a definitive relationship between macroorchidism and testicular torsion in an isolated case report, primary care takers of children with macroorchidism should be aware of this occurrence. We recommend measurement of testicular volume during annual evaluations of children and adolescents with macroorchidism. Acute scrotal pain or increased testicular volume should be promptly evaluated. PMID- 11773585 TI - Partial hypoxanthine-Guanine phosphoribosyltransferase deficiency as the unsuspected cause of renal disease spanning three generations: a cautionary tale. AB - Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency: complete HPRT deficiency (Lesch-Nyhan syndrome) presenting with severe neurologic or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. A 3 generation kindred is described in which the recognition of partial HPRT deficiency in 2 adolescent male siblings presenting with uric acid lithiasis led to the diagnosis in 2 maternal uncles already in renal failure of unknown cause. This report highlights the importance of clinical awareness leading to early diagnosis, appropriate diagnostic methodology, and therapy of a treatable inherited disorder of purine metabolism for the prevention of renal failure. PMID- 11773586 TI - Use of real-time magnetic resonance guidance to assist bone biopsy in pediatric malignancy. AB - Magnetic resonance (MR) imaging (MRI) has the advantage of demonstrating lesions not visualized by other radiologic modalities. We present a case involving pediatric malignancy where MR-guided bone biopsy confirmed correct histologic diagnosis and was used to plan additional treatment. A 2-year, 9-month-old boy had a history of spontaneous regression of stage 4S neuroblastoma. (123)I metaiodobenzylguanidine scintigraphy showed a hot spot at his right lower leg; however, neither plain radiograph (99m)Tc diphosphonate bone scan was positive. Only MRI depicted a lesion at the distal third of his right tibia, and a subsequent MR-guided bone biopsy was diagnostic of bone marrow metastasis. After 6 courses of intensive chemotherapy, he has been in complete remission. MR-guided biopsy technique is likely to be particularly useful for the resection of invisible metastatic lesions, especially those that are only visible using MRI. PMID- 11773587 TI - SIDS, ALTE, apnea, and the use of home monitors. PMID- 11773588 TI - Vertigo. PMID- 11773589 TI - Effects of certain prenatal drugs on the fetus and newborn. PMID- 11773590 TI - Index of suspicion. PMID- 11773591 TI - Head lice. PMID- 11773592 TI - Physiological Genomics: Who we are and where we're going. PMID- 11773593 TI - Analysis of the sheep genome. AB - The identification of genes controlling several traits of interest in sheep has been accomplished by positional candidate cloning. In these studies, the trait is first mapped to a specific chromosomal region by linkage analysis, which requires families that are segregating for the trait and for polymorphic markers. Microsatellite markers are usually used for these analyses because of their extensive genetic variability. Once the location of a trait is determined by linkage to the markers, possible candidate genes controlling the trait can be inferred because of their proximity to linked markers. It is not necessary to map all possible genes in sheep for this strategy to be effective. Rather, a subset of genes that are mapped in humans and mice have also been mapped in sheep; these genes serve as "anchors" across the comparative maps of the different species. Further study of these positional candidates has revealed naturally occurring mutations that produce phenotypes that are unique to sheep. Thus the genetic analysis of sheep traits advances knowledge not only in this species but provides critical information for understanding biological pathways in mammalian species. PMID- 11773594 TI - Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb? AB - This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal hyperplasia and confer myocardial protection was presented, and it was found that augmenting local nitric oxide (NO) production using gene transfer (GT) of NO synthase or interruption of cell cycle progression through a genetic transfer of cell cycle regulatory genes limited vascular smooth muscle hyperplasia in animal models and infra-inguinal bypass patients. The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed. In addition, experimental evidence was presented that genetic manipulation of peptide systems (i.e., the renin-angiotensin II system and the kallikrein-kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure. Although, as of yet, there are no well controlled human trials proving the clinical benefits of gene therapy for cardiovascular diseases, the data presented here in animal models and in human subjects show that genetic targeting is a promising and encouraging modality, not only for the treatment and long-term control of cardiovascular diseases, but for their prevention as well. PMID- 11773595 TI - Further defining housekeeping, or "maintenance," genes Focus on "A compendium of gene expression in normal human tissues". PMID- 11773596 TI - A compendium of gene expression in normal human tissues. AB - This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology. PMID- 11773597 TI - Identification of AKT-regulated genes in inducible MERAkt cells. AB - AKT/protein kinase B plays a critical role in the phosphoinositide 3-kinase (PI3 kinase) pathway regulating cell growth, differentiation, and oncogenic transformation. Akt1-regulated genes were identified by cDNA array hybridization analysis using an inducible AKT1 protein, MERAKT. Treatment of MERAkt cells with estrogen receptor ligands resulted in phosphorylative activation of MERAKT. Genes differentially expressed in MERAkt/NIH3T3 cells treated with tamoxifen, raloxifene, ICI-182780, and ZK955, were identified at 3 and 20 h. AKT activation resulted in the repression of c-myc, early growth response 1 (EGR1), transforming growth factor beta receptor III (TGF-betar III), and thrombospondin-1 (THBS1). Although c-myc induction is often associated with oncogenic transformation, the c myc repression observed here is consistent with the anti-apoptotic function of AKT. Repression of THBS1 and EGR1 is consistent with the known pro-angiogenic functions of AKT. AKT-regulated genes were found to be largely distinct from platelet-derived growth factor-beta (PDGFbeta)-regulated genes; only T-cell death associated gene 51 (TDAG51) was induced in both cases. In contrast to their repression by AKT, c-myc, THBS1, and EGR1 were induced by PDGFbeta, indicating negative interference between elements upstream and downstream of AKT1 in the PDGFbeta signal transduction pathway. PMID- 11773598 TI - Heart transplantation changes the expression of distinct gene families. AB - We took advantage of the combination of a rat heart transplantation model with a modified differential display RT-PCR method to identify transcriptome changes in the right atria from transplanted compared with native hearts. Based on sequence homology search, the 37 cDNAs differentially displayed both 2 and 7 days posttransplantation were categorized into 7 unknown transcripts, 16 expressed sequence tags (ESTs), and 14 partially or completely characterized genes. The last group cDNAs, validated by relative RT-PCR, belonged to diverse gene families involved in specific metabolisms, protein synthesis, cell signaling, and transcription. Furthermore, we identified differential transcripts corresponding to denervation and fetal gene reexpression. We found coordinate downregulation of genes involved in energy metabolism and protein synthesis regulation, similar to that reported for senescent skeletal muscle. From these transcriptome changes, we propose that heart transplants and senescent muscles share common molecular mechanisms. PMID- 11773599 TI - Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype. AB - The Oak Ridge polycystic kidney (orpk) mutant mouse model resulted from a transgene insertion into the Tg737 gene and exhibits a pleiotropic syndrome with lesions in the kidney, liver, and pancreas. We found marked differences in the phenotypic expression of the orpk mutation when bred on different genetic backgrounds. In the FVB/N background, the phenotype is very severe for kidney, pancreas, and liver lesions. To evaluate better how genetic background might influence the expressivity of the orpk phenotype, we bred the transgene into the C3HeB/FeJLe (C3H) genetic background. We performed a genome-wide scan using backcross and intercross populations with more than 150 markers to map the chromosomal location of the modifier genes that differ in the FVB/N and C3H genetic backgrounds that affect the severity of kidney disease in the orpk mouse. Low-resolution interval mapping was performed using the Map Manager QTb program, with the interval explaining a significant portion of the variance being the distal end of chromosome 4. PMID- 11773600 TI - Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization. AB - Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization. Physiol Genomics 7: 135-148, 2001. First published September 21, 2001; 10.1152/physiolgenomics.00061.2001.-Human decidual fibroblasts undergo a differentiative commitment to the acquisition of endocrine, metabolic, and structural cell functions in a process known as decidualization. Decidualization is critical for embryo implantation and placental function. We characterized gene expression pattern kinetics during decidual fibroblast differentiation by microarray analysis. Of 6,918 genes analyzed, 121 genes were induced by more than twofold, 110 were downregulated, and 50 showed biphasic behavior. Dynamically regulated genes were could be fit into nine K-means algorithm-based kinetic pattern groups, and by biologic classification, into five categories: cell and tissue function, cell and tissue structure, regulation of gene expression, expressed sequence tag (EST), and "function unknown." Reprogramming of genes within specific functional groups and gene families was a prominent feature that consisted of simultaneous induction and downregulation of a set of genes with related function. We previously observed a conceptually similar process during fetal trophoblast differentiation, in which the same phenomena applied to different genes. Of the 569 dynamically regulated genes regulated by either model, only 81 of these were in common. These results suggest that reprogramming of gene expression within focused functional categories represents a fundamental aspect of cellular differentiation. PMID- 11773602 TI - Influence of ethanol on thermoregulation: mapping quantitative trait loci. AB - The genetic basis for the effects of ethanol on thermoregulation was investigated by utilizing recombinant inbred mouse strains from C57BL/6J and DBA/2J progenitor strains. Changes in core body temperature (T(c)) and the degree of fluctuation of T(c) were monitored in male mice following the administration of ethanol in an environment with cyclic changes in ambient temperature (T(a)). Changes in T(c) were utilized to assess ethanol-induced effects on regulated T(c), whereas fluctuations in T(c) were utilized to assess thermoregulatory disruption. Ethanol was administered intraperitoneally at 1.5, 2.5, and 3.5 g/kg for all strains. Change in T(c) and increase in tail temperature were also evaluated at 2.5 g/kg ethanol in a constant T(a) of 26 degrees C. Associations between the measured physiological responses and previously mapped genetic markers were used to identify quantitative trait loci (QTLs). This established probable chromosome locations for a number of genes for the responses. To our knowledge, this is the first report of QTLs that underlie changes in regulation as well as the disruption of a physiological regulatory system. PMID- 11773601 TI - MASH-1/RET pathway involvement in development of brain stem control of respiratory frequency in newborn mice. AB - Respiratory abnormalities have been described in MASH-1 (mammalian achaete-scute homologous gene) and c-RET ("rearranged during transfection") mutant newborn mice. However, the neural mechanisms underlying these abnormalities have not been studied. We tested the hypothesis that the MASH-1 mutation may impair c-RET expression in brain stem neurons involved in the control of breathing. To do this, we analyzed brain stem c-RET expression and respiratory phenotype in MASH-1 +/+ wild-type, MASH-1 +/- heterozygous, and MASH-1 -/- knock-out newborn mice during the first 2 h of life. In MASH-1 -/- newborns, c-RET gene expression was absent in the noradrenergic nuclei (A2, A5, A6, A7) that contribute to modulate respiratory frequency and in scattered cells of the rostral ventrolateral medulla. The c-RET transcript levels measured by quantitative RT-PCR were lower in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ brain stems (P = 0.001 and P = 0.003, respectively). Breath durations were shorter in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ mice (P = 0.022) and were weakly correlated with c-RET transcript levels (P = 0.032). Taken together, these results provide evidence that MASH-1 is upstream of c-RET in noradrenergic brain stem neurons important for respiratory rhythm modulation. PMID- 11773603 TI - Replacement of (alpha)1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity. AB - Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase alpha(1)-subunit (Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP). Currently, two congenic strains, designated S.M5 and S.M6, were made by replacing a segment of the Dahl salt sensitive SS/Jr (S) rat by the homologous region of the Milan normotensive rat (MNS). In S.M5, the gene for Atp1a1 is from the MNS strain; whereas in S.M6, Atp1a1 is from the S strain. The baseline activity of the alpha(1)-Na-K-ATPase and its stoichiometry were evaluated by an assay of ouabain-sensitive inwardly and outwardly directed (86)Rb and (22)Na fluxes in erythrocytes. The two congenic strains showed a similar BP, but both had a BP lower than that of S rats (P < 0.0001). Neither the alpha(1)-Na-K-ATPase activity nor its stoichiometry was affected by the substitution of the Atp1a1 alleles of S by those of MNS. Thus the BP-lowering effects observed in S.M5 and S.M6 could not be attributed to the alpha(1)-Na-K-ATPase activity or its stoichiometry. Atp1a1 is not supported as a candidate to be a BP QTL. PMID- 11773604 TI - Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice. AB - Aquaporin-0 (AQP0), a water transport channel protein, is the major intrinsic protein (MIP) of lens fiber cell plasma membranes. Mice deficient in the gene for AQP0 (Aqp0, Mip) were generated from a library of gene trap embryo stem cells. Sequence analysis showed that the gene trap vector had inserted into the first exon of Aqp0, causing a null mutation as verified by RNA blotting and immunochemistry. At 3 wk of age (postnatal day 21), lenses from null mice (Aqp0( /-)) contained polymorphic opacities, whereas lenses from heterozygous mice (Aqp0(+/-)) were transparent and did not develop frank opacities until approximately 24 wk of age. Osmotic water permeability values for Aqp0(+/-) and Aqp0(-/-) lenses were reduced to approximately 46% and approximately 20% of wild type values, respectively, and the focusing power of Aqp0(+/-) lenses was significantly lower than that of wild type. These findings show that heterozygous loss of AQP0 is sufficient to trigger cataractogenesis in mice and suggest that this MIP is required for optimal focusing of the crystalline lens. PMID- 11773605 TI - Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter. AB - The Wilms' tumor suppressor gene, wt1, encodes a zinc finger transcription factor that can regulate gene expression. It plays an essential role in tumorigenesis, kidney differentiation, and urogenital development. To identify WT1 downstream targets, gene expression profiling was conducted using a cDNA array hybridization approach. We confirm herein that the human vitamin D receptor (VDR), a ligand activated transcription factor, is a WT1 downstream target. Nuclear run on experiments demonstrated that the effect of WT1 on VDR expression is at the transcriptional level. Transient transfection assays, deletion mutagenesis, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays suggest that, although WT1 is presented with a possibility of three binding sites within the VDR promoter, activation of the human VDR gene appears to occur through a single site. This site differs from a previously identified WT1 responsive site in the murine VDR promoter (Maurer U, Jehan F, Englert C, Hubinger G, Weidmann E, DeLucas HF, and Bergmann L. J Biol Chem 276: 3727-3732, 2001). We also show that the products of a Denys-Drash syndrome allele of wt1 inhibit WT1-mediated transactivation of the human VDR promoter. Our results indicate that the human VDR gene is a downstream target of WT1 and may be regulated differently than its murine counterpart. PMID- 11773606 TI - Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss. AB - We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention. PMID- 11773607 TI - Conservation of digestive enzymes. AB - The traditional understanding is that an entirely new complement of digestive enzymes is secreted by the pancreas into the small intestines with each meal. This is thought to be necessary because, like food itself, these enzymes are degraded during digestion. In this review we discuss experiments that bring this point of view into question. They suggest that digestive enzymes can be absorbed into blood, reaccumulated by the pancreas, and reutilized, instead of being reduced to their constituent amino acids in the intestines. This is called an enteropancreatic circulation of digestive enzymes. PMID- 11773608 TI - Immunity, inflammation, and remodeling in the airway epithelial barrier: epithelial-viral-allergic paradigm. AB - The concept that airway inflammation leads to airway disease has led to a widening search for the types of cellular and molecular interactions responsible for linking the initial stimulus to the final abnormality in airway function. It has not yet been possible to integrate all of this information into a single model for the development of airway inflammation and remodeling, but a useful framework has been based on the behavior of the adaptive immune system. In that paradigm, an exaggeration of T-helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli leads to airway inflammatory disease, especially asthma. In this review, we summarize alternative evidence that the innate immune system, typified by actions of airway epithelial cells and macrophages, may also be specially programmed for antiviral defense and abnormally programmed in inflammatory disease. Furthermore, this abnormality may be inducible by paramyxoviral infection and, in the proper genetic background, may persist indefinitely. Taken together, we propose a new model that highlights specific interactions between epithelial, viral, and allergic components and so better explains the basis for airway immunity, inflammation, and remodeling in response to viral infection and the development of long-term disease phenotypes typical of asthma and other hypersecretory airway diseases. PMID- 11773609 TI - Free radicals in the physiological control of cell function. AB - At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish "redox homeostasis." Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical mediated oxidative damage was proposed more than 40 years ago by Harman (J Gerontol 11: 298-300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression. PMID- 11773610 TI - Dendritic cells: immune regulators in health and disease. AB - Dendritic cells (DCs) are bone marrow-derived cells of both lymphoid and myeloid stem cell origin that populate all lymphoid organs including the thymus, spleen, and lymph nodes, as well as nearly all nonlymphoid tissues and organs. Although DCs are a moderately diverse set of cells, they all have potent antigen presenting capacity for stimulating naive, memory, and effector T cells. DCs are members of the innate immune system in that they can respond to dangers in the host environment by immediately generating protective cytokines. Most important, immature DCs respond to danger signals in the microenvironment by maturing, i.e., differentiating, and acquiring the capacity to direct the development of primary immune responses appropriate to the type of danger perceived. The powerful adjuvant activity that DCs possess in stimulating specific CD4 and CD8 T cell responses has made them targets in vaccine development strategies for the prevention and treatment of infections, allograft reactions, allergic and autoimmune diseases, and cancer. This review addresses the origins and migration of DCs to their sites of activity, their basic biology as antigen-presenting cells, their roles in important human diseases and, finally, selected strategies being pursued to harness their potent antigen-stimulating activity. PMID- 11773611 TI - P-450 metabolites of arachidonic acid in the control of cardiovascular function. AB - Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K(+) channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca(2+)-activated K(+) channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue PO(2) both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na(+) transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits. PMID- 11773612 TI - The transporter associated with antigen processing: function and implications in human diseases. AB - The adaptive immune systems have evolved to protect the organism against pathogens encountering the host. Extracellular occurring viruses or bacteria are mainly bound by antibodies from the humoral branch of the immune response, whereas infected or malignant cells are identified and eliminated by the cellular immune system. To enable the recognition, proteins are cleaved into peptides in the cytosol and are presented on the cell surface by class I molecules of the major histocompatibility complex (MHC). The transport of the antigenic peptides into the lumen of the endoplasmic reticulum (ER) and loading onto the MHC class I molecules is an essential process for the presentation to cytotoxic T lymphocytes. The delivery of these peptides is performed by the transporter associated with antigen processing (TAP). TAP is a heterodimer of TAP1 and TAP2, each subunit containing transmembrane domains and an ATP-binding motif. Sequence homology analysis revealed that TAP belongs to the superfamily of ATP-binding cassette transporters. Loss of TAP function leads to a loss of cell surface expression of MHC class I molecules. This may be a strategy for tumors and virus infected cells to escape immune surveillance. Structure and function of the TAP complex as well as the implications of loss or downregulation of TAP is the topic of this review. PMID- 11773613 TI - Aquaporins in the kidney: from molecules to medicine. AB - The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders. PMID- 11773614 TI - Electrolyte transport in the mammalian colon: mechanisms and implications for disease. AB - The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na(+) channels (ENaC), the Na(+)-K(+)-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na(+) feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl( ) secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl(-) channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl(-) secretion and enhanced Na(+) absorption in the colon of cystic fibrosis (CF) patients. Ca(2+)- and cAMP activated basolateral K(+) channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma. PMID- 11773615 TI - Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites. AB - The cytokine macrophage migration inhibitory factor (MIF) has emerged to be an important regulator of the inflammatory response and is critically involved in the development of septic shock, arthritis, and glomerulonephritis. Although the biological activities of MIF are presumed to require a receptor-based mechanism of action, the protein is also a tautomerase and has a catalytically active N terminal proline that is invariant in structurally homologous bacterial isomerases. This observation raises the possibility that MIF may exert its biological action via an enzymatic reaction. Physiologically relevant substrates for MIF have not been identified, nor have site-directed mutagenesis studies consistently supported the requirement for a functional catalytic site. Small molecule inhibitors of MIF's isomerase activity also have been developed, but none have been shown yet to inhibit MIF biological activity. We report herein that the iminoquinone metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), inhibits both the isomerase and the biological activities of MIF. The reaction between NAPQI and MIF is covalent and produces a NAPQI-modified MIF species with diminished cell binding activity and decreased recognition by anti MIF mAb. These data are consistent with a model by which the NAPQI reacts with the catalytic Pro-1 of MIF to disrupt the integrity of epitope(s) critical to MIF's biological activity and point to the importance of the catalytic domain, but not the catalytic activity per se, in MIF function. These results also point to a powerful approach for the design of small molecule inhibitors of MIF based on interaction with its catalytic site and constitute an example of a pharmacophore capable of irreversibly inhibiting the action of a proinflammatory cytokine. PMID- 11773616 TI - A single Hox3 gene with composite bicoid and zerknullt expression characteristics in non-Cyclorrhaphan flies. AB - The members of the evolutionarily conserved Hox-gene complex, termed Hox genes, are required for specifying segmental identity during embryogenesis in various animal phyla. The Hox3 genes of winged insects have lost this ancestral function and are required for the development of extraembryonic epithelia, which do not contribute to any larval structure. Higher flies (Cyclorrhapha) such as Drosophila melanogaster contain Hox3 genes of two types, the zerknullt type and the bicoid type. The zerknullt gene is expressed zygotically on the dorsal side of the embryo and is required for establishing extraembryonic tissue. Its sister gene bicoid is expressed maternally and the transcripts are localized at the anterior pole of the mature egg. BICOID protein, which emerges from this localized source during early development, is required for embryonic patterning. All known direct bicoid homologues are confined to Cyclorrhaphan flies. Here, we describe Hox3 genes of the non-Cyclorrhaphan flies Empis livida (Empididae), Haematopota pluvialis (Tabanidae), and Clogmia albipunctata (Psychodidae). The gene sequences are more similar to zerknullt homologues than to bicoid homologues, but they share expression characteristics of both genes. We propose that an ancestral Hox3 gene had been duplicated in the stem lineage of Cyclorrhaphan flies. During evolution, one of the gene copies lost maternal expression and evolved as zerknullt, whereas the second copy lost zygotic expression and evolved as bicoid. Our finding correlates well with a partial reduction of zerknullt-dependent extraembryonic tissue during Dipteran evolution. PMID- 11773617 TI - Insect NMDA receptors mediate juvenile hormone biosynthesis. AB - In vertebrates, the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) appears to play a role in neuronal development, synaptic plasticity, memory formation, and pituitary activity. However, functional NMDAR have not yet been characterized in insects. We have now demonstrated immunohistochemically glutamatergic nerve terminals in the corpora allata of an adult female cockroach, Diploptera punctata. Cockroach corpus allatum (CA) cells, exposed to NMDA in vitro, exhibited elevated cytosolic [Ca(2+)], but not in culture medium nominally free of calcium or containing NMDAR-specific channel blockers: MK-801 and Mg(2+). Sensitivity of cockroach corpora allata to NMDA changed cyclically during the ovarian cycle. Highly active glands of 4-day-old mated females, exposed to 3 microM NMDA, produced 70% more juvenile hormone (JH) in vitro, but the relatively inactive glands of 8-day-old mated females showed little response to the agonist. The stimulatory effect of NMDA was eliminated by augmenting the culture medium with MK-801, conantokin, or high Mg(2+). Having obtained substantive evidence of functioning NMDAR in insect corpora allata, we used reverse transcription PCR to demonstrate two mRNA transcripts, DNMDAR1 and DNMDAR2, in the ring gland and brain of last-instar Drosophila melanogaster. Immunohistochemical labeling, using mouse monoclonal antibody against rat NMDAR1, showed that only one of the three types of endocrine cells in the ring gland, CA cells, expressed rat NMDAR1-like immunoreactive protein. This antibody also labeled two brain neurons in the lateral protocerebrum, one neuron per brain hemisphere. Finally, we used the same primers for DNMDAR1 to demonstrate a fragment of putative NMDA receptor in the corpora allata of Diploptera punctata. Our results suggest that the NMDAR has a role in regulating JH synthesis and that ionotropic-subtype glutamate receptors became specialized early in animal evolution. PMID- 11773618 TI - The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase. AB - Uracil phosphoribosyltransferase (UPRT) is a member of a large family of salvage and biosynthetic enzymes, the phosphoribosyltransferases, and catalyzes the transfer of ribose 5-phosphate from alpha-d-5-phosphoribosyl-1-pyrophosphate (PRPP) to the N1 nitrogen of uracil. The UPRT from the opportunistic pathogen Toxoplasma gondii represents a promising target for rational drug design, because it can create intracellular, lethal nucleotides from subversive substrates. However, the development of such compounds requires a detailed understanding of the catalytic mechanism. Toward this end we determined the crystal structure of the T. gondii UPRT bound to uracil and cPRPP, a nonhydrolyzable PRPP analogue, to 2.5-A resolution. The structure suggests that the catalytic mechanism is substrate-assisted, and a tetramer would be the more active oligomeric form of the enzyme. Subsequent biochemical studies revealed that GTP binding, which has been suggested to play a role in catalysis by other UPRTs, causes a 6-fold activation of the T. gondii enzyme and strikingly stabilizes the tetramer form. The basis for stabilization was revealed in the 2.45-A resolution structure of the UPRT-GTP complex, whereby residues from three subunits contributed to GTP binding. Thus, our studies reveal an allosteric mechanism involving nucleotide stabilization of a more active, higher order oligomer. Such regulation of UPRT could play a role in the balance of purine and pyrimidine nucleotide pools in the cell. PMID- 11773619 TI - Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. AB - Mammary anlagen are formed in the embryo as a derivative of the epidermis, a process that is controlled by Lef-1 and therefore possibly by beta-catenin. To investigate the role of beta-catenin signaling in mammary alveolar epithelium, we have stabilized endogenous beta-catenin in differentiating alveolar epithelium through the deletion of exon 3 (amino acids 5-80) of the beta-catenin gene. This task was accomplished in mice carrying a floxed beta-catenin gene and a Cre transgene under control of the mammary-specific whey acidic protein (WAP) gene promoter or the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Stabilized beta-catenin was obtained during the first pregnancy, and its presence resulted in the dedifferentiation of alveolar epithelium followed by a transdifferentiation into epidermal and pilar structures. Extensive squamous metaplasia, but no adenocarcinomas, developed upon beta-catenin activation during pregnancy and persisted throughout involution. These data demonstrate that the activation of beta-catenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures. PMID- 11773620 TI - Conformational landscape of cytochrome c folding studied by microsecond-resolved small-angle x-ray scattering. AB - To investigate protein folding dynamics in terms of compactness, we developed a continuous-flow mixing device to make small-angle x-ray scattering measurements with the time resolution of 160 micros and characterized the radius of gyration (R(g)) of two folding intermediates of cytochrome c (cyt c). The early intermediate possesses approximately 20 A of R(g), which is smaller by approximately 4 A than that of the acid-unfolded state. The R(g) of the later intermediate is approximately 18 A, which is close to that of the molten globule state. Considering the alpha-helix content (f(H)) of the intermediates, we clarified the folding pathway of cyt c on the conformational landscape defined by R(g) and f(H). Cyt c folding proceeds with a collapse around a specific region of the protein followed by a cooperative acquisition of secondary structures and compactness. PMID- 11773621 TI - The glycosynapse. AB - Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as "markers;" however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed "glycosynapse" in analogy to "immunological synapse," the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin-tetraspanin ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes. PMID- 11773622 TI - Recruitment of intron-encoded and co-opted proteins in splicing of the bI3 group I intron RNA. AB - Detectable splicing by the Saccharomyces cerevisiae mitochondrial bI3 group I intron RNA in vitro is shown to require both an intron-encoded protein, the bI3 maturase, and the nuclear-encoded protein, Mrs1. Both proteins bind independently to the bI3 RNA. The bI3 maturase binds as a monomer, whereas Mrs1 is a dimer in solution that assembles as two dimers, cooperatively, on the RNA. The active six subunit complex has a molecular mass of 420 kDa, splices with a k(cat) of 0.3 min(-1), and binds the guanosine nucleophile with an affinity comparable to other group I introns. The functional bI3 maturase domain is translated from within the RNA that encodes the intron, has evolved a high-affinity RNA-binding activity, and is a member of the LAGLIDADG family of DNA endonucleases, but appears to have lost DNA cleavage activity. Mrs1 is a divergent member of the RNase H fold superfamily of dimeric DNA junction-resolving enzymes that also appears to have lost its nuclease activity and now functions as a tetramer in RNA binding. Thus, the bI3 ribonucleoprotein is the product of a process in which a once catalytically active RNA now obligatorily requires two facilitating protein cofactors, both of which are compromised in their original functions. PMID- 11773623 TI - Functional requirement of aquaporin-5 in plasma membranes of sweat glands. AB - The distribution and function of aquaporins (AQPs) have not previously been defined in sweat glands. In this study, AQP1, AQP3, and AQP5 mRNA were demonstrated in rat paw by reverse transcription (RT)-PCR, but AQP2 and AQP4 were not. AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting. AQP1 was identified in capillary endothelial cells by immunohistochemical labeling, but not in sweat glands or epidermis. Abundant AQP3 expression was seen in basal levels of epidermis, but not in sweat glands. AQP2 and AQP4 were not observed in either skin or sweat glands. Immunohistochemical labeling revealed abundant AQP5 in secretory parts of rat and mouse sweat glands, where immunoelectron microscopy demonstrated abundant AQP5 labeling in the apical plasma membrane. AQP5 immunolabeling of human sweat glands yielded a similar pattern. To establish the role of AQP5 in sweat secretion, we tested the response of adult mice to s.c. injection of pilocarpine, as visualized by reaction of secreted amylase with iodine/starch. The number of active sweat glands was dramatically reduced in AQP5-null (-/-) mice compared with heterozygous (+/-) and wild-type (+/+) mice. We conclude that the presence of AQP5 in plasma membranes of sweat glands is essential for secretion, providing potential insight into mechanisms underlying mammalian thermoregulation, tactile sensitivity, and the pathophysiology of hyperhidrosis. PMID- 11773624 TI - Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs. AB - The stimulatory effects of growth hormone-releasing hormone (GHRH) and the antiproliferative action of GHRH antagonists have been demonstrated in various cancers, but the receptors that mediate these responses are not clearly identified. Recently, we reported that human cancer cell lines express splice variants (SVs) of the receptors for GHRH. SV1 exhibits the greatest similarity to the pituitary GHRH receptor and is most likely to be functional. To ascertain whether SV1 mediates mitogenic effects on nonpituitary tissues, we expressed SV1 in 3T3 mouse fibroblasts and studied the properties of the transfected cells. Radioligand binding assays with (125)I-labeled GHRH antagonist JV-1-42 detected high affinity (K(d) = 0.58 +/- 0.17 nM) binding sites for GHRH with a maximal binding capacity (B(max)) of 103 +/- 17.4 fmol/mg of membrane protein in 3T3 cells transfected with pcDNA3-SV1, whereas the control cells transfected with the empty vector did not show any GHRH binding. Cell proliferation studies showed that cells expressing SV1 are much more sensitive to GHRH analogs than the pcDNA3 controls. Thus, the expression of SV1 augments the stimulatory responses to GHRH(1-29)NH(2) or GHRH agonist JI-38 and inhibitory responses to GHRH antagonist JV-1-38 as compared with pcDNA3 controls. The stimulation of SV1-expressing cells by GHRH or JI-38 is followed by an increase in cAMP production, but no GH release occurs. Vasoactive intestinal peptide had no effect, and its antagonist JV-1-53 did not inhibit the proliferation of SV1-expressing cells stimulated by GHRH. Our results suggest that SV1 could mediate responses of nonpituitary cells and various tumors to GHRH and GHRH antagonists. The presence of SV1 in several human cancer cell lines provides a rationale for antitumor therapy based on the blockade of this receptor by specific GHRH antagonists. PMID- 11773625 TI - A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. AB - Pathological angiogenesis contributes directly to profound loss of vision associated with many diseases of the eye. Recent work suggests that human tyrosyl and tryptophanyl-tRNA synthetases (TrpRS) link protein synthesis to signal transduction pathways including angiogenesis. In this study, we show that a recombinant form of a COOH-terminal fragment of TrpRS is a potent antagonist of vascular endothelial growth factor-induced angiogenesis in a mouse model and of naturally occurring retinal angiogenesis in the neonatal mouse. The angiostatic activity is dose-dependent in both systems. The recombinant fragment is similar in size to one generated naturally by alternative splicing and can be produced by proteolysis of the full-length protein. In contrast, the full-length protein is inactive as an antagonist of angiogenesis. These results suggest that fragments of TrpRS, as naturally occurring and potentially nonimmunogenic anti-angiogenics, can be used for the treatment of neovascular eye diseases. PMID- 11773626 TI - A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. AB - Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis. It was shown recently that human tyrosyl-tRNA synthetase (TyrRS) can be split into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase (TrpRS) is a close homologue of TyrRS. A natural fragment, herein designated as mini TrpRS, was shown by others to be produced by alternative splicing. Production of this fragment is reported to be stimulated by IFN-gamma, a cytokine that also stimulates production of angiostatic factors. Mini TrpRS is shown here to be angiostatic in a mammalian cell culture system, the chicken embryo, and two independent angiogenesis assays in the mouse. The full-length enzyme is inactive in the same assays. Thus, protein synthesis may be linked to the regulation of angiogenesis by a natural fragment of TrpRS. PMID- 11773627 TI - Directed molecular evolution of ADP-glucose pyrophosphorylase. AB - ADP-glucose pyrophosphorylase catalyzes a rate-limiting reaction in prokaryotic glycogen and plant starch biosynthesis. Despite sharing similar molecular size and catalytic and allosteric regulatory properties, the prokaryotic and higher plant enzymes differ in higher-order protein structure. The bacterial enzyme is encoded by a single gene whose product of ca. 50,000 Da assembles into a homotetrameric structure. Although the higher plant enzyme has a similar molecular size, it is made up of a pair of large subunits and a pair of small subunits, encoded by different genes. To identify the basis for the evolution of AGPase function and quaternary structure, a potato small subunit homotetrameric mutant, TG-15, was subjected to iterations of DNA shuffling and screened for enzyme variants with up-regulated catalytic and/or regulatory properties. A glycogen selection/screening regimen of buoyant density gradient centrifugation and iodine vapor colony staining on glucose-containing media was used to increase the stringency of selection. This approach led to the isolation of a population of AGPase small subunit homotetramer enzymes with enhanced affinity toward ATP and increased sensitivity to activator and/or greater resistance to inhibition than TG-15. Several enzymes displayed a shift in effector preference from 3 phosphoglycerate to fructose-6 phosphate or fructose-1,6-bis-phosphate, effectors used by specific bacterial AGPases. Our results suggest that evolution of AGPase, with regard to quaternary structure, allosteric effector selectivity, and effector sensitivity, can occur through the introduction of a few point mutations alone with low-level recombination hastening the process. PMID- 11773628 TI - Temporal binding via cortical coincidence detection of specific and nonspecific thalamocortical inputs: a voltage-dependent dye-imaging study in mouse brain slices. AB - Voltage-sensitive dye imaging of mouse thalamocortical slices demonstrated that electrical stimulation of the centrolateral intralaminar thalamic nucleus (CL) resulted in the specific activation of thalamic reticular nucleus, striatum/putamen, and cortical layers 5, 6, and 1. By contrast, ventrobasal (VB) thalamic stimulation, while activating the reticular and basal ganglia nuclei, also activated directly layers 4 and deep 5 of the cortex. Conjoined stimulation of the VB and CL nuclei resulted in supralinear summation of the two inputs at cortical output layer 5, demonstrating coincidence detection along the apical dendrites. This supralinear summation was also noticed at gamma band stimulus frequency ( approximately 40 Hz). Direct stimulation of cortical layer 1, after a radial section of the cortex that spared only that layer, was shown to sum supralinearly with the cortical activation triggered by VB stimulation, providing a second demonstration for coincidence detection. Coincidence detection by coactivation of the specific (VB) and nonspecific (CL) thalamic nuclei has been proposed as the basis for the temporal conjunction that supports cognitive binding in the brain. PMID- 11773629 TI - Brain signatures of artificial language processing: evidence challenging the critical period hypothesis. AB - Adult second language learning seems to be more difficult and less efficient than first language acquisition during childhood. By using event-related brain potentials, we show that adults who learned a miniature artificial language display a similar real-time pattern of brain activation when processing this language as native speakers do when processing natural languages. Participants trained in the artificial language showed two event-related brain potential components taken to reflect early automatic and late controlled syntactic processes, whereas untrained participants did not. This result challenges the common view that late second language learners process language in a principally different way from native speakers. Our findings demonstrate that a small system of grammatical rules can be syntactically instantiated by the adult speaker in a way that strongly resembles native-speaker sentence processing. PMID- 11773630 TI - Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. AB - Infection of the mouse trigeminal ganglia (TG) is the most commonly used model for the study of herpes simplex virus type 1 (HSV-1) latency. Its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. However, this perception has never been rigorously tested. To carefully study this issue, the eyes of Swiss-Webster mice were inoculated with HSV-1 (KOS), and 37-47 days later the TG were dissected, serial-sectioned, and probed for HSV-1 ICP4, thymidine kinase, glycoprotein C, and latency-associated transcript RNA by in situ hybridization. Serial sections of additional latently infected TG were probed with HSV-1-specific polyclonal antisera. Analysis of thousands of probed sections revealed abundant expression of viral transcripts, viral protein, and viral DNA replication in about 1 neuron per 10 TG tested. These same neurons were surrounded by a focal white cell infiltrate, indicating the presence of an antigenic stimulus. We conclude that productive cycle viral genes are abundantly expressed in rare neurons of latently infected murine TG and that these events are promptly recognized by an active local immune response. In the absence of detectable infectious virus in these ganglia, we propose the term "spontaneous molecular reactivation" to describe this ongoing process. PMID- 11773631 TI - Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum variant patients. AB - Xeroderma pigmentosum variant (XP-V) cells are deficient in their ability to synthesize intact daughter DNA strands after UV irradiation. This deficiency results from mutations in the gene encoding DNA polymerase eta, which is required for effecting translesion synthesis (TLS) past UV photoproducts. We have developed a simple cellular procedure to identify XP-V cell strains, and have subsequently analyzed the mutations in 21 patients with XP-V. The 16 mutations that we have identified fall into three categories. Many of them result in severe truncations of the protein and are effectively null alleles. However, we have also identified five missense mutations located in the conserved catalytic domain of the protein. Extracts of cells falling into these two categories are defective in the ability to carry out TLS past sites of DNA damage. Three mutations cause truncations at the C terminus such that the catalytic domains are intact, and extracts from these cells are able to carry out TLS. From our previous work, however, we anticipate that protein in these cells will not be localized in the nucleus nor will it be relocalized into replication foci during DNA replication. The spectrum of both missense and truncating mutations is markedly skewed toward the N-terminal half of the protein. Two of the missense mutations are predicted to affect the interaction with DNA, the others are likely to disrupt the three dimensional structure of the protein. There is a wide variability in clinical features among patients, which is not obviously related to the site or type of mutation. PMID- 11773632 TI - Snapshot of a key intermediate in enzymatic thiamin catalysis: crystal structure of the alpha-carbanion of (alpha,beta-dihydroxyethyl)-thiamin diphosphate in the active site of transketolase from Saccharomyces cerevisiae. AB - Kinetic and spectroscopic data indicated that addition of the donor substrate hydroxypyruvate to the thiamin diphosphate (ThDP)-dependent enzyme transketolase (TK) led to the accumulation of the alpha-carbanion/enamine of (alpha,beta dihydroxyethyl) ThDP, the key reaction intermediate in enzymatic thiamin catalysis. The three-dimensional structure of this intermediate trapped in the active site of yeast TK was determined to 1.9-A resolution by using cryocrystallography. The electron density suggests a planar alpha carbanion/enamine intermediate having the E-configuration. The reaction intermediate is firmly held in place through direct hydrogen bonds to His-103 and His-481 and an indirect hydrogen bond via a water molecule to His-69. The 4-NH(2) group of the amino-pyrimidine ring of ThDP is within 3 A distance to the alpha hydroxy oxygen atom of the dihydroxyethyl moiety but at an angle unfavorable for a strong hydrogen bond. No structural changes occur in TK on formation of the reaction intermediate, suggesting that the active site is poised for catalysis and conformational changes during the enzyme reaction are not very likely. The intermediate is present with high occupancy in both active sites, arguing against previous proposals of half-of-the-sites reactivity in yeast TK. PMID- 11773633 TI - The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration. AB - Normal human retinal development involves orderly generation of rods and cones by complex mechanisms. Cell-fate specification involves progenitor cell lineage and external signals such as soluble factors and cell-cell interactions. In most inherited human retinal degenerations, including retinitis pigmentosa, a mutant gene causes loss of visual function, death of mature rods, and eventually death of all cone subtypes. Only one inherited retinal disorder, the enhanced S cone syndrome (ESCS), shows increased visual function, involving the minority S (blue) cones, and decreased rod and L/M (red/green) cone function. This autosomal recessive disease is caused by mutations in NR2E3, a photoreceptor nuclear receptor transcription factor, and may result from abnormal cell-fate determination, leading to excess S cones at the expense of other photoreceptor subtypes. In 16 ESCS patients with the most common NR2E3 mutation, R311Q, we documented an abnormal ratio of S to L/M cone function and progressive retinal degeneration. We studied the postmortem retina of an ESCS patient homozygous for NR2E3 R311Q. No rods were identified, but cones were increased approximately 2 fold, and 92% were S cones. Only 15% of the cones expressed L/M cone opsin, and some coexpressed S cone opsin. The retina was disorganized, with densely packed cones intermixed with inner retinal neurons. The retina was also degenerate, retaining photoreceptors in only the central and far peripheral regions. These observations suggest a key role for NR2E3 in regulation of human photoreceptor development. Degeneration of the NR2E3 retina may result from defective development, known S cone fragility, or abnormal maintenance of mature photoreceptors. PMID- 11773634 TI - Decreased pulmonary vascular permeability in aquaporin-1-null humans. AB - The molecular determinants of water permeability in the human lung are incompletely defined. Aquaporins (AQP) are water-specific membrane channel proteins. AQP1 is present in endothelial cells in the lung, including those in the vascular plexus around the airways. Rare individuals have been identified who are deficient in AQP1. High-resolution computed tomography scans of the lung were used to evaluate the response to i.v. fluid challenge in two unrelated AQP1-null individuals and five normal controls. The airways and pulmonary vessels were measured at baseline and after i.v. administration of 3 liters of saline. Increases in airway wall thickness after fluid administration reflect peribronchiolar edema formation. Both control and AQP1 null subjects had approximately a 20% increase in pulmonary vessel area in response to saline infusion, suggesting similar degrees of volume loading. Control subjects had a 44% increase in the thickness of the airway wall, consistent with peribronchiolar edema formation. In marked contrast, airway wall thickness did not change in AQP1 null subjects in response to saline infusion. These studies indicate that AQP1 is a determinant of vascular permeability in the lung, and demonstrate a role for aquaporins in human pulmonary physiology. PMID- 11773635 TI - Ca(2+)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. AB - A deletion mutation Delta K210 in cardiac troponin T (cTnT) was recently found to cause familial dilated cardiomyopathy (DCM). To explore the effect of this mutation on cardiac muscle contraction under physiological conditions, we determined the Ca(2+)-activated force generation in permeabilized rabbit cardiac muscle fibers into which the mutant and wild-type cTnTs were incorporated by using our TnT exchange technique. The free Ca(2+) concentrations required for the force generation were higher in the mutant cTnT-exchanged fibers than in the wild type cTnT-exchanged ones, with no statistically significant differences in maximal force-generating capability and cooperativity. Exchanging the mutant cTnT into isolated cardiac myofibrils also increased the free Ca(2+) concentrations required for the activation of ATPase. In contrast, a deletion mutation Delta E160 in cTnT that causes familial hypertrophic cardiomyopathy (HCM) decreased the free Ca(2+) concentrations required for force generation, just as in the case of the other HCM-causing mutations in cTnT. The results indicate that cTnT mutations found in the two distinct forms of cardiomyopathy (i.e., HCM and DCM) change the Ca(2+) sensitivity of cardiac muscle contraction in opposite directions. The present study strongly suggests that Ca(2+) desensitization of force generation in sarcomere is a primary mechanism for the pathogenesis of DCM associated with the deletion mutation Delta K210 in cTnT. PMID- 11773637 TI - A closer look at the elementary fermions. AB - Although there have been many experimental and theoretical efforts to measure and interpret small deviations from the standard model of particle physics, the gap that the model leaves in understanding why there are only three generations of the elementary fermions, with hierarchical masses, has not received the attention it deserves. I present here an attempt to fill this gap. Although our findings are mostly only qualitative, they nevertheless may be of heuristic value. Rules concerning the elementary fermions, some previously known and some new, lead to a number of conclusions and questions that seem worth pursuing. Some clarify the standard model, and others suggest possible modifications, the implications of which are discussed. PMID- 11773636 TI - Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes. AB - Trichromacy in humans and other Old World primates evolved from a dichromatic color vision system approximately 30-40 million years ago. One essential part of this evolution was the duplication and divergence of sequences on the X chromosome to create the present-day red and green cone pigment genes. Earlier work demonstrated that a locus control region (LCR) located upstream of these genes is essential for their expression. In the present work, we have generated a variety of modified human red and green pigment gene arrays that direct the expression of distinguishable histochemical reporters from each gene promoter. Transgenic mice carrying a single copy of each modified array were studied to define the role of three variables in producing mutually exclusive expression of red and green pigment transgenes: the distance between the promoter and the LCR, the identity of the visual pigment promoter, and LCR copy number. The results support a model in which the mutually exclusive expression of these genes in their respective cone types is controlled by competition between visual pigment promoters for pairing with the LCR, and they suggest a facile mechanism for the evolution of trichromacy after visual pigment gene duplication. PMID- 11773638 TI - Mullerian-inhibiting substance regulates NF-kappa B signaling in the prostate in vitro and in vivo. AB - Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor beta superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes restricted to the most caudal ends that fuse to form the prostatic utricle. In this article, we have demonstrated MIS type II receptor expression in the normal prostate, human prostate cancer cell lines, and tissue derived from patients with prostate adenocarcinomas. MIS induced NF-kappaB DNA binding activity and selectively up-regulated the immediate early gene IEX-1S in both androgen-dependent and independent human prostate cancer cells in vitro. Dominant negative IkappaBalpha expression ablated both MIS-induced increase of IEX-1S mRNA and inhibition of growth, indicating that activation of NF-kappaB signaling was required for these processes. Androgen also induced NF-kappaB DNA binding activity in prostate cancer cells but without induction of IEX-1S mRNA, suggesting that MIS-mediated increase in IEX-1S was independent of androgen mediated signaling. Administration of MIS to male mice induced IEX-1S mRNA in the prostate in vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF-kappaB signaling and growth in the prostate gland. PMID- 11773640 TI - Clinical parity in emergency mental health. PMID- 11773642 TI - Datapoints: payer source for emergency room visits by persons with psychiatric disorders. PMID- 11773643 TI - Rehab rounds: training professionals in use of positive methods for community integration of persons with developmental disabilities. AB - Mainstream psychiatry has all but ignored the clinical needs of persons with developmental disabilities. With some notable exceptions, individuals in this group have been served in the community by behaviorally oriented psychologists or relegated to long-term institutional care. However, effective interventions are available, beginning with a functional analysis of the antecedents and consequences of targeted problem behaviors. Procedures for building adaptive coping and functional skills or compensating for their deficiency have been developed that are based on skills training, wraparound supports for employment and community living, stimulus control, and contingencies of reinforcement. Applied behavior analysis using task analysis, stimulus control, and contingencies of reinforcement also spawned some of the first techniques- including the token economy--shown to improve functioning and reduce psychopathology among persons with schizophrenia. One of the premier organizations to have documented the efficacy of person-centered, behavior analytic, and community-based wraparound support services for persons with developmental disabilities is the Institute for Applied Behavior Analysis in Los Angeles. The institute was founded 20 years ago and has served more than 1,000 children, adolescents, and adults with developmental disabilities. Its staff have designed and empirically validated nonaversive techniques for modifying the behaviors that place their clients or others at risk of harm or injury and that often lead to the clients' ejection or isolation from community life. In this Rehab Rounds column the authors describe and evaluate the institute's training and consultation activities. PMID- 11773644 TI - Coping with grief. PMID- 11773645 TI - Managed care: strengthening the consumer voice in managed care: III. The Philadelphia Consumer Satisfaction Team. PMID- 11773639 TI - Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. AB - The immune system generally avoids horror autotoxicus or autoimmunity, an attack against the body's own constituents. This avoidance requires that self-reactive T cells be actively silenced or tolerized. We propose that dendritic cells (DCs) play a critical role in establishing tolerance, especially in the periphery, after functioning T cells have been produced in the thymus. In the steady state, meaning in the absence of acute infection and inflammation, DCs are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. Nevertheless, immature DCs continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature DCs silence T cells either by deleting them or by expanding regulatory T cells. This capacity of DCs to induce peripheral tolerance can work in two opposing ways in the context of infection. In acute infection, a beneficial effect should occur. The immune system would overcome the risk of developing autoimmunity and chronic inflammation if, before infection, tolerance were induced to innocuous environmental proteins as well as self antigens captured from dying infected cells. For chronic or persistent pathogens, a second but dire potential could take place. Continuous presentation of a pathogen by immature DCs, HIV-1 for example, may lead to tolerance and active evasion of protective immunity. The function of DCs in defining immunologic self provides a new focus for the study of autoimmunity and chronic immune-based diseases. PMID- 11773646 TI - Law & psychiatry: Can a psychiatrist be held responsible when a patient commits murder? PMID- 11773647 TI - Highlights of the 2001 Institute on Psychiatric Services. PMID- 11773648 TI - Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. AB - OBJECTIVE: Despite the widespread use of benzodiazepines during pregnancy and lactation, little information is available about their effect on the developing fetus and on nursing infants. The authors review what is currently known about the effects of benzodiazepine therapy on the fetus and on nursing infants. METHODS: A MEDLINE search of the literature between 1966 and 2000 was conducted with the terms "benzodiazepines," "diazepam," "chlordiazepoxide," "clonazepam," "lorazepam," "alprazolam," "pregnancy," "lactation," "fetus," and "neonates." RESULTS: Currently available information is insufficient to determine whether the potential benefits of benzodiazepines to the mother outweigh the risks to the fetus. The therapeutic value of a given drug must be weighed against theoretical adverse effects on the fetus before and after birth. The available literature suggests that it is safe to take diazepam during pregnancy but not during lactation because it can cause lethargy, sedation, and weight loss in infants. The use of chlordiazepoxide during pregnancy and lactation seems to be safe. Avoidance of alprazolam during pregnancy and lactation would be prudent. To avoid the potential risk of congenital defects, physicians should use the benzodiazepines that have long safety records and should prescribe a benzodiazepine as monotherapy at the lowest effective dosage for the shortest possible duration. High peak concentrations should be avoided by dividing the daily dosage into two or three doses. CONCLUSIONS: Minimizing the risks of benzodiazepine therapy among pregnant or lactating women involves using drugs that have established safety records at the lowest dosage for the shortest possible duration, avoiding use during the first trimester, and avoiding multidrug regimens. PMID- 11773649 TI - Predicting incarceration of clients of a psychiatric probation and parole service. AB - OBJECTIVE: This study assessed the extent to which clinical characteristics, psychiatric status, and use of mental health services explain incarceration for technical violations of probation or parole rather than incarceration for new offenses. METHODS: A total of 250 clients of an urban psychiatric probation and parole service were screened for psychiatric diagnoses and monitored with a 12 month data collection protocol. Longitudinal analysis was used to explain incarceration on new charges, incarceration on technical violations of probation and parole, or absence of incarceration. RESULTS: Eighty-five individuals (34 percent) were incarcerated during the follow-up period. Forty-four (18 percent) were incarcerated for a new offense, and 41 (16 percent) were incarcerated for a technical violation. Participation in mental health treatment was associated with a lower risk of incarceration for a technical violation. Intensive monitoring by mental health providers, such as through case management and medication management, were significant risk factors for incarceration for a technical violation. Clients who were incarcerated for a technical violation were more than six times as likely to have received intensive case management services. CONCLUSIONS: The role of mental health services in reducing the risk of incarceration remains mixed. Providing services that emphasize monitoring tends to increase the risk of incarceration for technical violations of criminal justice sanctions. However, any participation in treatment and motivation to participate in treatment appears to reduce the risk of incarceration. PMID- 11773650 TI - Severity of children's psychopathology and impairment and its relationship to treatment setting. AB - OBJECTIVE: The study investigated the settings in which children and adolescents were treated to determine whether clinicians assigned individuals who had greater needs to more intensive treatment. METHODS: Subjects were 603 children four to 16 years of age who visited a mental health treatment facility in Western Australia, where, as is the case throughout Australia, universal publicly funded health care is provided. DSM-IV criteria were used to make diagnoses, and clinicians assessed each child's level of impairment. The clinicians assigned the children to inpatient treatment, day treatment, or outpatient treatment, or they saw the child only for a psychiatric consultation. Measures included parents' and children's reports of children's psychopathology and parents' reports of family functioning, family life events, and parental mental health symptoms and treatment. RESULTS: Clinicians' ratings of impairment were highest for children assigned to the inpatient and day treatment settings. Parents' ratings of total psychopathology and of internalizing and externalizing symptoms were highest for children in the inpatient and day treatment settings. Parents' reports also indicated that family dysfunction and parental alcohol problems were most severe in the inpatient group. No differences in parents' mental health problems were found across treatment settings. CONCLUSIONS: Children with more severe psychopathology and more severe family dysfunction and parental problems were more likely to be provided treatment in the most costly and time-intensive treatment settings. The results provide empirical evidence for what many clinicians consider best clinical practice-to assign children and families to treatment settings appropriate to their level of impairment. PMID- 11773651 TI - Work rehabilitation and patterns of substance use among persons with schizophrenia. AB - OBJECTIVE: The aim of this study was to identify patterns of substance use among participants in work rehabilitation, to identify symptom patterns associated with substance use, and to assess the impact of substance use on work rehabilitation outcomes. METHODS: Addiction Severity Index interviews were conducted and Positive and Negative Syndrome Scale ratings were obtained at the start of the study and again five months and 12 months later for 220 patients with schizophrenia or schizoaffective disorder who were already enrolled in a study of work rehabilitation. RESULTS: Eighty percent of the participants met Addiction Severity Index criteria for lifetime substance use, but 75 percent were abstinent at intake. During the 12-month follow-up period, abstinence rates remained above 66 percent. Participants with a lifetime history of cocaine use were more likely to return to substance use. The type of substance used was also related to distinct symptom patterns. Participants with past cocaine use had more severe hostility symptoms and less severe negative symptoms. No significant relationships were found between lifetime or current substance use and participation in the work rehabilitation program. CONCLUSIONS: Even though a high rate of lifetime substance use was observed in this sample, most participants were in stable remission of substance use throughout the one-year study. Substance use and work participation appeared to be semiautonomous: substance use did not directly affect work participation, and work participation did not directly affect substance use. PMID- 11773652 TI - Gender differences in juvenile arrestees' drug use, self-reported dependence, and perceived need for treatment. AB - OBJECTIVES: The authors examined gender differences in drug use, self-reported dependence, and perceived need for treatment in a national sample of juvenile arrestees and detainees between the ages of nine and 18 years. METHODS: A sample of 4,644 boys and girls, drawn from the Juvenile Drug Use Forecasting Survey from 1992 to 1995, was matched by sex within each of seven sites by survey year. In anonymous interviews, respondents were asked about their living arrangements, drug use, and need for drug treatment. Questions about drug use covered marijuana, cocaine, crack, heroin, crystal methamphetamine, amphetamines, and phencyclidine (PCP). Logistic regression was used to identify significant predictors of drug dependence and perceived need for treatment. RESULTS: Girls were significantly more likely than boys to report dependence but were no more likely to report a need for treatment. Among those who reported current, frequent drug use, girls were significantly less likely than boys to report a need for treatment. Girls who reported having more severe drug problems were more likely than their male counterparts to report dependence and a need for treatment. CONCLUSIONS: The ways in which juvenile arrestees report drug dependence and need for treatment differ by gender. Clinicians should assess and reduce barriers to treatment perceived by girls in particular to engage them in services before their drug use escalates. PMID- 11773653 TI - The association between decreasing length of stay and readmission rate on a psychogeriatric unit. AB - OBJECTIVE: This study investigated whether there was an association between decreasing length of stay and readmission rate on a psychogeriatric unit. METHODS: Discharge summaries were reviewed for all 1,099 admissions to a university hospital psychogeriatric unit from January 1993 through December 1997. Data were collected for all 77 patients who were readmitted within 30 days of a previous discharge and for an equal number of randomly selected patients who were not readmitted. Data included length of stay, diagnosis, disposition, and demographic information. RESULTS: Mean length of stay decreased significantly over the five-year study period for patients who were readmitted and for those who were not readmitted. The mean length of stay for the index admission of readmitted patients decreased from 33.6 days to 9.5 days. The mean length of stay of patients who were not readmitted decreased from 27.5 days to 12.7 days. Over the same period, the readmission rate doubled, rising from 5.3 percent (seven patients) to 10.8 percent (30 patients), and the proportion of patients who were discharged to the geriatric day hospital increased significantly. CONCLUSIONS: Although it is difficult to demonstrate causality, these findings indicate a temporal association between decreasing length of stay and rate of readmission to a university hospital psychogeriatric unit. PMID- 11773654 TI - Prevalence and severity of mental health-related disability and relationship to diagnosis. AB - OBJECTIVE: Psychiatric disability has been defined largely from measures that focus on serious mental illness. This practice may have led to substantial underestimation of the total impact of mental disorders on community health. In this study a generic measure of mental health-related disability was used to examine disabilities attributable to various common mental disorders. METHODS: Data were drawn from the Australian National Survey of Mental Health and Wellbeing, a household survey of 10,641 adults that assessed participants for 14 DSM-IV disorders with use of the Composite International Diagnostic Interview. Screening instruments were used to identify likely cases of ICD-10 personality disorder, neurasthenia (an undifferentiated somatoform disorder), and psychosis. Mental health disability was assessed with the Medical Outcomes Study 12-item Short Form (SF-12) mental health summary scale, which was administered to all participants. RESULTS: Disability was significantly greater among participants with a current psychiatric diagnosis, and disability varied by type of disorder. Diagnosis remained a strong predictor of disability after sociodemographic factors and physical illness were controlled for. Disorders found to be independently associated with disability were depression, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, alcohol dependence, and drug dependence. CONCLUSIONS: Substantial proportions of persons with mental disorders that are not usually classified as major mental disorders reported moderate and severe disability. A generic measure of mental health-related disability was able to detect variations in disability among persons with different diagnoses. Although such a measure is not as sensitive as a disorder specific measure developed for use in psychiatric populations, it can facilitate comparison of disability across common mental disorders. PMID- 11773655 TI - Patients' and staff members' attitudes about the rights of hospitalized psychiatric patients. AB - OBJECTIVE: The goal of this study was to assess and compare patients' and staff members' attitudes about what rights hospitalized psychiatric patients should have. METHODS: A 31-item inventory, developed for the study, for assessing attitudes about what rights hospitalized psychiatric patients should have was used with 122 hospitalized psychiatric patients and 35 staff members in the same hospital. RESULTS: Patients were less likely than staff to express the view that involuntary hospitalization, the use of force or physical restrictions, or the compromise of confidentiality is justified. There were no significant differences in attitudes toward patients' rights to obtain information about their illness and treatment and their right to refuse treatment. CONCLUSIONS: The differences in attitudes found in the study highlight the importance of considering multiple facets of patients' rights and the extent to which attitudes about patients' rights are associated with each facet. PMID- 11773656 TI - Seven-year outcomes of patients evaluated for suicidality. AB - This study assessed the seven-year outcomes of 137 patients who presented with suicidality. Forty-five of the patients were contingently suicidal, that is, they originally presented with suicidal threats designed to gain hospital admission; 92 patients were noncontingently suicidal. Administrative and clinical records were examined for adverse outcomes, and suspicious cases were further investigated. Significant differences were found between the groups in overall mortality and serious suicide attempts. Although no suicides were identified in the contingently suicidal group, ten suicides were confirmed or highly suspected among the noncontingently suicidal patients. This group also had higher overall death rates. These results argue for evaluation of contingency in suicide risk assessments. PMID- 11773657 TI - Pharmacologic treatment of hospitalized patients with schizoaffective disorder. AB - This study examined changes in the pharmacologic treatment of 70 patients who were hospitalized with a diagnosis of schizoaffective disorder at some time during a six-year period. An increasing use of divalproex sodium and atypical antipsychotics instead of lithium and conventional antipsychotics was observed. The use of a combination of an antipsychotic and a thymoleptic medication was more common than monotherapy, and physicians tended to continue antidepressants if patients had a history of depression. Patients with a new diagnosis of schizoaffective disorder were stabilized less quickly than those with a previous diagnosis. The use of divalproex sodium and newer antipsychotics did not reduce the time to stabilization in routine clinical practice. PMID- 11773658 TI - Factors associated with insight among outpatients with serious mental illness. AB - This study examined the relationships between insight, severity of symptoms, diagnosis, locus of control, quality of life, and engulfment among 25 patients with a DSM-III-R diagnosis of schizophrenia and 33 patients with a diagnosis of bipolar disorder. Engulfment is the extent to which a person identifies with the patient role. Severity of symptoms and engulfment were significantly associated with insight. These results are consistent with the notion that poor insight is associated with severe illness. The association between development of deviant or sick roles and awareness of illness warrants further attention. PMID- 11773659 TI - Harlem Hospital Center's geropsychiatric service. PMID- 11773660 TI - Computer-facilitated dialogue with patients who have schizophrenia. PMID- 11773661 TI - Closure of state psychiatric hospitals for children. PMID- 11773663 TI - Treatment of ADHD when tolerance to methylphenidate develops. PMID- 11773664 TI - Effectiveness of assertive community treatment. PMID- 11773665 TI - Evidence-based alternative medicine. PMID- 11773666 TI - Epidemiology and detection of human immunodeficiency virus among pregnant women in Hong Kong. AB - OBJECTIVES: To determine the epidemiology of human immunodeficiency virus infection among pregnant women and the neonatal outcomes in Hong Kong. DESIGN: Retrospective observational study composed of two parts: record review of pregnant women and unlinked anonymous screening of cord blood from neonates. SETTING: Two human immunodeficiency virus clinics and the Government Virus Unit. PARTICIPANTS: Female patients attending the two clinics who became pregnant and neonates who underwent routine metabolic screening by the Government Virus Unit between 1992 and 1999. MAIN OUTCOME MEASURES: The outcomes of neonates born to women who had human immunodeficiency virus infection during pregnancy. RESULTS: Forty-one human immunodeficiency virus-related pregnancies were recorded among 32 infected women. Fifteen pregnancies were terminated, of which 14 were in women who knew their infection status before conception. Twenty-six pregnancies continued to term, resulting in 26 live births. Twelve babies were born to women who knew their infection status before delivery. One baby was confirmed to be infected. Six women were given zidovudine for prophylaxis against vertical transmission and none of the babies were infected at birth. Of the remaining 14 human immunodeficiency virus-related pregnancies, the mothers' status became known only at a later date and nine (64.3%) babies were confirmed to be infected at the age of 18 months or older. The rate ratio of giving birth to an infected baby was 8.18 from mothers who did not know their status antenatally. Unlinked anonymous screening showed that the seroprevalence rate for human immunodeficiency virus in pregnant women was 0.032% (1/3125) in Hong Kong in 1999. CONCLUSIONS: Human immunodeficiency virus-related pregnancy is not rare in Hong Kong and the majority of infected mothers were not identified and treated. Detection of these pregnancies will be invaluable for the prevention of mother-to child transmission. Universal antenatal screening of human immunodeficiency virus antibody is proposed as an effective strategy. PMID- 11773667 TI - Characteristics of workers attending the pneumoconiosis clinic for silicosis assessment in Hong Kong: retrospective study. AB - OBJECTIVE: To describe and analyse the baseline characteristics of workers attending the pneumoconiosis clinic for assessment of silicosis. DESIGN: Retrospective cross-sectional study. SETTING: Outpatient clinic. PATIENTS: One thousand and fifty-six patients with silica dust exposure attending the pneumoconiosis clinic for compensation assessment. MAIN OUTCOME MEASURES: Baseline demographic characteristics, lung function parameters, and radiographic findings. RESULTS: Six hundred and forty-eight patients were diagnosed with silicosis, of which 10 were female. Excluding the data on female patients, the mean duration of dust exposure was 24.2 years. The majority of patients were involved in caisson work and stone splitting. Most newly diagnosed patients had simple silicosis. Less than a quarter (24.8%) had progressive massive fibrosis. Lung function parameters at diagnosis were within the normal range. Pulmonary tuberculosis remained an important co-existing disease. CONCLUSION: The major cause of silicosis in Hong Kong is chronic silica dust exposure in the construction industry. Simple silicosis predominated at diagnosis, with normal lung function parameters seen in the majority of patients. PMID- 11773668 TI - Diabetic foot ulcers in the Hong Kong Chinese population: retrospective study. AB - OBJECTIVE: To assess the predictive power of various parameters on the final outcome of ulcerated diabetic feet among the Hong Kong Chinese population. DESIGN: Retrospective cohort study. SETTING: Regional public hospital, Hong Kong. PATIENTS: Medical records of 340 diabetic patients with foot ulcers (535) who were referred to the Diabetic Foot Clinic between July 1995 and June 2000 were reviewed. MAIN OUTCOME MEASURES: Demographic and clinical data, including assessment of the foot and blood parameters. RESULTS: Increasing age, wound depth, the presence of ischaemia, a low albumin level, and the lack of simultaneous ulceration were determined by stepwise logistic regression analysis to be the most significant independent predictors of an unfavourable outcome. CONCLUSIONS: Major amputation is more likely to occur in elderly patients, with progressive wound depth, and in the presence of ischaemia. A low albumin level was also noted to be an independent predictor of major amputation in the population studied. PMID- 11773669 TI - Clinical efficacy of proton pump inhibitor therapy in neurologically impaired children with gastroesophageal reflux: prospective study. AB - OBJECTIVE: To study the effects of proton pump inhibitors in reducing vomiting, gastrointestinal bleeding, and chest infections in institutionalised neurologically impaired children with gastroesophageal reflux. DESIGN: Prospective study. SETTING: A regional hospital, Hong Kong. PATIENTS: Neurologically impaired children with refractory gastroesophageal reflux. MAIN OUTCOME MEASURES: Episodes of vomiting, gastrointestinal bleeding, and pneumonia in the baseline and proton pump inhibitor treatment periods. RESULTS: Nine children received proton pump inhibitor therapy for a median duration of 81 days. Mean reflux index was 9.3% (standard deviation, 5%). Dosage of omeprazole used was 1.0-2.3 mg/kg/d. Vomiting was reduced significantly with proton pump inhibitor treatment (median vomiting index [baseline]=0.4, median vomiting index [proton pump inhibitors]=0.2; P<0.05). No significant decrease in gastrointestinal bleeding or chest infection was observed. CONCLUSION: Proton pump inhibitors significantly reduced vomiting episodes in neurologically impaired children with gastroesophageal reflux. PMID- 11773670 TI - Cost-effectiveness analysis of applying the Cholesterol and Recurrent Events (CARE) study protocol in Hong Kong. AB - OBJECTIVE: To determine the cost-effectiveness of secondary prevention with pravastatin in Hong Kong patients with coronary heart disease and average cholesterol levels. DESIGN: Cost-effectiveness analysis based on published results of the CARE study. PATIENTS: Men and women post-myocardial infarction with average cholesterol levels. MAIN OUTCOME MEASURES: Cost-effectiveness analysis: cost per life saved, cost per fatal or non-fatal coronary event prevented, cost per procedure prevented, and cost per fatal or non-fatal stroke prevented. Cost-utility analysis: gross cost and net cost per quality-adjusted life year gained calculated using two alternative models. RESULTS: Cost per life saved or death prevented was HK$4,442,350 (non-discounted); cost per fatal or non fatal cardiac event prevented HK$1,146,413; cost per procedure prevented HK$732,759; and cost per fatal or non-fatal stroke prevented HK$2,961,566. Net cost per quality adjusted life year gained was HK$73,218 and HK$65,280 non discounted, respectively using the two alternative models. CONCLUSIONS: The results of this study can assist in prioritising the use of health care resources in Hong Kong but should be considered alongside the benefits and costs of alternative interventions for coronary heart disease. PMID- 11773671 TI - The medicinal action of androgens and green tea epigallocatechin gallate. AB - Unorthodox (non-traditional or alternative) medicinal practices have been expanding very rapidly in western countries. Modern physicians, scientists, and non-traditional medicine practitioners now must join forces to promote evidence based medicine to benefit patients. Green tea extracts are among the most widely used ancient medicinal agents, while androgens are probably the oldest drugs used in a purified form in traditional Chinese medicine. It is now clear that a specific green tea catechin, (-)epigallocatechin-3-gallate, can modulate the production and biological actions of androgens and other hormones. Modulation of androgenic activity and administration of (-)epigallocatechin-3-gallate may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, baldness, and acne, as well as androgen-dependent and independent prostate cancers. (-)Epigallocatechin-3-gallate has also been shown to modulate appetite and control obesity in animals. PMID- 11773672 TI - An efficacy-driven approach to the research and development of traditional Chinese medicine. AB - Research activities in traditional Chinese medicine have, to date, focused on the search for relevant active substances and mechanisms of action. This research approach is shaped partly by the conventional drug development model, which commences with determining the mechanism of disease, followed by the design and synthesis of therapeutically active compounds or molecules, animal and in vitro studies, and finally clinical trials in humans. Demonstration of clinical efficacy in humans using randomised controlled trials may be a better starting point for research into traditional Chinese medicine, given that these therapies are already in common use. An efficacy-driven approach could avoid basic research into therapies that are clinically ineffective, thus sparing precious research resources. PMID- 11773673 TI - Acupuncture for frozen shoulder. AB - This randomised controlled trial was undertaken to evaluate the effectiveness of acupuncture as a treatment for frozen shoulder. Thirty-five patients with a diagnosis of frozen shoulder were randomly allocated to an exercise group or an exercise plus acupuncture group and treated for a period of 6 weeks. Functional mobility, power, and pain were assessed by a blinded assessor using the Constant Shoulder Assessment, at baseline, 6 weeks and 20 weeks. Analysis was based on the intention-to-treat principle. Compared with the exercise group, the exercise plus acupuncture group experienced significantly greater improvement with treatment. Improvements in scores by 39.8% (standard deviation, 27.1) and 76.4% (55.0) were seen for the exercise and the exercise plus acupuncture groups, respectively at 6 weeks (P=0.048), and were sustained at the 20-week re-assessment (40.3% [26.7] and 77.2% [54.0], respectively; P=0.025). We conclude that the combination of acupuncture with shoulder exercise may offer effective treatment for frozen shoulder. PMID- 11773674 TI - Herbal treatment of insomnia. AB - Insomnia is a common problem requiring appropriate recognition and management. Despite recent advances in the development of newer hypnotics in western medicine, a significant proportion of patients with insomnia, both locally and internationally, consume herbal hypnotics regularly. The safety and efficacy of these herbal remedies remains uncertain. In this paper, details of different herbs used in western and traditional Chinese medicine for the treatment of insomnia are reviewed. Although current data suggests the use of some herbal treatments in insomnia may be efficacious, further laboratory and clinical studies are required. PMID- 11773675 TI - Limb salvage in extensive diabetic foot ulceration-a preliminary clinical study using simple debridement and herbal drinks. AB - Diabetic patients frequently suffer from foot ulcer. In spite of the advances in treating many complicated diseases, amputation is usually the 'cure' for diabetic foot ulcer. Diabetic foot ulcer was treated in this study using Chinese herbal medicine and simple debridement as an alternative to amputation. Limb salvage was successful in 35 of 40 legs. These results encourage continuing research into the treatment of diabetic ulcer using Chinese herbal medicine. PMID- 11773676 TI - Effects of a herbal compound containing bupleurum on human lymphocytes. AB - Bupleurum-containing compounds, such as KY88 Liver Livo are thought to have immunomodulatory effects. This study investigated the effects of KY88 Liver Livo on the mitogenic induction of lymphocytes in vitro. Fifteen healthy human adult volunteers, aged between 20 and 50 years, provided peripheral blood samples from which lymphocytes were obtained by Ficoll-Hypaque centrifugation. The separated lymphocytes were stimulated by phytohaemagglutinin and KY88 Liver Livo in varying concentrations for 72 hours, with greater cluster and colony formation evident compared with lymphocytes in a control preparation. KY88 Liver Livo was also found to induce the secretion of granulocyte-macrophage colony-stimulating factor in a dose-dependent fashion. These preliminary in vitro studies suggest that KY88 Liver Livo may have potential clinical value in the treatment of chronic viral infection and in the management of immunocompromised patients. PMID- 11773677 TI - Mild iodine deficiency and thyroid disorders in Hong Kong. AB - OBJECTIVES: To review evidence of iodine deficiency and clinical thyroid disorders in Hong Kong. DATA SOURCES: Publications on local dietary iodine intake, the iodine content of local food items, and clinical thyroid problems in the Hong Kong population. DATA EXTRACTION: Data was extracted and evaluated independently by the authors. DATA SYNTHESIS: Iodine is an essential nutrient. Iodine deficiency can lead to goitre, hypothyroidism, mental deficiency, and impaired growth. It is now appreciated that determination of goitre incidence in children alone may grossly underestimate the problem of iodine deficiency in a population. In total, the evidence indicates that iodine deficiency exists in Hong Kong, leading to clinical problems of transient neonatal hypothyroidism, goitrogenesis, and thyroid disorders in pregnant women and neonates, as well as thyroid dysfunction in the elderly. CONCLUSION: A supplementation programme aimed at a relatively uniform iodine intake is recommended to avoid deficient or excessive iodine intake in subpopulations. PMID- 11773678 TI - Universal antenatal human immunodeficiency virus testing in Hong Kong: consensus statement. AB - Following the recommendations of the Advisory Council on AIDS, Hong Kong, the Hospital Authority announced plans to introduce universal antenatal screening for human immunodeficiency virus infection and hence, a consensus conference was held to discuss strategies for implementing such screening in Hong Kong. This paper reports the discussions of the consensus conference. The consensus meeting group consisted of 15 clinicians and scientists from Hong Kong, Macau, and Thailand. Seven commonly asked questions concerning mother-to-child transmission of human immunodeficiency virus were selected for discussion by the participating panellists. Information on the laboratory diagnosis of human immunodeficiency virus infection and the efficacy of preventive measures in reducing mother-to child transmission of human immunodeficiency virus were reviewed. Data from local studies was also presented and discussed. The timing, potential problems, and cost issues involved in testing all pregnant women in Hong Kong for human immunodeficiency virus were then considered. PMID- 11773679 TI - Selective foeticide in Hong Kong-lawful or not? AB - There is legal uncertainty as to whether selective foeticide is authorised under section 47A of the Offences Against the Person Ordinance (1967). Medical and legal issues surrounding a case of selective foeticide in a triplet pregnancy are reported. PMID- 11773680 TI - Isolated foetal ascites. AB - The prenatal diagnosis and perinatal outcome of two patients with isolated foetal ascites compatible with chyloperitoneum is described. The foetal ascites resolved spontaneously after delivery with good perinatal outcome in both cases. A good prognosis can be anticipated in such cases. Antepartum and intrapartum interventions are seldom necessary. PMID- 11773681 TI - The monoplace hyperbaric chamber and management of decompression illness. AB - Three cases of decompression illness are reported. Two patients presented with joint pain and skin signs, while one patient presented with joint pain and neurological signs and symptoms. The patients received emergency recompression therapy in a Hong Kong clinic, using a monoplace hyperbaric chamber. All three patients were treated successfully and no residual signs or symptoms were evident on review at 90 days' post-treatment. Issues concerning the use of monoplace and multiplace hyperbaric chambers are also discussed, along with additional clinical applications of the monoplace hyperbaric chamber. PMID- 11773682 TI - Diagnosis and current management of gastrojejunocolic fistula. AB - Gastrojejunocolic fistula is a late complication of gastroenterostomy and is associated with inadequate gastric resection and incomplete vagotomy. In the past, attempted primary repair had high mortality and staged operations were normally performed. We present two cases of gastrojejunocolic fistula and discuss the modern management of this condition. In both cases, improved nutritional support allowed successful one-stage surgical repair to be performed. PMID- 11773683 TI - Severe cow's milk protein allergy in a Chinese neonate. AB - Cow's milk protein allergy is a growing problem in developed countries. We report the case of a Chinese infant, born at term, who presented on day 28 with severe growth failure, chronic diarrhoea, and metabolic acidosis. Investigations supported a diagnosis of cow's milk protein allergy. This was confirmed by withdrawing and reintroducing the relevant infant formula under controlled clinical conditions. Both acidosis and diarrhoea were seen to resolve, and 'catch up' growth was evident after introduction of an elemental infant formula. Early recognition of this problem leads to a rapid 'cure', as seen in this case. However, later presentation with other atopic conditions has been reported. PMID- 11773684 TI - Visualisation of the peritoneum during endoscopic retrograde cholangiopancreatography. PMID- 11773686 TI - Triple vessel stenting for triple vessel coronary disease. AB - BACKGROUND: Randomized clinical trials have established the feasibility of implanting multiple coronary stents and, in selected patients, have measured survival after multiple stenting to be comparable to coronary artery bypass graft surgery (CABG). However, the proportion of candidates for this therapy is unclear. this prospective study was performed to measure the percentage of patients eligible for elective multiple stenting of triple vessel coronary artery disease and to examine their short- and intermediate-term outcomes. METHODS: Between January 1996 and January 1999, percutaneous coronary interventions (PCI) were performed in 6,810 consecutive patients, of whom 115 (1.7%) had triple vessel coronary artery disease treated with > or =3 stents. The mean age of these patients was 62.9 years (range, 35-85 years), 83% were men and 13 patients (11%) were diabetic. The treatment was performed in a single procedure in 80% of patients and 362 vessels were dilated, including the left anterior descending artery in 85%, the right coronary artery in 84%, the left circumflex in 49%, the left diagonal artery in 27%, the posterior descending artery in 8% and the posterior lateral artery in 4% of patients. RESULTS: A total of 483 stents were implanted, representing an average of 4.2 +/- 1.4 stents per patients (range, 3 10 stents). The total length of stents averaged 66.9 +/- 4.9 mm. In-hospital adverse events included 2 deaths (1.7%), 2 emergency CABG (1.7%) and 5 myocardial infarctions (4.3%). The mean hospitalization duration was 2.7 +/- 2.2 days. During a follow-up ranging between 1 and 36 months (mean, 16.7 months), 2 patients died (1.7%), 2 patients underwent CABG (1.7%) and 22 patients (19.1%) underwent further coronary artery dilatations. The 3-year event-free survival was 71.3%. In univariate analysis, patients who underwent additional target vessel revascularization were younger and were more likely to have stented segments > 80 mm in the index procedure. No other clinical, angiographic or procedural characteristic was predictive of adverse events. CONCLUSIONS: In this consecutive series of patients undergoing elective PCI, candidates for stenting of > or =3 arteries were few. Most eligible patients underwent uncomplicated and immediately successful procedures. The long-term outcome was comparable to controlled studies of CABG, except for a higher rate of repeat revascularization procedures due to restenosis. PMID- 11773687 TI - Stenting in patients with multivessel disease: the new eon? PMID- 11773688 TI - Novel femoral artery puncture closure device in patients undergoing interventional and diagnostic cardiac procedures. AB - BACKGROUND: The wide range of closure devices for arterial access sites still leaves room for improvement. METHODS AND RESULTS: We report our initial experience with a novel, cost-effective, suture-mediated device (6 French X-PRESS device, X-SITE Medical, Blue Bell, Pennsylvania) for closure of the arterial access site after both diagnostic and therapeutic interventions. A total of 51 consecutive patients are reported. The closure was performed immediately after the procedure. No patient had more than 5,000 U heparin administered during the procedure. The closure device was used in 36 patients (73%) after diagnostic angiography and in 15 patients (27%) after therapeutic intervention. The device could be successfully deployed in 48 patients (94%). In the remaining 3 cases (6%), hemostasis was achieved with standard manual compression without any further event. Immediate total hemostasis was achieved with the device in 44 of 48 patients (92%). Four devices (8%) could not be deployed correctly due to technical problems and the patients needed additional manual compression. The average time to achieve complete hemostasis was 5.5 +/- 3.5 minutes (range, 3-26 minutes). The patients were ambulated after a period of 1.3 +/- 0.4 hours of bedrest (range, 0.8-3.5 hours). Time to possible discharge was 4.2 +/- 3.4 hours (range, 0.9-12.5 hours). One patient experienced a minor complication (hematoma < 6 cm) and was treated with manual compression without clinical sequelae. Telephone follow-up was carried out 2 weeks after deployment and revealed no sequelae. CONCLUSION: The 6 French X-PRESS device is safe and effective in providing rapid hemostasis following interventional or diagnostic catheterization procedures. Use of the device is associated with a low rate of complications and facilitates quick hemostasis, mobilization and discharge. PMID- 11773689 TI - A stitch in time saves nine. PMID- 11773690 TI - Acute angiographic and clinical results of the NIR w/SOX stent. AB - Acute angiographic and clinical results of the NIR w/SOX stent (Boston Scientific/Scimed, Inc., Maple Grove, Minnesota) were evaluated. Between March 2000 and May 2000, a total of 102 lesions in 88 patients underwent stenting with the NIR w/SOX stent. The reference vessel diameter and lesion length were 2.97 +/ 0.50 mm and 16.2 +/- 6.5 mm, respectively. The minimal lumen diameter increased from 0.68 +/- 0.45 to 3.07 +/- 0.50 mm. Stent delivery failure was observed in 4 lesions (3.9%). On the other hand, the NIR w/SOX stent was successfully delivered in 7 of 9 lesions that had unsuccessful delivery of other kinds of stents. Angiographic success was observed in all except 1 lesion where the NIR w/SOX stents could not be delivered. There were no procedural myocardial infarctions or deaths. In one case, procedural coronary bypass surgery was performed. There was no acute closure or subacute stent thrombosis. Despite unfavorable lesion characteristics, the NIR w/SOX stent achieves high procedural success and acceptable stent delivery. Furthermore, it may have a high probability to be delivered in lesions where other kinds of stent result in unsuccessful delivery. PMID- 11773691 TI - Noninvasive assessment of coronary artery bypass graft patency and flow characteristics by electron-beam tomography. AB - OBJECTIVE: To evaluate the flow characteristics and accuracy for the detection of patent or occluded coronary artery bypass grafts (CABG) with multi-slice flow study of electron-beam tomography (EBT). METHODS: One hundred and twenty-three patients who had undergone CABG surgery were enrolled in this study. Flow datasets were assessed with time-density curves by EBT. The EBT results were blindly compared with post-operative cardiac catheterizations in 26 patients. RESULTS: Image quality was adequate to evaluate in 111 patients (90.2%). Flow curves of bypass grafts were technically adequate in 265 of 309 (85.8%) saphenous vein grafts (SVG) and 35 of 56 (62.5%) internal mammary artery (IMA) grafts (p < 0.05). In comparison to conventional angiographic results, EBT correctly identified 14 of 16 occluded grafts (sensitivity, 87.5%) and 68 of 75 patent grafts (specificity, 90.7%), yielding an accuracy of 90.1%. The intra-graft flows of the IMA and SVG were 4.9 +/- 2.2 ml/min/g and 6.9 +/- 2.8 ml/min/g, respectively (p < 0.001), which was 31.6 +/- 20.4% and 39.4 +/- 21.9% of the ascending aorta's flow (16.7 +/- 5.0 ml/min/g) (p < 0.001). CONCLUSION: EBT flow study can be used in the assessment of CABG patency and quantification of intra graft flow of patent CABG vessels. PMID- 11773692 TI - Percutaneous catheter closure of secundum atrial septal defects: a review. AB - Attempts at catheter closure of atrial septal defects began over 3 decades ago. Several devices have been designed attempting to achieve this objective safely and effectively. These devices have been (or are being) subjected to extensive clinical trials. This review outlines the background and current status of these devices. It addresses the design, delivery method, results and complications. In addition to historical background, the devices discussed here include (in alphabetical order) the Amplatzer Septal Occluder, the Atrial Septal Defect Occlusion System, the Buttoned Device, the Guardian Angel (Angel Wings), the Helex Septal Occluder, the StarFlex (Cardioseal, Clamshell), and transcatheter patch closure of atrial septal defects. These devices have come a long way to avoid potential complications and a number of them show very promising results. Issues to consider when choosing the device/atrial septal defect compatibility are also discussed. It is hoped that a number of these devices will be available in the near future to allow the physician and patient to choose the most appropriate method or device. PMID- 11773693 TI - Endovascular stent placement for management of total renal artery occlusion in a child. AB - Total renal artery occlusion is a rare complication of percutaneous transluminal angioplasty. An 8-year-old boy was referred due to left renal artery stenosis after unsuccessful balloon angioplasty. Total left renal artery occlusion was diagnosed by angiography. The combination of balloon angioplasty and stent placement allowed reestablishment of perfusion and salvage of a severely threatened kidney. His blood pressure improved after the procedure and returned to normal 3 months later. The patient has remained free of symptoms for 12 months without medication. PMID- 11773694 TI - Transrenal bare stents in endovascular treatment of abdominal aortic aneurysms. AB - Endovascular stent-graft (EVSG) repair of abdominal aortic aneurysms (AAA) has continued to evolve since its introduction in 1991. The ability to secure a stent graft in the suprarenal aorta with an uncovered proximal stent is felt by many to improve the overall fixation of the device and decrease the risk of migration and endoleak. While preliminary evidence suggests that type I endoleaks may be less frequent when transrenal bare stents are used, this has yet to be conclusively shown. Of obvious concern is the risk of renal parenchymal damage or diminished blood flow following placement of a bare stent across the renal artery ostia. Numerous small series have shown little or no risk of significant renal impairment at intermediate length of follow-up after transrenal stent placement. The presence of a stent across the renal artery orifice does not appear to interfere with later interventions on that artery, such as angioplasty and stenting. PMID- 11773695 TI - Left anterior descending coronary artery to right ventricular fistula complicating coronary stenting. AB - Coronary artery perforation is a rare complication of percutaneous transluminal coronary angioplasty (PTCA) and coronary stenting, most commonly creating a communication between the coronary artery lumen and the pericardial space. We report a case where vessel rupture following stent deployment led to the development of a fistula between the left anterior descending coronary artery and the right ventricle. PMID- 11773696 TI - Successful interventional treatment of an octogenarian presenting with syncope and Ebstein's anomaly of the tricuspid valve. AB - Syncope is a frequent occurrence in the elderly and cardiac causes are common. Therefore, accurate diagnosis is essential since specific treatments are often required. We present an 85-year-old woman with recurrent syncope secondary to sinus node reentrant tachycardia (SNRT), which was successfully treated by radiofrequency ablation. This is the first reported description of SNRT and its successful treatment in Ebstein's anomaly. Atrial arrhythmias and accessory atrioventricular bypass pathways are common in Ebstein's anomaly and are briefly discussed. Our patient is alive at age 87, which is exceptional for Ebstein's anomaly. PMID- 11773697 TI - Cardiac resynchronization therapy for treatment of chronic heart failure. AB - Cardiac resynchronization therapy (CRT) by means of biventricular pacing is a fairly new procedure that has recently been approved by the United States Food and Drug Administration. Many promising studies have been published that suggest CRT improves patient quality of life (based on the Minnesota Living with Heart Failure Quality of Life Questionnaire), increases distance walked in 6 minutes, improves oxygen uptake, lowers New York Heart Association classification, decreases QRS duration, increases left ventricular ejection fraction, and increases peak oxygen consumption. These studies include the Multisite Stimulation in Cardiomyopathies (MUSTIC), the Multicenter InSync Randomized Clinical Evaluation (MIRACLE), the Pacing Therapy for Congestive Heart Failure (PATH-CHF) multicenter trial, the Medtronic Inc. InSync study, the Ventak CHF/Contak CD study, Vigor CHF and a small study conducted by Alonso and colleagues. There are also a number of studies that are still being conducted, such as the COMPANION trial, which will provide further insight into the effectiveness of cardiac resynchronization therapy. PMID- 11773698 TI - The bent stent. PMID- 11773699 TI - The "Panic Stent": a stent that goes everywhere, all the time, with any guidewire, any guiding catheter and with any operator. PMID- 11773700 TI - Mechanism of basic fibroblast growth factor-induced cell death. AB - Basic fibroblast growth factor (bFGF) is a potent mitogen for a number of different cell types. Its over-expression has been implicated in transformation and malignant progression. The use of bFGF to treat malignancy is therefore counterintuitive. However, recent studies have shown bFGF-induces cell death in some tumour types. This mini review will summarise the most recent findings on bFGF-induced cell death and discuss its potential mechanism of action. PMID- 11773701 TI - Structure and function of GC79/TRPS1, a novel androgen-repressible apoptosis gene. AB - Expression of death-signaling genes induces many biochemical cascades resulting in elimination of cells via apoptosis or programmed cell death. GC79/TRPS1 is a novel apoptosis associated gene that encodes a multitype zinc finger GATA-type transcription factor. Expression of GC79/TRPS1 is repressed in the rat ventral prostate and significantly elevated after androgen withdrawal by castration. Castration leads to regression of the prostate caused by apoptosis of androgen dependent prostate cells. Prostate cancer consists of androgen-dependent and androgen-independent cells. The androgen-independent cells, usually present in the prostate of advanced prostate cancer patients do not have the ability to undergo apoptosis after androgen withdrawal. GC79/TRPS1 expression in androgen dependent prostate cancer cells is repressed by androgens, while GC79/TRPS1 expression is hardly detectable in androgen-independent prostate cancer cells under cell culture conditions. This suggests that lack of GC79/TRPS1 expression could be a mechanism for the inability to induce the apoptotic pathway in androgen-independent prostate cancer cells after androgen withdrawal. This review will focus on the current knowlegde of the structure and function of GC79/TRPS1, a novel androgen-repressible apoptosis gene. PMID- 11773702 TI - Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment. AB - Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Survivin has been reported to be expressed in many cancers, but not in differentiated normal tissue. Recent studies revealed that survivin correlated with the chemo resitance of cancer cells. In the present study, the changes in expression levels of survivin messenger RNA (mRNA) and survivin protein in a gastric cancer cell line (MKN-45) during cisplatin (CDDP) treatment were analyzed and compared with the occurrence of apoptotic cell death. Cell growth was inhibited even with a low dose CDDP (0.1 or 1 microg/ml) 1 hr treatment. However, the percentage of apoptotic cells did not change after 48 hr incubation with low dose CDDP. Only with high dose CDDP (10 microg/ml), did the percentage of apoptotic cells explosively increase between 12 and 24 hr treatment. Relative expression levels of survivin mRNA and survivin protein increased after CDDP treatment. The cell expression rates of survivin mRNA after 48 hr treatment with 0.1 and 1 microg/ml of CDDP were 2 to 6 fold higher than that of the survivin mRNA of untreated cells. Also, the relative cell expression level of survivin protein after 24 hr treatment with 0.1 or 1 microg/ml of CDDP was 3 to 6.5 fold higher than that of the survivin protein of untreated cells. These results indicate that survivin expression may correlate with the chemo-resistance of malignant cells. PMID- 11773703 TI - Inhibition of protein phosphatase-1 is linked to phosphorylation of p53 and apoptosis. AB - p53 is a multifunctional protein and its activity can be modulated by phosphorylation and dephosphorylation. In this study, we sought to examine the notion that serine/threonine phosphatases (PP-1 and PP-2A) are active modulators of the p53-dependent apoptotic pathway. Exposure of neonatal rat cardiomyocytes to the established apoptotic agents, bafilomycin A1 (BAF) or staurosporine (STAU) induced apoptosis and caused a decrease in PP-1 activity of 35%. This response was restricted to apoptotic stimuli as treatment with phenylephrine neither decreased PP-1 and PP-2A activity nor induced DNA fragmentation in cardiomyocytes. The level of phosphorylated p53 was increased as a result of BAF or STAU-treatment. We further examined the effect of PP-1 inhibition on cardiomyocytes by the use of the phosphatase inhibitor, okadaic acid, and an antisense strategy. Okadaic acid (100 nM) resulted in a decrease in PP-1 activity of 45%, enhanced phosphorylation of p53, and stimulated apoptosis. Furthermore, overexpression of the antisense PP-1 catalytic subunit transcript caused a 44% decrease in expression of PP-1, with no change in the levels of the PP-2A catalytic subunit, and also evoked DNA fragmentation. Our data support the view that decreased activity of PP-1 is an important signaling event in the apoptotic process. PMID- 11773704 TI - Annexin V expression in apoptotic peripheral blood lymphocytes: an electron microscopic evaluation. AB - Loss of plasma membrane asymmetry, resulting in the exposure of phosphatidylserine (PS), is considered to be an 'early' event in apoptosis. It is generally accepted to precede nuclear condensation, independent of the apoptosis inductive agent. In the present study we focus on 2 apoptotic parameters: PS exposure in comparison with morphological alterations. Peripheral blood lymphocytes were irradiated in vitro (5 Gy Co-gamma-rays) or incubated with staurosporine (1 microM, 6 hours). PS exposure was measured flow cytometrically using FITC-labelled annexin V, combined with PI. Morphological alterations were evaluated by electron microscopy (EM). Results are based on 3 independent experiments. For the irradiated lymphocytes the amount of viable cells (annexin V /PI-) as scored by flow cytometry was comparable or slightly lower than the number of viable cells as scored by EM (75% compared to 79%). However, for the staurosporine treated lymphocytes only about 24% of the cells were designated as viable by EM, whereas by flow cytometry about 65% of the cells were annexin V-/PI . Examination by EM showed about 40% cells with a morphology distinct from that of a normal viable cell, but without the clear-cut characteristics of apoptotic cells. Time studies revealed that these cells went into apoptosis after prolonged incubation times up to 18 hours. Application of biotinilated annexin V for EM detection with gold-conjugated anti-biotin, showed that only clear-cut apoptotic, apoptotic necrotic and oncotic cells showed the gold-label at their membranes. Cells that could be detected under the EM as 'non-viable' but without the clear cut characteristics of apoptotic cells, were not labelled. Data indicate that, dependent on the apoptosis inductive mechanism, morphological alterations can occur before PS exposure. PMID- 11773705 TI - Protein A-activated macrophages induce apoptosis in Ehrlich's ascites carcinoma through a nitric oxide-dependent pathway. AB - Protein A (PA) of Staphylococcus aureus has been demonstrated to possess anti tumor activity against a wide variety of tumors. In the current study we endeavored to obtain a mechanistic insight into PA-mediated Ehrlich's ascites carcinoma (EAC) killing. Our results indicate that PA stimulates generation of nitric oxide (NO) from murine peritoneal macrophages. Nitric oxide in turn induces cytotoxic damage to the tumor cells. Analysis of the morphological features and cell cycle phase distribution pattern of nuclear DNA revealed an induction of apoptosis (appearance of sub-G0/G1 population) in EAC after PA treatment. We have further elaborated the alterations in the expressions of the proto-oncoproteins p53 and Bax, together with a change in the ratio of Bcl-2/Bax in the treated tumor cells, which favor apoptosis. PA-induced apoptosis and changes in the expression of oncoproteins in the tumor cells was prevented by the suppression of NO release by the addition of L-NAME, the competitive NOS inhibitor, suggesting a possible mechanism by which PA exerts its anti-tumor activities involving nitric oxide through the alteration in the expressions of pro-apoptotic proteins. PMID- 11773706 TI - Etoposide-induced apoptosis in lymphoblastoid leukaemic MOLT-4 cells: evidence that chromatin condensation, loss of phosphatidylserine asymmetry and apoptotic body formation can occur independently. AB - Apoptosis is characterised by a series of typical morphological features, such as nuclear and cellular convolution, chromatin condensation and the final disintegration of the cell into membrane-bound apoptotic bodies, which are phagocytosed, by neighbouring cells. Relocation of phosphatidylserine residues from the inner leaflet of the cellular membrane to being exposed on the cell surface is a necessary event for the phagocytic elimination of apoptotic cell debris. Using the MOLT-4 lymphoblastoid leukaemic cell line we investigated whether the formation of apoptotic bodies and loss of phosphatidylserine asymmetry were causally related. We have previously demonstrated that classical apoptotic morphology, including production of apoptotic bodies, was only possible in etoposide-treated MOLT-4 cells when administered in the presence of non cytotoxic doses (200 microM) of aurin tricarboxylic acid (ATA). Electron microscopic analysis, followed by the quantitation of the ultrastructural morphological features of apoptotic MOLT-4 cells, demonstrated that the etoposide and ATA co-treatment, which caused the cellular fragmentation into apoptotic bodies, was closely associated with extensive chromatin condensation in individual cells. In this model however, the addition of ATA to frank cytotoxic doses of etoposide (50 microM), which we confirmed lead to formation of apoptotic bodies, caused no further increase in externalisation of phosphatidylserine moieties as determined by staining with fluorescence labelled annexin V. Consequently, in MOLT-4 cells undergoing etoposide-induced apoptosis, the mole cular mechanisms leading to loss of phosphatidylserine asymmetry and the formation of apoptotic bodies are not causally related. PMID- 11773707 TI - Phosphoinositol 3 kinase inhibitor, LY294002 increases bcl-2 protein and inhibits okadaic acid-induced apoptosis in Bcl-2 expressing renal epithelial cells. AB - Protein phosphorylation plays an indispensable role in cellular regulation of mitosis, metabolism, differentiation, and death. We previously reported that the protein phosphatase inhibitor okadaic acid (OKA) induces apoptosis in renal epithelial cells in culture. In the present study, we examined the role of phosphotidylinositol 3 (PI3) kinase signaling in okadaic acid-induced apoptosis by pre-treating normal rat kidney renal epithelial cells expressing human bcl-2 with the PI3 kinase inhibitors, LY294002 and wortmannin, followed by apoptosis inducing concentrations of okadaic acid. Given the reported cell survival activity of PI3 kinase signaling mostly attributed to Akt kinase activation, we hypothesized that inhibition of PI3 kinase would enhance okadaic-induced apoptosis. Surprisingly, our data show that pretreatment with LY294002, but not wortmannin, attenuated okadaic acid-induced apoptosis. In contrast, to LY294002, wortmannin enhanced apoptosis. Interestingly, we also found that LY294002 treatment increased bcl-2 protein levels in normal rat kidney epithelial cells expressing bcl-2 (NRK-bcl-2). In untreated cells, bcl-2 appeared to be mainly perinuclear, coincident with the nuclear membrane, or in the cytosol. In OKA treated cells that were pre-treated with Ly294002, bcl-2 was highly co-localized with mitochondria, but in cells treated with okadaic acid alone, bcl-2 was associated with fragmented chromatin. In this model, it appears that LY294002 may exert anti-apoptotic effects by a previously unreported treatment related increase in bcl-2. Although it is widely accepted that bcl-2 protein can inhibit apoptosis, we propose that the subcellular location of bcl-2 is an important determinant in whether bcl-2 effectively inhibits apoptosis. PMID- 11773708 TI - Process of apoptosis induced by TNF-alpha in murine fibroblast Ltk-cells: continuous observation with video enhanced contrast microscopy. AB - Apoptosis is originally defined by unique morphological changes of dying cells, and the biochemical hallmark associated with apoptosis is internucleosomal DNA fragmentation. However, few report has shown the precise time course of the apoptotic events. The present study was designed to try to clarify apoptotic processes using a video-enhanced contrast-differential interference contrast (VEC DIC) microscopy. The morphological changes of murine fibroblast Ltk-cells treated with TNF-alpha were divided into four stages: (i) pre-apoptotic, (ii) cytoplasmic shrinkage, (iii) membrane blebbing, and (iv) ballooning. Almost of the cells underwent cytoplasmic shrinkage and membrane blebbing within 6 hours after TNF alpha exposure, and at about 9 hours, they were in the ballooning stage. Based on these data, we investigated the relationship between morphological changes and other biochemical features. The earliest event was exposure of phosphatidyl serine at the cytoplasmic membrane, which was already observed in the pre apoptotic stage. Loss of mitochondrial membrane potential was observed in the cytoplasmic shrinkage stage. Caspase-8/-3 activities already started increasing in the pre-apoptotic stage, and reached their peak at 6 hours after TNF-alpha exposure. DNA fragmentation occurred in the late phase of the membrane blebbing. PMID- 11773709 TI - Hypertension at elderly age: what we know and what we must learn. PMID- 11773711 TI - Treatment of hypertension in the elderly. AB - Hypertension is a common condition among older people in most developed countries, and is a very important, if not the most important, risk factor for all subtypes of vascular disease and death. Many clinical trials in older people have demonstrated significant reductions in myocardial infarctions and strokes when antihypertensive drugs are provided. Lifestyle modifications are still recommended because they can lower a surrogate end point--blood pressure--but there are no data showing they reduce event rates. It is not appropriate to limit the choice of initial drug for hypertensive older individuals to a single class of agents, since so many older people have other medical problems that affect this decision. Monotherapy with an alpha blocker, however, is no longer recommended, even for men with hypertension and benign prostatic hypertrophy, as doxazosin was associated with a higher rate of cardiovascular events in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The classic strategy of an initial diuretic (for at least 1 month) will likely be verified by the final results of ongoing randomized trials, expected in 2003. Until then, this strategy is effective, inexpensive, and unlikely to cause many adverse effects. Probably the most important exhortation, however, should be to achieve the blood pressure goal appropriate for the patient's risk status. Numerous clinical trials in older hypertensive patients have shown that more benefits accrue when the goal blood pressure is achieved than if a specific antihypertensive agent is chosen as initial therapy. Future cardiovascular risk may be related directly to the blood pressure attained, rather than to how it was attained. PMID- 11773712 TI - Epidemiology of hypertension in the elderly. AB - In Western populations, mean systolic and diastolic blood pressures rise with advancing age up to the sixth decade of life, whereupon systolic blood pressure continues to increase and diastolic pressure starts to decline. The ensuing widening of pulse pressure is mainly ascribed to stiffening of the arterial vasculature. When hypertension is defined as systolic blood pressure of at least 140 mm Hg and/or diastolic pressure of at least 90 mm Hg, its prevalence amounts to 60%-70% of the population above 60 years of age. About 60% of these hypertensives have isolated systolic hypertension--that is, elevated systolic pressure and normal diastolic pressure. It should be realized, however, that approximately 25% of those labeled hypertensive on the basis of conventional blood pressure measurements have normal blood pressure on ambulatory blood pressure monitoring, or so-called white-coat, isolated clinic, or nonsustained hypertension. There is little doubt that elevated blood pressure leads to a number of cardiovascular complications. Whereas diastolic blood pressure has been emphasized for many years, the paradigm has shifted toward systolic blood pressure. In addition, pulse pressure has been shown to be an important predictor of cardiovascular events and death, above and beyond the predictive power of mean blood pressure. PMID- 11773713 TI - Modifications of the cardiovascular system with aging. AB - Aging is accompanied by significant cardiovascular modifications, both structural and functional. A slight degree of left ventricular hypertrophy develops, while the resting heart rate and early filling rate are somewhat decreased. In contrast, end-diastolic and end-systolic dimensions, stroke volume, and ejection fraction are largely unchanged. The effort tachycardic and inotropic responses are clearly attenuated, whereas the concomitant increase in end-diastolic diameter is enhanced. Large arterial conduits become less distensible and somewhat hypertrophic. Total blood volume is reduced, whereas total peripheral resistance is moderately increased. Neurohumoral systems relevant to cardiovascular regulation are nonuniformly affected by aging: the sympathetic nervous system is overactive and the circulating levels of vasopressin and atrial natriuretic factor are enhanced, while the activity of the renin-angiotensin system is blunted. Elderly individuals have altered cardiovascular homeostasis, with a typical propensity to postural and postprandial hypotension. "Spontaneous" blood pressure variability is increased, whereas heart rate variability is diminished. Vagally mediated chronotropic responses, including those dependent on baroreflex modulation, are attenuated, although end-organ (cardiac) parasympathetic responsiveness is exaggerated. Arterial baroreceptor control of blood pressure is largely preserved in advanced age, whereas cardiopulmonary mediated reflex responses are definitely impaired. PMID- 11773714 TI - Pathophysiology of hypertension in the elderly. AB - Systolic hypertension is the most common type of hypertension in the elderly and a major modifiable cardiovascular risk factor. Systolic hypertension is associated with a wide pulse pressure resulting largely from excessive large artery stiffness. Arterial stiffness increases with age independently of mean blood pressure or the presence of other risk factors. In this review, the authors discuss the effects of age and blood pressure on arterial stiffness, the physiology of arterial compliance, and the anatomic changes of large arteries with aging. In most studies reported in the literature, elderly populations are relatively small. The role of both age and gender on arterial stiffness and wave reflection has been poorly investigated, particularly in subjects over 70 years. In this elderly population, further research is needed concerning the pathophysiology, epidemiology, and pharmacology of hypertension. PMID- 11773715 TI - Results of antihypertensive treatment trials in the elderly. AB - The prevalence of arterial hypertension is age-dependent, and with the prolongation of life expectancy the number of elderly subjects with arterial hypertension is very relevant. Epidemiologic studies have shown that arterial hypertension is a risk factor in elderly patients and therefore the physician must know if the pharmacologic and nonpharmacologic reduction of blood pressure values is associated with a corresponding decrease in systolic-diastolic or isolated systolic hypertension. Clinical trials have shown that the lowering of blood pressure values is commonly associated with a decrease in cardiovascular events. So far, the reduction of blood pressure per se appears more relevant to the cardiovascular benefit than does a particular class of antihypertensive agents. The benefit of antihypertensive treatment has been shown up to the age of 80 years, while there are no clear indications of a benefit in persons older than 80 years. While sufficient data suggest that a diastolic blood pressure between 80 and 90 mm Hg is associated with a clear benefit in elderly patients, the data in support of a systolic reduction below 140 mm Hg require further direct confirmation. PMID- 11773716 TI - Rhabdomyolysis and statin therapy: relevance to the elderly. AB - A recent debate has emerged as to the risk-benefit ratio of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). This debate has centered on the withdrawal of the HMG-CoA reductase inhibitor cerivastatin (Baycol). Its withdrawal was prompted by an unacceptably high rate of rhabdomyolysis associated with its use. The development of rhabdomyolysis in cerivastatin-treated patients surprised few, since myotoxicity is a class effect with HMG-CoA reductase inhibitors. What has sprung from the cerivastatin experience, though, is the concept of "guilt by association"; thus, other members of this class are now viewed in a similarly negative light. Such misgivings are understandable, but to a degree may be ill-advised, since differences exist in the risk and therefore the rate of rhabdomyolysis occurrence among the various HMG-CoA reductase inhibitors. In this regard, pravastatin and fluvastatin are least likely to provoke muscle cell damage, which, at least in part, relates to their not being metabolized by the cytochrome P-450 (CYP) 3A4 pathway. When muscle damage does occur with HMG-CoA reductase inhibitors, it is commonly the result of drug-drug interactions rather than a specific adverse response to HMG CoA reductase inhibitor monotherapy. Such drug-drug interactions inevitably result in higher plasma concentrations of an HMG-CoA reductase inhibitor and thereby an increased risk of myotoxicity. A growing consensus supports an expanded use of HMG-CoA reductase inhibitors in elderly patients. Polypharmacy and altered drug metabolism both put the elderly patient at increased risk of myotoxicity when drugs in the HMG-CoA reductase inhibitor class are administered. Physicians must take many factors into account when selecting a member of the HMG CoA reductase inhibitor class, particularly as relates to their use in the multiply medicated elderly patient. PMID- 11773717 TI - Ethical issues in the management of geriatric cardiac patients. AB - A neurosurgeon takes extraordinary measures to convince family members to act against a hospice patient's express wishes. PMID- 11773718 TI - Ten-beat (atypical) Wenckebach period. PMID- 11773719 TI - Hyperlipidemia in the elderly: two new observations. PMID- 11773720 TI - Left atrial appendage thrombus in transit with peripheral embolization. PMID- 11773721 TI - Angiotensin II (AT(1)) receptor antagonists, diabetes, and nephropathy: do differences between the renal and systemic circulations explain the outcomes observed with ARBs and ACE inhibitors? PMID- 11773722 TI - In Memoriam: John Eugene Smialek, M.D., 1943-2001. PMID- 11773723 TI - Safety of titanium mesh for orbital reconstruction. AB - During the past several decades, the standard of care for orbital reconstruction after trauma has been autogenous bone grafts. Complications of bone grafts, including donor site morbidities such as scar alopecia and graft resorption with delayed enophthalmos, have inspired an interest in the use of alloplastic substitutes such as titanium. Titanium's role in orbital reconstruction was limited originally to small orbital defects, and as an adjunct to bone grafts. More recently, clinical studies have documented the sole use of titanium mesh to reconstruct large orbital defects. This study sought to document further the safety and efficacy of titanium mesh in reconstructing large orbital defects after facial trauma, with more extensive follow-up compared with previous studies. In the current study, 55 patients with 67 orbital fractures underwent orbital reconstruction with titanium mesh over a 5-year period. Associated fractures were reduced anatomically and fixed rigidly. For the analysis, 44 patients with 56 orbital fractures had adequate follow-up (mean, 44 months). An abscess developed in one patient who received high-dose steroids for 72 hours before reconstruction. She was treated with broad-spectrum intravenous antibiotics and bedside incision and drainage, and did not require removal of the titanium mesh. No patient in the current series required removal of the titanium mesh. A single case of uncorrected enophthalmos was treated with bone grafting rather than mesh revision. Large orbital defects can be reconstructed using titanium mesh with good functional results and minimal risk for infection. This study covered the authors' first 5 years using titanium. They have now used titanium mesh in orbital reconstructions for more than 10 years, without any additional cases of infection. PMID- 11773725 TI - Endoscope-assisted management of varicose veins in the posterior thigh, popliteal fossa, and calf area. AB - Varicose veins of the posterior thigh, popliteal fossa, and calf area were managed with the assistance of endoscopic surgery in 136 patients. Patients were divided into four types according to the normal veins involved in varicosities. With good illumination and magnified monitor viewing by means of a surgical endoscope, the main channel, tributaries of varicosities, incompetent perforating veins, and healthy veins could be clearly visualized and identified. Even though these varicosities had aberrant and tortuous courses, they could be completely dissected, divided, and then removed through one or more access incisions (2.5 3.0 cm in length). The incompetent perforating veins were also dissected and divided. The mean number of access incisions for each lower extremity was 2.2, 1.9, 1.3, and 1.0 for types I, II, III, and IV respectively. In all cases, the mean number of incisions was 1.6 in each lower limb. The most frequent morbidity was maceration of the access incision. Three wounds in 3 patients required debridement and resuturing, but the other wounds healed satisfactorily. Transient discoloration caused by bruising and numbness may present at the dissected area. There was no hematoma formation. Ischemic change with bleb formation of the dissected skin occurred in 1 patient. Subsequent secondary healing resulted in slight scarring in this area. With the assistance of endoscopic surgery, all the varicosities and the incompetent perforating veins could be completely dissected and removed. Accomplishment of removal of varicosities was double-checked between the preoperative skin marks of varicosities and the endoscopic findings. There is very little possibility for recurrence, because there were no residual varicosities or incompetent perforating veins after this operation. There was no recurrence in follow-up at least 2 months postoperatively. Patients were satisfied with the minimal surgical scarring and the complete absence of disfiguring varicosities. PMID- 11773726 TI - Reliability of primary vein grafts in lower extremity free tissue transfers. AB - Free flaps transferred to the lower extremity have a higher risk of failure, which may be expected to increase further with the use of vein grafts. The results of 103 consecutive free flaps to the lower extremities of 98 patients who were operated from March 1994 to December 1999 were evaluated to assess the reliability of vein grafts in lower extremity reconstruction. Five flaps were lost and the overall success rate was 95.1%. Eighty-four free tissue transfers in 79 patients were performed for the reconstruction of traumatic cases, and 81 of these flaps were performed in a delayed manner, between 1 week and 4 months after the injury. Interpositional vein grafts were used primarily in 22 flaps--all in traumatic cases--and 21 of them survived completely (95.4%). Primary vein grafts were used both for arteries and veins in 15 flaps and for arteries only in 7 flaps. The most common cause of tissue loss in these patients was a crush injury in earthquake survivors, followed by electrical injuries, gunshot injuries, motor vehicle accidents, and chronic infections. Free muscle flaps in 13 patients, skin flaps in 4 patients, osseous flaps in 2 patients, and temporal fascial flaps in 2 patients were the flaps of choice in vein graft reconstructions. Although a higher incidence of flap loss has been reported with the use of interpositional vein grafts than with regular transfers, and the technical and pathophysiological problems in flap transfers are also high in the lower extremity, the success rate in vein-grafted free flaps did not differ from that of the simple free flap transfers in the current series. This appears to be the result of meticulous preoperative planning and proper selection of recipient vessels during optimal operative conditions. PMID- 11773727 TI - Anatomic variations related to decompression of the common peroneal nerve at the fibular head. AB - Peroneal nerve decompression at the fibular head may be anticipated to be performed more often because lower extremity peripheral nerve surgery is used to restore sensation to the feet of diabetic patients. Although the basic concept of releasing the fascia of the peroneus longus is well-known, anatomic variants related to the peroneus muscle have been identified that must be included in the technique for decompression of this nerve. A comparison of these anatomic variants was done between a random selection of 29 cadavers (bilateral) and 65 patients who underwent unilateral peroneal decompression to treat symptoms of that compression. A fibrous band on the undersurface of the superficial head of the peroneus longus was found in 30% of the cadavers and it was found in 78.5% of the patients. The mean width of the band in cadavers was 9.1 mm and in patients it was 10.1 mm. A fibrous band on the superficial surface of the deep head of the peroneus longus was found in 43% of cadavers, and it was found in 20% of the patients. The soleus muscle origin was joined to the peroneus muscle origin in 9% of cadavers and it was noted in 6% of the patients. It is suggested that during surgical decompression of the common peroneal nerve at the fibular head, the surgeon be aware of these anatomic variants so that they may be released appropriately. PMID- 11773728 TI - Management of neuromas in continuity of the median nerve with the pronator quadratus muscle flap. AB - Treatment of painful neuromas in continuity of the median nerve at the wrist level is a challenging problem. Nine median nerve neuromas were covered with the pronator quadratus muscle preelevated as an island flap. Patients were followed for 10 to 60 months after surgery. Results showed a marked improvement in terms of symptoms in all patients. In particular, 6 patients had complete pain relief and 3 patients complained of mild intermittent pain. PMID- 11773729 TI - Microsurgical medialis pedis flaps for reconstruction of soft-tissue defects in the hand. AB - The medialis pedis flap (MPF) has been used for the reconstruction of soft-tissue defects in the hand since 1990. From January 1997 through January 2000, 19 patients (15 male, 4 female) with hand injuries underwent microsurgical MDF reconstruction at Chang Gung Memorial Hospital. There were finger injuries in 16 patients and palm defects in 3 patients. The mean patient age was 32.6 years (age range, 16-58 years). Flap size ranged from 4.5 x 2 cm to 7 x 6 cm (mean, 6 x 2.8 cm). Only one flap had partial loss. The donor site was closed primarily in 9 patients, and was closed using a split-thickness skin graft in 9 patients and a full-thickness skin graft in 1 patient. At a mean follow-up of 13 months, the protective sensation was 16 mm using the static two-point discrimination test and was 10 mm using the moving two-point discrimination test. Based on this retrospective study the authors conclude that (1) the MPF has the advantages of thin and glabrous skin, (2) the size of pedicle is compatible with the recipient vessel in the hand, (3) there is low donor site morbidity, and (4) achieving protective sensation is possible. PMID- 11773730 TI - Stepladder dorsal metacarpal flaps for dorsal finger and hand reconstruction. AB - The authors demonstrate successful cases of stepladder dorsal metacarpal V-Y advancement and rotation-advancement flaps for reconstructing defects on the dorsum of the finger and hand. One side of the flap is designed in a multilobed shape, and each lobed flap is designed on the dorsum of adjacent fingers. These flaps are supplied by dorsal metacarpal vessels. Consequently, this method has the elements of the stepped incision technique, in combination with the V-Y and rotation-advancement principle. All flaps survived completely. This technique may be a useful option for reconstruction of defects of the dorsum of the finger and hand. PMID- 11773731 TI - Revascularization of transplanted adipose tissue: a study in the dorsal skinfold chamber of hamsters. AB - Adipose tissue seems to be an ideal material for use as a permanent soft-tissue substitute in reconstructive surgery. However, knowledge of the behavior of the graft--in particular, its revascularization--is scarce. Therefore, the aim of the current study was to establish a novel model that allows for long-term in vivo quantitative analysis of revascularization of adipose tissue after transplantation. Hamsters (n = 8) were fitted with transparent titanium dorsal skinfold chambers. Immediately after en bloc harvest of adipose tissue from the left inguinal area, the graft was placed gently into the chamber. At days 1, 3, 12, and 21, red blood cell-perfused vessels were assessed in surrounding host tissue, in the border of the graft, and in its center (n = 6 areas each) using intravital fluorescent microscopy. The model allowed for permanent observations of adipose tissue and quantitative analysis of functional vessel density (FVD). At the border zone of the graft, an FVD of 2 +/- 1 cm per cm(2) was measured at day 1. In this region FVD increased constantly and finally reached values (184 +/ 10 cm per cm(2); day 21) that were comparable with those of the surrounding host tissue. Revascularization in the center of the graft started at day 3 after transplantation (14 +/- 3 cm per cm(2)). Here, FVD increased constantly, but lower values compared with the grafts' border zone were measured (139 +/- 10 cm per cm(2); day 21). FVD data obtained from transplanted adipose tissue may contribute to understanding fundamental mechanisms of graft failure. PMID- 11773732 TI - Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model. AB - The heat shock response is known to have a protective effect against flap ischemia. It has been shown that heat shock protein (hsp) expression can be augmented in vivo with the administration of high-dose aspirin before heat treatment. The authors hypothesized that administration of aspirin before hsp induction through heat stress would enhance further the protective effects of the heat shock response against skin flap ischemia. They used a random dorsal skin flap model in 32 rats divided into four groups (N = 8 each): control, heat shock, aspirin plus heat shock, and aspirin. Before surgery, rats in the two heat shock groups were placed in a 45 degrees C water bath until core body temperature measured 42 degrees C, and they were maintained at 42 degrees C for 15 minutes. Rats in the two aspirin groups received a single oral dose of aspirin (100 mg per kilogram) 1 hour before heat bath or surgery. Immunohistochemistry confirmed hsp expression in the two heat groups. Skin flap survival was improved significantly (p < 0.05) in the heat shock (55%), aspirin plus heat shock (58%), and aspirin (60%) groups when compared with controls (45%). Contrary to their hypothesis, aspirin combined with hsp induction did not offer greater protection from ischemia than hsp induction alone (p > 0.05). However, high-dose aspirin administration alone did improve skin flap survival when compared with controls. Future studies are needed to investigate further the role of pharmacological therapy combined with hsp induction in improving skin flap survival and to delineate the dose-response relationship between aspirin and hsp. PMID- 11773733 TI - Difference of molecular response to ischemia-reperfusion of rat skeletal muscle as a function of ischemic time: study of the expression of p53, p21(WAF-1), Bax protein, and apoptosis. AB - The authors investigated the expression of p53, p21(WAF-1), Bax protein, and apoptosis to elucidate the cellular response to ischemia-reperfusion of skeletal muscle using the rat lower limb model. The rat left lower limb was dissected in the inguinal region, isolating the bony femoral muscles, and the femoral vessels were clamped to produce an ischemic condition. After 3 or 6 hours, the clamps were removed and the gastrocnemius muscle was resected at various times up to 72 hours after reperfusion. Five specimens of the muscle were obtained at each time point from 5 rats. When any rat died during the study, additional rats were used until 5 specimens could be obtained from 5 rats at each time point. The expression of three proteins was detected by Western blot analysis. The apoptotic cells were detected using terminal deoxytransferase-mediated dUDP (deoxyuridine[ 5']diphosphate) nick-end labeling assay. Histopathological study showed severe interstitial edema and leukocyte infiltration at 6 hours of ischemia compared with 3 hours of ischemia. Moreover, at 6 hours of ischemia, muscle fiber fragmentation was observed at 72 hours after reperfusion whereas no fragmentation was found at 3 hours of ischemia. At 3 hours of ischemia, p53 and p21(WAF-1) accumulated after reperfusion, and there was a time lag in the time of onset of elevation and the peak time point between these two proteins. The level of Bax protein did not elevate and the rate of apoptotic cells did not increase. At 6 hours of ischemia, p53 and p21(WAF-1) also accumulated, but the kinetics of p21(WAF-1) were similar to that of p53 in the time of onset of elevation and the peak time point after reperfusion. In addition, the level of Bax protein increased and apoptosis was induced. These results demonstrated that p53 and p21(WAF-1) accumulated after 3 and 6 hours of ischemia of skeletal muscle during reperfusion. Moreover, it was demonstrated that the kinetics of induced p53, p21(WAF-1) and Bax protein differ between 3 hours and 6 hours of ischemia, and it is speculated that this difference plays an important role in determining the consequence of the cell exposed to ischemia. PMID- 11773734 TI - The V-Y island dorsal nasal flap for reconstruction of the nasal tip. AB - The dorsal nasal flap and its modifications have proved reliable in the coverage of defects on or adjacent to the tip of the nose. However, the problems inherent in the nature of the flap are limited rotational movement afforded by the pedicle, visible scars crossing the dorsum and the natural concavity of the alar crease, skin thickness discrepancy between the flap and the skin, and dog-ear deformity created by the rotation. The purpose of this study was to design a new modification of the dorsal nasal flap, in the highlight of a cadaveric study, that can overcome the traditional drawbacks. Ten adult human cadavers were used to study the vascular basis of the flap and to simulate application of the flap. Cadaveric dissections demonstrated that a skin island over the nasal dorsum and glabellar area can be elevated safely based on a dual axial supply (i.e., the terminal branches of the angular artery and vein bilaterally), and can be advanced easily in a V-Y manner to cover the nasal tip defect. The result obtained in the clinical case showed that the V-Y island dorsal nasal flap provided a sizable amount of skin with more appropriate texture and color for coverage of the nasal tip defect without tension or secondary deformity. PMID- 11773735 TI - An unusual complication of the treatment of a hemangioma. AB - A 3-month-old infant was administered high-dose systemic prednisolone for management of a hemangioma of the nasal sidewall. After 10 weeks of therapy, medical evaluation of weight loss disclosed hypertrophic obstructive cardiomyopathy. After discontinuation of the steroid, the cardiomyopathy resolved. PMID- 11773736 TI - Management of postpneumonectomy bronchopleural-cutaneous fistula with a single free flap. AB - A variety of local flaps have been described for chest wall and bronchopleural fistula reconstruction. When local options cannot be used because of previous surgery, trauma, radiation, or body habitus, free flaps become an acceptable option. The authors report a case of persistent bronchopleural-cutaneous fistula treated with a free latissimus dorsi musculocutaneous flap that obliterated the right chest cavity, closed the site of empyema drainage, and aided healing of a bronchopleural fistula. Surgical technique including anastomosis to the innominate vein is described. PMID- 11773737 TI - Silicone gel breast implant rupture rates: research issues. AB - Documenting the rate of rupture of silicone breast implants appears to be deceptively easy. Largely because of the phenomenon of "silent rupture," it isn't. The authors explore the various technical biases (selection, misclassification, and confounding) and methodological problems that have plagued much of the research conducted to date. By means of a series of illustrations, they argue that explantation has limited utility. Noninvasive techniques have to be used to gather the proper type of data on the timing and frequency of these events. Only with the proper incidence data will researchers be able to identify better the different mechanisms underlying implant rupture and the relative importance of each. The authors recommend that better and standardized definitions of implant rupture be developed, that greater recognition be given to the technical biases and a greater effort be made to eliminate them from investigations of implant rupture, and that more research be conducted by multidisciplinary teams. Because of the growing awareness of the complexity of this issue, the authors also recommend that properly constituted advisory teams be used to provide comprehensive oversight of future research projects from beginning to end. PMID- 11773739 TI - Reduction mammaplasty: cosmetic or reconstructive procedure? Reply. PMID- 11773740 TI - Pressure sore from a fruit seed under a hip spica cast. PMID- 11773741 TI - Calciphylaxis: cutaneous necrosis in chronic renal failure. PMID- 11773742 TI - Chest wall reconstruction. PMID- 11773743 TI - Decreased serum nitric oxide level in experimental frostbite injury: a preliminary study. PMID- 11773744 TI - Case of a rapidly growing blue-purple median raphe cyst of the penis. PMID- 11773745 TI - Abdominoplasty and seroma. PMID- 11773746 TI - Warthin's tumor of the cervical lymph node: an incidental finding. PMID- 11773747 TI - The Journal Marks the Millennium (Again!). PMID- 11773753 TI - BURN PREVENTION FORUM. PMID- 11773754 TI - NURSING FORUM. PMID- 11773756 TI - PT/OT FORUM. PMID- 11773755 TI - PSYCHOSOCIAL FORUM. PMID- 11773757 TI - BURN PREVENTION FORUM. PMID- 11773758 TI - ETHICS FORUM. PMID- 11773759 TI - NUTRITION FORUM. PMID- 11773761 TI - Physical Medicine and Rehabilitation. PMID- 11773760 TI - PSYCHOSOCIAL FORUM. PMID- 11773763 TI - NURSING FORUM. PMID- 11773762 TI - NURSING FORUM. PMID- 11773764 TI - PSYCHOSOCIAL FORUM. PMID- 11773766 TI - BURN PREVENTION FORUM. PMID- 11773765 TI - In Memoriam: Barbara Knothe, MOT, OTR/L, CHT, 1945-2001. PMID- 11773767 TI - BURN REHABILITATION FORUM. PMID- 11773768 TI - NURSING FORUM. PMID- 11773769 TI - PT/OT FORUM. PMID- 11773770 TI - The American Burn Association in the New Millennium. PMID- 11773771 TI - NUTRITION FORUM. PMID- 11773799 TI - No widespread psychological effect of the fragile X premutation in childhood: evidence from a preliminary controlled study. AB - This study was designed to examine the effect of the fragile X premutation (pM) on cognitive function and behavior. Participants included 14 children (7 males, 7 females) with the fragile X pM and 14 children without the fragile X pM (and without the fragile X full mutation [fM]), each of whom was matched by age and gender with one of the participants from the pM group. The children ranged in age from 3 years, 1 month, to 17 years, 11 months. Participants were individually administered measures of intellectual functioning, academic achievement, and visual motor integration. Parent rating scales of problem behaviors were completed. Group differences were examined using nonparametric statistics. No statistically significant differences were found between the premutation and nonpremutation groups. The results from this study are consistent with the hypothesis that the premutation does not, in general, have an effect on a child's development. However, this does not preclude cases where specific factors may lead to a specific phenotype. PMID- 11773800 TI - Psychosocial development in adolescents with Turner syndrome. AB - Turner syndrome is a genetic condition in which part or all of the second X chromosome is missing. Our goal in this study was to examine the psychosocial adjustment of a sample of adolescent girls with Turner syndrome. Subjects included 122 girls with a diagnosis of Turner syndrome (TS) and a control group of 108 girls with no genetic disorder or chronic illness. Subjects were 13 to 18 years of age. A battery of questionnaires assessing social, academic, school, and behavioral functioning was administered. TS girls were seen as having significantly more problems in terms of social relationships and school progress and were more likely to meet criteria for attention-deficit hyperactivity disorder than control girls. The TS girls were also rated by a parent as less socially competent (e.g., fewer friends, less time with friends) than the control group. Social difficulties appear to be an area of vulnerability for TS girls. Counseling individuals with Turner syndrome and their families about the need to carefully develop and nurture social skills and relationships may prove useful in advancing the social adaptation of these young women. PMID- 11773801 TI - Differential patterns of development: the interaction of birth weight, temperament, and maternal behavior. AB - A short-term longitudinal study of 83 families compared patterns of development between full-term small for gestational age (SGA) and normal birth weight (NBW) infants. Data were collected on infant temperament and maternal interaction at 3 and 6 months, and infant developmental outcomes at 6 months in order to investigate relationships between infant and maternal behavior, and developmental outcomes as a function of birth weight. Findings revealed few differences between SGA and NBW groups. However, the relations between infant temperament and maternal behavior varied as a function of birth weight and home environment. Specifically, more positive home environments were associated with higher ratings of maternal behavior and lower levels of infant negative reactivity for SGA but not for NBW infants. In addition, higher negative reactivity was related to lower performance on both the mental and psychomotor scales of the Bayley Scales of Infant Development (BSID), with stronger associations reported for SGA infants than for NBW infants. PMID- 11773802 TI - The influence of etiology and treatment factors on intellectual outcome in congenital hypothyroidism. AB - To determine the effects of hypothyroidism and hormonal patterns on outcome, we tested 65 7- to 12-year-old children with congenital hypothyroidism using standardized tests of intelligence, neuropsychological functioning, memory, and achievement. Results were analyzed by etiology, time to thyrotropin normalization, and hormone levels at testing. Children with athyreosis scored below other etiologies on visuospatial, attention, and arithmetic indices. Children whose thyroid-stimulating hormone levels normalized by 1 to 2 months of age scored higher than later normalizers on indices of visual memory, attention, and arithmetic. Normalization of thyroid-stimulating hormone by 3 months of age was associated with better memory and learning abilities than later normalization. Thyroid hormone levels at testing were correlated with indices of sensorimotor, spatial, and language abilities. Two children with persistently elevated thyrotropin levels were not adversely affected. Present findings signify the need to establish etiology, normalize thyrotropin early, and maintain hormone levels in the normal range throughout childhood in children with congenital hypothyroidism. PMID- 11773803 TI - Effects of colostrum in newborn humans: dissociation between analgesic and cardiac effects. AB - This study evaluates the effects of colostrum, delivered via syringe or on a pacifier, on the pain and heart rate reactions of newborns undergoing routine heel-lance. This was achieved by following a quasi-randomized, controlled trial in which 60 newborn infants at Boston Medical Center, Boston, MA, were randomly assigned to receive colostrum, sucrose, or water, by syringe or on a pacifier, for a total of 6 groups (n = 10 per group). The effectiveness of an intervention was determined by comparing crying, grimacing, and heart rate differences among groups during and following blood collection. We report that colostrum, delivered by syringe or on a pacifier, did not reduce crying or grimacing relative to control infants who received water. As has been previously reported, sucrose markedly reduced both crying and grimacing, and attenuated the rise in heart rate that normally accompanies blood collection (p < .002). Water, via syringe or on a pacifier, did not prevent the increase in heart rate, nor did colostrum via syringe. In contrast, colostrum delivered on a pacifier prevented the increase in heart rate despite pain reactivity and extreme crying. The implications of this dissociation are discussed. PMID- 11773804 TI - Maternal feeding practices and beliefs and their relationships to overweight in early childhood. AB - To better explore possible factors that may lead to childhood obesity, we developed and analyzed two new instruments that assess maternal feeding practices and beliefs. The Infant Feeding Questionnaire (IFQ) assesses feeding during the entire first year of life and was administered to 453 mothers of children 11 to 23 months old. The Preschooler Feeding Questionnaire (PFQ) assesses feeding of young children between the ages of 2 to 5 years and was administered to 634 mothers of children this age. Each questionnaire was factor analyzed and mean factor scores were calculated and linked with the children's measured and mothers' self-reported weight and height. Mean factor scores from the IFQ and PFQ were compared between mothers who were obese (body mass index > or = 30 kg/m2) and those who were nonobese, between those who did and those who did not have an overweight child (weight-for-height > or = 90th percentile), and between those who had a low income (< or = 185% of the poverty level) and those who had a high income. To control for confounding variables and to detect interaction among variables, hierarchical linear regression was used. Results from this study did not suggest that there is a particular "feeding style" that is associated with overweight in young children; however, there were differences found in feeding behaviors between high and low income mothers. PMID- 11773805 TI - The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. AB - This study was designed to explore the behavioral phenotype of autism in a group of young children with fragile X syndrome (FXS). Twenty-four children with FXS, ages 21 to 48 months, were compared with two well-matched groups: 27 children with autism (AD) and 23 children with other developmental delays (DD), on two standardized autism instruments, as well as on measures of development and adaptive behavior. Two FXS subgroups emerged. One subgroup (n = 16) did not meet study criteria for autism. Their profiles on the autism instruments and the developmental instruments were virtually identical to the other DD group. The other FXS subgroup (n = 8, or 33% of the total FXS group) met study criteria for autism. Their profiles on the autism instruments were virtually identical to the group with autism. The finding of two FXS subgroups raises a hypothesis of additional genetic influences in the FXS autism group, warranting further genetic studies. PMID- 11773806 TI - Learning about pain in preterm newborns. AB - The first goal of the study was to explore whether preterm newborns can learn to predict painful stimulation. The second goal was to provide a description of physiological and behavioral responses to repeated heel-sticks over days. Preterm newborns, born between 28 and 32 weeks gestational age, were observed five times over a period of 2 weeks while undergoing heel-sticks. Infants' facial expressions, cardiac reactions, and movement durations were recorded before, during, and after the heel-stick procedure. On Tests 1, 3, and 5, the phlebotomist picked up the baby's leg and held it for 10 seconds before proceeding to the heel-stick. Infants showed significantly greater increase in heart rate during the leg pickup on Test 5 compared with Test 1. This increase in heart rate after 2 weeks of experience suggests that newborn infants learned to anticipate the painful stimulus. Infants also demonstrated reliable behavioral and cardiac reactions to the invasive part of the heel-stick, but no change was observed in reactivity over days. However, greater post-conceptional age (PCA) was associated with increased behavioral reactivity during heel-stick on Tests 4 and 5. The anticipatory heart rate increase during leg pickup highlights the preterm infant's early capacity to learn and react to experience in the neonatal intensive care unit. The lack of global change in reactivity to the invasive procedure over days illustrates the need to take into account specific factors such as PCA when investigating sensitivity to repeated pain experiences. PMID- 11773807 TI - Preparing a 3 year old and his parents for an elective surgery. PMID- 11773808 TI - Behavioral adjustment in children with asthma: a meta-analysis. AB - This study is a meta-analytic review of the behavioral adjustment of children and adolescents with asthma. Of 78 studies initially reviewed, 26 studies (encompassing 28 data sets), reflecting data on nearly 5,000 children with asthma (mean age = 8.4 years; 40% female), met criteria for inclusion. Effect size estimates were calculated across studies using standard methods. Separate effect sizes were calculated for internalizing and externalizing behavioral problems, degrees of asthma severity, and differences in control group used (i.e., sample controls or normative data). Results indicate that children with asthma have more behavioral difficulties than do healthy children, with the effect for internalizing behaviors being greater than that for externalizing behaviors (d(mn) = .73 vs .40). Increased asthma severity was associated with greater behavioral difficulties. Results did not differ by comparison group (healthy controls vs normative data). The findings suggest that patients with asthma, particularly children with severe asthma, should be considered at higher risk for behavioral difficulties that may necessitate psychosocial intervention. PMID- 11773815 TI - Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery. AB - This study evaluates the efficacy and side effects of a low dose of epidural morphine combined with clonidine for postoperative pain relief after lumbar disc surgery. In 36 of 51 patients who accepted the procedure, an epidural catheter was inserted (L1-L2 level). General anesthesia was induced with propofol and sufentanil, and maintained with sevoflurane in O2/N2O. After emergence from anesthesia, epidural analgesia was initiated according to two randomly assigned protocols: 1 mg of morphine with 75 microg of clonidine (Group M) or 12.5 mg of bupivacaine with 75 microg of clonidine (Group B), in 10 mL saline. Piritramide was administered during the first postoperative 24 hours using a patient controlled analgesia device (PCA). The following parameters were recorded: piritramide consumption during the first 24 hours; pain at rest during the first postoperative hours (D0), during the first night (D1), and during the first mobilization; [visual analogue scale (VAS)]; and the occurrence of drowsiness, motor blockade, respiratory depression, nausea, vomiting, itching, micturition problems, and bladder catheterization during D0 and D1. Epidural administration of morphine-clonidine significantly improved postoperative pain relief and reduced piritramide consumption as compared to epidural bupivacaine-clonidine. Side effects did not differ between groups except for a higher incidence of micturition problems in Group M during D1. The occurrence of bladder catheterization was not significantly higher in that group. We conclude that a low dose of epidural morphine combined with clonidine offers a better postoperative analgesia than does bupivacaine-clonidine. The excellent analgesic conditions were obtained at the expense of a higher incidence of difficulties in initiating micturition. PMID- 11773816 TI - Bispectral Index (BIS) may not predict awareness reaction to intubation in surgical patients. AB - Bispectral Index (BIS) has been marketed as a measure of the hypnotic component of anesthesia and is recommended as a guide for the administration of hypnotic drugs during anesthesia. BIS values between 40 and 60 are recommended for surgery under general anesthesia. This study investigates whether a BIS baseline between 50 and 60 prevents awareness reaction to endotracheal intubation. After approval by the university's Ethics Committee, 20 consenting patients were enrolled in the study. Midazolam (0.1 mg/kg PO) was given 30 minutes before induction. Anesthesia was induced with alfentanil (10 mcg/kg, followed by 2 mcg/kg(-1) x min(-1)) and propofol infusion was adjusted to a BIS target level between 50 and 60. Propofol infusion rate was maintained constant for 5 minutes with constant BIS. Prior to intubation, patients were tested in one-minute intervals for awareness using Tunstall's isolated forearm technique. Three minutes after endotracheal intubation, the study period ended and surgery was performed. After intubation, 8 of 20 patients showed an awareness reaction, squeezing the investigator's hand in response to a command. No patient had recall. Comparison of patients with and without awareness reaction revealed no differences in BIS before or after intubation. This study shows that a BIS value between 50 and 60 prior to intubation is inadequate to prevent an awareness reaction to endotracheal intubation during propofol/alfentanil anesthesia. Because BIS cannot differentiate between patients with and without awareness reaction, its value as a monitor for awareness and a measurement of the hypnotic component of anesthesia must be questioned. PMID- 11773817 TI - Effects of desflurane on jugular bulb gases and pressure in neurosurgical patients. AB - The purpose of this study was to investigate the effect of different concentrations of desflurane on jugular bulb gases and jugular bulb pressure (JBP) and to determine an optimal concentration of desflurane in neurosurgical patients with supratentorial tumor. Twenty-two patients were anesthetized with desflurane in oxygen. Radial arterial and jugular bulb catheters were inserted for blood gas sampling and direct blood pressure measurement after anesthesia. Mean arterial blood pressure (MAP), heart rate (HR), and JBP were monitored continuously. Arterial and jugular bulb blood gases were measured at 0.7 minimum alveolar contraction (MAC) (4.2%), 1.0 MAC (6%), and 1.3 MAC (7.8%) of desflurane randomly after a 30-minute stabilization period, respectively. Jugular bulb oxygen saturation (S(J)O2) significantly increased and cerebral arteriojugular difference of oxygen content (A(J)DO2) and oxygen extraction ratio (O2ER) significantly decreased from 0.7 MAC to 1.0 MAC of desflurane, but there was no further increase in S(J)O2 nor further decreases in A(J)DO2 and O2ER at 1.3 MAC compared with 1.0 MAC desflurane. There was a significant dose-related decrease in MAP from 0.7 MAC to 1.3 MAC of desflurane, but JBP did not change significantly. No significant change in hour was observed in the study. It is concluded that 1.0 MAC is a suitable concentration of desflurane in neurosurgery with an improved balance between cerebral oxygen supply and demand. PMID- 11773819 TI - Treatment of transtentorial herniation unresponsive to hyperventilation using hypertonic saline in dogs: effect on cerebral blood flow and metabolism. AB - We tested the hypothesis that transtentorial herniation (TTH) represents a state of cerebral ischemia that can be reversed by hypertonic saline. Because of the high mortality associated with TTH, new therapeutic strategies need to be developed for rapid and effective reversal of this process. We produced TTH (defined by acute dilatation of one or both pupils) by creating supratentorial intracerebral hemorrhage with autologous blood injection in seven mongrel dogs anesthetized using intravenous pentobarbital and fentanyl. We measured serial rCBF (regional cerebral blood flow) using radiolabeled microspheres in regions around and distant to the hematoma. Cerebral oxygen extraction and oxygen consumption (CMRO2) were measured by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were continuously monitored. TTH was successfully reversed over a mean period of 25.7 +/- 4.9 minutes after intravenous administration of 23.4% sodium chloride (1.4 mL/kg) in all animals. All measurements were recorded 15, 30, 60, and 90 minutes after administration of 23.4% sodium chloride. Compared to prehematoma ICP (14.1 +/- 1.7 mm Hg, mean +/- SE), elevation in ICP was observed during TTH (36.2 +/- 7.2 mm Hg) with no change in cerebral perfusion pressure (CPP) (80.4 +/- 4.7 vs. 76.7 +/- 10.1 mm Hg) because of concomitant elevation in mean arterial pressure. Compared to baseline values, there was a reduction in rCBF (mL/100 gm/min +/- SE) in brainstem (12.1 +/- 2.0 vs. 21.4 +/- 1.4), gray matter (18.2 +/- 2.1 vs. 31.4 +/- 1.8), and white matter (8.6 +/- 1.7 vs.18.7 +/- 0.9) in the hemisphere contralateral to the hematoma; and gray matter (12.9 +/- 2.9 vs. 27.9 +/- 2.2) and white matter (8.3 +/- 2.0 vs.19.9 +/- 1.0) in the ipsilateral hemisphere distant from the hematoma. Administration of 23.4% sodium chloride resulted in reduced ICP at 15 minutes (12.7 +/- 1.4) and 30 minutes (15.6 +/- 3.1) after administration. RCBF values were restored in all regions studied after administration of 23.4% sodium chloride with an increase in CMRO2 (1.8 +/- 0.4 vs. 3.9 +/- 0.7 mL O2 /100 gm/min). Compared with baseline values, rCBF increased in the ipsilateral (31.7 +/- 2.5 vs. 63.4 +/- 11.7) and contralateral (28.7 +/- 1.9 vs. 45.5 +/- 5.7) thalamus at 15 minutes after administration of 23.4% sodium chloride. TTH represented a state of ischemia in brainstem and supratentorial gray and white matter in the presence of adequate CPP, suggesting mechanical compression of vessels at the level of tentorium. Hypertonic saline reversed TTH, and restored both rCBF and CMRO2, although hyperemia was observed immediately after reversal of TTH. Administration of hypertonic saline may preserve neurologic function during the interim period between TTH and surgical intervention. PMID- 11773818 TI - Reverse Trendelenburg position reduces intracranial pressure during craniotomy. AB - Cerebral swelling and herniation pose serious surgical obstacles during craniotomy for space-occupying lesions. Positioning patients head-up has been shown previously to reduce intracranial pressure (ICP) in neurotraumatized patients, but has not been investigated during intracranial surgery. The current study examined the effects of 10-deg reverse Trendelenburg position (RTP) on ICP and cerebral perfusion pressure (CPP). Forty adult patients subjected to craniotomy for supratentorial tumors were given standardized propofol-fentanyl cisatracurium general anesthesia and were moderately hyperventilated. In 26 of 40 patients with expected poor clinical outcome, an additional catheter was placed in the internal jugular bulb to determine internal jugular bulb pressure (JBP). ICP was determined by subdural measurement using a 22-gauge needle advanced through the dura after removal of the bone flap. ICP was referenced to the level of the dural incision. ICP, mean arterial blood pressure, and CPP were compared with repeat measurements 1 minute after RTP. The tension of the dura was graded qualitatively by the surgeon by digital palpation and was compared to post-RTP. ICP decreased from 9.5 mm Hg to 6.0 mm Hg ( P <.001; all values are median) within 1 minute after 10-deg RTP. Mean arterial blood pressure decreased from 82.0 mm Hg to 78.5 mm Hg ( P <.001). CPP was unchanged (70.5 mm Hg versus 71 mm Hg after RTP), whereas JBP decreased from 8 mm Hg to 4 mm Hg ( P <.001). High initial ICP was correlated to the greatest magnitude of decrease in ICP. No significant correlation was found between change in ICP and change in JBP. Intracranial pressure after RTP resulted in decreased tension of the dura. RTP appears to be an effective means of reducing ICP during craniotomy, thereby reducing the risk of cerebral herniation. CPP is not affected. Studies over longer periods of time are warranted, however. PMID- 11773820 TI - Phenylephrine increases cerebral perfusion pressure without increasing intracranial pressure in rabbits with balloon-elevated intracranial pressure. AB - Using a rabbit model of intracranial hypertension, we studied the effects of infusion of phenylephrine on intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Seven New Zealand white rabbits were anesthetized with isoflurane and normocapnia was maintained. An extradural balloon was used to raise ICP to 25 +/- 1 mm Hg. Infusion of phenylephrine increased mean arterial blood pressure (MAP) (77 +/- 6 --> 95 +/- 8 mm Hg) and CPP (52 +/- 7 --> 70 +/- 7 mm Hg). ICP was unchanged during infusion of phenylephrine (25 +/- 1 vs. 25 +/- 2 mm Hg). The phenylephrine infusion was stopped after 45 minutes and MAP returned to baseline (76 +/- 8 mm Hg). We conclude that phenylephrine increased CPP because of its effect on MAP, but did not alter ICP. Phenylephrine may be used to increase CPP without raising ICP when autoregulation is intact. PMID- 11773821 TI - Peri-ischemic aminoguanidine fails to ameliorate neurologic and histopathologic outcome after transient spinal cord ischemia. AB - Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient spinal cord ischemia. An important effect of the neuroprotective substance aminoguanidine (AG) is the inhibition of inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for spinal cord ischemia, and related these findings to the protein content of iNOS in the spinal cord. Temporary spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20; 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS protein content was determined using Western blot analysis 48 hours after ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of paraplegia was 67% in the saline treated group versus 53% in the AG-treated group. No differences in infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition after treatment with AG. PMID- 11773822 TI - Hazards of epinephrine in transsphenoidal pituitary surgery. AB - A 79-year-old woman with no history of myocardial ischemia presented with symptoms of pituitary apoplexy for which an urgent transsphenoidal resection of the pituitary gland was undertaken. The nasal passages were prepared with topical application of epinephrine followed by injection of what was presumed to be 1% lidocaine containing 10 microg/ml(-1) of epinephrine. After only 1.5 mL of the solution had been injected, she developed a hypertensive crisis, which was immediately treated. Postoperatively, she developed a myocardial infarction. The risks associated with the use of vasopressors are reviewed and suggestions for their safe use are presented. PMID- 11773823 TI - A rare complication of trigeminal nerve stimulation during radiofrequency thermocoagulation: sudden ST segment elevation. AB - Coronary vasospasm resulting from a sudden autonomic response associated with an intracranial procedure was encountered during percutaneous radiofrequency trigeminal rhizotomy. Although it is very rare, careful monitoring and readiness for the occurrence of such a potentially lethal situation with necessary medications may prevent a fatal outcome. PMID- 11773824 TI - Intracranial effects of endotracheal suctioning in the acute phase of head injury. AB - In patients with head injury, endotracheal suctioning (ETS) is a potentially dangerous procedure, because it can increase intracranial pressure (ICP). The purpose of this prospective nonrandomized study was to evaluate the impact of ETS on intracranial dynamics in the acute phase of head injury. Seventeen patients with severe head injury (Glasgow Coma Score < or = 8, range 4-8), sedated and mechanically ventilated, were studied during the first week after trauma. Single pass ETS maneuver (with a 16-French catheter, negative pressure of 100 mm Hg, and duration of less than 30 seconds) was performed 60 seconds after the FiO2 was increased to 100%. After ETS, FiO2 was maintained at 100% for another 30 seconds. Before and after ETS, arterial blood gases and jugular oxygen saturation (S(j)O2), ICP, and mean arterial pressure (MAP) were measured and cerebral perfusion pressure (CPP) was calculated. A total of 131 ETS episodes, which consisted of repeated assessment of each patient, were analyzed. Six patients in 20 cases coughed and/or moved during ETS because of inadequate sedation. After ETS, ICP increased from 20 +/- 12 to 22 +/- 13 mm Hg in well-sedated patients and from 15 +/- 9 to 28 +/- 9 mm Hg in patients who coughed and/or moved (mean change, 2 +/- 6 versus 13 +/- 6 mm Hg, P <.0001). CPP and S(j)O2 increased in well-sedated patients (from 78 +/- 16 to 83 +/- 19 mm Hg, and from 71 +/- 10 to 73 +/- 13%, respectively) and decreased in patients who reacted to ETS (from 79 +/- 14 to 72 +/- 14 mm Hg and from 69 +/- 7 to 66 +/- 9%, respectively), and the differences were significant (mean change, CPP: 5 +/- 14 versus -7 +/- 15 mm Hg, P =.003; (S(j)O2) 2 +/- 5 vs. -3 +/- 5%, P <.0001). In well-sedated patients, endotracheal suctioning caused an increase in ICP, CPP, and S j O 2 without evidence of ischemia. In contrast, in patients who coughed or moved in response to suctioning, there was a slight and significant decrease in CPP and S(j)O2. In the case of patients with head injuries who coughed or moved during endotracheal suctioning, we strongly suggest deepening the level of sedation before completing the procedure to reduce the risk of adverse effects. PMID- 11773825 TI - Sedative doses of remifentanil have minimal effect on ECoG spike activity during awake epilepsy surgery. AB - The use of remifentanil for sedation during awake epilepsy surgery has been described in a case report. However, little information is available regarding the effect of remifentanil on the quality of intraoperative electrocorticography (ECoG). This study was designed to investigate the effect of sedative doses of remifentanil on ECoG interictal spike activity among patients undergoing awake anterior temporal lobectomy for refractory epilepsy. Ten adult patients were studied prospectively. After baseline EcoG recordings were obtained, remifentanil was administered as a continuous infusion at 0.1 microg/kg/min and the ECoG recorded continuously for 15 minutes. Recordings obtained before and during the administration of remifentanil were compared with respect to spike frequency and location. A trend toward a small decrease in spike frequency was observed as patients became increasingly somnolescent and background ECoG activity slowed. The difference was not statistically significant. Blood pressure and heart rate were not adversely affected by the administration of remifentanil. Respiratory rates decreased in all patients (mean decrease, 8 breaths/min) and one patient transiently developed a respiratory rate of 4 breaths per minute that elicited a decrease in the rate of remifentanil administration. Remifentanil administered at sedation doses does not adversely affect intraoperatively recorded interictal spike activity. Further investigation of the use of this drug during awake epilepsy surgery is warranted. PMID- 11773826 TI - Effects of sevoflurane on electrocorticography in patients with intractable temporal lobe epilepsy. AB - Fentanyl-droperidol technique is the choice for epilepsy surgery. It requires intraoperative electrocorticography (ECoG), but a large dose of fentanyl is needed for this technique. On the other hand, sevoflurane reportedly may be beneficial for intraoperative ECoG. To reveal whether the combined technique with fentanyl and sevoflurane is beneficial for epilepsy surgery, we investigated ECoG in 10 patients with intractable temporal lobe epilepsy without sevoflurane, with 0.5 minimum alveolar concentration (MAC) sevoflurane, and with 1.5 MAC sevoflurane under fentanyl-based anesthesia. The mean number of spikes for 1 minute decreased from 38.3 to 14.1 after 1.5 MAC sevoflurane was induced, which was statistically significant ( P <.05). Our results showed that balanced technique with neurolepto-analgesia (NLA) and sevoflurane is not suitable for epilepsy surgery requiring intraoperative ECoG. When epilepsy surgeries are performed under sevoflurane anesthesia, it is important to consider that sevoflurane may suppress electric activities when it is used with other anesthetic agents. PMID- 11773827 TI - Effect of sevoflurane on electrocorticogram in normal brain. AB - To clarify the epileptogenicity of sevoflurane, electrocorticograms were monitored in seven patients with unruptured cerebral aneurysm under sevoflurane anesthesia. They had no history of epilepsy or other complications. Spike activities on electrocorticography were seen in all seven patients at 3.3% end tidal sevoflurane. These results suggest that further study is required to evaluate the suitability of sevoflurane for neurosurgical procedures. PMID- 11773828 TI - Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. AB - Oxygen-centered free radicals cause brain injury associated with trauma and stroke. These reactive oxygen species may be detoxified by endogenous antioxidants, but cell death occurs after antioxidants become depleted. General anesthetics penetrate into brain parenchyma, where they may abrogate oxidative injury to neurons by several mechanisms that prevent the initiation of free radical chain reactions or terminate the propagation of highly reactive radicals. First, general anesthetics may inhibit free radical generation because these drugs slow cerebral utilization of oxygen and glucose, inhibit oxidative metabolism in neutrophils, and prevent redox changes in hemoglobin. Second, antioxidant anesthetics, such as thiopental and propofol, directly scavenge reactive oxygen species and inhibit lipid peroxidation. Finally, anesthetics may prevent the elevation of extracellular glutamate concentration and inhibit the activation of excitatory glutamatergic receptors that augment oxidative stress after ischemia. PMID- 11773829 TI - Collaborative practice--balancing the future. PMID- 11773830 TI - Respiratory complications of pregnancy. AB - The pregnant woman is susceptible to a variety of respiratory complications. When a pregnant patient presents with an abnormal chest x-ray or a pulmonary complaint, an understanding of the pathophysiology of pregnancy will guide the clinician in establishing a diagnosis. Pregnancy brings about many changes to a woman's body. One of the more intriguing is a decrease in the T helper cells, resulting in a state of relative immunosuppression. Despite this, the prevalence of infectious pneumonia is not increased in pregnancy. Complications from pneumonia, however, are increased in the pregnant host. Most notably are increases in both mortality related to influenza infection and the risk for dissemination of coccidioidomycosis. Other physiologic changes predispose the pregnant woman to certain disease processes. Hypercoagulability associated with pregnancy results in a marked increase in the incidence of thromboembolic disease. Although rare, pregnancy is also associated with other embolic phenomena including amniotic fluid embolism, air embolism, and trophoblastic embolism. Because of the increases in intravascular volume and cardiac output that occur in pregnancy, women with underlying structural heart disease will frequently present for the first time or have an exacerbation of their disease. This is especially true of mitral stenosis. Peripartum cardiomyopathy also can occur, and for the majority of patients, the heart remains damaged for life. Finally, although uncommon, lymphangioleiomyomatosis will often present or become exacerbated during pregnancy. Patients with this disorder need to be counseled concerning the increased risk associated with pregnancy. This paper reviews the various respiratory complications associated with pregnancy. PMID- 11773831 TI - Intrahepatic cholestasis of pregnancy: review of the literature. AB - Intrahepatic cholestasis of pregnancy (ICP) is a rare disorder of unknown etiology with a symptomatically distressing maternal course with pruritus as the chief complaint. ICP poses little medical risk to the mother, but poses significant risk to the fetus of perinatal mortality, preterm delivery, fetal distress, and meconium staining. ICP has a geographically variable prevalence and appears to have a heritable component. Current evidence suggests a susceptibility to derangements in the sulfation of steroid compounds, affecting the metabolism of progesterone and bile acids in the fetal/placental compartment. This impairs transport of bile acids across the placenta from the fetal to the maternal circulation. Exactly how this leads to fetal compromise is unknown. The most efficacious current medical management that improves both maternal symptoms and laboratory abnormalities is ursodeoxycholic acid (UDCA), a hydrophilic bile acid that alters the composition of the bile acid pool in maternal blood. When ICP is diagnosed, UDCA coupled with close maternal-fetal surveillance is indicated. Delivery should be effected near term, with confirmation of fetal lung maturity or earlier if fetal compromise is identified. PMID- 11773832 TI - Diagnosis and management of clostridium perfringens sepsis and uterine gas gangrene. AB - The progression of Clostridium perfringens endomyometritis to gas gangrene is a rare, but greatly feared complication in the obstetrical patient. While endometritis following cesarean delivery is a common complication, recognition of C. perfringens as the pathogen as well as its progression to gas formation in the myometrium is essential to the survival of the patient. We present a patient that we recently cared for, and review the bacteriology, clinical diagnosis, and management. PMID- 11773833 TI - So Far, So Fun: Reflections After Two Years of Editing OPRS. PMID- 11773834 TI - In Memoriam: Leo Koornneef. PMID- 11773835 TI - Progress in the prevention of otitis media through immunization. AB - OBJECTIVE: To review the progress that has been made in developing effective vaccines against the major bacterial pathogens responsible for acute otitis media. DATA SOURCE: Review of the literature with the aid of the MEDLINE database using the search terms otitis media and otitis media and vaccine. DATA EXTRACTION: Data were collected from clinical trials and laboratory studies. FINDINGS: The heptavalent pneumococcal conjugated vaccine, Prevnar, reduced the incidence of acute otitis media from all causes by 7% in one study and by 6% in another study. For culture-positive pneumococcal otitis media, the point estimate of efficacy was 66.7% in one study, and the reduction in incidence was 34% in another study. A Phase I clinical trial has been completed successfully for a conjugated vaccine against nontypeable Haemophilus influenzae (NTHi), which has high immunogenicity for mice and rabbits, induces complement-mediated bactericidal activity against NTHi in rabbits, and is protective against NTHi otitis media in chinchillas. A conjugated vaccine against Moraxella catarrhalis elicits strong immune responses in mice and rabbits and induces complement mediated bactericidal activity in rabbits. CONCLUSION: The prevention of otitis media is likely to require multivalent pneumococcal, NTHi, and M. catarrhalis vaccines, and these vaccines likely can be developed within a decade. PMID- 11773836 TI - Intranasal metered dose aerosolized surfactant reduces passive opening pressure of the eustachian tube: comparison study in two animal models. AB - HYPOTHESIS: Intranasal metered dose aerosolized inhaler surfactant will reduce opening pressure of the eustachian tube in gerbils and mice. BACKGROUND: Eustachian tube opening pressure necessary to allow ventilation of the middle ear must exceed the contractile force exerted by the tension on the curved surface of the eustachian tube. When the active function of opening the eustachian tube is inefficient, functional collapse of the tube persists, resulting in negative middle ear pressure. Such dysfunction is the primary cause of otitis media with effusion in children. METHODS: Surfactant in a metered dose aerosolized intranasal delivery system was administered to 61 healthy Mongolian gerbils and 34 albino mice. In the first arm of the experiment, measurements of eustachian tube passive opening pressure were taken at baseline, after the delivery of propellant, and then at 5 and 10 minutes after surfactant administration. In the second arm of the experiment, the animals were divided into control, propellant, and experiment groups. At zero minutes, propellant was administered to the propellant group and intranasal surfactant was administered to the experiment group. Measurements of eustachian tube passive opening pressure were taken at 0, 5, and 10 minutes. RESULTS: Surfactant administration in the gerbil reduced eustachian tube passive opening pressure from a basal measurement of 40.5 mm Hg to 32.5 mm Hg after 5 minutes and to 30.1 mm Hg after 10 minutes. In mice, eustachian tube passive opening pressure reduced from a basal level of 41.8 mm Hg to 31.3 mm Hg after 5 minutes and to 31.2 mm Hg after 10 minutes in the surfactant group. Propellant placebo resulted in no change from basal level in both animal models and in both arms of the experiment. CONCLUSION: Intranasal metered dose inhaler aerosolized surfactant is effective in reducing eustachian tube passive opening pressure. PMID- 11773837 TI - Management of anterior epitympanic cholesteatoma: expectations after epitympanic approach and canal wall reconstruction. AB - BACKGROUND: The epitympanic approach to cholesteatoma provides excellent access to the anterior epitympanic space. When it is combined with reconstruction of the scutum, it is tempting to propose that the approach may offer the patient the advantage of both canal wall up and canal wall down techniques and the disadvantages of neither. In theory, then, the incidence of residual/recurrent cholesteatoma should be no greater than that for canal wall down surgery, and the need for a second look often associated with the canal wall up procedure should be less compelling. However, validation of this theory is lacking. OBJECTIVE: To test this theory, we sought to establish the incidence of recidivism in patients undergoing cholesteatoma removal via the epitympanic approach followed by canal wall reconstruction, to identify anatomic factors predisposing to persistent disease, and to identify technical features or problems associated with recurrent cholesteatoma. STUDY DESIGN: A retrospective case series. SETTING: A tertiary referral center. PATIENTS: Fifty-four adults and 11 children with extensive cholesteatoma involving but not limited to the anterior epitympanic space. INTERVENTION: All patents underwent removal of cholesteatoma via the epitympanic approach with canal wall reconstruction followed by reexploration 1 year later. RESULTS: Recurrent/residual disease was observed in 6 adults (11%) and 5 of 11 children (45%). The anterior epitympanic space harbored cholesteatoma in 100% of adults and 80% of children with recurrent disease. CONCLUSION: The epitympanic approach does not eliminate the need for reexploration in cases of extensive cholesteatoma involving the anterior epitympanic space. The anterior epitympanic space is highly likely to harbor residual disease. Features of the canal wall reconstruction can be identified that predispose to recurrence. Long-term follow up and close surveillance are mandatory, especially in children. PMID- 11773838 TI - Posterior and attic wall osteoplasty: hearing results and recurrence rates in cholesteatoma. AB - OBJECTIVE: To assess the efficacy of a surgical technique, the temporary attic and posterior canal wall osteoplasty, in preventing cholesteatoma recurrence. DESIGN/PARTICIPANTS: The records of 94 patients submitted to tympanoplasty for cholesteatoma in the ear, nose, and throat department of a main city hospital between 1989 and 1997 were retrospectively reviewed. INTERVENTIONS: Intact canal wall procedure with attic and posterior canal wall temporary removal was performed in 47 cases. A canal wall down operation was performed in the 47 remaining cases. The follow-up ranged from 22 to 84 months. METHODS AND MAIN OUTCOME MEASURES: The patients from one group could be exactly matched for the main prognostic factors (type of cholesteatoma, ossicular status, and preoperative auditory status) with the patients from the other group. Auditory results were defined according to the Committee on Hearing and Equilibrium Guidelines. A 1-way analysis of variance was used to determine group differences. A probability value of p < 0.05 was the level of significance selected. RESULTS: All of the patients in the 2 groups were cholesteatoma free at the last follow up, and significantly better hearing results were observed in the osteoplasty group. CONCLUSIONS: The osteoplasty with temporary removal of the posterior and attic canal wall is a useful adjunct to tympanoplasty in cholesteatoma cases as far as the hearing results and recurrence rates are concerned. This method combines the functional advantages of canal wall up operations with the safety yielded by canal wall down procedures. PMID- 11773839 TI - Preoperative topical ofloxacin solution for tympanoplasty: a randomized, controlled study. AB - OBJECTIVE: To establish the efficacy of immediate preoperative ototopical ofloxacin eardrops in eradicating middle ear pathogens and improving operative outcome. STUDY DESIGN: Single-blind, randomized control study. SETTING: Tertiary referral center, ambulatory clinic, and hospital setting. PATIENTS: Consecutive patients with chronic suppurative otitis media for Type I tympanoplasty (myringoplasty). INTERVENTIONS: The patients were randomly assigned to 3 groups: Group A underwent 10-minute daily treatments with eardrops for 2 weeks before surgery, Group B underwent 3-minute daily treatments for 2 weeks before surgery, and Group C underwent no treatment. MAIN OUTCOME MEASURES: Preoperative and perioperative bacteriology and success of the surgery as defined by an intact tympanic membrane in the eighth week postsurgery. RESULTS: There were 101 patients entered in the study. The preoperative, perioperative, and postoperative observation of discharge and quantity of the discharge were compared, and no differences were found among the groups (Kruskal-Wallis test). The perioperative culture results were analyzed and 18/21 (86%) became culture negative in Group A, 23/27 (85%) became culture negative in Group B, and 3/21 (14%) became culture negative in the control group (Group C versus Group A or Group B, chi(2) tests p < 0.001). The success rates of surgery as defined by an intact tympanic membrane showed no difference: 28/33 (85%), 27/33 (82%), and 31/35 (89%) in Groups A, B, and C, respectively. The preoperative positive bacteriology rate in the surgical failures was 10/15 (67%), compared with 16/76 (21%) for the successful procedures (p < 0.001). CONCLUSION: Our study has shown that ofloxacin successfully eradicates most bacterial flora preoperatively. We cannot, however, confirm the benefits of its preoperative usage in improving the graft success rate. PMID- 11773840 TI - Safety of the erbium:yttrium-aluminum-garnet laser in stapes surgery in otosclerosis. AB - OBJECTIVE: The purpose of this study was to present early and late bone conduction hearing thresholds and data about cochlear and vestibular disturbances in patients after erbium:yttrium-aluminum-garnet (Er:YAG) laser stapedotomy in otosclerosis. STUDY DESIGN: The study design was a retrospective study. SETTING: The study was conducted at an academic tertiary referral center. PATIENTS: In this study, audiologic data of 117 patients undergoing Er:YAG laser-assisted stapedotomy for otosclerosis between 1993 and 1999 were included. MAIN OUTCOME MEASURES: The preoperative minus 2 postoperative (early, 1-3 days; late, at least 6 weeks) average pure-tone bone-conduction thresholds at 1, 2, and 4 kHz and 0.5, 1, 2, and 3 kHz were calculated. The postoperative appearance of nystagmus, vertigo, and tinnitus was analyzed. RESULTS: A total of 91 of 117 patients showed unchanged preoperative minus postoperative pure-tone bone-conduction averages at 1, 2, and 4 kHz in the late postoperative measurement. A slight deterioration was observed in 8 of 117 patients. Regarding the frequencies 0.5, 1, 2, and 3 kHz, 97 of 117 patients showed unchanged preoperative minus postoperative pure-tone bone conduction averages. A new transient tinnitus appeared in 37 of 117 patients, and a new persistent tinnitus was found in 3 of 117 patients. Most of the patients had no postoperative dizziness (63/117 patients) and no postoperative nystagmus (109/117 patients). CONCLUSION: The study did not show significant sensorineural hearing loss at or below 3 kHz. Vestibular and cochlear function has no clinically relevant suppression after Er:YAG laser stapedotomy. PMID- 11773841 TI - Prevention of postoperative meatal stenosis with anteriorly and inferiorly based periosteal flaps in congenital aural atresia surgery. AB - OBJECTIVE: The objective of this study was to evaluate postoperative meatal stenosis after surgery for congenital aural atresia using anteriorly and inferiorly based periosteal flaps (AIPFs). These were compared with the groups that did not use these flaps. STUDY DESIGN: This was a retrospective clinical study. SETTING: The study was conducted at the tertiary referral hospital. PATIENTS: There were 133 patients (151 ears) who had undergone surgical correction for congenital aural atresia from November 1987 to March 1999. INTERVENTION: The anterior approach surgical method was used to correct the congenital aural atresia. MAIN OUTCOME MEASURE: A comparison between the 2 groups, 1 using the AIPFs and the other that did not use the AIPFs, was performed to evaluate both the incidence and the interval of postoperative meatal stenosis. The correlation between the age of the first operation to correct congenital aural atresia and the incidence of postoperative meatal stenosis was also investigated. RESULTS: Meatal stenosis was the most common postoperative complication (23.8%) found. The incidence of meatal stenosis was much lower in the group using AIPFs (n = 105) than in the group that did not (n = 46) (19.0% versus 35.0%). The interval for the development of postoperative meatal stenosis showed similar distribution in both groups. In age distribution, the younger the age of the first operation, the more frequent the occurrence of postoperative meatal stenosis. CONCLUSION: AIPF is an effective surgical method for reducing the incidence of postoperative meatal stenosis. PMID- 11773842 TI - An animal model for assessment of amniotic fluid clearance from the middle ear. AB - HYPOTHESIS: To determine the time needed for clearance of amniotic fluid from the middle ear after birth, an animal model study was performed. BACKGROUND: Before birth, the middle ear is full of amniotic fluid, and there is controversy about the time it takes for it to clear postnatally. This is of importance because it is suspected that amniotic fluid in the middle ear of the newborn may affect results of screening of hearing when using otoacoustic emissions. METHODS: Adult and neonatal guinea pigs underwent a right-side cochleotomy followed by baseline otoscopy, tympanometry, and auditory nerve- and brainstem-evoked response (ABR) measurements of the left ear. Subsequently, the animals' left middle ears were filled with saline through a hole drilled in the bulla. Over the next few days, assessment of saline clearance was conducted by repeated left-side otoscopy, tympanometry, and measurement of ABR. RESULTS: After filling the middle ear with saline, the tympanic membrane was opaque, a type B tympanogram was obtained, and the ABR threshold was elevated. After an average of 6.3 +/- 3.0 days, air bubbles were seen in otoscopy, a type C tympanogram was obtained, and the ABR threshold improved. Finally, after an average of 9.5 +/- 2.7 days, all 3 parameters returned to their baseline values. CONCLUSION: Taking into consideration that this is an animal study, the results suggest that clearance of amniotic fluid from the newborn middle ear takes longer than has been generally thought. In addition, an animal model for assessing the clearance of fluid from the middle ear has been developed. PMID- 11773843 TI - Cochleosaccular pathology after perinatal and postnatal asphyxia: histopathologic findings. AB - OBJECTIVE: This study describes the histopathologic findings of a patient with severe bilateral sensorineural hearing loss after perinatal and postnatal hypoxia and asphyxia. STUDY DESIGN: Histopathologic examination on the temporal bones. SETTING: The study was performed at the Elizabeth McCullough Knowles Otopathology Laboratory, Division of Otopathology, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. RESULTS: Histopathologic examination on the left temporal bone revealed severe atrophy of the organ of Corti throughout the entire cochlea, decrease in the number of the spiral ganglion cells especially in the basal turn, and mild atrophy of saccular macula. In the right temporal bone, similar abnormalities were observed in the inner ear, but the changes were milder than those in the left temporal bone. No other distinct pathologic finding was observed in either ear. CONCLUSION: These findings suggest that the presence of severe hypoxic ischemia causes cochleosaccular atrophy. To our knowledge, this is the first histopathologic case report describing the long-term effect of perinatal and postnatal hypoxia and asphyxia that produced cochleosaccular abnormalities in the human inner ear. PMID- 11773844 TI - Anteroposterior approach with split ear canal for cochlear implantation in severe malformations. AB - OBJECTIVE: To present an anteroposterior approach with split ear canal technique in severe malformed ears in which cochlear implantation is not possible through the standard facial recess approach. SETTING: The operation was performed at Hacettepe University Medical Faculty, which is a tertiary care center. STUDY DESIGN: Case report. PATIENT: A 4-year-old female patient with severe Mondini malformation whose facial nerve was completely dehiscent and overlying the stapes and round window. INTERVENTION: The anteroposterior approach was used, and the middle ear was entered after the tympanomeatal flap was elevated. The posterior wall of the ear canal was split longitudinally with a diamond drill. The electrode was inserted easily through the ear canal and then transferred into the mastoid. CONCLUSION: The anteroposterior approach with split ear canal method may be used if, during facial recess, the landmarks in the middle ear (stapes, stapedius tendon, round window, and promontory) cannot be identified clearly because of an abnormal facial nerve (coursing anteriorly, preventing the use of a drill). It is an alternative for the canal wall down procedure. PMID- 11773845 TI - Variations in gains in auditory performance from pediatric cochlear implantation. AB - OBJECTIVE: To investigate variations in gains in auditory performance in children with cochlear implants. STUDY DESIGN: The auditory performance of 98 children was measured with the Category of Auditory Performance survey instrument. All data were collected prospectively. Variables used to explain gain in Category of Auditory Performance were age at implantation, sex, the duration of "untreated" deafness, the year in which implantation occurred, health care inputs, and cause of hearing impairment. The data were analyzed by ordered probabilistic regression analysis. RESULTS: Gain in Category of Auditory Performance was observed to be negatively related to age at implantation, the year in which implantation took place, and the number of medical consultations the child received. None of the other variables were significant determinants of gain in Category of Auditory Performance. CONCLUSION: This study demonstrates the value of examining incremental gain from implantation rather than simply examining outcome levels. It was found that pediatric implantation is subject to diminishing returns. This suggests that further relaxation of entry criteria to implant programs should be undertaken only after careful consideration. The study also confirmed that age at implantation is an important determinant of outcomes. Greater gain in Category of Auditory Performance was experienced by those who underwent implantation at a younger age. This finding has implications for screening, as well as for purchasers and providers of implant services, highlighting the importance of responding in a timely fashion to identified need. PMID- 11773846 TI - Nondestructive three-dimensional analysis of electrode to modiolus proximity. AB - PURPOSE: To propose a nondestructive method for three-dimensional analysis of inner ear morphology after cochlear implantation for isolated petrous bones. MATERIALS AND METHODS: After implantation of cochlear implant electrode arrays, fresh temporal bones were investigated on a new C-arm-based radiographic device permitting the generation of cross-sectional images and of three-dimensional models from multiple two-dimensional radiographic images taken under different projections (cone-beam computed tomography). Cross-sectional images and multiplanar reformations with a slice thickness of 0.15 mm were acquired. The relationship of the electrode to the modiolus was analyzed (distance between electrode and the modiolus; position of the electrode inside the tympanic or vestibular scale). Histologic preparation was used as a gold standard. RESULTS: In all cases, cone-beam computed tomography gave similar information concerning the position of the electrode compared with histologic analysis (tympanic scale versus vestibular scale, proximity versus distance to the modiolus). Perforation of the electrode from the tympanic to the vestibular scale could be assessed three-dimensionally in the cross-sectional images. In contrast to histology, cross-sectional imaging based on radiography is performed in less than 10 minutes and needs no preparation of the object. Because it is nondestructive, it can be repeated and used as a control after position-correcting maneuvers. CONCLUSION: Cross-sectional imaging based on radiography is a valuable tool for the analysis of the electrode-modiolus relationship after cochlear implantation in isolated temporal bones, which may confirm histologic analysis. PMID- 11773847 TI - Cochlear implantation in chronic suppurative otitis media. AB - OBJECTIVE: To evaluate management options for cochlear implantation in patients with chronic suppurative otitis media. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center with a large cochlear implant program. PATIENTS: Ten patients with chronic suppurative otitis media who received cochlear implants were identified. Case history, etiology of hearing loss, and management of the ear with the implant were evaluated. INTERVENTIONS: Cochlear implantation and subsequent rehabilitation. MAIN OUTCOME MEASURES: Early and late complications were evaluated. RESULTS: No early or late complications were identified in this group of patients after an average follow-up period of about 4 years. CONCLUSION: Cochlear implantation can be safely achieved in patients with chronic suppurative otitis media. There are several options for the management of these patients, and the approach chosen should be individualized on the basis of clinical findings. PMID- 11773848 TI - Results of the MXM Digisonic auditory brainstem implant clinical trials in Europe. AB - OBJECTIVE: To assess the potential benefit of the MXM auditory brainstem implant for patients with neurofibromatosis type 2. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral centers. PATIENTS: Fourteen patients with neurofibromatosis type 2 and bilateral acoustic neuromas underwent implantation with the MXM auditory brainstem implant during surgery to remove the second-side tumor. RESULTS: There were no complications related to the auditory brainstem implantation. Auditory sensations were present for 12 of 14 patients (86%). Global results indicated an improved quality of life for the patients receiving auditory sensations, in part because of their auditory orientation within the environment. Eighty-nine percent of patients tested with an open-set sentence test demonstrated enhancement of speech understanding as a result of lip-reading improvement when auditory brainstem implant sound was combined with lip-reading. A few patients (36%) had some speech understanding in sound-only mode. One patient was able to have limited phone conversations. CONCLUSION: These results indicate that significant auditory benefit can be derived from the MXM auditory brainstem implant. PMID- 11773849 TI - The bone-anchored hearing aid in patients with a unilateral air-bone gap. AB - OBJECTIVES: To study the benefit of the application of a bone-anchored hearing aid in patients with a unilateral air-bone gap. STUDY DESIGN: Prospective evaluation in eight patients. METHODS: Binaural hearing was assessed in the sound field by comparing aided and unaided scores obtained with a sound localization test and a speech recognition in noise test with spatially separated sound and noise sources. SETTING: Tertiary referral center. PATIENTS: The patients had subnormal hearing and unilateral conductive hearing loss. RESULTS: Sound localization improved significantly in the six patients with acquired hearing loss. The binaural advantage, studied with speech-in-noise tests with spatially separated speech and noise sources, proved to be comparable with that in a control group of subjects with normal hearing when they were listening monaurally versus binaurally. For one of the two patients with unilateral congenital conductive hearing loss, the results were ambiguous. This patient's age at the time of surgery was high: 40 years (the other patient was 19 years old at the time of surgery). This might have played a role. CONCLUSION: If reconstructive surgery is not possible (e.g., in a patient with a chronically draining ear or a severe congenital malformation), a bone-anchored hearing aid is an option to reestablish binaural hearing. The results reported herein suggest that, at least for patients with acquired hearing loss, the bone-anchored hearing aid is an effective treatment of unilateral conductive hearing loss. PMID- 11773850 TI - Vestibular nerve sectioning for intractable vertigo: efficacy of simplified retrosigmoid approach. AB - OBJECTIVE: To determine the surgical efficacy of a simplified retrosigmoid approach for vestibular nerve sectioning. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary academic referral center. PATIENTS: Twenty-eight consecutive patients who underwent vestibular nerve sectioning for intractable peripheral vestibular disorders. INTERVENTION: All patients had a simplified retrosigmoid approach for vestibular nerve sectioning. MAIN OUTCOME MEASURES: Functional outcome after vestibular nerve sectioning was analyzed with respect to improvement in patient disability from vertigo and reduction in the frequency of definitive vertigo attacks. Resolution of lightheadedness provided an additional outcome measure. The incidence of surgical complications, including postoperative headache, was determined, and the operative time was reviewed. RESULTS: Twenty six patients (92.9%) had an improved functional level postoperatively, 21 (75.0%) had excellent improvement, 4 (14.3%) had significant improvement, 1 (3.6%) had limited improvement, and 2 (7.1%) had no change. No patient was worse postoperatively. Eighteen of 23 Meniere's patients (78.3%) had complete control of definitive vertigo attacks after vestibular nerve sectioning. Improvement in lightheadedness was seen in 23 patients (82.1%), 11 (39.3%) of whom reported complete resolution. Postoperative headache developed in 1 (3.6%) patient. No patients experienced infection, facial weakness, or leakage of cerebrospinal fluid. Mild hearing deterioration was seen in 2 patients (7.1%). The mean operative time was 76.3 minutes. CONCLUSION: With excellent efficacy, short operative time, and a low incidence of postoperative hearing loss or headache, this simplified retrosigmoid technique should be considered for vestibular nerve sectioning in patients with intractable peripheral vestibular disorders. PMID- 11773851 TI - Meniere's disease in the elderly. AB - OBJECTIVES: To assess the prevalence, presentation, treatment, and evolution of Meniere's disease in elderly patients (> or = 65 yr old). STUDY DESIGN: Retrospective clinical study and case report. SETTING: A neuro-otology referral center at the university hospital in Bern, Switzerland, and a neurotologic practice in Geneva, Switzerland. PATIENTS: Patients were selected from the hospital clinic and otolaryngologic practice registers. Among 8423 neurotologic checkups performed between 1988 and 1998, 432 (5.1%) patients had definite Meniere's disease and 66 (15.3%) of these patients were > or = 65 years old. INTERVENTION: The files of these 66 patients were analyzed. RESULTS: Meniere's disease in the elderly had 2 modes of presentation: reactivation of longstanding Meniere's disease (40.9%) and de novo Meniere's disease (59.1%), where the first dizzy spells, tinnitus, and hearing loss appeared after 65 years of age. Drop attacks occurred in 11.1 and 25.6% of the cases, respectively, and could be responsible for misdiagnosis of strokes of the brainstem. The patients were treated by mild antivertiginous drugs (betahistine, cinnarizine). Twenty-seven patients (41%) underwent surgery: transtympanic ventilation tubes (19 patients), sacculotomy (4 patients), vestibular neurectomy (3 patients), surgical labyrinthectomy (1 patient). The vertigo spells disappeared in 73.3 to 100% of the cases according to the type of surgery performed. CONCLUSION: Our study shows that Meniere's disease in the elderly is not at all uncommon. It can appear as a de novo disease or as a reactivated longstanding disease. Drop attacks are more frequent than reported in general patient populations with Meniere's disease and can mimic a stroke of the brainstem. Medical and surgical treatments have to be cautious because many of these elderly patients are fragile. PMID- 11773852 TI - Effectiveness of the particle repositioning maneuver in benign paroxysmal positional vertigo with and without additional vestibular pathology. AB - OBJECTIVE: We compared the treatment outcome of patients with benign paroxysmal positional vertigo unassociated with additional objective evidence of vestibular pathology (BPPV) with that in patients who did demonstrate additional vestibular pathology on standard neurotologic testing (BPPV+). STUDY DESIGN: An open, retrospective, record-based study. SETTING: Specialized outpatient dizziness clinic. PATIENTS AND METHODS: We reviewed 58 unselected patients with a Dix Hallpike test demonstrating positioning nystagmus characteristic of BPPV, who were treated during the past 4 years with the particle repositioning maneuver. Before treatment, all patients underwent detailed clinical and laboratory neurotological testing. MAIN OUTCOME MEASURES: The treatment outcome was assessed with regard to persistence of symptoms and the presence of positioning nystagmus on Dix-Hallpike testing. RESULTS: Seventy-eight percent of patients with BPPV no longer demonstrated characteristic positional nystagmus after 1 particle repositioning maneuver compared with 71% of patients with BPPV+ (p = 0.56) who did, whereas 13% of the BPPV and 14% of the BPPV+ group required more than 1 treatment to be rendered nystagmus negative on Dix-Hallpike testing (p = 0.89). However, 14% of patients with BPPV remained dizzy, compared with 63% patients from the BPPV+ group, despite a negative Dix-Hallpike test after treatment (p = 0.0018). Patients with horizontal canal paresis (n = 15) had a better outcome than patients with central vestibular dysfunction (n = 7, p = 0.006). Etiologic factors seemed to affect outcome-patients with idiopathic BPPV and those with a preceding acute vestibular neuronitis had a tendency for a better outcome than BPPV patients with any other etiology (p = 0.058). CONCLUSION: Our study demonstrates that patients with BPPV+ do not have a worse prognosis with respect to resolution of positional nystagmus, on performing the particle repositioning procedure, compared with patients with uncomplicated BPPV. However, they do suffer incomplete resolution of symptoms because of a coincidental anterior or horizontal canal dysfunction and otolithic or central vestibular dysfunction. It appears that the majority of patients with BPPV+ need further vestibular rehabilitation after the particle repositioning maneuver. PMID- 11773853 TI - Radiologic differentiation of intracranial epidermoids from arachnoid cysts. AB - OBJECTIVE: Intracranial epidermoids (cholesteatomas) mimic arachnoid cysts in their radiologic characteristics, especially in the cerebellopontine angle. It is essential to differentiate the two conditions because they warrant different therapeutic interventions. The objective of this study is to elucidate the different radiologic characteristics of the conditions. STUDY DESIGN AND SETTING: This was a retrospective study of 4 patients referred for a differential diagnosis and management of intracranial cystic lesions to the Departments of Neurotology/Neurosurgery and Neuroradiology in a tertiary referral university hospital. PATIENTS: Four patients of different age groups with cystic intracranial lesions, diagnosed epidermoid or arachnoid cysts, were chosen. A retrospective analysis of their case charts, radiologic and surgical interventions, and follow-up records was undertaken. METHODS: The imaging techniques used included computerized tomographic scans, magnetic resonance imaging (MRI) with T1, T2, proton-density, and gadolinium-enhanced T1 images. In addition, special MRI sequences were used that included fluid-attenuated inversion recovery and echo planar diffusion scanning. All the patients underwent an audiovestibular evaluation. RESULTS: Both lesions are characteristically well demarcated and have a homogeneous low density, similar to cerebrospinal fluid on computerized tomographic scan, showing no contrast enhancement. On MRI, epidermoids and arachnoid cysts usually appear hypointense on T1-weighted images and hyperintense on T2-weighted images. On fluid-attenuated inversion recovery, an arachnoid cyst tends to follow cerebrospinal fluid intensity, whereas an epidermoid becomes hyperintense. There are occasions when an epidermoid may appear as a low-intensity lesion on fluid-attenuated inversion recovery. This dilemma is resolved with the use of echo planar diffusion scanning, on which an epidermoid remains bright. CONCLUSION: The authors recommend the use of fluid attenuated inversion recovery and diffusion sequence MRI when definitive radiologic diagnosis of cystic intracranial lesions becomes difficult with routine computerized tomographic scanning and MRI. PMID- 11773854 TI - Prediction of facial nerve outcome using electromyographic responses in acoustic neuroma surgery. AB - OBJECTIVE: To determine whether early and late postoperative facial nerve function can be predicted on the basis of electromyographic responses in acoustic neuroma surgery. SETTING: Prospective blinded study. DESIGN: Tertiary referral center. PATIENTS AND METHODS: Burst and train electromyographic responses were recorded intraoperatively during the last step of vestibular schwannoma removal. The responses were classified and compared with early and late postoperative facial function in 49 patients who underwent enlarged translabyrinthine acoustic neuroma surgery. RESULTS: In the early postoperative period, 20 of 22 patients with an irritable pattern and 10 of 13 patients with an ordinary pattern had Grade III or better facial nerve function, whereas all 3 patients with a stray pattern and 9 of 11 patients with a silent pattern had Grade V or VI. In the late postoperative period, on the other hand, Grade III or better facial nerve function was achieved in 37 of 38 patients with an irritable, stray, or ordinary pattern, but the facial nerve function remained at Grade V or VI in 2 patients with the silent pattern. CONCLUSION: Patients with mechanically evoked facial electromyographic responses to the last step of tumor dissection may not experience severe facial nerve dysfunction or show a remarkable improvement. However, patients with silent electromyographic responses during this step tend to experience severe facial nerve dysfunction early in the postoperative course, and some patients may not show any functional improvement. PMID- 11773856 TI - Stapediovestibular dislocation. PMID- 11773855 TI - Hearing loss and the invention of the phonograph: the story of Thomas Alva Edison. PMID- 11773857 TI - Histopathology of paragangliomas. PMID- 11773858 TI - A polymorphism (A118G) in the mu-opioid receptor gene affects the response to morphine-6-glucuronide in humans. PMID- 11773859 TI - The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. AB - Large individual differences in the clinical response to morphine therapy have been known for a long time by clinicians. The recent advances in genomic research encourage the search for pharmacogenetic causes of that variability. As a measure of central opioid effects, pupil diameters were assessed every 20 min for 18 h after administration of morphine or its active metabolite morphine-6-glucuronide (M6G) in a two-way crossover study. The opioid effects were compared between six subjects with a single-nucleotide polymorphism (SNP) A118G in the mu-opioid receptor gene (five heterozygous, one homozygous) and six control subjects. Non parametric pharmacokinetic-pharmacodynamic modelling was employed to identify the influence of the A118G SNP on the concentration-response relationship of M6G and morphine, which was described by a sigmoid Emax model. As a measure of potency, the EC50 of the pupil constrictory effects of M6G was 714 +/- 197 nmol/l in wild type and 1475 +/- 424 nmol/l in heterozygous carriers of the A118G SNP. In the homozygous carrier of the SNP, it had an EC50 of 3140 nmol/l. In addition, the dose-response relationship was flatter in the A118G carriers than in control subjects (shape factor of the sigmoid Emax model: gamma = 3.3 +/- 1.2, 1.7 +/- 0.5 and 1.6 for wild-type, heterozygous and the homozygous A118G carriers, respectively). In contrast, the concentration-response relationship of morphine was not affected by this specific SNP. The A118G SNP in the mu-receptor gene significantly reduces the potency of M6G in humans. PMID- 11773860 TI - Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) pharmacogenetics: gene resequencing, genetic polymorphisms and functional characterization of variant allozymes. AB - 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes. SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5'-triphosphate (ATP) and inorganic sulfate (SO2-4) by two isoforms, PAPSS1 and PAPSS2. Rare mutations that inactivate PAPSS2 are associated with human spondyloepimetaphyseal dysplasia and murine brachymorphism. To determine whether more common genetic polymorphisms that do not completely inactivate the enzyme might be one factor responsible for individual differences in sulfate conjugation, we previously cloned the human PAPSS2 gene. In the present studies, we 'resequenced' all twelve PAPSS2 exons and splice junctions, as well as approximately 500 bp of the 5'-flanking region, using 90 Polymorphism Discovery Resource (PDR) DNA samples from the Coriell Cell Repository. Twenty-two single nucleotide polymorphisms (SNPs) were observed, including four nonsynonymous coding region SNPs (cSNPs) that altered the following amino acids: Glu10Lys, Met281Leu,Val291Met and Arg432Lys. We also observed four insertions/deletions, including one sample that was homozygous for an 81-bp deletion in the 5'-flanking region 286 bp upstream from the site of transcription initiation. Transient expression studies showed that two of the nonsynonymous cSNPS, those that resulted in Glu10Lys and Val291Met alterations in encoded amino acids, showed significant decreases in levels of PAPSS activity. In the case of Glu10Lys, decreased activity was paralleled by a decrease in immunoreactive protein, while the Val291Met allozyme displayed a significant decrease in affinity for both ATP and Na2SO4 when compared to 'wild-type' enzyme, but without a significant alteration in level of immunoreactive protein. It will now be possible to test the hypothesis that these common, functionally significant PAPSS2 genetic polymorphisms might contribute to variations in sulfate conjugation in vivo. PMID- 11773861 TI - Genetic, pharmacological and functional analysis of cholecystokinin-1 and cholecystokinin-2 receptor polymorphism in type 2 diabetes and obese patients. AB - Cholecystokinin (CCK) and gastrin (G) and their receptors (CCK1 and CCK2) are involved in multiple physiological functions. Notably, CCK1R plays a role in the regulation of food intake whereas both CCK1R and CCK2R play a role in the regulation of pancreatic endocrine function. CCK1R and CCK2R may therefore serve as pharmacological targets in diabetes and obesity and genes encoding these receptors may be candidate genes in the pathogenesis of the diseases. In this study, we used single nucleotide polymorphism analysis and allele specific amplification for mutation screening of the CCK2 receptor gene and family linkage study. Mutated receptors were constructed, expressed in COS-7 cells for analysis of their binding and functional properties. V125I-CCK2 receptor variant was found in 2 out of 18 type 2 diabetes mellitus families tested. V125I mutation co segregated in those 2 initial families, but further association studies showed that this mutation was not associated with diabetes or early age at diagnosis of the disease. V125I-CCK2 receptor high affinity sites exhibited a 2-fold enhanced binding affinity for CCK which was correlated to a slightly increased potency in coupling to inositol phosphate production. Since CCK2 receptor is expressed in pancreatic glucagon-producing cells in humans and is involved in secretion of glucagon, an increase of binding affinity of the mutated CCK2 receptor could enhance glucagon secretion in patients bearing V125I mutation. We also characterized a mutant of the CCK1 receptor which was previously identified in an obese patient. This mutant, V365I-CCK1, demonstrated a decreased level of expression (26%) and efficacy (25%) to stimulate inositol phosphates. It can therefore be expected that in humans bearing V365I mutation, decreases in CCK1 receptor expression and coupling efficiency may affect CCK-induced regulation of satiety. Polymorphism or mutations in the CCK receptors may be involved in type 2 diabetes mellitus and obesity. However, further studies are necessary to precisely evaluate this role in humans. PMID- 11773862 TI - Clinical significance of a NAD(P)H: quinone oxidoreductase 1 polymorphism in patients with disseminated peritoneal cancer receiving intraperitoneal hyperthermic chemotherapy with mitomycin C. AB - Recent data indicate that NAD(P)H: quinone oxidoreductase 1 (NQO1) is important in the activation of mitomycin C. A polymorphism in human NQO1 (609C>T) is associated with diminished NQO1 activity. The purpose of our study was to determine the effect of the 609C>T polymorphism on tumor NQO1 activity and overall survival in patients with disseminated peritoneal cancer receiving intraperitoneal mitomycin C therapy. Patients with disseminated peritoneal cancer of gastrointestinal or other origin were eligible. Following aggressive surgical debulking, patients were administered a 2-h heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. NQO1 activity was determined in tumor tissue obtained during surgery and patients were genotyped for the NQO1 C609T polymorphism using a polymerase chain reaction-based method. The major response variable monitored during the trial was overall survival. Of the 117 patients genotyped for the NQO1 609C>T polymorphism, 67% were wild-type (WT), 31% were heterozygous (HE), and 2% were homozygous mutant (HM). In tumor tissue, the mean NQO1 activities from WT (n = 14) and HE (n = 5) patients were 794 +/- 603 and 70 +/- 133.1 nmol/min/mg protein respectively (P = 0.006). Significant differences in survival between WT versus HE/HM genotypes were noted in optimally debulked patients (R0/R1) (43.6+ months, median not yet reached versus 23 months respectively, P = 0.037) and in patients with peritoneal carcinomatosis of colonic origin (18.2 versus 11.5 months respectively, P = 0.050). These data indicate that the NQO1 609C>T polymorphism results in significantly reduced tumor NQO1 activity and reduced survival in subsets of patients receiving intraperitoneal hyperthermic mitomycin C therapy. PMID- 11773863 TI - Analysis of six SNPs of NAT2 in Ngawbe and Embera Amerindians of Panama and determination of the Embera acetylation phenotype using caffeine. AB - Six NAT2 single-nucleotide polymorphisms (SNPs) were analysed in 105 unrelated Ngawbe and 136 unrelated Embera Amerindians (482 chromosomes) by SNP-specific polymerase chain reaction analysis. 282C>T was the most common synonymous mutation, while 857G>A was the most frequent nonsynonymous inactivating exchange. The allelic frequency of the NAT2*5 series (containing the 341T>C exchange) was 2.4% and 9.9% for Ngawbe and Embera, respectively, five- to 20-times lower than that in Caucasians. The NAT2*6 series (590G>A) showed allelic frequencies of 0% and 3.7%, eight- to 30-times lower than in Caucasians. On the other hand, the NAT2*7 series, characterized by mutation 857G>A, had allelic frequencies (23.3% and 22.8%) that were 10-20-times higher in Amerindians than in Caucasians. Amerindians are characterized by decreased genetic diversity because they display a low number of mutated alleles (four and five for Ngawbe and Embera, respectively) that are present at low proportions (27.6% and 39%), reduced genotypic variability (seven out of 15 and 12 out of 21 possible genotypes) and low heterozygosity (40% and 55.1%) at the NAT2 locus. The NAT2 phenotype was evaluated with caffeine in a subset of 72 Embera. There were no disagreements between genotype and phenotype among rapid and slow acetylators (13/72, 18%). We conclude that, in the Embera, the analysis of three inactivating mutations was sufficient in predicting the phenotype in more than 99.5% of these subjects. NAT2 would appear to be of a selectively neutral character given that there is no evidence of adaptation to the prevailing ecology in Amerindians. PMID- 11773864 TI - Arylamine N-acetyltransferase type 2 and glutathione S-transferases M1 and T1 polymorphisms in familial adenomatous polyposis. AB - Familial adenomatous polyposis (FAP) exhibits a variable phenotype even in carriers of the same adenomatous polyposis coli germline mutation. Xenobiotic metabolizing enzymes such as N-acetyltransferases (NATs) and glutathione S transferases (GSTs) were reported to modify the individual risk for colorectal cancer. We examined whether the polymorphisms of the NAT2, GSTM1, and GSTT1 enzymes affect age at diagnosis of first colorectal adenomas or extracolonic manifestations in 411 FAP patients. Neither age at diagnosis of colorectal adenomas nor occurrence of extra-intestinal tumors differed significantly between genotypes at the NAT2 and GSTM1 loci, whereas GSTT1 polymorphism showed an uncertain association with extra-intestinal manifestations. Combinations of supposed at risk genotypes of the three enzymes showed no significant differences either. Thus, NAT2, GSTM1, or GSTT1 are unlikely to modify the disease phenotype in FAP patients. PMID- 11773865 TI - Implications of circadian gene expression in kidney, liver and the effects of fasting on pharmacogenomic studies. AB - Pharmacogenomics offers the potential to define metabolic pathways and to provide increased knowledge of drug actions. We studied relative levels of gene expression in the rat using a microarray with 8448 rat UniGenes (1928 known genes, 6520 unknown ESTs) in the liver and kidney as a function of time of day and then of feeding regime, which are common variables in preclinical pharmacogenomic studies. We identified 597 genes, including several key metabolic pathways, whose relative expression levels are significantly affected by time of day: expression of some was further modified by feeding state. These would have sparked interest in a pharmacogenomic study. Our study demonstrates that two common variables in pharmacogenomic studies can have dramatic effects on gene expression. This study provides investigators with baseline information for both kidney and liver with respect to 'normal' changes in gene expression influenced by time of day and feeding state. It also identifies 18 new genes that should be investigated for a role in circadian rhythms in peripheral tissues. PMID- 11773866 TI - Combined COMT and GST genotypes and hormone replacement therapy associated breast cancer risk. AB - Our previous studies suggested that both COMT and GST genotypes might modify individual breast cancer risk. Here, we extended the studies to examine the potential combined effect of these genotypes in susceptibility to breast cancer. Our study population consisted of 483 Finnish breast cancer cases and 482 population control subjects. The odds ratios (ORs) and (95%) confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected confounding factors. No significant increase in the overall breast cancer risk was seen for any combinations of the studied genotypes. However, a substantially increased risk of breast cancer was seen for women who had used hormone replacement therapy (HRT) and simultaneously carried the COMT-L allele containing genotypes and either the GSTP1 Ile/Ile genotype (OR 4.10, 95% CI 1.24 13.6) or the GSTT1 null genotype (OR 4.19, 95% CI 1.30-13.5). These associations appeared to be mainly attributable to long-term users of HRT; the respective ORs were 7.00 (95% CI 1.21-40.6) and 8.36 (95% CI 1.44-49.0) among the users of HRT of more than 30 months. In addition, the combination of COMT-L allele containing genotypes with the GSTM1 null genotype posed a remarkably increased risk (OR 9.10, 95% CI 1.84-45.0) of breast cancer in this study group. These results suggest that the use of HRT could substantially increase the risk of breast cancer among women with specific combinations of the at-risk genotypes of COMT and GST genes. PMID- 11773867 TI - Visual disorders associated with omeprazole and their relation to CYP2C19 polymorphism. AB - Risk factors for patients developing visual disturbances in association with proton pump inhibitors are unknown. As omeprazole is substantially metabolized by polymorphic CYP2C19, we retrospectively identified and genotyped patients who experienced this adverse reaction. Among 29 patients, we found two poor metabolizers (PMs) of CYP2C19. The PM genotype does not appear to be a risk factor for omeprazole-associated visual disorders. PMID- 11773868 TI - Ethnic differences in allelic frequency of two flavin-containing monooxygenase 3 (FMO3) polymorphisms: linkage and effects on in vivo and in vitro FMO activities. PMID- 11773869 TI - Genetic polymorphisms of UDP-glucuronosyltransferase in Asians: UGT1A1*28 is a common allele in Indians. PMID- 11773870 TI - Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2 genotype. PMID- 11773871 TI - Hospitalization rates in female US Army recruits associated with a screening program for Chlamydia trachomatis. AB - BACKGROUND: A volunteer program to test non-healthcare-seeking women for genital Chlamydia trachomatis infection was instituted at the US Army's largest basic training center and evaluated for its effectiveness in reducing sequelae. GOAL: To compare hospitalization rates between women with positive test results for C trachomatis and those with negative results, and between women tested and those not tested for C trachomatis. STUDY DESIGN: For this study, 28,074 women who entered the Army in 1996 and 1997 were followed for hospitalizations through December 1998. Of these women, 7053 were tested for C trachomatis, and 21,021 were not screened. Hospital admissions were calculated per person-year, and adjusted relative risks were determined. RESULTS: The overall prevalence of C trachomatis in the screened group was 9.1%. The relative risk of hospitalization for pelvic inflammatory disease in the screened cohort was 0.94 (95% CI, 0.69 1.29), as compared with those not screened. The relative risk of hospitalization for any reason was 0.94 (95% CI, 0.90-0.99). Among women screened, no difference was found in pelvic inflammatory disease hospitalizations between women with positive test results who were being treated for C trachomatis and those with negative test results. CONCLUSIONS: The investigated C trachomatis intervention program for female Army recruits was associated with a lower overall hospitalization rate in screened volunteers, as compared with unscreened women. The pelvic inflammatory disease hospitalization rate in women with C trachomatis who were screened and treated was similar to that observed in uninfected women. PMID- 11773872 TI - Anticipating outbreaks: a prevention role for integrated information systems. PMID- 11773873 TI - American adolescents: sexual mixing patterns, bridge partners, and concurrency. AB - BACKGROUND: American adolescents have a high incidence of sexually transmitted infections. Patterns of sexual partner choice influence the transmission of infections in this population. GOAL: To examine patterns of sexual mixing, bridging, and concurrency in American adolescents and the association of these characteristics with condom use. STUDY DESIGN: This project used the AddHEALTH survey data. The survey selected a sample of schools, then conducted in-home interviews with 18,984 students in 1995. A second wave of data collection was conducted 2 years later. The data on sexual relationships collected in the study were analyzed. RESULTS: Respondents ranged in age from 13 to 17 years. Sex partnerships with persons of differing age groups were very common in this population (45% of sexual partnerships). Relationships with persons of different ethnicity were more common among Latinos (42%) than among white (14%) and black (15%) respondents. A large proportion of the sample reported more than two partners (56%). Among these persons, a large proportion reported partners in two different age groups (69%) and ethnic groups (35%) as well as concurrent partners (54%). Condom use was lower among persons with partners in different age groups and among persons with a larger number of partners. CONCLUSIONS: The large number of adolescents who have sexual relationships with persons of different characteristics creates bridges for infections between different groups. Counseling of sexually active adolescents should include discussion on issues of power and communication in these relationships. PMID- 11773874 TI - Sexual risk behaviors associated with having older sex partners: a study of black adolescent females. AB - BACKGROUND: Volunteer black adolescent females from neighborhoods characterized by high rates of unemployment, substance abuse, violence, and sexually transmitted disease were studied to determine the frequency of condom use and unprotected vaginal sex with steady, older partners during various time periods over the previous 6 months. GOAL: To examine associations between having male sex partners who were typically older (by at least 2 years) and adolescent females' sexually transmitted disease (STD)/HIV-associated sexual risk behaviors. STUDY DESIGN: In this cross-sectional study, 522 sexually active black adolescent females completed a questionnaire and a structured interview, of which a portion assessed the age difference between the adolescents and their typical sex partners. The adolescents' ages, length of relationship and their use of hormonal contraception were identified as covariates. Adjusted odds ratios (AOR), their 95% confidence intervals, and respective P values were calculated to detect significant associations. RESULTS: Sixty-two percent of the adolescents reported their typical sex partners were at least 2 years older. These adolescents were more likely to report never using condoms during the most recent sexual encounter (AOR = 2.0), during the last five sexual encounters (AOR = 2.0), and during the past month (AOR = 2.2). Similarly, having older partners was associated with greater odds of reporting any unprotected vaginal sex in the past 30 days (AOR = 1.7) or the past 6 months (AOR = 1.5). CONCLUSION: Our findings suggest that many adolescent females have sex partners who are at least 2 years older and that their relationship dynamics do not favor the adoption and maintenance of behavior protective against STD or HIV infection. Prevention programs could include training designed to help adolescent females overcome barriers to safer sex with older male partners. PMID- 11773875 TI - Pulsed-field gel electrophoresis as an epidemiologic tool for Neisseria gonorrhoeae: identification of clusters within serovars. AB - BACKGROUND: The increasing incidence of gonorrhea in Sweden in 1998 was due to mostly domestic cases. Among these, two core groups were identified: homosexual men with serovar IB-2 and young heterosexuals with serovar IB-3. GOALS: To explore the genetic homogeneity/heterogeneity within the predominant serovars, IB 2 and IB-3, of Neisseria gonorrhoeae in Sweden by pulsed-field gel electrophoresis (PFGE) and to compare these results to epidemiologic information, as well as examine the genetic diversity within and between the 25 other represented serovars of N gonorrhoeae. STUDY DESIGN: By PFGE, 237 N gonorrhoeae isolates were examined, and the results were compared with epidemiologic data for the IB-2 and IB-3 isolates. RESULTS: In 79% of the domestic IB-2 cases involving homosexuals and 66% of the domestic IB-3 cases involving young heterosexuals, the isolates were genetically indistinguishable by PFGE. A high genetic diversity was identified within and between the 27 included serovars. CONCLUSIONS: Examination by means of PFGE indicated that one N gonorrhoeae clone each of the serovars IB-2 and IB-3 created the majority of the two core groups of domestic cases. PMID- 11773876 TI - A case study of antenatal syphilis screening in South Africa: successes and challenges. AB - BACKGROUND: To evaluate the process of providing routine syphilis screening to antenatal care (ANC) clients at primary healthcare clinics in KwaZulu-Natal Province, South Africa. GOAL: To document the program performance and make recommendations for improving the current program and informing proposals for on site testing. STUDY DESIGN: Nine health facilities were recruited for the study. The methodology used for this case study included: Key informant interviews, inventory, focus group discussions with clients, client flow analysis, exit interviews with clients and observations of consultations. RESULTS: All 51 women attending their first ANC visit had a blood sample taken for a syphilis rapid plasma reagin (RPR) test. Unreliable transport resulted in an average 4 weeks turnaround time to get RPR test results back to clinics. Due to late presentation in the pregnancy for their first ANC visit, 15% would have been unable to complete their treatment before delivery if they had been found positive. Health providers gave minimal information and/or counseling on syphilis, neither did they stress the importance of treatment of positive clients and their partners. There was no strategy to track positive clients who had not been treated or their partners. Providers were unclear on whether partners should be tested before treatment. CONCLUSION: Although testing was readily available, most of the constraints were centered round logistics of ensuring treatment of women and their partners. These issues must be addressed by sexually transmitted infection managers and policymakers. PMID- 11773877 TI - Reducing the risk of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use. AB - BACKGROUND: Sexual acquisition of HIV is influenced by choice of partner, sex act, and condom use. However, current risk-reduction strategies focus mainly on condom use. GOAL: To estimate the contribution of choice of partner, sex act, and condom use on the per-act relative and absolute risks for HIV infection. STUDY DESIGN: Per-act relative risk for HIV infection was calculated with use of estimates of HIV prevalence, risk of condom failure, HIV test accuracy, and per act risk of HIV transmission for different sex acts. Absolute risks were calculated on the basis of these relative risk estimates. RESULTS: Choosing a partner who tested negative instead of an untested partner reduced the relative risk of HIV infection 47-fold; using condoms, 20-fold; and choosing insertive fellatio rather than insertive anal sex, 13-fold. Choosing one risk-reduction behavior substantially reduces absolute risk of HIV infection for heterosexuals but not for men who have sex with men. CONCLUSION: Clarifying the magnitude of risk associated with different choices may help people make effective and sustainable changes in behavior. PMID- 11773878 TI - Prevalence of HIV among truck drivers visiting sex workers in KwaZulu-Natal, South Africa. AB - BACKGROUND: Although the role of mobile populations in the spread of HIV has been documented in several countries, there are few data on HIV among truck drivers in South Africa and the sex workers with whom they interact. GOAL: To determine HIV prevalence and risk behavior in a sample of truck drivers visiting commercial sex workers at truck stops. STUDY DESIGN: Two sex workers from each of five truck stops were trained to obtain informed consent, administer questionnaires to obtain data on demographic and migration patterns, and collect saliva samples for HIV testing from their clients. Data on HIV prevalence and demographic characteristics of sex workers operating at the truck stops were obtained from an ongoing vaginal microbicide trial. RESULTS: The mean age of the truck drivers (all men) was 37 years (range, 18-71 years), and that of the sex workers (all females) was 25 years (range, 15-49 years). Sixty-six percent of the men reported having a sexually transmitted infection in the previous six months, and 37% always stopped for sex along the route. Twenty-nine percent reported never using condoms with sex workers, whereas 13% had used condoms with their wives. All men traveled to more than one province in South Africa, and 65% traveled to neighboring countries. Anal sex was practiced by 42% of the men. The overall HIV prevalence (in the two groups combined) was 56%. CONCLUSION: Truck drivers may have facilitated the spread of HIV infection throughout southern Africa. PMID- 11773879 TI - The Bali STD/AIDS Study: evaluation of an intervention for sex workers. AB - BACKGROUND: Prostitution has been an important factor in the spread of HIV infection in Asia. Interventions need to be developed to reduce the risk of transmission of sexually transmitted infections in this area. GOALS: To educate female sex workers about sexually transmitted infections and assess the impact of the educational intervention. STUDY DESIGN: Brothel areas in Denpasar, Bali, Indonesia, were divided into areas of high and low program (interventional) effort. The intervention included educational sessions for sex workers, treatment of sex workers for sexually transmitted disease (STD), condom distribution, and printed information for clients of the sex workers. A high-effort area was one in which a more intensive educational intervention occurred. A clinic was available for STD treatment in both areas. Behavioral surveys and STD testing were used to evaluate the programs. Six hundred female sex workers participated in behavioral surveys and STD examinations every 6 months for four rounds of data collection. Each round, about half of the women were new to the study. A total of 1586 women participated in at least one evaluation round. Changes were evaluated in AIDS knowledge, STD knowledge, and condom use, as well as in the prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and Trichomonas vaginalis. Testing for HIV was conducted anonymously. RESULTS: Improvements were noted in the knowledge of sex workers about AIDS and STDs and in the reduction of some bacterial STDs. Women who remained in the study area for more than one round had increased knowledge of HIV infection/STDs and condom use and had reduced levels of syphilis, gonorrhea, and trichomonas infection (P < 0.01). The additional education received by women in the high-effort program area was associated with a reduction in the prevalence of syphilis. Prevalence of HIV remained low throughout the study. The high level of turnover of female sex workers contributed to the maintenance of significant levels of STDs in this population. CONCLUSIONS: Developers of HIV/STD prevention programs for sex workers need to consider the mobility of the sex worker population. Interventions combining behavioral and medical approaches can contribute to prevention of these diseases. PMID- 11773880 TI - Interrelationships of bacterial vaginosis and cervical inflammation. AB - BACKGROUND: Women with cervicitis frequently have bacterial vaginosis (BV). Prior studies have suggested that BV is involved in the pathogenesis of cervicitis. GOALS: To delineate the association of BV and cervicitis and to determine whether treatment of BV results in increased resolution of cervicitis. STUDY DESIGN: Women with clinically diagnosed cervicitis and BV received doxycycline and ofloxacin and were randomized to treatment with metronidazole gel or placebo. Resolution of BV and cervicitis was assessed. RESULTS: Metronidazole gel was associated with resolution of BV. Resolution of cervicitis was associated with use of metronidazole gel versus placebo (24/27 [88.9%] versus 15/24 [62.5%]; P = 0.03). When further stratified by resolution of BV, those whose BV resolved were more likely to have resolution of cervicitis than those with persistent BV. Although these trends persisted in multivariate analyses, they did not achieve statistical significance. CONCLUSION: Univariate analyses suggest an association between BV and cervicitis. An association between the use of metronidazole gel and resolution of cervicitis was demonstrated. Hypotheses regarding the latter include nonspecific antiinflammatory effects of metronidazole, its effect on BV flora, and its effect on a specific unrecognized pathogen. PMID- 11773881 TI - Will some pig breeds or tissues be less likely to express infectious PERV? PMID- 11773882 TI - Transplantation of mouse pancreatic islets into primates--in vivo and in vitro evaluation. AB - BACKGROUND: Islets transplanted from other species to man has the potential to cure diabetes but whether islets are subject to hyperacute rejection after xenotransplantation is contentious. We transplanted mouse pancreatic islets of mouse beneath the primate renal capsule and assessed natural xenoantibody binding, complement activation and cell lysis in vitro. METHODS: Freshly isolated mouse islets were transplanted in a blood clot under the renal capsule of cynolmogus monkeys. The graft was removed after 24 hr for histological and ultrastructural analysis. Freshly isolated mouse pancreatic islets were analyzed in vitro by immunohistochemistry for Gal(alpha1,3)Gal and Von Willebrand factor expression and for IgG, IgM, C3, C4, and C5b-9 binding after incubation in 100% human serum. Complement mediated cell lysis was evaluated by 51Cr release assays after incubation of islets for 4 hr in human serum, plasma, and lymph with and without added neutrophils. RESULTS: Mouse islets transplanted under the renal capsule of cynomolgus monkeys were destroyed within 24 hr by a process involving necrosis with neutrophil and mononuclear cell infiltration. Gal(alpha1,3)Gal was strongly positive on only 10% of islet cells. After islet incubation in 100% human serum before frozen section, human IgG and IgM, C3, C4, and C5b-9 was deposited on islets with increased intensity in the periphery. Measurement of 51Cr release from labeled fresh islets after four hours incubation in 100% human serum showed 17% lysis and was not changed by addition of neutrophils. CONCLUSION: These results indicate that mouse islets in a primate recipient undergo rapid destruction by a process that has features similar to hyperacute rejection in vascularized organs and we propose the same term be used. PMID- 11773883 TI - Effects of FK409 on intestinal ischemia-reperfusion injury and ischemia-induced changes in the rat mucosal villus microcirculation. AB - BACKGROUND: The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances contribute to tissue damage. Nitric oxide (NO) seems to be involved in tissue protection after I/R injury. This study therefore assessed the effects of the NO donor, FK409, on intestinal I/R injury and changes induced in intestinal microcirculation. METHODS: PVG rats were subjected to 30-min intestinal ischemia with a subgroup of animals receiving FK409 (10 mg/kg i.v.) 30 min before ischemia and 30 min postreperfusion. Controls underwent sham surgery. The mucosal surface was visualized via an incision made in an exteriorized ileal segment and FITC-BSA or acridine orange was used to quantitate macromolecular leak (MML) and leukocyte adhesion, respectively. MML from, and numbers of adherent leukocytes within, individual villi were determined every 15 min for 2 hr after removal of the vessel clamp. Heart rate and mean blood pressure (mBP) were monitored throughout the experiment. RESULTS: Eleven of 12 untreated animals subjected to intestinal I/R injury failed to survive the 2 hr reperfusion period, whereas all 12 FK409 treated animals survived. MML and leukocyte adhesion were increased in untreated animals (P<0.001), and blood flow stasis eventually ensued. Although FK409 decreased mBP (P<0.001), MML and leukocyte adhesion were significantly (P<0.001) reduced, and villus blood flow was maintained throughout the observation period. CONCLUSIONS: FK409 prevented mortality after intestinal I/R, significantly reduced leukocyte adhesion, and maintained blood flow after intestinal ischemia and may therefore be of value in reducing tissue damage and improving outcome after small bowel transplantation. PMID- 11773884 TI - Transplantation-induced endothelial dysfunction as studied in rat aorta allografts. AB - BACKGROUND: Clinical evidence indicates that vascular endothelial cell (EC) dysfunction occurs early after transplantation (Tx) and initiates chronic graft vasculopathy. This study explored this phenomenon in rat aorta Tx using the stringent Dark Agouti (DA)-to-Lewis (LEW) and the weak Fischer 344 (F344)-to-LEW strain combinations. METHODS: Donor abdominal aortae were orthotopically grafted into LEW rats. At post-Tx days 7, 14, 28, and 56, grafts were collected to assess changes in EC morphology (en face silver staining) and EC function, i.e., vasodilatory response to acetylcholine (ACH) after phenylephrine (PHE) precontraction; changes in vascular smooth muscle cell (VSMC) alpha-actin (western blotting), degree of apoptosis (caspase-3 activity), and morphology. RESULTS: In DA allografts, VSMC and EC dysfunctions developed concomitantly and were completed at 14 days post-Tx, most likely due to the EC and alpha-actin positive VSMC loss. Meanwhile, allografts revealed markedly increased caspase-3 activity. Neointima formation, restricted to the edges of allografts at day 28, covered the entire allografts by day 56 post-Tx. In F344-allografts, VSMC function was maintained up to day 14 post-Tx, whereas ACH-induced relaxation was reduced by 50% at day 7 and abolished at day 14. EC denudation was not seen up to 56 days post-Tx, despite prominent leukocyte adhesion. Neointima formation was not detected at day 28 post-Tx but appeared along the entire allografts at day 56 post-Tx. CONCLUSIONS: These results confirm that Tx-induced EC dysfunction precedes the development of vasculopathy in rat aorta allografts and suggest that this early phenomenon can be best studied in the F344-to-LEW strain combination. PMID- 11773885 TI - In vivo blockade of macrophage migration inhibitory factor prevents skin graft destruction after indirect allorecognition. AB - BACKGROUND: The effector mechanisms that ultimately destroy transplanted tissues are poorly understood. In particular, it is not clear how CD4+ T cells primed to donor-derived determinants expressed on recipient MHC molecules (the indirect pathway) can mediate graft destruction in the absence of cognate recognition of peptide: MHC on the graft cells themselves. Macrophage migration inhibitory factor (MIF) inhibits macrophage movement and is a proinflammatory and regulatory cytokine known to be essential for development of delayed-type hypersensitivity reactions. METHODS: To test whether MIF participates in graft destruction following indirect recognition, we studied rejection of MHC-II-deficient skin grafts placed on allogeneic SCID recipients adoptively transferred with naive CD4+ T cells, and the recipients were treated with neutralizing anti-MIF monoclonal antibody or isotype control IgG. In this model graft rejection can only occur indirectly as the graft cells lack MHC II for recognition by the recipient CD4+ T cells. RESULTS: We found that in vivo blockade of MIF inhibited indirect CD4+ cell-mediated skin graft destruction, and markedly reduced detectable macrophages within the grafts. The neutralizing anti-MIF antibody significantly inhibited alloreactive DTH but did not prevent T cell priming or interferon-gamma release by primed T cells. CONCLUSIONS: The results strongly implicate MIF as an active participant in skin graft destruction after indirect recognition and suggest that this effect is mediated through an inhibition of macrophage migration and/or function. PMID- 11773886 TI - Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection. AB - The critical shortage of human donor organs has generated growing interest for porcine to human xenotransplantation. The major immunological barrier to xenotransplantation is the hyperacute rejection (HAR) response that is mediated by preformed xenoreactive antibodies and complement. A promising strategy to control the complement activation, is the expression of human complement regulatory proteins in transgenic animals. We have used the human early cytomegalovirus (CMV) promoter to drive expression of the human complement regulatory protein CD59 (hCD59) in transgenic pigs. A total of eight live transgenic founder animals was born from which five transgenic lines could be established. mRNA analysis and Western blotting revealed high expression of hCD59 in heart, kidney, skeletal muscle, and skin in animals of lines 1 and 5, as well as in the pancreas of four lines. This pattern of expression was confirmed by immunhistological staining. A cell-specific expression in heart and kidney tissue of transgenic lines 1 and 5 was determined. Primary fibroblasts and endothelial cell cultures derived from the aorta of transgenic pigs showed a significantly diminished sensitivity against the challenge with xenoreactive human antibodies and complement whereas non-transgenic control cells were highly susceptible to complement mediated lysis. Ex vivo perfusion of kidneys with pooled human blood revealed a significant protective effect of hCD59 against HAR. The average survival of transgenic kidneys was significantly extended (P<0.05) over nontransgenic controls (207.5+/-54.6 vs. 57.5+/-64.5 min). These data support the concept that hCD59 protects nonprimate cells against human complement mediated lysis and suggest that donor pigs transgenic for hCD59 could play a crucial role in clinical xenotransplantation. Two of five hCD59 transgenic lines showed strong hCD59 expression in several organs relevant for xenotransplantation and a protective effect against HAR. This indicates that the use of the CMV-promoter can facilitate the selection process for optimized transgene expression. PMID- 11773887 TI - The role of alphabeta- and gammadelta-T cells in allogenic donor marrow on engraftment, chimerism, and graft-versus-host disease. AB - BACKGROUND: We previously characterized a facilitating cell (FC) in mouse marrow that enables engraftment of allogeneic hematopoietic stem cells (HSCs) without causing graft-versus-host disease (GVHD). The FC shares some cell surface molecules with T cells (Thy1+, CD3epsilon+, CD8+, CD5+, and CD2+) but is T-cell receptor (TCR) negative. Historically, depletion of CD3+ or CD8+ cells from rat marrow was associated with an increased rate of failure of engraftment. In this study, we evaluated whether depletion of alphabeta- and gammadelta-TCR(+) T cells from donor marrow would retain engraftment potential yet avoid GVHD. METHODS: Wistar-Furth rats were conditioned with 950 cGy of total body irradiation and transplanted with ACI bone marrow processed to remove either alphabeta-TCR(+), gammadelta-TCR(+), or alphabeta- plus gammadelta-TCR(+) T cells. Recipients were typed for chimerism at 28 days and monthly thereafter. RESULTS: Recipients of marrow depleted of alphabeta- (group A), gammadelta- (group B), or alphabeta- and gammadelta-TCR(+) T cells (group C) engrafted and had an average chimerism level of 73.0+/-8.3%, 92.3+/-9.2%, and 46.3+/-32.8%, respectively. Aggressive T-cell depletion did not remove the FC population (CD8+/CD3+/TCR(-)). Group A and group B both developed GVHD, with a higher incidence of GVHD in group B compared to group A. None of the recipients in group C developed GVHD. CONCLUSIONS: These data demonstrate that depletion of T cells from rat marrow does not impair engraftment of HSCs, indirectly supporting the existence of FCs in rat marrow. Moreover, donor alphabeta- and gammadelta-TCR(+) T cells contribute to GVHD in a nonredundant fashion, although alphabeta-TCR(+) T cells are more potent as the effector cells. Finally, the level of donor chimerism is influenced by the composition of the graft, because recipients of marrow that contain alphabeta TCR(+) T cells exhibited significantly higher donor chimerism compared to recipients of marrow depleted of both alphabeta- and gammadelta-TCR(+) T cells. PMID- 11773888 TI - Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection. AB - BACKGROUND: Basiliximab (Simulect), a high-affinity chimeric, monoclonal antibody directed against the alpha chain of human interleukin-2 receptor (CD25), reduces the incidence of acute renal allograft rejection when used in combination with cyclosporine (Neoral) and steroids. This study was designed to compare the safety and efficacy of basiliximab to polyclonal anti-T-cell (ATGAM) therapy for the prevention of acute rejection in de novo renal transplant recipients. METHODS: This 1-year, open-label, randomized trial was conducted in recipients of cadaveric or living-related donor renal transplants. All patients received cyclosporine (Neoral), mycophenolate mofetil (CellCept, MMF), and corticosteroids. Patients who were randomized to basiliximab therapy received a 20 mg i.v. bolus dose on days 0 and 4, and the majority of patients were initiated on cyclosporine within 48 hr of transplantation. Patients who were randomized to antithymocyte globulin therapy (ATGAM, ATG) received 15 mg/day i.v. within 48 hr of transplant and continued treatment for up to 14 days; ATG was stopped once therapeutic cyclosporine blood levels were achieved. The initiation of cyclosporine use was delayed in the ATG group until renal function was established (serum creatinine <3.0 mg/dl or 50% fall from baseline). RESULTS: Of the 138 randomized patients, 135 received at least 1 dose of study medication (70 patients, basiliximab; 65 patients, ATG). Demographic characteristics were similar between the basiliximab and ATG-treatment groups. At 12 months, the rate of biopsy-proven acute rejection was 19% and 20%, respectively, in the basiliximab and ATG groups. Although the overall profile of adverse events was similar between basiliximab- and ATG-treated patients, adverse events considered by the investigators to be associated with the study drug occurred more often among patients receiving ATG (42% vs. 11% with basiliximab). CONCLUSIONS: Basiliximab combined with early initiation of cyclosporine therapy resulted in low acute rejection rates similar to those achieved with ATG combined with delayed cyclosporine. Basiliximab therapy showed an excellent safety profile, with no increases in malignancies, infections, or deaths. Based on its convenient two-dose, body-weight independent regimen and comparable effectiveness to ATG, basiliximab is an attractive choice for the prevention of acute rejection episodes in renal transplant patients. PMID- 11773889 TI - Are wound complications after a kidney transplant more common with modern immunosuppression? AB - BACKGROUND: The most common surgical complication after a kidney transplant is likely related to the wound. The purpose of this analysis was to determine the incidence of, and risk factors for, wound complications (e.g., infections, hernias) in kidney recipients and to assess whether newer immunosuppressive drugs increase the risk for such complications. METHODS: Between January 1, 1984 and September 30, 1998, we performed 2013 adult kidney transplants. Of these 2013 recipients, 97 (4.8%) developed either a superficial or a deep wound infection. Additionally, 73 (3.6%) recipients developed either a fascial dehiscence or a hernia of the wound. We used univariate and multivariate techniques to determine significant risk factors and outcomes. RESULTS: Mean time to development of a superficial infection (defined as located above the fascia) was 11.9 days posttransplant; to development of a deep infection (defined as located below the fascia), 39.2 days; and to development of a hernia or fascial dehiscence, 12.8 months. By multivariate analysis, the most significant risk factor for a superficial or deep wound infection was obesity (defined as body mass index>30 kg/m2) (RR=4.4, P=0.0001). Other significant risk factors were a urine leak posttransplant, any reoperation through the transplant incision, diabetes, and the use of mycophenolate mofetil (MMF) (vs. azathioprine) for maintenance immunosuppression (RR=2.43, P=0.0001). Significant risk factors for a hernia or fascial dehiscence were any reoperation through the transplant incision, increased recipient age, obesity, and the use of MMF (vs. azathioprine) for maintenance immunosuppression (RR=3.54, P=0.0004). Use of antibody induction and treatment for acute rejection were not significant risk factors for either infections or hernias. Death-censored graft survival was lower in recipients who developed a wound infection (vs. those who did not); it was not lower in recipients who developed an incisional hernia or facial dehiscence (vs. those who did not). CONCLUSIONS: Despite immunosuppression including chronic steroids, the incidence of wound infections, incisional hernias, and fascial dehiscence is low in kidney recipients. As with other types of surgery, the main risk factors for postoperative complications are obesity, reoperation, and increased age. However, in kidney recipients, use of MMF (vs. azathioprine) is an additional risk factor one that potentially could be altered, especially in high-risk recipients. PMID- 11773891 TI - Horseshoe kidney transplantation within the eurotransplant region: a case control study. AB - BACKGROUND: The horseshoe kidney is the most common anatomic renal variation, with an incidence of 1 in 600 to 800. It represents a fusion anomaly, usually of the lower poles. Horseshoe kidneys can be transplanted en bloc or after division of the renal isthmus. However, the great variation in origin, number, and size of renal arteries and veins leads to some reluctance to use horseshoe kidneys for transplantation. The aim of this study is to assess the results of horseshoe kidney transplantation. METHODS: All data concerning horseshoe kidney transplantations within the Eurotransplant region were collected and were divided into en bloc and split transplantations. A matched control group was defined, and the three groups were analyzed with respect to the occurrence of primary nonfunction, graft survival, patient survival, and finally posttransplant serum creatinine values. RESULTS: From 1983 to 2000, 8 horseshoe kidneys were transplanted en bloc and 26 were split and transplanted into 47 recipients. The results of these transplantations were compared with 110 transplantations in the control group. No significant differences among the three groups could be found, either in the short- or long-term posttransplant results. CONCLUSIONS: The results of horseshoe kidney transplantation, either en bloc or split, are equal to the posttransplant results of kidneys with a normal anatomy. Bearing in mind the shortage of donors, horseshoe kidneys should certainly be used for transplantation. PMID- 11773890 TI - Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus host disease. AB - BACKGROUND: In a pilot trial we evaluated the toxicity and efficacy of sirolimus (rapamycin) as second-line therapy for the treatment of acute graft-versus-host disease (GVHD) in 21 patients (1-46 years of age) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: All patients were treated with methylprednisolone at 2 mg/kg/day, but failed to respond satisfactorily. Sirolimus was started 19-78 (median 37) days after HSCT when 10 patients had grade III and 11 had grade IV GVHD. The first four patients received a loading dose (15 mg/m2) of oral sirolimus on day 1 followed by 5 mg/m2/day for 13 days. The next 17 patients received either 5 (n=7) or 4 (n=10) mg/m2/day for 14 days without a loading dose. Eleven patients completed the 14-day sirolimus course. Five patients were treated for 9-13 days, two for 6 days, and three for 1-3 days. RESULTS: Sirolimus was discontinued early in 10 patients because of lack of improvement in GVHD (n=5), myelosuppression (n=2), seizure (n=2), and attending physician preference (n=1). The most common and significant adverse events were thrombocytopenia (n=7) and neutropenia (n=4). Other side effects included increased blood triglycerides (n=8) and cholesterol (n=3). Five patients had evidence of a hemolytic uremic syndrome concurrently with or after sirolimus treatment. Eighteen of the 21 patients received 6 or more doses of sirolimus and 12 responded, 5 with complete and 7 with partial responses. Six of the 12 responders (28% of all patients enrolled) and 1 nonresponder are currently alive at 400-907 days after HSCT, 3 with chronic GVHD. Fourteen of the 21 patients (66%) died 40-263 days after transplant. CONCLUSION: These data suggest that sirolimus has activity in the treatment of steroid-refractory acute GVHD. However, there was considerable toxicity and further dose optimization studies seem warranted. PMID- 11773892 TI - End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. AB - BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication. PMID- 11773893 TI - Risk factors and impact of cytomegalovirus disease in simultaneous pancreas kidney transplantation. AB - BACKGROUND: The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. METHODS: This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated. RESULTS: The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. CONCLUSIONS: Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed. PMID- 11773894 TI - Rare-event analysis of circulating human dendritic cell subsets and their presumptive mouse counterparts. AB - BACKGROUND: Considerable interest has focused recently on murine CD8alpha- and CD8alpha+ dendritic cell (DC) subsets, because of their roles in initiating and regulating immune responses. Attention has also centered on their presumed human counterparts, DC1 and DC2, respectively, and their precursors. Identification and quantification of these subsets in the blood may be crucial to understanding and monitoring of their immunologic significance, particularly in humans, where blood may be the only tissue readily or routinely available. METHODS: Leukocytes were isolated from anticoagulated human or mouse (C57BL/10J) blood using conventional procedures. Four-color, rare-event, flow cytometric analysis was used to identify DC1 precursors (pDC1; lineage [lin]- CD4+ CD11c+ HLA-DR+) or DC2 precursors (pDC2; lin- CD4+ CD11c- CD123(hi) [IL-3Ralpha(hi)] HLA-DR+) in normal humans. In mice, CD8alpha+ (CD11b(lo), CD11c+) and CD8alpha- (CD11b(hi), CD11c+) DC subsets were identified both in normal animals and after administration of the potent DC growth factor, fms-like tyrosine kinase 3 ligand (Flt3L). RESULTS: All human subjects examined had discrete populations of pDC1 and pDC2 comprising approximately 0.6% and 0.1% of blood mononuclear cells. CD8alpha- and CD8alpha+ DC constituted approximately 0.75% and 0.2%, respectively, of blood mononuclear cells in normal mice, and 12% and 0.5%, respectively, in Flt3L-treated animals. Flt3L administration substantially increased the absolute numbers of circulating CD11c+ DC by approximately 200-fold. CONCLUSIONS: In addition to pDC1 and CD8alpha- DC, pDC2 and CD8alpha+ DC can be identified in normal human or mouse blood, respectively. Monitoring and isolation or characterization of these cells may provide novel insights into their functional significance in transplantation and other clinical conditions. PMID- 11773895 TI - Pattern of alloimmune response in second same donor allografts after induction of tolerance using CTLA4Ig. AB - BACKGROUND: The pattern of allograft acceptance in the presence of costimulatory blockade is manifested by the sequential appearance of Th1 cells, followed by Th2 cells. The aim of this study was to examine whether this phenomenon repeats itself after second same donor allotransplantation, hoping to determine whether acceptance in this setting provokes a predominance of the Th2 response. METHODS: Tolerance was achieved by transplantation of CTLA4Ig-transduced ACI liver allografts in Lewis recipients. Recipient long-term survivors received a second transplant, consisting of a cervical heterotopic heart from the same ACI donor strain. Animals were sacrificed at predetermined intervals following the second transplant and the heart and liver were processed for histology and cytokine mRNA expression. RESULTS: Recipients of CTLA4Ig-transduced livers survived indefinitely. Rechallenge with same donor strain second allograft was manifested by an anergic immune response in the second cardiac allograft, and a very mild transient infiltrate within the first accepted liver graft. Cardiac function was maintained with resolution of all infiltrates. The cytokine cascade was activated within the allografts; however, the pattern of acceptance was not associated with predominance of a specific Th subtype. CONCLUSIONS: The pattern of acceptance of an allograft following CTLA4Ig-mediated costimulatory blockade is not related to long-term predominance of Th2 cells, a phenomenon that may be unique to the setting of a tolerant liver. It may be likely that the infiltrating lymphocytes that are dominant in the second graft are suppressed by other memory mechanisms. PMID- 11773896 TI - Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. AB - BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in human liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine receptors CXCR3, CXCR4, and CCR5 on circulating and graft-infiltrating lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. CXCR3 ligands interferon-inducible protein 10 and monokine induced by gamma interferon were detected on sinusoidal endothelium and interferon-inducible T-cell alpha chemoattractant was detected on portal and hepatic vascular endothelium, whereas the CXCR4 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. CCR5 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional CXCR3, CXCR4, and CCR5 on T cells. Increased expression of chemokine receptors, especially CCR3 and CCR5, was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors CXCR3 and CCR5 are important for recruitment, the restriction of SDF to bile ducts suggests that CXCR4 may be involved in the retention of alloactivated lymphocytes at sites of graft damage. PMID- 11773897 TI - Human serum-induced expression of E-selectin on porcine aortic endothelial cells in vitro is totally complement mediated. AB - BACKGROUND: Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation. METHODS: An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in microculture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression. RESULTS: E-selectin was strongly induced by normal human serum but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a monoclonal antibody (mAb) that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel antifactor D mAb did not reduce E-selectin expression. CONCLUSION: Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts. PMID- 11773898 TI - Donor-derived soluble MHC antigens plus low-dose cyclosporine induce transplantation unresponsiveness independent of the thymus by down-regulating T cell-mediated alloresponses in a rat transplantation model. AB - BACKGROUND: In vitro, soluble MHC (sMHC) antigens modulate and induce apoptosis in alloreactive and antigen-specific T cells, demonstrating their potency to regulate T cell-mediated immune responses. However, their efficacy to regulate immunological responses in vivo remains unclear. Here, we report that repetitive intraperitoneal injection of recombinant Lewis rat-derived MHC class I antigens in Dark Agouti (DA) rats modulates alloreactivity. METHODS: RT1.A1 (Lewis derived) genes were cloned into mammalian expression vectors, and RT1.Aa (DA derived) genes were used to transfect a rat myeloma cell line. RT1.A1 molecules were injected intraperitoneally in DA recipients that subsequently underwent transplantation with Lewis-derived cardiac allografts. RESULTS: Soluble class I antigens were secreted by the transfected cells and were shown to be heterodimeric, peptide-loaded, and conformationally folded. Injection of donor derived soluble MHC significantly reduced the ability of recipient animals to mount a cytotoxic T-cell response to donor-derived tissue. More interestingly, this treatment significantly prolonged donor-graft survival and allowed 60% of treated animals to develop graft tolerance (>120 days), when donor sMHC were combined with a single subtherapeutic dosage of cyclosporine. Thymectomy of recipient animals before transplantation did not interfere with induction of peripheral tolerance. CONCLUSIONS: Donor-derived sMHC are potential tolerogens for down-regulating the cytotoxic T-cell response of animals that undergo transplantation. Thus, these data provide for the first time a rationale for the application of directly injected sMHC in vivo to down-regulate immunological responses and aid the induction of graft tolerance. PMID- 11773899 TI - Prolonged survival of xenograft fetal cardiomyocytes by adenovirus-mediated CTLA4 Ig expression. AB - BACKGROUND: Experimental allografting of fetal cardiomyocytes has been performed successfully. In this study, we attempted to transplant rat fetal cardiomyocytes into the hearts of mice by blocking the CD28/B7 costimulatory pathway via CTLA4 Ig gene transfer. METHODS: Fetal cardiomyocytes derived from Dark Agouti rat were infected with CTLA4-Ig-expressing adenovirus vectors (AdCTLA) and injected directly into the normal myocardium of C3H/He mice (n=15). For control, cells infected with beta-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). Mice were killed at 2 (n=5), 4 (n=5), and 8 (n=5) weeks after xenotransplantation. Transplanted fetal cardiomyocytes were examined for survival by immunostaining with anti-rat atrial natriuretic peptide and anti-CTLA4-Ig antibodies. RESULTS: Fetal cardiomyocytes were successfully infected by AdCTLA and AdRL. The cardiomyocytes infected with AdCTLA expressed CTLA4-Ig and survived to 8 weeks after xenotransplantation in all of these mice. However, cardiomyocytes infected with AdRL and noninfected cells were not detected even 2 weeks after xenotransplantation. CONCLUSION: Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression. PMID- 11773900 TI - Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience. AB - BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT. PMID- 11773901 TI - Progression of hepatic damage during cold storage after procurement in a liver and kidney donor with HELLP syndrome. AB - BACKGROUND: HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and acute fatty liver of pregnancy are associated with preeclampsia and fetal defects in fatty acid metabolism. This defect causes the accumulation of metabolites that are harmful to the maternal liver. CASE REPORT: We report a liver and kidney donor with HELLP syndrome and describe the progression of disease in the liver during cold storage. Before procurement, liver biopsy demonstrated minimal necrosis. However, after cold storage, repeat biopsy demonstrated more than 30% necrosis. The liver was not engrafted; the kidneys were transplanted without complication. CONCLUSION: Livers procured from patients with HELLP syndrome should be carefully evaluated for progression of hepatic damage during cold storage and transport. PMID- 11773902 TI - Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using right lobe graft. AB - BACKGROUND: Recently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft. METHODS: 3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donor's vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed. RESULTS: The 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis. CONCLUSIONS: 3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft. PMID- 11773903 TI - In vivo analysis of porcine endogenous retrovirus expression in transgenic pigs. AB - Xenotransplantation offers a potential solution to the shortage of donor organs for allotransplantation. In vitro studies that demonstrate the transmission of porcine endogenous retroviruses (PERV) from porcine cells to human cells and cell lines have raised concerns regarding the potential transmission of PERV to both xenograft recipients and their contacts (1-4). While no evidence of infection has been detected in any patients who have been treated with a variety of different porcine tissues (5-8), two studies have shown that severe combined immunodeficient (SCID) mice can be infected by PERV after the transplantation of porcine islets (9-10). To further address the concerns of PERV, expression of this virus in tissues and serum from transgenic pigs that express human decay accelerating factor was investigated. Although viral mRNA expression was detected in a variety of tissues, no evidence of viral release was observed in any of the porcine tissues analyzed by transmission electron microscopy. Analysis of porcine serum using the product-based reverse transcriptase assay suggested that virions may be present in porcine serum from large white pigs. However, using methods based on those previously described by Wilson et al. (4), infectious virus was not detected when activated peripheral blood mononuclear cells from these pigs were cocultivated with human cells known to be permissive for PERV. PMID- 11773904 TI - Are we asking too much of our trials? PMID- 11773905 TI - When young hearts are broken: profiles of premature myocardial infarction. PMID- 11773906 TI - Long QT syndrome: diagnosis and management. AB - BACKGROUND: Long QT syndrome (LQT) is characterized by prolongation of the QT interval, causing torsade de pointes and sudden cardiac death. The LQT is a disorder of cardiac repolarization caused by alterations in the transmembrane potassium and sodium currents. Congenital LQT is a disease of transmembrane ion channel proteins. Six genetic loci of the disease have been identified. Sporadic cases of the disease occur as a result of spontaneous mutations. The acquired causes of LQT include drugs, electrolyte imbalance, marked bradycardia, cocaine, organophosphorus compounds, subarachnoid hemorrhage, myocardial ischemia, protein sparing fasting, autonomic neuropathy, and human immunodeficiency virus disease. METHODS: Data on the diagnosis and management of LQT were thoroughly reviewed. RESULTS AND CONCLUSIONS: The diagnosis of LQT primarily rests on clinical and electrocardiographic features and family history. The clinical presentations range from dizziness to syncope and sudden death. Genetic screening is available primarily as a research tool. Short-term treatment of LQT is aimed at preventing the recurrences of torsades and includes intravenous magnesium and potassium administration, temporary cardiac pacing, withdrawal of the offending agent, correction of electrolyte imbalance, and, rarely, intravenous isoproterenol administration. The long-term treatment is aimed at reducing the QT-interval duration and preventing the torsades and sudden death and includes use of oral beta-adrenergic blockers, implantation of permanent pacemaker/cardioverter defibrillator, and left thoracic sympathectomy. Sodium channel blockers are promising agents under investigation. Electrocardiograms are recorded for screening of family members. The data favor treating asymptomatic patients, if <40 years old at the time of diagnosis, with beta-adrenergic blockers. PMID- 11773907 TI - Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics. AB - BACKGROUND: Many pediatric patients undergoing cardiac surgery involving cardiopulmonary bypass have a predictable fall in the cardiac index 6 to 18 hours after surgery, the so-called low cardiac output syndrome (LCOS). Because patients who have LCOS require more monitoring and support and have a prolonged stay in the intensive care unit, the syndrome is associated with a costly morbidity. Milrinone, a phosphodiesterase III inhibitor, improves cardiac muscle contractile force and vascular muscle relaxation through positive inotropic and vasodilatory effects. The purpose of the Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics (PRIMACORP) study is to evaluate the safety and efficacy of the prophylactic use of milrinone in pediatric patients at high risk for development of LCOS after undergoing cardiac surgery. METHODS: Patients in the multicenter, randomized, double-blind, placebo-controlled, parallel treatment study will be randomized to 1 of 3 treatment arms: (1) low-dose milrinone (25 microg/kg intravenous bolus over 60 minutes followed by a 0.25 microg/kg/min infusion for 35 hours), (2) high-dose milrinone (75 microg/kg intravenous bolus over 60 minutes followed by a 0.75 microg/kg/min infusion for 35 hours), or (3) placebo. RESULTS: The primary end point for efficacy evaluation will be based on a composite variable consisting of death or development of LCOS requiring additional mechanical or pharmacologic support, up to 36 hours after randomization. A 2-sided test with a 0.025 type I error will be used for the primary end point analysis. The PRIMACORP study will enroll a total of 240 patients. Six additional secondary end points will be analyzed. CONCLUSIONS: The PRIMACORP study will address several questions regarding the safety and efficacy of prophylactic milrinone use in pediatric patients at high risk for development of LCOS after cardiac surgery. PMID- 11773908 TI - Choice of clinical outcomes in randomized trials of heart failure therapies: disease-specific or overall outcomes? AB - BACKGROUND: There are different views regarding the appropriateness of using cause-specific events or all events as the primary outcome of clinical trials. METHODS: This is a methodologic essay in which we discuss the pros and cons of the 2 approaches and provide illustrative examples. RESULTS: Our preference is the use of cause-specific outcomes (as long as they can be classified with reasonable reproducibility and without bias) because they are more likely to be sensitive to change, less likely to lead to spurious conclusions by random variations in categories of outcomes that are unlikely to be affected by treatment, and relatively free from confounding. Overall benefit-risk ratios can be derived by examining the impact of treatment on various categories of outcomes and then developing a general judgment. Such an approach will also allow judgments to be made regarding generalizability of results across various groups of patients who are at differing risks for an event. CONCLUSIONS: In general, cause-specific outcomes sensitive to the effects of a treatment are to be preferred as the principal outcome in trials of heart failure, as long as they are biologically sensible and can be classified without bias. Other outcomes, not expected to be affected, should also be reported separately. PMID- 11773909 TI - Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure. AB - BACKGROUND: Although sodium restriction is considered essential in the management of patients with chronic heart failure (CHF), there are no data available regarding patients awareness of and ability to comply with the sodium restriction guideline. METHODS: Between May 1999 and August 2000, 50 patients referred to the Parkland Memorial Hospital CHF clinic were assessed by a registered dietitian for (1) awareness of the sodium restriction guideline, (2) ability to read the sodium content from a Nutrition Facts label, and (3) ability to sort 12 food containers, all bearing a Nutrition Facts label, into high- and low-sodium groups. A global measure of dietary sodium knowledge was calculated ("sodium knowledge score," range 0-10). These tests were repeated after the patient completed one or more educational sessions (mean 2.8 +/- 1.5) with the dietitian. RESULTS: The proportion of patients aware of the sodium restriction guideline was 14% at baseline and 42% at follow-up (P <.01). The proportion of patients able to read the sodium content from the Nutrition Facts label was 58% at baseline and 92% at follow-up (P <.01). The sodium knowledge score was 3.8 +/- 3.4 at baseline and 5.8 +/- 3.2 at follow-up (P <.01). The proportion of subjects who achieved a perfect sodium knowledge score of 10 was 8% at baseline and 26% at follow-up (P <.05). The number of food containers sorted accurately was 10.6 +/- 1.5 at baseline and 11.3 +/- 1.1 at follow-up, P =.09. CONCLUSIONS: On referral to a specialty CHF clinic, many patients had severe deficiencies in their knowledge base regarding dietary sodium intake that would preclude compliance with the sodium restriction guideline. Directed education focusing on sodium intake corrected many of these deficiencies. PMID- 11773910 TI - Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure. AB - BACKGROUND: Patients with heart failure frequently exhibit intraventricular conduction delays, which contribute to asynchronous contraction patterns and impaired hemodynamic performance. Cardiac resynchronization therapy (CRT) with biventricular (BV) and left ventricular (LV) pacing has been shown to improve both hemodynamic and clinical performance. This study investigated the effects of CRT on LV Doppler indices in these patients. METHODS AND RESULTS: Thirty-two patients with advanced heart failure (New York Heart Association class > or =III, QRS >120 milliseconds, PR interval >150 milliseconds) were studied 4 weeks after implantation of a CRT system. Doppler echocardiography was conducted in 3 separate CRT modes, right ventricular, LV, and BV stimulation at 3 different atrioventricular delays. CRT resulted in significant improvement of Doppler parameters such as filling time (FT, 313 +/- 111 milliseconds at baseline --> 363 +/- 154 milliseconds [BV], P <.05), aortic velocity time integral (AO(VTI) 23.2 +/- 7.4 cm at baseline --> 26.8 +/- 8.8 cm [LV], P <.05), and the myocardial performance index (MPI, 1.21 +/- 0.51 at baseline --> 0.85 +/- 0.34 [BV], P <.05). The most improvement was observed with LV and BV stimulation at short and intermediate atrioventricular delays (80-120 milliseconds), independent of ischemic or idiopathic origin. CONCLUSIONS: CRT improves hemodynamic performance in patients with heart failure with intraventricular conduction delays. Doppler echocardiography allows noninvasive evaluation of acute CRT effects in patients with heart failure. In particular, FT, AO(VTI), and MPI are useful parameters for noninvasive follow-up and optimization of pacing parameters. PMID- 11773911 TI - Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). AB - BACKGROUND: Congestive heart failure (HF) represents a major public health problem with an age-related increasing prevalence. Despite the high mortality and morbidity in elderly patients with HF, limited clinical and prognostic data are available for development of appropriate prevention and treatment strategies. METHODS: A cohort of 3327 outpatients consecutively enrolled in the Registry of Italian Network on Congestive Heart Failure by 133 cardiology centers was studied. Univariate and multivariate analyses were performed to compare patients <70 and > or =70 years old and to evaluate associations between clinical variables and the 1-year mortality rate and hospitalizations. RESULTS: With respect to the 2294 patients <70 years old, the 1033 (31%) elderly patients were significantly more likely to be female, to be in New York Heart Association (NYHA) class III-IV, and to have preserved left ventricular systolic function (ejection fraction >40%), an ischemic/valvular etiology, and atrial fibrillation/flutter. Elderly patients received angiotensin-converting enzyme inhibitors, beta-blockers, and anticoagulants less frequently than younger patients did. The 1-year mortality rate was significantly higher in patients > or =70 years old (22% vs 13.7%, P <.001). Age was an independent predictor of 1-year mortality, increasing 2.8% by each year of age. Independent predictors of 1-year mortality in elderly patients were (1) > or =1 hospital admission in the previous year (relative risk [RR] 2.09, 95% CI 1.51-2.87), (2) systolic blood pressure (RR 0.98, 95% CI 0.97-0.99), (3) NYHA class III-IV (RR 1.57, 95% CI 1.20-2.07), and (4) age (RR 1.028, 95% CI 1.001-1.056). CONCLUSIONS: Our study confirms that elderly patients (1) are seen in a more advanced stage of HF, (2) are less likely to receive evidence-based treatments, (3) show more frequently preserved systolic function, and (4) have a worse prognosis. Consequently, there is a need to develop more effective and targeted management strategies for this escalating health problem. PMID- 11773913 TI - Mode and timing of treatment failure (recurrent ischemic events) after hospital admission for non-ST segment elevation acute coronary syndromes. AB - BACKGROUND: Clarification of the specific clinical course of non-ST-segment elevation acute coronary syndromes (NSTEMI ACS), including recurrent ischemic events and need for coronary revascularization, is important given the increasing economic pressure to shorten the length of hospitalization and therefore the duration of acute therapy. To examine the mode and timing of subsequent cardiac events, we analyzed pooled data from the ESSENCE and TIMI 11B studies of antithrombotic therapy in NSTEMI ACS. METHODS: The daily event rates (with confidence intervals) during the first 43 days and the monthly average event rates during the first year were tabulated for 7081 patients. RESULTS: The median antithrombotic treatment duration was 3.2 days, whereas the highest absolute frequency of recurrent angina prompting urgent revascularization, myocardial infarction, or death after hospital admission occurred on day 2, day 3, and day 8, respectively. Coronary revascularization was performed in 32% of patients, with the greatest number occurring on day 4. Only 12% of the end point events were adjudicated as being periprocedural. The median length of hospital stay was 7 days. CONCLUSIONS: Despite aggressive antithrombotic therapy, a significant proportion of patients with NSTEMI ACS have recurrent ischemia precipitating urgent revascularization or infarction within the first few days, whereas the highest risk of death occurs later, after the first week. PMID- 11773912 TI - Acute myocardial infarction in the young--The University of Michigan experience. AB - BACKGROUND: The purpose of this study was to assess frequency, risk factors, treatment, and complications of very young patients with acute myocardial infarction (MI) at the University of Michigan Medical Center (UMMC). METHODS: From a database of 976 consecutive patients admitted to the UMMC with acute MI between 1995 and 1998, we compared care and outcomes of patients divided into 3 age categories: <46 years, 46-54 years, and >54 years. Risk factors, presenting symptoms, type of MI, management, complications, and hospital outcomes of the 3 groups were evaluated. RESULTS: Young patients represented >10% of all patients with acute MI, and >25% of these individuals were women, a number considerably higher than seen in previous studies. This group of young patients was more likely to have Q-wave MI and risk factors such as family history and tobacco use and less likely to have a history of angina. Although all 3 groups received similar inpatient treatment, there was more attention paid to risk factor modification such as smoking cessation and referral to cardiac rehabilitation in younger individuals. Young patients had fewer in-hospital complications and a lower mortality rate. CONCLUSIONS: At the University of Michigan, >1 in 10 with acute MI is <46 years old. Data suggest that current management and aggressive risk factor modification are quite good in this particular group, and overall the mortality rate is very low. PMID- 11773914 TI - Incidence of high-risk acute coronary syndromes and eligibility for glycoprotein IIb/IIIa inhibitors among patients admitted for possible myocardial ischemia. AB - OBJECTIVE: Recent studies have demonstrated that glycoprotein (GP) IIb/IIIa inhibitors can reduce cardiac events in patients with acute coronary syndromes (ACS). However, little is known about how many patients are actually eligible for treatment. Our purpose was to determine how many patients admitted for possible myocardial infarction (MI) meet GP IIb/IIIa inhibitor treatment criteria. METHODS: Patients admitted for possible MI who underwent a standard protocol that included serial sampling of total creatine kinase (CK), CK-MB, and troponin I (TnI) were retrospectively assigned to different treatment algorithms on the basis of criteria from GP IIb/IIIa inhibitor trials: an electrocardiogram (ECG) consistent with acute MI or ischemia, and myocardial marker elevations. Elevated CK-MB was considered diagnostic of MI. High-risk ACS was defined as ischemic ECG changes or troponin elevations without CK-MB elevations. RESULTS: A total of 2179 patients were admitted for MI exclusion. MI was identified in 304 patients (14.0%) (123 ST-elevation, 49 ischemic ECG, 132 nonischemic ECG). Another 273 patients (12.5%) without CK-MB criteria for MI met high-risk ACS criteria (172 ischemic ECG, 120 TnI elevations). Ischemic ECGs or elevated myocardial markers identified 454 (21%) patients as eligible for treatment. Inclusion of patients with ST elevation increased eligibility to 26.5%. Of the 454 non-ST-elevation ACS patients, 340 (74%) were identified early by the ECG or the initial markers. CONCLUSIONS: A large proportion of patients admitted for possible MI met criteria for treatment with GP IIb/IIIa inhibitors. The non-ST-elevation ACS group was >3 times larger than the ST-elevation MI group. These findings have important implications for treatment of patients with ACS. PMID- 11773915 TI - Reduced inhibition by abciximab in platelets with the PlA2 polymorphism. AB - BACKGROUND: The PlA2 polymorphism of the glycoprotein IIb/IIIa (fibrinogen) receptor has been associated with increased restenosis and stent thrombosis. We postulated that this allele could alter the antiplatelet effect of abciximab in patients undergoing percutaneous coronary intervention. METHODS: Optical platelet aggregation assays, Ultegra (Accumetrics, San Diego) rapid platelet function assays, and radiometric abciximab binding assays were performed in 66 Pl(A1/A1) and 21 PlA1/A2 patients undergoing percutaneous coronary interventions. The affinity of abciximab for the PlA1 and PlA2 receptors was determined with use of transfected cells. RESULTS: Compared with PlA1/A1 homozygotes, PlA1/A2 platelets were less completely inhibited after abciximab bolus (P =.002) and at 24 hours (P =.02) as assessed by the rapid platelet function assays. Optical aggregation assays confirmed that Pl(A1/A2) platelets were less completely inhibited after abciximab bolus (P =.05). The radiometric abciximab binding assay demonstrated that the PlA1/A2 platelets had fewer baseline fibrinogen receptors than did the PlA1/A1 platelets (P =.04) and more free fibrinogen receptors at 24 hours (P =.008). Cells transfected to express homozygous PlA1 or PlA2 demonstrated a nonsignificant trend (P =.12) for reduced abciximab affinity for PlA2. CONCLUSIONS: PlA1/A2 platelets are less completely inhibited with abciximab, contributing to the observed interindividual variability in platelet function inhibition. Because the extent of platelet inhibition is an independent predictor for the risk of major adverse coronary events after percutaneous coronary intervention, the relative resistance of PlA2-positive platelets may contribute to a less favorable outcome in these patients. PMID- 11773916 TI - Effect of cigar smoking on endothelium-dependent brachial artery dilation in healthy young adults. AB - BACKGROUND: Cigar smoking has become a quickly growing trend among teenagers, women, and young adults. The objective was to explore whether cigar smoking affects flow-mediated vasodilation in healthy, non-smoking young adults. METHODS: This was a prospective randomized trial with open design. It was performed in a cardiology teaching program in a private community hospital that serves as a major referral center within the greater Miami area. Apparently healthy, non smoking young adult cardiology trainees and staff between the ages of 20 and 45 years were randomly assigned to a cigar smoking group (n = 15) or a control group (n = 14). The main outcome measures were the difference in percent diameter increase in the brachial artery after reactive hyperemia and sublingual nitroglycerin between members of the cigar smoking and control groups at baseline, measured after cigar smoking, and at 5 hours. RESULTS: Twenty-nine participants were randomized. Percent diameter increase in the brachial artery was measured with the use of high-resolution ultrasonography. Baseline percent diameter increase after reactive hyperemia and sublingual nitroglycerin was similar in both groups (6.2% vs 6.7%, P = .4 and 22% vs 23%, P = .5, respectively). We observed a 2.5% increase in brachial artery diameter with hyperemia after cigar smoking compared with a 9.4% increase in the control group, P = .045. Values after nitroglycerin were similar between groups, P = .2. Between group analysis showed no significant difference in percent dilation after reactive hyperemia at 5 hours, P = .4, but a significant difference was seen after sublingual nitroglycerin, P = .02. CONCLUSIONS: These data are compatible with the possibility that cigar smoking may have an acute effect on endothelium dependent, flow-mediated brachial artery dilation and do not support the possibility of an immediate effect on endothelium-independent vasodilation. Taken together, these results suggest that cigars are not an innocuous alternative to cigarette smoking. PMID- 11773917 TI - Pharmacodynamic profile of short-term readministration of abciximab in healthy subjects. AB - OBJECTIVE: The purpose of the study was to establish a rebolus regimen for abciximab that restores pharmacologic glycoprotein (GP) IIb/IIIa receptor blockade within a short time frame (up to 48 hours) after completion of an initial treatment. METHODS AND RESULTS: The study was a single-center, nonrandomized, open-label dose escalation trial in healthy volunteers (n = 30). Each subject received a 0.25 mg/kg bolus and a 0.125 microg/kg per minute infusion of abciximab, followed by incremental bolus doses of the agent at 15 minute intervals up to 48 hours (10 per group) after completion of the infusion, (maximal cumulative rebolus dose of 0.25 mg/kg). Pharmacodynamic measurements (GP IIb/IIIa receptor blockade, turbidimetric and whole blood platelet aggregation with use of a rapid platelet function assay [RPFA]) were obtained at periodic intervals during and after administration of the abciximab bolus and infusion. At the time of the first rebolus, pharmacodynamic measurements were attained immediately before administration of each rebolus and 15 minutes after the last rebolus dose. In subjects who received reboluses 12 hours after infusion, a cumulative dose of 0.05 mg/kg restored >80% blockade of GP IIb/IIIa receptors and >80% inhibition of turbidimetric (5 and 20 micromol/L adenosine diphosphate) and RPFA aggregation in 10 of 10 subjects. At 24 hours after treatment, a cumulative abciximab bolus dose of 0.1 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. At 48 hours after treatment, a cumulative bolus dose of 0.15 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. CONCLUSIONS: A fraction of the bolus of abciximab restored pharmacologic (>80%) GP IIb/IIIa receptor blockade when readministered at various postinfusion time points. These observations suggest that in the setting where acute readministration of abciximab is required less than a full bolus dose of the agent is warranted. PMID- 11773918 TI - Multicenter, dose-ranging study of efegatran sulfate versus heparin with thrombolysis for acute myocardial infarction: The Promotion of Reperfusion in Myocardial Infarction Evolution (PRIME) trial. AB - BACKGROUND: Adjunctive therapies that increase the incidence of normal reperfusion after thrombolysis for acute myocardial infarction (MI) could enhance clinical outcomes. Direct thrombin inhibitors may offer an advantage over standard adjunctive therapies. METHODS: We randomized 336 patients with acute MI at 33 sites to receive 1 of 5 doses of efegatran sulfate, a direct thrombin inhibitor, or heparin for 72 to 96 hours, both with accelerated alteplase and aspirin. The primary end point was the incidence of thrombolytic failure (death, reinfarction, or TIMI grade 0-2 flow in the infarct artery from 90 minutes to discharge or 30 days, whichever occurred earlier). RESULTS: Significantly more patients randomized to efegatran had evidence of heart failure at admission. The lowest-dose efegatran arm was terminated at 15 patients because of unacceptably increased thrombolytic failure. The primary end point occurred in 53.0% of patients treated with heparin, in 53.8% of patients treated with efegatran overall (P =.90), and in 55.4% of patients given intermediate-dose efegatran (P =.74). These findings were unaffected after adjustment was done for baseline differences. Most bleeding was minor; major bleeding and the use of blood transfusions did not differ significantly by treatment. Three patients in the high-dose efegatran group had intracranial hemorrhage, as did 1 patient in the heparin group. Continuous ST monitoring showed a shorter time to recovery for the efegatran group (median 107 minutes) compared with the heparin group (154 minutes; P =.025). CONCLUSIONS: Efegatran sulfate appeared to offer no clear advantage over heparin as an adjunct to thrombolysis for acute myocardial infarction, although there may be a modest improvement in time to reperfusion. PMID- 11773919 TI - Relationship of creatine kinase-myocardial band release to Thrombolysis in Myocardial Infarction perfusion grade after intracoronary stent placement: an ESPRIT substudy. AB - BACKGROUND: The etiology of creatine kinase-myocardial band (CK-MB) release after percutaneous coronary intervention (PCI) remains unclear. The goal of this study was to evaluate the relationship of both epicardial and tissue level perfusion at the completion of stent placement to CK-MB release after the procedure. Given the high rates of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after PCI, we hypothesized that abnormalities in tissue level perfusion would instead explain CK-MB release. METHODS: Data were drawn from the angiographic substudy of the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial of eptifibatide versus placebo in patients undergoing planned coronary stent implantation. In the substudy, cinefilms of 65 patients were analyzed by an angiographic core laboratory blinded to enzymatic and clinical outcomes. RESULTS: The release of CK-MB was not associated with TIMI grade 3 flow or the corrected TIMI frame count; 100% of patients had TIMI grade 3 flow at the completion of PCI. In contrast, tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) was related to postintervention CK-MB release: patients with a closed myocardium (TMPG 0/1) or delayed myocardial perfusion (TMPG 2) had an average CK-MB release 2.2 +/- 2.7 times the upper limit of normal (n = 34), whereas those patients with normal myocardial perfusion (TMPG 3, n = 24) had CK-MB 0.8 +/- 0.6 times the upper limit of normal (P =.01). Although no patients with TMPG 3 sustained death/myocardial infarction/urgent target vessel revascularization or thrombotic bailout, 17.7% of patients with TMPG 0/1/2 did by 48 hours (P =.037). CONCLUSIONS: Impaired tissue level perfusion as assessed by the TMPG and not epicardial coronary blood flow is associated with CK-MB elevation after PCI. These data provide a pathophysiologic link between impaired tissue level perfusion, post-PCI infarction, and adverse clinical outcomes. PMID- 11773920 TI - Revascularization improves survival in ischemic cardiomyopathy regardless of electrocardiographic criteria for prior small-to-medium myocardial infarcts. AB - BACKGROUND: The purpose of the current study was to determine whether survival after revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) is influenced by the extent of electrocardiographic (ECG) evidence of previous myocardial infarction (MI) in patients with ischemic cardiomyopathy by use of the 50-criteria, 31-point Selvester QRS scoring system. METHODS: Patients with ischemic cardiomyopathy documented by a left ventricular ejection fraction (LVEF) < or =30% undergoing coronary angiography between January 1984 and July 1996, with no acute MI within the last 30 days, follow-up through 1996, and > or =75% occlusion in at least 1 major coronary artery at catheterization were included. These patients were subdivided on the basis of subsequent treatment: revascularization or no revascularization. The complete Selvester QRS system was applied to each patient's ECG and the subgroups were further subdivided by QRS score. RESULTS: The 141 patients receiving revascularization had better survival at 5 years compared with the 298 patients receiving no revascularization (adjusted 5-year survival rate 73% vs 47%, P =.0001). No significant treatment differences were observed for low (< or =3 points) versus high (>3 points) QRS levels in either of the 2 treatment groups (revascularized patients: P =.215, patients without revascularization: P =.126) between the 2 treatment groups. Although all patients had LVEF < or =30%, only 8% of patients had QRS scores >10 points, the level that would be expected if the decrease in LVEF could be attributed entirely to infarcted myocardium. CONCLUSIONS: Hibernating myocardium may contribute significantly to the decreased function in patients with ischemic cardiomyopathy, and the QRS score cannot be used as an independent predictor of survival in those patients with a marked decrease in LVEF but small to moderate infarct sizes. PMID- 11773922 TI - Six-month outcomes of percutaneous transluminal coronary angioplasty in hypertensive patients: results from the ROSETTA registry. Routine Versus Selective Exercise Treadmill Testing After Angioplasty. AB - PURPOSE: Hypertension is an important risk factor for coronary artery disease. However, the impact of hypertension on the outcomes of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is unknown. Our purpose was to evaluate the association between hypertension and adverse outcomes and repeat cardiac procedures during the 6-month period after PTCA. METHODS: We studied 791 patients who were enrolled in the Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) registry. This registry is a prospective multicenter study examining the use of functional testing after a successful PTCA. RESULTS: We compared 411 hypertensive patients (mean age 60.1 +/- 10 years, 31.1% female) with 380 normotensive patients (mean age 59.1 +/- 12 years, 16.2% female). Patients with hypertension had a higher 6-month rate of composite clinical events (unstable angina, myocardial infarction, death) than did normotensive patients (16.5% vs 10.5%, P =.017). In addition, there was a trend for hypertensive patients to have higher rates of cardiac procedures (angiography, repeat PTCA, coronary artery bypass graft surgery) compared with normotensive patients (19.8% vs 14.9%, P =.074). However, functional testing after PTCA was lower among hypertensive subjects (44.4% vs 54.0%, P =.008). Among the 411 hypertensive patients, a regression analysis showed that several variables were independently associated with increased 6-month adverse event rates, including pre-PTCA Killip class III-IV (odds ratio [OR] 5.7, 95% CI 1.7 19.0), Canadian Cardiovascular Society angina class III-IV (OR 2.1, 95% CI 1.1 4.2), unstable angina as the reason for PTCA (OR 2.3, 95% CI 1.2-4.3), peripheral vascular disease (OR 3.2, 95% CI 1.5-6.4), PTCA of a bypass graft (OR 3.1, 95% CI 1.2-7.6), and calcium antagonist usage at admission for the index PTCA (OR 1.9, 95% CI 1.1-3.4). CONCLUSIONS: During the 6-month period after a successful PTCA, patients with hypertension have significantly higher adverse event rates than do those without hypertension. Several clinical variables may help identify which hypertensive patients are at higher risk for clinical events. PMID- 11773921 TI - Effect of 300- and 450-mg clopidogrel loading doses on membrane and soluble P selectin in patients undergoing coronary stent implantation. AB - BACKGROUND: After coronary artery stent implantation patients are treated with the adenosine diphosphatase (ADP) receptor antagonist clopidogrel to prevent subacute stent thromboses. Today these patients initially receive a loading dose of 300 mg of clopidogrel to accelerate the complete drug effect. In the current study we investigated whether a higher loading dose can shorten the time until the maximum platelet inhibitory effect of clopidogrel is achieved. METHODS: P selectin expression of nonstimulated and ADP-stimulated platelets was flow cytometrically measured before the clopidogrel loading dose and on 3 consecutive days in 52 patients with coronary artery disease: 21 patients in group 1 received 300 mg of clopidogrel after stent implantation and 11 patients in group 2 received the higher 450-mg clopidogrel loading dose followed by a daily dose of 75 mg of clopidogrel for both groups. The control group consisted of 20 patients who were monitored over 2 days before coronary intervention. Soluble P-selectin levels in plasma were determined by an enzyme-linked immunosorbent assay. RESULTS: Inducible P-selectin expression on ADP-stimulated platelets was significantly reduced (P =.05) on days 1 and 2 in patient group 2 (450-mg loading dose) compared with group 1 (300-mg loading dose). No influence of clopidogrel on the P-selectin levels in plasma was observed. CONCLUSIONS: In our study the application of 450 mg of clopidogrel as the loading dose in patients undergoing coronary stenting shortens the period until the maximum effect of the ADP receptor antagonist is achieved and thus may lead to a more successful prevention of subacute coronary stent thromboses. PMID- 11773923 TI - Variability in cost of coronary bypass surgery in New York State: potential for cost savings. AB - OBJECTIVE: Previous analyses of variability in bypass resource use have not focused on hospital-level variation or adequately explored the influence of patient risk. We combined a clinical database with claims data to fully characterize patient level and hospital level variability in bypass surgery cost and length of stay in New York State and explored the extent to which lower cost is associated with worse quality of care. METHODS: By use of 1992 clinical and claims data, we identified by multivariable regression which patient characteristics influence bypass cost and length of stay. Hospital was then incorporated as a random variable in mixed linear models to determine its impact on resource use. The relationship between risk-adjusted in-hospital mortality and cost was then explored. RESULTS: In the 21 hospitals for which cost data were available, mean leveled cost (exclusive of professional fees and noncomparable costs) was $15,713, with a mean length of stay of 14 days (n = 12,087). One fifth of the variation in resource use was explained by baseline patient risk. After adjustment for patient risk, hospital explained an additional 42% of variation in cost and an additional 8% of variation in length of stay. Among hospitals, risk adjusted cost varied almost 3-fold and risk-adjusted length of stay varied 50%. There was no association between cost and in-hospital mortality. CONCLUSIONS: As of 1992, there was considerable interhospital variability in bypass surgery cost after patient baseline risk was accounted for. This suggests that reductions in bypass cost could be achieved by normalizing clinical practice. PMID- 11773924 TI - Does enrollment in a randomized clinical trial lead to a higher cost of routine care? AB - BACKGROUND: Reimbursement for the routine care of patients enrolled in clinical trials is controversial. Our objective was to determine the added medical costs, if any, associated with enrollment in a randomized clinical trial. METHODS: We analyzed data from the Myocardial Infarction Triage and Intervention (MITI) Trial (1988-1991) and the registry of all patients admitted to 19 Seattle area coronary care units (1988-1993). The major trial entry criteria were age 35 to 71 years, symptom duration 15 minutes to 6 hours, and acute myocardial infarction on electrocardiogram. The trial group consisted of 264 of 324 randomized patients who received thrombolytics and had available cost data. From 11,932 registry patients, we identified a control group who met trial entry criteria but who were not enrolled because of logistic barriers or presentation outside the trial enrollment period, 335 of whom received thrombolytics and had available cost data. The groups were compared for total cost for initial hospitalization, with and without multivariable adjustment for baseline characteristics. RESULTS: Total hospital cost was not different between trial patients (median $11,516) and control subjects (median $14,200) (trial/control mean cost ratio 0.91 [95% CI 0.82-1.02]). Participation in the trial had an insignificant effect on costs in the multivariable model (cost ratio 1.04, 95% CI 0.95-1.16). Significant predictors of cost included hospital of admission, length of stay, and coronary revascularization procedures. CONCLUSION: Participation in the MITI randomized trial had no effect on the cost of routine care. PMID- 11773925 TI - Benefits of an "angina clinic" for patients with coronary artery disease: a demonstration of health status measures as markers of health care quality. AB - OBJECTIVE: Our purpose was to determine the efficacy of health status measurement in quantifying improvements in quality of care provided by an "angina clinic." STUDY DESIGN: In a pretest-posttest, nonequivalent control group design in the outpatient clinics of a Veterans Affairs Medical Center, 535 patients with coronary disease were followed up, without intervention, for 3 months and were defined as the "usual-care" group. Concurrently, a clinical trial that optimized the antianginal medications of 100 patients with chronic, stable coronary disease was conducted and defined as the "angina clinic" group. The 3-month change in scores for the Seattle Angina Questionnaire, a valid, reliable, and responsive disease-specific health status measure for patients with coronary disease, was used as the main outcome measure. RESULTS: After baseline differences between groups were controlled, the "angina clinic" conferred substantial improvement on patient symptom control (3-month benefit in angina frequency +9.4, P <.001; in angina stability +14.7, P <.001), treatment satisfaction (+8.6, P <.001), quality of life (+6.8, P <.001), and physical limitations resulting from coronary disease (+3.6, P =.047). Only the changes in physical limitation were not clinically significant. CONCLUSION: Disease-specific health status measures can provide valuable insights into the quality of care associated with innovations in health care delivery. These results suggest that patients in a clinical trial optimizing antianginal medications had greater improvements in symptom control, treatment satisfaction, and quality of life compared with similar patients receiving "usual care" in a general medicine clinic. PMID- 11773926 TI - Determinants of disability in older coronary patients. AB - BACKGROUND: Patient-reported physical function is a major component of disability determinations and an important contributor to health-related quality of life. Prior studies of coronary disability have shown a surprisingly poor correlation between real-life activity profile and exercise capacity measured on the treadmill. The goal of the current investigation was to evaluate the relative importance of medical factors, sex, fitness-related measures, and psychologic factors as determinants of patient-reported physical function score in older persons with established coronary heart disease (CHD). METHODS: Determinants of disability were studied in 51 community-dwelling patients >65 years old (71 +/- 5 years, range 65-83 years) with established chronic CHD. Patient-reported physical function score (scaled 0-100) was measured by the Medical Outcomes Study Short Form physical function section. Independent variables included clinical and demographic data, treadmill testing, rest and exercise echocardiography, measures of body composition, strength, aerobic fitness, and a depression score. RESULTS: Patients with a diagnosis of myocardial infarction had a lower physical function score than did patients with other CHD diagnoses (68 +/- 19 vs 82 +/- 22, P <.05). Univariate predictors of patient-reported physical function score included peak aerobic capacity (R = 0.62), treadmill test duration (R = 0.61), depression score (R = -0.60), handgrip strength (R = 0.42), and comorbidity score (R = 0.39). Peak aerobic capacity (R2 = 0.38) and depression score (cumulative R2 = 0.60) were the best independent predictors of physical function. Women had lower physical function scores than men (64 +/- 22 vs 78 +/- 20, P <.05) despite a similar age, diagnostic distribution, depression score, and comorbidity score. Resting left ventricular ejection fraction was not a predictor of physical function score. CONCLUSIONS: Peak aerobic capacity and depression score were the best independent predictors of patient-reported physical function score in older coronary patients. These data focus on the potential for exercise training and treatment of mental depression to prevent and treat coronary disability in older coronary patients. PMID- 11773927 TI - Assessment of cardiac viability by thallium 201 redistribution and dobutamine echocardiography. AB - OBJECTIVE: Dobutamine echocardiography and thalium 201 are useful in the assessment of myocardial viability, but both techniques frequently yield conflicting results. The objective of this study was to determine the minimum mass of viable myocardium that each test could detect and compare the agreement of dobutamine echocardiography and thallium 201 to detect viability. METHODS: Dobutamine echocardiography and thallium 201 were performed in 10 patients scheduled for cardiac transplantation. In each patient, 15 segments were studied. After transplantation these segments were analyzed by the pathologist measuring by a computer system the total area of each segment, the necrotic + fatty mass, and area (%) of viable myocytes per segment. The percentage of viable tissue was estimated ([Total mass - (Necrotic + Fatty tissue)]/Total mass x 100) on each segment, which was compared with the result (viable or not viable) obtained by echocardiography or thallium 201. RESULTS: Dobutamine echocardiography defined 90 segments (60%) as viable versus 117 (78%) in thallium (kappa 0.49, 95% CI 0.36 0.63). The minimum percent of viable tissue per segment defined as viable by thallium was 43% versus 49% by echocardiography. With use of thallium, the highest accuracy of the test to detect viability was when the percent of necrotic tissue of the segment analyzed was 40% (positive and negative likelihood ratio 2.2 and 3.6, respectively). By use of echocardiography, the highest accuracy of the test was observed when the percent of necrotic tissue of the segment analyzed was 31% (positive and negative likelihood ratio 5.5 and 7.7, respectively). CONCLUSION: The discrepant results of dobutamine echocardiography and thallium 201 are due to differences in the minimum mass of live myocytes required by each technique to detect viability. PMID- 11773928 TI - Prognostic value of a negative stress echocardiographic study in diabetic patients. AB - BACKGROUND: Diabetic patients have increased cardiovascular morbidity and mortality. We compared the long-term prognostic value of a negative, nonischemic stress echocardiogram in patients with and without diabetes. METHODS: Two hundred thirty-six consecutive subjects who had stress echocardiography and who were negative for inducible ischemia were included in the study. Baseline cardiac risk factors and cardiac events (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were identified. RESULTS: Follow-up was obtained in 233 subjects for a mean duration of 25 months. There were 144 nondiabetic and 89 diabetic patients. At baseline, the diabetic group had a significantly higher incidence of hypertension, hyperlipidemia, and history of coronary artery disease but had a lower incidence of smoking (P <.05). Diabetic patients had a significantly higher incidence of cardiac events (19% vs 9.7%, P =.03) and worse event-free survival (P =.03). There were more nonfatal myocardial infarctions in the diabetic group (6.7% vs 1.4%, P <.05) and a trend toward a higher proportion of hard events (myocardial infarction and cardiac death) in diabetic patients (12.4% vs 5.6%, P =.11). The hard event rate per year of follow-up was 2.7% in nondiabetic and 6.0% in diabetic patients. In diabetic patients, a history of coronary artery disease was the only predictor of cardiac events (R = 0.18, P <.05). CONCLUSION: Compared with nondiabetic patients, diabetic patients with negative stress echocardiograms are at greater risk for cardiac events. This appears to be due to a higher prevalence of established coronary disease in diabetic patients. PMID- 11773929 TI - Influence of left ventricular size and hemodynamics on the systolic longitudinal myocardial Doppler velocity response to stress. AB - BACKGROUND: Systolic myocardial Doppler velocity accurately identifies coronary artery disease. However, these velocities may be affected by age, hemodynamic responses to stress, and left ventricular cavity size. We sought to examine the influences of these variables on myocardial velocity during dobutamine stress in patients with normal wall motion. METHODS: One hundred seventy-nine consecutive patients with normal dobutamine echocardiograms were studied. Color myocardial tissue Doppler data were obtained at rest and peak stress, and peak systolic myocardial velocity (PSV) was measured in all basal and midventricular segments. Velocities at rest and peak stress were compared with left ventricular diastolic and systolic volumes, blood pressure, heart rate, and age by Pearson correlation and interdecile analysis by use of analysis of variance. RESULTS: The only clinical variable correlating with velocity was age; PSV showed only mild correlation with age at rest (r2 = 0.01, P =.001) and peak stress (r2 = 0.02, P =.001), but the normal peak velocity was significantly different between the extremes of age (<44 years and >74 years). There was very weak correlation of PSV with systolic and diastolic blood pressure (r2 < 0.01), heart rate (r2 < 0.01), systemic vascular resistance (r2 = 0.08), and left ventricular volumes (r2 < 0.01). CONCLUSIONS: Peak systolic velocity during dobutamine stress is relatively independent of hemodynamic factors and left ventricular cavity size. The extremes of age may influence peak systolic Doppler velocities. These results suggest that peak systolic velocity may be a robust quantitative measure during dobutamine echocardiography across most patient subgroups. PMID- 11773930 TI - Clinical and electrophysiologic effects of calcium channel blockers in patients receiving ibutilide. AB - BACKGROUND: Ibutilide is indicated for the acute termination of atrial fibrillation and atrial flutter. Recent work concludes that ibutilide activates a late inward sodium current that is blocked by nifedipine. Because calcium channel blockers are commonly used in patients with atrial fibrillation, it is important to exclude an antagonistic effect on ibutilide in the clinical setting. METHODS: We performed a retrospective electrocardiographic (ECG) review of patients enrolled in 3 clinical trials of ibutilide (2 atrial fibrillation conversion protocols and 1 ventricular tachycardia suppression protocol) to determine clinical efficacy and ECG effects of ibutilide in patients receiving and not receiving calcium channel blockers. Calcium channel blockers were administered as clinically indicated. A meta-analysis of the effects of calcium channel blockers on the conversion efficacy of atrial fibrillation and atrial flutter by ibutilide was also performed for studies in the literature. RESULTS: One hundred thirty patients were included in the ECG analysis (106 from atrial fibrillation protocols and 24 from the ventricular tachycardia protocol). Sixty-eight of the 130 patients were taking calcium channel blockers at the time of ibutilide administration. There were no differences in the QT or QTc intervals, conversion rate for atrial fibrillation or atrial flutter, or suppression of ventricular tachycardia between patients taking and not taking calcium channel blockers. In the meta-analysis of 4 studies, there was no difference in the conversion rates between patients taking (52%, n = 221) and not taking (45%, n = 402) calcium channel blockers (P =.09). CONCLUSIONS: In the clinical setting, the concomitant use of calcium channel blockers does not alter the ECG effects or efficacy of ibutilide for the treatment of atrial or ventricular arrhythmias. PMID- 11773931 TI - The relative importance of left atrial function versus dimension in predicting atrial fibrillation after coronary artery bypass graft surgery. AB - BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. The purpose of this study was to determine whether pre-existing left atrial dysfunction is a predictor of postoperative AF compared with other clinical predictors. METHODS: Ninety-three patients undergoing CABG were prospectively studied. Intraoperatively, transesophageal echocardiography was performed to measure left atrial size, transmitral flow velocity, and other routine parameters. Left atrial function was estimated by the following formula: Atrial index = Transmitral VTI total x LAEF/Left atrial maximal area (where VTI = velocity time integral of E and A waves, LAEF = left atrial ejection fraction). The association of potential clinical predictors with the occurrence of postoperative AF was evaluated by chi2 or Fisher exact tests, followed by stepwise multivariate logistic regression model. P values and odds ratios (OR) with 95% CIs were reported. Significance was set at P <.05. RESULTS: Postoperative AF occurred in 28 of 93 patients (30.1%). Patients with postoperative AF were older (67.0 +/- 8.3 vs 61.5 +/- 9.6 years, P =.0075), had larger left atrial maximal area (14.3 +/- 4.6 cm(2) vs 10.9 +/- 4.3 cm2, P <.001), lower atrial index (0.54 +/- 0.56 vs 0.82 +/- 0.64, P =.008), larger body surface area (BSA) (OR 57, 95% CI 3.97-827), longer aortic cross-clamp time (OR 1.03, 95% CI 1.00-1.05), and more likely to have a postoperative myocardial infarction (OR 3.28, 95% CI 0.99-10.87) compared with those without AF. By multivariate analysis, only age (OR 1.11, 95% CI 1.04-1.19, P =.002) and atrial dimension (OR 1.75, 95% CI 1.03-2.96, P =.038) were significant independent predictors of postoperative AF. Body surface area also increased the odds of postoperative AF, but the CI was wide (OR 114, 95% CI 4.65-2810, P =.004). CONCLUSIONS: Our results demonstrate that age and atrial enlargement, rather than atrial function, were independent predictors of postoperative AF. PMID- 11773932 TI - Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice. AB - BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty. PMID- 11773933 TI - Physician workforce in the cardiovascular sciences. PMID- 11773934 TI - Congestive heart failure: A national priority. PMID- 11773935 TI - Of old adversaries. PMID- 11773936 TI - The 2000 Canadian recommendations for the management of hypertension: part two- diagnosis and assessment of people with high blood pressure. AB - OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults. OPTIONS: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension. Out-of-clinic blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: People at increased risk of adverse cardiovascular outcomes and were identified and quantified. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian recommendations for the management of hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the identification of people at increased risk of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: The identification of people at higher risk of cardiovascular disease will permit counselling for lifestyle manoeuvres and the introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to aspects of the diagnosis and assessment of patients with hypertension, including the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, routine and optional laboratory testing, assessment for renovascular hypertension, home and ambulatory blood pressure monitoring, and the role of echocardiography in hypertension. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only the recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually. ENDORSEMENT: These recommendations are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control of Health Canada. PMID- 11773937 TI - Familial aggregation of seven-year changes in blood pressure in Canada. AB - OBJECTIVE: To determine the familial resemblance for baseline and seven-year changes in blood pressure in the Canadian population. METHODS: The study participants were 857 people from 348 families in the 1988 Campbell's Survey, which was a seven-year follow-up of the Canada Fitness Survey. Systolic and diastolic blood pressures were measured at baseline and at follow-up, and were adjusted for age and body mass index by using regression analysis. Familial correlation models were fit to the data by using path analysis, and maximal heritabilities were calculated from the most parsimonious models. RESULTS: There was significant familial resemblance for baseline blood pressure and changes in blood pressure. In general, all classes of familial correlations (spousal, parent offspring and sibling) were significant and were of comparable magnitude. The maximal heritabilities, which are influenced to an unknown degree by genes and shared environmental factors, were 50% and 70% for diastolic and systolic blood pressures, respectively, and 66% and 41% for seven-year changes in diastolic and systolic blood pressures, respectively. CONCLUSIONS: There is significant familial aggregation for blood pressure and for natural changes in blood pressure in the Canadian population. Genes may be important in explaining the familial resemblance for blood pressure; however, the presence of significant spousal correlations suggests that shared lifestyle and family environments are also important factors in the familial aggregation. PMID- 11773938 TI - Building capacity for awareness and risk factor identification in the community: the blood pressure assessment program of the Calgary Fire Department. AB - In 1995, the Calgary Fire Department developed a program to assess blood pressure in community fire stations, selected businesses and public venues. The program has gradually expanded. Currently, all 30 fire stations across Calgary, Alberta assess blood pressures for the public seven days per week throughout the year. Since 1995, there have been 10,883 measurements in 3477 people. Most people (2106) assessed had hypertensive readings, and 72 had readings greater than 220 mmHg systolic or greater than 120 mmHg diastolic, and were referred for immediate medical assessment. The program has been recently integrated into a more global vision for the prevention and control of cardiovascular disease in Calgary. Future plans include offering lipid assessments, assisting other communities to adopt the program and using the program to provide physical measures (of blood pressure, glucose, total and high density lipoprotein cholesterol, height and weight) to an ongoing questionnaire that surveys the health of Calgarians. The history of the program, its training methods, quality control, preliminary results and future plans are presented in detail to provide an example of a community-based program that could aid in the detection, monitoring and awareness of hypertension. PMID- 11773939 TI - An update: women, hypertension and therapeutic efficacy. AB - One in five Canadians has high blood pressure. The prevalence is as high as 58% in women between the ages of 65 and 74 years. Approximately 40% of stroke cases, 39% of myocardial infarction cases and 28% of end stage renal diseases are attributable to hypertension. Despite the burden that hypertension places on women, the effect of antihypertensive therapy on cardiovascular complications has not been well established. To address this knowledge gap, two meta-analyses with sex-specific results, including the most current randomized, controlled trials to evaluate hypertension treatment, were reviewed. The Individual Data Analysis of Antihypertensive (INDANA) intervention trials group and Quan and colleagues analyzed treatment benefits in 23,000 women and 19,975 men according to subgroup meta-analyses from 12 randomized, controlled trials that compared antihypertensive drug therapy with placebo. The meta-analyses demonstrated a statistically significant treatment benefit for all of the reported clinical outcomes in men of all ages and in black women. In women over the age of 54 years, antihypertensive treatment was associated with a significant reduction of fatal and nonfatal stroke, cardiovascular events and cardiovascular mortality. Overall, there was no significant difference in the relative treatment benefit in women and men; however, the absolute treatment benefit was lower in women than in men. Thus, the number needed to treat for the end points of fatal stroke, nonfatal stroke and cardiovascular events was one- to threefold higher for women than for men. Furthermore, white women between the ages of 30 and 54 years showed no treatment benefit or harm. Data from the 6.7-year follow-up in the Hypertension Detection and Follow-up Program (HDFP) trial suggested that this group of younger women might benefit from a longer duration of treatment. Indications for pharmacological intervention seem quite clear for all subgroups, excluding these younger women. Until further evidence is available for this low risk subgroup, the current recommendations for lifestyle modification cannot be challenged. PMID- 11773940 TI - Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder. AB - BACKGROUND: Several studies have shown that calcineurin may play a critical role in the signalling of cardiac hypertrophy in various experimental models. OBJECTIVE: To elucidate whether calcineurin is involved in cardiac hypertrophy due to energy metabolic disorder by using the juvenile visceral steatosis (JVS) mouse, which is a murine model of systemic carnitine deficiency. METHODS AND RESULTS: Cardiac hypertrophy in JVS mice (C3H strain) progresses gradually after birth and is present until eight weeks of age. In this study, calcineurin activity in JVS mice increased significantly at four weeks of age (the developing stage of cardiac hypertrophy) compared with age-matched control mice. Treatment with calcineurin inhibitor FK506 (0.5 or 1.0 mg/kg/day) from the age of four to eight weeks attenuated cardiac hypertrophy without beneficially affecting cardiac function. Gene expression, accompanied by cardiac hypertrophy, was also suppressed by the FK506 treatment. CONCLUSIONS: The activation of calcineurin is involved in the development of cardiac hypertrophy in the JVS mouse, and calcineurin inhibition may be useful for reducing cardiac hypertrophy. PMID- 11773941 TI - Right atrial mass. PMID- 11773943 TI - The 2001 Canadian Cardiovascular Society consensus guideline update for the management and prevention of heart failure. PMID- 11773945 TI - Oral pantoprazole for acid suppression in the treatment of patients with Zollinger-Ellison syndrome. AB - BACKGROUND: The management of patients with gastric acid hypersecretion due to gastrinoma, usually recognized as Zollinger-Ellison syndrome (ZES), was radically changed 10 years ago by the use of proton pump inhibitors. Surgical treatment now concentrates on tumour excision, and in the majority of patients, gastrectomy is no longer required to prevent complications of acid hypersecretion that can be managed pharmacologically. AIMS: To verify the ability of pantoprazole to control gastric acid hypersecretion and the clinical effects of acid hypersecretion in seven patients with documented ZES. METHODS: Pantoprazole was administered at an initial dose of 80 mg daily for seven days before basal acid output (BAO) was measured at 08:00, ie, 1 h before the next dose of pantoprazole was normally ingested. A lower (40 mg) or higher (120 mg or more) dose of pantoprazole was then used to keep the BAO in the therapeutic range (between 0.1 and 10 mmol/h) and to control clinical symptoms such as acid-related pain or diarrhea. RESULTS: BAO and clinical symptoms were controlled with pantoprazole 40 mg daily in one patient, 80 mg daily in two patients, 120 mg daily in three patients and 160 mg daily in one patient. CONCLUSIONS: Pantoprazole was able to control acid hypersecretion in ZES patients when administered in doses between 40 and 160 mg daily. An initial dose of 120 mg given before further titration of the drug regimen appears to be a reasonable therapeutic strategy. PMID- 11773946 TI - Clinical perspectives--biologics in IBD: What's all the fuss? AB - Up until the present time, agents with relatively nonspecific anti-inflammatory or immunomodulatory effects such as 5-acetylsalicylic acid, corticosteroids and azathioprine have been the mainstay of inflammatory bowel disease medical therapy. These drugs have been quite useful in one or more clinical settings, but they have been hampered by modest efficacy, significant toxicity or both. With greater understanding of the specific pathways of the gut mucosal immune response, it is hoped that newer biologic response modifiers will provide better efficacy, with an improved adverse event profile compared with older existing therapies. This article examines the evidence behind the use of biologic therapies such as anti-tumour necrosis factor-alpha, interleukin-10, interleukin 11, anti-integrin antibody and antisense intercellular adhesion molecule-1 oligonucleotide. PMID- 11773947 TI - Gastroparesis: prevalence, clinical significance and treatment. AB - The application of novel techniques to quantify gastric motor function and gastric emptying has yielded important insights into the prevalence, pathogenesis and clinical sequelae of gastroparesis. Both acute and chronic gastroparesis occur frequently; gastric emptying of solids is delayed in 30% to 50% of patients with diabetes mellitus, functional dyspepsia and gastroesophageal reflux disease. While many patients with gastroparesis experience upper gastrointestinal symptoms that adversely affect quality of life, the concept that symptoms are inevitably the direct outcome of delay in gastric emptying is now recognized to be overly simplistic. In contrast, the potential impact of gastroparesis on oral drug absorption and blood glucose control in patients with diabetes mellitus has probably been underestimated. While the use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy in symptomatic patients with gastroparesis, a number of novel pharmacological therapies are being evaluated, and preliminary studies using gastric pacing show promise. PMID- 11773948 TI - The use of probiotics in gastrointestinal disease. AB - Probiotics are living microorganisms that can affect the host in a beneficial manner. Prebiotics are nondigestible food ingredients that stimulate the growth and activity of probiotic bacteria already established in the colon. Efficacy of probiotic compounds has been shown in a wide range of gastrointestinal diseases. Lactobacillus GG alone, or the combination of Bifidobacterium bifidum and Streptococcus thermophilus, is effective in the treatment of Clostridium difficile, as well as in preventing the frequency and severity of infectious acute diarrhea in children. Prevention of antibiotic-induced diarrhea with the concomitant administration of either Lactobacillus GG or Saccharomyces boulardii has been demonstrated. The most successful studies involve the use of Lactobacillus GG at a dose of 1 x 1010 viable organisms per day and the yeast boulardii at a dose of 1 g/day. A probiotic preparation (VSL#3 - 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has shown promise in maintaining remission in ulcerative colitis and pouchitis, as well as in preventing the postoperative recurrence of Crohn's disease. The mechanism of action of probiotics may include receptor competition, effects on mucin secretion or probiotic immunomodulation of gut-associated lymphoid tissue. Oral administration of probiotic compounds has been demonstrated to be well tolerated and safe. However, while probiotics have the potential to improve human health and to prevent and treat some diseases, major improvements are needed in labelling and quality assurance procedures for probiotic compounds. In addition, well planned and controlled clinical studies are necessary to delineate fully the potential for probiotic compounds. PMID- 11773949 TI - ACE inhibitor-induced angioedema of the intestine: Case report, incidence, pathophysiology, diagnosis and management. AB - A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin converting enzyme (ACE) inhibitor-induced angioedema of the intestine (AIAI) occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound) is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy. PMID- 11773950 TI - Plexiform neurofibroma of the submandibular salivary gland in a child. AB - Plexiform neurofibromas in major salivary glands are rarely described. In the literature, most reported tumours have been present in the parotid gland region. A three-year-old boy with a family history of neurofibromatosis presented with a rapidly growing left submandibular mass. The clinical diagnosis was that of a neurofibroma rather than a primary salivary gland tumour. Resection of the lesion revealed a plexiform neurofibroma involving the submandibular gland. Although these tumours have a neurogenic rather than a salivary gland origin, they must be considered in the differential diagnosis of a salivary gland lesion in a patient with a history of neurofibromatosis. PMID- 11773951 TI - RE: Development of an assay for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for Crohn's disease. PMID- 11773953 TI - A new approach to the bending properties of hair fibers. AB - A new test developed to characterize the bending properties of treated or virgin hair fibers is described. The device consists of a pendulum that bends a sample made up of 39 parallel hair fibers at each swinging stroke. Hair bending stiffness can be assessed by the number of strokes observed until the pendulum stops. The mechanical behavior of natural hair fibers is related to their geometric characteristics. The effects of various hair treatments can be assessed by this method. PMID- 11773954 TI - A modified cup scrub method for assessing the antibacterial substantivity of personal cleansing products. AB - An improved in vivo method for evaluating the antibacterial substantivity or residual effectiveness of bar soaps and other personal cleansing products is presented. The effectiveness of an antibacterial bar soap containing 1.5% 3, 4, 4'-trichlorocarbanilide (TCC) versus its soap vehicle was evaluated under simulated conditions considered optimal for bacterial growth, proliferation, and possible infection. A washout period to clear the skin of any antimicrobial agents previously used was followed by a treatment period in which the subjects washed one of their forearms with the antibacterial soap and the other forearm with the soap vehicle. Either immediately or 24 hours following the final wash, three test sites on both forearms were inoculated with S. aureus and occluded with Hill Top Chamber patches. At intervals of 30 minutes, two hours and five hours, the patches were removed. The bacteria on the skin were harvested using the Williamson-Kligman scrub technique (1,2) to determine the number of surviving CFUs at each time period. The method successfully demonstrated that sufficient TCC had remained on the skin for 24 hours after the final wash to effectively inhibit the growth of S. aureuso on the skin for as long as five hours after inoculation. PMID- 11773955 TI - Hair photoprotection by dyes. AB - We have found that hair dyes protect hair against photodamage. The efficacy of photoprotection of dye products has been measured by monitoring the tensile strength of hair fibers and the integrity of the disulfide bonds in the fibers. Although the hair dyed with permanent dye products are initially weakened due to oxidative chemical damage, they also show a slower rate of degradation upon photoirradiation, compared to the undyed hair. Thus, a less appreciated benefit of using hair colors is their ability to provide protection against sun damage. PMID- 11773956 TI - Diurnal variation affects age-related profile in skin thickness. AB - We have previously demonstrated that over the course of each day there are changes in skin thickness that can be measured by B-mode ultrasonography. This suggests that there is a shift in dermal fluid from the face toward the legs by gravity, resulting in a diurnal variation in skin thickness. Therefore, age dependent profiles in skin thickness were evaluated by B-mode ultrasonography in the morning or in the afternoon for 130 normal Japanese females aged 18-83 years. Three areas of the face (the forehead, the corners of the eye, and the cheeks) were measured as distinctively sun-exposed areas while the flexion side of the forearm was measured as a weakly sun-exposed area. A weak correlation between skin thickness and age was found in all areas measured (positive for the forehead, the corners of the eye, and the cheeks; negative for forearms) in the morning but not in the afternoon, when only a weak positive correlation was observed in the cheek. These results indicate that when measuring skin thickness, an appropriate time for taking measurements should be selected with consideration of the movements of dermal fluid over the course of each day. PMID- 11773957 TI - Simultaneous quantitative determination of fluorine and sodium monofluorophosphate in oral hygiene products. AB - An ion chromatographic method for simultaneous quantitative determination of fluorine and sodium monofluorophosphate in oral hygiene products is described. The liquid chromatographic system consisted of an IC A1 polymethacrylate-based anion exchanger and carbonate buffer (pH 9.85) as the mobile phase with a conductive detector. Various excipient ions were investigated with respect to their interference with the determination of fluoride. Comparison with results obtained from a fluoride-ion electrode technique show good agreement. PMID- 11773962 TI - The origins of mouse genetics: beyond the Bussey Institution.II. Defining the problem of mouse supply: the 1928 National Research Council Committee on Experimental Plants and Animals. PMID- 11773964 TI - Characterization of a putative murine mitochondrial transporter homology of hMRS3/4. AB - We report here a novel murine gene, Mrs3/4, encoding a putative mitochondrial transporter homologous to the yeast mitochondrial RNA splicing protein 3 and 4 (yMRS3&4) and its human counterpart hMRS3/4. By analyses of radiation hybrids, Mrs3/4 was mapped to mouse Chromosome (Chr) 19 between D19Mit66 and D19Mit24 with a distance of 22.4 cR to D19Mit66, a region that is syntenic to human Chromosome 10q24, where the human gene is located. Structural analysis shows that these proteins belong to the mitochondrial carrier family (MCF), which is characterized by three repeats with two transmembrane domains in each repeat. The murine Mrs3/4 gene has two splicing forms similar to the human homolog. The long form corresponds to the 341-amino acid (aa) protein with six transmembrane domains, and the short form corresponds to the 177-aa protein with three transmembrane domains. Both forms have well-conserved signature sequences of MCF. Targeting experiments showed that both forms have mitochondrial localization. Northern blot analyses showed that Mrs3/4 is ubiquitously expressed as a 1.8-kb transcript with a relative abundance in the heart, liver, kidney, and testis. In conclusion, the reported Mrs3/4 gene shows a strong conservation, mitochondrial protein localization, and a ubiquitous expression, which suggests that it has an important role in mammalian cells, most likely as an ion transporter across the mitochondrial inner membrane. PMID- 11773965 TI - Inheritance patterns of maternal alleles in imprinted regions of the mouse genome at different stages of development. AB - Deviations from Mendelian 1:1 transmission ratio have been observed in mice and humans. With few exceptions, the mechanism leading to transmission-ratio distortion (TRD) remains obscure. We proposed that a genomic imprinting mechanism plays a key role in the genesis of grandparental origin-dependent TRD (Naumova et al. 2001). To further test this hypothesis, we analyzed the transmission of grandparental alleles at three imprinted regions of the mouse genome known to contain genes required for embryo development. We found and replicated moderate (58%: 42%) TRD in favor of grandmaternal alleles in the imprinted region of maternal distal Chromosome (Chr) 12 among female offspring. Comparison of transmission ratios at the distorted region of Chr 12 among 3-week-old mice with those in embryos suggests that the distortion in favor of grandmaternal alleles is owing to postimplantation embryo loss. The absence of grandparental origin dependent TRD for maternal Chr 6 and 7 implies that the relationship between TRD and imprinting is complex. Most likely, multiple conditions are required for TRD to occur. PMID- 11773963 TI - Genetic, physical, and comparative map of the subtelomeric region of mouse Chromosome 4. AB - The subtelomeric region of mouse chromosome (Chr) 4 harbors loci with effects on behavior, development, and disease susceptibility. Regions near the telomeres are more difficult to map and characterize than other areas because of the unique features of subtelomeric DNA. As a result of these problems, the available mapping information for this part of mouse Chr 4 was insufficient to pursue candidate gene evaluation. Therefore, we sought to characterize the area in greater detail by creating a comprehensive genetic, physical, and comparative map. We constructed a genetic map that contained 30 markers and covered 13.3 cM; then we created a 1.2-Mb sequence-ready BAC contig, representing a 5.1-cM area, and sequenced a 246-kb mouse BAC from this contig. The resulting sequence, as well as approximately 40 kb of previously deposited genomic sequence, yielded a total of 284 kb of sequence, which contained over 20 putative genes. These putative genes were confirmed by matching ESTs or cDNA in the public databases to the genomic sequence and/or by direct sequencing of cDNA. Comparative genome sequence analysis demonstrated conserved synteny between the mouse and the human genomes (1p36.3). DNA from two strains of mice (C57BL/6ByJ and 129P3/J) was sequenced to detect single nucleotide polymorphisms (SNPs). The frequency of SNPs in this region was more than threefold higher than the genome-wide average for comparable mouse strains (129/Sv and C57BL/6J). The resulting SNP map, in conjunction with the sequence annotation and with physical and genetic maps, provides a detailed description of this gene-rich region. These data will facilitate genetic and comparative mapping studies and identification of a large number of novel candidate genes for the trait loci mapped to this region. PMID- 11773966 TI - A mouse model of Waardenburg syndrome type 4 with a new spontaneous mutation of the endothelin-B receptor gene. AB - Waardenburg syndrome (WS) is a hereditary auditory-pigmentary syndrome with hearing impairment and pigmentation anomaly of the skin and iris. In addition to these major symptoms, WS type 4 is associated with Hirschsprung disease. To date, three genes responsible for WS4 have been cloned: genes for a transcription factor SOX10, endothelin 3 (EDN3), and endothelin B receptor (EDNRB). We here describe a novel mutant mouse with a mutation of the Ednrb gene, and propose the mouse as an animal model of WS4. These mutants are with mixed genetic background of BALB/c and MSM (an inbred strain of Japanese wild mice) and have extensive white spotting. They died between 2 and 7 weeks after birth owing to megacolon: their colon distal to the megacolon lacked Auerbach's plexus cells. Interestingly, these mutants did not respond to sound, and the stria vascularis of their cochlea lacked intermediate cells, i.e., neural crest-derived melanocytes. Since these symptoms resembled those of human WS4 and were transmitted in autosomal recessive hereditary manner, the mutants were named WS4 mice. Breeding analysis revealed that WS4 mice are allelic with piebald-lethal and JF1 mice, which are also mutated in the Ednrb gene. Mutation analysis revealed that their Ednrb lacked 318 nucleotides encoding Ednrb transmembrane domains owing to deletion of exons 2 and 3. Interaction between endothelin 3 and its receptor is required for normal differentiation and development of melanocytes and Auerbach's plexus cells. We concluded that a missing interaction here led to a lack of these cells, which caused pigmentation anomaly, deafness, and megacolon in WS4 mice. PMID- 11773967 TI - Insertional mutation of the Attractin gene in the black tremor hamster. AB - The hamster black tremor (bt) mutation induces a black coat color and a defective myelination in the central nervous system (CNS) that manifests as a tremor. On the other hand, loss-of-function mutations of the Attractin (Atrn) gene, such as Atrnmg, Atrnmg-L, and Atrnmg-3J in mice, and Atrnzi in rats, induce both darkening of coat color and hypomyelination and vacuolation in the CNS. The close resemblance of the mutant phenotypes led us to postulate that the bt/bt hamster also might harbor a mutation in Atrn. Here, we cloned the hamster Atrn cDNA and identified bt as a loss-of-function mutation of Atrn. While the human and rat Atrn genes encode both membrane- and secreted-type proteins, the hamster Atrn gene encoded only membrane-type protein with 1,427 amino acids, as in the case of the mouse. Hamster Attractin protein had 93.6%, 96.8%, and 96.8% identities with human, rat, and mouse membrane-type Attractin. In the brain of the bt/bt hamster, aberrant transcripts with more than three size species were observed, and the most predominant transcript encoded the truncated Attractin without transmembrane domain. In the Atrn gene of bt/bt hamster, an approximately 10-kb DNA fragment, which had 557-bp direct repeats in both ends and was flanked by the identical 6 bp target duplication sequences, was inserted into exon 24. In addition, the insertion was cosegregated with neurodegeneration in the CNS of 50 intercross progeny. These results indicated that the hamster bt mutation was the approximately 10-kb retrotransposon-like insertion into the Atrn gene, which resulted in aberrant transcripts. The bt/bt hamster will provide a useful tool for further understanding of the pleiotropic functions of Attractin. PMID- 11773968 TI - Multiple blood pressure QTL on rat Chromosome 2 defined by congenic Dahl rats. AB - Linkage analysis previously demonstrated a blood pressure quantitative trait locus (QTL) on rat Chromosome 2 (Chr 2) in crosses utilizing Dahl salt-sensitive (S) rats. The present work dissects this QTL by using congenic strains in which segments of Chr 2 from Wistar Kyoto rats (WKY) are placed on the S genetic background. Two distinct QTLs were found where one QTL was anticipated. These each accounted for a blood pressure of 15-20 mm Hg in rats fed 2% NaCl diet for 24 days. One QTL was in the <9-cM interval between D2Rat35 and D2Wox18 (Fgg), and the other was in the <7-cM interval between D2Wox18 (Fgg) and D2Mgh10. A third tentative QTL was suggested, but not clearly established, in the <3-cM interval between D2Mgh10 and D2Rat259. PMID- 11773969 TI - Mapping of an immotile short tail sperm defect in the Finnish Yorkshire on porcine Chromosome 16. AB - An immotile short tail sperm defect has recently been identified as a hereditary disorder present within the Finnish Yorkshire pig population. The syndrome is inherited as an autosomal recessive disease exclusively expressed in male individuals as shorter sperm tail length and immotile spermatozoa. Based on the assumption of a recent common origin of the disease-causing mutation, a genome wide search was performed with 228 evenly spaced microsatellites by homozygosity mapping of affected and unaffected DNA pools. One locus, SW2411 on Chr 16, demonstrated a significantly skewed allele distribution between the two pools. Linkage analysis of five markers in this region mapped the disease-causing gene within a 6-cM confidence interval region with a highest LOD score of 7.7 at marker SW419. It appears that three-marker haplotypes can be used for marker assisted selection within analyzed pedigrees. Furthermore, future fine mapping may reveal a more precise population-wide associated haplotype and facilitate identification of a new gene affecting sperm tail development. PMID- 11773970 TI - CAN--a pan-carnivore SINE family. AB - Short retroposons or short interspersed elements (SINEs) constituting 5-10% genome have been isolated from various organisms. CAN SINEs initially found in American mink were named after dogs (Canis), and the range of their distribution in the genomes of carnivores and mammals in general remained topical. Here we demonstrate CAN sequences in representatives of all carnivore families, but not beyond carnivores, on the basis of sequence bank search and genomic PCR. Analysis of their distribution supports division of carnivores into caniform (dogs, mustelids, raccoons, bears, and pinnipeds) and feliform (cats, civets, and hyenas) lineages. CAN structure is considered in the context of their function and evolution. PMID- 11773971 TI - High-resolution mapping of the Gli3 mutation extra-toes reveals a 51.5-kb deletion. PMID- 11773972 TI - Human O-GlcNAc transferase (OGT): genomic structure, analysis of splice variants, fine mapping in Xq13.1. PMID- 11773973 TI - Reversion of the malignant phenotype of gastric cancer cell SGC7901 by c-erbB-2 specific hammerhead ribozyme. AB - The c-erbB-2/neu-encoded protein p185 is closely related to the growth and metastasis of adenocarcinoma. We sought to reverse the malignant phenotype of gastric cancer cell line SGC7901 with c-erbB-2-specific ribozyme. We designed the ribozyme and generated the in vitro transcription vectors of the ribozyme and its substrate. In vitro cleavage reaction indicated that the ribozyme catalyzed 79.3% target RNA in 1 hour at 37 degrees C. Then, we generated the eucaryotic expression vectors of the ribozyme and transfected them into SGC7901 cells, which highly express p185. Analyses showed that the c-erbB-2 mRNA and p185 were reduced remarkably in the ribozyme-transfected cells. The growth rate of the ribozyme transfected cells was much lower than that of the control group. Tumorigenicity was also decreased dramatically in nude mice. The results demonstrated that c erbB-2-specific ribozyme may inhibit the malignancy of gastric cancer cells SGC7901. PMID- 11773974 TI - Local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma. AB - Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with "bystander effects" after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome. PMID- 11773975 TI - Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes. AB - A critical issue for cancer treatment is control of metastatic or disseminated tumors. Although immune gene therapy has been considered as a possible strategy for treatment of such tumors, successful results have not yet been obtained. To evoke antitumor immunity more efficiently, macrophage inflammatory protein-1beta (MIP-1beta) was used for gene therapy of colon cancer in mice. Injection of hemagglutinating virus of Japan (HVJ) cationic liposomes-MIP-1beta into subcutaneous tumor masses resulted in local expression of MIP-1beta and local accumulation of CD4(+) T lymphocytes. Few studies of cancer gene therapies have targeted peritoneal dissemination. In a mouse model of peritoneal dissemination of colon tumor, we used a luciferase-based assay to demonstrate that HVJ cationic liposomes had high tumor specificity and were effective vectors for transfer of genes in peritoneal dissemination. When mice were treated by intraperitoneal injection of HVJ cationic liposomes containing the MIP-1beta gene, the survival periods of the MIP-1beta-treated mice were significantly longer than those of control mice. Therefore, this HVJ cationic liposome strategy may serve as a powerful tool against peritoneal disseminated cancer. PMID- 11773976 TI - Gene transfer of interleukin 13 receptor alpha2 chain dramatically enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in human prostate cancer xenografts. AB - IL-13Ralpha2 chain, the primary interleukin-13 (IL-13) binding protein, plays an important role in IL-13 binding and internalization. Based on these findings, in our previous study we transiently transfected four cancer cell lines that do not express IL-13Ralpha2 chain and demonstrated that these cells acquired increased sensitivity to IL-13 receptor-targeted recombinant cytotoxin, IL13-PE38QQR, which is composed of IL-13 and a mutated form of a Pseudomonas exotoxin. Although some prostate cancer cell lines express functional IL-13R, they are not highly sensitive to IL-13 cytotoxin. Here we investigated whether human prostate cancer and normal prostate epithelial cell lines express IL-13Ralpha2 chain and whether they can be sensitized to the cytotoxic effect of IL-13 cytotoxin after transient or stable gene transfer of IL-13Ralpha2 chain. Gene transfer of IL-13Ralpha2 chain improved binding activity of IL-13 and sensitivity to IL-13 cytotoxin in vitro. In vivo experiments demonstrated that gene transfer of IL-13Ralpha2 chain dramatically enhanced the antitumor activity of IL-13 cytotoxin in human prostate cancer xenograft models. These results suggest that IL-13R-targeted cytotoxin therapy of prostate cancer may be dramatically enhanced by gene transfer of IL 13Ralpha2 chain and this strategy, the combination of gene therapy and cytotoxin therapy, may be utilized in the treatment of localized prostate cancer. PMID- 11773977 TI - Adenoviral delivery of TIMP1 or TIMP2 can modify the invasive behavior of pancreatic cancer and can have a significant antitumor effect in vivo. AB - Pancreatic carcinomas overexpress several matrix metalloproteinases (MMPs), in particular MMP2 and MMP9. These enzymes are involved in the degradation of the extracellular matrix to aid tumor cell invasion. The aim of this study was to investigate the effect of TIMP gene therapy on human pancreatic cancer. Human TIMP1 or TIMP2 has been introduced in pancreatic tumor cells under the control of a constitutive promoter using adenoviral vectors, and the effect on tumor invasion observed. It has been demonstrated in vitro that the TIMP-expressing pancreatic tumor cells were significantly less invasive than those cells transfected with a control vector. In vivo, adenoviral delivery of TIMP1 or TIMP2 to nude mice harboring intraperitoneal human pancreatic cancers resulted in prolonged survival compared with control mice if the gene therapy was given early (P<.009 and P<.0293, respectively). The in vivo experiments demonstrated evidence of gene transfer by adenoviral vectors to tumor cells and murine mesenteric cells. There was no evidence of transgene expression in distant organs. These experiments have proved the hypothesis that TIMP overexpression in pancreatic cancer cells can modify the invasive phenotype. Also, TIMP gene transfer to human tumor cells is possible both in vitro and in vivo. PMID- 11773978 TI - Development of lentiviral vectors for antiangiogenic gene delivery. AB - Growth and metastasis of malignant tumors requires angiogenesis. Inhibition of tumor-induced angiogenesis may represent an effective cytostatic strategy. We have constructed recombinant self-inactivating lentiviral vectors expressing angiostatin and endostatin, and have tested their antiangiogenic activities. As VSV-G-pseudotyped lentiviral vectors showed low relative transduction titers on bovine aortic and human umbilical vein endothelial cells, it was difficult to achieve significant inhibition of endothelial cell growth by lentivirus-mediated antiangiogenic gene transfer directly to endothelial cells without concomitant vector-associated cytotoxicity. However, lentivirus vectors could efficiently and stably transduce T24 human bladder cancer cells that are relatively resistant to adenovirus infection due to loss of coxsackievirus-adenovirus receptor expression. Long-term expression and secretion of angiostatin and endostatin from lentivirus-transduced T24 cells resulted in significant inhibition of cellular proliferation on coculture with endothelial cells. This report represents the first use of lentivirus-based vectors to deliver the antiangiogenic factors, angiostatin and endostatin, and suggests the potential utility of antiangiogenic gene therapy with lentiviral vectors for the treatment of cancer. PMID- 11773979 TI - A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir. AB - The c-erbB-2 gene is frequently overexpressed in human breast cancers as a result of gene amplification and/or elevated transcription. We therefore examined a possible usage of promoter regions of the c-erbB-2 gene to express a suicide gene preferentially in breast cancer cells. Previous studies did not reveal the minimal promoter region that enabled transcriptional activation specific to breast cancer cells. The present reporter gene assays using deletion mutants of the c-erbB-2 promoter region demonstrated that the 251-bp (-213/+38 from the transcriptional start site), but not the 125-bp, fragment (-87/+38) could direct transcription of the linked luciferase gene better than the SV40 immediate early promoter in breast cancer cells. In contrast, the 251-bp fragment-mediated promoter activity in nonbreast cancer cells and in normal fibroblasts was lower than the activity by the SV40 promoter. The 126-bp fragment (-213/-87) thereby contains a cis-acting element(s), which is responsible for the preferential transcriptional activity in breast cancer cells. An electrophoretic mobility shift assay suggested that a possible modification of a transcriptional factor was involved in the tumor specificity. Transfection with the plasmid DNA containing the herpes simplex virus thymidine kinase gene linked with the 251-bp promoter (p256-TK) resulted in increased sensitivity to ganciclovir in breast cancer, but not in nonbreast cancer cells. Administration of ganciclovir into nude mice bearing human breast tumors that were transfected with the p256-TK DNA suppressed subsequent growth of the transplanted tumors. These results suggest that delivery of a suicide gene linked with the 251-bp c-erbB-2 promoter can be a feasible therapeutic strategy specific to breast cancer. PMID- 11773980 TI - Simultaneous inhibition of Rac1 and IKK pathways sensitizes lung cancer cells to TNFalpha-mediated apoptosis. AB - Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumor necrosis factor alpha (TNFalpha) has been shown to regulate both apoptotic and antiapoptotic pathways. Activation of the transcription factor NF-kappaB appears to be the critical determinant of the antiapoptotic response to TNFalpha exposure in epithelial cells. A549 human lung carcinoma cells were infected with adenoviral constructs carrying dominant negative mutants of Rac1 and IKK or constitutively active mutant of Rac1, upstream effectors in TNF-mediated NF kappaB activation. Cell death, apoptosis, and NF-kappaB activation were subsequently measured in response to TNFalpha exposure. Although TNFalpha alone had no cytotoxic effect, the expression of the dominant negative mutant of IKKbeta (Ad.IKKbetaKA) resulted in apoptotic cell death following TNFalpha exposure. Similarly, dominant negative mutant to Rac1 (Ad.N17Rac1) further sensitized A549 cells to IKKbetaKA-mediated TNFalpha-induced cell death. Conversely, a dominant active form of Rac1 (Ad.V12Rac1) ameliorated the cell death response to concurrent IKKbeta dominant negative mutant infection and TNFalpha exposure. These results suggest that concurrent inhibition of Rac1 and IKK pathways sensitizes lung cancer cells to TNFalpha-induced apoptosis. PMID- 11773981 TI - An overview of the Tenth International Conference on Cancer Gene Therapy. AB - Dr. Scanlon, the new president (2001-2002) of the International Society of Cancer Gene Therapy, gave the conference summary and an overview of gene therapy in the new millennium. The conference reflected the progress made in the development of new promoters and improved delivery systems for gene therapy. Many presentations and posters focused on the progress in these areas. These scientific findings in the field of gene therapy may ultimately be exploited in the future developments of stem cell research. Conversely, challenges still remain before gene therapy will significantly impact cancer. The basic science of the cancer model systems lacked the ability to reflect the clinical reality of patient treatment. This places the burden on the physicians to be more vigilant to subtle changes in patient response that were not observed in the preclinical models. The bystander effect has yet to be fully understood and needs further clinical validation. Systemic delivery needs to be further addressed before a marketable product can be developed. The delivery systems discussed at the conference lack the ability to achieve pharmacological doses of therapeutic genes in the target tissue. Until these challenges are addressed, gene therapy will remain on the sidelines as a cancer modality. Yet, the field should be optimistic with the current progress. The future influences of the digital and genomic revolution in the health care industry will certainly impact the design of products for gene therapy. Dr. Scanlon concluded that the education of scientists would cross over into diverse disciplines so that novel observations will be exploited for new therapies. This gene therapy series will continue with the International Conference on the Gene Therapy of Cancer, scheduled for December 13-15, 2001, in San Diego, CA. PMID- 11773983 TI - What should be the goal blood pressure? PMID- 11773984 TI - ACE inhibitors in vascular disease: some PROGRESS, more HOPE. PMID- 11773985 TI - The protective effect of blocking angiotensin in both type I and type II diabetics with nephropathy. PMID- 11773986 TI - Blood pressure levels, risk factors and antihypertensive treatments: lessons from the SHEAF study. AB - OBJECTIVES: The SHEAF study (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-up) is a 3-year prospective cohort study of French elderly (> or =60 years) hypertensive patients designed to assess whether home blood pressure (HBP) measurement provides additional prognostic information over office blood pressure (OBP) in terms of cardiovascular mortality and morbidity. The objective of the present work is to describe the baseline data of the population enrolled in the SHEAF study with special emphasis on blood pressure control in treated hypertensives. METHODS: During the 2-week initial inclusion phase, baseline demographics, cardiovascular risk factors, antihypertensive treatments as well as office and home blood pressure were recorded. Baseline OBP was assessed using a mercury sphygmomanometer (three consecutive measurements during two visits performed 2 weeks apart). HBP was performed over a 4-day period (three consecutive measurements in the morning and in the evening). RESULTS: A total of 4939 (95%) of the 5211 patients included in the SHEAF study were treated with at least one antihypertensive drug. Their ages ranged from 60 to 99 years (mean age 70 +/- 7 years); 49% were men, 12% had a previous history of coronary artery disease, 14% diabetes and 43% a treated dyslipidaemia. A total of 45% of the treated patients received a single antihypertensive drug, 34% two drugs, 21% three drugs or more. Overall 23% of treated hypertensives were normalised at the doctor's office (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) and 27% at home (home systolic BP <135 mm Hg and home diastolic BP <85 mm Hg). Poor blood pressure control was associated with age, an increasing presence of diabetes and prescription of several antihypertensives. The proportion of subjects with controlled blood pressure decrease with age from 26% (60-69 years) to 21% (> or =80 years). Blood pressure control of diabetic patients was particularly poor as only 19% had an OBP <140/90 mm Hg and 6% a blood pressure <130/85 mm Hg. The percentage of patients with controlled OBP decreased from 26% when receiving a single antihypertensive drug to 11% when receiving four antihypertensives or more. CONCLUSION: In the SHEAF study, less than one-third of the patients had an OBP adequately controlled thus confirming previous studies performed in younger populations. Presence of associated cardiovascular risk factors including diabetes did not give rise to a better blood pressure control. When blood pressure control was assessed using HBP measurement similar results were found. As the beneficial effect of antihypertensive treatment has been particularly well established in the elderly, the data of this study underlines the need for a closer and more rigorous management of elderly hypertensives. PMID- 11773987 TI - Effect of two antihypertensive combinations on metabolic control in type-2 diabetic hypertensive patients with albuminuria: a randomised, double-blind study. AB - The objective of this study was to compare, at equal blood pressure (BP) reduction, the effect of two different combinations on metabolic control and albuminuria in type 2 diabetic hypertensive patients with albuminuria. This was a prospective, randomised, double-blind, parallel, controlled trial carried out in 11 Spanish hospitals. A total of 103 type 2 diabetic patients with stable albuminuria and BP not controlled on monotherapy were randomised of which 93 finished the study. After a 4-week single-blind placebo period, patients were randomised to verapamil SR/trandolapril 180/2 mg (VT) or to enalapril/hydroclorothiazide 20/12.5 mg (EH). Treatment duration was 6 months. The main outcome measures were changes in BP, 24-h albuminuria, blood glucose and glycated haemoglobin. Overall BP was significantly reduced from 157.3 +/- 12.0/98.3 +/- 6.4 mm Hg to 140.5 +/- 14.5/86.1 +/- 8.2 mm Hg (P < 0.001) and albuminuria significantly decreased from 508.6 +/- 693.8 mg/24 h to 253.4 +/- 517.2 mg/24 h (P < 0.001), both without significant differences between treatments. Glycated haemoglobin was not modified on VT: baseline, 5.91 +/- 1.43%; end of treatment, 5.94 +/- 1.62%, but increased on EH: baseline, 5.96 +/- 1.25%; final, 6.41 +/- 1.51%, (ANOVA interaction P = 0.040). At the end of the study, a blood glucose <126 mg/dL was attained in 72.7% of the VT group-improving in 29.5% and worsening in 6.8% of patients (P = 0.021)-and in 50% of the EH group, 13.6% of patients improved and 11.4% worsened (P = 1.000). There were no changes in body weight, serum creatinine, uric acid, potassium, cholesterol, tryglicerides and serum albumin. In hypertensive type 2 diabetic patients not controlled on monotherapy, both treatments similarly reduced albuminuria. The combination verapamil/ trandolapril seems to allow a better metabolic control than enalapril/hydroclorothiazide. PMID- 11773988 TI - Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension. AB - The objective of this study was to compare quality of life and incidence of dry persistent cough among patients treated with eprosartan and enalapril for mild moderate hypertension. This was a randomised 26-week double-blind controlled trial carried out in clinics in nine countries of North America, Europe and South Africa. A total of 529 patients aged 18 and over with diastolic blood pressure between 95 mm Hg and 114 mm Hg were studied. Treatment comprised of eprosartan or enalapril monotherapy for 12 weeks with the option of hydrochlorothiazide addition for the remaining 14 weeks. The primary outcome measures were cough and the Psychological General Wellbeing Index (PGWB) total and subscales (anxiety, self-control, depression, general health, positive wellbeing and vitality). The results were that 17.8% of enalapril patients and 13.2% of eprosartan patients withdrew from randomised treatment. Those on enalapril were twice as likely to have gained a definite or possible cough by study end point as those on eprosartan (7.6% vs 3.2%) P = 0.099. At monotherapy end point the differences were greater (9.9% vs 2.1%) and of statistical significance, P = 0.001. Patients treated with enalapril, however, had small but significant improvements in measures of self-control and total PGWB compared with those on eprosartan. The effect sizes of 0.2 or less indicated that there were small differences. In conclusion eprosartan was associated with fewer coughs than enalapril but it performed less well on some aspects of quality of life. PMID- 11773989 TI - Quality of life and cough on antihypertensive treatment: a randomised trial of eprosartan, enalapril and placebo. AB - The objective of this study was to compare the quality of life and incidence of dry cough with the angiotensin II antagonist eprosartan, the ACE-inhibitor enalapril, and placebo, in hypertensive patients with a history of ACE-inhibitor cough. The study was a multicentre, randomised, double-blind, parallel group controlled trial. A total of 136 patients judged to have ACE-inhibitor cough during single-blind enalapril treatment which was lost during a subsequent placebo washout phase, were randomised to receive either eprosartan 300 mg twice daily, or enalapril 20 mg once daily, or placebo for 6 weeks. Self-completion questionnaires assessing quality of life and cough were examined at baseline and end of study. At study end point 23% of patients in the enalapril group and 5% in the eprosartan and placebo groups reported cough (which included definite, probable and possible coughs) (P = 0.02). After adjusting for multiple comparisons, the eprosartan group was not significantly different from either placebo or enalapril. There were no significant differences in the Psychological General Wellbeing Index (PGWB). In conclusion the incidence of self-reported cough on eprosartan was similar to that on placebo, and lower than on enalapril but this difference was not significant when adjustments were made for multiple comparisons. There were no differences in quality of life. PMID- 11773990 TI - Blood pressure and its reactivity in the offspring of first cousin hypertensive and first cousin normotensive parents: a preliminary report. AB - The aim of this preliminary study was to determine whether young offspring of first cousin hypertensive parent(s), have higher blood pressure (BP) reactivity in response to their first BP measurement, as compared to the offspring of first cousin normotensive parents. The BP of 135 boys aged 9-10 years was measured, for the first time ever, after a 10-min supine rest, and subsequently, twice at 10 min intervals. The offspring of first cousin hypertensive parent(s) reacted with significantly higher systolic and diastolic BP than the offspring of normotensive first cousin parents in all three measurements. This study indicates that at an early age, the offspring of first cousin hypertensive parents, react with exaggerated BP response at their first casual BP measurement. We hypothesise that familial aggregation of BP may show more expression amongst the offspring of consanguineous marriage of hypertensive parent(s). PMID- 11773991 TI - ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients. AB - The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation. PMID- 11773993 TI - Annual Scientific Meeting of the British Hypertension Society. 10-12 September 2001, Oxford, UK. Abstracts. PMID- 11773992 TI - Night time blood pressure and cardiovascular structure in a middle-aged general population in northern Italy: the Vobarno Study. AB - The aim was to determine, in a cross-sectional study, the relation between structural alterations in the heart and carotid arteries, and blood pressure (BP) changes from day to night time, measured by ambulatory BP (ABP). In 225 untreated subjects (107 F, 118 M, age range 48-64 years) and 59 treated subjects (24 M, 35 F, age range 50-64), living in a small town of northern Italy (Vobarno, Brescia) carotid intima media thickness as well as the occurrence of plaque, were evaluated by ultrasound. Echocardiographic left ventricular (LV) mass was measured according to the Penn Convention. BP was determined by clinic measurement and by 24-h non-invasive ABP monitoring. Subjects were divided in two groups, according to the decrease of night time systolic BP (SBP) "dippers" (SBP decreased by at least 10% during night time) and "non-dippers" (decrease of night time SBP <10%). The intima-media thickness in the common carotid, in the carotid bifurcation, in the internal carotid artery and average intima-media thickness were significantly greater in untreated non-dippers as compared with dipper subjects (ANOVA P < 0.05). A significantly higher prevalence of plaque was observed in untreated non-dippers as compared with dippers (P = 0.002). After adjusting for age, sex, 24-h SBP, and smoking, IMT in the carotid bifurcation and average intima-media thickness remained significantly greater in non-dipper subjects (P < 0.05 for all comparisons). No significant differences in LV mass were observed between dippers and non-dipper subjects. In conclusion, in a general population of unselected middle-aged subjects, night time BP values, among other risk factors, seem to represent an important determinant of carotid wall structure. PMID- 11773998 TI - Mechanisms of biofilm formation in paper machine by Bacillus species: the role of Deinococcus geothermalis. AB - Mechanisms for the undesired persistence of Bacillus species in paper machine slimes were investigated. Biofilm formation was measured for industrial Bacillus isolates under paper machine wet-end-simulating conditions (white water, pH 7, agitated at 45 degrees C for 1-2 days). None of the 40 tested strains of seven Bacillus species formed biofilm on polished stainless steel or on polystyrene surfaces as a monoculture. Under the same conditions, Deinococcus geothermalis E50051 covered all test surfaces as a patchy thick biofilm. The paper machine bacilli, however, formed mixed biofilms with D. geothermalis E50051 as revealed by confocal microscopy. Biofilm interactions between the bacilli and the deinococci varied from synergism to antagonism. Synergism in biofilm formation of D. geothermalis E50051 was strongest with Bacillus coagulans D50192, and with the type strains of B. coagulans, B. amyloliquefaciens or B. pumilus. Two B. licheniformis, one B. amyloliquefaciens, one B. pumilus and four B. cereus strains antagonized biofilm production by D. geothermalis. B. licheniformis D50141 and the type strain of B. licheniformis were the strongest antagonists. These bacteria inhibited deinococcal growth by emitting heat-stable, methanol soluble metabolite(s). We conclude that the persistence of Bacillus species in paper machine slimes relates to their ability to conquer biofilms formed by primary colonizers, such as D. geothermalis. PMID- 11773997 TI - Survival, root colonisation and biocontrol capacities of Pseudomonas fluorescens F113 LacZY in dry alginate microbeads. AB - Cells of Pseudomonas fluorescens F113 LacZY were encapsulated in alginate and their survival and ability to colonise sugar beet were evaluated. To assess survival, the formulation, composed of dry alginate microbeads of 300- to 700 microm diameter, was stored 1 year at 28+/-2 and 4+/-2 degrees C and then tested against pathogenic fungi Pythium ultimum and Rhizoctonia solani in in vitro inhibition experiments. The same material was also used as inoculant for protection of sugar beet against Py. ultimum in microcosm experiments. The results obtained indicated that, although drying alginate beads resulted in a significant reduction of bacterial viability, the use of microbeads enabled a satisfactory level of root colonisation and protection, at least under microcosm conditions. The capability of the encapsulated cells to produce the antifungal metabolite 2,4-diacetylphloroglucinol (Phl) was not significantly affected by 12 months storage. PMID- 11773999 TI - Molecular genetics and industrial microbiology--30 years of marriage. AB - Thirty years ago, molecular genetics and industrial microbiology joined their hands in marriage. The event took place in Prague at the first Symposium on the Genetics of Industrial Microorganisms. My closing plenary lecture, titled "The Marriage of Genetics and Industrial Microbiology--After a long Engagement, a Bright Future," dealt with industrial uses of mutants, the lack of success with genetic recombination, control of branched and unbranched pathways and thoughts about the future, e.g., identifying the biochemical sites of beneficial mutations, exploitation of recombination and genetic means to increase production of enzymes. It is quite amazing that the Symposium was held 3 years before the advent of recombinant DNA technology. This important meeting was followed in 1976 by the first Genetics and Molecular Biology of Industrial Microorganisms (GMBIM) meeting in Orlando, all of the six subsequent GMBIM meetings being held in Bloomington, Indiana. Today, thousands of biotechnology companies are in existence making great progress in the pharmaceutical and agricultural sectors. Hundreds of new genetically engineered compounds, produced in microbial, mammalian or insect cells, are in clinical trails and many are already being marketed. The field is booming with new technologies such as transgenic animals and plants, site-directed mutagenesis, combinatorial biosynthesis, gene therapy, antisense, abzymes, high-throughput screening, monoclonal antibodies, PCR and many more. Agricultural biotechnology has made great strides but unfortunately its progress is being delayed by political controversy. PMID- 11774000 TI - Old and new approaches used to identify gene products important for Saccharomyces cerevisiae cell wall biology. PMID- 11774001 TI - Engineering of complex polyketide biosynthesis--insights from sequencing of the monensin biosynthetic gene cluster. AB - The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifunctional enzymes, the modular Type I polyketide synthases (PKSs). Most of our current knowledge of such systems stems from the study of a restricted number of macrolide-synthesising enzymes. The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic evidence for the mechanism of oxidative cyclisation through which polyethers such as monensin are formed from the uncyclised products of the PKS. Two intriguing genes associated with the monensin PKS cluster code for proteins, which show strong homology with enzymes that trigger double bond migrations in steroid biosynthesis by generation of an extended enolate of an unsaturated ketone residue. A similar mechanism operating at the stage of an enoyl ester intermediate during chain extension on a PKS could allow isomerisation of an E double bond to the Z isomer. This process, together with epoxidations and cyclisations, form the basis of a revised proposal for monensin formation. The monensin PKS has also provided fresh insight into general features of catalysis by modular PKSs, in particular into the mechanism of chain initiation. PMID- 11774002 TI - Genetic approaches for controlling ratios of related polyketide products in fermentation processes. AB - Simple acyl thioesters are used as precursors for both the initiation and elongation steps in polyketide biosynthetic processes. Several structurally related polyketide products are sometimes made in these processes. These analogs are typically generated by a combination of two factors: availability of structurally similar biosynthetic precursors, and biosynthetic enzymes unable to effectively discriminate between them. Often, only one polyketide product is desired from a fermentation process, requiring a method to control the ratio of these different analogs. Preferential production of one desired analog is accomplished using random mutagenesis and manipulation of fermentation conditions. A genetic enzymatic understanding of polyketide biosynthesis, as well as the pathways that provide the relevant precursors, allows for a rational and more contemporary approach for control of analogs produced in fermentation processes. This approach involves genetic manipulation of either the pathways that provide pools of the acyl CoA thioester precursors, or the function/specificity of the appropriate biosynthetic enzymes. Reviewed herein are three such examples where these approaches have been carried out successfully with polyketide biosynthetic processes. PMID- 11774003 TI - The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis. AB - The hybrid peptide-polyketide backbone of bleomycin (BLM) is assembled by the BLM megasynthetase that consists of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. BlmIX/BlmVIII/BlmVII constitute a natural hybrid NRPS/PKS/NRPS system, serving as a model for both hybrid NRPS/PKS and PKS/NRPS systems. Sequence analysis and functional comparison of domains and modules of BlmIX/BlmVIII/BlmVII with those of nonhybrid NRPS and PKS systems suggest that (1) the same catalytic sites appear to be conserved in both hybrid NRPS-PKS and nonhybrid NRPS or PKS systems, with the exception of the KS domains in the hybrid NRPS/PKS systems that are unique; (2) specific interpolypeptide linkers may play a critical role in intermodular communication to facilitate transfer of the growing intermediates between the interacting NRPS and/or PKS modules; and (3) posttranslational modification of the BLM megasynthetase has been accomplished by a single PPTase with a broad substrate specificity toward the apo forms of both acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs). PMID- 11774004 TI - Characterization of the biosynthetic gene cluster for the oligosaccharide antibiotic, Evernimicin, in Micromonospora carbonacea var. africana ATCC39149. AB - Evernimicin (EV) belongs to the orthosomycin class of antibiotics and consists of several modified L- and D-deoxysugars containing unusual orthoester and glycosyl linkages and two orsellinic acid groups, one that is halogenated. The EV biosynthetic gene cluster from Micromonospora carbonacea var. africana ATCC39149 was localized by hybridization to a dTDP-D-glucose 4,6-dehydratase probe and a 120-kb region containing the EV biosynthetic cluster and surrounding regions has been sequenced. BLAST analysis has identified a type I polyketide synthase for orsellinic acid biosynthesis as well as enzymes required for L- and D deoxyglucose and D-deoxymannose synthesis. In addition, genes involved in glycosyltransfer and resistance were identified. Insertional mutations in several biosynthetic genes blocked EV production, indicating a role for these genes in EV biosynthesis. PMID- 11774005 TI - Structure and mechanism of chalcone synthase-like polyketide synthases. AB - Polyketide synthases (PKS) produce an array of natural products with different biological activities and pharmacological properties by varying the starter and extender molecules that form the final polyketide. Recent studies of the simplest PKS, the chalcone synthase (CHS)-like enzymes involved in the biosynthesis of flavonoids, anthocyanin pigments, and antimicrobial phytoalexins, have yielded insight on the molecular basis of this biosynthetic versatility. Understanding the structure-function relationship in these PKS provides a foundation for manipulating polyketide formation and suggests strategies for further increasing the scope of polyketide biosynthetic diversity. PMID- 11774009 TI - Neonatal resuscitation: in the public domain or private decision? PMID- 11774006 TI - Genes for the biosynthesis of spinosyns: applications for yield improvement in Saccharopolyspora spinosa. AB - Spinosyns A and D are the active ingredients in an insect control agent produced by fermentation of Saccharopolyspora spinosa. Spinosyns are macrolides with a 21 carbon, tetracyclic lactone backbone to which the deoxysugars forosamine and tri O-methylrhamnose are attached. The spinosyn biosynthesis genes, except for the rhamnose genes, are located in a cluster that spans 74 kb of the S. spinosa genome. DNA sequence analysis, targeted gene disruptions and bioconversion studies identified five large genes encoding type I polyketide synthase subunits, and 14 genes involved in sugar biosynthesis, sugar attachment to the polyketide or cross-bridging of the polyketide. Four rhamnose biosynthetic genes, two of which are also necessary for forosamine biosynthesis, are located outside the spinosyn gene cluster. Duplication of the spinosyn genes linked to the polyketide synthase genes stimulated the final step in the biosynthesis--the conversion of the forosamine-less pseudoaglycones to endproducts. Duplication of genes involved in the early steps of deoxysugar biosynthesis increased spinosyn yield significantly. PMID- 11774010 TI - Clavicle fracture in labor: risk factors and associated morbidities. AB - OBJECTIVE: Neonatal clavicle fracture has been previously reported to occur in association with shoulder dystocia, suggesting liability on behalf of the obstetrician. However, clavicle fracture is often inconsistently diagnosed, and shoulder dystocia commonly subjectively defined. Using a formal pediatric diagnosis protocol and an objective definition of shoulder dystocia, we sought to determine the incidence, antecedents, and associated morbidities of clavicle fracture and the potential association with shoulder dystocia. STUDY DESIGN: All deliveries at Harbor-UCLA Medical Center complicated by clavicle fracture from January 1996 to March 1999 were studied. Deliveries with clavicle fracture were compared to all vaginal deliveries during this period. RESULTS: Among 4297 deliveries, twenty-six were complicated by clavicle fracture (0.5%). Clavicle fracture was significantly associated with increased maternal age and birth weight greater than 4 kg, though not associated with shoulder dystocia or operative vaginal delivery. Clavicle fracture was associated with meconium passage and with neonatal orthopedic abnormalities. CONCLUSION: Neonatal clavicle fracture is associated with infant birth weight greater than 4 kg, but not with the occurrence of objectively defined shoulder dystocia. However, infants with clavicle fracture may be at increased risk for additional complications. PMID- 11774011 TI - Amniotic fluid Clara cell protein concentration in normal pregnancy, a marker of fetal airway growth or fetal lung maturation? AB - OBJECTIVE: To evaluate the relationship of Clara cell protein (CCP) in amniotic fluid (AF) with the lecithin/sphingomyelin (L/S) ratio, and the concentrations of saturated phosphatidylcholine (Sat PC) and surfactant protein A (SP-A). STUDY DESIGN: AF samples were obtained by amniocentesis from 98 pregnancies without conditions known to influence fetal lung maturation between 25 and 41 weeks of gestation. These samples were used for determinations of CCP, L/S ratio, Sat PC, and SP-A. Simple and multiple linear regressions were used to analyze the data. RESULTS: CCP in AF increased logarithmically with gestational age (R(2)=0.51, p=0.006). The L/S ratio (R(2)=0.41, p<0.001), and the concentrations of Sat PC (R(2)=0.26, p<0.001) and SP-A (R(2)=0.52, p<0.001) also increased with advancing gestation. Weak correlations of CCP with the L/S ratio (R(2)=0.22, p=0.009) and Sat PC (R(2)=0.12, p=0.004), but not with SP-A (R(2)=0.07, p=0.10), were found. Using multiple linear regressions, gestational age was the only predictor of CCP (F=10.9, R(2)=0.13, p=0.015). Conversely, gestational age, Sat PC, and SP-A accounted for most of the variation of the L/S ratio (F=34.7, R(2)=0.61, p=0.0001). CONCLUSION: CCP correlated very poorly with known and widely accepted indices of fetal lung maturation. The increasing concentration of CCP in AF throughout gestation probably reflects growth and development of the fetal airways. PMID- 11774012 TI - Effects of continuous positive airway pressure on diaphragm dimensions in preterm infants. AB - OBJECTIVE: The use of continuous positive airway pressure (CPAP) in the treatment of a variety of neonatal respiratory conditions is associated with improvement in arterial oxygen saturation, decreased long-term morbidity, and an overall improvement in infant survival. We reasoned that CPAP might change diaphragm length by increasing end-expiratory lung volume (EEV), but the extent to which this occurs has not been assessed. This study was designed to evaluate (1) the extent to which CPAP shortens the diaphragm and (2) the relationship of diaphragm thickness and excursion with arterial oxygen saturation in spontaneously breathing preterm infants. STUDY DESIGN: Ultrasonographically (7.5 MHz transducer), diaphragm thickness and diaphragm excursion were measured in 12 stable preterm infants [birth weight 1120+/-225 g (mean+/-SD); study weight 1187+/-400 g; gestational age 29+/-1 week; postnatal age 10+/-8 days, six males and six females] at three levels of CPAP [1-3, 4-6, and 7-9 cm H(2)O (low, medium, and high, respectively)]. Heart rate, respiratory rate, and arterial oxygen saturation were simultaneously recorded. RESULTS: We found that diaphragm thickness and arterial oxygen saturation increased, and diaphragm excursion decreased significantly at higher levels of CPAP (p<0.05). The shortening of the diaphragm at the high levels of CPAP, calculated from the increase in diaphragm thickness, was 36% at EEV and 31% at end-inspiratory volume. CONCLUSION: We conclude that the improvement in arterial oxygen saturation with CPAP occurred despite the presence of a shorter and a less mobile diaphragm, and that other physiological and mechanical alterations accompanying the application of CPAP offset its negative effects on diaphragm function. We speculate that with excessive CPAP, however, diaphragm dysfunction along with the previously described adverse hemodynamic effects may outweigh its benefits on oxygenation. PMID- 11774013 TI - Complications in tunneled CVL versus PICC lines in very low birth weight infants. AB - OBJECTIVE: Comparison of complications associated with tunneled central venous lines (TCVLs) versus peripherally inserted central catheters (PICCs) in infants <1500 g. STUDY DESIGN: A retrospective cohort study at a university medical center. A total of 96 catheters were placed in 60 infants between 4/94 and 3/99. A retrospective review of these infants' medical record was done to review associated complications of catheter placement. RESULTS: Both groups had similar weights and gestational ages. The duration of catheterization was 28 days in TCVLs and 11 days in PICCs (p<0.05). Total, infectious, and mechanical complications between the two groups were similar. Survival function estimates showed no difference between the two groups up to the 15th day of catheterization. CONCLUSION: There is no difference in efficacy or associated complications between the two groups. If one could anticipate needing a catheter longer than 15 days, then a TCVL might be the better choice. PMID- 11774014 TI - Reference ranges for thyroid function tests in premature infants beyond the first week of life. AB - OBJECTIVES: To establish reference ranges for the more sensitive assays of thyrotropin and the best available assays of free thyroxine in premature infants after the first week of life. STUDY DESIGN: Free thyroxine measurements by direct equilibrium dialysis and thyrotropin measurements by third generation immunometric assay were measured in 120 healthy premature infants 25 to 36 weeks' gestation at birth and every 3 weeks until hospital discharge. Infants were stratified by postconceptional age. Differences in free thyroxine and thyrotropin levels among groups were determined by ANOVA. Correlations between hormone measurements and gestational and postnatal ages were sought by linear regression analysis. Reference ranges were determined as arithmetic (free thyroxine) and geometric (thyrotropin) mean+/-2 SD ranges. RESULTS: From 120 infants, 164 samples were obtained and grouped by postconceptional age at sampling. Free thyroxine was not different among postconceptional age groups and did not correlate with gestational or postnatal age. The free thyroxine reference range based on these data was 10 to 33 pmol/l (0.8 to 2.6 ng/dl). Thyrotropin did not correlate with gestational age. There was a clinically trivial but statistically significant (r(2)=0.03, p<0.05) correlation of thyrotropin with postnatal age. The thyrotropin reference based on these data was 0.8 to 12 mU/l. CONCLUSIONS: Free thyroxine was closely regulated in these premature infants and levels were similar to those in older children and adults, once the natal surge in thyrotropin has subsided. After the first week of life a single range for each hormone appeared appropriate for all premature infants until 40 weeks postconceptional age. PMID- 11774015 TI - Meconium-stained amniotic fluid and neonatal morbidity in near-term and term deliveries with acute histologic chorioamnionitis and/or funisitis. AB - OBJECTIVE: To determine the incidence of meconium-stained amniotic fluid (MSAF) and neonatal morbidity in near-term and term deliveries with histologic acute chorioamnionitis and/or funisitis compared to those with normal placental histology. STUDY DESIGN: In a retrospective case-control design, we compared the incidence of MSAF and neonatal outcome in 45 cases of acute histologic chorioamnionitis and/or funisitis with 89 cases of normal placental histology. We reviewed the obstetric and neonatal records for perinatal complications and neonatal morbidity. RESULTS: Mean birthweights (3372+/-473 vs 3287+/-518 g) were similar in infants born to mothers with histologic chorioamnionitis and/or funisitis compared to infants born to mothers with normal placental histology. The incidence of MSAF was significantly higher in the group with acute chorioamnionitis/funisitis (p<0.05). Similarly, the incidence of admissions to newborn intensive care unit, respiratory distress, meconium aspiration syndrome, and presumed sepsis was also significantly higher (p<0.05) in this group. CONCLUSION: The incidence of MSAF and neonatal morbidity is higher in the presence of acute inflammation of placental membranes. The presence of meconium in the amniotic fluid should alert the physician to the potential for infection and increased neonatal morbidity. PMID- 11774016 TI - Bad cases make bad law: HCA v. Miller is not a guide for resuscitation of extremely premature newborns. PMID- 11774017 TI - Neonatal varicella. AB - Neonatal varicella is mostly caused by maternal chickenpox acquired during the last 3 weeks of pregnancy. Transplacentally transmitted infections occur in the first 10 to 12 days of life, whereas chickenpox after that time is most likely acquired by postnatal infection. If the mother develops rash between days 4 and 5 antepartum to day 2 postpartum, generalized neonatal varicella leading to death occurs in up to 20% of affected cases. Neonatal chickenpox within the first 4 days after birth has usually been found to be mild. A fatal outcome has been reported in 23% of cases if neonatal chickenpox occurs between 5 and 10 to 12 days of age. Serological methods have been widely used to confirm clinical diagnosis. For rapid virological diagnostics, amplification of viral DNA in skin swabs by polymerase chain reaction is the method of choice. To prevent severe neonatal chickenpox, passive immunization is indicated. If varicella occurs, acyclovir treatment has to be administered promptly. PMID- 11774018 TI - Fracture of lower femoral epiphysis in an infant at birth: a rare obstetrical injury. AB - We report a case of rare birth injury leading to physeal fracture after a routine cesarean delivery. Because plain radiographics are often normal, therefore these physeal fractures usually present a diagnostic challenge in the newborn. In this case, ultrasonography and magnetic resonance imaging were helpful in making an early accurate diagnosis. The infant received prompt treatment and the physeal fracture healed uneventfully. Physeal fractures should be included in the birth injuries following routine cesarean delivery. PMID- 11774019 TI - Decompression of multiple pneumatoceles in a premature infant by percutaneous catheter placement. AB - Pneumatoceles due to acquired localized overinflation as a form of pulmonary interstitial emphysema are complications of advanced bronchopulmonary dysplasia. Different ventilation modes, selective bronchial intubation, balloon obstruction of the affected bronchus and steroids have been reported with success. Lobectomy has also been used. We present a premature infant with multiple large pneumatoceles causing respiratory compromise. In our case percutaneous decompression under fluoroscopy guidance resulted in a permanent cure. PMID- 11774020 TI - Successful use of topical nitroglycerine in ischaemia associated with umbilical arterial line in a neonate. AB - Ischaemic changes associated with umbilical arterial cannulation is an important cause of neonatal morbidity in the NICU. We report successful use of topical nitroglycerine in an infant with ischaemic changes over the right buttock following insertion of an umbilical arterial catheter. PMID- 11774021 TI - Severe intrauterine herpes simplex disease with placentitis in a newborn of a mother with recurrent genital infection at delivery. AB - We present a case of fatal herpes simplex type 2 (HSV-2) in a premature infant born to a mother diagnosed with recurrent HSV-2, based on history and HSV serology results. It was clinically evident at delivery, and subsequently confirmed by laboratory studies that the infant was infected before delivery. There was histopathologic evidence of placentitis and chorioamnionitis upon examination of the placenta and fetal membranes. This case illustrates a relatively uncommon complication of recurrent genital herpes at delivery- intrauterine transmission to the fetus from a primary episode during pregnancy. PMID- 11774022 TI - Pfeiffer syndrome, type II. PMID- 11774023 TI - Solitary hepatic hemangioendothelioma with extensive cystic necrosis and markedly elevated alpha-fetoprotein. PMID- 11774028 TI - Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. AB - The matrix metalloproteinase matrilysin (MMP-7) has been demonstrated to contribute to tumor development. We have shown previously that members of the TNF family of apoptosis-inducing proteins are substrates for this enzyme, resulting in increased death pathway signaling. The goal of the current study was to reconcile the proapoptotic and tumor-promoting functions of matrilysin. In the human HBL100 and murine NMuMG cell lines that represent early stages of tumor progression and that express both Fas ligand and its receptor, exposure to matrilysin results in cell death that can be blocked by FasL neutralizing antibodies. Constitutive expression of matrilysin in these cell lines selects for cells with reduced sensitivity to Fas-mediated apoptosis as demonstrated both with a receptor-activating antibody and with in vitro activated splenocytes. Matrilysin-expressing cells are also significantly less sensitive to chemical inducers of apoptosis. We propose that the expression of matrilysin that has been reported at early stages in various tumor types can act to select cells with a significantly decreased chance of removal due to immune surveillance. As a result, these cells are more likely to acquire additional genetic modifications and develop further as tumors. PMID- 11774030 TI - Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. AB - A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR)-dependent nuclear factor of activated T cells (NFAT)-mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP)] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OFI and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [(124)I]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs. PMID- 11774029 TI - Bromelain reversibly inhibits invasive properties of glioma cells. AB - Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, and fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, and invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that alpha3 and beta1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, and translational attenuation. PMID- 11774031 TI - Magnetic labeling of activated microglia in experimental gliomas. AB - Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS. PMID- 11774032 TI - Hypoxia and VEGF mRNA expression in human tumors. AB - High expression of circulating plasma vascular endothelial growth factor (VEGF) in patients with cancer is an indicator of poor treatment response. Similarly, hypoxia in tumors, as measured by oxygen needle electrodes, has been found to predict for tumor-treatment failure. These two predictors may be related because hypoxia is a potent stimulator of VEGF expression in vitro. However, the demonstration of a relationship between hypoxia and VEGF in human tumors has, to date, been indirect or even negative. The purpose of this study was to test whether this unexpected result was caused by factors unique to human tumors, or whether the prior results could have been influenced by the known complexities of VEGF regulation. Therefore, we undertook a direct assessment of VEGF induction in human tumors using in situ hybridization and compared its distribution with that of hypoxia, as measured by the distribution of adducts of the hypoxia marker EF5. The distribution of both markers was assessed in relationship to the distribution of blood vessels, as measured by antibodies to CD31. Our hypothesis was that VEGF mRNA and hypoxia would colocalize, assuming that detectability of the former was not limiting. Four squamous cell carcinomas, three sarcomas and one glioblastoma multiforme were studied. When VEGF mRNA signal was detectable, its maxima colocalized with regional maxima of EF5 binding. The strongest levels of both signals were sometimes adjacent to regions of tissue necrosis. However, we were unable to predict absolute levels of EF5 binding based on absolute levels of VEGF mRNA. Conversely, for all tumors studied, regions with relatively low levels of EF5 binding had relatively low or undetectable VEGF mRNA. We found moderate EF5 binding in some keratinized cells but VEGF mRNA was not expressed by these differentiated cells. The paradigm that hypoxia and VEGF expression are linked in human tumors is supported by the data presented herein. A better understanding of the biology behind VEGF expression, including its modulation by hypoxia, is important for optimizing its use as a prognostic indicator and/or modulating its presence with biologic therapies. PMID- 11774033 TI - Interleukin-1beta-induced promatrilysin expression is mediated by NFkappaB regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP. AB - Previously, our laboratory showed that interleukin-1beta (IL-1beta) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1beta-induced promatrilysin expression is mediated by an indirect mechanism that requires nuclear factor Kappa B (NFkappaB)-dependent synthesis of IL-6. Inhibition of protein synthesis with cycloheximide blocked IL-1beta-mediated induction of matrilysin mRNA suggesting that synthesis of one or more additional factors is required for IL-1beta-induced promatrilysin protein expression. Blockage of NFkappaB transactivation activity abrogated IL-1beta-induced promatrilysin expression to baseline levels suggesting that NFkappaB transactivation activity is necessary. Inhibition of IL-6 activity attenuated IL-1beta-induced promatrilysin, but not NFkappaB transactivation activity indicating that IL-6 acts downstream of NFkappaB in potentiation of IL-1beta-mediated promatrilysin expression. Inhibition of protein synthesis with cycloheximide did not alter IL-6 induced induction of matrilysin mRNA indicating that, contrary to the mechanism by which IL-1beta regulates promatrilysin expression, IL-6-mediated matrilysin mRNA expression does not require new protein synthesis. Transient transfection with dominant negative STAT3 inhibited IL-1beta- and IL-6-induced promatrilysin. These data provide evidence that NFkappaB-mediated IL-6 synthesis is required for IL-1beta-induced promatrilysin expression, and IL-6 signaling through STAT3 plays a role in IL-1beta-induced promatrilysin expression. PMID- 11774034 TI - Overexpressed genes/ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells. AB - 17q23 is a frequent site of gene amplification in breast cancer. Several lines of evidence suggest the presence of multiple amplicons on 17q23. To characterize distinct amplicons on 17q23 and localize putative oncogenes, we screened genes and expressed sequence tags (ESTs) in existing physical and radiation hybrid maps for amplification and overexpression in breast cancer cell lines by semiquantitative duplex PCR, semiquantitative duplex RT-PCR, Southern blot, and Northern blot analyses. We identified two distinct amplicons on 17q23, one including TBX2 and another proximal region including RPS6KB1 (PS6K) and MUL. In addition to these previously reported overexpressed genes, we also identified amplification and overexpression of additional uncharacterized genes and ESTs, some of which suggest potential oncogenic activity. In conclusion, we have further defined two distinct regions of gene amplification and overexpression on 17q23 with identification of new potential oncogene candidates. Based on the amplification and overexpression patterns of known and as of yet unrecognized genes on 17q23, it is likely that some of these genes mapping to the discrete amplicons function as oncogenes and contribute to tumor progression in breast cancer cells. PMID- 11774035 TI - Green fluorescent protein is a suitable reporter of tumor hypoxia despite an oxygen requirement for chromophore formation. AB - The oxygen requirement for chromophore formation potentially limits the use of green fluorescent protein as a reporter under hypoxic conditions. In the light of this, the applicability of a hypoxia-responsive enhanced green fluorescent protein (EGFP)-based system to the measurement of tumor hypoxia was tested in human HT 1080 fibrosarcoma cells stably transfected with a destabilized EGFP vector containing the hypoxia-responsive 5HRE-hCMVmp promoter or, as a positive control, the strong constitutive CMV promoter. After various schedules of hypoxia and reoxygenation, EGFP fluorescence of live cells was assessed by flow cytometry, and protein levels were analyzed by Western blot. Fluorescence of CMV promoter positive control cells dropped to 38+/-5% of aerobic levels after 12 hours at <0.02% oxygen, but was unaffected by higher oxygen concentrations. Following 12 hours at <0.02% oxygen, cells transfected with the hypoxia responsive vector exhibited maximum fluorescence after 4 hours of subsequent reoxygenation, reaching 68+/-2% of the levels in CMV promoter controls under aerobic conditions. With such reoxygenation, these cells exhibited a constant increase in fluorescence between 2% and <0.02% oxygen. EGFP chromophore formation is only affected by near-anoxic oxygen concentrations. The correlation of fluorescence and oxygen concentration is restored by a 4-hour reoxygenation period due to oxidation of pre-synthesized EGFP and a delayed increase in EGFP protein synthesis. PMID- 11774041 TI - [Ewald Koob to his 75th Birthday] PMID- 11774042 TI - ? PMID- 11774043 TI - ? PMID- 11774044 TI - ? PMID- 11774038 TI - Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1. AB - Bcl-2 is a critical suppressor of apoptosis that is overproduced in many types of cancer. Phosphorylation of the Bcl-2 protein is induced on serine residues in tumor cells arrested by microtubule-targeting drugs (paclitaxel, vincristine, nocodazole) and has been associated with inactivation of antiapoptotic function through an unknown mechanism. Comparison of a variety of pharmacological inhibitors of serine/threonine-specific protein kinases demonstrated that the cyclin-dependent kinase inhibitor, flavopiridol, selectively blocks Bcl-2 phosphorylation induced by antimicrotubule drugs. Bcl-2 could also be coimmunoprecipitated with the kinase Cdc2 in M-phase-arrested cells, suggesting that Cdc2 may be responsible for phosphorylation of Bcl-2 in cells treated with microtubule-targeting drugs. Examination of several serine-->alanine substitution mutants of Bcl-2 suggested that serine 70 and serine 87 represent major sites of Bcl-2 phosphorylation induced in response to microtubule-targeting drugs. Both these serines are within sequence contexts suitable for proline-directed kinases such as Cdc2. Phosphorylated Bcl-2 protein was discovered to associate in M-phase arrested cells with Pin1, a mitotic peptidyl prolyl isomerase (PPIase) known to interact with substrates of Cdc2 during mitosis. In contrast, phosphorylation of Bcl-2 induced by microtubule-targeting drugs did not alter its ability to associate with Bcl-2 (homodimerization), Bax, BAG1, or other Bcl-2-binding proteins. Since the region in Bcl-2 containing serine 70 and serine 87 represents a proline-rich loop that has been associated with autorepression of its antiapoptotic activity, the discovery of Pin1 interactions with phosphorylated Bcl-2 raises the possibility that Pin1 alters the conformation of Bcl-2 and thereby modulates its function in cells arrested with antimicrotubule drugs. PMID- 11774045 TI - [Transplantation medicine]. PMID- 11774036 TI - TRAIL/Apo-2L: mechanisms and clinical applications in cancer. AB - TNF-related apoptosis-inducing ligand (TRAIL/APO-2L) is a member of the TNF family that promotes apoptosis by binding to the transmembrane receptors TRAIL R1/DR4 and TRAIL-R2/DR5. Its cytotoxic activity is relatively selective to the human tumor cell lines without much effect on the normal cells. Hence, it exerts an antitumor activity without causing toxicity, as apparent by studies with several xenograft models. This review discusses the intracellular mechanisms by which TRAIL induces apoptosis. The major pathway of its action proceeds through the formation of DISC and activation of caspase-8. The apoptotic processes, therefore, follow two signaling pathways, namely the mitochondrial-independent activation of caspase-3, and mitochondrial-dependent apoptosis due to cleavage of BID by caspase-8, the formation of apoptosomes, and activation of caspase-9 and the downstream caspases. Bcl-2 and Bcl-X(L) have no effect on TRAIL-induced apoptosis in lymphoid cells, whereas these genes block or delay apoptosis in nonlymphoid cancer cells. TRAIL participates in cytotoxicity mediated by activated NK cells, monocytes, and some cytotoxic T cells. Hence, TRAIL may prove to be an effective antitumor agent. In addition, it may enhance the effectiveness of treatment with chemotherapeutic drugs and irradiation. Nontagged Apo-2L/TRAIL does not cause hepatotoxicity in monkeys and chimpanzees and in normal human hepatocytes. Thus, nontagged Apo-2L/TRAIL appears to be a promising new candidate for use in the treatment of cancer. PMID- 11774046 TI - [Psychosomatic medicine and transplant patients - what is known and what is needed]. AB - Psychosomatic research has resulted in a huge pool of data concerning the psychic state of transplant patients and their relatives during the course of organ transplantation. It has been possible as well to describe important psychosocial prognostic factors, influencing both somatic and psychosocial outcome after transplantation. The following review article gives an overview of the results that are relevant to daily psychosomatic practice in transplantation medicine. It mainly deals with the problems of transplant patients and their relatives. The special issues of living related organ donation cannot be subject of this review. Finally the article tries to show perspectives for the development of psychosomatic interventions in the treatment of organ transplant patients. PMID- 11774047 TI - [Donor risk in living-related liver transplantation - the surgeon's point of view]. AB - Living-related liver transplantation is a successful clinical approach to overcome organ shortage in hepatic transplantation. Possible advantages for the recipient of a living-donor transplant are a much shorter waiting period until transplantation and an almost elective time of operation which results in a decreased operative risk. Furthermore graft function of a living-related transplant is better than in cadaveric transplantation because of the shorter ischemic time and a careful examination of graft quality before organ donation. Removal of even more than 50 % of liver volume during the donor operation does not lead to an impairment of liver function in the organ donor. Intraoperative blood loss can usually be managed by re-transfusion of donor's own blood. Postoperative morbidity is about 10 - 15 % depending on the extent of the removed liver lobe. Most frequent postoperative complications are biliary leckages, wound infections and gastric/duodenal ulcerations. Up till now in more than 1000 living related liver donations only three deaths occured due to thromboembolic and septic complications (< 0,3 %) (until 12/1998). PMID- 11774048 TI - [Living organ donation vs. cadaveric donation - study of liver transplanted children and their families]. AB - There is only scarce information on the quality of life of child recipients of liver transplants and their families. Particularly children with a living related graft and their families never have been compared to children who received a cadaveric graft and their families. We investigated the following issues in our study: How do parents and children from participating families rate their strain, their quality of life and their relationships within their family? Do families with a living - related donor differ from those with a cadaveric donor? What do living donors and their partners think about the donation retrospectively? The study was conducted with 106 participants from 50 families (42 mothers, 40 fathers, and 24 children older than 6 years). In 20 of these families, a living transplantation had been performed. Participants were interviewed and asked to fill out several questionnaires. School-aged children with a liver transplant show good social integration among their peers and in school. The child's disease, however, has a great impact on the family. Family members show a reduction in social contact, and an increase in marital crises, and problematic relations amongst siblings. Families in which a cadaveric graft was performed, are less satisfied with life, and show more symptoms of exhaustion. Every family studied possessed or acquired - a high degree of internal or external coping resources. Living - related donors tried hard to obtain an understanding of the medical context. The partner, rather than the donor himself, feels anxious before the donation. The limited time available for the decision to donate is not perceived by the donors to be critical. Ten percent of living donors feel "a little" that their health is affected. The decision to donate is supported "strongly" or "very strongly" by the partners in 80 % of the cases. A possible strain on the child through the expectation of gratitude by the donor is stated by 20 %. All of the donors agree that if they were to be asked today, they would donate again, only one of the partners raised objections. In summary, as a retrospective pilot study, this study primarily generates hypotheses rather than testing them and helps to develop research tools for the field. Results suggest that a psychological support be made available both prior to and following the operation, not only for the children but also for their families, with particular attention to the partners of the living donors and the siblings of the affected children. PMID- 11774049 TI - [Parent-child relationship in families with liver-transplantated infants]. AB - Due to progress in transplantation medicine and especially thanks to the possibility of transplantation of a liver lobe from a living donor - usually one parent - even very small children with end-stage liver diseases are transplanted nowadays. But there is little research on how parents cope with this specific situation facing the death of their baby without transplantation during the period of transition to parenthood, how family-relationships and bonding develop after transplantation, how the infants develop mentally and emotionally and what specific psychosocial help these families would need to prevent future problems. Stimulated by clinical experiences with families with liver-transplanted infants, a pilot study with families before liver-transplantation was conducted. The aim of the study was to determine methods of infant research suitable for this clinical population. Based on case-vignettes of the interviews and the clinical work with these families, questions as to transition to parenthood, bonding and liver-transplantation by donation of a lobe of one parent's liver are discussed. PMID- 11774050 TI - Pearls and pitfalls of ethical issues in neurology. AB - The growth of bioethics as a practical, meaningful player in the arena of health care has paralleled that of clinical neurology not only in time but also in interaction between the two disciplines. Almost every advance in neurology has spawned an ethical dilemma, the unraveling of which has brought new insights to both fields of endeavor. The myriad ways in which this parallel growth has touched one clinical neurologist, the persons with whom he has been privileged to work, and those for whom they have cared is offered in reflection on the meaning of ethics, the essence of concepts such as "brain death," the pain of truth telling, the complexity of informed consent, the societal dimension of the "vegetative state," and finally, even the business of medicine. Should readers not find any pearls of wisdom in this offering, the author can at least hope it will prevent them from falling into the same pits. PMID- 11774051 TI - Teaching in the field: the model of a one-day trip to an outreach clinic. AB - A trip to an outreach clinic in a 15-passenger van is presented as part of the answer to the forces negatively affecting the practice of academic medicine today. Any subspecialist in a medical center can use the model if a community can be identified that has a hospital or clinic building able to host the university group. County- or state-funded facilities are well suited to a periodic clinic, and public health nurses are well trained in their management. The Muscular Dystrophy Association is a private supporter of clinics like this, allowing specialty doctor visits close to home for patients with disabling weakness who might otherwise be excluded from our increasingly restricted health care system. PMID- 11774052 TI - Pearls and pitfalls of headache. AB - Headache is one of the most common complaints confronting neurologists. This article illustrates through case studies both some of the rare and some of the commonly challenging aspects of diagnosis and management of headache. Each case is followed by a brief overview of the topic. The reader should have an appreciation of the importance of historical clues to diagnosis and specific management for atypical headache entities. PMID- 11774054 TI - The ten-minute examination of the dizzy patient. AB - Dizziness and postural instability are common presenting complaints in patients seen in otolaryngology practice. Unfortunately, these patients frequently do not receive optimal evaluation and therapy because of the difficulty in obtaining a thorough yet pertinent history and the perceived complexity of the physical examination. Over the last 10 years, we have utilized a standardized approach to evaluation of the dizzy patient that is user friendly and maximizes the time and effort spent by the clinician. First, a thorough history is taken from the patient in two forms: (1) a specially designed questionnaire filled out well before the examination and (2) a direct interview using the answers on the questionnaire as a guide. During the physical examination, emphasis is placed on the following subtests: (1) spontaneous nystagmus; (2) central oculomotor function; (3) the vestibulo-ocular reflex (VOR) battery--headshake, head thrust, dynamic visual acuity, and Hallpike positioning; (4) coordination; (5) posture; (6) gait; and (7) special examinations. This neurotologic examination is completed in about 10 minutes and is performed as a battery of tests following the routine otolaryngologic and/or neurologic examination. We feel that this test sequence is thorough yet easy to perform and ideally will demystify the examination of these challenging patients. PMID- 11774053 TI - Polysomnographic assessment of spells in sleep: nocturnal seizures versus parasomnias. AB - A dilemma can arise when attempting to distinguish a nocturnal seizure from a parasomnia because both phenomena can be characterized by a general increase in motor and autonomic activity with a transient reduction in the level of consciousness. An additional problem is that an accurate clinical diagnosis generally relies heavily on a detailed history. As sleep related disorders occur at a time when the patient is not fully cognizant, polysomnographic analysis can on occasion supplement for the intrinsic paucity of detailed history. Simultaneously, correlating the clinical and polysomnographic analysis immediately prior to, during, and following an event of interest, can be helpful in differentiating nocturnal seizures from parasomnias. PMID- 11774055 TI - Pearls and pitfalls in the intensive care management of Guillain-Barre syndrome. AB - Approximately one third of patients with Guillain-Barre syndrome (GBS) need to be admitted to the intensive care unit (ICU) because of respiratory failure. A significant proportion of patients require ICU admission because of dysautonomia or because of medical or iatrogenic complications. Recognition of the clinical manifestations and the paraclinical findings in patients with neuromuscular respiratory failure is essential to ensure mechanical ventilation promptly. In the ICU, attention to positioning, nutrition, analgesia, and psychological support are crucial. Recognition of autonomic dysfunction and of the rare need for intervention is important to avoid iatrogenic complications. Prognosis determination in GBS is based on the clinical history, epidemiological factors, and neurologic examination. PMID- 11774056 TI - Pearls and pitfalls in the approach to patients with neurotoxic syndromes. AB - Neurotoxins are an important cause of neurologic disorders. A vast number of potentially neurotoxic compounds exist, including prescription drugs, illicit substances, and exposures through the workplace, residence, hobbies, and the environment. Effects of neurotoxins can mimic neurologic illnesses; therefore, it is important to consider neurotoxins in the differential diagnosis of any patient with neurological dysfunction. Paramount to the diagnosis of a possible neurotoxic syndrome is establishing causation. This can be done by a systematic approach utilizing principles in epidemiology and applying them to the individual patient. This approach is discussed in the following article in an attempt to bring structure to solving problems in a complex area of medicine. PMID- 11774057 TI - Pearls and pitfalls of clinical trial investigation: should I get involved in the drug development process? AB - The revolution in neurological therapeutics means that an increasing number of neurologists will have the opportunity to participate in a drug development process that is long and complicated. The opportunity provides challenges as well as rewards, and should be undertaken only after thoughtful review of the Clinical Investigator's Brochure and protocol. Key questions that the neurologist should address prior to participation are reviewed herein. PMID- 11774058 TI - Pearls and pitfalls in the diagnosis and management of neuromuscular junction disorders. AB - Myasthenia gravis (MG) is a common autoimmune disorder characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor. Patients present with variable degrees and distribution of fluctuating weakness, at times life-threatening. Clinical manifestations, establishment of diagnosis, the natural history of MG, and therapeutic options are herein reviewed with an emphasis on pearls and pitfalls of clinical relevance. Far less common is Lambert Eaton syndrome (the myasthenic syndrome), another autoimmune disorder due to the presence of antibodies directed against the PQ-type voltage-gated calcium channels. Clinical features and treatment issues of these and other disorders of neuromuscular transmission are reviewed. PMID- 11774059 TI - Variability in the response of HDL cholesterol to exercise training in the HERITAGE Family Study. AB - In the HERITAGE Family Study, 675 sedentary, healthy, white and black men and women, aged 17 to 65 years, performed 20 weeks of supervised cycle ergometer exercise at the same relative intensity and weekly volume. As a group, subjects had normal mean baseline lipid levels for North Americans with the exception of below average high density lipoprotein cholesterol (HDL-C) levels. A significant mean increase in plasma HDL-C of 3.6 % was observed; however, there was marked variability in responsiveness to training, ranging from a mean 9.3 % decrease in Quartile 1 of HDL-C response to a mean 18 % increase in Quartile 4 (P < 0.0001 by ANOVA). Parallel changes in HDL(2)-C and HDL(3)-C, apolipoprotein A-I levels, and lipoprotein lipase activity were noted across quartiles. The change in HDL-C across quartiles was inversely related to baseline HDL-C (p < 0.0001) and to changes with training in plasma triglycerides (p = 0.0007). No significant differences in HDL-C response were observed across quartiles by sex, race, age, or increase in VO(2)max with training; however, weak positive associations were observed with age-adjusted education level and with reduction in abdominal fat and increase in VO(2)max at the ventilatory threshold following training. Multivariate regression analysis including baseline variables and training responses only accounted for 15.5 % of the variability in the HDL-C response to training. Thus, marked variability was found in the HDL-C response to the same endurance exercise training stimulus with only a modest amount of the response predictable by identified nongenetic factors. PMID- 11774060 TI - Effect of Vitamin C and E supplementation on biochemical and ultrastructural indices of muscle damage after a 21 km run. AB - This study investigated whether 4 weeks of daily supplementation with 500 or 1000 mg of Vitamin C and 500 or 1000 IU of Vitamin E could modify biochemical and ultrastructural indices of muscle damage following a 21 km run. Fifteen experienced male distance runners were divided into two groups (vitamin or placebo) and received supplementation for four weeks before completing the first 21 km run in as fast a time as possible. A four-week "washout" period followed before the subjects crossed over and received the alternate supplement for the next four weeks. They then completed a second 21 km run. Before, immediately after and 24 h after each run venous blood samples were taken and analysed for serum creatine kinase, myoglobin, malondialdehyde and vitamin C and E (before samples only) concentrations. A subgroup of six subjects also had muscle biopsy (gastrocnemius) samples taken 24 h before and 24 h after each 21 km run, which were later analysed by electron microscopy. The two dosages of supplementation produced similar results, so a single vitamin group was formed for further analysis of results. Significant increases (p < 0.05) in creatine kinase and myoglobin, but not in malondialdehyde, were found post-run in both groups. However, no significant differences were found between the vitamin and placebo groups for creatine kinase, myoglobin and malondialdehyde concentrations recorded after the 21 km runs. A qualitative ultrastructural examination of pre-run muscle samples revealed changes consistent with endurance training, but little further change was seen after the 21 km run in either the vitamin or placebo groups. It was concluded that vitamin C and E supplementation (500 or 1000 mg or IU per day) for four weeks does not reduce either biochemical or ultrastructural indices of muscle damage in experienced runners after a half marathon. PMID- 11774061 TI - The ratio HLa : RPE as a tool to appreciate overreaching in young high-level middle-distance runners. AB - The purpose of the present investigation was to study the effects of eight weeks of intensive training at the beginning of the athletic season on perceived exertion and on the ratio of blood lactate concentration to ratings of perceived exertion (HLa : RPE) in young runners. Eight high-level middle-distance runners performed two exhausting exercises on an indoor track before and after eight weeks of training. The first test was an incremental exercise to determine their maximal oxygen uptake (VO(2) max), the velocity associated with VO(2) max (vVO(2) max), the velocity of the lactate concentration threshold (vLT) and the velocity delta 50 (vDelta50 : the velocity halfway between vVO(2) max and vLT). The second test was a constant-load all-out run at vDelta50 to determine the time to exhaustion at this intensity (tlim vDelta50). There were five training sessions a week with interval training twice a week. After eight weeks of training, vVO(2) max, vLT and tlim vDelta50 were not significantly different. The athletes perceived exercise as being harder after training than before at a same given relative velocity in the incremental test. During the all-out run at vDelta50, they felt that, at the same given relative time, they could endure less after than before training. Moreover, the HLa : RPE ratio was significantly lower after intensive interval-training performed immediately after the holidays. Consequently, two interval-training sessions per week would induce an overreaching state that is not yet characterized by a decrease in performance and physiological values whereas perceived exertion (RPE, ETL) and especially the HLa : RPE ratio allows the detection of changes in young high-level middle-distance runners. PMID- 11774062 TI - Effect of ramp slope on ventilation thresholds and VO2peak in male cyclists. AB - This study investigated the effect of 10 W*min(-1) (Slow ramp, SR), 30 W*min(-1) (Medium ramp, MR) and 50 W*min(-1) (Fast ramp, FR) exercise protocols on assessments of the first (VT1) and second (VT2) ventilation thresholds and peak oxygen uptake (VO(2)peak) in 12 highly-trained male cyclists (mean +/- SD age = 26 +/- 6 yr). Expired gas sampled from a mixing chamber was analyzed on-line and VT1 and VT2 were defined as two break-points in 20-s-average plots of pulmonary ventilation (V(E)), ventilatory equivalents for O(2) (V(E)/VO(2)) and CO(2) (V(E)/VCO(2)), and fractions of expired O(2) (F(E)O(2)) and CO(2) (F(E)CO(2)). Arterialized-venous blood samples were analyzed for blood-gas and acid-base status. VO(2)peak was significantly lower (p < 0.05) for SR (4.65 +/- 0.53 l small middle dot min(-1)) compared to MR (4.89 +/- 0.56 l *min(-1)) and FR (4.88 +/- 0.57 l *min(-1)) protocols. CO(2) output and blood PCO(2) were lower (p < 0.05), and V(E)/VCO(2) was higher (p < 0.05), above VT1 for SR compared to MR and FR protocols. No significant differences were observed among the protocols for VO(2), % VO(2)peak, V(E), plasma lactate ([La(-)]) and blood hydrogen ion concentration ([H(+)]), and heart rate (HR) values at VT1 or VT2. The work rate (WR) measured at VT1, VT2 and VO(2)peak increased (p < 0.05) with steeper ramp slopes. It was concluded that, in highly-trained cyclists, assessments of VT1 and VT2 are independent of ramp rate (10, 30, 50 W*min(-1)) when expressed as VO(2), % VO(2)peak, V(E), plasma [La(-)], blood [H(+)] and HR values, whereas VO(2)peak is lower during 10 W*min(-1) compared to 30 and 50 W*min(-1) ramp protocols. In addition, the WR measured at VT1, VT2 and VO(2)peak varies with the ramp slope and should be utilized cautiously when prescribing training or evaluating performance. PMID- 11774063 TI - The efficacy of ergometry determined heart rates for flatwater kayak training. AB - The aim of this study was to investigate the use of incremental ergometry determined heart rate training intensities for the control of kayak ergometer and open water kayak training. Eight well-trained male kayakers completed a maximal incremental exercise test on an air-braked kayak ergometer for the determination of LT(1) (the power output at which blood lactate concentration increased by > or = 1 mmol x L(-1)), the associated heart rate (HR-LT(1)), VO(2)peak, maximal heart rate and maximal aerobic power. Subjects then performed 20 min trials of kayak ergometry (E), open water kayaking in a single kayak (K1) and open water kayaking in a four-seat kayak (K4) at HR-LT(1). During the three trials, heart rate was continuously measured, and blood lactate concentration, rating of perceived exertion (RPE) and stroke rate were determined every 5 min. In all trials, exercise at HR-LT(1) resulted in stable blood lactate concentrations and a stable RPE. Comparison of the three trials demonstrated that the only difference was for RPE, which was lower in (K4) than in (E), (p < 0.05). The results demonstrate that the prescription of HR-LT(1) elicits similar blood lactate concentrations during kayak ergometer and open water kayak training in both single and team boats. PMID- 11774064 TI - The effect of concurrent endurance and strength training on quantitative estimates of subsarcolemmal and intermyofibrillar mitochondria. AB - We examined the effect of combined strength and endurance training on quantitative estimates of mitochondria in subsarcolemmal and intermyofibrillar regions of muscle fibers. Ten subjects (five males, five females) participated in a 12 week program of combined strength and endurance training. Seven subjects (three males and four females) served as controls. Biopsy samples from the vastus lateralis were obtained before and after training in both groups and also at the mid-point of training in the exercise group. Measurement of succinate dehydrogenase activity throughout muscle fibers, as a quantitative estimate of mitochondrial subpopulations, revealed no differences between exercise and control groups before and after training. Within the exercise group, there was a significant increase in succinate dehydrogenase activity in all regions of muscle fibers from before to after training. There was also a significant increase in succinate dehydrogenase activity in the subsarcolemmal, relative to the intermyofibrillar region from mid-(six weeks) to after-training ( regional distribution x time; p < 0.05). This may have been associated with an oxidative shift in fiber types, as type I fiber percentage was increased in the exercise, compared to the control group (group x time; p < 0.05). We conclude that mitochondrial populations undergo differential changes throughout training. IMF mitochondria increase in a linear manner throughout training, while SS mitochondria undergo a preferential increase late in training. This increase late in training may be related to an increase in proportion of type I fibers. PMID- 11774065 TI - Running economy is negatively related to sit-and-reach test performance in international-standard distance runners. AB - The purpose of this study was to investigate the relationship between running economy (RE) and lower body flexibility. Thirty-four international-standard male distance runners (mean +/- s, age 27 +/- 5 years; body mass 64.9 +/- 4.2 kg; VO(2)max 72.8 +/- 3.7 ml x kg(-1) x min(-1)) gave written consent to participate in this study. The subjects performed an incremental treadmill test for the assessment of RE, lactate threshold and VO(2)max, and the sit-and-reach test was used to assess their general lower body and trunk flexibility. Running speeds below the lactate threshold were used to explore the relationship between running economy and sit-and-reach test performance. At 16.0 km x h(-1), the VO(2) was 50.6 +/- 3.7 ml x kg(-1) x min(-1) (range: 44.2 to 57.1 ml x kg(-1) x min(-1)). Pearson product moment correlation coefficients revealed no significant relationships between aerobic demand at 16.0 km x h(-1) and age (r = - 0.19), height (r = 0.15), body mass (r = - 0.18), or VO(2)max (r = - 0.004). However, there was a highly significant relationship between aerobic demand at 16.0 km x h(-1) and the sit-and-reach test score (r = 0.68; p < 0.0001). These results suggest that the least flexible runners are also the most economical. It is possible that stiffer musculotendinous structures reduce the aerobic demand of submaximal running by facilitating a greater elastic energy return during the shortening phase of the stretch-shortening cycle. PMID- 11774066 TI - Treadmill exercise negatively affects visual contribution to static postural stability. AB - This study was undertaken to explore the nature of impaired postural stability following physical exercise. Nine healthy subjects (aged 24 +/- 3 years) were subjected to 30 min of treadmill walking or running on two separate occasions. Walking and running speeds (1.9 to 2.2 m/s) were chosen to induce equal energy expenditure. During treadmill exercise, kinematic analysis of head movement was performed. Prior to and immediately following exercise, postural sway was evaluated as mean velocity of centre of pressure (VCOP), measured on a force plate during 30 s quiet stance with eyes open or eyes closed. The results indicate that exercise increased two-dimensional postural sway by 9 - 19 % in eyes open, but not in the eyes closed condition. The deteriorating effect of exercise was both evident in the sagittal and in the frontal plane, although the effect on the former was slightly more transient. Post-exercise sway values were significantly higher after running than after walking. Kinematic analysis of head movement confirmed larger vertical displacement and acceleration pattern in running compared to walking. It is concluded that exercise of moderate intensity deteriorates visual contribution to postural stability. The effect is evident as an initial destabilisation in the sagittal direction and a less transient loss of latero-lateral stability. Running tends to disturb postural stability more than walking, possibly due to more excessive head movement and disturbance of vestibular and visual information centres. PMID- 11774067 TI - Body composition and cardiorespiratory fitness indicators in prepubescent boys and girls. AB - Abstract. Relations between frequently used indicators of cardiorespiratory fitness, sex and body composition were studied in a birth-cohort based sample of young prepubescent children (age range: 6.8 - 8.2 years). The Bruce treadmill test was used to assess submaximal heart rate, endurance time (ET), calculated total work (W(total)) and maximal power output (P(max)) in 100 children (50 boys, 50 girls). Body composition was determined by skinfold measurements. In 17 children, maximal oxygen consumption was measured. Percent body fat was negatively associated with ET and relative oxygen uptake (ml x min(-1) x kg(-1)) and was positively related to submaximal heart rate at 6 minutes exercise (HR6). Fat-free mass was positively related to W(total), P(max) and absolute oxygen uptake (ml x min(-1)). Relative oxygen uptake (ml x min(-1) x kg(-1)) was related to ET. Absolute oxygen uptake (ml x min(-1)) was related to W(total) and P(max). The observed differences in indicators of cardiorespiratory fitness between boys and girls were largely attributable to a difference in body composition. The results further demonstrate that when oxygen uptake measurement is not feasible, W(total) or P(max) (expressed per kilogram fat-free mass) seem to provide better indicators of aerobic power than endurance time. PMID- 11774068 TI - Modelling the transfers of training effects on performance in elite triathletes. AB - This study investigated the effects of 40-weeks training in swimming, cycling and running on performances in swimming, running and triathlon competitions in four elite triathletes. The training stimulus was calculated using the exercise heart rate. The level of performance was measured in running by a submaximal 30 min run, in swimming by a 5 x 400 m all-out test and subjectively in triathlon competitions. A mathematical model using one to three first order transfer functions linked actual and modelled performances by minimizing the residual sum of squares between them. The relationships between training and performances were significant in running (tau(1) = 20; tau(2) = 10; r = 0.74; p < 0.001) and in swimming (tau(1) = 31; r = 0.37; p = 0.03), supporting the principle of specificity of the training loads. Cross-transfer training effects were identified between cycling and running (tau(1 = )42; r = 0.56; p < 0.001), but not with swimming performances. In addition, the training loads completed in running were shown to have a major effect on performances in triathlon competition (tau(1 = )52; tau(2 = )4; r = 0.52; p < 0.001), indicating that running training is an essential part of triathlon performance. Swimming appears to be a highly specific activity, which does not gain nor provide benefits from/to other activities (i. e. cycling and running). The present study shows that cross-transfer training effects occur between cycling training and running performance in elite triathletes. A similar cross-training effect does not seem to occur for swimming performance. PMID- 11774069 TI - Functional instability of the ankle: differences in patterns of ankle and knee movement prior to and post landing in a single leg jump. AB - The aim of this study was to investigate motor control in subjects with functional instability of the ankle joint. This was achieved by analysing patterns of lower extremity motion prior to and immediately following landing during single leg jumping in subjects with functional instability of the ankle. Fourteen subjects with unilateral functional instability and 10 healthy control subjects performed single leg jumps from a 40 cm height whilst angular displacement of their ankle and knee joints were recorded. Subjects with functional instability demonstrated significantly greater ankle dorsiflexion over the period encompassing 10 ms pre landing to 20 ms post landing (p < 0.05). They also exhibited a significantly greater level of knee flexion than controls over the period from 20 ms pre landing to 60 ms post landing (p < 0.05). The timing of these significant differences leads us to conclude that they do not arise as a result of reflexively mediated peripheral events following landing. PMID- 11774070 TI - Change in salivary IgA following a competitive marathon race. AB - The influence of carbohydrate (1 l/h of a 6 % carbohydrate beverage), gender, and age on salivary IgA (sIgA) changes and incidence of upper respiratory tract infection (URTI) was studied in 98 runners following two competitive marathon races. The pattern of change in sIgA concentration differed significantly between carbohydrate (C) (N = 48) and placebo (P) (N = 50) groups, with higher post-race values measured in P. However, when this was adjusted for saliva protein concentration and saliva secretion rate, no difference between groups was measured. For all subjects combined, sIgA concentration, saliva IgA: protein ratio (spIgA), and sIgA secretion rates fell significantly (21 %, 31 %, and 25 %, respectively) below pre-race levels by 1,5-h post-race (p < 0.001). The pattern of change in all saliva measures did not differ significantly between the 12 women and 86 men in this study, and between the 23 older (> or =50 yr) and 75 younger (< 50 yr) subjects. Ninety-three subjects returned health/sickness logs, and of these, 16 (17 %) reported developing URTI during the 15-d period following the race event. The 1.5-h post-race spIgA concentration, but not sIgA concentration or secretion rate, was lower in runners reporting URTI compared to those who did not (254 +/- 30 and 388 +/- 26 microg*g(-1), respectively, p = 0.002), and this was negatively correlated with the post-race plasma cortisol concentration (r = -0.36, p < 0.001). Of the 16 runners, six were in the C group and 10 in the P group (Chi square = 1.11, p = 0.293). In conclusion, the output of sIgA decreased in runners following a competitive marathon, and this was not influenced by carbohydrate ingestion, age, or gender. PMID- 11774071 TI - Gdnf haploinsufficiency causes Hirschsprung-like intestinal obstruction and early onset lethality in mice. AB - Hirschsprung disease (HSCR) is a common congenital disorder that results in intestinal obstruction and lethality, as a result of defective innervation of the gastrointestinal (GI) tract. Despite its congenital origin, the molecular etiology of HSCR remains elusive for >70% of patients. Although mutations in the c-RET receptor gene are frequently detected in patients with HSCR, mutations in the gene encoding its ligand (glial cell line-derived neurotrophic factor [GDNF]), are rarely found. In an effort to establish a possible link between human HSCR and mutations affecting the Gdnf locus, we studied a large population of mice heterozygous for a Gdnf null mutation. This Gdnf(+/-) mutant cohort recapitulates complex features characteristic of HSCR, including dominant inheritance, incomplete penetrance, and variable severity of symptoms. The lack of one functioning Gdnf allele causes a spectrum of defects in gastrointestinal motility and predisposes the mutant mice to HSCR-like phenotypes. As many as one in five Gdnf(+/-) mutant mice die shortly after birth. Using a transgenic marking strategy, we identified hypoganglionosis of the gastrointestinal tract as a developmental defect that renders the mutant mice susceptible to clinical symptoms of HSCR. Our findings offer a plausible way to link an array of seemingly disparate features characteristic of a complex disease to a much more narrowly defined genetic cause. These findings may have general implications for the genetic analysis of cause and effect in complex human diseases. PMID- 11774072 TI - Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. AB - "Early-onset glaucoma" refers to genetically heterogeneous conditions for which glaucoma manifests at age 5-40 years and for which only a small subset is molecularly characterized. We studied the role of MYOC, CYP1B1, and PITX2 in a population (n=60) affected with juvenile or early-onset glaucoma from the greater Toronto area. By a combination of single-strand conformation polymorphism and direct cycle sequencing, MYOC mutations were detected in 8 (13.3%) of the 60 individuals, CYP1B1 mutations were detected in 3 (5%) of the 60 individuals, and no PITX2 mutations were detected. The range of phenotypic expression associated with MYOC and CYP1B1 mutations was greater than expected. MYOC mutations included cases of juvenile glaucoma with or without pigmentary glaucoma and mixed mechanism glaucoma. CYP1B1 mutations involved cases of juvenile open-angle glaucoma, as well as cases of congenital glaucoma. The study of a family with autosomal dominant glaucoma showed the segregation of both MYOC and CYP1B1 mutations with disease; however, in this family, the mean age at onset of carriers of the MYOC mutation alone was 51 years (range 48-64 years), whereas carriers of both the MYOC and CYP1B1 mutations had an average age at onset of 27 years (range 23-38 years) (P=.001). This work emphasizes the genetic heterogeneity of juvenile glaucoma and suggests, for the first time, that (1) congenital glaucoma and juvenile glaucoma are allelic variants and (2) the spectrum of expression of MYOC and CYP1B1 mutations is greater than expected. We also propose that CYP1B1 may act as a modifier of MYOC expression and that these two genes may interact through a common pathway. PMID- 11774073 TI - A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13. AB - The hereditary spastic ataxias (HSA) are a group of clinically heterogeneous neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia. HSA was diagnosed in three unrelated autosomal dominant families from Newfoundland, who presented mainly with severe leg spasticity, dysarthria, dysphagia, and ocular-movement abnormalities. A genomewide scan was performed on one family, and linkage to a novel locus for HSA on chromosome 12p13, which contains the as-yet-unidentified gene locus SAX1, was identified. Fine mapping confirmed linkage in the two large families, and the third, smaller family showed LOD scores suggestive of linkage. Haplotype construction by use of 13 polymorphic markers revealed that all three families share a disease haplotype, which key recombinants and overlapping haplotypes refine to about 5 cM, flanked by markers D12S93 and GATA151H05. SAX1 is the first locus mapped for autosomal dominant HSA. PMID- 11774074 TI - A genomewide linkage screen for relative hand skill in sibling pairs. AB - Genomewide quantitative-trait locus (QTL) linkage analysis was performed using a continuous measure of relative hand skill (PegQ) in a sample of 195 reading disabled sibling pairs from the United Kingdom. This was the first genomewide screen for any measure related to handedness. The mean PegQ in the sample was equivalent to that of normative data, and PegQ was not correlated with tests of reading ability (correlations between minus sign0.13 and 0.05). Relative hand skill could therefore be considered normal within the sample. A QTL on chromosome 2p11.2-12 yielded strong evidence for linkage to PegQ (empirical P=.00007), and another suggestive QTL on 17p11-q23 was also identified (empirical P=.002). The 2p11.2-12 locus was further analyzed in an independent sample of 143 reading disabled sibling pairs, and this analysis yielded an empirical P=.13. Relative hand skill therefore is probably a complex multifactorial phenotype with a heterogeneous background, but nevertheless is amenable to QTL-based gene-mapping approaches. PMID- 11774075 TI - Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome. AB - To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups. PMID- 11774076 TI - Postoperative bacteremia secondary to surgical site infection. AB - We evaluated all surgical site infections (SSI) and postoperative bacteremias secondary to SSI as part of an ongoing active surgical surveillance program at a community hospital. Among 40,191 surgical procedures, we identified 515 patients with SSI and 47 with postoperative bacteremia secondary to SSI. Four variables were examined as potential predictors for developing postoperative bacteremia secondary to an SSI: National Nosocomial Infections Surveillance risk index, abdominal surgery, surgical procedures with an implantable device, and the presence of Staphylococcus aureus in wounds. Of these 4 variables, only one, S. aureus isolated from a wound culture, was associated with an increased risk of developing postoperative bacteremia secondary to SSI. Patients with S. aureus isolated in either pure or mixed culture from SSI were more than twice as likely to have postoperative bacteremia secondary to SSI than were those without S. aureus wound infection. PMID- 11774077 TI - Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. AB - Human herpesvirus 6 (HHV-6) appears to cause central nervous system (CNS) syndromes, especially in hematopoietic stem cell transplant (HSCT) recipients. We reviewed our experience with HHV-6-associated CNS disease to evaluate both the clinical and virological presentation and response to antiviral therapy. A search of our virology database from January 1998 through June 2000 identified 11 HSCT recipients who had HHV-6 DNA detected by polymerase chain reaction in cerebrospinal fluid (CSF); 8 of whom had CNS dysfunction without another clear etiology identified. HHV-6 levels in serum and CSF were evaluated before and after ganciclovir and/or foscarnet therapy. Median log HHV-6 CSF levels appeared to decrease over time concurrent with antiviral therapy (serum level, 2.0 vs. 0 copies/mL [P=.38]; CSF level, 4.4 vs. 2.0 copies/mL [P=.13], sign test). Our data suggests that HHV-6 may cause moderate to severe CNS disease after HSC transplantation. Prospective studies are needed to define the spectrum of HHV-6 associated disease and to determine whether antiviral therapy offers clinical benefit. PMID- 11774078 TI - Use of indicators to evaluate the quality of community-acquired pneumonia management. AB - Quality-assessment indicators for community-acquired pneumonia (CAP) founded on health care structure, process, and outcome have been recommended as a potential audit tool to evaluate the delivery of care. We prospectively audited the treatment of 205 patients admitted with CAP to 2 hospitals in Dundee against some of these key standards. Patients with severe CAP were more likely to die (mortality rate, 42% versus 7%) and to receive antibiotics by the intravenous route (relative risk [RR], 1.81; 95% confidence interval [CI], 1.38-2.37) and within 4 hours of admission to the hospital (RR, 1.22; 95% CI, 0.92-1.62). There was a lack of uniformity regarding the amount of oxygen prescribed, with evidence of poor case record and drug prescription chart documentation related to oxygen therapy. Adherence to the recommended antibiotic policy was associated with reduced risk of death or readmission to the hospital (RR, 0.58; 95% CI, 0.34 1.00). However, in a multivariate analysis, severity of pneumonia was the strongest predictor of death or readmission (P=.004), and adherence to the antibiotic policy was not statistically significant (P=.154). Our study has confirmed the value of quality indicators in evaluating our CAP management and has stimulated the development and implementation of a local hospital-based integrated care pathway. PMID- 11774079 TI - Trends in multidrug-resistant Mycobacterium tuberculosis in relation to sputum smear positivity in Hong Kong, 1989-1999. AB - We studied retrospectively the territory-wide occurrence and trends of multidrug resistant tuberculosis (MDR-TB) in Hong Kong over an 11-year period during which a short-course directly observed therapy ("DOTS-Plus") strategy has been in operation. The overall MDR rate was 2.1% (primary, 1.4% and acquired, 9.5%) and declined at 0.08% per year: smear-positive primary MDR cases declined at yearly rate of -0.065% (R2=.23), and smear-negative primary MDR cases increased at 0.035% yearly. With declining rates of smear positivity, sputum culture has become the mainstay of detection of MDR-TB. Although the overall notification rates showed the elderly (age >65 years) age group to be most affected, the occurrence of MDR-TB has been consistently highest in the 35-65 year age group (60.4% of MDR caseload). We demonstrated declining rates of sputum smear positivity of MDR-TB in a DOTS-plus environment and that a centralized laboratory database is essential in gathering epidemiological information for identifying particular risk groups and monitoring trends of MDR-TB in a community. PMID- 11774080 TI - The molecular epidemiology of penicillin-resistant Streptococcus pneumoniae in the United States, 1994-2000. AB - The genetic relatedness of 672 penicillin-resistant isolates of Streptococcus pneumoniae (PRSP) recovered during national surveillance studies conducted in the United States during the periods of 1994-1995, 1997-1998, and 1999-2000 was determined by use of pulsed-field gel electrophoresis (PFGE). Overall, 104 different PFGE types were elucidated. For all study periods combined, the 12 most prevalent PFGE types included >75% of all isolates, and 5 types were closely related to widespread clones (Spain(23F)-1, France(9V)-3, Spain(6B)-2, Tennessee(23F)-4, and Taiwan(19F)-14). From 1994-1995 to 1999-2000, 3 major PFGE types (not closely related to 16 recognized clones) increased in prevalence. Multidrug resistance was identified among 96%-100% of the isolates in 9 of 12 predominant PFGE types. The prevalence of erythromycin resistance increased within 4 major PFGE types. These observations support the hypothesis that the dominant factor in the emergence of PRSP in the United States during the 1990s has been human-to-human spread of relatively few clonal groups that harbor resistance determinants to multiple classes of antibiotics. PMID- 11774082 TI - Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. AB - A total of 271 patients were prospectively followed up to determine whether patients whose hospital stay is complicated by diarrhea due to Clostridium difficile experience differences in cost and length of stay and survival rates when compared with patients whose stay is not complicated by C. difficile associated diarrhea. Forty patients (15%) developed nosocomial C. difficile associated diarrhea. These patients incurred adjusted hospital costs of $3669- that is, 54% (95% confidence interval [CI], 17%-103%)--higher than patients whose course was not complicated by C. difficile-associated diarrhea. The extra length of stay attributable to C. difficile-associated diarrhea was 3.6 days (95% CI, 1.5-6.2). C. difficile-associated diarrhea was not associated with excess 3-month or 1-year mortality after adjustment for age, comorbidity, and disease severity. On the basis of the findings of this study, a conservative estimate of the cost of this disease in the United States exceeds $1.1 billion per year. PMID- 11774081 TI - Risk factors for imipenem-resistant Pseudomonas aeruginosa among hospitalized patients. AB - Risk factors for the nosocomial recovery of imipenem-resistant Pseudomonas aeruginosa (IRPA) were determined. A case-control study design was used for the comparison of 2 groups of case patients with control patients. The first group of case patients had nosocomial isolation of IRPA, and the second group had imipenem susceptible P. aeruginosa (ISPA). Control patients were selected from the same medical or surgical services from which case patients were receiving care when isolation of IRPA occurred. Risk factors analyzed included antimicrobials used, comorbid conditions, and demographic variables. IRPA was recovered from 120 patients, and ISPA from 662 patients. Imipenem (odds ratio [OR], 4.96), piperacillin-tazobactam (OR, 2.39), vancomycin (OR, 1.80), and aminoglycosides (OR, 2.19) were associated with isolation of IRPA. Vancomycin (OR, 1.64), ampicillin-sulbactam (OR, 2.00), and second-generation cephalosporins (OR, 2.00) were associated with isolation of ISPA. Antibiotics associated with ISPA are different from antibiotics associated with IRPA. The OR for imipenem as a risk factor for IRPA is less than that reported from studies in which control group selection was suboptimal. PMID- 11774083 TI - Water disinfection for international and wilderness travelers. AB - Acquisition of waterborne disease is a substantial risk for international travelers to countries with inadequate sanitation facilities. It also poses smaller but still significant risks for wilderness travelers who rely on surface water in developed countries with low rates of diarrheal illness, such as the United States. This article reviews the etiology and risks associated with waterborne disease that might be encountered by both types of travelers. It also summarizes--and makes recommendations for--the various water-treatment methods available to travelers for reducing their risk of contracting waterborne disease. PMID- 11774084 TI - Evolution and current use of the tuberculin test. AB - Since it was first introduced in the late 1800s, the tuberculin test has undergone continual refinement in its formulation, standardization, and dosage, as well as its interpretation and indications for use. New guidelines have replaced universal screening with targeted testing and rigid definitions of positivity with individualized criteria formulated from a Bayesian approach. This review summarizes the evolution of the test and provides information to help gauge its predictive value. PMID- 11774085 TI - Azithromycin prophylaxis for Mycobacterium avium complex during the era of highly active antiretroviral therapy: evaluation of a provincial program. AB - Mycobacterium avium complex (MAC) disease was evaluated in a provincial program of azithromycin prophylaxis. Highly active antiretroviral therapy (HAART) was prescribed to 383 (65%) of 587 patients eligible for MAC prophylaxis (CD4 <75 cells/mm3). By use of an intent-to-treat analysis, MAC disease was observed in 21 of 271 patients who did not receive prophylaxis (incidence rate, 8 events per 100 person-years). MAC events occurred in 10 of 316 patients who received azithromycin (2.37 events per 100 person-years). Localized lymphadenitis compatible with immune reconstitution disease accounted for 23% of all MAC events, in contrast to studies in the pre-HAART era, where almost all cases were disseminated. None of the MAC isolates from the 10 prophylaxis failures were resistant to azithromycin. Azithromycin appeared to be protective against disseminated MAC in patients who were either unresponsive or nonadherent to HAART, but it did not prevent the development of immune reconstitution disease due to MAC. PMID- 11774086 TI - Influence of human immunodeficiency virus type 1 infection on acute hepatitis A virus infection. AB - To assess the possible influence of human immunodeficiency virus type 1 (HIV-1) infection on the clinical course of acute hepatitis A virus (HAV) infection, 15 HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients (P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days). HIV-1-infected patients had lower elevations in alanine aminotransferase levels than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline phosphatase levels than did non-HIV-infected patients (P<.001). Some HIV-1 infected patients still had HAV viremia when clinical symptoms had disappeared and alanine aminotransferase levels had returned to normal (60-90 days after the onset of symptoms). HIV-1 infection was associated with prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV infection in HIV-1 infected homosexual men. PMID- 11774087 TI - Reduction of abdominal obesity in lipodystrophy associated with human immunodeficiency virus infection by means of diet and exercise: case report and proof of principle. AB - Lipodystrophy associated with human immunodeficiency virus infection causes abdominal fat gain, peripheral subcutaneous fat atrophy, insulin resistance, low levels of high-density lipoprotein cholesterol, and hypertriglyceridemia. An exercise program combined with a moderate-fat, low-glycemic-index, high-fiber diet can reverse several aspects of lipodystrophy, and, until specific treatment is available, should be considered for treatment of lipodystrophy. PMID- 11774088 TI - Pulmonary candidiasis in patients with cancer: an autopsy study. AB - For patients who had cancer and autopsy-proven pneumonia, we evaluated whether cultures of respiratory secretions (sputum and/or bronchoalveolar lavage) performed < or =4 weeks before autopsy were a reliable basis for the diagnosis of pulmonary candidiasis. Pulmonary candidiasis was identified at autopsy in 36 patients, but common clinical predictors were insensitive for this diagnosis. For sputum culture, the sensitivity, specificity, and the positive and negative predictive values were 85%, 60%, 42%, and 93%, respectively; for bronchoalveolar lavage culture, these values were 71%, 57%, 29%, and 89%, respectively. PMID- 11774089 TI - Use of rabies vaccines after reconstitution and storage. AB - Storing freshly reconstituted purified chick embryo rabies vaccine at 4 degrees C for 1 week allowed use of <1 ampoule of 1.0 mL for 1 patient for day 0, 3, and 7 immunizations, representing considerable savings in vaccine and also possibly allowing use of this cost-saving regimen in centers that see <1 rabies-exposed patient daily. The 90-day booster dose mandated in the current intradermal regimen may not be necessary if the day 28 dose is doubled, eliminating 1 clinic visit at no additional cost in vaccine. PMID- 11774090 TI - Infection with non-B subtype HIV type 1 complicates management of established infection in adult patients and diagnosis of infection in newborn infants. PMID- 11774091 TI - Severe ototoxicity in a health care worker who received postexposure prophylaxis with stavudine, lamivudine, and nevirapine after occupational exposure to HIV. PMID- 11774092 TI - Safety of outpatient parenteral antimicrobial therapy for endocarditis. PMID- 11774093 TI - Business aspects of infectious diseases. PMID- 11774094 TI - The United States Food and Drug Administration and the end of antibiotics. PMID- 11774095 TI - Leptin and renal disease. AB - Leptin is a small peptide hormone that is mainly, but not exclusively, produced in adipose tissue. The circulating leptin concentration therefore directly reflects the amount of body fat. Leptin was identified through positional cloning of the obese (ob) gene, which is mutated in the massively obese ob/ob mouse, and it has a pivotal role in regulating food intake and energy expenditure. It binds to the so-called long receptor (Ob-Rb) in the hypothalamus and regulates food intake through the release of other neurotransmitters. Moreover, leptin exerts several other important metabolic effects on peripheral tissue, including modification of insulin action, induction of angiogenesis, and modulation of the immune system. As a small peptide, leptin is cleared principally by the kidney. Not surprisingly, serum leptin concentrations are increased in patients with chronic renal failure and those undergoing maintenance dialysis. Whether the hyperleptinemia of chronic renal failure contributes to some uremic manifestations, such as anorexia and weight loss, requires additional investigation. The kidney expresses abundant concentrations of the truncated isoform of the leptin receptor Ob-Ra, but only a small amount of the full-length receptor Ob-Rb. We recently discovered that leptin has direct effects on renal pathophysiological characteristics. Both cultured glomerular endothelial cells and mesangial cells obtained from the diabetic db/db mouse possess the Ob-Ra receptor, but whether biological effects of leptin are transduced through this receptor remains unknown. In glomerular endothelial cells, leptin stimulates cellular proliferation, transforming growth factor-beta1 (TGF-beta1) synthesis, and type IV collagen production. Conversely, in mesangial cells, leptin upregulates synthesis of the TGF-beta type II receptor, but not TGF-beta1, and stimulates glucose transport and type I collagen production through signal transduction pathways involving phosphatidylinositol-3-kinase. These data suggest that leptin triggers a paracrine interaction in which glomerular endothelial cells secrete TGF-beta, to which sensitized mesangial cells may respond. Both cell types increase their expression of extracellular matrix in response to leptin. Infusion of leptin into normal rats for 3 weeks fosters the development of focal glomerulosclerosis and proteinuria. Additional previously described direct and indirect effects of leptin on the kidney include natriuresis, increased sympathetic nervous activity, and stimulation of reactive oxygen species. These findings collectively suggest that the kidney is not only a site of leptin metabolism, but also a target organ for leptin action in pathophysiological states. PMID- 11774096 TI - Renal manifestations of congenital lactic acidosis. AB - Congenital lactic acidoses (CLAs) constitute a group of rare inborn errors of mitochondrial metabolism in which cellular energy failure is the defining biochemical abnormality. We report the principal manifestations of renal dysfunction in 35 children with CLA caused by defects in either the pyruvate dehydrogenase multienzyme complex or one or more components of the respiratory chain. The most prominent renal abnormalities included bicarbonaturia, phosphaturia, hypercalciuria, complete Fanconi's syndrome, proteinuria, and decreased glomerular filtration rate. These data were compared with those from 79 previously published cases. Clinical manifestations of renal dysfunction in CLA are common and may be the first presenting sign of the disease. The glomerulus and proximal renal tubule appear to be the anatomic sites most vulnerable to abnormal mitochondrial energy transduction. We propose that the primary defect in mitochondrial energy metabolism, together with the consequent intracellular accumulation of lactate and hydrogen ions, precipitates a state of tissue injury that, unless interrupted, becomes self-perpetuating and ultimately leads to renal cell death. PMID- 11774097 TI - Factor H-related protein-5: a novel component of human glomerular immune deposits. AB - Factor H-related protein-5 (FHR-5) is a newly described human plasma protein with structural similarities to human factor H and the four other recently described factor H-related proteins. Unlike the other factor H-related proteins, FHR-5 was initially identified at the protein, rather than complementary DNA, level in studies of glomerular immune deposit composition. To determine the incidence and pattern of detection of FHR-5 in human renal biopsy specimens, a prospective study of 100 consecutive biopsies was performed using anti-FHR-5 monoclonal antibody and indirect immunofluorescence. The pattern of FHR-5 deposition is very similar to that of other complement components, C3 and SC5b-9. It is detected in all complement-containing glomerular immune deposits and has a pattern of extraglomerular deposition similar to that of other complement components. This study shows FHR-5 to be strongly associated with glomerular complement deposition and suggests a role in complement activation or regulation. It may be an important mediator of glomerular disease. PMID- 11774098 TI - Predictive value of initial histology and effect of plasmapheresis on long-term prognosis of rapidly progressive glomerulonephritis. AB - Intensive immunosuppressive therapy has improved the outcome of patients with rapidly progressive glomerulonephritis (RPGN), which progresses to end-stage renal failure in 90% of patients without intervention. However, it remains unclear which patients benefit most from immunosuppressive therapy and whether plasmapheresis improves long-term outcome. This prospective multicenter study randomized 39 patients with biopsy-proven RPGN (Couser type II, n = 6; pauci immune type III, n = 33) to undergo either immunosuppressive therapy with prednisone and cyclophosphamide (n = 18) or plasmapheresis in addition to immunosuppression (n = 21). Patients were observed for a mean of 127 months or until reaching the end points of hemodialysis or death. Six of 11 patients who were initially dialysis dependent recovered renal function; however, 2 of those patients required dialysis therapy again after 10 and 105 months. Overall, 15 of 39 patients reached end-stage renal failure after a mean of 25 months, and 4 patients died before requiring hemodialysis therapy. Plasmapheresis had no significant effect on renal or patient survival in type II or pauci-immune (type III) RPGN, independently of age, sex, or serum creatinine level at the time of diagnosis. Overall, probabilities of dialysis-free survival were 0.80, 0.67, 0.55, and 0.48 after 12, 24, 60, and 120 months, respectively. Histological characteristics at the time of diagnosis predicted the effect of immunosuppression on renal outcome. All patients were dialysis dependent within 24 months if more than one third of glomeruli were totally sclerosed on the initial histological examination. Interstitial fibrosis also correlated significantly with the risk for progression to renal failure. Conversely, long term dialysis-free survival was significantly more likely in patients with a greater number of crescents than in those with a low number of crescents. In conclusion, plasmapheresis does not add to the improvement in outcome reached by immunosuppression alone. Crescents on initial histological examination correlate with a favorable outcome. However, 90% of patients who initially have glomerular sclerosis present become dialysis dependent. Overall, approximately 50% of patients are alive and off dialysis therapy 10 years after the diagnosis of type II or type III RPGN using immunosuppression with cyclophosphamide and prednisone. PMID- 11774099 TI - Association of the uteroglobin gene polymorphism with IgA nephropathy. AB - Immunoglobulin A (IgA) nephropathy results from the abnormal deposition of IgA in the renal mesangium. Genetic factors may be involved in the development and progression of IgA nephropathy. Uteroglobin (UG) is a steroid-inducible, cytokine like, multifunctional protein with anti-inflammatory and immunomodulatory properties. The knockout or antisense mouse of the UG gene develops renal disease similar to IgA nephropathy. We analyzed the UG gene as a candidate for a predisposing factor in 61 Japanese patients with IgA nephropathy (23 children, 38 adults) and detected only the G38A mutation. The gene frequency of the G38A mutation in patients was 0.43, not significantly different from the frequency of 0.36 in healthy controls. However, the frequency of patients homozygous for G38A was twice that of controls, and a significant increase was seen in child patients. We measured serum UG levels in patients and healthy adults. A significant decrease in serum UG levels in homozygotes of G38A compared with homozygotes of G38 was detected only in adult women patients and controls. There is no information on where serum UG is produced or how UG may work in association with IgA nephropathy. However, it is possible that the effect of G38A may be apparent under such stimulation as sex steroids or infections, and homozygotes of the G38A mutation cannot produce sufficient UG in response to stimulation and may be predisposed to IgA nephropathy, especially in childhood. PMID- 11774100 TI - Pulmonary renal syndrome: a 4-year, single-center experience. AB - Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS. PMID- 11774101 TI - Capecitabine in the treatment of metastatic renal cell carcinoma failing immunotherapy. AB - Capecitabine is a novel fluoropyrimidine carbamate, orally administered and selectively activated to fluorouracil by a sequential triple-enzyme pathway in liver and tumor cells. This prospective trial aims to evaluate the therapeutic effects and systemic toxicities of capecitabine in patients with metastatic renal cell carcinoma in which immunotherapy failed. Twenty-six patients (median age, 58 years; range, 47 to 76 years) with disease in which first- or second-line immunotherapy treatment failed entered the trial. Median time of observation was 13+ months (range, 3 to 25+ months). Capecitabine was administered in the outpatient setting orally at a dose of 2,500 mg/m2/d divided into two daily doses for 14 days, followed by 7 days of rest. This schedule was repeated in 3-week intervals. Twenty-six patients are now assessable for toxicity, and 23 patients, for response. We observed a partial response to treatment in 2 patients (8.7%), minor response in 5 patients (21.7%), stable disease in 13 patients (56.5%), and continued disease progression despite treatment in only 3 patients (13.1%). Outpatient capecitabine therapy was well tolerated, and World Health Organization (WHO) grade III toxicity in these 26 patients consisted of hand-foot syndrome in 2 patients (7.7%) and anemia in 1 patient (3.8%). We did not observe WHO grade IV toxicity. Oral capecitabine appears to be a promising treatment with a favorable toxicity profile in patients with advanced renal cell carcinoma and should be evaluated in first- and second-line treatment schedules as monotherapy, as well as in combination with immunotherapy agents. PMID- 11774102 TI - Failure of continuous venovenous hemofiltration to prevent death in paraquat poisoning. AB - Paraquat poisoning is characterized by multiorgan failure and pulmonary fibrosis with respiratory failure. Multiorgan failure with circulatory collapse is a major cause of early death within 3 days of paraquat ingestion. Recent studies suggested that continuous venovenous hemofiltration (CVVH) had a role in the treatment of multiorgan failure by promoting hemodynamic stability. We therefore evaluated the effect of prophylactic CVVH in 80 patients with paraquat poisoning (August 1996 to February 1999). The amount ingested was 2.1 +/- 1.0 mouthfuls (as 20% concentrate). All patients were treated with hemoperfusion (HP; duration, 6.4 +/- 3.0 hours) within 24 hours of ingestion and then randomly assigned to the HP alone or HP-CVVH group. Forty-four patients underwent HP only, and 36 patients underwent CVVH (duration, 57.4 +/- 31.3 hours; ultrafiltration volume, 40.2 +/- 4.8 L/d) after HP. Although time to death after ingestion was significantly longer in the HP-CVVH than HP group (5.0 +/- 5.0 versus 2.5 +/- 2.1 days; P < 0.05), there was no difference in mortality rates between the two groups (66.7% versus 63.6%; P = 0.82). In the HP group, early circulatory collapse was a major cause of death compared with the HP-CVVH group, in which late respiratory failure was a major cause of death. In conclusion, prophylactic CVVH after HP prevented early death caused by circulatory collapse and prolonged survival time. However, it could not prevent late death caused by respiratory failure and did not provide a survival benefit in acute paraquat poisoning. PMID- 11774103 TI - Rapid decline in renal function reflects reversibility and predicts the outcome after angioplasty in renal artery stenosis. AB - Percutaneous transluminal renal angioplasty (PTRA) has a beneficial effect on renal function in some, but not all, patients with atheromatous renal artery stenosis. Our aim is to identify factors influencing clinical success after PTRA in this group of patients. Seventy-three patients undergoing PTRA were studied; 14 patients were excluded from final analysis because of restenosis. All patients had chronic renal failure secondary to vascular nephropathy and renal artery stenosis. The diagnosis of renal artery stenosis was based on carbon dioxide digital angiography showing greater than 60% luminal narrowing. The rate of renal failure progression was assessed by the slope of the regression line of serum creatinine versus time. At least three consecutive creatinine measurements before and after angioplasty were required for study entry. Response to PTRA was made by comparison of the slope before and after PTRA. The association of age, serum creatinine level, proteinuria, renal size, pre-PTRA slope value, diabetes, ischemic heart disease, peripheral vascular disease, and cerebrovascular disease with response to PTRA was assessed by multiple regression analysis, with changes in slope values as the dependent variable. Renal function improved in 34 of 59 patients (57.6%). Mean follow-up was 627 +/- 284 (SD) days. The slope of the reciprocal serum creatinine plot before PTRA was significantly associated with a favorable change in progression rate after PTRA (beta = -0.012; P = 0.004). A scatter plot showed a statistically significant inverse correlation between pre PTRA slope values and post-PTRA slope changes (r = -0.46; P = 0.000). Rapidly progressive renal failure is associated with a favorable response on renal failure progression after PTRA in patients with vascular nephropathy and renal artery stenosis. PMID- 11774104 TI - Fluvastatin improves lipid abnormalities in patients with moderate to advanced chronic renal insufficiency. AB - Chronic renal insufficiency is characterized by specific abnormalities in lipoprotein metabolism, affecting both apolipoprotein A (apo A)- and apo B containing lipoproteins. To evaluate the effects of fluvastatin, a synthetic 3 hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on renal dyslipoproteinemia, we performed a randomized, double-blind, placebo-controlled, two-way, period cross-over study. Study patients were administered fluvastatin, 40 mg/d, or placebo during 8 weeks in randomized order. Forty-five nonnephrotic patients (28 men, 17 women) without diabetes with moderate to advanced chronic renal insufficiency participated in the study. Their mean age was 56.4 +/- 11.0 years. Glomerular filtration rate ranged from 12 to 44 mL/min/1.73 m2 of body surface area (mean, 27.5 +/- 10.5 mL/min/1.73 m2). Fluvastatin treatment resulted in significant reductions in the primary outcome variables low-density lipoprotein cholesterol (LDL-C; -26%; P < 0.001), apo B (-21%; P < 0.001), and lipoprotein B complex (Lp-Bc) (-14%; P < 0.01). There were statistically significant differences between fluvastatin and placebo treatment for the secondary outcome variables total cholesterol (-19%), triglycerides (TGs; -13%), VLDL-C (-13%), apo E (-13%), and Lp-B (-22%). There was no treatment effect on high-density lipoprotein cholesterol or lipoprotein(a). Fluvastatin treatment was well tolerated, with no serious adverse events during the study. In conclusion, fluvastatin treatment was well tolerated in patients with moderately advanced renal insufficiency and led to a significant reduction in cholesterol-rich, but to a lesser extent in TG-rich, apo B-containing lipoproteins. It remains to be clarified whether these positive changes in lipoprotein profile also will result in attenuation of the atherosclerotic process in these patients, as well as beneficially affect the progression of chronic renal failure. PMID- 11774105 TI - Clinical and demographic predictors of exercise capacity in end-stage renal disease. AB - Patients on maintenance hemodialysis therapy for end-stage renal disease have reduced exercise tolerance. Multiple processes related to uremia and hemodialysis have been implicated in the pathophysiology of this impairment. However, limited data are available to identify the separate and combined effects of clinical factors on the degree of impairment for individuals within this population. For this purpose, data from 193 patients who had undergone exercise testing for two clinical trials were retrospectively analyzed. Univariate and multiple linear regression analyses were used to identify demographic and clinical correlates of peak exercise oxygen uptake (VO2). Peak VO2 averaged 18.5 +/- 6.4 mL/min/kg. On univariate analysis, peak VO2 correlated positively with male sex and hemoglobin, serum albumin, and serum creatinine concentrations and correlated negatively with dialytic age and diagnosis of diabetes or chronic heart failure. In a multiple linear regression model, sex, hemoglobin concentration, age, and diagnosis of diabetes each remained statistically significant. Together, factors included in the model accounted for 41% of the variability in peak VO2 (P = 0.0001). Among factors not correlating significantly with peak VO2 were resting blood pressure, serum carnitine level, and urea clearance assessed by Kt/V. Findings show the range of exercise impairment among clinically stable ambulatory hemodialysis patients, which may be sufficient to interfere with normal daily activities for many of these patients. Although this impairment may be broadly attributable to physiological consequences of uremia, the degree of impairment for individual patients is predicted by demographic factors, coexistent disease, and factors potentially modified by medical therapeutics. PMID- 11774106 TI - A longitudinal study of the repeated use of alteplase as therapy for tunneled hemodialysis catheter dysfunction. AB - When hemodialysis catheters allow only poor or no blood flow, it has become established practice in many centers to instill a thrombolytic agent in an attempt to clear the catheter. The catheter survival advantage gained by repeated use of such treatment is not known. In a prospective study, we analyzed all uses of alteplase in the setting of inadequate catheter blood flow in a cohort of 570 catheters over a 2(1/2)-year period. The time from alteplase instillation to the next episode in which it was required or catheter removal for nonfunction or thrombosis was recorded. Survival analysis was used to estimate the additional catheter survival afforded by each treatment. After censoring for elective catheter removal, the overall catheter half-life was 10.2 months. Catheter malfunction or thrombosis was the most common indication for catheter removal (36.3% of all catheters removed). Alteplase instillation was necessary in 2.77% of dialysis sessions. The median time from the first to second treatment or catheter removal for nonfunction or thrombosis was 27 days (95% confidence interval, 15.7 to 32.3). Additional median survival advantage gained from each subsequent treatment ranged from 10 to 18 days. Treatment of recurrent catheter malfunction with alteplase allows for a median of only five to seven additional dialysis sessions before the treatment must be repeated or the catheter must be exchanged. Although associated with minimal disruption to the dialysis schedule, the ultimate clinical benefit and cost-effectiveness of such treatment is doubtful. PMID- 11774107 TI - Hemodialysis vascular access survival: upper-arm native arteriovenous fistula. AB - Achieving Dialysis Outcomes Quality Initiative guidelines for native arteriovenous fistulae using the radiocephalic forearm fistula (lower-arm fistula [LAF]) is difficult. This study reports results using the upper-arm native arteriovenous fistula (UAF). From a prospective access database (1992 to 1998), this study was based on 204 patients (322 accesses). Average patient age was 56 +/- 1 years, 63% were men, and 47% had diabetes. A native fistula was the first access in 73% of patients (36%, LAFs; 37%, UAFs) and accounted for 48% of subsequent accesses (13%, LAFs; 35%, UAFs). Younger men were more likely to receive an LAF, but there was no demographic difference between patients receiving a UAF or arteriovenous graft (AVG). Both primary unassisted and cumulative access patencies were significantly better for UAFs than either LAFs or AVGs. For first accesses, cumulative access patency rates at 1, 3, and 5 years were 71%, 57%, and 57% for UAFs; 54%, 46%, and 36% for LAFs; and 54%, 28%, and 0% for AVGs (P < 0.01). Despite shorter access survival, AVGs required more total access procedures than either UAFs or LAFs (procedures per access: 2.5, 1.0, and 0.6 for AVGs, UAFs, and LAFs, respectively). When used, catheters were required for dialysis for a longer time for UAFs (median catheter days, 36, 53, and 56 for AVGs, LAFs, and UAFs, respectively; P < 0.05). Access flow rates were greater in UAFs (1,247 mL/min; n = 48; P < 0.01) than AVGs (851 mL/min; n = 30) or LAFs (938 mL/min; n = 31). There was no evidence that UAFs were banded or ligated for steal syndromes or heart failure more often than AVGs or LAFs. These results show that the UAF is a good alternative to an AVG for achieving Dialysis Outcomes Quality Initiative guidelines. PMID- 11774108 TI - Hemodynamics in patients with intradialytic hypotension treated with cool dialysate or midodrine. AB - Cool dialysate and midodrine have been used successfully to treat intradialytic hypotension (IDH) in the end-stage renal disease population. However, the exact mechanisms by which these interventions improve hemodynamic stability are not well known. We undertook a study to evaluate the effect of these modalities on intradialytic hemodynamics in patients with documented dialysis-associated hypotension. We used the ultrasound dilution technique to measure cardiac output (CO), central blood volume (CBV), and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 consisted of control (1A) and cool dialysate (1B) studies, whereas phase 2 consisted of control (2A) and midodrine (2B) studies. CO, CBV, and PVR were measured 30 minutes after the initiation of hemodialysis (HD) and 30 minutes before the termination of HD using the HD01 monitor. Blood pressure was measured pre-HD and post-HD. Fourteen patients with documented IDH completed the study. CO and CBV were significantly more preserved in the cool dialysate and midodrine phases compared with control phases. PVR increased in all phases of the study. Declines in mean arterial pressures from pre-HD to post-HD were less with cool dialysate versus control and midodrine versus control. Ultrafiltration volumes were not significantly different between phases. Cool dialysate and midodrine appear to improve intradialytic hemodynamics in patients with dialysis-associated hypotension, mainly through the preservation of CBV and CO, rather than significantly elevating PVR. PMID- 11774109 TI - Evaluation of DOQI guidelines: early start of dialysis treatment is not associated with better health-related quality of life. AB - The National Kidney Foundation-Dialysis Outcomes Quality Initiative (DOQI) guideline, which is largely opinion based, promotes an earlier initiation of dialysis treatment than usual. Implementation of this guideline would require an expansion of dialysis capacity, leading to a considerable increase in costs. Such an expansion can only be justified by an improvement in patient outcome. We studied the effect of late versus timely initiation of dialysis treatment on the course of health-related quality of life (HRQOL) in new dialysis patients. As part of a large Dutch prospective multicenter study (Netherlands Cooperative Study on the Adequacy of Dialysis-2), we consecutively included all new patients with end-stage renal disease for whom residual renal function could be obtained 0 to 4 weeks before the start of dialysis therapy. HRQOL was assessed by means of the Kidney Disease and Quality of Life Short Form at regular intervals during the first year of chronic dialysis treatment. According to the DOQI guideline, 90 of the 237 included patients (38%) started dialysis treatment too late. All patients showed marked improvement in HRQOL during the first 6 months after the start of dialysis treatment. Compared with patients who started dialysis treatment too late, patients who started in time had significantly higher HRQOL for a number of dimensions immediately after the start of treatment. After 12 months of dialysis treatment, these differences had disappeared. An evidence-based recommendation on an early start of dialysis treatment is still difficult to give. In the short term, an earlier start resulted in better HRQOL. However, within 1 year, this advantage had disappeared. It is unclear whether this short-term benefit outweighs the extra restrictions associated with earlier initiation of dialysis therapy. Consequently, only the patient, in consultation with the nephrologist, is able to weigh both sides. PMID- 11774110 TI - Cost-quality trade-offs in dialysis care: a national survey of dialysis facility administrators. AB - Dialysis facilities face important trade-offs between cost and quality under constrained capitated reimbursement. How management at dialysis facilities makes decisions affecting cost and quality of care and views opportunities and threats is unknown. We conducted a national survey of dialysis facility administrators. We asked administrators what changes they would make in response to increases or decreases in reimbursement, their views on linking dialysis care payment to quality-of-care measures, and their views on providing patients with treatment options and outcomes information. One hundred fifty-seven of 280 dialysis facility administrators (56%) responded. If dialysis reimbursement were to increase by 20%, the five most common responses were to: improve patient education programs (62% of respondents), improve facility amenities (42%), purchase new equipment (30%), provide more money for staff salaries (28%), and increase number of nursing staff (21%). Conversely, if dialysis reimbursement were to decrease by 20%, the most common responses were to: limit staff salary (45% of respondents), decrease nursing staff (41%), not replace dialysis equipment (43%), increase dialyzer reuse (37%), and return less to investors (36%). Differences in rank order of responses were observed according to professional training of the administrator and profit status of the facility. Administrators uniformly believe that it is very acceptable to provide facility specific outcomes data to the public, as well as information on modalities of treatment provided by facilities. However, administrators varied in their views regarding whether reimbursement should be based on quality by using a process-of care measure, such as the average dose of dialysis, or an outcome-of-care measure, such as case-mix-adjusted mortality rates. We conclude that increases in facility reimbursement generally would be used by dialysis facility administrators for the benefit of patients, whereas decreases (or inflation erosion) in payment rates might compromise staffing. US dialysis administrators support sharing treatment options and outcomes information with patients, but appear to be ambivalent with regard to linking reimbursement to adequacy of dialysis or patient outcomes. These results have important implications regarding proposed changes in the US capitated dialysis payment rate and current efforts to empower consumers of dialysis care. PMID- 11774111 TI - Vitamin E-bonded hemodialyzer improves neutrophil function and oxidative stress in patients with end-stage renal failure. AB - We evaluated the biocompatibility of a newly developed vitamin E hemodialyzer (CL EE; Terumo Co Ltd, Tokyo, Japan) by neutrophil function and oxidant stress in patients with end-stage renal failure in a randomized crossover study. Ten patients underwent hemodialysis using either the CL-EE or a control dialyzer membrane identical to the CL-EE except for vitamin E binding for 12 weeks in a crossover fashion after a 1-month washout period with hemophane membranes. White blood cell counts, serum oxidized low-density lipoprotein (Ox-LDL) levels, and malondialdehyde (MDA) levels during hemodialysis sessions were measured at the initiation and end of the CL-EE and control trials. Superoxide anion production by neutrophils just before and 4 hours after starting the session also was measured. Leukocytopenia at 1 hour after starting the session was detected to a similar extent in both membranes. However, the degree of reduction was less in the CL-EE trial after repeated use. Superoxide anion production by neutrophils just before a hemodialysis session was reduced after repeated use of the CL-EE membrane. Serum Ox-LDL levels increased, whereas serum MDA levels decreased during sessions to a similar extent in both trials. However, these parameters were significantly lower in the CL-EE trial after repeated use. Serum LDL concentrations significantly decreased with repeated use of the CL-EE membrane. These data suggest that repeated use of the CL-EE membrane for 3 months improves neutrophil function, oxidant stress, and LDL concentrations in patients with renal failure. This membrane may be useful to reduce the incidence of cardiovascular events in patients with renal failure. PMID- 11774112 TI - Vitamin B6 metabolism and homocysteine in end-stage renal disease and chronic renal insufficiency. AB - Homocysteine (tHcy) is a risk factor for atherosclerosis in patients with end stage renal disease and chronic renal insufficiency (CRI). Vitamin B6 deficiency may result in high tHcy levels, especially after a methionine load (PML). Therefore, we evaluated vitamin B6 metabolism and tHcy (fasting and PML) levels in patients with CRI and those on hemodialysis (HD) therapy before and during high-dose sequential vitamin B6 and folic acid supplementation in male patients (27 patients, HD, 17 patients, CRI) and 19 age-matched healthy controls. Vitamin B6 doses were 100 mg/d in patients with CRI and 200 mg/d in HD patients, plus folic acid (5 mg/d), for more than 3 months in each period. We analyzed vitamin B6 metabolites by high-performance liquid chromatography in plasma and red blood cells (RBCs) and fasting tHcy in all cases and PML in subgroups of 11 HD patients and 14 patients with CRI. We found vitamin B6 deficiency and high tHcy (fasting and PML) levels in all patients. Plasma and RBC levels of pyridoxal and pyridoxal phosphate were abnormally low, whereas levels of pyridoxic acid (PA), an end product of vitamin B6 metabolism, were extremely high in both groups. Fasting and PML tHcy levels were partially resistant to vitamin B6 supplements, with different response patterns in HD patients and those with CRI. Thus, the PML defect was more responsive to folic acid in HD patients, whereas vitamin B6 partially reduced PML tHcy levels in patients with CRI. Resistance of tHcy to vitamin B6 treatment in patients with CRI and HD patients is not caused by poor absorption or low tissue stores. Rather, nonvitamin factors or potentially toxic PA levels may be implicated in abnormal vitamin B6 and/or tHcy metabolism during renal insufficiency. PMID- 11774113 TI - Comparison of causes of death using HEMO Study and HCFA end-stage renal disease death notification classification systems. The National Institutes of Health funded Hemodialysis. Health Care Financing Administration. AB - Few data are available on the accuracy of death classification in patients with end-stage renal disease (ESRD). The National Institutes of Health-funded Hemodialysis (HEMO) Study allows the opportunity to compare cause of death recorded on the Health Care Financing Administration (HCFA) Death Notification Form 2746 with death classified by the HEMO Study. The HEMO Study cause of death is determined by trained HEMO Study Outcome Review Committee physicians. In this interim analysis, there were 220 deaths coded by both classification systems. Using the HEMO Study classification system, the most common cause of death was ischemic heart disease (20.4%), followed by arrhythmia and conduction problems (10.4%), cerebrovascular disease (8.6%), and non-access-related infections (7.7%). Using the HEMO Study final death classification as the reference standard, most differences in the two classification systems were related to coding of heart disease. Sensitivity for the HCFA classification ranged from 9.1% for congestive heart failure to 91.7% for malignancy, whereas specificity values were all greater than 78%. Positive predictive values ranged from 11.8% for other heart disease and conditions to 100% for malignancy and hepatobiliary disease, whereas negative predictive values were all greater than 85%. The kappa statistic between the two death classification systems ranged from 0.12 for congestive heart failure to 0.95 for malignancy. Studies using death classification from the HCFA ESRD death notification form for deaths secondary to either cardiovascular diseases or unknown causes should be interpreted cautiously. PMID- 11774114 TI - Bipedal bioelectrical impedance analysis reproducibly estimates total body water in hemodialysis patients. AB - Formal kinetic modeling for hemodialysis patients requires accurate determination of in vivo dialyzer clearance, careful measurement of the actual dialysis time, and calculation of the patient's total body water (V) or urea space. Bipedal (BP) bioelectrical impedance analysis (BIA) is a simple method for the determination of V at the same time the patient is weighed. Because of better correlation with the Watson formula volume and a smaller coefficient of variation than urea kinetic volumes, BP-BIA estimates of V may be preferred in dialysis units that meet guidelines by following formal kinetic modeling data or use V estimates in calculating treatment time. PMID- 11774116 TI - Evaluation of an antimicrobial-impregnated continuous ambulatory peritoneal dialysis catheter for infection control in rats. AB - Infection is the most serious complication arising in long-term continuous ambulatory peritoneal dialysis (CAPD), specifically peritonitis and exit-site infection. The initial weeks after implantation is the crucial period during which bacterial colonization of the catheter results in maximal morbidity, with Staphylococcus aureus being the most virulent organism. We developed an antimicrobial-impregnated CAPD catheter by impregnating the cuff and tubing with chlorhexidine, silver sulfadiazine, and triclosan in a polymer matrix. The antimicrobial spectrum and duration were shown by measuring zones of inhibition to various bacteria and fungi over the course of 5 to 10 days. Activity also was assessed subsequent to soaking in trypticase soy broth containing 20% bovine serum over the course of 1, 3, and 7 days. Significant antimicrobial activity was shown against all organisms tested for, with particular efficacy against gram positive bacteria. Catheters were implanted in rats followed by inoculation of the exit site with S aureus. Seven days postimplantation, 0% of the impregnated catheters were colonized intraperitoneally compared with 100% of the control catheters. Similarly, 12.5% of the impregnated catheters were colonized at the exit site, whereas 100% of the controls were colonized. Histologic analysis showed that this combination and concentration of antimicrobials did not retard healing or cause increased inflammation compared with control catheters after 3, 10, and 24 days postimplantation in noninoculated rats. PMID- 11774115 TI - Effect of combining an ACE inhibitor and an angiotensin II receptor blocker on plasma and kidney tissue angiotensin II levels. AB - Increased angiotensin II (AII) activity has been recognized as a risk factor for progression of kidney disease. There is increasing clinical evidence that combining an angiotensin-converting enzyme (ACE) inhibitor with an AII receptor blocker (ARB) reduces proteinuria and blood pressure in patients with renal disease, although the mechanism of this synergistic effect remains poorly defined. This study tested whether the combination of an ACE inhibitor and an ARB reduces plasma AII (AIIp) and kidney tissue AII (AIIk) beyond what is observed with either of these two agents alone. Mean arterial pressure, glomerular filtration rate, AIIp, and AIIk were measured in four groups of Wistar rats after 2 weeks of a low-salt diet and 1 week of treatment with captopril (2.4 mg/d), losartan (1.7 mg/d), combination captopril+losartan (1.7 mg/d of captopril, 0.7 mg/d of losartan), or no treatment (control). Administration of captopril, losartan, and captopril+losartan produced statistically significant reductions in mean arterial pressure (control, 130 +/- 4 mm Hg; captopril, 92 +/- 5 mm Hg; losartan, 88 +/- 4 mm Hg; captopril+losartan, 104 +/- 5 mm Hg) and mild reductions in glomerular filtration rate (control, 3.1 +/- 0.1 mL/min; captopril, 2.2 +/- 0.3 mL/min; losartan, 1.7 +/- 0.3 mL/min; captopril+losartan, 2.3 +/- 0.3 mL/min) when compared with control rats, but no significant differences were observed among the treated groups. Captopril and captopril +losartan reduced AIIp significantly when compared with control (captopril, 43 +/- 8 pg/mL; captopril+losartan, 47 +/- 5 pg/mL; control, 134 pg/mL) and with losartan (99 +/- 2 pg/mL). AIIk values were reduced in captopril (254 +/- 18 pg/g kidney weight) and losartan (292 +/- 33 pg/g kidney weight) when compared with control (1,235 +/ 79 pg/g kidney weight). Captopril+losartan (136 +/- 17 pg/g kidney weight) reduced AIIk to values significantly lower than captopril or losartan alone. Higher doses of captopril (5 mg/d and 7.5 mg/d) or losartan (4 mg/d and 6 mg/d) alone did not reduce AIIk to the levels observed with combination low doses of captopril+losartan. Combining low doses of ACE inhibitor plus ARB reduces AIIk more than higher doses of either agent alone. This reduction in AIIk with ACE inhibitor plus ARB provides a mechanism to understand the synergism of this combination in reducing proteinuria and blood pressure. The reduction in AIIk with ACE inhibitor plus ARB may have important implications in long-term organ protection in hypertension and renal disease. PMID- 11774117 TI - Increased expression of cell adhesion kinase beta in human and rat crescentic glomerulonephritis. AB - Cell adhesion kinase beta (CAKbeta, also known as Pyk2/CadTK/RAFTK) is the second member of the focal adhesion kinase (FAK) subfamily. We examined the expression of CAKbeta in various human glomerulopathies by immunohistochemistry. Although CAKbeta expression in the normal kidney is confined to the brush border of the proximal tubule with no detectable glomerular staining, we found that glomerular crescents strongly expressed this kinase. Expression of CAKbeta was prominent in cellular crescents but was minimal in fibrocellular or fibrous crescents. Serial section analysis revealed that most CAKbeta-expressing cells were positive for cytokeratin but were negative for CD68 (a macrophage marker), suggesting that CAKbeta was expressed by parietal epithelium in the crescents. We also examined CAKbeta expression in a rat model of crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody. Similar to human nephritis, enhanced expression of CAKbeta in glomerular crescents was apparent. Increased expression of CAKbeta also was confirmed by anti-CAKbeta immunoblotting and by real-time quantitative polymerase chain reaction. Previous studies have shown that CAKbeta is activated by various stimuli regulating cell growth and survival. Although our findings do not determine whether or not increased expression of CAKbeta is a primary event for the development of crescentic glomerulonephritis, further understanding of this pathway may be important to gain novel insights into the factors that promote crescent formation. PMID- 11774118 TI - Crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder. AB - Intracellular crystal formation in histiocytes in multiple myeloma and other lymphoproliferative disorders is an uncommon presentation. In all cases, crystal formation is associated with accumulation of histiocytes containing light chain or immunoglobulin inclusions, and the disorder has been termed crystal-storing histiocytosis. We report a case of crystal-storing histiocytosis affecting the kidney with prominent infiltration of the mesangium by large mononuclear and multinuclear cells that contained eosinophilic crystalline material in the setting of a low-grade B-cell lymphoproliferative disorder. The interstitium did not contain similar crystal-containing histiocytes. On electron microscopy, the mononuclear and multinuclear cells in the mesangium were filled with rhomboid and needle-shaped crystals. Immunofluorescence studies showed the material to be positive for lambda light chains but negative for kappa light chains. To our knowledge, this is the first report of crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder with an immunophenotype of a marginal zone lymphoma and of exclusive expansion of the mesangium by infiltrating histiocytes containing needle-shaped and rhomboid crystals that were positive for lambda light chains. We report this case to illustrate an unusual finding of mesangial infiltration by crystal-storing histiocytes, and we review the literature of renal involvement by crystal-storing histiocytosis and crystal deposition in lymphoproliferative disorders. PMID- 11774119 TI - A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings. AB - A 40-year-old woman was referred for several episodes of coma lasting from 2 hours to 2 days. She had been on maintenance hemodialysis for polycystic kidney disease for 9 months. Laboratory findings showed high serum levels of ammonia and citrulline, and a diagnosis of adult-onset type II citrullinemia was made. Multiple areas of focal brain edema were shown by magnetic resonance imaging. The clinical manifestations of coma and abnormal behavior were resolved with intensified dialysis (ie, four 5-hour sessions per week with glycerol and continuous ambulatory peritoneal dialysis). No abnormal shadow was present on follow-up magnetic resonance imaging. Such intensified dialysis therapy may be effective for adult-onset type II citrullinemia and may be applicable even in patients who do not have end-stage renal disease if liver transplant is not an option. PMID- 11774121 TI - L-arginine-nitric oxide pathway in end-stage renal disease. PMID- 11774123 TI - Renal insufficiency with monoclonal gammopathy and urticarial vasculitis. PMID- 11774125 TI - Progression of vascular calcification and dyslipidemia in patients on chronic hemodialysis. PMID- 11774126 TI - Combined use of enalapril and losartan to reduce proteinuria: a question of safety. PMID- 11774128 TI - Electrophoretic pattern of concentrated urine: comparison between 24-hour collection and random samples. AB - The electrophoretic pattern of concentrated urine samples can be used to identify the type of proteins leaking into the urine and has diagnostic and prognostic value, providing information about the location (glomerular or tubular) and degree of renal injury. This test usually requires a 24-hour urine collection, which can be inconvenient because of its heavy dependence on patient compliance and frequently is unreliable because of errors in collecting a complete 24-hour urine sample. In this study, we compared the electrophoretic pattern in 24-hour urine collections and random samples among patients with glomerular diseases and a wide range of proteinuria. Forty adult patients were evaluated; 24-hour urine collections and random urine samples were analyzed. Protein concentrations were determined using the sulfosalicylic acid method standardized with human serum. Electrophoresis was performed with concentrated urine samples (Ultrafree, PF/Millipore Corporation, Bedford, MA) using Beckman Paragon Electrophoresis System (agarose gels and blue staining; Beckman Instruments, Inc, Brea, CA). Densitometric scanning of electrophoretic pattern (Appraise Clinical Densitometer; Beckman Instruments, Inc) was performed, and the results were reported in percentages of each observed fraction. Our results revealed that despite the significant difference between protein concentration in 24-hour collections and in random samples, the pattern of protein excretion, in percentage basis, remains the same. There were no differences between the albumin, alpha(1)-globulin, alpha(2)-globulin, beta-globulin, and gamma-globulin fractions in both types of specimens. This study shows that, at least in glomerular proteinuria, the electrophoretic analysis of the urine can be performed accurately in random samples, avoiding the inconveniences and errors of a 24-hour urine collection. PMID- 11774129 TI - Asymptomatic cystic fibrosis diagnosed in an adult evaluated for hematuria. AB - We report a case of cystic fibrosis in an asymptomatic man evaluated for hematuria with infertility. The ever-broadening spectrum of atypical adult presentations of cystic fibrosis should prompt physicians to have a lower threshold for ordering genetic screening for cystic fibrosis transmembrane regulator (CFTR) gene mutations. PMID- 11774130 TI - Myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis superimposed on biopsy-proven diabetic nephrosclerosis. AB - We present a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO ANCA)-associated glomerulonephritis with diabetic nephrosclerosis, diagnosed by serial renal biopsies within a short period. A 78-year-old man with renal insufficiency, who had been diagnosed with diabetic nephrosclerosis by renal biopsy 9 months earlier, was admitted to the hospital for dyspnea and rapid deterioration of renal function. The titer of serum MPO-ANCA was high, and the second renal biopsy confirmed the presence of necrotizing glomerulonephritis with crescents. Methylprednisolone pulse therapy followed by oral administration of prednisolone led to resolution of respiratory symptoms and reversal of MPO-ANCA. Renal function did not improve, however, necessitating hemodialysis. A review of the literature showed several cases of necrotizing glomerulonephritis superimposed on diabetic nephropathy but only a few reported cases of MPO-ANCA glomerulonephritis associated with diabetic nephrosclerosis. Diabetic patients who show rapid deterioration of renal function should undergo renal biopsy to determine the concomitant presence, if any, of other glomerular diseases and to prevent life-threatening systemic involvement. PMID- 11774131 TI - Malignancy after renal transplantation. AB - Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression. PMID- 11774134 TI - Anterior internal impingement: An arthroscopic observation. AB - PURPOSE: The source of pain in patients with a stable shoulder and clinical signs of impingement is traditionally thought to be subacromial or outlet impingement, as popularized by Neer. This report introduces the concept of anterior internal impingement in patients with signs and symptoms of classic impingement syndrome and arthroscopic evidence of articular-side partial rotator cuff tear. Contact that occurs between the fragmented undersurface of the rotator cuff and the anterosuperior labrum is the apparent source of pain in these patients. TYPE OF STUDY: Case series. METHODS: Ten patients with a primary symptom of pain and an arthroscopic finding of a partial rotator cuff tear were reviewed. Arthroscopic visualization of the subacromial space revealed no evidence of subacromial impingement or bursitis in any patient. All patients had clinical signs and symptoms of classic impingement. The initial part of the surgical procedure consisted of a complete diagnostic arthroscopy in a low-volume gas medium using a single posterior portal. While performing the Hawkins test, the locations of any areas of abnormal soft-tissue contact and impingement were observed directly. RESULTS: There was anterior internal impingement in all 10 patients with partial thickness rotator cuff tears. The abnormal and fragmented rotator cuff tissue made contact with the anterior superior labrum when the shoulder was visualized from the posterior portal while performing the Hawkins test. Preoperative magnetic resonance imaging correctly showed a partial-thickness rotator cuff tear in 20% of the cases. CONCLUSIONS: Recognition of anterior internal impingement as a clinical entity is important because magnetic resonance imaging results are often misleading. This is of particular importance in young patients with isolated lesions in whom arthroscopic acromioplasty and capsular reefing procedures would be unnecessary. When anterior internal impingement is recognized as the source of unresolved shoulder pain, patient selection for surgery and procedure selection can be improved. PMID- 11774135 TI - The use of the impingement test as a predictor of outcome following subacromial decompression for rotator cuff tendinosis. AB - PURPOSE: To evaluate the use of the impingement test as a predictor of outcome following subacromial decompression for patients with rotator cuff tendinosis. TYPE OF STUDY: Observational study. METHODS: An impingement test was administered to each patient immediately before surgery. Patients underwent a subacromial decompression and were assessed postoperatively at 3 and 6 months. The primary outcome measure was the Western Ontario Rotator Cuff Index (WORC). RESULTS: Thirty patients (mean age, 47.0 years; range, 29.4 to 71.2 years) took part in this study. There was no significant correlation between the classic impingement test (Neer's impingement sign before and after subacromial injection of local anesthetic) and the change in WORC score (r = -.174, P =.358). Similar results were obtained for the aggregate impingement test (pain at rest plus Neer's impingement sign plus Hawkins sign plus resisted abduction) before and after subacromial injection of local anesthetic (r = -.208, P =.270). When divided into categories of improvement following the classic impingement test (worse 0%-25%, 26%-50%, 51%-75%, 76%-100% better), there was no significant difference between groups for outcome as indicated by WORC score (P =.203). Results were similar for the aggregate impingement test (P =.271). CONCLUSIONS: The impingement test is a poor tool for predicting the success of subacromial decompression. There are 6 assumptions discussed that must hold true in order for the impingement test to be a useful predictor of outcome following subacromial decompression. If one or more of these assumptions are not met, or are only partially met, the impingement test would be rendered invalid as a predictor of outcome, as this study suggests. PMID- 11774136 TI - The correlation between bursoscopic and histologic findings of the acromion undersurface in patients with subacromial impingement syndrome. AB - PURPOSE: Ideally, decompression of the coracoacromial arch in patients with shoulder impingement syndrome should be done only at the site of impingement. However, it is very difficult to determine the exact site of impingement before acromioplasty. The objectives of this study were to investigate the relationship between findings and the histopathologic changes of the undersurface of the acromion in subacromial impingement syndrome and to evaluate the usefulness of bursoscopy in identifying the site of the impingement. TYPE OF STUDY: Case series. METHODS: We investigated the correlation between subacromial bursoscopic findings and histopathologic changes of the coracoacromial arch in 50 patients with subacromial impingement syndrome. The acromion and the coracoacromial ligaments removed during acromioplasty were fixed in 10% formalin, decalcified, embedded in paraffin, and cut into sections along the direction of the coracoacromial ligament. After staining with toluidine blue, the specimens were evaluated for pathology using an optical microscope. RESULTS: The pathologic changes were classified into 3 types according to the direction of proliferative fibrocartilaginous changes at the enthesis of the acromial insertion of the coracoacromial ligament. The bursoscopic findings were classified into 4 types. Subacromial abnormalities in the bursoscopy findings correlated with histopathologic changes at the undersurface of the acromion. On the other hand, cases with normal findings on the undersurface of the acromion on bursoscopy had hypertrophic changes of fibrocartilage at the insertion of the coracoacromial ligament to the acromion. These results suggest that, with normal findings on the undersurface of the acromion in patients with subacromial impingement syndrome, there is impingement at the coracoacromial ligament. CONCLUSIONS: Bursoscopy is a useful procedure to determine the impingement site in patients with subacromial impingement. PMID- 11774137 TI - Arthroscopically assisted mini-open rotator cuff repair. AB - PURPOSE: To review the results of arthroscopically assisted mini-open rotator cuff repair. TYPE OF STUDY: Retrospective clinical review. METHODS: From 1990 to 1994, 67 patients (69 shoulders) had a rotator cuff repair for a full-thickness tear; 63 of these patients had an arthroscopically assisted mini-open rotator cuff repair. Of these, 22 were lost to follow-up; thus, 41 patients were retrospectively reviewed for this study. The average patient age was 51 years and the average follow-up was 36 months. UCLA scores incorporating preoperative and postoperative pain, function, strength, and range of motion data were used to analyze the results. RESULTS: At follow-up, 38 patients (93%) were rated as excellent or good, 3 patients (7%) were rated as fair, and none was rated as poor. All patients showed improvement in pain and function after surgery and all of the patients were satisfied with the procedure. The average UCLA score was 32.3. There was a small but significant (P <.0001) difference between UCLA scores of Workers' Compensation patients (UCLA score, 29; n = 11) versus noncompensation patients (UCLA score, 33; n = 30). In addition, the return-to-work interval was prolonged in the Workers' Compensation cases. There were no significant differences in UCLA scores on the basis of tear size (P <.4286) or patient age (P <.1131). CONCLUSIONS: Our data suggest that the arthroscopically assisted mini open technique for rotator cuff repair is an excellent approach for repair of a torn rotator cuff. PMID- 11774138 TI - Outcome of first-time endoscopic carpal tunnel release in a teaching environment. AB - PURPOSE: The purpose of this study was to dissect cadaver hands used in the teaching of the Chow endoscopic carpal tunnel release (ECTR) technique and determine the adequacy of transverse carpal ligament (TCL) release and any complications. TYPE OF STUDY: Cadaveric study. METHODS: ECTR was performed on 573 cadaver hands using either the transbursal Chow technique (n = 147) or the extrabursal Chow technique (n = 426). After dissection, the adequacy of the TCL release and any complications were recorded. RESULTS: With the transbursal technique, 58% of the specimens had a complete TCL release. Complications were noted in 11 specimens (7%). Using the extrabursal technique, 70% of the specimens had a complete TCL release. Complications were noted in 15 specimens (4%). The difference in complication rates between the transbursal and extrabursal techniques was significant (P <.05) as was the incidence of partial release (P <.01). CONCLUSIONS: The extrabursal Chow technique is preferred and practice on cadaver specimens is recommended before clinical application. PMID- 11774139 TI - The diagnostic dilemma created by osteoid osteoma that presents as knee pain. AB - PURPOSE: Osteoid osteoma is a rare benign bone lesion with a high incidence in adolescents and young people. The objective of our study was to illustrate the difficulties in diagnosis of osteoid osteoma in patients presenting with atypical knee pain. TYPE OF STUDY: Retrospective case series. METHODS: In 10 patients who presented to our department with atypical knee pain between 1984 and 1999, the diagnosis of an osteoid osteoma was delayed. Retrospective review of these 10 cases was performed using interviews and re-evaluation of medical histories, radiographs, computed tomography (CT) scans, isotope bone scan, and magnetic resonance imaging (MRI). RESULTS: Initial radiographs showed features of osteiod osteoma in only 2 cases. In addition, in 1 case, not only initial but also repeated radiographs of the knee joint were still normal 10 months after the delineation of the nidus using MRI. Four unnecessary arthroscopies were performed on 4 of the 10 patients and the final diagnosis was established using MRI, CT, and isotope bone scan. The mean time interval between arthroscopy and osteiod osteoma diagnosis was 11.5 months. CONCLUSIONS: Osteoid osteoma must be included in the differential diagnosis of persistent unexplained knee pain, especially when objective findings of the knee are vague. The presence of the lesion juxta articular to the knee joint or in the midshaft or upper end of the femur may be referred as pain to a nearby joint. Plain radiographs have a low diagnostic value in the detection of the lesion whereas isotope bone scan and MRI are reliable imaging techniques. The evaluation of the ipsilateral hip joint should not be overlooked. PMID- 11774140 TI - Serial magnetic resonance imaging evaluation of the patellar tendon after posterior cruciate ligament reconstruction. AB - PURPOSE: Our purpose was to prospectively analyze serial changes in magnetic resonance imaging (MRI) signal of the bone-patellar tendon-bone autograft when used for posterior cruciate ligament (PCL) reconstruction and to retrospectively determine at mid-term follow-up the relationship between MRI graft appearance and clinical stability in patients who have undergone arthroscopic PCL reconstruction with a bone-patellar tendon-bone autograft. TYPE OF STUDY: One prospective serial blinded study and 1 retrospective blinded study. METHODS: The first part of the study focused on MRI scans obtained at 3, 6, 9, and 12 months postoperatively in a case series of 10 consecutive patients who underwent arthroscopically assisted PCL reconstruction (group A), and of 10 patients who underwent combined ACL-PCL arthroscopic reconstruction (group B). For the second part of the study, MRI scans were obtained in a retrospective series of 10 patients at mid-term follow up after PCL arthroscopic reconstruction (group C). Signal intensity of 3 zones, corresponding to the proximal, middle, and distal intra-articular graft zones, was evaluated according to the Howell et al. classification. Fiber continuity assessment was performed using a modified Kuhne et al. score. The signal intensity of the 3 zones was independently scored. Knee stability was clinically and instrumentally graded according to the IKDC evaluation form (group 4). A multivariance analysis and grouped t test were used for statistical evaluation. RESULTS: In group A, the average MRI evaluation score was 7.65 +/- 1.6 at 3 months, 3.8 +/- 0.6 at 6 months, 4.75 +/- 1 at 9 months and 6.25 +/- 1.2 at 1 year. The portion of graft exiting the femoral tunnel exhibited increased signal and faster maturation than the tibial tunnel. In group B (combined ACL-PCL reconstruction), the graft showed slower graft healing with an average MRI score of 4.85 +/- 0.7 at 3 months, 1.9 +/- 0.7 at 6 months, 3.9 +/- 0.9 at 9 months, and 5.3 +/- 1.1 at 1 year. At 1 year follow-up, there was no correlation between MRI appearance and stability in group A, even with MRI findings of fiber continuity. However, at long-term evaluation (group C), a strict correlation between MRI appearance and achieved stability was found. CONCLUSIONS: The patellar tendon when used for PCL reconstruction requires more than 1 year to achieve a low-signal intensity over its entire course, and the distal zone near the tibial tunnel shows a slower healing process. MRI graft assessment is useful only 1 year or more following PCL reconstruction. PMID- 11774141 TI - Reconstruction of the anterior cruciate ligament in females: A comparison of hamstring versus patellar tendon autograft. AB - PURPOSE: To compare the clinical results of anterior cruciate ligament reconstruction in female patients using quadruple-looped hamstring autograft versus patellar tendon autograft at minimum 2-year follow-up. TYPE OF STUDY: Case series. METHODS: A prospective clinical review was performed to compare the results of ACL reconstruction with hamstring versus patellar tendon autograft in a group of female patients. Exclusion criteria included chronic injuries (greater than 3 months), associated collateral ligament injuries, Workers' Compensation or litigation cases, and bilateral anterior cruciate ligament injuries. There were 39 female patients in the hamstring group (average follow-up, 40.9 months) and 37 female patients in the patellar tendon group (average follow-up, 52 months). Both types of grafts were fixed with an EndoButton proximally and with sutures tied over a post or button distally. The postoperative rehabilitation regimen was identical for both groups. Objective parameters evaluated included preinjury and postoperative Tegner and Lysholm scores, side-to-side KT-1000 maximum-manual arthrometer differences, and clinical examination including Lachman and pivot shift tests. Graft failure was defined by any one of the following: a KT-1000 difference of greater than 5 mm, a 2+ Lachman, a 1+ or greater pivot shift, or revision surgery. RESULTS: The failure rate in the hamstring group was 23% versus 8% in the patellar tendon group, which was not statistically significant (P >.1). Comparison of preinjury Tegner activity scores to postoperative scores revealed that patients in the hamstring group did not return to their preinjury level of activity (preinjury 6.54 v postoperative 5.17) as well as patients in the patellar tendon group (preinjury 6.20 v postoperative 6.59). Patients in the hamstring group had a significant increase in pain compared with the patellar tendon group (P =.034). CONCLUSIONS: Although not statistically significant, the hamstring group had more failures, more laxity on clinical examination, and more patients with larger KT-1000 arthrometer differences. These results indicate a trend toward increased graft laxity in female patients undergoing reconstruction with hamstring autograft compared with patellar tendon when evaluated by a single surgeon using similar fixation techniques at short- to medium-range follow-up. More studies with larger patient numbers using current fixation techniques are necessary to confirm these findings. PMID- 11774142 TI - The effect of anterior cruciate ligament graft rotation on knee laxity and graft tension: An in vitro biomechanical analysis. AB - PURPOSE: The purpose of this study was to determine the effects of rotating a bone-patellar tendon- bone allograft during anterior cruciate ligament reconstruction on anteroposterior (AP) knee laxity and forces developed within the graft. TYPE OF STUDY: In vitro biomechanical study using human cadaveric knees. METHODS: Thirteen fresh-frozen knee specimens received bone-patella tendon bone allografts that were pretensioned at 30 degrees of flexion to restore AP laxity to that of the intact knee. AP laxity was then measured at 0 degrees, 30 degrees, and 90 degrees of knee flexion with the graft in neutral rotation and in 90 degrees and 180 degrees of internal and external rotation. Five specimens received allografts that were rotated to 90 degrees internally and externally and then tensioned. Two knee specimens were used to measure the effects of graft rotation on graft force at full extension; 1 received 7 separate allografts and the other received 10 allografts. During testing, the potted end of the allograft that was connected to a tibial load cell was rotated. RESULTS: In specimens tensioned and then rotated, AP laxity at 30 degrees of knee flexion decreased an average of 0.9 mm with 90 degrees of graft rotation in either direction. At 180 degrees of external rotation, the mean decrease in laxity of 1.8 mm was significantly greater than that for 180 degrees of internal rotation (P <.05). When significant, all mean laxity reductions at 0 degrees and 90 degrees of flexion were less than those at 30 degrees of flexion. In specimens where the graft was rotated and then tensioned, rotation had no significant effect on laxity. With the exception of 90 degrees of external rotation, rotation of the graft increased graft tension at full extension; 90 degrees of internal rotation increased mean graft force by 11 N (P <.05). Rotating the graft 180 degrees in either direction increased mean graft force at full extension by 25 N (P <.05). CONCLUSIONS: Although minor, rotating the graft had significant effects on knee laxity and graft tension. In general, AP laxity decreased and graft tension increased with increasing rotation of the graft. The direction of rotation did not seem to be important. As a result, clinicians who choose to rotate their patellar tendon grafts can expect that the biomechanical changes in the graft with rotation will have little clinical importance. PMID- 11774143 TI - Synovial response to intra-articular metal debris: Implications for anterior cruciate ligament reconstruction. AB - PURPOSE: Intra-articular metal debris is occasionally seen after completion of an endoscopic anterior cruciate ligament reconstruction. The purpose of this study was to examine the tissue response to intra-articular stainless steel metal debris in order to better understand its role in the inflammatory process. TYPE OF STUDY: Animal case control study. METHODS: Metal filings created from a Beath pin were injected into 10 rabbit knees. The opposite knee of each rabbit was used as a control. The animals were killed at 4 weeks. The knee joints were fixed, sectioned, stained, and examined under light microscopy. RESULTS: Mild to moderate levels of synovial proliferation were observed in all knees injected with metal particles. There was no evidence of phagocytosis of the metal particles, nor was there any evidence of an inflammatory response. No articular cartilage damage was observed as a result of the metal debris. CONCLUSIONS: We believe that the few particles of stainless steel that may be produced during the reaming process in anterior cruciate ligament reconstruction do not pose a significant risk of inciting an inflammatory reaction or cause articular cartilage damage within the knee joint. PMID- 11774144 TI - Two-year follow-up of meniscal repair using a bioabsorbable arrow. AB - PURPOSE: The value of meniscal repair is well established. Several all-inside arthroscopic techniques have become available to achieve this goal. One such technique involves the use of a biodegradable polylactic acid tack, which has made repair technically easier to perform. This study evaluates the 2-year results of arthroscopic meniscal repair using this device. TYPE OF STUDY: Retrospective case series. METHODS: We reviewed charts of 38 patients who had undergone 39 meniscal repairs with the bioabsorbable arrow. All procedures were performed by one of 4 fellowship-trained sports medicine orthopaedic surgeons in 1 of 2 affiliated hospitals, with a minimum follow-up of 2 years. Review consisted of evaluation of patient records, interview, and clinical examination by an independent examiner. Lysholm and Tegner knee scores were recorded. Complications and clinical failure, defined as reoperation, were noted. RESULTS: The average age of the patients was 29.9 years. The ratio of medial to lateral meniscal repair was 5:1. Twenty-one patients underwent concurrent anterior cruciate ligament reconstruction, and in this subgroup, there were no clinical failures. In the remaining group, isolated meniscal repairs in stable knees, the clinical failure rate was 7% (2 reoperations). Local soft-tissue complications occurred in 31.6% of patients, including 2 with arrow migration through the skin. These symptoms typically resolve over several months. CONCLUSIONS: The availability of sutureless all-inside absorbable techniques for meniscal repair has made the procedure technically easier to perform arthroscopically. In our patients, local complications related to device migration, device prominence, and soft-tissue inflammation associated with absorption of the device were common (31.6%). These complications were usually transient. We emphasize the importance of selecting the correct length of device so as to minimize these effects. As with other meniscal repair techniques, a higher success rate was found in knees undergoing concurrent anterior cruciate ligament reconstruction. Our results show a clinical success rate using an absorbable all-inside technique with an absorbable device comparable to reported results using established inside-out techniques. PMID- 11774145 TI - Analysis of arthroscopically assisted ankle arthrodesis. AB - PURPOSE: Evaluation of an arthroscopically assisted ankle arthrodesis technique for clinical and radiographic union, function, and patient satisfaction. TYPE OF STUDY: Retrospective analysis and review of the literature. METHODS: Twenty-one patients with a mean age of 52.7 years who underwent arthroscopic ankle arthrodesis were examined at an average follow-up time of 34 months. The mean duration of symptoms was 4.4 years. The most common diagnosis for patients who underwent arthrodesis was post-traumatic arthritis (19 of 21) with 1 patient having a diagnosis of avascular necrosis of the talus and the other patient having rheumatoid arthritis. All patients described severe mechanical pain as the most important reason for undergoing the procedure. RESULTS: Fusion occurred in 20 of 21 patients. The average time to clinical and radiographic union was 8.9 weeks. Nine patients were graded as excellent; no pain, limp, or occupational restriction, and a stable fusion. Eleven were graded as good; mild pain, occasional limp, or occupational restriction with a stable fusion. One was graded as poor; failed union and pain. The failure had extensive avascular necrosis involving approximately 50% of the talus as a preoperative diagnosis. CONCLUSIONS: The advantages of the arthroscopic technique include a high fusion rate, decreased time to fusion, and decreased cost. There are considerable advantages to the arthroscopic technique in appropriately selected patients with no or mild angular deformity and no avascular necrosis greater than 30% of the talus. There is a substantial reduction in time to fusion in the arthroscopic procedure compared with published reports on open procedures for ankle arthrodesis. While this procedure is not indicated in all instances, selected patients with disabling ankle arthrosis may be more appropriately treated with an arthroscopic arthrodesis than by open surgery. PMID- 11774146 TI - The effectiveness of an anesthetic continuous-infusion device on postoperative pain control. AB - PURPOSE: To evaluate the effectiveness of an anesthetic continuous-infusion device on postoperative pain after outpatient shoulder surgery. TYPE OF STUDY: Double-blinded randomized trial. METHODS: A prospective, double-blinded, randomized study of 50 consecutive patients undergoing outpatient arthroscopic shoulder surgery was performed. Patients were assigned by computer-generated randomized permuted block of four to 2 groups (25 each) receiving either a saline or 0.5% bupivacaine solution via an infusion pump after surgery. All patients gave informed consent and were randomized immediately before surgery. The surgical team, patient, clinic staff, and data collector were blinded to the randomization. Procedures performed included arthroscopic rotator cuff repairs, SLAP lesion repairs, subacromial decompressions, and capsular reefings. The infusion pump that was tested was used continuously for 48 hours and administered 2 mL each hour. For subacromial and rotator cuff surgery, the catheter was placed in the subacromial space. For glenohumeral surgery, the catheter was placed in the glenohumeral joint. Routine pain-control efforts were continued. Interviews were conducted at 1, 2, and 8 hours after surgery, followed by daily telephone interviews for 1 week. Visual analog scale (VAS), categorical pain scale (Likert) data, and oral medication use data were recorded. RESULTS: Complete data sets were collected from 25 bupivacaine and 24 saline patients because 1 pump malfunctioned and was removed early. The average age of the bupivacaine group patients was 47.4 +/- 16.3 years (range, 16 to 84); patients in the saline group had an average age of 46.0 +/- 15.5 years (range, 19 to 73). There were 17 men and 8 women in the bupivacaine group and 16 men and 8 women in the saline group. The Likert and VAS mean values showed lower pain scores for the patients using the pump containing bupivacaine than for the saline group at all recorded times (P <.05) throughout the 7 days of data collection. The interval of greatest pain was on day 2. Postoperative oral medication use was always greater for the saline group than for those receiving bupivacaine. CONCLUSIONS: Postoperative pain control after arthroscopic shoulder surgery is essential so that these procedures can be successfully carried out in an outpatient setting. The first 2 postoperative days is the period of greatest pain. Continuous postoperative bupivacaine infusion is effective during this critical period, and the effect lingers even after the infusion is discontinued. The administration of bupivacaine via a continuous-infusion anesthetic pump statistically reduced postoperative pain after outpatient arthroscopic rotator cuff repairs, SLAP lesion repairs, subacromial decompressions, and capsular reefings. PMID- 11774147 TI - The influence of mechanical stress on graft healing in a bone tunnel. AB - PURPOSE: To examine the relationship between mechanical stress and tendon-bone healing. TYPE OF STUDY: Histologic animal study. METHODS: Forty-four female Japanese White rabbits underwent transplantation of the extensor digitorum longus tendon into a tibial bone tunnel created perpendicular to the long axis of the bone. After surgery, the animals were returned to their cages and were free to move about without any restriction or immobilization of their extremities. The morphologic differences in tendon-bone junctions in terms of location and time were evaluated at 4, 6, 8, and 12 weeks, and at 6 months. RESULTS: At 4 and 6 weeks, abundant collagen-fiber continuity between the graft and the bone was observed at the upper side of the bone tunnel. These fibers resembled Sharpey fibers. The lower side of the tunnel showed a layer of chondroid cells and newly formed woven bone. At 8 and 12 weeks, the collagen-fiber continuity of the upper side of the tunnel had become attenuated, but it was more organized at the entrance. At the lower side, the woven bone layer was still present at the entrance but had disappeared inside the tunnel. At 6 months, regenerated tendon bone junction was observed only at the entrance; a direct type of insertion was observed only at the upper side. The interface tissue inside the tunnel had disappeared on both sides. CONCLUSIONS: Stress distribution in the bone tunnel was thought to be compressive on the lower side and tensile on the upper side at the entrance, and shear force is dominant inside the tunnel. A comparison of histology and stress distribution suggests that tensile stress enhances the healing process of tendon-bone junctions, compressive stress promotes chondroid formation, and shear load has little or no effect on regeneration of the tendon bone junction. PMID- 11774148 TI - Postmeniscectomy osteonecrosis. AB - In the last few years, postmeniscectomy osteonecrosis has been reported, especially in elderly patients, with low incidence, unclear physiopathology, and without long periods of follow-up. We report a case diagnosed and followed-up for a 3-year period using magnetic resonance imaging. In the initial phase, a large area of intramedullary edema was evident; after 3 months, the edema had decreased (it was no longer evident at 1 year examination) and a clearly defined area of osteonecrosis was evident with very high signal intensity on high-contrast sequences. After 3 years, the lesion showed a degenerative cyst appearance with an osteosclerotic rim and completely disrupted cartilage. PMID- 11774149 TI - Evaluation of donor site intrinsic healing response in autologous osteochondral grafting of the knee. AB - We report the case of a 45-year-old male patient who underwent autologous osteochondral autografting in the knee for osteochondritis dissecans. The patient required revision surgery 1 year postoperatively, which allowed histologic and mechanical characterization of the intrinsic healing response of the initial graft donor sites. Histologic examination showed heterogeneous areas of dense fibrous tissue, bone, and discrete areas of cartilage. Mechanical testing using a confined compression testing technique determined the equilibrium stiffness as 0.97 MPa. The majority of dense fibrous tissue and areas of bone are likely responsible for the observed increased stiffness. When performing osteochondral autografting, consideration must be given to the benefit afforded to improving the areas of cartilage injury with the potential morbidity associated with graft harvest at the donor sites. PMID- 11774150 TI - The medial meniscal root as a landmark for tibial tunnel position in posterior cruciate ligament reconstruction. AB - As a result of improved basic science knowledge and operative techniques, posterior cruciate ligament (PCL) reconstructions have steadily increased over the past 10 years. Even for the experienced arthroscopist, PCL reconstruction surgery can be technically challenging and fraught with complications. The most technically demanding aspect of the procedure may be placement and drilling of the tibial tunnel. Reasons for this include unfamiliarity with the posterior aspect of the knee, neurovascular risk, and the relative infrequency of the procedure being performed by most surgeons. We propose that the root of the posterior horn of the medial meniscus is an easily identifiable visible landmark that can not only aid in the localization of the position of the tibial tunnel in PCL reconstruction but also assist navigation in the posterior aspect of the knee arthroscopically. PMID- 11774151 TI - Allograft anterior tibialis tendon with bioabsorbable interference screw fixation in anterior cruciate ligament reconstruction. AB - For a variety of reasons, bone-patellar tendon-bone and Achilles tendon allografts have been used more commonly in anterior cruciate ligament reconstruction. Soft-tissue allografts used mainly are the semitendinosus, gracilis, and occasionally the quadriceps tendons. The anterior tibialis tendon is a thick, strong tendon that can be prepared with one doubling of the graft, has a large cross-sectional area, and has been shown to be stronger than semitendinosus, gracilis, patellar tendon, and native anterior cruciate ligament. Use of allograft shortens surgical time, eliminates graft harvest-site morbidity, and allows for a large supply of grafts for repeat or multiple ligament procedures. This graft can be fixed to the femoral and tibial bone tunnels with bioabsorbable interference screws for a hardware-free, completely endoscopic procedure. Two- to 4-year results of allograft procedures are comparable to autograft procedures, and there have been no early failures with this described technique using anterior tibialis tendon. PMID- 11774154 TI - Trivalent reconstruction for posterolateral and lateral knee instability. AB - Chronic posterolateral rotatory and lateral instability of the knee is approached from multiple anatomic and functional points of view. Traditional surgical techniques provide one-directional stabilization using autologous tendon transplantation and the split-tendon biceps procedure. Both of these resolve the lateral opening of the joint but do not secure the rest of the anatomic structures that are very important, such as the arcuate ligament and the capsule. This new approach to solving an old problem acts by tightening the fibular collateral ligament, arcuate ligament, the capsule (partially), and biceps tendon in 1 step by performing an oblique fibular-head osteotomy and pulling down these structures with good results. We report 2 cases in which this technique was used. The first was a 26-year-old man who hit the dashboard in an automobile accident and presented 1 week later with posterolateral instability associated with a tear of the posterior cruciate ligament. The second was a case of pure chronic lateral instability of the knee in a 32-year-old man who sustained a fall that caused a rupture of his lateral collateral ligament. This was repaired using a trivalent reconstruction at 3 months. Both patients successfully achieved good stability after reconstruction. PMID- 11774155 TI - Fully arthroscopic stabilization of the patella. AB - The authors present a new fully arthroscopic technique for the treatment of patellofemoral instability consisting of plication of the medial patellar retinaculum and release of the lateral patellar retinaculum. The indication for this procedure is not only acute patellar luxation, but also recurrent patellar luxation and subluxation. The procedure has been performed on 17 patients, 6 male and 11 female, between the ages of 14 and 27 years. The indication for surgical arthroscopic treatment was patellar instability in 3 patients, acute patellar luxation in 4, and recurrent patellar luxation in 10 patients. Postoperative results after follow-up of 12 to 26 months have been good with no recurrence of subluxation or luxation. This procedure is a valuable technique for treating patellar maltracking and instability and acute and recurrent patellar luxation, particularly in adolescents and young adults. PMID- 11774156 TI - A new technique for posterior cruciate ligament reconstruction. AB - We describe a new technique for arthroscopically assisted posterior cruciate ligament reconstruction. We use the TransFix (Arthrex, Naples, FL) pin to provide a single and strong tibial attachment point for the 4-stranded semitendinosus and gracilis tendons. The TransFix technique for anterior cruciate ligament reconstruction has been found to give better initial fixation strength than other techniques using semitendinosus and gracilis grafts, and it provides adequate graft length for secure fixation. Strong and secure graft fixation in knee ligament reconstruction is very important for early and fast rehabilitation. PMID- 11774157 TI - Broken blade in the knee: A complication of arthroscopic meniscectomy. AB - Arthroscopic surgery has a very low incidence of intraoperative complications. However, while the authors were using a No. 11 blade to resect the anterior horn of a meniscus, the blade broke and the fragment flew into the posterior knee compartment. The only way to remove it was to make an incision over the popliteal area. We describe this complication to show that improvisation and use of inappropriate surgical instruments can lead to serious problems and the failure of arthroscopic procedures. PMID- 11774158 TI - A novel surgical procedure for osteochondritis dissecans of the lateral femoral condyle: Exchanging osteochondral plugs taken from donor and recipient sites. AB - We treated a 16-year-old boy who had a large symptomatic osteochondritis dissecans (OCD) lesion of the lateral femoral condyle by exchanging osteochondral plugs taken from the donor site with plugs taken from the recipient site. At final inspection 36 months after surgery, he had full range of motion and no symptoms in his knees. Our methods can be used to treat grade 2 or 3 OCD lesions, as classified by Clanton and DeLee. PMID- 11774159 TI - Telepathology overview: from concept to implementation. AB - Telepathology is the practice of pathology at a distance by using video imaging and telecommunications. Significant progress has been made in telepathology. To date, 12 classes of telepathology systems have been engineered. Rapid and ultrarapid virtual slide processors may further expand the range of telepathology applications. Next-generation digital imaging light microscopes, such as miniaturized microscope arrays (MMA), may make virtual slide processing a routine laboratory tool. Diagnostic accuracy of telepathology is comparable with that of conventional light microscopy for most diagnoses. Current telepathology applications include intraoperative frozen sections services, routine surgical pathology services, second opinions, and subspecialty consultations. Three telepathology practice models are discussed: the subspecialty practice (SSP) model; the case triage practice (CTP) model; and the virtual group practice (VGP) model. Human factors influence performance with telepathology. Experience with 500 telepathology cases from multiple organs significantly reduces the video viewing time per case (P < .01). Many technology innovations can be represented as S-curves. After long incubation periods, technology use and/or efficiency may accelerate. Telepathology appears to be following an S-curve for a technical innovation. PMID- 11774160 TI - Combined robotic and nonrobotic telepathology as an integral service component of a geographically dispersed laboratory network. AB - To achieve real-time connectivity between its 8 hopital-based laboratories, Veterans Integrated Service Network (VISN) 12, headquartered in Chicago, IL, has implemented a hybrid dynamic store-and-forward (HDSF) telepathology network that extends across portions of 3 states. The majority of diagnostic telepathology functions are provided to the 3 hospitals (Iron Mountain, MI; Tomah, WI; and North Chicago, IL), which lack on-site pathologists and are serviced by the 4 pathologists located in Milwaukee, WI. In surgical pathology, routine primary diagnosis, frozen section diagnosis, and clinical consultation are provided with telepathology. In addition, autopsy and specialty clinical conferences are frequently performed by using telepathology. Telepathology has been applied to a variety of areas within clinical pathology as well, including protein electrophoresis, immunoelectrophoresis, peripheral blood smears, body fluids, microbiology, and distance learning. Implementation of telepathology has allowed VISN 12 to reach the goal of providing a single standard of accurate and timely pathology service, even at small sites that lack an on-site pathologist. PMID- 11774161 TI - Online Internet-based robotic telepathology in the diagnosis of neuro-oncology cases: a teleneuropathology feasibility study. AB - This feasibility study examined the diagnostic accuracy of Internet-based dynamic robotic telepathology using neuropathology cases. Randomly, 83 cases were selected from the routine diagnostic workload of the Neurosurgical Pathology Laboratory in Poznan, Poland. Telepathology diagnoses were compared with conventional paraffin section diagnosis. The neuropathologists, operating a robotically controlled motorized microscope over the Internet from 3 different Polish cities, individually reviewed the cases using computer workstations. Viewing times ranged from 2 minutes 54 seconds to 32 minutes 12 seconds per case. The mean diagnostic accuracy for telepathology diagnosis was 95%, with 2 of 3 observers achieving 100% diagnostic accuracy. Image quality was judged to be sufficient for correct evaluation, and the viewing times required to establish a final diagnosis by remote video microscopy were acceptable. Generally, user acceptance of robotic telepathology was high. PMID- 11774162 TI - Clinical evaluation of an international static image-based telepathology service. AB - Telepathology is the use of telecommunications technology as a means to facilitate transfer of image-rich pathology data between remote locations for the purposes of diagnosis, education, and research. Although varying levels of technology exist to accomplish this task, static image--based systems are currently the most widely used around the world. Field selection and image quality have often been identified as major impediments to the successful use of static images for diagnostic telepathology. Between November 1994 and July 1999, the Armed Forces Institute of Pathology (AFIP) performed electronic consultation on over 1,250 static image--based cases, recording a clinically significant concordance rate of 97.3% between telepathology and final diagnosis (in cases in which follow-up material was available). For the same subset of cases, an absolute concordance rate of 73.7% was attained. A review of the case flow and construction of the AFIP telepathology system is presented, as well as factors that have an impact on the diagnostic accuracy of static image-based telepathology sytems in general. PMID- 11774163 TI - Telecytology: intraobserver and interobserver reproducibility in the diagnosis of cervical-vaginal smears. AB - Telecytologic diagnosis of cervical-vaginal smears is potentially useful because it could allow more efficient use of cytopathologist resources and expertise. A pathologist in one location could, in principle, review cytotechnologists' findings using a video display hundreds or thousands of miles away. Currently, bandwidth restrictions limit practical implementation of such a system to review of fields that had been selected for review by the cytotechnologist. The purpose of our investigation was to evaluate how well this type of review correlates with a review in which the entire slide is available for examination by the pathologist. We prospectively selected 100 consecutive cervical-vaginal smears over an 11-day period in August 1999. For each smear, 4 to 12 fields containing abnormal cells from each slide were digitally imaged. Each of 3 pathologists reviewed all digitized images and all glass slides. Diagnoses based on selected digitized images were compared with those based on conventional pathologist review. The kappa statistic, a measure of chance-corrected agreement (reproducibility), was calculated in each setting. Overall, intraobserver and interobserver reproducibility of cervical-vaginal smear diagnoses is fair to excellent. The use of remote digital images for pathologist review did not introduce large (2-step) diagnostic disagreements. The disagreement between a pathologist's glass slide and digital diagnoses is less than that for different pathologists reviewing glass slides, although interobserver differences were even greater in the interpretation of digital images. PMID- 11774164 TI - Characteristics of a telecytology consultation service. AB - Although numerous reports describe the application of remote video microscopy to pathologic diagnosis (telepathology), only a few address some of the special issues surrounding remote cytologic diagnosis (telecytology). These studies have generally suggested a high correlation between telecytologic diagnoses and those arising from direct examination of the glass slides, but factors affecting the clinical utility of routine cytologic diagnosis have not been examined. In this report, we describe our experience in telecytologic consultation on 99 cases seen at the Armed Forces Institute of Pathology between October 1995 and November 1999. The mean time between receipt of the telecytologic images and the contributor receipt of the faxed report was 9.9 hours (median, 5.13 hours). Using stringent criteria for agreement, we find fair to good (48%) concordance between the contributor's impression and the consultant's opinion. The concordance between the consultant's telecytologic diagnosis and the subsequent glass slide diagnosis is imperfect; in 8 (31%) of 26 cases in which the glass slide was sent after the telecytology consultation, a minor discrepancy between these diagnoses was found. No major discrepancies were found between the consultant's telecytologic and glass slide diagnoses. PMID- 11774165 TI - Telehematopathology in a clinical consultative practice. AB - We studied a series of 60 telepathology cases sent in consultation to the Department of Hematopathology from January 1, 1995, through July 31, 2000. Cases from the United States and the world representing academic, private, military, and federal sectors were reviewed. Ninety percent of patients were adults (54 of 60), and male patients outnumbered female patients 2 to 1. Ages were from 1 to 79 years (mean, 42 years). Forty-three cases were lymph nodes (72%), 14 were bone marrow or peripheral blood (23%), and 3 were from other sites (5%). Twenty-seven of the consultant diagnoses were benign (27 of 60). Twenty-nine were malignant (non-Hodgkin lymphoma, Hodgkin disease, and "other malignancy" groups), and 4 were nondiagnostic. Glass slide/paraffin tissue blocks were available in only 35 (58%) of 60 cases. The concordance rate for diagnostic telehematopathology cases with subsequent glass slide/paraffin block follow-up was 91% (29 of 32 cases). The discordance rate was 9% (3 of 32). This finding shows a high degree of diagnostic accuracy for consultative telehematopathology. Of 118 images analyzed, 58 were considered very good/good (49%), 32 were poor/very poor (27%), and 28 were fair (24%). Poor images had suboptimal resolution, color, or technical quality of transmission, and most poor images were low-power images. Additional case problems included insufficient immunoperoxidase stain availability, selection, and labeling; transmitted field selection; specimen preparation and staining; presence or absence of accompanying clinical data; and availability of ancillary studies such as flow cytometric, cytogenetic, and molecular data. From this analysis, the following recommendations are offered. To optimize telehematopathology consultation, include any additional information that have a significant influence on the final consultant diagnosis. Include any pertinent clinical information, laboratory data, special stains, immunoperoxidase stains, and molecular data. Select representative and diagnostically significant low power and high-power fields for an accurate diagnosis. Label every immunostain or special stain submitted. Always send glass slides and tissue blocks when requested by the consultant. Optimize telemedicine microscopy and computer equipment with appropriate technical expertise, training, and support. In conclusion, the field of telepathology offers an exciting and potentially powerful solution to the problem of national and global subspecialty consultation. Hematopathology is potentially well suited to this technologically advanced marriage of computer and Internet technologies with modern microscopy, molecular diagnostics, immunophenotypic profiling, and the consultant pathologist. PMID- 11774166 TI - Development and experience with an integrated system for transplantation telepathology. AB - Rapid and accurate interpretation of allograft biopsies influences the outcome after organ transplantation. Expert histopathologic interpretation can also determine whether a donor organ should be used for transplantation or disposed. These and similar considerations in the field of Transplantation Pathology prompted us to develop a static image, store-and-forward telepathology system capable of rendering accurate, robust, and confidential communication by using readily available equipment and bandwidth capabilities for interactive real-time second opinion consultation. Between July 1999 and October 2000, 102 cases were transmitted, including 78 for second opinion and 1 for primary diagnosis with 6 (5 real-time) frozen sections. Full agreement with the original diagnosis was obtained in 67 of 78 (86%) cases; in 11 (14%) cases, teleconsultation resulted in 8 minor and 3 clinically significant differences of opinion. This led to a change in therapy in 1 case and further evaluation in 2 other cases. We conclude that static image, store-and-forward telepathology can enhance the practice of transplantation pathology, but a multidisciplinary team for ongiong support and development is required. This technology has the potential to promote case sharing, conduct continuing education, build consensus, and standardize readings of biopsies in multicenter trials in which histopathologic findings represent important outcome measures. PMID- 11774167 TI - Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression. AB - The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER 2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation. PMID- 11774168 TI - Loss of cytokeratin 14 expression is related to human papillomavirus type and lesion grade in squamous intraepithelial lesions of the cervix. AB - In a recent study of low-grade cervical squamous intraepithelial lesions (SILs), we reported that infection with both low- and high-risk human papillomaviruses (HPVs) upregulated cyclin A, B, E, and Ki67 expression in basal and suprabasal cells. In view of the intricate link between cell cycle exit, proliferation, and differentiation, we examined the morphologic distribution of cytokeratins 13 and 14 and involucrin expression in 49 low-grade SILs infected with HPV types 6, 11, 16, 18, 31, 33, 39, 42, 43, 44, 45, 51, 52, 56, 58, and 66; 2 lesions contained both low- and high-risk HPVs. The findings were compared with 30 high-grade SILs infected with HPV types 16, 31, 33, 51, 58, 66, and 67; 3 of these were infected with 2 different HPVs. In low-grade lesions, the differentiation markers were expressed normally, showing that differentiation proceeds despite upregulation of cell cycle--associated proteins. Loss of involucrin (3 of 33) and cytokeratin 13 (8 of 33) expression occurred only in the high-grade lesions and was therefore related to lesion grade. Loss of cytokeratin 14 expression was also significantly more frequent in high-grade than in low-grade lesions (19 of 33 v 12 of 51; P < .01). In addition, cytokeratin 14 expression was significantly less frequent in the intermediate and superficial layers of low-grade SILs infected with high-risk HPVs than in those infected with low-risk HPVs (3 of 27 v 14 of 24; P < .001). These findings are consistent with in vitro data and suggest that abnormalities of both cell cycle control and squamous differentiation are important in HPV associated neoplastic transformation. PMID- 11774169 TI - Vitronectin in the cirrhotic liver: an immunomarker of mature fibrosis. AB - Vitronectin (Vn) is a multifunctional plasma glycoprotein produced by hepatocytes. Vn has been studied extensively as a cell adhesion molecule. However, its localization in the hepatic extracellular matrix has received relatively little attention. Cryosections of 5 normal liver samples and of 20 specimens showing posthepatitic cirrhosis were stained by the avidin-biotin complex method with a well-characterized monoclonal antibody to Vn. The extent and intensity of immunostaining were assessed semiquantitatively (0, no staining; 1+, weak focal staining; 2+, strong focal staining; 3+, strong diffuse staining). Paraffin sections from the same samples were stained with Masson trichrome (MT) and Shikata orcein (Or) methods. Frozen samples from selected cases were analyzed by Western blotting. In the normal liver, 3+ staining was limited to portal vessels. The portal tract connective tissue showed minimal staining (0 to 1+). Cirrhotic septa showed strong staining (2+). Septa lacking significant inflammation and composed of dense connective tissue, as indicated by MT and Or stains, showed the strongest Vn reactions (3+). Immunoblotting data strongly correlated with Vn increase in cirrhotic livers. Vn immunoreactivity is markedly increased in the cirrhotic liver matrix, regardless of the documented decrease in plasma Vn. Binding to collagen, elastin, and proteoglycans is the current favored mechanism of Vn deposition in tissues. Previous studies in cirrhotic patients showed increased affinity of plasma Vn to collagen. Vn is also increased in aged skin, associated with dermal elastic fibers. In other tissues, Vn deposition reflects chronicity of injury. Therefore, Vn immunoreactivity in liver can be considered a marker of fibrosis, especially of chronic/mature fibrosis, paralleling previous observations on enhanced orcein staining of cirrhotic septa. Immunolabeling of biopsy specimens with Vn and tenascin, a marker of ongoing remodeling or recently formed fibrous tissue, could be diagnostically helpful. PMID- 11774170 TI - High expression of CD34-positive sinusoidal endothelial cells is a risk factor for hepatocellular carcinoma in patients with HCV-associated chronic liver diseases. AB - CD34 has been widely used for the assessment of sinusoid-like neoangiogenesis in hepatocellular carcinoma (HCC). Recently, it was demonstrated that CD34-positive cells isolated from human peripheral blood differentiate into endothelial cells and contribute to neoangiogenesis in adults. We investigated the localization and the substantial role of CD34-positive endothelial cells in the liver with hepatitis C virus (HCV)--associated chronic liver diseases. Liver tissue sections obtained by biopsy from 56 patients with HCV-associated chronic liver diseases by were examined immunohistochemically using anti-CD34, anti-von Willebrand factor (vWF), and anti-vascular endothelial growth factor (VEGF) antibodies. CD34 was stained in the sinusoid, showing dotty, linear, semicircular, or circular patterns. However, sinusoidal expression of vWF was not substantially identified in the same specimens, indicating the existence of sinusoidal CD34-positive but vWF-negative endothelial cells. We classified these cells as CD34 LI and found that CD34 LI was correlated with the expression of VEGF. Among 34 patients with advanced-stage disease, the cumulative incidence of HCC was significantly higher in patients with CD34 LI >or= 12 (n = 16) than in those with CD34 LI < 12 (n = 18; P = .009). Moreover, among several clinicopathologic risk factors, CD34 LI could be recognized as an independently significant factor for development of HCC (relative risk, 7.36; P = .019). We conclude that CD34-positive endothelial cells are regulated by several factors, such as VEGF, and might play a substantial role in hepatocarcinogenesis. Furthermore, high expression of CD34-positive sinusoidal endothelial cells is a risk factor for HCC in patients with HCV-associated chronic liver diseases. PMID- 11774171 TI - Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver. AB - We studied the explanted livers from 12 patients with fulminant hepatic failure who were treated with a bioartificial liver and subsequently underwent orthotopic liver transplantation and from 18 patients who underwent orthotopic liver transplantation without previous treatment. Ten normal livers were used as controls. In addition to morphologic evaluation, an immunohistochemical analysis was performed with the monoclonal antibodies for alpha-smooth muscle actin and proliferation marker Ki-67. The expression of these markers was graded semiquantitatively from 0 to 3+ in a blinded fashion. The zonal distribution of activated hepatic stellate cells was also evaluated. In all cases, the hepatic stellate cells were activated and expressed alpha-smooth muscle actin. In all patients with submassive or massive liver cell necrosis, the distribution of activated hepatic stellate cells was predominantly in zone 1 of the acinus (periportal area). In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus. Expression of the proliferation marker Ki-67 was graded 3+ in all patients treated with the bioartificial liver who had orthotopic liver transplantation and 2+ in patients who underwent orthotopic liver transplantation only. PMID- 11774172 TI - High proliferative activity may predict early metastasis of thin melanomas. AB - Metastasis of thin melanomas is uncommon and unpredictable. We prospectively investigated the clinical course of 167 thin melanomas (<1 mm thickness) over a median observation period of 4 years (18 to 87 months). In addition to Breslow thickness, Clark level, and growth phase characteristics, we assessed cellular proliferation by counting mitoses and immunohistochemically using the monoclonal antibody Ki-S5 (Ki-67). Mitotic and Ki-S5 indices were correlated to tumor thickness, Clarks level, and radial/vertical growth phase (RGP/VGP). However, 5 tumors had proliferation indices above 25% (outside the range of a theoretical normal distribution). Four of these tumors metastasized, and none of the melanomas with lower proliferative activity progressed during the observation period. The metastatic behavior was independent of tumor thickness and Clark level and did not unconditionally coincide with VGP or high mitotic counts. It is concluded that the immunohistochemical proliferation index may be a powerful predictor of early systemic progression in thin melanomas, which may be helpful in making therapeutic decisions. Further investigations are needed to determine the value of proliferation measurements for the long-term prognosis of thin melanomas. PMID- 11774173 TI - Inflammatory pseudotumor of lymph node and spleen: an entity biologically distinct from inflammatory myofibroblastic tumor. AB - Inflammatory pseudotumors (IPTs) of the lymph node and spleen are an uncommon, benign cause of lymphadenopathy and/or splenomegaly that often bear striking clinicopathologic similarities to the inflammatory myofibroblastic tumors (IMTs) found in soft tissues. These tumors have classically been grouped together under the umbrella category of "inflammatory pseudotumor." Recent evidence shows that IMTs are in fact neoplastic processes that often harbor balanced chromosomal translocations involving the ALK kinase gene. These translocations result in expression of ALK kinase in IMTs as assessed by immunohistochemical studies. However, the relationship between IMT and IPT of the lymph node and spleen is uncertain. To determine if ALK tyrosine kinase expression is also present in IPT, 13 cases of IPT (9 involving lymph nodes, 4 splenic lesions) were examined for the presence of ALK tyrosine kinase by immunohistochemical staining on paraffin embedded tissue. In addition, in situ hybridization studies for Epstein-Barr virus--encoded RNAs (EBER) and immunoperoxidase studies for human herpesvirus-8 (HHV8)--specific proteins were performed. All cases had clinical, morphologic, and immunophenotypic findings typical of IPT and had varying proportions of fibroblastic and inflammatory components. Age ranged from 11 to 75 (median, 40) years; 8 subjects were male, and 5 were female. None of the cases (0 of 13) had positive staining for ALK kinase or HHV8, and in 1 a lymph node (1 of 13) was focally positive for EBV (EBER) by in situ hybridization. The absence of ALK kinase as detected by immunohistochemical studies in IPT of the lymph node and spleen suggests that this entity is biologically distinct from the histologically similar IMT. PMID- 11774174 TI - Arcuate and interlobular phlebitis in renal allografts. AB - Intimal arteritis in the renal allograft has a well-documented adverse effect on graft outcome. In contrast, venulitis is currently considered an innocuous finding, based largely on observations of thin-walled intermediary venules. Arcuate and interlobular veins have not been studied specifically. These veins have well-developed muscular walls, and inflammation at this level (phlebitis) could significantly alter renal hemodynamics. We studied the clinicopathologic correlates of arcuate and interlobular phlebitis in 31 renal allograft biopsy specimens. Phlebitis was seen in conjunction with borderline changes suggestive of acute cellular rejection (13 cases), or acute rejection Banff grade 1A (7 cases), Banff grade 1B (6 cases), Banff grade 2A (4 cases), and Banff grade 2B (1 case). Clinical follow-up (average 323 +/- 460 days) showed no adverse effects of phlebitis as judged by temporal changes in serum creatinine and the grade of chronic allograft nephropathy in follow-up biopsies. Thus it appears that arcuate and interlobular phlebitis in allograft biopsy specimens does not add prognostic information beyond that provided by conventional Banff criteria. However, this lesion frequently coexists with changes suggestive or diagnostic of acute cellular rejection, and intimal arteritis may be seen concurrently in up to 16% of cases. PMID- 11774175 TI - Aneusomy of chromosomes 7, 8, and 17 and amplification of HER-2/neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma: a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray. AB - Recent evidence shows that the proportion of poorly differentiated prostate carcinoma (Gleason pattern [GP] 4/5) is a surrogate factor for biochemical failure after radical prostatectomy (RP). However, little is known about specific molecular and cytogenetic changes in this aggressive component of localized prostate cancer. We constructed a tissue microarray containing areas of GP 3 and 4 from formalin-fixed radical prostatectomy specimens of 39 patients with Gleason score 7 carcinoma (>or=50% GP 4), known pathologic staging parameters (stage < T3b), and biochemical failure data (mean follow-up, 30 months; range, 5 to 74 months). Interphase fluorescent in situ hybridization (FISH) was performed on 5 microm microarray sections using pericentromeric probes to chromosomes 7, 8, and 17 and probes for the HER-2/neu and epidermal growth factor receptor (EGFR) genes. Low-level amplification of HER-2/neu was found in 26% of cases (3 to 5 signals per nucleus, corrected for chromosome 17 aneusomy). Aneusomy of chromosomes 7, 8, and 17 was identified in 21%, 15%, and 5% of cases, respectively. All aberrations occurred almost exclusively in GP 4 carcinoma (8 of 8 aneusomies 7, 2 of 2 trisomies 17, 9 of 10 HER-2/neu amplifications, and 5 of 6 aneusomies 8; P < .001). The presence of HER-2/neu amplification was associated with high tumor volume (>2.0 cm(3), P = 0.004). Among patients with negative surgical margins, gain of chromosome 7 was associated with biochemical failure after RP (P =.004, log-rank). Amplification of the EGFR gene occurred in only 1 case (3%). Significant differences in HER-2/neu amplification and gain of chromosomes 7, 8, and 17 were detected between GP 4 prostate carcinoma and GP 3. The frequency of aberrations increased with tumor volume. Chromosome 7 abnormalities may play an important role in cancer progression in margin-negative patients. EGFR amplification was rare, suggesting that this oncogene is not altered at the gene copy number level. PMID- 11774176 TI - Diffuse alveolar damage and recurrent respiratory failure: report of 6 cases. AB - We report 6 patients in whom diffuse alveolar damage (DAD) was found on 1 or more lung biopsy specimens and who experienced recurrent episodes of acute respiratory failure. The patients ranged in age from 43 to 55 years. Two to five episodes of respiratory failure occurred in each over a period of 4 months to 2 years. One patient developed evidence of chronic lung disease; while the others remained well between episodes. Lung biopsies showed the acute stage of DAD in 3, overlapping acute and organizing stages in 3, and the organizing stage in 2. A definite cause was not identifiable in any. However, 4 had been treated with narcotics for chronic pain before the first episode, and 1 received this treatment before the recurrent episode. Three also were receiving psychotropic drugs for anxiety and depression. Five patients had evidence of gastroesophageal reflux disease (GERD) and/or hiatal hernia, 2 of whom underwent Nissen fundoplication in hopes of preventing future recurrences. Although a definite cause of the recurrent DAD was not identified, the findings suggest the possibility of a reaction to narcotics and/or psychotropic drugs in some patients, with a possible additional effect of GERD. A drug history should be carefully elicited in patients with recurrent DAD, and all potentially toxic drugs should be stopped. PMID- 11774177 TI - Dedifferentiation of adenoid cystic carcinoma: report of a case implicating p53 gene mutation. AB - Adenoid cystic carcinoma is an indolent tumour with an unfavorable long-term prognosis. Dedifferentiation of adenoid cystic carcinoma, which is associated with an accelerated clinical course, has recently been described. We report a case with immunohistochemical and molecular workup to elucidate the likely mechanism of dedifferentiation. The patient, a 64-year-old woman, developed dedifferentiated adenoid cystic carcinoma of the submandibular gland ab initio, accompanied by cervical lymph node metastasis. Histologically, the low-grade adenoid cystic carcinoma merged gradually into an extensive dedifferentiated component that was composed of solid sheets and cords of anaplastic tumor cells with focal gland formation. Immunohistochemically, the dedifferentiated component, but not the adenoid cyst carcinoma component, showed strong overexpression of p53 protein and cyclin D1, as well as a higher Ki67 index. Molecular study confirmed the presence of p53 gene mutation selectively in the dedifferentiated component, suggesting a pivotal role of p53 gene alteration in the dedifferentiation process of adenoid cystic carcinoma. PMID- 11774178 TI - Sudden infant death caused by a ruptured coronary aneurysm during acute phase of atypical Kawasaki disease. AB - This article describe's a case of atypical Kawasaki disease (AKD) with lack of typical clinical signs and rapid fatal course in a 2-month-old infant, who 1 week before hospitalization demonstrated rhinitis, coughing without fever, and later conjunctival hyperemia and allergic exanthema on chest and arms. On admittance, labwork highlighted the following: leukocytosis, thrombocytosis, elevated sedimentation rate, and positive C-reactive protein. General conditions remained mediocre for 7 days until sudden death occurred. The autopsy confirmed death caused by cardiac tamponade caused by a ruptured inflammated aneurysm of the left anterior descending coronary artery. We believe that the currently accepted clinical diagnostics criteria for KD in infants 2 years of age or younger can cause missed in vita diagnosis of AKD. For such, any typical clinical sign of KD whenever associated with thrombocytosis and elevated indices of phlogosis, should led to suspicion of KD and permit cardiovascular examination, and thus early treatment. PMID- 11774180 TI - Are PCR artifacts in microdissected samples preventable? PMID- 11774179 TI - Monoclonal proliferation of germinal center cells (incipient follicular lymphoma) in an axillary lymph node of a melanoma patient. AB - A monoclonal proliferation of germinal center cells within a lymph node follicle was incidentally discovered during the staging surgical procedures in a patient with Clark III-level cutaneous melanoma. In one of the 19 axillary lymph nodes examined, we identified a single morphologically atypical lymphoid follicle, predominantly composed of medium-sized cells and immunoreactive for B-cell antigens and for the markers of germinal center origin CD10 and bcl-6. A monoclonal rearrangement of the immunoglobulins heavy chains (IgH) was documented by polymerase chain reaction after laser capture microdissection. The cells of the aberrant follicle expressed the bcl-2 protein at higher levels than the surrounding T lymphocytes in the absence of bcl-2 gene rearrangement. We propose for this lesion the designation of incipient follicular lymphoma. The present findings also confirm the previously reported association between melanoma and lymphoproliferative disorders. PMID- 11774185 TI - Molecular genetic pathology: an exam, finally. PMID- 11774182 TI - Tumor invasion and metastasis--nature or nurture? PMID- 11774186 TI - Reproducible gene expression measurement among multiple laboratories obtained in a blinded study using standardized RT (StaRT)-PCR. AB - BACKGROUND: A method that provides standardized data and is relatively inexpensive and capable of high throughput is a prerequisite to the development of a meaningful gene expression database suitable for conducting multi institutional clinical studies based on expression measurement. Standardized RT (StaRT)-PCR has all these characteristics. In addition, the method must be reproducible. StaRT-PCR has high intralaboratory reproducibility. The purpose of this study is to determine whether StaRT-PCR provides similar interlaboratory reproducibility. METHODS AND RESULTS: In a blinded interlaboratory study, expression of ten genes was measured by StaRT-PCR in a complementary DNA sample provided to each of four laboratories. The average coefficient of variation for interlaboratory comparison of the nine quantifiable genes was 0.48. In all laboratories, expression of one of the genes was too low to be measured. CONCLUSION: Because StaRT-PCR data are standardized and numerical and the method is reproducible among multiple laboratories, it will allow development of a meaningful gene expression database. PMID- 11774187 TI - Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens. AB - BACKGROUND: Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene. METHODS AND RESULTS: We investigated the utility of HFE gene sequence analysis in the diagnosis of HH in 61 prospectively accrued formalin-fixed, paraffin-embedded liver biopsy specimens with clinical or histologic features suggestive of HH. Mutations in codons 63 or 282 of the HFE gene were identified by direct sequencing; in 21 of these samples, quantitative hepatic iron testing was also performed. Changes characteristic of HH were present in 16 (26%) of the cases, and 54% of the cases showed HFE gene mutations. The most common alteration was homozygous mutation of codon 282 (11 cases, 18%), followed by the combined 63 + 282 heterozygous mutation (3 cases, 5%). Two cases (3%) showed biallelic mutation of codon 63. The other 28 cases (46%) showed no sequence abnormalities. Weak iron staining did not exclude HH; intense staining did not reliably predict HH. CONCLUSION: When HH is clinically and/or histologically suspected, HFE gene sequencing of formalin-fixed, paraffin embedded liver biopsy specimens is a rapid and cost-effective approach to genotypic diagnosis of HH. PMID- 11774188 TI - Differential detection of cytomegalovirus immediate-early messenger RNA in clinical samples using ligation-dependent PCR. AB - BACKGROUND: Cytomegalovirus (CMV) causes life-threatening infections in immunocompromised patients, especially those with acquired immunodeficiency or organ transplants. Therefore, early detection of CMV is important to guide the clinical management of actively infected patients. Because detection of replicative transcripts indicates that the virus is in the process of being replicated in the infected cell, we applied a novel, sensitive, ligation dependent (LD)-PCR method to detect CMV immediate-early (IE) messenger RNA (mRNA), an indicator of viral replication. METHODS AND RESULTS: Viral mRNAs were released from infected cells by incubation in 5 M guanidinium thiocyanate, and IE mRNAs were captured onto magnetic beads through oligo(dT) capture probes. Two hemiprobes, each containing an IE mRNA-complementary region and a region for PCR primer binding, were captured by binding to the IE mRNA. These hemiprobes, bound on an IE mRNA in juxtaposition to one another, were linked together by a DNA ligase to form a full probe that served as the template for PCR amplification. This approach detected IE mRNAs in CMV-propagating cells, but not in supernatants containing only viral DNAs. Thirty-one clinical specimens were tested by LD-PCR; 18 specimens were positive (ten specimens, bronchoalveolar lavage [BAL]; five specimens, urine; two specimens, blood; one specimen, biopsy), 17 of which were confirmed by culture. Three culture-positive samples (two specimens, urine; one specimen, BAL) were missed by LD-PCR, and one urine sample was positive by LD-PCR but negative by culture. CONCLUSION: LD-PCR assay is a reliable test for the early diagnosis of active CMV infection in patient specimens. PMID- 11774190 TI - Microbial disease in humans: A genomic perspective. AB - The approach of whole-genome shotgun sequencing coupled with the availability of computational algorithms to facilitate the assembly, gene prediction, and functional annotation of entire genomes has sparked a revolution in our understanding of the biology of free-living organisms. More than 40 bacterial genomes have been sequenced to date, of which several are important human pathogens. The capacity to sequence and assemble entire genomes of bacteria, pathogenic protozoans, and fungi in a rapid and cost-effective way has energized every aspect of microbial science. Comparative genome analysis allows us to dissect the evolutionary forces at work and provides insights into adaptations of microbes to their unique ecological niches. Factors that shape host-pathogen interactions and their outcomes include genetic polymorphisms in the microbial pathogen and host, both of which can impact on microbial virulence or host immune responses to infection. The availability of the genome sequence of entire organisms, together with the use of high-throughput sequence-based genomic technologies to define microbial and host physiological states, provides the unparalleled opportunity to better define clinical outcomes in the field of infectious diseases. There is one overarching lesson: completion of the genomic sequence of any species answers many questions, while at the same time it invites totally new questions. PMID- 11774191 TI - Testing for HIV-1 drug resistance. AB - Viral resistance to antiretroviral agents may limit the efficacy of current treatment regimens for HIV-1 infection. The mutational patterns underlying resistance to each antiretroviral agent are often quite diverse, and cross resistance patterns in each of the currently available classes are complex. Current methods for determining drug resistance include genotypic and phenotypic assays, and each has advantages and limitations. Prospective clinical trials assessing the utility of HIV-1 drug resistance testing have shown significant but modest improvement in virologic outcomes with genotypic assays. Some, but not all, trials of phenotypic resistance testing have demonstrated improved virologic outcomes. Resistance testing is currently recommended for patients who have virologic failure or have no response to an antiretroviral regimen, and for pregnant women. Testing should also be considered in treatment-naive patients in areas of high prevalence of transmitted drug-resistant virus. PMID- 11774192 TI - Hepatitis C virus genotyping: clinical implications and methods. AB - Hepatitis C virus (HCV) chronically infects at least 1% of the world's population and is a leading cause of end-stage liver disease. HCV displays a remarkable degree of genomic diversity, with the six major genotypes and numerous subtypes differing in geographic distribution. The ability of this virus to cause persistent infections is a direct result of its genomic plasticity and the evolution of quasispecies within an infected individual. HCV genotype has emerged as an important factor both in predicting a sustained response to, and in determining the duration of, antiviral therapy. Although a variety of methods have been used for genotyping HCV, nucleotide sequencing of a phylogenetically informative region remains the gold standard. PMID- 11774193 TI - Epstein-Barr viral load measurement as a marker of EBV-related disease. AB - Epstein-Barr virus (EBV) is associated with a wide variety of benign and neoplastic diseases. EBV viral load assays that may prove useful in rapid assessment of disease status are now available. The two most common approaches to viral load measurement are quantitative, competitive PCR, and real-time PCR. Laboratory studies have shown that these assays are sensitive and specific for measuring EBV DNA in blood samples. Clinical investigations suggest a role for viral load measurement in predicting and monitoring EBV-associated tumors, including nasopharyngeal carcinoma, post-transplant lymphoproliferative disorder, Hodgkin's disease, and AIDS-related lymphoma. These new laboratory tools show promise in improving clinical management of affected patients. PMID- 11774194 TI - Diagnosis of influenza virus: coming to grips with the molecular era. AB - Influenza viruses continually circulate and cause yearly epidemics, which kill 20,000 people in an average year in the United States. Occasionally and unpredictably, pandemic influenza strains sweep the world, infecting 20% to 40% of the world's population in a single year. In 1918, the worst influenza pandemic on record caused 675,000 deaths in the United States and up to 40 million deaths worldwide. Despite the prevalence of this virus, molecular assays for influenza diagnosis, surveillance, vaccine strain selection, and research have lagged behind such assays for other common viral pathogens. The extreme genetic variability of influenza viruses makes the design of useful molecular-based assays challenging, but several different approaches have been successfully used. RT-PCR is effective for the initial diagnosis and has greater sensitivity than other available rapid assays. Molecular assays also can be used to subtype influenza isolates, and sequence analysis of hemagglutinin may assist greatly in surveillance studies and vaccine strain selection. RT-PCR for influenza also can be performed from tissue biopsy specimens for both retrospective diagnosis and research. PMID- 11774195 TI - Diagnosing human parvovirus B19 infection: guidelines for test selection. AB - Human parvovirus B19 is the cause of a common childhood disease that usually has a mild and self-limited course. Complete viral replication and subsequent cell lysis are limited to early erythroid precursor cells expressing the globoside receptor. Individuals with shortened red blood cell half-lives and immunocompromised or immunosuppressed patients, as well as pregnant women and developing fetuses, are at risk for severe anemia and/or persistent infection from human parvovirus B19. Selection of the diagnostic test(s) to use to detect parvovirus B19 is patient dependent. Serological testing is most appropriate in immunocompetent individuals, including children and pregnant women, who have symptoms consistent with parvovirus B19 infection or a history of recent exposure. Conversely, a molecular amplification assay should be chosen to detect parvovirus B19 DNA in individuals lacking an adequate antibody-mediated immune response. In summary, it is critical that clinicians are educated about the most appropriate diagnostic test to detect parvovirus B19 infection in their patients because selecting an inappropriate or inaccurate test for parvovirus B19 can lead to misinformation and/or misdiagnosis. PMID- 11774197 TI - Biological agents: weapons of warfare and bioterrorism. AB - The use of microorganisms as agents of biological warfare is considered inevitable for several reasons, including ease of production and dispersion, delayed onset, ability to cause high rates of morbidity and mortality, and difficulty in diagnosis. Biological agents that have been identified as posing the greatest threat are variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum toxin (botulism), Francisella tularensis (tularaemia), filoviruses (Ebola hemorrrhagic fever and Marburg hemorrhagic fever), and arenaviruses Lassa (Lassa fever) and Junin (Argentine hemorrhagic fever). The pathogenesis, clinical manifestations, diagnosis, and treatment of these agents are discussed. Rapid identification and diagnosis using molecular diagnostic techniques such as PCR is an essential element in the establishment of coordinated laboratory response systems and is the focus of current research and development. Molecular techniques for detection and identification of these organisms are reviewed. PMID- 11774196 TI - 16S rRNA gene sequencing for bacterial pathogen identification in the clinical laboratory. AB - For many years, sequencing of the 16S ribosomal RNA (rRNA) gene has served as an important tool for determining phylogenetic relationships between bacteria. The features of this molecular target that make it a useful phylogenetic tool also make it useful for bacterial detection and identification in the clinical laboratory. Sequence analysis of the 16S rRNA gene is a powerful mechanism for identifying new pathogens in patients with suspected bacterial disease, and more recently this technology is being applied in the clinical laboratory for routine identification of bacterial isolates. Several studies have shown that sequence identification is useful for slow-growing, unusual, and fastidious bacteria as well as for bacteria that are poorly differentiated by conventional methods. The technical resources necessary for sequence identification are significant. This method requires reagents and instrumentation for amplification and sequencing, a database of known sequences, and software for sequence editing and database comparison. Commercial reagents are available, and laboratory-developed assays for amplification and sequencing have been reported. Likewise, there are an increasing number of commercial and public databases. Despite the availability of resources, sequence-based identification is still relatively expensive. The cost is significantly reduced only by the introduction of more automated methods. As the cost decreases, this technology is likely to be more widely applied in the clinical setting. PMID- 11774198 TI - Using standards and controls in molecular assays for infectious diseases. AB - Ten years ago, laboratory directors introducing molecular infectious disease diagnostics in the routine clinical setting had few resources to assist in their implementation and quality assurance programs. In the past 10 years, several organizations have recognized this need and have established standard reference materials, controls, external quality assessment programs, and written guidelines. It is a challenge for the clinical laboratory scientist to evaluate and incorporate these new programs and services in the context of traditional good laboratory practice and current laboratory regulations. This article presents many of the options available for control materials, proficiency programs, standard reference materials, and written guidelines. It shows where harmonization of new practice with long-standing convention and regulation is progressing and where questions remain. PMID- 11774199 TI - Hemochromatosis caused by mutations in the iron-regulatory proteins ferroportin and H ferritin. PMID- 11774200 TI - An overview of HER2. AB - HER2 is a transmembrane growth factor receptor found in normal and malignant breast epithelial cells. Phosphorylation of the intracellular tyrosine kinase results in intracellular signaling and activation of genes involved in cell growth. Overexpression of HER2 has independent prognostic significance in early breast cancer and may also predict response to hormonal and cytotoxic therapies, although this latter role is less well studied. Prospective stratification of HER2 status in current clinical trials may more accurately delineate these roles. Anti-HER2 therapy, using a humanized monoclonal antibody, has enhanced survival when given with chemotherapy compared with chemotherapy alone in patients with metastatic HER2-overexpressing breast cancer. A potential limitation to its use in the adjuvant setting is the increased incidence of cardiotoxicity in patients treated either concurrently or previously with anthracyclines; carefully designed prospective adjuvant trials are currently being launched. HER2 is a relatively new prognostic marker and holds promise for predicting response to various therapies and for target-specific therapy. PMID- 11774201 TI - Cancer vaccines targeting the HER2/neu oncogenic protein. AB - Several advances in basic immunology over the last few years have forced a re evaluation of cancer vaccine development. The most important finding has been that human tumors are immunogenic. The HER2/neu oncogenic protein is a tumor antigen. Existent antibody, helper T-cell, and cytotoxic T-cell immunity to HER2/neu have been detected in patients with cancer. The HER2/neu protein is an excellent therapeutic target for the immune system. Passive immunotherapy strategies, such as the infusion of monoclonal antibodies specific for HER2/neu, have been shown to be of clinical benefit in patients with HER2/neu overexpressing malignancies. Inducing an active immune response by generating endogenous HER2/neu-specific antibodies and T cells may result in long-lived immunity and, hopefully, therapeutic benefit. In the majority of patients with pre-existent HER2/neu immunity, the antigen-specific antibodies and T cells detected are of low magnitude. Therefore, vaccine strategies aimed at boosting immunity already present may be effective in generating significant levels of HER2/neu-specific antibodies and T cells. PMID- 11774202 TI - Targeting HER2: recent developments and future directions for breast cancer patients. AB - Overexpression of the HER2/neu oncogene (also known as c-erbB2) is a frequent molecular event in multiple human cancers, including breast and ovarian cancer. Patients with cancer that overexpress HER2/neu are associated with unfavorable prognosis, shorter relapse time, and low survival rate. Treatments that target HER2/neu expression in cancer cells have been shown to be useful strategies to significantly reverse the malignancy induced by HER2/neu overexpression. The humanized anti-HER2/neu antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) has proven to be effective in clinical trials in patients with metastatic breast cancer. In addition, tyrosine kinase inhibitors such as emodin can also target the HER2/neu oncogenic activity. Emodin treatment inhibits HER2/neu tyrosine kinase activity and preferentially suppresses the transformation of HER2/neu-overexpressing breast cancer cells. Emodin also sensitizes HER2/neu-overexpressing cancer cells to chemotherapeutic agents, including cisplatin, doxorubicin, etoposide, and paclitaxel. Alternatively, HER2/neu overexpression can be repressed by attenuating the promoter activity of the HER2/neu gene. We have identified a number of potent transcriptional regulators, including the ets family member PEA3 and the adenovirus type 5 E1A, which are able to repress HER2/neu gene expression. Expression of these transcriptional regulators resulted in downregulation of HER2/neu promoter activity and reversed the transformed phenotype of the cancer cells in vitro. In vivo studies show that these HER2/neu repressors can act therapeutically as tumor suppressor genes for tumors that overexpress HER2/neu. These preclinical studies clearly indicate that transcriptional repressors that downregulate HER2/neu can be effective regimens for cancer treatment in a gene therapy format. More importantly, the tumor-free survival rate of treated animals is dramatically increased under nontoxic doses compared with untreated animals. A phase I clinical trial using E1A-liposome in breast and ovarian patients has recently been completed. Following treatment, we observed downregulation of the HER2/neu protein accompanied by E1A expression in both cancer and noncancer cells. Numbers of tumor cells in the pleural effusion or ascites were found to be dramatically reduced after treatment. Furthermore, apoptosis was strongly induced in the tumor cells. A phase II study has been started to further evaluate therapeutic efficacy and tumor suppression mechanisms of E1A. These studies show the clinical potential of targeting HER2/neu in cancer therapy. PMID- 11774203 TI - Inhibitors of HER2/neu (erbB-2) signal transduction. AB - Signaling by the HER2 proto-oncogene product results in the activation of several biochemical pathways that in turn modulate the expression and function of molecules involved in cell proliferation and survival. It is well established that forced overexpression of HER2 results in transformation of nontumor cells, and that high levels of HER2 in tumors are associated with a more aggressive biological behavior. It is also clear that a subset of HER2-overexpressing tumors is dependent on HER2 function for proliferation and/or survival. Over the last few years, several elegant studies have dissected the biochemical mechanisms of HER2 signaling. This research has provided information about critical functional domains in HER2 that can be targeted with rational molecular approaches, some of which are already being implemented at the bedside. This report will focus on one of these anti-HER2 signaling strategies. PMID- 11774204 TI - Structural requirements for ErbB2 transactivation. AB - ErbB2 is a unique member of the ErbB family of receptor tyrosine kinases that is distinguished by the fact that no ligand has yet been identified. Due to the absence of an ErbB2 ligand, alternative mechanisms are used for ErbB2 activation. As such, when ErbB2 is overexpressed, kinase activation occurs in the absence of ligand because of constitutive homodimerization. However, at normal expression levels ErbB2 acts as the shared coreceptor for the ErbB family, and these heterodimeric complexes are activated in response to the partner ligand. While the extracellular domain and transmembrane domains are necessary for ErbB2 transactivation, the carboxy terminus is also required. Specifically, ligand dependent ErbB2 transactivation requires a discrete three-amino-acid segment, located at the C-terminus of ErbB family members ErbB3, ErbB4, and the epidermal growth factor receptor. Transactivation of ErbB2 via the three-amino-acid segment likely represents a conserved mechanism for regulated signaling by the ErbB family of receptors. PMID- 11774205 TI - Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. AB - HER2/neu amplification/overexpression confers more aggressive and malignant characteristics on breast cancer cells. Patients with HER2/neu-amplified breast cancer have a worse prognosis than those with normal HER2/neu expression. Over the past decade, the intracellular signaling pathways associated with this growth factor receptor have been elucidated. Multiple therapeutic strategies that target the HER2/neu oncoprotein are under development. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA), a humanized monoclonal antibody that binds to the extracellular domain of the HER2/neu receptor, has undergone phase I, II, and III clinical trials. These studies have shown that, as a single agent, trastuzumab has substantial and reproducible antitumor activity in HER2/neu amplified metastatic breast cancer. In addition, when added to chemotherapy, trastuzumab improves antitumor efficacy as measured by time to progression, response rate, and survival. Additional chemotherapy/trastuzumab combinations are under active evaluation, and new schedules of administration are being tested. Thus, trastuzumab is the first successful example of molecularly targeted therapy in the management of metastatic breast cancer. PMID- 11774206 TI - [Sequence analysis of mtDNA 12S rRNA, tRNA(Leu(UUR)),tRNA(Ser(UCN))and 16S rRNA gene of 12 nonsyndromic inherited deafness pedigrees]. AB - OBJECTIVE: To detect the relationship of mtDNA mutation with inherited deafness and the reason for pedigree's hypersensitivity to ototoxicity of aminoglycoside antibiotics(AmAn). METHODS: Pedigree investigations were conducted. The blood samples were obtained from 12 pedigrees, and DNA was extracted from the isolated leukocytes. After that, mtDNA fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutations were detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion respectively, and then sequencing of 12S rRNA, tRNA(Leu(UUR)), tRNA(Ser(UCN))and 16S rRNA gene was performed. RESULTS: Restriction endonuclease digestion and sequence analysis showed that all the pedigrees carried mtDNA mutation, among them, 10 pedigrees carried 1555(G) mutation; 2 pedigrees, 7445(G) mutation; no pedigree was found to harbor the 3243(G) mutation. Sequence analysis of 16S rRNA gene showed that the mutations are 2230(G), 2230(AG), 2243(AG), 2230(AA). CONCLUSION: The pedigrees that carried 1555(G) or 7445(G) mutation showed hereditary or congenital hearing loss. The 1555(G) or 7445(G) mutation in association with 16S rRNA gene mutation led to pedigree's hypersensitivity to AmAn ototoxicity. PMID- 11774207 TI - [Use of microsatellites in zygosity diagnosis of twins]. AB - OBJECTIVE: To diagnose zygosity of twins by microsatellite polymorphism. METHODS: One hundred and eighty-four samples, including 69 pairs of twins with the same gender and 6 pairs of twins with different gender were recruited. Seventeen sib pairs were also collected for controls. Nine highly polymorphic microsatellite loci were amplified by polymerase chain reaction (PCR) using fluorescence-labeled primers and the products were sized by automated fragment analysis after electrophoresis and laser detection. Zygosity was diagnosed by comparing the concordance of the genotype of the 9 markers. RESULTS: Sixty-three pairs of monozygotic (MZ) and 12 pairs of dizygotic (DZ) twins were assigned their zygosity by comparison of polymorphism of 9 microsatellite loci. Within each of the 63 monozygotic (MZ) pairs there was complete concordance. However, within each of the 12 dizygotic pairs and other 17 sib pairs, discordant loci were found. With five or six markers, the probability that any twin pair was MZ if all markers were concordant was 99% or 99.6%, respectively. With all the nine markers, the probability that any twin pair was MZ if all markers were concordant was 99.95%. CONCLUSION: The technology of gene scan and genotyping provides a rapid and reliable approach to zygosity detection. PMID- 11774208 TI - [The impact of calpain-10 gene combined-SNP variation on type 2 diabetes mellitus and its related metabolic traits]. AB - OBJECTIVE: To investigate the impact of calpain-10 gene (CAPN-10) combined single nucleotide polymorphism (SNP) variation on type 2 diabetes mellitus (T2DM) and its related clinical metabolic traits in Chinese. METHODS: The study population consisted of 268 Chinese residents in Shanghai. Among them, 144 were subjects with normal glucose tolerance (NGT) and 124, with T2DM. Plasma glucose (PG), insulin (INS), c-peptide (CP) and free fatty acids (FFA) levels were measured at fasting and 30, 60, 120, and 180 minutes after oral 75 g glucose challenge. The islet beta-cell insulin secretion and tissue insulin sensitivity were assessed. CAPN-10 UCSNP44,-43,-19 and -63 were genotyped. RESULTS: (1) In Chinese NGT subjects, the major allele of UCSNP-44 was allele T (frequency=91%), of UCSNP43 was G(89%), of UCSNP-19 was I (3 repeats of a 32 bp sequence) (67%) and of UCSNP 63 was C allele (79%). Significant differences were observed in comparison of these allele frequencies in Chinese to those in other ethnic groups reported in the literature. (2) 14 genotype combinations of these four SNPs were observed in Chinese NGT subjects. 69% of the NGT population was composed of four genotype combinations, in the order of UCSNP44,-43,-19 and -63, i.e., combination A:TT-GG DI-CC(haplotype combination was 1121/1111) (frequency=10%), combination B:TT-GA II-CC(1121/1221)(10%), combination C:TT-GG-II-CC(1121/1121)(26%) and combination D:TT-GG-DI-CT(1121/1112)(22%).(3) The frequencies of the above mentioned SNP in single or in combinations were not different significantly between NGT and T2DM groups. (4) The variation of clinical metabolic parameter levels shifted from completely normal towards abnormal glucose intolerance among genotype combination subgroups. In comparison between combination A and combination D, subjects in the former subgroups had: higher PG levels with delayed peak after glucose challenge; less and lower decrement of FFA levels after challenge with no rising in late stage; higher insulin levels with delayed peak after challenge; and the tendency of decreased insulin sensitivity. More than half of the comparisons remained statistically significant after adjusted with age, gender, body mass index and waist circumference. CONCLUSION: The variation of calpain-10 gene has impact on the variation of clinical metabolic parameter levels related to type 2 diabetes mellitus. Such impact depends upon the haplotypes as well as the haplotype combination of calpain-10 gene variations. PMID- 11774209 TI - [Association between dopamine transporter gene polymorphism and Parkinson's disease]. AB - OBJECTIVE: To detect the association between dopamine transporter gene polymorphism and Parkinson's disease (PD). METHODS: The authors analyzed the difference in the distribution of the variable number tandem repeat (VNTR ) polymorphism within the 3' untranslated region of the DAT gene between 85 normal controls and 128 PD patients that were further divided into the senile subgroup (aged >50 years at onset of PD ) and the early-onset subgroup (aged C(Val42Val) single nucleotide polymorphism(SNP) by sequencing. CONCLUSION: The 352 insA mutation is a new causative mutation and the 347A-->C is a rare single nucleotide polymorphism. PMID- 11774215 TI - [The polymorphism of (CAG)n repeats within androgen receptor gene among Chinese male population]. AB - OBJECTIVE: To investigate the polymorphism of (CAG)n repeats within androgen receptor (AR) gene among normal Chinese male population. METHODS: dsDNA cycle sequencing and[alpha-(32)PdCTP] incorporated asymmol/Letric PCR-denaturing polyacrylamide gel electrophoresis(PAGE) were used to determine the number of (CAG)n repeats in normal men (n=107). RESULTS: The number of polymorphic (CAG)n repeats ranges from 11 to 29; the most frequent repeat is 22(20/107); the less frequent repeats are 23(15/107), 24(11/107), 21(11/107) and 20(8/107). CONCLUSION: The AR gene (CAG)n exhibits polymorphism among normal male population and the present work could serve as a basis for further exploration of its pathological and genetic significance. PMID- 11774216 TI - [Analysis of loss of heterozygosity on 19p in primary gastric cancer]. AB - OBJECTIVE: To investigate the loss of heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci. PMID- 11774217 TI - [Association between renin-angiotensin system gene polymorphism and type 2 diabetics with stroke in China]. AB - OBJECTIVE: The aim of this study was to explore the association between gene polymorphisms of renin-angiotensin system (RAS) and type 2 diabetes mellitus (DM2) complicated with stroke. METHODS: Angiotensin 1-converting enzyme (ACE) genotypes and type 1 angiotensin II receptor(AT1R) genotypes were investigated with PCR and PCR/DdeI enzyme digesting techniques in 152 cases of DM2. RESULTS: No significant differences in genotype frequencies of AT1R gene were found between DM2 complicated with stroke and that without stroke (P> 0.05). The C allele frequency of AT1R gene in DM2 with stroke was higher than that in DM2 without stroke (6.8% vs 1.9% P< 0.05; OR=3.693, 95% CI: 0.977-13.704). The ACE DD genotype and D allele frequencies were higher in DM2 with stroke than in DM2 without stroke(51.4% vs 33.3%, P<0.05; 69.6% vs 54.5%, P<0.05). There was interaction between AT1R gene A1166C polymorphism and ACE gene I/D polymorphism in the development of stroke in DM2 patients (P<0.05; OR=4.00, 95% CI: 0.733 21.838). Logistic regression analysis showed that ACE DD genotype, systolic blood pressure and serum uric acid level were risk factors of DM2 complicated with stroke. CONCLUSION: It is suggested that ACE gene I/D polymorphism is a susceptible gene for stroke in DM2 patients in China. AT1R gene A1166C polymorphism contributes to the development of stroke in DM2 patients, but it is not an independent risk factor. There is synergistic effect of AT1R A1166C and ACE I/D gene polymorphisms on the occurrence and development of stroke in type 2 diabetics in China. PMID- 11774218 TI - [Microsatellite polymorphisms at the TNF locus in Hubei Han population]. AB - OBJECTIVE: To investigate the distribution of tumor necrosis factor(TNF) microsatellite polymorphisms in Chinese. METHODS: DNA was extracted from 164 unrelated healthy individuals' EDTA-blood. TNF microsatellite alleles were typed using PCR technique followed by high voltage denaturing PAGE with silver staining at the same time the PCR products were cloned and sequenced. RESULTS: Thirteen alleles and forty kinds of genotypes were detected at the TNFa locus; two alleles and three kinds of genotypes at the TNFa locus. The polymorphism information contents (PIC) were 0.80 and 0.28 respectively no deviation from Hardy-Weinberg equilibrium was observed. Statistical analysis showed that the distribution of TNFa allele frequencies in Chinese Han population was significantly different from that in European Caucasian or in Japanese P<0.01. The result of sequencing revealed that the copy number of dinucleiotide repeats within the same TNF allele was not consistent with that in the reports from western countries. CONCLUSION: There exists ethnic difference in the distribution of TNFa allele. Further investigations will be necessary to define more accurately and clearly the TNFa alleles. PMID- 11774219 TI - [Detection of BCL2 translocation in an interphase neucleus using fluorescence in situ hybridization strategy]. AB - OBJECTIVE: To establish a specific method to diagnose non-Hodgkin's lymphoma in clinic. METHODS: Fluorescence in situ hybridization (FISH) strategy capable of detecting t(14;18)(q32;q21) chromosome translocation in an interphase nucleus was developed using a YAC clone containing the BCL2 gene and a phage clone containing IgHC(mu) region as probes. In the SU-DHL-6 cells, the translocated BCL2 allele (red) is overlapped by one of the green signals from IgH phage probe, while in normal lymphocytes the least distance of the hybridization signals from two different probes was either equal or larger than one-tenth of the diameter of a nucleus. RESULTS: Based on the relative position of the signals from BCL2 and IgH probes the BCL2 translocation can be clearly detected in an interphase nucleus. The metaphase number and quality in samples, which could significantly restrict the reliability of cytogenetic analysis, can be ignored here. CONCLUSION: This method shows a potentiality in clinical diagnosis of non-Hodgkin's lymphoma because of its objectivity, reliability and simplicity. PMID- 11774220 TI - [The transfer and expression of human clotting factor IX in muscle mediated by electroporation]. AB - OBJECTIVE: To probe into the feasibility of increasing hFIX cDNA transfer and expression in muscle. METHODS: The high-frequency electric field was used to promote both Lac-Z-encoding plasmid pCMV beta and hFIX-expressing plasmid G1NaMCIX to transfer and express in muscle. The effects of frequency and length of square pulse, as well as eletroporation time on hFIX expression were investigated. RESULTS: Electric stimulation could increase the transfer and expression of pCMV beta in muscle, the number of X-gal positive myofiber cells in electroporation-treated mice is 2.1 times larger than that of mice not treated by electroporation (P<0.01). The most optimal electric simulation condition for hFIX cDNA transfer and expression was obtained, under this condition, the highest level of hFIX antigen in plasma is (40+/- 5.4) ng/ml and 7 times higher than that of mice without electroporation P < 0.001). CONCLUSION: Electroporation is able to enhance hFIX cDNA transfer and expression in muscle efficiently. PMID- 11774221 TI - [Single nucleotide polymorphisms(SNPs)and SNP databases]. AB - Along the rapid development of human genome sequencing project, the variation data of human DNA sequence has become more and more useful not only for studying the origin, evolution and the mechanisms of maintenance of genetic variability in human populations, but also for detection of genetic association in complex disease such as diabetes, obesity, hypertension, Alzheimer's disease, etc. In recent two years, the databases such as dbSNP, CGAP, HGBASE, JST and Go!Poly etc. to collect and exploit data of genomic polymorphisms mainly single nucleotide polymorphisms (SNPs) have been respectively established in the United States, European countries, Japan and China. This overview summarized the development and applications of those SNP databases and also discussed some issues regarding the potential improvement of accuracy of SNP data collected. China has one fifth population in the world. Therefore, development of the SNP database for Chinese populations is of importance in developing complete SNP databases of human genome and may also stimulate the further development of biomedical research and production in China. PMID- 11774222 TI - [Introduction to Go! Poly, a human genome polymorphism database]. AB - Databases play an important role in the study of genetic polymorphism. To meet the need for more studies of human genome polymorphism by Chinese medical and pharmaceutical community, a gene oriented human genome polymorphism database-Go! Poly was constructed. As a generalized polymorphism database, Go! Poly extracted human gene-linked sequence variations of all common types from various public resources including scientific journals and Web resources such as HGBASE (http://hgbase.cgr.ki.se) and dbSNP (http://www.ncbi.nlm.nih.gov/SNP/). The polymorphism data were then categorized into different gene loci, and the reference sequences given by LocusLink were used as positioning reference. To facilitate the use, a friendly web interface and a text based query strategy were implemented. Users can fetch specific polymorphism data in just three steps: find specific gene locus by simple search, display sequence variation information of a specific gene locus select, and view the final result of a specific variation site. Besides, a web-based submission tool is provided for direct submission, which can make the polymorphism information generated by the Chinese scientific community available from this resource. PMID- 11774223 TI - Editorial: Bruce Merrifield at the "Crossroads of Chemistry and Biology". PMID- 11774224 TI - Solid phase synthesis of complex natural products and libraries thereof. AB - Natural products have served as an important source of medicinal compounds and pharmaceutical leads over the last century. Within the last 10 years, significant interest has developed in applying combinatorial chemistry techniques to the study of natural products and their biological activities. In this review, we examine several representative efforts wherein natural product skeletons have been constructed or immobilized on solid support and subsequently derivatized, giving rise to analog libraries useful in understanding the structure-activity relationships of the parent natural product. Issues such as target selection, library design, linker development, automation, and library characterization are addressed. PMID- 11774225 TI - Methods and strategies of peptide ligation. AB - This review focuses on the concept, methods, and strategies of orthogonal peptide ligation. It updates our previous review in 1999 on the same subject matter in Biopolymers (Peptide Science, 1999, Vol. 51, p. 311). Orthogonal peptide ligation is an amino terminal specific method to couple chemically unprotected peptides or proteins derived from synthetic or biosynthetic sources. Unlike conventional chemical methods, peptide ligation methods do not require coupling reagents or protection schemes, but are achieved through a variable chemoselective capture step and then an invariable intramolecular acyl transfer reaction. It is also a convergent method with the fewest steps. More than a dozen orthogonal ligation methods have been developed based on captures by either imine or thioester chemistries to afford native and unusual amino acids at ligation sites of linear, branched, or cyclic peptides. The ligation strategies for multiple segments including sequential and tandem ligations are also discussed. PMID- 11774226 TI - Proteomics in the post-genome age. AB - The genome sequencing effort has helped spawn the burgeoning field of proteomics. This review article examines state-of-the-art proteomics methods that are helping change the discovery paradigm in a variety of biological disciplines and, in particular, protein biochemistry. The review discusses both classical and novel methods to perform high-throughput qualitative and quantitative "global" as well as targeted proteome analysis of complex biological systems. From a drug discovery standpoint, the synergy between genomics and proteomics will help elucidate disease mechanisms, identify novel drug targets, and identify surrogate biomarkers that could be used to conduct clinical trials. PMID- 11774227 TI - Solid phase synthesis of mixture-based acyclic and heterocyclic small molecule combinatorial libraries from resin-bound polyamides. AB - The development of soluble mixture-based heterocyclic combinatorial libraries derived from amino acids and peptides is described. Starting with a "toolbox" of various chemical transformations, including alkylations, reductions, acylations, and the use of a variety of bifunctional reagents, the "libraries from libraries" concept has been expanded to encompass the development of more than fifty positional scanning combinatorial libraries each composed of tens of thousands of low molecular weight acyclic and heterocyclic compounds. PMID- 11774228 TI - Phage-display evolution of tyrosine kinases with altered nucleotide specificity. AB - The problem of identifying downstream targets of kinase phosphorylation remains a challenge despite technological advances in genomics and proteomics. A recent approach involves the generation of kinase mutants that can uniquely use "orthogonal" ATP analogs to phosphorylate substrates in vivo. Using structure based design, mutants of several protein kinase superfamily members have been found; robust and general methods are needed, however, for altering the nucleotide specificity of the remaining kinases in the genome. Here we demonstrate the application of a new phage display technique for direct functional selection to the identification of a tyrosine kinase mutant with the ability to use N6-benzyl-ATP. Our method produces, in five rounds of selection, a mutant identical to the best orthogonal Src kinase found to date. In addition, we isolate from a larger library of kinase mutants a promiscuous clone capable of using many different ATP analogs. This approach to engineering orthogonal kinases, combined with others, will facilitate the mapping of phosphorylation targets of any kinase in the genome. PMID- 11774229 TI - New reagents, reactions, and peptidomimetics for drug design. AB - It has been a major focus in our laboratories to prepare novel reagents and peptidomimetic structures for drug design. We have designed and prepared novel guanidinylation reagents that can be employed in solution or as solid phase reagents. We and others have utilized the reagent 3-(diethoxyphosphoryloxy)-1,2,3 benzotriazin-4(3H)-one (DEPBT) for amide bond formation to couple sterically hindered structures. These couplings proceed with remarkably strong resistance to racemization. In the area of peptidomimetics, we have incorporated novel building blocks to create biologically active compounds. These building blocks include thioether and alkylamine bridges, beta-methylated, and beta,beta-dimethylated amino acid residues. These mimetic structures have been incorporated into specific target molecules such as opioids to obtain cyclic peptidomimetics with potent and selective biological activity. PMID- 11774230 TI - Peptide interactions with G-protein coupled receptors. AB - Peptide recognition by G-protein coupled receptors (GPCRs) is reviewed with an emphasis on the indirect approach used to determine the receptor-bound conformation of peptide ligands. This approach was developed in response to the lack of detailed structural information available for these receptors. Recent advances in the structural determination of rhodopsin (the GPCR of the visual system) by crystallography have provided a scaffold for homology modeling of the inactive state of a wide variety of GPCRs that interact with peptide messages. Additionally, the ability to mutate GPCRs and assay compounds of similar chemical structure to test a common binding site on the receptor provides a firm experimental basis for structure-activity studies. Recognition motifs, common in other well-studied systems such as proteolytic enzymes and major histocompatibility class receptors (MHC) are reviewed briefly to provide a basis of comparison. Finally, the development of true peptidomimetics is contrasted with nonpeptide ligands, discovered through combinatorial chemistry. In many systems, the evidence suggests that the peptide ligands bind at the interface between the transmembrane segments and the extracellular loops, while nonpeptide antagonists bind within the transmembrane segments. Plausible models of GPCRs and the mechanism by which they activate G-proteins on binding peptides are beginning to emerge. PMID- 11774231 TI - Total chemical synthesis of human activin beta(A)[12-116] and related large-loop polypeptides. AB - We report here the synthesis, purification, and characterization of several large polypeptides related to the human activin beta(A) subunit and their cyclic counterparts. In particular, we describe for the first time the total chemical synthesis of a 105-mer polypeptide, des[1-11] activin beta(A), and related large loop polypeptide, by an optimized solid phase synthetic protocol based on 9 flouroenylmethyoxycarbonyl (Fmoc) chemistry. These studies show that automated chemical synthesis utilizing Fmoc-based solid phase synthetic strategies provides a practical alternative to recombinant DNA technology for the production of activin-related subunits, with the opportunity to rapidly provide different analogues and structural variants for subsequent structure-function and associated biophysical investigations. PMID- 11774232 TI - Antennapedia/HS1 chimeric phosphotyrosyl peptide: conformational properties, binding capability to c-Fgr SH2 domain and cell permeability. AB - With the aim of interfering with the signaling pathways mediated by the SH2 domains of Src-like tyrosine kinases, we synthesized a tyrosyl-phospho decapeptide, corresponding to the sequence 392-401 of HS1 protein, which inhibits the secondary phosphorylation of HS1 protein catalyzed by the Src-like kinases c Fgr or Lyn. This phospho-peptide was modified to enter cells by coupling to the third helix of Antennapedia homeodomain, which is able to translocate across cell membranes. Here we present CD and fluorescence studies on the conformational behavior in membrane-mimicking environments and on lipid interactions of Antennapedia fragment and its chimeric phosphorylated and unphosphorylated derivatives. These studies evidenced that electrostatic rather than amphiphilic interactions determine the peptide adsorption on lipids. Experiments performed with recombinant protein containing the SH2 domain of c-Fgr fused with GST and with isolated erythrocyte membranes demonstrated that the presence of the N terminal Antennapedia fragment only slightly affects the binding of the phospho HS1 peptide to the SH2 domain. In fact, it has been shown that in isolated erythrocyte membranes, both phospho-HS1 peptide and its chimeric derivative greatly affect either the SH2-mediated recruitment of the c-Fgr to the transmembrane protein band 3 and the following phosphorylation of the protein catalyzed by the Src-like kinase c-Fgr. The ability of the chimeric phospho peptide to enter cells has been demonstrated by confocal microscopy analysis. PMID- 11774233 TI - Noncovalent interactions of peptides with porphyrins in aqueous solution: conformational study using vibrational CD spectroscopy. AB - Noncovalent interactions of poly(L-lysine) (PL), oligopeptides L-lysyl-L-alanyl-L alanine and (L-lysyl-L-alanyl-L-alanine)(2) with meso-tetrakis(4 sulfonatophenyl)porphine (TPPS), and poly(L-glutamic acid) (PLGA) with meso tetrakis(1-methyl-4-pyridyl)porphine tetra-p-tosylate (TMPyP) in aqueous solutions have been studied using combination of spectroscopic methods: Vibrational circular dichroism (VCD) spectroscopy in the mid-infrared region provides a direct information on conformational changes of the polypeptides and oligopeptides caused by interactions with porphyrins; ultraviolet-visible absorption, fluorescence, and electronic circular dichroism (ECD) reveal the aggregation characterization of the porphyrin part of the complexes. Interactions of TPPS with tripeptide, hexapeptide, and PL containing about ten amino acid residues in the molecular chain are accompanied with the changes of VCD patterns in the amide I' region. In these cases, the conformation of the oligopeptide part of complexes is obviously influenced by interactions with TPPS and partial changes of random coil structure are observed in VCD. When PL was composed of the hundreds of lysine residues, just a weak intensity decrease was detected and the shape of VCD spectrum typical for the random coil structure was preserved. As follows from the uv-vis absorption and fluorescence spectra, porphyrin molecules are attached to peptides by electrostatic interaction as a monomer or dimer and interaction between porphyrin and peptide depends on the polypeptide chain length. For the PLGA-TMPyP system with PLGA containing from tens to hundreds of glutamic acid residues in the chain, the VCD spectra were unchanged when TMPyP was presented in the aqueous solution of PLGA and random coil conformation of PLGA-TMPyP aggregates was preserved. PMID- 11774234 TI - Enthalpy distribution for the alpha-helix/random coil transition in a model peptide: a study of two-state behavior. AB - We use heat capacity data of Taylor et al. to calculate the enthalpy distribution of a model peptide using the moments/maximum-entropy method. The peptide was designed with small covalent loops at both ends of the molecule to nucleate alpha helix thus giving a system that would be expected to show a helix-coil transition that is very close to being two state. If we subtract a background contribution from the heat capacity data, then the enthalpy distribution we obtain shows two distinct peaks representing helix and coil. The difference in the peak enthalpy values agrees closely with the DeltaH obtained from the two-state analysis. On the other hand, if we use the complete heat capacity without subtracting background we then obtain an enthalpy distribution that has only a single peak at all temperatures. We show that this result can be consistent with the existence of two states, helix and coil, but only if the range of variation of the enthalpy of each species is so large as to make the notion of a species fairly meaningless. PMID- 11774235 TI - Extended form of a retro-inverso peptide stabilized by beta-sheet unidirectional H-bonds: Crystallographic and NMR evidence. AB - The crystallographic investigation of the retro-inverso peptide Bz-S-gAla-R-mAla NHPh reveals an extended backbone conformation where the NH groups of the gem diamino alkyl moiety and the CO groups of the malonyl residue face side by side. This extended conformation, presenting all carbonyls on opposite sides of the NH groups, is stabilized by interstrand H-bonds running in a single direction of the parallel beta-sheets that characterize the crystal packing. These sheets differ from the beta-sheets formed by native amino acids only. (1)H-NMR nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that a conformation similar to that found in the crystal also prevails in dimethylsulfoxide solution. Previous potential energy calculations of gem-diamino alkyl (g) and malonyl (m) Ala residues predicted that extended forms were less stable than the helical ones because of strong electrostatic repulsions between the parallel polar groups. Similar arguments were invoked to give more weight to helical forms of the retro peptide units in the proposal of packing models of some nylons in their crystalline polar regions. The present findings show that both g and m Ala residues can experience the extended conformation in the beta-sheet aggregation. The energy increase occurring in one strand, due to the parallel orientation of consecutive peptide dipoles, is more than compensated by favorable cooperative interactions among head-to-tail aligned peptide dipoles of facing strands, resulting in the formation of two C==O...H==N H-bonds per residue. PMID- 11774236 TI - Downregulation of estrogen-metabolizing 17 beta-hydroxysteroid dehydrogenase type 2 expression correlates inversely with Ki67 proliferation marker in colon-cancer development. AB - The 17HSDs are a group of isozymes that catalyze the interconversion between high activity 17 beta-hydroxysteroids and low-activity 17-ketosteroids. In the present study, we characterized the expression of 17HSD types 1 and 2 in normal and malignant gastrointestinal tissues and cells. Using the colon as a model for cancer of the gastrointestinal tract, expression of the 17HSD enzymes in cancer development was studied and correlated with proliferation and differentiation markers as assessed by Ki67 and mucin staining, respectively. In normal colon and small intestine, 17HSD type 2 mRNA was expressed in the surface epithelial cells and, to a lesser extent, in the cryptal epithelial cells. In colon-cancer specimens, 17HSD type 2 expression was downregulated both in the tissues and in the cell lines and correlated inversely with the proliferation marker. No expression for the 17HSD type 1 enzyme was observed in normal or cancerous gastrointestinal tract tissues. In line with the expression studies, 17HSD activity measurements with colon cells showed that only the oxidative conversion of E2 to E1 was present, and Northern blot analysis showed the signal only for 17HSD type 2. Localization of the ERs alpha and beta, assessed by immunohistochemistry and in situ hybridization, showed the presence of ER beta in the lamina propria of the colon. Our study shows that 17HSD type 2 expression is associated with the functional integrity of the gastrointestinal tract. The decrease in expression of the type 2 enzyme may increase estrogen influence in colon cancer. PMID- 11774237 TI - Epidermal growth factor receptor mutation type III transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype. AB - In the present study we transfected the epidermal growth factor receptor (EGFR) negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3 EGFRvIII cells had a approximately 5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions. PMID- 11774238 TI - Identification and characterization of the murine ortholog (brms1) of breast cancer metastasis suppressor 1 (BRMS1). AB - We have cloned a novel metastasis-suppressor gene (BRMS1) by differential display, comparing metastatic human breast carcinoma cell line MDA-MB-435 to its metastasis-suppressed human chromosome 11 microcell hybrid. Screening of a murine cDNA library led to the identification of a 1.4 kb cDNA with a sequence revealing 85% homology to human BRMS1 within the open reading frame. The predicted protein sequence for the murine ortholog is 95% identical, suggesting that it is strongly conserved across these 2 species. The cloned cDNA was used to screen a murine strain SV129 BAC library to obtain brms1 genomic DNA. Three BAC clones [226(I4), 226(H4) and 239(N7)] were confirmed to encode the entire brms1 gene. Detailed analysis of BAC clone 226(I4) shows that the gene spans 8.5 kb and, like the human gene, is organized into 10 exons and 9 introns. While the exons share a high degree of homology, there are greater differences when comparing intron structures between the human and murine genes. The 5' upstream region shares about 64% homology with its human counterpart, retaining several of the many putative regulatory elements. Like the human genomic BRMS1, the murine ortholog of the iGnT gene is found upstream of brms1 and the murine ortholog of the RIN1 gene is found downstream of brms1. brms1 was then tested for suppression of metastasis of mouse mammary carcinoma cell line 66cl4 in syngeneic BALB/c mice. Transfection with brms1 did not inhibit 66cl4 primary tumor formation but significantly suppressed its metastatic capability. This suggests that the murine ortholog functions similarly to BRMS1. PMID- 11774239 TI - Expression of heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) in human colorectal carcinoma. AB - Gamma-glutamylcysteine synthetase (gamma-GCS) is a heterodimer consisting of heavy (gamma-GCSh) and light (gamma-GCSl) subunits. gamma-GCS catalyzes the rate limiting de novo biosynthesis of glutathione (GSH), an abundant physiological antioxidant that plays important roles for regulating oxidative stress. Expression of gamma-GCSh and gamma-GCSl are sensitive to oxidative stress. To investigate whether expression of gamma-GCS is correlated with tumor progression, we used immunohistochemical approaches to examine 16 human colorectal adenomas and resected 57 carcinomas from untreated patients. In adjacent normal colorectal epithelium, levels of gamma-GCSh expression were low. Strong cytoplasmic staining for gamma-GCSh was detected in 3 (18.8%) adenoma and 48 (84.2%) carcinomas. The frequency of gamma-GCSh expression in carcinoma was significantly higher than in adenoma (p<0.0001). We used RNase protation assay and Western blot to determine levels of gamma-GCSh mRNA and protein from 10 pairs of matched carcinomas with adjacent normal controls. Elevated expression of both gamma-GCSh mRNA and protein were found in 6 cases, suggesting that transcriptional and/or posttranscriptional regulation play an important role in the upregulation of gamma-GCS during colorectal carcinogenesis. We also examined the expression of another redox regulated gene, multidrug resistance protein 1 (MRP1). Strong staining for MRP1 was detected in 1 (6.3%) adenoma and 40 (70.2%) carcinomas. The frequency of MRP1 expression in carcinoma was significantly higher than in adenoma ( p<0.0001). Nuclear p53 expression was detected in 30 (52.6%) of carcinomas. There is a significant correlation between gamma-GCSh and MRP1 expression (p=0.013) but not between gamma-GCSh and p53. Since gamma-GCS is a sensor of oxidative stress, these results are consistent with the notion that oxidative stress is associated with colorectal tumor progression. PMID- 11774240 TI - Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: gene expression profiles in bone marrow target cells. AB - The red bone marrow (BM) is an important indicator organ of hematogenous micrometastatic spread of carcinomas. Characterization of biological properties specific for BM micrometastatic cells, however, is technically challenging due to the limited number of target cells usually available for the purpose. This report provides referrals to qualitative gene expression profiling of BM micrometastatic cells enriched by immunomagnetic selection. First, an experimental strategy was used to study regulatory mechanisms involved when BM micrometastatic cells colonize distant organs. The MA-11 cells, originating from BM micrometastases in a breast cancer patient clinically devoid of overt metastatic disease, were injected into immunodeficient rats. Metastatic MA-11 cells were subsequently immunoselected from the resulting in vivo lesions. The selected cell populations were compared to the injected cells by differential display analysis, and several genes possibly involved in tumor cell invasion and proliferation were confirmed as differentially expressed among the various MA-11 cell populations. A direct approach to qualitative gene expression profiling of BM micrometastatic cells was also explored. Carcinoma cells were immunoselected from BM and axillary lymph nodes obtained from breast cancer patients, and the isolated cell populations were compared by differential display analysis. Two candidate genes, identified as factors involved in cellular growth control, appeared as differentially expressed by the target cells from BM. Our study provides detailed information on how to combine an immunomagnetic selection procedure and differential display analysis to reveal gene expression profiles that may characterize BM micrometastatic cells. PMID- 11774241 TI - Cu/Zn superoxide dismutase plays a role in angiogenesis. AB - Endothelial cells produce oxygen radicals spontaneously and this process is augmented by hypoxia/reoxygenation. Cu/Zn superoxide dismutase (SOD-1) is an important enzyme in cellular oxygen metabolism. To determine whether alterations in SOD-1 activity affect angiogenesis we used transgenic SOD-1 (Tg-SOD) mice with elevated level of SOD-1. Angiogenesis induced subcutaneously by bFGF in Tg-SOD mice was 3-fold higher than in control non-transgenic (ntg) mice. Oral administration of disulfiram (DSF), an inhibitor of SOD-1, inhibited angiogenesis in Tg-SOD mice as well as in CD1 nude mice. Effects of DSF on cultured cells were also tested. Application of DSF to cultured bovine capillary endothelial (BCE) cells caused inhibition of DNA synthesis and induction of apoptosis. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. DSF also reduced the level of glutathione and the production of H(2)O(2) in BCE cells. Moreover, PC12-SOD cells with elevated SOD-1 were less sensitive to DSF treatment then control cells. These data indicate that the effects of DSF are mediated by inhibition of SOD-1 activity. Tumor development is known to largely depend on angiogenesis. We found that oral administration of DSF to mice caused significant inhibition of C6 glioma tumor development and marked reduction (by 10-19-fold) in metastatic growth of Lewis lung carcinoma. The data suggest a role for SOD-1 in angiogenesis, establish DSF as a potential inhibitor of angiogenesis and raise the possibility that attenuating SOD-1 activity may be important in treatment of angiogenesis-dependent pathologies. PMID- 11774242 TI - Cell type- and promoter-dependent modulation of the Wnt signaling pathway by sodium butyrate. AB - The Wnt signaling pathway modulates the transcription of genes linked to proliferation, differentiation and tumor progression. beta-Catenin-Tcf (BCT) dependent Wnt signaling is influenced by the short-chain fatty acid sodium butyrate, which induces growth arrest and/or maturation of colonic carcinoma cells. We have compared the effects of sodium butyrate on BCT-dependent signaling in 2 colon carcinoma cell lines that differ in their physiologic response to butyrate, with SW620 cells responding to butyrate by undergoing terminal differentiation and apoptosis, and HCT-116 cells undergoing reversible growth arrest, but no significant apoptotic cell death. Furthermore, these colon carcinoma cell lines differ in their mechanism of Wnt pathway activation, with adenomatous polyposis coli (APC) mutant SW620 cells having high levels of BCT complexes and APC wild-type HCT-116 cells having mutant beta-catenin, low levels of BCT complexes and correspondingly higher levels of free Tcf. We have demonstrated that in SW620 cells, butyrate downregulates BCT-dependent expression of the Tcf-TK, matrilysin and cyclin D1 promoters, whereas in HCT-116 cells, butyrate upregulates expression of these promoters. Cotransfection with expression vectors that interfere with the Wnt pathway suggests that butyrate enhances BCT complex-DNA binding. Butyrate reduces the expression of Tcf4 in HCT 116 cells, consistent with the induction by butyrate of Tcf-repressible promoters in these cells. These findings indicate that sodium butyrate modulates the Wnt pathway in SW620 and HCT-116 cells in a different manner and that these differences have consequences for promoter activity that may influence the physiologic response to butyrate. PMID- 11774243 TI - Induction of immune tolerance toward tumor-associated-antigens enables growth of human hepatoma in mice. AB - Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) was previously shown to facilitate suppression of experimental human hepatocellular carcinoma (HCC) expressing HBsAg in athymic mice. We have shown that oral tolerance induces antigen-specific immune suppression of HBsAg by feeding hepatitis B virus (HBV) antigens. In the present study we evaluated the effect of oral tolerance induction toward HBV or HCC antigens on the growth of experimental HCC-expressing HBsAg in mice. Tolerance induction was induced in mice by 5 oral feedings of 1 microg HBV antigens or HCC-extracted proteins (50 microg protein) before vaccination with recombinant HBsAg. Splenocytes (2 x 10(6)) from these mice were transferred to sublethally irradiated athymic BALB/c mice previously transplanted subcutaneously with 10(7) human hepatoma Hep3B cells. Adoptive transfer of splenocytes immunized toward HBsAg prevented tumor growth. At 4 weeks after splenocyte transplantation, tumor volume and serum alpha-fetoprotein (AFP) levels in athymic mice transplanted with splenocytes immunized to HBsAg were undetectable as compared with 1,048 +/- 738 mm(3) and 2,500 +/- 1,431 ng/ml in recipients of naive splenocytes (p < 0.0001). Mice receiving splenocytes tolerized toward Hep3B cells, as manifested by reduced serum HBs antibody levels, reduced HBV-specific stimulation index and reduced HBV-specific-IFN gamma spot forming cells, had early tumor growth evident by elevated AFP serum levels, weight loss and mortality, which were suppressed at 6 weeks. Mice transplanted with splenocytes tolerized toward HBV antigens did not have direct evidence of tumor growth. Induction of oral tolerance toward HCC-extracted proteins enabled transient tumor growth in this model. This effect was mediated through downregulation of the anti-HBV immune response. PMID- 11774244 TI - Identification of HLA-B27-restricted cytotoxic T lymphocyte epitope from carcinoembryonic antigen. AB - Characterization of epitopes recognized by cytotoxic T lymphocytes (CTLs) in the sequence of tumor antigens is an important step in the development of tumor therapies. Because carcinoembryonic antigen (CEA) is a protein expressed in a high number of epithelial tumors, it is an interesting target to study. We screened for the presence of HLA-B27-restricted CTL epitopes from CEA by studying the binding to HLA-B27 of 31 synthetic peptides predicted to bind to this molecule. This afforded 16 peptides with moderate or high binding affinity. Immunization of HLA-B27 transgenic mice with the best binder peptides yielded 4 immunogenic peptides: CEA(9-17), CEA(9-18), CEA(138-146) and CEA(360-369). However, splenocytes from mice immunized with a vaccinia virus-expressing CEA recognized only CEA(9-18). These CTLs were of the CD8(+) phenotype, which upon stimulation with peptide specifically produced IFN-gamma. Moreover, they did not cross-react against peptides of region 9-18 from proteins of the CEA family. Our results show that CEA(9-18) may induce specific CTL responses against CEA. PMID- 11774245 TI - Improved detection of melanoma antigen-specific T cells expressing low or high levels of CD8 by HLA-A2 tetramers presenting a Melan-A/Mart-1 peptide analogue. AB - MHC class I tetramers containing peptide epitopes are sensitive tools for detecting antigen-specific CD8(+) T-cell responses. We demonstrate here that binding of HLA-A2 tetramers to CD8(+) T cells specific for the melanoma associated antigen Melan-A/MART-1 can be fine-tuned by altering either the bound peptide epitope or residues in the alpha 3 domain of HLA-A2, which is important for CD8 binding. Antigen-specific T cells expressing high levels of CD8 could be detected using HLA-A2 tetramers containing the peptide AAGIGILTV, an epitope which is naturally processed and presented from Melan-A/MART-1. In contrast, low CD8-expressing, antigen-specific T cells could be detected efficiently only by using a mutated HLA-A2 tetramer with an altered CD8 binding site or, less efficiently, using the wild-type HLA-A2 tetramer loaded with the peptide analogue ELAGIGILTV, which is superior in stimulating antigen-specific T-cell responses. Our results suggest ways to optimize the identification and expansion of antigen specific T cells with different requirements for the costimulatory CD8 molecule in facilitating T-cell receptor binding to peptide variants. PMID- 11774246 TI - Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. AB - In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world-wide estimates of 1-, 2-3- and 4-5-year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2-3 and 4-5 years are applicable to the evaluation of initial treatment, clinical follow-up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4-5 and 2-3 of follow-up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex-specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long-term period however different demographic patterns with long-life expectancy in high-income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix. PMID- 11774247 TI - Epidemiology of reproductive and hormonal factors in thyroid cancer: evidence from a case-control study in the Middle East. AB - Thyroid cancer is the second most common neoplasm among women in Kuwait and several other countries in the Middle East. Most of these countries also have relatively high birth and total fertility rates. To examine potential relationships between reproductive and hormonal factors and thyroid cancer, we conducted a population-based case-control interview study among 238 women diagnosed with thyroid cancer and a similar number of individually matched controls in Kuwait. Among the demographic variables, women with 12+ years of education had a significantly reduced risk of thyroid cancer (OR = 0.4; 95% CI: 0.2-0.8; p-trend <0.05). The average age at diagnosis (+/-SD) of thyroid cancer was 34.7 +/- 11 years. Events such as age at menarche, pregnancy, menopausal status and age at menopause were not associated with thyroid cancer. There was an association with age at last pregnancy and parity. Women who had their last pregnancy at ages > or = 30 years were at a significantly increased risk (OR = 2.1; 95% CI: 1.2-3.8); there was also a significant trend in risk with increasing age at last pregnancy. There was a modest increase in risk among women who had borne > or = 5 children (OR = 1.5; 95% CI: 0.9-2.5). A joint analysis of these factors showed that childbearing during the latter half of reproductive life had a substantial effect on the incidence of thyroid cancer; for any given level of parity, there was about a 2-fold increased risk if the age at last pregnancy was > or = 30 years. A substantial recent-birth effect, in relation to subsequent diagnosis of thyroid cancer, was observed during the second and third year after a birth (OR = 2.0; 95% CI: 1.0-4.1). In contrast, spontaneous abortion seemed to have a protective effect. There was a significant decrease in risk among women who had a miscarriage as outcome of first pregnancy (OR = 0.1; 95% CI: 0.03-0.4) and those who had experienced > or = 3 miscarriages (OR = 0.3; 95% CI: 0.1-0.8; p trend <0.05). Overall, any female hormone use was not associated with thyroid cancer risk. New association is suggested for a history of post-partum thyroiditis (OR = 10.2; 95% CI: 2.3-44.8). These data support the hypothesis that reproductive factors and patterns may influence, or contribute to, the risk of thyroid cancer among women. PMID- 11774248 TI - Sun exposure and interaction with family history in risk of melanoma, Queensland, Australia. AB - Sun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age-specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population-based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first-degree relatives without melanoma as controls. Data on lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important. PMID- 11774249 TI - Cancer risk in persons receiving prescriptions for paracetamol: a Danish cohort study. AB - The use of paracetamol has been associated with increased risks for urinary tract cancers and decreased risk for ovarian cancer, although results have been inconsistent. We conducted a population-based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry. Cancer incidence among 39,946 individuals receiving prescriptions for paracetamol was compared with expected incidence based on the North Jutland population who did not receive paracetamol prescriptions, during a 9-year follow-up period. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. Overall, 2,173 cancers were observed with 1,973 expected, yielding a SIR of 1.10 (95% CI, 1.06-1.15). Significantly elevated SIRs were found for cancers of the esophagus (1.9; 95% CI, 1.3-2.8) and lung (1.6; 95% CI, 1.4-1.7). Nonsignificantly increased SIRs were observed for cancers of the liver (1.5; 95% CI, 0.96-2.2), renal parenchyma (1.3; 95% CI, 0.9-1.7) and renal pelvis/ureter (1.6; 95% CI, 0.96-2.6), whereas the SIR for cancer of the urinary bladder was close to unity (1.1; 95% CI, 0.9-1.4). For ovarian cancer, the SIR was close to expectation (0.9; 95% CI, 0.6-1.2) with no evidence of trends with duration of follow-up or number of prescriptions. A similar risk pattern was observed after exclusion of person-time experience following prescription for aspirin or other nonsteroidal antiinflammatory drugs in the study cohort and reference population. Our results do not support a major role for paracetamol in the development of cancers of the urinary tract, and we found little evidence of a protective effect of paracetamol against ovarian cancer. The elevated risks for cancers of the esophagus, lung and liver are most likely a result of confounding variables, but may warrant further investigation. PMID- 11774250 TI - Changes in lung-cancer mortality trends in Spain. AB - Several changes in smoking patterns over the past decades in Spain can be expected to result in a shift in lung-cancer mortality rates. We examined time trends in lung-cancer mortality from 1973-1997 using a log-linear Poisson age period-cohort model. The standardized lung-cancer mortality rate for men almost doubled, from 31.4 per 100,000 in 1973 to 58.6 in 1997, with an average annual increase of 2.7%. Mortality increased for male generations born until 1952 as a consequence of the increasing cigarette smoking in successive birth cohorts. However, the slight downward trend observed for the 2 youngest generations suggests a more favorable outcome of the lung-cancer epidemic among Spanish males in the coming years, if this trend continues. For women, mortality rates were 5 to 9 times lower than those for men, 6.3 per 100,000 in 1973 and 6.4 in 1997. However, the increasing mortality among younger generations born since 1942 reflects the rise in the prevalence of smoking women during the last decades and can be expected to spread to older age groups as a cohort effect, indicating the early phase of the smoking-related lung-cancer epidemic among Spanish females. The decreasing mortality trend observed in women until the late 1980s could be attributed to a lower exposure to environmental tobacco smoke at home as a result of a significant reduction in the prevalence of smoking men. PMID- 11774251 TI - Effects of cytarabine and various anthracyclins on platelet activation: characterization of in vitro effects and their possible clinical relevance in acute myelogenous leukemia. AB - Previous in vitro studies have demonstrated that normal platelets and platelet released mediators can alter in vitro characteristics of human acute myelogenous leukemia (AML) blasts. To further investigate whether platelets can be expected to adhere to and thereby affect AML blasts through their release of soluble mediators into a common microenvironment, we investigated (i) the effects on platelet activation by cytotoxic drugs commonly used in AML therapy; (ii) the occurrence of circulating activated platelets in acute leukemia patients; and (iii) the in vivo and in vitro adherence of platelets to AML blasts. The anthracyclins daunorubicin and idarubicin increased the expression of activation associated membrane molecules (GPIIb/IIIa, CD62P, CD63) by normal platelets, daunorubicin then having the strongest effect. In contrast, cytarabine, epirubicin, doxorubicin and mitoxantrone had no significant effects. Although AML patients did not show increased levels of activated platelets in the circulation, adhesion of platelets to AML blasts was demonstrated both in vivo and in vitro. These results suggest that platelets and AML blasts may locate to common in vivo microenvironments, and platelet-derived soluble mediators may thereby affect the functional characteristics of the leukemia cells. PMID- 11774252 TI - Pegylated liposomal tumor necrosis factor-alpha results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil) in soft tissue sarcoma-bearing rats. AB - Previously we reported that encapsulation of tumor necrosis factor-alpha (TNF) in pegylated (STEALTH) liposomes (TNF-PEGL) dramatically improved circulation times of the protein and augmented accumulation in tumor tissue. We and others have demonstrated enhanced antitumor activity of doxorubicin or melphalan by free TNF when used in high doses in an isolated limb perfusion setting. In the present study the antitumor activity of TNF-PEGL was studied in combination with liposomal chemotherapy. BN rats with subcutaneous BN175 sarcomas (8-12 mm diameter) received no treatment or pegylated liposomal doxorubicin (Doxil) alone or in combination with various doses of TNF-PEGL (15-200 microg/kg). The evaluated endpoints were tumor response and toxicity of the treatment regimens. Here we demonstrate that TNF-PEGL at a dose of 15 microg/kg markedly augments the antitumor activity of liposomal doxorubicin, without resulting in the increased toxic side effects observed with free TNF at doses resulting in a similar enhancement of the antitumor effects. Even at a TNF dose of 200 microg/kg TNF, repeated administration of TNF-PEGL did not result in severe weight loss or cause diarrhea. Repeated dosing of free TNF at this dose resulted in severe, life threatening weight loss and occurrence of diarrhea in all animals. These results indicate that pegylated liposomal encapsulation may be effective in systemic application of TNF for combined treatment with liposomal chemotherapy of advanced solid tumors. PMID- 11774253 TI - Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination. AB - XK469 (NSC 697887) is a novel antitumor agent with broad activity against a variety of tumors. Previous studies suggest that XK469 is a topoisomerase II beta poison with functional activity similar to that of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). The goal of our study was to investigate its mechanism of action further using a human HCT-116 (H116) colon tumor cell model. Concentration-survival curves with continuous exposure indicated that XK469 had low cytotoxic activity against H116 cells. Cell cycle analysis revealed that XK469 is a phase-specific cell cycle blocker that is associated with increased levels of cyclin B1, cyclin A and p53 but not CDK1 (cdc2) or cyclin E. In contrast, treatment of H116 cells with m-AMSA caused a total degradation of both cyclin A and B1 but enhanced expression of cyclin E and p53. Accumulation of cyclin B1 in XK469-treated cells was correlated with the inhibition of cyclin B1 ubiquitination, a metabolic process mandatory for proteasome-mediated protein turnover. However, no inhibition of cyclin B1 ubiquitination was detected in cells treated with m-AMSA or colchicine, a known mitotic inhibitor. Furthermore, unlike m-AMSA, XK469 did not induce caspase activation or apoptotic cell death in H116 cells. Our results suggest that XK469 is a phase-specific cell cycle inhibitor with a unique mechanism of action that is correlated with the inhibition of cyclin B1 ubiquitination and its accumulation at early M phase. PMID- 11774254 TI - Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues. AB - We studied the relationship between response of breast cancer to docetaxel (DOC) or cylophosphamide + epirubucin (CE) treatment and CYP3A4 mRNA expression in breast tumors. CYP3A4 inactivates DOC but not E, which is a predominant effector in CE treatment. Twenty patients with locally advanced breast tumors and 18 patients with locally recurrent tumors underwent tumor biopsy before chemotherapy, and CYP3A4 mRNA expression levels in tumor tissues were assayed by real-time quantitative polymerase chain reaction. Twenty-three patients were treated with DOC (60 mg/m(2) q3w) and 15 patients were treated with CE (C 600 mg/m(2) and E 60 mg/m(2) q3w). Patients with low CYP3A4 mRNA levels (n = 14) exhibited a significantly (p < 0.01) higher response rate (71%) to DOC treatment than those (n = 9) with high CYP3A4 mRNA levels (response rate, 11%). Positive predictive value, negative predictive value and diagnostic accuracy of CYP3A4 mRNA levels in the prediction of response to DOC were 71, 89, and 78%, respectively. However, no significant association was observed between CYP3A4 mRNA expression and response to CE treatment. These results suggest that intratumoral CYP3A4 mRNA levels might be useful as a predictor of response to DOC treatment, but not to CE treatment, in breast cancer patients. The increased inactivation of DOC by CYP3A4 in tumor tissues may play some role in the acquisition of resistance to DOC. PMID- 11774255 TI - Inhibition of spontaneous metastases formation by amifostine. AB - Amifostine was investigated for its ability to inhibit spontaneous metastases formation using the well-characterized murine sarcoma, Sa-NH. Amifostine was administered intraperitoneally at a dose of 50 mg/kg every other day for 6 days to C3Hf/Kam mice until tumors reached an average size of 8-8.5 mm in diameter. Amifostine was again administered immediately after surgical removal of the tumor bearing limbs by amputation, and then once more 2 days later. Twenty-one days later, animals were evaluated for the presence of spontaneously developed pulmonary metastases. Nontumor-bearing control animals were sham treated using the same dosing and surgery schedules. Treatment with amifostine appeared to slightly delay tumor growth, that is, 13 vs. 12 days for tumors to reach an average diameter of 8 mm. Amifostine reduced both the incidence of pulmonary metastases formed in experimental animals from 77% to 57% (p < 0.05), and their average number per animal from 12.8 +/- 5.4 (SEM) to 2.9 +/- 1.1 (SEM). The effect of amifostine exposure on serum levels of the angiogenesis inhibitor angiostatin was also determined using Western blot analysis. Consistent with the antimetastatic effect, exposure of animals to 50 mg/kg of amifostine resulted in a 4-fold enhanced serum level of angiostatin above control levels. This phenomenon occurred in tumor-bearing and nontumor-bearing animals. The effects of amifostine on matrix metalloproteinase (MMP) enzymatic activity was also determined using gelatin zymography. Conditioned growth medium collected from Sa NH cells grown to confluency was exposed to various concentrations of SH, i.e., 2 [(aminopropyl)amino]ethane-thiol (WR-1065), the active thiol form of amifostine, for either 30 min or 18 hr. WR-1065, as a function of increasing dose and time, inhibited the enzymatic activities of MMP-2 and MMP-9. At a concentration and time of exposure likely to be achieved in vivo, that is, 40 microM and 30 min, MMP-2 and MMP-9 activities were reduced to between 30% and 40% of control values. Consistent with these affects, WR-1065 was also found to be effective in inhibiting the ability of Sa-NH cells to migrate through Matrigel membranes. After an 18-hr exposure under in vitro conditions, WR-1065 at concentrations of 4, 40 and 400 microM, and 4 mM, inhibited Sa-NH migration to 11%, 44%, 81% and 97% of control values, respectively. The abilities of amifostine and its active thiol WR-1065 to stimulate angiostatin production in mice, and to inhibit the MMP enzymatic activities and invasion ability of Sa-NH cells under in vitro conditions, are consistent with the observed antimetastatic effects exhibited against Sa-NH tumors growing in vivo. PMID- 11774256 TI - Transforming growth factor-beta and Ras regulate the VEGF/VEGF-receptor system during tumor angiogenesis. AB - The formation of new microvasculature by capillary sprouting, or angiogenesis, is a prerequisite for solid tumor growth. The genetic alterations required to activate the angiogenic program in tumor angiogenesis are still only vaguely known, but dominantly acting oncoproteins may have a much greater impact than previously realized. Here we have studied the consequences of oncogenic transformation on tumor angiogenesis in a mouse mammary carcinoma model. We provide evidence that the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptor-2 (Flk-1), a signaling system centrally involved in tumor angiogenesis, occurs efficiently in tumors formed by Ras-transformed mammary epithelial cells and that both TGF-beta1 and hypoxia are potent inducers of VEGF expression in these cells. VEGF induction in the tumor periphery is mainly triggered by TGF-beta1, whereas VEGF expression in perinecrotic areas is regulated by both hypoxia and TGF-beta1. As the Ras-transformed tumor cells convert into migrating, fibroblastoid cells that start to produce TGF-beta during tumor progression, the TGF-beta effect on VEGF expression becomes propagated throughout the tumor tissue. Thus, in progressed tumors, areas of TGF-beta1 activation and hypoxia may overlap and hence cooperate to induce VEGF expression and angiogenesis. Nevertheless, the overexpression of VEGF in non-Ras-transformed mouse mammary epithelial cells was not sufficient to promote vascularization in vivo. Based on these findings, we conclude that amongst the multiple mutations that render a normal cell tumorigenic, oncogenic Ras is a major player that in conjunction with the tumor's micro-environment sets the stage for tumor cell invasion and angiogenesis. PMID- 11774257 TI - A very early induction of major vault protein accompanied by increased drug resistance in U-937 cells. AB - U-937 human leukemia cells were selected for resistance to doxorubicin in the presence or absence of a specific drug modulator that inhibits the activity of P glycoprotein (Pgp), encoded by the multidrug-resistance gene (MDR1). Parental cells expressed low basal levels of the multidrug-resistance-associated gene (MRP1) and major vault protein (MVP) mRNAs and no MDR1 mRNA. Two doxorubicin resistant cell lines were selected. Both drug-resistant cell lines upregulated the MVP mRNA level 1.5-fold within 1 cell passage. The MVP mRNA level continued to increase over time as the doxorubicin selection pressure was increased. MVP protein levels generally paralleled the mRNA levels. The 2 high molecular weight vault protein mRNAs were always expressed at constitutive levels. Fully formed vault particles consisting of the MVP, the 2 high molecular weight proteins and the vault RNA assembled and accumulated to increased levels in drug-selected cells. MVP induction is therefore the rate-limiting step for vault particle formation in U-937 cells. By passage 25 and thereafter, the selected cells were resistant to doxorubicin, etoposide, mitoxantrone and 5-fluorouracil by a pathway that was independent of MDR1, MRP1, MRP2 and breast cancer resistance protein. In summary, U-937 doxorubicin-selected cells are programmed to rapidly upregulate MVP mRNA levels, to accumulate vault particles and to become multidrug resistant. PMID- 11774258 TI - Involvement of matrix metalloproteinase type-3 in hepatocyte growth factor induced invasion of human hepatocellular carcinoma cells. AB - Intra-hepatic invasion is a key feature of hepatocellular carcinoma (HCC) progression. We have shown that human liver myofibroblasts induce invasion of HCC cells through Matrigel, via the secretion of hepatocyte growth factor (HGF). In our study, we investigated the role of matrix metalloproteinases (MMP) in HGF induced HCC cells invasion. Marimastat, a synthetic MMP inhibitor, dose dependently decreased HGF-induced invasion of HepG2 cells with a maximum of 82.7 +/- 13.3% at 20 microM. TIMP-2, a natural inhibitor, decreased invasion up to 51.2 +/- 11.2% at 200 ng/ml. To determine the target for these inhibitors, we examined MMP expression using RT-PCR. MMPs 1, 7-9 and 10 were not expressed in HepG2 cells either in the absence or in the presence of HGF. MMP-2 and MMP-13 transcripts were detected in unstimulated cells but their expression was unchanged after exposition to HGF. MMP-3 transcripts were undetectable in unstimulated HepG2 cells. They became clearly expressed in HGF-stimulated cells, however, and this was confirmed by Northern blot. By Western blot, HGF dose dependently stimulated the secretion of pro-MMP-3 in the culture medium. The role of MMP-3 in HGF-induced invasion was directly confirmed by using an antibody to MMP-3, that blocked invasion. Finally, RT-PCR demonstrated MMP-3 expression in 10/16 human HCCs tested, but not in normal liver. In conclusion, our data demonstrate that MMPs, most likely MMP-3, mediate HGF-induced invasion of HCC cells. The in vivo expression of MMP-3 in HCC suggests a role for this protease in HCC progression. PMID- 11774259 TI - VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors. AB - Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide with potent mitogenic effects on endothelial cells. VEGF expression has also been reported in ovarian epithelial tumors (OETs), which may be associated with gonadotropin stimulatioin. We recently reported that most OETs, including OET cell lines, express gonadotropin receptors. Here we studied VEGF mRNA expression in 141 OET and 35 benign ovarian samples using reverse transcriptase polymerase chain reaction and in situ hybridization (ISH). We also studied VEGF production by OET cell lines under stimulation of gonadotropins. AO (serous carcinoma), low malignant potential (LMP; SV40-transformed borderline tumor) and ML-5 (SV40-transformed cystadenoma) cells were examined for VEGF protein production under the regulation of gonadotropins in vitro. The biologic function of VEGF was confirmed by using bovine endothelial growth assay. Whereas VEGF was not detected in benign ovarian surface epithelium or in ovarian epithelial inclusions, it was detected in both epithelial and stromal compartments of OETs. For VEGF epithelial expression, only 5% of ovarian cystadenomas and 30% of borderline tumors were positive for VEGF detection by ISH, whereas VEGF mRNA signal was detected in 80% of ovarian carcinoma cases. This increment of VEGF expression in ovarian carcinomas was statistically significant compared with benign and borderline tumors. Within ovarian carcinomas, the percentage of VEGF-positive cells was significantly associated with the grade of cancer but not with cancer cell types or cancer stages. Both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulated the expression of VEFG(165) in AO cells in a dose-dependent manner. Maximal induction was obtained for FSH at dose of 40 mIU/ml and for LH at 50 mIU/ml after 48 hr of culture. Compared with the nonstimulated cells, VEGF level was significantly elevated in both LMP and AO cells after stimulation of gonadotropins. Furthermore, the induction of VEGF expression was significantly stronger in carcinoma cells than in borderline OET cells. These observations suggest that VEGF may play a role in the development of ovarian cancer and that the elevated gonadotropins, as found in menopause and in most ovarian cancer patients after surgery, could accelerate tumor growth and tumor recurrence by inducing VEGF expression in OETs. PMID- 11774260 TI - Apoptosis induced by low-dose paclitaxel is associated with p53 upregulation in nasopharyngeal carcinoma cells. AB - Paclitaxel exerts its cytotoxic effect by kinetic suppression of microtubules that block cells in the G2/M phase of the cell cycle and trigger apoptosis. To investigate apoptosis induced by paclitaxel in nasopharyngeal carcinoma (NPC), and its possible molecular mechanism of action, the human NPC cell lines HNE-1 (bearing wild-type p53) and CNE-2 (bearing mutant p53) were treated with different concentrations of paclitaxel. Apoptosis was determined by staining with propidium iodide and also by DNA fragmentation. Protein expression levels of p53, bcl-2 and bcl-xl were examined by Western blotting. Activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) were also studied in paclitaxel induced apoptosis. We showed that paclitaxel inhibited growth and induced apoptosis in both cell lines but that the p53 mutant line (CNE-2) was less sensitive to treatment with low-dose paclitaxel. Caspase-3 activity and cleavage of death substrate PARP were significantly increased in a dose-dependent manner, both in parallel with the induction of apoptosis and growth inhibition of NPC cells. We observed a striking increase of p53 protein levels in NPC cells exposed to 1 and 10 nM paclitaxel but a marked inhibition at 100 nM paclitaxel treatment. An inhibitor of caspase, zVAD.fmk, blocked the apoptotic morphologic changes and DNA fragmentation but did not change the rate of cell death or the protein levels of p53, bcl-2 and bcl-xl. In summary, low-dose paclitaxel inhibited cell growth in NPC cells and induced apoptosis possibly by upregulation of p53. In contrast, cell growth and apoptosis induced by a high dose of the drug occurred in a p53 independent manner, which may directly initiate downstream events of apoptosis. PMID- 11774261 TI - Growth inhibition of BEL-7404 human hepatoma cells by expression of mutant telomerase reverse transcriptase. AB - Human hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia and Africa. Human telomerase reverse transcriptase (hTERT) is expressed in HCC but absent in normal human liver cells, which is consistent with the expression pattern of telomerase. In the present study, expression of a dominant negative form of hTERT (DN-hTERT) resulted in inhibition of telomerase activity and decreased mean telomeric length of BEL-7404 human hepatoma cells, whereas expression of wild-type hTERT (WT-hTERT) and control vector had no such effects. Cell growth was inhibited by this mutant (DN-hTERT), which was consistent with the changes in telomerase level. Flattened large cells were found in late generations with the DN-hTERT treatment. When mean telomeric length of DN-hTERT transfected cells reached a critical length (about 1.7 kb), apoptosis was induced. Tumorigenicity of DN-hTERT-expressing cells was eliminated in vivo. These data indicated that hTERT was essential for the growth of hepatoma cells. hTERT can also be used as an important target for anti-HCC drug screening. PMID- 11774262 TI - Reduced sialidase expression in highly metastatic variants of mouse colon adenocarcinoma 26 and retardation of their metastatic ability by sialidase overexpression. AB - Sialidase expression levels are inversely correlated with the metastatic potential of mouse colon adenocarcinoma 26 sublines, as assessed by activity assays and RT-PCR, irrespective of total and cell surface sialic acid contents. Compared with low metastatic NL4 and NL44 cell lines, the highly metastatic NL17 and NL22 cells exhibit low expression of sialidases, accompanied with higher levels of sialylLe(x) and GM3. To investigate whether these properties of NL17 cells can be altered by sialidase overexpression, we transfected a cytosolic sialidase gene into NL17 cells. The result was markedly inhibited lung metastasis, invasion and cell motility with a concomitant decrease in sialylLe(x) and GM3 levels, in line with the case of spontaneously low metastatic sublines having relatively high endogenous sialidase levels, implying that sialidase level is a determining factor affecting metastatic ability. Treatment of the cells with antibodies against sialylLe(x) and GM3 affected cell adhesion and/or cell motility, providing evidence that desialylation of these molecules, as targets of sialidase, is involved in the suppression of metastasis. PMID- 11774263 TI - Altered adhesion properties and alphav integrin expression in a cisplatin resistant human ovarian carcinoma cell line. AB - In order to elucidate the mechanisms underlying the development of chemoresistance in ovarian cancer, we have previously established the IGROV1-R10 cisplatin-resistant cell line by mimicking a clinical protocol of drug administration on IGROV1 human ovarian carcinoma cells. Both IGROV1 and IGROV1 R10 cells were able to grow as a monolayer and to release cell clusters into the medium. However, IGROV1-R10 cells exhibited an enhanced capacity to detach from the monolayer as compared to the parental cells. When substrate adhesion was prevented, IGROV1-R10 cells were able to survive and to proliferate as cell clusters, even at a low cell density, whereas IGROV1 cells massively died. To explore the underlying mechanisms, we have been interested in alphav integrins, which have been implicated in some aspects of ovarian cancer biology. Both IGROV1 and IGROV1-R10 adherent cells expressed alphavbeta3 integrin. During cell growth, alphavbeta5 integrin accumulated at the surface of a majority of IGROV1-R10 cells from the monolayer, whereas only a faint expression of this integrin was observed in a minority of IGROV1 cells. The growth of IGROV1-R10 cells, but not of IGROV1 cells, was partly inhibited by a specific alphavbeta5-blocking antibody suggesting that alphavbeta5 integrin contributed to IGROV1-R10 cell proliferation. PMID- 11774264 TI - Characterization of XAGE-1b, a short major transcript of cancer/testis-associated gene XAGE-1, induced in melanoma metastasis. AB - Suppression subtractive hybridization, comparing mRNA expression profiles of common nevocellular nevi and melanoma metastases, was used to identify potential markers of melanoma progression. From the metastases we isolated XAGE-1b, a 470 bp transcript of the XAGE-1 gene. In general, expression of XAGE-1b was much more prominent than expression of the longer XAGE-1 transcript, isolated from Ewing's sarcoma. The XAGE-1b open-reading frame codes for a putative protein of 81 amino acids, harboring a functional bipartite nuclear localization signal and a C terminal acidic transcription-activation-like domain. On the nucleotide level, XAGE-1b has a 50% homology with members of the GAGE family. However, homology between the corresponding proteins is weak. Expression of XAGE-1b in normal tissues was mainly restricted to testis, while placenta and brain were sporadically positive. In human tumor cell lines as well as in human tumor lesions, expression was most frequently found in melanocytic tumors and Ewing's sarcoma. In the different stages of melanocytic tumor progression, expression was exclusively seen in melanoma metastases (38%; n = 61), while all tested common and atypical nevi (n = 10) as well as primary melanomas (n = 8) were negative. Upregulation of expression after treatment with demethylating agent 5-aza-2' deoxycytidine was detected in 1 of 4 human melanoma cell lines tested. The XAGE-1 gene consists of 4 exons and is located on chromosome Xp11.21-Xp11.22. After transfection into COS cells, the corresponding protein can direct the coupled fluorescent protein to the nucleus, showing a distinct speckled staining aspect. Our data imply the nuclear cancer/testis-associated XAGE-1b to be a marker for late melanocytic tumor progression. PMID- 11774265 TI - Proficient mismatch repair protein expression in Hodgkin and Reed Sternberg cells. AB - Hodgkin and Reed-Sternberg (H/RS) cells are characterized by chromosomal instability. Nevertheless, neither specific nor consistent chromosomal alterations could be characterized in H/RS cells. Microsatellite instability (MSI) is another form of genomic instability but its role in the pathogenesis of classical Hodgkin's disease (cHD) has not been investigated so far. We analyzed MSI and mismatch repair (MMR) protein expression in H/RS cells of cHD in order to assess genomic instability in these cells. Using a sensitive single cell approach, MSI-low was detected in a portion of single cells of the H/RS cell line L1236. Mutations of genes encoding for hMSH2 and hMLH1 were excluded by RT-PCR in L1236 cells. An analysis of pooled single H/RS cells of seven primary cases of cHD showed loss of heterozygosity for some allelic markers but absence of MSI in all 7 cases. Owing to a tight correlation between MSI-high, inactivating mutations of MMR genes and MMR protein expression in colon cancer, MMR protein expression commonly is used as a marker for MSI. In order to screen additional primary cases of cHD for MSI, we performed immunohistochemistry for hMSH2 and hMLH1 in 6 of the 7 cases analyzed by single cell PCR and 20 additional cases of cHD. H/RS cells from 25 out of 26 cases showed a nuclear staining pattern for hMSH2 and hMLH1 similar to germinal center B cells of non-malignant lymph nodes. These results indicate a proficient MMR system in most H/RS cells. It is concluded that a defect MMR system is unlikely to contribute to the malignant phenotype and genomic instability of H/RS cells in cHD. PMID- 11774266 TI - Increased expression of T-fimbrin gene after DNA damage in CHO cells and inactivation of T-fimbrin by CpG methylation in human colorectal cancer cells. AB - When DNA damage is induced by unprogrammed extrinsic events, activating-cell cycle checkpoints delay cell-cycle progression in the G1 or G2 phases and allow repair of a damaged template. In this study, we evaluated changes in gene expression upon radiation-induced G2 cell-cycle arrest using Chinese hamster ovary (CHO) cells. T-fimbrin, an actin-binding protein, was overexpressed in CHO cells in which G2 arrest had been induced by X-radiation. Northern blot analysis revealed that T-fimbrin gene expression was induced not only by X-radiation but also by a topoisomerase II inhibitor, etoposide. Transfection of CHO cells with a vector encoding T-fimbrin antisense RNA demonstrated that reduced T-fimbrin expression induced alterations in cell-cycle control; radiation-induced G2 arrest was short and decreased in cells transfected with antisense T-fimbrin. Additionally, T-fimbrin gene expression was suppressed in a human colorectal cancer cell line, SW948, because of promoter-specific DNA methylation. These results suggest that downregulation of T-fimbrin may be involved in cancer development through G2/M cell-cycle control in mammalian cells. PMID- 11774267 TI - Identification and characterization of 9D7, a novel human protein overexpressed in renal cell carcinoma. AB - With the objective of discovering novel tumor-associated antigens of the cancer/testis type, we compared the transcriptional profiles of renal cell carcinoma (RCC) and non-tumorous kidney and further screened for genes expressed in RCC and testis, but not other normal tissues. In a first step, a representational difference analysis library consisting of approximately 1,900 RCC cDNA clones was generated. Clones were then spotted onto filters and hybridized with cDNA probes derived from a testis-specific cDNA library, a pool of RCCs and a pool of 10 healthy normal tissues, respectively. Based on strong hybridization signals with both RCC and testis, but not normal tissue probes, 185 clones were sequenced and annotated. After EST-database comparison, 35 clones were selected for experimental analysis, including conventional and quantitative RT-PCR as well as Northern blotting. Clone 9D7 showed strong mRNA expression in RCC as well as in several other major tumor types. In normal tissues there was little or no mRNA expression with the exception of heart. 9D7 was cloned to full size and found to represent a novel human gene containing 5 exons residing on chromosome 14. Alternative splicing within exon 1 generates 2 open-reading-frames consisting of 717 or 435 bp corresponding to predicted proteins of 239 or 145 amino acids. 9D7 shows high homology (227/239 amino acids or 95% identity) to a growth factor-inducible gene of Rattus norvegicus involved in apoptosis. In situ hybridization as well as immunohistochemical analysis using 9D7-specific antisera confirmed overexpression of 9D7 in RCCs as compared to normal kidney tissue. PMID- 11774268 TI - Risk factors for Barrett's esophagus: a case-control study. AB - Barrett's esophagus (BE) is an acquired disorder due to chronic gastroesophageal reflux. Environmental factors seem to play an important role in the pathogenesis of BE, especially in Western society. A multicenter case-control study was carried out between February 1995 and April 1999 in 8 Italian Departments of Gastroenterology gathered in a study group (GOSPE), in order to analyze the influence of some individual characteristics and life-style habits on the occurrence of BE. Three groups of patients were studied: 149 patients with BE, 143 patients with esophagitis (E) and 308 hospital controls (C) with acute, non neoplastic, non-gastroenterological conditions. The diagnosis of BE was based on endoscopy and histology. E was defined by the Savary classification (grade I III). Data collection was performed by using a questionnaire that focused on smoking, coffee and alcohol consumption, medical history, drugs history, gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation) and socio-economic status. Multivariate analysis showed that the frequency of weekly GERD symptoms was significantly associated with both BE and E (p<0.0001), such as the presence of hiatal hernia (p< or =0.001). Ulcer was significantly associated with BE (p=0.001). Among patients with E, the risk was directly related to spirits consumption (p=0.03). Patients with GERD symptoms that lasted more than 13 years were more likely to have BE than E (p=0.01). In conclusion, results from our study point out that long-standing GERD symptoms, hiatal hernia and possibly alcohol consumption are risk factors in the development of the BE and E. PMID- 11774269 TI - Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The genetic factors underlying the susceptibility to this disease remain elusive. The enzymes CYP2E1, MPO and NQO1 are involved in the biotransformation of a variety of xenobiotics present in organic solvents, tobacco smoke, drugs, plastic derivatives and pesticides. They also control the level of the oxidative stress by catalyzing the formation of free radicals or by protecting cells from their deleterious effect. DNA variants in the corresponding genes have been associated with an increased susceptibility to different adult cancers, including hematologic malignancies. To investigate whether they represent risk-modifying factors in childhood ALL, we conducted a case-control study involving 174 patients and 337 controls, both of French-Canadian origin. We found that carriers of the CYP2E1*5 variant were at 2.8-fold higher risk of ALL (95%CI, 1.2-6.4) and that NQO1 alleles *2 and *3 contributed to the risk of ALL as well (OR = 1.7, 95%CI, 1.2-2.4). No such association was found with MPO alone. However, when the wild-type MPO allele was considered together with the CYP2E1 and NQO1 risk elevating genotypes, the risk of ALL was increased further (OR = 5.4, 95%CI, 1.2 23.4) suggesting a combined effect. We also found a gene-gene interaction between the GSTM1 null genotype and NQO1 mutant alleles. It is therefore plausible that exposure to xenobiotics metabolized by these enzymes play a role in the etiology of childhood ALL. PMID- 11774270 TI - Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial. AB - Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65 69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48 3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008. PMID- 11774271 TI - A comparative study of normal inspection, autofluorescence and 5-ALA-induced PPIX fluorescence for oral cancer diagnosis. AB - Fluorescence diagnosis aims to improve the management of oral cancer via early detection of the malignant lesions and better delimitation of the tumor margins. This paper presents a comparative study of normal inspection, combined fluorescence diagnosis (CFD) and its 2 main components, autofluorescence and 5 aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence. Biopsy controlled fluorescence imaging and spectral analysis were performed on a total of 85 patients with suspected or histologically proven oral carcinoma both before and after topical administration of 5-ALA (200 mg 5-ALA dissolved in 50 ml of H(2)0). Fluorescence excitation was accomplished using filtered light of a xenon short arc lamp (lambda = 375-440 nm). As for CFD, a "streetlight" contrast (red to green) was readily found between malignant and healthy tissue on the acquired images. In terms of tumor localization and delimitation properties, CFD was clearly favorable over either normal inspection or its 2 components in fluorescence imaging. The performance of CFD was found to be impeded by tumor keratinization but to be independent of either tumor staging, grading or localization. In spectral analysis, cancerous tissue showed significantly higher PPIX fluorescence intensities and lower autofluorescence intensities than normal mucosa. There is a great potential for CFD in early detection of oral neoplasms and exact delimitation of the tumors' superficial margins and an advantage over white light inspection and each of its 2 main components. The method is noninvasive, safe and easily reproducible. PMID- 11774272 TI - Biodistribution of hypericin in orthotopic transitional cell carcinoma bladder tumors: implication for whole bladder wall photodynamic therapy. AB - In a recent clinical study, we reported a selective uptake of hypericin in superficial bladder tumors. The results suggested that hypericin, a potent photosensitizer, could be used not only for diagnosis but also for photodynamic therapy (PDT) of superficial bladder tumors. In the present study, we investigated the biodistribution of hypericin in an orthotopic rat bladder tumor model by assessing the extent of hypericin penetration and the kinetics of accumulation into rat bladder tumors and normal bladder wall. Hypericin (8 or 30 microM) was instilled into the bladder via the catheter for 1, 2 or 4 hr. The fluorescence of hypericin in the bladder tumors and normal bladder was documented using fluorescence microscopy. In situ quantification of hypericin fluorescence in the tumor or normal bladder was performed using the laser-induced fluorescence technique. There was much more hypericin fluorescence in the tumor than in the normal bladder, with the tumor-to-normal-bladder ratio mounting to 12:1 after 4 hr of hypericin (30 microM) instillation. Moreover, hypericin was retained in the tumor for at least 1 hr before it was gradually lost from the tissue. Microscopically, the fluorescence of hypericin was restricted to the urothelial tumor and normal urothelium without fluorescence in the submucosa and the muscle layers. Subsequently no hypericin was detected in plasma, indicating that under these conditions systemic side effects should not be expected. Because the conditions used in this study were similar to those used in our previous clinical study, it is therefore likely that whole bladder wall PDT in the clinic under these conditions will produce selective urothelial tumor destruction without causing damage to the underlying muscle layers. PMID- 11774273 TI - Proteomic alterations of the variants of human aldehyde dehydrogenase isozymes correlate with hepatocellular carcinoma. AB - To develop novel markers for hepatocellular carcinomas (HCC), 10 cases were analyzed by 2-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry. Results were compared to those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE revealed that 3 variants of class 3 aldehyde dehydrogenase (ALDH 3) newly appeared while 2 variants of ALDH-2 diminished to undetectable levels in HCC. However, 4 ALDH-1 variants with different pIs remained unaffected. This pattern of concomitant appearance and disappearance of ALDH-3 and ALDH-2 variants was consistently observed in all HCC tissues. Our results suggest that alterations of ALDH isozyme variants may be closely correlated to HCC and that proteomic analysis of these proteins might be a novel approach to identify the molecular events in detail during hepatocarcinogenesis. PMID- 11774275 TI - Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma. PMID- 11774276 TI - Aberrant methylation and histone deacetylation of cyclooxygenase 2 in gastric cancer. AB - Cyclooxygenase 2 plays a critical role in the development of gastrointestinal cancers in both human and animal models. About 80% of the gastric cancer showed a high level of expression of cyclooxygenase 2, but a subset of cases do not express without unknown reason. Aberrant methylation of CpG island of COX-2 was examined by using a series of gastric cancer cell lines and primary gastric cancers. Two out of 8 cell lines (25%) and 11 out of 93 (12%) primary cancers showed aberrant methylation of the 5' region of COX-2. Methylation of COX-2 was closely associated with loss of expression and treatment of methylation inhibitor, 5-deoxy-2'-azacytidine restored the expression of COX-2. A combined treatment of 5-deoxy-2'-azacytidine and a histone deacetylese inhibitor, trichostatin A, restored re-expression of the gene synergistically and chromatin immunoprecipitation analysis revealed that histone of methylated COX-2 promoter is deacetylated, indicating the role of cytosine methylation and histone deacetylation in the silencing of the gene. These results indicate that a subset of gastric cancer with COX-2 methylation evolves through the pathway that is independent of COX-2 expression and that COX-2 inhibitor may not be useful to induce apoptosis in these cases. PMID- 11774277 TI - Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1. AB - Intrinsic or acquired resistance to chemotherapy is responsible for failure of current treatment regimens in breast cancer patients. The Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major role in the development of a multidrug-resistant tumor phenotype. In human breast cancer, overexpression and nuclear localization of YB-1 is associated with upregulation of P-glycoprotein. In our pilot study, we analyzed the clinical relevance of YB-1 expression in breast cancer (n = 83) after a median follow-up of 61 months and compared it with tumor-biologic factors already used for clinical risk-group discrimination, i.e., HER2, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1). High YB-1 expression in tumor tissue and surrounding benign breast epithelial cells was significantly associated with poor patient outcome. In patients who received postoperative chemotherapy, the 5-year relapse rate was 66% in patients with high YB-1 expression. In contrast, in patients with low YB-1 expressions, no relapse has been observed so far. YB-1 expression thus indicates clinical drug resistance in breast cancer. Moreover, YB-1 correlates with breast cancer aggressiveness: in patients not treated with postoperative chemotherapy, those with low YB-1 expression are still free of disease, whereas the 5-year relapse rate in those with high YB-1 was 30%. There was no significant correlation between YB-1 expression and either HER2 expression or uPA and PAI-1 levels. Risk-group assessment achieved by YB-1 differed significantly from that by HER2 or uPA/PAI 1. In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making. PMID- 11774278 TI - Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT 1080 cells. AB - Collagenase-3 (MMP-13) is characterized by an exceptionally wide substrate specificity and restricted expression. MMP-13 is 1 of the few MMPs primarily expressed by tumor cells in malignant tumors, e.g., squamous cell carcinomas and its expression correlates with their invasion capacity. In this work, we have constructed an expression vector and a recombinant adenovirus harboring human MMP 13 cDNA to investigate the role of MMP-13 in cancer cell invasion. Our results show that constitutive expression of MMP-13 by HT-1080 cells stably transfected with MMP-13 expression vector or transduced with MMP-13 adenovirus markedly increased their invasion both through type I collagen and reconstituted basement membrane (Matrigel) with no alterations in expression or activation of collagenase-1 (MMP-1), gelatinase-A (MMP-2), or gelatinase-B (MMP-9). The enhanced invasion capacity of MMP-13 expressing HT-1080 cells was dependent on MMP activity, as it was blocked by MMP inhibitor Batimastat (BB-94) and tissue inhibitor of metalloproteinases-3 (TIMP-3). Our data provide direct evidence for the role of MMP-13 as a potent invasion proteinase, which alone can enhance the ability of malignant cells to penetrate through both basement membrane and fibrillar collagen. PMID- 11774279 TI - Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. AB - FK228 (formerly FR901228) was recently isolated from Chromobacterium violaceum as a potent antitumor agent and its biologic target protein was identified as histone deacetylase (HDAC). Because of its unique chemical structure (i.e., bicyclic depsipeptide) and activity profile in the National Cancer Institute's developmental therapeutics program, FK228 is currently in a phase I clinical trial for cancer therapy. In the present study, we investigated the antiangiogenic activity of FK228 in vivo and in vitro. FK228 potently blocked the hypoxia-stimulated proliferation, invasion, migration, adhesion and tube formation of bovine aortic endothelial cells at the same concentration at which the agent inhibited the HDAC activity of cells. In addition, FK228 inhibited the neovascularization of chick embryo and that of adult mice in the Matrigel plug assay. Interestingly, the expression of angiogenic-stimulating factors such as vascular endothelial growth factor or kinase insert domain receptor were suppressed by FK228, whereas that of angiogenic-inhibiting factors such as von Hippel Lindau and neurofibromin2 were induced, suggesting that a gene transcription effect was involved in the inhibition of angiogenesis by FK228. These results indicate that FK228 is a novel antiangiogenic agent and may suppress tumor expansion, at least in part, by the inhibition of neovascularization. PMID- 11774280 TI - Involvement of nucleophosmin/B23 in the response of HeLa cells to UV irradiation. AB - The steady-state mRNA level of nucleophosmin/B23 in HeLa cells increased after UV irradiation. Nucleophosmin/B23 antisense transfection potentiated ultraviolet (UV)-induced cell killing. A block in G(2)/M phase, larger peak of apoptotic cells and higher caspase-3 in vitro activity were noted in nucleophosmin/B23 antisense-transfected cells compared with vector-transfected cells after UV treatment. Irradiated cells that received vector plasmid exhibited increased levels of [(3)H]thymidine incorporation due to DNA repair synthesis. In contrast, irradiated cells that received nucleophosmin/B23 antisense plasmid exhibited no such increase of [(3)H]thymidine incorporation, indicating inhibition of DNA repair. Cotransfection of cells with vector allowed repair of the damaged chloramphenicol acetyl transferase (CAT) reporter and rescue of CAT activity by host repair machinery. CAT activity in cells cotransfected with nucleophosmin/B23 antisense was less (<50%) than that of vector-transfected cells, indicating reduction of host nucleotide excision repair activity. Lower protein expressions of nucleophosmin/B23 and proliferating cell nuclear antigen (PCNA) were observed in nucleophosmin/B23 antisense-transfected cells compared with vector-transfected cells with or without UV treatment. Cotransfection of nucleophosmin/B23 antisense transfected HeLa cells with PCNA construct made the cells less susceptible to UV induced cell killing. Our results indicate that nucleophosmin/B23 correlates with PCNA and DNA repair capacity in cellular sensitivity to UV. PMID- 11774281 TI - Resistance to tamoxifen-induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer. AB - Overexpression of Her2/neu is implicated in the development of resistance to the antiestrogen tamoxifen (TAM) that exerts its inhibitory effect through interaction with estrogen receptor (ER). Whereas Her2/neu and ER are believed to be important cell survival/death factors in human breast cancer cells, if and how they interact to confer resistance to hormone therapy is not known. This prompted us to investigate whether modulation of the effect of TAM occurs via the Her2/neu pathway and whether targeting the interaction between the Her2/neu pathway and the ER pathway is beneficial. There are 2 forms of ER that are localized to the cell membrane and to the nucleus. For the first time, we found that Her2/neu directly interacts with ER at the cell membrane. We then investigated the role of Her2/neu overexpression in the regulation of the cell membrane ER pathway in TAM resistant breast cancer cells and the nature of this interaction in apoptotic signaling. Relief of TAM resistance was associated with Her2/neu downregulation and ER upregulation. TAM-induced apoptosis occurred immediately after dissociation of Her2/neu from cell membrane ER. These results demonstrate a novel mechanism by which Her2/neu regulates the cell membrane ER-coupled apoptosis and the possible involvement of the Her2/neu in TAM resistance of breast cancer cells. Moreover, the antiproliferative activity of TAM should rely on the integration between the signal transduction from the cell membrane ER and the gene regulation by the nuclear ER. Coordinated modulation on the cell membrane ER/Her2/neu pathway and the nuclear ER/RAR pathway may provide a new approach for treatment of ER-positive, Her2/neu overexpressing breast cancer. PMID- 11774282 TI - Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth. AB - Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are well-known factors that induce neovascularization in many tumors. The molecular mechanisms that regulate tumor angiogenesis in human chondrosarcoma are not clear. We assessed in this work the angiogenic activities of a human chondrosarcoma cell line (OUMS-27) in vivo and determined the efficacies of angiogenic factors derived from OUMS-27 cells on human umbilical vein endothelial cells (HUVECs) in vitro. Tumor xenografts induced an increase in the formation of neovessels, but the distributions of Ki-67 antigen, VEGF and bFGF were unaffected. We also demonstrated that OUMS-27 cells secreted VEGF(165) into the culture medium and that it was the maximal angiogenic factor to stimulate endothelial proliferation and migration in chondrosarcoma. Anti-VEGF antibodies induced an approximately 70% inhibition of these responses of HUVECs, but did not have any effect on OUMS-27 cells. Anti-bFGF antibodies suppressed not only the activities of HUVECs but also the growth of tumor cells in vitro. We indicate that angiogenesis is principally elicited by VEGF(165) and that tumorigenesis is mainly regulated by bFGF stored in the extracellular matrix of OUMS-27 cells. The present study may offer the availability of combination therapies for inhibition of VEGF and bFGF action on vascular endothelial cells and chondrosarcoma cells, respectively. PMID- 11774283 TI - Prostasin serine protease inhibits breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation. AB - We have shown that prostasin serine protease is downregulated in high-grade prostate tumors and inhibits invasiveness of prostate cancer cell lines upon enforced reexpression. In our study, prostasin mRNA and protein were shown to be expressed in normal human mammary epithelial cells (NHMEC), the poorly invasive breast carcinoma cell line MCF-7 and the nonmetastatic breast carcinoma cell line MDA-MB-453, but absent in highly invasive and metastatic breast carcinoma cell lines MDA-MB-231 and MDA-MB-435s. Enforced reexpression of prostasin in MDA-MB 231 and MDA-MB-435s reduced the in vitro invasiveness of either cell line by 50%. Examination of the prostasin gene promoter and first exon revealed a GC-enriched region that contains transcription regulatory elements. The promoter and exon 1 region of the prostasin gene was investigated for DNA methylation in NHMEC and the carcinoma cell lines. The results revealed a methylation pattern that correlates with prostasin expression in these cells. Demethylation coupled with histone deacetylase inhibition resulted in reactivated expression of the prostasin mRNA in MDA-MB-231 and MDA-MB-435s cells. These results suggest that prostasin expression in breast cancer cells may be regulated by DNA methylation and that an absence of prostasin expression may contribute to breast cancer invasiveness and metastatic potential. PMID- 11774284 TI - Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration. AB - We demonstrated previously that rat ascites hepatoma MM1 cells require both lysophosphatidic acid (LPA) and fibronectin (FN) for phagokinetic motility and transcellular migration and that these events are regulated through the RhoA-ROCK pathway. It remains to be elucidated, however, how the signals from both LPA and FN are integrated into cell migration. To examine this, total cellular lysates after stimulation with LPA or FN were subjected to time-course immunoblot analysis with anti-phosphotyrosine antibodies (Abs). Consequently, tyrosine phosphorylation of paxillin was obviously persistent after stimulation with FN + LPA as compared to after stimulation with either alone. Tyrosine-phosphorylated paxillin comprised 2 components; slowly and fast migrating ones. Immunoblotting of anti-paxillin immunoprecipitates with phosphorylation site-specific Abs revealed the following: tyrosine-phosphorylation was enhanced preferentially on a slowly migrating component after stimulation with FN + LPA; this component contained phosphorylation at both tyrosine residue (Y) 31 and Y118; and phosphorylation of paxillin at Y181 was constitutive and not augmented by stimulation with either FN or LPA. Amiloride, an inhibitor of the Na+/H+ antiporter downstream of ROCK, suppressed cell motility and correspondingly paxillin tyrosine-phosphorylation at both Y31 and Y118. Paxillin phosphorylation weakly induced by FN alone, insufficient for cell migration, was not inhibited by amiloride. These results demonstrate that LPA collaborates with FN for persistent tyrosine phosphorylation of paxillin at both Y31 and Y118, regulated by the Na+/H+ antiporter downstream of ROCK and that this phosphorylated paxillin is essential for MM1 cancer cell migration. PMID- 11774285 TI - CD151 enhances cell motility and metastasis of cancer cells in the presence of focal adhesion kinase. AB - We have examined the role of the protein CD151 in cell motility, invasion and metastasis of cancer cells by using CD151-overexpressing cells prepared by transfection of CD151 cDNA into three cancer cell lines established from different origins; a human colon cancer RPMI4788, a human glioblastoma A172 and a human fibrosarcoma HT1080. Invasion into Matrigel and cell motility of all 3 CD151-overexpressing cancer cells were enhanced significantly when compared to control parental cells. Pulmonary metastasis of 2 metastatic CD151-overexpressing cancer cell lines, RPMI4788/CD151 and HT1080/CD151, was higher than that of control parental cells and was markedly inhibited by anti-CD151 monoclonal antibody (MAb), SFA1.2B4. To examine whether focal adhesion kinase (FAK) is associated with promotion of cell motility and invasion of cancer cells through CD151, we transfected human CD151 cDNA into FAK (+/+) or FAK (-/-) fibroblasts that were isolated from embryos in FAK-deficient mice and compared invasion into Matrigel and cell motility between each CD151-transfected cells and controls. The invasion into Matrigel and cell motility of CD151-transfected FAK (+/+) fibroblasts increased significantly above those of parental cells and were inhibited by anti-CD151 MAb, whereas those of CD151-transfected FAK (-/-) fibroblasts were not enhanced at all and were not blocked by anti-CD151 MAb. These findings indicate that the CD151 molecule enhances cell motility, invasion and metastasis of cancer cells and that FAK is needed for these events through CD151. PMID- 11774286 TI - Significance of phosphotyrosine proteins, Bcl-2 and p53 for apoptosis in resting B-chronic lymphocytic leukemia (CLL) cells. AB - Signal transduction and apoptosis in B-cell chronic lymphocytic leukemia (CLL) cells with a post-germinal center (GC) phenotype were studied. Specific activation of the cells was induced by a combination of soluble anti-CD40 monoclonal antibody and interleukin-4 (CD40/IL-4) and nonspecific activation with a combination of phytohemagglutinin, phorbol-12-myristate-13-acetate and ionomycin (chemical mixture). Less than 5% of these leukemia cells entered the cell cycle after activation, as indicated by the number of cells in G0/G1 phase. The protein tyrosine phosphorylation pattern and expression of the Bcl-2 protein were specific in ex vivo CLL cells of each individual patient. Expression of the p53 protein was not detectable in these leukemia cells. Cross-linking of the CD40/IL-4 receptors on CLL cells significantly upregulated phosphotyrosine proteins and the p53 protein. In the presence of chemical mixture, downregulated phosphotyrosine proteins were detected. Alterations in Bcl-2 expression were independent of cross-linking with CD40/IL-4 or chemical mixture. A high frequency of apoptotic cells was detected in cells that had downregulated phosphotyrosine proteins and Bcl-2 protein. There was no correlation between induction of apoptosis and expression of p53 protein. Our results suggest that apoptosis in resting leukemia cells could occur prior to the cell cycle progression. Alterations in phosphotyrosine proteins and Bcl-2 but not p53 might play an important role in the regulation of apoptosis in resting G0/G1 memory post-GC B CLL cells. PMID- 11774287 TI - Replacement of N-terminal portions of TGF-alpha with corresponding heregulin sequences affects ligand-induced receptor signaling and intoxication of tumor cells by chimeric growth-factor toxins. AB - ErbB receptor tyrosine kinases play an important role in developmental processes and tumor formation. Their activity is regulated by a family of structurally related ligands that bind to distinct ErbB receptor subsets, with transforming growth factor (TGF)-alpha preferentially interacting with epidermal growth-factor receptor (EGFR) and heregulin (HRG)-beta1 recognizing ErbB3 and ErbB4. To investigate the contribution of N-terminal ligand sequences to binding specificity, we have constructed 2 chimeric growth factors termed H181T8 and H194T20, which contain N-terminal HRG-beta1 sequences linked to complementary fragments of TGF-alpha. For bacterial expression and analysis of cell binding, the chimeric ligands were genetically fused to truncated Pseudomonas exotoxin A (ETA). H181T8-ETA and H194T20-ETA toxins both were cytotoxic for human tumor cell lines overexpressing EGFR but did not significantly affect the growth of cells that express ErbB receptors other than EGFR. Binding of H181T8, which contains HRG-beta1 residues 177-181, induced rapid autophosphorylation of EGFR, but in contrast to a previously described chimeric ligand based on EGF was unable to activate other ErbB receptors. H194T20, which contains HRG-beta1 residues 177 194, despite specific binding to EGFR was unable to induce autophosphorylation of any of the ErbB family members. However, H194T20 enhanced and modified the activity of parental TGF-alpha and HRG-beta1 when these ligands were simultaneously present. Our results show that modification of the N-terminal TGF alpha sequence can have a significant effect on the signaling properties of the ligand and suggest that different EGF-like ligands can synergize in the activation of ErbB receptors. PMID- 11774288 TI - Mutational analysis of StAR gene in adrenal tumors. AB - Adrenal adenomas and carcinomas are mostly monoclonal, suggesting that a genetic alteration in a progenitor cell may contribute to their development. However, the molecular pathogenesis of these tumors still remains unclear. It has been already excluded that activating mutations of the ACTH receptor or of G protein stimulator alpha sub-units, affecting cAMP pathway, is involved in the tumorigenesis. Therefore, this work has been focused on post-transductional (ACTH) signal alterations and in particular on the mutational analysis of the Steroid Acute Regulatory protein (StAR) gene to verify whether somatic mutations or genomic polymorphisms of this gene may be correlated with adrenal tumorigenesis. Tissue DNA was extracted from 40 functional and non-functional adrenocortical tumors that were removed from patients aged between 17 and 72 years (mean 43 +/- 4). Blood DNA was obtained from 24 patients (aged between 26 and 70 years) affected by adrenal tumors and from 100 healthy subjects without radiological and clinical evidence of adrenal masses, aged between 25-35 years (90 Caucasians and 10 Africans). The DNA was used as the template for the amplification of the StAR gene using the polymerase chain reaction. The amplified DNA of each exon of the StAR gene was purified and sequenced in automatic sequenciator. With the exception of exon 5 showing in codon 203 an homozygous missense mutation, the sequence of the other exons of the StAR gene resulted normal in all tumors studied. The same homozygous mutation (Asp203Ala) was observed in the sequence of exon 5 performed on genomic DNA of the 24 affected patients and in the control subjects. The homozygosity of the mutation observed in all patients (either in tissue or blood samples) and in control subjects, independently of their ethnic origin, led us to suggest that the Asp203Ala cannot be considered as mutation or as polymorphism, but that it must be considered as a mistake in the sequence entered in the Genbank, which needs to be modified accordingly. These data, and those up to now reported in the literature, allow us to suggest that mutations of the gene coding for the protein involved in the initial step of the steroidogenesis could not be considered as a possible cause for the development of adrenal tumors. PMID- 11774289 TI - Removal of acetaldehyde from saliva by a slow-release buccal tablet of L cysteine. AB - High alcohol intake is an independent risk factor for upper gastrointestinal (GI) tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL(95%) 43%, 76%). Area under the curve (AUC(0-320min)) with the L-cysteine and placebo tablet were 54.3 +/- 11 microM x hr and 162 +/- 34.2 microM x hr (mean +/- SEM), respectively (p = 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals. PMID- 11774290 TI - Diet, reproductive factors and lung cancer risk among Chinese women in Singapore: evidence for a protective effect of soy in nonsmokers. AB - The factors associated with risk of lung cancer among nonsmokers have not been fully elucidated, but dietary factors have consistently been shown to play a role. Chinese women are unique in having a high incidence of lung cancer despite a low smoking prevalence. This population is also known to have a high intake of soy, a dietary source of phytoestrogens. We conducted a hospital-based case control study among Singapore Chinese women, comprising 303 cases and 765 age matched controls, of whom 176 cases and 663 controls were lifetime nonsmokers. Data on demographic background, reproductive factors and dietary intake of fruit, vegetables and soy foods were obtained by in-person interview. We observed an inverse association between intake of total, cruciferous and non-cruciferous vegetables and risk of lung cancer among smokers. Although smokers in the highest tertile of fruit intake also had a lower risk, this was not statistically significant. Higher intake of soy foods significantly reduced risk of lung cancer among lifetime nonsmokers, but not among smokers. When soy isoflavonoid intake in mg/week was computed based on frequency and portion size of intake of eight common local soy foods, the adjusted OR among nonsmokers for the highest tertile compared to the lowest was 0.56, 95% CI 0.37-0.85 (p for trend <0.01). Fruit intake was also significantly associated with reduced lung cancer risk among nonsmokers, but the effect was not significant after adjustment for soy intake. On the other hand, soy intake remained an independent predictor of risk after controlling for fruit intake. Reproductive effects were also primarily confined to lifetime nonsmokers, among whom having 3 or more livebirths (adjusted OR 0.65, 0.44-0.96) and a menstrual cycle length of more than 30 days (OR 0.46, 0.25-0.84) accorded a significantly reduced risk of lung cancer. Place of birth was significantly associated with risk among nonsmokers (OR 2.6, 1.7-3.9 for China born vs. local born) but not among smokers. When analysis was restricted to nonsmokers with adenocarcinomas, the dietary effects were consistent or enhanced. On stepwise regression, soy intake and cycle length emerged as the independent dietary and reproductive predictors of lung cancer risk in nonsmokers. These findings are consistent with other evidence suggesting an involvement of estrogen related pathways in lung cancer among non-smoking women. PMID- 11774291 TI - Incidence and mortality trends for prostate cancer in 5 French areas from 1982 to 1996. AB - After an increase in the 1980s, incidence and mortality for prostate cancer in North America or England and Wales started to decrease in the early 1990s. The reasons for this evolution are widely debated, notably the importance of early detection. This study describes trends of prostate cancer incidence and mortality in 5 areas in France, where practices of early detection for this cancer are widely used. The 5 French administrative areas, covered by a population-based registry, have a total population of approximately 1,700,000 men. Incidence data from these registries were studied for the period 1982-1995, and mortality data were provided by the Institut National de la Sante et de la Recherche Medicale (INSERM) for the period 1982-1996. Age-Period-Cohort models by Poisson regression were created to characterize these trends. Between 1982 and 1995, 14,699 cases of prostate cancer were registered by the 5 registries under consideration. After a little intensification of the increase in 1987, undoubtedly due to early detection (notably using Prostate-Specific Antigen), the trend of the incidence seems to reverse from 1993. Mortality increased monotonically from 1982-1990 by an average of 1.8% per year, before decreasing annually by an average of 3.3% until 1996. Poisson regressions indicated a period effect on both incidence and mortality data; a small, but significant, cohort effect exists for incidence evolution, showing that elements such as etiologic factors may have an influence. Until results of randomized studies on mass screening are available, the question of individual screening remains; improved knowledge of risk factors could be interesting. PMID- 11774292 TI - Should we start population screening for prostate cancer? Randomised trials are still needed. PMID- 11774293 TI - High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer. AB - Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI 1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI-2 and uPAR using specific enzyme-linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I-II (n = 188). This group had a median follow-up time of 6.8 years (range 0.7-9.9), and 23 progressions were observed. The 80(th) percentile for PAI-2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression free survival. The results were also compared with DNA ploidy status, S-phase fraction, uPA and PAI-1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI-2 level was associated with shorter progression-free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI-1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI-2 and PAI-1 levels in tumors revealed a small group of stage I-II patients with an accumulative progression rate of 50%. PMID- 11774294 TI - Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer. AB - MAb-PAM4 is an anti-MUC1 antibody that has been shown to be reactive with 85% of pancreatic adenocarcinomas with no reactivity with normal pancreas or other tissues. Initial clinical studies have shown excellent targeting with high tumor/nontumor ratios. Gemcitabine, an analog of deoxycytidine, is currently a frontline treatment for pancreatic cancer. Acting via a number of metabolic pathways, gemcitabine is also a powerful radiosensitizer. Combined-modality, chemo/radiosensitization with gemcitabine and low dose (131)I-PAM4 radioimmunotherapy was performed to determine if a more effective treatment procedure could be developed. Athymic nude mice bearing large (1 cm(3)) CaPan1 human pancreatic tumors were given a single treatment cycle consisting of gemcitabine, 333 mg/m(2) administered on Days 0, 3, 6, 9 and 12 by intraperitoneal injection, along with either 100 or 200 microCi, (131)I-PAM4 administered on Day 0 by intravenous injection. Gemcitabine did not interfere with the biodistribution of radiolabeled antibody. Specific tumor targeting was observed for (131)I-PAM4, with a tumor/blood radiation dose ratio of 2.6 over the first 14 days. Gemcitabine alone and low dose radioimmunotherapy alone, each had no affect upon tumor growth; no statistical differences were noted in comparison to the untreated group. When combined, however, a statistically significant (p = 0.0324), synergistic anti-tumor effect was observed. Median survival time doubled for the combined treatment regimen compared to single modality treatment groups. The combined treatment modality was well tolerated by the mice. Our data show that combined gemcitabine with radioimmunotherapy may provide an improved alternative for the treatment of pancreatic cancer, achieving successful anti tumor effects with low toxicity. PMID- 11774295 TI - Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. AB - Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play an important role in angiogenesis associated with tumor growth and metastasis. VEGF exerts its biologic activities through 2 transmembrane tyrosine kinase receptors: the fms-like tyrosine kinase receptor (Flt-1, or VEGFR1) and kinase insert domain-containing receptor (KDR or VEGFR2). We have previously produced a panel of antibodies directed against KDR from mice immunized with the recombinant form receptor. These antibodies efficiently neutralized VEGF-induced KDR activation and mitogenesis of human umbilical vascular endothelial cells (HUVEC). Murine antibodies, however, may not be suitable candidates for human therapy because of their propensity to elicit human anti-mouse antibody response. Here we isolated several high-affinity human Fab antibody fragments directed against KDR from an antibody phage display library constructed from the pooled B lymphocytes of nonimmunized healthy human donors. These human Fab fragments bind specifically to KDR with nanomolar affinity and block KDR/VEGF interaction with IC(50) of approximately 2-20 nM. Further, they effectively inhibit VEGF-stimulated mitogenesis of HUVEC and migration of human leukemia cells. Epitope mapping studies demonstrated that all neutralizing human antibodies bound the epitope(s) located within the first 3 N-terminal immunoglobulin-like domains of KDR, the same region that encompasses the binding site of VEGF. Our results suggest that these human anti-KDR antibodies may have potential application in the treatment of cancer and other diseases in which pathologic angiogenesis occurs. PMID- 11774297 TI - Effect of experimental parameters on the in vitro release kinetics of transforming growth factor beta1 from coral particles. AB - Coral bone graft substitutes have been supplemented in the past with growth factors to further enhance bone regeneration in defects. Little is known, however, on the dynamics of protein release from coral. Coral particles were studied for their ability to release transforming growth factor beta 1 (TGF beta1) in vitro, under different adsorption conditions. Adsorption of TGF-beta1 (0.05 microg/mL) on coral particles (<80 microm or 300-450 microm) after 24 h of incubation was high, regardless of conditions. TGF-beta1 release kinetics in an artificial bone fluid followed a specific profile: an initial 1-h protein burst, followed by a decreasing release during the next 24 h at which time the release increased again to reach a constant rate until the end of the 2-week study. The protein release rate appeared mainly to depend upon the diffusion of TGF-beta1. TGF-beta1 release from coral particles was enhanced in the presence of bovine serum albumin (BSA) compared to the release in the presence of gelatin, and was dependent on the pH of adsorption. The highest total TGF-beta1 release was obtained when adsorption occurred with BSA at pH 7.4 (82 +/- 3%), while the lowest release was observed when adsorption was done in the presence of gelatin at pH 11 (38 +/- 1%). TGF-beta1 release was also found to vary with particle size, higher release being obtained with the smaller particles. These results suggest that coral particles could be used as a delivery system for growth factors, and that the release rate may be modulated through modification of the adsorption conditions and coral particle size. PMID- 11774298 TI - Effect of initiation chemistry on the fracture toughness, fatigue strength, and residual monomer content of a novel high-viscosity, two-solution acrylic bone cement. AB - Porous-free, two-solution bone cements have been developed in our laboratory as an alternative to commercial powder/liquid formulations. Each pair of solutions consist of poly(methyl methacrylate) (PMMA) powder dissolved in methyl methacrylate (MMA) monomer, with benzoyl peroxide (BPO) added to one solution as the initiator and N,N-dimethyl-p-toluidine (DMPT) added to the other as the activator. When mixed, the solutions polymerize via a free radical reaction, which is governed by the concentrations of initiator and activator and their molar stoichiometry. Previous work by the authors has demonstrated that these two solution cement compositions are comparable to Simplex P bone cement in polymerization exotherm, setting time, and flexural mechanical properties. This study was designed to evaluate the effect of BPO and DMPT concentrations, along with their molar ratio, on the fracture toughness, fatigue strength, and residual monomer content of the experimental compositions. The results showed that fracture toughness and fatigue strength for the solution cements were comparable to Simplex P and were not significantly affected by the BPO concentration or the BPO:DMPT molar ratio; however, the highest DMPT concentration yielded significantly lower values for both variables. Residual monomer content was significantly affected by both the individual concentrations of BPO and DMPT and their molar ratios. The two-solution cements had significantly higher residual monomer contents versus Simplex P; however, this can be attributed to their higher initial monomer concentration rather than a lower degree of conversion. PMID- 11774299 TI - Adsorption and release properties of growth factors from biodegradable implants. AB - The present investigation was performed to study the adsorption behavior of growth factors and their release characteristics from biodegradable implants in an in vitro study. We investigated the stability of growth factors administered on various scaffolds. We used porous tricalcium phosphate ceramics (alpha-TCP), a neutralized glass-ceramics (GB9N), a composite (polylactid/-glycolid/GB9N), and solvent dehydrated human bone as carriers. Block shaped scaffolds (sized: 7 x 7 x 10 mm) were loaded with 5 microg of either bone morphogenetic protein (rxBMP-4), basic fibroblast growth factor (rh-bFGF), or vascular endothelial growth factor (rh-VEGF) solved in 150 microL PBS. The growth factors were labeled with Iodine125 (I-125) for detecting the adsorbed and released amount of growth factors by counting the samples for total I-125 activity. We observed that the adsorption of these growth factors seems to depend on two different parameters: first on the nature of the tested material, and second on the growth factors on their own. The release kinetics of the growth factors from the biodegradable implants can be described as a two phase process-a very rapid release during the first hours by an elution of not adsorbed protein, followed by a specific release, which depends upon the chemical/physical interaction of the material and the growth factor used. Analyzing the eluted proteins on SDS-PAGEs rh-VEGF was degraded into a smaller fragment with a size of around 15 kDa, while rxBMP-4 and rh-bFGF showed a complete degradation into fragments smaller than 3 kDa after more than 3 days. Although this in vitro study suggests that biodegradable implants might be successfully used as carriers for osteogenic growth factors, the different release kinetics as well as the alteration of their molecular structure including loss of biological activity should be considered. PMID- 11774300 TI - Effect of poly(ethylene glycol) molecular weight on tensile and swelling properties of oligo(poly(ethylene glycol) fumarate) hydrogels for cartilage tissue engineering. AB - This study was designed to determine the effect of changes in poly(ethylene glycol) (PEG) molecular weight on swelling and mechanical properties of hydrogels made from a novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF), recently developed in our laboratory. Properties of hydrogels made from OPF with initial PEG molecular weights of 860, 3900, and 9300 were examined. The PEG 3900 formulation had a tensile modulus of 23.1 +/- 12.4 kPa and percent elongation at fracture of 53.2 +/- 13.7%; the PEG 9300 formulation had similar tensile properties (modulus: 16.5 +/- 4.6 kPa, elongation: 76.0 +/- 26.4%). However, the PEG 860 gels had a significantly higher modulus (89.5 +/- 50.7 kPa) and a significantly smaller percent elongation at fracture (30.1 +/- 6.4%), when compared with other formulations. Additionally, there were significant differences in percent swelling between each of the formulations. Molecular weight between crosslinks (M(c)) and mesh size were calculated for each OPF formulation. M(c) increased from 2010 +/- 116 g/mol with PEG 860 to 6250 +/- 280 g/mol with PEG 9300. Mesh size calculations showed a similar trend (76 +/- 2 A for PEG 860 to 160 +/- 6 A for PEG 9300). It was also found that these hydrogels could be laminated if a second layer was added before the first had completely crosslinked. Mechanical testing of these laminated gels revealed that the presence of an interfacial area did not significantly alter their tensile properties. These results suggest that the material properties of OPF-based hydrogels can be altered by changing the molecular weight of PEG used in synthesis and that multilayered OPF hydrogel constructs can be produced, with each layer having distinct mechanical properties. PMID- 11774301 TI - Control of wound infections using a bilayer chitosan wound dressing with sustainable antibiotic delivery. AB - A novel bilayer chitosan membrane was prepared by a combined wet/dry phase inversion method and evaluated as a wound dressing. This new type of bilayer chitosan wound dressing, consisting of a dense upper layer (skin layer) and a sponge-like lower layer (sublayer), is very suitable for use as a topical delivery of silver sulfadiazine (AgSD) for the control of wound infections. Physical characterization of the bilayer wound dressing showed that it has excellent oxygen permeability, that it controls the water vapor transmission rate, and that it promotes water uptake capability. AgSD dissolved from bilayer chitosan dressings to release silver and sulfadiazine. The release of sulfadiazine from the bilayer chitosan dressing displayed a burst release on the first day and then tapered off to a much slower release. However, the release of silver from the bilayer chitosan dressing displayed a slow release profile with a sustained increase of silver concentration. The cultures of Pseudomonas aeruginosa and Staphylococcus aureus in agar plates showed effective antimicrobial activity for 1 week. In vivo antibacterial tests confirmed that this wound dressing is effective for long-term inhibition of the growth of Pseudomonas aeruginosa and Staphylococcus aureus at an infected wound site. The results in this study indicate that the AgSD-incorporated bilayer chitosan wound dressing may be a material with potential antibacterial capability for the treatment of infected wounds. PMID- 11774302 TI - Biocompatibility of lipid-protein-sugar particles containing bupivacaine in the epineurium. AB - Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-microm median diameter) when used for sciatic nerve block in the rat. As a reference, we compared LPSPs to 60-microm median diameter poly(lactic-co-glycolic) acid (PLGA) microspheres (110,000 MW PLGA, glycolic/lactic ratio 65:35). Four days after injection, both particle types produced acute inflammation within the confines of the injectate, inflammation in adjacent tissues, and myotoxicity. Bupivacaine-free particles did not display myotoxicity, and inflammation in adjacent tissues was reduced. At 2 weeks, inflammation from LPSPs had almost disappeared, whereas PLGA microspheres had a foreign-body giant cell reaction until at least 8 weeks after injection. In contrast, 3.6-microm median diameter, 20,000-MW PLGA microspheres produced a primarily histiocytic reaction 2 weeks after injection. In summary, the LPSPs and PLGA microspheres studied herein have excellent biocompatibility, but tissue reaction to the former is of much shorter duration. Myotoxicity and inflammation of surrounding tissue is largely attributed to bupivacaine. Foreign-body giant cells may be attributed to particle size rather than a specific reaction to PLGA. PMID- 11774303 TI - Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells. AB - An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer. PMID- 11774304 TI - Localization of metallic ions with gingival fibroblast subcellular fractions. AB - Nickel-based alloys have been in use since the 1930s; however, there are concerns regarding the release of metal ions (Be(+2), Cr(+6), Cr(+3), Ni(+2), Mo(+6)) from these alloys into surrounding tissues. Therefore, the objective of this study was to determine the cellular location and accumulation of ions using atomic absorption spectroscopy and correlate location with the cytotoxic, morphologic, and ultrastructural evaluations reported previously. Human gingival fibroblasts were exposed to the metal ions for 72 h. Controlled atomic absorption spectroscopy studies were used to determine the intracellular location of these ions reported as parts per million metal ions per milligram protein. Enzymatic markers were shown to correspond to the appropriate fraction indicating success in fractionation of the gingival fibroblasts. These results correspond with the cytotoxic, morphologic, and ultrastructural alterations reported previously for fibroblasts exposed to these ions. The highest concentration of beryllium ions occurred in the low-density molecule fraction, where lipofuscin granules were found, which has been shown to contain metal ions. The highest concentrations of hexavalent chromium ions occurred in the plasma membrane and nuclear fractions followed by the mitochondria fraction, which is supported by the ions' ability to oxidize to trivalent chromium accumulating at the membrane as well as the alterations in nuclear and mitochondrial function. For trivalent chromium, the highest concentrations occurred in the low-density molecule and the plasma membrane fractions, which correlates with the ions' inability to readily cross membranes. The highest concentration of molybdenum ions occurred in the plasma membrane fraction correlating with alterations in membrane morphology and increased numbers of myelin figures. The highest concentration of nickel ions was associated with the cytosol fraction where lipid droplets seen in the transmission electron micrographs were located. The current study demonstrates that a successful subcellular fractionation was obtained on gingival fibroblasts and that the location of metallic ions within the fractions correlated with cellular alterations reported previously. PMID- 11774305 TI - Formation of apatite layers on modified canasite glass-ceramics in simulated body fluid. AB - Canasite glass-ceramics were modified by either increasing the concentration of calcium in the glass, or by the addition of P2O5. Samples of these novel materials were placed in simulated body fluid (SBF), along with a control material (commercial canasite), for periods ranging from 12 h to 28 days. After immersion, surface analysis was performed using thin film X-ray diffraction, Fourier transform infrared reflection spectroscopy, and scanning electron microscopy equipped with energy dispersive X-ray detectors. The concentrations of sodium, potassium, calcium, silicon, and phosphorus in the SBF solution were measured using inductively coupled plasma emission spectroscopy. No apatite was detected on the surface of commercial canasite, even after 28 days of immersion in SBF. A crystalline apatite layer was formed on the surface of a P2O5 containing canasite after 5 days, and after 3 days for calcium-enriched canasite. Ion release data suggested that the mechanism for apatite deposition was different for P2O5 and non-P2O5-containing glass-ceramics. PMID- 11774306 TI - Synthesis, degradation, and in vitro cell responses of sodium phosphate glasses for craniofacial bone repair. AB - This report outlines the initial synthesis, degradation, and short-term biocompatibility of sodium phosphate glasses, for use in the drawing of fibers and manufacture of biodegradable composites. Biocompatibility studies were performed using a macrophage cell line and primary human craniofacial osteoblasts. Sodium hydrogen phosphate and sodium dihydrogen phosphate glass synthesized for less than 1 h, resulted in a higher degradation rate than glass synthesized for 3 h or more (0.015 mg cm(-2) h(-1)). Glasses with high and low ratios of hydrogen phosphate to dihydrogen phosphate had very similar degradation rates. A condensation route for the formation of the glass should give rise to varying degradation rates with varying ratios of starting materials. It is suggested that the degradation rate of the glass is independent of the concentrations of the initial reagents and that ring-opening polymerization, which reaches an equilibrium state, occurs. Biocompatibility studies suggest minimal macrophage activation (low levels of peroxide and interleukin-1beta release and rounded morphology) and high osteoblast biocompatibility. The ultimate aim of our studies is to produce a biocompatible soluble phosphate glass that can be drawn into fibers for incorporation into a polycaprolactone matrix for craniofacial bone repair. This report demonstrates the successful production of a soluble glass, which is biocompatible with regard to osteoblasts and macrophages. Recent data from our laboratory have demonstrated successful fiber drawing and production of a novel polycaprolactone. PMID- 11774307 TI - Effects on articular cartilage of subchondral replacement with polymethylmethacrylate and calcium phosphate cement. AB - Bone defects were created in rabbit medial femoral condyle in a model where subchondral bone was completely removed or about 2 mm of subchondral bone was maintained. Groups without augmentation and augmented with autogenous bone, polymethylmethacrylate, or calcium phosphate cement were sacrificed at 3, 12, and 24 weeks for evaluation of articular cartilage and observation of bone formation. In the model in which subchondral bone was completely removed, collapse of the subchondral bone together with exfoliation and prolapse of cartilage developed early in all cases. In the model in which 2 mm of subchondral bone was maintained, degeneration of articular cartilage developed at 12 weeks in the group augmented with polymethylmethacrylate, showing a significant difference when compared to the contralateral untreated control group. The group augmented with calcium phosphate cement did not demonstrate any evident difference from the control group. Mechanical properties after subchondral replacement did not differ between the groups augmented with polymethylmethacrylate and calcium phosphate cement, although calcium phosphate cement was considered histologically superior. Calcium phosphate cement was a reliable subchondral replacement material when the bone defect is adjacent to the articular cartilage. PMID- 11774308 TI - Novel current-conducting composite substrates for exposing osteoblasts to alternating current stimulation. AB - The present study demonstrates that novel nanocomposites consisting of blends of polylactic acid and carbon nanotubes effectively can be used to expose cells to electrical stimulation. When osteoblasts cultured on the surfaces of these nanocomposites were exposed to electric stimulation (10 microA at 10 Hz) for 6 h/day for various periods of time, there was a 46% increase in cell proliferation after 2 days, a 307% increase in the concentration of extracellular calcium after 21 consecutive days, and upregulation of mRNA expression for collagen type-I after both 1 and 21 consecutive days. These results provide evidence that electrical stimulation delivered through novel, current-conducting polymer/nanophase composites promotes osteoblast functions that are responsible for the chemical composition of the organic and inorganic phases of bone. Furthermore, this evidence elucidates aspects of the cellular/molecular-level mechanisms involved in new bone formation under electrical stimulation. PMID- 11774309 TI - The effect of particle wear debris on NFkappaB activation and pro-inflammatory cytokine release in differentiated THP-1 cells. AB - Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. Previous in vitro studies have reported that particles of wear debris induce the release of pro inflammatory cytokines and other inflammatory mediators from macrophages and other cells. Several recent investigations, however, have suggested that the wear particles themselves may not be primarily responsible for the inflammatory cellular responses, but that the observed cytokine release in vitro may be caused by endotoxin adsorbed to commercially available particle preparations. The intracellular pathways involved in macrophage signal transduction also are poorly understood. The purposes of this study are to use isolated orthopedic wear debris particles to evaluate pro-inflammatory cytokine release and nuclear factor kappa B (NFkappaB) activation from macrophages. Cells from human monocyte/macrophage cell line (THP-1) were differentiated and incubated with particles of debris that had been isolated from a failed human total hip arthroplasty. The titanium-alloy particles did not evoke release of TNF-alpha or IL-1beta whereas lipopolysaccharide (LPS) or LPS-treated debris particles induced both TNF-alpha and IL-1beta. LPS-treated particles, but not particles alone, stimulated NFkappaB activation. Our results suggest that at the concentrations tested in this study, endotoxin-free wear debris particles may not themselves initiate inflammatory cellular responses in differentiated THP-1 cells. It is unclear whether adsorbed endotoxin is clinically associated with osteolysis and/or loosening in total joint arthroplasties, but several factors, including adsorbed endotoxin, need to be investigated to explore the cellular responses responsible for osteolysis and/or loosening. PMID- 11774310 TI - Proliferation and differentiation of rat calvarial osteoblasts on type I collagen coated titanium alloy. AB - Several attempts have been made to improve osseointegration of titanium alloy as an implant material by modification of its surface. In the present study, proliferation, differentiation, and mineralization of osteoblasts on type I collagen-coated Ti6Al4V were investigated. The activity of alkaline phosphatase and the accumulation of calcium by osteoblasts grown on titanium alloy were significantly higher compared to cells grown on polystyrene. Precoating of the implant surface with type I collagen did not extensively affect proliferation, the activity of alkaline phosphatase, collagen synthesis, calcium accumulation, or the mRNA levels for collagen I alpha1, osteopontin, osteocalcin, MMP-2, and TIMP-2. Maximum collagen synthesis by osteoblasts was observed at day 4 of culture independent of the type of implant material. The specific activity of alkaline phosphatase reached its maximum at day 18 of culture. Accumulation of calcium and elevated mRNA levels for osteocalcin were found at day 22. These results indicate that collagen-coating alone is not sufficient to accelerate differentiation of rat calvarial osteoblasts on Ti6Al4V. PMID- 11774311 TI - Hypothermia-induced platelet aggregation in human blood in an in vitro model: the dominant role of blood-material interactions. AB - Hypothermia-induced platelet aggregation (HIPA) with or without neutrophil involvement may cause neurologic dysfunction during hypothermic surgery. We report the use of a previously developed model to study the contributions of several surfaces, surface area, shear rate, and blood-material exposure time to HIPA. Heparinized (1.5 u/mL) human blood was quenched to 24 degrees C and passed (0.5 mL/min) through a 75-cm long 1/32" ID tubing of polyvinylchloride (PVC), polyethylene (PE), polyurethane (PU), Teflon-FEP, or heparin (Duraflo)-coated PVC. The number of aggregates was measured by a light-scattering method, and the concentration of occlusive aggregates was assessed using constant-pressure filtration (50 mmHg). No differences were seen among PVC, PE, PU, or Teflon-FEP. The heparin-coated PVC tubing produced fewer occlusive aggregates, and heparin leaching from the coating was not the cause of the decrease in occlusive aggregates. Increasing surface area increased the number of aggregates, and increasing shear rates decreased the occlusiveness of those aggregates. PMID- 11774312 TI - Biomimetic calcium phosphate coatings on Polyactive 1000/70/30. AB - Precalcification of Polyactive 1000/70/30 with a biomimetic calcium phosphate coating is expected to enhance the bioactivity of this biodegradable polymer for the application as bone filler or scaffold of bone tissue engineering. This study presents a 1-day one-step incubation method to obtain either amorphous or bone like apatitic calcium phosphate coating on Polyactive 1000/70/30. Either dense plates or three-dimensional porous blocks of the polymer were incubated in a simplified but concentrated simulated body fluid-derived solution at 37 degrees C. By bubbling CO2 gas, a solution was prepared with calcium and phosphate ion concentrations five times of that of regular simulated body fluid. With controlled stirring, the CO2 was released out of the solution and exchanged by air. The pH of the solution increased to induce coating formation. Adjusting stirring rate and CO2/air exchange rate controlled the process kinetics. The reaction kinetics had little influence on the crystallographic structure of the final coating mineral for a given solution composition as shown by Fourier transform infrared spectroscopy and X-ray diffraction. However, the interface structure between the coating and substrate was kinetics-dependent. A fast precipitation condition resulted in a uniform but superficial calcification pattern at the surface of polymer. A slow process by selecting either a slow stirring or a slow CO2/air exchange, on the contrary, induced a localized but deep inside calcification pattern. A tensile test showed no statistically significant difference in the mechanical properties among uncoated and coated polymers. The cracking behavior of coatings from different kinetics, however, exhibited different manners, as can be attributed to different interface structures and interfacial strengths. PMID- 11774313 TI - Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model. AB - The treatment of large cranial defects may be greatly improved by the development of precisely formed bone tissue engineering scaffolds. Such scaffolds could be constructed by using UV laser stereolithography to photocrosslink a linear, biodegradable polymer into a three-dimensional implant. We have previously presented a method to photocrosslink the biodegradable polyester, poly(propylene fumarate) (PPF). To ensure the safety and effectiveness of this technique, the soft and hard tissue response to photocrosslinked PPF scaffolds of different pore morphologies was investigated. Four classes of photocrosslinked PPF scaffolds, constructed with differing porosities (57-75%) and pore sizes (300-500 or 600-800 microm), were implanted both subcutaneously and in 6.3-mm-diameter cranial defects in a rabbit model. The rabbits were sacrificed at 2 and 8 weeks, and the implants were analyzed by light microscopy, histological scoring analysis, and histomorphometric analysis. Results showed the PPF scaffolds elicit a mild tissue response in both soft and hard tissues. Inflammatory cells, vascularization, and connective tissue were observed at 2 weeks; a decrease in inflammatory cell density and a more organized connective tissue were observed at 8 weeks. Scaffold porosity and scaffold pore size were not found to significantly affect the observed tissue response. Evidence of scaffold surface degradation was noted both by histology and histomorphometric analysis. Bone ingrowth in PPF scaffolds implanted into cranial defects was <3% of the defect area. The results indicate that photocrosslinked PPF scaffolds are biocompatible in both soft and hard tissues and thus may be an attractive platform for bone tissue engineering. PMID- 11774314 TI - In catheter infections by Staphylococcus epidermidis the intercellular adhesion (ica) locus is a molecular marker of the virulent slime-producing strains. AB - Recently, it has been shown that S. epidermidis includes the ica operon responsible for slime production. In the operon, coexpression of icaA and icaD genes is required for full slime synthesis. In this study, the presence of icaA and icaD genes was searched for in a collection of 100 Staphylococcus epidermidis strains from catheter-associated infections by an original PCR method. Another 51 strains of S. epidermidis isolated from the skin or mucosa of healthy volunteers (26 of which derived from the hospital staff) were also investigated. Slime forming ability was phenotypically tested on Congo red agar plates. Sixty-one percent of the strains isolated from catheters were icaA- icaD-positive and produced slime. The results indicate that detection of ica genes by a PCR method is a useful tool for prompt identification of S. epidermidis slime-forming strains isolated from catheter-related infections. Also, three saprophytic strains from the hospital staff were positive for slime synthesis and presence of ica genes, suggesting a potential diffusion of slime-forming strains in hospital personnel. PMID- 11774315 TI - Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems. AB - The present studies describe the fabrication and characterization of highly porous and interconnected poly(alpha-hydroxy acid) foam scaffolds produced using a phase separation multisolvent system, followed by a sublimation process. Fabrication parameters, including solvent composition, polymer concentration, freezing temperature, polymer type, and polymer molecular weight, were optimized to produce the desired foam microstructure. Analyses of selected samples with scanning electron microscopic images and mercury intrusion porosimetry indicated polymer foams with pore size ranges of 100-350 microm, a porosity >90%, and an interconnecting open-pore foam structure. Scaffold degradation profiles varied according to the type and molecular weight of the polymers. Cytocompatibility assays demonstrated that the preferred foam structures were nontoxic and osteoprecursor cells seeded into the scaffolds exhibited the ability to attach, propagate, and differentiate into a calcified structure. PMID- 11774316 TI - Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro. AB - Bone morphogenetic protein-2 (BMP-2) delivered in a suitable implantable matrix has the potential to repair local skeletal defects by inducing new bone formation from undifferentiated pluripotent stem cells resident in host tissue. In this study, we examined in vitro the potential of a derivatized hyaluronic acid (Hyaff 11) scaffold as a delivery vehicle for recombinant human BMP-2 (rhBMP-2) in bone and cartilage repair therapies. Hyaff-11 scaffolds were fabricated using a phase inversion/particulate leaching method and soak-loaded with rhBMP-2. In vitro release kinetics of rhBMP-2, demonstrated using enzyme-linked immunosorbant assay and alkaline phosphatase (ALP) assay revealed a slow, sustained rhBMP-2 release during 28 days, with a cumulative release of 31.82% of the initial rhBMP-2 loaded. rhBMP-2 was released in bioactive form as demonstrated by ALP induction of pluripotent cell line, C3H10T1/2 (T1/2), down the osteoblast lineage when incubated with the release supernatants. rhBMP-2 retention in Hyaff-11 scaffolds was greater than that from collagen gels, which released most of the initially loaded rhBMP-2 by 14 days. rhBMP-2-loaded Hyaff-11 scaffolds were also seeded with T1/2 cells and evaluated at 3, 7, 14, and 28 days for viability and expression of osteoblast phenotype. Cells remained viable throughout the study and expressed a time- and dose-dependent ALP and osteocalcin expression in the rhBMP-2 groups. Based on these observations, Hyaff-11 scaffolds may be suitable delivery systems for rhBMP-2 in bone/cartilage repair because of their ability to retain rhBMP-2, release low levels of bioactive rhBMP-2 to the local environment in a sustained manner, and stimulate differentiation of pluripotent stem cells. PMID- 11774317 TI - Evaluation of the biocompatibility of a chitosan scaffold in mice. AB - Chitosan scaffolds appear to be suitable for a variety of tissue engineering applications. This study addressed the biocompatibility of chitosan in a mouse implantation model. Porous chitosan scaffolds were implanted in mice, and animals were sacrificed after 1, 2, 4, 8, or 12 weeks. Macroscopic inspection of the implantation site revealed no pathological inflammatory responses. Histological assessment indicated marked neutrophil accumulation within the implant, which resolved with increasing implantation time. Gram staining and limulus assays revealed no evidence of infection or endotoxin. Collagen was observed within the chitosan pore spaces, indicating that connective tissue matrix was deposited within the implant. Angiogenic activity associated with the external implant surface was also observed. Cellular immune responses were determined by lymphocyte proliferation assays, and antibody responses were measured using ELISA techniques. These assays indicated a very low incidence of chitosan-specific reactions. Although there was a large migration of neutrophils into the implantation area, there were minimal signs of any inflammatory reaction to the material itself. This preliminary study demonstrates that chitosan has a high degree of biocompatibility in this animal model. Overall, the findings suggest that chitosan may be suitable for the development of implantable materials. PMID- 11774318 TI - Probe of specific interaction between a simplified synthetic glycopolymer and erythrocytes as mediated by a glucose transporter (GLUT) on a cell membrane. AB - In order to develop a biomimetic polymer for cell recognition, we synthesized poly [3-O-(4'-vinylbenzyl)-D-glucose] (PVG), a polystyrene derivative with reduced glucose moiety, and studied the specific interaction of this PVG with erythrocytes, carried by a glucose transporter (GLUT-1), on a cell membrane. To clarify the specific interaction between the PVG and the erythrocytes, fluorescein isothiocyanate- (FITC) labeled polymer was used to prove and visualize the specific interaction. We found that labeled polymer strongly binds to erythrocytes, probably due to the specific interaction mediated by the presence of GLUT-1 on the cell membrane. The fluorescence intensity of PVG on erythrocytes was time and dose dependent. To verify the specific interaction between the PVG and the erythrocytes, cells were pretreated with phloretin, an inhibitor of GLUT-1, before adding the FITC-labeled PVG polymer to the cell culture medium. This treatment suppressed the interaction of PVG with erythrocytes. A confocal laser microscopic study further confirmed this interaction. The results from this study provide evidence that a biomimetic polymer of PVG interacts with erythrocytes mediated by GLUT-1 on cell membranes. PMID- 11774320 TI - Silica- and zirconia-hybridized amorphous calcium phosphate: effect on transformation to hydroxyapatite. AB - The goal of this study was to determine the effect that silica and zirconia have on the stability of bioactive amorphous calcium phosphate (ACP) mineral, i.e., in retarding its transformation to hydroxyapatite (HAP). The glass-forming agents, tetraethoxysilane and zirconyl chloride, were introduced individually during the low-temperature preparation of ACP. These hybrid ACPs (Si-ACP and Zr-ACP, respectively) as well as the control, unhybridized ACP (u-ACP), were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, specific surface area measurements, and chemical analysis (Ca/PO(4) ratio of the solids) before being dispersed in one of the following four test solutions: N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered (pH = 7.40) saline solutions with 0 microg/g fluoride (test solution A1), 1 microg/g fluoride (test solution A2), and 10 microg/g fluoride (test solution A3), or a lactic acid-containing solution (pH = 5.10, adjusted with NaOH; test solution B). Aliquots were taken at predetermined time intervals for solution Ca and PO(4) analysis. Solids isolated after 30 and 90 min exposure to solution B as well as the final dissolution/transformation products from all four solution experiments were analyzed by Fourier transform infrared spectroscopy and X-ray diffraction. Regardless of the type of experimental solution used, slower conversion to HAP was observed with the hybrid ACPs compared with u-ACP. The retarding effect of the Si or Zr species in the hybridized ACPs is probably due to these ions specifically blocking, by adsorption, potential sites for HAP nucleation and growth. The stability of ACP toward HAP conversion increased in the following order: u-ACP < Si-ACP < Zr-ACP. Hybrid ACP fillers, especially Zr-ACP, could be utilized in applications in which it is desired to enhance performance of composites, sealants, and/or adhesives in preventing demineralization or actively promoting remineralization. PMID- 11774321 TI - Prosthetic metals have a variable necrotic threshold in human fibroblasts: an in vitro study. AB - The generation of metal particles from prosthetic joints has been an evolving problem in orthopedics. Numerous factors have been involved including cells, metals, and responding cytokines, but determining roles of these factors or cascades of factors has been elusive. This laboratory has published threshold levels for commercially pure titanium (CpTi), which led to cell necrosis, but noted that cell viability differed among donor patients. To compliment the previous work we examined two other metals, Tantalum (Ta) and cobalt-chrome (CoCr), while making comparative measurements in these different donor patients. Retrieved human fibroblasts (superior medial plica) were cultured in a standard manner and exposed to various dosages of the three metals. Cell counts and interleukin (IL) 6 were used as dependent variables within a three-way analysis of variance. The data show that fibroblast necrosis was significantly affected by both type and mass of metal, with each metal having a distinct threshold (CpTi most necrotic, followed by Ta and CoCr). The cell counts and IL-6 at control levels varied significantly among all three donors. However, the response to the metals and dosages did not differ among tissue donors. Thus, although each patient had a different starting value for cell counts and IL-6, they responded to the metal particles in the same proportionate manner. PMID- 11774322 TI - Biocompatibility studies on biodegradable polyester-based composites of human osteoblasts: a preliminary screening. AB - A series of biodegradable composites with natural hydroxyapatite, designed for possible use in orthopedics applications, were preliminarily screened for biocompatibility by employing primary cultures of human osteoblasts in a direct contact method. The cells were seeded at low density onto the materials under investigation and allowed to grow for 2 weeks. They then were analyzed for morphology, proliferation, viability, alkaline phosphatase activity (AP), osteocalcin (OC) production, and extracellular matrix mineralization. The results showed that all materials have good biocompatibility. Cell viability tests demonstrated that in all cases the values were comparable to the control, and the addition of hydroxyapatite always resulted in an enhancement of performance with respect to the plain polymer. AP and OC analysis confirmed that all composites allowed the expression of phenotypic markers. Scanning electron microscopy provided direct evidence of intense cell adhesion and proliferation on the tested materials. PMID- 11774323 TI - Sterically blocking adhesion of cells to biological surfaces with a surface active copolymer containing poly(ethylene glycol) and phenylboronic acid. AB - Graft copolymers were designed that could spontaneously bind to biological surfaces and block subsequent recognition and adhesion at those surfaces. Phenylboronic acid (PBA) moieties in the polymer backbone provided binding to surfaces, forming reversible covalent complexes with cis-diols found in many biological molecules. Pendant poly(ethylene glycol) (PEG) side chains sterically protected those surfaces from subsequent interactions with other proteins and cells. The PEG and PBA grafting ratios on these poly-L-lysine-graft-(PEG;PBA) copolymers [PLL-g-(PEG;PBA)] were varied, and the polymers were tested in models relevant to undesirable wound-healing responses such as peritoneal adhesion formation and posterior capsule opacification. PLL-g-(PEG;PBA) polymers spontaneously coated tissue culture polystyrene and completely blocked rabbit lens epithelial cell adhesion to the surface over a wide range of PEG grafting ratios. PLL-g-(PEG;PBA)s with optimal grafting ratios were able to coat adsorbed serum proteins or extracellular matrices and block cell spreading on the surfaces at 4 h, although the effect was lost within 24 h. The polymer also enhanced the efficacy of surgical lysis of peritoneal adhesions in rats. The reversible covalent complexes formed by the PBA moieties on the copolymer backbone were more effective at binding biological surfaces than electrostatic interactions formed via a copolymer lacking the PBA moieties, that is, PLL-g-PEG. PMID- 11774325 TI - Cells, rather than extracellular matrix, nucleate apatite in glutaraldehyde treated vascular tissue. AB - Glutaraldehyde (GA) causes a large increase in [Ca(2+)](i) and [P(i)](i) and calcification of porcine aortic valve fibroblasts. Calcification in GA-treated vascular tissue is likely to begin intracellularly, but the potential role of extracellular matrix has not been taken into account in earlier studies. To compare the role of cells and matrix in calcification, intestinal pouches made of a lipid-extracted rat small intestine were prepared. Lipid-extracted porcine aortic valves, or cells cultured from those same valves, were placed in intestinal pouches, sealed, fixed with GA, and grafted in rat subcutis. Cells in the pouches calcified in 3 weeks whereas the valvular matrix did not calcify for 9 weeks. Cellular calcification spread to the wall of the intestinal pouches and grew heavier after 9 weeks. Similarly, smooth muscle cells calcified exclusively in GA-treated rat aorta grafted in rat subcutis for 3 weeks. Calcification of extracellular matrix was seen after 9 weeks. Cells initiate calcification and extracellular matrix serves as a substrate for the subsequent growth of apatite in GA-treated vascular tissue. PMID- 11774324 TI - Low pressure plasma treatment of poly(3-hydroxybutyrate): toward tailored polymer surfaces for tissue engineering scaffolds. AB - Thin films of poly(3-hydroxybutyrate) were modified by microwave ammonia plasma treatment. The results of the modification were studied by means of contact angle goniometry, ellipsometry, Fourier transform infrared-attenuated total reflection spectroscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. To prove the presence of amino groups on the poly(3-hydroxybutyrate) surface, chemical labeling with 4-trifluoromethyl benzaldehyde was performed before X-ray photoelectron spectroscopy analysis. Under the applied plasma conditions, a hydrophilic surface with a good long-term stability was obtained. PMID- 11774326 TI - The relationship between stress, porosity, and nonlinear damage accumulation in acrylic bone cement. AB - The long-term survival of cemented hip replacements depends on the ability of the cemented fixation to resist fatigue damage. Damage has been assumed to accumulate linearly (Miner's law) even though it is unlikely to be the case in such a porous brittle material. This study addresses the nonlinear stress-dependent nature of fatigue damage accumulation in acrylic bone cement. Specimens were subjected to a zero-to-tension fatigue load in water at 37 degrees C. A total of 15 specimens were tested, i.e., five specimens at each of three stress levels. The specimens were cyclically loaded to a certain fraction of their fatigue lives and the amount of microcracking present at that time was quantified by counting each crack and measuring its length. This procedure was repeated until the specimen failed. A total of 801 cracks formed in the 15 specimens. All cracks were found to initiate at pores. Crack propagation directions were distributed normally about the direction perpendicular to the applied load at the lower stress levels, but at higher stress, the distribution tended to be broader. At higher stresses, more cracks were produced per pore. The damage accumulation process in acrylic bone cement was found to be nonlinear with the degree of nonlinearity increasing with stress. Furthermore, great variability was found which was attributed to the differences in porosity between specimens. A power law equation is given which describes the predicted relationship between damage accumulation and number of loading cycles as a function of the stress level. PMID- 11774327 TI - Electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy analysis of titanium surfaces cultured with osteoblast-like cells derived from human mandibular bone. AB - Variations in the oxide films on titanium surfaces blasted with TiO(2) particles of various sizes were analyzed after cultures with cells derived from human mandibular bone. Turned titanium surfaces and surfaces blasted with 63-90-, 106 180-, and 180-300-microm TiO(2) particles were cultured with osteoblast-like cells. The surfaces were characterized before and after the cell culture with electrochemical impedance spectroscopy (EIS). The surface chemical composition of selected samples was analyzed with X-ray photoelectron spectroscopy (XPS). EIS revealed that with respect to the turned surfaces, the effective surface area was about 5, 6, and 4 times larger on the surfaces blasted with 63-90-, 106-180-, and 180-300-microm particles, respectively. After 28 days of the cell culture, the corrosion resistance on all sample types was unaffected. The impedance characteristics suggest a considerable effect of ion incorporation and precipitation during culturing. XPS revealed that before the cell culture, a typical surface layer consisted of TiO(2). After the culture, the surface oxide film contained both phosphorus and calcium, along with large amounts of oxidized carbon (carbonate) and nitrogen. There were lower concentrations of carbon and nitrogen on the blasted surfaces. We concluded that the effective surface area was several times higher on blasted surfaces than on turned surfaces. Cells derived from human mandibular bone affected ion incorporation into the implant surface. PMID- 11774328 TI - Effect of adsorbed fibronectin concentration on cell adhesion and deformation under shear on hydrophobic surfaces. AB - To facilitate tissue integration with biomaterials proteins and peptides frequently are immobilized on the biomaterial surface. In particular, extracellular matrix proteins--which interact specifically with integrin adhesion receptors on the cell surface--can stimulate initial cell attachment by serving both as a ligand for receptor-mediated attachment and as a stimulant of focal adhesion formation and cytoskeletal reorganization. Consequently, the strength of cell adhesion should depend both on the strength of cell/surface contacts and cytoskeleton-dependent properties of the cell (i.e., morphology, compliance). To examine this dual role of extracellular matrix proteins, murine fibroblasts were seeded onto self-assembled monolayers (SAMs) of dodecanethiolate coated with 0 to 0.45 microg/cm(2) of fibronectin (Fn) and then detached by hydrodynamic shear using a radial-flow chamber (RFC). Cell adhesion was characterized in terms of the critical wall shear stress for detachment (tau(wc)), and the compliance was evaluated from measurements of cell displacement and elongation as a function of the fibronectin concentration. Critical wall shear stress and cell displacement were found to be insensitive to Fn at concentrations below 0.23 microg/cm(2) while above this threshold tau(wc) increased and displacement decreased with increasing Fn concentration. Elongation of the cells in the direction of flow was independent of Fn concentration, but correlated linearly with tau(wc) for Fn densities below 0.23 microg/cm(2). These studies show that Fn concentration affects both tau(wc) and cell displacement under shear, and that tau(wc) is sensitive to cell compliance. In addition, they suggest that the dominant mechanism of cell detachment from hydrophobic substrates involves cell displacement. PMID- 11774329 TI - Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method. AB - This study developed a solvent merging/particulate leaching method for preparing three-dimensional porous scaffolds. Poly(L-lactic-co-glycolic acid) (PLGA) and sodium chloride particles were dry-mixed and cast into a special mold, through which a liquid could pass due to a pressure difference. An organic solvent was then poured into the mold to dissolve and merge the PLGA particles under negative pressure. A nonsolvent was conducted into the PLGA/salt composite to solidify and precipitate the merged PLGA matrix. Finally, a large amount of water was passed through the mold to leach out the salt particles so as to create a porous structure. The results revealed that a highly porous three-dimensional scaffold (>85 vol %) with a well interconnected porous structure could be achieved by this process. Porosity and the pore size of the scaffold were controlled using the ratio and the particle size of the added salt particles. A larger-volume scaffold was produced using a larger mold. This work provides a continuous and simple procedure for fabricating a bulk three-dimensional porous scaffold for tissue engineering. PMID- 11774330 TI - A comparative evaluation of the tissue responses associated with polymeric implants in the rat and mouse. AB - End product application is an important consideration when evaluating a material in an in vivo setting (Didisheim, Cardiovasc Pathol 1993;2:1S-2S). Small animal models allow high through-put evaluation of biocompatability. Previous preclinical evaluations have often used a rat subcutaneous model for the characterization of material-tissue interaction. Recent advances in genetic manipulation have provided mouse models with selective expression of a wide range of critical proteins. The rat model does not have many of the resources (i.e., knockouts, SCID, nude) that are present in mouse strains. The availability of these mice provides a resource to delineate the mechanisms regulating the healing associated with implants. However, before the mouse models can be used, they must be validated with respect to their ability to accurately assess tissue responses to materials. In this study the tissue responses after the implantation of expanded polytetrafluoroethylene (ePTFE) were compared between rat and mouse. Discs of ePTFE (30-microm internodal distance) were implanted in subcutaneous and epididymal fat tissue of rats (Sprague-Dawley) and mice (129-SVJ). After 5 weeks the samples were removed and evaluated for vascular density, inflammation, and fibrous encapsulation. No difference in the vessel density was observed within the peri-implant subcutaneous and adipose tissue or within the porous material. However, a significant difference was found in the number of activated macrophages and giant cells between these two species. Implants in the rat exhibited greater numbers of activated inflammatory cells in the peri-implant tissue. The data indicate that the mouse and rat provide a comparable model for evaluating angiogenesis and neovascularization associated with synthetic porous implants. PMID- 11774331 TI - Matrix engineering for osteogenic differentiation of rabbit periosteal cells using alpha-tricalcium phosphate particles in a three-dimensional fibrin culture. AB - Tissue engineering using periosteal cells is a promising approach for bioactive bone repair. Of central importance in tissue engineering is the cell-matrix interaction. In the present study we tested in vitro the influence of alpha tricalcium phosphate (alpha-TCP) particles on the expression of osteogenic markers in rabbit periosteal cells embedded in specially manufactured fibrin beads. After cell isolation from tibial periosteum of New Zealand White rabbits, and following monolayer culture, cells were embedded in alginate-fibrin beads containing 7.5% alpha-TCP particles and, as a control group, in beads without particles. The alginate was extracted immediately after polymerization. The beads were cultivated for at least 53 days. The DNA content, alkaline phosphatase activity, and osteocalcin level were determined. In monolayer culture the number of cells increased 6.5-fold. DNA content increased in both three-dimensional culture groups but was significantly higher in the beads containing alpha-TCP. Alkaline phosphatase activity increased in both groups without significant differences. Osteocalcin content was significantly higher in the beads containing alpha-TCP than it was in those without alpha-TCP. These observations indicate that matrix engineering using inorganic particles in fibrin culture can influence the osteogenic differentiation of mesenchymal cells. The three-dimensional culture system presented here facilitates the preparation of grafts for bone reconstruction. PMID- 11774332 TI - Novel synthesis and characterization of an AB-type carbonate-substituted hydroxyapatite. AB - A novel synthesis route has been developed to produce a high-purity mixed AB-type carbonate-substituted hydroxyapatite (CHA) with a carbonate content that is comparable to the type and level observed in bone mineral. This method involves the aqueous precipitation in the presence of carbonate ions in solution of a calcium phosphate apatite with a Ca/P molar ratio greater than the stoichiometric value of 1.67 for hydroxyapatite (HA). The resulting calcium-rich carbonate apatite is sintered/heat-treated in a carbon dioxide atmosphere to produce a single-phase, crystalline carbonate-substituted hydroxyapatite. In contrast to previous methods for producing B- or AB-type carbonate-substituted hydroxyapatites, no sodium or ammonium ions, which would be present in the reaction mixture from the sodium or ammonium carbonates commonly used as a source of carbonate ions, were present in the final product. The chemical and phase compositions of the carbonate-substituted hydroxyapatite was characterized by X ray fluorescence and X-ray diffraction, respectively, and the level and nature of the carbonate substitution were studied using C-H-N analysis and Fourier transform infrared spectroscopy, respectively. The carbonate substitution improves the densification of hydroxyapatite and reduces the sintering temperature required to achieve near-full density by approximately 200 degrees C compared to stoichiometric HA. Initial studies have shown that these carbonate substituted hydroxyapatites have improved mechanical and biologic properties compared to stoichiometric hydroxyapatite. PMID- 11774333 TI - Bonelike apatite growth on hydroxyapatite-gelatin sponges from simulated body fluid. AB - In vitro bioactivity of gelatin sponges and hydroxyapatite-enriched gelatin sponges was tested through evaluation of the variations in their composition and morphology after soaking in simulated body fluid (1.5) for periods up to 21 days at 37 degrees C. The presence of hydroxyapatite inside the sponges promotes the deposition of bonelike apatite crystals. The deposits are laid down as spherical aggregates, with mean diameters increasing from about 1-2 microm, after 4 days of soaking in simulated body fluid solution, up to about 3.5 microm in the samples soaked for 21 days. Simultaneously, the relative amount of inorganic phase increases up to about 56% wt, leading to a composite material with a composition quite close to that of bone tissue. The inorganic phase is a poor crystalline carbonated apatite similar to trabecular bone apatite. PMID- 11774334 TI - Solution deposition of hydroxyapatite on titanium pretreated with a sodium ion implantation. AB - Titanium surfaces were treated by exposing them to a beam of sodium ions. Sodium titanate was shown to be incorporated within the oxidic titanium surface. The ion implanted surfaces were examined for their reactivity by immersion in a simulated body fluid, which showed the formation of surface-bound hydroxyapatite. The surface was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and optical and electron microscopy. The surface hydroxyl concentration was determined using the nuclear reaction (1)H((15)N, alpha gamma)(12)C. Surface-related parameters that may affect hydroxyapatite nucleation are discussed in terms of the electrical double layer. PMID- 11774335 TI - Chemical coding and electrophysiology of enteric neurons expressing neurofilament 145 in guinea pig gastrointestinal tract. AB - Electrophysiologic recording and indirect immunofluorescence were combined to study localization of the medium-sized neurofilament 145 (NF145) component of the cytoskeleton in morphologically identified neurons in the myenteric and submucosal plexuses of the guinea pig enteric nervous system. Neuronal localization of chemical markers, including calbindin DK28, calretinin, nitric oxide synthase, choline-acetyltransferase, neuropeptide Y, serotonin, neurokinin 1 receptor protein, and somatostatin, was integrated with electrophysiologic and morphologic results for a more complete assessment. NF145 immunoreactivity (-IR) was present in ganglion cells with Dogiel type I morphology in the myenteric plexus of the stomach and small and large intestine. NF145-IR was not found in myenteric ganglion cells with Dogiel type II morphology. NF145-IR was not present in any of the ganglion cells in the submucosal plexus. NF145 was expressed in nerve fibers in both myenteric and submucosal plexuses. The majority of these fibers were identified as sympathetic postganglionic axons based on their disappearance in organotypic culture and on their expression of tyrosine hydroxylase. The myenteric ganglion cells with NF145-IR had electrophysiologic properties of S-type enteric neurons. NF145-IR was found in neurons with vasoactive intestinal peptide, serotonin, nitric oxide synthase, somatostatin, and neurokinin 1 receptor but not with neuropeptide Y or calbindin. The results in general suggest that NF145 is localized to distinct subsets of myenteric motor neurons and interneurons. Absence of NF145 from ganglion cells in the submucosal plexus is an example of differences between myenteric and submucosal components of the enteric nervous system. PMID- 11774336 TI - Catecholaminergic innervation of the sympathetic preganglionic cell column of the filefish Stephanolepis cirrhifer. AB - Nerve fibers immunoreactive for enzymes synthesizing catecholamines were examined in the central autonomic nucleus, a column of sympathetic preganglionic neurons, in the filefish Stephanolepis cirrhifer. Varicose nerve fibers immunoreactive for tyrosine hydroxylase were densely distributed in the rostral part, sometimes in contact with perikarya but were sparse in the caudal part of this nucleus. Fluorescent double labeling distinguished noradrenergic nerve fibers immunoreactive for both tyrosine hydroxylase and dopamine beta hydroxylase, and dopaminergic fibers immunoreactive only for tyrosine hydroxylase. In the brainstem, catecholaminergic neurons were observed in the locus coeruleus, the caudal dorsomedial reticular zone of the medulla, and the area postrema. Double labeling of tyrosine hydroxylase and dopamine beta hydroxylase showed that the neurons in the locus coeruleus were all noradrenergic, and those in the caudal dorsomedial medulla were mostly noradrenergic, whereas the area postrema contained both noradrenergic and dopaminergic neurons. No catecholaminergic neurons were found in the ventral region of the brainstem. After application of DiI to the central autonomic nucleus, retrogradely labeled neurons were seen in the caudal dorsomedial medulla but not in the locus coeruleus or the area postrema. These findings suggest that the sympathetic preganglionic neurons of the filefish may receive noradrenergic axonal projections from neurons in the caudal dorsomedial medulla. In the light of previous studies, inputs of these catecholaminergic fibers to the central autonomic nucleus may be involved in regulation of sympathetic activity of peripheral organs, together with serotoninergic and peptidergic inputs to this nucleus. PMID- 11774337 TI - Protein kinase C-induced disorganization and endocytosis of photosensitive membrane in Limulus ventral photoreceptors. AB - Protein kinase C (PKC) desensitizes the light response in photoreceptors from the ventral optic nerve of the horseshoe crab Limulus. Photoisomerization of Limulus rhodopsin leads to phosphoinositide hydrolysis, resulting in the production of inositol trisphosphate and diacylglycerol (DAG). Inositol trisphosphate mobilizes intracellular stores of Ca(2+), resulting in photoreceptor excitation in Limulus, while DAG may activate PKC. We investigated whether PKC-mediated desensitization of the photoresponse is accompanied by ultrastructural changes in the rhodopsin bearing photosensitive membrane (rhabdom) in Limulus ventral photoreceptors. PKC activation by (-)-indolactam V in darkness induces disorganization and swelling of the rhodopsin-containing microvilli and endocytosis of rhabdomeral membrane. The effects of (-)-indolactam V on dark-adapted photoreceptor ultrastructure are reversible, are stereospecific, are blocked by coapplication of PKC inhibitors, and closely match those induced by continuous, bright light. Rhabdom disorganization and endocytosis via PKC activation may, therefore, contribute to desensitization of the light-adapted photoreceptor. PMID- 11774338 TI - Neurons labeled from locomotor-related ventrolateral funiculus stimulus sites in the neonatal rat spinal cord. AB - Spinal cord/brainstem preparations from 5- to 8-day-old rats, maintained in vitro, were used to determine the cells of origin and regions of termination of fibers in the superficial ventrolateral funiculus (VLF) at a site from which rhythmic locomotor-like activity can be induced. Rhythmic locomotor-like activity was recorded from lumbar ventral roots after short trains of stimuli (50 Hz for 0.5-2 seconds) delivered to the VLF. Field potential mapping revealed that single VLF stimuli elicited responses in the ipsilateral ventrolateral medulla. Tract tracing experiments by using biocytin, pressure-injected into the VLF, showed that only a small number of brainstem neurons were labeled and these were scattered bilaterally in the ventrolateral and lateral medulla. Dense concentrations of nerve terminals were found in the lateral reticular nucleus ipsilateral to the stimulation site. Labeled spinal cord neurons included a primary population of large cells distributed bilaterally in lamina VII from T13 to L4, with peak numbers in L2 ipsilaterally and in L3 contralaterally. Intracellular recordings revealed that some L2 and L3 neurons with rhythmic responses to VLF stimulation could be activated antidromically from the VLF, with latencies of less than 1.0 msec. These observations led us to speculate that the superficial VLF carries a locomotor-related tract originating bilaterally in lumbar lamina VII and terminating in the ipsilateral medulla, including the lateral reticular nucleus. This pathway may be part of the spinoreticular or spinoreticulotectal pathway that has been described in many species, the function of which has only loosely been ascribed. PMID- 11774339 TI - Neonatal development of projections from the basolateral amygdala to prefrontal, striatal, and thalamic structures in the rat. AB - Recently, an animal model for neurodevelopmental disorders has been developed. In this model, the effects of an early neonatal (postnatal day 7 [Pd 7]) basolateral amygdala lesion are compared with the effects of a lesion later in life (Pd 21). The reported data indicate that amygdala damage at a specific point early in life results in enduring behavioral disturbances that become more manifest after puberty, for example, only an early lesion resulted in a disruption of the prepulse inhibition, which is also observed in people suffering from schizophrenia. Accordingly, it was postulated that the early damage may affect the neuroanatomic and neurochemical organization and functioning of other brain structures. This was studied by use of the anterograde tracers biotinylated dextran amine and Phaseolus vulgaris-leucoagglutinin. At neonatal days 7, 9, 11, 13, and 26, amygdaloid fibers were in particular present in the mediodorsal thalamus (MDT), nucleus accumbens (Acb), and prefrontal cortex (PFC). The development of the topography of the amygdaloid innervation, however, differed markedly for the MDT and Acb compared with the PFC. For the MDT and Acb, no major changes in innervation were observed between Pd 7 and Pd 26, whereas the innervation of the PFC reorganized from a neonatal diffuse (Pd 7 and 9) to a restricted pattern (Pd 11, 13, and 26). In addition, the innervation changed to an adult-like bilaminar pattern. These data provide information on the circuitry that may be involved in the aberrant neurodevelopment of neonatally amygdala lesioned rats, which have been proposed as an animal model for neurodevelopmental psychopathological disorders. PMID- 11774340 TI - Early development of the retina and pineal complex in the sea lamprey: comparative immunocytochemical study. AB - Lampreys have a complex life cycle, with largely differentiated larval and adult periods. Despite the considerable interest of lampreys for understanding vertebrate evolution, knowledge of the early development of their eye and pineal complex is very scarce. Here, the early immunocytochemical organization of the pineal complex and retina of the sea lamprey was studied by use of antibodies against proliferating cell nuclear antigen (PCNA), opsin, serotonin, and gamma aminobutyric acid (GABA). Cell differentiation in the retina, pineal organ, and habenula begins in prolarvae, as shown by the appearance of PCNA-negative cells, whereas differentiation of the parapineal vesicle was delayed until the larval period. In medium-sized to large larvae, PCNA-immunoreactive (-ir) cells were numerous in regions of the lateral retina near the differentiated part of the larval retina (central retina). A late-proliferating region was observed in the right habenula. Opsin immunoreactivity appears in the pineal vesicle of early prolarvae and 3 or 4 days later in the retina. In the parapineal organ, opsin immunoreactivity was observed only in large larvae. In the pineal organ, serotonin immunoreactivity was first observed in late prolarvae in photoreceptive (photoneuroendocrine) cells, whereas only a few of these cells appeared in the parapineal organ of large larvae. No serotonin immunoreactivity was observed in the larval retina. GABA immunoreactivity appeared earlier in the retina than in the pineal complex. No GABA-ir perikaryon was observed in the retina of larval lampreys, although a few GABA-ir centrifugal fibers innervate the inner retina in late prolarvae. First GABA-ir ganglion cells occur in the pineal organ of 15-17 mm larvae, and their number increases during the larval period. The only GABA-ir structures observed in the parapineal ganglion of larvae were afferent fibers, which appeared rather late in development. The time sequence of development in these photoreceptive structures is rather different from that observed in teleosts and other vertebrates. This suggests that the unusual development of the three photoreceptive organs in lampreys reflects specialization for their different functions during the larval and adult periods. PMID- 11774342 TI - Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. AB - In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down. PMID- 11774341 TI - Functional circuitry involved in the regulation of whisker movements. AB - Neuroanatomical tract-tracing methods were used to identify the oligosynaptic circuitry by which the whisker representation of the motor cortex (wMCx) influences the facial motoneurons that control whisking activity (wFMNs). Injections of the retrograde tracer cholera toxin subunit B into physiologically identified wFMNs in the lateral facial nucleus resulted in dense, bilateral labeling throughout the brainstem reticular formation and in the ambiguus nucleus as well as predominantly ipsilateral labeling in the paralemniscal, pedunculopontine tegmental, Kolliker-Fuse, and parabrachial nuclei. In addition, neurons in the following midbrain regions projected to the wFMNs: superior colliculus, red nucleus, periaqueductal gray, mesencephalon, pons, and several nuclei involved in oculomotor behaviors. Injections of the anterograde tracer biotinylated dextran amine into the wMCx revealed direct projections to the brainstem reticular formation as well as multiple brainstem and midbrain structures shown to project to the wFMNs. Regions in which retrograde labeling and anterograde labeling overlap most extensively include the brainstem parvocellular, gigantocellular, intermediate, and medullary (dorsal and ventral) reticular formations; ambiguus nucleus; and midbrain superior colliculus and deep mesencephalic nucleus. Other regions that contain less dense regions of combined anterograde and retrograde labeling include the following nuclei: the interstitial nucleus of medial longitudinal fasciculus, the pontine reticular formation, and the lateral periaqueductal gray. Premotoneurons that receive dense inputs from the wMCx are likely to be important mediators of cortical regulation of whisker movements and may be a key component in a central pattern generator involved in the generation of rhythmic whisking activity. PMID- 11774343 TI - Lack of correlation between AT frequency and genome size in higher plants and the effect of nonrandomness of base sequences on dye binding. AB - BACKGROUND: Different plant species vary as to the ratio of nucleotide base pairs of genomic DNA. A correlation between genome size and base pair ratio has been claimed. Base composition can be analyzed by base-specific dyes. METHODS: Genome size is determined by flow cytometry of suspensions of nuclei stained by the base independent dye, PI. For estimation of the AT frequency, the AT-specific dyes 4,6 diamidino-2-phenylindole, dihydrochloride (DAPI) and Hoechst 33342 (HO) were used. We define a dye factor (DF) as the ratio of the two estimates (peak ratios) of nuclear fluorescence intensities of sample relative to reference plant nuclei using a given dye and an intercalating fluorochrome. RESULTS: No significant correlation between genome size and the DF for DAPI was found when 54 plant species were investigated. However, similarities within and differences among the plant families were shown. The comparison of DAPI and HO DFs gave no consistent differences as would be predicted from the model of different binding site length of dyes. This result may be explained by the nonrandom distribution of base pairs. CONCLUSIONS: There is no general correlation between genome size and AT/GC ratio in higher plants. Similar AT/GC ratios within a plant family result from the general similarity of the DNA sequences within a family. The fluorescence of base-specific dyes is influenced by the nonrandom distribution of bases in the DNA molecule. PMID- 11774345 TI - Karyotyping of comparative genomic hybridization human metaphases by using support vector machines. AB - BACKGROUND: Comparative genomic hybridization (CGH) is a relatively new molecular cytogenetic method for detecting chromosomal imbalance. Karyotyping of human metaphases is an important step to assign each chromosome to one of 23 or 24 classes (22 autosomes and two sex chromosomes). Automatic karyotyping in CGH analysis is needed. However, conventional karyotyping approaches based on DAPI images require complex image enhancement procedures. METHODS: This paper proposes a simple feature extraction method, one that generates density profiles from original true color CGH images and uses normalized profiles as feature vectors without quantization. A classifier is developed by using support vector machine (SVM). It has good generalization ability and needs only limited training samples. RESULTS: Experiment results show that the feature extraction method of using color information in CGH images can improve greatly the classification success rate. The SVM classifier is able to acquire knowledge about human chromosomes from relatively few samples and has good generalization ability. A success rate of moe than 90% has been achieved and the time for training and testing is very short. CONCLUSIONS: The feature extraction method proposed here and the SVM-based classifier offer a promising computerized intelligent system for automatic karyotyping of CGH human chromosomes. PMID- 11774344 TI - Determination of individual cell Michaelis-Menten constants. AB - BACKGROUND: A novel methodology for the measurement and analysis of apparent K(M) (Michaelis-Menten constant) and V(MAX) values of individual cells is suggested. It is based on a mathematical model that considers substrate influx into the cell, its intracellular enzymatic hydrolysis, and the product efflux. The mathematical formulation was approximated linearly in order to analyze intracellular substrate conversion characteristics via Michaelis-Menten theory. METHODS: Utilizing static cytometry, the time dependence of the fluorescence intensity [FI(t)] emitted from prelocalized and defined FDA stained cells was recorded. This required frequent periodical measurements of the same cells, which are sequentially exposed to various fluorogenic substrate concentrations. RESULTS: Model simulations correlated with experimental results. Differences in distributions of individual K(M) and V(MAX) values of cells incubated with and without PHA were evident. Average K(M) and V(MAX) values of PHA-stimulated cells increased by 99% and 540%, respectively. CONCLUSIONS: This study may provide a tool for assessing intracellular enzymatic activity in individual intact cells under defined physiologic conditions. This may open new vistas in various areas, giving answers to critical questions arising in the field of cell and developmental biology, immunology, oncology, and pharmacology. PMID- 11774346 TI - The dynamic process of apoptosis analyzed by flow cytometry using Annexin V/propidium iodide and a modified in situ end labeling technique. AB - BACKGROUND: To study the apoptotic process in time, we used the following flow cytometric (FCM) techniques: phosphatidylserine (PS) translocation by Annexin-V (AnV), DNA fragmentation by in situ end labeling (ISEL), and propidium iodide (PI) staining. Because PS translocation is assumed to be an early feature of programmed cell death (PCD), we questioned if AnV positivity implies inevitable cell death. METHODS: Apoptosis was induced in Jurkat cells by gamma-irradiation, incubation with camptothecin (CPT), or cytosine beta-D-arabinofuranoside (Ara-C). At different time intervals, PCD was quantified by AnV/PI and ISEL. To analyze the influence of cell handling procedures on PCD, we applied these three FCM techniques on CD34+ bone marrow (BM) stem cells after selection and after a freeze-thaw procedure. Various AnV/PI- CD34+ fractions were cultured in a single cell single-well (SCSW) assay. RESULTS: Jurkat cells under three different detrimental conditions showed essentially the same pattern of apoptosis in time. Initially developed AnV+/PI- cells subsequently (within 1 h) showed ISEL positivity, after which they turned into AnV+/PI++ cells with even higher levels of ISEL positivity (80-90%). Eventually, they lost some of their PI and ISEL positivity and formed the AnV+/PI+ fraction. Cell handling of CD34+ cells caused high and variable AnV+/PI- fractions (overall range 23-62%). Within total AnV+ and AnV+/PI- populations, only a minority of CD34+ cells showed ISEL positivity (range 4-8% and 0.8-6%, respectively). Different fractions of AnV+/PI- CD34+ cells did have clonogenic capacity. CONCLUSIONS: PCD of cell suspensions in vitro can be followed accurately in time by these three FCM techniques. PS translocation is followed rapidly (within 1 h) by oligo-nucleosomal DNA fragmentation, after which cell (and nuclear) membrane leakage occurs. Detection of PS asymmetry by AnV-fluorescein isothiocyanate (FITC) is not always associated with (inevitable) apoptosis, as can be concluded from the proliferative capacity of AnV+ /PI- CD34+ cells in the SCSW assay. PMID- 11774347 TI - Sequential immunofluorescence staining and image analysis for detection of large numbers of antigens in individual cell nuclei. AB - BACKGROUND: Visualization of more than one antigen by multicolor immunostaining is often desirable or even necessary to explore spatial and temporal relationships of functional significance. Previously presented staining protocols have been limited to the visualization of three or four antigens. METHODS: Immunofluorescence staining was performed both on slices of formalin-fixed tissue and on cells in culture. Images of the stained material were recorded using digital imaging fluorescence microscopy. The primary and secondary antibodies, as well as the fluorophores, were thereafter removed using a combination of denaturation and elution techniques. After removal of the fluorescence stain, a new immunofluorescence staining was performed, visualizing a new set of antigens. The procedure was repeated up to three times. A method for image registration combined with segmentation, extraction of data, and cell classification was developed for efficient and objective analysis of the image data. RESULTS: The results show that immunofluorescence stains in many cases can be repeatedly removed without major effects on the antigenicity of the sample. CONCLUSIONS: The concentration of at least six different antigens in each cell can thus be measured semiquantitatively using sequential immunofluorescence staining and the described image analysis techniques. The number of antigens that can be visualized in a single sample is considerably increased by the presented protocol. PMID- 11774349 TI - The bioinformatics of microarray gene expression profiling. PMID- 11774350 TI - Aligning experimental design with bioinformatics analysis to meet discovery research objectives. AB - The utility of genomic technology and bioinformatic analytical support to provide new and needed insight into the molecular basis of disease, development, and diversity continues to grow as more research model systems and populations are investigated. Yet deriving results that meet a specific set of research objectives requires aligning or coordinating the design of the experiment, the laboratory techniques, and the data analysis. The following paragraphs describe several important interdependent factors that need to be considered to generate high quality data from the microarray platform. These factors include aligning oligonucleotide probe design with the sample labeling strategy if oligonucleotide probes are employed, recognizing that compromises are inherent in different sample procurement methods, normalizing 2-color microarray raw data, and distinguishing the difference between gene clustering and sample clustering. These factors do not represent an exhaustive list of technical variables in microarray-based research, but this list highlights those variables that span both experimental execution and data analysis. PMID- 11774351 TI - Studying the heterogeneity of brain tumors using medium throughput LOH analysis. PMID- 11774352 TI - Establishing a molecular continuum in breast cancer DNA microarrays and benign breast disease. AB - Although the risk of breast cancer for women in the United States is approximately 1 in 9, identification of risk factors and translation of that knowledge into strategies for prevention have been inhibited by poor understanding of disease pathogenesis. A few benign breast proliferations are associated with higher risks of breast cancer, but definition of a preneoplastic morphologic continuum is lacking. If progression from a premalignant state to malignancy is accompanied by genetic changes, then identification in benign breast disease lesions (BBD) of alterations similar to those found in breast cancer should strengthen the perception of BBD as a premalignant condition. Current testing for hereditary breast cancer susceptibility presumes that only women with invasive breast or ovarian cancer are gene carriers. Therefore, neither in situ breast cancer nor atypical hyperplasias are considered clinically as evidence of a breast-ovarian syndrome, nor are these diagnoses used to predict carrier status within at-risk families. This reflects lack of evidence that breast cancer develops along a recognized morphologic continuum from precursor lesions. New mutation screening procedures such as DNA microarrays can provide sensitivity, specificity, and high throughput that circumvent limitations imposed on the scope of molecular marker analyses applied to archival resources. We have studied a BRCA1-mutant individual with loss of the wild type BRCA1 allele in benign breast proliferations. Both her benign and malignant lesions showed molecularly identical TP53 mutations, indicating that significant genetic alterations can occur in BBD and supporting the clonal evolution from BBD to malignancy. PMID- 11774353 TI - Transcriptional profiling develops molecular signatures for ovarian tumors. AB - Of the cancers unique to women, ovarian cancer has the highest mortality rate. Over 26,000 women are diagnosed with this disease in the U.S. annually, and 60% of those diagnosed will die of the disease. One of the greatest problems with this disease is the lack of strong early warning signs or symptoms resulting in advanced stage at presentation in most women, followed by the outgrowth of chemotherapy-resistant disease in the majority of patients. The 5-year survival for patients with early stage disease ranges from 50-90%, but it is less than 25% for advanced-stage disease. In collaboration with researchers at Millennium Predictive Medicine (Cambridge, MA), the Ovarian Cancer Program of the Mayo Clinic Cancer Center analyzed gene expression in over 50 primary ovarian tumors, as compared with normal ovarian epithelial cells. The technologies utilized included microarray analysis with nitrocellulose filters containing 25,000 arrayed human cDNAs, as well as the construction of subtraction suppression hybridization cDNA libraries and their subsequent sequencing. Our specific focus has been on genes that are underexpressed during the development of ovarian cancer, although this analysis has revealed a large number of consistently up- and down-regulated genes. There were more down-regulated genes in ovarian tumors than up-regulated genes. In addition, the number of genes that had altered expression levels was quite large. For example, we found 409 genes down-regulated at least 5-fold, and 72 genes up-regulated at least 5-fold in 33% of the tumors analyzed. We also observed that most of the expression alterations observed in later stage (Stages III/IV) tumors were also observed in early-stage tumors (Stages I/II). This was corroborated using comparative genomic hybridization analysis on the same tumors that were expression profiled. This analysis revealed that the late-stage tumors had more gene amplification than early-stage tumors, but most regions of change (either increases or decreases) were in common between different stage tumors. We also have verified the altered expression levels of several of these genes using several complementary strategies. Finally, we are taking top candidate genes that are consistently under-expressed in ovarian tumors and attempting to determine their functional role in the development of ovarian cancer. PMID- 11774354 TI - Prospects of admixture linkage disequilibrium mapping in the African-American genome. PMID- 11774355 TI - Using mRNA expression profiling to determine anticancer drug efficacy. AB - Pharmacogenomics is a fast-growing field of investigations that aims to further elucidate the inherited nature of interindividual differences in drug disposition and effects, with the ultimate goal of providing a stronger scientific basis for selecting the optimal drug therapy. Providing the right drug for the right patient is an important problem in the treatment of cancer. This is mainly due to the lack of information about the sensitivity of the tumor for a specific treatment modality, such as either chemotherapy or radiation treatment. This presentation highlights two approaches to identify responsiveness to treatment. Both approaches are based on the identification of expression profiles. The first approach concentrates on drug resistance and the second on the signaling pathways leading up to the death of the cell. Both approaches provide expression profiles; however, the more dynamic expression profiling as used to determine the signaling in damage cells promises to be a better determinant for the pharmacogenomic changes in expression profiles and, consequently, a potential better determinant for drug efficacy. PMID- 11774356 TI - Painting with a molecular brush: genomic/proteomic interfacing to define the drug action profile of novel solid-tumor selective anticancer agents. AB - XK469 is an investigational anticancer agent that exhibits antiproliferative activity in tumor-bearing animal models. We examined the drug-action profile of this agent at the molecular level regarding alterations induced in gene expression and proteins in HCT-116 human colon adenocarcinoma cells. We used a unique cDNA microarray (GeneMap(TM) Cancerarray) comprising 1152 human tumor related genes and 2-D gel electrophoresis, respectively, following a 24-hour exposure to a drug concentration that killed a two-log fraction of HCT-116 clonogenic cells. Functional gene cluster profile (FGCP) analysis of the 71 out of 1152 genes that displayed a >2-fold increase or decrease in expression (over untreated control) identified a drug-specific involvement of the MAPK signal transduction pathway. MAPK signaling together with the involvement of ubiquitin proteins from 2-D gel electrophoresis suggest a novel drug-action profile at the molecular level for the in vitro antiproliferative activity of XK469. PMID- 11774357 TI - Nitric oxide donors induce large-scale deletion mutations in human lymphoblastoid cells: implications for mutations in T-lymphocytes from arthritis patients. AB - Rheumatoid arthritis (RA) is an inflammatory disease in which high levels of reactive nitrogen oxygen species (RNOS) may be present in the affected joints. RNOS are known to produce small-scale mutational events (transitions, transversions, small insertions, and small deletions) but the ability of these compounds to cause deletion of large segments of genomic DNA has not been previously determined. To address this question, a human lymphoblastoid cell line (WIL2-NS) was exposed to nitric oxide (NO)-donating drugs and hypoxanthine phosphoribosyltransferase (hprt)-negative clones were selected and analyzed by multiplex-PCR. Large-scale deletions accounted for 60-80% of hprt mutations arising in drug-treated cultures compared to 12% in untreated cultures (P-values of 0.006 and 0.0001, respectively, in two experiments). Deletion mutations in untreated cultures affected exon 9, whereas 75% of drug-induced deletion mutations affected exons 2, 3, and 9, and the remainder were very large, ranging from 26 to 1200 kbp. To compare this spectrum of NO-induced mutations in a lymphoblastoid line to that arising in vivo in arthritis patients, T-cells from RA patients, osteoarthritis (OA) patients, and controls were cloned and similarly analyzed. We previously showed that the overall frequency of Hprt mutant clones from patients is appreciably elevated compared to that of control subjects. Large scale hprt deletions (0.5 to >26 kb) were detected in mutant T-cell clones from both RA and OA patients and also from control subjects. A total of 54 mutant clones from 16 RA patients and 19 mutant clones from 6 OA patients were studied. Of these, 6 clones (from 3 RA and 1 OA patient) had suffered large-scale deletions. A total of 9 control subjects were studied and 62 mutant clones were obtained. Of these, 19 had suffered large-scale deletions, arising in 7 of 9 control subjects. In conclusion, (1) RNOS are capable of inducing large-scale deletion mutations in a human lymphoblastoid cell line and (2) large-scale deletion mutations were found in 10-30% of T-cell clones from RA and OA patients and controls, which we hypothesize may be induced by RNOS. PMID- 11774358 TI - Extended quantitative structure-activity relationships for 80 aromatic and heterocyclic amines: structural, electronic, and hydropathic factors affecting mutagenic potency. AB - The mutagenic/carcinogenic heterocyclic amines formed during the cooking of protein foods have been determined to be probable or possible human carcinogens. As part of a comprehensive study of the food mutagens, our laboratory has produced a series of quantitative structure-activity relationships (QSARs) of aromatic and heterocyclic amines, to attempt to elucidate the mechanisms of mutagenesis/carcinogenesis. Amines are genotoxically active only after activation by a series of reactions converting the parent compound to an electrophilic derivative, which is postulated to be a nitrenium ion that covalently binds to and damages DNA. An important agent in this conversion is cytochrome P450. In this report we develop a QSAR for 80 amines of diverse structure and a range of 10 orders of magnitude in mutagenic potency. New structural factors and quantum chemical ab initio and Huckel calculations are included. The results are interpreted to show that a main determinant of mutagenic potency is the extent of the aromatic pi-electron system. Small contributions are made by both the dipole moment and the calculated stability of the nitrenium ion. Multiple linear regression models account for nearly two-thirds of the variance in potency, leaving room for additional unknown factors. The role of cytochrome P450 1A in amine toxification is supported, and further theoretical and experimental research on its reaction mechanisms and modeling of its active site are proposed. PMID- 11774359 TI - Point mutations induced by 1,2-epoxy-3-butene N1 deoxyinosine adducts. AB - The National Toxicology Program has recently classified 1,3-butadiene (BD) as a human carcinogen. BD is metabolized to the intermediates 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-dihydroxy-3,4-epoxybutane. All three metabolites have been implicated in producing specific types of DNA damage and as genotoxic agents in mice, rat, and human cells. This study has focused on EB induced N1 deoxyinosine lesions that are formed by deamination of deoxyadenosine following reaction of the epoxide at the N(1) position. The R and S stereoisomers of this lesion were incorporated site-specifically within the context of an 11 mer oligodeoxynucleotide, incorporated into M13mp7L2 single-stranded DNA, and transfected into E. coli. Both stereoisomers modestly reduced plaque-forming ability, indicating that neither lesion presents a base modification that cannot be bypassed. The resulting plaques were assessed for point mutations using differential hybridization and DNA sequence analyses. The overall mutagenic spectrum revealed that the N1 adducts were highly mutagenic (approximately 90% per replication cycle), causing a predominance of A --> G transitions. PMID- 11774360 TI - Comparable DNA and chromosome damage in Chinese hamster ovary cells by chlorohydroxyfuranones. AB - Chlorinated drinking water contains several chlorohydroxyfuranone (CHF) by products whose contribution to cancer risk is not presently known. 3,4-Dichloro-5 hydroxy-2(5H)-furanone (MCA), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), and 3- chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF) were studied for the induction of DNA damage, using the alkaline single-cell gel (SCG)/comet assay, and for chromosome damage, using sister-chromatid exchange (SCE) and chromosome aberration (CA) tests, in Chinese hamster ovary (CHO) cells. 3-Chloro 4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the known genotoxic chlorination by-product and a rat carcinogen, was used as a reference chemical. The SCG analyses were done using concentrations that caused little or no cytotoxicity compared to that of the concurrent control cultures. In the cytogenetic tests, the CHFs were tested up to maximum cytotoxicity. MX and MCA were the most cytotoxic of the compounds in CHO cells followed by CMCF and MCF. All of the CHFs induced DNA damage, SCEs and CAs (mainly chromatid-type breaks and exchanges) in a concentration-related manner, with the exception that MCA was a weak inducer of SCEs. There were no significant differences between the lowest concentration of MX, MCA, and CMCF to cause DNA damage (SCG assay). Based on comparisons of the slopes of regression lines, MX was somewhat more potent than either MCA or CMCF, and MCF was clearly less potent than the other three compounds in the assay. The order of potency was MX > CMCF > MCA > MCF in inducing SCEs and MX > MCA > CMCF > MCF in inducing CAs. The data show that there are differences in the potency of genotoxicity among the CHFs tested. In many cases, however, the extent of maximum effect observed was comparable between the compounds. The results suggest that besides MX other CHFs should be considered in the evaluation of genotoxic risks associated with the consumption of chlorinated drinking water. PMID- 11774361 TI - Modulation of streptonigrin's clastogenic effects in CHO cells by the metal chelating agent 1,10-phenanthroline. AB - The effect of the metal-chelating agent 1,10-phenanthroline (PNT) on the clastogenesis induced by streptonigrin (SN) in CHO cells was investigated. When CHO cells were exposed to SN, chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs) were formed in a dose-dependent manner (P < 0.05). When PNT was present in the culture medium, the production of CAs by SN was strongly inhibited (inhibition range = 54.9-80.8%). Similarly, the induction of SCEs by SN was significantly decreased by the addition of PNT to CHO cultures (P < 0.05), although the effect was minor. This finding suggests that intracellular transition metals are implicated in the clastogenesis by SN, and that the Fenton reaction (Fe(2+) + H2O2 --> OH* + OH(-) + Fe(3+)) may be responsible for the production of CAs by this compound. Moreover, the fact that PNT did not completely inhibit the induction of SCEs by SN suggests that this phenomenon might be attributable to a different mechanism, in which transition metals and free radicals play a minor role. PMID- 11774362 TI - Assessment of DNA damage in lymphocytes of workers exposed to X-radiation using the micronucleus test and the comet assay. AB - The mutagenic and carcinogenic effects of genotoxic agents on exposed people have constituted an increasing concern. Therefore, the objective of this work was to assess DNA damage in lymphocytes of workers exposed to X-radiation using the cytokinesis-blocked micronucleus test and the comet assay (single-cell gel electrophoresis), and to compare these two techniques in the monitoring of exposed populations. The cytokinesis-blocked micronucleus test and the comet assay were employed in the monitoring of 22 workers occupationally exposed to X radiation in a hospital in southern Brazil. The frequency of dicentric bridges was also measured. The results of both assays and the frequency of dicentric bridges revealed a significant increase in genetic effects on the cells of exposed individuals. Age was significantly correlated with micronucleus frequency and damage index in the comet assay. The concomitant analysis of dicentric bridges when determining micronucleus frequency does not require much extra work, and may serve as a reference to the type of mutagenic effect (clastogenic or aneugenic). The combination of the alkaline comet assay with the cytokinesis blocked micronucleus test appears to be very informative for the monitoring of populations chronically exposed to genotoxic agents. PMID- 11774363 TI - Genotoxicity of some sulfur dyes on tadpoles (Rana hexadactyla) measured using the comet assay. AB - This report presents the results of a genotoxicity study to evaluate the DNA damage caused by four sulfur dyes used in the textile and tannery industries. Alkaline single-cell gel electrophoresis assay (SCGE) was performed on erythrocytes from Rana hexadactyla tadpoles following whole-body exposure to increasing concentrations of the dyes. The dyes, along with their active ingredients, were Sandopel Basic Black BHLN, Negrosine, Dermapel Black FNI, and Turquoise Blue. The dye-treated tadpoles showed significant DNA damage, measured as mean DNA length:width ratio, when compared with unexposed control animals. Among the four tested dyes Sandopel Basic Black BHLN appears to be highly genotoxic, Dermapel Black FNI was least genotoxic, and Negrosine and Turquoise Blue were moderately toxic to R. hexadactyla tadpoles. The tadpoles showed a significant reduction in DNA damage when placed in dechlorinated tap water after exposure for a 24-hr period to the dye solutions. PMID- 11774364 TI - Comparison of the mutagenic responses of mismatch repair-proficient (TK6) and mismatch repair-deficient (MT1) human lymphoblast cells to the food-borne carcinogen PhIP. AB - Heterocyclic amines are ubiquitously present in cooked meats and fish. They represent an important class of food-borne carcinogens. We describe the cytotoxic, apoptotic, and mutagenic responses of mismatch repair-proficient (TK6) and mismatch repair-deficient (MT1) human lymphoblastoid cells to PhIP, the most abundant heterocyclic amine. Dose-dependent increases in cytotoxicity, in apoptosis, and in mutant fractions at the hprt locus were observed following PhIP treatment. We present a statistical method that is useful for comparing two populations. With this method, we show that the data fitted a model that assumes that the PhIP-induced mutation rate is dependent on the cell line. Estimated rates of increase of 22.8 x 10(-6) and 2.2 x 10(-6) mutation per cell per microg PhIP were found in MT1 and TK6, respectively, showing that MT1 is hypermutable to PhIP. MT1 also exhibited lower PhIP-induced apoptosis. We conclude from these results that mismatch repair-deficient cells are hypermutable to the food-borne carcinogen PhIP and that the PhIP-DNA adducts, when not eliminated by apoptosis, can be transformed into mutations. PMID- 11774365 TI - Construction of Salmonella typhimurium YG7108 strains, each coexpressing a form of human cytochrome P450 with NADPH-cytochrome P450 reductase. AB - A series of Salmonella typhimurium (S. typhimurium) YG7108 strains, each coexpressing a form of human cytochrome P450 (CYP) (CYP1A1, CYP1A2, CYP1B1, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, or CYP3A5) together with human NADPH cytochrome P450 reductase (OR), was established. The parental S. typhimurium YG7108, derived from TA1535, lacks two O(6)-methylguanine-DNA methyltransferase genes, ada and ogt, and is highly sensitive to the mutagenicity of alkylating agents. The expression levels of CYP holo-protein in the genetically engineered S. typhimurium YG7108 cells, determined by carbon monoxide (CO) difference spectra, ranged from 62 nmol/L culture for CYP2C19 to 169 nmol/L culture for CYP3A4. The expression level of the OR varied, depending on the form of CYP coexpressed, and ranged from 214 to 1029 units/L culture. Each form of CYP expressed in the S. typhimurium YG7108 cells catalyzed the oxidation of a representative substrate at an efficient rate. The rates appeared comparable to the reported activities of CYP expressed in human liver microsomes or CYP in other heterologous systems, indicating that the OR was sufficiently expressed to support the catalytic activity of CYP. These S. typhimurium strains may be useful not only for predicting the metabolic activation of promutagens catalyzed by human CYP but also for identifying the CYP form involved. PMID- 11774366 TI - Predicting the mutagenicity of tobacco-related N-nitrosamines in humans using 11 strains of Salmonella typhimurium YG7108, each coexpressing a form of human cytochrome P450 along with NADPH-cytochrome P450 reductase. AB - Tobacco, including snuff and chewing tobacco, contains N-nitrosamines such as 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NABS), and N nitrosoanatabine (NATB). The role of human cytochrome P450 (CYP) in the metabolic activation of these tobacco-related N-nitrosamines was examined by a Salmonella mutation test using genetically engineered Salmonella typhimurium (S. typhimurium) YG7108 cells each expressing a form of human CYP (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, or CYP3A5) together with human NADPH-cytochrome P450 reductase. Mutagen production from NNK was catalyzed by CYP in the following order: CYP1A2, CYP1A1, CYP1B1, CYP2A6, CYP2C19, CYP3A4. The metabolic activation of one of the N-alkylnitrosamines, NDEA, was mediated by CYP2A6, followed by CYP2E1. Cyclic N-nitrosamines such as NPYR, NPIP, and NMOR were also primarily activated by CYP2A6, and to a lesser extent by CYP2E1. NNN, a pyridine derivative of NPYR, was activated by CYP1A1 at an efficiency similar to that of CYP2A6. NABS, a pyridine derivative of NPIP, was mainly activated by CYP3A4, followed by CYP1A1 and CYP2A6. Thus, the addition of a pyridine ring to NPYR or NPIP altered the forms of CYP primarily responsible for mutagenic activation. NATB was metabolically activated solely by CYP2A6, whereas the genotoxicity of NATB was much lower than that of NNN or NPYR. Based on these data, we conclude that CYP2A6 was responsible for the mutagenic activation of essentially all tobacco-related N-nitrosamines tested in the present study. PMID- 11774367 TI - Genotoxicity of iron chelators in L5178Y mouse lymphoma cells. AB - To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without the addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na2EDTA, phytic acid, and ferrozine. PMID- 11774368 TI - Efficient nonmutagenic replication bypass of DNAs containing beta-adducts of styrene oxide at adenine N(6). PMID- 11774369 TI - Keratins: unraveling the coordinated construction of scaffolds in spermatogenic cells. AB - Recent work shows that two groups of keratins are expressed during mammalian spermatogenesis. One group, belonging to the classic epidermis-type keratins, is present in spermatogonia, spermatocytes, and spermatids. A member of this group, Sak57, a keratin 5 homologue, has been shown to co-align with microtubules and provide a scaffolding shell while also strengthening intercellular cytoplasmic bridges conjoining members of spermatogonial and spermatocyte cohorts. The other, keratin 9, is a component of the perinuclear ring of the manchette, a microtubular structure developed during the elongation and condensation of the spermatid nucleus. The second group, the outer dense fiber (Odf) proteins, is expressed preferentially during mammalian spermiogenesis. The family of Odf proteins-Odf1, Odf2, and Odf3-includes an expanding group of proteins co assembled along the axoneme during the development of the sperm tail. Investigations on the assembly of epidermis-type and Odf sperm tail-targeted keratins are now focused on a group of chaperone-like Odf-binding molecules, designated Spags. Spags appear to drive Odfs to a precise destination. A daunting task is to determine how members of the family of keratins get the signal to produce linear scaffolds in specific spermatogenic cell populations and transport keratins to microtubule-containing structures such as the manchette and axoneme. PMID- 11774370 TI - Expression pattern of HSP25 in mouse preimplantation embryo: heat shock responses during oocyte maturation. AB - Heat shock proteins (HSPs) are known to play an important role not only in various stress conditions such as exposure to heat shock, but also in normal development and/or differentiation. The role of small heat shock proteins such as HSP25 in early embryo development remains largely unknown. In the present study, we examined temporal and spatial expression patterns of HSP25 during mouse preimplantation embryo development. Reverse transcription-polymerase chain reaction (RT-PCR) showed that hsp25 mRNA was detected in unfertilized eggs. Hsp25 mRNA was induced by zygotic gene activation at 2-cell stage, decreased slightly at 4-cell, and re-increased at morula, with the highest level at blastocyst stage. Interestingly, another form of hsp25 variant of which 156 bp (52 a.a.) was truncated within the exon1 region was observed in all stages of preimplantation embryos. We also investigated the sub-cellular localization of HSP25 by fluorescence immunocytochemistry. HSP25 was detected in the cytoplasm under normal developmental condition. While acute heat shock (at 43 degrees C for 30 min) caused no significant changes in the sub-cellular localization of HSP25 in the developing mouse embryos, chronic heat shock (at 43 degrees C for 3 hr) resulted in a denser immunostaining of HSP25 in the nucleus than in the cytoplasm, indicating a nuclear translocation of HSP25 by heat shock. As hsp25 mRNA was detected in the unfertilized egg as a maternal transcript, we examined the expression of hsp25 mRNA with RT-PCR during oocyte maturation under normal and heat shock conditions. Hsp25 mRNA was detected at GV (germinal vesicle)-, GVBD (germinal vesicle breakdown)-, and MII (metaphase II)-oocytes. The expression of hsp25 mRNA was increased markedly by both acute (for 30 min and 1 hr) and chronic (for 4 hr) heat shock, but returned to the basal level during recovery from heat shock in a time-dependent manner, suggesting a thermo protective role of HSP25. In contrast to preimplantation embryos, HSP25 was detected both in the cytoplasm and the nucleus except for the nucleolus, and the cellular localization was not altered by heat shock. Finally, we investigated the effect of heat shock on oocyte maturation. When GV-oocytes were exposed to acute heat shock (at 43 degrees C for 15 min to 1 hr), they underwent the GVBD and the PB (polar body) emission successfully. However, under more stringent heat shock conditions (at 43 degrees C for 2-4 hr), most oocytes were arrested at the GV stage, and the first PB was not developed, indicating that chronic heat shock might be inhibitory to the mouse oocyte maturation. Taken together, these findings suggest that HSP25 is important for mouse preimplantation embryo development and oocyte maturation. PMID- 11774371 TI - Mouse Xist expression begins at zygotic genome activation and is timed by a zygotic clock. AB - The imprinted mouse Xist (X-inactive specific transcript) gene is involved in the initiation of X-chromosome inactivation. Only the paternal Xist is expressed in preimplantation development beginning from the 4-cell stage, preceding and in correlation with paternal X-inactivation in the extraembryonic lineage of the blastocyst. To better understand the mechanisms regulating Xist expression in early development, we investigated the precise timing of its onset. We set up a single-cell RT-PCR for the simultaneous analysis on single embryos of Xist and Hprt (internal control) cDNAs and a Y-chromosome specific DNA sequence, Zfy (for embryo sexing). Applying this procedure, we demonstrate that Xist expression begins at the G2-phase of 2-cell female embryos, earlier than previously reported and at the same time of the major wave of zygotic genome activation (ZGA). We then examined, if Xist expression at the 2-cell stage is dependent on the lapse of time spent since fertilization, as previously reported for zygotic genes. One cell embryos at the G2-phase of the first cell-cycle were cultured with cytochalasin D (inhibitor of cytokinesis but not of DNA synthesis or nuclear progression) for a time equivalent to the 4-cell stage in control, untreated embryos. We show that Xist activation occurs at a scheduled time following fertilization despite the embryos being blocked at the 1-cell stage, suggesting the existence of a zygotic clock involved in the regulation of the transcription of this imprinted gene. PMID- 11774372 TI - Molecular cloning and partial characterization of medaka fish stromelysin-3 and its restricted expression in the oocytes of small growing follicles of the ovary. AB - A cDNA clone (2755-bp) for stromelysin-3 was isolated by screening the cDNA library and by 3'- and 5'-rapid amplification of cDNA ends using ovary RNA of the medaka fish Oryzias latipes. The clone encodes a protein of 492 amino acids. Stromelysin-3 mRNA was detected only in the ovary. In situ hybridization analysis revealed that stromelysin-3 mRNA was localized in the oocyte cytoplasm of small growing follicles. RT-PCR analysis of total RNAs isolated from various-sized follicles and ovulated oocytes was conducted in order to determine the mRNA levels during oocyte growth. The stromelysin-3 mRNA level was the highest in the small follicles, and the mRNA levels decreased as the follicles grew. No significant stromelysin-3 mRNA was detected in the ovulated oocytes or immature ovaries. The fish stromelysin-3 cDNA was expressed in COS-1 cells in order to characterize the intracellular localization of the protein. A 56 kDa protein was synthesized and secreted into the culture medium. The secreted stromelysin-3 exhibited gelatin-degrading activity. PMID- 11774373 TI - Expression of spermadhesin genes in porcine male and female reproductive tracts. AB - Spermadhesins, secretory proteins of the male genital tract, constitute the bulk of seminal plasma proteins in pig. The nucleotide sequences of spermadhesins AWN, AQN-1, and AQN-3 from the cDNAs, derived from seminal vesicles, were determined. The coding sequences of spermadhesins revealed an overall sequence similarity of 40% at nucleotide level. Expression of spermadhesins (AWN, AQN-1, AQN-3, PSP-I, and PSP-II) in porcine male and female reproductive tracts were studied by means of RT-PCR and immunological approaches. All spermadhesins are transcribed and translated in seminal vesicles and prostate. In caudal epididymis mRNA transcripts of all spermadhesins have been detected by RT-PCR. PSP-I showed additional signals in caput epididymis and rete testis. Translation can be detected only for AWN in tissue extracts by SDS-PAGE and Western blotting. Remarkably, AWN is the only spermadhesin that is also expressed in the uterus, the uterotubal junction, and the oviduct of the female genital tract as shown by RT-PCR, cDNA-sequencing, and immunological analysis. In sows at estrus and interestrus, in gilts and gilts 12 hr after insemination no obvious differences were noticed in the pattern of AWN-immunoreactivity in epithelial cells either of the uterotubal junction, isthmus, or ampulla. While strong staining was observed in the superficial uterine glands and in the glands of the uterotubal junction during estrus, in diestrus this declined distinctly. The role of spermadhesins in relation to their expression is discussed. PMID- 11774374 TI - Real-time imaging of beta-lactoglobulin-targeted luciferase activity in the mammary glands of transgenic mice. AB - This study was aimed at establishing a new platform for real-time monitoring of milk-protein gene expression in the mammary glands. A transgenic reporter composed of the beta-lactoglobulin (BLG)/luciferase hybrid gene was targeted to the mammary glands of pregnant and lactating mice and luciferase activity was imaged in vivo with a low-light imaging system. The mammary glands of a 17-day pregnant mouse occupied an area comparable to that of a 6-day lactating mouse. Nevertheless, the intensity of the luciferase signal was much weaker and confined to regions in the inguinal and thoracic glands. A few small and defined locations of higher expression were also detected, indicating diversity in the initiation of this transgenic milk protein expression. In the lactating mice, high inter- and intra-heterogeneity among regions in a particular gland and among glands was demonstrated, and confirmed by ex vivo analysis of luciferase activity in mammary biopsies. The lack of correlation between luciferase activities and levels of beta-casein accumulation in these biopsies resulted, most probably, from the longer half-life of the native milk protein, compared to the activity of the transgenic marker in the tissue. Unilateral sealing of mammary glands for 4 hr resulted in complete abrogation of luciferase activity, establishing the BLG/luciferase transgene as a reliable tool to follow short-term stimuli. Dispersed mammary epithelial cells preserved luciferase activity in culture, and thus could be used for following mammary gland development after re-implantation. The bioluminescence-based methodology presented here eliminates averaging of heterogeneity in gene expression among glands, and misinterpretations resulting from sampling biopsies taken from inactive regions. Imaging luciferase expression in the mammary glands may enable an accurate monitoring of milk-protein gene expression during cyclic periods of development and apoptosis in a limited number of animals, and could be applied for reporting the consequences of selected drugs on milk-protein gene expression. PMID- 11774375 TI - Direct injection of foreign DNA into mouse testis as a possible in vivo gene transfer system via epididymal spermatozoa. AB - We have attempted to transfect testicular spermatozoa with plasmid DNA by direct injection into testes to obtain transgenic animals [this technique was thus termed "testis-mediated gene transfer (TMGT)"]. When injected males were mated with superovulated females 2 and 3 days after injection, (i) high efficiencies (more than 50%) of gene transmission were achieved in the mid-gestational F0 fetuses, (ii) the copy number of plasmid DNA in the fetuses was estimated to be less than 1 copy per diploid cell, and (iii) overt gene expression was not found in these fetuses. These findings suggest the possibility that plasmid DNA introduced into a testis is rapidly transported to the epididymis and then incorporated by epididymal spermatozoa. The purpose of this study was to elucidate the mechanism of TMGT by introducing trypan blue (TB) or Hoechst 33342 directly into testis. We found that TB is transported to the ducts of the caput epididymis via rete testis within 1 min after testis injection, and TB reached the corpus and cauda epididymis within 2-4 days after injection. Staining of spermatozoa isolated from any portion of epididymis was observed 4 days after injection of a solution containing Hoechst 33342. Injection of enhanced green fluorescent protein (EGFP) expression vector/liposome complex into testis resulted in transfection of epithelial cells of epididymal ducts facing the lumen, although the transfection efficiency appeared to be low. In vivo electroporation toward the caput epididymis immediately after injection of EGFP expression vector into a testis greatly improved the uptake of foreign DNA by the epididymal epithelial cells. PCR analysis using spermatozoa isolated from corpus and cauda epididymis 4 days after injection of a DNA/liposome complex into testis revealed exogenous DNA in these spermatozoa even after treatment with DNase I. These findings indicate that exogenous DNA introduced into tesits is rapidly transported to epididymal ducts via the rete testis and efferent ducts, and then incorporated by epithelial cells of epididymis and epididymal spermatozoa. PMID- 11774376 TI - Accumulation of cytoplasmic lipid droplets in bovine embryos and cryotolerance of embryos developed in different culture systems using serum-free or serum containing media. AB - In this study, the quantitative fluctuation of cytoplasmic lipid droplets (LD) and cryotolerance were investigated in bovine embryos derived from in vitro matured (IVM) and in vitro-fertilized (IVF) oocytes developed in different culture systems using serum-free or serum-containing media. The serum-free cultures were grown using IVMD101 medium in conjunction with bovine cumulus/granulosa cell (BCGC) cocultures or IVD101 medium without BCGC cocultures, and the serum-containing cultures were grown in the presence of BCGC cocultures using HPM199 medium supplemented with 5% calf serum (HPM199 + CS). Large numbers of sudanophilic LD were present in the cytoplasm of bovine embryos from 2-cell to hatched blastocyst stages, and the number and size differed between the embryos cultured in serum-free and serum-supplemented media. In the embryos cultured in HPM199 + CS, large (2-6 microm in diameter) sudanophilic LD increased significantly from the morula to the blastocyst stages. Throughout the embryonic development, the embryos developed in serum-free cultures with and without BCGC cocultures had numerous sudanophilic LD, but most of these droplets were small (<2 microm in diameter) and large LD were less numerous than those embryos cultured in HPM199 + CS. Giant LD (>6 microm in diameter) were frequently observed in morulae and blastocysts (including early blastocysts) developed in HPM199 + CS. Electron microscopic observations demonstrated that large LD were abundant in the cytoplasm of trophoblast and embryonic (inner cell mass) cells of blastocysts cultured in HPM199 + CS. These large LD were identified as osmophilic LD, an indication that these lipid inclusions contained a significant proportion of unsaturated lipids. Many elongated mitochondria were found in embryos developed in IVMD101 and IVD101 at the morula and early blastocyst stages, whereas many of the mitochondria in the morulae developed in HPM199 + CS were of an immature form such as spherical or ovoid shape. The survival and hatching rates of embryos (morulae, early blastocysts, and blastocysts) produced in serum free media (both IVMD101 and IVD101) after post-thaw culture were superior to those of embryos produced in serum-containing medium. These results showed that bovine embryos cultured in serum-containing medium abnormally accumulated cytoplasmic lipids into their cytoplasm and the excess accumulation of cytoplasmic LD in embryos may affect the cryotolerance of embryos. PMID- 11774377 TI - Apoptosis in the preimplantation mouse embryo: effect of strain difference and in vitro culture. AB - Cell death by apoptosis occurs predominantly in the inner cell mass (ICM) of the blastocyst, the cell population which carries the germ line and gives rise to the foetus. The frequency of apoptosis in blastocysts varies widely within outbred species such as human and cow. We have addressed the basis of this variation by examining the relative influence of strain difference and in vitro culture conditions on apoptosis, using embryos from two different strains of mice (MF1 and C57BL6/CBA) in two different culture media (M16 and kSOM). In both strains and all crosses apoptosis was first detected by nuclear fragmentation or TUNEL [Terminal deoxynucleotidyl transferase mediated d-UTP nick end-labelling] labelling at the early blastocyst stage. This was true for embryos which had developed in vivo, and in vitro in both M16 and kSOM. The apoptotic index in blastocysts was found to be significantly different between both media and strain (P < 0.0001). Blastocysts from MF1 x MF1 at equivalent stages had an apoptotic index of 32.4% in M16 and 20.3% in kSOM. Blastocysts from C57BL6/CBA x C57BL6/CBA had an apoptotic index of 19.3% in M16 and 14.4% in kSOM. When embryos of similar cell number were compared, a significantly greater apoptotic index was found for cultured MF1 x MF1 embryos with a cell number between 40 and 59 compared to similar directly flushed C57BL6/CBA embryos (P = 0.001), and MF1 embryos (P < 0.0005). MF1 x MF1 embryos and C57BL6/CBA x MF1 embryos of 60-79 cells had a greater apoptotic index in M16 than kSOM (P < 0.0005) but the difference between media was not significant for C57BL6/CBA x C57BL6/CBA. When strain was compared MF1 x MF1 embryos of 60-79 cells had a significantly greater apoptotic index than C57BL6/CBA x MF1 in both media (P < 0.0005 M16; P = 0.002 kSOM) and than C57BL6/CBA x C57BL6/CBA in M16 (P = 0.019). Our data suggest that genetic make-up and the chemical composition of simple medium are equally important in determining the level of apoptosis. PMID- 11774378 TI - Ultrastructural studies on developing follicles of the spotted ray Torpedo marmorata. AB - Light and ultrastructural investigations on sub-adult and adult sexually mature females, demonstrates that in Torpedo marmorata folliculogenesis starts in the early embryo and that the two ovaries in the adult contain developing follicles of various sizes and morphology. Initially, the follicle is constituted by a small oocyte, surrounded by a single layer of squamous follicle cells. The organization is completed by a basal lamina and, more externally, by a theca, that at this stage is composed by a network of collagen fibers. As the oocyte growth goes on, during previtellogenesis and vitellogenesis, the organization of the basal lamina and of the oocyte nucleus does not change significantly. The basal lamina, in fact, remains acellular and constituted by fibrils intermingled in an amorphous matrix; the nucleus always shows an extended network of chromatin due to the lampbrush chromosomes, and one or two large nucleoli. By contrast, the granulosa (or follicular epithelium), the ooplasm, and the theca cells significantly change. The granulosa shows the most relevant modifications becoming multi-layered and polymorphic for the progressive appearance of intermediate and pyriform-like cells, located respectively next to the vitelline envelope, or spanning the whole granulosa. The appearance of intermediate cells follows that of intercellular bridges between small follicle cells and the oocyte so that one can postulate that, as in other vertebrates, small cells differentiate into intermediate, and then pyriform-like cells, once they have fused their plasma membrane with that of the oocyte. Regarding the ooplasm, one can observe as in previtellogenic follicles, it is characterized by the presence of intermediate vacuoles containing glycogen, while in vitellogenic follicles by an increasing number of yolk globules. The theca also undergoes significant changes: initially, it is constituted by a network of collagen fibers, but later, an outermost theca esterna containing cuboidal cells and an interna, with flattened cells, can be recognized. The role of the different constituents of the ovarian follicle in the oocyte growth is discussed. PMID- 11774379 TI - Flow cytometric sperm sorting: effects of varying laser power on embryo development in swine. AB - This study was conducted to determine fertilization rate and embryo development using the Beltsville Sperm Sexing Technology with two different laser power outputs, 25 and 125 milliwatts (mW). Freshly ejaculated boar semen was diluted; one aliquot was not stained or sorted (nonsort) and a second aliquot was stained with Hoechst 33342 and sorted as a complete population, not separated into X and Y populations (all-sort). Ovulation controlled gilts were surgically inseminated with 2 x 10(5) spermatozoa (44-46 hr after human chorionic gonadotropin (hCG)) into the isthmus of each oviduct, one oviduct receiving nonsort and the other all sort at 25 or 125 mW. A total of 426 embryos were flushed from oviducts at slaughter 43 hr after laparotomy and prepared for determination of fertilization and cleavage rates using confocal laser microscopy for analysis of actin cytoskeleton and chromatin configuration. The percentage of fertilized eggs and embryos was less for the 25 mW all-sort compared to nonsort or the 125 mW all sort (77.9 vs. 96.3 and 96.2%, P < 0.05). The percentage of fragmented embryos was greater for the 25 mW all-sort than the nonsort (15.2 vs. 4.5%, P < 0.05), but did not differ significantly from 125 mW all-sort mean (7.2%). The percentage of normal embryos (80.4% overall) did not differ (P > 0.05) among treatments. However, the rate of embryo development was slower (P < 0.05) after insemination with the 25 mW all-sort spermatozoa compared to nonsort spermatozoa. Embryos in the 3-4 and 5-9 cell stages for the 25-mW all-sort and nonsort were 78 and 20% vs. 49 and 50%, respectively. The embryo percentages for the 125 mW (3-4 and 5-9 cell stages, 59 and 35%) did not differ significantly (P > 0.05) from the nonsort or 25 mW all-sort. We conclude that the use of 125 mW laser power for sorting boar spermatozoa is advantageous to maintain high resolution separation and has no detrimental effect on embryo development compared to 25 mW. PMID- 11774380 TI - Cyclooxygenase-2 is expressed by cumulus cells during oocyte maturation in cattle. AB - Prostaglandins could be involved in various aspects of final differentiation of ovarian follicles. Prostaglandins are generated by the cyclooxygenase (cox) pathway. Until now, the expression pattern of isoforms cox-1 and cox-2 of cyclooxygenase in bovine cumulus-oocyte complexes (COCs) was unknown. Using immunodetection procedure, we demonstrated in the present study that cox-2 was expressed by cumulus cells during in vivo and in vitro maturation. Time course induction of cox-2 expression was investigated during in vitro maturation using Western blot analysis. Specific signal of cox-2 was markedly evidenced from 6 hr of culture and increased to reach a maximal level at 24 hr of culture. In vitro, cox-2 expression in COCs was associated with increased concentrations of PGE(2) and PGF(2alpha) in the maturation medium. In addition, the effects of culture conditions on cox-2 expression was considered using RT-PCR and Western-blot analysis. We demonstrated that the addition of 10 ng/ml of EGF to TCM199 clearly increased the expression level of cox-2 mRNA and protein. Higher levels of in vitro cox-2 expression was associated with greater rates of cumulus expansion and oocytes at metaphase II at 24 hr of culture. In conclusion, our present results suggest that cox-2 expression in cumulus cells may be involved in differentiation of COCs that occurs during oocyte maturation. PMID- 11774381 TI - Molecular cloning of Odf3 encoding a novel coiled-coil protein of sperm tail outer dense fibers. AB - The outer dense fibers (ODF) are the main cytoskeletal structures of the sperm tail found in animals with internal fecundation. They consist of at least 14 polypeptides from which only a few are identified due to difficulties in isolation of the protein components. Here we report the isolation and molecular characterization of Odf3, encoding a novel protein of rat sperm ODF. Odf3 is transcribed in testes and more specifically in spermatids but it is also expressed in epididymides and brain suggesting a possible involvement in building of the cellular cytoskeleton. Odf3 encodes a putative protein of approximately 110 kDa. Secondary structure predictions indicated that ODF3 is a coiled-coil protein. The identification of coiled-coil proteins as constituents of outer dense fibers reveals a model for ODF formation. PMID- 11774382 TI - Sperm-zona pellucida interaction involves a carbonyl reductase activity in the hamster. AB - For successful fertilization to occur, the spermatozoa must transit through an egg-specific extracellular matrix or zona pellucida (zp) to reach and ultimately fuse with the oocyte plasma membrane. This process involves ligand-receptor recognition between the zp and the acrosomal cap of the sperm. The hamster sperm protein P26h, a receptor which is acquired during epididymal transit, has been suggested to act in sperm-zp binding. The cloning and characterization of the full-length cDNA-encoding hamster P26h revealed 85% identity with a porcine lung carbonyl reductase. To better understand the mechanism by which P26h interacts with zp proteins, we investigated carbonyl reductase activity during gamete interactions. In the present study, we show that specific inhibitors of carbonyl reductase such as diclofenac and phenylbutazone decreases sperm-zp binding without affecting the motility, progressivity or acrosome integrity of sperm. We also detected, and partly purified, carbonyl reductase activities from cauda epididymal sperm protein extract and this activity was associated with an enriched fraction of P26h. Removing P26h from the partly purified protein fractions by immunoaffinity chromatography led to the loss of carbonyl reductase activity. The findings that sperm-zp binding is blocked by carbonyl reductase inhibitors and that P26h is active in mature sperm suggest that P26h could play an important role in the fertilization process. PMID- 11774383 TI - Parthenogenetic activation and subsequent development of rat oocytes in vitro. AB - Studies were undertaken to determine whether electrical stimulation, or ethanol treatment alone or in combination with 6-dimethylaminopurine (6-DMAP) influenced the rate of parthenogenetic activation of rat oocytes. The percentages of activated oocytes with pronuclei (89-91%) and those developed to the two-cell stage (68-72%) were significantly higher after electrical stimulation with direct current (DC) at 100 V/mm, 99 microsec once or twice, than when other DC voltages (75, 150, and 200) were applied or when ethanol or 6-DMAP treatment was given alone. However, none of the activated oocytes developed beyond the four-cell stage. The percentages of activated oocytes with pronuclei (100%) that developed to the two-cell (100%), eight-cell (89%) and blastocyst stages (50%) were significantly higher when electrical stimulation was followed by treatment with 2 mM 6-DMAP for 4 hr than when other combined procedures were applied. In conclusion, the results of the present study clearly showed that combined treatment of electrical stimulation or ethanol with 6-DMAP induces parthenogenetic activation and subsequent development of rat oocytes in vitro. PMID- 11774384 TI - Characterization and potential function of a novel testis-specific nucleoporin BS 63. AB - A 1933 bp cDNA fragment, coding a truncated testis-specific novel nucleoporin, was isolated from a human testis lambdaZAPII cDNA library, designated as BS-63 and assigned GenBank accession number: U64675. By applying the methods of rapid amplification of cDNA ends (5' RACE) and PCR, a full-length BS-63 cDNA composed of 5475 bp was obtained. BS-63 cDNA contained an open reading frame consisting of 1765 codons and XFXFG or GLFG repetitive sequence motifs. These repetitive motifs are structural characteristic of nucleoporins. BS-63 cDNA has high homology with Nup358/Ran BP2. A 1599 bp fragment, corresponding to the C-terminus of BS-63 cDNA, was prepared and expressed in E. coli BL21(DE3). The recombinant product was purified by affinity chromatography and SDS-PAGE and polyclonal antibodies raised. In rat testis section, the BS-63 protein was localized at the sites of nuclear pores in spermatids by immuno-gold transmission electron microscopy and on the nuclear membrane of Triton X-treated sperm by colloidal silver immuno-gold scanning electron microscopy. The recombinant BS-63 protein can be phosphorylated in vitro with PKC and p34(cdc2). A yeast two-hybrid system was used to screen a mouse testis cDNA library to identify proteins capable of interacting with BS-63. Using the 1.6 kb cDNA fragment as bait, the following interacting proteins were identified: Ran, transportin (karyopherin beta2), two proteins related to the nucleocytoplasmic transporter and aF10 protein. The latter protein is a putative transcriptor containing a cysteine-rich N-terminus, a LAP/PHD finger, a leucine zipper domain and a glutamine-rich C-terminus. Also it is highly expressed in murine testis and is located in the cell nucleus and cytoplasm. The interaction of BS-63 with aF10 (696-1001aa) was validated by surface plasmon resonance and by affinity precipitation combined with Western blot. aF10 (696-1001aa) interacted in vitro with BS-63 extracted from rat testis germ cells. It is hypothesized that BS-63 is a testis-specific nucleoporin and possibly acts as a docking site and a cotransporter of Ran and transportin. The complex performs the task of a carrier system in transporting aF10 into the nucleus of germ cells during spermiogenesis. PMID- 11774386 TI - Preoperative assessment for and outcomes of mandibular conservation surgery. AB - INTRODUCTION: The role of marginal mandibulectomy and other conservative resective procedures for patients with early cortical mandibular invasion from squamous carcinoma of the oral cavity remains poorly defined. The purpose of this retrospective study was to evaluate the efficacy of preoperative assessment for bone invasion and the outcomes of different mandibular resective procedures that preserve mandibular continuity. METHODS: The charts of 222 patients treated at the University of Texas M. D. Anderson Cancer Center between 1960 and 1990 were reviewed. All patients had a biopsy-confirmed diagnosis of squamous carcinoma involving either the lower gingiva, floor of mouth, oral tongue, or retromolar trigone. All patients had a surgical resection that involved removing less than a segment of the mandible. Patient data were analyzed to determine the usefulness of preoperative assessment and outcomes of therapy. RESULTS: Clinical evaluation of mandibular bone invasion was more sensitive than radiologic evaluation, whereas radiologic assessment was more specific and had a higher reliability index. The overall local and regional recurrence and distant metastasis rates for all T stages were 14.4%, 18.0%, and 2.7%, respectively. Sixty-nine point eight percent of all patients were without evidence of disease 2 years after treatment. CONCLUSIONS: Mandibular conservation surgery is oncologically safe for patients with early mandibular invasion. Accurate preoperative assessment that combines clinical examination and radiographic evaluation is better than either modality alone, but clinical judgment is still necessary for proper patient selection. PMID- 11774387 TI - Quantitative analysis from CT is prognostic for local control of supraglottic carcinoma. AB - BACKGROUND: The purpose of this study was to determine whether pretreatment imaging with CT was prognostic for control of the primary site in patients with squamous cell carcinoma of the supraglottic larynx. METHODS: Pretreatment CT studies were obtained on 28 patients treated definitively with radiation therapy for supraglottic larynx cancer between 1991 and 1997. Follow-up ranged from 20-58 months. RESULTS: Local control was achieved in 61% of patients. Tumor volumes ranged from 0-68.6 cm(3), with a median of 3.1 cm(3). Local control rates for tumors with volumes greater than or less than 8 cm(3) were 20% and 70%, respectively (p =.0077). Mean tumor volumes for patients with and without recurrences were 10 cm(3) and 3.4 cm(3), respectively. CONCLUSIONS: This study demonstrates that quantitative analysis from CT imaging is prognostic for control of the primary site when radiation therapy is given for treatment of supraglottic cancer. PMID- 11774388 TI - Neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands. AB - INTRODUCTION: Pleomorphic adenoma is the most common neoplasm arising in the salivary glands. Surgical management is the primary therapeutic modality. With the use of modern surgical techniques, recurrence is infrequent, and facial nerve sparing is the norm. However, for patients with recurrent disease, the risk of further relapses is increased with surgical resection alone, particularly for those patients in whom multiple recurrences have already occurred. The role of adjuvant radiotherapy in this setting remains uncertain. Although neutron radiotherapy is superior to conventional radiotherapy for malignant salivary gland tumors, its role in the treatment of pleomorphic adenomas is less well defined. We report our experience using this modality for high-risk, recurrent pleomorphic adenomas. METHODS: Sixteen patients were treated with neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands from 1986 through 1993. The median age at diagnosis was 33 years (range, 11-77 years); median age at the time of neutron radiotherapy was 52 years (range, 22-77 years); median number of prior surgical procedures was 3 (range, 1-6); median duration from initial diagnosis to radiotherapy was 14.5 years (range, 3 months-30 years); median follow-up was 83 months (range, 9-144 months). The median period at risk for survivors was 96 months (defined as the interval from completion of neutron radiotherapy to last follow-up). Ten patients had evidence of gross residual disease at the time of treatment as determined by imaging studies, with nine patients having multinodular disease. RESULTS: The 10-year actuarial survival was 79%. One patient died from lung metastases 9 months after treatment; one patient died from a liver tumor of uncertain origin, but the histology could not rule out a metastasis from the previous pleomorphic adenoma; and one patient died from recurrent disease at the base of skull. The 15-year actuarial locoregional control rate was 85%. One of the two patients with locoregional recurrence had a malignant transformation into an adenocarcinoma. No statistical difference in 15 year actuarial survival (75% vs 83%, p =.82) was found comparing patients with gross residual disease vs microscopic residual disease. The actuarial 15-year locoregional control was 76% for patients with gross residual disease vs 100% for those with microscopic disease. The 15-year actuarial risk of RTOG/ESTRO nonaudiologic grade III/IV complications was 21%. No facial nerve injuries were observed as a direct consequence of neutron radiotherapy. CONCLUSIONS: Neutron radiotherapy offers both excellent local control rates and survival rates in patients with multiply recurrent pleomorphic adenomas that are not candidates for surgical resection, even in the presence of gross residual disease. The treatment related morbidity is acceptable. Malignant transformations and metastases, although uncommon, may be observed in this tumor. PMID- 11774389 TI - Management of swallowing in supraglottic and extended supraglottic laryngectomy patients. AB - BACKGROUND: Aspiration of food and liquid following supraglottic and supracricoid laryngectomy has been documented and found to be the most frequent major postoperative complication that extends hospitalization. The advantages as well as disadvantages of discharging a patient with percutaneous endoscopic gastrostomy (PEG) placement and home therapy versus an aggressive in-hospital dysphagia management program remain controversial. The present investigation examines an aggressive in-patient postoperative dysphagia management program following decannulation. METHODS: Twenty-one patients participated in a four-part dysphagia management program following decannulation: patient education, indirect therapy, swallowing evaluation, and nutrition education. RESULTS: Eleven patients achieved functional swallowing goals prior to discharge with no reports of pneumonia or rehospitalization over a 3-month follow-up period. Six patients were discharged with a tracheostomy and duo tube; five of these patients were started on an oral diet the same day of decannulation. Four patients decannulated prior to discharge did not achieve functional swallowing. CONCLUSION: Certain patients can achieve functional swallowing goals prior to discharge and avoid the cost and surgical placement of a PEG. This group required an additional 2 to 3 days of hospitalization; however, the usual and customary charges for aggressive dysphagia management in this group were exceeded by charges for PEG placement and in-home therapy according to pricing guidelines for the hospital where these patients were treated. Specific patient profiles of those who were unsuccessful relate to extent of surgery, ie, supraglottic + base of tongue (SUPRA + BOT) and supraglottic + vocal fold (SUPRA + VF) resection, and non-compliance. Complicated patients often require longer rehabilitation and may benefit from a PEG at the time of surgery. PMID- 11774390 TI - Non-steroidal anti-inflammatory drugs inhibit telomerase activity in head and neck squamous carcinoma cell lines. AB - BACKGROUND: Antiproliferative effects in neoplastic cells of different origin have been attributed to non-steroidal anti-inflammatory Drugs (NSAIDs) during the past few decades. METHODS: We tested the influence of NSAIDs and hydrocortisone on cell lines derived from head and neck squamous cell cancer (HNSCC) and on normal oral mucosal keratinocytes. Cell numbers were assayed by cell counting, proliferation, telomerase activity with a colorimetric assay, and cell cycle distribution by flow cytometry. RESULTS: In the neoplastic cell lines indomethacin and ibuprofen caused a dose-dependent reduction of cell numbers and telomerase activity without altering cell viability and increased the percentage of cells in G0/G1 phase. In normal oral mucosal keratinocytes, only minor effects could be detected in response to NSAIDs and hydrocortisone. CONCLUSION: These results demonstrate that NSAIDs have activity against HNSCC cells in vitro and may have clinical applications in combination with other therapeutic regimens. PMID- 11774391 TI - Positron emission tomography in the evaluation of stage III and IV head and neck cancer. AB - BACKGROUND: Detection of metastatic disease in head and neck cancer patients is critical to preoperative planning, because patients with distant metastasis will not benefit from surgical therapy. Conventional radiographic modalities, such as CT and MR, give excellent anatomic detail but poorly identify unenlarged lymph nodes harboring metastatic disease. OBJECTIVE: A pilot study was conducted to evaluate the usefulness of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) detection of metastatic disease in patients with advanced-stage head and neck cancer. METHODS: Total body FDG-PET imaging was performed in a prospective manner on 12 consecutive patients with a new diagnosis of stage III or IV mucosal squamous cell carcinoma of the head and neck. Chest CT was also performed on all 12 patients. Patients found to have metastatic disease on either CT or PET imaging underwent procedures to obtain histopathologic confirmation of disease. RESULTS: Three patients (25%) had FDG-PET scans demonstrating metastatic disease. Two of these patients had no evidence of disease on chest radiograph or chest CT but were noted to have positive FDG-PET imaging within the mediastinal lymphatics. Mediastinoscopy was performed confirming metastatic disease in these patients. The third patient had a peripheral lung lesion detected on chest radiograph, CT, and FDG-PET. This nodule was diagnosed by CT-guided biopsy as squamous cell carcinoma. CONCLUSION: FDG-PET scanning detected mediastinal disease in two patients (17%) with advanced-stage head and neck squamous cell carcinoma that was not identified with conventional imaging techniques. PET imaging seems to have significant potential in the detection of occult metastatic disease, particularly in the mediastinal lymphatics. PMID- 11774392 TI - Vocal process granuloma. AB - BACKGROUND: This review article reports the evolution of knowledge regarding the benign proliferations of the posterior glottis commonly termed "vocal process granuloma". METHODS: A comprehensive review of publications addressing lesions of the posterior glottis is affected to analyze the contemporary management of vocal process granuloma. RESULTS: Contemporary management emphasizes interventions to decrease irritation to the posterior glottis. Multiple causes of this irritation preclude use of a single management plan that will successfully address all cases. CONCLUSIONS: Management to diminish laryngopharyngeal reflux, as well as to correct vocally abusive behavior, will appropriately address the majority of vocal process granuloma. Surgical removal is best reserved for cases when conservative management fails, when airway obstruction is a concern, or when a biopsy is needed to establish the diagnosis. Ancillary measures that may be beneficial in specific cases include the use of steroids, antibiotics, membranous vocal fold augmentation, and laryngeal botulinum neurotoxin injection. PMID- 11774393 TI - Malignant triton tumor of the nasal cavity. AB - BACKGROUND: Malignant triton tumor is usually an aggressive sarcoma consisting of a malignant schwannoma with rhabdomyoblastic differentiation. However, malignant triton tumor of the nasal cavity is very rare. METHODS: A case report of a 38 year-old woman with polypoid mass, which bled easily in the right nasal cavity, and nasal obstruction is presented with a review of the literature pertaining to this unusual case. RESULTS: The malignant triton tumor was treated with wide surgical excision followed by radiation therapy. Histopathological diagnosis of the malignant triton tumor was made on the surgical specimen. The patient's postoperative course was unremarkable, and follow-up at 5 years reveals no evidence of disease. CONCLUSIONS: A malignant triton tumor in the nasal cavity is a rare disease. Head and neck surgeons should recognize the possibility of malignant triton tumor occurring in the nasal cavity. PMID- 11774394 TI - MALT lymphoma of the salivary gland. PMID- 11774395 TI - Cancer metastasis to a percutaneous gastrostomy site. PMID- 11774396 TI - Preoperative evaluation of patients with parathyroid adenoma: role of high resolution ultrasonography. AB - BACKGROUND: Unilateral parathyroid exploration with adenoma removal and identification of a normal parathyroid gland is a controversial surgical approach to the treatment of primary hyperparathyroidism. The aim of this study was to evaluate the ability of high-resolution ultrasonography to localize adenomas preoperatively and to assess the effect of such localization on operative time. METHODS: One hundred twenty consecutive previously non-operated patients with primary hyperparathyroidism underwent ultrasonography before surgery, which consisted of unilateral neck exploration. The procedure was changed to bilateral exploration when justified by the surgical findings. RESULTS: The sensitivity and positive predictive value of the ultrasonographic examinations were 89% and 98%, respectively. These results were obtained regardless of the size of the adenoma. No significant difference was found in the presence of thyroid multinodular disease (p =.2). A positive sonographic examination decreased the operative time to an average of 59 minutes. The average size of the adenomas was 19 mm (range, 4 55 mm). A positive and highly statistically significant correlation was found between adenoma size and both preoperative calcium level (p =.01) and parathyroid hormone level (p =.0001). CONCLUSIONS: In experienced hands, high-resolution ultrasonography can be a cost-effective means of localizing parathyroid adenomas when unilateral neck exploration is considered the acceptable surgical approach. PMID- 11774397 TI - A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy. AB - BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge. PMID- 11774398 TI - Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis. AB - BACKGROUND: The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma. METHODS: We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs. RESULTS: There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p =.04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p =.02) and in the group of SCCs (p =.01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p =.1) and was significantly associated with increased vascularization (p =.03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p =.02) and increased tumor vascularization correlated with higher cGMP levels (rs =.4; p =.01). CONCLUSIONS: Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC. PMID- 11774399 TI - Differential expression of c-jun and c-fos mRNAs in squamous cell carcinoma of the head and neck: associations with uPA, gelatinase B, and matrilysin mRNAs. AB - BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are known for their invasive behavior. The invasiveness of these tumors requires proteases, some of which as urokinase-type plasminogen activator (uPA), gelatinase B and matrilysin are regulated through AP-1 dependent transcriptional mechanisms. AP-1 consists of several proteins, including those encoded by the proto-oncogenes c-jun and c-fos. The aim of this study was to: first, evaluate the expression levels of matrix metalloproteases (matrilysin and gelatinase B) and uPA mRNAs; second, examine whether these genes might be associated with c-jun and c-fos expression; third, examine the relationship between the expression of these genes and HNSCC clinico pathological features. METHODS: We have analyzed 38 HNSCC primary tumors and matched mucosa tissues for uPA, gelatinase B, matrilysin, c-fos, and c-jun by Northern-blot analysis. RESULTS: uPA, gelatinase B, matrilysin, and c-jun mean levels were statistically higher in the tumors than in the normal adjacent mucosa, whereas no difference was found when c-fos mRNA values were compared, c jun mRNA expression correlated directly with gelatinase B and matrilysin mRNA levels, but no association with uPA mRNA was observed, c-fos mRNA levels were not associated with the tested proteases, but low levels were determined in tumors from older patients who subsequently developed a 2(nd) tumor. No evidence of correlation between expression of uPA, matrilysin, and c-jun in tumors and clinico-pathological features was found. Gelatinase B mRNA high levels were associated to presence of cervical recurrences. CONCLUSION: Expression of c-jun seems to be involved in the regulation of gelatinase B and matrilysin being not related to uPA. Lack of association with c-fos may indicate that other fos family members might play a role in the transcriptional activity of the analyzed proteases in HNSCC tumors. PMID- 11774400 TI - Transforming growth factor beta1 and beta2 (TGFbeta2 / TGFbeta2) profile changes in previously irradiated free flap beds. AB - BACKGROUND: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes and the expression of cytokines involved in wound healing could be observed. These processes lead to a delayed healing of free flaps in the graft bed. The aim of the present experimental study was to analyze the expression profiles of transforming growth factor (activated TGFbeta(1), TGFbeta(2)) and latency associated peptide (LAP) in the irradiated graft beds and the transition area between grafts and irradiated graft beds. METHODS: In Wistar rats (male, weight 300-500 g) undergoing preoperative irradiation of the neck region with 30 Gy (30 animals) and non-irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The interval between irradiation and transplantation was 4 weeks. In each group on postoperative days 3, 7, 14, and 28, cytoplasmatic expression of activated TGFbeta(1), LAP, and TGFbeta(2) was analyzed by immunohistochemistry to determine labeling indices (positive stained cells/total cells). RESULTS: The success rate in graft beds irradiated with 30 Gy was 76% and in non-irradiated graft beds was 86% (p =.02). In the graft beds irradiated with 30 Gy, there was an increased expression of activated TGFbeta(1) (range, 19.0-33.0), LAP (14.0-21.0), and TGFbeta(2) (3.0-19.5) together with obvious fibrosis. The expression was located in perivascular fibroblasts and endothelial cells. In contrast, a lower expression of activated TGFbeta(1) (11.0-21.0), LAP (1.0-8.0), and TGFbeta(2) (0.0-0.9) (p =.006) was observed in non-irradiated graft beds. In the transition area between graft and irradiated graft bed, high expression of activated TGFbeta(1) (37.0), LAP (19.0), and TGFbeta(2) (16.7-33.4) was observed on the 3rd postoperative day in contrast to the transition area in non-irradiated graft beds (activated TGFbeta(1) 26.0, LAP 7.0, and TGFbeta(2) 0.l). CONCLUSION: The radiation induced, increased de novo synthesis of LAP, activation of TGFbeta(1), and increased expression of TGFbeta(2) may represent at least one mechanism for the increased fibrosis and wound healing disorders seen in irradiated tissues and in the transition area to graft tissue. The expression of TGFbeta(1,) LAP, and TGFbeta(2) might possess prognostic value with regard to wound healing and fibrosis in previously irradiated graft beds. PMID- 11774401 TI - Vascularization in the transition area between free grafted soft tissues and pre irradiated graft bed tissues following preoperative radiotherapy in the head and neck region. AB - BACKGROUND: The healing of free vascular grafts in a pre-irradiated graft bed is characterized by an increased risk of wound healing disorders. For that reason, the aim of this study was to examine quantitative vascularization pattern between free vascular grafts and the pre-irradiated graft bed as a function of the preoperative irradiation dose. METHODS: A total of 217 free microvascular hard and soft tissue grafts were used within 199 patients in the head and neck region to cover defects after ablative tumor surgery. Seventy-six patients (group 1) had no prior radiation (RT), 50 patients (group 2) were treated with preoperative radiochemotherapy using 40 to 50 Gy and 5-FU/cisplatin, and 73 patients (group 3) had prior RT (60-70 Gy) between 1 and 7 years before surgery. After healing of the grafts, samples were taken from 42 patients from the graft, the irradiated graft bed, and the transition area between graft and irradiated graft bed. Samples were analyzed as follows: capillary sprouting, structural changes, and distribution patterns were analyzed by immunohistochemical staining (CD34 labeling of capillary endothelium). Three histological sections (2-4 microm) per sample were examined histomorphometrically (ratio capillary area/total area, capillary lumen, and the number of capillaries) by (National Institute of Health) NIH-image-digitized measurements. A statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney test (two-tailed p <.05). RESULTS: The success rate of vascular grafts in group 1 (0 Gy) was 94%, in group 2 (40-50 Gy/5 FU/cisplatin) 90%, in group 3 (60-70 Gy) 84%. In contrast to groups 1 and 2, group 3 showed qualitatively reduced and more irregular capillary distribution with more marked pericapillary fibrosis in the irradiated tissue. Quantitatively, the ratio capillary area/total area, as a marker of improved capillarization, was significantly reduced in group 3 (median 0.01; IQR 0.02) compared with group 1 (median 0.53; IQR 0.32) and group 2 (median 0.44; IQR 1.40) (p <.001). CONCLUSION: After preoperative RT, vascularization of the graft bed decreased continuously as a function of the total dose and time after RT. The results strongly advocate the use of a primary reconstruction after a time interval between 4 and 6 weeks following preoperative RT and suggest the use of a total radiation dose of 40 to 50 Gy. PMID- 11774402 TI - Melan-A as a useful diagnostic immunohistochemical stain for the diagnosis of primary sinonasal melanomas. AB - BACKGROUND: Sinonasal melanomas are rare neoplasms whose diagnosis may require confirmatory immunohistochemical stains. S-100 protein and HMB-45, the stains most commonly used, have varying sensitivities and specificities. Melan-A, a more recent melanoma-specific marker, may prove helpful when S-100 protein and HMB-45 stains are negative or equivocal. METHODS: Seven cases of sinonasal melanoma were assessed for reactivity with Melan-A, S-100 protein and HMB-45. RESULTS: The study group consisted of two women and five men ages 40 to 83. Six of the neoplasms were strongly positive for S-100 protein. One case was negative for S 100 protein and HMB-45 but positive for Melan-A. HMB-45 staining varied between diffusely positive (three cases), focally positive (two cases), and negative (two cases). All cases were positive for Melan-A either diffusely (four cases) or focally (three cases). CONCLUSION: Because Melan-A can be positive in cases that are S-100 protein or HMB-45 negative, it is a useful component in the immunohistochemical panel for the diagnosis of sinonasal melanomas. PMID- 11774403 TI - Hypercalcemia associated with parathyroid hormone-related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region. AB - BACKGROUND: Parathyroid hormone-related protein (PTHrP) is mainly responsible for hypercalcemia in squamous cell carcinomas (SCCs). METHODS: We retrospectively checked the appearance of hypercalcemia among 33 patients who died with head and neck SCC. Serum concentrations of C-terminal region of PTHrP (C-PTHrP) were measured in 15 of them. The intracellular PTHrP expression was immunohistochemically stained in 42 SCC sections obtained from the 33 before the appearance of hypercalcemia. RESULTS: Hypercalcemia appeared in 24 of the 33, and increased serum C-PTHrP levels were confirmed in 11 of 12 hypercalcemic patients. PTHrP was identified in all SCC sections, and a stronger intensity than in normal squamous epithelia was observed in 50% of those obtained within 1 year before the onset of hypercalcemia. CONCLUSION: A high incidence of PTHrP-induced hypercalcemia was shown among patients dying with head and neck SCCs. The intracellular increase in PTHrP might be observed preceding hypercalcemia. PMID- 11774404 TI - The predictive value of perioperative calcium levels after thyroid/parathyroid surgery. AB - BACKGROUND: This work was done to determine whether the slope of change between preoperative and early postoperative (2 hr and 8 hr) ionized calcium levels (ciCa) could predict significant postoperative hypocalcemia. METHODS: We did a retrospective chart review of 79 patients undergoing thyroid (n = 56) or parathyroid surgery (n = 23) where overall parathyroid function was felt to be at risk. Results/Conclusions A positive slope between the preoperative ciCa and any postoperative ciCa or the first two postoperative ciCa's predicted normocalcemia in 100% of patients. For the thyroid group, the difference in the slope of the change from preoperative ciCa to first (<2 hours) postoperative ciCa ( 15.940%/hours vs -9.375%/hours, p =.082) did not differentiate patients who developed hypocalcemia (n = 11) and those who remained normocalcemic (n = 45). By contrast the slope of change from preoperative ciCa to the second postoperative (8 hr) ciCa (-1.671%/ hour vs -0.849%/hours, p =.006) and first to second postoperative ciCa (-1.022%/hour vs -0.473%/hour, p =.001) did. For the parathyroid group, none of the differences in similar comparisons between the normocalcemic (n = 20) and hypocalcemic patients (n = 3) approached statistical significance. The relatively small number of patients who became hypocalcemic in this study precluded definition of an absolute slope of calcium level change above which normocalcemia can be assured. PMID- 11774405 TI - Swallowing and speech ability after treatment for head and neck cancer with targeted intraarterial versus intravenous chemoradiation. AB - OBJECTIVE: RADPLAT (concurrent selective supradose intraarterial cisplatin and external-beam irradiation) delivers extraordinarily high cisplatin concentration to head and neck structures. This study was designed to quantify and compare RADPLAT and systemic chemoradiation treatment effects on swallowing and speech. METHODS: Videofluorographic swallowing studies and articulation testing of 14 head and neck cancer patients treated with RADPLAT were compared with 16 treated with systemic chemoradiation 1 month after treatment. RESULTS: RADPLAT and systemic chemoradiation patients did not differ significantly on most swallow outcome measures, and there was significantly less aspiration on 1 and 3 mL liquid for RADPLAT individuals. Speech function was comparable except for RADPLAT's significantly worse /s, z/ productions. CONCLUSIONS: Increased concentration of cisplatin to the head and neck did not result in generally reduced swallowing or articulatory function. PMID- 11774406 TI - Carcinoma of the skin of the head and neck with perineural invasion. AB - BACKGROUND: Perineural invasion is observed in a small subset of patients with carcinomas of the skin of the head and neck. METHODS: Review of the patient literature highlighting the University of Florida experience. RESULTS: Patients with early perineural invasion are asymptomatic, and the phenomenon is discovered only on pathologic examination of the excised lesion. These patients are defined as having "incidental" perineural invasion, and treatment with surgery followed by postoperative irradiation results in a cure rate of approximately 80%. Undiagnosed, the perineural carcinoma slowly progresses and eventually results in symptoms, usually facial weakness or numbness. The disease eventually extends to the skull base and becomes incompletely resectable. Symptomatic patients are defined as having "clinical" perineural invasion, and aggressive treatment results in a cure rate of approximately 45%. CONCLUSIONS: Perineural invasion is an uncommon spread pattern observed in patients with skin cancer and is associated with a relatively poor prognosis. The likelihood of cure is inversely related to the proximal extent of the cancer and is lower for symptomatic compared with asymptomatic patients. PMID- 11774408 TI - Squamous cell carcinoma arising in the skin of a deltopectoral flap 27 years after pharyngeal reconstruction. AB - BACKGROUND: Development of a second primary squamous cell carcinoma in the skin of a flap used for pharyngeal reconstruction is rare. METHODS: A case of squamous cell carcinoma is presented arising in a deltopectoral flap used to reconstruct the hypopharynx 27 years after total laryngectomy. Three previous reports found on review of the literature are summarized. RESULTS: A second primary squamous cell carcinoma may arise in the skin of a myocutaneous flap in the absence of any obvious risk factors. CONCLUSION: We suspect that long-term exposure of the skin of the flap lining the pharynx to saliva may have been a significant factor in the development of this malignancy. Long-term follow up and awareness of this complication is required for patients with soft tissue reconstruction of the oral cavity and pharynx. PMID- 11774407 TI - Anaerobic thyroid abscess from a thyroid cyst after fine-needle aspiration. AB - BACKGROUND: Anaerobic abscess formation within a thyroid cyst is rare but still possible, although aerobic thyroid abscess formation in the thyroid gland after fine-needle aspiration (FNA) has been observed in immunocompromised patients. METHODS: This study describes the clinical manifestations, thyroid echography, cytologic finding, culture outcome, and treatment course of an anaerobic abscess formation within a thyroid cyst after FNA in a healthy subject. RESULTS: A 53 year-old male subject had rapid enlargement of a left thyroid cyst develop after second FNA. Frank pus was obtained through third FNA. The culture outcome was Propionibacterium acnes, which was rich in saliva and one of the pathogens causing periodontitis and gingivitis. After adequate antimicrobial therapy, the abscess gradually diminished. CONCLUSIONS: This article reported, for the first time, on the formation of an anaerobic thyroid abscess after FNA in a healthy subject. We recommended careful aseptic procedure and adequate isolation processes, such as wearing a mask to avoid an unfavorable outcome as a result of a bacterial infection. PMID- 11774409 TI - Malignant melanoma in the palate of a 3-month-old child. AB - BACKGROUND: Malignant mucosal melanoma of the head and neck is a rare cancer in adults that carries a grave prognosis. Three mucosal melanomas in pediatric patients have previously been reported. METHODS: We present here the youngest case of malignant mucosal melanoma of the head and neck in a 3-month-old boy. He presented with a 2 x 2-mm-pigmented lesion on the anterior maxillary alveolus. The patient was treated with local excision alone. RESULTS: The patient has remained disease free with regular follow-up for 117 months. CONCLUSION: Based upon this case and the few cases reported in the literature, mucosal melanoma is a much less common disease in children than in adults. Further, juvenile mucosal melanoma displays a benign clinical behavior. PMID- 11774410 TI - Relapsing paraganglioma of the inferior laryngeal paraganglion: case report and review of the literature. AB - BACKGROUND: Laryngeal paragangliomas are very rare neoplasms derived from the superior or inferior laryngeal paraganglia. The paragangliomas of the inferior laryngeal paraganglion, depending on their anatomic variability, can give rise to two different clinical expressions of the same process, namely the so-called thyroid paragangliomas and the inferior laryngeal or subglottic paragangliomas. METHODS: We present a case for which we have not found any previous descriptions of a cervical and subglottictracheal relapse of a thyroid paraganglioma removed 3 years earlier. We review the literature. RESULTS: We have found a total of 22 paragangliomas of the inferior laryngeal paraganglia, 23 including our case. CONCLUSIONS: Thyroid paragangliomas and inferior laryngeal or subglottic paragangliomas should be included under the term "paragangliomas" of the inferior laryngeal paraganglion. These tumors are slow growing, benign, hypervascular, and much more common in middle-aged women. Immunohistochemistry is essential for its diagnosis. Open, conservative surgery is the treatment of choice. PMID- 11774411 TI - [Influence of interleukin-1 and dexamethasone on prostaglandin production of condylar chondrocytes]. AB - OBJECTIVE: To study the effect of recombinant human interleukin-1(rhIL-1) and dexamethasone on the amount of 6-keto-prostaglandin F1 alpha produced by condylar chondrocytes. METHODS: The concentration of 6-keto-prostaglandin F1 alpha of the chondrocytes supernate was detected respectively at 4, 8, 12, 24, and 72 hours, using the method of radioimmunoassay, after being stimulated by rhIL-1 and dexamethasone for four hours. RESULTS: In normal control group, the concentration of 6-keto-prostaglandin F1 alpha was 1,516.49 ng/L, 1,513.22 ng/L, 1,506.76 ng/L, 1,526.79 ng/L and 2,114.36 ng/L at 4, 8, 12, 24 and 72 hours respectively. In rhIL-1 group, the concentration of 6-keto-prostaglandin F1 alpha was 1,664.32 ng/L at four hours, which was sharply higher than that of the control group(P < 0.01); the concentration of 6-keto-prostaglandin F1 alpha was 1,146.11 ng/L, 949.24 ng/L, 1,392.33 ng/L and 1,481.98 ng/L at 8, 12, 24 and 72 hours respectively, which were sharply lower than that of the control group(P < 0.01). After the condylar chondrocytes were stimulated with dexamethasone for 4 hours, the concentration of 6-keto-prostaglandin F1 alpha decreased more markedly than that of the control group(P < 0.01) throughout the observation period, both in the presence and absence of rhIL-1. CONCLUSION: rhIL-1 could enhance the production of 6-keto-prostaglandin F1 alpha synthesized by condylar chondrocytes. Dexamethasone could inhibit the activity of rhL-1 and the production of 6-keto prostaglandin F1 alpha synthesized by condylar chondrocytes. PMID- 11774412 TI - [The correlation between P-glycoprotein and multidrug resistance of squamous carcinoma in oral and maxillofacial region]. AB - OBJECTIVE: To study the mechanism of drug resistance of oral carcinoma to chemotherapy. METHODS: 40 cases of squamous carcinoma in the oral and maxillofacial region were examined for the multidrug resistance gene product P glycoprotein using a monoclonal antibody MRK16. RESULTS: P-glycoprotein was detected in 62.5% of the sample. P-glycoprotein expression was related to the chemotherapy and the degree of differentiation. P-glycoprotein expression was higher in post-chemotherapy group than in unchemotherapy group (P < 0.05). Well differentiated tumors expressed P-glycoprotein more frequently (P < 0.05). P glycoprotein expression was compared with clinic response to chemotherapy. The accuracy rate of prediction is 75%. CONCLUSION: P-glycoprotein plays an important role in mechanism of multidrug resistance of squamous carcinoma in the oral and maxillofacial region. PMID- 11774413 TI - [Quantitative studies of taste and fungiform papillae on the anterior human tongue]. AB - OBJECTIVE: To study qantitatively in the taste and fungiform papillae on the anterior human tongue. METHODS: Sixty normal adults were evaluated the spatial taste and the fungiform papilla density at spatially-matched sides on the right and left sides of the anterior tongue. The taste stimulative solutions were delivered to a spatially-matched flow chamber attached to the surface of the right or left anterior tongue. RESULTS: (1) There is no statistical difference in number of the fungiform papillae, taste threshold and magnitude matching between right/left, male/female and races; (2) There is a significant difference in fungiform papilla density and taste functions in different individuals; (3) The fungiform papilla density is the key to taste function on 2/3 anterior of tongue, and is positively correlated to it; (4) The use of a spatially-matched flow chamber is a valid test system for overall, objective and accurate evaluating taste on the 2/3 anterior of tongue, and can be used to study quantitatively the fungiform papilla density. CONCLUSION: It is of clinical significance for the diagnosis of taste diseases and the dynamic studies of the taste and the fungiform papillae after lingual nerve injury and repair. PMID- 11774414 TI - [Existence of IL-8 degrading protease and anti-IL-8 IgG in gingival crevicular fluid]. AB - OBJECTIVE: To identify the nature of the IL-8 inhibitor(s) in gingival crevicul fluid (GCF). METHODS: (1) 14 GCF samples were collected from 13 adult periodontitis (AP) patients, and 9 samples were taken from 8 healthy subjects. Each GCF sample was divided into two aliquots. A serine protease-specific inhibitor-PMSF was added to one aliquot and PBS added to the other aliquot as control. ELISA was used to measure IL-8 level in the samples. (2) 41 GCF samples were collected from 15 AP patients and indirect ELISA was performed to detect the anti-IL-8 IgG antibody. RESULTS: (1) IL-8 level in the PMSF-added samples were significantly greater than that in the control group(3.01 mg/L +/- 5.79 mg/L vs 0.05 mg/L +/- 0.15 mg/L, P < 0.001). (2) The mean value of anti-IL-8 IgG in GCF was greater than that of negative control +3 x s. CONCLUSION: A serine protease which can "cleave" IL-8 exists in GCF and GCF from AP sites contain auto-antibody against IL-8. PMID- 11774415 TI - [Inhibition effects of tumor infiltrating lymphocytes from oral cancer on nude mice transplanted tumor established with human tongue carcinoma cell lines]. AB - OBJECTIVE: To observe the in vivo inhibition effects on nude mice transplanted tumor with tumor infiltrating lymphocytes (TILs) isolated from primary mass of oral cancer. METHODS: Established the transplanted tumor model of human tongue cancer at the back of BALB/C nude mice with subcutaneous injection of squamous cell carcinoma lines Tca 8113. TILs isolated from patients with Oral cancer, combining with low dose of cyclophosphamide (Cy: 50 mg/kg), were locally injected into the peripheral site of tumor. The inhibition rate (IR) was calculated by the volume of tumor mass from the 1st to the 8th week, and the weights at the 8th week after tumor dissection. RESULTS: 1. Group TIL + rIL-2 and group TIL + rIL-2 + Cy both exerted a strong inhibition effect on the transplanted tumor within three weeks. The Inhibition rate (IR) were 86.1% +/- 0.4% and 97.7% +/- 0.6% respectively at the 3rd week, while 32.1% +/- 0.3% and 80.6% +/- 0.3% at the 8th week. 2. TIL + rIL-2 + Cy expressed a stronger effect and a longer inhibition time. The IR of TIL + rIL-2 and TIL + rIL-2 + Cy were 20.0% +/- 1.4% and 75.5% +/ 2.5% respeetively at the 8th week (P < 0.01). CONCLUSION: This study demonstrated that TILs from patients with oral carcer possess strong in vivo inhibition on nude mice transplanted tumor, and low dose of cyclophasophamide can enhance the inhibition effect and prolong the inhibition time. PMID- 11774416 TI - [The experimental study of immunization with purified surface protein antigen I/II from streptococcus mutans in BALB/c mice]. AB - OBJECTIVE: To study the immunogenicity and immunoreactivity of purified surface protein antigen I/II from streptococcus mutans. METHODS: Purified antigen I/II was used to immune BALB/c mice by subcutaneous injection route, and S. mutans whole cells were used as comparison. RESULTS: ELISA showed immunization with antigen I/II highly induced both specific serum IgG antibody and specific salivary IgA antibody against antigen I/II (P < 0.01), but immunization with whole cells only induced specific serum IgG antibody (P < 0.05). CONCLUSION: The study suggest purified antigen I/II is an effective candidate vaccine. PMID- 11774417 TI - [Expression of nitric oxide synthase in squamous cell carcinoma of tongue and its prognosis]. AB - OBJECTIVE: To study the expression of nitric oxide synthase (NOS) in squamous cell carcinoma of tongue and its prognosis. METHODS: The NOSI, NOSII and NOSIII of 55 cases of squamous cell carcinoma of tongue were detected by immunohistochemistry. RESULTS: The expressive rates of NOSI, NOSII and NOSIII were 30.9%, 40.0% and 38.2% respectively. There were significant differences between the patients with and without neck nodal metastasis, and between the patients survival more than 5 years and less than 5 years (P < 0.01), There were differences between G1, G2 and G3 and the clinical stages in NOSII (P < 0.05). CONCLUSION: The expression of the NOSI, NOSII and NOSIII in squamous cell carcinoma of tongue is raleted to its prognosis and the NOSII plays a more important role in growth, differentiation, metastatic capability and prognosis of the tumor. PMID- 11774418 TI - [Study on the relationship between the bond absorption of chronic periapical periodontitis and PGE2 and TXB2]. AB - OBJECTIVE: To further study the mechanisms of damages and resorption of bone in chronic periapical periodontitis. METHODS: The quantities and distribution of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were analyzed using radio immunization analysis. RESULTS: The quantities of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were significantly (P < 0.05) higher than those in controls. CONCLUSION: The PGE2 has the close relation with the bone resorption of chronic periapical periodontitis during the whole process. Meanwhile, TXB2 also has certain relation with the bond absorption. The quantities of PGE2 and TXB2 are imbalanced. PMID- 11774419 TI - [Effect of microwave on the dentin of root canal wall]. AB - OBJECTIVE: To investigate the effect of microwave on dentin of root canal wall. METHODS: Ten pairs of clinically sound single rooted premolars(totally 30 root canals: 10 teeth had only one calal and 10 had two canals) were collected. The root canals were treated with microwave of different irradiation energy except one canal of the two canal teeth, they were served as controls. The teeth were dissected longitudinally into two parts and prepared for SEM examination. RESULTS: The microwave of 35 mA irradiated for 3 seconds would not damage the dentin and was safe for clinical usage. But, microwave over 75 mA or with a prolonged irradiation time could damage the dentin of the root canal wall to different extents. The damaged dentin presented incomplete fractures. At the same time, such damage also involved another canal in the same tooth which was not treated with microwave. CONCLUSION: It is necessary to choose a suitable level of energy and control the irradiation time when a root canal is sterilized by microwave. PMID- 11774420 TI - [Study of physiological parameters of velopharyngeal function by nasopharyngeal fibroscope]. AB - OBJECTIVE: Velopharyngeal incompetency (VPI) could be found in certain healthy people when some vowels were produced. Since neither asophia nor organic deformity do they have, it should be considered as physiological VPI. VPI which exists commonly in patients with cleft palate is also an unsatisfactory manifestation after palatoplasty. In order to distinguish between physiological VPI and pathological VPI in patient with cleft palate and establish an objective criterion, it is necessary to assess the occurrence and extent of VPI in healthy people. METHODS: The velopharyngeal function of 890 subjects with normal speech was studied dynamically by nasopharyngeal fiberscope (NPF). Two vowels /i/ and /u/ were examined. The rates of velopharyngeal incompetence (RVPI) of vowel /i/ and /u/ were analyzed. RESULTS: VPI was found in 117 (13.15%) when vowel /i/ was produced. VPI was occurred in 100 (11.24%) when /u/ was produced. The RVPI mean of vowel /i/ is 11.285% +/- 7.248 in 112 subjects, while that of /u/ is 9.066% +/ 6.162 in 96. No significant difference was obtained in age or sex. CONCLUSION: It can be used to evaluate the velopharyngeal function after palatoplasty as physiological parameters. PMID- 11774421 TI - [A retrospective analysis of autogenous alveolar bone grafting in clefts of the lip and palate]. AB - OBJECTIVE: To analyse factors which are able to influence the result of alveolar bone grafting (AABG). METHODS: A retrospective analysis was performed in a group of 54 alveolar cleft patients (30 males and 13 females, total 66 sides) who received AABG. The age range of the patients was 8-44 years. The cleft area was restored with autogenous cancerous bone from iliac crest. All the patients have been followed up for at least three months postoperatively. The result of the bone grafting was evaluated on the radoigraphs. RESULTS: 1. The overall survival rate of AABG was 94%, and clinical successful rate of AABG was 89%; 2. The successful rate of AABG was correlated with the age of the patients. The successful rate of AABG in group of patients above 18-year-old was significantly lower than other groups; 3. With the exception of cleft palate fistula operation, when the AABG was done simulatneously with other cleft lip and palate operations, the successful rate of AABG was not significantly different from that of the sole AABG operation; 4. The successful rate of AABG in patients with cleft lip or incomplete cleft palate was superior to patients with complete cleft palate. CONCLUSION: Forming of excelent bone grafting bed and closely surturing is the key to the success of AABG. PMID- 11774422 TI - [Cleft palate with problems of middle ears]. AB - OBJECTIVE: To gain a clear idea of the function of middle ears and hearing loss in cleft palate. METHODS: 59 cleft palate cases, including 117 ears are investigated by tympanogram and hearing threshold. RESULTS: In 80.4% of patients the function of middle ears are abnormal. 59.4% ears are conductive hearing loss in various degrees. CONCLUSION: Function of middle ears in cleft palate should be regularly examined as early as possible. If it is secretory otitis media, the tympanostomy pressure equalization tubes should be inserted to compensate inadequate function of the eustachian tube so as to avoid adhesive otitis media. The methods for the prevention and reduction of the middle ear problems with cleft palate are also suggested. PMID- 11774423 TI - [The study of presurgical and postsurgical orthodontic treatment of alveolar bone grafting on patients with complete cleft lip and palate]. AB - OBJECTIVE: To investigate the patients who need the orthodontic treatment before and after alveolar bone grafting; the selection of the indications and so on. METHODS: To select 20 patients with cleft lip and palate, each of them is treated by edgewise appliance, light-wire appliance or removable appliance half to one year before the operation. RESULTS: After orthodontic treatment, the patients' maxillary teeth are drawn up in order; the distorted teeth have the right positions; the shape of the arch is normal and the teeth beside the cleft are no longer oblique. All of these give a good space to the grafted bone. CONCLUSION: The orthodontic treatment before and after alveolar bone grafting is an important composition of serial treatment of cleft lip and palate. It not only gives a promise to the successful operation, but also makes patient a better shape and function of the occlusion. PMID- 11774424 TI - [Quantitative analysis of velopharyngeal function by nasopharyngeal fibroscope (NPF)]. AB - OBJECTIVE: To estimate the reliability of the nasopharyngeal fibroscope (NPF) for assessing velopharyngeal function. METHODS: 16 well-pronounced males were examined by NPF which was positioned in different depth. Same procedures were repeated after a week. RESULTS: The results indicated that the rate of velopharyngeal incomptence (RVPI) of NPF had no significant difference when checked in different time and various depths. CONCLUSION: RVPI can be used as a parameter of quantitative analysis for velopharyngeal function, and our results suggested that it is reliable and reproduciable. PMID- 11774425 TI - [The influence of implantal autograft bone in total cleft palate on maxillary growth an experiment study in dogs]. AB - OBJECTIVE: To test the hypothesis that implant autograft bone in total cleft palate at primary cleft palate repair which may resists the disturbance of maxillary growth by cleft and denud bony wound. METHODS: 40 dogs were randomly divided into four groups: three control groups and one experimental group. The first control group was unoperated, the second group had a surgically created cleft plate, the third group also had a surgically created cleft palate. Using a two-flap procedure immidiately, the experiment group had a surgically created cleft palate, but the palate was recontracted by implanting a piece of autograft rib bone with two-flap repair. All animals were sacrificed on the 34th week after operation (43 weeks postnatal). Thirty-four metricranial variables were measured directy from the cleaned skulls. RESULTS: The method is useful for maxillary growth and development by bone implant in total cleft palate, but it can cause maxillary deformity. CONCLUSION: Clinical doctors should be cautious in using the method of primary-delay bone grafting in reparing total cleft of cleft palate. PMID- 11774426 TI - [The study on the acoustic-phonetic features of marginal velopharyngeal closure]. AB - OBJECTIVE: To study the acoustic-phonetic features of the cleft patients with marginal velopharyngeal closure. METHODS: The acoustic-phonetic features of 17 cleft patients with marginal velopharyngeal closure were analyzed with USSA sound spectrograph, contrasted by the features of 28 cleft patients with velopharyngeal incompetence and 18 patients with velopharyngeal competence. RESULTS: The manifestations of single vowel spectrum differ from that of the same vowel in sentence for MVPC patients. There are extra formants or strong nasal formants in a number of vowels spectrums in sentence, while they do not occur on single vowel spectrum. The spike and stop gap in the spectrograms of stops and affricatives may be absent or existing occasionally, and the noise energy in the lowest frequency area in the spectrograms of aspirated consonants may be watched or not. CONCLUSION: Acoustic analysis is very valuable to evaluate the state of marginal velopharyngeal closure. Analyzing the acoustic features of multiple vowels and consonants, and comparing the resonance characteristics of single vowel with the same vowel in continuous speech simultaneously are emphasized. PMID- 11774427 TI - [The use of nasopharyngeal fiberoscope and obturator for treating velopharngeal incompetence]. AB - OBJECTIVE: Using NPF and obturator to treat velopharyngeal incompetence. METHODS: Obturator was made based on the size of the velopharyngeal aperture determined with NPF. RESULTS: All of 45 cases was better in the velopharyngeal function, 15 cases (33%) had normal speech when the obturator was taken away after 2 years. CONCLUSION: This is a good conservative method for treating VPI of cleft palate postsurgery. PMID- 11774428 TI - [Anti-cariogenicity of maceration extract of Momordica grosvenori: laboratory study]. AB - OBJECTIVE: To study the anti-cariogenicity of Momordica grosvenori a kind of natural sweet fruit. METHODS: The turbiding method in laboratory was used to test the influence of the maceration extract of Momordica grosvenori on the growth of Streptococcus mutans (S. mutans), glass rod adhering, and acid production. Sucrose, glocose, fructose, beet sugar were designed to compare with Momordica grosvenori. RESULTS: The growth and fermentation of S. mutans in Momordica grosvenori were significantly lower than these in the other groups includintg beet sugar group (P < 0.01). S. mutans adhering glass rod in Momordica grosvenori was the lowest. CONCLUSION: Momordica grosvenori possesses many advantages: high sweetness and low adherence, and its anti-cariogenicity is better than beet sugar. PMID- 11774429 TI - [Compositional analysis of two metal crowns and its cements unearthed from a Ming Dynasty grave in China by SEM]. AB - OBJECTIVE: To investigate the prosthodontic level of our country in Ming Dynasty (from A. D. 1368 to A. D. 1644) and provide our courtry's history of stomatological development with some details. METHODS: By means of range estimation and SEM, the structure and shape of the metal crowns on the two human teeth which were unearthed from a Ming Dynasty grave, numbered 0754/0046 and stored in Wujin museum of Jiangsu province, as well as the compositions of the crowns and its cements were examined and analysed preliminarily. RESULTS: The two teeth looked like upper anterior teeth and no marks of preparations were observed. The golden-yellow metal crowns might have been hammered and welded into shape. The spectrum analysis of SEM showed the crowns were made from gold-copper alloy and the cements contains Zinc. CONCLUSION: The defects of teeth could have been restored with extra-hard gold-copper alloy and cement luting materials during A. D. 1500-1600 in China. PMID- 11774430 TI - [Orthodontics: development in the past 30 years and present situation]. PMID- 11774431 TI - [Maxillary sinus lifting, bone graft, and simultaneously placement of implants]. AB - OBJECTIVE: To study the effect of maxillary sinus floor lifting by bone graft for immediate implantation. METHODS: 12 maxillary sinus underwent sinus floor bone graft and simultaneously 24 implants olacement. The mean time of follow up was 14 months. RESULTS: There were no implant loose or lost, no clinical complaint of the maxillary sinus area, and X-ray exam showed well osseointegration in 6 months postoperatively. Abnormal sensitivity of chin area were found in 8 patients after bone graft taken from chin, but the sensitivity became normal spontaneously in 3 12 months postoperatively. CONCLUSION: Successful maxillary sinus floor bone graft with simultaneously placement of implant is predictable. PMID- 11774432 TI - [Effect of age on mineralization expression of periodontal ligament cell clones]. AB - OBJECTIVE: To evaluate the effect of age on the expression of mineralized tissue progenitors in the peridontium and the effect of basic fibroblast growth factor (bFGF). METHODS: The periodontal ligament (PDL) tissues that derived from three old and 4 young donors were cultured and cells were cloned. The mineralizing ability were detected with or without bFGF treatment in the presence of dexamethasone. The cell cloning technic was employed in present study. RESULTS: The results indicated that the frequency of mineralized tissue progenitors (old donor: 4.1%) and the numbers of cell clones that mineralized with bFGF treated in the PDL cultures derived from old donors (3.4%) is considerably less than that of cultures obtained from young donors (17.7% and 16.9%). bFGF enhanced the mineralization of cell clone but not the parent population. CONCLUSION: It is concluded that the poor stem cell and progenitors in PDL and the low reaction of progenitors to growth factors in PDL are responsible for the limited regenerative capacity of periodontium in old patient. PMID- 11774433 TI - [The reconstruction of mandible and soft tissue defects with the osteocutaneous free fibula flap]. AB - OBJECTIVE: To find a new material to reconstruct the defects involving mandible and the surrounding soft tissues with the donor site morbidity mild and transient. METHODS: Ten consecutive fibula free flaps were used to reconstruct composite defect of mandible and soft tissue. The average length of the fibular graft was 9.1 cm, and the average size of the cutaneous-flap was 4.5 cm x 6.2 cm. RESULTS: 99mTcO4- scan demonstrated that 9 flaps were survivial (9/10) 2 weeks postsurgery. The function and the contour of the mandible were excellent. The donor site morbidity was mild and transient. CONCLUSION: Fibula has a high density of cortical bone. There is enough bone available to reconstruct mandible defect. The osteocutaneous fibula flap is a new material to reconstruct the composite mandible and soft tissue defects. PMID- 11774434 TI - [Chemotactic response of polymorphonuclear neutrophil to FMLP and IL-8 in rapidly progressive periodontitis patients]. AB - OBJECTIVE: It has been reported that 48%-85% of rapidly progressive periodontitis (RPP) are associated with a defect in polymorphonuclear neutrophil (PMN) chemotactic function. However, some reports failed to detect any defect in PMN chemotaxis in RPP patients. Further, the influence of race on neutrophil function has been suggested. The purpose of the present study was to determine the PMN chemotactic function in Chinese RPP patients. METHODS: Neutrophils were obtained from heparinized peripheral blood of 16 RPP and 14 periodontally healthy control subjects matched for age and sex. Cells were isolated by Percoll discontinuous density gradient centrifugation. Chemotaxis was evaluated using modified Boyden chamber. (N-formyl-methionyl-leucyl-phenylalanine, FMLP) (10(-8) mol/L) and IL-8 (100 micrograms/L) which is a more specific neutrophil chemokines were used in this study. The results were determined by staining the filters followed by visual counting under microscopy at 600 x. Data was analyzed using the Students' t test and the value of RPP was compared with that of control subjects(> mean +/- 2s or < mean +/- 2s). RESULTS AND CONCLUSION: The results showed all RPP patients had normal PMN chemotactic behavior. PMID- 11774435 TI - [Experimental study of parotid gland injected with gentian violet]. AB - OBJECTIVE: The Gentian Violet was used for treating the chronic parotitis since 1960's, but the dosage and the histologic changes of the tissues were undefined until now. We try to study the histologic changes of the salivary glands, heart, liver and kidneys after large volume of gentian violet was injected into the parotid gland through the duct. METHODS: 5 ml of Gentian Violet was injected to each side of 6 dogs. The macropathologic and histologic examination of the salivary glands, heart, liver and kidneys were performed at 30 min, 60 min, 120 min, 21 days and 9 months separately after the perfusion. RESULTS: Local swelling was obvious in two or three days after infusion and subsided in one week in most of the dogs. Degeneration of the gland took place after 20 days. After 9 months, the parotid gland tissues were replaced by the connective tissues. On the other hand, no histologic change was observed in heart, liver and kidney in the investigation. CONCLUSION: The Gentian Violet can cause degeneration of the parotid gland including the duct and replaced by connective tissues later. There is no obvious changes were noted in other organs. PMID- 11774436 TI - [The inhibiting effect of glycyrrhizin on proliferation of the mice submandibular gland fibrosarcoma cell line in vitro]. AB - OBJECTIVE: To study the inhibiting effect of glycyrrhizin on proliferation of the cell line of mice submandibular gland fibrosarcome in vitro. METHODS: Light and electronic microscope examination, proliferative state of cells and cycle phase analysis were used. RESULTS: Administration of glycyrrhizin above 600 mg/L could inhibit cell proliferation, and the effect was dose and time dependent. The morphological change of the cell line affected by glycyrrhizin could be seen with light and electronic microscope. Cell cycle phase analysis showed gLy-cyrrhizin gould stop cells shifting from G1 to S phase. CONCLUSION: The Lowest inhibition concentration of glycyrrhizin to the cell line was above 600 mg/L, The antineoplastic effect of glycyrrhizin was possibly accomplished by interfering metabolism of G1 phase cells or/and blocking initiation of DNA synthesis. PMID- 11774437 TI - [Relationship between elastase activity and leukocyte counts in gingival crevicular fluid]. AB - OBJECTIVE: To determine the relationship among the elastase(EA) activity in the supernatant (EA-s), and in the pellet (EA-p) after centrifuge, and polymorphonuclear leukocyte (PMN) counts in gingival crevicular fluid. METHODS: Gingival crevicular fluid (GCF) was sampled with filter paper strips by intra pocket method to determine EA levels and then with gingival crevicular washings after 24 hours at the same site for PMN counting. The levels of EA-s and EA-p were determined seperately using the subtract Meosuc-ala-ala-val-pro-NA. PMNs at the same site were counted with light microscope. RESULTS: The research demonstrated significantly positive correlation among EA-s and EA-p per site and the PMN counts in GCF (P < 0.001). CONCLUSION: GCF-EA-p per site could reflect the amount of PMNs collected from the pockets, and EA can be the marker of PMN in GCF. PMID- 11774439 TI - [The histopathological analysis of root fractures of molars with vital pulp]. AB - OBJECTIVE: To analyze the causes of root fractures by examining fractured roots histologically. METHODS: Fractured roots were sectioned for microscopic analysis in conventional histological ways. RESULTS: 1. Among 18 roots cut transversely were 14 flat roots with 2 canals, 2. most of the fractures passed along incremental line in dentine, 3. of the longitudinally sectioned roots, areas of marked resorption were visible on the dentine within the fractures of apical third, and 4. repairs of both soft and hard tissues were observed in the fracture spaces. CONCLUSION: The fractures of roots were associated with morphology of roots and incremental lines in dentine. The repair and cure of fractured roots were not impossible. PMID- 11774438 TI - [Initial evaluation of mass lesions in the head and neck with enhanced (Gd-DTPA) MR imaging]. AB - OBJECTIVE: To evaluate mass lesions of the head and neck with enhanced (Gd-DTPA) MR imaging. METHODS: Twenty-five of patients (13 males and 12 females; mean: 46.9 years) suffered from mass lesions of the head and neck inspected with Gd-DTPA MR imaging, 17 cases were certificated histopathologically and followed up. The examinations of all patients were carried out with plain T1-weighted spin-echo sequences (TR/TE = 500-600/30), and Gd-DTPA enhanced T1-weighted spin-echo sequences (TR/TE = 300-500/30). RESULTS: Comparing with plain MR imaging, 23 mass lesions were stained on SE T1-weighted images (23/25) after intravenous administration of Gd-DTPA. The enhanced patterns of these lesions might be divided into homogeneous (10/23) and inhomogeneous (13/23). Gd-DTPA was helpful in delineating extent of 16 mass lesions. CONCLUSION: The various morphologic manifestations of enhanced lesions have close relations with their own intimate structures. The enhanced MR imaging is superior to plain MR imaging on displaying the inner structure and extent of diseases and estimating the recurrent lesions. PMID- 11774440 TI - [Experimental study of hydroxyapatite (HA) granules filled around the titanium implant]. AB - OBJECTIVE: To compare the diference of the bone formation between immediate and delayed implantation, and evaluate the role of the hydroxyapatite (HA) in immediate implantation. METHODS: HA coated titanium implants were implanted into the femurs of adult dogs, the diameter of the socket was 6.5 mm and 3.5 mm respectively, HA coated titanium implants (all with the diameter of 3.5 mm) were placed into the latter sockets, and was considered to be the model of delayed implantation. The implantation in the 6.5 mm socket were considered to be the model of immediate implantation. The immediate implantation was divided into two groups, HA granules were filled in between the bone and implant in one group, and no HA particles was filled in another group. Animals were killed at 1,2,3 and 4 months post operation. RESULTS: Immature new bone formation was found on all specimens one month after implantation, and the amount of new bone formation in HA particles filled group was much more than that group without HA particles. In the HA granules group, there was no marked difference from the group of implantation in 3.5 mm socket. Mature new bone was observed four months later after operation, and no marked difference was found in the amount of new bone between HA granules filled implantation in 6.5 mm socked and implantation in 3.5 mm socket. CONCLUSION: Implantation of HA granules is helpful to the stability of the implant and plays a role in the healing of implant with surrounding bones. PMID- 11774441 TI - [Effect of tea on fluoride in plaque and saliva]. AB - OBJECTIVE: To evaluate whether tea drinking in a Chinese way in the Chinese population would affect fluoride in plaque and saliva. METHODS: Two groups of students were involved. Group 1, 41 subjects, did not drink tea regularly. Group 2, 34 subjects, drank tea every day in a very regular way. During a study period of three weeks, Group 2 was requested to drink selected (known fluoride concentration) types of tea, and subdivided by the type of tea they drank into two subgroups, Groups 2a and 2b. Group 2a drank lower fluoride tea, while Group 2b drank higher fluoride tea. Plaque and saliva samples were collected at the 2nd and the 3rd end of week, respectively. Fluoride levels were determined with fluoride selective electrode. RESULTS: Both plaque and saliva fluoride were higher in the tea drinking group compared with non-tea drinking group. Plaque fluoride in tea drinking group at the end of three week was significantly higher than the value of non-tea drinking group (t test, P = 0.02). In tea drinking group, three week plaque fluoride was higher than two week plaque. Plaque fluoride level was also significantly corresponded to fluoride in tea. Drinking higher fluoride tea resulted in higher fluoride in plaque. But saliva fluoride was not shown the correlation with tea. CONCLUSION: Tea is an important fluoride source. Plaque is a main resorvior of fluoride. Saliva has not the ability to store fluoride up. When considering tea as a fluoride source, the type of tea which may contain different concentration of fluoride should be borne in mind. PMID- 11774442 TI - [The effect of retinoic acid on crown morphogenesis of mouse tooth germs in vitro]. AB - OBJECTIVE: To study the effects of retinoic acid on crown morphogenesis of early tooth germs. METHODS: Mouse tooth organ culture model was used and the functions of different retinoic acid concentration on the first mandibular molar germs of 14-day old mouse embryo were examined. RESULTS: The first mandibular molar germ of 14-day old mouse was at the bud stage. After 6 days culture, tooth germs in culture medium (not containing retinoic acid) developed from bud stage to bell stage and formed normal cusps. The morphogenesis of tooth germs in medium containing 1 x 10(-7) mol/L retinoic acid was similar to molar germs in the medium without retinoic acid. When the concentration of retinoic acid increased to 1 x 10(-6) mol/L, the mouse tooth germs still developed from bud stage to bell stage, but normal cusps was not formed. CONCLUSION: The results suggest that high concentration of retinoic acid alter crown morphogenesis of tooth germs. PMID- 11774443 TI - [Investigation of the clinical value of total salival flow rates]. AB - OBJECTIVE: To investigate clinical value of total saliva flow rates. METHODS: The symptom of dry mouth was correlated with unstimulated (UWSFR) and stimulated (SWSFR) whole saliva flow rates on chewing medical paraffin in 62 patients with dry mouth complaints (30 with Sjogren's syndrome, 32 with sialosis) and 23 controls. The symptom of dry mouth was classified into 0,1,2,3,4 according to a treatment emergent symptom scale (TESS). UWSFR and SWSFR were determined after fasting in the morning. RESULTS: UWSFR was (0.070 +/- 0.089) ml/min in Sjogren's syndrome, (0.175 +/- 0.115) ml/min in sialosis, (0.330 +/- 0.188) ml/min in controls. SWSFR was (0.709 +/- 0.720) ml/min in Sjogren's syndrome, (1.561 +/- 0.867) ml/min in sialosis, (1.894 +/- 0.661) ml/min in controls. A highly significant correlation was found between TESS score and UWSFR and between TESS score and SWSFR. Only UWSFR was decreased in the patients with a TESS score of 1 or 2, while both UWSFR and SWSFR were significantly decreased in patients with TESS scores of 3,4. CONCLUSION: It is concluded that UWSFR is more sensitive in relation to dry mouth complaints than SWSFR, and that a mild dry mouth is mainly related to decreased UWSFR. PMID- 11774444 TI - [Clinical study and denominate of traumatic herniation of corpus adiposum buccae]. AB - OBJECTIVE: To deepen the recognition, and provide the evidence for rational name of traumatic herniation of corpus adiposum buccae. METHODS: 10 clinical cases of traumatic herniation of corpus adiposum buccae were studied. Simulat experiment on 6 fresh corpses (12 sides) were performed dissected immediately after bump (hitting) type and stab (thrusting) type of herniation of corpus adiposum buccae. RESULTS: In one side bump type and 5 sides stab type successful experiments, the buccal protuberance of masticatory fat pads (namely corpus adiposum beccae) were herniated into the mouth, with the shape, size, and position simulated with the herniated tissue of the clinical case. CONCLUSION: The herniated tissue of clinical case is the corpus adiposum buccae but not the buccal fat pad, and the rational name should be traumatic herniation of corpus adiposum buccae. PMID- 11774445 TI - [The study on the correlation between the effect of dental appliances on OSAS and the morphology of upper airway and craniofacial structures]. AB - OBJECTIVE: The purpose of this present study was to evaluate the effectiveness of dental appliances on OSAS by combining the use of overnight polysomnography and cephalometry. METHODS: 22 OSAS adult patients wore the dental appliances designed by authors. The association between the improvement of respiratory variables and the cephalometric variables were investigated on the basis of linear correlation analysis. We also classified the subjects by AI of post-treatment to analyze the morphological disparity of upper airway and craniofacial structures among the groups. RESULTS: There was no significant correlation between the improvement of AI and the morphology of the upper airway and its surrounding soft structures, but there existed significant linear correlation between the improvement of AI and the morphology of the craniofacial skeletal structure. The improvement of the lowest SaO2 was only correlated significantly with the body length of the mandible and the anteroposterior position of the base of tongue. However, the improvement of the RDI wasn't associated significantly with any morphological variables. In addition, there were morphological differences among the different groups. CONCLUSION: The above findings suggested that the effectiveness of dental appliance on OSAS is mainly associated with craniofacial skeletal structures, but no correlation existed between the sagittal dimension of upper airway and the effectiveness. PMID- 11774446 TI - [Activation of insulin-like growth factor 1 gene expression in growing rat condyle by functional mandibular protrusion]. AB - OBJECTIVE: We studied the changes of the IGF-1 mRNA expression in condylar cartilage to elucidate the biomolecular mechanism of mandibular advancement. METHODS: Sixty 5-week-old male rats were randomly divided into experimental and control groups. The mimic functional appliances were used in experimental group. The rats were sacrificed after 1, 3, 7, 14, 21 and 28 days to study the expression of IGF-1 mRNA by in situ hybridization. RESULTS: The results showed IGF-1 mRNA expression in the condylar cartilage. The transitional and maturational layers had the most abundant IGF-1 mRNA, and the IGF-1 mRNA abundance of germinal layer is higher than that of synovial and fibrous layers. Functional mandibular protrusion activated the IGF-1 mRNA expression and it began to increase after 3 days of the experiment, and the changes were most significant in 7-14 days. CONCLUSION: This suggested that the condylar cartilage growth and remolding after functional protrusion might be caused by IGF-1 gene expression activation. PMID- 11774447 TI - [An experimental study on the changes of estrogen receptor in the condylar cartilages with DCC method in rats after functional mandibular protrusion]. AB - OBJECTIVE: The purpose of the study was to evaluate the estrogen receptors (ER) in the condylar cartilages in relation to the hyperplasia, hypertrophy and functional adaptive remodelling after functional mandibular protrusion. METHODS: Dextran-coated charcoal (DCC) method was performed to quantitively detect the level of ER. Fifty female rats of 4-week-old were selected and simulated functional appliances were used to guide their mandibles. The rats were sacrificed after 3 days, 1 week, 2 week, 3 week and 4 week. RESULTS: The results showed ER do exist in the condylar cartilages of the rats, with the highest levels during their actively proliferative period and the amount of ER was increased significantly after functional mandibular protrusion. CONCLUSION: It is suggested that ER has a close relationship with the hyperplasia, hypertrophy of the condylar cartilages and plays a very important role in the adaptive remodelling mechanism after functional mandibular protrusion. PMID- 11774448 TI - [1,25(OH)2 vitamin D3 induces IL-1 alpha mRNA expression from osteoblastic-like and bone marrow co-culture cells]. AB - OBJECTIVE: The purpose of this research is to investigate the relationship between 1,25(OH)2 Vitamin D3[1,25(OH)2D3] and Interleukin-1 (IL-1) in regulating osteoclast formation. The result may enrich our knowledge about biological mechanisms of periodontal tissue remodeling during orthodontic tooth movement. METHODS: We found IL-1 alpha mRNA expression in bone marrow and osteoblastic cell co-cultures by semi-quantitative RT-PCR. RESULTS: 1,25(OH)2D3 increased IL-1 alpha mRNA expression from this co-culture cells in a dose dependent manner, and the expression reached its peak in day 2 and decreased thereafter. CONCLUSION: These results demonstrate that IL-1 alpha involves in osteoclast formation induced by 1,25(OH)2D3. And we propose IL-1 alpha may stimulate the proliferation of osteoclast progenitor during the first 4 days of total 6 days culture period. PMID- 11774449 TI - [A computer system for bone age measurement of hand radiographs]. AB - OBJECTIVE: This study was to development a computer system for assessing bone age which would analyse children's growth level accurately and quickly. METHODS: It used the standards of estimating skeletal maturity for Chinese (CHN) scoring method to assess the bone age of Chinese children. We applied image enhancement techniques for imprving the quality of the hand-wrist radiographs, while an automated system was developed to implement this method. RESULTS: Users could get a clear and reliable radiograph through image processing, compare each bone of the hand-wrist radiograph with that of the scanned image of the standard radiographs, then generate the stage of bone maturity. The computer would give out individual and total bone score and a value of bone age. CONCLUSION: This system implemented evaluation of bone age rapidly and accurately, it would help orthodontist to choose the best time of treatment. PMID- 11774450 TI - [An analysis of curative effect of activator in treating Class II division 1 malocclusion]. AB - OBJECTIVE: To analyze the results of class II division 1 malocclusion treated by activator. METHODS: Sixteen growing patients, who were diagnosed as class II division 1 malocclusion, were evaluated by McNamara analysis. RESULTS: The activator affects the growth of mandible positively and inhibits the growth of the maxilla. CONCLUSION: The activator can treat class II division 1 malocclusion effectively, which can be perceived by McNamara analysis directly. PMID- 11774451 TI - Big nidovirus genome. When count and order of domains matter. PMID- 11774452 TI - Susceptibility of murine CNS to OC43 infection. PMID- 11774453 TI - Caspase inhibitors block MHV-3 induced apoptosis and enhance viral replication and pathogenicity. PMID- 11774454 TI - MHV neuropathogenesis: the study of chimeric S genes and mutations in the hypervariable region. PMID- 11774455 TI - Mutation of the immunodominant CD8+ epitope in the MHV-4 spike protein. PMID- 11774456 TI - Spread of hemagglutinating encephalomyelitis virus (HEV) in the CNS of rats inoculated by intranasal route. PMID- 11774457 TI - Demyelination determinants in the S gene of MHV. PMID- 11774459 TI - Neurovirulence for mice of soluble receptor-resistant mutants of murine coronavirus JHMV. PMID- 11774458 TI - Role of the spike protein in murine coronavirus induced hepatitis: an in vivo study using targeted RNA recombination. PMID- 11774460 TI - Infection of hemagglutinating encephalomyelitis virus (HEV) at the visual pathways of rats. PMID- 11774461 TI - The effect of the T1087N S gene mutation on MHV-A59 pathogenesis. PMID- 11774462 TI - Pathogenesis of fusion deficient recombinant mouse hepatitis viruses. AB - In this study we have demonstrated that recombinant viruses carrying the amino acid mutations Q1067H, Q1094H, and L1114R were unable to induce fusion at neutral pH, replicated more efficiently in L2 cells, and that infection was delayed by ammonium chloride. These results suggest that the R120/R121 recombinants most likely use the endosomal pathway to enter cells. In this sense they are similar to the pH-dependent MHV-4 variant OBLV60. We were able to observe an attenuated virulence in vivo, despite the fact that our R120/R121 recombinants replicated to comparable (IC) or higher (IN) titers than the S4R29 recombinant in the brain. Preliminary results showed that the level of inflammation observed in infected mice is consistent with the attenuated virulence, but they cannot be explained by the high titers of replication. PMID- 11774463 TI - Programmed cell death in MHV-induced demyelination. PMID- 11774464 TI - In vitro properties and pathogenesis of A59/MHV4 chimeric mouse hepatitis viruses. PMID- 11774465 TI - Receptor specificity and receptor-induced conformational changes in mouse hepatitis virus spike glycoprotein. PMID- 11774466 TI - Murine coronavirus spike glycoprotein. Receptor binding and membrane fusion activities. PMID- 11774468 TI - Human coronavirus HCoV-229E enters susceptible cells via the endocytic pathway. PMID- 11774467 TI - Molecular epidemiology and evolution of equine arteritis virus. PMID- 11774469 TI - Addition of a single glycosylation site to hAPN blocks human coronavirus-229E receptor activity. PMID- 11774470 TI - Effects of amino acid insertions in the cysteine-rich domain of the MHV-A59 spike protein on cell fusion. PMID- 11774471 TI - Involvement in fusion activity of an epitope in the S2 subunit of murine coronavirus spike protein. PMID- 11774472 TI - Are intestinal mucins involved in the pathogenicity of transmissible gastroenteritis coronavirus? PMID- 11774473 TI - Biochemical properties and processing of the three major structural proteins of PRRS virus expressed by recombinant adenoviruses. Structural, functional and community aspects. PMID- 11774474 TI - Inefficient infection of soluble receptor-resistant mutants of murine coronavirus in cells expressing MHVR2 receptor. PMID- 11774475 TI - A study on mouse hepatitis virus receptor genotype in the wild mouse. PMID- 11774476 TI - Arterivirus RNA synthesis dissected. Nucleotides, membranes, amino acids, and a bit of zinc.... PMID- 11774477 TI - Genetic and antigenic stability of PRRS virus in pigs. Field and experimental prospectives. PMID- 11774478 TI - Guanosine triphosphatase activity of the human coronavirus helicase. PMID- 11774479 TI - A strategy for the generation of an infectious transmissible gastroenteritis coronavirus from cloned cDNA. PMID- 11774480 TI - Processing of the replicase of murine coronavirus: papain-like proteinase 2 (PLP2) acts to generate p150 and p44. PMID- 11774481 TI - Comparison of replicase localization in different types of mouse hepatitis virus (MHV)-infected cells. PMID- 11774483 TI - Further identification and characterization of products processed from the coronavirus avian infectious bronchitis virus (IBV) 1a polyprotein by the 3C-like proteinase. PMID- 11774482 TI - Exploiting DNA immunization to generate polyclonal antisera to coronavirus replicase proteins. PMID- 11774484 TI - CD8 T cell mediated immunity to neurotropic MHV infection. PMID- 11774485 TI - Coronavirus derived expression systems. Progress and problems. PMID- 11774486 TI - Appearance of novel PRRSV isolates by recombination in the natural environment. PMID- 11774487 TI - The CXC chemokines IP-10 and Mig are essential in host defense following infection with a neurotropic coronavirus. PMID- 11774488 TI - Regulation of matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) genes during JHMV infection of the central nervous system. PMID- 11774489 TI - IFN-gamma secreted by virus-specific CD8+ T cells contribute to CNS viral clearance. PMID- 11774490 TI - The role of CD4 and CD8 T cells in MHV-JHM-induced demyelination. PMID- 11774491 TI - Acute CNS infection is insufficient to mediate chronic T cell retention. PMID- 11774492 TI - Generation from multiple sclerosis patients of long-term T-cell clones that are activated by both human coronavirus and myelin antigens. PMID- 11774493 TI - The role of B cells in mouse hepatitis virus infection and pathology. PMID- 11774494 TI - B cell mediated lysis of JHMV infected targets. PMID- 11774495 TI - Predicted RNA folding suggests PRRSV major and heteroclite subgenomic transcripts result from polymerase switching at unpaired nucleotides. PMID- 11774496 TI - Polyclonal activation of B cells by lactate dehydrogenase-elevating virus is mediated by N-glycans on the short ectodomain of the primary envelope glycoprotein. PMID- 11774497 TI - Influence of changes in the population of target cells and appearance of specific antibodies on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs. PMID- 11774498 TI - Monoclonal antibody directed against a membranous protein of MARC-145 cells blocks infection by PRRSV. PMID- 11774499 TI - Detection of antibodies to the nucleocapsid protein of PRRS virus by a competitive ELISA. PMID- 11774500 TI - Enhancement of defective RNA expression vectors as potential vaccine delivery systems for avian infectious bronchitis virus. PMID- 11774501 TI - A virus-neutralising monoclonal antibody expressed in the milk of transgenic mice. PMID- 11774502 TI - Nidovirus genome replication and subgenomic mRNA synthesis. Pathways followed and cis-acting elements required. PMID- 11774503 TI - Regulation of mouse hepatitis virus RNA synthesis by heterogeneous nuclear ribonucleoprotein A1. PMID- 11774504 TI - Gill-associated virus of Penaeus monodon prawns. Molecular evidence for the first invertebrate nidovirus. PMID- 11774505 TI - Role of hnRNP A1 in coronavirus RNA synthesis. PMID- 11774506 TI - Expression of transcriptional units using transmissible gastroenteritis coronavirus derived minigenomes and full-length cDNA clones. PMID- 11774507 TI - Identification of the mutations responsible for the phenotype of three MHV RNA negative ts mutants. PMID- 11774508 TI - MHV subgenomic negative strand function. PMID- 11774509 TI - Requirement of the poly(A) tail in coronavirus genome replication. PMID- 11774510 TI - A simple strategy to assemble infectious RNA and DNA clones. PMID- 11774511 TI - Chromatography of mouse hepatitis virus replicative intermediate and replicative form RNA. PMID- 11774512 TI - Elucidation of the genomic nucleotide sequence of bovine coronavirus and analysis of cryptic leader mRNA fusion sites. PMID- 11774513 TI - Mouse hepatitis virus minus-strand templates are unstable and turnover during viral replication. PMID- 11774514 TI - Mutagenesis of the 3'42 nucleotide host protein binding element of the MHV 3'UTR. PMID- 11774515 TI - Use of an infectious bronchitis virus D-RNA as an RNA vector. PMID- 11774517 TI - Characterization of an arterivirus defective interfering RNA. Replication and homologous recombination. PMID- 11774516 TI - Use of defective RNAs containing reporter genes to investigate targeted recombination for avian infectious bronchitis virus. PMID- 11774518 TI - Packaged heteroclite subgenomic RNAs of PRRSV. PMID- 11774519 TI - Cloning of a transmissible gastroenteritis coronavirus full-length cDNA. PMID- 11774520 TI - Functional IBV minigenomes generated by recombinant fowl pox viruses for use in IBV-targeted recombination studies. PMID- 11774521 TI - Heterogeneity of subgenomic mRNAs of a mutant mouse hepatitis virus strain JHM2C. PMID- 11774522 TI - Mapping of the RNA-binding domain of the porcine reproductive and respiratory syndrome virus nucleocapsid protein. PMID- 11774523 TI - Sequences required for replication and packaging of IBV RNA. PMID- 11774524 TI - Characterization of temperature-sensitive (ts) mutants of coronavirus infectious bronchitis virus (IBV). PMID- 11774525 TI - Identification of a noncanonical transcription initiation site for transcription of a subgenomic mRNA of mouse hepatitis virus. PMID- 11774526 TI - Biological and molecular characteristics of an HEV isolate associated with recent acute outbreaks of encephalomyelitis in Quebec pig farms. PMID- 11774527 TI - Infectious bronchitis virus envelope protein targeting: implications for virus assembly. PMID- 11774528 TI - Characterization of nucleocapsid-M protein interaction in murine coronavirus. PMID- 11774529 TI - Production, characterization, and uses of monoclonal antibodies against porcine reproductive and respiratory syndrome virus 3' untranslated region and nucleoprotein RNA binding proteins. PMID- 11774530 TI - The membrane M protein of the transmissible gastroenteritis coronavirus binds to the internal core through the carboxy-terminus. PMID- 11774531 TI - Physical interaction between the membrane (M) and envelope (E) proteins of the coronavirus avian infectious bronchitis virus (IBV). PMID- 11774532 TI - Mitochondrial aconitase binds to the 3'-UTR of mouse hepatitis virus RNA. PMID- 11774533 TI - The cell biology of coronavirus infection. AB - The ability to obtain entire volume data on infected cells will allow us to define much more accurately the interactions of viral proteins with host cell structures such as ER, Golgi, and cytoskeletal elements. In addition, the demonstrated ability to express viral proteins fused to fluorescent markers in in live cells will allow us to follow specific proteins or complexes during the course of infection and to determine if exogenously expressed proteins are able to target to sites of active viral replication. This in turn will allow new approaches to the study of viral and cellular protein-protein interactions, as methods to study the biology and pathogenesis of MHV infection at a cellular level. Finally, the approaches described here will allow us to define protein complementation of defective viruses at a cellular level, rather than being dependent on population measurements of RNA, protein, or progeny virus. By combining these approaches with available biochemical and molecular biological approaches and the emerging reverse genetic and recombinant genetic approaches, rapid progress in understanding the details of coronavirus-cell interactions should be possible. PMID- 11774535 TI - Specific cleavage of 28S ribosomal RNA in murine coronavirus-infected cells. PMID- 11774534 TI - Induction of apoptosis in murine coronavirus-infected 17Cl-1 cells. PMID- 11774536 TI - Homotypic interactions of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus (PRRSV). PMID- 11774537 TI - Identification of specific variations within the HE, S1, and ORF4 genes of bovine coronaviruses associated with enteric and respiratory diseases in dairy cattle. PMID- 11774538 TI - Interactions of cellular proteins with the positive strand of 3'-untranslated region RNA and the nucleoprotein gene of porcine reproductive and respiratory syndrome virus. PMID- 11774539 TI - Cloning and identification of MARC-145 cell proteins binding to 3'UTR and partial nucleoprotein gene of porcine reproductive and respiratory syndrome virus. PMID- 11774540 TI - Identification of cell proteins that bind to the SHFV 3' (+)NCR. PMID- 11774541 TI - MHV-A59 gene 1 proteins are associated with two distinct membrane populations. PMID- 11774542 TI - Differential expression of tumor necrosis factor in primary glial cell cultures infected with demyelinating and non-demyelinating MHVs. PMID- 11774543 TI - Infectious bronchitis virus nucleocapsid protein interactions with the 3' untranslated region of genomic RNA depend on uridylate bases. PMID- 11774544 TI - Induction of apoptosis in MRC-5, diploid human fetal lung cells after infection with human coronavirus OC43. PMID- 11774545 TI - Effects of heparin on the entry of porcine reproductive and respiratory syndrome virus into alveolar macrophages. PMID- 11774546 TI - Genetic variation of ORFs 3 and 4 of equine arteritis virus. PMID- 11774547 TI - Apoptosis in the lungs of pigs during an infection with a European strain of porcine reproductive and respiratory syndrome virus. PMID- 11774548 TI - Full-length genomic sequence of bovine coronavirus (31 kb). Completion of the open reading frame 1a/1b sequences. PMID- 11774549 TI - Analysis of CNS inflammatory responses to MHV. Role of spike determinants in initiating chemokine and cytokine responses. PMID- 11774550 TI - Analysis of nonessential gene function in recombinant MHV-JHM. Gene 4 knockout recombinant virus. PMID- 11774551 TI - Persistence of porcine reproductive and respiratory syndrome in pigs. PMID- 11774552 TI - The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-gamma deficient mice is parallel to viral replication in hepatocytes in vitro. PMID- 11774553 TI - Interactions between dendritic cells. PMID- 11774554 TI - Neural regulation of dendritic cell function. PMID- 11774555 TI - A central role for heat shock proteins in host deficiency. PMID- 11774556 TI - Allele specific regulation of cytokine genes: monoallelic expression of the IL-1A gene. PMID- 11774557 TI - Effect of polysaccharide sulfates on the production of interleukin-8 in an ex vivo model. PMID- 11774558 TI - Coordination of interleukin-6 biology by membrane bound and soluble receptors. PMID- 11774559 TI - Molecular characterization of gut T cell precursors in euthymic and athymic mice. PMID- 11774560 TI - Termination and modulation of IL-6-type cytokine signaling. PMID- 11774561 TI - Cytokine-induced STAT signalling through the cytoplasmic compartment. PMID- 11774563 TI - Interleukin-6, tumor necrosis factor alpha and interferon gamma in patients with anorexia nervosa. PMID- 11774562 TI - Cytokine-mediated growth inhibition of human melanoma cells. PMID- 11774564 TI - Interleukin-1 system in testis--quantitative analysis. Expression of immunomodulatory genes in male gonad. PMID- 11774565 TI - Mapping genes underlying complex disorders: progress on IgA deficiency and common variable immunodeficiency. PMID- 11774566 TI - Ataxia-telangiectasia. PMID- 11774567 TI - Gene therapy of severe combined immunodeficiencies. PMID- 11774568 TI - Immune reconstitution after highly active anti-retroviral treatment of HIV infection. PMID- 11774569 TI - Dissimilarity of clinical signs with parameters characterizing immune system. PMID- 11774570 TI - The role of Fc receptors and complement in autoimmunity. PMID- 11774571 TI - Effect of Hsp70-peptide complexes generated in vivo on modulation EAE. PMID- 11774573 TI - Modification of humoral antisperm response. PMID- 11774572 TI - Gene transfer of protective cytokines in rheumatoid arthritis. PMID- 11774574 TI - Immunologic mechanisms of allergen-specific immunotherapy. PMID- 11774575 TI - CRTH2: marker for the detection of human Th2 and Tc2 cells. PMID- 11774576 TI - Phosphorothioate oligonucleotides: looking for the motif(s) possessing immunostimulatory activities in humans. PMID- 11774577 TI - Disorders in mononuclear phagocytes and reduced glutathione and their correction in Chernobyl children with recurrent respiratory infections and chronic inflammatory focal lesions. PMID- 11774578 TI - Adoptive transfer of mucosal T cells or dendritic cells from animals fed with cholera toxin B subunit alloantigen conjugate induces allogeneic T cell tolerance. PMID- 11774579 TI - Total body irradiation before bone marrow transplantation: aims and results. PMID- 11774580 TI - Statins as immunomodulatory drugs. PMID- 11774581 TI - Phage display of epitopes from HIV-1 elicits strong cytolytic responses in vitro and in vivo. PMID- 11774582 TI - Oral immunization of human with transgenic lettuce expressing hepatitis B surface antigen. PMID- 11774583 TI - Nasal administration of Schistosoma mansoni egg antigens-cholera toxin B subunit conjugate to infected mice reduces immunopathology and mortality. PMID- 11774584 TI - GILZ, a glucocorticoid hormone induced gene, modulates T lymphocytes activation and death through interaction with NF-kB. PMID- 11774585 TI - Anti-influenza vaccination changes expression of CD45 isoforms on peripheral blood NK cells of the elderly. PMID- 11774586 TI - Presence and functions of immune components in the tumor microenvironment. PMID- 11774587 TI - Expression of TCR zeta chain of tumor associated lymphocytes from malignant pleural effusions. PMID- 11774588 TI - Cytochrome c is rapidly extruded from apoptotic cells and detectable in serum of anticancer-drug treated tumor patients. PMID- 11774589 TI - CD 56 (N-CAM) antigen and mRNA expression in human endocrine glands. PMID- 11774590 TI - Glycodendrimeric ligands of c-type lectin receptors as therapeutic agents in experimental cancer. PMID- 11774591 TI - Exosomes in cancer immunotherapy: preclinical data. PMID- 11774592 TI - Bone marrow dendritic cell-based anticancer vaccines. PMID- 11774593 TI - Dendritic cell-based vaccines for therapy of HPV16-induced tumours. PMID- 11774594 TI - Cytokine gene transfection for autologous and allogeneic melanoma vaccines. PMID- 11774595 TI - Brain tumor treatment with IL-2 and IL-12 producing autologous cancer cell vaccines. PMID- 11774596 TI - IL-11 is a potent anti-melanoma factor. PMID- 11774597 TI - IL-6 and GM-CSF in tumor rejection model of renal cell cancer. PMID- 11774598 TI - The effects of peritumoral therapeutic vaccination with IL-2-secreting cells on growth of MC38 colon tumours in mice, local NO production and sentinel lymph node cells activation. PMID- 11774599 TI - Improving the retroviral vector (RV) systems for immunotherapy of cancer. PMID- 11774600 TI - Tumor immunity in mice immunized with fibroblasts transfected with tumor DNA. PMID- 11774601 TI - T cell response to tumor antigens and its therapeutic use in cancer patients. PMID- 11774602 TI - Tyrosine phosphorylation of PICOT and its translocation to the nucleus in response of human T cells to oxidative stress. PMID- 11774603 TI - Humoral responses to melanoma vaccine, genetically modified with interleukin 6 and soluble interleukin 6 receptor. PMID- 11774605 TI - Flow cytometric cytotoxicity assay with GFP gene modified target cells. PMID- 11774604 TI - Clinical studies of human papilloma vaccines in cervical cancer. PMID- 11774606 TI - Flow and video-imaging cytometry--usefulness of DNA ploidy measurements in diagnosis of malignant melanoma. PMID- 11774607 TI - The molecular specificity of IgG-Fc interactions with Fc gamma receptors. PMID- 11774608 TI - CD3-dependent regulation of early TCR beta gene expression in mainstream alpha beta and NK alpha beta T cell development. PMID- 11774609 TI - Regulation of myeloid cell proliferation and survival by p75/AIRM1 and CD33 surface receptors. PMID- 11774610 TI - X-linked lymphoproliferative disease: the dark side of 2b4 function. PMID- 11774612 TI - Regulation of transporters associated with antigen processing (TAPs) by nucleotide binding to, and hydrolysis by, Walker consensus sequences. PMID- 11774611 TI - Role of tapasin in MHC class I antigen presentation in vivo. PMID- 11774613 TI - The AIR-1 encoded class II transactivator (CIITA): the master coordinator of MHC class II gene expression and .. more. PMID- 11774615 TI - Rightful recipients. Ethics and the allocation of organs. PMID- 11774614 TI - Major histocompatibility complex class II (MHC II) expression during development of human fetal brain and haemopoietic organs. PMID- 11774616 TI - Make of our hearts one heart. PMID- 11774617 TI - Redeeming work. PMID- 11774618 TI - Transplant taboo. PMID- 11774619 TI - Suspect sources. PMID- 11774620 TI - Lifelines for diabetics. PMID- 11774621 TI - Preventing rejection. PMID- 11774622 TI - Living donor liver transplantation. PMID- 11774623 TI - Laparoscopic donor nephrectomy. The University of Minnesota experience. PMID- 11774624 TI - Expanding living donor options. PMID- 11774625 TI - Disappointing silence. PMID- 11774626 TI - Inaccurate portrayal. PMID- 11774627 TI - Real preventive medicine. PMID- 11774628 TI - Devoted to the heart. PMID- 11774629 TI - [Prospects for the research and clinical work of temporomandibular disorders in China]. PMID- 11774630 TI - [Biomechanical analysis of occlusal splint therapy]. AB - OBJECTIVE: The changes of the location and force of the condyle influenced by occlusal splint were investigated in order to know the biomechanical mechanism of occlusal splint therapy. METHODS: Auto-CAD technology, CT scanning, computer imaging analysis measurement and finite element method were separately used to comparatively analyze condylar position and its stress distribution in patients with temporomandibular joint disorders (TMD) treated with or without occlusal splint. RESULTS: Occlusal splint could lessen anterior space, in crease posterior and upper space in the temporomandibular joint (TMJ), so the condylar position move anterioinferiorly; the stress on condylar surface was lowered, mainly in anterior oblique surface or lateral side of condylar loading position; and the stress symmetry was bilaterally improved. OCCLUSION: The study suggests that regulating condylar position and improving the stress distribution is considered one of biomechanical mechanism of occlusal splint treatment. PMID- 11774631 TI - [An experimental study on the regenerating ability of the condylar cartilage of the rabbit]. AB - OBJECTIVE: To investigate the regenerating ability of the condylar cartilage of the adult rabbit. METHODS: A fullthickness defect was created in the condylar cartilage of the adult rabbit, with or without penetrating into the subchondral bone. RESULTS: In the cases of the condylar cartilage defect without penetration into the subchondral bone, the defects were repaired with fibrous tissue partly. However, in those the defect penetrated the subchondral bone, the defects were repaired with cartilage-like tissue at four and eight weeks periods, then the regenerated tissue transformed into the bone-like tissue. CONCLUSION: The defect of the condylar cartilage can't be repaired with cartilage, and the reparative cells were the undifferentiated mesenchymal cells originated from the bone marrow. PMID- 11774632 TI - [The role of basic fibroblast growth factor on expression of mineralization of periodontal ligament cell population and clones]. AB - OBJECTIVE: To determine the effect of basic fibroblast growth factor (bFGF) on mineraliztion of PDL cell clone. METHODS: The PDL tissue that derived from three human donors was cultured and cells were cloned. The mineralizing ability were detected with or without bFGF treatment in the presence of dexamethasone. Cloned progenitor populations were assayed for their constitutive capacity to bind CAP and express ALP. RESULTS: The results show that bFGF increases clone mineralization (11%), but not in PDL cell population. The cell clones that mineralized only in the presence of bFGF have higher CAP binding ability and lower ALP expression compared with other mineralized clone cells. CONCLUSION: bFGF enhances mineralizing expression of PDL clone. The clones that mineralized only with bFGF treatment are different cell types from the bFGF-undependent mineralized clones. PMID- 11774633 TI - [A study of histopathology and cell proliferation in calcifying odontogenic cyst]. AB - OBJECTIVE: To investigate the histopathologic and clinical characteristics and proliferative activities of calcifying odontogenic cyst (COC). METHODS: 25 cases of COC were reviewed. The expression of proliferating cell nuclear antigen (PCNA) was studied using avidin-biotin peroxidase method and the number of nuclear organizing regions was calculated by means of the argyrophil staining technique in these cases. RESULTS: The cases were divided into 13 (52%) cysts and 12 (48%) neoplasms. Of the 12 neoplasms, 4 were odontogenic ghost cell carcinoma, with a PCNA labelling index (65.9% +/- 7.3%) significantly higher than that of benign neoplastic variant (45.8% +/- 11.5%, P < 0.05) and cystic variant (29.3% +/- 11.2%, P < 0.01). The AgNOR counts was higher in the carcinomatous than benign or cystic variant. CONCLUSION: The lesions show considerable diversity in structure and behavior. It is therefore proposed that quantiation of staining for NOR associated proteins and the PCNA labelling index are diagnostically useful in COC. PMID- 11774634 TI - [A study of epithelial cell kinetics of the odontogenic keratocyst]. AB - OBJECTIVE: To study epithelial cell kinetics of the odontogenic keratocyst. METHODS: Proliferating cell nuclear antigen (PCNA) immunohistochemistry in 60 cases and cellular nuclear DNA contents cytometry in 40 cases were used to compare the epithelial cell kinetics of the odontogenic keratocyst, radicular cyst, dentigerous cyst, and ameloblastoma. RESULTS: The epithelial cells in odontogenic keratocyst has the potential of active growth instead of passive expanding. CONCLUSION: The authors suggest that the odontogenic keratocyst should be termed as "odontogenic keratocystic tumor" because is aggressive growth potential. PMID- 11774635 TI - [Prevalence of subgingival microbiota in Chinese using checkerboard DNA-DNA hybridization]. AB - OBJECTIVE: To evaluate the prevalence of subgingival taxa of periodontal healthy persons and rapidly progressive periodontitis (RPP) patients using checkerboard DNA-DNA hybridization and to find the main pathogens in RPP. METHODS: Eighty four subgingival plaque DNA samples taken from 5 healthy subjects (H) and 6 RPP patients were hybridizated with 37 bacterial probes. RESULTS: The detection frequences of 6 bacteria (E. corrodens, et al.) were greater than 90%. Suspected periodontal pathogens, e.g. A. actinomycetemcomitans seratype b, T. denticola, F. nucleatum as nucleatum, B. forsythus, P. nigrescens, W. succinogenes, C. rectus, P. micros, S. intermedius and P. gingivalis were significantly more frequently found in RPP group than in H group. The mean counts of these pathogens were significantly more elevated in RPP group than in H group. CONCLUSION: It is suggested that periodontal destruction occurrence requires the pathogens in sufficient number at the site, RPP may be resulted from several pathogens. PMID- 11774636 TI - [The effects of the multiple structural layer of Ti-cast on bond of porcelain fused to titanium]. AB - OBJECTIVE: To study the effects of the multiple structural layer of Ti-cast on the bond of porcelain fused to titanium. METHODS: The interfacial state and bond strength of porcelain-titanium were observed by EPM analysis and a shear test. RESULTS: The results showed cracks were observed in the interface of porcelain titanium in R1 (the group of multiple structural layer of Ti-cast), but there were no cracks in the interface of porcelain-titanium in R2 (the group of removed multiple structural layer from Ti-cast) and R3 (the group of wrought titanium). The width of elemental diffusion layer of R1, R2 and R3 were 29.03 microns, 6.90 microns and 7.01 microns respectively. The shear bond srength of R1, R2 and R3 were 29.45 MPa, 52.75 MPa and 48.32 MPa respectively. There were significant difference in the width of elemental diffusion layer and shear bond strength between R1 and R2, R3 (P < 0.01). CONCLUSION: This investigation indicates that the multiple structural layer of Ti-cast should be removed before firing of porcelain. PMID- 11774637 TI - [Effect of guchijianzhou decoction on antioxidation in aged mice]. AB - OBJECTIVE: To observe the antioxidation effect of Guchijianzhou decoction in aged mice. METHODS: The Guchijianzhou decoction was given to aged mice by gastric intubation and compared with a group of young mice and a group of aged mice giving tape water. The LPO, SOD and CAT level were examined. RESULTS: There were significant differences as the experimental group was campared with the control groups. CONCLUSION: The results show that Guchijianzhou decoction is effective in antioxidation and against danage by free radical. It can reinforce antibacterial function and is benificial in the restoration of periodontal health. PMID- 11774638 TI - [Clinical studies on the dental and occlusal conditions of molars with vertical cracking of the root]. AB - OBJECTIVE: To study the contributing factors inducing vertical cracking of the root of molars. METHODS: The dental, periodontal, and occlusal conditions of molars with vertical root cracking were studied in 34 cases (39 teeth). RESULTS: The age range of patients was 40-60 years. The crackings occurred mostly at mesial or mesio-buccal roots, their periodontal conditions were much more worse than those roots without cracking and manifested by deep pocket. The abrasion of the occlusal surfaces was more severe than those molars with no cracking, their contact areas were unstable and deviated buccallly. The direction of force during chewing was therefore horizontal, viz., mesio-distally and bucco-lingually. CONCLUSION: The vertical root cracking of molars is associated with traumatical occlusal contact due to severe abrasion which increases the loading during chewing. PMID- 11774639 TI - [The study on the attrition of molars with occlusal hypersensitivity molars in elderly people]. AB - OBJECTIVE: To investigate the attrition of molars in old people who suffered from occlusal hypersensitivity. METHODS: 113 maxillary and mandibular molars of old people (47-74 years old) who had dentine hypersensitivity caused by attrition were studied. The Lavelle's criteria were used. RESULTS: When the attrition reached to the e type, the rate of lesion rose up quickly (19.47%), the highest incidence was seen in g type (41.59%). The hypersensitivity occurred as 48.67% in the first molar, 51.33% in the second molar, 53.10% in enamel-dentin junction, and 38.05% in dentine concave site. CONCLUSION: The rate of hypersensitivity rises with the severity of attrition. There is no significant difference between the first molar and the second molar, but the incidence of hypersensitivity in enamel-dentin junction is significantly higher than in dentine concave site (P < 0.05). PMID- 11774640 TI - [Investigations on the incidence of dental wedge-shaped defects and abrasion in 501 elderly population and their correlation]. AB - OBJECTIVE: To investigate the incidence of the wedge-shaped defects and abrasion their correlation in elderly. METHODS: 501 elderly were examined. RESULTS: The prevalence of wedge-shaped defects was 89.62% and the abrasion was 100.00%. Both the occurrence rate and abrasive degree were all significantly related with the age and the location of tooth. Patients with severe abrasion had severe wadge shaped defects. CONCLUSION: The wedge-shaped defects and abrasion are common dental diseases in elderly. There would be some common factors in causing both lesions, but the factors that promote the abrasive degree are different. PMID- 11774642 TI - [Occlusion and temporomandibular joint dysfunction syndrome]. PMID- 11774643 TI - [Terminology and diagnostic classification of temporomandibular disorders]. PMID- 11774641 TI - [Biomechanical characteristics of masticatory muscles of rat after using bite plate]. AB - OBJECTIVE: The purpose of this study is to evaluate the changes on biomechanical characteristics of masticatory muscles of rat after using bite plate. METHODS: 30 growing rats were selected to wear the bite plate for four weeks. The changes of contractive force and time of masticatory muscles were measured by method and technique of biomechanics. RESULTS: The biomechanical characteristics of masticatory musclse changed significantly. The contractive tension and contraction time of masseter muscles increased shortened respectively, while that of the digastric muscles increased and prolonged. CONCLUSION: This suggests that the orthopedic mechanism of the bite plate is to alter the original masticatory muscle dynamics and finally to reach the goal of functional jaw orthopedics. PMID- 11774644 TI - [Therapeutic arthroscopy of the temporomandibular joint]. PMID- 11774645 TI - [Study of acidogenesis of dental plaque on cariogenesis using capillary electrophoresis]. AB - OBJECTIVE: The aim was to investigate the relationship of acid production with caries onset. METHODS: Short-chain organic acids of dental plaque from individual subjects were analyzed by capillary electrophoresis. Dental plaques from subjects of caries free and caries active, 21 for each group, were analyzed for 7 short chain organic acids. RESULTS: The in vivo production of lactic acid was a bit higher in caries active-group than in caries free group (but no statistic significance), however, no difference in vitro. CONCLUSION: Therefore, it is hard to relate the net quantity of acid production to the caries onset. PMID- 11774646 TI - [Post diameter optimal design of over dentures attachment]. AB - OBJECTIVE: The effect of the post diameter design of over dentures attachment on the strss distribution of pulpless dentine was investigated in this study. METHODS: The optimal post diameter design was computed with a finite element method and analyzed with graphic method. RESULTS: The changes between the dentine stress value and the post diameter was parabola relationship. The optimal diameter of attachment post was 1.55 mm for this study model. The dentine thickness which retained above apical foramen 4 mm was 0.83 mm. CONCLUSION: This investigation provides a series of valuable parameters for making a post diameter optimal design of over dentures attachment. PMID- 11774647 TI - [Current situation of diagnosis and treatment of salivary gland cancer]. PMID- 11774648 TI - [Arthroscopic sclerotherapy and suturing for disc displacement of the TMJ]. AB - OBJECTIVE: The generation of the scar using TMJ arthroscopic sclerotheray in retrodiscal tissue needs some weeks. As the sclerotherapy can't fix disc reposited at once, we designed some new methods of discal traction suture with posterior sclerotherapy and anterior release. METHODS: 30 cases with 15 joints of disc displacement with reduction and 16 joints of disc displacement without reduction were treated with the above-mentioned techniques. RESULTS: The mean follow-up period was 27 mon (range 6-39). According to the rang of interincisal distances during maximum active opening and painful level using a standard 100 mm visual analog scale, and, analyzing an eight-item jaw pain questionnaire and jaw function using 5 item jaw function questionnaire, the total success rate was 74.2% (23/31), the success rate of disc displacement with reduction was 93.3% (14/15), and the success rate of disc displacement without reduction was 56.4% (9/16). CONCLUSION: TMJ arthroscopic disc traction suture with posterior sclerotherapy and anterior release is effective on disc displacement. Diagnosis, treatment and post-operative evaluation can be performed in the same arthroscopic procedure. PMID- 11774649 TI - [Evaluation in the relationship of disc displacement of temporomandibular joint to osteoarthrosis in the rabbit]. AB - OBJECTIVE: The purpose of this study, using an animal model, was to evaluate the relationship between disc displacement of temporomandibular joint (TMJ) and osteoarthrosis. METHODS: The disc was surgically displaced anteriorly in the right TMJ in each of 25 rabbits. The TMJs were removed after 1, 2, 4, 8, and 12 weeks and stained with H&E. RESULTS: 11 joints had partial anterior disc displacement, 8 joints with complete anterior disc displacement and 6 joints with perforation. The partial anterior disc displacement joints showed early degenerative or physiologic remodeling changes, the complete anterior disc displacement and perforation joints showed degenerative or severe osteoarthritic changes. CONCLUSION: The degree of anterior disc displacement of TMJ relates to the osteoarthrosis. The farther anteriorly, the more easily disc displacement can cause the osteoarthrosis. PMID- 11774650 TI - [A macroscopic and microscopic study of the relationship between the superior lateral pterygoid muscle and the disc of the temporomandibular joint]. AB - OBJECTIVE: To find out the relationship between the superior lateral pterygoid muscle (SLP) and the disc of the temporomandibular joint. METHODS: The cadavers consisted of 47 TMJ specimens from old humans, were used for the macroscopic and microscopic study. RESULTS: (1) The SLP may insert to the disc, the capsule, the anterior discal attachment of TMJ and to the condyle; (2) On average, 52% of the SLP fibres insert to the condyle, 10% to the articular disc, 24% to the capsule and 14% to the anterior attachment of the disc; (3) There is no association between displacement of disc and the proportion of the SLP insert to the disc; (4) The SLP fibres are jointed into the disc fibres by node or tendon, or jointed and to end. CONCLUSION: The majority of the SLP inserts to the condyle and the contraction of the little part of the SLP, which insert to the disc, should not result in the anterior displacement of the disc. PMID- 11774651 TI - [Studies on developmental enamel defects in the primary dentition of children with histories of low birth weight and prematurity and their susceptibility to dental caries]. AB - OBJECTIVE: From the clinical and experimental aspects, to study the susceptibility of dental enamel defects to dental caries in the primary dentition. METHODS: One hundred and seventy-six children (aged 3-8) with histories of low birth weight and premature birth were studied about the relationship of dental enamel defect to caries. Four exfoliated hypoplastic anterior deciduous teeth were studied about the solubility of dental enamel in order to compare the solubility of the defective enamel with that of the normal enamel in the same teeth. RESULTS: The prevalence of both enamel opacity and enamel hypoplasia was significantly interrelated to prevalence of dental caries in those particular teeth. The solubility of the hypoplastic enamel powder was higher than that of the normal enamel in the same teeth. It took shorter time for the hypoplastic enamel powder to attain an equilibrium than the normal did. CONCLUSION: The defective enamel was much easier attacked by caries. PMID- 11774652 TI - [A study on the clinical curative effect by acupuncture for myofascial pain dysfunction syndrome]. AB - OBJECTIVE: To study the acupuncture treatment for myofascial pain dysfunction (MPD) using infrared thermography and microcirculation. METHODS: The temperature of the skin on the TMJ regions, the blood vessels and the blood flow of the Nail Fold capillary loops, were observed in the group of the acupuncture He Gu and Min Yin point and the control group. RESULTS: There were high temperature of the skin on the TMJ regions, and enlarged blood vessels and increased blood flow of the Nail Fold capillary loops in the treatment group, with elimination of, pain and increase of mouth opening as compared with the control group. The effective rate of the acupuncture treatment of 477 cases of MPD is 93.1%. CONCLUSION: The He Gu and Min Yin points are sensitive point for the treatment of MPD. PMID- 11774653 TI - [Electrophoresis of proteins in gingival crevicular fluid of patients with adult periodontitis before and after treatment]. AB - OBJECTIVE: To analyze the overall gingival crevicular fluid (GCF) protein profiles from adult periodontitis (AP) both before and one month after conventional periodontal treatment in expectation to find reliable specific protein markers in GCF for healthy and disease. METHODS: GCF samples were collected using filter paper strips from 56 sites of 12 AP patients. The proteins of GCF were examined via sodium dodecyle sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by the Image Master Electrophoresis Evaluation System. RESULTS: After periodontal treatment, the mean number of protein bands and the abundance and percentage of non-serum derived low molecular weight proteins (12,000, 10,000) decreased significantly (P < 0.001 and < 0.05 respectively). The percentage of non-serum derived 38,000 protein increased and correlated negatively with pocket depth and the volume of GCF before treatment. CONCLUSION: 1. the elevation of the 12,000 and 10,000 proteins are associated with the periodontal inflammation; 2. the elevation of 38,000 protein is associated with recovery. PMID- 11774654 TI - [Subclinical Sjogren's syndrome]. AB - OBJECTIVE: To investigate various manifestations and treatment of subclinical Sjogren's syndrome (SS). METHODS: A long term clinical, laboratory and sialographic observations were performed in 24 patients with subclinical SS. Injectin of thymosin intramusularly was used to treat the patients and clinical effect of this treatment was evaluated. RESULTS: All of 24 cases had experienced recurrent parotid swellings (RPS) for 2-17 years (mean 7 years) before dry mouth and dry eyes occurred and all of them were misdiagnosed as chronic suppurative parotitis or sialadenitis. Follow-up showed that all of these patients developed SS. Vasculitis was found in 8 cases, purpura in 2 cases. The vascular involvement was relatively common in subclinical SS. Main sialographic findings was sialectasis of terminal ducts with irregular dilation of main duct. Frequency of RPS was markedly decreased in the patients treated with thymosin. CONCLUSION: The proposal of subclinical SS has theoretical value for understanding the entity and reclassification of chronic suppurative parotitis, and has guide value for diagnosis and treatment of SS in the early stage. Injection of thymosin is considered an effective therapy to reduce RPS in subclinical SS. PMID- 11774655 TI - [Clinicopathological and diagnostic study of amyloidosis of oral maxillofacial area]. AB - OBJECTIVE: To study the clinicopathological features of amyloidosis studied in oral maxillofacial area and the diagnostic methods. METHODS: HE staining and staining of alkaline Congo red, Immunohistochemical staining, Sections examined by transmitted and polarized light microscopy, Transmitted electron microscopy. RESULTS: 14 cases of the disease were reported. Clinically, the patients usually had progressive enlargement and solidness of the tongue (macroglossia, 12 cases), hard nodules or cords of the cheek and lip mucosa (8 cases), single or multiple hard masses of submandibular and submental areas (6 cases), and ecchymosis or petechiae of the face, neck, chest or oral mucosa. Microscopically, the disease is characterized by the even pink amyloid protein deposit in the soft tissues and the wall of blood vessles, which shows positive staining of alkaline Congo red, Immunohistochemical staining can differentiate the primary amyloidosis from secondary one. Ultrastructurally, Amyloid protein appeares as felt-like finely filament. CONCLUSION: Amyloidosis involving in oral maxillofacial area mainly arise in tongue, less frequently, in buccal and lip mucosa, salivary glands. It is not difficulty to dignosis the disease by HE staining combining with staining of alkaline Congo red and other specific staining methods. Ultrastructural and immunohistochemical study is helpful to make show the dignosis. PMID- 11774656 TI - [A study on the characteristics of articulation for functional speech problem after cleft palate surgery]. AB - OBJECTIVE: To analyze the characterisctics of articulatory errors for the patients with speech problem and whose anatomic or physiologic defect such as velopharyngeal insufficiency were not indicated after cleft palate surgery. METHODS: Fifty patients with functional speech problem outlined above were tested using articulation test in chinese. The frequency of articulatory errors of all consonants was calculated. The interrelativity of the rate of affricates and plosives errors was analyzed. RESULTS: The frequency of affricates (j. z. ch. zh. et al) errors was higher than plosive's (b.d.g.k. et al). The difference of the rate of affricates and plosives errors was significant, statiscally (P < 0.001). CONCLUSION: It is suggested that the frequency of affricates errors was principal in this type of patients. They will be cured by speech training. PMID- 11774657 TI - [Recovery of submandibular gland function following transoral sialolithectomy]. AB - OBJECTIVE: Investigate the recovery of the submandibular gland function following transoral sialolithectomy. METHODS: The glandular function of 26 patients who received the transoral sialolithectomy were investigated by sequential scintigraphy with 99m Tc pertechetate. RESULTS: Most glandular function recovers normal in short time after operation. Glandular infection, calculus diameter and patients's age could influence the recovery of function. CONCLUSION: In the treatment of sialolithiasis, breaking up the pathogenic process of calculus formation and effectively controlling the glandular infection are very important in preventing from the function reduction. After transoral sialolithectomy preserving the anatomical normal orifice of the duct, and using silivators may be very favorable for the function recovery. PMID- 11774658 TI - [Basaloid squamous cell carcinoma: clinical pathological and immunohistochemical study]. AB - OBJECTIVE: To investigate the clinicopathological and immunohistochemical characteristics of basaloid squamous cell carcinoma of oral cavity. METHODS: Routine HE staining and immunohistochemical staining. RESULTS: Basaloid squamous cell carcinoma accounted for 1% of oral squamous cell carcinoma and was more common in male. It could be found at anysite of oral mucosa. The tumor was composed of basaloid cells and squamous cells. Basaloid cell, the main tumor cell, arranged in sheets and nests. Mitosis and comedoform necrosis was often seen. Adjacent oral epithelium often exhibited dysplasia. The tumor cells were cytokeratin positive, S-100 negative; PCNA index was high; 50% cases were p53 positive. CONCLUSION: Oral basaloid squamous cell carcinoma was a higher grade malignant tumor as compared with usual squamous cell carcinoma and should be paid great attention both in treatment and in pathological diagnosis. PMID- 11774659 TI - [Effect of bovine plasma fibronectin on rat papilla cells in vitro]. AB - OBJECTIVE: To observe the effect of exogenous fibronectin (FN) on the rat dental papilla tissues and cells. METHODS: Tooth germs of first mandibular molars obtained from 17-day-old rat (SD) embryos were cultured for 3, 6, 9 days on millipore filters in DMEM supplemented with 10% FCS, 50 mg/L Vitamin c. The dental papilla were isolated by trypsin treatment of homologous tooth germs and cultured on uncoated (control) and FN coated millipore filters for 3, 6 days, bovine plasma FN deposited on millpore filters by treated for 2 hours with 80 mg/L FN. RESULTS: As shown by histological and cytological data, some mesenchymal cells differentiated into odontoblasts and deposited predentine in cultured tooth germs. In cultured dental papillas, polarized functional cells were observed in FN coated group, odontoblast-like cells never differentiated in control cultures. CONCLUSION: FN may be involved in odontoblast polarization. PMID- 11774660 TI - [Histomorphologic study of the bone repair materials by using the cold plasma technique]. AB - OBJECTIVE: The purpose of this article is to improve the biological activity of the implant pretreated by use of cold plasma technic and to investigate the biological effects after implanted into bone. METHODS: First, HA granular was set in the electric field with high voltage and vacuum, then the gaseous mixture of ammonia, hydrogen and nitrogen was led to. By coupled capacity glow discharge, the plasma was produced and the pretreatment was completed. In this way, the surface of HA granular may obtain active amino structure. Sequently, the material was implanted into bone of the animal and the dynamic changes at the material/bone interface were histologically observed. RESULTS: The active group was definitely formed on the surface of the material after pretreatment and there were no adverse effects on the morphology and properties of the base material. Furthermore, the early formation of new bone at the interface of the material/bone was detected, and obvious effects on facilitating bone growth and osseointegration were obtained. CONCLUSION: The findings indicated that cold plasma pretreatment technic was an effective method to improve the biological activity of implant material. PMID- 11774661 TI - [In vivo color measurement of 410 healthy maxillary anterior teeth]. AB - OBJECTIVE: In order to measure and analyse the color characteristics of intra oral vital teeth objectively and accurately. METHODS: The fiber-optic spectrophotometer (FMC-9204, Kunmin, China) was used for measurements of 410 healthy maxillary anterior teeth of 70 people aged from 18 to 70 years old who lived in Kunmin, China. RESULTS: The results were expressed by CIEL*A*B* systems. Statistical analysis showed that: L* of natural teeth is related to age positively, and the regressive equation is L* = 42.74 + 0.14 x age. Value of A* is related to age negatively, the regressive equation is A* = 1.73 - 0.03 x age. The color of the maxillary anterior teeth was also related to tooth position. The central incisor has the highest value of L*, but the canine is the darkest. Besides, the canine is redder, yellower, and more saturated. CONCLUSION: These results may help to make the optic character of oral prosthetic material well matched with the natural teeth. PMID- 11774662 TI - [Evaluation of the treatment effect for bruxism by using myomonitor and occlusal splint]. AB - OBJECTIVE: To evaluate the treatment effect of bruxism by using myomonitor and occlusal splint therapy. METHODS: By using EMG, audiocontrolled recorder and myollectronic recording device to record and analyse the muscles functional state before and after treatment. RESULTS: Splint therapy was more effective than the myomonitor did, such as teeth grinding stopped in 12 cases to 1 case, grinding time decreased in 13 cases to 10 cases and no significant effect in 2 cases to 17 cases. SPD and V/T curve slope of muscles decreased. CONCLUSION: This indicates that the functional state of masticatory muscles got improved. Splint therapy is one of the effective treatment method for bruxism. PMID- 11774664 TI - [Effect of dentin inorganic material during dentin bond]. AB - OBJECTIVE: In order to investigated the effect of dentin inorganic material during dentin bond. METHODS: This study investigated the tensile bond strength (TBS) between 4-META/MMA-TBB resin and dentin treated with several dentin treating methods. RESULTS: When the dentin was treated with acid-salt pretreating solution system (APSS) consisting of 10% citric acid and 3% ferric chloride to remove smear layer, and then re-treated with NaOCl to resolve dentin collagen and reveal dentin inorganic material, TBS of the dentin was 5.93 MPa, and higher than that of control group (3.71 Mpa) (P < 0.05) whose dentin was treated with distilled water only. CONCLUSION: It was suggested that dentin inorganic material did play a proper role in dentin bond. PMID- 11774663 TI - [Three dimensional finite element analysis on the mandibular complete overdenture supported by nature roots or implants]. AB - OBJECTIVE: To investigate the stress distribution around the bone tissue of overdenture supported by teeth roots or implants in the process of mastication which may assist to improve the design of the dentures. METHODS: By means of CT scan, CAD and a three distribution finite element methods to study the stress distribution of the supporting tissue of overdenture supported by roots or implants when various attachment retentive apparatus and various bite forces were applied. RESULTS: No matter overdenture supported by roots or implants the stress distribution on bone tissue are difference between the bar and stud attachments, However these difference were minor compared with the difference caused by the direction of force. The stress value of cortical bone around the roots or implants with twenty degree oblique force is 2.2-3 times higher than that with vertical force. Overdenture supported by implants produced 2.5-4 times higher stress in the cortical bone around than that of overdenture supported by roots when various superstructures or various loads were applied. CONCLUSION: It must consider to reduce the stress peaks and provent bone resorption by increasing the number of implants and using the force-breaking design of implant super-strcture when the overdenture were supported with implants only. PMID- 11774665 TI - [The responses of the microvasculature of the periodontal ligament to horizontal force]. AB - OBJECTIVE: The purpose of this study is to examine the responses of the microvasculature in periodontal ligament(PDL) to horizontal force. METHODS: Using ink injections and celloidin embed, serial sections were cut, then observed by light micrascope, quantitative analysis was conducted by the picture-analysis instrument. Vascular corrosion casts were prepared and examined by scanning electron microscopy. The forth premolars of dogs were pulled by 200 g force in a mesial direction for two hours, and the pressure effects in different positions were demonstrated. RESULTS: The section area of the microvasculature per unit PDL area is obvious larger on the tension sides than on the pressure sides. There is not an obvious distinction on the pressure sides between the experiment groups and control groups. However, there are clear distinctions in the one-third of cervical, and apical segment on the tension sides between the experiment groups and control groups. CONCLUSION: The microvascular changes in PDL had importance to the cushioning effect of PDL when a teeth received a kind of force in a short time. PMID- 11774666 TI - [Insulin-like growth factor 1 regulates collagen synthesis of periodontal ligament cells by a mechanism involving inhibition of poly(ADP-ribose) synthesis]. AB - OBJECTIVE: To investigate the effect of IGF1 on collagen synthesis of PDL cells and the intracellular mechanism of IGF1 action on collagen synthesis. METHODS: Cultured human periodontal ligament cells were used, collagen synthesis, lactate production, PADPR synthesis and PADPR synthetase activity under the action of IGF1 at various concentration for 16 hours were analysed. RESULTS: (1) IGF1 stimulates collagen synthesis of cultured PDL cell. (2) IGF1 increases lactate production of PDL cells, which can be negated by 2-DG. (3) IGF1 decreases PADPR synthesis through inhibiting PADPR synthetase activity of PDL cells. (4) exogenous NAD+ attenuates stimulated collagen synthesis by IGF1 on PDL cells. CONCLUSION: IGF1 stimulates collagen synthesis of PDL cells through inhibiting PADPR synthesis by acting at increasing lactate production which lowers intracellular NAD+ level and at suppressing PADPR synthetase activity. It strongly suggests that PADPR is an intracellular mediator of IGF1 action on collagen synthesis. PMID- 11774667 TI - [An experimental study on the bone repairing ability of recombinant human bone morphogenetic protein-2-coral composited artificial bone]. AB - OBJECTIVE: To improve the bone repairing ability of coral. METHODS: Recombinant human bone morphogenetic protein-2 (rhBMP-2)-coral composited artificial bone was used. The composite was implanted into rabbit calvarial critical-size defects, and coral alone was implanted as control. The rabbits were sacrificed at 2, 6, 12 weeks respectively after operation. The bone repairing ability was assessed by histology and image analysis system. RESULTS: The composite repairing the bone defect both in osteoconductive and osteoinductive manners was seen, repairing ability and effect were better than those of coral. CONCLUSION: The composite is ideal as a bone graft substitute. PMID- 11774668 TI - [Langerhans cell histiocytosis of jaws: a clinical pathological and immunohistochemical study]. AB - OBJECTIVE: To investigate the pathological and immunohistochemical characteristics of chronic localized Langerhans cell histiocytosis (LCH). METHODS: HE staining and histopathological observation, mitotic counting and immunohistochemical staining. RESULTS: 22 cases of LCH were included in this study. The most prominent histologic feature was nuclear polymorphism of Langerhans cells (LC). Nuclear sulcus was often noted. Intercellular spaces were also obvious. Mitotic figures were commonly seen (the mean mitotic index was 7.1 under 10 high magnification fields). The mean PCNA index of LC was 14.5%. Other histiocytes and multinuclear cells were CD68 and cathepsin D positive. CONCLUSION: The nuclear polymorphism of LC is of diagnostic value for LCH, LC in the lesions is hyperplastic and neoplastic in nature rather than simple accumulation and the S-100 positive LC are immature precursors of Langerhans cell. PMID- 11774669 TI - [Ultrastructure of the synovial membrane and the articular cartilage in the temporomandibular joint of the rabbits with occlusal trauma]. AB - OBJECTIVE: To study the effect of occlusal trauma on the ultra structure of rabbits' temporomandibular joints (TMJ) synovial membrane and articular cartilage. METHODS: TMJs from six rabbits with occlusal trauma and three control rabbits were studied by transmission electron microscopy. RESULTS: Degenerative changes of TMJ tissues were found. The articular surface of the condyle was damaged, and the chondrocytes showed signs of degeneration. The synovial lining cell consisted of a number of vimentin intermediate filaments (IFs) which were especially prevalent in the processes as well as paranuclearly. Microvilli on the cell membrane were commonly seen. The vermiform body in the deeper interstitium was also found. Our finding of punctate adherens between synoviocytes was firstly reported in the study. CONCLUSION: The occlusal trauma is really a factor inducing degenerative changes of the TMJ. PMID- 11774670 TI - [Investigation on the positions and relevant factors of wedge-shaped defects in the elderly]. AB - OBJECTIVE: To investigate the position and relevant factors of wedge-shaped defects in elderly. METHODS: 462 elderly were examined. RESULTS: The occurrence rate of wedge-shaped defects was 99.1%, all had at least labial or buccal defects, with premolars the most frequent. However, 15.2% of them had lingual defects, most frequently in molars. No significant association were found between wedge-shaped defect position and tooth brushing or erosion factors in the group. In tooth with defect, the occlusal surface wear was more severe, the denture abutment teeth were more in number, and the functional mobility was increased; in teeth with lingual defect, these phenomena were more obvious. CONCLUSION: The wedgeshaped defects, besides tooth brushing and erosion factors, occlusal force and its accumulation plays a role as well, lingual lesions are more related to traumatic occlusal force. PMID- 11774671 TI - [Inhalation sedation with nitrous oxide in dental extraction]. AB - OBJECTIVE: To study the advantages of nitrous oxide sedation in teeth extraction. METHODS: 112 patients were randomly allocated to four groups: 1) 60 mmol/L nitrous oxide, 2) 60 mmol/L nitrous oxide with estazolam, 3) 40 mmol/L nitrous oxide, 4) 40 mmol/L nitrous oxide with estazolam. The nitrous oxide was used for conscious sedation as an adjunct to local anaesthesia. 53 patients of control group underwent dental extraction with local anaesthesia only. RESULTS: The postoperative MDAS scores of experimental group decreased and was significantly superior to control group (P < 0.01). The patients of experimental group showed a certain levels of sedation and partial amnesia. 97 of the 112 patients (86.62%) preferred inhalation sedation with nitrous oxide. There was no difference between the anxiolytic effects, sedative effects, amnestic effects of the four groups (P > 0.05). Estazolam as preoperative medieation did not show obvious coeffect with nitrous oxide. CONCLUSION: Inhalation sedation with nitrous oxide can provide effects of goodquality antianxiery, sadation, amnesia in dental extraction. PMID- 11774672 TI - [Periodontal regeneration enhanced by BMP and GTR technique]. AB - OBJECTIVE: To evaluate the effects of BMP on the repair of animal periodontal defects by using GTR technique. METHODS: 30 experimental mandibular buccal alveolar periodontal defects were produced surgically around premolar and molar teeth in 8 young mongrel dogs. The exposed root surfaces were curetted to remove the periodontal ligament and the cementum. The defects were devided into 3 equal groups (collagen, collagen + BMP, control). The results were examined histologically 1 month and 3 months respectively. RESULTS: In experimental groups the JE downgrowth was inhibital in the early healing, and the new attachment formation was promoted while comparing with the controls. Compound membrane (with BMP) showed the capacity to support more new bone and cementum formation than the other two groups. CONCLUSION: It is suggested that exogenous BMP can be used in GTR technique to promote periodontal regeneration. PMID- 11774673 TI - [Mandibular compound organs allotransplantion in canines]. AB - OBJECTIVE: To evaluate the feasibility of transplanting composite madibular allogratts to reconstruct large mandibular defects. METHODS: Three composite mandibular transplantation models were designed. The first consisted of hemimandible with the attached teeth, muscles and skin, and oral mucosa. The second was transplanted as the first excluding oral mucosa and some teeth, and the third excluding oral mucosa and all dental crowns. Fourteen transplanting operations were done in canines. Cyclosporine A and methylprednisone were given for immunosuppression. RESULTS: It was confirmed that the composite mandibular organs had an effective and closed return circuit. Transplantation of vascularized mandibular compound organs allografts was feasible. Two longest survivors. 67 and 76 days, were in the third model. Cyclosporine A was successful in suppressing rejection in composite allograft transplant and prolonging survival of transplant models. CONCLUSION: The compoite mandibular allografts had the availability of large bloc of living composite tissues and the good restoration of appearance and function for severe mandibular defects. PMID- 11774674 TI - [The study of normal occlusion's perioral muscle pressure]. AB - OBJECTIVE: To measure the perioral muscle pressure, to realize the relationship between the morphology of dent, occlusion, skeleton and muscle pressure, moreover we established the measuring system and the mini-pressure transducers. METHODS: Thirty volunteers of normal occlusions aging 18.4-20.2 years old were selected. Mini-pressure transducer were bonded on the surface of the tooth. We measured the muscle pressure at rest and during swalling. The collection, handing, statistics of muscle pressure were finished automatically by the computer system. RESULTS: Normal occlusion's muscle pressure is related with sex; there isn't large variation in the intra-individual, but there is great variation in the inter individual; there isn't a force balance between the buccal and lingual sides of the dentition in normal occlusion subjects. CONCLUSION: No matter which kind of occlusion, it has its own stable character of perioral muscle pressure. The buccal and lingual sides force are not equal, the perioral muscle pressure is related with the type of occlusion. PMID- 11774676 TI - [The ultrasonic treatment of curved, fine and obstructed root canal]. AB - OBJECTIVE: To investigate and evaluate the method of managing curved, fine, and obstructed root canals during endodontic treatment. METHODS: Ultrasonic treatment of such root canals was used in 73 cases. RESULTS: The root canals were enlarged and filled in 69 cases, with a success rate of 94.5%. Fracture of the tooth, lateral perforation of the canal, and breaking of the reamer were not found. Failure occurred in 4 cases where the canals were obstructed. CONCLUSION: The ultrasonic treatment of root canal is an effective, practical, and safe method. Nevertheless, its use in curved and severely obstructed root canals is limited. PMID- 11774675 TI - [An epidemiological survey of cleft lip and cleft palate in Fujian province]. AB - OBJECTIVE: To find out the incidence of cleft lip and cleft palate in Fujian provice and to analysis the factors of its deformity. METHODS: From Oct. 1986 to Dec. 1992, the birth defect monitoring was carried out in 22 hospitals in Fujian province. RESULTS: It was found that there were 204 cases of cleft lip (CL) and cleft palate (CP) in 139,882 perinatals. The incidence rate of CL and/or CP was 1.46@1000. Annual incidence rate of CL and/or CP had not found any significant change. CONCLUSION: Among the 204 cases 28 had other deformities. The incidence rate of CL and/or CP related to maternal age, birth order, smoking factors were studied. PMID- 11774677 TI - [Effect of the pH value of acid-salt pretreating solution system on dentin bonding strength]. AB - OBJECTIVE: In order to investigate the mechanism of dentin bond promoted by acid salt pretreating solution system (APSS). METHODS: The tensile bonding strength (TBS) of 4-META/MMA-TBB resin to the dentin, which was treated by acid and retreated by APSS with different pH value, was tested. RESULTS: The TBS of dentin rose gradually from 10.41 MPa to 15.73 MPa with the decreasing of the pH value of APSS. The metallic salt solution containing acid or not, apparently affected the TBS of dentin. CONCLUSION: This study showed that the form of metallic ion in APSS correlated with the TBS of dentin. PMID- 11774678 TI - [SEM and TEM observation on behaviour of invasion of squamous cell carcinoma of the tongue]. AB - OBJECTIVE: To study the invasive behaviour of squamous cell carcinoma of the tongue. METHODS: The cryofracture technique for scanning electron microscope (SEM) and transmission electron microscope (TEM) was used. RESULTS: Cancer cells invaded surrounding tissues by proliferation and penetration en masse, and projected with pseudopodia and lamellipodia. The tensile fibers along and under the cell membrane protruded into the interdigitated filopodia. There were dilatation of intercellular spaces, less number of desmosomes and few gap junctions. All the properties above-described together with increase of cell motility, lytic activity, and decrease of intercellular adhesion were likely to contribute to invasiveness. CONCLUSION: In addition, it was identified that highly dense lymphocytes enclosed cancer nest, which could inhibit invasive action of cancer cells. PMID- 11774679 TI - [Computer aided photocclusion analysis of traumatic occlusion]. AB - OBJECTIVE: This study was designed to analyse traumatic occlusion quantitatively. METHODS: A photocclusion method using computer image processing technique is described, the processing software provide the occlusal contact area, contact point numbers, contact force, maximum stress, and average stress distribution of all teeth by tables and figures. RESULTS: (1) The traumatic contact area was larger and contact force was greater than that of the normal occlusal contact. (2) There was an irregularity force distribution from molars to incisal area. (3) The symmetrical distribution of contact forces and contact areas were destroyed. CONCLUSION: Computer aided-photocclusion method can be used to diagnose traumatic occlusion. PMID- 11774680 TI - [Immunoregulation effect of traditional Chinese medicine treatment on patients with oral lichen planus]. AB - OBJECTIVE: To explore effect of traditional Chinese medicine (TCM) treatment on immune state of patients with oral lichen planus (OLP). METHODS: 30 cases of patients with OLP were treated by TCM and peripheral blood T-lymphocyte subgroup in these patients were determined. RESULTS: CD3, CD4 and CD4/CD3 ratio of patients with OLP were decreased significantly, compared with that of health people (P < 0.01) before TCM treatment, while after TCM treatment CD3, CD4 and CD4/CD3 ratio were increased significantly (P < 0.01) and the latter recovered to normal, 8 patients recovered, 14 cases significantly improved, and 8 cases improved. CONCLUSION: TCM therapy is useful for the treatment of OLP. It acts biphasically a regulation effect on the immunologic balance of the patient. PMID- 11774681 TI - [The orthogonal design study on tumor-inhibition and cancer-block role of Chinese medicinal 1023 co]. AB - OBJECTIVE: To study the effect of Chinese herb medicine on the inhibition of tumor formation and block of malignant transformation. METHODS: The Chinese medicine 1023 co. was given by intubation feeding started simultaneously with the painting of 0.5% DMBA on the hamster's cheek mucosa. RESULTS: The tumor formation in 1023 co. group was delayed for 12 days comparing with the control group and the incidence of dysplasia and cancer in 1023 co. group was lower significantly than that of the control group (P < 0.01). CONCLUSION: The 1023 co. is effective in inhibiting tumor formation and blocking cancerous transformation. By orthogonal design we find the proper prescription is A2 B2 C2 D1. PMID- 11774682 TI - [Accuracy of computerized aid diagnosis, surgical simulation and facial appearance prediction in orthognathic surgery]. AB - OBJECTIVE: The purpose of this report is to evaluated the accuracy and potential advantages of the computer system in orthognathic surgery. METHODS: The accuracy of computer prediction was evaluated in 31 patients by using the orthognathic surgery prediction expert system (OSPES) in the preoperative analysis, diagnosis, surgical simulation and preoperative facial appearance predication. RESULTS: This system could accurately predict the postoperative changing. The prediction accuracy for single-jaw surgery was over 95%; double-jaw 85%. The prediction for hard tissue was more accurate than that for soft tissue. CONCLUSION: The results of this study suggest that computer system is an acceptable tool for facial appearance prediction. PMID- 11774683 TI - [Comparison of sampling methods and their effects on alkaline phosphatase levels in gingival crevicular fluid]. AB - OBJECTIVE: To observe the change of alkaline phosphatase (ALP) after repeat sampling and compare the two sampling methods (orifice method and intra-pocket method). METHODS: Gingival crevicular fluid (GCF) was sampled repeatedly by the interval of 20 minutes, with orifice and intra-pocket method respectively, and the levels of ALP in GCF were determined. RESULTS: Mean levels of ALP per site and concentration of ALP are not statistically different between two samples after repeat sampling with-orifice method as well as intra-pocket method (P > 0.05). ALP levels (per site and per microliter) are much higher for intra-pocket method than orifice method (P < 0.001). From the viewpoint of the numbers of recovery sites after repeat sampling, though ALP levels at most sites can't entirely recover to their original levels with both method, intra-pocket method is still a little better than orifice method, and ALP levels per site is better than ALP concentration. CONCLUSION: The interval of repeat sampling should be prolonged more than 20 minutes. It is better to determine the GCF-ALP with intra pocket method and also the recommended pattern that express enzyme levels is total activity per site but not concentration. PMID- 11774684 TI - [The changes of suppressor T-cells function in patients with RAU]. AB - OBJECTIVE: To study the change of suppressor T-cell function in patients with RAU. METHODS: Samples of 12 patients with RAU active phase were studied by it suppressor assay. RESULTS: The T-cell suppress rates at ConA 1,2,4 and 8 mg/L were 60%, 40%, 27% and 20% respectively, and were evidently lower when compared with normal controls' 72%, 56%, 41% and 34% (P < 0.05). CONCLUSION: The suppressor T-cell function may be depressed in RAU patients. PMID- 11774685 TI - [The radiopaque evaluation of NaI radiopaque resinifying agent in vitro]. AB - OBJECTIVE: To study the possibility of using radiopaque resinifying agent in resinification of the tooth. METHODS: 65 teeth resinified with radiopaque resinifying agent in vitro were evaluated on X-ray films and through stereomicroscope. RESULTS: 86.11% of the root canals on X-ray films was with good contrast, 95.37% of them was with enough radiopaque length. CONCLUSION: The radiopaque length could really indicate the filling length of the radiopaque resinifying agent in the root canals. PMID- 11774687 TI - [The study on treatment of Chinese children's Class II malocclusion by Herbst appliance]. AB - OBJECTIVE: To study the effects of early treatment for chinese children with class II malocclusion. METHODS: 30 chinese children were treated by Herbst appliance. The cephalometric analysis were used to evaluate the effects of early treatment. RESULTS: Herbst appliance can restrict the growth of maxilla and stimulate the growth of mandible, at the same time, the appliance leads to the retroclining of upper incisors, proclining of lower incisors and mesial movement of lower molars. CONCLUSION: Herbst appliance can achieve remarkable effects of growth modification for chinese children's class II malocclusion. PMID- 11774686 TI - [Electrophoretic analysis of protein composition in gingival crevicular fluid]. AB - OBJECTIVE: To seek the protein composition related to periodontal diseases. METHODS: 86 gingival crevicular fluid (GCF) samples were collected by rinsing the sulgingival sulci from subjects with healthy gingiva (20), gingivitis (24) and periodontitis (42). The protein composition were examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) on a Phast System. The gels were scanned and analyzed using Phast Image with computer. RESULTS: In inflammatory condition, the serum derived proteins with MW 82,000, 77,000, 17,000 occurred more frequently than in healthy gingiva, and the occurrence and abundance of non-serum derived proteins with MW 41,000, 21,000, 12,000 were also increased in inflammatory condition compared with healthy gingiva. CONCLUSION: The high levels of proteins with MW 82,000, 41,000, 21,000, 12,000 are close related to the periodontal inflammatory status. PMID- 11774688 TI - [One year observation of craniomandibular structure changes of skeletal Class II patients in early permanent dentition]. AB - OBJECTIVE: To study the craniomandibular growth of skeletal class II patients in early permanent dentition so that demonstrate malocclusion development and decide orthodontic treatment opportunity. METHODS: Forty skeletal class II patients in early permanent dentition were selected at random and observed for one year. The lateral cephalometric X-ray films were taken before and after observation for every patient, then Downs analysis and doublet test were made. RESULTS: Female patients' jaws relation didn't change in early permanent dentition, but upper incisors were more protrusive than before, and lower incisors inclined lingualy. Male patients' mandible grew upward and forward, but the absolute value of small change. CONCLUSION: It is necessary to treat skeletal class II deformities early. PMID- 11774689 TI - [Treatment of deep anterior overbite by using the fixed appliances in conjunction with a small bite plate]. AB - OBJECTIVE: This study was to investigate the effective method in the reduction of deep anterior overbite. METHODS: Twenty-nine cases of three-degree deep anterior overbite were treated by using the fixed appliances in conjunction with a small bite plate. RESULTS: It was showed that this method was significantly quicker to reduce deep overbite of anterior teeth (2.04 +/- 0.78 mm per month) and shorter to require the time of treatment (3.94 +/- 1.55 months) than that by using the single fixed appliances (P < 0.001), and there was no significant difference between the adults and juveniles. These findings suggest that it was effective for both of adult and juvenile patients. CONCLUSION: As the destruction of molar tubes, wire and bracket bonding failure caused by bite were less happened, it was effective to treat complicated cases of deep overbite with a shorter occlusogingival distance, posterior cross-bite and not enough alveolar highness of posterior teeth who could be difficult to treat by a routine method. PMID- 11774690 TI - [The effect of Vit. B12 injection into acupoints in the treatment of verruca plana]. AB - OBJECTIVE: To study the therapeutic effect of combined western and traditional Chinese medicines for the treatment of verruca plana. METHODS: Acupoint injection of Vit. B12 was used to treat 91 patients suffering from verruca plana after unsuccessful therapy of more than 3 methods. RESULTS: Complete cure, 35 cases; significantly improved, 56 patients. The total effective rate was 100%. Compared with the Vit. B12 i.m. injection group and polyinosinic cytidy lic acid i.m. injection group, the difference was highly significant (P < 0.001). The results were also proved by histologic examination. CONCLUSION: The Vit. B12 acupoints injection is a simple and effective method for the treatment of facial verruca plana. PMID- 11774691 TI - [Detection of small alveolar bone lesions by digital subtraction radiography]. AB - OBJECTIVE: To employ digital subtraction radiography (DSR) system developed by our school and co-ordinative unit, for diagnosis of small artificial alveolar bone lesions, in order to evaluate the system. METHODS: Seventy-two 0.2-0.9 mm3 lesions were produced in premolar and molar areas of the dry human mandibles. The reference and subsequent radiographs were taken before and after lesions being made. The small lesions were detected by conventional radiographs and by DSR method respectively. RESULTS: As for 0.2-0.5 mm3 lesions, the detections by both DSR and conventional methods were less than 50%. As for 0.7 mm3 lesions, the detection by DSR and conventional methods were 57.5% and 38.7%, respectively (P < 0.01). As for 0.9 mm3 lesions, the accuracy of the detection by DSR and conventional methods was 89.3% and 57.3% (P < 0.01). CONCLUSION: The detectability of small alveolar bone lesions by DSR system was obviously superior to the conventional method. PMID- 11774692 TI - [Human tongue carcinoma model established in nude mice by orthotopic transplantation and studies on its major biological properties]. AB - OBJECTIVE: To establish clinically relevant animal model of human tongue carcinoma. METHODS: Cell suspensions of human tongue squamous cell carcinoma cell line (Tca8113) were inoculated orthotopically into nude mice and the growing tumors were serially passaged by orthotopic transplantation. The oral cavity, mandible and neck of the nude mice were sectioned and examined histologically. The ultrastructure and chromosome of the tumors were also investigated. RESULTS: 1. The success rate of transplant was 90%. 2. The mouse-growing tumors exhibited the same identical properties as the donor tumor. 3. Human tongue cancer cells could grow in the homologous oral cavity site of nude mice, extended and metastasized to adjacent tissues and lymph node of the neck. CONCLUSION: The model can be useful for evaluating biological behavior and new therapeutics for tongue cancer. PMID- 11774693 TI - [Experimental study of cattle bone grafting in combination with implant insertion]. AB - OBJECTIVE: To study the effect of cattle bone grafting in combination with implant insertion. METHODS: Twenty cattle bone blocks were onlayed on the rabbit tibial metaphysis, which were fixed by dental implants. Triple fluorochromes were sequentially given to animals following the operation. New bone formation was histologically and histomorphometrically evaluated. RESULTS: The fluorochrome labelled new bone gradually replaced almost all the spongy bone and the partial cortical bone of the graft at the end of the experiment. There was a significant higher percentage of bone area at the first four thread levels at 84 days than at 21 days. The average mineral apposition rates ranged from 1.90 microns/d to 2.75 microns/d. CONCLUSION: The onlay cattle bone grafting in conjunction with screw type dental implants can be used to increase the volume of the recipient bone. PMID- 11774694 TI - [Therapeutic arterial embolization of oral and maxillofacial plexiform hemangioma with absolute ethanol and gelfoam particles]. AB - OBJECTIVE: To treat arteriovenous malformations of the oral and maxillofacial region by embolization with absolute ethanol and Gelfoam particles. METHODS: Six patients with arteriovenous malformations of the oral and maxillofacial region were treated by selective embolization through the feeding arteries with absolute ethanol and Gelfoam particles. RESULTS: A follow up at 2-13.5 months after embolization showed no recurrence. Response rate is 100 percent. CONCLUSION: Alcohol and Gelfoam as an agent used to ablate high-flow vascular malformations in oral and maxillofacial region is a method of choice. PMID- 11774695 TI - [Electronic speckle pattern interferometric analysis on force distribution of different mandibular unilateral free-end dentures]. AB - OBJECTIVE: To study the force distribution of three kinds of mandibular unilateral free-end partial denture under vertical loading on the artificial tooth. METHODS: A fresh mandible with right 2nd and 3rd molars missing was restored with cantilever fixed partial denture (CFD), casting three arm clasp removable partial denture (CCD) and RPI removable partial denture (RPID) respectively. The force distribution on the surface of supporting bone was studied by using electronic speckle pattern interferometry (ESPI). The ESIP was displayed real-time and recorded. The fringes determining was prossed by microcomputer image processing. The corresponding out of plane displacement of the supporting bone was measured and analyzed. RESULTS: Showed all of the three kinds of dentures contribute to transmit stress to supporting bone. The corresponding out of plane displacement of supporting bone decreased, the degree of decrease was CFD < CCD < RPID in order. CONCLUSION: This finding provides a useful reference for design of denture construction. PMID- 11774696 TI - [Studies on the causative factors of cervical wedge-shaped defect of human teeth from three dimensions]. AB - OBJECTIVE: To investigate causative factors of cervical wedge-shaped defect of human teeth and the significance of methods for measurement of the defect. METHODS: Experimental cervical defects on 9 pairs of premolars were created by cross-brushing, erosion, or fatigue of occlusion force separately or combinedly and measured in depth and area of profile as well as in volume. RESULTS: 1. Profile depth of defects caused by three factors separately showed no statistical difference, but the profile depth caused by combining factors was much more than that caused by each individual factor; 2. The hardness of enamel and dentin in defect area was lower than that in normal area of tooth samples; 3. Measurement from one-dimension (depth) and two-dimension (area) showed only low relation in profile depth, however, measured three-dimensionally (volume) there existed moderate relationship. CONCLUSION: For study of cervical defect, the profile depth is feasible provided that is a large sample group and without equipment for volume measuring; if the sample size is limited and there is sophiscated instrument for volume measuring, the 3-dimensional measurement is the most sensitive one. PMID- 11774697 TI - [Diagnostic imaging of adhesions of the temporomandibular joint]. AB - OBJECTIVE: To study the image diagnostic criteria of adhesions of the TMJ. METHODS: 26 cases of intra-articular adhesions were collected from 103 cases with internal derangement of TMJ. The clinical examination, arthrographic findings and arthroscopic detections were compared. RESULTS AND CONCLUSION: The arthrographic findings showed that the lack, interruption and irregular joint margins of contrast material appeared in the superior space, the posterior band of disc appeared in the same relative position in both the closed and open views and intra-articular adhesion often associated with anterior disc displacement. PMID- 11774698 TI - [Effects of overextended mouth opening on substance P-like immunologic reaction of TMJ soft tissues]. AB - OBJECTIVE: To probe deeply into the traumatic characteristics and the neurobiologic mechanism of overextended mouth opening of the temporomandibular joint (TMJ). METHODS: Changes of the substance P-like immunologic reaction (SPIR) of the TMJ soft tissues were examined with ABC immunohistochemical staining along with the histopathological study of the overextended opening. RESULTS: An obvious increase of SPIR brought about by overextended opening was mainly in the anterior extending tissue of the disc, the bilaminar zone and the subsynovial layer of the articular capsule, and the extent of the reaction became greater with the increased duration of over-opening. The SPIR decreased obviously two weeks after removing the nocuous stimulation. The changes of SPIR almost coincided with the histopathological changes in sites and extents, and in the effects on them of the relevant treatment, which indicate that there are some internal relations between the two kinds of changes. CONCLUSION: To recognize the characteristics of the changes and grasp the internal relations will help us to find new approaches to the prevention, diagnosis and treatment for the trauma and pain of the TMJ. PMID- 11774699 TI - [Three dimensional reconstruction of human permanent teeth]. AB - OBJECTIVE: Dental anatomy is one of the most important basic courses in the education of stomatology. The deep understanding of morphologic characters is closely instructive to the clinic of endodontics, oral surgery, orthodontics and prosthodontics. METHODS: In present study, 32 permanent teeth from a skull specimen were inputted into computer after the processes of burying, grinding, photographing, scanning and recognizing. By the techniques of reconstruction, the 3D stereo tooth models were retrieved from 2D digital data. RESULTS: On the basis of those 3D data, computer graphics techniques were used to realize the lighted, smoothed and shaded teeth. CONCLUSION: Such a series of data teeth might be applicated as a corner stone of the computer aided instruction (CAI) in stomatology. PMID- 11774700 TI - [Vascular structure of malignant tumours of the mandible shown by specimen arteriography]. AB - OBJECTIVE: To investigate the vascular structure of different kinds of malignant tumours of the mandible. METHODS: Specimen arteriography was performed on 11 cases of malignant tumours of the mandible. RESULTS: Malignant tumours could be divided into two groups: 1. the hypervascular tumours, the arteries are dilated, distributed evenly and arranged in a bush-like pattern. 2. hypovascular tumours, the scanty arteries are distributed unevenly without dilation, in some areas, the shape of arteries are irregular and arranged in a network pattern. CONCLUSION: Variation in vascular structure of malignant tumours in the mandible may be related to the outcome of regional chemotherapy. PMID- 11774701 TI - [Differences in intake of food and nutrients between manual and desk workers]. AB - AIM: To compare intake of food and nutrients between manual and desk workers. SUBJECTS AND METHODS: Subjects were 28,603 residents (13,432 were male and 15,171 were female) in a city. Using a questionnaire, information on frequencies of consumption of different foodstuffs for one year and the type of employment was collected. Intake of nutrients was calculated from the frequencies and compared between manual and desk workers. The comparison was carried out with stratification by gender and adjustment for age and smoking habits. RESULTS: Desk workers took larger amounts of protein and lipids, and smaller amounts of carbohydrates than manual workers. Predominant foodstuffs in the latter was rice wheat products, potatoes and soybean products, while desk workers consumed more meat, processed meat, milk products, fish, vegetables and fruits. CONCLUSIONS: Differences in intake of nutrients and food depending on occupation should be considered, when the relationship between health status and employment is evaluated. PMID- 11774702 TI - [Prevalence of disabilities of the upper and lower extremities among community dwelling middle-aged and elderly women]. AB - OBJECTIVE: In order to obtain baseline data for designing programs aimed at promoting physical function among elderly people in Japan, we determined the prevalence of disabilities affecting upper and lower extremities and their impact on function in community-dwelling middle-aged and elderly Japanese women. METHODS: Subjects were 580 women aged 40 years and over, living in Oshima town, Nagasaki, Japan. Information on disabilities affecting all four extremities was collected by questionnaire. Subjects were asked about the extent of disability in each extremity (no disability, some, moderate, cannot or very difficult to use extremity) and the reason for the disability. The functional level was defined using a disability score, calculated by summing the disabilities for upper or lower extremities (no disability, 0; some, 1; moderate, 2; cannot or very difficult to use, 3). Women who scored 0 were classified as 'good', women who scored 1-2 'fair', and who scored 3-6 as 'poor'. RESULTS: Prevalence of disability affecting the upper extremities increased significantly with age (11.9% with some or greater, and 4.3% with moderate or worse). Disabilities of the lower extremities also increased significantly with age (27.2% with some or greater, and 12.9% with moderate or worse), affecting a larger proportion of individuals. With regard to the upper extremities, the women classified a 'fair' and 'poor' increased significantly with age (9.5% with 'fair', and 2.4% with 'poor'), and function decreased (p = 0.003). The same was the case for the lower extremities (19.0% with 'fair', and 8.3% with 'poor') (P < 0.001). The most frequently cited cause of disability was arthritis, both in the upper (20%) and lower (40%) extremities, followed by stroke (10%), fracture (10%) and trauma not associated with fracture (10%). CONCLUSIONS: In middle aged and elderly women, disabilities of the upper and lower extremities become more prevalent and are associated with further functional impairment with aging. Such disabilities are more common in the lower extremities, and arthritis seems to be the most frequent cause. PMID- 11774704 TI - [An epidemiological study on Shigella sonnei outbreak associated with contaminated drinking water--Nagasaki, Japan, May 1998]. PMID- 11774703 TI - [Study on the effects of walking on functional fitness in aged patients with the hand-arm vibration syndrome]. AB - PURPOSE: This article reports the effectiveness of mild walking exercise for maintaining functional fitness in aged patients with the hand-arm vibration syndrome (HAVS). SUBJECTS AND METHODS: Fifty-two patients suffering from vibration syndrome, for which they received annual compulsory examination from December 1998 to March 1999 at the San-in Rosai Hospital, were examined. They all were male, with a mean age (standard deviation) of 69.1 (7.3) years, and were randomly allocated to an intervention group (N = 26) and a control group (N = 26). The goal of the intervention was to achieve and maintain at least 30 minutes of walking a day. Functional fitness was assessed by a sitting and standing test, a zigzag walking test, a hand working test with a pegboard for dexterity, and a self-care working test proposed by the Physical Fitness Research Institute, Meiji Life Foundation of Health and Welfare. RESULTS: There were no significant differences between the two groups regarding baseline characteristics. The proportions of subjects with regular exercise habits after the intervention were 84.6% (22/26) and 53.8% (14/26) in the intervention and control groups, respectively, the difference being significant. The total scores for functional fitness were improved in the intervention, while decline was noted in the control group. Sitting and standing and self-care working ability were also improved in the intervention group as against the deterioration with age in the control group. CONCLUSIONS: Our findings show to some extent that intervention using mild exercise, walking for 30 min, is effective for aged patients with HAVS to maintain and improve functional fitness. PMID- 11774705 TI - [A study on contamination from Legionella spp. at a home for the elderly in Toyohashi City]. AB - OBJECTIVE: Legionnaires disease has been attributed to Legionella spp. in the water distribution systems of buildings. However, recently cases due to contamination of thermal-bath water have been reported in Japan. In this investigation, we examined the supervision of baths and the presence of Legionella spp. in thermal-bath water of homes for the elderly in Toyohashi city. METHODS: The research was conducted through questionnaires on bathing facilities at 50 sites. Thermal baths were found to be installed at 14 of the sites. We then tested 22 samples from the 14 sites for Legionella spp. and other materials. RESULTS: From the genus Legionella, only Legionella pneumophila was detected, in 8 samples from 4 sites. Coliforms were also detected. Moreover, disinfectant was not detected in any of the Legionella positive samples of bath water. Legionella positive sites had, however, been replacing their water once a day. CONCLUSIONS: These findings indicate that the use of disinfectant and the proper supervision of bathing facilities are important in controlling Legionella spp. Legionnaires disease can be averted in homes for the elderly through appropriate measures. PMID- 11774706 TI - Inclusion body myositis associated with hepatitis C virus infection. AB - Inclusion body myositis (IBM) is a chronic progressive inflammatory myopathy in elders. Three patients with chronic hepatitis C developed IBM. Their muscle biopsies were examined by polymerase chain reaction (PCR) for two patients and immunohistochemistry for three patients. The hepatitis C virus (HCV)-RNA genome was detected in one of the two patients. The degenerated and atrophic muscle fibers were immunoreactive for an anti-HCV antibody in all three patients. Immunoreactivity for an anti-HCV antibody was not apparent in the muscle specimen from an IBM patient without HCV infection. Our findings suggest that HCV infection is related to the pathogenesis in some cases of IBM. PMID- 11774707 TI - [Excitatory effect of noradrenaline on rat airway parasympathetic ganglion neurons]. AB - The effects of noradrenaline (NAd) on neurons acutely isolated from airway parasympathetic ganglia of rats were investigated by use of the nystatin perforaded-patch recording mode. Under current-clamp conditions, an application of 10(-6) M NAd onto the ganglion neurons evoked a depolarization which was accompanied by regenerating repetitive action potentials. NAd concentration dependently induced inward current with decreasing membrane conductance when a ganglion neuron was held at a holding potential of -40 mV. The half-maximum effective concentration (EC50) of NAd was 1.7 x 10(-7) M, and the response was mimicked by an alpha 1-adrenoceptor agonist cirazoline and was inhibited by WB 4101, an alpha 1A-adrenoceptor antagonist. Oxymetazoline, a partial agonist for an alpha 1A-adrenoceptor, also evoked the inward current with an EC50 of 3.5 x 10(-8) M. The maximum current induced by oxymetazoline (10(-6) M) was 44% of that induced by NAd. NAd also inhibited the amplitude of M-current deactivation induced by hyperpolarizing step from a VH of -25 mV to -50 mV with an EC50 of 2.0 x 10(-4) M. These results suggest that NAd directly depolarizes the airway parasympathetic ganglion neurons of rats associated with an inhibition of M current through the alpha 1A-adrenoceptors. PMID- 11774708 TI - [Progress in Alzheimer research]. PMID- 11774709 TI - [The molecular mechanism of aging and longevity and the function of Sir2 proteins]. PMID- 11774710 TI - [Functional disorders of the esophagus in the elderly]. PMID- 11774711 TI - [Difficulties in diagnosis and treatment of asthma in the elderly]. AB - The cause of the high asthma mortality in the elderly is not exactly known. We measured intrabronchial pressures in elderly asthma patients who had long standing asthma and compared them with those in newly-diagnosed asthma and young healthy volunteers. In elderly asthmatics, at baseline conditions, both central and peripheral airway resistances were significantly higher compared with those in the other groups, which may partly explain the high asthma mortality in the elderly. We report a case of severe acute asthma associated with disturbed consciousness, in which asthma-induced cerebral swelling was considered to be accompanied by neuronal damage, after examination of cerebrospinal fluid. Inhaled steroid is essential for the treatment of moderate to severe asthma. However, approximately 40% of the elderly patients in this category did not use inhaled steroid. Physicians should strongly recommend the use of inhaled steroid to prevent asthma death in elderly asthma patients. PMID- 11774712 TI - [Predictors for functional capacity in older people]. PMID- 11774713 TI - [The role of cholesterol in the pathogenesis of Alzheimer's disease]. PMID- 11774714 TI - [Allogeneic hematopoietic stem cell transplantation for older adults (mini transplantation)]. AB - Allogeneic hematopoietic stem cell transplantation after conditioning regimen with high dose cytostatic drugs and total body irradiation may induce severe transplantation related complications especially in older adults. Recently, several reports showed successful engraftment in older patients with hematological and non hematological malignancies after reduced doses of cytostatic drugs. So called mini-transplantation (nonmyeloablative hematopoietic stem cell transplantation) might be able to induce graft-versus-leukemia/tumor effect (GVL/T) without severe transplantation related complications. Older patients and patients with reduced performance status induced by prior infectious and organ complications might benefit from this mini-transplantation strategy. PMID- 11774715 TI - [DHEA, osteoporosis, nuclear receptor and aging]. PMID- 11774716 TI - [Approach to the elderly with urinary incontinence]. PMID- 11774717 TI - [The role of oxidative stress in ageing]. PMID- 11774718 TI - [Molecular genetic analysis of Werner syndrome]. PMID- 11774719 TI - [Analysis of causative genes and genetic risk factor in Alzheimer's disease]. AB - Recently, some Alzheimer-associated genes have been found: amyloid beta protein precursor (APP), apolipoprotein E (apoE), presenilin 1 (PS-1), and presenilin 2 (PS-2). First, we failed to discover other susceptibility genes of familial Alzheimer's disease (FAD). However, we disClosed a novel mutation. Asp678Asn (D678N), in the APP gene in a pedigree of early-onset Japanese FAD. The alteration in the aggregation properties of mutant A beta may be involved in the pathogenesis of FAD with D678N APP mutation. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheimer's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphism of the ER alpha gene may be a genetic risk factor for SAD. PMID- 11774720 TI - [Transcriptional regulation of the presenilin-1 gene by cAMP-response element binding protein]. PMID- 11774721 TI - [Role of steroid receptors in osteoporosis]. PMID- 11774722 TI - [The prevention of pneumonia in the elderly by dopamine agonists]. PMID- 11774723 TI - [The effects of pulmonary rehabilitation with chronic obstructive pulmonary disease (COPD)]. AB - It is controversial whether pulmonary rehabilitation is effective in patients with chronic obstructive pulmonary disease (COPD). To test the effect of pulmonary rehabilitation, 7 patients with COPD (aged 76.0 +/- 2.6 years) were enrolled in pulmonary rehabilitation program for 6 weeks. The program consisted of relaxation, pursed lip breathing, diaphragmatic breathing, panic control, muscle stretch gymnastics, and exercise training. The distance of the 6-minute walking test increased significantly from 246.4 +/- 38.0 (m) to 304.3 +/- 28.4 (m) (p < 0.05). The minimum SpO2 during the 6-minute walking test increased from 86.0 +/- 2.8 (%) to 90.1 +/- 1.3 (%) and dyspnea as measured with Borg scale decreased from 5.6 +/- 1.1 to 4.6 +/- 0.5, although they were not significantly different. These results suggest that pulmonary rehabilitation might improve exercise tolerance in elderly patients with COPD. PMID- 11774724 TI - [Relationship between depression and lipid metabolism in the elderly with hypertension]. AB - In order to examine the relationship between depressive symptoms and the lipid metabolism in the elderly with hypertension, we recruited 311 outpatients aged 65 or older with hypertension and defined depression as patients with 6 or more symptoms on Geriatric Depression Scale short form. We further classified depressed patients into three groups: mild depressed with 6-7 symptoms, moderate depressed with 8-10 symptoms and severe depressed with 11 or more symptoms. Serum total cholesterol, serum HDL cholesterol and serum LDL cholesterol levels were significantly higher in female depressed patients than those in nondepressed patients (TC, 194.6 +/- 30.1 vs 208.0 +/- 32.8 p < 0.01; HDL, 67.3 +/- 19.3 vs 72.3 +/- 16.2 p < 0.01; LDL, 107.6 +/- 26.5 vs 116.0 +/- 29.1 p < 0.05). In male patients, serum lipids were not significantly associated with depressive symptoms but depressed patients were significantly older than nondepressed patients (75.3 +/- 6.2 vs 78.0 +/- 5.9 p < 0.05). Concerning the analysis of the severity of depression, serum total cholesterol and serum LDL cholesterol levels were significantly higher in mildly depressed patients than nondepressed patients in females and the same tendency was seen in male patients. No linear associations were shown between the severity of depression and serum lipids. We concluded that hyperlipidemia may be associated with depressive symptoms in elder patients with hypertension and that it might be related the severity of depression. We need to further investigate the relationship between depression and lipid metabolism in larger population samples. PMID- 11774725 TI - [Clinical features of elderly patients with hepatocellular carcinoma]. AB - To clarify the clinical features and to select optimal treatment of hepatocellular carcinoma (HCC) in the elderly, 163 patients were divided into the following three groups and retrospectively evaluated: Group O (> or = 70 years of age, 47 cases), Group IM (< 70 and > or = 60 years, 70 cases) and Group Y (< 60 years, 46 cases). There were fewer HBsAg-positive cases and those in clinical stage III in Group O than in Group Y (p < 0.05). Although the percentage of women and small HCCs in Group O were somewhat higher than those in other groups, there were no significant differences among the three groups with regard to sex, size of nodule and time after blood transfusion. Most of the alcohol-abuser were in Group Y (p < 0.05). Some active treatment was possible in 76.6% of the elderly individuals, in 87.1% of the patients of Group IM, and in 78.3% of the Group Y, while few underwent hepatic resections (Group O, 4.3% vs. Group IM, 8.5% vs. Group Y, 8.6%) or PMCT (4.3% vs. 11.4% vs. 8.6%). The allocation of other therapeutic modalities in the three groups were also statistically identical. The prevalence of concomitant diseases was significantly higher in the elderly patients (53%) than in their younger counterparts (Group IM; 30%, Group Y; 28.2%) (p < 0.05). Although the reasons for the paucity of treatment in Group IM and Y (9 and 10 cases) were liver-associated factors (i.e., advanced clinical stage or tumor size), attempts to apply therapeutic measures were abandoned in 11 cases in Group O because of their advanced age (2 cases) or heart failure (1 case). The 5 year survival rate was higher in Group O (55%) than those in Group IM (32%) and Y (26%) (p < 0.01). These results suggest that because of the higher incidence of concomitant diseases, less invasive therapeutic modalities, such as PEI/PMCT, should be recommended for elderly patients with HCC. PMID- 11774726 TI - [Can sleep urine calcium concentration corrected by osmolality as a screening test identify subjects with risk to develop osteoporosis?]. AB - The reliability of overnight (sleep) urine (SU) and 2nd morning urine (2MU) were compared with that of 24-hour urine (24 U) for the evaluation of bone resorption markers. A total of 50 women were subjected to the study was were divided into two groups according to their lumbar bone mineral density, namely 25 females with normal BMD (mean age 47) and 25 women with low BMD (mean age 78). Calcium (Ca), collagen degradation products crosslaps (CTx), pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) were measured in 24 U, SU and 2MU and corrected for urine volume with creatinine (Cr) and osmolality(Osm). Among these four components, the corrected values tended to be higher in SU than 2MU, regardless of the method of correction and BMD level. Ca, CTx, Pyr and D-Pyr concentrations in spot urine were always significantly correlated with total excretion/body weight (Kg) regardless of the method of correction and BMD level. In low BMD subjects, Ca, CTx and D-Pyr concentrations corrected by Osm with further correction by body weight as an index of body size in the SU were significantly correlated with BMD. The SU may be a sensitive indicator of augmented nighttime bone resorption replacing 24 U especially on correction by Osm to eliminate the influence of sodium intake as an extraskeletal factor. In 51 women with normal BMD (A) with a mean age of 56, 16 with osteopenia (B) with a mean age of 64 and 35 with osteoporosis (C) with a mean age of 71, correlation coefficients were calculated between lumbar BMD and Ca/Osm, Ca/Osm/Kg, Ca/Cr and Ca/Cr/Kg in SU. Although no significant difference of mean urine Ca values were found between A and B groups, Ca values in C were significantly higher than that of A regardless of the correction method. The mean value of Ca/Osm/Kg in C was significantly higher than that of B. Ca/Osm/Kg showed a significant negative correlation with BMD in C. On examination of the correlation between % change of BMD in 23 women with a mean age of 59 and Ca concentration in SU corrected by urine volume and body weight, Ca/Osm was -0.427 (p = 0.0419), Ca/Osm/Kg -0.450 (p = 0.0313), Ca/Cr -0.400 (p = 0.058) and Ca/Cr/Kg -0.420 (p = 0.0462), suggesting the usefulness of Ca/Osm/Kg as an indicator of low BMD in screening. PMID- 11774727 TI - [The relationship between fall-related activity restriction and functional fitness in elderly women]. AB - The purpose of this study was to assess the relationship between experiences of falls or fear of falling and functional fitness in the elderly. A total of 41 women, aged 66-88, who visited Fall Prevention Clinic in Tokyo Metropolitan Geriatric Hospital, underwent an interview and functional assessment. We used a questionnaire about falls, fear of falling, activity restriction, and twelve variables were used to assess functional fitness. Data were collected from June 2000 to November 2001. The subjects were classified into four subgroups: the faller group (n = 29) were subjects who had at least one or more experiences of falling accidents in the past one year; the non-faller group (n = 12) were subjects who did not have any falling accidents in the past one year; the activity restricted group (n = 12) were subjects who were restricted from going out because of fear of falling; the activity non-restricted group (n = 23) consisted of subjects who did not have any restriction concerning going out because of fear of falling. The results were: 1) Among all subjects, 85.4% had fear of falling. Among the subjects who had fear of falling. 34.3% had restricted outdoor activities due to the fear of falling. 2) Where 86.2% of the faller group responded that they had fear of falling. 83.3% of the non-faller group also responded as having fear of falling. Of the faller group, 44.0% had some restriction concerning going out because of fear of falling. In the non-faller group, 10.0% of them showed some restriction concerning going out because of fear of falling. The rate of activity restriction in the faller group was significantly higher (p < 0.05) than in the non-faller group. 3) The faller group had significantly reduced LNG with eyes open and closed, one-leg balance with eyes open, tandem walking, grip strength, and leg extension than the non-faller group. 4) The activity-restricted group exhibited significantly reduced one-leg balance with eyes open, Up & Go test, grip strength, and leg extension than the activity non-restricted group. In conclusion, lower leg strength and walking ability as well as history of falls are significant predictors of activity restriction in elderly women related to fear of falling. PMID- 11774728 TI - [Intravenous pamidronate delivery to a case with multiple bone metastasis of breast cancer]. AB - MRI and bone scintigraphy of a 64-year-old woman admitted with severe lumbago showed multiple metastatic bone cancer mainly on vertebrae, and breast cancer was found by mammography. After enucleation was performed, treatment with tegafur, tamoxifen and oral bisphosphonate/etidronate was started. Because symptoms associated with bone metastasis worsened, we began to administer 30 mg of pamidronate intravenously every 4 weeks. Since that time the extent of metastasis has been inhibited, resulting in ameliorated lumbodynia and improved quality of life. PMID- 11774729 TI - [Early treatment with non-invasive positive pressure ventilation a successful case of bulbar type amyotrophic lateral sclerosis]. AB - A 60-year-old man who has suffered dysarthria since 1999. He had noticed twitching of right upper extremity and orbicularis oris muscle since August 2000. The bulbar type of amyotrophic lateral sclerosis was diagnosed. He was admitted for evaluation of sleep disorder with respiratory distress on November 20, 2000. Arterial blood gas analysis on admission showed marked hypercapnea (PaCO2:51.6 Torr). Nocturnal hypoxia index, which was calculated using the nocturnal oximetry monitoring, was elevated. Non-invasive positive pressure ventilation started during sleep at night, although it was earlier than to start for mechanical ventilation. After one week, both hypercapnea and his nocturnal hypoxia index, together with symptoms, improved markedly. Respiratory insufficiency due to progressive fatigue of respiratory muscles, such as diaphragm and intercostal muscles, is a major cause of death in amyotrophic lateral sclerosis. In general mechanical ventilation is introduced when marked hypercapnea and dyspnea become clinically overt. However, the exact time to introduce noninvasive methods of ventilatory support for amyotrophic lateral sclerosis has not been established. Based on the observation in this patient, we would suggest that earlier introduction of non-invasive mechanical support for ventilation (nocturnal hypoxia index > 70) would be useful to improve the symptoms and to prolong the life of patients with ALS. The nocturnal hypoxia index is useful to decide the time of the introduction of non-invasive mechanical support for ventilation. PMID- 11774730 TI - [An autopsied case of marked cardiac hypertrophy due to multifactorial heart disease in an 85 year-old man who had been socially active]. AB - An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease. PMID- 11774731 TI - [Malignant syndrome caused by a combination of bromperidol and donepezil hydrochloride in a patient with probable dementia with Lewy bodies]. AB - The patient was a 68-year-old man with a 1-year history of delusions related to well-formed and detailed visual hallucinations. Bromperidol 12 mg was prescribed to treat his symptoms. After a diagnosis of dementia of Alzheimer's type was suspected, the patient received donepezil hydrochloride 5 mg. One week later, the patient's Parkinsonism deteriorated. One month later, the patient developed radical edema of the eyelids and the anterior neck, hypoproteinemia, and severe anteflexion of the body. One and a half months later, the patient developed malignant syndrome. His medication was discontinued and parenteral nutrition was started. The patient recovered from his malignant syndrome. However, 1 month later, his Parkinsonism had not improved. The patient received levodopa to treat his Parkinsonism and his symptoms subsequently improved. The hallucinations and systematized delusions returned. The patient's cognitive impairment deteriorated on one side. The aggravation of extrapyramidal symptoms and the development of malignant syndrome were believed to have been caused by the combination of bromperidol and donepezil hydrochloride and poor nutrition. Caution should be exercised when prescribing an antipsychotic drugs with donepezil hydrochloride. PMID- 11774732 TI - [Non-operative management of dens fracture in an elderly patient with severe complications]. AB - An 82-year-old woman was diagnosed with hypertension at the age of 50 and had been treated with antihypertensive agents. Proteinuria was detected at age 60 and her renal function subsequently deteriorated. Hemodialysis was started on February 14, 2000. She fell out of the bed and hit her neck in the early morning on February 15. Neck X-ray tomography revealed Anderson type III dens fracture. Since she had several complicating conditions including angina pectoris and arrhythmia, she was treated by external fixation using a halo-vest. The neck pain improved gradually. During her clinical course, she experienced delirium due to immobilization. However, bone union was complete 5 months later. Physicians should be aware of the possibility that even minor injury can cause dens fracture in elderly patients. Conservative management of type III dense fracture should be considered for elderly patients with a compromised condition. PMID- 11774733 TI - [Analyses of factors influencing prognoses of elderly patients who receive visiting nurse service]. PMID- 11774734 TI - [Health-related quality of life assessed by EuroQol in home care patients with stroke]. PMID- 11774735 TI - [Current advances and expectations in tumor immunology]. AB - Natural killer (NK) cells and Interferon (IFN)-gamma have been implicated in immune surveillance against tumor. We demonstrated the critical role of perforin in NK cell-mediated cytotoxic activity and anti-tumor effect in IFN-gamma inducible IL-12. And, we recently reported that TRAIL is constitutively expressed on a substantial proportion of murine NK cells in the liver, and which is responsible for spontaneous cytotoxicity and the anti-metastatic activity against TRAIL-sensitive tumor cells along with perforin and Fas ligand. Interestingly, the TRAIL expression on liver NK cells appeared to be regulated by endogenously produced IFN-gamma. Consisting with this finding, IL-12 and NKT cell specific ligand, alpha-Galactosylceramide (alpha-GalCer), induced TRAIL-mediated cytotoxcity and anti-tumor effect, and which was mediated by TRAIL expressed on IFN-gamma-activated NK cells. Tumor necrosis factor(TNF)-related apoptosis inducing ligand (TRAIL) is a type II transmembrane protein belonging to the TNF family, which preferentially induces apoptotic cell death in various tumor cells in vitro. Preclinical studies in mice and nonhuman primates have shown that administration of recombinant soluble forms of TRAIL could suppress the growth of TRAIL-sensitive tumor xenografts with no apparent systemic toxicity. These studies suggested a potential utility of TRAIL as a cancer therapeutic, although TRAIL expression at protein levels and its physiological roles in tumor surveillance has remained unknown. Presented findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor. PMID- 11774736 TI - p53 gene status and chemosensitivity in ovarian cancer. AB - Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene. PMID- 11774737 TI - Novel approaches to reversing anti-cancer drug resistance using gene-specific therapeutics. AB - One of the underlying mechanisms of multidrug resistance (MDR) is cellular overproduction of P-glycoprotein (P-gp), which acts as an efflux pump for various anti-cancer drugs. P-gp is encoded by a group of related genes termed MDR; only MDR1 is known to confer the drug resistance, and its overexpression in cancer cells has been a therapeutic target to circumvent the resistance. To overcome P gp-mediated drug resistance, we have developed six anti-MDR1 hammerhead ribozymes and delivered them to P-gp-overproducing human leukemia cell line by a retroviral vector containing RNA polymerase III promoter. These ribozyme-transduced cells became vincristine-sensitive, concomitant with the decreases in MDR1 expression, P-gp amount and efflux pump function. Among the ribozymes tested, the anti-MDR1 ribozyme against the translation-initiation site exhibited the highest efficacy. The retrovirus-mediated transfer of this most potent anti-MDR1 ribozyme into a human lymphoma cell line, which was made resistant by infection of pHaMDR1/A retroviral vector and thus possessed a low degree of MDR due to P-gp expression relevant to clinical MDR, resulted in a complete reversal of MDR phenotype. In addition to retrovirus-mediated transfer of ribozymes, we evaluated the efficacy of cationic liposome-mediated transfer of ribozyme. Treatment of a P-gp-producing human breast cancer cell line with the liposome-ribozyme complex resulted in reversal of resistance, concomitant with the decreases in both MDR1 expression and P-gp amount. Confocal microscopic imaging of the cells after treatment with liposome/FITC-dextran showed cytoplasmic fluorescence that was abolished by cytochalasin B, indicating a high endocytotic activity in these cells. The endocytotic activity was well correlated with the success of cationic liposome mediated transfer of MDR1 ribozyme. These distinct approaches using either retrovirus- or liposome-mediated transfer of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR cells with different properties such as endocytotic activity as a specific means to reverse resistance. PMID- 11774738 TI - Antifolate resistance and its circumvention by new analogues. AB - We have established human leukemia cell lines made resistant to various antifolate drugs and analyzed resistance mechanisms developed in these cells at the cellular and molecular levels. The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Each resistance mechanism was not necessarily induced at random, but appeared to relate to the biochemical and pharmacological properties of the drug exposed, biological dispositions of the cells, drug-exposure manners to, or culture conditions of the cells. Since it has been shown that a minor modification at the specified position of the folate structure resulted in a drastic change in its pharmacological properties, many new compounds have been rationally designed on the basis of the knowledge of relationships between structure modifications and pharmacological properties. The step-by-step approach to the development of new analogues led to the discoveries of several promising antifolate drugs such as trimetrexate and raltitrexed, which can overcome the acquired and natural resistance to methotrexate, a classical antifolate, and clinical trials of these newer classes of antifolate compounds are currently underway. PMID- 11774739 TI - Mitochondria in platinum resistant cells. AB - Based on the previous report showing that mitochondrial (MT) alteration is associated with platinum (Pt) resistance, we have determined how the alternative MT function is involved in Pt cell cytotoxicity particularly in relation to the apoptosis. MT membrane potential (delta psi m) semi-quantitatively assessed by rhodamin 123 (Rh) sensitivity was significantly elevated in acquired Pt-resistant 2008/C13*5.25 cells (C13) established from its parental 2008 cells or known intrinsic Pt-resistant JHOC cells established from ovarian clear cell adenocarcinoma. Laser confocal microscopy of these cells stained with Rh revealed that MT in Pt-resistant cells were distributed in whole cytoplasm with relatively higher fluorescent intensity whereas MT in Pt-sensitive cells were localized in perinuclear space with lower fluorescent intensity. Electron microscopy showed the predominantly condensed MT in which crestal structure was not observed clearly in Pt-resistant cells. Western blot analysis using murine monoclonal anti Bcl-2 antibody showed more than 5-fold Bcl-2 overexpression in Pt-resistant cells in response to cisplatin treatment. Cytochrome C (CytC) in MT was released from MT into cytoplasm in response to cisplatin treatment in Pt-sensitive cells, whereas up-regulation of CytC level in MT rather than CytC release from MT was observed in Pt-resistant cells. These data are strongly suggesting that changes at MT level would impact on the relative resistance of malignant cells to undergo drug-induced apoptosis. PMID- 11774740 TI - Apoptosis and anticancer drug resistance. AB - Anticancer agents induce cancer cell death through apoptosis or necrosis. As anticancer agents at low and high concentrations cause apoptosis and necrosis, respectively, cancer cells may be merely injured by an anticancer agent in apoptosis, and cell death may result from an activation of the internal constituents to induce apoptosis. Therefore, an alternation of apoptotic pathway must change the efficacy of anticancer agents. As an escape of cancer cells from apoptosis seems to be closely associated with the development of anticancer resistance, this report focuses on mechanisms of apoptosis and its association with anticancer resistance. A Bax induces apoptosis mitochondria-dependently, whereas Fas can induce apoptosis mitochondria-independently. An interaction of Bax and Bcl-2 is very important to decide cell life or death, and Bcl-2 phosphorylation may control this interaction: Paclitaxel treatment induced Bcl-2 phosphorylation and typical apoptosis, whereas hyperthermia induced not Bcl-2 phosphorylation but nuclear translocation and failed to induce apoptosis. Moreover, Fas was localized in the cytoplasm of exponentially growing cells and on the cell membrane of confluent cells. We would like to emphasize that it is very important to check the localization of constituents of apoptosis in order to evaluate the susceptibility of cancer cells to apoptosis. PMID- 11774742 TI - Suppression of urokinase expression and tumor metastasis by bikunin overexpression [mini-review]. AB - Bikunin (bik, also known as urinary trypsin inhibitor [UTI]), a Kunitz-type protease inhibitor, interacts with cells as a negative modulator of the invasive cells. Human ovarian cancer cell line, HRA, was treated with phorbol ester (PMA) in order to evaluate the effect on expression of urokinase-type plasminogen activator (uPA). Preincubation of the cells with bik reduced the ability of PMA to trigger the uPA expression at the gene level and at the protein level. We next asked whether the mechanism of inhibition of uPA expression by bik is due to interference with MAP kinase, since PMA could also activate a signaling pathway involving MEK/ERK/c-Jun-dependent uPA expression. When cells were preincubated with bik, we could detect suppression of phosphorylation of these proteins, demonstrating that bik markedly suppresses the cell motility possibly through negative regulation of MEK/ERK/c-Jun-dependent mechanisms, and that these changes in behavior are correlated with a coordinated down-regulation of uPA which is likely to contribute to the cell invasion processes. To clarify the role of bik on tumor metastasis, HRA cells were transfected with an expression vector harboring a cDNA encoding for human bik. Transfection of HRA with the bik cDNA resulted in five variants stably expressing functional bik and significantly reduced invasion, but not proliferation, adhesion, or migration relative to the parental cells. Animals with bik* transfectants induced reduced peritoneal dissemination and long term survival. These results suggest that transfection with the bik gene induces the suppression of tumor cell invasion and peritoneal dissemination, and can prolong survival. This pre-clinical animal model offers the possibility to explore gene therapy as a new treatment modality for ovarian cancer. PMID- 11774741 TI - Hammerhead ribozymes to modulate telomerase activity of endometrial carcinoma cells. AB - Telomerase is an excellent target molecule for cancer therapy, though any effective agents have never been developed in human subjects. We designed a variety of hammerhead ribozymes against human telomerase RNA (hTR) and hTERT mRNA and studied their possibility as a tool for cancer therapy. To search promising target site of hTR, the catalytic actiuity of 3 kinds of hammerhead ribozymes was studied in cell-free system. They showed equivalent catalytic activity, but only 36-ribozyme, which was designed to cleave the template region of hTR, revealed telomerase inhibitory activity in an endometrial carcinoma cell line. Among hTERT mRNA-targeted ribozymes, the ribozyme to cleave 13 nucleotides downstream from the 5'-end of hTERT mRNA (13-ribozyme) exhibited the strongest telomerase inhibitory activity, and the ribozyme to cleave 59 nucleotides upstream from the poly(A) tail showed clear activity. Stable transfection studies confirmed that the 36-ribozyme as well as the 13-ribozyme suppressed telomerase. These observations suggest that the template region of hTR and 5'end of hTERT mRNA are promising target sites for ribozymes to reduce telomerase activity. PMID- 11774743 TI - The role of topoisomerase I inhibitor in cisplatin-resistant ovarian cancer. AB - We discussed the role of DNA topoisomerase I (topo I) inhibitor, which is now widely used in clinical practice, in cisplatin-resistant ovarian cancer. Our study showed the synergistic actions between cisplatin and 7-ethyl-10 hydroxycamptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-pyperidino) 1-piperidino]carbonyloxycamptothecin (CPT-11), in two cisplatin-resistant cancer cell lines, HeLa/CDDP and KFr cells, but not in each parent cell line, HeLa and KF cells. Furthermore, HeLa/CDDP cells had a collateral sensitivity to SN-38. The levels of topo I protein in the cisplatin-resistant cells did not differ from those of their parent cell lines and were unaffected by exposure to cisplatin. In contrast, topo I enzymatic activity was 2-4 fold higher in the cisplatin resistant cell lines compared with their respective parent cell lines. A significant correlation between the sensitivity for SN-38 and topo I activity human clear cell carcinoma cell lines, which are known as intrinsically ciasplatin-resistant cancer, was observed. Next, we examined the relationship between topo I activity and sensitivity to second-line chemotherapy consisting of cisplatin and CPT-11. A total of 30 patients with ovarian cancer who had initially undergone chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide (CAP) and exhibited measurable lesions were entered in the study. Tumor samples were obtained in the period between the initial and the second-line chemotherapy. Of those 30 patients, 18 responded to second-line chemotherapy and 12 did not. Topo I activity in tumor samples of responder was significantly greater than that of in nonresponders. In 8 cases whose samples could be obtained before and after CAP, topo I activity significantly increased after CAP therapy. Consequently, the combination therapy with cisplatin and CPT 11 may be effective for patients with cisplatin-resistant ovarian cancer. In addition, topo I enzymatic activity may be a predictor of the sensitivity for topo I inhibitor. PMID- 11774744 TI - Prevention of mycoplasma contamination in leukemia-lymphoma cell lines. AB - The contamination of cell lines with mycoplasmas is certainly one of the major problems occurring in cultured cells. Analyzing more than 460 human leukemia lymphoma (LL) cell lines, we found that 28% of the cultures were mycoplasma positive. Mycoplasmas can produce extensive changes, growth arrest and cell death in the infected cultures. While mycoplasma-infected cell lines can be truly cleansed from the contaminants, all the efforts would be in vain when the cells return to a mycoplasma-infested environment or are handled with unsuitable culture practices. Hence, the main focus of mycoplasma control should be on preventing cell culture contamination. Mycoplasmas can be introduced through several routes including culture reagents and laboratory personnel. Cross contamination from infected cell cultures within one laboratory continues to be the major source for the spread of mycoplasma. Specific technical protocols and cell culturing guidelines may be followed in order to minimize the risk of mycoplasma contamination of cell lines. This "good culture practice" is of utmost importance as faulty cell culture techniques appear to be also the main reason for the high incidence of cross-contaminated LL cell lines which according to our experience using DNA fingerprinting of some 500 LL cell lines is about 15%. PMID- 11774745 TI - Nuclear localization of bovine immunoglobulin G (bIgG) in the liver of rats injected with hydrocortisone-bIgG conjugate intravenously. AB - Bovine serum albumin conjugated with steroid hormone injected intravenously into rats can enter the hormone-target cell nuclei with its antigenicity kept intact (Nishimura and Nakano, 2000). Antinuclear antibodies (ANA) such as immunoglobulin G (IgG) are found in some autoimmune diseases. To confirm immunocytochemically whether immunoglobulin G (IgG) conjugated with steroid hormone enters in the hormone-target cell nuclei, bovine IgG (bIgG) was conjugated with hydrocortisone 21-hemisuccinate. The hydrocortisone-bIgG conjugate was injected into the vascular system of adrenalectomized rats. Then the rats were killed 2 or 3 h after injection to detect bovine IgG in the hormone-target cell nuclei of the liver by fluorescein-isothiocyanate labeled-anti bovine IgG antibody under confocal laser scanning microscopy. In the liver of both rats injected with hydrocortisone-bIgG, the fluorescence was observed in not only the cytoplasm but also the nuclei of liver cells. In control rat injected with bIgG, few nuclei showed fluorescence. These results demonstrate that bovine IgG conjugated with steroid hormone can enter the hormone-target cell nuclei of rat with its antigenicity kept intact, and suggest that antinuclear antibody in some autoimmune diseases may be transported from blood plasma into the nucleus. PMID- 11774746 TI - Development of the human gracilis nucleus: a morphometric evaluation. AB - The development of the human gracilis nucleus was studied on serial sections of the brain of 9 fetuses and neonates at 18-40 weeks of gestation, a two-month-old infant and a 63-year-old adult using a microscope with a drawing tube and an image-analyzing computer system. A morphometric evaluation revealed that the human gracilis nucleus, whose neurons were distinguished from glia from 18 weeks of gestation onward, showed a gradual development in terms of the columnar volume, neuronal size and number, and revealed two kinds of phenomenon: a normal process which occur in the development of the fetus, viz. natural cell death (also called apoptosis), and a phenomenon due to yet unknown causes regarding a discrepancy between the number of neurons and the neuropil index. PMID- 11774747 TI - SEM study on the dorsal lingual surface of the lesser dog-faced fruit bat, Cynopterus brachyotis. AB - The dorsal lingual surface of the lesser dog-faced fruit bat was examined by scanning electron microscopy (SEM). Filiform (Fi), fungiform (Fu) and vallate papillae (V) were observed. The Fi papillae were distributed over the entire dorsal surface of the tongue. The Fi papillae notably differed in morphology by their location on the tongue and could be classified into 5 types: 1) crown-like papillae, 2) giant trifid papillae, 3) scale-like papillae, 4) small conical papillae, and 5) large conical papillae. The Fu papillae were present rounded bodies on the anterior 2/3 of the tongue. The lesser dog-faced fruit bat showed the triangular arrangement of the three V, with the apex of the triangle directed posteriorly. PMID- 11774748 TI - N-linked oligosaccharides predominantly distribute in rat cerebellar cortex. AB - The distribution or localization of glycoconjugates in rat cerebellar cortex was investigated with 26 different kinds of lectins observed by light and electron microscopy. In paraffin-embedded tissues, PHA-L, PHA-E, DSA, WGA, ConA, LEA, LCA, PSA, and RCA-I, which mainly recognize N-linked oligosaccharide sugar structures, stained the cerebellar cortex, especially the molecular layer. PHA-L staining showed the highest selectivity for the molecular layer among these lectins. Pretreatment with N-glycanase altered the staining intensities of these lectins, whereas pretreatment with O-glycanase did not alter the intensity. In electron microscopy, the cell membrane and Golgi membranes of Purkinje cell, parallel fibers, and synaptic vesicles exhibited a positive reaction with PHA-L. Nuclear pores and synaptic vesicles were positive for WGA binding. These results suggest that there exist N-glycoside binding oligosaccharides predominantly in the cerebellar cortex, especially in the molecular layer, which sugar chains may be relevant to the synaptic transmission in the molecular layer. PMID- 11774749 TI - The mandibular nerve in edentulous jaw humans: analysis of myelinated nerve fibers. AB - We studied the nerve fibers of the human mandibular nerve using edentulous jaw cadavers. We made nitrocellulose sections and stained them with Goto's modification of Masson-Goldner's method in order to evaluate the nerve fibers using an image-analyzer. The results showed an unusual feature: a sudden increase of axonal areas during the decade of the 80s followed by a sharp return to previous levels after that age, even though the number of nerve fibers kept decreasing with the aging process. Although the reason for this is not yet understood, the authors consider that it might be due to compensatory phenomena. PMID- 11774750 TI - The morphology of the iridocorneal angle in the eye of buffaloes (Bos bubalis): a light and scanning electron microscopic study. AB - The morphology of the iridocorneal angle in the eye of the buffalo (Bos bubalis) was studied in eighteen eyes using light and scanning electron microscope (SEM). The buffalo iridocorneal angle included the pectinate ligament, the ciliary cleft, the trabecular meshwork (uveal and corneoscleral) and the angular aqueous plexus. The pectinate ligament was prominent anteriorly and appeared as strong, thick compact structure. The strands of the pectinate ligament were short and had narrow spaces between them as observed by SEM. The ciliary cleft appeared quadrilateral and contained large amount of trabecular tissue that could be divided into two parts, the uveal part and the corneoscleral part. The uveal meshwork was the internal part of the trabecular meshwork. It occupied wide area in the anterior region and narrow area in the posterior one. It composed of thick pigmented trabeculae in the anterior part, which became thin and loose in the posterior part. Their intertrabecular spaces were large and wide anteriorly. The corneoscleral meshwork was the external part of the trabecular meshwork. It was narrow anteriorly and widened posteriorly. Their trabeculae were non-pigmented and closely arranged and the intertrabecular spaces were small. The angular aqueous plexus consisted of four to five veins. They were located between the outer border of the corneoscleral meshwork and the inner border of the sclera. These results of the iridocorneal angle suggest important implications for understanding the glaucoma disease in buffaloes. PMID- 11774751 TI - Planning a meeting. AB - Meetings are a necessary, but manipulatable, aspect of doing business and getting things done. But they are work. Giving preparatory thought about a meeting's style and content, whether you are the planner or the attendee, can achieve great results. PMID- 11774752 TI - Treating corneal trauma. PMID- 11774753 TI - Bioterrorism. PMID- 11774754 TI - Conscious sedation of children in A&E. PMID- 11774756 TI - Trauma course content after the Gulf War. PMID- 11774758 TI - Turning the tables. Violent or abusive patients can now be banned from NHS treatment. PMID- 11774759 TI - The challenge for emergency nurses is to believe in their profession and in themselves. PMID- 11774760 TI - [Percutaneous nephrostomy in emergencies. Report of 42 cases]. AB - PURPOSE: Through this work we are going to demonstrate the interest and the contribution of the percutaneous nephrostomy in obstructive anuria and in pyonephrosis. PATIENTS AND METHODS: It is a retrospective study concerning 42 cases. The average age of the patients is 50 years (19-80 years). The sex-ratio is 26 men for 16 women. The nephrostomy was realized in first intention or after failure of ascent stent on 33 patients for an obstructive anuria and nine patients for a pyonephrosis. RESULTS: Improvement of the renal function was noted in 100% of obstructive with anuria and apyrexy in every case of pyonephrosis. No major complication arose during the realization of the nephrostomy. The long-term prognostic depends on the etiology. CONCLUSION: The percutaneous nephrostomy constitutes a saving, effective and temporary solution in the strategy of the coverage of obstructive anuria and pyonephrosis. PMID- 11774761 TI - [Diffuse xanthogranulomatous pyelonephritis: clinical, anatomopathologic, and therapeutic features. Report ot 9 cases and review of the literature]. AB - Diffuse xanthogranulomatous pyelonephritis is a rare chronic pyelonephritis. This study permitted us to notice the various histological, clinical, radiological, and the different means diagnoses of this affection. Retrospectively series of nine patients is reported. The median age was 43 years. The commonest clinical presentation was urinary tract infection, and lumbar pain. Urine culture identified a bacteria in seven cases (77%). Intravenous urography recovers silent kidney (five cases), hydronephrosis (two cases), chronic pyelonephritis (one case) and renal stones in six cases (67%). Treatment consisted of nephrectomy. No specific biological or radiological signs of this affection can be identifying this lesion in preoperative. The diagnosis was revealed by the histological examination of the removed kidney. The outcome is favorable after a follow-up of six months to four years. The clinical features of the pyelonephritis xanthogranulomatous is not specific. Magnetic resonance imaging can give a specificity to this affection. Only histological examination is able to established the definitive diagnosis. PMID- 11774762 TI - [Percutaneous nephrolithotomy. Report of 211 cases]. AB - The case files of 198 patients with a stone, treated by percutaneous nephrolithotomy between 1985 and 1999, were studied. This series consisted of 113 men and 85 women with a mean age of 41 years (17-71 years). The stone was in the pelvis (167 cases) of the kidney, multiple in 40 cases and staghorn in four cases. The complications were septic in six cases and hemorrhagic in five cases. The overall stone-free rate at three months was 92%. PMID- 11774763 TI - [Spontaneous perirenal hematomas. Report of 3 cases]. AB - Spontaneous retroperitoneal hemorrhage is an uncommon affection, the diagnosis was recognized by sonography and CT scan, but the etiology remains unknown and exploration for diagnosis may become necessary. In the absence of an apparent etiology, patients with spontaneous renal bleeding should undergo radical nephrectomy, because of the extremely high incidence of small undetectable occult tumors. Three further cases were reported by the authors, who made a review of the literature. PMID- 11774764 TI - [Bilateral adrenal pheochromocytomas in von Hippel-Lindau disease]. AB - The pheochromocytoma is a medullo-adrenal tumor which develops at the cost of the chromaffin cells. It appears in 11-19% of cases of von Hippel-Lindau's disease (VHL), is often bilateral, and the symptomatology is often crude: arterial hypertension is frequently isolated and unstable, and the classic triad of headache, palpitations and sweating is quite rarely observed. We report four observations of bilateral pheochromocytomas in patients with von Hippel-Lindau's disease (three with phenotype IIA and one with phenotype IIB). The tumor was bilateral during the diagnosis in three cases; in the fourth patient, the attack on the contralateral adrenal gland came two years after the first adrenalectomy. All the patients had undergone an adrenalectomy by open surgery after a short preparation of 48 hours; replacement therapy was begun in each patient. Morbidity was low, and the patients submitted to a prolonged follow-up in order to screen for the onset of future lesions of VHL. PMID- 11774765 TI - [Treatment of primary pyogenic abscess of the psoas: retrospective study of 18 cases]. AB - The primitive abcess of psoas muscle is a rare affection which involves mainly the young. The authors report 18 cases of primitive pyogenic abcess of psoas collected during a period of six years in the urology service of UHC Ibn Rochd Casablanca. The purpose of this review is to discuss the different therapeutic attitudes. The study concerned 11 men and seven women, their mean age was 35 years. The mean delay of evolution was 45 days. The physical exam found a psoitisis (five cases) and a flunk swelling (14 cases). The ultrasound exam showed the collection which was hypoechogenic in seven cases and heterogenous in 11 cases. The CT scan showed an heterogenouse hypodense collection without enhansment in seven cases. The use of antibiotherapy alone (four cases) and percutaneous drainage (four cases) permitted the recovery just respectively in one and two cases. Fifteen patients (83%) were operated through a postero-lateral lumbotomy route without costal resection. The bacteriological exam of the pus found a Staphylococcis aureus (ten cases) and Escherichia coli (two cases). The evolution was favorable in 14 cases; one patient was dead at fifth day post operatively by heart infarction. For the authors, the surgical drainage remains the treatment of choice. PMID- 11774766 TI - [Recanalization of pelvic ureter in prostatic neoplastic obstruction: endoscopic and radiologic approach]. AB - Obstruction of the lower ureter by pelvic cancer requires a palliative treatment. Percutaneous derivation is often performed as an emergency. If obstruction is limited to the peri-meatic area (a few mm or a cm) resection of the ureteral orifice can be enough to catheterize the obstructed ureter. Stenting of the ureter can be done even if the obstruction is longer, using the extra vesical repermeabilization. METHODS: A guide wire is passed via the nephrostomy, and ureteral stent is passed over the guide wire. Dye additionned with methylene blue is injected tovisualize the lower extremity of the ureter. A regular resectoscope is placed transuretraly, and resection is conducted using X ray localisation with a C arm and several incidences. The tissue resected first is usually extravesical, in the adipous perivesical tissue. Dissection of this area can be performed bluntly with the tip of the resectoscope until the ureter is reached. At this time, the resectoscope is used to open the lower extremity of the ureter, localized with the C arm. It is important to open widely the ureter, so as to be sure to catheterize easily this opening with a ureteral catheter. A double J can then be passed easily. Tunnel of several cm can be performed using this technique. RESULTS: Seven patients with pelvic cancer with obstruction of the last cm of the pelvic ureter were included in this series. They were recurrent prostate cancer already treated with hormone therapy, stage T3, T4. All procedures were performed under rachianesthesia or general anesthesia according to general status. After this procedure normal miction were obtain in all patients and nephrostomies were removed. This technique is possible for extended pelvic obstruction. Blunt dissection with the endoscope is usualy blood less. This palliative procedure can be done in patients with poor general condition and allows for a better quality of life than nephrostomy or urinary diversions. PMID- 11774767 TI - [Complex vesicovaginal fistula. Report of 55 cases]. AB - OBJECTIVE: To specify the clinical and therapeutic peculiarities of complex vesico-vaginal fistulas. MATERIAL AND METHODS: 55 cases of complex vesico-vaginal fistulas are reported. After the clinical diagnostic all the patients had an intravenous excretory urogram. The fistulas were classified according to the Benchekroun classification. RESULTS: The mean age was 34 years (17-70 years). The diagnostic was made clinically in all the patients. Thirteen patients had an abnormal intravenous excretory urogram. The treatment was made by a vaginal way in 45 patients, by an abdominal way in three patients and by a mixed way in two patients. Four patients had an urinary diversion and one refused the treatment. Among the 50 patients whose fistula was treated, 44 (88%) were continent whom 26 (52%) after one operation, 15 (30%) after two operations and three (6%) after three operations. CONCLUSION: The complex vesico-vaginal fistulas as all the vesico-vaginal fistulas are diagnosed clinically. The intravenous excretory urogram is indispensable to search an associated ureteral lesion. The treatment is surgical and usually needs the interposition of a vascularised graft. PMID- 11774768 TI - [Martius' technique in the treatment of complex vesicovaginal fistula]. AB - Sixteen cases of vesicovaginal fistulae (including 14 urethrovaginal fistulae), were treated vaginally using Martius' procedure. The authors describe the technique for the interposition of a labial fat pad, between the bladder and the vagina. The results are good. Thirteen patients have been cured. In one case a second was necessary using Guittes technique. There was two failures. PMID- 11774769 TI - [Scrotal injuries. Report of 40 cases]. AB - Between 1986 to 1998, 40 patients, 16 to 52 years old, consulted for trauma of the scrotum. The trauma was closed in 36 cases. The trauma occurred by accident of traffic in 19 cases, an accident of work in seven cases, an accident during sport in seven cases, aggression in six cases and brawl in one case. The clinical symptomatology was dominated by inflammatory big scrotum or haematoma in the tunic. Ultrasound imaging was performed in 20 patients, showed a contusion of the testicle in five cases, haematoma of the scrotum in ten cases and albuginal rupture in two cases. Thirty patients underwent surgical repair. Five patients underwent orchidectomy. Atrophy of the testis occurred in two patients who underwent resection of the pulp and two others who had haematoma of the haematocele. PMID- 11774770 TI - [Role of celioscopy in the assessment and treatment of non-palpable testis in adults. Report of 2 cases]. AB - The authors reported two cases of impalpable testis in young mens. Laparoscopy is useful in both the diagnosis and the management of impalpable testes. Intraabdominal testicles can be removed laparoscopically if atrophic or can be partly devascularized by spermatic vessel clipping if apparently normal. A second stage vasal-based orchidopexy can then be performed once adequate testicular reperfusion via the the defferential pedicle is believed to have occurred. PMID- 11774771 TI - [Yolk sac tumor. Report of a case]. AB - Yolk sac tumor is rare in adult. We report a case in a young man aged of 23 years treated by orchiectomy, chemotherapy and retroperitoneal lymphadenectomy. Diagnosis is based on pathology who shows other cellular contingents. Treatment is based on orchiectomy and chemotherapy is indicated for residula masses. The prognosis is bad because metastasis is frequent. PMID- 11774772 TI - [Pathophysiology and therapeutic aspects of left ventricular "remodeling" in the post-infarct phase]. AB - Left ventricular remodeling is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors. Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction, cardiomyopathy, hypertension, or valvular heart disease. Postinfarction remodeling has been divided into an early phase within 72 hours and a late phase beyond 72 hours. The early phase involves expansion of the infarct zone, which may result in early ventricular rupture or aneurysm formation. Late remodeling involves the left ventricle globally and is associated with time-dependent dilatation, the distortion of ventricular shape, and mural hypertrophy. Hypertrophy and collagen degradation are adaptive responses during postinfarction remodeling. Myocardial repair is triggered by cytokines released from injured myocytes. Ventricular remodeling is influenced most by infarct artery patency. Once infarct evolution has occurred, pharmacological intervention, like ACE inhibition and beta-adrenoreceptor blocking agents, may minimize infarct expansion and ventricular dilatation and improve the long-term prognosis. PMID- 11774773 TI - [The role of dobutamine stress echocardiography in the clinical routine of a department of cardiology]. AB - BACKGROUND: The aim of this study was to assess the role of dobutamine stress echocardiography (SE) for diagnosis and therapy of coronary artery disease (CAD) in the routine practice of a cardiological department in which bicycle stress testing, scintigraphy and coronary angiography are available. METHODS: Between January 1997 and September 1998, 123 patients (79 men, 44 women, 60.1 +/- 9.9 years) underwent SE. SE-indication, SE-result and the consequence of the SE were registered. A telephone follow-up, asking for events and cardiac interventions, took place after at least one year. RESULTS: SE was performed in 57 patients with suspected CAD and in 66 patients with known CAD. The indications were inconclusive bicycle stress-testing or perfusion scintigrams (n = 77), search for hibernation (n = 22), discrepancy between presenting symptoms and results of previous investigations (n = 14) and preoperative risk stratification (n = 10). In the group with suspected CAD, the proportion of female patients was higher (p = 0.001), in the group with known CAD the proportion of male patients was higher (p = 0.002). SE showed an ischemic reaction in 35 patients, hibernation in 24 patients, no ischemic reaction in 56 patients and was inconclusive in 8 patients. The consequence of SE was recommendation for diagnostic coronary angiography (n = 27), revascularisation (n = 10), abstention from any invasive intervention (n = 77), noncardiac surgery (n = 9) and electrophysiological investigation (n = 1). During the investigated period, 955 bicycle stress-tests, 677 Thallium scintigrams and 987 coronary angiograms were carried out. During the follow-up (15 +/- 2.9 months) 4 patients died. In 6 patients cardiac interventions were carried out. No differences were observed regarding events and interventions depending on SE results and consequences. CONCLUSIONS: At a cardiological department SE plays a role if findings are inconclusive and if hibernation or operative risk is looked for. A negative SE result most commonly leads to abstention from invasive intervention. If the SE result is positive, the recommendation for invasive intervention is also influenced by the clinical symptoms and the size of the ischemically reacting myocardium. PMID- 11774774 TI - Dominant right ventricular infarction: is angioplasty the optimal therapeutic approach? AB - Approximately 30% of all acute inferior myocardial infarctions (AIMI) are accompanied by acute right ventricular infarction (ARVI) as a consequence of proximal right coronary artery (RCA) occlusion. Fifty per cent of all patients with ARVI manifest hypotension, jugular venous distension, and dyspnoea with clear lung fields, which is then considered as dominant acute RVI (ARVI). The in hospital mortality rate of patients with ARVI who are treated traditionally is very high. Thrombolytic therapy is relatively ineffective, while primary angioplasty is a more recent approach yet to be established as optimal treatment for patients with ARVI. Thirty-eight patients with dominant ARVI were admitted to our CCU over a period of 24 months. The patients were retrospectively divided into 3 groups according to treatment: Group I (n = 16): traditional treatment; Group II (n = 12): thrombolytic therapy (streptokinase); Group III (n = 10): angioplasty after urgent coronarography. We tested the difference in the number of deaths in all groups by the Fisher exact test. There was a significant difference in the number of deaths between Group I and Group III (P < 0.05). Mortality reduction was also noted between Group II and Group III, which, however, proved to be statistically insignificant. PMID- 11774775 TI - Prognostic significance of liver metastases as first site of generalisation in patients with breast cancer--a retrospective analysis. AB - Of 672 patients with metastatic breast cancer, 24 evaluable patients with primary liver metastases were analysed with regard to their prognostic variables and survival. In 50% of these patients, liver metastases were found within the first 8.5 months after the diagnosis of breast cancer. The median survival of 10 months (range 0-60+ months) was extremely unfavourable. The median survival of hormone receptor-positive patients (11 months) was significantly longer than that of patients with hormone-receptor-negative tumours (4 months) (P = 0.025). Patients with elevated lactate dehydrogenase (LDH), glutamic-oxaloacetic transaminase (GOT) (> 50 U/I), or bilirubin levels at diagnosis had a significantly shorter median survival than patients with normal laboratory parameters (P = 0.001, P = 0.047, and P = 0.056, respectively). This retrospective study confirms the short survival time for breast cancer patients with liver metastases as initial site of relapse. Hormone-receptor status and the laboratory parameters LDH, GOT, and bilirubin were identified as important prognostic factors for survival. PMID- 11774777 TI - Molecular and clinical characterisation of homocystinuria in two Austrian families with cystathionine beta-synthase deficiency. AB - The influence of the genotype on the phenotypic expression of homocystinuria due to cystathionine beta-synthase (CBS) deficiency is frequently unclear. We therefore investigated the genotype and the phenotype of CBS deficiency in two Austrian families also considering genetic polymorphisms with a putative association with vascular disease (MTHFR 677C-->T, MTHFR 1298A-->C, F5 1691G-->A, F2 20210G-->A) and response to therapy. We identified the CBS 833T-->C/1058C-->T and CBS 828ins104/1358del134 compound heterozygous genotype in our index patients. Both patients showed mental retardation and ectopia lentis. CBS 833T- >C/1058C-->T was associated with severe vascular complications, which was not the case for CBS 828ins104/1358del134. The patient with CBS 828ins104/1358del134 was negative for F5 1691G-->A, F2 20210G-->A, MTHFR 677C-->T, and MTHFR 1298A-->C, while the patient with CBS 833T-->C/1058C-->T was heterozygous for MTHFR 1298A- >C. A combination therapy including pyridoxine, folic acid, hydroxycobalamin, and betaine failed to lower total homocysteine plasma levels below 50 mumol/L in both patients. In summary, our study demonstrates that the CBS 833C/1058T-MTHFR 1298AC genotype can be related to severe vascular disease, while the CBS 828ins104/1358del134-MTHFR 1298AA genotype presents with a somewhat milder clinical phenotype. Both genotypes do not allow for normalisation of total homocysteine plasma levels following vitamin therapy. PMID- 11774776 TI - Early clamping of umbilical cord blood and foetal CD34 enrichment. AB - We describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34+ stem cells from umbilical cord blood, in order to determine the criteria for an excellent recovery with high proliferative ability and bone marrow reconstitution. After an obstetrician-based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies, negative selections, using the Stem Sep method, or with a positive cells selection owing to their surface CD34 antigens, using the Mini Macs system. An excellent recovery of haematopoietic progenitors- burst forming unit erythroid; colony-forming unit granulocyte and macrophage; and colony-forming unit granulocyte, erythroid, monocyte, and macrophage--inversely related to an increase in clamping time, was achieved using the Mini Macs system (54% of colonies with a 90% purity), while the recovery of haematopoietic progenitors was 35% (with a 80% purity) using the Stem Sep method. By clamping umbilical cord blood at an early stage, we obtained a greater number of CD34+ cells, and their clonogenic activity increased with enrichment. This is particularly useful considering that the number of CD34+ stem cells contained in a unit of placental blood is sufficient for transplanting into a child but not for an adult engraftment. Thus, using these methods, we obtain a larger number of CD34+ stem cells. This increases the possibility of reducing graft versus host disease in adult patients and produces survival rates similar to the ones we observed in transplantation of bone marrow from unrelated donors. PMID- 11774778 TI - Cerebrospinal-fluid lactate in adult mitochondriopathy with and without encephalopathy. AB - Despite improved diagnostic facilities, the diagnosis of mitochondriopathy (MCP) is sometimes difficult to establish. This study aimed to investigate whether CSF lactate can be of diagnostic help in this respect. Cerebrospinal-fluid (CSF) lactate and its relation to resting lactate and lactate stress testing were investigated in 26 MCP patients, aged 30-84 years. The upper reference limit of CSF lactate, obtained from 28 healthy subjects, was 1.6 mmol/l. Seven MCP patients (27%) had elevated CSF lactate. Five of these patients had central nervous system (CNS) abnormalities other than elevated CSF lactate. In two patients with increased cerebrospinal-fluid lactate, lactate stress testing was normal or could not be carried out. In conclusion, CSF lactate is elevated in one quarter of adult MCP patients. CSF lactate is preferentially elevated in patients with additional CNS abnormalities other than elevated CSF lactate. If the results for resting lactate or lactate stress testing are normal or unavailable, determination of CSF lactate may be of diagnostic support in single cases. PMID- 11774779 TI - [General physicians and general medicine: social image and public opinion]. AB - During the last two decades, importance of general practice of medicine was more recognised. The kind of interest was different between Health decision makers and population. For Health decision makers, revalorisation of general medicine is the better solution we could develop in order to improve efficiency of the health care financing systems. However, From the side of population social image of the general physician is going down. In order to investigate the population view point about general practitioner, we conduct a trial next to 289 persons living Tunis area. Peoples recognized to the general practitioner some qualities: Useful for first aid, he integrates all aspects of the morbidity, initiates best relations with his patients and appropriately manages medical files. In the other side, He's less qualified than the specialist to take appropriate decision, for monitoring and for the quality of communication with patients. He' also lack of technicality and investigation procedures. Ours results indicate how it is urgent to lead a reform of teatching of general medicine in the country. PMID- 11774780 TI - [Mortality due to smoking in Tunisia in 1997]. AB - In Tunisia, in spite of the high prevalence of the cigarette smoking among males, there consequences in term of mortality were not until evaluated. These last can be estimated from tobacco consumption data, mortality statistics and estimates of risks observed among populations of smokers in cohort studies. Numbers of deaths by causes have been estimated from WHO for 1998 year. Smoking prevalence have been estimated from a national survey conducted in 1996 by l'Institut National de Sante Publique and the National League against the Tuberculosis and the Respiratory Illness. Mortality attributable to tobacco in Tunisia has been estimated 6430 deaths. The effect of smoking are a lot more important at the man (5580 deaths), contributing to 22% of male deaths, that at the woman (850 deaths) contributing at 4% of the female deaths. The present mortality to tobacco is similar to certain developed countries as France or Canada. The consumption of cigarettes even though it recorded a light decrease during these last years, remain even elevated notably at the young. Then it is waited to see an increase of tobacco related deaths during the future decades. It is urgent to conduct an efficient politics against this tobacco epidemic by helping the smoker to stop smoking and preventing teenagers to begin to smoke. PMID- 11774781 TI - [Psychological aspects and details of care of patients on hemodialysis]. AB - Chronic renal failure and periodic hemodialysis, by the physical reach and the therapeutic imperatives that they mislead disrupt by several ways the universe of the patient. This one is confronted to changes, or even to aggressions that undergo his body, his domestic and socio-professional life, which is accepted in general with difficulty. Indeed, our survey that concerned 109 patients on chronic hemodialysis shows that the minor psychiatric pathology is frequent and can represent a source of problems as well for the patients that for the medical and nursing staff. Besides the analysis of minor psychiatric specificities revealed by a known measure instrument (the GHQ), this work insists on the importance to take account of this aspects with the aim to enhance management and holistic care of these patients. PMID- 11774782 TI - [Epidemiology of chronic arteritis of the lower limbs: multicenter study: report of 531 cases]. AB - Arteritis is a local finding of a general disease: atherosclerosis. To define the risk factors of this disease in Tunisia, 531 patients were collected by a multicenter retrospective study between January 1998 and December 1999. Most of our patients were male with a mean age of 62 years. The most important risk factor was tobacco with an incidence of 90%. Lipids and diabetes were less common. The association of risk factors is particularly dangerous. PMID- 11774783 TI - [Screening for carential anemia in pregnant women: prospective study. Report of 200 cases]. AB - To report the frequency and intensity of anemia in a population of pregnant tunisian women. Our retrospective study concern 200 patients collected from january to july 1999 in a population of pregnancies. Mean age was 30.1 years and 68.5% of patients consult in the third trimester with a 33.5% rate of multiparity. The frequency of anemia is 37.5%. Anemia was ferriprive in 97.3% and hypochromic in 24% of cases. Mean ferritinemia is 4.19 ng/ml after 24 weeks of amenorrhea with a marqued decrease in case of multiparity and pregnancy evolution. Mean transferrinemia is significantly low in anemic (3.98 g/dl) versus non anemic (3.60 g/dl) patients (< 0.05). The comparison of anemia with parity, the delay between two pregnancies and term of pregnancy showed a higher risk with multiparity, short delay between two pregnancies and advanced term. The frequency of anemia in tunisian pregnant women is relatively high, prevention is based on iron supplementation and hygienodietetic advices. PMID- 11774784 TI - [Kaposi's sarcoma in Tunisia. Review of 91 cases]. AB - The sickness of Kaposi's sarcoma (KS) knows, currently, a renewal of interest since the emergence of 2 new forms: the iatrogenic KS and the epidemic KS. Through a retrospective study on 21 years (1978 to 1998) we have tried to specify the epidemiologic and clinical characters of KS in Tunisia. Our study interests 91 patients: 85 cases of classic KS (94%), 4 cases of iatrogenic KS and 2 cases of epidemic KS. The incidence of iatrogenic KS in renal transplant recipients in our study is 1.9%. A male predominance is found in the 3 forms. The mean age of beginning was 60 years in classic KS and more lower in the 2 other forms (31 years in iatrogenic KS and 46 years in epidemic KS). A predominance of lesions in the lower limbs was found in the 3 forms. The visceral locations was more frequent in iatrogenic KS (3 cases) while it has been found in only 1 case of classic KS. In Tunisia, the classic KS is the most frequent form. In iatrogenic and epidemic KS, visceral lesions are frequent and must be researched systematically. PMID- 11774785 TI - [Sensitivity, specificity and prognostic value of CEA in colorectal cancer: results of a Tunisian series and literature review]. AB - In order to determine the sensitivity of CEA in the diagnosis of colo-rectal carcinoma, we studied a series of 48 patients with colo-rectal carcinoma (1992 1996). The sensitivity was at 52% with a reference value of 5 ng/ml and 68.7% for a reference value of 2.5 ng/ml. With a reference value of 5 ng/ml, the sensitivity of CEA was at 37% only for patients with colo-rectal carcinoma at Dukes B stage, 66.6% for patients at stage C and 75% for patients at stage D. The dosage of CEA was carried out with a sandwich immunoenzymatic technique in tube. There is no statistic significant correlation between the pre-operative rate of CEA and the localisation of the tumor and its histologic type; in contrast, it was significantly correlated with the ganglionnary metastasis. A significant relationship between the pre-operative rate of CEA and the Dukes stage was found for a reference value of 10 ng/ml but not for a reference value of 5 ng/ml. We calculated the specificity of the CEA for the cancers of colon and rectum which was at 76.98% with a reference value of 5 ng/ml and 86% with a reference value of 10 ng/ml. PMID- 11774786 TI - [Molar pregnancy. Retrospective study of 60 cases in Tunisia]. AB - To identify the epidemiologic, clinical end therapeutic particularities of molar pregnancies in Tunisia. A retrospective study of 60 cases of molar pregnancy Diagnosis of MP was base on elevated urine HCG level and/or histologic examination of uterine revision done for all patients. The incidence of MP is 1/793(60/47624) pregnancies. The mean age of patients was 31.7 years and 16 patients had more than 35 years. The metrorragia is the main symptom (91.6%). Excessive uterine enlargement and lutein ovarian cysts were observed respectively in 57 and 6.6% of cases. Human chorionic gonadotropin level was upper than 50,000 UI/l in 91.4% of cases. Ultrasonography contributed to diagnosis in 82.8% of cases. Histological findings were complete molar in 33 cases and partial molar in 27 cases. 6 of 33 patients having complete molar developed persistent gestational trophoblastic tumor. Actinomycin D induced complete remission in all cases. Molar pregnancy is a relatively common disease in Tunisia. Careful and reliable human chorionic gonadotropin monitoring is essential for the early detection of post molar persistent gestational trophoblastic tumor. PMID- 11774787 TI - [Adenomyosis: analysis of 35 cases]. AB - The authors suggest an analytic study of 35 cases of a adenomyosis discovered on operatory pieces of hysterectomy. The incidence over 28%. The pick of frequency is situated between 40 and 50 years old. The history of voluntary interruption of pregnancy and early abortion are found in 60% of cases. 8 patients have scary uterus post cesarean section or myomectomy. The symptoms and signs are dominated by vaginal bleeding which is found in 71% of cases. Pelvic pain is present in 34% of cases. The adenomyosis is rarely isolated. It is associated to uterine fibroma in 62% of cases. Their symptoms and signs are often the same. Hysterographie can head the diagnosis in 7% of cases. The endovaginal ultrasound and the IRM may help in the diagnosis. PMID- 11774788 TI - [Antenatal diagnosis and contribution of fetopathologic examination in the management of omphalocele]. AB - The omphalocele is an average coelosomie, frequency of which is estimated at 1/5000 births. We confront diagnosis antenatal with the exam foetopathologic in purpose of 41 cases of omphalocele brought together over a period going from January 1, 1991 till December, 2000 in the unity of foetopathologie from the CMNT. The frequency of omphaloceles is 4.88% of the children malformed and of 1.64% of the set (group) of the performed an autopsy children. An association malformative was found in 85.4% of cases and a karyotype typical aberration trisomie 13.18 and 21 was identified in 17% of cases. The preview of the children bearers of this deformation is especially bound (connected) to the existence and to the gravity of associated abnormalities. The omphalocele required a multidisciplinary making coverage intervernir obstetriciens, neonatologistes, surgeons pediatre and foetopathologistes. PMID- 11774789 TI - [Congenital coronary aneurysm. Report of two cases]. AB - Congenital coronary aneurysms are an unusual anatomical entity. Their prognosis appears to be particularly dependent on the presence or absence of aneurysm thrombosis. We report two cases of congenital coronary aneurysms, diagnosed in one case after myocardial infarction. The two patients were treated successfully by an exclusion of the aneurysm and coronary bypass. The aim of this study is to discuss the clinical features, prognosis and management of this disease. PMID- 11774790 TI - [Coronary artery disease in Takayasu's disease. Report of an operative case]. AB - A 39-years-old woman with Takayasu's arteritis confirmed by histological examination was admitted in our hospital because of angina pectoris. Selective coronary arteriograms reveled a 90% isolated stenosis in the right coronary ostium. The patient underwent a right coronary artery bypass grafting using the saphenious vein. The post operative clinical course was uncomplicated. On follow up over 14 months the patient has been completely free from anginal chest-pain. PMID- 11774791 TI - [Xanthogranulomatous pyelonephritis in pelvic kidney. A case report]. AB - We report the case of a xanthogranulomatous pyelonephretis in a pelvic ectopic kidney that is revealed by a buttockal abscess. PMID- 11774792 TI - [A rare complication of antineoplastic BCG therapy: pulmonary tuberculosis]. AB - Local treatment with intra vesical BCG for bladder carcinoma have few complications. Pulmonary side effects are rare, like interstitial pneumonitis. We report a case of a 77-year-old man, treated with BCG for bladder carcinoma who developed illness and tumoral chest-X-ray opacity. Mycobacterium tuberculosis bovis was isolated in culture and 2 years after in sputum. Physio pathologic mechanism of pulmonary features remains controversial, however this case suggest that lung lesions can be result of an infection process. PMID- 11774794 TI - The medicinal chemistry of the P2 receptor family. PMID- 11774793 TI - p38 MAP kinase: molecular target for the inhibition of pro-inflammatory cytokines. PMID- 11774795 TI - Radioligands for the study of brain 5-HT1A receptors in vivo. PMID- 11774796 TI - Discovery of montelukast: a once-a-day oral antagonist of leukotriene D4 for the treatment of chronic asthma. PMID- 11774797 TI - The histamine H3 receptor and its ligands. PMID- 11774798 TI - Isothermal titration calorimetry in drug discovery. AB - Isothermal titration calorimetry (ITC) follows the heat change when a test compound binds to a target protein. It allows precise measurement of affinity. The method is direct, making interpretation facile, because there is no requirement for competing molecules. Titration in the presence of other ligands rapidly provides information on the mechanism of action of the test compound, identifying the intermolecular complexes that are relevant for structure-based design. Calorimetry allows measurement of stoichiometry and so evaluation of the proportion of the sample that is functional. ITC can characterize protein fragments and catalytically inactive mutant enzymes. It is the only technique which directly measures the enthalpy of binding (delta H degree). Interpretation of delta H degree and its temperature dependence (delta Cp) is usually qualitative, not quantitative. This is because of complicated contributions from linked equilibria and a single change in structure giving modification of several physicochemical properties. Measured delta H degree values allow characterization of proton movement linked to the association of protein and ligand, giving information on the ionization of groups involved in binding. Biochemical systems characteristically exhibit enthalpy-entropy compensation where increased bonding is offset by an entropic penalty, reducing the magnitude of change in affinity. This also causes a lack of correlation between the free energy of binding (delta G degree) and delta H degree. When characterizing structure-activity relationships (SAR), most groups involved in binding can be detected as contributing to delta H degree, but not to affinity. Large enthalpy changes may reflect a modified binding mode, or protein conformation changes. Thus, delta H degree values may highlight a potential discontinuity in SAR, so that experimental structural data are likely to be particularly valuable in molecular design. PMID- 11774799 TI - The adenosine A3 receptor and its ligands. PMID- 11774800 TI - The Pan American Health Organization and World Diabetes Day. PMID- 11774801 TI - Incidence and prevalence of diabetes mellitus in the Americas. AB - OBJECTIVE: To present the incidence and prevalence of diabetes mellitus in the Americas as found through a thorough review of published information on the subject. METHODS: Data were obtained through a comprehensive review using the MEDLINE and BIREME bibliographical databases. In addition, government publications, conference reports, and meeting documents were identified by contacting government and nongovernmental organizations and other institutions. Incidence and prevalence rates were adjusted by age and sex, when possible, by the direct method using the world Segi population as the standard. The 95% confidence intervals were calculated using the Poisson distribution or the normal distribution. RESULTS: Diabetes mellitus represents a major public health problem in the Americas, and there is evidence that its prevalence is increasing in some countries. CONCLUSIONS: Given that most Latin American and Caribbean nations are experiencing a demographic transition, it is expected that the prevalence of diabetes will continue to increase rapidly in the near future. Despite the economic constraints faced by the countries of the Americas, there is a clear need for more efforts in the area of diabetes prevention and control. PMID- 11774802 TI - [Evaluation of the quality of care for diabetic patients in Latin America]. AB - OBJECTIVE: To make a preliminary diagnosis of the quality of care that individuals with diabetes mellitus (DM) received in participating centers of the QUALIDIAB network in Latin America and the Caribbean, and to assess the potential usefulness of this information as well as the importance of expanding the QUALIDIAB network. METHODS: A total of 13,513 patient records from the QUALIDIAB network were analyzed, from public and private health care entities and from the Social Security systems of Argentina, Brazil, Chile, Colombia, Paraguay, and Uruguay. The study utilized: 1) quality-of-care indicators based on international reference values, 2) patient information on clinical, biochemical, and therapeutic parameters and on the rate of use of diagnostic and therapeutic materials, 3) a computer database program, and 4) a software program for statistical analysis. RESULTS: Among the patients studied, about half of them had suffered from diabetes for 5 years or less; this was true both for persons with type 1 diabetes (DM1) and for those with type 2 diabetes (DM2). Of the persons with DM1, 24% of them had a blood glucose level of < 4.4 mmol/L; this was true for 15% of those with DM2. The proportion of persons with a blood glucose level of > 7.7 mmol/L was 41% among those with DM1 and 57% among those with DM2. The frequencies of association between DM2 and other cardiovascular risk factors were: overweight/obesity, 59%; hypertension, 60%; total cholesterol > 5.5 mmol/L, 53%; high-density lipoprotein cholesterol < 1 mmol/L, 32%; triglycerides > 1.7 mmol/L, 45%; and smoking, 13%. Of the people with DM1, 20% of them had a body mass index < 19 kg/m2, probably reflecting deficient metabolic control and inadequate insulin intake. The systematic checking of metabolic control, other cardiovascular risk factors, and chronic DM complications was inadequate in from 3% to 75% of the cases, depending on the specific aspect considered. According to various patient-therapy-education indicators, only some one-quarter to one-half of the studied patients could play an active, effective role in DM control and treatment. Of the persons with DM1, 50% of them were treated with a mixed dose of insulin (NPH + regular insulin), administered in two daily injections in 43% of the cases. Among the patients, 5% of them received one daily insulin injection, and 9% of them received three daily insulin injections. Of the people with DM2, 13% of them treated it only with diet and 14% just with insulin. Among the patients receiving drug treatment, the oral hypoglycemics most used in monotherapy were sulfonylureas (33%), biguanides (9%), and a combination of these two (14%). Fewer than half of the people with diabetes received drug therapy for the associated cardiovascular risk factors. The frequency of patients' macroangiopathic and microangiopathic complications increased with the duration of their disease. Comparing patients who had had diabetes for 5 years or less with those who had had the illness for more than 20 years, the frequency of renal insufficiency and of amputations was around 7 times as great in the latter group; for peripheral neuropathy, it was 2 times as great, and for stroke 1.6 times as great. CONCLUSIONS: These results show the need to improve the quality of care for diabetic patients in Latin America and the Caribbean, and that QUALIDIAB could help do this. Expanding the QUALIDIAB network will help to more accurately diagnose the quality of that care in the Americas, and it will facilitate interventions aimed at optimizing the care. This, in turn, will improve the quality of life of persons who suffer from diabetes as well as diminish the socioeconomic costs of the disease. PMID- 11774803 TI - Diabetes in Bolivia. AB - OBJECTIVE: To measure the prevalence of diabetes mellitus (DM), hypertension, obesity, and related risk factors in major cities in Bolivia. METHODS: A population-based survey was conducted in four Bolivian cities: La Paz, El Alto, Santa Cruz, and Cochabamba. The total sample size was chosen to be 2,948 persons. The overall response rate was 86%, with the rate varying somewhat among the four cities. DM was diagnosed through an oral glucose tolerance test (OGTT) 2 hours after an overload of 75 grams of glucose, using World Health Organization criteria. RESULTS: The overall prevalence of DM in the four urban areas combined was 7.2% (95% confidence interval (CI): 6.2%-8.3%) and of impaired glucose tolerance (IGT) was 7.8%. A total of 73.1% (95% CI: 65.0%-81.0%) of those previously diagnosed with DM and 73.7% (95% CI: 61.0%-86.4%) of newly diagnosed cases were overweight, according to measurements of body mass index. Hypertension was found in 36.5% (95% CI: 27.6%-45.5%) of known diabetics and in 36.6% (95% CI: 23.0%-50.1%) of newly diagnosed cases, compared to only 15.9% (95% CI: 14.3% 17.5%) among people without DM. The disease was most common among older persons and those with little education. CONCLUSIONS: Diabetes is a genuine public health problem in Bolivia. Further, the high prevalence of IGT that was found suggests that diabetes prevalence will increase in the near future in the country unless prevention strategies are implemented. PMID- 11774804 TI - [National campaign to detect suspected diabetes cases in Brazil: a preliminary report]. AB - The Ministry of Health of Brazil is implementing a National Plan for the Reorganization of Health Care for Hypertension and Diabetes Mellitus, with the aim of reducing the morbidity and mortality associated with diabetes. This plan is divided into four stages, one of which was a national campaign to detect suspected diabetes cases that was carried out in March and April 2001. This was the first survey of its kind carried out by public health services in Brazil, and the preliminary results are described in this article. Out of a total of 5,507 participating municipalities, 4,446 of them (81%) submitted data to the Ministry of Health. Twenty million people were tested (71% of the target population), and 3.3 million of them were identified as possibly having diabetes. The campaign will contribute towards restructuring the systematic and resolution-oriented care that the national, public Unified Health System provides to diabetics. The preliminary results confirm that diabetes is one of the main health problems in Brazil. Priority should be given to preventing type 2 diabetes. PMID- 11774805 TI - [An intervention to improve diabetes control in Chile]. AB - OBJECTIVE: Previous research has shown that controlling blood glucose improves short-term and long-term outcomes among patients who have either type 1 or type 2 diabetes. The objective of this study was to investigate, in a developing country, the effectiveness of an intervention that included patient education, self-monitoring of blood glucose, and determination of the level of glycosylated hemoglobin (HbA1c). METHODS: The patients were grouped into three categories, taking into account such clinical manifestations as the duration of their diabetes, its treatment, and their hospitalization history. After the inclusion and exclusion criteria were applied, the persons were randomly assigned to two groups. One group (210 patients) received the educational intervention, and the control group (206 patients) received customary care. The intervention group received educational information needed for self-monitoring of blood glucose and for the self-evaluation of positive and negative behaviors related to metabolic control of the disease. RESULTS: The two groups were similar with respect to age (mean of 52.3 and 50.5 years) and to the proportion of patients with type 1 diabetes (13.8% and 16.0%). There were no initial differences in the average concentration of HbA1c in the two groups (8.9% +/- 0.1% and 8.9% +/- 1.4%). A total of 50 persons dropped out of the study, 14.8% of those in the intervention group and 9.2% of those in the control group. In the intervention group, compliance with dietary recommendations increased by 43.5%, from 57.5% at the beginning of the study to 82.5% at the end (P < 0.001); in the control group there was also a change but it was not significant. Although patients with a high initial HbA1c concentration were underrepresented in this study, the average HbA1c concentration declined significantly in the intervention group (-0.4% +/- 1.1%, P = 0.001) but not in the control group (-0.1% +/- 0.1%). CONCLUSIONS: In one developing country, educating patients about diabetes helped improve metabolic control, a fact that can be attributed mainly to the intervention's positive impact on those persons' diet. PMID- 11774806 TI - Capture-recapture method to estimate lower extremity amputation rates in Rio de Janeiro, Brazil. AB - OBJECTIVE: To estimate rates of lower extremity amputations (LEAs) in persons with peripheral vascular disease, diabetes mellitus, trauma, neoplasm, osteomyelitis, or emphysematous gangrene. METHODS: Regional amputee registries were used to estimate the rate of lower extremity amputations with the capture recapture (CR) technique. Data were extracted from three amputee registries in Rio de Janeiro: source 1, with 1,191 cases from 23 hospitals; source 2, with 157 cases from a limb-fitting center; and source 3, with 34 cases from a rehabilitation center. Amputee death certificates from source 1 identified 257 deaths from 1992 to 1994. Three CR models were evaluated using sources 2 and 3. In order to avoid an overestimation of the rate of LEAs, two models were applied for the data analysis: in one case, deceased patients listed in source 1 were excluded from the model, and in the other case, deceased patients were included as well. RESULTS: Excluding the 257 deaths, the estimated number of amputations in the municipality of Rio de Janeiro from 1992 to 1994 was 3,954, for a mean annual incidence rate of 13.9 per 100,000 inhabitants. Among persons with diabetes, the annual incidence rate of lower extremity amputations was substantially higher (180.6 per 100,000 persons per year), representing 13 times the risk of individuals without diabetes. The yearly rate of LEAs according to the routine surveillance system was estimated at 5.4 and 96.9 per 100,000 in the general population and in diabetics, respectively. If data from the three registries are added, 1,382 patients with LEAs were identified, with the reasons for the amputations distributed as follows: peripheral vascular disease = 804 (58.1%); diabetes mellitus = 379 (27.4%); trauma = 103 (7.4%); osteomyelitis = 44 (3.1%); gangrene = 36 (2.6%), and neoplasm = 16 (1.1%). CONCLUSIONS: These findings show a high incidence of LEAs in Brazil, when compared to countries such as Spain, that is attributable mainly to peripheral vascular disease and diabetes mellitus. PMID- 11774807 TI - [Standards for developing diabetes education programs in the Americas]. AB - The Declaration of the Americas (DOTA) recognizes the severity of diabetes in the Region of the Americas and the commitment of the governments of the Region to implement strategies and actions that can reduce the socioeconomic cost of diabetes and improve the quality of life of those who suffer from the disease. Given that, there is a need to incorporate diabetes education as an indispensable medical service in order to achieve the active participation of patients in controlling and treating the disease. The DOTA Education Committee prepared this document to specify the conditions and standards that a patient diabetes education program should meet. PMID- 11774808 TI - [Burn shock and initial management]. PMID- 11774809 TI - [The influence of resuscitation with solutions containing different concentrations of sodium on the homeostasis of burn patients during the early postburn stage]. AB - OBJECTIVE: To investigate the influence of resuscitation with solutions containing different concentrations of sodium on the homeostasis of burn patients during the early postburn stage. METHODS: Thirty-five cases of burn patients inflicted with 50% approximately 100% of TBSA including 20% approximately 88% of 3rd degree burn were enrolled in the study. All the patients studied were divided into A[(Na+) = 174 mmol/L] and B [(Na+) = 130 mmol/L] groups according to different concentrations of sodium in the infusion solution. The input of the fluid, plasma crystal osmotic pressure, plasma ratio of albumin to globulin, urine output and pH value and anasarcous degree were observed during 1 to 5 postburn days (PBDs). RESULTS: The infusion fluid amount per hour in A group was 20 approximately 30 ml less than that in B group within 3 PBDs. The infused sodium amount in A group was more than that in B group within 5 PBDs. The FENa in A group was in normal range within 5 PBDs, while that in B group was lower than normal. This might be related to different infusion amounts of water and sodium. CONCLUSION: The homeostasis of burn patients could be significantly affected by the water load and the sodium concentration in the resuscitation solution during early postburn stage. PMID- 11774810 TI - [A clinical study on the effects of delayed rapid fluid resuscitation on the blood circulation during postburn shock stage]. AB - OBJECTIVE: To explore the protocol for the quick correction of postburn shock in case of delayed resuscitation. METHODS: Twenty burn patients inflicted with 40% or bigger TBSA burn, and who were in shock due to delayed admission to hospital, were enrolled in the study. The patients were treated by delayed rapid fluid resuscitation. The amount of infused fluid and urine output was observed. The indices of hemodynamics and oxygen metabolism, i.e. arterial blood pressure (BP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), central venous pressure(CVP), cardiac output (CO), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction (O2ext), lactic acid (LA) and base deficit (BD) were monitored at the shock stage(1 approximately 48 PBHs). RESULTS: The amount of rapid fluid infusion within 2 hours after admission accounted for (38.8 +/- 6.1)% of the amount calculated with the formula (The Third Military Medical University burn shock fluid infusion formula) for the 1st 24 PBHs. When the amount of prehospital infusion was added, the amount would be (48.3 +/- 5.0)% of the amount for the 1st 24 PBHs. The real amount of the infusion for the 1st 24 PBHs was (31.4 +/- 14.3)% more than that of the formula amount, and the real infused fluid amount for the 2nd 24 PBHs was (3.2 +/- 7.2)% more than that of the formula amount. After rapid fluid infusion, there exhibited remarkable increase in urine output, CO and DO2 with evident decrease in SVR, LA and BD. Furthermore, PAWP, PAP and CVP remained within normal range even though PVR increased significantly after rapid fluid infusion. CONCLUSION: In case of shock or compulsory delayed resuscitation, rapid fluid resuscitation during early postburn stage was beneficial with critical hemodynamic monitoring. The amount of delayed rapid fluid infusion was much increased than routine. Hemodynamic indices such as CO, PAP, PAWP and CVP were employed as the guidelines for delayed rapid resuscitation with reference to some clinical indices such as serum LA, blood gas analysis and urine output. PMID- 11774811 TI - [An experimental study on the delayed resuscitation of dogs with burn shock]. AB - OBJECTIVE: To explore the effects of delayed resuscitation on burn shock with ringer's solution. METHODS: Twelve mongrel dogs were randomly divided into control (S, n = 6) and treatment (LR, n = 6) groups. The dogs in LR group were inflicted by 35% TBSA III degree burn and were resuscitated with Lactate Ringer's solution. Urine output in amount of 1 ml.kg-1.h-1, and cardiac output at level of 70% approximately 80% of pre-burn level were referred for the modulation of the speed and amount of fluid infusion. The postburn changes of volumetric load, mean arterial pressure (MAP), LVSP +/- dp/dtmax, CI, DO2 and VO2 during the first 24 hours of resuscitation were observed. RESULTS: The infusion amount of LR solution was 8.87 +/- 1.02 ml/kg per 1% TBSA during the first 24 hours of resuscitation, which was 1.2 times more than that with Parkland formula. Furthermore, the infusion fluid amount within the first 4 hours of resuscitation was (3.63 +/- 0.99) ml.kg(-1).1% TBSA-1, which was 41% of total amount within the first 24 hours. MAP, LVSP, +/- dp/dtmax, CI, DO2 and VO2 reached or approached the levels in S group within 2 hours of resuscitation. CONCLUSION: The infusion amount of Lactate Ringer's solution needed in delayed resuscitation was larger than that in early resuscitation. And the indices of hemodynamics and myocardial mechanics were improved obviously within 2 hours of resuscitation. PMID- 11774812 TI - [An experimental study on the change in cardiac sympathetic neuroelectrophysiology in severely scalded rats during early postburn stage]. AB - OBJECTIVE: To investigate the mechanism and the rule of the change in cardiac sympathetic neuroelectrophysiology in severely scalded rats during early postburn stage, so as to explore the relationship between the change and postburn severe cardiac injury. METHODS: Forty-four Sprague-Dawley rats were randomly divided into normal (n = 6), sham injury (n = 8) and scalded (n = 20) groups. The rats in scalded group were inflicted by 30% TBSA III degree burn on the backs. The electric discharge activity of cardiac sympathetic nerve was observed and recorded by neuroelectrophysiological technique. The changes in ECG and myocardial mechanic indices were simultaneously observed. RESULTS: The activity of efferent cardiac sympathetic nerve increased immediately after scalding, but that of the afferent nerve increased obviously after about 90s incubation period. The activity of efferent nerve further increased after the increase of afferent activity, and this increase in both efferent and afferent nerves lasted for about 3 hours and decreased evidently thereafter. The change of afferent nerve was earlier than that of efferent nerve. The average electric discharge activity of cardiac sympathetic nerve increased with obvious fluctuation, which exhibited intermittent burst pattern at 1 PBH in some rats, in which frequent ventricular extrasystole appeared accompanying with the simultaneous increase in electric discharge burst in 4 rats. The postburn LVDP and +/- dp/dtmax in rats decreased significantly. CONCLUSION: The activities of both efferent and afferent cardiac sympathetic nerve increased dramatically in the early postburn stage. The change in efferent nerve activity could be affected to some degree by that of afferent nerve. This implied that the increase of the neuroelectrophysiological activity of cardiac sympathetic nerve might be one of the causes of early severe postburn cardiac injury. PMID- 11774814 TI - [The change in the plasma contents of adrenomedullin and endothelin in burn patients during early postburn stage]. AB - OBJECTIVE: To observe the change in the plasma contents of adrenomedullin (ADM) and endothelin (ET) in burn patients, so as for us to explore their roles in the pathogenesis in the physiological disturbance in burn patients. METHODS: The plasma concentrations of ADM and ET were determined at 6, 12, 24 and 48 postburn hours (PBHs) in 40 burn patients with radioimmunoassay (RIA) and compared with those of 25 healthy people. RESULTS: The postburn plasma levels of ADM and ET in burn patients increased immediately after injury, and they were positively correlated to burn area. The plasma ADM reached peak level at 12 PBHs and decreased thereafter, but remained at higher level than that in healthy people at 48 PBHs (P < 0.01). Plasma ET increased to top level at 6 PBH and decreased thereafter. But it remained at high level at 48 PBHs in severe burn patients (burned area larger than 45% TBSA) (P < 0.05 approximately 0.01). The plasma levels of ET and ADM increased proportionally and their ratio was close to that in normal control, but it decreased obviously after 6 PBH in all groups (P < 0.01). CONCLUSION: There were evident postburn changes in plasma ADM and ET contents, and the results implied that ADM and ET played some roles in the development of postburn physiological disturbance. PMID- 11774813 TI - [The effects of resuscitation with hypertonic saline solution on the postburn pulmonary injury in scalded dogs]. AB - OBJECTIVE: To explore the preventive and curative effects of resuscitation with hypertonic saline solution on postburn pulmonary injury in scalded dogs. METHODS: Mongrel dogs inflicted by 40% TBSA III degree scald were employed as the model. Sixteen dogs were randomly divided into two groups with 8 in each group, i.e. hypertonic saline solution group (H group) and isotonic saline solution (N group). The changes in cardiac output (CO), cardiac index (CI), pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) were determined within 48 postburn hours (PBHs). Pulmonary tissue samples were obtained for the measurement of pulmonary water and hydrocarbon (C2 H4 and C2 H6) contents. Bronchoalveolar lavage fluid (BALF) was harvested for white blood cell (WBC) counting and classification and for the detection of the changes in PLA2 activity and LTC4 content. RESULTS: Compared to those in N group, the CO and CI in H group increased significantly while the pulmonary water content, the hydrocarbon content, the WBC count, and PLA2 activity and LTC4 content in BALF all decreased obviously. CONCLUSION: Hypertonic saline solution might be beneficial in the management of early postburn pulmonary injury. PMID- 11774815 TI - [Effects of nitric oxide (NO) on the cardiac function in severely scalded rats]. AB - OBJECTIVE: To investigate the effects of NO on the cardiac function in severely scalded rats and to elucidate its mechanism. METHODS: Ninety Sprague-Dawley (SD) rats inflicted with 30% TBSA III degree scalding were employed as the model and divided randomly into five groups, i.e. burn (B), shamburn (SB), L-arginine (L Arg), N-nitroso-L-argininemethylester (L-NAME) and L-Arg + L-NAME groups. Cardiac functional indices, myocardial content of malondialdehyde (MDA) and myocardial Ca (calcium) transport were examined in the rats of all the groups, respectively. RESULTS: Compared to those in B group, the mean arterial pressure (MAP), left ventricular summit pressure (LVSP), the +/- dp/dt max in left ventricle pressure and the cardiac Lo in L-NAME group increased obviously. While those in L-Arg group decreased significantly but those in L-Arg + L-NAME group exhibited no remarkable change. The MDA content in L-NAME group was evidently lower than that in B group, while the calcium transport index of sarcoplasmic reticulum in L-NAME group increased obviously. CONCLUSION: Nitric oxide, massively produced postburn, exerted inhibitory effects on cardiac function by means of the cytotoxicity of its owns and other free radicals, which might be closely related to the decrease of its calcium transport function of sarcoplasmic reticulum. PMID- 11774816 TI - [The dynamic change in the expression of interleukin 18 mRNA in the tissue of scalded rats after delayed resuscitation]. AB - OBJECTIVE: To explore the dynamic change in the expression of interleukin 18 (IL 18) mRNA in the tissue of scalded rats after delayed resuscitation. METHODS: Wistar rats inflicted by 30% TBSA III degree scalding were employed as the model. Fifty-four rats were randomly divided into normal control (C), scalding and delayed resuscitation group (SD) and preventive group of selective decontamination of digestive tract (SDD) group. The RT-PCR was applied to determine the tissue contents of IL-18 mRNA in intestine, lungs, liver and kidneys at 2, 8, 16 and 24 PBHs. RESULTS: Plasma level of LPS increased significantly and reached summit level at 8 and 24 PBHs after delayed resuscitation after scalding (P < 0.01), but decreased obviously (P < 0.05) after the preventive application of SDD. Furthermore, the expression of tissue IL-18 mRNA in lungs, liver and kidneys since 2 PBHs increased evidently when compared to that before scalding and reached peak value at 8 PBH (P < 0.01) and lasted up to 24 PBHs. The expression of IL-18 mRNA could be inhibited to varying degrees by preventive application of SDD (P < 0.05-0.01). It was indicated by correlative analysis that plasma level of LPS was positively correlated to the expression of tissue IL-18 mRNA in intestine, lungs and liver (r = 0.298, 0.290 and 0.365 respectively with P < 0.05-0.01). CONCLUSION: The expression of tissue IL-18 mRNA in intestine, lungs, liver and kidneys increased significantly during early postburn stage and progressively enhanced thereafter. And the expression of tissue IL-18 mRNA in a variety of body tissue was significantly affected by post traumatic endotoxemia. PMID- 11774817 TI - [An experimental study on the recombinant composite skin graft consisting of human epithelium and acellular xeno-dermis]. AB - OBJECTIVE: To observe the effects of the recombinant composite skin graft consisting of human epithelium and acellular xeno-dermis on full thickness skin loss wounds, so as to find a new wound covering material. METHODS: Forty-two nude mice with full thickness skin loss on the back were grafted with the composite skin (compound skin grafting group, G) and human keratinocyte sheet (control group, C), respectively. The wound healing conditions, such as wound healing rate and wound contraction rate, were observed at different time points after the operation. Simultaneously, wound tissue samples were harvested for histological examination. RESULTS: The wound healing rate in G group was much higher than that in C group. In contrast, the wound contraction rate in G group was obviously lower than that in C group (P < 0.05). It was indicated by histological examination that there was full differentiation of epithelium, orderly collagen proliferation and obvious reconstruction of the epithelial-dermal conjunction structure in G group. There was no obvious sign of acute immune rejection. CONCLUSION: The wound covering with recombinant composite skin graft of human epithelium and acellular xeno-dermis could improve wound healing quality. The composite skin could be a new skin substitute. PMID- 11774818 TI - [Morphological changes and quantitative DNA analysis of Schwann cells in peripheral nerves after high voltage electrical injury]. AB - OBJECTIVE: To explore the characteristics and the mechanism of the injury of Schwann cells and nerve fibres of the peripheral nerves inflicted by high voltage electricity. METHODS: Rabbits injured by high voltage electricity were employed as the model. Thirty rabbits were randomly divided into control (9) and experimental (21) groups. The dynamic quantitative DNA analysis and the change of the morphology and structure of the sciatic nerve were observed with LM and EM on 0, 3, 7, 10, 14 and 21 postburn days (PBDs), respectively. RESULTS: There was continuous degeneration of the axon and medullary sheath of sciatic nerve tissue and its neogenesis was inhibited. The DNA synthesis in Schwann cell initiated on 3 postburn day (PBD). The distribution of the current was heterogeneous on the cross section of peripheral nerve fibres. CONCLUSION: The obvious features of peripheral nerve injured by high voltage electricity included delayed initiation of the DNA synthesis of Schwann cell and the secondary necrosis and inhibition of neogenesis process of Schwann cell. PMID- 11774819 TI - [Screening of aberrant genes of immunocytes in severely scalded rats by inhibition of subtractive hybridization]. AB - OBJECTIVE: To explore the relationship between the postburn changes of gene expression of immunocytes and postburn immunological functional disturbance in severely scalded rats. METHODS: Immunocytes of female F344 rats with severe scalding were harvested and the mRNA was extracted for the inhibition of the expression of aberrant gene selected by subtractive hybridization in contrast to that before scalding. The aberrant genes were cloned and sequenced and compared to those in Genebank for homology. RESULTS: The harvested immunocytes were identified by LM to be monocytes and lymphocytes. Multiple strips located at 200 approximately 400 bp were obtained by inhibiting subtractive hybridization and were cloned into PGEM-T easy plasmid vector. Thus the genebank of aberrant expression was constructed. Twenty clones were sequenced randomly and partial obtained known genes were in accord with postburn systemic changes. Several novel genes were accepted and registered by Genebank. CONCLUSION: There exhibited change in the gene expression of peripheral immunocytes at early postburn stage in rats inflicted by severe burn. PMID- 11774820 TI - [Modulating effects of thymopentin on the immune system of severely burned patients]. AB - OBJECTIVE: To explore the modulating effects of thymopentin (TP-5) on the immune system of severely burned patients. METHODS: Sixty patients with severe burn were enrolled in this study and were randomly divided into treatment (T, n = 30) and control (C, n = 30) groups. The T lymphocytes and NK cells in peripheral blood in two groups were determined on the 2, 5, 8, 15 and 22 postburn days (PBDs). The patients in T group were treated with TP-5 in a dose of 1 mg/d for 20 days beginning on 2 PBD. RESULTS: There was no difference of T lymphocytes and NK cells between the two groups on 2 PBD, and there was no difference of total number in T lymphocytes between the two groups on 5, 8, 15 and 22 PBDs. But the NK cell number and CD4/CD8 ratio in C group were much lower than those in T group. CONCLUSION: The function of T lymphocytes and NK cells in severely burned patients could be obviously improved by TP-5, which played immune modulating roles. PMID- 11774821 TI - [Effects of quinacrine on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury]. AB - OBJECTIVE: To explore the influence of quinacrine, which is an inhibitor of phospholipase A2, on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury. METHODS: Forty-two Wistar rats were randomly divided into normal control (C, n = 6), gut ischemia/reperfusion injury control (IC, n = 12), quinacrine use at 3 hours after the injury(3 h, n = 12), and quinacrine use at 12 hours after the injury (12 h, n = 12) groups. The contents of blood endotoxin and TNF alpha in venae cavae and portal vein were measured in all groups. At the same time, tissue samples from mesenteric lymph nodes, liver, lungs and kidneys were harvested for bacterial culture. RESULTS: Plasma contents of endotoxin and TNF alpha were lowered in both quinacrine treatment groups (P < 0.01). The incidence of bacterial/endotoxin translocation was decreased by quinacrine use in mesenteric lymph nodes, lungs, liver and kidneys after the injury (P < 0.05 approximately 0.01). CONCLUSION: Early application of quinacrine in Wistar rats inflicted by gut ischemia reperfusion injury could obviously lower bacterial/endotoxin translocation and ameliorate the release of pro-inflammatory mediators and cytokines, thus attenuating injury to remote organs. PMID- 11774822 TI - [The postburn changes of the plasma levels of PGE2 and TNF alpha in burn patients]. AB - OBJECTIVE: To explore the postburn changes of the plasma levels of PGE2 and TNF alpha and their relationship with burn severity and sepsis. METHODS: Twenty-four burn patients were enrolled in the study and were randomly divided into four groups based on burn area and sepsis in reference to normal group (10 healthy adult volunteers). The plasma levels of PGE2 and TNF alpha at different postburn time points in all burn patients and in healthy volunteers were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: The postburn plasma PGE2 level increased in most patients but decreased in the patients with major burn or sepsis, even to the level lower than that in normal control. On the other hand, the postburn plasma TNF alpha level increased in all patients, especially obvious in those with sepsis. And the changes were not correlated to burn area and postburn time. Moreover, the postburn plasma TNF alpha level was negatively correlated to that of PGE2. CONCLUSION: Decreased postburn plasma PGE2 level was correlated to high incidence of burn sepsis. And PGE2 might down-regulate TNF alpha production. PMID- 11774823 TI - The impact of geriatric post-discharge services on mental state. AB - OBJECTIVE: To determine the impact of geriatric post-discharge services on mental state. METHODS: Three computer databases, MEDLINE, HealthSTAR and the Cochrane Database of Systematic Reviews were searched for relevant articles; the bibliographies of retrieved articles were searched for additional references. RESULTS: 11 trials were located that met the four inclusion criteria: (i) original study; (ii) published in English or French; (iii) controlled trial (randomized or non-randomized) of a geriatric post-discharge service; and (iv) including at least one measure of mental state. All trials met most of the validity criteria for intervention studies of the Evidence-Based Medicine Working Group. Three trials reported a small effect on emotional state or self-perceived health and eight trials reported no effect. CONCLUSION: There is little evidence that geriatric post-discharge services have an impact on the mental state of aged subjects. Future services and studies should be designed to address the issue of mental state outcomes in this population. PMID- 11774824 TI - Report of the 20th Workshop of the AIDPIT Study Group (Artificial Insulin Delivery Systems, Pancreas and Islet Transplantation). PMID- 11774825 TI - A set of three clinical tests can detect the presence or absence of rotator cuff tears. PMID- 11774826 TI - Individual tests from the history and physical examination are inaccurate in diagnosing rotator cuff tears. PMID- 11774827 TI - Massage is better than acupuncture (and in the short term better than self care) in reducing pain and disability in patients with chronic lower back pain. PMID- 11774828 TI - Spinal manipulation and exercise for chronic neck pain: are they more effective when delivered alone or in combination? PMID- 11774829 TI - [Ophthalmia neonatorum]. PMID- 11774830 TI - [Eye injuries in children]. PMID- 11774831 TI - Spare post-exposure prophylaxis with round-the-clock HIV testing of the source patient. AB - After occupational exposures, immediate HIV testing of source patients may avoid the unnecessary use of post-exposure prophylaxis (PEP). Two time periods were compared. Before the availability of 24 h a day immediate testing, PEP was initiated after 12.6% of exposures, compared with 3.7% during the second period. The adjusted relative odds ratio of PEP during the second compared with the first period, was 0.23. The availability of immediate HIV testing limits unnecessary occupational PEP. PMID- 11774832 TI - Africans in London continue to present with advanced HIV disease in the era of highly active antiretroviral therapy. AB - Our findings show that despite the numerous advances in the management of HIV disease, this has not resulted in earlier presentation in Africans or non Africans. African patients are still presenting with significantly more advanced disease than non-Africans, and are more likely to have AIDS at presentation in 1998-1999 than in 1982-1995. An urgent need exists to identify the factors associated with delayed presentation, both to optimize clinical outcomes and reduce the possibility of onward transmission. PMID- 11774833 TI - The nuclear factor kappa B and Spl binding sites do not appear to be involved in virus suppression by CD8 T lymphocytes. AB - CD8 T lymphocytes suppress primate lentivirus replication in a non-cytotoxic manner. This antiviral activity, mediated by a CD8 cell antiviral factor (CAF), involves an arrest in viral transcription. Present studies indicate that the CD8 T cell non-cytotoxic antiviral activity and CAF inhibit the replication of an SIV mutant virus lacking the nuclear factor kappa B (NF-kappaB) and Spl binding domains. The results strongly suggest that the NF-B and Spl binding sites are not involved in virus suppression by CD8 T lymphocytes. PMID- 11774834 TI - Elevated levels of CD4+CD7- T cells in HIV infection add to the prognostic value of low CD4 T cell levels and HIV-1-RNA quantification. PMID- 11774835 TI - Successful control of subfulminant hepatitis related to lamivudine-resistant hepatitis B virus in an HIV-infected patient. PMID- 11774836 TI - Agranulocytosis and fever seven weeks after starting abacavir. PMID- 11774837 TI - Liver abscess caused by Stenotrophomonas (Xanthomonas) maltophilia in a patient with AIDS. PMID- 11774838 TI - Elevated serum pregnancy zone protein levels in HIV-1-infected men. PMID- 11774839 TI - Low risk of pancreatitis in HIV-infected patients on hydroxyurea plus didanosine. PMID- 11774840 TI - A compromise strategy for patients with multiple drug failure. PMID- 11774841 TI - 1,4,7,10-tetrakis(2,2'-bipyridyl-5-ylmethyl-bis(2,2'-bipyridine) ruthenium(II)) 1,4,7,10-tetraazacyclododecane, a macrocyclic sensor for positively charged species. AB - The luminescent behavior of the cyclen-based macrocycle L1 was investigated to establish its sensing ability for protons and transition metal ions. It acts as a good pH sensor in the neutral region. Its interaction with Cu (II) and Ni (II) is accompanied by quenching. The rate data for the interaction with Cu (II) were measured at pH 7.43. PMID- 11774842 TI - An improved metabolic calibrator for stress test equipment: protocol for its clinical utilization. AB - In previous articles, the technical specifications, validation and clinical applicability of a new metabolic calibrator for stress test apparatuses were described. However no indication was given of a basic protocol for the current clinical practice. Here we present an organised check system to satisfy this aim. A method for the exhaustive evaluation of the technical reliability of the metabolic instruments is presented together with the proposal of a uniform simulation approach to organise checks on-line of the apparatuses' ability to follow correctly the various test phases (protocol). Examples of recordings of checks using the standardised approach are shown. The method seems to be very effective. Every operation is computer directed. PMID- 11774843 TI - Comparative in vitro activity of isepamicin and other antibiotics against gram negative bacilli from intensive care units (ICU) in Belgium. AB - The in vitro activity of isepamicin was compared to that of amikacin, gentamicin, cefepime, ciprofloxacin and meropenem against Gram-negative bacilli isolated from patients hospitalized in the intensive care unit (ICU) of 11 Belgian university or general hospitals between November 1998 and July 1999. The minimal inhibitory concentrations (MIC) for 1087 non-duplicate, consecutive aerobic Gram-negative isolates, including 798 Enterobacteriaceae and 289 non-fermenters, were determined by E-test for each antibiotic. Overall, isepamicin was active against 91% of all isolates and was found more active than ciprofloxacin (84% susceptibility), gentamicin (88% susceptibility), cefepime and amikacin (89% susceptibility each), but less active than meropenem (94% susceptibility). Enterobacter aerogenes isolates exhibited the highest resistance rate to ciprofloxacin (72%) while P. aeruginosa appeared the most resistant (frequently multi-resistant) pathogen. Compared to amikacin, MIC values for isepamicin were usually two- to fourfold lower for most inducible Enterobacteriacieae species and for Klebsiella spp., while they were identical for P. aeruginosa and other non fermenters. Complete cross-susceptibility or cross-resistance between amikacin and isepamicin was observed in more than 95% of all tested isolates. On the other hand, 12% of all E. aerogenes isolates appeared resistant to amikacin and susceptible to isepamicin, while 6% of the P. aeruginosa were found to be resistant (or intermediate) to isepamicin and intermediate (or susceptible) to amikacin. No significant differences in pathogen distribution nor in resistance rates were observed between hospitals except for P. aeruginosa. Taking into account the species distribution and the prevalence of resistance to the different antibiotics tested, isepamicin appears as a suitable agent for empiric therapeutic use in severe ICU-acquired Gram-negative infections in Belgium. PMID- 11774844 TI - [Perineal reconstruction with hidden catgut sutures. 1876]. PMID- 11774845 TI - Elevated serum levels of sFas in acute viral hepatitis. PMID- 11774846 TI - 1,25(OH)2D, the preferred substrate for CYP24. PMID- 11774847 TI - Acetabular defect reconstruction with impacted morsellized bone grafts or TCP/HA particles. A study on the mechanical stability of cemented cups in an artificial acetabulum model. AB - In revision surgery of the acetabulum bone defects can be filled with impacted human morsellized bone grafts. Because of a worldwide limited availability of human bone, alternatives are being considered. In this study we compared the initial stability of acetabular cups after reconstructing a cavitary defect with various compositions of impacted tricalciumphosphate-hydroxyapatite (TCP/HA) particles and mixes of TCP/HA particles and human grafts in a realistic acetabulum model. Primary cemented cups and reconstructions with impacted human cancellous grafts were used as reference. A dynamic load displaced the acetabular cups superomedially. The primary cemented cups showed the highest stability. The cups with impacted human grafts produced the most displacement. All reconstructions with the TCP/HA particles showed a high stability of the cups. However, especially when using large TCP/HA particles this was probably due to a large amount of cement penetration. Mixing TCP/HA particles with human grafts seemed to decrease cement penetration. although still a high stability was obtained. In this perspective, we concluded that TCP/HA particles might be useful as a bone graft extender in the reconstruction of acetabular bone defects. PMID- 11774848 TI - Dental resin composites containing silica-fused whiskers--effects of whisker-to silica ratio on fracture toughness and indentation properties. AB - Dental resin composites need to be strengthened in order to improve their performance in large stress-bearing applications such as crowns and multiple-unit restorations. Recently, silica-fused ceramic whiskers were used to reinforce dental composites, and the whisker-to-silica ratio was found to be a key microstructural parameter that determined the composite strength. The aim of this study was to further investigate the effects of whisker-to-silica ratio on the fracture toughness, elastic modulus, hardness and brittleness of the composite. Silica particles and silicon carbide whiskers were mixed at whisker:silica mass ratios of 0:1, 1:5. 1:2, 1:1, 2:1, 5:1, and 1:0. Each mixture was thermally fused, silanized and combined with a dental resin at a filler mass percentage of 60%. Fracture toughness was measured with a single-edge notched beam method. Elastic modulus and hardness were measured with a nano-indentation system. Whisker:silica ratio had significant effects on composite properties. The composite toughness (mean+/-SD; n = 9) at whisker:silica = 2:1 was (2.47+/-0.28) MPa m(1/2), significantly higher than (1.02+/-0.23) at whisker:silica = 0:1, (1.13+/-0.19) of a prosthetic composite control, and (0.95+/-0.11) of an inlay/onlay composite control (Tukey's at family confidence coefficient = 0.95). Elastic modulus increased monotonically and hardness plateaued with increasing the whisker:silica ratio. Increasing the whisker:silica ratio also decreased the composite brittleness, which became about 1/3 of that of the inlay:onlay control. Electron microscopy revealed relatively flat fracture surfaces for the controls, but much rougher ones for the whisker composites, with fracture steps and whisker pullout contributing to toughness. The whiskers appeared to be well-bonded with the matrix, probably due to the fused silica producing rough whisker surfaces. Reinforcement with silica-fused whiskers resulted in novel dental composites that possessed fracture toughness two times higher than, and brittleness less than half of current dental composites. PMID- 11774849 TI - An in vitro investigation of plasma sprayed hydroxyapatite (HA) coatings produced with flame-spheroidized feedstock. AB - The in vitro behaviour and characteristics of plasma sprayed hydroxyapatite (HA) coatings using flame-spheroidized HA feedstock powder on titanium alloy (Ti-6Al 4V) substrates were investigated in a simulated physiological environment as an attempt to reflect the actual incubational condition of an implant in a human body system. As-sprayed and heat-treated HA coatings were immersed in a simulated body fluid with ionic concentrations comparable to that of human blood plasma for time intervals 2, 4, 6, 8 and 10 weeks. Rapid dissolution of calcium phosphate was found to occur within the first 4 weeks, and after the 5th week a retarding rate of 4.1 mM week(-1) was observed where precipitation, nucleation, and, growth of a carbonate-containing, poorly crystallized or amorphous calcium phosphate layer on the as-sprayed coatings were noted. The heat-treated coatings showed minimal or no precipitation on the surface except for the presence of calcite minerals that is due to carbonation effect. Complete dissolution of other calcium phosphate phases such as tetracalcium phosphate, tricalcium phosphate and calcium oxide was also noted after 2 weeks of immersion due to higher ionic solubility relative to HA. A declining trend in respective microhardness and elastic modulus of the as-sprayed HA coatings from 207.06 +/- 3.2 H(k300) to 131.8 +/- 5.2 H(k300) and from 31.37 +/- 1.4 to 19.81 +/- 1.6 GPa was observed after 10 weeks of immersion. Tensile bond strength of both types of coatings showed similar declining trend, with an average dip from 24.5 +/- 2.4 to 7.9 +/- 2.6 MPa. Nevertheless. the heat-treated samples showed rather reasonable mechanical stability and structural integrity of 26.7 +/-1.4 GPa in elastic modulus after soaking. PMID- 11774850 TI - Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. AB - This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly(L-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1 x 10(4) and 1 x 10(6) SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons mm2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a "bioactive" nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation. PMID- 11774851 TI - Multi-layered microcapsules for cell encapsulation. AB - Mechanical stability, complete encapsulation, selective permeability, and suitable extra-cellular microenvironment, are the major considerations in designing microcapsules for cell encapsulation. We have developed four types of multi-layered microcapsules that allow selective optimization of these parameters. Primary hepatocytes were used as model cells to test these different microcapsule configurations. Type-1 microcapsules with an average diameter of 400 microm were formed by complexing modified collagen with a ter-polymer shell of 2 hydroxyethyl methylacrylate (HEMA), methacrylic acid (MAA) and methyl methacrylate (MMA), resulting in a capsule thickness of 2-5 microm. Cells in these microcapsules exhibited improved cellular functions over those cultured on collagen monolayers. Type-II microcapsules were formed by encapsulating the Type I microcapsules in another 2-5 microm ter-polymer shell and a approximately 5 microm collagen layer between the two ter-polymer shells to ensure complete cell encapsulation. Type-II microcapsules comprised of a macro-porous exoskeleton with materials such as alumina sol-gel coated on the Type-I microcapsules. Nano indendation assay indicated an improved mechanical stability over the Type-I microcapsules. Type-IV microcapsules were created by encapsulating Type-III microcapsules in another 2-5 microm ter-polymer shell, with the aim of imparting a negatively charged smooth surface to minimize plasma protein absorption and ensure complete cell encapsulation. The permeability for nutrient exchange, cellular functions in terms of urea production and mechanical stability of the microcapsules were characterized. The advantages and limitations of these microcapsules for tissue engineering are discussed. PMID- 11774852 TI - Stability of radiopaque iodine-containing biomaterials. AB - Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials. PMID- 11774853 TI - Crack growth resistance of alumina, zirconia and zirconia toughened alumina ceramics for joint prostheses. AB - Mono-phase bio-ceramics (alumina and zirconia) are widely used as femoral heads in total hip replacements (THR) as an alternative to metal devices. Unfortunately, the orthopaedic community reports significant in-vivo failures. Material scientists are already familiar with composites like alumina zirconia. Since both are biocompatible, this could prove to be a new approach to implants. This paper deals with a new generation of alumina-zirconia nano-composites having a high resistance to crack propagation, and as a consequence may offer the option to improve lifetime and reliability of ceramic joint prostheses. The reliability of the above mentioned three bio-ceramics (alumina, zirconia and zirconia toughened alumina) for THR components is analysed based on the study of their slow crack-growth behaviour. The influence of the processing conditions on the microstructure development, of the zirconia toughened alumina composites and the effect of these microstructures, on its mechanical properties, are discussed. PMID- 11774854 TI - Experimental studies on a new bioactive material: HAIonomer cements. AB - The lack of exotherm during setting, absence of monomer and improved release of incorporated therapeutic agents has resulted in the development of glass ionomer cements (GICs) for biomedical applications. In order to improve biocompatibility and biomechanically match GICs to bone, hydroxyapatite-ionomer (HAIonomer) hybrid cements were developed. Ultra-fine hydroxyapatite (HA) powders were produced using a new induction spraying technique that utilizes a radio-frequency source to spheriodize an atomized suspension containing HA crystallites. The spheriodized particulates were then held at 800 degrees C for 4 h in a carbolite furnace using a heating and cooling rate of 25 degrees C/min to obtain almost fully crystalline HA powders. The heat-treated particles were characterized and introduced into a commercial glass ionomer cement. 4 (H4), 12 (H12) and 28 (H28) vol% of fluoroalumino silicate were substituted by crystalline HA particles that were dispersed using a high-speed dispersion technique. The HAIonomer cements were subjected to hardness, compressive and diametral tensile strength testing based upon BS6039:1981. The storage time were extended to one week to investigate the effects of cement maturation on mechanical properties. Commercially available capsulated GIC (GC) and GIC at maximum powder:liquid ratio (GM) served as comparisons. Results were analyzed using factorial ANOVA/Scheffe's post-hoc tests and independent samples t-test at significance level 0.05. The effect of time on hardness was material dependent. With the exception of H12, a significant increase in hardness was observed for all materials at one week. A significant increase in compressive strength was, however, observed for H12 over time. At 1 day and 1 week, the hardness of H28 was significantly lower than for GM, H4, and H12. No significant difference in compression and diametral tensile strengths were observed between materials at both time intervals. Results show that HAIonomers is a promising material, which possess good mechanical properties. Potential uses of this new material include bone cements and performed implants for hard tissue replacement in the field of otological, oral-maxillofacial and orthopedic surgery. PMID- 11774855 TI - Seasonal variation in 1/f fluctuations of heart rate in asthmatic children. AB - We have reported previously that asthmatic children have a seasonal variation in the power spectrum in the low frequency, LF (0.04-0.15 Hz) and high frequency, HF (0.15-0.6 Hz) bands of heart rate variability (HRV). In recent years, the l/f fluctuations of heart rate (HR) have been used as a novel index of autonomic function from a chronobiological viewpoint. As asthma is a disease with symptoms affected by seasonal chronobiological changes, we examined whether the l/f fluctuations of HR in asthmatic children changed by season. The subjects examined were 87 asthmatic and 104 healthy children. Using a Holter recorder, a 24-h ambulatory electrocardiogram (AECG) was obtained from each subject. The l/f fluctuations of HR during the time awake, the time asleep, and the 24-h period for each of the four seasons were analyzed by the MemCalc system (Suwa Trust). No seasonal variations of HR l/f fluctuations were detected in either the asthmatic or the control group for any of the three periods analyzed. There was a significant seasonal variation in the mean of the normal-to-normal R-R intervals during the 24-h period in the asthmatic children, but not in the healthy children. In the children with asthma, although their HR varied by season, the l/f fluctuations of HR did not. PMID- 11774857 TI - Changes in ultra-low and very low frequency heart rate variability after coronary artery bypass grafting. AB - This study was performed to assess the effects of coronary artery bypass grafting (CABG) on the ultra-low (ULF) and very low (VLF) frequency components of heart rate variability (HRV). Forty-nine CABG patients (aged from 38 to 77 years) were examined by 24-h ambulatory electrocardiographic (AECG) monitoring, both preoperatively and 4 weeks after CABG. HRV spectral components were obtained by maximum entropy method analysis. Then the ULF, VLF, low frequency (LF), high frequency (HF) and total frequency (TF) components were compared before and after CABG. The average 24-h heart rate increased significantly after CABG (69+/-11.5 vs 82.9+/-10.9 beats per minute [bpm], P < 0.0001). The power of the ULF, VLF, and LF spectral components showed a decrease after surgery (2,859.9 vs 1,601.2 ms2, P<0.0001, 1,215.0 vs 572.3 ms2, P<0.0001, and 260.3 vs 125.9 ms2, P< 0.002, respectively), but the HF power did not show any significant change (98.7 vs 125.9 ms2, NS). Analysis of the normalized ratio of the ULF component (ULF/TF ratio) revealed a significant increase postoperatively (0.6496+/-0.0931 vs 0.7003+/-0.1338, P < 0.0001), but the VLF/TF and LF/TF ratios decreased after CABG (from 0.2671+/-0.0689 to 0.2040+/-0.0832, P< 0.0001 and from 0.0568+/-0.0290 to 0.0429+/-0.0232, P< 0.0088, respectively). In contrast, there was no significant alteration in the HF/TF ratio. These results suggest that recovery of cardiac autonomic activity is delayed after surgery. However, improvement of the ULF/TF ratio, one of the prognostic indicators for patients with cardiac disease, should be related to the relief of myocardial ischemia by CABG. PMID- 11774856 TI - Secular and seasonal cycling of IA2-ab autoantibody in Slovak diabetic children. AB - The concept of seasonal and secular cycling of initial autoantibody plasma levels in children with diabetes mellitus 1 is not common, despite the known fluctuations in one of the triggering factors, i.e., various enteroviral infections. The aim of this study was therefore to assess the trends and cycles in the time series of IA2-autoantibody (ab) blood plasma levels measured in each patient at the moment of diagnosis of the disease, before the first injection of insulin. In a retrospective study, the IA2-ab data, with each item related to a calendar day, were analyzed from 83 male and 108 female patients aged up to 14 years, with the date of disease menifestation between January 1993 and December 1999. The data source was the Slovak National Register of Childhood Diabetes. The plasma levels of the autoantibody against pancreatic tyrosine phosphatase (IA2 ab) were measured by radioimmunoassay. The chronogram of the daily observed values, modified by moving averages, from three successive data items per patient, was processed by Halberg's cosinor method to test the presence of seven year sinusoids and one-year rhythms. One seven-year sinusoid, peaking in February 1998 (boys) and in October 1996 (girls), and a seasonal rhythm culminating in May/June each year were significant. There are some similarities to the cycling of other variables such as the incidence of diabetes, the birth of future diabetics, Coxsackie virus epidemics and pancreatic glutamic acid decarboxylase (GAD 65) autoantibody. Moreover, some cosmo-geophysical periods also seem to be cycling in a parallel manner. The novelty of this contribution is that it examines the seasonal cycling of the autoantibody, connected with the pathogenesis of diabetes and directed against IA2-ab. PMID- 11774858 TI - Can nutrition influence circadian rhythm and heart rate variability? AB - Recent studies indicate that there is an interaction between biorhythms, the biological clock and triggers, which may be important in the pathogenesis of altered heart rate variability (HRV) and blood pressure variability (BPV). Circadian rhythms are under the influence of, and physiological variables are mediated by the activation of the adrenals, sympathetic/parasympathetic, hypothalamic and pituitary activity. Emotional stress, physical exertion, sleep deprivation and large fatty meals are major triggers of myocardial ischemia, angina, infarction, sudden cardiac death (SCD) and stroke. These events have been reported to exhibit a circadian variation with increased frequency in the second quarter of the day, which has also been observed in our studies on Indians. Recent studies indicate that altered HRV and BPV are also important in the pathogenesis and progression of heart failure, atheroma and thrombosis. Mediation via beta-blockers, oestrogens, n-3 fatty acids, vitamin E and coenzyme Q10 and fasting appears to have a beneficial influence whereas progestins, nifedipine, stress and exercise may have an adverse effect on HRV and BPV. We have reported that plasma levels of vitamin E and C are lower in the second quarter of the day than at other times, indicating their role in the pathogenesis of variability and cardiac events. Prospective studies also indicate that HRV and BPV are important and independent risk factors for cardiovascular events. However, no study has yet been conducted in patients with abnormal HRV and BPV in a randomized, placebo controlled intervention trial to find out whether improvement in variability can cause a significant reduction in cardiovascular events. There is a need to study the role of n-3 fatty acids, coenzyme Q10, the effect of regular physical training, medication and ACE inhibitors in patients with abnormal HRV and BPV to demonstrate that improving variability can modulate cardiovascular events. PMID- 11774859 TI - Impact of circadian amplitude and chronotherapy: relevance to prevention and treatment of stroke. AB - The long-acting calcium antagonist nifedipine reduces the incidence of stroke in Eastern Asia, as shown by the Shanghai Trial Of Nifedipine in the Elderly (STONE) and the Systolic Hypertension in China (Syst-China) trials. Recent trials in Japan have shown that benidipine may be more efficient than the former drug in preventing strokes in the elderly. Benidipine, commonly prescribed in Japan for a definite depressor effect, reportedly without causing remarkable fluctuations in blood pressure (BP), is investigated herein from a chronobiological viewpoint. Eighteen subjects (nine women and nine men, 39 to 87 years of age) with essential hypertension (office and ambulatory systolic, S/diastolic, D BP values above 160/95 mm Hg and 130/80 mm Hg, respectively) were enrolled in this investigation. Ambulatory BP was monitored at 30-min intervals for at least 24 h (ABPM-630, Colin Medical) before and after 4 weeks of crossover treatment with nifedipine tablets (twice daily, 20 mg/d) and benidipine (once daily, 4 mg/d, in the morning). The results indicate that: 1) benidipine and nifedipine reduce 24-h daytime (10:00-20:00) and nighttime (00:00-06:00) averages of SBP and DBP (P < 0.001); 2) the circadian double amplitude of BP is decreased after treatment with benidipine (from 28.6 to 21.1 mm Hg SBP and from 19.7 to 15.2 mm Hg DBP; P< 0.05), while the day-night difference in SBP is increased after treatment with nifedipine (18.6 vs 27.9 mm Hg, P< 0.01); and 3) the increase in the day-night difference of heart rate (HR) is significant after treatment with benidipine (13.6 vs 18.8 beats per minute, bpm; P< 0.05), but not with nifedipine. We have previously evaluated the usefulness of the circadian amplitude of BP as a prognostic tool of cardiovascular outcome, and found that an excessive circadian SBP or DBP amplitude was associated with an increased risk of vascular disease. The fact that benidipine reduces the circadian BP amplitude may be one reason for the superiority of this treatment over nifedipine in preventing an adverse outcome. A reduced heart rate variability (HRV) also predicts adverse cardiovascular outcomes in patients with overt cardiovascular disease and in hypertensive subjects. The fact that benidipine increases the day-night difference in HR may be another reason for the positive effects of this treatment. PMID- 11774860 TI - Correlation between timing of surgery in relation to the menstrual cycle and prognosis of premenopausal breast cancer patients. AB - The timing of surgery in relation to menstrual phase might affect the progress of disease in premenopausal women with operable breast cancer. In the present study, the records were examined of 28 such cases treated between 1990 and 1999, and compared for recurrence-free survival with reference to the phases of the menstrual cycle defined by Hrushesky and Senie. During the follow-up period, breast cancer relapse occurred in five patients, and one patient died of another disease unconnected with recurrent breast cancer. The recurrence rate was not significantly different between two phases classified by either Hrushesky or Senie. However, patients with early-stage breast cancer operated during the perimenstrual phase and those with advanced breast cancer which was resected during the peri-ovulatory phase appeared to have a better prognosis than patients operated on during the other phases. Since the prognosis for breast cancer patients is dependent not only on the menstrual cycle but also on many other factors, it is concluded that the menstrual cycle cannot constitute an absolute prognostic factor. PMID- 11774861 TI - Intragastric acidity and circadian rhythm. AB - Most patients with peptic ulcers or gastroesophageal reflex disease develop subjective symptoms of epigastralgia and retrosternal pain during the period of time from the middle of the night to the early dawn (nocturnal pain). Such pain often disappears before breakfast. Disturbed circadian rhythm of gastric acid secretion may have a close relationship with the onset and aggravation of acid related diseases. On the other hand, Helicobacter pylori has been considered to be an etiological agent of duodenal ulcer, and H. pylori eradication has been conducted in patients with gastritis and peptic ulcers. However, such eradication therapy sometimes results in the onset or deterioration of gastroesophageal reflux diseases. In this context, the question of whether the circadian rhythm of gastric acid secretion varies in accordance with the presence or absence of H. pylori infection is of interest. In the present study, we examined the fluctuation in intragastric acidity via a portable pH meter in 10 H. pylori positive and 10 H. pylori-negative subjects. As a result, a significant difference in the circadian rhythmicity was observed between the H. pylori negative and the H. pylori-positive group, with mean values for each parameter of 28.1 and 13.3 for amplitude, 22.7 and 12.4 for the midline-estimating statistic of rhythm (MESOR), and 324.0 and 321.0 for acrophase, respectively (P < 0.001). In both H. pylori-positive and negative groups, a tendency was observed toward an increase in intragastric acidity during the time period from the middle of the night to the early dawn, and toward a decrease in intragastric acidity during the early morning. In the H. pylori-positive group, the values for intragastric acidity over time were lower, and the degree of amplitude was smaller as compared to the H. pylori-negative group. Further, H. pylori-positive individuals were at a more advanced stage of the disease. PMID- 11774862 TI - Theophylline chronotherapy of nocturnal asthma using bathyphase of circadian rhythm in peak expiratory flow rate. AB - We studied the efficacy of theophylline chronotherapy for nocturnal asthma using the changes of the circadian rhythms in peak expiratory flow rate (PEF). Eight patients with nocturnal asthma were evaluated for the periods with nocturnal symptoms and with an evening dose of theophylline administered daily. Patients recorded their PEF every 4 hours on one of the days (from 7:00 to 23:00 h) in each period. Circadian rhythms in PEF were examined using the single and group mean cosinor method. Significant circadian rhythms in PEF were observed in the period with nocturnal symptoms. When nocturnal symptoms were present, the bathyphase of PEF was present between midnight and morning. A significant circadian rhythm disappeared or PEF amplitude decreased during theophylline chronotherapy. The circadian rhythm in PEF was altered according to the severity of the asthma. In patients with symptoms present between midnight and early morning, an evening dose of theophylline chronotherapy can be prophylactically used for nocturnal asthma attacks. Consideration of the circadian rhythm and bathyphase of PEF is useful in selecting appropriate chronotherapy for nocturnal asthma. PMID- 11774863 TI - Fluctuations of Emax of the left ventricle: effect of atrial natriuretic polypeptide. AB - Recently the circadian rhythm of fluctuations in heart rate variability (HRV) has gained increasing attention, and the use of appropriate treatment corresponding to the circadian rhythm has become an important issue. However, the question has been raised as to whether the rhythm of fluctuation is only limited to HRV, and if a rhythm is also present in the contraction of the heart. The mathematical technique of electrical circuit simulation of the cardiovascular system was used to observe the Emax rhythm. In this study, the therapeutic effect of various drugs, including atrial natriuretic polypeptide (ANP), was confirmed. The effect of inotropic drugs including ANP on Emax was observed, and the results based on an old and a new method of determining Emax . were examined. Furthermore, the chaos analysis of Emax was also made. The time series of Emax showed an increased complexity due to the administration of ANP. In conclusion, it might be important to consider not only the fluctuation of HRV, but also an analysis of the fluctuation in the contraction of the heart. PMID- 11774864 TI - Chronomics. AB - Several international meetings have revealed an accumulating body of reference values for well-established about-daily and about-yearly rhythms of photic origin and evidence also for about-7-day, -27-day, -half-yearly, -10.5- and -21-yearly, and even -50-yearly rhythmicities in us as well as around us, as invisible non photic heliogeophysical signatures possibly built into individuals and/or populations, complementing the biological year and day. In time series (biological or other) that are dense and sufficiently long, the characteristics of rhythms, chaos (deterministic and other) and trends can all be quantified as elements of structures called chronomes. Chronobiological methodology assesses uncertainties in comparisons of endpoints in all elements of chronomes, before and after: 1) changes in lifestyle, such as meal quality, quantity, timing and salting of the food; 2) preventive non-drug interventions to limit the risk of vascular disease; or 3) drug treatments for high-risk subjects as well as for those with actual vascular disease, all on a practicable, individualized and also a general population basis. A collateral hierarchy characterizes molecular to psychosocial aspects of living beings that are exposed to their socio-ecological environs and thus are synchronizable and/or otherwise manipulable by society, meals, lighting, heating, and non-photic, non-thermic environmental variations that become predictable to the extent that they appear to constitute cycles, yet adhere only to a statistical, rather than a deterministic causality. With this qualification, chronome mapping with outcomes could eventually serve an individualized optimization of lifestyle, for chronoprevention and chronotherapy as well as for inquiries into the evolution and future of life, a budding chronoastrobiology, in keeping with the original title of the conference. PMID- 11774865 TI - Our life is protected by the Earth's atmosphere and magnetic field: what aurora research tells us. AB - Our sun is an average middle-aged star. Without the sun, there would be no atmosphere, no water, and no life on the Earth. The sun is constantly changing, providing the Earth with energy through a complicated chain of processes that occur in space surrounding the Earth. This paper demonstrates that life on Earth is protected by two barriers, i.e., the atmosphere and the magnetic field, against otherwise menacing events in space. Because of these shielding effects, we, peacefully sitting on the Earth's surface, are not aware of a number of critical and potentially dangerous episodes that are taking place only 100 km above the Earth's surface. The aurora, which dances in the polar sky also because of the two barriers, is sending us a crucial hint about what is happening in space. PMID- 11774866 TI - Space environment, electromagnetic fields, and circadian rhythm. AB - Human space activity began in 1961. About 400 persons have gone to space since then, and about 70 of them have stayed more than 1 month. Circadian rhythm and sleep in space have been investigated several times, though the effect of longer stays in space has not been adequately clarified. Electromagnetic fields are different in the space environment, especially in deeper space missions, such as the Moon or Mars, but their effects on human health have rarely been studied. In this article, we summarize the current status of the International Space Station project, study circadian rhythm and sleep in space, investigate electromagnetic fields, and state the necessity for investigating this research field. PMID- 11774867 TI - The week, inherited in neonatal human twins, found also in geomagnetic pulsations in isolated Antarctica. AB - About 7-day (circaseptan) components, found at different levels of organization, notably in relation to growth, regeneration, repair and development, are often viewed as reflecting no more than the 7-day societal schedule, ample evidence for a built-in feature notwithstanding. Herein, we resolve circaseptans in geomagnetic pulsations recorded by a stand-alone magnetometer residing in Antarctica, far away from societal influences. Human physiological data, collected in the neonatal intensive care unit, show by intra-class correlation analysis that the nonlinearly assessed circaseptan period of heart rate, diastolic blood pressure and body weight is more similar between same-gender twins than among twin pairs, lending additional support for the endogenicity of circaseptans. Like circadians, about-weekly features in environmental variables such as geomagnetic pulsations were genetically acquired in the course of evolution. PMID- 11774868 TI - Geomagnetic disturbance associated with decrease in heart rate variability in a subarctic area. AB - BACKGROUND: Physical environmental variables, such as the natural variation in the geomagnetic field in and around the earth, influence biological processes and human health. The effect of geomagnetic disturbances on heart rate variability (HRV) in healthy students in a subarctic area is studied herein. SUBJECTS AND METHODS: Seven-day records by Holter ECG were obtained from eight clinically healthy subjects in Alta, Norway (70 N). Frequency- and time-domain measures of HRV were compared between 24-hour spans of high geomagnetic disturbance versus quiet conditions. RESULTS: A 5.9% increase in the 24-hour average of HR (P = 0.020) and a 25.2% decrease in HRV (P = 0.002) were documented on days of high geomagnetic disturbance. The decrease in spectral power was found primarily at frequencies lower than 0.04 Hz and was not statistically significant around 3.6 sec. CONCLUSIONS: The physiological mechanism involved may be other than the parasympathetic, usually identified with spectral power centered around 3.6 sec, a spectral region wherein no statistically significant differences were found. PMID- 11774869 TI - Geomagnetic activity influences the melatonin secretion at latitude 70 degrees N. AB - Factors other than light may affect variations in melatonin, including disturbances in the geomagnetic field. Such a possibility was tested in Alta, Norway, located at latitude 70 degrees N, where the aurora borealis is a result of large changes in the horizontal component (H) of the geomagnetic field. Geomagnetic disturbances are felt more strongly closer to the pole than at lower latitudes. Also noteworthy in Alta is the fact that the sun does not rise above the horizon for several weeks during the winter. To examine whether changes in geomagnetic activity influence the secretion of melatonin, saliva was collected from 25 healthy subjects in Alta several times during the day-night and at different times of the year. Single cosinor analyses yielded individual estimates of.the circadian amplitude and MESOR of melatonin. A 3-hour mean value for the local geomagnetic activity index, K, was used for approximately the same 24-hour span. A circadian rhythm was found to characterize both melatonin and K, the peak in K (23:24) preceding that of melatonin (06:08). During the span of investigation, a circannual variation also characterized both variables. Correlation analyses suggest that changes in geomagnetic activity had to be of a certain magnitude to affect the circadian amplitude of melatonin. If large enough (> 80 nT/3 h), changes in geomagnetic activity also significantly decreased salivary melatonin concentration. PMID- 11774870 TI - Alternating light-darkness-influenced human electrocardiographic magnetoreception in association with geomagnetic pulsations. AB - Geomagnetic variations of partly interplanetary origin, with cyclic signatures in human affairs and pathology include the incidence of various diseases, regarding which this study of healthy subjects attempted to determine an underlying mechanism by worldwide archival and physiological monitoring, notably of heart rate variability (HRV). In the past half-century, the possible health and other hazards of natural, solar variability-driven temporal variations in the earth's magnetic field have become a controversial subject in view of the inconsistent results. Some well-documented claims of associations between geomagnetic storms and myocardial infarction or stroke have been rejected by a study based on more comprehensive data analyzed by rigorous methods - covering, however, only part of a solar cycle in only part of a hemisphere. It seems possible that inter-solar cycle and geographic variability, if not geographic differences, may account for discrepancies. Herein, we examine the start of a planetary study on any influence of geomagnetic disturbances that are most pronounced in the auroral oval, on human HRV. The magnetic field variations exhibit complex spectra and include the frequency band between 0.001-10 Hz, which is regarded as ultra-low frequency by physicists. Since the 'ultra-low-frequency' range, like other endpoints used in cardiology, refers to much higher frequencies than the about-yearly changes that are here shown to play a role in environmental-organismic interactions revealed by HRV, the current designations used in cardiology are all placed in quotation marks to indicate the need for possible revision. Whether or not this suggestion has an immediate response, we have pointed to a need for the development of instrumentation and software that renders the assessment of circadian, infradian and even infra-annual (truly low frequency) modulations routinely feasible. HRV was examined on the basis of nearly continuous 7-day records by ECG between December 10, 1998, and November 2, 2000, on 19 clinically healthy subjects, 21 to 54 years of age, in Alta, Norway. A geomagnetic record was obtained from the Auroral Observatory of the University of Tromso. First, frequency-domain measures of HRV were compared for each person in 24-hour spans of high geomagnetic disturbance versus quiet conditions. Second, cross-spectra between geomagnetic activity and HRV measures were quantified via the squared coherence spectrum using 7-day time series. A 7.5% increase in the 24-hour average of heart rate, HR (P = 0.00020) and a decrease in HRV were documented on days of high geomagnetic disturbance. The decrease in HRV was validated statistically for the 'total frequency', 'TF' endpoint (18.6% decrease, P= 0.00009). The decrease in spectral power was found primarily in the 'circaminutan frequency', 'VLF' (21.9% decrease, P< 0.000001) in conjunction with the 'minutes-to-hours' component, ultra-low frequency, 'ULF' (15.5% decrease, P= 0.00865) and circadecasecundan 'low frequency', 'LF' (14.2% decrease, P = 0.00187) regions of the spectrum. Power-law scaling of the power spectra did not show any statistically significant difference. It is noteworthy that most of the decrease in HRV, except for the circaminutan (VLF) component, was observed only in the season in which sunshine alternated with darkness (D/L), a finding suggesting a mechanism influenced by the alternation of light and darkness. The hypothesis of a light-dark-influenced magnetoreception was also supported by cross-spectral analysis. Group-averaged coherence at frequencies coincident with the geomagnetic Pc 6 pulsations (with periods ranging from 10 minutes to 5 hours) differed with a statistical significance (P < 0.000001) among the three natural lighting conditions, the association being weaker during UL or D/D than during D/L. By contrast, no statistically significant differences were found in terms of the circadian and circasemidian frequencies in relation to the alternation of sunshine with darkness or rather circannual rhythm stage. In conclusion, evidence is provided herein that an alteration of HRV is most apparent in the circaminutan ('VLF') region, which is clinically important, because a reduction in its power is a predictor of morbidity and mortality from cardiovascular disease. The circadecasecundan ('LF') component of HRV also decreased in association with geomagnetic disturbance, which may reflect an episodic alteration of arterial pressure related to changes in geomagnetic activity. Lastly, our study suggests the existence of a light-dark-influenced magnetoreception mechanism in humans involving mainly the Pc 6 band of the magnetic field. PMID- 11774871 TI - Associations by signatures and coherences between the human circulation and helio and geomagnetic activity. AB - Helio-geomagnetic influences on the human circulation are investigated on the basis of an 11-year-long record from a clinically healthy cardiologist, 35 years of age at the start of monitoring. He measured his blood pressure and heart rate around the clock with an ambulatory monitor programmed to inflate an arm cuff, mostly at intervals of 15-30 minutes, with only few interruptions, starting in August 1987. While monitoring is continuing, data collected up to July 1998 are analyzed herein by cosinor rhythmometry and cross-spectral coherence with matching records of solar activity, gauged by Wolf numbers (WN) and of the geomagnetic disturbance index, Kp. A direct association between heart rate (HR) and WN is found to be solar cycle stage-dependent, whereas an inverse relationship between heart rate variability (HRV) and WN is found consistently. An inverse relation is also observed between WN and the variability in systolic blood pressure (SBP), and to a lesser extent, diastolic blood pressure (DBP). Moreover, HR is cross-spectrally coherent with WN at a frequency of one cycle in about 7.33 months. The results support previously reported associations on morbidity and mortality statistics, extending their scope to human physiology monitored longitudinally. PMID- 11774872 TI - Circadian rhythms and clinical chronobiology. PMID- 11774873 TI - Infradian, notably circaseptan testable feedsidewards among chronomes of the ECG and air temperature and pressure. AB - To study the interactions among the natural physical environmental cycles and human infradian components of heart rate (HR) and HR variability (HRV), a healthy 49-year-old man in Kiev, who had monitored his electrocardiogram (ECG) around the clock earlier for 50 days, added at a later date with the same ambulatorily wearable device, a record of 70 days. The mean value of the R-R intervals (R-R), their standard deviation (SDNN) and other HRV endpoints, computed over consecutive 5-min intervals, served as markers of the subject's functional associations with the amplitude of fluctuations in atmospheric pressure (FAP) and the planetary Kp index of geomagnetic disturbance. About-weekly and half-weekly cycles in HRV endpoints indicate a reduction in physiological 'preparedness', here described as 'dynamics', of the subject investigated on Saturdays and Sundays and a sharp increase in 'dynamics' on Mondays. The waveform of the weekly oscillation seemed to be influenced by ambient air temperature and FAP. On Mondays, an FAP amplification or a temperature rise was accompanied by a significant decrease in R-R and SDNN, indicating an aggravation of a 'Monday effect' in physiological 'dynamics'. HRV endpoints also revealed about-5-day and about-12-day cyclic components similar to those found in FAP. The infradian pattern in a 70-day record differed from one found earlier in a 50-day record of the same subject. Changes in the natural physical environment (past as well as present), especially in air temperature and FAP, likely influence(d) if not synchronize(d) the amplitude and waveform of infradian weekly and half-weekly physiological cycles. Some of these infradians, their wobbly nature notwithstanding, may have been built into our temporal make-up by an evolutionary integration of life in the non-stationary quasi-periodic natural physical environment, which continues to contribute to variability. PMID- 11774874 TI - Circadian and infradian rhythms in mood. AB - The aim of this study was to assess any variation in positive, negative and total affect recorded longitudinally; to compare the results with those from prior transverse or hybrid population studies, based on the same or a different method of mood rating; and to test for any association of mood with cardiovascular, hormonal and geophysical variables monitored concomitantly. The study approach was as follows. A clinically healthy 34-year-old man filled out the positive and negative affective scale (PANAS) questionnaire five times a day for 86 days. Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) were also measured automatically at 30-minute intervals with an ambulatory monitor from May 19 to June 29, 2000, while different endpoints of heart rate variability (HRV) were also determined at 5-minute intervals from beat-to-beat electrocardiogram (ECG) monitoring for 42 days between May 3 and June 14, 2000, with only short interruptions while the subject took a shower and changed ECG tapes. Saliva samples were collected at the times of mood ratings for one month for later determination of melatonin and cortisol concentrations. Intervals of 24 hours of the record of each variable displaced in increments of 24 hours were analyzed by chronobiologic serial section at a trial period of 24 hours to assess the circadian characteristics as they changed from one day to another. Estimates of the midline-estimating statistic of rhythm (MESOR) and circadian amplitude and acrophase obtained on consecutive days were correlated among variables to assess any associations. The findings were as follows. Overall, a circadian rhythm was demonstrated for all variables. A positive association was noteworthy between the circadian amplitude of negative affect and the MESOR of both SBP (r= 0.363; P= 0.029) and DBP (r= 0.389; P= 0.019), suggesting that BP is raised in the presence of large swings in negative affect. Needing further validation was a weak association between the MESOR of negative affect and the circadian amplitude of SBP (r= - 0.272; P = 0.108), suggesting a lowering of the circadian SBP amplitude in the presence of a strong negative affect. Of further interest was the lack of a statistically significant relation between positive and negative affect, not only in terms of the MESOR but also in terms of the circadian amplitude. PMID- 11774875 TI - Annulus senilis. PMID- 11774876 TI - Editor's comment on: "Press release: further research supports Viagra safety profile". PMID- 11774877 TI - Comparative architecture of transposase and integrase complexes. AB - Transposases and retroviral integrases promote the movement of DNA segments to new locations within and between genomes. These recombinases function as multimeric protein-DNA complexes. Recent success in solving the crystal structure of a Tn5 transposase--DNA complex provides the first detailed structural information about a member of the transposase/integrase superfamily in its active, DNA-bound state. Here, we summarize the reactions catalyzed by transposases and integrases and review the Tn5 transposase-DNA co-crystal structure. The insights gained from the Tn5 structure and other available structures are considered together with biochemical and genetic data to discuss features that are likely to prove common to the catalytic complexes used by members of this important protein family. PMID- 11774878 TI - Editor's comment. Press release: further research supports Viagra safety profile. PMID- 11774879 TI - [A botanist in the Holy Land]. PMID- 11774880 TI - [Martin Pollich von Mellrichstadt (b. 1455-d. 1513) and his dispute with Simon Pistoris on the origin of "syphilis"]. PMID- 11774882 TI - Perceptions of physical restraint use and barriers to restraint reduction in a long-term care facility. AB - The use of restraints in nursing homes has been curtailed in the United States since the passage of the 1987 federal legislation regulating restraint practices. This study used focus groups with administrators and nursing staff in a skilled nursing facility to examine their views of restraints and perceptions of conditions in the nursing home environment that affect restraint use. Although respondents lacked a shared definition of a "restraint," they did identify contextual factors that in combination with resident characteristics produced situations in which restraint use was justified. Implications of these findings for staff education on restraint reduction are discussed. PMID- 11774883 TI - Museums on paper in Emilia-Romagna from the sixteenth to the nineteenth centuries: from Aldrovandi to Count Sanvitale. AB - Ever since the Middle Ages, the art of Emilia Romagna (a region of Italy), and more generally of the Po Valley, has been characterised by great attention to aspects of daily life. This particular situation has undoubtedly encouraged the relations and links between the world of art and that of science. And, indeed, in Emila Romagna throughout the modern age a large number of painters worked on commission for naturalists and an equally large number of scientists and 'amateurs' themselves undertook the illustration of nature, or were interested in the problems and techniques of the figurative arts, or collected objects d'art. PMID- 11774881 TI - The oldest old; autonomy in the face of frailty. AB - Autonomy, a core American value, is routinely invoked as a goal in gerontological discussions of the aging process, yet frailty, another commonly used term in gerontology, suggests that functional losses may interfere with individuals' ability to maintain autonomy in everyday life. Older persons who are impaired are seldom asked how they view themselves with respect to autonomy and frailty, or what autonomy means. The meanings older persons attach to autonomy and decreases in physical abilities are explored through in-depth interviews with 28 persons age 80 or older. While autonomy encompassed a wide range of self-descriptions, respondents never used the word, frail, to describe themselves. I explore the potential of the construct of the lived body for a holistic approach to aging that values embodied knowledge and experiences of those who are old. I conclude that gerontological views of autonomy promote a cultural ideal that does not reflect elders' perspectives, and that the notion of frailty has the potential to stereotype elders, with negative effects on well being. PMID- 11774884 TI - The study of the natural sciences and botanical and zoological illustration in Tuscany under the Medicis from the sixteenth to the eighteenth centuries. AB - A vast body of botanical and zoological illustrations was produced in Tuscany between the sixteenth and the eighteenth century. This artistic activity was made possible by the humanistic-scientific tradition which had been established in Florence during the late fifteenth century, and was further encouraged by the Medici dynasty. The contributions made by three uniquely talented and original artists are discussed. Jacopo Ligozzi produced paintings of plants and animals whose scientific accuracy and artistic quality far surpassed anything achieved by his predecessors. The miniaturist Giovanna Garzoni produced floral paintings for the Medici family. Bartolomeo Bimbi combined the genre of botanical and zoological illustration with that of the still life to create works of striking originality. The crucial role played by the new scientific institutions created during the Renaissance is also discussed. A permanent artists' studio was set up in the mid-sixteenth century at Pisa Botanic Garden. Members of Accademia del Cimento in Florence engaged in pioneering studies with the microscope, a newly invented instrument which gave scientists and artists an entirely new perspective on the natural world. The scientist Francesco Redi carried out important work with the help of the artist Filizio Pizzichi who prepared stunning microscopic studies of insects. PMID- 11774885 TI - Patrick Browne M. D. (c. 1720-1790), an Irish doctor in the Caribbean: his residence on Saint Croix (1757-1765) and his unpublished accounts of volcanic activity on Montserrat. AB - Patrick Browne resided on the Caribbean islands of Saint Croix (a Danish possession) and Montserrat (an English possession) during the 1750s and 1760s. He collected and recorded the flora of Saint Croix; some of his notes about the plants of the island have survived and are transcribed. On Montserrat he made observations on the active volcano; the surviving manuscript accounts of the sulphur-rich springs are transcribed. PMID- 11774886 TI - Measurement of the people by the people, and for the people. PMID- 11774887 TI - From cutting nature and its joints to measuring it: new kinds and new kinds of people in biology. AB - In the received version of the development of science, natural kinds are established in the preliminary stages (natural history) and made more precise by measurement (exact science). By examining the move from nineteenth- to twentieth century biology, this paper unpacks the notion of species as 'natural kinds' and grounds for discourse, questioning received notions about both kinds and species. Life sciences in the nineteenth century established several 'monster-barring' techniques to block disputes about the precise definition of species. Counterintuitively, precision and definition brought dispute and disrupted exchange. Thus, any attempt to add precision was doomed to failure. By intervening and measuring, the new experimental biology dislocated the established links between natural kinds and kinds of people and institutions. New kinds were built in new places. They were made to measure from the very start. This paper ends by claiming that there was no long-standing 'species problem' in the history of biology. That problem is a later construction of the 'modern synthesis', well after the disruption of 'kinds' and kinds of people. Only then would definitions and precision matter. A new, non-linguistic, take on the incommensurability thesis is hinted at. PMID- 11774888 TI - The ontology of the questionnaire: Max Weber on measurement and mass investigation. AB - Although contemporary sociologists of science have sometimes claimed Max Weber as a methodological precursor, they have not examined Weber's own writings about science. Between 1908 and 1912 Weber published a series of critical studies of the extension of scientific authority into public life. The most notable of these concerned attempts to implement the experimental psychology or psycho-physics laboratory in factories and other real-world settings. Weber's critique centered on the problem of social measurement. He emphasized the discontinuities between the space of the laboratory and that of the factory, showing how several qualitative and historically conditioned differences between the two settings rendered the transfer of instruments and methods between them highly problematic. Weber's critical arguments prepared the ground for his greatest foray into empirical sociology, a survey he directed for the Verein fur Sozialpolitik investigating the conditions and attitudes affecting the lives and performance of industrial workers. Using a different measuring instrument - the questionnaire - Weber tried to implement a concept of social measurement which implied a different ontology, drawn not from natural sciences but from the historical sciences. PMID- 11774889 TI - Why can't you scientists leave things alone? Science questioned in British films of the post-war period (1945-1970). AB - Considerable attention has been paid to the representation of scientists as villains in horror and science fiction films, and to the part this has played in creating the public perception of scientists. But science and scientists have also been represented in films which do not fit readily with the conventions of these genres, and these "mainstream" films allow a more detailed investigation of the public perception of science at the time they were made. This paper examines a number of British mainstream films portraying scientists and science from the period 1945-1970 to see in what ways the conduct of science was being questioned. A concern with the political control of science and the resulting secrecy is evident in a number of the films. The criticism of scientists seems to come from two contradictory directions. Scientists were either seen as too detached and unconcerned about the consequences of their work, or they were too emotional and insufficiently objective. This is in part explained by newer, less deferential attitudes to science co-existing with the older, heroic view during the period under study. PMID- 11774890 TI - The "Silent Springs" of Rachel Carson: mass media and the origins of modern environmentalism. AB - This essay explores the different meanings of the 1960s' pesticide controversy as conveyed by the multiple representations of Rachel Carsons's Silent Spring (1962). I argue that to understand the impact of Carson's work on a heterogeneous audience in the early '60s, we must move beyond an examination of the book, Silent Spring, to consider its other media manifestations, as a serialization for The New Yorker and as a television expose for "CBS Reports." Each conveyed a unique message stylized for the audience of that particular media. This analysis demonstrates the problems and opportunities for scholars attempting to gauge the influence of a book on the public understanding of science. This argument also suggests that to understand the transition of environmentalism from a grass-roots movement to near universal consensus, we need to examine carefully the role of media in shaping divergent messages for different audiences--a phenomenon that assisted in transforming local environmental issues into a matter of national concern. PMID- 11774891 TI - The making of a Darwinian left. [Review of: Dickens, P. Social Darwinism, 2000; Lewontin, R. The Triple Helix: Gene, Organism, and Environment, 2000; Singer, P. A Darwinian Left: Politics, Evolution and Cooperation, 1999]. PMID- 11774892 TI - Transmission of arboviruses without involvement of arthropod vectors. AB - Transmission of arboviruses (arthropod-borne viruses belonging to various virus families) without involvement of arthropod vectors has been documented for years, but the reports have not been reviewed systematically. The recent report of West Nile (WN) virus isolation from a hawk in mid-winter in New York (Garmendia et al., J. Clin. Microbiol. 38, 3110-3111, 2000) generated a considerable interest in this mode of arbovirus transmission. In this article, the data available worldwide are analyzed according to the factors involved in such a transmission under natural conditions, mode of infection, virus entry mechanism, administration and efficacy evaluation of vaccines, and significance in agricultural trade and public health. Analysis of numerous reports compiled for this review revealed that peroral and intranasal/aerosol transmissions are very common among arboviruses. The mechanism of virus infections in animals was most extensively studied for intranasal/aerosol infection, confirming two routes of virus spread to central nervous system (CNS), olfactory and hematogenous. To rule out the possibility of asymptomatic, cryptic infection the efficacy evaluation of candidates for vaccines against neurotropic arboviruses should include virus isolation from tissues of not only symptomatic but also of asymptomatic animals that survive intranasal virus challenge. Human activities, such as feeding livestock animals with food containing virus-contaminated meat and assembling a large number of livestock from many geographically-separated locations, have been identified as a cause of spread of some arboviral diseases. Despite numerous laboratory reports, the significance of this mode of transmission of arboviruses under natural conditions was rarely investigated, except for a few viruses important for veterinary medicine. PMID- 11774893 TI - Occurrence of graft-transmissible virus diseases of the strawberry in the Czech Republic. AB - Strawberry virus diseases were monitored using a leaf graft bioassay in 17 cultivars of strawberry Fragaria ananassa Duchesne in the Czech Republic. Fragaria vesca indicator clones revealed after grafting several symptoms of strawberry mottle, crinkle, vein banding, and mild yellow edge as well as of mixed virus infections. Isometric virus-like particles (VLPs) ranging from 21 to 50 nm in diameter and flexuous filamentous VLPs (12 by 600-1400 nm) were observed by electron microscopy in negatively stained crude sap preparations. Our results confirmed the complexity of virus diseases of the strawberry and represent the first report on the detection of strawberry mild yellow edge disease (SMYED) and of filamentous particles in this crop in the Czech Republic. PMID- 11774894 TI - Sequence analysis of recent Indian isolates of foot-and-mouth disease virus serotypes O, A and Asia 1 from clinical materials. AB - Partial nucleotide sequences of 1D gene of 38 isolates of foot-and-mouth disease virus (FMDV) of serotypes O, A and Asia 1 originating from various parts of India were determined. Field materials were subjected straight to RNA extraction, reverse transcription - PCR (RT-PCR) and sequencing. Also 3 FMDV vaccine strains, IND R2/75 (serotype O), IND 63/72 (serotype Asia 1) and IND 17/77 (serotype A) were included in the analysis. The seqences were compared mutually as well as with available corresponding sequences of other FMDV isolates, and their phylogenetic relationships were calculated. The deduced amino acid sequences showed that the serotype O isolates were relatively conserved as compared to serotype Asia 1 or A isolates from India. In phylogenetic analysis, the serotype O viruses clustered in two genotypes, one including the European vaccine strain (O1/K) and the other represented by the isolates from Bangladesh, India, Nepal and Turkey. The serotype Asia 1 viruses clustered in two groups of single genotype where the prototype strain from Pakistan (PAK 1/54) formed one group and the other was formed by the isolates from Bangladesh, Bhutan, India, Israel and Nepal. In serotype A viruses three well-differentiated genotypes were observed. The isolates from Azerbaijan, Bangladesh, Malaysia and India formed the first genotype. The second genotype was formed by isolates from Iran, Saudi Arabia and Turkey, while two recent Iranian isolates represented the third genotype. In India, the prevalence of at least one genotype could be identified in each serotype. This evolutionary clustering of isolates from the neighbor countries is not surprising, since these countries share border with India. The genetic relatedness between sequences of isolates from India and those from distant places is indicative of spread of the virus between the countries. Of importance is the fact that clinical materials proved useful for rapid generation of sequences and subsequent studying of molecular epidemiology of the disease. PMID- 11774895 TI - Comparison of virus isolation and polymerase chain reaction for diagnosis of peste des petits ruminants. AB - Oculonasal swabs and tissue samples collected from peste des petits ruminants (PPR) suspected sheep and goats were tested for presence of the virus of peste des petits ruminants (PPRV) or its RNA by reverse transcription-PCR (RT-PCR) and virus isolation (VI). Of 44 samples 31.8% and 40.9% were positive by VI and RT PCR, respectively. The RT-PCR-positive samples were subjected to the nested PCR. Three of six samples positive by RT-PCR but negative by VI were negative by the nested PCR. The specificity and accuracy of the nested PCR were higher than those of the RT-PCR although the sensitivity of both tests were similar. Nucleotide sequencing of one nested PCR product revealed a 92% homology with the sequence available in the GenBank (Acc. No. Z37017). PMID- 11774896 TI - Isolation and evaluation of Coxiella burnetii O-polysaccharide antigen as an immunodiagnostic reagent. AB - A lipid A - deprived lipopolysaccharide (LPS) from Coxiella burnetii (C.b.) Priscilla strain in virulent phase I was separated by steric-exclusion chromatography and high performance liquid chromatography (HPLC). The isolated O specific polysaccharide (PS) fractions were analyzed by different physico chemical methods and showed noticeable differences in their overall composition. The antigenic potential of the PS fractions was evaluated by ELISA with animal and human sera and in comparison with those of the native C.b. LPSs and phase I and II C.b. Nine Mile stain cells of which the latter are routinely used in diagnosis of Q fever. The results indicate that the high molecular mass PS antigen SG501 could be used in ELISA for a sensitive and specific detection of anti-C.b. antibodies in the examined sera. PMID- 11774897 TI - Virus-inhibitory effect of a yeast RNA-tilorone molecular complex in cell cultures. AB - The virus-inhibitory activity of a molecular complex (MC) of tilorone and yeast RNA was studied in vitro on three virus-cell systems: vesicular stomatitis virus (VSV) - murine fibroblast L929 cells, Venezuelan equine encephalittis virus (VEEV) - swine embryo kidney (SEK) cells and encephalomyocarditis virus (EMCV) - established piglet testicular (EPT) cells. In all these systems the MC exerted an antiviral effect similar to that of polynucleotide interferon (IFN) inducers such as poly(I)-poly(C), larifan and ridostin. The antiviral effect of the MC was similar when the compound was applied before or after virus adsorption to cells. The MC may be regarded as a perspective antiviral agent of common use. PMID- 11774898 TI - Human cytomegalovirus UL21.5 gene is expressed as an "early-late" gene in cultured human fibroblasts. AB - The human cytomegalovirus (CMV) UL21.5 gene encodes a secreted glycoprotein of unknown function. Both the UL21.5 protein and mRNA accumulate in abundance at late stages of infection making the RNA an attractive target for diagnosis of active CMV infection. The UL21.5 was originally described as a 'spliced late' gene (SLG) (Rawlinson and Barrell, J. Virol. 67, 5502 (1993)). However, we found that the the UL21.5 mRNA was detectable in CMV-infected patients before the onset of CMV DNA replication (Boriskin et al., J. Clin. Virol., in press). Here, we re examined the UL21.5 mRNA kinetic class in CMV-infected human fibroblast culture using a RNAse protection assay and RT-PCR. The UL21.5 mRNA was detectable before the "true late" UL75 RNA, was resistant to a CMV DNA replication inhibitor but moderately sensitive to inhibitors of protein synthesis. In the presence of protein synthesis inhibitors the UL21.5 mRNA was detectable only by a nested reverse transcription - PCR (RT-PCR) with the bulk of it in unspliced form. This suggests that splicing factors for UL21.5 mRNA are encoded by the virus rather than by the cell. Our results indicate that UL21.5 should be defined as an "early late" rather than a "late" (L) CMV gene. PMID- 11774899 TI - The cellular nuclear matrix regulatory protein YY1 does not directly interact with the mouse polyomavirus large tumor antigen. AB - The transcription factor Yin-Yang 1 (YY1) is a multifunctional protein involved in repressing and activating many promoters of cellular and viral genes. YY1 functions via protein-DNA but also protein-protein interactions. The latter has been documented between YY1 and early gene products of adenoviruses (Lewis et al., J. Virol. 69, 1628-1636 (1995)) and papillomaviruses (Lee et al., Virol. 72,4911-4917 (1998)). In this study, first of this kind on mouse polyomavirus (Py), we report that YY1 and the main viral regulatory protein, large tumor antigen (LT), do not interact directly in vivo. This evidence was obtained by use of two separate methods, immunoprecipitation (IP) and a yeast two-hybrid system. PMID- 11774900 TI - Homology of bovine herpesvirus 2 and herpes simplex virus 1 proteins. PMID- 11774901 TI - Reduction of signal suppression effects in ESI-MS using a nanosplitting device. AB - Electrospray ionization mass spectrometry is a valuable tool in the identification and quantification of drug metabolites in biological fluids. However, there are many instances where matrix components present in these fluids interfere with analyte detection and prevent the acquisition of accurate or complete results. In some instances, the matrix can suppress ionization to such an extent that analytes are completely undetectable by MS. In this work, we investigate how ionization and ion-transfer efficiencies are affected by drastically reducing the flow into the MS. A postcolumn concentric flow-splitting device was constructed to allow the measurement of analyte signal and ionization suppression across a range of flow rates (0.1-200 microL/min). Using this device, the effects of flow rate on signal intensity and ionization suppression were measured in analytical experiments that included flow injection analysis MS, postcolumn addition LC-MS, and on-line LC-MS analysis of metabolites generated from rat liver microsomes. The device used to deliver 0.1 microL/min flows is referred to as a nanosplitter because it achieved high split ratios (2000:1), producing flow rates comparable to those observed in nanoelectrospray. The nanosplitter maintained chromatographic integrity with high fidelity and allowed the direct comparison of analyte signal across a range of flow rates (0.1-200 microL/min). A significant improvement in concentration and mass sensitivity as well as a reduction in signal suppression is observed when the performance at 200 versus 0.1 microL/min flow rate is compared. Using this specially designed concentric splitting device, the advantages of ultralow flow ESI were easily exploited for applications employing large bore chromatography. PMID- 11774902 TI - Fabrication of a configurable, single-use microfluidic device. AB - This paper describes microfluidic devices that contain connections that can be opened by the user after fabrication. The devices are fabricated in poly(dimethylsiloxane) (PDMS) and comprise disconnected fluidic channels that are separated by 20 microm of PDMS. Applying voltages above the breakdown voltage of PDMS (21 V/microm) opened pathways between disconnected channels. Fluids could then be pumped through the openings. The voltage used and the ionic strength of the buffer in the channels determined the size of the opening. Opening connections in a specific order provides the means to control complex reactions on the device. A device for ELISA was fabricated to demonstrate the ability to store and deliver fluids on demand. PMID- 11774903 TI - Headspace solvent microextraction. AB - A hanging microliter drop of 1-octanol is shown to be an excellent preconcentration medium for headspace analysis of volatile compounds in an aqueous matrix by gas chromatography (GC) or gas chromatography/mass spectrometry (GC/MS). Model compounds benzene, toluene, ethylbenzene, and o-xylene (BTEX) are conveniently and rapidly preconcentrated in the microdrop. An internal standard, decane, is present in the organic extracting solvent, and linear calibration curves of relative peak area versus aqueous concentration are obtained for the four model compounds. Detailed kinetic studies reveal that the overall rate of mass transfer is limited by both the aqueous-phase stirring rate and the degree of convection within the organic phase. The very low vapor pressure of 1-octanol results in minimal evaporation of the microdrop during the extraction time. This system represents an inexpensive, convenient, and precise sample cleanup and preconcentration method for the determination of volatile organic compounds at trace levels. PMID- 11774904 TI - Liquid-phase microextraction of phenolic compounds combined with on-line preconcentration by field-amplified sample injection at low pH in micellar electrokinetic chromatography. AB - This paper describes a novel method that applies field-amplified sample injection (FASI) in micellar electrokinetic chromatography (MEKC) with a low pH background electrolyte (BGE). Six phenolic compounds prepared in water or NaOH solution were used as the test analytes. Sample was injected electrokinetically after the introduction of a plug of water. During the injection, the water plug was pumped out of the capillary inlet by the electroosmotic flow, and the phenolic anions migrated very quickly in the direction of the outlet. When the anions reached the boundary between the water plug and BGE, they were neutralized and ceased moving. Thereafter, MEKC was initiated for the separation. This on-line preconcentration method could be conveniently coupled with a liquid-liquid-liquid microextraction procedure, in which a hollow fiber was used as an extraction solvent support to extract the analytes from the water sample. The acceptor phase consisted of 8 mM NaOH. After extraction, the extract was analyzed directly by MEKC, as described. PMID- 11774905 TI - Flow fractionation of microparticles under a dielectrophoretic field in a quadrupole electrode capillary. AB - A technique of fractionation for microparticles was proposed that utilized a unique combination of a dielectrophoretic (DEP) field generated by a quadrupole electrode and a laminar flow in a capillary of 82.5 microm in radius. The fabricated capillary possessed four platinum wires in its inside wall as a quadrupole electrode. In a nonuniform electric field generated by the quadrupole electrode, microparticles, such as polystyrene and carbon, in water experienced DEP forces in the radial direction. When a sample solution was pumped in, an ideal laminar flow perpendicular to the DEP force was formed inside the capillary. The microparticles dynamically migrated by the DEP force across the laminar flow while they were carried by the flow. A theoretical model taking the DEP force and the laminar flow pattern into account predicted the elution profiles of the single microparticles quantitatively. The elution times of the microparticles depended on the dielectric properties and the sizes of the microparticles, as well as the voltage and frequency of the applied alternating current. PMID- 11774906 TI - Monitoring polycyclic aromatic hydrocarbon metabolites in human urine: extraction and purification with a sol-gel glass immunosorbent. AB - A new, rapid method for selective extraction of hydroxylated polycyclic aromatic hydrocarbons metabolites (OH-PAHs) in human urine was developed using an immunosorbent of anti-pyrene antibodies which were encapsulated in a sol-gel glass (SGG) matrix. Resulting chromatograms after immunoextraction of urine samples and HPLC analysis of the extracts were free from matrix interferences. The LODs for the determination of OH-PAHs in these difficult samples were in the low-ppt range (1-16 ng/L). In addition to its high selectivity, the immunosorbent proved to be robust and reusable. Obtained recoveries in spiked urine samples ranged from 83 to 107% for the hydroxyphenanthrene and hydroxypyrene compounds under investigation, while recovery for 3-hydroxybenzo[a]pyrene was only 45-62%. In a biomonitoring study, the SGG immunosorbent was successfully used for trace level analysis of OH-PAHs in 20 human urine samples. Results were compared to data obtained by an independent reference analysis method and revealed good correlation between both methods. PMID- 11774907 TI - Two-dimensional gas chromatography and trilinear partial least squares for the quantitative analysis of aromatic and naphthene content in naphtha. AB - Quantitative analysis of naphtha samples is demonstrated using comprehensive two dimensional gas chromatography (GC x GC) and chemometrics. This work is aimed at providing a GC system for the quantitative and qualitative analysis of complex process streams for process monitoring and control. The high-speed GC x GC analysis of naphtha is accomplished through short GC columns, high carrier gas velocities, and partial chromatographic peak resolution followed by multivariate quantitative analysis. Six min GC x GC separations are analyzed with trilinear partial least squares (tri-PLS) to predict the aromatic and naphthene (cycloalkanes) content of naphtha samples. The 6-min GC x GC separation time is over 16 times faster than a single-GC-column standard method in which a single column separation resolves the aromatic and naphthene compounds in naphtha and predicts the aromatic and naphthene percent concentrations through addition of the resolved signals. Acceptable quantitative precision is provided by GC x GC/tri-PLS. PMID- 11774908 TI - An automated multidimensional protein identification technology for shotgun proteomics. AB - We describe an automated method for shotgun proteomics named multidimensional protein identification technology (MudPIT), which combines multidimensional liquid chromatography with electrospray ionization tandem mass spectrometry. The multidimensional liquid chromatography method integrates a strong cation-exchange (SCX) resin and reversed-phase resin in a biphasic column. We detail the improvements over a system described by Link et al. (Link, A. J.; Eng, J.; Schieltz, D. M.; Carmack, E.; Mize, G. J.; Morris, D. R.; Garvik, B. M.; Yates, J. R., III. Nat. Biotechnol. 1999, 17, 676-682) that separates and acquires tandem mass spectra for thousands of peptides. Peptides elute off the SCX phase by increasing pI, and elution off the SCX material is evenly distributed across an analysis. In addition, we describe the chromatographic benchmarks of MudPIT. MudPIT was reproducible within 0.5% between two analyses. Furthermore, a dynamic range of 10000 to 1 between the most abundant and least abundant proteins/peptides in a complex peptide mixture has been demonstrated. By improving sample preparation along with separations, the method improves the overall analysis of proteomes by identifying proteins of all functional and physical classes. PMID- 11774909 TI - An integrated ten-pump, eight-channel parallel LC/MS system for automated high throughput analysis of proteins. AB - An integrated 10-pump eight-channel LC/MS system has been developed for automated high-throughput analysis of intact proteins in recombinant protein purification processes. The key features of the system include (1) a compact 10-pump HPLC module that uses two pumps to generate a binary gradient and 8 pumps to deliver the mixed gradient to eight independent flow channels; (2) a TOF mass spectrometer with an eight-channel multiplexed ESI interface, which records separate data for all eight channels over each HPLC run cycle; and (3) highly automated data processing software that allows unattended calculation of protein molecular weight (in Da) from original mass spectral data (in m/z). This system was used in the routine screening of fractions from preparative scale chromatography to monitor the purification process with the required mass accuracy and throughput. As an example, the production and purification of an acylated protein with a molecular weight of 9 kDa is described. Using this off line approach, it is practical to fully characterize protein-containing fractions from column chromatography with an overall analytical throughput of 1 min/protein sample with minimum operator involvement. PMID- 11774910 TI - Response mechanisms of thermionic detectors with enhanced nitrogen selectivity. AB - The response mechanisms of a thermionic detector with enhanced nitrogen selectivity operating in an inert gas environment were investigated. According to accepted theory, the analyte has to contain electronegative functional groups in order for negative ions to be formed by the extraction of electrons from the thermionic source. This leads to a selective detector response for compounds containing nitro groups or multiple halogens. However, in the tests described here, polycyclic aromatic nitrogen hydrocarbons (PANHs), acridines, and carbazoles were used as reference substances. These compounds contain no electronegative functional groups. None of the investigated acridines exhibited any response from the detector, but carbazoles generated a strong structure related detector response. By examining partial charges for all hydrogens of all individual carbazoles and acridine, it was demonstrated that the acidic hydrogen atom attached to the nitrogen heteroatom of the carbazoles has a strong influence on the detector response. Ionization of carbazoles may occur by dissociation of the nitrogen-hydrogen bond during contact with the thermionic surface. Support for this theory was provided by the linear relationship between the relative detector response and the deprotonization energy of the carbazoles (coefficients of determination of 0.90 and 0.98 for linear and quadratic models, respectively, were obtained). Further, there appeared to be no linear relationship between the detector response and electron affinity of the carbazoles, (R2 value, 0.32). Thus, the mechanism involved in ionization of the carbazoles is probably not direct electron transfer from the thermionic surface to the carbazoles. Principal component analysis (PCA) showed that the thermal conductivity of chemically inert detector gases also has an influence on the detector response. The investigated gases were helium, neon, nitrogen, carbon dioxide, and argon. It was found that thermal conductivity can be used to rank the detector response for the carbazoles, and there was no discernible response when helium, which has the highest thermal conductivity, was used as the detector gas. PMID- 11774911 TI - Modeling of the separation of the enantiomers of 1-phenyl-1-propanol on cellulose tribenzoate. AB - The competitive adsorption isotherms of rac-1-phenyl-1-propanol on cellulose tribenzoate were measured by competitive frontal analysis. The experimental data were fitted to four different isotherm models: Langmuir, Bilangmuir, Langmuir Freundlich, and Toth. The fittings of the experimental data to all four models were satisfactory. It was excellent in the case of the Langmuir-Freundlich and the Toth models. Overloaded elution profiles calculated with the Toth isotherm were in good agreement with the experimental profiles in all the different experimental conditions investigated. This work extends to the case of binary mixtures the equivalence between the general rate and the lumped pore diffusion models already demonstrated for pure compounds when the ratio between the Stanton and the Biot numbers exceeds 5. The adsorption energy distribution for the Toth isotherm was also calculated. PMID- 11774912 TI - Fluorometric field instrument for continuous measurement of atmospheric hydrogen sulfide. AB - A sensitive (limit of detection approximately <100 pptv at S/N = 3), fully automated, portable (32 x 25 x 38 cm, 4.5 kg) instrument has been designed for continuous field measurement of atmospheric hydrogen sulfide. Air is sampled by a PTFE membrane-based diffusion scrubber and collected into an aLkaline fluorescein mercuric acetate (FMA) solution flowing under a controlled and constant pneumatic pressure. The collected sulfide quenches the fluorescence that is measured with a miniature blue LED photodiode-based fluorescence detector. Acquisition and interpretation of signal and all flow control are carried out via a mininotebook personal computer (PC) using custom software written in HP-VEE. The instrument provides for self-calibration and zero functions using an on-board permeation tube enclosed in a thermostated block, at any preprogrammed desired interval. During sampling, the computed H2S concentration is stored every 2 min. The complete system, including the PC, is operated in the field by a 12-V marine battery. The system was field tested near oil field operations in West Texas and showed good correlations with a concurrently operated lead acetate tape-based commercial sampler, with a response speed and time resolution much better than that of the latter instrument. PMID- 11774913 TI - Tandem mass spectrometry of intact proteins for characterization of biomarkers from Bacillus cereus T spores. AB - Intact protein biomarkers from Bacillus cereus T spores have been analyzed by high-resolution tandem Fourier transform ion cyclotron resonance mass spectrometry. Two techniques have been applied for excitation of the isolated multiply charged precursor ion species: sustained off-resonance irradiation/collisionally activated dissociation and electron capture dissociation. Fragmentation-derived sequence tags and BLAST sequence similarity proteome database searches allow unequivocal identification of the major biomarker protein with unprecedented specificity. Sequence-specific fragmentation patterns further confirm protein identification. Moreover, methodology combining accurate mass measurements of intact proteins with additional information contained in a proteome database permits tentative assignment of several other protein biomarkers isolated from the B. cereus T spores. We argue that approaches involving tandem MS of protein biomarkers, combined with bioinformatics, can drastically improve the specificity of individual microorganism identification, particularly in complex environments. PMID- 11774914 TI - Using receptor conformational change to detect low molecular weight analytes by surface plasmon resonance. AB - Small molecules are difficult to directly detect using commercially available surface plasmon resonance (SPR) instruments. This is because low molecular weight compounds do not have sufficient mass to cause a measurable change in refractive index. Refractive index is sensitive, however, to other properties besides the mass of the analyte. Recently the detection of substantial conformational changes for immobilized proteins using SPR has been reported. However, this property has not yet been exploited for the detection of low molecular weight ligand binding to immobilized protein receptors. Here we demonstrate that ligand-induced conformational changes can be used to monitor the binding of small molecules to immobilized maltose-binding protein and tissue transglutaminase. Ligand binding to a receptor that decreases in hydrodynamic radius yielded a net decrease in refractive index. A net positive change in refractive index was observed for a receptor that increases in hydrodynamic radius. Refractive index changes could not be explained by addition of analyte molecular mass to the surface. These SPR responses were a result of specific receptor-ligand interactions, as judged by the reversibility of the response and the similarities between the SPR-determined equilibrium dissociation constants and reported dissociation constants. Additionally, this technique proved to be effective at detecting specific ligands from a panel of small molecules. This SPR method required no alterations in widely used and commercially available instrumentation yet allowed direct detection of very small molecules such as calcium ions (40 Da). Use of receptor conformation to detect low molecular weight analytes has potential applications in the high-throughput screening of small molecule drug libraries and the development of biosensors. PMID- 11774915 TI - Amperometric determination of acetic acid with a trienzyme/poly(dimethylsiloxane) bilayer-based sensor. AB - A trienzyme sensor for the amperometric determination of acetic acid was prepared by immobilizing acetate kinase (AK), pyruvate kinase (PK), and pyruvate oxidase (PyOx) on a poly(dimethylsiloxane) (PDMS)-coated electrode. AK catalyzes the phospho-transferring reaction between acetic acid and ATP to form ADP; PK, the phospho-transferring reaction between ADP and phosphoenolpyruvate to form pyruvic acid; and PyOx, the oxidation of pyruvic acid with oxygen. The oxygen consumption could be monitored by using the PDMS-coated electrode without interference from the PyOx reaction product, hydrogen peroxide. Thus, the concentration of acetic acid (5 microM-0.5 mM) could be determined from the decrease in the cathodic current at -0.4 V vs Ag/AgCl. This is the first example of a biosensor that can be used for the determination of acetic acid in ethanol-containing food samples. The acetate-sensing electrode could be used for more than one month. PMID- 11774916 TI - Spectroscopic investigations of poly(propyleneimine)dendrimers using the solvatochromic probe phenol blue and comparisons to poly(amidoamine) dendrimers. AB - The physical and chemical properties of PPI dendrimers' interior were investigated using the fluorescent, solvatochromic probe phenol blue. In aqueous solutions of each generation studied, two discrete dye populations were clearly observed. PPI dendrimers were shown to form a tight, nonpolar association with the vast majority of available dye, within the dendrimer interior, near the core. In the steady-state fluorescence emission spectra, a microenvironment of decreasing polarity in increasingly larger-generation PPI dendrimers (up to G3) was seen for the associated probe. Each of the remaining larger-generation dendrimers provided a microenvironment of essentially equal polarity. Fluorescence anisotropy values for phenol blue in the PPI dendrimers demonstrated the dye's sensitivity to the changing molecular volumes of the dendrimer generations. Model compounds that mimicked PPI's surface groups and branching moieties were used to better define the associated dye's location. The mimics further confirmed that phenol blue was associated inside the dendrimer, where it did not interact with the dendrimer surface groups. The comparison of amine terminated PPI and PAMAM dendrimers clearly demonstrated the effects of their structural differences and the ability of phenol blue to have sensed those differences, including the initiator core length, branching unit length, and branching unit chemical composition. PMID- 11774917 TI - Molecular aptamer for real-time oncoprotein platelet-derived growth factor monitoring by fluorescence anisotropy. AB - Monitoring proteins in real time and in homogeneous solution has always been a difficult task. We have applied a fluorophore-labeled molecular probe based on a high-affinity platelet-derived growth factor (PDGF) aptamer for the ultrasensitive detection of PDGF in homogeneous solutions. The aptamer is labeled with fluorescein to specifically bind with the PDGF protein. Fluorescence anisotropy is used for the real-time monitoring of the binding between the aptamer and the protein. When the labeled aptamer is bound with its target protein, the rotational motion of the fluorophore attached to the complex becomes much slower because of an increased molecular weight after binding, resulting in a significant fluorescence anisotropy change. Using the anisotropy change, we are able to detect the binding events between the aptamer and the protein in real time and in homogeneous solutions (detection without separation). This assay is highly selective and ultrasensitive. It can detect PDGF in the subnanomolar range. The new method for protein detection is simple and inherits all of the advantages of molecular aptamers. Efficient oncoprotein detection using aptamer based fluorescence anisotropy measurement will find wide applications in protein monitoring, in cancer diagnosis as well as other studies in which protein analysis is important. PMID- 11774918 TI - Purification of molecularly bridged metal nanoparticle arrays by centrifugation and size exclusion chromatography. AB - Size exclusion chromatography and centrifugation separation protocols were developed and compared for isolating enriched fractions of phenylethynyl-bridged metal nanoparticle dimers and trimers from the monomeric particle starting material. Both methods enabled the isolation of enriched fractions of a desired array without causing significant sample aggregation or replacement of the phenylethynyl bridge. Solutions containing ca. 70% bridged gold dimers were obtained using either method. The further development of methods for separating discrete arrays of covalently bridged nanoparticle homo and hetero structures is expected to help advance our understanding of collective metal particle electronic structure-function relationships. PMID- 11774919 TI - Laser-induced multidimensional fluorescence spectroscopy in Shpol'skii matrixes with a fiber-optic probe at liquid helium temperature. AB - Improved methodology for chemical analysis via laser-excited Shpol'skii spectrometry at liquid helium temperature (4.2 K) is reported. Sample freezing is performed in a matter of seconds with the aid of a fiber-optic probe directly inserted into the liquid cryogen. Emission wavelength time matrixes, excitation emission wavelengths, and time-resolved excitation emission wavelengths are rapidly collected with the aid of a pulsed tunable dye laser, a high-resolution spectrograph, and an intensified charged-couple device. Data reproducibility for qualitative and quantitative analysis purposes and analytical figures of merit are demonstrated for several polycilic aromatic hydrocarbons/n-alkane systems. Fluorescence lifetime differences from analyte molecules occupying different crystallographic sites in the same frozen matrix are presented for the first time. The potential of our approach is illustrated for the direct analysis of a benzopyrene fraction typically encountered in HPLC analysis of polycyclic aromatic hydrocarbons. PMID- 11774921 TI - Nanoscience and analytical chemistry. PMID- 11774920 TI - Measurement of single-cell gene expression using capillary electrophoresis. AB - Capillary electrophoresis with laser-induced fluorescence detection was used to monitor gene expression in individual mammalian cells using the reverse transcriptasepolymerase chain reaction. Specifically, beta-actin expression in single LNCaP (prostate cancer) cells was measured. A sieving matrix containing hydroxypropyl methyl cellulose was used to effect size-based separation. Ethidium bromide fluorescence of the product DNA was used as the detection scheme and yielded excellent sensitivity. The beta-actin product, resulting from an individual cell lysed by a freeze-thaw method, gave an average signal-to-noise ratio (S/N) of 77+/-27 (n = 2). Chemical lysis of a single cell, using a dilute solution of SDS, gave a S/N of 26+/-2 (n = 2), roughly 3-fold lower than for freeze-thaw lysis. An initial detection limit (not considering fully optimized conditions) was calculated from an amplified cDNA standard to correspond to a concentration of approximately 133 starting molecules/nL (of beta-actin mRNA). PMID- 11774922 TI - Tasty plastic beats glass. PMID- 11774923 TI - Beyond the cellular "cookbook". PMID- 11774924 TI - Great ideas of a decade. PMID- 11774925 TI - Charge transfer reactions at the liquid/liquid interface. PMID- 11774926 TI - Ohio crime solvers. PMID- 11774927 TI - The sound of compounds. PMID- 11774928 TI - Endoscopic ultrasound and pancreatic cysts: a sticky situation! PMID- 11774929 TI - Cholesterol crystal embolization: more common than we thought? PMID- 11774930 TI - What happened to drug trials in ulcerative colitis? Problems, PPARs, placebos, and (possible) progress. PMID- 11774931 TI - Diagnosis of celiac sprue. AB - Celiac sprue is a common lifelong disorder affecting 0.3-1% of the Western world and causing considerable ill health and increased mortality, particularly from lymphoma and other malignancies. Although high prevalence rates have been reported in Western Europe, celiac sprue remains a rare diagnosis in North America. Whether celiac sprue is truly rare among North Americans or is simply underdiagnosed is unclear, although serological screening of healthy American blood donors suggests that a large number of American celiacs go undiagnosed. Celiac sprue is an elusive diagnosis, and often its only clue is the presence of iron or folate deficiency anemia or extraintestinal manifestations, such as osteoporosis, infertility, and neurological disturbances. The challenge for gastroenterologists and other physicians is to identify the large population of undiagnosed patients that probably exists in the community and offer them treatment with a gluten-free diet that will restore the great majority to full health and prevent the development of complications. The advent of highly sensitive and specific antiendomysium and tissue transglutaminase serological tests has modified our current approach to diagnosis and made fecal fat and D xylose absorption testing obsolete. A single small bowel biopsy that demonstrates histological findings compatible with celiac sprue followed by a favorable clinical and serological response to gluten-free diet is now considered sufficient to definitely confirm the diagnosis. We review the wide spectrum of celiac sprue, its variable clinical manifestations, and the current approach to diagnosis. PMID- 11774932 TI - A medical uncertainty principle. AB - Acquisition of diagnostic knowledge and improvement of patient health often are mutually exclusive goals. A perfect understanding of a disease process is only obtained through unrestricted testing that exposes the patient to adverse events and discomfort. In a patient completely undisturbed by test procedures, the physician remains ignorant about the nature of the disease. The interplay of diagnostic knowledge and patient health can be formulated in terms of an uncertainty principle, which allows one to mathematically derive the parameters that influence the balance between the two competing goals. The majority of clinical conditions permit the pursuit of perfect diagnostic knowledge. Occasional medical disasters occur because physicians underestimate the patient's functional reserve or the cumulative toll exerted by multiple tests. Especially in emergency situations or serious illness, the maximum amount of knowledge that can be achieved is far less than perfect. Under such circumstances, the best management option takes into account a "calculated" amount of diagnostic uncertainty. PMID- 11774933 TI - The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults. AB - OBJECTIVE: Sildenafil relaxes smooth muscle by blocking type 5 phosphodiesterase, which destroys nitric oxide-stimulated cyclic guanosine monophosphate. The aim of this study is to investigate the change of lower esophageal sphincter (LES) and body motility with the lapse of time after sildenafil infusion in normal male adults. METHODS: After basal esophageal manometry in eight healthy male adult volunteers, we infused a 50-mg tablet of sildenafil dissolved in water in the stomach through the manometry catheter and observed the changes of LES and body motility with the lapse of time. We randomized the study population into two groups, and esophageal manometry was repeated in LES and body sequence in four volunteers and in body and LES sequence in the other four volunteers immediately after sildenafil infusion. RESULTS: LES resting pressure significantly decreased after sildenafil infusion. The body peristaltic amplitude gradually decreased and eventually disappeared, and the latency increased significantly after sildenafil infusion in both the proximal and distal esophagus. CONCLUSIONS: These data support that nitric oxide mediates LES relaxation and the timing of esophageal peristalsis. In the future, sildenafil can be tried in some esophageal motor disorders, which have defects in nitric oxide neuromuscular communication. PMID- 11774934 TI - Detection of incomplete lower esophageal sphincter relaxation with conventional point-pressure sensors. AB - OBJECTIVE: Completeness of lower esophageal sphincter relaxation, a parameter used to establish the diagnosis of achalasia, is an important manometric determination. This study compared four analysis methods that use point-pressure measurements to determine their relative accuracy and the best threshold values for incomplete relaxation. METHODS: Analyses were performed on 153 manometric studies that employed a 21-lumen catheter with pressure recording sites spaced at 1-cm intervals. Lower sphincter relaxation was measured from most appropriate sites as the 1) lowest residual pressure within 5 s of swallowing, 2) lowest residual pressure across the entire postdeglutitive period, 3) lowest mean residual pressure over a floating 3-s interval after swallowing, and 4) mean transsphincteric esophagogastric gradient extracted from a combination of conventional and topographic manometric information. Intragastric baseline pressures were taken both from the pull-through maneuver and from concurrent intragastric recordings, and methods were compared by their receiver operating characteristics. RESULTS: Best threshold values for segregating achalasia from nonachalasic controls differed across methods and depended on presence or absence of peristalsis in the comparison group. Transsphincteric gradient measurement had high sensitivity (> or = 0.94) and specificity (> or = 0.98) for achalasia irrespective of comparison group and was superior to all other methods. The 3-s mean residual pressure demonstrated greatest discriminant capabilities of the remaining conventional methods, which were modestly improved with concurrent measurement of intragastric pressure. CONCLUSIONS: Analyses that average postdeglutitive pressures are superior to isolated nadir values in correctly discerning incomplete lower sphincter relaxation. The transsphincteric gradient is a novel approach for measuring sphincter relaxation, is unaffected by sphincter asymmetry and axial movement, and has the best receiver operating characteristics using point-pressure sensors. PMID- 11774935 TI - Prospective evaluation of multilayered epithelium in Barrett's esophagus. AB - OBJECTIVE: We recently identified a distinctive type of multilayered epithelium in two patients with Barrett's esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett's esophagus. METHODS: Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells. RESULTS: Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05). CONCLUSIONS: Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett's esophagus. PMID- 11774936 TI - Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger Ellison syndrome. AB - OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine 2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38 67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to control patients, doses > 80 mg b.i.d. may be required. PMID- 11774937 TI - Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection. AB - OBJECTIVE: Our purpose was to find out if morphometric techniques can document long term changes in gastric antral atrophy after curing Helicobacter pylori infection with or without dietary supplementation with antioxidant micronutrients. METHODS: Study subjects were 132 adult volunteers from a Colombian region with high gastric cancer rates. Participants were randomly assigned to ascorbic acid, beta-carotene, and anti-H. pylori treatment, following a factorial design. Gastric biopsies were obtained at baseline and after 72 months of intervention. Atrophy was evaluated by a standard visual analog scale and by morphometry. RESULTS: Statistically significant changes in antral atrophy were detected with morphometric techniques after intervention in subjects who received anti-H. pylori treatment. A nonsignificant trend was also observed with visual scores. This effect was greater among those who were free of infection at the end of the trial. After accounting for the effect of anti-H. pylori treatment, no significant effect was noted for dietary supplementation with ascorbic acid and/or beta-carotene. CONCLUSIONS: We conclude that gastric atrophy improves significantly after long term control of H. pylori infection. This effect can be demonstrated both by conventional histological grading and by morphometry. PMID- 11774938 TI - Helicobacter pylori is not the cause of sudden infant death syndrome (SIDS). AB - OBJECTIVES: The cause of sudden infant death syndrome (SIDS) is unknown, but our previous hypothesis proposed that Helicobacter pylori could be a causative organism. In this study, we aimed to test this hypothesis by examining gastric and tracheal tissues from a prospective cohort of SIDS infants and re-examining previously studied paraffin-fixed tissues for H. pylori. METHODS: Fresh gastric antral and trachea specimens obtained at postmortem from nine consecutive new cases of SIDS in Perth, Western Australia were studied prospectively. Tissues were evaluated for H. pylori by rapid urease test (CLOtest), bacterial culture, histology (hematoxylin and eosin, Warthin-Starry Silver, and immmunoperoxidase staining), and polymerase chain reaction (PCR). The latter two tests were also used for the re-examination of paraffin-embedded specimens from infants who died from SIDS (n = 17) and other non-SIDS causes (n = 7) in Kansas City, Missouri. RESULTS: Specimens from nine consecutive SIDS infants in Western Australia showed no evidence of H. pylori by any analyses. In the paraffin-embedded gastric and trachea specimens from Missouri, rod and coccoid-shaped bacteria were seen histologically in 33.3% of the specimens, but these were not typical H. pylori. Upon analysis by PCR, "H. pylori DNA" was detected in 53% (9/17) of SIDS samples versus 57% (4/7) in non-SIDS samples. In all cases the immunoperoxidase stain was negative, suggesting that PCR either 1) gave false positive results in this type of potentially contaminated postmortem specimen or 2) H. pylori DNA was indeed present but not increased in prevalence in SIDS infants. CONCLUSIONS: H. pylori is unlikely to be an etiological agent in SIDS. PMID- 11774939 TI - Can EUS alone differentiate between malignant and benign cystic lesions of the pancreas? AB - OBJECTIVE: The aim of this study was to evaluate the ability of endoscopic ultrasound (EUS) alone to predict and differentiate malignant from benign cystic lesions of the pancreas. METHODS: From January, 1995, to August, 1999, 98 cases of pancreatic cystic lesions were evaluated by EUS; all of these were originally imaged by cross-sectional modalities that were not diagnostic. Among these, surgical/pathological correlation was available in 48 patients. The original endosonographic images were reviewed by two endosonographers who were blinded to each other's interpretation and to the surgical and pathological interpretation. The EUS images were assessed for the presence or absence of the following characteristics: 1) wall, 2) solid component, 3) septae, 4) lymphadenopathy, and 5) number of cysts. These characteristics were then correlated with the surgical and pathological findings and were assessed to determine if any were predictors of the lesion being benign or malignant. RESULTS: For reviewer A, the presence of a solid component by EUS was the only statistically significant predictor of malignancy (odds ratio = 4.73, 95% CI = 1.13-19.68, p = 0.03). However, 61% of patients with benign lesions were also interpreted by EUS to have a solid component. For reviewer B, none of the features were found to be significant predictors of a malignant lesion. When the results of both reviewers were combined, the presence of a solid component was not found to be a statistically significant predictor of malignancy (odds ratio = 1.046, 95% CI = 0.99-1.09, p = 0.07). CONCLUSION: Endosonographic features cannot reliably differentiate between benign and malignant cystic lesions of the pancreas after a nondiagnostic cross sectional modality. PMID- 11774940 TI - Cholesterol crystal embolization demonstrated on GI biopsy. AB - OBJECTIVES: Cholesterol crystal embolism is a severe complication of atherosclerosis responsible for nonspecific cutaneous, renal, and, less often, digestive manifestations that may mimic other systemic diseases. METHODS: We reviewed retrospectively 10 patients with histologically proven cholesterol crystal emboli diagnosed by endoscopic GI biopsy. RESULTS: All patients had prior clinical manifestations of severe atherosclerosis and predisposing factors for cholesterol migration. They all had cutaneous manifestations of cholesterol crystal embolism, acute renal failure, and biological inflammatory syndrome. Digestive symptoms were found in the 10 patients: abdominal pain in eight, diarrhea in four, and GI bleeding in three. GI endoscopy ruled out specific digestive diseases, showing only a congestive or erosive mucosa. Histological diagnosis of cholesterol crystal emboli was based on gastric biopsy in nine patients, duodenal biopsy in four, colonic biopsy in three, and rectal biopsy in one, with six having positive biopsies on multiple sites. Outcome after the diagnosis of cholesterol crystal embolism was poor, with all patients requiring permanent hemodialysis. Death by atherosclerosis complications occurred in five patients. CONCLUSIONS: This cohort suggests that upper GI endoscopy may be helpful in demonstrating the presence of cholesterol crystal embolism, and that diagnosis of cholesterol crystal emboli on digestive tract biopsy indicates advanced systemic atherosclerosis disease of poor prognosis. PMID- 11774941 TI - Prediction of bile duct stones and complications in gallstone pancreatitis using early laboratory trends. AB - OBJECTIVES: We aimed to determine whether early trends in the serum pancreatic enzymes and liver tests of patients with gallstone pancreatitis predict persistent common bile duct (CBD) stones and complications. METHODS: Medical records of patients with gallstone pancreatitis were reviewed retrospectively. Serial serum pancreatic enzymes and liver tests were recorded until the time of cholangiography. Laboratory trends were analyzed by comparing initial results obtained in the emergency department to subsequent results obtained 8-24 h, 24-48 h, and 48-72 h after presentation. RESULTS: Of 154 patients with gallstone pancreatitis, 28 (18%) had persistent CBD stones at cholangiography. Complications and death were more frequent in patients with persistent CBD stones than in those without CBD stones (29% and 11% vs 12% and 1%, respectively; p < 0.05). Laboratory trends predicted both persistent CBD stones and complications of pancreatitis. When any laboratory value rose between admission and 24-48 h of hospitalization, persistent CBD stones were present in 31% of cases, versus 8% of those in whom all laboratory values remained constant or fell (p = 0.001). Likewise, complications occurred in 21% of those with any rising laboratory value, versus 8% of those in whom all values remained constant or fell (p < 0.05). CONCLUSIONS: Patients with gallstone pancreatitis and rising serum chemistries had a 4-fold risk of persistent CBD stones and a nearly 3-fold risk of complications compared to patients in whom all chemistry values remained constant or fell. This simple prediction rule may identify patients with biliary pancreatitis who are most likely to benefit from early interventions to diagnose and remove persistent CBD stones. PMID- 11774942 TI - Prospective comparison of endoscopy patient satisfaction surveys: e-mail versus standard mail versus telephone. AB - OBJECTIVES: The dramatic growth of the Internet holds potential for use in survey distribution. Comparisons of electronic mail (e-mail) to traditional survey techniques are lacking. We compared standard mail, telephone, and e-mail modes of endoscopy satisfaction survey administration with respect to response rate, timeliness of response, response content, and cost-efficiency of responses. METHODS: An endoscopy satisfaction questionnaire consisting of seven core items from the modified Group Health Association of America-9 survey was distributed to patients after routine outpatient endoscopy. Patients were randomized to receive the questionnaire by standard mail, telephone, or e-mail. Response rates and findings in the three groups were compared. The "nonresponders" to the standard mail and e-mail surveys were subsequently contacted by telephone to determine their level of satisfaction. RESULTS: The phone survey response rate (90%) was higher than e-mail (70%) or standard mail (85%), although e-mail was the most cost-efficient mode of survey delivery. There was no significant difference in satisfaction scores among the three groups. Nonresponders were significantly more satisfied than "responders." CONCLUSIONS: A survey technique utilizing e-mail with subsequent follow-up by telephone to nonresponders appears to be the most cost-efficient way to deliver a questionnaire. The satisfaction levels of the responders may underestimate the overall satisfaction of the population being surveyed. PMID- 11774943 TI - Utility of an upper echoendoscope for endoscopic ultrasonography of malignant and benign conditions of the sigmoid/left colon and the rectum. AB - OBJECTIVE: The majority of data on colonic endoscopic ultrasound (EUS) are limited to malignant lesions in the rectum and diseases of the anal sphincter. The forward-oblique-viewing upper echoendoscope has been mostly applied for staging rectal cancer. A front-viewing echocolonoscope is available but has not been widely used because of limited indications and the expense of buying another instrument. The purpose of our study was to evaluate the utility of a forward oblique-viewing upper echoendoscope for EUS of malignant and benign lesions of the sigmoid/left colon and the rectum. METHODS: Thirty-two EUS exams were performed for a variety of indications in the rectum and the sigmoid/left colon. The patients were prepared for the exam in a manner similar to the performance of flexible sigmoidoscopy. Flexible sigmoidoscopy was performed in all cases before performing EUS. Surgical path data were reviewed in all cases if the patient had surgery after EUS. RESULTS: Twenty-six exams were done for staging of rectosigmoid carcinoma, follow-up after chemotherapy and/or radiation, or to look for recurrence after resection of colorectal cancer. Surgical pathology results were available in 20 patients. The accuracies of EUS were 85% for T staging and 80% for N staging. Six EUS exams were for benign causes, including evaluation for the presence of a perirectal abscess in two (no abscess found), to rule out rectal varices in one (EUS confirmed rectal varices), and evaluation of submucosal lesions. One patient subsequent to EUS imaging also underwent a linear EUS-guided fine-needle aspiration of a submucosal mass in the rectum with the fine-needle aspirate consistent with a myogenic tumor. CONCLUSIONS: The forward oblique-viewing upper echoendoscope is a versatile instrument that can be applied for EUS imaging of malignant and benign indications not only in the rectum but also in the sigmoid/left colon. PMID- 11774944 TI - An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis. AB - OBJECTIVES: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted. PMID- 11774945 TI - Quality of health care in inflammatory bowel disease: development of a reliable questionnaire (QUOTE-IBD) and first results. AB - OBJECTIVES: As inflammatory bowel disease is a chronic disorder, usually with an early onset in life, quality of care plays an important role for patients. The aim of this study was to develop a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease. METHODS: Ten generic questions were already available because the questionnaire is based on an existing instrument. Patients with inflammatory bowel disease in seven countries were involved in the development of additional disease-specific items. Validation and first field testing of the total questionnaire (QUOTE-IBD) was performed in The Netherlands. RESULTS: A total of 380 patients cooperated in the development of 13 disease-specific items, with high internal reliability (Cronbach's alpha = 0.83). Another 162 patients were involved in validating and testing of the QUOTE IBD, which consists of 23 items in total. Pearson's correlation coefficient between QUOTE-IBD and visual analog scale scores of health care items was 0.55. Intraclass correlation coefficient of two assessments was 0.64. First testing showed that patients gave relatively poor marks to some part of health care services, such as providing information about extraintestinal complaints and the psychological as well as physical approach to complaints. CONCLUSIONS: A short, valid, reliable questionnaire was developed to measure the opinions of patients with inflammatory bowel disease on quality of health care. The QUOTE-IBD can be used for identification of areas for improvement, with the aim of optimizing health care in inflammatory bowel disease. PMID- 11774946 TI - The tissue transglutaminase gene is not a primary factor predisposing to celiac disease. AB - OBJECTIVES: The aim of this study was to determine whether the tissue transglutaminase (tTG) gene is a causal factor in the pathogenesis of celiac disease (CD). METHODS: A total of 147 Dutch families with at least one patient with biopsy-proven CD were available for this study. In all patients, CD was diagnosed according to the revised European Society for Pediatric Gastroenterology and Nutrition criteria. A microsatellite marker in a noncoding region of the tTG gene was investigated for both linkage and association. Linkage was tested by determining the amount of allele sharing between affected brothers and sisters (affected sibling [sib] pair analysis). Association was determined by comparing transmission of certain tTG alleles from parents to CD patients to the nontransmitted alleles by the transmission/disequilibrium test. RESULTS: Linkage analysis did not show cosegregation of the tTG gene with celiac disease in our families, and there was no association between certain tTG alleles and celiac disease. Furthermore, the tTG gene could be excluded as a CD susceptibility gene. CONCLUSION: Our results indicate that the tTG gene can be excluded as a major primary genetic factor in CD pathogenesis. PMID- 11774947 TI - Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome. AB - OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B+D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles. PMID- 11774948 TI - Use of pharmaceuticals by inflammatory bowel disease patients: a population-based study. AB - OBJECTIVES: In 1996 we created the population-based University of Manitoba Inflammatory Bowel Disease (IBD) Database. In 1994, Manitoba Health established the Drug Program Information Network (DPIN), which identified all ambulatory prescription drugs dispensed to each individual resident of the province. All residents have a personal health identification number, and use of this number allowed linkage of the IBD database with the DPIN database. Our aim was to use the linkage of these databases to describe prescription drug use by patients with IBD in Manitoba in 1997. METHODS: We analyzed all prescriptions and costs for fiscal year 1997, and stratified our analysis by age, sex, urban versus nonurban residence, income, and disease (Crohn's disease vs ulcerative colitis). We also extracted all subjects diagnosed with IBD in 1984-1987 and those diagnosed in 1994-97 and compared any differences in prescribing patterns in 1997 for these two cohorts. RESULTS: A total of 87.5% of IBD subjects received prescriptions in 1997. There was a direct, significant relationship between increasing age and number of different prescriptions per IBD drug user and total prescription costs per IBD drug user (in adults only), particularly for alimentary drugs. Female patients used a greater number of different prescriptions, but there was no difference between sexes in costs per user. Only 7.8% of patients used immunomodulatory drugs, but these accounted for the greatest cost ($1404) per user. Patients whose disease was diagnosed in 1994-1997 were significantly more likely to be prescribed oral or rectal 5-aminosalicylic acid and steroids than were those whose disease was diagnosed in 1984-1987. In addition, prescriptions for rectal 5-aminosalicylic acid were significantly increased in those patients whose diagnoses were made later over those whose diagnoses were made earlier. Male patients and Crohn's disease patients were more likely to use oral steroids and immunomodulatory medications. Based on the decade of diagnosis, there was no difference in prescribing patterns for immunomodulatory medications. CONCLUSIONS: The linkage of the University of Manitoba IBD Database and the Manitoba DPIN Database allowed a description of patterns of prescription use in a population based sample of IBD patients. Among the important findings are the lack of effect of gender and urban residence on prescription use in IBD patients; however the decade of diagnosis did affect prescribing patterns. Furthermore, only 7.8% overall receive immunomodulatory medications, but this was independent of the decade of diagnosis. PMID- 11774949 TI - Is nausea associated with chronic hepatitis C infection? AB - OBJECTIVES: Hepatitis C virus is a common chronic infection that is widely associated with symptoms of fatigue and pain in the right upper quadrant. Nausea may be an underrecognized symptom. This study was designed to study the frequency of nausea in patients with hepatitis C virus infection compared to controls. METHODS: A cross-sectional study design with consecutive outpatients was used. Three groups were administered a dyspepsia and a previously validated Nausea Profile questionnaire. Univariate and multivariate analysis was performed. RESULTS: A total of 64 hepatitis C virus (HCV) patients, 53 liver disease controls (LC), and 64 normal controls (NC) were studied. An increased period prevalence of nausea was found in HCV patients 43% versus 29.7% in NC and 18.9% in LC (p = 0.009). There was an increased frequency of fatigue and abdominal pain in HCV patients over 1 month compared to LC and NC combined (p = 0.0001 and 0.0065 respectively). The Nausea Profile score revealed statistically higher total scores and higher subscale scores in the HCV group compared to controls. The total NP score expressed as a percentage of the maximum was 27% in HCV versus 12.7% for LC and 9.2% for NC (p = 0.0005). The odds of nausea using logistic regression were 2.1 CI (1.0-4.5) in HCV patients compared to controls (p = 0.05). Using linear regression, higher Nausea Profile scores were found to be independently associated with the diagnosis of HCV (.0005), fatigue (p = 0.0003), and abdominal pain (p = 0.0001). CONCLUSIONS: HCV infection is associated with an increased risk for nausea. The strong association between abdominal pain and nausea may be a clue to the etiology of nausea in these patients. Further etiological studies are needed. PMID- 11774950 TI - Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis. AB - OBJECTIVES: In experimental models, liver injury induced by ethanol, cytotoxic activity of tumor necrosis factor (TNF) -alpha is principally mediated by TNF receptor p55 (TNFRp55). Among the various mechanisms underlying the toxic effects of TNF-alpha, overproduction of reactive oxygen species seems to play a key role in mediating TNF-alpha-induced cytotoxicity. The aim of this study was to evaluate, in patients with alcoholic liver disease, whether alcohol TNFRp55 mediated hepatotoxicity could account for lipid peroxidation expressed by significant increase in serum thiobarbituric reactive acid substances (TBARS) content, and could be amplified by decrease in blood total glutathione content and decrease in plasma antioxidant protective capacity. METHODS: We studied 27 patients with histological alcoholic liver disease (five fibrosis, six acute alcoholic hepatitis (AAH) without cirrhosis, four cirrhosis without AAH, and 12 cirrhosis with AAH. TNFsRp55 and TNFsRp75 plasma levels were measured using ELISA assays. Plasma lipid peroxidation was evaluated by the content of TBARS. Total glutathione (tGSH) content in blood was determined by a kinetic assay. The sensitivity of erythrocytes to an oxidative stress and the plasma antioxidant protective capacity were simultaneously determined by a simple method. RESULTS: In the 18 patients with mild or severe AAH, the plasma levels of TNFsRp55 were negatively correlated with tGSH and were positively correlated with TBARS, with total bilirubin and with discriminant function. tGSH was positively correlated with plasma selenium. The plasma levels of TNFsRp75 were positively correlated with TBARS and with total bilirubin. There was no significant correlation with the mean inhibitory 50% plasma volume or with the percentage of hemolyzed erythrocytes. CONCLUSIONS: Our data support the notions that, in patients with AAH, TNFsRp55 probably mediates cytotoxicity of TNF-alpha, and that cytotoxic effect could be amplified by tGSH depletion in enhancing lipid peroxidation. PMID- 11774951 TI - The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function. AB - OBJECTIVES: Percutaneous transhepatic biliary drainage (PTBD) has been believed to reduce hyperbilirubinemia in patients with obstructive cholestasis and to lessen liver injury through bile acid retention. The efficacy may be closely related to the capability of cholestatic liver to produce and secrete bile, which in turn depends on the expressions and functional activities of plasma membrane transporters in the liver. The aim of the present study was to determine the expression levels of these transporters in the cholestatic liver of patients undergoing PTBD. METHODS: A total of 24 patients who had experienced obstructive cholestasis and had undergone preoperative PTBD were included in the study. Liver biopsy specimens were analyzed to determine the expression levels of the multidrug resistance-associated proteins (MRP) MRP2 and MRP3 and the canalicular bile salt export pump BSEP in the liver. RESULTS: The messenger RNA (mRNA) levels of MRP2, the canalicular bilirubin conjugate export pump, and bile salt export pump (BSEP) were unchanged in liver specimens from the 14 patients well drained by PTBD but were reduced in specimens from the 10 patients poorly drained, compared to the levels of control subjects. Immunostainings of MRP2 and BSEP outlined the canalicular membrane domain but seemed fuzzy to varying degrees in specimens obtained from cholestatic liver, especially in specimens from liver that had been poorly drained, in contrast to the linear and intense localization in the liver of control subjects, correlating with the impaired bilirubin conjugate and bile acid secretion. The mRNA of MRP3, functioning as an inducible export pump for bilirubin conjugate and bile acid, was expressed not only in the cholestatic liver but also in the liver of control subjects, and the mRNA level was increased in specimens from both the cholestatic liver that had been well drained and from the liver that had been poorly drained. Immunostaining of MRP3 was observed in the epithelia of intrahepatic bile ducts in the liver of both control subjects and cholestatic patients, and in the epithelia of proliferated bile ductules and the hepatocytes surrounding the portal tracts in the cholestatic liver. CONCLUSIONS: From the results of the present study, it is concluded that 1) the mRNA and immunohistochemical expression levels of MRP2 and BSEP may be altered in the cholestatic liver of patients undergoing PTBD; 2) both the decreased mRNA levels and the diminished canalicular membrane localization may be associated with the impairment of bile formation and secretion, i.e., the efficacy of PTBD; and 3) upregulated MRP3 in the cholangiocytes and hepatocytes may play a significant role in bile acid transport in the cholestatic hepatobiliary system. PMID- 11774952 TI - How much reduction in portal pressure is necessary to prevent variceal rebleeding? A longitudinal study in 225 patients with transjugular intrahepatic portosystemic shunts. AB - OBJECTIVES: This longitudinal study determines the risk of rebleeding in relation to the reduction of the portosystemic pressure gradient in patients with a transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding. METHODS: The study included 225 patients in whom a TIPS revision was indicated by the endoscopic finding of varices with a high risk for rebleeding (n = 167) or a recent variceal rebleed (n = 58). The portosystemic pressure gradient was determined before and after TIPS placement and at revision performed after a mean of 10 +/- 15 months. RESULTS: The portosystemic pressure gradient at revision approached the index pressure gradient before TIPS implantation (23.1 +/- 5.5 mm Hg) by 8.4 +/- 31%. Rebleeding was inversely correlated with the reduction in index pressure gradient found at revision. Thus, 80% of rebleedings occurred with pressure gradients close to the index pressure gradient (< 25% reduction) or with gradients equal to or greater than the index pressure gradient. In contrast, only one patient (0.4%) and three patients (1.3%) rebled with a pressure gradient of < 12 mm Hg or a reduction of the index pressure gradient by > 50%, respectively. Kaplan-Meier analysis of rebleeding, which included the 225 patients at risk, showed a probability of rebleeding of 18%, 7%, and 1% for a reduction of the index pressure gradient by 0%, 25-50%, and > 50%, respectively. CONCLUSIONS: Most rebleedings occurred with pressure gradients similar to the index-pressure gradient measured at first bleeding. Accordingly, a graded reduction by 25-50% sufficiently prevents rebleeding. It can be assumed that, in comparison with the widely used threshold value of 12 mm Hg, a reduction by 25-50% may have a favorable benefit-to-risk ratio with respect to shunt-induced hepatic encephalopathy and liver failure. It should therefore be a goal in the decompressive treatment of portal hypertension and maintained during follow-up of patients with variceal bleeding. PMID- 11774953 TI - Tissue viral load variability in chronic hepatitis C. AB - OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology. PMID- 11774954 TI - Autoimmune hepatitis in African Americans: presenting features and response to therapy. AB - OBJECTIVES: African Americans are at an increased risk for certain diseases and more frequently suffer complications of those diseases relative to their white counterparts. Most studies of autoimmune hepatitis consist of entirely white populations. The Emory University system of hospitals serves a large African American population, including a significant number of African Americans with autoimmune hepatitis. The goal of this study was to determine if the presentation and response to therapy in African Americans is, like other diseases, different than in whites. METHODS: This is a retrospective study from a tertiary referral center that examines the initial presenting features and response to therapy of African Americans (n = 27) and whites (n = 24) with autoimmune hepatitis. RESULTS: Eighty-five percent of African Americans had cirrhosis on the initial liver biopsy, as compared with 38% of whites. Although not statistically significant, the African Americans presented at an earlier age than white patients. The disease also appeared more advanced in African Americans, as bilibubin levels tended to be higher, but not significantly, and PTs were more prolonged. Both groups responded well to therapy, with significant falls in serum levels of AST, ALT, and bilirubin. Fifty percent of African Americans and 48% of whites entered a biochemical remission. The amount of prednisone required to maintain remission at follow-up was greater in African Americans. CONCLUSION: In contrast to whites, the majority of African Americans present with cirrhosis. Despite the high prevalence of cirrhosis, the response to therapy is good. However, more immunosuppression is required to control the disease in African Americans. PMID- 11774955 TI - Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction. AB - OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by arterial hypoxemia in patients with chronic liver disease caused by abnormal intrapulmonary vasodilations. Data on its frequency vary from 5% to 29%. Most of these studies are from the West and in patients with cirrhosis. We, therefore, studied the prevalence of HPS in patients with liver cirrhosis and extrahepatic portal venous obstruction (EHPVO). METHODS: We studied 54 consecutive patients with liver cirrhosis (42 men and 12 women; mean age = 44.2 +/- 13 yr; Child grade A: 13, B: 22, and C: 19) and 50 patients with EHPVO (31 men and 19 women; mean age = 23.3 +/- 7.8 yr) Diagnosis of cirrhosis was made by history, liver function abnormalities, endoscopy, and sonography, whereas EHPVO was diagnosed by demonstration of a block in the splenoportovenous axis on sonography. Each of the patients underwent chest x-ray, arterial blood gas analysis, contrast-enhanced echocardiography (CEE), and pulmonary function tests. HPS was diagnosed in a patient with positive CEE, in the presence of hypoxia (PaO2 < 70 mm Hg) and/or elevated alveolar arterial oxygen gradient of > 20 mm Hg in the absence of any underlying cardiopulmonary disease. RESULTS: Ten of 54 patients (18.5%) with cirrhosis were positive on CEE compared with two of 50 patients (4%) with EHPVO. Six of the 10 patients positive with cirrhosis for CEE had associated hypoxia, whereas only one EHPVO patient with positive CEE had an elevated pulmonary alveolar arterial oxygen gradient of > 20 mm Hg. Thus, the incidence of HPS was 11.1% in patients with cirrhosis, compared with 2% in patients with EHPVO. One patient with HPS and cirrhosis had clinical cyanosis. CONCLUSION: HPS occurs more commonly in patients with cirrhosis but can also be seen in patients with EHPVO. PMID- 11774956 TI - Serum and colon mucosa micronutrient antioxidants: differences between adenomatous polyp patients and controls. AB - OBJECTIVES: Micronutrient antioxidants, by virtue of their free radical scavenging properties, are potential chemopreventive agents against colon cancer. Yet, little is known about the actual concentration of these antioxidants in colonic mucosa. It is also not known whether a relationship exists between serum and mucosal tissue antioxidant levels. Previous studies evaluating the occurrence of polyps after supplementation with vitamin E and beta-carotene have yielded mixed results. The aim of this study was to determine the concentrations of seven micronutrient antioxidants (alpha- and gamma-tocopherol, lutein, beta cryptoxanthin, lycopene, and alpha- and beta-carotene) in colonic mucosa and to determine whether serum levels of each antioxidant could predict levels of that antioxidant in the right and left colon of patients with normal mucosa or in those with adenomatous polyps. METHODS: Mucosal tissue concentrations and serum levels of antioxidants were determined in 10 patients with adenomatous polyps and 15 control subjects (GI patients with normal colonic mucosa). Mucosal tissue samples were obtained from both the right and left colon in all patients. RESULTS: Patients with polyps similar serum antioxidant status similar to that of control. However, polyp patients had significantly lower concentrations of all seven antioxidants in both the right (p < 0.0070) and left colon (p < 0.0026) than did controls. Finally, serum antioxidant levels predict right and left colon antioxidant levels in controls but not in patients with polyps. CONCLUSIONS: Patients with adenomatous polyps have low levels of micronutrient antioxidants in their colon mucosa. Because the serum levels of these antioxidants were similar in controls and polyp patients, our findings suggest an increased level of free radical activity in patients with polyps compared to normal subjects. PMID- 11774957 TI - Relationship between Helicobacter pylori CagA status and colorectal cancer. AB - OBJECTIVES: Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status. METHODS: In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses. RESULTS: H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA- was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7-41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3-1229.2; p = 0.001). CONCLUSIONS: Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer. PMID- 11774958 TI - Physician specialty and the outcomes and cost of admissions for end-stage liver disease. AB - OBJECTIVES: Chronic liver disease is a frequent cause of morbidity and mortality. The aim of this study was to characterize the effects of physician specialty on length of stay, mortality, and costs during hospitalizations for end-stage liver disease. METHODS: We used data from the HBS International EXPLORE database. Patients hospitalized for treatment of variceal hemorrhage, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified from primary discharge diagnoses. Patients were characterized by the specialty of the attending physician and by whether a gastroenterology consultation was obtained. Procedures performed were identified using ICD-9CM procedure codes. Costs were computed using proprietary HBS International Standard Transaction Codes. Linear and logistic regression analyses were used to examine the effect of physician specialty and consultation on length of stay, in-hospital mortality, and costs. RESULTS: Attending gastroenterologist care was associated with a shorter length of stay compared to nongastroenterologist attending care (median 4 vs 5 days, p = 0.01), which persisted after adjustment for differences in patient age, comorbidity, and number of procedures performed. There was a strong trend toward greater in-hospital mortality for patients without a gastroenterology attending or consultant (adjusted OR 1.72; 95% CI = 0.99, 2.98) compared to patients with a gastroenterology attending. Costs of hospital care were not significantly different between physician groups. CONCLUSIONS: Gastroenterologist involvement in inpatient care for end-stage liver disease was associated with shorter length of stay and a strong trend toward improved survival. Hospital costs were similar for patients cared for by the different physician groups. PMID- 11774959 TI - Genetic polymorphism of N-acetyltransferase 2 in patients with esophageal cancer. AB - OBJECTIVE: N-Acetylation polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there remains a controversy and no consensus concerning whether there is a true association between esophageal cancer and N-acetylation polymorphism. METHODS: To analyze the distribution of N-acetyltransferase 2 polymorphism in Japanese patients with esophageal squamous cell cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism was used. RESULTS: Based on an analysis of 71 Japanese patients with esophageal squamous cell cancer and 329 healthy control subjects, the distribution of the slow acetylator phenotype was significantly higher in esophageal cancer patients than in the controls (19.7% and 9.4%, respectively, p = 0.040). The odds ratio of esophageal cancer for the slow phenotype was 2.55 (95% CI = 1.15-5.65, p = 0.023) compared with the rapid type. Furthermore, a significant difference between the distribution of acetylator phenotype and the incidence of lymph node metastasis and lymphatic involvement was found based on the clinicopathological features of these cancers. Esophageal cancer patients with a higher smoking exposure history tended to have the rapid acetylator phenotype. CONCLUSION: These results suggest that N-acetylation polymorphism may be implicated as a genetic trait affecting an individual's susceptibility and biological behavior of esophageal squamous cell cancer. PMID- 11774960 TI - The tourniquet. PMID- 11774961 TI - Meckel's diverticulum causing intestinal obstruction. AB - Meckel's diverticulum is an uncommon cause of acute abdominal pain and small bowel obstruction in adults. We present a case of a 31-yr-old man with recurrent vomiting and abdominal pain in whom the diagnosis of Meckel's diverticulum was not suspected until CT of the abdomen revealed multiple fluid-filled, dilated loops of ileum with distal collapse after normal abdominal radiographs. We suggest that CT may be helpful when the diagnosis of Meckel's diverticulum is suspected. PMID- 11774962 TI - Acute interstitial nephritis due to omeprazole. AB - Omeprazole is a proton pump inhibitor that is used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Thus far, 17 cases of acute interstitial nephritis (AIN) secondary to omeprazole have been described. Another case of AIN is described in a 36-yr-old woman presenting with nausea, vomiting, weight loss, and a rising serum creatinine concentration. Omeprazole therapy had ceased 2 wk before admission. AIN was diagnosed by renal biopsy and corticosteroid therapy was initiated. After 4 wk of therapy the serum creatinine concentration had normalized. Among the reported cases in the literature, AIN was diagnosed after an average of 2.7 months of therapy with 20-40 mg of omeprazole daily. Recurrence was universal on rechallenge. Common symptoms included fatigue, fever, anorexia, and nausea. The classic triad of fever, rash, and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, pyuria, eosinophilia, and anemia. Management consisted of withdrawal of omeprazole and corticosteroid therapy in some patients. All but one patient recovered normal renal function. Corticosteroid therapy was well tolerated and may have been beneficial. PMID- 11774963 TI - Methotrexate therapy for refractory chronic active autoimmune hepatitis. PMID- 11774965 TI - EUS--predicting the future? PMID- 11774964 TI - Interferon: benefit beyond hepatitis therapy? PMID- 11774966 TI - Ursodiol for all? PMID- 11774967 TI - Re: Morrow et al.--The ringed esophagus. PMID- 11774968 TI - Ringed esophagus: unclear relationship to gastroesophageal reflux disease. PMID- 11774969 TI - Re: Garcia-Samaniego et al.--Hepatocellular carcinoma in patients with HCV-HIV coinfection. PMID- 11774970 TI - Orbital myositis associated with ulcerative colitis. PMID- 11774971 TI - Avoidance of steroids by the early use of infliximab and 6-mercaptopurine in an adolescent with active Crohn's colitis. PMID- 11774972 TI - Hypoxic hepatitis related to profound anemia: how low can you go? PMID- 11774973 TI - Liver-kidney microsomal antibody-positive autoimmune hepatitis in the United States. PMID- 11774974 TI - Single dilation of symptomatic Schatzki ring with a large dilator is safe and effective. PMID- 11774975 TI - GI events leading to death in association with celecoxib and rofecoxib. PMID- 11774976 TI - Acute pancreatitis associated with Salmonella enteritidis. PMID- 11774977 TI - Preliminary results of a two-center trial with colchicine for the treatment of chronic hepatitis B. PMID- 11774978 TI - Complications of urgent and emergency endoscopy in patients with GI bleeding as a function of time. PMID- 11774979 TI - Allixin, a phytoalexin from garlic, inhibits the growth of Helicobacter pylori in vitro. PMID- 11774980 TI - Re: Morrow et al.--Ringed esophagus and GERD. PMID- 11774981 TI - Effect of nicotine on inflammatory bowel disease. PMID- 11774982 TI - Re: Rex et al.--Medical-legal risks of incident cancers after clearing colonoscopy. PMID- 11774984 TI - Air contrastography technique for successful urgent ERCP in a high risk allergic patient. PMID- 11774983 TI - Amount of expression of the tumor-associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa. PMID- 11774985 TI - Gabapentin-associated hepatotoxicity. PMID- 11774986 TI - Malignant atrophic papulosis presenting as gastroparesis. PMID- 11774987 TI - Cryptosporidium parvum in intestinal mucosal biopsies from patients with inflammatory bowel disease. PMID- 11774988 TI - CMV infection in severe refractory ulcerative and Crohn's colitis. PMID- 11774989 TI - Risk associated with reprocessed reusable endoscopic instruments. PMID- 11774990 TI - Proton pump inhibitors and gastric acid secretion. PMID- 11774991 TI - Liver cirrhosis in erythropoietic protoporphyria: improvement of liver function with ursodeoxycholic acid. PMID- 11774992 TI - Re: Howden et al--Management of heartburn. PMID- 11774993 TI - Treatment of colon pseudo-obstruction in Guillain-Barre syndrome. PMID- 11774994 TI - Metastatic small cell carcinoma presenting as acute hepatic failure. PMID- 11774995 TI - Life-threatening hypomagnesemic hypocalcemia and hypokalemia in celiac disease. PMID- 11774996 TI - Toxic interaction of didanosine and acetaminophen leading to severe hepatitis and pancreatitis: a case report and review of the literature. PMID- 11774997 TI - Previously undiagnosed infiltrating lobular carcinoma of the breast presenting as a gastric outlet obstruction. PMID- 11774998 TI - Automatic generation of alignments for 3D QSAR analyses. AB - Many 3D QSAR methods require the alignment of the molecules in a dataset, which can require a fair amount of manual effort in deciding upon a rational basis for the superposition. This paper describes the use of FBSS, a program for field based similarity searching in chemical databases, for generating such alignments automatically. The CoMFA and CoMSIA experiments with several literature datasets show that the QSAR models resulting from the FBSS alignments are broadly comparable in predictive performance with the models resulting from manual alignments. PMID- 11774999 TI - Fast prediction of hydration free energies from molecular interaction fields. AB - A novel empirical model is presented that allows the fast computation of hydration free energies with high accuracy. The linear model is based upon the separation of the free energy of hydration into a cavity and an interaction term. The cavity contribution is modeled as a linear combination of molecular volume and surface terms. The interaction part is derived from the statistical three dimensional (3D) free energy density and is modeled approximately as a molecular interaction field using the program GRID. A compression scheme is employed to represent this 3D information on the molecular surface by means of a linear combination of surface functions. A set of 81 small organic molecules with known experimental hydration free energies is used to determine the coefficients of the linear model by least squares regression. The fit is statistically significant yielding a correlation coefficient of 0.99, a root mean square error of 0.27 kcal/mol for the 81 molecules belonging to the training set, and 0.63 kcal/mol for an independent test set of 10 molecules. PMID- 11775000 TI - A putative three-dimensional arrangement of the human serotonin transporter transmembrane helices: a tool to aid experimental studies. AB - The human serotonin transporter is the molecular target for selective serotonin reuptake inhibitor drugs which are being used for treatment of depression. A three-dimensional model of the membrane spanning parts of the transporter was constructed. The transporter was assumed to consist of 12 transmembrane alpha helices. The model was based on published experimental data of cocaine binding to mutant transporters, amino acid sequence analysis, and interactive molecular graphics. The model suggests that a high affinity cocaine binding site is situated in a region of the model where Asp98 acts like an anchor, while a putative low affinity site is situated in another region with Glu508 as the anchoring amino acid. A series of docking experiments with various reuptake inhibitors were conducted, using interactive molecular graphics techniques combined with energy calculations and analysis of the transporter-ligand complexes. Experiments involving molecular mapping of ligand binding areas may benefit from using the current model in experimental design. From the current model, several amino acids were proposed as prime candidates for mutagenesis and subsequent ligand binding studies. Also for evaluation of results from site directed mutagenesis experiments with SERT and similar transporters we assume the model will be helpful. PMID- 11775001 TI - Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature. AB - This paper describes molecular dynamics simulations of prion protein at 300 and 500 K. This was undertaken to gain insight into the factors involved in the stability of prion protein. Simulations were done using the Particle Mesh Ewald (PME) method using a homology model of the C-terminal fragment of human prion protein and the NMR structure of the human prion protein. The simulations at both 300 and 500 K were stable. Simulations were also undertaken with a mutant known to be associated with prion disease: Asp178Asn. The Asp178Asn simulation trajectory was observed to be much less stable than for the wild-type protein trajectory. Significant breakdown in secondary structure was observed for Asp178Asn at 500 K. PMID- 11775002 TI - Homology modeling of the estrogen receptor subtype beta (ER-beta) and calculation of ligand binding affinities. AB - Estrogen is a steroid hormone playing critical roles in physiological processes such as sexual differentiation and development, female and male reproductive processes, and bone health. Numerous natural and synthetic environmental compounds have been shown capable of estrogenic effects. This area has been the focus of significant fundamental and applied research due both to the potential detrimental effects of these compounds upon normal physiological processes and to the potential beneficial effects of tissue-selective estrogen agonists/antagonists for the prevention and treatment of numerous diseases. Genomic effects of the active form of estrogen, 17beta-estradiol, are mediated through at least two members of the steroid hormone receptor superfamily, estrogen receptor subtype alpha (ER-alpha) and estrogen receptor subtype beta (ER beta). At the time of this work, the X-ray crystal structure of the ER-alpha had been elucidated, however, coordinates of the ER-beta were not publicly available. Based upon the significant structural conservation across members of the steroid hormone receptor family, and the high sequence homology between ER-alpha and ER beta (>60%), we have developed a homology model of the ER-beta structure. Using the crystal structure of ER-alpha and the homology model of ER-beta, we demonstrate a strong correlation between computed values of the binding-energy and published values of the observed relative binding affinity (RBA) for a variety of compounds for both receptors, as well as the ability to identify receptor subtype selective compounds. Furthermore, using the recently available crystal structure of ER-beta for comparison purposes, we show that not only is the predicted homology model structurally accurate, but that it can be used to assess ligand binding affinities. PMID- 11775003 TI - Flexibility of the murine prion protein and its Asp178Asn mutant investigated by molecular dynamics simulations. AB - Inherited forms of transmissible spongiform encephalopathy, e.g. familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia, segregate with specific point mutations of the prion protein. It has been proposed that the pathologically relevant Asp178Asn (D178N) mutation might destabilize the structure of the prion protein because of the loss of the Arg164-Asp178 salt bridge. Molecular dynamics simulations of the structured C terminal domain of the murine prion protein and the D178N mutant were performed to investigate this hypothesis. The D178N mutant did not deviate from the NMR conformation more than the wild type on the nanosecond time scale of the simulations. In agreement with CD spectroscopy experiments, no major structural rearrangement could be observed for the D178N mutant, apart from the N-terminal elongation of helix 2. The region of structure around the disulfide bridge deviated the least from the NMR conformation and showed the smallest fluctuations in all simulations in agreement with hydrogen exchange data of the wild type prion protein. Large deviations and flexibility were observed in the segments which are ill-defined in the NMR conformation. Moreover, helix 1 showed an increased degree of mobility, especially at its N-terminal region. The dynamic behavior of the D178N mutant and its minor deviation from the folded conformation suggest that the salt bridge between Arg164 and Asp178 might not be crucial for the stability of the prion protein. PMID- 11775004 TI - Superimposition-based protocol as a tool for determining bioactive conformations. II. Application to the GABA(A) receptor. AB - The natural templates (NT) superimposition method is used to determine the pharmacophoric requirements of the A subtype of the gamma-aminobutyric acid (GABA) receptor. Bioactive conformations for antagonists and agonists are found by superimposing them on a relatively rigid alkaloid bicuculline, which itself is a competitive antagonist at this ligand-gated ion channel receptor. As has been usual in the application of this modeling method, consideration of available experimental data is the cornerstone for obtaining realistic models. The identification of two substructural fragments of bicuculline permitted classification of the ligands. Analysis of the antagonists and agonists with respect to the two substructural fragments revealed two bioactive conformations of the highly flexible GABA molecule, one of which is extended with the nonhydrogenic atoms roughly coplanar torsional angles of -37 and -179 degrees at N-C-C-C and C-C-C-C (carboxyl), respectively. The second bioactive compound is clearly non planar (torsional angles of -81 and -109 degrees at N-C-C-C and C-C-C C (carboxyl), respectively). PMID- 11775005 TI - Autologous endometrial coculture in patients with in vitro-fertilization (IVF) failure: correlations of outcome with leukemia inhibiting factor (LIF) production. AB - PROBLEM: To determine if LIF produced by autologous endometrial co-culture (ECC) was associated with outcome in 46 patients with a history of multiple IVF failures. METHOD OF STUDY: The conditioned media (CM) from ECC cells exposed or non-exposed to human embryos was analyzed for LIF. RESULTS: Exposure or non exposure to an embryo did not result in differing levels of LIF in the CM. LIF levels were significantly greater in the CM than in the serum controls (LIF was not found in the serum controls). Embryos grown on ECC demonstrated a significant improvement in number of blastomeres and fragmentation when compared to embryos grown in conventional media without ECC (6.7 +/- 1.3 vs. 5.6 +/- 1.2 blastomeres and 17.6% +/- 9.3 vs. 26.4% +/- 9.8 fragmentation; P < 0.05). When LIF levels were detectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media and demonstrated a non significant increase in pregnancy rates (60 vs. 48%, P = 0.50). CONCLUSIONS: We have demonstrated a significant improvement in embryo quality with ECC. The cells in the ECC express LIF. The presence of LIF in the CM was associated with embryonic development and clinical pregnancy. PMID- 11775006 TI - Immunoprotection of gonads and genital tracts in human embryos and fetuses: immunohistochemical study. AB - PROBLEM: The immune protection of genital organs in embryogenesis has not been sufficiently studied. The purpose of this study was to investigate the development of the secretory immune system (SIS) in the gonads and genital tracts of human embryos and fetuses. MATERIALS AND METHODS: Developing gonads at different stages and genital tracts from 18 embryos and 39 fetuses in the first to third trimester of gestation were analyzed for presence of different component of SIS: secretory component (SC), joining (J) chain. IgA, IgM, IgG, macrophages, and subsets of lymphocytes. The material was divided into two groups: cases not subjected to foreign antigenic effects (group I, n = 31) and those under antigenic attack (chorioamnionitis, group II, n = 26). RESULTS: In embryos and fetuses of group I, SC, J chain, and IgG were seen in the epithelium of mesonephric and paramesonephric ducts, proliferating coelomic epithelium, epithelium of the uterine tubes and uterus, epithelium of the vas deferens, epididymis, and rete testis. IgA and IgM appeared in 6-week-old embryos. J chain, IgA, IgM, and IgG, but not SC, were found in the primary oocytes and oogonia, spermatogonia. and interstitial cells. An abundance of macrophages was seen in 4 week-old embryos. T and B lymphocytes first appeared in 6-7-week-old embryos. In embryos and fetuses of group II, reactivity of immunoglobulins (Igs) decreased until they disappeared altogether. CONCLUSIONS: Components of SIS were seen in genital organs in 4-5-week-old embryos and were present during the whole intrauterine period. We suggest the presence of two forms of immune protection of fetal genital organs. One form contains SC, J chain, and Igs and is present in the genital tract epithelium. The second form contains only J chain and Igs and is present in germ cells of gonads. The loss of Igs in cases with chorioamnionitis reflects the functional participation of the SIS of genital organs in response to antigen attack. PMID- 11775007 TI - Increase in the production of interleukin-10 early after implantation is related to the success of pregnancy. AB - PROBLEM: To study the correlation of interleukin (IL)-10, IL-11 leukemia inhibitory factor (LIF), placental growth factor (PIGF), and transforming growth factor (TGF)-beta and outcome of human pregnancy. METHOD OF STUDY: We prospectively measured the serum levels of these cytokines in patients undergoing in vitro fertilization (IVF) programs. A total of 60 women (non-pregnant, n = 27; early abortions, n = 12; normal pregnancies, n = 21) were enrolled. RESULTS: There was no difference in the cytokines studied on D0 and D14 among the three groups of women. The increase in PIGF from D0 to D14 after human chorionic gonadotropin (hCG) injection was greater in pregnant women than in non-pregnant women; however, the difference did not reach significance (P = 0.068). The increase in IL-10 production from D14 to D21 was significant in women with successful pregnancies compared to women in the abortion group. CONCLUSIONS: This increase in IL-10 may be important in sustaining a normal pregnancy early after implantation. PMID- 11775008 TI - Synergistic effect of interleukin-1alpha and ceramide analogue on production of prostaglandin E2 and F2alpha by endometrial stromal cells. AB - PROBLEM: Prostaglandins (PGs) are synthesized in the endometrium. Our objective was to evaluate interleukin (IL)-1alpha-induced production of PGE2 and PGF2alpha in endometrial stromal cells (ESC) following treatment with ceramide analogues. METHODS OF STUDY: ESC were obtained from human uterine endometrium by enzymic digestion and filtration. ESC were treated with IL-1alpha, IL-1 receptor antagonist (ra), C2-ceramide and C6-ceramide. The concentrations of PGE2 and PGF2alpha in media were determined using ELISA. The induction of prostaglandin H synthase (PGHS)-2 mRNA was also ascertained by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The production of PGE2 and PGF2alpha was significantly increased by IL-lalpha and suppressed by IL-1 ra, in a dose dependent manner. PGF2alpha production was further increased by treatment with the combination of IL-1alpha and C2-ceramide as compared with IL-1alpha treatment alone. There was no significant difference in PGE2 production between cells treated with IL-1alpha and C2-ceramide and those treated with IL-1alpha alone. Both PGE2 and PGF2alpha production were significantly increased by treatment with IL-1alpha and C6-ceramide as compared with IL-1alpha treatment alone. Treatment of ESC with IL-1alpha stimulated PGHS-2 mRNA. PGHS-2 mRNA was decreased when IL-1 ra was added to the IL-1alpha-stimulated cells. CONCLUSIONS: These results suggest that IL-1alpha stimulates the production of PGE2 and PGF2alpha by a mechanism that involves the sphingomyelin-ceramide system, and thus that ceramide may be important in increasing the production of PGE2 and PGF2alpha in the human endometrium. PMID- 11775009 TI - Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulation of NK cell activity and subsets. AB - PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets. METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies. RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre-infusion NK cell activity (mean + SD. 40.9 + 17.0%) at 4.4 +/- 0.5 weeks of gestation (GW) decreased to 15.0 +/- 7.90% at post-infusion status (5.4 +/- 0.5 GW). Pre-infusion percentages of CD56+ CD16- cells (3.5 +/- 2.1%) and CD56+ CD16- cells (16.8 +/- 8.8%) decreased to 3.0 +/- 2.2% and 11.1 +/- 6.9%, respectively, after MIVIg treatment. CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment. PMID- 11775010 TI - The effects of pregnancy on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats: suppression of clinical disease, modulation of cytokine expression in the spinal cord inflammatory infiltrate and suppression of lymphocyte proliferation by pregnancy sera. AB - PROBLEM: The present study was performed to explore the effects of pregnancy on experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by inoculation with myelin basic protein (MBP) (MBP-EAE). METHOD OF STUDY: MBP-EAE was induced in pregnant and non-pregnant rats and severity of disease evaluated. Serum from pregnant and non-pregnant rats was used in standard lymphocyte proliferation assays. Real-time polymerase chain reaction (PCR) was used to investigate the expression of cytokine mRNA in the inflammatory cells obtained from the spinal cord of rats on day 15 after inoculation. RESULTS: Pregnant rats developed less severe disease than non-pregnant rats. Serum from pregnant rats suppressed the proliferation of T lymphocytes in response to MBP. There was significantly increased expression of IL-4, IL-10 and TNF-alpha mRNA in the spinal cord infiltrate of pregnant rats. CONCLUSION: Circulating humoral factors and alteration in cytokine production by inflammatory cells may contribute to the suppression of EAE in pregnant rats. PMID- 11775011 TI - Expression of interleukin-1beta mRNA in murine uterine and gestational tissues: relationship with gestational age. AB - PROBLEM: The pro-inflammatory cytokine interleukin (IL)-1beta has been shown to stimulate the production of prostaglandins (PG) in gestational tissues. Increased PG synthesis is considered a key step in the initiation of labor both at term and preterm. In this study. IL-1beta mRNA in the uterus and gestational tissues of mice during mid to late pregnancy was studied to characterize its tissue specific as well as gestational age expression. METHOD OF STUDY: Gestational tissues (placenta. decidual cap and fetal membranes). uterus, and cervix were collected from pregnant mice during gestation. Total RNA was isolated and probed for the expression of IL-1beta mRNA. RESULTS: There was a significantly increased expression of IL-1beta mRNA in the uterus on day 18 of pregnancy. In the decidual caps, there was increased expression of IL-1beta mRNA on day 14 of pregnancy and a decrease in expression with the onset of labor. In the fetal membranes and placenta, IL-1beta mRNA expression significantly increased on days 14 and 18 of pregnancy. respectively, and then remained elevated for the duration of pregnancy. In the cervix, there was a decrease in expression with labor onset. CONCLUSIONS: The increases in IL-1beta mRNA in the fetal membranes and placenta late in pregnancy are consistent with a localized, tissue specific inflammatory activation involved in the initiation of parturition. PMID- 11775012 TI - Protective vaccination against genital herpes simplex virus type 2 (HSV-2) infection in mice is associated with a rapid induction of local IFN-gamma dependent RANTES production following a vaginal viral challenge. AB - PROBLEM: To investigate the production of the CC chemokines RANTES. MCP-1, and MlP-1alpha in the vaginal mucosa following HSV-2 challenge in vaccinated and unvaccinated mice. METHOD OF STUDY: The concentrations of the chemokines were determined in the vagina of HSV-2-vaccinated as well as unvaccinated mice after HSV-2 challenge using a PERFEXT method combined with ELISA. RESULTS: HSV-2 infection did not induce any measurable levels of MIP-1alpha, whereas high levels of RANTES and MCP-1 were detected in unvaccinated animals at 48 hr post challenge. The vaccinated mice developed a more rapid induction of RANTES, but not of MCP-1, appearing as early as 24 hr post challenge. The local induction of RANTES production was preceded by a vaginal IFN-gamma response. Furthermore, vaccinated IFN-gamma-/- mice did not produce any enhanced levels of RANTES following HSV-2 challenge. CONCLUSIONS: The protective immune response against genital HSV-2 infection is associated with a rapid induction of local IFN-gamma dependent RANTES production. PMID- 11775013 TI - Neuronal changes in the arcuate and hypoglossal nuclei of brain stem induced by head injury. AB - In head injury, assessing the damage not only to the cerebrum and the cerebellum but also to the brain stem is very important. In this paper, we report neuronal changes of the arcuate nucleus (ARC) and the hypoglossal nucleus (HN) in the brain stem. We investigated these changes immunohistochemically with antibodies against microtubule-associated protein 2 (MAP2), muscarinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos), and the 72 kD heat-shock protein (HSP70). We measured the percentage of immunopositive neurons among the total neurons of the ARC and the HN. The investigation of neuronal changes in relation to the type of head injury showed different results. In cases of tonsillar herniation, immunoreactivity to MAP2 and mAChR in the ARC was significantly lower than in the HN (p < 0.01). Moreover, MAP2, HSP70 and c-Fos reactivities in the ARC were significantly lower than in other types of head injuries (p < 0.01). In the HN, diffuse axonal injury produced slightly higher immunoreactivity to mAChR and c-Fos (p < 0.1). Our observations indicate that immunohistochemical examination of brain stem nuclei can provide useful information for estimating damage to the brain stem. PMID- 11775014 TI - Analysis of disputed single-parent/child and sibling relationships using 16 STR loci. AB - This study describes the validation of short tandem repeat (STR) systems for the resolution of cases of disputed parentage where only a single parent is available for testing or where the claimed relationship of both parents is in doubt and also cases where sibship must be tested. Three separate multiplex systems the Second Generation Multiplex, Powerplex 1.2 and FFFL have been employed, giving a total of 16 STR loci. Both empirical and theoretical approaches to the validation have been adopted. Appropriate equations have been derived to calculate likelihood ratios for different relationships, incorporating a correction for subpopulation effects. An F(ST) point estimate of 1% has been applied throughout. Empirically, 101 cases of alleged father, alleged mother and child where analysed using six SLP systems and also using the three multiplex STR systems. Of the 202 relationships tested, 197 were independently resolved by both systems, providing either clear evidence of non-parentage or strong support for the relationship. PMID- 11775015 TI - Pitfalls in the analysis of mitochondrial DNA from ancient specimens and the consequences for forensic DNA analysis: the historical case of the putative heart of Louis XVII. AB - Amplification of mtDNA D-loop fragments with a length of 200 bp or more from ancient and even from fairly recent biological samples, can lead to erroneous results. This was clearly illustrated in our investigation of the putative heart of Louis XVII. By selecting different sets of primers which amplified shorter fragments of mtDNA (length 109 bp-201 bp), authentic polymorphisms could be visualised which remained undetected with the more classical primers for fragment sizes > 210 bp. Here we have extended those findings to other biological materials. A competitive PCR assay for quantitation of the amount of mtDNA for different fragment lengths, using a 10 bp deletion construct, was applied to ancient material and on a set of hairs of various ages of sampling (1966 up to the present). The results showed that DNA degradation started a few years after sampling. In the DNA extracts of the older hair shafts (1983-1995), the proportion of the number of short fragments to the number of long fragments is on average 4 in contrast to the most recent hair shafts. The numbers of amplifiable mtDNA copies for the hairs from 1975 and older were too small to show a clear difference. Use of long PCR fragments in such cases can yield misleading results. Use of short PCR fragments for the analysis of mtDNA from shed hair, in combination with a competitive PCR assay to determine the state of degradation, should improve the reliability of forensic mtDNA analysis considerably. PMID- 11775016 TI - Myocardial contraction bands. Definition, quantification and significance in forensic pathology. AB - Pathological contraction bands affecting myocardial cells are observed in many different human conditions and in different experimental models. Their morphology was defined long ago but we need to understand the pathogenesis and functional meaning. A distinction between different histological forms of contraction bands and their quantification in a large spectrum of human diseases (262 cases) and a normal population sample where death was due to various types of accidental death (170 cases) produced the following conclusions: 1) The term "contraction band necrosis", as used presently, is ambiguous and should be reserved for a specific morpho-functional entity induced experimentally by intravenous catecholamine infusion and seen in equivalent human cases with pheochromocytoma. 2) In human pathology it may represent a sign of adrenergic stress linked with malignant arrhythmia/ventricular fibrillation. 3) Beyond a histological threshold of 37+/-7 foci and 322+/-99 myocells/100 mm2, the lesion may indicate sympathetic overdrive in the natural history of a disease and associated arrhythmogenic supersensitivity. 4) The detection of few pathological contraction bands in normal subjects in some types of accidental death correlates with the survival time, suggesting an agonal adrenergic stimulation to promote the cardiac pump. PMID- 11775017 TI - A histological study on the mechanism of epidermal nuclear elongation in electrical and burn injuries. AB - Epidermal nuclear elongation is one of the most important signs for the diagnosis of electrical injury. In this study, we investigated the mechanism responsible for this phenomenon by comparing the findings from burn injuries and those from contusions. Electrical and burn injuries were made in the dorsal skin of rats using energy ranging from 100 to 790 joules for electrical injury, and 170-690 joules for burn injury. Contusions were also made by compressing the skin with a vice. In electrical and burn injuries, the dermis under the epidermal elongated nuclei was homogeneous and without empty spaces between collagen bundles and the number of dermal fibroblasts per 0.01 mm2 below the damaged epidermis decreased significantly (P < 0.05). The incidence of this change correlated with the depth of denatured dermal collagen fibres and in both types of injuries, dermal cells had no nuclear antigenicity for ubiquitin. The width of the injured epidermis with nuclear elongation decreased significantly (P < 0.05) and the elongated nuclei were parallel to the basal membrane. In electrical injury however, nuclear elongation occurred more frequently near the external root sheath. Nuclear elongation of fibroblasts and external root sheath cells was also found, but those of sebaceous gland cells were not detected. Epidermal elongated nuclei were also found in contusions. The evidence strongly suggests that epidermal nuclear elongation in electrical and burn injuries is due to dermal expansion by heat. PMID- 11775018 TI - Phosphatidylethanol in post-mortem blood as a marker of previous heavy drinking. AB - Phosphatidylethanol (PEth) is an ethanol-phospholipid adduct, formed via non oxidative metabolism of ethanol. PEth was measured in femoral blood from 85 consecutive forensic autopsies and was detected in 35 of the cases at concentrations ranging from 0.8 to 22.0 micromol/l. Of the PEth positive cases, 12 did not have significant levels of ethanol in the blood. Two cases (both suicides involving hanging) had detectable ethanol, but no PEth present in the blood. We conclude that measurements of PEth provide indications of previous alcohol abuse in cases where this may not otherwise be evident. PMID- 11775019 TI - Fatal blunt pancreatic trauma secondary to assault and battery: a case report. AB - The authors report on an fatal case of closed trauma of the pancreas in a context of violence. A 55-year-old man was found unconscious on the sidewalk and died a short time after being taken to the hospital. He had been hit with several punches to the face and abdomen 6 h before. The post-mortem examination showed numerous bruises over the whole body, a haemoperitoneum, a fissuration of the spleen and a massive peripancreatic haemorrhage associated with a complete dilaceration of the pancreas head. Histological examination of the pancreas revealed a massive necrosis associated with a subtotal disappearance of the acini, numerous sites of cytosteatonecrosis and a large haemorrhagic suffusion of the peripancreatic tissue. This case illustrates the possibilities of pancreatic injuries induced by blunt force aimed at the abdomen in a context of violence. Even if this occurs as an isolated injury it can result in rapid death because of the particular type of pancreatic fracture which is frequently involved. In postmortem situations, the pancreas should be systematically checked at necropsy and a histological examination should be carried out at the slightest doubt of a pancreatic lesion or suspicion of blunt force abdominal injuries. PMID- 11775020 TI - A dangerous design for a mountain bike. AB - The case of a man's death as a consequence of an accident with a mountain bike was examined. Despite only slight external injuries, a general examination revealed the existence of a rupture of the diaphragm which was the ultimate cause of death. The discussion reconstructs the way the accident occurred and briefly analyses the consequences of safety design in two-wheeled vehicles. PMID- 11775021 TI - Suicide by more than 90 stab wounds including perforation of the skull. AB - A man committed suicide in his bathroom using a small pocket knife. At the autopsy a total of 92 stab wounds on the forehead, in both temples, the anterior aspect of the neck, the back of the neck, the chest and the sides of the trunk were found. In addition, repeated stabbing had caused a large soft tissue defect on the forehead. The frontal bone showed 3 perforations but no brain injury was present and two ribs were severed in the bony part, one of which carried a star like pattern from repeated stabbing. No major vessels were injured and the cause of death was exsanguination after a considerable survival time. The large number of stab wounds, the perforation of bone and some injury sites, especially the head and back of the neck, are extraordinary findings in suicides which were probably favoured by insufficient anatomical knowledge and the use of a short bladed knife. A psychiatric history could not be verified. PMID- 11775022 TI - Symmetrical necrosis of the solitary tract nuclei as a contributory cause of death. AB - A 64-year-old man died in spite of surgery 4 days after attempting suicide. He first tried to hang himself with a rope and when the hanging did not succeed, he cut his throat with a knife. The autopsy showed four sutured cervical wounds with laryngeal wounds but without associated important vascular injury. The neuropathological study revealed two watershed-type haemorrhagic infarcts, involving the left occipital lobe and the left cerebellum. It also showed a symmetrical necrosis of solitary tract nuclei in the medullary tegmentum. Such a lesion is likely to result from sudden acute transient circulatory failure and might have played a role in the secondary autonomous cardiac and respiratory dysfunctions following a non-lethal trauma. PMID- 11775023 TI - Proof of a gunshot wound and its delayed effects 54 years post injury. AB - In 1945 a 6-year-old girl received a tangential gunshot injury to the left posterior inferior skull. After hospitalisation because of septicemia she was unable to walk for several months. Since 1967 she had been repeatedly applying for compensation because of pseudoneurasthenia and residual ataxia and many medical examinations were performed including X-ray, CT and MRI. Although certain objective findings (e. g. cerebellar atrophy) could be verified, a causal connection between the gunshot injury and the clinical findings could not be established. Therefore previous investigators concluded on a vascular origin of the disease. During the present re-examination of the patient, the authors found patch-like scars at the left posterior inferior skull base and behind the left ear, a cord-like scar formation in the subcutaneous tissue, connecting both skin scars, a gutter-like defect in the left occipital base of the skull and an indention of the left mastoid process, both again in line between the skin scars and a large defect of the left cerebellar hemisphere. It could be concluded with certainty that the anatomical findings and the clicinal symptoms were the direct result of a gunshot injury. Previous investigations had failed because of deficient investigations and techniques. In addition to an anatomical reconstruction, three dimensional reconstructions from CT scans proved most helpful. PMID- 11775024 TI - The STR locus D11S554: allele frequencies and sequence data in a Japanese population. AB - A population study on the short tandem repeat (STR) locus D11S554 was carried out in a sample of 362 unrelated Japanese individuals living in the Gifu Prefecture. A total of 46 different alleles ranging from 180 bp to 340 bp and 135 genotypes were revealed. Sequence analysis of alleles was carried out for 185 samples. The sequence structures of the repeat regions of the alleles were found to be complex and the alleles were classified into nine sequence types, including four new sequence types. According to the system of Adams et al. (1993), we designated the new sequence types IA3, IA4, IA5 and IB3, respectively. Out of the 46 different alleles, 11 showed sequence heterogeneity. The results of this study demonstrated that the D11S554 locus is a powerful and useful genetic marker for forensic practice in the Japanese population. PMID- 11775025 TI - Rac regulates vascular endothelial growth factor stimulated motility. AB - During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent. VEGF stimulated chemotaxis, is critically dependent on Rac activation. Osteopontin was a potent matrix activator of motility, and perhaps one explanation for the absence of a VEGF plus osteopontin effect is that osteopontin stimulated motility was inhibitory to the Rac pathway. PMID- 11775026 TI - The intracellular domain of cadherin-11 is not required for the induction of cell aggregation, adhesion or gap-junction formation. AB - The cadherin family of cell adhesion molecules demonstrates calcium-dependent homophilic binding, leading to cellular recognition and adhesion. The adhesion mediated by the classical type I cadherins is strengthened through catenin mediated coupling of the cytoplasmic domain to the cytoskeleton. This cytoskeletal interaction may not be essential for the adhesion promoted by all cadherins, several of which lack cytosolic catenin-binding sequences. Cadherin 11, a classical cadherin, possesses a cytoplasmic domain that interacts with catenins, but may also occur as a variant form expressing a truncated cytoplasmic domain. To study the role of the cytoplasmic sequence in cadherin-11 mediated adhesion we have constructed and expressed a truncated cadherin-11 protein lacking the cytoplasmic domain and unable to bind beta-catenin. Expression of the truncated cadherin-11 in MDA-MB-435S human mammary carcinoma cells reduced their motility and promoted calcium-dependent cell aggregation, frequent cell contacts, and functional gap-junctions. We conclude that the intracellular catenin-binding domain of cadherin-11, and by inference cytoskeletal interaction, is not required for the initiation and formation of cell adhesion. PMID- 11775028 TI - Bromodeoxyuridine induces integrin expression at transcriptional (alpha2 subunit) and post-transcriptional (beta1 subunit) levels, and alters the adhesive properties of two human lung tumour cell lines. AB - Integrins are a family of transmembrane glycoproteins that participate in a wide range of cellular events including proliferation, apoptosis and differentiation. Little is known about the mechanisms that control integrin subunit expression in epithelial cells, especially during lung cell differentiation. We have examined the effect of the differentiation-modulating agent, 5-bromo-2'-deoxyuridine (BrdU), on integrin expression in 2 human lung carcinoma cell lines, DLKP and A549. Treatment of both DLKP and A549 with 10 microM BrdU for 7 days resulted in increased expression of alpha2 and beta1 integrin subunit protein expression. Northern blot and RT-PCR analyses revealed progressively increasing levels of the alpha2 mRNA transcripts following BrdU treatment up to 21 days in both cell lines. However, no increase in beta1 integrin mRNA levels was observed in either cell, suggesting post-transcriptional regulation by BrdU. Treatment of HL-60, a leukaemic cell line, with BrdU up to 21 days resulted in no change in alpha2 or beta1 integrin subunit levels at either protein or mRNA levels suggesting that the change seen in the lung cell lines may be epithelial cell lineage-specific. BrdU has also been found to alter the adhesive properties of A549 and DLKP cells. Treated cells were found to adhere significantly faster to collagen type IV and laminin compared to untreated cells. The results presented here suggest that DLKP (and A549) may be useful cellular models to investigate the role of the alpha2beta1 integrin in lung epithelial cell differentiation. PMID- 11775027 TI - Characterization of morphological and cytoskeletal changes in MCF10A breast epithelial cells plated on laminin-5: comparison with breast cancer cell line MCF7. AB - The extracellular matrix regulates functional and morphological differentiation of mammary epithelial cells both in vivo and in culture. The MCF10A human breast epithelial cell line is ideal for studying these processes because it retains many characteristics of normal breast epithelium. We describe a distinct set of morphological changes occurring in MCF10A cells plated on laminin-5, a component of the breast gland basement membrane extracellular matrix. MCF10A cells adhere and spread on laminin-5 about five times more rapidly than on fibronectin or uncoated surfaces. Within 10 minutes from plating on laminin-5, they send out microfilament-rich filopodia and by 30 minutes acquire a cobblestone appearance with microfilaments distributed around the cell periphery. At 90 minutes, with or without serum, > 75% of the MCF10A cells plated on laminin-5 remain in this stationary cobblestone phenotype, while the remainder takes on a motile appearance. Even after 18 hours, when the culture is likely entering an exponential growth phase, the majority of cells maintain a stationary cobblestone appearance, though motile cells have proportionally increased. In contrast, the fully transformed, malignant human breast epithelial cells, MCF7, never acquire a stationary cobblestone appearance, do not organize peripheral microfilaments, and throughout the early time points up to 120 min appear to be constantly motile on laminin-5. We propose that changes in morphology and microfilament organization in response to laminin-5 may represent a benchmark for distinguishing normal vs. malignant behavior of epithelial cells derived from the mammary gland. This may lead to better model systems for studying the interactions between breast epithelium and the basement membrane extracellular matrix, which appear to be deregulated in processes like carcinogenesis and metastasis. PMID- 11775029 TI - European lecture: targets and approaches. 7th European Congress of Research in Rehabilitation, 2 April 2001, Madrid (edited version). PMID- 11775030 TI - Struck by stroke: a pilot study exploring quality of life and coping patterns in younger patients and spouses. AB - So far, research on quality of life after stroke has focused mainly on elderly patients. This study is targeted at younger stroke patients and their partners, aiming to evaluate stroke impact, as related to coping strategy. For our pilot study, eight patients who had suffered a stroke and four partners completed the Impact of Event Scale questionnaire. The mean age was 47.6 years in patients and 44.5 years in partners. The patients' level of activities of daily life was assessed using the Barthel Index. They were then interviewed to obtain information with respect to stroke impact and coping. The Schedule for the Evaluation of Individual Quality of Life procedure was carried out to measure quality of life, and stroke impact was quantified using Visual Analogue Scales. On average, patients scored 19.25 on the Barthel Index. Quality of life had deteriorated by 20.1% in patients, whereas partners did not show a decline in quality of life. However, well-being was inversely correlated among patients and partners. Accommodative coping was positively correlated with quality of life in both patients and partners. Conversely, assimilation was negatively related to quality of life in patients. PMID- 11775031 TI - Effectiveness of a multimedia programme and therapist-instructed training for children with autism. AB - The present study aimed to evaluate the effectiveness of an interactive multimedia training programme and a conventional therapist-instructed training in improving the learning behaviours of children with autism. A multiple-subject, single case-study time-series research design was adopted in the study. Six children with autism, aged 2 years 4 months to 2 years 10 months, were recruited by convenience sampling. They attended a 12-session training programme on basic concepts (e.g. colours, shapes) that was presented as an interactive multimedia training programme and also as a conventional, therapist-led training programme. The attending behaviours and appropriate responses of the subjects were videotaped for further analysis. Participants who attended the conventional therapist-instructed training programme generally showed improvement in attending behaviours and response rates; participants attending the multimedia programme also showed improvement in their attending behaviours and response rates. The results support the hypothesis that both training programmes are effective in improving the attending behaviours and appropriate responses of children with autism. The authors suggest that, because children with autism respond differently to different training approaches, customized training programmes should be considered for individual children. The implications of the methodology and the potential impact of the present study on the training of children with autism are discussed. PMID- 11775032 TI - Use of assistive devices to address hearing impairment by older persons with disabilities. AB - Hearing impairment impacts on the lives of almost half of people over the age of 65. For many people, a hearing aid or other assistive device can enhance communication. However, there is a high rate of dissatisfaction with hearing aids among those who currently use, or have used them in the past. This study of 227 elders with hearing impairment sought to gain a description of their multiple needs relative to demographics, health status physical status, and psychosocial status. Furthermore, we compared along the same dimensions the 227 elders with hearing impairment with 495 frail elders who reported no hearing impairment. We found that hearing-impaired elders are older, have poorer eyesight and have a high level of co-morbidity, especially with arthritis and heart and circulatory conditions. We also found a higher rate of depression among those with hearing impairment. Although hearing aid use increased as the impact of impairment on activity increased, three-quarters of those who reported that hearing impairment had a large impact on daily life did not use a hearing aid. A factor relating to hearing aid use was race; being Caucasian, and living alone. Study participants listed their reasons for dissatisfaction or non-use of their hearing aids and provided suggestions for hearing aid design. PMID- 11775033 TI - Effect of early vocational intervention in a rheumatological outpatient clinic--a randomized study. AB - This study aims to explore the effect of vocational intervention in a rheumatological outpatient clinic. The study is designed as a randomized study with intervention in 108 patients and with 93 patients serving as controls. The study population comprises patients referred for non-inflammatory diseases of the locomotor system who are all active members of the workforce and whose vocational status is threatened by their disease. Intervention consisted of sociomedical examination, multidisciplinary assessment and individual sociomedical rehabilitation plans. The study shows that intervention was an important instrument in the process of clarifying patients' future maintenance situation as assessed 1 year after intervention (relative risk (RR) = 1.2 (CI 1.0-1.5)). The effect was particularly prominent among well-educated women. A non-significant effect was established for vocational status in general (RR = 1.1 (CI 0.8-1.4)). This effect was significant and positive for well-educated patients with a short term sick leave (maximum 6 months). The verified effect of early sociomedical intervention in the secondary healthcare sector warrants the permanency of routine intervention. PMID- 11775034 TI - Enhancing an appointment diary on a pocket computer for use by people after brain injury. AB - People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury. PMID- 11775035 TI - Habilitation, support and service for young people with motor disabilities. A Swedish perspective. AB - 'Full participation in society' and 'equal opportunities' are key concepts in Scandinavian habilitation and rehabilitation policy. Few studies have been conducted concerning young people with disabilities and their life situation. This is a short report of a study based on a questionnaire answered by 477 young persons aged between 16 and 25 years, primarily with motor disabilities. The results show that they have fewer opportunities than young people in general to participate in social life. A conclusion is that improvements need to be made regarding the quality and quantity of habilitation support. PMID- 11775036 TI - Parental stress, marital satisfaction and responsiveness to children: a comparison between mothers of children with and without inborn impairment. PMID- 11775037 TI - Factors affecting participation in a child development programme. PMID- 11775038 TI - A comparative evaluation of two models of service delivery for families with a child with cerebral palsy. PMID- 11775039 TI - Backpropagation neural network short form of WAIS-R Japanese edition. PMID- 11775040 TI - Use of a contact lens telescopic system in low vision patients. AB - This study was designed to evaluate the effectiveness of a contact lens telescopic system in patients diagnosed with low vision. Fifteen white patients (mean age 60.7 years) with visual acuity between 20/60 and 20/400 (mean 20/245) were evaluated using first a conventional telescope and subsequently a contact lens telescope (CLT). Evaluation parameters were visual acuity, amplitude of visual field, and patients' satisfaction with the systems. The mean final visual acuity attained with both systems was 20/105. No differences in visual acuity between the two systems were detected. However, the visual field was significantly different with each system. Mean visual field with the conventional telescope was 22 degrees, whereas with the CLT it was 52.1 degrees. This corresponds to a reduction of 78.2% in the field of view with the conventional telescope and of 49.5% with the CLT. Therefore, the CLT was found to provide a field of view that is 136% as great as the one provided by the conventional telescope. Younger patients are specially enthusiastic about the CLT because of its improved cosmetic appearance and visual field as compared to traditional telescopes. Aged patients tend to have more difficulty in accepting and using contact lenses daily. PMID- 11775041 TI - Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 1, "Goldilocks" actions at dopamine receptors. AB - Dopamine system stabilizers are a potential new class of antipsychotic agents without motor side effects. All known effective antipsychotics act at D2 receptors. A novel concept for an antipsychotic without motor side effects is to stabilize these receptors rather than block them harshly. PMID- 11775042 TI - Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics. AB - BACKGROUND: Overweight is a considerable clinical problem in patients treated with antipsychotic agents. Recent results suggest that insulin resistance with increased insulin levels is also associated with treatment with the atypical antipsychotic agent clozapine. Leptin is important for the control of body weight and has been proposed to be a link between obesity and the insulin resistance syndrome. This study examined if clozapine-treated subjects and subjects treated with conventional antipsychotics had increased leptin levels compared with the general population and whether there was a gender difference in this respect. METHOD: Clozapine-treated patients (N = 41), patients treated with conventional antipsychotic drugs (N = 62), and healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project (N = 189) were investigated with a cross-sectional study design. Weight, body mass index (BMI), and plasma leptin concentrations were measured, and all study subjects were investigated for the presence of diabetes mellitus. Drug treatment, health status, and smoking habits were registered. RESULTS: After adjustment for gender, BMI, smoking habits, age, and diabetes, hyperleptinemia was independently (p < .001) associated with clozapine treatment and with treatment with conventional antipsychotics (p < .005) within a multiple regression analysis. In separate multiple regression analyses, leptin levels were significantly associated with clozapine treatment in men (p = .002) and women (p =.023) and with conventional antipsychotic treatment in men (p = .027) but not in women. CONCLUSION: Treatment with clozapine as well as with conventional antipsychotics is associated with increased levels of circulating leptin. Hyperleptinemia can be an important link in the development of overweight and the insulin resistance syndrome in subjects receiving antipsychotic drugs, especially atypical agents like clozapine. PMID- 11775043 TI - Olanzapine treatment of female borderline personality disorder patients: a double blind, placebo-controlled pilot study. AB - BACKGROUND: The intent of this study was to compare the efficacy and safety of olanzapine versus placebo in the treatment of women meeting criteria for borderline personality disorder (BPD). METHOD: We conducted a double-blind, placebo-controlled study of olanzapine in 28 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for BPD. The subjects were randomly assigned to olanzapine or placebo in a 2:1 manner. Treatment duration was 6 months. Primary outcome measures were self-reported changes on anxiety, depression, paranoia, anger/hostility, and interpersonal sensitivity scales of the Symptom Checklist-90. RESULTS: Nineteen subjects were randomly assigned to olanzapine; 9. to placebo. When random effects regression modeling of panel data was used, controlling for baseline level of severity, olanzapine was associated with a significantly (p < .05) greater rate of improvement over time than placebo in all of the symptom areas studied except depression. Weight gain was modest in the olanzapine-treated group but was significantly higher than in those treated with placebo (p < .02). In addition, no serious movement disorders were noted. CONCLUSION: Olanzapine appears to be a safe and effective agent in the treatment of women with criteria-defined BPD, significantly affecting all 4 core areas of borderline psychopathology (i.e., affect, cognition, impulsivity, and interpersonal relationships). PMID- 11775044 TI - Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt? AB - INTRODUCTION: Long-acting depot injections of antipsychotic medications are an important way to monitor treatment noncompliance in patients suffering from schizophrenia. Pain and discomfort at the injection site may result in patients' refusal of depot injections. The present study is a pilot study that attempts a systematic characterization of injection site pain. METHOD: Thirty-four consecutive outpatients suffering from DSM-IV-defined schizophrenia or schizoaffective disorder and treated with depot antipsychotic medications were evaluated. The pain they suffered from the injections was quantified using a visual analog scale. This evaluation was made 5 minutes before the injection, 5 minutes after. 2 days after, 10 days after, and before the next injection. Patients were also administered a modified version of the Rating of Medication Influences scale that included a specific question on the possible relationship between injection-associated pain and future compliance to depot treatment. RESULTS: The depot injections cause pain, which is maximal immediately after the injection, declines substantially 2 days after, and disappears by the tenth day after the injection. A correlation exists between reported injection site pain and the effect it has on patients' attitude toward the depot injection as reported by the patients. Zuclopenthixol depot injection is more painful than other depot medications. CONCLUSION: Depot injections are painful. The pain they inflict has a typical course, and medication type is among the factors that influence this pain. This pain might have an effect on patients' attitude toward depot injections and thus is of importance in the management of patients suffering from schizophrenia. PMID- 11775045 TI - Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. AB - BACKGROUND: The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined. RESULTS: 307 patients constituted the intent-to treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment. PMID- 11775046 TI - Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. AB - BACKGROUND: Most examinations of the clinical efficacy of drugs used to treat depression pool subjects across gender and age groups. This investigation compared these patient subpopulations on the basis of remission and response rates associated with venlafaxine and selective serotonin reuptake inhibitor (SSRI) treatment. METHOD: A meta-analysis of original data from 8 comparable double-blind, active-controlled, randomized clinical trials (4 also placebo controlled) was conducted. Antidepressant efficacy was assessed for patients (N = 2,045) aged 18 to 83 years (subgroups: < or = 40, 41-54, 55-64, and > or = 65 years) who met DSM-III-R criteria for major depression or DSM-IV criteria for major depressive disorder and were randomly assigned to receive venlafaxine (immediate release, N = 474; extended release, N = 377), one of several SSRIs (N = 748), or placebo (N = 446) for up to 8 weeks. Symptoms of depression were assessed using the Hamilton Rating Scale for Depression (HAM-D). Remission was defined as a HAM-D-17 score < or = 7, response was defined as > or = 50% decrease in HAM-D-21 score, and absence of depressed mood was defined as a HAM-D depressed mood item score of 0. RESULTS: We detected no significant age-by-treatment, gender-by-treatment, or age-by-gender-by-treatment interactions; men and women of different ages within a given antidepressant treatment group exhibited similar rates of remission, response, and absence of depressed mood. Regardless of age or gender, remission rates during venlafaxine therapy were significantly higher than during SSRI therapy (remission rates at week 8: venlafaxine, 40%-55% vs. SSRI, 31%-37%; p < .05). Regardless of patient age or gender, onset of remission was more rapid with venlafaxine than with SSRI treatment. By contrast, rates of absence of depressed mood with venlafaxine (34%-42%) and SSRIs (31%-37%) did not differ significantly and tended to be similar for all patient subgroups. CONCLUSION: These data suggest that men and women have comparable responses to SSRIs and venlafaxine across various age groups. Moreover, patients exhibited a more rapid onset and a greater likelihood of remission with venlafaxine therapy than with SSRI therapy regardless of age or gender. PMID- 11775047 TI - A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. AB - BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia. METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12. RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05). CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects. PMID- 11775048 TI - Comorbidity of axis I disorders in patients with traumatic grief. AB - BACKGROUND: Traumatic grief has been found to be a distinct disorder from both depression and anxiety; however, there is no information in the literature regarding comorbidity of traumatic grief with other psychiatric disorders. METHOD: Twenty-three bereaved subjects who presented for treatment of traumatic grief symptomatology were included in this study. The Inventory of Complicated Grief (ICG) was used to confirm the presence of traumatic grief and assess its severity. In addition, the Structured Clinical Interview for DSM-IV was performed. RESULTS: Most subjects met criteria for a current or lifetime Axis I diagnosis. Fifty-two percent (N = 12) met criteria for current major depressive disorder, and 30% (N = 7), for current posttraumatic stress disorder (PTSD). ICG scores and functional impairment were higher among patients with more than one concurrent Axis I diagnosis. CONCLUSION: Comorbid major depressive disorder and PTSD may be prevalent in patients presenting for treatment of traumatic grief. PMID- 11775049 TI - Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. AB - BACKGROUND: The efficacy of anxiolytic drugs in generalized anxiety disorder (GAD) is conventionally assessed by evaluating changes in the total score of psychometric scales such as the Hamilton Rating Scale for Anxiety (HAM-A). The purpose of this pooled analysis of data was to evaluate the efficacy of venlafaxine extended release (XR) on individual items of the HAM-A and the Brief Scale for Anxiety (BSA). METHOD: Data were pooled from 5 studies of patients with GAD who were treated with either venlafaxine XR or placebo for 8 weeks (N = 2,021) and up to 6 months (N = 767). Individual items of the HAM-A and the BSA were examined. and, using the mean changes from baseline to endpoint, an effect size for each item was calculated by dividing the difference between baseline and endpoint values for each item by the standard deviation of this difference. The effect sizes determined for the venlafaxine group were compared with those for the placebo group. Items from each scale that are concordant with the DSM-IV diagnostic criteria for GAD were selected for further examination, and the specific effect sizes of each item were expressed after controlling for placebo effects. RESULTS: The effect size of the majority of the 14 items of the HAM-A scale and the 10 items of the BSA scale associated with treatment with venlafaxine XR was greater than with placebo at both 8 weeks and 6 months. Furthermore, the effect sizes at 6 months were generally greater than at 8 weeks in venlafaxine XR-treated patients. Effect sizes associated with venlafaxine XR were greatest for the HAM-A items that were most closely related to diagnostic symptoms of GAD, namely anxious mood, tension, intellectual functioning, and behavior at interview at both 8 weeks and 6 months. Similarly, GAD-related BSA items of inner tension, worrying over trifles, hostile feelings, and muscular tension were associated with the greatest improvements with venlafaxine XR at both time-points. CONCLUSION: The HAM-A and BSA items that most closely corresponded to DSM-IV diagnostic criteria for GAD showed the largest improvement during treatment with venlafaxine XR. This indicates that the specific symptoms of GAD can be treated effectively with venlafaxine XR, both in the short and longer term. PMID- 11775050 TI - Effect of risperidone on behavioral and psychological symptoms and cognitive function in dementia. AB - AIMS: This open-label study examined the efficacy and tolerability of risperidone in the treatment of aggression, agitation, and psychotic symptoms in dementia. The influence of risperidone on cognitive function was also assessed under conditions reflecting normal, daily clinical care. METHOD: A total of 34 hospital inpatients and outpatients (mean age = 76 years) with DSM-IV dementia disorders were treated with flexible doses of risperidone (0.5-2 mg/day) for 8 weeks. Assessments, conducted at baseline and after weeks 4 and 8, included the Clinical Global Impressions scale (CGI) and Neuropsychiatric Inventory (NPI) ratings. Cognitive function assessments included the Mini-Mental State Examination (MMSE) and specific measures of cognition (Age Concentration Test [AKT] and Brief Syndrome Test [SKT]). Frequency of extrapyramidal symptoms (EPS) was measured according to the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: At the end of the study, 50% of patients (N = 17) were receiving risperidone, 1 mg/day. 18% (N = 6) were receiving 0.5 mg/day, and 32% (N = 11) received > 1 mg/day (mean dose at endpoint = 1.1 mg/day). An improvement in symptoms, as measured by the CGI-Global Impression of Change scale, was reported for 82% of patients (N = 28) (59% [N = 20] much or very much improved). The frequency and severity of delusions, hallucinations, agitation/aggression, and irritability decreased as measured by the NPI. Multiplication of frequency and severity scores revealed a significant decline during the course of treatment (p < .001, end of study vs. baseline). Caregiver responses on the NPI also showed an improvement, with the mean +/- SD total score decreasing from 24.2 +/- 7.3 at baseline to 21.2 +/- 6.3 at study end (p = .002). MMSE, AKT, and SKT results indicated that there was no decrease in cognitive function during the study. Risperidone treatment was well tolerated, and no clinically relevant changes in EPS. vital signs, or weight were detected. CONCLUSION: During treatment with low-dose risperidone, behavioral and psychological symptoms improved overall in 34 patients with dementia, and cognitive function was maintained throughout the treatment period. PMID- 11775051 TI - Antiaggressive effect of quetiapine in a patient with schizoaffective disorder. PMID- 11775052 TI - Body weight gain, insulin, and leptin in olanzapine-treated patients. PMID- 11775053 TI - Trauma and stress: diagnosis and treatment. Teleconference. August 6, 2001. PMID- 11775054 TI - Development of pigment cells in the brain of ascidian tadpole larvae: insights into the origins of vertebrate pigment cells. AB - In vertebrates, melanins produced in specialized pigment cells are required for visual acuity, camouflage, sexual display and protection from ultra violet (UV) radiation. There are three pigment cell types that are classified based on their distinct embryonic origins. Retinal pigment epithelium (RPE) cells originate from the outer layer of the optic cup. Pigment cells of the pineal organ are formed from the developing diencephalon. Melanocytes are derived from the neural crest unique to vertebrate embryos. Some of these pigment cells also play roles that are independent of the activity of tyrosinase, the key melanogenesis enzyme, or melanin: production of substrate(s) for catecholamine synthesis, maintenance of endolymph composition in the cochlea, maintenance of photoreceptor cells in the retina and retinoid metabolism essential for the visual cycle. To deduce the evolutionary origins of vertebrate pigment cells and a possible archetypal genetic circuitry, which may have been modified and utilized to generate multiple pigment cell types, comparison of developmental mechanisms of pigment cells between vertebrates and closely related invertebrate ascidians are proposed to provide useful information. The tadpole-type larva of ascidians possesses two melanin-containing pigment cells, termed the otolith and ocellus pigment cells, in the brain that are believed to be required for photo- and geotactic responses during swimming. In this review, current knowledge on the development of the two ascidian pigment cells is summarized, i.e. complete cell lineage, structure and expression of genes encoding two melanogenesis enzymes, and molecular developmental mechanisms involving BMP-CHORDIN antagonism, and possible evolutionary relationships between ascidian and vertebrate pigment cells are discussed. PMID- 11775055 TI - Tyrp1 and oculocutaneous albinism type 3. AB - Tyrosinase-related protein 1 (Tyrp1) is a melanocyte-specific gene product involved in eumelanin synthesis. Mutations in the mouse Tyrp1 gene are associated with brown pelage, and in the human TYRP1 gene with oculocutaneous albinism type 3 (OCA3). In the murine system, Tyrp1 expresses significant dihydroxyindole carboxylic acid oxidase (i.e. DHICA oxidase) activity. However, in humans, TYRP1 is enigmatic in that despite extensive efforts focused on the study of its function, its actual role in the human melanocyte is still unclear. There is mounting evidence demonstrating that in addition to its role in eumelanin synthesis, Tyrp1 is involved in maintaining stability of tyrosinase protein and modulating its catalytic activity. Tyrp1 is also involved in maintenance of melanosome ultrastructure and affects melanocyte proliferation and melanocyte cell death. The current review is an attempt to consolidate our understanding of the role of Tyrp1 in the melanocyte. PMID- 11775056 TI - Volume changes of individual melanosomes measured by scanning force microscopy. AB - Black pigment cells, melanophores, e.g. located in the epidermis and dermis of frogs, are large flat cells having intracellular black pigment granules, called melanosomes. Due to a large size, high optical contrast, and quick response to drugs, melanophores are attractive as biosensors as well as for model studies of intracellular processes; e.g. organelle transport and G-protein coupled receptors. The geometry of melanosomes from African clawed toad, Xenopus laevis, has been measured using scanning force microscopy (SFM). Three-dimensional images from SFM were used to measure height, width, and length of the melanosomes (100 from aggregated cells and 100 from dispersed cells). The volumes of melanosomes isolated from aggregated and dispersed melanophores were significantly different (P < 0.05, n=200). The average ellipsoidal volume was 0.14+/-0.01 (aggregated) and 0.17+/-0.01 microm3 (dispersed), a difference of 18%. The average major diameter was 810+/-20 and 880+/-20 nm for aggregated and dispersed melanosomes, respectively. To our knowledge, this is the first time SFM has been used to study melanosomes. This may provide an alternative non-destructive technique that may be particularly suitable for studying morphological aspects of various melanin granules. PMID- 11775057 TI - L-NAME-induced dispersion of melanosomes in melanophores activates PKC, MEK and ERK1. AB - Melanosome movement represents a good model of cytoskeleton-mediated transport of organelles in eukaryotic cells. We recently observed that inhibiting nitric oxide synthase (NOS) with Nomega-nitro-L-arginine methyl ester (L-NAME) induced dispersion in melanophores pre-aggregated with melatonin. Activation of cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) or calcium dependent protein kinase (PKC) is known to cause dispersion. Also, PKC and NO have been shown to regulate the mitogen/extracellular signal-regulated kinase (MEK)-ERK pathway. Accordingly, our objective was to further characterize the signaling pathway of L-NAME-induced dispersion. We found that the dispersion was decreased by staurosporine and PD98059, which respectively inhibit PKC and MEK, but not by the PKA inhibitor H89. Furthermore, Western blotting revealed that ERK1 kinase was phosphorylated in L-NAME-dispersed melanophores. L-NAME also caused dispersion in latrunculin-B-treated cells, suggesting that this effect is not due to inhibition of the melatonin signaling pathway. Summarizing, we observed that PKC and MEK inhibitors decreased the L-NAME-induced dispersion, which caused phosphorylation of ERK1. Our results also suggest that NO is a negative regulator of phosphorylations that leads to organelle transport. PMID- 11775058 TI - RelA, p50 and inhibitor of kappa B alpha are elevated in human metastatic melanoma cells and respond aberrantly to ultraviolet light B. AB - Metastatic melanomas are typically resistant to radiation and chemotherapy. The underlying basis for this phenomenon may result in part from defects in apoptotic pathways. Nuclear factor kappa B (NFkappaB) has been shown to control apoptosis in many cell types and normally functions as an immediate stress response mechanism that is rigorously controlled by multiple inhibitory complexes. We have previously shown that NFkappaB binding is elevated in metastatic melanoma cells relative to normal melanocytes. In the current study, Western blot analysis showed that, compared with normal melanocytes, melanoma cell lines have higher nuclear levels of the NFkappaB subunits p50 (7-fold) and RelA (5-10-fold). In response to tumor necrosis factor-alpha (TNFalpha), both melanocytes and melanoma cells showed increased nuclear p50 and RelA levels, but levels in melanoma cells remained higher than in melanocytes. We also found that melanoma cells expressed higher cytoplasmic levels of RelA, p105/p50 and the inhibitory protein, inhibitor of kappa B alpha (IkappaBalpha) than melanocytes. To directly test whether RelA expression has an impact on melanoma cell survival, we used antisense RelA phosphorothioate oligonucleotides and found that melanoma cell viability was significantly decreased compared with untreated or control cultures. The constitutive activation of NFkappaB in metastatic melanoma cell cultures may, therefore, support an inappropriate cell survival pathway that can be therapeutically manipulated. PMID- 11775059 TI - Development of cutaneous amelanotic melanoma in the absence of a functional tyrosinase. AB - Lack of characteristic pigmentation and a wide range of clinical presentations account for the diagnostic challenge associated with amelanotic malignant melanoma. Experimental studies of this important human cancer have been hampered by the lack of an appropriate animal model. We previously described a transgenic mouse line (TG-3) that spontaneously develops pigmented cutaneous melanoma. F1 crosses were generated with TG-3 and several albino strains, and backcrosses were then made with the albinos. In the present report, we describe the restricted development and characterization of cutaneous amelanotic melanoma in these albino transgenic backcrosses. The incidence and behavior of melanoma in these mice were monitored. A high incidence (80-100%) of spontaneous amelanotic melanoma was observed in albino transgenic mice derived from backcrosses with A, AKR, FVB, and SJL strains. The lowest incidence (30%) was obtained in BALB/c-derived crosses. No tumors were observed in non-transgenic mice. Immunohistochemical and western blot analyses using antibodies against three melanocyte-specific markers of the tyrosinase family of proteins confirmed that the tumors were composed of amelanotic melanocytes. Furthermore, the presence of numerous premelanosomes observed by electron microscopy further supported the melanocytic origin of these tumors. Previous in vitro studies on human melanoma have suggested that cutaneous amelanotic melanoma was evolving from preexisting pigmented cutaneous melanoma. However, our results indicate that it can occur directly, as evidenced by the appearance of cutaneous amelanotic melanoma in the tyrosinase-deficient albino mice. These mice represent a potentially valuable model for studying the mechanistic, diagnostic, and therapeutic features of this highly malignant neoplasm. PMID- 11775060 TI - 'VIT1', a novel gene associated with vitiligo. AB - To define genes associated with the pigmentary disorder vitiligo, gene expression was compared in non-lesional melanocytes cultured from three vitiligo patients and from three control melanocyte cultures by differential display. A basic local alignment search tool search did not reveal homology of six differentially expressed cDNA fragments to previously identified expressed sequence tags; thus, one was used to screen a melanocyte cDNA library. The underlying VIT1 gene maps to chromosome 2p16. The 3' portion of the VIT1 message is complementary to the 3' end of hMSH6 mRNA, enabling the formation of RNA-RNA hybrids, which may interfere with G/T mismatch repair function. Moreover, the aligned cDNA sequence revealed an open reading frame identical to a hypothetical protein expressed in brain, with a similarity to Drosophila calmodulin, and containing a zinc-finger motif partially identical to N-recognin. Expression of ORF mRNA was confirmed for multiple skin cell types, suggesting its importance for skin physiology. PMID- 11775062 TI - Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins. AB - 1. Increased production of A beta in a form of lipoprotein antioxidant under the action of increased oxidative stress in aging with subsequent chelation of transition metal ions by A beta, accumulation of toxic A beta-metal lipoprotein complexes, production of reactive oxygen species, and neurotoxicity are reviewed and postulated to form the temporal sequence of events in the development of Alzheimer's disease (AD). 2. Since (i) A beta binds copper stronger than iron and other transition metals, and (ii) copper is a more efficient catalyst of oxidation than other transition metals, chelation of copper by A beta is proposed to be a most important part of this pathway. 3. Whereas this amyloid-binds-copper (ABC) model does not remove A beta peptide from its central place in our current thinking of AD, it places additional factors in the center of discussion. 4. Most importantly, they embrace pathological mechanisms known to develop in aging (which is the most important risk factor for AD), such as increased production of reactive oxygen species by mitochondria, that can be positioned upstream relative to the generation of A beta. PMID- 11775061 TI - The ocular albinism type 1 gene product is an N-glycoprotein but glycosylation is not required for its subcellular distribution. AB - The ocular albinism type 1 (OA1) gene product is a membrane glycoprotein that may play a role in controlling melanosome growth and maturation. A number of mutations in the OA1 gene lead to ocular albinism due at least in part to retention of the aberrant protein in the endoplasmic reticulum. To examine whether N-glycosylation plays a role in the post-translational trafficking of the Oa1 protein, we constructed a series of mutant mouse Oa1 cDNAs encoding an Oa1 green fluorescent protein fusion in which some or all of the potential glycosylation sites were eliminated by site-directed mutagenesis. Biochemical studies in transfected cells treated with tunicamycin and peptide:N-glycosidase F suggest that asparagine at amino acid 106 is essential for N-glycosylation of the protein. Mutation at amino acid 106 that eliminated glycosylation did not affect the endo/lysosomal distribution of the Oa1 protein in either COS cells or cultured murine melanocytes. PMID- 11775063 TI - Cell density-dependent death mode switch of cultured cortical neurons under serum free starvation stress. AB - 1. Cell death mode switch of cortical neurons from E17 rats was studied. Cells rapidly died under the serum-free condition. The time-course of cell death was markedly delayed by increasing cell density for primary culture in the trypan blue exclusion, LDH release, and MTT assays. 2. By analyzing cell death by the use of double staining using PI/TUNEL and PI/Annexin V combinations, the mode in the low density culture was found to be necrosis, while that in the high density culture was apoptosis. 3. The intracellular ATP level after the start of serum free culture rapidly decline to 25% of 0-time level in the low density culture, but it was 60% in the high density culture. Both oligomycin and zVAD-fmk markedly decreased ATP levels and the population of TUNEL-positive neurons, while 3 aminobenzamide slightly increased these indices. 4. Thus. it is strongly suggested that the cell death mode switch from necrosis to apoptosis is closely related to intracellular ATP levels, and some conditioned medium factors observed in the high density culture may affect both ATP level and cell death mode switch. PMID- 11775064 TI - Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain. AB - 1. Phenelzine (PLZ) is an antidepressant with anxiolytic properties. Acute and chronic PLZ administration increase brain GABA levels, an effect due, at least in part, to an inhibition of the activity of the GABA metabolizing enzyme, GABA transaminase (GABA-T). 2. Previous preliminary reports have indicated that acute PLZ treatment also elevates brain alanine levels. As with GABA, the metabolism of alanine involves a pyridoxal phosphate-dependent transaminase. 3. In the study reported here, the effects of acute PLZ treatment on the levels of various amino acids, some of which are also metabolized by pyridoxal phosphate-dependent transaminases were compared in rat whole brain. Of the 6 amino acids investigated, only GABA and alanine levels were elevated (in a time- and dose dependent manner). 4. The elevation in brain alanine levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on alanine transaminase (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced. In addition, we also showed that the elevation in alanine levels and the inhibition of alanine transaminase in the brain are retained after 14 days of PLZ treatment, and that PLZ produces a marked increase in extracellular levels of alanine. 5. These results are discussed in terms of their relevance to synaptic function and to the pharmacological profile of PLZ. PMID- 11775065 TI - The lateral hypothalamus is involved in the pathway mediating the hypotensive response to cingulate cortex-cholinergic stimulation. AB - 1. The injection of acetylcholine (ACh) into the medial prefrontal cortex (MPFC) caused marked hypotensive response in either unanesthetized or anesthetized rats. 2. The present experiment was designed to investigate anatomical connections of the ACh injection site in the MPFC with putative autonomic-related brain nuclei, as well as their possible involvement in the mediation of the hypotensive response to ACh. 3. For the above purpose, the bidirectional neuronal tracer biotinylated dextran amine (BDA) was injected into Cg1 and Cg3 areas, within the MPFC of male Wistar rats. Five days later the animals were sacrificed and brain slices were processed and analyzed to determine neuronal projections efferent from as well afferent to the MPFC. 4. Neuronal staining was more prominent in regions ipsilateral to the BDA injection site. Prominent efferent projections of the MPFC were observed in the contralateral MPFC: ipsi- and contralateral amygdala and hypothalamus; ipsilateral septal area, diagonal band, and zona incerta. 5. Similar but not equal patterns of neuronal labeling were observed when BDA injections were performed within the two adjacent MPFC areas. BDA injections centered in the ACh injection site in the Cg3 area caused strong labeling in the septal area and diagonal band as well as an overall hypothalamic labeling. Within the hypothalamus an intense cortical projection was observed in the lateral hypothalamus (LH). BDA injections into the Cg1 area caused a more evident labeling of the amygdaloid complex. 6. Neuronal cell bodies were evident throughout the MPFC as well as in the sensory-motor cortex when BDA was injected into the LH, thus indicating a massive ipsilateral cortical projection from the Cg3 to the LH. 7. Bilateral NMDA-induced lesions within the LH caused a significant attenuation of the depressor responses to ACh injection in the MPFC, whereas unilateral lesions were marginally effective. These results indicate the involvement of the LH in the mediation of the hypotensive response to ACh injection into the MPFC as well as the bilateral distribution of the hypotensive pathway. PMID- 11775066 TI - Development of synaptic responses and plasticity at the SC-CA1 and MF-CA3 synapses in rat hippocampus. AB - 1. The development of synaptic transmission and indicators of short- and long term plasticity was studied by recording from areas CA1 and CA3 upon activation of monosynaptic excitatory inputs in rat hippocampal brain slices obtained from Wistar rats of different ages. 2. Although population field excitatory postsynaptic potentials (fEPSPS) are small in animals at postnatal day 10 (P10), both areas already exhibited short-term [posttetanic potentiation (PTP) and paired pulse potentiation (PPF)] and long-term [long-term potentiation (LTP)] plastic responses. 3. The amplitudes of the fEPSP and LTP increased with age in both regions, but peaked at P30 in CA3 while they were still increasing at the oldest age studied (P60) in CA1. In CA3, but not CA1, LTP at P60 was less than at P30. 4. PTP did not show clear alterations with age in either region. PPF decreased with age in CA1 but not CA3. PMID- 11775067 TI - Characterization of Hoxd1 protein-DNA-binding specificity using affinity chromatography and random DNA oligomer selection. AB - 1. Hoxd1 is member of the labial subfamily of Hox genes that has a conserved 60 amino acid homeodomain region. The homeodomain is an important determining factor in the binding of the protein to specific DNA sequence(s). DNA-binding specificity for the Hoxd1 protein has not been determined previously. 2. We have employed a rapid affinity chromatography method to determine optimal DNA binding sequences for the 109 amino acid Hoxd1 peptide, comprising the homeodomain and the entire carboxy terminal region of the Hoxd1 protein. 3. Labial Hox proteins have intrinsically weak DNA-binding activity that has been attributed to the nonbasic residues at positions 2 and 3 in the N-terminal arm of the homeodomain. The presence of the Hoxd1 carboxy terminal region negated the influence of the nonbasic residues and facilitated Hoxd1 DNA-binding specificity. 4. DNA sequences bound to the Hoxd1 peptide-affinity column were separated from a random pool of oligonucleotide sequences by gradient elution and enriched by polymerase chain reaction. Preferred sequences were identified on 5' and 3' of a TAAT core, extending the binding site to T/AT/gTAATTGTA. 5. Stability and specificity of optimal DNA-binding sequence for Hoxd1 homeodomain were determined by equilibrium and kinetic studies. Dissociation coefficient constant (KD) was estimated to be 8.6 x 10(-9) M and the DNA-Hoxd1 homeodomain complex has a half life (t(1/2)) of 12.7 min. 6. A molecular model of Hoxd1 homeodomain-DNA interaction based on the X-ray coordinates of Antennapedia homeodomain-DNA complex has revealed novel interactions of key Hoxd1 residues at the protein-DNA interface. PMID- 11775069 TI - Altered function of peripheral organ systems in rats exposed to chronic mild stress model of depression. AB - 1. In depression, psychiatric symptoms are frequently associated with impaired cardiovascular function and perhaps also increased risk for cancer diseases. Pathophysiological basis of this comorbidity is not clearly understood. Molecular events involved, particularly factors modified by chronic stress exposure, may only be evaluated in animal models of depression. 2. Present experiments were aimed to study parameters related to cardiovascular system (tyrosine hydroxylase (TH) gene expression in adrenal glands) and carcinogenesis (retinoic acid receptors in the liver) in the chronic mild stress model of depression. 3. Chronic mild stress induced a rise in adrenal TH gene expression in both male and female rats. Gender dependent changes were found in retinoic acid receptor binding with stress-induced activation in females but not males. Ovariectomized animals exhibited higher retinoic acid receptor binding. slightly elevated TH mRNA levels and failed to respond to chronic mild stress exposure with further increase in TH mRNA levels. Similarly, chronic mild stress induced an anhedonic state manifested by decreased sucrose preference in control but not ovariectomized rats. 4. Presented data document that central neurochemical and behavioral changes in animals exposed to chronic mild stress model of depression are associated with changes in adrenal TH gene expression and with gender dependent changes in retinoic acid receptor status in the liver. Such alterations may participate in the development of pathological changes and could participate on increased risk for cardiovascular and oncologic comorbidity in depressive patients. PMID- 11775068 TI - A potential role of central insulin in learning and memory related to feeding. AB - 1. Hypothalamic insulin (HI) is well known for its role in feeding regulation. In addition, its concentration is modified in response to meals. Recent studies suggest that brain insulin participates in memory processes, possibly through stimulation by glucose. 2. The present microdialysis study focused on local in vivo regulation of HI by glucose and on the effects of aging on HI, since aging is characterized by deterioration of memory, body weight regulation, and central glucose utilization. Glucose (8 mM) infused for 5 min increased extracellular HI levels rapidly, by 4.6-fold, and cerebellar insulin levels by 0.4-fold only, suggesting a specific area-dependent regulation of HI by glucose. Neither insulinemia nor glycemia were affected, suggesting a central mechanism. The same dose of glucose induced a modest (0.4-fold), delayed (45 min) increase in hypothalamic serotonin, suggesting that the effect of glucose on HI is independent of a previously defined local serotonin-induced insulin release. HI levels in old normal weight rats were half the levels of young rats. In genetically old obese (fa/fa) Zucker rats, HI concentration was 30% of that in young normal rats, suggesting a deterioration of HI availability when aging and obesity are combined. 3. The above results, in line with recent considerations on a potential role of central insulin in learning and memory, suggest particular effects of HI on feeding and memory and probably on a specific "memory for food." PMID- 11775070 TI - Fos protein expression in sacral spinal cord in relation to early phase of cauda equina syndrome in dogs. AB - 1. The aim of the present study is to map the incipient phase of Fos expression in the sacral spinal cord neuronal pools of multiple cauda equina constrictions canine model. 2. Fos-positive neurons were found bilaterally in the lateral portion of superficial dorsal horn layers (Laminae I-III) and along the lateral edge of the dorsal horn accompanied by the lateral collateral pathway, fibers of Lissauer's tract, terminating at the sacral parasympathetic nucleus. Similarly, high Fos expression was detected in the ventral portion of the dorsal sacral commissure and in the dorsomedial portion of the anterior horns at S1-S3 segment level. Finally, a clearly expressed Fos-positivity was disclosed bilaterally in the neuropil of the nucleus Y in the anterior horn. 3. Data from the present study show that continuous stimulation of the central fibers of sacral dorsal root ganglia neurons, i.e., fibers of sacral primary afferents, unlike those using various stimulations of the peripheral fibres offers an unusual pattern of Fos-like immunoreactivity. PMID- 11775071 TI - Establishment and partial characterization of a continuous human malignant glioma cell line: NG97. AB - 1. A human glioma cell line, NG97, was established from tissue obtained from a patient diagnosed with a grade III astrocytoma. 2. The NG97 cell line has been subcultured for more than 100 passages in standard culture media without feeder layer or collagen coatings. 3. NG97 cells grow in vitro as two subpopulations with distinct morphological appearance: stellate cells with pleomorphic nuclei, and small round cells with few processes. The cells have a doubling time of about 72 h and a plating efficiency of 1%. The injection of NG97 cells into congenitally athymic mice induced the formation of solid tumor masses that could be retransplanted every 4 weeks. The cells obtained from tumor mass when cultivated in vitro had a morphology comparable to those of the initial culture. 4. This cell line may prove useful for cellular and molecular studies as well as in studies of gliomas treatment. PMID- 11775073 TI - Peer influences on college drinking: a review of the research. AB - Peer pressure is consistently implicated in the excessive drinking of college students. However, both theory and empirical findings suggest that peer pressure is a combination of three distinct influences: overt offers of alcohol, modeling, and social norms. Overt offers of alcohol can range from polite gestures to intense goading or commands to drink. Modeling occurs when the student's behavior corresponds to another student's concurrent drinking behavior. Perceived social norms can serve to make excessive alcohol use appear common and acceptable to the student. This review critically examines the literature on each form of peer influence and provides suggestions for future research. PMID- 11775072 TI - trkB-receptor activation contributes to the kainate-induced increase in BDNF mRNA synthesis. AB - 1. The expression of brain-derived neurotrophic factor (BDNF) mRNA is induced by neuronal activity through increased intracellular calcium. As BDNF also increases intracellular calcium levels through trkB activation, we have examined here whether BDNF also regulates the synthesis of its own mRNA. 2. Neurotrophin mRNA expression was induced with kainic acid administration in transgenic mice overexpressing the dominant-negative form of BDNF receptor trkB and wild-type littermates. 3. Kainate strongly induced BDNF mRNA expression in both genotypes, but the up-regulation was significantly lower in transgenic mice. 4. These data suggest that the synthesis of BDNF mRNA is at least partly mediated by BDNF release and the activation of trkB receptors. The present findings further suggest that the BDNF signaling system in brain is regulated by positive feedback. PMID- 11775074 TI - Social approval and facilitation in predicting modeling effects in alcohol consumption. AB - PURPOSE: An important question for alcohol abuse prevention and treatment is whether individuals with high needs for social approval, or those who drink heavily in social contexts, are particularly vulnerable to modeling effects in alcohol consumption. METHODS: Male and female heavy social drinkers (N=202), as distinguished by these cognitive and situational variables, participated in a multisession dyadic modeling effects study along with a same-sex confederate model who exhibited alternating patterns of heavy and light consumption in an experimental barroom. RESULTS: Subjects with high needs for social approval, and those who tend to drink heavily in social contexts, were particularly vulnerable to imitating directional changes in modeled drinking levels across heavy and light consumption experimental sessions. Additionally, modeling effects were revealed, including reductions in drinking levels, regardless of individual characteristics such as demographics or levels of intoxication achieved on "usual drinking occasions." IMPLICATIONS: Findings suggest that individuals exhibiting high needs for social approval, and those who tend to drink heavily in social contexts, may benefit from (1) befriending lower risk models and (2) prevention and/or intervention efforts to reduce risk for substance use by reducing excessive needs for social approval and/or reducing exposure to social contexts where heavy drinking and related risk behavior is normative. PMID- 11775076 TI - What is the role of impression management in adolescent cigarette smoking? AB - PURPOSE: This study examined the role of impression management in cigarette smoking by linking the constructs of self-monitoring, perceived success in impression management, self-esteem and social anxiety among nonsmokers (NS), occasional smokers (OS), and frequent smokers (FS). METHODS: High school students (N=243) in years 8-12 completed a questionnaire assessing the above-mentioned variables. Multivariate discriminant function analysis and a priori contrasts were used to analyze the data. RESULTS: In comparison to OS, FS and NS had the lowest levels of self-monitoring, perceived success in impression management and self-esteem, while having the highest levels of social anxiety. IMPLICATIONS: Cigarette use may serve an impression management function during adolescence and subsequently influences OS' level of smoking. Intervention programs need to give greater consideration to providing adolescents with alternative strategies for both social acceptance and the acquisition and maintenance of self-esteem. PMID- 11775075 TI - Influence of depression and gender on smoking expectancies and temptations in alcoholics in early recovery. AB - PURPOSE: Rates of smoking are much higher among persons with alcohol problems and a history of depressive illness than persons without those disorders. Drug use in general may be motivated by outcome expectancies such as negative affective reduction and relaxation. Persons with a history of depression may smoke as a means of mood management. The role of outcome expectancies and major depression in maintaining smoking behavior in a high-risk group of smokers, such as recovering alcoholics, has not been thoroughly examined. METHODS: Using a cross sectional design, 161 abstinent alcohol-dependent men and women who smoked were administered the Inventory to Diagnose Depression (IDD), a self-report instrument for assessing current and lifetime depression according to DSM-IV criteria, and measures of alcohol dependence, nicotine dependence, smoking motives, and situation-defined temptations to smoke. RESULTS: As expected, smoking motives and temptations were moderated by history of depression. Alcoholics with a history of depression were more likely to smoke with the expectancy of negative affect reduction than those with no prior major depression. Using multiple regression, negative affective reduction, addiction, and severity of past depression were the strongest predictors of current temptations to smoke. IMPLICATIONS: These results suggest that individuals with a combined history of alcoholism and major depression are at a high risk to use smoking as a means of mood enhancement. PMID- 11775077 TI - Experimentally induced aggressive behavior in subjects with 3,4-methylenedioxy methamphetamine ("Ecstasy") use history: psychobiological correlates. AB - PURPOSE: Objective measures of experimentally induced aggressiveness were evaluated in 12 male 3,4-methylenedioxy-methamphetamine (MDMA, "Ecstasy") users, in comparison with 20 healthy male subjects. METHODS: All the subjects were preliminarily submitted to DSM-IV interviews and Buss-Durkee Hostility Inventory (BDHI). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money that was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Escape responses were also possible protecting the counter from monetary subtractions. RESULTS: Money earning responses were not different in Ecstasy users and controls; aggressive responses were significantly higher in Ecstasy users in comparison with control subjects (F=20.74, P<.001). Baseline adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were higher in Ecstasy users than in controls. No difference was found in norepinephrine (NE) and epinephrine (EPI) basal levels of the two groups. During the experimentally induced aggressiveness, plasma ACTH concentrations increased significantly less and NE and EPI levels, together with heart rate (HR), increased significantly more in Ecstasy users than in healthy subjects. Despite ACTH-blunted responses, CORT did not increase differently from controls in Ecstasy users. PSAP aggressive responses positively correlated with catecholamines and CORT changes, BDHI Direct Aggression and Irritability scores, both in Ecstasy users and controls. A significant correlation was found between Ecstasy exposure extent and aggressive responses (r=.78, P<.001). IMPLICATIONS: Our findings suggest that Ecstasy users have higher outward-directed aggressiveness than healthy subjects. Aggressiveness in MDMA subjects seems to be associated more with MDMA pharmacological effects than with personality traits: Nevertheless, a premorbid psychobiological proneness to aggressive behavior cannot be excluded. Increased catecholamines reactivity, basal hypothalamus pituitary-adrenal (HPA) axis hyperactivity, and blunted ACTH responses could be due to MDMA action on monoaminergic pathways and adrenal function. PMID- 11775078 TI - Age at onset of alcohol use and DSM-IV alcohol abuse and dependence: a 12-year follow-up. AB - PURPOSE: The purpose of this study was to examine the relationship between age at drinking onset and the development of DSM-IV alcohol abuse and dependence in a 12 year prospective study of youth in the United States. METHODS: Logistic regression analyses were used to quantify the relationship between age at drinking onset and the development of alcohol abuse and dependence controlling for sociodemographic factors and problem indicators. RESULTS: The odds of alcohol dependence decreased by 5% in 1989 and 9.0% in 1994 for each year drinking onset was delayed. In 1994, the odds of alcohol abuse increased by 7.0% with each decreasing year of age at drinking onset, while age at drinking onset was not related to alcohol abuse in 1989. Several other risk factors were found to be strong and consistent predictors of abuse and dependence in 1989 and 1994, including being male, divorced, separated or never married, younger, and having an early history antisocial behaviors and marijuana use. IMPLICATIONS: Implications of the results of this study are discussed in terms of other factors that may impact on the onset-abuse and onset-dependence relationship and the need to focus future prevention efforts. PMID- 11775079 TI - Do companions of designated drivers drink excessively? AB - PURPOSE: A common criticism of designated driver programs (DDPs) is that they promote excessive drinking among companions of the designated driver (DD). METHODS: Data were collected from two representative samples of drinkers using computer-assisted telephone interviews (CATIs), and questionnaires administered to customers in barrooms. RESULTS: Most respondents drank moderately--had usual estimated blood alcohol concentrations (BACs) of less than 0.10 when they used DDs. Differences between respondents' estimated BACs when they used a DD and when they drank outside their homes were very small: 0.017 in both samples. Additional analyses examined shifts between lower and higher categories of risk defined as a BAC of less than 0.10 and a BAC of 0.10 or greater. A minority, 15% of CATI and 30% of barroom respondents, switched to the higher risk category when using a DD. These CATI and barroom respondents increased their BACs by an average of 0.089 and 0.11, respectively. Risk associated with this increase was mitigated, however, by respondents' infrequent use of DDs. IMPLICATIONS: Use of DDs was not generally associated with excessive alcohol consumption. Since a minority of respondents did drink heavily when using a DD, programs promoting DD use should caution drinkers that the availability of a DD is not an excuse for excessive consumption, and remind hosts and servers that they should not overserve their guests or customers even when they have a DD. PMID- 11775080 TI - Sexual assault and alcohol abuse: a comparison of lesbians and heterosexual women. AB - PURPOSE: To compare and contrast lesbians' and heterosexual women's experiences of sexual assault and to investigate relationships between sexual assault and alcohol abuse. METHODS: In-depth interviews were conducted with 63 lesbians and a demographically matched comparison group of 57 heterosexual women. Lesbians' and heterosexual women's experiences of sexual assault, drinking levels, and alcohol abuse indicators were compared using descriptive statistics. LISREL analysis was used to test the effects of sexual assault on a latent measure of alcohol abuse. RESULTS: Lesbians reported more childhood sexual experiences, were more likely to meet the study definition for childhood sexual abuse (CSA), and were more likely to perceive themselves as having been sexually abused as children. CSA was associated with lifetime alcohol abuse in both lesbian and heterosexual women. However, adult sexual assault (ASA) was associated with alcohol abuse only in heterosexual women. IMPLICATIONS: Sexual assault is a common experience among both lesbians and heterosexual women. Findings emphasize the importance of asking about sexual assault in health histories, and assessing clients for substance abuse and other sequelae of sexual assault. PMID- 11775081 TI - Change in psychosocial functioning and social relations among women in residential substance abuse treatment. AB - PURPOSE: The purpose of this study was to examine the degree to which psychosocial functioning and social relationships changed during the first 3 months of treatment among women in a residential substance abuse program that emphasizes the importance of developing healthy relationships. METHODS: Participants included 77 female clients admitted to the Salvation Army First Choice (FC) Program in Fort Worth, TX. Assessments of psychological functioning, family relations, and peer relations were administered at treatment entry and again after 3 months. Relationships with clients in treatment and friends outside treatment were measured separately. RESULTS: Repeated-measures analyses of variance (ANOVA) indicated that interpersonal relationships improved. Family networks increased, family cohesion increased, and family conflict decreased. Peer networks changed as well, due in part to new relationships with other clients in treatment. The number of drug-using friends decreased, peer deviance and negative influence decreased, and social conformity among friends increased. There was a corresponding improvement in psychosocial functioning. IMPLICATIONS: Results suggested that relationship-centered treatment for women was effective. Clients reestablished connections with family members, disassociated from drug using peers, and improved the quality of relationships with family members and friends. Further research is needed in order to examine the influence of specific treatment components and the potential long-term effects of changes in women's relationships. PMID- 11775082 TI - Cigar risk perceptions in focus groups of urban African American youth. AB - PURPOSE: To explore cigar use perceptions among urban African American youth. METHODS: A convenience sample (n = 50) of African American volunteer participants, ages 14- 18, participated in six audiotaped focus groups conducted in two California cities. Transcriptions were analyzed using iterative strategies. RESULTS: Most youth believed cigars were harmful to health, yet a disjuncture existed between this abstract belief and the socially embedded understandings revealed in discussions. Some youth felt that cigars were more "natural" and therefore less harmful than cigarettes. For some, that understanding rested on a mistaken assumption that nicotine was an artificial additive not present in cigars. Youth had received little cigar-specific health education. They reported that cigars were easily obtained, noted cigars' social cachet, and drew attention to new brands targeting youth. IMPLICATIONS: Perceptions of risk are not merely interesting "subjective" findings but are important determinants of actual use patterns and may not correlate with abstract beliefs. Recent cigarette brand repositionings, such as Winston's "no additives" campaign, have widely publicized the many substances added to cigarettes. Some youth may take lack of cigar-specific preventive education as an indication that cigars do not contain such substances, including nicotine. Misperceptions about risks of cigar and cigar/marijuana smoking must be addressed through consistent, coordinated, and comprehensive tobacco control efforts for all tobacco products. PMID- 11775083 TI - Gender differences in the association of alcohol intoxication and illicit drug abuse among persons arrested for violent and property offenses. AB - PURPOSE: To explore the associations between violent and other crimes, and alcohol intoxication and recent use of cocaine, marijuana, and other drugs among men and women arrestees and examine gender differences in these relationships. METHODS: We conducted a secondary analysis of 1998 using Arrestee Drug Abuse Monitoring (ADAM) system data using a sample of 9242 male and 2594 women arrested for violent and property offenses in 35 cities. Logistic regression was used to predict arrest for a violent offense (rather than a property crime) from drug- and alcohol-related, and other variables. RESULTS: Both gender and alcohol intoxication are significantly related to arrest for a violent offense. However, the intoxication effects (in the absence of cocaine) are more than three times as great for female (Exp(beta) = 5.59) as male arrestees (Exp(beta) = 1.74), while the combined effects of alcohol and cocaine predict a property offense for women but are insignificant for men. IMPLICATIONS: To achieve further reductions in violent crime, intervention strategies need to focus on reducing alcohol intoxication as well as illicit drug use. Research on the role of alcohol on women's aggression and violence also is suggested. PMID- 11775084 TI - Tobacco smoking in marijuana-dependent outpatients. AB - PURPOSE: Among marijuana-dependent individuals, approximately 50% smoke tobacco. These individuals are exposed to increased risks of respiratory and other health problems. The current study examined whether tobacco smoking among marijuana dependent individuals is also associated with increased psychosocial and substance abuse problems. METHODS: Marijuana-dependent individuals (N=174) seeking treatment for marijuana problems completed a 2-3 h assessment. Current tobacco smokers were compared to ex-smokers and never smokers on demographic, psychosocial, and substance use characteristics, and treatment outcome. In addition to univariate comparisons, multivariate analyses using multinomial logistic regression were conducted to control for the correlated nature of the predictor variables. RESULTS: Current tobacco smokers earned less income and reported histories of more alcohol problems than never smokers and had fewer years of education, more legal problems, more psychiatric symptoms, and an earlier age of marijuana initiation than ex- and never smokers. Over the course of treatment, current tobacco smokers had significantly fewer marijuana-negative urine specimens and fewer weeks of continuous marijuana abstinence than ex smokers. IMPLICATIONS: Current tobacco smokers appear to represent a subgroup of marijuana-dependent individuals who have increased psychosocial problems compared to ex- and never smokers and may not respond as well to treatment than ex smokers. PMID- 11775085 TI - Prediction of DISC substance abuse and dependency for ethnically diverse adolescents. AB - PURPOSE: This study examines the validity of selected items from the Substance Abuse Subtle Screening Inventory-Adolescent (SASSI-A) version in predicting Diagnostic Interview Schedule for Children (DISC version 2.3) Substance abuse and dependency (SA/D) for Native Hawaiian (i.e., indigenous people of the Hawaiian Islands) and non-Hawaiian adolescents (youth without any Native Hawaiian indigenous ancestry). METHODS: 542 students were randomly selected from the larger sample to participate in the DISC administration. Demographic information, SASSI-A scores, and DISC diagnoses were obtained for each student. Univariate and multiple logistic regressions were performed in the prediction of DISC SA/D. RESULTS: SASSI-A Factor 1, consisting of three items measuring substance use, was found to have the best utility, accounting for 18.1% of the variance, in predicting DISC SA/D. IMPLICATIONS: These results support selected SASSI-A items in screening for SA/D for Native Hawaiian and non-Hawaiian adolescents in Hawaii as compared to other community-based screening instruments for other populations. PMID- 11775086 TI - Rural-urban differences in the distribution of parent-reported risk factors for substance use among young adolescents. AB - PURPOSE: We examined rural-urban differences in cumulative risk for youth substance use. A recent report [National Center on Addiction and Substance Abuse (CASA) 2000] found that the rural-urban distribution of substance use and known risk factors for substance use differed; in many cases rural youth showed higher levels of use, as well as higher levels of risk factors. The current investigation, while not directly examining substance use, further examined rural urban differences in the distribution of risk factors for youth substance use, based on information from parent reports. METHOD: Study 1 data were collected from a random sample of Midwestern parents (n = 339) with a young adolescent between the ages of 11 and 13 years. Study 2 data were collected from a second sample of Midwestern parents (n = 593). RESULTS: Analyses of rural-urban comparisons demonstrated higher levels of cumulative risk among rural youth. An evaluation of the sensitivity of the analysis to rural-urban classification schemes indicated that the findings were robust, but that there was some minor variation in rural-urban differences by classification scheme. IMPLICATIONS: Results contribute to an explanation of findings from earlier reports of rural urban differences in substance use, and suggest directions for future research on rural-urban distributions of youth risk factors. PMID- 11775087 TI - Characterizing the ideal antidepressant therapy to achieve remission. AB - A paradigm shift in the management of depression has transpired in recent years with the modification of treatment goals toward remission, an outcome that transcends response. Pharmacotherapy, psychotherapy, electroconvulsive therapy, and combination therapies are treatment modalities available to the clinician for facilitating remission in depressed patients. For patients with moderate-to severe depression, pharmacotherapy, either alone or in combination with other therapeutic approaches, is the treatment of choice. Antidepressants have heterogeneous effects on neurotransmitter systems that are manifested in different levels of selectivity and potency, influencing the drugs' safety profile through their potential for inducing drug-drug interactions. In terms of the pharmacokinetic-pharmacodynamic characteristics of antidepressants, a positive dose-response relationship has been shown to enhance the achievement of full remission because it allows the clinician to maximize drug dosage to optimize efficacy. Evidence from several studies indicates that treatment strategies that involve combined serotonergic and noradrenergic mechanisms result in pharmacologic synergism that leads to an enhanced antidepressant effect. This article identifies key characteristics of antidepressants that have been associated with greater efficacy. PMID- 11775088 TI - Clinician perspective on achieving and maintaining remission in depression. AB - The majority of large-scale clinical trials of depression focus on response, typically defined as a 50% reduction in symptoms, as the endpoint. Response in the absence of remission places patients at greater risk for relapse, decreases their level of functioning, and erodes quality of life. Most importantly, both research and our clinical experience suggest that remission, or "getting well," is an attainable goal for patients with major depressive disorders. Pharmacotherapy, psychotherapy, and combination regimens are all treatment options. Recent studies across a range of patient populations have demonstrated the benefit of affecting multiple transmitter systems over a single antidepressant mechanism. Pooled data from more than 2000 patients comparing venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and selective serotonin reuptake inhibitors suggest that the dual mechanism of action of venlafaxine provides significantly greater efficacy in achieving remission. Ultimately, achieving a good clinical outcome is desirable, but sustaining the mood state is, perhaps, more important. Studies of venlafaxine show it is possible to prevent more relapses and recurrences of depression with dual mechanism treatment than with placebo. These data highlight the need for setting appropriately aggressive goals and working closely with our patients to achieve them. By doing so, we create the best opportunity for restoring patients to "wellness" and, ultimately, a normal and fulfilling life. PMID- 11775089 TI - Depression and quality of life: a patient's perspective. PMID- 11775090 TI - Met and unmet needs in the management of depressive disorder in the community and primary care: the size and breadth of the problem. AB - Numerous epidemiologic studies have revealed the high prevalence of depressive disorders despite the availability of several treatment options that have been proved to be efficacious and safe. The persistence of depression, at a time when treatment options have increased, suggests that there are unmet needs in the clinical management of depression. Aside from improving treatment guidelines, the role of primary care physicians should be redefined to ensure that lifetime depressive disorders are more frequently recognized, diagnosed, and appropriately treated and managed, either by these clinical "gatekeepers" or through referrals to mental health specialists. With this management strategy, access to care can be broadened to include not only the severely ill, but also patients in earlier stages of their depressive illness process who might profit most from modern treatment methods. PMID- 11775091 TI - New standard of depression treatment: remission and full recovery. AB - Major depressive disorder (MDD) is a chronic disorder that substantially impairs a patient's psychosocial and occupational functioning. Lifetime prevalence rates for MDD vary widely, ranging from 4.4% to approximately 20%, and it is predicted to become the second leading cause of disability by the year 2020. The magnitude of this public health problem, with its associated decreased quality of life, increased risk of suicide, loss of productivity, and increased health care use, underscores the importance of treating depressed patients to full remission. The presence of residual depressive symptoms due to partial or incomplete remission is associated with significant morbidity and mortality. Hence, complete remission should be the goal in the treatment of patients with MDD because it leads to a symptom-free state and a return to premorbid levels of functioning. Full remission and improved long-term prognosis can be achieved with long-term antidepressant therapy with newer agents that work through multireceptor mechanisms, especially through the serotonergic and noradrenergic systems (i.e., dual action). Robust efficacy and greater remission rates have been associated with dual-action agents. PMID- 11775092 TI - In-pouch TV culture system in diagnosis of Trichomonas vaginalis infection. AB - A newly simplified culture method, the In-Pouch TV culture system, the wet mount (WM) examination and the acridine orange stain were compared with the Oxoid culture as a standard technique in the diagnosis of trichomoniasis. Out of 70 symptomatic cases enrolled in this study, 28 specimens were positive by all methods. Among these positive specimens, 21 were positive by the Oxoid culture (75%) and 24 (85.7%) with sensitivity of 85.7% by the In-Pouch system. Both wet mount preparation and acridine orange stain had less sensitivity than the In Pouch system (61.9%) and detected 15 (53.6%) and 16 (57.1%) of the cases respectively. The In-Pouch system has been proved to be easier in the transport and culture technique than the ordinary culture method. It alleviates the need to enter the culture, thus prevents contamination. Its cost is comparable to the ordinary culture tube. Therefore, it is recommended to use the In-Pouch culture system as a method of diagnosing trichomoniasis. PMID- 11775093 TI - In vivo, attenuation of schistosome cercarial development and disturbance of egg laying capacity in Biomphalaria alexandrina using sublethal concentrations of plant molluscicides. AB - The dry powdered of Sinapis arvensis, Thymelaea hirsuta, Callistemon lanceolatus and Peganum harmala showed molluscicidal activity against Biomphalaria alexandrina, specific intermediate hosts to Schistosoma mansoni. Effect of LC25 of dry powdered plant molluscicides on hexokinase (HK), glucose phosphate isomerase (GPI), AMP deaminase, adenosine deaminase and phenol oxidase (PO) of B. alexandrina was traced. C. lanceolatus showed the highest molluscicidal activity as it has the lowest LC50 compared to S. arvensis, T. hirsuta, and P. harmala. LC25 of the latter three plants resulted in more significant inhibition of HK, GPI, AMP-deaminase and PO than C. lanceolatus. Treatment of snails with LC10 of these plants markedly affected compatibility of B. alexandrina to S. mansoni infection. Significant decrease in cercarial production recorded in snails treated with sublethal concentrations of S. arvensis, T. hirsuta, and P. harmala. Remarkable impairment of the egg laying capacity of molluscicide-treated snails was also recorded. Correlation between activity levels of HK, GPI and AMP deaminase and compatibility to parasitic infection and role of PO in the egglaying capacity of these snail species were discussed. PMID- 11775094 TI - The effect of changes in the gastric pH value on experimental trichinosis. AB - The effect of increasing or decreasing the gastric pH of mice on the course of experimental infection with Trichinella spiralis was studied, by administration of 1% NaHCO3 in PBS (pH 9.0) or 1% HCl in PBS (pH 5.0) to mice half an hour prior to infection respectively. The results revealed that raising the gastric pH led to a significant increase in the adult worm count with all increase in their fecundity both in vivo and in vitro. On on the other hand, the more acidic gastric pH induced prior to infection led to its amelioration. This was obvious by the significant reduction in the adult worm count and their inability to give birth to newborn larvae. Several factors may be incriminated, among which are decreased larval infectivity and affection of the maturation of the reproductive organs, mainly the uterus and the testis. Changes in their morphology were observed by both light and transmission electron microscopic studies, which could account for the impairment in their functions, namely embryogenesis and spermatogenesis. PMID- 11775095 TI - Laboratory assessment of the molluscicidal activity of Commiphora molmol (Myrrh) on Biomphalaria alexandrina, Bulinus truncatus and Lymnaea cailliaudi. AB - The molluscicidal properties of the oil extract of Commiphora molmol (Myrrh) were tested against Egyptian snail species: Biomphalaria alexandrina, Bulinus truncatus and Limnaea cailliaudi. The impact of the extract on the egg cluches of B. alexandrina and L. cailliaudi was also evaluated. Snails and their eggs were exposed for 24 and 48 hr at 22-26 degrees C to various concentrations of the extract. The results showed different susceptibilities B. alexandrina showed higher LD50 and LD90 (155, 195 ppm) than B. truncatus (50, 95 ppm) and L. cailliaudi (50, 85 ppm) after 24 hr exposure. 100% mortality was obtained for the egg cluches of B. alexandrina and L. cailliaudi at concentrations of 100 ppm and 75 ppm respectively. Lower concentrations were needed to obtain the same results after 48 hr. The present laboratory studies demonstrated that Myrrh has a molluscicidal effect on the snail intermediate hosts, particularly on their eggs. Field studies are recommended. PMID- 11775096 TI - Evaluation of soluble adhesion molecules in the diagnosis of amoebiasis, giardiasis and toxoplasmosis. AB - A total of 47 patients with toxoplasmosis (21 cases) with amoebic liver abscess (14 cases) and with giardiasis (12 cases) as well as 14 healthy control were subjected to thorough history taking, clinical examination, stool & urine analysis, complete blood picture, ESR, C-reactive protein, ASO, widal test, blood cultures, liver function tests, serum creatinine, hepatitis viral markers, rheumatoid factor, auto-antibodies, stool culture, rectal snip, chest X-ray, abdominal sonar, level of serum adhesion molecules (sICAM-1, sELAM-1), ELISA detection of Toxoplasma antibodies in serum, liver biopsy, detection and counting of Giardia cysts. In toxoplasmosis group, highly significant increase in serum levels of sICAM-1 (P<0.01) and significant increase in serum levels of sELAM-1 (P<0.05) in comparison to control. However, only sICAM-1 levels were significantly increased in IgM cases more than in IgG cases. In amoebic liver abscess group, both sICAM-1 and sELAM-1 significantly increased when compared with control. In giardiasis group, highly significant increase of serum levels of sELAM-1 was noticed than in control group (P<0.01), while sICAM-1 showed no significant difference (P>0.05). There was no correlation between sELAM-1 and number of cysts in the stool (intensity of infection). Soluble forms of adhesion molecules especially sICAM-1 have the potentiality as good markers of endothelial damage, severity of disease and to less extend load of infection. PMID- 11775097 TI - Potency of three Haemonchus contortus antigens in the diagnosis of ovine haemonchosis. AB - One hundred faecal specimens and corresponding blood samples were evaluated for Haemonchus contortus infection in sheep by ELISA utilizing somatic, circulating and coproantigens. Results proved that coproantigen was more potent than the others in diagnosis of sheep haemonchosis. SDS-polyacrylamide gel electrophoresis demonstrated that the three antigens are structurally related. Immunoblot analysis revealed that somatic antigen contained 6 polypeptides of molecular weights 234, 205, 178, 83, 48 and 14 kDa, while, coproantigen showed 4 immunogenic polypeptides of 234, 205, 85 and 45 kDa. In circulating antigen only 2 polypeptides of molecular weights 165 and 99 kDa were immunoreactive. The potency of coproantigen may be attributed partially to one polypeptide of molecular weight 45 kDa. This low molecular weight polypeptide was only expressed in coproantigen as an immunogen, probably increases the immunogenicity, and may have potential diagnostic and protective values. PMID- 11775098 TI - Potential effect of Allium cepa and Allium sativum on haemolymph of Biomphalaria alexandrina, the intermediate host of Schistosoma mansoni. AB - Biomphalaria alexandrina were fed on either Allium cepa or A. sativum to study their effects on some biochemical parameters such as total proteins, free amino acids and liver enzymes (ALT, ALP and AST) on egg laying activity of the snails. The results revealed that ALP was highly significantly reduced in haemolymph of snails that fed on either Allium cepa or A. sativum. Also, ALT and AST were highly significantly reduced in haemolymph of snails that were fed on A. cepa while those fed on A. sativum showed no change in ALT activity and a high significant increase in AST activity. Total proteins were significantly decreased in haemolymph of all treated snails whereas variations in free amino acids contents were also observed. The reproductive activity of snails fed on either Allium cepa or A. sativum was highly affected. In addition, growth rate of newly hatched snails fed on either A. cepa or A. sativum was affected. Exposure of snails to water containing either A. cepa or A. sativum caused snail toxicity which may result from alterations in the snails' habitat. PMID- 11775099 TI - Clinico-epidemiological study of human fascioliasis in an endemic focus in Dakahlia Governorate, Egypt. AB - Human fascioliasis is increasing in the Nile Delta particularly in Dakahlia Governorate, where it reached 7.47%. In this study, the tetrad of fascioliasis was established as high eosinophilia (100%), fever (85.6%), painful hepatomegaly (81.93%) and anaemia (100%). The laboratory results showed ESR accelerated in 87%, ALT elevated in 21.5%, AST elevated in 21.9%, S. bilirubin elevated in 16.5%, gamma GT elevated in 80.6%, and SAP elevated in 76.4%. Abdominal ultrasonography showed variable findings, as hepatomegaly, splenomegaly, periportal fibrosis, thickened wall of gall bladder, dilated common bile duct, dilated biliary radicals (partial), dilated common bile duct and biliary radicals (total), Fasciola worms in gall bladder, Fasciola worms in common bile duct, stones in gall bladder, stones in bile duct, cystic lesions in the liver, local lesions in the liver and ascitis. The highest was hepatomegaly in 81.93% of fascioliasis patients and the lowest was biliary dilated radicles (partial) in 0.26%. PMID- 11775100 TI - Rodents and their ectoparasites in Wadi Hanifah, Riyadh City, Saudi Arabia. AB - A survey was conducted on commercial and wild rodents from different locations in Wadi Hanifah in Riyadh. Six species of rodents were collected with wire net traps baited with fresh cucumber or fatty cheese. The trapped rodents in descending order of numbers were Rattus rattus rattus, Acomys dimidiatus, Meriones libycus, R. r. frugivorus, R. r. alexandrinus and Mus musculus. The ectoparasites were a flea, Xenopsyllus sp. on R. r. frugivorus and a tick, Rhipicephalus turanicus on each of A. dimidiatus and R. r. alexandrinus. In general, rodents and ectoparasites were low in Wadi Hanifah, probably due to the severe hot and very dry weather mainly in the summer season. PMID- 11775101 TI - IL-10 gene expression as a marker for detection of protective immunity levels with irradiated cercarial vaccine against experimental Schistosoma mansoni infection. AB - Cercariae were obtained in a large number from the maintained life cycle of S. mansoni. They were attenuated at different doses (20 Kr, 50 Kr, 60 Kr, 70 Kr and 80 Kr) of gamma radiation. Laboratory bred Swiss Albino mice were classified into 7 groups. Five groups were immunized with +/-500 S. mansoni cercariae. Two groups were used as positive and negative controls. All animals were sacrificed after 8 weeks. Spleen cell proliferative responses to Phytohaemagglutinin (PHA) were assessed in all groups. IL-10 was measured by ELISA in serum and splenic cells secretion in-vitro. RNA extracted from freshly isolated liver cells was analyzed for detection of mRNA of IL-10 by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed augmentation of proliferative cell from the spleen in all vaccinated groups except with 80 Kr, irradiated cercariae group. The highest percentage of lymphocytes transformation was recorded among the mice immunized with 60 Kr, irradiated cercariae. After challenge, splenic responses in all groups declined progressively to the control level. IL-10 secretion from spleen cells of all vaccinated groups increased after challenge with the least level in 60 Kr, immunized challenged group. IL-10 mRNA expression was higher among 60 Kr, immunized with irradiated cercariae mice group than 70 Kr, one, but with no expression among 80 Kr, cercariae immunized ones. PMID- 11775102 TI - Soluble adhesion molecules versus lymphoblast transformation in diagnosis of zoonotic cutaneous leishmaniasis. AB - Twelve parasitologically proven ZCL patients (one with non-ulcerative lesion and eleven with multiple ulcerative lesions) were subjected to estimation of the levels of lymphoblast transformation (LTT) and soluble adhesion molecules (sICAM 1 & sELAM-1 by ELISA). The results proved high percentage of LTT in relation to number and clinical picture of the ZCL lesions. As to the soluble adhesion molecules, sICAM-1 levels were significantly increased than in normal controls and correlated positively with the number of ulcerative lesions. sELAM-1 levels were not significantly increased than the normal controls, but correlated positively with the number of ulcerative lesions. Consequently, soluble adhesion molecules mainly sICAM-1 is a good marker of endothelial damage in ZCL as related to number and clinical type of lesions. PMID- 11775103 TI - Effect of midgut bacteria of Culex pipiens L. on digestion and reproduction. AB - An investigation was carried out to evaluate the influence of symbiotic bacteria associated with Culex pipiens L. on pre-oviposition and blood meal digestion periods, and reproductive potential (fecundity and fertility). Aposymbiotic females were obtained by feeding the normal females on 10% sucrose solution mixed with antibiotic (Tarivid) for three days before feeding them on normal blood meals from a pigeon host. A total of 4 genera were previously isolated from the midgut of C. pipiens. These genera were: Bacillus, Streptococcus, Staphylococcus, and Salmonella and Shigella. It seems that the period of blood meal digestion preceded the pre-oviposition period of both bacterial free females and bacterial free females treated with one of the aforementioned bacteria. In addition, it is obviously clear that, the presence of the two bacterial genera: Bacillus and Staphylococcus in the midgut of C. pipiens is essential for normal and high fecundity. Generally, it is evident that the symbionts (gut bacteria) are essential for the completion of embryonic development. PMID- 11775104 TI - Is the intestinal tract a portal of entry for Acanthamoeba infection? AB - Acanthamoeba culbertsoni isolated from a water sample of El-Mahmoudia canal in Alexandria, was orally inoculated into a mouse model (200-400 amoebae/mouse) under different conditions. One week postinfection (P.I.), 20% of infected normoacidic mice and all animals received cimetidine or tetracycline prior to infection passed the parasite in their stools. One month P.I., 70% of cimetidine and 100% of tetracycline pretreated mice showed marked erosion in the intestinal mucosa and areas of necrosis with congestion in the brains, with trophozoites and cysts in both tissues. It is concluded that, normoacidic mice may be simply acting as paratenic hosts. In case of hypoacidity or altered normal flora, the intestinal tract was invaded by amoebae representing a new portal of entry for CNS infection. PMID- 11775105 TI - Efficacy of flumethrin and coumaphos against the camel tick Hyalomma dromedarii L. (Acari: Ixodidae). AB - The efficacy of Flumethrin pour on and Coumaphos 50% WP was tested against different stages of Hyalomma dromedarii. With contact method, LC50 values for larvae and adults were 0.04, 0.03 ug/cm2 and 0.05, 1.06 ug/cm2 respectively. The LC50 for coumaphos against the larvae, adults and eggs using dipping method were 44, 63, and 62 ppm respectively. Flumethrin caused significant reduction in oviposition and hatchability in female ticks that survived sublethal concentrations, while sublethal doses of coumaphos had no effect on the reproductive potential of the tick. The results showed that flumethrin was 8 times more toxic than coumaphos. PMID- 11775106 TI - Genetical and electron microscopical studies on Cryptosporidia. AB - The present work was to clarify whether C. parvum oocysts have different strains in human patients by using different staining, electron microscopical and genetical techniques. A trial to induce a vaccine against Cryptosporidial infection in mice was carried out using killed autoclaved Cryptosporidial oocysts. The results obtained were satisfactory. Two genotypes of C. parvum, viz: human and zoonotic genotypes were detected and described. The killed vaccine used orally gave a promising results. PMID- 11775107 TI - Study on the effect of Bacillus thuringiensis (B.t. serotype H-14) and its toxins against Cephalopina titillator (Clark), the Egyptian camel myiasis producing dipterous fly. AB - Bacillus t. israelensis (B.t. serotype H-14) and its toxins have a marked lethal effect on both the eggs and the newly moulted 3rd stage larvae of Cephalopina titillator. The Bacillus was less effective than Bacillus and its toxins on both the eggs and larvae. On the other hand, the larvae were more affected by both Bacillus and Bacillus and its toxins than the eggs. Prolonged exposure time showed more lethal effect. PMID- 11775108 TI - Coccidiosis among immuno-competent and -compromised adults. AB - There was significant increase in coccidia positive cases among Hodgkin lymphoma receiving chemotherapy as compared to control group (p < 0.05). The increase was highly significant in the group of acute lymphocytic leukaemia receiving chemotherapy as compared to control group (P < 0.01). The total percent of cases with single type of coccidia were 12.2% compared to multiple coccidial infections (4.3%). The most commonly associated parasite was Cryptosporidium. The total cryptosporidial infections (single and mixed with other coccidia) were 12.1% of the total studied cases. In the immunocompromised the prevalence was 14.3%. In the immunocompetents with diarrhoea, was 8.3% and in control was 5.6%. Microsporidial infections (single and mixed with other coccidia), being the least detected among the four intestinal spores forming coccidia, were 2.4% in the immunocompromised groups. No Microsporidium was detected in the immunocompetent or adult control groups. The total cyclosporal infections (single and mixed with other coccidia) were 6.3% of the total studied cases. In the immunocompromised groups, the prevalence was (8.3%) where in immunocompetent group, was 2.8%. None was detected in the control subjects. Single cyclospora was 3.0% while mixed Cyclospora represented 3.3% of all studied cases. The Isospora infections (single and mixed) were 3.8% of total patients. The prevalence among immunocompromised group was 5.2% and in immunocompetent patients was 2.8%. PMID- 11775109 TI - Thoracoscopic sympathectomy for treatment of hyperhidrosis surgical experience and results of 30 cases. AB - The thoracoscopic sympathectomy in treatment of primary palmar and axillary hyperhidrosis was performed on 30 patients complaining of hyperhidrosis admitted to El Demerdash University Hospital and Ain Shams University Specialised Hospital and The Saudi German Hospital between March 1999 and March 2001. The indication of surgery was primary palmar hyperhidrosis in 24 cases and combined palmar and axillary hyperhidrosis in 6 cases. 25 cases were males and 5 cases were females. The mean age in our sample was 25.7 +/- 4.05 years. There were no major complications in our series and 4 cases were complicated by intercostal vessels bleeding which were successfully controlled by cauterization during surgery and no one of them necessitated neither thoracotomy nor application of intercostal tubes. The patients were followed up for one year after operation and only one case had recurrence of palmar hyperhidrosis. PMID- 11775110 TI - Studies on the molluscicidal and larvicidal properties of Solanum nigrum L. leaves ethanol extract. AB - Toxicological studies on three ethanol extract preparations of Solanum nigrum L. leaves were made on Biomphalaria alexandrina. Extract (A), made by soaking leaves powder over night in cold 70% ethanol, has the highest activity, (LC50 3.37 mg/L within 24 hr). This extract also showed larvicidal activity against larvae of two mosquito species, Aedes caspius and Culex pipiens, (LC50 51.29 and 125.89 mg/L within 24 hr, and 21.38 and 38.11 mg/L within 48 hr, respectively). Sunlight, pH, and turbidity did not affect the activity of this extract, but the molluscicidal activity seems to be correlated with the increase of temperature. The concentrated extract (1000 mg/L) can be stored at room temperature for six months without any change in its activity, but diluted solutions of this extract lost their activity after four weeks. PMID- 11775111 TI - Prophylactic efficacy of recombinant IL-12, clindamycin alone or in combination against experimental reactivated toxoplasmosis. AB - Reactivation of experimental chronic toxoplasmosis was induced by daily i.m. injection of 0.1 ml hydrocortisone acetate (25 mg/ml) per mouse. Administration of clindamycin (5 mg/kg orally), rIL-12 (0.25 microg i.p.) or combination of both was done once weekly for 3 months course starting 2 days post suppression. The prophylactic effect was assessed by determination of both survival rate and brain cyst counts with histopathological examination of brain sections at different time points post suppression besides the influence of these drug regimens on interferon gamma (IFN-delta) production. All immunocompromised untreated mice exhibited increased brain cyst burdens and reduced IFN-delta production and died due to toxoplasmic encephalitis. Neither clindamycin nor rIL-12 prevented reactivation of chronic infection, however, the slight prolongation of survival was observed. Simultaneous administration of clindamycin and rIL-12 resulted in prevention of reactivation in 73.3% of the mice till the end of the experiment. The combination regimen produced significant higher levels of IFN-delta than either drug alone suggesting that both rIL-12 and clindamycin can act additively or synergistically to prevent reactivation of chronic infection with T. gondii most probably through enhancement of IFN-delta production. PMID- 11775112 TI - The pathogenesis of Demodex folliculorum (hair follicular mites) in females with and without rosacea. AB - In rosacea patients (ages 11-50 years old) 44% were infested with D. folliculorum as compared to normal controls (23.0%). The difference was significant. The mean +/-SD of mite density ranged between 13.2+/-0.9 to 18.2+/-1.2 as compared to normal controls with mite density ranged between 1.4+/-0.25 to 2.4+/-0.3. Demodex infestation in rosacea patients was 66.1% in squamous, 66.7% in erythemato telangiectate and 83.3% in papulo-pustular rosacea. The highly infested site was check (27.3%) with mean mite density of 25.3+/-1.3, followed by the area around the orbit (23.4%) with a density of 19.0+/-1.2, the area around the nose (19.5%) with mite density of 7.1+/-1.5, then chin (15.6%) with a density of 8.2+/-1.4 and lastly the area around the mouth (14.1%) with a mite density of 14.2+/-1.3. Undoubtedly, infestation with D. folliculorum particularly in large number causes rosacea. PMID- 11775113 TI - Coccidiosis among malnourished children in Mansoura, Dakahlia Governorate, Egypt. AB - Stool samples of 36 malnourished and 36 healthy control children were examined for oocysts of Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli and Microsporidium. C. parvum infection (single and mixed) was detected in 13.9% and 5.6% in malnourished and control children respectively. C. cayetanensis oocysts were detected in 5.6% malnourished children and in 2.8% of control group. I. belli oocysts were detected only in malnourished children 2.8%. On the other hand, no Microsporidium oocysts were detected in both malnourished and control children. PMID- 11775114 TI - Laboratory evaluation of the insecticidal activity of camphor on the development of Oestrus ovis larvae. AB - The essential oil of E. globulus leaves or camphor against the maturation of Oestrus ovis larvae was evaluated at the laboratory conditions. Camphor at concentrations 1:0 and 1.1 showed 100% mortality rate. At concentrations of 1:2 1:6 the mortality rate ranged between 45-98%. On the other hand, 38 or 27.5% of the developed pupae emerged to adults but only 36.8% of them were fertile. Camphor is safely used in Medicine. So, it is recommended in controlling the zoonotic myiasis producer, O. ovis. PMID- 11775115 TI - Evaluation of the effect of a plant alkaloid (berberine derived from Berberis aristata) on Trichomonas vaginalis in vitro. AB - Berberine is a quaternary alkaloid derived from the plant Berberis aristata having antibacterial, antiamoebic, antifungal, antihelminthic, leishmanicidal and tuberculostatic properties. The effect of berberine sulphate salt on the growth of Trichomonas vaginalis in vitro was compared to the efficacy of metronidazole as a reference drug. Results showed that berberine sulphate was comparable to metronidazole as regards potency with the advantage of being more safe and possible replacement in metronidazole resistant cases. PMID- 11775116 TI - Serum levels of some cytokines and soluble adhesion molecules in normal and patients with malignant malaria in Zambia. AB - The present study revealed no changes in the serum levels of IL-8 in malaria patients compared with controls. Such result however, does not exclude a role for IL-8 in falciparum malaria, as it is produced by activated endothelial cells that may be captured by receptors on the endothelial surface. This would allow local concentrations of IL-8 to be generated at the vessel wall without being shed into the circulation. The marked elevation of ICAM-1 and VCAM-1 in serum of falciparum malaria patients may support the concept that dysfunction of the endothelium is important in the pathophysiology of the disease. Increased level of IL-6 in serum of patients may contribute to endothelial damage and dysfunction by expression of endothelial adhesion molecules that in turn result in infected erythrocytes attraction to the endothelium and pathologic endothelial dysfunction. PMID- 11775117 TI - Cellular response to Schistosoma mansoni infection in Biomphalaria alexandrina strains selected for susceptibility and resistance. AB - Exposure of juvenile and adult Biomphalaria alexandrina to Schistosoma mansoni miracidia resulted, typically, in three susceptibility patterns: a) non-infected snails; b) normal infections, and c) retarded infections. Under laboratory conditions, a vigorous resistant-type cellular response to invading miracidia was seen in the histological sections of non-susceptible snails. Accordingly, they were classified as resistant snails. Data pertaining to the influence of host size on suceptibility to S. mansoni indicates that adult snails (i.e. 10-20 mm shell diameter) were significantly less likely to harbour sporocysts than juvenile ones (i.e. 5-10 mm shell diameter). Cellular reaction to the infection varied with sporocysts location and length of infection. At 2 days post-exposure (DPE), most sporocysts were viable. Approximately 8-12% of the sporocysts had elongated shaped transverse constriction and were categorized "normal", while those showing no elongation were categorized "retarded". All remaining sporocysts at 4 DPE were categorized "dead", while at 30 DPE, most sporocysts were "amorphous" with eosinophilic masses. Although encapsulation of sporocysts never occurred in susceptible snails, haemocyte aggregations could sometimes be observed in the proximity of well developed sporocysts. In resistant snails, this cellular response continued to increase and resulted in the encapsulation of the sporocysts. In susceptible snails, the nucleus of secretory cells of the albumen cytoplasm were different in susceptible and resistant snails. PMID- 11775118 TI - Effect of various foods on Biomphalaria alexandrina and Bulinus truncatus and their susceptibility to schistosome miracidia. AB - The tested foods are tropical fish food (tetramine), rat food, blue green algae, dried lettuce leaves and a mixture of all these foods. The results indicated that feeding of B. alexandrina on a mixture of foods increased their growth and survival rates and their susceptibility to S. mansoni. Tetramine elevated the egg laying capacity of snails compared to other tested foods. The hatchability of eggs of B. alexandrina fed on algae for a period of 16 weeks showed the highest rate followed by snails fed on a mixture of foods and then tetramine. B. truncatus maintained on a mixture of foods for 16 weeks, exhibited an increase in their growth, egg-laying, survival rates and recorded the highest infection rate with S. haematobium than other foods. Among the used foods, the hatchability of eggs of B. truncatus fed on tetramine for 16 weeks was the highest one. PMID- 11775119 TI - Six digenetic trematodes infecting the hamour fish (Epinephelus chlorostigma) in the Arabian Gulf, Saudi Arabia. AB - No doubt, parasites infecting fish have a direct or indirect effect on the human welfare. This paper described six species of trematodes infecting Epinephelus chlorostigma (Family: Serranidae). These parasites were Prosorhynuchus epinepheli, P. thapari, Allopodocotyle epinepheli, Helicometrina nimia, Erilepturus hamati and E. lemeriensis. Camera Lucida and photos were given and the results were discussed. PMID- 11775120 TI - Multilocular echinococcosis in humerus: a case report. AB - Hydatid cysts caused by E. multilocularis are less common than those caused by E. granulosus (Pintilie et al., 1996). Infection in the bones is rare, accounts to 0.9-2% of all hydatid cysts (Wirbel et al., 1997). A thirty-five-year old female was presented with a four month history of pain and swelling in her humerus. Plain radiography (Fig. 1) and ultrasonography revealed partial destruction of bone. Laboratory investigations revealed Hb, 15.2 gm, ESR, 11 1st hr and WBC, 10,000. Indirect haemagglutination test using hydatid antigen was positive (1/16,000) and ELISA (IgG) was positive (1/4096). Lung, liver and brain scans were normal. Endosteal-sarcoma was considered and a biopsy was performed. Histopathological examination of bone tissue, showed many cysts (Fig. 11). On surgical operation, a huge number of cysts were found, and removed. The patient was given Albendazole in the recommended dose (Mazyad et al., 1998), and followed up. Six months later, all symptoms and signs regressed. Again three months more, the serological levels markedly decreased and X ray was normal. PMID- 11775121 TI - Water pollution is a risk factor for Cryptosporidium infection in Gharbia Governorate. PMID- 11775122 TI - Abstract, closing summary, and table of contents for Laragh's 25 lessons in pathophysiology and 12 clinical pearls for treating hypertension. AB - These 25 lessons 1) review the roles of plasma renin levels for causing malignant and most essential hypertension and their related vascular injuries (heart attack, heart failure, kidney failure and stroke); 2) review how antihypertensive anti-R drugs that block renin activity (beta blockers, the first converting enzyme inhibitor from venom, and the first angiotensin receptor blocker) were used to reveal plasma renin involvement in the hypertension of medium and high renin patients and to show; 3) that the 30% with low renin essential hypertension do not respond to R drugs, are not prone to heart attack or stroke, and BP is corrected instead by the natriuretic anti-V drugs (diuretics, spironolactone, CCB, alpha blockers); 4) thus, all hypertensives can be divided into R patients who have too much renin vasoconstriction or V patients who instead have predominant sodium-volume mediation. Furthermore, all antihypertensive drug classes can be divided into R drugs that block the renin factor, or V drugs that reduce body sodium volume; 5) these findings document our conception of two biochemically and physiologically different final factors that sustain all BP in which the sodium-volume factor continuously sustains cardiac output and flow while plasma renin-angiotensin sets total peripheral resistance (TPR), which, within the Poiseuille Equation (BP = cardiac output [CO] x TPR) describes our [Na+-volume x renin-angiotensin vasoconstriction] model that supports all normotension or hypertension; 6) in this light, we designed a visit-by-visit method for treating untreated hypertensives using the ambient plasma renin level and BP responses to guide primary drug therapy against either the V or R factor; and 7) for also correcting nonresponders receiving multiple drugs where renin testing correctly guides addition or subtraction of drugs depending on whether the test indicates unresponsiveness due to a reactive sodium-volume excess, or to lack of effectiveness of an R drug in a V patient or of a V drug in an R patient, or from large reactive increases in renin that override the R drug, calling for strengthening the R and/or removing V drugs. This objective, biochemically based method results in effective longterm BP control of nearly all patients using fewer, but the correct drug(s) for each individual. PMID- 11775123 TI - Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives. AB - BACKGROUND: Individuals differ in their blood pressure (BP) response to changes in dietary sodium (Na+) intake. It is possible that differences in BP responses to dietary Na+ are influenced by genes. METHODS: A total of 35 older (62.9 +/- 1.2 years) hypertensive subjects had their mean arterial blood pressure (MABP) determined after 8 days of low (20 mmol/day) and high (200 mmol/day) Na+ intake. The insertion/ deletion polymorphism of the angiotensin converting enzyme (ACE) gene was genotyped with standard polymerase chain reaction methods. RESULTS: Of the 35 subjects, 24 were classified as sodium-sensitive (> or = 5 mm Hg increase in MABP in response to the increase in dietary Na+) and 11 were classified as sodium-resistant (<5 mm Hg increase in MABP). Those homozygous for the insertion allele of the ACE gene (insertion/insertion [II]; n = 8) had lower (P = .04) MABP responses to the increase in dietary Na+ (0 +/- 3 mm Hg) compared to heterozygotes (insertion/deletion [ID]; n = 20) (9 +/- 2 mm Hg; P = .0001) and those homozygous for the deletion allele (deletion/deletion [DD]; n = 7) (9 +/- 3 mm Hg; P = .05). The prevalence of sodium sensitivity was higher (P = .0083) in DD (71%) and ID (83%) compared to II (25%) genotype groups. CONCLUSIONS: Based on these data in older hypertensive individuals, we conclude that the ACE gene ID and DD genotypes are associated with an increase in BP during a high Na+ diet, which is consistent with the phenotypic characteristic of sodium sensitivity. PMID- 11775124 TI - Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia. AB - BACKGROUND: In a genome scan for familial combined hyperlipidemia (FCHL), a locus contributing to systolic blood pressure (SBP) has been identified on chromosome 4, containing the a-adducin gene (ADD1). In previous studies, an association has been found between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. In this study, we investigated the association between the a adducin Gly460Trp polymorphism and blood pressure in FCHL patients. METHODS: A total of 79 unrelated patients with FCHL and 121 unrelated controls (spouses) were recruited for the study. Blood pressure was measured in a standardized fashion, with the subject in sitting position after 10 min of rest. The alpha adducin Gly460Trp polymorphism was detected by mutagenically separated polymerase chain reaction. RESULTS: The genotype frequencies of both FCHL patients and controls were in Hardy-Weinberg equilibrium. The alpha-adducin Gly460Trp polymorphism showed a significant association with FCHL, the number of subjects carrying a 460Trp allele was significantly higher in patients compared with controls (53% v 33%, chi2 = 8.0, P = .018). In FCHL patients carrying at least one 460Trp allele, SBP was significantly higher compared with patients homozygous for the 460Gly allele (140 mm Hg and 130 mm Hg respectively, P = .015). CONCLUSIONS: This study shows that the 460Trp allele is associated with FCHL. Furthermore, SBP is increased in patients carrying the 460Trp allele. PMID- 11775125 TI - G protein beta3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension. AB - BACKGROUND: A nucleotide substitution (C-->T) at position 825 of the gene GNB3 encoding the beta3 subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives. PROCEDURES: Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. RESULTS: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 +/- 1.5 v 89.7 +/- 1.5 g/m2; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity. CONCLUSIONS: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies. PMID- 11775126 TI - The glycine allele of a glycine/arginine polymorphism in the beta2-adrenergic receptor gene is associated with essential hypertension in a population of Chinese origin. AB - BACKGROUND: Several studies implicate polymorphisms in the human beta-adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 (Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95% CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population. There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2-adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin. PMID- 11775127 TI - Association of beta2-adrenoceptor Gln27Glu variant with body weight but not hypertension. AB - Beta2-adrenoceptor (beta2-ADR)-mediated vasodilatation decreases vascular reactivity and blood pressure (BP) and chromosome 5 where its gene (ADRB2R) resides and shows linkage to hypertension (HT). A Gln27Glu ADRB2R variant confers resistance to agonist-induced desensitization and enhanced vasodilator response to isoprenaline. Therefore, we carried out a case-control study in a cohort of HT and normotensive (NT) Anglo-Celtic Australian white subjects whose parents had a similar BP status as the subjects. Glu27 frequency was 0.41 in 108 HT and 0.42 in 141 NT (chi2 = 0.05, P = .82). Within the HT group, the Glu27 allele was more prevalent in 61 subjects who were overweight (body mass index [BMI] > or = 25 kg/m2) compared with 41 who were lean (BMI <25 kg/m2); ie, 0.49 v 0.31, respectively (chi2 = 6.4, P = .012). Furthermore, Glu27 tracked with elevation in BMI in these subjects: 24 +/- 4 kg/m2, 27 +/- 5 kg/m2, and 28 +/- 5 kg/m2 for Gln/Gln, Gln/Glu, and Glu/Glu, respectively (P = .0058 by one-way ANOVA). Thus, the Gln27Glu beta2-ADR variant is excluded in HT, but might influence body weight. PMID- 11775128 TI - Maximal exercise capacity is related to cardiovascular structure in patients with longstanding hypertension. A LIFE substudy. Losartan Intervention For Endpoint Reduction in Hypertension. AB - BACKGROUND: Cardiovascular hypertrophy and remodeling in patients with never treated hypertension has been associated with impaired exercise capacity, but whether this relationship remains in patients with longstanding hypertension and target organ damage is less elucidated. METHODS: In 43 unmedicated patients with essential hypertension and electrocardiographic left ventricular (LV) hypertrophy, we measured maximal workload and oxygen reserve by bicycle test, 24 h ambulatory blood pressure (BP), LV mass index by magnetic resonance imaging (LVMI(MRI), n = 31), LVMI(echo) and systemic vascular compliance by echocardiography, minimal forearm vascular resistance (MFVR) by plethysmography, and intima media thickness and distensibility in the common carotid arteries by ultrasound. RESULTS: The patients did not achieve the maximal workload as predicted by age, gender and body composition (146[129-163] v 162[146-179] Watt, P = .01). This impaired exercise capacity, calculated as the ratio between achieved and predicted maximal workload, was in simple regression analyses related to lower distensibility of the common carotid artery (r = 0.38, P = .01) and lower oxygen reserve (r = 0.68, P < .001). In multiple regression analyses, lower oxygen reserve was related to higher LVMI(MRI) (beta = -0.44), lower systemic vascular compliance (beta = -0.36), and higher MFVR (beta = -0.52) (adjusted R2 = 0.53, P < .001). CONCLUSIONS: Patients with longstanding hypertension and target organ damage cannot achieve the predicted maximal workload. This impaired exercise capacity was associated with lower common carotid distensibility and lower oxygen reserve. The latter was independently related to LV hypertrophy, low systemic vascular compliance and peripheral vascular remodeling, suggesting that cardiovascular hypertrophy and remodeling may reduce exercise capacity by itself. PMID- 11775129 TI - Atrophy or hypertrophy in chronic renal ischemia: role of the IGF-I system. AB - To examine the role of insulin-like growth factor-1 (IGF-1) in renal atrophy of rats with two-kidney, one-clip (2K1C), in which the clipped kidney atrophies, and in the one-kidney, one-clip (IK1C) model of renovascular hypertension, in which it hypertrophies, we studied levels of IGF-I, mRNA, and protein in 2K1C, IK1C, and unilateral nephrectomy (NPX) in rats by solution-hybridization RNase protection, and radioimmunoassay, respectively, both cross-reactively and longitudinally at 3, 10, and 30 days after clipping. Three days after clipping, there were no differences in blood pressure or kidney size; however, 10 and 30 days postoperation, the clipped kidney shrank in the 2K1C model. The nonclipped 2K1C and the clipped lK1C and unilateral nephrectomy kidneys increased in weight (P < .05. At day 3 the IGF-I levels were lower (557 +/- 54, 335 +/- 61 ng/g in control and clipped 2K1C, P < .05, v 1,074 +/- 186, 1,109 +/- 54, and 1,154 +/- 200 ng/g kidney, nonclipped 2K1C, 1K1C, and NPX, respectively). At 30 days the IGF-I levels were 300 +/- 24 ng/g in control (P < .05) v clipped 2K1C, 160 +/- 19, 218 +/- 20 ng/g in nonclipped 2K1C and 406 +/- 33 and 470 +/- 34 ng/g in 1K1C and NPX, respectively (P < .05) v control and clipped 2K1C. Kidney mRNA was increased in the clipped 2K1C. In conclusion, the kidney that had higher IGF-I levels early in nonclipped 2K1C, 1K1C, and nephrectomy hypertrophied, and the kidney (clipped 2K1C) that failed to increase IGF-I atrophied. IGF-I levels are dissociated from the local mRNA message. PMID- 11775130 TI - Blood pressure and angiotensin converting enzyme inhibitor use in hypertensive patients with chronic renal insufficiency. AB - BACKGROUND: Hypertension treatment is important in managing chronic renal insufficiency (CRI). Little is known, however, about the blood pressure (BP) control achieved or the pattern of antihypertensive drug prescription among CRI patients. METHODS: Using computerized medical records, we studied 3,089 adult hypertensive subjects treated at Brigham and Women's Hospital (Boston, MA) from 1990 through 1998. All subjects had at least two serum creatinine measurements 2 years apart, at least two BP readings, and online weight (to estimate Cockcroft Gault creatinine clearance [CrCl]). RESULTS: The average mean arterial pressure over time (mean MAP) was 103 +/- 9 mm Hg among those with CrCI >60 mL/min, 102 t 9 mm Hg among those with CrCl 41 to 60 mL/min. and 101 +/- 9 mm Hg among those with CrCl 21 to 40 mL/min. There were no significant differences in mean MAP among the different categories of renal function in the multivariate analysis (P = .26 for trend). The proportion of patients with final systolic BP < 160 mm Hg and diastolic BP <90 mm Hg was 68% and did not vary with renal function (P = .68 for trend). The proportion of subjects who were prescribed ACE inhibitors was 38% among those with CrCl >60 mL/min, 36% among those with CrCI 41 to 60 mL/min, and only 27% among those with CrCl 21 to 40 mL/min (P = .003 for trend). CONCLUSIONS: The BP control achieved among hypertensive CRI subjects, although no worse than that among those without CRI, was found to be suboptimal. Patients with CrCl 21 to 40 mL/min were less likely to be prescribed ACE inhibitors than were those with CrCl >60 mL/min. Improvement is needed in the clinical management of these factors that can influence the progression of CRI. PMID- 11775131 TI - Sibling correlation of left ventricular mass and geometry in hypertensive African Americans and whites: the HyperGEN study. Hypertension Genetic Epidemiology Network. AB - BACKGROUND: Evidence suggests that left ventricular (LV) mass is under genetic control, independently of risk factors known to influence LV size and geometry. METHODS: As part of the HyperGEN study, four field centers recruited African American and white hypertensive siblings (n = 1,664), aged 23 to 87 years. Two dimensionally guided M-mode echocardiography was performed, and LV mass and relative wall thickness (RWT) were measured at a central reading center. Familial correlations were calculated separately for each ethnic group using maximum likelihood methods, adjusted for the potential confounding influences of age, gender, systolic blood pressure, and obesity. RESULTS: In African Americans, brother-sister, brother-brother, and sister-sister correlation coefficients and standard errors for LV mass were 0.29 (0.08), 0.44 (0.10), and 0.33 (0.05). In whites, the corresponding correlations were lower than in African Americans at 0.05 (0.08), 0.12 (0.11), and 0.22 (0.09), respectively. Sibling correlation of LV geometry, assessed by RWT, was less in African Americans than in whites: brother-sister, 0.04 (0.10) v 0.21 (0.10), brother-brother, 0.12 (0.22) v 0.28 (0.09), and sister-sister, 0.11 (0.07) v 0.19 (0.11). CONCLUSIONS: LV mass is strongly correlated in hypertensive African American siblings, and modestly correlated in their white counterparts, whereas RWT has stronger sibling correlation in whites. The patterns of familial correlation of echocardiographic LV mass and RWT suggest that the genetic underpinnings of LV hypertrophy and geometric remodeling may differ among ethnic groups. PMID- 11775132 TI - Left ventricular mechanical efficiency in hypertensive patients with and without increased myocardial mass and with normal pump function. AB - Left ventricular hypertrophy (LVH) is a physiologic process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular contractile performance, mechanical efficiency and ventriculoarterial coupling are preserved in hypertensive patients with LVH. To assess the differences between patients with and without LVH, left ventricular contractile performance and the ventriculoarterial coupling were compared in two groups of hypertensive patients with similar body surface area and arterial pressures, and normal pump function: 30 patients with LVH (group 1) and 23 without LVH (group 2). Left ventricular angiography coupled with simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and pressure-volume area (PVA). Myocardial contractile performance, assessed by Ees normalized by myocardial mass and by ESSVR, was lower in group I than in group 2 (1.23 +/- 0.28 v 1.89 +/- 0.48 mm Hg/mL/100 g, and 3.85 +/- 0.99 v 5.13 +/- 0.56 g/cm2/mL, respectively, both P < .001). Ventriculoarterial coupling evaluated through Ea/Ees ratio, and mechanical efficiency evaluated through EW/PVA ratio, were similar in the two groups (0.53 +/- 0.08 v 0.51 +/- 0.05, and 0.78 +/- 0.03 v 0.80 +/- 0.02, respectively, NS). In conclusion, this study shows that ventriculoarterial coupling and mechanical efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in hypertensive patients, the matching between left ventricular performance and arterial load and the energy transfer are preserved either through left ventricular hypertrophy with moderate depression of myocardial contractile performance or through enhancement of myocardial contractile performance in patients with normal left ventricular mass. PMID- 11775133 TI - Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy. AB - BACKGROUND: The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. METHODS: Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER verapamil in patients with mid-stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil (N = 273) or placebo (N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. RESULTS: Treatment with COER-verapamil caused significant reductions in 24-h and early morning systolic and diastolic BP in all of the subpopulations as compared with placebo (P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (-15.1 v -10.0 mm Hg; P < .001) and diastolic (-10.4 v -8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (-10.2 v -8.2 mm Hg; P < .05) and heart rate (-5.7 v -4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. CONCLUSIONS: Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients. PMID- 11775134 TI - Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension. AB - BACKGROUND: Eprosartan is a new nonphenyl angiotensin II receptor blocker, which has been approved for the treatment of hypertension. Although the drug has a relatively short plasma half-life of 5 to 9 h, clinical studies have suggested that its antihypertensive effect persists for 24 h. METHODS: We assessed both the changes in 24-h and trough blood pressure (BP) (last 4 h of the ambulatory BP while the patient was awake) of eprosartan at doses of 600 and 1,200 mg once daily in a randomized, double-blind, placebo-controlled trial. Ambulatory BP was monitored at placebo baseline and after 8 weeks of double-blind therapy. RESULTS: Two hundred patients randomized in the study with 177 patients completing the trial. The 24-h change in BP from baseline was 0.2/0.1 +/- 1.4/1.0 mm Hg, -7.9/ 5.4 +/- 1.0 mm Hg (P < .0001), and -7.4/-5.0 +/- 0.9 mm Hg (P < .0001) in the placebo, 600-mg eprosartan, and 1,200-mg eprosartan groups, respectively. Changes in trough ambulatory BP showed significant reductions of -6.3/-4.1 +/- 1.6/1.1 mm Hg and -7.7/-5.5 +/- 1.5/1.0 mm Hg for 600 mg of eprosartan and 1,200 mg of eprosartan, respectively. CONCLUSIONS: These data demonstrate that eprosartan at doses of 600 or 1200 mg significantly reduced BP throughout an entire 24-h dosing period. There were no differences between the 600- and 1,200-mg dose; thus, 600 mg once daily should be the only dose used in the treatment of hypertension with eprosartan. PMID- 11775136 TI - Is resistant hypertension really resistant? AB - BACKGROUND: Managing resistant hypertension is difficult and mostly involves expensive testing seeking an underlying secondary cause. This study was undertaken to determine 1) the extent of the white-coat phenomenon in patients with resistant hypertension, and 2) whether 24-h ambulatory blood pressure (BP) monitoring (ABPM) or having BP recorded by a nurse instead of the referring doctor could clarify how many apparently resistant hypertensives actually have controlled BP. METHODS: This study involved 611 patients with BP > or = 140/90 mm Hg who were referred for 24-h ABPM by their specialist or general practitioner, including 277 patients who were taking no antihypertensives (group 1), 216 taking one or two antihypertensive drugs (group 2), and 118 taking at least three antihypertensives in combination (group 3). Each had BP recorded by one of two nurses before 24-h ABPM. Controlled BP was defined as awake ambulatory BP <135/85 mm Hg and the white-coat effect was the difference between the BP recorded by the referring doctor or nurse and the average awake ambulatory BP. RESULTS: Those with resistant hypertension (group 3) were older (61 years (12) v group 1: 46 years (14) and group 2: 56 (14) years; P < .001), but were of similar weight, height, and arm circumference to the other groups. Referral systolic, but not diastolic BP was higher in resistant hypertensives (mean 171/95 v 154/95 mm Hg and 164/94 mm Hg, respectively, P < .001 for systolic BP only). Twenty-eight percent of resistant hypertensives and 32% of those taking no antihypertensive drugs had normal awake ambulatory BP and the white-coat effect attributable to the referring doctor was always greater than that due to the nurse (range 16 to 26/12 to 14 mm Hg v 9 to 17/4 mm Hg, P < .001). Nurse recorded BP was highly sensitive (97%) in identifying awake hypertension but lacked specificity (57%) to replace ABPM. CONCLUSION: Our results show that approximately one in four patients with apparent resistant hypertension referred for ABPM have controlled BP and one-third of patients referred for initial evaluation of office or clinic hypertension have normal BP using ABPM, ie, white-coat hypertension. Twenty-four hour ABPM appears an appropriate initial step before further investigating or treating patients with apparently resistant hypertension. PMID- 11775135 TI - Effects of phytoestrogens on DNA synthesis and creatine kinase activity in vascular cells. AB - BACKGROUND: The aim of this study was to assess the effect of phytoestrogens on the human vascular wall in vitro. METHODS: We compared the effects of E2 to those of genistein (G), daidzein (D), biochanin A (BA), equol (EQ), and quecertin (Qu) on 3[H] thymidine incorporation and creatine phosphokinase (CK) activity in human vascular smooth muscle cells (VSMC) and in a human endothelial cell line (E304). RESULTS: In VSMC, E2, the estrogen antagonist raloxifene (RAL), G, and D stimulated DNA synthesis at low concentrations and suppressed 3[H] thymidine incorporation at higher concentrations. In contrast, BA and EQ had a monophasic stimulatory effect on 3[H] thymidine incorporation (87% +/- 9% and 54% +/- 17%, respectively) whereas Qu had only an inhibitory effect (-36 +/- 16% at 30 nmol/L). In E304 cells, all phytoestrogens stimulated DNA synthesis in a dose related manner. In both cell types E2, RAL as well as all phytoestrogens increased CK-specific activity. The administration of phytoestrogens to immature female rats resulted in increased CK in the aorta (Ao) (60% to 220%) and in the left ventricle of the heart (Lv) (45% to 160%). Similar increases in Ao and Lv CK were also induced by E2 and all five phytoestrogens in ovariectomized (OVX) female rats. RAL antagonized phytoestrogen-induced CK activity in human vascular cells and in the rat Ao and Lv tissue but did not block phytoestrogen effects on DNA synthesis in human VSMC. CONCLUSIONS: Although phytoestrogens have estrogen mimetic effects on cell growth and CK in cultured human vascular cells and on CK in rat vascular tissues in vivo, the effects on human VSMC replication are highly dependent on the concentration and the particular phytoestrogen under investigation. PMID- 11775137 TI - Renin system activation and delayed function of the renal transplant. AB - Delayed graft function (DGF), defined as persistent renal failure that requires dialysis within the first week after kidney transplantation, occurs commonly after cadaveric renal transplantation (CRT). This has important implications for long-term outcome because the 1-year allograft survival rate is significantly reduced when DGF occurs. The mechanisms contributing to the development of DGF are not well established. However, several lines of evidence indicate that excess renin system activity, in both the cadaver kidney donor and recipient, contributes importantly to the pathogenesis of DGF. If this hypothesis can be verified in clinical studies, then pharmacologic agents that interrupt the renin angiotensin system (eg, type 1 angiotensin II receptor blockade, angiotensin converting enzyme inhibition, and beta-adrenergic blockade) in the donor and recipient might significantly improve the outcome of cadaveric renal transplants. PMID- 11775138 TI - Effect of testosterone on intracellular Ca++ in vascular smooth muscle cells. PMID- 11775139 TI - New frontiers in aldosterone/mineralocorticoid biology: a reemerging force in target organ damage and hypertension. PMID- 11775140 TI - New onset severe hypertension in an asymptomatic 6-year-old girl. PMID- 11775141 TI - Removal of endocrine-disrupting chemicals in activated sludge treatment works. AB - The release of endocrine-disrupting chemicals into the aquatic environment has raised the awareness of the central role played by sewage treatment in lowland water quality. This review focuses on the activated sludge process, which is commonly used to treat sewage in large towns and cities and which successfully removes the bulk of the organic compounds that enter the works. However, not all compounds are completely broken down or converted to biomass. For example, the estrogenic alkylphenols and steroid estrogens found in effluent are the breakdown products of incomplete breakdown of their respective parent compounds. Batch microcosm studies have indicated that estrone, ethinylestradiol, and alkylphenols will not be completely eliminated in activated sludge over typical treatment times. Field data suggest that the activated sludge treatment process can consistently remove over 85% of estradiol, estriol, and ethinylestradiol. The removal performance for estrone appears to be less and is more variable. Because of its relatively high hydrophobicity, the accumulation of alkylphenol in sludge has been observed. Although it has not been examined, accumulation of ethinylestradiol in sludge is a possibility due to its recalcitrance and hydrophobicity. A comparison between the concentrations of some of the major endocrine-active chemicals in effluents and their biological potencies has been made, to direct attention to the chemicals of most concern. While water purification techniques such as UV or activated charcoal could significantly remove these microorganic contaminants, the high costs involved suggest that research into the potential for treatment optimization should receive more attention. PMID- 11775142 TI - Estimate of mercury emissions to the atmosphere from petroleum. AB - An estimate of the contribution of mercury to the atmospheric environment from petroleum processed in the United States is constructed from recent data. The estimate is based on a mass balance approach for mercury in crude oil, in refined products, and in waste streams (air, water, solid waste) from refineries. Although there are insufficient data at present to have a high degree of confidence in the mean amount and range of mercury concentrations in crude oil or in refined products, the framework of the estimate should assist direction for the acquisition of additional data. On the basis of selected data that put the estimated mean concentration of total mercury in crude oil close to 10 ppb, it is calculated that the total amount of mercury in U.S. petroleum processed yearly is slightly over 8000 kg/yr. Of this amount, approximately 6000 kg/yr is estimated to be emitted to the atmosphere from combustion of liquid hydrocarbon fuels, which represents about 10% of the U.S. yearly emission rate of atmospheric mercury from coal combustion. The material balance predicts that the amount of mercury in air emissions from all U.S. refineries is on the order of 1500 kg/yr based on the assumption that fugitive mercury emissions from refineries are negligible. Atmospheric emissions of mercury from fuel oil burned in the United States are estimated in the U.S. EPA Mercury Report to Congress to be approximately 10000 kg/yr, and this estimate may be in error on the high side by a factor of 3-10. If the mean amounts of mercury in U.S. distillate and residual fuel oils are in the range of 5-15 ppb, as suggested by more recent data, then U.S. fuel oil combustion should contribute no more that about 1000-3000 kg/yr (emission ratio = 1) of mercury to the atmospheric burden. PMID- 11775143 TI - Identifying sources of stress to native aquatic fauna using a watershed ecological risk assessment framework. AB - The free-flowing Clinch and Powell River Basin, located in southwestern Virginia, United States, historically had one of the richest assemblages of native fish and freshwater mussels in the world. Nearly half of the species once residing here are now extinct, threatened, or endangered. The United States Environmental Protection Agency's framework for conducting an ecological risk assessment was used to structure a watershed-scale analysis of human land use, in-stream habitat quality, and their relationship to native fish and mussel populations in order to develop future management strategies and prioritize areas in need of enhanced protection. Our analyses indicate that agricultural and urban land uses as well as proximity to mining activities and transportation corridors are inversely related to fish index of biotic integrity (IBI) and mussel species diversity. Forward stepwise multiple regression analyses indicated that coal mining had the most impact on fish IBI followed by percent cropland and urban area in the riparian corridor (R2 = 0.55, p = 0.02); however, these analyses suggest that other site-specific factors are important. Habitat quality measures accounted for as much as approximately half of the variability in fish IBI values if the analysis was limited to sites within a relatively narrow elevation range. These results, in addition to other data collected in this watershed, suggest that nonhabitat-related stressors (e.g., accidental chemical spills) also have significant effects on biota in this basin. The number of co-occurring human land uses was inversely related to fish IBI (r = -0.49, p < 0.01). Sites with > or = 2 co-occurring land uses had >90% probability of having <2 mussel species present. Our findings predict that many mussel concentration sites are vulnerable to future extirpation. In addition, our results suggest that protection and enhancement of naturally vegetated riparian corridors, better controls of mine effluents and urban runoff, and increased safeguards against accidental chemical spills, as well as reintroduction or augmentation of threatened and endangered species, may help sustain native fish and mussel populations in this watershed. PMID- 11775145 TI - Biohydrogen production as a function of pH and substrate concentration. AB - The conversion of organics in wastewaters into hydrogen gas could serve the dual role of renewable energy production and waste reduction. The chemical energy in a sucrose rich synthetic wastewater was recovered as hydrogen gas in this study. Using fractional factorial design batch experiments, the effect of varying pH (4.5-7.5) and substrate concentration (1.5-44.8 g COD/L) and their interaction on hydrogen gas production were tested. Mixed bacterial cultures obtained from a compost pile, a potato field, and a soybean field were heated to inhibit hydrogen consuming methanogens and to enrich sporeforming, hydrogen-producing acidogens. It was determined that the highest rate (74.7 mL H2/(L*h)) of hydrogen production occurred at a pH of 5.5 and a substrate concentration of 7.5 g COD/Lwith a conversion efficiency of 38.9 mL H2/(g COD/L). The highest conversion efficiency was 46.6 mL H2/(g COD/L). PMID- 11775144 TI - Processes of nickel and cobalt uptake by a manganese oxide forming sediment in Pinal Creek, Globe mining district, Arizona. AB - A series of column experiments was conducted using manganese oxide coated sediments collected from the hyporheic zone in Pinal Creek (AZ), a metal contaminated stream, to study the uptake and retention of Mn, Ni, and Co. Experimental variables included the absence (abiotic) and presence (biotic) of active Mn-oxidizing bacteria, the absence and presence of dissolved Mn, and sediment manganese oxide content. Uptake of Mn under biotic conditions was between 8 and 39% higher than under abiotic conditions. Continuous uptake of Mn due to biotic oxidation was evident from extraction of column sediments. Manganese uptake is hypothesized to initially occur as adsorption, which led to subsequent surface and/or microbial oxidation. Complete breakthrough of Ni within 100 pore volumes indicated no process of continuous uptake and was modeled as an equilibrium adsorption process. Nickel uptake in the presence of dissolved Mn was 67-100% reversible. Sediment extractions suggest that Ni uptake occurred through weak and strong adsorption. Continuous uptake of cobalt increased with sediment manganese oxide content, and Co uptake was up to 75% greater under biotic than abiotic conditions. Cobalt uptake was controlled by both existing and newly formed manganese oxides. Only a small amount of Co uptake was reversible (10 25%). XANES spectral analysis indicated that most Co(II) was oxidized to Co(III) and probably incorporated structurally into manganese oxides. Although manganese oxides were the primary phase controlling uptake and retention of Mn, Ni, and Co, the mechanisms varied among the metals. PMID- 11775146 TI - Ammonia exchange between the atmosphere and the surface waters at two locations in the Chesapeake Bay. AB - Excess phytoplankton production, which contributes to hypoxic conditions, is nitrogen limited in the Chesapeake Bay during the summer months. Therefore, understanding the flux of ammonia by direct deposition to the biologically active surface layer is critical to understanding the nutrient dynamics of the bay. This paper presents the results of a 2-yr study measuring gaseous ammonia (NH3) and aerosol ammonium (NH4+) in Baltimore and Solomons, MD, from which direct atmospheric loading of total ammonia (Nt = NH3 + NH4+) to the Chesapeake Bay is estimated. Mean atmospheric concentrations of total ammonia for Baltimore and Solomons were 2.7 +/- 1.7 and 1.0 +/- 0.8 microg of N m(-3), respectively. Monte Carlo estimates of gross dry deposition ranged from <100 to 4900 microg of N m( 2) d(-1). However, based upon water quality parameters, Monte Carlo estimates of gross volatilization of NH3 were calculated to range from <100 to 7700 microg of N m(-2) d(-1). The resulting net air-sea exchange flux varied seasonally from a net deposition into the water during the winter to a net volatilizing into the atmosphere during the summer. A total of 60% of the paired air-water samples had flux estimates that were not significantly different than equilibrium at the 90% confidence interval. The gross deposition, gross volatilization, and net air-sea fluxes were greater and more variable in Baltimore relative to the rural site. Atmospheric ammonia concentrations decrease during the winter at the rural site. However, the net exchange is still into the water due to an exponential decrease in [NH3]eq with temperature. These results indicate that the nitrogen-limited Chesapeake Bay can act as a source of ammonia to the local atmosphere. PMID- 11775147 TI - Concentrations and fluxes of hexachlorocyclohexanes and chiral composition of alpha-HCH in environmental samples from the southern Baltic Sea. AB - In summer 1997 and winter 1998, paired boundary air and surface water samples were collected during cruises in the southern Baltic Sea. Simultaneously, deposition samples were taken at Gotland Island, located close to the air-water sampling area. Water samples taken shortly after the flooding of Oder and Wisla Rivers in summer 1997 were also included in the study. Concentrations and gas exchange fluxes of alpha- and gamma-HCH and chiral composition of alpha-HCH were determined. According to fugacity calculations, the HCHs were close to air-sea partitioning equilibrium. The net fluxes varied over time, particularly during summer. Importance of the air to sea removal routes "gross gas deposition" and "wet deposition" were about equal for gamma-HCH, while the scavenging via precipitation was less important for alpha-HCH. Enantiomer fractions were used to estimate the fraction of alpha-HCH in the boundary air layer that had volatilized from the water. During summer, the fraction was approximately 60%, and wintertime significantly less (0-35%). Variations in air mass origin were clearly reflected in net air-sea gas exchange and isomeric and enantiomeric "signatures" in boundary air. The composition of boundary air and precipitation was also variable depending on season. PMID- 11775148 TI - Metabolism of PCBs by the deepwater sculpin (Myoxocephalus thompsoni). AB - Methylsulfonyl-PCBs (MeSO2-PCBs) are hydrophobic organic contaminants that bioaccumulate in the environment similar to their parent molecules, PCBs. Previously, MeSO2-PCBs have primarily been identified in tissues of birds, humans, and other mammals. However, evidence now supports formation of these metabolites in deepwater sculpin, Myoxocephalus thompsoni, a benthic forage fish predominant in the Great Lakes. The ability of deepwater sculpin to form MeSO2 PCBs is unprecedented for a freshwater fish species and presents a novel biochemical pathway for organochlorine metabolism. Additionally, this appears to be a unique PCB metabolic pathway resulting in a reduction of as much as 10% in the sculpin PCB burden, which is further transformed into another class of organic contaminants in the Great Lakes ecosystem. PMID- 11775149 TI - Competitive adsorption of phosphate and arsenate on goethite. AB - The competitive adsorption of phosphate and arsenate on goethite was investigated to better understand the bonding mechanisms for the two ions. The anions were added both simultaneously and sequentially. When added simultaneously, the two ions were adsorbed about equally, with the total surface coverage being slightly greater than for either ion alone. When added sequentially, the extent of exchange for the first ion depended on the equilibration time before the second ion was introduced--the longer the equilibration time the greater the exchange. There is a nonexchangeable fraction for both ions that is approximately equal to the initially adsorbed amount of each ion. The results suggest a two-phase reaction on the surface, with the first phase being a rapid surface complex formation on the goethite surface, followed by the slower buildup of a surface precipitate on the adsorbed layer. The exchangeable ions are in the surface precipitate. These results are incompatible with a surface complexation model (SCM) for anion adsorption on geothite and indicate that the actual reactions are more complicated than the reaction assumed in a SCM. PMID- 11775150 TI - Atmospheric secondary aerosol formation by heterogeneous reactions of aldehydes in the presence of a sulfuric acid aerosol catalyst. AB - Particle growth by the heterogeneous reaction of aldehydes was evaluated in 0.5 m3 Teflon film bags under darkness in the presence of background seed aerosols. The aldehydes used were as follows: glyoxal, butanal, hexanal, octanal, and decanal. To study acid catalyst effects on aldehyde heterogeneous reactions, one of the Teflon bags was initially filled with seed aerosols composed of ammonium sulfate-aerosol acidified with sulfuric acid. These results were compared to particle growth reactions that contained only ammonium sulfate as a background seed aerosol. The gas-phase aldehydes were then added to the Teflon bags. In selected experiments, 1-decanol was also added to the Teflon bags with aldehydes to clarify particle growth via a heterogeneous hemiacetal/acetal formation in the presence/absence of an acid catalyst. The particle size distribution and growth were measured using a scanning mobility particle sizer (TSI-SMPS), and the results were applied to predicting aerosol growth and size distribution changes by condensation and heterogeneous reactions. Aerosols created from the heterogeneous reactions of aldehydes were collected directly on an ungreased zinc selenide (ZnSe) FTIR disk (25 mm in diameter) by impaction. The ZnSe disks were directly analyzed for product functional groups inthe aerosol phase using a Fourier transform infrared (FTIR) spectrometer with a deuterated triglycine sulfate (DTGS) detector. Aerosol growth by heterogeneous aldehyde reactions proceeds via a hydration, polymerization process, and hemiacetal/acetal formation from the reaction of aldehydes with alcohols. These aldehyde heterogeneous reactions were accelerated in the presence of an acid catalyst, H2SO4, and led to higher aerosol yields than when H2SO4 was not present in the seed aerosol. The FTIR spectra obtained from the growing aerosol, also illustrated aldehyde group transformation in the particle phase as a function of the heterogeneous reaction. It was concluded that aldehydes, which can be produced by atmospheric photochemical reactions, can significantly contribute on secondary aerosol formation through heterogeneous reactions in the presence of an acid catalyst. PMID- 11775151 TI - Spectroscopic study of nitroaromatic-smectite sorption mechanisms. AB - Sorption mechanisms of 1,3- and 1,4-dinitrobenzene, 1,3,5-trinitrobenzene (TNB), dinitro-o-creasol, and 6-sec-butyl-2,4-dinitrophenol (DINOSEB) on smectite were investigated using FTIR spectroscopy and HPLC methods. A quantitative method was developed that established a direct link between the HPLC and the FTIR data. Freundlich sorption values ranged from 47 (L g(-1)) for 1,3,5-TNB to 3.7 for DINOSEB and showed that the extent of nitroaromatic compounds (NAC) sorption was strongly dependent on the number and position of the nitro substituents as well as other substituents and steric effects. The amount of 1,3,5-TNB sorbed to smectite was strongly influenced by the nature of the exchangeable cation. Furthermore, the exchangeable cation significantly influenced the positions and relative intensities of the vibrational modes of the -NO2 groups. The strongest perturbations were observed for cations with lower enthalpies of hydration (e.g., K+) and included a red shift of the v(asym)(NO) band, a concomitant blue shift of the v(sym)(NO) band. These changes were accompanied by a 2-fold increase in the relative intensity of the v(asym)(NO) band relative to the intensity of the v(sym) (NO) band. Molecular quantum mechanics calculations were used to rationalize frequency shifts in terms of nitroaromatic interactions with interlayer cations. Results indicate that the sorption of NACs to smectite surfaces is controlled largely by the hydration characteristics of the exchangeable cation, which regulates both cation-nitroaromatic complexation and swelling of the smectite. PMID- 11775152 TI - Partitioning of total mercury and methylmercury to the colloidal phase in freshwaters. AB - Using tangential flow ultrafiltration, total mercury (HgT) and methylmercury (MeHg) concentrations in the colloidal phase (0.4 microm-10 kDa) were determined for 15 freshwaters located in the upper Midwest (Minnesota, Michigan, and Wisconsin) and the Southern United States (Georgia and Florida). Unfiltered concentrations were typical of those reported for freshwater and ranged from 0.9 to 27.1 ng L(-1) HgT and from 0.08 to 0.86 ng L(-1) MeHg. For some rivers, HgT and MeHg in the colloidal phase comprised up to 72% of the respective unfiltered concentration. On average, however, HgT and MeHg concentrations were evenly distributed between the particulate (>0.4 microm), colloidal, and dissolved (<10 kDa) phases. The pool of Hg in the colloidal phase decreased with increasing specific conductance. Results from experiments on freshwaters with artificially elevated specific conductance suggest that HgT and MeHg may partition to different subfractions of colloidal material. The colloidal-phase HgT correlation with filtered organic carbon (OC(F)) was generally poor (r2 < 0.14; p > 0.07), but the regression of MeHg with OC(F) was strong, especially in the upper Midwest (r2 = 0.78; p < 0.01). On a mass basis, colloidal-phase Hg concentrations were similar to those of unimpacted sediments in the Midwest. Mercury to carbon ratios averaged 352 pg of HgT/mg of C and 25 pg of MeHg/mg of C and were not correlated to ionic strength. The log of the partition coefficient (log K(D)) for HgT and MeHg ranged from 3.7 to 6.4 and was typical of freshwater values determined using a 0.4 microm cutoff between the particulate phase and the dissolved phase. Log K(D) calculated using the <10 kDa fraction as "dissolved" ranged from 4.3 to 6.6 and had a smaller standard deviation about the mean. In addition, our data support the "particle concentration effect" (PCE) hypothesis that the association of Hg with colloids in the filter-passing fraction can lower the observed log K(D). The similarity between colloidal and particulate-phase partition coefficients suggests that colloidal mass and not preferential colloidal partitioning drives the PCE. PMID- 11775153 TI - Hydrogen concentrations in sulfate-reducing estuarine sediments during PCE dehalogenation. AB - Despite recent progress made evaluating the role of hydrogen (H2) as a key electron donor in the anaerobic remediation of chloroethenes, few studies have focused on the evaluation of hydrogen thresholds relative to reductive dehalogenation in sulfidogenic environments. Competition for hydrogen exists among microbial populations in anaerobic sediments, and direct evidence indicates that lower hydrogen thresholds are observed with more energetically favorable electron-accepting processes. This study examined aqueous hydrogen concentrations associated with sulfate reduction and perchloroethylene (PCE) dehalogenation in anoxic estuarine sediment slurry microcosms and evaluated the competition for H2 reducing equivalents within these systems. After an initial lag period of 13 days, PCE was reductively transformed to trichloroethylene (TCE). During the time of continuous PCE dehalogenation, a significantly (P < 0.05) lower hydrogen concentration (0.5 nM) was observed in the sediment slurries amended with PCE as compared to slurries without PCE (0.8 nM). Sulfate reduction to sulfide was observed in all sediment slurries, but in microcosms actively dechlorinating PCE, the amount of reducing equivalents directed to sulfate reduction was approximately half the amount in sediment slurries without PCE. These findings provide evidence that a lower hydrogen threshold exists in anoxic estuarine sediment slurries with PCE as a terminal electron acceptor as compared to sediment slurries in which sulfate reduction was the predominant electron accepting process. Furthermore, our results utilizing the inhibitor molybdate indicated that H2-utilizing methanogens may have the potential to effectively compete with dechlorinators for hydrogen when sulfate reduction is initially inhibited. PMID- 11775154 TI - Sorption and degradation of the herbicide 2-methyl-4,6-dinitrophenol under aerobic conditions in a sandy aquifer in Vejen, Denmark. AB - A pulse (7 days) and a continuous (216 days), natural gradient field injection experiment with herbicides, including 2-methyl-4,6-dinitrophenol (4,6-dinitro-o cresol, abbreviated DNOC), and a bromide tracer were conducted in a shallow, aerobic aquifer near Vejen, Denmark. The pulse and continuous plume were monitored in a dense, three-dimensional monitoring network installed in the aquifer downgradient of the injection. The sorption and degradation of DNOC were evaluated based on moment analysis of breakthrough curves, cross sections, and snapshots of the DNOC plume and supported by results from laboratory experiments. Significant and spatially variable sorption of DNOC (Kd range, 0.10-0.98 L/kg) was observed due to a specific binding of DNOC to clay minerals. The spatial variation was mainly a result of variation in pH, with stronger sorption at lower pH, whereas other factors such as cation composition on the solid matrix appeared to be negligible. Significant degradation of DNOC in the aquifer was revealed by moment analysis of data from the continuous field injection experiment. Degradation of DNOC in the field was slow and/or subject to long lag phases, and the data suggested spatially varying degradation potentials. This was supported by the laboratory experiments. The potential for natural attenuation of DNOC in aerobic aquifers appears promising. PMID- 11775155 TI - Alkylphenol ethoxylate degradation products in land-applied sewage sludge (biosolids). AB - Alkylphenol ethoxylates, widely used in commercial and household detergents in the United States, can degrade during the wastewater treatment process to more toxic, estrogenic, and lipophilic compounds. These include octylphenol (OP), nonylphenols (NPs), nonylphenol monoethoxylates (NP1EOs), and nonylphenol diethoxylates (NP2EOs). These compounds have received considerable attention due to their acute toxicity and ability to disrupt the endocrine system. In Europe, regulations have been established to control their impact on the environment. In this study, biosolids derived from all 11 U.S. wastewater treatment plants examined contained detectable levels of OP, NPs, NP1EOs, and NP2EOs. Nine exceeded the current Danish land application limit (30 mg/kg; sum of NPs, NP1EOs, and NP2EOs) by 6-33x. NPs were the major component, and their concentrations therein ranged from 5.4 to 887 mg/kg (dry weight). OP, reportedly 10-20x more estrogenic than NP, was detected in these same nine biosolids at levels up to 12.6 mg/kg. Three biosolids were also subjected to the U.S. Environmental Protection Agency Toxicity Characteristic Leaching Procedure Method 1311. NPs and NP1EOs were both detected in the leachate; the former at concentrations from 9.4 to 309 microg/L. On the basis of effect levels published in the literature, alkylphenol ethoxylate degradates in U.S. biosolids may cause adverse environmental impacts. PMID- 11775156 TI - Nature and transformation of dissolved organic matter in treatment wetlands. AB - This investigation into the occurrence, character, and transformation of dissolved organic matter (DOM) in treatment wetlands in the western United States shows that (i) the nature of DOM in the source water has a major influence on transformations that occur during treatment, (ii) the climate factors have a secondary effect on transformations, (iii) the wetlands receiving treated wastewater can produce a net increase in DOM, and (iv) the hierarchical analytical approach used in this study can measure the subtle DOM transformations that occur. As wastewater treatment plant effluent passes through treatment wetlands, the DOM undergoes transformation to become more aromatic and oxygenated. Autochthonous sources are contributed to the DOM, the nature of which is governed by the developmental stage of the wetland system as well as vegetation patterns. Concentrations of specific wastewater-derived organic contaminants such as linear alkylbenzene sulfonate, caffeine, and ethylenediaminetetraacetic acid were significantly attenuated by wetland treatment and were not contributed by internal loading. PMID- 11775157 TI - Interfacial mass transfer in randomly packed towers: a confident correlation for environmental applications. AB - Volumetric mass-transfer coefficients (kLa(w), KLa(w), kGa(w), kGa(w)) required for randomly dumped packed tower design were gathered from the literature to generate a working database comprehending 2675 measurements relevant to water and air pollution abatement processes. The cross-examination of two important correlations predicting mass-transfer coefficients was achieved through this database (Onda correlation, 1968; Billet and Schultes correlation, 1993). Some limitations regarding either the level of accuracy or the application range came to light with this investigation. Artificial neural network (ANN) modeling is then proposed allowing all four mass-transfer coefficients predictions. A single ANN correlation was built to predict the dimensionless gas (or liquid) film Sherwood number (ShL/G) as a function of six dimensionless groups, namely, the liquid Reynolds (ReL), Froude (FrL), Eotvos (EoL) numbers, the gas (or liquid) Schmidt number (ScL/G), the Lockhart-Martinelli parameter (chi), and a bed characterizing number (K). Using the ANN correlation and the two-film theory, a reconciliation procedure was further implemented resulting in better predictions of the gas (or liquid) overall volumetric mass-transfer coefficients. The resulting correlation yielded an absolute average relative error of 22.1% and a standard deviation of 21.1% based on whole database while the ANN predictions remain in accordance with the physical evidence reported in the literature. PMID- 11775158 TI - Accounting for source location and transport direction into geostatistical prediction of contaminants. AB - This paper presents a variant of the well-known kriging with a trend that allows one to account for the pollutant source coordinates and information about transport process into the spatial prediction of pollutant concentration. The new technique is illustrated using lead data from a Dallas metropolitan area and cadmium data from Palmerton (PA) NPL Superfund site. Instead of modeling the local spatial trend as low-order polynomials of coordinates, it is here expressed as a function of two factors that likely control the pollution spread: the distance to the smelter and the deviation from the major wind direction. Four different combinations of these two factors are developed, and their prediction performances are evaluated for a range of wind directions using cross-validation. Comparison with two traditional algorithms (OK and KT) shows that the proposed approach leads to smaller mean square errors of prediction when the correct wind direction is determined. The best combination of trend model and wind direction is site-dependent and derived using cross-validation. Kriging of residuals from a global trend model is an alternative to the use of local trends, and both techniques are shown to outperform ordinary kriging. PMID- 11775159 TI - Equilibrium partition theory applied to PCBs in macrophytes. AB - The applicability of the equilibrium partition theory (EPT) for PCB accumulation in submerged macrophyte shoots was investigated using field data. The equilibrium state of PCBs between macrophyte shoots and sediments was verified by testing the direct proportionality (slope = 1 in a log-log relationship) between congener concentrations in the lipids of macrophyte shoots (Cli) and in the organic fraction of sediments (Cso), using the slope-range method. A significant proportionality was found between Cli and Cso (slope of the log-log relationship: 0.978 +/- 0.041; R2 = 0.847; P < 0.001). The biota-sediment accumulation factor (BSAF) predicted from this relationship (3.74, SE: 1.14) was in the 1-4 range that is suggested in the literature. These results indicate that, in our study sites, EPT is applicable to PCBs in macrophyte shoots. This opens interesting perspectives in environmental monitoring. PMID- 11775160 TI - A 3D Eulerian source-oriented model for an externally mixed aerosol. AB - A 3D Eulerian source-oriented model for an externally mixed aerosol is developed and then used to compute the contribution that different emission sources make to regional fine particle concentrations in the South Coast Air Basin surrounding Los Angeles, CA, on September 25, 1996. The model simultaneously tracks fine particle concentrations (PM2.5), inhalable particle concentrations (PM10), ozone, and other gaseous pollutant concentrations yielding a tool that can be used to study the control of all of the regulated contaminants in the atmosphere within a single unified framework. Model predictions identify geographical areas that are influenced by PM2.5 associated with crustal material other than paved road dust, paved road dust, diesel engines, food cooking, noncatalyst equipped gasoline engines, catalyst-equipped gasoline engines, combustion of high sulfur-content fuel, other primary particle sources, sea salt, and marine background sulfate particles. The contribution that each of these source types makes to regional fine particle concentrations is distinct, reflecting the unique chemical composition, spatial distribution, and diurnal trends of primary emissions. The single largest contribution to regional PM2.5 in the South Coast Air Basin surrounding Los Angeles is associated with the accumulation of secondary ammonium nitrate on background marine sulfate particles. This pattern indicates that control of PM2.5 concentrations in Los Angeles must be accomplished through a program that includes both reductions in the emissions of gaseous precursors of secondary PM2.5 as well as control of primary particle emissions. PMID- 11775161 TI - Congener-independent immunoassay for microcystins and nodularins. AB - Cyanobacteria (blue-green algae) (e.g., Microcystis and Nodularia spp.) capable of producing toxic peptides are found in fresh and brackish water worldwide. These toxins include the microcystin (MC) heptapeptides (>60 congeners) and the nodularin pentapeptides (ca. 5 congeners). Cyanobacterial cyclic peptide toxins are harmful to man, other mammals, birds, and fish. Acute exposure to high concentrations of these toxins causes liver damage, while subchronic or chronic exposure may promote liver tumor formation. The detection of cyclic peptide cyanobacterial toxins in surface and drinking waters has been hampered by the low limits of detection required and that the present routine detection is restricted to a few of the congeners. The unusual beta-amino acid ADDA (4E,6E-3-amino-9 methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid) is present in most (>80%) of the known toxic penta- and heptapeptide toxin congeners. Here, we report the synthesis of two ADDA-haptens, the raising of antibodies to ADDA, and the development of a competitive indirect ELISA for the detection of microcystins and nodularins utilizing these antibodies. The assay has a limit of quantitation of 0.02-0.07 ng/mL (depending on which congeners are present), lower than the WHO proposed guideline (1 ng/mL) for drinking water, irrespective of the sample matrix (raw water, drinking water, or pure toxin in PBS). This new ELISA is robust, can be performed without sample preconcentration, detects toxins in freshwater samples at lower concentrations than does the protein phosphatase inhibition assay, and shows very good cross-reactivity with all cyanobacterial cyclic peptide toxin congeners tested to date (MC-LR, -RR, -YR, -LW, -LF, 3 desmethyl-MC-LR, 3-desmethyl-MC-RR, and nodularin). PMID- 11775162 TI - Sampling atmospheric carbonaceous aerosols using a particle trap impactor/denuder sampler. AB - A particle trap impactor/denuder system has been developed and tested for the sampling of ambient carbonaceous aerosols. Use of a particle trap impactor allows for a reduction of particle bounce and re-entrainment at high particle loadings, and operation at high volumetric flow rates is achieved without the use of oiled impaction substrates, thus facilitating the chemical and physical analysis of the organic compounds comprising the collected gas (G) and particle (P) phases. Honeycomb denuders have a greater density of channels for a given denuder cross sectional area than parallel plate or annular denuders; for a given sampling flow rate, honeycomb denuders can be fabricated in more compact shapes and will have a greater amount of surface area for the collection of gases. Field testing of the sampler was conducted primarily at night to minimize the evaporation of organic carbon (OC) from collected particles, which can result from the heating of collected particles as ambient temperatures rise during the day. In side-by-side testing with an open-face filter pack sampler, the denuder system was found to minimize positive gas adsorption artifacts caused by the adsorption of gaseous OC to quartz filter fiber (QFF) surfaces. In the denuder sampler, negligible amounts of OC were observed on a QFF placed downstream of a particle-loaded QFF, suggesting that OC detected on the backup QFF in the filter pack sampler resulted primarily from the adsorption of ambient G-phase OC rather than OC evaporated from particles collected on the front filter. Equations are presented for the evaluation of the magnitude of positive and negative sampling artifacts. Analysis of these equations indicates that the mass of OC evaporated from filter-bound particles present downstream of a denuder depends on (i) the volume of OC-free gas passed through the filter, (ii) the P-phase concentration and the P/G partition coefficients (Kp) of the compounds comprising the P-phase OC, (iii) the temperature (T) (values of Kp are inversely proportional to T), and (iv) the mass fraction of carbon in the compounds comprising P-phase OC. For these reasons, the magnitude of evaporative losses of OC in denuder samplers may vary among different sampling events. In addition, a method utilizing gas chromatography/mass spectrometry has been developed for determination of inertial impactor collection efficiency and denuder particle transmission efficiency. Using this method, only a single extraction of the sampler components is necessary, thereby reducing the number of extractions and analyses over conventional approaches by at least a factor of 2. PMID- 11775163 TI - Determination of arsenic speciation in poultry wastes by IC-ICP-MS. AB - The aromatic organoarsenic compounds 4-hydroxy 3-nitrobenzenearsenic acid (Roxarsone, ROX) or 4-aminoben-zenearsenic acid (p-arsanilic acid, p-ASA) are used as feed additives in the poultry industry for disease control and enhanced feed efficiency. While federal regulations govern acceptable As concentrations in edible tissue, elevated As concentrations occur in poultry litter, which raises concerns over repeated land application of poultry litter in agriculture. As a precursor to studying the fate of these organoarsenic compounds in soils, three speciation methodologies were developed to separate ROX and p-ASA from the more common and more toxic As species arsenate, arsenite, dimethyl arsenic acid (DMA), and monomethyl arsenic acid (MMA). The six arsenic species were separated on a Dionex AS14 column using a PO4 eluant, an AS16 column using a OH- eluant, and an AS7 column using a HNO3 eluant. While all three methods provided detection limits below 0.5 microg L(-1) for all species, detection limits were lowest for the AS16 and AS7 columns, where all detection limits were generally < 0.05 microg L(-1). The major arsenic species in a water extract of a poultry litter sample was identified as ROX by all three methods with trace concentrations of DMA and As(V) also detected. The AS14 and AS16 separations also revealed a number of unidentified As species present at low concentrations, presumably metabolites of ROX. This methodology should prove useful in identifying organoarsenic compounds and the more toxic inorganic species in soils subject to poultry litter application. PMID- 11775164 TI - Similarity of an Aroclor-based and a full congener-based method in determining total PCBs and a modeling approach to estimate Aroclor speciation from congener specific PCB data. AB - Polychlorinated biphenyls (PCBs) have entered the environment in North America as Aroclor technical mixtures. Most methods used for the determination of total PCB levels in environmental samples visually match patterns of sample peaks to those in Aroclor standards. Concern over the accuracy of Aroclor-based measurements on compositionally modified samples coupled with advancements in analytical techniques have led to congener-specific PCB analysis. In this study, the PCB data from 27 tissue samples determined by an Aroclor-based method and a full congener method were compared in terms of total PCB concentration to assess the reliability of this Aroclor technique for total PCB determination. Our data show a strong correlation between the sum of Aroclors and the total PCBs obtained from the full congener determinations. We also developed a model using the compositional data from three Aroclors (1242, 1254, and 1260) to determine the amount of compositional alteration from original Aroclor patterns in environmental samples. Full congener data, from a variety of tissue types and trophic levels, examined using this method showed that compositional modification from original Aroclor patterns increases with trophic level, with the greatest modification observed in seal and killer whale samples. This result agrees both with expectation and with what has been found in other studies. Such techniques, which connect congener-specific PCB data to Aroclor contamination, may prove useful to investigations into environmental and metabolic fate and transfer processes. PMID- 11775165 TI - Evaluation of a photoacoustic detector for water vapor measurements under simulated tropospheric/lower stratospheric conditions. AB - Although water vapor is one of the most important and certainly the most variable minor constituent of the atmosphere, accurate measurements of p(H20) with high time resolution are difficult, particularly in the cold upper troposphere/lower stratosphere. This work demonstrates that a diode laser-based photoacoustic (PA) water vapor detector is a viable alternative to current water vapor sensors for airborne measurements. The PA system was compared with a high-quality frost point hygrometer (FPH) and with a Lyman-alpha hygrometer in the pressure range of 1000 100 hPa at frost point temperatures between 202 and 216 K. These conditions were simulated in a large environmental chamberfor 14 h. Simultaneous measurements with the three instruments agreed within 6%. Nitric acid vapor interferes with the FPH measurements at low frost point temperatures but does not affect the other instruments. The sensitivity of the PA system is already sufficient for measurements in the upper troposphere, and straightforward improvements can extend its useful range above the tropopause. Rugged construction, extreme simplicity, small size, and potential for long-term automatic operation make the PA system potentially suitable for airborne measurements. PMID- 11775166 TI - Measurement of iron(III) bioavailability in pure iron oxide minerals and soils using anthraquinone-2,6-disulfonate oxidation. AB - The quinol form (AHDS) of 9,10-anthraquinone-2,6-disulfonate (AQDS) was used as a titrant to determine bioavailability of Fe(III) in pure iron minerals and several soils. AHDS oxidation to AQDS was coupled to Fe(III) reduction to Fe(ll) in biological media consisting of trace salts and vitamins, providing estimates of bioavailability consistentwith the biogeochemical mechanisms and conditions that control Fe(III) availability to iron-reducing bacteria. Iron(III) oxide sources were synthetic oxides (amorphous and crystalline) and three soils separated into two size fractions each (0-500 and 500-1000 microm). This titration gave a measurement of the amount of Fe(III) available to dissimilatory iron-reducing bacteria and was compared to hydroxylamine reduction, oxalate extraction, and biological reduction by Shewanella alga BrY. The advantage of AHDS titration over existing chemical techniques is that it can be performed at normal soil pH and ionic strength, and it allows for distinction of iron(III) oxides rendered unavailable by sorption of Fe(II) or by other pH-dependent geochemical processes. This approach also allows distinction of Fe(III) present in micropores that is not directly available to bacteria but bioavailable in the presence of an electron shuttle capable of transporting electrons into the micropores. PMID- 11775167 TI - Partitioning and interfacial tracers for differentiating NAPL entrapment configuration: column-scale investigation. AB - Research on the use of partitioning and interfacial tracers has led to the development of techniques for estimating subsurface NAPL amount and NAPL-water interfacial area. Although these techniques have been utilized with some success at field sites, current application is limited largely to NAPL at residual saturation, such as for the case of post-remediation settings where mobile NAPL has been removed through product recovery. The goal of this study was to fundamentally evaluate partitioning and interfacial tracer behavior in controlled column-scale test cells for a range of entrapment configurations varying in NAPL saturation, with the results serving as a determinant of technique efficacy (and design protocol) for use with complexly distributed NAPLs, possibly at high saturation, in heterogeneous aquifers. Representative end members of the range of entrapment configurations observed under conditions of natural heterogeneity (an occurrence with residual NAPL saturation [discontinuous blobs] and an occurrence with high NAPL saturation [continuous free-phase LNAPL lens]) were evaluated. Study results indicated accurate prediction (using measured tracer retardation and equilibrium-based computational techniques) of NAPL amount and NAPL-water interfacial area for the case of residual NAPL saturation. For the high saturation LNAPL lens, results indicated that NAPL-water interfacial area, but not NAPL amount (underpredicted by 35%), can be reasonably determined using conventional computation techniques. Underprediction of NAPL amount lead to an erroneous prediction of NAPL distribution, as indicated by the NAPL morphology index. In light of these results, careful consideration should be given to technique design and critical assumptions before applying equilibrium-based partitioning tracer methodology to settings where NAPLs are complexly entrapped, such as in naturally heterogeneous subsurface formations. PMID- 11775168 TI - Examination of cadmium(II) complexation by the Suwannee River fulvic acid using 113Cd NMR relaxation measurements. AB - Aquatic and terrestrial fulvic acids are environmentally important because they affect the bioavailability and transport of metal ions. Prior studies demonstrated that Cd(ll) binds to the oxygen containing functional groups of fulvic acids. The complexation of Cd(II) is further investigated in this study using 113Cd NMR relaxation measurements for solutions of the Suwannee River fulvic acid (SRFA). Spin-lattice (T1) and spin-spin (T2) relaxation times are measured over a range of Cd(II):SRFA ratios. The results clearly indicate two types of Cd(II) binding sites for the SRFA. A series of model ligands was also examined to gain further understanding of the two types of binding motifs present in the fulvic acid. The results for a model compound containing several carboxylate functionalities in near proximity correspond very closely to the results obtained for the strong binding sites of the Cd(II)-SRFA complexes. PMID- 11775169 TI - Use of iron oxide-coated sand to remove strontium from simulated Hanford tank wastes. AB - The ability of iron oxide-coated sand (IOCS) to adsorb strontium from synthetic wastes simulating the tank wastes at the Hanford Nuclear Reservation was examined in this study. These wastes have high pH and high ionic strength, containing up to 5.5 M Na+, 3.7 M NO3-, and 1.2 M OH-. The use of IOCS in such applications may be advantageous because it is inexpensive, is nontoxic, and can be prepared from readily available materials. IOCS can selectively remove strontium from solutions, even when they contain overwhelmingly higher concentrations of potentially competing cations such as Ca2+, Al3+, and Cr3+. Sr-EDTA chelates do not adsorb to IOCS. However, the interference caused by EDTA can be substantially overcome by the addition of excess Ca to the solution since Ca displaces Sr from EDTA. The adsorbed Sr can be released, and the IOCS can be regenerated by exposure to dilute acid (pH approximately 3) for short periods. The physical and adsorptive properties of the IOCS remain essentially unaltered over at least several dozens of regeneration cycles, corresponding to treatment of at least 20000 bed volumes of influent. The only byproduct of the regeneration process is a small volume of residual waste containing essentially only strontium and dilute acid. PMID- 11775170 TI - Pilot study of in-situ thermal treatment for the remediation of pentachlorophenol contaminated aquifers. AB - A field pilot study of a steam injection method for the treatment of pentachlorophenol (PCP)-contaminated soil and groundwater has shown potential advantages over the traditional pump-and-treatment method. Low-pressure steam was injected 10 m below the ground surface. The ground water temperature was raised to 118 degrees C over a period of 3 months. Five soil and groundwater sampling events were performed during the pilot test. Results of sample analysis showed that the PCP concentrations in deep aquifer soil decreased dramatically whereas those in shallow aquifer soil increased. It was concluded that raising the groundwater temperature caused PCP in deep aquifer soil to be desorbed, and as the hot, deep groundwater circulated upward, it brought the desorbed PCP to the shallow aquifer. By using steam injection, PCP can be desorbed from soil and moved upward to the ground surface so that it can be removed more easily through pump-and-treatment. PMID- 11775171 TI - Flocculation/flotation/ultrafiltration integrated process for the treatment of cork processing wastewaters. AB - Membrane fouling is the major problem in the treatment by ultrafiltration (UF) of the cork processing wastewaters. This problem leads to drastic reduction on the permeate fluxes and has been associated with wastewaters phenolic/tannic colloidal matter. The present work proposes a flocculation/flotation/ultrafiltration integrated process for the treatment of these wastewaters. A flocculation study was carried out in jar-test equipment with chitosan. The zeta-potential and the particle size were monitored at different pH values and for different chitosan concentrations. The results showed an increase of the zeta-potential when chitosan is added and a significant increase of the effluent particle size with the decrease of the pH. A dissolved air flotation study was performed with the flocculated wastewater. The parameters varied were the operating pressure and the recycle ratio. It was observed that for higher pressures and at a recycle ratio of 0.19 the polyphenols removal was higher. The UF experiments were carried out in flat-sheet cells of 13.2 cm2 of membrane surface area at transmembrane pressures of 1-3 bar. A commercial membrane (Ropur-TS60) and four cellulose acetate membranes with molecular weight cutoff (MWCO) ranging from 4.5 to 86 kDa were used. The flocculation/flotation pretreatment led to the enhancement of the UF permeate fluxes. For the membrane with higher MWCO, the permeate flux enhancement reached 130%. PMID- 11775172 TI - Field assessment of nanoscale bimetallic particles for groundwater treatment. AB - A field demonstration was performed in which nanoscale bimetallic (Fe/Pd) particles were gravity-fed into groundwater contaminated bytrichloroethene and other chlorinated aliphatic hydrocarbons at a manufacturing site. With diameters on the order of 100-200 nm, the nanoparticles are uniquely suited to rapidly degrade redox-amenable contaminants and for optimal subsurface delivery and dispersion. Approximately 1.7 kg of the nanoparticles was fed into the test area over a 2-day period, resulting in minimal clogging of the injection well. The test area was located within a well-characterized region of the contaminant plume and included an injection well and three piezometer couplets spaced 1.5 m apart. Despite the low nanoparticle dosage, trichloroethene reduction efficiencies of up to 96% were observed over a 4-week monitoring period with the highest values observed at the injection well and adjacent piezometers. Data from the field assessment were consistent with the results of pre-injection laboratory studies, which showed rapid dechlorination of target chlorinated compounds accompanied by a sharp decrease of standard oxidation potential and an increase in pH. PMID- 11775173 TI - Environmental impacts of PAH and oil release as a NAPL or as contaminated pore water from the construction of a 90-cm in situ isolation cap. AB - The placement of a sediment cap was the remedial alternative selected in the Record of Decision for the containment of PAH-contaminated sediments near the Wyckoff/Eagle Harbor Superfund site shoreline, a former log rafting area at this closed wood treatment site. Soft sediments with substantial quantities of nonaqueous phase liquid (NAPL) occurred in this area, which raised a concern that there would be environmental releases or potential cap failure in this area of the site. As part of the investigations to guide cap design, a laboratory bench study was devised to evaluate consolidation-driven NAPL and dissolved phase PAH permeation of the cap. Sediment cores collected from the site were extruded side by-side into 20 cm diameter, 120 cm high acrylic columns to maintain sediment stratification. Synthetic seawater was added until approximately 60 cm of water covered the site sediment. The simulated cap material was added to each column in such a manner as to fall through the overlying water at a uniform rate to simulate settling velocities expected during a barge wash-off placement event. Vertical loads were applied incrementally to the cap/sediment columns until the total consolidation stress was equivalent to a 90-cm cap. Each column was extruded, inspected visually for the migration of NAPL, and sectioned into three layers with each analyzed for total petroleum hydrocarbons and PAHs. In all three test cylinders, there was no indication of impact to the top 10 cm of the cap (the biologically active zone). The results suggest that the chemicals detected at high concentrations in the native sediments would stay in place and not migrate through a overlying cap via consolidation-induced advection. PMID- 11775174 TI - Effects of quartz addition on the mechanochemical dechlorination of chlorobiphenyl by using CaO. AB - Grinding a mixture of 3-chlorobiphenyl (BP-Cl) and CaO with or without the addition of quartz was conducted in air by a planetary ball mill to investigate the mechanochemical dechlorination of BP-Cl. The dechlorinating reaction proceeds with an increase in grinding time, and over 99% of BP-Cl is decomposed at 360 min. Washing the ground sample with different solvents results in different products. Addition of quartz to the grinding mixture facilitates dechlorination efficiency, especially in the case of a high weight ratio of BP-Cl to CaO. PMID- 11775175 TI - Effects of combustion temperature on PCDD/Fs formation in laboratory-scale fluidized-bed incineration. AB - Combustion experiments in a laboratory-scale fluidized-bed reactor were performed to elucidate the effects of combustion temperature on PCDD/Fs formation during incineration of model wastes with poly(vinyl chloride) or sodium chloride as a chlorine source and copper chloride as a catalyst. Each temperature of primary and secondary combustion zones in the reactor was set independently to 700, 800, and 900 degrees C using external electric heaters. The PCDD/Fs concentration is reduced as the temperature of the secondary combustion zone increases. It is effective to keep the temperature of the secondary combustion zone high enough to reduce their release during the waste incineration. On the other hand, as the temperature of the primary combustion zone rises, the PCDD/Fs concentration also increases. Lower temperature of the primary combustion zone results in less PCDD/Fs concentration in these experimental conditions. This result is probably related to the devolatilization rate of the solid waste in the primary combustion zone. The temperature decrease slows the devolatilization rate and promotes mixing of oxygen and volatile matters from the solid waste. This contributes to completing combustion reactions, resulting in reducing the PCDD/Fs concentration. PMID- 11775176 TI - In situ algal bloom control by the integration of ultrasonic radiation and jet circulation to flushing. AB - A novel strategy for in situ water bloom control was applied and evaluated in Lake Senba. The proposed strategy was to integrate ultrasonic radiation and water jet circulation to an existing flushing process for reducing the growth rate of cyanobacteria and to support the flushing process by providing efficient mixing. Ten units of the system, each consisting of an ultrasonication module and a water jet circulator module, were strategically situated on the lake, and the performance was monitored for 2 years. Water bloom occurrence reflected as chlorophyll a, SS, and transparency were controlled to lower levels when the integrated system was coupled with sufficient inflow water supply to achieve the target flushing rate. Also, an improvement in the water quality such as COD and phosphorus were observed. Based on linear regression analysis, relationships between water quality parameters and inflow water volume were discussed to evaluate the proposed strategy. Of the three major water quality parameters associated with water bloom, the integrated system contributed mainly to the reduction in SS and transparency compared to chlorophyll a reduction. Improved chlorophyll a reduction may be achieved by strategies that augment effective washout of cyanobacteria during flushing. PMID- 11775177 TI - Effect of cyclodextrins on surface and pore properties of soil clay minerals. AB - Although cyclodextrins are increasingly used in soil decontamination, little is known about their effects on soil physicochemical properties. In this work, the surface and pore properties of randomly methylated beta-cyclodextrin (RAMEB) and three typical clay minerals were characterized, and the effects of RAMEB concentrations on clay minerals were studied using water vapor adsorption desorption and mercury intrusion porosimetry techniques. As compared to clay minerals, for pure RAMEB very large surface area and volume of nanometer-size pores (micropores) were determined. Energy of interaction with water vapor, volume of micrometer-size pores (mesopores), and fractal dimensions in both pore size ranges of RAMEB were lower than those of the minerals. When increasing amounts of RAMEB were added to the minerals, the surface area and micropore volume decreased and adsorption energy increased. The volume of mesopores decreased after RAMEB treatments for bentonite and kaolin and increased for illite. As deduced from the fractal dimensions increase, the pore structure of the minerals became more complex with RAMEB addition. The observed changes were in general contrary to these expected when RAMEB and minerals coexist as separate, nonreactive phases and suggested strong interaction of RAMEB with clay minerals. PMID- 11775178 TI - Action and distribution of organic solvent contaminations in hydrating cement: time-resolved insights into solidification of organic waste. AB - Cementitious materials are widely used as binders both in construction and in environmental technology (e.g., for stabilization and solidification). When dealing with materials contaminated with organic solvents, it is important to have an idea about the interaction between the solvents and the hydrating cement. Here, we introduce nuclear magnetic resonance relaxometry experiments as a way to study both the influence of organic model contaminants on the hydration kinetics of cement and the distribution of the contaminant in the cement matrix during the first hours and days of hydration. All solvents were found to lead to some delay in the hydration kinetics. While nonpolar compounds only lead to a minor delay and qualitatively to the same hydrating kinetics as in an uncontaminated cement mixture, the polar solvents lead to much more pronounced delays in the hydration kinetics. For toluene contents in the low percent range, there was no indication for the formation of macroscopic liquid pockets in the hydrating cement paste. The findings are consistent with recent results on the distribution of toluene in fully hydrated concrete samples. PMID- 11775179 TI - Comment on "Environmental implications on the oxygenation of gasoline with ethanol in the metropolitan area of Mexico City". PMID- 11775180 TI - Immunoguided lymph node dissection in colorectal cancer: a new challenge? AB - Knowledge of lymphatic involvement in patients with colorectal cancer is important in surgery and in the postoperative decision-making process. Fifty eight patients with recurrent colorectal cancer underwent operation with the RIGS/(Radioimmunoguided Surgery) technology. Preoperatively, patients were injected with 1 mg monoclonal antibody (MoAb) CC49 (anti-TAG-72-tumor-associated glycoprotein) labeled with 2 mCi of iodine 125. Traditional surgical exploration was followed by survey with a gamma-detecting probe. Localization of MoAb on tumor was noted in 54/58 patients (93%). Traditional exploration identified 117 suspected tumor sites. With RIGS, 177 suspected tumor sites were detected. In 17 of the 58 patients (27.5%), at least one occult tumor site identified by RIGS was confirmed by pathology with hematoxylin & eosin (H & E) staining. This finding resulted in 16 major changes in surgical plan. RIGS performance varied between lymphatic and non-lymphatic tissue, with a positive predictive value (PPV) of 95.6% and negative predictive value (NPV) of 90% in non-lymphoid tissue compared to PPV of 40% and NPV of 100% in lymphoid tissue. In patients with tumors that localize, no RIGS activity in lymph nodes signifies no tumor, while decisions based on RIGS activity in lymph nodes requires H & E confirmation. Using this guideline, additional information acquired by RIGS can help the surgeon in making an informed decision during surgery and in planning postoperative therapy. PMID- 11775181 TI - Determinants of early and late outcome after surgery for type A aortic dissection. AB - The aim of this study was to identify the most important variables associated with early and late mortality in patients operated on for type A aortic dissection over a 15-year period. From January 1984 to March 1999, 110 patients underwent surgery for type A aortic dissection. The 88.1% of patients had an acute type A dissection (AD) and 11.8% had a chronic dissection (CD). Cardiac tamponade and shock occurred in 21.8% and 14.5% of the patients, respectively. The location of the primary intimal tear was in the ascending aorta in 70.9% of cases, in the arch in 17.2%, and in the descending aorta in 7.2%. Univariate and multivariate analyses were conducted to identify non-embolic variables independently correlated to in-hospital death. Kaplan-Meier and Cox regression analyses and hazard function for death risk were used to analyze factors influencing overall and surgical survival. The overall in-hospital mortality rate was 20.9% (23/110 patients), being 9% for CD and 21.6% for AD. Emergent procedures had an in-hospital mortality rate of 47.6%, whereas nonemergent operations had an in-hospital mortality rate of 13.7% (p < 0.01). Univariate analysis revealed 41 preoperative and operative variables, including age (years), age >70 years, remote myocardial infarction, cerebrovascular dysfunction, diabetes, preoperative renal failure, shock, cardiopulmonary bypass time (minutes), emergency operation, as factors associated to in-hospital death (p < 0.05). Stepwise logistic regression analysis for in-hospital death selected as independent predicting variables (p < 0.05) remote myocardial infarction [p = 0.006, odds ratio (OR) = 1.9], preoperative renal failure (p = 0.031; OR = 0.8), shock (p = 0.001; OR = 3.1), and age >70 years (p = 0.007; OR = 1.7). Follow-up ranged from 9 to 172 months (median 78 months), with Kaplan-Meier survivals for all the patients and hospital survivors of 42% and 54% at 10 years, respectively. Cox regression analysis has identified postoperative stroke [relative risk (RR) = 3.7; p = 0.012), intimal tear in the aortic arch (RR = 2.3; p = 0.036), and postoperative renal failure (RR = 4.5; p = 0.007) as independent predictors of reduced survival at follow-up. When this kind of analysis was performed on hospital survivors only, preoperative renal dysfunction (RR = 1; p = 0.013), reoperation (RR = 1.7;p = 0.004) and intimal tear in the aortic arch (RR = 1.2; p = 0.002) emerged as risk factors. The actuarial freedom from reoperation was 85.4% at 5 years. Multiple factors still influence early and late survival after surgery for type A aortic dissection. Preoperative renal impairment both affects early and late outcome. Early postoperative course affects late outcome in hospital survivors. The presence of the intimal tear in the aortic arch has a negative impact on late survival. PMID- 11775182 TI - Mild or moderate chronic obstructive pulmonary disease risk in elective coronary artery bypass grafting surgery. AB - A history of chronic obstructive pulmonary disease (COPD) is considered a risk factor in patients undergoing coronary artery bypass grafting (CABG) surgery. The objective of this study was to examine the impact of history of mild or moderate COPD on outcome in patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. There were no statistically significant differences regarding early postoperative complications between the groups (p > 0.05). The median duration of mechanical ventilation and ICU length of stay were 0.4 and 1 days, respectively, in the two groups. The mean (+/- SD) hospital stay was 7.8 +/- 1.6 days in the COPD group and 7.5 +/- 1.3 days in the control group (p = 0.1). The mortality rate was found 1.4% in COPD patients and 0.7% in the control group (p = 0.5). We concluded that patients with a history of mild or moderate COPD undergoing elective CABG had morbidity and mortality rates comparable with those of controls (p > 0.05). PMID- 11775183 TI - Changes in bacterial concentration in the liver correlate with that in the hepaticojejunostomy after bile duct reconstruction: implication in the pathogenesis of postoperative cholangitis. AB - Postoperative cholangitis is a frequent and unpredictable complication of unknown etiology following bile duct reconstruction (BDR), particularly for biliary atresia. This study was undertaken to correlate the growth of bacteria in the hepaticojejunostomy with that in the liver after BDR. Quantitative bacterial culture was done on the specimens taken from the liver and from the hepaticojejunostomy at 1 week (group 1, n = 7), 1 month (group 2, n = 7), and 2 months (group 3, n = 7) following BDR with Roux-en-Y hepaticojejunostomy in piglets after 2 weeks of common bile duct ligation. The histological examination of the liver and the hepaticojejunostomy, as well as serial monitoring of hemogram and liver function tests, were performed to correlate the findings with the bacterial concentration of the liver and the hepaticojejunostomy following BDR. The bacterial concentration of the hepaticojejunostomy, expressed as log10 colony-forming units per gram (log10 CFU/g) of the hepaticojejunostomy, showed a progressive decrease from 8.38 +/- 1.36 in group 1, 7.07 +/- 2.54 in group 2, to 3.56 +/- 1.31 in group 3 (p = 0.001). The log10 CFU/g of the liver also showed a progressive decrease from 5.02 +/- 1.59 in group 1, 3.16 +/- 1.56 in group 2, to 2.19 +/- 1.09 in group 3 (p = 0.006). There was a significant positive correlation of the log10 CFU/g of the liver (n = 21) with that of the hepaticojejunostomy (n = 21) following BDR (r = 0.600, p = 0.004). Most of the infectious pathogens isolated from the liver were also isolated from the hepaticojejunostomy. The changes in hemoglobin, bilirubin, albumin, and ammonia significantly correlated with the changes of the bacterial concentration of the liver. The results of the study suggests that hepatic bacterial proliferation after BDR is significantly affected by microbial overgrowth in the bilioenteric anastomosis and is associated with deteriorated liver function and hemogram. PMID- 11775184 TI - Pancreatic complications in choledochal cyst and their surgical outcomes. AB - Follow-up results were analyzed to evaluate the surgical managements of pancreatic complications such as pancreatitis and protein plug formation in patients with choledochal cysts. Sixty-two patients with choledochal cysts treated between 1976 and 1999 were reviewed. Twenty-four were children and 38 were adults. Fifty-four patients showed primary cases. Cyst excision and hepaticoenterostomy were finally performed in 56 patients. Surgical sphincteroplasty or endoscopic sphincterotomy was performed to prevent recurrent protein plugs in six patients. The follow-up period was 8.1 +/- 6.1 years. Acute pancreatitis and protein plug formation was observed in 18 (33.3%) and 11 (20.4%) of 54 patients showing primary cases, respectively. Both acute pancreatitis and protein plug formation were observed more frequently in children from 1 to 15 years of age (70.6% and 41.2%, respectively) than in adults (18.6% and 12.5%, respectively). Acute pancreatitis and/or protein plug formation developed in four (57.1%) of seven patients who underwent cystenterostomy. Protein plug formation in the residual cyst after cyst excision was observed in two patients, one of whom had undergone sphincteroplasty. Diabetes mellitus due to chronic pancreatitis developed in one patient who was diagnosed late. No other pancreatitis or protein plug recurred postoperatively in this series. Our results suggested that cystenterostomy did not resolve pancreatic complications of choledochal cysts, and that surgical sphincteroplasty was ineffective in preventing the recurrent protein plug formation in the residual duct. In conclusion, complete cyst excision and an early diagnosis are necessary to prevent the development of chronic or recurrent pancreatitis after surgery. PMID- 11775185 TI - Operative technique on nearly total gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of vagal nerve, lower esophageal sphincter, and pyloric sphincter for early gastric cancer. AB - Nearly total gastrectomy preserving the vagal nerve, the lower esophageal sphincter (LES), and the pyloric sphincter was developed as a function-preserving surgical technique to improve postgastrectomy disorders. In this paper, application criteria and technique are outlined, and postoperative quality of life was clinically investigated. Ten subjects who underwent this surgical operation (group A: 7 male and 3 female subjects at age 48 to 68 years with a mean age of 58.3 years) were interviewed to inquire about reflux esophagitis, dumping syndrome, and microgastria. Group A was compared with 20 cases of conventional total gastrectomy with D2 lymphadenectomy, excision of the lower esophageal sphincter (LES), total vagotomy, and single jejunal interposition (group B: 16 male and 4 female subjects at age 48 to 72 years with a mean age of 63.9 years). Included were cases with early cancer (M or SM1 of N0) localizing at the middle third and lower stomach, which was not applicable to endoscopic excision of gastric mucosa or partial gastric excision in M cancer, 2 cm or farther from the margin of the cancer to the esophagogastric mucosa cephalad junction and 3.5 cm or farther from the margin of the cancer to the pyloric caudad sphincter; in SM1 cancer, 4 cm or farther from the oral-side margin of the cancer to esophagogastric mucosa junction and 5.5 cm or farther from the anal side margin of the cancer to the pyloric sphincter. In excision with lymph nodes, hepatic and celiac branches bifurcating from anterior and posterior trunks of the vagal nerve were preserved. To preserve LES, the esophagus was severed at the His angle at right angle to the longitudinal axis of the esophagus. The antrum was severed at 1.5 cm from the pyloric sphincter, preserving the arteria supraduodenalis. An alternative gaster was created as a 15-cm jejunal pouch with a 5-cm jejunal conduit for orthodromic peristaltic movement, using an automatic suture instrument to complete side-to-side anastomosis of folded jejunum with 1- to 1.5-cm long upper end of the pouch not anastomosed. The abdominal esophagus was mechanically anastomosed with a jejunal J pouch, and anastomosis of the pyloric antrum with a jejunal conduit was manually completed by stratum anastomosis. In group A, food ingestion per time could be taken the same as that of a healthy person, with no reflux esophagitis and dumping syndrome being noticed. Reflux esophagitis developed more significantly in group B than in group A (p < 0.05). In food ingestion per time, group B was significantly delayed compared with group A (p < 0.05). The present results suggested that the surgical technique proposed is a function-preserving gastric surgery appropriate to prevent postgastrectomy disorder of subjects. PMID- 11775186 TI - Resection of noncolorectal and nonneuroendocrine liver metastases: late metastases are the only chance of cure. AB - Resection of liver colorectal metastases allows a 5-year survival in 25% to 35% of patients. The outcome of patients with noncolorectal metastases is unknown because of the heterogeneity of this group. The aim of this retrospective study was to evaluate predictive factors of survival in patients who underwent resection of noncolorectal and nonneuroendocrine (NCRNE) liver metastases. From 1980 to 1997, 284 patients underwent hepatectomy for liver metastases of whom 39 (25 men and 14 women, mean age 55 years) had curative resection for NCRNE liver metastases. No patients had extrahepatic disease. The primary tumors were gastrointestinal (n = 15), genitourinary (n = 12) and miscellaneous (n = 12). The mean number of metastases was 1.8, and the mean size of the lesions was 51 mm. The median disease-free interval was 27 months. Twenty patients had a major hepatectomy and 19 a minor resection, with simultaneous resection of the primary in 6 cases. Overall survival was evaluated using the Kaplan-Meier method. There was no operative mortality, and 8% morbidity. The survival at 1, 3, and 5 years was 81, 40, and 35%, respectively. Patients with a disease-free interval higher than 24 months had a greater survival rate than those with a disease-free interval of less than 24 months (100% vs. 10%; p = 0.0004). Survival was not significantly influenced by age, sex, type of primary tumor, number, size and localization of metastases, type of hepatectomy, or blood transfusion. Resection of NCRNE liver metastases should be justified for patients without extrahepatic disease and resectable metastases, especially for those who have a disease-free interval of more than 24 months. PMID- 11775187 TI - Increased insufflation pressure enhances the development of liver metastasis in a mouse laparoscopy model. AB - Despite the widespread use of laparoscopic techniques for colorectal cancer surgery, little is known about the potential risk of liver metastasis following CO2 pneumoperitoneum. We investigated the effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis in a mouse model. Six- to 7-week old male BALB/C mice were intraportally inoculated with 2 x 10(4) Colon 26 cells and randomly allocated to receive either CO2 pneumoperitoneum at different pressures (5 mmHg, 10 mmHg, or 15 mmHg), xiphoid-pubic laparotomy, or no treatment other than tumor cell inoculation. Mice undergoing pneumoperitoneum or laparotomy were then subdivided by the duration of treatment (30 minutes or 60 minutes). Cancer nodules on the liver surface from a total of 122 mice were evaluated on the 14th postoperative day. Similar to full laparotomy, CO2 pneumoperitoneum at 10 mmHg and 15 mmHg for 60 minutes, and pneumoperitoneum at 15 mmHg for 30 minutes significantly promoted the growth of cancer nodules on the liver surface. Enhancement of tumor growth was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged length of pneumoperitoneum (p = 0.53) without significant interaction (p = 0.49). These results suggest that an increased insufflation pressure promotes the growth of liver metastases as well as laparotomy in this animal model. growth of liver metastases in a mouse laparoscopy model, following different pressures and durations of CO2 pneumoperitoneum, which is used most often in laparoscopic procedures. PMID- 11775188 TI - Laparoscopic evaluation and management of nonpalpable testis in children. AB - We evaluated the outcome of children with nonpalpable testis managed and treated laparoscopically in our department over a 6-year period. One hundred nine boys aged 12 months to 14 years were included in the study; most were between the ages of 12 months and 18 months. Diagnostic laparoscopy and eventual orchiectomy were performed in 50 patients (45.8%) with atrophic testicles. A normal sized intraabdominal testicle was found in 59 patients (54.1%). Seven of the intra abdominal testicles were bilateral (6.4%), and 12 were located in the vicinity of the inguinal ring (11%). All patients underwent both the first and second stages of the Fowler-Stephens procedure, except for those whose testicles were located in the vicinity of the internal inguinal ring. They underwent an immediate one stage laparoscopic-assisted orchiopexy without difficulty. Only two patients had atrophic testicles observed in the scrotal area after the complete Fowler Stephens procedure (3.4%). The good results reported in most series establish the laparoscopic management of the nonpalpable testis as "state of the art," with results superior to those obtained with the open technique regarding morbidity, complication rate, and length of hospital stay. PMID- 11775189 TI - Total pelvic exenteration for primary local advanced colorectal cancer. AB - Total pelvic exenteration (TPE) is an ultraradical operative procedure for locally advanced pelvic tumors with high morbidity and mortality rates. We retrospectively reviewed the results of TPE for primary locally advanced colorectal cancer in terms of mortality, morbidity, and long-term survival. Of 2952 patients with colorectal cancer, 50 underwent TPE for primary locally advanced colorectal cancer between 1986 and 1995. There was one operative death (2%). The other 49 cases were entered into a retrospective study. Thirty-two cases (65%) showed involvement of one or more adjacent organs. Thirty-one patients (97%) had urologic organs invaded by tumor. The overall 5-year survival rate was 49% and the overall morbidity was 37%. The survival rate for stage II was 62%, and that for stage III was 35%; there was no survival in stage IV. Early morbidity was noted in 24% of patients; late morbidity, in 15%. TNM stage appeared to be the only independent factor for survival (p = 0.022). Our study showed that TPE can be performed with relatively low operative mortality and acceptable morbidity. With thorough preoperative evaluation and adequate surgical dissection, satisfactory outcomes for a primary locally advanced colorectal cancer can be achieved, especially at the earlier stages. PMID- 11775190 TI - Arrow wounds: major stimulus in the history of surgery. AB - To illustrate how the high incidence of arrow wounds provided a major stimulus for the development of surgery until a century ago, we conducted a literature search. Our research shows that archaic peoples developed considerable surgical skill for extraction of arrows, including thoracotomy and trephination. A classical Hindu veda describes a variety of extraction methods, and Homer's Iliad introduces the term iatros, which means "he who extracts arrows." Hippocrates of Kos and Galen, representatives of the humoral doctrine, both shunned surgical intervention and considered purulence a drainage of materia peccans (spoiled humors). Cornelius Celsus was the first to systematically differentiate removal of arrows per extractionem and per expulsionem. Celsus recommended the spoon of Diocles, an ancient surgical instrument specially designed for extraction of arrows. Paulus of Aegina favored rapid extraction, aggressive therapy, and ligature on both sides of a vessel before extraction efforts. Paulus was the first to describe a special instrument for the removal of detached arrowheads per expulsionem (propulsorium). In medieval Europe, the standard of surgery declined drastically. The classical procedure under the dominant influence of the humoral concept was to await pus before extraction and to burn the wound with boiling oil and a branding iron. Arab authors had conserved the knowledge of Celsus and Paulus, and in Europe a renewal was achieved by Ambroise Pare, who has been called the creator of modern surgery. The incidence of arrow wounds increased once more in the American West. Joseph H. Bill, a famous U.S. Army Surgeon preoccupied with arrow wounds, favored rapid extraction and aggressive therapy, and he taught recruits not to apply traction on the shaft. The principles established by Celsus, Paulus, Pare, and Bill not only mark important landmarks in the evolution of surgery but can also serve as the basis for modern treatment of arrow wounds, which still occur, although on a small scale. PMID- 11775191 TI - Radiologic evaluation of pediatric blunt renal trauma in patients with microscopic hematuria. AB - As a result of the rapid increase in medical costs, the efficacy of diagnostic imaging is under examination, and efforts have been made to identify patients who may safely be spared radiographic imaging. We reviewed the records of children who presented to our institution with suspected blunt renal injuries to determine if radiographic evaluation is necessary in children with microscopic hematuria and blunt renal trauma. We retrospectively reviewed the medical records of 1200 children (ages less than 18 years) who sustained blunt abdominal trauma and who presented to our level I pediatric trauma center between 1995 and 1997. Urinalysis was performed in 299 patients (25%). Urinalysis results were correlated with findings on abdominal computed tomography (CT). All patients had more than three red blood cells per high power field (RBC/ hpf) or gross hematuria. Renal injuries were graded according to the injury scale defined by the American Association for the Surgery of Trauma. Sixty-five patients had microscopic hematuria. Thirty-five (54%) were evaluated with an abdominal CT scan. Three patients sustained significant renal injuries (grade II-V), and 32 patients had normal findings or renal contusions. Therefore only 3 of 65 patients (4.6%) sustained a significant renal injury. All three patients had other associated major organ injuries. Of the three patients with gross hematuria evaluated with abdominal CT, one (33%) sustained a significant renal injury and had no associated injuries. The degree of hematuria did not correlate with the grade of renal injury. Pediatric patients with blunt trauma, microscopic hematuria, and no associated injuries do not require radiologic evaluation, as significant renal injuries are unlikely. However, children who present with associated injuries and microscopic hematuria after blunt trauma may have significant renal injuries and should undergo radiologic evaluation. PMID- 11775192 TI - Importance of delayed imaging for blunt renal trauma. AB - The advent of noninvasive computed tomography of the abdomen and pelvis for evaluation of blunt renal trauma has led to the practice of expectant management for hemodynamically stable patients. Although expectant management of higher grade injuries (American Association for the Surgery of Trauma Renal Injury Scale) would intuitively result in an increased frequency of urologic complications, this has not been previously examined in a large series of patients utilizing contemporary radiologic imaging techniques. A retrospective review of patients from a single institution within a recent 4-year period revealed 4 grade I, 13 grade II, 21 grade III, 7 grade IV, and 4 grade V injuries. None of grade 1, 15% of grade II, 38% of grade III, 43% of grade IV, and 100% of grade V injuries had one or more (15 major and 11 minor) urologic complications. The incidence of urinary complications correlated significantly with increasing grade (0%, 15%, 38%, 43%, and 100% for grades I to V, respectively; r = 0.94, p = 0.0158). Of the delayed urologic complications, 50% were diagnosed on follow-up imaging studies and 33% of them required intervention. Therefore we advocate repeat imaging 2 to 4 days after trauma resulting in grade III to V blunt renal lacerations to identify delayed complications that may require intervention. PMID- 11775193 TI - Grade IV renal injuries: evaluation, treatment, and outcome. AB - Of our last 2483 renal trauma patients, 113 had grade IV injuries. In most the mechanism was a penetrating injury (60%: 30% gunshot, 30% stab wounds). Associated injuries were common (80%) and hospital stays prolonged, averaging 16 days. Most of the patients (70%) required transfusion, some massively (average volume 4.4 liters, range 0-30 liters). Surprisingly, not all patients with grade IV renal injuries had gross hematuria: 25% had microhematuria, and 4% had neither microscopic nor gross hematuria. Computed tomography (CT) diagnosed the injury correctly in 100% of the patients in whom it was performed; when CT was not available, "one-shot" intraoperative intravenous pyelography (IVP) demonstrated grossly abnormal findings in 90%. Renal exploration was performed in 78%, resulting in 69% renorrhaphy and 9% nephrectomy rates in our 113 patients. Almost all those with penetrating trauma required exploration (97%), whereas only 50% of those with blunt trauma did so. The overall complication rate and kidney-specific complication rate did not differ significantly between patients who were observed and those who underwent surgery. Complications rates were similar in grade IV renal laceration patients and grade III patients. Delayed complications after hospital discharge were not seen, although follow-up was rare in this inner-city trauma population. Among the 21% of patients in whom postoperative nucleotide renal function scans were available, function was generally good (average 36%). Only patients who underwent concomitant vascular repair had poor function (below 20%). PMID- 11775194 TI - Potential uses of absorbable fibrin adhesive bandage for genitourinary trauma. AB - Fibrin sealants have become increasingly popular in nearly all surgical specialties. The absorbable fibrin adhesive bandage (AFAB) is a novel, potentially revolutionary product made from dried fibrinogen and thrombin. The AFAB appears to have excellent efficacy in producing rapid hemostasis in a variety of experimental major renal trauma models. The AFAB also appears to enhance healing of the urinary collecting system. Further study is essential to explore new urologic applications of this exciting technology. PMID- 11775195 TI - Pelvic fracture and associated urologic injuries. AB - Successful management of patients with major pelvic injuries requires a team approach including orthopedic, urologic, and trauma surgeons. Each unstable pelvic disruption must be treated aggressively to minimize complications and maximize long-term functional outcome. Commonly associated urologic injuries include injuries of the urethra, corpora cavernosa (penis), bladder, and bladder neck. Bladder injuries are usually extraperitoneal and result from shearing forces or direct laceration by a bone spicule. Posterior urethral injuries occur more commonly with vertically applied forces, which typically create Malgaigne type fractures. Common complications of urethral disruption are urethral stricture, incontinence, and impotence. Acute urethral injury management is controversial, although it appears that early primary realignment has promise for minimizing the complications. Impotence after pelvic fracture is predominantly vascular in origin, not neurologic as once thought. PMID- 11775196 TI - Radiographic evaluation of suspected bladder rupture following blunt trauma: critical review. AB - Indications for urgent radiographic evaluation of suspected bladder injuries are poorly defined. Review of the existing literature reveals that traumatic bladder rupture is strongly correlated with the combination of pelvic fracture and gross hematuria. Nearly all patients with hematuria or pelvic fracture alone do not have bladder rupture. Bladder rupture is commonly associated with suprapubic discomfort or inability to void in coherent, responsive patients. Intoxicated or unresponsive patients should warrant a higher index of suspicion for bladder injury among clinicians treating patients with pelvic trauma. Similarly, patients having neurologic or preexisting urologic co-morbidities may not manifest typical symptoms of bladder rupture. The above clinical indicators should be considered when clinicians determine the appropriateness of urgent cystography to detect bladder rupture. PMID- 11775197 TI - Current experience with computed tomographic cystography and blunt trauma. AB - We present our experience with computed tomographic (CT) cystography for the diagnosis of bladder rupture in patients with blunt abdominal and pelvic trauma and compare the results of CT cystography to operative exploration. We identified all blunt trauma patients diagnosed with bladder rupture from January 1992 to September 1998. We also reviewed the radiology computerized information system (RIS) for all CT cystograms performed for the evaluation of blunt trauma during the same time period. The medical records and pertinent radiographs of the patients with bladder rupture who underwent CT cystography as part of their admission evaluation were reviewed. Operative findings were compared to radiographic findings. Altogether, 316 patients had CT cystograms as part of an initial evaluation for blunt trauma. Of these patients, 44 had an ultimate diagnosis of bladder rupture; 42 patients had CT cystograms indicating bladder rupture. A total of 28 patients underwent formal bladder exploration; 23 (82%) had operative findings that exactly (i.e., presence and type of rupture) matched the CT cystogram interpretation. The overall sensitivity and specificity of CT cystography for detection of bladder rupture were 95% and 100%, respectively. For intraperitoneal rupture, the sensitivity and specificity were 78% and 99%, respectively. CT cystography provides an expedient evaluation for bladder rupture caused by blunt trauma and has an accuracy comparable to that reported for plain film cystography. We recommend CT cystography over plain film cystography for patients undergoing CT evaluation for other blunt trauma-related injuries. PMID- 11775198 TI - Comparison of open and endoscopic treatment of posttraumatic posterior urethral strictures. AB - The purpose of this study was to compare the invasiveness, morbidity, and outcomes of open versus endoscopic treatment of posttraumatic posterior urethral strictures. We compared two groups of men with strictures of the posterior urethra after pelvic fracture: Group I (n = 6) underwent cut-to-the-light procedures before 1995, and group II (n = 9) underwent perineal anastomotic urethroplasty after 1995. The operating time and blood loss were lower in the endoscopic group, but no other significant differences in morbidity or invasiveness were found. All six patients in group I required multiple secondary procedures: Three reached a stable voiding pattern after a mean of three interventions, two required subsequent urethroplasty, and one was lost to long term follow-up. Normal voiding was achieved in all group II patients, although two (22%) required single internal urethrotomy within 3 months after surgery. The data show the comparable morbidity of open urethroplasty and cut-to-the-light procedures and support an aggressive surgical approach for the delayed treatment of posttraumatic posterior urethral strictures. Other than a reduced operating time, endoscopic procedures offered no compelling advantage over surgical reconstruction. PMID- 11775199 TI - Management of penile amputation injuries. AB - Penile amputation is an uncommon injury resulting from self-mutilation, felonious assault, or accidental trauma. Management requires resuscitation and stabilization of the patient with particular attention to underlying psychiatric illness. Amputated tissue can be preserved under hypothermic conditions in preparation for surgical replantation. Current replantation techniques rely on microsurgical approximation of the dorsal structures and cavernosal arteries with uniformly good results. Phallic replacement may be necessary when the amputated segment is lost. Microsurgical free forearm flap phalloplasty is the current mainstay of penile replacement surgery. Although urethral complications remain problematic, the results continue to be acceptable with regard to appearance and function. A unique subset of patients sustaining amputation injury is children. Both replantation and phallic construction have been successful in children and represent an alternative to gender reassignment. PMID- 11775200 TI - Evidence of apoptotic smooth muscle cells in proliferative intima of injured arteries. AB - OBJECTIVE: To investigate the occurrence and extent of apoptosis in the course of restenosis. METHODS: The experimental models of vessel narrowness and intima thickness were established in minipigs' iliac arteries by balloon injury and specimens were retrieved on the 1st, 3rd, 6th, 12th and 30th days for dynamic observation. Apoptotic smooth muscle cells (SMCs) were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Apoptotic SMCs occurred only in the thickened intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was 1.94% +/ 0.42% on the 12th day and 1.36% +/- 0.31% on the 30th day respectively. The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology. CONCLUSIONS: Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation. The findings suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis. PMID- 11775201 TI - Treatment of in-stent coronary restenosis with excimer laser angioplasty. AB - OBJECTIVE: To evaluate the efficacy and safety of excimer laser coronary angioplasty (ELCA) with adjunctive balloon angioplasty in patient with in-stent restenosis. METHODS: ELCA was performed in 20 patients of instent restenosis. All patients were symptomatic and had class III-IV angina. ELCA was performed with the Spectranetics CVX-300 System. The laser catheter of Vittesse C (concentric) and E (eccentric) with diameter of 1.4-2.0 mm was used. RESULTS: Laser catheter crossed all stenotic stents without difficulty. The lesion length was 4.6-51.2 mm, mean 20.7 +/- 13.7 mm, including 14 lesions > 10 mm. Laser treatment alone increased minimal lumen diameter (MLD) from 0.3 +/- 0.3 mm to 1.4 +/- 0.3 mm (P < 0.0001) and improved the diameter stenosis from 88.8% +/- 10.0% to 46.0% +/- 8.0% (P < 0.0001). Adjunctive balloon angioplasty further increased minimal lumen diameter to 2.3 +/- 0.7 mm and reduced diameter stenosis to 14.2% +/- 8.2% (P < 0.0001). At follow-up (1-17 months, mean 8.9 +/- 5.7 months), 17 (85%) patients had remained asymptomatic, 3 (15%) patients had mild to moderate exertional angina, 1 (5%) patient received CABG. CONCLUSION: ELCA with adjunctive percutaneous transluminal coronary angioplasty (PTCA) is an efficient and safe technique to debulk tissue in the patient with in-stent restenosis. The incidence of procedural related complication was low and ELCA may be used as a good method for in-stent restenosis treatment. PMID- 11775202 TI - Alternation of Na(+)-Ca2+ exchange in rat cardiac sarcolemmal membranes during different phases of sepsis. AB - OBJECTIVE: To study the alteration of Na(+)-Ca2+ exchange in rat cardiac sarcolemmal membrane during phases of septic shock. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). Na(+)-Ca2+ exchange was assayed by radioactive analysis. RESULTS: Na(+)-dependent 45Ca2+ uptake was decreased by 62% 69% in late phase of sepsis, whereas it was not affected in early phase of sepsis. Na(+)-Ca2+ exchange stimulated by 5' guanylyl imidodiphosphate [Gpp (NH) p] was decreased by 65.7% in late phase of sepsis but unaltered in early phase of sepsis. Two agonists (angiotensin II and phenylephrine) coupled to Gq and a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) all inhibited Na(+)-Ca2+ exchange in late phase of sepsis. Na(+)-Ca2+ exchange activities induced by phosphorylation of Na(+)-Ca2+ exchange were decreased in late phase of sepsis, whereas inhibition of Na(+)-Ca2+ exchange by dephosphorylation was increased both in early and late phases of sepsis. CONCLUSION: The alteration of Na(+)-Ca2+ exchange during different phases of sepsis might be related to the activities of Gq, protein kinase C, and phosphorylation/dephosphorylation. PMID- 11775203 TI - The circadian rhythm of blood pressure and the effect of salt intake in salt sensitive subjects. AB - OBJECTIVE: To investigate the effect of salt intake on the circadian rhythm of blood pressure and the characteristics of ambulatory blood pressure (ABP) in salt sensitive (SS) subjects. METHODS: Twenty-three normotensive subjects and forty three patients with essential hypertension were included in this study. Salt sensitivity was determined with a chronic dietary salt loading test and an acute venous saline loading test, respectively. 24-hour ABP measurements were performed twice in normotensive subjects when they were on a high salt diet and when they had a low salt diet. Blood and urine samples were collected for measurement of plasma norepinephrine concentration (PNE), plasma renin activity (PRA), angiotensin II, aldosterone, erythrocyte sodium content and urinary sodium excretion. 24-hour ABP readings were also obtained in patients with essential hypertension when antihypertensive drugs were discontinued for at least 2 weeks. RESULTS: High salt intake attenuated the circadian rhythm of blood pressure in SS normotensive subjects, and the nocturnal decline in blood pressure was smaller in SS patients with essential hypertension than in salt-resistant (SR) patients. The level of PNE was higher and the suppression of PRA was smaller in SS subjects than in SR subjects when they had a high salt diet, and the urinary sodium excretion decreased and the erythrocyte sodium content increased significantly in SS subjects on high salt intake. CONCLUSIONS: High salt intake caused an abnormal circadian rhythm of blood pressure in SS subjects. The blunted nocturnal decline in blood pressure may be a characteristics of SS patients with essential hypertension. PMID- 11775204 TI - Mannitolum infusion on cirrhotic patients with tense ascites treated by paracentesis. AB - OBJECTIVE: To investigate whether albumin can be substituted by mannitolum in cirrhotic patients with tense ascites treated by paracentesis. METHODS: Sixty eight patients admitted to this therapeutic procedure were randomly assigned to receive intravenous albumin (36 patients) and mannitolum (32 patients) infusion. In repeated large-volume paracentesis (3-6 L/day), intravenous albumin 20 g or intravenous 20% mannitolum 250 ml were added. RESULTS: In 24 and 48 hours after paracentesis the mean value of electrolytes, liver and renal functions and various indicators of systemic circulation either in Group 1 or in Group 2 cases were found without changes (P > 0.05). As compared with that before paracentesis, the diameter of spleen vein was increased significantly (P < 0.05). The complications occurring after paracentesis were similar in both groups. CONCLUSIONS: It was suggested that paracentesis with intravenous infusion of mannitolum is an effective and safe method in treating cirrhotic patients with tense ascites. PMID- 11775205 TI - Cardiology in new millennium: what will the 21st century bring. PMID- 11775206 TI - A large scale epidemiological survey of Graves' disease in Daqing area. AB - OBJECTIVE: To study the incidence of Graves' disease and the associated factors. METHODS: Totally 100,123 people aged 15 to 79 years in Daqing area were surveyed epidemiologically. The investigation was conducted for two years. RESULTS: All 301 patients with Graves' disease were first diagnosed, with 74 (1.6@1000) males and 227 (4.1@1000) females. The total incidence was 3.0@1000, showing significant differences between ages and between occupations. Investigation of 18 associated factors for Graves' disease by using the logistic multivariate regression analysis showed the pathological factors of the virus infection history, psychological stimulation, food, drugs, family history, education and distribution. CONCLUSION: This study may suggest the theoretical evidence for prevention and treatment of Graves' disease. PMID- 11775207 TI - Epidemiologic study of the irritable bowel syndrome in Beijing: stratified randomized study by cluster sampling. AB - OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) in Beijing and its risk factors. METHODS: Phase I: a screening for IBS in Beijing area according to symptoms using both Manning (modified including constipation) and Rome criteria. 2486 subjects were studied by cluster sampling of the inhabitant groups according to a stratified design of urban, suburban and rural areas, and sample size of each area studied was in proportion to the population of the area. Selection of the inhabitant groups was made by simple random sampling. Age of subjects enrolled in the study was 18-70 years. All subjects fulfilling the selection criteria were requested to fill in a questionnaire assisted by trained doctors or medical students during the visit to their families. Phase II: an aliquot of patients who fulfilled at least the Manning criteria were further selected according to their scoring series to undergo detail clinical examination in the hospital including laboratory examination, abdominal ultrasonography, colonoscopy or/and barium enema to exclude organic disease of the colon. Prevalence of IBS of the population was then adjusted by the rate of correct diagnosis during Phase II study. Study using Minnesota Multi-Personality Indices (MMPI) was done in some cases. Probable risk factors were explored by comparing their frequencies among IBS group and non-IBS group using chi 2 and logistic analysis of multifactors. RESULTS: The adjusted point prevalence of IBS in Beijing is 7.26% according to Manning criteria, and is 0.82% according to Rome criteria. There is a higher prevalence rate in city (10.50%) than in rural areas (6.14%) by stratified analysis (P < 0.001). Male to female ratio is 1:1.15. And IBS is more common in people aged between 18-40 years (51.6%), and among the intellectuals. Our study indicated that history of dysentery (OR 3.00), exposure to cool (OR 1.55) and ingestion of cold food and raw materials (OR 1.24) may be the most important risk factors (P < 0.001), and IBS patients may have a higher tendency of psychological abnormalities. CONCLUSION: IBS is a common disorder in Beijing and should be taken into consideration in the human welfare strategy. PMID- 11775208 TI - Identification and analysis of mutations of the Wilson disease gene in Chinese population. AB - OBJECTIVE: To investigate the characteristics of mutations in exon 3-20 of Wilson disease (WD) gene and their consequences in Chinese population. METHODS: Sixty unrelated normal Chinese and forty-four unrelated WD patients were studied. Genomic DNA was prepared from peripheral blood leukocytes by a salt-out method. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently direct sequencing were used to identify the mutations and polymorphisms of WD gene. RESULTS: Ten different mutations have been found, accounting for 52% of the mutant genes. Five of them are identified as novel missense mutations. Mutations Arg778Leu, Thr935Met and Ala874Val were represented respectively in 28.4%, 6.8% and 3.4% of WD chromosomes. The remaining mutations were found rare and limited to one or two patients. A total of 11 patients were homozygous for a single mutation, and 17 patients were in a compound heterozygous state with or without a known mutation. CONCLUSION: In Chinese, WD seems to result from two or three relatively common mutations and a large number of rare mutations. Arg778Leu and Thr935Met might be hotspots of mutation in Chinese population. The results indicated that the feature of mutations of WD gene is different between Chinese and the Western. Instead of exon 14 and exon 18, we had to select exon 8 and exon 12 first to detect mutations of WD gene in Chinese. It is of great importance to establish a direct diagnostic method for WD. This study improves our knowledge on functional domains of the WD gene, and helps elucidate the wide spectrum of manifestations of the disease as well. PMID- 11775210 TI - Effect of Q-switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota. AB - OBJECTIVE: To investigate the effect of Q-switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota. METHODS: Multiple biopsies were carried out on 4 patients with nevus of Ota before and after laser irradiation. Altogether 11 samples were examined under light microscope and 14 under transmission electron microscope. RESULTS: Immediately after laser irradiation, the dermal melanocytes were destroyed, the melanosomes were degenerated with central vesicle formation within most of them, and intradermal round vacuoles appeared. The epidermis remained intact. Three months to 1 year after irradiation, the degenerated melanosomes and cell debris were scavenged mainly by macrophages. Dermal melanocytes gradually decreased. No fibrosis was found. CONCLUSION: Q-switched alexandrite laser can selectively destroy dermal melanocytes of nevus of Ota and treat the disease safely. PMID- 11775209 TI - Cloning of Chinese obese cDNA and its expression in E. coli. AB - OBJECTIVE: To obtain the sequence of Chinese obese (OB) cDNA and establish a method of leptin production in China. METHODS: Han Chinese OB cDNA fragment was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) with total RNA extracted from human adipocytes and was inserted into the expressing vector pBV220. Then the constructed recombinant plasmid pBV220-OB was transformed to E. coli DH5 alpha for leptin expression. The recombinant expressing system was confirmed by restriction endonuclease digestion, DNA sequencing and protein expression. E. coli cells were lysed by high-pressure homogenization. After cell membrane was extracted, the inclusion bodies were mainly renatured and purified primarily by precipitation with ammonium sulfate and gel chromatography through a Sephadex G75 column. The activity of recombinant leptin was determined by its influence on the satiety and weight gain of mice. RESULTS: Analysis of DNA sequence showed that Han Chinese OB cDNA included the glutamine codon at 49. The amount of recombinant leptin expressed in E. coli accounted for 31%-47% of total cellular proteins. From 1 L of fermentative bacteria about 40 mg of pure recombinant human leptin was isolated with a purity of being above 95%. The recombinant human leptin could reduce food intake and inhibit weight gains in mice. CONCLUSION: The glutamine codon at 49 is not missing in Chinese OB gene. The biologically active human leptin can be obtained by a relatively simple method of recombinant DNA technology. PMID- 11775211 TI - Association between delayed cardioprotection of aged rat myocytes and activation of mitogen-activated protein kinase. AB - OBJECTIVE: To study the cardioprotective effects of hypoxic preconditioning (HPC) on aged rat ventricular myocytes and the cellular mechanism of protection. METHODS: In the model of hypoxia/reoxygenation (H/R) of isolated ventricular myocytes of aged rat, the effects of HPC on aged rat ventricular myocytes against lethal H/R stimulated ischemia/reperfusion (I/R) injury 24 hours later and the changes of mitogen-activated protein kinase (MAPK) system were observed in the present study. RESULTS: HPC attenuated the lactate dehydrogenase (LDH) release and ATP depletion in myocytes and increased the viability of myocytes. It was also found that MAPK and its down-stream kinase--S6 kinase were also activated after HPC. CONCLUSION: There is delayed cardioprotection in cardiac myocytes of aged rat and the cellular mechanism underlying might involve the activation of MAPK system. PMID- 11775212 TI - Fractionated radioimmunotherapy using low doses of iodine-131 labeled anti-CEA monoclonal antibody after tumor volume reduction. AB - OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied comparatively. METHODS: A total of 200 inbred mice received tumor implantation from a murine adenocarcinoma cell line. The mice were randomly grouped to give saline, Arc-a, 131I-C50 in single or fractionated doses, cold C50, or non-specific 131I-IgG with or without surgical removal of the implanted tumor xenograft. RESULTS: In comparison to controls, animals receiving Arc-a and radioactive agents had longer survival, smaller tumor, better clinical condition, and less metastases foci. The best therapeutic response was noted after fractionated doses of 131I-C50, which showed better results in every aspect than those treated with other modalities. The favorable outcome was even more pronounced after tumor volume reduction. CONCLUSIONS: Fractionated dosing may improve the deposition of radiolabeled monoclonal antibody (McAb) and provide the best therapeutic effect on implanted tumor and metastases. Thus fractionated radioimmunotherapy (RIT) after tumor volume reduction might be a practical method with promising therapeutic results. PMID- 11775213 TI - The role of membrane potential and calcium kinetic changes in the pathogenesis of vascular hyporeactivity during severe shock. AB - OBJECTIVE: To determine the role of membrane potential and intracellular calcium kinetic changes in producing vascular hyporeactivity during severe hemorrhagic shock. METHODS: Rats were subjected to hemorrhagic shock (HS) for 2 hours. The spinotrapezius muscle was prepared for microscopy and the responses of arterioles in the muscle to norepinephrine (NE) were tested. The resting membrane potentials of isolated arterial strips were measured with a microelectrode. Membrane potential and intracellular Ca2+ ([Ca2+]i) changes in isolated arteriolar smooth muscle cells (ASMCs) were determined with fluorescent probes and a confocal microscopy. RESULTS: The arteriolar resting membrane potential was decreased from -36.7 +/- 6.3 mV in control to -29.2 +/- 5.3 mV concurrent with the increase of vasoreactivity to NE at 20 minutes after HS. At 120 minutes post-HS, the resting potential hyperpolarized to -51.9 +/- 9.1 mV, and NE stimulated [Ca2+]i increase was reduced to 50% of the control values during the appearance of arteriolar hyporeactivity, i.e. the NE threshold of the arteriolar response increased 15 fold 2 hours after the onset of hemorrhage as compared with normal animals. The state of vasoreactivity was closely related to the resting potential of vascular smooth muscle in hemorrhagic shock, with a correlation coefficient of 0.96. Treatment with glybenclamide, a selective blocker of ATP-sensitive K+ (KATP) channels, decreased the resting potential, increased NE-stimulated [Ca2+]i increase, and partially restored vasoreactivity in severe hemorrhagic shock. CONCLUSION: The results suggested that membrane hyperpolarization and the reduction of NE-stimulated [Ca2+]i increase in smooth muscle cells appeared to contribute to the vascular hyporeactivity in hemorrhagic shock. The mechanism is likely to involve in KATP channels. PMID- 11775214 TI - A study of Hodgkin/Reed-Sternberg cells using single cell polymerase chain reaction. AB - OBJECTIVE: To investigate the characteristics of Hodgkin/Reed-Stemberg (H/R-S) cells found in patients with various types of Hodgkin's disease (HD). METHODS: H/R-S cells were micropicked from frozen sections of tissues affected by HD. The DNA from these cells was amplified by polymerase chain reaction (PCR) using immunoglobulin heavy chain gene FR III a/JH primers and light chain gene family specific primers. RESULTS: A total of 52/135 (35.8%) isolated cells showed the specific products in the reactions. IgH and V kappa 4 rearrangements were repeatedly found in many cells from a lymphocyte predominance type sample; repeated V kappa 4 and individual IgH/V kappa 2,4 rearrangements and individual IgH, V lambda 3/ V kappa 4 rearrangements were found in two different cases of the nodular sclerosis type; repeated IgH/ V lambda 3 and individual V lambda 2,4 rearrangements, repeated V kappa 2,4 rearrangements, repeated V kappa 4 and individual IgH/ V kappa 3 rearrangements, repeated IgH and individual V kappa 3/ V lambda 4 rearrangements were detected in 3 cases of the mixed cellularity type. Repeated and individual IgH rearrangements were found in other 2 cases. CONCLUSION: The H/R-S cells isolated from the lymphocyte predominance subtypes of HD have IgH and V lambda 4 gene rearrangements. This suggests that the lymphocyte predominance type is a proliferation of neoplastic B cells. The cells isolated from the mixed cellularity and nodular sclerosis types derive from B lineage cells at various stages of differentiation because of the presence of their IgH, kappa and/or lambda gene rearrangements. To our knowledge, this is the first time that the lambda gene rearrangement was detected in H/R-S cells. PMID- 11775215 TI - Neuroendocrine differentiation in ovarian mucinous tumors. AB - OBJECTIVE: To investigate the relationship between neuroendocrine differentiation in ovarian mucinous tumors and its genesis. METHODS: A morphologic study of seventy-three cases of ovarian mucinous tumors (32 benign, 20 borderline, 21 malignant) using immunohistochemical and immunohistochemical/histochemical double staining techniques. RESULTS: The study showed that in tumors of benign, borderline and malignant types, the incidence of chromogranin A (CgA) positive cells was 62.5%, 75%, 76% and that of 5-hydroxytryptamine (5-HT) positive cells was 31.3%, 40% and 39%, respectively. Neuroendocrine cells (NEC) were not evenly distributed in any tumor. In four cases of the benign tumors, the number of CgA positive cells was more than 30 percent, localizing between the glandular basement membrane and the mucinous epithelial cells, with many intermediate cells containing both CgA and periodic acid-schiff (PAS) positive granules. CONCLUSION: The occurrence of both neuroendocrine and exocrine granules within the same cell has been previously described as "intermediate" in pancreatic hyperplasia, pancreatic tumors and lung signet-ring cell carcinoids. This has not previously been observed in benign ovarian mucinous tumors. Finding both endocrine and exocrine granules within a single cell seems to indicate a histogenetic relationship between the ovarian endocrine and exocrine cells. The four cases of the benign tumors might be originated from a common stem cell, such as the so called amphocrine cell. The relationship between these four tumors and neuroendocrine differentiation in ovarian mucinous tumors needs to be further clarified. PMID- 11775216 TI - Increased expression of intercellular adhesion molecule-1 in mouse focal cerebral ischemia model. AB - OBJECTIVE: To quantitatively measure the temporal profiles of intercellular adhesion molecule-1 (ICAM-1) protein in mouse brain after middle cerebral artery occlusion (MCAO). METHODS: Adult male CD-1 mice received 0, 3, 6, 12, 24, 48 and 72 hour(s) of permanent MCAO with an intraluminal suture technique. The degree and the extent of occlusion were determined using a laser Doppler flowmeter. ICAM 1 positive expression in ischemic regions was determined immunohistochemically and ICAM-1 protein was quantitatively measured using immunoprecipitation and Western blot analysis. RESULTS: After MCAO, surface cerebral blood flow (CBF) in the ischemic hemisphere decreased to 9%-15% of the baseline in each time point of 7 to 8 animals. There were no significant differences in CBF measurement during occlusion between groups. Immunohistochemistry showed that ICAM-1 positive microvascular endothelial cells were observed both in the ischemic core and in the perifocal region. There was a tendency for increasing expression of ICAM-1 positive microvascular endothelial cells from the ischemic core to the ischemic margin. Western blot analysis showed that ICAM-1 expression in the ischemic hemisphere began to increase 3 h after MCAO, peaked at 6 h to 12 h, and persisted to 72 h. CONCLUSIONS: ICAM-1 expression increases in mice with permanent MCAO because ICAM-1 can mediate leukocyte-endothelial adhesion and progression of leukocyte infiltration after permanent focal cerebral ischemia. ICAM-1 is one of the important factors participating in ischemic cerebral damage and pathogenesis of stroke. PMID- 11775217 TI - The mutation of insulin receptor substrate-1 gene in Chinese patients with non insulin-dependent diabetes mellitus. AB - OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700-(+)4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. RESULTS: Two amino acid variations [GGG-->AGG (G971 R) and CCT-->TCT (P1079 S)] and 3 silent mutations [GAT-->GAC(D422D), CCA- >CCC(P737 P) and GCA-->GCG (A804 A)] were identified, among which the CCA- >CCC(P737 P) and CCT-->TCT(P1079S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA-->GCG(A804A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, chi 2 = 18.42, P < 0.01). The most common polymorphism in the Chinese population was GCA-->GCG (A804A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, chi 2 = 8.84, P < 0.01). The homozygotes of the variation in patients with NIDDM and control subjects were 8.8% and 1.5%, respectively (chi 2 = 2.41, P > 0.05). CONCLUSION: These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM. PMID- 11775219 TI - Progress in malaria control in China. AB - PURPOSE: To summarize the main achievements of the control of malaria in the People's Republic of China. DATA SOURCES: The data are from national case reporting system (1955-1998), and bibliographic reviews of textbooks and review articles. STUDY SELECTION: Successes in control and research of malaria were identified and selected to address the stated purpose. DATA EXTRACTION: In the past 50 years, large-scale malaria control activities were conducted in the country, relying on primary health care networks and community participation. The control of malaria was implemented according to the time- and locality-oriented approaches. As a result, remarkable success has been achieved. By the end of 1998, there were 31.3 thousand malaria cases in China, with a morbidity of 0.25 per ten thousand, which dropped by 99% in comparison with that in the 1950s. RESULTS: Most of the original hyper-endemic areas became meso- or hypo-endemic and for most of the previously meso- or hypo-endemic areas, the disease became sporadic. Malaria distribution and epidemic pattern also demonstrated great changes. CONCLUSIONS: Malaria control in China has been considerably successful in the past 50 years, which coincides with the target of the World Health Organization's "Health for all by the year 2000". PMID- 11775218 TI - Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide. AB - OBJECTIVE: To study the biological effect of arsenic trioxide (As2O3) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. METHODS: SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were established by transfecting SiHa cells with Bcl-2 expression vector. The sensitivities of SiHa and SiHa-Bcl2 cells to As2O3 were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. RESULTS: As2O3 inhibited the growth of SiHa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-Bcl2 cells partly resisted As2O3 induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c myc gene expression. Nevertheless, As2O3 at a high concentration could still induce apoptosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightly inhibiting viral gene expression. CONCLUSION: As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As2O3 induced apoptosis, but the exact mechanism is unclear. PMID- 11775220 TI - Successful retrieval of intracoronary lost balloon-mounted stent using a small balloon. PMID- 11775221 TI - Pharmacotherapy for erectile dysfunction. AB - OBJECTIVE: To review current pharmacologic treatment options for erectile dysfunction. METHODS: Relevant literatures from the past two decades regarding the following treatments were reviewed: intracavemous injection, topical therapy, transurethral therapy and oral drugs. STUDY SELECTION: More than 125 originally identified articles were reviewed, and 45 were selected that especially addressed the stated purpose. RESULTS: Among the pharmacologic treatment options available, intracavemous injection therapy remains the most effective although the drop-out rate is high. Topical creams and gels have not been very successful. Transurethral alprostadil can be more effective if a constriction device is applied at the base of the penis. Oral sildenafil has the highest patient acceptance rate although systemic side effects can be a major drawback. CONCLUSIONS: Effective pharmacotherapies for ED of various etiologies are now available. However, proper evaluation of every patient should be performed before giving treatment so that a number of potentially life-threatening causes of erectile dysfunction would not be missed. PMID- 11775222 TI - Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China. AB - OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China. PMID- 11775223 TI - Relationship between metabolic phenotype of N-acetylation and bladder cancer. AB - OBJECTIVE: To study the relationship between metabolic phenotype of acetylation and bladder cancer. METHODS: Totally 203 healthy volunteers and 67 patients with bladder cancer were investigated with caffeine as a metabolic probe. Urine samples were collected in 2-6 hours after a cup of 140 mg coffee was taken, and the caffeine metabolites, 5-acetylamino-6-formylamino-1-methyluracil (AFMU) and 1 methylxanthine (1X) were analyzed by high performance liquid chromatography (HPLC). The frequency histogram and probit plot were constructed to select the critical value which was used to assess slow and fast acetylation status both in healthy volunteers and patients with bladder cancer. RESULTS: The peak height ratios of AFMU and 1X (AFMU/1X) were from 0.06 to 6.50 for healthy volunteers and 0.10 to 6.31 for patients with bladder cancer, both with the critical value of 1.10. Of 203 healthy volunteers involved in this study, 26.3% were slow acetylacors, as compared to 46.3% with slow acetylacors in patients with bladder cancer. The odds ratio is 2.376, and the gene frequency for healthy volunteers and patients with urinary bladder cancer were 0.5218 and 0.6804, respectively. CONCLUSIONS: N-acetylation status in the Chinese population is polymorphic and completely concordant with that determined with other metabolic probes. Slow acetylators are significantly associated with bladder cancer. PMID- 11775224 TI - Different Wnt-5A gene expressions in the renal cell carcinoma GRC-1 cell line during the cell cycle. AB - OBJECTIVE: To investigate the gene expression at transcription level of growth factor Wnt-5A in different phase during the cell cycle. METHODS: We synchronized the renal cell carcinoma GRC-1 cell line by double thymidine blocks and high pressure N2O gae methods and amplified Wnt-5A cDNAs from different phase using Semi-quantitative RT-PCR (reverse transcriptase polymerase chain reaction). The PCR products were electrophoresized on the agrose gel and detected by Gel Doc 1000 computer controlled system integrating the volumes of each band, representing the intensities of all pixels in a defined band. RESULTS: The different mRNA expressions of growth factor Wnt-5A was detected in RCC GRC-1 cell line. In S phase, the highest level of Wnt-5A transcript was observed, and in G1 and M phase, medial and lowest, respectively. The differences between S and M stages were statistically significant (P < 0.05). CONCLUSION: Growth factor Wnt 5A has the potential effect on tumorigenesis. It contributes to all phases during cell cycle but in S phase especially. PMID- 11775225 TI - Astragalus mongholicus and Angelica sinensis compound alleviates nephrotic hyperlipidemia in rats. AB - OBJECTIVE: To investigate the mechanism of lipid-lowering effect of the Astragalus mongholicus and Angelica sinensis compound (A&A) on nephrotic hyperlipidemia in rats. METHODS: Rats with nephrotic syndrome from accelerated nephrotoxic serum nephritis were used. They were divided into two groups: A&A treatment group and nephrotic control group. Normal rats were used as a normal control group. Serum lipids, serum lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) were assayed biochemically and enzymatically. mRNAs of hepatic hydroxy-methyl glutaryl-CoA reductase (HMG-CoA-R) and low density lipoprotein receptor (LDL-R) were assessed by Northern blot. RESULTS: In nephrotic control group hyperlipidemia was found. The activities of serum LPL and LCAT were low. Hepatic HMG-CoA-R mRNA increased temporarily at the early stage while LDL-R mRNA decreased gradually. In A&A treatment group, serum total cholesterol (TC), triglyceride (TG), low-density lipoproteins (LDL) and very low density lipoproteins (VLDL) were significantly lower than those in nephrotic control group. There was no change in the amount of hepatic HMG-CoA-R mRNA, but hepatic LDL-R mRNA and activities of serum LPL and LCAT increased significantly. CONCLUSIONS: A&A alleviates hyperlipidemia considerably in nephrotic rats. A&A improves disorders of lipid metabolism perhaps through up-regulating the expression of hepatic LDL-R gene and through increasing the activities of serum LPL and LCAT. PMID- 11775226 TI - Synergetic effect of dialyzer membrane and lipopolysaccharide on peripheral blood mononuclear cell cytokine production in uremic patients. AB - OBJECTIVE: To investigate the effect of lipopolysaccharide(LPS) and dialyzer membrane on cytokine gene expression and protein production in uremic patients on continuous ambulatory peritoneal dialysis (CAPD) and regular hemodialysis(HD). METHODS: Interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL 1Ra) produced by cultured peripheral blood mononuclear cells (PBMC) after exposure to cuprammonium (Cup) membrane, polysulfone (PS) membranes or endotoxin were detected using enzyme-linked immunoabsorbent assay. mRNA expression was determined simultaneously by in situ hybridization. RESULTS: In the absence of endotoxin, a small amount of IL-1 beta and IL-1 Ra was produced by PBMC harvested from HD and CAPD patients after incubation with Cup or PS during subsequent 24 hour culture. For healthy controls, IL-1 beta was barely detectable just above the detection limit. Although no differences could be found in protein synthesis between Cup and PS, in situ hybridization showed that Cup induced markedly higher level mRNA coding for IL-1 beta and IL-1Ra. In contrast, when subsequently stimulated with endotoxin, PBMC incubated with Cup could produce significantly larger amount of IL-1 beta and IL-1Ra compared with either unstimulated cells or post-incubation PBMC with PS. LPS-stimulated PBMC in healthy subjects produced similar amount of IL-1 beta and markedly lower IL-1Ra as compared with uremic patients on HD and CAPD. CONCLUSIONS: Two steps are required in healthy control for IL-1 beta and IL-1Ra production: induction of mRNA transcription by membrane contact, followed by LPS-induced translation, while in uremic patients on HD or CAPD bioincompatibility-membrane and LPS have a synergetic effect on IL-1 beta and IL-1Ra production. There exists an unbalance between IL-1 beta and its specific inhibitor in maintenance dialysis patients. PMID- 11775227 TI - Embolic events in 93 elderly Chinese patients with atrial fibrillation. AB - OBJECTIVES: To evaluate the prevalence of embolic events and relevant factors in elderly Chinese patients with atrial fibrillation(AF), and to provide evidence on ways to prevent embolic events. METHODS: Autopsy data from ninety-three continous elderly Chinese patients with AF were analysed. The incidence of embolic events and its relationship to underlying disease, pathologic changes in the heart, and other clinical characteristics were examined. RESULTS: Embolism were observed in 27 of 93 cases, with an incidence of 29.03%. The incidence of embolic events was higher in elderly patients with rheumatic heart disease than those with coronary artery disease, hypertensive myocardiopathy and heart diseases. Patients with chronic AF, with a course of AF > or = 3 years, and those with heart failure or diabetes had a higher incidence of embolic events than those without these complications. There was significant difference in incidence between paroxysmal and chronic AF. Patients with left atrial or ventricular enlargement, mural thrombosis in cardiac chambers, valvular calcification and valvular vegetation also had a higher incidence of embolic events. Oral dipyridamole (75-150 mg/d) or aspirin (50-150 mg/d) showed no definite effects in preventing embolism in some patients. CONCLUSIONS: There was a high incidence of embolic events in elderly Chinese patients with AF. Anticoagulation therapy should be provided to the elderly patients with AF, especially to the patients with risk factors for embolism. PMID- 11775228 TI - Relationship between expression of type III collagen and phenotype of vascular smooth muscle cells in neointimal of stented coronary artery. AB - OBJECTIVE: To investigate the secretive features of type III collagen in restenosis of the stented coronary artery and the relationship between the expression of type III. collagen and vascular smooth muscle cells (VSMCs). METHODS: An animal model of restenosis was established by implanting oversized tantalum stents into the coronary arteries in 26 dogs. At the 7th, 14th and 28th days after implantation, the stented coronaries were harvested. Transmission electronic microscopy and immunohistochemistry were employed to investigate the features of type III collagen secretion and VSMCs' phenotype. The expression of type III collagen was quantified and compared for the three stages. RESULTS: Migration and proliferation of VSMCs were the main features at the 7th day after injury. At the 14th day, proliferation of VSMCs reached the peak while much more secretion of collagen was noticeable. VSMCs began to transform from the synthetic phenotype to the contractile phenotype at the 28th day, when a great quantity of collagen was also secreted. The quantity of secreted type III collagen was greater at the 14th and 28th day than that at the 7th day (P < 0.05). The stain density of type III collagen was positively correlated to neointimal thickness at both of 14th and 28th day. CONCLUSION: The pathological bases of restenosis are variant in different period of restenosis formation. Type III collagen may play an important role in the late stage of restenosis after coronary stenting. PMID- 11775229 TI - Effect of intravenous nitroglycerin on hemodynamics in infants and children with congestive heart failure. AB - OBJECTIVE: To understand the effect of intravenous nitroglycerin (NTG) on hemodynamics in infants and small children with congestive heart failure secondary to congenital cardiac defect of left to right shunt. METHODS: Heart rate, blood pressure and total peripheral resistance were monitored continuously. Echocardiography was used to measure ejection fraction, fractional shortening, end-diastolic volume index of left ventricle, pulmonary capillary wedge pressure, pulmonary artery mean pressure and left ventricular wall stress before the use and during 0.5, 1.0, 1.5, 2.5, and 5.0 micrograms.kg-1.min-1 dosages of nitroglycerin (NTG). RESULTS: There was no significant difference in the indexes of heart rate, blood pressure, ejection fraction and fractional shortening of left ventricle, stroke volume index, cardiac output index, end-diastolic volume index before the use and after the use of NTG. Pulmonary capillary wedge pressure decreased from 15.5 +/- 2.3 mm Hg before the use of NTG to 14.3 +/- 2.2 mm Hg after the use of 0.5 microgram.kg-1.min-1 NTG (P < 0.05), minimum to 12.3 +/- 2.4 mm Hg; left ventricular wall stress I, II and III decreased from 407 +/- 65 dyn.cm-2.10(3), 166 +/- 48 dyn.cm-2.10(3), 255 +/- 52 dyn.cm-2.10(3) to 357 +/- 75 dyn.cm-2.10(3), 136 +/- 48 dyn.cm-2.10(3), 218 +/- 52 dyn.cm-2.10(3) (P < 0.05), minimum to 321 +/- 50 dyn.cm-2.10(3), 114 +/- 42 dyn.cm-2.10(3), 187 +/- 42 dyn.cm-2.10(3), respectively. Total peripheral resistance and pulmonary artery mean pressure were decreased when the dosage of intravenous NTG was increased to above 2.5 micrograms.kg-1.min-1 (P < 0.05). There was no statistical difference in the above indexes of the different dosages. CONCLUSION: Congestive heart failure secondary to congenital cardiac defect of left to right shunt in infants and small children is the indication of using intravenous NTG which could improve hemodynamics. There was different selectivity in dosage between arterial and venous vasodilatation, and the change in hemodynamics was independent of dosage. The dosages of 0.5-1.0 microgram.kg-1.min-1 NTG are recommended when the decrease of cardiac preload is the main point of therapy of heart failure. PMID- 11775230 TI - Safety and immunogenicity of lyophilized, live attenuated hepatitis A vaccine in non-human primate model. AB - OBJECTIVE: To evaluate the safety and immunogenicity of lyophilized, live attenuated hepatitis A vaccine (H2 strain) in rhesus monkeys. METHODS: Nine adult rhesus monkeys were used as experimental animals. The rhesus monkeys without anti HAV were divided randomly into the aqueous vaccination group (4 rhesus monkeys), the lyophilized vaccination group (3 rhesus monkeys), and the control group (2 rhesus monkeys). Monkeys were inoculated by intramuscular injection, with control monkeys being inoculated with Minimum Essential Medium Eagle (MEM). Following vaccination, the monkeys were observed for the development of diarrhoea and other adverse side-effects, such as changes in appetite, frequency of defaecation and stool consistency for seven days. At the weeks 2, 3, 4, 6, 8, 10 and 12 positnoculation, the peripheral blood was collected from all animals and assayed for anti-HAV and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), at weeks 0, 4 and 8 postinocuation, needle-biopsy specimens were taken at weeks 0, 4, 8 and 12, all monkeys were sacrificed and tissue samples were taken from liver, lung, heart, kidney and brain for pathological examination at week 12. RESULTS: Animals were immunized with a dose of 7.0 logTCID50/ml which is stable after freeze-drying. During the 12-week observation, no animals showed abnormal elevations of liver enzymes (ALT and AST) and no change in appetite or activity. Two monkeys (one in the aqueous group and the other in lyophilized group) showed possible lesions at week 8. The lyophilized vaccine, in addition to eliciting an anti-HAV IgG response similar to aqueous vaccine (P > 0.05), also showed IgM anti-HAV response at week 2 which was not observed with aqueous vaccine. CONCLUSIONS: These results demonstrate that lyophilized, live hepatitis A vaccine is safe and highly immunogenic in primates, supporting its further evaluation in human clinical studies. PMID- 11775231 TI - Induction of intestinal metaplasia in stomach of dogs and expression of tumor related proteins in animal gastric mucosa lesions. AB - OBJECTIVE: To observe the development and progression of intestinal metaplasia (IM) in dog's stomach and expression of tumor-related proteins in gastric mucosa lesions. METHODS: IM animal model was induced in stomach of Beagle dog by combining treatment of oral administration of N-methyl-N'-nito-N-nitrosoguanidine (MNNG) and ranitidine (R) with X-ray irradiation to the target organ. Expression of APC, p53, K-ras and bcl-2 gene proteins in animal gastric mucosa lesions were determined with immunohistochemical method. RESULTS: IM animal model was successfully induced and the dynamic pathological changes were observed by means of this model. It was confirmed that the progression from normal epithelial cells to IM cells may require several stages, including superficial gastritis, chronic atrophic gastritis, slight focal IM and moderate or severe IM. Aberrant bcl-2 protein can be detected in the atrophic mucosa epithelium and the abnormal expression of APC, K-ras and bcl-2 can be found in IM of mucosa. CONCLUSIONS: IM model in stomach of Beagle dog can be successfully induced by our method (MNNG + R + X-ray). The progression from normal to IM in dog resembles that of human being and the expression of tumor-related proteins (APC, bcl-2, K-ras) may play a role in the malignant transformation of IM. PMID- 11775232 TI - Gene polymorphism in apolipoprotein E and presenilin-1 in patients with late onset Alzheimer's disease. AB - OBJECTIVE: To evaluate the association of apolipoprotein E (apoE) and presenilin 1 (PS-1) gene polymorphism with late-onset Alzheimer's disease (AD). METHODS: A case-control study was undertaken to detect the polymorphism of apoE and PS-1 by polymerase chain reaction and digestion with the endonucleases of BspL I, Hha I and BamH I. RESULTS: The frequencies of apoE epsilon 3/4 genotype and epsilon 4 allele in late-onset AD (n = 42) were significantly higher than those of age matched controls (P < 0.05). The frequencies of the apoE intron 1 enhancer (IE1) G/G genotype and G allele in late-onset AD were also significantly higher than those in controls (P < 0.05). The frequencies of the PS-1 1/1 genotype but not the 1 allele in AD were significantly higher than those in controls (P < 0.05). The apoE epsilon 4 allele was associated with a tripling of risk for late-onset AD compared with that with no epsilon 4 allele (odds ratio: 2.932). Homozygosity of the G allele in IE1 and 1/1 genotype in PS-1 was associated with a doubling of risk for late-onset AD, and odds ratios were 2.223 and 2.066, respectively. When the apoE epsilon 4 was controlled, the association between the IE1 G/G genotype AD was no longer statistically significant (P > 0.05). We sequenced the exon 4 of apoE in patients with late-onset AD, and found no other genetic polymorphism or mutation except for apoE epsilon 4 and IE1 G alleles associated with AD. CONCLUSION: apoE epsilon 4 gene appears to be the strongest gene risk factor for late-onset AD and its apparent association between the IE1 G/G genotype and late onset AD is a consequence of the association between the epsilon 4 and IE1 G/G genotype. The PS-1/1 genotype is weakly associated with late-onset AD. PMID- 11775233 TI - Effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice. AB - OBJECTIVE: To study the effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice. METHODS: Human gastric cancer BGC-823 and MKN-45 cells were inoculated into spleen subcapsule of nude mice, respectively. The nude mice were subsequently administered with all-trans retinoic acid every other day. Food consuming and body weight of nude mice were measured weekly. Six weeks later, the nude mice were killed. Xenograft tumors in spleen and metastatic tumors in liver were pathologically examined. Microvessel density in the tumors was detected immunohistochemically, and serum carcinoembryonic antigen was measured by radioimmunoassay. RESULTS: After the nude mice were fed with all trans retinoic acid, the growth of splenic tumor and its liver metastasis were inhibited and the metastatic rates decreased by 50% (BGC-823) and 33.3% (MKN-45), respectively. The microvessel density in splenic and hepatic tumors reduced by 28.58% and 35.47% (BGC-823), 19.45% and 14.52% (MKN-45), respectively. The concentration of carcinoembryonic antigen decreased by 50.24% (BGC-823) and 48.10% (MKN-45). CONCLUSION: All-trans retinoic acid may effectively inhibit the growth of xenograft tumor in spleen and its metastasis to liver in nude mice, which can be corroborated by the decrease of carcinoembryonic antigen and microvessel density. PMID- 11775234 TI - Molecular cloning, sequencing and expression of obese gene in the Chinese. AB - OBJECTIVE: To construct the human obese (ob) cDNA clone in the Chinese, and analyze the expression of the ob gene in adipose tissue of obese, non-obese subjects and nooinsulin-dependent diabetes mellitus (NIDDM) Chinese patients. METHODS: A ob cDNA clone was isolated by reverse transcription polymerase chain reaction (RT-PCR). Four groups of Chinese subjects participated in the study: 1) 12 obese subjects [body mass index (BMI): 28.5 +/- 2.3 kg/m2]; 2) 11 non-obese subjects (BMI: 21.0 +/- 1.5 kg/m2); 3) 8 obese NIDDM patients (BMI: 27.0 +/- 1.4 kg/m2); 4) 11 non-obese NIDDM patients (BMI: 21.2 +/- 1.4 kg/m2). The expression of ob gene mRNA in abdominal subcutaneous adipose tissue was examined using RNA dot blot hybridization with a digoxigenin-labeled human ob cDNA probe. The hybridized signals were quantitated by densitometry. RESULTS: A full human ob cDNA fragment which included a glutamine codon at +49 was obtained. A base substitution (A to G) in the coding region at position 287 was found, resulting in a glutamine being replaced by an arginine. Expression of the ob gene was significantly higher in Chinese obese subjects compared to non-obese ones (P < 0.05), and positively correlated with the BMI. No significant difference in the amount of ob mRNA was detected between non-diabetic and diabetic groups at the same BMI level. CONCLUSIONS: We constructed a full length human ob cDNA clone. The expression of the ob gene was significantly higher in Chinese obese subjects than in non-obese ones. The metabolic and hormonal changes associated with NIDDM are not the main factors regulating the expression of the ob gene. PMID- 11775235 TI - Role of p38 protein kinase in heat-induced Raw cells apoptosis. AB - OBJECTIVE: To elucidate the role of p38 in heat-induced apoptosis in the monocytic cell line Raw264.7. METHODS: Apoptosis was detected using flow cytometric analysis, DNA electrophoresis, Westero blot and a protein kinase assay. RESULTS: A marked increased in p38 activity was detected 15 min after heating and reached maximal activity 30 min post stimulation, then returned to the pre-stimulated level 2 h later. The percentage of apoptotic cells was obviously increased 3 h after heating. Stimulation of p38 preceded the induction of apoptosis, and the p38 specific inhibitor, FHPI, can inhibit thermal injury induced cell apoptosis. CONCLUSIONS: p38 activation is required for heat-induced apoptosis in Raw264.7 cells, and stimulation of the p38 signaling pathway contributes to cell death. PMID- 11775236 TI - Oral mucosal conditions and some related factors in 140 Uygur centenarians. AB - OBJECTIVE: To investigate the condition of the oral mucosae in Xinjiang Uygur centenarians and explore some related factors. METHODS: The oral mucosae and mucosal exfoliative cells of 140 Xinjiang Uygur centenarians were examined. Saliva and blood were collected from some centenarians. Salivary immunoglobulins (IgA, IgM, IgG), complements (C3 and C4), nitrous oxide (NO), 10 trace elements, serum sex hormones, thyroid hormones and osteocalcin (OST) were analysed using immunoglobulin, complement and NO kits, an ionochromatophotometer, and the kits for sex hormones and thyroid hormones, and fluorescence enzyme-linked immunosorbent assay, respectively. RESULTS: Most centenarians (64.29%) had normal labial, buccal, palatal and gingival mucosae. The abnormal changes in mucosae were mainly vascular nevus patches and senile plaques. Their mucosal exfoliative cells showed similar characteristics to those in elderly Han. The centenarians who had normal mucosae had higher level of the trace element molybdenum (Mo) in their saliva than who had abnormal mucosae (P < 0.01). CONCLUSION: The oral mucosal condition of Uygur centenarians was generally good. The abnormal changes in oral mucosae of the centenarians were lesions not harmful to health and may be related to the lower level of Mo in their saliva. PMID- 11775237 TI - Temporary and permanent focal cerebral ischemia in the mouse: assessment of cerebral blood flow, brain damage and blood-brain barrier permeability. AB - OBJECTIVE: To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model. METHODS: CD-1 mice (n = 126) had permanent middle cerebral artery occlusion for 24 h, or temporary occlusion for either one hour followed by 23 h of reperfusion or 2 h of occlusion with 22 h of reperfusion. The middle cerebral artery was occluded by insertion of a suture through the internal carotid artery. Reperfusion was established by suture withdrawal. The degree of occlusion and the extent of reperfusion were determined using laser Doppler. Infarct volume was measured with 2, 3, 5-triphenyl tetrazolium chloride staining, and the blood-brain barrier disruption was demonstrated using albumin immunohistochemistry. RESULTS: Blood flow decreased to 14%-19% of baseline in both the permanent and temporary occlusion groups and was restored to 51%-75% of baseline after reperfusion. The infarct volume was smaller in the 1 h/23 h temporary occlusion group (P < 0.05) than in either the 24 h permanent occlusion group or the 2 h/22 h temporary occlusion group. Blood-brain barrier disruption was also smaller in the 1 h/23 h temporary occlusion group than in either the 24 h permanent occlusion or the 2 h/22 h temporary occlusion group (P < 0.05). CONCLUSION: Permanent or temporary middle cerebral artery occlusion causes reproducible brain injury in the mouse. Blood-brain barrier disruption and infarct volume remain important markers of focal cerebral ischemia. PMID- 11775238 TI - Recombinant bovine basic fibroblast growth factor accelerates wound healing in patients with burns, donor sites and chronic dermal ulcers. AB - OBJECTIVE: To evaluate the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on accelerating healing of burn wounds, donor sites and chronic dermal ulcers in multicenters. METHODS: One thousand and twenty-four patients with burns, donor sites and chronic dermal ulcers were recruited for this prospective and multicenter clinical trial and another 641 patients with the similar wounds were used as controls. All patients were divided into three groups: burn group, donor site group, and chronic dermal ulcer group. In the burn group, 654 patients with superficial second-degree burns(superficial II degree) or deep second-degree burns(deep II degree) were treated topically with either recombinant bovine basic fibroblast growth factor (rbFGF plus vehicle, rbFGF 150 AU/cm2/day, 330 patients) or placebo (vehicle without rbFGF, 324 patients). In the donor site group, 509 patients were treated with rbFGF and 317 patients with placebo in a similar way as described elsewhere. In the chronic dermal ulcer group, 185 patients were treated with rbFGF and the controls were themselves. Photography, histological evaluation and clinical examination were used to evaluate the results of wound healing. RESULTS: All of superficial second-degree burns, deep second-degree burns and the donor sites treated with recombinant bovine basic fibroblast growth factor had an accelerated rate of granulation tissue formation and epidermal regeneration as compared with that in the controls. Superficial second-degree burns and deep second-degree burns treated with recombinant bovine basic fibroblast growth factor healed in 9.89 +/- 2.45 and 17.04 +/- 4.56 days, respectively, whereas the average healing time in those receiving placebo was 12.35 +/- 2.74 and 21.21 +/- 4.88 days. The donor sites treated with rbFGF or placebo healed in 10.68 +/- 4.55 and 14.74 +/- 6.46 days, respectively. All chronic dermal ulcers except 12 patients treated with rbFGF healed within 6 weeks. Histological evaluation of punch-biopsy specimens from the burn wounds, donor sites and chronic dermal ulcers seven days after treatment supported the impression of accelerated wound healing after rbFGF treatment. CONCLUSIONS: rbFGF is effective in shortening the wound healing time and improving the wound healing quality. Accelerating wound healing is of clinical benefit in reducing the length of hospitalization, costs and emotional burden of the patient. PMID- 11775239 TI - Polymorphisms of TAP, LMP and HLA-DM genes in the Chinese. AB - OBJECTIVE: To investigate the distribution of antigen-processing genes transporter associated with antigen processing (TAP), low molecular weight proteasome (LMP2) and HLA-DM in the Shanghai population and to explore the possible role of these genes in the genetic susceptibility to autoimmune diseases IgA nephropathy(IgAN) and multiple sclerosis(MS). METHODS: Eighty normal Shanghai Chinese, 60 patients with IgAN and 21 patients with MS were randomly selected and genotyped for antigen-processing genes (TAP1, TAP2, LMP2, HLA-DMA and -DMB) using polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Two-locus linkage disequilibrium analysis was performed. RESULTS: Four TAP1, 6 TAP2, 2 LMP2, 3 DMA and 4 DMB alleles were observed. Statistically significant associations were found between TAP1B-TAP2A, TAP1B-LMP2H and TAP2D-HLA-DMA* 0101 (Pc < 0.01). There was no association between antigen-processing genes and either IgAN or MS. CONCLUSION: The polymorphisms of antigen-processing genes in this Shanghai population are similar to those observed in the other ethnic populations. No association was found between IgAN or MS and any antigen processing genes tested in Shanghai population. PMID- 11775240 TI - Primary carnitine deficiency in the Chinese. PMID- 11775241 TI - Moraxella catarrhalis meningitis: a case report. PMID- 11775242 TI - Wound healing research in the new century. PMID- 11775243 TI - Gene mutation in patients with primary open-angle glaucoma in a pedigree in China. AB - OBJECTIVE: To investigate the genetic basis of the pathogenesis of a Guangzhou (GZ.1) pedigree with primary open-angle glaucoma (POAG). METHODS: DNA fragments of the trabecular meshwork inducible glucocorticoid response protein (TIGR) gene from 4 typical POAG patients and 2 normal subjects were amplified by polymerase chain reaction (PCR). The amplified PCR fragment was cloned into a pT-Adv vector, and direct sequencing was carried out on an ABI-373 automated DNA sequencer using dyeterminator chemistry to detect the mutation. RESULTS: The TIGR gene mutation was identified in the selected subjects of this pedigree. This mutation is a "C to-T" transition at position 370, different from that of western countries and equivalent to the position change found in Japanese patients with familial POAG. No mutation was found in the TIGR gene fragment in 2 normal subjects of the pedigree. CONCLUSIONS: These preliminary results provide insights into the pathogenesis of POAG by the TIGR gene mutation, and into the underlying action of the different mutations in oriental and western peoples. PMID- 11775244 TI - Effect of 8-bromo-cyclic AMP on neuron specific enolase, heat shock protein, nitric oxide, nitric oxide synthase and nitric oxide synthase mRNA in human retinoblastoma HXO-Rb44 cells and cell differentiation. AB - OBJECTIVE: To study the effect of 8-bromo-cyclic AMP (8-Br-cAMP) on nitric oxide synthase (NOS) mRNA, NOS and nitric oxide (NO) product, heat shock protein (hsp) 70 and neuron specific enolase (NSE) in human retinoblastoma HXO-Rb44 cells and the effect related to cell differentiation. METHODS: Cultured human retinoblastoma HXO-Rb44 cells were divided into two aliquots. One was cultured with 2 x 10(-5) mol/L of 8-Br-cAMP for 24 hours as the experiment group; the other was treated with no 8-Br-cAMP as the control group. The cell suspensions in concentration of 1 x 10(7)/ml in both groups were dropped onto the nitrocellulose membrane (NCM). The NOS mRNA was detected with the biotin-labeled NOS cDNA probe by RNA dot blot. The NOS activity was detected by protein dot blot. The immunoreactivity (IR) of hsp70 and NSE was detected by protein dot blot. The NO was detected by nitrate reductase method. NCM specimens were analyzed by a TLC scanner for detection of the dot blot signal intensity. RESULTS: The signals of NOS mRNA, NOS activity, hsp70-IR, NSE-IR, and NO content in the experiment group were higher than those in the control group (P < 0.05-0.01). CONCLUSIONS: 8-Br cAMP could increase NO product and the expression of NOS mRNA, NOS, NSE and hsp70. The results indicate that 8-Br-cAMP could facilitate synthesis of NO in the neuroblastoma HXO-Rb44 cells, which could have tendency toward neuron development, suggesting that the increased hsp70, NO and NOS may involve cell differentiation of the retinoblastoma HXO-Rb44. PMID- 11775245 TI - Bilateral papilloedema associated with lumbo-sacral intraspinal tumor. AB - OBJECTIVE: To study the possible mechanism of bilateral papilloedema associated with intraspinal tumor at the lumbo-sacral level. METHODS: Three cases were reported. Detailed clinical history was evaluated. Patients were followed up for 2, 3 and 5 months after resection of the tumor. Related literature was reviewed. RESULTS: Papilloedema was soon resolved and the level of protein in the cerebrospinal fluid (CSF) decreased significantly after resection of tumor. These indicated a close relationship between papilloedema, CSF protein and intraspinal tumor. CONCLUSION: This is the first report of papilloedema associated with a lumbo-sacral intraspinal tumor in Chinese literature. The high level of protein in CSF may be the cause of both papilloedema and increased intracranial pressure. In patients with bilateral papilloedema, if no intracranial cause could be found, lumbo-sacral intraspinal tumor should be considered. PMID- 11775246 TI - Pulmonary function changes following surgical correction for pectus excavatum. AB - OBJECTIVE: To assess whether and to what extent pulmonary function returns to normal after surgical correction for pectus excavatum. METHODS: Twenty-seven patients who could be examined in person at the outpatient department of our hospital were included in this study. Of these patients, 24 were boys and 3 were girls, with age ranging from 3 to 16 years (mean: 8.67 years). The mean age at surgery was 4 years and mean years at follow-up was 6.8. Pulmonary function measurements included inspiratory vital capacity (IVC), total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), RV/TLC ratio, maximal voluntary ventilation (MVV), forced ventilatory capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid-expiratory flow (MMEF), maximal expiratory flow at 75% vital capacity (V75), maximal expiratory flow at 50% vital capacity (V50), maximal expiratory flow at 25% vital capacity (V25) and breathing reserve ratio (BR). RESULTS: TLC, FRC, MVV, MMEF, V75 and V50 were not different from normal values. IVC, FVC, FEV1 and V25 were significantly decreased compared with normal values. RV and RV/TLC were high in 87.5% cases. CONCLUSIONS: Preoperative symptoms improved substantially after operation. Little airway obstruction was observed postoperatively, suggesting that patients with pectus excavatum should have surgery as early in life as possible, preferably by age 3. PMID- 11775247 TI - Changes in airway responsiveness and relative factors in asthma with remission at puberty. AB - OBJECTIVE: To elucidate the airway responsiveness and its relative factors in asthma with natural remission at puberty. METHOD: The airway responsiveness was evaluated by provocation of methacholine (PC20). Blood sIL-2R, IL-4 and IFN-gamma values in the cultural supernatant of mononuclear cells, eosinophil count, basophil count and basophil releasability were detected in 18 asthmatic cases with remission at puberty (group I), in 20 asthmatics without remission at puberty (group II), and in 30 healthy controls (group III). RESULT: The mean value of PC20 in group I was significantly lower than that in group III (P < 0.01), but still higher than that in group II (P < 0.01). The blood sIL-2R, and eosinophil counts dropped almost to those of group III, significantly lower than those of group II. IL-4 in the culture supernatant of mononuclear cells was similar to group III, but significantly lower than that in group II. However IFN gamma was also similar to group III, significantly higher than that of group II. The basophil count and positive rate of human basophil degranulation test stimulated by mannitol with hyper-osmolarity were still abnormal, significantly higher than those of group III, and the basophil level was significantly related to the airway responsiveness. CONCLUSION: The asthmatics with remission at puberty have a certain degree of airway hyper-responsiveness that is related to the abnormality of basophil. PMID- 11775248 TI - Establishment and pathological study of models of chronic obstructive pulmonary disease by SO2 inhalation method. AB - OBJECTIVE: To establish rat models of chronic obstructive pulmonary disease (COPD) and study the pathological characteristics of airflow obstruction. METHOD: SO2 inhalation method was used to establish rat models. After exposure to SO2 for 7 weeks, peak expiratory flow (PEF), peak inspiratory flow (PIF), intratracheal pressure (IP) and IP slope in rat were measured by Maclab data recording and analysis system. Experimental rats with PEF less than 80% of the mean of the normal rats were classified as airflow obstructed, while those with PEF greater than 80% of mean of normal rats were non-obstructed. Pathological changes in airway and lung tissue were compared between these two groups. RESULT: In experimental animals, PEF was significantly decreased (P < 0.005) and IP slope increased (P < 0.001) as compared with normal rats. Epithelial damage, goblet cell hyperplasia and inflammatory cell infiltration in cartilaginous bronchi were more remarkable in experimental rats with airflow obstruction than those without airflow obstruction (P < 0.001, < 0.01, < 0.001, respectively). Furthermore, pathological changes in airway lumen, epithelium and airway wall in membranous and respiratory bronchioles were more marked in experimental rats with airflow obstruction than those without airflow obstruction (P < 0.001 or P < 0.05). There was a negative correlation between PEF values and epithelial hyperplasia, goblet cell hyperplasia, inflammatory cell infiltration, smooth muscle hyperplasia and mucous plug in membranous and respiratory bronchioles (P < 0.001 or P < 0.05). CONCLUSION: SO2 inhalation may cause chronic bronchitis with airflow obstruction, i.e. COPD in rats. COPD was induced in 64% (16 of 25) of the experimental group rats. PMID- 11775249 TI - Effects of endothelin B receptor antagonists, BQ788 and ET-1(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs. AB - OBJECTIVE: To explore the role of endothelin (ET) in the pathogenesis of exercise induced asthma (EIA), we investigated the effects of ETB receptor antagonists, ET 1(11-21) fragment and N-cis-2, 6-dimethylpiperidinocardonyl-L-gamma-methylleucyl D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ788) on bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs. METHODS: Eighteen pathogen-free Hartley guinea pigs were randomly divided into three groups. A: normal saline (NS) inhalation control group (n = 6), B: BQ788 group (n = 6), and C: ET-1(11-21) fragment group (n = 6). Guinea pigs were anesthetized with pentobarbital sodium. After measuring the basal value of lung resistance (RL) and dynamic compliance of the respiratory system (Cdyn), NS (0.96 ml), BQ788 (9 nmol) and ET-1(11-21) fragment (9 nmol) were inhaled. A rodent respirator with a dry 5% CO(2)-95% O2 mixture at room temperature provided mechanical ventilation (VT8 ml/animal, 100 breaths/min) for 5 min. RL and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge. RESULTS: In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of the guinea pigs from BQ788 group and ET-1(11-21) fragment group did not change significantly. CONCLUSION: It was demonstrated that selective ETB receptor antagonists, ET-1(11-21) fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors. It was suggested that ET receptor antagonists, especially ETB receptor antagonist, might be beneficial in preventing EIA. PMID- 11775250 TI - Stenting versus non-stenting after revascularization of chronic total coronary artery occlusion: short- and long-term clinical and angiographic results. AB - OBJECTIVE: To investigate the short- and long-term clinician and angiographic outcome of stenting or angioplasty for chronic total coronary artery occlusion. METHODS: A total of 95 patients with successful percutaneous transluminal coronary angioplasty (PTCA) for total occlusion coronary artery were identified out of 358 patients undergoing PTCA for chronic total occlusion. Patients were classified into two groups: Group A had selective stenting after successful PTCA and Group B only had PTCA. Clinical cardiac events including acute myocardial infarction (AMI) angina, death, repeat revascularization and angiographic variables were followed and analyzed. RESULTS: A total of 85 of 95 patients (89%) completed clinical and angiographic follow-up. In group A (n = 42), 1 patient experienced an AMI while in group B, 2 patients experienced AMI and 1 died. In group A, the restenosis rate was 29%, reocclusion rate was 12% and recanularization rate was 19%, as compared to 58%, 22% and 45% respectively in group B (P < 0.001, P < 0.05 and P < 0.001, respectively). CONCLUSIONS: Selective stent improves short- and long-term clinical and angiographic outcomes and is recommended in cases of chronic total occlusion independent of the primary PTCA results. PMID- 11775251 TI - An experimental study of endovascular brachytherapy using liquid 32P filled balloon catheter. AB - OBJECTIVE: To observe the effect of endovascular brachytherapy on the prevention of restenosis after interveneional therapy and to investigate its possible mechanisms. METHODS: In the balloon-injuried rabbit model, pathological sections of iliac arteries were observed and the changes of vascular histomorphology were estimated by computer analysis of photomicrograms. Using immunohistochemical techniques, proliferating cell nuclear antigen (PCNA) was quantified to assess the proliferation of vascular smooth muscle cells. RESULTS: After rabbit iliac arteries were injured by balloon overstretch angioplasty, neointima were shown to be less proliferative in the irradiated group than in the control group, from PCNA scores. The formation of neointima was suppressed with the external elastic laminar area increasing and without the luminal area decreasing in the irradiation group. CONCLUSION: Endovascular brachytherapy using a liquid 32P filled balloon catheter system could prevent restenosis possibly by inhibiting the formation of neointima and improving positive vascular remodeling. PMID- 11775252 TI - Expression of the human multidrug resistance gene mdr1 in leukemic cells and its application in studying P-glycoprotein antagonists. AB - OBJECTIVE: To investigate the retrovirus-mediated transfer and expression of multidrug resistance gene (mdr1) in hematopoietic cells and to develop a model for studying the possible reversal of the MDR-mediated phenotype. METHODS: A retroviral vector HaMDR expressing the human mdr1 gene was packaged by PA317 cells with a titer of up to 8.5 x 10(5) CFU/ml. K562 leukemia cells were infected with MDR retrovirus, and transfectant K562/MDR cells were generated. The integration and expression of the exogenous mdr1 gene in K562/MDR cells were determined by polymerase chain reaction and flow cytometry. The reversal ability of P-glycoprotein (P-gp) antagonists was analyzed by in vitro drug sensitivity, accumulation and efflux of rhodamine 123 (Rh123) in this model. RESULTS: Transduction with amphotropic MDR retrovirus resulted in integration and expression of the mdr1 gene in the resistant cells, where an aberrant splicing transcript of the mdr1 gene was found. The K562/MDR cells displayed a classic MDR phenotype with a 41-78 fold resistance to vincristine and colchicine in comparison with parental K562 cells. The drug sensitivity of K562/MDR cells to vincristine can be completely restored by cyclosporin A (CsA, 2 mg/L) and Cremophor EL (CRE 132 mg/L), either individually or in combination (P < 0.05). CsA (3 mg/L) can block the efflux pump function of P-gp shown by the significantly increased accumulation and efflux reduction of Rh123 in K562/MDR cells. CONCLUSIONS: Retroviral vector HaMDR allows transfection with high-level expression of the mdr1 gene in human myeloid progenitor cells K562. The transfected K562/MDR provides a simple, sensitive model for developing antagonists of P-gp and studying their mechanism of action. PMID- 11775253 TI - Cytokine expression of T cells in chronic myeloid leukemia. AB - OBJECTIVE: To evaluate the function of T cells in chronic myeloid leukemia (CML). METHODS: Interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-3 (IL 3), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and granulocyte macrophage-colony stimulating factor (GM-CSF) gene expressions were investigated by reverse transcription polymerase chain reaction (RT-PCR) assay in fluorescence active cell sorter (FACS) sorted peripheral blood CD2+/CD56-T cells from 12 CML patients, 10 meylodysplastic syndrome (MDS) patients and 7 normal individuals. RESULTS: TNF alpha mRNA was transcribed in T cells from all of the CML, MDS and normal individuals. IL-1 beta mRNA was transcribed in T cells from 10 CML, 9 MDS and 6 normal individuals. Low levels of IL-2 and IL-4 mRNA were detected in 5 CML patients. IL-3, IL-6 and GM-CSF mRNA were undetectable in all samples. CONCLUSION: IL-4 and IL-2 were expressed abnormally in T cells of CML. PMID- 11775254 TI - Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment. AB - OBJECTIVE: To study in vivo effect of all-trans-retinoic acid (ATRA) or arsenic trioxide (As2O3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients. METHODS: The plasma variables were measured by ELISA or chromogenic study. The TF transcription was assessed using reverse transcription-polymerase chain reaction technique (RT-PCR). RESULTS: The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As2O3 therapy. The plasma level of platelet alpha-granular membrane protein-140, soluble fibrinomonomer complex, thrombomodulin, tissue plasminogen activator and D-dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, alpha 2-plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group. CONCLUSIONS: There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As2O3 therapy down-regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment. PMID- 11775255 TI - The synergistic enhancement of pathology in intermittently cooled nerve. AB - OBJECTIVE: To explore how non-freezing cold nerve injury (NFCNI) is affected by fluctuating ambient temperatures. METHODS: The sciatic nerves of Wistar rats were exposed to either intermittent cooling and rewarming or continuous cooling. The pathology was assessed neurophysiologically and morphologically. RESULTS: More severe injury was observed when nerve was intermittently cooled, despite an identical duration and degree of cooling. CONCLUSION: The observed pathology is a result of repeated reperfusion injury to nerves that are cooled intermittently. PMID- 11775256 TI - Testicular sperm extraction and intracytoplasmic sperm injection in non obstructive azoospermia. AB - OBJECTIVE: To report the experience in sperm extraction from testicular biopsies (TESE) performed from March 1996 to July 1998 in men with non-obstructive azoospermia (NOA). METHODS: Comparisons of age, volume of both testes, serum FSH and testosterone in men, and histology of testicular samples in the first cycles between cycles with spermatozoa found and those without spermatozoa found were performed. Comparisons of fertilization, cleavage and pregnancy rates between cycles with spermatozoa injected and those with spermatids injected were performed. RESULTS: Spermatozoa were found in only 12 out of 26 first TESE cycles (46.2%) and other cycles had spermatids (round cells) only. Age of men, history of mumps orchitis/oligozoospermia, volume of both testes and serum FSH/testosterone levels in men were not significantly different between cycles with and without spermatozoa. The fertilization rate was significantly higher in cycles with spermatozoa injected than those with round cell injections (63.3% vs 23.2%, P < 0.0001, Chi-squared test). The pregnancy rate was 14.3% per cycle when spermatozoa were injected. CONCLUSIONS: TESE followed by intracytoplasmic sperm injection (ICSI) is an effective treatment in patients with NOA. Less than half of the patients undergoing TESE had spermatozoa recovered. Age of men, volume of both testes and serum FSH/testosterone levels in men were not useful in predicting successful recovery. Compared to using ejaculated and epididymal spermatozoa, fertilization and pregnancy rates were achieved when testicular spermatozoa were used for ICSI. PMID- 11775257 TI - Pulmonary embolism associated with nephrotic syndrome in children: a preliminary report of 8 cases. AB - OBJECTIVE: To investigate the incidence, clinical features of pulmonary embolism (PE) secondary to nephrotic syndrome(NS) in Chinese children. METHODS: Pulmonary perfusion imaging (PPI) and chest radiography was performed on 20 NS patients with elevated plasma D-dimer. The patients with PE were given anticoagulative therapy with heparin and persantine. RESULTS: Among 20 NS patients, eight cases, aged from 5 to 12 years, 6 boys and 2 girls, were found to have PE. Of them 5 were primary NS and 3 were secondary NS. PPI showed an involvement of 1 pulmonary segment in 3 cases, of 2 pulmonary segments in 2, of 3 pulmonary segments in 2, and of 6 pulmonary segments in 1. Most patients did not present clinical signs and symptoms. Two weeks after the administration of intravenous heparin for anticoagulative therapy, 6 out of 8 cases showed a recovery or an improvement. CONCLUSION: The results of this study suggest that PE be not a rare complication in NS children. Most patients had no obvious clinical manifestation and their prognose was favorable if diagnosed and treated in time. PMID- 11775258 TI - Brain MRI of hippocampal volumetry in patients with refractory temporal lobe epilepsy. AB - OBJECTIVE: To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy. METHODS: Eighty-four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry. A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0.91. RESULTS: Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient. Other MRI abnormalities were detected in 18 patients with or without coexisting HA. CONCLUSIONS: Hippocampal sclerosis can be detected presurgically in many patients by brain MRI. Additional abnormalities not detected by brain CT can also be demonstrated. PMID- 11775259 TI - CT via percutaneous splenoportography: experiment and application. AB - OBJECTIVE: To introduce computed tomography via percutaneous splenoportography (CTSP), a new method for determining hepatic diseases. METHODS: Ten hybrid dogs and 31 patients with primary hepatic cancer (PHC) were included in the study. Each dog was examined by CT, computed tomography via arterial portography (CTAP), and CTSP to compare the enhanced density of the liver. The 31 patients were examined by CTSP and the appearance of PHC was compared with their pathological results to evaluate the diagnostic significance of CTSP. RESULTS: The animal experiment showed that both CTAP and CTSP could obviously enhance the density of the liver (P < 0.01), but no significant difference was observed in the enhanced densities between the two methods (P > 0.05). On the CTSP images of the 31 patients, the density of the livers was increased to 168-192 Hu, whereas the density of the cancers was as low as that on the images of CT scans (< 58 Hu). The CTSP findings were consistent with the surgical ones from space occupying lesions. The diagnostic value of CTSP was obviously superior to that of general enhanced CT. However, it was difficult for CTSP to show nodules less than 1 cm in size located on the surface of the liver or the hepatic portal zone. CONCLUSIONS: Like CTAP, CTSP is also a sensitive method for showing occupant in the liver. But the equipments and the procedures are simpler for CTSP than for CTAP. CTSP is an alternative procedure in clinical practice. PMID- 11775260 TI - Magnetic susceptibility of Dy-DTPA-BMA to reperfused myocardial infarction in an excised dog heart model: evidence of viable myocardium. AB - OBJECTIVE: To assess the effects of Dy-DTPA-BMA (sprodiamide) on ex-vivo MR imaging of reperfused acute myocardial infarction. METHODS: Eighteen dogs were subjected to 2-hour coronary artery occlusion followed by 24-hour reperfusion. Dysprosium-chelate (Dy-DTPA-BMA) was injected into 16 dogs. Twenty minutes before their sacrifice. Two dogs did not receive the contrast medium and were used as controls. Excised hearts were imaged on T2-weighted spin-echo sequence (T2W SE) and T2*-weighted gradient recalled echo sequence (T2*W GRE), then sectioned and double-perfused for planimetric comparison. RESULTS: Dy-DTPA-BMA induced myocardial signal loss was detected on T2W SE and on T2*W GRE images. The signal loss was observed at the subendocardial location of the myocardial wall inducing an apparent enlargement of the left ventricle cavity and a thinning appearance of the anterior myocardial wall. CONCLUSIONS: Myocyte necrosis diminishes the potency of dysprosium to cause MR imaging signal intensity loss in reperfused myocardial infarction. Pre-infarcted myocardium with potentially reversible viability may be responsible for the effect of the contrast medium. PMID- 11775261 TI - Anti-fecundity immunity in mice immunized with anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum. AB - OBJECTIVE: To observe the effects of anti-fecundity and anti-embryonation immunity of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum on female adult worm. METHODS: The active immunization of C57BL/6 mice was conducted by means of three intraperitoneal injections of NP30. The control group was injected with SP2/0 ascites intraperitoneally. RESULTS: On the twenty-seventh day after challenge infection, the number of eggs in the liver tissue and in uterus of the group immunized with NP30 decreased by 30.91% and by 38.55%, respectively. On the thirty-ninth day after the challenge infection, the number of mature eggs in the liver tissue of the group immunized with NP30 decreased by 66.63% and the number of dead eggs increased by 60.66%. CONCLUSIONS: NP30, with which mice were actively immunized, possesses double effects of anti-fecundity and anti embryonation immunity on female adult worm of Schistosoma japonicum, therefore it can be used as a promising candidate of anti-pathologic vaccine molecule against Schistosomiasis japonica. PMID- 11775262 TI - Vasoactive effects of adrenotensin and its interactions with adrenomedullin. AB - OBJECTIVE: To investigate the vasoactive effects of adrenotensin and the interactions between adrenotensin and adrenomedullin (ADM). METHODS: Isolated rat aortic tension, rat mean arterial pressure and 3H-TdR incorporation of rat vascular smooth muscle cells were measured. Isolated rat aortas were incubated in K-H solution containing adrenomedullin or adrenotensin. The released adrenotensin or adrenomedullin (in incubation medium) from rat aortas was measured by radioimmunoassay. RESULTS: 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin augmented rat aortic tension in a dose-dependent manner (P < 0.01). An intravenous bolus injection of adrenotensin (2.5 nmol/kg, i.v.) increased the mean arterial pressure by 28% in anesthetized rats (P < 0.01). 1 x 10(-7) mol/L adrenotensin increased 3H-TdR incorporation in cultured rat vascular smooth muscle cells by 55% (P < 0.01). Adrenomedullin inhibited these activities of adrenotensin to different extents. 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin decreased adrenomedullin release rates by 19%, 35% and 46%, respectively (P < 0.05 or P < 0.01) and 1 x 10(-8) mol/L adrenomedullin also inhibited adrenotensin release by 45% from rat aorta (P < 0.01). CONCLUSION: Adrenotensin is a novel peptide that elicits the activities of vasoconstriction, pressor effects and induces the proliferation of vascular smooth muscle cells. There is antagonism in vascular activities and reciprocal inhibition in the release between adrenotensin and adrenomedullin. These interactions are manifestations of intramolecular regulation of proadrenomedullin (Pro-ADM). PMID- 11775264 TI - Immune response to plasmid DNA encoding HPV16-L1 protein. AB - OBJECTIVE: To test the immunogenicity of recombinant plasmid DNA containing human papillomavirus type 16-L1 (HPV16-L1) coding sequence of mice. METHODS: The HPV16 L1 encoding sequence was generated by polymerase chain reaction (PCR), and inserted into TA cloning vector PCR II, then cloned in the eukaryotic expression vector pcDNA3.1 with CMV promoter. The recombinant plasmid DNA pcDNA-L1 was transferred into Cos-7 cells and used to immunize BALB/c mice via muscular injection. The expression of HPV16-L1 in transferred cells was identified by immunospot and immunocytochemistry, which tested specific anti-HPV16-L1 antibody in the serum of immunized mice. RESULTS: Using the immunospot technique, we found L1 protein expression in pcDNA-L1 transferred cells. The immunocytochemistry studies demonstrated that the L1 protein was located in nuclei. In immunized mice, specific anti-HPV16-L1 antibodies could be detected by immunospot and immunocytochemistry 28 days after the first immunization and last at least 41 days. CONCLUSIONS: We constructed HPV16-L1 eukaryotic expressing plasmid whose DNA could induce immunohumoral response in mice. This observation will be helpful in designing HPV16 prophylactic vaccine. PMID- 11775263 TI - Expression of fibronectin receptor, integrin alpha 5 beta 1 of hepatic stellate cells in rat liver fibrosis. AB - OBJECTIVE: To investigate the role of fibronectin (FN) receptor alpha 5 beta 1 in liver fibrosis. METHODS: Northern blot analysis and immunohistochemical techniques were used to observe changes in the expression of FN and FN receptor alpha 5 beta 1 on hepatic stellate cells (HSCs) in vivo and in vitro of rat liver fibrosis induced by CCl4. RESULTS: (1) alpha 5 beta 1 was mainly detected in the endothelia and some of the desmin(DM) positive cells of the sinusoids in normal rat liver. The expression of alpha 5 beta 1 of DM positive cells detected by immunohistochemistry reached its peak at the 10th week of the experiment. The changes in FN expression were similar to that of alpha 5 beta 1. (2) The expression of FN, alpha 5 and beta 1 mRNAs in the experimental group was remarkably increased especially at the 6th week, compared to that of normal liver specimens. The expression of the three mRNAs of HSCs in vitro isolated from the experimental group (6 weeks) was higher than those from normal liver. (3) The expression of FN, alpha 5 and beta 1 mRNAs increased in normal rat HSCs after treatment with transforming growth factor-beta 1 (TGF-beta 1) for 2 hours. After 4 hours of treatment, the expression of the three mRNAs fell to levels similar to the control group. Immunocytochemistry revealed that the expression of alpha 5 beta 1 of HSCs reached its peak after 4 hours of treatment with TGF-beta 1 and dropped to normal 2 hours later. CONCLUSION: These data suggest that HSCs normally express FN receptor alpha 5 beta 1. The activation of HSCs during liver fibrogenesis leads to an increase of FN, alpha 5 and beta 1 mRNA expression. The expression of FN and alpha 5 beta 1 of HSCs in vitro is up-regulated by TFG-alpha 5 beta 1. The detection of gene transcription of FN and its receptor by Northern blot analysis suggests the activation and proliferation of HSCs and thereby provides a sensitive signal of liver fibrosis. PMID- 11775265 TI - Macrophage activation of lymphoma-bearing mice by liposome-mediated intraperitoneal IL-2 and IL-6 gene therapy. AB - OBJECTIVE: To investigate the antitumor mechanism of interleukin-2 (IL-2) and interleukin-6 (IL-6) gene therapy. METHODS: Liposome encapsulated IL-2 DNA and IL 6 DNA were intraperitoneally (i.p.) injected into mouse lymphoma cell line (EL-4) lymphoma-bearing mice. Macrophage function (M phi) from the mice was assessed. RESULTS: Cytotoxicity, major histocompatibility (MHC) II expression and IL-1 and TNF secretion of the macrophages all augmented after i.p. injection of liposome encapsulated IL-2 DNA or IL-6 DNA. More efficient activation of macrophages was observed in mice treated with liposome encapsulated IL-2 DNA than IL-6 DNA. IL-2 gene therapy combined with IL-6 gene therapy showed the maximal activation of macrophages in the lymphoma-bearing mice. CONCLUSION: IL-2 and IL-6 gene therapy can relieve the suppression of macrophages of the lymphoma-bearing mice, and efficiently activate the antitumor immune responses. PMID- 11775266 TI - Soluble cell adhesion molecules in patients with acute coronary syndrome. AB - OBJECTIVE: To observe the changes in serum soluble intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), E selectin and von Willebrand factor (vWf) in patients with acute coronary syndrome. METHODS: Serial venous blood samples were taken from 21 patients with acute myocardial infarction (AMI) before and 4, 8, 12, 24, 48 and 72 h after thrombolytic treatment or direct PTCA. One blood sample was drawn from 16 patients with unstable angina and 16 control subjects. Serum concentrations of ICAM-1, VCAM-1, E-selectin and vWf were determined using a double antibody sandwich enzyme-linked immunosorbent assay. RESULTS: Serum levels of ICAM-1, VCAM 1, E-selectin and vWf were higher in patients with acute coronary syndrome than in controls. Patients with AMI and successful reperfusion therapy had a significant reduction in the serum concentration of ICAM-1 and E-selectin at 24 and 48 h, VCAM-1 at 24 and 72 h and vWf at 12, 24, 48 and 72 h, but had peak in serum levels of ICAM-1 and E-selectin at 4 h. The number of diseased coronary arteries was not related to the levels of ICAM-1, VCAM-1 and E-selecin. CONCLUSION: The serum concentration of soluble cell adhesion molecules was elevated significantly in patients with acute coronary syndrome. Successful reperfusion therapy was associated with a reduction in the serum concentrations of soluble cell adhesion molecules in patients with AMI. PMID- 11775267 TI - Price survey. Gown prices head back up. PMID- 11775268 TI - Buying, selling used items can yield savings, income. PMID- 11775270 TI - Supply chain vulnerable in many ways. AB - The specter of terrorism has reached the materials management department, now that a supply room worker in a New York hospital has died from anthrax. At the same time, the tragedy of the Sept. 11 attacks has led hospitals and their vendors to realize that "partnership" is not just a trendy word for business association anymore; it is a strategy for survival. PMID- 11775271 TI - Simulator "patients" introduce students to new technology. PMID- 11775272 TI - A future without drills and fillings? PMID- 11775273 TI - Bill introduced to ban mercury-based fillings by 2007. PMID- 11775274 TI - Peer assistance programs help dentists battle substance abuse. PMID- 11775275 TI - Oral candidiasis most prevalent HIV oral manifestation. PMID- 11775276 TI - Herbal therapy and increased risk for surgery. PMID- 11775277 TI - Take this job and love it! PMID- 11775278 TI - Achieving total smile enhancement through tooth whitening and placement of a single anterior veneer restoration. PMID- 11775279 TI - Auto-cure GIC-composite co-cure technique. PMID- 11775280 TI - Nonsurgical endodontic re-treatment, Part 2. PMID- 11775281 TI - Regional and systemic causes of craniofacial pain: case reports. PMID- 11775282 TI - Achieving aesthetics with implant-supported all-ceramic crowns. PMID- 11775283 TI - Combining the single implant with a CAD/CAM restoration. PMID- 11775284 TI - Bipolar versus monopolar electrosurgery: clinical applications. PMID- 11775286 TI - Communicating value: how to get more out of cosmetic dentistry. PMID- 11775285 TI - The oral physician: how do we get from here to there? PMID- 11775287 TI - A day in the life of a dental office computer. PMID- 11775288 TI - Global situation of the HIV/AIDS pandemic, end 2001. Part I. PMID- 11775289 TI - Vaccines and biologicals. Part II. Recommendations from the Strategic Advisory Group of Experts. PMID- 11775290 TI - Perspectives. M+C heads back to the drawing board. PMID- 11775291 TI - Drawing from experience. AB - The journey through grief after exposure to a sudden traumatic death is a painful and personal experience for children. This requires therapeutic interventions that explore and facilitate the healing potential within each child. Drawings are an expressive method that can provide a conduit for identifying and understanding issues requiring therapeutic intervention and follow up. PMID- 11775292 TI - Identification and classification of postpartum psychiatric disorders. AB - 1. Postpartum depression has been used as a catchall phase for many postpartum emotional symptoms. Categorizing a number of diverse disorders under one title has resulted in an inability to identify who is most at risk for developing postpartum problems. 2. The postpartum period is a particularly vulnerable period for depression, despite the fact that it is perceived as a time of joy and emotional well-being. 3. By increasing awareness among all health care professionals who care for women during the period following childbirth, postpartum psychiatric disorders can be identified early and treated correctly. 4. Limiting postpartum psychiatric disorders to postpartum depression may result in limited or inappropriate treatment options. PMID- 11775293 TI - (Not) a Hallmark holiday. Experience of family caregivers of a relative with Alzheimer's disease. AB - 1. The holiday season may be an especially difficult time for families that have a relative with a dementia. 2. The three themes identified in interviews with family caregivers of a relative with Alzheimer's disease concerned becoming aware of the relative's symptoms, trying to have one last normal holiday, and deciding how to handle the holidays when the relative was in an assisted living facility. 3. Health care providers can help families by planning interventions to decrease stress during the holiday season. PMID- 11775294 TI - Professional support for family caregivers of people with serious and persistent mental illnesses. AB - 1. Professional support for family caregivers of people with serious and persistent mental illnesses is essential to ensuring the well-being of the caregivers and maximizing the functioning of the ill person. 2. Significant percentages of family caregivers had never received critical elements of instrumental and affective support from mental health care professionals. 3. The role of psychiatric nurses encompasses the responsibility to address these deficits, as well as multiple opportunities to do so. PMID- 11775295 TI - Need for knowledge of ethics. PMID- 11775297 TI - Patient education. PMID- 11775296 TI - On theories and evidence-based practice. PMID- 11775298 TI - Appropriate use of pilot studies. PMID- 11775299 TI - An international imperative for gender-sensitive theories in women's health. AB - PURPOSE: To propose gender-sensitive theories as a future direction for theoretical development of women's health. Few theories pertain to women's health and illness experiences, with gender issues embedded in social, cultural, and historical contexts. ORGANIZING CONSTRUCT: Significance, definition, and philosophical bases of gender-sensitive theories. FINDINGS: Six major components should be incorporated in the development of gender-sensitive theories: (a) gender as a major feature, (b) women's own words and experiences, (c) nature of women's experiences, (d) theorists' perspectives, (e) contexts, and (f) guidelines for actions. CONCLUSIONS: We believe that the development of gender sensitive theories in nursing could enable researchers to transcend androcentric and ethnocentric views on women's health, decrease gender inequity in health care, enhance women's well being, and ultimately contribute to knowledge development in nursing. PMID- 11775300 TI - Physical activity research in nursing. AB - PURPOSE: To present exemplars of physical activity research in nursing, illustrate the importance of physical activity research across the lifespan, and recommend directions for theory development and research. METHODS: Studies of physical activity and exercise currently being conducted by nurse investigators were reported and critiqued by attendees of the Midwest Nursing Research Society 2000 Preconference session entitled "Promoting Physical Activity Among Diverse Groups Across the Health Continuum." Physical activity and exercise literature during the past decade was reviewed. Databases searched included Medline, CINAHL, Wilson, and ERIC. FINDINGS: Investigators have emphasized the need to evaluate the effects of theory-based physical activity interventions designed to alter key correlates of physical activity identified through descriptive research. CONCLUSIONS: Regular physical activity is necessary for health promotion and disease prevention for all populations. Continued research in this important area of health behavior is critical to identify the most effective interventions to increase physical activity among diverse populations. PMID- 11775301 TI - Promoting responsiveness between mothers with depressive symptoms and their infants. AB - PURPOSE: To test the efficacy of an interactive coaching intervention to promote responsiveness between mothers experiencing postpartum depressive symptoms (PPDS) and their infants. DESIGN: An experimental design with 117 postpartum women in the Northeastern United States. METHODS: Participants were randomly assigned either to the treatment or control group. Both groups had home visits at 4-8 weeks, 10-14 weeks, and 14-18 weeks postpartum and mother-infant interaction was videotaped and coded for responsiveness. The treatment group also received a coached behavioral intervention designed to promote maternal-infant responsiveness. Measures included the Edinburgh Postnatal Depression Scale, the Beck Depression Inventory-II, and the Dyadic Mutuality Code. FINDINGS: The hypothesis, that the treatment group would show significantly higher maternal infant responsiveness after the intervention, was supported. No effect of the intervention on depression scores was found. A significant increase in responsiveness and a significant decrease in depression scores occurred over time for both treatment and control groups. No interaction between group and time was detected. CONCLUSIONS: The study showed that a coaching strategy had a positive effect on maternal-infant interaction in this sample. Future research is needed to test coaching interventions in conjunction with other strategies targeted to promote maternal-infant responsiveness and to reduce PPDS. PMID- 11775302 TI - Cultural practices and social support of pregnant women in a northern New Mexico community. AB - PURPOSE: To describe the experience of social support in Hispanic families during pregnancy. DESIGN: Ethnographic investigation, conducted from November 1995 to November 1997 in Rio Arriba County of northern New Mexico. METHODS: Seventy-two transcribed verbatim interviews with Hispanic mothers, family members, and health care providers, along with fieldnotes from participant observation, historical data of the region, and area demographics comprised the data for qualitative analysis. FINDINGS: Pregnancy outcomes were positive because of a socialization process that helped pregnant Hispanic women and family members adapt and change to support the pregnancy. This mutual shaping helped reinforce the family structure, integrate cultural beliefs, define roles for both mother and family members, define the nature of mother-child and family-child relationships, and facilitate a positive process through a supportive orientation. CONCLUSIONS: Findings showed the dynamics and context of relationships that constituted social support conducive to healthy birth outcomes in Hispanic families of northern New Mexico. The findings were enlightening concerning the pregnancy process, role adaptation, integration of health care beliefs, and provided ideas for intervention models that might benefit pregnant women, infants, family members, community members, and health care professionals. PMID- 11775303 TI - The theory of planned behavior and postpartum smoking relapse. AB - PURPOSE: To explore the applicability of Ajzen's theory of planned behavior to postpartum smoking relapse. ORGANIZING FRAMEWORK: The theory of planned behavior is proposed as an appropriate framework for the study of postpartum smoking relapse. METHODS: The literature on smoking cessation, postnatal smoking, and the theory of planned behavior were reviewed. References included electronic database and manual search results. CONCLUSIONS: The theory of planned behavior provides a framework for explaining, predicting, and influencing human behaviors based on modifiable factors of attitude, subjective norm, and perceived behavioral control. The inclusion of instrument development guidelines significantly strengthens the usefulness of the framework. A theoretically based understanding of postpartum smoking relapses can guide and strengthen appropriate interventions directed toward significantly reducing postpartum smoking, thereby increasing the number of women who are able to remain smoke-free for life. PMID- 11775304 TI - Infant exposure to environmental tobacco smoke. AB - PURPOSE: To identify infant health outcomes that have been empirically associated with environmental tobacco smoke (ETS) exposure in current international research literature. METHODS: Reports of infant ETS exposure, obtained using computerized searches of CINAHL and Medline databases, were reviewed. Studies of infant health outcomes published between 1995 and 2000 were included if they met specific criteria including the selection of infant ETS exposure as a major study variable. FINDINGS: The 10 studies in this integrative review of the literature were conducted in a variety of international health care settings. Positive associations were found between infant ETS exposure and gastroesophageal reflux, colic, sudden infant death syndrome, lower respiratory tract infections, and other infant morbidities. Parental self-reports were the predominant measures of ETS exposure. Maternal smoking was reported as a significant predictor of infant health outcomes. CONCLUSIONS: Nurses who care for mother-infant dyads in the first year of life are needed to support the development of a "gold standard" for the measurement of ETS exposure that is reliable, valid, and economical. In the interim, the global nursing community may use the findings of these current studies as justification for directing infant health care resources to smoking cessation interventions specifically tailored to meet the needs of mothers who smoke. PMID- 11775305 TI - Evaluation of an instrument for assessing behavioral change in sedentary women. AB - PURPOSE: To construct and evaluate a psychometric instrument for the assessment of behavioral change as a means for gaining insight into the development of more effective programs for promoting physical activity in women. DESIGN: A 16-item questionnaire was created and was administered three times (0, 6, and 12 months) to 181, 90, and 82 women, respectively, to determine the validity and reliability of the instrument. Participants were women 30-60 years of age, literate in English, and sedentary. METHODS: The data were analyzed using factor analysis to determine the most appropriate model for evaluating three theoretical constructs: (a) goal setting, (b) restructuring plans, and (c) relapse prevention and maintenance. RESULTS: A 3-factor model was shown to be appropriate; the instrument adequately distinguished the constructs goal setting and relapse prevention and maintenance, but did less well with the concept of restructuring plans, indicating that this concept may not be a separate entity. CONCLUSIONS: This study showed that this new instrument to evaluate behavioral change has important empirical applications. Each subscale can be used independently, depending on the needs of the investigator. This instrument will be useful for public health programs promoting physical activity in a sedentary population. PMID- 11775306 TI - Development of the Arabic language readiness to Stop Smoking Questionnaire A RSSQ. AB - PURPOSE: To develop and evaluate the psychometric properties of an Arabic language version of the "Smoking and Women Questionnaire" (SWQ) for men and women. DESIGN: The core elements of the SWQ were translated into Arabic, back translated, and pilot tested to ascertain cultural sensitivity and appropriateness for both men and women in the Eastern Mediterranean Region (EMR). A convenience sample (N = 260) of smoking and nonsmoking adults completed a demographic sheet and the Arabic Readiness to Stop Smoking Questionnaire (A RSSQ). Pre- and post tests were conducted on a smaller sample. METHODS: Researchers used methods to assure accuracy of content and understanding of concepts across cultures. Cronbach's alpha and Pearson's correlation coefficients were calculated to evaluate instrument development. FINDINGS: The scale showed internal consistency. Pre- and post test stability was supportive of respondents' consistent attitudes over 2 weeks at both the item and scale level. Construct validity was shown for both men and women in that scores for smokers were significantly lower than for nonsmokers. The alpha reliability coefficient was .78 for the total scale. CONCLUSIONS: The A-RSSQ showed initial reliability and validity for men and women. It is useful as a cost-effective means for identifying people in the EMR who are ready to stop smoking. PMID- 11775307 TI - Correlates of recent suicide attempts in a triethnic group of adolescents. AB - PURPOSE: To describe recent self-reported suicide attempts in a triethnic group of adolescents, to analyze differences in the correlates of attempts by ethnicity and gender, and to explore theoretical correlates of recent suicide attempts using a resilience framework. METHODS: Quantitative data were collected from 10,059 students in 7th, 9th, and 11th grades in Connecticut in 1996. Secondary analysis was done to compare respondents of African American, Hispanic Latino, and Caucasian ethnicities. Data were analyzed using bivariate and multivariate procedures. Logistic regression was used to identify the best set of explanatory variables for recent suicide attempts. RESULTS: The percentage of suicide attempts was significantly higher among Hispanic Latina girls (19.3%) than in any other ethnic-gender group. Significant relationships were found between recent suicide attempts and (a) family history of suicide attempt, (b) friend's history of suicide attempt, (c) history of sexual abuse, (d) history of physical abuse, and (e) environmental stress. The significant set of explanatory variables for recent suicide attempts for the three ethnic groups combined were stress, internalizing and externalizing behaviors, physical and sexual abuse, family and friend attempted suicide, social connectedness, and religious influence. CONCLUSIONS: Findings support use of a resilience model for suicide attempts among three ethnic groups. The finding of a significantly higher percentage of recent suicide attempts by Hispanic girls compared to girls in other ethnic gender groups warrants further investigation along with development and testing of culturally sensitive preventive interventions. PMID- 11775308 TI - Genetic counseling outcomes validation by genetics nurses in the UK and US. AB - PURPOSE: To validate genetic counseling outcomes with a sample of genetics nurses from the United Kingdom (UK), and to compare elements of genetic counseling outcomes with those from a sample of genetics nurses from the United States (US). DESIGN: Descriptive-comparative survey. METHODS: Concept analysis and literature review were used to designate outcomes, and genetics nurses were surveyed to validate the outcomes. A revision of Fehring's 1987 methodology for assessing content validity was used to estimate content validity and sensitivity of the genetic counseling outcomes. Data are reported on a convenience sample of 50 UK nurse members of the Association of Genetic Nurses and Counsellors. Findings were correlated with prior data from a convenience sample of 92 U.S. nurse members of the International Society of Nurses in Genetics, Inc., and data were compared between groups. FINDINGS: A significant positive correlation was found between samples of U.K. and U.S. nurses regarding components of outcomes of the genetic counseling process and between groups regarding extent of contribution of nurses to the outcomes. Strength of nursing contributions to knowledge of disease and indicators of coping varied according to country. CONCLUSIONS: Genetics nurses in the UK and US had similar definitions of outcomes of genetic counseling, but priorities of indicators differed between countries. Terminology used in measures to identify outcomes of the process of genetic counseling must be consistent with cultural norms. PMID- 11775309 TI - The relationship of social norms to use of services and caregiver burden in Japan. AB - PURPOSE: To develop an improved measure of "sekentei" (a social-psychological process that restricts behaviors that do not conform to social norms such as family caregiving) among family caregivers in Japan, and to describe the relationships among sekentei and caregiver's actual use of services, a reluctance to use services, and care burden. DESIGN: Descriptive correlational study. Family caregivers (N = 260) of impaired elders responded to a structured questionnaire. METHODS: Exploratory and confirmatory factor analyses were used to assess the construct validity of the sekentei scale for caregivers (SSC). With the SSC, the relationships among main variables were verified. FINDINGS: The SSC showed satisfactory reliability and validity. Sekentei was significantly correlated with care burden, but not to actual use or reluctance to use services. CONCLUSIONS: Sekentei is an important factor related to caregiver burden in Japan. Further research might include the extent to which sekentei is a factor in care burden in other cultures. PMID- 11775310 TI - Historical analysis of siderail use in American hospitals. AB - PURPOSE: To explore the social, economic, and legal influences on siderail use in 20th century American hospitals and how use of siderails became embedded in nursing practice. DESIGN: Social historical research. METHODS: Numerous primary and secondary sources were collected and interpreted to illustrate the pattern of siderail use, the value attached to siderails, and attitudes about using siderails. FINDINGS: The persistent use of siderails in American hospitals indicates a gradual consensus between law and medicine rather than an empirically driven nursing intervention. Use of siderails became embedded in nursing practice as nurses assumed increasing responsibility for their actions as institutional employees. CONCLUSIONS: New federal guidelines, based on reports of adverse consequences associated with siderails, are limiting siderail use in hospitals and nursing homes across the United States. Lowering siderails and using alternatives will depend on new norms among health care providers, hospital administrators, bed manufacturers, insurers, attorneys, regulators, and patients and their families. PMID- 11775311 TI - Immigrant nurses' experience of racism. AB - PURPOSE: To document and describe the experiences of immigrant nurses of colour who have filed grievances concerning their employers' discriminatory practices; and to solicit their views of existing policies and recommendations for equity in professional life. DESIGN AND METHODS: In this descriptive, exploratory study nine immigrant nurses of colour in Ontario, Canada, were interviewed between 1997 and 1998. Data were collected through face-to-face interviews and in focus groups. The discourse theory and methods of van Dijk and Essed were used to analyse the qualitative data. FINDINGS: Recurring themes were: (a) being marginalized and acknowledging and naming the racist experiences; (b) experiencing physical stress and emotional pain; (c) strategizing to cope and survive; (d) recommending policy changes. CONCLUSIONS: All nurses interviewed had experienced reprisals as a result of complaining or filing grievances and unfairness was encountered in the redress process itself. Participants recommended policy initiatives to ensure equity and fair practices in the nursing profession. PMID- 11775312 TI - [Value of antibiotype and bacteriocinotype for differentiating Shigella strains isolated in Argentina]. AB - The aim of the present work was to analyse the phenotypical characteristics of Shigella strains in order to evaluate their possible utilisation as epidemiological markers. For one year, we studied 95 strains of Shigella obtained from stool specimens of patients with dysentery. Bacteria came from various health care centres in the states of Chaco and Corrientes (Argentina). Bacteria were identified by using classical biochemical methods. All strains were serotyped and susceptibility patterns were determined using thirteen antibiotics. Bacteriocin typing was determined by the sensitivity to piocins of Pseudomonas aeruginosa and to marcescins of Serratia marcescens. Colicin production in S. sonnei was also studied. Among all the strains examined, the most prevalent was Shigella flexneri (82%) followed by Shigella sonnei (18%). The most frequent serotype among S. flexneri was 2 (93%), followed by serotypes 6 (4%), 1 (1.5%), and 3 (1.5%). S. sonnei strains were classified in 7 antibiotypes, 6 piocin types, 3 marcescin types, and 4 colicin types. Strains of S. flexneri type 2 were divided among 14 antibiotypes, 4 piocin types and 2 marcescin types. Simpson's index of diversity was applied to evaluate the discriminatory power of studied typing methods, both alone and combined. Our results indicate that when taken independently, none of the evaluated typing methods had discriminative power, but when taken together, they may be successfully used for the epidemiological typing of Shigella strains. PMID- 11775313 TI - [Persistent external biliary fistula after surgery for hepatic hydatid cyst]. AB - Post-operative persistent biliary fistulae due to hydatid cysts are difficult to manage. We report 3 cases of external biliary fistulae complicating surgery for hepatic hydatid cyst (2 cases) and intraperitoneal hydatid cyst (1 case). Endoscopic sphincterotomy was successful with closure of the fistulae in all patients. This procedure should be the first-line treatment for post-operative external biliary fistulae related to liver hydatid disease. Usually difficult and haemorrhagic surgery can thus be avoided. PMID- 11775314 TI - [Appendicitis in Niger: current prognosis]. AB - Acute appendicitis remains one of the most frequent emergencies in abdominal surgery. Surgery is usually straightforward and prognosis excellent. However, outcome depends essentially on how soon diagnosis is made. In Niger, the 1990s were marked by the development of private medicine and the deterioration of services in state health structures (health centres and hospitals). The goal of this prospective study, carried out over 24 months (March 1997-March 1999) was to analyse existing appendicitis prognosis in our country. The study population was made up of 362 patients and we based our survey on a number of factors found in the medical literature, and in particular on a similar study conducted in the same hospital in 1989 by another group of surgeons. Delays in diagnosis and thus therapy still today tends to transform prognosis for simple acute appendicitis into that of peritonitis. The numerous and varied post-operative complications keep the mortality rate at 4%. PMID- 11775315 TI - [Prognosis of strangulated inguinal hernia in the adult: influence of intestinal necrosis. Apropos of 34 cases]. AB - The aim of this study was to determine the outcome for patients treated for strangulated inguinal hernia with intestinal resection for gangrenous. Between May 1997 and November 1998, 124 patients were admitted to our hospital for acute intestinal obstruction; 34 of them were treated for strangulated inguinal hernia and 17 underwent an intestinal resection. The outcome for the 34 patients with strangulated hernias were analysed retrospectively. Strangulated inguinal hernia occurred in young patients (80 per cent of our patients were aged under 45 years) and strangulation had evolved over an average of 2.5 days. The clinical picture was simple strangulated hernia in 10 cases, with intestinal obstruction syndrome in 15 cases, peritonitis in 3 cases, phlegmonous hernia in 4 cases, and fistulae in one case. Fifty per cent of patients had intestinal resection with poor means of resuscitation. This resection concerned 80 per cent of patients with strangulation lasting over 72 hours. Surgical repair of hernia was performed in 24 cases at the same time. There were numerous complications, notably: wound sepsis (16 cases), post-operative peritonitis (3 cases) and multiple system failure (12 cases). The mortality rate was 40 per cent and concerned 86 per cent of patients with small bowel necrosis and 89 per cent of those admitted after 96 hours of strangulation. PMID- 11775316 TI - [Anthropometric indices used for the diagnosis of malnutrition in adolescents and adults: review of the literature]. AB - The International Dietary Energy Consultative Group, sponsored by the World Health Organization (WHO), has done most of the research conducted in the field of adult malnutrition in the late 1980's. These studies were carried out mainly in populations suffering from chronic malnutrition, and led to the current WHO recommendations for the diagnosis and classification of adult malnutrition. Body Mass Index (BMI) is the gold standard to be used in adults, with the following cut-off points identified: 16.0, 17.0 and 18.5. The good correlation observed between BMI and Middle Upper Arm Circumference (MUAC) led to the determination of corresponding cut-off points. However, the very few field studies available in the literature are in favor of a lowering of the BMI cut-off points during nutritional emergencies. Several questions need to be answered through field research, mainly concerning the type of indicator best predicting the risk of death, and the type of indicator to be used in adolescents, pregnant women and older people. PMID- 11775317 TI - [Coxiella burnetii pneumopathy on return from French Guiana]. AB - Q fever is a worldwide zoonosis but is not often a common cause of fever among travellers returning from the tropics. We report a case of acute Q fever, revealed by a pneumonia and acquired by a traveller in French Guyana. The chest radiography showed alveolar opacities and pleural effusion. Biological abnormalities were elevated liver enzyme levels and thrombocytopenia. The patient improved or the third day of antibiotic treatment. She mentioned that 3 other people she lived with during her trip had been diagnosed with Q fever. A common source outbreak was then suspected. They all stayed in the same farm in French Guyana. Animal exposure occurred there, in particular with a goat and a dog (both were parturient). The disease was probably transmitted by airborne dust to our patient, as no other vectors of transmission were found. Since the clinical presentation of Q fever is not specific, in order for the physician to diagnose it, he must have an awareness of the disease. Our case emphasised that looking for risk factors of Coxiella burnetii exposures is particularly important. Amongst them, the most important seems to be contact with farm animals. The clinician should thus try to trace such a possible contact when treating a case of traveler's Q fever. PMID- 11775318 TI - [Apropos of 2 rare severe surgical complications from the use of intramuscular and intrarectal quinine]. AB - Quinine by intramuscular or intrarectal injection has been found to be the best treatment for malaria in Niger, particularly in field health centres where the use of solutions can pose problems. There have been several reports of complications following injections, usually due to technical error or to the toxic side effects of quinine. In our hospital, we treated two such rare complications consisting of a case of coxal osteoarthritis induced by intramuscular injection and a case of anorectal necrotising induced by intrarectal injection. The occurrence of such life-threatening events could be reduced in frequency by teaching health personnel about techniques of quinine administration as well as its dangers. PMID- 11775319 TI - [Final prenatal consultation in the district of Bamako: critical analysis of the procedures, results and perspectives for improvement]. AB - The context in which antenatal care is organised and practiced in the Bamako district has cast doubt on its efficacy. We conducted a survey in order to evaluate the quality of final prenatal consultations, using a sample of 169 expecting mothers selected amongst the patients of 4 family planning clinics in the Bamako district (Republic of Mali). Our investigation revealed that standard procedures are still unevenly carried out, although this is the last opportunity to detect and manage pregnancies with risk factors. Obstetrical results remained statistically similar both for the surveyed and non-surveyed women. However, any conclusions as to the efficacy of antenatal care must be drawn with caution given problems of confounding as well as the sampling method used in our survey. PMID- 11775320 TI - [Epidemiological aspects of tuberculosis in middle west of Madagascar]. AB - We conducted a 5-year (1989-1993) retrospective analysis on a series of patients screened and treated for tuberculosis in order to determine the epidemiological aspects of the disease in mid-western Madagascar. Pulmonary forms affected 97% of patients, and predominantly men (sex ratio: 1.4); 83% of patients with pulmonary tuberculosis were coughing up acido-alcoholo-resitant bacilli. Haemoptysis and general deterioration, the most frequently met pathological signs, were observed respectively in 62% and 24% of cases. This explains the high rate of hospitalisation (42%), especially for patients with difficult access to services. Significantly, in terms of socio-professional category, live-stock breeders and farmers represented 32% of notified cases, and cattle-traders 18%. We draw attention to the possible role played by Mycobacterium bovis in human case findings in a region characterised by cattle-breeding. PMID- 11775321 TI - [Microbiological surveillance: viral hemorrhagic fever in Central African Republic: current serological data in man]. AB - An investigation was conducted between 1994 and 1997 in forested areas of the Central African Republic (CAR) to determine the seroprevalence of IgG antibodies against several haemorrhagic fever viruses present in the region. Sera were obtained from 1762 individuals in two groups (Pygmy and Bantu locuted populations) living in 4 forested areas in the south of the country. Sera were tested for IgG antibodies against Ebola, Marburg, Rift Valley fever (RVF), Yellow fever (YF) and Hantaviruses by enzyme immunoassay (EIA), and against Lassa virus by immunofluorescent assay. The prevalence of IgG antibodies was 5.9% for Ebola, 2% for Marburg, 6.9% pour RVF, 6.5% for YF, 2% for Hantaan. No antibodies were detected against Lassa, Seoul, Puumala and Thottapalayam viruses. No IgM antibodies were detected against RVF and YF viruses. The distribution of antibodies appears to be related to tropical rain forest areas. This study indicates that several haemorrhagic fever viruses are endemic in forested areas of the CAR and could emerge due to environmental modification. PMID- 11775322 TI - [The state of vector-borne diseases in Indonesia]. AB - From epidemiological point of view, Indonesia is an extremely interesting area owing its insular structure and ecological, anthropological, cultural and economical diversity. As everywhere, vector-borne diseases are the result of complex and variable epidemiological systems, subject both to biogeographical rules and human activity. Two main arboviroses are present in Indonesia: dengue and Japanese encephalitis. Dengue appears as an endemoepidemic disease and is mostly circumscribed to urban areas. Haemorrhagic cases were first observed in 1968; since then, the incidence has been constantly increasing and the disease is now one of the principal causes of child lethality. Japanese encephalitis is a rural endemic disease transmitted by rice-field mosquitoes; its incidence remains relatively low since pigs, which are usual link-hosts for the virus, are uncommon in this mainly Muslem country. Human clinical cases are recorded from non-Muslem islands such as Bali or Irian Jaya which raises the question of immunisation for travellers. Recently, Japanese encephalitis was observed on east of the Wallace line which had been considered as the eastern cut-off line. Malaria is common throughout the country, Plasmodium vivax being the most frequent species. Some of the Anopheline vectors are related to brackish water as are coastal species; others have been favoured by rice growing. Several species bite and rest outdoors, rendering control measures complex. Moreover, chloroquine resistance is increasing in both P. falciparum and P. vivax. All three filaria species responsible for human lymphatic filariasis exist in Indonesia. Bancroft filariasis is present in rather limited foci on most of the islands; malayan filariasis is very prevalent on many islands, mostly in coastal areas, and Timor filariasis exist only on a few small islands. These parasitic diseases are cumulative and do not practically endanger the health of travellers. In the past, plague was common on Java island, but today, human cases are very rare. Scrub typhus is prevalent everywhere, as is murine typhus, being very frequent in harbour cities and one of the main causes of hospitalisation for febrile syndromes.. On the whole, the situation of several of these diseases has been worsening in Indonesia for about thirty years. Although epidemiological situations constantly evolve, two recent occurrences should be paid particular attention: -transmigration which is now a national priority and greatly facilitates the spread of many pathogens, arboviroses or chloroquine-resistant plasmodia, but also of rats, mosquitoes, etc. -deforestation due either to land farming by Javanese transmigrants or to sudden climatic changes such as El Nino in 1997. Such deep ecological transformations may have considerable and unforeseeable consequences on the epidemiology of vector-borne diseases in Indonesia. PMID- 11775323 TI - [For a better estimation of the prevalence of intestinal parasitism in the Tunis region]. AB - The prevalence of intestinal parasitism is generally based on the results of a single stool specimen which probably underestimates the real situation. In order to propose a coefficient for correction, we examined three stool specimens taken from 112 asymptomatic children. Intestinal parasites other than Enterobius vermicularis were detected in 29 subjects (26%). For those specimens that tested positive, 41% of children had infection detected in all three stool specimens; 21%--in two specimens and 38%--in only one. If we assume that the sensitivity of three stool specimen examinations is 100%, then the calculated sensitivity of one examination is equivalent to 68%. This gives an underestimation of the prevalence of 32%. This underestimation is not homogenous for all species. As regards Giardia intestinalis it is 35%, but for other species it would have to be calculated from a larger sample. PMID- 11775324 TI - [Reduced morbidity of schistosomiasis: report from an expert workshop on the control of schistosomiasis held at CERMES (15-18 February 2000, Niamey, Niger)]. AB - Schistosomiasis remains a problem for public health in sub-Saharan Africa. Despite past efforts, cases have not decreased significantly. Schistosoma haematobium and S. mansoni are endemic in all the West African countries. The distribution of both parasites is focal. During a workshop held at CERMES in Niamey, in February 2000, a group of experts recommended that schistosomiasis control be considered as a public health priority in all the endemic West African countries, and National Control Programmes rapidly implemented. The objective of these control programmes would be to reduce schistosomiasis-related morbidity. Case detection should be based on clinical symptoms such as haematuria or bloody diarrhoea, and be carried out at two levels: health care centres and schools, in order to reach patients and school-age children. Health workers should be trained in case detection and community based control of schistosomiasis. The assembled experts advocated the use of praziquantel dosed at 40 mg.kg-1, which therefore must be made available and accessible in outlying areas. Associated measures consist of sanitation, water supply and health education, especially aimed at improving patients' treatment-seeking behaviour. A West African network for schistosomiasis control was created during the workshop. It runs on the Web site of CERMES as network co-ordinator. (http://www.mpl.ird.fr/cermes/). PMID- 11775325 TI - [Traditional tattoos with neurological diseases in Togo]. AB - In Africa, there are two types of health systems: the modern system and the traditional one. Traditional medicine attracts more patients, because it is more financially accessible and corresponds to cultural representations of disease in society. Traditional therapeutic tattoos are not well known by the conventional health system in West Africa, although they are commonly used by traditional healers. We report here our experience of these tattoos. We examined the skin of 36,000 patients in the neurological department of the teaching hospital of Lome from 1985 to 1995. We found three types of tattoos amongst patients. The first are tribal or social tattoos: they are large, homogeneous, located on exposed parts of the body and can be seen easily by others (fig 1: g, h, i), whilst therapeutic tattoos are slight and hidden under clothes and can also be repeated (heterogeneous). The second type of tattoo is one that reveals the patient's pathological history. The third is linked to the motive of consultation. Seventy five per cent (75%) of patients had traditional therapeutic tattoos. Epilepsy tattoos are slim, located on the forehead (fig 1a); peripheral facial paralysis tattoos are found on the facial nerve (fig 1 b). In cases of peripheral neuropathy, tattoos are symmetrically distributed on hands and legs (fig 1 f). As for medullar compression, the highest tattoos correspond to the level of compression. Studying the localisation, age, and aim of tattoos brings to light their diagnostic, prognostic, and epidemiological interests. Skin can thus reveal itself to medical staff as an open, though coded, medical file. They need only to learn how to read it. PMID- 11775326 TI - [Edmond Sergent (1876-1969) and the Pasteur Institute of Algeria]. AB - Edmond Sergent, supported by a distinguished team of colleagues, directed the Pasteur Institute of Algeria for over 60 years, from 1900 to 1963. As a student of Emile Roux, Sergent had received a Pasteurian training. His institute devoted extensive study to malaria. Sergent defined the concept of prevention and extended it to other pathologies. For many years, the Institute persevered in carrying out successful antimalarial campaigns such that Algeria was freed of the disease. In 1916-1917, Sergent and his brother were called upon to organise anti malarial efforts for the Armee d'Orient. By way of systematic and energetic curative and prophylactic measures, they were able to eradicate the disease. In 1908, the Sergent brothers were the first to discover the role of the louse in the transmission of another disease, relapsing fever. The Pasteur Institute team also discovered the sand fly vector which transmits the parasite causing leishmaniasis. The Sergents found a new form of oculonasal myiasis, called "Thimni". In addition, they led effective campaigns against tuberculosis based on BCG vaccination administered throughout Algeria. The Pasteur Institute of Algeria conducted important research in plant and animal diseases. For example, they detected a trypanosome agent causing dromedary "debab", as well as its vector, the horsefly. They also studied in depth bovine piroplasmosis, which causes widespread and destructive disease, and demonstrated the role of the tick in promoting transmission generally. Their work in botany included the discovery that a Fusarium-type fungus was the causal agent for "baioudh", the main disease of date palms. They also demonstrated the basic role of the fruit fly in alcoholic grape fermentation. PMID- 11775327 TI - Epidemiological understanding of Taenia tapeworm infections with special reference to Taenia asiatica in Korea. AB - In endemic areas of Taenia tapeworms in Korea, most of the reports showed that T. saginata was dominant over T. solium, but eating pigs is the dominant habit over eating cattle. Why do they have more T. saginata despite lower consumption of beef? This problem actually has long been recognized but until recently there has been no intensive trial to give a scientific explanation on this epidemiological enigma. By summing up the data published between the years 1963 and 1999, the ratio of armed versus unarmed tapeworms in humans was estimated at approximately 1:5. The ratio of pig-eaters versus cattle-eaters, however, was approximately 5:1. This inconsistency could be explained with the recently described T. asiatica, which infects humans through the eating of pig's viscera. We re evaluate the importance of the consumption of visceral organ of pigs. leading us to an improved epidemiological understanding of the T. asiatica infection together with co-existing T. saginata and T. solium in Korea. PMID- 11775329 TI - Incidence patterns of vivax malaria in civilians residing in a high-risk county of Kyonggi-do (province), Republic of Korea. AB - The characteristics of vivax malaria epidemics along the demilitarized zone (DMZ) in the Republic of Korea has been established by the early surveillance data. To further characterize the epidemic, data of civilian patients microscopically diagnosed with malaria from 1995 through 2000 were analyzed in Yonchon-gun (county). Malaria incidence was greater in male civilians > 30 years of age (p < 0.05). The annual parasite index was significantly higher in those living in the administrative areas (Myeon) traversed by DMZ than those living in Myons not traversed by DMZ (p < 0.05). Analysis according to the distance (4 to 14 km) from DMZ showed that people living in villages close to DMZ had higher annual parasite indices than those living in villages remote from DMZ (p for trend < 0.05). Civilians living in Myeons with plains and located in northwestern part of the county had higher annual parasite indices than those living in hilly Myeons located in southeastern part of the county (p for trend < 0.05). These findings suggest that the contraction of vivax malaria is related with night-time outdoor activities, and that the distance from DMZ is a risk factor. In this area, the flying distance of infected vector mosquitos can explain the annually repeating occurrence of civilian cases. PMID- 11775328 TI - Control of clonorchiasis by repeated treatments with praziquantel. AB - The present study aimed to evaluate control efficacy of clonorchiasis by two schemes of repeated treatment with praziquantel at two endemic villages in China. Residents of one village at Guangxi Autonomous Region were treated and examined 6 monthly and of another at Liaoning Province 12-monthly. In residents that took 25 mg/kg x 3 (total 75 mg/kg) of praziquantel every 6 months for one year the egg positive rate showed a significant drop from 69.0% to 17.1%. In contrast, a group of same praziquantel medication once showed a slight marginal decrease in the egg rate from 18.9% to 12.2% after one year. Of 39 subjects examined 3 times, 56.4% were cured, 7.7% persistently positive, one (2.6%) reinfected after cure or newly infected, but 25.6% were persistently negative. The present finding suggests that 6-monthly medication with 75 mg/kg of praziquantel should effectively lower the prevalence but incomplete for control of clonorchiasis in heavy endemic areas. PMID- 11775330 TI - Analysis of vivax malaria cases in Gangwon-do (province), Korea in the year 2000. AB - A total of 827 malaria cases were reported in the Gangwon-do in the year 2000. There were 18.2 cases per 100,000 inhabitants. There were 283 cases among civilians and 544 cases among the military. 90.6% of cases were reported in Cheorwon--(531), Hwacheon--(152), and Goseong--(66) gun (county), which bordered the demilitarized zone (DMZ). A distinct feature pertaining to the malaria cases in Gangwon-do is that the number of cases has increased about two times over the last year. The mean time from the beginning of symptoms to malaria diagnosis was five days. Control systems for malaria by public health organizations and military organizations are well maintained, but were not able to reduce the malaria prevalence rate. The cause for the increase in pattern of the malaria cases in Gangwon-do may be caused by the spreading of prevalent areas of malaria to the east. Continuous endeavor such as early detection of cases, early treatment, education on clinical symptoms and prevention of mosquito bites with repellent and mosquito nets will help to reduce the infection rate of malaria in Gangwon-do. PMID- 11775331 TI - Antigenic profile and localization of Clonorchis sinensis proteins in the course of infection. AB - In the course of Clonorchis sinensis infection, antigens presented to the hosts may be in a close relation to growth of the fluke. The antigenic proteins stimulating IgG antibody production were chronologically identified by immunoblot and localized by immunohistochemical staining. In the early stage of infection until 12 weeks post-infection (PI), antigens were proteins with molecular mass larger than 34 kDa which were derived from the tegument, testes and intrauterine eggs. After 20 weeks PI, antigens recognized were 29, 27 and 26 kDa proteins from the intestine, excretory bladder and reproductive organs. It is suggested that the tegumental proteins are the most potent antigens and the excretory-secretory proteins with middle molecular mass of 26-45 kDa contribute to the high level production of antibodies after 20 weeks of the C. sinensis infection. PMID- 11775332 TI - Analysis of polymorphic region of GAM-1 gene in Plasmodium vivax Korean isolates. AB - The identification, characterization and quantification of Plasmodium sp. genetic polymorphism are becoming increasingly important in the vaccine development. We investigated polymorphism of Plasmodium vivax GAM-1 (PvGAM-1) gene in 30 Korean isolates. The polymorphic region of the PvGAM-1 gene, corresponding to nt 3792 4029, was amplified using polymerase chain reaction (PCR) followed by sequencing. All of the P. vivax Korean isolates were one type of GAM-1 gene, which were identical to that of the Belem strain. It is suggested that PvGAM-1 could not be used as a genetic marker for identifying or classifying P. vivax Korean isolates. It revealed that the polymorphic pattern was acquired basically by duplication and modification or deletion event of a 33 bp-motif fragment ended by poly guanine (G) and that there were at least three complete and one partial 33 bp motif sequences within the polymorphic region in the longest cases such as those of South Korean and Belem isolates. In addition, we clustered P. vivax isolates with parsimonious criteria on the basis of PvGAM-1 polymorphic patterns (insertion/deletion patterns). PMID- 11775333 TI - Diphyllobothrium latum infection after eating domestic salmon flesh. AB - Diphyllobothrium latum infection in human is not common in Korea and only thirty seven cases have been reported since 1921. We report two cases of fish tapeworm infection after ingestion of raw cherry salmon (Oncorhynchus masou) caught in the domestic river. Among four family members who ate together raw salmon flesh six months ago, just two, mother and daughter, were infected. It is our expectation that the salmon associated tapeworm infections would be enlisted as one of the major parasitic problems with the growing consumption of salmon in Korea. PMID- 11775334 TI - Infection rates of Enterobius vermicularis and Clonorchis sinensis of primary school children in Hamyang-gun, Gyeongsangnam-do (province), Korea. AB - The egg positive rate of Enterobius vermicularis and Clonorchis sinensis of school children in the rural area was studied in Hamyang-gun, Gyeongsangnam-do in Korea. Cellotape anal swab and formalin ether concentration methods were performed one time to 720 primary school children. The total egg positive rate of E. vermicularis was 12.6% in two schools (Baekjeon and Wiseong). In the Baekjeon and Wiseong primary school, the egg positive rate of E. vermicularis was 4.6% and 13.4%, respectively. Pinworm egg positive rate was 17.6% in the lower grades (1st, 2nd and 3rd), and 7.7% in higher grades (4th, 5th and 6th). The total egg positive rate of male and female was 12.6% and 12.7%, respectively. The egg positive rate of C. sinensis of Baekjeon and Wiseong primary school was 1.5% and 0.46%, respectively. The total egg positive rate of C. sinesis was 0.56%. This survey showed that continuous education and chemotherapy is necessary to treat and prevent reinfection of E. vermicularis. In the case of C. sinensis, health education for school children is recommended to prevent potential infection of adolescents. PMID- 11775335 TI - Enterobius vermicularis egg positive rates in primary school children in Gangwon do (province), Korea. AB - A survey of the infection rate of Enterobius vermicularis among students in 4 primary schools located in Gangwon-do (Province) was done from May to June 2001. Among the 398 examinees, 39 (9.8%) were infected with E. vermicularis demonstrated by the adhesive cellotape anal swab method. The infection rates ranged from 8.3% to 11.8% among the four schools. The infection rate of males and females was 10.7% and 7.7% respectively. The first grade students showed the highest infection rate, 28.7%. The confirmed cases were treated with albendazole three times at an interval of 15 days. We were able to confirm that E. vermicularis infection is still prevalent among students in Gangwon-do, Korea. PMID- 11775336 TI - Corbicula fluminea (Bivalvia: Corbiculidae): a possible second molluscan intermediate host of Echinostoma cinetorchis (Trematoda: Echinostomatidae) in Korea. AB - More than 1,500 clams of Corbicula fluminea, the most favorable food source of freshwater bivalves in Korea, were collected from 5 localities to examine cercarial and metacercarial infection with Echinostoma cinetorchis. Although 3 clams infected with suspicious E. cinetorchis metacercariae out of 200 specimens collected at Kangjin, Chollanam-do were detected, no cercarial and metacercarial infections with E. cinetorchis were observed in field-collected Corbicula specimens. In the susceptibility experiments with laboratory-reared clams, those infected with miracidia of E. cinetorchis did not release their cercariae up to 60 days after infection. To confirm the identity of second intermediate host of E. cinetorchis experimentally, a total of 30 clams were exposed to the cercariae from Segmentina hemisphaerula that had been infected with miracidia of E. cinetorchis. The clams were susceptible to cercariae of E. cinetorchis with an infection rate of 93.3%. Metacercariae from clams taken more than 7 days after cercarial exposure were fed to rats (S/D strain), and adult worms of E. cinetorchis, characterized by 37-38 collar spines on the head crown, were recovered from the ileocecal regions. This is the first report of C. fluminea as a possible second intermediate host of E. cinetorchis. PMID- 11775337 TI - [Incipient gallbladder carcinoma. Clinical and pathological study and prognosis in 196 cases]. AB - BACKGROUND: There is little information about the behavior of early gallbladder carcinoma. AIM: To report the clinical and pathological features of 196 patients with early gallbladder carcinoma. MATERIAL AND METHODS: All patients with gallbladder cancer diagnosed between 1988 and 1997 were reviewed. In 703 of 829 patients, there was information about clinical features and follow up, and were included in this study. All gallbladders were subjected to a complete mapping. When neoplastic cells involved only the mucosa or muscular layer, the tumors were considered as early. RESULTS: One hundred ninety six patients had an early carcinoma (161 women, aged 57.5 years and 35 male, aged 63.4 years). One hundred twenty eight tumors were located in the mucosa and 68 in the muscular layer. Patients with tumors involving the mucosa were younger than those with tumors involving the muscular layer. All tumors were adenocarcinomas, 66% were well differentiated and 32% moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92%. Subjects of less than 40 years old had a 100% survival at 5 years. A hepatic and lymph node resection was done in 12 patients with tumors infiltrating the muscular layer but in only one, the tumor infiltrated the liver. No difference in survival was observed when a simple cholecystectomy or radical surgery was done. CONCLUSIONS: Nearly 25% of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study. Simple cholecystectomy is curative for this type of gallbladder cancer. PMID- 11775338 TI - [Effect of oral and intramuscular vitamin K on the factors II, VII, IX, X, and PIVKA II in the infant newborn under 60 days of age]. AB - BACKGROUND: Neonates on exclusive breast feeding that do not receive vitamin K at birth are at higher risk hemorrhagic disease of the newborn. AIM: To compare the effect of oral or intramuscular administration of vitamin K1 (VK1), on clotting factors II, VII, IX, X and PIVKA II, in children until the 60 days of age with exclusive breast feeding or mixed feeding. PATIENTS AND METHODS: Forty healthy full term infants, distributed in two groups, A: 20 with mixed feeding (formula feeding and breast-feeding) and B: 20 with exclusive breast feeding, were studied. Nine infants of each group received 1 mg of VK1 intramuscularly and eleven 2 mg VK orally 5 ml of cord blood was collected initially from each infant. Venous blood samples were taken on 15, 30 and 60 days of age. RESULTS: All factors increased in a progressive form reaching levels over 50% at 60 days of age, in both groups. PIVKA II decreased significantly during the study period (p < 0.01). Factor II increased more in children with mixed feeding that received intramuscular vitamin K, than in the rest of study groups. No other differences between groups were observed. No infant had an abnormal bleeding during the study period. CONCLUSIONS: Oral administration of vitamin K is as effective as the intramuscular route in the prevention of the hemorrhagic disease of the newborn. PMID- 11775339 TI - [Coronary reoperation: a 16 years retrospective analysis]. AB - BACKGROUND: Coronary artery bypass grafting (CABG) reoperation is being performed with increasing frequency. AIM: To assess the early and long term results of coronary reoperations in our institution and to identify prognostic factors. PATIENTS AND METHODS: 214 patients subjected to coronary reoperations between 1983 and 1999 were retrospectively studied. RESULTS: Mean age was 64.2 years (range 42-79 years), 202 (94.4%) were male and 12 (5.6%) female. The mean interval between the operations was 125.7 months (range 6-252 months). 10 (4.6%) were emergency surgeries. Overall operative mortality was 5.6% (11 deaths) and in 5 patients (3.4%) a perioperative myocardial infarction was noted. Univariate analysis identified moderate or severe left ventricular failure (p = 0.048) as predictor of increased operative mortality, meanwhile age over 75 years (p = 0.02) and moderate or severe left ventricular failure (p = 0.01) were identified as predictors of increased in hospital mortality in the multivariate analysis. Follow up of in hospital survivors (mean interval 65 months, range 4 to 190 months) documented a 5 years survival rate of 82.9%, a 10 years survival rate of 73.1% and a 15 years survival rate of 53.4%. Moderate or severe left ventricular failure (p < 0.0001) and emergency surgeries (p = 0.007) were identified as factors influencing the late survival in the stepwise logistical regression analysis. Multivariate analysis identified left ventricular failure (p = 0.01) and peripheral vascular disease (p = 0.01) as predictors of decreased late survival. CONCLUSIONS: Coronary reoperation has a low mortality in patients with a normal ventricular function and also has an excellent overall and disease free survival in the first 10 years of follow up. Left ventricular function is an independent risk factor increasing in hospital and late mortality. PMID- 11775340 TI - [Preliminary results of laparoscopic video esophagomyotomy in patients with esophageal achalasia]. AB - BACKGROUND: Laparoscopic esophagomyotomy is becoming a good alternative to pneumatic dilatation, injection of botulinic toxin or classical surgery in the treatment of achalasia. AIM: To report the results of laparoscopic esophagomyotomy in patients with achalasia. PATIENTS AND METHODS: Nineteen patients with achalasia, nine women, aged 9 to 66 years old, operated between 1996 and 2001 are reported. RESULTS: There was no surgical mortality. One patient had a subphrenic abscess due to an unnoticed tear of the esophageal mucosa. During surgery, esophageal mucosa was perforated in 4 patients, that was sutured in three. One patient with an extensive tear of the mucosa required conversion to classical surgery. Patients were followed for 2 to 48 months. Radiological controls showed a significant increase in the diameter of gastroesophageal junction and a diameter reduction of the mid third esophageal segment. Lower esophageal pressure was significantly reduced. All patients experienced a weight increase and reduction of dysphagia. CONCLUSIONS: Laparoscopic esophagomyotomy is a safe an effective therapeutic alternative for achalasia. PMID- 11775341 TI - [Helicobacter pylori: cagA analysis and vacA genotyping in Chile. Detection of a s2/m1 strain]. AB - BACKGROUND: The genes cagA and vacA encode H pylori virulence factors. AIM: To genotype these genes in H pylori strains isolated from patients with upper gastrointestinal symptoms. MATERIAL AND METHODS: We studied 50 patients who underwent an upper gastrointestinal endoscopy, with positive culture for H pylori. Detection of cagA and vacA genotyping was done using polymerase chain reactions. RESULTS: The gene cagA was detected in 19 samples (38%). Signal sequences s1 and s2 of vacA gene were detected in 16 samples each (32%). There was simultaneous amplification of s1 and s2 in 6 samples and they were not detected in 9 samples. The middle region of vacA was m1 in 9 samples, m2 in 29 samples and there was simultaneous amplification of m1 and m2 in 12 samples. In 16 samples (32%), more than one type of signal sequence or medial region was detected. Of those patients in whom vacA was the only genotype detected, 15 were s2/m2, 7 were s1/m1, 4 were s1/m2 and 1 was s2/m1. CONCLUSIONS: In these patients, the infection with cagA- H pylori strains, predominates, the prevalence of infection with s1 or s2 strains is similar and the predominant medial region is m2. PMID- 11775343 TI - [Central nervous system malformations in a Clinical Hospital of Universidad de Chile and in Chilean maternity hospitals that participated in the Latin American Collaborative Study of Congenital Malformations (ECLAMC)]. AB - BACKGROUND: In Chile, the rates of central nervous system congenital malformations at birth remain high, when compared with the rest of the world. AIM: To report the rates of central nervous system congenital malformations in Chilean hospitals. MATERIAL AND METHODS: Using the ECLAMC protocol, every malformed newborn or stillbirth, weighing more than 500 g at birth is registered using a standard protocol, and the next non malformed child of the same sex born in the same hospital is assigned as control. RESULTS: The rates of central nervous system congenital malformations are higher at the University of Chile Clinical Hospital than in the rest of Chilean hospitals or Latin American Hospitals. There are significantly higher rates of anencephalia in Concepcion and spina bifida in Valdivia, Rancagua and Concepcion. In the University of Chile Clinical Hospital, global annual rates have a negative slope of -0.0259 per 1000 born alive, with a correlation coefficient of -0.125 (p < 0.05). The slope is positive among children born alive, with an annual rate increase of 0.071. Among stillbirths, the slope is -0.47 per 1000 born alive. Sixty two percent of malformed children were female. Among children with neural tube defects, 30% had a malformed relative and, of these, 66% had the same malformation. CONCLUSIONS: Family clustering of neural tube defects, supports the influence of a genetic factor influencing their appearance. PMID- 11775342 TI - [Biological, familial and metabolic characteristics of infantile and juvenile obesity]. AB - BACKGROUND: Obesity is the most prevalent nutritional disease in people of less than 20 years old. AIM: To report biological, familial and metabolic characteristics in obese children. PATIENTS AND METHODS: A retrospective review of 187 children seen at obesity clinics and that had a complete metabolic study. RESULTS: Ninety five prepuberal and 92 puberal children, aged 8.7 +/- 2.2 and 12.6 +/- 2.2 years old respectively, were studied. Body mass index was over 4 standard deviations in 48.4% of prepuberal children and in 39.1% of puberal children. Paternal obesity was twice more prevalent (30.2%) than in the general population. The daily caloric intake and basal metabolic rate (BMR) were within the normal range; nevertheless there was a positive caloric balance due to minimal physical activity. The mean daily fat intake was normal (26.4 +/- 8.5 and 25.3 +/- 9.1% of total calories in prepuberal and puberal children respectively). The daily fiber intake was under 70% of recommendation. The total cholesterol was over 200 mg/dl in 26.6 and 23.9% of prepuberal and puberal children. LDL cholesterol was over 130 mg/dl in 27.3 and 26.6% and triacylglycerol was over 150 mg/dl in 16.9 and 25% of prepuberal and puberal children respectively. Basal serum insulin was over 20 uIU/ml in 27.7 and 42.2% of prepuberal and puberal children, respectively. Post glucose serum insulin was over 60 uIU/ml in 40 and 63% of prepuberal and puberal children, respectively. CONCLUSIONS: Infantile and juvenile obesity is a chronic disease with a high incidence of metabolic alterations. PMID- 11775344 TI - [The six minute walking test elicits lung hyperinflation in patients with severe chronic obstructive lung disease]. AB - BACKGROUND: Exercise tolerance in patients with COPD is highly variable and poorly related to airways obstruction assessed by FEV1. These patients develop dynamic hyperinflation (DH) during an incremental exercise test which can be evaluated through a reduction in inspiratory capacity (IC). AIM: To evaluate: a) if the six minute walking test (6 MWD) induce DH reducing IC, b) if the reduction in IC is related to tidal expiratory flow limitation at rest (FL). SUBJECTS AND METHODS: Thirty eight stable COPD patients (28 FL and ten non FL during resting breathing, determined by the negative pressure technique). Inspiratory capacity was measured before and immediately after the 6 MWD test. Dyspnea, SpO2 and heart rate were measured before and after the test. RESULTS: Inspiratory capacity was lower in FL patients as compared to patients without FL (p < 0.005). Although no differences were found between groups in 6 MWD, dyspnea and HR, a significant reduction in IC after the walking test was observed only in FL patients (p < 0.0001). In addition, SpO2 fell significantly (p < 0.0001) after walking in the same group. CONCLUSIONS: Our results demonstrate that a moderate exercise such as the walking test induces DH and hypoxemia in patients with COPD and FL and stresses the importance of assessing DH by measuring IC in these patients. PMID- 11775345 TI - [Hypothalamic hamartoma causing precocious puberty: A case report]. AB - Hypothalamic hamartomas are non neoplastic lesions that may cause precocious puberty with or without complex seizures, personality disorders and mental retardation. We report a 14 years old male that had a precocious puberty at the age of 11 and a prolonged episode of altered sensorium with automatism, that was diagnosed as a complex seizure. Physical examination showed a sexual development classified as Tanner stage III-IV, a height of 168 cm and a weight of 61 kg. Neurological examination was normal. A CAT scan showed a 13 x 13 x 9 mm mass in the suprasellar cistern, between the infundibulum and the brain stem, without exerting a mass effect over adjacent structures. It was diagnosed as an hypothalamic hamartoma. PMID- 11775346 TI - [Diabetes mellitus induced by olanzapine. A case report]. AB - Atypical antipsychotics are widely used in psychotic disorders, refractory to conventional neuroleptic agents. They induce minimal extra pyramidal side effects, probably due to their greater affinity for certain dopaminergic receptors. However, this polyreceptor affinity may be responsible for the development of other side effects. We report a 48 years old male drinker and addicted to cocaine, that after two months of Olanzapine use, developed a severe diabetes mellitus with fasting blood glucose values reaching 514 mg/dl. When he was admitted to the hospital, physical examination was normal and his body mass index was 28 kg/m2. Olanzapine was discontinued and blood glucose values gradually returned to normal. After two months of follow up, the patient is on dietary treatment and with a fasting glucose of 132 mg/dl. PMID- 11775347 TI - [Prader-Willi syndrome. Treatment with growth hormone in 2 cases]. AB - Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by the absence or abnormal inactivation of a critical region of the paternal chromosome 15. Clinical manifestations include marked hypotonia at birth, progressive obesity that starts during the second year of life, stunting, hypogonadism and some dysmorphic features. Some of the symptoms and signs can be explained by growth hormone (GH) deficiency. We report two females aged 12 and 13 years old with PWS. Both were very short and obese, showed blunted GH responses to provocative stimuli and had low plasma levels of Insulin Growth Factor-1 (IGF-1). They have been on GH treatment for more than two years, demonstrating a marked growth acceleration, reduction in their fat mass, improvement of their muscular strength and an increase in their IGF-1 levels. PMID- 11775348 TI - [Massive pericardial effusion and cardiac tamponade as the presentation form of hypothyroidism]. AB - We report a 43 years old female, admitted due to fatigability, asthenia and diffuse abdominal pain. On admission, obesity, slowness of thinking, bradycardia, distention of jugular veins and ascites were observed on physical examination. Laboratory showed undetectable thyroid hormone levels, a chest X ray showed bilateral pleural effusion and an enlarged heart. An echocardiography showed a massive pericardial effusion with collapse of the right atrium and dilatation of both caval veins. A pericardial tap was performed, draining 350 ml. Thyroid hormone substitution was started and after 12 months of follow up, the heart size decreased and a control echocardiogram showed a minimal pericardial effusion. PMID- 11775349 TI - [Cancer mortality in Chile: epidemiological considerations]. AB - Malignancies are the second most important cause of mortality in Chile, accounting for 21.8% of total deaths. In comparison with other causes, cancer mortality shows an upward trend with increasing mortality rates from 99 to 118 per 100.000 population in the period 1980-1998. The most important cancer locations are stomach, lung and prostate among men and gallbladder, stomach, breast and uterine cervix in women. According to present risks, the mean probability for a Chilean to die from cancer is 3.0% for stomach, 2.3% for prostate, 2.0% for lung, 1.7% for gallbladder, 1.6% for breast and 1.2% for uterine cervix cancer. Recent trends of cancer crude death rates are a matter of concern. During the period 1990-1998 a significant decrease of death rates was only noticed for uterine cervix cancers. On the other hand, important increases were observed for prostate, lung, gallbladder, colon and kidney cancers. If death rates are adjusted by age, an increased risk, not due to the population aging process, is noticed for prostate and to less extent for kidney, colon, skin and myeloma. The adjusted rates show a downward trend for uterine cervix, stomach, breast and esophagus cancer. Increasing cancer mortality is associated with diagnostic and therapeutic delays. Possible actions in screening programs are discussed. PMID- 11775351 TI - Non-traditional risk factors for atherosclerosis. AB - During the last 10 years, several "non-traditional" risk markers for atherosclerosis have been identified. Among them, new markers of lipoprotein metabolism (i.e. lipoprotein [a]), endothelial dysfunction (i.e. homocysteine), hemostasis (i.e. fibrinogen) and inflammation (i.e. C-reactive protein) have been linked to an excessive risk of cardiovascular disease. These factors should help the clinician to better identify individuals at risk of premature atherosclerotic disease and/or improve the predictive value of established risk factors for atherosclerosis. Finally, these factors are expected to improve the knowledge in the pathophysiology of cardiovascular diseases, and perhaps to impact future therapeutic decisions. In this review article, we will analyze the markers in which there are at least some evidence to support their acceptance as "non traditional risk factors" for atherosclerotic disease. PMID- 11775350 TI - [Docosahexaenoic acid (DHA) in fetal development and in infant nutrition]. AB - Docosahexanoic acid (C22:6, DHA) is a highly unsaturated omega-3 fatty acid that forms part of the central nervous and visual system structures. DHA is synthesized from its precursor, alfa-linolenic acid, that is also a omega-3 fatty acid and can be obtained from vegetable oils. Marine organisms, specially fish, are good nutritional sources of DHA and eicosapentanoic acid (EPA), another omega 3 fatty acid that has a role in vascular homeostasis. DHA increases membrane fluidity, improving neurogenesis, synaptogenesis and the activity of retinal photoreceptors. The fetus, specially during the last trimester of pregnancy, has high DHA requirements. It is provided by the mother, since fetal DHA synthesis is negligible in this stage of development. Breast feeding provides DHA to the child, but most replacement artificial formulas do not provide this fatty acid. At the present moment, many products for infant nutrition contain DHA. PMID- 11775352 TI - [In relation to Cleopatra and snake bites]. AB - Cleopatra VII, one of the last Egyptian sovereigns of the ptolomeic dynasty, is envisioned as a mythic figure, surrounded by intrigues and mystery. her mysterious death was caused, according to history, by a snake bite. This article shows some instances of great Cleopatra's life and the state of the art on snake venoms. Even at the present time, snake bites are a public health problem in Asia, Africa, Central and South America, causing more than 25,000 deaths every year. Most snake venoms have a protein structure and cause neurotoxic and hemolytic effects, altering coagulation and fibrinolysis. The mortality due to snake bites fluctuates between 1 and 22%. Specific treatment includes the use of specific antiserums with highly purified components. PMID- 11775353 TI - [Analysis of microcystins in cyanobacteria, water, shellfish and fish]. PMID- 11775354 TI - Structural determination of subsidiary colors in commercial Food Green No. 3 (fast green FCF, FD & C Green No. 3). AB - HPLC analysis revealed that eight subsidiary colors existed in commercial Food Green No. 3 (fast green FCF, FD & C Green No. 3). Among them, four subsidiary colors C, F, G, and H were isolated by using preparative HPLC and their structures were determined by MS and NMR. They were the disodium salt of 2-[[4-[N ethyl-N-(3- sulfophenylmethyl)amino]phenyl][4-[N-ethyl-N-(4- sulfophenylmethyl)amino]phenyl]methylio]-4-hydroxybenzenesulfonic acid (abbreviated as m,p-G-3), the sodium salt of 2-[[(4-N-ethylamino)phenyl][4-[N ethyl-N-(3- sulfophenylmethyl)amino]-phenyl]methylio]-4-hydroxybenzenesulfonic acid [abbreviated as HSBA-(EA) (m-EBASA)], the sodium salt of 2-[[(4-N diethylamino)phenyl][4-[N-ethyl-N-(3- sulfophenylmethyl)amino]phenyl]-methylio]-4 hydroxybenzenesulfonic acid [abbreviated as HSBA-(di-EA) (m-EBASA)], and the sodium salt of 2-[[4-[N-ethyl-N-(phenylmethyl)amino]phenyl][4-[N-ethyl-N-(3- sulfophenylmethyl)-amino]phenyl]methylio]-4-hydroxybenzenesulfonic acid [abbreviated as HSBA-(EBA)(m-EBASA)], respectively. HSBA-(di-EA) (m-EBASA) was a subsidiary color newly found in commercial Food Green No. 3. PMID- 11775356 TI - Identification of principal constituents in enzymatically hydrolyzed coix extract. AB - The structural elucidation of the main constituents in enzymatically hydrolyzed coix extract, a natural food preservative, was carried out. After peracetylation, five compounds, namely peracetylated forms of glucose, maltose, maltotriose, maltotetraose, and maltopentaose were isolated. The structures were determined by PFG HMQC and HMBC experiments. In addition, by using HPLC with an RI detector, the main components of this coix extract were identified as a mixture of oligosaccharides having one to seven glucose units coupled through alpha-(1-->4) linkages. Since this extract showed no antimicrobial activity, its preservative effect may be caused by its covering of the food surface, thereby blocking contact with air. PMID- 11775355 TI - [Analysis of glyphosate and its metabolite, aminomethylphosphonic acid, in agricultural products by HPLC]. AB - An analytical method for residues of the herbicide glyphosate [GLY: N (phosphonomethyl)-glycine] and its metabolite (AMPA: aminomethylphosphonic acid) in agricultural products is described. GLY and AMPA were extracted with water (soybeans extract was moreover treated with acetone), and purified by application to a dual mini-cartridge column (octadecyl-bonded silica gel and cation-exchange silica gel) system. GLY was derivatized with 9-fluorenylmethylchloroformate, and determined by HPLC with fluorescence detection. AMPA determination was performed by HPLC employing postcolumn fluorogenic labeling with o-phthalaldehyde mercaptoethanol. The detection limits for GLY and AMPA were 0.04 microgram/g (soybean: 0.08 microgram/g), and both recoveries from samples to which the compounds were added at the 0.2 microgram/g level (soybean: 1.0 microgram/g) were more than 65%. PMID- 11775357 TI - [Residual chemicals in silicone rubber products for food contact use]. AB - The residues of additives and other chemicals in 23 kinds of silicone rubber products for food contact use, including nipples, packing and spatulas, were investigated by GC/MS. The packing and spatulas contained 80-480 micrograms/g of BHT, 60-5,830 micrograms/g of di(2-ethylhexyl) phthalate (DEHP), and 60-80 micrograms/g of dibutyl phthalate, while the nipples contained no additives. All of the samples contained 15 to 20 peaks of polydimethylcyclosiloxanes. Dodecamethylcyclohexasiloxane (D6) to tetratriacomethylcycloheptadecasiloxane (D17) were confirmed, and other larger siloxanes up to pentacontamethylcyclopentacosasiloxane (D25) were estimated. A rough estimate of the total cyclosiloxane content was 3,310-14,690 micrograms/g. They might be mainly unreacted materials or by-products, and some of them might be additives. Based on the migration test, no chemicals were released into 20% ethanol at 60 degrees C for 30 min, though DEHP and the polydimethylcyclosiloxanes were released into n-heptane at 25 degrees C for 60 min. PMID- 11775358 TI - [Migrants from disposable gloves and residual acrylonitrile]. AB - Disposable gloves made from polyvinyl chloride with and without di(2-ethylhexyl) phthalate (PVC-DEHP, PVC-NP), polyethylene (PE), natural rubber (NR) and nitrile butadiene rubber (NBR) were investigated with respect to evaporation residue, migrated metals, migrants and residual acrylonitrile. The evaporation residue found in n-heptane was 870-1,300 ppm from PVC-DEHP and PVC-NP, which was due to the plasticizers. Most of the PE gloves had low evaporation residue levels and migrants, except for the glove designated as antibacterial, which released copper and zinc into 4% acetic acid. For the NR and NBR gloves, the evaporation residue found in 4% acetic acid was 29-180 ppm. They also released over 10 ppm of calcium and 6 ppm of zinc into 4% acetic acid, and 1.68-8.37 ppm of zinc di ethyldithiocarbamate and zinc di-n-butyldithiocarbamate used as vulcanization accelerators into n-heptane. The acrylonitrile content was 0.40-0.94 ppm in NBR gloves. PMID- 11775359 TI - [Determination of sulfite residues in foods by using the modified rankine apparatus and HPLC]. AB - A method for measuring sulfite residues in foods by using the modified Rankine apparatus and HPLC was developed. Sulfites released from foods by bubbling of nitrogen gas and heating for 15 minutes with an electric burner weRe absorbed in 1% triethanolamine solution and detected as sulfite ion by HPLC with a UV detector at 240 nm, using an anion exchange column, IonPac AS9-SC, with 1.8 mmol/L sodium carbonate-1.7 mmol/L sodium hydrogen carbonate solution as the mobile phase. The recoveries of sulfites added to 3 kinds of foods were 98-102%, and the determination limit was 0.001 g/kg. The sulfite values in various kinds of foods determined by the proposed HPLC method were consistent with those obtained by the alkaline titration method and the colorimetric method. PMID- 11775360 TI - [Survey of residual antibiotic agents in cultured fish and shellfish]. AB - A survey of residual antibiotic agents in cultured fish and shellfish purchased from the Tokyo Central Market was carried out. Out of 240 samples tested, OTC was detected in 14 samples which consisted of flatfish, yellowtail, seriola and eel. Synthetic antibiotic agents were not detected. The highest level of OTC was 0.36 microgram/g in skin of flatfish. In the case of flatfish, the concentration of OTC was highest in skin, followed by liver, then muscle. OTC was detected in livers of all yellowtail, seriola and eel, and the concentration was higher than that in muscle or skin. PMID- 11775361 TI - Effects of cooking on concentrations of polychlorinated dibenzo-p-dioxins and related compounds in green leafy vegetable 'Komatsuna'. AB - The effects of ordinary household cooking processes on concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) (dioxins) were investigated in 'komatsuna', a green leafy vegetable popular in Japan. The concentrations of dioxins were compared using isomer-specific analyses of both uncooked and cooked edible parts of the plant. The mean total 2,3,7,8-chlorine substituted PCDD and PCDF concentrations were reduced from 46.53 pg/g and 0.714 pg/g to 8.301 pg/g and 0.210 pg/g by washing with tap water, and further reduced to 6.054 pg/g and 0.148 pg/g by subsequent boiling, respectively. The cooking processes markedly decreased the concentrations of PCDD/Fs, while having little effect on those of dioxin-like PCBs. The mean total concentration as 2,3,7,8-tetraCDD equivalents (TEQ) was reduced from 0.058 pgTEQ/g to 0.026 pgTEQ/g by washing with tap water and further reduced to 0.019 pgTEQ/g by subsequent boiling. These results suggest that ordinary cooking processes provide a means of reducing the level of dioxins in green leafy vegetables. PMID- 11775362 TI - [Plastics used for kitchen utensils and food packages (characteristic of polymer and discriminating method)]. PMID- 11775363 TI - [Human body burden and intake of PCDDs, PCDFs and Co-PCBs in breast fed infants and adults of Japan]. PMID- 11775364 TI - [Occurrence, toxic effects and sources of brominated dioxins in environmental samples]. PMID- 11775365 TI - [Nutrient function and health claims on foods in Japan: food with health claims]. PMID- 11775366 TI - The fallout from September 11. How is health care responding to a new reality? PMID- 11775367 TI - Doctors in management. On the side walk. AB - The latest NHS reorganisation proposes that doctors in trusts should be given more managerial responsibility. Attempts to Involve doctors in NHS management over the last 10 years have not been wholly successful. The constant reorganisation of the NHS hinders the integration of clinicians in management. PMID- 11775368 TI - Doctors in management. A question of culture. PMID- 11775369 TI - Doctors in management. Career view mirror. AB - A survey of doctors and managers found agreement that management training should be given at various stages of a doctor's career. Managers felt strongly that doctors should receive management training in groups with other staff. Doctors believed clinical budgets should be under doctors' control, but managers were opposed to this. The results suggested that a 'them and us' culture persists between managers and doctors in the NHS. PMID- 11775370 TI - Nursing directors. Great barrier reach. AB - A survey of nurse directors showed that only half of those who had applied for chief executive posts had been shortlisted. As many as 70 per cent of respondents said that nurse directors are prevented from becoming chief executives because they are stigmatized. Gender was identified as a barrier by 43 per cent of respondents. PMID- 11775371 TI - Nursing directors. Up they go. PMID- 11775372 TI - Open space. The status we're in. PMID- 11775374 TI - [Occupational asthma or asthma aggravated by work and aptitude]. PMID- 11775373 TI - [Menopause and work: emergent problems in capacity assessment]. PMID- 11775375 TI - [Assessment of specific work capacity and occupational reinsertion of a worker with cardiopathy: a methodological proposal]. PMID- 11775376 TI - [Work capacity of an epileptic patient receiving pharmacological therapy]. PMID- 11775377 TI - [Capacity assessment of workers exposed to radiofrequencies]. PMID- 11775378 TI - [Assessment of work capacity concerning specific tasks and epileptic disease]. PMID- 11775379 TI - [Proposal of behavior in the formulation of specific capacity evaluation for health personnel concerning risks due to hepatotropic virus]. PMID- 11775380 TI - [Special aspects of capacity assessment: the cardiologic evaluation]. PMID- 11775381 TI - [Observations on the concept of capacity. Present-day topic on the threshold of luminous 2000. Old antique world and current perspectives]. PMID- 11775382 TI - [Formation of the medical board of evaluation and commission of reassessment concerning work capacity of first-time employed subjects]. PMID- 11775383 TI - Profiles in leadership. James D Funnell, M.D. PMID- 11775384 TI - Physician perceptions regarding competence of obstetrical providers and attitudes about other issues in obstetrical care. AB - BACKGROUND: Access to obstetrical care in the United States is unevenly distributed and is limited by provider availability, geography, and finances. Obstetrical care is provided by three distinct groups: obstetricians, family physicians, and certified nurse midwives (CNMs). Outcomes among these groups have not been shown to differ, but the attitudes and perceptions of these groups may impact access to obstetrical care. We examined physicians' perceptions regarding competence of obstetrical providers for low- and high-risk care and attitudes regarding CNMs and malpractice insurance costs. METHODS: We mailed a survey containing twenty value-neutral questions on competency, attitudes, and demographics to a randomized list of 3,000 OB/GYNs and 3,000 FPs obtained from the American Medical Association. Physicians surveyed included obstetricians (OB/GYNs), obstetricians specializing in high-risk (HROBs), family physicians who include obstetrics in their practice (FPOBs), and family physicians who do not do obstetrics (FPs). RESULTS: The response rate was 14.5 percent. All respondent types expressed a high degree of confidence in OB/GYNs to provide low-risk obstetrical care. FPOBs were not perceived to be as competent to provide the same care, but FPOBs have more confidence in their ability to provide low-risk obstetrical care than OB/GYNs have (71.4% versus 43.8%, P = .0001). Attitudes differed among the physicians about malpractice insurance fees paid by OB/GYNs and FPOBs. OB/GYNs strongly supported a similar fee schedule for these two groups and FPs supported differential rates (P = .001). CNMs were generally perceived as competent and were thought to warrant hospital privileges for vaginal deliveries. CONCLUSIONS: Physicians view their own and others' obstetrical competence and outcomes differently, but not necessarily accurately. Malpractice rates are not perceived by OB/GYNs as fair. Specialty societies need to promote cooperation and enhance education of all providers of obstetrics. PMID- 11775385 TI - Non-surgical therapy of primary hyperparathyroidism. AB - BACKGROUND: Primary hyperparathyroidism is a commonly encountered illness that can usually be treated successfully with surgery. However, non-surgical ablation by either infusion of contrast media via angiography or percutaneous injection of ethanol has been reported from a few medical centers. METHODS: All patients undergoing non-surgical treatment of primary hyperthyroidism at the University of Oklahoma Health Sciences Center were identified and their records reviewed. RESULTS: We have used non-surgical techniques to treat three patients with primary hyperparathyroidism. The patients were considered poor surgical candidates or had persistent hypercalcemia after neck exploration. Hypercalcemia was improved or cured in each of the patients without recurrence. CONCLUSIONS: Our application of these techniques indicates that centers without extensive experience can successfully employ angiographic or ethanol ablation of parathyroid adenomas. PMID- 11775386 TI - Preventive medicine and the Oklahoma City Veterans' Affairs Medical Center. AB - Beginning in 1996, the Oklahoma City VA Medical Center has implemented a preventive medicine program. This program includes such steps as tobacco and alcohol counseling, control of chronic illness and appropriate reminders and record-keeping. The results are promising. PMID- 11775387 TI - HIPAA privacy regulations: standards, guidance, and "reasonable" efforts. PMID- 11775388 TI - Allergy and asthma prevention: the cup half full. AB - Lack of an effective approach to atopic disease prevention is implicit in the global rise in asthma and allergy prevalence over the last 10-20 years. Indeed, asthma appears to be the most common chronic disease of childhood, allergies seem more common than not, and recent evidence suggests that this atopic disease burden is influencing adult prevalence of these conditions as well. Thus, the time seems right for prevention. Considering our current understanding of asthma and allergy pathogenesis, numerous strategies of atopic disease prevention can be envisioned. These strategies can be organized as follows: (1) allergen avoidance; (2) anti-inflammatory pharmacotherapy; (3) inhibition of Th2-type immune development by Th1-type cytokine induction; and (4) dietary and environmental approaches to atopic disease prevention. PMID- 11775389 TI - Endotoxin: friend or foe? AB - Endotoxin in our living environment has been of increasing interest to our global community of allergists. Initially and largely studied for its capacity to mediate septic shock (and earning its "-toxin" suffix), we have since come to understand that endotoxin in the dust of many occupational settings also is an occult respiratory culprit, inducing airflow obstruction and aggravating asthma and allergies. More recently, environmental endotoxin has been implicated as a microbial exposure in early childhood that may have an atopy-protective effect by augmenting early Th1-type immune development. Although seemingly paradoxical, endotoxin's dual nature ultimately may serve to enlighten our understanding of how such bioactive exposures can interact with and guide our immune systems in both health and disease. PMID- 11775390 TI - Hidden factors in asthma. AB - The importance of discovering and treating hidden factors that exacerbate asthma as specified in component 2 of the 1997 National Heart Lung and Blood Institute (NHLBI) expert panel report guidelines has been overshadowed by a disproportionate emphasis on component 3 (pharmacologic therapy). This has resulted in disease management models that consist of a two-step classification treatment system in which little regard is given to the evaluation of underlying contributing factors. In addition to the identification of environmental allergens, an aggressive evaluation of other potential factors that may contribute to asthma is essential to optimal, efficient, and cost-effective asthma care. These factors include sinusitis, allergic rhinitis, and gastroesophageal reflux. Diagnostic testing for sinusitis and/or gastroesophageal reflux is warranted even in the absence of suggestive signs or symptoms for many patients with asthma classified in the moderate and severe ranges by NHLBI guidelines. A disease management algorithm for gastroesophageal reflux disease in the patient with asthma is proposed. PMID- 11775391 TI - Theophylline revisited. AB - Theophylline was first isolated in 1888 and remains the most commonly used medication worldwide for the treatment of asthma. It decreases the need for asthma rescue medications by people who have asthma and is an effective steroid sparing agent for patients who tolerate it. Recently, investigators have shown that theophylline decreases airway inflammation, accelerates eosinophil apoptosis, and decreases recruitment of lymphocytes and neutrophils to the lungs at low doses. It is classified as a phosphodiesterase (PDE) inhibitor, but its therapeutic mechanism of action remains undetermined. Theophylline should be reevaluated as a long-term medication for the treatment of asthma because of its ease of use, low cost, and recent evidence of its anti-inflammatory actions. PMID- 11775392 TI - Update on the development and use of viral and bacterial vaccines for the prevention of acute otitis media. AB - Acute otitis media (AOM) is the most frequent diagnosis in physician offices among children 1-4 years of age. Viruses that cause upper respiratory tract infections (i.e., respiratory syncytial virus [RSV], influenza virus, parainfluenza virus [PIV], and others) play an important role in the development of AOM. Prevention of infections with these viral pathogens likely would reduce the incidence of AOM. In three previous studies, influenza virus vaccines showed 30-36% efficacy against the development of AOM. Vaccines to prevent infections with RSV and PIV type 3 are undergoing clinical testing at this time. The three major bacterial pathogens causing AOM are Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis. Pneumococcal conjugate vaccine, licensed in the United States in 2000, was shown in two pivotal trials to reduce the incidence of all causes of AOM by 6%, pneumococcal AOM by 34%, and pneumococcal AOM caused by serotypes contained in the vaccine by 57%. Currently, vaccines against NTHi and M. catarrhalis are under development. PMID- 11775393 TI - Safety of budesonide inhalation suspension (Pulmicort Respules) after up to 52 weeks of treatment in infants and young children with persistent asthma. AB - Three open-label extension trials evaluated the safety of budesonide inhalation suspension (BIS; Pulmicort Respules) in 670 children (8 months-9 years of age) with mild-to-severe persistent asthma. Patients were randomized to receive either BIS or conventional asthma therapy (CAT) for 52 weeks. The percentage of patients who discontinued because of clinical adverse events was low and similar among the CAT (0.4%) and BIS (0.7%) groups. After adjusting for length of time in the studies, there were no clinically relevant differences between the BIS and CAT groups in the type, incidence, or intensity of adverse events; vital signs or physical examination outcomes; or changes in clinical laboratory evaluations or oral fungal cultures. PMID- 11775394 TI - Does using a mouthwash instead of water improve the oropharyngeal removal of inhaled flovent (fluticasone propionate)? AB - Rinsing the mouth with water is recommended to remove inhaled corticosteroid (ICS) deposited on the oropharyngeal mucosa. Given the lipophilicity of fluticasone propionate (FP), an ethanol-based mouthwash was hypothesized to be superior to water. This study's purpose was to compare the effectiveness of water versus Listerine (Warner Lambert, Lititz, PA) in removing FP from the oropharyngeal mucosa. Asthma patients were randomly assigned water or a Listerine rinsing vehicle. A 440-microgram dose of FP was inhaled. After the second puff, patients rinsed for 30 seconds with 20 mL of the assigned agent and then repeated the process, spitting each "wash" into the same cup. At visit 2, patients used the alternate vehicle and repeated the procedure. Samples were frozen until analyzed using liquid chromatography/mass spectrophotometry (lower limit of detection 0.067 microgram/mL). Thirty-six patients (mean age, 44 years; 66% female) participated. Mean inhaler technique score was 11.3 (scale of 1-12). Eighty-three percent used the closed-mouth technique. The mean concentration of FP removed by Listerine was not statistically different than that removed by water, 1.67 micrograms/mL (range, 0.067-4.195 micrograms/mL) and 1.42 micrograms/mL (range, 0.067-5.107 micrograms/mL), respectively, and the total milliliter returned was assumed to be 40 mL. Regression analysis using sex, age, and inhaler technique showed no statistical relationship with the amount of FP removed. Therefore, Listerine was not more effective than water in removing FP from the oropharyngeal mucosa (p = 0.53). Thus, water is an adequate rinsing vehicle for removal of ICS deposited on the oropharyngeal mucosa. Other factors besides the rinsing vehicle are strong factors in determining the amount of drug removed. PMID- 11775395 TI - High dose inhaled fluticasone propionate improves FEV1 and results in reduction of oral glucocorticoid dose in glucocorticoid-dependent children with severe asthma. AB - A retrospective chart review was performed on eight pediatric patients with glucocorticoid (GC)-dependent asthma who had been switched to fluticasone propionate (FP). A significant increase was noted in average forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75) at 6 and 12 months. Significant reductions were noted in the oral GC dose at 6 and 12 months with a reduction at 12 months of almost 16.5 mg/day or 65% of the initial oral GC dose. This study suggests that high-dose FP use in children with oral GC dependent asthma has oral GC sparing effects while improving FEV1 and FEF25-75. PMID- 11775396 TI - Aspirin treatment of patients with aspirin intolerance, asthma, and nasal polyps. AB - Patients with the triad of aspirin (ASA) intolerance, asthma, and nasal polyps present a clinical challenge for the allergist because their polyps generally are refractory to traditional treatments and their asthmatic symptoms may become more difficult to control with time. These patients can be desensitized and treated with ASA with subsequent improvement in their nasal and respiratory symptoms. This article describes one such individual and briefly reviews the literature regarding this triad. The diagnosis of ASA intolerance, mechanistic studies, a desensitization protocol, and new therapies are reviewed. PMID- 11775397 TI - Asthma among the famous. Patrick O'Brian (1914-2000) British author. PMID- 11775398 TI - Introduction: patient preference of inhaled nasal corticosteroids. PMID- 11775399 TI - Patient preferences and satisfaction with prescribed nasal steroids for allergic rhinitis. AB - A telephone survey of 503 patients with seasonal and perennial allergic rhinitis was performed to assess satisfaction with their nasal steroid therapy and their reasons for preferences for particular products. Product attributes such as efficacy and various sensory features (e.g., nasal irritation, odor, and taste) were evaluated. Although patients generally are satisfied with their nasal steroid preparations, they do show clear preferences for the sensory attributes of different products. Patients are willing to switch on their physicians' recommendations and clearly prefer products with no odor and no taste. PMID- 11775400 TI - Physician prescribing practices: the role of patient preference in the selection of nasal steroids. AB - A telephone survey of 100 primary care physicians was performed to assess the awareness of the influence patient preference, patient satisfaction, and other factors have on the selection of nasal steroids for the treatment of allergic rhinitis. Results indicated that physicians believe drug efficacy is the primary reason why one product is chosen over another, while sensory attributes are the next most important criteria for distinguishing among products. Physicians agree that patients would prefer a preparation that has no odor or aftertaste and that patients are willing to switch products if their physicians recommend that they do so. PMID- 11775401 TI - Comparisons and contrasts: patients and physician surveys. PMID- 11775402 TI - Consensus and conclusions: patient preference of inhaled nasal corticosteroids. PMID- 11775404 TI - Perspectives. Recession to bring minimal Medicaid cuts, impetus to reform? PMID- 11775403 TI - Efficacy, safety, and patient preference of inhaled nasal corticosteroids: a review of pertinent published data. AB - Most clinical studies of inhaled nasal corticosteroids have established comparable safety and efficacy; therefore, there remains little to distinguish the various products from each other in the treatment of allergic rhinitis. However, patient preference is recognized increasingly as an important factor in selecting appropriate treatment. This review discusses the different methodologies that have been used to measure patient preference for intranasal corticosteroids. Patient questionnaires and other instruments for assessment that are used to measure such preferences are discussed as well as several different study designs. Now, the challenge is to implement more studies that show the reliability and consistency of instruments used to assess patient preference. PMID- 11775405 TI - [We, the Italian physicians, and statins]. AB - After marketing withdrawal of cerivastatin physicians asked several questions regarding the efficacy and safety of statins, the real risk of myopathy, the compared efficacy of all the statins, the reasons why severe adverse events could happen despite several long-term randomized controlled trials, the approval from regulatory agencies. This is the position statement of the Italian Federation of Cardiology. Synthetic answers to previous questions are addressed and few suggestions to avoid that similar conditions should occur again. Finally, the appropriate prescription of statins is recommended. PMID- 11775406 TI - [Non-invasive evaluation of the endothelial function using high-resolution B-mode ultrasonography]. AB - The vascular endothelium has a central role in regulating vasomotor tone, smooth muscle cell proliferation, platelet and leukocyte adhesion to the arterial wall, thrombosis and fibrinolysis. Disturbances of these endothelial functions have been suggested to be important in the early and advanced phases of atherosclerosis. The development of a simple, valid ultrasound-based method allowed to non-invasively evaluate endothelial function in a large number of individuals with traditional and non-traditional cardiovascular risk factors. The ultrasound technique measures changes in brachial artery diameter in response to an increase in blood flow (reactive hyperemia) and thus in shear stress, which causes endothelium-dependent dilation. This methodology is not yet perfect. The critical issues today involve the definition of "normal values", and standardized scanning and reading protocols to reduce variability. PMID- 11775407 TI - [Antihypertensive therapy in the elderly: results of large trials]. AB - The aim of this review was to evaluate if antihypertensive treatment in elderly hypertensive patients is able to lower the incidence of cardiovascular events when compared to hypertensive controls who received placebo. All trials agree in that the greater blood pressure reduction in hypertensive patients randomized to active treatment is associated with a minor incidence of cerebrovascular, cardiac and all cardiovascular events in comparison to placebo-treated control groups. Therefore the chronic antihypertensive treatment makes more good than bad. All antihypertensive agents have been used for the treatment of arterial hypertension in the elderly and all have shown a good efficacy and tolerability, even if, as in the adult hypertensives, the combination of two or more agents is necessary in the great majority of hypertensive patients to reach the target blood pressure. Because life expectancy is progressively longer and the prevalence of hypertension, in particular isolated systolic hypertension, is age-dependent, it is clinically relevant to investigate if there is an upper limit for the benefit of antihypertensive therapy. The results so far available suggest a benefit up to the age of 80 years, while an ongoing study is aimed at evaluating the benefit of antihypertensive therapy in patients > 80 years. Finally, according to our personal point of view, there are sufficient data to sustain the indication of a diastolic blood pressure reduction between 80 and 90 mmHg, while the indication to a reduction in systolic blood pressure below 140 mmHg is less strong and supported. PMID- 11775408 TI - [Diabetes and arterial hypertension]. AB - Type II diabetes and hypertension are two pathologies which are frequently associated in adults, especially in developed countries. All the more so when patients are also obese: obesity is today, and will be in the next future, a true epidemic in these countries. These three pathologies imply a risk for cardiovascular complications much higher than that due to an isolated arterial hypertension. This increased risk is probably due to many factors: hyperglycemia, a dismetabolic syndrome (hyperlipemia, hyperuricemia, thrombophilia, altered Na(+)-H+ membrane exchanges = syndrome X) and hyperinsulinemia which favor atherosclerosis and clinical events. Consequently non-pharmacological and aggressive pharmacological therapy is necessary. Even if the trials done in the last years are questionable and not totally convincing, all researchers agree that lowering blood pressure to normality is the best way to improve prognosis of these patients. Usually for this purpose we need a therapy with more than one drug. Among the antihypertensive drugs, ACE-inhibitors (and perhaps also angiotensin receptor blockers) are preferred, especially in those hypertensives with diabetes who have also microalbuminuria or a frank proteinuria. PMID- 11775409 TI - [Fascicular ventricular tachycardia]. AB - Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site. PMID- 11775410 TI - [Pulmonary embolism: the past and . . . the future]. AB - The history of pulmonary embolism cannot be reconstructed reliably beyond the last two centuries, starting with the Napoleon's times by the works of Laennec. We owe the first pathological and clinical descriptions to European scientists, especially French, German and Italian. Interestingly, some ideas regarding pathophysiology and even hemodynamics can be found in papers published as early as the end of the 19th century. Of note, the strong relationship between venous thrombosis and pulmonary embolism, suspected already in the middle of the 19th century, resulted later in a new clinical entity named venous thromboembolic disease. Only just before the second world war "modern" diagnostic tests entered into the clinical arena. Beginning with electrocardiography and X-ray techniques including pulmonary angiography, the progress in the field of imaging continued with lung scan, echocardiography, computed tomography, and finally still largely unexplored ultra-fast magnetic resonance imaging techniques: despite this technological development the correct diagnosis of pulmonary embolism in daily practice remains an important challenge. This is due to the lack of a single test which would combine high diagnostic power, round-the-clock availability and reasonably low cost. Though thrombotic origin of pulmonary embolism was well documented for almost two centuries, anticoagulation as a treatment for venous thromboembolism dates back much less than a century and thrombolysis was initiated only 30 years ago. What is even worse, those 30 years were not enough for us to identify clear-cut criteria in the selection between thrombolysis and anticoagulation in individual patients. Not to speak about the problem regarding optimal duration of secondary prophylaxis after a thromboembolic episode. Still how long shall we be debating about the same problems at the bed of our patients with venous thromboembolism? Or maybe the near future will bring completely new answers to our old questions? What type of case report related to pulmonary embolism will have the chance to be accepted for publication in the Italian Heart Journal in the year ... 2050? Future will show? But only if we help it.... PMID- 11775411 TI - [Interaction between congestive heart failure and diabetes mellitus: critical review of the literature]. AB - It is known from the Framingham Heart Study that there is a relationship between congestive heart failure and diabetes mellitus. Diabetes can cause myocyte hypertrophy, interstitial fibrosis, impaired myocardial blood flow, increased turnover of free fatty acids, leading to the development of cardiomyopathy. On the other hand, heart failure increases catecholamine plasma levels and it may cause insulin resistance, leading to the development of diabetes. We report and discuss data from the literature: ACE-inhibitors do not alter glucose metabolism, non selective beta-blockers increase insulin resistance, while beta-blockers with vasodilating properties do not seem to alter insulin sensitivity, and high doses of diuretics seem to have a negative effect on glycemic parameters. Since diabetes has a high prevalence among patients with heart failure, it is clinically relevant to monitor glycemic parameters in such patients and also to evaluate changes in the therapy. PMID- 11775412 TI - [The VIP Project: prevalence of risk factors for ischemic cardiopathy in an area of Campania]. AB - BACKGROUND: The purpose of the VIP Project was to verify the distribution of coronary risk factors and the treatment of high risk subjects among the population in an area of Irno Valley in South Italy. METHODS: In this study, people aged 25-74 years were randomly enrolled from the electoral register and were then visited and subjected to blood venous drawing. The project consisted of three phases: identification and classification of high risk subjects; treatment; follow-up (after 5 and 10 years). In this paper all data gathered during the first control (1998-1999) are reported. Data refer to 1200 subjects (600 men and 600 women). RESULTS: The prevalences of risk factors were the following: hypercholesterolemia (serum cholesterol > or = 240 mg/dl): men 13.6%, women 18.6%; hypertriglyceridemia (serum triglycerides > or = 170 mg/dl): men 33.6%, women 17.9%; hyperglycemia (blood glucose > or = 126 mg/dl): men 11.2%, women 10.4%. The mean levels of systolic blood pressure were: men 132.6 mmHg and women 132.15 mmHg; diastolic blood pressure: men 83.97 mmHg and women 82.86 mmHg. Male subjects with hypertension (> 159/94 mmHg) were 29.1% while female subjects were 28.9%. The prevalence of smokers was 43% for men and 21.7% for women. CONCLUSIONS: Data show some important aspects (especially when they are compared with Montecorvino Rovella Project, an epidemiologic research on cardiovascular risk factors also carried out in the Province of Salerno in 1988-1989): there is a reduction of cholesterolemia and of prevalence of hypercholesterolemia; smokers are decreasing but there is an increase in female smokers; doctors treat men more efficaciously than women; in the female population, aged 45 to 54 years, there is an increase, in unacceptable proportions, in cardiovascular risk factors. PMID- 11775413 TI - [Cor triatriatum dextrum resulting from the persistence of embryonic remnants of the right valve of the sinus venosus: prevalence and echocardiographic aspects in a large consecutive non-selected patient population]. AB - BACKGROUND: Cor triatriatum destrum is a rare congenital malformation, usually associated with complex right heart abnormalities, characterized by a membrane that divides the right atrium into two chambers. It is considered the result of the incomplete and abnormal regression of the embryonic right valve of the sinus venosus. When the valve regresses the cephalic portion forms the crista terminalis and the caudal portion develops into the Eustachian and Thebesian valve. With an incomplete regression, a fenestrated or an unfenestrated membrane may persist in the right atrium. We describe the clinical and echocardiographic characteristics of this type of remnants in the right atrium. METHODS: In a 4 month period, 1728 transthoracic two-dimensional and Doppler echocardiographic studies were consecutively performed. RESULTS: Twenty-seven patients (16 males, 11 females, mean age 55 +/- 21 years, range 1-87 years) were occasionally recognized to be affected by a membrane inside the right atrial cavity. On the basis of its echocardiographic appearance (a membranous structure connecting the orifice of the inferior vena cava to the atrial septum with evident fenestration in 74% of cases), absence of associated congenital abnormalities (92.5% of cases), interatrial shunt or abnormal flow pattern of venous systemic return, a diagnosis of a normal benign anatomic variant of sinus venous remnants (similar to the so-called "Chiari's network") could be made in every case. CONCLUSIONS: The incomplete regression of the embryonic right valve of the sinus venosus may leave a fenestrated or an unfenestrated membrane in the right atrium that should be considered a normal benign variant of the so-called "Chiari's network". PMID- 11775414 TI - [Surgical repair of degenerative atrial valve: long-term results]. AB - BACKGROUND: The advantages of mitral valve repair in myxomatous regurgitation are well established. The durability of this reconstructive procedure is variable. The timing of operation is the surgeon dilemma. The aim of this study was to evaluate the early and long-term results of mitral valve repair in myxomatous regurgitation. METHODS: Between January 1990 and December 1997, 121 patients (77 males, 44 females) were operated on for myxomatous regurgitation with mitral valve repair. The surgical indication was based on the severity of mitral valve insufficiency and left ventricular dysfunction rather than the functional class. The surgical techniques were: quadrangular resection of the posterior mitral leaflet and sliding suture, triangular resection of the anterior mitral leaflet, chordal transposition and neo-chords suture, prosthetic ring (Carpentier-Edwards and Biflex rings) suture. RESULTS: There was 1 hospital death (0.8%). Long-term follow-up between 6 months and 107 months was available in 100% surviving patients. There were 6 late deaths, 3 for cardiac and 3 for non-cardiac events. CONCLUSIONS: Valve repair in mitral regurgitation caused by myxomatous disease provides excellent survival results at 51 months. Adverse outcome occurs in patients with preoperative left ventricular dysfunction, even if asymptomatic. PMID- 11775415 TI - [Asymptomatic severe aortic stenosis: always surgical treatment? The opinion of the surgeon]. AB - Prophylactic valve replacement in asymptomatic patients with severe aortic stenosis is controversial. Most authors consider that patients could be managed without surgery until symptoms develop. The incidence of sudden death in patients without symptoms is low, < 1%/year and valve replacement is complicated by an operative mortality up to 5 and 1-2% of incidence of valve-related major events. Early surgical approach is suggested by several observations. The first one is the unpredictable risk of myocardial fibrosis after long standing left ventricular hypertrophy and pressure overload, with associated systolic and diastolic dysfunction. Left ventricular impairment can persist after valve replacement influencing exercise capacity and survival in selected patients. On the other hand, major improvement in myocardial protection techniques, intraoperative monitoring with transesophageal echocardiography, prosthetic design (stentless, supra-annular), all have reduced in-hospital mortality and morbidity. More precise recommendations can be made according to an improved characterization of the patients from fast to slow evolution, according to age, type of aortic stenosis, degree of calcification, changes in transaortic gradients over time, tolerance to exercise test and response of aortic valve area to dobutamine. In patients with high risk of progression (severely calcified valve, Doppler velocity > 4 m/s, rapidly increasing with time), indirect evidence of myocardial fibrosis (excessive left ventricular hypertrophy, systolic or diastolic dysfunction), and need of myocardial revascularization, an early surgical approach should be considered. PMID- 11775416 TI - [Asymptomatic severe aortic stenosis: always surgical treatment? The opinion of the cardiologist]. AB - Aortic valve replacement is the effective treatment for symptomatic aortic stenosis. On the other hand, there is some lack of agreement about the optimal timing of surgery in asymptomatic patients. We support the opinion that survival of asymptomatic patients with aortic stenosis is excellent without surgery. At present even if surgical mortality can be minimized, the combined risk of surgery and late complications of a prosthesis exceed the possibility of preventing sudden death and prolonging survival in all asymptomatic patients. It may be useful to identify asymptomatic patients at high risk of sudden death, with abnormal response to exercise, or with left ventricular systolic dysfunction or excessive hypertrophy for early surgery. In the future, when surgical techniques and techniques for the preservation of biological valve are improved, or the risk of thromboembolism associated with mechanical prostheses is reduced, and the freshly harvested matched homografts become more widely available, the indications for aortic valve replacement will be extended to patients with hemodynamically severe aortic valve disease, in the absence of symptoms or left ventricular dysfunction. PMID- 11775417 TI - [Acute myocardial infarct in HIV-positive patients in treatment with protease inhibitors]. AB - We report the case of a 40-year-old HIV-positive man, undergoing three-drug antiretroviral therapy for 2 years that included a protease inhibitor (ritonavir). The patient was admitted to our Coronary Care Unit with an acute anterior myocardial infarction. He smoked 20 cigarettes/day and had a family history of hypertension. At the time of hospitalization, triglyceride levels were found to be high (290 mg/dl). Metabolic alterations associated with the prolonged use of protease inhibitors, such as insulin resistance, dyslipidemia and lipodystrophy, have recently been described. This side effect may lead to premature coronary artery disease. Therefore it is mandatory to be aware that treatment with protease inhibitors in HIV-positive patients, despite survival prolongation and lowering of AIDS complications, may accelerate atherosclerosis and precipitate acute coronary events, especially in patients with pre-existing cardiovascular risk factors. PMID- 11775418 TI - [Late-appearing cholestatic icterus after a month of treatment with ticlopidine]. AB - A 65-year-old man was submitted to coronary angioplasty and stent implantation for stable angina. The treatment included a 30-day therapy with ticlopidine (in addition to aspirin, metoprolol, ramipril, amlodipine and nitrates). One month after ticlopidine withdrawal a progressive cholestatic jaundice took place. Viral, immunogenic as well as nutritional causes were ruled out. The abdominal echography disclosed a normal biliary tree and the liver biopsy showed a centrolobular cholestasis pattern. Drug-induced cholestatic reaction was diagnosed and attributed to ticlopidine. There was a progressive improvement in clinical and laboratory findings 4 months after steroid treatment. The clinical picture was normalized after 6 months. When considering the option ticlopidine, even for a short time after coronary angioplasty, the possibility of drug-induced hepatotoxicity should be kept in mind. Consequently, markers of liver toxicity should be monitored carefully. PMID- 11775419 TI - [Long-term survival after ablation of atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation]. PMID- 11775421 TI - [Evidence that human cardiac myocytes divide after myocardial infarct]. PMID- 11775420 TI - [Effect of carvedilol on outcome after myocardial infarction in patients with left ventricular dysfunction: the CAPRICORN randomized trial]. PMID- 11775422 TI - [Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure]. PMID- 11775423 TI - [Medicine in art still arises our curiosity]. PMID- 11775424 TI - NYU downtown hospital workers: unsung heroes of the 9/11 disaster. PMID- 11775425 TI - Hospital's community policing program helps win Lindbergh Bell Award. PMID- 11775426 TI - An interview with: Michael Hugyo on workplace violence: threat assessment toolbox. PMID- 11775427 TI - Concern about anthrax: protocols for mailrooms. PMID- 11775428 TI - Dealing with the continuing challenges of natural disasters. AB - Tropical Storm Allison--which struck the Texas and Louisiana coasts in June 2000- killed 22 people, flooded more than 27,000 homes, and caused an estimated $2 billion in property damage in the Houston area alone. Among the hardest hit were some 12 hospitals in the Texas Medical Center, south of downtown Houston, the world's largest medical facility, which all experienced flooding and reduction of services to various degrees. (The medical complex of 42 member institutions also includes numerous academic buildings and research laboratories where nearly 35,000 lab animals drowned.) Two of the hospitals were forced to evacuate all patients and close after losing emergency power. Sixteen patients died at medical center facilities during the storm, but a team from the JCAHO reportedly found that the deaths were caused by the critical nature of their illnesses rather than the severe flooding that inundated basements and other areas of the medical center. PMID- 11775429 TI - Hospitals report growing use of emergency phones for patients, staff. PMID- 11775430 TI - Clinical features of primary and metastatic hepatic malignancies. PMID- 11775431 TI - Chemoembolization and interstitial therapies for hepatocellular carcinoma. PMID- 11775432 TI - Diagnosis and management of intrahepatic and extrahepatic cholangiocarcinoma. PMID- 11775433 TI - Gallbladder cancer. AB - Gallbladder cancer often presents with advanced disease. When found early, surgery can be curative for this particular malignancy. Prognostic factors that influence the success of aggressive surgical therapy include depth of invasion, extent of hepatic infiltration, histologic grade, presence of venous, lymphatic or perineural invasion, and lymph node metastasis. Tumors with tumor limited to the subserosal layer, hepatic infiltration that is only 5 mm or less, papillary or well differentiated adenocarcinomas, tumors with no venous, lymphatic or perineural invasion and lymph node metastasis limited to the hepatoduodenal ligament have the best prognosis with surgery (15, 16, 36). Extended cholecystectomy with lymph node dissection has improved the results of treating T2 gallbladder cancers. More extensive resections should keep the above prognostic factors in mind. When surgical resection is not possible, endoscopic stenting of the biliary tree for palliation of obstructive jaundice is effective. Earlier detection or more effective chemotherapy will be needed to significantly improve the prognosis of this disease. PMID- 11775434 TI - Pathologic features of primary and metastatic hepatic malignancies. PMID- 11775435 TI - Malignant biliary obstruction: endoscopic approaches. PMID- 11775436 TI - Biology of liver metastases. AB - A primary goal of cancer research is an increased understanding of the molecular mechanisms mediating the process of cancer metastasis. Analyses of colon cancer cells (the seeds) and the microenvironment (the soil) have increased our understanding of the biologic mechanisms mediating metastasis formation. Insight into the molecular mechanisms regulating the pathobiology of colon cancer metastasis, as well as a better understanding of the interaction between the metastatic cell and the host environment (including the vasculature), should provide a foundation for new therapeutic approaches. To the clinician, it is readily apparent that by the time metastases form, most steps in the metastatic cascade have completed. Therefore, therapy to down-regulate or interrupt the last stages of metastasis, proliferation and angiogenesis as well as mechanisms to disrupt cell survival signals seems the most promising areas of investigation. PMID- 11775437 TI - Results of surgical resection for metastatic liver tumors. PMID- 11775438 TI - Resection for recurrent colorectal liver metastases. PMID- 11775439 TI - Surgical resection of hepatic tumors-patient selection and technical considerations. PMID- 11775440 TI - Radiofrequency ablation for primary and metastatic liver tumors. PMID- 11775441 TI - Cryosurgery for primary and metastatic liver tumors. PMID- 11775442 TI - Hepatic artery infusional chemotherapy for colorectal liver metastases. PMID- 11775443 TI - Pediatric liver tumors. PMID- 11775444 TI - Radiologic imaging and staging of primary and metastatic liver tumors. PMID- 11775445 TI - Results of surgical resection for hepatocellular carcinoma. AB - The overall prognosis of HCC is very poor because most patients are unresectable at the time of initial evaluation. Surgical resection is the only potentially curative treatment for HCC, however the recurrence rate after resection remains high as well. Utilizing screening protocols which incorporates the use of hepatic ultrasound and biochemical markers, HCC can be identified earlier and enable the patient to withstand surgical resection. Morbidity and mortality after resection is multifactorial and relates to HCC itself, underlying liver disease and comorbid conditions. Utilizing tests such as ICG R15, Redox Tolerance Index and Tc-GSA to define the functional status of the liver and staging systems helps define who will tolerate hepatic resection. Morbidity and mortality from hepatic resections has also improved with minimizing intraoperative blood loss and minimizing the amount of functional tissue resected. The use of maneuvers such as total vascular exclusion with or without venovenous bypass has expanded the indications for surgery. Utilizing therapeutic combinations, including TAE, portal vein embolization or ablative therapies widens the indications for resection of HCC. Since there are no chemotherapeutic regimens that have been found to prolong survival, surgical resection remains the procedure of choice for treating HCC. PMID- 11775446 TI - Indications and results of liver transplantation for primary and metastatic liver cancer. PMID- 11775447 TI - Ultrasound and ovarian cancer. AB - From the published studies it would appear that ultrasound is a very sensitive tool for identifying advanced stage ovarian cancer. The identification of Stage I ovarian cancer with ultrasound screening is more problematic since only 25 to 50% of ovarian cancers are identified in low-risk and high-risk respectively using this technique. Due to the low annual prevalence of ovarian cancer routine screening of premenopausal women or low-risk women after the menopause is unlikely to be cost-effective. The subject of biologic markers to screen for ovarian cancer is addressed elsewhere in this book. It is clear that a primary screening test less expensive than ultrasound is needed. The multicenter National Cancer Institute screening program is designed to evaluate possible new markers. At this time ovarian cancer screening should be done in high-risk groups under careful investigational scrutiny. Patients who are high-risk should be carefully advised of the limitations of diagnostic ultrasound in identifying early stage disease. Transvaginal ultrasound in expert hands is sensitive but not ideally specific for discriminating benign from malignant disease. The judicious use of color Doppler evaluation may help discriminate with greater specificity. PMID- 11775448 TI - Gene therapy. PMID- 11775449 TI - Normal ovarian surface epithelium. PMID- 11775450 TI - Cytopathology of the ovary. PMID- 11775451 TI - Telomerase and malignant transformation. PMID- 11775452 TI - Homeobox gene expression in ovarian cancer. PMID- 11775453 TI - EGF/ErbB receptor family in ovarian cancer. AB - In summary, the EGF/ErbB family of receptor tyrosine kinases has been shown to play a key role in normal ovarian follicle development, and cell growth regulation of the ovarian surface epithelium. Disregulation of these normal growth regulatory pathways, including overexpression and/or mutation of EGFR/ErbB receptor family members, as well as elements of their downstream signalling pathways, have been shown to contribute to the etiology and progression of epithelial ovarian cancer. It is, therefore, not surprising that these gene products, and their related soluble receptor isoforms may have clinical utility as tumor and/or serum biomarkers of disease activity. Moreover, since several of these soluble receptor isoforms have potent growth inhibitory activity, and are naturally occurring in the circulation, they are ideal candidates for the development of novel therapeutics for the treatment of ovarian cancer patients. PMID- 11775454 TI - Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer. AB - Lysophosphatidic acid (LPA), the simplest of all phospholipids, exhibits pleiomorphic functions in multiple cell lineages. The effects of LPA appear to be mediated by binding of LPA to specific members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors (GPCR). Edg 2, Edg4, and Edg7 are high affinity receptors for LPA, and Edg1 may be a low affinity receptor for LPA. PSP24 has been shown to be responsive to LPA in Xenopus oocytes, however, its role in mammalian cells is unclear. The specific biochemical events initiated by the different Edg receptors, as well as the biological outcomes of activation of the individual receptors, are only beginning to be determined. LPA levels are consistently elevated in the plasma and ascites of ovarian cancer patients, but not in most other epithelial tumors, with the exception of cervix and endometrium, suggesting that LPA may be of particular importance in the pathophysiology of ovarian cancer. In support of this concept, ovarian cancer cells constitutively and inducibly produce high levels of LPA and demonstrate markedly different responses to LPA than normal ovarian surface epithelium. Edg4 and Edg7 levels are consistently increased in malignant ovarian epithelial cells contributing to the aberrant response of ovarian cancer cells to LPA. Edg2 may represent a negative regulatory LPA receptor inducing apoptosis in ovarian cancer cells. Thus, increased levels of LPA, altered receptor expression and altered responses to LPA may contribute to the initiation, progression or outcome of ovarian cancer. Over 40% of known drugs target GPCR, making LPA receptors attractive targets for molecular therapeutics. Indeed, using the structure function relationship of LPA in model systems, we have identified selective Edg2 anatgonists, as well as Edg4 and Edg7 agonists. These lead compounds are being assessed in preclinical model systems. Understanding the mechanisms regulating LPA production, metabolism and function could lead to improved methods for early detection and to new targets for therapy in ovarian cancer. PMID- 11775455 TI - Expression of CSF-1 and its receptor CSF-1R in non-hematopoietic neoplasms. AB - CSF-1 and its receptor appear to be important in the physiology of several different neoplasms including those of the breast and female reproductive tract. Levels of CSF-1 and CSF-1R expression appear to correlate with tumor cell invasiveness and an adverse clinical prognosis and may be modulated by hormones involved in normal lactogenic differentiation. Also, it appears that CSF-1R activates several different signal transduction pathways but only some of these appear to have direct bearing on tumor cell phenotypes and the activation of pathways in specific cell types may depend on factors above and beyond the receptor itself. PMID- 11775456 TI - Risk assessment & genetic testing. AB - Ovarian cancer is the fifth most common cause of cancer death in women in Western countries and family history is one of the strongest known risk factors. Approximately 5 to 13% of all ovarian cancer cases are caused by the inheritance of cancer predisposing genes with an autosomal pattern of transmission. The inherited fraction of ovarian cancer may differ between populations. Based on analysis of familial ovarian cancer pedigrees and other epidemiological studies, three hereditary ovarian cancer syndromes have been defined. The identification of the genes responsible for most hereditary ovarian cancers has open a new area of early detection methods and preventive procedures specifically dedicated to women identified as carrying ovarian cancer predisposing genes. Predictive oncology is best performed by a dedicated unit with professionals aware of all the issues surrounding genetic testing. PMID- 11775457 TI - Role of inhibins and activins in ovarian cancer. PMID- 11775458 TI - The scientific basis of early detection of epithelial ovarian cancer: the National Ovarian Cancer Early Detection Program (NOCEDP). PMID- 11775459 TI - Adhesion molecules. AB - The exact mechanisms by which serous ovarian cancer cells invade through their underlying basement membrane or are released from the surface of the ovary have yet to be elucidated. This process undoubtedly has a complex molecular basis that most likely involves multiple cell surface receptors, basement membrane components, intercellular adhesion molecules, and signaling from the cell [137]. One possible mechanism by which ovarian carcinoma tumor cells may alter their basement membrane is by the synthesis and secretion of proteolytic enzymes that degrade their basement membranes [88-94, 138]. Alternatively, metastatic ovarian carcinoma cells may decrease their synthesis and/or secretion of ECM molecules. Additional studies are required to determine whether the more aggressive behavior of malignant ovarian carcinoma cells, compared to normal ovarian epithelial cells, is related to an altered cellular response towards ECM molecules, perhaps due to alterations in adhesion molecules/receptors. A further elucidation of the mechanisms by which serous ovarian carcinoma cells regulate their expression of ECM molecules and adhesion molecules/receptors will help in our understanding of the invasion and metastasis of tumor cells. Members of several families of adhesion molecules have been described that seem to be important in the progression of ovarian carcinoma, including CD44, integrins, and E-cadherin. Due to the complexity of this disease, it is likely that other adhesion molecules will also be implicated in the adhesion, migration, invasion, growth, proliferation, and apoptosis of ovarian carcinoma cells. Our group and others have shown that CD44 and the beta 1 integrin subunit play fundamental roles in the adhesion and migration of ovarian carcinoma cells to mesothelial cells and their associated pericellular matrix. Subsequent to the initial adhesion, the ovarian carcinoma cells may migrate through the layer of mesothelial cells, penetrate through the underlying basement membrane, invade into the tissue, and establish a secondary site of growth. Further studies will be required in order to fully understand the relationship of each adhesion molecule and their ligand(s) in the progression of this disease. Once the adhesion molecules and their ligand(s) for each step of the progression of this disease have been identified, it should be possible to develop reagents that can inhibit these interactions. Then, when ovarian carcinoma cells can no longer interact with mesothelial cells and their associated ECM, the dissemination of ovarian carcinoma cells in vivo may be prevented. PMID- 11775460 TI - Ovarian cancer-associated proteinases. PMID- 11775461 TI - Angiogenesis and metastasis. PMID- 11775462 TI - Early detection of ovarian cancer: promise and reality. PMID- 11775463 TI - Current diagnosis and treatment modalities for ovarian cancer. PMID- 11775464 TI - Incidence, mechanism, and natural history of scaphoid fractures. AB - Scaphoid fractures are fairly common and remain a difficult problem with respect to diagnosis, treatment, and outcome. The initial goal is accurate diagnosis of the fracture using clinical evaluation and available imaging modalities. Union is the subsequent objective, with a trend toward restoration of normal scaphoid anatomy, because nonunion or malunion may lead to unacceptable results and patient dissatisfaction. Despite biomechanical research of simulated fractures and clinical studies on natural history, the exact outcome after scaphoid union, nonunion, and malunion remains variable. PMID- 11775465 TI - The anatomy of the scaphoid. AB - The scaphoid is a critical link in the mechanism of the carpus. Its complex shape allows it to participate in the kinematics of both the proximal and distal row. Because of its offset proximal and distal articular surfaces, it has a natural tendency to palmar-flex with longitudinal loading. Because of this, extension of the scaphoid places progressively increasing tension on the palmar cortex of the curved waist of the scaphoid. Excessive extension or ulnar deviation of the wrist, coupled with excessive loading, mechanically predisposes the scaphoid to fracture. This is especially true if the strong ligaments attaching to the scaphoid retain their integrity. When a fracture occurs proximal to the waist of the scaphoid, it is predisposed to displacement because of the opposing forces on the proximal [table: see text] and distal fragments as well as the distribution of ligament attachments. This, in turn, predisposes the proximal fragment to ischemic conditions because of the distal location of nutrient vessels and a retrograde intraosseous blood supply. PMID- 11775466 TI - Effects of scaphoid fractures on the biomechanics of the wrist. AB - Scaphoid fractures are the most commonly fractured carpal bone. They most often occur from a fall on dorsiflexed, radially deviated wrist. The severity of the fall and position of the wrist influence the fracture pattern and the extent of ligamentous damage. Recent studies have correlated fracture pattern stability and any associated ligamentous disruption with the degree of alternation of wrist biomechanics. It is well documented that instability and altered kinematics can lead to nonunion and abnormal joint loads, which then can accelerate the onset of arthritis. Understanding these biomechanical consequences is critical when managing scaphoid fractures. PMID- 11775467 TI - Closed cast treatment of scaphoid fractures. AB - Cast immobilization of the wrist remains the treatment of choice for stable fractures of the waist and distal pole of the scaphoid. Criteria for diagnosis of stability should be stringent; plain radiographs may be misleading. CT may provide more accurate information on displacement. Immobilization of the thumb confers no advantage and restricts function unnecessarily. Evidence to support immobilization of the elbow is weak, but it may be useful for selected fractures. A cast does not protect the carpus from the effects of axial loading, which can produce large angulatory forces at the fracture. A gap or fracture offset of 1 mm or more are indicators of instability with potential for nonunion or malunion; internal fixation should be considered for these fractures. Internal fixation may also be considered routinely for proximal pole fractures, regardless of the degree of displacement, in view of their long healing time and high risk of nonunion after cast treatment. PMID- 11775468 TI - Percutaneous fixation of scaphoid fractures. AB - The scaphoid proximal pole and waist fractures presented here were treated by a novel dorsal percutaneous technique with arthroscopic assistance. All fractures healed, with good final functional results and no complications. The advantages of the dorsal percutaneous approach to scaphoid fixation are: (1) the proximal-to distal placement of the guide pin and screw allow for more precise placement along the central axis of the scaphoid, which decreases healing time and reduces risk of screw thread exposure. (2) The dorsal approach avoids injuring the vulnerable volar ligament anatomy. And (3) the insertion of the screw from the proximal to distal direction allows the more rigid fixation of proximal scaphoid fractures. Arthroscopy allows confirmation of fracture reduction and screw implantation as well as evaluation of concurrent ligament injuries not detected with standard imaging. Percutaneous K-wires act as joysticks to reduce and compress fracture fragments prior to fixation. The presented technique allows for early, rigid internal fixation with minimal associated morbidity. Patients successfully treated with this technique include those with stable and unstable acute fractures of the scaphoid at all locations, including the proximal pole. Nondisplaced fractures that present with delayed or fibrous union without evidence of avascular necrosis, cyst formation, or bony sclerosis may also be treated with this technique. This technique allows for faster rehabilitation and an earlier return to work or avocation without restriction once CT scan confirms a solid union. Some articles document extraordinary rapid healing by standard radiographs; however, we caution that scaphoid bone healing cannot accurately be determined without CT scan. Percutaneous, arthroscopically assisted internal fixation by a dorsal approach may be considered in all acute scaphoid fractures selected for surgical fixation. The dorsal guidewire permits dorsal and volar implantation of a cannulated screw along the central axis of the scaphoid. This technique permits the reduction of displaced fractures and the stable repair of fractures of the proximal pole. In addition, selected scaphoid fibrous union or delayed union may also be repaired, with realistic expectations of healing. The proven benefits of the percutaneous technique include decreased soft tissue trauma; arthroscopic visualization of the fracture, ensuring anatomic reduction; and stable fixation, allowing early physical rehabilitation. The theoretical benefits of the technique include decreased risk of interruption of the tenuous scaphoid blood supply. Percutaneous internal fixation of scaphoid fractures provides faster rehabilitation, earlier return to work, and quicker bony union in most patients. PMID- 11775470 TI - Open volar repair of acute scaphoid fractures. AB - Internal fixation of acute scaphoid fractures has significant advantages over conservative treatment, using cast immobilization. Healing rates are improved, functional recovery is accelerated, and morbidity is reduced. Percutaneous fixation has become the treatment of choice for the majority of acute fractures, since it is an out-patient procedure, which produces virtually no scarring and enables an extremely-rapid recovery; however, in those cases where a stable and anatomical reduction cannot be achieved by closed means, open volar repair remains the best method of treatment. With careful attention to technique, and the avoidance of postoperative immobilization, excellent results can be achieved, even in the case of transscaphoid fracture-dislocation of the carpus. PMID- 11775469 TI - Arthroscopic aided fixation of scaphoid fractures. AB - Acute nondisplaced scaphoid fractures have traditionally been managed with cast immobilization. Although cast immobilization may be successful in approximately 90% of cases, prolonged casting may lead to muscle atrophy, joint contracture, disuse osteopenia, and potential financial hardship. An athlete or worker may be inactive for 6 months or longer as the fracture heals. Arthroscopic assisted fixation offers a middle ground between traditional cast immobilization and open reduction for scaphoid fractures. These techniques reduce exposure and minimize soft tissue dissection with potential loss of vascularity, avoid division of the important radioscaphocapitate ligament, and allow for detection and management of any associated intracarpal soft tissue injuries. This article presents the indications and describes in detail the various applications for wrist arthroscopy in management of scaphoid fractures. PMID- 11775471 TI - Dorsal open repair of proximal pole scaphoid fractures. AB - Proximal pole fractures of the scaphoid are well suited for comprehension screw fixation. A dorsal approach allows for direct visualization of the fracture site, accurate reduction, and internal fixation. Bone grafting can also be achieved through the same incision without additional significant dissection. Successful uncomplicated union in the majority of cases with a considerably shortened period of immobilization has lead to a growing interest in this surgical procedure. PMID- 11775472 TI - Scaphoid nonunions. Pitfalls and pearls. AB - Our ability to treat scaphoid nonunions has improved dramatically. The degree of collapse and bone loss can be accurately assessed in waist fractures using sagittal images on CT scans. These nonunions require reduction and bone grafting to re-establish the normal geometry of the scaphoid. Magnetic resonance imaging helps evaluate whether or not avascular necrosis is present in the proximal pole. Because of the poor prognosis of conventional bone grafts, a vascularized bone graft is recommended as the primary treatment when AVN is present. The volar collapse of the humpback deformity is best corrected with a volar approach and the proximal pole nonunion is best approached using a dorsal approach. Nearly all proximal pole nonunions require a vascularized bone graft and all acute proximal pole fractures require open reduction and internal fixation. Using specially designed cannulated screws, the nonunions can be stabilized accurately to decrease the time to resolution of the nonunion and minimize the amount of time in a cast. Stable fixation requires that the screw fixation target the central portion of the scaphoid regardless of the type of screw design used. Using these techniques, the hand surgeon should be able to provide a reasonable prognosis for patients presenting with a scaphoid nonunion, and the treatment should result in functional range of motion, grip strength, and relief of pain. PMID- 11775473 TI - Scaphoid nonunion. Treatment with cancellous bone graft and Kirschner-wire fixation. AB - The wrist surgeon must be conversant with the many methods of treating scaphoid nonunions. Cancellous bone grafting combined with K-wire fixation is a relatively straightforward technique that has been shown in several studies to predictably produce healing of scaphoid nonunions. Although there may be a trend toward early use of vascularized bone grafts for the treatment of scaphoid nonunions, it would seem reasonable to reserve that procedure for cases in which the vascular supply to the scaphoid fragments is compromised, and for which there is little hope that a nonvascularized bone graft will succeed. PMID- 11775474 TI - Scaphoid nonunion and malunion. How to correct deformity. AB - This article reviews the historical evolution of the assessment and understanding of the deformity of the nonunited and malunited scaphoid. The preoperative assessment, planning, and surgical technique for restoration of scaphoid anatomy are described. A brief presentation of our midterm and long term results obtained with interpositional wedge grafting is also discussed. PMID- 11775475 TI - A vascularized bone graft for repair of scaphoid nonunion. AB - The majority of scaphoid fractures respond to casting, splinting, or open reduction and internal fixation. In patients who fail to heal a scaphoid fracture, several factors may contribute, including delay in treatment, fracture displacement, proximal third location, avascular necrosis, and associated carpal instability. PMID- 11775476 TI - Arthroscopic evaluation and treatment of scaphoid nonunion. AB - Scaphoid fractures are one of the most common carpal fractures and heal without complication in a majority of cases. Nonunion of the scaphoid, unfortunately, can occur secondarily to several reasons; namely, delay in treatment, delay in diagnosis, the intra-articular nature of the fracture, the precarious vascular supply of the scaphoid, and significant biomechanical stresses across the fractured scaphoid. PMID- 11775477 TI - Proximal row carpectomy for the treatment of scaphoid nonunion. AB - Nonunion of the scaphoid bone may occur even with early diagnosis of fracture and modern internal fixation techniques. A pattern of degenerative instability termed scaphoid nonunion advanced collapse may lead to collapse of the carpus with irreversible articular damage initially isolated to the radiostyloid joint. Proximal row carpectomy (PRC), which removes the intercalary proximal row and creates a radiocapitate articulation, is a motion preserving salvage procedure which unloads the areas of articular pathology, and creates a new articulation that allows motion and is able to bear compressive forces over time. Although results of PRC specifically for scaphoid nonunion are clearly not reported in the article, several studies demonstrate that PRC provides a pain relieving and motion-sparing salvage option particularly suited for this condition. PMID- 11775478 TI - Intercarpal fusion for the treatment of scaphoid nonunion. AB - Salvage of the ununited scaphoid may not always be feasible or advisable, hence the availability of a number of alternative techniques which prioritize restoration of pain relief and range of motion. The role of intercarpal fusion reflects the importance of midcarpal stabilization when the scaphoid is resected. While scaphocapitate and scaphocapitolunate fusions have been described, these techniques provide less pain relief than midcarpal fusion with scaphoid excision, and are associated with an increased risk of radioscaphoid arthritis. In this article, the author will address the rationale for, technique of, and outcome after midcarpal arthrodesis and scaphoid excision. PMID- 11775479 TI - Partial excision of scaphoid: is it ever indicated? AB - The carpal scaphoid cannot be partially or totally excised without paying a functional penalty, usually in the form of carpal instability. In selected conditions, however, a partial scaphoidectomy may be preferred over other less reliable alternatives. These include excision of a small fragment of a fractured proximal pole when there is no injury to the scapholunate ligaments; excision of the distal fragment of a nonunited, arthritic distal-third scaphoid fracture; resection-arthroplasty of isolated STT osteoarthritis; and distal scaphoid excision to improve midcarpal function after a radioscapholunate fusion. In this article, both the pathomechanics and clinical results of such techniques are discussed. PMID- 11775481 TI - Methods of imaging the scaphoid. AB - Rapid diagnosis of a scaphoid fracture is important so that proper treatment may be initiated. The high frequencies of nonunion of proximal pole, AVN, and scaphoid fractures warrant the use of special imaging to identify an occult fracture that may cause a long-term disability if not diagnosed. The modalities discussed allow the reader to treat patients in an expeditious and accurate manner. PMID- 11775480 TI - Electrical and ultrasound stimulation for scaphoid fractures. AB - The standard treatment for delayed union or nonunion of the scaphoid is operative management. Electrical stimulation has been employed in these clinical situations in patients unable or unwilling to undergo surgical intervention. Recent interest has also focused on the use of low-intensity ultrasound as an adjunct to healing in distal radius and tibial fractures. Results with the use of ultrasound for scaphoid fractures is encouraging. A review of the mechanisms of action, clinical results, and possible indications is presented for these two nonoperative modalities. PMID- 11775482 TI - One hundred ... and counting! PMID- 11775483 TI - The power of presence. PMID- 11775484 TI - Caring for Jose. PMID- 11775485 TI - Timmy pats. PMID- 11775486 TI - In praise of master teachers: a little less deaf, a little less dumb. PMID- 11775487 TI - Up the slope: physician-assisted suicide and the infamous slippery slope. PMID- 11775488 TI - Treatment of lice. PMID- 11775489 TI - Upper gastroenteral bleeding from artery of Dieulafoy: 2 cases. PMID- 11775490 TI - A modified technique to treat subdural hematomas: the subdural evacuating port system. AB - BACKGROUND: The Subdural Evacuating Port System (SEPS) is intended for drainage of subdural fluid collections such as hygromas and hematomas. Unlike other subdural fluid drainage systems, no drain is placed in the subdural space. This paper describes the technique and reports our experience thus far. METHODS: We treated 20 patients for 22 subdural hematomas. One or two ports were inserted for drainage of each subdural collection. Follow-up ranged from six to 24 months. RESULTS: Follow-up CT obtained at approximately one month postprocedure showed complete or near complete resolution of 18 of the subdural collections. Failure of the SEPS was noted in four patients and was related to plugging of the drainage system by clots secondary to the presence of fresh blood in the subdural collection. CONCLUSIONS: The Subdural Evacuating Port System (SEPS) permits the neurosurgeon to drain subacute or chronic hematomas by a method which is minimally invasive, simple and safe. PMID- 11775491 TI - Genetic aspects of chronic pancreatitis: insights into aetiopathogenesis and clinical implications. AB - The recent genetic discoveries in CP support the hypothesis that inappropriate intrapancreatic activation of zymogens by trypsin results in autodigestion and pancreatitis. Two different protective mechanisms prevent activation of the pancreatic digestive enzyme cascade. First, SPINK1 inhibits up to 20% of potential trypsin activity and, second, trypsin itself activates trypsin-like enzymes readily degrading trypsinogen and other zymogens. Pancreatitis may therefore be the result of an imbalance between proteases and their inhibitors within the pancreatic parenchyma. The discovery of PRSS1 mutations in families with CP was the first breakthrough in the understanding of the underlying genetic mechanisms. Enhanced trypsinogen activation may be the common initiating step in pancreatitis caused by these mutations. The discovery of SPINK1 mutations underlines the importance of the protease inhibitor system in the pathogenesis of CP. Thus, gain-of-function in the cationic trypsinogen resulting in an enhanced autoactivation, or loss-of-function mutations in SPINK1 leading to decreased inhibitory capacity, may similarly disturb the delicate intrapancreatic balance of proteases and their inhibitors. The recent findings of SPINK1, CFTR, and PRSS1 mutations in CP patients without a family history have challenged the concept of idiopathic CP as a non-genetic disorder and the differentiation between HP and ICP. There is a clear mode of autosomal dominant inheritance for some mutations (R122H, N291, possibly MIT), whereas the inheritance pattern (autosomal recessive, complex, or modifying) of other mutations (A16V, N34S) is controverted or unknown. The lack of mutations in the above-mentioned genes in many patients suggests that CP may also be caused by genetic alterations in yet unidentified genes. Evaluation of CP patients without an obvious predisposing factor, e.g. alcohol abuse, should include genetic testing even in the absence of a family history of pancreatitis. Finally, identification of further disease-causing genes will create a better understanding of pathogenesis and may help to develop specific preventive and therapeutic strategies. PMID- 11775492 TI - Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children's Hospital Basel. AB - OBJECTIVE: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. METHODS: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000. RESULTS: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients. Overall, bacteria were isolated from 53 patients (65%) with Staph. aureus as the most frequent organism (n = 31; 50%). BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates. In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests. Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI. 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates. Median duration of hospitalisation was 15 days (range 2-66). CONCLUSION: Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC. Of supportive laboratory parameters, ESR and CRP were most valuable in our hands. PMID- 11775493 TI - Intramedullary spinal cord tumours: a clinical outcome and radiological follow-up study. AB - PRINCIPLES: Intramedullary spinal cord tumours are rare. The long-term results depend on their varying natural histories and the surgical approach. Less extensive tumour resection avoids greater postoperative neurological impairment without a negative impact on postoperative outcome. METHODS: Twenty-seven patients who underwent a total of 34 surgical interventions (including 7 reoperations) were clinically and radiologically reinvestigated. Histology revealed 19 glial, 4 nonglial and 4 miscellaneous tumours. RESULTS: Postoperative long-term clinical follow-up (mean 62 months postoperatively) in 25 patients revealed functional improvement in 2 cases, stable conditions in 17 and deterioration in 6. Although there was residual tumour on MRI in 19 of the 22 patients reexamined, stable radiological studies were seen in 15 cases. Despite the high percentage of partial resections or biopsies, good long-term clinical results were found in 19 patients (70%). CONCLUSION: The long-term outcome depends on tumour biology and the type of surgery. For low-grade astrocytomas we propose partial resection without incurring the risk of major postoperative neurological deficits, with semi-annual and, after 5 years, annual follow-up. Despite the fact that ependymomas are amenable to complete surgical resection, this was achieved in only one of six cases in this series. Postoperative MRI follow-up of intramedullary tumours must be protracted, as most of these tumours are slow-growing. An increase in the extent and intensity of contrast enhancement of the tumours was defined as tumour recurrence or progressive tumour growth. PMID- 11775494 TI - A profile of journals of complementary and alternative medicine. AB - An increasing amount of medical scientific information is published in specialised journals on various subjects, including complementary and alternative medicine (CAM). There are indications that positive findings may be published at the expense of methodological rigour. The aim of this investigation was to provide a profile of CAM journals currently available on Medline, and monitor trends in publication practice between the years 1995 and 2000. Systematic literature searches were performed to identify all CAM journals indexed in Medline. Journals published in 1995 and 2000 were identified by their title and content. Primary CAM research journals only were included in this analysis. All articles were read, data were extracted and categorised according to pre-defined criteria, e.g. type of methodology used, subject area, and direction of outcome. The number of original articles increased from a total of 61 in 1995 to 97 in 2000 across all four journals, the number of papers reporting clinical trials decreased by 4% between 1995 and 2000, and the number of surveys increased more than six times. Less positive and more negative articles were published in 2000 compared with 1995. The subject areas of papers varied greatly. The majority of articles published in 1995 suggested positive treatment effects, a phenomenon that was still present in 2000 albeit less strong. CAM journals, and most likely CAM itself, are associated with a lack of clinical trials and a bias in favour of positive conclusions. PMID- 11775495 TI - Cork and smoke. PMID- 11775496 TI - Evaluating the accuracy of the benefit transfer method: a rural water supply application in the USA. AB - Due to declining federal, state, and local government budgets, there is an increasing need to analyze the benefits of government funded programs to determine where increasingly limited funds would best be spent. The benefits transfer technique is analyzed for the development of a rural water supply system and guidelines for successful benefits transfer are presented. Benefit transfer appears to provide reasonably accurate estimates of natural resource benefits if a broad based benefit model is used. The benefits-transfer-based estimates are accurate as long as a model based on data from a wide variety of conditions is used or the model is based on data from a very similar region. The wide-based data modeling approach has the greatest practical application. These findings are based upon contingent valuation data obtained from four sites in the western USA. PMID- 11775497 TI - A comparison of sustainability theory with UK and European airports policy and practice. AB - There are three main theoretical difficulties involved in relating sustainability to aviation, and which a research agenda for sustainable aviation needs to address. The first is uncertainty regarding the critical thresholds of global environmental systems. The second is a lack of protocols for allocating permissible environmental consumption shares to, and hence targets for, individual enterprises or sectors. The third is differing value judgements of what natural features should be sustained. For the time being, these difficulties preclude determination of the degree of sustainability or unsustainability of any individual airport with respect to global environmental systems. Nevertheless, at this stage it can at least be said that since most economic activity has an adverse environmental impact, airports with higher throughputs of material and people will tend to be less sustainable than smaller-scale airports given similar technologies and regulatory compliance. This is theoretically supported and illustrated with waste arising as an indicator at reviewed airports. Despite governmental policies of sustainable mobility, there is a disjunction between EU and UK policy on airports and individual airport practice, and environmental sustainability theory. In the UK and EU, airport practice and governmental policy is to mitigate the impacts of aviation, but not at the expense of its aviation growth. This mitigation practice is summarised for the reviewed airports and presented in a framework that accounts for the suggested, interim approach to sustainability assessment. PMID- 11775498 TI - Risk-based targeting of diffuse contaminant sources at variable spatial scales in a New Zealand high country catchment. AB - Management of agricultural diffuse pollution requires targeting or prioritising critical source areas at various spatial scales within watersheds. This study develops, evaluates and illustrates a risk-based approach for assessment and targeting of source areas at catchment, subarea and individual farm scales. Catchment water quality data are used in conjunction with information on watershed characteristics from the New Zealand Land Resources Inventory at the subarea scale and land use information at the farm scale to assess risk and target source areas. Total phosphorus in the Lake Hayes Catchment, a high country pastoral catchment in the South Island of New Zealand, is used as a case study. Use, comparison and evaluation of several different methodologies for subareas and individual properties showed that a subarea in the upper catchment and one immediately upstream from the lake were the worst source areas. Targeting of other subareas varied dependent on the method used. The worst individual properties were targeted based on the combination of intensity of cattle and sheep grazing, fertilizer usage, bank erosion and location in the worst subareas. Water quality results are critical to successful targeting, particularly for convincing landowners that streams will benefit from best management practices on their properties. In addition to concentrations, average and extreme loadings are important. Data on catchment characteristics, particularly land use, are needed for targeting, but are not always readily available at small scales. This study demonstrated simple but useful methods for application of assessment information for quantitative targeting of contaminant source areas at different spatial scales. PMID- 11775499 TI - Towards participatory environmental management? AB - While the mainstream approach to environmental management (EM) has tended to be centralized, adopting a narrow conception of 'environment', there is a growing body of literature supporting a participatory approach which is decentralized, community oriented and holistic in its view of the environment. This paper examines the main principles underlying this development and assesses the opportunities and constraints associated with it. It concludes that, while participation is conducive to a localized and inclusive approach to EM, many questions remain about the extent to which it is meaningful in practice or can be institutionalized. PMID- 11775500 TI - Using a GIS model to assess terrestrial salamander response to alternative forest management plans. AB - A GIS model predicting the spatial distribution of terrestrial salamander abundance based on topography and forest age was developed using parameters derived from the literature. The model was tested by sampling salamander abundance across the full range of site conditions used in the model. A regression of the predictions of our GIS model against these sample data showed that the model has a modest but significant ability to predict both salamander abundance and mass per unit area. The model was used to assess the impacts of alternative management plans for the Hoosier National Forest (Indiana, USA) on salamanders. These plans differed in the spatial delineation of management areas where timber harvest was permitted, and the intensity of timber harvest within those management areas. The spatial pattern of forest openings produced by alternative forest management scenarios based on these plans was projected over 150 years using a timber-harvest simulator (HARVEST). We generated a predictive map of salamander abundance for each scenario over time, and summarized each map by calculating mean salamander abundance and the mean colonization distance (average distance from map cells with low predicted abundance to those with relatively high abundance). Projected salamander abundance was affected more by harvest rate (area harvested each decade) than by the management area boundaries. The alternatives had a varying effect on the mean distance salamanders would have to travel to colonize regenerating stands. Our GIS modeling approach is an example of a spatial analytical tool that could help resource management planners to evaluate the potential ecological impact of management alternatives. PMID- 11775501 TI - Identification of river water quality using the fuzzy synthetic evaluation approach. AB - Proper identification of water quality conditions in a river system based on limited observations is an essential task for meeting the goals of environmental management. Various classification methods have been used for estimating the changing status and usability of surface water in river basins. However, a discrepancy frequently arises from the lack of a clear distinction between each water utilisation mode, the uncertainty in the quality criteria employed and the vagueness or fuzziness embedded in the decision-making output values. Owing to inherent imprecision, difficulties always exist in some conventional methodologies when describing integrated water quality conditions with respect to various chemical constituents, biological aspects, nutrients, and aesthetic qualities. This paper presents a comparative study using three fuzzy synthetic evaluation techniques to assess water quality conditions in comparison to the outputs generated by conventional procedures such as the Water Quality Index (WQI). Based on a set of data collected at seven sampling stations, a case study for the Tseng-Wen River system in Taiwan was used to demonstrate their application potential. The findings clearly indicate that the techniques may successfully harmonise inherent discrepancies and interpret complex conditions. A further, newly developed fuzzy synthetic evaluation approach described in this paper might also be useful for verifying water quality conditions for the Total Maximum Daily Load (TMDL) program and be helpful for constructing an effective water quality management strategy. PMID- 11775502 TI - Climate extremes and adaptive management on the Colorado River: lessons from the 1997-1998 ENSO event. AB - The Colorado River system exhibits the characteristics of a heavily over allocated or 'closing water system'. In such systems, development of mechanisms to allow resource users to acknowledge interdependence and to engage in negotiations and agreements becomes necessary. Recently, after a decade of deliberations and environmental assessments, the Glen Canyon Dam Adaptive Management Program (GCDAMP) was established to monitor and analyze the effects of dam operations on the Grand Canyon ecosystem and recommend adjustments intended to preserve and enhance downstream physical, cultural and environmental values. The Glen Canyon Dam effectively separates the Colorado into its lower and upper basins. Dam operations and adaptive management decisions are strongly influenced by variations in regional climate. This paper focuses on the management of extreme climatic events within the Glen and Grand Canyon Region of the Colorado River. It illustrates how past events (both societal and physical) condition management flexibility and receptivity to new information. The types of climatic information and their appropriate entry points in the annual cycle of information gathering and decision-making (the 'hydro-climatic decision calendar') for dam operations and the adaptive management program are identified. The study then describes how the recently implemented program, lessons from past events, and new climate information on the Colorado River Basin, facilitated responses during the major El Nino-Southern Oscillation (ENSO) event of 1997-1998. Recommendations are made for engaging researchers and practitioners in the effective use of climatic information in similar settings where the decision stakes are complex and the system uncertainty is large. PMID- 11775503 TI - A framework for assessing the impact of the IPPC directive on the performance of the pig industry. AB - New European Union legislation on Integrated Pollution Prevention and Control (IPPC) is being implemented in the United Kingdom, enacted by the Pollution Prevention and Control Act 1999 and its statutory instruments, the Pollution Prevention and Control (England and Wales) Regulations 2000. This legislation incorporates previously unregulated installations in the food and intensive livestock sectors, such as pig installations above a given threshold size. IPPC requires that installations adopt Best Available Techniques and follow General Binding Rules of good practice in order to manage their environmental effects. IPPC has significant potential impacts for both the environmental and financial performance of the pig industry. In this context, the paper discusses the IPPC implementation process as it applies to the sector and presents a methodological framework for assessing the environmental and cost benefit implications of the new regulations. PMID- 11775504 TI - September 11, 2001: a pictorial report. PMID- 11775505 TI - Biological weapons of mass destruction. PMID- 11775506 TI - Tight economy swells demand for case management certification. PMID- 11775507 TI - Office CM program draws praise from physicians. PMID- 11775508 TI - LOS misleading indicator for hip fracture, some say. PMID- 11775509 TI - Cover your bases with EMTALA algorithm. PMID- 11775510 TI - The enigma of tinnitus. PMID- 11775511 TI - Patchy tympanosclerosis (cosmetic). PMID- 11775512 TI - Vocal fold varicosity manifesting as a recurrent hemorrhage. PMID- 11775513 TI - Nasal malignancy masquerading as polyposis: importance of biopsy in powered endoscopic sinus surgery. PMID- 11775514 TI - Perineural tumor spread from a palatal carcinoma. PMID- 11775515 TI - Unilateral tinnitus occurring with a peripheral vestibular disorder in the contralateral ear. PMID- 11775516 TI - Replacement of a failed tracheoesophageal puncture prosthesis under direct vision. PMID- 11775517 TI - Central tinnitus: a case report. AB - We report a case of acute-onset unilateral tinnitus in a 25-year-old woman. Analysis of imaging studies indicated that the tinnitus was likely caused by an acute hemorrhage of a small cavernous angioma that was located adjacent to the contralateral primary auditory cortex. This case provides substantial support for the concept that central tinnitus might indeed represent a pathologic activation of neural networks of nonspecific auditory perception. PMID- 11775518 TI - Panic disorder in otolaryngologic practice: a brief review. AB - Panic disorder is typically characterized by a sudden, inexplicable feeling of terror and a fear that one is losing control, "going crazy," or on the verge of death. Because these anxiety attacks can appear spontaneously and unpredictably, they often create a companion state in which the patient continually worries about when the next attack will occur. Left untreated, panic disorder can be seriously debilitating and can progress to the development of phobias and impose severe limitations on quality of life. Otolaryngologists are likely to see patients with panic disorder, particularly those who have complaints of dizziness, tinnitus, or extraesophageal manifestations of gastroesophageal reflux. This article briefly reviews the diagnosis and treatment of panic disorder. PMID- 11775519 TI - Sigmoid sinus thrombosis with contralateral abducens palsy: first report of a case. AB - Intracranial complications of acute and chronic otitis media can be difficult to recognize because the signs and symptoms are often subtle. This article describes a case of one such complication--sigmoid sinus thrombosis--that was manifested by a contralateral abducens palsy. The author believes that this is the first reported case of such an occurrence. This article also reviews the differential diagnosis of increased intracranial pressure and discusses the recognition and management of lateral sinus thrombosis. PMID- 11775520 TI - Myxoid angiomyoma of the hard palate: a case report. AB - Angiomyomas are found with some frequency in the female genital tract. They can also appear in both sexes in the gastrointestinal tract and in the skin. The oral cavity is an unusual site for an angiomyoma. In this article, we describe the case of a 74-year-old woman who came to us with a nodule at the palatal midline. Following surgical excision of the growth and stent placement over the wound site, a biopsy analysis was performed. Histology of the removed tissue revealed an unusual variant of an angiomyoma: a myxoid angiomyoma. PMID- 11775521 TI - A case of laryngeal carcinoma appearing as a goiter. AB - We describe the case of a 41-year-old man with hoarseness and a hard, fixed mass in the anterior cervical region. He was referred to our endocrinology service for evaluation of possible thyroid cancer. The results of laboratory tests of thyroid function were normal. Indirect laryngoscopy revealed paralysis of the left hemilarynx and the presence of a large vegetating lesion. Computed tomography of the neck disclosed the presence of a mass in the anterior region, along with invasion and destruction of the adjacent structures. The cytologic diagnosis was established by analysis of a fine-needle aspiration biopsy specimen, which revealed a squamous cell carcinoma. The final diagnosis was carcinoma of the larynx. PMID- 11775522 TI - Spontaneous vertigo and headache: endolymphatic hydrops or migraine? AB - We undertook a study to assess whether patients who had both spontaneous vertigo and headache would respond to treatment for endolymphatic hydrops rather than treatment for migraine. We also attempted to discover if there were any individual characteristics that might predict which patients with an equivocal history and symptoms would be more likely to have either of the two conditions as opposed to the other. All patients were initially treated for endolymphatic hydrops with sodium restriction and increased water intake. Response to treatment was assessed by three tools: the Dizziness Handicap Inventory, a symptom severity scale, and a disability scale. Patients who did not respond to treatment for endolymphatic hydrops were switched to treatment for migraine. At the first follow-up period, 23 patients were available for analysis by telephone survey. According to data obtained by the three assessment tools, 14 patients (60.9%) improved after initial therapy and six (26.1%) improved following subsequent migraine treatment; the remaining three patients (13.0%) did not comply with their initial treatment regimen, and they showed no improvement. Although no statistically significant conclusions can be drawn because of the small sample size, there were trends to suggest that certain demographic, clinical, and objective-testing characteristics might predict which patients are likely to have one of these two conditions as opposed to the other. We conclude that a stepwise approach to treatment, beginning with therapy for endolymphatic hydrops, is an appropriate strategy. Also, the fact that no improvement was seen among the three patients who did not comply suggests that improvement is indeed the result of treatment rather than simply a function of the passage of time. PMID- 11775523 TI - Sphenoid sinus mucocele: a rare complication of transsphenoidal hypophysectomy. AB - Only seven cases of a sphenoid mucocele occurring after transsphenoidal hypophysectomy have been previously reported in the world literature. In this article, we report a new case, which occurred in a 67-year-old man. The sphenoid sinus mucocele developed 12 years following transsphenoidal hypophysectomy and adjunctive radiotherapy. The patient was successfully managed with incision and drainage. Although transsphenoidal hypophysectomy is a common operation, this particular complication appears to be rare or at least under-reported. Sphenoid sinus mucocele deserves consideration in the differential diagnosis of a sphenoidal parasellar mass in a patient who has undergone an earlier transsphenoidal hypophysectomy. PMID- 11775524 TI - Microscopic removal of an embedded foreign body from the hypopharynx: report of two cases. AB - Incidents of foreign bodies in the hypopharynx, especially fish bones, are very common. In most cases, these bones can be easily located and removed. However, in other cases, they become embedded in the pharyngeal wall and cannot be located, even by fiberoptic endoscopy and rigid esophagoscopy. Left in place, these foreign bodies can eventually cause serious complications. We treated two patients who had an embedded foreign body in the hypopharyngeal wall that we were unable to locate by fiberoptic endoscopy and rigid esophagoscopy. Ultimately, we performed direct laryngoscopy and were able to locate and remove the foreign bodies with the aid of a microscope. PMID- 11775525 TI - Is imaging necessary in the evaluation of the patient with an isolated complaint of anosmia? AB - Imaging studies are often obtained during the evaluation of the patient with an olfactory deficit. The purpose of this article is to describe an investigation that was conducted to assess the effectiveness of imaging studies in determining the etiology of olfactory loss in the patient with an isolated complaint of anosmia and no relevant findings on physical examination, including nasal endoscopy. The author conducted a retrospective review of the records of 20 women and eight men, aged 22 to 71 years (mean: 45), whose duration of anosmia had ranged from 1 month to 2 years (median: 3 mo). Twenty of these patients had undergone contrast-enhanced magnetic resonance imaging of the paranasal sinuses and brain, and the other eight had undergone enhanced computed tomography. The author found that these imaging studies did not add to the information obtained by the clinical history and endoscopic nasal examination and were thus not useful in determining the cause of anosmia. Based on these findings, the author does not recommend that imaging studies be included as part of the evaluation of these patients. PMID- 11775526 TI - Options for preserving the larynx in patients with advanced laryngeal and hypopharyngeal cancer. AB - The introduction of newer surgical and combined-modality approaches to organ preservation in patients with advanced laryngeal or hypopharyngeal cancer is the most exciting clinical frontier in head and neck cancer treatment today. The use of these techniques at other sites, the exploration of improved methods for patient selection and tumor assessment, and the development of newer combination regimens will need to be rigorously studied in future clinical trials. In all these efforts, the major focus must remain on improving survival. This article reviews the latest developments in organ-preservation strategies and techniques for patients with advanced laryngeal or hypopharyngeal cancer. PMID- 11775527 TI - Interference of government with individual medical practices. PMID- 11775528 TI - Endoscopic physiologic approach to allergy-associated chronic rhinosinusitis. PMID- 11775529 TI - Establishment of labeling primer reverse transcription in situ polymerase chain reaction and detection of hepatitis C virus in liver tissues. AB - OBJECTIVE: To establish bio-11-photosoralen (BP) labeling primer reverse transcription in situ polymerase chain reaction (PCR), and to detect the location and distribution of hepatitis C virus in 30 cases liver tissues embedded with paraffin. METHODS: BPs were labeled in tymidine (T) position under ultraviolet lamp. The method was compared with indirect RT-in situ PCR and in situ hybridization for detecting hepatitis C virus (HCV) RNA. RESULTS: Serum HCV PCR and southern blot showed that BP labeling psimer PCR was possible, and had a good specificity. The HCV positive rate was 53% (16/30) by indirect in situ PCR, 50% (15/30) positive specimens were found by BP labeling primer in situ PCR. Statistical analysis revealed P > or = 0.05 and the two methods had no dominant differences. Meanwhile, only 23% (7/30) positive signals were seen by in situ hybridization, which was lower than two in situ PCR(P < or = 0.05). HCV was mainly located in hepatic-plasmas, and positive signals were found in monocytes and cholangiolar epithelia. CONCLUSIONS: Both indirect in situ PCR and BP labeling in situ PCR have good sensitivity and specificity for detecting HCV RNA of liver tissues. HCV RNA is located in hepatocytes, monocytes and cholangiolar epithelia. PMID- 11775530 TI - Long-term survey of outcome in acute promyelocytic leukemia. AB - OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL. PMID- 11775531 TI - Mitochondrial gene variation in type 2 diabetes mellitus: detection of a novel mutation associated with maternally inherited diabetes in a Chinese family. AB - OBJECTIVE: To explore the relationship between type 2 diabetes mellitus and the mutation(s) in mitochondrial DNA. METHODS: According to the previous literature, the fragment of mitochondrial DNA from nucleotide 3153 to 3551, which had shown high frequency of point mutation, was scanned with the technique of polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) in Chinese normal control, type 2 diabetic population, and 12 families suffered from maternally inherited type 2 diabetes mellitus. Direct sequencing was applied to detect the fragments with abnormal conformation. RESULTS: No special band was found in SSCP electrophoreses in Chinese normal control, and only one subject (No. 81) of diabetic population indicated the abnormality in SSCP study, which was affirmed to be a silent point mutation of T to C at nucleotide 3336 inducing no change in amino acid (ATT-->ATC, Ile). Pedigree 25,001 was the only family that exhibited strongly different SSCP characteristic from the other 11 ones, which was confirmed to be caused by a single point mutation mt3285T-->C/T in the coding region of tRNA(Leu(UUR)) gene by the technique of direct sequencing. CONCLUSIONS: The variation within mt DNA 3153-3551 is not the major cause of type 2 diabetes in Chinese population suffered from this disease in this study. The point mutation T-->C/T at the mitochondrial nucleotide 3285, which was found in pedigree 25,001, is located in the highly conservative region of tRNA(Leu(UUR)) gene. It is strongly suggested that this mutation cause the conversion in the 3 dimentional structure of tRNA(Leu(UUR)), which might disturb the normal translation and lead to the impairment in mitochondrial oxidative phosphorylation characterized by the defects of the polypeptides involved in the respiratory chain. Thus, insulin secretion deficiency and insulin resistance might occur. PMID- 11775532 TI - High frequency loss of heterozygosity in the region of the DBH locus in bladder cancer. AB - OBJECTIVE: To determine the location of a putative tumor suppressor gene (TSG), and evaluate the frequency loss of heterozygosity (LOH) of the long arm of chromosome 9 (9q) in bladder cancer. METHODS: We analyzed 25 patients with bladder cancer for LOH of 9q using 25 high-density microsatellite markers. RESULTS: Twenty-three samples (92%) showed LOH at least at one locus on 9q. We identified that the commonly deleted region were at 9q12-q21, 9q22, and 9q34. The rate of LOH was 44.0%, 22.7%, 22.7%, 16.0%, 12.0% on DBH, D9S15, D9S1815, D9S1831, D9S176 locus, respectively, and was not significantly related with grades and stages of tumor. CONCLUSION: These data suggest that alteration of a TSG at DBH of 9q may play an important role in the development of bladder cancer. PMID- 11775533 TI - Impaired gp-91phox gene expression and dysfunction of peripheral blood neutrophils in patients maintaining hemodialysis. AB - OBJECTIVE: To investigate expressions of gp-91phox and IL-8 gene and the function of neutrophils in hemodialysis (HD) patients, and to understand the relationship between uremia and immune. METHODS: Gene expression was studied by means of reversal transcription polymerase chain reaction (RT/PCR) from the untreated and treated with lipopolysaccharide (LPS) neutrophils in controls and HD patients. Phagocytosis and bactericidal assays were measured as a decrease in the number of viable intracellular and extracellular bacteria by colony counts. RESULTS: Freshly isolated neutrophils express gp-91phox mRNA in controls while no gp 91phox mRNA was detected in HD patients. When challenged with LPS, gp-91phox mRNA exhibited decreased expression. IL-8 mRNA in HD patients could be spontaneously expressed. Phagocytosis and intracellular killing of neutrophils, when exposed to Staphylococcus aureus, were decreased obviously compared with controls. CONCLUSIONS: The impaired gp-91phox gene expression of neutrophils indicates the impaired NADPH-oxidase system and the untreated neutrophils spontaneously express IL-8 mRNA in the HD patients, which is consistent with suppressed phagocytosis and intracellular killing capacity. PMID- 11775534 TI - Effect of 1,25(OH)2D3 on the growth and apoptosis of breast cancer cell line MCF 7. AB - OBJECTIVE: To study the effect of 1, 25-dihydroxyvitamin D3(1,25(OH)2D3) on the growth and apoptosis of breast cancer cell line MCF-7. METHODS: Cell number was determined using the MTT method. Flow cytometric analysis was performed on cell cycles, and the percentage of apoptosis was counted. Apoptotic cells were quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and bcl-2 protein expression was estimated with Western blotting. RESULTS: After incubation with 1,25(OH)2D3 10(-7) mol/L for 48 hours, MCF-7 cells exhibited significant growth in a dose- and time-dependent manner. Flow cytometric analysis indicated that cell numbers in G0/G1 increased along with increasing apoptotic peak and percentage. With microscope and electron microscope observation, characteristics of apoptosis such as typical apoptotic bodies were commonly found. TUNEL also showed that 1,25(OH)2D3 10(-8) mol/L and 10(-7) mol/L groups had significantly high apoptosis percentage than control group with dose-dependence on induction apoptosis. And Western blot showed that 1,25(OH)2D3 10(-8) mol/L could down-regulate bcl-2 protein and 10(-7) mol/L could almost block bcl-2 protein expression. CONCLUSIONS: 1,25(OH)2D3 can inhibit cell growth with G0/G1 arrest, enhance the proliferation inhibition action of adriamycin, and induce apoptosis which may result from the down-regulation of the anti-apoptotic bcl-2 protein. PMID- 11775535 TI - Diagnosis and surgical treatment of posterior fossa solid hemangioblastomas. AB - OBJECTIVE: To elucidate the diagnosis and surgical treatment of the posterior fossa solid hemangioblastomas (PFSHs). METHODS: The data from 22 patients with PFSHs verified by surgery and pathology were analyzed retrospectively and a review of relevant literature was conducted. RESULTS: The preoperative definitive diagnosis rate was 13/22. Total tumor removal was achieved in 20 patients. Two of the 22 patients died after surgery, one of brain-stem injury and the other from an intracranial hemorrhage. Twenty patients were followed up for 2 months to 8 years (average, 2 years). Kamofsky scale was > or = 80 in 15 patients, 60-70 in 1 patient and not measured in 4 patients who died during follow-up. The causes of death were pneumonia (2 patients) and purulent meningitis (2). CONCLUSION: MRI and DSA (digital subtraction angiography) are major preoperative diagnostic modalities for PFSH, but PFSH remains a challenging benign neoplasm. Special microsurgical techniques and improved operative manipulation can improve surgical efficacy. PMID- 11775536 TI - CT scanning and arthroscopic evaluation of patellofemoral malalignment. AB - OBJECTIVE: To determine the pattern of malalignment and the extent of chondral damage, the patellofemoral joint was evaluated by CT scanning and the findings were proved by arthroscopic examination. METHODS: In 20 cases, 40 knees were examined by CT scanning with and without quadriceps contraction in order to differentiate between static and dynamic abnormalities. The CT images were analyzed. The arthroscopic examination was carried out for 27 knees in 20 cases. RESULTS: Ten knees had static patellar lateral subluxation and 16 knees dynamic lateral subluxation. Eleven knees had static patellar lateral tilt, and 7 knees dynamic tilt. All of the 27 knees showed arthroscopic patellar maltracking and chondral damage. CONCLUSIONS: The patellofemoral alignment, affection of quadriceps, and the extent of tight retinaculum may be precisely evaluated by CT measurement and proved by arthroscopic examination. PMID- 11775537 TI - Mechanism of ligustrazini against thrombosis. AB - OBJECTIVE: To investigate the mechanism of Chinese medicine ligustrazini against thrombosis, and the effects of ligustrazini on plasminogen activator inhibitor (PAI-1) expression in normal endothelial cells and lipopolysaccharide (LPS) stimulated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured by trypsin digestion method. PAI-1 protein in HUVEC conditioned medium was measured by Sandwich enzyme-linked immunosorbent assay (ELISA), and PAI-1 mRNA expression was determined by Northern blot analysis. Using electrophoretic mobility shift assay (EMSA), we observed HUVEC nuclear factor-kappa B (NF-kappa B) nuclear translocation. RESULTS: LPS treatment of cultured HUVECs resulted in a significant increase in PAI-1 protein and mRNA expression by these cells. However, when HUVECs were incubated with LPS plus ligustrazini, the upregulation of PAI-1 by LPS was abated. Moreover, ligustrazini could decrease the basal level of PAI-1 protein and mRNA in HUVECs as compared with control. Nuclear extracts prepared from HUVECs stimulated by LPS demonstrated that binding to the NF-kB oligo nucleotide increased as compared with the unstimulated cells, but ligustrazini did not change those binding in the absence or presence of LPS. CONCLUSIONS: Ligustrazini inhibited both basal and LPS-induced PAI-1 protein and mRNA expression in endothelial cells, and the modulation of PAI-1 in HUVECs by ligustrazini might have other mechanisms rather than NF-kB pathway. PMID- 11775538 TI - Computer-aided 3-D reconstruction and measurement of the optic canal and intracanalicular structures. AB - OBJECTIVE: To reconstruct the human optic canal and its inner structures, and to provide detailed knowledge of this region for optic nerve decompression for further understanding on the pathologic mechanisms of indirect optic nerve injury. METHODS: Six optic canals and their inner structures were reconstructed using a computer-aided 3-dimensional reconstruction system. Quantitative measurement of the canal wall thickness, bony canal transverse area, optic nerve transverse area, dural sheath transverse area, subarachnoid space transverse area, and subarachnoid space volume were done by means of the computer morphometric analysis system. The detailed spatial relationship among intracanalicular structures were also carefully identified on the 3-D models. RESULTS: The thinnest portion of the canal was the middle part of the medial wall (0.45 +/- 0.35 mm) and the narrowest space was in the middle part of the optic canal (the transverse area was 18.21 +/- 2.50 mm2). The volume of subarachnoid space which can be considered the compensatory space for distention incurred by the hemorrhage, optic nerve edema, or hematoma was 21.16 +/- 4.31 mm3. At the cranial opening, the middle part and orbital opening, its transverse area was 4.45 +/- 1.12 mm2, 2.68 +/- 1.32 mm2 and 1.23 +/- 0.83 mm2, respectively. CONCLUSIONS: Since the compensatory space was limited, even a tiny amount of blood or swelling of the nerve may cause optic nerve compression. Because the narrowest space was in the middle part of the optic canal and the compensatory space for distention gradually decreases from cranial end to orbital end, the middle part and the anterior part of the optic canal and dural sheath are critical in optic nerve decompression. PMID- 11775539 TI - Platelet-derived growth factor and basic fibroblast growth factor immunolocalized in proliferative retinal diseases. AB - OBJECTIVE: To study the role of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in the development of proliferative vitreoretinopathy (PVR). METHODS: Immunohistochemical localization was performed on frozen sections of the epiretinal or subretinal membranes from 21 PVR patients using! monoclonal antibodies against PDGF and bFGF and the streptavidin peroxidase system. RESULTS: PDGF was expressed in 15 of 21 specimens (71.4%), and bFGF was expressed in 14 specimens (66.7%). Different cell density was seen in different types of epiretinal membranes. The cell density of vascular membranes induced by PDR and Eales disease was the highest (> or = 61 cells/field, x 1000); nonvascular membranes induced by PVR or traumatic PVR had moderate cell density (31-60 cells/field); and the macular membrane had the lowest cell density (< or = 30 cells/field). CONCLUSION: The presents of PDGF and bFGF in PVR tissues suggest that PDGF and bFGF may play an important role in the development of PVR. PMID- 11775540 TI - Prognostic factors and therapeutic efficacy of combined radio-chemotherapy in Waldeyer's ring non-Hodgkin lymphoma. AB - OBJECTIVE: To improve the prognosis and therapeutic efficacy of Waldeyer's ring non-Hodgkin lymphoma (NHL-WR), combined radio-chemotherapy was used to treat the patients with NHL-WR and prognostic factors were analyzed. METHODS: Ninety patients with stage I-IV NHL-WR were treated with combined radio-chemotherapy. 4000 cGy to 6000 cGy were given to Waldeyer's ring structure and involved cervical nodes. Uninvolved low cervical nodes received 3000 cGy to 4000 cGy. The combination chemotherapy consisted of COPP (cyclophosphamide [CTX], vincristine [VCR], procarbazine [PCZ], prednisone [PDN]) or CHOP (CTX, ADM, VCR and PDN). Univariate analysis was performed to determine the prognostic unfavorable factors. RESULTS: Five-year overall survival rate was 69.7% for the whole group, and 83.2% for patients with stage I, II. In univariate analyses, over survival (OS) rates of the patients with low and intermediate grade (76.1%), with stage I, II (83.2%), without fever (75.2%) and with performance status (PS) 0, 1 (85.7%) were significantly better than those of the patients with high grade (53.0%), with stage III, IV (24.7%) with fever (38.5%), with PS2 (41.7%), PS3, 4 (0.0%), respectively (P < 0.05). CONCLUSIONS: Combined radio-chemotherapy can improve the 5-year survival rate for the patients with NHL-WR, especially for stage I, II patients. PS > or = 2, stage III, IV, fever and high grade histology were associated with unfavorable prognosis. PMID- 11775541 TI - Chemical conjugation of a novel antibody-interleukin 2 immunoconjugate against c erbB-2 product. AB - OBJECTIVE: To develop a new chemical method to produce a monoclonal antibody (MoAb) 520C9/recombinant human interleukin 2 (rhIL-2) conjugate. METHODS: MoAb 520C9 reactive with the protooncogene c-erbB-2 product P185 was chemically conjugated with rhIL-2 by using a simple two-step method. First, the rhIL-2 was activated by Sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate, a heterobifunctional linker, and N-succinimidyl s-acetylthioacetate was introduced onto 520C9. Then SATA on the 520C9 was reacted with the maleimide group on the activated rhIL-2 to generate 520C9-rhIL-2 immunoconjugate. RESULTS: The immunoconjugate retained the antigen binding activity compared to the respective native antibody as determined by an indirect live cell binding assay. The immunoconjugate also possessed IL-2 activity as measured by the standard CTLL-2 cells proliferation assay and the stimulation of human peripheral blood mononuclear cells (PBMCs) into lymphokine-activated killer cells. CONCLUSION: Our method of conjugation of rhIL-2 to 520C9 preserves the binding activity of the antibody and the cytokine function of IL-2. This simple and efficient method of conjugation should be applicable to other types of MoAbs and recombinant cytokines. PMID- 11775542 TI - Asymmetry of brain functional activation: fMRI study under language and music stimulation. AB - OBJECTIVE: To determine the asymmetry of the human brain functional activation. METHODS: With the help of GE Signa Horizon MRI system, 14 cases of right-handed volunteers were examined and the blood oxygenation level dependent method was used. The T1-weighted images were obtained with spin echo pulse sequence and the functional imaging (T2*-weighted) was performed using a single shot echo planar imaging pulse sequence. Data analysis was done with Sun Sparc Workstation and by the method of student t test or correlation analysis. RESULTS: Most of activation areas were in the left hemisphere under language stimulation, while they were in the right side under music stimulation. Besides, a few brain areas in the contralateral cerebral cortex were also activated under both stimulations. CONCLUSION: The present study supported the hypothesis of the asymmetry of brain functional activation and many brain areas of the cerebral cortex as well as both hemispheres worked in coordination. In addition, it also proved that fMRI is a feasible method in the study of human brain in vivo. PMID- 11775543 TI - Decreased bone mineral density in female patients with systemic lupus erythematosus after long-term administration of Tripterygium Wilfordii Hook. F. AB - OBJECTIVE: To investigate the possible bone changes in female patients with systemic lupus erythematosus (SLE) induced by long-term administration of Tripterygium Wilfordii Hook. F (TW). METHODS: 70 female SLE patients were divided into 4 groups according to their drug history: SLE disease control group, corticosteroids treatment group, TW treatment group, and both corticosteroids and TW treatment group. Bone mineral density (BMD) of the lumbar spine 2-4 and biochemical markers of bone turnover were studied. RESULTS: Long-term administration of TW could significantly decrease BMD levels in female SLE patients (P < 0.05). The patients receiving TW for more than 5 years had significantly lower BMD levels compared with those for less than 5 years. The degree of decreased BMD induced by TW was less severe compared with that of prednisone. No significant differences were observed in the biochemical markers of bone turnover among four groups (P > 0.05). CONCLUSION: Long-term administration of TW could decrease BMD levels in women. Osteoporosis may be an important problem for SLE patients treated with TW. PMID- 11775544 TI - P16 overexpression in pituitary adenomas studied by immunohistochemistry and in situ hybridization. AB - OBJECTIVES: To examine the expression of p16 gene and the clinicopathological characteristics of 31 pituitary adenomas. To investigate the relationship between p16 expression and cell proliferative activity by analyzing the expression of proliferating cell nuclear antigens (PCNA). METHODS: Immunohistochemistry and in situ hybridization were performed on freshly-prepared paraffin-embedded specimens of 31 pituitary adenomas. RESULTS: Varying degrees of overexpression of the p16 gene was found in the tumors specimens. A higher proportion of p16 positive tumor cells was associated with bigger size, more frequent invasion and higher recurrence of the tumors. The expression of p16 was found to be significantly associated with the degree of PCNA expression. CONCLUSION: Though inactivation of the p16 gene is known in wide range of tumors, our study suggested that p16 overexpression might play a role in the development and progression of pituitary adenomas. PMID- 11775545 TI - Co-modification of IL-2-TNF alpha fusion gene and B7.1 gene to murine breast tumor cells leads to improved tumor rejection and vaccine effect. AB - OBJECTIVE: To improve the vaccine potency of gene-modified tumor cells. METHODS: Using recombinant adenoviruses, we expressed the B7.1 gene in murine breast tumor cell line EMF6 and a subline previously transfected with retrovirus vector XdF harboring the IL-2-TNF alpha fusion gene. RESULTS: Immunization/challenge experiments demonstrated that IL-2-TNF alpha/B7.1 co-modified tumor cells possessed a lower tumorigenicity in vivo and an improved tumor-specific vaccine potency compared with single gene transfectant (P < 0.05). Three weeks after immunization with a variety of tumor cells, the mixed lymphocyte and tumor cells reaction assay (MLTB) and 51Cr-release assay were performed to test cellular immunity function. The results indicated that IL-2-TNF alpha and B7.1 together induced a more potent antitumor immune response than either molecule alone, 25% higher than IL-2-TNF alpha and 20% higher than B7.1, respectively. CONCLUSION: The IL-2-TNF alpha fusion gene and B7.1 gene act in concert to improve their antitumor effectiveness. PMID- 11775546 TI - Identification of a mutation hotspot in exon 8 of Wilson disease gene by cycle sequencing. AB - OBJECTIVE: To screen for mutation hotspot of Wilson disease (WD) gene in Chinese population. METHODS: Cycle sequencing was used to detect mutation in exon 8 of WD gene in 30 patients with Wilson disease. RESULTS: The same missense mutation, Arg779Leu, was identified in 14 WD patients, four of whom were homozygous and the other heterozygous for this mutation. The frequency of this mutation in Chinese patients was 30%. CONCLUSION: The codon 779 (CCG-->CTG) of exon 8 of WD gene was one of mutation hotspots in Chinese. PMID- 11775547 TI - Heat shock proteins mRNA expressions by peripheral blood mononuclear cells in asthma and chronic bronchitis. AB - OBJECTIVE: To investigate the manifestations that heat shock proteins(HSPs) possess in the pathogenesis of asthma and chronic bronchitis. METHODS: Using reverse transcription-DNA polymerase chain reaction (RT-PCR), we investigated the expression levels of HSP70, HSP90 alpha and HSP90 beta genes in peripheral blood mononuclear cells(PBMC) at natural state and after heat shock in 14 healthy volunteers, 21 patients with asthma and 18 patients with chronic bronchitis. RESULTS: No HSP70 gene but HSP90 alpha and HSP90 beta expressions were found in non-heat-shocked PBMC of normal control; HSP90 alpha and HSP90 beta genes may be expressed in PBMC of patients no matter whether they were in acute episode or not. Expression of HSP70 was found in PBMC of patients in acute episodes and of three symptoms-free patients with Aas 3, step 2. No expression of HSP70 gene was found in PBMC of patients in convalescent period but in PBMC of patients in acute episode. HSP90 alpha and HSP90 beta genes were expressed in PBMC of the two patients groups; After heat shock, expressions of the three genes increased in amount significantly in PBMC of all normal controls and patients. CONCLUSION: Expression of HSP70 gene in PBMC of asthmatic patients and chronic bronchitis was different, indicating that HSPs, especially HSP70 might be involved in the pathogenesis of asthma. PMID- 11775548 TI - Antifungal therapy for treatment of cryptococcal meningitis. AB - OBJECTIVE: To compare the curative effects of three different antifungal regimens in the treatment of cryptococcal meningitis. METHODS: Twenty-two patients were divided into 3 groups: Group I was given intravenous amphotericin B alone or combination with flucytosine therapy. Group II received intravenous fluconazole alone or combination with flucytosine. The treatment of Group III was divided into two steps, where the patients received intrathecal amphotericin B plus intravenous amphotericin B with or without intravenous fluconazole until the mycological culture of cerebrospinal fluid (CSF) turned negative, followed by oral fluconazole or itraconazole as maintenance therapy until direct microscopic examination of CSF showed negative once a week for three consecutive weeks. RESULTS: Of the twenty-two patients, 17 (77.3%) were cured, 2 (9.1%) improved, 3 (13.6%) died, and one (4.5%) relapsed. Of the 8 patients in Group I, 5 were cured, 2 improved, one died and one relapsed; Of the 4 patients in Group II, 2 were cured, and 2 died; All the 10 patients in Group III were cured without any recurrence. CONCLUSION: The two-step therapeutic regimen may be suited to the treatment of cryptococcal meningitis. PMID- 11775549 TI - Detection of Chlamydia pneumonia DNA in nasopharyngolaryngeal swab samples from patients with rhinitis and pharyngolaryngitis with polymerase chain reaction. AB - OBJECTIVE: To assess the prevalence of Chlamydia pneumomia DNA in patients with otolaryngic disease. METHODS: PCR assay was used to detect Chlamydia pneumonia specific Pst I 474 fragment DNA in swabs from patients with acute or subacute pharyngolaryngitis or rhinitis and sinusitis. C. pneumonia specific antibodies in sera were also assayed with microimmuno-fluoresence (MIF). RESULTS: About 28% (49/175) of the patients were PCR positive and 25.7% (45/175) were MIF antibodies positive. The accordance rate of the two methods was 91.8%. CONCLUSION: It is suggested that the C. pneumonia infection was common in this group of patients and the C. pneumonia Pst I 474 specific PCR was sensitive and specific for detecting C. pneumonia in pharyngolaryngitis or rhinitis and sinusitis. PMID- 11775550 TI - Localized amyloidosis of cervical lymph nodes. PMID- 11775551 TI - Molecular genetic analysis of a Chinese patient with Fabry disease. PMID- 11775552 TI - Granulomatous slack skin: a case of unusual variant of mycosis fungoides. PMID- 11775553 TI - Effects of resveratrol on oxidative modification of human low density lipoprotein. AB - OBJECTIVE: To determine the antioxidative effects of resveratrol (RES), a polyphenolic compound in red wine, on the oxidation of human low density lipoprotein (LDL) using two different oxidation systems. METHODS: Oxidation of LDL was induced by adding either Cu2+ or an azo compound. The extent of LDL modification was assessed by measuring the formation of thiobarbituric acid reactive substances (TBARS), the relative electrophoretic mobilities (REM), and the amount of oxidized LDL degradation by macrophages. RESULTS: During Cu(2+) induced oxidation, RES reduced TBARS formation in LDL by 70.5%, REM of LDL by 42.3% and the amount of macrophage degradation by 65.7%, respectively. The lag phase of LDL oxidation was also delayed by adding RES both in the copper ion and azo compound-induced oxidation systems. CONCLUSION: RES can protect LDL against both Cu(2+)-induced and azo compound-initiated oxidative modification in vitro, which might be due to its free radical scavenging capacity. PMID- 11775554 TI - Utilizing the child abuse potential inventory in a community health nursing prevention program for child abuse. AB - The objectives of this study were to: (a) Determine the potential for child abuse among the Joint New Parent Support Program Hawaii (Joint NPSP) client population, (b) Determine whether client participation in this program can reduce the potential for child abuse, and (c) Determine what client demographics correlate with the potential for child abuse. Joint NPSP is a prevention program for child abuse, screening all pregnant military families in Hawaii. The instrument used in this study was the Child Abuse Potential Inventory (CAP), a reliable and valid instrument used in the screening of physical child abuse. The CAP was completed by 142 pregnant Joint NPSP patients, ages 13-40 years, at the beginning of service provision and approximately 16 months later. Statistical measures used in analyzing the data were the t test and analysis of variance (ANOVA). Paired t tests were used to compare pre- and postprogram scores. Relations between the demographic profile information and CAP scores were analyzed with multiple regression analysis to identify risk factors for high child abuse. Out of 142 surveyed, 77 scored > 166 (signal detection) on the pretest abuse scale, and 65 scored < 166. In the > 166 group the pretest mean was a score of 257, and the posttest mean was 137. T-test results in the > 166 group were highly significant at .0001 on the scales of abuse, distress, rigidity, unhappiness, problems with family, and problems with others. ANOVA results in the > 166 group revealed a significant difference between an elevated abuse scale and patients with psychiatric problems (.0485), relationship problems (.0452), and past or present spouse abuse (.0421). This study validated that Joint NPSP is servicing a population at risk for child abuse potential. After intense home visitation by the community health nurses, the scores for child abuse potential decreased. A major limitation was the lack of a control group, the problem of maturation and history, and the possibility of regression toward the mean in scores. These limitations should be addressed in future studies with the use of 2 treatment modalities. Results highlight the need for focusing on relationship and spouse abuse issues in a military population. PMID- 11775555 TI - Physical illness: social construction or biological imperative? AB - All cultures have metaphors for mental illness that define how it is diagnosed, treated, and experienced by the patient. Cultural metaphors that define mental illness have been traced predominantly to biomedical and systems models. However, the research on factors such as progression of illness, survival rates, adherence to medical regimens, level of disability, and experience of pain in chronic and acute life-threatening illnesses suggests another metaphor. This article not only explores how a constructivist metaphor makes sense of this research, but also suggests an approach to consider in helping patients and their families deal with the difficult life circumstances that illness imposes. Implications for nurses are outlined. PMID- 11775556 TI - Using cognitive theory to improve nurse practitioners' anticipatory guidance with contraceptive pill users. AB - Community health nurse practitioners are often the major contraceptive counselors who may use anticipatory guidance to help clients' use behaviors. Because pregnancy rates during typical use are much higher than during "perfect" use, more effective anticipatory guidance could help improve use behaviors. Principles of cognitive theory were used to explore the implications of specific words and approaches associated with discussing young adults' contraceptive use. Qualitative results are reported here, and potential implications are made for nurse practitioners' anticipatory guidance related to contraceptive use. PMID- 11775557 TI - Transcending the suffering of AIDS. AB - The overall purpose of this qualitative study was to describe how patients with AIDS (PWAs) transcend the emotional and physical suffering of their illness. Content analysis of the interviews of 5 PWAs resulted in 3 main themes: creating a meaningful life pattern, connectedness, and self-care. The results of this study provide presumptive evidence that PWAs can transcend the suffering associated with a life-threatening illness and live meaningful and productive lives. Nurses who anticipate actual and potential growth in PWAs will be able to validate such experiences and feelings and encourage further development. PMID- 11775558 TI - Posthospital home care for frail older adults in rural locations. AB - After discharge from the hospital, older patients often require continued home care, including both professional and nonprofessional services. These needs can be exacerbated by health status (i.e., frailty) and geographic residence (i.e., rurality). It was the purpose of this study to examine patterns of postdischarge home care and outcomes for frail elders from rural locations. Seventy frail older adults being discharged from an acute urban-based hospital to home in a rural setting were recruited. Baseline data were collected before discharge from the hospital, and then calls were made at 48 hr and 2 and 4 weeks after discharge to evaluate use of resources and out-of-pocket expenses. Nonprofessional services were used most frequently, and the most intense time of use was at the 2-week postdischarge period. These findings suggest that discharge planning should include obtaining information about availability of both professional and nonprofessional services in the home community and arranging for appropriate delivery of both. PMID- 11775559 TI - Update. Surveillance of healthcare workers exposed to blood/body fluids and bloodborne pathogens: 1 April, 2000 to 31 March, 2001. PMID- 11775560 TI - How much weight loss is sufficient to overcome major co-morbidities? PMID- 11775561 TI - Assimilation. PMID- 11775562 TI - Prophylaxis of venous thromboembolism using two different doses of low-molecular weight heparin (nadroparin) in bariatric surgery: a prospective randomized trial. AB - BACKGROUND: Obese patients undergoing bariatric surgery are at a high risk of developing fatal pulmonary embolism or post-thrombotic syndrome. The prophylactic use of low molecular weight heparins (LMWHs) is correlated with a significant reduction in post-operative venous thrombosis in patients undergoing orthopedic or general surgery. In morbidity obese patients, the limited number of comparative trials are too sparse to allow a consensus on the effective dose and dosing schedule. METHODS: In a prospective study to evaluate the effect of two doses of nadroparin as prophylaxis for venous thromboembolism following bariatric surgery, 60 consecutive patients undergoing Rouxen-Y gastric bypass were randomized to receive either 0.6 ml (5700 IU) or 1.0 ml (9500 IU) of nadroparin started pre-operatively and then given once daily post-operatively until discharge. RESULTS: No statistically significant differences between the two groups were detected in any of the measured coagulation parameters either preoperatively or at days 1,3 and 5 postoperatively. No thrombotic events were observed pre- or post-operatively, and no patient developed meta-thrombotic syndrome at the 3 and 6 months follow-up. No bleeding events occurred in the patients given the lower dose compared with two major hemorrhages in those given the higher dose. CONCLUSION: Our results indicate that 0.6 ml (5700 IU) of nadroparin once daily is safe and well-tolerated, and it is as effective in prophylaxis of venous thromboembolism as the higher dose of 1 ml (9500 IU), in such high risk patients. PMID- 11775563 TI - Medical school curricula do not address obesity as a disease. AB - BACKGROUND: Obesity and its associated comorbidities have become an epidemic. However, medical school curricula do not address obesity as a disease. We undertook this study to assess medical students' knowledge about obesity before and after exposure to bariatric surgery. METHODS: A 10-item questionnaire that assesses knowledge of etiology, comorbidities, diagnosis, and management of obesity was mailed to all 201 2nd and 3rd year medical students enrolled in USF between 1999-2000. Data are mean +/- sem. Means were compared using t-test; p < or = 0.05 was significant. RESULTS: The overall response rate was 80%. The 3rd yr students who rotated on bariatric surgery (n = 24) answered correctly more questions than 55 students who did not rotate (90 +/- 2% vs 79 +/- 2%, p = 0.048). These differences were mainly noted in questions related to clinical management of obesity (p = 0.04). There were no significant differences among responses from 2nd yr students (n = 81) and the subset of 3rd yr students (n = 55) who did not rotate through bariatric surgery. CONCLUSIONS: Medical students' knowledge about obesity is significantly improved by rotation on a bariatric surgery program and not during rotations on other clinical disciplines. Medical school curricula should be changed to reflect the growing epidemic of obesity and enhance students' knowledge about obesity as a disease. PMID- 11775564 TI - Reduction in psychopathology following bariatric surgery for morbid obesity. AB - BACKGROUND: Although there has been some disagreement, there is growing evidence now that psychopathology is a comorbidity of morbid obesity among patients seeking bariatric surgery. The aim of this study was to determine whether psychopathology decreases following this surgery. METHODS: Utilizing a national sample, this study focused on pre- and post-surgery scores on the Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2). The MMPI-2 was administered first during the pre-surgery medical examination, and again between 6 months and 1 year following surgery. RESULTS: Validity scale scores on the pre- and post-surgery MMPI-2s indicated that there was no impediment to interpreting the clinical scale scores of these tests. There was a pervasive pattern of statistically significant decreases in pre- to post-surgery clinical scale scores. Further, comparison of MMPI-2 clinical scale scores to available test norms showed that the number of participants showing signs of mental disorders was unusually high before surgery, and at or below the test norms following surgery. CONCLUSIONS: There is clear evidence in this study that psychopathology declines following bariatric surgery. The unusually high levels of psychopathology before surgery may be a joint function of the factors producing the morbid obesity, and a reaction to the obesity itself. That psychopathology declines following surgery to levels expected in the general population indicates that the patients were becoming more positive about their lives. PMID- 11775565 TI - Glucose disposal in morbidly obese patients in the early post-operative period. AB - BACKGROUND: In surgical patients, operative stress causes protein catabolism, muscle mass loss, and impaired glucose tolerance. We investigated fuel metabolism and glucose and protein turnover in 15 obese subjects who underwent biliopancreatic diversion (BPD) by using stable labelled isotopes. METHODS: 6 males and 9 females (age 45.11 +/- 8.9 years, BMI of 48.85 +/- 4.43 kg/m2) who underwent BPD were studied, and the APACHE II score was calculated. Patients were studied 3 times (before BPD, 1st and 3rd postoperative day). Glycemia was stable- maintained by continuously infusing Rapid insulin. Each day of the study, the patients received a primed, constant infusion of [15N2] urea, and, 180 min after, a [6.6-2H] glucose infusion started and continued for 3 hours. Indirect calorimetry was performed during the study, under TPN (30 kcal/kg). RESULTS: The APACHE score was lower on the 3rd postoperative day than on the 1st postoperative day (7.4 +/- 2.7 vs 6.3 +/- 2.6, p < 0.05). The npRQ was different throughout the post-operative period (0.82 +/- 0.03 vs 0.9 +/- 0.06, p < 0.05), while urinary nitrogen excretion, energy expenditure and glycemia did not change. The insulin amount infused was lower during the 3rd post-operative day (44.25 +/- 12.3 vs 64.12 +/- 11 UI on the 1st one, p < 0.05). Insulinemia was lower during the 3rd than during the 1st postoperative day (66.4 +/- 9.49 vs 117.44 +/- 8.49 microU/ml, p < 0.05). Non-essential fatty acid levels were higher on the 3rd post operative day than on the 1st one (0.98 +/- 0.6 vs 0.45 +/- 0.34 mmol/L, p < 0.01). No differences were observed in glucose and urea turn-over. CONCLUSION: The metabolic pattern of morbidly obese patients operated by BPD was similar to that of other critically ill patients previously studied in the literature. Furthermore, the increased glucose oxidation rate observed on the 3rd post operative day was coupled with an improved clinical condition. PMID- 11775566 TI - Serum leptin levels after bariatric surgery across a range of glucose tolerance from normal to diabetes. AB - BACKGROUND: A longitudinal, clinical intervention study with bariatric surgery was done to investigate the relationship between leptin levels, BMI, and insulin during weight loss across a range of glucose tolerance from normal to diabetes. METHODS: 43 morbidly obese patients (BMI: 42-75 kg/m2) undergoing vertical banded gastroplasty Roux-en-Y gastric bypass (VBG-RGB), were divided into 3 groups: 21 normal (NGT), 12 impaired glucose tolerance (IGT) and 10 type 2 diabetes (DM). Leptin, insulin, glucose, lipids and uric acid were measured at baseline and 2, 4, 6, and 12 months following surgery. RESULTS: BMI fell from 54.1 +/- 9.1 to 34.6 +/- 6.3 kg/m2, similarly in all groups. Leptin decreased from 73.9 +/- 8.7 to 16.9 +/- 10.2 ng/ml and was strongly correlated with BMI during 1-year follow up (r = 0.78; p < 0.001). Linear univariate analysis for repeated evaluation showed a positive correlation between leptin and glucose, triglycerides, uric acid, and insulin. Multivariate regression analysis indicated that BMI was independently correlated with the decrease in leptin (p < 0.001), accounting for 66% of the variance in leptin levels during weight loss. These results were found in the NGT and IGT groups. In the DM group, a small additional influence in leptin levels was attributed to glucose decrease. CONCLUSIONS: A strong link between leptin and BMI was found after surgery. BMI was the main determinant of the decrease of leptin. In these patients submitted to bariatric surgery, ranging from normal glucose tolerance to diabetes, changes in insulin levels and metabolic parameters, except for glucose in the DM group, did not appear to be correlated with changes in leptin levels. PMID- 11775567 TI - Band erosion: incidence, etiology, management and outcome after banded vertical gastric bypass. AB - BACKGROUND: Prosthetic devices have been used in bariatric operations to control the outlet of the gastric pouch and thus maintain weight loss. A complication of these prostheses is erosion or migration into the gastric lumen. The transected banded vertical gastric bypass (TBVGBP) is one of the modifications of gastric bypass. This modification has a silastic ring placed around the pouch to form the stoma. METHOD: The records of patients with band erosion (BE) after this operation were reviewed, to determine the incidence, etiology, management and outcome during a 9-year period. RESULTS: From May 1992 through May 2001, 2,949 primary and secondary TBVGBP were performed through the Center for Surgical Treatment of Obesity, utilizing 3 hospitals. 48 patients (1.63%) were documented to have BE: 40 documented by us and 8 by subsequent treating surgeons or at other facilities. Presenting symptoms were weight regain (18), stenosis or obstruction (17), pain (9), bleeding (7), and 5 were incidental findings. Some patients presented with more than one symptom. 8 were treated expectantly with spontaneous extrusion of the band. 16 bands have been removed endoscopically in 14 patients. 26 patients had open surgical revision, with 12 having band removal only and 14 band removal and revision of either the gastroenterostomy with or without band replacement or conversion to a distal Roux-en-Y gastric bypass (DRYGBP). Two patients who had revision to DRYGBP were re-revised to a longer common limb because of protein malnutrition. Three patients who had revision of the gastroenterostomy with band removal and replacement developed leaks that were managed non-surgically. Two of these re-eroded and the band was removed endoscopically with a subsequent revision to a DRYGBP. There was no death due to BE. CONCLUSION: BE is an uncommon complication of TBVGBP. Infection, previous bariatric operations and surgical technique play a role in BE. BE is best managed by endoscopic removal but can be treated expectantly or by open surgical intervention. Band removal without replacement or revision to DRYGBP may result in weight regain. PMID- 11775568 TI - Quality of life after the Magenstrasse and Mill procedure for morbid obesity. AB - BACKGROUND: The authors assessed the quality of life (QOL) of patients after the Magenstrasse and Mill (M-M) procedure for morbid obesity (MO) and compared this with the QOL of MO patients and non-obese controls. METHODS: Personal, postal and telephone questionnaire survey was completed by 82 patients after the M-M procedure, 35 MO patients and 20 normal controls. QOL was assessed by Short Form 36 (SF-36), Hospital Anxiety and Depression (HAD) scale, and obesity surgery related questionnaire. RESULTS: Physical, social and psychological well-being of patients was substantially better after the M-M compared with their MO counterparts. After the M-M procedure, patients were significantly less depressed but remained anxious when compared with morbidly obese patients. The majority of patients (88%) were pleased with the result of surgery. CONCLUSION: This study provides empirical evidence that the M-M procedure for MO leads to a substantially better QOL. PMID- 11775569 TI - The role of psychological functioning in morbid obesity and its treatment with gastroplasty. AB - BACKGROUND: The authors evaluated the psychological characteristics of the morbidly obese. The condition-specific and quality-of-life characteristics of a large sample of vertical banded gastroplasty (VBG) patients were evaluated. The role that these psychological characteristics play in moderating the success of gastroplasty surgery, as well as the impact of surgery on quality of life, was examined. METHODS: This is a cross-sectional evaluative study of a clinical samples, with longitudinal follow-up and with non-surgical comparison groups. 89 morbidly obese individuals were assessed before VBG (but after having been accepted for surgery) and again 1.27 years after surgery. This group represents 98% of the patients who received VBG (i.e., a 2% dropout rate). We used established psychological measures (quality of life, adjustment to obesity, functional impairment, and eating attitudes), including a scale developed by our group specifically for morbid obesity, to identify distinct psychological profiles of the morbidly obese before surgery. RESULTS: The three profile groups differed significantly in psychological characteristics, ranging from high functioning (little emotional distress, functional impairment or dysfunctional eating) to poor functioning (high emotional distress, functional impairment and dysfunctional eating). The subgroups did not differ on pre-surgical weight, and did not differ from morbidly obese groups not seeking surgery. For the surgery group, regardless of pre-surgery psychological profile, VBG produced significant weight loss, maintained at 1 year after surgery. As well, surgery resulted in significant improvements in quality of life and psychological adjustment, especially in the profile group initially presenting with psychological disturbance. CONCLUSION: There was no evidence to suggest that those with pre surgical psychological difficulties did more poorly with VBG. These data call into question screening out individuals with psychological problems from gastroplasty surgery. Furthermore, psychological difficulties, if they exist, appear more related to the nature of morbid obesity than to the character of the individual. Psychological difficulties pre-surgery were normalized following surgery. PMID- 11775570 TI - Laparoscopic vertical banded gastroplasty--an effective long-term therapy for morbidly obese patients? AB - BACKGROUND: Vertical banded gastroplasty (VBG) has previously been documented as an effective treatment for morbid obesity. We have described a laparoscopic technique to perform this operation. Follow-up data are now presented. METHODS: A consecutive series of 139 morbidly obese patients were operated on with laparoscopic VBG. The patients were assessed with respect to peri- and postoperative morbidity, postoperative recovery and weight reduction up to 5 years thereafter. RESULTS: Conversions to an open operation (n = 6) and early reoperations (n = 3) occurred in the early part of the series. Late complications were observed in 8 patients. The average weight reduction after 1 year was 50% of excess body weight, which remained also after 2 years. The continued follow-up covering 3 to 5 years postoperatively revealed a moderate weight gain in about 20% of patients. CONCLUSION: VBG can be safely performed by use of the laparoscopic technique. The average weight reduction after 1 and 2 years was 50% of excess body weight, whereafter tendency to partial weight gain was noted, suggesting an outcome comparable to that documented after the open surgical approach. PMID- 11775571 TI - Conversion of failed vertical banded gastroplasty to open adjustable gastric banding. AB - BACKGROUND: Occasionally, patients with failed vertical banded gastroplasty (VBG) present for secondary treatment. We performed the reoperations using adjustable gastric banding (AGB) technique. METHODS: From 1991 to 1997, 80 morbidly obese patients underwent VBG. In 7 (8.7%), staple-line disruption and weight regain were detected within 2 years of follow-up. Conversion to AGB was performed between 1994 and 1998. Meanwhile, another 80 morbidly obese patients underwent primary open AGB. RESULTS: In the 7 patients, staple-line disruption was seen on radiography as a leak of contrast material across the gastric partition. After conversion of "failed" VBGs to AGB, postoperative results have been very satisfactory and similar to those of the primary open AGB group. CONCLUSIONS: VBG is a safe technique, although conversion rates were significant. Staple-line disruption constituted the chief cause of insufficient weight loss and frequently indicated the need for further surgery. Our results of the revisional surgery confirm that the reoperations for failed VBG can be performed using AGB technique. PMID- 11775572 TI - Effects of adjustable gastric banding on altered gut neuropeptide levels in morbidly obese patients. AB - BACKGROUND: Patients with gastroesophageal reflux disease (GERD) have alterations of gut neuropeptides, such as neurotensin (N) and motilin (M), which are resolved following antireflux surgery. Obesity is associated with GERD. Since the adjustable gastric band prevents gastroesophageal reflux in morbidly obese patients, this study was performed to investigate plasma levels of N and M before and after adjustable gastric banding (AGB). METHODS: 47 morbidly obese patients were operated laparoscopically using the Swedish AGB. Pre- and postoperatively basal plasma levels of N and M were investigated. Symptoms such as heartburn, regurgitation and dysphagia were documented, and esophageal manometry as well as 24-hour pH-monitoring were performed pre- and postoperatively. 11 non-obese, asymptomatic, age-matched volunteers served as controls. RESULTS: After a median postoperative follow-up period of 268 days, a significant weight reduction was observed. Preoperatively, 14 patients suffered from reflux symptoms. An insufficient lower esophageal sphincter (LES) was found in 8 patients, and 2 patients had impaired esophageal body motility. Pathologic pH-testing was found in 6 patients. Postoperatively, reflux symptoms were present in 4 patients; LES findings and pH-testing were normalized in all patients. However, there was significant impairment of esophageal peristalsis. Preoperatively, levels of N were significantly decreased and levels of M increased compared with control subjects. Postoperatively, there was a significant increase of N and levels of M were normalized. Alterations in gut neuropeptides did not correlate with reflux symptoms, impaired gastroesophageal motility, age, gender or BMI. CONCLUSION: Morbid obesity alters gut neuropeptides, which are resolved by AGB. This may be caused by reduction of hypercaloric nutrition postoperatively rather than by improvement of gastroesophageal reflux. PMID- 11775573 TI - Bariatric Analysis and Reporting Outcome System (BAROS) following laparoscopic adjustable gastric banding in Finland. AB - BACKGROUND: The reporting on outcome following barlatric procedures should include changes in comorbid conditions and quality of life (QOL), in addition to weight loss. The Bariatric Analysis and Reporting Outcome System (BAROS) appears to provide the means to fulfill these requests. We have re-evaluated our previously published, initial results of laparoscopic adjustable gastric banding, using BAROS. METHODS: Our first 60 consecutive patients were treated laparoscopically between the years 1996 and 1999, using the Swedish Adjustable Gastric Band (SAGB). After a minimum follow-up of > or = 17 months (median follow up 28 months, range 17-61 months), a postal questionnaire concerning QOL, medical condition and excess weight loss (BAROS) was sent to the patients. In addition, the patients' opinion regarding the operation was evaluated as well as the extent that the band had caused the patients any of the more common side-effects. RESULTS: 87% of the patients returned the questionnaire properly answered. According to BAROS, the outcome was regarded as VERY GOOD in 12% of patients, GOOD in 38%, FAIR in 29% and FAILURE in 21%. Not one had an EXCELLENT outcome. 23% of the patients were disappointed with their operation. The incidence of band related side-effects was high. CONCLUSION: Our results are comparable with other published series including the learning curve. In our opinion, BAROS should be widely adopted. PMID- 11775574 TI - Lap-Band erosion: incidence and treatment. AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is an effective and safe surgical treatment for morbid obesity. Migration of the band through the stomach wall is a well-known late complication that may jeopardize the aim of the treatment--permanent weight reduction. METHODS: 301 patients were followed for > or = 2 years (mean 39 months) after a Lap-Band procedure. Cases of erosion were studied retrospectively. RESULTS: 5 patients (1.66%) developed erosions. Laparoscopic band removal was carried out in these 5 cases without complication. The first 4 have received a new Lap-Band, and all are doing well. CONCLUSION: Band erosion is a bothersome late complication after LAGB and requires band removal. Rebanding is a feasible option. Further study and longer follow-up are necessary to determine whether these patients will develop erosion again. PMID- 11775575 TI - 30% complications with adjustable gastric banding: what did we do wrong? AB - BACKGROUND: The authors analyzed the complications in patients following laparoscopic adjustable gastric banding (LAGB) for morbid obesity. METHODS: Retrospective analysis of the 36 LAGB patients was done. The operations were performed from December 1997 to the December 1999 using the Lap-Band. RESULTS: 11 complications occurred. Most common was port-site infection or port migration (5 patients). These complications were termed minor. In 3 patients, slippage of the gastric wall was observed, all corrected laparoscopically. In another 3 patients, removal of the band was necessary for poor patient compliance (1), for intussusception of the gastric wall through the band with occlusion of the stoma (1), and for infection of the band (1). These complications were termed major. The overall complication rate was 30.5%. CONCLUSION: Compared to the literature, our complication rate was rather high. Based on our analysis, the following measures are recommended: 1) antibiotic prophylaxis; 2) drainage of the port site; 3) proper band and port placement and fixation; 4) closer psychological evaluation and follow-up. By these measures, hopefully we can obtain better results in the future. PMID- 11775577 TI - Compulsive eating and gastric bypass surgery: what does hunger have to do with it? AB - BACKGROUND: Binge eating and other patterns of disordered eating in obese patients need further investigation. In a previous study by this author, one third of patients presenting for bariatric surgery met strict criteria for Binge Eating Disorder. It is important to clarify the role of such eating behaviors on outcome of surgery to determine whether treatments targeted specifically at these behaviors and associated psychological issues can improve surgical outcome. The aim of this paper is to raise awareness of the range of disordered eating patterns in bariatric patients, describe an approach used, and discuss issues reported by patients after surgery. METHODS: Patients completed questionnaires before surgery (QWEP, BES, BDI) and were seen for a pre-surgery mental health evaluation. High risk patients were identified and invited to attend a post surgery group (CBT approach) as a preventive measure to help them deal with eating patterns as well as emotional adjustment. RESULTS: Disordered eating patterns can persist after surgery. While surgery may decrease actual physical hunger and reduce physical capacity for food, it is still possible to eat compulsively, although the patterns may change somewhat due to the surgical procedure. CONCLUSION: Since long-term weight maintenance depends on post operative changes in eating behaviors, it is important to identify patients at risk for a range of disordered eating patterns so that a comprehensive treatment plan that targets the eating disturbances and associated psychological components can be implemented. PMID- 11775576 TI - 60 reoperations on 890 patients after gastric restrictive surgery. AB - BACKGROUND: Since 1988 we performed gastric restriction operations on 890 patients; 60 required subsequent re-operation. METHODS: The Molina non-adjustable band was discontinued early because of a high percentage of re-operations. Between 1992 and 1995, we performed the Mason vertical banded gastroplasty (VBG) using a 9-cm long vertical staple-line, with a re-operation rate of 15%. Since 1996, we have been performing a 6-cm long vertical staple-line, with a re operation rate of 0.7%. The MacLean VBG also had a low re-operation rate (0.9%), but the seriousness of its most dangerous complication, perioperative cardia fistula, limited our use of this method to specifically selected cases. With adjustable banding, we have used the Swedish band which produced a low re operation rate (2.1%), consisting of relatively simple corrective procedures. RESULTS: The re-operations produced results similar to those of first-time operations in terms of weight loss and nutritional status. In particular, after 3 years, re-operated patients had similar weight to those who had been operated upon with the same method initially. CONCLUSIONS: When the surgical procedure was selected with greater astuteness and modified appropriately, the re-operation rate decreased from 17% in the period 1992 to 1995, to 1% in the period 1996 to 2000. PMID- 11775578 TI - Gastric schwannoma found incidentally 19 years after a horizontal gastroplasty for morbid obesity. AB - This report represents the first known case of a gastric schwannoma in a patient subsequent to a gastric stapling and partitioning procedure for morbid obesity. The submucosal tumor found in the collapsed distal portion of the stomach was merely an incidental finding and it appeared that all of the patient's ongoing symptomatology (nausea and vomiting after meals) was a reflection of the chronic obstruction that was present at the gastric partitioning staple-line. No correlation between gastric stapling and partitioning and the development of gastric schwannoma is known or is suggested in this report. PMID- 11775579 TI - Endoscopic fibrin sealing of high-output non-healing gastrocutaneous fistulas after vertical gastroplasty in morbidly obese patients. AB - BACKGROUND: Fibrin glue was used in a various fields of surgery during the last 15 years, but its use has not been reported in bariatric surgery yet. METHODS: In 2 out of 215 morbidly obese patients who underwent vertical banded gastroplasty, a non-healing gastrocutaneus fistula (GCF) developed. In both patients sepsis occurred, caused by a leak of the posterior gastric wall, which was managed by means of an unsuccessful reoperation. After that, sepsis recurred, and a non healing GCF developed. These GCF were managed endoscopically by the use of a fibrin sealant (Beriplast P 2 ml set, Behring) as a tissue adhesive. RESULTS: One injection was needed for the first case and six for the second in achieving full healing of the fistulas. No evidence of fistula was observed at gastroscopy 3 and 24 months after the end of therapy. CONCLUSIONS: Endoscopic use of human fibrin sealant is simple, safe, effective and in some cases life-saving. This is a therapeutic option in high output GCF in morbidly obese patients. PMID- 11775580 TI - Pouch dilatation after gastric banding causing gastric necrosis. AB - BACKGROUND: Early or late pouch dilatations account for a moderate complication rate after restrictive bariatric operations. Various strategies were developed to prevent or treat pouch dilatations. METHODS: A case of necrosis of gastric wall in a concentric dilated pouch following laparoscopic adjustable gastric banding is reported as a severe complication of a conservative treatment attempt. RESULTS: Emergency laparotomy resulted in band removal, partial gastric resection and prolonged hospital stay. CONCLUSION: Conservative strategies in the treatment of pouch dilatations bear the risk of complications, with both failure of the bariatric procedure and critical clinical course. Indication for early operative reintervention is recommended. PMID- 11775582 TI - First successful laparoscopic gastric band. PMID- 11775581 TI - Mini-gastric bypass controversy. PMID- 11775583 TI - Workshop: Anorexia during disease--from research to clinical practice. Ascona, Switzerland, September 10-15, 2000. PMID- 11775584 TI - Biophysics and Biology of Environmentally Important Membrane-Active Compounds. May 11-13, 2001. Wroclaw, Poland. Proceedings and abstracts. PMID- 11775585 TI - Alzheimer's disease, cancer and the search for a better aspirin. Postgraduate course at Mount Sinai School of Medicine, New York, NY June 22-23, 2001. PMID- 11775587 TI - Proceedings of the 4th International Workshop on Animal Locomotion. 24-26 May 2000. PMID- 11775586 TI - Sensitivity to Growth Hormone, Standardization of IGF-I Measurements. Proceedings of the 5th KIGS/KIMS Expert Meeting on Growth and Growth Disorders. Windsor, United Kingdom. February 2-3, 2001. PMID- 11775588 TI - Molecular, Cellular and Developmental Biology of Reproduction: Basic and Clinical Aspects. Proceedings of the XV Congress of the International Federation of Associations of Anatomists and the 4th International Malpighi Symposium. Rome, Italy, September 11-16, 1999. PMID- 11775589 TI - Asian Leprosy Congress. 9-13 November 2000, Agra, India. Proceedings and abstracts. PMID- 11775590 TI - Risk Assessment and Communication for Food Safety. Proceedings of the 1st Joint CSL/JIFSAN Symposium on Food Safety and Nutrition. 20-22 June 2000. PMID- 11775591 TI - XXVI Meeting of the Brazilian Society of Immunology. Campos do Jordao, Brazil. October 7-10, 2001. Abstracts. PMID- 11775593 TI - [Efficacy of a converting enzyme inhibitor in the prevention of recurrence of stroke]. PMID- 11775594 TI - Orthopaedic proceedings. 2001. PMID- 11775595 TI - Society of Critical Care Medicine 31st Critical Care Congress. San Diego, California, USA. January 26-30, 2002. Abstracts. PMID- 11775596 TI - Parkinsonism: onset, progression, and mortality. 1967. PMID- 11775598 TI - What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. PMID- 11775597 TI - Differential effects of D1 and D2 agonists in MPTP-treated primates: functional implications for Parkinson's disease. 1990. PMID- 11775599 TI - Clinical characteristics of a family with chromosome 17-linked disinhibition dementia-parkinsonism-amyotrophy complex. 1994. PMID- 11775600 TI - Newer drugs in the treatment of parkinsonism. 1951. PMID- 11775601 TI - Levodopa. Is toxicity a myth? 1998. PMID- 11775602 TI - A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in parkinsonism. 2000. PMID- 11775603 TI - Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson's disease. 2000. PMID- 11775605 TI - Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood. 1999. PMID- 11775604 TI - Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. 1998. PMID- 11775606 TI - Syndrome of acquired aphasia with convulsive disorder in children. 1956. PMID- 11775607 TI - Plasmapheresis in Rasmussen's encephalitis. 1996. PMID- 11775608 TI - Paroxysmal kinesigenic dyskinesia and infantile convulsions. Clinical and linkage studies. 2000. PMID- 11775609 TI - Intravenous diphenylhydantoin in treatment of acute repetitive seizures. 1968. PMID- 11775611 TI - Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. 1993. PMID- 11775610 TI - Quantitative hippocampal MRI and intractable temporal lobe epilepsy. 1995. PMID- 11775613 TI - Academy 2001. American Academy of Optometry annual meeting. December 6-10, 2001. Philadelphia, Pennsylvania, USA. Abstracts. PMID- 11775612 TI - Seizure frequency and the health-related quality of life of adults with epilepsy. 1999. PMID- 11775614 TI - 10th International Conference on Gene Therapy of Cancer. 13-15 December 2001. San Diego, California, USA. Abstracts. PMID- 11775615 TI - [Fitness for work and public health in hospital workers]. AB - Transmission of infection to patients from health-care workers has recently become a topic in medical literature. The Centers for Disease Control (CDC) and the Society for Healthcare Epidemiology of America (SHEA) in the US, and the UK Health Departments in the UK issued guidelines for professionals performing invasive procedures who may be infected with human immunodeficiency virus (HIV) or hepatitis B virus. The Italian Istituto Superiore di Sanita (ISS) in 1999 held a Consensus Conference advocating routine mandatory testing of health-care workers and a general restriction on performing exposure-prone invasive procedures. Nevertheless, the ISS failed to identify the institution that should be responsible for these controls. Harmful behavior of health-care workers comprises not only the risk of the impact of blood-borne infections but also the impact of, for example, depression, substance missuse, side effects of medication, family problems, fatigue or lack of insight. Time and effort is required for drafting, revising and refining policy in this area. The complexity of the matter hampers the standardisation of guidelines internationally: American and British policies are hardly enforceable in the Italian context. The Italian Study Committee for the Hospital Management of Workers affected by illnesses hazardous for the public (GIS GILMaPP) here discusses the legal end ethical issues surrounding the risk of "provider-to patient" transmission of disease. The policy dilemma involving patients' rights and sick workers should be addressed on a case-by-case basis. Strenuous efforts should be made to respect ethical and legal issues, such as informed consent, confidentiality, and to avoid discrimination. There is an urgent need for the medical community to find a broad consensus that would be acceptable for both the healthcare worker and the patient. PMID- 11775616 TI - 8th Bath Conference on Osteoporosis. December 5-7, 2001. Bath, United Kingdom. Abstracts. PMID- 11775617 TI - [Editorial. Lack of modern ophthalmologic technology in Romania]. PMID- 11775618 TI - [LIII Annual Meeting of the Spanish Society of Neurology. Barcelona, 13-15 December 2001. Abstracts]. PMID- 11775619 TI - Microscopy, Barcelona 2001. 4-7 September 2001. Abstracts. PMID- 11775620 TI - Abstracts from the 12th International Symposium on Amyotrophic Lateral Sclerosis/Motor Neuron Disorders. Oakland, USA, 18-20 November 2001. PMID- 11775621 TI - Value of echocardiographic findings in predicting cardiovascular complications in infective endocarditis. AB - Echocardiography allows the detection of vegetations and estimation of valvular dysfunction in patients with infective endocarditis. The value of echocardiographic findings in predicting cardiac and other vascular complications in infective endocarditis is not well understood. Identification of high-risk patients and early surgery may improve their prognosis. The authors reviewed echocardiographic findings and related them to the development of congestive heart failure, systemic embolism, and the need for surgery or the risk of death without surgery in patients with infective endocarditis. There were 125 episodes of endocarditis in 114 patients (84 episodes [67%] in men) with a mean age +/- standard deviation of 37 +/- 7 years. Vegetations were detected by echocardiography on at least 1 valve in 87 episodes (70%); on the mitral valve in 36 episodes (29%); on the aortic valve in 21 episodes (17%); and on the tricuspid valve in 45 episodes (36%). Severe aortic regurgitation was present in 9 episodes (7%) and severe mitral regurgitation in 4 instances (3%). In 12 of 21 episodes (57%) of vegetations on the aortic valve compared with 15 of 104 patients (14%) without vegetations on the aortic valve (p < 0.001), and in 8 of 9 instances (89%) of severe aortic regurgitation compared with 19 of 116 episodes (16%) without severe aortic regurgitation (p<0.00001), the patients developed congestive heart failure. In 18 of 55 episodes (33%) of vegetations on the aortic/mitral valve compared with 17 of 70 episodes (25%) without vegetations on the aortic valve/mitral valve (p = NS), the patients developed systemic embolism. In 13 of 21 episodes (62%) of vegetations on the aortic valve compared with 19 of 104 episodes (19%) without vegetations on the aortic valve (p < 0.001), and in 8 of 9 episodes (89%) of severe aortic regurgitation compared with 24 of 116 episodes (21%) without severe aortic regurgitation (p < 0.00001), the patients either had surgery or died without surgery. Echocardiographic findings do not reliably predict the risk of systemic embolism in patients with infective endocarditis. Vegetations on the aortic valve and severe aortic regurgitation detected by echocardiography predict a high risk of developing congestive heart failure, and for the combined outcome of requiring surgery, or dying without surgery in infective endocarditis. Early surgery may improve the outlook for survival of these patients. PMID- 11775622 TI - Platelet-dependent thrombin generation in patients with unstable angina pectoris. AB - Platelet-dependent thrombin generation was assessed during both unstable and stable periods in 59 patients with unstable angina and at rest in 31 healthy controls. Thrombin generation during the unstable period was significantly greater than that at rest in the healthy control group (p < 0.0001) and that during the stable period (p < 0.0001). Changes in thrombin generation were related to the time after onset of unstable angina, not to degree of improvement in the severity of coronary stenosis. PMID- 11775623 TI - tPA via infusion catheters followed by continuous IV infusion for 3 days prevents intimal hyperplasia after balloon injury. AB - A rabbit model was used to examine the effects of tissue plasminogen activator (tPA) on development of intimal hyperplasia following balloon injury. Thirty-two hereditary hypercholesterolemic (KHC) rabbits underwent percutaneous transluminal coronary artery balloon catheterization and injury to the common iliac artery, after which they were divided into four groups: untreated (control); Dispatch catheterized-30 minutes local saline delivery [D(+)-tPA(-)]; D(+)-30 minutes local tPA delivery (0.6 mg/kg) [D(+)-tPA(30 min)]; and D(+)-30 minutes local tPA + 3 days intravenous infusion (0.6 mg/kg/24 h) [(D(+)-tPA(30 min + 3 d)]. Twenty eight days later, the intimal cross-sectional areas of all three Dispatch catheterized groups were significantly smaller than those of control groups, as were the intimal/medial area ratios. Moreover, the intima/media ratios of the D(+)-tPA(30 min + 3 d) group were significantly smaller than those of the D(+) tPA(-) group. Thus, local delivery of tPA via Dispatch catheters followed by continuous intravenous infusion of tPA for 3 days prevented intimal hyperplasia after angioplasty. PMID- 11775624 TI - Effects of cardiac rehabilitation on atrial wave in patients after myocardial infarction. AB - Cardiac rehabilitation (CR) can improve cardiac hemodynamic performance in patients after myocardial infarction (MI). Little evidence is provided concerning the consequences of CR on atrial wave duration, and less is known about the link between pre-arrhythmogenic patterns and the cardiovascular performance improvement in these subjects. Twenty-six patients, post-MI 0 to 7 days, underwent a complete CR cycle and a signal-averaged electrocardiogram (SAECG) for the evaluation of atrial activation parameters (group 1) to appreciate if physical training can promote parallel improvement in cardiovascular and intra atrial conduction parameters. A control group of 24 well-matched nonischemic subjects (group 2) was chosen for data comparison. Resting heart rate (p < 0.01) and resting double product (p < 0.01) decreased after CR in groups 1 and 2, while diastolic blood pressure at maximal stress was decreased in group 1 (p < 0.01) with a parallel increase in the time of physical training (p < 0.05). SAECG parameters of atrial activation were unchanged in group 1 after the comparison and only total atrial duration activation (dA) reached statistical significance (113.3 +/- 17.2 msec vs 120.8 +/- 14.2 msec, subjects after CR vs before CR, p < 0.01). CR could improve intra-atrial activation in subjects after MI, but the consequences of hemodynamic adjustment of the trained heart must undergo a more accurate evaluation to verify if CR can prevent adverse arrhythmogenic complications of MI through cardiovascular performance improvement. PMID- 11775625 TI - Comparison of clinical echocardiographic and hemodynamic characteristics of male and female patients who underwent mitral balloon valvuloplasty. AB - The clinical echocardiographic and hemodynamic characteristics and outcome of male and female patients before and after valvuloplasty were evaluated. The study population consisted of 34 male and 122 female consecutive patients who successfully underwent percutaneous balloon mitral valvuloplasty (PBMV). Clinical, echocardiographic, and hemodynamic variables were compared between male and female patients. Male patients were significantly older than female patients at the time of PBMV (39 years vs 34 years p < 0.05). Mitral valve score was significantly higher in male patients (p < 0.01). The mitral valve area before PBMV in male patients was significantly less than that in female patients (0.97 +/- 0.22 cm2 vs 1.09 +/- 0.25 cm2, respectively, p < 0.05). The pulmonary artery pressures of female patients before PBMV were higher than those of males (48 mm Hg vs 40 mm Hg, respectively, p < 0.05). The restenosis rates in male and female patients at the end of the follow-up period (38 months) were 20% and 9%, respectively (p < 0.05). In conclusion, male patients are older than female patients at the time of the PBMV procedure, and male patients have worse echocardiographic parameters and restenosis rates than female patients with the exception of pre-procedural pulmonary artery pressure. PMID- 11775626 TI - Suppression of fatty acid metabolism after exercise stress in patients with no electrocardiographic ST segment shift during balloon angioplasty. AB - Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomography (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12-lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning. PMID- 11775627 TI - Transcutaneous PO2 response to transient arterial occlusion in peripheral vascular disease detected by heating power oximeter. AB - Transcutaneous PO2 (TcpO2) was measured in 30 patients with peripheral arterial obstructive disease (PAOD) and in 30 age-matched controls in the hand and foot using a heating power electrode oximeter (HP-E). The HP-E was connected with a software modified monitor to simultaneously record changes in arterial stasis in the skin (TcpO2 mm Hg) and in the underlying tissue 3.5 to 4 mm from the HP-E (TcpO2 mW). In the hands of patients with PAOD, the following was found, lower mean values of the rest flow (R-F) and of the recovery area (Rc-Ar); delayed appearance of both a PO2 decrease after the start of stasis (ODT) and the increased value after the cuff deflation (ORT); and little relevance of flow changes in the tissues under the HP-E. In the foot homolateral to the obstructive lesion, the hemodynamic effects of the stasis were not consistently a result of circulatory insufficiency. In light-medium PAOD the correlation was more significant with the walking-free distance (WFD). However in severe PAOD, the perfusion was usually depressed and the variable values tended to flatten. This study confirmed the diagnostic reliability of this test in PAOD patients. Furthermore simultaneous exploration of two microvessel levels increased its diagnostic possibilities. PMID- 11775628 TI - Asymptomatic left ventricular permanent pacemaker malposition detected on routine follow-up--a case report. AB - The authors present an asymptomatic left ventricular pacemaker lead malposition that was detected upon routine 2-D Echocardiography. Clinical implication diagnosis and therapeutic options on left ventricular pacemaker lead malposition are discussed. PMID- 11775629 TI - Giant hiatal hernia presenting with stable angina pectoris and syncope--a case report. AB - A 70-year-old woman with giant hiatal hernia presented with stable angina pectoris and three syncope attacks in the previous 3 months. Chest radiography showed marked cardiomegaly and an air-fluid level at the basal region of the heart. A mixed type large hiatal hernia that distorted the heart was detected in contrast-enhanced computed tomography and esophagogastroduodenography. Postprandial nonsustained ventricular tachycardia was present on 24-hour Holter ECG monitoring. The patient's symptoms were attributed to giant hiatal hernia and improved following surgery. PMID- 11775630 TI - Plaque rupture on the carotid artery observed by Doppler ultrasonography--a case report. AB - Plaque rupture may play an important role in acute cerebral events. Recent technological advances in ultrasonographic systems provide a feasible diagnostic modality of atherosclerotic lesion by clearly visualizing flow conditions and vessel morphology. A 58-year-old man with chronic renal failure underwent duplex Doppler ultrasound in which ruptured plaque on carotid arterial wall was imaged. Color Doppler imaging showed that the plaque shoulder at the proximal site was hit by forward flow to the brain and ruptured. Curling flow in the inner space of the plaque was observed. Carotid arteriography at the corresponding site of ruptured plaque revealed the space within the plaque similarly contrasted. A magnetic resonance imaging of brain performed after identifying plaque rupture revealed small cerebral infarcts at the cerebral cortex. Plaque rupture could be demonstrated by color Doppler imaging at the proximal edge of plaque and curling flow in the intraplaque space may have released small thrombi to vessel lumen. Plaque rupture of the carotid artery may play an important role in the development of small cerebral infarction. PMID- 11775631 TI - Notifiable diseases annual summary. 1999. PMID- 11775632 TI - [95th French Congress on Urology. Paris, France, 14-17 November 2001. Abstracts]. PMID- 11775633 TI - Society for the Study of Fertility Annual Conference. University of Cambridge, July 2001. Abstracts. PMID- 11775634 TI - Evaluation of physical workload standards and guidelines from a Nordic perspective. PMID- 11775635 TI - [An attempt to combine humanitarianism and pacifism. The Red Cross and the Dutch movement for international peace]. AB - Both the International and the Dutch Red Cross were heavily damaged by World War II. The Red Cross movement especially was blamed for its lack of care for persecuted Jews and political prisoners. To restore its reputation all kinds of initiatives were taken. Amongst these was an attempt of the Dutch Red Cross to cooperate with several pacifist movements in the Dutch Movement for International Peace and Security. It seemed a good and sensible initiative, especially in 1945, but although it was supported by international Red Cross resolutions, it failed. The DRC grew immensely in numbers in the years after 1945. With the cold war coming up the peace movement lost most of its popularity and therefore lost its attraction for the Red Cross as a partner. As in the rest of its mutual history, the attempt to humanise war did not mix with the wish to abolish it. PMID- 11775636 TI - [Winkler's rabbits: the separation of the chairs in neurology and psychiatry in the Netherlands]. AB - In 1914/15 and in 1925/26 the selection of candidates for the professorships of psychiatry and neurology at the Universities of Amsterdam and Utrecht was fiercely debated. The central theme was the question whether either anatomy or clinical observation was the basic element of psychiatry. Eventually the choice for the latter of these two possibilities led to a separation of the two disciplines psychiatry and neurology. Paradoxically the stubbornness of the main defender of the anatomical standpoint, Cornelis Winkler, the professor in psychiatry and neurology who in 1914 went from Amsterdam to Utrecht where he retired in 1925, catalysed this divisionary process. PMID- 11775637 TI - [In memory of Dr. J. H. Sypkens Smit (1903-2001)]. PMID- 11775638 TI - [Evolution of phytochemical methods from XVIth to half-medium of XIXth century]. AB - In this study, the author shows that chemistry of natural plant products, and more generally of natural compounds, has known more difficulties in elaboration of suitable techniques soft and selective, for extraction, purification and analysis. It is at the end of the XVIIIth century and at the beginning of XIXth that first efficacious extraction methods were proposed and were codified, and consequently the chemistry of natural products was in continuous progress. PMID- 11775640 TI - Correction: Notice of Redundant Publication. PMID- 11775639 TI - [Auguste Laurent and alcaloids]. AB - A Laurent did not feel interested in alcaloids in the same way as his fellow chemists. He however investigated a great number of them, with much attention. These natural or artificial compounds constituted in his hands a medium to correct the results of many analyses, the size of molecules and to get a better knowledge of their structures. These nitrogenous substances make the joint of his chemical method, being together a hudge experimental field and a means to test his theory. PMID- 11775641 TI - Medicare program; changes to the hospital outpatient prospective payment system for calendar year 2002. Final rule. AB - This final rule revises the Medicare hospital outpatient prospective payment system to implement applicable statutory requirements, including relevant provisions of the Medicare, Medicaid,and SCHIP Benefits Improvement and Protection Act of 2000, and changes arising from our continuing experience with this system. In addition, it describes changes to the amounts and factors used to determine the payment rates for Medicare hospital outpatient services paid under the prospective payment system. This final rule also announces a uniform reduction of 68.9 percent to be applied to each of the transitional pass-through payments.These changes are applicable to services furnished on or after January 1, 2002. PMID- 11775642 TI - Essaven gel--review of experimental and clinical data. AB - Essaven gel (EG) has been developed for local treatment of venous and microcirculatory alterations (varicose veins, chronic venous insufficiency, associated signs and symptoms). Sport injuries (bruises, swelling secondary to sprains and contusions) respond favorably to EG, which is also indicated for varices in pregnancy. Active ingredients of EG are aescinate, sodium heparin, and essential phospholipids (EPL). The dose in 100 g of EG are: 1 g of aescinate, 10,000 IU of sodium heparin, and 1 g EPL. EG is applied several times daily in a thin film. Clinical reports on the activity of EG include several vascular applications in which the product is effective without contraindications or side effects. On the basis of this review, EG offers important therapeutic benefits to several types of patients and the product should be available for its usefulness and safety. PMID- 11775644 TI - Microangiopathy and venous ulceration: topical treatment with Essaven gel--a placebo-controlled, randomized study. AB - The involvement of the microcirculation in chronic venous insufficiency (CVI) due to venous hypertension causes venous hypertensive microangiopathy (VHM) and venous ulceration. VHM is characterized by the presence of enlarged convoluted capillaries; microvascular thrombosis with obliteration of some capillaries; increase in flux, permeability, and edema; and altered function of microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered, and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and an increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in 28 subjects with venous microangiopathy due to severe CVI and ulcers treated with a single acute application, Measurements of laser Doppler flux, PO2 and PCO2 in standardized conditions of application showed positive microcirculatory changes (significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). In conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single application. PMID- 11775643 TI - Microvascular changes in venous hypertension due to varicose veins after standardized application of Essaven gel--a placebo-controlled, randomized study. AB - The involvement of the microvascular structure in chronic venous insufficiency (CVI) causes venous hypertensive microangiopathy (VHM), which leads to venous ulceration. VHM is characterized by enlarged and ramified capillaries, increased flux and capillary permeability, edema, and altered function of microlymphatics. TcPO2 is decreased and CO2 increased. This perfusional paradox is caused by hyperperfusion in the deep skin layers with hypoperfusion of superficial nutritional capillaries. Exchanges in the capillary bed are altered. Nutritional skin alterations eventually lead to venous ulceration. Edema is the consequence of increased capillary pressure, reduced clearance, and by an increased exchange surface of capillaries. The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in 22 subjects with VHM due to severe varicose veins, treated with a single application. Measurements of flux, PO2 and PCO2 in standardized conditions of application indicated a significant decrease of the abnormally increased flux and CO2; PO2 increased in the treatment group. Essaven gel, in comparison with placebo and controls acutely improves the microcirculation in VHM even with a single application. PMID- 11775645 TI - Changes in microcirculation in venous ulcers with Essaven gel--a pilot, cross over, placebo-controlled, randomized study. AB - Microcirculatory changes in chronic venous insufficiency (CVI) due to venous hypertension produce venous hypertensive microangiopathy (VHM) and lead to ulceration. VHM is characterized by enlarged, convoluted capillaries; increase in flux, permeability, and edema; and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations in association with microtrauma may cause venous ulcers. The aim of this pilot, cross-over, randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) (single acute application) in 10 subjects with VHM and venous ulcers. The study was structured over 3 days: day 1 was used for the control evaluation for all patients. One group was randomized for the sequence placebo (day 2) and EG the following day; the second group with the sequence EG (day 2) and placebo (day 3). Independently from the sequence, measurements of flux and PO2 in standard conditions showed positive changes (significant decrease of the abnormally increased flux, PO2 increase) in the EG treatment group. Changes in the placebo group were limited and associated with skin manipulation. In conclusion, EG acutely improves microcirculation in limbs with VHM and ulceration even with a single application. PMID- 11775646 TI - Topical treatment of venous microangiopathy in patients with venous ulceration with Essaven gel--a placebo-controlled, randomized study. AB - The involvement of the microcirculation in chronic venous insufficiency (CVI), due to venous hypertension, causes venous hypertensive microangiopathy (VHM) and ulceration. VHM is characterized by enlarged, convoluted capillaries; microvascular thrombosis; obliteration of some capillaries; increase in flux, permeability, and edema and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate local treatment with Essaven gel (EG) in subjects with venous microangiopathy and ulcers. Measurements of laser Doppler flux, PO2, and PCO2 in standardized conditions showed positive changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). In conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single acute application. PMID- 11775647 TI - Microvascular alterations in diabetic microangiopathy: topical treatment with Essaven gel--a placebo-controlled, randomized study. AB - The involvement of the microcirculation in diabetic microangiopathy (DM) may be cause of severe invalidity and ulceration. Diabetic microangiopathy (DM) is characterized by a diffuse increase in skin flux, reduction in venoarteriolar response, and increased capillary permeability resulting in edema; skin PO2 is decreased and CO2 increased. In this condition, capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local foot care and treatment with Essaven gel (EG) in 30 subjects with DM and neuropathy and localized, small (<0.5 cm in maximum diameter) ulcers treated with a single acute application of EG. Measurements of laser Doppler (LDF) flux, PO2 and PCO2 in standardized conditions showed positive microcirculatory changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the active EG group lasting for at least 6 hours after application. Changes in the control group were not significant. In the placebo group variations were limited, mainly associated with skin manipulation and gel application. In conclusion, local treatment with one single standardized application of Essaven gel, in comparison with placebo, acutely improves the microcirculation in subjects with DM and small ulceration even with a single acute application. The microcirculatory changes are detectable even 10 hours after application. PMID- 11775648 TI - Two-week topical treatment with Essaven gel in patients with diabetic microangiopathy--a placebo-controlled, randomized study. AB - The involvement of the microcirculation in diabetic microangiopathy (DM) causes of severe incapacitation and ulceration. DM is characterized by a diffuse increase in flux, reduction in venoarteriolar response, associated with increased permeability resulting in edema and altered function of microlymphatics. In DM, skin PO2 is decreased and CO2 increased. In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local (foot) treatment with Essaven gel (EG) in 35 subjects with DM and neuropathy and localized, small (< 0.5 cm in maximum diameter) ulcers treated for 2 weeks. Measurements of laser Doppler (LDF) flux, PO2, and PCO2 in standardized conditions showed positive microcirculatory changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the active EG group. Changes in the control group were not significant. In the placebo group variations were limited (mainly associated with skin manipulation and gel application). In conclusion, local treatment for 2 weeks with standardized application of EG acutely improves the microcirculation in subjects with DM and small ulceration. PMID- 11775649 TI - Four-week treatment with Essaven gel in diabetic microangiopathy--a placebo controlled, randomized study. AB - The involvement of the microcirculation in diabetic microangiopathy (DM) may be the cause of severe incapacitation and ulceration. DM is characterized by a diffuse increase in skin flux, reduction in venoarteriolar response, and increased permeability, resulting in edema. In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local (foot) treatment with Essaven gel (EG) in 15 subjects with DM and neuropathy and treated with local application of EG for 4 weeks. Measurements of composite, average laser Doppler (LDF) flux (ten measurements points), in standardized conditions showed a significant decrease in flux in the EG group. The flux decrease was present even after 1 week after the suspension of treatment. Changes in the control group were not significant. In the placebo group, variations were limited (associated with skin manipulation and gel application). In conclusion local treatment for 4 weeks with standardized application of EG improves the microcirculation in subjects with DM. The changes are detectable even 1 week after the end of the treatment period. PMID- 11775650 TI - Microcirculation after standardized application of Essaven gel on normal skin--a placebo-controlled, randomized study. AB - Essaven gel (EG) is a naturally derived compound indicated for the treatment of impaired venous circulation and, in microcirculatory disorders, hematomas, swelling, sprains, and all minor sport injuries. The aim of this randomized, placebo-controlled, double-blind study was to evaluate the standardized application of EG on normal skin and its effects on the microcirculation. Standardization of gel application (particularly EG) has been recently described (in healthy subjects and in clinical studies) in defined steps. The results of this study indicate that topical treatment with EG is effective in improving or positively altering the microcirculation in normal skin both at the deeper capillary levels (thermoregulatory, whole-thickness capillary bed [as shown by laser Doppler flowmetry] as well as at the nutritional capillary layer (as shown by PO2). The application of EG can be standardized to obtain consistent results with topical treatment. PMID- 11775651 TI - Treatment of superficial vein thrombosis with standardized application of Essaven gel--a placebo-controlled, randomized study. AB - The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 4-week study evaluated the average skin temperature and an analogue symptomatic score. Below-knee SVT was associated with large varicose veins. In patients treated with active EG the decrease in score and in the average, composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage. In conclusion, treatment with EG in SVT improves symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective use of EG in SVT. PMID- 11775652 TI - Treatment of superficial vein thrombophlebitis of the arm with Essaven gel--a placebo-controlled, randomized study. AB - The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo and with a group of controls in 23 patients with superficial vein thrombophlebitis (SVTPH) of the arms. SVTPH was consequent to infusional treatment with an intravenous catheter. The 4-week study evaluated the average skin temperature and an analogue symptomatic score. In patients treated with active EG, the decrease in score and in composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage and to spontaneous resolution. In conclusion treatment with EG in arm SVTPH improves signs /symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective, local use of EG in SVTPH. PMID- 11775653 TI - Treatment of superficial vein thrombosis: clinical evaluation of Essaven gel--a placebo-controlled, 8-week, randomized study. AB - The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 8-week study evaluated SVT with an analogue clinical/symptomatic score. SVT was associated with varicose veins. In patients treated with active EG the decrease in score was significantly larger (p< 0.02) than in the placebo group. No intolerance was observed. The decrease in score in the placebo group was due to spontaneous resolution and to skin manipulation and massage. In conclusion local treatment with EG in SVT improves signs/symptoms much faster than placebo. This study confirms earlier observation on the effective, local use of EG in SVT. PMID- 11775654 TI - Acoustic relaxation spectrometers for liquids. AB - In this tutorial article methods of acoustic relaxation measurements of liquids are reviewed. The present performance of various techniques is described and desirable trends in future developments are shown. An account is given on standards in the optical monitoring of acoustic waves (Brillouin scattering), on time domain (jump) techniques, as well as on frequency domain (continuous and pulse modulated ultrasonic wave) methods. The merits and limitations of the different techniques of measurement, covering the frequency range from 10 kHz up to nearly 10 GHz now, corresponding with relaxation times between about 0.1 ms and 100 ps, are discussed. Efforts to further enhance the experimental accuracy and to reduce the required sample volume are indicated. PMID- 11775655 TI - Simultaneous measurement of sound velocity and wall thickness of a tube. AB - A method for simultaneously measuring the sound propagation velocity and the thickness of each wall on the opposite sides of a tube is presented. The method uses a pair of ultrasound transducers to produce two reflected pulses from the outer and inner surfaces of the tube wall on the each side, and two transmitted pulses, one with and one without the tube sample between the two transducers. Using the time-domain analysis, sound velocity and wall thickness of the tube are determined from the time delays between the three pairs of ultrasound pulses, whereas using the frequency-domain analysis, phase velocity, group velocity, and wall thickness of the tube are determined from the phase differences between the three pairs of ultrasound pulses. Results of measurements on five tube samples are reported. PMID- 11775656 TI - Stable reformulation of transfer matrix method for wave propagation in layered anisotropic media. AB - The numerical instability problem in the standard transfer matrix method has been resolved by introducing the layer stiffness matrix and using an efficient recursive algorithm to calculate the global stiffness matrix for an arbitrary anisotropic layered structure. For general anisotropy the computational algorithm is formulated in matrix form. In the plane of symmetry of an orthotropic layer the layer stiffness matrix is represented analytically. It is shown that the elements of the stiffness matrix are as simple as those of the transfer matrix and only six of them are independent. Reflection and transmission coefficients for layered media bounded by liquid or solid semi-spaces are formulated as functions of the total stiffness matrix elements. It has been demonstrated that this algorithm is unconditionally stable and more efficient than the standard transfer matrix method. The stiffness matrix formulation is convenient in satisfying boundary conditions for different layered media cases and in obtaining modal solutions. Based on this method characteristic equations for Lamb and surface waves in multilayered orthotropic media have been obtained. Due to the stability of the stiffness matrix method, the solutions of the characteristic equations are numerically stable and efficient. Numerical examples are given. PMID- 11775657 TI - Incident-angle dependence of the phase conjugate reflectivity by nonlinear piezoelectric interaction in PZT ceramics. AB - The reflectivity of an acoustic phase conjugator by nonlinear piezoelectric interaction in PZT ceramics was measured as a function of the incident angle. The phase conjugator was designed as a solid block with a flat surface for the acoustic incidence from water. The phase conjugate reflectivity showed incident angle dependence, which is mainly determined by the transmissivity of the acoustic waves, together with some effects of anisotropy. The field reconstructing ability of this phase conjugator was simulated for focused incident beams. PMID- 11775658 TI - Diffusion of ultrasound in concrete. AB - The propagation and scattering of ultrasound in concrete is discussed. The heterogeneous composition of concrete causes the ultrasound to scatter considerably. In the limit of many scattering events, the ultrasonic energy density in circular cylinders of concrete is shown to evolve in accordance with a one-dimensional diffusion equation. The ultrasonic diffusivity and dissipation are measured experimentally over the frequency range of 100-900 kHz. Theoretical descriptions of the diffusivity are in accord with the experimental values. Such frequencies are well above typical frequencies used for concrete inspection. Thus, it is anticipated that the use of these higher frequencies will result in new techniques for characterizing material properties and damage in concrete structures. PMID- 11775659 TI - Generation of ultraharmonics in surfactant based ultrasound contrast agents: use and advantages. AB - A unique distinction between surfactant stabilized ultrasound contrast agent ST68 and water (or tissue), is the enhanced ability of the agent to generate non linear frequencies such as sub-harmonics (f0/2), higher harmonics (2fo, 3fo, 4fo,...), and ultraharmonics (3f0/2, Sf0/2, 7f0/2,...), when insonated with fundamental frequency f0. Currently, second harmonics (2f0) have been predominantly researched, to exploit the diagnostic benefits of the contrast specific non-linear imaging. However, we found that at normal imaging pressures (100 kPa-1 MPa), ST68 agent-generated second harmonic enhancements dropped to approximately 8 dB at 100 kPa and approximately 2 dB at 1 MPa. Moreover, at these pressures water (or tissue) produced strong second harmonics due to non-linear propagation. Ultraharmonics and sub-harmonics on the other hand, were generated only by the agent, and were not produced due to the non-linear propagation of ultrasound in either water or tissue. Additionally, ultraharmonic (3f0/2) enhancements of approximately 23 dB at 100 kPa, approximately 35 dB at 0.5 MPa and approximately 41dB at 1.1 MPa for ST68-PFC, offer much greater signal to noise ratio than higher harmonics. PMID- 11775660 TI - High accuracy non-contact ultrasonic thickness gauging of aluminium sheet using electromagnetic acoustic transducers. AB - Aluminium sheet thickness has been calculated from ultrasonic data obtained using a send-receive, radially polarised electromagnetic acoustic transducer (EMAT). Sheets in the thickness range between 0.1 and 0.5 mm have been measured using this non-contact approach at a stand-off of up to 1.5 mm. Normal incidence shear waves generated and detected in the sheet and the resultant waveforms have been processed using transit time measurements and Fourier analysis. Two broad band EMAT systems have been used to perform the measurements with centre frequencies of approximately 5 MHz and frequency content up to 10 and 20 MHz respectively. The most accurate measurements of thickness on thin sheets have been made using Fourier analysis and have yielded measurements accurate to within 0.2% (or 0.4 microm) for 280 microm thick aluminium sheets. Discrete shear wave echoes can be observed for sheets down to a thickness of 250 microm using the higher frequency EMAT system. However temporal measurements of these signals yield lower accuracy results when compared to the Fourier analysis method which is capable of sub micron accuracy. PMID- 11775661 TI - Bernoulli excitation and detection of gas bubbles. AB - A simple method is proposed for detecting and sizing bubbles in pipeline fluid flow. This is based on changing the pressure of the fluid, which in turn excites volume oscillations in the bubble. If the change in pressure is of sufficient brevity and magnitude, the transient distortion results in excitation of the bubble into radiative oscillation at its natural frequency. In a moving fluid, the Bernoulli equation predicts that such a pressure change can be achieved through a suitable gradient in the flow velocity. In the experiments described here, this is achieved by altering the cross-sectional area of the pipe in which the fluid is flowing. We demonstrate the efficacy of this excitation method and, by detecting the radiated sound using a nearby hydrophone, determine the size of individual bubbles from their characteristic oscillation frequency. PMID- 11775662 TI - PIV applied to eckart streaming produced by a medical ultrasound transducer. AB - Particle image velocimetry (PIV) is applied for the first time to study Eckart streaming induced by a medical ultrasonic transducer operating at a frequency of 3.3 MHz and effective acoustic intensities of 0.25 and 3 Wcm(-2). A temporal series of velocities in a two-dimensional plane were recorded resulting in an experimental set comprising over half a million velocity data points. These enabled average and fluctuating properties to be determined and clearly indicated the quasi-steady nature of the flow. The average large scale velocity fluctuations along the axis caused by this quasi-steady property were calculated to be 2 and 20 m ms(-1) at effective intensities of 0.25 and 3 Wcm(-2) respectively corresponding to approximately 25% of the peak flow velocity in both cases. Furthermore averaged shear rates were calculated with peak values of 1 and 8 s(-1) for the low and high intensities respectively. The present investigation indicates the usefulness of PIV for such studies and serves as a prelude to investigations of streaming in biological type fluids. PMID- 11775663 TI - Quartz strip resonators as a temperature sensor. AB - The miniature frequency-temperature sensor in the form of a small quartz strip vibrating in the thickness-shear mode with the resonant frequency in the range from 4 to 8 MHz is considered. Y-cut strips rotated in the range from 0 degrees to 27 degrees are the subject of the study. The temperature coefficients of the resonance frequency for the different rotation angles are given. The different temperature dependence of the resonant frequency of the quartz temperature sensors vibrating on the fundamental and harmonic frequency of the thickness shear modes is pointed out. PMID- 11775664 TI - Closing gaps in mental health care for persons with serious mental illness. PMID- 11775665 TI - HMO penetration, competition, and risk-adjusted hospital mortality. AB - OBJECTIVE: HMOs have been shown to have an effect on the care provided directly to their enrollees. They may also influence the care provided to individuals in fee-for-service plans through a spill-over effect. The objective of this study was to investigate the associations among HMO market penetration, HMO and hospital competition, and the quality of care received by Medicare fee-for service patients measured by risk-adjusted hospital mortality rates. DATA SOURCES: The 1990 data for 1,927 hospitals in 134 metropolitan statistical areas (with five or more hospitals) included Medicare fee-for-service risk-adjusted mortality rates from the Medicare Hospital Information Reports, hospital characteristics from the American Hospital Association annual survey, and HMO market penetration and competition calculated from InterStudy and Group Health Association of America data. STUDY DESIGN: Statistical regression techniques were used to identify the associations between HMO market penetration, competition, and risk-adjusted mortality, controlling for other hospital characteristics and region. PRINCIPAL FINDINGS: Higher HMO market penetration and to a lesser degree increased HMO competition were associated with better mortality outcomes for fee for-service Medicare enrollees. Competition between hospitals did not exhibit a significant association. CONCLUSIONS: HMOs may have a spill-over effect on quality of care received by individuals enrolled in fee-for-service plans. These findings may be explained by a positive effect on local practice styles or a preferential selection by HMOs for areas with better hospital care. PMID- 11775666 TI - Medical care expenditures under gatekeeper and point-of-service arrangements. AB - OBJECTIVE: To compare expenditures for medical care in a closed-panel gatekeeper HMO and an open-panel point-of-service (POS) plan that share the same provider network. DATA SOURCE/STUDY SETTING: The two study HMOs are distinct product lines of a single managed care organization; both plans are commercial products. We used administrative data files from the study plans for 1994-95 to assess differences in total medical care expenditures and spending for five categories of services: physician services, inpatient hospital services, outpatient hospital services, prescription drugs, and other services. STUDY DESIGN: Multivariate analyses were based on the two-part model of the demand for medical care. The dependent variables in these models were expenditures in each of the five categories of services, and the independent variables were indicator variables for plan type and visit copayments, prescription drug copayment, distance to the nearest primary care physician (PCP), demographic characteristics, chronic conditions, area characteristics, and entry/exit indicator variables. PRINCIPAL FINDINGS: Total expenditures for medical care ranged from equal in both plans to 7 percent higher in the gatekeeper HMO (p < .10), depending on the copayments for physician visits. Expenditures were not higher in the POS plan for any of the five categories of services. These findings were robust to a wide range of sensitivity analyses. CONCLUSIONS: Direct patient access to specialists in POS plans does not necessarily result in higher medical care expenditures. When POS enrollees are required to choose PCPs, patient cost sharing, physician financial incentives, and utilization review may control expenditures without constraining direct patient access to providers. PMID- 11775667 TI - Do patient assessments of primary care differ by patient ethnicity? AB - OBJECTIVE: To determine if patient assessments (reports and ratings) of primary care differ by patient ethnicity. DATA SOURCES/STUDY DESIGN: A self-administered patient survey of 6,092 Massachusetts employees measured seven defining characteristics of primary care: (1) access (financial, organizational); (2) continuity (longitudinal, visit based); (3) comprehensiveness (knowledge of patient, preventive counseling); (4) integration; (5) clinical interaction (communication, thoroughness of physical examinations); (6) interpersonal treatment; and (7) trust. The study employed a cross-sectional observational design. PRINCIPAL FINDINGS: Asians had the lowest primary care performance assessments of any ethnic group after adjustment for socioeconomic and other factors. For example, compared to whites, Asians had lower scores for communication (69 vs. 79, p = .001) and comprehensive knowledge of patient (56 vs. 48, p = .002), African Americans and Latinos had less access to care, and African Americans had less longitudinal continuity than whites. CONCLUSIONS: We do not know what accounts for the observed differences in patient assessments of primary care. The fact that patient reports as well as the more subjective ratings of care differed by ethnicity suggests that quality differences might exist that need to be addressed. PMID- 11775668 TI - Pennsylvania's early discharge legislation: effect on maternity and infant lengths of stay and hospital charges in Philadelphia. AB - OBJECTIVE: To assess the effect of maternal length of stay (LOS) legislation on LOS and hospital charges associated with Philadelphia resident live births from 1994 through 1997. DATA SOURCE/STUDY SETTING: This was a descriptive epidemiological study involving secondary data analyses of linked birth record and hospital discharge data pertaining to all Philadelphia resident live births occurring between January 1, 1994 and December 31, 1997. STUDY DESIGN: Using these linked data, trends in median and mean maternal and infant LOS and hospital charges were described for three distinct time periods: (1) a "prelegislative" period (January 1, 1994 through June 30, 1995); (2) a one-year period during which LOS legislation was introduced, debated, modified, and eventually passed by Pennsylvania lawmakers (July 1, 1995 through June 30, 1996); and (3) a "post-LOS law" period immediately following enactment of Act 85 mandating minimum LOS for mothers and their newborns (July 1, 1996 through December 31, 1997). LOS variables for both mothers and infants were calculated based on the actual number of hours elapsing between birth and discharge; hospital charges were obtained directly from information available in the Hospital Discharge Survey data. PRINCIPAL FINDINGS: Maternal median charges and LOS per delivery for vaginal births rose from 5,270 dollars to 6,333 dollars and from 35 to 47 hours following the enactment of Pennsylvania maternal minimum LOS legislation. Median infant cost and LOS per delivery mirrored these trends. CONCLUSIONS: Pennsylvania LOS legislation had a profound effect on maternal and infant discharge practices in Philadelphia. As much as $20 million may have been added to annual health care costs associated with Philadelphia resident births. PMID- 11775669 TI - Constructs of burden of illness in older patients with breast cancer: a comparison of measurement methods. AB - OBJECTIVE: The burden of illness can influence treatment decisions, but there are limited data comparing the performance of different illness burden measures. We assessed the correlations between five previously validated measures of illness burden and global health and physical function and evaluated how each measure correlates with breast cancer treatment patterns in older women. DATA SOURCE: A cohort of 718 women > 67 years with early-stage breast cancer formed the study group. STUDY DESIGN/DATA COLLECTION METHODS: The study made a cross-sectional comparison of illness burden measures (Charlson index, Index of Co-existent Diseases, cardiopulmonary burden of illness, patient-specific life expectancy, and disease counts) and physical function and self-rated global health status. Data were collected from records and patient interviews. PRINCIPAL FINDINGS: All of the measures were significantly correlated with each other and with physical function and self-rated health (p < .001). After controlling for age and stage, life expectancy had the largest effect on surgical treatment, followed by self rated physical function and health; life expectancy was also independent of physical function. For instance, women with higher life expectancy and better self-rated physical function and health were more likely to receive breast conservation and radiation than sicker women. Women with higher physical functioning were more likely to receive adjuvant chemotherapy than women with lower functioning. CONCLUSIONS: Several measures of illness burden were associated with breast cancer therapy, but each measure accounted for only a small amount of variance in treatment patterns. Future work is needed to develop and validate measures of burden of illness that are feasible, comprehensive, and relevant for diverse clinical and health services objectives. PMID- 11775670 TI - A global measure of physical functioning: psychometric properties. AB - OBJECTIVE: To examine the psychometric properties of a global physical functioning scale (GPFS) developed as a self-report measure and constructed to scale physical functioning from very poor (1) to excellent (100). DATA SOURCES: Data collection took place between January 1997 and September 1999. It consisted of self-ratings of surgical patients and the ratings of clinicians. The setting was the surgical department at a university hospital. STUDY DESIGN: Test-retest reliability and the convergence of the scores of patients and clinicians were examined in 106 patients before elective coronary or gastrointestinal surgery. Inter-rater reliability was tested in 36 hospitalized patients with cardiologic or vascular surgical diseases who were rated by random selection from a pool of 91 clinicians. The patients also rated their physical functioning. Discriminative validity, sensitivity to change, ceiling and floor effects, and influence of emotional state upon the scores were tested in 127 patients in six diagnostic groups who scored the GPFS before and subsequent to surgery. The concurrent validity was examined in 101 patients who scored the GPFS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) before elective coronary surgery. PRINCIPAL FINDINGS: The test-retest correlation (.90), correlation of the scores of the clinicians and patients (.87), and rater intraclass correlation coefficient (.82) were high. The GPFS discriminated among patients with different levels of physical functioning, and it was sensitive to change following coronary surgery. There were moderate ceiling and no floor effects. The correlation with the physical functioning scale of the SF-36 (PF-10) was .67. The GPFS differentiated patients with middle levels of physical functioning better than did the PF-10. CONCLUSIONS: The psychometric properties of the GPFS appeared adequate as a measure of general physical functioning. The scale is easy to use and also appears suitable for outcome studies following substantial changes in physical functioning as after coronary surgery. PMID- 11775671 TI - Racial and ethnic disparities and primary care experience. PMID- 11775673 TI - Selective radical reactions in multiphase systems: phase-transfer halogenations of alkanes. AB - The present paper shows that selective radical reactions can be initiated and carried out in multiphase systems. This concept is applied to the selective functionalization of unactivated aliphatic hydrocarbons, which may be linear, branched, and (poly)cyclic, strained as well as unstrained. The phase-transfer system avoids overfunctionalization of the products and simplifies the workup; the selectivities are excellent and the yields are good. This is the only method for direct preparative iodination of alkanes applicable to large scale as well. We demonstrate that the reaction systems are indeed phase-transfer catalyzed through a systematic study of variations of the reactants, solvents, catalysts, and by measuring as well as computing the H/D kinetic isotope effects for the rate-limiting C-H abstraction step by *CHal3 radicals which are held responsible for the observed radical reactions. In the case of *CBr3, this key intermediate could also be trapped under otherwise very similar reaction conditions. To stimulate further work, the tolerance of some functional groups was tested as well. PMID- 11775674 TI - Non-sequential processes for the transformation of a racemate into a single stereoisomeric product: proposal for stereochemical classification. AB - Non-sequential processes which allow the transformation of a racemate into a single stereoisomeric product without the occurrence of an "undesired" isomer are classified according to their underlying stereochemistry. A re-definition of the term "de-racemization" is proposed. PMID- 11775672 TI - The prevalence and correlates of untreated serious mental illness. AB - OBJECTIVE: To identify the number of people in the United States with untreated serious mental illness (SMI) and the reasons for their lack of treatment. DATA SOURCE/STUDY DESIGN: The National Comorbidity Survey; cross-sectional, nationally representative household survey. DATA COLLECTION: An operationalization of the SMI definition set forth in the Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act identified individuals with SMI in the 12 months prior to the interview. The presence of SMI then was related to the use of mental health services in the past 12 months. PRINCIPAL FINDINGS: Of the 6.2 percent of respondents who had SMI in the year prior to interview, fewer than 40 percent received stable treatment. Young adults and those living in nonrural areas were more likely to have unmet needs for treatment. The majority of those who received no treatment felt that they did not have an emotional problem requiring treatment. Among those who did recognize this need, 52 percent reported situational barriers, 46 percent reported financial barriers, and 45 percent reported perceived lack of effectiveness as reasons for not seeking treatment. The most commonly reported reason both for failing to seek treatment (72 percent) and for treatment dropout (58 percent) was wanting to solve the problem on their own. CONCLUSIONS: Although changes in the financing of services are important, they are unlikely by themselves to eradicate unmet need for treatment of SMI. Efforts to increase both self-recognition of need for treatment and the patient centeredness of care also are needed. PMID- 11775675 TI - Structural characterization and intramolecular aliphatic C-H oxidation ability of M(III)(mu-O)2M(III) complexes of Ni and Co with the hydrotris-(3,5-dialkyl-4-X pyrazolyl)borate ligands TpMe2,X (X = Me, H, Br) and TpiPr2. AB - Reaction of the dinuclear M(II)-bis(mu-hydroxo) complexes of nickel and cobalt, [(M(II)(TpR)]2(mu-OH)2] (M = Ni; 3Ni M = Co: 3Co), with one equivalent of H2O2 yields the corresponding M(III)-bis(mu-oxo) complexes, [[M(III)(TpR)]2-(mu-O)2] (M=Ni; 2Ni, M=Co: 2Co). The employment of a series of TpMe2,X (TpMe2,X = hydrotris(3,5-dimethyl-4-X-1-pyrazolyl)borate; X = Me, H, Br) as a metal supporting ligand makes it possible to isolate and structurally characterize the thermally unstable M(III)-bis-(mu-oxo) complexes 2Ni and 2Co. Both the starting (3Ni and 3Co) and resulting complexes (2Ni and 2Co) contain five-coordinate metal centers with a slightly distorted square-pyramidal geometry. Characteristic features of the nickel complexes 2Ni, such as the two intense absorptions around 400 and 300 nm in the UV-visible spectra and the apparent diamagnetism, are very similar to those of the previously reported bis(mu-oxo) species of Cu(III) and Ni(III) with ligands other than TpR, whereas the spectroscopic properties of the cobalt complexes 2Co (i.e., paramagnetically shifted NMR signals and a single intense absorption appearing at 350 nm) are clearly distinct from those of the isostructural nickel compounds 2Ni. Thermal decomposition of 2Ni and 2Co results in oxidation of the inner saturated hydrocarbyl substituents of the TpR ligand. Large kH/kD values obtained from the first-order decomposition rates of the TpMe3 and Tp(CD3)2,Me derivatives of 2 evidently indicate that the rate-determining step is an hydrogen abstraction from the primary C-H bond of the methyl substituents. mediated by the M(III)2-(mu-O)2 species. The nickel complex 2Ni shows reactivity about 10(3) times greater than that of the cobalt analogue 2Co. The oxidation ability of the M(III)(mu-O)2M(III) core should be affected by the hindered TpR ligand system, which can stabilize the +2 oxidation state of the metal centers. PMID- 11775676 TI - Conducting-polymer electrochemical switching as an easy means for control of the molecular properties of grafted transition metal complexes. AB - Copper(II) 3',4'-bis(N,N'-oxamato)terthiophene has been synthesized and electropolymerized. The copper(II)-complex centers are not affected by the polymerization process, which involves coupling between Calpha carbon atoms of the terthiophene units and leads to a new conjugated polymer consisting of polythiophene chains bearing bis(oxamato)-Cu(II) groups regioregularly grafted onto the polymer backbone. The polymer is stable with respect to polythiophene electroactivity, and no demetallation or modification of the Cu oxidation state occurs over a large potential range. In this material, the two moieties exhibit direct electronic interaction, which makes it possible to use the conductive polymer backbone as a molecular wire or a nanocontact capable of inputting to the bis(oxamato)-Cu(II) groups through the polythiophene-switching reaction. FTIR, XPS, and XAS spectroscopies have been used to study the effect of the state of the conducting polymer upon the properties of the copper(II) center (electron density, ligand field strength, size of cavity, force constants of some bonds). These properties can be controlled to some extent by the potential applied to this device. From the point of view of the copper(II) center, this effect is similar to the grafting of substituents with various electronic properties. PMID- 11775677 TI - Host-guest interaction of 12-MC-4, 15-MC-5, and fused 12-MC-4 metallacrowns with mononuclear and binuclear carboxylato complexes: structure and magnetic behavior. AB - Interaction of manganese with salicylhydroxamic ligands leads to the formation of the 12-membered metallacrown [Mn(II)(2(2,4-DP)2(HCOO)2]-[12-MC(Mn(III)N(shi) 4](py)6 (2) (H-2,4-DP =2-(2,4-dichlorophenoxy)propionic acid) and the 15-membered metallacrown [Mn(II)(2,4-D)2][15-MC(Mn(III)N(shi)-5](py)6 (1) (H-2,4-D = 2,4 dichlorophenoxyacetic acid). The crystal structure analysis shows that mononuclear and dinuclear alkanoato complexes are accommodated in the cavity of the metallacrown ring. The magnetic behaviour of 1 and 2 and the magnetic behaviour of the fused 12-membered metallacrown [Ni(II)(mcpa)]2-[12 MC(Ni(II)N(shi)2(pko)2-4][12-MC(Ni(II)N(shi)3(pko)-4]-(CH3OH)3(H2O) (3) (Hmcpa = 2-methyl-4-chlorophenoxyacetic acid) have shown that the zero field and/or the population of many energy levels at low temperatures is the reason for the divergence of the susceptibility data at high fields. For compound 3, the ground state is S = 0, with S = 1 and S = 2 low-lying excited states. This leads to a non-Brillouin behaviour of the magnetisation, since the ground state is very close to the excited states. PMID- 11775678 TI - Studies on the mechanism of metal-catalyzed hydrogen transfer from alcohols to ketones. AB - The mechanism of metal-catalyzed hydrogen transfer from alcohols to ketones has been studied. Hydrogen transfer (H-transfer) from (S)-alpha-deutero-alpha phenylethanol ((S)-1) to acetophenone was used as a probe to distinguish between selective carbon-to-carbon H-transfer and nonselective transfer involving both oxygen-to-carbon and carbon-to-carbon H-transfer. The progress of the reaction was monitored by the decreasing enantiomeric excess of (S)-1. After complete racemization, the alcohol was analyzed for its deuterium content in the alpha position, which is a measure of the degree of selectivity in the H-transfer. A number of different rhodium, iridium, and ruthenium complexes (in total 21 complexes) were investigated by using this probe. For all rhodium complexes a high degree of retention of deuterium at alpha-carbon (95-98%) was observed. Also most iridium complexes showed a high degree of retention of deuterium. However, the results for the ruthenium complexes show that there are two types of catalysts: one that gives a high degree of deuterium retention at alpha-carbon and another that gives about half of the deuterium content at alpha-carbon (37 40%). Two different mechanisms are proposed for transition-metal-catalyzed hydrogen transfer, one via a monohydride (giving a high D content) and another via a dihydride (giving about half of D content). As comparison non-transition metal-catalyzed hydrogen transfer was studied with the same probe. Aluminum- and samarium-catalyzed racemization of (S)-1 gave 75-80% retention of deuterium in the alpha-position of the alcohol, and involvement of an electron transfer pathway was suggested to account for the loss of deuterium. PMID- 11775679 TI - Synthesis, structure, spectroscopic properties, and electrochemistry of rare earth sandwich compounds with mixed 2,3-naphthalocyaninato and octaethylporphyrinato ligands. AB - A series of 14 heteroleptic rare earth sandwich complexes [M(III)-(nc)(oep)] (M=Y, La-Lu except Ce and Pm; nc=2,3-naphthalocyaninate; oep = octaethylporphyrinate) have been prepared by a one-pot procedure from corresponding [M(acac)3] . nH2O (acac = acetylacetonate), metal-free porphyrin H2(oep), and naphthalonitrile the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in n-octanol. The molecular structures of four of these complexes (M = Sm, Gd, Y, Lu) are isostructural, exhibiting a slightly distorted square antiprismatic geometry with two domed ligands. The interplanar distance decreases from 2.823 to 2.646 A along the series as a result of lanthanide contraction. The whole series of complexes have also been characterized spectroscopically. All the electronic absorptions, except the two B-bands due to nc and the oep rings, are metal-dependent, indicating that there are substantial pi-pi interactions. The hole or the unpaired electron in these double-deckers is delocalized over both macrocyclic ligands, as evidenced by the co-appearance of the IR marker bands for the nc*- (1315-1325 cm(-1)) and oep*- (1510-1531 cm(-1)) T radical ions. Three one-electron oxidation couples and up to three one-electron reduction couples have been revealed by electrochemical methods. All the potentials are linearly dependent on the size of the metal center. The changes in absorption spectra during the first electro-oxidation and reduction of the La(III), Eu(III), and Y(III) double-deckers have also been studied spectroelectrochemically. The spectral data recorded for [M(III)(nc)(oep)]-(M = Y, La-Lu except Ce and Pm) reduced chemically with hydrazine hydrate are in accord with those obtained by spectroelectrochemical methods. The first heteroleptic naphthalocyaninate containing triple-deckers [M(III)2(nc)-(oep)2] (M = Nd, Eu) have also been prepared by a raise-by-one-story method by using [M(III)(nc)(oep)] (M = Nd, Eu), [M(acac)3] . nH2O (M = Nd, Eu), and H2(oep) as starting materials. The compounds adopt a symmetrical triple-decker structure with two outer oep rings and one inner nc ring, which has been confirmed by 'H NMR spectroscopy and X-ray structural determination of the Nd complex. Both compounds give a near-IR absorption at 1021 nm (for M=Nd) or 1101 nm (for M = Eu), which has rarely been observed for neutral (or hole-free) triple-decker complexes and can be ascribed to the lowest-energy Q'(0, 0) transition. Similarly to the double-decker analogues. these triple-decker complexes undergo a series of one-electron transfer processes with a relatively small potential gap (1.1 -1.2 V) between the first oxidation and the first reduction. PMID- 11775681 TI - Highly selective formation of [4+2] and [4+3] cycloadducts of tetrahydroindenes generated in situ from a (1-alkynyl)carbene tungsten complex by the metalla-1,3,5 hexatriene route. AB - 1-Amino-3-ethoxytetrahydro-3aH-indenes 8 can be readily generated together with pentacarbonyl(pyridine)tungsten in a template induced three-component reaction of [(1-cyclohexenyl)ethynyl]carbene tungsten complex 1 with secondary amines 2a-d and pyridine. Even though the compounds 8 are thermally quite unstable and undergo a fast rearrangement to tetrahydro-7aH-indenes 7. they can be trapped by formation of (rather strained) [4+2] cycloadducts 12 with maleimide 11. If 1 amino-3-ethoxytetrahydro-3aH-indenes 8 are generated in the presence of electron poor alkynes 2a and 2b, they undergo a 1,5-shift to give tetrahydro-7aH-indenes 7, which in turn afford [4+2] cycloadducts 4a-d. Condensation of 1-tungsta-1,3,5 hexatrienes (3E)-5a-d with 1-metalla-1,3-butadienes 14 (M = Cr, W) give [4+3] cycloadducts 15a-e of tetrahydro-7aH-indenes 7 in good yields with high regio- and stereoselectivity. PMID- 11775680 TI - S-position isomers of BEDT-TTF and EDT-TTF: synthesis and influence of outer sulfur atoms on the electrochemical properties and crystallographic network of related organic metals. AB - The synthesis and characterization of new modified tetrathiafulvalenes (TTF), the S-position isomers of BEDT-TTF and EDT-TTF, are described. The synthetic strategy presented in this work is based on an efficient and unprecedented two-step sequence for the conversion of a vicinal bis(hydroxymethyl) functionality into a disulfide ring. Different routes are discussed in terms of efficiency for the synthesis of the symmetric S-position isomer of BEDT-TTF and that of EDT-TTF. Their electrochemical properties are combined with data obtained from UV/Vis spectroscopy and orbital calculations, and the electronic influence of peripheral sulfur atoms on the neutral and oxidized species is discussed. The introduction of these outer sulfur atoms at the periphery of the TTF core gives rise to specific intermolecular S...S interactions in the corresponding organic materials. Crystallographic studies of radical cation salts synthesized upon electrocrystallization clearly showed that the network obtained is dictated by the outer sulfur atoms, which are responsible for a characteristic and unprecedented "windmill" array. PMID- 11775682 TI - Selective encapsulation of chloride ions within novel cage host complexes in the presence of equimolar amounts of chloride and bromide ions. AB - Four macrotricyclic cage hosts which feature four positive binding sites oriented toward the center of the intramolecular cavity are presented as promising candidates for anion receptors and they have been expected to play a important role in the selective encapsulation of the halide ion Cl- or Br . The complementarity between a macrotricyclic quaternary ammonium ion and Cl- was achieved by fine-tuning of the four ammonium nitrogen atoms and the endocyclic methylene groups. The cage hosts [R4N4(C5H10)4(C6H12)2]4+ (abbreviated as [556]) showed perfect encapsulation of all chloride ions in acetonitrile at 0 < r= ([Cl ]o/[[556]]o) < or = 1 within the sensitivity of the 1H NMR spectra in combination with a rather slow chemical exchange of the Cl- ion in an encapsulation/decapsulation equilibrium with [556]. Further, the selective encapsulation of all the chloride ions into [556] cage occurs unambiguously at r = 1 in the presence of equimolar amounts of Br-. The structural complementarity of the newly designed [556] host prevails over the Hofmeister-series restraints determined by differences in Gibbs free energy of halide anion solvation. PMID- 11775683 TI - Figure-eight tetrathiaoctaphyrin and dihydrotetrathiaoctaphyrin. AB - The acid-catalyzed condensation of pyrrole and 2,5-bis(p tolylhydroxymethyl)thiophene yields two novel giant heteroporphyrins: 5,10,15,20,25,30, 35,40-octa(p-tolyl)-41,43,45,47 tetrathia[36]octaphyrin(1.1.1.1.1.1.1.1) (S4OP) and 5,10,15,20,25,30,35,40-octa(p tolyl)-dihydro-41,43,45,47-tetrathia[38]octaphyrin(1.1.1.1.1.1.1.1) (S4OPH2). These tetrathiaoctaphyrins are interconvertible through dihydrogenation or dehydrogenation processes. Both compounds possess helical figure-eight geometry with two thiophene rings for S4OP or two pyrrole rings for S4OPH2 in the ribbon crossing center as shown by NOESY experiments. The synthesis of the figure-eight tetrathiaoctaphyrin implies a prearrangement process to form helical M or P dithiatetrapyrromethanes. The P-P or M-M condensation leads to the figure-eight molecule in competition with an intramolecular ring closure. Two dithiaporphyrin like pockets of S4OP or S4OPH2 behave as independent proton acceptors. The stepwise process yields symmetric or asymmetric cationic species that depends on whether an even or odd number of NH protons are added. Dihydrotetrathiaoctaphyrin contains 38 pi electrons in its conjugation pathway, which corresponds to the formal [4n + 2] Huckel type pi-electron formulation that is consistent with a modest diatropic ring current effect in their 1H NMR spectra. The formal 4n type pi-electron formulation for tetrathiaoctaphyrin accounts for the residual paratropic shifts. A figure-eight conveyor-belt-like movement of the whole macrocyclic ring without a racemization step is proposed to account for the dynamic properties of S4OP. The molecule shuttles between two degenerate configurations. A S4OP-S4OPH2 couple may be considered as a molecular element which, while preserving the overall figure-eight geometry, "chooses" pyrrole or thiophene rings as spacers as a function of the macrocyclic oxidation state. PMID- 11775684 TI - Tetraphenylbenziporphyrin--a ligand for organometallic chemistry. AB - 6,11,16,21-Tetraphenylbenziporphyrin (TPBPH)H, an analogue of tetraphenylporphyrin with one of the pyrrole groups replaced by a benzene ring, is formed in good yield in the condensation of the appropriate precursor with pyrrole and benzaldehyde. (TPBPH)H gives organometallic complexes with palladium(II) and platinum(II), [(TPBP)PdII] and [(TPBP)PtII], in which the metal ion is bound in the macrocyclic cavity by three pyrrolic nitrogen atoms and a carbon atom of the benzene ring. In the reaction with silver(I) acetate benziporphyrin does not yield a stable complex but undergoes selective acetoxylation at the internal carbon atom. (TPBPH)H is reversibly reduced to 6 benziphlorin and reacts with a water or methanol molecule to give 6-hydroxy- or 6 methoxy-6-benziphlorin, respectively. PMID- 11775685 TI - Synthesis and preliminary testing of molecular wires and devices. AB - Presented here are several convergent synthetic routes to conjugated oligo(phenylene ethynylene)s. Some of these oligomers are free of functional groups, while others possess donor groups, acceptor groups, porphyrin interiors, and other heterocyclic interiors for various potential transmission and digital device applications. The syntheses of oligo(phenylene ethynylene)s with a variety of end groups for attachment to numerous metal probes and surfaces are presented. Some of the functionalized molecular systems showed linear, wire-like, current versus voltage (I(V)) responses, while others exhibited nonlinear I(V) curves for negative differential resistance (NDR) and molecular random access memory effects. Finally, the syntheses of functionalized oligomers are described that can form self-assembled monolayers on metallic electrodes that reduce the Schottky barriers. Information from the Schottky barrier studies can provide useful insight into molecular alligator clip optimizations for molecular electronics. PMID- 11775686 TI - The reactivity of N-coordinated amides in metallopeptide frameworks: molecular events in metal-induced pathogenic pathways? AB - The amino acid derived tertiary amide ligand tert-butoxycarbonyl-(S)-alanine-N,N bis(picolyl)amide (Boc-(S)-Ala-bpa, 1) has been synthesized as a model for metal coordinating peptide frameworks. Its reactions with copper(II) and cadmium(II) salts have been studied. Binding of Cu2+ results in amide bond cleavage and formation of [(bpa)(solvent)Cu]2+ complexes. In contrast, the stable, eight coordinate complex [(Boc-(S)-Ala-bpa)Cd(NO3)2] (5) has been isolated and characterized by X-ray crystallography. An unusual tertiary amide nitrogen coordination is observed in 5; this gives rise to significantly reduced cis-trans isomerization barriers. Possible implications for metal-induced conformational changes in proteins are discussed. PMID- 11775687 TI - From V8Ga36.9Zn4.1 and Cr8Ga29.8Zn11.2 to Mn8Ga27.4Zn13.6: a remarkable onset of Zn-cluster formation in an intermetallic framework. AB - The series of isotypic compounds V8Ga41 --> V8Ga36.9Zn4.1 --> Cr8Ga29.5Zn11.2 --> Mn8Ga27.4Zn13.6 with the V8Ga41 structure type (space group R3, Z = 3) was prepared and structurally characterised by X-ray diffraction experiments (V8Ga41: a 13.9351(5), 14.8828(12); V8Ga36.9Zn4.1: a = 13.9244(7), c = 14.8660(9): Cr8Ga29.8Zn11.2: 13.7153(5), c = 14.6872(9); Mn8Ga27.4Zn13.6: a = 13.6033(6), c = 14.6058(16)). The site occupancies of the ternary compounds were refined from neutron powder-diffraction data and exposed a startling segregation of Zn and Ga, which finally resulted in the formation of separated Zn13 cluster entities corresponding to almost ideal centred cuboctahedra or small pieces of fcc metal in the Mn compound, which has the highest Zn content in the series. The homogeneity ranges of the underlying phases T8Ga41 xZnx were determined to be 0 < x < 4.1(3), 8.7(3) < x < 11.2(3) and 13.6(4) < x < 16.5(3) for T = V, Cr and Mn, respectively. The different ranges of composition of the phases reflect the requirement of an optimum electron concentration for a stable V8Ga41-type structure, which is in the narrow range between 159 and 165 electrons per formula unit. First-principles electronic-structure calculations could explain this fact by the occurrence of a pseudo gap in the density of states at which the Fermi level is put for this particular electron concentration. Furthermore the nature of the Zn/Ga segregation was revealed: T-Zn interactions were found to be considerably weaker than those for T-Ga. This places the Zn atoms as far as possible from the T atoms, thus leading to the formation of cuboctahedral Zn13 entities. PMID- 11775688 TI - Nanotube formation by hydrophobic dipeptides. AB - A wide range of applications has been suggested for peptide-based nanotubes, which first attracted considerable interest as model systems for membrane channels and pores. The intriguing and unprecedented observation of nanotube formation by supramolecular self-assembly of the four dipeptides L-Leu-L-Leu, L Leu-L-Phe, L-Phe-L-Leu and L-Phe-L-Phe is described here. These simple compounds crystallize with hydrogen-bonded head-to-tail chains in the shape of helices with four to six peptide molecules per turn. The resulting structures have chiral hydrophilic channels with a van der Waals' diameter up to 10 A. PMID- 11775689 TI - Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio. AB - 1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu(dota-tetraamide)(H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: k298(ex)=9.4+/-0.2 x 10(3) s(-1) for [Eu(dotam)(H2O)]3+, 8.2+/-0.2 x 10(3) s(-1) for [Eu(dtma)(H2O)]3+ and 11.2+/-1.4 x 10(3) s(-1) for [Eu(dotmam)-(H2O)]3+; m: k298(ex)=474+/-130 x 10(3) s(-1) for [Eu(dotam)(H2O)3+, 357+/-92 x 10(3) s(-1) for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: deltaV++ = +4.9 cm3 mol(-1) for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol(-1) for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by a-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential Gd(III)-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate. PMID- 11775690 TI - Solid-state transformations of zinc 1,4-benzenedicarboxylates mediated by hydrogen-bond-forming molecules. AB - The zinc 1,4-benzenedicarboxylates [Zn3(bdc)3(H2O)3] . 4 DMF (1; bdc = 1,4 benzenedicarboxylate), [Zn(bdc)(H2O)] . DMF (2), and [Zn(bdc)] DMF (3) crystallise at room temperature from mixtures of toluene/ dimethylformamide (DMF) under concentrated, dilute and dry conditions, respectively. The structure of phase 1 (monoclinic: P2(1)/c, a 13.065(1), b = 9.661(1), c = 18.456(1) A, beta = 106.868(2) degrees) consists of layers containing stacks of three zinc cations linked by mono- and bidentate bdc groups. Structure 1 converts to the known phase 2 by an irreversible, reconstructive phase transformation, whereas 2 and 3 interconvert reversibly upon the loss or addition of water. Removal of all solvent molecules included during crystallisation gives poorly crystalline [Zn(bdc)] (4), which is readily converted to highly crystalline solids upon contact with hydrogen-bond-forming molecules such as water, DMF and small alcohols. The crystal structures of the mono- and dihydrates [Zn(bdc)(H2O)] (6) and [Zn(bdc)-(H2O)2] (7) have been determined ab initio from powder X-ray diffraction data (compound 6, monoclinic: C2/c, a = 17.979(1), b = 6.352(1), c = 7.257(1) A, beta=91.477(1) compound 7, monoclinic: C2/c, a = 14.992(1), b = 5.0303(2), c = 12.098(1) A, beta = 103.82(1) degrees). The methanol adduct [Zn3(bdc)3] . 6CH3OH (5) is the same as that prepared previously by direct crystallisation. Comparison of these adduct structures with those prepared directly reveal that they are formed by in situ recrystallisations. Subsequent removal of included molecules gives amorphous [Zn(bdc)], which can be recrystallised again when placed in contact with hydrogen-bond-forming molecules. PMID- 11775691 TI - Highly selective guest uptake in a silver sulfonate network imparted by a tetragonal to triclinic shift in the solid state. AB - The silver sulfonate network presented herein, silver 3-pyridinesulfonate, reversibly and selectively absorbs MeCN while undergoing a major structural rearrangement. The origin of this structural flexibility is a coupling of the weak coordinating ability of the SO3 group with the geometrically pliant silver(I) center. Single crystal and powder X-ray structures of both the desolvated and solvated forms are presented in addition to the mechanism of their reversible interconversion. A heterogeneous gas chromatographic study showing selective extraction of the MeCN is also presented. Extended solid frameworks which reorder to any extent are not common but the structure presented herein transforms from a tetragonal to a triclinic crystal system. The results indicate that cooperative interactions in systems based on supposedly weaker interactions can yield softer yet functional networks with behavior unlike that observed in more rigid inorganic frameworks. PMID- 11775692 TI - Alpha-homo-DNA and RNA form a parallel oriented non-A, non-B-type double helical structure. AB - Cross-talking between nucleic acids is a prerequisite for information transfer. The absence of observed base pairing interactions between pyranose and furanose nucleic acids has excluded considering the former type as a (potential) direct precursor of contemporary RNA and DNA. We observed that alpha-pyranose oligonucleotides (alpha-homo-DNA) are able to hybridize with RNA and that both nucleic acid strands are parallel oriented. Hybrids between alpha-homo-DNA and DNA are less stable. During the synthesis of alpha-homo-DNA we observed extensive conversion of N6-benzoyl-5-methylcytosine into thymine under the usual deprotection conditions of oligonucleotide synthesis. Alpha-homo-DNA:RNA represents the first hybridization system between pyranose and furanose nucleic acids. The duplex formed between alpha-homo-DNA and RNA was investigated using CD, NMR spectroscopy, and molecular modeling. The general rule that orthogonal orientation of base pairs prevents hybridization is infringed. NMR experiments demonstrate that the base moieties of alpha-homo-DNA in its complex with RNA, are equatorially oriented and that the base moieties of the parallel RNA strand are pseudoaxially oriented. Modeling experiments demonstrate that the duplex formed is different from the classical A- or B-type double stranded DNA. We observed 15 base pairs in a full helical turn. The average interphosphate distance in the RNA strand is 6.2 A and in the alpha-homo-DNA strand is 6.9 A. The interstrand P-P distance is much larger than found in the typical A- and B-DNA. Most helical parameters are different from those of natural duplexes. PMID- 11775693 TI - Dinuclear diazene iron and ruthenium complexes as models for studying nitrogenase activity. AB - The strength of hydrogen bonds has been investigated in various dinuclear diazene FeII, FeIII, and RuII complexes by use of the recently developed shared-electron number approach. Hydrogen bonding in these compounds plays an essential role in view of designing a model system for nitrogenase activity. The general conclusions for iron-sulfur complexes are: hydrogen bonds can stabilize diazene by at least 20% of the total coordination energy; the strength of the hydrogen bonds can be directly controlled through the hydrogen-sulfur bond length; reducing FeIII centers to FeII can double the hydrogen bond energy. PMID- 11775694 TI - Regiocontrolled one-step synthesis of 3,3'-disubstituted 2,2'-bipyridine ligands by cobalt(I)-catalyzed cyclotrimerization. AB - A one-step, regioselective synthesis of annelated symmetric and asymmetric 3,3' disubstituted 2,2'-bipyridines by cobalt(I)-catalyzed [2+2+2] cycloadditions between 5-hexynenitrile and 1,3-diynes is described. In the symmetric case, the total regioselectivity of the first cycloaddition is ensured electronically by the conjugation of the triple bonds, and for aminomethylated diynes that of the second is ensured by the cobalt coordinating to the aminomethyl rather than to the hexynenitrile nitrogen. In the asymmetric case, the first cycloaddition took place chemoselectively, which in the case of bis(trimethylsilyl)-1,3,5-hexatriyne (viewed as a 1,3-diyne) is explained by semiempirical calculation of LUMO coefficients. The copper(I) complex of 6b, constituting the first reported complex of the form ML2 (L is a symmetric 3,3'-disubstituted 2,2'-bipyridine), has been prepared. It had UV/Vis and NMR spectra reflecting the 3-substituent induced mutual torsion of the bipyridine rings in the cis conformation, as was confirmed by x-ray diffractometric determination. The bipyridine 6c forms the dinuclear complex [Cu2(6c)2(CH3CN)2]2+ in the solid state. PMID- 11775695 TI - Reversible fixation of carbon dioxide at nickel(0) centers: a route for large organometallic rings, dimers, and tetramers. AB - The reaction between bis(cycloocta-1,5-diene)nickel(0), carbon dioxide and benzaldehyde-N-furfurylideneimine (A) in 1,4-dioxane or THF results in the formation of the 24-membered organometallic macrocycles of the type [(A)Ni( CH(R1)-N(R2)-COO-)]6(solv)n (R1: phenyl, R2: furfurylidene, solv: 1,4-dioxane in 1a, THF in 1b). According to the X-ray analyses, six monomeric nickelacyclic units are connected through six Ni-mu2-OCO-Ni bridges in these macrocycles. The cavities of the metallomacrocycles (diameter: 9.410(1) A in 1a, 9.250(1) A in 1b) each contain one solvent molecule. Reaction of 1b with Me3P results in the displacement of the peripheral ligands A by the phosphine to form the 24-membered organometallic macrocycle 1c. Both 1a and 1b isomerize in benzene to form the dimeric complex [(A)Ni(-CH(R1)-N(R2)-COO-)]2(solv)n (2). The X-ray crystal structure reveals that 2 consists of the same monomeric units as found in 1a and 1b. However two Ni-mu2-O-Ni bonds link the carboxylato groups. The solvent dependent isomerization of 1b yielding 2 is a reversible reaction. Furthermore, the macrocycle 1b partially eliminates carbon dioxide above 20 degrees C, followed by elimination of half of the monodentately coordinated Schiff base ligands to form the planar tetrameric complex 6. This is also a reversible process. PMID- 11775696 TI - A novel dinuclear ruthenium complex bridged through a substituted phenazine ligand formed by ruthenium-promoted oxidative assembly of 1,3-diaminobenzene. AB - The reaction of [Ru(acac)3] (acac = acetylacetonate) with molten 1,3 diaminobenzene affords the crystalline monometallic compound [Ru(L1)-(acac)21 (1: L1 = N-(3'-aminophenyl)1,2-(3-amino)benzoquinone diimine) along with an unstable dimetallic compound [Ru2(mu-L2)(acac)4] (2: L2=N-4,6-bis(3'-aminophenyl)imino-3,5 diimino-hex-1-ene). Compound 2 transforms to a stable dimetallic compound [Ru2(mu L3)(acac)4] (3: L3 = 2-amino-6(3'-aminophenyl)imino-9-imino-phenazine) in boiling 2-methoxyethanol. The above compounds are formed by ruthenium-mediated oxidative di- or trimerization of the diamine with the formation of several new C-N bonds. The products have been thoroughly characterized. FAB mass spectra, along with other physicochemical data, were used for their formulations. The compounds 1, 2, and 3 display intense peaks due to their parent molecular ions at m/z 512, 916, and 914, respectively. Final characterization of complex 3 was made by single crystal X-ray structure determination. The structure of 3 confirmed the formation of three new C-N bonds and the bridging ligand L3 from 1,3-diaminobenzene. The conversion, 2 --> 3 is an oxidative ring-closure reaction, which is associated with dehydrogenation reactions. The monometallic compound 1, showed a reversible metal-based anodic response at 0.35 V. On the other hand, both the compounds 2 and 3 showed a pair of well-resolved metal-based anodic oxidations, for which the separation between the two successive anodic responses were high (>0.4 V). In addition, all of them showed multiple cathodic responses that were in the range 1.0 to -2.0 V. PMID- 11775697 TI - The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification. AB - The fine-tuned operation of the nervous system is accomplished by a diverse set of neurons which differ in their morphology, biochemistry and, consequently, their functional properties. The accurate interconnection between different neuron populations and their target tissues is the prerequisite for physiologically appropriate information processing. This is exemplified by the regulatory action of the autonomic nervous system in vertebrates to sustain homeostasis under changing physiological demands. For this purpose, the coordination of divergent regulatory responses is required in a multitude of tissues spread over the entire body. To meet this task, diverse neuronal populations interact at different levels. In the sympathetic system. chemical relations between preganglionic and postganglionic neurons appear to differ along the rostrocaudal axis. In addition, postganglionic neurons innervating different target tissues at a segmental level have distinct properties. Differences in their preganglionic innervation and their integrative membrane properties result in diverse activation patterns upon reflex stimulation. Moreover, postganglionic neurons differ in the transmitter molecules they employ to convey information to the target tissues. The segregation of noradrenaline and acetylcholine to different populations of postganglionic sympathetic neurons is well established. A combination of cellular and molecular approaches has begun to uncover how such a complex system may be generated during development. Growth and transcription factors involved in noradrenergic and cholinergic differentiation are characterised. Interestingly, they can also promote the expression of proteins involved in transmitter secretion. As the proteins participating in the vesicle cycle are expressed in many neuron populations, whereas the enzymes of transmitter biosynthesis are restricted to subpopulations of neurons, the findings suggest that early in neuronal development subpopulation-specific and more widely expressed neuronal properties can be commonly induced. Still, many details concerning the signals involved in the induction of the neurotransmitter synthesis and release machinery remain to be worked out. Likewise, the regulatory processes resulting in differences of electrophysiological membrane properties and the specific recognition between pre- and postganglionic neurons have to be determined. Ultimately, this will lead to an understanding at the molecular level of the development of a nervous system with diverse neuronal populations that are specifically interconnected to distinct input neurons and target tissues as required for the performance of a complex regulatory function. PMID- 11775698 TI - Zinc sulphate-induced anosmia decreases the nerve fibre density in the anterior cerebral artery of the rat. AB - Detailed quantitative studies have demonstrated a topographical heterogeneity of nerve fibre densities in the cerebral arteries at the base of the brain as well as local changes in ageing and Alzheimer's patients. In this study, we test the hypothesis that local patterns of innervation are influenced by changes in flow fluctuations. This was investigated by inducing chronic anosmia and monitoring the nerve fibre density in the basal cerebral arteries in the adult rat. The olfactory epithelium was examined after staining with hematoxylin and eosin and showed a marked reduction of thickness in the anosmic group compared to the control group. The olfactory bulb was histochemically stained for succinate dehydrogenase (SDH) activity and showed a reduced staining in the anosmic group compared to the controls. Whole mount preparations of the basal cerebral arteries were immunostained for the general neural marker protein gene product (PGP) 9.5. The nerve fibre densities of the vessel walls were quantified by image analysis and expressed as area percentage and intercept density. This analysis showed a significant reduction in area percentage for the first part of the anterior cerebral artery, as well as for the second part of the anterior cerebral artery, and a significant reduction in intercept density for the second part of the anterior cerebral artery in the anosmic group. We conclude that peripherally induced anosmia decreases nerve fibre density in the anterior cerebral artery that may be due to a decreased metabolic activity in the rhinencephalon and, as a consequence, a reduction of flow fluctuations in the blood vessels supplying this area occurs. PMID- 11775699 TI - Facial immersion bradycardia in teenagers and adults accustomed to swimming. AB - We compared heart rate and breath-hold duration during facial immersion in teenagers, 11-14 years (N = 6), 15-18 years (N = 6) and adults, 33-48 years (N = 11). The subjects were members of a competitive swimming club, and were familiar with facial immersion. In contrast to the results of a previous study (J. Appl. Physiol. 63 (1987) 665) in which naive subjects were used, the 11-14 group were able to breath-hold as long as adults (mean +/- SE, 47+/-6 vs. 46+/-4 s). This allowed time for the full development of bradycardia. Pre-immersion heart rate was significantly higher in young teens than in adults (100+/-4 vs. 78+/-3 b.p.m.). Heart rate after 30 s of head immersion was statistically identical (young teens, 65+/-5 b.p.m.; adults, 64+/-3 b.p.m.). Therefore, both the percentage reduction from pre-immersion rate and rate of fall in heart rate were greater in 11-14-year-olds than in adults. Oxygen loading increased breath-hold time in all groups, and slowed the onset of bradycardia in adults and older teens, but not in the 11-14-year-old group, during the first 10 s after immersion. We conclude that breath-hold time in teenagers is influenced by familiarity with underwater breath-holding. The resulting cardiovascular adjustments in 11-14-year-olds are intrinsically at least as intense as those in adults and seem to have a faster onset. PMID- 11775700 TI - Percutaneous transluminal mitral valvuloplasty improves cardiopulmonary baroreflex sensitivity in patients with mitral stenosis. AB - Patients with heart failure frequently have increased sympathetic tone, which could result in part from impairment of the inhibitory influence of cardiopulmonary baroreflexes. Percutaneous transluminal mitral valvuloplasty (PTMV) provides a unique model for evaluating functional changes in cardiopulmonary baroreflexes without open-heart surgical manipulation. We examined the effects of PTMV on cardiopulmonary baroreflexes and sympathetic nerve activity in 10 patients with mitral stenosis. We measured muscle sympathetic nerve activity using microneurography. Cardiopulmonary baroreflex provocation was performed by applying a lower body negative pressure of -10 mm Hg, and its sensitivity was determined by dividing the percent change in muscle sympathetic nerve activity by the change in central venous pressure. Response to isometric exercise was assessed by handgrip at 30% of maximal voluntary contraction for 3 min. PTMV significantly increased mitral valve area and cardiac index and decreased mean left atrial pressure. PTMV significantly decreased burst rate from 25.1+/-2.5 to 15.6+/-2.6 bursts/min (p < 0.01) and burst incidence from 37.1+/-3.7 to 23.6+/-3.3 bursts/100 heart beats (p < 0.01). After PTMV, cardiopulmonary baroreflex sensitivities measured using burst rate and burst incidence were -39.9+/-4.9%/mm Hg and -38.7+/-6.2%/mm Hg, respectively, which were significantly steeper than those before PTMV (-9.2+/-1.1%/mm Hg and -8.4+/ 1.1%/mm Hg; p < 0.01). There were significant correlations between muscle sympathetic nerve activity at rest and cardiopulmonary baroreflex sensitivity. PTMV did not affect muscle sympathetic responses to handgrip exercise. These results suggest that patients with mitral stenosis have baseline sympathetic nerve activation, which could result in part from impaired cardiopulmonary baroreflexes. PMID- 11775701 TI - Life-threatening orthostatic hypotension in a case with bulbo-myelo-radiculo neuropathy. AB - A 59-year-old female developed acute autonomic failure accompanied by life threatening orthostatic hypotension. Reduced plasma noradrenaline levels and enhanced pressure response to noradrenaline infusion were compatible with a diagnosis of acute pan-dysautonomia. However, nerve conduction tests clearly revealed motor and sensory nerve involvement and abnormal F-responses. A sural nerve biopsy and catecholamine fluorescence study of the rectal mucosa revealed relatively preserved postganglionic unmyelinated nerve fibers. Six weeks later, the patient developed another episode of bulbar palsy and right hemiparesis; the MRI showed lesions in the medulla oblongata and right cervical spinal cord. The prognosis of acute pan-dysautonomia is usually unsatisfactory, but the present patient showed good steroid-responsiveness probably because impaired preganglionic sympathetic myelinated fibers and medulla oblongata recovered quickly. PMID- 11775702 TI - Brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats. AB - The rat L5/6 facet joint is innervated from L1 to L6 by the dorsal root ganglia (DRG). The presence of substance P- and calcitonin gene-related peptide immunoreactive (ir) DRG neurons innervating the L5/6 facet joint has been demonstrated. However, the presence of brain-derived neurotrophic factor (BDNF) ir and the vanilloid receptor subtype 1 (VR1)-ir DRG neurons, which relate to inflammatory and burning pain innervating the L5/6 facet joint, has not. Fluoro gold (FG)-labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs from T13 to L6 levels. Of the FG-labeled neurons, the proportions of BDNF-ir in L1, L2, L3, L4 and L5 DRG neurons were 9%, 15%, 21%, 17% and 20% and the proportions of VR1-ir L1, L2, L3, L4 and L5 DRG neurons were 8%, 9%, 15%, 16% and 15%, respectively. PMID- 11775703 TI - Neuronal connections of the paratrigeminal nucleus: a topographic analysis of neurons projecting to bulbar, pontine and thalamic nuclei related to cardiovascular, respiratory and sensory functions. AB - The paratrigeminal nucleus, which receives sensory input from trigeminal, glossopharyngeal and vagus nerves, has efferent projections to bulbar, pontine and possibly to thalamic structures associated with nociception, thermoregulation and cardiovascular control. Anterograde neuronal tracers were used to study paratrigeminal efferent connections. Labeled terminal fibers, evidencing bilateral efferent paratrigeminal projections were observed in the medial and caudal solitary tract (sol), lateral reticular nucleus (LRt), ambiguus nucleus (Amb), rostroventrolateral reticular nucleus (RVL), while ipsilateral projections were found in the parabrachial (PB) nuclei and ventral portion of the ventral posteromedial thalamic nucleus (VPM). This extends other findings that describe paratrigeminal projections. Retrograde neuronal transport tracers, microinjected in the defined projection areas were used to map distribution of the paratrigeminal neurons originating different efferent connections. Microinjection of latex microspheres containing fluorescein or rhodamine and Fluoro-gold in the ventral VPM, PB, RVL, Amb, LRt and NTS revealed sets of labeled paratrigeminal nucleus neurons respectively organised in a rostral-caudal sequence. The largest extent of the paratrigeminal nucleus (medial portion) contained neurons projecting to the RVL/Amb, structures associated with cardiovascular regulation. The data show a segmented topographical organization of the nucleus, with different sets of neurons within delimited segments, projecting to neuronal structures associated with different functions. This points to a complex and extensive role for the paratrigeminal nucleus in the integration of somatosensory reflexes related to cardiovascular, respiratory and pain mechanisms. The nucleus may act as a medullary relay interposed between sensory afferents and different structures related to homoeostatic functions. PMID- 11775704 TI - Local capsaicin application to the stellate ganglion and stellatectomy attenuate neurogenic inflammation in rat bronchi. AB - The present study investigated the contributions of vagal and nonvagal sensory nerve fibers on neurogenic inflammation in rat bronchial airways. A surgical procedure was developed via the rat mediastinum ventral intercostal space to prepare an intercostal opening without causing pneumothorax for performing stellate ganglionectomy alone, thoracic vagus nerve section alone, and stellatectomy plus thoracic vagotomy, and for injecting capsaicin (2 microl, 10 mg/ml) and 6-hydroxydopamine (2 microl, 50 mg/ml) into the ganglion. One week later in our procedure, we investigated if neurogenic inflammation induced by an intravenous injection of capsaicin (300 nmol/ml/kg) and innervation density of substance P-immunoreactive sensory axons could be decreased after chronic denervation in the rat lower airways. The major findings were that surgical removal of the right stellate ganglion and local capsaicin application resulted in a significant attenuation of neurogenic plasma extravasation in the right bronchial tree evoked by systemic capsaicin application. Reduction of neurogenic plasma extravasation was totally abolished by combined stellatectomy and thoracic vagotomy. The number of substance P-containing axons was also greatly decreased following these surgical and capsaicin treatments. It is concluded that sensory nerve fibers from both vagal source and nonvagal (spinal) source, which associated with the stellate ganglion, contributed significantly to neurogenic inflammation in the bronchial airways with a slightly higher contribution from the vagus nerve. PMID- 11775705 TI - Postnatal development of blood pressure and baroreflex in mice. AB - Postnatal development of blood pressure, heart rate and their regulation by arterial baroreceptor reflex in mice was examined. We first confirmed that simultaneous recordings of pulsatile blood pressure by the "servo null" method and the conventional catheter method gave almost identical tracings in halothane anesthetized adult mice. We then measured blood pressure by servo null method together with electrocardiograph in mice of various ages from newborn to adult. Mean blood pressure increased progressively with age from 19 + 2 mm Hg in P0 newborn to 74+/-1 in adult mice, while heart rate initially increased from 365+/ 12 bpm in newborn to 441+/-15 in infant (7 days old), and then decreased to 337+/ 15 in adult mice. Between 1 and 2 weeks of age, gain of arterial baroreceptor reflex abruptly increased from a newborn value of 0.3 to a near adult value of 1.1 ms/mm Hg. On the other hand, sensitivity to anesthesia did not differ except for P1 and P2 newborns. We conclude that pulsatile blood pressure can be accurately measured by the servo null method even in the newborn mice and that baroreflex heart rate control mature at around 2 weeks after birth in the mice. PMID- 11775706 TI - Marked miosis caused by deafferenting the oculomotor nuclear complex in the cat. AB - Animals show highly constricted pupils in certain conditions (e.g., coma). To know the anatomical basis for this miosis, mechanical separation of the oculomotor nuclear complex was done using four transections of the brain. Two frontal transections were placed rostral and caudal to the oculomotor nuclear complex. Two bilateral oblique transections were performed by aiming through the dorsal edge of the Edinger-Westphal nucleus at an angle of 50 degrees from the horizontal plane and vertical to the frontal plane. After the transections, we examined pupillary size for up to 2 weeks to exclude acute effects of deafferentiation. The transections were histologically examined. If the bilateral pupils were highly constricted after the transections, those pupils remained in the miotic state during the survival periods (4-14 days). The deafferented midbrain of the animals, which showed marked miosis, contained the intact oculomotor nuclear complex and nerves with the whole part of the midbrain ventral to them, but with only a small region dorsolateral to them. Given the previous finding that electrical microstimulation of the area ventral to the oculomotor nuclear complex and nerves has failed to elicit pupil constriction, our results suggest that the oculomotor nuclear complex itself could work as a generator for the strong activity of preganglionic pupilloconstrictor neurons. PMID- 11775707 TI - Role of autonomic nervous system for development and suppression of motion sickness in Suncus murinus. AB - To clarify the role of autonomic nervous function in motion sickness, the effect of agents that act on the autonomic nervous system on the motion stimuli-induced emesis was studied in two strains of Suncus murinus (Jic:SUN-Her and Jic:SUN-Ler) with congenitally different sensitivity to veratrine sulfate. We demonstrated significant differences between the two strains in sensitivity to motion stimuli. Isoproterenol (2.5 mg kg(-1), s.c.) significantly prolonged the latency to the first emetic episode induced by motion stimuli and significantly decreased the number of emetic episodes in Jic:SUN-Her suncus. Hexamethoium (2.0 mg kg(-1), s.c.) tended to shorten the latency in Jic:SUN-Ler. Acetylcholine (1.2 mg kg(-1), s.c.) enhanced the emetic response in Jic:SUN-Ler, but atropine (4.0 mg kg(-1), s.c.) suppressed motion stimuli-induced emetic response in Jic:SUN-Her. These results suggest that the predominance of parasympathetic nervous activity is relevant to the enhancement of motion stimuli-induced emetic response, whereas the predominance of sympathetic nervous activity suppresses motion stimuli induced emetic response. Norepinephrine (0.8 mg kg(-1), s.c.) enhanced motion stimuli-induced emesis contrary to isoproterenol in Jic:SUN-Ler although both drugs are adrenergic agents. However, atropine pretreatment (4.0 mg kg(-1), s.c.) inhibits norepinephrine-induced emetic response. It was considered that norepinephrine-induced emetic response might be dependent on a secondary increase of parasympathetic nervous activity due to bororeflex. Moreover, the different emetic response in Jic:SUN-Her and Jic:SUN-Ler suncus to motion stimuli and drug administration mentioned above indicated that different participation of autonomic nervous activity and/or afferent information from the baroreceptor in the emetic response may exist between these animal groups. PMID- 11775708 TI - Intrapericardial algogenic chemicals evoke cardiac-somatic motor reflexes in rats. AB - Many patients suffer from secondary muscle hyperalgesia after experiencing angina pectoris. Electrophysiological studies have also demonstrated electromyography (EMG) activities evoked during brief occlusion of the coronary artery in cats. Our objectives are: (1) to develop an animal model to study muscle changes resulting from cardiac dysfunction and (2) to investigate possible links between muscle hyperalgesia and EMG activities observed with ischemic heart diseases. Intrapericardial infusion of algogenic chemicals produced EMG activities in paraspinal muscles. Among these paraspinal muscles, the spinotrapezius produced the most consistent responses (38/53 animals). The evoked responses, in most cases, persisted longer than 90 s (29/53 muscles). The EMG activities consisted of three patterns of motor-unit discharge, namely single-unit, complex, and ventilation-related. The duration of the patterns, as well as the shape and amplitude of the motor-unit waveforms, are similar to the characteristics of muscle spasms. Since sensitization of muscle afferent fibers by noxious stimuli could produce angina-like pain, the spasm-like EMG activities might sensitize muscle afferent fibers that contribute to acute angina pain and secondary muscle hyperalgesia of cardiac patients. PMID- 11775709 TI - Phosphorylation of CREB in thoracolumbar spinal neurons and dorsal root ganglia after renal artery occlusion in rat. AB - These studies have demonstrated that ipsilateral renal artery occlusion (RAO) in rat results in the phosphorylation of cyclic AMP (cAMP) response element binding protein (p-CREB) in the thoracolumbar (T8-L2) spinal cord and associated dorsal root ganglia (DRG). p-CREB-immunoreactivity (IR) was expressed bilaterally in the thoracolumbar spinal cord, whereas expression in the DRG was ipsilateral relative to RAO. p-CREB-IR was primarily expressed in four distinct regions of the spinal cord: medial or lateral dorsal horn (MDH or LDH), dorsal commissural nucleus (DCN) and the region of the intermediolateral cell column (IML). After RAO, p CREB-IR was greatest in the T13-L2 spinal segments. Within the T13-L1 spinal segments, p-CREB-IR was greatest in the MDH, LDH and DCN and expression in each of these regions was comparable within a segment. Following RAO, there was a significant (p < or = 0.001) increase in the percentage (86-98%) of p-CREB-IR spinal neurons expressing choline acetyltransferase (ChAT)-IR (a marker of preganglionic neurons) in the IML of the T10, T12 and L1 spinal segments examined. After ipsilateral RAO, expression of p-CREB-IR was increased in the ipsilateral, T8-L2 DRG with the greatest number of p-CREB-IR dorsal root ganglion cells being located in the L1 dorsal root ganglion. Retrograde tracing with Fluorogold (FG) to label renal afferent cells in the DRG revealed a significant (p < or = 0.01) increase in the percentage (75-86%) of renal afferent cells expressing p-CREB-IR after ipsilateral RAO. These studies demonstrate that p-CREB IR is a useful tool for examining the distribution of spinal neurons and DRG involved in reflexes of renal origin. In addition, expression of p-CREB-IR may be coupled to late response genes that may exert long-term changes in neuronal function after RAO. PMID- 11775710 TI - Hypothalamic cholinergic regulation of body temperature and water intake in rats. AB - Without disturbing the behavior of unanesthetized rats, the perfusion of neostigmine through microdialysis probe into the anterior hypothalamus (AH), paraventricular nucleus (PVN) and lateral ventricle (LV) decreased body temperature and increased water intake. On the other hand, the perfusion into the supraoptic nucleus (SON) increased the body temperature. The perfusion of neostigmine increased the extracellular concentration of acetylcholine in the perfusion sites except LV. Changes, both decrease and increase, in body temperature and increase in water intake were correlated with increases in c-fos like immunoreactivity (Fos-IR) in the hypothalamus, pons and medulla. Distinct Fos-IR was found in the PVN, SON, median preoptic nucleus (MnPO), locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Co-administration of atropine with neostigmine completely suppressed the changes in the body temperature, water intake and Fos-IR, all of which were induced by the neostigmine perfusion into AH, PVN and SON. In the LV-perfused rats, on the other hand, co-administration of atropine and neostigmine only partially prevented body temperature reduction and still induced significant hypothermia. These results suggest that muscarinic receptor activation in specific regions of the hypothalamus and the activation of LC and NTS are implicated in the regulation of body temperature and water intake. Other receptor processes are involved in the LV-induced changes. PMID- 11775711 TI - Transient arterial occlusion raises enkephalin in the canine sinoatrial node and improves vagal bradycardia. AB - The C-terminal proenkephalin sequence, Methionine-enkephalin-arginine phenylalanine (MEAP), is abundant in the myocardium and when delivered into the sinoatrial (SA) node by microdialysis, the peptide had significant vagolytic activity. The study that follows was conducted to determine if an increase in endogenous nodal MEAP could be demonstrated during reduced nodal blood flow and was endogenous MEAP similarly vagolytic. Microdialysis probes were placed in the canine SA node and perfused at 5 microl per min. The SA node artery was occluded and released four times at 10-min intervals. The intermittent occlusions were followed by one or two prolonged occlusions (30 min). Vagally mediated bradycardia was compared before, during, and after occlusion of the artery. An increase in recovered MEAP (70-220 fmol) was recorded during each of the initial 10-min occlusions. MEAP returned to baseline during each subsequent 10-min reperfusion. There was a sustained increase in MEAP (110-150 fmol) during longer occlusions. Contrary to the hypothesis, the increased MEAP during arterial occlusion was coincident with improved vagal bradycardia. The improvement in vagally mediated bradycardia was highly reproducible and was observed again during a second 30-min occlusion. The improved vagal function was reversed or reduced, respectively, when naltrindole or glibenclamide was included in the microdialysis inflow during arterial occlusion. Although these observations suggested that opioid receptors and ATP-sensitive K+ channels might have been involved, only a single dose of each agent was practical. Therefore, the specificity of these two responses remains to be confirmed. In summary, the recovery of endogenous opioids from the sinoatrial node increased during reduced arterial perfusion of the node. Contrary to expectations, the increase in recovered endogenous opioids was accompanied byimproved rather than impaired vagal bradycardia. PMID- 11775712 TI - Failure of Ba2+ and Cs+ to block the effects of vagal nerve stimulation in sinoatrial node cells of the guinea-pig heart. AB - The aim of the study was to evaluate which ionic currents are modified in the sinoatrial node of guinea pigs when the vagus is stimulated. Responses of isolated atrial preparations to bilateral vagus nerve stimulation were examined. In bath-mounted preparations, 10-s trains of vagal stimulation (1-50 Hz) slowed the rate at which atrial contractions occurred. After the trains of stimuli, the force generated by each contraction was reduced. Both vago-inhibitory responses persisted in the presence of caesium (2 mM) and barium ions (1 mM). Vagal stimulation evoked a similar bradycardia in superperfused preparations in which intracellular recordings were made from pacemaker cells in the sinoatrial node. When pacemaking activity was abolished by adding the organic calcium channel antagonist nifedipine (1 microM) to the perfusate, vagal stimulation generated an inhibitory junction potential (IJP). Both the bradycardia and the amplitude of the inhibitory junction potential increased as the frequency of vagal stimulation was increased. The ability of vagal stimulation to produce inhibitory junction potentials was unaffected by the addition of caesium and barium ions to the perfusate. These observations suggest that the negative chronotropic and inotropic responses to vagal stimulation only minimally involve a muscarinically activated potassium current (I(KACh)) or changes in the hyperpolarization activated pacemaker current Ih. PMID- 11775713 TI - Psychological vulnerability to completed suicide: a review of empirical studies. AB - Retrospective research shows that close to 90 percent of suicides have a diagnosable psychiatric disorder; however, only a small proportion of individuals with psychopathology take their own lives. This article reviews the empirical literature on psychological vulnerability to completed suicide. A search of the MEDLINE and PsycINFO databases yielded 46 cohort or case-control studies that used standardized or structured assessments of psychological dimensions. Five constructs have been consistently associated with completed suicide: impulsivity/aggression, depression, anxiety, hopelessness, and self consciousness/social disengagement. Current knowledge of psychological vulnerability to completed suicide could inform social and neurobiological research, and thereby deepen understanding of suicide while potentially bridging these areas of study. PMID- 11775714 TI - Effective problem solving in suicide attempters depends on specific autobiographical recall. AB - The relationship between over-general autobiographical memory and interpersonal problem solving was investigated by comparing a group of suicide attempters with a nonsuicidal psychiatric control group and a normal control group. Results showed that suicide attempters were more over-general in memory and displayed significantly poorer problem solving than the other two groups. Furthermore, suicide attempters who were more over-general displayed greater deficits in problem solving. It was concluded that effective problem solving in suicide attempters depends on specific autobiographical recall. PMID- 11775715 TI - Does suicidal history enhance acceptance of other suicidal individuals? AB - Suicide is stigmatized, so suicidal people may be especially hard to accept. To see if moderately suicidal outpatients were more accepting of a suicidal person than never-suicidal or severely suicide outpatients, 105 respondents completed measures of suicidality, depression, acceptance, and empathy. A curvilinear ANCOVA was nonsignificant, but a linear ANCOVA significantly adjusted for depression, and indicated, unexpectedly, that net of depression, never-suicidal people were more accepting of a suicidal person than moderately or severely suicidal people. Empathy and acceptance were moderately related. An implication is that social support for suicidal individuals might best be obtained from those who were never suicidal themselves. PMID- 11775716 TI - Childhood maltreatment and college students' current suicidal ideation: a test of the hopelessness theory. AB - Few studies have examined the relation between childhood maltreatment and adult suicidality within the context of a coherent theoretical model. The current study evaluates the ability of the hopelessness theory of depression's (Abramson, Metalsky, & Alloy, 1989) etiological chain to account for this relation in a sample of 297 undergraduates. Supporting the model, emotional, but not physical or sexual, maltreatment was uniquely related to average levels of suicidal ideation across a 2.5-year follow-up. Further, students' cognitive styles and average levels of hopelessness partially mediated this relation. Although these results cannot speak to causality, they support the developmental model evaluated. PMID- 11775717 TI - Suicidal ideation in Hispanic and mixed-ancestry adolescents. AB - This survey examined differences in suicidal ideation, depressive symptomatology, acculturation, and coping strategies based on ethnicity. The author gathered data from a self-report questionnaire administered to students in an ethnically diverse middle school (grades 6-8, N= 158). Hispanic (predominantly Mexican American) and mixed-ancestry adolescents displayed significantly higher risk of suicidal ideation compared to Anglo peers, even when socioeconomic status, age, and gender were controlled for. Suicidal ideation was associated with depressive symptoms, family problems, lower levels of acculturation, and various coping strategies. Using multivariate analysis, Hispanic ancestry, depressive symptoms, family problems, and the use of social coping remained in the model. PMID- 11775718 TI - Group intervention for widowed survivors of suicide. AB - This study evaluates the effects of two group interventions, the Bereavement Group Postvention (BGP) and the Social Group Postvention (SGP), on the bereavement outcomes in widowed survivors of suicide. The goals were to determine if the group interventions would significantly decrease levels of depression, psychological distress, and grief, as well as significantly increase the level of social adjustment among widowed survivors of suicide. Sixty widowed survivors of suicide were randomized to either the BGP or SGP intervention for 1-1/2 hour weekly sessions over an 8-week period. Study participants were recruited through various media and community referrals and initiated telephone contact with the study investigators. Statistically significant changes were found on all measures when the SGP and the BGP were combined for analyses on posttreatment assessments at 3 to 5 days after completion of the group intervention, and 6 months and 12 months after the intervention. Participants experienced a significant reduction in overall depression, psychological distress, and grief, as well as an increase in social adjustment. Further research with tighter controls of confounding variables as well as the inclusion of a no-treatment control group is indicated. PMID- 11775719 TI - Evaluations of the quality of coping reported by prisoners who have self-harmed and those who have not. AB - Yufit and Bongar (1992) argued that a deficiency in coping skills is an important risk factor for suicidal behavior. Dear, Thomson, Hall, and Howells (1998) found that prisoners who had self-harmed in the past 3 days were less likely than a comparison group to have used problem-solving or active cognitive coping strategies to handle the most significant stressor of the past week, but it was not clear whether this represented a difference in the quality of coping responses used. In this study, three groups of blind raters (prisoners, prison officers, and forensic psychologists) rated the coping responses of the participants in Dear et al.'s study. The coping responses of self-harmers were judged less beneficial and more risky. Problem-solving strategies were most often cited as contributing to beneficial outcomes and the catharsis strategies employed by self-harmers were most often judged to be counterproductive. It remains unclear whether prisoners who self-harmed routinely employ poor quality coping strategies or if they simply used poor quality coping on this occasion. PMID- 11775720 TI - Violent death among intimate partners: a comparison of homicide and homicide followed by suicide in California. AB - This study examines all intimate partner homicides in California during 1996 (N=186), and differences between intimate partner homicides with and without perpetrator suicide are compared. The study found that 40 percent of perpetrators committed suicide subsequent to the homicide. Variables examined in the analysis include type of weapon used, race, age, sex of perpetrators and victims, and location of the homicide. Significant differences were found between homicides with perpetrator suicide and those without. The results lend support to previous research suggesting that intimate partner homicide and homicide followed by suicide have different characteristics and possibly distinct etiologies. PMID- 11775721 TI - Confidential death to prevent suicidal contagion: an accepted, but never implemented, nineteenth-century idea. AB - Nineteenth-century medical literature often admonished the popular press to limit reports of suicide, because of a belief that knowledge of another's suicide could stimulate some persons to kill themselves. An 1837 case report (perhaps the earliest attempt at a psychological autopsy in an American medical journal) is discussed, because it presciently clarifies the concept of psychological sensitization. Its study leads to documentation of two examples of falsified death certificates. The power to prevent publicity of suicide by not reporting it may have diminished efforts for newspaper restraint, as did editorial resistance and later acceptance of Emile Durkheim's (1897/1951) strongly expressed belief that reports of suicide did not cause an overall increase in suicide. Despite lack of success over the past two centuries, efforts to keep reports of self inflicted death confidential continue to flow from concern about suicidal contagion. Today, uncensored websites and books advocating suicide may limit the benefit of the U. S. Surgeon General's "call to action" to prevent suicide, which again supports voluntary media restraint in reporting suicide. PMID- 11775722 TI - Epiploic appendagitis and omental infarction. AB - Epiploic appendagitis and omental infarction are benign self-limiting disorders. They are uncommon, though more common than is generally assumed. In both diseases the main clinical symptom is non-specific focal abdominal pain, with a normal or moderately raised white blood cell count and erythrocyte sedimentation rate. These findings often mimic an abdominal surgical emergency, which leads to clinical misdiagnosis of more common conditions such as appendicitis or diverticulitis. This may result in an unnecessary laparotomy. Ultrasonography (US) and computed tomography (CT) show characteristic features in most patients, allowing a secure non-operative diagnosis. Patients correctly diagnosed can avoid an operation or costly observation in hospital. PMID- 11775723 TI - Information for surgical patients: implications of the World Wide Web. AB - OBJECTIVE: To sample the amount and scope of information available on the internet about three common surgical conditions, identify the sources, and to examine the relevance of the web to the surgical community. DESIGN: Internet search. SETTING: General hospital, Republic of Ireland. MATERIAL: Three arbitrarily chosen conditions were sought--varicose veins, inguinal hernia, and gallstones. Four commonly used search engines--Yahoo, Altavista, Excite and Lycos, were used to search worldwide, and then sites restricted to the UK and Republic of Ireland. MAIN OUTCOME MEASURES: Quality and quantity of information available. RESULTS: All four search engines retrieved patient-orientated information on the three conditions. The sites accessed from the web page matches generally presented a comprehensive summary of the condition including aetiology, risk factors and clinical features, but gave variable amounts of information on treatment options, surgical complications, comparisons between treatments, and expected outcomes. Online health magazines provided most of the information sites. CONCLUSION: The internet offers easily-accessible patient-orientated information. Surgeons should make more use of it to satisfy patients' increasing need for information. PMID- 11775724 TI - Microheterogeneous changes of the C1-esterase inhibitor in plasma cannot predict operability, postoperative complications, or recurrence in cancer surgery. AB - OBJECTIVE: To find out if microheterogeneous changes--such as in molecular weight, isoelectric point, electrophoretic mobility, lectin binding or complexation of the C1-esterase inhibitor--exist in plasma samples from various subgroups of patients. If so, whether these differences could be used diagnostically in single plasma samples from patients with cancer for prognostic assessment of operability or risk of recurrence, and whether any change indicated an increased risk for development of postoperative complications. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 16 patients operated on as emergencies for acute peritonitis, 118 patients electively operated on for benign diseases, 274 patients electively operated on for cancer, and 212 patients admitted with acute abdominal pain. MAIN OUTCOME MEASURES: Curative operation, diagnoses, postoperative complications, recurrence of cancer within 2 years. RESULTS: There were no biochemical differences in the C1-esterase inhibitor between single or sequential plasma samples from four large groups of patients with benign disease, cancer, or inflammatory disease, with operable or inoperable cancer, with postoperative complications or not, or with or without early recurrence of cancer. CONCLUSIONS: Specialised biochemical analyses of C1 esterase inhibitor, the most important plasma protease inhibitor of the complement and kinin systems and of contact activation in plasma, cannot be used for prognostic assessment of operability, risk of postoperative complications, or risk of recurrence in patients with cancer. PMID- 11775725 TI - Effect of methylene blue on resuscitation after haemorrhagic shock. AB - OBJECTIVE: To compare prehospital hypotensive resuscitation with volume resuscitation, and find out whether reagents that inhibit free-oxygen radical formation, such as methylene blue, can improve resuscitation and survival. DESIGN: Randomised controlled trial. SETTING: Animal laboratory, Israel. ANIMALS: 48 adult male Wistar rats. INTERVENTIONS: After 30 minutes of controlled haemorrhage, rats were subjected to 60 minutes of uncontrolled haemorrhage with simultaneous resuscitation. Hartmann's solution alone, or with blood or with a bolus of methylene blue were infused to maintain the mean arterial pressure (MAP) at 80 or 40 mm Hg. Then haemorrhage was stopped and Hartmann's solution plus whole blood were infused to obtain a MAP that was within normal limits. MAIN OUTCOME MEASURES: Volumes of shed blood and resuscitation fluids, MAP, packed cell volume, blood pH and base deficit, and survival. RESULTS: During uncontrolled haemorrhage. a MAP of 80 mm Hg could not be reached in animals resuscitated with Hartmann's solution alone, and all died. All the rats given Hartmann's solution with a bolus of methylene blue or with whole blood achieved a higher MAP. MAP of 40 mm Hg was attained in all animals regardless of the resuscitation fluid. Only 15 of 24 animals resuscitated to a MAP of 80 mm Hg survived, compared with 22 survivors of the 24 rats resuscitated to a MAP of 40 mm Hg (p <0.04). Methylene blue or whole blood drastically reduced the volumes of shed blood and of fluids required, and moderated the reduction in packed cell volume, particularly during hypotensive resuscitation. CONCLUSION: Hypotensive protocols should be used to improve survival. Methylene blue given with the electrolyte solutions could negate their detrimental effects during resuscitation. PMID- 11775726 TI - Increasing prevalence of adenocarcinoma of the oesophagus and gastro-oesophageal junction: a study of the Swedish population between 1970 and 1997. AB - OBJECTIVE: To see whether there was an increasing incidence of adenocarcinoma of the oesophagus and gastric cardia in the Swedish population. If there is a rising trend and variations in it can be found, could it be explained as a period or cohort phenomenon? The data were also compared with the incidence of squamous cell carcinoma and gastric cancer with the gastric cardia excluded. DESIGN: Retrospective study. SETTING: Sweden. SUBJECTS: Swedish population. MAIN OUTCOME MEASURES: Age standardised incidence for each sex was calculated using the age distribution of the world population as a reference. Age-period-cohort models were fitted to data using Poisson regression to model log incidence rates. RESULTS: For the combined group of adenocarcinoma in the oesophagus and gastric cardia age standardised incidence gradually increased during the study period. The median increase between adjacent five-year intervals was 20% in women and 14% in men. A period effect was evident in men. CONCLUSION: This study shows that the incidence of adenocarcinoma of the oesophagus and gastroesophageal junction is rising for both men and women in the Swedish population. This is explained as a period effect. As well as previously-described risk factors such as gastro oesophageal reflux, obesity, and smoking, the increasing incidence can be explained as a shift in classification from squamous cell carcinoma to adenocarcinoma after 1985. PMID- 11775727 TI - Evolution of the need for operation for peptic pyloric stenosis over a period of 24 years (1976-1999). AB - OBJECTIVE: To analyse the need for operation for pyloric stenosis caused by duodenal ulcer over a period of 24 years (1976-1999). DESIGN: Retrospective study. SETTING: University hospital, Spain. SUBJECTS: 156 patients operated on for peptic pyloric stenosis. MAIN OUTCOME MEASURES: The number of patients operated on yearly were grouped into 4-year periods for statistical comparison. RESULTS: The number of cases operated on each year steadily decreased between 1976 and 1999. In the 1988-1991 period there was a significant reduction (p <0.05), which continued over the next two 4-year periods, particularly the last (p <0.01). CONCLUSION: Although we cannot use this study to establish a direct relation between the decrease in the indication for operations for peptic pyloric stenosis and the use of H2 antagonists, proton pump inhibitors, or treatment to eradicate Helicobacter pylori, we did find a significance difference between the years before and after the introduction of these drugs. PMID- 11775728 TI - Effects of dopexamine on acute necrotising pancreatitis in rats. AB - OBJECTIVE: To examine the effects of dopexamine on pancreatic tissue oxygen tension (PtO2) and the extent of acinar injury in rats with acute necrotising pancreatitis DESIGN: Laboratory study. SETTING: Medical school, Turkey. ANIMALS: 68 Sprague Dawley rats. MAIN OUTCOME MEASURES: Cardiorespiratory measurements, pancreatic PtO2, effects on activity of serum amylase and concentration trypsinogen activation peptide (TAP). and histological picture. RESULTS: The four study groups (sham + saline, sham + dopexamine, acute pancreatitis and acute pancreatitis + dopexamine) were each divided into two; in 9 rats in each, pancreatic biochemistry was studied, and in the remaining 8 in each group serum biochemistry and histology were studied. The groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, packed cell volume, and serum amylase activity. The use of dopexamine increased pancreatic PtO2 in the sham + dopexamine group without the important blood pressure changes. The induction of pancreatitis resulted in a significant reduction in pancreatic PtO2 in the pancreatitis groups. The use of dopexamine did not increase pancreatic PtO2. There were no significant differences in plasma TAP concentration and the extent of acinar cell injury in the animals in the pancreatitis groups. CONCLUSION: Treatment with dopexamine does not improve the pancreatic microcirculation or reduce the extent of acinar cell injury in acute necrotising pancreatitis and is therefore unlikely to be of benefit in patients with pancreatitis. PMID- 11775729 TI - Effect of the diameter of the common bile duct on the incidence of bile duct stones in patients with recurrent attacks of right epigastric pain after cholecystectomy. AB - OBJECTIVE: To study the relationship between the diameter of the common bile duct and the incidence of bile duct stones in non-jaundiced patients with recurrent attacks of right epigastric pain after cholecystectomy. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 57 consecutive, non jaundiced patients admitted for elective endoscopic retrograde cholangiopancreatography (ERCP) because of attacks of right epigastric pain after cholecystectomy. INTERVENTIONS: Measurement of maximum diameter of the common bile duct and presence or absence of bile duct stones. MAIN OUTCOME MEASURES: Diameter of bile duct (10 mm or less was regarded as normal) and presence or absence of stones. RESULTS: 33 patients had normal-sized bile ducts and in 24 they were widened. Only 2/33 patients with normal-sized ducts (6%) had stones, compared with 11/24 (46%) with wide ducts (p = 0.0008). However, the degree of ductal dilatation did not seem to have any influence on the presence or absence of stones. CONCLUSION: Bile duct stones are unlikely after cholecystectomy in patients who are not jaundiced and have a normal-sized common bile duct. However, nearly half of the patients with a wide common bile duct had stones, but the degree of dilatation was not important. PMID- 11775730 TI - Randomised clinical trial of two bypass operations for unresectable cancer of the pancreatic head. AB - OBJECTIVE: To compare two different types of prophylactic gastric bypass in patients with cancer of the pancreatic head who were not suitable for curative resection. DESIGN: Prospective study. SETTING: University hospital, Turkey. SUBJECTS: 44 patients with unresectable cancer of the pancreatic head without duodenal obstruction who presented between May 1995 and June 2000 who were randomised into 2 groups. INTERVENTIONS: 22 patients had an antecolic, isoperistaltic gastrojejunostomy, jejunojejunostomy, and hepaticojejunostomy after cholecystectomy. The remaining 22 had a hepaticojejunostomy and antecolic, antiperistaltic gastrojejunostomy procedure after cholecystectomy. MAIN OUTCOME MEASURES: Mortality, morbidity, postoperative course, and survival. RESULTS: There were no significant differences between the groups in the incidence of postoperative complications, time until restoration of oral diet, relaparotomy rate, late upper gastrointestinal bleeding, mortality, duration of hospital stay, and survival. The isoperistaltic operation took significantly longer than the antiperistaltic operation (p < 0.001) and there was less delayed gastric emptying in the antiperistaltic group but not significantly so. Both operations caused a significant lengthening in the postoperative gastric emptying time (p = 0.04 and p = 0.01, respectively). CONCLUSION: Both procedures are suitable for patients with unresectable carcinoma of the pancreatic head without impending duodenal obstruction. There was a trend towards better clinical results with the isoperistaltic procedure. PMID- 11775731 TI - Histological assessment of colorectal adenomas by size. Are polyps less than 10 mm in size clinically important? AB - OBJECTIVE: To define the relative risk of malignant transformation in colorectal adenomas less than 10 mm in diameter. DESIGN: Prospective study. SETTING: District general hospital, UK. SUBJECTS AND MATERIALS: 1228 polyps detected endoscopically in 445 patients over the 10-year period 1989-1999. MAIN OUTCOME MEASURES: Site, size, histological type and dysplastic grade of polyp. RESULTS: 657 of the 1228 polyps were adenomas: 281 (43%) tubular, 339 (51%) tubulovillous and 37 (6%) villous. In the 357 adenomas less than 10 mm in diameter, 11 (3%) were severely dysplastic and 2 carcinomas were detected, though neither was less than 5 mm in size. The relative risk of malignancy or severe dysplasia in adenomas of 10 mm or more compared with those of less than 10 mm was 3.8 (p < 0.0001). CONCLUSIONS: Although severe dysplasia and malignancy do occur in adenomas less than 10 mm in size, they are rare in lesions of less than 5 mm. We recommend routine destruction of all polyps 5 mm or more in size, though it is not essential to remove those of less than 5 mm if they are kept under surveillance. PMID- 11775732 TI - Experimental use of the obturator internus muscle as a functioning pelvic floor muscle in dogs. AB - OBJECTIVE: To investigate the possibility of using the obturator internus muscle instead of the levator ani as a pelvic floor muscle. DESIGN: Experimental study. SETTING: Teaching hospital, Egypt. ANIMALS: 7 male and 3 female mongrel dogs. INTERVENTIONS: Through a para-anal incision both muscles were exposed; the levator ani was excised and the lower border of the obturator internus was mobilised and sutured to the anorectal junction, the vesical neck, and the vaginal fornix. MAIN OUTCOME MEASURES: Rectal and anal pressures and electromyographic (EMG) activity recorded before and during transposition, and 1, 3, and 6 months later. Histological examination of biopsy specimens taken from the levator ani before, and from the obturator internus before, and 3, 6, and 12 months after, transposition. RESULTS: Stimulation of the levator ani caused anal pressure to decline significantly (p < 0.05). Stimulation of the obturator internus did not change anal pressure before transposition but caused a decline after it. There was EMG activity in the levator ani at rest, but not in the obturator internus before transposition though it was evident by 6 months afterwards. Levator ani consisted of skeletal muscle fibres with smooth muscle fibres in places, whereas the obturator internus consisted of skeletal fibres alone. Six months after operation examination of the obturator internus showed the presence of some smooth muscle fibres. CONCLUSION: These results suggest that the obturator internus might be suitable both anatomically and physiologically to replace the levator ani. However, before it can be suggested as a treatment for levator dysfunction syndrome further experimental studies are necessary. PMID- 11775733 TI - Intussusception of the appendix by a villous adenoma. PMID- 11775734 TI - Natural killer cell deficiency and severe wound infection after thyroid surgery. PMID- 11775735 TI - Blunt tracheo-oesophageal transsection. PMID- 11775736 TI - Massive necrosis of the gastrointestinal tract after ingestion of hydrochloric acid. PMID- 11775738 TI - The solution structure of [d(CGC)r(amamam)d(TTTGCG)]2. AB - The solution structure and hydration of a DNA.RNA hybrid chimeric duplex [d(CGC)r(amamam)d(TTTGCG)]2 in which the RNA adenines were substituted by 2'-O methylated riboadenines was determined using two-dimensional NMR, simulated annealing, and restrained molecular dynamics. Only DNA residue 7T in the 2'-OMe RNA.DNA junction adopted an O4'-endo sugar conformation, while the other DNA residues including 3C in the DNA.2'-OMe-RNA junction, adopted C1'-exo or C2'-endo conformations. The observed NOE intensity of 2'-O-methyl group to H1' proton of 4am at the DNA.2'-OMe-RNA junction is much weaker than those of 5am and 6am. The 2'-O-methyl group of 4am was found to orient towards the minor groove in the trans domain while the 2'-O-methyl groups of 5am and 6am were found to be in the gauche (+) domain. In contrast to the long-lived water molecules found close to the RNA adenine H2 and H1' protons and the methyl group of 7T in the RNA-DNA junction of [d(CGC)r(aaa)d(TTTGCG)]2, there were no long-lived water molecules found in [d(CGC)r(amamam)d(TTTGCG)]2. This is probably due to the hydrophobic enviroment created by the 2'-O-methylated riboadenines in the minor groove or due to the wider minor groove width in the middle of the structure. In addition, the 2'-O-methylation of riboadenines in pure chimeric duplex increses its melting temperature from 48.5 degrees C to 51.9 degrees C. The characteristic structural features and hydration patterns of this chimeric duplex provide a molecular basis for further therapeutic applications of DNA.RNA hybrid and chimeric duplexes with 2'-modified RNA residues. PMID- 11775737 TI - Membrane-bound structure and alignment of the antimicrobial beta-sheet peptide gramicidin S derived from angular and distance constraints by solid state 19F NMR. AB - The antimicrobial properties of the cyclic beta-sheet peptide gramicidin S are attributed to its destabilizing effect on lipid membranes. Here we present the membrane-bound structure and alignment of a derivative of this peptide, based on angular and distance constraints. Solid-state 19F-NMR was used to study a 19F labelled gramicidin S analogue in dimyristoylphosphatidylcholine bilayers at a lipid:peptide ratio of 80:1 and above. Two equivalent leucine side chains were replaced by the non-natural amino acid 4F-phenylglycine, which serves as a highly sensitive reporter on the structure and dynamics of the peptide backbone. Using a modified CPMG multipulse sequence, the distance between the two 19F-labels was measured from their homonuclear dipolar coupling as 6 A. in good agreement with the known backbone structure of natural gramicidin S in solution. By analyzing the anisotropic chemical shift of the 19F-labels in macroscopically oriented membrane samples, we determined the alignment of the peptide in the bilayer and described its temperature-dependent mobility. In the gel phase, the 19F-labelled gramicidin S is aligned symmetrically with respect to the membrane normal, i.e., with its cyclic beta-sheet backbone lying flat in the plane of the bilayer, which is fully consistent with its amphiphilic character. Upon raising the temperature to the liquid crystalline state, a considerable narrowing of the 19F-NMR chemical shift dispersion is observed, which is attributed the onset of global rotation of the peptide and further wobbling motions. This study demonstrates the potential of the 19F nucleus to describe suitably labelled polypeptides in membranes, requiring only little material and short NMR acquisition times. PMID- 11775739 TI - Rapid protein fold determination using secondary chemical shifts and cross hydrogen bond 15N-13C' scalar couplings (3hbJNC'). AB - The possibility of generating protein folds at the stage of backbone assignment using structural restraints derived from experimentally measured cross-hydrogen bond scalar couplings and secondary chemical shift information is investigated using as a test case the small alpha/beta protein chymotrypsin inhibitor 2. Dihedral angle restraints for the phi and psi angles of 32 out of 64 residues could be obtained from secondary chemical shift analysis with the TALOS program (Corneliscu et al., 1999a). This information was supplemented by 18 hydrogen-bond restraints derived from experimentally measured cross-hydrogen bond 3hbJNC' coupling constants. These experimental data were sufficient to generate structures that are as close as 1.0 A backbone rmsd from the crystal structure. The fold is, however, not uniquely defined and several solutions are generated that cannot be distinguished on the basis of violations or energetic considerations. Correct folds could be identified by combining clustering methods with knowledge-based potentials derived from structural databases. PMID- 11775740 TI - Joint refinement as a tool for thorough comparison between NMR and X-ray data and structures of HU protein. AB - Joint refinement, i.e., the simultaneous refinement of a structure against both nuclear magnetic resonance (NMR) spectroscopic and X-ray crystallographic data, was performed on the HU protein from Bacillus stearothermophilus (HUBst). The procedure was aimed at investigating the compatibility of the two data sets and at identifying conflicting information. Wherever important differences were found, such as peptide flips in the main-chain conformation, the data were further analyzed to find the cause. The NMR data showed some errors arising either from the manual interpretation of the spectra or from the incorrect account for spin diffusion. The most important artefact inherent to the X-ray data is the crystal packing of the molecules: the effects range from the limitation of the freedom of the flexible parts of the HUBst molecule to possibly one of the peptide flips. PMID- 11775741 TI - Amide proton temperature coefficients as hydrogen bond indicators in proteins. AB - Correlations between amide proton temperature coefficients (deltasigmaHN/deltaT) and hydrogen bonds were investigated for a data set of 793 amides derived from 14 proteins. For amide protons showing temperature gradients more positive than -4.6 ppb/K there is a hydrogen bond predictivity value exceeding 85%. It increases to over 93% for amides within the range between -4 and -1 ppb/K. Detailed analysis shows an inverse proportionality between amide proton temperature coefficients and hydrogen bond lengths. Furthermore, for hydrogen bonds of similar bond lengths, values of temperature gradients in alpha-helices are on average I ppb/K more negative than in beta-sheets. In consequence. a number of amide protons in alpha-helices involved in hydrogen bonds shorter than 2 A show deltasigmaHN/deltaT < -4.6 ppb/K. Due to longer hydrogen bonds, 90% of amides in 3(10) helices and 98% in beta-turns have temperature coefficients more positive than -4.6ppb/K. Ring current effect also significantly influences temperature coefficients of amide protons. In seven out of eight cases non-hydrogen bonded amides strongly deshielded by neighboring aromatic rings show temperature coefficients more positive than -2 ppb/K. In general, amide proton temperature gradients do not change with pH unless they correspond to conformational changes. Three examples of pH dependent equilibrium showing hydrogen bond formation at higher pH were found. In conclusion, amide proton temperature coefficients offer an attractive and simple way to confirm existence of hydrogen bonds in NMR determined structures. PMID- 11775742 TI - MUNIN: application of three-way decomposition to the analysis of heteronuclear NMR relaxation data. AB - MUNIN (Multidimensional NMR Spectra Interpretation), a recently introduced approach exploiting the mathematical concept of three-way decomposition, is proposed for separation and quantitative relaxation measurements of strongly overlapped resonances in sets of heteronuclear two-dimensional spectra that result from typical relaxation experiments. The approach is general and may also be applied to sets of two-dimensional spectra with arbitrary modulation along the third dimension (e.g., J-coupling, diffusion). Here, the method is applied for the analysis of 15N rotating frame relaxation data. PMID- 11775743 TI - Efficient identification of amino acid types for fast protein backbone assignments. AB - We describe a procedure that allows for very efficient identification of amino acid types in proteins by selective 15N-labeling. The usefulness of selective incorporation of 15N-labeled amino acids into proteins for the backbone assignment has been recognized for several years. However, widespread use of this method has been hindered by the need to purify each selectively labeled sample and by the relatively high cost of labeling with 15N-labeled amino acids. Here we demonstrate that purification of the selectively 15N-labeled samples is not necessary and that background-free HSQC spectra containing only the peaks of the overexpressed heterologous protein can be obtained in crude lysates from as little as 100 ml cultures, thus saving time and money. This method can be used for fast and automated backbone assignment of proteins. PMID- 11775744 TI - An easy way to include weak alignment constraints into NMR structure calculations. AB - We have recently shown that an energy penalty for the incorporation of residual tensorial constraints into molecular structure calculations can be formulated without the explicit knowledge of the Saupe orientation tensor (Moltke and Grzesiek. J. Biomol. NMR, 1999, 15, 77-82). Here we report the implementation of such an algorithm into the program X-PLOR. The new algorithm is easy to use and has good convergence properties. The algorithm is used for the structure refinement of the HIV-1 Nef protein using 252 dipolar coupling restraints. The approach is compared to the conventional penalty function with explicit knowledge of the orientation tensor's amplitude and rhombicity. No significant differences are found with respect to speed, Ramachandran core quality or coordinate precision. PMID- 11775746 TI - 1H, 15N and 13C assignments of the catalytic domain of E6-associated protein (E6AP). PMID- 11775745 TI - NMR structure of human fibronectin EDA. PMID- 11775748 TI - A place at the global policy table: the WHO global advisory group on nursing and midwifery. PMID- 11775749 TI - The stem cell research controversy. PMID- 11775747 TI - Letter to the editor: backbone 1H, 15N, and 13C resonance assignments of inhibitor-1--a protein inhibitor of protein phosphatase-1. PMID- 11775750 TI - Nursing is never dull, never routine. A conversation with Christine Hancock. PMID- 11775751 TI - ICN co-sponsors osteoporosis tour. PMID- 11775752 TI - Nurses always there for refugees in Angola. PMID- 11775753 TI - The capacity to care. PMID- 11775754 TI - Worldwide overview of critical care nursing organizations and their activities. AB - While critical care has been a specialty within nursing for almost 50 years, with many countries having professional organizations representing these nurses, it is only recently that the formation of an international society has been considered. A three-phased study was planned: the aim of the first phase was to identify critical care organizations worldwide; the aim of the second was to describe the characteristics of these organizations, including their issues and activities; and the aim of the third was to plan for an international society, if international support was evident. In the first phase, contacts in 44 countries were identified using a number of strategies. In the second phase, 24 (55%) countries responded to a survey about their organizations. Common issues for critical care nurses were identified, including concerns over staffing levels, working conditions, educational programme standards and wages. Critical care nursing organizations were generally favourable towards the notion of establishing a World Federation of their respective societies. Some of the important issues that will need to be addressed in the lead up to the formation of such a federation are now being considered. PMID- 11775755 TI - Reorganized structure and other proposals for the ICNP development. International Classification for Nursing Practice. AB - All of those who are engaged in the International Classification for Nursing Practice (ICNP) project are aware of the mistakes still being found in its classification. However, these are not recognized as faults, but rather as a challenge for better work and continuous efforts on its improvement. This article discusses proposed changes to the structure of the ICNP, according to the rules of building such 'tools', as well as new axes that can be added to make the classification beneficial across a broader spectrum of applications, not solely in electronic patient record-keeping and statistics. PMID- 11775756 TI - Compliance with hormone replacement therapy among Swedish women. AB - By means of a simple postal questionnaire, all women registered as hormone therapy patients (n = 241) at a gynaecological clinic were screened for reasons for receiving hormone therapy. They were also screened for their compliance in following the midwife's advice and information, as well as the gynaecologist's prescriptions. The majority of the women participating in this study contacted the clinic for climacteric symptoms. The time duration for using hormone therapy ranged from 1 month to 6 years. Those using a plaster or gel were asked why they should take progesterone pills. Forty per cent gave erroneous answers or did not know. Of these, 62% reported that they understood the oral information, whereas 60% reported that they understood the written information. Fifty-three per cent of the women stated that they would stop their hormone therapy if they did not feel well or increased in weight. New discoveries or information about benefits or risks were given by 22% as reasons affecting their decision. Compliance demands well-motivated and well-informed patients. The implication of the study result for practice is that there must be dialogue between the women and their midwife/ gynaecologist. It is important that the women feel they are receiving treatment which they have given their consent to, and that they feel and know that they are performing self-care. Midwives have recurrent contact with women during their life and have already established a relationship with them, which facilitates an individualized communication. PMID- 11775757 TI - High-risk sexual behaviours and genital infections during pregnancy. AB - This article describes the sexual behaviours of some pregnant women that contribute to vaginal and cervical infections, and describes their lack of awareness about the dangers associated with sexually transmitted infections during pregnancy. It presents a subanalysis of data from a principal epidemiological study of the association between preterm delivery and genital hygiene habits and sexual behaviour during pregnancy. One-hundred and nine postpartum women were questioned about high-risk sexual behaviours during their pregnancies, their partner's sexually transmitted disease status and their knowledge about the effect of sexually transmitted infections on their pregnancy. Global concerns about the prevalence, diagnosis and treatment of cervical and vaginal infection from sexually transmitted diseases are discussed. The dangers associated with high-risk sexual behaviours during pregnancy, and recommendations for clinicians, are included. PMID- 11775758 TI - Knowledge, attitudes and practices of nursing staff in a rural hospital of Cameroon: how much does the health care provider know about the human immunodeficiency virus/acquired immune deficiency syndrome? AB - Qualitative and quantitative approaches were used in a rural hospital of Cameroon to assess how much nursing personnel know about and practise in regard to human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and to determine health service factors that influence knowledge, attitudes and practices (KAP). Participants included 107 nursing and laboratory staff and 62 patients with AIDS. Self-administered questionnaires were used for nurses, and close-ended questionnaires were administered to patients with AIDS (as a verification tool for staff responses). Focus group discussions (FGD) held with nurse supervisors evaluated health service factors that influence KAP. Overall, 70.1% of the nurses who responded scored highly in the knowledge section compared to 50.5% in the attitude and practice section. There were several outstanding misconceptions and malpractices about HIV/AIDS. Knowledge, but not attitude, was significantly influenced by the grade of the staff (P< 0.001 and P = 0.17, respectively). Approximately 15% of 62 patients with AIDS indicated that they were attended to with signs of disgust and/or hatred. The major health service factors thought to influence KAP, confirmed by many in all the FGD, included: the lack of adequate information; the lack of commitment to alter attitudes and practices; the lack of in-service promotions; and the ongoing fear of becoming infected with the virus through caring for patients with AIDS. Low income also seemed to have an influence on KAP. Therefore, it is imperative that ongoing education programmes are provided for nurses to enable them to meet the needs of the increasing HIV prevalence in our community. Information, education and communication, and compliance with international working norms, remain essential tools in the control of HIV/AIDS spread in our hospital settings. PMID- 11775759 TI - The lie of primum non nocere. PMID- 11775760 TI - The new U.S. preventive services task force. PMID- 11775761 TI - Breaking bad news: the many roles of the family physician. PMID- 11775762 TI - Percutaneous interventions for lower extremity peripheral vascular disease. AB - Peripheral vascular disease of the lower extremities is an important cause of morbidity that affects up to 10 million people in the United States. The primary care physician can easily identify patients who are at risk for the disease with a questionnaire and a relatively simple test-the ankle brachial index. More than 70 percent of patients diagnosed with the disease remain stable or improve with conservative management. Those who do not improve may undergo contrast angiography or magnetic resonance angiography, which may be used in planning for surgery or percutaneous intervention. Surgical bypass is the gold standard for extensive vascular occlusive disease, but endovascular interventions, including percutaneous transluminal angioplasty and stent placement, are being used more frequently, particularly in patients with significant comorbid conditions. PMID- 11775763 TI - Breaking bad news. AB - Breaking bad news is one of a physician's most difficult duties, yet medical education typically offers little formal preparation for this daunting task. Without proper training, the discomfort and uncertainty associated with breaking bad news may lead physicians to emotionally disengage from patients. Numerous study results show that patients generally desire frank and empathetic disclosure of a terminal diagnosis or other bad news. Focused training in communication skills and techniques to facilitate breaking bad news has been demonstrated to improve patient satisfaction and physician comfort. Physicians can build on the following simple mnemonic, ABCDE, to provide hope and healing to patients receiving bad news: Advance preparation--arrange adequate time and privacy, confirm medical facts, review relevant clinical data, and emotionally prepare for the encounter. Building a therapeutic relationship-identify patient preferences regarding the disclosure of bad news. Communicating well-determine the patient's knowledge and understanding of the situation, proceed at the patient's pace, avoid medical jargon or euphemisms, allow for silence and tears, and answer questions. Dealing with patient and family reactions-assess and respond to emotional reactions and empathize with the patient. Encouraging/validating emotions--offer realistic hope based on the patient's goals and deal with your own needs. PMID- 11775764 TI - Neurotic excoriations. AB - Neurotic excoriations are self-inflicted skin lesions produced by repetitive scratching. Because there is no known physical problem of the skin, this is a physical manifestation of an emotional problem. The classic lesions are characterized by clean, linear erosions, scabs and scars that can be hypopigmented or hyperpigmented. The lesions are usually similar in size and shape, and are grouped on easily accessible and exposed body sites, such as extensor surfaces of the extremities, face and upper back. Psychotropic medications and appropriate counseling can be effective treatments. PMID- 11775765 TI - Office management of digital mucous cysts. AB - Digital mucous cysts are solitary, clear, or flesh-colored nodules that develop on the dorsal digits between the distal interphalangeal joint and the proximal nail fold. There are two types of digital mucous cysts: one type is associated with degenerative changes in the distal interphalangeal joint, and the second type is independent of the joint and arises from metabolic derangement of fibroblasts that produce large quantities of hyaluronic acid. The two types are clinically indistinguishable. The cysts can be asymptomatic, or they can cause pain, tenderness, or deformity of the nail. Aggressive surgical techniques to remove osteophytes from the joint can produce low recurrence rates. Other procedures to eliminate cysts, such as a simple surgical technique, cryosurgical destruction, or repeated needling, can be performed in an office setting. PMID- 11775766 TI - Newborn hearing screening: recommendations and rationale. PMID- 11775767 TI - PHS guidelines for management of occupational exposure to HBV, HCV and HIV: management of occupational blood exposures. PMID- 11775768 TI - Nonphysicians practicing medicine: a consumer safety issue. PMID- 11775769 TI - Biologic therapy for psoriasis: a brief history, II. AB - This article, the second in a 2-part series, will review interleukin 10 (IL-10) administration, the T-cell receptor mimic peptide, and CTLA4Ig. We also will review 4 of the most promising therapies currently being investigated for the treatment of psoriasis: infliximab, etanercept, efalizumab, and alefacept. PMID- 11775770 TI - Dermoscopy in the diagnosis of tinea nigra plantaris. AB - Tinea nigra is a relatively uncommon dermatiaceous fungal infection, usually caused by Phaeoannellomyces werneckii, that may mimic a melanocytic lesion. We describe the value of epiluminescent dermoscopy of tinea nigra plantaris compared with other common diagnostic tools and procedures available (clinical appearance, potassium hydroxide [KOH], culture, culture mount preparation, and biopsy). A case of tinea nigra plantaris was evaluated clinically, microscopically with KOH, and dermatoscopically. Dermatoscopic findings were evaluated according to the Stolz system. Dermoscopy, clinical presentation, and microscopy with KOH all confirmed the diagnosis, with dermoscopy being the fastest and simplest procedure. Dermoscopy is a useful clinical adjuntive tool in differentiating tinea nigra from a melanocytic lesion. PMID- 11775771 TI - Clinical review: thioureas and allergic contact dermatitis. AB - Thioureas are an uncommon underrecognized cause of allergic contact dermatitis (ACD). This article presents the findings in 3 individuals with ACD to thioureas and reviews the medical literature concerning thiourea-induced ACD. Thioureas are often the allergenic sources in ACD involving high-grade rubber products made of neoprene. Standard patch test series and rubber allergen patch test series usually do not contain thiourea allergens and will fail to diagnose these causes of ACD. Thioureas--most notably diethylthiourea, dibutylthiourea, and diphenylthiourea--should be considered in individuals with potential rubber allergy who fail to react to antigens in the standard allergen patch test tray. PMID- 11775772 TI - Imiquimod for plantar and periungual warts. AB - Plantar and periungual warts are notoriously difficult to eradicate. Two cases of nongenital warts in teenage girls are presented. Imiquimod was used in combination with cryotherapy for the periungual warts and with occlusion for the plantar warts. Both cases showed complete resolution and that imiquimod may be more effective on thicker keratinized (nongenital) skin when occluded or used in combination with cryotherapy. PMID- 11775773 TI - High frequency acoustic parameters of human and bovine articular cartilage following experimentally-induced matrix degradation. AB - Matrix degradation and proteoglycan loss in articular cartilag eare features of early osteoarthritis. To determine the effect of matrix degradation and proteoglycan loss on ultrasound propagation in cartilage, we used papain and interleukin-1alpha to degrade the matrix proteoglycans of human and bovine cartilage samples, respectively. There is also minor collagen alteration associated with these chemical degradation methods. We compared the speed of sound and frequency dependent attenuation (20-40 MHz) of control and experimental paired samples. We found that a loss of matrix proteoglycans and collagen disruption resulted in a 20-30% increase in the frequency dependent attenuation and a 2% decrease in the speed of sound in both human and bovine cartilage. We conclude that the frequency dependent attenuation and speed of sound in articular cartilage are sensitive to experimental modification of the matrix proteoglycans and collagen. These findings suggest that ultrasound can potentially be used to detect morphologic changes in articular cartilage associated with the progression of osteoarthritis. PMID- 11775774 TI - Scanning electric conductivity gradients with ultrasonically-induced Lorentz force. AB - The ions in a fluid element oscillating under the effect of a sound wave in the presence of a magnetic field are submitted to Lorentz force. This gives rise to a bulk current density proportional to the medium's electric conductivity. In the present study, the integrality of this interaction current was collected using a pair of plane electrodes located on opposite sides of the sample. A focused transducer produced ultrasound bursts of 10 micros duration, 500 kHz frequency and 1.5 MPa peak pressure. The magnetic field was created by a purpose-built 0.35 T permanent magnet. Wiener inverse filtering was used to retrieve the system response from the recorded waveforms. The final signal was shown to be proportional to the gradient of sigma/rho along ultrasound propagation axis. Electric conductivity, sigma, predominantly controls this parameter since mass density, rho, does not vary in great proportions in biological media. Rectangular blocks of Agar gel and a layered bacon sample were used as models of biological media. The signals obtained in gel blocks had a longitudinal spatial resolution better than 1 mm. The successive layers of the bacon sample were clearly resolved. The advantages of this new modality for tissue characterization include the permeability of body tissue to magnetic field and ultrasound, the harmlessness of the applied fields and the improved spatial resolution in the measurement of a tissue's electric conductivity distribution. PMID- 11775775 TI - Filter-based synthetic transmit and receive focusing. AB - Most diagnostic ultrasonic imaging systems perform fixed focusing on transmit and dynamic focusing on receive. Such systems suffer from image quality degradation at depths away from the transmit focal zone. Several dynamic transmit focusing techniques have been previously investigated. Among them, a filter-based, retrospective focusing technique was proposed to increase the length of the transmit focal zone. In this paper, the filter-based technique is extended from dynamic receive focusing to fixed receive focusing. It is shown that the filtering technique with fixed receive focusing can achieve an image quality similar to that of dynamic receive focusing with filtering. The performance of the proposed approach is verified using real ultrasound data. It is shown that the proposed approach with fixed receive focusing requires a longer filter than that with dynamic receive focusing. Nonetheless, system complexity is greatly reduced with synthetic transmit and receive focusing because the dynamic receive focusing circuit is no longer needed. PMID- 11775776 TI - Feasibility study of time-intensity-based blood flow measurements using deconvolution. AB - Ultrasonic contrast agents have been used to enhance the acoustic backscattered intensity of blood and to assist the assessment of blood flow parameters. One example is the time-intensity method based on the indicator-dilution theory. In this case, a mixing chamber model can be employed to describe the concentration of the contrast agent as a function of time. By measuring the time intensities at both the input and output of the blood mixing chamber, blood flow information can be obtained if proper deconvolution techniques are applied. Note that most deconvolution techniques assume a linear and time invariant (LTI) system for the mixing of the contrast agent with blood. In this paper, the hypothesis that a blood mixing chamber is an LTI system was tested. Several aspects were studied. One aspect was the linear relationship between the concentration of the contrast agent and the backscattered intensity. The other aspect was the dependence of the derived time constants on the concentration. The concept of an effective mixing volume was also introduced and evaluated. Finally, the input and the output time constants were measured and compared to theory under the LTI assumption. Extensive experiments were performed. Two in vitro flow models were constructed and two contrast agents were used. Results indicated that the LTI assumption does not hold and quantitative flow estimation is generally not possible. Nonetheless, the indicator-dilution theory can still be applied if only relative measurements of the flow rate are required. PMID- 11775777 TI - Economics and public health--reflections from the past and challenges for the future. PMID- 11775778 TI - Public health in Scandinavia--the case of Sweden. PMID- 11775779 TI - The new Swedish national public health policy. PMID- 11775780 TI - Being a psychiatric patient in the community--reclassified as the stigmatized "other". AB - AIMS: To explore the experiences of psychiatric patients living in six rural communities in Norway from a primary care perspective. METHODS: A "Knowledge workshop" (KW) was designed. It was a special kind of meeting between users of services for people with mental illness and service providers. The process and outcome were documented on flipcharts and audiotape and analysed by a qualitative method. RESULTS: A main statement was constructed in order to capture the essence of meaning in the 10 main themes identified in the analysis. The statement is mainly about the process and state of being reclassified as a stigmatized "other", with serious consequences for both self-esteem and public esteem. The consequences include isolation and loneliness, low self-esteem, no paid work, lack of money, discrimination, and harassment. Other consequences include altered behaviour from others, lack of necessary conditions for empowerment, and the danger of becoming visible as mentally ill. Attitudinal change is called for. CONCLUSIONS: Although the stigma of mental illness is a wellknown and much discussed fact, it has so far not really been included in the professional knowledge base. It is still practically absent from discussions of quality of care. In order for services to be relevant to people who need them, professionals can no longer ignore issues that are of major importance for users. Stigma must thus be included in the conceptual thinking about serving people with mental illness. The inclusion of stigma as an issue for quality of care could be a fruitful way forward. PMID- 11775781 TI - A comparative analysis of different methods for obtaining estimates of alcohol consumption in a Danish population survey. AB - AIMS: The aim of the present study was to compare different measures of alcohol consumption used in a Danish survey. METHODS: A stratified random sample was extracted from the Civil Registration System. From January 1997 to January 1998 approximately 8 telephone interviews were conducted every day, including Sundays and holidays, ending with a total of 3,050 interviews after 1 year. Two main approaches to measure alcohol consumption were used: the quantity-frequency and the recent occasion approaches; the latter is subdivided into previous week and previous day approaches. RESULTS: The overall estimated number of units (= 12 g of pure alcohol) per week was 6.8 (95% confidence intervals (CI): 6.5-7.1), 6.7 (95% CI: 6.4-7.1) and 8.5 (95% CI: 7.8-9.1) for the quantity-frequency, previous week and previous day approaches, respectively. A total of 50% of the men and 70% of the women did not drink alcohol the previous day. Among people classified as high consumers in the previous week and previous day approaches, less than 60% and 30%, respectively, were similarly classified in the quantity-frequency approach. CONCLUSION: There was agreement on the level of alcohol consumption between the quantity-frequency and previous week approaches, but higher estimates when using the previous day approach. The previous day approach varied more in relation to the interview day and season compared with the quantity-frequency approach and the previous week approach. The recent occasions approach showed some difficulties in classifying the individuals. If the alcohol consumption is included in a model as a risk indicator or a confounder, the quantity-frequency approach would be more preferable than the recent occasion approach. PMID- 11775782 TI - Sociodemographic predictors of self-rated health in patients with diabetes of short duration. AB - AIMS: To examine the impact of gender and socioeconomic factors on health-related quality of life (HRQoL) one year and eight years after diabetes diagnosis. METHODS: Two national incidence cohorts who contracted diabetes between the ages of 15 and 34 years (n=554) and matched control groups from the general population of Sweden (n=1,029) were surveyed. Data on HRQoL, diabetes treatment, marital status, education, social class, and employment were collected via a questionnaire mailed to the younger cohort (aged 16-35) one year after diagnosis and to the older cohort (aged 23-42) eight years after diagnosis. Response rates were 73% among people with diabetes and 68% among the controls. Multivariable linear regression models were used to analyse the impact of gender and socioeconomic factors on HRQoL in the diabetic and control groups. The dependent variable was the "general health perceptions" score of the SWED-QUAL instrument, which corresponds to the "global self-rated health" concept. RESULTS: A model including all the sociodemographic variables explained 6% of the variance in self rated health one year after diabetes diagnosis and 13% of the variance eight years after diagnosis. In the control groups, the level of explanation was 2-3%. Female gender was an independent predictor of poor self-rated health in the older diabetic cohort, but not in the younger cohort. CONCLUSIONS: Gender and socioeconomic factors were more closely associated with self-rated health eight years after diabetes diagnosis than one year after diagnosis, indicating early sociodemographic stratification in the health of the diabetic populations studied. PMID- 11775783 TI - Immunization against Haemophilus influenzae type b in Sweden--a study of the introduction process. AB - AIMS: To study the introduction of Haemophilus influenzae type b (Hib) vaccination in Sweden, and to identify factors promoting and inhibiting the process. METHODS: The introduction of general childhood vaccination against Hib in Sweden in 1992-93 was studied using the Cultural Historical Activity Theory as a theoretical framework. RESULTS: Five activity systems were found to be involved in the introduction process, the systems of vaccine production, government administration, news distribution, science, and disease prevention. The critical factors for introduction of the programme were found to be the vaccine product, conception of the disease, government economy and public decision-making. CONCLUSIONS: The results show that a broad range of non-biomedical aspects must be considered when a public health intervention such as a general vaccination programme is introduced. PMID- 11775784 TI - Intentional childhood injuries in Greece 1996-97--data from a population-based Emergency Department Injury Surveillance System (EDISS). AB - AIM: It has been gradually recognized that intentional injuries among children represent a largely hidden problem in modern societies. With the exception of mortality, population-based data from Greece have not been previously reported. To assess the magnitude and the characteristics of intentional injuries among children aged 0-14 years old, data from the population-based Emergency Department Injury Surveillance System (EDISS) database during the period 1996-97 were used. METHODS: EDISS relies on personal interviews with children and their escorts who contact the emergency departments of three hospitals. Two of these hospitals are district hospitals of the county of Magnesia and the island of Corfu, whereas the other is a university children's hospital that covers the Greater Athens area on alternative days. RESULTS: Among 46.807 children recorded in EDISS, 108 injuries (0.23%) were attributed to acts of violence. Among the 108 intentional injuries, only 11 were caused by firearms or other weapons and only 4 concerned infants. In comparison to unintentional home and leisure injuries, intentional childhood injuries increase significantly with age and they are more common among migrant children. They occur more frequently during late night and early morning hours, they are more serious, and they are more often multiple and concentrated on the head. CONCLUSIONS: In Greece. a problem of violence directed against children does exist. The actual magnitude of this problem is difficult to estimate, but its size appears to be smaller in comparison with that reported in other populations. PMID- 11775785 TI - "It was really nice to have someone"--lay people with musculoskeletal disorders request supportive relationships in rehabilitation. AB - AIMS: To explore the lay person's perspective on the rehabilitation process. METHODS: A total of 20 interviews were conducted with women and men who had recent or more distant experience of sickness absence with musculoskeletal diagnoses. Grounded theory was used, which includes an inductive approach and theoretical sampling. The interviews focused on the individuals' own stories and experiences of factors that promoted or hindered the rehabilitation process. RESULTS: The interviewees emphasized how and by whom they had been treated rather than what type of rehabilitation programmes they had attended. They focused on the importance of supportive relationships from the private. occupational, and health care arenas. The relationship with rehabilitation agents (professionals who implemented rehabilitation) was described as having either supportive or non supportive qualities. Based on the interviewees' descriptions, a model was developed on the socioemotional qualities of the rehabilitation agent. The most promoting factor in the rehabilitation process was to have a professional mentor that is a rehabilitation agent who combines a supportive approach with individually chosen rehabilitation measures and goals. CONCLUSIONS: The lay person's perspective gave additional knowledge regarding rehabilitation and recovery from musculoskeletal disorders. The socioemotional qualities of the rehabilitation agents were emphasized by the interviewees and a model regarding these qualities was developed. This model needs to be tested further. A clinical implication of the present study is the need for rehabilitation agents to develop their communication skills further. PMID- 11775786 TI - A model-based analysis of professional practices in suicide prevention. AB - AIMS: The purpose of this study was to investigate what suicide prevention means in terms of practical interventions. Another purpose was to assess the feasibility of a previously developed theoretical model for analysing suicide prevention (1-3). METHODS: The data consisted of plans for action provided by professionals from five fields (n = 173) (psychologists [n = 41], clergy [n=37], nurses [n=34], social workers [n=32], and physicians [n=29]) as responses to an inquiry within the National Suicide Prevention Project in Finland. The plans were operationally described and theoretically interpreted using the model. RESULTS: The analysis indicated that practice patterns were more or less similar irrespective of the focus of suicide prevention. Neither did clear sectoral or professional profiles of practice appear. Clinical topics, individually focused interventions and curative strategies constituted the main approach. Interventions focused mainly on risk factors, the priorities being life crises, acute risk of suicide, coping of survivors, and a suicide attempt. The bulk of the strategies were aimed at developing professional interventions and skills. CONCLUSIONS: The model proved to be a feasible tool for differentiating and theoretically interpreting suicide-prevention approaches. The paradigm adopted by the sectors was versatile and comprehensive: the activities were multifocused, all aims of prevention and locations of intervention were included, and a common set of interventions--a "multimethod approach"--was applied. The adoption of the idea of risk as well as of protective factors can be interpreted as reflecting a process theory of suicide development. PMID- 11775787 TI - The Danish National Birth Cohort--its background, structure and aim. AB - BACKGROUND: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. METHODS: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000. a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this. PMID- 11775788 TI - Contacts of general practitioners with illegal immigrants. AB - AIMS: Violence and economic hardship cause many people to go to industrialized countries, often without obtaining a residence permit. The aim of this study is to gain insight into the factors that determine the occurrence of contacts in primary health care with such illegal immigrants. METHODS: Data were analysed on contacts with illegal immigrants from a national survey among Dutch general practitioners (GPs) (n = 1,148; response: 62%). RESULTS: GPs reported that they have on average 0.74 patient contacts with an illegal immigrant per week (95% CI: 0.56-0.92). This probably includes some over-reporting. Contacts are more likely in practices and communities that comprise more non-Dutch-born people and more (patients with) typically urban health problems. Working experience and demography of the GP are not independently associated with the occurrence of contacts. CONCLUSIONS: Contacts of Dutch GPs with illegal immigrants mostly occur in the deprived areas of the big cities. PMID- 11775789 TI - Early gender differences in adolescent tobacco use--the experience of a Swedish cohort. AB - BACKGROUND: In Sweden, the prevalence of tobacco use in the youth population differs by product and gender, but there are no longitudinal studies of gender differences in the uptake of smoking and use of oral snuff (OS). METHODS: A prospective cohort study ongoing in the County of Stockholm, encompassing 3,019 children recruited in 1997 in the fifth grade of compulsory school, of whom 96% were followed-up in the sixth grade. RESULTS: At baseline, 22% of the boys and 15% of the girls had ever smoked, respectively 8% and 3% had ever used oral moist snuff. One year later, the overall smoking prevalence had markedly increased, as did the transition to more advanced stages of smoking, especially among girls. Among boys who at baseline had only used oral snuff, 41% had also smoked cigarettes at follow-up. Lack of a firm intention to abstain from tobacco use was strongly associated with onset of experimentation within one year, particularly among boys. CONCLUSIONS: Tobacco uptake in pre-adolescence differs between genders, with an earlier initiation among boys and a more rapid transition to regular smoking among girls. In most cases, experimentation with oral snuff among boys marks the transition to cigarette smoking. PMID- 11775790 TI - Avoidable deaths from cancer in the Nordic countries around the year 2000. PMID- 11775791 TI - Viral hemorrhagic septicemia virus alters turbot Scophthalmus maximus macrophage nitric oxide production. AB - The effect of viral hemorrhagic septicemia virus (VHSV) in vitro infection on the nitric oxide (NO) production by turbot Scophthalmus maximus kidney macrophages has been addressed in the past. Previously, we had determined that only a small fraction of turbot possess head kidney macrophages that respond to a single exposure of lipopolysaccharide (LPS) with NO production (LPS-responsive macrophages), whereas macrophage cultures from other individuals were not activated by LPS alone and needed a combination of stimuli to respond (LPS-non responsive macrophages). In the current work, we examined the effect of VHSV on NO production by macrophages characterized as LPS-responsive macrophages or LPS non-responsive macrophages. Combinations of LPS and tumor necrosis factor alpha (TNF-alpha) and macrophage-activating factor (MAF) were also used to stimulate the cells for NO production. The effect of VHSV on NO production depends on the response to LPS alone. When a low multiplicity of infection was used (1.78 x 10( 3)), the NO production in response to LPS in LPS-responsive macrophages was significantly decreased. However, LPS-non-responsive macrophage cultures produced NO when a combination of LPS and VHSV was used. In the case of a higher VHSV multiplicity of infection (1.78), no significant change was observed in LPS-non responsive animals. Combinations of LPS with TNF-alpha, LPS with MAF, and TNF alpha with MAF were used to induce NO production in LPS-non-responsive macrophages. In all these cases, VHSV suppressed NO production, although at a significant level only when a combination of TNF-alpha and MAF was used for the induction of NO. PMID- 11775792 TI - Infectious pancreatic necrosis virus infection in Atlantic salmon Salmo salar post-smolts affects the outcome of secondary infections with infectious salmon anaemia virus or Vibrio salmonicida. AB - Infectious pancreatic necrosis (IPN) virus (IPNV) infection in Atlantic salmon Salmo salar L. post-smolts and its influence on the outcome of secondary infections with infectious salmon anaemia (ISA) virus (ISAV) or Vibrio salmonicida were studied. The infections with ISAV or V salmonicida were performed both in a period of acute IPN and in the following IPNV carrier stage, 3 and 6 to 8 wk after experimental IPNV challenge, respectively. An IPNV carrier condition at low virus titre did not influence the mortality rates after secondary infections. Neither the ISAV infection nor the V. salmonicida infection in experimentally induced IPNV carriers resulted in mortalities different from those observed after challenge of IPNV-free fish. At higher IPNV titres in Atlantic salmon with acute IPN, the outcome of secondary infections was quite different from that observed in IPNV-free fish and in IPNV carriers. In 2 different experiments significantly more fish died when fish with acute IPN were infected with V salmonicida than when fish were infected with V salmonicida alone. Mortality also started earlier in the double-infected group than in the group challenged with V. salmonicida alone, 3 to 4 and 8 d after V salmonicida infection, respectively. Similar results were observed independent of whether mortalities due to IPN alone were registered in the experiments. When Atlantic salmon with acute IPN were infected with ISAV, significantly fewer fish died than when fish were infected with ISAV alone. The ongoing IPNV infection seemed to provide some protection against development of ISA. PMID- 11775793 TI - Strain variation, based on the hemagglutinin gene, in Norwegian ISA virus isolates collected from 1987 to 2001: indications of recombination. AB - Infectious salmon anemia (ISA) is caused by a virus that probably belongs to the Orthomyxoviridae and was first recorded in Norway in 1984. The disease has since spread along the Norwegian coast and has later been found in Canada, Scotland, the Faroe Islands, Chile, and the USA. This study presents sequence variation of the hemagglutinin gene from 37 ISA virus isolates, viz. one isolate from Scotland, one from Canada and 35 from Norway. The hemagglutinin gene contains a highly polymorphic region (HPR), which together with the rest of the gene sequence provides a good tool for studies of epizootics. The gene shows temporal and geographical sequence variation, where certain areas are dominated by distinct groups of isolates. Evidence of transmission of ISA virus isolates within and between regions is given. It is suggested that the hemagglutinin gene from different isolates may recombine. Possible recombination sites are found within the HPR and in the 5'-end flanking region close to the HPR. PMID- 11775794 TI - Effects of shrimp density on transmission of penaeid acute viremia in Penaeus japonicus by cannibalism and the waterborne route. AB - To investigate the effects of shrimp density on mortalities of Penaeus japonicus in experimental penaeid acute viremia (= white spot syndrome), shrimp injected intramuscularly with penaeid rod-shaped DNA virus (PRDV) were reared at different densities. In Expt 1, challenged (10(-6) dilution of a PRDV preparation) shrimp were reared collectively in a tank or individually in separate chamber units. A significant difference in cumulative mortalities was found between collectively (75.6%) and individually (1.2%) reared groups after 30 d. In Expt 2, effects of density on mortality were clearly shown when challenged (10(-5) dilution) shrimp were reared collectively in tanks at high (260 shrimp m(-2)), middle (135 shrimp m(-2)) and low densities (73 shrimp m(-2)). The cumulative mortalities for 14 d in the high, middle and low density groups were 72, 46 and 18%, respectively. In Expt 3, challenged (10(-5) dilution) shrimp were reared collectively in 3 tanks (Groups A, B and C) at the same high density (260 shrimp m(-2)): Group A, dead shrimp were immediately removed to avoid transmission of the pathogen through cannibalism and the waterborne route; Group B, dead shrimp were removed at scheduled times but were separated from living shrimp by a net partition to avoid cannibalism; and Group C, dead shrimp were removed twice a day at scheduled times. Resulting cumulative mortalities for 20 d in Groups A, B and C were 4, 24 and 64 %, respectively. These results show that the higher mortalities occur in P. japonicus reared at the higher densities in experimental PRDV infection, and this phenomenon is caused mainly by a higher opportunity of horizontal transmission of the virus through cannibalism and the waterborne route. PMID- 11775795 TI - The susceptibility of the giant freshwater prawn Macrobrachium rosenbergii to Lactococcus garvieae and its resistance under copper sulfate stress. AB - Addition of copper sulfate (0.1 to 0.4 mg l(-1)) to tryptic soy broth (TSB) had no effect on growth rate of the bacterial pathogen Lactococcus garvieae. Giant freshwater prawns Macrobrachium rosenbergii were injected with L. garvieae (4 x 10(6) colony-forming units [cfu] prawn(-1)) grown in TSB or TSB containing copper sulfate at 0.1, 0.2, 0.3 or 0.4 mg l(-1). After 48 h, the cumulative mortality was significantly (p < 0.05) higher for prawns exposed to L. garvieae grown in 0.4 mg l(-1) copper sulfate than at the lower concentrations examined. In other experiments, prawns were injected with TSB-grown L. garvieae (4 x 10(6) and 2 x 10(5) cfu prawn(-1)), then held in water containing copper sulfate. After 8 h the mortality of L. garvieae-exposed prawns held in water containing 0.4 mg l(-1) copper sulfate was significantly higher than prawns held in water containing 0.2 and 0.3 mg l(-1) copper sulfate. At the lower L. garvieae density, cumulative mortality of prawns increased directly with ambient copper sulfate concentrations in the range of 0.2 to 0.4 mg l(-1). All prawns survived a 168 h exposure to 0.1 mg l(-1) copper sulfate. Prawns exposed to different concentrations of copper sulfate were examined for hemocyte density, phenoloxidase activity and respiratory burst. No significant differences in hemocyte density were observed among treatments. In prawns following a 48 h exposure to 0.1 mg l(-1) copper sulfate, phenoloxidase activity was decreased, but respiratory burst was increased. In conclusion, copper sulfate increased the virulence of L. garvieae to M. rosenbergii and modulated its immune system. Copper sulfate at 0.1 mg l(-1) decreased susceptibility of M. rosenbergii to L garvieae infection, whereas at 0.2 mg l(-1) the susceptibility was increased. The generation of superoxide anion by M. rosenbergii exposed to copper sulfate at a concentration higher than 0.2 mg l(-1) was considered to be cytoxic. PMID- 11775796 TI - Impact of the copepod Mytilicola orientalis on the Pacific oyster Crassostrea gigas in Ireland. AB - Infections of a population of Crassostrea gigas by the copepod Mytilicola orientalis were examined at an oyster growing site at Dungarvan, County Waterford, Ireland. Twenty-one samples, each consisting of 20 to 30 oysters have been examined over 2 yr. Condition, sex, reproductive stage, length, weight, glycogen content and other parasite burdens of the oysters were examined in relation to the degree of infection of M. orientalis; 14.38% of oysters were infested. Mean abundance was 0.6 oyster(-1) The maximum number of copepods in an oyster was 20. M. orientalis had no effect on condition, growth, sex, stage or glycogen content of the oyster but correlated with shell burrowing by Polydora sp. PMID- 11775797 TI - Experimental infection of white spot syndrome virus in freshwater crayfish Pacifastacus leniusculus. AB - The signal freshwater crayfish Pacifastacus leniusculus was found to be susceptible to infection with white spot syndrome virus (WSSV). Histopathological observations of various tissues of virus-injected crayfish showed similar symptoms to those from WSSV-infected penaeid shrimp, but no appearance of white spots on the cuticle or reddish body colour were observed, although these are the prominent gross signs of white spot disease in shrimp. A gene probe for detecting WSSV was developed in order to detect the virus in affected cells and tissues using in situ hybridisation. Strong signals were observed in cells of virus injected crayfish, but not in control-injected crayfish. The number of granular haemocytes in virus-injected crayfish was significantly higher than in sham injected and non-injected crayfish from Days 5 to 8 (p < or = 0.05) and Days 3 to 8 (p < 0.01) post-injection, respectively. The proportion of granular haemocytes in virus-injected crayfish was also significantly higher than in sham-injected controls from Days 3 to 8 (p < 0.01). These results indicate that WSSV has a significant effect on the proportion of different haemocyte types in the freshwater crayfish. PMID- 11775798 TI - Distribution of viral haemorrhagic septicaemia virus in wild fish species of the North Sea, north east Atlantic Ocean and Irish Sea. AB - A surveillance programme was initiated on the occurrence and distribution of viral haemorrhagic septicaemia virus (VHSV) in wild marine fish. Six research cruises were undertaken in an 18 mo period during 1997 and 1998, covering the North Sea, the Atlantic waters off the north and west coasts of Scotland and the Irish Sea. A total of 19,293 fish were sampled from 23 different species including cod, haddock, Norway pout, herring and sprat. Individual fish lengths were recorded and the fish were checked for lesions, haemorrhaging and other signs of disease. Pools of organ samples were taken for virus assay. The majority of fish sampled did not display clinical signs indicative of viral haemorrhagic septicaemia. A small number of cod were found with skin lesions and haddock with skin haemorrhaging. Of the 2081 organ and skin sample pools collected, 21 tested positive for VHSV by tissue culture and enzyme-linked immunosorbent assay. Seventeen of the isolates originated from Norway pout Trisopterus esmarkii, one from cod Gadus morhua (skin lesion), one from herring Clupea harengus, one from whiting Merlangius merlangus, and one from a previously unreported host species, poor cod Trisopterus minutus. PMID- 11775799 TI - An outbreak of VHSV (viral hemorrhagic septicemia virus) infection in farmed Japanese flounder Paralichthys olivaceus in Japan. AB - A rhabdoviral disease occurred in farmed populations of market sized Japanese flounder (hirame) Paralichthys olivaceus in the Seto Inland Sea of Japan in 1996. The causative agent was identified as viral hemorrhagic septicemia virus (VHSV) based on morphological, immunological, and genetic analyses. Diseased fish that were artificially injected with a representative virus isolate showed the same pathological signs and high mortality as observed in the natural outbreak. This is the first report of an outbreak of VHSV infection in cultured fish in Japan. Clinical signs of diseased fish included dark body coloration, an expanded abdomen due to ascites, congested liver, splenomegaly, and a swollen kidney. Myocardial necrosis was most prominent and accompanied by inflammatory reactions. Necrotic lesions also occurred in the liver, spleen and hematopoietic tissue, and were accompanied by circulatory disturbances due to cardiac failure. Hemorrhagic lesions did not always appear in the lateral musculature. Transmission electron microscopy revealed many rhabdovirus particles and associated inclusion bodies containing nucleocapsids in the necrotized myocardium. The histopathological findings indicated that the necrotizing myocarditis could be considered a pathognomonic sign of VHSV infection in Japanese flounder. PMID- 11775800 TI - I want to see them grow up. PMID- 11775801 TI - Mother to child transmission (MTCT). What we know and the challenges ahead. PMID- 11775802 TI - A focus on women: treatment, parenting, violence and political advocacy. PMID- 11775803 TI - The faces of AIDS in Uganda: Mulago Hospital. PMID- 11775804 TI - Kampala. Call to action. PMID- 11775805 TI - Declaration of a focus on women. PMID- 11775806 TI - [Operational research in Chinese tuberculosis control work]. PMID- 11775807 TI - [Postoperative infection outbreak of M. chelonae subsp. abscessus]. AB - OBJECTIVE: To study the pathogen of postoperative infection outbreak in a hospital in Shenzhen. METHODS: According to the Laboratory Science Procedure of Diagnostic Bacteriology in Tuberculosis published by Chinese Antituberculosis Association, Bergey's Manual of Determinative Bacteriology (ninth edition), and the Clinical Bacteriology Examination & Development, 97 wound exudates were cultivated by the traditional bacteriologic method. The strains were identified with three standard strains of M. chelonae subsp. chelonae, M. chelonae subsp. abscessus and M. fortuitum as controls. RESULTS: 26 fast-acid positive and fast growth nontuberculous mycobacterium were isolated from 97 exudates, then 41 strains including other 15 strains which were collected from the hospital were identified as M. chelonae subsp. abscessus. CONCLUSION: The outbreak of the postoperative infection happened in the hospital was caused by M. chelonae subsp. abscessus. PMID- 11775808 TI - [Clinical analysis of 90 cases with endobronchial tuberculosis]. AB - OBJECTIVE: To explore the clinical features and early definite diagnosis of endobronchial tuberculosis(EBTB). METHODS: Clinical symptoms, chest X-ray/CT manifestations and fiberoptic bronchoscopic findings of 90 cases with EBTB were analyzed. RESULTS: Main symptoms were as follows: cough in 75 cases, fever in 27, haemoptysis in 24, pleural pain in 18, dyspnea in 11, weight loss in 7, etc. Signs of airway obstruction were rare, localized wheezing was found only in 2 cases. 7 cases in chest X-ray were normal, and only 2 cases in CT were indicative of EBTB. Bronchoscopic results showed exudative lesions in 38% of the cases, granulomatous lesions in 9%, cicatricial lesions in 26%, ulcerative lesions in 17%, and normal-like demonstrations in 11%. Positive results were found in 8 out of 50 by sputum acid-fast staining, 73 out of 86 by bronchoscopic brushing smears, and 17 out of 56 by bronchial biopsies. CONCLUSIONS: The clinical features of EBTB are non-specific, and EBTB can not be excluded only by normal chest X-ray findings. In contrast to CT, bronchoscopy plays an important role in definite diagnosis of the disease. When patients with slight fever of unknown origin or respiratory symptoms do not respond to general treatment, EBTB should be suspected and early fibereoptic bronchoscopy be performed. Fiberoptic bronchoscopic brushing examination for acid-fast bacillus and bronchial biopsy are beneficial to rapid and definite diagnosis of EBTB. PMID- 11775809 TI - [Diagnosis and treatment of pulmonary hamartoma]. AB - OBJECTIVE: To summarize the characteristics of pathogenesis, image, treatment and prognosis of pulmonary hamartoma. METHODS: 39 cases with hamartoma confirmed by pathology received surgical operation during 1971-1998 period. Their clinical data including symptoms, disease courses, image characteristics and surgery types were investigated. The prognostic results of 31 cases were collected by a follow up study. RESULTS: The average age of morbidity was 44 years old and the mean disease course of hamartoma was 13 months. 21 cases without symptoms were determinated by chance and 18 cases with some extent of cough, expectoration, fever, chest distress, and short of breath. The hamartomas of 21 cases were in right lung, 18 in the left. Image characteristics presented as popcom-shaped tumor with clear border and without satellite focus. 31 cases underwent enucleation, 4 wedge-shaped resection, 3 lobectomy and 1 pneumonectomy. No recurrence or malignant change was demonstrated by follow-up study. CONCLUSIONS: Pulmonary hamartoma is a kind of neoplasms with satisfactory prognosis. Intraluminal hamartoma should be differentiated from hilar lung cancer. Localized resection should be performed for the treatment of the disease. PMID- 11775810 TI - [Analysis of the clinical characteristics and the pathology of large cell lung cancer]. AB - OBJECTIVE: To study the clinical characteristics and the pathology of large cell lung cancer (LCLC). METHODS: Comparing the microscopic and immunohistochemical findings with clinical data by analyzing 54 cases of surgically treated LCLC from 1978 to 1997. RESULTS: There were 6 cases of clear cell carcinoma and one case of giant cell carcinoma in 54 cases. Male:female was 5:1(45/9). LCLC accounted for 1.28% of all surgically treated lung cancers. The average survival time was 23 months. The positive rate of P53 protein expression was 65%(13/20). The positive rate of PCNA staining was 100%(20/20). CONCLUSIONS: LCLC may be divided into squamous type, adenomatous type, neuroendocrine type and undifferentiated type. PMID- 11775811 TI - [Kinin generation in acute and chronic airway inflammation]. AB - OBJECTIVE: To investigate the kinin generation pathways in acute and chronic airway inflammation. METHODS: BALF from patients with acute, chronic airway inflammation and healthy controls were collected. Kinins, Plasma kallikrein, alpha 2-macroglobulin and toluenesulphonyl-arginine methyl ester esterase activity (TAME-ea) in BALF were studied. RESULTS: Kinins and TAME-ea values were significantly higher in the BALF of patients with acute and chronic airway inflammation than those in the controls, but there was no significant difference between acute and chronic groups; PK and alpha 2-M values were significantly higher in the acute group than the in chronic one. Gel filtration revealed the highest TAME-ea peak at about 800,000 in the acute group, corresponding with the first alpha 2-M peak, whereas at about 40,000 in chronic bronchitis. The inhibition test of the TAME-ea showed that the TAME-ea peak at 800,000 was mainly due to PK and the TAME-ea peak at 40,000 was mainly due to TK. CONCLUSIONS: The results indicated that in acute airway inflammation kinins seem to be mainly generated by PK, whereas in chronic inflammation kininogenases other than PK- such as TK--seem to be more important. PMID- 11775812 TI - [Linked marker analysis of bronchial asthma in China]. AB - OBJECTIVE: To study the clinical application value of genetic linkage analysis for bronchial asthma with two STRs-D5S436 and D5S658. METHODS: Polymorphism of the two STRs were amplified by polymerase chain reaction, and the alleles identification were performed with denaturing polyacrylamide gel electrophoresis and silver-staining techniques. RESULTS: In 92 unrelated Chinese individuals, 8 alleles and 22 phenotypes in D5S436, 9 alleles and 28 phenotypes in D5S658 were observed. The heterozygosities were 78% and 73% respectively. The polymorphism information contents (PIC) were 0.76 and 0.80 respectively. Linkage analysis showed linkage of asthma related phenotypes (including asthma) with D5S436 on chromosome 5q (lod = 2.490, theta = 0.1). CONCLUSIONS: D5S436 and D5S658 were good genetic markers. Linkage analysis demonstrates that locus on chromosome 5q31 33 maybe was linked to the development of asthma in Chinese population. PMID- 11775813 TI - [Changes of the activities of ET-1 in the serum and BALF of ILD patients and their clinical significance]. AB - OBJECTIVE: To evaluate the roles of the Endothelin-1 (ET-1) in pathogenesis of the patients with interstitial lung disease (ILD). METHODS: The ET-1 activities in the serum and BALF from 10 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects non-smokers were determined using the radio-immunoassay. RESULTS: In the activities of ET-1 in the serum and BALF in the patients with sarcoiosis (62 +/- 29 and 17.0 +/- 2.4) ng/L and in the IPF (77 +/- 71 and 10 +/- 3) ng/L. was higher than those in the normal control subjects (20 +/- 8 and 4.0 +/- 0.6) ng/L. The activities of ET-1 in serum was negative correlated with PaO2 (r = -0.538, P < 0.01). The level of ET-1 in the BALF of the patient was positive correlated with total cells in BALF (r = 0.649, P < 0.01). The levels of ET-1 in the BALF in the sarcoidosis was positive correlated with the percentage of lymphocyte (r = 0.712, P < 0.01) but in patients with IPF was positive correlated with the percentage of neutrophil (r = 0.813, P < 0.01). CONCLUSIONS: ET-1 might play an important role in pathogenic of the patients with sarcoidosis and IPF. The levels of ET-1 can act as the markers of activity of disease. PMID- 11775814 TI - [Effect of cigarette smoke extract on E-cadherin expression of airway epithelial cells]. AB - OBJECTIVE: To explore the possible mechanism of injury by smoking, and the effect of cigarette smoke extract (CSE) on E-cadherin (ECD) expression in airway epithelial cells (AEC) was observed. METHODS: Mouse trachea and pig AEC were cultured in vitro. After CSE exposure, the expression of ECD in AECs was evaluated using immunohistochemical stain and image analysis. RESULTS: ECD was distributed on the plasma membrane at the cell junctions of AECs. At 12th and 24th hour after CSE exposure, the ECD expression on membrane decreased, whereas the cytoplasmic expression increased (P < 0.01) as compared with the normal controls. The expression at 24th hour was higher than that at 12th hour (P < 0.01). CONCLUSIONS: CSE decreases the membranous expression of ECD in AECs, but increases the cytoplasmic expression. The change of ECD expression may mediate the airway epithelial injuries by smoking. PMID- 11775815 TI - [The study of E-cadherin expression on injury and repair of epithelium of respiratory tract in smoking mice]. AB - OBJECTIVE: To investigate effects of smoking on E-cadherin (E-cd) expression of injury and repair of respiratory tract epithelium by observation of dynamic expression of E-cd on epithelial cells of respiratory tract in smoking mice. METHODS: Immunohistochemistry SP technique was used to examine E-cd expression on epithelial cells of respiratory tract in smoking mice of different stages and dosages and the morphological changes observed by light and electron microscopy respectively. RESULTS: Four and twelve weeks after smoking, the E-cd expression in the epithelial cells was significantly down-regulated compared with the control group (P < 0.01). Morphologically, the intercellular junction was loose, and the epithelial cells were injured and proliferated on the same time. Eight weeks after smoking, however, the E-cd expression was not different from that of the control group (P > 0.05). CONCLUSIONS: Smoking is able to cause wavy change of the E-cd expression on the epithelial cells which may play an important role in the injury and repair of the epithelial cell of the respiratory tract. PMID- 11775817 TI - [Importance of scientific research design to improve the quality of clinical study]. PMID- 11775816 TI - [Clinical observation of oral appliances in the treatment of obstructive sleep apnea syndrome]. AB - OBJECTIVE: To explore the effect of treatment with the oral appliances on 36 cases with obstructive sleep apnea syndrome (OSAS). METHODS: The patients are requested to put on the proper oral appliances when sleeping. Polysomnography (PSG) are used to measure the apnea hypoventilation index(AHI), lowest SaO2 and longest apnea time before and after treatment. RESULTS: Having been Compared with the obtained data, the AHI decreased, the lowest SaO2 increased and the longest apnea duration shortened significantly (P < 0.05) in OSAS patients after oral appliance treatment. CONCLUSIONS: The oral appliances helped to widen the upper airway, stabilized the lower jaw bone on a forward position to make the tongue and the soft palate move forward, increased the effective amount of inhaled air while sleeping and improved sleeping quality. There fore, it is an effective method for the treatment of OSAS. PMID- 11775818 TI - [Evaluation of preventive studies of Chinese Journal of Tuberculosis and Respiratory Diseases 1978-1997]. AB - OBJECTIVE: To investigate the current situation of clinical trial about preventive research paper on respiratory diseases in China. To stress the design of the research, and to improve the quality of the studies. METHODS: All the preventive and treatment studies of Chinese Journal of Tuberculosis and Respiratory Diseases (1978-1997) were assessed according to evidence based medicine (EBM) standard. RESULTS: In the past 20 years, 394 preventive study papers were published, 41 were random control trial (RCT), 50 were clinical control trial (CCT), the total percentage of RCT and CCT was 23.1%, and quality problem also existed. CONCLUSIONS: The design of the study in the respiratory diseases is not rigorous, thus the accuracy of the result is greatly affected. Improving the design of the research and the statistics method is very important to improve the quality of the research. PMID- 11775819 TI - [Utility of nocturnal oximetry for case finding in patients with suspected sleep apnea syndrome]. AB - OBJECTIVE: Pulse oximeter is a useful screening device for SAS. We studied whether measurement of SaO2 could identify patients with SAS and evaluate the severity of SAS. METHODS: 174 snorers were assessed clinically and then underwent formal PSG and oximetry test at the same time. From the oximetry data, the percentage of time spent at SaO2 below 90% (SIT90%), waking SaO2(H SaO2%), the lowest SaO2(L SaO2%) during sleep, the mean SaO2(M SaO2%) and the number of oxygen desaturation > or = 4% per hour (DI4) were calculated. We also divided 100 cases among them into four groups by AHI, which were G0(AHI < 5), G1(AHI 5-19), G2(AHI 20-39), G3(AHI > or = 40), and evaluated whether the SIT90, ISaO2, MSaO2 and DI4 are different among the four groups. RESULTS: There was an statistically significant correlation (r = 0.91 P < 0.001) between DI4 and AHI. DI4 > or = 5 per hour identified patients with AHI > 5 with a sensitivity of 94%; DI4 > or = 15 per hour identified patients with AHI > 5 with a specificity of 98%, and for patients with AHI > or = 20, the sensitivity was 100%. The SIT90 and DI4 were significantly different among the four groups (P < 0.01). CONCLUSIONS: Oximetry with DI4 < 5 practically excludes clinically significant SAS, and DI4 > or = 15 identified almost all of them. SIT90 and DI4 could be used as parameters in evaluating the severity of SAS. PMID- 11775820 TI - [Cephalometric analysis of the craniofacial bony structures in patients with obstructive sleep apnea]. AB - OBJECTIVE: To explore the craniofacial bony structure abnormalities and their possible contributions to the apneic severity in patients with obstructive sleep apnea (OSA). METHODS: One-night polysomnographic examination and a lateral cephalogram were performed in 102 male OSA patients and 37 healthy men. Sixteen variables representing craniofacial angle, distances and areas were measured by a computer software (NIH Image). RESULTS: Compared with normal subjects, OSA patients presented with: a shortened cranial base (71 +/- 4) mm: (74 +/- 3) mm, (P < 0.001), maxillum (52 +/- 5) mm: (55 +/- 4) mm, (P < 0.01), mandible (74 +/- 5) mm: (77 +/- 6) mm, (P < 0.05) and bony nasopharygeal airway dimensions, a more inferiorly and anteriorly placed hyoid bone, and retrognathia deformity. Multiple stepwise regression analysis disclosed that maxilla deficiency, retrognathia and hyoid bone misposition were important contributing factors to the apneic severity (R2 = 0.447, F = 15.471, P < 0.0001). CONCLUSIONS: OSA patients had certain craniofacial bony structure defects and cephalometric analysis of these defects is useful both in the investigation of the pathogenesis and the selection of an optimel treatment modality for each OSA patients. PMID- 11775821 TI - [Clinical value of nocturnal SaO2 mornitoring in patients with overlap syndrome at high altitude]. AB - OBJECTIVE: To study the nocturnal dynamic change of SaO2 in patients with overlap syndrome at high altitude, and to evaluate the value and significance of oxygen desaturation in assessing disease severity by means of polysomnography. METHODS: 13 patients with COPD and 12 with overlap syndrome were conducted nocturnal sleep, respiratory and dynamic SaO2 mornitoring. RESULTS: AHIs in the both groups were 3.7 +/- 1.3 and 35.7 +/- 12.9 respectively, and there was a significant difference between these two groups (P < 0.001). There were significant difference between these two groups in ISaO2, MSaO2, HSaO2, SIT85 and DI4(P < 0.005-0.001). There was a liner correlation between AHI and DI4. CONCLUSIONS: In patients with COPD, a suitable oxygen desaturation index has important clinical value on the preliminary selection and accurate diagnosis of SAS. PMID- 11775822 TI - [The relationship between sleep related breathing disorders and stroke]. AB - OBJECTIVE: To study the relationship between sleep related breathing disorder(SRBD) and cerebrovascular diseases (CVD). METHODS: Polysomnographic studies on 43 cases of CVD were performed and 43 sex-, age-, body mass index- compatible cases without CVD used as controls. RESULTS: The incidence of SRBD (mostly the obstructive one) was much more in CVD patients and both the obstructive and central apnea/hypopnea indices, deoxygenation indices were bigger and deoxygenation time were longer while the mean and lowest oxygen saturation were lower in CVD group than those in the controls (all P < 0.05). The blood pressure before sleep, after awakening and the mean BP during sleep were also higher in the CVD patients. In CVD group, the incidence of hypertension was also much higher in SRBD patients than that in non-SRBD ones (P < 0.01). SRBD was dangerous for CVD as OR value was 6.28. CONCLUSIONS: SRBD may be one important risk factor for CVD. An vicious circle might be formed between stroke and SRBD which inflences the outcome of stroke. PMID- 11775823 TI - [Comparison of AutoSet with polysomnography in the diagnosis of sleep apnea syndrome]. AB - OBJECTIVE: To evaluate the validation of the AutoSet system in the diagnosis of sleep apnea syndrome(SAS). METHODS: One hundred and twenty patients were studied simultaneously performed both with the AutoSet and the polysomnography(PSG). The apnea index(AI) and apneas + hypopneas index (AHI) were compared between the two methods by Bland and Altmen method. RESULTS: A significant correlation was found between the AHI assessed by the AutoSet and by the PSG (r = 0.92, P < 0.001). The respiratory irregularity index (RII) of the AutoSet was well correlated with the arousal index (Ai) from the PSG (r = 0.72, P < 0.001). The sensitivity and specificity of the AutoSet in diagnosing sleep apnea were 94% and 80% for AHI > or = 5/hour, 92% and 85% for AHI > or = 10/hour, 91% and 92% for AHI > or = 15/hour, 91% and 91% for AHI > or = 20/hour. CONCLUSIONS: The AutoSet system is a sensitive and valuable tool for identifying patients with sleep apnea and can make a diagnosis of sleep apnea for these patients with AHI > or = 30/hour, but has some limits especially for mild to moderate sleep apnea. PMID- 11775824 TI - [Diagnosis and treatment of primary small vessel vasculitis with involvement of lungs]. AB - OBJECTIVE: To investigate the clinical characteristics of primary small vessel vasculitis with involvement of lungs. METHODS: 13 cases of primary small vessel vasculitis with involvement of lungs from 1993 to 1998 were analyzed retrospectively. RESULTS: Among 13 cases 7 were microscopic polyangiitis (MPA) and 6 were Wegener granulomatosis (WG). The ages of onset were from 17 to 68 years old with average age 48.8 years old. 69%(9/13) were ANCA positive, among them 100%(7/7) MPA were ANCA positive (6/7 were P-ANCA positive, 1/7 was C-ANCA positive), while 33%(2/6) WG were ANCA positive (one case of P-ANCA and another case of C-ANCA was positive respectively). The major symptoms of respiratory system included hemoptasis 69% (9/13), dyspnea 23%(3/13), dry cough 15%(2/13) and chest pain 15%(2/13). The chest x-rays showed multiple patchy shadows in both lungs were mainly found in MPA (3/7) and single or multiple masses or nodular shadows were mainly found in WG (5/6) with or without cavity formation. The appearance of lungs in MPA 71% (5/7) had been explained as "pulmonary infection" and that of WG had been explained as "primary lung cancer or metastatic carcinoma". Symptoms of respiratory system might occur before (3/5) or after (2/5) occurrence of acute renal failure. The treatments with corticosteroid and CTX were effective in these cases, in particularly, pulmonary lesions improved obviously. CONCLUSIONS: It is very difficult to make diagnosis of primary small vessel vasculitis with involvement of lungs and this should be paid more attention. ANCA detection is very useful in diagnosis of MPA. Corticosteroid and CTX are most effective in treating these diseases. PMID- 11775825 TI - [The effect of cyclooxygenase-2 inhibitor on acute lung injury]. AB - OBJECTIVE: To investigate changes of cyclooxygenase-2 (COX-2) mRNA expression and intervention effect of selective cyclooxygenase-2 inhibitor Meloxicam on acute lung injury (ALI). METHODS: We measured COX-2 mRNA expression by reverse transcription polymerase chain reaction in rat lung with ALI induced by lipopolysaccharide, and observed changes of prostaglandins (PGs), PaO2 and histopathology. RESULTS: Resting rat lung expressed a little COX-2 mRNA; expression of cyclooxygenase-2 mRNA was up-regulated significantly in the lung after rats were injured by LPS. Selective COX-2 inhibitor Meloxicam alleviated histopathologic damage in the lung, inhibited production of PGs and attenuated PaO2 decline. CONCLUSIONS: COX-2 is a main isoform responsible for enhancing PGs production during ALI. Meloxicam can inhibit activity of COX-2 and may be useful in the treatment of ALI. PMID- 11775826 TI - [A series of clinical study on netilmicin]. AB - OBJECTIVE: To evaluate the clinical effects, pharmacokinetics, post-antibiotic effect (PAE) and toxicity of netilmicin as a single daily dose in the treatment of lower respiratory tract infection. METHODS: 48 cases were divided into 3 groups: In the first group, Netilmicin(6 mg.kg-1.d-1) was administered in a single daily dose; in the second group, netilmicin (200 mg/d) was combined with cefazolin (3 g, Q12 h); and in the third control group, the combination of cefazolin and Amikacin was used. Pharmacokinetics were studied in 7 patients using the TDX system, and PAE induced by Netilmicin was determined by the Avantage microbiologic system. Clinical symptoms, laboratory studies, chest X rays, and side effects were observed. RESULTS: The overall clinical effects of the first group were better than those of the third group. The mean serum concentration of netilmicin was 27.23 mg/L, the valley serum concentration was 0.23 mg/L, T1/2 beta was 5.059 h, AUC was 70 micrograms.h-1.ml-1.netilmicin at concentrations 0.5, 1.0 and 4 times the MIC showed different degrees of PAE against 4 strains of bacterium. Nephrotoxicity and ototoxicity were not found in the treatment group. CONCLUSIONS: Netilmicin in a single daily dose resulted in a high peak serum concentration and big AUC. As a concentration-dependent bactericidal agent, netilmicin showed a longer PAE and better therapeutic effects. PMID- 11775827 TI - [Characteristics and criteria for bronchial responsiveness measurement in cough variant asthma]. AB - OBJECTIVE: To investigate the value of sGaw in the differentiation of CVA from COPD. METHODS: MEFV, airway resistance(Raw) and bronchial responsiveness were measured in 30 cases with CVA, 133 cases with typical bronchial asthma(BA) and 37 cases with COPD. RESULTS: (1) The expiratory-flow parameters (PEF, MMEF, FEV1/FVC) in MEFV curve in remission period of CVA were largely normal, but most patients with CVA (67%) have increased Raw and decreased sGaw, characteristics similar with typical bronchial asthma (BA). (2) If PC35sGaw < 8 g/L was set as the positive limit, 100% of CVA and BA patients showed bronchial hyperresponsiveness(BHR), the average positive MCH concentration being about 1.0 g/L. 5 cases with COPD (13.5%) also showed BHR, but the average MCH concentration was 5.24 g/L. (3) If PC35sGaw < 4 g/L was set as the positive limit for the diagnosis of CVA, the sensitivity was 96.7%, specificity 97.3%, confidence limit 99%. (4) A equation for PC35sGaw was deduced, and its calculation values showed the same results with the ones from diagrammatization. CONCLUSIONS: sGaw is a sensitive index for the measurement of bronchial responsiveness, and it is useful in the differentiation of CVA from COPD. It is suggested that PC35sGaw < 8 g/L be regarded as bronchial hyperresponsiveness, and PC35sGaw < 4 g/L as candidate for CVA. PMID- 11775828 TI - [Surveillance of primary resistance in 481 cases of pulmonary tuberculosis]. AB - OBJECTIVE: To understand the primary resistance of Mycobacterium tuberculosis in Henan province, and to make scientific prophylactic and treatment strategies. METHODS: Drug resistance surveillance (DRS) was implemented in Henan province according to WHO/IUATLD Guidelines for Surveillance of Drug Resistance in Tuberculosis(1994), and proportional method was used to detect primary resistance in 481 new cases of bacillus-positive pulmonary tuberculosis without history of anti-tuberculosis drug use. RESULTS: The primary drug resistance(PDR) rates were 22.7%, 15.8%, 22.7% and 7.7% for INH, RFP, SM and EMB, respectively. The primary multi-drug resistance (MDR) rates were 2.3%, 5.0%, 0.4% and 5.4% for HR, HRS, HRE and HRSE, respectively. CONCLUSIONS: The results show that the problem of primary resistance of Mycobacterium tuberculosis is serious in Henan province, and uniform management of anti-tuberculosis drugs and implementation of DOTs are needed. PMID- 11775829 TI - Stimulatory activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors. AB - OBJECTIVE: To study the activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors on cAMP production and inward calcium currents (Ica) in guinea pig ventricular myocytes. A comparison was also made with those of a muscarinic receptor agonist. METHODS: cAMP content was determined by radioimmunoassay and the Ica in guinea pig single ventricular cells were recorded by the whole-cell patch clamp technique. RESULTS: Both the muscarinic receptor agonist, carbachol (Carb 10 mumol/L), and anti-peptide antibodies (Abs 100 nmol/L) could decrease basal cAMP levels (by 46.9% +/- 4.2% and 60.2% +/- 4.6%, respectively) and basal Ica. Both Carb (10 mumol/L) and Abs (100 nmol/L) could also inhibit the isoprenaline-induced (Iso 0.8 mumol/L) increases in cAMP production (from 108.2 +/- 7.0 to 88.4 +/- 7.2 pmol/mg.protein/min for Carb and 88.6 +/- 5.1 pmol/mg.protein/min for Abs, respectively) and the increases in Ica. The muscarinic receptor antagonist atropine (Atr) was able to prevent these effects of Carb and Abs. CONCLUSIONS: Anti-peptide antibodies against an epitope located in the second extracellular loop of human M2 muscarinic receptors, similar to muscarinic receptor agonist, could decrease the basal Ica and beta-receptor agonist stimulated increase of Ica by decreasing the basal and beta-receptor agonist stimulated increase of cAMP production, and therefore could have an effect on their target receptor. These results further suggest that autoimmunity may participate in the pathogenesis of human cardiomyopathy and the second extracellular loop of human M2 muscarinic receptor could be the main immunodominant region. PMID- 11775830 TI - Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis. AB - OBJECTIVES: To study mitogen-activated protein kinase (MAPKs) activation in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL-1 beta, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs. METHODS: Primary cultures of RA FLS were used. Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL-1 beta at various doses, and over different periods. Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL 1 beta. RESULTS: IL-1 beta transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK2, JNK2 and P38) in RA FLS. There was no obvious difference in MAPKs activation among different doses of IL-1 beta (1 IU/ml, 10 IU/ml, 100 IU/ml), but the peak activation of ERK2, JNK2 and P38 took place at 5 min, 15 min and 1 min, respectively, after stimulation with IL-1 beta. The activation of ERK2 was inhibited by genistein, but the inhibitory role on that of JNK and P38 was relatively weak. CONCLUSIONS: During signal transduction of IL-1 beta in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members. PTK had a role in the activation of ERK, but had weak effects on that of JNK and P38. PMID- 11775831 TI - The relationship between Th1/Th2-type cells and disease activity in patients with systemic lupus erythematosus. AB - OBJECTIVE: To investigate the imbalance of Th1/Th2-type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity. METHODS: Intracellular cytokines were determined by flow-cytometry following whole-blood culture. RESULTS: Patients with systemic lupus erythematosus disease activity index (SLEDAI) > 10 had statistically significantly fewer CD4+ or CD8+ T cells producing IFN-gamma than patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.01, P < 0.01 or P < 0.05, respectively). Patients with SLEDAI > 10 also had decreased ratio of IFN-gamma/IL-4 positive CD4+ or CD8+ T cells, compared with patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.05). The decreased Th1 or Tc1 cells and the ratios of IFN-gamma: IL-4 positive CD4+ T-cells were significantly correlated with disease activity (P < 0.05). CONCLUSION: SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines. The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity. PMID- 11775832 TI - Biological function of a novel gene overexpressed in human hepatocellular carcinoma. AB - OBJECTIVE: To clone the full-length of a differentially expressed cDNA fragment, LC27, and study its biological function tentatively. METHODS: Northern blot was used to analyze the expression pattern of LC27 in hepatocellular carcinoma, matched nontumor liver tissues, fetal liver and normal adult liver tissues, as well as BEL-7402 hepatocellular carcinoma cell line ESTs splicing and 5' rapid amplification of cDNA ends (5' RACE) were used to clone the full-length of LC27 cDNA. An antisense oligodeoxynucleotide approach was used to investigate the biological role of the gene in the proliferation of BEL-7402 cells. RESULTS: A 2186 bp novel cDNA with an open reading frame encoding a 283 amino acid protein was cloned. Analysis of the deduced amino acid sequence indicated that it is 38% (88/229) identical to human Golgi 4-transmembrane spanning transporter MTP. The gene and the encoded protein was termed hepatocellular carcinoma overexpressed transmembrane protein (hotp) and HOTP, respectively. Hotp mRNA was almost undetectable in normal adult liver and fetal liver tissues. However, it was significantly up-regulated in hepatocellular carcinoma and some matched nontumor liver tissues, as well as BEL-7402 cells. The proliferation of BEL-7402 cells was suppressed by an antisense oligodeoxynucleotide against hotp mRNA at a concentration of 50 micrograms/ml. CONCLUSION: HOTP may be an integral membrane transporter protein. The overexpression of the gene in hepatocellular carcinoma may play an important role in hepatocarcinogenesis and disease progression. PMID- 11775833 TI - Change of apoptotic status in the human colorectal adenoma-carcinoma sequences and its correlation with carcinogenesis and prognosis. AB - OBJECTIVE: To assess apoptotic status during the development of colorectal cancer and its prognostic value. METHODS: The apoptotic frequency of 168 fresh adenocarcinoma specimens and primary cultured cells at 2, 12, 24 and 48 hours (9 normal mucosa, 4 adenomas and 9 adenocarcinomas) were measured by flow cytometry (FCM). Apoptotic indices (AI) in situ for 25 adenomas and 77 adenocarcinomas were visualized by TdT-mediated dUTP nick end labeling (TUNEL), Ki-s5 labeling indices (KI), bcl-2, bax, waf1 and p53 were immunostained with ABC method. RESULTS: The culture-related apoptosis at 24-48 hours in vitro was obviously decreased in cultured tumor cells when compared with mucosa cells. Spontaneous apoptosis in situ occurred more frequently in tumor with aneuploid type at late stage. There was positive relationship between apoptosis and proliferative activity, determined by both TUNEL and FCM methods. The well-differentiated or early stage lesions with intensive bcl-2/bax expression were significantly more likely to have low AI. p53 accumulation and waf1 depression were mainly related to KI, whereas bax and waf1 overexpression led to a comparatively higher AI/KI ratio. bcl-2 and KI were found to be independent risk factors. CONCLUSIONS: The data suggest that the depressed susceptibility to inductive apoptosis may contribute to the initial phase of tumorigenesis, and spontaneous apoptosis in vivo may serve as a marker of tumor progression. The bcl-2 and KI may be valuable in predicting prognosis in colorectal cancer. PMID- 11775834 TI - Molecular and immunohistochemical study of the inactivation of the p16 gene in primary hepatocellular carcinoma. AB - OBJECTIVE: To determine whether p16 gene is involved in the genesis of primary hepatocellular carcinoma (HCC). METHODS: Twenty-five HCC tumor samples with corresponding non-tumor liver tissue specimens were examined for p16 gene alterations. The identification of deletion of exon 1 and exon 2 in p16 gene was performed using comparative multiplex polymerase chain reaction (PCR) analysis. The point mutation of exon 2 in p16 gene was investigated by single strand conformational polymorphism (SSCP) analysis, and the status of p16 gene methylation was screened using a PCR based methylation analysis. 35 parafin embedded specimens of HCC with corresponding non-tumor liver tissues, including the 25 cases described above for screening p16 gene alterations, were investigated for p16 protein expression using immunohistochemical analysis. RESULTS: Among 25 cases, 2 homozygous deletions and 1 hemizygous deletion were found in HCC samples. No point mutation was identified in the remaining 22 tumor samples without p16 gene deletions. Hypermethylation was detected in 24% (6/25) of tumor samples. However, the corresponding non-tumor liver tissue specimens were always unmethylated at the p16 locus. Loss of p16 protein expression occurred in 16 of 35 (45.7%) tumor samples, and all the non-tumor liver tissue specimens showed positive p16 staining. For the 25 cases examined for p16 gene alterations, the loss of p16 protein expression was observed in all tumors with p16 gene alterations and also in 3 tumors without p16 gene alterations. CONCLUSION: Inactivation of the p16 gene may play an important role in the genesis of primary hepatocellular carcinoma. PMID- 11775835 TI - Isolation of genes related to blood glucose-control in rat skeletal muscle. AB - OBJECTIVE: To isolate genes related to blood glucose-control using Sprague Dawley (SD) rat skeletal muscle. METHODS: Differential gene expression between glucose stimulated and non-glucose stimulated SD rat skeletal muscle was obtained by the differential display (DD) method, Slot blotting hybridization and Northern blot hybridization. RESULTS: Several new genes that are differentially expressed in glucose stimulated and non-glucose stimulated SD rat skeletal muscle were isolated. 74 were verified by slot analysis from 181 gene tags isolated. Of them, 33 were cloned and sequenced, and homologous analysis and application for GenBank Access Number were carried out. 21 expressed sequence tag (EST) representing novel genes was confirmed by Northern blot analysis. A total of 9 novel genes showed significant differential expression patterns. CONCLUSIONS: Using improvements and modifications of the differential display technique, a labor- and cost-saving route was used to identify new genes related to blood glucose control. We investigated differentially expressed genes at the whole body level instead of the culture cell level, to ensure experimental results closer to the normal physiological state. This technique may be valid in wide-spread application to other related research. PMID- 11775836 TI - Impact of RT-PCR monitoring on the long-term survival in acute promyelocytic leukemia. AB - OBJECTIVE: To evaluate the impact of kinetics of molecular remission via retro transcriptase polymerase chain reaction (RT-PCR) assay on the long-term survival in patients with acute promyelocytic leukemia (APL). METHODS: Seventy patients with newly-diagnosed APL in remission were involved in this study. Monitoring of minimal residual disease (MRD) was performed regularly by RT-PCR assay for PML RAR alpha during consolidation. RESULTS: A 5-year relapse-free survival (RFS) and overall-survival (OS) were estimated as 46.8% +/- 8.4% and 69.9% +/- 9.4% for the whole group. Fifty-two (74.3%) patients got negative RT-PCR result at least once. Serial monitoring of RT-PCR was available in 38 cases and 24 (63.2%) patients presented with persistent negative PCR results. The achievement and continuous negative RT-PCR result was significantly related to the RFS. CONCLUSIONS: Achievement of negative RT-PCR in remission is associated with favorable RFS and OS. Continuous negative RT-PCR results are associated with long-term relapse-free survival and may be considered as potentially curative. RT-PCR assay for detection of MRD should be performed regularly during post-remission period as an important prognostic factor. PMID- 11775837 TI - The effects of glucose, insulin and oxidized low density lipoprotein on apoptosis in vascular endothelial cells. AB - OBJECTIVE: To study the effects of high concentrations of glucose, insulin and oxidized low density lipoprotein (ox-LDL) on apoptosis in cultured bovine aortic endothelial cells (ECs). METHODS: For qualitative determination of EC apoptosis, acridine orange (AO)/ethidium bromide (EB) staining and DNA agarose gels electrophoresis were used. Cellular DNA fragmentation ELISA measured apoptosis by quantitating the fragmentation of 5-bromo-2'-deoxyuridine-labeled DNA. RESULTS: High concentrations of glucose (20 mmol/L, 40 mmol/L), insulin (3000 microU/ml) and ox-LDL (50 micrograms/ml, 100 micrograms/ml) induced concentration- and time dependent apoptosis in ECs. They had a synergetic effect on EC apoptosis. The combined effect of high concentration of glucose, insulin and ox-LDL was greater than any two of them; the effect of two was greater than one alone. Low concentration of insulin (30 microU/ml) decreased apoptosis in ECs induced by high concentrations of glucose (40 mmol/L), but no similar effect occurred with ox-LDL (100 micrograms/ml). CONCLUSION: High ambient glucose, insulin and ox-LDL can induce excessive apoptosis in cultured ECs, and low ambient insulin can prevent EC apoptosis. Excessive EC apoptosis induced by the separate or synergetic effect of hyperglycemia, hyperinsulinemia and hyperlipidemia may be one of the reasons for loss of endothelial integrity, dysfunction of the vascular endothelium and increased plasma membrane permeability, which are all involved in the development of diabetic macrovascular complications. PMID- 11775838 TI - Effect of IFN-gamma, IL-4 on proliferation and synthesis of hyaluronic acid and collagen in cultured human retroorbital fibroblasts in vitro. AB - OBJECTIVE: To investigate the cellular immune mechanism of thyroid associated ophthalmopathy (TAO) and provide a basis for treating TAO with cytokine or anti cytokine agents, we determined whether interferon (IFN)-gamma and interleukin (IL)-4, representative cytokines of Th1 and Th2 cells, may have some effect on the development and progression of TAO. METHOD: Retroorbital fibroblasts (RF) proliferation and the synthesis of hyaluronic acid (HA) and type IV collagen were measured with liquid scintillation and radioimmunoassay. RESULTS: IFN-gamma stimulated RF proliferation and HA synthesis and had a significant inhibitory effect on type IV collagen synthesis. IL-4 stimulated proliferation and type IV collagen synthesis in RF and had inhibitory effect on HA synthesis. When IFN gamma (100 U/ml) and IL-4 (1 microgram/L) were incubated together with RF, they antagonized their respective stimulatory or inhibitory effect on the proliferation and synthesis of HA and type IV collagen. Thyrotropin (TSH) stimulated RF proliferation and type IV collagen synthesis in a dose-dependent manner, while only at high dose (100 U/L and 200 U/L), stimulated RF to synthesize HA. CONCLUSIONS: IFN-gamma, a representative cytokine of Th1 cells, is responsible for the inflammatory process of TAO; whereas IL-4, a representative cytokine of Th2 cells, has some effect on the repair process. IL-4 could antagonize the inflammatory effect of IFN-gamma on RF. TSH may have aggravating effect on the pathogenesis of TAO. PMID- 11775839 TI - Comet assay and cytokinesis-blocked micronucleus test for monitoring the genotoxic effects of X-ray radiation in humans. AB - OBJECTIVE: To assess the genotoxic effects of X-ray radiation on human populations. METHODS: The single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus (CBMN) test were applied as biological dosimeters to detect DNA damage and abnormalities in human peripheral lymphocytes of subpopulation exposed to X-ray radiation. The subjects were divided into four groups: 12 radiation-patients; 13 intervention-radiation-therapy doctors; 32 radiation diagnostians; 28 controls. RESULTS: The average comet lengths of the four groups were 128.17 +/- 4.49 microns, 88.09 +/- 5.39 microns, 72.68 +/- 2.57 microns and 32.87 +/- 0.57 microns, respectively. The difference in average comet length between any two groups was highly significant (P < 0.01). The average micronucleated cell (MNC) rates (@1000) of the four groups were 12.33 +/- 0.85, 9.75 +/- 1.02, 8.48 +/- 0.66 and 3.18 +/- 0.36, respectively. The difference of MNC rates of Group 1 vs 3, 1 vs 4, 2 vs 4 and 3 vs 4 was highly significant (P < 0.01), and the difference of Group 1 vs 2 was significant (P < 0.05), but there was no difference of MNC rate in Group 2 vs 3 (P > 0.05). CONCLUSIONS: This study showed that both the comet assay and the CBMN test could be used to monitor populations exposed to X-ray radiation, but the comet assay seems to be more sensitive than the CBMN test. PMID- 11775840 TI - Noninvasive three-dimensional computed tomographic angiography in preoperative detection of intracranial arteriovenous malformations. AB - OBJECTIVE: To assess the value of noninvasive three-dimensional computed tomographic angiography (3D-CTA) in preoperative detection of intracranial arteriovenous malformations (AVMs). METHODS: A prospective evaluation at a single institute over a 2-year period included 23 patients suspected of intracranial AVMs. All patients underwent 3D-CTA and digital subtraction angiography (DSA). Results from both procedures were compared. RESULTS: 3D-CTA imaging provided excellent visualization of intracranial AVMs. The false positive error and false negative error were zero in our sample. The details of arterial supply (numerical measure, orientation, caliber and routing) and vascular nidus (size, morphosis and location) provided by 3D-CTA images were the same as DSA and the details of venous drainage were an approximate match. Additionally, 3D-CTA can depict tridimensional anatomical information for AVMs and their relationship to adjacent structures, a function not possible with DSA. This assisted the surgeons in making better surgical planning and reduced trauma. As a noninvasive course, there were no related-complications in the course of 3D-CTA processing. CONCLUSIONS: DSA is still regarded as the gold standard for intracranial AVMs detection. The modality of 3D-CTA is accurate, noninvasive, nearly risk free and low-price; we could routinely use it instead of or as a supplement to DSA, in the preoperative detection of suspected intracranial AVMs and postoperative radiological follow-up. 3D-CTA adds tridimensional aspect and assists the surgeon in a the more accurate therapeutic scheme. Preliminary data suggest that 3D-CTA is playing a favorable role in the assessment of patients with intracranial AVMs. PMID- 11775841 TI - Chinese-made electrolytic detachable coil in the embolization of a dog aneurysmal model. AB - OBJECTIVE: To develop a Chinese-made electrolytic detachable coil (CEDC) that would allow patients to enjoy the benefit of electrolytic detachable coil without having to rely on the expensive Guglielmi detachable coil (GDC), and to test the safety and efficiency of CEDC. METHODS: Radiopacity of the marker of the CEDC was tested. The anti-strain force of coils and connection points were measured. In vitro and in vivo electrolyses were conducted. We produced 21 aneurysm models including lateral, bifurcation, and terminal aneurysm models, and embolized 18 models with CEDC. RESULTS: Radiopacity of the marker was satisfactory. Anti strain of the coil and the connection point have shown the safety and efficiency of CEDC. Electrolysis in vitro and vivo, was similar to that of GDC. 83% of the aneurysm models were completely occluded. Coils were found to induce thrombosis in the aneurysm cavity, and could lead to a new endothelium over the entrance of the aneurysm, with organized tissue replacing thrombosis in 2 months. CONCLUSIONS: CEDC is as efficient and safe as GDC. The marker, the ability to induce thrombosis inside the sac and the growth of new endothelium over the orifice are very satisfactory. PMID- 11775842 TI - Interventional treatment of huge hepatic cavernous hemangioma. AB - OBJECTIVE: To study the methods of interventional treatment of huge hepatic cavernous hemangioma (HCH). METHOD: A total of 14 patients with HCH were treated with lipiodol-ultrafluid (10-15 ml), bleomycin A (PYM 16-32 mg), and gelatin sponge particles. RESULTS: DSA hepatic arteriography showed multiple vascular lakes in the early arterial phase, so-called "to hang the fruits on the branches", which persisted for a long time. CT scan showed a significant reduction in tumor size in 8 of the 14 patients after the treatment. CONCLUSION: Embolization with lipiodol-ultrafluid, PYM and gelatin sponge particles is one of the best methods for the treatment of HCH. PMID- 11775843 TI - Lymphocytes and perforin expression in endometrium during the menstrual cycle. AB - OBJECTIVE: To study the lymphocytes, perforin protein and mRNA expression in endometrium of different phases in the menstrual cycle and to explore the regularity and role of the lymphocytes and perforin in the reproductive system. METHODS: Immunohistochemical and in situ hybridization techniques were employed to demonstrate the population, phenotype and mediator (perforin) of lymphocytes in the proliferative and secretory endometrium. RESULTS: In different phases of the endometrium, there were very few CD3+ typical T lymphocytes, CD4+ helper lymphocytes and CD8+ suppressor/cytotoxic T lymphocytes, while CD56+ lymphocyte (also named NK-like cell) were abundant. CD56+ lymphocytes were absent in postmenopausal endometrium. A double immunohistochemical labelling method demonstrated the co-expression of perforin protein and CD56 antigen of cells in different phases of the endometrium. Quantitative analysis of CD56+ lymphocytes and perforin-positive cells increased in number from the proliferative to the secretory endometrium (P < 0.05). In situ hybridization analysis showed that perforin mRNA positive cells formed islands in proliferative endometrial stroma, but were scattered in secretory endometrium. There was difference between perforin gene expression and protein expression in the proliferative endometrium. CONCLUSIONS: Lymphocytes and perforin expression in the endometrium at different phases of the menstrual cycle are specific and may play an important role in the reproductive system. They may exert a positive influence on embryo implantation and be involved in endometrial stroma breakdown during menstruation. PMID- 11775844 TI - Enhanced oxidant stress in synovial vessels of patients on hemodialysis. AB - OBJECTIVE: To test the hypothesis that the susceptibility of synovial vessels to redox uncoupling which could result in oxidative damage capable of promoting beta 2-microglobulin (beta 2 m) deposition. METHODS: The expression of oxidative markers by microvascular endothelial cells in hemodialysis (HD) patients, non uremic patients and normal subjects was determined using immunostaining and Northern blotting. RESULTS: Synovial vascular endothelial cells of HD patients exhibited evidence of oxidant stress: induction of malondialdehyde (MDA) epitopes and heme oxygenase. These oxidative markers were not detectable in microvascular endothelial cells of other tissues from HD patients, as well as in the synovial vessels of non-uremic or normal controls. Higher levels of heme oxygenase mRNA in synovia were seen in patients with beta 2 m deposition compared with patients without beta 2 m deposition. CONCLUSIONS: Oxidative damage of the synovial microvasculature in uremic patients may be one of the factors which can promote deposition of beta 2 m in osteoarticular tissue. PMID- 11775845 TI - Effect of superantigen on ion electrophysiology and permeability in rabbit maxillary sinus epithelia. AB - OBJECTIVE: Superantigens are potent inflammatory stimuli which derive from pathogenic microbes such as bacteria, viruses and protozoa. The aim of this study was to investigate the role of superantigens on the function of rabbit maxillary sinus epithelium. METHODS: Twenty New Zealand white rabbits were divided into 4 groups. Rabbit sinus mucosa was separated under a surgical microscope and mounted in Ussing chambers to record short circuit current, conductance and permeability to horseradish peroxidase (HRP). Group A was used as normal control. Group B was stimulated with an injection of superantigen into the sinus for 4 hours. The sinus mucosa of Group C was stimulated by the addition of tumor necrosis factor alpha (TNF-alpha) into Ussing chambers. Group D sinus mucosa was stimulated by superantigen after pretreatment with anti-TNF-alpha antibody. RESULTS: Superantigen evoked increases in sinus epithelial cell baseline short circuit current, conductance and permeability to HRP stimulated by the addition of TNF alpha into Ussing chambers. These were similar to results from superantigen stimulation in vivo. The effect of superantigen on sinus epithelial cells could be blocked by pretreatment with anti-TNF-alpha antibody. CONCLUSIONS: Superantigen affected the function of sinus epithelial cells, including the capability of epithelial defensive barrier, which might be mediated by TNF-alpha. PMID- 11775846 TI - The major achievements of biological products in China. AB - PURPOSE: To review the major achievements of biological products of China in the scientific research and development. DATA SOURCES: The contents of this article were selected from the original essays or reviews related to biologicals published in Chinese and foreign journals. STUDY SELECTIONS: Briefly original articles and reviews of text books published by Chinese authors in the last twenty years were selected. DATA EXTRACTION: These data have addressed the novel vaccines and engineering genetic technologies on biologicals. RESULTS: Nowadays about 200 kinds of biological products are produced in China ranging from preventive vaccines as the majority to therapeutic and diagnostic products. About 800-900 million doses of vaccines for the purpose of prophylaxis are administered annually. Biologicals have played an important role in the prevention of infectious diseases. During the former 30 years the basis for the further development of research work was set up and in the latter 20 years new achievements were made one after another, for example, the development of attenuated JE vaccine, hepatitis A live vaccine, HFRS inactivated vaccine, recombinant HB vaccine and Vi typhoid vaccine, et al. CONCLUSION: During the past 50 years, China has made a great progress in the field of biological products, however we are still week in the aspect of basis research and backward behind the developed countries in originating new products. PMID- 11775847 TI - Recent development in NMDA receptors. AB - PURPOSE: To identify the structure and the function of NMDA receptors, to understand the modulatory mechanism of some endogenous and exogenous compounds on NMDA receptors, and to provide theoretical basis for developing new drugs that modulate NMDA receptors. DATA SOURCES: A total of 24 originally identified articles were selected. STUDY SELECTION: A total of 24 articles were selected from several hundred original articles or reviews. The content of selected articles are in accordance with our purpose and the authors are authorized scientists in the study on NMDA receptors. DATA EXTRACTION: After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria and our experience in the research of NMDA receptors. RESULTS: NMDA receptor contains at least five subunits. They were designated as the NR1 (sigma 1), NR2A (epsilon 1), NR2B (epsilon 2), NR2C (epsilon 3), and NR2D (epsilon 4). A unique feature of NMDA receptor is the requirement for both glutamate and the co-against glycine for the efficient gating. NMDA receptor is modulated by a number of endogenous and exogenous compounds. Mg2+ not only blocks the NMDA channel in a voltage-dependent manner but also potentiates NMDA-induced responses at positive membrane potentials. Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors. Zn2+ blocks the NMDA current in a noncompetitive and a voltage-independent manner. It has been demonstrated that polyamines do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate-mediated responses. The activity of NMDA receptors is also strikingly sensitive to the changes in H+ concentration, and partially inhibited by the ambient concentration of H+ under physiological conditions. regulated by ion channels that are permeable to Ca2+, Na+, K+ and are sensitive to voltage-dependent Mg2+ block. This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord, and is modulated by a number of endogenous and exogenous compounds. NMDA receptors play a key role in wide range of physiologic and pathologic processes. Five NMDA receptor subunits have now been characterized in both rat and mouse brain. PMID- 11775848 TI - Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells. AB - OBJECTIVE: To detect the influence of antisense s-oligodeoxynucleotides (S-ODNs) of bd-2 and multidrug resistance-associated protein (MRP) genes multidrug resistance-associated protein gene and bcl-2 antisense S-oligodeoxynucleotides on cisplatin-resistant lung adenocarcinoma cell line A549DDP which overexpresses both bcl-2 and MRP. METHODS: A549DDP cells were treated with sense and antisense S-ODN mediated by lipofection. Expression of MRP and bcl-2 mRNA and protein in the treated cells was measured by RT-PCR and flow cytometry (FCM), respectively. Apoptosis was identified by DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP nick end-labeling (TUNEL). The degree of drug resistance of the treated cells was detected by a cell viability 3'-[4,5 dimethylthiazol-2-yl]-2, 5-diphenyl-tefrazolium bromide thiazolylblue (MTT) assay. RESULTS: Expression of bcl-2 and MRP significantly decreased in the cells treated with bcl-2 or/and MRP antisense S-ODN for 48 h as compared to the cells untreated and sense-treated (P < 0.05). Resistance to cisplatin in the cells treated with bcl-2 or/and MRP antisense S-ODN decreased by 60.6% (6.5 times), 56.4% (7.2 times) and 71.0% (4.8 times), respectively, which paralleled the decrease of bcl-2 and MRP expression. Similarly, the resistance to etoposide and epirubicin in antisense-treated cells also reduced in parallel to decreases of the two gene expressions. The drug resistance in sense-treated cells was similar to that in untreated cells. Statistically significant dose- and concentration dependent increases of apoptotic cells were observed in the groups exposed to 100 mumol/L cisplatin for 48 h after treatment by bcl-2 or/and MRP antisense. CONCLUSION: Bcl-2 and MRP were at least additive and possibly synergistic in conferring drug resistance in a cisplatin-resistant lung adenocarcinoma cell line. Antisense S-ODN could attenuate drug resistance by promoting cells apoptosis, which might lead to a new treatment for patients with non-small cell lung cancers (NSCLCs) who are refractory to conventional chemotherapy. PMID- 11775849 TI - [Opportunity and challenge in the clinical study of lung cancer]. PMID- 11775850 TI - [Expression of multidrug resistance-associated protein gene in non-small cell lung cancer]. AB - OBJECTIVE: To study the relationship between expression of multidrug resistance associated protein (MRP) gene and occurrence of multidrug resistance (MDR) in non small cell lung cancer (NSCLC). METHODS: Thirty-two NSCLC samples were detected expression of MRP gene and chemosensitivity to 9 antitumor agents by RT-PCR, immunohistochemistry method and in vitro chemosensitivity assay. RESULTS: The positive expression rate of MRP mRNA in NSCLC was 72%, in lung tissue near carcinoma was 10%; the positive expression rate of MRP in NSCLC was 66%, positive staining of MRP located in membrane and cytoplasm of tumor cells, but no positive staining in lung tissue; MRP mRNA and MRP expression of moderate to high differentiation carcinoma was significantly higher than that of low differentiation carcinoma (P < 0.05). There was significant correlation between expression of MRP mRNA and MRP in NSCLC. The expression of MRP in NSCLC, which was resistant to vincristine, etoposide and adriamycin, was higher than that being sensitive to these drugs (P < 0.05). CONCLUSIONS: MRP gene may play an important role of intrinsic drug resistance in NSCLC, overexpression of MRP gene can be achieved through modulation at transcriptional and/or translation level. Overexpression of MRP is a major cause of resistance to vincristine, etoposide and adriamycin. PMID- 11775851 TI - [The diagnostic values of CA242 combining other tumor markers for lung cancer]. AB - OBJECTIVE: To investigate the diagnostic values of CA242, TPA, NSE and CEA tumor markers for lung cancer. METHODS: Using enzyme-linked immunosorbent assay(ELISA). The serum levels of four markers in lung cancer, TB patients and normal subjects (NOR) were measured. RESULTS: Serum concentrations of CA242, TPA, NSE and CEA were significantly higher in patients with lung cancer than patients with TB and NOR (P < 0.01). The sensitivities of CA242 were 65% for adenocarcinoma (AC), 41% for squamous cancer (Sq) and 32% for SCLC, respectively; the specificity was 93%. The sensitivities of NSE were 33%(AC), 41%(Sq) and 71%(SCLC), respectively; the specificity was 97%. The sensitivities of TPA were 65%(AC), 69%(Sq) and 61%(SCLC), respectively; the specificity was 93%. The sensitivities of CEA were 72%(AC), 54%(Sq) and 55%(SCLC), respectively; the specificity was 93%. Using two tumor markers the positive rates were 79% (AC), 54%(Sq) and 63%(SCLC), respectively; the false positive rates in TB and NOR were 7% and 0%, respectively. CONCLUSIONS: Assessing several markers can help differentiating various histological type of lung cancer and can increase significantly the sensitivity and specificity. It is clinically more useful than single marker evaluation. CA242 can be used in diagnosis of lung cancer. PMID- 11775852 TI - [Combined endobronchial and percutaneous radiotherapy after implanting the nitinol alloy endotrachial stent for advanced lung carcinoma]. AB - OBJECTIVE: For the purpose to observe the effectiveness of treatment in late stage patients with bronchogenic carcinoma by implanting nitinol alloy endotrachial stent, combined with endobronchial 192 iridium (Ir) and percutaneous radiotherapy. METHODS: The nitiol alloy endotrachial stent was put into the site of airway stenosis through a special introducer under direct optical fibrobronchoscopy without the help of X-ray examination nor guided steel-line. 192 Ir was inserted to the site of tumor via bronchofiberscope for endobronchial irradiation combining with percutaneous radiotherapy alternately. RESULTS: In all 20 patients, 7 cases (35%) were completely cured and 11 cases (55%) showed partial recovery. The other 2 cases, no change or deteriorated. The 90% effective rate was significantly higher than 60% of control group (P < 0.05). CONCLUSIONS: Dyspnea of patients could be immediately relieved after endobronchial stent was inserted. Combined endobronchial and percutaneous radiotherapy obviously alleviated the obstruction caused by trachial or bronchial neoplasms. The results suggested the combined therapy led to much better objective therapeutic effect and symptomatic relief than single percutaneous radiotherapy. PMID- 11775853 TI - [Adrenal metastasis in primary lung cancer]. AB - OBJECTIVE: To study the incidence, histologic types, clinical symptoms, response rates, and median survival time of adrenal metastasis in primary lung cancer. METHODS: The clinical data were retrospectively evaluated in 96 out of 6,976 patients with adrenal metastasis in primary lung cancer between January 1984 and January 1997. RESULTS: The incidence of adrenal metastasis was 1.38% (96/6,976) in 6,976 patients, 2.25% (37/1,643) in small cell lung cancer, 1.11% (59/5333) in non-small cell lung cancer. Abdominal pain and lumbago (excluding other reasons, for example, abdominal vertebrae and other abdominal organs were involved) occurred in 39% (37/96) in 96 patients. A overall response rate (CR + PR) was 43% in 54 patients who received chemotherapy (5 patients combined with irradiation) and could be evaluated. A median survival time was 7.17 (1-20) months in 96 patients. CONCLUSIONS: Primary lung cancer is easy to spread to adrenals. The incidence of adrenal metastasis is related to histologic types of primary lung cancer. Clinical symptoms include abdominal pain and lumbago. Surgical resection may be applied for a solitary adrenal metastasis after the primary tumor is removed. Chemotherapy is effective for patients with adrenal metastasis synchronous with other sites metastasis. The palliative radiation therapy can produce a high response rate in pain relief. PMID- 11775854 TI - [Effect of antisense oligonucleotides on endothelin converting enzyme expression and endothlin-1 release from airway smooth muscle cells]. AB - OBJECTIVE: To explore the mechanism of TNF-alpha induced ET-1 release and evaluate the effects of endothelin converting enzyme (ECE) antisense oligonucleotides (oDNS) on TNF-alpha induced ET-1 release from airway smooth muscle cells (ASMC). METHODS: ASMC transfected with the antisense oligonucleodides of ECE vectored with lipofectin were established. TNF-alpha induced ECE-mRNA expression and ET-1 release from above cultured cells were determined by RT-PCR and ELISA. RESULTS: ET-1 levels (10.1 +/- 0.3) ng/L and ECE expression (ECE/beta-actin: 0.228 +/- 0.015) in cultured ASMC incubated with 1,000 U/ml TNF-alpha were significantly higher than those in controls without TNF alpha incubation (7.3 +/- 0.8) ng/L, (0.132 +/- 0.032, all P < 0.01). However, after transfecting antisence ECE-oDNS in those cells, ET-1 levels and ECE expressions were significantly lower than those in control cells without antisense transfection. The inhibition rates were (29 +/- 5)% and (35 +/- 12)% respectively. CONCLUSIONS: Abnormal expression of ECE mRNA may be a keypoint responsible for TNF-alpha induced ET-1 release in human ASMC; TNF-alpha induced ET-1 release and ECE mRNA expression from human ASMC are inhibited by antisense oligonucleotide of ECE. PMID- 11775855 TI - [The effects of lipopolysaccharide and anti-inflammatory drugs on nuclear factor kappa B in pulmonary intravascular macrophage]. AB - OBJECTIVE: To investigate activation of nuclear factor-kappa B(NF-kappa B) in pulmonary intravascular macrophage (PIM) stimulated with lipopolysaccharide (LPS) and effects of anti-inflammatory drugs dexamethasone (DEX) and aspirin (ASA) on the process. METHODS: PIMs isolated from three healthy pigs were cultured and divided into four groups: Control group; LPS- stimulated group; DEX- or ASA treated group. The NF-kappa B activity of nuclear protein extract from the PIMs and the concentration of tumor necrosis factor alpha (TNF-alpha) in the supernatant were measured by electrophoretic mobility shift assay (EMSA) and radioimmunoassay (RIA), respectively. RESULTS: The activity of NF-kappa B significantly increased from 0.5 hr to 4 hr after LPS stimulation (P < 0.01); The level of TNF-alpha in the supernatant elevated markedly from 1 hr to 2 hr after LPS stimulation (P < 0.01); positive correlation was found between the NF-kappa B activity and the TNF-alpha concentration at 1 hr after LPS stimulation (r = 0.991, P < 0.01). Compared with LPS-stimulated group, both NF-kappa B activity and TNF-alpha concentration were significantly lowered in DEX- or ASA-treated groups (P < 0.01). CONCLUSIONS: LPS might activate NF-kappa B in the PIMs, and induce the increase of transcription and expression of TNF-alpha gene; Both DEX and ASA could inhibit the activation of NF-kappa B and reduce the release of TNF alpha. PMID- 11775856 TI - [A comparative study of HRCT and digital subtraction bronchography of bronchiectasis]. AB - OBJECTIVE: To assess the value of HRCT in the diagnosis of bronchiectasis at segmental level. METHODS: 29 cases (522 segments) with bronchiectasis doubted by clinical evaluation were selected and HRCT scan and digital subtraction bronchography (DSB) were performed. RESULTS: HRCT and DSB showed a good identity in the diagnosis of bronchiectasis. Of 92 segments diagnosed as bronchiectasis in HRCT, 84 were agreed with DSB; Of 430 segments diagnosed as no bronchiectasis by HRCT, 425 were agreed with DSB. Sensitivity of HRCT is 94%, specificity is 98%. The main HRCT findings were cylindric and cystic bronchiectasis. CONCLUSIONS: HRCT is superior to bronchography for bronchiectasis. It is the first choice of the image diagnostic modalities for the patients in whom bronchiectasis is suspected. PMID- 11775857 TI - [The relationship between smoking and the incidence of COPD]. AB - OBJECTIVE: To study the relationship between smoking index and the incidence of COPD to persuade smokers quit smoking. METHODS: COPD was diagnosed based on family inquiring, questionnaire and pulmonary function test. The smoking index was calculated by the average cigarettes a day times the years of smoking. RESULTS: 822 cases(account for 24.6% of investigated subjects) of COPD due to smoking were identified, and 624 cases were found (account for 40.4% of investegated subjects) to have a history of both smoking and chronic airway inflammation. The higher the smoking index, the higher the incidence of COPD (above 40%), and the more severe their lung function imparement. The smoking was 71.6% of the cause in COPD patients. CONCLUSIONS: The incidence of COPD associated with smoking is higher in China than that in the Western countries. The incidence of COPD in population with long smoking history is not invariable, while it is gradually rising with increasing smoking index. PMID- 11775858 TI - [The experimental study on improved cuirass-respirator]. AB - OBJECTIVE: To study the factors that possibly affect the ventilatory efficiency of cuirass-respirator. METHODS: Cuirass shells were constructed with plaster casts according to the shape of dog's chest wall. Above the cuirass shell, two straps were added in order to hold the cuirass shell when the pump generated pressure. Tidal volume and Pab and Pes were measured during different negative pressure. In addition, tidal volume was recorded before and after the cuirass was held. RESULTS: Ventilatory efficiency was markedly raised after the cuirass was held. As negative pressure rose, ventilation increased and Pdi decreased. CONCLUSIONS: The improved cuirass respirator can markedly improve ventilatory efficiency. PMID- 11775859 TI - [Clinical application of impulse oscillometry]. AB - OBJECTIVE: To discuss the clinical significance of impulse oscillometry(IOS) to determine the resistance of large and small airways and the compliance of lung. METHODS: The IOS indices of 40 normal cases, 50 cases of chronic obstructive pulmonary diseases (COPD) and 60 cases of pleural effusion were determined at 5 35 Hz. Their FEV1/FVC and maximal expiratory flow-volume curve (MEFV curve) were measured in conventional method at the same time. RESULTS: Compared with normal cases, the peripheral resistance of the 50 patients with COPD rose obviously and the central airway resistance rose in some of them, the resonance frequency increased, but the peripheral reactance descended at the same time (P < 0.01). Resistance curve show markedly nonlinear decreasing course with increasing frequency. The resistance increased and the reactance descended in end expiration. FEV1/FVC < 50%, MEFV curve showed severe obstructive shape. 60 patients with pleural effusion were found the resistance increasing and reactance descending to negative values in end-inpiration at low frequencies (inverse values relation at low frequencies). FEV1/FVC were nearly normal, MEFV curve showed restrictive dysfunction shape only in half of them. CONCLUSIONS: IOS can reflect variation of airway resistance and lung compliance. The future development of IOS could be prosperous. PMID- 11775860 TI - [Direct, rapid detection for rifampin susceptibility to M. tuberculosis]. AB - OBJECTIVE: To evaluate the use of molecular biotechnology for direct, rapid detection of rifampicin-resistance mutations in M. tuberculosis. METHODS: 45 M. tuberculosis clinical isolates and 70 sputum samples were tested by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) technique. M. tuberculosis strain H37Rv was used as control and compared with the result of susceptibility test. DNA sequencing was also performed in some of the strains. RESULTS: All tested susceptible isolates displayed identical SSCP patterns. Of 29 RFP resistance strains, 26(90%) had distinct mobility shifts that can be discriminated from susceptible isolates. 9 sputum samples which were succeasfully evaluated by PCR-SSCP showed concordant result acquired from BACTEC 460 method. As the result of DNA sequencing, it was observed that seven RFP-resistance phenotype of M. tuberculosis strains had missense mutation, in which 5 isolates displayed TCG-->TTG or CAG mutations at codon 531.2 had CAC-->TAC mutation at codon 526. On the other hand, one strain which was susceptible to rifampin exhibited identical nucleotide alignment to the sequence of rpoB gene. CONCLUSIONS: PCR-SSCP could be used as a method for simple, rapid, and reliable detection of rifampicin-resistance mutations in clinical samples of M. tuberculosis. PMID- 11775861 TI - [Optic nerve neuropathy by ethambutol toxicity]. AB - OBJECTIVE: To investigate the clinical manifestations, treatment and prevention of optic nerve damage by ethambutol toxicity. METHODS: Retrospective analysis was done on 17 patients of tuberculosis who had been treated with ethambutol and shown ocular symptoms. RESULTS: Changes in visual acuity, fundal appearance, visual field and color sensation were major abnormal findings. According to the neural damage, the patients were diagnosed as axial neuritis 7 cases, periaxial neuritis 2 cases, mixed type 3 cases and there were no significant changes on fundus, color sensation or visual field in 5 cases. In 17 cases, none of the patient showed the appearance of retinitis. The impairment of visual acuity and the duration of damage were related to the daily dosage significantly. After stop of ethambutol and vasodilators or neurotrophic drugs were given, the function of optic nerves were recovered. CONCLUSIONS: To prevent the damage of optic nerves by the toxicity of ethambutol, the appropriate small dosage of ethambutol is recommended, regular examination and monitoring of visual function is necessary. The physicians should be fully aware of the diagnosis and clinical manifestations of ocular toxicity of ethambutol, as soon as the diagnosis is made, ethambutol should be stopped immediately and appropriate therapy should be given. PMID- 11775862 TI - [The current status of the study on asthma in China]. AB - PURPOSE: To review the recent developments in asthma research in China, presenting the background of further asthma research and promoting academic exchanges between Chinese and foreign respirologists. DATA SOURCES: A literature search was conducted using 5 authoritative journals covering the years 1994-1998. STUDY SELECTION: Sixty-seven of 238 asthma-remated original articles published between the years 1994-1998 were selected to reflect the recent developments in asthma in China. DATA EXTRACTION: The papers reviewed pertain mainly to the epidemiology, genetics, pathogenesis, prevention and treatment of asthma. RESULTS: Since 1993, the hot topics in asthma research in China have been pathogenesis, prevention and treatment. There has been relatively less investigation into the genetics of asthma in China. An epidemiological survey of asthma has been conducted in parts of China and was reviewed. CONCLUSIONS: More and more attention has been paid to the study of asthma during the last five years in China. The prevalence of asthma has increased in recent years. The study of the pathogenesis of asthmatic airway inflammation has made further progress, which will help the management and treatment of asthma. The treatments for asthma, including herbal medicine, have been explored and the clinical efficacy of inhaled corticosteroids has been established. PMID- 11775863 TI - [Automatic modulation of refractoriness of His-Purkinje system during atrioventricular nodal reentrant tachycardia]. AB - OBJECTIVE: To illustrate the automatic modulation of refractoriness of His Purkinje system during atrioventricular nodal reentrant tachycardia (AVNRT) and to discuss the possible mechanisms. METHODS: Programmed electrical stimulations were performed in high right atrium (HRA) in 8 patients with AVNRT before ablation to induce tachycardia and electrocardiagraphic recordings were done synchronically when AVNRT appeared. RESULTS: All the patients had 2:1 atrioventricular (A-V) conduction when AVNRT began, 2 of whom were blocked below His bundle, 5 above His bundle and 1 unclear. After a duration of 14.03 +/- 10.03 s of 2:1 A-V conduction, 1:1 A-V conduction with bundle banch block appeared, 3 of which were right bundle branch block (RBBB), 3 left bundle branch block (LBBB), and 2 with both. Bundle branch block disappeared after a duration of 6.87 +/- 11.26 s. CONCLUSION: Effective refractory period (ERP) of His-Purkinje system at the beginning of AVNRT was modulated automatically within less than 30-60 s and thus facilitated nodal-ventricular conduction. The mechanism of this is electrical remodeling. PMID- 11775864 TI - [Relationship between isometric exercise and myocardial ischemia in patients with coronary artery disease: an Echo-Doppler study]. AB - OBJECTIVE: To study the relationship between isometric exercise and myocardial ischemia in patients with coronary artery disease (CAD). METHODS: Twenty CAD patients and 10 normal subjects were included in our study. All subjects performed maximal brief isometric exercise (BIE), maximal sustained isometric exercise (SIE) and dynamic exercise (DE). Hemodynamic parameters and cardiac function were measured by Echo-Doppler technique. To avoid influence of different baseline values, increment (delta%) of exercise response was used as parameter for significant analysis: delta% = (exercise values - baseline values)/baseline values x 100%. RESULTS: Positive exercise testing (PET) showed no evidence of myocardial ischemia during BIE and SIE even though their rates of perceived exertion (RPE) were similar to DE. delta% heart rate (HR) and delta% rate pressure product (RPP) were higher during DE than during SIE and BIE in negative exercise testing (NET) and normal controls (NOR) (P < 0.01), except PET during DE and SIE; delta% systolic blood pressure (SBP) was higher during DE than during BIE in NOR (P < 0.01). delta% SBP in NOR and NET during SIE was higher than during BIE (P < 0.05). delta% diastolic blood pressure (DBP) was the highest during SIE among exercises in all gropus (P < 0.05). There were no significant inter-group differences of delta% HR, delta% SBP, delta% DBP and delta% RPP during SIE, BIE and DE, except that delta% SBP during SIE was higher in NET than in NOR and PET (P < 0.05). In NOR, delta% ejection fraction (EF), delta% fractional shortening of the minor-semi axis (SF), delta% cardiac output (CO), delta% E/A was higher during DE than during SIE and BIE (P < 0.01). delta% stroke volume (SV) was similar during DE, SIE and BIE. There were no significant differences in delta% EF, delta% SF, delta% CO, delta% SV and delta% E/A during DE, SIE and BIE in both NET and PET, except lower delta% CO in NET during SIE and BIE than DE (P < 0.01). There were no inter-group differences in delta% EF, delta% SF, delta% CO and delta% E/A, except that delta% E/A was higher during SIE in NET than PET (P < 0.01). During DE, NOR and NET had higher delta% SV, delta% SF, delta% CO and delta% E/A than PET (P < 0.05). CONCLUSIONS: The incidence of myocardial ischemia in CAD patients was lower during isometric exercise than dynamic exercise at similar perceived exertion levels. Isometric exercise might protect the myocardium from ischemia through high coronary artery perfusion pressure and long perfusion duration. We suggest that application of isometric exercise in a cardiac rehabilitation program may have reasonable physiological background. PMID- 11775865 TI - [Potentiation of arsenic trioxide-induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells]. AB - OBJECTIVE: To study the effect of arsenic trioxide (As2O3) on non-APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and As2O3. METHODS: RA-sensitive (S) and RA-resistant (R) HL-60 non-APL AML cells were used as an in vitro model. Cell number and trypan blue were used to observe cell growth and survival. Apoptosis was determined by morphological changes, using a DNA laddering assay, terminal deoxynucleotidyl transferase (TdT) fragment end labeling assay and a flow cytometry assay. RESULTS: As2O3 induced apoptosis in both HL-60S and HL-60R cells, As2O3-induced apoptosis was both time- and concentration-dependent in a therapeutically-achievable As2O3 range (0.25-4.0 mumol/L). Both all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA) potentiated As2O3-induced apoptosis, as measured by quantitative TdT fragment and labeling and flow cytometry assays in both HL-60S and HL-60R cells (P < 0.05, for all RA + As2O3 combinations vs As2O3 alone in both sublines). CONCLUSIONS: As2O3 may inhibit the growth of non-APL AML cells by promoting programmed cell death. RA can potentiate As2O3-induced apoptosis even in RA-resistant HL-60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor alpha. As2O3 can have clinical activity in non-APL cases of AML and the enhanced activity might result from the combined As2O3-RA therapy. PMID- 11775866 TI - [Aberrant expression of MUC2 and MUC3 genes in gastric carcinoma and its significance]. AB - OBJECTIVES: To explore the clinicopathological significance of the expression of MUC2 (mucin 2) and MUC3 (mucin 3) genes in tissues of the normal gastric mucosa, intestinal metaplasia (IM) and gastric carcinoma. METHODS: MUC2 and MUC3 apomucins were detected by immunohistochemistry; MUC2 and MUC3 mRNAs were detected by in situ hybridization. RESULTS: In the normal stomach, antibody detecting MUC2 apomucin and oligonucleotide probe detecting MUC2 mRNA were not reactive with mucus-producing cells in the superficial epithelium and neck, which were weakly reactive with antibody and probe detecting MUC3. In the duodenum, MUC2 apomucin and mRNA were found at the peri- and supranuclear area of goblet cells, but MUC3 apomucin and mRNA were at the cytoplasm of goblet cells and columnar cells. MUC2 and MUC3 apomucins and its mRNAs were found in 85.2%, 88.9% and 31.6%; 57.1% of specimens of IM, 67.4%, 66.7% and 57.9%, 43.6% of specimens of gastric carcinoma. There were no associations between expressions of MUC2 and MUC3 genes and different types of IM. Patients with moderate/well differentiation had higher proportion of MUC2 apomucin expression than those with poor differentiation (P < 0.05), and patients with positive staining of MUC3 apomucin in the cancerous tissues had higher proportions of metastasis of lymph nodes (P < 0.01), serosal invasion (P < 0.05) and clinical stages III-IV (P < 0.05). CONCLUSIONS: MUC2 and MUC3 genes are mainly expressed in the mucosa of the duodenum, and marked expression is seen during the neoplastic transformation of stomach mucosa. MUC3 apomucin might have a poor prognostic significance. PMID- 11775867 TI - [Regulation of the expression and function of glucose transporter-1 by TGF-beta 1 and high glucose in mesangial cells]. AB - OBJECTIVE: To study the effects of high glucose and transforming growth factor beta 1 (TGF-beta 1) on the expression and function of glucose transporter-1 (GLUT1) in mouse mesangial cells. METHODS: Cultured mouse mesangial cells were used. The expression of GLUT1 mRNA was detected by Northern Blot; glucose uptake and its kinetics were determined with a 2-Deoxy-[3H]-D-glucose uptake assay. RESULTS: Mesangial cells exposed to enriched glucose medium (20 mmol/L) for 72 hours demonstrated a decrease in both GLUT1 mRNA and Vmax for uptake of the glucose analog, 2-deoxy-D-glucose (2DOG), as compared to mesangial cells cultured in physiologic glucose concentrations (5.5 mmol/L). In contrast, hypertonic mannitol had no effect on GLUT1 mRNA levels. TGF-beta 1 treatment for 10 hours stimulated 2DOG uptake, both in 5.5 mmol/L and 20 mmol/L glucose medium, by approximately 4.28-fold in a dose-dependent manner (2 ng/ml maximum). Kinetic analysis of 2DOG uptake revealed an increase in Vmax and a decrease in Km in the presence of TGF-beta 1. TGF-beta 1 also up-regulated the expression of GLUT1 mRNA in mesangial cells. The addition of anti-TGF-beta neutralizing antibody (30 micrograms/ml) in mesangial cells cultured in enriched glucose medium (20 mmol/L) led to a 40% decrease in 2DOG uptake. CONCLUSIONS: The expression of GLUT1 can be suppressed by exposure of mesangial cells to high glucose medium, which may serve as a protective mechanism against possible adverse effects of excessive glucose flux into cells. TGF-beta 1 stimulates glucose uptake by enhancing the expression and function of GLUT1 in mesangial cells. This effect is independent of the glucose milieu in the cultured medium. PMID- 11775868 TI - [WHO: the major impact of tobacco is on health, not on small tobacco growers]. PMID- 11775869 TI - [AP-1 mediated signal transduction in thrombin-induced regulation of PAL-1 expression in human mesangial cells]. AB - OBJECTIVE: To evaluate activator protein-1 (AP-1) mediated mechanisms in thrombin induced qlasminogen activator inhibitor-1 (PAI-1) expression in cultured human glomerular mesangial cells (MCs). METHODS: Electrophoretic mobility shift assay (EMSA) was employed to assess AP-1 DNA-binding activity, and Western blot hybridization was used for quantification of c-fos and c-jun, two subunits of AP 1 dimers. PAI-1 activity and mRNA expression were analysed by the fibrin plate assay and Northern hybridization, respectively. RESULTS: Thrombin concentration enhanced PAI-1 activity in the supernatant and stimulated PAI-1 mRNA expression in cultured MCs. PAI-1 activity was blocked by hirudin, a specific inhibitor of thrombin. Further study demonstrated that thrombin promoted AP-1 DNA-binding activity but exerted little effect on c-fos or c-jun. Curcumin (AP-1 inhibitor), staurosporine (PKC inhibitor), and genistein (PTK inhibitor) all reduced AP-1 mediated PAI-1 mRNA expression induced by thrombin in cultured MCs. CONCLUSION: The present study indicates that in cultured human MCs, thrombin stimulates PAI-1 expression through an AP-1 signal pathway, which may be mediated by PKC and PTK. PMID- 11775870 TI - [Changes after dynamic observation of ultrastructural cerebral infarction in renovascular hypertensive rats]. AB - OBJECTIVE: To study the ultrastructural damages of brain tissues dynamically after middle cerebral artery obstruction (MCAO). METHODS: A middle cerebral artery obstruction (MCAO) model was reproduced in renal vascular hypertensive rats (RHR). Brain tissues in different locations were collected for eight times in row, from two hours to seven days after establishment of the animal model. RESULTS: The changes occurred in the whole brain after focal cerebral ischemia. The severity of impairment and time of emergence differed with the location sampled. The earliest in the infarcted region with necrosis was considered the major change and completely irreversible damage. The next was seen in marginal regions, mainly with microvascular collapse, formation of microthrombi, and partial necrosis of brain cells and was considered partially reversible damage. The last was in distant and contralateral hemisphere, mainly with reversible swelling of endothelial cells and astrocytes. Changes in the MCAO models reproduced by RHR models were much similar to the clinical pathological changes in cerebral infarction based on the hypertensive cerebrovascular impairment, and it was regarded as a relatively ideal model for studying focal ischemic cerebral impairment. CONCLUSION: Dynamic changes of cerebral ultrastructure in which microvascular impairment plays an important role suggest that clinical therapy cannot only be focused on infarction foci, but also on the whole brain with comprehensively effective measurements. PMID- 11775871 TI - [Expression of telomerase and its RNA in nasopharyngeal carcinoma]. AB - OBJECTIVE: To study the activity of telomerase and the expression of its RNA in nasopharyneal carcinoma (NPC) and HNE1 cell lines of NPC. METHODS: Telomerase activity was detected with telomeric repeat amplification protocol (TRAP) PCR ELISA kit in 41 cases of NPC, 14 cases of tissues adjacent to the carcinoma, and 19 cases of chronic nasopharyngitis, HNE1 cell lines of NPC, HL60 cell lines of leukemia, TUL1 cell lines of lung cancer, as well as three other kinds of normal control cells. The sensitivity and specificity of telomerase assay were also analyzed. Moreover, the expression of human telomerase RNA (hTR) was studied in 27 cases of NPC, 19 cases of adjacent nasopharyngeal tissues, and 17 cases of control groups by RT-nested PCR. RESULTS: The telomerase activity was found increased in NPC and in tissues adjacent to NPC with absorbance value (A value) of 1.15 U +/- 0.78 U and 1.04 U +/- 0.67 U respectively, compared with chronic nasopharyngitis (A = 0.18 U +/- 0.09 U). In NPC with cervical lymphnodes involvement the telomerase activity (A = 1.25 U +/- 0.79 U) was higher than in those without involvement (A = 1.02 U +/- 0.71 U), P < 0.05. The telomerase activity was also observed in HNE1 cell lines (A = 1.26 U +/- 0.97 U) and in other two kinds of cancer cell lines, but not in the three kinds of normal control cells. By contrast, no significant difference was seen in the expression of hTR among the three nasopharyngeal biopsy groups (P > 0.05). Finally, the sensitivity of telomerase assay was high (at an amount of 10(2) HNE1 cells), and the specificity was also high (after inactivation by heat or RNase, the telomerase activity was very low). CONCLUSIONS: A high frequency of telomerase activity is commonly seen in NPC, adjacent nasopharyngeal tissues, and HNE1 cell lines and is closely associated with NPC with cervical lymphnodes involvement. Both sensitivity and specificity of the telomerase assay are high. However, owing to the fact that the expression of hTR has no obvious difference between NPC and normal tissues and does not always correspond with the telomerase activity, it would be better to do TRAP as well as hTR assays for the activity and expression in assessing the carcinogenesis of NPC. So, more intensive study on the role of hTR in the carcinogenesis of NPC and on the exact relationship between hTR and telomerase is needed. PMID- 11775872 TI - [Rhubarb extracts in treating complications of severe cerebral injury]. AB - OBJECTIVE: To investigate the therapeutic effects of the Chinese medicinal herb, Rhubarb, on severe brain injury. METHODS: Rhubarb extracts in ethyl alcohol and water were used to treat 20 patients with severe cerebral injury complicated by hyperthermia, renal failure, hemorrhage in the upper digestive tract, and increased intracranial pressure. Vital signs, variations of Glasgow coma scale (GCS) and intracranial pressure (ICP) of the patients were observed. The degree of hemorrhage in the digestive tract and the change in creatinine value were also observed. Other 20 patients served as controls. RESULTS: The result of the treatment group was more marked than that of the control group. Three days after administration of the rhubarb extract, the body temperature decreased by 1.1 degrees C, ICP by 0.4 kPa (1 mm Hg = 0.1333 kPa) on average, and the incidence of hemorrhage in the digestive tract by 30%. The volume of hemorrhage of the digestive tract decreased by 700 +/- 250 ml, and the time for turning occult blood to negative by 10%. CONCLUSION: The Chinese medical herb, rhubarb, has multiple therapeutic effects on severe brain injury. PMID- 11775873 TI - [A comparison of malignant fibrous histiocytoma of head, neck and extremities]. AB - OBJECTIVE: To compare the epidemiology, local and regional invasion and prognosis of head and neck, malignant fibrous histiocytoma (MFH) and extremity MFH. METHODS: Between January 1, 1972 and December 31, 1993, 173 patients with MFH (71 head and neck, 102 extremities and trunk) were referred to the Cancer Hospital for surgical treatment. They were 101 men and 72 women, with age ranging from 13 to 83 years (median: 45 years). The extent of surgery was classified into radical, wide and local resection. RESULTS: For head and neck, local recurrence of MFH after wide resection was 80.4% (37/46), compared with 36.4% (8/22) after radical surgery (P = 0.000). The five-year survival was 50.79% in all the head and neck patients (74.75% in patients free of local recurrence, 37.74% in patients with local recurrence; P = 0.0181), compared with 70.71% in extremity patients (P = 0.0005). Repeated surgery after recurrence of MFH could cure 40.9% of the head and neck patients and 80.7% of the extremity patients. CONCLUSION: Inadequate resection of head and neck MFH in initial surgery is associated with a high incidence of local recurrence, which is always correlated with worse prognosis. Repeated surgery for recurrent head and neck MFH is not as effective as for recurrent extremity MFH. Therefore, we suggest that the initial surgery for head and neck MFH should be as radical as allowed to avoid a possible local recurrence. PMID- 11775874 TI - Unsafe injection practices have serious, large-scale consequences. PMID- 11775875 TI - [Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell]. AB - OBJECTIVE: To observe the effect of the transfer of multidrug resistance gene (mdr1) into human hematopoietic progenitor cells (HPC) on the chemoprotection. METHODS: Human CD34+ cells served as a target of mdr1 gene transfer. Retroviral vector SF-mdr containing human total length mdr1cDNA was introduced into packing cells GP-envAM12 by liposome-mediated transfection. The mdr1 gene was transduced into human CD34+ cells by retroviral supernatants of packing cells. The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT-PCR, and flow cytometry. The drug resistance of chemotherapy in transduced HPC was determined by culturing colonies. RESULTS: The mdr1 gene was integrated and expressed in transduced CD34+ cells. The efficiency of mdr1 gene transfer was 10%-14%. Compared with untransduced controls, within a certain range of drug concentration, the number of drug-resistant colony in transduced HPC for taxol, doxorubicin, VCR and VP16 were increased by 3.6 +/- 2.1 fold, 2.9 +/- 0.3 fold, 1.9 +/- 0.4 fold, and 3.5 +/- 0.5 fold, respectively. CONCLUSION: The transfer of the mdr1 gene into human HPC can increase the drug resistance of the transduced cells to corresponding chemotherapeutic drugs that may provide some degree of chemoprotection for HPC. PMID- 11775876 TI - Acute fatty liver of pregnancy: diagnosis and management of 8 cases. AB - OBJECTIVE: To investigate the early recognition and management of acute fatty liver of pregnancy (AFLP) to improve maternal and fetal survival. METHODS: Eight cases of AFLP seen in our hospital during the past three years were studied retrospectively. Symptoms, laboratory findings, timing of liver biopsy, and maternal and fetus outcome were assessed. RESULTS: The mean gestational age at onset was 34 +/- 2 weeks. All cases were primigravida. In the early stages, all patients presented malaise, nausea, vomiting and epigastric distress followed by jaundice in the third trimester of pregnancy. LABORATORY FINDINGS: all had raised transaminases and serum bilirubin (32.5-510.8 mumol/L), hypoalbuminemia (22.4 30.0 g/L), hypofibrinogenemia (< 180 mg/dl), prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complication included hepatic encephalopathy (6 cases), ascites (6), hypoglycemia (5), hematemesis (2), and postpartum hemorrhage (5) and preeclampsia (4). Emergency cesarean section was performed in 3 cases. One mother died of fulminant hepatic failure and the others survived. There was no fetus death. Liver biopsy was done on the 5th to 15th postpartum day in 8 cases. CONCLUSION: With increasing awareness, especially in the early recognition of milder cases, and prompt progressive management including early termination of pregnancy by cesarean section and large dose infusion of fresh frozen plasma and albumin alternately, the prognosis of AFLP can be improved. PMID- 11775877 TI - [Long-term monitoring of artificial vagina reconstructed with sigmoid colon]. AB - OBJECTIVE: To observe the influence of the artificial plastic vagina on overall patient health. METHODS: Length and width of the artificial vagina were measured. Histological studies were performed under light and electron microscope. Vaginal bacterial flora were analyzed using the drop-implant method. Vaginal HPV and ER were detected with ABC histochemical staining. RESULTS: According to the results of anatomic measurements, artificial vagina was similar to normal vagina. The reductions of glands in the mucosa and collagen fibers as well as interstitial tissue hyperplasia in the lower segment of artificial vagina were documented. Four kinds of bacteria indigenous to the sigmoid colon were found in artificial vagina and were studied microbiologically with only differences in the amount and detection rates of bacteria flora. The positive presentation of HPV was not significantly different from that in the control group. The positive presentation of estrogen receptor (ER) in the epithelium of artificial vagina was not found. CONCLUSION: The reconstruction of artificial vagina with sigmoid colon is a safe, effective and satisfactory procedure for the patient. PMID- 11775878 TI - [Field epidemiological and experimental study on relationship between genetic factor and nonresponse or hyporesponse to hepatitis B vaccine]. AB - OBJECTIVE: To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study. METHODS: Six hundred and thirty-four susceptible healthy students were vaccinated with three doses of plasma-derived hepatitis B vaccine. Twenty-nine non- or hypo-responders (subjects) and 30 hyperresponders (controls) as well as their 80 and 79 first degree relatives were determined and recruited in the study. The first degree relatives of subjects and controls were then immunized with hepatitis B vaccine and followed up. On the basis of the above results, alleles of HLA-A, B, C, DR and DQ locus were further detected in the two groups. RESULTS: The non- and hypo-response rate in immunized students was 4.6% (29/634). After administered with hepatitis B vaccine, the first degree relatives of the subjects displayed a 17.9% frequency of nonresponsiveness, higher than in the controls. The phenotype frequency of HLA DR7 and B54 was 52.2% and 21.7% in subjects, 9.1% and 0.0% higher than in controls, respectively. The extended haplotype B54-DR7 was more frequent in the former (17.0%) than in the latter (0.0%) (P < 0.01). CONCLUSION: These results demonstrated that the genetic factor was likely associated with the non- and hypo response to hepatitis B vaccine in Chinese people. PMID- 11775879 TI - [Some geographical features of the location and gene mutation of cancers occurring in Nantong City, China]. AB - OBJECTIVE: To detect the location and geographical features of gene mutation of the cancer based on 30,709 clinical tumor biopsies. METHODS: Thirty thousand seven hundred and nine cases of tumor biopsy materials were collected from the Department of Pathology of Nantong Cancer Hospital between June 1974 and December 1987. The address of the village and county of patients was collected and statistical analysis was performed on data from lab examination. DNA sequencing of 31 cases of hepatocellular carcinoma (HCC) was performed at the Department of Pathology of the Medical College of Tokyo University, Japan. RESULTS: The data suggested that different carcinomas occurred predominantly in some districts and the frequency and type of mutation of the P53 gene in the HCC were different in different districts. CONCLUSION: It seems that based on the clinical biopsy materials, carcinomas of the uterus cervix (CC) and nasopharynx tend to occur in some districts of Nantong City and the frequency and type of mutation of the gene P53 of the HCC were different in different districts. The reason for this is not understood and further study will be done. PMID- 11775880 TI - [Gibbs-Sampler approach for meta-analysis of multiple clinical trials using generalized linear model with random-effects]. AB - OBJECTIVE: To investigate the use of the Gibbs-Sampler method in evaluating the relationship between clinic events and health risks in a meta-analysis of multiple clinical trials. METHODS: By using a generalized linear model with random-effects, Gibbs-Sampler technique was used in a meta-analysis of multiple clinical trials of angiotensin converting enzyme (ACE) inhibitors in patients with myocardial infarction (MI). RESULTS: When heterogeneity across different trials can not be ignored, compared with the classic method, the odds ratio of relative reinfarction risk estimated by the Gibbs-Sampler method would have less variation. The gain in the reduction of variation in estimate of the overall odds ratio was 9.52%. CONCLUSION: Implementation of the Gibbs-Sampler technique in meta-analysis of multiple clinical trials has the potential of reducing the inaccuracy caused by heterogeneity across trials. PMID- 11775881 TI - [Effect of melatonin on the spatial and temporal changes of [Ca2+]i in single living cells of cortical neurons by laser scanning confocal microscopy]. AB - OBJECTIVE: To examine the effects of melatonin on the dynamic changes in the concentration of intracellular free Ca2+ ([Ca2+]i) in single intact cultured cortical neurons isolated from fetal rats, in order to explore the possible antiaging mechanisms of melatonin (MT). METHODS: Using the highly fluorescent Ca(2+)-sensitive indicator Fluo-3/AM, cortical neurons cultured in a 35 mm Tissue Culture Dish were in incubated for 45 min at room temperature with 5 mumol/L Fluo 3/AM, resulting in proper intracellular dye concentration to provide adequate signal strength for detection and excellent Laser Scanning Confocal Microscopy (LSCM) imaging of [Ca2+]i while not disturbing normal intracellular physiology. The changes in fluorescent intensity were monitored by LSCM. RESULTS: Bay K8644 (10(-6) mol/L), KCl (20 mmol/L), sodium L-glutamate (Glu, 50 mumol/L) caused a rapid increase of [Ca2+]i in cortical neurons, and this increase could be significantly attenuated by 10(-6) and 10(-7) mol/L MT. CONCLUSIONS: MT could antagonize the extracellular Ca2+ influx, reduce Ca2+ overload, and have a protective effect on neurons. This may be one of the important antiaging mechanisms of MT. PMID- 11775882 TI - [Retroviral transduction of a mutant erbB-2 gene into human CD34+ derived dendritic cells]. AB - OBJECTIVE: To successfully transduce a mutant erbB-2 gene into normal human CD34(+)-derived dendritic cells (DCs) and verify gene expression in these transduced dendritic cells. METHODS: The packaging cell line PA317 was transfected with mutant erbB-2 gene DNA and the virus produced was used to infect packaging cell line PG13. The virus produced by PG13 was used to infect CD34(+) derived dendritic cells by the spinoculation method using flasks coated with fibronectin material to facilitate retrovirus gene transter efficiency and the mutant erbB-2 gene expression was assessed by ABC staining and FACScan methods. RESULTS: A mutant erbB-2 gene packaging cell line was produced and this mutant gene was transduced into human CD34(+)-derived DCs. It was verified that the relatively large numbers of the transduced DCs expressed the mutant erbB-2 protein which was eradicated of the ability to transform mouse NIH3T3 fibroblast cells. CONCLUSIONS: Human DCs can be gene-modified and these gene-modified DCs may be useful in stimulating T lymphocytes for immunotherapy. PMID- 11775883 TI - [A new look at the mechanism of cholera endemicity caused by Vibrio cholerae biotype eltor]. AB - OBJECTIVE: Cholera caused by Vibrio cholerae biotype eltor (EVC) is an endemic disease, subsiding in winter and reappearing in spring and summer. Investigating the state of EVC during the intermittent time is of crucial importance in controlling this disease. METHODS: Different factors mimicking the internal and external environmental conditions of the host, including human and fish bile, bacterial phages and antibiotics were used experimentally to induce variation in EVC. EVC variants were isolated from the stool of diarrhea patients and river water in old endemic areas during the winter. The variants obtained were tested with gene probe hybridization, DNA restriction enzyme mapping, immunoenzyme staining and animal passaging. RESULTS: Due to the loss of cell walls, 3 kinds of EVC variants were obtained during induction: the L-form variant, with a complete loss of cell walls; the nonagglutinating variants, with the loss of surface O antigen; the phage-resistant variants, with the loss of phage receptors. Similar variants were found in field isolation. This variation was proved to be phenotypic, with no change in genetic material: it was reversible and appeared in a seasonal pattern, which coincided with the endemicity of this disease. Passage in animal enhanced this reversion. In compensation for the loss of cell walls, cell membranes were greatly thickened, increasing the ability of the variants to survive during the unfavorable winter conditions. CONCLUSIONS: EVC varied in a seasonal pattern, coincident with the endemicity of this disease. The compensatory thickening of the cell membranes protects the EVC variants to survive the winter. PMID- 11775884 TI - [Malignant melanoma of uterus]. PMID- 11775885 TI - [A Chinese family with autosomal dominant retinitis pigmentosa and a pro347Leu rhodopsin gene mutation]. PMID- 11775886 TI - [More efforts should be paid to the study on etiology of pregnancy induced hypertension]. PMID- 11775887 TI - [The association between A1166-->C of angiotensin II type 1 receptor gene and pregnancy induced hypertension]. AB - OBJECTIVE: To determine the distribution of gene type of A1166 polymorphism site of the angiotensin II type 1 receptor gene (AT1RG) and whether it might be implicated in pregnancy induced hypertension (PIH) woman. METHODS: We used polymerase chain reaction (PCR), restriction enzyme analysis and electrophoresis for this study. RESULTS: 1. The gene types of A1166 polymorphism site of AT1R gene on normal control and PIH and essential hypertension subjects were in accordance with Hardy-Weinberg laws. 2. The C allele frequencies of AT1R gene (A1166-->C) in control, PIH, and essential hypertension subjects was 3.7%, 11.4%, and 9.4%, respectively. 3. The frequency of variants(AC, CC) of AT1R gene A1166 polymorphism site in PIH (20.5%) was significantly higher than that of control subjects (7.4%). 4. The gene type of variants (AC, CC) and C allele frequency of AT1R gene A1166 polymorphism site in essential hypertension (18.8%, 9.4%, respectively) was higher than those of control subjects. There is no statistical difference in A1166-->C variants between PIH and essential hypertension. CONCLUSIONS: 1. The variants(A-->C) of 1166 polymorphism site of AT1RG predisposes increased risk of PIH. 2. The PIH patients are at the risk of suffering from essential hypertension. PMID- 11775888 TI - [Changes of plasma levels of type C natriuretic peptide in patients with pregnancy induced hypertension]. AB - OBJECTIVE: To investigate the changes and clinical significance of plasma type C natriuretic peptide (CNP) concentration in patients with pregnancy induced hypertension (PIH). METHODS: Plasma CNP levels were detected by radioimmunoassay in 89 patients with PIH, 193 normal pregnant women and 46 normal non-pregnant women. Outcomes were statistically analyzed by one-way analysis of variance and Student-Nawman-Kenls (SNK) test. RESULTS: The plasma CNP levels in patients with PIH [(30.51 +/- 33.61) ng/L] were significantly higher than those of normal non pregnant women and normal pregnancies [(17.15 +/- 3.82) ng/L, (19.43 +/- 5.13) ng/L, respectively; F = 13.61, P < 0.01]. There was significant difference among plasma CNP levels from patients with mild, moderate, and severe PIH (P < 0.0001). CONCLUSIONS: The changes of plasma CNP levels are believed to be the reflection of patients in progression of PIH and can be used as a biochemical marker for judging the progression and guiding the therapy of PIH. PMID- 11775889 TI - [The study on correlation of c-myc expression with vascular smooth muscle cell proliferation in uterine spiral arteries of pregnancy induced hypertension]. AB - OBJECTIVE: To investigate c-myc proto-oncogene expression of uterine spiral arteries in pregnancy induced hypertension (PIH) and the relationship of this expression with vascular smooth muscle cell (VSMC) proliferation in uterine spiral arteries of PIH. METHODS: Forty-nine placental bed biopsies, 29 from women with PIH and 20 from normotensive pregnant women, were taken during cesarean section. The expression of c-myc in uterine spiral arteries was detected and localized by in situ hybridization. Histological changes of placental bed biopsies were evaluated by HE staining. RESULTS: The positive rate of c-myc was 63.6% (7/11) in moderate PIH and 72.2% (13/18) in severe PIH respectively. They were significantly higher than that in normotensive pregnancy (P < 0.05, P < 0.01, Fisher exact test). 54.5% (6/11) of moderate PIH and 55.6% (10/18) of severe PIH had VSMC proliferation. This was only 10.0% (2/20) in normotensive pregnancy. It was significantly lower than those of moderate and severe PIH (P < 0.05, P < 0.005, Fisher exact test). In PIH cases the VSMC proliferation in uterine spiral arteries was correlated with higher c-myc expression (chi-square test, P = 0.0093). CONCLUSION: c-myc expression is higher in VSMC of uterine spiral arteries in PIH. VSMC Proloferates obviously in uterine spiral arteries of PIH cases. VSMC proliferation in PIH may be associated with c-myc expression. PMID- 11775890 TI - [Serum lipoprotein(a) in woman with pregnancy induced hypertension]. AB - OBJECTIVE: To examine lipoprotein(a) level in woman with Pregnancy induced hypertension (PIH) to elucidate the effect of it on the pathogenesis of the disease. METHODS: Serum lipoprotein (a) total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels were measured in 20 normal pregnant woman (control group) and 32 pregnant woman with PIH (PIH group). The PIH group was further divided into the following subgroup: mild, moderate, and severe PIH. We used a transmission turbidimetry method to measure serum lipoprotein(a). RESULTS: (1) The serum lipoprotein (a) levels were higher in PIH group than that in control group (228 +/- 187 mg/L vs 106 +/- 93 mg/L). (2) The serum lipoprotein (a) levels were higher in all PIH subgroups than that in control. (3) The serum levels of TC, TG, LDL-C in the PIH group were higher than those in control, while the level of HDL-C in the PIH group was lower than that in control (0.98 +/- 0.16 mmol/L vs 1.09 +/- 0.17 mmol/L). CONCLUSIONS: This study has demonstrated that lipoprotein (a) levels are elevated in pregnant woman with PIH and associated with severity of the disease. It may involved in the pathogenesis of PIH. PMID- 11775891 TI - [A study on the relationship between serum free alpha-subunit of human chorionic gonadotropin and pregnancy induced hypertension]. AB - OBJECTIVE: To determine the correlation of free alpha subunit of human chorionic gonadotropin (F alpha-hCG) with pregnancy induced hypertension(PIH), and to observe the immunohistochemical expression of alpha-hCG in placentae from PIH. METHODS: Serum was obtained from 66 successive pregnant women diagnosed with PIH (5 mild, 8 middle and 53 severe) at 21-43 weeks' gestation. A group of 30 non PIH gravid women were used as controls. The serum was assayed for F alpha-hCG by monoclonal technology and human prolactin was assayed for correcting the blood contraction. Immunolocalization and the intensity of the immunohistochemical stained in the placentae from 13 PIH and 13 normal pregnancies. RESULTS: Significant difference was noted between the two groups mean of F alpha-hCG (the control group VS PIH group was 528 +/- 421 IU/L VS 222 +/- 129 IU/L, P < 0.001); no significant between two groups of hPL. The mean value of F alpha-hCG of severe PIH revealed significantly higher than the mild and moderate (569 +/- 455 IU/L VS 363 +/- 159 IU/L, P < 0.01); The leve of F alpha-hCG in group of proteinuria > or = +++ was higher than that of proteinuria < +++ (598 +/- 474 IU/L VS 425 +/- 291 IU/L, P > 0.05). The intensity of alpha-hCG immunostaining in syncytiotrophoblast was significantly increased in 13 PIH compared with the control group (the strong positive rate 10/13 VS 3/13 P < 0.025). CONCLUSIONS: The level of F alpha-hCG are significantly higher in PIH compared with controls. The more severe the higher level of F alpha-hCG is in PIH. The higher level of alpha-hCG has the basement of placentae pathology. PMID- 11775893 TI - [Analysis on maternal deaths of cesarean section in Shanghai]. AB - OBJECTIVE: To analyze the causes of maternal deaths of cesarean section and the potential risks of it. METHODS: A retrospective study on maternal deaths of cesarean section from 1978 to 1997 was carried out. RESULTS: (1) The rate of cesarean section in 1978-1987 was 15.55% (258,158/1,659,892), which was significantly lower than that of 29.39% (365,376/1,243,337) in 1988-1997 (P < 0.01). (2) During the 20 years there were 430 cases of maternal deaths in Shanghai. Among them, 150 cases were maternal death after cesarean section which accounted for 34.88%. (3) Maternal mortality rate of cesarean section cases was 24.05/10(5)(150/623,534) which significantly higher (P < 0.01) than that of vaginal delivery, 12.28/10(5)(280/2,279,695). The relative risk of maternal deaths in cesarean section group increased when the cesarean section rate was over 30.00%. (4) The rank order of maternal deaths of cesarean section was as follows: PIH (pregnancy induced hypertension), Cardiac diseases, embolisms, haemorrhage, hepatic diseases, and infections. (5) The relative risk of PIH death either for cesarean section or for vaginal delivery was significantly decreased in 1988-1997, compared to the former 10 years. (6) Of 150 cases of maternal deaths of cesarean section, 43 cases (28.67%) were related to the cesarean section with embolism ranking the first, haemorrage the second and infection the third. CONCLUSIONS: In order to reduce maternal mortality of cesarean section, it is important to pay attention to (1) the prevention and treatment of PIH, heart diseases and embolisms, (2) the indications of cesarean section, (3) improvement of the quality of cesarean section, and (4) pre- and post-operational management. PMID- 11775892 TI - [The effect of Nifedipine on postpartum blood loss in patients with pregnancy induced hypertension]. AB - OBJECTIVE: To determine the efficacy of Nifedipine on postpartum blood Loss in patients with Pregnancy Induced Hypertension (PIH). METHODS: 64 cases of PIH were randomly divided into study group (n = 32) and control group (n = 32). Before labor Nifedipine 10 mg-20 mg was given three time daily for all cases. In study group Nifedipine was taken orally every 6 hours during the labor course until the end of second stage. In control group Nifedipine was not given in the labor stages. The postpartum blood loss was collected and measured carefully within 2 hours after delivery. RESULTS: The amount of pastpartum hemorrhage was (359.1 +/- 136.6) ml in study group which was significantly higher than that of control group (268.5 +/- 110.7) ml P < 0.01. The postpartum hemorrhage rate in study and control group was 43.75% and 18.75% respectively. The difference was statistically significant (P < 0.05). CONCLUSION: During labor using Nifedipine for PIH cases can increase the amount of postpartum blood loss and rate of postpartum hemorrnage. PMID- 11775894 TI - [Obstetrical outcome of pregnancy on in vitro fertilization and embryo transfer 128 cases analysis]. AB - OBJECTIVE: To evaluate the obstetrical outcome of in vitro fertilization and embryo transfer (IVF-ET) pregnancy. METHODS: This study compared the obstetrical outcome of 128 cases of IVF-ET pregnancy with that of 11,372 natural pregnancies as control group. RESULTS: There were 20.3%(26/128) multiple pregnancy, 20.3%(26/128) premature birth, 14.8%(19/128) pregnancy induced hypertension, 25.5%(41/161) small for gestational age, 88.3% (113/128) cesarean section rate and 31.1@1000(5/161) perinatal mortality in the IVF-ET group. However, these data in the control group were 3.3%(380/11,372), 1.0%(119/11,372), 7.6%(863/11,372), 3.6%(416/11,492), 34.7%(3,946/11,372) and 8.9@1000 (102/11,492), respectively. CONCLUSION: The incidence of obstetrical complications was significantly higher in IVF-ET pregnancy. Multiple pregnancy is a high risk factor. PMID- 11775895 TI - [Application of high frequency radiosurgical knife in the treatment of cervical diseases]. AB - OBJECTIVE: To investigate the indication, resection scope of loop electrosurgical excision procedure (LEEP) and pathological characteristics. METHODS: 176 cases with abnormal cytological and colposcopical findings, including cervical intraepithelial neoplasia (CIN) and atypical squamous cells of undermined significance (ASCUS), were studied. Conization of cervix was performed in 63 cases of > or = CIN2, of which 33 cases with LEEP and 30 by traditional electrosurgical knife (TEK) as controls. Cervical biopsy was performed in 113 cases of CIN1 and ASCUS, of which 60 cases by LEEP and 53 by cervical biopsy forceps (CBF) as controls. RESULTS: Three months after conization of cervix the cytological persistent rate of disease was 6.1% in LEEP group and 6.7% in TEK group (P > 0.05). The operation duration of LEEP is (5.0 +/- 0.5) min, and is much shorter than TEK [(15.0 +/- 0.4) min]. The bleeding and recovery time of the cervix are also shorter (P < 0.01). Three months after cervical biopsy the cytological persistent rate of diseases was only 1.7% in LEEP group, significantly less than that in CBF group (35.8%). CONCLUSION: LEEP is indicated to conization of cervix of CIN2-3 and cervical biopsy of CIN1 and ASCUS. It is safe and time-saving. The optimal depth of cervical conization and biopsy was 7 mm and 4 mm respectively in the cervix, and 15 mm and 4 mm respectively in the cervical tube. It can offer intact sample for pathological diagnosis, and has special value for detecting cervical microinvasive carcinoma and local minor carcinoma. PMID- 11775896 TI - [Effects of ovulation induction therapies on endometrial integrin alpha v beta 3 expression in patients with polycystic ovarian syndrome related infertility]. AB - OBJECTIVE: To study the endometrial integrins alpha v beta 3 expressions during mid-luteal(ML) phase in polycystic ovarian syndrome (PCOS) related infertile patients receiving ovulation induction therapies. METHODS: Immunohistochemical methods using monoclonal antibody against integrins alpha v beta 3 were performed on endometrium of ML phase obtained from 22 normal subjects and 40 PCOS related anovulatory patients who underwent ovulation induction therapy by one of the following regimens: clomiphene citrate (CC) + human chorionicgonadotropin (hCG), CC + human menopausal gonadotropin (hMG) + hCG, or gonadotropin-releasing hormone agonist + hMG + hCG. RESULTS: The expressions of endometrial integrin alpha v beta 3 during ML phase in GnRHa + hMG + hMG + hCG cycles were similar with those in normal natural cycles, but were weaker in CC + hCG, CC + hMG + hCG cycles as compared with controls. CONCLUSION: CC + hCG, CC + hMG + hCG regimens may induce decline of endometrial receptivity in ML phase. PMID- 11775897 TI - [Evaluation of tumor necrosis factor-alpha and interleukin-6 levels in serum and peritoneal fluid of patients with endometriosis]. AB - OBJECTIVES: To evaluate the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) before and after conservative laparoscopic surgery in patients with endometriosis. METHODS: The TNF-alpha and IL-6 levels in serum and peritoneal fluid of 20 endometriotic patients and 10 control patients were determined by radioimmunoassay. RESULTS: Significant parallel relationship existed between the stage of endometriosis and the TNF-alpha and IL-6 levels in serum and peritoneal fluid in endometriosis patients (r values: serum: 0.80, 0.52; peritoneal fluid: 0.79, 0.49, P < 0.05). After clearance of endometriosis foci with laparoscopic conservative surgery, the TNF-alpha and IL-6 levels decreased significantly. CONCLUSION: Measuring TNF-alpha and IL-6 level may have important value in postoperative follow-up, surveillance and evaluation of the effectiveness of surgery. PMID- 11775898 TI - [Study on relationship between endometrium laminin expression and irregular uterine bleeding in Norplant users]. AB - OBJECTIVE: To investigate the relationship between endometrium laminin (LN) expression and irregular uterine bleeding in Norplant users. METHODS: Eighteen endomerium samples obtained during day 10-14th from Norlant users for 1/2, 1 or > 2 years respectively with irregular bleeding were studied morphologically and immunohistochemically for LN expression. Six normal proliferative endometria and 18 connterpacts with regular bleeding were used as control. RESULTS: In Norplant users, endometrial glands decreased in numbers and asynchromized in appearance. The LN expression on basal lamina of glandular epithelium and vascular endothelium was lower in those with irregular bleeding as compared with regular bleeders (P < 0.05). CONCLUSION: The decline of LN expression may related to irregular bleeding in Norplant users. PMID- 11775899 TI - [Influence of estrogen on the epithelial ovarian cancer cell lines in vitro]. AB - OBJECTIVE: To study the effect of 17-beta estradiol on the growth of the epithelial ovarian carcinoma cell lines in vitro. METHODS: The proliferative capacity of the ovarian carcinoma cell lines CAOV3 and OVCAR3 in the culture medium with 17-beta estradiol was evaluated by the means of the mircoculture tetrazolium assay (MTT) and cell kinetics was analyzed by flow cytometry (FCM). The expression of estrogen receptor (ER) of the two cell lines was examined by the immunohistochemical staining. RESULTS: The growth of both two epithelial ovarian cancer cell lines was slightly inhibited by 17-beta estradiol (0.25-5.00 nmol/L), and the inhibitive rate was 6.3%-36.0%. FCM showed that the kinetics of the two cell lines were obviously changed. Comparing with the kinetics of CAOV3 without estradiol, the cell rate of Stage G0/G1 of CAOV3 with estradiol decreased from 55.0% to 19.0%-30.0%, cell rate of Stage S increased from 30.0% to 52.0%, cell rate of Stage G2/M increased from 14.0% to 17.0%-28.0%; In OVCAR3, cell rate of Stage C2/M decreased from 37% to 22.0%-30.0%, cell rate of Stage S increased from 31.0% to 38.0%-51.0%, cell rate of Stage C0/G1 did not changed much (cell rate without estradiol was 32.0%, while cell rate with estradiol 29.0%-31.0%). Estrogen receptors of the two cell lines were positive and not changed after cultured in the medium with 17-beta estradiol. CONCLUSION: The proliferate capacity of the two epithelial ovarian cancer cell lines CAOV3 and OVCAR3 can be inhibited by the estrogen (0.25-5.00 nmol/L), possibly through the change of the tumor cell kinetics. PMID- 11775900 TI - [Relationship between serum epidermal growth factor and uterine leiomyoma]. AB - OBJECTIVE: To study the effects of epidermal growth factor (EGF) on uterine leiomyoma and the relationship of EGF and estrogen, progesterone. METHODS: Fourty patients with uterine leiomyoma and twenty normal women were studied. Serum EGF level was determined by radioimumunoassay, estradiol (E2) and progesterone (P) levels were measured by enzyme marked monoclonal antibody assay. RESULTS: Serum EGF, E2 and P levels in observed group were significantly higher than those in control group during secretive phase (P < 0.005). The serum EGF level in observed group during prolifrative phase was significantly higher than that of secretive phase (P < 0.05). The serum EGF level increased while uterus enlarged; EGF wasn't related to E2(r = 0.25, P > 0.05) and was related to P (r = 0.71, P < 0.005). The EGF level was the highest when E2 and P both increased. CONCLUSION: EGF has the effect on growth of uterine leiomyoma. It is possible that EGF secretion can be stimulated by E2 and the effect of P is stronger than E2. PMID- 11775901 TI - [Some problems of diagnosis and treatment on endometrial neoplasms]. PMID- 11775902 TI - [Place of value of pelvic lymphadenectomy for treatment of endometrial neoplasms]. AB - OBJECTIVE: To explore the therapeutic value of pelvic lymphadenectomy for endometrial carcinoma. METHODS: One hundred and four cases undergoing pelvic lymphadenectomy were analyzed. Comparisons were carried out between various clinicopathologic factors and incidence of positive node, between 5 years survival rate with pelvic lymphadenectomy and that without pelvic lymphadenectomy. RESULTS: Four point four per cent case with positive node was found in clinical stage I cases. Positive node rate increased with deep myoinvasion and G3, accounting for 37.3% and 37.8% respectively. For clinical stage I and stage II cases, the 5 year survival rate of positive node and negative node was 38.9% and 74.2% respectively, with significant difference (P < 0.005). No significant difference was found between cases with pelvic lymphadenectomy and those without pelvic lymphadenectomy (P > 0.05) in pathologic stage I and stage II cases. CONCLUSIONS: Positive pelvic node is an important prognostic factor in endometrial carcinoma. Pelvic lymphadenectomy can not improve prognosis in early stage patients with endometrial carcinoma. It is not necessary to perform pelvic lymphadenectomy for stage I case, because of low incidence of positive node. PMID- 11775903 TI - [Value of fractional curettage of prehysterectomy in endometrial neoplasms]. AB - OBJECTIVE: To evaluate the value of fractional curettage in the histologic type, histologic grade and cervical involvement of the endometrial carcinoma. METHODS: A total of 691 cases of endometrial carcinoma in fractional curettage specimen were analyzed retrospectively, patients with no carcinoma postoperatively in the removed uterus were excluded from the study. Those endocervical curettages with adenocarcinoma according the histologic relationship between tumor tissue and endocervical tissue were divided into 4 main groups. RESULTS: (1) The inaccurate rate of histologic type in prehysterectomy curettage was 8.83% (61/691). About a half poorly differentiated adenocarcinomas were undergraded in the prehysterectomy curettage. (2) In 691 cases of endometrial carcinomas, 159 (23.01%) cases were determinated cervical involvement by tumor in the hysterectomy specimen, of which 88 cases had tumor tissue in the prehysterectomic curettage. In a variety of histologic appearances of endocervical curettage, the ratio of cervical involvement by tumor in hysterectomy was respectively group I 30.30% (10/33), group II 9 cases (9/9), group III 100.00% (40/40), group IV 46.88% (29/63), those without tumor tissue in the endocervical curettage 12.68% (71/560). CONCLUSIONS: (1) The reliability of histologic type of endometrial carcinoma based on the findings of the fractional curettage specimen in related to the tumor type. The diagnosis of poorly differentiated adenocarcinomas in the prehysterectomy specimen is limited. (2) Determinating the presence or absence of cervical involvement can't only depend upon the endocervical curettage with or without tumor tissue. It is suggested that those endocervical curettage with tumor tissue be divided into 4 main groups according the histologic relationship between tumor tissue and endocervical tissue, group II and group III are good predictors of cervical involvement by tumor. PMID- 11775904 TI - [Recurrence, metastasis and complications of stage I and II endometrial neoplasms treated by different therapeutic modalities]. AB - OBJECTIVE: To make an approach to the relationship between recurrence, metastasis and complication of stage I and II endometrial carcinoma treated by 4 different therapeutic modalities. METHODS: To compare the rates of recurrence, metastasis and complication in 4 treatment groups (surgery, full-dose preoperative intracavitary irradiation, non-full dose preoperative intracavitary irradiation and radiation alone). RESULTS: Recurrence and metastasis in surgery, full-dose preoperative intracavitary irradiation, non full-dose preoperative intracavitary and radiotherapy alone groups were 19.8%, 8.1%, 22.2% and 34.6%, respectively. The recurrent rates of vaginal stump were 6.2%, 1.6%, 11.1% and 11.5%, respectively. The rates of proctitis and cystitis in full dose preoperative intracavitary irradiation group were 3.2% and 3.2%, 2.8 and 0.0% in non-full dose preoperative intracavitay irradiation group, and 0.0% and 3.8% in radiotherapy alone group. CONCLUSIONS: The rates of recurrence and metastasis in full-dose preoperative intracavitary irradiation group were the lowest compared with other groups and incidence of complication was also low. This therapeutic method is the optimal choice for the treatment of endometrial carcinoma with stage I and II. PMID- 11775905 TI - [Microsatellite instability in endometrial neoplasms correlation with clinicopathologic parameters and estrogen receptor or progesterone receptor status]. AB - OBJECTIVE: To assess the prevalence of microsatellite instability in a series of endometrial carcinomas as well as to define the clinicopathologic features and estrogen receptor (ER) and progesterone receptor (PR) status associated with microsatellite instability (MI). METHODS: We examined 40 cases for replication error (RER) using polymerase chain reaction, polyacrylamide gel electrophoresis and silver stain at 8 microsatellite loci. Immunohistochemical staining of 27 paraffin sections was performed using antibodies to ER and PR. Finally, MI was compared with the clinicopathologic characteristics as well as ER and PR status. RESULTS: MI was observed in 9 (23%) at two or more loci, which is defined as RER positive phenotype. The 9 RER positive cases were all endometrioid type. Four non endometrioid tumors failed to show MI in any locus. RER positive phenotype was more frequent in poorly differentiated (50%) than in well differentiated tumors (15%). We found no significant correlation of RER with stage and depth of invasion. Of 27 carcinomas, 19 (70%) showed homogeneous positive staining for ER and PR. ER and PR positive staining occured more frequently in RER negative endometrioid cancers than in RER positive cases. CONCLUSIONS: MI is one of the molecular mechanisms of a subset of endometrial carcinomas. Its frequency is associated with tumor grade, histological type and ER or PR status. PMID- 11775906 TI - [A clinical prospective study on maternal-fetal transfusion transmitted virus infection]. AB - OBJECTIVE: To observe the transfusion transmitted virus (TTV) infection rate in gravidas and parturients, and explore the route of maternal-fetal transmission. METHODS: TTV infection was detected by nest-polymerase chain reaction (n-PCR) in the serum of 60 healthy gravidas and parturientes. Once parturient infection was identified, the latices and the umbilical blood were examined for TTV infection as well. Meanwhile, a group of non-pregnant healthy women was tested as control. RESULTS: The infection rate of observation group was 28.33%, while in the control group it was 7.57%. The difference of the two groups was significant (P < 0.001). Of the TTV positive parturientes, TTV infection rate of their latices was 27.27%, but none of the umbilical blood samples showed TTV positive. CONCLUSIONS: The TTV infection rate of gravidas and parturientes is higher than that of non-pregnant healthy women. TTV can infect newborns through latices, however, there is no vertical maternal-fetal transmission. PMID- 11775907 TI - [Endothelial dysfunction and injury of placental and umbilical vessels in pregnancy-induced hypertension is associated with tumor necrosis factor]. AB - OBJECTIVE: To investigate the relation between endothelial dysfunction and injury of placental and umbilical vessels in pregnancy-induced hypertension (PIH) and tumor necrosis factor (TNF). METHODS: The concentration of plasma TNF, endothelin (ET) and nitric oxide (NO) in PIH women and normal pregnant women (control group) were measured. The ultrastructure of placenta and umbilical vein endothelial cells in PIH and normal pregnant women was observed. The ultrastructure of endothelial cells in culture with TNF (400 u/ml) was also observed. RESULTS: Maternal plasma TNF and ET levels in PIH patients were (2.27 +/- 0.42) micrograms/L and (73.31 +/- 9.98) ng/L, respectively, higher than that in the control [TNF and ET lever were (1.72 +/- 0.25) micrograms/L and (2.32 +/- 10.44) ng/L, respectively]. NO level in PIH patients was (104.93 +/- 20.54) mumol/L, lower than that in the control [NO lever was (138.25 +/- 22.16) mumol/L] (P < 0.05). The ultrastructure of placental and umbilical vascular endothelial cells in moderate and severe PIH patients revealed injured. Similar injury was observed in endothelial cells in culture with TNF. CONCLUSIONS: TNF can induce the endothelial cells dysfunction and injury. It may be involved the pathogenesis of PIH. PMID- 11775908 TI - [Inhibitory effects of ligustrazine on the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 in human umbilical vein endothelial cells induced by preeclamptic plasma]. AB - OBJECTIVE: To determine whether plasma from preeclamptic women induces expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cultured endothelial cells, and the effects of ligustrazine (LTZ) on the expression of ICAM-1, VCAM-1. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated by collagenase mixed with trypsin. LTZ was added to HUVEC monolayers grown to confluency on 96-well microplates for 30 minutes. Then HUVEC were incubated with medium containing 20% plasma (volume/volume) either from women with preeclampsia or normotensive pregnancy or nonpregnant women. ICAM-1, VCAM-1 expression was determined after 16 hours of exposure by an enzyme-linked immunosorbent assay (ELISA) technique performed on the cell monolayer. RESULTS: There was a statistically significant increase in ICAM-1, VCAM-1 expression in the endothelial cells exposed to preeclamptic and nonpregnant plasma compared with those exposed to normotensive plasma. Pretreatment with LTZ could reduce the expression of ICAM-1 exposed to preeclamptic plasma, and reduce the expression of VCAM-1 exposed to any of the three sources of plasma. CONCLUSIONS: Preeclamptic plasma induces ICAM-1 and VCAM 1 expression in HUVEC in vitro. Ligustrazine may inhibit the upregulation effects of ICAM-1 and VCAM-1 expression induced by preeclamptic plasma. PMID- 11775909 TI - [Effect of hormone replacement therapy on coagulation function in postmenopausal women]. AB - OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on coagulation function in postmenopausal women. METHODS: Fifty-two postmenopausal women were divided into three groups; placebo group (10 cases), estrogen group (19 cases) and estrogen plus progesterone group (23 cases). Twenty healthy premenopausal women served as control group. The coagulation parameters were determined before and 3, 6 months after initiation of HRT. RESULTS: The levels of fibrinogen and protein S in postmenopausal women were significantly higher than those in the control group. There was no difference in coagulation parameters before and after placebo administration. After 3-month HRT, the fibrinogen levels in estrogen group and estrogen plus progesterone group significantly decreased and further decreased after 6-month HRT, as compared with before HRT. A significant decrease was also noted in protein S in both groups after 3 month HRT, but returned closely to baseline after 6-month HRT. There was no significant difference in coagulation parameters between estrogen group and estrogen plus progesterone group either before or after HRT. CONCLUSION: HRT significantly decrease the levels of fibrinogen in postmenopausal women. PMID- 11775910 TI - [Pelvic exenteration of advanced gynecological malignacies: a report of 18 cases]. AB - OBJECTIVE: To investigate the role of pelvic exenteration in the treatment of advanced gynecological malignances. METHODS: Eighteen patients with cervical cancer in 8, vulvar cancer in 8, and vaginal cancer in 2, who underwent pelvic exenteration at the Cancer Hospital of Shanghai Medical University between 1970 and 1990 were retrospectively analyzed. RESULT: Median age was 52 years (range 27 65). One woman received surgery of total pelvic exenteration, 10 anterior and 7 posterior exenteration. The 3,5-year survival rates were 72%, 50%, respectively. Postoperative morbidity was 16%, and the surgical mortality was 0%. Bowel obstruction occurred in 2 of 18 cases, one of them was treated surgically. CONCLUSIONS: (1) Patients with advanced central type pelvic neoplasms can be successfully treated with exenteration; (2) The patients should be properly selected prior to and in operation, and the procedures must be performed specifically, particularly in exploration stage. PMID- 11775911 TI - [Expression of mismatch repair gene hMSH2 in human malignant ovarian tumors and its clinical significance]. AB - OBJECTIVES: To study the expression of hMSH2 gene in human malignant ovarian tumor and its relationship to clinicopathological characteristics. METHODS: The expression of hMSH2 gene in 42 patients with malignant ovarian tumor was detected by immunohistochemistry streptomycin peroxidel method using monoclonal antibody to hMSH2 protein. RESULTS: hMSH2 expression was observed in the 26 of 42 malignant ovarian tumors (62%), more frequently present in serous and mucinous adenocarcinoma (80%, 80%) than in endometrioid adenocarcinoma and malignant germinal tumors (1/6, 1/6) (P < 0.05). It was significantly higher in high grade than in low grade (P < 0.05), and the reduced expression of hMSH2 was also significantly more often in lymphnodes metastasized cases. Statistical analysis indicated that hMSH2 expression wasn't related to the stage of the tumors. CONCLUSIONS: These results suggest that the abnormal expression of hMSH2 might be involved in the carcinogenesis process and progression of malignant tumor, and that the loss of the hMSH2 protein expression might be a useful predictor of early diagnosis and prognosis of malignant ovarian tumor. PMID- 11775912 TI - [Pneumonia in the antibiotic era]. PMID- 11775913 TI - [Laboratory and clinical investigation on lower respiratory tract infection by Haemophilus influenzae]. AB - OBJECTIVE: To improve the positive rate of Hi isolation and to study the epidemiology, antibiotic sensitivity and clinical characteristics of the lower respiratory tract infection by Hi. METHODS: Modified Columbia chocolate agar(ICCA) was compared with blood agar staphy stick (BASS) for the primary isolation of Hi from sputa. The sensitivities of 20 antibiotics to Hi were determined in vitro by KB method and MICs of 12 antibiotics were determined by broth microdilution method. The clinical characteristics of 92 cases with lower respiratory tract infection by Hi were analyzed. RESULTS: The isolation rate of Hi by ICCA was 20%, which was higher than 13% of BASS(P < 0.01). The third generation cephalosporins and the quinolones were most active against Hi. The resistant rate against Hi of ampicillin was 21%, however, that of the third generation cephalosporins was 45%-49%. 67(73%) of 92 cases were bronchopneumonia. CONCLUSIONS: The isolation rate of Hi could be improved by ICCA. The clinical characteristic of lower respiratory tract infection by Hi was not specific. There has been a steady increase of antibiotic resistance during these years. PMID- 11775914 TI - [Analysis of clinical characteristics and drug sensitivity tests of lower respiratory tract infection by Xanthomonas maltophilia]. AB - OBJECTIVE: To analyse the clinical characteristics of lower respiratory tract infection caused by Xanthomonas maltophilia and to investigate the antibiotic sensitivity of Xanthomonas maltophilia strains. METHODS: Retrospective study of the clinical data of 54 cases with lower respiratory tract infection by Xanthomonas maltophilia, including risk factors of morbidity, clinical symptoms and signs, X-ray findings, blood routine test, treatment and prognosis. Drug sensitivity against strains of Xanthomonas maltophilia by K-B method was studied. RESULTS: There were 39 males and 15 females, the mean age being 51 +/- 17 years. 87% of the cases had underlying diseases, most of which were COPD complicated by respiratory failure. 57% of the cases were immunocompromised. 39% of the cases were in ICU or CCU. 54% of the cases accepted invasive treatments, and 93% of the cases were given broad-spectrum antibiotics. Clinical manifestations include chill (72%), fever (80%), cough (94%) and expectoration (91%). The chest X-ray revealed infiltration in lower lobes of both lungs. 16 cases had consolidations, and 11 cases were complicated with pleural effusions. The drug sensitivity test in vitro showed that these strains were multiresistant to commonly used antibiotics, and drugs whose sensitive rate were over 50% included SMZco, ceftazidine, and timentin. CONCLUSIONS: The lower respiratory tract infections caused by Xanthomonas maltophilia develop at patients with various underlying diseases, especially in the immunocompromised patients. Risk factors of morbidity were: patients in ICU or CCU, acceptance of invasive treatment and inappropriate use of broad-spectrum antibiotics. Clinical manifestations include severely toxic symptoms and some cases had pulmonary consolidations and pleural effusions. PMID- 11775915 TI - [Study on combined detection of M. genitalium, M. pneumoniae and C. pneumonia by nested polymerase chain reaction in respiratory tract infections in pediatric patients]. AB - OBJECTIVE: To study the respiratory tract infections by Mg, M. genitalium (Mpn), Cpn, and co-infections by these agents in pediatric patients. METHODS: Mg DNA, Mpn DNA and Cpn DNA were detected in respiratory tract specimens obtained by throat swab from 231 children by the nested polymerase chain reaction (PCR) technique. DNA sequencings were detected and analysed between every two positive specimens of Mg and Cpn and typical strains. RESULTS: Positive rates of Mg DNA, Mpn DNA and Cpn DNA by nested PCR in 231 children were 22.5%, 30.7% and 32.9%. The Positive rates of co-infection were 5.2% (Mg and Mpn), 2.6% (Mg and Cpn), 10.8% (Mpn and Cpn) and 8.7% (Mg and Mpn and Cpn). There was only one base mutation in 1 Mg DNA. Other DNA sequencings were same as those from model strains. The homogeneity was 99.8%. CONCLUSIONS: Mg could be one of the pathogens in respiratory tract infections in pediatric patients. There exists co-infection by Mg, Mpn and Cpn. PMID- 11775916 TI - [Mite-induced interleukin-5 and interleukin-4 expressions in peripheral blood mononuclear cells from asthmatic children with respiratory syncytial virus infection]. AB - OBJECTIVE: To investigate the effects of respiratory syncytial virus(RSV) infection on mite-induced interleukin-5 and interleukin-4 expressions in cultures of PBMC from asthmatic children and their correlation with asthmatic symptoms. METHODS: IL-5 and IL-4 expressions in mite (D. Pteronyssinus)-stimulated PBMC were assessed ex vivo by ELISA and reverse transcription-polymerase chain reaction (RT-PCR) in 16 allergic asthmatic children with RSV infection(A) and 14 patients without RSV infection(B), as well as 10 normal controls(C) (5.1 +/- 2.4 yrs). Meanwhile their correlation with serum ECP or current wheezing was analysed in patients after RSV infection. RESULTS: (1) Stimulation of PBMC with mite antigens induced significantly higher IL-4 (34 +/- 24) ng/L vs (8 +/- 5) ng/L, (P < 0.01) and IL-5 (26 +/- 15) ng/L vs (6 +/- 5) ng/L release in allergic patients(B) as compared with healthy controls(C). The release was in a mite dose dependent manner. Meanwhile, IL-5 level in group A (A) was the highest (73 +/- 47) ng/L, P < 0.05 compared with (B)). Similar results were obtained with IL-5 mRNA expressions. (2) Serum ECP level was significantly higher in group A (73 +/- 47) micrograms/L than in group C (18 +/- 12) micrograms/L, P < 0.01. There was a significant correlation between IL-5 release and ECP levels (r = 0.49, P < 0.05). (3) Mite-induced IL-5 release in PBMC was significantly increased in the group with wheezing symptom (71 +/- 40) ng/L compared with the asymptomatic group (34 +/- 29) ng/L, (P < 0.05). CONCLUSIONS: Our findings indicated that during RSV infection, mite-induced IL-5 expression in PBMC of asthmatic children was up regulated, which may enhance activation of eosinophils and precipitate or exacerbate asthma symptoms. PMID- 11775917 TI - [mRNA expression of basic fibroblast growth factor in the pulmonary tissues from rats repeatedly infected with mycoplasma pneumoniae]. AB - OBJECTIVE: To investigate changes in mRNA expression of basic fibroblast growth factor (bFGF) in pulmonary tissues from rats repeatedly infected with Mycoplasma pneumoniae (MP). METHODS: Rats were infected with MP for 9 times during a period of 24 weeks by ultrasonic nebulizing inhalation to establish animal models of chronic pulmonary MP infection. In situ hybridization was performed with bFGF cDNA probe and results were quantitatively analysed to measure the changes of bFGF mRNA expression in lung tissues. RESULTS: (1) MP polymerase chain reaction (PCR) tests showed positive results in the bronchoalveolar lavage fluid (BALF) from MP infected animals (n = 4) while results were negative for BALF from the control rats (n = 4) and rats infected with MP but treated with erythromycin (n = 4). Bacterial cultures of the bronchial and the lung tissues were negative in all three groups. Observation with transmission electron microscope showed that interalveolar septa were widened with increased amount of collagen in the MP infected rats while there were no obvious abnormalities in the other two groups. (2) Positive expression of bFGF mRNA were found in alveolar walls of MP infected rats. No expression of bFGF mRNA was found in control animals. In the rats infected with MP but treated with erythromycin positive expression of bFGF mRNA was found to be scarcely distributed in alveolar walls. Quantitative analysis showed that the optical densities of bFGF mRNA expression were 41.32 +/- 10.44 in the MP infected rats (n = 4), which were significantly higher than those in the control group (0.30 +/- 0.13, n = 4, P < 0.01) and those in the MP infected and erythromycin treated rats (6.03 +/- 2.41, n = 4, P < 0.01). CONCLUSIONS: Repeated pulmonary infection with MP can lead to up-regulation of bFGF mRNA expression, which suggests that bFGF might play a role in the pathogenesis of pulmonary interstitial fibrosis after repeated MP infection. PMID- 11775918 TI - [Detection and significance of interleukin-16 in sputa from patients with bronchial asthma]. AB - OBJECTIVE: To explore the significance of in the terleukin-16 (IL-16) in pathogenesis of bronchial asthma. METHODS: Induced sputum samples were obtained from 12 allergic asthmatics, 8 non-allergic asthmatics, 10 non-asthma allergic and 10 non-asthma non-allergic normal subjects. ELISA was used to determine the concentrations of IL-16 in sputum, and CD4+ T cells and activated eosinophils (EG2 cells) in sputum were detected by immunostaining. RESULTS: IL-16 levels in both allergic and non-allergic asthmatics were much higher than those in non asthma allergic or non-asthma non-allergic normal subjects. Effective anti-asthma treatment led to a significant decrease in IL-16 levels in patients with acute asthma. It was also found that the percentages of CD4+ and EG2 cells were all positively correlated to IL-16 levels. CONCLUSIONS: IL-16 is involved in the asthmatic process by recruiting CD4+ T cells and thus plays an important role in CD4+ cell-dependent eosinophilic inflammation in asthmatic airways. PMID- 11775919 TI - [Correlation of eosinophil apoptosis with interleukin 5 mRNA expression in lung tissues of asthmatic guinea pigs]. AB - OBJECTIVE: To explore the correlation of interleukin 5 mRNA expression with eosinophil apoptosis in lung tissues of asthmatic guinea pigs. METHODS: Guinea pigs were divided into asthma, asthma pretreated with dexamethasone and control groups. Guinea pigs were sensitized by exposure to aerosolized ovalbumin. Twenty four hours after the animals were challenged by aerosolized ovalbumin, the apoptosis percentages of hypodense eosinophils(HEo) and normodense eosinophils(NEo) in bronchoalveolar lavage fluid (BALF), and IL-5 mRNA expression in lung tissues were detected with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique and in situ hybridization. RESULTS: (1) In the asthmatic group, the percentages of HEo and NEo apoptosis were significantly decreased (P < 0.05), and IL-5 mRNA expression was significantly increased as compared with the control (P < 0.01). (2) In the group pretreated with dexamethasone, the apoptosis percentages of HEo and NEo were significantly increased (P < 0.01), and IL-5 mRNA expression was reduced as compared with the asthmatic group (P < 0.01). (3) IL-5 mRNA expression was negatively correlated with apoptosis percentage of HEo (r = -0.491, P < 0.05) and NEo (r = -0.492, P < 0.05). CONCLUSIONS: IL-5 mRNA expression in lung tissues closely correlated with apoptosis percentage of Eos in BALF. Inhibiting the expression of IL-5 mRNA and promoting the apoptosis of Eos in lung tissues may be one of the important mechanisms of glucocorticoids to reduce infiltration of Eos in lung tissues and their therapeutic effect in asthma. PMID- 11775920 TI - [Evidence of increased endogenous carbon monoxide production in asthma]. AB - OBJECTIVE: To investigate the role of carbon monoxide (CO) in the pathogenesis of asthma. METHODS: We examined CO, nitrite and nitrate (NO2[not readable: see text]/NO3[not readable: see text]) and tumor necrosis factor alpha (TNF-alpha) levels in plasma of 26 asthmatic children and 22 matched normal children. At the same time, we examined the plasma and bronchoalveolar lavage fluid (BALF) CO, NO2[not readable: see text]/NO3[not readable: see text] and TNF-alpha levels in guinea-pigs with allergic asthma. RESULTS: Asthmatic children in acute attack stage had increased levels of CO, NO2[not readable: see text]/NO3[not readable: see text] and TNF-alpha in plasma compared with normal control subjects (all P < 0.01), while in stable stage plasma CO and NO2[not readable: see text]/NO3[not readable: see text] reduced to normal levels (both of the P > 0.05), but TNF alpha was still higher than the normal controls (P < 0.01). Guinea-pigs with allergic asthma had increased amounts of CO and TNF-alpha in plasma and CO, NO2[not readable: see text]/NO3[not readable: see text] and TNF-alpha in BALF as compared with normal control subjects (P < 0.05-0.01), but no changes in levels of circulating NO2[not readable: see text]/NO3[not readable: see text] (P > 0.05) were found. There was no difference between glucocorticoid treated asthmatic guinea pigs and normal controls in levels of CO, NO2[not readable: see text]/NO3[not readable: see text], and TNF-alpha. The elevation of plasma CO correlated with elevated NO2[not readable: see text]/NO3[not readable: see text] level in asthmatic children (P < 0.05), so did in the BALF in allergic guinea pigs. CONCLUSIONS: Our present data showed that endogenously produced CO was increased during the course of asthma, which suggested that the role of CO in asthma might worth further study. PMID- 11775921 TI - [Study on anticholinergics for the treatment of high altitude pulmonary edema]. AB - OBJECTIVE: To evaluate the clinical effects and mechanism of anticholinergics in treating high altitude pulmonary edema (HAPE). METHODS: 582 patients with HAPE (in 4700-5260 m) were divided into 2 groups: one group (393 patients) was treated with anticholinergic (Group A), and the other 189 cases were treated with a general therapy without anticholinergic (Grorp B). RESULTS: Compared with Group B, the average admitted days were reduced, the symptom, physical and X-ray signs disappeared more quickly (P < 0.001), the cure rate was raised clearly (P < 0.05) in Group A and the abnormal changes of hemodynamics had been adjusted (P < 0.05, P < 0.01). CONCLUSIONS: Anticholinergic used for HAPE has a rapid and exact curative effect, a slight side effect, and a shorten course of treatment. PMID- 11775922 TI - [CT in diagnosis of tuberculosis of liver and spleen]. AB - OBJECTIVE: To analyze CT findings of hepatospleeno-tuberculosis and to explore the characteristics for diagnosis and differential diagnosis of the disease. METHODS: CT scans were performed in fifteen patients. There were nine men and six women, the age ranging from 18 to 60 years old. All patients were diagnosed clinically, one of which was confirmed by pathology after surgery, two of which were confirmed by pathology through CT-guided biopsy. RESULTS: All cases were concurrent with two or more other tuberculosis. Disseminated milliary, small nodules and small saccular foci were present in livers of 8 cases and spleens of 5, and isolated low dense lesion in liver of 1 case, diffuse calcifications in liver and spleen of another 1. CONCLUSIONS: When disseminated milliary, small nodules and small saccular foci are found by CT in liver or spleen and tuberculous lesions are present in other tissues, diagnosis of liver and/or spleen tuberculosis should be considered. PMID- 11775923 TI - [Clinical analysis of 96 cases with pulmonary disease caused by nontuberculous mycobacteria]. AB - OBJECTIVE: To study the clinical characteristics of nontuberculous mycobacteria (NTM) pulmonary disease. METHODS: Ninety-six out of 173 cases with NTM pulmonary disease diagnosed through identification of mycobacterium strains isolated from 5,592 sputum acid-fast staining positive cases from 1981-1996 were selected, and a retrospective analysis was made. RESULTS: According to Runyon classification, there were 14 cases with M. kansasii and 1 with M. marinum in type I, 4 with M. scrofulsceum in type II, 23 with M. intracellulare or M. avium in type III, 24 with M. chelonae and 30 with M. fortuitumin in type IV. Cases whose courses of disease were more than 10 years accounted for 31%. Main clinical symptoms included cough (78%), expectoration (71%), haemoptysis (58%) and fever (26%). Fifty-seven percent cases in X-ray chest film were seen lesions bilaterally, 42% in one side, 27% in the right and 15% in the left. One percent showed no obvious lesion in X-ray chest film. Excluding one case with incomplete data, the total resistance rate of NTM was 96% in other 95 cases, 93% in type I, 50%, 100% and 100% in type II, III, IV respectively. After antituberculous chemotherapy, sputum negative conversion was seen in 14 of 15 cases with type I NTM, 6 of 23 with type III and 14 of 54 with type IV, while definite data in 4 cases with type II were not available. CONCLUSIONS: NTM pulmonary disease is characterized by long course of disease, nonspecific symptoms, high resistance rate and unsatisfactory therapeutic efficacy. PMID- 11775924 TI - [Effect of pneumothorax on membrane diffusing capacity and pulmonary capillary blood volume]. AB - OBJECTIVE: Investigating the effect of pulmonary membrane diffusing capacity(Dm) and pulmonary capillary blood volume(Vc) on carbon monoxide diffusing capacity (DLCO) in patients with pneumothorax before and after treatment, and clarifying the mechanism of hypoxemia due to pulmonary reexpansion. METHODS: Pulmonary function test, DLCO, Dm, Vc and arterial blood gas analysis were determined in 21 cases of pneumothorax before treatment and one week after pulmonary reexpansion. RESULTS: DLCO, Dm, Vc, partial pressure of arterial oxygen (PaO2), alveolar ventilation volume (VA), percentage of forced expiratory volume in one second to predicted value, and the ratio of dead space ventilation (VD) to tidal volume (VT) [VD/VT] were (64 +/- 4)%, (66 +/- 5)%, (70 +/- 5)%, (83.7 +/- 2.3) mm Hg, (4.4 +/- 0.2) L, (59 +/- 4)%, 0.340 +/- 0.020 respectively before treatment. After pulmonary reexpansion, they respectively were (71 +/- 4)%, (74 +/- 4)%, (80 +/- 6)%, (89.4 +/- 1.5) mm Hg, (5.40 +/- 0.20) L, (79 +/- 4)%, 0.210 +/- 0.010. They were significantly improved after treatment. Except for Dm, they were statistically different. Between Dm, Vc and DLCO, significant positive correlations were found during pneumothorax and one week after pulmonary reexpansion, especially correlation between Dm and DLCO was more apparent. Between Dm and DLCO significant positive correlations (r2 = 0.862, P < 0.0001; r2 = 0.728, P < 0.001) were found in study patients before and after treatment. So were Vc and DLCO (r1 = 0.643, P < 0.01; r2 = 0.52, P < 0.05). The correlation coefficient of Dm was markedly larger than Vc. CONCLUSIONS: The decrease in pulmonary diffusing function is related to Dm and Vc during pneumothorax, while decrease of Dm plays a major role. The hypoxemia is still presented in a period of time after pulmonary reexpansion, which is not related to VA and abnormality of ventilation-perfusion ratio (V/Q). It is chiefly due to unrecovery of Dm. PMID- 11775925 TI - Carers bear burden of home care. PMID- 11775926 TI - The use of oxycodone in cancer-related pain: a literature review. AB - Oxycodone is a semi-synthetic opioid agonist that can be used as an alternative to morphine in controlling cancer pain. It differs from morphine in its biphasic qualities in controlled release (CR) formulation. This review of post-1995 international literature explores the use of oxycodone compared with morphine, as well as titration studies comparing CR formulation against the conventional immediate release (IR) formulation. Most studies involved small numbers and so their results cannot be generalized. Statistical tests were used inappropriately in several of the studies reviewed, which compromises the validity of the findings, but it is important to note that there was broad agreement between researchers. Studies were graded based on research quality criteria of the US Agency for Health Care Policy and Research (United States Department for Health and Human Services, 1993). Conversion ratios and side-effects are discussed and recommendations made for the use of oxycodone in opioid rotation, particularly for patients suffering morphine-induced hallucinations. Several studies also recommend the use of oxycodone in preference to morphine in patients with renal impairment. PMID- 11775927 TI - Developing effective palliative care within a prison setting. AB - A joint report by the UK prison service and the National Health Service (Department of Health (DoH), 1999) suggested that a 'formal partnership' between the two organizations would enhance the health care of people in prison. Through such a partnership it is hoped that prisoners will be able to receive the same level of care as those who are treated within the wider community. Nurses attempting to achieve the goals of palliative care within a prison setting may encounter environmental constraints to their work and may be further deterred by their own lack of specialist knowledge. This article discusses how such problems can be overcome through the professional development of prison nurses. PMID- 11775928 TI - Community palliative care clinical nurse specialists' descriptions of stress in their work. AB - This study analysed the lived experiences of work stress of 21 community palliative care clinical nurse specialists from four centres in urban Essex, UK. Data were collected using an open-ended questionnaire and semi-structured interviews. Three major themes emerged: pressure of workload; relationships with health professionals; and the impact of the sadness of the client group. The pressure of workload was associated with nine sub-themes including staff shortages, client's or professionals' misperceptions of role, changing role, and erosion of normal support systems at work or at home. Relationships with some general practitioners seemed to cause most difficulty and social services seemed to have different priorities and to respond slowly. The impact of the sadness of the client group was only seen in four distinct situations. An overwork stress spiral is described that provides a salutary warning for managers, but also offers interesting solutions. PMID- 11775929 TI - Tending the soul as well as the body: spiritual care in nursing and residential homes. AB - This article reports findings from a study in the UK which investigated the perceptions and practice of spiritual care in care homes for older people. Over 1500 homes were sent a postal questionnaire and a response rate of 42% was achieved. Home managers were found to have a broad understanding of spiritual care, according a spiritual dimension to a range of tasks that were social and emotional in nature. Most managers felt that responsibility for providing spiritual care lay with the home itself, rather than other parties, although concerns were expressed over the ability of some staff to deliver this care. Many homes had input from religious providers via regular services and visiting personnel. There was a perception of a heightened level of spiritual need for dying residents, although it is suggested that physical pain continues to dominate the focus of care at this stage. PMID- 11775930 TI - Malignant bowel obstruction: so much more than symptom control. AB - Malignant bowel obstruction is a life-threatening complication in patients with advanced cancer which has, until recently, required patients to be cared for in medical establishments. The majority of literature examining malignant bowel obstruction discusses medical and surgical care of patients. The nursing dimension of caring for such patients appears to have been rarely explored despite the impact that medical advances have had on nursing care in ensuring that people with a terminal illness are nursed appropriately. Advances in medical management and nursing initiatives now give this group of patients the choice of care setting. This article explores the complexity of malignant bowel obstruction alongside the its medical management, and highlights the challenge of nursing a patient experiencing malignant bowel obstruction as a terminal event. PMID- 11775931 TI - Palliative care in Western Australia: an assessment of information and support needs. AB - Health professionals in rural Western Australia have embraced palliative care, however, to date no information has been available about the issues that face those providing the care. The descriptive study was undertaken to determine what palliative care education and support resources were available to rural health professionals, and to ascertain what further services would be of benefit to their practice. The findings of this study suggests that rural health professionals would welcome increased access to both education and support services when providing palliative care to patients in their communities. Recommendations are made that could enhance the delivery of palliative care education and support to rural Western Australia. PMID- 11775932 TI - Successful management of malignant bowel obstruction. PMID- 11775933 TI - Viral load: small change by sixth day of treatment can often predict poor response. PMID- 11775934 TI - New resistance test combines phenotype and genotype. PMID- 11775935 TI - Protease inhibitors in children: combination therapy reduced death by two thirds. PMID- 11775936 TI - South Africa: activists, physicians sue government to prevent maternal transmission, ask international support. PMID- 11775937 TI - HIV testing 101 (Part 1 of 2). PMID- 11775938 TI - [Application of the fluorescent in situ hybridization on the prenatal diagnosis of the fetal aneuploidy in the uncultured amniocytes]. AB - OBJECTIVE: To study the method and value of fluorescent in situ hybridization (FISH) on the rapid prenatal diagnosis of the fetal aneuploidy in the uncultured amniocytes. METHODS: Amniocentesis was performed in 20 pregnant women of 16-36 gestational weeks with indications of prenatal diagnosis. We performed FISH, respectively, with the biotin labelled chromosome X and 18 centromeric probes and the digoxin labelled chromosome Y centromeric and 21q11 and 13q14-q21 specific probes on the uncultured amniocytes. The slides were observed under the fluorescent microscope and the images were captured by the Applied Imaging System. RESULTS: Normal chromosome number was observed in 19 cases: 10 cases of 46, XX and 9 cases of 46, XY. Aneuploidy was found in 1 case which was 46, XY/47, XXY and proved by G-banding chromosomal on cord blood. CONCLUSION: Fetal aneuploidy could be diagnosed within 24 hours after the amniocentesis by FISH. FISH is a rapid, accurate and reliable method to detect fetal aneuphoidy in uncultured amniocytes. PMID- 11775939 TI - [Changes of selenium concentration and glutathione peroxidase activity in maternal and cord blood in intrahepatic cholestasis of pregnancy]. AB - OBJECTIVE: To investigate the importance of selenium concentration and glutathione peroxidase (GSH-Px) activity in intrahepatic cholestasis of pregnancy (ICP). METHODS: We measured the selenium concentration by a catalytic polorographic method and GSH-Px activity by a 5,5'-dithionbis (2-nitrobenzoic acid) direct method in maternal and cord blood in 30 pregnant women with and without this disease respectively during the last trimester of pregnancy and post partum and in 30 non-pregnant women. RESULTS: Sults (1) The selenium concentration and GSH-Px activity in maternal blood were found to be significantly lower in ICP than in women with normal pregnancies during the last trimester [(0.0389 +/- 0.0090) mg/L, (0.0477 +/- 0.0094) mg/L, P < 0.001] [(59.31 +/- 11.42) U, (68.48 +/- 10.47) U, P < 0.002] and post partum [(0.0463 +/- 0.0092) mg/L, (0.0510 +/- 0.0093) mg/L, P < 0.05] [(68.12 +/- 11.46) U, (72.67 +/ 9.83) U, P < 0.05]. (2) The selenium concentration and GSH-Px activity in cord blood was significantly decreased in ICP than that of normal pregnances [(0.0387 +/- 0.0093) mg/L, (0.0461 +/- 0.0089) mg/L, P < 0.005)] [(57.66 +/- 12.55) U, (67.46 +/- 11.93) U, P < 0.005)] (3) The activity of the selenoenzyme GSH-Px had a significant positive correlation with selenium concentration (P < 0.001). CONCLUSION: The blood selenium deficiency and reduced GSH-Px activity may lead to the formation of free radicals, which could damage the structure and function of hepatocytes and result in ICP. PMID- 11775940 TI - [Detection of the asymptomatic infection by human papillomavirus in pregnant women and neonates]. AB - OBJECTIVE: To investigate the state of human papillomavirus (HPV) infection in similar average-aged pregnant women of different gestational periods, in the puerperium and neonates. METHODS: Polymerase chain reaction (PCR) assay was employed to detect HPV-6, 11, 16 and 18 DNA in 30 pregnant women in the first trimester, 42 in the second and 31 in the third (who were followed up to their puerperium), and 30 non-pregnant women asking for intrauterine device in our out patient clinic were taken as controls. Average age in the four groups showed no significant difference (P > 0.05). Samples from cervical, vaginal exfoliated cells, maternal peripheral blood and nasopharyngeal secretion of the newborns were examined respectively. RESULTS: (1) In the first trimester, HPV-DNA was detected in the cervical, vaginal exfoliated cells of 5 cases and in the maternal peripheral blood of 7 cases. (2) In the second trimester, HPV-DNA was detected in the cervical, vaginal exfoliated cells of 12 cases and in the maternal peripheral blood of 11 cases. (3) In the third trimester, HPV-DNA was detected in the cervical, vaginal exfoliated cells of 23 cases and in the maternal peripheral blood of 18 cases. (4) In the puerperium, HPV-DNA was detected in samples of cervical, vaginal exfoliated cells of 8 cases and maternal peripheral blood of 7 cases. (5) In the control group, HPV-DNA was detected in the cervical, vaginal exfoliated cells of 8 cases and in the maternal peripheral blood of 6 cases. (6) Consecutive examinations were carried out in 31 pregnant women from the third trimester, through labor to 6 weeks of postpartum. HPV-DNA was positive in the cervical, vaginal samples of 17, 21 and 8 cases, respectively, according to the perinatal periods, and in the maternal peripheral blood of 14, 13 and 7 cases, respectively. The result through the above gestational stages was fluctuated in the cervical, vaginal samples of 6 cases and in the maternal peripheral blood of 7 cases. (7) Successive examinations in infants at time of birth, 48-72 h and 6 weeks after birth showed positive HPV-DNA in the nasopharyngeal secretion of 13, 6 cases and 1 case with respect to the examining periods. (8) The positive cases were mainly infected by HPV-16, 18. CONCLUSIONS: (1) Infective rate of HPV is statistically significant in the third trimester, but no significant difference exists among the first trimester, the second trimester, the puerperium or the non pregnancies. (2) Examining consecutively, the HPV positive rate is found to be decreased after delivery, the positive expression of HPV during the gestational periods exhibited fluctuation. (3) Infective rate of HPV in the neonatal nasopharyngeal specimens tends to decrease with time after delivery. PMID- 11775941 TI - [In vitro study of prolactin secretion by ectopic endometrial stromal cells]. AB - OBJECTIVE: To investigate the relationship between prolactin (PRL) secretion by ectopic endometrial stromal cells and elevated PRL concentrations of peritoneal fluid in patients with endometriosis. METHODS: Twelve samples of each ectopic endometrium and normal endometrium were separated and cultured in vitro. After stimulated with progesterone(10(-8) mol/L) for 6 days, PRL levels in the media of cultured stromal cells from both tissue types were measured by enzyme-labeled immunosorbent assay(ELISA). A study of correlation between PRL level in culture supernatant of stromal cells from ectopic endometrium and American Fertility Society (AFS) classification of endometriosis score was performed. The expression of PRL protein of stromal cells from both tissue types were determined by immunocytochemical method. RESULTS: PRL was secreted in similar concentrations by stromal cells from both tissue types. The mean levels of PRL in ectopic and normal endometria were (21.8 +/- 8.0) and (24.5 +/- 7.9) micrograms.L-1.6 d-1 per, respectively (P > 0.05). There is significant positive correlation between PRL secretion by ectopic endometrial stromal cells and the scoring of endometriosis (P < 0.05). There were no significant difference in the immunostaining integral score of PRL between the two groups. CONCLUSION: Production of PRL by ectopic implants of endometriosis is likely to be a contributing factor of the elevated peritoneal fluid PRL in patients with endometriosis. PMID- 11775942 TI - [Expression of major histocompatibility complex-class I antigen on endometrial stroma cells in patients with endometriosis]. AB - OBJECTIVE: To study the possible effect of major histocompatibility complex-class I (MHC-I) antigen on endometrial stromal cells in endometriosis patients. METHODS: The stromal cells of endometrium was separated and cultured in vitro. gamma-interferon (gamma-IFN) was added to modulate the MHC-I antigen level which was assessed by flowcytometry, and the sensitivity of endometrial stromal cells to cytotoxic lymphocytes was examined by methyl thiazolyl tetrazolium (MTT). RESULTS: Our study demonstrated that in vitro cultured stromal cells with significant reduced MHC-I antigen levels showed enhanced susceptibility to lysis (51.28%) mediated by lymphokine-activated killer (LAK) cells, whereas gamma-IFN treated in vitro cultured stromal cells with restored MHC-I antigen levels showed more resistance to lysis (28.64%). CONCLUSIONS: MHC-I antigen on endometrial stromal cells may inhibit the cytotoxicity of natural killer (NK) cells and NK like T cells, which might play a key role in the pathogenesis of endometriosis. The level of MHC-I antigen could be regulated by culture or some biologic factors such as gamma-IFN. PMID- 11775943 TI - [Expression of bcl-2 protein in adenomyosis]. AB - OBJECTIVE: To investigate the expression of B cell lymphoma/leukemia-2 (Bcl-2) protein in adenomyosis and its clinical implication. METHODS: Endometrium specimens were obtained from 16 normal uterus and 32 with adenomyosis. bcl-2 expression in these paraffin embraced specimens was examined by immunohistochemical technique with specific monoclonal antibodies. RESULTS: bcl-2 expression in normal endometrium showed a significant cyclic variation. bcl-2 expression of glandular cells in both eutopic and ectopic endometrium of adenomyosis also showed a significant cyclic variation. bcl-2 expression in endometrium of adenomyosis was stronger than that in normal endometrium, and bcl 2 expression in ectopic endometrium was stronger than that in eutopic endometrium. CONCLUSION: The decrease of cellular apoptosis resulted from the high bcl-2 expression may play an important role in the pathogenesis of adenomyosis. PMID- 11775944 TI - [Study on the relationship between a polymorphism of tumor necrosis factor-alpha gene and the pathogenesis of polycystic ovary syndrome]. AB - OBJECTIVE: To investigate the relationship between -308 bp polymorphism in tumor necrosis factor-alpha (TNF-alpha) gene promoter region and the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: One hundred eighteen Chinese women with PCOS (44 were obese, and 74 nonobese) and 54 controls were genotyped according to the fragment length [87 bp and(or) 107 bp] of TNF-alpha gene promoter by the technique of polymerase chain reaction-restriction fragment length polymorphism. The distribution of TNF1 genotype (87/87) and TNF2 genotype (87/107 + 107/107) in the two groups and their relations to parameters of glucose metabolism associated with PCOS were compared. RESULTS: There was no significant difference in the distribution of TNF1 and TNF2 genotypes between PCOS group and the controls (P > 0.05). In obese PCOS group, only significant lower insulin sensitivity index was found in TNF-1 genotype as compared with TNF2 genotype (P < 0.05). In nonobese PCOS group, there was no significant difference in all parameters of glucose metabolism between TNF1 and TNF2 genotype. All parameters of glucose metabolism in obese patients with TNF1 genotype were significantly different from those in nonobese with TNF1 genotype. However, significant differences were found only in some parameters when comparison was made between obese and nonobese within the TNF2 genotype group. CONCLUSION: There is no association between TNF-alpha gene -308 bp polymorphism and the pathogenesis of polycystic ovary syndrome, but PCOS patients with TNF2 genotype may associate with improvement to certain degree on abnormal glucose tolerance usually existed in obese PCOS women. PMID- 11775945 TI - [Analysis of the relevant morphological characteristics observed in intracytoplasmic sperm injection]. AB - OBJECTIVE: To analyze the morphological characteristics of oocyte, sperm and blastomere-stage embryo and correlate with intracytoplasmic sperm injection (ICSI) embryo score. METHODS: ICSIs were done in M II oocytes harvested after superovulation with long-protocol gonadotropin releasing homone agonist. Various morphological characteristics of oocyte, sperm and blastomere-stage embryo were identified and correlated with the embryo score. RESULTS: Forty-three ICSI cycles were completed. Twelve out of 31 male factor infertile couples and 2 out of 12 with fertilization failure during previous standard in vitro fertilization-embryo transfer cycles achieved clinical pregnancy, resulting in a pregnancy rate of 38.7% and 16.7% per transfer respectively. Severe teratospermia and abnormal cytoplasm of the oocytes, such as cytoplasmic central dark granulas, inclusions, had significantly low embryo score (P < 0.01). The size of perivitelline space had no influence on the result. The oocytes without oolemma elasticity during ICSI process had a lower oocyte survival rate compared with those with oolemma elasticity (P < 0.01). The clinical pregnancy rate per transfer between transferred embryo with average score higher and lower than 3 was significantly different (52% vs 10%, P < 0.001). CONCLUSION: Some morphological characteristics of gamates correlate with the embryo quality and clinical pregnancy rate. They can be used to assess and improve the clinical management during ICSI. PMID- 11775946 TI - [Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 protein in the implantation window phase of endometrium]. AB - OBJECTIVE: To study the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-3 (TIMP-3) protein in the implantation window phase of endometrium and the role of MMP-9 and TIMP-3 on embryo implantation. METHOD: Immunohistochemical analysis was employed to demonstrate the population of the MMP-9 and TIMP-3 positive cell in endometrium of different phases of menstrual cycle. RESULTS: The positive cells of these soluble proteinases were found to be located in the endometrial epithelial cells and stromal cells. The quantitative analysis of MMP-9 and TIMP-3 proteins demonstrated an increase in staining exent from proliferative endometrium to the endometrium of implatation window phase, and an decrease to late-secretory endometrium in comparison with the implantation window phase. CONCLUSION: Expression of MMP-9 and TIMP-3 in the implantation window phases of endometrium is specific and may play an important role in regulating the depth of trophoblast invasion during embryo implantation and may be involved in endometrial stromal breakdown during menstruation. PMID- 11775947 TI - [Prediction of malignant transformation of hydatidiform mole by mRNA determination of matrix metalloproteinases and tissue inhibitor of metalloproteinases]. AB - OBJECTIVE: To investigate the relationship between the messenger RNA(mRNA) levels of matrix metalloproteinases(MMP-9, MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) and malignant transformation of hydatidiform mole. METHODS: Total RNA were isolated from tissues of 22 normal chorionic villi samples and 37 cases of hydatidiform mole. The mRNA expression of MMP-9, MMP-2, TIMP-1, TIMP-2 genes were determined by RT-PCR. RESULTS: The differences of the mRNA expression of MMP-9, MMP-2, TIMP-1, TIMP-2 genes in the tissues of hydatidiform mole and normal preganacy villus were not significant (P > 0.05). The ratio of MMP-9/TIMP-1 in molar tissues with malignant transformation was higher than those in molar tissues without malignant transformation and in normal villus. CONCLUSION: It is a correlative relation beween MMP-9/TIMP-1 and malignancy of hydatidiform mole. The ratio of MMP-9/TIMP-1 might be used as an index for prediction of malignant transformation of hydatidiform mole. PMID- 11775948 TI - [Study on ascite of ovarian cancer]. AB - OBJECTIVE: Analysis of correlative factors in ascite of ovarian cancer. METHODS: The clinical data of 72 patients with ovarian cancer admitted to our hospital from 1993 to 1998 were analyzed retrospectively. RESULTS: 73.5% of patients with ovarian cancer had cancer cells in ascite, the incidence of ascite was 81.9%, III and IV stage ovarian cancer with cancer cells in ascite were 91.2%, positive rate of tumor cells obviously increased in cases whose ascite were more than 1,000 ml, in cases with tumor surface infiltration as well as with metastasis to omentum, intestine and diaphragm. CA125 value in ascite without cancer cells was (324.94 +/- 527.64) kU/L, whereas in ascite with cancer cells it was (5,172.64 +/- 1,432.61) kU/L. Whether cancer cells were positive or negative. Chromosomal aneuploidy was detected in two third of the cases. CONCLUSION: Routine examination of cancer cells, chromosome and CA125 in ascite with ovarian cancer may improve the diagnostic accuracy. PMID- 11775949 TI - [Prevent from bleeding after medical abortion through prolonged application of mifepristone with misoprostol for terminating early pregnancy]. AB - OBJECTIVE: To find out the optimal doses regimen of mifepristone with misoprostol for termination early pregnancy. METHODS: A randomized comparative study in 1,621 women requesting medical abortion at < or = 49 days from 9 hospitals was conducted in Hebei, women were randomly divided into 2 groups by 2:1 ratio. Study group (n = 1,118) women took mifepristone 50 mg immediately, then 25 mg b. i. d(total amount of 300 mg), plus misoprostol 600 micrograms at 8:00 in the morning on 3th day, and plus misoprostol 200 micrograms respectively at 8:00 in the morning on 4th, 5th, 6th day. In control group (n = 494), mifepristone 50 mg immediately, then, 25 mg b. i. d (total amount of 150 mg), plus misoprostol 600 micrograms at 8:00 in the morning on 3th day. RESULTS: In study group and control group, the complete abortion rate was 98.39% and 88.06% respectively, bleeding duration was (8.2 +/- 2.8) days and (12.3 +/- 3.9) days. There was no difference of side effects between the two groups. CONCLUSION: Mifepristone taken 300 mg plus misoprostol 1,200 micrograms orally for 6 days is an optimal dose regimen for termination of early pregnancy. PMID- 11775950 TI - The preparation of rapidly disintegrating tablets in the mouth. AB - Elderly people, children and patients sometimes have difficulties swallowing tablets. To solve this problem, a novel method of preparing tablets that disintegrate rapidly in the mouth was developed. A tablet with high porosity is required for rapid disintegration, but such a tablet is generally fragile. To make a tablet having both high porosity and practical strength, amorphous sucrose, which has good compactability, was used. Mannitol powder with freeze dried amorphous sucrose was tableted at low compression and stored under certain conditions. The tablet disintegrated rapidly in the mouth, because of its high porosity. The tensile strength of the tablet increased remarkably during storage, while the porosity of the tablet seemed almost unchanged. The results of thermal analysis and powder x-ray diffraction measurement showed that the amorphous sucrose in tablet crystallized during storage. The increase in the tensile strength of the tablet was due to crystallization of the amorphous sucrose and formation of new internal contact points in the tablet. It was concluded that this crystalline transition method is a very useful method to prepare a rapidly disintegrating tablet. PMID- 11775951 TI - Preparation of pellets of different shape and their characterization. AB - Pellets of different shapes were produced by modifying the processing parameters of a standardized pellet formulation. The target size of these pellets was 1-1.4 mm. Initially the shape of the pellets was assessed by visual observation. In total, eight batches of pellets were produced of which four were considered to be round, whereas the other four deviated from the spherical shape by various degrees. The different pellet fractions were then characterized for their size, shape, surface, and density properties employing a series of established techniques in order to identify the most appropriate method of characterization and the interrelationships between these properties. The results showed that attempting a task of preparing pellets of graded differences in shape from the same powder blend can result in changes of other important pellet properties such as surface roughness, surface area, and pellet dimensions. Some of these changes could be anticipated by considering the process variables involved, whereas others changed in a manner for which there is no immediate explanation. PMID- 11775952 TI - Practical limitations of tableting indices. AB - The purpose of this study was to utilize tableting indices to distinguish between materials with varying degrees of compactibility by establishing a quantitative relationship between indices and compactibility. Compactibility in this study is restricted to tablet strength and friability alone. Nine mixtures with varying degrees of compactibility were tableted and the tensile strength and friability of the tablets were determined. The tableting indices of these mixtures were determined using an Instron Universal testing machine. An artificial neural network program was used to establish a quantitative relationship between indices and tablet strength and friability. Six new powders were used to validate the models describing the relationship between indices and tablet strength and friability. These powders were compressed into tablets and their strength and friability were determined. Their indices were also determined. The established models were used to predict tablet strength and friability from index values. The predicted values were compared with the experimentally determined values. There was little correlation between the predicted and experimentally determined values for tablet strength and friability. It was also found that materials or mixtures having almost similar indices had remarkably different compactibilities. It was concluded that models created to predict compactibility using one set of materials may not be able to successfully predict the compactibility of a new material. This calls into question the practicality of indices. PMID- 11775953 TI - Pulmonary peptide delivery: effect of taste-masking excipients on leuprolide suspension metered-dose inhalers. AB - The purpose of this study was to evaluate the effect of taste-masking excipients on in vitro and in vivo performance of a leuprolide metered-dose inhaler (MDI) suspension formulation. Taste-masking excipients (aspartame and menthol) were added to a leuprolide suspension MDI formulation. The leuprolide MDI formulation with the taste-masking excipients was characterized in terms of milling time, particle size distribution, dose delivery and uniformity, and drug absorption in dogs. The data were compared with a formula that did not contain taste-masking excipients. It was found that the longer milling time for the leuprolide suspension with the taste-masking excipients was required to obtain a similar particle size distribution compared with the formula without taste-masking excipients using a fluid energy mill. Although measurable differences in mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were not observed between the two formulations, the percent of particles < or = 5 microns and the actuator retention for the formula with the taste-masking excipients were significantly different from the formula without taste-masking excipients using the Marple-Miller cascade impactor. Taste-masking excipients did not show a significant effect on valve delivery and through-can dose uniformity. However, the mean ex-actuator dose was 150.4 mg for the formula with the taste masking excipients and 162.2 mg for the reference formula, respectively, indicating a significant difference. In tracheostomized dogs, both formulations showed comparable pharmacokinetic parameters including Cmax, Tmax, AUC0-12 and bioavailability (F%), indicating that the taste-masking excipients do not have an effect on lung absorption of leuprolide acetate. Therefore, inclusion of taste masking excipients in the leuprolide MDI suspension formulation showed a significant impact on drug micronization, exactuator dose, and particle deposition pattern. Mechanistically, the unfavorable performance of leuprolide MDI in the presence of taste-masking excipients could be due to modification of the properties of the suspension itself and alteration of propellant evaporation following actuation. PMID- 11775954 TI - Evaluation and selection of bio-relevant dissolution media for a poorly water soluble new chemical entity. AB - The purpose of this work is to develop a bio-relevant dissolution method for formulation screening in order to select an enhanced bioavailable formulation for a poorly water-soluble drug. The methods used included a modified rotating disk apparatus for measuring intrinsic dissolution rate of the new chemical entity (NCE) and the USP dissolution method II for evaluating dissolution profiles of the drug in three different dosage forms. The in vitro dissolution results were compared with the in vivo bioavailability for selecting a bio-relevant medium. The results showed that the solubility of the NCE was proportional to the concentration of sodium lauryl sulfate (SLS) in the media. The apparent intrinsic dissolution rate of the NCE was linear to the rotational speed of the disk, which indicated that the dissolution of the drug is a diffusion-controlled mechanism. The apparent intrinsic dissolution rate was also linear to the surfactant concentration in the media, which was interpreted using the Noyes and Whitney Empirical Theory. Three formulations were studied in three different SLS media using the bulk drug as a reference. The dissolution results were compared with the corresponding bioavailability results in dogs. In the 1% SLS--sink conditions -the drug release from all the formulations was complete and the dissolution results were discriminative for the difference in particle size of the drug in the formulations. However, the data showed poor IVIV correlation. In the 0.5% SLS medium--non-sink conditions--the dissolution results showed the same rank order among the tested formulations as the bioavailability. The best IVIV correlation was obtained from the dissolution in 0.25% SLS medium, an over-saturated condition. The conclusions are: a surfactant medium increases the apparent intrinsic dissolution rate of the NCE linearly due to an increase in solubility. A low concentration of surfactant in the medium (0.25%) is more bio-relevant than higher concentrations of surfactant in the media for the poorly water-soluble drug. Creating sink conditions (based on bulk drug solubilities) by using a high concentration of a surfactant in the dissolution medium may not be a proper approach in developing a bio-relevant dissolution method for a poorly water soluble drug. PMID- 11775955 TI - The relationship between structures and in vitro properties of a polyanhydride implant containing gentamicin sulfate. AB - Laboratory scale injection-molding equipment was utilized to fabricate an implant consisting of poly(FAD:SA 1:1) and 20% (w/w) gentamicin sulfate. Characterizations were performed to determine the molecular weight and glass transition temperature of poly(FAD:SA 1:1). A study was carried out to investigate the relationships between the in vitro performance, morphology, and micro-structures of the molded implants. It was found that implants produced with different structures exhibited different physical integrities in water, i.e., cracking or non-cracking. For the non-cracking implants, a skin-core structure formed by an oriented skin layer was observed under a polarized light microscope. The same morphology was not seen in the cracking implants. The crystal orientation in the skin layer of the non-cracking implants was further identified using a wide-angle x-ray diffraction method (WAXD). No crystal orientation could be found in the cracking implants by WAXD. Furthermore, studies were carried out to evaluate the in vitro drug release for implants showing different degrees of integrity in water. The in vitro drug release of the cracking implants was markedly faster than that of the non-cracking implants due to the pronounced initial drug-burst effect as a result of crack formation in the implants. PMID- 11775956 TI - Effect of carrier excipient and processing on stability of indorenate hydrochloride/excipient mixtures. AB - The purpose of this investigation was to determine the solid-state chemical stability of a model drug, indorenate hydrochloride, as a function of carrier excipient and mixing process. Physical mixtures and granules were prepared by tumble mixing and alcoholic granulation with and without binder. Stability of the mixtures was estimated using differential scanning calorimetry and isothermal degradation studies at 40, 50, and 60 degrees C. Average first-order degradation constants at 25 degrees C, extrapolated from isothermal studies, were much lower for indorenate hydrochloride after tumbling mixing with microcrystalline cellulose (3.45 x 10(-5) day-1) than those obtained after tumbling mixing with lactose (112.0 x 10(-5) day-1). Distribution of the drug on the excipient's surface, through granulation with and without Povidone, increased the average drug degradation rates in granules with microcrystalline cellulose (36.2 x 10(-5) day-1) as well as in granules with lactose (326 x 10(-5) day-1). Partially amorphous lactose (spray-dried lactose) showed higher average degradation rates (310.5 x 10(-5) day-1) than crystalline lactose (199.3 x 10(-5) day-1). It appears that the amorphous portion of the drug as well as that of reacting excipients play a major role in affecting the reaction rate. The calorimetric studies showed a strong solid-solid interaction between indorenate hydrochloride and lactose, suggesting chemical incompatibility. This strong solid-solid interaction was characterized by disappearance of typical transition peaks of lactose at temperatures above 200 degrees C and the development of new peaks at about 130-170 degrees C. No major changes in transition peaks were observed in mixtures of microcrystalline cellulose and indorenate hydrochloride, suggesting chemical compatibility. Calorimetric results allow the prediction of the chemical incompatibility between indorenate hydrochloride and lactose observed in isothermal degradation studies. PMID- 11775957 TI - Enhanced drug dissolution and bulk properties of solid dispersions granulated with a surface adsorbent. AB - A combination of solid dispersion and surface adsorption techniques was used to enhance the dissolution of a poorly water-soluble drug, BAY 12-9566. In addition to dissolution enhancement, this method allows compression of the granulated dispersion into tablets. Gelucire 50/13 (polyglycolized glycerides) was used as the solid dispersion carrier. Hot-melt granulation was performed to adsorb the melt of the drug and Gelucire 50/13 onto the surface of Neusilin US2 (magnesium alumino silicate), the surface adsorbent. Dispersion granules using various ratios of drug-Gelucire 50/13-Neusilin US2 were thus prepared. The dissolution profiles of BAY 12-9566 from the dispersion granules and corresponding physical mixtures were evaluated using USP Type II apparatus at 75 rpm. The dissolution medium consisted of 0.1 N hydrochloric acid (HCl) with 1% w/v sodium lauryl sulfate (SLS). Dissolution of BAY 12-9566 from the dispersion granules was enhanced compared to the physical mixture. The dissolution of BAY 12-9566 increased as a function of increased Gelucire 50/13 and Neusilin US2 loading and decreased with increased drug loading. In contrast to the usually observed decrease in dissolution on storage, an enhancement in dissolution was observed for the dispersion granules stored at 40 degrees C/75% relative humidity (RH) for 2 and 4 weeks. Additionally, the flow and compressibility properties of dispersion granules were improved significantly when compared to the drug alone or the corresponding physical mixture. The ternary dispersion granules were compressed easily into tablets with up to 30% w/w drug loading. The extent of dissolution of drug from these tablets was greater than that from the uncompressed dispersion granules. PMID- 11775958 TI - Determination of indomethacin crystallinity in the presence of excipients using diffuse reflectance near-infrared spectroscopy. AB - Studies were conducted to investigate the use of near-infrared spectroscopy for determining the crystallinity of indomethacin in multi-component physical mixtures. Three calibration sets of amorphous/crystalline indomethacin physical mixtures were prepared over the composition range of 0-100% crystallinity. Each of the three calibration sets was diluted step-wise with increasing amounts of a single excipient (Avicel, alpha-lactose monohydrate, or sodium chloride). Near infrared spectra were obtained after each round of dilutions using diffuse reflectance sampling on samples contained in glass vials. After a second derivative transformation, standard curves were constructed by plotting percent indomethacin crystallinity against the ratio of responses at two wavelengths. At dilution levels up to 75% Avicel or lactose, the calibration models demonstrated high coefficients of determination and low standard errors. Dilution with sodium chloride did not produce comparable results and it was necessary to use partial least-squares regression to achieve a similar level of error. These findings were confirmed with separate validation sets. An investigation of instrument error showed that the impact of instrument variability on quantification generally increased as a function of the dilution level. PMID- 11775959 TI - The effect of formulation composition and dissolution parameters on the gel strength of controlled release hydrogel tablets. AB - The impact of hydrogel polymers and dissolution media on tablet gel strength, Gamma, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Gamma was measured using a previously reported method. The drug dissolution profiles were similar, irrespective of polymer type or dissolution media (DI water, 0.1 N HCl, and pH 6.8 phosphate buffer), at the same % w/w level of polymer. Gamma, however, showed large and significant differences (p < or = 0.05) between tablets containing different polymers and between different dissolution media. Gamma values were HPMC KI00MP > HPC HXF > carbomer 971P (same % w/w) with absolute Gamma values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Gamma for HPMC based tablets was independent of changes in dissolution media, while the Gamma values for HPC tablets were 18% lower in acid and buffer than in DI water. Of the polymers tested, carbomer based tablets had the lowest Gamma values in all dissolution media and an unexpected 58% lower Gamma in buffer compared with DI water or acid. Gamma provides a quantitative measure of the effect of formulation and dissolution parameter changes on tablet gel layer strength, under in vitro stress conditions that may parallel in vivo tablet performance, but which cannot be deduced from a comparison of dissolution profiles or polymer viscosity. PMID- 11775960 TI - Interaction of [D-Trp6, Des-Gly10] LHRH ethylamide and hydroxy propyl beta cyclodextrin (HPbetaCD): thermodynamics of interaction and protection from degradation by alpha-chymotrypsin. AB - PURPOSE: The purpose of this study is to investigate the mechanisms and thermodynamics of the interaction between hydroxypropyl beta-cyclodextrin (HPdetaCD) and [D-Trp6, des-Gly10] LHRH ethylamide (deslorelin), a peptide drug. METHODS: We used UV and fluorescence spectroscopy to study the interaction of HPbetaCD and deslorelin. Circular dichroism was used to study the conformational changes induced in deslorelin upon interaction with HP beta CD. The thermodynamics of the interaction of deslorelin and HPbetaCD was studied using isothermal titration calorimetry (ITC). We also determined the effect of HPbetaCD on the degradation of deslorelin by alpha-chymotrypsin. RESULTS: UV and fluorescence spectroscopy indicated that HPbetaD induced a change in polarity of the environment surrounding the chromophores of deslorelin. Wavelength selective fluorescence indicated an increase in the fluorescence polarization of deslorelin with an increase in excitation wavelength in the presence of HPbetaCD suggesting that tryptophan is present in a media of reduced mobility. Circular dichroism studies indicated that HPbetaCD stabilizes the conformation of deslorelin. In addition, ITC indicated an exothermic reaction between deslorelin and HPbetaCD with a low enthalpy of binding of approximately -600 cal/mol and a binding affinity of approximately -1.25 x 10(2) M-1. Finally, the rate of degradation of deslorelin by alpha-chymotrypsin was decreased by 33% in the presence of HPbetaCD. CONCLUSIONS: These results indicate that there is an interaction between HPbetaCD and deslorelin, which involves the inclusion of aromatic amino acids of deslorelin into the hydrophobic cavity of the cyclodextrin. This inclusion, providing steric hindrance, may be one of the mechanisms by which HPbetaCD reduces enzymatic hydrolysis of deslorelin. PMID- 11775961 TI - The influence of plasticizer on heat-humidity curing of cellulose acetate phthalate coated beads. AB - The objectives of the present study are to investigate the effect of plasticizer type and level on the curing of cellulose acetate phthalate (CAP) coated beads with and without the presence of humidity. Theophylline beads were coated in a fluidized-bed with CAP dispersion (Aquacoat CPD) plasticized by a water-insoluble plasticizer, diethyl phthalate (DEP), or a water-soluble plasticizer, triethyl citrate (TEC), at various levels. The coated heads were cured at a heat-only condition (50 degrees C for 24 hr) and a heat-humidity condition (50 degrees C/75% RH for 24 hr). Rapid drug release in the acidic media was found for both heat-only and heat-humidity cured beads when plasticizer was not used in the coating dispersion, indicating that the heat-humidity curing is ineffective without the presence of plasticizers. When plasticizer was incorporated in the coating formulations, heat-humidity curing effectively improved the acid resistance of the coated films at all plasticizer levels investigated. The minimum plasticizer level required to obtain enteric release profiles for heat humidity cured beads coated at an outlet coating temperature of 46 degrees C was 15%. This limit was further decreased when the beads were coated at a lower temperature due to a less plasticizer loss at the lower coating temperature. Between the two plasticizers, less TEC was lost during the coating process, and TEC was more effective compared to DEP with regards to heat-humidity curing at the 10% plasticizer level. The enteric release profiles were reproducible following a 7-day drying period at 40 degrees C for all heat-humidity cured beads that had initially passed the enteric release dissolution test. The rapid leaching of TEC and DEP into the. PMID- 11775963 TI - Recipient of the 2002 Pioneer Award. Robert H. Foote, BS, MS, PhD. PMID- 11775962 TI - Preliminary assessment of the immune response to Olea europaea pollen extracts encapsulated into PLGA microspheres. AB - In this study, poly (D,L-lactide-co-glycolide) (PLGA) microspheres encapsulating Olea europaea pollen extracts were prepared by using the double emulsion (w/o/w) based on a solvent evaporation/extraction method. The resulting microspheres were 1.93 microns in size. The total allergen loading and surface-associated allergen were 8 and 0.64%, respectively. The release of the allergen from the microspheres showed a biphasic profile with an initial burst release followed by a sustained release phase. Finally, the polyacrylamide gel electrophoresis (SDS-PAGE) results showed that the encapsulation process does not affect the stability of the protein. We describe here some preliminary observations concerning the use of these microspheres as parenteral antigen delivery systems for immunization with O. europaea pollen extracts, in a small animal model, the mouse. PMID- 11775964 TI - The transmission of mitochondrial DNA following assisted reproductive techniques. AB - Mitochondria, among other functions, generate energy in the form of ATP. The chondrial genome, located within each mitochondrion, encodes some of the polypeptides associated with the electron transfer chain (ETC) and ATP production. Transcription and replication of mitochondrial DNA (mtDNA) is dependent upon the import of transcription and replication factors encoded by the nucleus. Certain point mutations and large-scale deletions to mtDNA can be either severely debilitating or lethal. The transmission and inheritance of mtDNA [not readable: see to offspring is strictly regulated and specific to each species. In many mammalian systems, paternal mtDNA is eliminated very early during embryonic development. However, it is possible that the paternal molecule could be extruded to those cells destined to become trophoblasts and may act as a regulator of embryonic cell fate. Furthermore, the increasing use of more sophisticated assisted reproductive techniques has led to the incorporation of extraneous mtDNA in both the reconstructed oocyte and embryo with transmission to the offspring at varying degrees. PMID- 11775965 TI - Microfluidic technology for assisted reproduction. AB - The physical tools used in assisted reproduction have changed little over several decades. Microfluidics is an emerging technology that allows a fresh examination of the way assisted reproduction is performed. Here we review our work to develop microfluidic devices to perform the functions required in assisted reproduction. These functions include loading/unloading, culture, chemical manipulation, and mechanical manipulation of embryos and oocytes. Basic microfluidic theory and microfluidic device design and operation are discussed. Results are presented for mechanical removal of cumulus cells and for embryo culture. Results suggest that microfluidic systems will lead to improved efficiencies in assisted reproduction. PMID- 11775966 TI - Application of electronic estrus detection technologies to reproductive management of cattle. AB - Artificial insemination and embryo transfer programs are dependent on efficient and accurate detection of estrus. Visual observation is accurate at detecting animals in estrus, but efficiency ranges from approximately 50 to 70%. Electronic technologies have been developed in attempts to improve estrus detection efficiency. Commercially available electronic devices for estrus detection are based on changes in physical activity (pedometers), changes in electrical resistance of reproductive tract secretions (intravaginal resistance probes) or mounting activity (mount detectors). All of the commercially available electronic estrus detection devices can improve the efficiency of estrus detection in cattle. Pedometers are most applicable to lactating dairy cattle and have greater accuracy and efficiency when combined with visual observation. Intravaginal resistance measurement is perhaps the least practical method of estrus detection because of labor and animal handling requirements. Individual resistance measurement may have practical application for confirming other inconclusive signs of estrus. Mount monitors have the broadest application to beef and dairy cattle. HeatWatch, the only real-time radiotelometric system available, requires the least labor and animal handling and provides data on the time and duration of each mount. The less expensive stand-alone mount monitors also provide the necessary information for optimum timing of insemination and embryo transfer, but are more labor intensive. PMID- 11775967 TI - Computer assisted semen analyzers in andrology research and veterinary practice. AB - The evaluation of sperm cell motility and morphology is an essential parameter in the examination of sperm quality and in the establishment of correlations between sperm quality and fertility. Computer-assisted sperm analysis (CASA) allows an objective assessment of different cell characteristics: motion, velocity, and morphology. The development and problems related to this technology are raised in this review, paying particular attention to the biases and standardization requirements absolutely needed to obtain useful results. Although some interesting results, mainly in humans, have already been obtained, many questions remain, which have to be answered to allow for further development of this technology in veterinary medicine, clinical fertility settings, physiological, and toxicology research activities. The main problem is related to the standardization and optimization of the equipment and procedures. The different CASA instruments have all demonstrated high levels of precision and reliability using different sperm classification methodology. Their availability gives us a great tool to objectively compare sperm motility and morphology and to improve our knowledge and ability to manipulate spermatozoa. PMID- 11775968 TI - The placenta as a contributor to production of large calves. AB - Unusually high birth weights frequently occur in calves born from cultured bovine embryos. The mechanism(s) through which in vitro manipulations during early cleavage are translated to enhanced fetal growth is (are) incompletely understood. Accelerated growth is primarily prenatal, and the placenta of an in vitro-derived conceptus could account for abnormal fetal growth. Results from a systematic comparison of placental morphology and function in bovine concepti produced in vitro versus in vivo are discussed. PMID- 11775969 TI - New gene transfer methods. AB - The intentional introduction of recombinant DNA molecules into a living organism can be achieved in many ways. Viruses have been making a living by practicing gene transfer for millennia. Recently, man has gotten into the act. The paradigm employed is fairly straightforward. First, a way must be found to move genetic information across biological membrane barriers. Then, presumably, DNA repair mechanisms do the rest. The array of methods available to move DNA into the nucleus provides the flexibility necessary to transfer genes into cells as physically diverse as sperm and eggs. Some of the more promising alternative strategies such as sperm-mediated gene transfer, restriction enzyme-mediated integration, metaphase II transgenesis, and a new twist on retrovirus-mediated gene transfer will be discussed, among other methods. PMID- 11775970 TI - Nuclear transfer technologies: between successes and doubts. AB - Cloning of mammals by nuclear transfer can lead to the birth of healthy adult animals but more often compromises the development of the reconstructed embryos. A high incidence of fetal and postnatal losses has been observed in several species, revealing the existence of long-lasting effects induced by the nuclear transfer procedures. Remodeling of donor chromatin by the recipient cytoplasm after nuclear transfer is frequently associated with the deregulation of specific genes, and recent observations point to the potential importance of time dependent DNA methylation events in the occurrence of these alterations. Screening strategies to design nuclear transfer procedures that would mimic the epigenetic remodeling occurring in normal embryos are being designed, and improvement in the efficiency of procedures could imply a pre-conditioning of donor cells. Early mammalian development appears to be rather tolerant to epigenetic abnormalities, raising the possibility that even a fully functional reprogrammed genome may have been subjected to some epigenetic alterations. Bringing nuclear transfer to routine practice requires greater knowledge and understanding of the basic biological processes underlying epigenetic controls of nuclear activities. An important issue at present is to limit the production of those aberrant phenotypes that may result in significant insult to the nature and welfare of animals. PMID- 11775971 TI - Physiological classification of anovulatory conditions in cattle. AB - Evaluation of follicular growth patterns by ultrasound combined with measurement of circulating reproductive hormones has allowed designation of three functionally critical follicular sizes during the final stages of follicular growth: emergence (-4 mm), deviation (-9 mm), and ovulation (variable from 10 to 20 mm). Classification of anovulatory conditions on the basis of these three critical points is logical and provides for rational diagnosis and treatment of the underlying physiological condition. In extreme undernutrition, there is growth of follicles to emergence but not to deviation; however, the underlying pathophysiology is not defined because of relatively few scientific investigations of this condition. Anovulatory conditions with growth of follicles to deviation but not to ovulatory size have been extensively studied. Undernutrition and/or suckling can cause this anovulatory condition. It is characterized by a greater negative feedback effect of estradiol on GnRH/LH pulses than found in normally cycling cows. Another anovulatory condition that is common in high producing lactaing dairy cows is characterized by growth of follicles to larger than ovulatory size, such as is observed in cows with follicular cysts. This condition is characterized by an insensitivity of the hypothalamus to the positive feedback effects of estradiol. Thus, these last two common anovulatory conditions appear to be primarily due to changes in the responsiveness of the hypothalamus to estradiol. Treatments that increase circulating progesterone concentrations can help in the treatment of these two conditions by potentially altering GnRH/LH pulses and allowing the final stages of follicular growth or resetting the hypothalamic responsiveness to the positive feedback effects of estradiol. PMID- 11775972 TI - Animal genetic resources in Brazil: result of five centuries of natural selection. AB - Brazil has various species of domestic animals, which developed from breeds brought by the Portuguese settlers soon after their discovery. For five centuries, these breeds have been subjected to natural selection in specific environments. Today, they present characteristics adapted to the specific Brazilian environmental conditions. These breeds developed in Brazil are known as "Crioulo," "local," or naturalized. From the beginning of the 20th century, some exotic breeds, selected in temperate regions, have begun to be imported. Although more productive, these breeds do not have adaptive traits, such as resistance to disease and parasites found in breeds considered to be "native." Even so, little by little, they replaced the native breeds, to such an extent that the latter are in danger of extinction. In 1983, to avoid the loss of this important genetic material, the National Research Center for Genetic Resources and Biotechnology (Cenargen) of the Brazilian Agricultural Research Corporation (Embrapa) decided to include conservation of animal genetic resources in its research program Conservation and Utilization of Genetic Resources. Until this time, they were only concerned with conservation of native plants. Conservation has been carried out by various research centers of Embrapa, universities, state research corporations, and private farmers, with a single coordinator at the national level, Cenargen. Specifically, conservation is being carried out by conservation nuclei, which are specific herds in which the animals are being conserved, situated in the habitats where the animals have been subjected to natural selection. This involves storage of semen and embryos from cattle, horses, buffaloes, donkeys, goats, sheep, and pigs. The Brazilian Animal Germplasm Bank is kept at Cenargen, which is responsible for the storage of semen and embryos of various breeds of domestic animals threatened with extinction, where almost 45,000 doses of semen and more than 200 embryos exist presently. An important challenge for this program is to make the different segments of society realize the importance of the conservation of animal genetic resources. PMID- 11775973 TI - In vitro embryo production in buffalo species: state of the art. AB - In the last several years, there has been an increasing interest in in vitro embryo production (IVEP) technologies for faster propagation of superior germplasm in buffalo because of the low efficiency of superovulation (SO) and embryo transfer (ET) programs in this species. Although the IVEP efficiency has improved, embryo yield and development to term are still very low. This paper reviews the progress made in optimizing the IVM, IVF, and IVC systems. It also highlights the importance of embryo cryopreservation, which might critically contribute to the diffusion of ET procedures in the field. The acquisition of more information on embryo physiology, metabolism, and culture requirements in this species is critical to optimize the efficiency of advanced reproductive strategies. Further studies are also needed to improve the cryopreservation of IVEP embryos. The second part of the work underlines the potential impact of ovum pick-up (OPU) technique combined with IVEP on genetic improvement of buffalos. The OPU technique is a non-invasive and repeatable procedure for recovering large numbers of meiotically competent oocytes from antral follicles of live animals. Our experience, in buffalo, has demonstrated that OPU is superior to SO because it can yield more transferable embryos (TE) per donor on a monthly basis (2 TE vs 0.6, respectively). Therefore this technology has great potential to improve the genetic progress of buffalo through the maternal lineage. PMID- 11775974 TI - In vitro production of embryos in swine. AB - In recent years, progress has been achieved in the production of pig embryos through IVM and IVF techniques. Cytoplasmic maturation of oocytes has been improved by modifications to IVM procedures. However, the historical problem of polyspermic penetration still remains a major issue to be solved. Recent studies indicate that the type of IVF medium and certain modifications to that medium can reduce polyspermy. Efforts should be directed to increase the developmental competence and quality of embryos. At present, many embryo culture (EC) media are available that can overcome the historical 4-cell block and support development of early in vivo derived embryos to the blastocyst stage. In contrast, blastocyst development of in vitro produced embryos in these culture media varies significantly. Furthermore, morphology and cell numbers in in vitro produced blastocysts are inferior to their in vivo counterparts. However, several modifications to EC techniques have improved embryo quality and developmental competence. Testing embryo viability through surgical transfer to recipient animals has resulted in acceptable pregnancy rates with moderate litter sizes. Although reliable in vitro systems are available for the generation of pig embryos, the problem of polyspermy and poor embryo development hamper their large scale implementation. Further research efforts should be directed to improve oocyte/embryo quality and the methods to minimize polyspermy through development of novel IVM, IVF, and EC techniques. PMID- 11775976 TI - Advancements in cryopreservation of domestic animal embryos. AB - The development of embryo freezing technologies revolutionized cattle breeding. Since then, advancements in cryobiology, cell biology, and domestic animal embryology have enabled the development of embryo preservation methodologies for our other domestic animal species, including sheep and goats. Recently, technologies have been developed to cryopreserve pig embryos, notorious for their extreme sensitivity to cooling; horse embryo cryopreservation is in its infancy. While cryopreservation can enhance the utilization of in vitro embryo production technologies, cryosurvival of in vitro-produced (IVP) or micromanipulated embryos is less than that of in vivo-derived embryos. This review outlines recent efforts in livestock embryo cryopreservation. In the near future, use of preserved embryos could be a routine breeding alternative for all livestock producers providing 1) preservation methods for maternal germplasm, 2) global genetic transport, 3) increased selection pressure within herds, 4) breeding line regeneration or proliferation, and 5) methodology for genetic rescue. PMID- 11775975 TI - Advances in the production and propagation of transgenic goats using laparoscopic ovum pick-up and in vitro embryo production technologies. AB - Laparoscopic ovum pick-up (LOPU) is a convenient methodology by which oocytes can be recovered and used either for in vitro production of zygotes or as a source of cytoplasts in nuclear transfer (NT) procedures. The pregnancy and transgenesis rates achieved with IVM/IVF of LOPU-sourced oocytes followed by subsequent DNA microinjection of zygotes are similar to the rates obtained when using in vivo produced oocytes or zygotes. Similarly, pregnancy rates and kids born by using LOPU-sourced and in vitro matured oocytes as recipient cytoplasts in NT programs are comparable with those reported by others using in vivo matured oocytes collected by oviduct flushing. The use of LOPU allows for improved control over the stage of maturation/development of the oocytes and produced zygotes, a less invasive means of recovery, thereby allowing for repeated usage of the oocyte donor animals and the ability to source the oocytes from live animals of known health status. In addition, because of large follicular responses that can be obtained from prepubertal animals, LOPU followed by IVM/IVF has demonstrated great potential for the early propagation of valuable animals, in particular, transgenic animals. PMID- 11775977 TI - Cryopreservation of gametes and embryos of non-domestic species. AB - Many species of mammals are threatened or endangered. Methods of assisted reproduction that are being used with increasing frequency to produce offspring of domestic animals and humans are often viewed as offering innovative ways to reproduce non-domestic species as well. Uncounted millions of live young of domestic or laboratory species have been produced from gametes and embryos stored at -70 degrees C or below, sometimes for as long as 25 to 35 yrs. Such methods of cryopreservation are now being applied with increasing frequency and urgency to preserve gametes and embryos of non-domestic and threatened species to establish "genome resource banks" or "frozen zoos." But levels of success to produce live young from such cryopreserved gametes or embryos vary considerably from species to species, as well as from individual to individual. It is sometimes thought that differences among species in fundamental characteristics of their gametes may determine the efficacy of cryopreservation and the production of live young. However, it may not be that ineffective cryopreservation is responsible for low success rates. Rather, the limiting factor may be insufficient information and knowledge of the most basic reproductive biology of such non-domestic species. Even standard methods of cryopreservation may be completely adequate to act as a "temporary" expedient to preserve germplasm of non-domestic species to permit time to acquire a fuller understanding of the biology and behavior of non domestic species. PMID- 11775978 TI - Current status of sperm cryopreservation: why isn't it better? AB - Cryopreservation extends the availability of sperm for fertilization; however, the fertilizing potential of the frozen-thawed sperm is compromised because of alterations in the structure and physiology of the sperm cell. These alterations, characteristics of sperm capacitation, are present in the motile population and decrease sperm life-span, ability to interact with female tract, and fertilizing ability. The etiology of such alterations may represent a combination of factors, such as inherited fragility of the sperm cell to withstand the cryopreservation process and the semen dilution. Although the former is difficult to address, approaches that make-up for the dilution of seminal fluid may be sought. The aim of this work is to review aspects of sperm cryopreservation paralleled by events of capacitation and evaluate the possible roles of sperm membrane cholesterol, reactive oxygen species, and seminal plasma as mediators of cryopreservation effects on sperm function. PMID- 11775979 TI - Cryopreservation of Bos taurus vs Bos indicus embryos: are they really different? AB - Cryopreservation with storage at very low temperatures is essential to make full use of this technology for both biological and commercial reasons. However, most mammalian cells will die if exposed to these temperatures unless they are exposed to cryoprotectant solutions and cooled and warmed at specific rates. Lowering temperature below 0 degree C introduces the risk of intracellular ice formation, which likely increases rapidly as the temperature falls. Evidence indicates that ice formation during cooling can cause significantly more damage than ice formation during warming. Comparisons of the toxicity of various cryoprotectants indicated that ethylene glycol (EG) is a nontoxic compound for murine and bovine embryos. The 3.6 M EG solution resulted in similar high survival rates when compared with nonfrozen embryos; deleterious effects of high concentrations of EG became apparent at 7.2 M. The use of EG provides a nontoxic method for the rapid and simplified controlled freezing of in vivo bovine compact morulae-early blastocyst, avoiding the risk of injury caused by high concentrations of cryoprotectants usually required for vitrification. However, in vivo embryos used for freezing and thawing require further studies to understand the ultrastructural changes during the freezing procedure with EG as the single cryoprotectant, especially between Holstein and Nelore cows. This paper describes the ultrastructure of bovine compact morulae-early blastocysts derived by in vivo methods from Holstein and Nelore cows to investigate the fresh morphology as well as that after exposure to cryoprotectant and cryopreservation by conventional slow freezing, quick freezing (nitrogen vapor), and vitrification. PMID- 11775980 TI - Effects of in vivo prematuration and in vivo final maturation on developmental capacity and quality of pre-implantation embryos. AB - In current in vitro production (IVP) systems, oocytes lack in vivo dominant and preovulatory follicular development, which may compromise pregnancy and viability of calves born. When an oocyte sets off in vivo on the road toward fertilization, it contains numerous transcripts and proteins necessary to survive the first few cell cycles of embryonic development. It is not yet known during which period of development the oocyte builds up the store, possibly primarily during the major growth phase of the oocyte, which is completed at the time a follicle reaches the size of 3 mm. Here, we investigated to what extent the later phases of follicular development, such as prematuration in the dominant follicle before the LH surge and ensuing final maturation in the preovulatory follicle, contribute to oocyte competence and development into viable biastocysts. Recent studies on in vivo vs in vitro oocyte maturation employed oocytes from an identical preovulatory development by applying ovum pick-up (OPU) twice (before and 24 h after the LH surge) in each cow treated for superovulation with a controlled LH surge. The embryo recovery rates at Day 7 of IVC after IVF were similar: 44% (97/219) for in vivo- vs 41% (87/213) for in vitro-matured oocytes, which shows that the natural environment during final maturation is not essential for the mere in vitro development of the prematured oocyte beyond the 8- to 16-cell stage. However, in vivo maturation appeared to contribute to the oocyte's quality in a more subtle way, as indicated by a significant increase in the proportion of expanded blastocysts and a more physiological degree of chromosome aberrations of the embryos. In blastocysts derived from in vivo-matured oocytes, 21% of the embryos were mixoploid vs 50% from in vitro-matured oocytes, concomitant with a higher number of cells (96 vs 54 per normal blastocyst). The expression pattern of a set of six developmentally important genes was, however, not significantly altered in blastocysts derived from in vivo-matured oocytes. Certain deviations were observed compared with the levels of entirely in vivo-developed control blastocysts, which suggests that the beneficial effects of in vivo maturation are possibly exerted at initial stages of embryonic development. Prematuration in vivo, occurring in a dominant follicle developing from about 8 mm into the preovulatory follicle, is accompanied by changes in protein synthesis of the cumulus oocyte complex (COC). Presumably, the differentially expressed proteins are involved in equipping the oocyte with further developmental competence. Although we have unraveled some important biochemical and cellular biological features of the oocyte, further research on in vivo processes is essential to improve in vitro embryo production in practice. PMID- 11775981 TI - The control of follicular wave development for self-appointed embryo transfer programs in cattle. AB - Our expanding knowledge of the control of follicular wave dynamics during the bovine estrous cycle has resulted in renewed enthusiasm for the prospects of precisely controlling the follicular and luteal dynamics and finely controlling the time of ovulation. Follicular wave development can be controlled mechanically by ultrasound-guided follicle ablation or hormonally by treatments with GnRH or estradiol and progestogen/progesterone in combination. Treatment of cattle with GnRH in combination with prostaglandin F2 alpha (PGF) 7 d later and a second GnRH 48 h after PGF (known as Ovsynch) has resulted in acceptable pregnancy rates after fixed-time AI in lactating dairy cows and in recipients in which embryos were transferred without estrus detection. Alternatively, treatments with estradiol and progestogen/progesterone-releasing devices resulted in synchronous emergence of a new follicular wave and, when a second estradiol treatment was given 24 h after device removal, synchronous ovulation and high pregnancy rates to fixed-time AI. Self-appointed embryo transfer (without estrus detection) using estradiol and progesterone treatments have resulted in pregnancy rates comparable with those obtained with recipients transferred 7 d after estrus. Furthermore, estradiol and progesterone treatments combined with PGF and eCG (given 1 d after the expected time of wave emergence) have resulted in high rates of recipients selected for transfer (84.6%) and an overall pregnancy rate of 48.7% (recipients pregnant/recipients treated). Estradiol and progestogen/progesterone treatments have also been widely used for self-appointed superstimulation protocols with equivalent embryo production to that of donor cows superstimulated using the traditional approach beginning 8 to 12 d after estrus. In summary, exogenous control of luteal and follicular development facilitates the application of assisted reproductive technologies in cattle by offering the possibility of planning the superstimulation of donors and synchronization of recipients at a self-appointed time, without the necessity of estrus detection and without sacrificing results. PMID- 11775982 TI - Leptin regulation of reproductive function and fertility. AB - Leptin, a 16-KD protein secreted primarily by adipose tissue, was first discovered in the search for a satiety signal. When administered into the brain, leptin depresses appetite. Interestingly, hyperphagic, obese, transgenic mice with leptin deficiency were noted to be reproductively incompetent, and administration of leptin restored their fertility. These pivotal observations led to numerous studies on the site of action of leptin within the hypothalamo hypophyseal-gonadal axis, and a variety of models have been used ranging from the prepubertal condition to fasting suppression of reproductive hormones. The preponderance of studies thus far has focused on how leptin serves as a metabolic signal of energy balance within the neuroendocrine system, particularly as a regulator of GnRH/LH secretion. Less research has been conducted with other components of the reproductive system, but local effects of leptin have been demonstrated in the gonads where hyperleptinemia suppresses steroidogenesis and potentially affects gamete maturation. This presentation will review the major concepts for the role of leptin in the modulation of fertility and will consider the potential use of leptin in assisted reproductive technology and embryo transfer. PMID- 11775983 TI - High rates of embryonic loss, yet high incidence of multiple births in human ART: is this paradoxical? AB - Humans have low natural fecundity, as the probability of establishing a viable conception in any one menstrual cycle is 20-25% for a healthy, fertile couple. There are numerous underlying causes for this low rate of human fertility, not the least of which are intrinsic abnormalities within the oocyte and/or embryo, which likely account for greater than 50% of failed conceptions. During assisted reproduction technology (ART) interventions, controlled ovarian stimulation is used to obtain several oocytes in attempts to increase the likelihood of having at least one developmentally competent embryo available for transfer. However, current techniques for identifying the competent embryo(s) are by no means perfect. These limitations, coupled with pressures to maximize the chance of pregnancy, typically result in the transfer of multiple embryos. Not surprisingly, this practice has resulted in an unacceptably high rate of multiple pregnancies arising from ART. During the last few years, concerted efforts have focused on reducing these rates. Programs for ART are developing patient-specific policies, restricting the number of embryos to transfer. In addition, strategies are being adopted to improve the accuracy for selecting viable embryos for transfer. One such strategy involves further refinement of morphological criteria associated with improved viability by considering, for example, pronuclei disposition, nucleolar organization, and identification of the fast-cleaving embryos with only mononucleate blastomeres. Another strategy employs pre implantation genetic diagnosis (PGD) whereby a biopsied blastomere is tested for ploidy using fluorescence in situ hybridization (FISH). A final strategy involves extending the duration of culture to the blastocyst stage, thereby allowing self selection of those embryos capable of proceeding to blastulation and exclusion of those less viable embryos that succumb to developmental arrest. Together, these strategies are enabling fewer embryos of higher quality to be transferred. Accordingly, the overall pregnancy rate from ART continues to increase, while the rate of triplet and higher order multiple births continues to decline. Nevertheless, the high incidence of intrinsic developmental anomalies in human oocytes inevitably will continue to result in a high degree of embryonic loss in ART. PMID- 11775985 TI - Magic in nursing: some ideas about unexplainable situations. PMID- 11775984 TI - Blastocyst culture in human IVF: the final destination or a stop along the way? AB - In the field of human IVF, culturing embryos to the blastocyst stage has gained popularity within the past few years. The impetus to transfer blastocysts has been spurred by several factors: 1) the desire to improve implantation rates in infertility patients, 2) a desire to reduce the multiple pregnancy rate by transferring fewer embryos, 3) the desire to perform pre-implantation genetic diagnosis, and 4) the advent of sequential media. Although culturing human embryos to the Hastocyst stage has improved implantation rates and reduced the incidence of multiple pregnancies in some patient populations, it has not worked for all populations of infertility patients. Factors that may affect the ability of a human embryo to reach the blastocyst stage include the patient's age, cohort of ova retrieved, the use of intracytoplasmic sperm injection of blastomere biopsy, culture conditions, or intrinsic factors within the embryo itself. Culture of human embryos to the blastocyst stage can be an effective method for improving implantation rates and reducing the high order multiple pregnancy rates seen in human IVF clinics when more than three embryos are transferred. PMID- 11775986 TI - One veteran's view of nursing. PMID- 11775987 TI - "Life, Loss and Living" program. PMID- 11775988 TI - Looking through the years: 1947. A national student nurse recruitment program. PMID- 11775989 TI - The breadth and depth of nursing. PMID- 11775991 TI - A new career after retirement. PMID- 11775990 TI - A long, evolving nursing career. Interview by Marie Manthey. PMID- 11775992 TI - Want a change? Try nursing. PMID- 11775993 TI - Thinking globally at the "Global Strategies" conference, and acting locally at the "Focus on Women" conference--a report from Uganda. PMID- 11775994 TI - HIV & breastfeeding: what's a mother to do? PMID- 11775995 TI - House, senate still await conference committees' reports on AIDS funding. PMID- 11775996 TI - Domestic terrorism in 2001 diverts attention from 20 years of AIDS. PMID- 11775997 TI - AIDS confidentiality doesn't stop subponea of medical records. PMID- 11775998 TI - WTO nations agree to more flexibility for AIDS-drug access. PMID- 11775999 TI - Report: HIV infections rise most rapidly in Eastern Europe. PMID- 11776000 TI - Foundations join effort to reduce mother-to-child infection. PMID- 11776001 TI - Contributions to global AIDS fund diminish after Sept. 11. PMID- 11776003 TI - Housing. Challenges to New York City's policies to proceed in court. PMID- 11776002 TI - Senate hearings on AIDS pandemic may come next spring. PMID- 11776004 TI - AIDS as grounds for appeals fails in California, N.C. cases. PMID- 11776005 TI - Florida privacy laws prevent release of AIDS patients' data. PMID- 11776006 TI - Southwestern Bell employee to continue AIDS bias claims. PMID- 11776007 TI - HIV status helps to reduce prison time for drug conviction. PMID- 11776009 TI - Court: state law specifies crimes for mandatory procedure. PMID- 11776008 TI - Revised CDC guidelines include referral for legal services. PMID- 11776010 TI - Cultural validation of pediatric pain assessment tools: Jordanian perspective. AB - The purpose of this study was to examine the cultural validity, reliability, and preference of three pain assessment tools among 95 Jordanian children. Pain intensity was assessed using the Poker Chip, the Faces, and the Word Description Scales. The test-retest reliability and the convergent validity were supported for the three scales. Jordanian children preferred the Poker Chip Tool to the Faces Scale and the Word Descriptive Scale. Gender differences in relation to scale preference were evident: female children preferred the Poker Chip Tool and male children preferred the Faces Scale; such differences were contributes of the socialization process within the Arab culture. The three scales are valid, reliable, and can be used with confidence to assess pain among Jordanian children. Findings also showed that children have a subculture of their own regardless of their cultural orientation. Findings have implication to nurses in Jordan as well as to transcultural nursing. PMID- 11776011 TI - Vaginal microbicides for HIV/STI prevention in Zimbabwe: what key informants say. AB - The purpose of this study was to assess the acceptability of vaginal microbicides as prevention methods for heterosexually transmitted HIV. Interviews were conducted with key informants in and around Harare using a semistructured questionnaire with probes. Twenty-seven interviews were conducted with a total of 48 informants. Most women were enthusiastic about the products but had concerns about safety and how the use of these products might affect their relationships with their husbands. Many men were concerned that women would be able to use the products without their consent or knowledge. Several products may be acceptable in this culture but must be introduced within the existing gender power structure. This study provides a model for involving community leaders in the design of culturally appropriate clinical trials. PMID- 11776012 TI - Daily living practice of the life-satisfied Thai elderly. AB - The purpose of this study was to determine whether the life satisfaction of Thai elderly depends on their daily living practice. A comparative design was used to study 73 matched pairs of elderly people who perceive themselves as life satisfied or life dissatisfied. Scores of 85% and above on the life satisfaction instrument were used as a criteria to identify the elderly with life satisfaction. The sample was drawn from elderly clubs in four provinces of the eastern border of Thailand. Data were collected using structured interviews regarding the elderly's daily living practices on physical, mental, social, and economic domains. A two-tailed dependent t test was used to reveal mean scores both overall and for each domain of the daily living practices of the elderly participants. It was found that the life satisfaction group of elderly had significantly higher scores than their dissatisfied counterparts. The findings suggest the importance of Thai elderly's good practice on food habits, regular exercise, seeking knowledge toward health, religious activity involvement, good relationships with others, and well-planned income and expenses resulting in life satisfaction. Thus, nurses can promote life satisfaction of Thai elderly by motivating these factors that are generally uncommon practices in the Thai elderly culture. Future studies using a longitudinal quasi-experimental design to employ these positive daily living practice to promote life satisfaction of the life dissatisfied elderly is recommended. PMID- 11776013 TI - Outcomes of a transcultural nursing immersion experience: confirmation of a dimensional matrix. AB - Schools of nursing are positioned to increase cultural awareness for students and potentially change practice. Dimensions of culturally focused field experiences were investigated to determine the relevancy of the dimensions of the Matrix for Personal and Professional Growth Through a Transcultural Immersion Experience. A questionnaire was developed and administered to two samples of nursing students following participation in an immersion experience. Results provided evidence of validation for major dimensions of the matrix, including situational predetermining factors, modifying factors, transitional factors, and outcomes of the matrix. The model for transcultural nursing immersion experiences was conceptualized, and propositions were generated. PMID- 11776014 TI - Proposed standards for transcultural nursing. Transcultural Nursing Society. AB - For the past 3 years, the Minnesota Chapter of the Transcultural Nursing Society has focused efforts on the development of standards for transcultural nursing practice. The standards, based on Leininger's culture care theory and Campinha Bacote's model of cultural competence, are intended to foster excellence in transcultural nursing practice, to provide criteria for the evaluation of nursing care, to be a tool for teaching and learning, to increase the public's confidence in the nursing profession, and overall to advance the field of transcultural nursing. The standards are presented as an invitation for individual and collective reflection and commentary. PMID- 11776015 TI - Big changes in the Indian Health Service: are nurses aware? AB - Unparalleled challenges currently face the Native American health care system. These challenges are a result of several factors, including (a) external pressures to reduce the overall cost of health care in the United States, (b) increased assumption of responsibility for delivery of health care by tribal governments, (c) decreased direct supervision by the Indian Health Service (IHS), (d) insufficient funding for Indian health care, and (e) increased interest of managed care to contract with tribal service units for health care. This article explores the opportunities and challenges facing Native American health care delivery and examines nursing policy issues pertinent to the current state of the IHS. PMID- 11776016 TI - On the drafting of standards for transcultural nursing practice. PMID- 11776017 TI - Cross-cultural health education: materials on the World Wide Web. AB - Language differences between health providers and consumers create a central barrier to the delivery of health education. This article presents the results of an analysis of more than 75 bi/multilingual health sites available on the Internet. The review criteria and a summary of the key features of the best sites are presented. Limitations common to most sites are identified. Recommendations and caveats in the use of bilingual health information sites are introduced. PMID- 11776018 TI - Utilizing traditional storytelling to promote wellness in American Indian communities. AB - Utilizing storytelling to transmit educational messages is a traditional pedagogical method practiced by many American Indian tribes. American Indian stories are effective because they present essential ideas and values in a simple, entertaining form. Different story characters show positive and negative behaviors. The stories illustrate consequences of behaviors and invite listeners to come to their own conclusions after personal reflection. Because stories have been passed down through tribal communities for generations, listeners also have the opportunity to reconnect and identify with past tribal realities. This article reports on a research intervention that is unique in promoting health and wellness through the use of storytelling. The project utilized stories to help motivate tribal members to once more adopt healthy, traditional life-styles and practices. The authors present and discuss the stories selected, techniques used in their telling, the preparation and setting for the storytelling, and the involvement and interaction of the group. PMID- 11776019 TI - Developing a transcultural patient care Web site. AB - The development of a transcultural Web site created by a multidisciplinary committee in a large medical center is described. The purpose of this Web site is to give direct patient caregivers immediate, around-the-clock access to various types of transcultural information that can serve as an aid in the provision of culturally competent care. This article outlines the steps to developing the Web site and provides a description of the types of informational resources available on it. PMID- 11776020 TI - Founder's focus: cultural diffusion trends, uses, and abuses in transcultural nursing. PMID- 11776021 TI - Detecting residual ischemia and identifying coronary artery disease after myocardial infarction using dobutamine technetium-99m-MIBI SPECT. AB - OBJECTIVE: To evaluate dobutamine technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography (Dobu-ECT) in detecting residual ischemia and identifying coronary vessel disease after myocardial infarction. METHODS: Sixty-two patients with confirmed myocardial infarction were studied with Dobu-ECT at the time of coronary artery angiography. Dobutamine was administered intravenously in incremental rates from 5 to 40 micrograms.kg-1.min 1 at 3-minute intervals. At the highest infusion rate, 7.4 x 10(8) Bq 99mTc-MIBI was injected intravenously, and tomographic imaging was performed after one hour. Resting images were taken after 24 hours, with a second dose of 99mTc-MIBI. RESULTS: The sensitivity of Dobu-ECT in detecting residual ischemia of myocardial infarction was 76%, which was higher than dobutamine electrocardiography (Dobu ECG). Regardless of the single-, double- or triple-vessel diseases, Dobu-ECT was superior to Dobu-ECG in identifying residual ischemia (56% vs 4%, 86% vs 27%, 100% vs 47%, P < 0.01, respectively). The incidence of residual ischemia in patients receiving thrombolytic therapy was 67%, lower than patients without thrombolysis (72%) or those with an old myocardial infarction (94%). But the differences were not statistically significant. Dobu-ECT detected only 56% of ischemias in non-infarct related myocardium. Eighty-two percent of all significantly stenosed vessels were detected with Dobu-ECT, and 84% of patients with multivessel disease could be accurately identified. The sensitivity of Dobu ECT was significantly greater for detecting severe stenosis over moderate stenosis. The sensitivity for detecting stenosis in the right coronary artery was greater than left anterior descending or left circumflex, but its specificity was lower. CONCLUSION: Dobu-ECT can identify residual ischemia, as well as its location and extent after myocardial infarction. Dobu-ECT can also accurately detect significantly stenosed vessels. PMID- 11776022 TI - Electrical remodeling of membrane ionic channels of hypertrophied ventricular myocytes from spontaneously hypertensive rats. AB - OBJECTIVE: To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes. METHODS: Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole-cell configuration of patch-clamp technique, with normal Wistar rats ventricular myocytes as controls. We observed depolarizing currents (sodium current, INa; L-type calcium current, L-ICa) and repolarizing currents (inward rectifier potassium current, IK1; delayed rectifier potassium current, IK; transient outward potassium current, Ito) and compared the differences between normal and hypertrophied myocytes. RESULTS: The heart to body weight ratio of Wistar rats and SHRs was 3.70 +/- 0.29 mg/g and 5.66 +/- 0.46 mg/g, respectively (P < 0.001), and the mean cell membrane capacitances were 189.94 +/- 56.59 pF and 280.68 +/- 67.98 pF, respectively (P < 0.05). These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes. The amplitude of L-Ica of SHRs (1944 +/- 466.8 pA) was significantly greater than that of Wistar rats (1136 +/- 383.3 pA) (P < 0.001), and the current density was 6.93 +/- 1.71 pA/pF and 6.19 +/- 2.85 pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56.01 +/- 13.36 ms vs 43.63 +/- 17.89 ms, P < 0.001). The amplitude of INa of SHRs (6132.5 +/- 1162.9 pA) was significantly greater than that of Wistar rats (3613.9 +/- 794.44 pA) (P < 0.001), but there was no difference when normalized to cell capacitance (24.61 +/- 6.72 pA/pF vs 24.95 +/- 6.99 pA/pF). Channel activation and inactivation time constants were also the same. The amplitude of IK of SHRs (3461.5 +/- 1967.10 pA) was greater than that of Wistar rats (2302.4 +/- 893.72 pA) (P < 0.05), but there was no difference when normalized to cell capacitance (12.38 +/- 5.46 pA/pF vs 11.86 +/- 3.59 pA/pF). The inward portion of IK1 of SHRs was significantly lower than that of Wistar rats (11.3 +/- 2.26 pA/pF vs 14.3 +/- 3.00 pA/pF, P < 0.05), but there was no difference in the outward portion (2.360 +/- 0.86 pA/pF vs 2.957 +/- 1.27 pA/pF). The current density of Ito of SHRs (8.21 +/- 6.64 pA/pF) was significantly lower than that of Wistar rats (19.16 +/- 6.17 pA/pF) (P < 0.001), but channel kinetics were similar, suggesting that the reduction of Ito may result from the decrease in channel number. CONCLUSIONS: Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1. there was an increase of L-Ica, INa and Ik, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2. Ito was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge. The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of Ito may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity. Therefore, the reduction of Ito in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling. PMID- 11776023 TI - Advanced glycosylation end products increase diacylglycerol levels in cultured human umbilical vein endothelial cells. AB - OBJECTIVE: To study whether the diacylglycerol (Dia) signaling pathway is stimulated by advanced glycosylation end products (AGEP) and to test the effect of vitamin E and aminoguanidine (AG) on the elevation of Dia induced by AGEP in cultured human umbilical vein endothelial cells (HUVECs). METHODS: The effects of AGEP on Dia levels in cultured HUVEC were studied with radio-enzymatic assay. Quantitative measurements of 32P phosphatidic acid were achieved by thin-layer chromatography and autoradiography. RESULTS: The Dia levels in HUVECs were increased by AGEP modified bovine serum albumin (AGEP-BSA) in a dose-dependent, biphasic manner. The early phase was rapid and transient, peaking at 15 s; the late phase reached the maximal level at 10 min and then decayed slowly. Dia levels in HUVEC exposed to different concentrations (50, 100 and 200 mg/L) of AGEP-BSA (341 +/- 14, 678 +/- 16, and 873 +/- 18 pmol/L, respectively vs control 225 +/- 10 pmol/L) and AGEP-BSA samples with various glycosylation times (4, 8 and 12 weeks) were significantly increased (270 +/- 12, 394 +/- 16, and 556 +/- 19 pmol/L) as compared with the controls. 50 and 100 mmol/L of vitamin E can reduce AGEP-BSA-induced Dia levels from 873 +/- 18 pmol/L to 764 +/- 29 and 441 +/- 21 pmol/L in HUVEC, respectively. In AG-treated (100 mmol/L) groups, the same concentration (100 and 200 mg/L) of AGEP-BSA-induced elevation of Dia was decreased to 312 +/- 8 and 351 +/- 13 pmol/L, respectively. Glycosylated low density lipoprotein (LDL) did not affect Dia levels. CONCLUSION: AGEP causes a robust stimulation of the Dia/protein kinase C pathway in HUVEC. Vitamin E can attenuate the AGEP-BSA-induced elevation of Dia levels. AG can suppress the ability of AGEP-BSA to increase Dia levels in HUVEC. PMID- 11776024 TI - Effect of hormone replacement therapy on heart rate variability in postmenopausal women. AB - OBJECTIVE: To assess the characteristics of autonomic control of heart rate in postmenopausal women before and after hormone replacement therapy (HRT). METHODS: Time domain and spectral domain heart rate variability (HRV) were performed in 58 postmenopausal women before and after HRT. RESULTS: Compared with examinations at baseline, values of all HRV measurements in subjects given HRT were increased at the fourth month (P < 0.05), while they remained unchanged in the control group (P > 0.05). Results showed an inverse correlation between all measures of HRV and mean R-R interval in the treatment group. CONCLUSION: HRT reduces sympathetic drive in postmenopausal symptomatic women. HRV may be an index of imbalance of autonomic control in perimenopausal women. PMID- 11776025 TI - Relationship between serum or tissue ouabain and blood pressure in 1k1c hypertensive rats. AB - OBJECTIVE: To evaluate the role of endogenous ouabain (EO) in the development of hypertension and the characteristics of EO secretion in 1k1c (one kidney, one clipped) hypertensive rats. METHODS: EO content of serum and tissues in 1k1c hypertensive rats and normal control Sprague-Dawley (SD) rats was detected by the method of enzyme linked immunosorbent assay (ELISA). The relationship between serum or tissue ouabain and blood pressure was analyzed in 1k1c hypertensive rats. RESULTS: The ouabain content of serum, heart, kidney, adrenal gland, pituitary and hypothalamus was significantly higher in 1k1c hypertensive rats than that in normal control SD rats (2.25, 2.63, 3.35, 40.37, 3.34, 15.7 micrograms/kg tissue in 1k1c hypertensive rats vs 1.12, 1.79, 1.73, 27.54, 1.83, 10.10 micrograms/kg tissue in control SD rats, respectively. P < 0.05 for all of these comparisons). The ouabain content of the adrenal gland and the hypothalamus was higher than that of other tissues or serum, both in 1k1c rats and in control SD rats. The EO content of serum, kidney and hypothalamus was significantly correlated with blood pressure in 1k1c hypertensive rats (r = 0.59, 0.63, 0.52, respectively. P < 0.05). The ouabain content of heart, liver, adrenal gland and pituitary was not correlated with blood pressure. CONCLUSIONS: EO might play an important role in the development of hypertension in 1k1c hypertensive rats. The adrenal gland may be a major source of EO and the hypothalamus-pituitary-adrenal axis may be involved in the regulation of EO secretion. PMID- 11776026 TI - Emodin on hepatic fibrosis in rats. AB - OBJECTIVE: To investigate effect of emodin on hepatic fibrosis in rats. METHODS: The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCl4 (twice a week for 6 weeks) dissolved in olive oil. The emodin-treated rats were treated with low-dose, mediate-dose and high-dose emodin (20, 40 and 80 mg/kg body weight, once a day for 42 days) dissolved in 0.5% sodium carboxymethylcellulose (CMC), except receiving CCl4. Control group received only olive oil and 0.5% CMC. Liver functions were determined by standard procedure. Serum hyaluronic acid and laminin were determined by radioimmunoassay. Liver hydroxyprolines were determined. Histopathological changes were examined by optical microscopy. RESULTS: Compared with model group, the emodin-treated rats showed (1) liver functions were improved, alanine transaminase (ALT) and alkaline phosphatase (AKP) were obviously reduced, and total protein (TP) and albumin (ALB) were significantly increased; (2) serum hyaluronic acid and laminin were markedly reduced; (3) liver hydroxyproline was significantly decreased; (4) the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant (P < 0.05 or P < 0.01). CONCLUSION: Emodin has effect on hepatic fibrosis in rats. The hepatoprotective of emodin may be one of mechanisms for liver fibrosis. PMID- 11776027 TI - Transfection and expression of HCV-NS5B gene in Huh-7 cells. AB - OBJECTIVE: To study the mechanism of hepatitis C virus (HCV) replication and to test gene therapy for hepatitis C, a human liver cell line expressed HCV RNA polymerase has been established. METHODS: NS5B gene has been transfected into Huh 7 cells by lipofectamine. The results of transfection were confirmed by PCR and Southern blot analysis, and the level of the non-structural protein 5B (NS5B) in Huh-7 cells was detected by Western blot analysis. RESULTS: There were NS5B gene fragments and the expression of NS5B protein in Huh-7c cells transfected with pTeT-NS5B or pcDNA-NS5B plasmid. CONCLUSIONS: We have established a HCV RNA polymerase expression system in Huh-7 cells which can be further used to analyze the mechanism of HCV replication and provide a cell model for gene therapy in vitro. PMID- 11776028 TI - Reactive oxygen species contribute to the induction of superoxide dismutase during heat shock in cultured rat neonatal cardiomyocytes. AB - OBJECTIVE: To explore the influence of reactive oxygen species (ROS) during heat shock on the activity of superoxide dismutase (SOD) and the endurance of cardiomyocytes against hypoxia-reoxygenation damage. METHODS: Cultured rat neonatal cardiomyocytes were divided into 5 groups (n = 6/group): normal control, anoxic control, heat shock, heat shock + SOD (150 U/ml) and exogenous ROS pretreated. Myocytes were first incubated in a CO2 incubator (37 degrees C) with Hank's solution for 30 min, followed by specific pretreatment. Heat shock was performed by incubating the cells in a 43 degrees C incubator for 30 min; exogenous ROS were generated by the reaction of xanthine oxidase with xanthine. After the dishes were returned to normal incubation conditions for 24 h, myocytes underwent hypoxia (3 h) and reoxygenation (1 h). RESULTS: Compared with control groups, ROS production increased after the cells experienced heat shock (1.28 +/- 0.34 nmol/mg.1 protein vs 0.80 +/- 0.23 nmol/mg.protein and 0.74 +/- 0.20 nmol/mg.protein, P < 0.05) or ROS pretreatment (3.30 +/- 0.58 nmol/mg.protein, P < 0.05). 24 hours later, accompanied by attenuated cellular injury, significantly increased SOD activity was found in heat shock (2.55 +/- 0.43 U/mg.protein vs 0.77 +/- 0.12 U/mg.protein and 0.63 +/- 0.09 U/mg.protein, P < 0.05) and exogenous ROS pretreated (2.34 +/- 0.31 U/mg.protein, P < 0.05) groups following reoxygenation. Moreover, opposite results were found when myocytes were treated with SOD during heat shock. CONCLUSIONS: The release of ROS during heat shock triggers delayed myocardial protection by altering the activity of SOD. ROS may play an important pathophysiological role in heat shock induced myocardial protection. PMID- 11776029 TI - Non-X-ray comprehensive measurement for accurate localization of sublabio-septo sphenoidal approach. AB - OBJECTIVE: To use non-X-ray comprehensive measurement for accurate localization of sublabio-septo-sphenoidal approach for shortening operating duration, decreasing hemorrhage, and increasing the success rate of operation. METHODS: Operations in 122 patients suffering from tumors in the sella turcica region used non-X-ray localizations including localization by the angle formed by the glalella, anterior nasal spina and anterior nasal spina-sella turcica; localization by the angle formed by the upper incisors, anterior nasal spina and anterior nasal spina-sella turcica; and localization by anatomical markers (determination of the midline by the nasoseptum and vomer; determination of the anterior wall of the sphenoidal sinus by the foramen of the sphenoidal sinus and vomer body; correction of the site by septum of the sphenoidal sinus; location of the center of saddle by the shape of the floor of the sella and determination of the approach direction by the damaged area in the sella turcica region) were comprehensively employed. Additionally, X-ray localization was used to correct its accuracy. RESULTS: Non-X-ray comprehensive localization was applied to 40 patients for determining the site and depth of the floor of the sella, and the preciseness of the measurement was confirmed with X-ray. Operating duration averages 2.2 hours. Non-X-ray localization was directly applied to 82 patients for comprehensively measuring the floor of the sella, and operations were successful. Operating duration averages 1.5 hours and blood transfusion averages 200 ml. No deaths and severe complications occurred. CONCLUSION: Non-X-ray comprehensive measurement can be directly applied for precisely localizing the floor of the sella. PMID- 11776030 TI - dl-3-n-butylphthalide reduces brain damage in mice with closed head injury. AB - OBJECTIVE: To investigate the protective effect of dl-3-n-butylphthalide (NBP) as an anti-cerebral ischemic drug on brain damage 24 h after closed head injury in mice. METHODS: Closed head injury was induced by dropping a 50-g weight from a height of 18 cm on a metal impounder resting on the parietal bone in mice. RESULTS: The neurotraumatic model induced impairment of memory function, significant cerebral edema, and disruption of the blood-brain barrier. dl-3-n butylphthalide (50 mg.kg-1) given intraperitoneally 5 minutes and 60 minutes after the onset of closed head injury was found to attenuate the impairment of memory function (P < 0.05), alleviate brain edema in the injured cerebral cortex (P < 0.05), and reduce extravasation of plasma protein bound to Evans blue dye by 63.5% (P < 0.01). NBP was also shown to increase the activity of choline acetyltransferase in the injured cortex to 0.83 +/- 0.21 ng.min-1.mg-1 (P < 0.01, compared with 0.48 +/- 0.14 ng.min-1.mg-1 of vehicle group). CONCLUSION: NBP provides therapeutic response in experimental closed head injury. PMID- 11776031 TI - Adjuvant chemotherapy following radical surgery for non-small-cell lung cancer: a randomized study on 70 patients. AB - OBJECTIVE: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small-cell lung cancer (NSCLC). METHODS: Seventy patients with NSCLC (stages I-III) undergoing radical surgery were randomized into two groups. Group 1 (n = 35): combination group, which received adjuvant chemotherapy with cyclophosphamide 300 mg/m2, vincristine 1.4 mg/m2, adriamycin 50 mg/m2, and lomustine 50 mg/m2 on day 1, and cisplatin 20 mg/m2 on days 1-5. The treatment was repeated every 4-6 weeks for 4 cycles, followed by oral administration of ftorafur (FT-207) 600-900 mg/d for 1 year. Group 2 (n = 35): surgery group, which received surgical treatment only. RESULTS: The overall 5-year survival rate was 48.6% in the combination group versus 31.4% in the surgery group, and difference between the two groups was not statistically significant (chi 2 = 3.09, P > 0.05). The 5-year survival rate for patients with stage III disease was 44% and 20.8% in the combination and surgery groups, respectively, showing a statistically significant difference (chi 2 = 5.28, P < 0.025). The 5-year survival rates of patients in stages I-II in the two groups were 60.0% and 54.5%, respectively, and were not significantly different (chi 2 = 0.03, P > 0.75). CONCLUSION: Postoperative adjuvant chemotherapy provides statistically significant improvement in the 5-year survival rate only in patients with stage III NSCLC. PMID- 11776032 TI - Modulation of transforming growth factor beta to platelet-derived growth factor receptor-alpha of human osteoblasts. AB - OBJECTIVE: To investigate the mechanism and the significance of TGF beta in modulating the expression of Platelet-Derived Growth Factor Receptor-alpha (PDGFR alpha) in human osteoblasts. METHODS: The osteoblasts were isolated from human fetal calvaria. The percentage of cell increase (PCI) in every 4 hours was calculated to demonstrate the proliferation of osteoblasts affected by PDGF-AA and TGF beta. The osteoblasts were cultured with TGF beta for 24 hours and with PDGF-AA for another 24 hours, and the cells proliferation was shown by PCI too. The osteoblasts were cultured with TGF beta for 24 h, and the PDGFR-alpha of the cells were measured by immunofluorescent analysis. RESULTS: PCI was increased by 48.2% and 22.4% after PDGF-AA and TGF beta were added into the medium for 24 hours respectively (P < 0.05), and PCI decreased after the removal of the two cytokines. Preincubated with TGF beta for 24 hours and then stimulated with PDGF AA, PCI grew slowly. TGF beta downregulated the expression of the PDGFR-alpha. CONCLUSION: TGF beta can downregulate the mitogenesis of PDGF-AA by lowering the number of PDGFR-alpha. PMID- 11776033 TI - Therapeutic strategy in the management of stage II-IV epithelial ovarian carcinoma. AB - OBJECTIVE: To investigate the optimal time of debulking in stage/II to stage IV epithelial ovarian carcinoma, considering corresponding advantages of both surgery and chemotherapy. METHODS: From January 1989 to December 1996, ninety five stage II to stage IV ovarian cancer patients were treated under two different regimens. Group A-76 cases (2 cases in IIa stage, 4 cases in IIb stage, 6 cases in IIc stage, 58 cases in IIIc stage and 7 cases in IV stage) was managed according to a traditional surgery-chemotherapy regimen; and group B-19 cases (17 cases in IIIc stage and 2 cases in IV stage) was managed with a chemotherapy surgery-chemotherapy regimen. RESULTS: The optimal debulking rate (no macroscopic residual or residual < 2 cm) in group A was significantly lower than in group B, being 32.9% (25/76) and 68.4% (13/19), respectively (P < 0.001). The average survival time of those with a residual focus > 2 cm was shorter than those with a residual focus < 2 cm, in both groups. Sixteen out of the 51 patients with a residual focus > 2 cm had a second debulking operation, among whom 7 had preoperative chemotherapy. All of these 7 patients had either no residuals or residual < 2 cm. In 9 cases without preoperative chemotherapy, the residuals were all > 2 cm. The average survival time among these two groups were significantly different (P < 0.01). CONCLUSION: (1) For those patients in whom optimal debulking was clinically assessed to be possible, timely operation is mandatory. (2) For those inoperable advanced cases, chemotherapy-surgery-chemotherapy regimen is recommended. (3) For those with residuals > 2 cm and were assessed to be difficult to eradicate during second-look operation, multi-route chemotherapy (intro-arterial, intraperitoneal, and systematic) should be given before going on the second debulking operation. Positive attitude and proper regimen would offer better results. (4) A multicenter prospective study would give more decisive conclusion. PMID- 11776034 TI - E test for studying in vitro activity of seven antimicrobial agents against penicillin-susceptible and penicillin-resistant pneumococci. AB - OBJECTIVE: To evaluate the comparative activity of seven oral antimicrobial agents against 100 strains of Streptococcus pneumoniae (S. pneumoniae). METHODS: Total 100 strains of S. pneumoniae were collected from general hospitals in Beijing from June 1996 to June 1997. E test method was used to detect the minimum inhibitory concentration (MIC) values of the following seven drugs against S. pneumoniae: penicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, ceftriaxone, azithromycin and ofloxacin. The breakpoint of susceptibility categories was defined according to NCCLS. RESULTS: 74% of isolates were susceptible (S, MIC 0.06 mg/L) to penicillin, and 5% were penicillin resistant (R, MIC 2 mg/L). The intermediately resistant (I, MIC 0.1-1 mg/L) rate to penicillin was 21%. The total rates of R or I were 26% for penicillin, 6% for both amoxicillin/clavulanate and ceftriaxone, 9% for cefuroxime, 66% and 68% for azithromycin and ofloxacin respectively. Overall 94%, 94% and 91% of the pneumococcal isolates were susceptible to amoxicillin/clavulanate, ceftriaxone and cefuroxime respectively. S. pneumoniae was highly resistant to azithromycin tested as a representative of macrolides (MIC50 and MIC90 both > 256 mg/L, R rate 66%), and had a highly intermediately resistant rate to ofloxacin (I rate 62%). CONCLUSIONS: Our data suggest that in vitro activity of oral amoxicillin/clavulanate was as good as ceftriaxone and cefuroxime. It can be considered as an alternative compound in the treatment of community acquired pneumoniae and other respiratory tract infections caused by multiresistant S. pneumoniae. PMID- 11776035 TI - Immunolocalization of uterine luminal fluid protein (ULF-250) in rat uterus. AB - OBJECTIVE: To access the production of a novel uterine luminal fluid 250 kD protein (ULF-250) during the various phases of the estrous cycle in relation to estrogen concentration, and to validate that the production and secretion of ULF 250 are regulated by estradiol and progesterone. METHODS: An immunohistochemical method was used to localize ULF-250 in rat uteri during each phase of the estrous cycle, and in uteri of ovariectomized rats treated with estradiol and progesterone. RESULTS: Positive immunostaining of ULF-250 occurred in the epithelial cells of the uterus at all phases of the estrous cycle; whereas the stroma was immunonegative. During the proestrus phase of the cycle, the glandular epithelial cells and glandular luminal content were stained strongly. During the estrus phase of the cycle, intense staining occurred in the glandular and uterine luminal epithelial cells, including the luminal content of the glands. In the metestrus phase of the cycle, only uterine epithelial cells were stained; during the diestrus phase, intense staining of the secreted contents of the uterine cavity and the glandular lumen occurred. The distribution of ULF-250 in the uteri of ovariectomized female rats treated with estradiol alone and estradiol plus progesterone were examined. In both groups, intense staining of the glandular luminal epithelial cells of the uterine endometrium occurred; in the estradiol treated animals, only the luminal contents were stained. The present findings suggest that progesterone inhibits the secretion of ULF-250 that is stimulated by estradiol. CONCLUSIONS: ULF-250 is produced by the glandular and luminal epithelial cells of the uterine endometrium and fluctuates with the phases of the estrous cycle. Its production is stimulated by estradiol and its secretion is regulated by progesterone. PMID- 11776037 TI - Screening for mt-DNA mutations in optic neuritis of unknown cause. AB - OBJECTIVE: To investigate mitochondrial DNA (mt-DNA) mutations in optic neuritis of unknown cause (ONUC) and to assess the practical value of mt-DNA mutation detection in etiologically and differentially diagnosing ONUC. METHODS: Thirty patients with ONUC were screened for mt-DNA mutations of nt11778, nt3460 and nt15257 by using SSCP, mutation-specific primer PCR and sequencing. RESULTS: mt DNA mutations were found in twelve of thirty ONUC patients. All of the mutations were at nt11778 position, but no one at nt3460 and nt15257. CONCLUSIONS: Forty percent (12/30) of ONUC patients were caused by an mt-DNA mutation. Combined with other routine measures, screening for mt-DNA mutations in ONUC patients is of great significance in diagnosing ONUC etiologically and differentially. PMID- 11776036 TI - Anisodamine protects against neuronal death following cerebral ischemia in gerbils. AB - OBJECTIVE: To study the effect of anisodamine on neuronal death and hydroxyl radical (OH.) production during forebrain ischemia-reperfusion in gerbils. METHODS: The tested gerbils were divided into 3 groups, including sham-operated, control and anisodamine groups. In each group, there were 8 animals for biochemical examination and 6 animals for histologic study. Forebrain ischemia was induced by occlusion the bilateral common carotid arteries for 10 min in gerbils. 2, 3- and 2, 5-DHBA outputs were determined by high performance liquid chromatography coupled with electrochemical detection. Behavioral change was tested by open field test and neuronal death was assessed by histological examination. RESULTS: The exploratory activities of gerbils in the control group were significantly higher than those in the anisodamine group on all test days. The amount of viable-looking neurons in the medial, middle and lateral CA1 sectors in anisodamine group were 41% +/- 12%, 50% +/- 21% and 67% +/- 15% of the sham-operated gerbils, respectively, being significantly higher than those in the control group (3% +/- 2%, 4% +/- 3% and 7% +/- 4% of sham, P < 0.01). The 2, 3 DHBA outputs in the control group increased by 5 fold of the sham-operated gerbils after reperfusion for 60 min, but the 2, 3-DHBA outputs in the anisodamine group were only 2.4 fold of sham-operated gerbils, being significantly lower than that in the control group (P < 0.01). The 2, 5-DHBA outputs in the control group were significantly higher than those in the sham operated group (P < 0.05). CONCLUSION: Anisodamine has inhibitory effects on neuronal death and OH.production during cerebral ischemia-reperfusion in gerbils. PMID- 11776038 TI - Apoptosis of infiltrating cells in experimental autoimmune uveoretinitis. AB - OBJECTIVE: To investigate the cellular phenotype and apoptosis of infiltrating cells involved in experimental autoimmune uveoretinitis (EAU). METHODS: Immunohistochemical staining and in situ apoptosis staining were performed using monoclonal antibodies to monocytes and macrophages (ED1), major histocompatibility complex (MHC) class-II antigen (OX6), T lymphocytes (R73) and TACS 1 Klenow kit on both ocular sections and wholemounts from Lewis rats after immunization with interphotoreceptor retinoid-binding protein (IRBP). RESULTS: EAU was induced in 12 of 16 Lewis rats with a mean clinical inflammation score of 1.29 +/- 0.7. Influx of monocytes, lymphocytes and MHC class II-positive cells into the uvea and retina was noted after immunization with IRBP. Apoptosis of infiltrating cells was observed in the uvea and retina, and more apoptotic cells were present in the iris and ciliary body compared with those in the choroid and retina. CONCLUSION: Apoptosis of infiltrating cells occurs at the early stage of EAU, which may greatly contribute to the rapid regression of the inflammation induced by IRBP. PMID- 11776039 TI - Influence of the nasal mucociliary system on intranasal drug administration. AB - OBJECTIVE: To study the influence of the nasal mucociliary system on intranasal drug administration and ways of reducing its influence on nasal absorption. METHODS: Rabbit nasopharynx was closed to stop mucociliary function in one group. In the other group, rabbits maintained their mucociliary function. Both groups were given a nasal drip of gentamycin and the serum levels were measured from 0 to 180 minutes after drug administration. To reduce the undesirable effects of the nasal mucociliary system, acetylcysteine was mixed into the gentamycin drops. In addition, nasal nebulization was evaluated in human volunteers as a means of increasing absorption of the drug in the non-ciliary area of the nasal cavity. RESULTS: Nasal mucociliary function reduced intranasal absorption of drug and made the highest absorbing rate and area under the curve (AUC) decrease by 25.1% and 18.2%, respectively. Both the nasal drip containing acetylcysteine and the nebulizer could promote drug absorption in the nasal mucosa. The former made the highest intranasal absorption and AUC increase by 18.0% and 10.7%, respectively. The latter made the absorption increase 1.5-1.6 times. CONCLUSION: The mucociliary system can decrease intranasal drug absorption. Application of acetylcysteine or the use of nebulizer can increase drug absorption. PMID- 11776040 TI - A cDNA located on chromosome 7q32 shows loss of expression in epithelial cell line of nasopharyngeal carcinoma. AB - OBJECTIVE: To isolate and clone the tumor suppressor gene on chromosomal region 7q32 correlated with the carcinogenesis of human nasopharyngeal carcinoma (NPC). METHODS: The genotypes of polymorphic microsatellite markers on 7q32 in DNA from 24 biopsies of nasopharyngeal carcinoma and matched normal blood cells were identified. The expression levels of 20 expressed sequence tags (ESTs) on 7q32 between human nasopharyngeal carcinoma epithelial 1 (HNE1) and primary cultures of normal nasopharyngeal epithelial (PNNE) cells were compared using differential RT-PCR and Northern hybridization. The quantity of AA070437 DNA and mRNA was detected by differential PCR and differential RT-PCR, respectively. RESULTS: Loss of heterozygosity (LOH) was found in 25%-46% of NPC biopsies. AA070437 EST expression was down-regulated in HNE1 cell compared to PNNE cells. The down regulation of AA070437 was found in 30.7% of NPC biopsies and allelic loss of AA070437 was observed in 29.1% of NPC biopsies. CONCLUSION: Our results show that AA070437 EST is negatively related with the occurrence of human NPC and may represent a candidate tumor suppressor gene of NPC on 7q32. PMID- 11776041 TI - Preclinical trials of human erythrocyte superoxide dismutase injection. AB - OBJECTIVE: To assess the quality of human erythrocyte superoxide dismutase (SOD) injection reaching the official standard for its clinical uses. METHODS: Human erythrocyte SOD injection prepared by McCord-Fridovich's method without column chromatography but with some modifications was used in preclinical trials, to observe the general pharmacology and pharmacodynamics of the product. RESULTS: The quality of human erythrocyte SOD injection conformed to the official standard of a biological product, which was found to be non-toxic and did not have any effects on the central and autonomic nervous systems as well as cardiovascular and respiratory systems. The efficacy of anti-inflammation and promotion of immuno-regulation especially on carrageenan and adjuvant-induced polyarthritis were shown in animals. CONCLUSION: Human erythrocyte SOD injection is appropriate for prophylactic and therapeutic uses in clinical trials. PMID- 11776042 TI - Suppression of induced atherosclerosis in h-apo AI transgenic mice by overexpression of human apo AI in the aortic wall. AB - OBJECTIVES: To investigate the inhibitory effect of expressed human apolipoprotein AI (h-apo AI) and high density lipoprotein (HDL) on atherosclerosis development in transgenic mice, and cultivation of smooth muscle cells isolated from the aortic wall of transgenic mice that are able to produce human apo AI in vitro. METHODS: Both h-apo AI transgenic mice and normal C57 mice were fed with either a regular chow or a high-fat diet containing 5% pork lard, 1.25% cholesterol and 0.25% sodium cholate for 14 or 24 weeks respectively. Human apo AI mRNA were detected by Northern blot. Plasma apo AI levels were measured using a radio-immuno-diffusion assay, and plasma lipid levels were measured using a colorimetric assay. Image analysis was performed in order to quantify the fatty streak areas stained with oil red O. In addition, smooth muscle cells isolated from the media layer of the aortic wall of h-apo AI transgenic mice were cultured for the detection of human apo AI produced. RESULTS: Higher levels of h-apo AI mRNA were found in liver, small intestine, kidneys and aortae in transgenic mice than in the controls all on a high-fat diet. The transgenic mice had an increased level of serum apo AI and HDL-cholesterol and the fatty streak area counted at the aortic sinus was approximately 5-fold less in the transgenic mice after feeding with a high fat ration, particularly after 24 weeks. SMC isolated from the transgenic mice aortae were cultivated and able to express h-apo AI mRNA and its related protein. CONCLUSION: Elevation of h-apo AI and HDL in serum and aortic wall of the transgenic mice has a remarkably inhibitory effect on the development of experimental atherosclerosis. PMID- 11776043 TI - p53 mutation, EGFR gene amplification and loss of heterozygosity on chromosome 10, 17 p in human gliomas. AB - OBJECTIVE: To further illustrate the roles of p53 gene, epidermal growth factor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17 p in human glioma progression. METHODS: p53 mutations were scanned in 50 gliomas with various malignant grades using the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, and were confirmed by direct sequencing. LOH for chromosome 10, 17 p and amplification of the EGFR gene were also assessed using Southern blot analysis. RESULTS: p53 mutations were found in 9 of 17 high-grade astrocytomas (53%), 1 of 15 low-grade astrocytomas (7%), and the only subject of eppendymoblastoma but in none of the 10 medulloblastomas and 7 eppendymomas. The majority of gliomas (38/50) analyzed here retained both 17 p alleles. The frequency of p53 mutations was 13% in this group of tumors and increased to 50% (6/12) in tumors with one 17 p allele (P < 0.025). LOH on chromosome 10 was found in 35% (6/17) of high-grade astrocytomas, in 10% (1/10) of medulloblastomas, but in 0% of low-grade gliomas. EGFR gene amplification was found in 9 high-grade gliomas, 60% (6/9) of which also presented LOH for chromosome 10. CONCLUSIONS: These results indicate that p53 inactivation is a common genetic event in astrocytoma progression that may be more strongly associated with the progression of astrocytomas than with their origin. Absence of p53 mutations in 50% of the tumors with one 17 p allele suggests that a tumor suppressor gene other than p53 may be located on chromosome 17 p and involved in progression to malignancy of some gliomas. The loss of alleles on chromosome 10 and the amplification of the EGFR gene appear to be restricted to high-grade tumors, suggesting that these events may be related to tumor progression rather than initiation. PMID- 11776044 TI - Oxidized low density lipoprotein inhibited tissue factor pathway inhibitor mRNA expression in human endothelial cells. AB - OBJECTIVE: To understand the role of oxidized low density lipoprotein (OX-LDL) in the pathogenesis of thrombotic complications in atherogenesis. METHODS: Low density lipoprotein was isolated from normal heparinized blood by density gradient ultracentrifugation and oxidized by CuCl2. Total RNA was extracted from human umbilical vein endothelial cells (HUVECs) exposed to LDL or OX-LDL, using the guanidinium isothiocyanate method. The quantification of tissue factor pathway inhibitor (TFPI) mRNA in HUVECs was carried out by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: HUVECs were able to express TFPI mRNA constitutively. The expression was not affected by LDL but was effectively inhibited by OX-LDL in a time- and dose-dependent manner. CONCLUSIONS: The results suggest that oxidized LDL may play an important role in inducing coagulation in atherosclerotic lesions by the inhibition of expression of TFPI in vascular endothelial cells. PMID- 11776045 TI - Treating traumatic tattoo by micro-incision. AB - OBJECTIVE: To design a micro-incision operation for treating traumatic tattoo. METHODS: With an 11-gauge blade, a micro-incision was made on each side of the small tattoo spot and the tattoo skin was removed. For a longer tattoo particle, a longer incision was needed. The skin incision was sutured with 6-0 silk. For a complex tattoo, dermabrasion could be used first to remove the superficial one so as to expose the deep one which was removed in the same way as mentioned above. When there was a large number of tattoo particles, many operations were needed. RESULTS: Fourteen patients were treated by this method with good to excellent result. CONCLUSION: Micro-incision for treating traumatic tattoo is an effective method. PMID- 11776046 TI - The present situation and expectation on thrombosis and hemostasis study in China. PMID- 11776047 TI - von Willebrand disease in China. AB - PURPOSE: To review the molecular pathogenesis in Chinese patients with von Willebrand disease (vWD) and polymorphisms of von Willebrand factor (vWF) in Chinese population. DATA SOURCES: Both Chinese and English language literature search using MEDLINE (1985-1998), and original articles published in main Chinese and international journals. STUDY SELECTION AND DATA EXTRACTION: After reviewing of the literature, 19 articles of them were selected that specifically addressed the stated purpose. RESULTS: The molecular pathogenesis of vWD was variant. Six cases of point mutation have been found in Chinese patients with vWD. The system of site-directed mutagenesis and expression of vWF gene was constructed. The polymorphisms of vWF gene are very different between Chinese and Gaucasians. CONCLUSION: Combining to gene mutant in vWD patients, the use of site- directed mutagenesis and expression of vWF will help to understand the vWF function. The polymorphisms of vWF gene are useful marker in Chinese for carrier detection and prenatal diagnosis of vWD. PMID- 11776048 TI - Management of steroid-induced osteoporosis. AB - PURPOSE: To review the pathogenesis, clinical presentation, diagnostic assessment and treatment regimens of steroid-induced bone loss. DATA SOURCES: An English language literature search (MEDLINE 1966-1999) and bibliographic reviews of textbooks and review articles. STUDY SELECTION: Cross-sectional and prospective studies with BMD measurements or fracture rate. RESULTS: The greatest rate of bone loss occur during the first 6 to 12 months of steroid therapy, affecting trabecular more than cortical bone. High steroid dosage for a prolonged period, prevalent fracture, hypogonadism, older age, low calcium intake and family history of osteoporosis are risk factors for steroid-induced bone loss. Based on bone density results, patients with osteoporosis or osteopenia with a T-score below -1.5 should receive antiresorptive treatment during steroid therapy. Among the various antiresorptive agents, bisphosphonates have the strongest evidence of preventing steroid-induced bone loss. CONCLUSION: The most important step in the management of steroid-induced osteoporosis is the proper assessment of the individual patient's risk of bone loss, and the selection of appropriate anti resorptive agent for each patient. PMID- 11776049 TI - Retrospect on the research of the cultivation of Gastrodia elata Bl, a rare traditional Chinese medicine. AB - PURPOSE: To review the research on the cultivation of Gastrodia elata Bl, a rare traditional Chinese medicine. DATA SOURCES: The data come from our previous research and published review articles on G. elata cultivation. STUDY SELECTION: After reviewing the research results on G. elata from 1960 to 1995, we selected the core research on G. elata and a complete cultivation technique of rare traditional Chinese medicine G. elata. DATA EXTRACTION: Some important data were arranged in different tables, and new cultivation methods were reviewed. RESULTS: A. mellea has been found to have inhibiting effects on G. elata seed germination. The seeds are able to sprout only when a nutritional relationship exists between G. elata and a fungus of the same genus as M. osmundicola. The sprouted tubers have to set up a symbiotic relationship with A. mellea during their clone propagation period so as to grow normally. CONCLUSIONS: G. elata has to symbiosize with M. osmundicola and A. mellea so as to complete its life cycle from seed to seed. These findings have revealed the secret of the life cycle of G. elata that has been puzzling biological circles for years. PMID- 11776050 TI - Mutation in the leucine-rich repeat of platelet glycoprotein Ib alpha results in defects in its interaction with immobilized von Willebrand factor under flow. AB - OBJECTIVE: To characterize effects of the GP Ib alpha mutation (A156V) on its interaction with von Willebrand factor (vWf) under high fluid shear stress. METHODS: The residue A156 of GP Ib alpha was converted to a valine and the mutant expressed in CHO cells expressing wild-type GP Ib beta and GPIX. The transfected cells were tested for their interaction with a panel of GP Ib alpha antibodies and for rolling on immobilized vWf under high shear. RESULTS: The mutation led to surface expression of a GP Ib alpha polypeptide that adopted a different conformation at its N-terminus because binding of the GP Ib alpha antibody AN51, which has a binding epitope in the N-terminal 35 residues, was eliminated, whereas binding of the others (AK2, MB45, and SZ2, all of which bind to regions C terminal to the AN51 epitope) was normal. Mutant-expressing cells could adhere and roll on immobilized vWf under high fluid shear stress and rolled significantly faster than wild-type cells. CONCLUSION: These studies demonstrate that the mutation A156V results in a conformation change at the N-terminus of GP Ib alpha, which leads to an increase in the dissociation rate of the bond between the GP Ib alpha mutant and vWf. PMID- 11776051 TI - Activated protein C resistance in antiphospholipid thrombosis syndrome. AB - OBJECTIVE: To explore the correlation between antiphospholipid antibodies (APA), activated protein C resistance (APCR) and antiphospholipid thrombosis (APL-T) syndrome and further investigate the mechanism of thrombosis in APL-T syndrome. METHODS: ELISA, PTT-LA and APTT +/- APC methods were used to detect anticardiolipin antibodies (ACA), lupus anticoagulants (LA) and APC R in 20 APL-T syndrome patients. RESULTS: Twenty patients were diagnosed as APL-T. ACA-IgG, M and LA are strongly associated with APL-T. The incidence of APCR in APL-T (75%) was significantly higher than that of the normal group (5%). CONCLUSION: There was high prevalence of APCR in APL-T, which was strongly associated with LA. It is proposed that acquired APCR induced by APA is a key to understanding thrombosis in Chinese APL-T patients. PMID- 11776052 TI - Polymorphism of human platelet alloantigen in Chinese patients with acute myocardial infarction and acute ischemic stroke. AB - OBJECTIVE: To investigate the gene frequencies of 5 major human platelet alloantiqens (HPA 1-5) in Chinese population and to assess if polymorphism of HPA was associated with Chinese acute myocardial infarction (AMI) and acute ischemic stroke (AIS). METHODS: HPA 1-5 genotyping was performed by PCR using allele specific primers and restriction enzyme digestion based on PCR products in 95 AMI cases, 188 AIS cases and 270 normal controls. Gene frequency distribution was tested by Hardy-Weinberg equilibrium and comparison of HPA gene frequencies between the patient and control groups by chi 2 test. RESULTS: The gene frequencies of HPA 1-5 were the followings: HPA1a: 91%; 1b: 9%; HPA 2a: 94%; 2b: 6%; HPA 3a: 83%; 3b: 17%; HPA 4a: 98%; 4b: 2%; HPA5a: 97%; 5b: 3%. We found there were no significant differences in HPA 1-5 gene frequencies between AMI patients and normal controls. In AIS patients group HPA-2a allele frequency was significant higher than in controls, but this allele gene frequency in two groups (0.94 and 0.99) was very close and too many subjects in these two groups were overlapped. Otherwise no differences was found in other 4 HPA systems between cases and controls. CONCLUSION: Polymorphism of HPA were not inherited risky factors and not associated with chinese arterial thrombotic diseases such as AMI and AIS. PMID- 11776053 TI - Basic and clinical study on the antithrombotic mechanism of glycosaminoglycan extracted from sea cucumber. AB - OBJECTIVE: To investigate the antithrombotic mechanism of glycosaminoglycan (GAG) extracted from sea cucumber. METHODS: We studied the effects of GAG on the coagulant pathway by measuring cloting time. The antithrombin mechanism of GAG was checked by assaying its effects on the thrombin activity in normal human pooled plasma, purified human heparin cofactor II system and antithrombin III system. The effects of GAG on the assembly, dispersion, and structure of fibrin gels as well as on the activity of plasmin were studied by means of turbidimetry, electron microscopy, and chromogenic substrate assay. We studied the effect of GAG on the expression and transcription of tissue factor (TF) and thrombomodulin (TM) in LPS (lipopolysaccharide)-stimulated human umbilical vein endothelial cells (HUVECs), and used heparin as a control. HUVECs were treated with different concentrations of GAG (1 microgram/ml, 5 micrograms/ml, and 10 micrograms/ml respectively) and 5 micrograms/ml heparin as a control together with LPS (1 microgram/ml). After incubation for 6 hours, TF and TM were investigated by ELISA and the mRNA study was carried out by RT-PCR. In a clinical trail, a series of variables were observed before and after treatment with GAG in patients recovering from cerebral ischemic stroke or suffering from ischemic heart disease. RESULTS: The TT and APTT were significantly prolonged by GAG (0.1 microgram/ml). GAG inhibited thrombin activity in the presence of HCII with a second order rate constant of 1.14 x 10(7) m-1.min-1, which was 4.6 times higher than that of ATIII. GAG significantly inhibited the polymerization of fibrin monomer and enhanced the activity of plasmin in a concentration dependent manner. GAG could impair TF mRNA expression and up-regulate TM mRNA expression. The result of clinical trail showed that the fat metabolism was enhanced in addition to the anticoagulant and the blood viscosity reducing effects. No side-effect was found. CONCLUSIONS: GAG mainly affected on the intrinsic pathway of blood coagulation. GAG was similar to dermatan sulfate both in the efficiency and in the mechanism of antithrombin. The acceleration of colt lysis by GAG depended on its ability to increase the activity of plasmin, to inhibit the polymerizing of fibrin monomer, and consequently, to alter the architecture of the fibrin net work. This effect on HUVECs appears to be at a transcriptional level and might be relevant for the antithrombotic action of GAG. GAG possess anticoagulant activity in vivo and it is a promising drug for antithrombotic therapy. PMID- 11776054 TI - Differentiation of human hepatoma Hep G2 cells induced by 10-hydroxycamptothecin. AB - OBJECTIVE: To study the differentiation-inducing effect of hydroxycamptothecin (HCPT) on hepatoma Hep G2 cells. METHODS: 3-[4, 5-dimethylthial-2-yl]-3, 5 diphenyl-tetrazolinium bromide (MTT) colorimetric method was used for determining HepG2 cells viability. Alphafetoprotein (AFP) and albumin (ALB) levels were determined with Elisa Kits. RESULTS: The AFP secretion of HCPT-treated cells was reduced by 44.0%-49.2% while the ALB level was increased markedly. CONCLUSION: Hydroxycamptothecin can induce human hepatoma Hep G2 cells to differentiation. PMID- 11776055 TI - Bacterially produced human B7-1 protein encompassing its complete extracellular domain maintains its costimulatory activity in vitro. AB - OBJECTIVE: To investigate which of the two immunoglobulin (Ig)-like domains, immunoglobulin variable region homologous domain IgV (hB7-1 IgV), or immunoglobulin constant region homologous domain IgC (hB7-1 IgC) on human B7-1 molecule contain the receptor binding sites, and to evaluate if the B7-1 molecule expressed in bacteria has biological activity. METHODS: PCR was used to amplify three fragments of hB7-1 IgV, hB7-1 IgC and complete extracellular region of human B7-1 containing both the IgV and IgC domains (hB7-1 IgV + IgC). Three recombinants, pQE9-hB7-1 IgV, pQE9-hB7-1 IgC and pQE9-Hb7-1 (IgV + IgC) were generated by cloning the PCR products into a prokaryote expression plasmid (pQE 9) and were introduced into the host stain M15. The relevant target hexahistidine tagged proteins were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7-1 proteins and [3H]-TdR incorporation. RESULTS: Three recombinant proteins of human B7-1, hB7-1 IgV, hB7-1 IgC and hB7-1 (IgV + IgC) were produced and detected in both soluble and inclusive body forms from engineered bacterial cells. With the presence of anti-CD3 antibody, T lymphocytes proliferated when co-stimulated by bacterially produced hB7-1 (IgV + IgC), but not by either hB7-1 IgV or hB7-1 IgC. CONCLUSIONS: Functional glycoprotein human B7-1 could be produced in bacterial cells. Both extracellular immunoglobulin-like domains are necessary for B7-1 to react with its counter receptors. PMID- 11776056 TI - Azathioprine and methylprednisolone: prevention of chronic cerebral vasospasm in dogs. AB - OBJECTIVE: To study the preventive effects of single use of azathioprine and its combination with methylprednisolone on chronic cerebral vasospasm (CVS). METHODS: A canine model of the "double subarachnoid hemorrhage (SAH)" was established to study the angiogram characteristics of chronic CVS. The effects of azathioprine and its combination with methylprednisolone on the prevention of chronic CVS were observed in a randomized study. The content of malondialdehyde (MDA) and pathological changes in the basilar artery (BA) wall were also analyzed. RESULTS: The results were obtained on the 7th day after subcarachnoid hemorrhage. In the azathioprine group, the BA diameter was 87% +/- 26% of the original BA diameter, and the MDA content of BA wall was 0.03 +/- 0.01 nmol/mg tissue. In the azathioprine plus methylprednisolone group, it was 93% +/- 20% (BA diameter) and 0.02 +/- 0.01 nmol/mg tissue (MDA content). In the control group, the BA diameter was 53% +/- 19% and MDA content was 0.11 +/- 0.05 nmol/mg tissue. Pathological examination confirmed the reduction in BA wall damage in the experimental groups. CONCLUSION: Azathioprine has a preventive effect on chronic CVS following SAH. It may suppress the production of free radicals and reduce damage to the BA wall. Combined use of azathioprine with methylprednisolone allows lower dosage and less complication compared with a single agent, and results in a better outcome. PMID- 11776057 TI - Adenovirus-mediated transfer of beta-galactosidase and prourokinase genes into vein grafts. AB - OBJECTIVE: To study the feasibility of adenovirus mediated gene transfer into vein grafts and the role of the prourokinase gene in protecting vein grafts from thrombosis. METHODS: Fifty-two Wistar rats underwent implantation of reversed autologous jugular vein interposition grafts in the common carotid arteries. Jugular veins were excised and distended with solution containing three different adenovirus vectors (Adv5-CMV, group I; Adv5-CMV/LacZ, group II; Adv5-CMV/Pro-UK, group III) for 30 min, then the jugular veins were reversed and interposed into the divided carotid arteries, and end-to-end anastomoses were performed. The amount of 51Cr-labeled platelets in vein grafts of group I and group III was counted 24 hours postoperatively. On the 14th day, the vein grafts were harvested to examine beta-galactosidase activity and prourokinase (Pro-UK) activity and observe thrombosis in vein grafts. RESULTS: Extensive blue coloration in the area of intima and media of each vein graft in group II was observed. No blue coloration was seen in group I. Pro-UK activity was not detected in the vein grafts of group I. In group III, the amount of Pro-UK gene expression was 308 IU/g tissue. The amount of 51 Cr labeled platelets in group I and group II was (123.7 +/- 19.4) x 10(6)/g dry wt, (34.4 +/- 5.3) x 10(6)/g dry wt, respectively. The thrombosis rate and occlusion rate of the vein grafts in group I were 30% and 10%, respectively. In group III, all vein grafts were patent and free of thrombosis. CONCLUSIONS: Ex vivo gene transfer before vein grafting is feasible using replication deficient recombinant adenovirus and results in a high level of gene expression in vivo. Direct transfer of the Pro-UK gene into vein grafts may prevent thrombosis. PMID- 11776058 TI - Development of cytotoxic cerebral edema in rats following intracaudatum injection of tACPD, an agonist of metabotropic glutamate receptors. AB - OBJECTIVE: To explore the involvement of metabotropic glutamate receptors (mGluRs) in the formation of cerebral edema. METHODS: Male Wistar rats weighing from 250 g to 300 g were used. Trans-1-aminocyclopentane-1, 3-diacarboxylic acid (tACPD), an agonist of mGluRs, was microinjected into the right caudatum. Brain water content was determined by a wet weight/dry weight technique and Na+, K+ and Ca2+ contents were measured by inductive Couple Plasma-9000 at 6 h, 24 h and 48 h post-injection. Extravasation of Evan's blue (EB) into the brain was determined as an indicator of disturbance in the blood-brain barrier (BBB) and endothelial cells. Histologic studies were performed under a Leitz microscope and a Philips EM208s electron microscope. RESULTS: Dose-dependent and time-related increase of brain water was induced after tACPD (10, 50, 500 and 1000 nmol) injection. A significant increase in Na+ and K+ content but not in Ca2+ content was observed. EB extravasation showed no blue stain, indicating no increase in BBB permeability induced by tACPD-injection. Electron microscope study confirmed this finding and revealed remarkable swelling of astrocytes especially endfoot processes of astrocytes around capillaries at 6 h after tACPD-injection. In addition, all changes mentioned above occurred in both caudatum. CONCLUSION: These results indicate that activation of mGluRs by tACPD injected into the caudatum induced cytotoxic brain edema and interfered with astrocyte K+ buffering. This may provide new clues for therapeutic intervention. PMID- 11776059 TI - Multicenter clinical trial using an accelerated streptokinase regimen in patients with acute myocardial infarction. AB - OBJECTIVE: To observe the clinical efficacy and safety of intravenous thrombolytic therapy using an accelerated streptokinase (SK) regimen in acute myocardial infarction (AMI). METHODS: Data were collected from 40 hospitals during April 1996 to July 1997. Clinical therapeutic efficacy, five-week mortality, and adverse events were analyzed in 527 patients with AMI treated with an accelerated SK regimen (1.5 million IU within 30 min). RESULTS: The reperfusion rate of infarct-related arteries (IRAs) was 79.7% (421/528) assessed by clinical signs. The total mortality in the first 5 weeks was 6.6% (35/527). The incidence of allergic reactions and hypotension was 3.8% (20/528) and 4.2% (22/528), respectively. The incidence of bleeding was 2.7% (14/528), including cerebral bleeding 0.8% (4/528) and other major bleeding 0.8% (4/528). CONCLUSION: Intravenous accelerated SK therapy can markedly improve reperfusion rate without increasing adverse events such as bleeding, allergic reactions and hypotension. PMID- 11776060 TI - Molecular basis of behavioral recovery following spinal cord decompression: an immunocytochemical study. AB - OBJECTIVES: To examine whether the expression of choline acetyltransferase (ChAT), a marker for cholinergic neurons, and growth-associated protein (GAP-43), a marker for synaptogenesis, occurs differently following compression vs. decompression of spinal cord, and whether the reactions have any relationship with the time course of behavioral recovery. METHODS: A spinal cord compression model was studied quantitatively with an immunohistochemical method. The behavioral recovery of the rat was assessed by combined behavior score (CBS). RESULTS: The rebound in the ChAT-positive cell ratio was higher in decompressed cord than in compressed one. The time course of the change in the ChAT-positive cell ratio coincided with the recovery of CBS in the two models. Increased GAP-43 expression was found in the region of injured cord in the two models. Increased GAP-43 expression was partially parallel to the recovery of CBS, both in the decompression and continuous compression groups. CONCLUSIONS: The results indicate that there are ChAT reversible neurons in both the compressed and decompressed cord, the number of which is closely related to the recovery of behavior following cord injury. Synaptogenesis plays a limited role in behavior recovery. PMID- 11776061 TI - Diagnostic potential of mitochondrial DNA assessment in patients with optic neuropathy. AB - OBJECTIVE: To study the primary mutations of mitochondrial DNA (mtDNA) associated with Leber's hereditary optic neuropathy (LHON) in patients with optic neuropathy. METHODS: Seventy-nine patients with a variety of bilateral optic neuropathies were examined. Mutations at np3460, np11,778 and np14,484 of mtDNA were tested by PCR-restriction detection in peripheral blood DNA from 16 cases of clinically probable LHON, 44 cases of possible LHON, 2 cases of alcohol amblyopia, 4 cases of multiple sclerosis, 5 cases of autosomal dominant optic atrophy, 4 cases of primary open-angle glaucoma, 3 cases of spinocerebellar degeneration, and 1 case of ethambutol-induced optic neuropathy. RESULTS: The mutation at np11778 was identified in 31 cases (39.2%) to establish LHON, which consisted of: all 16 of clinically probable LHON cases, 13 cases (29.5%) of possible LHON, and 2 cases of alcohol amblyopia. The remaining 48 cases were negative for mtDNA mutations at np3460, np11 778, and np14,484. CONCLUSION: Assessment of mtDNA provides a useful diagnostic aid in the definition and exclusion of LHON, in particular family history-negative, otherwise undefined bilateral optic nerve inflammatory disease. PMID- 11776062 TI - Calcitonin gene-related peptide in Langerhans cells in psoriatic plaque lesions. AB - OBJECTIVE: To study the mechanism of stress exacerbating psoriasis and the involvement effect of neuropeptides in psoriatic pathogenesis, we investigated the expression and secretion of calcitonin gene-related peptide (CGRP) in psoriatic lesions, then identified the target cells of CGRP, the characters of CGRP positive dendrite cells and the source of CGRP in psoriatic plaque lesions. METHODS: Specific radioimmunoassay (RIA) and immunohistochemistry staining methods were used to determine CGRP secretive content and the target cells of CGRP in psoriatic plaque lesion tissue of vulgaris psoriasis. Double immunofluorenscence staining was done on psoriatic plaque lesion sections by first using rabbit anti-human CGRP antibody and mouse anti-human CD1a antibody, second using PE-conjugated anti-mouse immunoglobulin and FITC-conjugated anti rabbit immunoglobulin. Confocal laser microscope showed the psoriatic lesion sections. Then both digoxigenin labelled anti-sense and sense RNA probe of CGRP were synthesized to make sure the source of CGRP on the dendrite cells. The psoriatic lesion sections were studied by in situ hybridization. RESULTS: The content of CGRP in vulgaris psoriatic plaque lesions was higher than that of normal controls (P < 0.01). CGRP was also found on the dermal microvascular endothelial cells and the epidermal dendrite cells in psoriatic plague lesions. Further study showed that CGRP existed on the surface of epidermal CD1a + Langerhans cell in psoriatic plaque lesion. The CGRP mRNA expressed around the nucleus of the Langerhans cells in psoriatic lesion. CONCLUSIONS: The pathogenesis of psoriatic plaque lesions was closely related to the overexpression of neuropeptide CGRP. The CGRP contacted with the dermal microvascular endothelial cells and epidermal dendrite cells in psoriatic plaque lesion. The CGRP positive epidermal dendrite cell was CD1a + Langerhans cell. The Langerhans cell itself expressed CGRP mRNA. PMID- 11776063 TI - Effect of immunoglobulin G from patients with Graves' ophthalmopathy and interferon gamma in intercellular adhesion molecule-1 and human leucocyte antigen DR expression in human retroocular fibroblasts. AB - OBJECTIVE: To detect the expression of intercellular adhesion molecule-1 (ICAM-1) and human leucocyte antigen-DR (HLA-DR) on retroocular fibroblasts (RFs) by immunoglobulin G (IgG) from patients with Graves' ophthalmopathy (GO) and interferon gamma (IFN-gamma) and to study the possible mechanism of humoral immunity and cellular immunity in the pathogenesis of GO. METHODS: Purified IgG was obtained from 23 patients (GO 10, Graves' disease 9, toxic multinodular goiter 4) and 8 normal persons. Cytokine IFN-gamma and thyroid stimulating hormone (TSH) were incubated with normal human RF cultured in vitro. Antigen expression on RFs induced by stimulators was examined using immunofluoresence staining and a flow cytometer. RESULTS: RFs spontaneously expressed ICAM-1, but did not express HLA-DR. All IgGs from patients with GO and other thyroid diseases as well as from normal persons could not stimulate the expression of ICAM-1 on RFs. IFN-gamma and TSH significantly enhanced the expression of ICAM-1 in dose dependent manner (P < 0.05). Only IFN-gamma could stimulate RFs to express HLA-DR (P < 0.05). CONCLUSIONS: IgG from patients with GO did not stimulate the expression of ICAM-1 and HLA-DR on the surface of cultured normal human RFs. IFN gamma was the important factor for intiating and promoting autoimmune reactions in GO. We need to pay more attention to TSH, as it may possibly play a promoting role in the pathogenesis in GO. PMID- 11776064 TI - Effects of platelet activating factor antagonist (BN50739) on gut mucosal injury in acute severe pancreatitis in pigs. AB - OBJECTIVE: To study the role of platelet activating factor (PAF) in the pathogenesis of intestinal mucosal injury and endotoxin/bacterial translocation in acute severe pancreatitis (ASP) in pigs. METHODS: ASP was induced by intraductal injection of a mixture of sodium taurocholate and trypsin. BN50739, a specific antagonist of PAF, was given 30 min prior to the induction of ASP. Mucosal blood flow, mucosal myeloperoxidase (MPO) and malondialdehyde (MDA) were determined. Intestinal injury was observed microscopically. Portal blood endotoxin levels and the bacterial counts in the portal blood, intestinal lymph nodes and the pancreas were determined. RESULTS: Prior antagonism of PAF by BN50739 reduced intestinal injury, increased intestinal mucosal blood flow, and reduced blood levels of endotoxin and bacterial counts in the portal blood, mesenteric lymph nodes and pancreas. CONCLUSIONS: Intestinal mucosal injury developed in ASP. PAF is responsible for the injury. Antagonism of PAF by BN50739 can improve intestinal microcirculation and reduce the severity of intestinal mucosal injury, which may decrease endotoxin/bacterial translocation. PMID- 11776065 TI - Risk factors for development of diabetes mellitus in women with a history of gestational diabetes mellitus. AB - OBJECTIVE: To determine whether diabetes recurs in their later life when women have a history of gestational diabetes mellitus (GDM) or abnormal glucose tolerance test (impaired glucose tolerance, IGT). METHODS: Three groups of women were investigated at 5-10 years postpartum. GDM group (n = 45) had been diagnosed as having GDM in their previous pregnancy. IGT group (n = 31) had a history of abnormal glucose tolerance test during previous pregnancy. Normal control group (n = 39) was normal previous pregnant population. Their previous obstetric and medical histories were thoroughly reviewed. Fasting plasma glucose (FPG) and oral glucose (75 g) tolerance test (OGTT) were repeated in all women. RESULTS: Diabetes mellitus (DM) was diagnosed in 33.3% of patients in the GDM group, while in 9.7% in the IGT group and in 2.6% in the normal control group. Incidence of recurring DM in later life was significant higher in the GDM group (P = 0.017). When one or more blood glucose values exceeding WHO criteria for diagnosis of diabetes in their previous pregnancy, the incidence of DM in later life was 60% (3/5, including GDM in women having four abnormal OGTT values), 41.7% (5/12) in women having three, 25% (7/28) in women having two and 9.7% (3/31) in women having one. The women with DM, also with a history of GDM and abnormal OGTT in previous pregnancy, tends to have a high pregnant body mass index (BMI > 25 kg/m2). CONCLUSION: The women suffering from GDM during previous pregnancy have a high risk of recurrence DM. Two or more abnormal OGTT values during pregnancy, blood glucose level exceeding the maximal values at 1 and 2 hours after oral glucose loading and high pregnant BMI are concluded to be useful factors in predicting the recurring DM in their later life. PMID- 11776066 TI - Myocardial contraction maps using tissue Doppler acceleration imaging. AB - OBJECTIVE: To evaluate the tissue Doppler acceleration imaging (TDAI) data which can be used to determine the intramural site of origin of myocardial contraction in response to electrical stimulation. METHODS: Six open-chest pigs with left ventricle (LV) pacing were evaluated with TDAI. An epicardial surface scanning method was used to collect short-axis views of the left ventricle. The electrode was implanted from the epicardium through the anterior free wall to an intramural position. RESULTS: During pacing, the intramural onset of myocardial acceleration occurred within 33 ms after electrical stimulation and always surrounded the embedded subendocardial end of the pacing needle. The observed short-axis diameter of the area of initial myocardial acceleration ranged from 2.9 mm to 5.0 mm (4.2 +/- 0.9 mm, n = 6). The onset of myocardial acceleration allowed appreciation of the initial intramural myocardial contraction. The spatial size and acceleration magnitude of the initial myocardial acceleration distribution were irregular. CONCLUSION: Two-dimensional myocardial acceleration mapping can show the intramural site of origin of myocardial contraction in response to paced electrical stimulation. The location of myocardial acceleration conformed to the site of initial electrical stimulation. The delay to the earliest regional myocardial contraction, 33 ms after paced electrical stimulation, was related to the frame rate of image acquisition. PMID- 11776067 TI - Effect of selenium on human myocardial glutathione peroxidase gene expression. AB - OBJECTIVE: To examine the role of selenium (Se) in the expression and activity of selenium-dependent cellular glutathione peroxidase (GPX-1). METHODS: 46 patients with atrial septal defect or ventricular septal defect were separated into two groups, a control group (23 cases) and a Se supplementation group (23 cases). The Se supplementation group received 400 micrograms selenium per day for 7 days before surgery. We used biochemical techniques, atomic absorption, RT-PCR and cDNA sequence testing methods to evaluate and compare the changes during ischemia/reperfussion (I/R) in myocardial melondialdehyde (MDA) level, GPX activity and gene expression level, GPX cDNA nucleotide sequence, selenium and calcium and magnesium concentration. RESULTS: Before ischemia, taking selenium for 7 days did not change the selenium concentration in either plasma or blood cells in either group. The GPX mean activity level in the selenium group was slightly lower than that in the control group, and the MDA level was equal in both. After 30 minutes of reperfusion, the Se level in plasma and blood cells remained constant, while the myocardial Se concentration and GPX gene expression in the Se group increased significantly. The MDA level in the Se group reduced 4.2%, compared to an 8.2% rise in the control group. The mean level of GPX activity in the Se group was slightly lower than that in the control group. Both pre- and post-myocardial reperfusion, the Se group had a higher rate of myocardial GPX gene expression, and the nucleotide sequence was normal. These results indicate that supplementing Se is not likely to enhance myocardial GPX activity, but it could increase the GPX gene expression level, and thereby enhance the Se patients' myocardial antioxidant level during I/R, allowing free radicals to be scavenged as soon as they are generated. CONCLUSION: Se supplementation could increase myocardial selenium content and improve GPX gene expression during I/R, and in this way defend against free radical peroxide damage to the myocardium. PMID- 11776068 TI - The potential role of PDGF, IGF-1, TGF-beta expression in idiopathic pulmonary fibrosis. AB - OBJECTIVE: To identify the role of cytokines involved in the development of lung fibrosis in patients with idiopathic-pulmonary fibrosis (IPF). METHODS: Proteins and gene expression of platelet-derived growth factor (PDGF)-A and -B, insulin like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-beta) were measured in alveolar macrophages and open lung biopsies from patients with IPF using immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, IGF-1, TGF-beta were localized in alveolar macrophages. Evaluation of open lung biopsies from patients with IPF showed that IGF-1 was prominently present in pulmonary vessel walls in fibrotic lesions. PDGF and TGF-beta proteins were localized to hyperplastic bronchio-alveolar epithelial cells, alveolar macrophages, fibroblasts, vascular smooth muscle and endothelial cells. Our in situ hybridization results were consistent with that of immunohistochemistry except that PDGF-A and TGF-beta mRNA transcripts were not detected in bronchoalveolar epithelial cells. CONCLUSION: These observations suggest that (1) alveolar macrophages play key roles not only in inflammation but also in the fibrotic process by releasing PDGF, IGF-1 and TGF-beta; (2) IGF-1 could be responsible for angiogenesis in IPF; (3) PDGF, TGF-beta are associated with fibroplasia and the deposition of extracellular matrix, as well as vessel remodeling and epithelial cell repopularization. PMID- 11776069 TI - Kinetic study of eosinophil apoptosis and its relationship to Th2 cytokines in asthmatic murine model. AB - OBJECTIVE: To investigate the significance and regulatory mechanism of eosinophil apoptosis in asthmatic airway inflammation using an animal models, as well as its relationship to IL-5 and IL-10. METHODS: An animal model of asthma was established by ovalbumin (OVA) sensitizing-challenging BALB/C mice. At seven points in the time course after challenge, bronchoalveolar lavage (BAL) was performed to obtain BAL cells. Levels of two Th2 cytokines, IL-5 and IL-10 were detected by ELISA. A double label technique combining CD15 with CD49d was used to distinguish eosinophils from other cell types. Cell apoptosis was assayed by PI stain using a flow cytometer. RESULTS: Eosinophil apoptosis was identified and a two-phase elevation of apoptosis percentages was observed, although no significant difference was found between average apoptosis in the asthmatic group and that in the control. Analysis of kinetic changes of eosinophil apoptosis and cytokine levels revealed a negative correlation between apoptosis percentages and levels of IL-5, and a closer correlation between apoptosis percentages and the IL 5/IL-10 ratio. Dexamethasone pretreatment markedly reduced IL-5 levels in BAL, elevated eosinophil apoptosis percentages, but had no effect on IL-10 levels. CONCLUSION: Eosinophils underwent apoptosis in asthmatic airways. Equilibrium between IL-5 and IL-10 not only regulated eosinophil infiltration, but also modulated cell apoptosis. PMID- 11776070 TI - Vitamin D receptor gene polymorphism in postmenopausal women of the Han and Uygur nationalities in China. AB - OBJECTIVE: Polymorphism in vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass. Its role within various ethnic populations is not clear. The purpose of this study was to determine the frequencies of VDR genotypes in the Han and Uygur nationalities in China. METHODS: We analyzed the polymorphism of Bsm I restriction enzyme by PCR RFLP technique in 162 healthy postmenopausal women of the Han nationality and 50 healthy postmenopausal women of the Uygur nationality in China. The genotype frequencies of VDR were calculated using Hardy-Weinberg equilibrium formula. RESULTS: In the Han nationality, the bb, Bb, and BB genotype accounted for 91.36%, 8.64% and 0%, respectively. In the Uygur nationality, frequencies were 74.00%, 18.00% and 8.00%, respectively. CONCLUSION: There was a significant difference between the Han and Uygur nationalities in the frequency distribution of VDR genotype (P < 0.01). Compared with the Caucasian population in the United States, Australia and France, there was a similar value to Uygur nationality in the BB genotype. This investigation gave us further evidence on the different etiopathology of osteoporosis in various ethnic groups. PMID- 11776071 TI - Effect of anti-P-selectin monoclonal antibody on renal ischemia/reperfusion injury in rats. AB - OBJECTIVE: To explore the effect of anti-P-selectin monoclonal antibody (mAb) on renal ischemia/reperfusion (I/R) injury in rats. METHODS: Renal function, renal histopathological changes, plasma P-selectin levels and renal P-selectin protein and mRNA expression were studied in a renal I/R injury rat models. Biochemical measurement, ELISA, Immunohistochemistry and Nested RT-PCR were used. RESULTS: Renal function insufficiency and renal histopathological damage were much less in the anti-P-selectin mAb-treated group than the saline-treated group. Plasma P selectin levels were lower and renal P-selectin protein and mRNA expression were down-regulated in the former group. CONCLUSION: Anti-P-selectin mAb might be an efficient approach for the treatment of renal I/R injury. PMID- 11776072 TI - Comparison of Botox with a Chinese type A botulinum toxin. AB - OBJECTIVE: To confirm and compare the therapeutic efficacies and remote effects of a Chinese type A botulinum toxin (CBTX-A, Lanzhou Biological Products Institute, China) and Botox (Allergan Inc., USA) for focal dystonia and muscle spasm. METHODS: Prospective open study was conducted over 4 years for focal dystonia and muscle spasm. We enrolled 785 patients: 192 were injected with Botox and 593 with CBTX-A. They were followed for 3 to 48 months. Meanwhile single fiber electromyography (SFEMG) was performed in a subset of 40 patients before, 2 3 weeks, 5-8 weeks and 4-5 months after injection of Botox or CBTX-A. RESULTS: There were no significant differences in clinical effects from two preparations, including the latency of response, maximal benefit and duration of improvement. The dose of the Chinese preparation which produced effects similar to Botox was higher. A significant increase in jitter was demonstrated 2-3 weeks after injection in both groups and fiber density values increased at the same time or later and remained 4-5 months after injections. CONCLUSION: Both preparation are safe and effective treatments for patients with focal dystonia and muscle spasm. They both have subclinical effects on neuromuscular transmission of remote uninjected muscles. The Chinese preparation is a little less powerful but much cheaper than Botox. PMID- 11776073 TI - Carcinoma of the lung and multiple primary tumors. AB - OBJECTIVE: To assess the incidence of multiple primary malignancies combined with lung and other organs. METHODS: All patients who were consecutively treated for lung cancer from December 1964 to December 1992 were retrospectively analyzed regarding the occurrence of simultaneous primary tumor elsewhere in the body. RESULTS: Of 1019 patients reviewed, 21 (2.1%) had associated carcinoma of other organs. In these 21 patients, the incidence of associated aerodigestive tract cancer was 71% and cancer of other organs was 29%. Five patients had simultaneous cancer with the lung cancer and 16 metachronous lung cancer associated with cancer of other organs. CONCLUSIONS: Multiple primary tumors in patients with carcinoma of the lung is not a rare phenomenon. Surveillance programs for detection of second primary tumors should focus on this group of patients. Surgeons should be aware of the possibility of double cancer, and the patient's condition and stage of the carcinoma must be taken into consideration in the determination of operative indications and method. PMID- 11776074 TI - Expression and significance of urokinase-type plasminogen activator in human gliomas. AB - OBJECTIVE: To investigate the expression and clinical significance of urokinase type plasminogen activator (uPA) in human gliomas. METHODS: mRNA and protein expressions of uPA were examined by Northern blot hybridization and immunohistochemical method in 43 cases of gliomas and 5 cases of normal brain tissues and their relationship to clinical indexes was comprehensively analyzed. RESULTS: All tissues expressed the 2.5 kb transcript of uPA mRNA. The uPA mRNA level in high-grade gliomas was considerably higher than that in low-grade gliomas and normal brain tissues (P < 0.01). Levels of uPA mRNA expression in tumor tissues with recurrence during 18 postoperative months and a survival period less than 3 years, were significantly higher than counterparts (P < 0.01). uPA mRNA expression was strongly correlated with the microvessel quantity (MVQ) in gliomas (r = 0.56, P < 0.01). uPA protein was mainly distributed in tumor cells and endothelial cells of glioblastomas and anaplastic astrocytomas. CONCLUSION: Expression of uPA is associated with the malignant progression, invasion and angiogenesis of gliomas, and it may play a critical role in the recurrence and prognosis of gliomas. PMID- 11776075 TI - Stress-relaxation plates and the remodeling of callus and cortex under the plate in rabbits. AB - OBJECTIVE: To study the influence of a stress-relaxation plate on the remodeling of callus and cortex under the plate. METHODS: The bilateral tibia diaphysis of New Zealand rabbit were osteotomized and fixed with stress-relaxation plate (SRP) and rigid plate (RP), respectively. Polarized light microscopy and transmission electron microscopy (TEM) were used to study the remodeling of callus and the cortex under the plate from 4 to 24 weeks postoperatively. RESULTS: Polarized light microscopy: the structural changes of callus and cortex beneath the plate are similar in the SRP and RP groups at the early postoperative stage, manifesting an alignment disorder of collagen fibers with a weak birefringence in the callus and absorption cavities in the cortex under the plate. After the twelfth postoperative week, the SRP group showed callus starting to transform to lamellar bone and absorption cavities in the cortex under the plate becoming smaller. By contrast in the RP group the absorption cavities in the callus and cortex under the plate became larger and the whole layer of cortex was cancellated. TEM: the active osteoclasts appeared in both SRP and RP groups in the period from 4 to 8 weeks postoperatively. In the SRP group, many functionally active osteoblasts could be seen on the surface of the bone, while in the RP group, the osteoblasts were not very active. By 24 weeks postoperatively, the shape of osteocytes were normal but the number of the osteoclasts were small in the SRP group. In the RP group, the osteoclasts became more active and osteocytic osteolysis was manifested. CONCLUSIONS: Fixation with SRP not only enhanced callus remodeling, but also abated the degree of osteoporosis in the cortex under the plate. This approach may lead to an improved osteosynthetic apparatus. PMID- 11776076 TI - Operative laparoscopy versus laparotomy for the management of ectopic pregnancy. AB - OBJECTIVE: To compare the surgical managements for ectopic pregnancy. METHODS: In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients. RESULTS: The change from laparotomy to laparoscopic treatment was significant. The success rates of salpingostomy and salpingectomy under laparoscopy or laparotomy were 100%. No serious complications occurred. The operation time and length of hospital stay for laparoscopic salpingostomy were shorter than those for laparotomy with salpingostomy. CONCLUSION: Laparoscopic salpingostomy and laparoscopic salpingectomy are better than laparotomy in the treatment of ectopic pregnancy. PMID- 11776077 TI - Effect of prenatal tetrandrine therapy on pulmonary vascular structural remodeling in the nitrofen-induced CDH rat model. AB - OBJECTIVE: To examine the effects of prenatal tetrandrine (Tet) therapy on pulmonary arterial structural remodeling in nitrofen-induced congenital diaphragmatic hernia (CDH). METHODS: CDH was induced in fetal rats by maternal administration of 100 mg nitrofen by gavage on day 9.5 of gestation (term, day 22). Control animals received olive oil (OO). Tet (24 mg/kg per day) or normal saline (NS) was given by gavage every day from 16 to 20 days of gestation, and fetuses were delivered by caesarean section on day 21.5. Lung sections from 3 fetuses in each group were studied. The number of vessels were calculated, the external diameter (ED), medial wall thickness (MT), percent of medial wall thickness, and wall structure were evaluated by image analysis software. RESULTS: In the pre-acinar arteries, CDH-NS pups had a significantly increased %MT compared with the OO-NS group (P < 0.05), while CDH-Tet animals had a reduced %MT compared with the CDH-NS rats (P < 0.05). Similar results were seen in the intra acinar level. Significant differences were observed between CDH-NS animals and OO NS controls in the percentage of muscularized intra-acinar blood vessels (P < 0.001). Tet-treated CDH pups had a reduced percentage of muscularized intra acinar arteries compared with CDH-NS animals. CONCLUSIONS: Medial hypertrophy is present in both the pre-acinar and intra-acinar arteries in the nitrofen-induced CDH rat model. Tet treatment inhibits medial hypertrophy and reduces the percentage of muscularized intra-acinar vessels. Prenatal Tet therapy may be efficacious in reducing the risk of PH in human newborns with CDH. PMID- 11776078 TI - Deletion of chromosomes 9p and 17 associated with abnormal expression of p53, p16/MTS1 and p15/MTS2 gene protein in hepatocellular carcinomas. AB - OBJECTIVE: Fifteen loci on chromosome 9p and 17 were analyzed to clarify the involvement of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) in Chinese patients positive for hepatitis B (HBV) and/or hepatitis C (HCV) infection. Expression of tumor suppressor genes (TSG) of p53, p16, and p15 gene was found to correlate with a deletion of these genes. METHODS: Immunohistochemistry and PCR-based microsatellite polymorphism analysis techniques were used. RESULTS: A high frequency of LOH was detected on chromosome 9p24 at locus D9S54 (61.8%) and 9p21, concentrated at loci D9S1747 (52.4%) and D9S1752 (51.8%). On chromosome 17, high frequent LOH was concentrated on 17p at the p53 gene locus (53.8%) and locus D17S520 (52.8%). p53 protein expression was increased in HCC, which correlated with p53 gene loss. Expression of p16 and p15 protein decreased in HCC when LOH occurred at locus D9S1752 (p15 gene locus) or at locus D9S1747 and D9S1748 (p16 gene is located between these 2 loci). LOH at the p53 gene and p15 gene loci was closely associated with HBV and HCV co infection in HCC. No significant relationship between LOH and HCC clinico pathological outcomes was observed. CONCLUSION: High frequency LOH occurs on chromosomes 9p and 17 in HCC in Chinese patients. Such sites may contain several putative tumor suppressor genes critically involved in the development and/or progression of HCC. Deletion of p53, p16, or p15 tumor suppressor genes may cause abnormal expression of the protein product of these genes. HBV and/or HCV infection may be closely associated with LOH p53 and/or p15 gene expression. PMID- 11776079 TI - c-myc gene inactivation during induction of nasopharyngeal carcinoma cells with retinoic acid. AB - OBJECTIVE: To investigate the effects of retinoic acid (RA) on the growth, morphology, oncogene expression and regulation of nasopharyngeal carcinoma cells. METHODS: Nasopharyngeal carcinoma cell line (HNE1) was induced by RA. The RA treated and control cells were established and cellular morphology and growth patterns were defined. Oncogene expression and regulation were detected by Northern hybridization and DNase-I hypersensitive site analysis. RESULTS: RA markedly inhibited cell growth. The growth of HNE1 cells was reduced to 50% of the control level on the 4th day of RA (10(-4) mol/L) treatment. After 4 days of treatment, the rapidly growing polygonal cells were reversed into a slow growing phenotype, with flattened morphology similar to fibroblast-like cells. Northern hybridization showed that c-myc and c-Ha-ras expression was high in HNE1 cells and undetectable in normal blood cells. c-myc was down-regulated at 48 h of RA treatment. In contrast, the c-Ha-ras was not affected. DNase I hypersensitive site analysis detected changes in the regulatory elements of c-myc and c-Ha-ras genes. 5 hypersensitive sites were found in the c-myc of HNE1 cells, while 3 hypersensitive sites disappeared upon HNE1 induction. However, only 1 hypersensitive site was found in c-Ha-ras of RA treated cells and controls. In normal peripheral white blood cells, no DNase I hypersensitive sites were found in the inactive c-myc and c-Ha-ras gene. CONCLUSION: RA can induce differentiation in a nasopharyngeal carcinoma cell line at high concentration of RA; HNE1 shows some similar patterns of DNase I hypersensitive sites with the common one in other types of cells expressing c-myc. The repression of c-myc expression with induction is accompanied by the loss of 3 DNase-I hypersensitive sites; c-myc has more than one inactive conformation. PMID- 11776080 TI - Continuous long-term albendazole therapy in intraabdominal cystic echinococcosis. AB - OBJECTIVE: To assess the therapeutic effects of long-term albendazole therapy in intraabdominal cystic echinococcosis. METHODS: Fifteen patients with a total of 45 cysts were treated with albendazole with dosage regimen of 20 mg.kg-1.d-1 for an average of 2.5 years. Repeated CT and ultrasound scannings (US) were performed after the end of therapy. The duration of follow-up was 3.6 years on average. The number, size and morphology of cysts were compared before and after treatment. RESULTS: The hydatid cysts were classified according to location and CT patterns into hepatic simple cysts, hepatic cysts with daughter cysts, hepatic/abdominal cysts and splenic cysts. The hepatic simple cysts responded most favorably to albendazole therapy, with an overall cure rate of 88.7%. The disappearance of cysts was observed in 43.0% of cases (15/35). Sixteen cysts (45.7%) became solidified or calcified, among which 8 cysts were completely calcified, 6 showed egg shell-like calcification of the cystic walls, and 2 showed solidification and calcification of cyst contents. Four patients had large hepatic cysts containing daughter cysts; the daughter cysts all disappeared after treatment, but one patient relapsed with the reappearance of daughter cysts at 4-year follow-up. Two splenic cysts also calcified. Two patients had peritoneal cysts; one calcified and the other one reduced in size. Among 15 patients treated, 9 were cured and 6 were improved. There was no serious toxic reactions with continuous long-term therapy in a small series of patients. CONCLUSIONS: Continuous long-term albendazole treatment of intraabdominal cystic echinococcosis is safe and effective in the treatment of hepatic simple cysts, and some daughter cysts, peritoneal secondary cysts and splenic cysts. No serious toxic reactions were found. PMID- 11776081 TI - Factors influencing the expression of Fas and Fas ligand on newborn murine keratinocytes and fibroblasts. AB - OBJECTIVE: To investigate the expression of Fas, FasL mRNA and proteins on keratinocytes and fibroblasts, and the influence by retinoid acid (RA) and dexamethasone (Dex). METHODS: RNase protection assay and flow cytometry were used. RESULTS: Fas mRNA was expressed on neonatal murine keratinocytes and was up regulated by all-trans retinoid acid and down-regulated by Dex. RA and Dex also increased the Fas protein expression on keratinocytes. Newborn murine keratinocytes express FasL mRNA, which was up-regulated by RA and Dex, while its protein expression was moderately induced by RA. Newborn murine fibroblasts also expressed Fas and FasL mRNA, which were up-regulated by the RA and Dex. CONCLUSIONS: The results indicated that RA and Dex might regulate apoptosis of keratinocytes and fibroblasts via the Fas-FasL system. PMID- 11776082 TI - Hyperbaric oxygen preconditioning induces neuroprotection against ischemia in transient not permanent middle cerebral artery occlusion rat model. AB - OBJECTIVE: This study was designed to determine if repeated hyperbaric oxygen (HBO) exposure induces ischemic tolerance in focal cerebral ischemia. METHODS: Sixty male SD rats were used in this study. Thirty animals underwent transient middle cerebral artery occlusion (MCAO) and the other thirty permanent MCAO model. The rats were randomly allocated to 3 sub-groups: control group (n = 10), HBO-3 group (n = 10), and HBO-5 group (n = 10). The animals in HBO-3 and HBO-5 groups received 1 hour hyperbaric oxygenation at 2.5 atmosphere absolute (ATA) in 100% oxygen every day for 3 and 5 days, respectively. The animals in the control group received sham treatments. 24 hours after the last HBO, transient MCAO (120 min) and permanent MCAO were induced by introducing a 3-0 nylon monofilament suture through internal carotid artery based on the Koizumi technique. The neurological outcome was evaluated until 24 hours after reperfusion in transient MCAO rats and ischemia in permanent MCAO rats. The infarct volume was then assessed by TTC staining. RESULTS: In transient MCAO rats, the neurological outcome in both the HBO-3 and HBO-5 groups was better than that of the control group (P < 0.05 and 0.001). The infarct volume decreased from 171.5 +/- 113 mm3 to 40.6 +/- 49.9 mm3(P < 0.05) in the HBO-3 group and 16.2 +/- 28.8 mm3(P < 0.01) in the HBO-5 group. There were no significant differences in neurological outcome and infarct volume among the three groups in permanent MCAO rats. CONCLUSIONS: The present study demonstrated that HBO preconditioning can induce ischemic tolerance in transient not permanent MCAO rats in a "dose-dependent" manner. PMID- 11776083 TI - Propofol combined with diazepam synergistically potentiates the GABA-activated chloride current in rat sensory neurons. AB - OBJECTIVE: To investigate the effect of propofol combined with diazepam on the gamma-aminobutyric acid (GABA)-activated chloride current (IGABA) evoked in rat sensory neurons. METHODS: Whole cell patch clamp recordings were made from cultured rat dorsal root ganglionic neurons. GABA (3 mumol/L) was applied by pressure ejection. The anesthetics were dissolved in the external solution and given by the "Y-tube" method. RESULTS: Co-application of propofol (0.3-3 mumol/L) and diazepam (100 nmol/L) potentiated the IGABA which was significantly larger than the sum of that potentiated by drug alone. Diazepam (100 nmol/L) shifted the concentration-response curve for the IGABA potentiation induced by propofol to the left in a parallel fashion. The EC50 value for propofol was decreased by diazepam from 7.6 +/- 1.8 mumol/L to 3.9 +/- 1.1 mumol/L (n = 9). CONCLUSIONS: Our results suggest that propofol combined with diazepam synergistically potentiates the IGABA. Diazepam-induced increase in the apparent binding affinity of propofol for the GABAA receptors is likely responsible for a clinical synergistic hypnotic action during co-application with propofol and diazepam. PMID- 11776084 TI - An investigation of immunocompetence substances in normal gingival and periodontitis tissue. AB - OBJECTIVE: To investigate the effects of nitric oxide (NO), endothelin (ET), substance P (SP) and calcitonin gene-related peptide (CGRP) immunocompetence substances and their relationship to chronic periodontitis. METHODS: Immunohistochemical aod histochemical staining methods were used to detect the expression of the NO synthase (NOS), ET, SP and CGRP levels in 20 patients with chronic periodontitis and 20 healthy subjects as control. RESULTS: Quantitative analysis by Quantimat 970 showed that NOS and ET in periodontitis tissue increased significantly (P < 0.01), particularly the content of ET in comparison with healthy subjects. The intergroup expression of SP and CGRP showed no remarkable changes. CONCLUSION: Our results demonstrate that the level of NOS and ET were significantly increased in periodontic tissue, which may diminish the blood supply and influence the periodontal tissue causing tissue damage. Our study suggests that immunocompetence substances NO and ET are closely associated with periodontitis and may play an important role in the disease. PMID- 11776085 TI - The role of c-myc in regulating mdr1 gene expression in tumor cell line KB. AB - OBJECTIVE: To investigate the relationship between c-myc expression and mdr1 regulation in multidrug resistance (MDR) tumor cell line KBv200. METHODS: A DNA sequence encoding the ribozyme gene was incorporated into a eukaryotic expression vector (pH beta Apr-1 neo) and transfected into the cell line KB, which is resistant to vincristine and expresses the MDR phenotype. The changes of c-myc protein, P-glycoprotein (P-gp) and c-myc mRNA in the KB cell line were assessed before and after treatment with anti-mdr1-ribozyme using immunohisto-chemistry, flow cytometry and semi-quantitative RT-PCR methods. RESULTS: The results demonstrate elevated levels of c-myc mRNA and c-myc protein as well as P-gp in KBv200 cells which are resistant to vincristine (VCR), compared to these of the KB cell which is not resistant to VCR. The expression of c-myc protein, P-gp and c-myc mRNA in the multidrug resistant cell, KBv200, displayed higher than that in the sensitive cell, KB. However, after reversing the multidrug resistance phenotype by anti-mdr1-ribozyme, the level of c-myc protein, P-gp and c-myc mRNA expression showed significant down-regulation in KBv/5 mR3, without difference in KB/5 mR3 and KB. CONCLUSION: The results of our study suggest that there is a close relationship between c-myc gene and mdr1 gene. c-myc may be involved in regulating the expression of mdr1. PMID- 11776086 TI - Hepatocellular adenoma and focal nodular hyperplasia: a series of 24 patients with clinicopathological and radiological correlation. AB - OBJECTIVE: To investigate two rare benign lesions, hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), and evaluate differential diagnosis. METHODS: Twenty-four consecutive patients with presumed HCA and FNH were studied at the Liver Cancer Institute from January 1996 to May 1999. Preoperative assessment included clinical evaluation, symptoms and laboratory tests. New imaging techniques were prospectively appraised in addition to usual techniques. All had hepatic resections and follow-up. Histologic examination of surgical specimens was obtained in all cases. RESULTS: In every instance, FNH was an incidental finding. FNH consists of nodular aggregates of cytologically normal hepatocytes with foci of intranocular bile duct proliferation. In this series, patients with HCA had larger tumors and more often were symptomatic but the occurrence was unrelated to oral contraceptive steroids (OCS) usage. Intralesional hemorrhage or necrosis is common, and was seen in 75% of cases. The best imaging procedure in the diagnosis of FNH was MRI. Color Doppler US was a useful adjunct, but CT lacked specificity, making histological diagnosis mandatory. All patients underwent tumor resected were tumor--free during the follow-up. CONCLUSIONS: FNH is a distinct histopathologic entity, and is distinguishable from HCA. FNH is a hyperplastic response by the liver parenchyma to a pre-existing arterial malformation. HCA is a liver neoplasia and has the potential of malignant transformation to HCC. Based on these findings, we believe that if the clinical suspicion of HCA or FNH is strong, resection is usually the best approach if technically feasible and histologic diagnosis is mandatory. PMID- 11776088 TI - Subcutaneous and brain abscesses caused by Nocardia farcinica in China. PMID- 11776087 TI - Anaerobic bacteria and intrahepatic stones: detections of Clostridium sp. and Bacteroides fragilis. AB - OBJECTIVE: To detect anaerobic bacteria Clostridium sp. and Bacteroides fragilis in intrahepatic stones by molecular genetic method. METHODS: DNA was extracted from 59 stone samples and subjected to polymerase chain reaction (PCR) amplification targeting the 16S rRNA gene of Clostridium sp. and the glutamine synthetase gene of Bacteroides fragilis. Single-strand conformational polymorphism (SSCP) analysis was performed to identify the Clostridium sp. RESULTS: 16S rRNA gene sequences for Clostridium sp. were identified in 49 stones (83%, 49/59). The two most common groups were detected in 19 (41%) and 17 (37%) of the 46 samples using SSPC analysis, and 25/59 (42%) stones were tested positive for Bacteroides fragilis. CONCLUSIONS: Anaerobes such as Clostridium sp. and Bacteroides fragilis present in intrahepatic stones and may play a role in stone formation. PCR is a useful technique to detect fastidious pathogens, which are difficult to culture. SSCP of PCR products is a rapid method in differentiating bacterial species. PMID- 11776089 TI - Current status of nuclear medicine in China. PMID- 11776090 TI - Radionuclide techniques for evaluating dilated cardiomyopathy and ischemic cardiomyopathy. AB - OBJECTIVE: To assess the clinical significance of radionuclide techniques in evaluating dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (CAD-CM). METHODS: 28 patients with DCM and 55 patients with CAD-CM were studied. All patients underwent 99mTc-MIBI myocardial perfusion SPECT and 18F-FDG myocardial metabolic PET. 78 patients had 99mTc-RBC radionuclide ventriculography and 68 patients had coronary angiography. RESULTS: The results of 23 patients (82%) with DCM showed mild and non-segmental distribution perfusion abnormalities. 52 patients with CAD-CM (95%) showed perfusion abnormalities that distributed along the coronary vessel territories. Significant perfusion defects were found in 4 patients with DCM (14%) and 45 patients with CAD-CM (82%) (P < 0.01). The average perfusion score was 4.5 +/- 2.6 in DCM and 9.6 +/- 2.5 in CAD-CM and the area of diminished perfusion was significantly smaller in DCM than in CAD-CM (P < 0.001). Two patients with DCM and 18 patients with CAD-CM had metabolic defects. The patterns of perfusion/metabolic imaging showed mismatch in most patients with CAD CM but match in most patients with DCM. The LVEF in patients with DCM and CAD-CM was both decreased but the decreases were not statistically different between DCM and CAD-CM. The RVEF in patients with DCM was significantly lower than that in patients with CAD-CM (32.4% +/- 13.9% vs 40.9% +/- 15.4%, P < 0.05). CONCLUSION: The radionuclide techniques are helpful for distinguishing DCM from CAD-CM. The segmental perfusion abnormality and RVEF are the most important factors for differentiation of DCM from CAD-CM. PMID- 11776091 TI - Clinical application of radioimmunoimaging with 99mTc-BDI-1 in the diagnosis of bladder cancer. AB - OBJECTIVE: To evaluate the clinical application of radioimmunoimaging (RII) with 99mTc-BDI-1 in the diagnosis of bladder cancer. METHODS: 32 patients with bladder cancer and 5 with normal bladder were studied. RII was performed 1 hour after intravesical administration of 111-222 MBq 99mTc-BDI-1 followed by washing out and perfusing bladder with 50 ml PBS. The radioactivity ratio of target over background (CT/CB) was calculated. RESULTS: The radiochemical purity of 99mTc-BDI 1 was greater than 95%. RII showed radioactive accumulation area for most of bladder cancers but no radio-active concentration for normal bladder. The sensitivity and specificity were 91.7% and 81.8% respectively with the assignment of the positive criterion of CT/CB > or = 1.40. There was no statistical difference in sensitivity between tumors with diameters > or = 1 cm (1.0-4.2 cm) and < 1 cm (0.2-0.8 cm). CT/CB was related to the pathological grade (G1-G3) of the tumor. CONCLUSIONS: RII by intravesical administration provides a new noninvasive method for the diagnosis of bladder cancer in morphology and in nature of tumor with high sensitivity and specificity. It may be used for the early diagnosis of bladder cancer, follow-up after surgery, and diagnosis of in situ tumor. PMID- 11776092 TI - 99mTc-MIBI and 99mTc-MDP scintimammography for detecting breast carcinoma. AB - OBJECTIVE: To assess the value of scintimammography with both 99mTc-MIBI and 99mTc-MDP in detecting breast cancer. METHODS: A total of 35 women with clinical findings of suspicious breast lesions were studied with both 99mTc-MIBI and 99mTc MDP scintimammography. All patients underwent surgery within one week and the final diagnostic results (histopathological) were obtained. RESULTS: Eighteen of 35 abnormalities of breast were pathologically confirmed as breast cancer and 17 as benigN lesions. In this group of patients studied, the sensitivity, specificity and accuracy of 99mTc-MIBI scintimammography were 77.8%, 88.2% and 82.9%, respectively and those of 99mTc-MDP scintimammography were 72.2%, 88.2% and 80.0%, respectively. There was no significant difference between 99mTc-MIBI and 99mTc-MDP scintimammography. CONCLUSION: This study showed the high diagnostic accuracy of both 99mTc-MIBI and 99mTc-MDP scintimammography in detecting breast cancer. Both can be used as non-invasively assess breast cancer invasiveness before surgery. PMID- 11776094 TI - Comparative study of D2 receptors and dopamine content in striatum before and after electro-acupuncture treatment in rats. AB - OBJECTIVE: To evaluate the change in D2 receptors and their relationship with dopamine (DA) content in experimental hemi-parkinsonism rats before and after electro-acupuncture (EA) treatment. METHODS: 125I-IBZM D2 receptor cerebral autoradiographic analysis, HPLC-ECD detection of DA and its metabolites, homovanillic acid (HVA), 3, 4-dihydroxyphenylacetic acid (DOPAC) were used to study their levels in striatum in pre-EA, EA and EA control group. RESULTS: The DA, HVA and DOPAC levels in striatum of the lesioned side in the EA group were elevated compared to the pre-EA and EA control group (P < 0.05). For the EA group, the striatum/cerebellum 125I-IBZM uptake ratio of the lesioned side was 8.04 +/- 0.71, (29.34% +/- 4.83%) more than that of the contralateral side (P < 0.05), while no significant difference was observed as compared with that in the pre-EA group (8.09 +/- 0.52, 30.12% +/- 4.53%, higher than that of the intact side P > 0.05). It was lower than the EA control group (8.61 +/- 0.63, P < 0.05), and the latter was (38.63% +/- 3.71%) higher than that in its contralateral side (P < 0.05). CONCLUSION: 6-OH-DA lesions in the substantia nigra and ventral tegmental areas induce an up-regulation of striatal D2 binding sites. EA treatment could elevate the DA level of the lesioned side striatum and prevent D2 receptor up-regulation in rats with experimental hemiparkinsonism. PMID- 11776093 TI - 99mTc-HL91 "hot spot" imaging of mice bearing human carcinoma by gamma camera and the effects of tumor necrosis on imaging. AB - OBJECTIVE: To evaluate the hypoxia-avid agent 99mTc-HL91 (99mTc labeled 4, 9 diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) as the tracer of tumor "hot spot" imaging and the influence of tumor necrosis on the image. METHODS: After injection of 99mTc-HL91, 6 nude mice bearing human breast cancer MCF-7 and 18 nude mice bearing human pancreatic adenocarcinoma were subjected to gamma camera imaging, postmortem analysis, and autoradiography and imaging of tumor sections. RESULTS: The image of tumor was identified 1 hour after injection of 99mTc-HL91. Images demonstrated gradually increased 99mTc-HL91 uptake in the tumor 1-12 hours after injection (P < 0.05-0.001). Six hours after injection, the radioactivity ratios of tumor to thorax and tumor to head were higher than 2.1. Six hours after injection, the radioactivity ratios of tumor to brain, muscle, blood, heart, lung and kidney in pancreatic adenocarcinoma bearing nude mice were 101.0 +/- 114.7, 30.0 +/- 30.3, 19.9 +/- 21.9, 14.4 +/- 15.1, 3.71 +/- 2.41 and 0.46 +/- 0.26, respectively, and the radioactivity ratios in breast cancer MCF-7 bearing nude mice were close to these figures. The radioactivity of non-necrotic tumor was 3.77 times that of necrotic tumor. However, the radioactivity ratios of tumor to liver, intestine and stomach were lower than 1.3. Autoradiographs and images of tumor sections showed that the radioactivity was higher in the region of solid tumor than in the necrotic region. CONCLUSION: 99mTc-HL91 via gamma camera positively identifies regional tumor in nude mice bearing human cancer. 99mTc-HL91 retention is lower in necrotic tumor than in non-necrotic tumor. The low radioactivity ratio of tumor to abdominal organs limits the application of 99mTc-HL91 in detecting abdominal tumors. PMID- 11776095 TI - The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast: a comparison in sinus rhythm and atrial fibrillation patients. AB - OBJECTIVE: To investigate the relationship between spontaneous echo contrast (SEC) and left atrial appendage (LAA) blood flow velocity using transesophageal echocardiography (TEE) during percutaneous balloon mitral valvotomy (PBMV) in patients with atrial fibrillation and sinus rhythm. METHODS: Thirty-five patients (21 in sinus rhythm and 14 in atrial fibrillation) with rheumatic mitral stenosis underwent PBMV with intraoperative transesophageal echocardiography monitoring. We measured LAA blood flow velocities and observed the left atrium for various grades of SEC (from 0 = none to 4 = severe), before and after each balloon inflation. RESULTS: Left atrial appendage maximal emptying velocity (LAA MEV) was reduced from 35 +/- 14 cm/s to 6 +/- 2 cm/s at peak balloon inflation and increased to 40 +/- 16 cm/s after balloon deflation. Comparison of the values before balloon inflation and after balloon deflation showed that LAA velocities were significantly lower (P < 0.001). During balloon inflation, both maximal emptying velocity (MEV) and maximal filling velocity (MFV) were significantly decreased, compared to those before inflation and after balloon deflation (P < 0.01). And both MEV and MFV were significantly higher after balloon deflation relative to those before balloon inflation. Patients with atrial fibrillation had significantly lower MEV and MFV before and during balloon inflation and after balloon deflation than patients with sinus rhythm. At peak balloon inflation, new or increased SEC grades were observed during 54 of 61 (88%) inflations and unchanged during 7 (12%) inflations. SEC grades were reduced after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%) and remained unchanged after 6 deflations (10%). At peak balloon inflation, left atrium spontaneous echo contrast (LASEC) grade 4 was observed during 14 of 27 (93%) inflations in the atrial fibrillation patients, significantly higher than in patients with sinus rhythm (8 of 34, 24%; P < 0.05). LASEC completely disappeared after 16 of 34 deflations (47%) in the patients with sinus rhythm, significantly higher than in the atrial fibrillation patients (2 of 27 deflations; P < 0.01). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) correlated with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Both the time to lowest LAA velocity and the time to highest LASEC were significantly longer in the patients with sinus rhythm than in the atrial fibrillation patients (2.6 +/- 1.1 s vs 1.7 +/- 1.0 s, P < 0.05 and 2.8 +/- 1.4 s vs 1.9 +/- 1.3 s, P < 0.05, respectively). Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) correlated with the mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). Both intervals are significantly shorter in the patients with sinus rhythm than in the atrial fibrillation patients (2.0 +/- 1.6 s vs 3.5 +/- 1.5 s, P < 0.01 and 2.2 +/- 1.7 s vs 3.6 +/- 1.6 s, P < 0.05). CONCLUSION: Reducing the blood flow velocity in the human left atrium by balloon occlusion of the mitral valve may enhance SEC, whereas restoring blood flow after balloon deflation would cause enhanced echogenic blood to disappear or decrease in both groups of patients. Patients with atrial fibrillation demonstrate more severe blood stagnation of the left atrial body and appendage during transient balloon inflation at mitral valve orifice and slower recovery from the stagnation, decreasing to a lesser extent after balloon deflation, when compared to patients with sinus rhythm. PMID- 11776096 TI - Aristolochic acid I-induced apoptosis in LLC-PK1 cells and amelioration of the apoptotic damage by calcium antagonist. AB - OBJECTIVE: To examine the effect of different concentrations of aristolochic acid I (AAI) in inducing apoptosis of cultured porcine renal cell line LLC-PK1 and to investigate the relationship between intracellular free calcium concentration ([Ca++]i) and LLC-PK1 apoptosis induced by AAI and the influence of a calcium antagonist, lacidipine on apoptosis and [Ca++]i. METHODS: LLC-PK1 cells were treated in different groups: a. the normal group without treatment; b. the group with AAl alone (0.01 g.L-1, 0.02 g.L-1, 0.04 g.L-1, 0.08 g.L-1); c. the group with lacidipine alone (10 ng.L-1, 10(2) ng.L-1, 10(3) ng.L-1); d. the group with AAI (0.04 g.L-1) plus lacidipine (10 ng.L-1, 10(2) ng.L-1, 10(3) ng.L-1). Light microscopy, agarose gel electrophoresis, Annexin-V-Flous apoptosis detection kit and flow cytometry using propidium iodide staining to identify or quantify the apoptosis of LLC-PK1 cells. Mean [Ca++]i was measured by laser confocus microscopy using Fluo-3/AM staining. RESULTS: A series of morphologic changes that were characteristic of apoptosis, Annexin-V-Flous staining positive apoptotic cells and "DNA ladder" were identified in AAI (0.02 g.L-1-0.08 g.L-1) treated LLC-PK1 cells. Quantitative analysis of apoptotic cells showed that the percentage of apoptotic cells in AAI (0.02 g.L-1, 0.04 g.L-1 or 0.08 g.L-1) group was significantly higher than that in normal group (5.3%, 48.5%, 78.7% vs 2.6%, P < 0.001). Mean [Ca++]i was significantly higher in cells treated with AAI (0.04 g.L-1) than that in normal cells (58.01 +/- 18.89 vs 22.66 +/- 4.78, P < 0.001). In group treated with AAI plus lacidipine (102 ng.L-1, 103 ng.L-1), mean [Ca++]i was significantly lower than that treated with AAI alone (35.47 +/- 12.85, 28.55 +/- 10.16 vs 58.01 +/- 18.89, P < 0.001). And the percentage of apoptotic cells in group treated with AAI plus lacidipine (10(2) ng.L-1, 10(3) ng.L-1) was also significantly lower than that treated with AAI alone (19.0%, 27.8% vs 34.7%, P < 0.001). CONCLUSIONS: High concentrations of AAI may induce apoptosis of LLC-PK1 cells. The mean [Ca++]i in AAI-treated LLC-PK1 cells was increased significantly, suggesting that the increase of [Ca++]i may be related to apoptosis in LLC-PK1 cells. Lacidipine may decrease the raised mean [Ca++]i levels caused by AAI and the percentage of apoptotic cells, and lacidipine may ameliorate AAI-induced apoptotic damage by inhibiting the increase of [Ca++]i in LLC-PK1 cells. PMID- 11776098 TI - HLA alleles in patients with Guillain-Barre syndrome. AB - OBJECTIVE: To determine whether genetic factors may work in concert with autoimmune factors in the pathogenesis of Guillain-Barre syndrome (GBS). METHODS: We determined the differences in the distribution of HLA alleles between GBS patients and normal controls. HLA-DQA, -DQB and -DRB alleles were typed by the sequence specific primer polymerase chain reaction (PCR-SSP) methods in 47 GBS, 7 patients with Campylobacter jejuni (CJ) enteritis and 50 normal controls. RESULTS: There were no differences in the frequency of HLA-DQA, -DQB and -DRB among GBS group, CJ group, normal controls and GBS subgroups with respect to recent CJ infection, GM1 IgG and GM1 IgM antibodies (P > 0.05). There was an increasing tendency of DQA1 * 0301 (P = 0.056, RR = 2.991) in the subgroup with GM1 IgG antibodies and DQA1 * 0302 (P = 0.087, RR = 3.587) in the subgroup with recent CJ infection. No difference was found among GBS, CJ enteritis patients and normal controls. CONCLUSIONS: The increasing tendency of the two alleles suggests that there may be some relation between genetic factors and immunological factors, but a definite conclusion waits for more cases. PMID- 11776097 TI - A preliminary investigation of Tanakan in the treatment of hypertensive arteriosclerosis and stroke in rats. AB - OBJECTIVE: To observe the changes in hypertensive cerebral arteriosclerosis and the incidence of stroke in rats following treatment with Tanakan, a preparation of Ginkgo Biloba (GB). METHODS: Using two-kidney, two clip renovascular hypertensive rats (RHRs) as animal models--we investigated changes in these hypertensive arteriosclerosis-associated factors: A I, A II, ALD, ET, SOD and cGMP. Blood levels were observed after oral administration of GB, at both early and late stages of hypertension. RESULTS: The degree of arteriosclerosis was more severe in both RHRs control and the later treated group than in the early treated group, with blood levels of A I, A II, ALD and ET in the former two groups significantly elevated. The degree of arteriosclerosis in the early treated group decreased and the blood levels of A I, A II, ALD and ET in this group decreased nearly to normal levels. The blood levels of SOD and cGMP were also elevated in the early treated group. CONCLUSIONS: These results reveal that it is important to treat hypertension as soon as possible, in order to reduce the occurrence of stroke. PMID- 11776099 TI - Oral administration of insulin to female nonobese diabetic mice inhibited diabetes and induced Fas ligand expression on islets of Langerhans. AB - OBJECTIVE: To detect oral administration of recombinant human insulin to nonobese diabetic (NOD) mice for preventing them from diabetes and insulitis and to detect the effects of oral administration of insulin on Fas and Fas ligand expression on islet of Langerhans. METHODS: Sixty-four female NOD mice were divided into two groups. One group (34) was orally administered recombination human insulin 1 mg in 500 microliters PBS and the other (30) 500 microliters PBS only at age of 5 weeks old, twice a week for the first week, then weekly until 30 weeks of age. RESULTS: Oral administration of insulin to female NOD mice can significantly suppress diabetes and insulitis. The insulitis was less severe in the group fed with insulin than that in the control group (score of insulitis: 1.25 +/- 0.45 vs 3.0 +/- 0.76 at 16 weeks of age, P < 0.01). We examined Fas ligand and Fas expression on islets of Langerhans in both groups of NOD mice by using immunohistochemical techniques. We find that Fas only expressed on islets when the mice suffered the diabetes, whereas Fas ligand expressed on islets of the mice fed with insulin at 16 and 20 week of ages. We did not find Fas ligand positive staining on the islet feeding with PBS. CONCLUSION: We speculated that oral insulin may induce Fas ligand expression on the islets and plays a role in protecting the pancreatic beta-cell from autoimmune destruction. These results show that oral insulin affected autoimmune diabetes and insulitis in NOD mice. The immune mechanism of oral tolerance is closely related to the change of Fas ligand and Fas system. PMID- 11776100 TI - Relationship between the renin-angiotensin system genes and diabetic nephropathy in the Chinese. AB - OBJECTIVE: To clarify whether genetic variants of the renin-angiotensin system (RAS) contribute to the development of diabetic nephropathy (DN) in the Chinese. METHODS: Totally 173 Chinese subjects of Han nationality from Shanghai were classified into! control, DN (-) and DN (+) groups. The latter was subdivided according to diabetic duration at the onset of DN and the stage of DN. Genotyping of five polymorphic sites in four key genes of the RAS: the AGT-T174M, AGT-M235T and AGTR1 genotypes were determined by PCR/restriction enzyme digestion. The insertion/deletion (I/D) and [ACAC] n-STR microsatellite polymorphic markers were used for ACE and REN genotyping, respectively. Statistical analysis showed comparisons of gene frequencies between any two groups were made with Fisher's exact test or Chi-square test. Logistic regression analysis was performed to identify predictors of DN. RESULTS: The frequencies of ACE-DD genotype and ACE-D allele were much higher in DN(+) group than in DN (-) group (0.25 vs 0.05, 0.47 vs 0.29, respectively), so were the frequencies of TT genotype and T allele in AGT-M235T (0.73 vs 0.54, 0.85 vs 0.68, respectively). DN (+) DUR < 5 years group had greatly increased frequencies of AGT-M235T allele and ACE-DD genotype in comparison with DN(-) group (0.92 vs 0.68 and 0.28 vs 0.05, respectively). Logistic regression analysis further identified these two genes as contributing factors to DN. Although AGTR1 and AGT-T174M genotyping analysis revealed differences in frequency distribution between DN (+) and DN (-) or control groups, logistic regression analysis failed to implicate them in the development of DN. CONCLUSIONS: Our study revealed RAS genes, ACE and AGT-M235T but not AGT T174M, AGTR1 or REN genotypes, as contributing factors for DN in type 2 diabetes mellitus in Chinese. PMID- 11776101 TI - Gonadotropin-releasing hormone agonists and laparoscopy in the treatment of adenomyosis with infertility. AB - OBJECTIVE: To study the role and value of gonadotropin-releasing hormone agonists (GnRH-a) and laparoscopy for the treatment of adenomyosis with infertility. METHODS: Four cases were seen with adenomyosis and infertility, 3 of these cases also presented local adenomyomata in the posterior uterine wall. GnRH-a Triptorelin (decapeptyl) or Goserelin (Zoladex) therapy was instituted for six months before laparoscopic surgery for coexisting pelvic pathologic infertility factors in one case and after laparoscopic surgery in three cases. RESULTS: All cases remained amenorrheic during GnRH-a therapy. After the GnRH-a therapy, all enlarged uterus (7-10 weeks gestation size) all decreased to normal or near normal size; menstruation returned in 80-90 days and three cases conceived within four menstrual periods after cessation of treatment. In the 4 cases one pregnancy resulted in the birth of a healthy 3150 g male newborn at 38 weeks gestation by cesarean section; one pregnancy was terminated after adenomyomectomy by emergency cesarean section at 30 weeks gestation because of threatened rupture of uterus; one case was then normal at 28 weeks pregnancy; the last case had 2 resumptive menstrual periods and was still being followed up. CONCLUSIONS: GnRH-a is markedly efficient in reducing adenomyotic uterine size, facilitates uterine or endometrial receptivity for embryos and enhances uterine ability to maintain pregnancy. For adenomyomata associated with infertility, GnRH-a instead of surgical removal of lesions, which are deep in the myometrium, may avoid uterine rupture when pregnancy occurs. For infertility, GnRH-a treatment before laparoscopic surgery greatly decreases surgical difficulties and blood loss in certain cases. PMID- 11776102 TI - Effect of preoperative transcatheter arterial chemoembolization on tumor cell activity in hepatocellular carcinoma. AB - OBJECTIVE: To evaluate the role of preoperative transcatheter arterial chemoembolization (TACE) as a palliative approach in hepatocellular carcinoma (HCC). METHODS: From January 1992 to December 1998, 279 patients with HCC underwent curative liver resection. One to five courses of TACE prior to liver resection were performed in 117 patients (TACE group), while the other 162 patients received only liver resection (control group). All 279 specimens of resected tumors were submitted to the following assessments: PCNA and expression of P53 protein. All specimens from the TACE group were examined for downstaging or necrosis of tumors. RESULTS: In the TACE group, gross inspection revealed downstaging or necrosis of tumor in all cases. Total necrosis (100%) of tumor was observed in 11.1% of 117 patients, > 90% but incomplete necrosis in 15.4%, 50% 90% necrosis in 46.2% and < 50% necrosis in 27.3%. Microscopically, extensive and homogenous coagulative necrosis was observed. Viable cancer cells were also present within and outside the tumor capsule in 111 cases. In the remaining 6 cases, the tumor necrosed completely. In control group, necrosis was observed in 8.0% of 162 cases and reduction of tumor size was < 20%. Microscopically, viable HCC cells were noted in all cases. There was no statistical difference in expression of P53 protein between the TACE and control group. High labeling index of PCNA was significantly higher in the TACE group. CONCLUSIONS: TACE has a marked antitumor effect resulting in various degree of tumor necrosis, but only a small proportion of tumors show complete necrosis. Since the residual tumor cells following preoperative TACE may have more aggressive behavior, we conclude that sequential liver resection is the preferred therapy whenever feasible and preoperative TACE should be avoided in resectable HCC. PMID- 11776103 TI - Inhibitory effects of intestinal mucus on bacterial adherence to cultured intestinal epithelial cells after surface burns. AB - OBJECTIVE: To investigate the relationship between intestinal mucus IgA content and mucus barrier function after surface burns. METHODS: Detection of IgA content in mucus was performed by enzyme linked immunosorbent assay (ELISA) at different time points after burns. Bacterial adherence to cultured epithelial cells (IEC-6) in vitro using E. coli was assessed for each group. RESULTS: The intestinal mucus barrier function declined, parallel to a decrease in IgA content after surface burn in mice. In the normal control group, mucus IgA content was 2.32 D lambda, and 2.51, 1.76, 1.49, 1.06 D lambda at 0.5 h, 1 h, 6 h and 24 h after burn, respectively. Bacterial adherence rate was 0.53 in control group, and 0.46, 0.69, 0.58, 0.81 at 0.5 h, 1 h, 6 h, 24 h after burn, respectively. CONCLUSION: The decrease of intestinal mucus IgA contents is one of the reasons why intestinal mucus barrier function declines after burns. PMID- 11776104 TI - Modified sternal elevation for children with pectus excavatum. AB - OBJECTIVE: To describe our experience in the treatment of pectus excavatum (PE) using a modified sternal elevation procedure. METHODS: From Oct. 1986 to Dec. 1997, 171 patients with PE were admitted to the Department of Pediatric Surgery of the First Hospital of West China University of Medical Sciences. All patients were diagnosed through a history and physical examination. Cardiopulmonary function was assessed by M-mode echocardiography and instrument of pulmonary function in 40 patients before and 4.2 years after surgery which was performed between 1989 and 1994. We performed the following three procedures in the sternal elevation: (1) forming the metal strut in a "arch" shape, (2) suturing the perichondrium into a "pipe" shape, and (3) encouraging patients to do chest expansion exercise after operation. All patients were followed up for 1 to 12 years. RESULTS: The normal contour of the costal cage was enlarged in all but one patient. Exercise tolerance was improved, and cardiac function recovered to the same level as in healthy children, while pulmonary function recovered very slowly after surgery. CONCLUSION: The normal appearance of chest wall can be recovered and normal cardiopulmonary function can be restored by the modified sternal elevation procedure in children with PE. PMID- 11776106 TI - Reporter LacZ gene transfer into cultured ocular cells of human eyes in vitro. AB - OBJECTIVE: To investigate whether a reporter LacZ gene could be transferred into cultured ocular cells of human eyes in vitro. METHODS: Fibroblast cells of Tenon's capsule, trabecular meshwork cells, and muscle cells in the ciliary body of human eyes were cultured and the pcDNA3-LacZ gene was transferred into these cells using a cationic liposome delivery system. The cells were subsequently fixed with 4% paraformaldehyde, mixed with X-gal, then observed under a microscope. RESULTS: Blue stain was seen in the cytoplasm of the cultured cells under the microscope, demonstrating the successful transfer of the LacZ gene into these cells. CONCLUSION: Reporter LacZ gene was easily transferred into the cultured ocular cells in vitro. This provides insights into the transfer of the genes into these cells to study the pathogenesis and therapy of glaucoma. PMID- 11776105 TI - Detection of hepatitis B virus polymerase variations resistant to lamivudine therapy. AB - OBJECTIVE: To investigate variations in hepatitis B virus (HBV) polymerase gene in chronic HBV infected patients resistant to lamivudine therapy. METHODS: Specimens were obtained from nine patients with chronic HBV infection, who were resistant to lamivudine therapy. Partial segments of the HBV DNA polymerase gene were amplified by polymerase chain reaction (PCR). Nucleotide sequence was performed using an applied 373 automated sequencer. Titre of HBV DNA was measured by branched-DNA assay (Chiron). RESULTS: Of nine patients with HBV DNA positive after 64 weeks of treatment, five (56%) had variations in the highly conserved YMDD motif in domain C of the HBV polymerase, three of those were substitutions of isoleucine for methionine (M), and two were substitutions of valine(V) for methionine. Additionally, in two patients with variations characterized by substitutions of V for M, one had a simultaneous amino acid change from the first aspartic acid to glycine and this pattern of variation was not reported in other literatures. With respect to virernia, in two subjects with low titre of HBV DNA (< 100 MEq/ml), no variation was found in the YMDD motif, whereas in seven patients with high titre of HBV DBA (> 300 MEq/ml), five (71%) had variations in the YMDD motif. CONCLUSIONS: Lamivudine is a potent anti-viral agent for treatment of chronic HBV infection. Resistance to lamivudine is likely caused by the variations in the YMDD motif of the HBV polymerase gene. PMID- 11776107 TI - Transient retinal ischemia-reperfusion in rats. AB - OBJECTIVE: To investigate the effect of transient ischemia-reperfusion on the retina in rats. METHODS: Retinal ischemia-reperfusion was induced in rats by increasing the intraocular pressure. After 1 or 5 minutes of ischemia, retinal neuronal cell death at different periods of reperfusion was studied using the TdT deoxynucleotide terminal nick-end labeling (TUNEL) method and light microscopy. Retinal IL-1 beta and TNF alpha were quantified by an enzyme-linked immunosorbent assay (ELISA). RESULTS: A few migrating leukocytes were noticed in the retina after transient retinal ischemia-reperfusion. Rare TUNEL-positive (T+) cells were noticed in the outer granular layer or the rod and cone layer, and not in ganglion cell layer in control eyes, but they were significantly increased in the outer granular layer, the inner granular layer, and ganglion cell layer in the eyes treated with 1 or 5 minutes of retinal ischemia-reperfusion (P < 0.05). Retinal IL-1 beta was significantly increased at 6 hours after reperfusion in the eyes treated with 1 or 5 minutes ischemia over the control eyes (P < 0.05), but retinal TNF alpha was not significantly increased (P > 0.05). CONCLUSION: Transient retinal ischemia-reperfusion for only 1 or 5 minutes of ischemia can induce the upregulation of retinal IL-1 beta and apoptosis of retinal neuronal cells. This kind of apoptosis in individual cells, however, was not sufficient to affect the whole retinal function. PMID- 11776108 TI - The cellular and molecular mechanism of laminin-glycopeptides on anti-metastasis. AB - OBJECTIVE: To further study the anti-metastasis mechanism of laminin glycopeptides on carcinoma cell proliferation, apoptosis and the secretion of matrix metalloproteinases. METHODS: Human hepatocellular carcinoma cells in serum free medium were incubated on laminin-coated substrate with or without laminin glycopeptides at a final concentration of 50 micrograms/ml. The total number of surviving cells after incubating for the indicated time was assayed by MTT assay. DNA synthesis of the incubated cells was detected by 3H-TdR incorporation. Cell cycle was analysed by FACS. The mitotic index of Giemsa stained cells was assessed. Cell apoptosis was detected by both FACS and an acridine orange staining method. Matrix metalloproteinase secretion was analysed by gelatin zymography. RESULTS: The total number of surviving cells incubated on laminin in the absence of laminin-glycopeptides was significantly larger than that in the presence of laminin-glycopeptides. Laminin promoted 3H-TdR incorporation of carcinoma cells, decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase. In contrast, laminin-glycopeptides could inhibit the effect of laminin as shown by 3H-TdR incorporation and cell cycle analysis. The percentage of cells in G2 + M phase and the mitotic index among various groups showed no significant difference. Matrix metalloproteinases secretion from cells treated by laminin-glycopeptides was much less compared to that without the treatment by laminin-glycopeptides. CONCLUSION: Laminin may stimulate cell proliferation, while laminin-glycopeptides could significantly inhibit the effect of laminin by inhibiting DNA synthesis and arresting the carcinoma cell cycle from G1 to S phase. These effects may inhibit not only tumor growth of the primary carcinoma, but also the establishment of metastases at ectopic tissues. Laminin-glycopeptides could also inhibit the secretion of matrix metalloproteinases from carcinoma cells and this may contribute to their decreased invasive and metastatic phenotype. This study further revealed the cellular and molecular mechanism of laminin-glycopeptides on anti-metastasis. PMID- 11776109 TI - Interaction of alcohol and the G to a substitution at the promoter region of the apolipoprotein AI gene in determining plasma apolipoprotein AI levels in Yi and Han Chinese. AB - OBJECTIVE: To investigate the influence on plasma lipid levels of alcohol and a common polymorphism in the human apolipoprotein AI gene promoter at a position 75 bp upstream of the transcription start site. METHODS: For this study, 742 healthy Yi and Han subjects all above 15 years old formed the total population which was divided into three groups: the Yi-farmer group, the Yi-emigrant group and the Han resident group. All estimates of plasma lipids and apolipoproteins were performed using an auto-analyzer. Genetic DNA was prepared from the blood clots using the Triton X-100 lysis technique. Amplification of a 432 bp fragment of the apoAI gene promoter was performed using PCR followed by restriction digestion, electrophoresis and identification of the genotypes involved. RESULTS: The samples were divided on the basis of alcohol consumption: non-drinkers, 1-25 g/day, 26-75 g/day and > 75 g/day. Comparing the four alcohol consumption groups, plasma HDLC and apoAI levels were increased as the alcohol consumption increased with no evidence of threshold effects in the Yi-farmers and the Han people groups. A similar association was found in the Yi-emigrant group, but was not statistically significant. The frequencies of the A allele in the three populations were similar, and no significant difference of lipid and apolipoprotein levels was found between subjects with and without the A allele in the three populations. But, in Han and Yi-emigrant samples, the drinkers with the GG genotype had higher plasma HDLC and apoAI levels than non-drinkers with the same genotype, while the drinkers with the A allele had lower plasma HDLC and apoAI levels than drinkers without the A allele. Non-drinkers with the A allele had higher levels of apoAI than non-drinkers with GG genotypes. It was estimated that 18% of the variability of plasma apoAI level could be explained by the G to A polymorphism in non-drinkers of Yi-emigrants (F = 8.94, P < 0.01). CONCLUSIONS: The present data suggest that moderate alcohol consumption and the G to A substitution could lower the risk of coronary heart disease (CHD), but the beneficial effects of one will be negated by the other. PMID- 11776110 TI - The effects of inhalation of nebulized nitroglycerin on dogs with experimental pulmonary hypertension induced by U46619. PMID- 11776111 TI - Highlights of the 3rd Sino-Japanese Conference on Nuclear Medicine. PMID- 11776112 TI - Intravesical immunotoxin as adjuvant therapy to prevent the recurrence of bladder cancer. AB - OBJECTIVE: To assess the intravesical application of immunotoxin as adjuvant therapy to prevent recurrence after tumor resection in bladder cancer patients. METHODS: An anti-human immunotoxin against bladder carcinoma, BDI-1-RT, was prepared and its in vitro targeting cytotoxicity estimated. The immunoreactivity of BDI-1-RT with human bladder cancer tissue of different grades and stages was detected by immunohistochemical analysis. After safety test, intravesical administration of BDI-1-RT was performed in 31 patients while mitomycin C (MMC) was used in 36 patients serving as a control group. The recurrence rates and side effects in both groups were recorded. In addition, the development of human anti mouse antibodies (HAMA) was determined by ELISA, to assess the potential safety of this immunotoxin. RESULTS: In our study, BDI-1-RT had immunoreactivity with 81.6% of bladder transitional cell carcinomas. The immunoreactivity of BDI-1-RT correlated with tumor grade. High-grade carcinoma had stronger staining than low grade (P < 0.05). There was no significant difference between the BDI-1-RT group (10%) and MMC group (19.3%) in recurrence rate (P > 0.05). Side effects, including systemic and local, were more frequent in the MMC group (11 of 36 patients versus 2 of 31, P < 0.05). HAMA was not detected in any of 7 patients. CONCLUSION: Immunotoxin may have considerable potential in the prophylaxis of bladder transition cell carcinoma. PMID- 11776113 TI - Comparison of computer-photoscreening with non-cycloplegic retinoscopy for amblyopiogenic risk factors in children. AB - OBJECTIVE: To determine the sensitivity and specificity of using a computer photoscreener and non-cycloplegic retinoscopy in the detection of amblyopiogenic factors in nine to fifty months old infants and children. METHODS: Three hundred children, nine to fifty months old, were screened with the computer-photoscreener and non-cycloplegic retinoscopy. With a blinded standardized clinical assessment as the standard, an overall comparison of the sensitivity of and specificity results obtained with the two techniques was made. Photoscreen images on the computer monitor screen were reviewed and analyzed immediately by two independent observers for indicators of amblyopiogenic risk factors. Simultaneously, the results were compared to the findings of a full ophthalmologic examination. RESULTS: The computer-photoscreener revealed a sensitivity of 94.6% and specificity of 90.1%, and the non-cycloplegic retinocopy revealed a sensitivity of 85.7% and specificity of 81.0% for the detection of amblyopiogenic risk factors, including hyperopia (+2.75 D or more), myopia (-1.50 D or more), astigmatism (1.75 D or more), anisometropia (2.00 D or more), ocular misalignment (5 degrees or more), and media opacity (1.5 mm or more). CONCLUSIONS: The computer-photoscreener offers an opportunity to identify problems that limit vision, and could provide a feasible and sufficiently reliable screening technique in infants and preschool children to be screened successfully for amblyopiogenic risk factors. PMID- 11776114 TI - Molecular cloning and protein expression of EC1-2 and EC3-4 epitopes of pemphigus vulgaris antigen. AB - OBJECTIVE: To clone and express EC1-2 and EC3-4 epitopes of PVA (pemphigus vulgaris antigen, desmoglein-3) in order to diagnose pemphigus and study the relationship between epitopes of PVA and anti-PVA antibody. METHODS: RNA was extracted from keratinocytes and the cDNA of epitopes EC1-2 and EC3-4 was synthesized by reverse transcription. Amplified genes of EC1-2 and EC3-4 were inserted into the expression plasmid, PGEX-4T-1, and transformed into E. coli BL21 by electric transduction. Recombinant fusion proteins of EC1-2 and EC3-4 epitopes were expressed by IPTG induction. These proteins were separated on SDS PAGE gels and electroblotted to nitrocellulose to detect the anti-PVA antibody. RESULTS: The sequences of cloned EC1-2 and EC3-4 genes were identical to the sequence registered in PC/GENE. Expressed recombinant proteins reacted only to sera from patients with pemphigus vulgaris, not to sera from patients with bullous pemphigoid, systemic lupus erythematosus or normal persons. CONCLUSIONS: These recombinant proteins are very specific in antigenicity. This may provide a new method for the diagnosis of pemphigus vulgaris (PV) or the differential diagnosis of other bullous cutaneous diseases via patient sera. It is also helpful in understanding the relationship between adhesion molecules and the pathogenic mechanism of pemphigus vulgaris. PMID- 11776115 TI - Molecular epidemiologic study of Mycoplasma genitalium infection in high risk populations of sexually transmitted diseases in China. AB - OBJECTIVE: To detect Mycoplasma genitalium (Mg) infection in high risk populations of sexually transmitted diseases (STDs) from several cities in China and to clarify the possible role of Mg in the pathogenesis of non-gonococcal urethritis. METHODS: Polymerase chain reaction (PCR) based on 2 pairs of primers, one for Mg-Pa (adhesion protein) and the other for 16S-rRNA (Mycoplasma genera) was used to detect Mg infection. Urogenital specimens of different high risk populations and urethritis patients, were collected from the Guangdong, Kunming, Shanghai, Nanjing, and Changzhou areas. RESULTS: The positive detection rate of Mg-DNA in high risk populations of STDs was significantly higher than that of the control group (chi 2 = 7.82, P < 0.01). The positive detection rates in Guangdong STD clinics and promiscuous persons from Kunming were higher than those from the Shanghai, Nanjing, and Changzhou areas (chi 2 = 8.54, P < 0.01 and chi 2 = 5.89, P < 0.05). Mg DNA could be detected in those patients without other relevant pathogens. Some patients were simultaneously infected with Mg and other microbes, such as Chlamydia trachomatis and/or Ureaplasma urelyticum. The positive Mg-DNA detection rate in patients with urethritis symptoms was higher than in patients without the symptoms (chi 2 = 11.68, P < 0.01). CONCLUSION: Mg infection exists in high risk populations of STDs in China, and the Mg infection rate is different among different high risk groups. PMID- 11776116 TI - A comparative study of the dose-response and time course of recovery of atracurium and rocuronium. AB - OBJECTIVE: To compare the characteristics of the dose-response relationship and the time course of action between atracurium and rocuronium in adult patients anesthetized with N2O-O2-fentanyl-thiopene. METHODS: Sixty patients, ASA grade I, aged 18-50 years, scheduled for elective plastic surgery were studied. All patients were randomly divided into either the atracurium or rocuronium group. General anesthesia was maintained with 60% nitrous oxide and 40% oxygen, thiopentone, and fentanyl. Neuromuscular function was assessed using an accelograph with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of the first twitch (T1) was used as the study parameter. The dose-response relationship of atracurium and rocuronium was determined by the cumulative dose-response technique. RESULTS: According to the dose-response curves established by a least squares linear regression, the potency ratio of atracurium to rocuronium was 1:1.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After the intravenous administration of equipotent doses of both drugs (1.5 x ED95), the duration of peak effect, clinical duration, and total duration were significantly different between the two drugs, but their recovery indexes were similar. CONCLUSIONS: Atracurium and rocuronium are low-potency nondepolarizing relaxants with intermediate duration. As compared to atracurium, the neuromuscular blocking effect of rocuronium was about 20% less potent and its duration of action was shorter. PMID- 11776117 TI - CT virtual bronchoscopy: imaging method and clinical application. AB - OBJECTIVE: To evaluate the imaging method and clinical application of CT virtual bronchoscopy (CTVB). METHODS: Fifty-two patients with bronchial and pulmonary diseases were studied with CTVB. All patients underwent fiberoptic bronchoscopy and patients with lung cancers were confirmed pathologically. Lung cancer of center type was found in 46 patients, postoperative lung cancer in 4, tracheal adenoidcystic carcinoma in 1, and bronchial diverticulum in 1. CTVB was performed using Navigator Smooth software on the workstation (Advantage Windows 3.1, GE Medical Systems). Source images included slice thickness of 3 mm or 5 mm, pitch of 1.0 or 1.5, 1.0 mm or 2.0 mm interval (overlap more than 60%) reconstruction. RESULTS: CTVB could reveal vividly the tracheobronchial lumens, the cartilage rings, the carina and the left and right main bronchi, down to the fourth order of bronchial orifices, mimicing fiberoptic bronchoscopy. Among 46 patients with lung cancers of center type, fiberoptic bronchoscopy showed the masses in 45 patients and CTVB displayed the masses in 42. The sensitivity of CTVB was 93.3% and its accuracy was 93.5% (chi 2 = 1.33, 0.10 < P < 0.25). The tumors appeared as masses or nodules, causing bronchial stenosis (n = 35) or occlusion (n = 7). The bronchial rings near the masses were blurred, smooth or absent in contrast to the findings of fiberoptic endoscopy. Postoperative bronchial stump (n = 4) appeared to be smooth. Bronchial diverticulum exhibited a local concavity on CTVB and local protrusion on surface shadow display (SSD). CTVB could pass through the stenotic bronchi and detect the occlusive bronchi from the distal end. CONCLUSIONS: The sensitivity of CTVB in detecting bronchial masses was higher than that of fiberoptic bronchoscopy. Combined with multiplanar reconstruction (MPR) and CTVB can demonstrate the extraluminal extension of tumors. As a noninvasive examining method, however, CTVB is limited to observe mucosal abnormalities and to obtain histologic samples. PMID- 11776118 TI - A randomized controlled clinical trial on etimicin, a new aminoglycoside antibiotic, versus netilmicin in the treatment of bacterial infections. AB - OBJECTIVE: To compare the efficacy and safety of two aminoglycoside antibiotics, etimicin and netilmicin, in the treatment of bacterial infections. METHODS: A randomized, open label, controlled clinical trial was conducted for the treatment of 65 patients hospitalized with respiratory tract infections, urinary tract infections, and skin and tissue infections. Thirty-four patients received etimicin and thirty-one patients received netilmicin at a dose of 100 mg every 12 hours by intravenous infusion. The duration of treatment was 7-10 days in both groups. RESULTS: 47 patients were enrolled in the etimicin group; 35 patients were assessable for safety and 34 patients were assessable for efficacy, 46 patients were enrolled in the netilmicin group; 32 patients were assessable for safety and 31 patients were assessable for efficacy. The results show that overall efficacy was 85.3% for the etimicin group and 83.9% for the netilmicin group, whereas bacterial clearance rates were 87.5% for the etimicin group and 89.7% for the netilmicin group. The incidence of adverse reactions was 8.6% (3/35) and 9.4% (3/32), respectively. CONCLUSION: Etimicin and netilmicin were effective and safe for the treatment of respiratory tract infection, urinary tract infection, and skin and tissue infections. The results show there was no statistically significant difference between the two groups (P > 0.05). PMID- 11776119 TI - Lymphangiogenesis in tumor tissues and 5'-Nase, Flt-4, Flk-1 expressions. AB - OBJECTIVE: To investigate lymphangiogenesis in tumor tissues and 5'-Nase, Flt-4, Flk-1 expressions. METHODS: 5'-Nase and Aplase expressions and the morphology of lymphatics in gastric carcinoma tissues were observed with enzyme histochemistry. Flt-4 and Flk-1 expression in gastric carcinoma and sarcoma tissues was studied by immunohistochemistry. CNE-2z cells were implanted into the subdermal layer of nude mice and hyaluronic acid was injected at the same sites. After 4 or 5 weeks, nasopharyngeal carcinoma (NPC) xenograft tissues were cut for immunohistochemistry and enzyme histochemistry, and lymphangiogenesis, 5'-Nase, Alpase, Flt-4 and Flk-1 expression in NPC tissues was studied. Hyaluronic acid contents in sera of the patients with NPC and mice with NPC xenografts were measured by radioimmunoassay. RESULTS: There were a lot of lymphatics and solid strip-like tissues in gastric carcinoma and NPC xenograft treated with hyaluronic acid. The total number of lymphatics (26.9 +/- 14.2/HP) increased significantly in gastric carcinoma tissues. Flt-4 and Flk-1 positive expression was found in gastric carcinoma, sarcoma tissues and NPC xenograft. Most of the vessels with positive Flt-4 were lymphatics. Flk-1 expression was only found in the walls of blood vessels. Hyaluronic acid content (363.52 +/- 98.15 ng/ml) in sera of patients with NPC was higher than that of the patients with chronic nasopharyngeal inflammation (306.29 +/- 27.15 ng/ml), with a significant difference (P = 0.039). The hyaluronic acid content in sera of nude mice with NPC (2120.59 +/- 490.22 ng/ml) was markedly higher than that in normal mice (1588.99 +/- 502.12 ng/ml), with a significant difference between them (P = 0.007). CONCLUSION: There are a lot of lymph capillaries with positive 5'-Nase in gastric carcinoma and NPC xenograft treated with hyaluronic acid. Flt-4 positive expression is shown in gastric carcinoma, sarcoma tissues and NPC xenografts. The results suggest there is lymphangiogenesis in these malignant tumor tissues. Hyaluronic acid contents in sera of patients with NPC and nude mice with NPC increase, which may promote the formation of lymphatics. PMID- 11776120 TI - Clinicopathologic analysis of angiomyofibroblastoma of the female genital tract. AB - OBJECTIVE: To study the clinicopathologic features and immunoprofile of angiomyofibroblastoma (AMF) with emphasis on differential diagnosis. METHODS: Seven vulvar, two vaginal and one perineal angiomyofibroblastomas were evaluated by light microscopy and immunohistochemistry. The immunohistochemical studies were performed on paraffin-embedded sections using the standard ABC method with a panel of antibodies. RESULTS: Angiomyofibroblastoma predominantly occurred in middle-aged women in the genital region, especially in the superficial area of the vulva. Clinically, most of the tumors presented as slowly growing painless masses and were often diagnosed as Bartholin's gland cysts. Histologically, the tumors were all well-circumscribed and characterized by alternating hypocellular and hypercellular areas with abundant thin-walled blood vessels. The tumor cells were bland and spindle-shaped or epithelioid and tended to concentrate around the vessels or cluster in small nests. Immunohistochemically, the tumor cells expressed vimentin and estrogen receptor protein in all 10 cases and desmin in 9 cases. Three cases showed weak or focal immunoreactivity to alpha-smooth muscle actin and muscle specific actin. All ten patients were treated by local excision. Follow-up showed a benign course with no signs of recurrence. CONCLUSIONS: Angiomyofibroblastoma is a distinctive neoplasm that has a propensity to occur in the female genital tract. Recognition of this entity is important to avoid misdiagnosis with other vulvar angiomyxoid neoplasms. PMID- 11776121 TI - Selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice. AB - OBJECTIVE: To determine whether cholinergic neurons in the basal nucleus magnocellularis (NBM) and the medial septum are affected in transgenic mice overexpressing human amyloid precursor protein 770 (APP770). METHODS: Eight age groups, from 3 months old to 10 months old, of either heterozygous transgenic or non-transgenic mice were used for choline acetyltransferase (ChAT) staining using immunohistochemistry. The number of ChAT-positive neurons was counted on the MCID Image Analysis System. Neurons in the cerebral cortex and area CA1 of hippocampus were also stained with cresyl violet and counted using optical dissector technique. RESULTS: There is no change in the number of forebrain cholinergic neurons in the transgenic mice up to 9 months of age. A loss of these cholinergic neurons starts in 9 months old transgenic mice, with a further decrease in the number of NBM and medial septum neurons in 10-month-old transgenic mice. On the other hand, the number of neurons in the cerebral cortex and hippocampal area CA1 remained unchanged. CONCLUSION: These results demonstrate a selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice. PMID- 11776122 TI - Cerebral venous sinus thrombosis: a clinical study of 23 cases. AB - OBJECTIVE: To describe the etiologies, clinical features and diagnosis of cerebral venous sinus thrombosis. METHODS: We reviewed the records of 23 patients admitted with a documented diagnosis of cerebral venous sinus thrombosis from 1991 through 1999 in the Beijing Tiantan Hospital. RESULTS: Infection was the major condition associated with cerebral venous sinus thrombosis. Pseudotumor cerebri syndrome was the most common manifestation, while hemiplegia, seizure and unconsciousness may occur alone or in association. The diagnostic sensitivity of computed tomography (CT), magnetic resonance imaging (MRI) and digital subtract angiography (DSA) were 59%, 86% and 100%, respectively. The sensitivity of MRI with magnetic resonance angiography (MRA) reached 96%. CONCLUSION: As the clinical findings were found to be nonspecific, CT combined with DSA, or MRI with MRA turns out to be valuable for the early diagnosis of cerebral venous sinus thrombosis. PMID- 11776123 TI - Expression of CDKI p27Kip1 in trophoblastic neoplasm. AB - OBJECTIVE: To evaluate the role of p27Kip1 in tumorigenesis and the development of trophoblastic cell disease. METHODS: Using immunohistochemistry, the expression of p27-protein was investigated in 10 normal chorionic villi in the first trimester of pregnancy, 15 complete hydatidiform moles (HM), 7 invasive moles (IM) and 7 choriocarcinomas (CC). RESULTS: In all cases, immunohistochemical staining localized p27-protein in the plasma. Decreased expression of p27Kip1 was observed in malignant trophoblastic neoplasms with a positive rate of 21.43%, which is significantly less than that in normal chorionic villi (80%) and in complete HM (73.33%) (P < 0.05). The positive rate of p27Kip1 in those complete HM with large uterine size for gestational age was lower than that in those with normal or small uterus (42.86% vs 100%, P < 0.05). CONCLUSION: p27Kip1 may be involved in the tumorigenesis of gestational trophoblastic neoplasm as a negative regulator of the cell cycle. The expression level of p27Kip1 in trophoblastic cells may be a prognostic factor for complete HM. PMID- 11776124 TI - Disseminated Penicilliosis marneffei in a patient with acquired immunodeficiency syndrome: a first case report from China. PMID- 11776125 TI - Alcoholic ketoacidosis in two Chinese patients. PMID- 11776126 TI - Arecagenic oesophagitis: case report with imaging findings. PMID- 11776127 TI - Arg485Lys polymorphism of factor V increases the risk of coronary artery disease in a Chinese population. AB - OBJECTIVE: To explore the relationship between genetic variation in coagulation factor V and the occurrence of coronary arterial disease (CAD). METHODS: Unrelated 86 patients with CAD and 102 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) to detect variations in the entire twenty-five exons of the factor V gene. RESULTS: Polymorphisms in exon 4 [642 G-->T (Ser156)], exon 10 [1628 G-->A (Arg485Lys)], exon 13 [4070 A-->G (His1299Arg)] and exon 16 [5380 G-->A (Val1736Met)] were documented. The study also identified a novel polymorphism in exon 2 (327 A-->G) which did not result in amino acid residue substitution. The Leiden mutation (Arg506Gln) was not detected in any of our 188 subjects. Among the 5 polymorphisms, the allele frequency of 1628 G-->A was significantly different between CAD patients and controls (0.69 vs 0.81, chi 2 = 6.908, P < 0.01). This is the first report of this finding in a Chinese population. CONCLUSION: 1628 G- >A polymorphism is associated with CAD and it may be a risk factor for CAD morbidity in the Chinese population. PMID- 11776128 TI - Transcatheter closure of secundum atrial septal defects using Amplatzer device. AB - OBJECTIVE: To evaluate the feasibility and short term results of transcatheter closure of secundum atrial septal defects (TCSASDs) using Amplatzer occluder device. A new self-centering device, the Amplatzer atrial septal occluder, has recently been evaluated in an animal model with excellent results. This paper reports our clinical research with this device. METHODS: 30 patients underwent an attempt at TCSASDs at an average age of 35.6 +/- 15.9 y (range, 5-62 y) and average weight of 63.6 +/- 14.5 kg (range, 17-78 kg) using the Amplatzer atrial septal occluder. The average ASD diameter measured by transesophageal echocardiography (TEE) was 23.6 +/- 4.0 mm (range, 16-31 mm), and the average atrial septal defects (ASD) balloon stretched diameter was 25.2 +/- 5.8 mm (range, 9-34 mm). All patients had right atrial and ventricular volume overload with a Qp/Qs of 3.4 +/- 1.2 (1.4-5.2). A F8-12 catheter was used for delivery of the device in all patients. RESULTS: The device was placed correctly in all patients. There was immediate and complete closure in 30 patients. The average device waist size used to close the defect was 25.6 +/- 5.9 mm (range, 9-34 mm). There was no episode of device embolization or any other complication. Follow-up was performed using transthoracic echocardiography (TTE) 1 day, 1 month, 3 months, 6 months and 1 year after the procedure. The first day after operation; there was complete closure of the ASD in all patients; there have been no episodes of endocarditis, thromboembolism, or wire fracture. CONCLUSION: TCSASDs using the Amplatzer occluder device was an efficient nonsurgical method which had a very high technical success rate and satisfactory short term and follow-up results. PMID- 11776129 TI - Mechanism of inhibition on activator protein-1 activity by all-trans retinoic acid in gastric cancer cells. AB - OBJECTIVE: To determine the mechanism of all-trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells. METHODS: Gastric cancer cell lines: MGC80-3, BGC-823, SGC-7901 and MKN-45. CAT assay, Northern blot, Western blot, gene transfection and MTT assay. RESULTS: ATRA can inhibit the activator protein 1 (AP-1) activity in ATRA-sensitive cell lines, but not in ATRA-resistant cell line, and the anti-AP-1 activity of ATRA is mediated by its receptor, retinoic acid receptor alpha (RAR alpha). ATRA can also inhibit the expression of cJun and cFos. One of the mechanisms for ATRA to inhibit the growth of gastric cancer cells may be through its inhibitory effect on the AP-1 activity and its influence on up-regulation of RAR alpha expression. The inhibition of cJun and cFos expressions by ATRA may also contribute to the anti-AP-1 activity. CONCLUSIONS: ATRA inhibits the growth of gastric cancer cells through the regulation of AP-1 activity. This action is mediated by RAR alpha. PMID- 11776130 TI - Upregulation of drug sensitivity of multidrug-resistant SGC7901/VCR human gastric cancer cells by bax gene transduction. AB - OBJECTIVE: To investigate the role of bax in a vincristine (VCR)-induced multidrug-resistant (MDR) human gastric cancer cell line, SGC7901/VCR, in which the Bax protein expression level was significantly lower compared with that in parent cells. METHODS: A bax eukaryotic expression vector was constructed and transfected into SGC7901/VCR cells by lipofectamine, and resistant clones were selected by G418. Western blotting detected Bax expression in transfectants. Tetrazolium blue (MTT) assay evaluated the differences in drug sensitivity and cell cycle changes of transfectants were analyzed using flowcytometry (FCM). RESULTS: The bax eukaryotic expression vector was constructed and transfected into SGC7901/VCR cells. Through G418 selection, resistant clones were obtained. Western blotting demonstrated that the expression of Bax protein was markedly increased in bax transduced cells. These cells were more sensitive to adriamycin (ADR) and VCR than mock vector transducted cells. Moreover, bax transfection enhanced ADR-induced apoptosis and VCR-induced G2/M phase arrest of SGC7901/VCR cells. CONCLUSION: Bax was involved in the MDR of SGC7901/VCR cells. PMID- 11776131 TI - Antigenic variation and cytoadherence of PfEMP1 of Plasmodium falciparum-infected erythrocyte from malaria patients. AB - OBJECTIVE: To approve a theoretical basis for the molecular pathogenesis of human cerebral malaria and treatment with prevention. METHODS: The blood samples were collected from 24 patients with cerebral malaria, 143 with falciparum malaria, 34 with vivax malaria and 20 healthy controls from the endemic areas of Yunnan Province, China. Using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) technique, we determined the molecular mass (Mr) of these Plasmodium falciparum (P. falciparum) erythrocyte membrane protein 1 (PfEMP1) molecules. RESULTS: Our findings indicate that higher molecular mass (260 kDa-320 kDa) forms of PfEMP1 were expressed on parasitized erythrocyte (PE) from human cerebral malaria patients. Compared with PfEMP1 expressed on PE from human cerebral malaria patients, the expression of PfEMP1 and Plasmodium vivax (P. vivax) erythrocyte membrane protein 1 (PvEMP1) on PE from falciparum malaria patients and vivax malaria patients did not have multiple bands of PfEMP1 of > or = 260 kDa, but had a PfEMP1 with molecular mass of 240 kDa and a PvEMP1 with molecular mass of 180 kDa band separately. Healthy controls expressed an EMP of molecular mass of 140 kDa. CONCLUSION: Results confirm the antigenic variation of higher molecular mass of PfEMP1 whose molecular mass is equal to or exceeds 260 kDa-320 kDa on PE of patients with cerebral malaria. Our results show that the binding of large antigenic variability PfEMP1 molecular mass of 260 kDa-320 kDa on PE from human cerebral malaria patients with diverse receptor molecules on the endothelial cell (EC) of the cerebral microvessels may be involved in the molecular pathogenesis of cerebral malaria. PMID- 11776132 TI - Telomerase activity and expression of the telomerase catalytic subunit gene in non-small cell lung cancer: correlation with decreased apoptosis and clinical prognosis. AB - OBJECTIVE: To investigate the level of telomerase activation (TA) and telomerase catalytic subunit (hEST2) gene mRNA in patients with non-small cell lung cancer, and determine whether they are associated with tumor cell apoptosis, stage, and clinical outcome. METHODS: Primary tumor specimens from 58 patients untreated with chemotherapy and 10 cases of histologically benign and adjacent lung tissue were analyzed. TA and hEST2 were measured by means of a modified telomerase repeat amplification protocol (TRAP) assay and in situ hybridization (ISH), respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP nick end-labeling (TUNEL) was used to evaluate apoptotic cells. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect bcl-2 mRNA expression. RESULTS: TA and hEST2 were detected in 45 (77.6%) and 43 (74.1%) of 58 tumor specimens, respectively, and not detected in specimens of adjacent and benign lung tissue. One case expressed hEST2 as a weak positive. Statistically significant positive association was found between the level of TA and hEST2 (r = 0.85, P = 0.001). TA and hEST2 were associated with tumor stage, but not associated with tumor grade, gender and patient age. Positive rate of bcl-2 mRNA was 38 (65.5%) of 58 tumor specimens. The mean apoptotic index in the bcl-2 positive group (9.5 +/- 1.3) was lower than that in the bcl-2 negative one (19.8 +/- 2.1, P < 0.05), suggesting that apoptotic index may be inversely associated with bcl-2 expression (r = -0.48, P = 0.041). Bcl-2 expression in the TA and hEST2 positive group (92.1% and 89.4%) was higher than that in the negative one (50.0% and 45.0%, P = 0.043 and P = 0.032, respectively). The apoptotic index was lower in the TA or hEST2 positive group (8.2 +/- 1.4, 10.7 +/- 1.1) than in the negative one (20.5 +/- 1.6, 24.2 +/- 2.1, P < 0.05). A statistically significant inverse association was found between TA or hEST2 and apoptotic index (r = -0.45, P = 0.02 and r = -0.51, P = 0.001, respectively). Positive correlation was also detected between TA or hEST2 and bcl-2 expression (r = 0.86, P = 0.01 and r = 0.73, P = 0.024, respectively). The level of hEST2 mRNA and apoptotic index were associated with clinical outcome in a multivariate cox regression analysis. CONCLUSIONS: High TA and hEST2 were frequently detected in primary non-small cell lung cancer untreated with chemotherapy, having high bcl-2 expression and a low tumor cell apoptotic rate. This suggests that both TA and hEST2 are correlated with the deregulation of apoptosis. hEST2 and apoptotic index have prognostic significance in patients with non-small cell lung cancer. PMID- 11776133 TI - Ultraviolet blood irradiation and oxygenation affects free radicals and antioxidase after rabbit spinal cord injury. AB - OBJECTIVE: To investigate the effects of ultraviolet blood irradiation and oxygenation (UBIO) on free radicals and antioxidase after spinal cord injury in rabbits. METHODS: Totally, 186 rabbits were used and divided randomly into four experimental groups: control (n = 6), blood transfusion (n = 24), injured (n = 96) and treatment (n = 60) groups. The relative intensity of free radical (FR) signals, malondialdehyde (MDA) content, as well as the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were compared among the four groups at 6, 24, 48, and 72 hours and 6 days after injury. RESULTS: The relative intensity of FR signals in spinal cord tissue in the injured group increased at 48 hours and showed a striking difference compared with the control group; in the treatment group, it decreased and showed a striking difference compared with the injured group. MDA content in blood in the injured group increased and showed a striking difference at 6, 24 and 48 hours and showed a significant difference at 72 hours and 6 days after injury compared with the control group. In the treatment group, MDA content in blood decreased and showed a significant difference at 48 hours compared with the injured group. MDA content in spinal cord tissue increased in the injured group and showed a striking difference compared with the control group; in the treatment group, it decreased and showed a striking difference compared with the injured group at the corresponding times. The activity of SOD in blood and spinal cord tissue decreased in the injured group and showed a striking difference compared with the control group; in the treatment group, it increased and showed a striking difference compared with the injured group at the corresponding times. The changes in activity of GSH-PX in blood and spinal cord tissue were similar to that in SOD. No significant difference was observed between the blood transfusion and control groups. CONCLUSION: UBIO can ease free radical damages and elevate the activity of antioxidases after spinal cord injury in rabbits. PMID- 11776134 TI - Angiostatin K(1-3) gene for treatment of human gliomas: an experimental study. AB - OBJECTIVE: To discuss the feasibility of gene therapy of human glioma by antiangiogenesis method. METHODS: Angiostatin K(1-3) cDNA with secretive signal was inserted into the polylinker sites of eukaryotic expression vector pcDNA3 to construct pcDNA-SAK(1-3). The vector was transfected into human SHG44 glioma cells by lipofectamine and the positive clone was screened by G418. The biological characteristics of glioma cells were examined by electronmicroscope and flow cytometry. The activity of angiostatin K(1-3) protein expressed by SHG44 cells was examined by the bovine micrangium endotheliocyte inhibition assay and immunofluorescence assay. When SHG44 cells were implanted into the strata subcutaneum of nude mice, tumor necrosis and micrangium were calculated immunohistochemically and electronmicroscopically for determining their characteristics and validity in gene therapy of human glioma by antiangiogenesis method. RESULTS: The eukaryotic expression vector pcDNA-SAK (1-3) was successfully constructed and transfected into glioma cells. The cells expressed angiostatin K(1-3) protein, and their tumorigenesis and angiogenesis in nude mice were greatly reduced. CONCLUSION: Angiostatin K(1-3) gene is feasible to treat human glioma. This experiment lays a foundation for gene therapy of the other solid tumors by antiangiogenesis method. PMID- 11776136 TI - Clinical significance of changes in beta-adrenoreceptors in peripheral lymphocytes in patients with essential hypertension. AB - OBJECTIVE: To explore the relationship of beta-adrenoreceptor density and function with the condition of patients with essential hypertension. METHODS: In the present study, 69 male patients with essential hypertension at different stages were compared with a group of age-matched normotensive controls. beta adrenoreceptor maximum bound volume (Bmax) in peripheral lymphocytes was measured by 3H-dihydroalprenolol (3 H-DHA) radio ligand binding. beta-adrenoreceptor responsiveness was determined by Salbutamol (injection). RESULTS: In patients with essential hypertension at stages I and II, Bmax was significantly higher (P < 0.01 and P < 0.001, respectively) and the chronotropic doses of Salbutamol required to increase the heart rate by 30 beats/min (CD30) were significantly lower (P < 0.01 and P < 0.001, respectively) than in age-matched normotensive control subjects. In patients with essential hypertension at stage III, Bmax was significantly lower and CD30 was significantly higher (both P < 0.01) than those in the age-matched normotensive control subjects. Bmax was significantly higher and CD30 was significantly lower (both P < 0.001) in patients with essential hypertension and with left ventricular hypertrophy (LVH) than that in patients with essential hypertension but without LVH. In patients with essential hypertension and heart failure, Bmax was significantly lower and CD30 was significantly higher (both P < 0.001) than those in patients with essential hypertension without heart failure. CONCLUSIONS: The changes of beta adrenoreceptor density and function were related to hypertension, hypertension complicated with ventricular hypertrophy, and heart failure. They may be viewed as indexes of the condition in the patients with essential hypertension. PMID- 11776135 TI - Association of coagulation factor VII with the risk of myocardial infarction in the Chinese. AB - OBJECTIVE: To elucidate the association of plasma factor VII coagulant activity (FVIIc) with the risk of myocardial infarction (MI) and to assess the influence of factor VII gene MspI polymorphism and lipid metabolism on FVIIc in the Chinese. METHODS: A total of 137 patients with angiographically confirmed MI and 125 healthy individuals were evaluated retrospectively. Plasma FVIIc was measured by one-stage prothrombin time, and FVII genotype was determined after MspI digestion of polymerase chain reaction-amplified genomic DNA. Serum lipid levels were assessed by routine methods. RESULTS: MI patients had significantly higher levels of FVIIc (119.5% +/- 22.7% vs 99.9% +/- 21.8%, P < 0.01) and total serum cholesterol (5.80 +/- 1.06 mmol/L vs 5.53 +/- 1.08 mmol/L, P < 0.05) than controls, but only FVIIc independently correlated with the risk of MI (OR = 1.04, P < 0.01). There were no significant differences in FVII genotype or allele frequency between patients and controls (P > 0.05). Subjects with the Gln353 allele were associated with significantly lower FVIIc levels than Arg353 homozygotes (99.7% +/- 19.3% vs 111.4% +/- 24.6%, P < 0.05). Serum triglyceride was positively correlated with plasma FVIIc in both control (r = 0.25, P < 0.01) and case (r = 0.87, P < 0.01) groups, but this correlation was restricted to Arg/Arg genotype (r = 0.68, P < 0.01). A significant correlation of total serum cholesterol with FVIIc only appeared in Arg/Arg homozygotes (r = 0.17, P < 0.01). CONCLUSIONS: Our findings support the role of plasma FVIIc as a risk factor for MI in Chinese. Plasma triglyceride and FVII gene MspI polymorphism are two independent determinants of FVIIc. Assay of this polymorphism will be helpful in determining who will benefit most from lipid-lowing therapy. PMID- 11776137 TI - Effect of advanced glycosylation end products on activity of protein kinase C in human peripheral blood mononuclear cells. AB - OBJECTIVES: To investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinase C (PKC) in human peripheral blood mononuclear cells (PBMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs. METHODS: After PBMC were isolated from human peripheral blood and incubated with different concentrations of AGEs-BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32P from [gamma-32 P] ATP into a special substrate using Promega PKC assay kit. RESULTS: AGEs-BSA increased the total PKC activity in PBMC from 83.43 +/- 6.57 pmol/min/mg protein to 116.8 +/- 13.82 pmol/min/mg protein with a peak at 15 min. AGEs-BSA also increased the total PKC activity in a concentration-dependent manner from 83.1 +/- 6.4 pmol/min/mg protein (control) to 119.1 +/- 13.3 pmol/min/mg protein (control vs AGEs-BSA 400 mg/L, P < 0.01). Furthermore, AGEs BSA induced an elevation of PKC activity in a glycosylating time-related manner, from 80.9 +/- 8.2 (control) to 118.3 +/- 11.5 pmol/min/mg protein (glycosylation for 12 wk, P < 0.01). The total PKC activity stimulated by AGEs-BSA pretreated with AG (100, 200 mg/L) was markedly lower than that of AGEs-BSA group not pretreated with AG (P < 0.05, P < 0.01). CONCLUSIONS: AGEs-BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner. The ability of AGEs-BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs-BSA with AG. PMID- 11776138 TI - Relationship between the burden of Pneumocystis carinii, the inflammatory reaction and lung injury in Pneumocystis carinii pneumonia. AB - OBJECTIVE: To study the relationship between the burden of Pneumocystis carinii (P. carinii) and the inflammatory reaction and biochemical markers in bronchoalveolar lavage fluids (BALF) in a rat model of P. carinii pneumonia (PCP). METHODS: Clean grade 50 male Sprague-Dawley rats were immunosuppressed by a subcutaneous injection of 25 mg cortisone acetate twice a week for 8-12 weeks; the PCP model was successfully induced in 14 rats. The inflammatory reaction and biochemical markers of the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and type IV collagenase (matrix metalloproteinases, MMP-2, MMP 9) as well as the values of total protein (TP) and albumin (ALB) in BALF between the mild burden group of P. carinii (involved alveoli < 25% per 100 alveoli, Group A) and the moderate to severe burden group (involved alveoli > or = 25% per 100 alveoli, Group B) were measured. The other six clean grade SD rats served as normal control group (Group C). RESULTS: The total white cell count in BALF was higher in Group B [(6.8 +/- 1.7) x 10(6)/L] than in Group A [(3.8 +/- 1.2) x 10(6)/L] (P < 0.01); however, there were no differences in white cell differentiation. Assays of biochemical markers showed that ALB in BALF in Group B (0.893 +/- 0.469 g/L) was increased in comparison with Group A (0.262 +/- 0.169 g/L); it was only 0.026 +/- 0.021 g/L in Group C. The contents of TP and activities of LDH were higher in Group B (TP 1.756 +/- 0.706 g/L, LDH 2580 +/- 550 U/L) than in Group A (TP 0.784 +/- 0.553 g/L, LDH 1410 +/- 620 U/L); the values of TP and LDH were 0.063 +/- 0.020 g/L and 370 +/- 250 U/L respectively in Group C. The activity of Type IV collagenase, including MMP-2 and MMP-9, was higher in Group B than in Group A (P < 0.01) (MMP-2: 1102 +/- 169 grey value vs 459 +/- 274 grey value; MMP-9: 1218 +/- 257 grey value vs 449 +/- 225 grey value). There was no activity of Type IV collagenase in BALF of Group C. No statistically significant difference was observed in ALP between the groups B and A. CONCLUSIONS: These results indicate that there is a significant correlation between the burden of P. carinii in lung tissues and the inflammatory reaction as well as biochemical markers of the resultant activity of lung injury. PMID- 11776139 TI - Sequence variations of the hypervariable region of hepatitis C virus and their clinical significance. AB - OBJECTIVE: To understand the clinical significance of sequence variations in the hypervariable region (HVR) of hepatitis C virus during infection. METHODS: Eight patients with acute hepatitis C and 20 patients with chronic hepatitis C were followed up for two years. Blood samples were taken at intervals of six months for analysis of HCV-HVR sequences by reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing methods. RESULTS: HCV-HVR sequences of the 28 patients changed in various degrees. 92% of these nucleotide substitutions led to changes of corresponding aminoacid sequences. Only 8% of changed nucleotide were synonymous substitutions. Of 27 amino acids variation of amino acid ranged from 1 to 20 (mean 8, 30%). The most common nucleotide substitution (62%) occurred in the first position of codon, 31% in the second and the rest in the third. HVR variation rate was 0.89 x 10(-1) per genome site per year in acute hepatitis C, compared with 2.31 x 10(-1) per genome site per year in chronic hepatitis C (P < 0.05), but had no relation to HCV subtype. Variation of HVR in the flare up type (ALT > 150 mu/L) was much more than that in the quiescent type (ALT < 100 mu/L). CONCLUSION: Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host immune pressure and might play a major role in the establishment of persistent infection as well as in the flare-up of hepatitis. PMID- 11776140 TI - Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection. AB - OBJECTIVE: To study whether liver cirrhosis associated with Helicobacter pylori (H. pylori) infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. METHODS: Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H. pylori infection and non-cirrhotic patients (splenic rupture) with and without H. pylori infection, and the serum ammonia was measured. RESULTS: The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori infection were 167.82 +/- 8.97 mumol/L (portal vein) and 142.2 +/- 13.35 mumol/L (cubital vein). They were increased significantly as compared with cirrhotic patients without H. pylori infection (47.68 +/- 12.03 mumol/L portal vein and 37.23 +/- 7.04 mumol/L cubital vein), and also compared with the groups of splenic rupture patients with and without H. pylori infection (P < 0.01). There was no significant difference between the serum ammonia level of the cubital vein and portal vein (P > 0.05). CONCLUSIONS: H. pylori infection can induce an increase in serum ammonia in patients with liver dysfunction, and the peripheral serum ammonia measurement may replace the portal vein serum ammonia as a monitoring method. Eradication of H. pylori in cirrhotic patients may prevent hepatic encephalopathy (HE). PMID- 11776141 TI - Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis. AB - OBJECTIVE: To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. METHODS: Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25 patients with type IV lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN). Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients. RESULTS: Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA + cells/TdT + cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r = 0.4983 (P = 0.0132), r = 0.8399 (P < 0.001), r = 0.6614 (P = 0.0033), respectively. P/T ratios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein, r = 0.8554 (P < 0.001) and r = 0.7134 (P = 0.001); and a negative correlation with creatinine clearance (Ccr), r = -0.4880 (P = 0.0133) and r = -0.7229 (P = 0.001), which in tubules positively correlated with serum creatinine (Scr), r = 0.4107 (P = 0.0414). CONCLUSIONS: Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological changes. PMID- 11776142 TI - Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats. AB - OBJECTIVE: To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats. METHODS: Insulin or aminoguanidine was administered to diabetic rats. Blood glucose, hemoglobin A1c (HbA1c), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed. RESULTS: Levels of blood glucose, HbA1c and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased (P values all less than 0.01) in diabetic rats. Insulin could decrease the formation of HbA1c and AGE, and improve PKC activity. Aminoguanidine had no influence on PKC activity (P > 0.05) although it decreased the formation of AGE. Both drugs could delay the increase of urine Pr/Cr ratio and GBMT (P < 0.05 or P < 0.01). CONCLUSIONS: Chronic hyperglycemia may lead to an increase of PKC activity. HbA1c and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening. It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy. PMID- 11776143 TI - Relationship between gene expression of nitric oxide synthase and androgens in rat corpus cavernosum. AB - OBJECTIVE: To clarify the dependence of neural nitric oxide synthase mRNA (nNOSmRNA) and endothelial nitric oxide synthase mRNA (eNOSmRNA) on androgens (testosterone [T] and dihydrotestosterone [DHT]). METHODS: 160 male Sprague Dawley (SD) rats were divided into Groups A (56 rats, 5 weeks old), B (50 rats, 10 weeks old) and C (54 rats, 58 weeks old). Groups A, B and C were all subdivided respectively into five Subgroups. Subgroup 1: intact controls; Subgroup 2: castrated; Subgroup 3: castrated with testosterone undecanoate 25 mg/kg.mon-1, intramuscular injection, Subgroup 4: castrated with testosterone undecanoate 50 mg/kg.mon-1, intramuscular injection and Subgroup 5: treated with finasteride 4.5 mg/kg.day-1, orally. Four and ten weeks after treatments described above, one half of the rats were killed. Serum samples were taken for measurements of T, free testosterone (FT) and DHT by radioimmunoassay. Penile samples were treated with liquid nitrogen and then stored at -80 degrees C. nNOSmRNA and eNOSmRNA were detected by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and Dot blot. RESULTS: There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 in all Groups A, B and C. The expression of penile eNOSmRNA of Group A was significantly increased (4 weeks model) (P < 0.05) or increased (10 weeks model) (P > 0.05) in Subgroup 2 or 5 compared with those in Subgroup 1. There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 of Group B in 4 weeks model (P > 0.05). There was an elevation when animals were castrated or treated with finasteride in the 10 weeks model. The expression of penile eNOSmRNA of Group C was significantly increased (10 weeks model) (P < 0.05) or increased (4 weeks model) in Subgroup 2 compared with those in Subgroup 1. The production of eNOSmRNA in Subgroup 5 was also increased (including 4- and 10-week models). When T was supplied for castration, the penile eNOSmRNA was decreased to some extent; the greater the dose of T given, the lower penile eNOSmRNA was observed. CONCLUSIONS: The expression of eNOSmRNA in SD rat penile tissue increases while T or DHT diminishes. Sometimes androgens modulate penile eNOSmRNA in opposite directions. There is no correlation between the expression of nNOSmRNA and androgens (including T and DHT). Androgens give rise to penile erection probably not via the NOS pathway. PMID- 11776144 TI - Treatment of rats with experimental allergic neuritis using high dose immunoglobulin. AB - OBJECTIVE: To investigate the therapeutic potential of high-dose immunoglobulin (HIG) in experimental allergic neuritis (EAN) to provide a theoretical basis of its clinical use in the treatment of human inflammatory demyelinating neuropathies. METHODS: Female Lewis rats were induced to EAN, and divided into experimental and control groups. The rats were treated with either 0.3 g/kg.day-1 of IgG or an equivalent volume of 0.15 mol/L glycine. Clinical, electrophysiologic, and histologic evaluations were carried out in a blind fashion. RESULTS: Clinically, rats treated with IgG had significantly less severe symptoms (P < 0.001) and slower progression (P < 0.001) than controls. Electrophysiologically, the mean conduction latency of the experimental group was significantly shorter than controls (P < 0.05). Histologically, rats treated with IgG prepared from normal Lewis rats had a significantly lower percentage of demyelinated fibers (P = 0.01) and total abnormal fibers (P < 0.001) than controls. Statistically, clinical, electrophysiologic and morphologic data were all significantly correlated. CONCLUSIONS: The EAN animal model is reliable for observation of HIG effects, and useful to provide data for clinical work. HIG has a significant therapeutic effect in EAN when given soon after disease onset. It can reduce clinical disease severity and decrease the number of demyelinated fibers as well as the number of total abnormal fibers. For the current controversy over whether HIG is effective, the results of this research support the clinical use of HIG in human demyelinating neuropathy. PMID- 11776145 TI - Practice of breast self-examination among high risk Chinese women in Hong Kong. AB - BACKGROUND: The incidence of breast cancer in Hong Kong is increasing and breast self-examination (BSE) as a screening tool is becoming more popular, especially among first-degree relatives (FDR) of breast cancer victims. BSE may be more applicable to Chinese women as their breast size is smaller. This study explores the BSE practice in this group of women. METHODS: A cross sectional study was conducted by sending questionnaires to 330 FDR of breast cancer patients treated in the Department of Surgery, University of Hong Kong. BSE behavior was studied with respect to its frequency, awareness, completeness and confidence of practice. RESULTS: 110 subjects returned the questionnaires with a response rate of 33%. The mean age of the respondent was 37 years. Only 57 women (52%) were practicers. The practicers have a stronger BSE awareness (P < 0.01) and a lower mean score on thought barriers (P = 0.002) than the non-practicers. 40% of the practicers gain their BSE knowledge through clinicians and their mean period of practice was 3.2 years. 68% of the practicers performed BSE completely. The overall confidence rate was 35%, but the rate was 43% among those who performed complete BSE. Thirteen factors possibly related to the completeness and rate of confidence of BSE examination were studied. The only factor that significantly determined completeness was the time spent for each examination (P = 0.002). The complete practicers required a longer time than the incomplete practicers (6.60 and 2.96 min, respectively). Women with a stronger BSE intention (P = 0.001) and a lower mean score on thought barriers (P = 0.001) performed the examination confidently. CONCLUSIONS: Slightly over half of the FDR practice BSE. The majority perform a complete BSE but they are not confident in finding abnormalities. Women spending more time on BSE are associated with a higher rate of completeness. However, only those with a stronger BSE intention and lesser thought barriers are more confident in their practice. PMID- 11776146 TI - Two cases of combined liver-kidney transplantation. AB - OBJECTIVES: To report the clinical experiences of simultaneous hepatorenal transplantation. METHODS: We performed simultaneous hepatorenal transplantation in one patient with liver cirrhosis of hepatitis B and uremia of chronic nephritis on February 1, 1999 and one patient with liver cirrhosis of hepatitis B complicated by hepatorenal syndrome on March 12, 1999. The donors were heart arrest cases. Rapid multiple organ harvesting techniques and UW solution infusion in situ were used. Liver and kidney transplantation were orthotopic and ordinary methods, respectively. Immunosuppressive drugs consisted of cyclosporine, Cellcept, ALG and cortstco steroids. Lamividine was used on day 50 and day 40 postoperation, respectively. RESULTS: Both transplanted organs rapidly achieved normal function postoperation and the patients recovered well but suffered mild kidney rejection day 110 postoperation in No 1 patient. In No 2 patient, acute renal function failure, mental symptoms, muscle spasm, cerebral artery thrombosis, inhalation pneumonia and chronic liver graft rejection ensured sequentially but were controlled. The patients have survived for more than nine and eight months, respectively, with normal life quality. CONCLUSIONS: Combined hepatorenal transplant is a radical treatment method for liver and kidney function failure and requires more comprehensive techniques than isolated single organ transplantation. Preventing the recurrence of hepatitis B by oral lamividine may be a key to long-term survival. PMID- 11776147 TI - Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats. AB - OBJECTIVE: To investigate early changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats. METHODS: Male Sprague-Dawley rats were divided into 4 groups: normal controls (NL, n = 10), intrahepatic portal hypertension (IHPH, n = 10) induced by injection of CCl4, normal rats with OLT (NL-OLT, n = 9) and IHPH rats with OLT (IHPH-OLT, n = 16). IHPH-OLT rats were divided into 2 subgroups: 3 days (Group A, n = 9) and 7 days (Group B, n = 7) after OLT. OLT was performed in rats using cuffs for the anastomosis of the suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Two weeks after production of IHPH rats, 7 days after NL-OLT rats, 3 days and 7 days after IHPH-OLT rats, radioactive microspheres were used in a hemodynamic study. RESULTS: There were no significant differences in hemodynamic changes between NL-OLT and NL rats, except mean arterial blood pressure (MAP). The characteristics of systemic and splanchnic hyperdynamic circulatory state, including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance were observed in IHPH, IHPH-OLT A, and IHPH-OLT B rats. The magnitude of hyperhemodynamics was in the order of IHPH > IHPH-OLT A > IHPH-OLT B rats. Moreover, the derangement of splanchnic hyperhemodynamics was more significant than that of systemic hyperthermodynamics. CONCLUSIONS: The present study demonstrates that the persistence of early systemic and splanchnic hyperkinetic circulation after OLT may be the consequence of factors which maintain hyperhemodynamics in liver cirrhosis, where portal hypertension is not completely eliminated. Hyperhemodynamics is not induced by OLT per se. PMID- 11776148 TI - Expression of the MAGE-1 gene in human hepatocellular carcinomas. AB - OBJECTIVE: To further investigate the expression of MAGE-1 gene in hepatocellular carcinoma (HCC). METHODS: The tumors and adjacent liver tissue from 45 HCC patients and liver tissue from 28 non-HCC patients (16 with liver cirrhosis and 12 with normal liver) were characterized by RT-PCR. A 421 bp PCR product from a cDNA fragment spanning exons 1, 2 and 3 was sequenced. The HLA type was assayed by standard ELISA in 43 HCC patients. RESULTS: Thirty-two of 45 tumor tissues from HCC patients expressed MAGE-1 mRNA (71.1%). In contrast, MAGE-1 mRNA was not detected in adjacent tissues. Three were found to have point mutations at 3 identical sites resulting in the substitution of two amino acid residues. The most frequent HLA types in 43 HCC patients were: HLA-A2, 53.5%; A11, 25.6%; A24, 20.9%; A33, 20.9%; HLA-B13, 28.3% and B35, 23.2%. Expression of HLA-A33 (20.9%) was higher in HCC patients than that predicted in the normal Chinese population (8.8%). There was no discemable correlation between MAGE-1 expression and alpha FP level, tumor size and hepatitis B or C virus infection. The identification of peptides which are restricted by haploptypes other than A1 should increase the opportunity for peptide based immunotherapy. CONCLUSIONS: This study shows that MAGE-1 mRNA is highly expressed in HCC tumor tissue in Chinese patients. Previously unreported point mutations in the MAGE-1 gene are described and may also provide additional opportunities for immunotherapy. PMID- 11776149 TI - Design and clinical application of cervical hollow threaded fixator. AB - OBJECTIVE: Cervical hollow threaded fixator (CHTF) was designed and applied to stabilize the cervical spine following anterior decompression due to cervical spondylosis or acute cervical disc herniation. METHODS: Medical use titanium alloy with no magnetism was made into a hollow threaded structure with holes on the wall of the fixator. Forty-two patients with cervical spondylosis and acute cervical disc herniation were stabilized using the CHTF technique after anterior decompression. X-ray films and CT scans were taken after the operation to observe the stability and fusion rate of the segments. RESULTS: Patients were allowed to walk one day after the operation and were followed up for 6 to 36 months. The operated segments were stable and solid fusion was observed 3-6 months after surgery. CONCLUSIONS: Immediate stability of the operated segments can be obtained using the CHTF technique. Patients were easy to manage after the operation and returned to their jobs in a short time. The CHTF technique is safe and simple to perform and eliminates the complications of an autograft. It may be an alternative to traditional cervical interbody fusion with bone graft. PMID- 11776150 TI - Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL 8, MCP-1, RANTES and their receptors, and their selective migration to these chemokines. AB - OBJECTIVE: To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC-CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte-derived dendritic cells (MoDCs). The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was also studied. METHODS: In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratory ability was assessed by a micromultiwell chemotaxis chamber assay. RESULTS: IL-8, MCP-1, RANTES and their corresponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable after 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. CONCLUSION: Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses. PMID- 11776151 TI - The prevalence of lactase deficiency and lactose intolerance in Chinese children of different ages. AB - OBJECTIVE: To determine lactose metabolism and lactase activity in Chinese children of different ages, prevalence of lactase deficiency (LD), and lactose intolerance (LI). METHODS: All 1168 healthy subjects between 3 and 13 years were recruited from schools in four large cities in China. They were screened by a 25 g lactose tolerance test. Some subjects were challenged with 50 g milk powder on different days. Both indicators, the expiratory H2 concentration and intolerance symptoms, were analyzed. RESULTS: LD occurred in 38.5% of children in the 3-5 year age group, and 87% of the 7-8 year and 11-13 year old groups. The age of occurrence for LD may be at 7-8 years among Chinese children. The prevalence of LI among Chinese children was 12.2% at age 3-5 years, 33.1% at age 7-8 years, and 30.5% at age 11-13 years, respectively. CONCLUSION: The results demonstrate that LD is very common in Chinese children from these four cities. LD and LI have a dose dependent response: lactose absorption and symptoms are based on lactase activity. The relationship between breast feeding history (or the history of cow milk intake) and lactase activity among Chinese children has not been established. PMID- 11776152 TI - In situ RT-PCR detection of inducible nitric oxide synthetase gene expression in lung during endotoxemia in rabbits. AB - OBJECTIVE: To detect the location of inducible nitric oxide synthetase (iNOS) protein and mRNA in lung during endotoxemia in rabbits. METHODS: Northern blotting was performed before, 1 hour and 5 hours after the intravenous administration of lipopolysaccharide (LPS) in rabbits. Immunohistochemical analysis (IA), in situ hybridization and in situ reverse transcription-polymerase chain reaction (in situ RT-PCR) were also performed in lung sections. RESULTS: iNOS mRNA expression was found using Northern blotting in lung 5 hours after LPS injection, while it was not found in control. The positive stain was found only in macrophages in lung 5 hours after LPS injection by standard hybridization and IA; while by in situ RT-PCR, the amplification products were found in macrophages, airway epithelial cells, vascular endothelial cells, smooth muscle cells and leukocytes, in addition to macrophages distributed abundantly throughout the lung. The signal was absent in control or samples. CONCLUSIONS: Using an in situ RT-PCR technique, iNOS expression was not only observed in macrophages but also in many other kinds of cells in lung during endotoxemia in rabbits. This suggests that in situ RT-PCR is much more sensitive than in situ hybridization, and can be used to examine genes with low expression. PMID- 11776153 TI - Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients. AB - OBJECTIVE: To investigate the role of hepatitis C virus (HCV) in the malignant transformation of bile duct cells. Tissues from 6 Chinese patients and 6 American patients with cholangiocarcinoma were studied. METHODS: RNA was extracted from the selected tumor areas of formalin-fixed, paraffin embedded sections, followed by reverse transcription double polymerase chain reaction (RT-PCR) and Southern blotting. RESULTS: Positive and negative strand HCV RNA sequences were detected in seven out of twelve patients with cholangiocarcinoma. A high positive rate was found in Chinese patients (83%) as compared to US patients (33%). CONCLUSION: Our finding suggests HCV may play a role in the malignant transformation of bile duct cells. PMID- 11776154 TI - Successful treatment of invasive burn wound infection with sepsis in patients with major burns. AB - OBJECTIVE: To investigate the clinical characteristics of invasive burn wound infection with sepsis in patients with major burns and to summarize the successful experiences in the treatment of such patients. METHODS: Eight patients with major burns, complicated by invasive burn would infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock. The plasma concentrations of IL-6, IL-8, TNF alpha and lypopolysaccharide (LPS) were assayed before and after surgical intervention, as well as when the patient's vital signs became stable. RESULTS: The patients' conditions usually deteriorated abruptly when extensive invasive burn wound infection emerged. While multi-microbial infection was usually found, Pseudomonas aeruginosa was the predominant bacteria isolated from the subeschar tissue. The plasma concentrations of IL-6, IL-8, TNF alpha and LPS before surgical intervention were significantly higher than those after surgical intervention (P < 0.05). The lowest levels of the inflammatory mediators were observed when the patients' conditions became stable, and the values were significantly lower than those before surgical intervention (P < 0.001). CONCLUSION: Since the main cause of burn wound sepsis is the presence of a large area of infected burn wound, they should be excised and covered as early as possible. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn sepsis. Although favorable results should be attributed to comprehensive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role. PMID- 11776155 TI - Gastric rupture caused by acute gastric distention in non-neonatal children: clinical analysis of 3 cases. AB - OBJECTIVE: To study gastric rupture, a progressive, rapid and high mortality condition, caused by acute gastric distention (GRAGD) and its appropriate diagnosis and treatment. METHODS: The etiology, pathology, clinical manifestations and experiences in 3 children with GRAGD were reviewed. RESULTS: Case 1: After diagnosing GRAGD and stabilizing her shock with massive fluid replacement, gastrostomy was performed. Her postoperative course was uneventful because of fasting, suction, fluid infusion, correction of acidosis and supporting nutrition. Case 2: After diagnosing gastric distention which subsided with conservative therapy for 9 days, she suddenly had gastric rupture when she had not eaten for 6 days. She died of shock and had no chance for surgery. Case 3: The patient had sudden abdominal pain, distention and vomiting with severe shock for 4 days. Emergency surgery found gastric rupture and the method was the same as Case 1. The patient survived but has brain impairment. Case 1 and 3 showed multifocal transmural necrosis. CONCLUSIONS: Symptoms like overeating, bulimia, changes in kind of food, X-ray showing large distended stomach and massive pneumoperitoneum were seen after gastric rupture and can help to diagnose this condition. Clinical course of gastric distention with toxic shock progresses rapidly, however subsequent gastric rupture exacerbates the shock and makes the treatment difficult treatment. It is extremely important that a laparotomy be performed at once after stabilizing shock with massive fluid replacement. Postoperative nutritional support and fluid replacement will increase survival. It is very important that when gastric distention disappears after conservative therapy, the doctor should assess carefully whether the gastric wall recovery is under way by using effective methods of examination. PMID- 11776156 TI - Treatment of spontaneous coronary artery dissection: report of two cases. PMID- 11776157 TI - [Cytoreductive surgery in the management of stage IV epithelial ovarian cancer]. AB - OBJECTIVE: To determine the role of cytoreductive surgery in patients with stage IV epithelial ovarian cancer. METHODS: From Jan. 1986 to Dec. 1997, 71 patients with stage IV epithelial ovarian cancer who were surgically treated in our hospital were retrospectively reviewed. Survival was calculated by Kaplan-Meier method with differences in survival estimated by Log-rank test. Independent prognostic factors were identified by the COX's stepwise regression model. RESULTS: Thirty (42.3%) of 71 patients were successfully debulked (< or = 1 cm) at the time of initial surgery. The estimated 5-year total survival rate was 6.1%. There was a significant difference in survival between patients optimally (13.7%) vs. suboptimally (0.0%) cytoreduced, with an estimated medium survival of 23 months in optimal group vs. 9 months in suboptimal group (P < 0.001). When the variables were factorized, optimal cytoreduction could get the greatest benefit. Only in patients with malignant pleural effusion or positive supraclavicular lymph node. Multivariate analysis revealed that size of residual disease and ascites were independent factors for both overall and progression-free survival (P < 0.05). CONCLUSIONS: Optimal cytoreductive surgery is an important determinant of survival in women with stage IV epithelial ovarian cancer, especially in those with malignant pleural effusion or positive supraclavicular lymph node pathology. PMID- 11776158 TI - [Treatment and prognostic factors for stage IV epithelial ovarian cancer]. AB - OBJECTIVE: The aim of the study was to evaluate the influence of surgical debulking and chemotherapy on survival in patients with stage IV epithelial ovarian cancer. METHODS: Medical records and follow-up sheets were retrospectively reviewed for all women with International Federation of Gynecology and Obstetrics stage IV epithelial ovarian cancer treated between January, 1982 and December, 1997 in our hospital. Survival analysis and comparison were performed using Kaplan-Meier method and t-test. The COX proportional hazards regression model was used to identify independent variables associated with survival improvement. RESULTS: Twenty-five women with stage IV epithelial ovarian cancer were available. Median age was 51 years (range 33-72 years). Papillary serous histology was found in 12/75 patients (48%). Thirteen patients (52%) had grade 3 tumors. Metastases by the International Federation of Gynecology and Obstetrics (FIGO) criteria were found in 7 cases in supraclavicular lymph node (28%), 6 cases in liver (24%) and 4 cases with malignant pleural effusion. All patients received surgical debulking with 9 cases (36%) having in optimal cytoreduction. Overall median survival of 15.0 months was achieved, while optimal debulked patients' median survival was 28.4 months compared to 14.7 months for the patients with bulky residual disease (P < 0.01). Median survival for the patients with 6 or more courses of chemotherapy postoperatively was 28.5 months, compared to 6.5 months for the patients with less than 6 courses (P < 0.01). Optimal debulking surgery and courses of chemotherapy retained significance as indepent predictors of survival based on multivariate analysis. CONCLUSION: Optimal surgical debulking and active postoperative chemotherapy appear to improve the prognosis of the patients with stage IV epithelial ovarian cancer under the premise of keeping quality of life. PMID- 11776159 TI - [Study on the relationship between methylenetetrahydrofolate reductase gene polymorphism and plasma homocysteine level in pregnancy induced hypertension patients]. AB - OBJECTIVE: To investigate the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and plasma homocysteine level in pregnancy induced hypertension (PIH) patients. METHODS: The MTHFR genotypes were determined in 62 PIH patients and 90 normal pregnant women by the restriction fragment length polymorphism method, plasma homocysteine level was measured by high performance liquid chromatography and fluorescence detection. RESULTS: The frequencies of T677 allele (0.52) and the T677/T677 genotype (0.27) in the PIH group were markedly higher than those in the control group (0.31 and 0.13, P < 0.05, P < 0.01 respectively), mean plasma homocysteine level in the PIH group (9.62 +/- 2.11) mumol/L was also significantly higher than that in the control group (6.85 +/- 1.98) mumol/L (P < 0.01). CONCLUSION: The MTHFR gene T677 variant is the genetic high risk factor for PIH. It can induce the hyperhomocysteinemia, potentially contributing to the pathogeny of PIH. PMID- 11776160 TI - [Study on human leucocyte antigen-DQ region gene polymorphism in cases of habitual abortion with anticardiolipin antibody]. AB - OBJECTIVE: To investigate the relationship between human leucocyte antigen(HLA) DQ region gene polymorphism and habitual abortion with anticardiolipin antibody(ACL). METHODS: Polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) was used to type HLA-DQA1 and HLA-DQB1 alleles in 30 cases of habitual abortion with anticardiolipin antibody and 90 women with normal pregnancy history. RESULTS: The frequency of DQB1 * 0303 was found to be significantly higher in ACL(+) habitual abortion group (33.3%) than those in normal control group (P < 0.05). Whereas, there was no significant difference found not only in frequency of other DQB1 alleles, but also in frequency of DQA1 alleles and DQA1-DQB1 haplotypes between two groups. CONCLUSION: The results show an association between ACL(+) habitual abortion and HLA-DQB1 * 0303, which suggest DQB1 * 0303 may be susceptible gene to ACL(+) habitual abortion. PMID- 11776161 TI - [Immunotherapy by B-lymphocytes in patients with unexplained habitual abortion]. AB - OBJECTIVE: To investigate the safety and efficacy of immunotherapy in patients with unexplained habitual abortion(UHA) with increased human leukocyte antigen (HLA) mutual antigen. METHODS: Twenty-four UHA women were immunized by their husband's B-lymphocytes for 3 months. RESULTS: Twenty-two of them had increased HLA mutual antigen. The their anti-paternal lymphocytotoxic antitody (APCA) positive rate was 8% before immunization, significantly lower than that of the control group (86%). After immunization, the APCA positive rate increased significantly to 75%, 20 cases achieved pregnancy and 16 deliverd normal newborns. CONCLUSION: Immunotherapy by husband's B-lymphocytes is effective in UHA with increased HLA mutual antigen, and may have less adverse effect. PMID- 11776162 TI - [Expression of leukemia inhibitory factor in human decidua]. AB - OBJECTIVE: To study the expression and localization of leukemia inhibitory factor (LIF) in human first trimester decidual. METHOD: By immunohistochemical analysis and in situ hybridization, the LIF mRNA and protein expression were observed in 16 cases of human decidua. RESULTS: LIF mRNA and protein expressions were observed in all decidual specimens, the glanduar epithelium showed higher LIF expression than in stromal cells. CONCLUSION: Expression of LIF in human decidua may contribute to embryo implantation, maintenance of placental functions and embryonic growth promation. PMID- 11776163 TI - [Twelve cases of vaginal reconstruction using neurovascular pudendal-thigh flaps]. AB - OBJECTIVE: To summarize the experience in vaginal reconstruction using neurovascular pudendal-thigh flaps. METHODS: The pudendal-thigh flaps lateral to labia majora with the external branches of labial posterior blood vessels in the pedicle were elevated and brought to the midline through tunnels formed under labia majora. The two flaps were then sutured together to create a new vagina. Flap size varied from 9 cm x 4 cm to 14 cm x 5 cm. RESULTS: In twelve cases aged 14 to 44 years including congenital absence of vagina, testicular ferminization syndrome and transsexual patients a new vagina was constructed with neurovascular pudendal-thigh flaps. One patient developed complete necrosis of unilateral flap, followed by formation of rectovaginal fistula. In other patients the flaps all survived and the neovagina was spacious and quite deep. CONCLUSION: The vaginal reconstruction using pudendal-thigh flaps is one of the best methods of vaginoplasty. The technique is simple and reliable. The flap has good blood supply and no stents or dilators are needed after operation. The donor site is hidden with little secondary deformity. The neovagina has a natural angle for intercourse and is sensible. PMID- 11776164 TI - [Evaluation on the compliance of livial therapy in peri and postmenopausal women]. AB - OBJECTIVE: To evaluate the compliance of livial therapy in peri and postmenopausal women. METHODS: One hundred thirty four peri and postmenopausal women advised to take Livial were studied for persistency, efficacy and side effect of treatment. RESULTS: The mean age is 55.2 years old and post menopausal period is averaged 6.7 years. Their chief complaints were mainly climacteric symptoms(97.0%). Ninety percent of women took livial after prescription. 41.0% of women ceased the therapy after (0.7 +/- 0.8) years of treatment, while 26.2% of them restored after (0.3 +/- 0.2) years due to recurrence of symptoms. The major reason of cease was fear of cancer. The climacteric symptoms were well relieved while body mass index remained unchanged. The occurrence of vaginal bleeding, breast tenderness, edema and gastrointestinal symptoms was 5.6%, 19.7%, 8.2% and 9.0% respectively. The side effect was dose dependent. CONCLUSION: Postmenopausal women had well compliance to Livial despite of mild side effects and ceasing ratio. PMID- 11776165 TI - [Changes of nitric oxide and endothelin plasma levels and effects of hormone replacement therapy in postmenopausal women]. AB - OBJECTIVES: To investigate the changes of plasma levels of nitric oxide(NO) and endothelin (ET) when the estrogen level dropped and to assess the effects of hormone replacement therapy (HRT) on NO, ET plasma levels in postmenopausal women. METHODS: Twenty-six women with regular menses (regular mense group), twenty-eight perimenopausal women with climacteric symptoms (perimenopausal group), seventy healthy postmenopausal women (postmenopausal group) were in duded in this study. Thirty postmenopausal volunteers received oral conjugated estrogen/medroxyprogesterone acetate (post menopause group I) and twenty others took only calcium (post menopause group II) for 6 months. Plasma NO, ET, follicle stimulation hormone (FSH) and estradiol (E2) levels were measured for all the women. RESULTS: The levels of NO were significantly lower in perimenopausal group (23.8 +/- 15.1) mumol/L and postmenopausal group (20.0 +/- 12.1) mumol/L than those of regular mense group (33.2 +/- 15.5) mumol/L (P < 0.05, P < 0.01). The mean concentrations of ET were significantly higher in both of perimenopausal (59.3 +/- 14.2) pg/L and postmenopausal groups (65.3 +/- 16.2) pg/L than those of regular mense group (51.1 +/- 15.6) pg/L (P < 0.01). Plasma NO (32.9 +/- 16.1) mumol/L and E2(47.5 +/- 12.9) pg/L values were significantly higher, and ET (52.2 +/- 12.0) pg/L values significantly lower than baselines of NO (20.3 +/- 11.1) mumol/L, E2(7.9 +/- 4.8) ng/Land ET(62.6 +/- 18.9) pg/L, respectively, in menopause group I after treatment for 6 months (P < 0.01). There was no difference in NO, ET and E2 concentrations in menopause group II before and after taking calcium for 6 month (P > 0.05). E2 had a significant positive correlation with NO and significant negative correlation with ET and FSH. CONCLUSIONS: HRT results in an increased level of NO and decreased level of ET in postmenopausal women. This may be one of the mechanisms by which HRT provides cardiovascular benefit. PMID- 11776166 TI - [Study on the relationship between CD44v6, p53 gene mutation and ovarian carcinoma metastasis]. AB - OBJECTIVE: To explore the relationship between CD44v6 expression, p53 gene mutation, cell ploidy and ovarian metastasis. METHODS: Eighty-five ovarian specimens (20 normal specimens, 20 benign tumors, 20 non-metastatic carcinomas and 25 metastatic carcinomas) were collected. Cell ploidy and the distribution of cell population in each stage of cell cycle were detected by flow cytometry. By using techniques such as reverse transcription-polymerase chain reaction, southern blot and image analysis, the quantitative and qualitative expression of CD44v6 were determined; the mutation of p53 gene in the ovarian specimens was also determined by polymerase chain reaction-single strand conformation polymorphism with silver staining. RESULTS: In the normal ovarian specimens, benign tumors, non-metastatic and metastatic carcinomas, the positive rates of CD44v6 expression and p53 gene mutation were 0%, 10%, 75%, 88% and 0%, 5%, 40%, 60%, respectively, both increased gradually. The mean dark density in the non metastatic (3,820 +/- 289) and metastatic (10,132 +/- 1,521) groups was significantly different (P < 0.01). In the positive and negative CD44v6 ovarian carcinoma groups, the mean carcinoma cell percentage at the G2M stage was 5.90% and 5.06% (P > 0.05), mean aneuploidy carcinoma cell percentage was 57% and 50% (P > 0.05) respectively. In the mutated and non-mutated p53 gene groups, their mean cell population at the G2M stage was 11.15% and 5.85% (P < 0.05), mean aneuploidy carcinoma cell percentage was 74% and 36% (P < 0.05), respectively. CONCLUSIONS: The expression of CD44v6 is closely related to carcinoma metastasis. The relationship between CD44v6 expression, p53 gene mutation and carcinoma metastasis can be involved in the different mechanism. As compared to mutated p53 gene, CD44v6 appears to be more suitable as a metastatic marker. PMID- 11776167 TI - [Growth inhibition effect of 5-aza-CdR on endometrial carcinoma xenografted in nude mice by p16 gene demethylation]. AB - OBJECTIVE: To study the antitumor effect and mechanism of 5-aza-CdR on endometrial carcinoma xenografted in nude mice. METHODS: The effects of 5-aza-CdR on tumor growth inhibition were observed on human endometrial carcinoma xenografted in nude mice. The methylation status of the 5' CpG island of the p16 gene was evaluated using methylation-sensitive restriction enzymes and polymerase chain reaction. p16 mRNA expression was determined by reverse transcription polymerase chain reaction. RESULTS: The inhibition rates of the tumor were 79.10% in 5-aza-CdR group (P < 0.01), 90.32% in 5-aza-CdR + DDP group (P < 0.01), and 10.13% in DDP group (P > 0.05), respectively, in comparison with control group. The methylation level of p16 gene was gradually decreased and the p16 mRNA expression restored after exposure to 5-aza-CdR. CONCLUSION: Our data show that 5 aza-CdR may inhibit tumor growth by reactivating growth-regulatory gene silenced by de novo methylation. PMID- 11776168 TI - [Study on immunity of endometriosis]. PMID- 11776169 TI - [Study on interferon gamma and interleukin-4 contents of plasma and cultured monoclear cell supernatants in patients with endometriosis]. AB - OBJECTIVE: To investigate the cytokin production of T helper cell (Th) 1, Th2 subsets in patients with endometriosis(EM). METHODS: The cytokine production of Th1, Th2 cells expressed by interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) contents respectively in supernatants of cultured PHA induced peripheral blood mononuclear cell (PBMC) and plasma, obtained from 30 EM patients and 15 normal controls were determined by enzyme linked immunoabsorbent assay (ELISA). RESULTS: IL-4 contents of EM patients were elevated both in plasma and PBMC supernatants[(32.0 +/- 22.6) ng/L and (32.8 +/- 12.5) ng/L, respectively], while IFN-gamma levels was suppressed in PBMC supernatant as compared with normal controls [(1,095.6 +/- 375.6) ng/L and (1,549.3 +/- 361.9) ng/L, respectively] (P < 0.01, P < 0.05). As a results, the ratio of IFN-gamma/IL-4 decreased in EM patients. CONCLUSIONS: Changes of IFN-gamma and IL-4 contents in EM patients may reflect functional inbalance between Th1 and Th2 cells, which may play a role in the pathogenesis of EM. PMID- 11776170 TI - [Measurements of interleukin-6, interleukin-8 and transforming growth factor-beta 1 levels in peritoneal fluid of patients with endometriosis]. AB - OBJECTIVE: To investigate the role of cytokines in peritoneal fluid on pathogenesis of endometriosis (EM). METHODS: Interleukin-6 (IL-6), interleukin 8(IL-8) and transforming growth factor-beta 1 (TGF-beta 1) contents in peritoneal fluid (PF) of 31 cases with EM were detected by enzyme linked immunoabsorbent assay (ELISA) and compared with the counterparts of 22 cases without EM (controls). The correlation analyses between cytokine concentrations in peritoneal fluid of EM patients and the severity of EM or dysmenorrhea score were performed. RESULTS: The peritoneal fluid from patients with EM contained significantly greater amounts of IL-6 [(1.8 +/- 0.4) ng/L] and IL-8 [(1.7 +/- 0.5) ng/L] than those in controls [(1.2 +/- 0.2) ng/L and (1.4 +/- 0.3) ng/L respectively, P < 0.05]. However, in the amounts of TGF-beta 1 there were no significant difference (P > 0.05) between the two groups. The highest PF IL-6 and IL-8 concentrations were found in stage II, III and stag I, II EM respectively. A significant correlation between PF IL-6 content and the severity of disease was noted but there were no evidences of a relationship between concentrations of IL 8 and TGF-beta 1 and the severity of EM as well as between concentrations of three cytokines and dysmenorrhea score. CONCLUSION: Unusual levels of IL-6 and IL 8 in PF of EM patients partly account for imbalance of the immunologically dynamic environment in peritoneal cavity of EM patients. PMID- 11776171 TI - [Changes of tumor necrosis factor alpha and interleukin-6 levels in peritoneal fluid of patients with endometriosis and their effects on human sperm motility and mouse embryo development]. AB - OBJECTIVE: To study the changes of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels in peritoneal fluid of patients with endometriosis and their effects on human sperm motility and mouse embryo development. METHODS: Levels of TNF-alpha and IL-6 in peritoneal fluid and cultured peritoneal macrophages supernatant were detected by enzyme-linked immunoassay (ELISA) in 14 infertile patients (EMT group) with endometriosis proven by laparoscopy and 11 infertile women with normal pelvic organs (control group). The effects of peritoneal fluids obtained from the 2 groups on human sperm motility and development of 2-cell mouse embryo were also studied in vitro. RESULTS: In EMT group the numbers of peritoneal macrophages were higher than those in the control group. Levels of TNF-alpha [(0.33 +/- 0.15), (7.19 +/- 0.60) micrograms/L] and IL 6 [(0.49 +/- 0.68), (1.51 +/- 0.08) micrograms/L] in peritoneal fluid and peritoneal macrophage supernatant were also elevated significantly as compared with those in the controls (P < 0.01). Meanwhile, after four-hour incubation with peritoneal fluids, the percentage of straight-line moving sperm and total sperm motility rate were decreased significantly in EMT group(P < 0.01). Appearance rate of 16-cell mouse embryo was 32.5% in EMT group versus 47.6% in control group after 48 hour coculture with peritoneal fluids(P < 0.01). CONCLUSION: It is likely that elevation of peritoneal fluids cytokines levels in patients with endometriosis may play a role in the pathogenesis of infertility associated with endometriosis. PMID- 11776172 TI - [Study on apoptosis and its related genes in pregnancy induced hypertension]. AB - OBJECTIVE: To investigate apoptosis and its related genes expression in serious pregnancy induced hypertension (SPIH). METHODS: 40 cases of normal term pregnancy(NTP) and 40 cases of SPIH were enrolled in this study. Apoptosis was detected using DNA in situ terminal deoxynucleotidyl transferas (TDT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick ending labeling (TUNEL); bax and bcl 2 were detected by immunohistochemical staining (SP). RESULTS: In NTP group apoptosis index(AI) of cytotrophoblasts(CT) and syncytiophoblasts(ST) in placenta was (1.1 +/- 0.9)% and (41.8 +/- 1.5)%; bax positive rate was (1.0 +/- 0.9)% and (28.9 +/- 9.7)%; bcl-2 was (2.2 +/- 0.8)% and (22.9 +/- 0.7)% respectively; bax/bcl-2 was 0.7-1.7. In SPIH group, AI was (4.3 +/- 1.2)% and (45.3% +/- 1.4)%; bax was (2.2 +/- 0.8)% and (42.5 +/- 11.7)%; bcl-2 was (3.2 +/- 0.8)% and (23.3 +/- 7.8)%; bax/bcl-2 was 1.0-3.2. The difference between SPIH and NTP was significant respectively (P < 0.01); bax/bcl-2 was balance in NTP, while the balance was broken in SPIH. CONCLUSIONS: Apoptosis and its related genes expression are simultaneous. The balance and imbalance of apoptosis and bax/bcl-2 affect the structure and the function of placenta, and then may further affect the outcome of pregnancy. PMID- 11776173 TI - [Retrospective analysis of 266 cases of pregnancy complicated by heart disease]. AB - OBJECTIVE: To investigate the influence of cardiac function of pregnant women on outcome of their pregnancies. METHODS: Clinical data of 266 cases of pregnant women with heart diseases from January, 1993 to March, 1999 were analyzed retrospectively. RESULTS: (1) The highest incidence of cardiac disease with grade I to II of heart function was due to myocarditis, sequelae of myocarditis and abnormal cardiac rhythm (179 cases, 67.29%). The incidence of congenital heart disease is on the second (41 cases, 15.41%) which is higher than that of rheumatic heart disease (28 cases, 10.91%). (2) Grade III and IV cardiac function was mainly related to congenital and rheumatic heart diseases during pregnancy. The rate of grade I/II heart function in pregnant women after heart operations was 95.45%. (3) The incidence of premature delivery, low weight of newborns and perinatal mortality of mother were higher in women with grade III and IV heart function than in those with grade I and II heart function. CONCLUSIONS: The incidence of myocarditis and sequelae of myocarditis is increasing. Pregnancies complicated with congenital and rheumatic heart diseases are still major causes of perinatal morbidity and mortality of mother and baby. Heart operation can obviously improve the heart function. More effective managements should be adopted. PMID- 11776174 TI - [Effects of elective cesarean section and antibiotics to the bacterial flora in female genital tract]. AB - OBJECTIVE: To study the effects of elective cesarean section and antibiotics to the bacterial flora in the normal female genital tract. METHODS: Forty-five cases of elective cesarean section were randomly divided into 3 groups: no antibiotic was given (group A), one antibiotic was given for three days (group B), and only once antibiotic was used (group C). Bacterial cultures of vaginal swab and specimens aspirated from uterine cavity were performed in each case before and after operation to supervise the changes of bacterial flora in genital tract and postoperative infection. RESULTS: The positive rate of bacterial culture was 35.71% before operation but 64.29% after operation (P < 0.01). The numbers of aerobe and anaerobe were 3 and 10 strains, respectively, before operation, and 16 and 18 strains after operation. The counts of anaerobe were more than those of aerobe in group A either before or after operation in group A. The counts of aerobe, on the other hand, were more than those of anaerobe both in group B and C after operation. The rates of positive bacterial culture in uterine cavity after operation were similar among the three groups (P > 0.05). Interestingly the operative infection rates were 6.67% evenly. CONCLUSIONS: Both cesarean section and antibiotics may disturb the bacterial flora in the normal female genital tract. The disturbance may increase the chance for flora imbalance and the postoperative infection. There was a great need for rational application of prophylactic antibiotics after cesarean section. Single-dose antibiotic during cesarean section should be advocated. PMID- 11776175 TI - [Change of plasma cellular fibronectin values in hypertension disorders of pregnancy]. AB - OBJECTIVE: To investigate change of plasma values of cellular fibronectin (cFN) in pregnant women with hypertension diseases. METHODS: One hundred and twelve pregnant women were assigned into five groups according to definition of hypertension diseases in pregnancy published by the National Working Group on Hypertension. The values of plasma cFN were measured with enzyme-link immunosorbent assay (ELISA). Statistical tests were performed with Variance Analysis (Scheff's post-hoc). RESULTS: Plasma cFN values in women of preeclamptic group (12.25 +/- 4.00) mg/L and superimposed preeclamptic group (11.33 +/- 3.74) mg/L were both significantly higher than those of normal group (5.06 +/- 1.33) mg/L (P < 0.01). However, cFN values were not statistically different between women of chronic hypertension or transient hypertension and of normal women (P > 0.05). CONCLUSION: The clinical detection of plasma cFN values appears to be useful in differentiating various hypertension diseases of pregnancy and in selection of relevant treatment regimen. PMID- 11776176 TI - [Expression of basic fibroblastic growth factor and microvessel density in endometrial carcinoma]. AB - OBJECTIVE: To investigate the relation of basic fibroblastic growth factor (bFGF) and microvessel density (MVD) with endometrial carcinoma. METHODS: A total of 66 specimens of endometrial carcinoma were evaluated by immunohistochemical technique with polyclonal antibody against bFGF. The microvessels were highlight by immunohistologically staining to detect factor VIII-related antigen. The area of the deepest myometrial invasion was selected for staining. Ninteen specimens of uterine prolapse were used for control. RESULTS: Expression of bFGF was significantly correlated with tumor grade (P < 0.01). MVD was positively correlated with age, tumor grade and myometrial invasion (P < 0.01, respectively). MVD was significantly correlated with expression of bFGF (P < 0.01). Patients with bFGF strong expression and high MVD (> or = 9.4) had worse prognosis (P < 0.01, respectively). CONCLUSIONS: bFGF plays important role in angiogenesis in endometrial carcinoma. Expression of bFGF and MVD could be used as prognostic factors for survival in endometrial carcinoma. PMID- 11776177 TI - [In vitro studies on dendritic cell derived from cord blood and its role in antitumor immunity]. AB - OBJECTIVE: To investigate the way of inducing dendritic cell (DC) from precursor in cord blood and its role in antitumor immunity. METHODS: Cord blood was collected under sterile condition and the mononuclear cells (MNCs) were separated by centrifugal in density gradient (Ficoll-Hypaque). The adhesion cells, collected among the MNCs, were cultured with interleukin-4 (IL-4, 50 ng), granulocyte-macrophage colony-stumilating factor (GM-CSF, 100 ng) and tumor necrosis factor alpha (TNF-alpha, 1-2 ng) in dulbecco's modified eagles medium (DMEM) medium. Cell phenotype was analyzed on 10th day with CD1a, CD16, CD14, CD19, CD40, CD56, CD80, CD83, and human leukocyte antigens-D-related (HLA-DR) antibody by using indirect immunofluorescence assays. After cultured with tumor cytolysis antigen for 2 days, the cells were incubated with auto T cell separated by E-rosette formation. Methyl thiazolyl tetrazolium (MTT) assay was employed to test inhibition rate of tumor specific cytotoxic T lymphocyte (CTL) on HO9810 tumor cell line. RESULTS: Our results indicated that DC precursors in cord blood can be induced to differentiate and mature in the medium containing IL-4, GM-CSF, and TNF-alpha. Some DC specialized antigens expressions were seen on 10th day after cultured with cytokines. After incubation with tumor cytolysis antigen, the DC can activate the CTL to become tumor specialized CTL, which had shown significantly inhibition on growth of HO9810 tumor cell line. CONCLUSIONS: Primary in vitro experiment has shown that the precursors in cord blood can be induced to functional DC which activate T lymphocyte to become tumor specialized CTL. Our result indicate that it is an efficient and convenient way in antitumor immunity by inducing DC precursors in cord blood to functional DC and may have a great implication on clinical application. PMID- 11776178 TI - [Study on the anti-mullerian hormone served as a marker for granulosa cell tumor of ovary]. AB - OBJECTIVE: To probe the experimental basis for anti-mullerian hormone(AMH) served as a specific tumor label in diagnosis of granulosa cell tumor(GCT) of ovary. METHODS: The expression of AMH and its receptor mRNA in early and late GCT of ovary in transgenic mice was studied by using immunohistochemistry, in stiu hybridization and Northern hybridization. Furthermore, the expression of AMH and its receptor mRNA in cultured GCT cells was also determined by using radioiodine labeling method and Northern hybridization. RESULTS: In the early ovary GCT of transgenic mice, immunohistochemistry showed that AMH was positively stained as brownish yellow granulars, which were located in the cell membrane of the tumor, in situ hybridization showed its receptor mRNA was positive as blue granulars, which were also located in the cell membrane. The positive rate of both AMH and its receptor mRNA was 100%. Results by northern hybridization also showed that the positive rate of AMH and its receptor mRNA in the early ovary GCT and GCT cells was 100%. Radioautography indicated that there was a radioactive bright point, the binding rate of 125I labeled AMH with tumor cells reached 100%. CONCLUSIONS: AMH can be served as a specific tumor marker in the diagnosis of difficult and complicated tumors of ovary, and in the diagnosis, treatment and follow-up survey of the early GCT. PMID- 11776179 TI - [Focus on leptin studies in the field of obstetrics]. PMID- 11776180 TI - [Serum leptin levels in normal pregnant women and their babies]. AB - OBJECTIVE: To investigate serum leptin levels in normal pregnant women and their babies. METHODS: Immunoradioassay was used to measure the serum levels of leptin in 10 non-pregnant women, 63 pregnant women (31 in the firs, 10 in the second, and 22 in the third trimester), 27 women at delivery, 18 women in the first week after delivery and in 18 newborns' cord serum. Serum leptin levels were correlated with body weight, body mass index (BMI), fasting insulin levels and lipids. RESULTS: Serum insulin, cholesterol, triglyceride were increased since the second trimester during pregnancy. One week after delivery serum insulin but not cholesterol and triglicetride level was decreased to the levels of non pregnancy. Serum leptin levels were (7.98 +/- 4.42) micrograms/L in non-pregnant women and (7.03 +/- 3.42) micrograms/L in the first trimester. Then the levels were increased to (13.97 +/- 8.03) micrograms/L in second trimester and (14.86 +/ 6.25) micrograms/L in the third trimester, (19.89 +/- 9.66) micrograms/L at the delivery time and returned to (10.86 +/- 9.18) micrograms/L in the first week after delivery, respectively. Cord serum leptin levels of newborns were (8.93 +/- 6.95) micrograms/L. Serum leptin levels in pregnant women were positively correlated with their body weight, BMI, fasting serum insulin and glycerol levels. Cord serum leptin levels was positively correlated with newborn birth weights as well as their insulin levels. CONCLUSIONS: (1) Serum leptin levels increase in the second and third trimester, and may contribute to the inhibition of increased food intake, body weight and body fat. (2) Newborn serum leptin may come from themselves, and the levels were lower than those in their mothers. (3) Birth weight, possibly adiposity, as well as serum insulin positively regulates serum leptin levels in neonates as in adults. PMID- 11776181 TI - [Study on relationship between levels of leptin in maternal blood, amniotic fluid, and umbilical blood and newborn's weight]. AB - OBJECTIVE: To explore the relationship between leptin's quantity in maternal blood, amniotic fluid, umbilical blood and maternal and newborn's weights. METHODS: Levels of leptin in maternal blood, amniotic fluid, and umbilical blood of 34 pregnant women were detected by radioimmunoassay (RIA) method. Results were analyzed by the correlative analysis. RESULTS: (1) Leptin can be detected either from maternal blood or amniotic fluid or umbilical blood. (2) There was an obvious correction between newborn's weight and leptin's quantity of maternal blood (relative coefficient r = 0.53, P < 0.01), amniotic fluid (r = 0.73, P < 0.01) and umbilical blood (r = 0.67, P < 0.01). (3) There was an obvious correction between maternal weight and leptin's quantity of maternal blood (r = 0.61, P < 0.01). (4) There was an obvious correction between leptin's quantity of amniotic fluid and umbilical blood (r = 0.72, P < 0.001). (5) There was not obvious correction between maternal weight and leptin's quantity of amniotic fluid and umbilical blood (r = 0.22, r = 0.18, respectively. P > 0.05). CONCLUSION: It may be of important significance in detection of leptin's quantity in amniotic fluid and maternal blood in pregnant women for predicting the weight and growth of newborns. PMID- 11776182 TI - [Serum leptin levels during pregnancy]. AB - OBJECTIVE: To study the serum leptin levels in Chinese pregnant women, and to discuss the relationship between leptin level and pregnancy. METHODS: Serum leptin concentrations of 251 pregnant women (13.6 to 30.9 gestational weeks) were measured with radioimmunoassay, and 35 age and body mass index (BMI) matched non pregnant women were selected as control. Serum leptin concentrations were compared between pregnant and control women, correlations between leptin concentrations and gestational age, weight, BMI, blood pressure and other parameters were analyzed. RESULTS: In these pregnant women, aged (28.5 +/- 3.9) years, BMI (23.6 +/- 2.8) kg/m2, serum leptin concentrations were (15.1 +/- 7.4) micrograms/L; while in control women, aged (27.4 +/- 3.8) years, BMI (22.6 +/- 2.5) kg/m2, serum leptin concentrations were (9.1 +/- 4.9) micrograms/L. The mean age and BMI are comparable between 2 groups. Serum leptin concentrations in pregnant women were much higher than those in control women (P < 0.001). Within the pregnant women, serum leptin concentrations were significantly correlated to body weight(r = 0.529), BMI (r = 0.551,), waist circumference (r = 0.564), height of uterus bottom (r = 0.151), systolic blood pressure (r = 0.134) and diastolic blood pressure (r = 0.251). During pregnancy, serum leptin concentrations rose along with the gestational age, although no statistical difference was revealed up to 30th gestational week. CONCLUSIONS: Leptin is a hormone intimately related to the pregnancy, its concentrations are much higher during pregnancy than those of non-pregnant women with matched age and BMI. Like in non-pregnant women, leptin levels are significantly correlated to body weight and BMI, and also correlated to blood pressure, the correlation between leptin and diastolic blood pressure is more evident, indicating that serum leptin may serve as a marker for detecting and monitoring pregnancy complications. PMID- 11776183 TI - [The effect of plasma from women with preeclampsia on endothelial cells activators in vitro]. AB - OBJECTIVE: To study the effect of plasma from women with preeclampsia on endothelial cell activators in vitro and determine whether factor(s) in the plasma of women with preeclampsia induces activation of vascular endothelial cells. METHODS: Twenty women with preeclampsia and 15 normal ones at late trimester of pregnancy were studied, from whom maternal venous blood samples were collected. Plasma 6-keto-PGF1 alpha, the end products of prostacyclin (PGI2) and TXB2, the end products of thromboxane A2(TXA2), were measured by radioimmunoassay. Plasma from women with preeclampsia or from normal women at late trimester was added to the bovine pulmonary microvessel endothelial cells in vitro. Twenty-four hours later, levels of 6-keto-PGF1 alpha produced by cultured endothelial cells were measured. RESULTS: The mean values of 6-keto-PGF1 alpha in matrnal venous plasma were (94.49 +/- 25.23) ng/L in preeclamptic group and (248.81 +/- 51.99) ng/L in normal pregnant group. Plasma TXB2 values were (104.61 +/- 13.12) ng/L in preeclamptic group and (66.26 +/- 38.80) ng/L in normal pregnant group. TXB2/6-keto-PGF1 alpha ratios were (1.11 +/- 0.03) in preeclamptic group and (0.28 +/- 0.02) in normal pregnant group. Maternal plasma values of 6-keto-PGF1 alpha were lower in peeclamptic group than those of normal pregnant group (P < 0.01). On the other hand, plasma TXB2 values were higher in preeclamptic group than in normal pregnant group (P < 0.01). TXB2/6-keto-PGF1 alpha ratios, however, were significantly different between the two groups (P < 0.01). The values of 6-keto-PGF1 alpha produced by cultured endothelial cells exposed to 2% plasma were (1,363.00 +/- 99.16) ng/L in preeclamptic group and (819.49 +/- 96.62) ng/L in normal pregnant group (P < 0.01). CONCLUSIONS: PGI2 and TXA2 may play an important role in preeclampsia. Plasma from women with preeclampsia could stimulate the production of prostacyclin in cultured endothelial cells in vitro. PMID- 11776184 TI - [Reinsemination by intracytoplasmic sperm injection 24-hour after conventional in vitro fertilization failure]. AB - OBJECTIVE: To examine the efficacy of intracytoplasmic sperm injection (ICSI) for rescue of conventional in vitro fertilization (IVF) failure. METHODS: From June 1997 to October 1998, 17 women with non-male factor infertility undergoing conventional ovarian hyper-stimulation protocol and IVF in our center, with fertilization failure were reinseminated by ICSI. RESULTS: Intracytoplasmic sperm injection of 130 unfertilized mature oocytes resulted in degeneration in 25 oocytes, successful fertilization occurred in 100 (76.9%) of the survival oocytes, and embryo transfer were done in 18 cycles. Two viable pregnancies resulted. CONCLUSION: If chromosome abnormalities of embryos arising from reinsemination were ignored, our results suggest that ICSI is a successful means of rescuing conventional IVF failure. PMID- 11776185 TI - [Influence of sonographic examination on embryo villi during early pregnancy]. AB - OBJECTIVE: To evaluate the effects of sonographic examination on embryo villi during early pregnancy. METHODS: Eighty early pregnant women intended for artificial abortion were divided into 4 groups: group I served as control, the remaining 3 groups underwent pelvic sonographic examination transabdominally for 10 minutes (group II), transvaginally for 3 minutes (group III) or for 10 minutes (group IV) respectively. After 1 hour embryo villi were obtained through artificial abortion and examined by electronic microscopy, biochemical methods and sister chromatid exchanges (SCE). RESULTS: In group IV, but not group II, III, the embryo microvilli were found broken, lost and disarranged. The rough endoplasmic reticulum of trophoblasts expanded. Their malondial dehyde levels increased while the superoxide dismutase (SOD) decreased as compared with control (P < 0.01). There was no difference of SCE among these 4 groups. CONCLUSION: It is recommended that sonographic examination should be done through abdominal approach for shorter than 10 minutes during early stage of pregnancy. PMID- 11776186 TI - [Advances in diagnosis and treatment of ectopic pregnancy during the past ten years]. AB - OBJECTIVE: To investigate the changes of diagnosis and treatment of ectopic pregnancy (EP) during the past ten years. METHODS: Medical records of 1,970 cases with EP seen in our hospital from Jan. 1987 to Dec. 1996 were collected and analyzed retrospectively. RESULTS: (1) The incidence of EP increases from 1.0 per 42.4 labours during 1987-1988 to 1.0 per 6.6 labours in 1995-1996. (2) Diagnosis was confirmed more by television laparoscopy, transvaginal ultrasonography and sensitive human chorionic gonadotropin-beta subunit assay rather than loparotomy and with a shorter period, (6.5 +/- 0.7) days in 1987-1988 versus (3.7 +/- 0.2) days in 1995-1996. (3) The choice of treatment was more conservative or through laparoscopic surgery than abdominal salpingectomy. (4) The success rate of conservative surgery expectant management reached 100.0% and medical treatment with a variety of choices around 80.0%-85.%. CONCLUSIONS: Although the incidence of EP increased, with the improvement of diagnostic approaches, patients were detected at an earlier stage and possible to be treated more conservatively. PMID- 11776187 TI - [Determination of tumor necrosis factor-alpha and interleukin-6 levels of the tubal fluids in patients with infertility caused by infection of Chlamydia trachomatis]. AB - OBJECTIVE: To study the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in tubal fluids of tubal factor infertile (TFI) women due to chlamydia trachomatis (CT) infection and its implication. METHODS: Twenty-two TFI women with CT infection (group A), twenty-three TFI women without CT infection (group B) and nineteen fertile women with normal tubes (group control) were enrolled for study. Levels of TNF-alpha and IL-6 in tubal fluids were measured by enzyme-linked immunosorbent assay. RESULTS: Group A had significantly higher TNF alpha levels than those of group control (178 ng/L versus 124 ng/L, P < 0.01). Moreover, women with tubal blocks had significantly higher TNF-alpha those of tubal adhesions (199 ng/L versus 142 ng/L, P < 0.01). IL-6 levels of group A were significantly higher than those of group B and group control (681 ng/L versus 264 ng/L and 229 ng/L, both P < 0.01), but there is no difference between group B and group control. CONCLUSIONS: Local TNF-alpha and IL-6 levels increased in silent tubal infection of CT. TNF-alpha had a positive relevance with the degree of tubal damage. PMID- 11776188 TI - [Effects of estrogen on serum lipids, plasma endothelin-1, atherosclerosis in ovariectomized rabbits]. AB - OBJECTIVE: To investigate the effects of estrogen on serum lipids, plasma endothelin-1(ET-1) and atherosclerosis in ovariectomized(OVX) rabbits. METHODS: Forty-five female rabbits were randomly divided into 5 groups, there are 9 in each: group A: normal control; group B: sham operation + cholesterol feeding; group C: OVX + cholesterol feeding; group D: OVX + cholesterol feeding + estradiol benzoate; group E: OVX + cholesterol feeding + estradiol valerate. The OVX rabbits fed with cholesterol were used as a model for atherosclerosis. After fed for 12 weeks, all rabbits were sacrificed, and the levels of serum lipids, plasma ET-1, atherosclerosis plaque of aorta were measured. RESULTS: (1) Similar with group B, the total cholesterol (TC) of group D and E [(24.95 +/- 5.31) mmol/L and (27.53 +/- 13.18) mmol/L respectively], were significantly decreased as compared with group C which was (37.69 +/- 4.16) mmol/L. (2) The plasma ET-1 level of group C, which was (343.37 +/- 106.10) ng/L, was significantly higher as compared with group D and E, which were (262.19 +/- 36.45) ng/L [symbol: see text] (245.37 +/- 35.76) ng/L respectively. (3) There were no statistically differences of lipidic sedimentation area among group D, E, and B, which were (17.30 +/- 5.44)% and (36.99 +/- 20.29)% and (29.03 +/- 9.67)% respectively. All of them were significantly decreased as compared with group C, which was (74.83 +/- 12.58)%. CONCLUSION: Estrogen may improve the serum lipids, decrease the plasma ET-1 level, and prevent the atherosclerosis of ovariectomized rabbits. PMID- 11776189 TI - [Establishment of in vitro serum-free embryo implantation model]. AB - OBJECTIVE: To observe the growth and implantation of mouse embryos in vitro. METHODS: In order to establish a serum-free coculture system, the whole components of decidual tissue was collected and cultured in vitro. Then 4-day mouse embryos were added to the well-developed decidual cells, and the following changes of the above system were closely observed under microscope. RESULTS: Mouse embryos were successfully hatched, adhered, implanted and outspreaded under the coculture system. The extraplacental cone and amniotic sac were formed as well. Decidual cells kept stable during the following 4-day coculture. CONCLUSIONS: Decidual cell is an ideal feeder cell for coculture. Our results showed that the modified method of decidual cell culture and the establishment of implantation model were simple, practical and reliable. PMID- 11776190 TI - [Analysis of the clinical characteristics and prognostic factors with primary normal-sized epithelial ovarian carcinoma syndrome]. AB - OBJECTIVE: To investigate the clinical characteristics and prognostic factors of the primary normal-sized epithelial ovarian carcinoma syndrome. METHODS: The clinical records and pathologic slides of the 10 patients who satisfied the diagnostic criteria were retrospectively analyzed. RESULTS: The primary normal sized epithelial ovarian carcinoma syndrome was detected in approximately 1.92% of the patients with the epithelial ovarian carcinoma. The age of the patients at diagnosis ranged from 43-70 years, with a median age of 57 years. The most common presentations included anorexia, increasing abdominal girth and awareness of abdominal or pelvic mass. During the exploratory laparotomy although we often discovered the diffuse metastasis throughout the abdominal and pelvic cavity, the ovaries both appeared normal size and had a fine granularity on the external surface. The survival time of patients with remained tumors smaller than 2.0 cm was longer than those with remained tumors larger than 2.0 cm, but the Log-rank evaluation indicated chi 2 = 0.61, P > 0.05. The patients who underwent postoperative chemotherapy have been noted to achieve some long-term survival. The median survival time was 20 months. CONCLUSION: The results predict that the size of the remained tumors may be one of the important factors to the survival and the disease is sensitive to the postoperative chemotherapy. PMID- 11776191 TI - [The effect of progesterone on proliferation and apoptosis in ovarian cancer cell]. AB - OBJECTIVE: To investigate the regulatory effect of progesterone on proliferation and apoptosis in ovarian cancer cell line HO8910 in vitro. METHODS: Ovarian cancer cell line HO8910 originated from human ovarian serous cystadenocarcinoma was cultured in vitro. Two groups were set up: study group (progesterone in different concentrations) and control group without progesterone. Cell proliferation was measured by 3-(4, 5-dimethylthiazol-z-yl)-2,5-dipheny tetrazolium blue (MTT) colorimetric assay. Cell cycle and apoptotic percentage were detected by flow cytometry, morphological changes of apoptotic cells were observed by light and electron microscopy, and apoptotic cells were quantitatively determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). In addition, expression of intracellular bcl-2 protein was analyzed by flow cytometric indirect immunofluorescent technique. RESULTS: Progesterone of 1 x 10(-7)-1 x 10(-5) mol/L inhibited HO8910 cell growth significantly in a dose-dependent manner (P < 0.01). After treatment with progesterone, the enhanced G0/G1 arrest was accompanied with the enhanced apoptotic peak and percentage, as well apoptotic cells were found more than those in control group (P < 0.05). By light and electron microscopy, there were many morphological characteristics of apoptosis including compaction and margination of nuclear chromatin, nuclear fragments, and apoptotic bodies. Analysis on expression of intracellular bcl-2 protein showed that progesterone could down regulate bcl-2 protein and at concentration of 1 x 10(-5) mol/L it could almost block bcl-2 expression. CONCLUSIONS: It is suggested in the present study that progesterone can inhibit the proliferation of epithelial ovarian cancer cells in vitro and there is an accordant dose-response relationship. Its anticancer effect seems to be due to induction of apoptosis which maybe a result of down-regulation of the anti-apoptotic protein bcl-2. PMID- 11776192 TI - [Effects of human interleukin-2 gene transfer on the immunity of ovarian cancer cell line SKOV3]. AB - OBJECTIVE: To study the effect of interleukin-2 (IL-2) gene transfer on the immunity of ovarian cancer cell line SKOV3. METHODS: The expression of main histologic complex (MHC) molecular HLA-ABC, HLA-DR and HLA-DQ of SKOV3, SKOV3/Neo and SKOV3/IL-2 cells were detected by flow cytometry. The 51Cr-4 hr releasing test was employed to detect the killing effects of natural killer (NK) and lymphokine-activated killer (LAK) cells. Meanwhile, the tumor cell and lymphocyte co-culture was performed. RESULTS: The expression of HLA-ABC, HLA-DR and HLA-DQ molecular of hIL-2 gene modified cells was upregulated markedly. The 51Cr-4 hr releasing test showed that the parental and gene modified cells were markedly resistant to NK cells, but the IL-2 gene modified cells was more sensitive to LAK cells. There were significant differences between them (P < 0.01). The "cross talk" of tumor cell with lymphocyte was observed when the hIL-2 gene modified SKOV3 cells were cocultured with lymphocyte. CONCLUSION: IL-2 gene transfer can enhance the immunity of ovarian cancer cell line SKOV3. PMID- 11776194 TI - [The current status and the future of preimplantation genetic diagnosis]. PMID- 11776193 TI - [Clinical study on effect of Tripterygium wilfordii Hook. f. on uterin leiomyoma]. AB - OBJECTIVE: To observe the therapeutic effect of Tripterygium wilfordii Hook. f. on patients with uterine leiomyoma. METHODS: Baseline ultrasound examinations of myomas and uterine were obtained and repeated three months, six months after treatment. Blood samples were collected in the mid-follicular or mid-luteal phase of the menstrual cycle before initiation of Tripterygium wilfordii Hook. f. therapy and after treatment 3-4 months and 5-6 months, for determination of estradiol, progesteron, testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin by radioimmunoassay. RESULTS: Significant decrease in leiomyoma volume was detected in 39 of 65 (60.0%) patients after 3-4 months of Tripterygium wilfordii Hook. f. treatment and 28 of 40 (70.0%) patients after 5-6 months of treatment. The decrease in leiomyoma volume with Tripterygium wilfordii Hook. f. treatment was time-dependent while 27.84% in 3-4 months, 51.6% in 5-6 months. 25 of 65 patients were amenorrheic during the course of treatment. Compared with pretreatment values, Tripterygium wilfordii Hook. f. treatment induced an increase in mean luteinizing hormone, fdlicle-stimulating hormone levels and a decrease in mean estradiol, progesterone levels. CONCLUSIONS: Tripterygium wilfordii Hook. f. may be an effective therapeutic agent for leiomyomas with fewer side effects. Tripterygium wilfordii Hook. f. treatment showed a reversibly inhibitory effect on the ovary. It may be one of the mechanisms of Tripterygium wilfordii Hook. f. in decreasing leiomyoma volume. PMID- 11776195 TI - [Preliminary analysis of chromosome mosaicism in preimplantation embryos]. AB - OBJECTIVE: Using fluorescence in situ hybridization to analyze chromosome mosaicism in human preimplantation embryos and access the influence of mosaicism on in vitro fertilization-embryo transfer (IVF-ET) and preimplantation genetic diagnosis. METHODS: Normal fertilized embryos, which were not suitable for embryo transfer and cryopreservation, and male embryos in preimplantation gender diagnosis were analyzed by fluorescence in situ hybridization. RESULTS: Two hundred and ninety three nucleuses were found among 38 embryos. The hybridization rate was 96.2%. Twelve embryos (31.6%) were normal. Twenty-eight embryos (73.7%) were diploid embryos, which included normal diploid embryos and embryos with diploid moscaicism. In addition, 19 (50.0%) embryos were considered to be chromosomal mosaics due to diploid mosaicism and abnormal mosaicsm. The frequency of mosaicism increased from 18.2% in < or = 4 cell-stage embryos to 68.4% and 50.0% in 5-8 cell-stage and > or = 9 cell-stage embryos respectively. CONCLUSION: The frequency of Mosaicism increases with successive cleavage divisions. Moscaicism may be one of the important factors affecting the success rates in IVF ET. Identification of sex by analysis of a single cleavage cell is accurate; however, it would be better to biopsy 2 cells to reduce errors in preimplantation genetic diagnosis of single gene diseases. PMID- 11776196 TI - [Study on the amplification uniformity of whole genome in a single cell by degenerate oligonucleotide primed polymerase chain reaction]. AB - OBJECTIVE: To investigate the uniformity of whole genome amplification from a single cell by degenerate oligonucleotide primed polymer ase chain reaction (DOP PCR). METHODS: Amplification of the whole genomic DNA from a single cell with XX, XY, XO, XXY, +13 or +21 was performed by DOP-PCR. Comparative genomic hybridization (CGH) of a single cell DOP-PCR product against the genomic DNA or a single cell DOP-PCR product from normal male as carried out respectively. RESULTS: The average profile of fluorescence intensive ratio in CGH with the genomic DNA as the reference was greatly fluctuated and the standard deviation in about 30% haploid was beyond the normal limits. False positive hyperrepresentation was existed in X chromosome while trisomy 13 and 21 were failed to be detected. However, the distributions of the mean and the standard deviation of the ratio in the CGH with DOP-PCR product as the reference were acceptable. The copy number changes of chromosome X, Y, 13 and 21 were demonstrated. CONCLUSION: Although the single cell DOP-PCR product is not completely uniform, it would be reliable to study the whole genome of a single cell by controlling the conditions of PCR and selecting the suitable control reference because the unequal amplification is unrandom. PMID- 11776197 TI - [Preclinical study of preimplantation genetic diagnosis in animal]. AB - OBJECTIVE: To perform preimplantation genetic diagnosis (PGD) in transgenic mice. METHODS: Single blastomere from murine heterozygous pre-embryo at 4 or 8-cell stage was sampled by microbiopsy for detection of the human gene delta F508 mutation of cystic fibrosis and biopsied pre-embryo was transferred to Swiss mice foster mothers. delta F508 mutation detection on the single blastomere was performed with nested polymerase chain reaction(PCR). RESULTS: (1) Significant difference was not observed statistically for the in vitro hatching rate (n = 102), the birth rate (n = 79), birth weight and organ weight (n = 133) at 3 weeks after births between mice born from biopsied embryos and controls. (2) Thirty-two nested PCR were performed for the diagnosis of the cystic fibrosis delta F508 mutation, with 100.0% specificity and 100.0% sensitivity. CONCLUSIONS: Microbiopsy of pre-embryos with 4 or 8-cells did not alter their viability and further development. The technique of nested PCR on a single blastomere for the detection of cystic fibrosis delta F508 mutation is reliable. PMID- 11776198 TI - [Detecting embryo sex by fluorescence in-situ hybridization in preimplantation genetic diagnosis]. AB - OBJECTIVE: Applying fluorescence in situ hybridization(FISH) in preimplantation gender diagnosis. METHODS: Ovarian hyperstimulation was performed in 2 hemophilia A carriers and 2 patients with Y chromosome abnormality. Embryo sex was identified by single blastomere FISH after embryo biopsy. Female embryos were transferred into uterus. RESULTS: A total of 110 cumulus-oocyte complex were retrieved in 5 treatment cycles. Among them, 68.2% showed normal fertilized pronuclei and 55 embryos were available for embryo biopsy. The success rate of biopsy was 85.5%, with further cleavage rate of 61.7%. In FISH procedure, one cell was lost during fixation, led to 97.9% fixation rate. Totally, 18 female embryos were diagnosed and 16 were transferred into uterus. Two clinical and one biochemical pregnancies were achieved. The diagnosis was confirmed by the following analysis of aminocyte and embryonic buds after embryo reduction respectively. CONCLUSIONS: FISH is an efficient and accurate technique for determination of the sex of human preimplantation embryos. Selective abortion and birth of affected child can be avoided by preimplantation gender diagnosis. PMID- 11776199 TI - [Expression of epidermal growth factor receptor in human preimplantation embroys]. AB - OBJECTIVE: To investigate the expression of epidermal growth factor receptor (EGFR) in human preimplantation embryos and to explore the effect of EGFR on human embryos growth, development and implantation. METHODS: To detect the localization and expression of EGFR in human preimplantation embryos with indirect immunofluorescence assays(IIF). RESULTS: There was EGFR expression in human preimplantation embryos from unfertilized oocyts, 2-cell, 4-cell, 6-8 cell to 10-cell stages embryos. EGFR protein located on the cell membrance surface, and had no obvious variation in intensity of staining from whole stages embryos. CONCLUSION: The expression of EGFR was present in human preimplantation embryos, heparin-binding EGF-like epidermal growth factor (HB-EGF), one of the EGF superfamily members act through the EGFR, EGFR expression may have an important role in human embryos growth, development and implantation. PMID- 11776200 TI - [Prenatal diagnosis of fetal congestive heart failure by color flow imaging and pulse Doppler ultrasound]. AB - OBJECTIVE: To investigate prenatal diagnosis of fetal congestive heart failure (CHF) by Color Doppler Flow Imaging (CDFI) and pulse Doppler Ultrasound (PU). METHODS: 3,841 pregnant women were detected by ultrasound. Maternal-placental fetal circulation surveillance by high resolution Doppler ultrasound was performed in 302 high-risk pregnancies. The diagnosis of CHF is dependent upon (1) The cardiac area/chest area ratio > 0.33; (2) An abnormal umbilical vein pulsation; and (3) Tricuspid regurgitation. RESULTS: There were six deaths that all had abnormal umbilical vein pulsation and five cases who had C/T area ratio > 0.33. CHF accounted 0.17% in all the pregnancies and 2% in high-risk pregnancies. CONCLUSIONS: The results suggest that blood velocity recording abnormal pulsed sign in the umbilical veins and C/T area ratio of the fetus can give valuable clinical information with regard to the presence of fetal CHF. Fetus with CHF almost always had poor outcome. CDFI and PU may have implications for fetal diagnostic work-up and prognosis. PMID- 11776201 TI - [Study on normal pregnancy and recurrent spontaneous abortions from helper T cell 1/helper T cell 2 cytokines balance]. AB - OBJECTIVE: To investigate the function of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL 4, IL-10) cytokine balance in the maternal-fetal tolerance. METHODS: The IFN gamma, TNF-alpha, IL-4 and IL-10 mRNA were studied from PBMCs of 11 normal non pregnancy control, 10 women in first trimester of normal pregnancy, 11 women in last trimester of normal pregnancy by semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) method. RESULTS: (1) The IFN-gamma mRNA decreased [(24.68 +/- 5.55)%, P < 0.05], while the IL-10 mRNA rose [(20.72 +/- 5.36)%, P < 0.01] in normal pregnancy women compared with the non-pregnancy control [IFN-gamma(30.76 +/- 5.35)%, IL-10 (13.58 +/- 3.91)%]. (2) IL-10 mRNA decreased [(9.48 +/- 2.84)%, P < 0.05], while the IFN-gamma mRNA rose [(36.08 +/- 5.75)%, P < 0.05] in RSA women compared with the non-pregnancy control. (3) The IFN-gamma mRNA rose (P < 0.01), while the IL-10 mRNA decreased (P < 0.01) in RSA women compared with women in their first trimester of normal pregnancy [IFN gamma(27.23 +/- 5.74)%, IL-10 (18.61 +/- 5.43)%]. CONCLUSIONS: The results suggest that women in normal pregnancy had mainly the Th2 cytokines. The breakage of the Th1/Th2 balance may result in RSA. The results provide clue that Th1/Th2 balance plays a role in maternal-fetal tolerance. PMID- 11776202 TI - [Changes of selenium concentration in blood and placenta in intrahepatic cholestasis of pregnancy]. AB - OBJECTIVE: To explore the effect of deficiency of blood selenium and placental selenium on the damage of histomorphology of the placentas in ICP. METHODS: We measured the selenium concentration by a catalytic polorographic method in blood and placenta and glutathione peroxidase (GSH-Px) activity by a 5,5'-dithionbis (2 nitrobenzoic acid) direct method in blood in 30 women with ICP (ICP group) and 30 normal pregnant women (control group). Furthermore, the features of the placentas (10 from control group and 10 from ICP group) pathologic changes were observed microscopically. RESULTS: (1) The selenium concentrations in blood (0.0389 +/- 0.0090) mg/L and placenta (0.3770 +/- 0.0964) mg/kg and the activity of GSH-Px (59.31 +/- 11.42) U in ICP group were found to be significantly lower than those in blood (0.0477 +/- 0.0094) mg/L and placenta (0.4554 +/- 0.0626) mg/kg and the activity of GSH-Px (68.48 +/- 10.47) U in control group, respectively (P < 0.002). (2) The activity of GSH-Px had a significant positive correlation with selenium concentration in blood in ICP group (r = 0.05498, P < 0.001) and in control group (r = 0.06234, P < 0.001). There was a positive correlation between blood and placental selenium concentrations in ICP group (r = 0.6473, P < 0.001). On the other hand, there was not correlation in women with normal pregnancies. (3) Placentas obtained from women with ICP had swelling and fibrinoid necrosis of villi, increasing number of syncytial sprouts, thickening of vasculo-syncytial membrane (VSM) and decreasing size of the intervillous space under light microscopy. Placentas from control group did not show the pathologic changes as mentioned above. CONCLUSIONS: As selenium constitutes the active part of GSH-Px, these results suggest that the placental selenium deficiency may lead to reduced placental GSH-Px activity and the antioxidative defence may have been defective which may be associated with the damage of histomorphology of the placentas in ICP. PMID- 11776203 TI - [In vitro effect of danazol on cytokine production of macrophages in peritoneal fluid of infertile patients with endometriosis and its relationship with cytosolic free calicum concentration]. AB - OBJECTIVE: To investigate in vitro effect of danazol on cytokine production of macrophages in peritoneal fluid from infertile patients with endometriosis and its relationship with cytosolic free calicum ([Ca2+]i) concentration. METHODS: Pertitoneal macrophages were obtaind from 14 cases of 24 infertile women with endometriosis (EM group) and 11 cases of 19 infertile women with normal pelvis (control group). Danazol was added to peritoneal macrophages culture reaching final concentrrations of 10 micrograms/L, 100 micrograms/L, 1,000 micrograms/L respectively. Tumor necrosis factor alpha(TNF-alpha) and interleukin-6 (IL-6) levels in macrophage supernatant were detected by enzyme linked immunoassay. The [Ca2+]i of cultured peritoneal macrophage and its changes after danazol addition were also studied. RESULTS: In EM group TNF-alpha and IL-6 levels in peritoneal macrophage supernatant and [Ca2+]i of macrophages were elevated significantly as compared with those in control group. When danazol was added to the cell culture and reached 100 micrograms/L of concentration, the levels of TNF-alpha and IL-6 in cultured macrophage supernatant and the [Ca2+]i of macrophages in EM group decreased significantly (P < 0.01). CONCLUSION: It is suggested that danazol may exert its suppressive effect on endometriosis by inhibiting cytokine release of peritoneal macrophages and may related to decline of [Ca2+]i concentration. PMID- 11776204 TI - [The efficacy and safety of domestic luteinizing hormone-releasing hormone analogue and low-dose norethindrone "add-back" therapy in the treatment of endometriosis]. AB - OBJECTIVE: To study the efficacy and safety of combining domestic luteinizing hormone-releasing hormone analogue(LHRH-a) with low-dose norethindrone in the treatment of endometriosis. METHODS: Seventy-seven women with endometriosis were randomized into one of the following two groups. Group A (n = 36) were treated with LHRH-a (150 micrograms/d, i.m.) plus norethindrone (2.5 mg/d, p.o.) and group B (n = 41) received only LHRH-a (150 micrograms/d, i.m.) for 3 to 6 months. Symptoms and signs were recorded before and after the treatment. Liver and renal functions, lipid and bone metabolism and speed of sound (SOS) in the tibia were also examined at the same time. All data were analyzed using paired and grouped Student's t-tests. RESULTS: Total subjective symptom scores of group A showed 82% decrease at 3 months and 94% at 6 months of treatment (P < 0.01). Reductions in endometriotic foci were 34% and 61% at 3 and 6 months, respectively (P < 0.01). Of group B, there were 77% and 90% decreases in total subjective symptom scores at 3 and 6 months of treatment (P < 0.01). Reductions of 37% and 38% in endometriotic foci were observed at 3 and 6 months, respectively (P < 0.01). Liver and renal functions and fast blood sugar of both groups were all in normal range. Triglyceride (TG), apolipoproteinA (ApoA), serum calcium, phosphorus and alkaline phosphatase levels of group B increased significantly after treatment. And significant differences between the two groups were observed. There's no change of SOS in the tibia within or between the two groups before and after treatment. The percentages of hemorrhage in the group A and B were 18% and 38%, respectively. The percentages of hot flush and the other vasomotor symptoms were 14% and 41%, respectively (P < 0.01). CONCLUSIONS: Domestic LHRH-a combined with low-dose norethindrone was effective in the treatment of endometriosis. It could also improve the symptom of hypoestrogenemia, decrease hemorrhage rete and bone turn-over. PMID- 11776205 TI - [High-dose chemotherapy with peripheral-blood stem cells transplantation in patients with advanced gynecological malignant tumors]. AB - OBJECTIVE: To evaluate the clinical effectiveness of high dose chemotherapy(HDC) with peripheral-blood stem cells transplantation(PBSCT) in the patients with advanced malignant tumors. METHODS: Four patients with advanced or refractory ovarian carcinoma and 1 patient with recurrent fallopian tube carcinoma received the HDC with PBSCT after optimal tumor debulking. Of whom 4 patients were with the recurrent or progressive tumors, 1 patient received HDC as primary chemotherapy. The response and toxicity were assessed after treatment. RESULTS: Among 5 patients, four patients are survival. One case died from the recurrence of juvenile granulosa cell tumor. The average survival periods were 21 months. The tumors were all recurrent among the 4 survival patients. The average periods of recurrence after HDC treatment was 9 months. The main toxicity of HDC was severe marrow suppression. The lowest value of the neutrophil count and platelet count was 0.05-0.2 x 10(9)/L and 7 x 10(9)/L-8 x 10(9)/L respectively. The median time to recover a neutrophil count greater than 0.5 x 10(9)/L was 14 days and a platelet count greater than 50 x 10(9)/L was 17 days. None of the patients was complicated with severe complications. CONCLUSIONS: HDC and PBSCT used for ovarian carcinoma was flexibility and security if the patient was selected strictly though its toxicity was severe. Further study among the chemorefactory recurrent patients need to try in the future. PMID- 11776206 TI - [Surgical treatment and prognostic analysis of 39 cases invasive vulvar cancer]. AB - OBJECTIVE: To summarize the procedure of operations and evaluate the prognostic factors in the invasive vulvar cancer. METHODS: Thirty nine cases with invasive vulvar cancer admitted in our hospital from 1979 to 1997 were retrospectively analyzed. Three kinds of operations were used: 5 by local excision, 13 by modified radical vulvectomy and 21 by radical vulvectomy. Statistical package for social sciences (SPSS) was used to compare the different strategy of operation and analyze the prognostic factors. RESULTS: Thirty three patients (84.6%) had squamous cell carcinoma and 26 of them (78.8%) were well differentiated and 2 poorly differentiated. Seven cases (17.9%) were in FIGO stage I; 17 (43.6%) in stage II; 13 (33.3%) in stage III, and 2(5.1%) in stage IV, 58.3% of tumor in stage I and II were lateral while 73.3% of tumor in stage III and IV were median type. Hospitalization time for local excision, modified radical vulvectomy and radical vulvectomy (separated and en-bloc incision) were 9.1, 20.6, 41.2 and 62.2 days (P < 0.01) and the incision infection rate were 0%, 30.8%, 66.7% and 88.9% (P < 0.01) respectively. Median survival time for stage I, II, II and IV were 132.0, 121.5, 67.5 and 21.5 months (P = 0.01) and the 5-year survival rates of them were 85.7%, 70.6%, 46.2% and 0.0% (P < 0.05) respectively. Median survival time for patients with or without lymph nodes involvement were 66.0 and 121.5 months (P < 0.01) and the 5-year survival rates were 30.0% and 71.5% (P < 0.05) respectively. Median survival time for well or poor differentiation were 97.0 and 64.0 months (P > 0.05) and the 5-year survival rates were 62.0% and 43.0% (P > 0.05) respectively. CONCLUSIONS: The important prognostic factors for invasive vulvar cancer were sites(lateral/median), stage, differentiation and lymph nodes involvement. Individualized treatment should be considered. PMID- 11776207 TI - Simulation of the surface EMG of an active muscle. AB - A model of the motoneuronal (MN) pool-muscle system was developed. The model consists of four modules: (1) the input to the MN pool, (2) the MN pool, (3) the muscle and (4) the surface electromyogram (EMG). A control parameter activates the input fibers and determines the activity level of the muscle. A single compartment model with a homogenous membrane was used to model the MNs. The trajectory between spikes is determined by two voltage-gated K(+)- and two voltage-gated Ca(2+)-channels. The size of the MNs is adjusted by the size of the leakage conductance. The model muscle is of circular cross section and with parallel fibers. The motor unit (MU) territories are of circular shape and their area is proportional to the MU contraction force. Action potentials propagated along the muscle fibers are approximated by a dipole with a current source and current sink. The potential evoked by the dipole at the recording site is computed. The surface EMG is obtained by summing up (1) the potentials of all fibers of the MU and (2) the MU action potentials of all active MUs. Numerical results show that the MUs are recruited with increasing contraction force and that the active MUs modulate their firing frequency similar as in real muscles. The model will be used for investigation of the motor system in man. PMID- 11776208 TI - Neural network for sleep EEG K-complex detection. AB - The paper presents the development and application of an automatic system used to detect and classify the K-complexes aperiodic, waveforms found in electroencephalograms of patients during stage two sleep. The slow-wave transient K-complex is evoked by auditory or somatosensory stimulation being an event related potential. The analysis of this transitory waveform contributes to the assessment of sleep stages used by controlled learning during sleep. In our work we used a TMS320C30 DSP to implement an automatic detection procedure based on features extraction and classification using a feed-forward neural network. PMID- 11776209 TI - [An implantable telemetry system for impedance spectroscopy]. PMID- 11776210 TI - [Data analysis of combined eye-hand reactions for examination of motor coordination]. PMID- 11776211 TI - [A model for phase-dependent modulation of stretch reflexes by active and passive oscillatory background activity]. PMID- 11776212 TI - [Modeling and signal analysis of local myocardial arousal]. PMID- 11776213 TI - [Signal processing in functional nuclear magnetic resonance tomography (FMRI) during pain stimuli]. PMID- 11776214 TI - [Nonlinear analysis of heart rate for objective assessment of cardiac autonomic dysfunction after craniocerebral trauma]. PMID- 11776215 TI - The use of Matlab for colour fuzzy representation of multichannel EEG short time spectra. AB - During the last years, a lot of EEG research efforts was directed to intelligent methods for automatic analysis of data from multichannel EEG recordings. However, all the applications reported were focused on specific single tasks like detection of one specific "event" in the EEG signal: spikes, sleep spindles, epileptic seizures, K complexes, alpha or other rhythms or even artefacts. The aim of this paper is to present a complex system being able to perform a representation of the dynamic changes in frequency components of each EEG channel. This representation uses colours as a powerful means to show the only one frequency range chosen from the shortest epoch of signal able to be processed with the conventional "Short Time Fast Fourier Transform" (S.T.F.F.T.) method. PMID- 11776216 TI - [Event synchronous ECG artifact suppression in diaphragmatic electromyography]. PMID- 11776217 TI - [A configurable architecture for management, processing and visualizing biological signals]. PMID- 11776218 TI - [Concept for an internet-based databank for supporting projects in the area of biosignal analysis]. PMID- 11776219 TI - [Efficient creation of complex adaptive assessment algorithms by object orientated programming]. PMID- 11776220 TI - [Telemonitoring of intramyocardial electrocardiograms]. PMID- 11776221 TI - [Ilm-Map for the internet]. PMID- 11776223 TI - Analysing the spectral properties of EEG ictal events with time-frequency transform. AB - Analysis of EEG events, as e.g. the epileptic seizures, is a challenge for a lot of research that has been carried out during the last five years. New methods are required to better analyse the epileptic transients occurring during seizures. This paper discusses a model for features extraction from EEG signal to determine a specific signature of the seizure (inter-ictal) and to detect it using an artificial neural network, or just to provide a better representation of the frequency changes to the clinician. PMID- 11776222 TI - [Diagnosis-related pattern search and background classification of long-term EEG/ECoG registration in epilepsy patients]. PMID- 11776224 TI - [Object-oriented modelling for multi-channel EEG signals]. PMID- 11776225 TI - [Noninvasive determination of vascular compliance]. PMID- 11776226 TI - [GOFI--a neurofeedback system for child and adolescent psychiatry]. PMID- 11776227 TI - [ECG signal analysis by pattern comparison and ECG databanks]. PMID- 11776228 TI - [Analysis of nonuniform signals exemplified by vibration of vocal cords]. PMID- 11776229 TI - A microcontroller-based fast evoked potentials recorder. PMID- 11776230 TI - Myoelectric signal classification using neural networks. AB - A feed-forward neural network is used for diagnosis of spastic paralysis. It is a two-layer perceptron and it is able to classify two kinds of myoelectric signal recorded in surface electromyography: the normal EMG and the EMG in the case of spastic paralysis. The myoelectric signal was recorded with a surface electrode pair and sampled at 10 kHz. The EMG activity is stochastic and the instantaneous amplitude distribution for a fixed level of contraction is Gaussian. The signal variance is considered a measure of muscle force. We can describe any kind of this process by the AR model. For a precisely modeling of EMG there are necessary many AR model parameters. In the classification problem we have it is not necessary to use a high order AR model. We find a 4-th order AR model is good enough for this study. The Hopfield algorithm is used to calculate the parameters of the autoregressive model. PMID- 11776231 TI - [Computer-assisted evaluation of electromyography and goniometry signal with statistical signal analysis methods]. PMID- 11776233 TI - Untangling the Web 2. PMID- 11776234 TI - Seminars on management topics for doctors in training. PMID- 11776232 TI - Effects of a 21 days spaceflight on the mechanical performance and the EMG power spectrum of the leg muscles. PMID- 11776235 TI - Working conditions and adverse pregnancy outcomes. PMID- 11776236 TI - Effects of peer education on dietary change. PMID- 11776238 TI - Nomenclature for factors of the HLA system, update August 2001. PMID- 11776237 TI - Extrarenal potassium transport. PMID- 11776239 TI - Nomenclature for factors of the HLA system, update September 2001. PMID- 11776240 TI - [Adrenal gland diseases. Foreword]. PMID- 11776241 TI - [Otitis media in children. Foreword]. PMID- 11776242 TI - Hey doc...can we talk? PMID- 11776245 TI - [AIDSVAX, the first vaccine in phase III]. PMID- 11776244 TI - Self-assessment quiz. PMID- 11776246 TI - [Ethical elements in the development of vaccines against HIV/AIDS]. PMID- 11776247 TI - [Viral resistance tests]. PMID- 11776248 TI - [PolyEnv, a new strategy in the development of anti-HIV vaccines]. PMID- 11776249 TI - Control of hypertension. PMID- 11776250 TI - Alvan Feinstein, the father of clinical epidemiology, 1925-2001. PMID- 11776251 TI - Early detection of inhaled anthrax infection: nuclear medicine investigational nod. PMID- 11776252 TI - Medicare's new enrollment procedures for independent diagnostic testing facilities. PMID- 11776253 TI - A review of trends and demands for PET imaging: one community hospital's experience. PMID- 11776254 TI - Induction and repair of HZE induced cytogenetic damage. AB - Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time. PMID- 11776255 TI - Proposal for biochemical dosimeter for prolonged space flights. AB - Radiation dosimetry has been developed by means of physical, chemical and biological methods. A different approach to calculate the absorbed dose is related to the assay in body fluids of some molecules that modify their concentration after irradiation. The salivary glands in humans appear particularly radiosensitive and the effects of ionizing radiation can be evaluated by means of the determination of serum amylase (produced by acinar cells) and Tissue Polypeptide Antigen (TPA, synthesized by ductal cells). Patients submitted to external radiotherapy for tumours localized in the head and neck region show early and late effects on salivary glands. The modification of amylase activity and TPA appear as a progressive statistically significant increase within two days. Levels of 200-300% of baseline value are reached, followed by a rapid return to preirradiation levels. The use of different doses per fraction and fractionation schedules (conventional or multiple daily fractionations) confirm the direct correlation between the absorbed dose and serum amylase and TPA levels. It is worth noting that the irradiation of pancreas region did not produce any effect on amylase activity. The correlation may be assumed as linear for a short dose range (2-6 Gy) whereas in the range from 0.5 to 10 Gy a sigmoid curve represents the experimental data. Both molecules confirm their capability to quantify the absorbed dose in patients with thyroid carcinoma submitted to metabolic treatment with iodine-131. The effects of radiation are species-specific and are absent in laboratory mammals. The easiness of the determination of serum amylase and TPA lead us to propose the test as biochemical dosimeter for cosmic rays exposure during prolonged staying in the space. PMID- 11776256 TI - Polyamines as biochemical indicators of radiation injury. AB - The search for parameters of different nature to quantify radiation damage is carrying on from many years in humans and lab animals. The polyamines (spermidine and spermine) are ubiquitous polycations with many metabolic functions and can be easily assayed by HPLC method. Their involvement in cell proliferation has been evidenced in healthy and tumour tissues. Statistically significant reductions have been demonstrated in tissues and in red blood cells (RBC), in animals and in patients treated by total body irradiation (TBI) before bone marrow transplantation (BMT). In rats submitted to TBI with 3 Gy of gamma radiations, tissue polyamines significantly decrease during the early phase of injury in tissues with high proliferative activity (small intestine, spleen) whereas do not show any modification in kidney. When recovery takes place, the polyamines significantly increase and return to control levels when a normal morphology is restored. In patients submitted to radiation therapy, polyamines have been determined in urine and in RBC of patients with carcinoma of uterine cervix, head and neck and prostate, treated by external radiotherapy, and with thyroid cancer treated with iodine-131 therapy. The most interesting results has been obtained with RBC: in patients treated on the pelvis for prostate cancer a significant reduction during radiotherapy occurs, followed by the maintenance of low levels in patients with favourable outcome. It should be noted that polyamine levels before treatment appeared significantly higher than in healthy controls. After TBI the RBC polyamines show a dramatic fall to extremely low levels during the phase of marrow aplasia. The values show an increase corresponding to the engraftment of transplanted cells and to the following marrow repopulation. These evidences make the RBC polyamines very interesting parameters to monitor the radiation effects on humans. PMID- 11776257 TI - HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals. AB - Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals. PMID- 11776258 TI - Mutation induction by heavy-ion irradiation of gpt delta transgenic mice. AB - Using the new transgenic mice produced by mating gpt delta with p53 knockout, mutation induction by heavy-ion irradiation and the effect of p53 background on such induction were studied. After the whole body irradiation with 10 Gy of 135 MeV/u carbon-ion beam, the genomic DNA was isolated from the different organs and the lambda DNA was rescued as a phage. Mutations in the transgene on the lambda DNA were determined by the spi(-) selection (deletion assay). The spi(-) mutation was induced by the above irradiation, but enhancement of the mutant frequency by the knockout of p53 gene was found not in the phages recovered from liver but in those from kidney. We are now making an effort to determine the nature of spi(-) mutation to confirm such p53 effect. PMID- 11776259 TI - Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS). AB - Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected. PMID- 11776260 TI - Effects of exposure to 56Fe particles on the acquisition of a conditioned place preference in rats. AB - Exposure to low doses of 56Fe particles produces changes in neural function and behavior. The present experiments were designed to examine the effects of irradiation on the acquisition of a dopamine-mediated conditioned place preference (CPP). In the CPP procedure, rats are given an injection of the dopamine agonist amphetamine in one distinctive compartment and a saline injection in a different compartment of a three-compartment apparatus. Control rats develop a preference for the amphetamine-paired compartment. In contrast, rats exposed to 1 Gy of 56Fe particles fail to develop a similar preference. The results of the experiment indicate that exposure to low doses of heavy particles can disrupt the neural mechanisms that mediate the reinforcement of behavior. PMID- 11776261 TI - High-LET-induced chromosomal damage: time-dependent expression. AB - Chromosome aberrations are routinely analysed in metaphase cells at one sampling time post-irradiation. Yet, accumulating evidence shows that radiation-induced cycle perturbations and mitotic delay influence the yield of aberrations detectable in mitosis. In extended time-course studies a drastic increase in the number of aberrations with sampling time has been observed after particle irradiation, while after the exposure to sparsely ionizing radiation a less pronounced effect has been found. This difference in the time-course of chromosomal damage is particularly important for the determination of accurate RBE values. As will be discussed, meaningful RBE values for particles can only be obtained, if cells are analysed at multiple sampling times and the complete time course of aberrations is considered. Otherwise, particle-induced damage will be over- or underestimated. Moreover, depending on the cell system chosen for the analysis, factors like the loss of damaged cells due to apoptosis or a permanent cell cycle arrest complicate the determination of accurate RBE values based on chromosome data. PMID- 11776262 TI - Clustered DNA damages induced by high and low LET radiation, including heavy ions. AB - Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- ~20%, with the other clustered damages being at least 80%. PMID- 11776263 TI - Evidence for factors modulating radiation-induced G2-delay: potential application as radioprotectors. AB - Manipulation of checkpoint response to DNA damage can be developed as a means for protecting astronauts from the adverse effects of unexpected, or background exposures to ionizing radiation. To achieve this goal reagents need to be developed that protect cells from radiation injury by prolonging checkpoint response, thus promoting repair. We present evidence for a low molecular weight substance excreted by cells that dramatically increases the duration of the G2 delay. This compound is termed G2-Arrest Modulating Activity (GAMA). A rat cell line (A1-5) generated by transforming rat embryo fibroblasts with a temperature sensitive form of p53 plus H-ras demonstrates a dramatic increase in radiation resistance after exposure to low LET radiation that is not associated with an increase in the efficiency of rejoining of DNA double strand breaks. Radioresistance in this cell line correlates with a dramatic increase in the duration of the G2 arrest that is modulated by a GAMA produced by actively growing cells. The properties of GAMA suggest that it is a low molecular weight heat-stable peptide. Further characterization of this substance and elucidation of its mechanism of action may allow the development of a biological response modifier with potential applications as a radioprotector. GAMA may be useful for protecting astronauts from radiation injury as preliminary evidence suggests that it is able to modulate the response of cells exposed to heavy ion radiation, similar to that encountered in outer space. PMID- 11776264 TI - Enhanced green fluorescent protein (EGFP) for space radiation research using mammalian cells in the International Space Station. AB - In the endeavour to assess radiation risks for humans in space the concerted action of all stimuli (e.g. radiation and microgravity) has to be known already at a cellular level. The introduction of reporter genes into mammalian cells which allows the visualisation of modified gene expression levels, signal transduction rates and cell metabolism activities will supply basic information on the cellular response to space radiation. The cloning of the gene for green fluorescent protein (GFP) from the jellyfish Aequorea victoria and its subsequent expression in heterologous systems has established GFP as a unique genetic reporter system for use in a variety of organisms. Unlike other reporters, GFP fluorescence emerges in the absence of substrates or cofactors and allows for non invasive monitoring in living and in paraformaldehyde-fixed cells. Enhancement of wild-type GFP by human codon optimisation and fluorophore mutation (EGFP) resulted in higher expression levels in mammalian cells and brighter fluorescence. The suitability of EGFP for gene expression studies to be performed on the ISS is shown for recombinant mammalian cells in response to UVC exposure. PMID- 11776265 TI - Classification issues in catatonia. AB - Kahlbaum described catatonia as a disorder in which mood syndromes were the primary features and the characteristic symptoms were the motor signs. In the present study, we examined the relationship between motor features and other syndromes of psychosis, the clinical validity of Kahlbaum's concept of catatonia, its relationship to schizophrenia and mood disorder, and its nosological position in relation to DSM-III-R, DSM-IV and Leonhard's classification of endogenous psychoses. Patients with Kahlbaum's catatonia differed from patients with schizophrenia or mood disorder in various demographic and clinical variables. Positive and negative motor syndromes, although interrelated, showed a different correlational pattern with other psychotic syndromes. Catatonia did not appear to fit into any particular nosological category, although this issue largely depends on whether schizophrenia and mood disorders are broadly or restrictively defined. When definitions are more restrictive as in Leonhard's system, catatonia seems to be better accommodated as a "third psychosis", i.e. described by the concept of cycloid psychosis. PMID- 11776266 TI - Catatonic schizophrenia in Croatia. AB - A representative sample of schizophrenic subjects was collected for epidemiological and clinical follow-up in 1972 from the pool of 8069 patients registered in the Croatian Psychotics Case Register (CPCR). This sample comprised 402 patients (207 males and 195 females), who were followed up until 1990/91. The diagnosis of schizophrenia, catatonic type according to ICD-8 (V/295.2), was made in 59 cases (14.7%; 28 males, 31 females) at least once in the course of the follow-up. This study presents data concerning the diagnostic instability of the catatonic subtype during the long-term follow-up. As subtype diagnoses were frequently changed over the course of illness, at the end of the follow-up, the diagnosis of catatonic schizophrenia was only confirmed in 11 (18.6%) cases. Positive family history of psychosis was found in 44.1% of catatonic patients, a percent significantly greater than the corresponding figure for all non-catatonic schizophrenic subtypes combined (20.1%). This study provides preliminary evidence that the catatonic subtype of schizophrenia is a separate diagnostic entity with a high familial loading. PMID- 11776267 TI - Genetic predisposition and environmental causes in periodic and systematic catatonia. AB - The nosological heterogeneity of catatonic schizophrenia was the focus of a family study involving 139 catatonic patients. The clinical dichotomization of catatonia into periodic catatonia and systematic catatonia revealed good inter rater reliability and stability of the diagnoses at follow-up. Analysis of the cumulative morbidity risk among first-degree relatives gave an excessive familial aggregation of homogenous psychoses in periodic catatonia with a risk of 26.9%. The mode of inheritance was consistent with an autosomal dominant model. In contrast, first-degree relatives of probands with systematic catatonia had a morbidity risk of 4.6%. Subsequent investigations pointed to a potential association of systematic catatonia to exposure to midgestational infections in the index cases and linked these sporadic disorders to disturbances of fetal neurodevelopment. The periodic catatonia, an unequivocally genetically transmitted illness, is at present under investigation in a genome-wide linkage analysis. PMID- 11776268 TI - Towards the genetic basis of periodic catatonia: pedigree sample for genome scan I and II. AB - In a genome-wide linkage study, we mapped two major susceptibility loci for periodic catatonia, a phenotype with qualitative disturbances of the psychomotor sphere and a morbidity risk of 26.9% in first-degree relatives of index cases, to chromosome 15q15, and to chromosome 22q13 using nonparametric as well as parametric (autosomal dominant model) analyses. The study included 12 multiplex pedigrees with 135 individuals, among them 57 affected persons. A second genome scan is in progress investigating four families with 21 affected individuals, aiming to confirm linkage results. Age at onset patterns as well as the clinical outcome were similar among affected individuals in both sets of families. Within the pedigrees we observed no physical diseases segregating with periodic catatonia. Under the assumption of genetic homogeneity, the statistical power to detect LOD scores > or = 2.0 was 98.5% in the first set of families, and 57.9% in the second set. Thus, the panel of multiplex pedigrees segregating periodic catatonia seems to represent a homogenous clinical sample, and possesses sufficient statistical power to delineate and confirm linkage to major genetic loci for periodic catatonia. PMID- 11776269 TI - The pharmacological treatment of catatonia: an overview. AB - Over the past two decades, catatonia, particularly its acutely emerging akinetic hypokinetic (stuporous) variant, has gradually regained its importance in descriptive psychopathology. Electroconvulsive therapy and lately benzodiazepines are not only effective treatment options in this form of catatonia, but also helped generate neurobiological hypotheses concerning its pathophysiology. Within this broad framework, this paper summarizes the results of recent benzodiazepine treatment response studies in catatonic movement disorders with particular reference to the authors' own studies in Chinese patients with catatonia. PMID- 11776270 TI - The different conceptions of catatonia: historical overview and critical discussion. AB - The present article outlines the different conception of catatonia from its initial description by Kahlbaum to current viewpoints. Originally considered to be an independent disease entity characterized by mental and motor abnormalities, catatonia was later viewed as a subtype of schizophrenia as it is the case in current classifications like ICD-10 and DSM-IV. Since catatonic symptoms were observable not only in schizophrenic psychoses, but also in affective, somatic or even psychogenic disorders, many researchers today consider catatonia as a nosologically unspecific syndrome. In the end, the traditional conceptions did not succeed in defining catatonia as a clinically homogeneous and valid diagnosis. An independent conception was elaborated by the Wernicke-Kleist Leonhard school of psychiatry. Based on a precise differentiation of psychomotor disturbances, two essentially different forms of catatonic psychoses have been separated, systematic and periodic catatonias which differ in symptomatology, prognosis and treatment. PMID- 11776271 TI - The many varieties of catatonia. AB - About 10% of patients with severe acute psychiatric illness exhibit a cluster of motor signs (mutism, negativism, rigidity, posturing, stereotypy, staring, etc.) that are identified as the syndrome of catatonia. Catatonia responds to sedative anticonvulsant treatment (barbiturates, benzodiazepines) and to electroconvulsive therapy. These treatments raise seizure thresholds. The commonality in response indicates that catatonia, malignant catatonia, neuroleptic malignant syndrome, toxic serotonin syndrome, delirious mania, catatonic excitement, benign stupor, and oneirophrenia are best evaluated as diverse manifestations of one syndrome for clinical and neuroscience research purposes. PMID- 11776272 TI - [Alcaloids discovery, markers for the history of organic chemistry]. AB - The development of organic chemistry is well fitted by the history of dyes. Are alkaloids as good markers? In 1876, Chevreul distinguished two steps in the history of these organic alkalis. The first began with Derosne who analyzed opium in 1803, followed by Seguin and mainly Sertuerner. It was closed about 1820 with Pelletier and Caventou researches, including works of Robiquet and Gomes from Lisbon. Next years, chemists investigated properties and chemical structures. With Pasteur, alkaloids participated to the emergence of stereochemistry, and with Claude Bernard, to the birth of a new science, physiology. Chevreul could not anticipate success of organic synthesis which blooms during the XXth century. PMID- 11776273 TI - [The Boulduc dynasty, apothecaries in Paris in XVIIth and XVIIIth centuries]. AB - The Parisian Boulduc family had four apothecaries among its members from the XVIIth to the XVIIIth centuries : Pierre, Simon, Gilles-Francois and Jean Francois. Two of them were members of the Academie royale des sciences but all held important offices in the Parisian apothecary Community or in the Royal apothecaries Society. One of Pierre's five sons, Simon, was a member of the Academie royale des sciences, one other, Louis, went to Canada and became King of France Public Prosecutor at the Quebec Provostship. He got married there and his eight children were probably at the foundation of the Bolduc dynasty (they modified their name) living in Quebec. Victim of intrigues and accused of embezzlements Louis came back to France where he died. Simon's son, Gilles Francois, was like his father a member of the Academie royale des sciences and his own son Jean-Francois was the King's first apothecary. Simon Boulduc's main scientific work is presented in this first article. PMID- 11776274 TI - [The manuscript OMNIA of Charles-Louis Cadet de Gassicourt]. AB - In 16 handwritten pages, included in a booklet of large size (32 x 22 cm), Charles-Louis Cadet de Gassicourt describes some events of his life, and his thoughts which are often against the society, the Kings, the religions and also the women. This paper was written at the end of his life, probably just before 1820. PMID- 11776275 TI - Treating anemia in patients with cancer. PMID- 11776276 TI - Tumor suppressor p53 response is blunted by low-dose radiation. AB - To estimate the effects of space radiation on health of space crews, we aimed to clarify whether g-ray-irradiation at a low-dose-rate interferes in a p53 centered signal transduction pathway induced by radiation in human cultured cells and CB 17 Icr+/+ mice. In vitro experiments, the human cultured squamous cell carcinoma cells (SAS/neo) were examined for cellular levels of p53 and Bax, and the incidence of apoptosis after irradiation at a low-dose-rate (1 mGy/min) or a high dose-rate (1 Gy/min). It was found that challenging irradiation-induced apoptosis was depressed by chronic irradiation at 1.5 Gy for 25 h with the depression of p53 and Bax accumulation. In vivo experiments, a significant suppression of Bax and apoptosis induced by challenging irradiation at 3.0 Gy was observed when the mice were pre-irradiated chronically at 1.5 Gy for 25 h in the spleen of CB-17 Icr+/+ mice. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signaling and/or p53 stability. PMID- 11776277 TI - Heavy ion production of single- and double-strand breaks in plasmid DNA in aqueous solution. AB - Preliminary measurements on the production of single- and double-strand breaks in SV40 and phi X174 plasmid DNA by various heavy ions in radioprotective Tris buffer are presented. The dependence of the recorded yields on the LET of the incoming ions is discussed and shown to be comprehensible within the framework of a model based on the X-ray sensitivity of the exposed DNA and the local dose distribution inside the heavy ion track. The question of the influence of the chemical environment is addressed by comparing the measured cross sections to data recorded previously in more radiosensitive TE buffer. The results indicate that also for systems with high scavenging capacity RBE values larger than unity can be achieved with maximum values in the LET range 100-1000 keV micrometers-1. PMID- 11776278 TI - Medical devices; reclassification of three anesthesiology preamendments class III devices into class II. Final rule. AB - The Food and Drug Administration (FDA) is reclassifying three anesthesiology preamendments devices from class III (premarket approval) into class II (special controls). FDA is also identifying the special controls that the agency believes will reasonably ensure the safety and effectiveness of the devices. This reclassification is being undertaken on the agency's own initiative based on new information under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Safe Medical Devices Act of 1990 and the FDA Modernization Act of 1997. PMID- 11776279 TI - Medical devices; exemptions from premarket notification; class II devices. Final rule. AB - The Food and Drug Administration (FDA) is publishing a final rule exempting from the premarket notification requirements the fluoroscopic compression device, a manual compression device that allows a radiologist to press on the abdomen during a fluoroscopic procedure without exposing his or her hand to the x-ray beam. The device is classified as an accessory to the image-intensified fluoroscopic x-ray system. FDA received a petition requesting an exemption for the F-Spoon device, a type of fluoroscopic manual compression device. FDA is expanding the exemption for this type of generic device to include other fluoroscopic compression devices. FDA is publishing this order in accordance with the Food and Drug Administration Modernization Act of 1997 (FDAMA). PMID- 11776280 TI - Anakinra: interleukin-1 receptor antagonist therapy for rheumatoid arthritis. AB - (1) Anakinra is an interleukin-1 receptor antagonist (IL-1ra), which blocks interleukin-1 (IL-1), a protein involved in the inflammation and the joint destruction associated with rheumatoid arthritis (RA). (2) The manufacturer's submission for drug approval is currently under review by Health Canada and the FDA. (3) In randomized controlled trials, patients with severe RA were treated with anakinra. Significant improvement was demonstrated in several clinical, radiologic and health-related quality of life measures in patients treated with anakinra versus placebo. (4) Minimal adverse effects, mainly injection site reactions, were reported. PMID- 11776281 TI - Transdermally-delivered oxybutynin (Oxytrol(R) for overactive bladder. AB - (1) The oxybutynin patch is a transdermal delivery system, which releases the drug oxybutynin through the skin for the management of overactive bladder. (2) Limited evidence suggests that transdermal delivery of oxybutynin over a short period of time may have efficacy comparable to oral oxybutynin. (3) Recent phase II and III clinical trials supported by the manufacturer suggest a potentially reduced incidence of dry mouth compared to oral oxybutynin. Itching, however, is present in 18% of patients, and the patients' withdrawal rate due to adverse events after 12 weeks is significant (10%). (4) More studies are required to determine the long-term efficacy and safety of the oxybutynin patch for overactive bladder. (5) A New Drug Application for transdermal oxybutynin (Oxytrol(R)) is currently under review at the U.S. Food and Drug Administration. As of October 2001, the oxybutynin patch has not been approved in Canada. PMID- 11776282 TI - Antidrug and alcohol misuse prevention programs for personnel engaged in specified aviation activities. Final rule; technical amendment. AB - The FAA is making minor technical amendments to its drug and alcohol regulations final rule, which was effective August 1, 2001. Since publication of the final rule, we have become aware of minor corrections that need to be made to avoid confusion. The effect of this technical amendment will be to correct the rule language to reflect the intent of the final rule. PMID- 11776283 TI - Revised medical criteria for determination of disability, musculoskeletal system and related criteria. Final rules with request for comments. AB - We are revising the criteria in the Listing of Impairments (the listings) that we use to evaluate musculoskeletal impairments in adults and children who claim Social Security or Supplemental Security Income (SSI) benefits based on disability under titles II and XVI of the Social Security Act (the Act). There visions reflect advances in medical knowledge, treatment, and methods of evaluating musculoskeletal impairments. When the final rules become effective, we will apply them to new applications filed on or after the effective date of the rules and to other claims described in the preamble. Individuals who currently receive benefits will not lose eligibility as a result of these final rules. Also, although some individuals with musculoskeletal impairments will not meet the requirements of these final listings, they may still be found disabled at a later step in the sequential evaluation process based on their functional limitations. PMID- 11776284 TI - Inhaled insulin for the treatment of diabetes mellitus. AB - (1) Insulin delivery via inhalation, as an alternative to administration by injection, is under development. (2) The available evidence comparing subcutaneous (sc) insulin with inhaled insulin for persons with type 1 and 2 diabetes, shows similar glycosylated hemoglobin (HgA1c) levels after three months of treatment. (3) Clinical trials suggest that insulin delivered by inhalation has a quicker onset of action relative to regular insulin. This means insulin can be taken just prior to a meal rather than the 30 minutes prior to eating required with sc injections of regular insulin. (4) No changes in pulmonary function were noted in the studies, however data is limited to use for three months. Pulmonary thrombosis has subsequently been reported in one patient out of 1000, using Exubera(R) and the Inhale Therapeutic Systems device. PMID- 11776285 TI - Omapatrilat for the management of heart failure and hypertension. AB - (1) Omapatrilat, first in a new class of cardiovascular drugs called vasopeptidase inhibitors, is under evaluation for the management of hypertension and heart failure. (2) Several small trials have demonstrated the efficacy and tolerability of once-daily omapatrilat in the treatment of mild to moderate hypertension. Efficacy data from one medium-sized trial have demonstrated a benefit comparable to lisinopril in the treatment of systolic heart failure. (2) The benefits and risks of omapatrilat as compared to ACE inhibitors are under evaluation and could affect future clinical therapy guidelines for managing hypertension and heart failure. PMID- 11776286 TI - Rosuvastatin: do we need another statin? AB - (1) Rosuvastatin (Crestor(TM)) is a new synthetic agent for the treatment and prevention of lipid disorders, a risk factor for coronary heart disease. (2) Rosuvastatin is undergoing phase III clinical trials. A New Drug Application was submitted to the U.S. Food and Drug Administration in June, 2001. No information on the regulatory status in Canada is currently available. (3) Limited evidence from small clinical trials suggests that rosuvastatin may produce larger dose dependent decreases in total cholesterol levels and low-density lipoprotein cholesterol levels in hypercholesterolemic patients compared to other statins. There is insufficient evidence to draw conclusions about the safety of rosuvastatin. (4) The impact of rosuvastatin therapy on cardiac morbidity and mortality is not known. More experience is required to determine the effectiveness and relative benefits of this new drug. PMID- 11776287 TI - Oxygen carriers ("blood substitutes"). AB - (1) A number of oxygen carriers, or "blood substitutes", are undergoing clinical trials. One product (Hemopure(R)) was recently licensed for use in South Africa. Another, (Hemolink(tm) may soon be approved for marketing in Canada. (2) Most trials of oxygen carriers have focused on their use in surgery, primarily as a way to minimize the need for allogeneic blood transfusion. (3) The benefits of these products in comparison with other blood conservation technologies and with allogeneic blood transfusion must be determined. (4) The safety and cost effectiveness of these products, and the patient populations that would benefit most from their use require further study. PMID- 11776288 TI - Tacrolimus ointment for the treatment of atopic dermatitis. AB - (1) Atopic dermatitis (AD) is a chronic dermatological condition characterized by pruritus (itchiness) and rash. Topical corticosteroids are the mainstay of pharmacotherapy. (2) Tacrolimus ointment is a new topical anti-inflammatory agent available in Canada through the Special Access Program. (3) It is approved as a second line agent for short or long term intermittent treatment of moderate to severe AD. (4) Clinical trials suggest it is both effective and safe, but comparative studies with corticosteroids and long-term information are limited. PMID- 11776289 TI - Foreign establishment registration and listing. Final rule. AB - The Food and Drug Administration (FDA) is issuing a final rule to amend its regulations pertaining to the registration of foreign establishments and the listing of human drugs, animal drugs, biological products, and devices. The final rule requires foreign establishments whose products are imported or offered for import into the United States to register with FDA and to identify a United States agent. The final rule implements section 417 of the Food and Drug Administration Modernization Act of 1997 (FDAMA) as it pertains to foreign establishment registration. PMID- 11776290 TI - CoMFA and CoMSIA 3D-quantitative structure-activity relationship model on benzodiazepine derivatives, inhibitors of phosphodiesterase IV. AB - Recently, we reported structurally novel PDE4 inhibitors based on 1,4 benzodiazepine derivatives. The main interest in developing bezodiazepine-based PDE4 inhibitors is in their lack of adverse effects of emesis with respect to rolipram-like compounds. A large effort has thus been made toward the structural optimization of this series. In the absence of structural information on the inhibitor binding mode into the PDE4 active site, 2D-QSAR (H-QSAR) and two 3D QSAR (CoMFA and CoMSIA) methods were applied to improve our understanding of the molecular mechanism controlling the PDE4 affinity of the benzodiazepine derivatives. As expected, the CoMSIA 3D contour maps have provided more information on the benzodiazepine interaction mode with the PDE4 active site whereas CoMFA has built the best tool for activity prediction. The 2D pharmacophoric model derived from CoMSIA fields is consistent with the crystal structure of the PDE4 active site reported recently. The combination of the 2D and 3D-QSAR models was used not only to predict new compounds from the structural optimization process, but also to screen a large library of bezodiazepine derivatives. PMID- 11776291 TI - Free energy force field (FEFF) 3D-QSAR analysis of a set of Plasmodium falciparum dihydrofolate reductase inhibitors. AB - Free energy force field (FEFF) 3D-QSAR analysis was used to construct ligand receptor binding models for a set of 18 structurally diverse antifolates including pyrimethamine, cycloguanil, methotrexate, aminopterin and trimethoprim, and 13 pyrrolo[2,3-d]pyrimidines. The molecular target ('receptor') used was a 3D homology model of a specific mutant type of Plasmodium falciparum (Pf) dihydrofolate reductase (DHFR). The dependent variable of the 3D-QSAR models is the IC50 inhibition constant for the specific mutant type of PfDHFR. The independent variables of the 3D-QSAR models (the descriptors) are scaled energy terms of a modified first-generation AMBER force field combined with a hydration shell aqueous solvation model and a collection of 2D-QSAR descriptors often used in QSAR studies. Multiple temperature molecular dynamics simulation (MDS) and the genetic function approximation (GFA) were employed using partial least square (PLS) and multidimensional linear regressions as the fitting functions to develop FEFF 3D-QSAR models for the binding process. The significant FEFF energy terms in the best 3D-QSAR models include energy contributions of the direct ligand receptor interaction. Some changes in conformational energy terms of the ligand due to binding to the enzyme are also found to be important descriptors. The FEFF 3D-QSAR models indicate some structural features perhaps relevant to the mechanism of resistance of the PfDHFR to current antimalarials. The FEFF 3D-QSAR models are also compared to receptor-independent (RI) 4D-QSAR models developed in an earlier study and subsequently refined using recently developed generalized alignment rules. PMID- 11776292 TI - Matching organic libraries with protein-substructures. AB - We present a general approach which allows automatic identification of sub structures in proteins that resemble given three-dimensional templates. This paper documents its success with non-peptide templates such as beta-turn mimetics. We considered well-tested turn-mimetics such as the bicyclic turned dipeptide (BTD), spiro lactam (Spiro) and the 2,5-disubstituded tetrahydrofuran (THF), a new furan-derivative which was recently developed and characterized. The detected geometric similarity between the templates and the protein patches corresponds to r.m.s.-values of 0.3 A for more than 80% of the constituting atoms, which is typical for active site comparisons of homologous proteins. This fast automatic procedure might be of biomedical value for finding special mimicking leads for particular protein sub-structures as well as for template assembled synthetic protein (TASP) design. PMID- 11776293 TI - Electrostatic and structural similarity of classical and non-classical lactam compounds. AB - Various electrostatic and structural parameters for a series of classical and non classical beta-lactams were determined and compared in order to ascertain whether some specific beta-lactams possess antibacterial or beta-lactamase inhibitory properties. The electrostatic parameters obtained, based on the Distributed Multipole Analysis (DMA) of high-quality wavefunctions for the studied structures, suggest that some non-classical beta-lactams effectively inhibit the action of beta-lactamases. As shown in this work, such electrostatic parameters provide much more reliable information about the antibacterial and inhibitory properties of beta-lactams than do structural parameters. PMID- 11776294 TI - Calculating the knowledge-based similarity of functional groups using crystallographic data. AB - A knowledge-based method for calculating the similarity of functional groups is described and validated. The method is based on experimental information derived from small molecule crystal structures. These data are used in the form of scatterplots that show the likelihood of a non-bonded interaction being formed between functional group A (the 'central group') and functional group B (the 'contact group' or 'probe'). The scatterplots are converted into three dimensional maps that show the propensity of the probe at different positions around the central group. Here we describe how to calculate the similarity of a pair of central groups based on these maps. The similarity method is validated using bioisosteric functional group pairs identified in the Bioster database and Relibase. The Bioster database is a critical compilation of thousands of bioisosteric molecule pairs, including drugs, enzyme inhibitors and agrochemicals. Relibase is an object-oriented database containing structural data about protein-ligand interactions. The distributions of the similarities of the bioisosteric functional group pairs are compared with similarities for all the possible pairs in IsoStar, and are found to be significantly different. Enrichment factors are also calculated showing the similarity method is statistically significantly better than random in predicting bioisosteric functional group pairs. PMID- 11776295 TI - Neuronal nicotinic receptor agonists: a multi-approach development of the pharmacophore. AB - Based on the results obtained with different automated computational approaches as applied to the study of eleven high-affinity agonists of the neuronal nicotine acetylcholine receptor (nAChR), belonging to different chemical classes, new relevant features were detected which complement the existing pharmacophores. Convergent results from DISCO (Distance Comparison), QXP (Quick Explore), Catalyst/HipHop, and MIPSIM (Molecular Interaction Potential Similarity) allowed us to identify and locate, in a well defined spatial arrangement, three geometrically independent key structural features: (i) a positively charged nitrogen atom for ionic or hydrogen bond interactions, (ii) a lone pair of the pyridine nitrogen or a specific lone pair of a carbonyl oxygen, as a hydrogen bond acceptor, and (iii) a centre of a hydrophobic area generally occupied by aliphatic cycles. The pharmacophore presented herein, along with predictive 2D and 3D QSAR models recently developed in our group, could represent valuable computational tools for the design of new nAChR agonists having therapeutical potential. PMID- 11776296 TI - Co-stimulation blockade, hemophilic inhibitors and tolerance. PMID- 11776297 TI - Blockade of CD40/CD40 ligand interactions prevents induction of factor VIII inhibitors in hemophilic mice but does not induce lasting immune tolerance. AB - Patients with severe hemophilia A frequently develop neutralizing anti-factor VIII antibodies after replacement therapy with factor VIII (FVIII). In a search for new strategies to induce immune tolerance against FVIII in these patients, we used a murine model of hemophilia A to investigate the importance of CD40/CD40 ligand (CD40L) interactions for the initiation of the anti-FVIII immune response. We focused our attention in particular on the induction of neutralizing anti FVIII antibodies and the Th1/Th2 polarization of FVIII-specific T cells. The development of anti-FVIII antibodies was analyzed by ELISA systems (detection of total anti-FVIII antibodies) and Bethesda assays (determination of neutralizing anti-FVIII antibodies). Factor VIII-specific T cells were characterized by multiparameter flow cytometry and cytokine ELISAs for the detection of cytokine production in splenic CD4+ T cells after in vitro restimulation with FVIII. Hemophilic mice received four doses of FVIII and anti-CD40L antibody MR1 (24 h before FVIII). Subsequently mice received four doses of FVIII only. The induction of neutralizing anti-FVIII antibodies in hemophilic mice after treatment with human FVIII could be prevented completely by a blockade of CD40/CD40L interactions using MR1. Furthermore, FVIII-specific T-cell responses that included both Th1 and Th2 cells were suppressed when mice were treated with FVIII and MR1. The initial blockade of CD40/CD40L interactions was, however, not sufficient to induce a lasting immune tolerance against FVIII. The immune suppression was abolished and both neutralizing anti-FVIII antibodies and FVIII specific T cells developed when treatment with FVIII was continued after the omission of MR1. In addition, there were no alterations in the Th1/Th2 polarization induced by the initial blockade of CD40/CD40L interactions. PMID- 11776298 TI - The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling? AB - Tissue factor, a 47 kDa membrane glycoprotein, lies at the basis of the extrinsic pathway of the coagulation cascade. Interaction of TF with factor VIIa results in the formation of fibrin from fibrinogen, thereby inducing the formation of a blood clot. In addition to this well-established role in blood coagulation, TF is associated with various other physiological processes such as sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. The molecular basis of the latter events is slowly emerging. It has become clear that TF-FVIIa interaction elicits a variety of intracellular signalling events that may be implicated in these actions. These events include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. How this progress in the understanding of TF associated signal transduction may generate answers as to the mechanism through which TF exerts it pleiotropic effects will be focus of this review. PMID- 11776299 TI - Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia. AB - BACKGROUND: The endothelial cell protein C receptor (EPCR) enhances protein C activation by the thrombin-thrombomodulin complex. As evidence is accumulating that EPCR is an important component of the protein C anticoagulant pathway, polymorphisms in the EPCR gene might be candidate risk factors predisposing to venous thromboembolism (VTE). Recently, a 23bp insertion in exon 3 of the EPCR gene has been identified, which duplicates the preceding 23 bases and results in a STOP codon downstream from the insertion point. However, the clinical significance of this mutation in VTE remains to be clarified. METHODS AND RESULTS: In this study we evaluated the EPCR 23bp insertion in 889 patients with documented VTE and in 500 healthy controls. The prevalence of the EPCR insertion among patients was 0.1%, which was not significantly different compared to controls (0.6%, p = 0.1). CONCLUSIONS: Our findings showed that the EPCR 23bp insertion is very rare in both patients with VTE and the general population and failed to support an association between the EPCR 23bp insertion and an increased risk of VTE. PMID- 11776300 TI - Endothelial perturbation in cystic fibrosis. AB - Cystic fibrosis (CF) is characterized by a persistent inflammatory state, which can be secondary to chronic pulmonary infection and may affect vascular endothelium. We measured circulating levels of von Willebrand factor (vWF), tissue-plasminogen activator (t-PA), and P-selectin in 20 CF patients and 20 healthy subjects. vWF, t-PA and P-selectin levels were significantly higher in CF patients. Endothelial perturbation (>2 SD increase in both vWF and t-PA) was present in 65% of CF patients. These patients displayed lower FEV1 values compared to individuals without endothelial perturbation and an inverse correlation between FEV1 and P-selectin levels was observed. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels were also increased in CF patients and significant direct correlations were found between TNF-alpha and vWF, t-PA or P-selectin levels. These results indicate that CF patients exhibit signs of endothelial dysfunction/perturbation, which are likely to be related to a persistent inflammatory state due to chronic pulmonary infection, and may play a role in the progression of this disease. PMID- 11776301 TI - Low level of circulating activated protein C is a risk factor for venous thromboembolism. AB - The levels of circulating activated protein C (APC) reflect in vivo protein C activation. The aim of this study was to determine whether a low APC level is an independent risk factor for venous thromboembolism (VTE). We measured APC in 160 patients with a history of VTE and without recognized thrombophilic defects, and in 199 healthy individuals. The mean (+/- SD) APC level was lower in patients (0.99 +/- 0.44 ng/ml) than in controls (1.19 +/- 0.41 ng/ml) (p < 0.0001), and showed a different distribution in the two groups. Thirty-eight patients (23.7%) had APC levels below the 5th percentile of the control group (<0.69 ng/ml) and 57 patients (35.6%) had APC levels below the 10th percentile (<0.77 ng/ml). APC levels <0.69 ng/ml increased the risk of a single or recurrent episode of VTE 4.2 fold (95% confidence interval, 2.0-9.0) or 6.9-fold (2.6-17.9). respectively, and APC levels <0.77 ng/ml increased these risks 3.4-fold (1.9-6.2) or 5.1-fold (2.3 11.2), respectively, compared with controls. Familial studies revealed that in some cases the low APC phenotype seems to be hereditary. We conclude that a low level of circulating APC in individuals without any of the most recognized thrombophilic defects is a prevalent, independent risk factor for VTE, and that it predisposes to recurrent VTE. PMID- 11776302 TI - Thromboprophylaxis following caesarean section--a comparison of the antithrombotic properties of three low molecular weight heparins--dalteparin, enoxaparin and tinzaparin. AB - Pharmacological thromboprophylaxis is increasingly being used after caesarean section to prevent venous thromboembolism. Although a variety of low molecular weight heparins (LMWH) have been used no comparative study exists on their effects on the haemostatic system in this situation. Furthermore, their antithrombotic effect may be mediated through effects other than their inhibitory effect on activated factor X. We compared the plasma anti-factor Xa activity, plasma concentration of tissue factor pathway inhibitor (TFPI) and the reduction in plasma thrombin-antithrombin (TAT) complex concentration in 30 women randomised to receive either dalteparin 5,000 IU anti-Xa once daily (n = 10), enoxaparin 4,000 IU anti-Xa once daily (n = 10) or tinzaparin 50 IU/kg anti-Xa (average dose 3,650 anti-Xa units) once daily (n = 10) following caesarean section. Sampling occurred at 0, 1, 3, 6, 12 and 24 h relative to time of dosing. All preparations produced an increase in mean anti-Xa assay (p < 0.0001), a reduction in mean TAT (p < 0.05) and an increase in mean TFPI concentration (p <0.05). Analysis of variance (ANOVA) revealed a significant difference between the LMWHs in terms of mean anti-factor Xa activity (p < 0.005) and reduction in plasma TAT concentration (p < 0.005). Post hoc analysis indicated that the anti Xa values of the groups receiving enoxaparin and dalteparin were significantly higher than those of the group receiving tinzaparin (p < 0.05), but not significantly different from each other. Post hoc analysis of the reduction in plasma TAT concentration showed the reduction to be significantly less in the group receiving enoxaparin compared to the dalteparin and tinzaparin groups (p < 0.05), which did not differ significantly from each other. There was no significant difference between treatment groups with regard to plasma concentration of TFPI. These findings demonstrate that LMWHs differ in their effects on haemostatic parameters including thrombin generation as assessed by TAT. The increase in TFPI may be an additional mediator of LMWH's antithrombotic effects. Although these findings demonstrate that LMWHs differ in their haemostatic effects, this does not necessarily infer a clinical difference between these agents. PMID- 11776303 TI - Low molecular weight heparin and warfarin in the treatment of patients with antiphospholipid syndrome during pregnancy. AB - Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients. PMID- 11776304 TI - Compound heterozygosity of the GPIbalpha gene associated with Bernard-Soulier syndrome. AB - We report the molecular genetic analysis of the Bernard-Soulier syndrome (BSS) phenotype in two related patients showing absence of glycoprotein (GP) Ibalpha and detectable amounts of GPIX on the platelet surface, and a truncated form of GPIbalpha in solubilized platelets and plasma. They both were compound heterozygotes for the GPIbalpha gene: a maternal allele with a T insertion at position 1418 causing a translational frameshift and premature polypeptide termination, and a paternal allele with a T715A substitution chan-ino Cys209 to Ser. Heterozygotes for either one of these mutations were asymptomatic. Transient transfection of cells coexpressing GPIbbeta and GPIX failed to detect surface expression of the GPIbalpha mutants. Cells transfected with [1418insT]GPIbalpha cDNA showed a truncated protein of the predicted size in both cell lysate and conditioned medium, indicating the inability of the mutant protein to anchor the plasma membrane. In contrast. transfection of [T715A]GPIbalpha-cDNA yield a mutated protein barely detectable in the cell lysate and absent in the medium, indicating that the loss of Cys209 renders GPIbalpha more vulnerable to proteolysis and unable to undergo the normal secretory pathway. Our findings indicate that the additive effects of both mutations are responsible for the BSS phenotype of the patients. PMID- 11776305 TI - Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families. AB - Heterozygozity for four novel missense mutations (W108C, W342R. E349K and L485S) and one novel 4 bp deletion (ACdelAAAG affecting codons 632-633) was identified in PROS1 of unrelated thrombosis prone Danish families with protein S type I or III deficiency. The 4 bp deletion results in a frameshift leading to replacement of the coding sequence for the 3 C-terminal amino acids by an abnormal extended sequence that codes for 9 amino acids. The E349K substitution was found in 7 families. Haplotype analysis using 7 microsatellite markers flanking PROS1 was consistent with a common founder for this mutation. The mutations reported here are most likely the cause of the protein S deficiency. Firstly, the four missense mutations cosegregate with the abnormal plasma protein S phenotype and lead to the loss of highly conserved amino acids. Secondly, computer analysis of structural models of protein S predicts that the substitutions could affect proper protein folding and/or stability. Analysis of platelet mRNA from subjects with the W108C, E349K, L485S mutation or the 4 bp deletion showed that mutated mRNA was expressed in significant amounts suggesting that mutated molecules are synthesized. Our results are compatible with defective protein folding/unstable molecules, impaired secretion and intracellular degradation of mutated protein, which appear to be the major molecular disease mechanisms for missense mutations and certain other mutations found in genetic disorders. PMID- 11776306 TI - Complexes between activated protein C and protein C inhibitor measured with a new method: comparison of performance with other markers of hypercoagulability in the diagnosis of deep vein thrombosis. AB - A first clinical evaluation has been made of the performance of a newly devised immunofluorometric assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI). The method was compared with testing for other markers of hypercoagulability in a case-control study comprising 123 patients with clinical suspicion of deep vein thrombosis (DVT). The diagnosis was confirmed by ascending phlebography, and the thrombotic burden estimated with a newly developed scoring system. Receiver operating characteristics (ROC) curves calculated to demonstrate the discriminatory capacity of the methods, showed the area under the curves (AUCs) to be similar for the APC-PCI and D-dimer methods. However, in contrast to the D-dimer method, the APC-PCI method measures a well-defined analyte, a prerequisite for reliable comparisons of future clinical studies. The APC-PCI method appears to be particularly useful as a marker for detection of recently developed proximal thrombi. PMID- 11776307 TI - Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency. AB - The factor XII genes of two unrelated factor XII-deficient Japanese families were screened, and two novel mutations were identified. A heterozygous mutation (Q421K) was identified in the gene of a cross-reacting material (CRM)-negative patient with reduced FXII activity (entitled Case 1). No mutations were discovered in the other allele. Case 2 was a CRM-negative patient with severe FXII deficiency. In this case, a homozygous mutation (R123P) was discerned. Expression studies in Chinese Hamster Ovary (CHO) cells demonstrated accumulation of mutant Q421 K factor XII in the cell, and insufficient secretion, while the R123P mutant showed lower levels of accumulation than wild-type, and no evidence of secretion in culture supernatant. In the presence of proteasome inhibitor, all types of FXII (wild-type. Q421K, R123P) accumulated in the cells. Protease protection experiments using the microsomal fraction of these cell lines demonstrated that while 20% wild-type FXII (total wild-type:100%) and 10% R123P mutant (total R123P-type: 40%) were resistant to treatment with trypsin, 50% Q421K-type FXII (total Q421K-type:130%) remained resistant to digestion. From these results, we conclude that Q421K is less susceptible to proteasome degradation than wild-type, but is unable to exit the ER efficiently, resulting in insufficient secretion phenotype. In contrast, R123P is susceptible to proteasome degradation and is not secreted. PMID- 11776308 TI - Localization of blood coagulation factors in situ in pancreatic carcinoma. AB - Blood coagulation is activated commonly in pancreatic carcinoma but the role of the tumor cell in this activation is undefined. Immunohistochemical procedures were applied to fixed sections of 22 cases of resected adenocarcinoma of the pancreas to determine the presence of components of coagulation and fibrinolysis pathways in situ. Tumor cell bodies stained for tissue factor: prothrombin: and factors VII, VIIIc, IX, X, XII, and subunit "a" of factor XIII. Fibrinogen existed throughout the tumor stroma, and tumor cells were surrounded by fibrin. Staining for tissue factor pathway inhibitor, and plasminogen activators was minimal and inconsistent. Plasminogen activator inhibitors -1, -2, and -3 were present in the tumor stroma, and on tumor cells and vascular endothelium. Extravascular coagulation activation exists associated with pancreatic carcinoma cells in situ that is apparently unopposed by naturally occurring inhibitors or the plasminogen activator-plasmin system. We postulate that such local coagulation activation may regulate growth of this malignancy. These findings provide a rationale for testing agents that modulate the blood coagulation/fibrinolytic system (that inhibit tumor growth in other settings) in pancreatic carcinoma. PMID- 11776309 TI - Hepatic thrombopoietin mRNA is increased in acute inflammation. AB - The plasma concentration of thrombopoietin (TPO) in general is inversely related to the mass of platelets and megakaryocytes. However, reactive thrombocytosis of inflammatory disease is accompanied by elevated TPO levels. To investigate whether the rate of TPO mRNA expression is altered during acute inflammation, rats were injected with bacterial lipopolysaccharide (LPS). After 6 h, total RNA from liver and kidney was reverse transcribed and analyzed by competitive PCR for TPO and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). LPS-treated rats showed a significant increase in hepatic TPO mRNA concentration. The ratio of TPO to GAPDH mRNA was 3.5 +/- 0.6% in the livers of control rats and 8.3 +/- 2.0% in the livers of LPS-treated rats (mean +/- SD). Thus, reactive thrombocytosis of inflammatory disease might result from an increase in hepatic TPO production. Since platelets are involved in the immune reaction, reactive thrombocytosis may be a mechanism of host defense. PMID- 11776310 TI - A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function. AB - We have investigated the effect of a new Leu196Pro mutation, identified in the MIDAS-like domain of the beta3 integrin subunit in a patient with type II Glanzmann thrombasthenia, on beta3 integrin receptor function. Expression of the mutant beta3Pro196 subunit in CHO cells, either associated with recombinant human alphaIIb or alphav, resulted in normal biosynthesis of beta3 and heterodimerization with alphav or alphaIIb, but selectively interfered with alphaIIbbeta3 maturation and transport to the cell surface. Functional analysis of the beta3 mutant receptors revealed strong inhibition of alphavbeta3-mediated cell spreading on immobilized fibrinogen, focal contact formation, p125FAK phosphorylation and fibrin clot retraction, as opposed to normal alphaIIbbeta3 mediated cell interaction with immobilized fibrinogen, focal contact translocation and signaling. In contrast, antibody- or DTT-activated mutant aIIbbeta3 was unable to bind soluble fibrinogen or the ligand mimetic PAC-1 monoclonal antibody, but underwent a conformational change following RGD peptide binding as demonstrated by AP5-LIBS epitope expression. These results suggest that (1) the highly conserved TL196T motif in the beta3 integrin subunit is located in a domain structurally important for the exposure of a functional binding site for soluble fibrinogen; and (2) that the MIDAS-like contact site in beta3 is not involved in alphaIIbbeta3-mediated cell adhesion to immobilized fibrinogen, while it is essential for alphavbeta3-mediated interaction with this ligand. PMID- 11776311 TI - The type of factor VIII deficient plasma used influences the performance of the Nijmegen modification of the Bethesda assay for factor VIII inhibitors. AB - We have investigated the influence of the type of factor VIII deficient plasma used on the assay results of the Nijmegen modification of the Bethesda method for factor VIII inhibitors. Immuno depleted factor VIII deficient plasmas, lacking besides factor VIII also von Willebrand factor, gave decreased inhibitor titres compared to assay results with factor VIII deficient plasmas containing von Willebrand factor suggesting the need of the latter in the test system for the stability of factor VIII:C. Moreover the performance of the assay with immuno depleted plasma was contaminated in a certain type of this plasma by the presence of a factor VIII:C inhibitor. Chemically depleted factor VIII deficient plasma appeared to give falsely elevated titres when used in combination with other types of deficient plasmas as substrate plasma in the factor VIII:C assay due to the presence of activated factor Va in the preparation. Suggestions are described with respect to the observed limitations in order to obtain reliable results. PMID- 11776312 TI - Experimental arterial thrombosis in genetically or diet induced hyperlipidemia in rats--role of vitamin K-dependent clotting factors and prevention by low intensity oral anticoagulation. AB - To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia. PMID- 11776313 TI - Thrombin-mediated in vitro processing of pro-von Willebrand factor. AB - Von Willebrand factor (vWF) is synthesized in endothelial cells as pre-provWF and processed intracellularly to propeptide (vWFpp) and mature vWF. Building on previous studies indicating that recombinant provWF when infused into animals can also be processed extracellularly in vivo, we investigated the processing of provWF in vitro. Incubation of a recombinant provWF (rpvWF) preparation with canine and human vWF-deficient plasma induced a time-dependent decrease in provWF antigen and an increase in vWFpp antigen without changing total vWF antigen or collagen-binding activity. Multimer analysis showed the gradual transformation of the provWF multimers to mature vWF multimers and cleaved vWFpp was visualized on autoradiograms of SDS-polyacrylamide electrophoresis gels using 125-labeled provWF. Processing was facilitated by CaCl2 but prevented by a thrombin inhibitor and did not occur in prothrombin-depleted plasma. When recombinant provWF was incubated with increasing amounts of purified thrombin, the extent of provWF processing was dose-dependent. The specific cleavage of vWFpp was confirmed by immunoblots using an anti-vWFpp antibody and by amino terminal amino-acid analysis. Binding of provWF to collagen decreased the thrombin concentration necessary for propeptide removal to a concentration in the range of that found during blood clotting. Meizothrombin, an intermediate of prothrombin activation, was also able to induce dose-dependent removal of the propeptide from rpvWF. Hirudin preconditioning of vWF-deficient mice attenuated processing of infused rpvWF suggesting that thrombin plays a part in the processing events in vivo. PMID- 11776314 TI - Defect of heparin binding in plasma and recombinant von Willebrand factor with type 2 von Willebrand disease mutations. AB - The aim of our study was to characterise heparin-binding properties of mutated von Willebrand factor (VWF) in 24 patients plasmas with type 2 von Willebrand disease (VWD). and in 15 recombinant VWF (rVWF) with the corresponding mutations. Binding of mutated rVWF or plasma VWF was compared to that of WT-rVWF or normal pool plasma VWF. Four mutations, at positions C509, V551, R552 and R611 lead to significantly decreased binding to heparin in both plasma and rVWF. Interestingly, whereas these four residues are distant in the primary structure of VWF-A1domain, they are close to each other in its three-dimensional structure. Structural analysis suggested how folding problems and destabilisation due to these mutations could induce reorganisation of surface regions involved in heparin binding. In contrast, no heparin-binding defect was found associated with different type 2 VWF mutants, at positions G561, E596, I662, R543, R545, V553, R578 or L697. PMID- 11776315 TI - Identification of critical residues on thrombin mediating its interaction with fibrin. AB - Thrombin binding to fibrin may be important in localizing thrombin to the site of vascular injury. However, fibrin-bound thrombin retains its catalytic activity toward fibrinogen, and may be prothrombotic under certain conditions. A collection of 52 purified thrombin mutants was used to identify those residues mediating the thrombin-fibrin interaction. Comparison of fibrinogen clotting activity with fibrin binding activity identified twenty residues involved in fibrinogen recognition with four of these residues important in fibrin binding (Lys65, His66, Tyr71, Arg73). No mutant was identified with normal clotting activity and deficient fibrin binding, suggesting that these two properties are not readily dissociable. A DNA thrombin aptamer that binds to these residues was able to inhibit the thrombin-fibrin interaction, and displace thrombin that was already bound. Mapping of these fibrin-binding residues on thrombin revealed that they are localized within exosite I, and comprise a subset of the residues important in fibrinogen recognition. PMID- 11776316 TI - Effect of cardiolipin oxidation on solid-phase immunoassay for antiphospholipid antibodies. AB - Diagnostic assays for antiphospholipid antibodies are routinely performed on microtitre plates coated with cardiolipin. Here we show that contact between cardiolipin and NUNC-Immuno plates leads to extensive oxidation, generating a series of peroxy-cardiolipins which were identified by electrospray ionization mass spectrometry. To investigate the impact of oxidation on the antibody assay. cardiolipin was resolved into 12 molecular species, including oxidized species and non-oxidized species with different degrees of unsaturation. All 12 species reacted under anaerobic conditions with serum from patients with primary antiphospholipid syndrome. Immune reactivity was similar for tetralinoleoyl cardiolipin, trilinoleoyl-oleoyl-cardiolipin, and peroxycardiolipins, but somewhat lower for tristearoyl-oleoyl-cardiolipin. Oxidative treatment of cardiolipin with air, cytochrome c, or Cu2+/tert-butylhydroperoxide, either before or during the assay, did not enhance immune reactivity. Similar results were obtained with a monoclonal IgM from lupus-prone mice, that binds cardiolipin in the absence of protein cofactors. We conclude that the solid-phase assay for antiphospholipid antibodies can be supported by various oxidized and non oxididized molecular species of cardiolipin. PMID- 11776317 TI - A frameshift mutation in the human fibrinogen Aalpha-chain gene (Aalpha(499)Ala frameshift stop) leading to dysfibrinogen San Giovanni Rotondo. AB - We have investigated a 53-yr-old asymptomatic white man with decreased functional, but not immunologic, fibrinogen plasma levels together with prolonged thrombin and reptilase times, detected through routine coagulation studies prior to a surgical procedure. A new heterozygous single nucleotide deletion (C) at position Ala499 within the Aalpha-chain gene was identified, which predicted changes of the corresponding amino acids encoded by the subsequent portion of the exon V and the appearance of a premature stop codon at position 518 (Aalpha[499]Ala frameshift stop). The new dysfunctional fibrinogen, San Giovanni Rotondo variant, was confirmed in vivo by SDS-PAGE analysis of HPLC-purified fibrinogen chains. Mass spectrum examination of the abnormal HPLC-purified peak gave an estimated mass (56,088 Da) similar to that predicted by DNA analysis of the mutated Aalpha-chain gene (56,088 Da) and, after tryptic digestion, the truncated Aalpha-chain was shown only in the propositus, who also carried normal Aalpha-chain. In addition, mass spectrum analysis of the tryptic digest of the abnormal chain confirmed the presence of a new and unpaired cysteine at the last position that was predicted to form a disulfide bridge with human serum albumin. Immuno-blot analysis confirmed that fibrinogen San Giovanni Rotondo variant, but not normal fibrinogen. contained substantial amounts of albumin. Present findings confirm that truncated Aalpha-chain lacking part of the terminal domain may be incorporated into mature fibrinogen molecules and normally secreted in the bloodstream. PMID- 11776318 TI - Comparison of the responses of global tests of coagulation with molecular markers of neutrophil, endothelial, and hemostatic system perturbation in the baboon model of E. colisepsis--toward a distinction between uncompensated overt DIC and compensated non-overt DIC. AB - This study correlates changes in neutrophilic activity and endothelial injury with markers of hemostatic activity following the infusion of increasing concentrations of E. coli organisms. It focuses on the hemostatic response as a marker of microvascular injury and uses the response to increasing concentrations of E. coli to refine our definition of disseminated intravascular coagulation (DIC) and distinguish between a compensated (non-overt DIC) and uncompensated (overt DIC) response. We observed that the global coagulation tests reflected activation of the hemostatic system in a dose dependent manner (overt DIC) in the early phases (T+2 to 6 h) of the response to increasing concentrations of E. coli, but that they failed to do so in the late phases (T+ 24 to 48 h). We observed that molecular markers, soluble thrombomodulin and elastase, unlike thrombin/antithrombin and plasmin/antiplasmin complexes, remained elevated out to T+24 to 48 h indicating endothelial injury that persists beyond the initial inflammatory insult in compensated as well as uncompensated DIC. PMID- 11776319 TI - Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples. AB - We sought to assess the longitudinal stability of risk factors for atherosclerosis and thrombosis. including several coagulation. fibrinolysis, and inflammation factors, in frozen plasma samples stored at -70 degrees C for months or years. We reviewed data collected on 29 different control pools over periods ranging from 7 to 59 months for two functional assays (factor VII and fibrinogen) and seven antigen measurements (C-reactive protein. D-dimer, plasmin-alpha2 antiplasmin complex, plasminogen activator inhibitor-1, protein C, protein S, and tissue plasminogen activator), totaling more than 15,000 data points. Screening of the data using least squares regression revealed only sporadic associations between monthly means and time, with no consistent trends. Analysis by repeated measures and summary measure methods revealed no evidence of sample degradation over time for the factors studied. Our finding of longitudinal stability in the biochemical properties of frozen plasma strengthens the presumption of sample stability on which molecular epidemiologic studies are based. PMID- 11776321 TI - The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor, in rat models of venous and arterial thrombosis. AB - The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor (Ki = 4.9 nM) was evaluated in rat models of venous thrombosis combined with a bleeding time test and arterial thrombosis. After drugs were given by i. v. bolus injection plus a continuous infusion, the ID50, (a dose that exhibits 50% inhibition of thrombus formation over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.04 mg/kg plus 0.04 mg/kg/h, 0.1 mg/kg plus 0.4 mg/ kg/h, and 13.0 IU/kg plus 26.0 IU/kg/h, respectively, in the venous thrombosis study. The BT2 (a dose that causes 2-fold prolongation of bleeding time over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.9 mg/kg plus 0.9 mg/kg/h, 1.0 mg/kg plus 0.6 mg/kg/h, and 345.5 IU/kg plus 691.0 IU/kg/h in the rat tail transection model. The ratios of BT2/ID50 of AT 1459, argatroban, and dalteparin were 22.5, 10.0, and 26.6, respectively. In a rat model of arterial thrombosis induced by topical FeCl2 application, intravenous administration of AT-1459, argatroban, and dalteparin improved the vessel patency significantly (P < 0.01) at 0.6 mg/kg plus 0.6 mg/kg/h, 0.6 mg/kg plus 2.4 mg/kg/h, and 300 IU/kg plus 600 IU/kg/h, respectively. The oral antithrombotic effect of AT-1459 lasted for 6 after administering 30 mg/kg and improved the vessel patency significantly 1 h after administering the same dose in venous and arterial thrombosis models, respectively, with a rapid onset of action. Warfarin also inhibited thrombus weight and improved the vessel patency significantly after oral administration of 0.3 mg/kg for three consecutive days in the same study. The antithrombotic and hemorrhagic effects of all drugs studied were correlated with plasma concentration or clotting times. These results suggest that AT-1459 may be clinically useful as an orally available antithrombotic agent for the prevention of venous and arterial thrombosis. PMID- 11776320 TI - Crotalin, a vWF and GP Ib cleaving metalloproteinase from venom of Crotalus atrox. AB - Binding of von Willebrand factor (vWF) to a variety of extracellular matrix (ECM) components and to platelet glycoprotein (GP) Ib-IX-V complex is important in mediating platelet adhesion and aggregation in the early stage of hemostasis. We previously purified a potent antithrombotic protein, named crotalin, functionally acting as a GP lb antagonist (1). In this study, we further characterized crotalin as a P-I metalloproteinase with a molecular mass of 25 kDa as determined by gel filtration and two-dimensional SDS-PAGE. Crotalin is a vWF binding and cleaving metalloproteinase. In addition, crotalin cleaved platelet GP lb as judged by flow cytometry and Western blotting. The multiple effects of crotalin on vWF and platelet GP lb antagonized ristocetin-, but not collagen and thrombin induced platelet aggregation, suggesting that its effect is specific. We also found that crotalin autoproteolytically degraded to approximately 14 and approximately 10 kDa fragments in the presence of SDS. Interestingly, both degradation fragments, intact and reduced crotalin were able to bind vWF, suggesting the binding of crotalin to vWF is conformation-independent. In conclusion, the results presented further explain the potent antithrombotic effect of crotalin in vivo. In addition, the multiple effects of crotalin may be used as a tool to determine the binding motifs that are responsible for the vWF ECMs or vWF-GP lb interaction. PMID- 11776323 TI - Inactivation of plasminogen activator inhibitor-1 accelerates thrombolysis of a platelet-rich thrombus in rat mesenteric arterioles. AB - To investigate the role of active plasminogen activator inhibitor 1 (PAI-1) in the evolution of a microthrombus generated in the arteriolar microcirculation, the monoclonal antibody, 33H1F7, which transforms active PAI-1 to a tissue type plasminogen activator (t-PA) substrate, was evaluated in an arteriolar thrombosis model in the rat mesentery. Arterioles (200-300 um) were stimulated electrically to create an endothelial lesion; ADP was then perfused for 2 min to induce the formation of a platelet-rich thrombus which lysed spontaneously in 140 +/- 24 s. Two successive ADP superfusions produced comparable thrombi which lysed in comparable times. Different doses of 33H1F7 were infused to rats for 30 min and the dose which inactivates rapidly and totally active rat PAI-1 (300 microg/kg/min) was selected to be tested on the thrombosis model. Infusion of 33H I F7 beginning 10 min before the ADP application significantly reduced the lysis time in comparison to the control (123 +/- 30 s versus 169 +/- 33 s, P < 0.05, paired Student's t-test) and the cumulative thrombus area during the lysis period was decreased by 56 +/- 7%. These results demonstrate that inactivation of PAI-1 is able to accelerate lysis of a platelet-rich clot in a mesenteric arteriole of the rat. Thus active PAI-1 most likely participates to the resistance to thrombolysis in the arteriolar microcirculation and its inactivation may shorten ischemic periods after microvascular obstruction such as e.g. during cerebral stroke. PMID- 11776322 TI - A novel function of extraerythrocytic hemoglobin: identification of globin as a stimulant of plasminogen activator biosynthesis in human fibroblasts. AB - Following wounding, the surrounding fibroblasts migrate towards the clotted blood in the wounded space to form granulation tissue resulting in wound repair. One of the most abundant proteins in the wound is hemoglobin (Hb). The aim of the present study was to examine the effect of Hb on fibroblasts in producing components of the plasminogen-plasmin system which play an important role in wound healing. Human Hb A0 added to cultures of human fibroblasts elicited a dose dependent increase in fibrinolytic activity. ELISA demonstrated an increased fibrinolytic activity due to increased urokinase-type plasminogen activator (uPA). An increase in tissue-type PA was also detected, while the type-I PA inhibitor level remained unaffected. Globin showed a similar effect, while hemin and protoporphyrin IX exerted no effect. The influence of Hb was quenched when haptoglobin was added. Although northern blot analysis revealed no difference in uPA transcripts between stimulated and non-stimulated cells, immunoprecipitation experiments confirmed an increased uPA synthesis in Hb- and globin-treated cells, suggesting that enhanced expression is achieved through translational regulation. These findings suggest a potential role for globin in modulating cellular functions during the process of wound healing. PMID- 11776324 TI - The ability of poloxamers to inhibit platelet aggregation depends on their physicochemical properties. AB - Poloxamers, block copolymers of polyethylene glycol (PEG) and polypropylene glycol (PPG), are thought to reduce cell-cell adhesion during vascular disorders. We examined how the amphiphilic nature of these polymers may contribute to their ability to inhibit ADP-induced platelet aggregation. Four Poloxamers (184, 188, 335 and 338) with varying PEG and PPG block lengths were examined. Of these, Poloxamer 184 at 2 mM markedly inhibited platelet aggregation. We observed that: i) Typically, less than 10% of the platelet surface is covered by Poloxamers, and greater than 99% of the polymer either remains in solution or binds soluble components in blood plasma. ii) Increasing the PEG side-chain length does not significantly augment the ability of Polox-amers to inhibit platelet aggregation. iii) Poloxamer 184, but not Polox-amers 188 and 335, significantly reduces the ability of stimulated platelets to bind fibrinogen and antibody PAC-1. The study demonstrates that the physical adsorption of some Poloxamers may allow them to inhibit platelet aggregation. The inhibition mechanism involves either binding of Poloxamers to platelet GPIIb-IIIa or inhibition of cellular activation pathways. PMID- 11776325 TI - Dual effects of sulfated D-galactans from the red algae Botryocladia occidentalis preventing thrombosis and inducing platelet aggregation. AB - Sulfated D-galactans occur on the red algae Botryocladia occidentalis as three fractions that differ in their sulfate content. Fractions F2 and F3 are potent anticoagulants. Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. The inhibition potency increases simultaneously with the sulfate content of the fractions. The antithrombotic activity of these sulfated D-galactans was investigated on an experimental thrombosis model in which thrombus formation was induced by a combination of stasis and hypercoagulability. In contrast with heparin. the sulfated D-galactans showed a dual dose-response curve preventing thrombosis at doses up to approximately 0.5 mg/ kg body weight but losing the effect at higher doses. This unexpected behavior is probably due to a combined action of the sulfated D galactan as anticoagulant and also as a strong inducer of platelet aggregation. In platelet-depleted animals the antithrombotic activity at higher dose of sulfated D-galactan is restored and almost total inhibition of thrombus formation is achieved. The sulfated D-galactan has no hemorrhagic effect even at high doses, possibly as a consequence of its effect on platelet aggregation. At comparable dose heparin has an intense bleeding effect. These results indicate that new polysaccharides, with well-defined structures, can help to distinguish events, such as antithrombotic and anticoagulant activities, bleeding and platelet-aggregating effects, which are obscure when induced simultaneously by a single compound. PMID- 11776326 TI - Bemiparin and fluid flow modulate the expression, activity and release of tissue factor pathway inhibitor in human endothelial cells in vitro. AB - We investigated the localisation, gene expression, and activity of tissue factor pathway inhibitor (TFPI) in endothelial cells (EC) grown in static conditions or under shear stress, in the presence of unfractionated heparin (UFH) and two low molecular-weight heparins (LMWHs). dalteparin and bemiparin (a second generation of LMWHs). All three preparations induced increased release, cellular redistribution, and enhanced activity of TFPI on the cell surface in static EC. In EC grown under shear stress (0.27, 4.1 and 19 dyne/cm2) and incubated with each heparin for 24 h, the release of TFPI was significantly correlated with the level of flow for bemiparin and dalteparin, but not for UFH. For all three levels of flow tested, bemiparin induced the highest secretion and increase of both cellular TFPI and cell surface activity of the inhibitor. The expression of TFPI mRNA, determined by Northern blotting, was specifically modulated by heparins. All three preparations increased the expression of TFPI by 60 to 120% in EC under minimal flow, but only bemiparin enhanced TFPI mRNA in EC under the arterial flow. Immunogold electron microscopy revealed that EC exhibited strong cellular labelling for TFPI when grown under arterial flow in the presence of bemiparin. We conclude that in EC subjected to shear stress in vitro bemiparin is more efficient than UFH or dalteparin in modulating the expression. release and activity of TFPI. We therefore suggest that bemiparin may be superior over the conventional heparins in maintaining the anticoagulant properties of the endothelium. PMID- 11776327 TI - Extracellular signal-regulated kinase (ERK) activation is required for GP Ibalpha dependent endothelial cell migration. AB - The GP Ib complex can participate in endothelial cell (EC) migration on von Willebrand factor (vWF) or the mixed matrix of vWF and type I collagen (vWF/collagen). In this study, viper venom proteins alboaggregin (albo) A or B blocked GP Ibalpha, and echistatin inhibited alphavbeta3 binding. Albo A, B and echistatin inhibited EC migration on vWF and vWF/collagen. Albo B or the anti-GP Ibalpha monoclonal antibody (mAb) 1b1 did not affect the migration of smooth muscle cells or fibroblasts, which lack GP Ib. EC also migrate on albo A- or albo B-coated dishes. PD98059, which blocks ERK activation, abolished EC migration on vWF, vWF/collagen, collagen or albo B. Soluble albo A or 1b1 dramatically inhibited ERK activation during EC migration on vWF or albo B. Echistatin inhibited ERK activation on vWF and vitronectin (VN), but not albo B. Thus, in addition to alphavbeta3, EC GP Ibalpha initiates ERK activation, and regulates ERK-induced EC migration on vWF. PMID- 11776328 TI - Differential mechanisms of plasminogen activator inhibitor-1 gene activation by transforming growth factor-beta and tumor necrosis factor-alpha in endothelial cells. AB - Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (SERPIN) specific for tissue-type and urokinase-like plasminogen activators. High plasma PAI-1 activity is a risk factor for thrombotic diseases. Due to the short half life of PAI-1, regulation of PAI-1 gene expression and secretion of active PAI-1 into the blood stream is important for hemostatic balance. We have investigated transcriptional control of PAI-1 gene expression in bovine aortic endothelial cells (BAECs) and human cell lines using PAI-1 5' promoter-luciferase reporter assays. Contrary to the cytokine-induced up-regulation of PAI-1 mRNA and protein levels, we found that only transforming growth factor-beta (TGF-beta) was efficient in inducing PAI-1 promoter activation. Tissue necrosis factor-alpha (TNF-alpha) induced a small luciferase activity with the 2.5 kb PAI-1 promoter, but not with the PAI-800/4G/5G and p3TP-lux promoters. Next we investigated whether a lack of response to TNF-alpha was due to deficient signaling pathways. BAECs responded to TNF-alpha with robust NFkappaB promoter activation. TGF-beta activated the p38 MAP kinase, while TNF-alpha activated both the SAPK/JNK and p38 MAP kinases. The ERK1/2 MAP kinases were constitutively activated in BAECs. BAEC therefore responded to TNF-alpha stimulation with activation of the MAP kinases and the NFkappaB transcriptional factors. We further measured the messenger RNA stability under the influence by TGF-beta and TNF-alpha and found no difference. PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway, while TGF-beta is the most important cytokine for PAI-1 transcriptional activation through its 5' proximal promoter. PMID- 11776330 TI - The early course of D-dimer concentration following pulmonary artery embolisation. PMID- 11776331 TI - Comparison of a quantitative latex and a quantitative ELISA plasma D-dimer assay in the exclusion of segmental and subsegmental pulmonary embolism. PMID- 11776329 TI - Recombinant tissue factor pathway inhibitor prevents lipopolysaccharide-induced systemic hypotension in rats by inhibiting excessive production of nitric oxide. AB - Excessive production of nitric oxide (NO) by the inducible form of NO synthase (iNOS) plays a key role in the development of endotoxin shock. Tumor necrosis factor-alpha (TNF-alpha) induces iNOS, thereby contributing to the development of shock. We recently reported that recombinant tissue factor pathway inhibitor (r TFPI), an important inhibitor of the extrinsic pathway of the coagulation system, inhibits TNF-alpha production by monocytes. In this study, we investigated whether r-TFPI could ameliorate hypotension by inhibiting excessive production of NO in rats given lipopolysaccharide (LPS). Pretreatment of animals with r-TFPI prevented LPS-induced hypotension. Recombinant TFPI significantly inhibited the increases in both the plasma levels of NO2-/NO3- and lung iNOS activity 3 h after LPS administration. Expression of iNOS mRNA in the lung was also inhibited by intravenous administration of r-TFPI. However, neither DX-9065a, a selective inhibitor of factor Xa, nor an inactive derivative of factor VIIa (DEGR-F.Vlla) that selectively inhibits factor VIIa activity, had any effect on LPS-induced hypotension despite their potent anticoagulant effects. Moreover, neither the plasma levels of NO2-/NO3- nor lung iNOS activity were affected by administration of DX-9065a and DEGR-F.VIIa. These results suggested that r-TFPI ameliorates LPS induced hypotension by reducing excessive production of NO in rats given LPS and this effect was not attributable to its anticoagulant effects, but to the inhibition of TNF-alpha production. PMID- 11776332 TI - A normal serum CRP measurement does not exclude deep vein thrombosis. PMID- 11776333 TI - Ala147Thr and C+1542G polymorphisms in the TAFI gene are not asssociated with a higher risk of venous thrombosis in FV Leiden carriers. PMID- 11776334 TI - Effect of chronic angiotensin II type I receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic variables in patients with heart failure. PMID- 11776335 TI - The effects of vitamin K-antagonists on survival of patients with malignancy: a systematic analysis. PMID- 11776336 TI - Modification of von Willebrand disease after liver transplantation. PMID- 11776337 TI - Collection and transport of samples for laboratory testing in von Willebrand's disease (VWD): time for a reappraisal? PMID- 11776338 TI - How old is factor V Leiden mutation? PMID- 11776339 TI - Prevalence of factor V Leiden and prothrombin 20210A mutations in indigenous Australians. PMID- 11776340 TI - A family history of type 2 diabetes is associated with lower sensitivity to activated protein C in overweight and obese premenopausal women. PMID- 11776341 TI - Evidence for an association of the R485K polymorphism in the coagulation factor V gene with severe preeclampsia from screening 35 polymorphisms in 27 candidate genes. PMID- 11776342 TI - Successful use of argatroban as an anticoagulant in burn-related severe acquired antithrombin III deficiency after heparin failure. PMID- 11776343 TI - Angiopoietin-1 is normally expressed by periendothelial cells. PMID- 11776344 TI - Preventing surgical-site infections: the importance of timing and glucose control. PMID- 11776345 TI - The association of diabetes and glucose control with surgical-site infections among cardiothoracic surgery patients. AB - OBJECTIVE: To assess the importance of diabetes, diabetes control, hyperglycemia, and previously undiagnosed diabetes in the development of surgical-site infections (SSIs) among cardiothoracic surgery patients. SETTING: A 540-bed tertiary-care university-affiliated hospital. DESIGN: Prospective cohort and case control studies. PATIENTS: All patients having cardiothoracic surgery between November 1998 and September 1999 were eligible for participation. One thousand patients had preoperative hemoglobin A1c determinations. Seventy-four patients with SSIs were identified. RESULTS: Diabetes (odd ratio [OR], 2.76; P<.001) and postoperative hyperglycemia (OR, 2.02; P=.007) were independently associated with development of SSIs. Among known diabetics, elevated hemoglobin A1c values were not associated with a statistically significantly increased risk of infection; the mean A1c value was 8.44% among those with infections compared with 7.80% for those without (P=.09). Forty-two (6%) of 700 patients without prior diabetes history had evidence of undiagnosed diabetes; their infection rate was comparable to that of known diabetics (3/42 [7%] vs 17/300 [6%]; P=.72). An additional 30% of nondiabetics had elevated hemoglobin A1c determinations or perioperative hyperglycemia. CONCLUSIONS: Postoperative hyperglycemia and previously undiagnosed diabetes are associated with development of SSIs among cardiothoracic surgery patients. Screening for diabetes and hyperglycemia among patients having cardiothoracic surgery may be warranted to prevent postoperative and chronic complications of this metabolic abnormality. PMID- 11776346 TI - Risk factors for surgical-site infections following cesarean section. AB - OBJECTIVE: To identify risk factors associated with surgical-site infections (SSIs) following cesarean sections. DESIGN: Prospective cohort study. SETTING: High-risk obstetrics and neonatal tertiary-care center in upstate New York. PATIENTS: Population-based sample of 765 patients who underwent cesarean sections at our facility during 6-month periods each year from 1996 through 1998. METHODS: Prospective surgical-site surveillance was conducted using methodology of the National Nosocomial Infections Surveillance System. Infections were identified during admission, within 30 days following the cesarean section, by readmission to the hospital or by a postdischarge survey. RESULTS: Multiple logistic regression analysis identified four factors independently associated with an increased risk of SSI following cesarean section: absence of antibiotic prophylaxis (odds ratio [OR], 2.63; 95% confidence interval [CI95], 1.50-4.6; P=.008); surgery time (OR, 1.01; CI95, 1.00-1.02; P=.04); <7 prenatal visits (OR, 3.99; CI95, 1.74-9.15; P=.001); and hours of ruptured membranes (OR, 1.02; CI95, 1.01-1.03; P=.04). Patients given antibiotic prophylaxis had significantly lower infection rates than patients who did not receive antibiotic prophylaxis (P=02), whether or not active labor or ruptured membranes were present. CONCLUSION: Among the variables identified as risk factors for SSI, only two have the possibility to be changed through interventions. Antibiotic prophylaxis would benefit all cesarean patients regardless of active labor or ruptured membranes and would decrease morbidity and length of stay. Women's healthcare professionals also must continue to encourage pregnant women to start prenatal visits early in the pregnancy and to maintain scheduled visits throughout the pregnancy to prevent perinatal complications, including postoperative infection. PMID- 11776347 TI - An outbreak of coagulase-negative staphylococcal surgical-site infections following aortic valve replacement. AB - OBJECTIVES: To determine the cause of a coagulase-negative staphylococcal outbreak and to identify risk factors for surgical-site infections among patients following Medtronic Freestyle bioprosthesis implantation. DESIGN: Retrospective case-control study. SETTING: An 800-bed university referral center. PATIENTS: The cohort of 64 patients undergoing Freestyle valve replacement from September 1998 to December 1998. RESULTS: Seven patients developed infection (10.9% vs 1.1% during the preceding 8 months), including two with mediastinitis and five with endocarditis. There were no statistically significant differences between cases and controls with respect to age, gender, weight, underlying illness, preoperative hospital stay, duration of surgery, time on bypass, central venous catheter duration, National Nosocomial Infection Surveillance risk index, New York Heart Association class, albumin, or antibiotic prophylaxis. However, only three cases were documented to have received vancomycin prophylaxis. Of all staff evaluated, only surgical resident A was significantly associated with infection (odds ratio, 7.68; 95% confidence interval, 1.3-44.1; P=.02) Pulsed-field gel electrophoresis patterns on Staphylococcus epidermidis isolates from four of the six cases were identical. These cases were performed on different days. Surgical resident Awas the only staff member present in the operating room for all cases caused by the epidemic strain. This S epidermidis strain, however, was not isolated from operating room staff. CONCLUSION: A surgical resident was significantly associated with infection. However, the cause of this outbreak was likely multifactorial. Changes occurring during the investigation included institution of vancomycin as routine prophylaxis and modification of surgical technique, which contributed to the resolution of the outbreak. PMID- 11776348 TI - Risk factors for colonization with vancomycin-resistant enterococci in a Melbourne hospital. AB - OBJECTIVE: To determine risk factors for colonization with vancomycin-resistant enterococci (VRE) in a hospital outbreak. DESIGN: Outbreak investigation and case control study. SETTING: A referral teaching hospital in Melbourne, Australia. PARTICIPANTS: Cases were inpatients colonized (with or without clinical disease) with VRE between July 26 and November 28, 1998; controls were hospitalized patients without VRE. METHODS: Five cases of VRE were identified between July 26 and November 8, 1998, by growth of VRE from various sites. Active case finding by cultures of rectal swabs from patients surveyed in wards was commenced on July 26, after the first isolate of VRE. RESULTS: There were 19 cases and 66 controls. All the VRE identified were vanB, and all were Enterococcus faecium. One molecular type predominated (18/19 cases). In a logistic-regression model, being on the same ward as a VRE case was the highest risk factor (odds ratio [OR], 82; 95% confidence interval [CI95], 5.7-1,176; P=.001). Having more than five antibiotics (OR, 11.9; CI95 1.1-129.6; P<.05), use of metronidazole (OR, 10.9; CI95, 1.7-69.8; P=.01), and being a medical patient (OR, 8.1; CI95, 1.4-47.6; P<.05) also were significant. Intensive care unit admission was associated with decreased risk (OR, 0.1; CI95, 0.01-0.8; P<.05). CONCLUSION: Our findings are consistent with an acute hospital outbreak. Monitoring and control of antibiotic use, particularly metronidazole, may reduce VRE in our hospital. Ongoing surveillance and staff education also are necessary. PMID- 11776349 TI - Molecular epidemiology of an outbreak of Serratia marcescens in a neonatal intensive care unit. AB - OBJECTIVE: To investigate and control a biphasic outbreak of Serratia marcescens in a neonatal intensive care unit (NICU). DESIGN: Epidemiological and laboratory investigation of the outbreak. SETTING: The NICU of the 1,470-bed teaching hospital of the University "Federico II," Naples, Italy. PATIENTS: The outbreak involved 56 cases of colonization by S marcescens over a 15-month period, with two epidemic peaks of 6 and 3 months, respectively. Fourteen (25%) of the 56 colonized infants developed clinical infections, 50% of which were major (sepsis, meningitis, or pneumonia). METHODS: Epidemiological and microbiological investigations, analysis of macrorestriction pattern of genomic DNA through pulsed-field gel electrophoresis (PFGE) of clinical and environmental isolates, and institution of infection control measures. RESULTS: Analysis of macrorestriction patterns of genomic DNA by PFGE demonstrated that the vast majority of S marcescens isolates, including three environmental strains isolated from two handwashing disinfectants and the hands of a nurse, were of the same clonal type. The successful control of the outbreak was achieved through cohorting of noncolonized infants, isolation of S marcescens-infected and colonized infants, and an intense educational program that emphasized the need for adherence to glove use and handwashing policies. The NICU remained open to new admissions. CONCLUSIONS: Outbreaks caused by S marcescens are very difficult to eradicate. An infection control program that includes molecular typing of microorganisms and the proper dissemination among staff members of the typing results is likely to be very effective in reducing NICU-acquired infections and in controlling outbreaks caused by S marcescens, as well as other multiresistant bacteria. PMID- 11776350 TI - An in-use evaluation of an alcohol-based pre-surgical hand disinfectant. AB - OBJECTIVE: To determine whether alcohol hand disinfection is an effective alternative to traditional agents for the pre-surgical scrub. DESIGN: A prospective clinical trial of a 70% isopropanol pre-surgical hand disinfectant. SETTING: The operating room suites at two hospital sites in British Columbia. METHODS: Cases were selected to evaluate both short and longer procedures. The hand disinfectant was compared to agents in current use as surgical scrubs (4% chlorhexidine and 7.5% povidone-iodine). Surgical technique and glove use were not modified. Pre- and postoperative fingertip impression and "glove-juice" cultures were used to determine microbial burden, and hands were evaluated for skin integrity. RESULTS: There was no statistical difference between the microbial hand counts following use of the alcohol-based product or the current agents, for cases less than 2 hours' duration. Comparison of longer surgical cases revealed significantly better pre- and postoperative culture results with the alcohol hand rinse, but analysis of matched pairs showed no significant difference in microbial counts. The alcohol hand rinse was equivalent to the operative scrub in terms of skin integrity and user acceptability. CONCLUSION: An alcohol hand rinse was equivalently effective in reducing microbial hand counts as the traditional pre-surgical scrub, both immediately after hand disinfection and at the end of the surgical procedure. PMID- 11776351 TI - In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters. AB - OBJECTIVE: To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces. DESIGN: Experimental trial. METHODS: Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens with Staphylococcus epidermidis or Staphylococcus aureus culture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria. RESULTS: Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective against Candida species and Pseudomonas aeruginosa. Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged with S aureus 7 and 14 days' postimplant (P<.05). Repeated in vitro exposure of S epidermidis culture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistant S epidermidis in vivo (P<.05). CONCLUSIONS: Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device. PMID- 11776352 TI - Appropriateness of use of indwelling urinary catheters in patients admitted to the medical service. AB - Of 836 medical admissions evaluated over a 1-month period, 89 (10.7%) had a urinary catheter placed within 24 hours; 34 placements (38%) had no justifiable indication. Risk for inappropriate catheterization was independent of age, gender, functional status, and mental status at admission. Preventive measures should focus on increasing awareness among healthcare providers. PMID- 11776353 TI - Pseudo-outbreak of Mycobacterium scrofulaceum linked to cross-contamination with a laboratory reference strain. AB - Mycobacterium scrofulaceum was isolated from three clinical specimens over a period of 2 months. In the preceding 10 years, the institution had not reported any cases of this unusual mycobacterium. Investigation and confirmatory molecular testing indicated a laboratory control strain to be the source of contamination. PMID- 11776354 TI - Application of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients: impact on reducing the use of glycopeptides. AB - We evaluated the impact of applying the Infectious Diseases Society of America guidelines for febrile neutropenic patients in reducing the use of glycopeptides. Forty-five prior episodes of febrile neutropenia were compared to 97 episodes seen after application of the guidelines. Glycopeptide use was reduced from 73% to 43% of episodes (P=.0008), without changes in outcome. PMID- 11776355 TI - Bacterial contamination of fabric stethoscope covers: the velveteen rabbit of health care? AB - To determine if fabric stethoscope covers pose an infection control problem, we studied how they are cared for by our healthcare workers and performed microbiological investigations on 22 covers collected over a 3-week period. Our study suggests that fabric stethoscope covers represent a potential infection control problem because they are used for prolonged periods, are infrequently laundered, and are contaminated with bacteria. PMID- 11776356 TI - Physician preferences for continuing medical education with a focus on the topic of antimicrobial resistance: Society for Healthcare Epidemiology of America. AB - OBJECTIVE: To determine the type of media preferred for continuing medical education (CME) and to assess the factors that affect physician preferences for CME in general and on the special topic of antimicrobial resistance. DESIGN: A voluntary survey of the membership of the Society for Healthcare Epidemiology of America, Inc. (SHEA). METHODS: SHEA, in collaboration with other medical societies and with technical assistance from the Centers for Disease Control and Prevention, designed and mailed the survey to its membership. The survey included questions about media used, preferred, and of interest to try for CME delivery in general and on the topic of antimicrobial resistance in specific. The survey also included demographic and general questions, such as work environment, percentage of time in direct patient care, and experience treating patients with antimicrobial-resistant pathogens. RESULTS: 225 SHEA members completed the survey. The majority of physicians were in clinical practice (59%) and worked in a hospital (57%). The median year of graduation from medical school was 1979 (range, 1951-1999). CME subject matter (46%) was ranked as the most important factor affecting media preference. Journal articles (52%) were the most frequently used educational medium; local grand rounds (53%) and regional meetings (53%) were the most preferred media. CD-ROM (56%) and the Internet (46%) were selected as media of greatest interest to try. On the topic of antimicrobial resistance, the most frequently used and the preferred medium was journal articles (67% and 87%, respectively). Most (94%) had received an educational update on current antimicrobial resistance issues within the past year. Stratification of the data by graduation date revealed no significant differences in the medical education media used most (F=0.59, degrees of freedom [dfl=4, P=.6715) or preferred by SHEA members in general or on the topic of antimicrobial resistance (F=1.99, df=4, P=.0982). CONCLUSIONS: This study provides an understanding of how physicians learn, prefer to learn, and implement best practices for optimal patient outcomes in decreasing the spread of antimicrobial resistance. PMID- 11776357 TI - Developmental change in auditory preferences for speech stimuli in Japanese infants. AB - The developmental change in auditory preferences for speech stimuli was investigated for Japanese infants aged 4-14 months old. We conducted three experiments using two speech pairs in the head-turn preference procedure. Infant directed (ID) speech and adult-directed (AD) speech stimuli were used in a longitudinal study (Experiment 1) and a cross-sectional study (Experiment 2). Native (Japanese) and non-native (English) speech stimuli were used in a cross sectional study (Experiment 3). In all experiments, infants demonstrated a developmental change in their listening preference. For the ID/AD speech pair used in Experiments 1 and 2, infants show a U-shaped developmental shift with three developmental stages: Stage 1, in which very young infants tend to prefer ID speech over AD speech; Stage 2, in which the preference for ID speech decreases temporarily; and Stage 3, in which older infants again show a consistent preference for ID speech. For the native/non-native speech pair, there is a tendency for an increased preference for native speech over non-native speech, although infants did not demonstrate a U-shaped pattern. The difference in developmental pattern between the two types of speech pairs was discussed. PMID- 11776358 TI - A comparison of self-reported hearing loss and audiometry in a cohort of New York farmers. AB - The New York State Farm Family Health and Hazard Surveillance was conducted to assess the health status and safety practices among year-round adult farmers and farm residents in New York State and included a telephone interview survey of 1,727 persons from 552 farms. To determine the extent to which self-reported hearing loss is in agreement with audiometry, a subset of 376 participants who completed a hearing loss interview and pure-tone audiometry was analyzed. Thirty six percent of the participants had self-reported hearing loss, defined as at least some difficulty hearing in one or both ears. The prevalence of audiometric hearing impairment, defined as a threshold average greater than 25 dB hearing level, was 9% for the binaural low-frequency average (500, 1000, and 2000 Hz), 29% for the binaural mid-frequency average (1000, 2000, 3000, and 4000 Hz), and 47% for the binaural high-frequency average (3000, 4000, 6000, and 8000 Hz). Agreement between self-report and audiometry was highest for the binaural mid frequency average (kappa statistic 55%, sensitivity 77%, and specificity 82%). Self-reported hearing loss was found to be a moderately good measure of hearing impairment. We conclude that a simple questionnaire focusing on hearing difficulty is a useful and valid tool for conducting epidemiologic studies of farmers. Whenever possible, a substudy using audiometry should be conducted. PMID- 11776359 TI - Effects of CIC hearing aids on auditory localization by listeners with normal hearing. AB - An experiment was conducted to determine the effects of completely-in-the-canal (CIC) hearing aids on auditory localization performance. Six normal-hearing listeners localized a 750-ms broadband noise from loudspeakers ranging in azimuth from -180 degrees to +180 degrees and in elevation from -75 degrees to +90 degrees. Independent variables included the presence or absence of the hearing aid and the elevation of the source. Dependent measures included azimuth error, elevation error, and the percentage of trials resulting in a front-back confusion. The findings indicate a statistically significant decrement in localization acuity, both in azimuth and elevation, occasioned by the wearing of CIC hearing aids. However, the magnitude of this decrement was small compared to those typically caused by other ear-canal occlusions, such as earplugs, and would probably not engender mislocalization of real-world sounds. PMID- 11776360 TI - The relationship between perception and acoustics for a high-low vowel contrast produced by speakers with dysarthria. AB - This study was designed to explore the relationship between perception of a high low vowel contrast and its acoustic correlates in tokens produced by persons with motor speech disorders. An intelligibility test designed by Kent, Weismer, Kent, and Rosenbek (1989a) groups target and error words in minimal-pair contrasts. This format allows for construction of phonetic error profiles based on listener responses, thus allowing for a direct comparison of the acoustic characteristics of vowels perceived as the intended target with those heard as something other than the target. The high-low vowel contrast was found to be a consistent error across clinical groups and therefore was selected for acoustic analysis. The contrast was expected to have well-defined acoustic measures or correlates, derived from the literature, that directly relate to a listeners' responses for that token. These measures include the difference between the second and first formant frequency (F2-F1), the difference between F1 and the fundamental frequency (FO), and vowel duration. Results showed that the acoustic characteristics of tongue-height errors were not clearly differentiated from the acoustic characteristics of targets. Rather, the acoustic characteristics of errors often looked like noisy (nonprototypical) versions of the targets. Results are discussed in terms of the test from which the errors were derived and within the framework of speech perception theory. PMID- 11776361 TI - Evaluation of a stuttering treatment based on reduction of short phonation intervals. AB - This paper reports the results of an efficacy study of a stuttering treatment program known as Modifying Phonation Intervals (MPI), which trains stuttering speakers to reduce the frequency of relatively short phonation intervals (PIs) during connected speech across speaking tasks and situations. Five young adult male stuttering speakers were treated in this computer-based program that systematically trains speakers to reduce selected short PIs found to functionally control stuttering. The treatment process was evaluated using multiple-baseline designs. Treatment was largely self-managed and based on a performance-contingent schedule of within-clinic speaking tasks (Establishment), beyond-clinic speaking tasks (Transfer), and systematic decreases in assessment occasions (Maintenance). Assessments were made at regular intervals before, during, and after treatment. All speakers achieved stutter-free and natural-sounding speech during within- and beyond-clinic speaking tasks at the completion of Maintenance. All were tested 12 months after completion of Maintenance, and all maintained the results. The findings from this study suggest that this procedure may make a significant contribution to stuttering treatment practice. PMID- 11776362 TI - Quantification of static and dynamic supraglottic activity. AB - For estimating supraglottic compression in disordered voice production, categorical rating scales of true vocal fold coverage by supraglottic structures are the current standard. Quantification of change in the position of supraglottic structures compared to no supraglottic activity would be a better method for distinguishing between and within voice-disordered groups. This study developed a method for quantifying static supraglottic activity and extent of false vocal fold (FVF) motion during dynamic supraglottic activity. Twelve control participants and 12 individuals with voice disorders (6 with complaints of vocal fatigue and 6 with vocal fold nodules) were enrolled in the study. These individuals participated in a transnasal fiberoptic laryngeal examination in which various speech tasks were recorded. Single-frame images were selected to represent the positions of minimum and maximum supraglottic compression for each speech task. Two individuals rated these single-frame images using a categorical rating scale. Two other individuals measured the anterior-to-posterior (A-P) distance, vocal fold length, and vocal fold area. A-P and FVF compression were derived from these three measures. Reliability was demonstrated between judges for the ratings and between and within judges for the measures. Significant differences in normalized static supraglottic compression measures corresponded to the rating scale categories. Significant differences in normalized dynamic supraglottic compression measures corresponded to the differences in category ratings between minimum and maximum compression. Using the normalized measures, the voice-disordered groups demonstrated significantly greater static A-P compression (t test, p < .03) than did the control participants. These results suggest that static supraglottic activity may be diagnostic of voice disorder. Normalized dynamic FVF compression ratios were not significantly different between groups. This supports a previous hypothesis that dynamic supraglottic activity serves as an articulatory function at the level of the larynx and is part of the linguistic/phonemic system, rather than evidence of disordered laryngeal function. PMID- 11776363 TI - Covariation of cochlear implant users' perception and production of vowel contrasts and their identification by listeners with normal hearing. AB - This study investigates covariation of perception and production of vowel contrasts in speakers who use cochlear implants and identification of those contrasts by listeners with normal hearing. Formant measures were made of seven vowel pairs whose members are neighboring in acoustic space. The vowels were produced in carrier phrases by 8 postlingually deafened adults, before and after they received their cochlear implants (CI). Improvements in a speaker's production and perception of a given vowel contrast and normally hearing listeners' identification of that contrast in masking noise tended to occur together. Specifically, speakers who produced vowel pairs with reduced contrast in the pre-CI condition (measured by separation in the acoustic vowel space) and who showed improvement in their perception of these contrasts post-CI (measured with a phoneme identification test) were found to have enhanced production contrasts post-CI in many cases. These enhanced production contrasts were associated, in turn, with enhanced masked word recognition, as measured from responses of a group of 10 normally hearing listeners. The results support the view that restoring self-hearing allows a speaker to adjust articulatory routines to ensure sufficient perceptual contrast for listeners. PMID- 11776364 TI - Vocal development of 9-month-old babies with cleft palate. AB - This study compared the prelinguistic vocal development of 9-month-old babies with unrepaired cleft palate (n = 30) and age-matched peers (n = 15). Samples of the babies' spontaneous vocalizations were obtained while they interacted with their primary caregiver during play. The groups were compared on a number of variables including (a) canonical babbling ratios, (b) percentage of babies who reached the canonical babbling stage by 9 months, (c) syllable and segmental aspects of babbling, and (d) vocal frequency. Results indicated that the babies with cleft palate had smaller canonical babbling ratios than their age-matched peers, with just 57% of the babies with cleft palate reaching the canonical babbling stage by 9 months compared to 93% of the noncleft babies. Although syllable types and length were similar for the two groups, differences were noted for consonant characteristics. The babies with cleft palate had smaller consonant inventories, with fewer stops, glides, and velars noted. Glottals occurred more frequently in the vocalizations of the babies with cleft palate. Finally, no statistically significant difference was noted in the number of vocalizations produced by the two groups. Some possible explanations for why babies with cleft palate are delayed in babbling are explored. PMID- 11776365 TI - Effects of levodopa on laryngeal muscle activity for voice onset and offset in Parkinson disease. AB - The laryngeal pathophysiology underlying the speech disorder in idiopathic Parkinson disease (IPD) was addressed in this electromyographic study of laryngeal muscle activity. This muscle activity was examined during voice onset and offset gestures in 6 persons in the early stages of IPD who were not receiving medication. The purpose was to determine (a) if impaired voice onset and offset control for speech and vocal fold bowing were related to abnormalities in laryngeal muscle activity in the nonmedicated state and (b) if these attributes change with levodopa. Blinded listeners rated the IPD participants' voice onset and offset control before and after levodopa was administered. In the nonmedicated state, the IPD participants' vocal fold bowing was examined on nasoendoscopy, and laryngeal muscle activity levels were compared with normal research volunteers. The IPD participants were then administered a therapeutic dose of levodopa, and changes in laryngeal muscle activity for voice onset and offset gestures were measured during the same session. Significant differences were found between IPD participants in the nonmedicated state: those with higher levels of muscle activation had vocal fold bowing and greater impairment in voice onset and offset control for speech. Similarly, following levodopa administration, those with thyroarytenoid muscle activity reductions had greater improvements in voice onset and offset control for speech. In this study, voice onset and offset control difficulties and vocal fold bowing were associated with increased levels of laryngeal muscle activity in the absence of medication. PMID- 11776366 TI - An acoustical study of the fricative /s/ in the speech of individuals with dysarthria. AB - This paper reports on measurements of several acoustic attributes of the fricative consonant /s/ produced in word-initial position by normally speaking adults and by speakers with neuromotor dysfunctions. Several acoustic properties are evaluated: the spectrum shape of the fricative and its amplitude in relation to the following vowel, the presence or absence of voicing, the time variation of the spectrum during the fricative and in the transition to the following vowel, and the presence of inappropriate acoustic patterns preceding the /s/. Some of these properties are based on quantitative measurements of the spectrum of the /s/, and others are based on observations of the time-varying acoustic patterns in spectrograms. For the individuals with dysarthria, deviations of each of these properties from the normal range are interpreted in terms of specific deficits in the control of the speech-production system. For the most part, these parameters are highly correlated with the speakers' overall intelligibility, with the intelligibility of words containing the fricative /s/, and with perceptual ratings of the adequacy of the fricative production. The parameters that show the best correlation with intelligibility and perceptual ratings are (a) measures of deviations from normalcy in the time variation of the acoustic pattern within the consonant and at the consonant-vowel boundary and (b) the spectrum shape of the frication noise. These acoustic parameters are related to deviations in the temporal pattern of control of the articulators in producing fricative-vowel sequences and to lack of fine control of the tongue blade in achieving an appropriate target configuration for the fricative. PMID- 11776367 TI - An acoustic analysis of excellent female esophageal, tracheoesophageal, and laryngeal speakers. AB - Acoustic data for female esophageal speakers is sparse, particularly with regard to characteristics of female tracheoesophageal speakers. This study quantified and compared six acoustic characteristics of excellent female tracheoesophageal (TE), standard esophageal (SE), and laryngeal (LA) speakers. Results indicated there were no significant differences between TE and SE speakers with regard to mean F0 of sustained /a/, mean F0 (reading), signal-to-noise ratio, total duration of passage read, number of pauses, or syllables per minute. Significant differences were found between LA speakers and both alaryngeal groups for all variables, with the exception of mean F0 (reading). PMID- 11776368 TI - Learning new words: phonotactic probability in language development. AB - Though the influences of syntactic and semantic regularity on novel word learning are well documented, considerably less is known about the influence of phonological regularities on lexical acquisition. The influence of phonotactic probability, a measure of the likelihood of occurrence of a sound sequence, on novel word learning is investigated in this study. Thirty-four typically developing children (from ages 3 years 2 months to 6 years 3 months) participated in a multitrial word-learning task involving nonwords of varying phonotactic probability (common vs. rare) paired with unfamiliar object referents. Form and referent learning were tested following increasing numbers of exposures (1 vs. 4 vs. 7) and following a 1-week delay. Correct responses were analyzed to determine whether phonotactic probability affected rate of word learning, and incorrect responses were analyzed to examine whether phonotactic probability affected the formation of semantic representations, lexical representations, or the association between semantic and lexical representations. Results indicated that common sound sequences were learned more rapidly than rare sound sequences across form and referent learning. In addition, phonotactic probability appeared to influence the formation of semantic representations and the association between semantic and lexical representations. These results are integrated with previous findings and theoretical models of language acquisition. PMID- 11776369 TI - Sensitive periods differentiate processing of open- and closed-class words: an ERP study of bilinguals. AB - The goal of this study was to test the hypothesis that neural processes for language are heterogeneous in their adaptations to maturation and experience. This study examined whether the neural processes for open- and closed-class words are differentially affected by delays in second-language immersion. In English, open-class words primarily convey referential meaning, whereas closed-class words are primarily related to grammatical information in sentence processing. Previous studies indicate that event-related brain potentials (ERPs) elicited by these word classes display nonidentical distributions and latencies, show different developmental time courses, and are differentially affected by early language experience in Deaf individuals. In this study, ERPs were recorded from 10 monolingual English speakers and 53 Chinese-English bilingual speakers who were grouped according to their age of immersion in English: 1-3, 4-6, 7-10, 11-13, and >15 years of age. Closed-class words elicited an N280 that was largest over left anterior electrode sites for all groups. However, the peak latency was later (>35 ms) in bilingual speakers immersed in English after 7 years of age. In contrast, the latencies and distributions of the N350 elicited by open-class words were similar in all groups. In addition, the N400, elicited by semantic anomalies (open-class words that violated semantic expectation), displayed increased peak latencies for only the later-learning bilingual speakers (>11 years). These results are consistent with the hypothesis that language subprocesses are differentially sensitive to the timing of second-language experience. PMID- 11776370 TI - Is processing speed related to severity of language impairment? AB - Children with specific language impairment (SLI) typically respond more slowly on many tasks than do their typically developing peers. This paper addresses the question of whether speed of response is linearly related to severity of language impairment as measured by standardized test score. To address this question, we performed post hoc analyses of data from a study on lexical processing involving 66 children with SLI (mean age 6 years 9 months) and 66 typically developing children matched for age and nonverbal IQ. Response times derived from a series of tasks were correlated with language test scores. None of the Pearson correlations reached significance when corrected for number of correlations run, nor did a canonical correlation analysis reach significance. If these results are replicated in other studies, then they suggest that there is no direct linear relation between speed of processing and severity of language impairment as it is estimated from scores on standardized tests of language. PMID- 11776371 TI - Evaluating the morphological competence of children with severe speech and physical impairments. AB - Reports present mixed findings on the extent to which the development of receptive language skills in children with severe speech and physical impairments (SSPI) is compromised by their difficulty with speaking (V. W. Berninger & B. M. Gans, 1986; D. V. M. Bishop, B. Byers Brown, & J. Robson, 1990; O. Udwin & W. Yule, 1990). In this study, grammaticality judgments were used to measure the sensitivity of 4 school-age children with SSPI to different morphological errors. These errors included violations of agreement between the subject and auxiliary verbs (e.g., she are falling), the marking of aspect (e.g., she is play the horn), and the marking of past tense on regular and irregular verbs (e.g., he jump, he fall, he falled). Performance of the participants with SSPI was compared to groups of typically developing children and adults. Results indicated that children in the SSPI and control groups made similar judgments. All groups showed high levels of sensitivity to agreement violations, aspect-marking errors, and tense-marking errors involving irregular verbs. Participants with SSPI had greater difficulty detecting tense-marking errors involving regular verbs. Implications for improving clinical assessments within this population are discussed. PMID- 11776372 TI - Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. AB - Intravenous (i.v.) administration of a lipopolyplex consisting of a ternary complex of DOTAP:cholesterol cationic liposomes, protamine sulfate, and noncoding plasmid DNA (LPD-pDNA) is capable of stimulating a potent Th-1 cytokine response and inhibiting the growth of established tumors in mice. Both activities are mainly elicited by unmethylated CpG motifs in the plasmid DNA (pDNA) component, which are bacterial in origin. Since oligodeoxynucleotides (ODN) that possess a consensus immunostimulatory CpG motif of RRCpGYY (R is purine and Y is pyrimidine) can mimic the immunostimulatory actions of bacterial DNA, we hypothesized that i.v. administration of LPD prepared with GpG-ODN would mimic the ability of LPD-pDNA to stimulate Th-1 cytokines and antitumor activity and provide an improved vector for probing the immune mechanisms underlying the observed antitumor effects. These hypotheses were tested for the treatment of established 24JK experimental pulmonary metastases that are syngeneic in C57BL/6 mice. Mice treated with LPD containing 25 microg of the prototypical phosphodiester (PO) CpG-ODN 1668 (tccatGACGTTcctgatgct, motif capitalized) demonstrated a dramatic reduction in lung tumor burden (>80% inhibition, P<0.01) compared to dextrose-treated controls. The antitumor effect was dependent on the CpG dinulceotide and correlated with the ability to stimulate serum Th-1 cytokines (TNF-alpha, IL-12, and IFN-gamma). Both activities required assembly of CpG-ODN in a cationic liposome/DNA complex (lipoplex) or the LPD lipopolyplex. LPD delivery of both PO-1668 and phosphorothioated (PS)-1668 stimulated a greater cytokine response compared to delivery of free ODN. Furthermore, within the LPD complex, both PO- and PS-1668 had similar ability to stimulate Th-1 cytokines with respect to potency and duration of response, thus eliminating the need for the PS modification. In tumor cell lysis assays, LPD-CpG DNA stimulated development of an acquired, tumor-specific CD8+ cytotoxic T-lymphocyte (CTL) activity that was dependent on CpG DNA. LPD was also capable of stimulating NK activity; however, this was not dependent on CpG DNA. Only formulations that concomitantly stimulated NK activity and CpG-specific, Th-1 cytokine were capable of stimulating the development of tumor-specific CTL activity and significant inhibition of tumor growth. Thus, we propose a model where CpG DNA in complex with cationic liposome-based lipoplexes or lipopolyplexes stimulates antitumor NK activity and CpG-stimulated Th-1 cytokine production. The combination of these two activities of the innate immune system subsequently direct the development of an acquired, tumor-specific CTL response that in total are effective for inhibiting the growth of established tumors in mice. PMID- 11776373 TI - Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia. AB - Heat shock proteins are recognized as significant participants in immune reactions. In this study, we have demonstrated that the cell surface presentation of MHC class I antigen was increased in tandem with increased heat shock protein 70 (HSP70) expression and the immunogenicity of rat T-9 glioma cells was enhanced by hyperthermia. T-9 cells showed growth inhibition for 24 h after the heat treatment at 43 degrees C for 1 h in vitro, but then resumed a normal growth rate. HSP70 expression reached a maximum at 24 h after heating. Flow cytometric analysis revealed a significant increase in MHC class I antigen on the surface of the heated cells. The augmentation of MHC class I surface expression started 24 h after heating and reached a maximum 48 h after heating. The expression of other immunologic mediators, such as intracellular adhesion molecule-1 (ICAM-1) and MHC class II antigens, did not increase. In an in vivo experiment using immunocompetent syngeneic rats (F344), growth of the heated T-9 cells, with augmentation of MHC class I antigen surface expression, was significantly inhibited, while the cells grew progressively in nude rats (F344/N Jcl-rnu). Furthermore, compared with lymphocytes from non-immunized (PBS only injection) rats or rats injected with non-heated T-9 cells, the splenic lymphocytes of the rats in which the heated T-9 cells were injected displayed specific cytotoxicity against T-9 cells. These results suggest that HSP70 is an important modulator of tumor cell immunogenicity, and that hyperthermic treatment of tumor cells can induce the host antitumor immunity via the expression of HSP70. These results may benefit further efforts on developing novel cancer immunotherapies based on hyperthermia. PMID- 11776374 TI - Immunoglobulin genes expressed by B-lymphocytes infiltrating cervical carcinomas show evidence of antigen-driven selection. AB - Lymphocyte infiltration is often present in cervical cancer lesions, possibly reflecting an ongoing (but ineffective) immune response to the tumour. B lymphocytes are the predominant lymphocyte infiltrate in pre-malignant cervical lesions, where they are thought to comprise the host immune response to active human papillomavirus (HPV) infection. Although B cells are less frequently detected in cervical tumours, a high proportion of terminally differentiated plasma cells expressing tumour-specific immunoglobulin (Ig) remain. The antigen specificity and functional significance of the antibody response to cervical tumours is unknown. As part of a study to characterise the antibodies expressed by the tumour-infiltrating B cells (TIL-B) in cervical tumours using antibody phage display, we examined expressed Ig gene sequences to determine if there was molecular evidence of a selective response to antigenic changes in the transformed epithelial cells. We found that biased variable region gene usage by the B cells and the rate of somatic hypermutation in the rearranged Ig heavy chain variable regions (VH) both indicated antigenic selection of the B cells. We also found evidence of affinity maturation, as indicated by the detection of antibodies of the IgG1, IgG2 and IgA isotypes, and possible clonal selection of the Ig receptors. These data support the notion that B-lymphocytes and plasma cells infiltrating cervical carcinomas are the result of an antigen-induced response to HPV infection or transformation. PMID- 11776375 TI - Improved survival in tumor-bearing SCID mice treated with interferon-gamma inducible protein 10 (IP-10/CXCL10). AB - Tumor growth requires angiogenesis, which in turn requires an imbalance in the presence of angiogenic and angiostatic factors. We have shown that the CXC chemokine family, consisting of members that are either angiogenic or angiostatic, is a major determinant of tumor-derived angiogenesis in non-small cell lung cancer (NSCLC). Intratumor injection of interferon-inducible protein 10 (IP-10, or CXCL10), an angiostatic CXC chemokine, led to reduced tumor growth in a SCID mouse model of NSCLC. In this study, we hypothesized that treatment with CXCL10 would, by restoring the angiostatic balance, improve long-term survival in NSCLC-bearing SCID mice. To test this hypothesis, A549 NSCLC cells were injected in the subcutis of the flank, followed by intratumor injections with CXCL10 continuously (group I), or for ten weeks (group II), or a control group (human serum albumin). Median survival was 169, 130, and 86 days respectively (P<0.0001). We extended these studies to examine the mechanism of prolonged survival in CXCL10-treated mice. CXCL10 treatment inhibited lung metastases, but was dependent upon continued treatment, and was associated with an increased rate of apoptosis in the primary tumor, with no direct effect on the proliferation of the NSCLC cells. Furthermore, the inhibition of lung metastases was due to the angiostatic effect of CXCL10 on the primary tumor, since the rate of apoptosis within lung metastases was unaffected. These data suggest that anti-angiogenic therapy of human lung cancer should be continued indefinitely to realize persistent benefit, and confirms the anti-metastatic capacity of localized angiostatic therapy. PMID- 11776376 TI - Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma. AB - For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA D227A-conjugated antibodies for targeted cancer immunotherapy. PMID- 11776377 TI - Tumor-specific targeting of a cell line with natural killer cell activity by asialoglycoprotein receptor gene transfer. AB - Targeting of immunological effector cells to tumor cells could be an efficient strategy of adoptive immunotherapy. The success of this strategy depends on the specificity of the effector cells and their availability in sufficient numbers. The aim of this study was to target the human natural killer cell line YT specifically to tumor cells. The cell line was modified by transfection with the cDNA of the human asialoglycoprotein receptor (ASGPR). This C-type lectin recognizes carbohydrates containing terminal galactosyl (Gal) residues, including the beta1-Gal bearing Thomsen-Friedenreich (TF) antigen, which is found on tumor cells. Binding assays revealed that the ASGPR-gene-transfected YT cell line binds significantly higher to tested target tumor cell lines than the mock-transfected control cells. Cytolytic activity against the tumor cell lines Raji, Jurkat and the TF-positive KG1 subline was increased. Genetic modification of YT cells could provide a useful tool for tumor targeting in immunotherapy. PMID- 11776378 TI - Generation and characterization of recombinant human antibodies specific for native laminin epitopes: potential application in cancer therapy. AB - Laminins are specific cellular regulators that directly and indirectly control activities such as cell attachment and migration, differentiation and polarity, proliferation and apoptosis, and protease expression. Considering the centrality of these issues to tumor progression, the generation of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti laminin antibody fragments. A library of single chain antibodies was selected using intact mouse laminin, and five different clones were identified. All the antibodies were specific for their cognate antigen, as revealed by lack of cross reactivity with other components of the basement membranes. A more extensive characterization of the panel indicated that these antibodies recognize the native protein through conformational epitopes. All of them reduced tumor cell attachment to laminin, suggesting that domains of the laminin molecule that are recognized by these antibodies likely bind to cell-surface receptors. The antibody fragments bind to mouse, rat and human laminin. and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications. PMID- 11776379 TI - T-helper (Th)1/Th2 imbalance in patients with previously untreated B-cell diffuse large cell lymphoma. AB - T-helper (Th)1/Th2 imbalance has been observed in a variety of pathological conditions, including malignant diseases. We evaluated the Th1/Th2 balance in peripheral blood Th cells by means of intracellular cytokine analysis in 19 patients with previously untreated B-cell diffuse large cell lymphoma (DLCL) and in 18 patients with B-cell DLCL who had achieved complete remission (CR) after chemotherapy. The mean percentage of Th2 in CD4 cells in patients with DLCL (5.00 +/- 2.20) and that of Th1 in CD4+ cells in patients in CR (32.42 +/- 11.30) were significantly increased in comparison with those in healthy volunteers, respectively (Th1; 23.02 +/- 9.45, Th2; 3.25 +/- 0.90; P<0.01). The mean ratio of Th1/Th2 was significantly lower in patients with DLCL (4.74 +/- 0.52) than in patients in CR (9.31 +/- 1.06; P<0.01) and in healthy volunteers (7.25 +/- 0.65; P<0.01). We conclude that the Th1/Th2 balance was polarized to Th2 in untreated DLCL patients and to Th1 in patients in CR, which suggests that a Th1/Th2 imbalance could play a role in lymphomagenesis and durable remission. PMID- 11776381 TI - Genetic polymorphisms in the promoter and 5' UTR region of the Fc alpha receptor (CD89) are not associated with a risk of IgA nephropathy. AB - The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc alpha receptor (FcalphaR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5'-untranslated region region of the FcalphaR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and T+56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcalphaR gene do not appear to be primarily involved in the susceptibility to IgAN. PMID- 11776380 TI - Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation. AB - A Polish family was identified in which multifocal clear cell renal carcinoma segregated with a balanced constitutional chromosome translocation, t(2:3)(q33;q21), similar to the renal cell cancer-associated t(2;3)(q35;q21) reported in a Dutch family. Bacterial artificial chromosome (BAC) contigs encompassing the 2q and 3q breakpoints were constructed and BACs crossing the breakpoints were partially sequenced. All known regional markers, genes, and expressed sequence tags (ESTs) were mapped relative to the contigs, as well as to the breakpoint sequences. Two single ESTs mapped within the 2q breakpoint BAC, whereas the repeat-rich 3q breakpoint region was gene poor. Physical mapping suggested that the 3q break was in 3q13, possibly near the border with 3q21. Physical mapping illustrated that the 2q break was closely telomeric to the 2q31 FRA2G site, consistent with the G-band assignment. Characterization of full length cDNAs for the ESTs near the 2q break will determine if a gene(s) is altered by this familial translocation. PMID- 11776382 TI - ABCC6 gene polymorphism associated with variation in plasma lipoproteins. AB - The ATP cassette-binding (ABC) gene superfamily contains more than 40 members, many of which are involved in cellular lipid transport. The most prominent example is ABCA1, mutations in which affect plasma high-density lipoprotein (HDL) cholesterol concentration. ABCC6 is another member of the ABC gene family, and mutations in ABCC6 were recently shown to cause pseudoxanthoma elasticum (PXE). A Canadian patient with PXE was referred for assessment of moderately severe type IV hyperlipoproteinemia with hypoalphalipoproteinemia, which was refractory to pharmacological treatment. We identified intron-exon boundaries of ABCC6 to sequence genomic DNA from this patient to find the disease mutation. We report (1) identification of a set of amplification primers for the 31 exons of ABCC6; (2) identification of the ABCC6 R>X1164 nonsense mutation in the PXE subject with dyslipidemia; (3) identification of common amino acid variants and silent nucleotide variants in ABCC6, with a range of allele frequencies across ethnic groups; (4) evidence consistent with a possible pseudogene encoding 9 exons with sequence homology to ABCC6; and (5) association of the ABCC6 R>Q1268 variant with plasma triglyceride and HDL cholesterol. The results suggest that ABCC6 may be a determinant of plasma lipoproteins. PMID- 11776383 TI - Identification of an aberrant type of rearrangement in the T-cell receptor alpha/delta locus in adult T-cell leukemia. AB - V(D)J recombination is the mechanism by which antigen receptor genes are assembled by three basic steps: cleavage, processing of broken DNA ends, and joining. In this process of recombination, the broken DNA molecules excised from different receptor gene loci are often joined to generate interlocus joints. The interlocus recombination process contributes to the translocation between antigen receptor genes and oncogenes, leading to the malignant transformation of lymphocytes. The alpha and delta chain of the T-cell receptor (TCR alpha/delta) locus at chromosome 14q11 is also a region where several types of chromosome translocations occur in T-cell malignancies. In the process of analyzing TCR alpha rearrangements in a patient with adult T-cell leukemia (ATL) carrying a translocation at chromosome 14q11, we found novel complex rearrangements in the Jalpha locus. On the one hand, the V2.3 gene is joined to the heptamernonamer recombination signal sequence of the J37 gene, and, on the other hand, the J37 gene is joined to the V2.3 recombination signal sequence through head-to-head fusion. These recombination products or hybrid joints originated through an inversion of about 70kb DNA. Interestingly, the inverted DNA stretch contains a normal V8.1-J40 rearrangement. These findings are the first direct demonstration that successive rearrangements with hybrid joints occur on the same chromosome in the human TCR alpha locus. PMID- 11776384 TI - Identification of nonsynonymous polymorphisms in the superantigen-coding region of IDDMK1,2 22 and a pilot study on the association between IDDMK1,2 22 and type 1 diabetes. AB - To investigate the possible involvement of IDDMK1,2 22/HERV-K18 in childhood type I diabetes mellitus, we identified two nonsynonymous A/G polymorphisms in the superantigen-coding region of IDDMK1,2 22 at the 290- and 461-nucleotide (nt) positions from the initial methionine codon and compared their frequencies in 74 Japanese patients with type 1 diabetes and in 54 nondiabetic controls. Although the G substitution was observed more frequently at either site in the patients than it was in the controls (7% vs. 4% at 290 nt, and 29% vs. 20% at 461 nt), the differences were not statistically significant. A weak significance of difference in the frequency of 461G was obtained only in an early-onset group of patients manifesting the disease at 5 years of age or less (n = 24) when compared with controls (38% vs. 20%; P = 0.03). However, in addition to the common absence of a particular allele among the expected four alleles, remarkable differences in allele frequencies were present between Japanese and European populations. This first trial investigating the association of IDDMK1,12 22 with type 1 diabetes presents intriguing suggestions for the role of this region in the etiology of autoimmune and infectious diseases. PMID- 11776385 TI - VNTR sequence on human chromosome 11p15 that affects transcriptional activity. AB - We found a variable number of tandem repeat (VNTR) sequence with 38-bp repetitive units in the promoter region of a gene of unknown function on human chromosome 11p15. Polymerase chain reaction amplification of this VNTR sequence using genomic DNA from 80 unrelated individuals revealed two common alleles, one with 10 (79% allelic frequency) and the other with 14 (14% allelic frequency) repetitive units, and two rare alleles with 22 (3%) or 30 (3%) repetitive units. We investigated whether differences in the length of this VNTR sequence would affect transcriptional activity of a heterologous promoter by transient transfection to NEC8, embryonal carcinoma cells derived from testis. The activity of the promoter was suppressed significantly when the VNTR region was cloned upstream, in a manner dependent on the number of repeats present in the VNTR sequence. The results implied that this polymorphic VNTR sequence might function as transcriptional regulator in 11p15, with differences in the number of repetitive units influencing efficiency of transcription of the gene lying downstream. PMID- 11776386 TI - Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions. AB - The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Dohle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan. Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity. PMID- 11776387 TI - Single-nucleotide polymorphisms of the proprotein convertase subtilisin/ kexin type 5 (PCSK5) gene. AB - The proprotein convertase. subtilisin/kexin type 5, or PCSK5, mediates post translational endoproteolytic processing for several integrin alpha subunits. We identified two silent single-nucleotide polymorphisms (SNPs) in PCSK5, which were found to vary in frequency across ethnic groups. The identification of these amplification primers and SNPs provides tools to investigate PCSK5 for association with inflammatory or vascular phenotypes. PMID- 11776389 TI - Eight single-nucleotide polymorphisms (SNPs) at the human tissue-type plasminogen activator (t-PA) locus. PMID- 11776388 TI - Heterozygous 17-bp deletion in the forkhead transcription factor gene, FOXL2, in a Japanese family with blepharophimosis-ptosis-epicanthus inversus syndrome. AB - We examined mutations in the forkhead transcription factor gene, FOXL2, in three members a Japanese family with autosomal dominant blepharophimosis-ptosis epicanthus inversus syndrome (BPES) and in 100 healthy controls. The FOXL2 was analyzed by direct genomic sequencing. A novel 17-bp deletion at nucleotides 1092 1108 in FOXL2 was found in the three affected patients. No mutation was found in any of the 100 healthy controls. The 17-bp deletion in FOXL2 may be involved in the pathogenesis of BPES in Japanese patients. PMID- 11776390 TI - From oocyte maturation to the in vitro cell cycle: the history of discoveries of Maturation-Promoting Factor (MPF) and Cytostatic Factor (CSF). AB - This article briefly reviews the classical cell cycle studies using oocytes and zygotes of mainly amphibians in the past century. The discussions are focused on the investigations into the cytoplasmic factors that regulate meiosis during oocyte maturation and the initiation of mitosis during fertilisation, which were carried out in the author's lab between 1967 and 1987. This chronicle traces the development of the problems and the direction in which their solutions were attempted in the course of these investigations. The author tries to answer the following questions: why he decided to study oocyte maturation, how he discovered progesterone as a maturation-inducing hormone, how he discovered and characterised the cytoplasmic regulators of the cell cycle, Maturation-Promoting Factor (MPF) and Cyto-Static Factor (CSF), and how he invented the method of observing cell cycle processes in a cytoplasmic extract in vitro. PMID- 11776391 TI - Replication timing and cell differentiation. AB - Cell differentiation may depend in part upon a type of unbalanced growth in which several cell cycles occur with a reduced level of total protein synthesis. During this period the synthesis of the chromatin protein HMG-I/Y is reduced since its synthesis is correlated with that of total protein. The synthesis of histone H1 shows less reduction since its synthesis is entrained with that of DNA. This greater reduction of HMG-I/Y than of histone H1 is thought to delay or prevent replicon initiations within AT-enriched isochores. This shifts their time of replication from early to late S phase. This may restrict certain pathways of cell differentiation in multipotent progenitor cells and allow one particular type of differentiation. PMID- 11776392 TI - Thyroid hormone-induced expression of sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine. AB - Sonic hedgehog (Shh) was isolated from the Xenopus laevis intestine as an early thyroid hormone (TH) response gene. To investigate possible roles of TH upregulated expression of Shh during metamorphosis, we raised a polyclonal antibody against Xenopus Shh and immunohistochemically examined the relationship between Shh expression and the larval-to-adult intestinal remodeling at the cellular level. Our results indicate that the epithelial-specific expression of Shh in the intestine spatiotemporally correlates well with active proliferation and/or initial differentiation of the secondary (adult) epithelial primordia that originate from stem cells, but not with apoptosis of the primary (larval) epithelium. Given the similar transformations of the stomach during metamorphosis, we also analyzed Shh expression in this organ and found similar correlations in the stomach, although the position of the adult epithelial primordia and their final differentiation in the stomach are different from those in the intestine. Furthermore, we show here that Shh expression is organ autonomously induced by TH and its correlation with the adult epithelial development is reproduced in vitro in both the intestine and the stomach. More importantly, addition of recombinant Shh protein to the culture medium results in developmental anomalies of both organs. However, differentiation of the adult epithelium is more severely inhibited by exogenous Shh in the intestine than in the stomach. These results suggest that TH-upregulated expression of Shh plays important roles in the postembryonic gastrointestinal remodeling, but its roles are at least partially different between the intestine and the stomach. PMID- 11776393 TI - Mesoderm-independent regulation of gastrulation movements by the src tyrosine kinase in Xenopus embryo. AB - In vitro studies have demonstrated the involvement of Src kinases in several aspects of cell scattering, including cell dissociation and motility. We have therefore sought to explore their functions in the context of the whole organism. Loss-of-function microinjection studies indicate that the ubiquitous Src, Fyn, and Yes tyrosine kinases are specifically implicated in Xenopus gastrulation movements. Injection of mRNAs coding for dominant negative forms of the ubiquitous members of the Src family, namely Fyn, Src, and Yes, perturbs gastrulation movements, resulting in the inability to close the blastopore. Injection of mRNA coding for Csk, a natural inhibitor of Src kinase activity, produces the same phenotypic alterations. The ubiquitous Src kinases have redundant functions in gastrulation movements since overexpression of one member of the family can compensate for the inhibition of another. Interfering mutants of the Src family also inhibit activin-induced morphogenetic movements of animal cap explants isolated from injected embryos. In contrast, these mutants do not interfere with mesoderm induction, as inferred from the presence of mesoderm derivatives and from the expression of early mesodermal markers in injected embryos. In addition, Src kinase activity measured by an in vitro kinase assay is elevated in gastrulating embryos and in FGF- and activin-treated animal caps, confirming the implication of Src enzymatic activity during gastrulation. Altogether, our results demonstrate that Src kinases are essential components of the machinery that drives gastrulation movements independent of mesoderm induction and suggest that Src activity is primarily implicated in cellular movements that take place during the process of cell intercalation. PMID- 11776394 TI - Expression of collagenase-3 (MMP-13) in c-fos-induced osteosarcomas and chondrosarcomas is restricted to a subset of cells of the osteo-/chondrogenic lineage. AB - The interstitial collagenases have been suggested to play a critical role in bone formation, remodeling, and cancerogenesis. We have previously shown that during mouse development expression of collagenase-3 (MMP-13) is restricted to bone and cartilage (Gack et al., 1995; Tuckermann et al., 2000) and is affected in mice with altered c-Fos and Cbfa-1 expression (Gack et al., 1994; Porte et al., 1999). In this study, using immunohistochemistry (IHC) and in situ hybridization (ISH) techniques, we have identified cells of the osteoblastic lineage to be the origin of strongly enhanced levels of MMP-13 transcripts in c-fos-induced osteosarcomas. Expression in these cells is further increased in c-fos/c-jun double transgenic mice and paralleled by Cbfa-1 expression. Similarly, in spontaneous and radiation induced osteosarcomas, both c-Fos and MMP-13 proteins are detectable, suggesting that overexpression of both genes is a characteristic feature of osteosarcomas of different origin. We also observed high levels of MMP-13 in c-Fos-induced chondrosarcomas. In osteoblast-like cells and in cells of late chondrocyte differentiation such as hypertrophic chondrocytes, high levels of MMP-13 transcripts were found. In contrast, in anaplastic areas of the tumors representing highly proliferating chondrocytes, no MMP-13 expression is detectable, suggesting that in addition to Fos/AP-1, bone-specific transcription factors are responsible for restricted expression of collagenase-3/MMP-13 in a specific subset of cells of bone and cartilage in physiology and pathology. PMID- 11776395 TI - Characterization of olfactory nerve abnormalities in Twirler mice. AB - The sense of smell is perceived by olfactory receptor neurons (ORN) present in the olfactory epithelium located in the posterosuperior aspect of the nasal cavity. The axons of these ORN migrate to the olfactory bulb (OB), forming a nervous layer on the outermost part of the bulb, and finally synapse in glomerular structures in the OB. The ORN are unique in that they are constantly being renewed throughout life. We characterized the defects in the nasal cavity and olfactory nervous supply of Twirler (Tw) mice by histological and immunohistochemical means. Tw homozygotes have previously been shown to present with midfacial abnormalities in the form of clefts of the lip and palate (Lyon, 1958; Gong et al., 2000). We found that in the Tw homozygotes, the OB was abnormally shaped, the skeletal framework underlying the OB was disrupted, and the morphology of the nasal cavity was altered with poorly defined nasal turbinates. Immunohistochemical staining with antibodies that marked nerves in general (PGP 9.5) and mature ORN (omp) in the olfactory epithelium at two different embryonic stages and in newborn mice revealed the stratification of the olfactory epithelium in Tw homozygotes, albeit slightly thinner compared to wildtype. A striking difference in the olfactory epithelium was the lack of differentiation of the ORN in Tw homozygotes and the reduced axonal input to the OB. In Tw homozygotes at 14.5 days of embryonic development, the presence of many mature ORN found randomly in the mesenchyme suggests the loss of olfactory pathfinding cues to the OB. It is believed that the lack of appropriate pathfinding cues observed in the Tw homozygotes was responsible for the OB not having the appropriate trophic effect on the development and maturation of the ORN as had been observed in partially bulbectomized animals. The defects in the Twirler may prove to be a valuable system to analyze problems in olfactory pathfinding and maturation. PMID- 11776396 TI - Angiotensin II stimulates alpha-skeletal actin expression in cadiomyocytes in vitro and in vivo in the absence of hypertension. AB - Using a specific alpha-skeletal actin antibody, we have previously shown, that during hypertension-associated cardiac hypertrophy in the rat, the expression of alpha-skeletal actin in the myocardium is increased, but maintains focal distribution, compared to normotensive animals. In the present study, we have investigated whether alpha-skeletal actin expression can be induced in the absence of hypertension. For this purpose, we have examined transgenic mice overexpressing angiotensinogen exclusively in the heart. These animals are characterized by high cardiac angiotensin II levels and cardiac hypertrophy accompanied or not by high blood pressure depending on their genetic background, i.e. presence of one or two renin genes. Alpha-skeletal actin levels were highly increased in transgenic compared to wild-type myocardium independently of the number of renin genes, indicating that angiotensin II can stimulate alpha skeletal actin expression in normotensive animals. Additional in vitro experiments using cultured mouse and rat cardiomyocytes showed that angiotension II not only increases alpha-skeletal actin expression but also induces an increase of its incorporation within II-bands compared to control cardiomyocytes. Angiotensin II increases also the expression of alpha-smooth muscle actin in sarcomeres of cardiomyocytes as well as in fibroblastic cells present within the culture. PMID- 11776397 TI - Specific antibody and immunoglobulin responses after intestinal colonization of germ-free piglets with non-pathogenic Escherichia coli O86. AB - Colonization of the gut with components of commensal microflora profoundly affects the development of the immune system. The aim of the present study was to investigate mucosal and systemic B cell responses during the first few days after intestinal association of colostrum-deprived piglets reared in germ-free (GF) conditions with non-pathogenic Escherichia coli O86. Specific intestinal anti-E. coli antibodies (Ab), among which IgA Ab prevailed, were found 4 days after colonization (72% of standard) and their amount decreased 11 days later reaching 22% of standard. In contrast to mucosal Ab, specific serum Ab remained at the level of GF animals at day 4 (less than 10% of standard) and markedly increased 15 days after colonization (156% of standard). In addition to the occurrence of specific Ab, increased amounts of total immunoglobulins (Ig) of all isotypes were detected in sera and intestinal washings. Using the ELISPOT method an increased number of IgM, IgG and IgA-secreting lymphocytes were found in spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP) in colonized animals as compared to GF piglets. Contrary to cells from these lymphatic organs, B cells from thymus were not affected by E. coli stimulation. Our results show that at the onset of intestinal colonization, non-pathogenic E. coli specifically and polyclonally stimulate the mucosal and systemic humoral immunity, but relatively soon after stimulation, mucosal-specific responses in gut decreases, indicating the possible beginning of inhibition mechanisms (oral tolerance). PMID- 11776398 TI - Antigenicity and predefined specificities of the multi-epitope vaccine in candidate consisting of neutralizing epitope and mutated epitopes suggested a new way against HIV-1 mutation. AB - A seven-amino acid epitope GPGRAFY located inside the V3 loop on envelope protein gp120 of HIV-1 is the principal neutralizing epitope (PNE), and a subset of anti V3 antibodies specific for this epitope show a broad range of neutralizing activity. But this epitope undergoes restricted mutation. In this study, three epitope peptides [C-(GPGRAFY)2, C-(GPGQTFY)2 and C-(GPGQAWY)2] that contain neutralizing epitope GPGRAFY and its two mutated epitope GPGQTFY and GPGQAWY, were synthesized and then conjugated to carrier protein KLH (keyhole limpet hemocyanin). the epitope-vaccines C-(GPGRAFY)2-KLH, C-(GPGQTFY)2-KLH and C (GPGQAWY)2-KLH induced high levels of antibodies to three V3 loop peptides that contain these epitopes respectively, and the antibody response induced by each epitope-vaccine showed predefined epitope-specific. When these three epitope peptides mixed together and conjugated to carrier protein, or conjugated to carrier protein separately and then mixed together, high levels of epitope specific antibodies which respectively recognized these epitopes on V3 loop peptide and both mutated peptides all can be induced by both of them. In blotting assay, these epitope-specific antibodies all recognized the neutralizing epitope and mutated epitopes on peptides respectively. In addition, the reactivity of the antibodies with whole gp120 molecule which contained the epitope GPGRAFY was tested. Only the GPGRAFY-epitope-specific antibodies but not the other antibodies recognized the gp120 molecule. These results provide experimental evidence that the candidate multi-epitope-vaccine containing neutralizing epitope and mutated epitopes may bring new hope against viral mutation resulting in HIV-1 immune evasion and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1 infection. PMID- 11776399 TI - The failure of oral tolerance induction is functionally coupled to the absence of T cells in Peyer's patches under germfree conditions. AB - Although intestinal bacterial flora has been thought to play a role in the induction of oral tolerance, the mechanism has yet to be elucidated. We therefore examined the bacterial flora-dependent acquisition of susceptibility to oral tolerance induction using a gnotobiotic murine model. Germ-free (GF) mice exhibited a significant shortage of T cells in the PPs in comparison to SPF mice. A recovery in the number of such T cells was accomplished in the gnotobiotic mice associated with Bifidobacterium infantis or Escherichia coli but not in the gnotobiotic mice with Clostridium perfringens or Staphylococcus aureus. To examine the susceptibility to oral tolerance induction, these mice were orally given ovalbumin (OVA) as a tolerogen and then injected i.p. with the Ag. The Ag specific IgG1 in the serum remained at a low level in both SPF and those gnotobiotic mice groups containing a sufficient number of T cells in the PPs. However, no such unresponsiveness in the Ab response was observed in GF or the other gnotobiotic mice groups containing only a few T cells in the tissues. Adoptive cell transfer analysis clearly showed that a sufficient number of T cells in the PPs is required for the induction of oral tolerance. Furthermore, the reduced expression of SLC (secondary lymphoid-tissue chemokine), which is responsible for T-cell migration to lymphoid organs, was observed in the PPs of GF mice, resulting in a shortage of T cells in the tissues. However, the reduced expression of SLC was restored even in the GF mice after conventionalization, thus suggesting that the failure of oral tolerance induction is functionally coupled to the innate absence of T cells under the GF condition. PMID- 11776400 TI - Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain. AB - Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and rheumatic diseases. We detected anti-topo I positive silicosis patients without any symptoms of autoimmune diseases. The correlation between anti-topo I autoantibody responses and HLA class II has been established. HLA-DRB1*1502; DQB1*0601 has been reported to be the most frequent anti-topo I associated haplotype among Japanese SSc patients. In this study, haplotype HLA-DR15; DQ6 was detected in all 4 anti-topo I positive Asian Japanese SSc patients randomly selected. Furthermore, HLA-DQB1*0402 was identified in 3 of 4 anti-topo I positive silicosis patients. These findings coincide with the results of a previous study, in which all 4 Japanese patients with anti-topo I had the DQB1*04 alleles, whereas no studies among Caucasian-Americans, African-Americans and Choctaw Indians found the involvement of DQB1*04. We investigated common features among various DQB 1 alleles. HLA-DQB I with a distinct characteristic is clearly involved in the anti-topo I response irrespective of ethnic groups, the main disease, or silica exposure. A common positioning of distinct amino acids, (i.e. positions 14, 30, 57 and 77 of the DQbeta1 domain are methionine, tyrosine, aspartic acid and threonine, respectively,) seems to be associated with anti-topo I response. The above-mentioned amino acid sequence is detected in alleles *0301, *0303, *0306, *0401, *0402, *0601 and *0602. PMID- 11776401 TI - Different expressions of Ly-49 receptors on mouse NK and NK T cells. AB - NK T cells are a unique T cell lineage and are reported to express Ly-49 molecules which are inhibitory receptors specific for class I molecules. In this study, we examined the expression of activation and inhibitory receptors on NK T cells in different organs of beta2-microgloblin knock out (beta2mKO), C57BL/6 (B6; H-2b), C57BL/10 (B10; H-2b) and B10.D2 (H-2d) mice. The low level expression of inhibitory receptors Ly-49A and G2 on NKT cells as well as NK cells, which are specific for Dd antigen, were observed in B10.D2 mice, but not in beta2mKO, B6, or B10 mice. The small percentage of inhibitory receptor Ly-49C positive NK and NKT cells, which is specific for Kb and Dd antigens, was observed in BMC, LMC and SC of B6, B10 and B10.D2 mice compared to beta2mKO mice. On the contrary, the large percentage of Ly-49C positive NK T cells was observed in thymocytes of B6, B10 and B10.D2 mice compared to beta2mKO mice. Interestingly, Ly-49D activation receptor was hardly detectable on NK T cells in any organs of the 4 strains of mice whereas it was clearly detectable on NK cells. These findings suggest that the unique characteristics of NK T cells may mediate regulatory function in MHC class I antigen-restricted immunity. PMID- 11776402 TI - Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse. AB - Monocyte chemoattractant protein (MCP)-1 is a chemotactic cytokine for monocytes, memoryT cells and dendritic cells (DC). However, the precise role of MCP-1 in a variety of immunological responses remains unclear. In the present study, we analyzed contact hypersensitivity (CHS) using human MCP-1 transgenic mice (hMCP 1Tgm) that constitutively produce high levels of hMCP-1 in the sera. Following 2,4-dinitrofluorobenzene (DNFB) sensitization, enhancement of CHS was demonstrated in Tgm as compared with that in non-Tgm. Anti-hMCP-1 antibodies significantly inhibited the CHS in Tgm. A prominent accumulation of B7-1+I-Ad+ Langerhans' cells (LC) bearing haptens was detected in draining lymph nodes (DLN) of Tgm 24 h after DNFB or fluorescein isothiocyanate (FITC) sensitization. Similar results were obtained with BALB/c mice administrated recombinant (r) hMCP 1. Langerhans' cells (LC) in the epidermal sheets of Tgm increased in size and expressed high levels of I-Ad and B7-1 12 h after FITC application compared with those of non-Tgm. After 18 h, the number of LC in the epidermis was reduced in Tgm. It was also shown that the B7-1 expression on LC of BALB/c mice was augmented after culture with rhMCP-1. These findings demonstrate that MCP-1 not only accelerates LC migration from epidermis into the DLN after sensitization with haptens but also up-regulates the I-Ad and B7-1 expressions, which results in the enhanced T cell activation and CHS. PMID- 11776403 TI - Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. AB - It is believed that the pathogenesis of dengue is generated by a deregulation of the immunological response. Dengue virus-infected monocytes/macrophages are likely to secrete monokines, which play a role in clinical features observed in patients with dengue haemorrhagic fever or dengue shock syndrome. This is a report on a study on 45 individuals presenting clinical and laboratory characteristics of dengue virus infection. During the acute phase of infection, immunophenotyping of peripheral mononuclear leukocytes was carried out in 19 patients and demonstrated a reduced frequency of CD2+ lymphocytes and their CD4+ and CD8+ subsets. Normal ratios were recovered during convalescence. Also, during the acute phase, mononuclear cells proliferated poorly in response to mitogens and dengue antigens as detected by incorporation of radiolabeled thymidine. During convalescence the lymphoproliferative response was re-established. In addition, the presence of circulating cytokines was investigated in the plasma of the same 45 patients. Concentrations of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and soluble tumor necrosis factor receptor (sTNF-Rp75) were found to be significantly elevated in patients when compared to normal controls. The increase in TNF-alpha was correlated with haemorrhagic manifestations and the increase in IL-10 with platelet decay. The data demonstrate that during the acute phase of dengue infection subsets of T lymphocytes are depressed in terms of both rate and function and provide evidence that circulating pro-inflammatory cytokines, such as TNF-alpha, are important in the pathogenesis and severity of dengue. IL-10 may be downregulating lymphocyte and platelet function. PMID- 11776404 TI - IL-1beta, IL-1Ra and sIL-1RII in the culture supernatants of PMN and PBMC and the serum levels in patients with inflammation and patients with cancer disease of the same location. AB - An inflammation or an other malignant process may create a microenvironment that modulates the production and activity of cytokines and their regulators. In the present study we compared the secretion of IL-1beta and its regulatory proteins: IL-IRa and sIL-1RII by PMN and PBMC derived from patients with inflammation and patients with cancer disease of the same location. We also examined the serum levels of these mediators in groups of patients. The results obtained revealed changes in the secretion of IL-1beta and IL-1Ra which are more characteristic of PMN and PBMC from cancer patients than of the cells from patients with inflammation. In contrast, the secretion of sIL-1RII is more characteristic of PMN and PBMC derived from patients with inflammation. Furthermore, PMN appear to play more significant role in the secretion of IL-1Ra into the circulation of cancer patients than PBMC. In contrast, PBMC affect to a large extent the secretion of IL-1beta and sIL-1RII into the circulation of patients with inflammation than PMN. Concluding, the secretion of IL-1beta and its regulatory proteins may depend on the type of immune cells and the type of the disease. PMID- 11776405 TI - Dexamethasone inhibits apoptosis of eosinophils isolated from hypereosinophilic patients. AB - Glucocorticoids reduce in vivo the number of eosinophils and are effective in treatment of blood and tissue hypereosinophilia. Dexamethasone is a synthetic glucocorticoid known to induce in vitro apoptosis of eosinophils of healthy donors, and apoptosis may be a mechanism induced by glucocorticoids to reduce eosinophilia. Here we confirm that dexamethasone exerts a pro-apoptotic effect on eosinophils isolated from healthy subjects but that dexamethasone is not always a pro-apoptotic agent towards eosinophils from hypereosinophilic patients. Implications of these results in the resistance of some patients to a treatment by glucocorticoids are discussed. PMID- 11776406 TI - Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000. AB - Laboratory and clinical reports about the pathogenesis of the carcinogenicity and allergenicity of chromium compounds published between 1985 and 2000 have been reviewed as a basis for consideration of the pathogenetic mechanisms involved. There is good evidence from the clinic and the laboratory that Cr[VI] is the ion responsible for most of the toxic actions, although much of the underlying molecular damage may be due to its intracellular reduction to the even more highly reactive and short-lived chemical species Cr[III] and Cr[V]. Exposure to Cr[VI] can result in various point mutations in DNA and to chromosomal damage, as well as to oxidative changes in proteins and to adduct formation. The relative importance of these effects of chromium ions and of the free oxidising radicals they may generate in the body in causing tumours and allergic sensitisation remain to be demonstrated. Biochemical studies of the DNA-damaging effects and of the pathogenesis of the allergic reactions to chromium ions have not kept up with advances in understanding of the molecular basis of the effects of other carcinogens and allergens. PMID- 11776407 TI - Effect of spironolactone on cisplatin-induced nephrotoxicity in rabbits. AB - The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day(-1)), oral doses of spironolactone (20.0 mg kg day(-1)) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P<0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four- and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spironolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spironolactone significantly (P<0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit. PMID- 11776409 TI - Role of iron-dextran on 7,12-dimethylbenz(a) anthracene-initiated and croton oil promoted cutaneous tumorigenesis in normal and pregnant mice. AB - Skin chemical carcinogenesis has been divided into the process of initiation, promotion and progression. Earlier, we showed the role of iron overload in the promotion stage of skin carcinogenesis. In this communication, we report that iron overload does not augment croton oil-mediated tumor promotion in 7,12 dimethylbenz(a)anthracene (DMBA)-initiated pregnant mice skin tumorigenesis. Virgin female Swiss mice were given 1 mg iron/mouse/day parenterally for 2 weeks to induce iron overload. After the last injection, a group of mice was left with male mice for 10 days. These animals showed an increase in cutaneous iron concentration as compared to normal mice. Papillomas were induced in mice skin by a single topical application of DMBA as initiator. A week after the initiation, promoting agent, croton oil was applied twice per week for 20 weeks. The appearance of the first tumor (papilloma), number of tumors/mouse and percentage incidence were recorded. When compared to the iron unloaded control and iron overload pregnant groups, the iron overload virgin animals showed an increased incidence of tumors. In iron overload virgin animals, tumors appeared earlier and also the numbers of tumors/mouse were significantly higher. However, in iron overload pregnant animals, diminished tumor incidence was observed and the numbers of tumors matched the result of normal pregnant animals. Our results show that iron overload in pregnant mice does not participate in the augmentation of DMBA- and croton oil-induced skin tumorigenesis. PMID- 11776408 TI - Preclinical evaluation of the cardiotoxicity of PK2: a novel HPMA copolymer doxorubicin-galactosamine conjugate antitumour agent. AB - PK2 is a polymeric anticancer conjugate composed of an N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer backbone and pendant doxorubicin (DOX) linked via a Gly-Phe-Leu-Gly peptide spacer. Additionally galactose residues are present to facilitate liver targeting. To justify clinical evaluation of PK2 it was necessary to determine its late cardiotoxicity compared to that of free DOX. A well standardised Sprague-Dawley rat model was used with either intravenous (i.v.) administration (4, 8 and 12 mg/kg DOX equivalent) or intraperitoneal (i.p.) administration (12, 18, 24 and 36 mg/kg DOX equivalent) of PK2. This variation in the route was due to the limited solubility of PK2 at higher doses. PK2 showed two to three times less acute toxicity (assessed by the maximum reduction in body weight in the first 2 weeks) than free DOX, and both compounds were less toxic when given i.p.. No animals given PK2 i.v. showed clinical signs of cardiotoxicity, the only toxicity seen was abnormal tooth growth (approximately 50% of the animals receiving 12 mg/kg, DOX equivalent). In contrast, several animals receiving free DOX (1-4 mg/kg) i.v. died due to cardiotoxicity in an approximately dose-related manner. All animals receiving free DOX (4 mg/kg) died by 12 weeks. Following i.p. administration of PKZ there were only two late deaths related to cardiotoxicity and these were in the 24 mg/kg DOX equivalent group. All animals receiving PK2 at the highest dose (36 mg/kg DOX equivalent) died within 4 weeks, cardiotoxicity was not the main contributing factor. In this study, PK2 displayed a approximately 5-fold reduction in cardiotoxicity relative to free DOX and this supported the progression of PK2 into early clinical investigation. PMID- 11776411 TI - An in vitro comparison of the cytotoxicity of sulphur mustard in melanoma and keratinocyte cell lines. AB - In vivo, the pigment producing melanocytes are the most susceptible cell type to sulphur mustard (HD) in the epidermal region of pig skin. It has been postulated that this is due to the melanogenic pathway producing a cytotoxic, free radical cascade within the melanocyte following HD poisoning, leading to cellular necrosis and subsequent inflammation. To test this hypothesis, the cytotoxicity of HD was tested in three human melanoma cell lines and compared to SVK-14 human keratinocytes, a cell line in which the response to HD has already been characterised. The results of both neutral red (NR) and gentian violet (GV) assays showed that all three melanoma cell lines, particularly the G361 line, were less susceptible to the toxic effects of HD than the SVK-14 keratinocyte cell line. Preliminary data indicate that the expression level of the DNA repair cofactor, proliferating cell nuclear antigen (PCNA), is up to 13-fold greater in the HD-resistant cell line G361 compared to the HD-sensitive SVK-14 cell line. The data point to the importance of DNA lesions in HD-induced cell death and to potential mechanisms associated with increased resistance to HD. A dose-response study was carried out to confirm the differences between these two cell lines. It was found that the G361 line is 5-fold more resistant to HD and 5.5-fold more resistant to the cytotoxic effects of H2O2 than the SVK-14 line, as determined by the MTT assay. The results suggest that differences in the relative efficiency of DNA repair processes may underlie these responses. Whilst the study indicates the limitations of using melanoma cell lines (in vitro) to model melanocyte responses to HD, analysis of the biochemical basis of the observed differences in sensitivity to HD could assist in the identification of novel therapeutic strategies against HD. PMID- 11776410 TI - Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: prevention by superoxide dismutase+catalase and vitamins E and C. AB - Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialdehyde (MDA) produced inside the cells. The MDA-thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts. PMID- 11776412 TI - Three case reports of the use of haemodiafiltration in the treatment of salicylate overdose. AB - Aspirin (acetylsalicylic acid) is widely available without prescription. Although self-poisoning is rare, if severe it may be life threatening. Haemodialysis has been recommended in severe cases when salicylate levels exceed 7.3 mmol l(-1). We describe three cases of severe salicylate poisoning, which were treated with continuous veno-venous haemodiafiltration (CVVHDF). All patients survived. The first case had already undergone haemodialysis before transfer to the ICU, where CVVHDF was commenced because salicylism persisted at 3 mmol l(-1). A small reduction in serum salicylate was noted. In the second case, serum salicylate decreased from 8.5 to 3.5 mmol l(-1) after 3 h of CVVHDF even though only minimal urine was produced. Our third case is a chronic overdose in whom serum salicylate decreased from 6.2 to 4 mmol l(-1) after 4 h and to 1.4 mmol l(-1) after a further 7 h. No bicarbonate was administered to this patient and elimination can only be attributed to CVVHDF and urinary clearance, which is known to be slow. We discuss the pathogenesis of severe salicylate toxicity and postulate that CVVHDF, which is widely used in the intensive care setting, may be a useful therapy in severely poisoned patients who are unstable and cannot undergo haemodialysis or in situations where haemodialysis is unavailable. PMID- 11776414 TI - Posttraumatic stress disorder in a general psychiatric inpatient population. AB - This study examined the incidence of traumatic experiences and prevalence of lifetime posttraumatic stress disorder (PTSD) in a sample of 141 general hospital psychiatric inpatients. Sixty-one percent of the patients reported at least one traumatic event during their lifetime and 28% met the formal DSM-III-R criteria for a lifetime diagnosis of PTSD. A high degree of comorbidity between PTSD and other psychiatric disorders was found, but PTSD was the incident disorder in at least 50% of cases. The experience of trauma and its associated complex patterns of symptomatology suggest that PTSD complicates the process of recovery from another disorder. PMID- 11776413 TI - Recent victimization in women and men with severe mental illness: prevalence and correlates. AB - The problem of violence against individuals with severe mental illness (SMI) has received relatively, little notice, despite several studies suggesting an exceptionally high prevalence of victimization in this population. This paper describes the results of an investigation of the prevalence and correlates of past year physical and sexual assault among a large sample of women and men with SMI drawn from inpatient and outpatient settings across 4 states. Results confirmed preliminary findings of a high prevalence of victimization in this population (with sexual abuse more prevalent for women and physical abuse more prevalent for men), and indicated the existence of a range of correlates of recent victimization, including demographic factors and living circumstances, history of childhood abuse, and psychiatric illness severity and substance abuse. The research and clinical implications of these findings are discussed. PMID- 11776415 TI - The relationship of sleep quality and posttraumatic stress to potential sleep disorders in sexual assault survivors with nightmares, insomnia, and PTSD. AB - Sleep quality and posttraumatic stress disorder (PTSD) were examined in 151 sexual assault survivors, 77% of whom had previously reported symptoms of sleep disordered breathing (SDB) or sleep movement disorders (SMD) or both. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Posttraumatic Stress Scale (PSS). High PSQI scores reflected extremely poor sleep quality and correlated with PSS scores. PSQI scores were greater in participants with potential SDB or SMD or both. PSQI or PSS scores coupled with body-mass index and use of antidepressants or anxiolytics predicted potential sleep disorders. The relationship between sleep and posttraumatic stress appears to be more complex than can be explained by the current PTSD paradigm; and, sleep breathing and sleep movement disorders may be associated with this complexity. PMID- 11776416 TI - Psychophysiological reactivity in female sexual abuse survivors. AB - This study examined psychophysiological reactivity in 37 female childhood sexual abuse (CSA) survivors. After assessment of posttraumatic stress disorder (PTSD), psychiatric comorbidity, and trauma history, we conducted a psychophysiological assessment of forehead muscle tension, electrodermal activity, and heart rate during a mental arithmetic task and4 script-driven imagery tasks (neutral, consensual sex, pleasant, and trauma). PTSD symptom severity correlated positively with psychophysiologic changes and negative emotions during the trauma imagery task. During mental arithmetic, PTSD symptom severity correlated negatively with autonomic changes and positively with negative emotions. These results extend earlier PTSD research showing trauma-specific increased psychophysiological reactivity related to CSA in women with PTSD. They further suggest a negative association between PTSD severity and autonomic reactions to mental arithmetic. PMID- 11776417 TI - Rape and physical violence: comparison of assault characteristics in older and younger adults in the National Women's Study. AB - This study compared characteristics of recently occurring assaults against younger adults (age 18-34 years) with those of distant-past assaults against older adults (age 55-89 years) when they were younger. Responses of a subset of participants in the National Women's Study were the source of data for this study. With the exception of perceived life threat during assault (more prevalent in younger women), assault characteristics did not vary greatly by age in terms of proportions reporting that they had seen the perpetrator before; the event was one in a series; they or the perpetrator were under the influence of a substance; they actually experienced injury; and they reported the assault to authorities. Consistent with previous research, younger women reported greater prevalences of assault than older women. PMID- 11776418 TI - The long-term mental health consequences of child sexual abuse: an exploratory study of the impact of multiple traumas in a sample of women. AB - The current study examined exposure to multiple traumas as mediators of the relationship between childhood sexual abuse and negative adult mental health outcomes. Participants were 174 women interviewed in the third wave of a longitudinal study of the consequences of child sexual abuse. Child sexual abuse victims reported a lifetime history of more exposure to various traumas and higher levels of mental health symptoms. Exposure to traumas in both childhood and adulthood other than child sexual abuse mediated the relationship between child sexual abuse and psychological distress in adulthood. There were also some significant direct effects for child sexual abuse on some outcome measures. Results point to the importance of understanding the interconnected nature of trauma exposure for some survivors. PMID- 11776419 TI - Relationships among alcohol use, hyperarousal, and marital abuse and violence in Vietnam veterans. AB - Alcohol use (frequency and quantity) and the hyperarousal feature of PTSD were examined in relation to male-perpetrated marital abuse and violence using data from 376 couples who participated in the National Vietnam Veterans Readjustment Study. Veteran's self-reported hyperarousal was significantly associated with partner's report of physical violence and psychological abuse toward her. Differential relationships were found between veteran's self reported drinking frequency and drinking quantity and the outcomes; of the two components, only the average quantity consumed per occasion was independently related to husband-to wife violence. Moreover, a complex interaction emerged between hyperarousal and the two dimensions of alcohol consumption in predicting violence, with the relationship between hyperarousal and violence varying as a function of both drinking frequency and drinking quantity. PMID- 11776420 TI - Consistency of self-reports of traumatic events in a population of Dutch peacekeepers: reason for optimism? AB - Doubts have been raised concerning the reliability and the validity of self reports of traumatic events. A correlation between the number of inconsistencies in self-reports and the level of PTSD symptoms has been found. We examine whether these results can be generalized to a population of 137 Dutch peacekeepers who took part in operation UNTAC (United Nations Transitional Authority in Cambodia). The peacekeepers completed a 16-item trauma checklist, 3 and 4 years after their return from UNTAC. The test-retest reliability of the trauma checklist was adequate. Inconsistencies were randomly divided over all respondents and all items and were not correlated with symptoms of PTSD. No increase in the number of reported events over time was found. Earlier findings raising doubts concerning the reliability and validity of self-report measures of exposure were not replicated in this sample of Dutch peacekeepers. PMID- 11776421 TI - A qualitative analysis of posttraumatic stress among Mexican victims of disaster. AB - In unstructured interviews, 24 Mexicans described survivors' responses to disasters in Guadalajara, Jalisco (n = 9), Homestead, Florida (n = 6), and Puerto Angel, Oaxaca (n = 9). This analysis assessed the extent to which symptom descriptions corresponded to the 17 criterion symptoms of PTSD. Nineteen participants (79%) mentioned from 1 to 9 criterion symptoms. Event-related distress, hypervigilance, recurrent recollections, and avoiding reminders were described most often. Only 3 criterion symptoms were never described. Twenty participants (83%) provided 109 separate expressions that could not be classified specifically as criterion symptoms. These phrases were sorted by 9 independent Mexican volunteers and cluster analyzed. Clusters composed of ataques de nervios, depression, lasting trauma, and somatic complaints provided the best description of the data. PMID- 11776422 TI - "Transcend": initial outcomes from a posttraumatic stress disorder/substance abuse treatment program. AB - This paper describes the development of a comprehensive treatment program for combat veterans diagnosed with posttraumatic stress disorder (PTSD) and substance abuse (SA). Outcome data are presented on 46 male patients who completed treatment between 1996 and 1998. The treatment approach, defined by a detailed manual, integrates elements of cognitive-behavioral skills training, constructivist theory approaches, SA relapse prevention strategies, and peer social support into a group-focused program. The Clinician-Administered PTSD Scale (CAPS) and the Addiction Severity Index (ASI) were used to assess treatment effectiveness at discharge and 6- and 12-month follow-up. Significant symptom changes revealed on CAPS and ASI scores at discharge and follow-up are analyzed. Discussion focuses on hypotheses regarding treatment effectiveness, study limitations, and suggestions for further research. PMID- 11776423 TI - Translating research findings to PTSD prevention: results of a randomized controlled pilot study. AB - Based on therapeutic studies revealing positive prognostic factors and on research findings revealing how trauma is processed, we developed the memory structuring intervention (MSI) in attempt to prevent posttraumatic stress disorder (PTSD). The MSI attempts to shift processing of traumatic memory from uncontrollable somatosensory and affective processes to more controlled linguistic and cognitive processes by providing patients organization, labeling, and causality. In a single-blind randomized-controlled pilot study, 17 traffic accident victims at risk for PTSD (heart rate >94 BPM) were assigned to two MSI or two supportive-listening control sessions. Three months later, MSI patients reported significantly less frequent intrusive, arousal, and total PTSD symptoms than controls. A replication study with a larger sample is underway. PMID- 11776424 TI - Effects of writing about rape: evaluating Pennebaker's paradigm with a severe trauma. AB - We examined the effect of disclosing to others an attempted or completed rape. Eighty-five undergraduate women who acknowledged attempted or completed rape wrote about their experience and read their narratives. In a 2 x 2 design, we examined the value of writing only factual information versus factual plus emotional information, and reading to oneself versus reading aloud to another woman. Before and 1-month after the task, symptoms of dysphoria, social anxiety and posttraumatic stress disorder were assessed. Greater detail and a moderate level of personalization in the description of the trauma were associated with decreased symptoms of dysphoria and social anxiety. Neither the nature of the writing task nor the presence of another woman predicted degree of symptom reduction. PMID- 11776425 TI - Cognitive functioning and the early development of PTSD. AB - Cross-sectional studies of chronic PTSD reveal deficits in verbal memory. We studied cognitive functioning and its relationship to current and subsequent PTSD severity during an early phase of trauma response. Thiry-eight participants with traumatic injuries and only posttrauma incident psychopathology were evaluated shortly after admission to a Level I Trauma Center Neuropsychological measures were obtained at baseline and assessment of PTSD and other psychiatric disorders was conducted at baseline and follow-up, 6 weeks later. Significant negative correlations were found for follow-up PTSD severity with delayed recall and retroactive interference. These relationships were not significant for and were independent of baseline PTSD severity. Relative deficits in select areas of verbal memory after a trauma may confer greater risk for developing PTSD. PMID- 11776426 TI - A relational perspective on PTSD in early childhood. AB - This paper describes the clinical and research evidence for the importance of the relational context of posttraumatic stress disorder in young children. We review 17 studies that simultaneously assessed parental and child functioning following trauma. In many studies, despite limitations, an association between undesirable parental/family variables and maladaptive child outcomes has been consistently found. We present a model of the parental/family variables as moderators and vicarious traumatic agents for symptoms in young children. Also, a Compound Model is proposed, with three distinctive patterns of the parent-child relationship that impact on posttraumatic symptomatology in young children. Implications for clinical practice and research directions are discussed. PMID- 11776427 TI - Forced displacement in Yugoslavia: a meta-analysis of psychological consequences and their moderators. AB - A meta-analysis was conducted to synthesize what is known about differences in mental health between refugees and nonrefugees from the former Yugoslavia. The analysis focused on moderating effects of a variety of enduring, contextual stressors. Results indicated that refugees suffer significantly more mental health impairment than nonrefugees. The psychological consequences of forced displacement were found to vary significantly as a function of chronic stressors (e.g., locus of displacement and type of accommodation in exile) and were also associated with otherfactors (e.g., degree of war exposure in the nondisplaced groups, participant age, and time of data collection as reflected in year of publication). Implications for the study of refugee mental health are discussed. PMID- 11776428 TI - Examination of predictors of severe violence in combat-exposed Vietnam veterans. AB - This study examined several proposed predictors of severe wartime violence in a randomly selected, nationally representative sample of 1,125 Vietnam veterans. Participation in severe acts of violence during wartime was reported by 7.6% of the sample. Disruptive behavior before the age of 15 and increased combat exposure were both significant predictors of severe wartime violence. Childhood contextual factors were indirectly related to severe wartime violence via prewar disruptive behavior. The classification rate of perpetrators of severe violence was comparable to rates from studies of less severe forms of violence. The implications of these results and suggestions for future research in this area are discussed. PMID- 11776429 TI - The childhood trauma questionnaire in a community sample: psychometric properties and normative data. AB - Interpretation of research on the prevalence and sequelae of childhood trauma has been hindered by the use of assessment instruments with unknown psychometric properties. Thus, we examined the psychometric properties of a new childhood trauma measure, the Childhood Trauma Questionnaire (CTQ). The CTQ has demonstrated strong psychometric properties in clinical samples; limited information exists on its psychometric properties in community samples. Therefore, we explored the factor structure and reliability of the CTQ in a community sample and calculated normative data. Consistent with previous literature, a 5-factor model best described the CTQ, with a hierarchical model also providing excellent fit. Additionally, the CTQ demonstrated acceptable internal consistency. Overall, our findings suggest that the CTQ is appropriate for use in a community sample. PMID- 11776430 TI - Does everyone have a name? Psychological distress and quality of life among child holocaust survivors with lost identity. AB - Knowing one's identity, name, and biological parents is considered essential to personality development and psychological well-being. This study assessed post traumatic stress disorder (PTSD) symptoms, subjective quality of life (QoL), psychological distress, and potency in a group of adults who were children during the Holocaust (child Holocaust survivors) and who did not know their true identity. Twenty-three such survivors were compared to 23 child Holocaust survivors who knew their identity. Results showed that survivors with lost identity had lower physical, psychological, and social QoL and higher somatization, depression, and anxiety scores than did survivors with known identity. The findings suggest that the psychological consequences of not knowing one's identity are long-lasting. PMID- 11776431 TI - Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2. AB - The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone. The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide. The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro. This proline-rich peptide is a subsequence of beta-casein. From the observed absence in the literature of any other highly significant sequence homologues, memnopeptide A can be assumed to arise from metabolic products of the fungus with direct incorporation of constituents of the nutrient medium. The formation of memnopeptide A suggests this may be a mechanism for storage of amines by the fungus. Memnopeptide A has weak antibacterial activity against gram-positive bacteria and effects half maximal activation of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) at a concentration of 12.5 microM. PMID- 11776432 TI - A facile and effective screening method for p21WAF1 promoter activators from microbial metabolites. AB - We have developed a novel p21WAF1 promoter activator screening system based on rapid and facile luciferase activity assay of a model cell system (H1299/tsp53 luc cells), a stable luciferase expression cell line established by transfecting H1299/tsp53 cells with a reporter gene construct pWWP-Luc-BSD. This plasmid was constructed by subcloning the 2.4 kb p21WAF1 promoter and a 2.6 kb of luciferase cDNA fragment activated by the p21WAF1 promoter into a pMAM2-BSD expression vector containing the blasticidin S deaminase gene (BSD). A BSD-resistant clone H1299/tsp53-luc#4, showing the highest response to p53 activation (by temperature shift from 37 degrees C to 32 degrees C) by luciferase production, was used for screening microbial culture broths. Among approximately 1200 screened samples, trichostatin A related compounds and a new compound, lucilactaene, were isolated. This provides an effective and facile screening system for p21WAF1 promoter activators which should be of considerable value in the rapid identification of new anticancer agents. PMID- 11776433 TI - Characterization of mutants defective in melanogenesis and a gene for tyrosinase of Streptomyces griseus. AB - Nitrosoguanidine-induced melanin-negative mutants of Streptomyces griseus were classified according to their ability to produce streptomycin and A-factor, and to form aerial mycelium. A large proportion of the mutants showed deficiency in either antibiotic production and morphological development or both, suggesting close regulatory correlation between melanogenesis and morphological and physiological differentiation. The tyrosinase-encoding mel operon of S. griseus was cloned and examined for its role in melanogenesis of this organism. As in other Streptomyces homologues, the operon consisted of two open reading frames, melC1 encoding the putative cofactor and melC2 encoding the tyrosinase. Regardless of the distinct sequence similarity, introduction of the operon on plasmids failed to confer melanin production in the melanin-negative mutants, and the disruption of melC2 barely affected the melanin productivity, which indicated the presence of another enzyme involved in the melanogenesis in S. griseus. On the other hand, mel on a high-copy-number plasmid caused precocious aerial mycelium formation in Streptomyces lividans TK21 suggesting a stimulatory role of tyrosinase in morphological development. PMID- 11776435 TI - New biotransformation products of nemadectins. AB - Selected nemadectins (formerly LL-F28249 series) have been fed to a panel of microorganisms with the aim of generating new derivatives. In addition to products resulting from the oxidation of the terminal methyl group (C-29), a unique phosphorylated nemadectin was isolated. The phosphate group was determined to be at C-23 by HMBC between phosphorus and H-23. Milbemycin or nemadectin derivatives with natural substituents involving the 23-hydroxyl group were hitherto unknown. PMID- 11776434 TI - Directed biosynthesis of new enniatins. AB - New cyclohexadepsipeptides of the enniatin type with potential anthelmintic properties were produced by two different strategies: 1. In vitro synthesis by use of the multienzyme enniatin synthetase, and 2. in vivo precursor feeding of enniatin producing strains Fusarium scirpi and Fusarium sambucinum. The compounds were analyzed by HPLC, various NMR measurements and mass spectrometry. The three N-methyl L-amino acid positions in the enniatin B molecule could be gradually replaced by other (N-methyl) L-amino acids, e.g. alanine, cysteine, threonine and serine. The latter two amino acids yield new enniatins with functional groups in the hydrophobic side chains. Similarly the three D-2-hydroxyisovalerate residues, present in all naturally occuring enniatins, could be substituted by D-2 hydroxybutyric acid and D-lactic acid. Despite its lower yield the in vitro synthesis has the advantage of a broader variety of products formed. PMID- 11776436 TI - L-2,5-dihydrophenylalanine, an inducer of cathepsin-dependent apoptosis in human promyelocytic leukemia cells (HL-60). AB - L-2,5-Dihydrophenylalanine (DHPA), a phenylalanine analogue, induced apoptosis in human promyelocytic leukemia cells (HL-60). This apoptosis was demonstrated by morphological changes of the cells, such as fragmentation of nuclei and chromatin condensation, and by some evidence found in biochemical analysis, such as DNA ladder and activation of caspase 3. The DHPA-induced apoptosis was prevented by a pan-caspase inhibitor, Z-VAD-fmk, and a cysteine protease inhibitor, E-64d, which inhibits calpains and cathepsin B and L. A calpain inhibitor, Z-LL-H, did not affect this apoptosis. A cathepsin B specific inhibitor, CA074-Me, prevented only chromatin condensation. However, E-64d and a cathepsin L specific inhibitor, Z FY(t-Bu)-dmk, protected the cells from both chromatin condensation and oligonucleosomal DNA fragmentation. As proceeding to the apoptotic process, the activities of both cathepsin B and L increased gradually. These results indicated that DHPA was an inducer of cathepsin-dependent apoptosis in HL-60 cells. PMID- 11776437 TI - A simple screening system for anti-HIV drugs: syncytium formation assay using T cell line tropic and macrophage tropic HIV env expressing cell lines- establishment and validation. AB - The first step in cellular entry of HIV involves binding of the viral envelope glycoprotein complex (gp120/gp41) to specific receptor molecules on the target cells. The cell-cell fusion (syncytium formation) between env expressing cells and CD4+ cells mimics the viral infection of the host cells. To search for anti HIV substances preventing this process, we constructed the recombinant cell lines, HeLa/CD4/Lac-Z and HeLa/T-env/Tat for T-cell tropic (HIV-1(NL4-3)) system, and HOS/CD4/CCR5/Lac-Z and HeLa/M-env/Tat for macrophage tropic (HIV-1(SF162)) system. When each pair of cells were co-incubated for 20 hours, the multinuclear giant cells (syncytia) were formed and beta-galactosidase was expressed. These systems are less biohazardous because no infectious virus particles are used. Their validity in screening for anti-HIV substances which inhibit syncytium formation was confirmed using various known HIV entry inhibitors. PMID- 11776438 TI - YUA001, a novel aldose reductase inhibitor isolated from alkalophilic Corynebacterium sp. YUA25. II. Chemical modification and biological activity. AB - A series of novel N-substituted tyramine (2-p-hydroxyphenylethylamine) derivatives (1 to approximately 11) were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (EC 1, 1, 1, 21). Of these compounds, N-2-p-hydroxyphenylethyl maleamic acid (10) exhibits the strongest aldose reductase inhibitory activity, which is 22 times more potent than that of YUA001. PMID- 11776439 TI - Quinolactacins A1 and A2, new acetylcholinesterase inhibitors from Penicillium citrinum. PMID- 11776440 TI - Chrolactomycin, a novel antitumor antibiotic produced by Streptomyces sp. PMID- 11776441 TI - New immunosuppressive activity of dykellic acid. PMID- 11776442 TI - Novel amidine conjugates of the ornithine moiety of the macrocyclic antifungal lipopeptidolactone FR901469. PMID- 11776443 TI - 14-(2 ',3 ',5 '-Trihydroxyphenyl)tetradecan-2-ol, a novel acetylcholinesterase inhibitor from Chrysosporium sp. PMID- 11776444 TI - Lucilactaene, a new cell cycle inhibitor in p53-transfected cancer cells, produced by a Fusarium sp. PMID- 11776445 TI - Tribulations and trials: the Holy Grail of medical progress. PMID- 11776446 TI - Monochromatic infrared irradiation (890 nm): effect of a multisource array upon conduction in the human median nerve. AB - OBJECTIVE: Antidromic conduction studies in the human median nerve were used to assess the neurophysiological effects of irradiation of the skin overlying the nerve using a novel treatment unit comprising a multisource monochromatic infrared diode array (Equilight, Denver, CO). MATERIALS AND METHODS: Healthy human volunteers (n = 40) were recruited and randomly allocated to one of four groups: control, placebo, or one of two treatment groups (1.7 and 4.0 J/cm2). After baseline recordings of negative peak latency (NPL) were completed on the nondominant arm, subjects were treated according to group allocation. Recordings were subsequently repeated at 5-min intervals over a 45-min period. RESULTS: Analysis of negative peak latency difference scores (ANOVA) demonstrated significant differences in NPL between groups and over time (p < 0.05). While in the control and placebo groups NPL values remained relatively stable, in the two treatment groups such values decreased marginally, with the greatest effects observed in the 4.0 J/cm2 group (e.g., at 5 min, differences in NPL [mean +/- SEM]: control group, 0.02+/-0.03 msec; treatment group 2, 4 J/cm2, -0.07+/-0.03 msec). Similar significant differences were observed in skin temperature; correlation analysis indicated a weak (but expected) positive linear relationship between skin temperature and nerve conduction velocity (r = 0.125). CONCLUSION: These results suggest that irradiation at the parameters and under the conditions used here produce a direct neurophysiological effect. The magnitude of such effects are in keeping with previous findings using single source arrays at higher radiant exposures or thermal effects of the treatment unit. PMID- 11776447 TI - Analysis of surface roughness of enamel and dentin after Er,Cr:YSGG laser irradiation. AB - OBJECTIVE: The purpose of this investigation was to compare the surface roughness of enamel and dentin following the Er,Cr:YSGG laser irradiation and acid etching. BACKGROUND DATA: Laser-roughened enamel or dentin surfaces have been expected to enhance restorative materials bond strength. MATERIALS AND METHODS: Er,Cr:YSGG laser irradiation was performed in one half of each polished enamel or dentin sample at 3 W (33.9 J/cm2, with air 70% and water 20%,) pulse energy for 6 sec. Then the other half was treated with 37% phosphoric acid for 30 sec. Surface roughness and morphological studies were performed. RESULTS: It was found that surface roughness was significantly increased with the laser system. Scanning electron microscopy analysis showed that irradiated surface produces a rough surface that was completely lacking of a smear layer; there was also no cracking of enamel or dentin. CONCLUSION: Er,Cr:YSGG laser irradiation could provide an effective and alternative method to the acid etch technique. PMID- 11776448 TI - Effect of NASA light-emitting diode irradiation on wound healing. AB - OBJECTIVE: The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. BACKGROUND DATA: Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. MATERIALS AND METHODS: In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. RESULTS: LED produced in vitro increases of cell growth of 140 200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. CONCLUSION: We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program. PMID- 11776449 TI - Preventive effect of tooth fracture by pulsed Nd:YAG laser irradiation with diamine silver fluoride solution. AB - OBJECTIVE: The purpose of the present study was to evaluate the preventive effect of pulsed Nd:YAG laser irradiation with 38% diamine silver fluoride [Ag(NH3)2F] solution for the fracture of endodontically treated teeth in vitro. BACKGROUND DATA: There have been no reports on the preventive effect of tooth fracture using Nd:YAG laser with Ag(NH3)2F solution. MATERIALS AND METHODS: Twenty-eight human extracted teeth were used in this study. The teeth were randomly classified into four groups: control group, where tooth surfaces were not submitted to any treatment; group 1, where tooth surfaces were coated with 38% Ag(NH3)2F solution; group 2, where tooth surfaces were coated with Ag(NH3)2F solution and irradiated by pulsed Nd:YAG laser for 2 sec; and group 3, where tooth surfaces were coated with Ag(NH3)2F solution and irradiated by pulsed Nd:YAG laser for 10 sec. After preparation, shear tests were performed and the maximum load for the fracture was measured. Results were analyzed using the Scheffe test, and difference at p < 0.05 was considered significant. RESULTS: The failure load for group 2 (mean, 182.5 kg) had the highest mean value and differed significantly from those for the control group (mean, 146.3 kg) and group 1 (mean, 147.1 kg; p < 0.05). The failure loads for groups 1 and 3 (mean, 150.0 kg) did not differ significantly from that for the control group (p > 0.05). CONCLUSION: The results show that the application of 38% Ag(NH3)2F solution followed by pulsed Nd:YAG laser irradiation for 2 sec is useful for prevention of tooth fracture at endodontically treated teeth. PMID- 11776450 TI - Clinical comparison between conventional suture and vaporization with carbon dioxide laser in rat's skin. AB - OBJECTIVE: This study compares wound healing efficiency on a rat's skin when the incision was closed with a conventional suture versus vaporized with a CO2 laser. MATERIALS AND METHODS: In this study, 24 rats were used, and two longitudinal incisions were made with a conventional scalpel in the dorsum of each rat. The left incision was sutured with nylon thread, and the right incision was closed by vaporization with a defocused CO2 laser in continuous mode with an 8-watt power density. Clinical photographs were taken immediately after the procedure, 24 h later, and after 3, 7, 14, and 21 days, documenting the healing of the incision. RESULTS: The results showed that there was an initial delay in wound repair in the vaporized incision as compared to the scalpel incision, but after 21 days, both incisions showed the same clinical characteristics. However, the vaporized incision showed no trauma of the tissue, as opposed to the sutured incision, and no hemorrhagic complications. CONCLUSION: These results suggest that the CO2 laser can eventually replace the use of sutures. PMID- 11776451 TI - Microleakage and nanoleakage: influence of laser in cavity preparation and dentin pretreatment. AB - OBJECTIVE: The purpose of this study was to verify if the application of the Nd:YAG laser following pretreatment of dentin with adhesive systems that were not light cured in class V cavities and were prepared with Er:YAG laser would promote better sealing of the gingival margins when compared to cavities prepared the conventional way. BACKGROUND DATA: Previous studies had shown that the pretreatment of dentin with laser irradiation after the application of an adhesive system is efficient in achieving higher shear bond and tensile bond strength. MATERIALS AND METHODS: Er:YAG laser (Kavo-Key, Germany) with 350 mJ, 4 Hz, and 116.7 J/cm2 was used for cavity preparation. The conventional preparation was made with diamond bur mounted in high-speed turbine. Dentin treatment was accomplished using an Nd:YAG laser (Pulse Master 1000, ADT. USA) at 60 mJ, 10 Hz, and 74.65/cm2 following application of the adhesive system. The cavities were stored with Single Bond/Z100 and Prime & Bond NT/TPH. Eighty bovine incisors were used, and class V preparations were done at buccal and lingual surfaces divided into eight groups: (1) Er:YAG preparation + Prime & Bond NT + TPH; (2) Er:YAG preparation + Single Bond + Z100; (3) Er:YAG preparation + Single Bond + Nd:YAG + Z100; (4) Er:YAG preparation + Prime & Bond NT + Nd:YAG + TPH; (5) conventional preparation + Prime & Bond NT + TPH; (6) conventional preparation + Single Bond + Z100; (7) conventional preparation + Single Bond + Nd:YAG + Z100; (8) conventional preparation + Prime & Bond NT + Nd:YAG + TPH. All specimens were thermocycled for 300 full cycles between 5 degrees C+/-2 degrees C and 55 degrees C+/-2 degrees C (dwell time of 30 sec), and stored in 50% silver nitrate solution for 24 h soaked in photodeveloping solution and exposed to fluorescent light for 6 h. After this procedure, the specimens were sectioned longitudinally in 3 portions and the extension of microleakage at the gingival wall was determined following a criteria ranging from 0 to 4 using scanning electron microscopy (SEM). The medium portion sectioned of each specimen was polished and prepared for nanoleakage avaliation by SEM. RESULTS: Kruskall-Wallis and Miller statistical tests determined that group 3 presented less microleakage and nanoleakage. CONCLUSION: Application of the Nd:YAG laser following pretreatment of dentin with adhesive Single Bond non-photocured Single Bond adhesive in cavities prepared with Er:YAG promote better sealing of the gingival margins. PMID- 11776452 TI - Laser literature watch. PMID- 11776453 TI - Chemical ecology of triatomine bugs: vectors of Chagas disease. AB - Knowledge of chemical ecology of haematophagous triatomine bugs (Hemiptera: Heteroptera: Reduviidae) could be of practical value because this polyphyletic subfamily includes species of medical importance, such as vectors of Trypanosoma cruzi Chagas (Kinetoplastida: Trypanosomatidae), the aetiological agent of Chagas disease. For particular species of Dipetalogaster, Panstrongylus, Rhodnius and Triatoma, therefore, we review information on exocrine glands and products, interpreting their apparent roles as semiochemicals in the aggregation, alarm, defence, host-finding and sexual behaviour of these Triatominae. PMID- 11776454 TI - Evidence for an impact on the incidence of canine leishmaniasis by the mass use of deltamethrin-impregnated dog collars in southern Italy. AB - Dogs are the domestic reservoir of Leishmania infantum Nicolle (Kinetoplastida: Trypanosomatidae), the agent of zoonotic human visceral leishmaniasis. In southern Europe, where canine leishmaniasis (CanL) is widespread due to L. infantum, killing seropositive dogs is considered unacceptable and drug treatment has low efficacy in preventing transmission. We made a field evaluation of the efficacy of deltamethrin dog collars in a CanL focus of southern Italy, Mount Vesuvius area of Campania region, where the vector is Phlebotomus perniciosus Newstead (Diptera: Psychodidae), by assessing their impact on the incidence of CanL in an intervention town, compared to that in dogs of control towns where no collars were fitted. During two consecutive transmission seasons, collars were fitted to 350 (1998) and 354 (1999) dogs from San Sebastiano al Vesuvio (70% of the canine population). Control dogs (371 and 264 in the 2 years, respectively) were from four towns of the same area. Before each transmission season, the CanL seroprevalence in the intervention and control towns was evaluated by cross sectional surveys and found to be similar (about 15% in 1998 and 10% in 1999, respectively). After each transmission period, incidence rates of seroconversions were determined in adult dogs that were serologically negative before the season under evaluation, and in puppies. After the 1998 season, 2.7% of the dogs in the intervention town seroconverted compared to 5.4% in the control towns (50% protection, P = 0.15). After the 1999 season, 3.5% of collared dogs seroconverted compared to 25.8% of control dogs (86% protection, P < 0.001). The increase in seroconversion rates recorded in control dogs suggests an increase in the Leishmania force of infection in the canine reservoir during the 1999 sandfly season, as supported by the concomitant increase of human cases in control towns and in the whole Campania region. Our results suggest that the impact of mass use of deltamethrin-impregnated dog collars on the incidence of CanL may be negligible during low transmission seasons, or probably in low endemic foci, but can be very strong when the force of transmission is high. PMID- 11776456 TI - Laboratory and field evaluation of insect repellents as larvicides against the mosquitoes Aedes albopictus and Anopheles albimanus. AB - Acute toxicity and persistence of three insect repellents, deet and two piperidines (AI3-35765 and AI3-37220), were evaluated against mosquito larvae of Aedes albopictus (Skuse) and Anopheles albimanus Wiedemann (Diptera: Culicidae) in the laboratory, and against natural populations of Ae. albopictus in the field. In laboratory studies, the LC50 values of the repellents for first instars ranged between 0.005 and 0.021% (Ae. albopictus) and between 0.01 and 0.014% (An. albimanus) and, for fourth instars, between 0.019 and 0.034% (Ae. albopictus) and between 0.015 and 0.024% (An. albimanus). A 0.1% concentration of deet caused 90 100% mortality in first-instar Ae. albopictus for 4 weeks, whereas AI3-35765 and AI3-37220 at the same concentration killed 95-100% of larvae for 12 weeks and 98 100% of larvae for 33 weeks post-treatment, respectively. Deet and AI3-35765 at 0.1 % concentration resulted in complete mortality of first-instar An. albimanus for 3 weeks post-treatment, whereas AI3-37220 resulted in 91-99% larval mortalities for 35 weeks post-treatment. A 0.1% concentration of A13-37220 provided 77-98% larval mortality for 20 weeks and 63-97% larval mortality for 12 weeks post-treatment, respectively, against fourth-instar Ae. albopictus and An. albimanus. In the field, in artificial containers, the reduction of Ae. albopictus larvae caused by deet, AI3-35765 and AI3-37220 was 88-95% for 3-4 weeks, 98-100% for 7 weeks, and 82-100% for 13 weeks post-treatment, respectively. In used tyres, the same concentration of the repellents resulted in 100% reduction of Ae. albopictus larvae for 2 weeks (deet), 4 weeks (AI3-35765) and 5 weeks (AI3-37220) post-treatment. In cemetery flower vases, Aedes spp. larvae were eliminated for 4 weeks (deet) and 6 weeks post-treatment by both A13 35765 and AI3-37220. These topical repellents (particularly AI3-37220) have good potential for development and use in the management of container-inhabiting mosquitoes because they deter oviposition and kill larvae. PMID- 11776455 TI - Phlebotomine sandflies and leishmaniasis risks in Colombian coffee plantations under two systems of cultivation. AB - The phlebotomine sandfly fauna of traditional (shaded) and intensified (unshaded) coffee plantations in Colombia was sampled by a variety of methods and the species composition and density under the two systems compared. Twenty species of Lutzomyia sandflies (Diptera: Psychodidae: Phlebotominae) were collected, of which eight were found only in the 'Coffee Axis' ('Eje Cafetero') of the departments of Caldas, Risaralda and Quindio, six were exclusive to the department of Norte de Santander and six occurred in both regions. Four species were collected only in traditional plantations and two exclusively in intensified ones. At least 13 species occurred in both plantation types. Fifteen species are opportunistic man-biters and eight are suspected vectors of leishmaniasis caused by Le. braziliensis, Le. panamensis or Le. mexicana. Seven species were collected inside houses and may be involved in intradomiciliary transmission of Leishmania. The dominant species in Norte de Santander was Lu. spinicrassa, which made up 93.8% of all the sandflies collected in this department. This species was absent from the Eje Cafetero and a number of others among the 15 recorded there might be responsible for Leishmania transmission in this region, including Lu. trapidoi, Lu. yuilli, Lu. gomezi, L. hartmanni and Lu. ovallesi. Sandfly population densities were significantly higher in traditional plantations than in intensified ones. Residents of traditional plantations were able to describe sandflies in significantly more detail than those of intensified plantations, based on seven basic characteristics related to the appearance and biting behaviour of the insects. PMID- 11776457 TI - Factors influencing the abundance of Japanese encephalitis vectors in ricefields in India--I. Abiotic. AB - Mosquitoes of the Culex vishnui subgroup (Diptera: Culicidae) are the most important vectors of Japanese encephalitis (JE) and ricefields are their most productive breeding sites in south India, where predominant species of this subgroup are Culex tritaeniorhynchus Giles, Cx. pseudovishnui Colless and Cx. vishnui Theobald sensu stricto. The relationship of 13 abiotic variables with the abundance of Cx. vishnui subgroup immatures was investigated in transplanted rice fields for 3 years (1991-94) covering three different crop seasons. The results from the multiple regression model suggested paddy height (- ve), water temperature (+ ve), dissolved oxygen (- ve), ammonia nitrogen (- ve) and nitrate nitrogen (+ ve) to be the best predictor variables associated with the immature abundance, nearly always consistent in their effects within and between seasons. Application of synthetic nitrogenous fertilizers to the rice fields was followed by a rise in concentration of ammonia nitrogen and a subsequent increase in nitrate nitrogen level in the rice field water, during which an increase in the density of larval instars was observed. PMID- 11776458 TI - Old World screwworm fly, Chrysomya bezziana, occurs as two geographical races. AB - A morphological and molecular analysis was undertaken with the objective of identifying markers for geographical populations of Old World screwworm flies, Chrysomya bezziana Villeneuve (Diptera: Calliphoridae). The morphological analysis involved 192 adult flies from 14 countries, and the molecular analysis involved 45 larvae or adults from 14 populations in 11 countries. Principal components and cluster analysis of 10 morphological characters indicated that flies from Papua New Guinea (PNG) were a distinct group and most similar to flies from nearby Asian islands (Java, Sabah). There was poor resolution of other geographical regions, but some support for clustering of flies from Africa or India. Cladistic analysis of mitochondrial DNA sequences gave strong support for recognizing two races of Old World screwworm, one from sub-Saharan Africa and the other from the Gulf region and Asia. This latter race could be further divided into two lineages, i.e. one from mainland Asia (from Iraq to the Malay Peninsula) and the other from two islands of PNG. PMID- 11776459 TI - Molecular individuality and adaptation of the tick Rhipicephalus appendiculatus in changed feeding environments. AB - The tick Rhipicephalus appendiculatus Neumann (Acari: Ixodidae) naturally infests many host species. However, the mechanisms that enable it to feed on such a wide range of hosts are unclear. One possibility is that a tick population maintains molecular (genotypic and/or phenotypic) diversity among individuals such that individuals vary in their competency in taking bloodmeals under different feeding conditions. As a first step in testing this hypothesis, we showed that the polymorphism of salivary gland proteins, previously demonstrated in unfed ticks, was maintained during feeding on guinea-pigs. We then compared feeding performance under standard laboratory rearing conditions: one instar (adults or nymphs) feeding on guinea-pigs, with three changed conditions: (1) two instars (adults and nymphs) feeding together on guinea-pigs; (2) one instar (adults or nymphs) feeding on hamsters; and (3) two instars (adults and nymphs) feeding together on hamsters. The mean engorged weight of adult females was significantly reduced under all changed conditions, indicating that most of the adult individuals were significantly challenged by the changed conditions. However, some individuals achieved successful engorgement, indicating competence to the changed condition, and demonstrating variation in adaptive ability among individuals. Engorged females produced egg masses positively correlated to the engorged weights. More interestingly, the correlation coefficient (R) increased when feeding condition was changed. This may lead to more efficient selection for population adaptation under the changed conditions. As the feeding success of ixodid ticks depends on the efficiency of the cocktail of immunomodulatory saliva, the relevance of the polymorphism of salivary gland proteins and host adaptation is discussed. PMID- 11776460 TI - Seasonal activity and spatial distribution of host-seeking adults of the tick Dermacentor variabilis. AB - The seasonal temporal and spatial distribution and emergence of overwintering and summer cohorts of host-seeking American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), adults were examined for 5 years in the Bluegrass region of Kentucky. Weekly drag cloth sampling was conducted from early March until late September 1992-1995 and early March until the end of May 1996. Overwintering adult cohorts became active in early to mid-April followed by bimodal host seeking activity each year, with the duration and intensity of the first activity period being related to the previous year's summer cohort activity. The first activity peak extended from mid-April through late May and the second activity peak occurred in July. All host-seeking activity ceased by early August, except in 1995, when activity ended on 22 August. Laboratory survival of adults, collected weekly during 1993-1996, was used to estimate the emergence of summer adult cohorts. Summer adult cohorts became active in late May or early June and overlapped with overwintering adult host-seeking activity. The termination of host-seeking activity in overwintering adults could not be determined using the methods employed in this study and is most likely to have continued for the entire season. Host-seeking adults displayed contagious distribution patterns along trails bordering ecotone habitats, as determined by fitting a negative binomial frequency distribution to weekly sampling data. These patterns did not vary from year to year. In addition, the location of D. variabilis activity did not change from year to year, which suggests that microhabitats within apparently homogeneous environments enhance adult survival and lead to 'hot spots' of tick activity despite the ability of vertebrate hosts to disperse D. variabilis populations more widely. These data better define our understanding of D. variabilis adult seasonal and spatial host-seeking activity, estimate for the first time the intensity of summer cohort host-seeking activity, and relate summer cohort activity with spring activity the following year. PMID- 11776461 TI - Morphology and structural organization of Gene's organ in Argas walkerae. AB - Electron microscopy revealed that Gene's organ in females of Argas walkerae Kaiser & Hoogstraal (Ixodida: Argasidae) is formed as a double-sac structure consisting of an outer epithelial and an inner cuticular sac. The latter emerges through the camerostomal aperture to the exterior in ovipositing ticks. The epithelial sac forms the corpus and the two blind-ending horns, which pass into the epithelium of the excretory duct of a gland at each side of Gene's organ and envelop the cuticular sac. Both excretory ducts open into the lumen between the epithelial and the cuticular sac. The cuticular sac is folded and consists of a fibrous endocuticula outwards towards the lumen between the epithelial and the cuticular sac and of a smooth epicuticula inwards. Parallel running grooves occur over the lateral epicuticular surface turning medially into cobble-stone pavement like rises. Tubuli pass through the cuticular sac ending in pores on the epicuticular surface and open into the lumen between the epithelial and the cuticular sac. Muscle fibres pass through the epithelial sac at the horn tips and are inserted to the cuticular sac. In ovipositing females, the glands are fully developed and the lumen between the epithelial and the cuticular sac is filled with an amorphous mass. PMID- 11776462 TI - A key to the adults of species of blowflies in southern Australia known or suspected to breed in carrion. AB - The reliable morphological identification of carrion-breeding blowflies is important ecologically, as well as for medical, veterinary and forensic reasons. To date, no comprehensive key has been available to make this possible for workers in southern Australia. An illustrated key is presented to the adults of all species of blowflies (Diptera: Calliphoridae) south of 30 degrees S known or suspected to breed in carrion (species exclusive to Queensland and/or the Northern Territory are excluded). PMID- 11776463 TI - Larviposition by nasopharyngeal bot fly parasites of Columbian black-tailed deer: a correction. AB - Previous reports of Cephenemyia jellisoni Townsend (Diptera: Oestridae) larvipositing onto the lips/lower muzzle of deer, with larvae invading via the mouth, are shown to be erroneous. Additional studies with deer models baited with CO2, 1-octen-3-ol and Deer Trail Scent, and muzzle and nostrils treated with insect adhesive, revealed that only C. apicata Bennett & Sabrosky larviposited onto the lips/lower muzzle; C. jellisoni, by contrast, larviposited into the nostrils. Larval depositions were associated with females of both species observed attacking models. Females of both species also were found stuck on adhesive-treated, baited models not attended by observers. During several seasons of exposure, such models received 89 C. jellisoni larvipositions into the nostrils and 87 C. apicata larvipositions onto the lips/lower muzzle. In laboratory experiments nearly all larvae of both species remained stuck in adhesive within 1 mm or less of where they were deposited. PMID- 11776464 TI - Population morphometric analysis of the tropicopolitan bug Triatoma rubrofasciata and relationships with old world species of Triatoma: evidence of New World ancestry. AB - Quantitative analysis of morphological characters of the head was used to reconstruct the evolutionary history of the tropicopolitan bug Triatoma rubrofasciata (De Geer) (Hemiptera: Reduviidae) and seven species of Old World Triatoma. Multivariate analysis demonstrates that T. rubrofasciata and the Old World species have a high degree of similarity with Nearctic Triatoma species, particularly T. rubida (Uhler). We interpret this to imply a common ancestry for these groups. Dissemination of T. rubrofasciata and subsequent derivation of the Old World species of Triatoma is deduced to have occurred over a period of not more than 350 years. PMID- 11776465 TI - Seasonal reproduction and host infestation rates for nycteribiids of the large bentwing bat. AB - Large numbers of the nycteribiid species Nycteribia parilis vicaria Maa, Penicillidia (Penicillidia) oceanica Bigot and Penicillidia (Penicillidia) Maa (Diptera: Nycteribiidae) were collected from the bat Miniopterus schreibersii Kuhl (Chiroptera: Vespertilionidae) during a study on this bat's population genetics conducted largely in southern Australia. Bats were trapped in all seasons and at a number of locations throughout the ranges of the nycteribiids. Nycteribia parilis vicaria was the most common species captured. Gravid females of the three species were trapped in spring and summer and gravid female P. (P.) oceanica and N. parilis vicaria were trapped in autumn. Newly emerged adults of P. (P.) oceanica and N. parilis vicaria were captured in spring and autumn. Nycteribiid loads for individual bats were low, and there was no direct evidence of a detrimental effect on bats. PMID- 11776466 TI - Stem cells and Differentiation. PMID- 11776467 TI - Signaling the tips: regulation of stem cell function in plants. PMID- 11776468 TI - The stem cells of early embryos. AB - Cells resident in an organism that possess the dual capacity for self-renewal and differentiation into a spectrum of subtypes are referred to as stem cells. In the past decade, basic research performed on stem cells has shed light on the molecular pathways operating in vivo which can be harnessed in vitro for the establishment of cell lines mirroring the stem cells in the organism. The attractiveness of stem cells as in vitro models of organotypic differentiation and their potential application in a clinical context holds great promise and is only beginning to be exploited. Stem cells can be broadly grouped into two categories based on their origin from either the embryonic or the adult. Only the early embryo possesses truly pluripotent cells that can give rise to all the cell types present in the embryo proper and adult. The adult, on the other hand, possesses specialized, tissue- or organ-specific stem cell types, which can give rise to the differentiated cell types of that specific organ and have in some instances been shown to transdifferentiate. However, no stem cell obtained from an adult organism has yet been shown to exhibit developmental potential matching the breadth of that of stem cells obtained from embryos. This review focuses on the different types of stem cells that are resident in early stage mammalian embryos, detailing their derivation and propagation in addition to highlighting their developmental potential and opportunities for future applications. PMID- 11776469 TI - Embryonic stem cell differentiation: the role of extracellular factors. AB - Embryonic stem (ES) cells have the capacity to self renew and to differentiate into cellular derivatives of the endodermal, ectodermal, and mesodermal lineages. Therefore, ES cells have been used to analyse the effects of exogenous factors on the developmental pattern during in vitro differentiation. By using an in vitro loss-of-function approach based on beta1 integrin-deficient ES cells, it was found that integrin-dependent mechanisms are involved in the regulation of Wnt-1 and BMP-4 expression. Antagonistic effects of the signalling molecules Wnt-1 and BMP-4, morphogens involved in early differentiation events, have been observed in vivo and in vitro: BMP-4 acts as a potent mesoderm inducer, whereas Wnt-1 plays a critical role in the determination of neuroectoderm. Here, we summarise data of ES cell-derived cardiac, myogenic, and neuronal differentiation of wild type and beta1 integrin-deficient ES cells. We present evidence that the interaction of cells with the extracellular matrix via integrins determines the expression of the signalling molecules BMP-4 and Wnt-1, resulting in the activation of the mesodermal and neuroectodermal lineage, respectively. The results support the idea that the influence of the extracellular 'niche' on the developmental fate of pluripotent stem cells is determined not only by soluble factors, but also by the extracellular matrix. PMID- 11776470 TI - Induction of embryonic hematopoietic and endothelial stem/progenitor cells by hedgehog-mediated signals. AB - Blood and vascular endothelial cells form in all vertebrates during gastrulation, a process in which the mesoderm of the embryo is induced and then patterned by molecules whose identity is still largely unknown. Blood islands' of primitive hematopoietic cell clusters surrounded by a layer of endothelial cells form in the yolk sac, external to the developing embryo proper. These lineages arise from a layer of extraembryonic mesoderm that is closely apposed with a layer of primitive (visceral) endoderm. Despite the identification of genes such as Flk1, SCL/tal-1, Cbfa2/Runx1/AML1 and CD34 that are expressed during the induction of primitive hematopoiesis and vasculogenesis, the early molecular and cellular events involved in these processes are not well understood. Recent work has demonstrated that extracellular signals secreted by visceral endoderm surrounding the embryo are essential for the initiation of these events. A member of the Hedgehog family of signaling molecules (Indian hedgehog) is produced by visceral endoderm, can induce formation of blood and endothelial cells in explant cultures and can reprogram prospective neurectoderm along hematopoietic and endothelial cell lineages. Hedgehog proteins also stimulate proliferation of definitive hematopoietic stem/progenitor cells. These findings may have important implications for regulating hematopoiesis and vascular development for therapeutic purposes in humans and for the development of new sources of stem cells for transplantation and gene therapy. PMID- 11776471 TI - Common origins of blood and blood vessels in adults? AB - After embryonic development, the vast majority of cells are differentiated and all organs are in place. Growth of the organism then ensues and continues until adulthood, whereupon cell division largely ceases. In some tissues, notably the bone marrow, skin, and gut, cell proliferation continues throughout life to replace cells lost by attrition. This regeneration is fueled by rare, long-lived, and largely quiescent stem cells that give rise to committed progenitors, which in turn generate large numbers of fully differentiated cells. Mounting evidence suggests that such cells can significantly contribute to tissue repair and regeneration in adults and may therefore prove beneficial for autologous cell and gene therapies. This review focuses on the potential of adult stem cells to give rise to hematopoietic and vascular cells. We discuss evidence that a highly purified population of adult stem cells, termed SP cells, serves as a hematopoietic progenitor and can contribute to vascular regeneration after injury. We also discuss the potential relationship of these cells to the embryonic hemangioblast. PMID- 11776472 TI - The skeletal muscle satellite cell: stem cell or son of stem cell? AB - The concept of the adult tissue stem cell is fundamental to models of persistent renewal in functionally post-mitotic tissues. Although relatively ignored by stem cell biology, skeletal muscle is a prime example of an adult tissue that can generate terminally differentiated cells uniquely specialized to carry out tissue specific functions. This capacity is attributed to satellite cells, a population of undifferentiated, quiescent precursors that become activated to divide and differentiate in response to the demands of growth or damage. The aim of this review is to discuss the role of the satellite cell as an adult tissue-specific stem cell. We examine evidence for the presence of behaviourally and phenotypically distinct subpopulations of precursor within the satellite cell pool. Further, we speculate on the possible identity, origins and relevance of multipotent muscle stem cells, a population with both myogenic and hematopoietic potentials that has been isolated from whole muscle. Taken together, current evidence suggests the possibility that the regenerative compartment of adult skeletal muscle may conform to an archetypal stem cell-based hierarchy, maintained within a stem cell niche. It therefore remains to be seen whether all satellite cells are skeletal muscle-specific stem cells, or whether some or all are the progeny of an as yet unidentified muscle stem cell. PMID- 11776473 TI - In-vitro differentiation of pancreatic beta-cells. AB - Stem cell biology is a new field that holds promise for in-vitro mass production of pancreatic beta-cells, which are responsible for insulin synthesis, storage, and release. Lack or defect of insulin produces diabetes mellitus, a devastating disease suffered by 150 million people in the world. Transplantation of insulin producing cells could be a cure for type 1 and some cases of type 2 diabetes, however this procedure is limited by the scarcity of material. Obtaining pancreatic beta-cells from embryonic stem cells would overcome this problem. We have derived insulin-producing cells from mouse embryonic stem cells by a 3-step in-vitro differentiation method consisting of directed differentiation, cell lineage selection, and maturation. These insulin-producing cells normalize blood glucose when transplanted into streptozotocin-diabetic mice. Strategies to increase islet precursor cells from embryonic stem cells include the expression of relevant transcription factors (Pdx1, Ngn3, Isl-1, etc), together with the use of extracellular factors. Once a high enough proportion of islet precursors has been obtained there is a need for cell-lineage selection in order to purify the desired cell population. For this purpose, we designed a cell-trapping method based on a chimeric gene that fuses the human insulin gene regulatory region with the structural gene that confers resistance to neomycin. When incorporated into embryonic stem cells, this fusion gene will generate neomycin resistance in those cells that initiate the synthesis of insulin. Not only embryonic, but also adult stem cells are potential sources for insulin-containing cells. Duct cells from the adult pancreas are committed to differentiate into the four islet cell types; other possibilities may include nestin-positive cells from islets and adult pluripotent stem cells from other origins. Whilst the former are committed to be islet cells but have a reduced capacity to expand, the latter are more pluripotent and more expandable, but a longer pathway separates them from the insulin-producing stage. The aim of this review is to discuss the different strategies that may be followed to in-vitro differentiate pancreatic beta-cells from stem cells. PMID- 11776474 TI - Pluripotential stem cells derived from migrating primordial germ cells. AB - Pluripotent stem cells termed embryonic germ cells (EGCs) have earlier been derived from pre- and post-migrating mouse primordial germ cells (PGCs). We have recently obtained four EGC lines from migrating PGCs of 9.5 days post coitum (dpc) embryos. All lines were male with normal karyotype and showed properties that are similar to previously established EGC lines, including colony morphology, expression of alkaline phosphatase (AP), and expression of SSEA-1 antigen. The developmental potency of two of these lines was tested in vivo. They contributed to a range of tissues in fetal chimeras including heart, lung, kidney, intestine, muscle, brain and skin. We also examined the methylation status of the imprinted genes: Igf2r, p57Kip2, Lit1, H19 and Igf2. Igf2r, p57Kip2 and Lit1 were unmethylated in all analysed EGC lines, whereas H19 and Igf2 showed significant hypo-methylation in the 9.5 dpc EGC-1 line when compared to previously derived 11.5 dpc male EGC lines. This suggests that imprint erasure in the male germ line occurs prior to 9.5 dpc for all imprinted genes examined. PMID- 11776475 TI - The regulation of embryonic stem cell differentiation by leukaemia inhibitory factor (LIF). AB - LIF (leukaemia inhibitory factor) is commonly used to maintain mouse embryonic stem cells in an undifferentiated state. These cells spontaneously differentiate when allowed to aggregate in the absence of LIF, forming embryoid bodies in which early embryonic cell lineages develop. Using embryoid bodies cultured in the presence and absence of LIF, we show that although LIF inhibited the development of visceral and parietal endodermal cells, it did not affect the differentiation of the primitive endodermal cell precursors of these extraembryonic cell lineages. Furthermore, deposition of the basement membrane produced by the primitive endodermal cells, which separates them from the remaining cells of the embryoid body, still occurred. The differentiation of primitive ectodermal cells and their progeny was inhibited by LIF, as evidenced by the lack of expression of FGF-5, muscle, and neuronal markers. However, cavitation of the embryoid body and maintenance of the cells in contact with the primitive endodermal basement membrane as an epiblast epithelium still occurred normally in the presence of LIF. These results indicate that cavitation and formation of the epiblast epithelium are regulated by mechanisms distinct from those controlling the differentiation of epiblast cell lineages. Furthermore, although epithelium formation and cavitation do not require the differentiation of visceral endodermal cells, the results are consistent with the hypothesis that the primitive endodermal basement membrane is sufficient to induce the epithelialization of undifferentiated embryonic stem cells necessary for cavitation. PMID- 11776476 TI - Brain from bone: efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent. AB - Bone marrow stromal cells are able to differentiate into adipogenic, chondrogenic, myogenic, osteogenic, and cardiomyogenic lineages, all of which are limited to a mesoderm-derived origin. In this study, we showed that neurons, which are of an ectoderm-origin, could be generated from marrow-derived stromal cells by specific inducers, fibronectin/ornithine coating, and neurosphere formation. The neurons generated from marrow stroma formed neurites, expressed neuron-specific markers and genes, and started to respond to depolarizing stimuli as functional mature neurons. Among stromal cells, isolated mature osteoblasts which had strong in vivo osteogenic activity could be efficiently converted into functional neurons. This transdifferentiation or meta-differentiation was enhanced by Noggin, an inhibitor of bone morphogenetic proteins, in comparison with 5-azacytidine, a demethylating agent capable of altering the gene expression pattern. Marrow stroma is therefore a potential source of cells for neural cell transplantation. PMID- 11776477 TI - Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. AB - Muscle satellite cells are believed to represent a committed stem cell population that is responsible for the postnatal growth and regeneration of skeletal muscle. However, the observation that cultured myoblasts differentiate into osteocytes or adipocytes following treatment with bone morphogenetic proteins (BMPs) or adipogenic inducers, respectively, suggests some degree of plasticity within the mesenchymal lineage. To further investigate this phenomenon, we explore the osteogenic and adipogenic potential of satellite cells isolated from adult mice. Our experiments clearly demonstrate that satellite cell-derived primary myoblasts, expressing myogenic markers such as MyoD, Myf5, Pax7 and desmin, differentiated only into osteocytes or adipocytes following treatment with BMPs or adipogenic inducers, respectively However, satellite cells on isolated muscle fibers cultured in Matrigel readily differentiated into myocytes as well as osteogenic and adipogenic lineages, whereas primary myoblasts did not. Satellite cell-derived primary myoblasts isolated from mice lacking the myogenic transcription factor MyoD (MyoD-/-) differentiate into myocytes poorly in vivo and in vitro (Megeney et al., Genes Dev. 1996; Sabourin et. al, J. Cell Biol., 1999). Therefore, we tested whether MyoD-/- primary myoblasts display increased plasticity relative to wild type cells. Unexpectedly, the osteogenic or adipogenic differentiation potential of MyoD-/- primary myoblasts did not increase compared to wild-type cells. Taken together, these results strongly suggest that muscle satellite cells possess multipotential mesenchymal stem cell activity and are capable of forming osteocytes and adipocytes as well as myocytes. PMID- 11776478 TI - Genomic expression analysis implicates Wnt signaling pathway and extracellular matrix alterations in hepatic specification and differentiation of murine hepatic stem cells. AB - HBC-3 hepatic stem cells maintained in the undifferentiated state can be induced to differentiate along the hepatocyte lineage in response to DMSO (Rogler, 1997). In order to understand the complex transcriptional regulatory mechanisms associated with the differentiation of these somatic stem cells and to identify novel candidate stem cell and differentiation associated genes, we have begun to characterize the transcriptome of HBC-3 cells during a 7-day differentiation protocol. This analysis showed that differentiating HBC-3 cells undergo biphasic bursts of gene regulation peaking at 3 hours and 120 hours of DMSO treatment. In the undifferentiated state, HBC-3 cells express muscle, neuron, myeloid, and lymphoid specific genes that are rapidly downregulated during hepatocytic differentiation. Cluster analysis has revealed large groups of genes with different temporal regulation profiles demonstrating complex and widespread transcriptional changes. Specifically, we discovered a multifaceted downregulation of the Wnt/beta-catenin pathway accompanied by the repression of TCF target genes during HBC-3 differentiation. In addition, there is downregulation of cellular receptors for fibronectin and laminin and other extracellular matrix molecules indicative of widespread cell surface alterations. DMSO induces cell cycle arrest, and this is reflected in upregulation of growth inhibitory proteins such as cyclin I and p18 and downregulation of cyclins B1 and D. Genes needed for hepatocytic functions, such as apolipoprotein C-IV, phosphoenolpyruvate carboxykinase, alcohol dehydrogenase, and asialoglycoprotein receptor were upregulated. Finally, transcriptional regulators including Twist, Snail, HNF1a, and GATA6 were upregulated during differentiation of HBC-3 cells. The significance of these findings is that our genome-based approach has allowed the parallel identification of multiple regulatory pathways that is needed to begin to fully understand the complex differentiation process. PMID- 11776479 TI - Cell differentiation lineage in the prostate. AB - Prostatic epithelium consists mainly of luminal and basal cells, which are presumed to differentiate from common progenitor/stem cells. We hypothesize that progenitor/stem cells are highly concentrated in the embryonic urogenital sinus epithelium from which prostatic epithelial buds develop. We further hypothesize that these epithelial progenitor/stem cells are also present within the basal compartment of adult prostatic epithelium and that the spectrum of differentiation markers of embryonic and adult progenitor/stem cells will be similar. The present study demonstrates that the majority of cells in embryonic urogenital sinus epithelium and developing prostatic epithelium (rat, mouse, and human) co-expressed luminal cytokeratins 8 and 18 (CK8, CK18), the basal cell cytokeratins (CK14, CK5), p63, and the so-called transitional or intermediate cell markers, cytokeratin 19 (CK19) and glutathione-S-transferase-pi (GSTpi). The majority of luminal cells in adult rodent and human prostates only expressed luminal markers (CK8, CK18), while the basal epithelial cell compartment contained several distinct subpopulations. In the adult prostate, the predominant basal epithelial subpopulation expressed the classical basal cell markers (CK5, CK14, p63) as well as CK19 and GSTpi. However, a small fraction of adult prostatic basal epithelial cells co-expressed the full spectrum of basal and luminal epithelial cell markers (CK5, CK14, CK8, CK18, CK19, p63, GSTpi). This adult prostatic basal epithelial cell subpopulation, thus, exhibited a cell differentiation marker profile similar to that expressed in embryonic urogenital sinus epithelium. These rare adult prostatic basal epithelial cells are proposed to be the progenitor/stem cell population. Thus, we propose that at all stages (embryonic to adult) prostatic epithelial progenitor/stem cells maintain a differentiation marker profile similar to that of the original embryonic progenitor of the prostate, namely urogenital sinus epithelium. Adult progenitor/stem cells co-express both luminal cell, basal cell, and intermediate cell markers. These progenitor/stem cells differentiate into mature luminal cells by maintaining CK8 and CK18, and losing all other makers. Progenitor/stem cells also give rise to mature basal cells by maintaining CK5, CK14, p63, CK19, and GSTpi and losing K8 and K18. Thus, adult prostate basal and luminal cells are proposed to be derived from a common pleuripotent progenitor/stem cell in the basal compartment that maintains its embryonic profile of differentiation markers from embryonic to adult stages. PMID- 11776480 TI - New perspectives on acetaminophen and alcohol use. PMID- 11776481 TI - Acetaminophen use in patients who drink alcohol: current study evidence. AB - Package labeling for all over-the-counter pain relievers and fever reducers warns patients who drink 3 or more alcoholic beverages daily to consult with a physician before using these products. In the absence of accurate, consistent data, physicians have relied on retrospective and anecdotal evidence, which has perhaps led to greater restrictions on acetaminophen use than necessary for patients who consume alcohol. Recently, a well-controlled clinical study was conducted to more rigorously characterize the risk to alcohol users taking acetaminophen. In this randomized, double-blind, placebo-controlled trial, patients enrolled in a drug detoxification facility received 1000 mg acetaminophen or placebo 4 times daily for 2 consecutive days immediately after discontinuing alcohol use. Serum aspartate aminotransferase and alanine aminotransferase levels, used to detect hepatic necrosis or liver disease, were monitored at baseline and again both during and after the study. Results for 201 patients completing the study showed no statistically significant difference in liver function tests for 102 patients receiving acetaminophen compared with 99 patients receiving placebo. Researchers concluded that there was no increase in liver toxicity among alcoholic patients given the maximal therapeutic dose (4 g/day) of acetaminophen and no clinical evidence of increased risk for these patients when acetaminophen is used within recommended doses. PMID- 11776482 TI - The use and effect of analgesics in patients who regularly drink alcohol. AB - Analgesic consumption poses special risks for regular users of alcohol. Among the numerous adverse health effects are acetaminophen toxicity and gastrointestinal (GI) bleeding associated with nonsteroidal anti-inflammatory drug (NSAID) use. An alcohol-acetaminophen hypothesis contends that alcohol enhances acetaminophen toxicity. Because 22% of adults use acetaminophen each week and 5% to 10% of the population is alcoholic, the healthcare implications of serious adverse interactions are considerable. However, such interactions are rare when NSAID doses remain in the therapeutic range. Although clinical studies fail to support anecdotal case reports of liver damage associated with consumption of therapeutic doses of acetaminophen by alcohol users, such reports are probably inaccurate because of the uncritical acceptance of patient history by the clinician and a lack of well-designed prospective trials. Over-the-counter (OTC) NSAIDs, such as aspirin, naproxen, and ketoprofen, are other analgesic options, but each carries the risk of GI bleeding. Unanswered questions about the newer "second-generation" NSAIDs, such as celecoxib and rofecoxib, make them less desirable than acetaminophen and OTC NSAIDs. Because the risk of GI bleeding or ulceration may be higher in alcoholic patients, the optimal strategy in prescribing pain relievers to those who consume alcohol is to use 1 drug at a time and to clearly communicate its generic name. Acetaminophen is the safest OTC analgesic and is recommended as first-line treatment for osteoarthritis. OTC NSAID users should be carefully advised as to recommended dose, and all patients should be reminded to stay within the dosing limits regardless which OTC analgesic is used. PMID- 11776483 TI - Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas: great logic, grim reality. PMID- 11776484 TI - Does the tumor status of the regional lymph nodes really matter in melanoma? PMID- 11776485 TI - Is an FDG-PET scan the new imaging standard for colon cancer? PMID- 11776486 TI - Surgery as adjuvant therapy? The treatment of peritoneal metastases from gastrointestinal malignancy. PMID- 11776487 TI - Evaluation of new diagnostic tests. PMID- 11776488 TI - Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. AB - BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5 flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT. PMID- 11776489 TI - Improved staging of node-negative patients with intermediate to thick melanomas (>1 mm) with the use of lymphatic mapping and sentinel lymph node biopsy. AB - BACKGROUND: Elective lymph node dissection (ELND) may contribute to a survival benefit in certain stratified subsets of melanoma patients. We hypothesized that lymphatic mapping and sentinel lymph node (SLN) biopsy (with complete node dissection if metastases are present) may improve both staging and survival of patients with clinically negative nodes, without subjecting all patients to the morbidity associated with complete ELND. METHODS: We reviewed the data for all 14,914 N0 patients of the AJCC Melanoma Staging Database to determine the effect of SLN biopsy and ELND on staging and survival. RESULTS: Retrospective analysis revealed that there was an apparent statistically significant survival advantage to SLN biopsy in patients with melanomas > 1 mm (n = 9024; 68.5% and 26.2% reduction in mortality compared with patients staged to be N0 by clinical exam and ELND, respectively; P < .0001). Five-year survivals were 90.5%, 77.7%, and 69.8%, respectfully, for patients staged by SLN biopsy (n = 2552), ELND (n = 2014), and clinical examination alone (n = 5192). The survival advantage of SLN biopsy was statistically significant for each T-stage category (T2, T3, and T4) and ulceration status. There was no advantage to SLN biopsy in patients with melanomas <1 mm (n = 5890). CONCLUSIONS: SLN biopsy provides more accurate staging and may contribute to a survival benefit in populations of patients with melanoma. PMID- 11776490 TI - Factors affecting survival after complete response to isolated limb perfusion in patients with in-transit melanoma. AB - BACKGROUND: Isolated limb perfusion (ILP) results in complete response (CR) rates of 60% to 90% in patients with regionally advanced melanoma. Survival after a CR may be influenced by various factors, particularly out-of-field disease in iliac lymph nodes (ILN) identified during lower-extremity ILP. We examined clinical and pathological parameters, including ILN status and outcome, for patients with in transit melanoma who had a CR to ILP. METHODS: From May 1992 to July 1997, 50 patients (16 men and 34 women; median age, 57 years) with stage IIIA or IIIAB melanoma had a CR to a 90-minute hyperthermic iliac ILP with melphalan (10 mg/L limb volume, n = 20) or melphalan and tumor necrosis factor (4-6 mg+/-200 microg interferon; n = 30). Clinical and pathological parameters were analyzed by univariate and Cox proportional hazards models to determine which were associated with survival or in-field recurrence. RESULTS: The median in-field recurrence free survival in the cohort of 50 patients after a CR to ILP was 1.4 years, and the actuarial 5-year in-field recurrence-free survival was 30%. By univariate analysis, there was a trend for improved outcome with female sex and stage IIIA (vs. IIIAB) at initial diagnosis was associated with improved survival after a CR to ILP (P = .056 and .012, respectively). Eleven (22%) of 50 patients had positive ILNs identified and resected at ILP. The probability of overall in-field recurrence was 70% after 4 years, and there was no difference between those with or without positive ILNs; median time to in-field recurrence was 13 and 19 months, respectively (P = .62). Similarly, overall survival was not influenced by positive ILN status (median [months]: +ILN, 69 vs. -ILN, 58; P = .68). Of note, Cox models identified that the risk of death was significantly greater in those with a history of prior systemic therapy (hazard ratio: 2.67 [95% confidence interval, 1.17-6.11]; P = .02) and those with an in-transit lesion size > or =1.4 cm2 (hazard ratio, 3.12 [95% confidence interval, 1.30-7.5]; P = .011). When these two variables were combined, there was a highly significant association with shortened survival (P = .002 by log-rank test). CONCLUSIONS: These data indicate that for patients undergoing ILP and in whom positive ILNs are found and resected, ILP is justified. In addition, patients who have a CR after ILP and have a history of prior treatment or larger lesions should be considered for adjuvant systemic therapy. PMID- 11776491 TI - A prospective study of 2-[18F] fluoro-2-deoxy-D-glucose/positron emission tomography scan, 99mTc-labeled arcitumomab (CEA-scan), and blind second-look laparotomy for detecting colon cancer recurrence in patients with increasing carcinoembryonic antigen levels. AB - BACKGROUND: An increasing carcinoembryonic antigen (CEA) level in the absence of disease on imaging studies can present a diagnostic challenge. We evaluated 2 [18F] fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) scan and CEA scan before second-look laparotomy as a means of localizing recurrent colorectal cancer. METHODS: Patients underwent computed tomography scan, bone scan, colonoscopy, and magnetic resonance imaging, and those without evidence of disease or resectable disease in the abdomen had FDG-PET and CEA scans. At second look laparotomy, a surgeon blinded to the results of the FDG-PET and CEA scans performed an exploration and mapped findings. A second surgeon, with knowledge of the FDG-PET and CEA scans, then explored the patient; all lesions were biopsied or resected for pathology. RESULTS: In 28 patients explored, disease was found at operation in 26 (94%). Ten had unresectable disease. FDG-PET scans predicted unresectable disease in 90% of patients. CEA scans failed to predict unresectable disease in any patient. In 16 patients found to have resectable disease or disease that could be treated with regional therapy, FDG-PET scan predicted this in 81% and CEA scan in 13%. CONCLUSIONS: FDG-PET scan can predict those patients who would likely benefit from a laparotomy. If the FDG-PET scan indicates resectable disease, laparotomy can be considered. However, if the findings predict unresectable disease or the absence of disease, the patient should pursue systemic therapy or continued observation. PMID- 11776492 TI - Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer. AB - BACKGROUND: Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome. METHODS: Patients having surgical debulking and IP 5-fluoro-2'-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively. RESULTS: There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m2 daily for 3 days) and IP leucovorin (240 mg/m2) with a median cycle number of 4 (range, 1-28). The median number of complications was 1 (range, 0-5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0-132 months). The median survival was 34 months (range, 2-132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection. CONCLUSIONS: Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator. PMID- 11776493 TI - Early postoperative oral feeding after colectomy: an analysis of factors that may predict failure. AB - BACKGROUND: Previous studies have shown that early postoperative oral feeding is feasible. Traditionally patients were fed when flatus or defecation documented the return of bowel function. This study was undertaken to determine factors that may preclude early feeding. METHODS: One hundred four successive patients underwent colorectal surgery from October 1999 to January 2001. Eighty-nine patients started an oral diet either on postoperative day 1 or 2. Their clinical outcomes were recorded prospectively. Fifteen of the 104 patients were excluded for small-bowel resection (5 patients), perioperative complications (5 patients), prior radiation (3 patients), and small-bowel obstruction (2 patients). A failure in postoperative feeding consisted of nausea, vomiting, or readmission. RESULTS: The mean age of our cohort was 65 years (range, 28-87 years). There were 45 male and 44 female patients. The mean postoperative hospital stay was 6 days (range, 3 13 days). The median American Society of Anesthesiology score was II (range, I IV). The types of resection performed were right colectomy (27 patients), low anterior resection (26 patients), sigmoid resection (11 patients), abdominoperineal resection (8 patients), formation or closure of colostomy (7 patients), posterior pelvic exenteration (4 patients), total colectomy (3 patients), left colectomy (2 patients), and transverse colectomy (1 patient). Sixty-five patients (73%) tolerated early oral feeding. Of the 24 patients that did not, 16 had nausea or emesis, and 8 required readmission for postoperative complications (small-bowel obstruction [4 patients], wound dehiscence [1 patient], abdominal pain [1 patient], and anastomotic leak [2 patients]). Univariate analysis revealed that the use of volume expanders contributed to intolerance of early feeding. On multivariate analysis, blood loss during the operation was the only factor contributing to failure of early postoperative oral feeding. CONCLUSIONS: Early oral feeding is safe and feasible for postcolectomy patients with a history of colorectal neoplasms. PMID- 11776494 TI - Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. AB - BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution. PMID- 11776495 TI - Expression and prognostic significance of O6-methylguanine-DNA methyltransferase in hepatocellular, gastric, and breast cancers. AB - BACKGROUND: O6-Methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs O6-methylguanine, a promutagenic DNA base damaged by endogenous and environmental alkylating agents. There are few reports that describe whether or not abnormal MGMT expression correlates with the prognosis in human solid cancers. METHODS: The expression of MGMT was immunohistochemically evaluated in 60, 62, 105, and 46 paraffin-embedded samples from patients with curatively resected hepatocellular, gastric, colorectal, and breast cancers, respectively. RESULTS: The expression of MGMT was a positive predictive factor for overall survival in hepatocellular (P = .005) and gastric cancers (P < .001) and for relapse-free survival in breast cancers (P < .001). MGMT-positive gastric tumors (n = 42) were correlated with the absence of serosal invasion (P = .045), lymph node metastasis (P = .006), intestinal type (P = .018), and low pathological tumor, node, metastasis stage (P < .001). All breast tumors that recurred locally after operation were MGMT negative (P = .004). The clinicopathologic characteristics of colorectal cancers with respect to MGMT expression did not significantly differ. CONCLUSIONS: The expression of MGMT is a predictive prognostic marker in patients with hepatocellular, gastric, and breast cancers. These findings may help to establish therapeutic strategies for patients with these types of solid cancer. PMID- 11776496 TI - The problem of the accuracy of intraoperative examination of axillary sentinel nodes in breast cancer. AB - BACKGROUND: Sentinel node (SN) biopsy has become accepted as a reliable method of predicting the state of the axilla in breast cancer. The key issue, however, is the accuracy of the pathological evaluation of the biopsied node, which should be done intraoperatively whenever possible. METHODS: In our initial experience on 192 patients using a conventional intraoperative frozen section method, the false negative rate was 6.3%, and the negative predictive value was 93.7%. We devised a new and exhaustive intraoperative method, requiring about 40 minutes, in which pairs of sections are taken every 50 microm for the first 15 sections and every 100 microm thereafter, sampling the entire node. Sentinel node metastases were found in 143 of the 376 T1N0 cases examined (38%). RESULTS: Metastases were always identified on hematoxylin and eosin sections, although in 4% of cases, cytokeratin immunostaining on adjacent sections was useful for confirming malignancy. In 233 patients the SNs were disease-free; of these patients, 222 had metastasis-free axillary nodes, and 11 (4.7%) had another metastatic node. CONCLUSION: Extensive intraoperative examination of frozen sentinel nodes correctly predicts an uninvolved axilla in 95.3% of cases (negative predictive value). This method is, therefore, suitable for identifying patients in whom axillary dissection can be avoided. PMID- 11776497 TI - Utility of breast sentinel lymph node biopsy using day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid. AB - BACKGROUND: In sentinel lymph node (SLN) biopsy for breast cancer, many centers use same-day preoperative injection of technetium 99mTc-labeled sulfur colloid and intraoperative injection of blue dye for localization of SLNs. Same-day sulfur colloid injections can be problematic because of the variability in sulfur colloid migration times, which can lead to ineffective use of operating room time, and low SLN-to-background radioactivity ratios. We examined the utility of day-before-surgery injections of high dose 99mTc-labeled sulfur colloid injections. METHODS: The day before surgery, high-dose 99mTc-labeled sulfur colloid was injected peritumorally, and a lymphoscintigram was obtained. Intraoperatively, after injection of blue dye, a gamma probe was used to localize SLNs. Nodes that were stained blue or were highly radioactive were considered SLNs and were removed. RESULTS: Lymphoscintigraphy demonstrated drainage in 107 patients (91%). Transcutaneous localization of the SLN was possible in 104 patients (89%). In three patients, all of whom had no drainage demonstrated on lymphoscintigraphy, no SLN was identified at surgery (97.5% success rate for SLN identification). A mean of 2.3 SLNs per patient were identified. Twenty-five patients (21%) had at least one histologically positive SLN. In 23 of these patients, the positive SLN was the SLN with the most radioactivity, and in the remaining two patients, the positive SLN was both blue-stained and hot. CONCLUSION: Day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid results in high rates of transcutaneous and intraoperative identification of SLNs. The delay between injection and surgery did not appear to promote significant passage of sulfur colloid to second-echelon nodes. PMID- 11776498 TI - Estrogen replacement therapy after breast cancer: a 12-year follow-up. AB - BACKGROUND: In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. METHODS: From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. RESULTS: Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. CONCLUSIONS: Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period. PMID- 11776499 TI - Utility of internal mammary lymph node removal when noted by intraoperative gamma probe detection. AB - BACKGROUND: Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection. METHODS: From April 1998 to July 2000, 1273 patients underwent LM for breast cancer. LM was performed using the combined dye and radiocolloid technique. Patients were scanned operatively with a gamma probe over the IMN area, and most underwent preoperative lymphoscintigraphy. Nodes were removed from patients in whom radioactivity was detected in the internal mammary area. RESULTS: Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Twenty-two of 30 (73.3%) had inner quadrant lesions. Five of 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had no metastatic spread to the axillary sentinel lymph node (SLN). One of thirty (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an SLN procedure. CONCLUSIONS: Radioguided SLN detection should be attempted in the IMN basin with all tumors. If an IMN is identified, it should be removed. IMN biopsy is a feasible, low-risk procedure when directed by radioguided LM and provides a guide for radiotherapy for patients with positive IMNs. PMID- 11776500 TI - Pathways of lymphatic drainage from the breast. AB - BACKGROUND: The current standard for obtaining accurate sentinel lymph node (SLN) mapping is intraparenchymal lymphophilic dye/radiocolloid injection close to the breast tumor. We hypothesized that common lymphatic trunks drain both a large volume of breast parenchyma and skin and that intradermal or intraparenchymal routes flow to the same axillary node. METHODS: 99mTc-labeled filtered sulfur colloid was injected intradermally directly over the breast tumor in 119 patients. Blue dye was injected intraparenchymally in the same quadrant as the primary tumor (concordant quadrant) in 66 and in a discordant quadrant in 53 patients. During axillary exploration, both blue and gamma-emitting (hot) nodes were found. End points were SLNs that were hot and blue, either the same node or different nodes. RESULTS: In 62 (93.9%) of 66 of concordant quadrant and in 49 (92.5%) of 53 of discordant quadrant patients, the same SLN was both hot and blue (P = .99; Fisher's exact test). In eight cases in which two distinct nodes were blue and not hot and hot but not blue, the lymph nodes were very close to each other. CONCLUSIONS: The dermal and parenchymal lymphatics of the breast seemed to drain to the same axillary lymph nodes. Lymph from the entire breast seemed to drain through a small number of lymphatic trunks to one or two lymph nodes. PMID- 11776501 TI - Geographical differences in primary therapy for early-stage breast cancer. AB - BACKGROUND: Breast-conserving surgery may not be uniformly available to all women. We evaluated geographical differences across Connecticut in the proportions of cases with early stage breast cancer treated by partial mastectomy (PM). We also looked at geographical variation in PM with axillary lymph node dissection (AND) and PM with adjuvant radiotherapy (RAD). METHODS: The Connecticut Tumor Registry identified 9106 cases of early disease for 1991 to 1995. Latitude-longitude coordinates for place of residence at diagnosis and initial form of therapy were available for 8795 records. A spatial scan statistic was used to detect geographical differences in treatment rates across the state. RESULTS: A total of 57.7% of early breast cancer cases were treated by PM. Women living around New Haven were less likely than others to be treated in that manner (relative risk [RR] = .86; P = .0001), whereas those living around Norwalk were more likely (RR = 1.26; P = .0001). PM with AND, relative to PM alone, was reported less often for cases from a large area of southwestern Connecticut (RR = .89; P = .0001), but more often for those in north central Connecticut (RR = 1.13; P = .0001). PM with RAD, relative to PM alone, was less common for cases around Danbury (RR = .40; P = .0001) but more common among cases around Hartford (RR = 1.14; P = .0001). CONCLUSIONS: Geographical analysis is a way for physicians and health officials to identify groups of women who may not yet benefit from preferred surgical procedures. PMID- 11776502 TI - Single intralesional tracer dose for radio-guided excision of clinically occult breast cancer and sentinel node. AB - BACKGROUND: The purpose of this study was to determine the feasibility of both lymphatic mapping and probe-guided primary tumor excision by use of intralesional tracer administration in clinically occult breast cancer. METHODS: Sixty patients with a clinically occult breast lesion were prospectively included. Lymphoscintigraphy was performed after intratumoral injection of 99mTc-labeled nanocolloid guided by ultrasound or stereotaxis. A catheter over a localization wire was inserted for intraoperative blue dye administration by using the same imaging techniques. After sentinel node identification, the gamma-ray detection probe was used for radio-guided wide local excision in patients who underwent breast-conserving therapy. RESULTS: A sentinel node was visualized on the scintigrams in 56 patients (93%) and could be identified intraoperatively in 58 patients (97%). A sentinel node contained tumor in 10 (17%) of these patients. Extra-axillary sentinel nodes were visualized in 43%, were collected in 38%, and contained metastasis in 7% of the patients. Complete excision of the primary tumor could be accomplished in 39 (87%) of 45 patients. CONCLUSIONS: Both sentinel node biopsy and probe-guided excision of a nonpalpable breast cancer is feasible with the aid of intralesional tracer administration. Sentinel node metastasis was found in 17% of the patients. A remarkably high percentage of extra-axillary drainage (43%) was observed. PMID- 11776503 TI - Minimally invasive, radioguided surgery for primary hyperparathyroidism. AB - BACKGROUND: Primary hyperparathyroidism affects 1 in 700 individuals in the United States. A single adenoma is responsible in over 85% of cases. Surgery remains the most effective treatment. This study was designed to assess the feasibility of minimally invasive radioguided parathyroidectomy (MIRP) with confirmation of excision by ex vivo radioactivity alone. METHODS: Seventy-five consecutive patients with primary hyperparathyroidism were prospectively studied. Following sestamibi scan, patients underwent unilateral neck exploration guided by a handheld gamma probe, which was also used to measure ex vivo radioactivity of excised tissue. RESULTS: The sestamibi scan was positive in 88% of the patients. A small incision (mean, 3.2+/-0.3 cm) was sufficient. Ectopic gland sites were localized in five patients with positive scans and single adenomas. Mean operative time was 48 minutes (range, 15-125 minutes), with shorter procedures after the initial 20 cases (mean, 24 vs. 72 minutes; P < .01). Radioguided parathyroidectomy was successful in 97%, with a mean follow-up of 11 months (range, 1-26 months). As noted previously, adenomatous parathyroid glands contained more than 20% of the background radioactivity. CONCLUSIONS: MIRP is a feasible alternative to bilateral dissection with the advantages of guided dissection and rapid confirmation, and may become the procedure of choice for primary hyperparathyroidism. PMID- 11776504 TI - Prenatal diagnosis of isolated anorectal atresia with colonic perforation. AB - We report here a case of prenatal diagnosis of isolated anorectal atresia with intrauterine colonic perforation at 34 weeks of gestation, characterized by the presence of a bilobed cystic pelvic mass with a V-shape appearance separated from the bladder with changing features during observation. Mild ascites was also visualized. Other structures were normal on detailed ultrasound. The patient had spontaneously delivered a male infant weighing 2,100 g at 34 weeks of gestation. The infant died one day after birth, before surgical correction secondary to respiratory distress syndrome. Autopsy revealed isolated anorectal atresia, and high (supraelevator) lesions. In conclusion, the findings of bilobed cystic pelvic mass with a V-shape were useful to diagnose anorectal atresia in this case. Prenatal ultrasound can facilitate early diagnosis and treatment. PMID- 11776505 TI - Indomethacin therapy in the treatment of polyhydramnios due to placental chorioangioma. AB - A 26-year-old primigravida presented with acute polyhydramnios at 30 weeks gestation. Ultrasonography revealed a large placental chorioangioma with severe hydramnios. No anomalies were detected in the fetus. Preterm labor started with respiratory distress and indomethacin, 25 mg was given every 6 hours. The patient showed a good response with improvement of the hydramnios and respiratory symptoms. A normal infant with no neonatal complications was delivered 3 weeks later. PMID- 11776506 TI - Umbilical artery blood acid-base analysis and fetal heart rate baseline in the second stage of labor. AB - OBJECTIVE: To evaluate the correlation between umbilical arterial acidemia and second-stage baseline fetal heart rate (FHR) abnormalities in Japanese newborn infants. METHODS: Subjects were 365 newborns, born at term. Specimens were obtained from the umbilical artery as soon as possible after delivery and blood gas determinations were performed within 5 minutes of delivery. FHR monitoring was performed in the second stage. RESULTS: Umbilical arterial acidemia occurred in 54.1% of the newborns with moderate to severe bradycardia, in 27.3% with mild bradycardia, and in 19.3% with tachycardia, compared with only 1.3% of those with a normal FHR (p < 0.001). The mean umbilical arterial base excess was significantly greater in newborns with metabolic acidemia (-13.9+/-2.9 mmol/l) than in those with either mixed (-11.5+/-2.8 mmol/l) (p < 0.02) or respiratory ( 9.1+/-3.2 mmol/l) (p < 0.01) acidemia. CONCLUSION: The second-stage baseline FHR abnormalities were highly correlated with an increased risk of umbilical arterial acidemia at delivery. PMID- 11776507 TI - The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. AB - OBJECTIVES: To compare the effects of estradiol vaginal tablet with conjugated estrogen cream on urogenital symptoms, vaginal health index, vaginal cytology, endometrial thickness, and plasma estradiol level in postmenopausal women. METHODS: Fifty-three women with urogenital symptoms were randomized to local vaginal treatment of 25 microg estradiol tablet or 1 g of conjugated estrogen cream for 12 weeks. They were assessed for urogenital symptoms, vaginal health index, vaginal cytology, endometrial thickness and estradiol level. RESULTS: Forty-eight women completed the treatment. Both groups showed improvement of urogenital symptoms, vaginal health index, and vaginal cytology after the first 4 weeks of treatment. Conjugated estrogen cream showed superior efficacy in alleviating vaginal dryness and dyspareunia. Two cases of endometrial proliferation were noted. CONCLUSIONS: Estradiol vaginal tablet and conjugated estrogen cream were effective in treating urogenital symptoms, the restoration of normal vaginal epithelium and reduction of vaginal pH in postmenopausal women. However, 2 cases of endometrial proliferation were noted. PMID- 11776508 TI - Use of gonadotrophin releasing hormone (GnRH) antagonist (cetrotide) during ovarian stimulation for in-vitro fertilization treatment: multiple doses and single dose. AB - OBJECTIVES: To report preliminary experience in using the GnRH antagonist (Cetrotide) and to compare the multiple dose and single dose protocols. METHODS: Fifteen patients received multiple doses and another 10 patients received the single dose protocol of GnRH antagonist during ovarian stimulation for IVF treatment. Outcome measures included the duration/dosage of gonadotrophin and number of oocytes aspirated. RESULTS: All patients had successful oocyte retrieval after the hCG injection. The single dose group had a significantly shorter duration of gonadotrophin but fewer frozen embryos than the multiple dose group. CONCLUSIONS: Both protocols were effective in preventing premature LH surges. The stimulation regimen was simplified by reducing the total treatment period, the dosage and duration of gonadotrophin. There may be differences in ovarian responses between the two protocols. PMID- 11776509 TI - Pregnancy complicated with Bartter's syndrome: a case report. AB - Bartter's syndrome is a rare renal disorder, and since there are few case reports of Bartter's syndrome complicating pregnancy are few, the changes of electrolytes and hormonal metabolism during pregnancy are unknown. We describe and discuss the course of pregnancy complicated with Bartter's syndrome. PMID- 11776510 TI - Sonographic fetal weight estimation in a south-east Asian population. AB - OBJECTIVES: To determine the optimal sonographic fetal weight estimation formula for a mixed south-east Asian population near term. METHODS: Seventy-eight uncomplicated pregnancies were monitored between January 1996 and January 1997. Biparietal diameter, head circumference, abdominal circumference and femur length were measured and the following formulae were tested: Campbell, Shepherds and Hadlock. The estimated fetal weight was calculated by 12 different methods. The weight estimate was then projected forward to the time of delivery using the gestation-adjusted forward projection method. The weight estimation error was derived from the difference between the projected fetal weight and birth weight, and expressed as a percentage of birth weight. RESULTS: The mean time interval from the time of ultrasound fetal weight estimation to delivery was 4.4 days. The birth weight ranged between 2,330 to 4,215 g. The best performing formula was Hadlock's formula using the head circumference, abdominal circumference and femur, with the perimeters calculated using the ellipse function. The standard deviation of error for this formula was 8.66%. CONCLUSION: Even though the Hadlock formula was originally derived from an American population, it was equally useful in south-east Asian population. PMID- 11776511 TI - A new hysteroscopic tubal embryo transfer catheter: development and clinical application. AB - OBJECTIVE: Development and clinical application of a new hysteroscopic tubal embryo transfer catheter. METHOD: Catheterization was performed in 60 patients at hysteroscopic insemination into tube, using 3 French catheters, in which the distal 3, 4, and 5 cm tapered to 2 French. Hysteroscopic tubal embryo transfer and conventional IVE-ET were performed in 30 patients with normal tubes, who failed to achieve pregnancy after 2 IVF-ET trials. RESULT: The success rate of complete insertion with the catheter tapering at the distal 3 cm was significantly higher than that at the distal 5 cm. Since we obtained the highest success rate of insertion with the catheter tapering at the distal 3 cm, we selected this catheter for the h-TEST. The rate of pregnancy in h-TEST was significantly higher than that in conventional ET. CONCLUSION: The h-TEST using our catheter was useful for establishing pregnancy in assisted reproduction. PMID- 11776512 TI - Lymphatic filariasis of the ovary and mesosalpinx. AB - We report 2 cases of filariasis, one in the ovary and the other in the mesosalpinx. In the first case, the patient underwent panhystrectomy and in the second case, right ovarian cystectomy with right salpingectomy were performed under general anaesthesia. Histopathology showed adult filarial worms in the dilated lymphatics of the right ovary, in the first case and in the mesosalpinx, in the second case. Both patients presented with complaints related to gynecological problems and not filariasis. Reports of filariasis in the literature and possible treatments and prevention strategies are also discussed. PMID- 11776513 TI - Lymphangioma circumscriptum of the vulva mimicking genital wart: a case report and review of literature. AB - Lymphangioma circumscriptum (LC) is an uncommon dermatologic problem that rarely affects the vulva and it is considered to be a localised developmental defect of lymphatic tissue in the dermis. We report a case of vulval LC, clinically diagnosed as genital wart, in a 48-year-old woman without evidence of secondary lymphatic damage. The patient required extensive vulval surgery and there was no recurrence after 16 months. PMID- 11776514 TI - A comparative study of intraplacental villous arteries by latex cast model in vitro and color Doppler flow imaging in vivo. AB - OBJECTIVE: The purpose of this study was to determine whether color Doppler sonogram can accurately depict the placental vascular structures using a latex cast model of the placental vessels, and to make a nomogram of several blood flow parameters according to the vascular structures. METHODS: First, we made 9 latex cast models of placental arteries and performed morphologic observation and measurement. Second, the comparative anatomical observation of placental vessels by color flow mapping was performed for all 9 patients from whom the latex models were made. Third, a total of 102 uncomplicated pregnant women between 18 and 40 weeks gestation were examined by color Doppler imaging. The resistance indices (RI) and peak systolic velocity (PSV) were measured. RESULTS: In the latex cast model of placentas, cotyledons could be differentiated by the presence of independent vascular structure units. First, second, third and fourth branches were noted in one cotyledon. Cotyledons were easily identified and counted by color Doppler imaging. Each cotyledon contained only one first branch of the intraplacental villous artery (IPVA). The number of IPVA-1 on color Doppler imaging was equal to the number of the cotyledon calculated from the latex model. RI exhibited a negative, and PSV a positive correlation with gestational age (p < 0.05 in both cases). At any given gestational age, both RI and PSV in the peripheral arteries were significantly lower (p < 0.01) than those in the upstream arteries. CONCLUSIONS: Color Doppler flow sonography is a valuable tool for detecting the blood flow of intraplacental villous arteries in vivo and the images agree with the vascular anatomy of placenta in vitro. These results may also provide the basic parameters for future studies of some complicated pregnancies. PMID- 11776515 TI - [High-level expression of Mycobacterium tuberculosis 16,000 antigen in E. coli]. AB - OBJECTIVE: To gain the recombinant protein antigen 16,000 of Mycobacterium tuberculosis highly expressed in E. coli and study its immunological characteristics. METHODS: DNA fragments code for the protein were obtained by PCR, then cloned into the pET plasmid vector to gain recombinant E. coli. Cells were cultured and induced to produce recombinant protein, whose molecular size and present form were analyzed by SDS-PAGE, and its immunological characteristics were analyzed by Western-blotting and ELISA technology. RESULTS: The clone was analyzed at the nucleotide lever and shown the same DNA sequence coding for natural 16,000 protein. Analyzed by SDS-PAGE and Western-blotting, it was found to produce immunoreactive proteins with mobilities very similar to those of the 16,000 protein antigen, and the recombinant protein amounted to 40% of total cell proteins. ELISA results indicated that the purified recombinant protein could distinguish sera from tuberculosis patients with anti-PPD antibody and those from tuberculin positive contacts. CONCLUSIONS: Recombinant 16,000 protein antigen highly expressed in the form of solution in E. coli was gained and this antigen was located in cell plasma. This recombinant protein showed specific immunogenicity. PMID- 11776516 TI - [Identification of postoperative M. chelonae infection outbreak by polymerase chain reaction of 16s-23s ribosomal DNA spacer sequence]. AB - OBJECTIVE: To determine the pathogen of the infection outbreak in a hospital in Shenzhen at gene level with molecular biological technique, and to establish a rapid identification method of M. chelonae subsp. abscessus by polymerase chain reaction technique. METHODS: A single pair of primers and oligonucleotides probe of M. chelonae subsp. abscessus were designed, according to the sequence of mycobacterium of 16s-23s ribosomal DNA spacer sequences. 53 clinical strains were amplified by polymerase chain reaction, then dot-blot hybridization of PCR product was made. On the basis of this study, 259 lesion, tissue and normal tissue were amplified by 16s-23s rDNA PCR. RESULTS: 380 bp PCR product for 53 clinical strains was yielded by 16s-23s rDNA PCR, in the meantime, the specific hybridization dot appeared. The PCR positive rate of 259 specimens was 60.6%. CONCLUSIONS: The PCR products and dot-blot hybridization showed that the pathogen of the infection outbreak was M. chelonae subsp. abscessus at gene level. The 16s 23s rDNA PCR investigative system is sensitive and specific, which can identify M. chelonae subsp. abscessus. PMID- 11776517 TI - [Study on expression of apoptosis related genes in non-small cell carcinoma]. AB - OBJECTIVE: To study the relationship between the expression of apoptosis related genes in the tissue of non-small cell lung carcinoma (NSCLC) and clinicopathology in the tumor. METHODS: The expression of bcl-2, bax, Fas and FasL were detected with immunohistochemistry method in 45 cases of NSCLC. RESULTS: 23 (51%) cases of NSCLC were bcl-2 positive, 38 (84%) were bax positive (P < 0.01), and there was no significant correlation between the expression of bcl-2 and bax protein, but a positive relationship was found between the expression of Fas and FasL (P < 0.01). The positive rate of bcl-2 expression decreased in advanced stages of NSCLC(P < 0.05), the bax expression was lower in cases with poor cell differentiation (P < 0.05), and the FasL expression was higher in adenocarcinoma (P < 0.01). The simultaneous expression of bcl-2 and bax protein was closely correlated with TNM stages (P < 0.05), the differences of bcl-2 protein expression alone in NSCLC with cell differentiation were statistically significant (P = 0.033). CONCLUSIONS: Both bcl-2, bax, Fas and FasL may involve in the regulation of apoptosis and may play an important role in the occurrence and progression of NSCLC. PMID- 11776518 TI - [Expression of multidrug resistance-associated protein in human non-small cell lung cancer]. AB - OBJECTIVE: To investigate the expression of the multidrug resistance-associated protein(MRP) gene and MRP in human non-small-cell lung cancer tissues and to determine whether such expression was related to cell type, differentiation, tumour size, lymph node metastasis and prognosis. METHODS: 92 paraffin-embeded lung tumor samples (43 squamous cell carcinoma, 49 adenocarcinoma) and 16 fresh non-small-cell lung cancer samples were examined by using immunohistochemistry method and the reverse transcription-polymerase chain reaction (RT-PCR) technology respectively. RESULTS: The expression of MRP mRNA and MRP were detectable in 31% (5-16) and 54% (50/92) of non-small-cell lung cancer specimens respectively. Eighteen(42%) squamous cell carcinoma specimens and thirty-two(65%) adenocarcinoma specimens showed positive immunostaining for MRP(P < 0.05). The expression of MRP was not related to tumour size, lymph node metastasis and cell differentiation significantly(P > 0.05). The five-year survival rate after operation of patients with MRP-positive tumours and MRP-negative tumours were 16% (8/50), 52% (22/42) respectively. Patients with MRP-positive tumours had shorter survival time than the MRP-negative patients significantly(P < 0.01). CONCLUSIONS: Adenocarcinoma had higher MRP expression than squamous carcinoma significantly, positive MRP immunostaining appears to be an independent indicator of poor prognosis in NSCLC. PMID- 11776519 TI - [Clinical study of metastasis of thoracic lymph node in resectable lung cancer]. AB - OBJECTIVE: To study the metastatic pattern of thoracic lymph node in resectable lung cancer. METHODS: From January 1992 to July 1998, the lymph nodes in hilar(N1) and mediastinal(N2) were resected based on their distribution in 160 patiens with resectable lung cancer and were examined by pathology. Number, size and colour of lymph nodes in each regions were recorded. Each lymph node was examined by routine pathology and immunohistochemistry. Quantity of metastatic lymph node was reported according to their regions. RESULTS: 99 cases(61.9%) had thoracic lymph nodes metastasis and 73 cases (45.6%) had mediastinal lymph nodes metastasis. Of those, only N1 metastasis was 16.3%, from N1 to N2 metastasis was 32.5%, only N2 metastasis was 13.1%. The metastatic frequencies in 11, 10, 7, 5 and 4 regions around the hilar or root of lung were 30.0%, 27.5%, 16.9%, 28.8% and 20.0%, respectively. Those were higher than 9, 6, 3, 2 and 1 regions far from the root of lung. The metastatic rate of lymph node in 2.0 cm or greater, 1.0 cm or greater and less than 1.0 cm was 60.7%, 15.5% and 4.3%, respectively (P < 0.001). The smallest metastatic lymph node was only 0.2 cm x 0.2 cm. Statistical analysis revealed that metastatic rate of thoracic lymph nodes was not relevant to different area, size and course of tumors. CONCLUSIONS: The lymph nodes metastases of most cases were spreading from the near to the distant, from lower to upper, through the hilar to the mediastinal. Lymph nodes metastases occurred easier in SCLC than in NSCLC (P < 0.05). It must be depended on pathologic examination to confirm whether or not the tumor has metastasis to lymph node. PMID- 11776520 TI - [Clinical study of fibrinolysis indicators in patients with chronic pulmonary heart disease]. AB - OBJECTIVE: To investigate the change of D-dimer and other fibrinolysis indicators in patients with chronic pulmonary heart disease. METHODS: The fibrinolytic activity of plasma was measured in 42 patients with chronic pulmonary heart disease and in 20 controls (matched with sex and age). RESULTS: The D-dimer level was significantly higher in exacerbated patients than in controls (P < 0.001). The fibrinolytic activity in patients was lower than in controls. The plasma fibrinolytic activity was positively correlated with PaO2 and negativly correlated with PaCO2. CONCLUSIONS: The depressed fibrinolysis may be associated with hypercoagulability state of chronic pulmonary heart disease and contributes to thrombi in small pulmonary arteries and arterioles. D-dimer can be used in diagnosis of thrombi formation in small pulmonary arteries and arterioles. Patients with chronic pulmonary heart disease can be treated with fibrinolysis drugs. PMID- 11776521 TI - [The clinical study of pulmonary emphysema with pulmonary fibrosis]. AB - OBJECTIVE: Emphysema and interstitial pulmonary fibrosis are two different diseases in clinical manifestation and pathology, but it was noticed that there were cases diagnosed as pulmonary emphysema and pulmonary fibrosis. It is necessary to study the relationship between the clinical aspects of these cases. METHODS: 11 patients with emphysema and pulmonary fibrosis were found in the past five years. Clinical symptoms, radiographic features, arterial blood-gas, lung function testing and computed tomography of the chest were analyzed. RESULTS: These patients had a long history of cigarette-smoking. Their clinical features are those of both emphysema and pulmonary fibrosis. CONCLUSIONS: Although emphysema and interstitial pulmonary fibrosis are two different diseases, they could coexist in some patients. Their clinical features do not like either of the two diseases. HRCT is an important method for discovering the coexistance of pulmonary emphysema and interstitial fibrosis. PMID- 11776522 TI - [Polymorphism of angiotensin-converting enzyme gene and susceptibility to asthma with familial aggregation]. AB - OBJECTIVE: Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin II (AT II) and inactivation of bradykinins and tachykinins, which are potent bronchial constrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. Whether or not the polymorphism of ACE gene is associated with asthma and bronchial responsiveness was investigated. METHODS: A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine broncho(Mch)-provocation and pulmonary function tests were performed in all asthmatics. RESULTS: There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46% vs 16%, P < 0.05; Odd ratio 4.98). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (74% vs 57%, P < 0.05; 79% vs 69%, P < 0.05, respectively). CONCLUSIONS: The results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction. PMID- 11776523 TI - [Effects of ventilation and surfactant perturbation on alveolocapillary permeability]. AB - OBJECTIVE: To investigate the effects of large tidal volume ventilation (LTVV) and surfactant dysfunction induced with dioctyl sodium sulphoccinate (DOSS) on alveolocapillary permeability, and on the surface tension of lung tissue extract (LTE). METHODS: The permeability index of tecthnetium-99m labelled human serum albumin (99mTc-HSA) was used to characterize the alveolocapillary permeability after LTVV and surfactant dysfunction permeability index, dynamic respiratory compliance (Cdyn), arterial blood gas (ABG), wet lung weight and surface tension of LTE were measured in four groups of rabbits: (1) controls; (2) LTVV; (3) DOSS; and (4) DOSS + LTVV. RESULTS: Cdyn and ABG were stable throughout the experiment in all groups. The wet lung weight was (1.85 +/- 0.16) g/kg, (2.50 +/- 0.27) g/kg, (1.88 +/- 0.12) g/kg and (2.65 +/- 0.13) g/kg in four groups respectively. It was significantly increased in LTVV and DOSS + LTVV groups compared with controls and DOSS (P < 0.01). The permeability index was 0.10 +/- 0.04, 0.72 +/- 0.14, 0.13 +/- 0.03 and 0.79 +/- 0.17 in four groups respectively. There was a significantly increased permeability index in LTVV and DOSS + LTVV groups compared with controls and DOSS (P < 0.01). There was no difference of surface tension of LTE among all groups. CONCLUSIONS: The results of this study suggest that the increased alveolocapillary permeability, pulmonary edema and lung injury are induced by LTVV rather than DOSS. The mechanisms of HSA transferring alveolocapillary membrane from different directions are different. PMID- 11776524 TI - [Follow-up study of lung function changes for 10 years in healthy elder of ex smokers]. AB - OBJECTIVE: To observe changes of lung function for 10 years in healthy elderly ex smokers who have quitted smoking for more than 10 years. METHODS: 51 healthy elderly ex-smokers were selected and routine lung function tests were performed, 12 subjects, who have never smoked and all other criteria were similar, were chosen as controls. Their routine lung function tests have also been followed up for 10 years. RESULTS: The decrease of VC, FVC, FEV1 and PEF of ex-smokers were significantly lower than non-smokers, the increase of RV and RV/TLC were significantly higher than non-smokers. FEV1/FVC, MVV, MMEF, FRC and TLC were also different, however, the difference has not reached statistically significant. CONCLUSIONS: The influence of smoking could be prolonged, even the subject has stopped smoking for years, so we suggested to stop smoking the early the better. PMID- 11776525 TI - [Carcinoma of the lips developing in discoid lupus erythematosus]. AB - OBJECTIVE: This clinical study was designed to learn the diagnosis and treatment of lip carcinoma developing in discoid lupus erythematosus. METHODS: One hundred and eighty-one of squamous cell carcinoma of the lips treated in our department from 1980 to 1995 were retrospectively studied. RESULTS: Ten cases of the 181 lip carcinoma (5.5%) had concomitant discoid lupus erythematosus (DLE) of the vermilion border of the lower lip. CONCLUSION: Bleomycin or radiotherapy is the best treatment for the disease. PMID- 11776526 TI - [Analysis on curative effects of teeth with chronic apical periodontitis in elderly people]. AB - OBJECTIVE: To study of the curative effect of teeth with chronic apical periodontitis in elderly people and the usage of assessment index. METHODS: Fifty eight teeth from 49 elderly and 50 teeth from 40 young patients were reexamined, which had received root canal therapy or resinifying therapy 2 to 9 years ago. The curative effects were evaluated based on clinical examination and radiographic assessment using periapical index (PAI). RESULTS: Statistically no significant difference for the overall healing rates between the two groups. But when the reexamination period was longer than 4 years, the healing rates in elderly people (58.0%) were significantly lower than those of the young people (87.1%). The treatment method and the size of the periapical lesion had significant influence on the results of the elderly people, whereas no influence on the young patients. According to our data, deep periodontal pocket and occlusal trauma were the main reasons of failure. CONCLUSION: The long-term curative effects of teeth with chronic apical periodotitis in elderly is lower than that of the young people. The PAI system is worth of utilizing popularly in the clinical dentistry. PMID- 11776527 TI - [A study on the conjugation of Streptococcus mutans adhesins and its salivary receptors]. AB - OBJECTIVE: To investigate the conjugation specificity of Streptococcus mutans' adhesins and their salivary receptors. METHODS: Include purified salivary receptor or adhesin competitive bacteria adhesion inhibition test and enzyme linked immuno-receptor assay (ELIRA) on S. mutans WD9463A. RESULTS: Salivary amylases can both enhance and competitively inhibit the adhesion of the strain to HA, while IgA degraded fragments and MW = 13,000 protein only promote its adhesion. P1 and a 117,000 surface protein of WD9463A both inhibit adhesion of the strain to IgA degraded fragments and salivary amylases. An 127,000 protein of WD9463A and a kind of GTFase inhibit its adhesion to IgA degraded fragments and salivary amylases respectively. No conjugation was found between IgA degraded fragments and the adhesins, while reaction between amylases and the adhesins had basically accordance with adhesion inhibition test. CONCLUSION: The adhesion of S. mutans is a result of reaction between multireceptors and multiadhesins. PMID- 11776528 TI - [A study of load stress on an implant and a tooth supported fixed bridge for the first mandibular molar]. AB - OBJECTIVE AND METHODS: A study of load stress on an implant and a tooth supported fixed bridge for the first mandibular molar was performed by means of 3-D FEA in order to reveal the displacement and stress distribution. RESULTS: The results show that the maximum displacement of the second premolar is greater than that of the terminal implant, but there is no difference between the mean (mean) under dispersed load statistically, due to the framework function of the bridge. The stress concentration appears around the neck of the abutments, on the contrary, a little stress is found around the apical portion of the second premolar. When the load concentrates on-to the abutments, the displacement and stress value increase obviously. CONCLUSION: The attention should be paid to the load and occlusion of the terminal implant. This kind of bridge design may be used in clinical practice. PMID- 11776529 TI - [Effects of laminin on the invasive and metastatic behaviors of human salivary adenoid cystic carcinoma cell lines]. AB - OBJECTIVE: To study the effect of laminin (LN) on invasive and metastastic behaviors of salivary adenoid cystic carcinoma (Acc) cell lines. METHODS: Immunohistochemistry, Boyden chamber in vitro motility, and adhesion test were used. LN and LNR (LN receptor) distributions in Acc-2 and Acc-M cells were studied with immunohistochemical staining. RESULTS: There were less LN and LNR found in Acc-2, but much more LN and LNR were present in the highly metastatic clone Acc-M. With the presence of exgenous LN, Acc-2 became activated showing a higher migration rate. The cell adhesion test showed that Acc-2 had stronger ability of adhesion than Acc-M with the presence of LN. CONCLUSION: The result suggests LN and LNR may play a vitral role in the invasion and metastasis of Acc. PMID- 11776530 TI - [Correction of the secondary nasal deformities of the unilateral cleft lip and palate]. AB - OBJECTIVE: To develop a new method to correct secondary nasanl deformities of cleft lip and palate. METHODS: Establishing the balance of maxilla on both sides, followed by varied procedures to correct anormaly of osseous-cartilagious framework of nose, and taking some of nasal-labial muscle to restore the continuity and balance of anterior facial expressive muscles. RESULTS: 78 cases were treated by this way and the result was satisfying. CONCLUSIONS: Imbalance of maxilla and anterior facial expressive muscle and anormaly of nasal framework should be repaired for correcting the nasal deformity of cleft lip and palate effectively. PMID- 11776531 TI - [Growth behavior of cells of ameloblastoma and odontogenic keratocyst]. AB - OBJECTIVE: To compare the growth behavior of epithelium and fibroblast from ameloblastoma and keratocyst and to discuss the recurrence reason for the keratocyst. METHODS: Epithelial cells and fibroblast from ameloblastoma, keratocyst, dentigerous cyst, radicular cyst and oral mucosa were cultured and observed by phase-contrast microscope. RESULTS: The epithelial cells of ameloblastoma grew faster, with an irregular area around the cell mass and some small satellite-shaped cell mass. The epithelial cells of all the cysts and mucosa grew slower with the cell masses surrounded by fibroblasts which grew in whirl manner with a round and smooth periphery. CONCLUSION: The cells from the ameloblastoma grow faster and more active, and those from the keratocysts grow like the other cysts and the normal mucosa. It is speculated that the ameloblastoma grows in an aggressive manner and it is possible that the recurrence of the keratocyst isn't primarily resulted from its growth behavior as a tumor. PMID- 11776532 TI - [Analysis of mandibular movement and functional classification for malocclusion patients]. AB - OBJECTIVE: To classify the paths of mandibular movements of patients with malocclusion. METHODS: 223 patients were examined clinically and mandibular Kinesiograph(MKG) was applied. RESULTS: Each kind of malocclusion has its corresponding characteristic paths of mandibular movement. The paths of mandibular movements of patients with the same class of malocclusion are similar. It was also found that the mandibular movement was related not only with occlusion but also with jaws, muscles, and joints. Meanwhile, they affect each other. CONCLUSION: Functional malocclusion classification includes functional class I, II, III and IV malocclusion. PMID- 11776533 TI - [A study on the cariogenic bacteria of plaque on abutment teeth of casting and wrought wire clasp removable partial dentures]. AB - OBJECTIVE: The effect of clasp on the health of abutment teeth. METHODS: To analyse and compare the cariogenic bacteria plaque getting from the buccal cervical third of casting and wrought wire clasp teeth before and one week after wearing removable partial dentures. RESULTS: The average percentages of Streptococcus Mutans and Actinomyces Viscosus in total culturable bacteria rised significently in statistical analysis, but there was no significent difference of Lactobacilli. The average percentage of Actinomyces Viscosus increased less after wearing casting clasp RPD than that of wrought wire clasp. CONCLUSION: Clasps of RPD increased the risk of root caries of abutment teeth. However the influence of casting clasps was smaller than that of wrought wire clasps. PMID- 11776534 TI - [Relationships between mandibular canine calcification stages and skeletal maturity]. AB - OBJECTIVE: To study the relationship between mandibular canine calcification and skeletal maturity. METHODS: Hand wrist and mandibular canine radiographs of 106 boys and 152 girls in Beijing area were assessed. RESULTS: Mandibular canine calcification coincides with the initiation of puberty in male (93.8%) and with the deceleration of puberty in female(89.7%). However the coincidence with the indicators of other pubertal stages was less than 50%. CONCLUSION: Mandibular canine calcification just can give an initial assessment for estimating the timing of puberty. PMID- 11776535 TI - [A preliminary study on dental-manpower forecasting model of Miyun County in Beijing]. AB - OBJECTIVE: To explore the dental-manpower forecasting model of Chinese rural region and provide references for Chinese dental-manpower researches. METHODS: Chose rural Miyun County in Beijing as a sample, according to the need-based and demand-weighted forecasting method, a protocol WHO-CH model and corresponding JWG 6-M package developed by authors were used to calculate the present and future need and demand of dental-manpower in Miyun County. Further predications were also calculated on the effects of four modeling parameters to the demand of dental manpower. RESULTS: The present need and demand of oral care personnel for Miyun were 114.5 and 29.1 respectively. At present, Miyun has 43 oral care providers who can satisfy the demand but not the need. The change of oral health demand had a major effect on the forecast of the manpower. CONCLUSION: Dental manpower planning should consider the need as a prime factor but must be modified by the demand. It was suggested that corresponding factors of oral care personnel need to be discussed further. PMID- 11776536 TI - [The elastase activity in gingival crevicular fluid from rapidly progressive periodontitis]. AB - OBJECTIVE: It is now generally accepted that polymorphonuclear neutrophil (PMN) chemotactic defect increases the patient's susceptibility to early-onset periodontitis. However, some reports including ours have failed to show defective PMN chemotaxis in rapidly progressive periodontitis(RPP) patients. The purpose of the study was to survey the role of PMN in the progression of RPP. METHODS: The elastase activity in gingival crevicular fluid from 22 RPP patients and 11 healthy controls were studied. For the control group and 12 RPP patients, 30 s GCF and clinical data were obtained at the first visit. For other 10 RPP patients, 30 s GCF and clinical data were collected prior to treatment and 4 weeks after scaling and root-planing. The elastase activity was measured with a low molecular weight substrate (L-Pyroglutamyl-L-prolyl-L-valine-p-nitroaniline, S2484) specific for granulocyte elastase. RESULTS: The pre-treatment elastase activity was much higher (0.63 +/- 0.38, Abs/site) in RPP patients than that in control subjects (0.07 +/- 0.05, Abs/site). The elastase activity was positively correlated with GCF volume, probing depth, attachment loss and gingival bleeding. Scaling and root-planing resulted in decrease of both clinical data and elastase activity. CONCLUSION: These results suggested that PMN with the increased accumulation or the increased release of lysosomal enzymes may play a role in the pathogenesis of RPP. PMID- 11776537 TI - [Helicobacter pylori in dental plaque of periodontitis and gastric disease patients]. AB - OBJECTIVE: To investigate whether Helicobacter pylori(Hp) is a habitant in the oral cavity. METHODS: A polymerase chain reaction (PCR) assay with oligonucleotide primers homologous to a portion of the urease C and cytotoxin associated gene A (cag A) of Hp was used to test for the presence of Hp in dental plaque. This assay was able to detect the expected 294 bp and 400 bp DNA fragments from as few as 100 Hp cells per reaction. Thirteen gastric disease patients (Group G) and 10 periodontitis patients (Group P) were recruited. A total of 276 supra- and subgingival plaque samples were collected, from 6 teeth in each subject for PCR assay. Clinical periodontal parameters including probing depth (PD), bleeding index (BI) and plaque index (PLI) of the sampled sites were recorded. RESULTS: In Group G, 11 of 13 patients had at least one Hp-positive plaque sample. 28.8% of the tested samples were urease C gene positive and 3.2% were positive for both urease C and cag A genes. All the 10 patients in Group P had at least one Hp-positive plaque sample. 49.2% of the tested samples were urease C gene positive and 3.3% were positive for both of the Hp genes. The prevalence of Hp was positively correlated with probing depth and bleeding index at the sampled sites. CONCLUSION: These results suggest that oral cavity is an ecological niche of Hp. PMID- 11776538 TI - [Absorbed doses to critical organs from full mouth dental radiography]. AB - OBJECTIVE: A few studies were reported in China on radiological risk of dental radiography. The aim of this study is to evaluate the absorbed doses of patients from the full mouth radiographs, and to find out the contribution from each projection to the total absorbed dose of the organs. METHODS: Absorbed doses to critical organs were measured from 14-film complete dental radiography. The organs included pituitary, optical lens, parotid glands, submandibular glands, sublingual glands, thyroid, breasts, ovary, testes and the skin in center field of each projection were studied. A-radiation analog dosimetry system (RANDO) phantom with thermoluminescent dosimeters (ILD200) was used for the study. All of the exposure parameters were fixed. The total filtration was 2 mm Al equivalent. The column collaboration was 6 cm in diameter and 20 cm in length. The absorbed doses of organs were measured three times in each projection of the full-mouth series (FMS) exposures. RESULTS: The absorbed dose of lenses in FMS (249 microGy) in present study was much less (10%) than the doses (2,630 microGy) reported in 1976. The doses absorbed of other organs in the present study were thyroid gland (125 microGy), pituitary gland (112 microGy), parotid gland (153 microGy), submandibular gland (629 microGy), sublingual gland (1,900 microGy), and breast gland (12 microGy). The doses of the ovary and testis were to small to further analysis. CONCLUSION: All of the results show that the radiation risk to patients in intraoral radiograph has been reduced significantly. In the pituitary, half of the dose is from both sides of the maxillary molar projection. For the lenses, the largest contribultions of radiation (60%) come from the ipsilateral molar and premolar projection of maxilla. In parotid gland, up to 57% of the dose is from the contralateral molar, pre-molar and canine of maxilla. It could be derived that about 90% of the absorbed doses could be avoided in FMS if the column collimator is 20 cm long and the filter is 2.0 mm thick. If we use the 10-film complete mouth radiograph instead of the 14-film series, more 20% of the doses would be reduced. PMID- 11776539 TI - [Long-term effectiveness of arthroscopic subsynovial sclerotherapy and suturing on recurrent dislocation of the temporomandibular joint]. AB - OBJECTIVE: To evaluate long-term effect of arthroscopic surgery on recurrent mandibular dislocation. METHODS: 30 patients with 34 involved temporomandibular joints (TMJs) (26 unilateral, 4 bilateral) were treated by arthroscopic subsynovial sclerotherapy with or without a discal traction suture. Of them, four patients with 4 TMJs were undergone repeat arthroscopic operations. In total, 38 operations were performed in 34 TMJs. After arthroscopic lysis, lavage, and manipulation, the subsynovial sclerotherapy was performed with 5% sodium morrhuate and was located at retrodiscal lamina. Suturings were taken simultaneously in 19 cases, others (n = 19) were not sutured. The total amount of 5% sodium morrhuate was from 0.4 to 1.2 ml, and the numbers of injection points were from 2 to 5, and the subsynovial depth of injection was not more than 5 mm. The follow-up was from 1 mon to 8 years. RESULTS: The total success rate was 97% (33/34). There were 21 patients with 22 involved TMJs whose follow-ups were more than 2 years. The mean follow-up was 4 years (2-8 years). The long-term success rate was 95% (21/22). There were no serious complications. CONCLUSION: The long term effectiveness of arthroscopic sclerotherapy and suturing on recurrent mandibular dislocation is stable. PMID- 11776540 TI - [Pathologic study on synovial fluid after intra-articular corticosteroid therapy in temporomandibular joint disorders]. AB - OBJECTIVE: To study what happens after intra-articular injection of corticosteroid. METHODS: Synovial fluid after intra-articular corticosteroid therapy in temporomandibular joint disorders (TMD) was studied by hematoxylin eosin, PAS, and Atcian blue staining. RESULTS: The results were that broken synovial membrane and articular cartilage, lots of synovial lining cells, macrophagocytes, inflammatory cells and free cartilage matrix could be found in the lavage fluid. CONCLUSION: The results suggest that drug synovectomy may be one mechanism about intra-articular corticosteroid therapy in TMD, and this therapy could lead to progressive degradation and destruction of the articular cartilage. Arthrocentesis and lavage are needed three to five days after this therapy. PMID- 11776541 TI - [Color differences between a resin cement and try-in paste]. AB - OBJECTIVE: This study was to measure the color coincidence and difference of resin cement and its try-in paste. METHODS: 3 shades of a resin cement and its try-in paste were measured and analyzed by CIE L*a*b* on a reflection spectrophotometer. RESULTS: For shade 200, vulue of delta E* was less 1.4 in comparison between try-in paste and self-cured resin. CONCLUSION: The try-in paste of shade 200 matched the self-cured resin cement very well, but the try-in paste was lighter and more yellow than the light-cured resin cement. The resin cement of shade 100 was darker and more yellow than try-in paste; resin cement of shade 300 was lighter and more yellow than try-in paste. PMID- 11776542 TI - [Experimental study on the osteoradionerosis of jaw model of dogs with vascular corrosion casting]. AB - OBJECTIVE: To study pathologic alterations of mandibular microvascular system in osteoradionecrosis of jaws (ORNJ) in order to disclose its pathologic mechanism. METHODS: The right maxillofacial regions of 10 dogs were exposed to cobalt-60 radiation with a total dose of 60-80 Gy and dental extraction were performed at 3, 6 months after radiation. The ORNJ was diagnosed by gross observation, X-ray film and histopathologic examination. Then, the vascular corrosion castings of jaws were implemented and investigated. RESULTS: At 12 months after radiation, 7 cases of ORNJ occured. It was discovered on the casting specimen that the continuity of inferior alveolar arteries remained intact except one case where the artery was obliterated due to lesion involvement. There were defects of vascular networks in the necrotic area with irregular capillaries proliferating in the periphery of lesions and around the inferior alveolar arteries, where x ray examination showed new bone formation. CONCLUSION: Based on the experimental evidences, a new concept of pathogenesis of ORNJ is put forward: following the formation of "3-hypo" structures, local trauma-repairing process might induce capillary proliferation which bring about a large amount of mitotic death of endotheliocytes, the microcirculation failure takes place leading to ORNJ eventually. PMID- 11776543 TI - [Development in 50 years and challenges of the coming century]. PMID- 11776544 TI - [Present situation and prospects of tuberculosis control in China]. PMID- 11776545 TI - [Effects of relative imbalance between endothlin-1 and nitric oxide on pathogenesis of the ascaris-induced asthma in dogs]. AB - OBJECTIVE: To investigate the effects of relative imbalance between endothlin-1 (ET-1) and nitric oxide (NO) on pathogenesis of the ascaris-induced asthma in dogs. METHODS: Allergy induced asthma in dogs was established by inhaling ascaris antigen via an ultrasonic neblizer. At first, effects of ET-1 on respiratory system resistance (Rrs) and compliance (Crs) were studied in asthmatic dogs. Then, the roles of ET-1 and NO in regulating airway hyperresponsiveness (BHR) of asthma were investigated. Finally, effects of ET-1 on airway smooth muscle proliferating were observed. RESULTS: After intravenous injection of ET-1, there was a significant maximal increase in Rrs with (14.33 +/- 0.53) mm Hg.L-1.s-1 in normal dogs and (30.75 +/- 3.38) mm Hg.L-1.s-1 (P < 0.05) in asthmatic dogs. Also, there was a significant maximal decrease in Crs with (24.9 +/- 1.2) L/mm Hg in normal dogs and (14.8 +/- 0.9) L/mm Hg (P < 0.05) in asthmatic dogs. The dose dependent bronchoconstriction in dogs was induced by three different doses of ET 1 (0.25, 0.5, 1.0 microgram/kg). ET-1 dose-response curve was significantly shifted upward by L-NMMA (P < 0.05). This effect was inhibited by L-arg (P < 0.05). Histological studies showed that ET-1 can stimulate airway smooth muscle proliferating and thickening after one week of ET-1 (4.0 micrograms/kg) i.v. administration. CONCLUSIONS: ET-1 might be involved in BHR that may be associated with immediate asthma response (IAR) in asthmatic dogs. ET-1 may be important for airway remodeling. The relative imbalance between ET-1 and NO may contribute to pathogenesis of asthma. PMID- 11776546 TI - [Effects of nitroglycerin on nitric oxide and endothelin derived from bronchial epithelial cells and alveolar macrophages in asthma]. AB - OBJECTIVE: To investigate the changes of nitric oxide(NO) and endothelin(ET) derived from alveolar macrophages(AM) and bronchial epithelial cells (BEC), and the influences of nitroglycerin (NTG) on ET and NO in asthma. METHODS: BEC and AM from 15 patients with asthma exacerbation and 7 healthy control subjects were isolated and cultured for 48 hours. NO and ET levels in supernatants and expressions of iNOS-mRNA and ET-mRNA from cultured BEC and AM were examined by copper coated cadmiunm reduction, radioimmunoassay and in situ hybridization. RESULTS: The NO level and the ET level in supernatants, and expressions of iNOS mRNA and ET-mRNA from BEC and AM of the untreated group were higher than those of other groups (P < 0.05, respectively); The NO level from BEC and AM in supernatants of NTG pretreated group were elevated significantly and the ET level and the expression of iNOS-mRNA and ET-mRNA were lower than those of asthma untreated group (P < 0.05, respectively); The NO, ET levels and expressions of iNOS-mRNA, ET-mRNA derived from AM were higher than those derived from BEC in patients with asthma (P < 0.05, respectively); expression of iNOS-mRNA from BEC and AM were negatively correlated with the NO level in supernatants of cultured BEC and AM from the group pretreated by NTG in asthma (r = -0.60, r = -0.59; P < 0.01). While the expression of iNOS-mRNA and ET-mRNA by BEC and AM from other groups were positively correlated with the NO level and the ET level in supernatants of BEC and AM in asthma (all r > or = 0.902; P < 0.01, respectively). CONCLUSIONS: BEC and AM from patients with asthma exacerbation secreted a large quantity of NO and ET because of the increased expressions of iNOS-mRNA and ET-mRNA; AM was the main source of elevated NO and ET in airways of patients with asthma exacerbation. NTG directly enhanced the production of NO and significantly inhibited the expression of ET-mRNA, and therefore decreased the production of ET. PMID- 11776547 TI - [The effect of gancao on glucocorticoid receptors in chronic obstructive pulmonary disease]. AB - OBJECTIVE: To study the effect of gancao and glucocorticoid on glucocorticoid receptors. METHODS: The number of GCR of peripheral blood leukocytes was determined and FEV1% was assessed in 45 COPD patients and 10 control subjects. RESULTS: GCR was significantly lower in COPD patients during acute attack than in control subjects while F and ACTH were significantly higher (P < 0.001). In gancao, glucocorticoid and combination of gancao and glucocorticoid treated groups FEV1% was higher after treatment, especially in the combination group(P < 0.001). Gancao induced up-regulation of GCR while glucocorticoid induced down regulation of GCR, but combination of gancao and glucocorticoid had no effect on GCR. CONCLUSIONS: Gancao might reverse the down-regulation of glucocorticoid on GCR, thus enhance and prolong the effects of glucocorticoids. PMID- 11776548 TI - [The study of oxygen-conserving nasal cannula and evaluation of it's oxygen saving ratio in treatment]. AB - OBJECTIVE: To study the oxygen-conserving nasal cannula(CNC), and to evaluate it's oxygen saving benefit ratio in COPD patients. METHODS: (1) CNC was designed as a device which conserved oxygen during exhalation and given oxygen during inhalation; (2) Evaluation of the effect of oxygen therapy: blood analysis was measured at different flows of oxygen (0.5, 1.0, 1.5, 2.0 L/min) before and after oxygen therapy. The test is randomized; Oxygen saturation(SPO2) was measured at 1, 2, 3, 5, 10, 15, 30, 60, 120 minutes by pulse oximeter; (3) Evaluation of the oxygen saving benefit ratio: SPO2 was measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 L/min using CNC, the standard nasal cannula (SCN) and the new CNC. RESULTS: (1) During two hours of oxygen therapy, the values of PaO2 and SaO2 in the CNC group were always higher than those in the SNC group (P < 0.05); (2) When the supply flow to CNC was set at 0.5 L/min, 1.0 L/min, 1.5 L/min, 2.0 L/min seperately, the oxygen saving benefit ratio of CNC to SNC was 2.6:1, 1.8:1, 1.8:1 and 1.5:1 respectively. (3) The oxygen saving benefit ratio was comparable between CNC made in China and that made in foreign country. CONCLUSIONS: It was confirmed that CNC saved oxygen at different flows of oxygen, and the oxygen saving benefit ratio was higher at lower flows than that at higher flows. PMID- 11776549 TI - [Study on susceptible risk factors for COPD in smokers]. AB - OBJECTIVE: To explore the susceptible risk factors for COPD in smokers. METHODS: 154 patients with COPD (FEV1/FVC < 70%) were recruited as the case group whose smoking index (average cigarettes a day times smoking years) was > or = 300 and there was no complaint of chronic respiratory symptoms. The control group included 154 smokers pair-matched in age(+/- 3 years) gender, residence, absence of COPD (FEV1/FVC > or = 75%) and respiratory symptoms. 23 never-smoking subjects with FEV1/FVC > or = 75% and no respiratory symptoms served as healthy control. The following parameters were evaluated: questionaire, physical examination, ECG, chest X-ray, lung function test, methacholine provocation test of bronchial responsiveness and serum levels of elastase activity, alpha 1-AT activity, MDA, PIIIP, IgE and IgG. RESULTS: The positive rate of bronchial hyperresponsiveness was 78% in the case group, PC20 = (1.4 +/- 1.6) g/L; but 28% in the matched group were positive, PC20 = (2.7 +/- 2.3) g/L, (P < 0.001). No one was found hyperresponsive in the healthy control group. There were no differences in serum PIIIP and IgE between the case and the control groups, but they were markedly higher than those in the healthy control. Serum alpha 1-AT activity, room condition, occupational exposure, smoking habit (deep inhalation), cigarettes with or without filter tip, parents with bronchitis and(or) emphysema history, brothers or sisters with bronchitis history were correlated with COPD, OR being 2.33, 2.00, 1.64, 1.88, 1.76 and 3.67, respectively. Logistic regression revealed that alpha 1-AT activity, bronchial hyperresponsiveness, room condition and occupational exposure, smoking habit and respiratory disease history in family were related to COPD. CONCLUSIONS: alpha 1-AT deficiency may be a risk factor for COPD susceptible smokers. There may be relationship between bronchial hyperresponsiveness and developing COPD, but whether it is the cause or result of COPD needs further study. Smoking may induce elevation of serum PIIIP and IgE, but both of them are not directly related to COPD. Room condition, occupational exposure, smoking habit, and respiratory disease history in family may be associated with COPD in smokers. PMID- 11776550 TI - [The expression and regulation of heme oxygenase-1 in asthmatic guinea pigs]. AB - OBJECTIVE: To explore the expression and pathogenic mechanism of heme oxygenase 1(HO-1) in asthma. METHODS: Two groups of guinea pigs (10 in each) were treated with the specific stimulator(hemin) and inhibitor(Sn-PP) of HO-1 respectively. Their effects on the levels of HO-1 activity, COHb, cGMP and IgE in serum or blood and lung tissues were compared with each other. Acute asthmatic group (AAG), dexamethasone-prevented group(DPG), stable asthmatic group, ovalbumin sensitized group and normal control group(NCG) were also included. Lung tissues of tested animals were pathologically observed and immunohistochemically stained. RESULTS: In the AAG and hemin stimulated group, the levels of COHb, cGMP and IgE were significantly increased with higher levels of activity and expression of HO 1 protein compared with the NCG (t = 4.575-10.188, P < 0.01). In DPG and Sn-PP inhibited groups, however, all measured parameters were markedly reduced compared with the AAG(P < 0.01). The other groups were normal. CONCLUSIONS: The increased production and activity of HO-1 resulted in increases of endogenous CO and cGMP and promoted inflammation and immunoreaction in asthma. PMID- 11776551 TI - [The role of apoptosis and Fas/FasL in lung tissue in patients with acute respiratory distress syndrome]. AB - OBJECTIVE: To evaluate the effects of apoptosis and expression of apoptotic related genes on acute respiratory distress syndrome (ARDS). METHODS: Nine patients with ARDS and 5 non-ARDS patients were included. By using TUNEL, histopathology and immunocytochemistry techniques, apoptosis and Fas, FasL protein expression were studied in patients with ARDS in acute stage and in control subjects. RESULTS: Apoptosis ratio was significantly higher in lung tissues in the patients with ARDS than in those of control subjects, especially in alveolar epithelial cells and pulmonary vascular endothelial cells. Fas, FasL protein expression were up-regulated in lung tissues of patients with ARDS. There was a significant correlation between expression of Fas, FasL and ratio of apoptosis. CONCLUSIONS: During the acute stage of ARDS, increase of apoptosis ratio in alveolar epithelial cells and pulmonary vascular endothelial cells, and activation of Fas/FasL system may contribute to the pathogenesis of this syndrome. PMID- 11776552 TI - [Clinical significance of different mycobacterial antigens in diagnosis of tuberculosis]. AB - OBJECTIVE: To evaluate the significance of different mycobacterial antigens in diagnosis of tuberculosis. METHODS: The sensitivity and specificity of 5 mycobacterial recombinant proteins in diagnosis of tuberculosis were observed by using ICT-TB card and the results of ICT-TB card were compared with PPD skin test and LAM. RESULTS: The sensitivities of ICT-TB card, LAM and PPD skin test in diagnosis of pulmonary tuberculosis were 55.9%, 52.6% and 75.0% respectively. There was statistically significant difference between the latter and the other two (P < 0.05). The specificities of ICT-TB card, LAM and PPD skin test in diagnosis of pulmonary tuberculosis were 87.6%, 62.9% and 68.9% respectively. There was statistically significant difference between the former and the other two. The clinical positive predictive value in diagnosis of pulmonary tuberculosis was 88.5%; the clinical negative predictive value was 53.8%. The positive reactions of ICT-TB in non-tuberculosis were caused mainly by antigens 4, 5, and if antigens 4, 5 were excluded, the specificity of ICT-TB card rose to 98.9%. CONCLUSIONS: The results suggested that measuring mycobacterial recombinant proteins was a useful supplementary tool for diagnosis of pulmonary tuberculosis. PMID- 11776553 TI - [Transferring of mdr1 gene into murine bone marrow cells and its protective effects on hematopoietic cells against toxicities of anticancer agent]. AB - OBJECTIVE: To investigate the protective effects of mdr1 gene on hematopoietic cells against anticancer agents and to explore an effective approach to prevent myelosuppression due to chemotherapy. METHODS: mdr1 gene was transferred into murine bone marrow cells with plasmid pHaMDR1/A by the mediation of lipofection. Pgp, a product of mdr1 gene expression, and its function were detected by flow cytometry, immunohistochemistry, and rhodamine test respectively. Also, the resistance of transferred murine bone marrow cells to anticancer agents was tested by colony-forming unit test after exposure to anticancer agents and by bone marrow transplantation murine model. RESULTS: mdr1 gene was successfully transferred and expressed in bone marrow cells. Transferred murine bone marrow cells were resistant to anticancer agents both in vitro and in vivo. CONCLUSIONS: Transfection of mdr1 gene into hematopietic cells can protect bone marrow cells against the toxicities of anticancer agents. PMID- 11776554 TI - [Replacement of the superior vena cava with vascular prosthesis in surgical treatment of lung carcinoma]. AB - OBJECTIVE: To investigate the effect, surgical technique and prognosis of replacement of the superior vena cava(SVC) with vascular prosthesis in surgical treatment of advanced lung carcinoma. METHODS: Twenty six patients with right lung carcinoma invading the SVC (central lung carcinoma in 21 cases, peripheral lung carcinoma in 5 cases) underwent radical resection of tumor with concomitant replacement of SVC with vascular prosthesis. All patients took a low dose of anticoagulant in short-term after operation. Long-term follow-up was conducted. RESULTS: All the cases had no intraoperative or postoperative early death, and no early or late obstruction of SVC. Follow-up was conducted in 23 cases. The overall survival rates at 1, 3 and 5 years were 85%(22/26), 39%(7/18) and 36%(4/11) respectively. CONCLUSIONS: Combination of resection of tumor and replacement of SVC enabled some cases of advanced lung carcinoma to achieve complete resection. This surgical technique extended the indications of surgical treatment of lung carcinoma, and increased the survival rate of advanced lung carcinoma. Further clinical applications are recommended. PMID- 11776555 TI - [The isolation and drug susceptibility of penicillin resistant Streptococcus pneumoniae in Guangzhou]. AB - OBJECTIVE: To investigate the isolation rate and drug susceptibility of PRSP in Guangzhou and in vitro antimicrobial activities of 8 antimicrobial agents against PRSP. METHODS: MICs were tested by E-test. RESULTS: Of 102 strains of Streptococcus pneumoniae, 12 strains were low-level resistant against penicillin (isolation rate 11.8%) and the antimicrobial activites of 5 drugs (augmentin, cefaclor, ceftriaxone, cefuraxime, ofloxaxin) against them were within their MICs, augmentin and ceftriaxone being the most powerful. They were resistant to azithromicin, oxacillin and penicillin. CONCLUSIONS: The isolation rate of Penicillin resistant Streptococcus pneumoniae was not high in Guangzhou, but it may increase with the extensive use of antimicrobial agents, which deserves much attention. PMID- 11776556 TI - [The changes of NO2-./NO3-. level in sputum from patients with asthma and their clinical implications]. AB - OBJECTIVE: To evaluate the clinical applications of the detection of the stable end products of NO, nitrite and nitrate (NO2-./NO3-.) in sputum from patients with asthma. METHODS: 45 patients with asthma at remission (group I, n = 15) or exacerbation state with mild attack (group II, n = 15) or moderate to severe attack (group III, n = 15), 15 cases of chronic cor pulmonale secondary to chronic bronchitis at exacerbation (group IV), and 20, normal control subjects (group V n = 20) were included in this study. NO2-./NO3-. in sputum and serum were measured by Griess reaction, while the eosinophil cationic protein (ECP) in sputum and pulmonary function were also measured in tested patients with asthma. RESULTS: The median concentrations of sputum NO2-./NO3-. in group I, II and III were 85, 131 and 136 mumol/L respectively, all were significantly higher than that in controls (63 mumol/L); those of group II and III were significantly higher than that of group I, while that of group IV (33 mumol/L) was significantly lower than those of the asthmatic groups and the control. The level of NO derivatives in sputum was closely correlated with the degree of airflow obstruction and sputum ECP levels in patients with asthma at remission (r = 0.587, P < 0.05; r = 0.535, P < 0.01 respectively) and exacerbation (r = -0.485, P < 0.05; r = 0.563, P < 0.05 respectively). There was no significant correlation between serum and sputum NO2-./NO3-., and no significant correlation between serum NO2-./NO3-. and the degree of airflow obstruction. A significant decrease in the concentration of sputum NO2-./NO3-. was observed after therapeutic treatment of patients with moderate to severe attack (136 vs 93 mumol/L). CONCLUSION: The level of NO2-./NO3-. in sputum may be a useful marker for monitoring the state of airway inflammation and assessing the therapeutic efficacy. PMID- 11776557 TI - [Effect of anti-CD4+ human/murine chimeric antibody on the proliferation and apoptosis of lymphocyte in patients with asthma]. AB - OBJECTIVE: To investigate the effects of anti-CD4+ human/murine chimeric antibody on the proliferation and the apoptosis of peripheral blood lymphocytes (PBL) in patients with asthma. METHODS: PBL isolated from patients with asthma were cultured with 50 mg/L, 100 mg/L anti-CD4+ human/murine chimeric antibody and anti CD3+ McAb (10 mg/L) for 0, 24, 48 h in vitro, the apoptosis cell percentage were detected by flow cytometry and in situ end-labeling technique of fragmental DNA as well as the proliferation of PBL were detected by MTT method. RESULTS: Comparing with normal controls, the apoptosis cell percentage was significantly decreased by stimulation with anti-CD3+ McAb for 24 h and 48 h, the proliferation of lymphocyte was increased in patients with asthma; the apoptosis cell percentage of patients with asthma was significantly increased (P < 0.01, respectively) with the cell cultured with 50 mg/L or 100 mg/L anti-CD4+ human/murine chimeric antibody for 24 h or 48 h At the same time the lymphocyte proliferation was inhabited (P < 0.01, respectively). CONCLUSIONS: It is demonstrated that the proliferation of PBL in patients with asthma were increased and the apoptosis cell percentage were decreased, anti-CD4+ human/murine chimeric antibody had inhibited the proliferation of T lymphocyte and had enhanced the T lymphocyte apoptosis. The anti-CD4+ human/murine chimeric antibody may be potentially useful for the biotherapy of asthma. PMID- 11776558 TI - [The changes of protein kinase C activity in peripheral blood lymphocytes in asthmatic patients]. AB - OBJECTIVE: To investigate changes of protein kinase C (PKC) activities in peripheral blood lymphocytes (PBL) and the relationship between PKC activities and level of the air flow limitation in asthmatic patients. METHODS: PKC from cytosolic and membrane fractions of PBL was isolated and purified, then its activities were determined. RESULTS: (1) The total PKC activities in PBL in asthmatic subjects (n = 18) were significantly increased as compared to those in normal subjects (n = 6, P < 0.01). More over, the membrane PKC activities and their percentages in the total PKC activities were higher in asthmatics than in normals (P < 0.05). In vitro it suggested that methacholine(n = 5) or histamine (n = 5) could significantly increase translocation of PKC from cytosol to membrane (P < 0.05) and, by doing so, activate the PKC in PBL. (2) The total PKC activities were significantly correlated with FEV1% (r = -0.73, P < 0.001, n = 18), PEF(r = -0.62, P < 0.01, n = 18) and V50 (r = -0.63, P < 0.01, n = 18). (3) The total PKC activities in PBL were significantly correlated with the levels of sIL-2R in serum in the asthmatics (r = 0.58, P < 0.05, n = 18). CONCLUSIONS: (1) The total activities and the level of translocation of PKC were significantly increased in PBL in asthmatics as compared to normals. This abnormal activation state of PKC in PBL may be related with the increased levels of inflammatory mediators. (2) Highly significant correlations existed between the total PKC activities and the level of air flow limitation in asthmatics. (3) PKC signal pathway may be implicated in the activation of T-lymphocytes in asthma. It is suggested that the role of PKC signal pathway may be important in the pathogenisis of asthma. PMID- 11776559 TI - [Study of 6 cases of AIDS with pulmonary complication]. AB - OBJECTIVE: To improve and to increase the awareness of pulmonary complications of AIDS. METHODS: Six cases of confirmed AIDS from may 1992 to August 1997 were analyzed. RESULTS: Of the six cases, there were five complicated with pneumocysitis carinii pneumonia (PCP) (in which one had PCP as the first occurred manifestation). The clinical presentations of PCP were fever(5/5), dyspnea on exertion or at rest(4/5), and hypoxemi with mean PaO2 of 58.1 mm Hg. Chest X-ray showed bilateral diffuse interstitial or alveolar infiltrates. Pulmonary tuberculosis, tuberculous lymphadenities (fast-acid staining positive but PPD negative) and bronchial fungal infection were found in three cases. CONCLUSIONS: AIDS patients are at high risk of suffering from pulmonary complications, of which PCP is more common. If young pateints who were healthy in the past suddenly suffered from pneumonia and respiratory failure, PCP should be considered. When opportunistic pulmonary infections are diagnosed under special circumstances, one should be alert to the possibility of AIDS. In these cases serum HIV antibodies should be checked immediately. PMID- 11776560 TI - [The relationship between hypoxic pulmonary hypertension and changes of HO-1 and its mRNA]. AB - OBJECTIVE: To study the relationship of HO-1 and HPH. METHODS: The expression of HO-1 and HO-1 mRNA were observed in pulmonary vessles of rats using the technique of immunohistochemistry and hybridization in situ. The average value of integral light density of HO-1 in three different diameters of arteries was detected by means of the image analysor and considered as the relative content in pulmonary arteries. RESULTS: Hypoxia induced the expression of HO-1 and HO-1 mRNA and the relative content of HO-1 was significantly increased in pulmonary arteries corresponding with the period of hypoxia. CONCLUSIONS: In the condition of HPH, relative content of HO-1 increase obviously. It suggests that HO-1 plays certain role in development of HPH. The change of HO-1 mRNA expression is the basis of molecular change of HO-1. PMID- 11776561 TI - [Chronic obstructive pulmonary disease and pulmonary structural remodeling]. AB - OBJECTIVE: To understand the pathological characteristics of the lungs in 20 autopsy cases of chronic obstructive pulmonary disease(COPD) complicated with cor pulmonale and its relationship with structural remodeling of the lungs. METHODS: The lungs of 20 autopsy cases of COPD complicated with cor pulmonale were fixed in 10% formalin or by low pressure 18.4-33.4 mm Hg perfusion with 10% formalin. The lungs were cut sagitally into large slices with 2 cm in thickness, and the percentage of the emphysematous areas was calculated by point counting. The pathological characteristics of bronchioles and the stromal fibrosis area were examined microscopically and quantitatively using a latticed micrometer (Zeiss). The distribution and the ratio of type I to type III collagen in the lung tissue were determined using a sirius red-polarizing microscopy-morphmetry method. RESULTS: Of the 20 cases of COPD, irregular and saccular emphysema were the most frequent (17/20). 10 cases had moderate and high degree of emphysema, and 6 cases showed hypertrophy of the right ventricle (heart weight > 400 g). The mean area of stromal fibrosis auounted for total area of the examined lungs was (27.1 +/- 2.9)% and control group (12.0 +/- 1.8)%. The ratio of the area of the type I collagen to type III collagen was 5.6:1 (control group 1.3:1). All 1504 bronchioles showed chronic inflammation, 38% of which revealed acute exacerbation, and 53% of which showed lumen stenosis and fibrotic obstruction. CONCLUSIONS: Acute and chronic bronchiolitis and peri-bronchiolitis are the essential pathological changes in COPD, and also are the key link of the structural remodeling of the pulmonary tissue and vessels. PMID- 11776562 TI - [Clinical analysis of combination therapy for 252 patients of lung cancer with brain metastasis]. AB - OBJECTIVE: To evaluate the efficacy of combination therapy and prognostic factors for lung cancer patients with brain metastasis. METHODS: The survival time and survival rates with various therapeutic methods were analyzed retrospectively in 252 patients with brain metastasis. RESULTS: The median survival time and 1, 2 year survival rates in surgery and X-knife plus radio-chemotherapy group and combination therapy of radiotherapy with chemotherapy were significantly longer than radio-chemotherapy alone group (P < 0.01 and P < 0.05); the pathological type of lung cancer did not affect the survival time and survival rate (P > 0.05); the survival time and survival rate of single brain metastasis (median survival time was 8.5 months 1, 2 year survival rates were 35% and 11% respectively) and non-extrabrain metastasis (8.5 months, 29%, 8%) were much longer than multiple brain metastasis and extrabrain metastasis (P < 0.01); the 1 year survival rate of older patients(> or = 50 years, 29%) were significantly higher than younger ones (< 50 years, 15%) (P < 0.05). CONCLUSIONS: Combination therapy of surgery and X-knife plus radio-chemotherapy are better than radio chemotherapy alone for brain metastasis of lung cancer, severity of metastasis and patients' age are the prognostic factors. PMID- 11776563 TI - [Changes in blood coagulation affected by rifampicin administration]. AB - OBJECTIVE: To study the characteristics of influence on coagulation by rifampicin (RFP) administration. METHODS: Seventy-three patients, ages between 10 and 65 years(mean age 30.3 years), with tuberculosis of neck lymphnode were treated with 2HRZS/10HRE. The prothrombin time, activity, fibrinogen, II: C, V: C, VII: C, IX: C and alanine aminotransferase concentration in each case were observed during the period of RFP administration. RESULTS: The prolongation of the PT and the reduction of the PA, FIB concentration in 48 cases were observed after 5-30 days following RFP administration. These changes depended on drug dosage and duration, especially the severe influence on coagulation were detected when the RFP were reused after the ALT normalized in seventh to tenth months. The ALT was (18 +/- 12) U/L in the tenth month, but the PT was (19.2 +/- 3.9) s and the FIB was (1.8 +/- 0.5) g/L respectively. CONCLUSIONS: Not only the coagulation factors II, VII, IX, X, but also I V, VI and VIII were affected by RFP. The coagulation test is more sensitive than ALT test in the evaluation of liver injury. RFP should be stopped when FIB less than 1 g/L in spite of ALT in normal range. PMID- 11776564 TI - [Quantitative detection of Mycobacterium tuberculosis DNA in peripheral blood from patients with pulmonary tuberculosis by AmpliSensor-PCR technique]. AB - OBJECTIVE: To evaluate the clinical value of the quantitative detection of Mycobacterium tuberculosis DNA by Amplisensor-PCR in peripheral blood from patients with pulmonary tuberculosis. METHODS: The model of Mycobacterium tuberculosis DNA in blood was made by QIAamp and AcuPure methods, quantitative detection of Mycobacterium tuberculosis DNA by AmpliSensor-PCR technique and the results were compared with IS6110 single-tube nested PCR (SN-PCR). RESULTS: The peripheral blood from 200 patients with pulmonary tuberculosis were detected respectively by using AmpliSensor-PCR and IS6110 SN-PCR methods. The positive rates of Mycobacterium tuberculosis DNA were 60.5% and 63.5% respectively, and that from 85 patients with non-pulmonary tubeculosis were 4.7%, 8.2%. CONCLUSIONS: AmpliSensor-PCR method showed higher sensitivity and specificity in detecting the Mycobacterium tubeculosis DNA from peripheral blood. The variation of the TB-DNA may be useful in evaluating the prognosis of the patients. PMID- 11776565 TI - [Mechanism of growth inhibition by genistein of human breast carcinoma]. AB - OBJECTIVE: To study the mecnanism of inhibition of breast carcinoma cells by genistein. METHODS: Human breast cancer cell lines were treated in vitro with genistein. Northern blot, Western blot, plasmid transfection and apoptosis assay were used to evaluate the mechanism of cell growth inhibition. RESULTS: Genistein could inhibit proliferation of human breast carcinoma cells with different ER status and p53 status. This inhibition was associated with induction of p21WAF1/CIP1 mRNA and protein expression. Exposure of MCF-7 and MDA-MB-231 cells to genistein resulted in statistically significant increased p21WAF1/CIP1 mRNA stability, accompanied with increased p21WAF1/CIP1 protein expression. This increase in p21WAF1/CIP1 was subsequently followed by the onset of apoptosis. CONCLUSION: The inhibitory effect of genistein on cell proliferation of breast cancer appears to be due to p21WAF1/CIP1 expression and apoptosis through mechanism independent of ER and p53. The results provide evidence for the potential usefulness of genistein in the prevention and treatment of human breast cancer. PMID- 11776566 TI - [Characteristics of expression of CD44v and receptor for HA-mediated motility (RHAMM) in multi-step gastrocarcinogenesis]. AB - OBJECTIVE: To explore the potential significance of expression of CD44 and RHAMM at different stages of gastric carcinogenesis. METHODS: The expression pattern of CD44 and RHAMM in non-cancerous mucosa, preneoplastic lesions and carcinomas of the stomach was examined by RT-PCR, Southern blot hybridization, immunohistochemical staining and Western blot hybridization. RESULTS: Expression of CD44 v5 could be observed not only in cancers, but also in pre-neoplastic and non-cancerous specimens. CD44 v7 was commonly seen in non-cancerous lesions but its expression tended to decrease with the progression of pre-malignant phenotype. CD44 v8-v10 could only be observed in some intestinal metaplasia, dysplastic proliferation and undifferentiated carcinoma. Nevertheless, CD44 v6 was found exclusively in cancer tissues, with a positive rate of 14%. The frequency of RHAMM detection was about 10% in non-cancerous mucosa but tended to increase with tumor development, reaching an average of 74% in gastric cancers. In 80% of the invading cancer cells, RHAMM and CD44v coexpressed, or complementarily expressed. CONCLUSION: Expression of RHAMM is more associated with progression of gastric malignancy. Irrespective of its low frequency, CD44 v6 is still a reliable marker of malignant transformation of gastric mucosa. Co expression or complementary expression of CD44v and RHAMM might facilitate invasion and metastasis of gastric cancer. PMID- 11776567 TI - [Combination therapy of murine liver cancer with IL-12 gene and HSV-TK gene]. AB - OBJECTIVE: To investigate the synergistic antitumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. METHODS: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV/TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2 x 10(5) MM45T. Li Cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T. Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected i.p. (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. RESULTS: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK + GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significanty in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+ T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. CONCLUSION: Combination therapy with IL-12 gene and HSV-TK gene + GCV is effective for mouse liver cancer. PMID- 11776568 TI - [Experimental study of adhesion of gastric cancer cells to the peritoneum]. AB - OBJECTIVE: To identify factors in favor of tumor cell adherence to the peritoneum. METHODS: Pieces of peritoneum from BALB/c mice were collected and incubated in vitro in the presence of human gastric cancer MGC-803 cells. Cells adhered to the peritoneum was assessed by MTT staining. The result was expressed as the percentage of tumor cells adhered (AD). RESULTS: If the peritondum had been previously injured, either by scraping or exposure to air, AD was significantly more than that of the control (P < 0.01). AD was significantly increased as compared to the control when the peritoneum was cultured in the presence of white cells, platelets, plasma or CEA. CONCLUSION: Adhesion of cancer cells to the peritoneum may be facilitated by peritoneal injury, and the presence of normal blood constituents. Oncofetal antigen with adhesive property such as CEA also helps tumor cells adhere to the peritoneum. The likelihood of post operative peritoneal metastasis can be minimized if care has been taken to protect the peritoneum from injury and to thoroughly wash the peritoneal cavity before the abdomen is closed. PMID- 11776570 TI - [Radioimmunodetection of human trophoblastic cancer xenograft in nude mice]. AB - OBJECTIVE: To study the efficiency of radioimmunodetection to locate xenograft of human trophoblastic cancer in nude mouse. METHODS: Radioimmunodetection was performed with a cocktail of 131I-labeled mouse anti-hCG monoclonal antibodies to image xenogaft of human trophoblastic cancer in nude mice. Normal mouse IgG used to treat mice bearing trophoblastic cancer xenograft was used as control. Radioactivity in different tissues was measured and the tumor/non-tumor(T/NT) ratio was calculated. RESULTS: The accumulation of radioactivity in the xenograft could be recognized as early as 24 hours after the injection of the radiolabeled anti-hCG antibodies. Radioactivity accumulation became increasingly evident with time. At 72-96 hours after injection of the radiolabled antibodies, the xenograft could be clearly shown. The minimal size of the xenograft with demonstrable radioactively was 0.8 cm in diameter. The T/NT ratio increased with time and was obviously higher than that in mice treated with normal mouse IgG. CONCLUSION: Radioimmunodetection can efficiently locate human trophoblastic cancer xenograft in nude mice. PMID- 11776569 TI - [Gene detection and localization by FISH with short DNA fragment cloned in plasmid]. AB - OBJECTIVE: To establish a method of detecting and localizing newly cloned gene by FISH using short DNA fragment. METHODS: Bio-14-dATP was incorporated into the target gene cloned in plasmid by nick translation followed by conventional FISH with some modification. By Means of this method, c-met, c-erbB2, 1A6, APC and Rb genes were examined in ovarian and gastric cancer cell lines. RESULTS: 1A6, a newly isolated gene was located at the long arm of one of the C group chromosomes. Oncogene c-met, c-erbB2 and trmor suppressor gene APC, Rb were shown to produce clear-cut hybridization signals in ovarian and gastric cancer cells. CONCLUSION: Short DNA fragment cloned in plasmid is useful for studies of gene localization, gene deletion and amplification by FISH. PMID- 11776571 TI - [Direct chromosome analysis and FISH study of primary gastric cancer]. AB - OBJECTIVE: To investigate chromosome aberrations and their role in the genesis and progression of primary gastric cancer. METHODS: An improved, direct method of chromosome preparation from solid tumors was adopted for G-banding analysis followed by FISH on decolored G-banding chromosomes so that chromosome aberrations could be confirmed at DNA level. RESULTS: A total of 28 primary gastric cancer specimens were studied. Case 1 and case 2 had simple chromosome numerical changes: 49, XY, +2, +8, +9 and 47, XX, +8, +20, respectively. All but case 1 and 2 had complicated chromosome abnormalities. Structural changes of frequent occurrence involved del(7q) (21/26), del(3p)(14/26), del(1p)(11/26) and del(17p)(10/26). The chromosome abnormalities could be simple or complicated. In the former, numerical changes involving 1 to 3 chromosomes could be observed. Trisomies 8 and 9 appeared to be a cytogenetic subgroup of primary gastric cancer. In the latter, del(7q) was the most consistent structural aberration. The 7q32-qter was the commonly lost segment. CONCLUSION: Numerical and structural alterations of chromosomes are present in primary gastric cancer. Del(7q) is one of the structural changes characteristic of primary gastric cancer. In the 7q32 qter segment, a tumor suppressor gene probably exists and it may have close relation to the genesis and progression of gastric cancer. PMID- 11776572 TI - [Expression and clinical significance of telomerase catalytic subunit gene in lung cancer and its correlations with genes related to drug resistance and apoptosis]. AB - OBJECTIVE: To investigate mRNA expression and prognostic significance of telomerase catalytic subunit (hTRT/hEST2) and its relations to apoptosis, proliferation and drug resistance in patients with lung cancer. METHODS: Telomerase repeat amplification protocol-PCR(TRAP-PCR) and in situ hybridization were used to detect telomerase activity and expression of hTRT/hEST2 mRNA, respectively. The expression of bcl-2, c-myc, MRP, Neu, MDR1 at mRNA and protein levels was measured by means of RT-PCR and immunohistochemisty. In situ end labeling(ISEL) assay was used to evaluate apoptotic cells. RESULTS: hTRT/hEST2 mRNA was detected in 41 of 56 NSCLC(73.2%) and 17 of 20 SCLC(85.0%), but it was not expressed in lung tissues adjacent to the tumor. Telomerase activity was postively correlated with the expression of hTRT/hEST2. In NSCLC, hTRT/hEST2 mRNA was positively correlated with bcl-2(r = 0.7327, P = 0.015), c-myc(r = 0.8263, P = 0.001), MRP(r = 0.3971, P = 0.003) and neu(r = 0.3208, P = 0.017), but not with MDR1 (r = 0.2415, P = 0.672). In SCLC, positive correlation was only found between hTRT/hEST2 and bcl-2 (r = 0.5663, P = 0.024). Correlation was positive between hTRT/hEST2 mRNA and Ki-67 expression but negative between hTRT/hEST2 and apoptosis both in NSCLC and SCLC. Multivariate Cox regression analysis showed that telomerase catalytic subunit hTRT/hEST2 and number of apoptotic cells were of prognostic significance in NSCLC. CONCLUSION: As telomerase catalytic subunit expression shows correlations with MDR- and apoptosis-related genes and is of prognostic significance, telomerase in relation to multiple drug resistance deserves in-depth study. PMID- 11776573 TI - [Application and comparison of meta and pooled analyses in the study of cancer epidemiology]. AB - OBJECTIVE: To introduce two comprehensive methods of analysis, Meta and pooled, frequently used in cancer epidemiology, and to compare them with authentic examples. METHODS: From data of a multicenter case-control study of lung cancer risk factors among non-smoking females, "family history of lung cancer" and "smoking history of parents" were the two variables selected for analysis. Based on the data from individual centers, Meta and pooled methods were employed to perform comprehensive analysis and the results compared. In the former, both fixed and random effect models were considered. RESULTS: When the data from individual study centers were analyzed, odds ratios (OR) differed. The OR of variable "family history of lung history" was statistically significant in Shanghai, while that of variable "smoking history of parents" was statistically significant in Harbin. Given the fixed effect model, the results of analysis were identical under different conditions of analysis (non-adjusted, adjusted with Mantel-Haenszel methods and multivariate logistic analysis). The results were similar when random effect model was used. In case the fixed effect model was not valid and there were some differences obtained by the two methods, combined parameters calculated from random effect model would be used. Stratified logistic model seemed better than basic logistic model in the pooled analysis. CONCLUSION: The results from Meta and pooled comprehensive analyses are essentially consistent. PMID- 11776574 TI - [Multiple tumor suppressor 1/p16 gene alterations in human esophageal squamous cell carcinoma: clinical significance and regional difference]. AB - OBJECTIVE: To further understand multiple tumor suppressor 1/p16 (mts1/p16) gene alterations in squamous-cell esophageal carcinoma (EC) in relation to its biologic behavior and regional difference. METHODS: Samples of human EC from 92 patients residing in Zhejiang province and in Linxian, Henan province were analyzed for the expression, mutation and deletion of the multiple tumor suppressor gene (mts1/p16) by immunohistochemical staining, polymerase chain reaction and single strand conformation polymorphism. RESULTS: mts1/p16 expression at protein level was demonstrated in 44 cases (47.8%). Gene deletion was detected in 22 cases (23.9%) and point mutation in 5 cases (5.4%). Expression of mst1/p16 showed significant correlation with pathologic staging, lymph node status and survival. However, deletion of mst1/p16 did not show correlation with the clinico-pathologic parameters. EC patients in stage T2 from Linxian had significantly lower rate of mst1/p16 protein expression compared to those from Zhejiang province at the same time period. Moreover, there was close association between gene alterations (mutation + deletion) and frequency of lymph node metastasis in Zhejiang EC patients. No such association was observed in EC patients from Linxian. CONCLUSION: msts1/p16 gene alteration is a common genetic event in the carcinogenesis and progression of human esophageal cancer. EC patients from two different regions present differential alterations in mst1/p16 gene. PMID- 11776575 TI - [Post-operative staging and survival based on the revised TNM staging system for non-small cell lung cancer]. AB - OBJECTIVE: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1997. METHODS: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoracotomy from April 1969 through Dec. 1993. The end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. RESULTS: In this series, 30 patients (1.71%) were lost from follow-up. The 5-year cumulative survival rate was 88.0% for patients in stage IA, 53.9% in stage IB, 33.5% in stage II, 14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survival rate was 39.8%, 14.4% and 4.2% in patients treated with complete tumor resection, tumor debulking and exploratory thoracotomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0%, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathologic type of the primary tumor. CONCLUSION: The revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of M1 need to be further studied. PMID- 11776576 TI - [A comparative study between clinical response and pathologic changes to preoperative chemotherapy in non-small cell lung cancer]. AB - OBJECTIVE: To study the clinical response to preoperative chemotherapy in relation to pathologic changes in non-small cell lung cancer (NSCLC). METHODS: Forty-six stage I-IIIa NSCLC patients were given 1-2 courses of preoperative chemotherapy with mitomycin C (MMC) 6 mg.M-2 on day 1, vindesine (VDS) 2.5-3 mg.M 2 on day 1, day 8 and/or day 15, and cisplatin (DDP) 90 mg.M-2 on day 1 (MVP regimen). 'The treatment was recycled every 28 days. Clinical response was assessed according to WHO criteria. Pathologic changes of the resected tumor were categorized to 3 grades. Grade I: No tumor under gross and microscopic observation. Grade II: Grossly no tumor present but residual tumor cells under microscopic observation. Grade III: Tumor reduced in size with clear margins; marked tumor cells degeneration and necrosis accompanied with fibrosis. Grade IV: Active proliferation of tumor cells with invasion. Grade I-II was considered to be chemotherapeutically effective. RESULTS: (1) The clinical response rate was higher in patients who had received 2 courses than those received 1 course of treatment. More patients treated with 2 courses had their pathologic changes in Grade I-II than those treated with 1 course of chemotherapy but the response rate was not fully consistent with pathologic grading. (2) Pathologic grading significantly correlated with the extent of tumor involvement but not with the lymph node status. (3) Efficacy of chemotherapy should be evaluated jointly by the clinical response and grading of pathologic changes. (4) Chemotherapy with MVP regimen did not elicit severe toxic side effect. Nor did it lead to operative morbidity, operative mortality and a delay in postoperative recovery. CONCLUSION: Preoperative chemotherapy with MVP regimen is effective in the treatment of NSCLC in stage I-IIIa. PMID- 11776577 TI - [Arterial infusion chemotherapy combined with concurrent radiotherapy for local advanced pancreatic cancer]. AB - OBJECTIVE: To analyze the treatment results of un-resectable local pancreatic cancer by arterial infusion chemotherapy plus concurrent radiotherapy or radiotherapy alone. METHODS: A total of 50 patients with local advanced pancreatic cancer from January 1992 through October 1995 were treated either by arterial infusion chemotherapy (C) plus concurrent radiotherapy (R) (22 cases) or by radiotherapy alone (28 cases). Radiation given was the same in the two groups of patients (50-60 Gy in 5 to 6 weeks, 1.8-2 Gy/Fx, 5 Fx/wk). Infusion chemotherapy was performed once every 4 weeks, consisting of 5-fluorouracil 1.0 g, mitomycin C 10 mg, cisplatin 60 mg. An average of 2.3 cycles was given to each patient. RESULTS: Although the remission rate of jaundice and pain did not show significant difference between the two groups, patients in C + R treatment group had longer period of symptomatic remission (P < 0.05). The response rate (CR + PR) was 68.2% in C + R treatment group and 35.7% in R treatment group, respectively. The 1-, 2-, and 3-year survival rate was 75.3%, 36.8%, 25.4% in C + R treatment group, and 51.3%, 22.6%, 8.7% in R treatment group, respectively. CONCLUSION: Arterial infusion chemotherapy combined with concurrent radiotherapy is a treatment of choice for patients with local unresectable cancer of the pancreas. PMID- 11776578 TI - [Pylorus-preserving pancreatoduodenectomy--a report of 15 cases]. AB - OBJECTIVE: To prevent post operative disturbauce of gastric emptying by pylorus preserving pancreatoduodenectomy (PPPD). METHODS: 1. To preserve the vascular and nerve supply of gastric antrum, pylorus and duodenal bulb during operation. 2. To ensure long enough resection of duodenum from the pylorus. 3. To perform folding suture to shorten the hapatogastric ligament. RESULTS: In 15 cases of pancreatic and periampullar cancer so freated, neither residual cancer nor gastric emptying disorder was found after operation. The quality of life of the patients was improved. CONCLUSION: PPPD is a therapeutic choice for patients with pancreatic and peri-ampullar cancer. PMID- 11776579 TI - [Ultrasonic and CT diagnosis of large upper abdominal mass]. AB - OBJECTIVE: To assess accuracy of ultrasonic (US) and CT diagnosis of big mass in the upper abdomen. METHODS: Data from 38 clinically and pathologically confirmed cases were retrospectively analyzed and accuracy of their preoperative US and CT diagnosis compared. RESULTS: US diagnosis was correct in 3 of 9 (33.3%) cases with a mass in the liver, in 16 of 21 (76.2%) cases with a mass in the adrenal gland and in 2 of 4 cases with a mass in the kidney. In contrast, CT diagnosis was correct in 2 of 9 (22.2%) cases with a mass in the liver, in 4 of 18 (22.2%) cases with a mass in the adrenal gland and none in a case with a mass in the kidney. In 4 cases with a mass in the spleen, neither US nor CT diagnosis was correct. CONCLUSION: Because organs in the upper abdomen are closely located with each other, correct imaging localization of big mass in this region is not without difficulty. In this series, accuracy of diagnosis with US and CT is comparable, but for localizing tumor in the adrenal gland, US imaging seems superior. US and CT are both incapable of accurately diagnosing large mass in the spleen. PMID- 11776581 TI - [Surgical treatment of gastric cancer in stage T1/T2: an reevaluation of the clinical significance of early gastric cancer]. AB - OBJECTIVE: To evaluate the clinical significance of early gastric cancer by means of an analysis of the results of surgical treatment of gastric cancer in stage T1/T2. METHODS: A retrospective review and survival analysis of 132 patients with stage T1/T2 stomach cancer treated from 1983 through 1993 was performed. RESULTS: The average tumor size, lymph node involvement, postoperative recurrence and survival rate were significantly different between gastric cancer in stage T1 and T2. It was true of both groups of patients that the survival rate of patients with and without lymph node involvement was significantly different. However, the survival rate of patients in stage T2 but without lymph node involvement was not significantly different as compared to that of patients in stage T1. CONCLUSION: For stage T1 stomach cancer, because of possible lymph node involvemnt, local mucosal excision of tumor is not recommended. For stage T2 stomach cancer without lymph node metastasis, it can be regarded as cancer still in its early stage when postoperative adjunct therapy is to be given. PMID- 11776580 TI - [Clinical study of anastrozole in the treatment of postmenopausal women with advanced breast cancer]. AB - OBJECTIVE: To study the effect and adverse reactions of anastrozole in the treatment of postmenopausal women with advanced breast cancer. METHODS: A multicenter, open, non-randomized and crossover clinical trial on the effect of anastrozole was conducted. Sixty-one postmenopausal women with advanced breast cancer were treated by oral anastrozole, 1 mg once every day. Each patient received 4-6 weeks of treatment. Plasma estradiol concentrations were determined 2 weeks before treatment and within 3 days after treatment discontinued. Effect and adverse reaction were evaluated. RESULTS: The response rate in 60 evaluable cases treated with anastrozole was 21.7% (CR = 0, PR = 13, MR = 2). The effect was correlated with postmenopausal time, previous endocrine therapy and ER status. Plasma level of estradiol was suppressed by 58.3%. The main adverse reactions, including nausea, fatigue, facial flush, were generally tolerable. CONCLUSION: As an aromatase inhibitor capable of decreasing plasma estradiol level, anastrozole is therapeutically effective for advanced breast cancer in postmenopausal women. Side effects are mild and tolerable. PMID- 11776582 TI - [Diagnosis and treatment of early gastric cancer: an experience from 61 cases]. AB - OBJECTIVE: To review the clinical signs of diagnostic significance and treatment of early gastric cancer. METHODS: Sixty-one gastric cancer patients were collected for this study. They were surgically treated and pathologically confirmed to be in the early stage of disease. The x-ray and gastroscopic findings of these patients were reviewed. RESULTS: Double-contrast barium meal examination was performed in 46 cases and 27 of them were diagnosed as gastric cancer with a detection rate of 58.7%. Superficial type of tumor was easily misdiagnosed as superficial gastritis and concave type of tumor misdiagnosed as benign gastric ulcer under x-ray imaging. All the patients were gastroscopically examined. With examiner's naked eyes, diagnosis of cancer was made in 27 cases (44.3%). Visual diagnosis was difficult when the tumor was small. Attention should be focused on the gastric incisura angularis, antrum and lesser curvature to perform site-directed biopsy. Final diagnosis depended on the pathological diagnosis of the biopsied materials. Pathologic diagnosis would be correct provided the biopsy material was taken from the proper site. It was correct in 58 of the 61 cases (95.1). Surgical treatment consisted of radical gastrectomy and D2 lymph node dissection. All but 2 were tumor free after surgical treatment. Prognosis was good in this series of early gastric cancer patients, 38 of them were alive over 5 years and 12 patients survived over 10 years. CONCLUSION: Careful x-ray and gastroscopic examinations of patients with epigastric symptoms are indicated not to miss any early case of gastric cancer. PMID- 11776583 TI - [Intervention treatment with percutaneous trans-arterial implantation of port catheter system for advanced cancer patients]. AB - OBJECTIVE: To examine the feasibility, clinical efficacy and complications of percutaneous trans-arterial implantation of port-catheter system (PCS) for intervention treatment of advanced malignant tumors. METHODS: Fifty-three cases with advanced malignant tumors were treated by infusion of chemotherapeutic drugs and/or chemo-embolization through PCS. Patients received one course of treatment every 4-6 weeks. RESULTS: In this series of treated patients, the survival period was 5-18 months with a mean survival time of 13.5 months. The overall response rate (CR + PR) was 62.3%. Detachment of the catheter tip occurred in 2 cases. Disruption of wound after removal of stitches occurred in one case and skin necrosis at the port occurred in another. CONCLUSION: Long-term intervention treatment with PCS is simple and safe. It is a treatment of choice for patients with advanced malignancy. PMID- 11776584 TI - [Cisplatin plus 5-fluorouracil combination therapy in the treatment of advanced esophageal cancer: a report of 156 cases]. AB - OBJECTIVE: To evaluate the results of combination chemotherapy with cisplatin (DDP) plus 5-fluorouracil(5-FU) in the treatment of advanced esophageal cancer. METHODS: From 1988 through 1997, 156 patients with advanced esophageal cancer were enrolled in this study. The median age of the patients was 60. Squamous-cell cancer was the most common type of malignancy. All but 16 patients received no previous chemotherapy. RESULTS: Complete response was observed in 26 patients and partial response in 71 patients, with an overall response rate of 62.2%. The response appeared to correlate with dose intensity, as 65.7% response rate was achieved with a dose of DDP 75-100 mg/m2 versus 43.7% response rate with DDP 50 70 mg/m2. The median response duration was 4.5 months and the median survival period was 8.2 months. Nausea/vomiting, neutropenia and phlebitis were the main adverse reactions in all treated cases. CONCLUSION: A high response rate was obtained in advanced esophageal cancer treated by DDP plus 5-FU with tolerable toxicity. PMID- 11776585 TI - [Retinoic acid enhances chemosensitivity of medulloblastoma cells in vitro and its potential mechanism]. AB - OBJECTIVE: To elucidate the chemosensitivity of retinoic acid (RA)-differentiated medulloblastoma Med-3 cells to conventional anti-cancer drug and to determine the potential genetic factor(s) mediating this sensitivity. METHODS: Ten mumol/L RA, 5 micrograms/ml cisplatin (DDP) and their combination with one half concentration of each were used respectively to treat human medulloblastoma cell line Med-3 in vitro. Cell proliferation, morphology and death pattern as well as Fas/FasL expressions were analyzed by multiple approaches. RESULTS: Both soluble and membrane FasL could be detected in the treated and untreated Med-3. Fas was positive in the cytoplasm of Med-3 cells and the cells could produce soluble Fas. DDP had no obvious effect on Fas expression. RA up-regulated Fas expression and translocalization from cytoplasm to cell membrane of the treated cells. Neither RA nor DDP could trigger apoptosis but in combination could effectively induce apoptosis. CONCLUSION: RA could enhance the apoptotic susceptibility of Med-3 cells to DDP presumably through modulating the Fas expression pattern. Combined RA/DDP regimen would have potential clinical value in the management of medulloblastomas. PMID- 11776586 TI - [The effect of antisense hsp90 beta on the malignant phenotype and sensitivity of HeLa cells to chemotherapeutic drugs]. AB - OBJECTIVE: To study the effects of hsp90 beta on tumorigenesis and sensitivity of HeLa cells to chemotherapeutic drugs. METHODS: A recombinant plasmid expressing either sense or antisense hsp90 beta RNA, and a vector pLXSN were transfected into HeLa cell line by lipofectin method. The transfected cells were screened by G418. The growth rates of the transfected HeLa cells and their sensitivity to adriamycin(ADM) and cisplatin (CDDP) were examined by cell count and MTT uptake. Colony formation in soft agar was used to embody the malignant phenotype in vitro. RESULTS: There was little difference between HeLa cells transfected with sense RNA plasmids and pLXSN vector. The growth rate of HeLa cells transfected with antisense RNA declined, and their ability to form colony in soft agar was decreased. The sensitity of the antisense hsp90 beta transfected HeLa cells to ADM and CDDP increased 2.1-5.8 fold; the LD50 decreased to 1/2-1/5 that of the wild-type HeLa cells. CONCLUSION: Hsp90 beta is involved in the maintenance of malignant phenotype and drug resistance in HeLa cells. PMID- 11776587 TI - [Detecting Epstein-Barr virus in nasopharyngeal carcinoma tissue using in situ polymerase chain reaction]. AB - OBJECTIVE: To develop a sensitive non-isotopic method for in situ detection of Epstein-Barr virus (EBV) in paraffin-embedded section of nasopharyngeal carcinoma (NPC) tissue. METHODS: The EBV BamHI-W fragment labeled with digoxigenin as probe was used to perform in situ hybridization and PCR in situ hybridization (in situ PCR). RESULTS: The method of in situ PCR for the detection of EBV in NPC tissue was proved to be much more sensitive than in situ hybridization. CONCLUSION: Hybridization in situ of PCR product is useful to detect EBV in NPC tissues. PMID- 11776588 TI - [Cloning and antitumor activity of angiogenesis inhibitor HIAF-1]. AB - OBJECTIVE: A new angiogenesis inhibitor HIAF-1 (human inhibitor angiogenesis factor-1) was cloned, expressed in E. coli and its antitumor activity was studied. METHODS: HIAF-1 was amplified by RT-PCR from human fetal liver tissue, then cloned into pET30a(+) vector and expressed in E. coli BL21:DE3 after sequencing. In vitro endothelial proliferation inhibiting activity of HIAF-1 was examined by MTT method. In vivo antitumor activity was studied in a murine model of IVTA2MA-891. RESULTS: HIAF-1 was first cloned from human fetal liver tissue. Sequence analysis of the inhibitor revealed identity to a c-terminal fragment of human collagen XVIII. HIAF-1 was effectively expressed in E. coli with a yield of 88 mg/L. Recombinant HIAF-1 protein could inhibit endothelial cell proliferation in vitro with an IC50 value of 7.5 micrograms/ml. In vivo studies showed that HIAF-1 inhibited growth rate of the primary tumor by 46.6% and metastasis by 68.9%. CONCLUSION: The cloned and the bio-engineering product of HIAF-1 is an angiogenesis inhibitor, capable of inhibiting tumor growth and metastasis. PMID- 11776589 TI - [hCG-PLZF-RARA transgenic mice develop leukemia resembling human chronic myeloid leukemia]. AB - OBJECTIVE: In order to investigate the leukemogenic potential of PLZF-RARA fusion protein in vivo, hCG-PLZF-RARA transgenic mice were generated, in which PIZF-RARA fusion gene was driven by hCG promoter to express in myeloid cells of mice. METHODS: Molecular cloning technology was used to construct hCG-PLZF-RARA gene. The genotype and phenotype of the hCG-PLZF-RARA transgenic mice were analyzed by PCR, RT-PCR, immunofluorescence, morphology of bone marrow (BM) cells, pathology and retinoic acid differentiation assays. RESULTS: Six hCG-PLZF-RARA transgenic mice developed leukemia resembling human chronic myeloid leukemia. TF(tissue factor) was not expressed in BM cells of normal mice nor in mice without the expressed transgene, but it was expressed in mice expessing the transgene. CONCLUSION: PLZF-RARA fusion protein plays a crucial role in leukemogenesis. TF is up-regulated by PLZF-RARA fusion gene. PMID- 11776590 TI - [Expression and prognostic significance of multidrug resistance associated protein (MRP) gene in non-small cell lung cancer by in situ hybridization]. AB - OBJECTIVE: To study the effect of MRP gene overexpression on prognosis of patients with non-small cell lung cancer (NSCLC). METHODS: Paraffin-embedded tissues from 47 cases of NSCLC who had undergone radical tumor resection were examined for expression of MRP gene mRNA by in situ hybridization using labelled digoxigenin probes combined with immunohistochemistry. All the patients were retrospectively followed-up. RESULTS: All of the 47 lung cancer specimens were found to have overexpression of MRP mRNA. It was significantly correlated with patients' survival period, response to chemotherapy, recurrence and mestastases after surgery, but was not correlated with histology, tumor size, node status, TNM stage, degree of differentiation, age and sex. CONCLUSION: Overexpression of MRP gene is a marker of prognostic significance in patients with NSCLC. PMID- 11776591 TI - [Prognostic value of serum CA125 level in patients with advanced non-small cell lung cancer]. AB - OBJECTIVE: To judge the prognostic value of serum CA125 level in patients with advanced non-small cell lung cancer. METHODS: Sixty-six untreated patients with advanced non-small cell lung cancer (NSCLC) confirmed histologically were studied. They received two to four cycles of chemotherapy, some of them combined with radiotherapy. All these patients were assayed for serum CA125 before treatment. The cut-off value of serum CA125 level was 35 U/ml. RESULTS: Increased serum CA125 levels were observed in 24 out of 66 patients (36.4%). Patients with increased serum CA125 levels had an average survival rate of 12.5% at 1 year and 0 at 2 years, whereas that of patients with normal serum CA125 levels was of 57.1% at 1 years, 14.3% at 2 years and 7.1% at 3 years. Cox proportion hazard multivariate analysis showed that the prognosis of patients was related to serum CA125 levels (P = 0.000) and effects of treatment (P = 0.046). CONCLUSION: CA125 can be used as an independent prognostic parameter in advanced NSCLC. PMID- 11776592 TI - [The expression and clinical significance of keratin 19, 20 mRNA in different tumor cell lines and tumor tissues]. AB - OBJECTIVE: To study the expression of keratin 19, 20 (K19, K20) in different tumor cell lines and tumor tissues and its clinical implication. METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed to examine the specific expression of K19 and K20 mRNA in eleven tumor cell lines and 33 corresponding tumor tissue specimens. RESULTS: The expression of K19 mRNA was detected in 4 kinds of tumor cell lines and all tumor tissues examined, but the magnitude of expression differed, with a difference ranging from 1.7 to 10 folds for the same type of cancer. In some patients, the level of expression was as low as 12% of the positive control. K20 mRNA expression was negative for lung and esophageal tumor cell lines and the corresponding carcinoma specimens. In one of 6 bladder cancer specimens and in 4 of 5 colorectal cancer tissues, K20 expression was positive, at a level of 41%-77% of the positive control. There was no expression of K20 in bladder tumor cell line EJ1 and colorectal tumor cell line SW480. CONCLUSION: These results demonstrate that K19 and K20 may be used as a valuable marker for detecting circulating cancer cells, but the low level of expression in some cases of carcinoma would probably result in false negative results. PMID- 11776593 TI - [Molecular cytogenetic study of bladder transitional cell carcinoma by FISH]. AB - OBJECTIVE: To study the molecular cytogenetic alterations of transitional cell carcinoma of the urinary bladder with exfoliated cells. METHODS: Fluorescence in situ hybridization (FISH) was performed using centromeric probes of chromosome 7, 9, 11 and 17 to examine chromosome aberration of exfoliated cells in 34 urine samples and 30 bladder washings from patients with transitional cell urinary bladder carcinoma. RESULTS: (1) The frequency of numerical aberration of chromosome 7, 9, 11, 17 was 23.5%, 38.2%, 14.7% and 11.8% in urine and 30.0%, 50.0%, 26.7% and 16.7% in bladder washing, respectively. Loss of chromosome 9 was the most common finding, but it was not correlated with pathological grade of cancer and stage of the disease. Abnormality of chromosome 7 was however associated with the clinical stage. (2) The positive rate of examination by cytology and FISH was 29.4% and 55.9% in urine, 27.6% and 73.7% in bladder washing, respectively. When the results of cytology and FISH were combined, the positive rate increased to 67.6% and 80.0% for urine and bladder washing, respectively. CONCLUSION: A number of chromosome aberrations is detected in transitional cell carcinoma of the urinary bladder by FISH technique which provides a basis for further understanding of its molecular pathogenesis and clinical applications. PMID- 11776594 TI - [Expression of caspase3 gene does not correlate with tumor cell apoptosis in primary hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the relationship between caspase3 expression and apoptosis in hepatocellular carcinoma (HCC). METHODS: In situ hybridization was employed to determine caspase3 expression, and in situ end-labeling was used to detect apoptotic cells in HCC. RESULTS: Twenty one of 39 (53.8%) cases of HCC were found to express caspase3 transcripts, while 46.2% of HCC failed to express it. Adjacent non-cancerous liver tissues showed more caspase3 positiveity (87.5%, 7/8) as compared with HCC (P < 0.05). The expression of caspase3 was correlated with HCC differentiation, as 72.2% (13/18) of moderately to well differentiated HCC showed positive caspase3 transcripts, while only 38.1% of poorly differentiated HCC was caspase3 positive (P < 0.05). No relationship was found between caspase3 and tumor size or grade or metastasis, although 62.5% (5/8) of HCC with metastasis was caspase3 positive but it did not differ significantly from that without metastasis (P > 0.05). Expression of caspase3 alone did not affect the apoptosis index (AI) of HCC. AI was 7.1@1000 in caspase3-positive tumors (n = 21), as compared to 6.6@1000 (n = 18) in caspase3-negative cases (P > 0.05). CONCLUSION: Although loss of caspase3 expression may contribute to hepato carcinogenesis, its expression may not be related to cell apoptosis in HCC. PMID- 11776596 TI - [The value of CEA mRNA, CEA protein and cytology of peritoneal washings in the prediction of metastasis of gastric cancer]. AB - OBJECTIVE: To ascertain the usefulness of CEA determination and cytology of peritoneal washings in the prediction of metastasis of gastric cancer to the peritoneum. METHODS: CEA was detected at mRNA level by RT-PCR and at protein level by radioimmunoassay (RIA). Cytologic examination was done by conventional method. Peritoneal washings were collected during operation from 43 patients with gastric carcinoma and 10 with benign lesions. RESULTS: The positive rate of RT PCR was 56.3% and that of RIA was 38.1%. Both were more sensitive than that of cytologic examination (33.1%) of free cancer cells in the peritoneal washings. The level of CEA mRNA expression increased with the depth of invasion and stage of the disease. It also varied significantly in tumors different in the gross type and serosal involvement. CONCLUSION: To detect CEA in peritoneal washings by RT-PCR and RIA, and to examine them for tumor cells by cytotogic method are useful to predict subclinical metastasis to the peritoneam in patients with gastric carcinoma, but RT-PCR is most sensitive. PMID- 11776595 TI - [Intervention treatment of hepatocellular carcinoma with 125I-lipiodol plus chemotherapeutic drugs and self body hairs: a report of 56 cases]. AB - OBJECTIVE: To study the therapeutic effects on primary hepatic cancer of intervention treatment with a preparation consisting of 125I-iodinated lipiodol ultrafluid (LUF) plus self body hairs and cell-cycle nonspecific chemotherapeutic agents. METHODS: The treatment was given to 56 patients with primary hepatic cancer. CT, US, DSA, serum AFP determination, and urine radioactivity were carried out before and after treatment. RESULTS: The preparation was found to be held up in the end arteries supplying the tumor for a considerable length of time without passing through blood capillaries into the general circulation. It helped keep the chemotherapeutic drugs and internal radiation staying at the tumor site. The side effects of this treatment were tolerable. No rejection reaction was observed. In thirty six of the 56 patients (64.3%), the tumor reduced by 50%-70% in diameter, and in the remaining 20 patients(35.7%) the reduction in tumor diameter was less than 50% or not at all. The clinical manifestations, liver functions and serum AFP level improved in all cases. The survival rate in 6, 12, 24 and 36 months was 100%, 82.1%, 63.1% and 55.6%, respectively. CONCLUSION: The new intervention treatment for primary liver cancer herein described is easy to perform and can significantly improve survival and quality of life. PMID- 11776597 TI - [Minimal residual disease in bone marrow in patients with Ewing's sarcoma detected by RT-PCR amplification of EWS-FLI-1 fusion gene transcript]. AB - OBJECTIVE: To set up a system for sensitively detecting minimal Ewing's sarcoma cells in bone marrow. METHODS: Ewing's sarcoma cell line T1 cells were serially diluted with normal bone marrow cells so that the concentration of tumor cells was 10(-3), 10(-4), 10(-5), 10(-6), 10(-7), and 0, respectively. Total RNA was isolated from these samples and cDNA was synthesized. EWS-FLI-1, a fusion gene formed due to chromosome translocation, was amplified with PCR. Bone marrow samples from five patients with Ewing's sarcoma patients with tumor metastasis were examined for EWS-FLI-1 transcript. RESULTS: T1 cells could be detected when one was present in 10(6) normal bone marrow cells. Thus the sensitivity of detection was 10(-6). A 434 bp EWS-FLI-1 transcript was detected in five Ewing's sarcoma patients examined at the time of diagnosis. After complete remission, EWS FLI-1 was still positive on RT-PCR in 3 patients, although BM pathological examination was negative in all cases. CONCLUSION: RT-PCR for EWS-FLI-1 is sensitive enough to detect minimal residual Ewing's sarcoma cells in the bone marrow. It can identify residual tumor cells in pathologically negative bone marrow specimens. PMID- 11776598 TI - [Susceptibility to lung cancer in Chinese is associated with genetic polymorphism in cytochrome P4502E1]. AB - OBJECTIVE: To investigate the genetic polymorphism of cytochrome P4502E1 (CYP2E1) as a susceptibility factor for lung cancer in Chinese population. METHODS: The genotype frequencies of RsaI restriction fragment length polymorphisms were analyzed in 92 lung cancer cases and 137 frequency-matched normal controls. RESULTS: The CYP2E1 c1/c1 genotype was found in 72.8% of lung cancer cases, which was significantly higher (P < 0.01) than that in controls (54.7%). By multivariate analysis, this genotype was found to be associated with a 2.5-fold increased risk of lung cancer (adjusted OR 2.5, 95% CI 1.8-3.8). Stratified analysis suggested an interaction between CYP2E1 c1/c1 genotype and cigarette smoking. The odds ratio (OR) for the CYP2E1 c1/c1 genotype, cigarette smoking and both factors combined was 3.9 (95% CI 1.1-15.2), 4.1 (95% CI 1.1-15.9) and 7.9 (95% CI 2.4-29.4), respectively. The interaction between CYP2E1 c1/c1 genotype and pack-years of cigarette smoking followed the same pattern, with a markedly increased risk in the heaviest smokers. CONCLUSION: The CYP2E1 c1/c1 genotype is a susceptibility factor for development of lung cancer in Chinese and there is an apparent gene-environment interaction between the susceptible genotype and cigarette smoking. PMID- 11776599 TI - [The study of nitric oxide synthase in ovary tumor]. AB - OBJECTIVE: To study the activity of nitric oxide synthase (NOS) in ovarian tumors. METHODS: Spectrophotometry was used to examine NOS activity and NADPH diaphorase histochemistry to identify its localization. RESULTS: The activity of NOS was significantly higher in malignant than in normal ovarian tissue and benign ovarian tumors (P < 0.01). There was negative correlation between NOS activity and tumor cell differentiation. NOS reaction product was mainly located in cancer cells, and was negative in the interstitial tissue. Furthermore, NOS was mostly located in membrane and cytoplasm of the cancer cell. CONCLUSION: Increase in nitric oxide synthase activity might be related to the growth and malignant behavior of ovarian cancer. PMID- 11776600 TI - [Cytologic and histopathologic examinations of fine-needle aspirates of pancreatic mass]. AB - OBJECTIVE: To evaluate the usefulness in diagnosis of pancreatic mass by histopathologic and cytologic examinations of fine-needle aspirates obtained under ultrasonic guidance. METHODS: In 83 patients with pancreatic mass, percutaneous fine-needle aspiration was performed under ultrasound guidance. The fluid aspirates were examined cytologically and tissue fragments examined histopathologically. The findings were compared. RESULTS: The rate of accuracy, sensitivity, and specificity of cytologic examination was 98.8%, 98.3% and 100% respectively, and that of histopathologic diagnosis was 95.1%, 93.2% and 100%, respectively. There was no false positive. CONCLUSION: Both histopathologic and cytologic examinations of fine-needle aspirates of pancreatic mass are sensitive and accurate enough for the diagnosis of pancreatic diseases. They can be used with complementarity. PMID- 11776601 TI - [Effect of tamoxifen on apoptosis and drug resistance of breast cancer cells in vitro]. AB - OBJECTIVE: To study the effect of estradiol (E2) and tamoxifen (TAM) on the apoptosis regulatory genes (bax, bcl-2) and mdr-1 in MCF-7 cells. METHODS: Immunohistochemistry, in situ hybridization were used to observe the changes in bax, bcl-2 and mdr-1 genes after treatment with E2 and TAM. RESULTS: E2 had ability to increase the expression of bcl-2 and mdr-1 but TAM decrease the expression of both. Synthetic bax oligodeoxynucleotide (ODN) was used as probe to perform in situ hybridization. It was shown that bax mRNA in MCF-7 cells was down regulated by E2 and up-regulated by TAM. Significant correlation between bcl-2 and mdr-1 was observed after TAM treatment of MCF-7 cells (P < 0.05). CONCLUSION: TAM regulates cell apoptosis and inhibits development of drug-resistance of MCF-7 breast cancer. PMID- 11776602 TI - [The value of STIR pulse sequence MR imaging in patients with pulmonary carcinoma]. AB - OBJECTIVE: To evaluate the value of short TI inversion-recovery (STIR) MR imaging technique in diagnosing pulmonary carcinoma. METHODS: One hundred and eight patients with pathologically confirmed pulmonary carcinoma were examined by STIR pulse sequence and the results were compared with these by SE pulse sequence. RESULTS: STIR MR imaging was superior to conventional SE pulse sequences in significantly increasing the detection rate of lesions, improving images along the edge of the lesion, tumor invasion to adjacent structures, and demonstrating lymph node enlargement. CONCLUSION: STIR, with its sensitivity, is particularly useful to reveal metastatic lymph nodes and invasion to the pleura and chest wall. PMID- 11776603 TI - [Combined hepatic artery chemoembolization and portal vein chemotherapy after radical resection of hepatocellular carcinoma to prevent recurrence]. AB - OBJECTIVE: To study the value of combined hepatic artery chemoembolization (HACE) and portal vein chemotherapy (PVC) after radical resection of hepatocellular carcinoma (HCC) to prevent recurrence. METHODS: From August 1991 to July 1995, 81 HCC patients were undergone radical tumor resection. After operation, combined treatment with HACE and PVC was given in group I (28 cases), HACE alone in group II (30 cases), nothing in group III (28 cases). All patients were followed up over 3 years. RESULTS: Recurrence rate at one year after surgery was significantly lower in group I and II than in group III; at two years, it was lower in group I than in group II and III. Survival rate at one year was notably higher in group I and II than in group III; at 2 years, it was higher in group I than in group II and III. Recurrence rate and survival rate were similar in group I and group II at 3 and 5 years after surgery. Tumor larger than 5 cm, no capsule, multiple foci, AFP > 400 micrograms/L were high risk factors of postoperative recurrence. CONCLUSION: After radical resection of HCC, combined use of HACE and PVC is superior to HACE alone to reduce recurrence rate and to increase survival rate within 2 years after operation. Such remarkable difference no more exists at 3 and 5 years following operation. PMID- 11776604 TI - [Breast cancer accompanied by Paget's disease: an anlysis of 34 cases]. AB - OBJECTIVE: To better understand the clinical and pathological features, diagnosis, treatment and prognosis of Paget's disease accompanying breast cancer. METHODS: From 1958 to 1997, 34 such patients were operated and pathologically confirmed. RESULTS: Breast cancer combined with Pagat's disease accounted for 0.9% of the total number of breast cancer patients treated in the same period of time. The mean age of patients was 47.3 years, and the mean duration of symptoms was 23.9 months. The patients received combination treatment with surgery as the major treatment modality. Among patients with nipple change as the first symptom, 26.7% of them had positive axillary nodes. The rate of metastasis was 26.7% as confirmed by surgical pathology. The 5-, 10-, and 20-year survival rate was 93.1%, 78.1% and 67.0%, respectively. Among those with palpable mass as the first symptom, metastasis to the axillary lymph nodes occurred in 52.6% of the cases, and distant metastasis in 42.1% of the cases. The rate of 5-, 10- and 20-year survival rate was 60.5%, 53.8% and 53.8%, respectively. CONCLUSION: Paget's disease, as a special form of breast cancer, may accompany cancer inside of the breast. In patients whose disease is confined to the nipple, their prognosis is better than those accompanied by palpable mass in the breast. PMID- 11776605 TI - [Percutaneous tubing and drainage for the diagnosis and treatment of malignant pericardial effusion]. AB - OBJECTIVE: To insert a tube into pericardial cavity as an emergent measure of diagnosis and treatment in patients with malignant pericardial effusion. METHODS: Pericardial puncture was followed by insertion of drainage tube (diameter = 1.8 mm) through the puncture needle. The effusion collected was examined for cancer cells. After drainage, chemotherapeutic agents were administered. Four hours later, drainage was continued for 2 days (< or = 30 ml pericardial fluid drained in 24 hr) and the tube was removed. RESULTS: In 34 cases with malignant pericardial effusion, tube draining was successful to relieve cardiac temponade within 15-60 minutes. Clots were present in 91.2% of the cases and cancer diagnosis was confirmed in all of them. The cytologic diagnosis of effusion was positive in 61.8%, and the cyto-pathologic typing of clots was 81.0%. The difference was statistically significant. When the results of the 2 examinations were put together, the positive rate increased to 94.1%. CONCLUSION: Tube drainage of malignant pericardial effusion is useful in diagnosis and emergency treatment. PMID- 11776607 TI - [Diagnosis and treatment of colorectal non-epithelial malignancies]. AB - OBJECTIVE: To summarize the experience in the diagnosis and treatment of colorectal malignancies of non-epithelial origin. METHODS: Seventy five cases of colorectal non-epithelial malignancy who had undergone treatment in our hospital from 1975 to 1996 were retrospectively analysed with their clinicopathologic characteristics, treatment and prognosis. RESULTS: Patients usually had no specific clinical manifectation, such as bloody purulent stool or mucous stool. No apparent mucosa damage other than changes due to pressure from without was found on x-ray and colonoscopic examinations. Diagnosis depended on pathology and clinical manifestations. Metastasis occurred mainly by hematogenous spread and local invasion. In this series, 21 cases (6 liomyosarcomas; 15 lymphosarcoma) had local recurrence. The principle treatment was operation, which was performed two or several times in patients with local recurrences. Except lymphosarcoma, the disease was not sensitive to chemotherapy or radiotherapy. The survival rate was significantly lower than that of colorectal cancers. CONCLUSION: The disease is apt to be misdiagnosed or missed because it lacks specific symptoms. Local recurrence and hematogenous metastasis are common. PMID- 11776606 TI - [Nasea injection in the prophylaxis of gastrointestinal reaction induced by chemotherapeutic agents]. AB - OBJECTIVE: To evaluate the efficacy and side effects of nasea injection for the prophylaxis of gastrointestinal reactions induced by chemotherapeutic agents, and compare them with those of kytril. METHODS: A multicenter, open, randomized self crossover control trial was carried out. All the eligible patients were randomized into AB or BA group. The patients in AB group were treated by nasea in the first cycle and kytril in the second cycle, those in BA group were treated with the drugs in the reverse order. RESULTS: In patients enrolled in this study, 98 patients were evaluable for response, including 61 patients in DDP-arm and 37 in ADM-arm. Nasea was as effective as kytril in the control of anorexia, nausea and vomiting in the 0-6 hour period after chemotherapy. Nasea was significantly superior to kytril in the complete control of anorexia (38.8% vs 25.5%, P < 0.05) in the 0-24 hour period. The overall control rate of nausea by nasea in the 0-12, 0-18, and 0-24 hour period was 73.6%, 71.4%, 67.3%, respectively, which was significantly higher than that by kytril (65.3%, 61.2%, 48%). Nevertheless, in the control of vomiting in the 0-24 hour period, no statistical difference between the two drugs was observed. Nasea and kytril were equally effective in the control of anorexia, nausea and vomiting induced by DDP and ADM. The side effects of nasea were head heaviness, headache, dry mouth and constipation, etc. All of these were mild and comparable with kytril in their frequencies. CONCLUSION: Nasea can effectively prevent the gastrointestinal reaction induced by chemotherapeutic agents. The side effects of nasea are similar to those of kytril but its effect to alleviate gastrointestinal reactions is of longer duration. PMID- 11776608 TI - [The use of interposed colon for endothoracic anastomosis in esophageal surgery]. AB - OBJECTIVE: To study the use of interposed colon for endothoracic anastomosis in esophageal surgery. METHODS: From May 1991 to December 1993, 28 cases were selected with carcinoma of the middle and/or lower segment of esophagus. After tumor resection, a segment of transverse colon with peduncle was anastomosed in its peristaltic direction to the two ends of the severed esophagus. The vagus nerve innervating esophagus and stomach was intact, the anastomical position of the esophagus-cardia hiatus and the stomach were preserved. RESULTS: No anastomosis leakage, reflux esophagitis or the symptoms caused by the endothoracic stomach occured in this group. The digestive function of the patients remained good. The 1-, 3-, 5-year survical rate was 96.6%, 92.8% and 71.4%, respectively. CONCLUSION: The interposed colon for endothoracic anastomosis is a comparatively ideal method for the reconstruction of esophagus following resection of cancer of mid and lower thind of the esophagus. PMID- 11776609 TI - [Numerical alteration of chromosome 8 in pleural effusions]. AB - OBJECTIVE: To study the numerical alteration of chromosome 8 and its application for detecting cancer cells in the pleural effusions. METHODS: In situ hybridization with chromosome 8 centromere probe was carried out in 52 patients with pleural effusions. RESULTS: In 31 lung cancer patients examined, hyperdiploid chromosome 8 was found in the effusions. The same hyperdiploid of the chromosome was also noted in 4 cases of effusion from adenocarcinoma of breast, mesothelioma and lymphoma. In 15 pleural effusions which were reportedly negative in previous cytological diagnosis, hyperdiploid chromosome 8 was found in 3 cases, and diploid chromosome 8 in another 12 cases by in situ hybridization. After reexemination of the samples from the 3 patients with hyperdiploid chromosome 8, adenocarcinoma cells were found in 2 cases, and the third one was a patient being treated with radiotherapy. Hyperdiploid chromosome 8 also existed in the pleural effusions from 2 cases suspicious of adenocarcinoma. CONCLUSION: Hyperdiploid chromosome 8 may be a useful marker to ascertain the malignant nature of pleural effusion. PMID- 11776610 TI - [Combination chemotherapy of uterine sarcomas]. AB - OBJECTIVE: To study the results of combination chemotherapy of uterine sarcoma after operation and recurrent tumor. METHODS: One hundred seventy-four cases of three major pathological subtypes of uterine sarcomas were treated in the Cancer Hospital from 1960 to 1996. Clinical data were analyzed of 51 cases of uterine sarcomas treated with postoperative adjuvant chemotherapy and 38 cases with recurrent tumors received 98 courses of chemotherapy. They were divided into 4 groups according to the adjuvant chemotherapy regimen: single drug, VAC, VAD, and other regimens. Chemotherapy regimens for recurrent tumors were VAD, PA/PAC, and other combination regimens including etoposide, ifosfamide, cisplatin, adriamycin. RESULTS: The 5-year survival rate of stage I-II uterine sarcoma patients was 54.9% receiving adjuvant chemotherapy. It was 72.7% in VAD group which was significantly higher than that in other regimen groups. The survival rate was related to the number of chemotherapy course. The chemo-sensitivity of various pathological types of recurrent uterine sarcomas was not different. CONCLUSION: The 5-year survival rate does not improve in patients with stage I-II uterine sarcomas given postoperative chemotherapy. VAD is among the best regimens and at least 3 courses should be performed. The results of new treatment regimens such as EPA, IA, etc., must await further clinical observation. PMID- 11776612 TI - [Study of APC, Rb, c-met gene copy numbers of human gastric mucosa epithelial cell line GES-1]. AB - OBJECTIVE: To study the copy number of oncogene/tumor suppressor genes in GES-1 cell line to identify its characteristics. METHODS: Bio-14-dATP was incorporated into APC, Rb, c-met gene cloned in plasmid by nick translation. Fluorescence in situ hybridization (FISH) of interphase nuclei of GES-1 cells was performed. RESULTS: Two copies of APC were shown in 48% interphase nuclei and 3 copies in 22%; 71% and 80% cells had normal copies of Rb and c-met genes in their nuclei, respectively. CONCLUSION: GES-1 cell line is a relatively normal gastric mucosa epithelial cell line and can be used as a human in vitro model system for the study of carcinogenesis. PMID- 11776611 TI - [Preliminary study on the antitumor immuno-protective mechanism of beta-elemene]. AB - OBJECTIVE: To study the antitumor effects and their molecular mechanism of beta elemene, which is one of the effective monomers of Oleum Curcuma aromatica, a Chinese anticancer medicament. METHODS: The expression of membrane protein HSP70 on H22 cells treated with beta-elemene or mitomycin C(MMC) was analysed by immunofluorescence and flow cytometric techniques and the antitumor effects of the treated H22 cells was examined in C57BL/6 mice. RESULTS: The expression rate or intensity of membrane protein HSP70 of H22 cells treated with beta-elemene, and those treated with MMC was both significantly higher than that of the untreated H22 cells (P < 0.001). Increase in HSP70 expression was most marked when H22 cells were treated with beta-elemene and MMC in combination, with an expression rate of 95.1%. Heat shock treatment of the H22 cells combined with other stress-inducing factors could further increase the HSP70 expression intensity. Specific antitumor immunity could be elicited in C57BL/6 mice immunized with beta-elemene-treated H22 cells, and the effect could be partially blocked by anti-HSP70 mAb. In mice immunized with beta-elemene-treated H22 cells, tumor developed in 3 of 11 mice, while in the immunized mice given anti-HSP70 mAb, 5 out of 10 mice developed tumor, and all of the control mice developed tumor. The average tumor weight (g) on day 28 after challenge with untreated H22 cells was 0.17 +/- 0.33, 0.66 +/- 0.77 and 1.11 +/- 0.58 in the three groups of mice, respectively. CONCLUSION: beta-elemene increases tumor cell immunogenicity by inducing, at least in part, elevated expression of heat shock protein 70 on tumor cell surface. PMID- 11776613 TI - [Construction of anti-human VEGF165 chimeric antibodies and expression in eukaryotic cells]. AB - OBJECTIVE: To express chimeric anti-VEGF165 antibody genes in eukaryotic cells. METHODS: The variable region genes of light and heavy chains from mouse anti human VEGF165 monoclonal antibody VmD11 were cloned into eukaryotic expression vectors and transfected into dihydrofolate reductase-deficient Chinese hamster ovary(CHO-dhfr-) cells to express chimeric antibody. The antibody expressed was examined for the presence of human constant regions and specificity against human VEGF165. RESULTS: The chimeric antibody with human constant regions and specificity against human VEGF was detected in the culture supernatant of transfected CHO cells by ELISA and Western blot. The chimeric antibody gene was also detected at mRNA level by RT-PCR. CONCLUSION: The mouse anti-human VEGF165 monoclonal antibody is successfully humanized and expressed in eukaryotic cells. PMID- 11776615 TI - [Detailed deletion mapping of chromosome 9p21-22 in nasopharyngeal carcinoma]. AB - OBJECTIVE: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma(NPC) and provide evidence for discovering new tumor suppressor genes. METHODS: Loss of heterozygosity (LOH) on chromosome 9p21-22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. RESULTS: Of the 25 cases, 17(68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161(35.0%), D9S1678(31.6%), D9S263 (33.3%) and D9S1853(33.3%). In 6 cases, contiguous stretch of allelic loss was found. CONCLUSION: The minimal common region of deletion might be defined between D9S161 and D9S1853 (approximately 2.7 cM in length) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC. PMID- 11776614 TI - [The inhibitory effect of recombinant fibronectin polypeptide CH50 on the growth of B16 melanoma]. AB - OBJECTIVE: To study the inhibitory effect of CH50, a recombinant polypeptide consisting of 2 binding domains of human fibronectin, on the growth of B16/F1 melanoma in mice. METHODS: Mice inoculated with B16/F1 cells were treated with CH50. The growth inhibitory effect on i.p. inoculated tumor was assessed by the number and size of tumor nodules in the peritoneal cavity, and on s.c. inoculated tumor by tumor size. RESULTS: For s.c. inoculated B16/F1, CH50 injected at the tumor site led to 50% inhibition of tumor growth while injection at a distant site was much less effective. In mice bearing i.p. inoculated tumor, the growth inhibition by CH50 on tumor nodules < 1 mm in diameter was 80% and 50+% on those > 1 mm. Synergistic therapeutic effect was obtained when CH50 used in combination with hydroxycamptothecine (HCPT). CONCLUSION: CH50 is effective in the treatment of B16/F1 melanoma. The effect can be enhanced when used in combination with HCPT. PMID- 11776616 TI - [Expression and reversion of drug resistance- and apoptosis-related genes of a DDP-resistant lung adenocarcinoma cell line A549DDP]. AB - OBJECTIVE: To study the expression of drug resistance- and apoptosis-related genes of A549DDP cells as compared to the parental cell line A549, and its reversion by antisense s-oligodeoxynucleotide (S-ODN) of the differentially expressed genes. METHODS: Sense and antisense S-ODN were transferred into A549DDP cells by lipofectin. Expression of genes related to drug resistance and apoptosis was examined by RT-PCR, immunocytochemistry and flow cytometry. Apoptosis was identified by DNA electrophoresis and TUNEL, and cell growth by MTT uptake. RESULTS: The expression of bcl-2 was positive and that of MRP at mRNA and protein levels was increased in A549DDP cells compared to A549 cells. MDR1, c-myc and TOPO II were similarly expressed in the two cell lines. Both cell lines were negative for c-erbB-2 expression. In A549DDP cells, the expression of bcl-2 and MRP was significantly inhibited by respective antisense S-ODN. Antisense S-ODN could also significantly inhibit proliferation of A549DDP cells, and promote cell apoptosis by reducing its resistance to cisplatin. CONCLUSION: Bcl-2 and MRP genes are responsible for the induced resistance of A549DDP cells to cisplatin. PMID- 11776617 TI - [Antitumor effect of peri-cryosurgical immunotherapy]. AB - OBJECTIVE: To evaluate the anti-tumor effect of combined cryosurgery and immunotherapy in mice. METHODS: C57BL/6 mice bearing B16 melanoma were randomly divided into 3 groups: (1) peri-cryosurgical immunotherapy group, (2) cryosurgery group, (3) immunotherapy group and (4) saline group. RESULTS: The tumor size on day 35 was 0.4 cm3 in group 1, 1.1 in group 2, 1.9 in group 3, and 3.9 in group 4 of mice. The survival period was 71, 62, 53 and 46 days, respectively. None in group 3 and 4 was cured, while 14% of mice in group 2 and 50% in group 1 were tumor tree. In tumor-free mice, no tumor cell in the primary tumor sites was found by light and electron microscopy 3 months later. CONCLUSION: The combined use of cryosurgery and immunotherapy is curative in 50% of mice bearing established B16 melanoma. PMID- 11776618 TI - [Microvessel quantitation and expression of VEGF in colorectal tumors]. AB - OBJECTIVE: To evaluate angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation and VEGF status. METHODS: Thirty two colorectal carcinomas, 5 adenomas and 10 normal mucosa were studied immunohistochemically for microvessels and expression of VEGF. RESULTS: The mean vascular density (MVD) was 11 +/- 4 in normal mucosa, 28 +/- 11 in adenomas, and 50 +/- 22 in carcinomas (normal versus adenomas P > 0.05; normal versus carcinomas P < 0.01; adenomas versus carcinomas P < 0.05). MVD varied with tumor cell differentiation and tumor stage, but the differences were not significant. The expression of VEGF is closely associated with angiogenesis. Both MVD and VEGF expression were associated with prognosis. CONCLUSION: VEGF status and MVD are of prognostic significance in colorectal cancer patients. PMID- 11776619 TI - [Immunohistochemical study of angiogenesis of axillary lymph node metastasis in human breast carcinoma]. AB - OBJECTIVE: To study angiogenesis of axillary lymph node metastases (including micrometastatic foci and metastatic tumors) in breast carcinoma and the relationship between microvessel density (MVD) and metastasis. METHODS: Thirty seven breast cancer tissues and 121 metastatic axillary lymph nodes were collected from breast cancer patients and studied immunohistochemically. MVD was counted by means of microvideo system under 100x magnification. The diameter of each micrometastasis was measured with a micrometer. RESULTS: The mean diameter of 13 micrometastatic foci was 210 +/- 37 microns. No blood vessel formation was found. MVD of the primary tumor and that of metastatic tumor in the axillary lymph node was 93.8 +/- 21.8 and 89.3 +/- 18.4, respectively (P > 0.05). The distribution of microvessels of the metastatic tumor in the lymph node and that of the primary tumor was similar, being higher at the periphery than at the center. CONCLUSION: Micrometastatic foci of breast carcinoma in the axillary lymph node do not have new blood vessel formation. Their further growth, however, depends on neo-angiogenesis. Treatment based on inhibition of angiogenesis may be efficacious in the prevention of micrometastatic foci from developing into metastatic tumor in lymph node. PMID- 11776620 TI - [FHIT gene is abnormal in laryngeal carcinoma]. AB - OBJECTIVE: To determine the role of FHIT gene in laryngeal carcinogenesis. METHODS: Laryngeal cancer cell line Hep-2, HeLa cell line and 80 primary tumors from patients with laryngeal cancer were studied by means of RT-PCR, sequencing and microsatellite analysis. RESULTS: Abnormal transcripts of FHIT gene were found in the two cell lines and 70% (14/20) of primary laryngeal carcinomas. Aberrant laryngeal tumor transcripts often lack more than two exons of FHIT gene. Microsatellite analysis showed that both loss of heterozygosity and microsatellite instability of FHIT gene existed in laryngeal carcinoma and the former was more common. CONCLUSION: FHIT gene participates in the laryngeal carcinogenesis and may be one of the candidate tumor suppressor genes. PMID- 11776621 TI - [Prediction of the outcome of dysplasia of esophageal epithelium by high resolution image analysis]. AB - OBJECTIVE: To predict the outcome of dysplasia of esophageal epithelium by means of high resolution image analysis(HRIA). METHODS: Asymptomatic adults were examined for balloon cytology of the esophagus in 1983 from Heshun Commune of Linxian County. Ninety three cases of severe dysplasia and 122 cases of mild dysplasia of the esophagus were selected for this study. By means of an Axiomat microscope equipped with TV-camera, 100 normal nuclei of well-preserved cells in the intermediate layer of Pap-stained squamous epithelium were randomly examined. RESULTS: Of the 93 cytologically diagnosed severe dysplasia cases, 24, 14 and 7 progressed to carcinoma in 3, 5 and 9 years, respectively. In the other 48 cases, dysplasia remained stable or regressed to normal. The other cases were used as the control. According to chromatin features, correct diagnosis of cases was achieved by HRIA in 75.0%(18/24), 85.7%(12/14) and 85.7%(6/7) of the cases examined, respectively (P < 0.001). Of the 122 cytologically diagnosed mild dysplasia, 16, 13 and 12 cases progressed to carcinoma in 3, 5 and 9 years, respectively. The other 81 cases remained stable or regressed to normal. Correct diagnosis was made by HRIA in 93.8%(15/16), 76.9%(10/13) and 83.3%(10/12) of the cases examined, respectively (P < 0.001). CONCLUSION: Chromatin nuclear features examined by HRIA can predict the outcome of precancerous lesions and discriminate progressor from non-progressor ones. It can be used as surrogate endpoint biomarkers for the evaluation of efficacy of chemoprevention trial. PMID- 11776622 TI - [The role of cytokeratin 13 gene in human nasopharyngeal carcinoma]. AB - OBJECTIVE: To study the significance of cytokeratin 13 (CK13) gene expression and its methylation in human nasopharyngeal carcinoma (NPC). METHODS: The expression of CK13 in 32 cases of NPC and 8 cases of chronic inflammatory diseases of nasopharyngeal epithelia (CIDNE) was studied using Northern blot hybridization. The methylation pattern of CK13 gene was analyzed by Southern blot hybridization using methylation sensitive restriction endonuclease Hpa II and Msp I in NPC cell lines HNE1 and normal human primary cultures of nasopharyngeal epithelial cells. RESULTS: High expression of CK13 gene was found in 8(100%) CIDNE, low-expression of the gene in 12(37.5%) NPC, negative expression in 9(28.1%) and high expression in 11(34.4%). The degree of methylation was increased in NPC cell lines HNE1, compared to that of normal human primary cultures of nasopharyngeal epithelial cells. CONCLUSION: The expression of the CK13 gene in NPC is partly or completely down regulated. It is possibly related to hyper-methylation of CK13 gene. PMID- 11776624 TI - [The value of spiral CT in CT arterial portography and CT hepatic arteriography]. AB - OBJECTIVE: To evaluate the usefulness of spiral CT in CT arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHODS: The CTAP and CTHA manifestations in 50 patients with small hepatocellular carcinoma (< 3 cm in diameter) were analyzed and compared with those in bi-phase enhanced CT. RESULTS: The detection rate of CTAP and CTHA was 92.2% and 90.1%, respectively. They could reveal tumors of 0.2 cm-0.5 cm in diameter. Both CTAP and CTHA gave false positive findings, such as perfusion defects in 13.0% of CTAP and non-pathologic enhancement in 19.1% of CTHA. CONCLUSION: With the use of spiral CT technique, the quantity of contrast material administrated in CTAP and CTHA can be considerably reduced, and the quality of CT images significantly improved. The detection rate of CTAP and CTHA is higher than that of biphase enhanced CT. Simultaneous use of both procedures may help decrease the false-positive rate, and increase the sensitivity of diagnosis for small hepatocellular carcinoma. PMID- 11776625 TI - [The value of "blood vessel convergency" sign in the diagnosis of small peripheral lung cancer]. AB - OBJECTIVE: To evaluate blood vessel convergency (BVC) sign in the radiologic diagnosis of small peripheral lung cancer. METHODS: A prospective thin-section CT pathology comparative study was done in 123 cases with solitary pulmonary nodules less than 3 cm in diameter including 83 peripheral lung cancera (adenocarcinoma 46, squamous-cell carcinoma 21, bronchiolo-alveolar-cell carcinomas 7, undifferentiated carcinoma 6, adenosquamous carcinoma 3) and 40 benign lesions. They were pathologically and clinically confirmed. Serial transverse sections of the surgically resected specimens were examined microscopically in 91 cases. Attention was focused on the imaging and histological manifestations of BVC. RESULTS: BVC was found in 54 (65.1%) peripheral lung cancers and in 8(20%) benign nodules (chi 2 = 22.75, P < 0.001). Histologically, the convergent vessels were shown to be dilated arterioles or venules. CONCLUSION: Blood vessel convergency can be regarded as a valuable sign for the diagnosis of small peripheral lung cancers. PMID- 11776623 TI - [In situ observation of apoptosis and proliferation in breast cancer and its precancerous lesions]. AB - OBJECTIVE: To investigate the effects of apoptosis and proliferation on malignant transformation of breast precancerous lesions by in situ observation. METHODS: The density and distribution of apoptotic cells were examined in 31 cases with breast cancer, 20 with dysplasia and 20 with hyperplasia, using TUNEL (TdT mediated dUTP nick end labeling) technique and immunohistochemical method respectively. Eight normal breast tissues were used as the control. RESULTS: In normal breast tissue, apoptotic cells were located at the lacteals and gland follicles, facing the cavity. The proliferating cells were located at the basal layer of mucosa. These characteristics of distribution were lost in breast cancer and precancerous lesions. The density of apoptotic cells and proliferating cells of dysplasia was significantly higher than that in breast cancer and normal mucosa, The density of apoptotic cells and proliferating cells in breast cancer was significantly higher than that in normal mucosa. The ratio of apoptotic to proliferating cells in hyperplasia and dysplasia was 1:1.3-1.4, 1:1.1-1.2 respectively, and 1:2.3-2.4 in breast cancer. CONCLUSION: Abnormality in cell apoptosis and proliferation may play important role in the genesis of breast cancer. PMID- 11776626 TI - [Radiotherapy for early anal cancer: a report of 27 cases]. AB - OBJECTIVE: To evaluate the results of radiotherapy for early stage anal cancer. METHODS: During 1960 through 1993, 27 patients with stage T1-2N0 anal cancer were treated by radiotherapy alone. Seven cases received pelvic irradiation plus local field boost, 20 cases received local field irradiation alone. Kaplan-Meier method was used in survival analysis. RESULTS: The overall 5-year survival rate in this series of patients was 79.1%. Eighteen of the 27 cases had their anal functions preserved. Local recurrence occurred in 7 cases and regional lymph node metastasis in one case. Five of them were salvaged, two by surgery and three by irradiation. CONCLUSION: Radiotherapy alone for early anal cancer is effective. Anal function is preserved in about two-thirds of the patients so treated. Local treatment failure can be salvaged by surgery or radiotherapy. PMID- 11776627 TI - [Clinicopathological characteristics and surgical treatment of primary neurogenic tumors of the mediastinum]. AB - OBJECTIVE: To study the clinical and histopathological characteristics, and surgical treatment of primary neurogenic tumors of the mediastinum. METHODS: The experience in diagnosis and treatment of 125 patients with primary neurogenic tumors of the mediastinum from Jan. 1965 to Dec. 1998 in our hospital was summarized. All patients were operated and pathologically confirmed. RESULTS: Primary neurogenic tumor accounted for 125(22.0%) of 568 patients with primary tumors of the mediastinum in the same period. The incidence of neurilemoma was 48.9% (61/125), neurofibroma 27.2% (34/125), ganglioneuroma 13.6% (17/125), and other rare tumors 10.4% (13/125, neurofibrosarcoma 4, ganglioneuroblastoma 3, chemodectoma 3, pheochromocytoma 2, and neuroblastoma 1). In this series, 78 patients did not have any subjective symptoms, and the tumors were found on routine physical checkup. In 117 patients, the tumors were located in the posterior mediastinum. In all bwt 2 patients, the tumor was resectable. The postoperative complication rate was 4.0% and operative mortality rate was 0.8%. The 3-year survival rate in patients with malignant tumors was 18.2%. CONCLUSION: The clinical characteristics and prognosis of primary neurogenic mediastinal tumors varies with their histopathology. Surgical operation is the first choice of treatment. PMID- 11776628 TI - [Adenocarcinoma of the urinary bladder: a report of 27 cases]. AB - OBJECTIVE: To analyze the therapeutic results of urinary bladder adenocarcinoma. METHODS: Twenty-seven urinary bladder adenocarcinoma patients were treated from 1970 through 1997. There were 12 cases of urachal adenocarcinoma and 15 cases of bladder adenocarcinoma. Hematuria with or without urinary tract irritation symptoms was the most common clinical manifestation. RESULTS: The overall 5-year survival rate was 25.9%. Among patients with urachal adenocarcinoma, 7 received extended partial bladder resection. None of them had local recurrence. Patients with bladder adenocarcinoma mainly received partial bladder resection, with which 4 developed local recurrence at the primary site. The 5-year survival rate of urachal adenocarcinoma and bladder adenocarcinoma was 33.3% and 20.0%, respectively. One patient of bladder adenocarcinoma with skin and inguinal lymph node metastases and 2 patients of urachal adenocarcinoma with lung metastasis treated with chemotherapy and radiotherapy survived 24, 28 and 60 months, respectively. CONCLUSION: Extended partial bladder resection is the treatment of choice for urachal adenocarcinoma while radical cystectomy for bladder adenocarcinoma. Comprehensive therapy should be given to patients with metastatic or recurrent disease to improve survival. PMID- 11776629 TI - [The role of surgery in the management of thyroid lymphoma]. AB - OBJECTIVE: To evaluate the role of surgery in the management of thyroid lymphoma. METHODS: A retrospective analysis was performed of 14 patients with thyroid lymphoma treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy Medical Science from 1964 to March 1998. There were 5 males and 9 females, with a median age of 54 years (range 15-75). There were 4 cases in stage IEA, 9 in stage IIEA, 1 in stage II EB. Fine needle aspiration biopsy was performed in 1 case, excision biopsy in 4, thyroid lobectomy in 8, and total thyroidectomy in 1. Radiotherapy was used alone in 4 patients, chemotherapy alone in 2, radiotherapy combined with chemotherapy in 7, no postoperative treatment in 1. RESULTS: All but 1 patients were histopathologically diagnosed as non Hodgkin's lymphoma. It was of B cell origin in 11 cases, T cell origin in 2. Seven patients were alive without evidence of recurrent disease at follow-up, ranging from 5 to 112 months. Three patients died of lymphoma, 1 died of treatment complication, 2 died of other diseases, and 1 lost from follow-up. The major surgical resection did not appreciably affect survival. CONCLUSION: Radiotherapy or chemotherapy, alone or in combination, is the treatment of choice for thyroid lymphoma. Surgical resection combined with radiotherapy or chemotherapy may be beneficial to survival in patients with intrathyroid lymphoma. It is otherwise limited to make a tissue diagnosis. PMID- 11776630 TI - [Relationship between extent of tumor resection and prognosis: an evaluation in 533 cases of gastric cancer]. AB - OBJECTIVE: To evaluate prognosis of patients with stomach cancer based on the extent of tumor resection. METHODS: Five hundred and thirty-three cases of gastric cancer resected from 1980 through 1990 were divided into 3 categories A, B, and C, in the order of decreasing completeness of tumor resection as set forth in the 12th edition of "Rules for Gastric Cancer in Japan". RESULTS: There were 157 cases in category A, 209 cases in category B and 167 cases in category C. Their survival rate was 80.9%, 34.9%, and 9%, respectively. In category A and B, the depth of tumor invasion and lymph node metastasis were the major factors affecting survival rate. In the presence of lymph node metastasis, prognosis was dependent on which station (D1-D3) of lymph nodes dissected. In category B, if dissection covered D3 but metastasis was limited to I or II, the 5-year survival rate was 48%; if lymph node dissection performed was limited to the same station of lymph nodes where metastasis occurred, the 5-year survival rate dropped to 22.4% (P < 0.05). In case cancer left over at the cutting edge, the completeness of resection might drop from category A or B to C, and the 5-year survival rate correspondingly decreased to 6% and 12.2%, respectively. CONCLUSION: In order to ensure completeness of tumor resection, lymph node station dissected should be farther than that with metastasis, and the distance between the tumor and the cutting edge should be long enough to prevent residual tumor left behind. PMID- 11776631 TI - [Surgical treatment of esophageal leiomyosarcoma: a review of the literature and report of 11 cases]. AB - OBJECTIVE: To discuss the clinical biocharacteristics, diagnosis, operation and prognosis of esophageal leiomyosarcoma (ELS). METHODS: Clinical materials and follow-up results of 11 surgically treated ELS patients were analyzed. RESULTS: All 11 cases received radical resection of tumor. The 5-year survival rate was 54.5% (6/11). Grossly, two types of ELS were observed: the polyp form (4 cases) and invasive form (7 cases). The 5-year survival rate was 75.0% and 42.9%, respectively. Two patients died of local recurrence, another 2 cases died of distant metastasis. CONCLUSION: In patients with ELS surgically treated, prognosis of polyp form ELS is better than that of invasive form ELS. Local recurrence and distant metastasis are the major cause of death. PMID- 11776632 TI - [Effect of rhTFAR19 protein on cell cycle and apoptosis of MCF-7 induced by gamma ray]. AB - OBJECTIVE: To investigate the effect of protein product of TFAR19, an apoptosis related gene previously cloned from leukemia cell line TF-1 cultured in medium deprived of growth factor, on cell cycle and apoptosis of human breast cancer induced by gamma-ray. METHODS: Cell morphology, fluorescence microscopy, laser scanning confocal microscopy, single-cell gel electrophoresis (SCGE) and flow cytometry (FCM) were applied to study cell cycle and apoptosis of breast cancer cell line MCF-7. RESULTS: rhTFAR19 protein itself had no effect on cell cycle arrest and apoptosis of MCF-7 cell induced by gamma-ray. When MCF-7 cells were pretreated with 10 micrograms/ml rhTFAR19 and then irradiated with 12 Gy gamma ray, cell apoptosis was observed. It was characterized morphologically by chromatin condensation, nucleoar disintegration, formation of apoptotic bodies, and typical "cornet" on SCGE. CONCLUSION: TFAR19 protein has no apparent effect on MCF-7 cell cycle induced by gamma-ray. However, it synergizes with gamma radiation in the induction and enhancement of apoptosis. PMID- 11776633 TI - [Difluoromethylornithine synergizes with antisense bcl-2 RNA in the induction of apoptosis of HL60 cells]. AB - OBJECTIVE: To study the combined effect of difluoromethylornithine (DFMO) and bcl 2 antisense RNA in the induction of apoptosis of HL60 cells. METHODS: HL60 cells were transfected with recombinant retroviral vector expressing bcl-2 antisense RNA. The growth characteristics of transfectants were studied by morphological observation, growth curve, FCM analysis, colony formation in soft agar, DNA electrophoresis, molecular hybridization and immunocytochemical staining. RESULTS: The recombinant retroviral vectors expressing bcl-2 antisense RNA and the cell line producing recombinant virus were constructed. Although the expression of bcl-2 at mRNA and protein levels in the HL60 cells transfected with antisense bcl-2 were down-regulated, there was no change in cell growth, cell cycles and expression of ornithine decarboxylase (ODC) compared with the parental cells albeit some decrease in colony formation. In addition, transfection with antisense bcl-2 did not induce marked apoptosis whereas treatment of the transfectant with low concentration (0.2 mmol/L) of DFMO resulted in enhanced expression inhibition of bcl-2 protein, inhibition of cell growth and induction of apoptosis. CONCLUSION: DFMO synergizes with antiense bcl-2 RNA in the induction of apoptosis of HL60 cells. PMID- 11776634 TI - [Fibronectin induces matrix metalloproteinase-2 expression in ovarian cancer cells]. AB - OBJECTIVE: To investigate the effects of extracelluar matrix proteins on matrix metalloproteinases (MMPs) expression by cancer cells, and the underlying mechanisms. METHODS: Following stimulation of SKOV3 ovarian cancer cells by fibronectin, MMPs secretion and cellular mRNA contents were assayed by gelatin zymography and RT-PCR, respectively. The activity of MMP-2 promoter was monitored by cellular luciferase activity after the cells were transfected with MMP-2 promoter-luciferase construct. Cellular p53 contents were determined by Western blot analysis. RESULTS: Fibronectin (5 micrograms/ml) was found to stimulate the secretion of MMP-2 but not MMP-9 by SKOV3 cells. The stimulation was enhanced with the increase in fibronectin concentration. When SKOV3 cells were treated with 10 micrograms/ml fibronectin for 1 hr, the cellular MMP-2 mRNA dramatically increased. However, with increase in stimulation time, MMP-2 mRNA content decreased. Fibronectin induced an increase in luciferase activity in cells transfected with MMP-2 promoter construct, whilst curcumin (50 mumol/L), a potent transcription factor AP-1 inhibitor, could not block the fibronectin-induced increase in MMP-2 promoter activity. Fibronectin also induced an increase in p53 content of SKOV3 cells. CONCLUSION: Fibronectin stimulates ovarian cancer cells to secret MMP-2 via its enhancing effect on MMP-2 promoter activity with resultant increase in MMP-2 transcription. The effect might involve a pathway associated with p53 but independent of AP-1. PMID- 11776635 TI - [Therapeutic effect of 5-fluorocytosine on cytosine deaminase gene transduced Wilms' tumor xenograft in nude mice]. AB - OBJECTIVE: To study the effect of 5-fluorocytosine (5-FC) as prodrug in the treatment of Wilms' tumor xenografts transduced with cytosine deaminase (CD) gene. METHODS: An in vivo model of a poorly differentiated Wilms' tumor transplanted in nude mice was established. Expression adenoviral-vector of CD gene (Ad/CMV-CD) or lac gene (Ad/CMV-lac) was transduced to the tumor xenografts by intratumoral injections. Expression of the transduced genes were confirmed by RT-PCR. Mice with Wilms' tumor xenograft were treated with 5-FC (500 mg.kg-1.d-1 x 10 d). Tumor growth was monitored. RESULTS: The growth of tumor xenografts transduced with lac gene grew as quick as the untransduced ones. In contrast, the growth of the tumor xenografts transduced with CD gene was significantly inhibited as compared to untransduced and lac gene transduced xenografts. The average rate of inhibition was 65% according to the tumor weight at 8 wk. Cell necrosis was observed in the CD gene transduced tumors. CONCLUSION: Intratumoral cytosine deaminase gene transduction followed by systemic 5-fluorocytosine is effective in the treatment of Wilms' tumor. PMID- 11776637 TI - [Construction of adenovirus vector for human p27kip1 gene and its expression]. AB - OBJECTIVE: To study the effects of exogenous p27kip1 gene on cell cycle and proliferation. METHODS: E1 substitutive adenovirus vector pAxlcw containing human p27kip1 cDNA (Cihp27kip1) under the transcriptional control of CMV promoter was constructed and then cotransfected with Ad5 adenovirus DNA-terminal peptide complex EcoT221-digested into 293 cells for preparing p27kip1 recombinant adenovirus Adhp27kip1. After infecting HeLa cells for 24 h, the exogenous p27kip1 protein expression in HeLa cells and its effects on cell cycle and proliferation were determined by Western blot, FACS and MTT assay. RESULTS: The titers of resultant recombinant adenoviruses was 1.7 x 10(9) pfu/ml. p27kip1 protein was over-expressed in HeLa cells infected with p27kip1 recombinant adenovirus for 24 h, resulting in blockage of cell cycle transition from G1 phase to S phase and inhibition of cell proliferation. CONCLUSION: p27kip1 recombinant adenoviruses prepared in this study can efficiently transfer p27kip1 gene into HeLa cells and over-express p27kip1 protein in the infected cells. Adhp27kip1 can be used as an agent for gene therapy. PMID- 11776636 TI - [Safety evaluation of Ad-ASmyc in vitro and in vivo]. AB - OBJECTIVE: To assess the safety of adenovirus-mediated transfer of anti-sense c myc (Ad-ASmyc). METHODS: RT-PCR was used to detect the transcription of Ad-ASmyc in HeLa cells infected with extracts from HeLa cells previously infected with Ad ASmyc. Cell count was used to observe the effects of Ad-ASmyc on the growth of normal human fetal lung diploid cell line 2BS. Ad-ASmyc was given to 2 groups of Balb/c mice by intraperitoneal injection at a dosage of 10(7) pfu and 10(9) pfu respectively. Blood samples were obtained from the mice for liver and renal function tests. PCR was used to screen the vital organs for the presence of adenovirus DNA. Microscopic examination of the vital organs was performed to observe the pathogenicity of Ad-ASmyc. RESULTS: As a replication-defective virus, Ad-ASmyc could infect 2BS cells effectively, but did not inhibit 2BS cell growth. No mouse died and no signs of general toxicity following intraperitoneal injection of Ad-ASmyc were observed. In mice injected with 10(9) pfu Ad-ASmyc, the adenoviral vector was found in the liver, spleen, kidney, and stomach. On day 6 and day 12 after injection, mild inflammatory infiltration of mononuclear cells was observed. CONCLUSION: The use ofadenoviral vector for antisense c-myc gene transfer in vitro and in vivo is considered to be safe for clinical trial. PMID- 11776638 TI - [In vitro study of radiation sensitizing effect of hydroxycamptothecin]. AB - OBJECTIVE: To study the radiation sensitizing effect of hydroxycamptothecin (HCPT) on human stomach adenocacinoma and nasopharyngeal carcinoma. METHODS: Human stomach cancer cell line BGC823 and nasopharyngeal cancer cell line CNE-1 were treated in vitro with different doses of radiation alone or radiation followed by HCPT (2 micrograms/ml) for 4 h. Colony forming assay was used for survival fraction analysis. Single-hit multitarget model was used to plot survival curve. RESULTS: The value of D0, Dq and N of BGC823 cells received radiation treatment alone was 1.17 Gy, 1.91 Gy and 5.14 respectively. That of BGC 823 cells received radiation plus HCPT was 0.95 Gy, 0.01 Gy and 1.01 respectively. The sensitization enhanecment (SER) ratio was 1.23 (1.17/0.95). Similar results were obtained for CNE-1 cells treated with radiation alone or in combination with HCPT, with an SER of 1.68. CONCLUSION: HCPT has been shown a radiosensitizing effect in vitro on gastric and nasopharyngeal cancer cells. PMID- 11776639 TI - [Cytokeratin 13 gene expression in human nasopharyngeal carcinoma]. AB - OBJECTIVE: To investigate the possible pathogenetic role of cytokeratin 13 (CK13) gene expression in human nasopharyngeal carcinoma (NPC). METHODS: Tissue samples taken from a total of 40 cases of NPC and 8 cases of chronic inflammation of nasopharyngeal epithelium (CINE) were immunohistochemically studied for CK13 protein expression. Northern blot hybridization was used to detect CK13 gene at mRNA level in 32 of the 40 NPC and in 8 CINE cases. Correlations of CK13 expression with the clinical features of NPC were also investigated. RESULTS: Significantly stronger immunoreactivity for CK13 protein was shown in CINE than in NPC tissues (P < 0.01), so did it at mRNA levels. Significantly higher CK13 expression was demonstrated in patients with cervical lymph node metastasis, as compared to those without (P < 0.05). However, no significant correlation between CK13 expression and clinical staging of the disease. CONCLUSION: The decreased expression of CK13 in NPC suggests that differentiation disturbance of the nasopharyngeal epithelium might play a role in the pathogenesis of NPC. PMID- 11776640 TI - [Clinical implications of telomerase activity in breast cancer fine-needle aspirates]. AB - OBJECTIVE: To study the telomerase activity in samples of breast fine-needle aspirates, its clinical implications, and possible association with expression of PR, ER, PCNA, c-erbB2 and p53. METHODS: Ninetynine fine needle aspirates from breast cancers in 83 patients, 12 from benign lesions and 4 from inflammation of the breast, were examined for telomerase activity by a PCR-based telomere repeat amplification protocol (PCR-TRAP). In 35 breast cancer tissue specimens, expression of PR, ER, PCNA, c-erbB2 and p53 were examined by immunohistochemical staining. RESULTS: Among 83 fine-needle aspirates from breast cancer, telomerase activity was detected in 61 of 69 cytology-possitive specimens and in 5 of 7 cytology-suspicious specimens and in 4 of 7 cytology-negative specimens, with an overall positive rate of 84.3% (70/83). The concordance rate of telomerase detection and cytologic examination was 77.1% (64/83). Of 12 fine-needle aspirates from patients with benign breast lesions, 4 were telomerase positive, but 4 aspirates from inflammed breast were all negative. Telomerase activity of breast cancer aspirates did not correlate with histologic type, lymph node status, tumor size and clinical stage, nor did it correlate with PR, ER status and PCNA and c-erbB2 expression. However, negative correlation was found between telomerase activity and accumulation of p53 proteins. CONCLUSION: Detection of telomerase in breast fine-needle aspirates complementary to cytological examination is useful in the diagnosis of breast cancer. Its possible association with p53 accummulation needs further study. PMID- 11776641 TI - [Tumor infiltrating dendritic cells in relation to prognosis of lung cancer]. AB - OBJECTIVE: To study the degree of infiltration of dendritic cells in lung cancer in relation to prognosis. METHODS: S-100 protein as the marker of tumor infiltraing dendritic cells (TIDC) was stained immunohistochemically in lung cancer specimens. The degree of infiltration was considered mild and marked according to the criteria reported by Furukawa. The survival rate was obtained by Log-rank test of the data. RESULTS: In 15 of 38 adenocarcinomas, whose TIDC infiltration was marked, the five-year survival rate was 60.0%, while in 23 with mild TIDC infiltration, the five-year survival rate was 21.7% (P < 0.01) Quite similar data were obtained from 44 squamous-cell carcinomas. Significantly higher five-year survival rate (61.1%) was observed in those with marked TIDC than those with mild infiltration (19.2%). CONCLUSION: The degree of TIDC infiltration is positively correlated with the survival rate of lung carcinoma patients. PMID- 11776642 TI - [Expression of MAGE-3 gene product in non-small cell lung cancer]. AB - OBJECTIVE: To study the expression of MAGE-3 antigen in non-small cell lung cancer (NSCLC). METHODS: The expression of MAGE-3 antigen was examined in formalin fixed, paraffin embedded sections of NSCLC by LSAB immunohistochemical technique. RESULTS: MAGE-3 antigen was detected in 31 of 104 (29.8%) patients with primary NSCLC. The frequency of MAGE-3 expression was significantly correlated to the absence of metastasis (P < 0.05) and better survival rate (P < 0.01). There was no significant relationship between MAGE-3 expression and histological type of NSCLC. CONCLUSION: MAGE-3 antigen expression in NSCLC correlates with better prognosis. It is a candidate molecular target for specific immunotherapy for NSCLC patients. PMID- 11776643 TI - [Relationship between the expression of cell cycle regulators and microsatellite instability in colorectal carcinomas]. AB - OBJECTIVE: To explore the relationship between the expression of cell cycle regulators and microsatellite instability (MSI) in colorectal carcinomas(CRC). METHODS: The expression of cell cycle regulators cyclin D1, P16, P21WAF1/CIP1, P53, Rb and PCNA were detected by immunohistochemical staining, and MSI at six microsatellite loci (D18S34, D17S799, D5S409, TCF-2, Rb and P53) were examined by PCR-SSLP in 56 cases of colorectal carcinomas. RESULTS: The overall positive rate of MSI of CRC was 44.6% (25/56). MSI was positive at 1 locus in 7 cases, at 2 and more than 2 loci in 18 cases. In CRC with MSI, the positive rate of cyclin D1 and P53 protein was significantly lower, while that of P21 protein was significantly higher than those without MSI (P < 0.05). The positive rate of P16 in CRC with MSI was higher than those without MSI. The expression of Rb proteins was similar in frequency in CRC with or without MSI. CONCLUSION: Overexpression of P21 may play an important role in MSI genesis in CRC. It may also be related to decreased expression of cyclin D1 and P53 and overexpression of P16. PMID- 11776645 TI - [The value of serum alpha-L-fucosidase activity in the diagnosis of primary liver cancer]. AB - OBJECTIVE: To analyse the value of serum alpha-L-fucosidase (AFU) in the diagnosis of primary liver cancer (PLC). METHODS: Serum AFU was studied in 141 patients with PLC, 17 patients with secondary liver cancer, 16 patients with cirrhosis, and 30 controls. Rank correlation analysis was used to assess the relation between value of AFU activity and TNM staging. The results were compared to those of serum AFP determination. RESULTS: AFU was increased in 108 of 141 (76.6%) patients. The positive rate was statistically different from that in patients with secondary liver cancer, cirrhosis, and that in normal individual. The AFU level was correlated with TNM stage. In 25 PLC patients with AFU > 500 nmol.L-1.S-1, the average survival time was only 71 days. In 36 PLC patients who had received effective treatment, the serum AFU decreased to a significantly lower level than that examined before treatment. The positive rate of AFP in PLC patients was 64.5%. It rose to 86.2% if both parameters were used. CONCLUSION: AFU is a useful marker of PLC for diagnosis and posttreatment monitoring. PMID- 11776644 TI - [Mechanisms of drug resistance of primary renal cell carcinomas and their clinical significance]. AB - OBJECTIVE: By multifactorial analysis, to study the mechanisms of drug resistance of primary renal cell carcinomas (RCC). METHODS: Seventy cases of paraffin embedded RCC tissue sections were examined for the expression of P-gp, GST-pi and Topo II by immunohistochemical staining. RESULTS: There was 65.7% of RCC with expressed P-gp. Its Expression was stronger in late than in early stage of RCC. GST-pi was expressed in 41.1% RCC, but the magnitude of expression did not correlate with differentiation, type and stage of RCC. All the RCC examined had Topo II expression. Its expression level was lower than that of cancer of the intestine and lung. Among the 70 cases of RCC, 31.4% of them expressed at least one of the 3 drug-resistance parameters. Co-expression of two drug-resistance parameters was observed in 42.8% of the cases that of 3 drug-resistauce parameters in 22.9% of the cases. CONCLUSION: Drug resistance is of common occurrence in RCC. To achieve better therapeutic efficacy, appropriate chemotherapeutic agents should be given to patients with low expression of P-gp and GST-pi but high expression of Topo II. PMID- 11776646 TI - [Relationship between blast crisis of chronic myeloid leukemias and abnormality of p16 and calcitonin genes]. AB - OBJECTIVE: To study the relationship between homozygous deletions of p16 gene and calcitonin hypermethylation and chronic myeloid leukemia (CML) blast crisis. METHODS: Semiquantitative multiplex polymerase chain reaction (PCR) was used to detect homozygous deletions of p16 gene and semiquantitative PCR to detect calcitonin gene hypermethylation in 53 CML patients. RESULTS: In 53 CML patients, homozygous deletion of p16 gene was found in none of them in chronic phase, while in 6.3% (1/16) of them in myeloid blast crisis, 66.7% (8/12) in lymphoid blast crisis, and 2/5 (40%) in mixed cell blast crisis. Calcitonin gene hypermethylation was found in 10% (2/20), 68.8%(11/16), 16.7%(2/12), and 40% (2/5), respectively. CONCLUSION: There is intimate relationship between homozygous deletions of p16 gene and CML in lymphoid blast crisis, between calcitonin gene hypermethylation and CML in myeloid blast crisis. Moreover, abnormality of both genes may be associated with mixed cell blast crisis in CML patients. Simultaneous detection of the two genes help early pickup CML patients in blast crisis. PMID- 11776647 TI - [Drug resistance of acute promyelocytic leukemia (APL) to all-trans retinoic acid (ATRA) and its reversion]. AB - OBJECTIVE: To study the mechanism of drug resistance of APL to ATRA and the methods of reversion. METHODS: ATRA-resistant HL60 cell line and bone marrow (BM) leukemia cells from recurrent APL patients who did not respond to ATRA treatment were used in this study. Multiple drug resistance gene (mdr1) expression was determined by RT-PCR and flow cytometry. Cell proliferation and differentiation were assessed by MTT uptake and NBT reduction respectively. RESULTS: The response of ATRA-resistant HL60 and APL cells from recurrent patients to the differentiation inducing activity of ATRA was significantly reduced, and ATRA had little effect on cell proliferation. Expression of mdr-1 was nagative in ATRA resistant HL60 cells. It was negative in resistant APL cells even after ATRA treatment. Arsenic trioxide and homoharringtonine (HHT) could inhibit proliferation of HL60 and ATRA-resistant HL60 cells, indicating no cross resistance with ATRA. Interferon alpha (IFN-alpha) and PGE1 could significantly inhibit proliferation of ATRA-resistant HL60 cells and restore cell differentiation induced by ATRA. CONCLUSION: Drug resistance of APL to ATRA is not related to mdr-1. It can be reversed by IFN-alpha. There is no cross resistance between HHT or arsenic trioxide and ATRA. PMID- 11776648 TI - [Apoptosis and apoptosis-related gene expression in nasopharyngeal carcinoma]. AB - OBJECTIVE: To study apoptosis and expression of apoptosis-related genes in nasopharyngeal carcinoma(NPC). METHODS: Paraffin-embedded tissue blocks from 73 cases of NPC and 20 cases of chronic nasopharyngitis were used in this study. Using terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (Tunel) and immunohisytochemistry S-P method, the apoptotic rate (AR) and expression of p16 and bcl-2 protein were examined. RESULTS: Few apoptotic cells were found in NPC, the AR significantly lower than that of chronic nasopharyngitis (P < 0.01). The frequency of expression of p16 and bcl-2 in NPC was 28.8% (21/73) and 81.2% (59/73), respectively, while that in chronic nasopharyngitis was 90% (18/20) and 15% (3/20), respectively. In NPC, expression of p16 was positively correlated, while bcl-2 negatively correlated with the AR (P < 0.01). According to 3-year follow up, the survival rate was higher in NPC patients with AR > 2.0 and negative bcl-2 expression, whereas that was higher in patients with positive expression of p16. CONCLUSION: Apoptosis is inhibited in NPC which may be related to p16 and bcl-2 gene dysregulation. Apoptosis correlates with prognosis in NPC patients. PMID- 11776649 TI - [Correlation study of the longest diameter of gastric cardia cancer and its prognosis]. AB - OBJECTIVE: Based on the longest diameter of cancer of gastric cardia, to formulate a new way of staging for better assessment of prognosis. METHODS: A total of 1,536 cases of resected carcinoma of the gastric cardia through left thoracic approach was statistically analyzed using STATA 5.0 software. The survival rate was estimated using life table method. The difference in survival rate between groups was evaluated by the log-rank test. The ratio difference between groups was evaluated by chi 2 test. RESULTS: The longest tumor diameter was divided into 6 grades according to its length: grade I, < 2 cm; grade II, 2 cm-< 4 cm; grade III, 4 cm-< 6 cm; grade IV, 6 cm-< 8 cm; grade V, 8 cm-< 11 cm and grade VI, > or = 11 cm. The 5-year survival rate was 61.5% in grade I, 44.4% in grade II, 26.4% in grade III, 20.5% in grade IV, 16.1% in grade V and 5.7% in grade VI, respectively. There was statistically significant difference (P < 0.05) in 5-year survival rate between 2 grades from grade II to grade VI. CONCLUSION: The longest tumor diameter is of prognostic significance in cancer of gastric cardia. PMID- 11776650 TI - [Spiral CT features of hepatocellular caicinoma]. AB - OBJECTIVE: To analyze the features of two-phase spiral scanning in 54 cases of hepatocellular carcinoma and to evaluate its usefulness in diagnosis and differential diagnosis. METHODS: Precontrast and postcontrast CT scans of the whole liver in all cases were carried out with GE-Hispeed Advantage spiral CT scanner. The arterial phase scanning was started at 25 sec after injection of contrast medium and the portal venous phase scanning at 70 sec. RESULTS: In the 54 cases examined, 72 lesions were found in the arterial phase. In 28 of these lesions, it was enhanced homogeneously, while in 40 lesions, the enhancement was not homogeneous. Supplying artery could be seen in 4 of them. The remaining 4 lesions had no enhancement. There were 62 lesiosns with low density in portal venous phase. Portal vein tumor thrombus was seen in 8 cases, and pseudocapsule was observed in 7 lesions. CONCLUSION: Two-phase spiral CT scanning is of value in the diagnosis and differential diagnosis of hepatocellular carcinoma. PMID- 11776651 TI - [Clinical observation of palitaxel in the treatment of gynecologic malignant tumors]. AB - OBJECTIVE: To observe the therapeutic effect of palitaxel. METHODS: Of 37 cases, 33 were treated when tumor recurrence occurred after surgery or chemotherapy. There were 27 cases with ovarian cancer, 6 with fallopian tube cancer. 3 with cervix cancer, and 1 with endometrium cancer. In all cases, diagnosis was confirmed by histopathology. Palitaxel (135-150 mg/m2) was administered i.v. or i.p. once every three werks in combination with cisplatin (PDD) 60 mg/m2 and cyclophosphamide (CTX) 60 mg/d. Antihistaminics and antiemetic were given prior to palitaxel. The results of treatment were compared with those in 37 cases treated in the some time period with PAC or VBP regimen. RESULTS: The overall median survival time of the control group was 4 months, and 8.5 months in the palitaxel treated group (P < 0.001). The response rate was 18.9% and 48.6% respectively (P < 0.005). The major toxic effects was myelosuppression and alopecia. CONCLUSION: Palitaxel is effective in the treatment of advanced gynecological tumors. PMID- 11776652 TI - [Clinical observation of taxotere in the treatment of advanced non-small-cell lung cancer and breast cancer]. AB - OBJECTIVE: To observe the response rate and toxic reaction of taxotere in the treatment of advanced NSCLC and breast cancer. METHODS: A total of 24 cases was included in the study. Taxotere 75 mg/m2 i.v. drip for 1 hour; dexamethasone 8 mg bid 24 hour before taxotere, and continued for 3 days. For NSCLC, the taxotere was combined with DDP 90 mg/m2; for breast cancer, it was combined with ADM 40 mg/m2. The second treatment cycle was given after 3 weeks. At last 2 cycles were given. RESULTS: In 15 NSCLC patients, there were 6 PR, 7 NC and 2 PD. In 9 breast cancer patients, there were 2 CR, 6 PR and 1 NC. The major toxic reactions were neutropenia, diarrhea, fatigue, muscle pain and alopecia. Grade 3 and grade 4 neutropenia occurred in 9 and 4 cases, respectively. Decrease in hemoglobin and thrombocytopenia were mild. Diarrhea occurred in 19 cases and allergic reaction in 1 case. CONCLUSION: Taxotere is effective in the combined treatment of advanced NSCLC and breast cancer. The toxic reactions are tolerable. PMID- 11776653 TI - [Carcinoma of the vulva: a report of treatment]. AB - OBJECTIVE: To analyse the outcome of various treatments for vulvar cancer and to investigate the characteristics of the recurrence and metastasis. METHODS: A total of 309 patients with carcinoma of vulva were analyzed retrospectively. RESULTS: The overall 5-year survival rate was 67.9%. That for stage I, II, III and IV was 86.9%, 82.5%, 59.2% and 43.6%, respectively. Treatment failure was seen in 49.8% of the treated cases, and it occurred within 2 years after primary treatment in the majority of the cases. Inguinal and pelvic recurrences, and distant metastases occurred within 2 years, while local recurreuce mostly after 2 years. Recurrence rate was not related to age of the patients. For stage I cancer, there was no difference in the results of different methods of treatment, but for stage II cancer, wide local resection plus inguinal lymphadenectomy was a better choice. In patients with regional lymph node metastases treated by nodal resection, it was less likely to recur than did radiotherapy. If no nodal involvement, the outcome of the two types of treatment was not different. Higher dose of radiation (Dm > or = 60 Gy) was better than lower dose (40-50 Gy) for prevention of recurrence. CONCLUSION: For early stage vulvar cancer, in addition to radical resection of vulva, preventive dissection of inguinal lymph nodes, or full dose radiation of the inguinal region, leads to better therapeutic results. For advanced cases, radical resection of the primary tumor with pre- and post operative radiation, and inguinal lymph nodal disection, whenever possible, should be performed. PMID- 11776654 TI - [Microsurgical treatment of medially located tumors of the middle skull base]. AB - OBJECTIVE: To report the results of microsurgical treatment of tumors medially located in the middle skull base. METHODS: The preoperative MRI features, operative approaches, results of operation and postoperative complications in 26 cases were reviewed. RESULTS: Total resection of the tumors was achieved in 12 cases, subtotal resection in 9 cases, partial resection in 6 cases. Two patients died of operation. Cranial nerve palsy remained unchanged in 5 cases and became exacerbated in 5 cases. Clinical improvement was observed in 15 cases. CONCLUSION: The combined frontotemporal-zygomatic approach to remove medially located tumors of the middle skull base is adequate. PMID- 11776655 TI - [Purification of hsp70 and its immunoprotective effect against mouse hepatoma]. AB - OBJECTIVE: To purify hsp70 protein and observe its anti-tumor effect on mouse H22 hepatoma. METHODS: Cytosolic hsp70 protein of heat treated H22 cells was purified successively by chromatographic procedures, including DEAE 52-cellulose, ConA sepharose 4B and ADP-argarose chromatography. The molecular weight and the identity of the purified hsp70 protein were confirmed by SDS-PAGE and Western blot. Tumorigenicity of H22 hepatoma was examined in purified hsp70-treated C3H mice. RESULTS: A sharp stained protein band with a molecular weight of about 70 kD was obtained and shown to be hsp70 as confirmed by Western blot. In C3H mice challenged with H22 hepatoma, tumor developed in 6 of 6 mice while in hsp70 pretreated mice, none of the 6 H22 challenged mice developed tumor. Nevertheless, C57BL/6 mice pretreated with hsp70 or RPMI 1640 all developed tumor upon challenge with EL-4 lymphoma. CONCLUSION: The results suggest that the immunoprotective effect of hsp70 protein is due not to hsp70 per se, but rather to the specific antigenic peptides it carries. PMID- 11776656 TI - [Increase in thermosensitivity of cervical cancer and ovarian cancer cells by HSP70 antisense oligodeoxynucleotides]. AB - OBJECTIVE: To investigate the thermosensitizing effect of HSP70 antisense oligodeoxynucleolides (ODN) on cervical and ovarian cancer cells. METHODS: Cervical cancer cell line Hela and ovarian cancer cell line MCAS were used to study their sensitivity to heat (42 degrees C, 1 hr) treatment. Heat-induced changes in cell viability was assessed by colony formation assay and apoptosis by cell morphology, agarose gel electrophoresis and flow cytometry. RESULTS: Thermosensitivity of Hela and MCAS cells pretreated with HSP70 antisense ODN was increased as compared to cells treated with heat alone. The increase was antisense dose dependent. Although heat treatment or antisense ODN did induce apoptosis of HeLa and MCAS cells, the percentage of apoptotic cells was significantly increased when both heat and antisense ODN were applied. The effect was dependent on the dose of HSP70 antisense ODN. CONCLUSION: The thermosensitivity of ovarian cancer cells and cervial cancer cells can be increased by HSP70 antisense oligomer. Apoptosis may be involved in the increase in thermosensitivity. PMID- 11776657 TI - Median nerve compression at the wrist: is it ever unilateral? AB - OBJECTIVE: Carpal Tunnel Syndrome (CTS) is commonly bilateral, but symptoms and EMG/NCS abnormalities may be seen unilaterally. This study was designed to determine whether there are any subclinical nerve conduction abnormalities on the "uninvolved" side. DESIGN: Statistical analysis of electrodiagnostic data. SETTING: Outpatient academic electrodiagnostic laboratory. PATIENTS: Twenty-two successive patients referred for bilateral upper extremity NCS/EMG with no symptoms or physical signs of CTS and totally normal results, and ten successive patients with an EMG/NCS diagnosis of CTS on one side, and completely normal EMG/NCS on the contralateral side. RESULTS: The median motor and sensory latencies at the wrist were significantly longer in the contralateral "uninvolved" limb than normals (median motor latency 3.75 vs. 3.30 msecs, p = 0.0005, median sensory latency 3.40 vs 3.00 msecs, p = 0.0002). Median sensory amplitude was smaller in the contralateral limb (30.5 uV vs. 41.5 uV, p = 0.0062). The (median-radial) D1 sensory latency difference was greater in the contralateral wrist (0.2 vs. 0.0 msecs, p = 0.0217). The (median-ulnar) sensory latency difference was not significantly increased (0.15 vs. 0.10 msecs, p = 0.2020). CONCLUSIONS: The contralateral limbs of patients with unilateral CTS show significant differences from normals in 4 out of 5 nerve conduction parameters. There is evidence of frequent subclinical median nerve compression in this group. PMID- 11776658 TI - Sacral reflexes normal values with monopolar short needle electrodes recording. AB - To reduce patients discomfort and improve reliability in pelvic floor neurophysiological studies we examined 28 normal subjects employing short monopolar electrodes. The technique proved to be reliable and less discomfort to the patient than the traditional concentric needle method. Data were tested for Gaussian distribution and tolerance limits for normality were assessed. Our data suggest that use of monopolar instead of concentric needle electrodes may be suitable for pelvic floor examination. PMID- 11776659 TI - Prognostic value of lower limb motor evoked potentials for motor impairment and disability after 8 weeks of stroke rehabilitation--a prospective investigation of 100 patients. AB - We investigated 100 patients with a one-sided, functionally relevant hemiparesis after stroke. Motor evoked potentials (MEPs) were obtained from the anterior tibial muscle four or more weeks after the insult as well as after an eight week period of inpatient rehabilitation. The MEP results were correlated with motor deficit, walking ability, and activities of daily living (ADLs). Patients with loss of MEP had lower scores on the Motricity Index (MI) both at the beginning and at the end of the rehabilitative treatment (p < 0.001) and also gained fewer points on the MI than patients with preserved MEP. This was the case even when analyzing the lower limb scores alone (p < 0.001 before treatment, p = 0.003 after eight week rehabilitation). When the MEP was preserved, patients were more likely to regain independence in walking (specificity 0.67, positive predictive value 0.96) and stair climbing (specificity 1.0, positive predictive value 1.0). Patients with preserved MEP also scored higher on global outcome scales such as Barthel Index (BI), Functional Independence Measure (FIM) and Glasgow Outcome Scale (GOS). However, these differences did not reach statistical significance (p > 0.05). According to our results, MEPs of the lower extremity are of predictive value for the rehabilitative treatment of patients in the postacute phase after stroke. This is especially true for the extent of the motor impairment and walking ability. The utilization of MEPs for prediction of future levels of disability and handicap is limited and only useful taking into consideration other clinical and diagnostic findings as well as the patients' cognitive, emotional and social state. PMID- 11776660 TI - Median nerve evoked responses: stimulation modalities for midlatency cortical components. AB - PURPOSE: Median nerve somatosensory evoked responses (MnSSER) are frequently used clinically and scientifically. However, the stimulus-response interrelationship has not been documented for the midlatency components. Therefore we investigated the spinal and cortical midlatency MnSSER, to document the effect of different stimulus intensities. METHODS: Spinal and midlatency MnSSER were recorded following percutaneous electrical stimulation of the median nerve at the wrist in 32 neurological healthy females. Three different stimulation intensities were applied: threefold sensory threshold (INT 1), motor plus sensory threshold (INT 2), individual level of tolerance (INT 3). STATISTICS: Multivariate analyses of variance (independent variable: stimulation intensity). RESULTS: Three negative and two positive midlatency components were identified after median nerve stimulation. At INT 1 the early waves N20, P25 and N35 were identified in all of the patients. In contrast, the component P45 was identifiable in 23% of the sample at the lowest intensity level and N55, respectively, in 32%. At INT 2 the spinal and the midlatency cortical amplitudes (except amplitude N35P45) were significantly increased (p < 0.014). At INT 3 the amplitudes of the primary cortical complex did not increase further, but the components > 35 ms became identifiable in the whole sample except in one subject. In contrast, there was no change in the MnSSER latencies. The intensity was comfortable for all subjects. CONCLUSION: For monitoring the midlatency MnSSER components > 35 ms the authors suggest a stimulation intensity close to individual tolerance level for optimal cortical responses. PMID- 11776661 TI - Motoneuron activity in patients with different types of tremor. AB - The aim of this work was to examine the segmental motoneuron activity as a possible mechanism of tremor generation. Eighty-three patients with different types of tremor (25 with Parkinsonian, 29 with essential, and 30 with enhanced physiological tremor due to anxiety), 25 Parkinsonian patients without tremor and 30 healthy volunteers were examined. The tremor was studied clinically and by electromyography in all limb positions. The F wave was examined for assessment of motoneuron activity. The wave was recorded after stimulation of the ulnar, median, tibial and fibular nerves. The maximal and mean F wave amplitudes, frequency of occurrence and number of phases were increased, and the duration was prolonged in all group of patients as compared to the healthy persons. The maximal and the mean F/M amplitude ratios, as well as the Fmean./Fmax amplitude ratio were increased in all groups of patients. All F wave parameters were most altered in Parkinsonian tremor patients followed by patients with rigidity. In conclusion increased motoneuron activity participates in generation of different types of tremor and in Parkinsonian rigidity. PMID- 11776662 TI - Time axis calibration in human CNS organization for judging dysfunction. AB - Based on measurements of relative phase and frequency coordination between the firings of neurons in the human central nervous system (CNS) with the single nerve fibre action potential recording method a coordination dynamic recording method could be developed with which it is possible to measure the coordination dynamics between arms, legs and trunk non-invasively when exercising on a special coordination dynamic therapy device. To analyze integrative functions when the human CNS is generating different coordinated movements of arms and legs, a time axis calibration is needed, which catches relevant CNS organization. Repeatedly occurring characteristic movement states are found in the pace and trot gait coordination when exercising continuously on the special coordination dynamic therapy device. CNS organization dynamics is thus projected onto the changing coordination dynamics of arm and leg movement. The collective variable for measuring the coordination dynamics of a physiologically and pathologically functioning CNS, when performing coordinated arm and leg movements with changing coordination between arms and legs including pace and trot gait coordination and all intermediate coordination, is the amplitude of variation of the frequency of turning (delta f) and of its time derivative (delta df/dt). When a volunteer exercises on the special coordination dynamic therapy and recording device, it was found that the healthy CNS can generate all possible coordinations between arms and legs with small turning frequency variation (small delta f and delta df/dt). But the lesioned CNS cannot any more generate all coordinations with small frequency variation, that means easily. Often the easy pace and trot gait coordinations can be performed by the patient with small frequency variation but not the difficult intermediate coordinations or, depending on the CNS lesion, the patient can only perform pace or trot gait coordination easily or the change from the pace to the trot gait and not from trot to pace gait coordinations can be performed easily. In the most severe cases the arrhythmicity is so large that the patient starts to stop turning or cannot turn the levers any more. Also time drifting CNS organizations can be identified with this time axis calibration; the easy coordinations appear at different coordinations with ongoing time. Improvements of the coordination dynamics and deterioration of the coordination dynamics with stress were measured in the short-term memory. It is discussed that stress deteriorates relearned CNS organization in the short-term memory apart from relearned automatisms. PMID- 11776663 TI - The optimal measurement of across elbow segment in ulnar motor conduction study. AB - There is room for considerable error in the measurement of across-elbow conduction velocity due to the different possible positions of the elbow and the difficulty in accurately measuring distance. A standardized method should be used for clinical measurement. Many advocate a fully flexed elbow position with the arm abducted at 90 degrees. When the elbow is fully flexed, skin measurement across the bent elbow is difficult with respect to defining the path, which most accurately follows the nerve. However, studies on measurement technique for across-elbow segment have not been performed to date. We have proposed a standardized technique for the measurement of conduction velocity through the elbow segment. We assumed "ideal" across-elbow segmental conduction velocity is the mean of the forearm and arm segmental conduction velocities, and established an optimal deflection point at the elbow, which best reflects the ideal conduction velocity. The optimal deflection point was located medially two thirds distance between the epicondyle and the olecranon in an arm abducted 90 degrees, fully flexed elbow position. Our data suggests that an across-elbow segment velocity lower than 57.8 m/sec, or a difference of more than 7.7 m/sec between the across-elbow and forearm segments is to be considered abnormal. The lower limit values expressed as mean-2 S.D. for absolute across-elbow segmental conduction velocity and relative velocity difference between the across-elbow segment and forearm segments at other possible deflection points of the elbow were also calculated. PMID- 11776664 TI - ['Doctor, I don't want to know that'--exploring denial in patients with lung cancer]. AB - Three patients with lung cancer, a man aged 68, a woman aged 69 and a man aged 52, denied the nature or the severity of their disease in three different ways: temporary denial to evade acute emotional shock, full-blown persistent denial, and unjustified optimism respectively. The psychological mechanism of denial may become operational in patients confronted with an overwhelming disease. A less pronounced denial of medical information provided by physicians can be recognised in many patients. It may also be noticed in how individuals or groups of people sharing the same unbearable reality face up to the facts. Denial may be helpful in (temporarily) circumventing a serious problem but when the disease is serious, it may interfere in relationships with partners, relatives and friends. Denial must be differentiated from organicity, e.g. anosognosia in cerebral damage, by patient ignorance, or by vague communication from the medical community. A direct and blunt confrontation of denial may result in adverse effects due to a defensive mechanism being aggravated. Slowly providing the patient with pieces of information whilst taking into account his or her reaction, may provide a clue for gradual conformation to the medical reality. PMID- 11776665 TI - [New developments in chemotherapy for metastasized bladder cancer]. AB - Methotrexate vinblastine doxorubicin cisplatin (MVAC) has been the golden standard in the chemotherapy of metastasized bladder cancer for more than ten years. This regimen is particularly suitable for fit patients (WHO performance status 0 or 1) with a good renal function. This leads to an overall response in 40-57% of the patients and to a complete response in 13-19%. The median survival is about 15 months. Combination chemotherapy consisting of cisplatin and gemcitabine (GC) is a valuable alternative with a comparable effectiveness, but with the advantage of clearly less toxicity (neutropenic fever, mucositis, sepsis and mortality). The extra value of adding paclitaxel to this GC combination to improve the survival of this fit group of patients is currently being investigated. The value of the combination carboplatin-gemcitabine versus carboplatin-methotrexate-vinblastine as a palliative regimen with a favourable toxicity profile for the less fit patients is also currently under investigation. PMID- 11776666 TI - [Developments in the area of hearing aids]. AB - During the past 10-15 years, several techniques have been developed and refined for the treatment of hearing impairment and deafness. The size of hearing aids has been reduced and the sound processing has become more advanced. In the next 20 years sound processing will improve substantially. Although the reduction of size will not continue, the technical possibilities of small hearing aids will improve considerably. These developments will by and large remedy the present shortcomings of hearing aids. The functionality of cochlear implants has improved considerably in recent years, mainly due to improvements in sound processing and it is in this area in particular that improvements are expected during the next 20 years. In the area of bone conducting implants considerable improvements in the apparatus and operating techniques have been made. Minor developments are expected during the next 20 years. As a result of population growth and the aging of the population, the number of hearing aid users will probably multiply in the next 20 years from 380,000 to 523,000. The number of implant users will probably increase in this period. The bulk of the total costs for hearing devices will continue to be the supply of hearing aids. PMID- 11776667 TI - [Roaming through methodology. XXXVI. Likelihood ratios and Bayes' rule]. AB - In practice, the terms 'sensitivity' and 'specificity' are often used in a different sense to that found in textbooks. Their value depends on the composition of the groups in which the test was applied. It is rarely recognised that sensitivity and specificity change during the course of a disease. The interpretation of their value appears to be difficult. The likelihood ratio combines sensitivity and specificity, and is therefore associated with the same problems. The likelihood ratio is Bayes' rule in its simplest form: how does a given probability (in this case that of a particular disease being present) change with the addition of a single new fact (i.e., the result of a diagnostic test)? The Bayesian approach is applied in various fields but rarely in clinical practice, because the prior probability of a diagnosis is difficult to quantify. Likelihood ratios are useful when studying the diagnostic process and when teaching the diagnostic thought process. They can also be applied in the statistical interpretation of clinical trial results. PMID- 11776668 TI - [From gene to disease; POU1F1- and PROP1-mutations in pituitary hormone deficiency]. AB - Multiple pituitary hormone deficiency can be caused by mutations in at least three pituitary transcription factors: POU1F1 (formerly called PIT1), PROP1 or HESX1. The role of the various pituitary transcription factors in pituitary ontogeny has been elucidated in part for the mouse. In humans, mutations in POU1F1 result in a total deficiency of growth hormone and prolactin, and a variable deficiency of TSH. Cases of mutations in PROP1 exhibit the same deficiencies, with additional deficiencies of gonadotrophins and a variable deficiency of ACTH. In the Netherlands, cases of multiple pituitary hormone deficiency are not only detected on the basis of the classical signs and symptoms of pituitary deficiency, but also by means of screening on congenital hypothyroidism with an incidence of approximately 1:20,000. PMID- 11776669 TI - [Diagnostic image (68). Retrosternal struma]. AB - A very large retrosternal struma was seen at autopsy of an 88-year-old woman who had died of metastatic colon carcinoma. PMID- 11776670 TI - [Bronchial symptoms and obstruction: recent prevalence and short-term trends (1993-1997) in adults in the Netherlands]. AB - OBJECTIVE: To determine recent prevalences of, and short-term trends in, characteristics of chronic pulmonary disease amongst adults in the Netherlands. DESIGN: Long-term cross-sectional study. METHOD: An analysis was carried out on data collected from the 'Monitoring of risk factors and health in the Netherlands' study (Dutch acronym: MORGEN) in the period 1993-1997. The study involved 9791 men and 11,712 (non-pregnant) women aged 20-59 years from three Dutch cities, Amsterdam, Doetinchem and Maastricht. A written questionnaire was used to collect data on items such as respiratory symptoms, age, educational level and smoking habits. The presence of asthma symptoms was defined as: wheezing without a cold, nocturnal attacks of breathlessness or 'had ever suffered from asthma'. The presence of chronic obstructive pulmonary disease (COPD) symptoms was defined as: chronic cough, chronic phlegm or breathlessness when walking with people of the same age. Pulmonary function (FEV1) was measured only in 1994-1997 (n = 12,347). Bronchial obstruction was defined as FEV1 < 80% of predicted. Age standardisation was performed using the age distribution of the Dutch population in 1995 as standard. Changes over time were studied using linear regression analysis. RESULTS: The age-standardised prevalence of asthma symptoms (circa 14%), COPD symptoms (circa 14%) and obstruction (circa 8%) were comparable in men and women. The prevalence of respiratory symptoms and obstruction was clearly higher in subjects with a low versus a high educational level and this trend was also observed amongst those who had never smoked. After adjustment for age, education and city, the prevalence of respiratory symptoms increased during the study period in women (beta = 0.79% per year (95%-CI: 0.27-1.32)), but not in men. The strongest increase was observed in women aged 40-49 years and in those women with a low educational level. In both men and women no increase in the prevalence of bronchial obstruction was observed. PMID- 11776671 TI - [Ambulatory laparoscopic cholecystectomy is as effective as hospitalization and from a social perspective less expensive: a randomized study]. AB - OBJECTIVE: To compare the effects and costs of an ambulatory treatment versus an overnight stay for laparoscopic cholecystectomy. DESIGN: Prospective, randomised. METHOD: In the St Antonius hospital, Nieuwegein, the Netherlands, 86 patients with symptomatic cholelithiasis without comorbidity underwent either ambulatory (AM: 42 patients: 8 men and 36 women; mean age: 48.9 years (SD: 11.9)) or overnight stay (OS: 44 patients: 10 men and 32 women; mean age: 44.9 years (SD: 11.8)) laparoscopic cholecystectomy in the period 1 November 1997-30 September 1999. The following were registered: operative time, complications, hospital stay and readmissions, as well as reported pain, nausea, activity resumption, quality of life and patient satisfaction. The cost analysis was performed from a societal and hospital perspective. RESULTS: In the OS group one laparoscopic procedure was converted to open cholecystectomy, two relaparotomies were performed due to intra abdominal haemorrhage and 1 patient had a catheter inserted due to urine retention. Two patients were readmitted, one for postoperative pancreatitis and the other for a retained bile duct stone. In the AM group one laparoscopic procedure was converted to open cholecystectomy, in 1 patient a wound abscess was treated with drainage in the outpatient clinic, in 1 patient there was peroperative stone loss without further complications and in 1 patient a catheter was placed to drain peroperative bile and blood loss. In the AM group 11 (26%) patients were kept overnight due to nausea and/or pain (n = 7) or one of the aforementioned complications (n = 4). Two patients were readmitted within 24 hours of being discharged due to abdominal pain. The average hospital stay was 3.1 (OS) versus 1.7 (AM) days. The quality of life, pain, nausea and activity resumption were comparable for both groups. Due to the difference in hospital stay, costs for the ambulatory procedure were lower. CONCLUSION: Laparoscopic cholecystectomy was successfully performed as an ambulatory surgery procedure in 69% of the patients. The quality of life, patient satisfaction and resumption of activities in both groups were comparable. The ambulatory treatment was less expensive. PMID- 11776672 TI - [Brachial plexus injury due to unhealed or wrongly healed clavicular fracture]. AB - Two men, aged 65 and 27 years, had persistent dysesthesia of digits IV and V 18 and 8 months, respectively, after conservative treatment of dislocated comminuted clavicular fractures. In both patients, the fracture was found to have healed poorly. There was pseudoarthrosis, shortening and malrotation. Following surgical decompression of the neurogenic structures by elongation and internal fixation of the clavicle, motor and sensory functions recovered completely. The incidence of clavicular fractures is high, but complications are rare. Symptom recognition and timely treatment can prevent irreversible nerve damage. PMID- 11776673 TI - [Unexplained right ventricle dilatation clarified by a cardiac contusion many years ago]. AB - In a 52-year-old man with new onset atrial fibrillation, transthoracic echocardiography showed an isolated, considerably dilated right ventricle. Frequent causes of right ventricular dilatation were ruled out. The image-forming investigation showed an isolated dilation of the ventral part of the heart, which, in combination with a blunt chest trauma 30 years previously, led to a previous cardiac contusion being suspected. In accordance with this hypothesis myocardial scintigraphy showed asymmetric hypertrophy of the right ventricular wall, which is consistent with the remodeling that occurs in response to injured cardiac tissue. After electrical cardioversion sinus rhythm was obtained; the patient remained symptom free. PMID- 11776674 TI - [Ventricular fibrillation: daily, possibly leading to embolization in an extremity]. PMID- 11776675 TI - Fetal and maternal energy metabolism during labor in relation to the available caloric substrate. AB - AIM: To discuss maternal and fetal metabolic events during labor and the possible role of glucose administration. RESULTS: The oxidative pathway covers the largest part of the energy demand of labor, although in the second stage or, in polysystolic labor, the non-oxidative pathway becomes important as well. Glucose is the main maternal energy source, but the rise in ketobodies, even during normal labor, suggests a relative shortage. In the first stage of labor, a combination of a respiratory alkalosis, and to a lesser extent, a metabolic acidosis, result in a rise in the maternal pH. In the second stage of labor, the maternal pH decreases due to an increasing metabolic acidosis. Glucose is also the main fetal energetic fuel. In fetal hypoxia, lactate is produced, which in most cases is transferred to the maternal circulation. High maternal lactate concentrations, however, may interfere with this process. Furthermore, fetal hyperglycemia may lead to an increased fetal lactate production. CONCLUSIONS: Maternal hyperglycemia, may lead to an increase in maternal and fetal lactate production resulting in metabolic acidosis. Unlike high dosage intravenous glucose administration, it is not likely that oral intake of carbohydrates leads to maternal and fetal hyperglycemia and subsequently to metabolic acidosis, but studies are rare. PMID- 11776676 TI - Incidence of meconium aspiration syndrome in term meconium-stained babies managed at birth with selective tracheal intubation. AB - The delivery room management of infants born through meconium stained amniotic fluid (MSAF) remains controversial. The aim of this prospective study was to evaluate maternal and neonatal characteristics of MSAF infants and the incidence of meconium aspiration syndrome (MAS) in routine delivery room management which reserved selective intubation for depressed/asphyxiated babies. Between October 1993 and September 1997, a consecutive sample of 3745 full-term infants was analyzed. Of these, 361 were MSAF infants. No significant difference in maternal age, parity, gestational age, sex, low 1 and 5 minute Apgar scores, metabolic acidemia, or need for endotracheal intubation was found between MSAF and non-MSAF infants. Only one of the MSAF infants (0.28%), who needed intubation, developed MAS. Identification of postterm pregnancy and prenatal asphyxia is the best prevention of MAS. PMID- 11776677 TI - Predicting preterm delivery and lowering very preterm delivery rate. AB - The chances and quality of survival depend on gestational age at birth. Why has PTD not decreased during the last decade, in spite of all the known risk factors? Perinatal data bases tend to include biomedical risk factors and are assembled and analysed retrospectively. These data should form the basis for prediction, and risk factors such as stress, anxiety, inflammation (leading to elevated CRH with its role in PTD), short cervix etc, should be added when assessed prospectively. The goal is preconception and early prediction in pregnancy. Only with the implementation of efficient intervention will we lengthen pregnancies and lower the VPTD rate. More articles about the PTD and complications of preterm births should be published in the lay press. There is no room for pessimism: if everybody involved would do just a little in the right direction, the result would be enormous. Constant auditing of interventions is necessary. The most difficult to "cure" and most likely to relapse are stress, anxiety and social factors, and discrimination in obtaining basic health care. Long forgotten lessons of compassion with pregnant women have not yet been acknowledged as proven to change VPTD into PTD, but are available at no cost world wide. PMID- 11776679 TI - Eigenvector based spatial filtering of fetal biomagnetic signals. AB - In this paper we demonstrate the usefulness of an eigenvector based spatial filtering method for signal processing of multi-channel fetal magnetocardiogram (fMCG) and fetal magnetoencephalogram (fMEG) recordings. This method of filtering can separate signal and interference by exploiting the considerable spatial information contained in multi-channel recordings. Typically, fMCGs and fMEGs suffer from large cardiac interference and low signal-to-noise ratio. To isolate the signal from the interference, we identify their respective subspaces using one portion of the record dominated by the signal and another dominated by the interference. Each subspace is approximately rank two since the sources of the signal and interference can be modeled as current dipoles. The spatial filter consists of a linear transformation that preserves the signal subspace and annihilates the interference subspace. It is easier to implement than a matched filter, preserves the morphology and topography of the fetal signal, and effectively removes maternal cardiac interference, even when the maternal and fetal complexes overlap strongly in time or when small maternal movements or maternal arrhythmias alter the temporal character of the interference. PMID- 11776678 TI - Comparative effects of chronic exposure to glucose or sodium butyrate on surfactant development in fetal rabbits. AB - BACKGROUND: Infants of diabetic mothers (IDM) often have delayed lung development and are thus at an increased risk of Respiratory Distress Syndrome (RDS). Both hyperglycemia and/or hyperinsulinemia have been implicated in this delay but the precise mechanism has not been clarified. Another metabolite, sodium butyrate, which is increased in IDM has been shown to decrease surfactant production in vitro but its effects on the development of the fetal lung surfactant system in vivo have not been studied. AIM: To investigate the in vivo effects of high glucose and sodium butyrate treatment on maternal and fetal glucose and insulin levels and on fetal lung surfactant maturation using timed-pregnant New Zealand White rabbits. METHODS: On the 24th day of gestation the doe was implanted s.c. with time release pellets containing either glucose (300 mg), sodium butyrate (200 mg) or matching placebo. On the 27th or 30th day maternal (ear vein) and fetal (cardiac puncture) blood samples were drawn for glucose and insulin determinations. Fetal surfactant pools (both intra- and extracellular) were quantitatively harvested using differential and density gradient centrifugation and their phospholipid profiles determined. Data were statistically compared with ANOVA and Duncan's Multiple Range Test. RESULTS: Neither glucose nor sodium butyrate affected maternal plasma glucose or insulin. Both metabolites significantly increased fetal plasma insulin, decreased fetal plasma glucose but did not delay any of the parameters of surfactant maturation examined. CONCLUSIONS: Fetal hyperinsulinemia, whether attained by prolonged exposure to elevated glucose or sodium butyrate in vivo does not appear to be the causative agent for delayed lung maturity which frequently occurs in infants of diabetic mothers. PMID- 11776680 TI - Localization and quantification of adhesion molecule expression in the lower uterine segment during premature labor. AB - AIMS: To investigate localization and concentration of adhesion molecules in the human lower uterine segment during preterm parturition. METHODS: In a prospective study biopsy specimens from the lower uterine segment of 43 patients undergoing cesarean section at 24 + 0 to 36 + 4 weeks' gestation were immunostained for intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1, and the concentrations measured by enzyme immunoassay. The results were analyzed in relation to the degree of cervical dilatation (< 2 cm, 2- < 4 cm, > or = 4 cm) and duration of labor (< or = 6 h, > 6-12 h; > 12 h). RESULTS: Intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule 1 were strongly expressed by capillary endothelium, endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 to only a minor degree. Intercellular adhesion molecule-1 concentration was greater at > or = 4 cm dilatation than at 2- < 4 cm and after > 12 h labor than after < or = 6 h. Endothelial leukocyte adhesion molecule-1 concentration was greater after > 12 h than after < or = 6 h. CONCLUSIONS: Premature labor is associated with up regulation of adhesion molecules in the lower uterine segment. PMID- 11776681 TI - Is intrapartum vibroacoustic stimulation an effective predictor of fetal acidosis? AB - OBJECTIVE: The hypothesis of this prospective study is that intrapartum vibroacoustic stimulation (VAS) is an effective predictor of fetal acidosis during labor. Various clinical conditions, such as term versus preterm gestation, first stage versus second stage of labor, and fetal heart rate (FHR) variable decelerations versus late decelerations will be tested. METHODS: During the study period, 113 patients were studied prospectively in either active phase of first stage (n = 53) or during the second stage of labor (n = 60). They were selected from cases exhibiting moderate to severe FHR variable decelerations or late decelerations. The fetuses of study subjects received a VAS for three seconds and FHR changes were recorded. Fetal scalp blood pH or umbilical arterial blood pH was obtained within 15 minutes of VAS. The relationship between FHR responses to VAS and fetal blood pH in term and preterm gestations, the relationship of two tests (VAS and fetal blood pH) to type of FHR decelerations, and the predictability of neonatal morbidity by two tests were analyzed. Where appropriate, Fisher's exact test (p < 0.05 was considered statistically different) and the odd ratio with 95% confidence intervals were used for statistical analyses. RESULTS: Excellent association between acceleration response to VAS and pH > or = 7.20, and between a negative response to VAS (no acceleration or decelerations) and pH < 7.20 were found in the first stage of labor, the second stage of labor, and the combination of both stages together (p = 0.0001, OR = 10.6 [3.3-34.0]). It was observed that negative VAS responses for predicting fetal acidosis (pH < 7.20) were comparable between term (> or = 37 weeks) and preterm (< 37 weeks, > or = 34 weeks) fetuses. Since the preterm fetuses enrolled in the study were limited in number, it is difficult to draw adequate conclusions. The positive predictive value (PPV) of fetal acidosis was 67% in both groups of FHR variable decelerations and late decelerations, but the false negative rate of acceleration VAS response for predicting no acidosis was significantly higher in the group of late decelerations (29% vs 8%, p = 0.034). Finally, both a negative VAS response and fetal acidosis (pH < 7.20) have equal predictability for neonatal morbidity. The PPV of NICU admission by a negative VAS response was two times higher than that of fetal acidosis (PPV = 61% vs 29%, p = 0.038). CONCLUSION: We found that intrapartum VAS was an effective predictor of fetal acidosis in cases of FHR variable decelerations, but its predictability for fetal acidosis in cases of FHR late decelerations was limited. Both VAS and fetal blood pH are good predictors of neonatal morbidity. PMID- 11776682 TI - Plasma adrenomedullin levels in pregnancies with appropriate for gestational age and small for gestational age infants. AB - AIMS: To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. METHODS: Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured. RESULTS: There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups. CONCLUSIONS: These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants. PMID- 11776683 TI - Tissue concentrations of cytokines in the lower uterine segment during preterm parturition. AB - AIMS: To determine the concentrations of tumor necrosis factor alpha, interleukin 1 beta, interleukin-6, and interleukin-8 in the lower uterine segment during preterm parturition. METHODS: In 71 patients who delivered prematurely by non elective cesarean tissue specimens were obtained from the lower uterine segment. The patients were grouped in relation to the stage of cervical dilatation (< 2 cm, 2- < 4 cm, > or = 4 cm), duration of labor (< or = 6 h, > 6-12 h; > 12 h), and parity (1 versus > 1). Cytokine concentrations in protein extracts of the tissue samples were measured using enzyme-linked immunosorbent assays. RESULTS: Median concentration of tumor necrosis factor alpha did not change, but that of interleukin-1 beta, interleukin-6, and interleukin-8 were significantly higher at 2- < 4 cm than at < 2 cm cervical dilatation (6.6, 67.7, and 125.8 versus 1.1, 17.6, and 22.2 pg/mg protein, respectively). The concentrations of interleukin-6 and interleukin-8 showed a further increase at > or = 4 cm (297.2 and 468.6 pg/mg, respectively), but for interleukin-1 beta a decrease was observed (0.6 pg/mg). Cytokine concentrations were not related to duration of labor or parity. CONCLUSIONS: Local inflammation-associated changes that are mainly related to the stage of cervical dilatation and to only a minor degree to uterine activity may play a crucial role in preterm parturition. PMID- 11776684 TI - Effect of labor on maternal dehydration, starvation, coagulation, and fibrinolysis. AB - BACKGROUND: Dehydration, starvation, and enhanced blood coagulability may occur during labor. METHODS: We studied 60 women who gave birth vaginally to a healthy singleton infant at term. Sampling of urine and blood specimens was performed on admission to the hospital with labor pains and just after birth. Paired samples were available from 50 women for urine analysis and 29 women for blood analysis. Total fluid intake (oral and intravenous) during labor was recorded. Changes in various parameters in the urine and blood in relation to the total fluid intake were analyzed. RESULTS: Osmolality and creatinine concentration in the urine, red blood cell count, hemoglobin concentration, hematocrit value, thrombin antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex and D dimer significantly increased during labor. Ketone bodies were absent in the urine in 84% (42/50) of women on admission to the hospital whereas these were present in 74% (37/50) of women just after delivery (p < 0.01). The degree of these changes appeared to be smaller with an increase in fluid intake. CONCLUSION: Concentrated urine, hemoconcentration, starvation, and activation of the thrombogenic and fibrinolytic system occur in parturient women. Sufficient fluid intake during labor may ameliorate these unfavorable changes. PMID- 11776685 TI - Changes in light-induced fluorescence of cervical collagen in guinea pigs during gestation and after sodium nitroprusside treatment. AB - Light-induced fluorescence (LIF) of collagen was used to investigate in vivo changes in cervical collagen in guinea pigs during gestation and following sodium nitroprusside treatment. Natural fluorescence of collagen is due to collagen cross-linking molecules that connect single collagen fibers and therefore provide rigidity of the cervical stroma. LIF of cervical collagen was measured from the surface of the exocervix in anesthetized nonpregnant and timed pregnant guinea pigs at different times of gestation with an instrument designed in our lab (Collascope). Measurements were also performed in guinea pigs at midgestation before and 8 hours after intracervical treatment with sodium nitroprusside. Collagen fluorescence decreased significantly as pregnancy progressed, reached lowest values at delivery, and increased gradually postpartum. Treatment with sodium nitroprusside, but not with the vehicle, caused a significant decrease in LIF (p = 0.007). We conclude, that LIF changes in the cervix reflect the gradual cervical softening (ripening) during pregnancy and the return to the rigid state of the cervix postpartum. Cervical softening during pregnancy, and after sodium nitroprusside treatment, is associated with a decrease in collagen cross-links. Measurements of LIF can be used to investigate cervical softening in vivo. PMID- 11776686 TI - Cardiotocography or Doppler in making delivery decision? PMID- 11776687 TI - [Neonatal screening for cystic fibrosis]. PMID- 11776688 TI - [Bacterial epidemiological study of acute otitis media in children observed at home in the Nord Pas-de-Calais region]. AB - BACKGROUND: The aim of this work is the study of the bacteriologic epidemiology of acute otitis media in infants observed at home in Nord Pas-de-Calais area, and the analysis of bacteria associated to recurrent otitis and clinical failure. OBSERVATIONS: A total of 295 specimens of ear pus specimens were collected from children (mean age: 18 months; average: one month-12 years). Pneumococcus strains were isolated from 52% of samples and 80% of these showed resistance to penicillin. H. influenzae was found in 35% of specimens and the half produced a beta lactamase. Pneumococcus is the predominant pathogen isolated in prolonged otitis media, while H. influenzae is preferentially found during recurrent otitis media. The main bacteriologic cause of failure traitement was penicillin intermediate or -resistant pneumococci. The therapy administered 48 to 72 hours before collection of ear pus sample in therapeutic failure was ineffective (oral cephalosporins or macrolides), or administered to low dosage (50 mg/kg/j). CONCLUSION: Our results demonstrate, in opposition to other studies, Streptococcus pneumoniae as the most frequent pathogen in acute otitis media. They also show the excellent correlation between antibiotic therapy and clinical failures. PMID- 11776689 TI - [Association between type 1 diabetes and polymorphism of the CTLA-4 gene in a Tunisian population]. AB - Susceptibility to type 1 diabetes mellitus is strongly associated with particular HLA class II alleles. However, non HLA genetic factors are likely to be required for the development of disease. The candidate genes include the cytotoxic T lymphocyte associated 4 (CTLA-4) located on chromosome 2q33 and designated (IDDM12), which encodes a cell surface negative signal T molecule providing for activation. We investigated CTLA-4 exon 1 dimorphism in 74 type 1 patients and a control group of 48 healthy subjects from Tunisia using two methods PCR (polymerase chain reaction) allele specific and polymerase chain reaction restriction fragment length polymorphism (PCR RFLP). The CTLA-4/G allele was found on 68.9% in type 1 patients as compared to 51.02% in controls (p = 0.002), mostly in homozygous from 43.24% versus 22.45% (p = 0.0058). This results indicate that CTLA-4/G allele was significantly associated with predisposition to type 1 diabetes in our group from Tunisian population. PMID- 11776690 TI - [Comparative study of the BACTEC 9000 MB system and Lowenstein Jensen media for mycobacterial culture]. AB - An automated system for mycobacteria culture, BACTEC 9000 MB, was compared with Lowenstein Jensen culture. On a total of 4,484 pulmonary and extrapulmonary human clinical samples, 126 (2.8%) were positive for mycobacteria on Lowenstein Jensen (LJ) medium; 105 (2.34%) were identified as Mycobacterium tuberculosis and 39 (1.10%) as non tuberculosis mycobacteria. The mean time of detection of Mycobacterium tuberculosis on the 131 positive samples was reduced to approximately ten days with BACTEC 9000 MB compared to the LJ (17.6 versus 27.38 days). Through the results of this comparative study, we confirmed that BACTEC 9000 MB is a more efficient system than LJ for culture detection of all mycobacteria from various sites samples. PMID- 11776691 TI - [Nodular fasciitis or pseudosarcoma]. AB - Nodular fasciitis is a benign neoplastic and reactive proliferation of fibroblasts of soft tissues, which is often mistaken for a sarcoma because of its rapid growth, rich cellularity and mitotic activity. A case is reported that provides the opportunity to discuss the specific clinical and pathological features of nodular fasciitis. PMID- 11776692 TI - Infection and/or colonization by methicillin-resistant Staphylococcus epidermidis (MRSE). AB - We analyzed the parameters predictive of identification of methicillin-resistant Staphylococcus epidermidis (MRSE) in sample performed in hospitalized patients. One hundred six Staphylococcus epidermidis strains (60 MRSE and 46 MSSE) were collected. Three variables were independently linked to MRSE isolation in multivariate analysis: hospitalization during the month preceding the current admission; on-going antimicrobial therapy before sampling, and on-going infection at the time of sampling. MRSE isolation was associated with a poor vital prognosis. The air and surfaces sampling in the rooms of two patients with nasal MRSE carriage yielded the same strains as those carried by the patient, and could play a role in the epidemiological chain of hospital-acquired MRSE infections. PMID- 11776693 TI - [Diagnosis and treatment of bladder tumors by photodynamic therapy]. AB - Experimental results and clinical trials showed that bladder tumours Tis and pT1a can be diagnosed by photodynamic diagnosis and treated by photodynamic therapy. These photochemical methods are based on a selective photosensitizer uptake in the tumour tissue. After subsequent irradiation, these tissues emit a fluorescence (diagnosis) or can be destroyed by chemically induced oxidative compounds (treatment). Hematoporphyrin derivative and its oligomeric part have been the light-sensitizing drugs the most commonly studied. Interest has now shifted to 5-aminolevulinic acid, or its hexylester form, inducing protoporphyrin IX which shows better tumour localising properties and could avoid side effects. While photodynamic treatment is still an experimental modality, photodynamic diagnosis could achieve a more accurate detection of occult dysplasia compared to white light cystoscopy. PMID- 11776694 TI - [Implication and mode of action of infectious agents in the formation of atheromatous plaques. Infection and atherosclerosis]. AB - Different kinds of infectious agents seem to be implied in the atherosclerotic process. Indeed, some bacteria and viruses have been identified in atherosclerotic lesions: Chlamydia pneumoniae, Helicobacter pylori, Streptococcus sanguis, Porphyromonas gingivalis, herpes simplex viruses type 1 and 2, coxsakievirus B and hepatitis virus A. By their ability to induce antigenic and functional changes in the cells of the vascular wall (endothelial cells, smooth muscle cells, monocytes/macrophages, and fibroblasts) and to stimulate immune response as well as oxidative stress, it is more and more tempting to speculate that infectious agents probably play key roles in the initiation and in the formation of atherosclerotic plaques in certain patients. PMID- 11776695 TI - [Cyclin dependent kinase inhibitors and replicative senescence]. AB - Replicative senescence is defined for human diploid fibroblasts in culture as a cell growth arrest appearing beyond 50 +/- 10 population doublings and associated with telomeres' shortening. This phenomenon shows an increased expression of growth cell inhibitors: p21Waf1 described as an universal CDK inhibitor and p16INK4a as a specific inhibitor for both G1 phase kinases CDK4 and CDK6. The cell proliferation inhibitor p14ARF, product of INK4a/ARF locus is involved in replicative senescence too. Overexpression or homozygotic deletion of these inhibitors demonstrated their role in senescence induction. These proteins are involved in two different metabolic pathways, the first including p53, represented by E2F, ARF, MDM2, p53, p21Waf1, and the second concerning pRb and p16INK4a. These two pathways present numerous interactions and the polymerase (PARP) in relation with p53 and activated by telomere shortening might represent via p21Waf1 a link between this shortening and cell cycle control. An another metabolic pathway involving PTEN and p27KIP1 is discussed in senescent-like phenotype induction, but its activity in replicative senescent is uncertain. PMID- 11776696 TI - [Streptococcus pneumoniae: lack of emergence of pristinamycin resistance]. AB - Since 1997, a few studies have been published suggesting the emergence of clinical isolates of Streptococcus pneumoniae resistant to pristinamycin. Such results were not confirmed by recent studies from different investigators using reference techniques for the determination of susceptibilities, which is in accordance with the low probability of emergence of resistance to this antibiotic in vitro. Discrepancies are encountered with macrolide-resistant strains and may be due to the type of method used for susceptibility testing (agar-diffusion test), the final inoculum used in this technique, or the recent lowering of breakpoint for susceptibility. On the contrary, correlation between reference techniques and commercial galleries using liquid medium is excellent. Despite 35 years of exerting selective pressure, the in vitro activity of pristinamycin remains constant against clinical isolates of S. pneumoniae. PMID- 11776697 TI - [Cornea bank of Lyon: from quality diagnosis to ISO 9001 certification]. AB - The tissue and cell bank of the HCL (Hospices Civils de Lyon) has, since 10 June 1999, consisted of two sections with related activities: cell culture for the Skin Substitutes Laboratory (Laboratoire des Substituts Cutanes, LSC) and preservation of corneas at 31 degrees C for the Cornea Bank. As the LSC had been ISO 9001 certified since March 1997 our aim, since merger, was to raise the Cornea Bank to the same level of quality as the LSC, so as to coincide with the renewal of the LSC certificate in February 2000. The methods we used (project, quality control, analysis and process optimization) led us to receive official certification only nine months after the merger. The procedure started with a program of quality control at the Cornea Bank from February 1999 onwards, in order to list the work and equipment required, evaluate its documentation system and what was needed to incorporate this new activity into the existing system of quality assurance at the LSC. On the 7th March 2000, the Tissue and Cell Bank of the HCL obtained an ISO 9001 certificate for its combined functions. As well as achieving our objectives and the strong points highlighted by the auditor during the renewal process, this quality assessment revealed many advantages: improvements in the conservation of corneas, economies in staff replacement and reductions in both the cost of maintaining quality, the cost of the corneas themselves, etc. The decree 'Banque' no. 99-741 of 30th August 1999, which put in place the system of authorization of tissue banks in France, demands quality control. Our application for certification which started in early 1999 had anticipated this regulation. This helped us enormously when compiling the dossier accompanying the official request and was an essential element in obtaining the favourable response of the ASSAPS on 21 June 2000. PMID- 11776698 TI - [Treatment of hemorrhoids. Consequences of clinical practice guidelines]. PMID- 11776699 TI - [Truth in science]. PMID- 11776700 TI - [Lead poisoning in adults. Experience of the Poison Control Center of Marseille from 1993 to 2000]. AB - OBJECTIVE: Report the experience of the Marseille's anti-poison center with lead poisoning adults. PATIENTS AND METHODS: Between 1993 and 2000, 45 adults patients consulted the poison Centre of Marseille for a history of lead exposure (9 women, 36 men, average age 44 YO, between 22 an 76 YO). The lead sources were mostly occupational (welding, heavy metal industries...), but some were environmental (shooting as a hobby, hunting,...). RESULTS: Ninety-one percent of the patients presented with a clinical feature of possible lead intoxication (asthenia, abdominal pain, anaemia, seizures,...). For 22 patients, calcitetracemate provocation test was negative. 6 patients with a positive test refused to be treated. 16 patients with a positive test were treated with chelation therapy (average lead blood level 566 micrograms/l--mini 320 micrograms/l, maxi 943 micrograms/l--and average lead urine elimination 3,011 micrograms/24 H--mini 789 micrograms/24 H, maxi 7,229 micrograms/24 H. 58 cures were done (1 to 12 cures for each patient). The average quantities of lead eliminated in the urine during the chelation therapy was 30,912 micrograms +/- 29,059 micrograms by case. For 12 patients who stopped the lead exposure after the diagnosis of lead poisoning, the chelaion therapy permitted to decrease the lead blood level of 69%. For 4 patients still exposed during the treatment, the lead blood level decrease of 7% only. For the 16 treated patiEnts, a clinical improvement was noted, and no adverse effects of chelation therapy was observed during the 58 cures. PMID- 11776701 TI - [Evaluation of changing antibiotic prescription habits in a general hospital center]. AB - OBJECTIVE: Two audits of antibiotic prescriptions were conducted within the framework of the fight against bacterial resistance conducted at the Valence Hospital Center (Drome, France). The first was made between July 1st and 31st 1998 and the second between December 15th 1999 and January 15th, 2000, both based on the prospective observation scheme. PATIENTS AND METHODS: We studied prescriptions written for antibiotics, recording the compound prescribed, the therapeutic indication, the type of infection and the prescriber. Results of these two audits were compared with the chi-square test. RESULTS: The prescriber was correctly identified (name + signature) on 63.1% of the prescriptions in 1998 and on 92.9% in 1999-2000. The patient was correctly identified (name + first name + age) in 89.9% of the prescriptions in 1998 compared with 95% in 1999-2000. For the compounds prescribed, 30.2% of the prescriptions were complete (name + dose + frequency + duration + administration route) in 1998 compared with 44.5% in 1999-2000. The antibiotic was prescribed for prophylactic purposes in 16.2% of the cases in 1998 and in 8.6% in 1999-2000. Empirical curative antibiotic therapy was prescribed in 44.7% of the cases in 1998 and in 49.3% in 1999-2000. Curative antibiotic therapy was prescribed in 16.2% in 1998 and in 9.3% in 1999-2000 for proven infection and with no mention of proof in 22.9% in 1998 and 32.8% in 2000. DISCUSSION: We observed an improvement in the identification of the prescriber, the patient and the drugs used between the two audits. These results were generally satisfactory and reflect the impact of an information campaign conducted after the first audit. Such audits are part of the ongoing policy designed around the antibiotic booklet and within the framework of the newly instituted antibiotic committees. PMID- 11776702 TI - [Clostridium difficile bacteremia]. AB - BACKGROUND: Extra-digestive manifestations of Clostridium difficile infection are very uncommon. Exceptional cases of C. difficile bacteremia or severe sepsis have been described in intensive care patients, demonstrating the capacity of this agent to generate generalized infection. CASE REPORT: C. difficile bacteremia occurred in a 66-year-old immunodepressed patient treated for acute myeloblastic leukemia. Bacteremia was associated with a abscess of the anal margin. Outcome was favorable after treatment with metronidosole. DISCUSSION: Clostridium difficile is generally selected by prior antibiotic treatment. It is the principal agent of nosocomial diarrhea. In immunodepressed patients, systemic dissemination is a rare but possible development. PMID- 11776703 TI - [Initial hypophosphatemia, the only factor associated with acute hepatocellular failure in exercise-induced malignant hyperthermia]. PMID- 11776704 TI - [Amygdalitis in Wegener's disease]. PMID- 11776705 TI - [Practice guideline recommendations for treatment of hemorrhoids]. PMID- 11776706 TI - [Current problems posed by staphylococcal infections in pediatric patients]. AB - A PEDIATRIC PATHOGEN: Staphylococci remain one of the most important pathogenic agents leading to community-acquired infection in children. Over the last decades, there has been an evolution in the localizations of these infections: dramatic pleuropulmonary staphylococcal infection in newborns has almost entirely disappeared in developed countries. Conversely, skin infections and soft tissue infections as well as bone and joint localizations are frequent. The severity of these bone and joint infections has however declined allowing less aggressive therapeutic regimens. One of the current problems is the risk of emergence of meticillin-resistant strains causing community-acquired infections. Such infections have been very rare in France but careful monitoring is nevertheless necessary. NOSOCOMIAL INFECTION: Staphylococci are however the leading cause of nosocomial infections in children, particularly in intensive care units. All localizations are concerned, especially catheter-related septicemia and pneumonia. There has been an increasing trend for Staphylococcus aureus and coagulase-negative staphylococci infections. Most of the strains isolated are meticillin-resistant. TOXINS: Staphylococcus aureus secretes toxins leading to specific diseases: enterotoxins cause food-poisoning and exofoliatines cause generalized exfoliation and bullous impetigo. Staphylococcal scarlatina is related to the shock provoked by staphylococcal toxins: TSST-1 and entrotoxins. Staphylococcal toxic shock syndrome is a relatively new entity more frequently observed in adults but which was initially described in children. The disease may develop during any staphylococcal infection, particularly after superinfection of a skin burn or varicella. MECHANISM OF ACTION OF TOXINS: Staphylococcal toxins act like superantigens, capable of provoking polyclonal activation of a large number of T cells. This leads to the release of an important quantity of cytokines that intervene in the pathogenesis of toxic diseases. This polyclonal activation has been observed in other pediatric diseases of unknown origin but in which the involvement of staphylococcal toxins can be suspected. There is solid evidence in favor of staphylococcal toxins in Kawasaki syndrome. Likewise, these toxins could be implicated in sudden death syndrome in infants and in acute exacerbations of atopic exzema. PMID- 11776707 TI - [Genetic factors in multiple sclerosis]. AB - GENERAL DATA: The clinical manifestations and neuropathological signs of multiple sclerosis have been recognized for more than one hundred years, but the cause remains unknown. EPIDEMIOLOGY: Multiple sclerosis is not evenly distributed throughout the world. There is an important north-south gradient in the northern hemisphere and inversely in the southern hemisphere; multiple sclerosis is more frequent in the higher altitudes. For a given latitude, there is a difference by ethnic origin. These observations indicate that multiple sclerosis is a multifactorial condition determined by both genetic and environmental factors. STRATEGIES OF GENETIC STUDIES: Progress in our knowledge of the human genome and statistical analysis techniques have made it possible to search for genetic factors in multiple sclerosis using two complementary approaches. The first is by anonymous screening and the second is to search for a candidate gene. The HLA locus is the only one with an identified predisposing effect for multiple sclerosis. It only accounts for 10 to 20% of the genetic predisposition for multiple sclerosis and many factors remain to be discovered. PMID- 11776708 TI - [The PROGRESS study for the prevention of recurrent cerebrovascular accident]. PMID- 11776709 TI - Choices. PMID- 11776710 TI - Reasons for failure of the ketogenic diet. AB - This study examined reasons why patients discontinue the ketogenic diet. A total of 46 children placed on the ketogenic diet between November 1994 and August 1996 were followed prospectively. Reasons for discontinuing the diet prior to 6 months were analyzed. Nineteen (41%) children discontinued the diet for either medical or nonmedical reasons. Nonmedical reasons were caregiver issues and patients' unwillingness to follow the diet. Noncompliance was more common in older children. The ketogenic diet, while effective, is a very stringent diet. Nonmedical reasons for discontinuation are as common as the traditional medical reasons of lack of efficacy or complications. PMID- 11776711 TI - Photodynamic therapy: a novel treatment for primary brain malignancy. AB - Providing therapy that conserves healthy brain tissue while effectively killing cancerous tissue remains a major challenge in the treatment of primary malignant brain tumors. The most common primary brain malignancies tend to recur despite intensive therapy, and the side effects of radiotherapy and chemotherapy can have considerable influence on health and quality of life. Photodynamic therapy (PDT) is a new technology being investigated to fulfill the need for a targeted cancer treatment that may reduce tumor recurrence and extend survival with few adverse effects. An investigational treatment, PDT employs wavelength-specific light in combination with a photosensitizing agent. The photosensitizing agent accumulates in tumor cells and is activated by nonthermal light, producing radical oxygen species that locally kill tumor cells. The selectivity of the process makes PDT appealing in the brain, where conservation of healthy tissue is vital. The most widely studied photosensitizer causes several weeks of ocular and cutaneous photosensitivity. Nursing care of the PDT patient includes intracranial pressure monitoring, neurological assessment, and intensive patient and family education. Many new photosensitizing compounds and varying methods of light delivery are being studied. This technology shows promise for the treatment of primary brain malignancies. PMID- 11776713 TI - Quality of life of stroke survivors: a research synthesis. AB - Stroke is the third leading cause of death and a major cause of disability in the United States. Individuals experiencing a completed stroke are faced with a multitude of challenges to restore their highest quality of life within the limitations of residual impairment. This research synthesis provides a summary of previous research on quality of life for stroke survivors. Research studies for inclusion in the review were identified by conducting a search of computerized databases through August 2000 and by using the ancestry method of reviewing reference lists from relevant publications. Thirty-nine studies were identified that focused on stroke survivors' quality of life during the recovery process. Stroke survivors' overall quality of life varied based on the country where the study was implemented. Variables positively associated with stroke survivors' quality of life were independence with activities of daily living, increased functional ability, social support, and healthcare resources. Variables negatively associated with stroke survivors' quality of life were psychological impairment, severity of impairment, severity of aphasia, inappropriate reactions to illness and pessimism, and inability to return to work. Specifically, 22% to 73% of the variance in stroke survivors' quality of life was primarily explained by presence of depression; functional ability, especially the upper extremities; and socialization, in particular, leisure activities. Implications for professional nursing practice to enhance stroke survivors' quality of life include encouraging independence, managing depression, and fostering interpersonal relationships. Areas for future research include longitudinal studies, rigorous psychometric assessment of quality of life instruments, and intervention studies. PMID- 11776712 TI - Evaluation of portable bladder ultrasound: accuracy and effect on nursing practice in an acute care neuroscience unit. AB - The purpose of this evaluation was to determine the accuracy of a portable ultrasound instrument in assessing bladder volume in an acute care neuroscience population and the effect of ultrasound assessment on nursing practice in an acute care neuroscience unit. In a 6-week prospective evaluation, 105 paired ultrasound measurements were performed by 45 nurses on 30 patients suspected to be retaining urine. Sixty-seven catheterizations were performed, and volumes were compared with corresponding ultrasound readings. The first ultrasound volume readings slightly underestimated the catheterized volumes, but the volumes from the first ultrasound readings and the catheterized volumes were highly correlated. Volume readings from a second ultrasound, the average of the first and second ultrasound readings, and the higher of the two ultrasound readings did not add to the ability of the ultrasound instrument to predict catheterized volumes. Patient age and gender did not change the relationship between ultrasound and catheterized volumes. The ultrasound assessment changed nursing practice in 51% of the instances; the most common change (32%) was that nurses did not catheterize the patient. The ultrasound assessment did not change nursing practice in 49% of the instances; the most common reason (41%) was that the ultrasound confirmed the need to catheterize the patient. The instrument was therefore judged to be an accurate and reliable tool that changed nursing practice in an acute care neuroscience unit. PMID- 11776714 TI - Hope in patients with spinal cord injury: a literature review related to nursing. AB - Few studies have addressed nursing of patients with spinal cord injury (SCI) related to the phenomenon of hope. Therefore, a systematic computer-based literature review to analyze the phenomenon of hope was conducted, focusing on both empirical and theoretical perspectives, to highlight the potential for further empirical studies. The review examined existing definitions of hope, theories on hope in nursing, and methodological and empirical perspectives on studies of hope in the literature. The findings showed that hope has been defined in a theoretical and general way, which has influenced empirical and theoretical research in this developing area of knowledge. These findings show that the phenomenon of hope can be generalized (the process of hoping) and particularized (the substance of hope). In addition, this analysis demonstrates that hope is a prospective phenomenon because it is future-oriented (according to the process) and has a positive essence (according to the substance). PMID- 11776715 TI - An objective review of consumer books about back pain. AB - Back pain is epidemic, and dozens of books inform the public about this disorder. The increase in "self-help" medical books has not been accompanied by objective critiques of this important literature. We conducted an objective, quantified evaluation of the comprehensiveness and quality of these books. A Books in Print search resulted in 38 books on back pain, of which 27 were found and purchased. Topics covered, organization, and emphasis were coded according to scales with excellent interrater reliability. Alternative and conventional treatments were emphasized in most books, but epidemiology, natural history, and risk factors were substantially de-emphasized, covering less than 3% of the text. This objective and validated evaluation of the consumer literature provides a format for researching patient education in other health areas. PMID- 11776716 TI - [Malignant catarrhal fever in Switzerland: 2. Evaluation of the diagnosis]. AB - Malignant catarrhal fever (MCF) is a mostly fatal lymphoproliferative disease of cattle. In 1995 a PCR based method was introduced for the detection of the ovine herpesvirus 2 (OvHV-2), which is regarded as the causative agent of the sheep associated form of the disease. This PCR can be regarded as a gold standard for the in vivo diagnosis of sheep-associated MCF in cattle (Muller-Doblies et al., 1998). This semi-nested PCR was now used as a reference test for the reassessment of diagnostic criteria in the clinical and post mortem diagnosis that could previously not be quantitated. Based on 83 suspected cases with a complete clinical record the clinical signs were weighted and grouped according to their sensitivity and specificity into lead signs indicative of MCF and frequently accompanying signs supportive for the diagnosis of MCF and general clinical signs that were less reliable for the diagnosis. Differential diagnoses are discussed, which are of particular significance due to their status as OIE list A diseases e.g. foot-and-mouth disease or rinderpest. 38 PCR confirmed cattle with MCF served for the quantitative analysis of organ lesions. For the post mortem diagnosis an essential set of organ samples is defined to permit a reliable histological diagnosis, as the gross pathology often did not give any indication for the diagnosis. These criteria should help to improve the diagnostic efficiency and to select the appropriate laboratory diagnostic procedures for MCF suspected cattle. PMID- 11776717 TI - [Short- and longterm results after surgical treatment of teat stenosis in the region of Furstenberg's rosette using theloresectoscopy: 15 cases (1999-2000)]. AB - Teat obstructions cause considerable financial loss in dairy industry. Recently, progress in teat surgery was made by the use of minimal invasive surgical instrumentation. The technique of theloresectoscopy as well as short- and long term results of this surgical intervention are presented in this study. The clinical reports of 15 dairy cows with distal teat obstructions operated with the theloresectoscope between May 1999 and January 2000 at the clinic for ruminants, Department of clinical veterinary medicine, University of Berne were reviewed. Data collected by telephone conversation with the owners included: somatic cell count and milk flow at machine milking during the lactation of surgery (lactation 1), as well as during the lactation following surgery (lactation 2). Eighty-seven percent of the owners reported normal milk flow during lactation 1 and 93% during lactation 2. Considering the fact that only 46.7% of the cows showed negative results in the California mastitis test (CMT) during lactation 1, many owners reported a high somatic cell count being a disadvantage of this surgical technique. Normal (negative) CMT results during lactation 2, however, were reported by 80% of the owners. Isolation of Staphylococcus aureus explained the high somatic cell count in 2 of 15 cases. In conclusion, theloresectoscopy is a valuable minimal invasive surgical technique that can be fully recommended for treatment of distal teat obstructions in dairy cows. PMID- 11776718 TI - [Medetomidine-butorphanol combination anesthesia in the dog]. AB - The combination of Medetomidine and Butorphanol leads to a sufficient sedation with good analgesia and is thus superior to the application of Medetomidine only. By reducing the dosage of Medetomidine, reduced cardio-respiratory side-effects are to be expected. The comparative application of the two Butorphanol preparations Torbugesic (group T) and Morphasol (group M) did not show any differences concerning effect and tolerance. No statistically significant and clinically relevant differences between the two groups were observed for any of the parameters. PMID- 11776719 TI - Surgery for ulcerative colitis: is quality of life an issue? PMID- 11776720 TI - Seroprevalence of Schistosoma mansoni in Puerto Ricans with inflammatory bowel disease. AB - BACKGROUND: The etiology of Inflammatory Bowel Diseases, Crohn's disease (CD) and ulcerative colitis (UC), is unknown. These diseases have a higher incidence in industrialized countries and their pathogenesis involves an over-reaction of the immune system. A genetic factor is believed to predispose to the development of chronic inflammation in response to an unidentified stimulus. Exposure to infections in childhood may modulate future immune responses. Parasitosis, particularly Schistosomiasis, stimulate Th2 immune responses. It has been hypothesized that the absence of these parasitic infections, as seen in economically developed countries, favors a Th1 response that may result in the clinical appearance of Crohn's disease later in life. OBJECTIVE: To determine the prevalence of Schistosoma mansoni antibodies in Puerto Ricans with Inflammatory Bowel Disease and controls. METHODS: Serum from 92 Puerto Ricans with IBD and 106 controls was screened for S. mansoni adult microsomal antigens (MAMA) using the FAST:ELISA assay. Those positive were confirmed with an enzyme-linked immunoelectrotransfer blot test. RESULTS: Seven serum samples (3 UC and 4 controls) were positive for S. mansoni antibodies. There was no significant difference between groups in gender, municipality of origin or seroprevalence of Schistosomiasis. The control group was slightly older than the IBD group. CONCLUSIONS: Our study did not demonstrate an inverse relation between Schistosomiasis and IBD. However, the decreasing prevalence of Schistosomiasis in the general population of Puerto Rico may account for this result. PMID- 11776721 TI - Profile of the inflammatory bowel disease patient with depressive disorders. AB - OBJECTIVE: To describe the demographic and clinical characteristics of patients attending the Inflammatory Bowel Disease Clinic of the University of Puerto Rico School of Medicine and determine whether these characteristics are risk factors for the development of a depressive disorder. METHOD: Sixty-seven patients attending the Inflammatory Bowel Disease Clinic of the University of Puerto Rico School of Medicine were assessed for the presence of depressive symptoms using a simple questionnaire (CES-D) and a detailed diagnostic evaluation (CIDI-DSM IV Module E). Age, gender, education, time of IBD diagnosis, duration of treatment, psychiatric history, treatment with corticosteroids, and activity of IBD were determined and correlated with the presence of depressive symptoms and depressive diagnosis. Study data was tabulated on Epi-Info 6.0 and it was analyzed using SPSS version 10. Univariate (includes means and frequencies), bivariate (t student, Kruskal Wallis and Chi-square) and multivariate analyses (logistic regression) were performed. RESULTS: Patients older than 34 years old had three times higher probability of developing a depressive disorder (p = 0.043, OR = 3.22). Patients with a psychiatric history had seven times higher probability of developing depressive disorder (p = 0.004, OR = 7). CONCLUSION: The risk factors identified with an increased probability of developing a depressive disorder were age older than 34 years and psychiatric history. PMID- 11776722 TI - Ileal pouch-anal anastomosis for ulcerative colitis: the University of Puerto Rico experience. AB - OBJECTIVE: To review the experience with ileal pouch-anal anastomosis surgery for ulcerative colitis at the University Hospital. BACKGROUND: As many as 40% of patients with ulcerative colitis (UC) and 75% with Crohn's disease (CD) require some surgery for their disease. The number of patients referred to our clinics for evaluation and management of Inflammatory Bowel Disease (IBD) has risen in the past seven years. A multidisciplinary IBD service has been created at the University Hospital for the care of these patients, leading to a dramatic increase in the number of surgeries performed for IBD. Over the past decade the ileal pouch-anal anastomosis (IPAA) has emerged as the procedure of choice in most patients with ulcerative colitis requiring total colectomy for management of their disease. Even though the procedure is associated with a considerable morbidity rate, it has become very popular since it avoids the need for a permanent stoma and presumably rids the patient of disease and subsequent cancer risk. RESULTS: Twenty-five patients were identified as having IPAA for ulcerative colitis between 1993-2000. Indications for surgery were intractability and toxic megacolon. Complications were pouchitis in 11/25 (44%), anastomotic stricture in 6/25 (24%), small bowel obstruction in 4/25 (16%), and pouch failure in 2/25 (8%). Other complications included wound abscess in 1/25 (4%), and sexual dysfunction in 1/25 (4%) patients. There was no mortality; the patients' quality of life was rated as greatly improved in 14 of 17 patients interviewed (82.4%) and 16 of 17 said they would recommend the surgery to others (94.1%). CONCLUSIONS: The results of IPAA surgery, morbidity, mortality, and patient satisfaction in our series were similar to other centers around the world. PMID- 11776723 TI - Treatment of tropical sprue: the work of Dr. Bailey K. Ashford examined in retrospect. AB - Tropical sprue is a malabsorption syndrome that responds to treatment with folic acid and a broad-spectrum antibiotic. Eighty years ago, prior to the identification of the vitamins and the discovery of penicillin, clinical trials often consisted of best guess treatments based upon current knowledge and available technology. Dietary interventions were emerging as effective treatments for alleviation of diseases such as pellagra and beri beri. Representative of his generation of clinicians, Bailey K. Ashford, MD, one of the pivotal figures in academic medicine in Puerto Rico, carried out dietary studies in his patients with tropical sprue. This historical retrospective presents an examination of the diets used by Ashford in terms of nutrient content and comparison to current recommended dietary allowances. Results show the diets to be inadequate for sustained nutrient value and especially low in folic acid. In summary, Ashford recognized the basic causes of tropical sprue but was unable to effectively treat the syndrome due to lack of adequate resources. PMID- 11776724 TI - Immediate transfusion reactions. AB - Immediate transfusion reactions were characterized in recipients of 15,990 RBCs, 18,013 platelets, 409 single donor platelets, 3,451 FFP and 1,507 units of cryoprecipitate. The overall incidence of immediate reactions was 0.2%. Allergic reactions occurred in 40 patients, febrile non-hemolytic in 36 patients, bacterial contamination in 2 patients, circulatory overload in 3 patients and mechanical hemolysis in one patient. Three patients had nonspecific reactions. The incidence of immediate transfusion reactions was low when compared with similar studies. Possible causes are under-reporting transfusion reactions and the use of leukoreduced components. PMID- 11776725 TI - Effect of low temperature on tracheal smooth muscle contractile and relaxing responses evoked by electrical field stimulation. AB - OBJECTIVE: The aim of this work was to evaluate the effect of low temperature (LT) on the contractile and relaxing responses of rat tracheas (RTs) after electrical field stimulation (EFS). METHODS: Voltage-dependent (10-60 V, 40 Hz) and frequency-dependent (0.1-60 Hz, 40 V) response curves were constructed at 37 and 18 degrees C after the activation of tracheal intramural nerves with a Grass S88 stimulator. The EFS that produced half of the maximum contractile response (ES50) at 37 or 18 degrees C was determined and considered as the dependent variable. The % relaxation of pre-contracted RTs (EFS; 5 Hz, 40 V) to sodium nitroprusside (SNP; 1 x 10(-7) - 1 x 10(-3) M) isoproterenol (ISP; 1 x 10(-9) - 1 x 10(-5) M) and to 20 mM potassium chloride (KCl) after low-K+ inhibition of the Na+/K+ pump at 18 and 37 degrees C were determined. RESULTS: We found that the tracheal responses elicited by EFS at 37 and 18 degrees C were completely blocked with 1 microM atropine. LT slightly increases the voltage-dependent ES50, from 33.7 +/- 4.0 to 37.8 +/- 4.8 V, n = 5 but decreases the frequency-dependent ES50 from 19.3 +/- 4.3 to 1.0 +/- 0.28 Hz, n = 5, p < 0.05. Relaxing responses to SNP, ISP and KCl at 37 degrees C correspond to 43.5 +/- 6, 36.7 +/- 12 and 12.1 +/- 1.5% respectively. No significant tracheal relaxations were elicited at 18 degrees C. Our results indicate that in RTs, LT enhances tracheal sensitivity to EFS and decreases it in response to bronchorelaxants. The LT-dependent enhanced contractile response is observed only after a low frequency stimulation range (0.1-20 Hz), that is very close to the frequency of vagal stimuli required for inducing bronchoconstriction in vivo. Furthermore, LT abolishes the sensitivity of RTs to exogenously added bronchorelaxants (NO and ISP). In addition, LT appears to decrease the Na(+)-K+ pump activity; this effect has been associated with increased tracheal hyperreactivity in vitro. ACH appears to be the main endogenous neurotransmitter involved on neurally mediated contractile responses at 37 and 18 degrees C. CONCLUSION: Low temperature enhances the contractile response of rat tracheas in response to endogenous ACH release. The effect of LT is limited to frequencies below 20 Hz, which are within the physiological range required for bronchoconstriction. Furthermore, LT severely impairs the sensitivity of RTs to relaxant stimuli, either of endogenous of exogenous origin. PMID- 11776726 TI - Care for children with special health care needs in a managed care system: a patient satisfaction survey. AB - In 1994 the government of Puerto Rico adopted a capitated managed health care system for the medically indigent. The new law has been implemented in most municipalities. A survey of children with special health care needs treated at a tertiary pediatric center under the capitated managed care system and the prior non-capitated system was analyzed using the Consumer Assessments of Health Plan Survey (CHAPS) instrument. One third of the patients who were under the new capitated managed care system were not satisfied with the medial care they were receiving. The parents of children with multidisciplinary conditions found it much more difficult to access care at the tertiary center. It took parents two years to learn to navigate within the capitated managed care system. Studies to measure outcome and health quality of children with special health care needs in capitated managed health care programs must be developed to learn how the potential benefits of managed care can be maximized and the potential harms minimized. The purpose of this study was to analyze the accessibility and satisfaction of caretakers of children with special health care needs under a capitated managed health care system. PMID- 11776727 TI - Legionnaires' disease: a rare entity in Puerto Rico? AB - Legionnaires' disease is a severe, often fatal pneumonia, caused by Legionella pneumophila. Its incidence is reported about 6%. In Puerto Rico, there is no data available of the prevalence of Legionnaires' disease. A case of Legionnaires' is presented as well as data to support that the prevalence in our Island is higher than the reported elsewhere. PMID- 11776728 TI - [Memories]. PMID- 11776729 TI - [Aspects related to drug adherence in a group of caregivers of children and adolescents with epilepsy]. AB - The purpose of this study was to describe the aspects related with the adherence of medicine in patients with epilepsy diagnosis. The non probabilistic sample was composed by fifty-four parents or legal guardians of children/adolescents with epilepsy. A self-report instrument was utilized in this study and the design was based on Health Belief Model. Descriptive statistics were utilized (mean, median, frequencies and percents) to describe the results and crosstabs tables to describe specific relations between variables. It was found that the parents/legal guardians reported that they administered their children's medications as prescribed. However, the two aspects that most affect the adherence with the treatment were that the participant forgot the medicine administration and the time between each medical appointment. We conclude that the adherence problem is complex and involved a lot of individual, social, psychological, structural, attitudes, beliefs, type of medical services factors, among others. These factors will be studied more emphatically in futures studies. PMID- 11776730 TI - [Knowledge about sexuality and sex behavior in university students with visual impairment: need of educational materials]. AB - The objective of this study was to identify the knowledge about sexuality (including STD/HIV/AIDS), the sexual practices more frequents and sexuality education sources in a group of students with visual impairments. A self administered questionnaire was utilized in 50 students with visual impairment. Descriptive statistics were utilized. Seventy six percent (76.0%) of the participants presented a high knowledge about sexuality and 22.0% presented moderated knowledge. The no penetrative sexual practice more frequent was corporal caress (82.0%) and the penetrative was penis-vagina (74.0%). The source of sexuality education most common was the conferences (83.9%). Although, in general, the knowledge about sexuality was high, there are "gaps" in them. There is the need to develop educational materials adapted to the needs of the studied population. PMID- 11776731 TI - [Casuistic-inductive approximation to bioethics]. PMID- 11776732 TI - Intelligent data analysis--special issue. PMID- 11776733 TI - Classifying vertical facial deformity using supervised and unsupervised learning. AB - OBJECTIVES: To evaluate the potential for machine learning techniques to identify objective criteria for classifying vertical facial deformity. METHODS: 19 parameters were determined from 131 lateral skull radiographs. Classifications were induced from raw data with simple visualisation, C5.0 and Kohonen feature maps; and using a Point Distribution Model (PDM) of shape templates comprising points taken from digitised radiographs. RESULTS: The induced decision trees enable a direct comparison of clinicians' idiosyncrasies in classification. Unsupervised algorithms induce models that are potentially more objective, but their blackbox nature makes them unsuitable for clinical application. The PDM methodology gives dramatic visualisations of two modes separating horizontal and vertical facial growth. Kohonen feature maps favour one clinician and PDM the other. Clinical response suggests that while Clinician 1 places greater weight on 5 of 6 parameters, Clinician 2 relies on more parameters that capture facial shape. CONCLUSIONS: While machine learning and statistical analyses classify subjects for vertical facial height, they have limited application in their present form. The supervised learning algorithm C5.0 is effective for generating rules for individual clinicians but its inherent bias invalidates its use for objective classification of facial form for research purposes. On the other hand, promising results from unsupervised strategies (especially the PDM) suggest a potential use for objective classification and further identification and analysis of ambiguous cases. At present, such methodologies may be unsuitable for clinical application because of the invisibility of their underlying processes. Further study is required with additional patient data and a wider group of clinicians. PMID- 11776734 TI - Discussing anomalous situations using decision trees: a head injury case study. AB - OBJECTIVES: Predicting the outcome of seriously ill patients is a challenging problem for clinicians. METHODS: One alternative to clinical trials is to analyse existing patient data in an attempt to predict the several outcomes, and to suggest therapies. In this paper we use decision tree techniques to predict the outcome of head injury patients. The work is based on patient data from the Edinburgh Royal Infirmary which contains both background (demographic) data and temporal (physiological) data. RESULTS: The focus of this paper is the discussion of the anomalous cases in the decision trees with the domain experts (the clinicians). CONCLUSIONS: These analyses led to the detection of several situations where both the data analysis and patient data collection should be enhanced, which in turn should lead to improved patient care. PMID- 11776735 TI - Acceptance of rules generated by machine learning among medical experts. AB - OBJECTIVES: The aim was to evaluate the potential for monotonicity constraints to bias machine learning systems to learn rules that were both accurate and meaningful. METHODS: Two data sets, taken from problems as diverse as screening for dementia and assessing the risk of mental retardation, were collected and a rule learning system, with and without monotonicity constraints, was run on each. The rules were shown to experts, who were asked how willing they would be to use such rules in practice. The accuracy of the rules was also evaluated. RESULTS: Rules learned with monotonicity constraints were at least as accurate as rules learned without such constraints. Experts were, on average, more willing to use the rules learned with the monotonicity constraints. CONCLUSIONS: The analysis of medical databases has the potential of improving patient outcomes and/or lowering the cost of health care delivery. Various techniques, from statistics, pattern recognition, machine learning, and neural networks, have been proposed to "mine" this data by uncovering patterns that may be used to guide decision making. This study suggests cognitive factors make learned models coherent and, therefore, credible to experts. One factor that influences the acceptance of learned models is consistency with existing medical knowledge. PMID- 11776736 TI - Recurrent neural networks for predicting outcomes after liver transplantation: representing temporal sequence of clinical observations. AB - OBJECTIVES: This paper investigates a version of recurrent neural network with the backpropagation through time (BPTT) algorithm for predicting liver transplant graft failure based on a time series sequence of clinical observations. The objective is to improve upon the current approaches to liver transplant outcome prediction by developing a more complete model that takes into account not only the preoperative risk assessment, but also the early postoperative history. METHODS: A 6-fold cross-validation procedure was used to measure the performance of the networks. The data set was divided into a learning set and a test set by maintaining the same proportion of positive and negative cases in the original set. The effects of network complexity on overfitting were investigated by constructing two types of networks with different numbers of hidden units. For each type of network, 10 individual networks were trained on the learning set and used to form a committee. The performance of the networks was measured exhaustively with respect to both the entire training and test sets. RESULTS: The networks were capable of learning the time series problem and achieved good performances of 90% correct classification on the learning set and 78% on the test set. The prediction accuracy increases as more information becomes progressively available after the operation with the daily improvement of 10% on the learning set and 5% on the test set. CONCLUSIONS: Recurrent neural networks trained with BPTT algorithm are capable of learning to represent temporal behavior of the time series prediction task. This model is an improvement upon the current model that does not take into account postoperative temporal information. PMID- 11776737 TI - Induction of hypotheses concerning hip arthroplasty: a modified methodology for medical research. AB - OBJECTIVES: The objective of this study is to advocate a methodology for medical research that, in contrast to traditional medical methodology, exploits the flexibility of machine learning and retains the kind of statistical tests that are generally accepted in the medical field for the confirmation of hypotheses. METHODS: First, the medical problem is defined and data for an observed population are collected; then a machine learning tool is used to generate hypotheses regarding the problem; finally, statistical methods are used to determine the validity of the generated hypotheses. RESULTS: To illustrate this approach, the problem of defining indications for hip arthroplasty after an acute medial femoral neck fracture is investigated as a case study. CONCLUSIONS: The methodology is similar to the usual style of applying machine learning, but insists on a link to the techniques of statistical tests that are normally used in medicine. It aims at a more flexible and economical use of experimental data than in the usual medical research, which is enabled by techniques of machine learning. At the same time, by reference to traditional statistical tests, it is hoped that this approach will lead to improved acceptance of machine learning in the medical field. PMID- 11776738 TI - Knowledge-based and data-driven models in arrhythmia fuzzy classification. AB - OBJECTIVES: Fuzzy rules automatically derived from a set of training examples quite often produce better classification results than fuzzy rules translated from medical knowledge. This study aims to investigate the difference in domain representation between a knowledge-based and a data-driven fuzzy system applied to an electrocardiography classification problem. METHODS: For a three-class electrocardiographic arrhythmia classification task a set of fifteen fuzzy rules is derived from medical expertise on the basis of twelve electrocardiographic measures. A second set of fuzzy rules is automatically constructed on thirty-nine MIT-BIH database's records. The performances of the two classifiers on thirteen different records are comparable and up to a certain extent complementary. The two fuzzy models are then analyzed, by using the concept of information gain to estimate the impact of each ECG measure on each fuzzy decision process. RESULTS: Both systems rely on the beat prematurity degree and the QRS complex width and neglect the P wave existence and the ST segment features. The PR interval is not well characterized across the fuzzy medical rules while it plays an important role in the data-driven fuzzy system. The T wave area shows a higher information gain in the knowledge based decision process, and is not very much exploited by the data-driven system. CONCLUSIONS: The main difference between a human designed and a data driven ECG arrhythmia classifier is found about the PR interval and the T wave. PMID- 11776739 TI - Prediction in medicine by integrating regression trees into regression analysis with optimal scaling. AB - OBJECTIVES: A new data-analysis strategy is proposed to solve the problems of selecting interaction terms in linear regression on the one hand, and of statistically testing the significance of regression trees on the other hand. METHODS: The proposed strategy combines two data mining techniques: regression trees and regression analysis with optimal scaling (CATREG). The method traces small regression trees using the bootstrap and integrates the results as interaction variables (called "trunk variables") into CATREG. RESULTS: An application to data from cardiac patients shows a relative increase of 19% variance accounted for (16% cross-validated variance), by the CATREG model including the trunk variables compared to the model excluding these variables. CONCLUSIONS: This study indicates that trunk variables can be useful to model interaction effects in prediction problems. PMID- 11776740 TI - Acquisition and analysis of repeating patterns in time-oriented clinical data. AB - OBJECTIVES: (1) Creation of an expressive language for specification of temporal patterns in clinical domains, (2) Development of a graphical knowledge acquisition tool allowing expert physicians to define meaningful domain-specific patterns, (3) Implementation of an interpreter capable of detecting such patterns in clinical databases, and (4) Evaluation of the tools in the domains of diabetes and oncology. METHODS: We describe a constraint-based language, named CAPSUL, for specification of temporal patterns. We implemented a knowledge-acquisition tool and a temporal-pattern interpreter within Resume, a larger temporal-abstraction architecture. We evaluated the knowledge-acquisition process with the help of domain experts. In collaboration with the Rush Presbyterian/St. Luke's Medical Center, we analyzed data of bone-marrow transplantation patients. The expert compared the detected patterns to a manual inspection of the data, with the help of an experimental information-visualization tool we are developing in a related project. RESULTS: The CAPSUL language was expressive enough during the knowledge acquisition process to capture almost all of the patterns that the experts found useful. The patterns detected in the data by the pattern interpreter were all verified as correct. Completeness (whether all correct patterns were found) was difficult to assess, due to the size of the database. CONCLUSIONS: The CAPSUL language enables medical experts to express temporal patterns involving multiple levels of abstraction of clinical data. The ability to reuse both domain-patterns and abstract constraints seems highly useful. The Resume interpreter, augmented by the CAPSUL semantics, finds the complex patterns within a clinical time oriented database in a sound fashion. PMID- 11776741 TI - Support for fast comprehension of ICU data: visualization using metaphor graphics. AB - OBJECTIVES: The time-oriented analysis of electronic patient records on (neonatal) intensive care units is a tedious and time-consuming task. Graphic data visualization should make it easier for physicians to assess the overall situation of a patient and to recognize essential changes over time. METHODS: Metaphor graphics are used to sketch the most relevant parameters for characterizing a patient's situation. By repetition of the graphic object in 24 frames the situation of the ICU patient is presented in one display, usually summarizing the last 24 h. RESULTS: VIE-VISU is a data visualization system which uses multiples to present the change in the patient's status over time in graphic form. Each multiple is a highly structured metaphor graphic object. Each object visualizes important ICU parameters from circulation, ventilation, and fluid balance. CONCLUSION: The design using multiples promotes a focus on stability and change. A stable patient is recognizable at first sight, continuous improvement or worsening condition are easy to analyze, drastic changes in the patient's situation get the viewers attention immediately. PMID- 11776742 TI - Careless abandonment of osteopathic identity or lack of instillation in medical school? PMID- 11776743 TI - Can an Internet-based system assist with administration and distance learning for third- and fourth-year rural clinical rotations? AB - This article describes the experience of the West Virginia School of Osteopathic Medicine during the past 5 years in using Internet technology to communicate with osteopathic medical students on remote, community-based clinical rotations. Federal funding initially supported creation of a new Internet-based system to connect students on their rural family medicine rotations. Accomplishments during and after federal funding include development of systems for remote submission and student access to feedback about clinical sites; on-line access to rotation objectives, policies, housing information, maps, and affiliated internship opportunities; access to medical journals and texts; secured access to rotation grades and rotation schedules; on-line reading lists for family medicine and pediatrics rotations; and Internet-based test administration. Remaining challenges include identification or development of interactive learning materials; development of test banks; flawless administration of Web-based examinations; and finding the right balance between patient care-based learning and didactics. PMID- 11776744 TI - The ups and downs of medical school applicants. AB - The number of students applying to medical schools is shrinking after rising steadily during the 1990s. The decline is the latest turn in the behavior of the applicant pool, which historically has gone through many cycles. Although government policies have strongly influenced the past behavior of the applicant pool, the more recent cycles appear to be related to changes in the Medical College Admission Test (MCAT) and labor market conditions. This article first reviews the cyclical nature of the pool and outlines some of the important factors that have influenced its patterns. Then it focuses on more recent data covering 1990-2000, showing how changes made in 1991 to the MCAT have affected the applicant pool. Data are presented to document the close relationship between the number of students taking the MCAT and the number of medical school applicants in subsequent years. Using this relationship, a projection model has been developed for making projections of the number of applicants for the entering class in osteopathic medical schools in future years. Actual data are compared to the model's projections. PMID- 11776745 TI - A framework for and case study of medical informatics development at Michigan State University College of Osteopathic Medicine. PMID- 11776746 TI - Twelve tips for technologic transformation: the NYCOM experience. PMID- 11776747 TI - Ohio Osteopathic Network of Excellence: establishing a statewide telehealth consortium. PMID- 11776748 TI - Association between contaminant tissue residues and effects in aquatic organisms. AB - Associations between tissue residues and toxicity to aquatic organisms were examined to evaluate the applicability of the critical body residue (CBR) approach across different chemical classes. Chemical classes and mode of action categories evaluated included narcotics (polar and nonpolar), excitatory agents, AChE inhibitors, reactives/irritants, CNS seizure agents, aryl hydrocarbon (Ah) receptor agonists, and inorganic metals and organometals. This evaluation indicated that empirical data do not support broad application of the CBR concept across chemical classes. This conclusion is particularly important for polar and nonpolar narcotics because the CBR concept was specifically developed for these chemical classes. The variability observed in tissue residues between chemicals within a given mode-of-action class appears to be generally of the same order of magnitude as the variability of aqueous measures of toxicity such as LC50 values (Table 3; Fig. 10). This observation suggests that either (a) the reported tissue residues were dependent on the aqueous dosing regime; (b) the tissue measurements do not accurately reflect the internal dose at target organs with substantially greater precision than water exposure measurements; or (c) many of the same sources of variability associated with aqueous exposures, such as chemical structure, individual species sensitivity, biotransformation processes, and lipid content, also apply to tissue-based measures of exposure. An additional source of uncertainty of CBRs is whether a chemical has been correctly assigned to a mode of action category. [figure: see text] The CBR approach outlined by McCarty (1986, 1987) and McCarty et al. (1993) underlines an important concept in aquatic toxicology, i.e., that internal chemical dose is the true measure of toxicity for many chemicals rather than imputed dose based on aqueous exposure. Nevertheless, without more refined and accurate examination of that actual internal dose and without additional consideration of differences in sensitivity between species, differences in toxic potency between chemicals, and differences in toxicity of environmentally modified or biotransformed compounds, the CBR approach may not offer practical advantages over conventional media-based exposure assessment. PMID- 11776749 TI - RMS Titanic and the emergence of new concepts on consortial nature of microbial events. AB - The RMS Titanic sank in 1912 and created a historical event that still ripples through time. Stories were told and lessons learned but the science has only just begun. Today the fading remains of the ship resemble the hanging gardens of Babylon except that it is not plants that drape the walls but complex microbial growths called rusticles. These organisms have been found to be not a species, like plants and animals, but to be structures created by complex communities of bacterial species. Like the discovery of tube worms in the mid-oceanic vents, the nature of these rusticles presents another biological discovery of a fundamental nature. Essentially these microbial consortia on the RMS Titanic have generated structures of a mass that would rival whales and elephants while gradually extracting the iron from the steel. Rusticle-like consortia appear to play many roles within the environment, and it is perhaps the RMS Titanic that is showing that there is a new way to understand the form, function, and nature of microorganisms. This understanding would develop by considering the bacteria not as individual species functioning independently but as consortia of species functioning in community structures within a common habitat. This concept, if adopted, would change dramatically the manner in which a microbial ecologist and any scientist or engineer would view the occurrence of a slime, encrustation, biocolloid, rust flake, iron pan, salt deposit, and perhaps even some of the diseases that remain unexplained as a disease of unknown cause. PMID- 11776750 TI - Toxicity of azaarenes. AB - Heterocyclic compounds by far outnumber the homocyclic PAHs. In addition, they are often more soluble in water, which may imply a greater biological significance of these heterocycles. Yet, most research focuses on the homocyclics, based on the implicit assumption that the mostly higher concentration of the homocyclics rank these compounds as priority compounds. This review critically examines the available evidence and poses questions on the biological activity and environmental risk of one small group of heterocyclics, the azaarenes, which contain one nitrogen atom in one of the aromatic rings. In different sections, the biotransformation and different types of toxicity are discussed in comparison to those of homocyclic PAHs. The last section focuses on the implications for risk assessment of PAHs. Two- and three-ringed azaarenes can be relatively easily transformed by bacteria, fungi, invertebrates, and vertebrates. The presence of the N-moiety in the smaller azaarenes leads to metabolic routes that partly differ from those of the homoaromatic analogues. Major metabolic products of the azaarenes appear to be ketones and mono- or dihydroxylated azaarenes. Microorganisms can further degrade these into multiple oxygen-containing compounds or they can open up the aza-containing aromatic ring and fully metabolize the products. Fungi and vertebrates were shown to produce the mutagenic dihydrodiol metabolites. The metabolism of the larger azaarenes in vertebrates proceeds analogous to homoaromatic PAH, because in these larger molecules the N-moiety has less influence. Transformation of the larger azaarenes by microorganisms proceeds much slower if occurring at all. Direct toxicity data of azaarenes are mostly restricted to the effects of acridine and quinoline on a relatively small number of species. From this limited set it becomes clear that differences between species are relatively small. As with homocyclic PAHs, toxicity generally increases with increasing number of rings, and baseline toxicity models based on homocyclic PAHs do apply. Toxicity differences between isomers indicate that azaarene toxicity cannot be explained by molecular size related parameters alone, indicating that electronic forces may be important as well. Considering chronic toxicity it becomes clear that the often-used acute-to chronic-ratios often underestimate specific chronic toxicity, even within the very limited set of chronic data available. In contrast with homocyclic PAHs, photodegradation of azaarenes shows the same degradation products as biological transformation involving monooxygenases. In general, as for homocyclic PAHs, the degree of phototoxicity is related to the UV absorption characteristics of the azaarenes, which makes it possible to apply the QSAR models developed for homocyclic PAHs to azaarenes as well. Recent research on algae showed that UV-A is the main cause of photoenhanced toxicity. Together with the fact that in the water column UV-B is almost absent, this clearly demonstrates the relevance of phototoxicity in the field. Mutagenicity of azaarenes generally proceeds through similar pathways as in homocyclic PAHs, with bay region diol epoxides as major genotoxic metabolites. The N-moiety can, however, result in differences in genotoxic activities between isomers. Carcinogenicity of azaarenes in mammals is generally restricted to four-ringed and larger structures, and mechanisms leading to cancer are similar to those of homocyclic aromatics. An exception to this general pattern is quinoline, which has been shown to induce liver cancer. The present risk assessment for PAHs is solely based on homocyclic PAHs. Yet, from the present review it becomes clear that this approach fails to protect against a vast number of heterocyclic compounds and biotransformation products that may exhibit stronger or other toxic effects than their homocyclic analogues. Therefore, incorporating the role of heterocyclic compounds and their metabolism appears to be a necessity for a reliable risk assessment for polycyclic aromatic compounds. In addition, reliable long-term protection against PAHs demands data on chronic toxicity, including teratogenicity, both for homocyclic as for heterocyclic compounds. PMID- 11776751 TI - Enantiomeric enrichment of chiral pesticides in the environment. AB - Enantiomer fractions (EFs) of chiral compounds have been used to explain the mechanisms of enantiomer enrichment in air, soil, water, and biota. The EFs were calculated from enantiomeric ratios (ERs) of chiral compounds measured by researchers during the past 10 years. Six compounds were selected from different abiotic and biotic compartments: alpha-hexachlorocyclohexane (alpha-HCH), mecoprop, cis-chlordane (CC), trans-chlordane (TC), heptachlor exo-epoxide (HEPX), and oxychlordane (OXY). The EF was used as a general descriptor for enantiomer enrichment. In environmental compartments the EFs of chiral pesticides deviated from those of the racemic composition (EF = 0.5). The deviations from EF = 0.5 in the different compartments show similar patterns for several compounds, i.e., air < water < soil < biota. In biota the order was lower trophic level < higher trophic level and liver or kidney tissue < brain tissue. Explanations for stereoselective behavior were found in pharmacology and brain research. The enantiomeric enrichments in environmental compartments were visualized in a general scheme applicable to other persistent chiral compounds. The mechanisms of enantiomer enrichment were conceptualized by a hypothetical model of a chiral machine (enzymatic degradation) and a chiral guard (stereospecific efflux). Environmental regulation authorities should treat chiral pesticides as a composition of enantiomers because biotic processes handle enantiomers as separate chemical entities. PMID- 11776752 TI - Sentinel lymph node biopsy for breast cancer. AB - Sentinel lymph node biopsy (SLNB) is an emerging surgical technique to improve lymph node staging for breast cancer. Despite the rapid development of this technique, there remain aspects of SLNB that need to be further defined to provide a standardized approach. Variables, including patient selection, technical details for the performance of SLNB, extent of pathologic evaluation of the sentinel lymph node, and the impact of micrometastases, are areas of controversy. This paper reviews the controversies and discusses available data as well as personal experience and opinion. PMID- 11776753 TI - Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. AB - Since vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis, we determined whether blockage of VEGF receptor signaling using a novel tyrosine kinase inhibitor (PTK 787) decreases the growth and metastasis of human pancreatic carcinoma growing orthotopically in nude mice. Human pancreatic L3.6pl cells were injected into the pancreas of nude mice. Seven days later, groups of mice were given daily oral administrations of PTK 787 alone, twice weekly i.p. injections of gemcitabine, or combination therapy. The mice were necropsied when control mice became moribund (day 35). Therapy with PTK 787 alone, gemcitabine alone, or the combination of both agents produced respectively 60%, 70%, and 81% inhibition in the volume of pancreatic cancers. The combination therapy significantly decreased the incidence of lymph node and liver metastasis, leading to a significant increase in survival. Microvessel density (MVD) was significantly decreased in tumors treated with either PTK 787 alone or PTK 787 plus gemcitabine. MVD directly correlated with tumor cell proliferation and inversely correlated with apoptosis of tumor cells and associated endothelial cells. Collectively, our results demonstrate that blockade of VEGF-R signaling may provide an additional approach to the therapy of pancreatic cancer. PMID- 11776754 TI - Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma. AB - An 131I labeled trivalent antigen binding construct, formed from 3 Fab' fragments of murine anti-CEA monoclonal antibody (Mab) 35, has shown favorable biokinetics in animal studies. OBJECTIVES: The aim of this study was to evaluate biodistribution and tumor uptake of 131I-F(ab')3 in patients and its potential utility for radioimmunotherapy of CEA expressing tumors. PATIENTS AND METHODS: Six patients (5 M, 1 F; age 62 +/- 13 y) with liver metastases of colorectal cancer, scheduled for hepatic surgery were studied by 2-3 whole body scans immediately post infusion of 111-137 MBq of 131I labeled Mab 35 F(ab')3 and up to 72 h. Circulating CEA ranged from 1.2 to 1930 ng/ml. We evaluated plasma and whole body clearance, activity accumulation by post-surgical ex-vivo tissue measurement in primary tumor (T) and metastases (M), and calculated M to blood (M/B) and M to liver (M/L) ratios. RESULTS: All known tumor sites were detected by immunoscintigraphy and confirmed at surgery. Whole body effective T1/2 calculated in two patients was 51.5 h and 55.6 h respectively. Effective serum T1/2 was mono-exponential in 3 patients (short observation interval) with 20.9 +/ 7 h and bi-exponential in three with alpha T1/2 of 6.3 +/- 1 h and beta T1/2 of 38.6 +/- 5 h. In a patient with concomitant colic and hepatic lesions uptake of primary tumor was 0.0071% injected dose per gram of tissue (%ID/g) and mean metastases activity was 0.0275 %ID/g at 48 h. In the 3 patients who had surgery at 48 h, mean uptake in metastases and normal liver was 0.0182 %ID/g and 0.0021 %ID/g, respectively (M/L 8.67). In the single subject followed until 7 days post infusion, residual activity in liver metastases was 10 times higher than in normal parenchyma. CONCLUSIONS: Tumor uptake and tumor to blood ratio, as well as serum clearance of the triconstruct are similar to those observed with intact iodinated anti-CEA antibodies. In the patient studied for 7 days the tumor residence time was favorable. Further improvements, however, need to be obtained before considering this approach for radioimmunotherapy. PMID- 11776755 TI - Characterization of human tumor-infiltrating lymphocytes expanded in hollow-fiber bioreactors for immunotherapy of cancer. AB - We attempted to grow tumor-infiltrating lymphocytes (TIL) from 34 fresh tumors of eight different histologies using flasks for the initiation phase and hollow fiber bioreactors to expand TIL to therapeutic numbers. Overall success rate was 76% (26/34) including melanoma (9/14, 64%) and renal cell carcinoma (11/11, 100%). The mean number of days required to reach successful initiation (1 x 10(9) TIL) for all tumor types was 29 +/- 16 days (mean +/- S.D.). Therapeutic doses of TIL required an average of 88 +/- 23 days (initiation plus expansion) with an average TIL number of 3.2 x 10(10) +/- 2.8 x 10(10). TIL phenotype was predominantly CD4+ in 53% (16/30) and CD8+ in 47% (14/30), renal cell carcinoma samples accounted for 12/14 of the predominantly CD8+ TIL. Cells bearing the natural killer (NK) phenotype represented only 0-7% of TIL while LAK phenotype represented 0-68% (mean 11 +/- 15%); LAK was the predominant phenotype in one patient with kidney cancer. Cytotoxicity tests showed consistent NK and LAK activity in addition to cytolysis of autologous tumor. Autologous tumor cell restricted cytolysis was noted for three TIL cultures. The overall success rate and characteristics of TIL were similar to our results with TIL expanded in semi permeable plastic bags. This work confirms that hollow-fiber bioreactors are a suitable alternative to semi-permeable bags and roller bottle systems for the expansion of human TIL for therapeutic use in cancer patients. PMID- 11776756 TI - Optimizing radioimmunotherapy by matching dose distribution with tumor structure using 3D reconstructions of serial images. AB - The biological effect of radioimmunotherapy (RIT) is most commonly assessed in terms of the absorbed radiation dose. In tumor, conventional dosimetry methods assume a uniform radionuclide and calculate a mean dose throughout the tumor. However, the vasculature of solid tumors tends to be highly irregular and the systemic delivery of antibodies is therefore heterogeneous. Tumor-specific antibodies preferentially localize in the viable, radiosensitive parts of the tumor whereas non-specific antibodies can penetrate into the necrosis where the dose is wasted. As a result, the observed biological effect can be very different to the predicted effect from conventional dose estimates. The purpose of this study is to assess the potential for optimizing the biological effect of RIT by matching the dose-distribution with tumor structure through the selection of appropriate antibodies and radionuclides. Storage phosphor plate technology was used to acquire images of the antibody distribution in serial tumor sections. Images of the distributions of a trivalent (TFM), bivalent (A5B7-IgG), monovalent (MFE-23) and a non-specific antibody (MOPC) were obtained. These images were registered with corresponding images showing tumor morphology. Serial images were reconstructed to form 3D maps of the antibody distribution and tumor structure. Convolution of the image of antibody distribution with beta dose point kernals generated dose-rate distributions for 14C, 131I and 90Y. These were statistically compared with the tumor structure. The highest correlation was obtained for the multivalent antibodies combined with 131I, due to specific retention in viable areas of tumor coupled with the fact that much of the dose was deposted locally. With decreasing avidity the correlation also decreased and with the non-specific antibody this correlation was negative, indicating higher concentrations in the necrotic regions. In conclusion, the dose distribution can be optimized in tumor by selecting the appropriate antibodies and radionuclides. This has the potential to lead to a considerable enhancement of the efficacy of RIT in the clinic. PMID- 11776757 TI - HLA phenotype and cytokine-induced tumor control in advanced renal cell cancer. AB - BACKGROUND: The natural history of malignancies, the response to cytokine-based therapy and survival of patients may be partly determined by the human leukocyte antigen (HLA) phenotype. Here, we investigated in a retrospective analysis the correlation of the HLA phenotype of 73 prognostic favored patients with advanced renal cell carcinoma to (a) the expected HLA distribution in Caucasians, (b) the susceptibility or resistance to metastatic sites, (c) response to cytokine-based therapy and (d) sustained cytokine-induced effective tumor control. METHODS: We retrospectively determined the MHC class I and II antigens in patients with metastatic renal cell carcinoma selected by survival. Antigens were serologically typed by standard lymphocytotoxicity techniques. For statistical analysis, we calculated the probability of the presented HLA antigens in correlation to the expected Caucasian HLA phenotypes. An independent confirmation was performed by using the chi-square and two-tailed Fisher's exact test. RESULTS: Various HLA antigens deviated significantly from the normal distribution in the Caucasian population. HLA.B44 was the only antigen associated (p < 0.01) with the absence of lung and presence of bone metastases, while it did not impact on overall survival or response to therapy. A1 (p < 0.0001, p < 0.002) and B8 (p < 0.009, p < 0.04) alleles were more frequently expressed in responding patients than expected from the normal distribution in Caucasians and that observed in non responding patients, respectively. The HLA analysis of patients achieving a durable complete remission showed a significantly higher frequency of expression of the A1 and B8 antigens and furthermore of the B14 antigen (p < 0.05). CONCLUSIONS: Our data underline the pivotal role of the MHC complex in controlling and regulating the cellular immune response in renal cell cancer. We could identify HLA antigens, which correlate with response to cytokine-treatment, with a long-lasting effective tumor control and prolonged overall survival. PMID- 11776758 TI - Cationic liposomes enhance cellular/nuclear localization of 99mTc-antisense oligonucleotides in target tumor cells. AB - Efforts are underway to apply strategies developed in connection with antisense chemotherapy to antisense imaging in nuclear medicine. One such strategy is the use of cationic liposome to enhance the cellular uptake of antisense oligonucleotides. METHODS: Using a 99mTc-labeled 18-mer uniformly phosphorothioate DNA antisense to the mRNA of the RI alpha subunit of PKA, the effects of a cationic liposome as carrier on cell uptake and efflux kinetics in tissue culture was evaluated in a RI alpha mRNA positive ACHN cell line. The sense DNA was used as control. RESULTS: Cell uptake was increased 4-5 fold using the liposome carrier compared to the same dosage of naked DNA. Whether naked or liposome-bound, the antisense DNA showed slower efflux from cells compared to the control, resulting in statistically higher accumulation of the antisense compared to the control DNA and suggesting an antisense effect. The internalization and increased cellular accumulation for both antisense and control DNAs with liposomes were demonstrated by microautoradiography and by subcellular fractionation. Finally, using 99mTc-labeled 15-mer antisense DNA against the c myc oncogene mRNA in MDA-MB-231 cells, significantly more radiolabel was found in total mRNA for the antisense compared to the sense control DNA, both with and without liposome carrier. In conclusion, in tissue culture, the use of a cationic liposome carrier greatly increased cellular uptake and target mRNA binding of 99mTc-labeled antisense DNA. PMID- 11776759 TI - BCL2 antisense transcripts decrease intracellular Bcl2 expression and sensitize LNCaP prostate cancer cells to apoptosis-inducing agents. AB - Prostate cancer (CaP) is the most commonly diagnosed cancer of aging men and the second leading cause of male cancer death in the United States. At present, no effective therapy is available for treating hormone independent CaP. Since Bcl2 is believed to play a role in protecting CaP cells from apoptosis, we investigated the effects of down-regulating Bcl2 expression on CaP cells. Genetically engineered LNCaP sublines were established by stably transfecting LNCaP cells with BCL2 antisense (BCL2-AS) transcript-expressing plasmids. Western blotting analysis showed that intracellular Bcl2 protein was decreased by 50-60% in BCL2-AS-transfected LNCaP cells. Expression of the antisense transcripts resulted in 50% growth inhibition of LNCaP cells in response to androgen withdrawal and markedly sensitized these cells to Adriamycin-induced apoptosis. These results suggest that down-regulation of Bcl2 protein using BCL2-AS transcripts could be exploited for improved treatment of advanced CaP. PMID- 11776760 TI - In vitro effect of gelatins on murine cell proliferation. AB - Porcine skin (PS) gelatin suppressed proliferation of a murine hepatic cell carcinoma cell line, MH134, a murine fibrosarcoma cell line, Meth A and a murine T cell lymphoma cell line, RL Male 1. The magnitude of suppression of the proliferation by cold water fish skin (CWFS) or bovine bone (BB) gelatin was lower than that by PS gelatin. On the other hand, BB gelatin stimulated proliferation of murine spleen cells. The magnitude of stimulation of the proliferation by CWFS gelatin was lower than that by BB gelatin. PS gelatin slightly suppressed proliferation of murine spleen cells. PS gelatin induced apoptosis but not necrosis of MH134 tumor cells. CWFS gelatin induced weaker apoptosis of the cells than PS gelatin. DNA histogram indicated that PS and CWFS gelatins acted on MH134 tumor cells to increase ratios of G2 + M-phase. PMID- 11776761 TI - Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis. AB - The mistletoe lectins are major active components in the extract of European mistletoes that have been widely used in adjuvant chemotherapy of cancer. This study was performed to investigate the mechanism of anticancer and antimetastatic activity of the purified Korean mistletoe lectin (Viscum album L. coloratum agglutinin, VCA). C57BL6 mice inoculated with B16-BL6 melanoma cells and treated with VCA were assessed for survival and metastasis. The induction of apoptosis of B16-BL6 cells by VCA was investigated by morphological changes, DNA fragmentation characteristics, and cell cycle analysis. The antiangiogenic activity of VCA was also measured by the CAM (choriallantoic membrane) assay. Length of survival of mice was increased and lung metastasis was inhibited by VCA. Treatment of cells with VCA resulted in growth suppression, nuclear morphological changes, DNA fragmentation, and an increased fraction of cells in sub-G1 consistent with apoptosis. Antiangiogenesis of VCA was assessed by CAM assay, where vessel growth induced by fat emulsion was decreased. These results suggest that VCA inhibits tumor growth and metastasis by increasing apoptosis and inhibiting angiogenesis. PMID- 11776762 TI - [Effects of tracheal gas insufflation on blood gases and respiratory mechanics in acute hypercapnia rabbits]. AB - OBJECTIVE: To evaluate the effects of tracheal gas insufflation (TGI) on elimination of CO2 and improvement of ventilation efficiency. METHODS: Using self designed TGI device, physiological parameters such as PaCO2, Ppeak, Ppause, end expiratory carbondioxide pressure (PetCO2), lung statistic compliance(Cst), respiratory resistance(Re) and expiratory lung volume(VE) in the two animal groups of conventional mechanical ventilation (CMV) and hypercapnia (HC) by applying two different TGI flow(0.2 L/min and 0.4 L/min) were observed. RESULTS: TGI can significantly decrease the PaCO2 level, enhance CO2 elimination and maintain PaCO2 in the normal range while decreasing VT by 30%, the eliminating effect of CO2 is flow dependent. TGI can elevate airway pressure in both animal groups, but the level of Ppeak, Ppause in HC group are significantly lower than those of CMV group. PetCO2 levels are significantly decreased after TGI while Re and VE increased significantly after TGI. TGI shows no obvious influence on Cst, mean arterial pressure and heart rate. CONCLUSIONS: Our results reveals that TGI is a simple and practical adjunct method to mechanical ventilation, it can effectively decrease PaCO2, and maintain low airway pressure. PMID- 11776763 TI - [Continuous tracheal gas insufflation during pressure control ventilation with a pressure relief valve]. AB - OBJECTIVE: To establish the method of continuous tracheal gas insufflation (CTGI) and investigate the role of pressure relief valve (PRV) in limiting high peak airway pressure induced by CTGI. METHODS: CTGI device was made by authors. Nine healthy mongrel dogs were mechanically ventilated by using Evita 2 (Drager Inc.). PRV was inserted into the ventilatory circuit for selected experiment steps and adjusted a threshold pressure equal to the preset inspiratory pressure. PCV, PCV + CTGI (TGI group) and PCV + CTGI + PRV (PRV group) were conducted in different inspiration/expiration (I/E) ratio of 1:2 and 2:1. Gas exchange, lung mechanics and hemodynamics status were monitored at the constant set inspiratory pressure of PCV. RESULTS: At the same I/E ratio, peak airway pressure in TGI group was higher than that of PRV and PCV group (P < 0.01), whereas PRV group maintained the preset inspiratory pressure as PCV group. At the different I/E ratio, peak airway pressure in TGI (2:1) group was higher than that of TGI (1:2) group(P < 0.01). PaCO2 in TGI and PRV group decreased significantly than that of PCV, TGI group was more lower than PRV group, PaO2, hemodynamics and oxygenation remained unchanged in all groups. CONCLUSIONS: The CTGI device is effective in improving alveolar ventilation with no significant influence on hemodynamics and oxygenation; A pressure relief valve is necessary to ensure the safe use of CTGI. PMID- 11776764 TI - [A preliminary study on the markers of pulmonary vascular endothelial cells in patients with ARDS]. AB - OBJECTIVE: To explore the changes of the markers of pulmonary vascular endothelial cell (PVEC) in patients with ARDS. METHODS: The levels of plasma circulating endothelial cell(CEC), granule membrane protein-140(GMP-140), endothelin-1(ET-1) and von Willebrand factor (vWF) were determined respectively in 13cases of ARDS. The vWF on the surface of the PVEC were stained in 5 cases of ARDS. RESULTS: Circulating CEC, GMP-140, ET-1 and vWF levels were increased significantly (P < 0.01) but scores of vWF expression on the PVEC became weak (P < 0.01) in ARDS samples. The level of plasma GMP-140 elevated dramatically in 2nd day( > 4 times). CONCLUSIONS: PVEC are severely impaired during ARDS. GMP-140 released from PVEC might be a satisfactory criteria for early surveillance and for evaluation of prognosis of ARDS in clinical practice. PMID- 11776765 TI - [The combined therapy of carboplatin, fluorouracil and radiotherapy for moderate and advanced non-small cell lung cancer]. AB - OBJECTIVE: To observe the effect of combined chemotherapy (carboplatin and fluorouracil) with radiotherapy for moderate and advanced non-small cell lung cancer. METHODS: Eighty patients with moderate and advanced non-small cell lung cancer were randomized into 2 groups, radiotherapy group(R) and carboplatin, fluorouracil plus radiotherapy group (CF + R). All patients in two groups received conventional radiotherapy. Patients in CF + R group received combined chemotherapy with carboplatin(100 mg, d 1-5) 5-fluorouracil(500 mg d 1-5) in the first and fourth weeks during radiotherapy. RESULTS: The complete response rate was 48% in CF + R group, 25% in R group. The 1-year, 3-year, 5-year survival rates were 63%, 38%, 18% in CF + R group, and 40%, 15%, 8% in R group. The major toxic reactions in CF + R group were grade I-II myelo-suppression and digestive tract reaction. CONCLUSIONS: Combined chemotherapy(carboplatin and fluorouracil) with radiotherapy is preferable for non-small cell lung cancer. PMID- 11776766 TI - [Correlation between the expression of vascular endothelial growth factor and prognosis of lung cancinoma]. AB - OBJECTIVE: To determine the association between the expression of vascular endothelial growth factor (VEGF) and prognosis of lung cancer. METHODS: Apply the SP immunohistochemistry stain method to investigate the expression of VEGF in 60 specimens of patients with lung cancer, who had undergone curative resection more than 36 months before. RESULTS: The VEGF stain positive rate is 60% in 60 cases of lung cancer specimens; The immunoreactivity of VEGF was almost exclusively restricted to the tumor cells, the positive expression of VEGF showed significantly higher in the patients with lymph node metastasis and/or relapse. The positive rates of VEGF were higher in N1, N2 groups (53%, 80%) than in No group (23%, P < 0.01), and in relapse group (80%) than in non-relapse group (53%, P < 0.05). Postoperative survival time was shorter in VEGF(+) group (31 +/- 7 months) than in VEGF(-) group (64 +/- 7 months, P < 0.05). The 3, 5 year survival rates showed significant difference between VEGF(+) (31%, 11%) and VEGF(-) (88%, 50%) groups. CONCLUSIONS: The results suggest VEGF is a reliable prognostic parameter and antiangiogenesis therapy will be a useful strategy in treatment of the human lung cancer. PMID- 11776767 TI - [The clinical analysis and review of literature of pulmonary carcinosarcoma and blastoma]. AB - OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment of pulmonary carcinosarcoma and blastoma. METHODS: Summarizing retrospectively 15 cases of pulmonary carcinosarcoma and 2 cases of pulmonary blastoma from January 1979 to November 1998, and reviewing literature to analyse their histologic, clinical feature, diagnosis and treatment. RESULTS: Pulmonary carcinosarcoma and blastoma both were found to be rare malignant tumors, and both epithelial and mesenchymal elements can be seen under the microscopy with different characteristic features. It was hard to be diagnosed before operation. The main symptoms of pulmonary carcinosarcoma were cough, expectoration, sometimes bloody phlegm. X-ray showed that peripheral type were most common, and 2-5 cm in size, well-distributed in density, some showed central or eccentric cavities whose wall was irregular. The margin of the focuses were clear, leafy, the distensive lymph nodes of hilum or mediastium could also be seen. Bronchoscopic examination revealed the bronchial cavity was obstructed by mass or became stricted. Local biopsy can found squamous, adenocarcinoma or large cell carcinoma, respectively. Malignant cell can also be found in sputum. So it was easy to be confused with lung cancer. 14 cases of the carcinosarcoma were treated surgically and diagnosed, 1 case was diagnosed by lymph node biopsy. The symptoms of pulmonary blastoma were fever and hemoptysis. X-ray or CT scan showed an isolated mass in the lung, with uneven density. Malignant cells in pleural effusion were found in one case and can not be diagnosed definetely but by pulmonary puncture. The another case was diagnosed by surgical operation. 15 cases of this group were followed up, in which 4 cases are still alive (including 1 case of pulmonary blastoma), the 1-year survival of carcinosarcoma is 30% (3/10), 2-year survival 20% (2/10), in which 1 case survived more than 6 years. Another pulmonary blastoma case only survived 3 months. CONCLUSIONS: These 2 kinds of malignant tumor are often easy to be misdiagnosed, and prognosis is very poor. Surgical resection is the main method of diagnosis and treatment. PMID- 11776768 TI - [The expression of MRP gene relates to the pathological features of lung cancer]. AB - OBJECTIVE: To evaluate the expression of MRP gene and its relation to pathological features in lung carcinoma. METHODS: A series of 35 resected primary lung cancer tissues from 9 post-chemotherapy and 26 untreated patients and adjacent normal lung tissues and 28 lymph node tissues were analyzed for MRP gene expression by RT-PCR method. RESULTS: Positive expression rate of MRP gene was 54% in 35 cases with primary lung cancer, 14% in tissues adjacent to the carcinoma site and the difference was significant (P < 0.005), the positive rate of MRP gene expression in metastatic lymph node tissues was 53%. In 9 cases of pre-operative chemotherapy, the positive expression rate of MRP gene was higher than that in 26 cases without chemotherapy. Nineteen of 35 tumors were found to show positive expression of MRP gene, comprising 11 of 18 adenocarcinoma, 9 of 15 squamous cell cancer. The relapse or metastasis rate with MRP-positive cases was higher(55%) than that with MRP-negative (15%) by follow-up of these patients. CONCLUSIONS: There are overexpression of MRP gene in primary lung cancer tissues. Preoperative chemotherapy may play inductive role in lung cancer multidrug resistance. The positive expression of MRP gene in lung cancer tissues is in accord with its lymph node tissues. Positive expression of MRP gene does not necessarily be associated with tumor size, clinical type and TNM stages, but it could be regarded as one poor prognostic factor. PMID- 11776769 TI - [Study on inflammatory response and alteration of biochemical components in BALF from Pneumocystis carinii pneumonia]. AB - OBJECTIVE: To study the cellular and biochemical changes in airways in pneumocystis carinii pneumonia (PCP). METHODS: The cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) between PCP and bacterial pneumonia in rat models induced by cortisone acetate(GC) injections were compared. The activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and type IV collagenase(matrix metalloproteinases, MMP-2, MMP-9) in BALF were measured. The rats were divided into four groups: (1) normal controls: 6 healthy SD rats; (2) negative control: 6 rats with GC injection over 8 weeks without lung infection; (3) bacterial pneumonia: 11 rats with GC injection over 8 weeks complicating bacterial pneumonia without other pathogens isolated; (4) PCP: 14 rats with GC injection during 8-12 weeks complicating PCP without other pathogens isolated. RESULTS: In PCP the total cell counts (6.9 +/- 2.6) x 10(6)/L and the percentage of PMNs (18.6 +/- 6.0)% in BALF were increased compared with negative control(P < 0.01), but were lower than those in bacterial pneumonia group(P < 0.01). ALB in BALF in PCP (623 +/- 484) g/L was increased compared with negative control (36 +/- 16) g/L(P < 0.05) and bacterial pneumonia(91 +/- 43) g/L(P < 0.05). The activities of ALP and LDH in PCP [(217 +/- 81) U/L, (208 +/- 82) U/L respectively] were higher than those in negative control [(75 +/- 37) U/L, (86 +/- 61) U/L, P < 0.05)] and bacterial pneumonia [(90 +/- 45) U/L, (130 +/- 75) U/L, P < 0.05]. The activities of Type IV collagenase, including MMP-2, MMP-9, were increased in PCP compared with negative control (P < 0.001) and bacterial pneumonia (P < 0.001, P < 0.01), and the activities of MMP-2 and MMP-9 had positive correlations with total cell counts in BALF (r = 0.652, P < 0.05; r = 0.803, P < 0.001). CONCLUSIONS: It suggests that there are differences in the cellular and biochemical aspects of lung inflammation and injury between PCP and bacterial pneumonia. PMID- 11776770 TI - [Forty-seven cases of lower respiratory tract infections due to E. ictaluri]. AB - OBJECTIVE: To study the risk factors and treatment of lower respiratory tract infections due to E. ictaluri, and the cause of its improved detection by sputum culture in recent years. METHODS: To sum up the number of positive cultures and analyze the clinical features of the cases with positive sputum culture tested from 1959 to 1998. RESULTS: Before 1996, there were no positive cultures (0%) in 17,500 sputum samples using manual techniques, in 1997 and 1998 the aggregate positive rate was 2.3% (47/1,962), using SCEPTOR detecting instrument. On chi square testing of the two results derived from the two methods, P < 0.001. On drug sensitivity testing, E. ictaluri was sensitive to imipenem, cefotaxime and tobramycin. CONCLUSIONS: E. ictaluri is an uncommon opportunistic pathogen of lower respiratory tract infections. Lowered body resistance is a risk factor, and improved technology is the principal cause for detection of E. ictaluri infections. PMID- 11776771 TI - [Lymphocyte apoptosis in asthmatic patients and its molecular mechanism]. AB - OBJECTIVE: To assess the apoptosis rate of peripheral blood lymphocytes isolated from patients with asthma and explore its molecular mechanism. METHODS: Lymphocytes were isolated with ficoll-hypaque gradient method and T lymphocytes were further isolated with nylon pili. T lymphocytes were stimulated by anti- CD3+ antibody for 0, 24, 48, 72 hours in vitro and the apoptosis rates were measured with in situ tailing technique. At the same time, Bcl-2 gene expression and Bax gene expression were observed with in situ hybridization. RESULTS: The percentages of apoptosis cell in T lymphocytes from patients with asthma were significantly decreased and the timing delayed in comparison with those in normal controls (P < 0.01). The Bcl-2 mRNA expression in T lymphocytes was significantly increased in different time points than in normal controls (P < 0.01), but Bax mRNA expression in T lymphocytes was remarkably decreased (P < 0.01). The rates of Bcl-2/Bax mRNA could not reach the state of the controls until 72 hours from the begining of the stimulation with the anti-CD3+. CONCLUSIONS: The inhibited apoptosis might be one of the reasons for the chronic persistent inflammation in the airways in asthmatic patients and the imbalance between Bcl-2 gene expression and Bax gene expression may be one of the molecular mechanisms for the inhibited apoptosis. PMID- 11776772 TI - [Changes of calcitonin gene-related peptide content in induced sputum from patients with COPD and asthma]. AB - OBJECTIVE: To explore the role of sensory neuropeptide calcitonin gene-related peptide (CGRP) in the pathogenesis of chronic airway inflammatory diseases COPD and bronchial asthma. METHODS: Patients with COPD (n = 19), bronchial asthma (n = 14), all were in stable stage and 10 normal volunteers were examined. After hypertonic saline inhalation challenge in all subjects, CGRP-LI concentration in the induced sputum was measured by radioimmunoassay. Cellular content was assayed by microscopic analysis, the relation between CGRP-LI level and FEV1 value was calculated by linear regression. RESULTS: The sputum CGRP concentrations in patients with COPD and patients with asthma were (15.97 +/- 2.15) ng/L, (18.79 +/ 3.91) ng/L, respectively, both were significantly higher than those in normal volunteers (2.36 +/- 0.35) ng/L. Moreover, CGRP concentrations in induced sputum in each disease group were correlated with the degree of airflow obstruction, r = -0.50 and -0.61, respectively (P < 0.05). The percentage of neutrophil cell count (64.9 +/- 2.9)% was significantly higher in patients with COPD (P < 0.01), while the percentage of eosinophil cell count (5.8 +/- 0.5)% was increased in patients with asthma (P < 0.01). CONCLUSIONS: The data suggested that CGRP release may participate in the chronic inflammation of patients with COPD and bronchial asthma. PMID- 11776773 TI - [Cleaning cavity operation in treating relapse bacillary cavitary pulmonary tuberculosis]. AB - OBJECTIVE: To study the effective surgical way for serious relapse multidrug resistant bacillary cavitary pulmonary tuberculosis. METHODS: 104 cases of serious relapse multidrug resistant bacillary cavitary pulmonary tuberculosis were cured by cleaning cavity operation from 1981 to 1998. The operation contained resecting the back rib covering the cavity, separating the intercostal tissue, cutting the external wall of the cavity, cleaning the cavity thoroughly, scraping the cavity till exposing the fresh tissue, killing the tuberculosis germs with organic acid, filling the cavity with the intercostal muscle, fixing and suturing the muscles. RESULTS: Among the 104 cases, 103 cases (99.0%) were cured, 101 cases (98.1%) were cured after the first operation, one case (1.0%) became better. Among the 98 cases followed up, the rate of returning to work were 96%, no one died or relapsed. CONCLUSIONS: The design of cleaning cavity operation is reasonable and it is the effective method to treat the relapse bacillary cavitary pulmonary tuberculosis, the rate of cure and sputum conversion are promising. PMID- 11776774 TI - [Bronchial asthma, allergic rhinitis and atopy]. PMID- 11776775 TI - [Is the asthma caused by self-diagnosed "common cold" reliable]. AB - OBJECTIVE: To investigate the incidence of allergic rhinitis (AR) in the patients with asthma induced by the common cold, diagnosed by the patients themselves, and the relationship between AR and asthma. METHODS: All the patients were inquired and examined in details, including counting the eosiphils in the smear of the nasal secretion and allergen skin test. RESULTS: 49(47.6%) out of 103 asthmatics with so-called common cold were diagnosed as AR. The average of the initial asthmatic episode in asthmatics with AR were significantly younger than that in patients without AR, (28 +/- 13) and (36 +/- 16) years, respectively (P < 0.01). There was concordance between asthma and AR on seasonal regularity of episode. CONCLUSIONS: (1) In large portion of asthma, common cold diagnosed by patients themselves actually is AR; (2) There is a close relationship between AR and asthma; (3) It is important for physicians to distinguish AR from common cold in asthmatics. PMID- 11776776 TI - [Study on serotyping of Haemophilus influenzae and the positive rates of beta lactamase]. AB - OBJECTIVE: To investigate the serotypes of both infectious and carriage strains of Haemophilus influenzae (Hi) and to evaluate the prevalence of beta-lactamase of major serotypes in Shanghai. METHODS: The 534 specimens of sputum and swabs from patients with acute upper or lower respiratory tract infection and 255 cases of control group were collected and incubated on improved Collumbia chocolate medium. All isolated Haemophilus influenzae strains were serotyped by slide agglutinating assay or reverse indirect blood agglutinating method. beta lactamase were measured by iodine test and paper disc method. RESULTS: In the patient group, of the 164 Hi strains there were 69 Hib strains (42%, 69/164) and 91 NTHi(56%, 91/164). In the control group, there were 14 strains of Hib and 49 strains of NTHi among 66 strains of Hi, which were isolated from 255 specimens(26%, 66/255). 24%(38/160) of Hi in the patient group produced beta lactamase. In this group, the positive rate of beta-lactamase was 29%(20/69) for Hib strains and 20%(18/91) for NTHi strains. Sixteen strains resisting to ampicillin were beta-lactamase negative. CONCLUSIONS: These results indicate that Hib and NTHi are the major serotypes of Hi in both the patient and control group. The prevalence of Hib is higher in patients than in the control. Hib strains are more likely to produce beta-lactamase than NTHi. PMID- 11776777 TI - [The role of endogenous nitric oxide in airway hyperresponsiveness of asthmatic rats]. AB - OBJECTIVE: Nitric oxide (NO) precursor L-arginine (L-Arg) and NOS inhibitor NG nitro-L-arginine methyl ester (L-NAME) were used to investigate the role of endogenous NO in airway hyperresponsiveness of asthmatic rats. METHODS: Asthmatic wistar rats were developed by sensitization and challenging with ovalbumin. Airway responsivess to acetylcholine (Ach) was measured in vitro in isolated and perfused rat tracheal rings with or without epithelium after inhibiting or stimulating NO synthesis. RESULTS: After asthmatic rat tracheal rings were incubated in vitro with L-NAME 10(-5) mol/L, the maximal response of tracheal rings to Ach was increased compared with that of the control group. When asthmatic rat tracheal rings were coincubated with L-Arginine 2 x 10(-5) mol/L and L-NAME 10(-5) mol/L, the maximal response was decreased compared with that of the L-NAME group. Incubation with higher concentrations of L-Arginine did not change asthmatic rat tracheal responsiveness to Ach. Epithelium-denuded tracheal rings in the asthmatic rats showed a significant (P < 0.05) upward shift in the Ach concentration response curve; the maximal response was increased compared with the tracheal intact group. In the denuded tracheal rings, L-NAME and L Arginine did not influence the shape of the Ach concentration-response curve and the maximal response. CONCLUSIONS: Endogenous nitric oxide, a mediator of bronchodilation, is synthesized from L-Arginine by NO synthase in asthmatic rats. The epithelium lining airway smooth muscle probably contributes to nitric oxide synthesis. Our finding suggests that the airway in asthmatic rats could not use exogenous L-Arginine to synthesize nitric oxide. PMID- 11776778 TI - [A study on the roles of CD86 in antigen-induced eosinophil infiltration into airways and airway hyperresponsiveness]. AB - OBJECTIVE: To explore the effect of CD86 on antigen-induced eosinophil infiltration into the airways and airway hyperresponsiveness in sensitized mice, and further elucidate the role of CD86 in the pathogenesis of bronchial asthma. METHODS: Female BALB/c mice (n = 8 for each group) were sensitized and challenged with ovalbumin to induce airway eosinophilia and airway hyperresponsiveness. Airway responsiveness was espressed by the provocative concentration of acetylcholine causing 50% increase in respiratory resistance (PC50). Effect of anti-CD86 monoclonal antibody (mAb) on antigen-induced changes of eosinophil numbers in brochoalveolar lavage fluid (BALF) and airway reactivity was observed. CD86 expression on BALF cells was detected by flow cytometry and concentrations of interleukin-4 and interleukin-5 in homogenized supernatant of lung tissue were determined by ELISA. RESULTS: In sensitized mice challenged with ovalbumin 20 minutes once a day for 6 days, the number of BALF eosinophils was (9.2 +/- 1.5) x 10(8)/L. However, no eosinophil could be found in the BALF from mice without ovalbumin sensitization and challenge. Also, ovalbumin treatment led to PC50 value decrease from (0.66 +/- 0.13) g/L to (0.17 +/- 0.07) g/L (P < 0.01). CD86 expression on BALF cells from ovalbumin sensitized- and challenged-mice (36.4 +/- 6.2) was much higher than that from control mice (12.3 +/- 3.6, P < 0.01). In mice treated with intravenous injection of anti-CD86 mAb before each challenge, BALF eosinophils decreased by 67% (P < 0.01), and PC50 value increased by 69% (P < 0.01). Our results showed that anti-CD86 mAb prevented antigen-induced airway eosinophilia and airway hyperresponsiveness accompanied by a decrement of levels of both interleukin-4 and interleukin-5 in lung tissue. CONCLUSIONS: Anti-CD86 mAb is able to inhibit antigen-induced airway eosinophilia and to ameliorate airway hyperresponsiveness, possibly by inhibiting production of interleukin-4 and interleukin-5. These data suggested that the blockade of airway antigen presenting cells' functions couid be of value in treatment of human asthma. PMID- 11776779 TI - [The effect of erythromycin on NF-kappa B activation and cytokines mRNA expression in bleomycin-induced pulmonary fibrosis in rats]. AB - OBJECTIVE: To evaluate the effect of erythromycin (EM) on nuclear factor-kappa B (NF-kappa B) activation and cytokines mRNA expression in bleomycin-induced pulmonary fibrosis in rats. METHODS: Wistar rats were divided into three groups of 27 as follow: BLM-group received intratracheal instillation of single dose BLM 5 mg/kg. EM treated-group received intratracheal instillation of BLM 5 mg/kg and an oral instillation EM 100 mg.kg-1.d-1. Control group received intratracheal and oral instillation of normal saline. Animals of all three groups were sacrificed on the 4th, 7th and the 28th day separately. NF-kappa B activation in alveolar macrophages (AM) was investigated by electrophoretic mobility shift assay. The expressions of IL-1 beta and TGF-beta mRNA in lung were evaluated by Northern blot analysis. The pathological changes of lung tissue were analyzed quantitatively by computer gray scan. RESULTS: On the 4th and 7th day, the activities of NF-kappa B in AM were significantly increased in BLM-group compared with those of control group (P < 0.05), while they were significantly decreased in EM treated-group compared with BLM-group (P < 0.05). On the 7th day, the expressions of IL-1 beta and TGF-beta mRNA in lung were significantly decreased in EM treated-group compared with those in BLM-group. Pathologically, EM decreased exudation of inflammatory cells in the early response as well as degree of fibrosis in the late stage in the BLM-induced pulmonary fibrosis. CONCLUSIONS: These results indicate that NF-kappa B is involved in the inflammatory response in BLM-induced pulmonary fibrosis in rats, EM has inhibitory effect on NF-kappa B activation, IL-1 beta and TGF-beta mRNA expression, by which it ameliorated acute lung injury and fibrosis those tested rats. PMID- 11776780 TI - [Study on epidemic of drug-resistant tuberculosis in Shandong province, China]. AB - OBJECTIVE: To establish the surveillance system for drug resistance of tuberculosis according to WHO and IUATLD guidelines, and to evaluate the initial and acquired drug resistance in Shandong province. METHODS: 30 of 141 counties/cities were randomly selected as surveillance points by cluster sampling from April to October 1997, in each of which 36 cases with smear positive pulmonary tuberculosis were continuously observed. Identification and susceptibility tests were done in all culture positive samples. RESULTS: The total frequency of drug resistance was 23.4%, initial drug resistance 17.6%, initial multi-drug resistance 2.9%, acquired drug resistance 50.0%, acquired multi-drug resistance 19.6%. CONCLUSIONS: The results suggest that the initial drug resistance still ranks high in Shandong province, National TB Control Program should be further strengthened. PMID- 11776781 TI - [Differential diagnosis in patients with tuberculous meningitis and cryptococcal meningitis]. AB - OBJECTIVE: To search for the main differential points in clinical and CSF changes between patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM). METHODS: Fifty three cases of TBM and 55 cases of CCM who admitted to hospital from February 1983 to December 1997 were investigated retrospectively. Main symptoms, signs and CSF changes before administration of specific antibiotics were compared. RESULTS: 9%(5/53) TBM and 49% (27/55) CCM patients had headache without fever at the onset. The incidences of symptoms of failing eyesight, hearing loss and paralysis of extremities were 13% (7/53) and 36%(20/55), 2% (1/53) and 16% (9/55), and 19% (10/53) and 0 in TBM and CCM patients respectively. The rate and the degrees of optic papilla edema in CCM patients (66%, 16/36 slight, 13/36 moderate, and 7/36 serious) were significantly higher and more serious than that in TBM (15%, 8/8 slight). The patients with initial CSF pressure over 400 mm H2O were 11% and 90% in TBM and CCM. All but 20 CCM patients had elevation of CSF protein content, and 45% (24/53) TBM and 9%(5/55) CCM were > 2 g/L. CONCLUSIONS: This study shows that the most important differences between TBM and CCM are: headache not accompanied by fever at the onset, failing eyesight, striking elevation of initial CSF pressure, moderately and serious degree of optic papilla edema, normal CSF protein content occurs usually in CCM more than those in TBM patients. On the other hand, striking elevation of CSF protein content (> 2 g/L) occurs usually in TBM patients. PMID- 11776782 TI - [Respiratory effects of beta-endorphin in chronic hypoxic rats]. AB - OBJECTIVE: To assess the role of beta-EP in the physiological and pathophysiological process of respiratory regulation in chronic hypoxic rats. METHODS: The chronic hypoxic rat model was established by intravenous injections of papain 6 times, once a week. The concentration of beta-endorphin in medulla, pons, hypothalamus, central gray and plasma of chronic hypoxic rats were measured by radioimmunoassay. All animals were pretreated with sodium pentobartital (35 mg/kg) before experiment. 102 rats were randomly divided into three groups. Group 1 (n = 36). The respiratory rate (RR) and tidal volume (VT) were measured after intravenous injection of naloxone (NLX, 2 mg/kg), beta-EP (40 micrograms/kg, 160 micrograms/kg) or normal saline, Group 2 (n = 48). By the intracerebroventricular administration of NLX and beta-EP to the models, RR, VT and PaCO2 were observed after microinjection 5, 15, 30, 45, 60 min. Group 3 (n = 18). The respiratory effects of beta-EP after directly into the nucleus tractus solitari of the anaesthetised rats were investigated. RESULTS: The beta-EP contents in medulla, pons, hypothalamus, central gray and plasma of chronic hypoxic rats were significantly increased compared with control subjects (P < 0.01). It suggested that the pathophysiology of chronic hypoxic process infleuced the contents of beta-EP in the CNS and plasma in rats. Intracerebroventricular microinjection of beta-EP in normal rats, resulted in a significant decrease in RR (P < 0.05). No significant difference in RR and VT was observved after intravenous injection of naloxone (2 mg/kg) and beta-EP (40 micrograms/kg, 160 micrograms/kg) in treatment group compared with the control group (P > 0.05), Intracerebroventricular microinjection of NLX in chronic hypoxic rats, resulted in a marked increase in RR (P < 0.05) and central hypercapnic-sensitivity (t = 2.76, P < 0.05), Intracerebroventriculalr microinjection of beta-EP in chronic hypoxic models, resulted in severe respiratory depression after injection 15, 30, 45, 60 min (RR t = 3.41, 6.54, 6.97, 7.87, P < 0.01; VT t = 3.07, 7.27, 6.14, 6.08). CONCLUSIONS: These results indicate the beta-endorphin may be involved in central respiratory control of chronic hypoxic rats. PMID- 11776783 TI - [The study on COPD rat model produced by bacterial infection]. AB - OBJECTIVE: To observe the role of bacterial infection in pathogenesis of COPD. METHODS: The COPD animal model was developed by intranasal repeated injecting Klebsiella pneumoniae(K) or pneumococcal pneumoniae(P) into rat respiratory tract. Histomorphyological changes were observed, PaO2, PaCO2 and right ventricular systolic pressure (RVSP) were analysed. RESULTS: 1 week after injecting K and 4 week after injecting P, the epithelia of bronchioles showed obvious injury. From the 4th week there was severe chronic inflammatory process of bronchioles in 2 experimental groups including thickened wall, narrowed lumen and developed emphysema. In addition, the walls of arterioles accompanying bronchioles were also thickened obviously. Right ventricular systolic pressure raised in 2 experimental groups (P < 0.01). From the 16th week, PaO2 dropped and PaCO2 raised in K group. CONCLUSIONS: Repeated injecting intranasally of the proper amount of klebsiella pneumoniae or pneumococcal pneumoniae into rats' lungs can induce rat small airway inflammation and emphysema. Combining with PaO2, PaCO2 and RVSP analysis, we suggest the model established shows main features of COPD. PMID- 11776784 TI - [Studies of microsatellite instability and loss of heterozygosity at chromosome 17 in non-small cell lung carcinoma]. AB - OBJECTIVE: To identify the presence of microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung carcinoma (NSCLC). METHODS: Four microsatellite markers TP53(17p13.1), THRA1 (17q11.2-12), D17S579(17q12-21) and D17S855(17q21) were used to examine 35 cases of NSCLC tumor-normal paired tissues for MI and LOH at chromosome 17 using PCR based analysis. RESULTS: 22 of 35 tumors(63%) displayed MI or LOH. 14 tumors(40%) exhibited MI, 11 tumors(31%) exhibited LOH, while 3 tumors (9%) exhibited MI and LOH concurrently. The frequency of MI or LOH was obviously higher in the early-stage(stages I and II, 79%) than in the advanced-stage (stage III, 44%), P < 0.05. However, the frequency of MI or LOH had no significant difference between high-grade differentiated NSCLC tumors and low-grade ones, P > 0.05. No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC, P > 0.05. CONCLUSIONS: The results suggest that MI and LOH at chromosome 17 may play a significant role in the development of NSCLC. The high frequency of MI or LOH in the early-stage tumors indicates that these genetic alterations could occur early during NSCLC development. PMID- 11776785 TI - [Mutations of several tumor suppressor genes in primary retinoblastoma]. AB - OBJECTIVE: To study the status of several tumor suppressor genes in primary retinoblastoma. METHODS: Single stranded conformation polymorphism (SSCP) analysis associated with direct DNA sequencing was used to identify point mutations in the coding sequence of Rb, p53, p16, p15 and p21 tumor suppressor genes, and multiplex PCR was used to detect big deletion in p16 and p15 genes. RESULTS: Rb gene point mutation was detected in 74% of retinoblastoma and p16 gene big deletions in 16% of retinoblastoma with or without Rb gene mutation. However, despite polymorphism, no real mutation was detected in p53 or p21 gene in retinoblastoma. CONCLUSION: The evidence from this study suggests that retinoblastoma is resulted exclusively from alterations of genes in Rb pathway. PMID- 11776786 TI - [Experimental study of interleukin-4 gene therapy for glioma]. AB - OBJECTIVE: To study IL-4 gene therapy for glioma. METHODS: Using recombinant retrovirus vector, mIL-4 was transfected into psi 2 packaging cells and rat C6 glioma cells, respectively by lipofectamine. The IL-4 secretting cell clones psi 2 IL-4 and C6IL-4 were studied in vitro and in vivo. RESULTS: Apart from a decrease in cloning efficiency, no difference was observed between the transfected and the wild type glioma cells in proliferation and cell cycle in vitro. Tumorigenicity of subcutaneously and intracranially inoculated C6IL-4 was reduced. Tumor growth could be suppressed by perineoplastic inoculation of psi 2 IL-4 cells. CONCLUSION: IL-4 gene-modified C6 glioma has decreased tumorigenicity. Local production of IL-4 by psi 2 IL-4 cells can lead to regression of established glioma. PMID- 11776787 TI - [The possible role of loss of heterozygosity at APC, MCC and DCC genetic loci in esophageal carcinoma]. AB - OBJECTIVE: To investigate the alterations of APC, MCC and DCC genes in human esophageal carcinoma. METHODS: A total of 46 human esophageal cancer specimens were analyzed for the loss of heterozygosity (LOH) at APC, MCC and DCC genetic loci by means of polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The incidence of LOH was 29.0%(9/31) at APC locus, 33.3%(8/24) at MCC locus, and 32.4%(12/37) at DCC locus, respectively. However, there was no statistically significant correlation between LOH at these three loci with such clinical parameters as pathological types, tumor size, invasiveness, and lymph-node metastasis. CONCLUSION: These data suggest that LOH at APC, MCC and DCC loci in esophageal carcinoma is, to certain extent, a common genetic alteration which might play a role in esophageal carcinogenesis. PMID- 11776788 TI - [Expression of heat shock protein 90 alpha and its effect on the growth of tumor in mice]. AB - OBJECTIVE: To study the effect of hsp90 alpha on the growth of tumor in mice and its mechanism. METHODS: Hsp90 alpha fusion protein was expressed in E. coli. DBA/2 mice were injected with purified fusion protein, then challenged with L1210 cells. The size of tumor was measured every other day. NK cell activity was detected by 51Cr release assay. RESULTS: The tumors grew faster while activity NK cell activity of mice was lower in the test mice than that in the control mice. CONCLUSION: The results suggest that the accelerated tumor growth is probably due to the formation of anti-hsp90 alpha antibody and decreased NK cell activity of mice treated with hsp90 alpha. PMID- 11776789 TI - [Apoptosis of ovarian carcinoma cell line induced by amiloride]. AB - OBJECTIVE: To investigate induction of apoptosis and its possible mechanism in amiloride-treated ovarian carcinoma cell line. METHODS: Morphological changes of apoptotic cells were investigated by light and fluorescence microscopy. DNA fragmentation was analysed by agarose gel electrophoresis. In addition, the number of hypodiploid cells (apoptotic cells) was quantitatively assessed by flow cytometry and intracellular pH was also analysed. RESULTS: Amiloride-treated ovarian carcinoma cells showed morphological characteristics of apoptosis. A ladder-like pattern of DNA fragmentation was demonstrated on agarose gel electrophoresis. Amiloride at 0.01-5 mumol/L could induce apoptosis in 18.7% 61.6% of ovarian carcinoma cells. The apoptosis-inducing effect of amiloride was dose- and time-dependent. In addition, amiloride induced intracellular acidification in a subpopulation of the treated cells. Furthermore, these isolated acidified cells revealed chromatin condensation as well as DNA degradation with characteristics of apoptosis. There was good correlation between apoptotic cells and acidic cells. CONCLUSION: Amiloride triggers apoptosis of ovarian carcinoma cells; intracellular acidification may be involved in the mechanism of apoptosis. PMID- 11776790 TI - [Transcatheter arterial chemoembolization combined with external radiation for primary liver cancer]. AB - OBJECTIVE: To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with external radiotherapy (RT) for primary liver cancer. METHODS: The effectiveness of combined therapy with TACE and RT (76 cases) and TACE therapy alone (68 cases) was prospectively nonrandomly studied. RESULTS: In TACE + RT group, the response rate (CR + PR) was 53.9%, and the 1-, 2 , 3-year survival rate was 71.6%, 49.0%, and 44.5%, respectively. In contrast, the response rate of TACE alone was 33.8%, and the 1-, 2-, 3-year survival rate was 51.8%, 17.3%, and 17.3%, respectively. The difference between these two groups was statistically significant (P < 0.05). Factors of prognostic significance in the TACE + RT group were tumor type, tumor cell thrombi in the portal system, number of TACE treatment and the use of gelform in embolization. CONCLUSION: TACE + RT is more effective than TACE therapy alone. Understanding of the prognostic factors is useful for selection and management of patients. PMID- 11776791 TI - [Expression of GST-pi gene in human esophageal carcinogenesis]. AB - OBJECTIVE: To investigate the possible role of GST-pi in esophageal carcinogenesis. METHODS: GST-pi expression at mRNA level was studied by in situ hybridization (ISH) and at protein level by immunohistochemistry (IHC). GST-pi expression of the esophagus in normal epithelial cells (NC), hyperplastic cells (HC), dysplastic cells (DC) from grade I to III, carcinoma in-situ (CIS) and invasive carcinoma (IC) was examined in the same esophageal cancer specimens (n = 48) which provided a model reflecting the process of esophageal carcinogenesis. RESULTS: The positive rate of IHC staining was 87.5% for NC, 95.3% for HC, 55.9% for DC (grade I: 73.9%, grade II: 47.4%, grade III: 41.2%), 36.4% for CIS and 45.8% for IC. The positive rate of GST-pi mRNA expression was 81.2% for NC, 94.4% for HC, 61.9% for DC (grade I: 76.5%, grade II: 61.5%, grade III: 41.7%), 44.4% for CIS and 83.3% for grade I IC, 30.0% for grade II IC and 0% for grade III IC. There was no statistically significant difference in GST-pi expression at the mRNA and the protein level. CONCLUSION: There is a decreasing tendency of GST-pi expression from dysplasia to CIS and IC. The decrease in GST-pi expression is an early event in esophageal carcinogenesis. PMID- 11776792 TI - [Study on factors influencing survival in patients with cancer of the esophagus after resection by Cox proportional hazard model]. AB - OBJECTIVE: To study the prognostic factors in patients with cancer of the esophagus after curative resection. METHODS: From 1985 to 1989 in our hospital, 1014 patients operated on for neoplasia of esophagus, who underwent a curative resection, and did not die within 30 days or during the hospital stay after operation, were included in this study. Thirteen possible factors influencing survival were selected. A multivariate analysis of these individual variables was performed using the cumulative survival rate by the computer's Cox proportional hazard model. RESULTS: The follow-up rate was 91.9% over 5 years. The over-all cumulative survival rate was 54.9% at 3 years, 45.9% at 5 years, and 39.3% at 10 years. The results showed that the major significant prognostic factors influencing survival of these patients were lymph node metastases, TNM stage, depth of invasion, location of tumor and histologic type (P < 0.0001). CONCLUSION: Lymph node metastasis is the most important prognostic factor for cancer of esophagus after curative resection. Lymphadenectomy along with esophagectomy is necessary to improve survival rate. PMID- 11776793 TI - [Perioperative use of peripherally inserted central catheter for parenteral nutrition in patients with abdominal malignancy]. AB - OBJECTIVE: To evaluate the use of peripherally inserted central catheter(PICC) in perioperative patients with abdominal malignancies for parenteral nutrition. METHODS: PICC was performed in 33 patients while subclavicular vein insertion in 30 patients for comparison in order to analyse prospectively the advantages and disadvanges of PICC. RESULTS: There was no difference in the rate of success of catheter placement and infection between PICC and the "subclavicular" insertion (P > 0.05), but PICC had significantly longer indwelling time than that of the "subclavicular" insertion (P < 0.05). There were less risks associated with PICC insertions, but the flow rate of was lower(p < 0.05). CONCLUSIONS: PICC can be widely used on account of its longer indwelling time, easy and safe insertion. PMID- 11776794 TI - [AFP mRNA expression in peripheral blood correlates with metastasis of hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the status of hematogenous spread of hepatocellular carcinoma (HCC) and the significance of peripheral blood AFP mRNA expression as a predictive marker for metastasis of HCC. METHODS: Peripheral blood samples were collected from 54 patients with HCC, 20 of whom had received interventional therapy before samples were collected, and from 30 subjects as control(10 cases with benign liver disease, 20 healthy donors). AFP cDNA was amplified from total RNA extracted from 5 ml whole blood by nested reverse transcription polymerase chain reaction(RT-PCR). RESULTS: Of the 54 HCC patients, 26(48.1%) patients had positive AFP mRNA, while AFP mRNA was detected in only 1 of the 10 patients with benign liver disorder and 1 of the 20 healthy subjects. In 16 HCC patients with intra- and extra-hepatic metastases, 13 (81.3%) were positive for AFP mRNA. In patients who did not yet have metastasis, 34.2% of them (13/38) gave positive AFP mRNA. The presence of AFP mRNA correlated with the stage of HCC and the presence of intrahepatic and/or extrahepatic metastasis, but did not correlate with the tumor size and the serum AFP level. There was no significant difference in AFP mRNA expression before and after surgical treatment or transcatheter arterial chemoembolization. CONCLUSION: AFP mRNA is a valuable marker for detecting hematogenous dissemination and metastasis of HCC. Systemic chemotherapy or immunotherapy is needed to prevent clinically overt metastasis and recurrence. PMID- 11776795 TI - [An approach to the cytologic diagnostic criteria of hepatocellular carcinoma by fine needle aspiration biopsy]. AB - OBJECTIVE: To identify useful cytologic features for diagnosis of hepatocellular carcinoma (HCC). METHODS: Fine needle aspiration(FNA) smears from 61 patients with proven HCC, 19 patients with metastatic tumors in the liver and 16 patients with non-neoplastic lesion of the liver were reviewed in order to detect the relevant cytologic changes associated with HCC. Step-wise logistic regression analysis was done to select useful cytologic features in discriminating HCC from metastatic tumors and non-neoplastic lesions of liver. RESULTS: Nine cytologic features observed were significantly associated with HCC: abundant tissue fragments(91.8%); trabecular pattern(91.8%); sinusoidal endothelial cells (47.5%); polygonal cells with centrally placed nuclei(82.0%); increased nuclear to cytoplasmic ratio(95.1%); large nucleoli(55.7%); bile granules(31.1%); cytoplasmic vacuoles(27.9%) and atypical naked hepatocyte nuclei(88.5%). In distinquishing HCC from metastatic tumors, polygonal cells with centrally placed nuclei, bile granules and trabecular pattern were useful cytologic features. Of the 61 patients with HCC, the logistic model correctly predicted 60(98.4%) as having HCC, while of the 19 patients with metastatic tumors, 18(94.7%) were correctly predicted. In distinquishing HCC from non-neoplastic liver disease, abundant tissue fragments, trebecular pattern, increased nuclear to cytoplasmic ratio and atypical naked hepatocyte nuclei were selected. When the four criteria were used, the sensitivity of diagnosing HCC was 100% and the specificity was 93.8%. CONCLUSION: Abundant tissue fragments, polygonal cells with centrally placed nuclei, increased nuclear to cytoplasmic ratio, trebecular pattern, atypical naked hepatocyte nuclei and bile granules are useful features for identifying HCC by FNA biopsy. PMID- 11776796 TI - [Evaluation of biliary CEA in the diagnosis of colorectal cancer with liver metastases]. AB - OBJECTIVE: To evaluate the clinical significance of biliary CEA for diagnosing colorectal cancer with liver metastases. METHODS: Three groups of patients were examined: 30 patients with benign disease in group A, 30 patients with colorectal cancer in group B, and 15 colorectal cancer patients with liver metastasis in group C. Fasting venous blood was drawn, and in the meatime, bile was collected by duodenal tube drainage before operation. CEA was detected with immunosorbent assay kit supplied by Boehringer. RESULTS: The serum level of CEA in group A, B, and C was (3.2 +/- 0.5) ng/ml, (11.7 +/- 2.4) ng/ml, and (14.8 +/- 3.5) ng/ml, respectively. The biliary CEA level was (23.7 +/- 8.6) ng/ml, (129.4 +/- 36) ng/ml, and (862 +/- 227) ng/ml, respectively. The difference in biliary CEA between group B and group C was statistically significant (P < 0.01). CONCLUSION: CEA level in the bile collected by duodenal drainage helps confirm liver metastasis in patients with colorectal cancer. PMID- 11776797 TI - [The value of "occult blood bead" in detection of upper digestive tract disorders with bleeding]. AB - OBJECTIVE: To evaluate the usefulness of "occult blood bead" (OBB) test in the screening of gastric and esophageal cancers. METHODS: In the study, subjects with upper gastro-intestinal (GI) symptoms received gastric OBB test before gastroscopic examination. OBB test was scored as +(-)+++ according to the intensity of reactions. The sensitivity, specificity, and likelihood ratio of OBB test were evaluated according to results of gastroscopic and/or pathological examination. RESULTS: Among 5,217 subjects, 2,403 showed positive OBB test (46.1%). In this series, 202 cases of malignant disorders were detected (gastric cancer in 155 and esophageal cancer in 47). There were 69 cancer cases among 1847 subjects presenting "+" OBB test, with a cancer detection rate of 3.7%. In 393 subjects presenting "++" OBB test, 28 were cancer (7.1%); while in 163 subjects presenting "+++" OBB test, 34 were diagnosed as gastric or esophageal cancer with a detection rate of 20.9%. The sensitivity of OBB test in detection of gastric and esophageal cancer was 0.65, the specificity was 0.55, likelihood ratio was 1.43 and the Youden Index was 0.2. CONCLUSION: OBB test provides a new, simple and non-invasive method for detection of upper digestive tract bleeding. For detection of upper GI carcinomas it presents a reasonable sensitivity and specificity in a group of subjects with upper GI symptoms. OBB test can be used as a prelimnary screening tool for gastric and esophageal cancer in asymptomatic general population. PMID- 11776798 TI - [CT findings of metastatic and primary neoplasms of the kidney: a comparative study]. AB - OBJECTIVE: To study CT findings of renal metastases and compare them with primary renal cell carcinoma. METHODS: CT features of eleven cases of renal metastases and one hundred cases of primary renal cell carcinoma confirmed by histopathology were studied and compared. The metastastic tumors arised from lung carcinoma in 6 cases, esophagus carcinoma in 2 cases and one in each of adrenal cortical carcinoma, testis seminoma and unknown primary tumor. RESULTS: Renal metastases accounted for 3.7% of all malignant tumors of the kidney. The ratio of renal metastases to second primary renal carcinoma was 1:1. On CT, the renal metastases appeared as diffusely invasive, ill-definded mass (63.6%), 18.2% of the neoplasms were multiple, without or less exophytic (81.8%) and without or with minimal enhancing on postcontrast scan (100%). The tumor invaded the pelvocalyceal system (72.7%). In contrast, the primary renal cell carcinomas were nodular, rounded or lobulated and more exophytic mass with well-defined border and regular contours (87.0%). Moderate to high enhancing postcontrast (80.7%) was observed with obvious necrosis (60.2%), foci of calcification (15.0%) and invasion of the renal vein and inferior vena cava (7.0%). CONCLUSION: Contrast-enhanced CT is helpful in the differential diagnosis of renal metastases from primary renal cell carcinoma. But for those showing single, more exophytic mass with well-defined border and intense enhancing postcontrast, the correct diagnosis depends on histopathology. PMID- 11776799 TI - [Clinical study of advanced nasopharyngeal carcinoma treated with radiotherapy combined with DDP and vindesine]. AB - OBJECTIVE: To evaluate the result of radiotherapy combined with chemotherapy for advanced nasopharyngeal carcinoma (NPC). METHODS: From August 1996 to October 1997, 64 cases of advanced NPC (stage N2-N3) patients were randomized to receive radiotherapy (RT) alone or RT combined with 2 cycles of chemeotherapy (CT) (cisplatin, vindesine). Thirty two patients were assigned to CT + RT, and 32 to RT alone. RESULTS: At 40 Gy of RT the response rate was 28.1% in RT group and 43.8% in CT + RT group. The response rate at 3 months after RT was 75.0% in RT group and 84.4% in CT + RT group (P < 0.05). The major toxic effects were gastrointestinal reaction, myelosuppession and alopecia. CONCLUSION: Chemotherapy with cisplatin and vindesine before and after radiotherapy increases the response rate of advanced NPC with lymph node metastases. PMID- 11776800 TI - [Short-term effect of navelbine on non-small cell lung cancer in 48 cases]. AB - OBJECTIVE: To evaluate effect of navelbine on non-small cell lung cancer (NSCLC). METHODS: Forty eight cases of cytologically and pathologically confirmed advanced NSCLC were treated with combined chemotherapy including navelbine as the cardinal drug from May, 1995 to January, 1988. They were randomly divided into two groups. One group of 20 cases was treated with NP regimen (NVB + PDD); the other group of 28 cases was treated with NI regimen (NVB + IFO). All patients received no previous treatment. RESULTS: There was no complete response in patients treated with either regimen. Partial response was observed in 8 of 20 NP-treated patients(40.0%) and in 12 of 28 NI-treated patients (42.8%). There was no statistical difference in response rate between these 2 groups of NSCLC patients. However, in both groups of patients, the therapeutic effect was better in adenocarcinoma than in sequamous-cell carcinoma patients. NP regimen seemed effective in the control of bone metastases and pains. Side effects were mainly myelo-suppression and digestive tract reaction. CONCLUSION: Combined chemotherapy including NVB is worthy of use in the treatment of advanced NSCLC especially for those with bone metastasis. PMID- 11776801 TI - [Symptomatic treatment versus combination chemotherapy in advanced non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the effects on survival of combination chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seventy patients with advanced NSCLC were pairingly divided into two equal groups: 35 patients who refused chemotherapy received symptomatic treatment; the other 35 patients received combined chemotherapy with mitomycin(8-10 mg/m2, dl), vindesine (3 mg/m2, dl, 8) cisplatin (20 mg/m2, dl-5), repeated every four weeks for 2-4 cycles and followed by oral administration of Ftorafur (FT-207) 200-300 mg tid, until recurrence or progression of disease. RESULTS: The overall median survival time in the chemotherapy group was 9 months, and 4.5 months in the symptomatically treated group. The one-year survival rate was 34.3% and 8.0% respectively. The major toxic effects of chemotherapy were gastrointestinal tract reactions and myelosuppression. CONCLUSION: Combination chemotherapy can prolong survival time in patients with advanced NSCLC. PMID- 11776802 TI - [Clinical significance of post-operative follow-up gastroscopy for patients with gastric cancer: a report of 986 cases]. AB - OBJECTIVE: To evaluate the clinical significance of postoperative follow-up gastroscopy in patients with gastric cancer. METHODS: Gastroscopy was performed in 986 patients with gastric cancer from 3 weeks to 21 years after operation. Each cases received gastroscopy 1 to 5 times in the follow-up period. RESULTS: Recurrent cancer was found in 75 cases, multiple primary malignant tumors in 4 cases and gastric stump cancer in 9 cases in the residual stomach. Functional disturbance of emptying after subtotal gastrectomy was found in 12 cases. Retention of gastric tube or silicon tube was found at the anastomotic stoma site in 9 cases. The other non-cancerous disorders included gastritis in 187 cases, residual non-absorbable sutures in 91 cases, metal staple in 4 cases, erosion in 51 cases, ulcer in 22 cases, polyposis in 38 cases and scar stenosis in 11 cases at anastomotic site. CONCLUSION: Routine postoperative gastroscopy check-up(s) is capable of early detecting cancer lesion and other non-cancer disorder in residual stomach. It helps increase survival rate and improve quality of life. PMID- 11776803 TI - [A clinical retrospective review of stage IB1 and IB2 cervical cancer]. AB - OBJECTIVE: To investigate the prognostic factors and treatment of cervical cancer in stage IB1 and IB2. METHODS: Three hundred fifty-six patients with stage IB cervical cancer were treated with redical hysterectomy. Seventy two patients received preoperative radiation (IB1 n = 39, IB2 n = 33), 83 patients received postoperative radiation (IB1 n = 61, IB2 n = 22), 11 patients received radiation before and after operation (IB1 n = 5, IB2 n = 6). RESULTS: Two hundred forty nine patients had been followed up for more than 5 years. The overall 5-year survival rate was significantly higher in patients in stage IB1 than in stage IB2. In patients with deep tumor invasion of the cervical matrix, the difference in 5-year survival was also significantly different between patients in stage IB1 and IB2. However, no significant difference was observed between the 2 groups of patients with positive nodes, nor was it related to tumor cell differentiation. Patients treated with surgery alone had similar 5-year survival rates but it was significantly higher in stage IB1 than in stage IB2 patients who received preoperative radiotherapy. Post-operative radiotherapy did not help survival in both groups of patients. CONCLUSION: The survival rate of cervical cancer in stage IB1 significantly differs from that in stage IB2. However, postoperative radiotherapy does not help improve survival of stage IB1 and IB2 patients with high risk factors. PMID- 11776804 TI - [In vitro cleavage action of c-erbB-2 oncogene-specific ribozyme]. AB - OBJECTIVE: To construct in vitro transcription vectors of genes of c-erbB-2 specific ribozyme and its substrate and to probe its in vitro cleavage action. METHODS: According to the computer design, a specific restriction site EcoR V was added to the 3' end of the ribozyme gene (RZ1). Then, the RZ1 gene and its substrate gene were cloned into the in vitro transcription vector pGEM3Zf(-) separately. The recombinants containing RZ1 gene were first screened by agrose ge1 electrophoresis through EcoR V digestion and was identified by automatic sequencing. The products of in vitro transcription were labeled with 32P. In vitro cleavage reaction was performed at 37 degrees C for 1 h under the presence of Mg++. The cleavage product was analyzed by polyacrilamide gel electrophoresis. After autoradiography, the cleavage rate was counted by image analysis. RESULTS: The recombinants containing the RZ1 gene were successfully selected by the EcoR V digestion and were designated as pGM3Z-RZ1. The automatic sequence analysis proved that the synthesized RZ1 gene was correct. The target gene was also cloned into the pGEM3Zf(-) under SP6 promoter. After in vitro transcription, the cleavage reaction was shown to have cut off 79.3% target RNA in 1 h. CONCLUSION: The c-erbB-2 oncogene-specific ribozyme has a high activity in vitro. It lays a foundation for the study of the therapeutic use of ribozyme in gene therapy of cancer. PMID- 11776805 TI - [Mortality of primary liver cancer in China from 1990 through 1992]. AB - OBJECTIVE: To study the geographical distribution and mortality of primary liver cancer (PLC) in China from 1990 through 1992. METHODS: A death survey among one tenth of Chinese population was conducted in 1990-1992 and the data on PLC mortality were analyzed. RESULTS: The crude mortality for PLC was 20.4 per 100,000 population (29.0 per 100,000 for males and 11.2 per 100,000 for females), accounted for 18.8% of the total cancer deaths in 1990-1992. In China, PLC mortality ranked second after stomach cancer. The age-standardized mortality rate (adjusted by the world population) of male Chinese was 33.7 per 100,000 which was 2. 2 times as high as that of male Japanese and 4.6 times as high as that of male Italian. The age-standardized rate of female Chinese was 12.3 per 100,000 which was 3.1 and 5.1 times as high compared to female Japanese and female Italian, respectively. PLC occurred in every age group but the mortality rate was highest in the age group of 30-44 years. The mortality was slightly higher in the rural than in the urban population. The cumulative death rate in the urban population was 3.5% for males and 1.2% for females, while that in the rural population was 4.1% for males and 1.6% for females. PLC showed geographical clustering along the south-east coast of China. CONCLUSION: To prevent primary liver cancer remains to be the major task of cancer control in China. PMID- 11776806 TI - [MAL gene is down-regulated substantially in human esophageal cancer]. AB - OBJECTIVE: To investigate the status of expression of MAL gene in human esophageal cancer. METHODS: Expression of MAL gene was analyzed by Northern blot and/or RT-PCR in 41 pairs of human esophageal cancer tissues and matched adjacent normal mucosa, and three human esophageal cancer cell lines EC109, EC8712 and EC9706. MAL gene was analyzed by PCR in the three esophageal cancer cell lines. RESULTS: MAL gene expression was down-regulated substantially or barely detectable in 93% (38/41) of human esophageal cancer tissues while expressed at high level in all matched adjacent normal esophageal mucosa. In all 3 human esophageal cancer cell lines, expression of MAL gene was not detectable. PCR analysis showed that the MAL gene fragment analyzed was intact in the three esophageal cancer cell lines. CONCLUSION: Down-regulation of MAL gene expression is of frequent occurrence in human esophageal cancer. PMID- 11776807 TI - [Apoptosis of human gastric cancer cells induced by bcl-2 antisense oligodeoxynucleotides]. AB - OBJECTIVE: To study the regulation of bcl-2 gene expression and induction of apoptosis by bcl-2 antisense oligodeoxynucleotides (AS-ODN) on human gastric cancer cell line BGC-823 in vitro. METHODS: Two bcl-2 AS-ODNs were synthesized, one covering the initiation sequence of translation of bcl-2 mRNA (AS-ODN1) and the other covering the protein coding region (AS-ODN2). BGC-823 cells in logarithmic phase of growth were cultured in the presence of free or liposome (DOTAP)-encapsulated AS-ODN. Cell growth was assessed by MTT method. The expression of bcl-2 at mRNA and protein levels was examined by RT-PCR and flow cytometry, respectively. Electron microscopy and flow cytometry were used to demonstrate apoptotic changes in AS-ODN-treated cells. RESULTS: Both AS-ODNs inhibited proliferation of BGC-823 cells. The inhibitory activity of AS-ODN2 was stronger than that of AS-ODN1. AS-ODNs encapsulated in liposome led to more marked inhibition of cell growth than free AS-ODNs. Both AS-ODNs reduced bcl-2 expression of BGC-823 cells at mRNA and protein levels. Apoptosis of BGC-823 cells were demonstrated by the appearance of apoptotic bodies, chromatin condensation and pre-G1 peak on flow cytometric analysis. CONCLUSION: Antisense oligodeoxynucleotide of bcl-2 decreases bcl-2 gene expression and induces apoptosis of human gastric cancer cells in vitro. PMID- 11776808 TI - [Changes in [Ca2+]i and IP3 levels in the process of cisplatin-induced apoptosis of gastric carcinoma]. AB - OBJECTIVE: To study the change and significance of intracellular-free calcium levels ([Ca2+]i) and inositol 1, 4, 5-trisphosphate (IP3) levels in the process of gastric carcinoma cell apoptosis induced by cisplatin. METHODS: Apoptosis induced by cisplatin in gastric carcinoma BGC823 cell was investigated by light and electronmicroscopy, agarose gel electrophoresis and flow cytometry. [Ca2+]i was determined by Fura-2 fluorescin load technic, IP3 was determined by competitive protein binding method. RESULTS: When BGC823 cells were treated with cisplatin (2 micrograms/ml) for 24 hours changes appeared typical of apoptosis. [Ca2+]i and IP3 were significantly increased, especially at the initial stage of apoptosis. However, from 2 to 24 hours after cisplatin treatment, IP3 levels progressively decreased, being significantly lower than those of the untreated controls. CONCLUSION: In the process of cisplatin induced apoptosis of gastric carcinoma cells, [Ca2+]i and IP3 levels are up-regulated at the very initial stage but down-regulated from 2 hours afterwards. PMID- 11776809 TI - [Glutathione synthesis inhibitor enhances arsenic trioxide-induced apoptosis]. AB - OBJECTIVE: To illustrate the possible role of thiols (SH-groups) in arsenic trioxide (As2O3)-induced apoptosis. METHODS: Leukemia (NB4, HL60, U937) and lymphoma (Jurkat and Namalwa) cell lines were treated with As2O3 together with buthionine sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase. The mitochondrial transmembrane potentials (delta psi m) and the percentage of cells in apoptosis were measured by means of flow cytometry. RESULTS: One mmol/L BSO significantly enhanced As2O3-induced delta psi m collapse and apoptosis in NB4 cells. One mumol/L As2O3 did not induce the delta psi m collapse and apoptosis in Namalwa, HL60, U937 and Jurkat cells, while these effects were induced significantly by the co-treatment of 1 mumol/L As2O3 and 1 mmol/L BSO. CONCLUSION: Thiols are important chemosensors of As2O3-induced delta psi m collapse and apoptosis. PMID- 11776810 TI - [Effect of beta-carotene on mouse transplantable mammary cancer MA737]. AB - OBJECTIVE: To study the effect of beta-carotene (BC) on the growth of MA737 in TA II mice. METHODS: BC (250 mg/kg) dissolved in vegetable oil was given per os by gavage once every other day. Mice were treated with BC alone or in combination with chemotherapy (CMF protocol). Control mice were given solvent vehicle. Tumor volume and survival period of the treated and control mice were recorded. RESULTS: In mice treated with BC alone, the growth of the tumor was retarded, but the tumor inhibitory effect was more marked in mice treated with BC + CMF (growth inhibition rate: 49.1% versus 60.5%). The therapeutic effect of combined use of BC and CMF was only slightly better than that of CMF alone. However, BC helped alleviate toxic side effects of the chemotherapeutic drugs so that the survival period was significantly prolonged in the BC + CMF treated mice. Long term treatment with beta-carotene was without side effect. CONCLUSION: beta-carotene inhibits tumor growth, prolongs survival and alleviates toxic side effects of chemotherapy in a mouse mammary cancer model. PMID- 11776811 TI - [Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer]. AB - OBJECTIVE: To study the expression of p27kip1 in breast cancer in relation to biological behavior and prognosis. METHODS: p27kip1 expression at protein level was determined by immunohistochemistry technique in 181 patients with breast cancer. In addition, p27WAF1/CIP1, p53 and mdm2 were examined in 106 cases of this series. Data about apoptotic index, bcl-2 and bax protein expression were available in the other 91 patients. RESULTS: Of the 181 patients, p27kip1 expression was low in 121 (66.9%) and high in 60 (33.1%), respectively. p27kip1 expression level was correlated with histological grade, tumor size, axillary lymph node status, post-operative recurrence, invasion and metastasis. It was also correlated with bcl-2, bax, p53, p21WAF1/CIP1, and mdm2 expression levels. Univariate analysis demonstrated better disease-free survival in patients with higher p27kip1 expression than in those with lower expression. However, by Cox multivariate analysis, p27kip1 expression level was not found to be of independent prognostic significance. CONCLUSION: As an inhibitor of cyclin dependent kinase, p27kip1 favors prognosis of human breast cancer not only by arresting cell cycle in G1 phase but also inducing cancer cell apoptosis. PMID- 11776812 TI - [Inquiring the causes of recurrence of hepatocellular carcinoma after surgical resection]. AB - OBJECTIVE: To analyze the causes of recurrence of hepatocellular carcinoma (HCC) after resection according to pathologic findings of the resected primary tumor and angiographic features of the recurrent tumor. METHODS: In this series, 142 cases with recurrent HCC were analyzed with respect to (1) size, number, gross and histologic findings of the primary tumor, (2) time when recurrence occurred, (3) size, number, blood supply, staining property of, and deposition of lipiodol oil in the recurrent tumor. Following angiography, arterial embolization was performed. RESULTS: In 101 of the 142(71.1%) cases, the primary tumor was > 5 cm in diameter, and in 41 cases (28.9%) it was < 5 cm. In 67.7% of the cases, the capsule of the primary tumor was incomplete or absent. In 47 cases (33.1%), satellite tumor nodules were seen during operation but they were seen on pathologic sections in 94 cases (66.2%). Tumor thrombus was present in the portal vein in 26 (18.3%) and 121 cases (85.2%) during operation and on pathologic examination, respectively. In the majority of the cases (99/142), recurrence occurred within 6 months after operation. The recurrent foci consisted of multiple tumor nodules of < 5 cm in 68.3% of the cases. On angiography, the recurrent tumors were rich in blood supply with good deposition of lipiodol. CONCLUSION: Recurrence is apt to occur in HCC patients with large (> 5 cm) primary tumor which has incomplete or no capsule, satellite tumor nodules and portal vein tumor thrombus. It is suggested to perform angiography 1-2 months after surgery to detect early recurrence and, if confirmed, the patients can be treated by transcatheter arterial chemo-embolization. PMID- 11776813 TI - [Clinico-pathological characteristics and prognosis of thymoma: an analysis of 159 cases]. AB - OBJECTIVE: To investigate the clinicopathologic features of thymoma and assess prognostic factors. METHODS: Data of 159 patients operated for thymoma were collected. A retrospective analysis was performed, through comparison of survival rate computed by the actuarial method and rate of recurrence and metastasis. RESULTS: (1) The 3-, 5-, and 10-year survival rate was 78.9%, 63.7% and 46.3%, respectively. All patients treated by subtotal thymoma resection with postoperative radiotherapy survived more than 3 years. (2) Patient's age, location and image density of tumor play important role in differential diagnosis. (3) Tumors with epithelial predominance were more frequently seen in late stage than those of other histologic types(P < 0.01). (4) The prognosis of patients whose tumors had incomplete or no capsule was poor as compared to that of stage I tumor (P < 0.05). (5) According to multivariate analysis, the most important prognostic variables included completeness of resection (OR = 2.10) and clinicopathologic stage (OR = 1.73). Myasthenic crisis was the most important factor influencing operative death. Sex, symptoms and histologic classification did not influence prognosis. (6) Recurrence and metastasis occurred in all stages, but more frequent in the later stages of the disease. CONCLUSION: Complete resection helps decrease recurrence of thymoma. Prognosis of patients receiving palliative resection of thymoma may be improved by postoperative radiotherapy. PMID- 11776814 TI - [Long-term effect of treating patients with precancerous lesions of the esophagus]. AB - OBJECTIVE: To report long term therapeutic effect in patients with esophageal pre cancerous lesions in high-risk area of esophageal cancer. METHODS: The therapeutic trial enrolled 2,531 cases of severe dysplasia and 3,393 cases of mild dysplasia. A 2-arm randomized, placebo-controlled design was used in which the participants received Zeng Sheng Ping (ZSP, an herbal composite), retinamide or placebo for cases with severe dysplasia and riboflavin or placebo for those with mild dysplasia. RESULTS: Treatment with ZSP and retinamide decreased malignant transformation rate of severe dysplasia by 52.2% and 43.2%, respectively after 5 years of treatment. When the treatment had been discontinued for 4 years, the rate of malignat transformation was decreased by 42.1% and 38.2% respectively, which remained significantly higher than that of the placebo treated control. Riboflavin treatment was continued for 9 years. At the end of 5 year medication, the malignant transformation rate decreased by 34.8%, which was not significantly different from that of the placebo control. When the treatment was continued up to 9 years, the rate was further decreased to 37.0%, which became statistically significant. CONCLUSION: ZSP, retinamide and riboflavin treatment can effectively prevent esophageal dysplasia from transforming into carcinoma. PMID- 11776815 TI - [Telomerase activity in breast carcinoma]. AB - OBJECTIVE: To investigate the significance of telomerase activity in breast carcinoma with respect to axillary lymph node status. METHODS: Telomerase activity was analyzed in 88 breast carcinomas specimens and 16 benign breast lesions, using PCR-based telomeric repeat amplification protocol (TRAP) assay. RESULTS: Telomerase activity was detected in 75 (85.2%) of 88 breast carcinomas (including three breast carcinomas in situ which were all positive for telomerase activity), whereas in benign breast lesions analyzed only 2 (12.5%) of 16 cases were positive (P < 0.001). Besides, telomerase activity was significantly higher in node-positive breast carcinomas (93.2%) than in node-negative ones (77.3%, P < 0.05). CONCLUSION: The results suggest that telomerase activation plays an important role during breast carcinoma progression. It may serve as an early marker of breast carcinoma. PMID- 11776816 TI - [Correlations between invasion of gastric cancer to serosal layer and other relevant factors]. AB - OBJECTIVE: To study correlations between invasion of stomach cancer to serosal layer and such factors as size and type of tumor, depth of ulcer, gastric wall contraction, etc. METHODS: Gastric cancer specimens from 150 patients admitted to the hospital in March 1993 through March 1997 were examined. RESULTS: The frequency of tumor invasion to the serosa in gastric cancer of Borrmann type I, II, III and IV was 8.3%, 23.4%, 32.9% and 76.2%, respectively. The frequency of serosal involvement was 13.6% in tumors with a diameter < or = 3.0 cm which was significantly less frequent than in tumors with a diameter > 3.0 cm. The frequency of serosal involvement increased with the increase in depth of ulcer and with spastic contraction of gastric wall as observed in pre-operative barium meal examination. That of serosal involvement varied with degree of differentiation of the tumor, being much lower in well- and moderately well differentiated adenocarcinomas (10.3%) than in poorly differentiated ones (62.8%). The serosa was frequently invaded by mucinous adenocarcinoma (42.9) and signet cell carcinoma (83.3%). CONCLUSION: Invasion of gastric cancer to serosal layer correlates, to various extents, with the tumor size and type, status of cell differentiation, and depth of ulcer. PMID- 11776817 TI - [Study of recurrence and metastasis after radical resection of carcinoma of the lung]. AB - OBJECTIVE: To study the characteristics of recurrence and metastasis following radical resection of carcinoma of the lung. METHODS: A total of 1,229 cases of radically resected lung cancer was statistically analyzed using STATA software. The survival rate was estimated using life table method. Comparisons of survival in each group were made according to the log rank test. The differences in rate between groups was assessed by chi 2 test. RESULTS: Recurrence rate was found higher in squamous-cell carcinoma than in adenocarcinoma. It was also higher in sleeve resection and partial resection than in other resection modes (P < 0.05). The rate of lymph node metastasis was higher in adenocarcinomas than in squamous cell carcinoma (P < 0.05). Lung, bone, brain, liver, subcutis, and adrenal glands were the common resorts of metastasis, in decreasing order of frequency. Metastatic rate was the lowest in squamous-cell carcinoma. Active therapy can still improve the survival even when recurrence and metastasis occurred. CONCLUSION: It is recommended to avoid partial resection for the invaded adjacent lobe whenever patient's condition can stand multilobectomy. It is necessary to assure resection margin length when sleeve resection is performed in order to reduce recurrence. Active therapy can improve survival of patients with recurrence and metastasis. PMID- 11776818 TI - [Usefulness of CYFRA21-1 as a tumor marker of non-small-cell lung cancer]. AB - OBJECTIVE: To evaluate the clinical usefulness of CYFRA21-1 as a serum tumor marker in diagnosis, evaluation of clinical status and prognosis of patients with non-small-cell lung cancer (NSCLC). METHODS: CYFRA21-1 in 126 serum samples of NSCLC patients was measured by radioimmunoassay. Of the 126 samples, 71 were collected before treatment, 29 at two weeks after operation, and 26 after 15-18 months follow-up. RESULTS: CYFRA21-1 was positive in 49.3% of the NSCLC patients who had not received any treatment. The positive rate was 69.2% for squamous-cell carcinoma, and 25.0% for adenocarcinoma. The serum level of CYFRA21-1 was significantly higher in squamous-cell carcinoma than in adenocarcinoma (P < 0.0001). The serum level of CYFRA21-1 well correlated and increased with TNM staging (P = 0.0001). The level decreased significantly within two weeks after surgical operation in 29 cases (P = 0.0005). On follow up for 15-18 months, no change in CYFRA21-1 level was observed in 16 patients whose disease was stable, while there was significant increase in 10 patients with progressive disease. CONCLUSION: CYFRA21-1 is a soluble fragment of cytokeratin 19 in serum of patients with NSCLC. It can be used as a useful tumor marker of NSCLC. PMID- 11776819 TI - [Prognostic value of cell proliferation and apoptosis in uterine cervical cancer treated with radiation]. AB - OBJECTIVE: To study the prognostic value of cell proliferation and apoptosis in cervical cancer patients treated with radiation. METHODS: A retrospective study was done in 40 radiotherapy-uncontrolled cases of squamous-cell carcinoma of the cervix uteri and an equal number of cases, matched in age, clinical stage, tumor size and histologic grade, which had been cured by radiotherapy. Cell proliferation was judged by the proliferating cell nuclear antigen (PCNA) positively stained cell number x intensity of staining, and number of cells in mitosis per 10 high-power microscopic fields (HPF). Apoptotic cells were identified by TUNEL method and the result was expressed as the number of cells undergone apoptosis per 10 HPF. RESULTS: The average level of PCNA expression was 5.38 +/- 3.21 in the cured patients and 7.50 +/- 3.16 in the radiotherapy uncontrolled patients (P < 0.01). The number of mitotic cells/10 HPF was 6.33 +/- 5.15 in the cured patients and 11.33 +/- 7.50 in the uncontrolled patients (P < 0.001). The number of apoptotic cells/10 HPF was 20.90 +/- 8.19 in the cured patients and 27.13 +/- 17.28 in the uncontrolled patients (P < 0.05). The ratio of number of apoptotic cells to that of mitotic cells (A/M) was 4.97 +/- 3.31 in the cured and 3.36 +/- 2.83 in the uncontrolled (P < 0.05). CONCLUSION: In cervical cancer, PCNA expression, the number of cells in mitosis and that of cells in apoptosis are significantly increased while the A/M ratio is significantly decreased in radiotherapy-uncontrolled patients compared to those of patients cured by radiotherapy. These parameters may be of value of predict response to radiotherapy and prognosis of patients with cervical cancer. PMID- 11776820 TI - [Significance of TNM clasification in prognostic evaluation of hepatocelluar carcinoma following surgical resection]. AB - OBJECTIVE: To investigate correlation between TNM classification of HCC and local regional cancer-free survival time after hepatectomy. METHODS: A retrospective survey was carried out in 1,725 cases with hepatocellular carcinoma (HCC) receiving radical or relatively radical operation from Jan. 1, 1990 through Dec. 31, 1995. The follow-up rate was 84.46%. The factors under consideration were analysed using Cox proportional hazards survival model and Kaplan-Meier estimation. RESULTS: Univariate analysis showed that 13 clinical and pathologic factors, including clinical stage, age, portalvein tumor thrombus, tumor number found before and/or during operation, radical or relatively radical resection, size of tumor, growing pattern, encapsulation of tumor, daughter nodules (including microscopic nodules), vascular invasion, TNM stage, AFP level after hepatectomy and so on, might all influence local-regional cancer-free survival time. Multivariate analysis revealed four significant prognostic factors: tumor number found before operation, tumor size, daughter nodules and vascular invasion. These four factors were encompassed in TNM staging. By Kaplan-Meier estimation, tumor-free survival rate at 0.5, 1, 3, and 5 years was as follows: at stage I 90.7%, 79.1%, 45.8%, 24.6%; at stage II 86.6%, 75.5%, 51.8%, 38.4%; at stage III 62.6%, 41.5%, 20.6%, 15.9; at stage IV a 33.0%, 18.6%, 8.0%, 5.3%; at stage IVb 42.3%, 35.3%. The mean tumor-free survival time of stage I to IVb was 34.36, 38.25, 10.01, 4.06 and 4.26 months, respectively. There was no significant difference in tumor-free survival rate btween stage I and II. CONCLUSION: TNM stage is one of the most significant prognostic factors determining tumor-free survival after HCC resection. PMID- 11776821 TI - [Preoperative staging of patients with primary ovarian carcinoma by CT and MRI]. AB - OBJECTIVE: To investigate values and limitations of CT and MRI applied in staging of patients with primary ovarian carcinoma (POC). METHODS: Forty two patients with POC proven by radical surgery, laparotomy, and postoperative pathology were studied. In comparison to surgical and pathological findings, sensitivity, specificity, and accuracy of CT, MRI and CT plus MRI were calculated. Staging by the three imaging methods was obtained according to FIGO's classification. RESULTS: CT and MRI showed higher accuracy in evaluation of invasion to uterus (89.5% and 94.7%) and disease of Douglas pouch (94.7% and 97.4%). CT was to some extent superior to MRI in assessing ipsilateral or bilateral tumor and lesions related to peritoneal seeding; MRI, however, had better capability of diagnosing invasion to ovarian capsule, pelvic organs excluding bowel, nodules in Douglas pouch, and metastasis to lymph nodes. The overall accuracy of staging by CT, MRI, and CT plus MRI was 73.7%, 68.4%, and 70.6%, respectively (P > 0.05). CONCLUSION: CT and MRI are useful imaging modalities in staging of POC, but low sensitivity for detecting involvement in some anatomic regions needs to be improved. PMID- 11776822 TI - [Therapeutic results of second-look laporatomy with extensive dissection of retroperitoneal lymph nodes in ovarian cancer patients]. AB - OBJECTIVE: To evaluate retrospectively the results of extensive lymphadenectomy during second-look laparotomy in patients with ovarian cancer. METHODS: An total of 63 patients with ovarian malignancies received second-look laparotomy (SLL). Retroperitoneal lymph nodes, including para-aortic nodes below the level of left renal vein and pelvic nodes were extensively dissected. RESULTS: Of the 63 patients, residual tumor was found in 24 (38.1%) on SLL. The frequency of residual tumor was positively correlated with the clinical stage and with the amount of tumor left after initial debulking but not with the degree of differentiation of tumor cells. Lymph node metastasis was pathologically confirmed in 19 cases (30.2%), in which no residual tumor was found in 8 patients. Tumor recurred in only 4 of the 39 patients (10.3%) with negative SLL. The overall 3- and 5-year survival rate was 75.4% and 68.3%, respectively. CONCLUSION: Extensive retroperitoneal lymph node dissection is recommended during SLL. It favors a decrease in recurrence rate in ovarian cancer patients negative on SLL. PMID- 11776823 TI - [Thyroid squamous-cell carcinoma showing thymus-like element (CASTLE): a report of eight cases]. AB - OBJECTIVE: To report 8 cases of squamous-cell carcinoma showing thymus-like element (CASTLE) of the thyroid. METHODS: Clinical data and pathological sections were retrospectively reviewed. RESULTS: CASTLE of the thyroid differed from ordinary squamous-cell carcinoma (SCC) in that it not only presented typical squamous pattern of differentiation, but also admixed with thymic architecture, such as Hassall's corpuscles, lymphoepithelial-like structure and mature lymphocyte infiltration in the stroma. CASTLE of the thyroid and much better prognosis than that of the ordinary SCC of the thyroid with a median survival time of 10.5 year. Histogenesis of CASTLE was discussed. CONCLUSION: Thyroid CASTLE is of rare occurrence. It should be distinguished from SCC of thyroid in order to treat such patients adequately. PMID- 11776824 TI - [Local resection of carcinoma of ampulla of Vater: an analysis of 52 cases]. AB - OBJECTIVE: To study the therapeutic results of patients with carcinoma of ampulla Vater treated by local tumor resection. METHODS: Four cases of carcinoma of ampulla of Vater treated in our hospital by local tumor resection and 48 cases reported in Chinese medical literature in 1992-1997 were analyzed. RESULTS: A total of 52 cases was collected who received local resection of carcinoma of ampulla of Vater. The operative mortality was 3.8% and the morbidity was 9.6%. Recurreuce occurred in 12 cases, of whom 3 had poorly differentiated adenocarcinoma, 7 had their tumor incompletely resected with tumor left at the cutting edge and one had local invasion. In 8 month to 4 years, 19 cases died. Thirty two cases survived for 7 months to 8 years after operation. CONCLUSION: The prognosis of local resection is related not only to tumor size, extent of invasion, metastasis to lymph node, but also to pathologic types and differentiation. It is a treatment of choice for early carcinoma of ampulla of Vater in patients who are at high-risk due to old age, poor general condition or severe concurrent diseases. PMID- 11776825 TI - [Effect of ATP on malignant phenotype of a human gastric cancer cell line]. AB - OBJECTIVE: To study the effect of ATP on proliferation and differentiation of a human gastric cancer cell line. METHODS: M17, a subclone of human gastric cancer cell line MGC-803, was treated in vitro with ATP(0.23 mg/ml). After 48 hr, the following parameters were examined. (1) Proliferation of cells by daily cell counting. (2) Microvilli of the cells were observed by scanning EM. (3) Gap junction intercellular communication was examined by mechanical scraping and Lucifer dye transfer. (4) Microfilament of the cytoskeleton was studied with fluorescin-labeled phalloidin. (5) Vinculin adhesion plague was stained immunocytochemically with monoclonal antibodies. RESULTS: ATP significantly inhibited the in vitro growth of M17 cells. The ATP-treated M17 cells showed disappearance of microvilli on the cell surface, increased gap junction intercellular communication, improved organization of microfilament bundles and reappearance of vinculin adhesion plagues. CONCLUSION: ATP not only inhibits proliferation but also induces differentiation of a human gastric cancer cell line with reversion from malignant toward normal phenotype. The parameters examined could serve as useful biomarkers of human gastric cancer. PMID- 11776826 TI - [Alterations of cell apoptosis and proliferation during transformation of a human bronchial epithelial cell line]. AB - OBJECTIVE: To investigate the alterations of cell apoptosis and proliferation and its mechanism during transformation of a human bronchial epithelial cell line Y. METHODS: Terminal deoxyribonucleotidyl transferase in situ labelling, BrdU incorporation, Western blotting and fluorescence in situ hybridization were used in the study. RESULTS: During serial passages of the immortalized human bronchial epithelial cell line Y, some phenotypic alterations, such as higher colony forming efficiency in soft agar, resistance to serum-induced differentiation and low dependence on EGF were observed. The increase in cell proliferation and decrease in cisplatinum-induced apoptosis and the enhanced protein expression of Bcl-2, MDM2, PCNA and Cyclin D1 were found in the late passages of the cell line. The chromosomes of Y cells were diploid at the early passages, but became aneuploid in the late passages. CONCLUSION: In addition to the increase in cell proliferation, inhibition of apoptosis might also contribute to the cytogenetic abnormality and the transformation of human bronchial epithelial cells. PMID- 11776827 TI - [Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells]. AB - OBJECTIVE: To investigate the effects of genistein on cancer invasion and associated cellular characteristics and explore the possibility of developing protein tyrosine kinase inhibitors as anti-metastasis drugs. METHODS: HT1080 human fibrosarcoma cells were exposed to 20 mumol/L or 40 mumol/L genistein for 3 days. The abilities of the genistein-treated cells to invade through reconstituted matrigel or migrate through polycarbonate filters in transwell chambers were then investigated. Northern blot and laser densitometry were used to estimate the relative mRNA amounts of MMP-2, MMP-9 and TIMP-1 in the cells. RESULTS: The ability of the genistein-treated HT1080 cells to invade the reconstituted basement membrane was decreased significantly (P < 0.01). In consistent with the lowered invasive potential, migration rates of the drug treated cells decreased dramatically. genistein did not, however, significantly affect attachment of HT1080 cells on fibronectin, laminin or Matrigel. Though exposure to genistein led to a small increase in MMP-2 and MMP-9 gene expression, a much greater increase in the amount of TIMP-1 mRNA was observed. Imbalanced enhancement of gene expression between matrix metalloproteinases and their inhibitors in favor of the latter may imply that matrix degradation is impaired in the genistein-treated cells. CONCLUSION: Genistein suppresses invasion of HT1080 cells at relatively low concentrations. genistein and other protein tyrosine kinase inhibitors might be valuable candidate drugs for the treatment of invasion and metastasis of cancer. PMID- 11776828 TI - [p16 gene suppresses growth of human esophageal carcinoma cells]. AB - OBJECTIVE: To explore the effect of p16 gene on the growth inhibition of esophageal carcinoma cell line NEC. METHODS: The full length of wild-type p16 cDNA was transfected into the esophageal carcinoma cell line of human fetus induced by N-methyl-N-benzylnitrosamine (NMBzA). In these esophageal carcinoma cell, p16 gene was homozygously deleted. RESULTS: Expression of exogenous p16 gene in NEC cells was identified by dot blot and Western blot analyses. The growth rate of NEC transfected with p16 gene (NEC-p16) was markedly suppressed. Colony formation in soft agar was also decreased significantly. Cell cycle analysis by flow cytometry showed that the number of cells in G1-G0 phase of NEC p16 cells was significantly increased while cells in S and G2 + M phase was decreased compared to that of the control NEC cells. CONCLUSION: Transduction of wild type p16 gene into p16 gene-depleted esophageal cancer cells can restore its suppressive effect on cell growth by arrest of cell cycle at G1 phase. PMID- 11776829 TI - [RAB5A, a gene possibly related to metastasis of human carcinoma of the lung and stomach]. AB - OBJECTIVE: To study and isolate tumor metastasis-related genes, and to explore the molecular basis of metastasis of lung and gastric carcinoma. METHODS: Using mRNA differential display technique, cDNA cloning and sequencing, RT-PCR, Northern blot and immunocytochemical methods, genes differentially expressed between human lung adenocarcinoma cell lines AGZY83-a and Anip973 were detected. Anip973 was isolated from AGZY83-a with much higher metastatic potential than the parent line. RESULTS: There were significant differences in gene expression between the two cell lines. RAB5A was one of the genes differentially expressed in Anip973 cells. Its gene product is a GTP-binding protein. Paraffin sections of 33 lung carcinoma and 47 gastric carcinoma specimens were examined immunohistochemically. Expression of RAB5A was positive in 87.9% of NSCLC and 91.5% of gastric cancer specimens examined (P < 0.05), and correlated with their metastatic potential and differentiation degree of gastric carcinoma. CONCLUSION: RAB5A is possibly a metastasis-related gene. PMID- 11776830 TI - [A novel human DNA sequence with tumor metastasis suppressive activity]. AB - OBJECTIVE: To isolate human tumor metastasis suppressive DNA sequence and to study the molecular mechanisms regulating tumor metastasis. METHODS: A mouse lung adenocarcinoma cell clone 12 derived from its parent cell line LM2, which had been transduced with normal human genomic DNA, was previously reported. Compared with LM2, the metastatic potential of clone 12 was very much decreased. Clone 12 was used in this study to amplify the human DNA fragments by Inter Alu PCR technique. The human DNA fragments obtained were then transfected into LM2 cells and their malignant phenotype was observed in vitro and in vivo, and compared with that of the untransfected LM2 cells. RESULTS: Three human DNA fragments of 700, 500 and 300 bp were isolated. DNA sequencing revealed that the 700 bp fragment does not show homology with hitherto reported genes and was accepted by the GenBank (pt 712 U67835). In vitro proliferation and colony formation in soft agar of the 700 bp fragment-transfected LM2 cells were significantly inhibited as compared to the untransfected LM2 cells. Upon subcutaneous inoculation to syngeneic T739 mice, the 700 bp-transfected LM2 cells grew more slowly and smaller tumors developed compared to the un-transfected ones. Moreover, lung metastasis was not found in 6 of 10 mice inoculated with the 700 bp-transfected LM2 cells, while it was found in 9 of 10 mice inoculated with the un-transfected LM2 cells. The difference was statistically significant (P < 0.001). The frequency of lymph node metastasis was also statistically different between the 2 groups of mice. CONCLUSION: The newly isolated 700 bp human DNA fragment may be a metastasis suppressor gene of malignant tumor. PMID- 11776831 TI - [Protective effect of mutant dihydrofolate reductase gene on human peripheral blood CD34+ cells against methotrexate]. AB - OBJECTIVE: To examine if human peripheral blood hematopoietic progenitor cells transduced with mutant dihydrofolate reductase(mDHFR) gene may increase their resistance to metrotrexate(MTX). METHODS: After enrichment with a high-gradient magnetic cell sorting system(MACS), the peripheral blood CD34+ cells were transfected with supernatant of retrovirus containing human mDHFR cDNA. Colony formation of hematopoietic progenitor cells was utilized to evaluate mDHFR conferred resistance to MTX. The number of colonies formed from every 500 cells seeded was counted and expressed as the percentage of colony formation. RESULTS: After the mD-HFR-transduced CD34+ cells had been screened in vitro in medium containing 20 nmol.L-1 MTX for 14 days, the percentage of colony formation of mDHFR cDNA-transduced and of mock-transduced CD34+ cells was 29.4% and 16.3%, respectively (P < 0.01). The resistance to MTX was increased twofold. CONCLUSION: Transduction of mDHFR gene could confer the resistance of human hematopoietic progenitor cells to MTX toxicity. PMID- 11776832 TI - [Effect of cefodizime on cellular immunity in patients with lung cancer]. AB - OBJECTIVE: To study the enhancing effect of cefodizime on cellular immunity of patients with lung cancer. METHODS: The parameters of cellular immunity in blood and pulmonary alveoli were investigated in 45 patients with lung cancer complicated with lower respiratory tract infection (LRTI) and 10 non-cancer patients with LRTI. Nitroblue tetrazolium (NBT) reaction of polymorphonuclear neutrophils (PMN), the percentage of natural killer (NK) cells, and that of CD4+ cells, ratio of CD4+/CD8+ in peripheral blood, OD value of alveolar macrophages phagocyting neutral red, and IL-1 beta (ng/L) in broncho-alveolar lavage flind (BALF) were determined. RESULTS: The parameters examined in cancer patients with LRTI were significantly improved after cefodizime treatment, approaching to those seen in non-cancer patients with LRTI. The therapeutic results were better in patients treated with cifodizime than in patients treated with ceftriaxonum. CONCLUSION: Cefodizime is a better choice of antibiotic for the treatment of lung cancer complicated with lower respiratory tract infection. Its enhancing effect on systemic and local immune functions plays a role. PMID- 11776833 TI - [Expression of multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in human rectal carcinomas and its clinical significance]. AB - OBJECTIVE: To investigate the expression and clinical significance of multidrug resistance-associated protein(MRP) and lung resistance protein(LRP) in rectal carcinoma. METHODS: Fiftyseven paraffin embeded primary rectal carcinoma specimens were examined by immunohistochemical staining. RESULTS: Of the 57 tumour specimens examined, 28(49.1%) and 24(42.1%) were positively immunostaned for MRP and LRP, respectively. Co-expression of the two proteins was observed in 10(17.5%) specimens. Positive immunostaning of either of the two proteins was not correlated with cell differentiation and Dukes stage (P > 0.05). Patients with MRP-positive tumours had shorter survival than MRP-negative patients (P < 0.05). No such correlation was found for LRP expression, nor was found between MRP and LRP expression. CONCLUSION: Positive MRP expression in rectal carcinoma appears to be an independant factor of prognostic significance. To examine its expression may help guide rational comprehensive therapy of rectal carcinoma. PMID- 11776834 TI - [Expression and significance of urokinase-type plasminogen activator in breast cancer]. AB - OBJECTIVE: To study the expression and clinical significance of urokinase-type plasminogen activator (uPA) in breast cancer. METHODS: Applying streptavidin biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in 100 patients with primary breast cancer. RESULTS: There were 55 patients with high uPA expression, and 45 with low expression. There was significant correlation between uPA expression and TNM stage, lymph node status, tumor size. Neither age, menopausal status, nor ER status was significantly related with level of uPA expression Patients with high expression of uPA had significantly shorter disease-free survival period and overall survival than did those with low expression of uPA. Univariate analysis showed that uPA as a prognostic factor was of similar magnitude to lymph node status and TNM stage, but stronger than that of ER status and tumor size. uPA was an independent prognostic factor affecting disease-free survival and overall survival. CONCLUSION: uPA appears to be a strong and independent biologic marker for predicting prognosis of breast cancer. PMID- 11776835 TI - [Study of microsatellite instability of colotectal cancer and its clinical significance]. AB - OBJECTIVE: To evaluate microsatellite instability (MI) of colorectal cancer in China. METHOD: Replication error (RER) status was examined by using 6 microsatellite loci D2S123, D2S119, D13S160, D8S282, D3S1293 and D18S58. The loci were amplified by PCR technique. The PCR products were separated on denatured polyacrylamide gel and then silver stained. RESULTS: Of the 60 cases of colorectal cancer studied, 20 (33.3%) showed MI, 11 cases (18.3%) were RER positive. In 11 RER-positive cases, 4(36.4%) had family history of malignant tumor, while only 8.2% had positive family history in RER-negative cases (P < 0.05). The RER-positive patients were younger, and their cancer occurred more frequently in the colon with invasive type of growth. There were more cancers in Dukes III and IV in the REF-positive patients. In 5 colorectal cancer cases associated with adenoma, MI was detectable in 4 adenomas. CONCLUSION: MI phenotype might be present ubiquitously in sporadic colorectal cancers in China. Its frequency is comparable to that of other reports. MI is a relatively early molecular event in the genesis of colorectal cancers. RER is a useful sign of susceptibility to the development of colorectal cancer. PMID- 11776836 TI - [Immunohistochemistry and DNA content of gastro-intestinal carcinoid]. AB - OBJECTIVE: To study the relationship between clinical pathology and antigen expression and DNA content of gastrointestinal carcinoid tumors. METHODS: Fifty two cases of paraffin-embedded gastrointestinal carcinoid specimens were collected. According to Gould's criteria, there were 20 cases of typical carcinoid, 20 cases of atypical carcinoid and 12 cases of undifferentiated carcinoid. Ten different kinds of antigen were examined by immunohistochemical staining and DNA contents by flow cytometry. RESULTS: Calcitonin (CT), carcinoembryonic antigen (CEA) and vasoactive intestinal peptide (VIP) expression was significantly reduced in typical carcionoid compared to that in other two types of carcionoid. Their expression was more marked in progression than in early stage of the disease. VIP expression was significantly higher in patients with than without lymph node metastases. Cellular DNA analysis showed significant difference between the typical and the other two types of carcinoid. Tumors with expression of VIP and CEA were mostly aneuploid. CONCLUSION: To study expression of relevant antigens in gastrointestinal carcinoid in relation to histological type and cellular DNA content helps determine its biologic behavior and prognosis. PMID- 11776837 TI - [Expression and characteristics of laryngeal carcinoma-associated antigen]. AB - OBJECTIVE: To study the characteristics of laryngeal carcinoma-associated antigen (LCAA) and its expression on laryngeal carcinoma tissue. METHODS: The binding of a cocktail monoclonal antibodies Lc9, Lc11, Lc12 to human laryngeal squamous-cell carcinoma, laryngeal precancerous lesions and normal laryngeal mucosa was examined by immunohistochemical method. LCAA isolated and purified by gel filtration, and chromotography from 3 laryngeal squamous-cell carcinomas. The reactivity of the purified antigen was determined after treatment with trypsin, NaIO4, methanol and heating. RESULTS: The positive rate of LCAA expression in 90 cases of laryngeal carcinoma, 14 cases of precancerous lesions and in 10 cases of normal laryngeal mucosa was 97.7%, 50.0% and 0, respectively. LCAA was a glycoprotein, moderately heat stable. The purified antigen gave two bands of apparent molecular weights of 61,400 and 56,500 on SDS-PAGE and Western blot. CONCLUSION: The results provide a basis for immunoimaging diagnosis and targeting chemotherapy for laryngeal cancer. PMID- 11776838 TI - [Comparative study of conventional CT and spiral CT in diagnosis of lung cancer]. AB - OBJECTIVE: To observe and compare the findings of lung cancer with conventional CT and spiral CT. METHODS: One hundred and thirty-four cases of pathologicalty confirmed lung cancer, including 56 centrally located and 78 peripherally located lung cancer, were examined by conventional CT and spiral CT, and their findings compared. RESULTS: In 30 of the 56 cases with central lung cancer, the lesion was located in the right bronchus and in 26 of them the lesion was in the left bronchus. On spiral CT, the display rate of obstructive findings and invasion to big vessels in the mediastinum was higher than that on conventional CT. There was no remarkable difference in density of the lesion and detection of metastasis in hilar and mediastinal lymph nodes between conventional and spiral CT. In 34 of the 78 cases with peripheral lung cancer, the lesion was in the right lung and in 44 was the lesion in the left lung. Calcification, air-bronchogram, cavity and pleural indentation of the lesion in the peripheral lung cancer were better displayed by spiral than by conventional CT. CONCLUSION: Spiral CT is superior to conventional CT in the observation of signs characteristic of central and peripheral lung cancers. PMID- 11776839 TI - [Efficacy of transcatheter arterial infusion chemotherapy and transcatheter arterial embolization in 132 patients with primary hepatocellular carcinoma]. AB - OBJECTIVE: To find out factors influencing efficacy of transcatheter arterial infusion chemotherapy (TAI) and transcatheter arterial embolization (TAE) for unresectable primary hepatocellular carcinoma. METHODS: From January 1993 to October 1997, 132 patients with unresectable primary hepatocellular carcinoma (HCC) received 597 intervention treatments. Of the 132 patients, 122 patients were given TAI plus TAE (92.4%), while the remaining 10 patients were given TAI alone (7.6%). RESULTS: The 1-, 2-, and 3-year overall survival rate was 81.8%, 36.4% and 18.2%, respectively. The clinical stage of the disease, the embolizing agents used and their dosage, formation of collateral circulation to the tumor and proper application of superselective hepatic arterial catheterization are factors affecting treatment efficacy. CONCLUSION: Adequately performed TAI and TAE can be routinely used for the treatment of unresectable liver cancer. PMID- 11776840 TI - [The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma]. AB - OBJECTIVE: To analyse the effect of preoperative transcatheter hepatic arterial chemoembolization(TACE) on disease-free survival rate after surgical excision for hepatocellular carcinoma(HCC), in order to evaluate its therapeutic significance. METHODS: The history of 1,457 cases of HCC with long term follow-up who received curative or relatively curative tumor resection was reviewed. Among these patients, 120 received preoperative TACE. Factors of prognostic significance were analysed using Cox proportional hazards survival mode, and the disease-free survival was analysed by Kaplan-Meier estimation. RESULTS: Multivariate analysis revealed that the factors of prognostic significance were number and size of tumor mass and its gross type, number and efficacy of TACE treatment, presence of tumor thrombus, satellite nodules, vascular invasion, and postoperative AFP level. The 5-year disease-free survival rate following surgery of patients who received TACE twice or more was 51.0%, while that of patients who received TACE once and none was 35.5% and 21.4%, respectively. The mean disease-free suvival time in these 3 groups of patients was 66.4, 22.5 and 12.5 months, respectively. For patients whose TACE treatment was effective, the 5-year disease-free survival rate was 56.8%, with a mean disease-free suvival time of 90.1 months. CONCLUSION: Preoperative TACE is so far the most feasible approach to improve disease-free survival of HCC patients. PMID- 11776841 TI - [The use of intervention chemotherapy in comprehensive treatment of advanced nasopharyngeal carcinoma]. AB - OBJECTIVE: To study the application of intervention chemotherapy in the comprehensive treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: In 30 patients with advanced NPC, combined intervention chemotherapy with cisplatin (100 mg), 5-fluoro-uracil (1,000 mg) and bleomycin (16 mg) was given by Seldinger's selective unilateral catheterization of the ascending pharyngeal artery or superior maxillary artery. If the lesion had extended over the midline, the intervention chemotherapy encompassed both sides: 2/3 of the dose infused to the side with the major lesion and 1/3 to the other side. Radiotherapy started one week after intervention chemotherapy. A total dose of 60-70 Gy was given to the primary tumor or 50-60 Gy to the cervical metastases in 8 weeks. Fifty patients with advanced NPC treated in the same period of time with radiotherapy alone served as the control. Both groups of patients were treated with 60Co, the duration of treatment and dose splitting were the same. RESULTS: After intervention chemotherapy, the primary tumor mass reduced in size in 16 patients and the enlarged cervical lymph nodes shrank or became loosened in 12 patients. The radiation dose required to achieve complete response of the primary and metastatic lesions was significantly less as compared to that of patients receiving radiotherapy alone (P < 0.05). At four weeks following completion of radiotherapy, complete response rate in the two groups of patients was 83.3% and 72.0%, respectively (P < 0.05). CONCLUSION: Intervention chemotherapy combined with radiotherapy is an effective treatment for patients with advanced NPC. PMID- 11776842 TI - [Mitomycin, vindesine and cisplatin combination therapy in the treatment of advanced non-small cell lung cancer: a report of 108 cases]. AB - OBJECTIVE: To evaluate the results of combination chemotherapy with mitomycin (MMC), vindesine (VDS) and cisplatin (DDP) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 108 patients with advanced NSCLC was enrolled in this study. Adenocarcinoma (74 cases) and squamous-cell carcinoma (23 cases) were the most common type of malignancy. Thirty patients received prior chemotherapy while 78 did not. RESULTS: Complete response was observed in 1 patient and partial response in 36 patients with an overall response rate (RR) of 34.3%. The RR was significantly higher in the previously untreated patients (41.0%) and than that in the pretreated patients (P = 0.0169). The RR did not significantly differ between patients with squamous--cell carcinoma (30.4%) and adenocarcinoma (32.4%). That of patients with metastases to the lymph nodes, to the other parts of lung, liver and bone was 43.1%, 32.4%, 25.0% and 0, respectively. The median response duration was 3 months and the median survival period was 7 months. The dose limiting toxicity was neutropenia, which was in grade III and IV in 41.7% of the treated patients. Grade III and IV thrombocytopenia was observed in 6.5% and grade III and IV nausea and vomiting in 21.3% of the treated patients. CONCLUSION: A higher response rate is attainable in patients with advanced NSCLC treated by MMC, VDS and DDP with tolerable toxicity. PMID- 11776843 TI - [Gastric cancer in the young]. AB - OBJECTIVE: To determine the clinico-pathological characteristics of young patients with gastric cnacer. METHODS: From January 1968 through January 1993, among 6098 gastric cancer patients admitted for surgical treatment, 312 (5.1%) were < 35 years of age. The clinico-pathological data of these young patients were reviewed and compared to those of patients in the other age groups. RESULTS: In this series of young patients, female predominated. Histologically, there were more cases with poorly differentiated (49.2%) and muco-cellular (26.6%) adenocarcinoma. The most common gross morphology observed was of Borrmann type III (38.1%) and type IV (36.9%). The mojority of patients (83.3%) were in TNM stage III and stage IV. CONCLUSION: The prognosis of young patients with gastric cancer surgically treated is poor. This is due to the fact that most of them are in late stage and their cancers are poor in differentiation rather than their young age. To increase the awareness of cancer in apparently healthy young persons is important for early diagnosis and treatment, and better prognosis. PMID- 11776844 TI - [Primary esophageal small-cell carcinoma]. AB - OBJECTIVE: To study the clinical biocharacteristics of primary esophageal small cell carcinoma (PESC) and factors influencing prognosis and to find rational surgical indications and combined therapy. METHODS: To analyse the clinical materials of 47 patients undergone operation with PESC compared with those of patients with esophageal squamous-cell carcinoma(ESCC) or primary esophageal adenocarcinoma (PEAC). RESULTS: The overal resectability, morbidity and 30-day mortality rate of PESC was 93.6%, 17% and 2.1%, respectively, being similar to those of ESCC or PEAC. TNM staging, lymph node metastasis were the major determinants influencing long-term survival. Tumor length, depth of tumor invasion and type of operation had little influence on long-term prognosis. The 5 year survival rate of PESC was 7.5%, which was much lower than that of ESCC and PEAC (P < 0.01). Among the 42 deceased patents, one died of anastomotic leakage and the others died of remote metastasis and recurrence. Adjuvant chemotherapy did no help improve patients long-term survival. CONCLUSION: Campared with ESCC and PEAC, PESC is the most malignent one with early lymphatic and hematogenous matastases and poor prognosis. Lymph node metastasis is the major factor influencing prognosis. Patients in stage 0, I and II a of PESC are indicated for surgical resection, while those in stage II b, III and IV should be managed with non-surgical combined therapy. PMID- 11776845 TI - [Treatment and outcome of cervical lymph nodal metastases of unknown primary sites]. AB - OBJECTIVE: To ascertain the optimal management of cervical nodal metasta of unknown primary sites. METHODS: The clinical data of 114 patients of cervical nodal metastases of unknown primary sites were retrospectively analyzed. RESULTS: For metatic masses of the upper and/or middle part of the neck, the optimal approach varied depnding on the histologic type. Poorly-differentiated carcinoma was treated with radiotherapy, squamous-cell carcinoma was treated with radiotherapy plus surgery, while papillary adenocarcinoma was treated by combined radical thyroidectomy. Their 5-year survival rate was 45.2%, 53.8% and 62.5%, respectively. For metastatic masses in the supraclavicular region, chemotherapy was the first treatment of choice in all patients. In only 12 of the 114 patients (11.2%) the primary sites were found in the follow-up period. CONCLUSION: For patients with cervical lymph node metastases from unknown primary sites, the management should be given according to the location of lymph node involved and histopathologic type of the tumor. PMID- 11776846 TI - [Effect of exogenous p16 gene on the growth of wild-type p53 human lung adenocarcinoma cells]. AB - OBJECTIVE: To study the effect of p16 gene on human adenocarcinoma cell lines and the posibility of exogenous p16 gene for gene therapy of lung cancer. METHODS: A p16 gene recombinant expression vector was constructed by cloning p16 cDNA into the pcDNA3 vector at the sites of BamH1 and Xho I, and was transferred by electroporation into p16 gene deficient human lung adenocarcinoma cell lines (A549 and H460) which expressed wild-type p53 gene. The p16 mRNA and protein expression of A549-p16 and H460-p16 cell was detected by Northern blots and immunocytochemistry, respectively. The cell growth properties and cell cycle pattern were aassessed by flow cytometry. RESULTS: The growth and colony forming efficiency of A549-p16 and H460-p16 cells were significantly inhibited compared with the controls. Flow cytometry showed A549-p16 and H460-p16 cells were arrested in G1 phase of cell cycle, and the percentage of cells in S phase and G2/M phase was decreased significantly. Tumorigenicity of the A549-p16 and H460 p16 cells in nude mice was greatly inhibited. CONCLUSION: The results show that human p16 gene can suppress the malignant phenotype of wild-type p53 human lung adenocarcinoma cell lines (A549 and H460). p16 gene can play a role in the gene therapy of human lung adenocarcinoma. PMID- 11776847 TI - [Mutation of human mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) families]. AB - OBJECTIVE: To investigate germline mutations of mismatch repair genes hMLH1 and hMSH2 in 29 HNPCC families. METHODS: Mutations were detected by PCR-SSCP analysis, and confirmed by DNA sequencing. RESULTS: (1) In 29 families, the overall mutation rate of these two genes was 31.0% (9/29). Mutation detected in all of the 9 families was located in the hMLH1 gene, indicating that the hMLH1 gene was the main responsible gene in these families. An obvious difference was observed when compared to the mutation rate in the control group (P < 0.01); (2) All of the 10 family members who developed colorectal cancer (CRC) harbored the same mutation as detected in their proband, indicating a strong association between gene mutation and development of CRC. In 29 healthy family members, 5 asymptomatic carriers of mutation were found who were considered as the high-risk populations of CRC. CONCLUSION: A certain number of HNPCC families can be benefited from the genetic screening for mutation of the mismatch repair genes. PMID- 11776848 TI - [Alterations of FHIT gene and p16 gene in lung cancer and metastatic hilar lymph nodes]. AB - OBJECTIVE: To investigate alterations of fragile histidine triad (FHIT) gene and p16 gene in lung cancer. METHODS: Forty-nine lung cancer specimens and 16 matched metastatic hilar lymph nodes of lung cancer patients were examined for abnormalities of p16 and FHIT genes by using RT-PCR and RT-PCR-SSCP. RESULTS: Thirty-two of 47(68.1%) samples of primary lung cancer and 15 of 16 (93.8%) samples of metastatic hilar lymph nodes exhibited loss of FHIT gene transcripts. In 14 of the 47 samples of primary lung cancer(29.8%), and 9 of 16 samples of metastatic hilar lymph nodes(56.3%), FHIT gene transcripts were deleted in exones 1-4. The deletion rate of p16 gene transcripts in exons 2-3 was 36.7% (18/49) in primary and 56.3% (9/16) in metastatic lymph nodes, respectively. The loss of p16 or FHIT expression did not correlate with sex, smoking, TNM stage, but was more frequently observed in poorly differentiated cancer. No mutation of FHIT and p16 cDNA was found by SSCP. CONCLUSIONS: Loss of FHIT and p16 gene transcript is frequent in lung cancer and may be an early event in lung carcinogenesis. Mutations may not be the major mechanisms of p16 and FHIT gene inactivation. Lung cancer with FHIT and p16 gene alterations have more malignant phenotype and behavior. PMID- 11776849 TI - [Clinical significance of multidrug resistance-associated protein(MRP) gene expression in non-small cell lung cancer]. AB - OBJECTIVE: To investigate expression of multidrug resistance-associated protein (MRP) in non-small cell lung cancer and its relation to histological type, TNM staging and prognosis. METHODS: In situ hybridization was used to examine mRNA expression of MRP. RESULTS: The overall positive rate of MRP expression was 74.1%, with 73.3% and 72.0% in adenocarcinoma and squamous-cell carcinoma, respectively. The expression of MRP was not related to histological subtypes, TNM staging and cell differentiation. In 47 patients who received chemotherapy, 35 patients with positive MRP expression(+(-)++) showed worse prognosis than in those with negative expression (P < 0.05). The median survival time was 8.7 months and 21 months in patients with positive and negative MRP expession, respectively. In patients with squamous-cell carcinoma, the survival rate was significantly lower in patients (n = 12) with positive MRP expression than in those (n = 7) with negative MRP expression (P < 0.05). Their median survival time was 6 months and 19.5 months, respectively (P < 0.05). CONCLUSION: The expression of MRP gene is negatively correlated with survival of patients with squamous-cell carcinoma, but not adenocarcinoma, who received chemotherapy. PMID- 11776850 TI - [p53 mutations and protein overexpression in primary colorectal cancer and its liver metastasis]. AB - OBJECTIVE: To compare p53 status between primary and hepatic metastatic colorectal cancer in 34 patients. METHODS: p53 gene status (exon 5-9) was examined by PCR, denaturing gradient gel electrophoresis (DGGE) and automated sequencing. p53 protein was detected by immunohistochemistry using monoclonal antibody DO-7. RESULTS: p53 mutations were found in exons 5 through 9 in 21 of 34 patients (61.8%). Among them, 5 patients had mutation in liver metastasis but not in their primary tumor while in the other 4 patients the same mutations were found in both primary and metastatic colorectal cancers. In no patients was p53 mutation exclusively found in the primary colorectal tumor. Moreover, additional mutation was detected in the metastatic lesions in two cases. Of the 37 mutations within the exons examined, 73% was missense mutation and 16% was nonsense mutation. There were 4 microinsertions. p53 protein was overexpressed in both primary and metastatic colorectal cancers with p53 gene mutations. The presence of p53 mutations significantly correlated with p53 protein accumulation (r = 0.96, P < 0.001). However, in 4 patients with p53 nonsense mutation, immunohistochemical staining was negative. In three patients who showed no p53 mutation of the primary tumor, p53 protein was consistently over-expressed. CONCLUSION: In colorectal cancer, p53 gene mutation usually appears first in the primary tumor and maintains as such but more prominent when metastasized to the liver. However, p53 gene mutation may occur only after being metastasized. Although p53 gene mutation and p53 protein overexpression correlate with each other, either parameter examined alone may lead to false positive results. PMID- 11776851 TI - [Expression of P-glycoprotein in benign and malignant gallbladder neoplasms]. AB - OBJECTIVE: To evaluate the relationship between P-glycoprotein expression and anti-cancer drug resistance of gallbladder carcinoma and the use of P glycoprotein as a biomarker of gallbladder carcinoma, the expression of P glycoprotein was detected in benign and malignant gallbladder neoplasms and normal gallbladder tissues. METHODS: Alkaline phosphatase anti-alkaline phosphatase (APAAP) method was used to detect the expression of P-glycoprotein in different gallbladder tissues (gallbladder carcinoma, 26 cases; benign gallbladder neoplasm, 14 cases; and normal gallbladder tissue, 9 cases). The relationship between expression of P-glycoprotein, TNM stages and other clinical data of gallbladder carcinoma was also analyzed. RESULTS: Immunohistochemical staining with a monoclonal antibody JSB-1, P-glycoprotein was positive in 76.9% (20/26) of gallbladder carcinomas, in 35.7% (5/14) of benign gallbladder neoplasms and in 33.3% (3/9) of normal gallbladder tissues (P < 0.05). With another monoclonal antibody UIC-2, the positive rates were 69.2% (18/26), 21.4% (3/14) and 11.1% (1/9), respectively (P < 0.01). There was no significant correlation between P-glycoprotein expression and gallbladder carcinoma TNM staging. CONCLUSION: The results suggest that P-glycoprotein probably plays an important role in the poor response of gallbladdar carcinoma to chemotherapeutic agents. In addition, P-glycoprotein may be used a valuable biomarker of gallbladder carcinoma. PMID- 11776852 TI - [Characteristics of high frequency 249 codon mutation of p53 gene in hepatocellular carcinoma in prevalent area of China]. AB - OBJECTIVE: To study the characteristic features of an unique hotspot missense mutation of the 249 codon of p53 gene demonstrated in human hepato-cellular carcinoma(HCC) in a region of high(Qidong) and low (Beijing) exposure to both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in China. METHODS: Surgical samples from 97 HCC from Qidong and 22 from Beijing, China, collected in 1994 through 1997, were studied. The 249 codon mutation of p53 gene was detected by PCR followed by HaeIII RFLP analysis and DNA sequencing. Intracellular p53 protein level was determined by immunohistochemical staining. RESULTS: High mutation rate of 249 codon of p53 gene was consistently found in recent years, with an average of 53.6% (52/97). No such mutation was identified in 22 Beijing HCC collected in the same time period. The genotype of p53 249 codon mutants which showed heterozygous profile was identified to be homozygous in nature following tumor tissue enrichment. Of 21 HCC shown to have 249 codon mutation, 20 exhibited high intranuclear accumulation of p53 protein. p53 protein staining was negative in the surrounding noncancerous hepatic tissue. CONCLUSION: The high frequency of homozygous mutation of the 249 codon of p53 gene accompanied with p53 protein accumulation provides important enlightenment in the understanding of hepatocarcinogenesis and clinical application of gene therapy and/or immunotherapy for HCC. PMID- 11776853 TI - [Helicobacter pylori infection and expression of PCNA, p53, c-erbB-2 in carcinoma and precancerours lesions of the stomach]. AB - OBJECTIVE: To study the role of Helicobacter pylori (Hp) in gastric carcinoma. METHODS: Hp was examined in 70 patients with gastric carcinoma, 62 patients with pre-malignant lesions and 16 controls by improved Warthin-Starry method and PCNA, p53, cerbB-2 protein examined immunohistochemically. RESULTS: The frequency of Hp infection in gastric carcinoma and its precusor lesions was significantly higher than that in the controls. There was no significant difference in Hp infection rate between gastric carcinoma and its precursor lesions, nor between the intestinal type and diffuse type of gastric carcinoma. Hp infection correlated well with expressions of PCNA, c-erbB-2 and with co-expression of PCNA, p53 and c erbB-2 in gastric carcinoma and its precusors. p53 protein was expressed only in gastric carcinoma, and its expression level was higher in the presence than in the absence of Hp infection (P < 0.01). CONCLUSION: Hp might act as a tumor promoter in the genesis of gastric cancer. PMID- 11776854 TI - [Imaging findings of fibrolamellar hepatocellular carcinoma]. AB - OBJECTIVE: To describe the imaging findings of fibrolamellar hepatocellular carcinoma(FL-HCC). METHODS: Imaging studies in 11 patients with pathologically confimed F1-HCC were reviewed. There was no cirrhosis or hepatitis according to patients' history. Serum alpha-fetoprotein level was normal in all patients. Imaging studies included ultrasonography(US) in 10 patients, CT in 11, MRI in 8, and angiography in 9. RESULTS: (1) On US, the echogenicity of the tumor was hyperechoic relative to normal liver in four patients, and mixed in six. Cyst like regions with various sizes were found within the masses in four patients, Doppler US revealed that the solid portion of the tumor was hypervascullar. (2) Nonenhanced CT scan demonstrated a well demarcated, solitary mass in 9 patients, and a multilobulated mass in 2. All masses were non-homogeneous and hypodense to the liver. Seven of the lesions had a central lower density region with radiating pattern which was confirmed as densely packed scar by pathologic examination. Punctate calcification was seen in 4 of 11 patients. Marked contrast enhancement of the masses was seen on the arterial dominated phase in 7 patients under enhanced CT, and a central nonenhanceing scar-like structure was found in 4 of the seven patients, Liver cirrhosis and splenomegaly were not found in this series. (3) On MRI, the tumor was hypointense relative to the liver parenchyma on T1-weighted spin-echo image and non-homogeneous hyperintense on T2-weighted image. Six of the eight patients had a central radiate-like structures which were hypointense on both T1 and T2-weighted images. On contrast enhanced MRI, four of five patients had obvious enhancement, and the central scar did not enhance on both early and delayed enhancement. (4) On angiography, a globular hypervascular mass with neovascularity was found in four of the nine patients. Peripheral nodular tumor stain, which was similar to that of hemangioma, was seen in 3 patients. A hypovascular mass with displacement of the adjacent vessels was found in 2 cases. No tumor thrombus in the portal vein, nor arterial shunting to the portal vein was identified. CONCLUSION: Typical imaging features in young patients of a large hepatic mass with central scar and calcification but without cirrhosis might be suggestive of FL-HCC. PMID- 11776855 TI - [Dynamic enhanced spiral CT characteristics of recurrent nasopharyngeal carcinoma and radiofibrosis]. AB - OBJECTIVE: To study the characteristics of dynamic enhanced density-time curves of recurrent nasopharyngeal carcinoma(RNPC) and radiofibrosis(RF) in spiral CT. METHODS: Fifty cases of RF and 46 cases of RNPC were examined both before and after contrasting in spiral CT. The CT values of the regions of interest (ROI) at various acquisition time (0, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, and 300 sec after the beginning of the contrast injection) were collected. The difference in CT value of various acquisition time was analysed statisticaly and the dynamic enhanced density-time curves were established. RESULTS: The typical curve in RF group was a slowly ascending-slowly descending one. Its peak CT value as seen at 210 sec postcontrast and measured 60.1 +/- 2.57 Hu. That of the RNPC was of rapidly ascending-slowly ascending-slowly descending one. Its peak CT valne was seen at 150 sec postcontrst and measured 75.4 +/- 7.2 Hu. The differences of CT values were significant between RNPC and RF from 40 to 300 sec postcontrast (P < 0.001). CONCLUSION: The different characteristics of the dynamic enhanced desity-time curves and CT values of the ROI may provide important informations for differential diagnosis of RNPC and RF. PMID- 11776856 TI - [Evaluation of CT in the diagnosis of esthesioneuroblastoma]. AB - OBJECTIVE: To assess the role of CT in the diagnosis, staging and post-treatment follow-up of esthesioneuroblastoma. METHODS: Thirteen cases of pathologically comfirmed esthesioneuroblastoma were analysed retrospectively. RESULTS: On preoperative check up, according to Kadish staging, no case was in stage A, 4 cases were in stage B, 7 in stage C. Tumor scans showed soft tissue density. In 3 cases, calcification was found inside of the tumor. In the 4 cases on scan and enhanced CT, the tumors were heterogeneously enhanced in 3. On enhanced CT, the tumor density was obviously higher than that of the surrounding soft tissue in 6 cases. Postoperative follow-up CT revealed tumor recurrence within 3 months to 2 years in 4 cases. Tumor invasion involved nasal cavity and ethmoid sinus(13 cases), maxillary sinus (12 cases), sphenoid sinus(10 cases), frontal sinus (2 cases), orbit (7 cases). Intracranial invasion occurred in 3 cases, and lymph node metastases in 4 cases. CONCLUSION: CT is valuable in pre-operative staging and monitoring recurrence of esthesioneuroblastoma. Although esthesioneuroblastoma has characteristic CT features on enhancement and multiple invasions to neighboring structures, reliable diagnosis is dependent on pathological confirmation. PMID- 11776857 TI - [Clinico-pathologic characteristics of malignant thymoma]. AB - OBJECTIVE: To assess the histopathology, clinical staging and treatment of malignant thymoma in relation to prognosis. METHODS: Sixty four cases with malignant epithelial thymic tumors treated in the period of 1958-1995 were retrospectively studied. Archived specimens were categorized according to Levine and Rosai into type I malignant thymoma(MT) and type II thymic carcinoma (TC). MT was histologically classified according to Muller-Hermelink(M-H). Clinical staging was ascertained according to Masaoka's criteria. RESULTS: There were 41 cases of MT and 23 cases of TC. No medullary or mixed thymoma was observed in this series of MT. The 5-year survival rate of patients with MT of predominantly cortical, cortical, and well-differentiated thymic carcinoma (MDTC) subtypes was 75.3%, 44.7% and 43.3%, respectively. That of patients with TC of squamous-cell carcinoma and lympho-epithelioid subtypes was 27.5% and 60.0%, respectively. The 10-year survival rate of these 5 subtypes was 25.3%, 10.0%, 0, 0, 20.0%, respectively(P < 0.05). The 5-year and 10-year survival rates decreased with increase in staging. In 22 patients in stage III and IV who received thoracotomy with biopsy only, their survival rate was significantly lower than that in patients with their tumor resected. CONCLUSION: Histomorphology of the tumor, heterogeneity in cell types, clinical staging and the extent of tumor resection are factors affecting survival. PMID- 11776858 TI - [The role of hysterectomy in the therapy of gestational trophoblastic tumor]. AB - OBJECTIVE: To evaluate the role of hysterectomy for patients with gestational trophoblastic tumor. METHODS: A total of 68 cases of gestational trophoblastic neoplasia treated by hysterectomy from 1985-1997 at PUMC hospital was retrospectively analyzed. Thirty-eight cases were diagnosed as choriocarcinoma and 30 as invasive mole. RESULTS: Twenty-three elder patients who didn't desire to preserve fertility were selected for hysterectomy after short courses of chemotherapy. Twenty-two of them had complete remission (95.6%). The average total course of chemotherapy was 4.2. Of twenty-seven chemo-refractory cases who were suspected of an isolated lesion in the uterus, delayed hysterectomy as an adjunct to chemotherapy was performed. Twenty of them achieved complete remission (74.1%), with an average 9.4 courses of chemotherapy. Emergency hysterectomy was indicated in 18 patients with uterine perforation or life-threatening hemorrhage. Seventeen of the emergent cases had complete remission (94.4%), who had received an average 7.6 courses of chemotherapy. CONCLUSION: Although the development of effective chemotherapy has resulted in improved survival of patients with gestational trophoblastic tumor, hysterectomy remains an important adjunct treatment in a selected subset of patients. Modified radical hysterectomy is recommended for the indicated patients. PMID- 11776859 TI - [Surgical treatment of ovarian malignant tumors metastasized to the gastro intestinal tract: a report of 131 cases]. AB - OBJECTIVE: To investigate the value and feasibility of surgical excision of gastro-intestinal metastatic tumors in patients with ovarian malignancy. METHODS: The surgical and clinical data were retrospectively reviewed in 131 cases of ovarian malignant tumor with surgically excised gastrointestinal metastasis (> or = 2 cm in diameter). RESULTS: Ovarian malignant tumor with gastro-intestinal metastasis accounted for 28.9% of the patients with primary ovarian malignancies in the same time period. Of the 131 cases, 126(93.9%) were in stage III and IV. The treatment was surgical excision combined with chemotherapy. Of the 141 operations, 83 (58.9%) were done by stripping of tumors on the gastro-intestinal wall and repair, 31(22.0%) received resection of the involved segment of the bowel with anastomosis, 27(19.2%) with colostomies. Postoperative complications occurred in 26.9% of the operated patients. The overall 2- and 5-year survival rate was 79.7% and 42.5%, respectively. CONCLUSION: Surgical excision of gastro intestinal tumors metastasized from primary ovarion malignancies is feasible to achieve cytoreduction. Prognosis can be improved when combined with chemotherapy. PMID- 11776860 TI - [Analysis of patients survived over ten years after resection of gastric cardia carcinoma]. AB - OBJECTIVE: To investigate factors affecting long-term survival in patients with resected gastric cardia cancer. METHODS: Survival was analyzed retrospectively in 584 patients with gastric cardia carcinoma who received tumor resection from 1964 through 1982. RESULTS: The 10-year survival rate was 17.1%. The major factors influencing survival were clinical staging, degree of differentiation, gross tumor type and size (P < 0.05) and status of lymph node metatasis (P < 0.01). Residual tumor at resection edge and tumor thrombi did not significantly affect survival, nor did sex/age, and course of the disease. CONCLUSION: Early detection, early diagnosis and early surgical resection are the key to improve 10 year survival of patients with resected cancer of the gastric cardia. Why residual tumor left at the resection edge and the presence of tumor thrombi do not influence survival needs to be further studied. PMID- 11776861 TI - [Transurethral microwave tissue coagulation therapy for carcinoma of urinary bladder: an analysis of 35 patients]. AB - OBJECTIVE: To study the reliability of transurethral microwave tissue coagulation therapy for transitional epithelial carcinoma of the urinary bladder. METHODS: The suitable microwave output was affirmed by studying its coagulation effect on pig and human bladder wall according to histo-morphologic changes: Based on this study, transurethral microwave tissue coagulation of bladder cancer (TUMTCBC) was carried out in 35 patients with bladder carcinoma. Biopies were taken from the microwave irradiated sites after the procedure. All patients were given regular intravesical chemotherapy with mitomycin C after microwave treatment and were followed-up for a mean of 56 months. RESULTS: The treatment was effective in all of the treated patints. The recurrence rate and the tumor-free period in patients treated with TUMTCBC was comparable to those in patients treated with transurethral electric cauterization or partial cystectomy. In 19 cases (54.3%), no recurrence of tumor was found in 5 years. CONCLUSION: TUMTCBC is safe, effective and easy to perform. It may be used for the treatment of both superficial and invasive bladder carcinoma. PMID- 11776862 TI - [Comparative study of three different chemotherapy protocols for advanced non small-cell lung cancer]. AB - OBJECTIVE: To compare the efficacy and toxicity of three different chemotherapy protocols for advanced non-small-cell lung cancer (NSCLC). METHODS: The clinical data of 93 cases with advanced NSCLC treated with (1) ifosfamide plus vindesine plus cisplatin (IVP, 31 cases), (2) mitomycin C plus vindesine plus cisplatin (MVP, 30 cases), and (3) cyclophosphamide plus adriamycin plus cisplatin (CAP, 32 cases) were analysed. RESULTS: The response rate was 48.4% in patients treated with IVP, 40.0% in those treated with MVP, and 28.1% in those with CAP, respectively. The major toxic reactions in the three groups were tolerable myelo suppression and hair loss. CONCLUSION: IVP and MVP are effective and safe chemotherapeutic protocols for the treatment of advanced NSCLC patients. PMID- 11776863 TI - [Clinical analysis of 935 cases of non-Hodgkin's lymphoma]. AB - OBJECTIVE: To analyze the results of treatment of non-Hodgkin's lymphoma (NHL). METHODS: The results of treatment in 935 NHL patients were reviewed according to life table Log rank analysis. RESULTS: Patients with moderately malignant NHL had better long-term survival, as compared with other pathologic types (P < 0.05). Patients in clinical stage I had better prognosis than those in stage II, III and IV (P < 0.001). Patients achieved CR as short-term response had the best prognosis. When analyzed according to treatment modalities, the long-term effect was seemingly better in patients treated with chemotherapy + radiotherapy than in patients treated with radiotherapy alone or chemotherapy alone, but the different was statistically insignificant. If the results are compared between patients treated in 1983 through 1988 and those in 1989 through 1993, there was marked improvement in long-term survival in the latter time period during which patients were given more intensive chemotherapy. CONCLUSION: The long-term survival rate of patients with NHL was closely related to pathologic types, clinical stage, short-term therapeutic effect. Intensive chemotherapy help improve prognosis. The leaping manner of NHL dissemination requires sufficient systematic therapy. PMID- 11776864 TI - [Cloning of differentiation-related genes induced by all-trans retinoic acid(ATRA) from human lung cancer GLC-82 cell line]. AB - OBJECTIVE: Cloning of differentiation-related genes induced by all-trans retinoic acid(ATRA) from human lung cancer GLC-82 cell line. METHODS: The difference in gene expression between human lung cancer cell GLC-82 before and 8, 24 hours and 4 days after ATRA treatment was investigated by an improved protocol of mRNA differential display with SYBR Green I, a highly sensitive fluorescent stain. RESULTS: There were obvious differences in gene expression between human lung cancer cells before and after ATRA treatment. The expression of some genes was decreased or inhibited while that of other genes was activated temporarily or persistently. Three cDNA fragments of the differentially expressed genes were cloned and analyzed. CONCLUSION: ATRA plays an important role in regulating the differentiation-related gene expression. ATRA-induced differentiation is a complex process with multiple genes involved. PMID- 11776865 TI - [Apoptosis of human melanoma cell line WM-983A by p16 gene transduction]. AB - OBJECTIVE: To further understand the mechanism of action of the tumor-suppressor gene p16. METHODS: An adenoviral expression vector with full length cDNA of p16 gene insert was constructed (Ad-p16) and transfected into WM-983A cells, the p16 gene of which was point mutated at codon 126. The effect of exogenous p16 gene on the growth of WM-983A cells was examined in vitro and in vivo. RESULTS: Expression of p16 gene in WM-983A cells was confirmed by Western blot. The in vitro growth of the Ad-p16 transfected WM-983A cells was significantly inhibited (inhibition rate: 78%) as compared to mock (Ad-LacZ) transfected WM-983A cells. Colony-forming activity in vitro of the Ad-p16 transfected WM-983A cells was completely inhibited. Morphologically, the Ad-p16 transfected cells appeared apoptotic which was confirmed by the appearance of pre-G1 on flow cytometry and DNA fragmentation. The growth of WM-983A xenografts in nude mice was retarded by intra-tumoral injection of Ad-p16. CONCLUSION: p16 gene participates in the induction of cell apoptosis. It is promising to use it for gene therapy of cancer, especially when combined with other apopptosis-inducing agents. PMID- 11776866 TI - [Preparation of monoclonal antibodies to human vascular endothelial growth factor(VEGF121) and identification of its expression on gastric carcinoma cell line MGC803]. AB - OBJECTIVE: To further elucidate the source of VEGF in solid tumors. METHODS: Traditional hybridoma technology was used to prepare VEGF monoclonal antibodies (McAb); it's activity was measured by 3H-TdR incorporation on human umbilical vein endothelial cells (HUVEC). VEGF gene was amplified by PCR with cDNA as template from MGC803 cell lines. The PCR products were cloned into fusion protein prokaryotic expression vector PGEX2T which expressed in E. coli XL-1 blue. Western blot analysis was used to identify expression of VEGF. RESULTS: The McAbs could specifically bind to VEGF in ELISA. One of the McAbs(5C5) could neutralize the mitogenic activity of VEGF121 on HUVEC in a dose-dependent manner. The VEGF gene fragment obtained from RT-PCR cloned to PGEX2T vector expressed a protein product which reacted specifically with McAb 5C5. CONCLUSION: Gastric carcinoma is shown to express VEGF. It may be a major source of VEGF in human solid tumor. Monoclonal antibody against VEGF may be of value in the treatment of cancer. PMID- 11776867 TI - [Cloning and monoclonal antibody preparation of VEGF receptor KDR extracellular V VII domain and KDR expression in carcinomas of different origins]. AB - OBJECTIVE: To examine the expression of VEGF receptor KDR in carcinomas of different origins and provide possibility of exploring its relation to tumor growth and metastasis. METHODS: VEGF receptor KDR cDNA (V-VII) fragment was cloned from human umbilical vein with RT-PCR and expressed in E. coli Jm109. The purified GST-KDR fusion protein was used to immunize Balb/c mice and monoclonal antibody against KDR was prepared. With this monoclonal antibody, tumor tissue and related normal tissue of different origins were examined immunohistochemically for KDR expression. RESULTS: The frequency and intensity of KDR expression in different tumor tissues were obviously different. Transitional cell cancer of urinary bladder was 100% KDR positive and with highest intensity, while KDR expression in breast and intestinal adenocarcinoma was weaker and that in squamous-cell carcinoma of the lung was weakest. Moreover, KDR was also weakly expressed in other cells, such as smooth muscle cells and interstitial cells. CONCLUSION: VEGF receptor is expressed not only in the endothelial cells of tumor vasculature, but also in tumor cells. Tumor cell expression of KDR varies in intensity with tumors of different origins. The possible significance of VEGF receptor expression with regard to tumor cell proliferation and metastasis is discussed. PMID- 11776868 TI - [Effects of overexpression of p21WAF1/CIP1 on the malignant phenotype and apoptosis of human hepatocellular carcinoma cells]. AB - OBJECTIVE: To study the effects of overexpression of p21WAF1/CIP1 on the malignant phenotype and apoptosis of human hepatocellular carcinoma cells. METHODS: p21WAF1/CIP1 gene was transfected into a human hepatocellular carcinoma cell line, HCC-9204 with p53 mutation. Flow cytometry (FLC), transmission electron microscopy (EM) and DNA electrophoresis were used to identity apoptosis. RESULTS: The transfected HCC-9204 showed increase in cell number in G1 phase of cell cycle. Apoptosis was confirmed by the appearance of apoptotic peak on FLC, characteristic ultrastructural changes on EM and DNA laddering on electrophoresis. Apoptotic cells accounted for 22.5% of the total p21 transfected cells. An alteration of the malignant phenotype of cells was evidenced by the loss of anchorage-independent growth in soft agar and reduction BrdU incorporation. CONCLUSION: The results indicate that the p21WAF1/CIP1 can inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells with p53 mutation. PMID- 11776869 TI - [Type IV collagen and C-erbB-2 expression in oral candidal leukoplakia]. AB - OBJECTIVE: To investigate type IV collagen and C-erbB-2 expression in oral candidal leukoplakia. METHODS: 27 cases of oral candidal leukoplakia were studied by immunohistochemistry. RESULTS: In normal and simple hyperplastic epithelia type IV collagen was noted as brown linear staining along the basement membrane. The most obvious change in the staining pattern was that the linear staining became very thin or discontinued in dysplastic epithelia. C-erbB-2 was demonstrated in 25 cases(78%). The positive staining, as a reticular pattern, was located at cell membrane, and not correlated with epithelial dysplasia. CONCLUSION: The results indicate that type IV collagen expression changed in candidal leukoplakia with epithelial dysplasia. This kind of change may be related to basement membrane destruction. The immunohistochemically expression of C-erbB-2 has no correlation with epithelial dysplasia. PMID- 11776870 TI - [Study and detection of telomerase activity in oral squamous cell carcinomas and precancerous lesions]. AB - OBJECTIVE: To find out the expression of telomerase activity in oral squamous cell carcinomas (SCC) and oral precancerous lesions. METHODS: Telomerase activity was examined by telomerase PCR ELISA assay and telomere repeat amplification protocol (TRAP) electrophoresis. 60 fresh oral specimens were selected, including 20 oral SCC, 30 oral precancerous lesions (10 oral leukoplakia, LK, 20 oral lichen planus, LP) and 10 normal mucosa (NM). RESULTS: Telomerase activity detected in SCC (0.128) was highest among all of the tissues(LK: 0.054, LP: 0.0094, NM: 0.0014). Statistical difference was notable between SCC and LK, LP, NM (P < 0.01). A little difference was detected between LK, LP and NM. No difference was found between LK, and LP (P > 0.05). CONCLUSION: Telomerase may play an important role during oncogenesis of oral precancerous lesions, and may be a good molecular biomarker for observing the cancerization ability of precancerous lesion and estimating its prognosis. PMID- 11776871 TI - [The roles of oxygen free radicals and superoxide dismutase in the inflammatory injury in animal oral mucosa]. AB - OBJECTIVE: To study the roles of oxygen free radicals (OFRs) and superoxide dismutase (SOD) in the inflammatory injury in animal oral mucosa. METHODS: 1. The animal model was established in which an acute oral mucosal inflammation was induced by OFRs. Enzyme histological methods and biochemical methods were used respectively to investigate the activities of some important enzymes such as nicotinamide adenine dinucleotide phosphate-diaphorase and the amount of aminohexoses in the lesions; 2. Electron spin resonance and radioimmunoassay were ultilize respectively to study the effects of exogenous SOD on the amount of OFRs and prostaglandin E2(PGE2) in the lesions. RESULTS: 1. The activities of the enzymes in the oral lesions decreased and the amount of aminohexoses increased significantly; 2. Local administrating SOD could reduce the amount of OFRs and PGE2 in the lesions sufficiently. CONCLUSION: OFRs induced the inflammatory lesion by injuring some important enzymes and connective tissues in the oral mucosa. Local administrating SOD could scavenge OFRs and PGE2 in the oral mucosa sufficiently and reduce the degree of OFRs--induced oral mucosal inflammatory injury. PMID- 11776872 TI - [Evaluation of clinical value of technetium-99m(V) dimercaptosuccinic acid SPECT in diagnosis of parotid lump]. AB - OBJECTIVE: To evaluate the clinical value of single photon emission computed tomography (SPECT) on classifying parotid lump as benign or malignant before treatment. METHODS: SPECT images of the parotid region were obtained in forty five patients with parotid lump before surgery. We used technetium-99m(V) dimercaptosuccinic acid as imaging agent. The results were compared with their pathological diagnoses, clinical examination, and ultrasonography. RESULTS: The sensitivity, specificity and accuracy of Tc-99m(V)-DMSA SPECT imaging in determining malignancy of parotid lump were 93.7%, 72.4%, 80.0%, respectively. The uptake ratios of parotid lesions were higher in malignant tumors than benign tumors, cysts, and inflammatory lumps (P < 0.05). CONCLUSION: It is suggested that Tc-99m (V)-DMSA SPECT can be a useful aided method of preoperative diagnosis of parotid lumps. The uptake ratios can help increase the accuracy of diagnoses. For the benign tumors and inflammatory masses of parotid gland, the diagnoses had some false positives which may be reduced by combined clinical examination and ultrasonography. PMID- 11776873 TI - [Effect of unilateral condylar fracture on stress distribution in the mandible]. AB - OBJECTIVE: To investigate the effect of unilateral condylar fracture on stress distribution in the mandible in order to realize primarily the biomechanical mechanism of temporomandibular joint disorders (TMD) resulted in by joint injury. METHODS: The stress distributions in the mandible of a normal human and a patient with TMD induced by right condylar fracture following malposition healing were analyzed and compared quantitatively during centric occlusion by three dimensional finite element method. RESULTS: The patient contained the unbalanced stress distribution in the mandible, such as different nature and value of stress. The stress in the fractured side was higher than the non-fractured side, in which condyle is more evident. The maximum principal stress and minimum principal stress of each region in his mandible were much higher than that in a normal mandible. Its stress quality changes also. The stress in his mandible was distributed asymmetrically. CONCLUSION: Unilateral condylar fracture not only damaged its structure, but also induced the badness of its biomechanical environment, in which condyle was the most sensitive region during the stresses in the mandible were changed. It was preliminarily thought that unbalanced stress distribution, evidently increased stress and varied stress character were one of biomechanical mechanism of TMD. PMID- 11776874 TI - [Gingival crevicular fluid enzyme levels at different destruction sites in the same teeth]. AB - OBJECTIVE: To direct selecting proper sampling methods and sites in clinical research. METHODS: Gingival crevicular fluid (GCF) was sampled separately at the mesial-buccal and distal-buccal sites in the same teeth, which were destroyed differently. Clinical parameters were recorded in the subject sites and its adjacent sites. Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP) in the GCF were determined. Difference of the enzyme levels between the two sampling sites, and relations between the enzyme level and all the clinical parameters were assessed. RESULTS: GCF-AST, ALP per sample at severely diseased sites were much higher than that from healthy and/or mild sites in the same teeth. Significant positive correlation (P < 0.001, r > 0.5) was demonstrated between enzyme levels in the sampling sites and probing depth (PD) and attachment level (AL) of the lingual sites. However, there was mild significant correlation (P < 0.05, r = 0.275) between ALP level in the sampling sites and PD of the proximal-buccal sites of its adjacent teeth. No significant correlation (P > 0.05) was found between AST level in the sampling sites and PD, AL of the adjacent teeth sites, and also between ALP level in the sampling sites and AL of the adjacent teeth sites. CONCLUSION: Site-specificity of periodontal disease was further demonstrated. GCF components were influenced reciprocally more obviously in the same proximal than by other sites. PMID- 11776875 TI - [Relative analysis of the mRNA expression between endothelin and inducible nitric oxide synthase in pulpitis]. AB - OBJECTIVE: To study the relationship between endothelin-1(ET-1) and inducible nitric oxide synthase (iNOS) through the mRNA expression in pulpitis. METHODS: The model of experimental rat pulpitis; extraction of RNA, the reverse-polymerase chain reaction(RT-PCR) were used. RESULTS: The mRNA expression of ET-1/iNOS in pulpitis groups was higher than the control. There was relationship in the mRNA expression between ET-1 and iNOS. CONCLUSION: Pulp microcirculation was mechanized by the contraction and relaxtion of ET-1/iNOS, which could have direct effects on the pathological change. The control mechanism was due to the up regulation of ET-1/iNOS gene in transcription level. PMID- 11776876 TI - [Magnetic resonance imaging in dental appliance treatment of obstructive sleep apnea syndrome]. AB - OBJECTIVE: To investigate the upper airway changes after wearing dental appliance in obstructive sleep apnea syndrome(OSAS). METHODS: The research included 11 aged OSAS patients and 11 matched controls. Through dental appliance therapy the OSAS was proved by polysomnography to have ideal treatment results (AHI had decreased from 44.6 +/- 22.5 per hour to 7.53 +/- 6.44 per hour). Magnetic resonance imaging (MRI) had been performed before and after wearing dental appliance. The MRI images of upper airway after wearing dental appliance were compared with those of without wearing, and even with those of the controls. RESULTS: After wearing dental appliance the size of upper airway increased greatly, from 12.27 ml +/- 4.13 ml to 13.93 ml +/- 4.58 ml(P < 0.01), While the size of oropharynx was increased from 5.55 ml +/- 2.10 ml to 6.88 ml +/- 2.26 ml (P < 0.001). There was still remained significant difference at nasopharynx, soft palate and tongue compared with the matched controls. CONCLUSION: Dental appliance worked with the effect of enlarging upper airway. The abnormal airway morphology can not be changed completely by dental appliance treatment. MRI technique, especially the 3 D reconstruction model of upper airway, is an effective and special method in OSAS research. PMID- 11776877 TI - [A study of dental cast by using 3D laser non-contact measurement and analysis]. AB - OBJECTIVE: To research and develop a new scanning 3-D digitization system for noncontact measuring of dental cast. METHODS: By using two pulsate motor to make the synthetic movement of the dental cast, a special semiconductor laser and two special line-array CCD, the 3D coordinate could be gotten from the surface of the dental cast in any where. The program which is developed by Visual C++ language and run under the Windows surroundings can control the scanner, rebuild the 3D graphics and measure the coordinate of the dental cast. RESULTS: The system offers 70 mm x 70 mm x 70 mm measurement scope, 0.01 mm resoling power < 0.1 mm mean deviation, 25 mins for single cast scanning. CONCLUSION: This system provides many advantages such as in precision, simplicity, high efficiency, and wide range of measurement contents with complete direct view. It also supplied us some new functions which can not be done with traditional way of measurement. PMID- 11776878 TI - [A rat model of tongue mucosa squamous cell carcinoma induced by oral administration of 4NQO in drinking water]. AB - OBJECTIVE: To establish a more realistic animal model for oral carcinogenesis which reveals histological and immunological characteristics similar to the human counterpart. METHODS: 0.002% 4-nitroquinoline 1-oxide (4NQO) in drinking water was administered orally to SD rats for 9-32 weeks. Then the rats were killed and their tongues were removed for histological assessment. RESULTS: Gross changes included leukoplakia, erosion, ulcer and papillary appearance on the dorsum of the posterior tongue were present during carcinogenesis. Their corresponding histopathological findings ranged from hyperplasia (HP), mild-moderate dysplasia (mmDP), severe dysplasia (sDP) and in situ carcinoma (ISC) to well-differentiated invasive squamous cell carcinoma (SCC). The severity of lesions corresponded to the duration of administration. The tongues in rats treated with 4NQO for 9 weeks showed HP (80.0%) and mmDP (20.0%); those for 13 weeks showed mmDP (66.6%) and sDP (33.3%); those for 16 weeks showed sDP (55.5%) and ISC (44.4%); and those for 32 weeks showed sDP (12.5%), ISC (12.5%) and SCC (75.0%). The incidence of tongue cancer in rats treated with 4NQO for 9 weeks, 13 weeks, 16 weeks and then observed for 32 weeks was 50.0%, 62.5%, and 77.8%, respectively. No metastases were found. CONCLUSION: 4NQO reliably produced preneoplastic and neoplastic tongue mucosa lesions, which morphologically and histologically mimic human oral carcinogenesis. The rat tongue, a target organ of 4NQO, is not an immunologically privileged site like the hamster buccal pouch. Thus, the model should be appropriate to study molecular mechanism of neoplastic transformation and to assess new treatment modalities of premalignant and malignant lesions of the human oral cavity. PMID- 11776879 TI - [Pre- and post surgical orthodontic treatment of mandibular prognathism]. AB - OBJECTIVE: To analyze the patients we treated in clinic through combined orthodontic-orthognathic surgery, and get some guidance for the future clinical work. METHODS: All 40 skeletal Class III malocclusion patients we analyzed were from joint clinic of our hospital. They aged from 17 to 38. RESULTS: The duration for presurgical orthodontic treatment was 9 months on average (2-25 months), and for postsurgical orthodontic treatment about 7.6 months on average (2-15 months). The duration for whole active treatment was 16 months on average (4-41 months). The objectives of presurgical orthodontic are: Alignment of dental arches, decompensation of anterior and posterior teeth, leveling of arches, and coordination of the width of the upper and lower arches. After presurgical orthodontic treatment, most of the patients could be treated by one piece surgery, which could simplify the surgical procedure and reduce the relapse rate of surgery. During the surgery, we modified the intermaxilary fixation wires. We used rigid rectangular stainless steel wires with Edgewise appliances as the fixation wires instead of conventional canine and molar bands with multiloop wires. The aims of the postsurgical orthodontic treatment are: closing residual spacing, extrusion of posterior teeth for correction of local openbite in premolars region, paralleling of the teeth, and adjustment of occlusion. CONCLUSION: Pre- and post-ssurgical orthodontic treatment is essential to the surgical treatment for mandibular prognathism. PMID- 11776880 TI - [The comparison of bone densities of mandible and coxofemoral region between senile people with edentulous jaws and those with dentate jaws]. AB - OBJECTIVE: To observe if the senile people with edentulous jaws had lower bone dentilies of mandible and coxofemoral region than those with dentate jaws, and to find the systemic risk factors which were responsible for the tooth loss and the formation of edentulous jaws. METHODS: Two groups of senile people were selected. One group was edentulous and the other was dentate. All of them were examined by dual energy X-ray absorptiometry(DXA). RESULTS: The senile people with edentulous jaws had significantly lower bone densities of mandible(P < 0.001) and they also had lower bone densities of coxofemoral region than the dentate group people. CONCLUSION: It indicated that the decreased of bone densities of mandible and coxofemoral region was one of the systemic risk factors for tooth loss and the formation of edentulous jaws. PMID- 11776881 TI - [Relevance of Fc gamma R polymorphism to the susceptibility of early-onset periodontitis]. AB - OBJECTIVE: To investigate the polymorphism of the Fc gamma R genotype and its association with the susceptibility of early-onset periodontitis (EOP). METHODS: DNA of the white blood cells from 33 subjects with EOP and 27 healthy controls was extracted. Genotypes of the Fc gamma RIIA and Fc gamma RIIIB were determined by PCR followed by BstUI restriction endonuclease digestion and DNA sequencing, respectively. Then compared the differences in distribution of each genotype. RESULTS: No statistical difference in distribution of Fc gamma RIIA was observed between patients and controls. However, a significant over-representation of the Fc gamma RIIIB NA1/NA1 was found in EOP. CONCLUSION: These results suggest that the Fc gamma RIIIB NA1/NA1 may be a risk indicator for the susceptibility of the EOP. PMID- 11776882 TI - [Cloning and partially sequencing of mouse dentin sialophosphoprotein encoding mature protein]. AB - OBJECTIVE: Cloning and partially sequencing of mouse dentin sialophosphoprotein (DSPP) encoding mature protein. METHODS: Total RNA was extracted from the tooth germs of newborn mouse by acid guanidinium thiocyanata-phenol-chloroform method, the desired DNA product was obtained from the total RNA by RT-PCR with the primers including Oligo(dt) and two gene specific primers. The segment (about 3 Kbp) was inserted into pBluescript vector and the interesting plasmid was transformed into E. Coli host strain XL1-Blue. The double-stranded DNA of the positive clone was analyzed by restriction endonuclease mapping and DNA sequencing. RESULTS: The restriction endonuclease map and sequence of mouse DSPP encoding mature protein were consistent with those of the published. CONCLUSION: The mouse DSPP cDNA encoding mature protein was obtained for further study. PMID- 11776883 TI - [Comparison of closing T loop technique and sliding technique using preadjusted appliance]. AB - OBJECTIVE: To compare the difference between closing T loop technique and sliding technique. In anchorage demand and treatment outcome. METHODS: Sixteen first premolar extraction cases were chosen and divided into two groups for prospective paired t-test. They were treated by one author using 0.022" x 0.028" preadjusted appliances. T loops were fabricated using 0.018" x 0.025" s.s. wire. Chinese NiTi coil springs and 0.019" x 0.025" s.s. arch wire were employed in sliding technique group. Treatment materials, steps and appliance design in both groups were standardized. Measurements of dental model and cephalogram were taken. RESULTS: In closing T loop technique group and sliding technique group, the ratio of anterior teeth movement was 0.55 and 0.53 respectively. The difference was not significant (P > 0.05). L1MP angle decreased by 5.7 degrees and 3.1 degrees respectively during treatment (P < 0.05). CONCLUSION: Demand on anchorage was not significantly different between two groups. Sliding technique was more favorable in maintaining anterior teeth inclination. PMID- 11776884 TI - [A study of the maximal mouth opening movement of normal subjects]. AB - OBJECTIVE: The aim of this paper was to study condyle movement and the relation between it and incisor movement when the subjects performed maximal open-closed movement. METHODS: 38 normal students were tested by a six degrees of freedom mandibular movement recorder MT-1602. The traces and velocity curves of the condyle movement were analized on the horizontal plane. RESULTS: (1) The horizontal traces of condyle movements included straight line and smooth curve. (2) The velocity curve was like triangle. Acceleration was constant before and behind the peak respectively. (3) Unequal velocity of the bilateral condyles was common. (4) The appearances of traces correlated with the beginning relative horizontal velocity of bilateral condyles. The tracing vector was inclined to the rapid side. (5) The incisor pathway was affected by both the relative horizontal velocity and the corresponding horizontal trace of the bilateral condyles. CONCLUSION: The movement of condyle were adaptable to the stomatognathic system. PMID- 11776885 TI - [Problems and prospects in porcelain restoration in China]. PMID- 11776886 TI - [Analysis of the oxide film of Ni-Cr porcelain alloy]. AB - OBJECTIVE: In order to find out the causes of cervical gray line of PFM crown, the features of oxide film of Ni-Cr alloy were investigated. METHODS: 1. The phases were analyzed using x-ray radiation shield. 2. Compositions of oxide film and base metal were measured using electronic scanning microscope. 3. The thickness of oxide film and the variations of Ni, Cr, O in oxide film were evaluated using Auger electron spectroscope. RESULTS: 1. There were not only NiCr2O4 but also Cr2O3, SiO2, and gamma phase solid solution in the surface. 2. The weight contents of Cr and Si were higher while Ni was lower in oxide film than in the base. 3. Oxide film became much thicker(400 nm: 16 nm) after the temperature cycling. CONCLUSION: The medium-thicked oxide film was formed after baking, and it was not a complete film. PMID- 11776887 TI - [Study of low-fusing porcelain fused to Ti-75 alloy]. AB - OBJECTIVE: To study the feasibility of low-fusing porcelain fused to Ti-75 alloy. METHODS: The bond strength and interfacial state of porcelain-titanium were observed by EPM analysis and shear test. RESULTS: The results showed that the shear bond strength of low-fusing porcelain fused with Ti-75 alloy and the conventional porcelain fused to base metal alloy (NC-VMK68) respectively were 47.38 +/- 7.95 MPa and 48.50 +/- 7.60 MPa. There were no significant difference in the shear bond strength between the two results (P > 0.05). The analysis of electron microprobe showed that there was no crack in the interface, the low fusing porcelain permeated Ti-75 alloy fairly, and titanium diffused from Ti-75 alloy to porcelain, and silicon, stannum diffused from porcelain to Ti-75 alloy. CONCLUSION: Ti-75 alloy can be regarded as a suitable alloy for low-fusing porcelain. PMID- 11776888 TI - [Arthrocentesis and lavage of TMJ for the treatment of anterior disc displacement without reduction]. AB - OBJECTIVE: To evaluate the clinical efficacy of the TMJ arthrocentesis and lavage as a treatment for anterior disc displacement without reduction of the TMJ. METHODS: 38 patients with limited mouth opening caused by anterior disc displacement without reduction were treated by using TMJ arthrocentesis and lavage. Clinical data including pain and mandibular motion were collected and then analyzed. Arthrography was used to evaluate disc position. RESULTS: The mandibular motion had increased significantly (P < 0.001) at different period of time, especially within 1 month. Jaw pain had also significantly improved (P < 0.01). Arthrography revealed that most of the TMJs studied had persistent anterior disc displacement with only 2 patients demonstrating a "reduced disc". CONCLUSION: Arthrocentesis and lavage is effective in reducing pain and increasing mandibular motion in patients with anterior disc displacement without reduction, especially in patients the duration of symptoms being less then 6 months. It is recommended as a simple alternative to more invasive TMJ procedures. PMID- 11776889 TI - [Treatment of class II furcation involvement: guided tissue regeneration with atelocollagen membrane]. AB - OBJECTIVE: To evaluate the effectiveness of guided tissue regeneration (GTR) on class II furcation involvement with absorbable atelocollagen membranes made in China. METHODS: GTR was performed on 26 sites with class II furcation defect in 17 patients. Clinical measurements and digital subtraction radiography were used to evaluate the effect. RESULTS: Clinical measurements showed significant attachment gain, significant decrease of probing depth (PD) and horizontal probing depth (HPD) at 3, 6, and 12 month after surgery. The mean reduction of HPD were 1.8 mm, 2.2 mm, 2.5 mm at 3 month (23 sites), 6 month (12 sites), and 12 month (6 sites) after surgery respectively. PD decreased by 1.22 mm, 1.56 mm and 1.75 mm. Attachment gained by 1.17 mm, 2.11 mm and 1.75 mm. Three sites showed complete defect fill during 3 to 12 months after surgery. Only 1 mm or less could be probed horizontally in another 4 furcation lesions during 3 to 12 months post operation. The HPD of pre-operation in these 7 cases were 2.0 mm to 4.0 mm, and the bone defects observed during surgery were smaller in these cases than in other cases. The other 19 furcation involvement improved significantly. The result of digital subtraction radiography showed that increase of bone density was found at 2 months after surgery. The amount of bone gain increased with time. The areas of increased bone density were 0.3-25.7 mm2 in 13 teeth. CONCLUSION: The class II furcation involvement can be treated by GTR with absorbable atelocollagen membranes with good results. PMID- 11776890 TI - [Basal cell adenocarcinoma of the salivary gland: a clinicopathologic study of 14 cases]. AB - OBJECTIVE: To study clinicopathologic features and behaviour of the basal cell adenocarcinoma of salivary gland tumor and prognosis of the patients, METHODS: 14 cases with basal cell adenocarcinoma were studied clinicopathologically. RESULTS: The clinical features were as follows: females more than males; most frequently in the minor salivary glands; 21.4% of cervical lymph node metastasis and 14.3% of distant metastasis; and rather poor prognosis. The histopathologic appearances were similar to those of basal cell adenoma, but with more mitotic figures and infiltrating growth. CONCLUSION: This tumor was of moderate grade malignancy. It must be treated radically. The elective neck dissection could be considered for the patients with extensive tumors. PMID- 11776891 TI - [Local expresion of proinflammatory cytokines in maxillofacial gunshot wound]. AB - OBJECTIVE: To study the relationship between proinflammentory cytokines and wound healing in local area. METHODS: Interleukin(IL)-6, IL-8 and tumor necrosis factor alpha (TNF-alpha) expression in local soft tissues after lower jaw gunshot wound were assessed by using immunohisto-chemistry, and pathological methods. RESULTS: High expressions of these cytokines were observed in local soft tissues of wounds after the gunshot. The cytokines expressions were different between the area near the bullet path and that far from the path. There was only one peak of the cytokines concentrations in the area far from the bullet path, while there were two peaks of the cytokines concentrations in the area near the bullet path, specially IL-6, IL-8. There were time differences for some different cytokines to reach the peaks of the their concentrations. In wound situ, the fibroblasts, mononuclear phagocytes and endothelial cells expressed IL-6, IL-8 and TNF-alpha after the firearm. CONCLUSION: These results suggest that proinflammatory cytokines play an important role in regulating inflammatory cytokine reactions of local injury tissues. They might improve the functions of fibroblasts, mononuclear phagocytes and endothelial cells and stimulate wound cells to produce and release other cytokines. PMID- 11776892 TI - [Three dimensional finite element analysis of effects on composite resin for filling in various cavity margin design]. AB - OBJECTIVE: To evaluate the stress distribution of different angles of cavity margins with composite resin filling. METHODS: The stress distributions of different angles of cavity margins of class I cavity of molars were analyzed by the method of three dimensional finite element. The cavity was filled with composite resin and the stress vertical force and lateral force was calculated. RESULTS: In the 5 designed different cavity margin angles, the vertical forces and lateral forces were 18.757 MPa and 22.309 MPa respectively when the angle is 90 degrees; when the angles were 75 degrees and 60 degrees, they were 10.580 MPa, 14.265 MPa and 9.025 MPa, 13.230 MPa respectively. The vertical forces and lateral forces produced by the surface of composite resin while being stressed were up to 18.757 MPa and 22.309 MPa. The forces of the second layer evidently reduced to 2.586 MPa and 6.8 MPa. CONCLUSION: When fill the molars with resin in clinic, the angles of cavity margins should be prepared with the slopes of 60 degrees to 75 degrees. PMID- 11776893 TI - [The ultrastructure of membrane component in adenoid cystic carcinoma of salivary gland]. AB - OBJECTIVE: To study morphological variations of basment membrane component (BMC) for determination of invasion and vascular metastasis in adenoid cystic carcinoma (ACC). METHODS: The BMC of 8 cases in ACC and 2 cases of normal parotid gland were observed by LM and EM. RESULTS: The BMC surrounding tumor mass and strands showed multi-layered or dissolution, pseudopodia were seen extended from tumor cells, and contained numerous microvesicles. If the tumor cell attached blood vessels, the collagenous fibril were dissoluted and BMC were lost. CONCLUSION: The tumor cell may release some digestive enzymes which may be able to dissolve BMC and collagenous fibrils and invade into blood vessels and metastasis take place. PMID- 11776894 TI - [Alteration of CD44v3 and CD44v6 expression in oral premalignant epithelia]. AB - OBJECTIVE: To investigate the expression of CD44v3 and CD44v6 in oral premalignant epithelia and its relationship to the carcinogenesis of oral mucosa. METHODS: 85 normal, hyperplastic, dysplastic and malignant oral epithelia were studied by immunohistochemistry. RESULTS: Normal and hyperplastic epithelia showed strong CD44v3, v6 staining on cell membrane. Cells in the deep layers of moderate and severe dysplastic epithelia showed remarkably reduced staining intensity or no positive staining as compared with normal and hyperplastic epithelia. This down-regulation of CD44v3, v6 expression was noted in all 12 cases of severe dysplasia. In invasive front of squamous cell carcinoma and some metastases to lymphnode CD44v3 and v6 staining were also weak or negative. CONCLUSION: Low level expression of CD44v3 and v6 exists in moderate and severe epithelial dysplasia. This may be related to the reduction of cellular adhesion and thereby facilitates the infiltration of basement membrane by dysplastic cells. PMID- 11776895 TI - [Expression of C-erbB-2 oncogene mRNA in salivary gland tumors]. AB - OBJECTIVE: To study relationship of C-erb-2 oncogene mRNA expression and histotype, tumorigenesis and biological behavior of salivary gland neoplasms. METHODS: Using 32P labeled oligonucleotide as probe, the dot blot technique was used to study the expression of C-erbB-2 oncogene mRNA in salivary gland neoplasm with normal salivary gland as control. RESULTS: With the expression in normal salivary gland as a standard, low C-erbB-2 mRNA expression was seen in adenolymphoma, basal cell adenoma. However, various degrees of over-expression of C-erbB-2 oncogene mRNA were detected in pleomorphic adenoma, mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, papillary cystic carcinoma, and myoethelial cell carcinoma. CONCLUSION: C-erbB-2 oncogene mRNA over-expression in salivary gland neoplasm is related to biological behavior of salivary gland carcinoma. PMID- 11776896 TI - [Expression of metastasis suppressor gene nm23-H1 in oral squamous cell carcinoma and its relation to tumor prognosis]. AB - OBJECTIVE: To study the relation between the expression level of nm23-H1 protein and prognosis of oral squamous cell carcinoma (OSCC). METHODS: The expression of nm23-H1 protein in 75 cases of OSCC, 27 cases of oral mucosa, 9 cases of cervical lymph-node metastases by immunohistochemical technique (SABC), and the relation between nm23-H1 protein expression level and prognosis of OSCC was evaluated by chi-test and single-factor, multi-factor Cox proportional hazards regression model analysis. RESULTS: These immunoreactivities of nm23-H1 protein were mostly in the cytoplasm of tumor and epithelial cells. There was a significant difference of nm23-H1 protein expression level between three-year survival and seven-year survival group (P < 0.05), and there was a relation between nm23-H1 protein expression level and prognosis of OSCC in single-factor Cox analysis. But no relation was found between nm23-H1 protein expression level and prognosis in multi-factor Cox analysis. CONCLUSION: nm23-H1 protein expression level was probably not a valuable predictor of OSCC patients' prognosis. It may indirectly affect OSCC prognosis through its effect on OSCC metastasis. PMID- 11776897 TI - [Experimental study on the effect of restorative dentin formation with human dentin phosphoprotein in immature permanent teeth of minipig]. AB - OBJECTIVE: To investigate the function of human dentin phosphoprotein(DPP) on dentine mineralization in vivo. METHODS: Pulp capping with human DPP was made in the permanent teeth of minipigs with calcium hydroxide and zinc oxide eugenol cement as controls. The minipigs were sacrificed at intervals of 14, 30, 90 days respectively after operation. RESULTS: The histopathological results revealed that pulp cells had developed into odontoblastoid cells around the major restorative dentin body after two weeks. There was complete restorative dentin bridge a month later. The bridge became thick and dense, and mainly was tubular dentin in 3 month. There were well developed odontoblasts under the bridge. In the calcium hydroxide capping group, inflammatory cytonecrosis zone was found in the surface of dental pulp and only a little calcial bodies formed in two weeks. Complete restorative dentin bridge was formed in 1 to 3 months, the speed of dentin bridge formation was not as quick as that of DPP group. CONCLUSION: DPP can induce pulp cells to develop into odontoblasts and formation of dentin bridge with little stimulation to the dental pulp. This study suggests that DPP plays an important role in the biomineralization of dentin development and restoration. PMID- 11776898 TI - [p53 gene mutation determined by single-strand conformational polymorphism and DNA sequencing analysis in pleomorphic adenoma of salivary gland]. AB - OBJECTIVE: To detect p53 exon 6 mutation pattern in pleomorphic adenoma of salivary gland. METHODS: Single-strand conformational polymorphism (SSCP) and DNA sequecing were used. RESULTS: SSCP analysis showed that 6 of 11 cases with SSCP positive were exon 6 abnormal. Comparison of the SSCP results with DNA sequecing, 4 cases with p53 exon 6 mutations were SSCP positive. Mutation pattern included base substitution (point mutation, G-->T, T-->G) and frame-shift mutation (base insertion and base loss). CONCLUSION: Poly-codon and poly-pattern mutations appeared in p53 exon 6. PCR-SSCP was a convenient method to detecte gene mutation. PMID- 11776899 TI - [Prosthodontic treatment of secondary occlusal and maxillofacial deformities of postoperative cleft lip and palate]. AB - OBJECTIVE: To investigate the kind and degree of deformtive and the charactertics and effects of prosthetic treatment in patients with secondary maxillofacial deformities after cleft lip and palate operation at early age. METHODS: Clinical examinations and cephalometric analysis were performed in 30 patients. RESULTS: The results showed that prosthetic treatment can improve facial form and oral functions a great deal but with limitations. CONCLUSION: Prosthetic treatment should be considered as an essential part in serial therapy of cleft lip and palate. PMID- 11776901 TI - [The measurement and expression about tooth color]. PMID- 11776900 TI - [Studies on the spectrum features of nasalized vowels]. AB - OBJECTIVE: To study the spectrum features of nasalized vowels and set up effective indexes to reflect the features. METHODS: The acoustic features of 100 children's speech, aged 5 to 12 years old, consisted of 40 unrepaired cleft palate children, 28 VPI children and 32 normal children, were studied by the application of digital spectrograph. RESULTS: No significant changes in the frequency of inherent formants of each vowel, appearance of one relatively fixed extra formant in the low frequency area, and the energy of high frequency area being damped obviously were the main spectrum features of nasalized vowels. CONCLUSION: There are three main features on the spectrums of nasalized vowels compared to that of oral vowels. Nasal resonance index (NRI) can effectively distinguish the extra formant in low frequency area of oral vowel /a/ from nasalized vowel /a/. Energy damping index (EDI) can effectively reflect that the energy of high frequency area of each nasalized vowel is damped obviously. PMID- 11776902 TI - [Current and future of oral maxillofac surgery in China]. PMID- 11776903 TI - [Cervical management in the N0 squamous cell carcinoma of the tongue]. AB - OBJECTIVE: To assess whether the elective neck dissection would be beneficial as a routine management in the N0 squamous cell carcinoma of the tongue. METHODS: Cox regression model was used for analysis of tongue cancer cases treated by our hospital in a period from 1958 to 1996. RESULTS: Size of primary tumor and preoperative radiation showed significant difference in relation to cervical lymph node recurrence or metastasis. Neck dissection in the series was not a factor to influence the rate of cervical recurrence or survival. 5-years survival was 73.5% versus 69.3% in patients who underwent elective neck dissection and those without neck dissection (difference not statistically significant). CONCLUSION: We suggest that elective neck dissection would be avoided in T1 or T2 patients who have no neck node metastases. PMID- 11776904 TI - [Development of partially sintered alumina block for dental CAD/CAM and mechanical properties testing]. AB - OBJECTIVE: It is a new way to fabricate all ceramic crowns by combining dental CAD/CAM with glass infiltration technology. METHODS: A partially alumina sintered block made of a high purity, fine alumina powder was shaped by isostastic pressure and sintered at 1,400 degrees C. Its mechanical properties were tested and microstructure was observed by SEM. RESULTS: The Vicker's hardness, three point bending strength, fracture toughness of partially sintered alumina block were 1.65 MPa, 210 MPa, 1.90 MPam1/2 respectively. Micrographs of SEM indicated that partially sintered alumina contained the structure of continuous three dimensional open pores through the neck growth and surface diffusion of the interparticles. CONCLUSION: The partially sintered alumina block that developed in this way may be used to mill for CAD/CAM and fabricate the shrinkage-free all ceramic crown. PMID- 11776905 TI - [Long-term complications associated with immediate plate reconstruction for mandibular defect following tumor-surgery]. AB - OBJECTIVE: To assess the long-term complications associated with the application of reconstruction plate. METHODS: Ninety-seven patients underwent immediate repair by using bendable reconstruction plate for maintainance of space and contour following mandibular segmental resection. Of them, 68 cases were followed up for the final outcomes. RESULTS: Skin or mucosa perforation occurred 6 cases, instabilization of screws in 22 cases, and broken of plate in 3 cases. The reasons for skin or mucosa perforation was possibly associated with circulatory disturbance due to postoperative irradiation. The bone absorption and screw loosening occured most frequently in bone defect involving mandibular angle and chin. CONCLUSION: High concentration of unrationable stress and irradiation were recognised to be the factors responsible for the perforation of covering tissue and screw loosening. The broken of plate was brought about possibly by stress loading and fatigue weakness of plates. PMID- 11776906 TI - [CT findings of non-Hodgkin lymphoma in the head and neck]. AB - OBJECTIVE: To evaluate the characteristic CT findings of non-Hodgkin lymphoma (NHL) in head and neck. METHODS: Thirty-six patients with the head and neck NHL consisted of 23 males and 13 females, median 49.2 years. All cases were categorized into two groups: extranodal and nodal NHL lesions. RESULTS: The extranodal NHL disease included 39 lesions (31 cases), and, the frequent head and neck sites of such lesions were Waldeyer's ring (n = 11), maxilla (n = 8), maxillofacial spaces (n = 7), salivery gland (n = 6), and others (n = 7). 30 lesions were soft tissue mass; 9 were mucosal thickening abnormality (including Waldeyer's ring in 6 lesions, maxilla in 2 lesions, and nasal cavity in one lesion). The majority of such extranodal NHL diseases were demonstrated on CT as non-necrosis (33 lesions) and uneven margin (26 lesions). Sixteen lymph node NHL lesions were composed of 6 NHL confined to neck lymph nodes and 10 combinations of nodal and extranodal NHL diseases. 5/6 of the former had the condition with rim enhancement, necrosis and confluent nodal mass. Of ten of the latter, 7 had the necrostic lesion with rim enhancement, and 3 had the lesion with confluent nodal mass. CONCLUSION: Multiple maxillofacial extranodal sites of soft tissue mass with the presence of non-necrosis and uneven margin should be considered as the characteristic sign of NHL disease in the head and neck. Most nodal NHL may have the lesion with necrosis and rim enhancement, and the confluent mass is commonly seen in NHL confined to the neck lymph nodes. PMID- 11776907 TI - [Evaluation of Wits appraisal with superimposition method]. AB - OBJECTIVE: To compare the conventional Wits appraisal with superimposed Wits appraisal in evaluation of sagittal jaw relationship change between pre and post orthodontic treatment. METHODS: The sample consists of 48-case pre and post treatment lateral head films. Computerized digitizing is used to get the cephalometric landmarks and measure conventional Wits value, superimposed Wits value and ANB angle. The correlation analysis among these three measures was done by SAS statistical package. RESULTS: The change of ANB angle has higher correlation with the change of superimposed Wits than that of the conventional Wits. The r-value is as high as 0.849 (P < 0.001). CONCLUSION: The superimposed Wits appraisal reflects the change of sagittal jaw relationship more objectively than the conventional one. PMID- 11776908 TI - [Infiltration of monocytes/macrophages and expression of monocyte chemoattractant protein-1 in gingival tissues from patients with rapidly progressive periodontitis]. AB - OBJECTIVE: To find if there was any difference in monocytes/macrophages infiltration and monocyte chemoattractant protein-1(MCP-1) expression between rapidly progressive periodontitis (RPP) and adult periodontitis (AP) tissues. METHODS: Inflamed gingival specimens (20) were obtained from RPP(14) and AP(6) patients, and specimens from clinically healthy subjects (H,6) as control. The monocytes/macrophages and MCP-1 expression were detected by immuno-histochemistry SP assay with antibodies against CD14 and CD68, and rabbit anti-MCP-1 antibody. RESULTS: There were no differences in the mean counts (+/- SD) of monocytes/macrophages and MCP-1 positive cells between RPP and AP groups. CONCLUSION: Though rapid and severe periodontal destruction occurs in RPP, there is no differences in monocytes/macrophages infiltration and MCP-1 expression in gingival tissues between rapidly progressive periodontitis and adult periodontitis patients. PMID- 11776909 TI - [The influence of nerve growth factor on inferior alveolar nerves regeneration in the silicone tubes]. AB - OBJECTIVE: To explore the effect of exogenous nerve growth factor(NGF) in the regeneration of adult white rabbits inferior alveolar nerve within the silicone tubes. METHODS: In 24 adults white rabbits. A bilateral 8 mm inferior alveolar nerve gaps were created, and the proximal and distal stumps were inserted into a 12 mm silicone tube. The silicone tube of the right side was filled with exogenous NGF(experimental group) and the contralateral side was filled with saline (control group). Regeneration of the nerves was assessed by histological exam and nerve electrophysiological appreciation. Total number of the regenerating myelinated nerve fibers, the conduction velocities of nerves the thickness of myelin sheaths and the cross section area of myelinated nerve fibers between the experimental and the control groups were compared. RESULTS: The results showed that: 1. The experimental groups demonstrated more myelinated nerve fibers than that of the controls in 12 and 18 weeks. 2. At the same time following surgery, the myelin sheath thickness and the cross section area of myelinated nerves in the experimental groups were significantly greater than that in the controls. 3. In 12 and 18 weeks, the conduction velocities of regenerating nerves in the experimental groups were faster than that of the controls. CONCLUSION: This study suggested that exogenous NGF can enhance regeneration of inferior alveolar nerve with necovery of its sensory function. PMID- 11776910 TI - [A light and scanning electron microscopic study of primary teeth in hypophosphatasia]. AB - OBJECTIVE: To investigate the features of primary tooth structure in hypophosphatasia. METHODS: Three primary teeth from two patients at age of 3 yr-6 month and 4 yr-2 month, who were diagnosed hypophosphatasia. The structural changes of these teeth were examined by light microscopy, polarizing microscopy and scanning electron microscopy. RESULTS: The complete absence of cementum was a prominent feature in all the teeth, three small island-shape cementun areas were found in scanning electron microscopy. A large number of resorptions were found on the root surfaces, particularly near apical portions of roots. The main findings included disturbances of dentin mineralization, hypoplasia or aplasia of root cementum and external resorption of root dentin. CONCLUSION: The hypoplasia or aplasia of root cementum was thought to be the prime etiological factor in the early loss of primary teeth. PMID- 11776911 TI - [Histomorphometry of silicon nitride composite endosteal implant in dogs]. AB - OBJECTIVE: To study the dynamic changes of bone interface with silicon nitride (Si3N4) composite implants. METHODS: 4 Beagle dogs were experimental animals, Si3N4-HA and pure Si3N4 implant were experimental group, and Ti and Ti-HA were used as comparisons. They were implanted into dogs' femurs by stages. Histomorphometry was used to analyse and compare bone growth metabolism of bone interface with implant as well as evaluation of biocompatibility from quantitative and dynamic aspects. RESULTS: Parameters expressing mineralization and speed of deposition at the Si3N4-HA bone interface were higher than comparisions' at the first month. After 6 months, pure Si3N4's bone histomorphometic parameters had no notable difference with others. CONCLUSION: New implant material is useful to the clinic. The histomorphometry is of much value for the study of interface bone metabolism from quantitative and dynamic point of view. PMID- 11776912 TI - [A study of clinicopathology and lectin immunohistochemistry in unicystic ameloblastoma]. AB - OBJECTIVE: To investigate clinicopathological characteristics of unicystic ameloblastoma and histological markers for differential diagnosis with odontogenic cyst. METHODS: HE staining and histopathological observation, and lectin UEA-1, BSA-1 immunohistochemistry staining. RESULTS: 40 cases of unicystic ameloblastoma were divided histologically into 3 groups. In odontogenic cysts, most of epithelial lining showed positive binding with UEA-1 and BSA-1, whereas negative reactions were obtained for these two lectins in the epithelial components of unicystic ameloblastoma and solid or multicystic ameloblastoma, except for limited UEA-1 or BSA-1 binding to markedly keratinized tumor cells in several cases of ameloblastomas. CONCLUSION: The unicystic ameloblastoma is a distinct entity which has characteristic clinicopathology. The lectin staining for UEA-1 and BSA-1 is a useful histological aid to differential diagnosis between unicystic ameloblastoma and odontogenic cyst. PMID- 11776913 TI - [Quantitative analysis of thirty-one elements in the stained dental fluorosis of enamel]. AB - OBJECTIVE: To study the relationship between concentrations of thirty elements and fluorine element in teeth with stained dental fluorosis from high fluoride water area and teeth from normal fluoride area. METHODS: The concentration of thirty-one elements in 43 teeth was measured by plasmatron spectrographic analysis and fluoride selective electrode. RESULTS: 1. Content of F, P, Ca, Mn, As, Se, Al, Ti, Mo, B elements in enamel had a direct relationship to severity of enamel staining. 2. Content of Mn, As, Se, Sr, Nb, Ca, P elements were high positively related to content of fluorine in enamel (P < 0.05). CONCLUSION: Mn, As, Se, F content is closely related to the pigment formation in dental fluorosis of enamel. PMID- 11776914 TI - [Apoptosis in the developing tooth of postnatal rat]. AB - OBJECTIVE: To study apoptosis in the developing tooth of postnatal rat. METHODS: Transferase-mediated, dUTP-biotin nick end labeling(TUNEL) method was utilized to label the paraffin sections of the lower and upper jaws taken from 3 days and 9 days of postnatal rats. RESULTS: Positive stains for the presence of apoptosis were observed in ameloblasts, especially in cervical loop region, and stellate reticulum cells. Odontoblasts at the tip of developing molars in which physiological osteodentin was forming were strongly positive. A few dental pulp cells were labeled. CONCLUSION: Apotosis is a biological process, which play an important role in the formation of teeth. Apoptosis may take place in epithelial derived cells as well as mesenchymal-derived cells. PMID- 11776915 TI - [The abnormal expression of pRb during DMBA-induced hamster buccal pouch carcinogenesis]. AB - OBJECTIVE: To study the expression and role of pRb in 7,12 dimethylbenzanthracene(DMBA) induced hamster buccal pouch carcinogenesis. METHODS: DMBA (0.5%) in acetone was applied to the right buccal pouch 3 times per week for up to 12 week. Paraffin-embedded sections were used for pRb immunohistochemical determination (ISAB technipue, polyclonal antibody c-15 for pRb). The density of staining was analysed by rank sum test. RESULTS: The positive staining of pRb was strong in normal buccal epithelium, no alteration of pRb staining in 3 week (hyperplastic epithelium) and somewhat reduced between 6 and 9 week (dysplastic lesion), but it was marked reduced in 12 week (carcinoma). Statistical analysis found that changes of pRb were associated with stages of carcinogenesis. CONCLUSION: These results indicate that abnomal expression of Rb gene product could be related to oral carcinogenesis and may serve as a biomarker for supervising oral malignancy. PMID- 11776916 TI - [Quantitive study of 6-keto-prostaglandin F1 alpha and thromboxane B2 in human pulp]. AB - OBJECTIVE: To study the change of the levels of 6-keto-prostaglandin F1 alpha (6 K-PGF1 alpha) and thromboxane B2 (TXB2) in deep caries and pulpitis pulp. METHODS: The levels of 6-K-PGF1 alpha and TXB2 were determined by radioimmunoassay (RIA) in 44 pulp tissues from subjects with healthy pulp (H), deep caries (DC), chronic pulpitis (CP) and acute pulpitis(AP). The 6-K-PGF1 alpha/TXB2 ratio(K/T) was calculated. RESULTS: The lconcentrations of 6-K-PGF1 alpha in Group AP were highest and those in Group H were lowest. The levels of TXB2 in Group DC were lower than Group CP and those in Group H were lowest. Significant differences in K/T ratio were found among the groups except those between Group H and DC. The value of Group AP was highest and that of Group CP was lowest. CONCLUSION: The dysbolism and dysequilibrium of PGI2 and TXA2 may be closely related to the genesis of pulp diseases. PMID- 11776917 TI - [The effects of basic fibroblast growth factor on proliferation and differentiation of human dental pulp cells in vitro]. AB - OBJECTIVE: To evaluate the effects of human basic fibroblast growth factor (hbFGF) on proliferation and differentiation of human dental pulp cells in vitro. METHODS: The syntheses of DNA, collagen, fibronection (FN), alkaline phosphatase (ALP) and bone morphogenetic protein (BMP), and the expression of agglutinin were measured with imagine processing and analysis system. RESULTS: hbFGF at concentration of 1-10 micrograms/L stimulated the cell proliferation measured by MTT colorimetric assay, and promoted incorporation of 3H-thymidine at 1-100 micrograms/L. The expression of type I collagen, FN, Con A receptor, and ALP significantly increased at hbFGF concentration of 10-1,000 micrograms/L, but the expression of type III collagen and WGA receptor markedly decreased at the same concentration. There was no significant difference in expression of BMP. CONCLUSION: bFGF has the capability to promote the differentiation of dental pulp cells to odontoblasts in culture. PMID- 11776918 TI - [The changes of transforming growth factor beta 1 in periodontal tissue during orthodontic tooth movement]. AB - OBJECTIVE: To observe the distribution and change of transforming growth factor beta 1 (TGF-beta 1) in periodontal tissue and understand the role of TGF-beta 1 in orthodontic tooth movement. METHODS: Apply force on right maxillary first molars in rats, and examine the decalcified alveolodental connected tissue in different stage of tooth movement with immunohistochemical staining technique (SP method). RESULTS: TGF-beta 1 exists in normal periodontal tissue. The expression of it in periodontium increases during orthodontic tooth movement. Especially from 5 to 10 days after force application, the expression at tension side is much more than those at pressure side. CONCLUSION: TGF-beta 1 plays an important role in remodeling of periodontal tissue during orthodontic tooth movement, and can powerfully promote bone formation. PMID- 11776919 TI - [Surgical reduction of condylar fracture using lag screw]. AB - OBJECTIVE: To evaluate the feasibility and result of application of lag screw osteosynthesis in condylar fracture. METHODS: Six dislocated condylar fractures were treated with lag screw. Postoperative follow-up mean 7 months (range 3-13 months). RESULTS: It showed no complaint on TMJ area from patients during the follow up, no facial asymmetry was found, no patient had malocclusion, 5 patients had mouth opening over 40 mm 3 months postoperatively, and all patients were satisfied with the treatment results. CONCLUSION: Based on the clinical and radiological results the authers believe that lag screw technique is a feasible method for indicated condylar fracture. PMID- 11776920 TI - [Craniofacial resection for advanced malignant tumors in oral and maxillofacial region]. AB - OBJECTIVE: To investigate the clinical significance of craniofacial resection for advanced malignant tumors of OMS region. METHODS: Forty-six patients underwent craniofacial resection for malignancies involving the anterior and middle cranial fossa over a 20-year period between June 1978 and December 1997 in our department were evaluated. The extents of cranial resections were anterior cranial fossa in 20 cases, middle crania fossa in 16 cases and anterior and middle skull base in 10 cases. There were 18 patients undergoing orbital exenteration simultaneously. 14 cases had limitted dura resected because of dural involvement. RESULTS: The survival rate at 3 and 5 years was 48.8% (20/41) and 35.1% (13/37), respectively. The survival rate at 10 years was 20.0% (4/20). CONCLUSION: Our results revealed a considerably fine prospect of craniofacial resection for patients with advanced malignancies in oral and maxillofacial region. PMID- 11776921 TI - [Establishment and biological characteristics of vincristine: resistant cell line from human squamous cell carcinoma]. AB - OBJECTIVE: To establish a VCR-resistant cell line from human squamous cell carcinoma. METHODS: The cell line Tca8113 was utilized. The VCR concentration was increased gradually in consecutively passage of cultures. RESULTS: A VCR resistant cell line Tca8113/V100 from Tca8113 was established, the cells grew steadily in 100 mumol/L medium and with 19.2 times of resistance to VCR. The cell line was also resistant to ADM, PYM, CDDP, MTX, 5-Fu at different degrees. The doubling time of the cells was 37.2 hours and showed microscopically and ultrastructurally typical squamous cell carcinoma when inoculated in nude mice. Blot hybridization showed the cells had increased espression of MDR-1mRNA. CONCLUSION: These results indicate that the cell line has multidrug resistant ability, and the reason for this may be over expression of MDR-1 gene. This cell line provides an important model for the study on drug-resistant cell both in cellular and molecular level, and on the mechanism of drug resistance. PMID- 11776923 TI - [The application of color Doppler ultrasound technique in diagnosing the lumps of salivary gland]. AB - OBJECTIVE: To evaluate the value of color doppler ultrasound technique in diagnosing the lumps of salivary gland. METHODS: 233 cases of salivary gland lumps were examined with color doppler high frequency ultrusound technique. Among them were, 189 cases benign and the others malignant. RESULTS: Color doppler ultrasound technique could not only show the morphology, structure, sizc, location and adjoining relationship, but also indicate the pathological classification according to the blood supply. The total coincident rate of this ultrasound diagnosis to the pathological one was 89.3%. CONCLUSION: Color doppler ultrasound technique is a simple and harmless diagnosing method and could preoperatively give a reliable information to the decision of surgical plan. PMID- 11776922 TI - [CT evaluation of the primary extracranial neoplastic diseases eroding the central skull base]. AB - OBJECTIVE: To evaluate the central skull base erosion caused by primary extracranial mass lesions with CT. METHODS: Forty-nine patients (33 males and 16 females; mean, 40.2 years) suffered from the primary extracranial neoplastic diseases with middle skull base involvement were divided into two groups: group I (10 cases), primary osseous lesions of the central skull base and group II (39 cases), primary maxillofacial neoplasms. All lesions were confirmed histopathologically by surgery and biopsy. RESULTS: Four invasion patterns of the central skull base were identified on CT: I. resorption of the cortical bone (30 cases), including outer cortical margin destruction in 16 cases (group II lesions) and both inner and outer laminae resorption in 14 cases (4 group I lesions and 10 groups II lesions). II. ossification and thickening of the skull base (4 group I cases, all were fibrous dysplasia) III. erosive enlargement of the ovale and rotundam foramina (9 group II cases). IV. combined sclerosis and resorption of the skull base (6 cases, 2 group I lesions and 4 group II lesions). Involvement of the intracranial structures embraced the cavernous sinus (n = 12; group II lesions), temporal lobe (n = 11; 5 group I lesions and 6 group II lesions), and pituitary (n = 2, group II lesions). CT demonstrated the following central skull base structures were eroded: greater wing of sphenoid bone (n = 34), sphenoid body (n = 22), sphenoid process (n = 23), petrous bone (n = 15), and articular fossa of the temporal bone (n = 8). CONCLUSION: Osseous lesions originating from the central skull base have various CT manifestations. The cortical resorption of the central skull base may be regarded as a main pattern of bone erosion caused by primary maxillofacial neoplasms, and most of them have lesions involve the greater wing of sphenoid bone through the deeper maxillofacial spaces, such as the infratemporal, pterygopalatine and parapharyngeal spaces. PMID- 11776924 TI - [Effects of various condylar operations on its compressive mechanical property and bone density]. AB - OBJECTIVE: To investigate the changes and relationship of condylar mechanical properties and its material character after various condylar operations. METHODS: Condylar compressive mechanical properties and its bone mineral content were analyzed quantitatively by compressive mechanical property measurement technique and dual energy X-ray absorptiometry in 6 and 6 adult dogs undergone either high shaping or reconstruction of condyles respectively, and compared with 12 normals. RESULTS: Condylar elastic--limit load and displacement, its largest load and displacement were the highest in control, but stiffness and bone mineral content were the highest in high-shaping group, all data were the lowest in the reconstruction ones. There was marked and extremely marked linear positive relativity among condylar elastic--limit load, largest load, stiffness and bone density, in which all relative coefficients exceeded 0.862. CONCLUSION: The changes of condylar shape induced by various operations directly influence its compressive mechanical properties and bone mineral content. There is linear positive relativity between condylar compressive mechanical properties and its bone mineral density. PMID- 11776926 TI - [Evaluation of dental diseases and clinical therapy of children in 1990, 1995]. AB - OBJECTIVE: To study changes in patterns of children's dental diseases and their dental care improvements. METHODS: The survey was conducted on the basis of selection of 1,066 and 1,016 medical records of January, April, July and October of 1990 and 1995, respectively, from the complete hospital file. RESULTS: There was a distinct increase in pain and swelling as chief complaint, in regular check and in occlusal discrepancies, all with a significant difference of P < 0.01. No significant difference was found in caries and dental injury in both years. However in either of the two years caries remained the major dental disease. In dental treatment a significant difference (P < 0.01) indicated an increase in interception orthodontics and preventive treatment and a decrease in pulpal treatment. There was no remarkable differences in decay filling and extraction of teeth. CONCLUSION: The survey signified changes in patterns of children's dental diseases and evident improvement in children's dental therapy. PMID- 11776925 TI - [The effects of twin-block magnetic appliance on the early skeletal Class III malocclusion]. AB - OBJECTIVE: The aim of this study was to evaluate the effect of magnetic functional and orthopedic approach on treatment of early skeletal class III malocclusion. METHODS: A new type of magnetic twin-block appliance (TMA) was developed and used on 32 growing subjects with skeletal class III malocclusion. RESULTS: The class III dentofacial profile significantly improved and class III molar relationship was corrected in most cases. CONCLUSION: The Nd2-Fe14-B TMA could be used as effective orthopedic approach in treating class III malocclusion, which had many advantages, such as force prediction, well controlled anchorage, small and comfortable design of appliance and good cooperation from patients. PMID- 11776927 TI - [Clinical evaluation of gingival sulcus temperature in healthy subjects]. AB - OBJECTIVE: To evaluate gingival sulcus temperature in healthy subjects. METHODS: Small size, high sensitivity and rapid response thermocouple was used to measure the gingival sulcus temperature in seven dental students with healthy periodontium. 28 teeth in each subject were tested. RESULTS: For an individual subject, the gingival sulcus temperatures in all sites were always lower than sublingual temperature. There was obviously increased temperature gradient from anterior teeth to posterior teeth. The mean gingival sulcus temperatures on buccal sites were lower than that on lingual sites. There was no significant difference between maxillary and mandibular corresponding sites on lingual side. However, mandibular temperature was significantly lower than maxillary temperature on buccal side. Mandibular buccal temperature was the lowest in all tooth surfaces. CONCLUSION: Gingival sulcus temperature in subjects with healthy periodontium is easily influenced by environmental factors. PMID- 11776928 TI - [Vascularized illiac bone grafts and reconstruction of the mandible]. AB - OBJECTIVE: To investigate method of reconstructing large mandible defects. METHODS: Seven cases of mandibular defects were reconstructed with vascularied illiac bone grafts supplied by circumflex illiac vessels and Branemark osseointegration implants immediately. RESULTS: Six months after operation, X rays showed osseointegration between implants and graft bone. After 6 months to 36 months of follow-up, all implants were stable and no radiolucency was found and the functions were satisfactory in mastication, pronunciation and facial contour. CONCLUSION: Reconstruction of large mandible defects by vascularized illiac bone grafts supplied by circumflex illiac vessels and Branemark osseointegration implants immediately is promising. PMID- 11776929 TI - [Genetic analysis of tooth development and eruption in 82 pairs of female-female twins]. AB - OBJECTIVE: To study the heritability of tooth development and eruption. METHODS: 82 pairs of female-female twins between 6-12 years old were collected. Twin zygosity diagnosis were made by DNA-fingerprinting. The number of third molar present, hypodontia, upper lateral incisor malformation and the number of erupted permanent teeth were recorded by oral examination and panoramic radiographs, their heritabilities were calculated. RESULTS: According to the level of heritability, the dental traits were aligned as follows: the number of third molars present, the upper lateral incisor malformation, hypodontia and the number of erupted permanent teeth. CONCLUSION: Though both the tooth development and its eruption were under genetic influence, the heritability of tooth development was far more than tooth eruption. PMID- 11776930 TI - [Effects of endothelin-1 on the collagen synthesis of cultured human dental pulp cells]. AB - OBJECTIVE: To study the effects of endothelin-1(ET-1) on the collagen synthesis of cultured human dental pulp cells. METHODS: Cell cultured, enzyme linked immmun sorbent assay (ELISA), and ABC immunhistochemical staining were used in the study. RESULTS: ET-1 increased the synthesis of soluble type I collagen in different periods besides the 24 h group, and had no effects on the type III collagen; immunohistochemical staining revealed that ET-1 also increased the synthesis of unsoluble type I collagen. CONCLUSION: ET-1 can stimulate type I collagenic synthesis of human dental pulp cells and might have an effect on pulp self-restoration. PMID- 11776931 TI - [Collagen-binding proteins of human oral spirochetes]. AB - OBJECTIVE: To evaluate pathogenic effect of the collagen-binding proteins(CBP) of human oral spirochetes. METHODS: Immunoblot analysis, immunoelectron microscopy and other experiments had been used. RESULTS: It was showed that: type I, IV and V CBP were detected in heated and unheated preparations from Treponema denticola(Td) ATCC 33520 and Treponema socranskii (Ts) ATCC 35534. Few CBP, however, were detected in heated and unheated preparations from a recently characterized isloate, Treponema medium(Tm) strain G7201. 27,000 type V CBP of Td, 110,000 type I of Ts and 95,000 type IV of Tm were located on the envelopes of the individual cells. The adherence of Td to the collagen-coated surface was significantly greater than that of Tm. CONCLUSION: The CBP on the oral spirochetal cells play an important role in their adherence to collagen-rich connective tissues of the host. PMID- 11776932 TI - [Polylactic acid combined with recombinant human bone morphogenetic protein and basic fibroblast growth factor to repair the mandibular defects in rabbits]. AB - OBJECTIVE: To study the effect of basic fibroblast growth factor(bFGF) on bone formation induced by recombinant human bone morphogenetic protein-2(rhBMP-2) in repair of mandibular defects in rabbits. METHODS: 56 adult domestic rabbits were classified into five groups. The mandiblar three-wall defects(1.5 cm x 0.5 cm, full thick) were created in right sides. The defects were implanted with various grafts: PLA/rhBMP-2/bFGF, PLA/rhBMP-2, PLA/bFGF, PLA and no implant as control group. At 2, 4 and 8 weeks after operation, the effectivenesses of defect repaire were observed by histological and roentgenographic analysis. RESULTS: The composite consisting of three materials stimulated more bone formation than of two materials, and the latter was more than single PLA(at 4 weeks postoperation, P < 0.05). All experimental groups, which had one or two growth factors, were significantly higher compared with control group in every stage of postimplantation. CONCLUSION: PLA has good biocompatibility, absorbability and osteoconductibility, rhBMP-2 and bFGF are cooperated in bone healing process, and PLA/rhBMP-2/bFGF is a promising bone substitute in clinical uses. PMID- 11776933 TI - [Regulation of adherence to serum-coated hydroxyapatite by Streptococcus sanguis]. AB - OBJECTIVE: To investigate the effects of pH and calcium iron on adhesion of Streptococcus sanguis to serum-coated hydroxyapatite. METHODS: The adhesion model in vitro established by Clark W. B. in 1977 was used to quantify adsorptive cells through [3H] thymidine labelling. RESULTS: The cpm values between different pH groups showed significant differences. Also, there were significant differences of cpm values between calcium groups and control group. CONCLUSION: Either pH or calcium iron has obvious effect on adherence of Stroptococcus sanguis to serum coated hydroxyapatite. The findings suggest that regulating pH and concentration of calcium iron can help to change colonization on teeth surfaces by Streptococcus sanguis in periodontal circumstance. PMID- 11776934 TI - [Study on masticatory muscles and tooth long axis of miniature pigs]. AB - OBJECTIVE: The similarities of masticatory muscles and teeth orientations between miniature pigs and human beings were studied in order to evaluate the use of miniature pigs in oral biomechanics research. METHODS: By means of anatomy, the shapes, start-stop points and orientations of muscle of major masticatory muscles of miniature pigs were measured. Inclination of upper and lower teeth long axis was studied with lateral xray film of mandibles. RESULTS: The main masticatory muscles of miniature pigs include masseter muscle, temptory muscle, lateral pterygoid muscle, medial pterygoid muscle and zygomaticomandibular muscle. The angles of masticatory muscles and base plane are 63.9 degrees in massater muscle, 114.55 degrees in temple muscle, 64.4 degrees in medial pterygoidp muscle. The long axises of miniature pigs teeth are 6.1 degrees in the upper first molar, 6.5 degrees in the lower first molar, 7.3 degrees in the upper third premolar, 3.8 degrees in the lower third premolar. CONCLUSION: The masticatory muscles of miniature pigs are similar with human being in the shape, start-stop point and orientation of muscle force. The third premolar and the first molar of miniature pigs inclinate mesially, and are similar with the first premolar and the first molar of the human beings. Miniature pigs can be used as an animal models which can explain some problems of gnathostomatic system of human beings. PMID- 11776935 TI - [Comparative experimental study between longitudinal fracture and transverse fracture of mandibular condyle]. AB - OBJECTIVE: To evaluate the secondary effect of childhood miniature pig longitudinal fracture and transverse fracture of mandibular condyle to Temporomandibular Joint (TMJ). METHODS: Longitudinal and transverse fractures on condyle of 14 childhood miniature pigs were created respectively. After 3 and 6 months the TMJs were studied macroscopically and microscopically. RESULTS: The transverse fracture of mandibular condyle brought about TMJ adaptive changes. There was no adhesion between disc and condyle. The longitudinal fracture led usually to bifid condyle deformity and adhesion between disc and condyle. Many fibroblasts and chondrocytes were seen in the adhesion between disc and condyle. Blood vessels and fatty degeneration appeared in the articular disc. CONCLUSION: Two different types of childhood condylar fractures are apparently different in the aspects of secondary lesions on TMJ. It suggests that an evident correlation between mandibular condyle longitudinal fracture and TMJ ankylosis. PMID- 11776936 TI - [Changes of surface roughness and glossiness of the composite resins during polishing]. AB - OBJECTIVE: To investigate the changes of surface roughness and glossiness of the composite resins during polishing. METHODS: Nine conventional composite resins were evaluated. Composite specimens were polymerized on celluloid strip, so, smooth surfaces were obtained for each specimen, then the smooth surface of the specimens were sequentially polished with diamond polishing papers grits #240, #320, #400, #600, #800 and #1200. The roughness and glossiness of the central surface at 60 degrees reflex angle were measured. RESULTS: The results showed that the values of roughness decreased steadily when specimens were polished with sequential polishing paper from coarse to fine one. A further polishing with grit #800, the values of roughness resumed to the pre-polishing values in all the composite specimen. The change of values of glossiness is very small within polishing with #240-#600. A further polishing with grit #800 and #1200, the values of glossiness increased jumpily. The values of glossiness of five composite resins reached or surpassed the level of pre-polishing. CONCLUSION: This study indicates that fine surface would not be gained until the composite resins were polished with grit #800 and #1200 polishing paper. PMID- 11776937 TI - [The study on the personality factors in patients' satisfaction with their complete dentures]. AB - OBJECTIVE: To find out the relation between personality factors of edentulous patients and the degree of their satisfaction to the complete dentures. METHODS: Under the condition of controlling quality of complete dentures, 165 subjects were investigated by using the patient denture satisfaction questionnaire and the revised Cattell's 16 personality factors questionnaire after wearing the complete dentures for one and three months. RESULTS: The personality factors of edentulous patients such as conscientiousness (G factor), shrewdness (N factor) and so on do affect their denture satisfaction in every aspect of the dentures. CONCLUSION: The oral prosthodontists not only need improving technological quality of prostheses but also need paying attention to patients' psychological characteristics. PMID- 11776938 TI - Alopecia areata: topical immunotherapy--application and practical problems. PMID- 11776939 TI - Sixteenth annual meeting of the American Society for Hypertension, San Francisco, CA, USA, May 15-19, 2001. PMID- 11776940 TI - [A troublesome piriformis symptom]. PMID- 11776941 TI - Respecting life by "doing nothing". PMID- 11776942 TI - Risk of adverse birth outcomes near landfill sites. Evidence suggests that it is probably safe for fetuses to develop near landfill sites. PMID- 11776943 TI - Risk of adverse birth outcomes near landfill sites. Risks from landfill sites can be presented in alternative ways. PMID- 11776944 TI - Risk of adverse birth outcomes near landfill sites. News stories were handled badly. PMID- 11776945 TI - Risk of adverse birth outcomes near landfill sites. Local registers provide more accurate information. PMID- 11776946 TI - Diagnosing myocardial infarction. Randomised controlled trial and economic evaluation of a chest pain unit are in progress. PMID- 11776947 TI - Diagnosing myocardial infarction. Additional tools may help to identify patients at low risk. PMID- 11776948 TI - Patients and medical power. More debate about patient power in NHS is needed. PMID- 11776949 TI - Adaptive immune responses of patients with asthma to the attachment (G) glycoprotein of respiratory synctial virus. AB - A history of acute bronchiolitis in infancy caused by respiratory syncytial virus is a risk factor for recurrent wheezing in early childhood. Because the attachment (G) protein sensitizes mice for pulmonary eosinophilia and because Th2 cells are central in the pathogenesis of asthma, plasma and peripheral blood mononuclear cells (PBMC) from donors with asthma and from healthy donors were evaluated for anti-G protein responses. A significant trend connecting severity of asthma with anti-G protein IgG1 and IgG2 titers was observed. The correlation between anti-F protein IgG3 titers and asthma severity approached significance. Peptide mapping studies revealed that more positive recall responses (interferon gamma and interleukin-10 secretion) occurred after PBMC from donors with asthma were stimulated with peptides representing the nonglycosylated domain of G protein. The same peptides elicited more positive recall responses (proliferation and interferon-gamma secretion) in the PBMC of healthy donors. These data suggest that a mechanism may exist whereby adaptive immune responses against G protein contribute to wheezing. PMID- 11776950 TI - Clinical quiz: anaplastic large cell lymphoma. PMID- 11776951 TI - Pig and minipig cytochromes P450. PMID- 11776952 TI - The mouse uterotrophic assay: other end points. PMID- 11776954 TI - Are all cigarettes equal? PMID- 11776955 TI - Re: risk assessment of internal cancers from arsenic in drinking water. PMID- 11776956 TI - Rainfall runoff and the runs. PMID- 11776957 TI - Pollution 101. PMID- 11776958 TI - Old pesticides pose new problems for developing world. PMID- 11776959 TI - Bringing it all together. PMID- 11776960 TI - A day in the life of a VIP II coordinator. PMID- 11776961 TI - La Red: providing care to Delaware's disadvantaged. PMID- 11776962 TI - [Spontaneous rhythmic contractions of human placental vessels: is it an evidence for a physiological pacemaker in blood vessels?]. AB - BACKGROUND: Placental vessels are not innervated. Therefore the vasomotor activity and vascular tone is not regulated by the nervous system. AIM: To assess the existence of pacemaker mechanisms related to rhythmic motor activity of blood vessels. MATERIAL AND METHODS: Isometric contractions of rings from umbilical and chorionic vessels of term human placentas were monitored. RESULTS: Recordings of the circular layer of chorionic and umbilical vessels revealed rhythmic spontaneous contractions with a frequency of 1.4 +/- 0.05 cycles/min, the duration of each cycle was 42.8 +/- 0.24 s (n = 12). The amplitude of contractions was larger in veins than in arteries, predominating in umbilical vein biopsies, proximal to the fetus. Both the frequency and the amplitude of contractions were relatively constant during the first 30 min. However, after an hour, the frequency declined while the amplitude increased. The absence of the endothelium neither modified the frequency nor the amplitude of the rhythmic activity. Blockage of voltage dependent sodium channels or calcium channels did not alter the frequency of spontaneous contractions, although their magnitude was reduced. Glibenclamide, an ATP-dependent K+ channel blocker or the blockade of gap junctions ablated the frequency and amplitude of spontaneous contractions. CONCLUSIONS: We propose that rhythmic contractions are triggered by pacemaker cells located in the circular layer of the smooth muscle of blood vessels and spread via gap junctions; they likely contribute to the control of blood flow. PMID- 11776963 TI - Establishment and characterization of nine human brain tumor cell lines. PMID- 11776964 TI - Synthesis of extracellular matrix proteins in bovine mammary epithelial cells. PMID- 11776965 TI - Reference recombinant chinese hamster ovary cell lines. PMID- 11776966 TI - Factors in serum regulate Nkx2.5 and MEF2C function. PMID- 11776967 TI - An ENF peptide, Bombyx mori paralytic peptide, induces cell proliferation and morphological changes in Bombyx cell lines. PMID- 11776968 TI - Expression of surface CD40 and immunocytochemical actin-bundling protein fascin in dendritic cells from multiple myeloma treated with retinoids during their differentiation in vitro. PMID- 11776969 TI - The culture of fibroblasts from diaphragm of giant panda. PMID- 11776970 TI - Innocuousness and intracellular distribution of PKH67: a fluorescent probe for cell proliferation assessment. AB - PKH dyes were initially developed by Horan et al. to provide appropriate probes for in vitro and in vivo cell tracking. It has been reported for many cell types that PKH bind irreversibly to the cell membrane without significantly affecting cell growth. Thus, these probes provide an opportunity for long-term cell monitoring and the identification of cells of interest among a heterogeneous cell population. An important feature is that upon cell division, the probe is partitioned equally between each daughter cell, making it possible to quantify tell fluorescence by flow cytometry. In this situation. the flow cytometric study of PKH67 characteristics shows that this probe does not affect the main cell functions such as viability or proliferation. Moreover, the intracellular distribution of PKH67 is demonstrated by following its kinetics of internalization by confocal microscopy. These results present PKH67 as a probe suitable for dynamic analysis of cell proliferation as well as the study of intracellular localization and membrane recycling mechanisms. PMID- 11776971 TI - Effects of medium composition on the morphology and function of rat hepatocytes cultured as spheroids and monolayers. AB - Primary hepatocytes cultured as monolayers or as spheroids were studied to compare the effects of four different culture media (Williams' E, Chee's, Sigma Hepatocyte, and HepatoZYME medium). Rat hepatocytes were cultured as conventional monolayers for 3 d or as spheroids for 2 wk. For spheroid formation a method was emplOyed that combined the use of a nonadherent substratum with rotation of cultures. Hepatocyte integrity and morphology were assessed by light and electron microscopy and by reduced glutathione content. Hepatocyte function was measured by albumin secretion and 7-ethoxycoumarin metabolism. Chee's medium was found to be optimal for maintenance of hepatocyte viability and function in monolayers, but it failed to support spheroid formation. For spheroid formation and for the maintenance of spheroid morphology and function, Sigma HM was found to be optimal. These results demonstrate that the medium requirements of hepatocytes differ markedly depending on the culture model employed. Spheroid culture allowed better preservation of morphology and function of hepatocytes compared with conventional monolayer culture. Hepatocytes in spheroids formed bile canaliculi. and expressed an actin distribution resembling that found in hepatocytes in vivo. Albumin secretion was maintained at the same level as that found during the first d in primary culture, and 7-ethoxycoumarin metabolism was maintained over 2 wk in culture at approximately 30% of the levels found in freshly isolated hepatocytes. The improved morphology and function of hepatocyte cultures as spheroids may provide a more appropriate in vitro model for certain applications where the maintenance of liver-specific functions in long-term culture is crucial. PMID- 11776972 TI - Methemoglobin is a supplement for in vitro culture of human nasopharyngeal epithelial cells transformed by human papillomavirus type 16 DNA. AB - NPC-N cells were normal human nasopharvngeal epithelial cells transformed by transfection with human papillomavirus type 16 deoxyribonucleic acid. Bovine pituitary extract (BPE) was one of the indispensable ingredients for in vitro culture of NPC-N cells in a serum-free medium. Chromatographic fractionation of BPE and subsequent immunoblotting analyses identified the hemoglobin growth stimulating factor. Methemoglobin (metHb) was then synthesized, and also found to be growth stimulating. The growth-stimulating effect of metHb was abolished when NPC-N cells were cultured in a medium that also contained haptoglobin, a molecule that binds to hemoglobin. A defined medium consisting of insulin and metHb was then developed for optimal growth of NPC-N cells. MetHb kept under the conditions identical to those of cell culture released hemin which also enhanced the cell growth. Though all the degradation products of hemin are currently known to be physiologically significant. only ferric iron derived from metHb or hemin could stimulate the growth of NPC-N cells. Abnormal vasculature showing leaky walls and hemorrhage is a common feature of malignant tumors. Hemoglobin originating from extravasated red blood cells and subsequently oxidized to metHb because of the presence of activated inflammatory cells might contribute to the increased proliferation of cancerous cells. PMID- 11776973 TI - Feline head and neck squamous cell carcinoma cell line: characterization, production of parathyroid hormone-related protein, and regulation by transforming growth factor-beta. AB - A natural animal model for human head and neck squamous cell carcinoma (H/N SCC) has not been described. The domestic cat has a high spontaneous occurrence of oropharyngeal SCC, which is similar to the human disease in aggressiveness and incurability. We have developed a cell line (SCCF1) from a laryngeal SCC of a cat. Keratinocytes were maintained in culture for greater than 50 passages. SCCF1 had strong cytokeratin immunohistochemical staining, weak vimentin staining, and no p53 staining. Ultrastructual features included cytokeratin filaments and desmosomes, as well as features of anaplasia (irregular cytoplasmic and nuclear margins, surface filopodia, and abnormal intermediate filament production). Karyotype analysis revealed aneuploidy, with a stemline chromosomal number of 34. The cells grew logarithmically for 6 d until confluency. SCCF1 expressed parathyroid hormone-related protein (PTHrP) messenger ribonucleic acid (mRNA) and protein, and secreted the protein into the medium. Treatment of SCCF1 with transforming growth factor-beta increased PTHrP production but did not affect PTHrP mRNA stability. Reverse transcriptase-polymerase chain reaction was used to amplify a 282-base pair region of feline PTHrP mRNA, encoding portions of the pre pro and coding regions. The complementary deoxyribonucleic acid (cDNA) was cloned and sequenced. The cDNA and the predicted amino acid sequences had a high degree of homology to human and canine PTHrP. RT-PCR was used to confirm alternate splicing of PTHrP mRNA for translation of PTHrP 1-139 and PTHrP 1-141. The SCCF1 cell line will permit mechanistic experiments on genetic dysregulation in neoplastic keratinocytes of the feline oropharynx, and development of an in vitro model for H/N cancer. PMID- 11776974 TI - Transcriptional regulation of the transforming growth factor-beta2 gene in glioblastoma cells. AB - The expression of transforming growth factor-beta2 (TGF-beta2) appears to play a strong role in the establishment and progression of glial tumors. In particular, elevated expression of TGF-beta2 appears to be responsible for the impaired cell mediated immunity often observed in patients with a glioblastoma. This study examined the regulation of the TGF-beta2 at the transcriptional level in the U87MG glioblastoma cell line. We demonstrate that a cAMP response element/activating transcription factor (CRE/ATF) site and an E-box motif located just upstream of the transcription start site are essential for the transcription of the TGF-beta2 gene in U87MG cells. Gel mobility analysis determined that activating transcription factor-1, and possibly cAMP-responsive element binding protein, binds to the CRE/ATF site, and upsteam stimulatory factor (USF) 1 and USF2 bind to the E-box motif. Interestingly, expression of a dominant negative USF protein down-regulates TGF-beta2 activity by 80-95% in glioblastoma cells. We conclude that the binding of transcription factors, in particular the USF proteins, to the TGF-beta2 promoter is essential for its expression and possibly its up-regulation in glioblastomas. PMID- 11776975 TI - Phosphatidylethanolamine deficiency in membrane lipids inhibits keratinocyte intercellular networks formation. AB - Ethanolamine (Etn) is required for the growth of epithelial cells in culture. Without Etn, the amount of phosphatidylethanolamine (PE) in membrane lipids is reduced, and cell proliferation stops. When the membrane lipids are deficient of PE, some extracellular signaling processes become impaired. In this study, we examined the effect of Etn deprivation on the formation of intercellular networks in immortalized human oral keratinocytes. Keratinocytes proliferate with undifferentiated morphologies in a low-calcium medium, whereas they undergo differentiation to form intercellular networks in a high-calcium medium. The cells were first cultured with or without Etn supplement in a low-calcium (0.07 mM) medium, and then the calcium concentration was raised to 1.8 mM. The localization and organization of the following proteins were examined: (1) desmogleins and plakoglobin in desmosomes, (2) E-cadherin and beta-catenin in adherens junctions and (3) actin and keratin filaments in cytoskeletons. As expected, in the Etn-supplemented cells, the elevated level of calcium induced the junctional localization of the proteins associated with desmosomes and adherens junctions and also induced the formation of keratin and actin networks. On the contrary, in the Etn-deprived cells, the elevated level of calcium induced none of the above processes. The results suggest that having a sufficient amount of PE or proper phospholipid composition in the membranes is crucial for differentiation in epithelial cells. PMID- 11776977 TI - [Augustin Belloste (1654-1730), from military surgery to mercurial therapeutics]. PMID- 11776976 TI - Oncostatin m regulates mesenchymal cell differentiation and enhances hematopoietic supportive activity of bone marrow stromal cell lines. AB - Bone marrow stromal cell lines (TBR cell lines) established from temperature sensitive Simian Virus 40 T-antigen gene transgenic mice exhibited myogenic, osteogenic, and adipogenic differentiation. The effect of oncostatin M (OSM) on such mesenchymal cell differentiation of marrow stromal cell lines was examined. One of those stromal cell lines, TBRB, differentiated into skeletal muscle, and its differentiation was stimulated by OSM, whereas differentiation of TBR10-1 into smooth muscle was inhibited by OSM. TBR31-2 is a bipotent progenitor for adipocytes and osteoblasts, and OSM stimulated osteogenic differentiation while inhibiting adipogenic differentiation. On the other hand, TBR cell lines exhibited various potentials for supporting hematopoiesis in culture. When hematopoietic progenitor cells were cocultured with OSM-stimulated stromal cell lines, TBR10-1 and TBR31-2 exhibited enhanced hematopoietic supportive activity. As responsible molecules for stromal cell dependent hematopoiesis, expression of stem cell factor (SCF) (a ligand of c-Kit), vascular cell adhesion molecule (VCAM 1) (a ligand of VLA-4), and secretion of interleukin (IL)-6 were increased by OSM. OSM affected mesenchymal cell differentiation and promoted the hematopoietic supportive activity of marrow stromal cell lines. As OSM production is induced by cytokines from hematopoietic cells, OSM may be a key factor in mutual regulation between hematopoietic cells and stromal cells in the bone marrow. OSM may play a role as a regulator in maintaining the hematopoietic microenvironment in marrow by coordinating mesenchymal differentiation. PMID- 11776978 TI - [Filmstrips and public health]. AB - In this article, the author presents an abandoned audiovisual technique: the "filmstrip". He is interested in connections between this technique and the health service, and more particularly in filmstrips produced by the "Securite sociale" in France. PMID- 11776979 TI - [The old Issoudun's hospital pharmacy]. AB - After presentation of the history, functioning and administration of the pharmacy, the authors take an interest in the rich pharmaceutical things collection : pots in Nevers' earthenware of XVIIth and XVIIIth centuries, wooden boxes of herbals to XVIIth century, Venice's glass receptacles of the Renaissance, mortars and still, books, furniture. PMID- 11776980 TI - DNA fragmentation induced in K562 cells by nitrogen ions. AB - This study was aimed at investigating the radiation induced DNA fragmentation pattern as a function of cellular differentiation and radiation quality. DNA double strand breaks (DSB) induced by gamma-rays were analyzed in K562 human proerythroblasts before (AP cells) and after (D cells) differentiation induction while DNA DSB induced by 125 keV/micrometers N-ions have been studied in AP cells. Pulsed-Field Gel Electrophoresis (PFGE) of cellular DNA was used to determine the DSB yield by analysis of the Fraction of Activity Released (FAR) and of the fragmentation pattern in a specific size range (5.7-0.225 Mbp). The results so far obtained show that the DSB induction by gamma-rays is different if evaluated with the FAR or with the fragmentation analysis. The DSB yield obtained with the former method is about 1.4 times higher in AP respect to D cells while the latter method indicates that more fragments are produced in D cells. Comparison between gamma-rays and N-ions in AP cells shows that no significant differences are detected by the FAR analysis; otherwise fragmentation analysis demonstrates a higher effectiveness of nitrogen ions. PMID- 11776981 TI - The effect of space radiation on the induction of chromosome damage. AB - To obtain information on the cytogenetic damage caused by space radiation, chromosome exchanges in lymphocytes from crewmembers of long-term Mir missions, and a shorter duration shuttle mission, were examined using fluorescence in situ hybridization. A significant increase in chromosomal aberrations was observed after the long duration flights. The ratio of aberrations identified as complex was higher post-flight for some crewmembers, which is thought to be an indication of exposure to high-LET radiation. Ground-based studies have shown that the frequency of aberrations measured post-flight could be influenced by a mitotic delay in cells damaged by high-LET radiation and this effect could lower biological dose estimates. To counteract this effect, prematurely condensed chromosome (PCC) spreads were collected. Frequencies of aberrations in PCC were compared with those in metaphase spreads. PMID- 11776982 TI - Kinetics of chromatid break repair in G2-human fibroblasts exposed to low- and high-LET radiations. AB - The purpose of this study is to determine the kinetics of chromatid break rejoining following exposure to radiations of different quality. Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290 MeV/u), silicon (490 MeV/u) and iron (200 MeV/u, 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Prematurely condensed chromosomes were collected after several post-irradiation incubation times, ranging from 5 to 600 minutes, and the number of chromatid breaks and exchanges in G2 cells were scored. The relative biological effectiveness (RBE) for initial chromatid breaks per unit dose showed LET dependency having a peak at 55 keV/micrometers silicon (2.4) or 80 keV/micrometers carbon particles (2.4) and then decreased with increasing LET. The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components. Chromatid breaks decreased rapidly after exposure, and then continued to decrease at a slower rate. The rejoining kinetics was similar for exposure to each type of radiation, although the rate of unrejoined breaks was higher for high-LET radiation. Chromatid exchanges were also formed quickly. PMID- 11776983 TI - Comparison of chromosome aberration frequencies in pre- and post-flight astronaut lymphocytes irradiated in vitro with gamma rays. AB - If radiosensitivity is altered in a microgravity environment, it will affect the accuracy of assessing astronauts' risk from exposure to space radiation. To investigate the effects of space flight on radiosensitivity, we exposed a crewmember's blood to gamma rays at doses ranging from 0 to 3 Gy and analyzed chromosome aberrations in mitotic lymphocytes. The blood samples were collected 10 days prior to an 8-day Shuttle mission, the day the flight returned, and 14 days after the flight. After exposure, lymphocytes were stimulated to grow in media containing phytohaemagglutinin (PHA) and mitotic cells were harvested for chromosome analysis using a fluorescence in situ hybridization (FISH) with whole chromosome specific probes. The dose response of total exchanges showed no changes in the radiosensitivity after the mission. PMID- 11776984 TI - Standardization of the comet assay technique on FRTL5 cells. AB - The comet assay is a sensitive and rapid method for DNA strand break detection in individual cells. The principle of break detection, using either the alkaline or neutral version of the assay, makes it a good technique for studying both double and single strand DNA breaks. Furthermore, the possibility of following DNA damage at different time moments also makes it possible to investigate the cell repair mechanisms. This explains why in the last few years there has been a tremendous increase in the number of laboratories which started to use this technique. The technique was first created for lymphocyte cells and later on has been used on many other cell types, growing both in suspension and adherent. To date, no one has applied this technique on normal differentiated endocrine cells, such as FRTL5 cells (Fisher Rat Thyroid Cells). The aim of this study has been to standardize the alkaline version of the Comet Assay technique on FRTL5 cells by studying the kinetics of DNA-damage and DNA-repair after different doses of UV-C (254 nm). FRTL-5 cells not only resulted very sensitive to UV-C (p<0.05 at 5 J/m2), but were also able to repair most of their DNA damage very rapidly (within one hour) as shown by a significant exponential regression in comet length. Finally, the successful measurement of biomarkers of UV-C on thyroid cells established the comet assay as a valuable tool in measurement of DNA damage and repair. Any radiation, or other damaging agents, interacting with living organisms could cause DNA damages which, depending upon dosages and kinetics of exposure, may or may not be completely repaired. PMID- 11776985 TI - Mechanisms of mutagenesis in human cells exposed to 55 MeV protons. AB - Protons represent the major type of charged particle radiation in spaceflight environments. The purpose of this study was to assess mutations arising in human lymphoid cells exposed to protons. Mutations were quantitated at the thymidine kinase (TK1) locus in cell lines derived from the same donor: TK6 cells (wt TP53) and WTK1 cells (mutant TP53). WTK1 cells were much more susceptible to mutagenesis following proton exposure than TK6 cells. Intragenic deletions were observed among early-arising TK1 mutants in TK6 cells, but not in WTK1 cells where all of the mutants arose by LOH. Deletion was the predominant mode of LOH in TK6 cells, while allelic recombination was the major mode of LOH in WTK1 cells. Deletions were of variable lengths, from <1 cM to 64 cM, while mutations that arose by allelic recombination often extended to the telomere. In summary, proton exposures elicited many types of mutations at an autosomal locus in human cells. Most involved large scale loss of genetic information, either through deletion or by recombination. PMID- 11776986 TI - Genomic instability in human lymphoid cells exposed to 1 GeV/amu Fe ions. AB - The goal of this study was to assess whether charged particle radiations of importance to spaceflight elicit genomic instability in human TK6 lymphoblasts. The incidence of genomic instability in TK6 cells was assessed ~21 days after exposure to 2, 4, or 6 Fe ions (1 GeV/amu, LET= 146 keV/micrometers). Three indices of instability were used: intraclonal karyotypic heterogeneity, mutation rate analysis at the thymidine kinase (TK1) locus, and re-cloning efficiency. Fifteen of sixty clones demonstrated karyotypic heterogeneity. Five clones had multiple indicators of karyotypic change. One clone was markedly hypomutable and polyploid. Six clones were hypomutable, while 21 clones were mutators. Of these, seven were karyotypically unstable. Six clones had low re-cloning efficiencies, one of which was a mutator. All had normal karyotypes. In summary, many clones that survived exposure to a low fluence of Fe ions manifested one or more forms of genomic instability that may hasten the development of neoplasia through deletion or by recombination. PMID- 11776987 TI - Effect of space radiation on expression of apoptosis-related genes in endometrial cells: a preliminary study. AB - In this paper we present some preliminary results on alteration of gene expression caused by radiation on human endometrial cells. To this purpose, we have studied the modulation of the expression of the bcl-2 gene family in two cell lines following irradiations with low energy protons and gamma-rays from a 60Co. The two epithelial cell strains, namely AN3Ca and HEC1B cells, both obtained from human neoplastic endometrial tissues, grow in culture and continue to maintain some differentiated functions typical of the original tissue. Indeed, these cells, that can be considered as representative of different stages of cellular transformation of endometrium. Because their epithelial nature and rapid growth, the expression of genes related to the maintenance of the cellular homeostasis (correction of omeostasis), as the pro and anti-apoptotic ones, is expected to be susceptible to changes in environment, including radiation. The effects have been evaluated in terms of both cell survival and changes in the expression of pro- and anti apoptotic proteins. Even though the data reported above can not be considered complete and/or definitive, nevertheless, in whole, they confirm that these cells may constitute a suitable model system to study, at molecular level, the effects of cosmic radiation on endometrium. Further observation, ensuing from these preliminary data, is that endometrial cells present different sensitivity to radiation in regard to its 'quality' and 'dosage', in accord to the original stage of differentiation. PMID- 11776988 TI - Modulation of lens cell adhesion molecules by particle beams. AB - Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast, there was a dose-dependent increase in ICAM-1 immunofluorescence in confluent, but not exponentially-growing cells. These results suggest that proton irradiation downregulates beta 1 integrin and upregulates ICAM-1, potentially contributing to cell death or to aberrant differentiation via modulation of anchorage and/or signal transduction functions. Quantification of the expression levels of the CAMs by Western analysis is in progress. PMID- 11776989 TI - Radiation shielding of astronauts in interplanetary flights: the CREAM surveyor to Mars and the magnetic lens system for a spaceship. AB - The radiation absorbed by astronauts during interplanetary flights is mainly due to cosmic rays of solar origin (SCR). In the most powerful solar flares the dose absorbed in few hours can exceed that cumulated in one year of exposition to the galactic component of cosmic rays (GCR). At energies above the minimum one needed to cross the walls of the spaceship there are extrapolations and guesses, but no data, on the angular distribution of SCR's, an information that is necessary for establishing whatever defence strategy. It was therefore proposed of sending to Mars a measurement device, that should continuously collect data during the travel, and possibly also in the orbit around Mars and on the Mars surface. The device should identify the particle and privilege the completeness in the measurement of its parameters. In fact the high energy electrons travel at speed of the light and could be used in the and future dangerous proton component. Also the much less abundant but individually more dangerous ions should be identified. The device should indeed include a magnetic spectrometer and a high granularity range telescope, and a good time of flight measurement. ASI is supporting an assessment study of a possible mission of such a device on board of the 2005 probe to Mars. A parallel technical study is also in progress to define the workable techniques and the possible configurations of a system of magnetic lenses for protecting the crew of a spaceship. PMID- 11776990 TI - The ALTEA facility on the International Space Station. AB - The ALTEA project studies the problems related to possible functional damage to the Central Nervous System (CNS) due to particle radiation in space environment. The project is a large international and multi-disciplinary collaboration. The ALTEA instrumentation is an helmet-shaped multi-sensor device that will measure concurrently the dynamics of the functional status of the visual system and the passage of each particle through the brain within a pre-determined energy window. ALTEA is scheduled to fly in the International Space Station in February 2003. One part of the multi-sensor device, one of the advanced silicon telescopes, will be launched in the ISS in early 2002 and serve as test for the final device and as discriminating dosimeter for the particle fluences within the ISS. PMID- 11776991 TI - [Beginnings of the study of Western sciences, "Rangaku," in Kyoto and Osaka in close relations with the Edo school]. AB - Beginnings of the study of Western sciences, "Rangaku," in Kyoto and Osaka in the late 18th century are reviewed. Profiles and achievements of several active learners are briefly described; they include Koishi Genzui (Osaka-Kyoto), Tsuji Ranshitsu (Kyoto), Kimura Kenkado (Osaka), and Hashimoto Sokichi (Osaka). Genzui, after having successfully made good relations with Sugita Genpaku and Ohtsuki Gentaku, leading masters of the Edo school, played a role of an advocator for promoting "Rangaku" in Osaka and Kyoto. As a result, Kenkado attained the publication of his book "Ikkaku Sanko," a monograph of the Western crude drug unicorn, with the help of Gentaku, who had translated a Dutch reference into Japanese for him. Ranshitsu and Sokichi were taught the Dutch language by Gentaku; Sokichi is known as the founder of "Rangaku" in Osaka. PMID- 11776992 TI - [Wood creosote: a historical study and its preparation in combination with herbal drugs]. AB - Two kinds of creosote have been found based on historical evidence of the medicinal uses and origins. One is wood creosote, and distillate of wood-tar containing guaiacol and creosol. The other type of creosote is coal-tar creosote, obtained from coal-tar, containing naphthalene and anthracene as the major constituents. Wood creosote was prepared for the first time in Germany in 1830 and was used for medicinal purposes. It had been listed officially in the German, American, and Japanese Pharmacopoeia as an antibacterial agent for the treatment of pulmonary tuberculosis, diarrhea, and external injury. In recent days, it has been deleted from the Pharmacopoeia in Western countries and not officially used for medicinal purposes. However, wood creosote is still been listed in the Japanese Pharmacopoeia and is used for the treatment of diarrhea. Since the interest of common people in herbal medicines and self-medication has been increasing, the use of wood creosote has also been modified in combination with some herbal drugs, "Seiro-gan" especially is quite popular in Japan as a self medication for digestive trouble, including food poisoning or diarrhea. PMID- 11776993 TI - [Metallurgic drugs in ancient Japan]. AB - Advancements in metallurgic and pharmaceutical chemistry in ancient Japan were made by people like Mangan-Shonin, who combined elements from Shinto, Buddhism, and Taoism to take advantage of technologies brought by Chinese and Korean immigrants. The Shonin himself, though it may be considered a wild speculation, could well be such an immigrant. Along with the immigrants, the Shonin established government-subsidized temples (Jingu-ji, Jogaku-ji) throughout the country under sponsorship by the Imperial Court for the purpose of raising funds through private donations. Research and educational activities conducted in these temples ultimately resulted in a well-established body of chemical engineers who could excavate chemical substances as well as alter their natures. According to a list of regional products (Sasaki,19) 1972) up to the 14th century, these chemical substances and their derivative products included iron from the Hitachi region, cast metal from Shimotsuke, swords from Sagami, face powder (lead carbonate) from Ise, mercury, and gold. PMID- 11776994 TI - [Camphor in the Edo era fireworks]. AB - Guns and gunpowder were introduced into Japan in 1543 by the Portuguese, and they soon began to be made in Japan by the Japanese. The powder was used also for making fireworks. The brilliance of fireworks was darker and the scale was less in the Edo period. Various materials were added to the powder to make the fireworks more brilliant. Camphor was one of them, though the volume was slight and the frequency of adding it was small. Camphor had been used for torch-light materials before the Edo period, so it seems logical that it would be added to powder for fireworks. PMID- 11776995 TI - [Discovery of the adult Schistosoma japonicum, a causative agent of Schistosomiasis in the Katayama area of Hiroshima Prefecture]. AB - People in the Katayama area of Hiroshima Prefecture had been afraid of a curious disease for a long time. The causative agent for the disease had not been identified through the beginning of the 20th century when it turned out that a human parasitic trematode, Schistosoma japonicum, had been afflicting the inhabitants, causing this disease. This was made clear mainly by two medical doctors, Akira Fujinami and Ryuzo Yoshida, much before 1909. The memoir on the disease described by a herb doctor, Yoshinao Fujii (1847), was made known by A. Fujinami to medical scientists in 1909. PMID- 11776996 TI - [Transition of Japanese societies related to clinical chemistry in the Mid-Showa period (1955-1980) (Part 2)]. AB - The transitions of research activities in the field of clinical chemistry in the Japan Society for Analytical Chemistry, in the Japan Pharmaceutical Association, and the other three related research groups since 1966 were briefly reviewed. PMID- 11776997 TI - [The coriander story]. AB - The etymology of coriander starts with the Greek koriannon, a combination of koris (a stinking bug) and annon (a fragrant anise). In Latin, it was spelled coriandrum, and by way of Old French it came into English as coriander in the 14th century. A historical account of Coriandrum sativum mainly Japan is presented. It had been known as a foodstuff in the 10th century, but it disappeared in the next century perhaps because of its disagreeable smell. It was reintroduced by the Portuguese in the 18th century as ko-en-do-ro in Japanese, from the Portuguses word coentro. The smell of the fresh leaves should be a product of a mixture of essential oils including d-linalol or coriandrol. PMID- 11776998 TI - [Etymology of ginger]. AB - The English term ginger originates from Sanskrit sringavera (sringam=horn+vera=body), which was transformed to Latin gingiber and to Old French gingibre, which resulted in ginger in English. The German Ingwer was derived from the same origin, but lost its front sound. The Chinese and Japanese terms for ginger are briefly discussed. And the etymology of the related words gingerbread and ginger ale are also mentioned. PMID- 11776999 TI - [Social significance of pharmaceutical education]. PMID- 11777000 TI - [Forgotten episodes of the birth of cortisone]. AB - During World War II, a rumor reached the United States and the United Kingdom that the Germans were successfully using an adrenal hormone product to protect Luftwaffe pilots from the adverse effects of high altitudes. The product was said to be obtained from adrenal glands collected in a huge amount in Argentina and transported by U-boats to Germany. The U. S. and the U. K. exerted their war efforts by setting up urgent research projects to produce similar products. The war ended in 1945, however, before the goal was achieved. The German rumor turned out to be groundless. Cortisone acquired fame in 1949 as "a miracle drug" for the relief of rheumatic pain. Its therapeutic discovery was an outcome of the untenable assumption that rheumatoid arthritis patients must have suffered from adrenal insufficiency and hormone deficiency. The war efforts have led to successful syntheses of cortisone after the war, and its industrial production has reduced its cost drastically from $200.00 per gram in 1949 to $10.00 in 1951. To overcome the cumbersome synthetic routes for cortisone, natural product sources were sought as possible starting materials, but without much success. A microbiological transformation of steroidal compounds was developed in 1952 to introduce an oxygen function into the molecular position 11 by a microorganism found at a window of a laboratory. The fermentation process required progesterone which found its timely supply in Mexico. The cost of progesterone went down from $2.00 per gram to $0.15 and that of cortisone further from $10.00 to $3.50 in 1955. An ample supply of cortisone at an affordable price was admirably achieved by the combination of progesterone derived from diosgenin of the Mexican yam and a microbiological oxidation process developed by a chance discovery of suitable organisms. The former is attributed to R. E. Marker and the latter to D. H. Peterson. PMID- 11777001 TI - [The nutmeg story]. AB - A brief historical account of the spice islands, the Moluccas, in the Age of Discovery with particular reference to the Dutch monopoly of nutmeg is presented. The etymologies of such English terms as nutmeg (nut+musk), mace, myristica, date, and phoenix, as well as Chinese rou dou kou (Engl. nutmeg) and Japanese natsume (Engl. jujube) and natsume-yashi (Engl. date palm) are given. PMID- 11777002 TI - [Kinoshita's natural colored book of medicinal plants]. AB - This book is well preserved in the Ashimori Kaikan (an exhibit of Okayama city). This paper describes the book of medicinal plants in detail. PMID- 11777003 TI - RseB binding to the periplasmic domain of RseA modulates the RseA:sigmaE interaction in the cytoplasm and the availability of sigmaE.RNA polymerase. AB - The Escherichia coli sigmaE regulon has evolved to sense the presence of misfolded proteins in the bacterial envelope. Expression of periplasmic chaperones and folding catalysts is under the control of sigmaE RNA polymerase. The N-terminal domain of RseA sequesters sigmaE in the cytoplasmic membrane, preventing its association with core RNA polymerase. The C-terminal domain of RseA interacts with RseB, a periplasmic protein. The relative concentration of sigmaE:RseA:RseB is 2:5:1 and this ratio remains unaltered upon heat shock induction of the sigmaE regulon. Purification from crude cellular extracts yields cytoplasmic, soluble sigmaE RNA polymerase as well as membrane sequestered sigmaE.RseA and sigmaE.RseA.RseB. RseB binding to the C-terminal domain of RseA increases the affinity of RseA for sigmaE by 2- to 3-fold (Kd 50-100 nM). RseB binds also to the misfolded aggregates of MalE31, a variant of maltose binding protein that forms inclusion bodies in the periplasm. We discuss a model whereby the RseB-RiseA interaction represents a measure for misfolded polypeptides in the bacterial envelope, modulating the assembly of sigmaE RNA polymerase and the cellular heat shock response. PMID- 11777004 TI - Oestrus ovis in sheep: relative third-instar populations, risks of infection and parasitic control. AB - Oestrus ovis (L.) (Diptera: Oestridae), the nasal bot fly, has a relatively short free-living life cycle outside of the host, and therefore it is necessary to know when the parasitic period occurs in order to prevent the clinical signs and economic losses caused by this parasite. The length of this parasitic portion of the life cycle is quite variable: a few weeks to several months depending on the season and climatic conditions. Surveys of Oestrus ovis larval populations in sheep show different results on the number of generations according to the local climate. Mean monthly larval profiles of L1 and L3 burdens of sheep from West African Sahelian countries, Mediterranean countries (Morocco, Tunisia and Sicily) and Southwest France were compared. Valuable information on the suspected extension of the fly season is obtained showing the period of infection in each area. This knowledge will be a valuable tool to help in choosing the right treatment at the right period. PMID- 11777005 TI - The crucial question of standardisation when measuring drug consumption. AB - The reliability of drug consumption studies will depend on agreement on an international unit of measurement and the provision of accurate descriptions of patterns of use. This measurement unit should permit comparisons between countries and periods of time. Different units have been proposed and published. Consumption may be expressed in terms of pharmaceutical firm turnover, therapeutic costs, weight (total weight or dose equivalent), treatment doses such as defined daily dose and prescribed daily dose, or as number of items or packages sold. The advantages and disadvantages of the different evaluation units used in veterinary medicine are reviewed. PMID- 11777006 TI - Proposed criteria to determine whether a territory is free of a given animal disease. AB - This text describes the general principles underlying the concept of disease-free territory and the required statistical basis for the corresponding epidemiological surveillance operations. Among the essential points, it is emphasised that "disease-free" status should be given only under conditions substantiating the absence of infection (or infestation) and not simply on basis of a known low level of infection (or infestation). This manuscript also raises concerns about possible confusion that has arisen between the inevitable requirement to set a threshold on the level of detection of epidemiological surveillance tools, for economic reasons, and the acceptance of a level of infection (or infestation) that is known, but occurring below the accepted threshold, when according the official status of "territory-free from a given disease". In such a situation, it would be preferable to accord the status of "territory where the disease is in the process of eradication". PMID- 11777007 TI - Effect of milk sampling techniques on milk composition, bacterial contamination, viability and functions of resident cells in milk. AB - Three different milk sampling techniques were evaluated during milk sampling: a direct aseptic collection from the udder through a sterile cannula was used as the reference technique, compared with either a manual or a mechanical sampling method. In this study 30 high-yielding Holstein-Friesian dairy cows at different stages of lactation and free of udder infection were used. For each milk sample, the influence of milk sampling techniques was determined for the following parameters: somatic cell count, milk composition, bacterial contamination, viability, in vitro phagocytosis and overall killing of Staphylococcus aureus Newbould 305, and cellular chemiluminescence. Because milk sampling occurred throughout lactation, the differences between early, mid- and late lactation were estimated. It was concluded that bacterial contamination was not significantly different in manual milking samples and the reference technique; bacterial contamination was, however, significantly (P < 0.001) higher in machine milking samples than in the reference technique. Among the different sampling techniques, no significant effects on SCC, milk composition, viability and functions of the cells isolated from milk were observed. It was found that viability, intracellular killing and cellular chemiluminescence of milk PMN were significantly lower (P < 0.05) in early lactation compared to mid-lactation. Phagocytosis was significantly (P < 0.05) higher in early lactation compared to mid- and late lactation, and no significant differences were observed between mid and late lactation. From this study, it can be concluded that despite a higher bacterial contamination obtained with the mechanical sampling method, the 3 milk sampling techniques described in this study can be used for the evaluation of milk cell functions. PMID- 11777008 TI - Histochemical detection of the lectin-binding carbohydrates in the zona pellucida during oocyte growth in the wild boar (Sus scrofa scrofa). AB - The changes that occur in the carbohydrate composition of zona pellucida glycoproteins during oocyte maturation in the wild-boar were studied using periodic-acid Schiff (PAS), High Iron Diamine (HID) and Low Iron Diamine (LID). Lectin staining was performed with a panel of 11 HRP-lectin conjugates combined with neuraminidase digestion and chemical treatments. There were few internal glucidic residues, such as N-acetylglucosamine, in the wild boar zona pellucida but there were many subterminal beta-N-acetylgalactosamine, alpha- and beta galactose determinants masked by sialic acid. In addition, beta-N acetylgalactosamine, beta-galactose-(1-3)-N-acetylgalactosamine and beta galactose-(1-4)-N-acetylglucosamine were detected in the sulphated form in the terminal and/or subterminal position. Some differences in the lectin reactive sites occurred in the zona pellucida, depending on the stage of oocyte maturation. PMID- 11777009 TI - Contamination of pigs by nose-to-nose contact or airborne transmission of Salmonella Typhimurium. AB - The aim of this study is to assess the risk of contamination by Salmonella Typhimurium of pigs by nose-to-nose contact or the airborne route. Thirty twelve week-old SPF pigs were divided into 4 groups housed in 4 different rooms: the first room contained Salmonella-free control pigs (n = 4), the second room had 10(3) CFU S. Typhimurium inoculated pigs (n = 5) and non-inoculated "contact" pigs (n = 4), the third room had pigs (n = 8) receiving potentially contaminated air from the following room through a hole (4 pigs housed in the pen situated near the hole and 4 pigs in the pen at the opposite side of the room), and the fourth room had pigs (n = 5) inoculated with 10(6) CFU Salmonella Typhimurium and also non inoculated "contact" pigs (n = 4). The "contact" and the inoculated pigs were housed in adjacent pens allowing nose-to-nose contact. The 5 pigs orally inoculated with 10(6) CFU S. Typhimurium were bacteriologically and serologically positive 1 week later and their environment was contaminated as early as 1 day pi. The faecal samples of 4 nose-to-nose contact pigs were bacteriologically positive and one of them was seropositive 5 weeks pi before the pigs were commingled. The 8 pigs housed in the third room received S. Typhimurium by an active airflow coming from the contaminated room (1000 m3/hour). Their faecal samples remained negative until 8 weeks pi but the environmental swabs taken in the room close to the airinlet were contaminated 2 days pi and positive swabs were found elsewhere in the room 5 weeks pi. Two seropositive pigs were encountered 8 weeks pi in the pen situated near the hole. Only one among the 5 pigs inoculated with 10(3) CFU had bacteriologically positive faeces 1-week pi and the 4 pigs kept in nose-to-nose contact with them remained negative. A dose of 10(3) CFU was too small to induce persistent excretion and to stimulate a humoral immune response. However, the dose of 10(6) CFU induced contamination of nose-to-nose contact pigs and contamination of the environment by airflow. PMID- 11777010 TI - Detection of monokines in paraffin-embedded tissues of pigs using polyclonal antibodies. AB - Monokines are glycoproteins, synthesised by macrophages, which exert various effects on the organism. The most important monokines are interleukin (IL) 1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-6. This paper reports on immunohistochemical techniques developed for the detection of IL-alpha, IL 1beta, IL-6 and TNF-alpha in fixed and paraffin-embedded pig tissues (spleen, lymph nodes, thymus, liver and kidney). Different fixatives (buffered formalin, acetic formalin, paraformadehyde-lysine-periodate and Bouin solution), and antigen unmasking techniques (permeabilisation with Tween 20, pronase enzymatic digestion and microwave-citrate buffer) were used. We describe different protocols for detection of monokines using polyclonal antibodies against the studied monokines. No signal was obtained with monoclonal antibodies against pig TNF-alpha and human IL-1alpha. Bouin solution was shown to be the best fixative for immunohistochemical detection of IL-1alpha, TNF-alpha, and IL-6, using permeabilisation with Tween 20 as an unmasking antigen method. Acetic formalin was shown to be the best fixative for IL-1beta detection, not needing antigen retrieval techniques. Macrophages were identified as the main cytokine-producing cells, although other types of cells also stained positively to some cytokines. These techniques represent valuable tools for studies of the pathogenesis of viral and bacterial diseases, and of the immune system of the pigs. PMID- 11777011 TI - Possible misidentification of Bacteroides sp., probably B. ureolyticus as Taylorella equigenitalis: implications for the laboratory diagnosis of CEM. AB - A wild-type isolate with similar morphological and phenotypic properties to Taylorella equigenitalis, the causative bacterial agent of contagious equine metritis (CEM), was referred for molecular identification by PCR amplification of the 16S rRNA gene. A species-specific PCR failed to yield a product compatible with that of T. equigenitalis. The direct sequencing of the universal 16S rRNA PCR amplicon suggested the presence of a Bacteroides sp., probably Bacteroides ureolyticus, with no consequent effects on the movement and transportation of the animal. Adoption of such a molecular means of identification through sequencing may aid in the identification of the atypical forms of Taylorella equigenitalis, as recently described, as well as differentiating this species from Taylorella asinigenitalis. PMID- 11777012 TI - Apoptosis and necrosis of blood and milk polymorphonuclear leukocytes in early and midlactating healthy cows. AB - Increased milk somatic cell counts (SCC) are used as an indicator for bovine mastitis. During mastitis, polymorphonuclear leukocytes (PMN) become the predominant cell type. Shortly after parturition, the severity of mastitis is increased and several PMN functions are downregulated. Apoptotic and necrotic processes of PMN could influence SCC and PMN functions. In this study, the percentages of apoptotic and necrotic PMN in blood and milk from early and midlactating healthy cows were compared. Apoptosis and necrosis of PMN were quantified using a dual-color flow cytometric procedure with fluorescein labeled annexin-V (green) and propidium iodide (red). Using this technique three different subpopulations of bovine PMN could be detected: apoptotic cells (high intensive green fluorescence), necrotic cells (high intensive green and high intensive red fluorescence) and viable cells (low intensive green and low intensive red fluorescence). Following a 4 h incubation of blood from both groups of cows at 37 degrees C to induce apoptosis, the mean percentage of apoptotic blood PMN was significantly higher (P < 0.01) in early lactating cows (15.1%, n = 9) compared with midlactating cows (5.3%, n = 10). The mean percentage of necrotic PMN remained lower than 5% in all cows. In contrast to blood, no significant difference was found between the percentage of apoptotic PMN in milk from early (41.2%, n = 7) and midlactating cows (34.0%, n = 8). The percentage of necrotic PMN in milk from early lactating cows (25.9%, n = 7) was significantly higher than that in midlactating cows (14.2%, n = 8) (P < 0.05). Higher percentages of apoptotic as well as necrotic PMN were consistently found in milk compared to blood in all cows. From these results, it can be concluded that spontaneously induced apoptosis was higher in blood PMN from early lactating cows than in blood PMN from midlactating cows. The higher percentage of necrotic milk PMN in early lactating cows than in midlactating cows could be explained by the induction of secondary necrosis. PMID- 11777013 TI - Conditional choice-unique outcomes establish expectancies that mediate choice behavior. AB - Conditional discriminative choice tasks can be arranged such that all correct choices yield the same reinforcer or such that each type of correct choice has its own unique reinforcer. The former is the traditional "Common Outcomes" Procedure; the latter is the "Differential Outcomes" Procedure. Use of this Differential Outcomes Procedure facilitates the rate of learning, increases the asymptotic level of performance, and enhances working-memory based performances in both animals and humans. These facts have stimulated many questions and experiments about learning and memory mechanisms and fostered potential applications. PMID- 11777014 TI - In search of the neurobiological underpinnings of the differential outcomes effect. AB - Correlating unique rewards with to-be-remembered events (the Differential Outcomes Procedure [DOP]) enhances learning and memory performance in a range of species. Recently, we have demonstrated that the DOP can be used to reduce or eliminate the learning and memory impairments associated with animal models of amnesia and dementia. This powerful phenomenon, the Differential Outcomes Effect (DOE), has led to the question: How does such a simple manipulation exert such dramatic influence on learning and memory performance? A revised two-process account of the DOE states that using the DOP results in the activation of reward expectancies through Pavlovian mechanisms. The use of unique reward expectancies alters the nature of cognitive processing used to solve discrimination tasks. The change in cognitive processing is represented by utilization of a different memory system than that commonly used to acquire and remember information when a Nondifferential Outcomes Procedure (NOP) is used. Using neurochemical manipulations, it has been demonstrated that different, potentially independent, brain systems modulate memory performance when subjects are trained with a NOP versus a DOP. This memory-based DOP/NOP distinction resembles other dissociative memory theories in which two psychological processes are purportedly served by distinct neurobiological mechanisms. In addition, such results have important ramifications for the treatment of memory disorders because they demonstrate that stimulus and behavioral manipulations, like drugs, can influence neurotransmitter functioning. PMID- 11777015 TI - Differential outcomes training facilitates memory in people with Korsakoff and Prader-Willi syndromes. AB - This article presents evidence that a teaching procedure called differential outcomes training enhances learning and memory. Differential outcomes training reinforces correct responses with outcomes that are unique and specific to the stimuli that are to be remembered. Teaching with this method enhances performance in people with Korsakoff syndrome and people with Prader-Willi syndrome, populations known to have learning and working memory deficits. This initial evidence that persons with learning and memory deficits benefit from differential outcomes training should encourage future work on the development of an intervention using this type of training to aide daily functioning by people with learning and memory impairments. PMID- 11777016 TI - Associations between financial strain and the diurnal salivary cortisol secretion of long-term unemployed individuals. AB - OBJECTIVE: The study investigated the associations between self-rated financial strain and overall diurnal salivary cortisol levels, as well as secretory patterns among long-term unemployed individuals. METHODS: Psychosocial and life style variables were assessed by means of questionnaires among 85 participants (mean age 42+/-9 years; 56% females). Salivary cortisol was sampled on four occasions during a 24-hour period and data was analysed separately for men and women. RESULTS: Among females, high financial strain was related to higher overall cortisol levels, and to elevated levels in the evening. These associations did not reach significance among men. Multivariate analyses showed that evening levels of cortisol were positively associated with financial strain, but largely unrelated to life-style variables and psychological distress. CONCLUSIONS: The results suggest that high financial strain influences the diurnal cortisol secretion of unemployed individuals in terms of elevated cortisol levels in the evening. The mediating mechanisms are in need of further investigation. PMID- 11777017 TI - Classical eyeblink conditioning: clinical models and applications. AB - In this paper, we argue that the main reason that classical eyeblink conditioning has proven so useful when applied to clinical situations, is that a great deal of information is known about the behavioral and neural correlates of this form of associative learning. Presented here is a summary of three lines of research that have used classical eyeblink conditioning to study three different clinical conditions; autism, fetal alcohol syndrome, and obsessive-compulsive disorder. While seemingly very different clinical conditions, classical eyeblink conditioning has proven very useful for advancing our understanding of these clinical pathologies and the neural conditions that may underlie them. PMID- 11777018 TI - Increases in ethanol ingestion by young rats following interaction with intoxicated siblings: a review. AB - Although there are a variety of animal models used in alcoholism research, there has been very little experimental investigation into possible environmental/experiential factors leading to an initial bout of alcohol ingestion. Adolescent alcohol abuse is a major problem in today's society and research is beginning to focus on the predisposing conditions toward alcohol consumption, particularly in this vulnerable age group. The results of recent research from our laboratory are reviewed in which voluntary ingestion of ethanol by preweanling and adolescent rats is increased following exposure to an intoxicated sibling. This paradigm centers on the notion that rodents, and perhaps other mammalian species as well, acquire information about foods to ingest based in part on interaction with a conspecific that has recently ingested a novel diet (e.g. Galef, 1981). Smelling food-derived cues on the breath of another animal is known to affect later food choice. The procedures described in this paper represent a potential new model for examining the effects of early exposure to ethanol through social interactions on the initiation of voluntary alcohol ingestion. PMID- 11777019 TI - A multiple sclerosis cluster associated with a small, north-central Illinois community. AB - The authors investigated a reported incidence cluster of multiple sclerosis (MS) cases in a small, north-central Illinois community to determine validity and statistical significance. DePue, Illinois--a small, north-central Illinois community--has previously been the site of significant environmental heavy-metal exposure from a zinc smelter. Significant contamination of soil and water with zinc and other metals has been documented in this community during the time period of interest. In the mid-1990s, several cases of MS were reported to the Illinois Department of Public Health within the geographic limits of this community. Available medical records from purported MS cases reported to the Illinois Department of Public Health were reviewed, and living individuals were seen and examined. Statistical analyses were conducted with clinically definite MS cases; onset dates were determined by first symptom, and expected incidence rates were determined from published epidemiologic studies. Nine new cases of clinically definite MS occurred among residents of DePue, Illinois, during the period between 1971 and 1990. Seven of the 8 living subjects included in the final analyses were examined by one author (RS). The computed incidence rate deriving from these cases within DePue Township, Illinois, represented a statistically significant excess of new MS cases over expected. During the period from 1971 through 1990, a significant excess of MS cases occurred within the population of DePue, Illinois. Significant exposure of this population to mitogenic trace metals, including zinc, was also documented during this time period. PMID- 11777020 TI - Relation of serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) level to hematological examination results in veterans of Operation Ranch Hand. AB - The authors studied indices of hematologic function and exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) in Vietnam War veterans of Operation Ranch Hand--the Air Force unit responsible for the aerial spraying of Agent Orange and other herbicides in Vietnam. The herbicides were contaminated with TCDD. The authors measured TCDD serum levels in 1987 or later and extrapolated the result to the time of service in Vietnam. The authors studied serum TCDD level in relation to red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, white blood cell count, platelet count, and erythrocyte sedimentation rate at each of 4 physical examinations. Compared with veterans not involved in Operation Ranch Hand, those with the highest TCDD levels in Operation Ranch Hand had mean corpuscular volumes that were about 1% higher and platelet counts that were about 4% higher. These small increases were unlikely to be of clinical significance and may not have been caused by TCDD. PMID- 11777021 TI - Multiple chemical sensitivity: discriminant validity of case definitions. AB - In this study, the authors used the University of Toronto's Health Survey self administered questionnaire to determine discriminant validity of multiple chemical sensitivity definitions. The authors distributed a total of 4,126 questionnaires to adults who attended general, allergy, occupational, and environmental health practices. The authors then matched responses to features selected from existing case definitions posited by Thomson et al.; the National Research Council; Cullen; Ashford and Miller; Randolph; Nethercott et al.; and the 1999 Consensus (references 4-7, 2, 9, and 10, respectively, herein). The overall response rate was 61.7%. The prevalence of reported symptoms was lowest in general practices, was intermediate in occupational health and allergy practices, and was highest in environmental health practices. Features from the definitions presented by Nethercott et al. and the 1999 Consensus (references 9 and 10, respectively, herein) correctly identified more than 80% of environmental health practice patients and more than 70% of general practice patients. Combinations of 4 symptoms (i.e., having a stronger sense of smell than others, feeling dull/groggy, feeling "spacey," and having difficulty concentrating) also discriminated successfully. In summary, features from 2 of 7 case definitions assessed by the University of Toronto Health Survey achieved good discrimination and identified patients with an increased likelihood of multiple chemical sensitivity. PMID- 11777022 TI - Possible sources of sick building syndrome in a Tennessee middle school. AB - Sick Building Syndrome has been reported with increasing frequency during recent years. Buildings that have sustained water damage harbor various molds, some of which may be toxic. Students and staff at Central Middle School in Murfreesboro, Tennessee, reported symptoms similar to those associated with Sick Building Syndrome. Upon investigation, investigators noted that a black fungal growth occurred throughout the building on wet cellulose ceiling tiles. Fungal growth of this type is consistent with the genus Stachybotrys. Stachybotrys spores contain macrocyclic trichothecenes, which may cause harm when inhaled or ingested. Bulk sampling of the black mold was initiated, and the samples were cultured in a moist chamber. Testing of the samples confirmed the presence of Stachybotrys spp., a finding that implies that air sampling procedures should ensue. Professional remediation of this potentially hazardous fungal contaminant is therefore recommended. PMID- 11777023 TI - Health evaluation of volatile organic compound (VOC) emissions from wood and wood based materials. AB - In this study, the authors describe a method for evaluation of material emissions. The study was based on chemical analysis of emissions from 23 materials representing solid wood and wood-based materials commonly used in furniture, interior furnishings, and building products in Denmark in the 1990s. The authors used the emission chamber testing method to examine the selected materials with a qualitative screening and quantitative determination of volatile organic compounds. The authors evaluated the toxicological effects of all substances identified with chamber testing. Lowest concentration of interest and standard room concentrations were assessed, and the authors calculated an S-value for each wood and wood-based material. The authors identified 144 different chemical substances with the screening analyses, and a total of 84 individual substances were quantified with chamber measurements. The irritative effects dominated at low exposure levels; therefore, the lowest concentration of interest and the S-value were based predominantly on these effects. The S-values were very low for solid ash, oak, and beech. For solid spruce and pine, the determining substances for size of the S-value were delta3-carene, alpha-pinene, and limonene. For the surface-treated wood materials, the S-value reflected the emitted substances from the surface treatment. PMID- 11777024 TI - Domestic nitrogen oxide exposure, urinary nitrate, and asthma prevalence in preschool children. AB - A South Australian preschool study carried out in 1993 showed that the prevalence of respiratory symptoms was significantly associated with use of unflued gas appliances for cooking and heating. The authors sought to determine an association between domestic exposure to nitrogen dioxide and the excretion of total urinary nitrate and nitrite, and their association with asthma prevalence. The results indicated that the geometric mean concentrations of nitrogen dioxide were much higher in homes that had natural gas appliance(s) and other types of appliances (i.e., electric and solid fuel). Higher levels of nitrogen dioxide were found in homes of suburban areas with higher prevalence of asthma and respiratory symptoms. Nitrogen dioxide levels were lower in the summer, and there was a higher level in kitchens than in bedrooms. Urinary nitrate excretion was evaluated in 1,335 preschool children from the same sampling areas. No association existed between nitrogen dioxide levels and urinary nitrates, nor was there a relationship between urinary nitrates and asthma prevalence. These findings confirm that there is a positive association between nitrogen dioxide exposure from gas appliances and the prevalence of respiratory symptoms, but urinary nitrate is not a useful biomarker of exposure at these levels. PMID- 11777026 TI - Decreases of natural killer cells and T-lymphocyte subpopulations and increases of B lymphocytes following a 5-day occupational exposure to mixed organic solvents. AB - The authors examined the effects of organic solvents on lymphocyte subpopulations in blood. Natural killer and T-lymphocyte subpopulations and B (CD19+) lymphocytes were measured with flow cytometry in 16 male rotogravure printers on a Friday and on the following Monday. Numbers of all 3 subpopulations of natural killer cells (i.e., CD57+ CD16+, CD57- CD16+, and CD57+ CD16- cells), 2 subpopulations of T lymphocytes (CD4+ CD45RA+ and total CD8+ cells), and total lymphocytes on Friday were significantly fewer than those found on the following Monday. Conversely, the number of B lymphocytes on Friday was significantly larger than the number on Monday. The number of B lymphocytes was significantly correlated with blood toluene levels on Friday. The alteration in the number of CD57+ CD16+ NK cells from Friday to the following Monday was correlated inversely with the corresponding change in exposure level of toluene on Friday. The authors suggest that the effects of mixed organic solvents (primarily toluene) are recoverable decreases of natural killer cells and T lymphocytes and increases in B lymphocytes. PMID- 11777025 TI - Are high-dose toxic exposures always associated with reactive airways dysfunction syndrome (RADS)? AB - Bottling plant workers were evaluated for respiratory symptoms following an accidental exposure to a chlorine dioxide aerosol. Six exposed employees underwent medical and occupational histories, skin testing to common allergens, spirometry before and after use of bronchodilators, and methacholine challenge. The reported exposure to chlorine dioxide ranged from 30 min to 12 hr. Physical examinations were all normal. Four workers had positive prick skin tests to common aeroallergens. None of the workers demonstrated significant changes in forced expiratory volume in 1 sec following use of bronchodilators, and none experienced methacholine hyperresponsiveness. These cases suggest that the occurrence of reactive airways dysfunction syndrome is unpredictable and may not always occur in heavily exposed individuals. PMID- 11777027 TI - Effects of lead on the endocrine system in lead smelter workers. AB - In this study of the effects of lead on the endocrine system, 77 secondary lead smelter workers (i.e., 62 active and 15 retired) were compared with 26 referents. Lead concentrations were determined in plasma with inductively coupled plasma mass spectrometry (i.e., index of recent exposure), in blood with atomic absorption spectrophotometry, and in fingerbone with K x-ray fluorescence technique (i.e., index of long-term exposure). In addition, pituitary hormones were determined in serum by fluoroimmunoassay, and thyroid hormones and testosterone in serum were determined with radioimmunoassay. Nine lead workers and 11 referents were challenged with gonadotrophin-releasing hormone and thyrotrophin-releasing hormone, followed by measurements of stimulated pituitary hormone levels in serum. Median levels of lead in plasma were 0.14 microg/dl (range = 0.04-3.7 microg/dl) in active lead workers, 0.08 microg/dl (range = 0.05 0.4 microg/dl) in retired lead workers, and 0.03 microg/dl (range = 0.02-0.04 microg/dl) in referents (1 microg/dl = 48.3 nmol/l). Corresponding blood lead concentrations were 33.2 microg/dl (range = 8.3-93.2 microg/dl), 18.6 microg/dl (range = 10.4-49.7 microg/dl), and 4.1 microg/dl (range 0.8-6.2 microg/dl), respectively. Respective bone lead levels were 21 microg/gm (range = -13 to 99 microg/gm), 55 microg/gm (range = 3-88 microg/gm), and 2 microg/gm (range = -21 to 14 microg/gm). Concentrations of basal serum hormone (i.e., free thyroid hormones, thyrotrophin, sex hormone binding globulin, and testosterone) were similar in the 3 groups. There were no significant associations between the hormones mentioned herein and blood plasma, blood lead, and bone lead levels. In the challenge test, stimulated follicle-stimulating hormone levels were significantly lower in lead workers (p = .014) than in referents, indicating an effect of lead at the pituitary level. Also, there was a tendency toward lower basal stimulated follicle-stimulating hormone concentrations in lead workers (p = .08). This effect, however, was not associated with blood plasma level, blood lead level, or bone lead level. In conclusion, a moderate exposure to lead was associated with only minor changes in the male endocrine function, particularly affecting the hypothalamic-pituitary axis. Given that sperm parameters were not studied, the authors could not draw conclusions about fertility consequences. PMID- 11777029 TI - Tissue level, distribution, and total body selenium content in healthy and diseased humans in Poland. AB - The authors obtained tissue samples taken at autopsy from 46 healthy individuals killed in accidents and from 75 corpses of victims of various diseases to analyze selenium levels. The per-weight-unit basis of selenium levels (all expressed as ng/gm wet tissue) in tissues decreased in the following order: kidney (469) > liver > spleen > pancreas > heart > brain > lung > bone > skeletal muscle (51). The highest proportion of body selenium was found in skeletal muscles (27.5%); much less selenium was found in bones (16%) and blood (10%). In the tissues of cancer corpses, the selenium levels were much lower than levels in controls. The lowest selenium levels were found in the livers of alcoholics. Tissue selenium levels found in the study were significantly lower than levels reported in Japan, United States, Canada, and other countries. The low selenium levels in the tissues of Polish residents result from inadequate selenium levels in the soil. The authors used selenium levels in tissues to calculate the amount of selenium in humans in Poland (i.e., approximately 5.2 mg). This level was similar to levels found in New Zealand (i.e., 3.0-6.1 mg), but it was lower than the mean level found in Germany (i.e., 6.6 mg) and in the United States (i.e., 13.0-20.3 mg). PMID- 11777028 TI - Health effects of residential exposure to aluminum plant air pollution. AB - In this study, the authors evaluated the relative risk of residential exposure to air pollution from an aluminum plant. The authors used government-compiled data to compare hospital admissions in 1997 for selected respiratory diseases for 2 communities in Brazil. One community, Ouro Preto, was located near an aluminum plant, and the other, Diamantina, was located far from any source of industrial air pollution. The relative risk of hospital admissions for selected respiratory diseases was 4.11 (95% confidence interval = 2.96, 5.70). The risk was highest among individuals between 30 and 39 yr of age (relative risk = 11.70; 95% confidence interval = 1.52, 89.96). Admissions per thousand residents were highest for individuals under 10 yr of age and for individuals older than 70 yr of age. The authors assessed exposure with environmental measurements. Dust deposition was collected in the residences of participants (n = 36 in each location), and the dust was analyzed for aluminum, manganese, magnesium, and calcium content. There were significantly different (p < .05) levels of aluminum in the 2 communities; the highest quantities were found near the aluminum plant. Measurements from independent studies indicated that both 24-hr maximum values and annual mean concentrations of suspended particulate matter exceeded the average of international standards in Ouro Preto (i.e., aluminum plant area). These results suggested that exposure to greater air pollution in the aluminum plant area (i.e., Ouro Preto, Brazil) versus the control area resulted in statistically significant health effects in those individuals who resided in Ouro Preto. PMID- 11777031 TI - Resistance to Varroa destructor (Mesostigmata: Varroidae) when mite-resistant queen honey bees (Hymenoptera: Apidae) were free-mated with unselected drones. AB - This study demonstrated (1) that honey bees, Apis mellifera L, can express a high level of resistance to Varroa destructor Anderson & Trueman when bees were selected for only one resistant trait (suppression of mite reproduction); and (2) that a significant level of mite-resistance was retained when these queens were free-mated with unselected drones. The test compared the growth of mite populations in colonies of bees that each received one of the following queens: (1) resistant--queens selected for suppression of mite reproduction and artificially inseminated in Baton Rouge with drones from similarly selected stocks; (2) resistant x control--resistant queens, as above, produced and free mated to unselected drones by one of four commercial queen producers; and (3) control--commercial queens chosen by the same four queen producers and free-mated as above. All colonies started the test with approximately 0.9 kg of bees that were naturally infested with approximately 650 mites. Colonies with resistant x control queens ended the 115-d test period with significantly fewer mites than did colonies with control queens. This suggests that beekeepers can derive immediate benefit from mite-resistant queens that have been free-mated to unselected drones. Moreover, the production and distribution of these free-mated queens from many commercial sources may be an effective way to insert beneficial genes into our commercial population of honey bees without losing the genetic diversity and the useful beekeeping characteristics of this population. PMID- 11777030 TI - Respiratory symptoms and pulmonary function among traffic police in Bangkok, Thailand. AB - The authors undertook a cross-sectional study of the potential adverse health effects of air pollution in Bangkok, Thailand. During 1998 and 1999, the authors administered lung function spirometry tests and a Thai version of the American Thoracic Society's Division of Lung Diseases (ATS-DLD) respiratory questionnaire to 78 male traffic police and 60 male nontraffic police in Bangkok, as well as to 68 male general police in Ayutthaya province, a rural area in Thailand. No consistent trend of decreased pulmonary function was observed in traffic police. The authors controlled for age, height, and smoking index, after which mean levels of forced expiratory volume in 1 sec and maximal expiratory flow rate in 25% of vital capacity (V25) were significantly lower in Bangkok police than in Ayutthaya police. The prevalence of respiratory symptoms among Bangkok police was slightly higher than among Ayutthaya police. Multiple regression analysis identified age and workplace as statistically significant factors that contributed to the values of forced expiratory volume in 1 sec and V25. This study provided some evidence of an increase in prevalence of obstructive changes in the peripheral airways among traffic police in Bangkok. PMID- 11777032 TI - Optimum timing of miticide applications for control of Varroa destructor (Acari: Varroidae) in Apis mellifera (Hymenoptera: Apidae) in Washington State, USA. AB - Seven treatments for the control of Varroa destructor (Anderson & Trueman) were tested to determine the optimum timing of miticide application. Threshold mite levels indicating miticide application were determined for three possible treatment dates: April, August, and October. The treatments were as follows: (1) fluvalinate in April, (2) fluvalinate in August, (3) fluvalinate in October, (4) fluvalinate in April and October, (5) fluvalinate applied continuously (except during honey flow) with replacement every 42 d, (6) control (no treatment), and (7) coumaphos in April. The number of miticide applications in a season had no effect on brood area or colony bee population a year after initiating the experiment. However, the absence of any treatment significantly reduced brood area and colony bee population and significantly increased colony mite population. Date of treatment had significant effects on colony mortality rates, mite levels, and brood area the following spring. When coupled with sampling and threshold recommendations, a single, late-season application of fluvalinate is as effective for the control of V. destructor as semiannual or continuous miticide applications. Treatment thresholds were recommended for ether roll and 48-h sticky board sampling methods in April (three and 24 mites, respectively) and August (14 and 46 mites, respectively) and for ether rolls in October (three mites) in cold climates. PMID- 11777033 TI - Green peach aphid (Homoptera: Aphididae) action thresholds for controlling the spread of potato leafroll virus in Idaho. AB - Arbitrary green peach aphid, Myzus persicae (Sulzer), action thresholds (0, 5, 10, 20, and 40 aphids per 100 leaves) were tested in 3 yr of field experimentation to determine if they could be maintained and if they would significantly impact aphid densities and limit the incidence of potato leafroll virus (PLRV). In 1997 and 1998, significant linear relationships between thresholds and final percentage of PLRV (expressed as the percentage of tubers infected with PLRV) were observed: there was a trend toward lower PLRV incidence with decreasing action threshold in 1999. There were significant relationships between thresholds and mean number of apterous aphids in 1998 and 1999, indicating that reduction of PLRV resulted from reduced within-field spread by apterae. In almost all cases, aphid densities exceeded threshold levels from one week to the next, clearly showing that the thresholds could not be maintained. Over all experiments, four to nine seasonal applications of methamidophos were warranted by the magnitude of the threshold. Imidacloprid applied at planting to the zero aphid threshold reduced the number of methamidophos applications from nine in the insecticide-at-detection treatment to five. A revised within-field green peach aphid management plan is recommended that includes systemic insecticide applied at planting, aphid sampling every 3-4 d, and foliar insecticide application following aphid detection. PMID- 11777034 TI - Effects of various insecticides on the development of the egg parasitoid Trichogramma dendrolimi (Hymenoptera: Trichogrammatidae). AB - The toxicity of six insecticides, acephate, methomyl, ethofenprox, cartap, chlorfluazuron, and Bacillus thuringiensis (Bt) was tested on different developmental stages of the egg parasitoid, Trichogramma dendrolimi (Matsumura). Each of the insecticides tested showed different degrees of toxicity to the parasitoid, Ethofenprox showed the highest toxicity and cartap showed relatively higher toxicity compared with the other insecticides. The development of the parasitoids treated with these two insecticides was normal, similar to that of the control group. Only the emergence of adult wasps from host eggs was disturbed. Emergence of the host, Mamestra brassicae larva was reduced following treatment with ethofenprox, cartap and methomyl. However, adult female wasps, which emerged from host eggs treated with the insecticides had the ability to oviposit normally. PMID- 11777035 TI - Life table parameters, reproductive rate, intrinsic rate of increase, and estimated cost of rearing Podisus maculiventris (Heteroptera: Pentatomidae) on an artificial diet. AB - The impact of an insect-free artificial diet provided at nymphal and/or adult stage upon the developmental rate, life table parameters, and fertility table parameters was examined for Podisus maculiventris (Say). This study showed that when fed an insect-free artificial diet during both the nymphal and adult stage, developmental time was prolonged, preoviposition period was extended, and reproductive rate (R0) and intrinsic rate of increase (r) were significantly lower than when fed larval insect prey at both nymphal and adult stages. Additionally, feeding larval prey to adults reared as nymphs on an artificial diet significantly increased the proportion of fertile females, the number of eggs laid by mated females, the reproductive rate and intrinsic rate of increase, but the mean generation time was not significantly different. Likewise, feeding artificial diet to adults reared on larval prey resulted in a significant reduction in reproductive rate and intrinsic rate of increase. The "realized" cost to rear P. maculiventris on the artificial diet was calculated (as the cost to double the population size) using raw material cost, fertility table parameters and doubling time values. Raw material cost for rearing P. maculiventris colony on Trichoplusia ni (Hubner) (Lepidoptera: Noctuidae) was only 1.4 times higher than the cost of artificial diet raw materials required to rear the same size colony. However, the realized cost of rearing was 3.5 times higher when rearing on artificial diet because of the prolonged developmental time and reduced reproductive output. The cost efficiency of rearing a beneficial insect on an artificial diet that decreases the intrinsic rate of increase of a colony is discussed, as well as the advantages and disadvantages of supplementing adult diets with natural prey at the reproductive stage. PMID- 11777036 TI - Effect of insecticides used in corn, sorghum, and alfalfa on the predator Orius insidiosus (Hemiptera: Anthocoridae). AB - Orius insidoisus (Say) is an important predator in corn, sorghum, and alfalfa. Foliar insecticides commonly used on corn (permethrin, bifenthrin, and fipronil); sorghum (chlorpyrifos, carbofuran, dimethoate, and cyfluthrin); and both crops (A cyhalothrin and ethyl parathion) were evaluated in 1998 and 1999 for their residual effects on O. insidiosus by caging adults on treated plants at several time intervals: at application (day 0) and 2, 3, and 6 d after application. In addition, imidacloprid, fipronil, and thiamethoxam used as seed treatments on corn and sorghum were tested for their effects on O. insidiosus by caging adults on plants in the presence and absence of greenbugs, Schizaphis graminum (Rondani). Finally, six of the same insecticides that also are used on alfalfa were evaluated in the field for their effects on O. insidiosus and other insects. On day 0, ethyl parathion. bifenthrin, and [lambda]-cyhalothrin on corn caused significantly higher mortality to O. insidiosus than permethrin and fipronil. Ethyl parathion and carbofuran on sorghum caused significantly higher mortality than chlorpyrifos, dimethoate, and A-cyhalothrin, which differed significantly from the control. Mortality with cyfluthrin did not differ significantly from that in the control. Insecticides had no significant effects on O. insidiosus 3 and 6 d after application in 1998 with the exception of permethrin on day 3. Similar patterns of mortality were observed in 1999 experiments. No significant differences in mortality of adults occurred with fipronil and thiamethoxam in the presence and absence of greenbugs. Imidachloprid caused significantly higher mortality to O. insidiosus adults than thiamethoxam or fipronil in some instances when greenbugs were not supplied as food. In alfalfa, the insecticides caused significant mortality to most of the insects evaluated. Ethyl parathion, permethrin, chlorpyrifos, and cyfluthrin caused significantly higher mortality to O. insidiosus than carbofuran and A-cyhalothrin, which differed significantly from the control in 1998. In 1999, all treatments significantly reduced O. insidiosus numbers and did not differ significantly from each other. PMID- 11777037 TI - Interactions between Nosema pyrausta (Microsporidia: Nosematidae) and Bacillus thuringiensis subsp. kurstaki in the European corn borer (Lepidoptera: Pyralidae). AB - Larval susceptibility to Bacillus thuringiensis was determined for Nosema pyrausta-infected and uninfected European corn borers, Ostrinia nubilalis (Hubner), in bioassays using a commercial formulation of B. thuringiensis subsp. kurstaki, Dipel ES, incorporated into diet. LC50 values for N. pyrausta-infected larvae were significantly lower (P<0.0001) than for uninfected larvae and declined with increasing levels of infection. LC50 values for a 15-d bioassay using field-colony first instars were 0.006 and 0.027 mg of Dipel ES/kg of diet for larvae moderately infected by N. pyrausta and uninfected larvae, respectively. Nosema pyrausta-infected larvae reared on Dipel ES-amended diets produced 70-fold fewer spores (P<0.0001) than larvae reared on standard diet. For example, 15 d after placement as first instars on standard diet, infected field colony larvae produced 7.6-8.7 million N. pyrausta spores per larva; similar larvae placed on diet containing 0.09 mg of Dipel ES/kg of diet produced 85-103 thousand spores per larva. Infected larvae also weighed less and failed to mature on Dipel ES-amended diets. Increased susceptibility of N. pyrausta-infected larvae to Dipel ES and reduced N. pyrausta spore production in larvae feeding on diet containing Dipel ES suggest that Bt corn will have a direct adverse effect on the survival and continual impact of N, pyrausta as a regulating factor on European corn borer populations. PMID- 11777038 TI - Dispersal of adult European corn borer (Lepidoptera: Crambidae) within and proximal to irrigated and non-irrigated corn. AB - The European corn borer, Ostrinia nubilalis (Hubner), causes economic damage to corn, Zea mays L., throughout the Corn Belt. Because this insect has become the primary target of Bacillus thuringiensis Berliner (Bt) transgenic corn, current efforts addressing the management of O. nubilalis resistance to Bt corn require information on adult European corn borer dispersal and factors affecting its dispersal. In 1998 we conducted mark-release-recapture, release-recapture, and caged-mating studies to directly measure and compare local dispersal patterns of O. nubilalis adults within and proximal to irrigated and non-irrigated cornfields. Releases of marked adults were made corresponding to the first and second flight of O. nubilalis in eastern Nebraska. Adult dispersal was significantly different between irrigated and non-irrigated cornfields. Released adults tended to remain in and near irrigated cornfields, but dispersed out of and away from non-irrigated cornfields. When released at the edge of the cornfield, neither male nor unmated female O. nubilalis displayed an initial tendency to move out of irrigated corn and into the mixed smooth bromegrass (Bromus inermis Leyss) and broadleaf-weed field edge. Mating efficiency in a late season cornfield was not significantly different than in dense foxtail (Setaria spp.). Generally, we found that adult O. nubilalis dispersal may vary depending on variables such as action-site availability and agronomic practices and their interaction with O. nubilalis life history. PMID- 11777039 TI - Native Vaccinium spp. and Gaylussacia spp. infested by Rhagoletis mendax (Diptera: Tephritidae) in the Great Lakes Region: a potential source of inoculum for infestation of cultivated blueberries. AB - In this study, we addressed the question of whether or not native stands of blueberry (Vaccinium spp.) and/or huckleberry (Gaylussacia spp.) support populations of blueberry maggot, Rhagoletis mendax Curran, in the Great Lakes region. Infestation of commercial blueberries by the blueberry maggot, R. mendax, is a serious problem in many areas where blueberries are grown. In the past 10-20 yr, commercial bighbush blueberry, Vaccinium corymbosum L., production has expanded into places such as southern Ontario and southern Quebec where blueberry maggot had not previously been reported. In the mid-1990s, isolated infestations of commercial highbush blueberry were reported in southern Ontario. Because R. mendax was not considered endemic to that area, it was widely assumed that the pests had come into the fields via movement from exotic localities. Here we present an alternative hypothesis, that the blueberry maggots infesting newly established highbush plantations are derived from native blueberries growing in the vicinity. To test this hypothesis, in 1997-1999, we sampled potential native hosts for R. mendax (Vaccinium spp. and Gaylussacia spp.) from 31 localities in the Great Lakes region, primarily in Michigan and Ontario. R. mendax was reared from fruits of native hosts collected at four sites in Michigan and one site each in Ontario, Indiana, and Ohio. V. corymbosum was the predominant host infested, with infestation of this host observed at five of the seven sites. However, two huckleberry species [Gaylussacia baccata (Wangenheim) K. Koch, and Gaylussacia dumosa (Andersson) Torrey & Gray] had the highest rates of infestation that we observed (25.4 and 17.6%, respectively). These data represent the first published reports of R. mendax infesting native host plants in the Great Lakes region, and support the hypothesis that infestations observed in commercial fields may have originated from infested native host plants. PMID- 11777041 TI - Tunnel formation by Reticulitermes flavipes and Coptotermes formosanus (Isoptera: Rhinotermitidae) in response to wood in sand. AB - The tunneling responses of two subterranean termite species, Coptotermes formosanus Shiraki and Reticulitermes flavipes (Kollar), to the presence of sound wood in laboratory arenas were studied. Branching pattern and the speed of tunnel construction between R. flavipes and C. formosanus also were compared. Patlak's residence index (rho) was generated using the length, width, speed of construction, and area of the primary tunnels built by termites. In the same allotted time, C. formosanus built wider and shorter primary tunnels, whereas R. flavipes built thinner and longer primary tunnels. The presence of wood did not affect termite tunnel formation. This lack of variation in tunnel formation parameters was evidenced by the inability of the termites to locate wood sources over distance, even as short as 2.5 mm, and by the similar tunneling behaviors in areas of the arena with or without wood. Patlak's model predicted the densities of tunnels with an error between 9 and 28%. in experiments with R. flavipes exposed to a range of 0-8,000 g of wood, and between 61 and 87% in experiments with C. formosanus. These results indicated that the residence index can provide a qualitative measure of the effect of habitat heterogeneity on the individual termite tunnels. The tunneling constructions strategy of these subterranean termites is discussed. PMID- 11777040 TI - Response of plum curculio (Coleoptera: Curculionidae) to odor-baited traps near woods. AB - Response of overwintered plum curculios, Conotrachelus nenuphar (Herbst), to odor baited traps was evaluated from the beginning until nearly the end of emigration from overwintering sites in woods. We evaluated clear sticky Plexiglas panels and black pyramid traps placed close to woods adjacent to apple trees in an unsprayed section of an orchard. Traps were baited with aggregation pheromone (grandisoic acid) alone or in combination with one of six synthetic fruit volatiles (benzaldehvde, decyl aldehyde, E-2-hexenal, ethyl isovalerate, hexyl acetate, or limonene). Unbaited traps served as a control treatment. Plum curculio emigration from woods was divided into early-, mid-, and late-season periods based primarily on phenological stage of apple bud and fruit development (tight cluster to bloom, petal fall, and fruit set, respectively). During both early- and late season, panel and pyramid traps baited with benzaldehyde plus pheromone were significantly more attractive than any other traps (baited or unbaited), except panel traps baited with ethyl isovalerate plus pheromone in early season, which likewise captured significantly more adults than unbaited panel traps. During midseason, no lures were significantly attractive, possibly due to prevailing cool weather, unfavorable for adult activity. Over the entire season, panel or pyramid traps baited with benzaldehyde plus pheromone captured nearly six times as many plum curculios as unbaited traps of each type, whereas traps baited with pheromone alone captured about twice as many as unbaited traps of each type. We provide information on sex ratio, female maturity stage, and mating status, and several weather parameters associated with trap captures. We conclude that panel or pyramid traps, or a combination, baited with benzaldehyde plus pheromone placed at borders of plum curculio overwintering sites can be a valuable tool for monitoring the beginning, peak, and end of adult immigration into apple orchards. PMID- 11777042 TI - Ecology and phenology of the boll weevil (Coleoptera: Curculionidae) on an unusual wild host, Hibiscus pernambucensis, in southeastern Mexico. AB - The phenology and ecology of Hibiscus pernambucensis Arruda and its interaction and importance in maintaining populations of the boll weevil, Anthonomus grandis Boheman, were studied over a period of 3 yr in the Soconusco Region of the state of Chiapas, Mexico. H. pernambucensis is a small tree of Neotropical distribution, restricted to lowland areas, and generally associated with halophytic vegetation. This species is found exclusively along the shores of brackish estuaries, in or near mangrove swamps in southeastern Mexico. In this region, H. pernambucensis has a highly seasonal flowering pattern in which the greatest bud production occurs shortly after the start of the rainy season in May and the highest fruit production occurs in July and August. Boll weevil larvae were found in buds of H. pernambucensis during all months but February and densities of buds and weevils were highest from May through September. The percentage of buds infested with boll weevil larvae rarely exceeded 30%. Because plant densities and reproductive output of H. pernambucensis is relatively low and, consequently, the number of oviposition and larval development sites for boll weevils is limited, the importance of this plant as a source of boll weevils with potential of attacking commercial cotton is minimal in comparison with the quantity produced in cultivated cotton. However, the plant could be important as a reservoir of boll weevils in areas of boll weevil quarantine and eradication programs. The factors and circumstances that may have led to this apparent recent host shift of the boll weevil in this region are discussed. PMID- 11777043 TI - Exposure to ginger root oil enhances mating success of irradiated, mass-reared males of Mediterranean fruit fly (Diptera: Tephritidae). AB - Previous research revealed that exposure to ginger root oil, Zingiber officinale Roscoe, containing the known male attractant (a-copaene) increased the mating success of male Mediterranean fruit flies, Ceratitis capitata (Wiedemann), from a newly established laboratory colony. The goal of the current study was to determine whether exposure to ginger root oil likewise enhanced the mating competitiveness of irradiated C. capitata males from a 5-yr-old mass-reared strain. Mating tests were conducted in field cages containing guava trees (Psidium guajava L.) to monitor the mating frequency of irradiated, mass-reared and wild males competing for wild females. In the absence of chemical exposure, wild males outcompeted the mass-reared males and obtained 74% of all matings. However, following exposure to ginger root oil (20 microl for 6 h), the mating frequencies were reversed. Whether exposed as mature (3-d-old) or immature (1-d old) adults, mass-reared males achieved approximately 75% of all matings in tests conducted 2 or 4 d following exposure, respectively. Irradiated, mass-reared males prevented from contacting the oil directly (i.e., exposed to the odor only for 6 h) still exhibited a mating advantage over wild males. In an additional study, signaling levels and female arrivals were compared between males exposed to ginger root oil and nonexposed males, but no significant differences were detected. The implications of these findings for the sterile insect technique are discussed. PMID- 11777044 TI - Field evaluation of a phototoxic dye, phloxine B, against three species of fruit flies (Diptera: Tephritidae). AB - The xanthene dye phloxine B (D&C Red #28) bait was sprayed against fruit flies in mango orchards in 1996 and 1997. The flies used for testing were Mexican fruit fly, Anastrepha ludens (Loew), West Indian fruit fly, Anastrepha obliqua (Macquart), and Mediterranean fruit fly, Ceratitis capitata (Wiedeman). Results of the experiments indicate that the toxic efficacy of phloxine B against these fruit flies is as good as that of malathion-bait sprays. Results also indicate that type of protein used with phloxine B can dramatically influence its efficacy. Hydrolyzed proteins of corn origin, Mazoferm 802 and Nutriplus, and one from microbial origin, Coltec yeast broth, were best. Phloxine B-bait applications as complete coverage or alternate swaths reduced fly populations as well as 19.5 or 9.8% (AI) malathion-Captor 300. Applications of phloxine B bait at concentrations of 0.12% phloxine B reduced populations as well as those applied at 0.48% (AI). The fruit fly parasitoid Diachasmimorpha longicaudata was adversely affected when exposed to phloxine B-Nutriplus bait but not when exposed to the other proteins. PMID- 11777045 TI - Consumption of residue containing cucurbitacin feeding stimulant and reduced rates of carbaryl insecticide by western corn rootworm (Coleoptera: Chrysomelidae). AB - Application of insecticide at a reduced rate with a cucurbitacin-based feeding stimulant is a viable alternative to a broadcast insecticide application for control of adult western corn rootworms, Diabrotica virgifera virgifera, LeConte. Because of the small amount of material applied, it is conceivable that a high density of beetles could consume all of the spray residue before economic control is achieved. A laboratory experiment was conducted to determine the amount of cucurbitacin-based spray residue consumed by beetles. Dried residue of four treatments were exposed to three groups of 10 rootworm beetles for 1 h each. Treatments consisted of a cucurbitacin-based adjuvant (Cidetrak CRW, Trece, Salinas, CA) with carbaryl insecticide (Sevin XLR Plus, Rhone Poulenc, Research Triangle Park, NC) mixed at 0, 0.12, 1.2, and 12 g (AI)/liter. For the treatment with cucurbitacin adjuvant only (no insecticide), beetles consumed 0.029 mg beetle(-1) h(-1) of exposure. Approximately 54% of the beetles were recorded as feeding at any given time during the 60-min feeding period. However, when the spray residue contained carbaryl, no weight loss of treatment residue was measured, though the beetles were observed to feed from the residue during the first few minutes of exposure. When residue included insecticide, beetles quickly ceased feeding (within 20 min), and toxicity behavior was observed 30 min after initial exposure for up to 75% of the beetles, which were classified as moribund (unable to stand upright). Beetle mortality was recorded 24 h after exposure and demonstrated that male beetles (53% dead for three insecticide treatments) were more susceptible to carbaryl toxicity than female beetles (28% dead for three insecticide treatments). Regression analysis showed a significant positive relationship between mortality of female beetles and ovarian development. Based on the measurements of this experiment, it is unlikely that realistic beetle densities would consume enough spray residue to prevent economic control of the beetle population. PMID- 11777046 TI - Distribution, relative importance and effect of lepidopterous borers on maize yields in the forest zone and mid-altitude of Cameroon. AB - Geographic distribution, relative importance, and effect of lepidopterous stem and ear borers on maize, Zea mays L., were studied in the humid forest and the mid-altitude zones of Cameroon from 1994 to 1997. Six villages were chosen in the forest zone and grouped into three blocks representing gradients in human population density. A single block with three villages was chosen in the mid altitude. Farmers' maize fields were surveyed during the vegetative growth phase for Busseola fusca (Fuller) egg batches, and at harvest for number of larvae and pupae by species, plant damage, and ear weight. There was no significant block effect for any of the variables measured, and most of the overall variance (72 99%) was attributed to within-field variability. In the forest zone, the noctuid B. fusca and the pyralid Eldana saccharina (Walker) accounted for >80% of all species in almost all locations, followed by the pyralid Mussidia nigrivenella (Ragonot) and the tortricid Cryptophlebia leucotreta (Meyrick). The noctuid Sesamia calamistis (Hampson) was found in almost all locations during the first season but disappeared in most locations in the second season. B. fusco egg infestation was significantly higher during the second compared with the first season, whereas larval and pupal densities were much higher during the first season. E. saccharina was the predominant species during the second season, when densities increased fourfold. In the mid-altitude, B. fusca was the predominant species. No significant differences in pest densities, plant damage, and ear weight were found between years. Results of stepwise regression of stem and ear damage on pest densities verified the relative importance of the individual species. In the forest zone, ear and stem damage significantly reduced ear weight, whereas in the mid-altitude only stem tunneling was significant. PMID- 11777047 TI - Bollworm (Lepidoptera: Noctuidae) survival on 'Bollgard' and 'Bollgard II' cotton flower bud and flower components. AB - Genetically modified cotton, Gossypium hirsutum L., cultivars ('Bollgard') that produce crystalline proteins from Bacillus thuringiensis (Berliner) are valuable tools for managing lepidopteran insect pests in the United States. However, high numbers of bollworm, Helicoverpa zea (Boddie), larvae have been observed feeding in white flowers of these cultivars. Fresh tissue bioassays were conducted to investigate bollworm survival on Bollgard and 'Bollgard II' cottons. Bollworm survival was higher on square and flower anthers than on other floral structures on 'Deltapine 5415' (conventional cotton) and 'NuCOTN 33B' (Bollgard). Bollworm survival at 72 h was higher on all floral structures from Deltapine 5415 than on corresponding structures from NuCOTN 33B. ELISA tests indicated that CryIA(c) expression varied among plant parts; however, bollworm survival did not correlate with protein expression levels. Trends in bollworm survival on Bollgard II were similar to those on Bollgard and conventional cotton; however, survival was lower on all structures of Bollgard II than on corresponding structures of Bollgard and conventional cotton. These data support field observations of bollworm injury to white flowers and small bolls and provide a better understanding of larval behavior on Bollgard cotton. PMID- 11777048 TI - Mapping of soil insect infestations sampled by excavation and acoustic methods. AB - Geostatistical analysis was used to map traditionally and acoustically sampled populations of soil invertebrates at two different times in a hayfield at Grove Hill, AL, and once in an Auburn, AL, hayfield. The distributions of nearly all the soil invertebrates and their sounds were nonrandom in all three mapping studies. The maps constructed by excavation and acoustic sampling methods were compared by correlating the estimated (kriged) soil invertebrate counts with the estimated (kriged) counts of sounds per minute (pulse rate). Acoustic and traditional estimates were positively correlated in the Auburn study. Kriged estimates for green June beetle grub counts overlapped significantly with kriged estimates of sound pulse rate (R2 = 0.47). Overlap with sound pulse rates increased slightly when other soil organisms were counted along with green June beetle grubs: estimates of sound pulse rates were significantly correlated with counts of all white grubs (R2 = 0.50), all white grubs with earthworms (R2 = 0.52), all white grubs with earthworms and earwigs (R2 = 0.59), and total invertebrates (R2 = 0.59). The correlation between acoustic and traditional estimates was not significant at Grove Hill in either year, possibly because of a lack of experience in signal analysis or because the soil invertebrates may not have generated enough sounds to be detected above the background noise levels. These results suggest that acoustic technology is a promising tool for detecting insect pests in soil, but that further study and additional analysis are needed to improve interpretation of acoustic data obtained in the field. PMID- 11777049 TI - Effect of trichome density on soybean pod feeding by adult bean leaf beetles (Coleoptera: Chrysomelidae). AB - The role of soybean, Glycine max (L.) Merrill, pod trichomes on feeding by adult bean leaf beetles. Cerotoma trifurcata (Forster), was evaluated under laboratory and field conditions during 1997 and 1998. Three Clark isolines and 'Corsoy 79' were used to compare the feeding preference of the beetle on pods with different trichome densities. The three Clark isolines, including densely pubescent, sparsely pubescent, and glabrous, were isogenic except for trichome density. The trichome densities on the pods of Clark densely pubescent, Clark sparsely pubescent, and Corsoy 79 were significantly different. In no-choice tests, under both laboratory and field conditions, the feeding on pods of Clark densely pubescent was significantly lower than that on the other isolines. In the choice test of Corsoy 79 conducted in the laboratory and field, when the trichomes on one of the two pods were shaven off, the feeding on the shaven pods was significantly higher than that of the intact ones. In the choice test among Clark isolines under laboratory condition, the result was significant, with the lowest feeding on the densely pubescent pods. This study demonstrates that densely pubescent soybean has the potential to resist bean leaf beetle feeding on pods. PMID- 11777050 TI - Susceptibility of Diatraea saccharalis (Lepidoptera: Crambidae) to tebufenozide. AB - Dosage-mortality baselines were determined for first and newly molted third instars of the sugarcane borer, Diatraea saccharalis (F.), with tebufenozide incorporated into an artificial diet. Using death as an endpoint for these assays, LC50 and LC90 values were estimated to be 0.17 and 0.41 ppm for the first and 0.87 and 3.67 ppm for third instars, respectively. Developmental effects also were observed and were defined to include mortality as well as physical impairment and retarded or prolonged development with absence of feeding. Concentrations causing developmental effects in treated larvae (EC50 and EC90) were 5.8- and 3.8-fold lower than the LC50 and LC90, respectively. The critical time of exposure to tebufenozide was determined for developmentally synchronous third instars to be less than 12 h postecdysis. Mortality through adult emergence significantly decreased from 92% (treatment at 0 h postecdysis) to 30% (treatment at 12 h postecdysis), when exposed to tebufenozide at the EC50. For surviving larvae, length of development time until pupation was significantly increased and female pupal weight significantly decreased when larvae were treated at 0 h postecdysis into the third instar. In addition, to modifying the traditional ways of assessing mortality 0-3 d postapplication, this study points out the value of using other approaches to pesticide assessment, especially where insect growth regulators are involved. PMID- 11777051 TI - Association of insects and ergot (Claviceps purpurea) in Kentucky bluegrass seed production fields. AB - Insects in Kentucky bluegrass seed production fields in Oregon, Idaho, and Washington were sampled just before harvest and their association with ergot conidia of Claviceps purpurea Fr. (Tul.) was evaluated during 1996-1998. A diversity of insects was observed at all three locations. The most abundant beneficial insects collected with sweep nets were Nysium spp., Nabis spp., ichneumonid wasps, and Hippodamia spp. The cranberry girdler, Chrysoteuchia topiaria (Zeller), was the only important pest on grass seed collected by sweep net. Numbers of aphids such as Sitobion avenae (F.), cicadellids and thrips such as Anaphothrips spp. and Aptinothrips spp. that were collected with all aphid sampler were below economic thresholds. Other insect groups occurred in low numbers. Noctuid moths collected in universal blacklight traps included nine species of cutworms and armyworms. Protogrotis obscura (B. & McD.) was the most common cutworm species and was present in all fields. The moth Chortodes rufostrigata (Pack.) previously reported only from wet meadows in northeast and south central Oregon was found in Kentucky bluegrass fields in central Oregon, suggesting that irrigated Kentucky bluegrass seed production fields may simulate a montane meadow habitat. Conidia of C. purpurea were found on a diversity of insects, including moths, flies, leafhoppers, and thrips. Up to 100% of moths and 75% of flies collected from some fields carried conidia of C. purpurea. No correlation between ergot honeydew present in a field and number of insects with conidia of C. purpurea was detected. PMID- 11777052 TI - Impact of reflective mulch on yield of strawberry plants and incidence of damage by tarnished plant bug (Heteroptera: Miridae). AB - The current study investigated the impact of reflective mulch on yield of strawberry plants and incidence of damage by tarnished plant bugs, Lygus lineolaris (Palisot de Beauvois), for three strawberry cultivars: 'Honeoye', 'Earliglow', and two sibling Dayneutrals ('Tribute' and 'Tristar', herein considered as one cultivar). Of all cultivars tested, Honeoye was the most productive and least susceptible to tarnished plant bug. For Earliglow and Honeoye, reflective mulch enhanced productivity of strawberry plants and suppressed density of nymphs per flower cluster and proportion of damaged fruits, but did not significantly impact numbers of nymphs or damaged fruits per hectare, Results with Dayneutrals were not consistently significant. Both in the presence or absence of reflective mulch, proportion of damaged fruits increased with increasing density of nymphs per flower cluster and with decreasing number of fruits harvested per row section, suggesting that planting productive strawberry cultivars or maintaining cultural practices that promote high yield may provide an effective line of defense against tarnished plant bug. These results also suggest that reflective mulch may suppress incidence of damage by tarnished plant bug both directly, by reducing number of nymphs per flower cluster, and indirectly, by enhancing productivity of strawberry plants. Economic analyses evaluating costs and benefits of using reflective mulch, as well as studies investigating mechanisms that underlie the impact of reflective mulch on yield and incidence of damage by tarnished plant bug, are still needed before reflective mulch can be implemented as a management strategy in commercial strawberry fields. PMID- 11777053 TI - Nonwoven fiber barriers for control of cabbage maggot and onion maggot (Diptera: Anthomyiidae). AB - We investigated the use of nonwoven fiber barriers for control of cabbage maggot, Delia radicum (L.), and onion maggot, D. antiqua (Meigen). The barriers consist of arrangements of minute fibers loosely intertwined in "web" form. Results from a greenhouse experiment showed that manually applied graphite fibers placed at the base of broccoli plants reduced the number of D. radicum eggs by 64-98%, and that efficacy increased with greater fiber density. Using a melt extrusion process, we devised a method for on-site creation of nonwoven fibers of ethylene vinyl acetate (EVA). In field trials with broccoli and onion plants, EVA fibers significantly reduced the number of cabbage and onion maggots infesting plants. Fiber barriers provided comparable control to standard insecticide applications. The addition of blue, yellow, red, or black pigments, as well as optical brighteners that absorb UV light did not enhance fiber efficacy. Incorporation of capsaicin olfactory repellent to EVA also did not enhance fiber efficacy. Nonwoven fiber barriers may offer an alternative to insecticides for control of cabbage maggot and onion maggot and possibly other insect pests. Additional research is needed to improve the application process and to identify economically feasible and biodegradable compounds for fibers. PMID- 11777054 TI - Plant washing as a pest management technique for control of aphids (Homoptera: Aphididae). AB - Changes in aphid presence following plant washings were evaluated on hibiscus plants, Hibiscus rosa-sinensis L., that supported natural aphid infestations- primarily melon aphid, Aphis gossypii Clover. Type of plant module (such as stems, tight buds, open flowers, and sepal caps) and percent of module's surface covered by aphids were recorded for each branch tip on every plant. Plant washing was done with tap water, applied for 30 s three times a week for 3 wk. Aphid presence was recorded each week. Aphid presence on plant structures immediately before and after a single 30-s wash treatment was also examined. In the 3-wk study, mean percent coverage of plant parts with aphids was significantly affected by wash treatment, plant module type, and their interactions, as well as by time and the interaction of time with wash treatment. By the third week, unwashed plants had 33.1% of stems and branch tips scoring >5% coverage with aphids, and 17.9% of unwashed stems and branch tips had 20% or more of their surface area covered by aphids. Washing plants prevented aphid coverage from ever exceeding the 5% class on all module types. In the second experiment, buds and stems with high numbers of aphids before washing generally experienced notable declines with a single wash. When the prewash coverage was 10% or greater, reduction in coverage ranged from 50 to 100% of the prewash amount. In 64% of the cases, the reduction in coverage was 75% or more of the prewash amount. Plant washing can provide a viable means of management for small, soft-bodied arthropods such as aphids. PMID- 11777055 TI - Field attraction of the stink bug Euschistus conspersus (Hemiptera: Pentatomidae) to synthetic pheromone-baited host plants. AB - The attraction of the stink bug Euschistus conspersus Uhler to sources of the synthetic pheromone component methyl (2E,4Z)-decadienoate was investigated in a series of field experiments in native vegetation surrounding commercial apple orchards in Washington. In experiments with pheromone lures placed inside two different tube-type traps, stink bugs were attracted to the immediate area around traps in large numbers, but very few were caught in the traps. Pheromone lures attached directly to the host plant mullein, Verbascum thapsus L., demonstrated that these 'baited" plants attracted significantly more E. conspersus than unbaited plants. Spring (reproductive) and summer (reproductively diapausing) E. conspersus adults, both males and females, were attracted to pheromone-baited plants. There was no significant difference in the number of male or female E. conspersus attracted to pheromone-baited traps or plants in any of the experiments, further characterizing methyl (2E,4Z)-decadienoate as an aggregation, and not a sex pheromone. Stink bug aggregations formed within 24-48 h of lure placement on mullein plants and remained constant until the lure was removed after which aggregations declined over 3-4 d to the level of unbaited plants. The implications of these studies for E. conspersus monitoring and management are discussed. PMID- 11777056 TI - Seasonal flight activity of two Homalodisca species (Homoptera: Cicadellidae) that spread Xylella fastidiosa in southern California. AB - Homalodisca coagulata (Say) and Homalodisca lacerta (Fowler) are vectors of a new bacterial disease of oleander in California known as oleander leaf scorch, induced by the bacterium Xylella fastidiosa. H. coagulata also has been implicated in the spread of the strain of X. fastidiosa that induces Pierce's disease of grapevines in California. We monitored the flight activity of H. coagulata and H. lacerta in oleander and citrus by using yellow sticky cards at three southern California locations where outbreaks of oleander leaf scorch have been documented, and where vector compliments are different. Areas sampled included a mesic coastal area (Irvine, CA) that supports predominantly H. coagulata and few H. lacerta, a dry inland location (Palm Desert, CA) that supports predominantly H. lacerta and few H. coagulata, and an intermediate area (Riverside, CA) supporting both Homalodisca species. From November 1996 to October 1999 peak catches of both Homalodisca species occurred during the midsummer at all locations. H. coagulata was trapped in greater numbers in citrus than in oleander at both the Riverside and the Irvine sites. Likewise, H. lacerta in Riverside was more associated with citrus than oleander, yet H. lacerta in Palm Desert was trapped in greater numbers in oleander than citrus. PMID- 11777057 TI - Overwintering of codling moth (Lepidoptera: Tortricidae) larvae in apple harvest bins and subsequent moth emergence. AB - Codling moths, Cydia pomonella (L.), have long been suspected of emerging from stacks of harvest bins in the spring and causing damage to nearby apple and pear orchards. With increased use of mating disruption for codling moth control, outside sources of infestation have become more of a concern for growers using pheromone based mating disruption systems. Studies were designed to provide information on bins as a source of codling moth and the pattern of codling moth emergence from stacks of bins. In these studies, codling moth larvae colonized wood harvest bins at a much higher frequency than harvest bins made of injection molded plastic (189 moths emerged from wood compared with five from plastic). There was no statistical difference in the number of moths infesting bins that had been filled with infested fruit compared with bins left empty at harvest. This suggests that codling moth enter the bins during the time that the bins are in the orchard before harvest. Emergence of laboratory reared adult codling moth from wood bins placed in stacks was found to be prolonged compared with field populations. Temperature differences within the bin stacks accounted for this attenuated emergence pattern. Covering bin stacks with clear plastic accelerated codling moth development in the upper levels of the stack. Codling moth emergence patterns from plastic-covered stacks more closely coincided with male flight in field populations. This information could be important in developing a technique for neutralizing codling moth-infested bins, and in understanding how infested bins may influence pest management in fruit orchards that are located near bin piles. Implications for control of codling moth in conventional orchards and in those using mating disruption as the principal component of an integrated pest management system include increased numbers of treatments directed at areas affected by infested bins. PMID- 11777058 TI - A computerized system for remote monitoring of subterranean termites near structures. AB - Sensors comprising wooden stakes painted with conductive circuits of silver particle emulsion were inserted in Sentricon stations in soil near structures. Sensors were wired to a datalogger that was programmed to test for circuit breakage every 2 h and store the data in its memory. A host computer was programmed to access the datalogger through telephone communication lines for data download every 4 d. The computerized monitoring system was tested in three remote sites, and site visits were conducted monthly for 6 mo to examine system accuracy in detecting termite activity. The mean monthly accuracy for the system to correctly report the presence (true positive) or absence of termites (true negative) in the stations was 85%, but the accuracy at 6 mo after system installation ranged from 41 to 79%. Mean sensor longevity, defined as the time for a sensor circuit to break in the absence of termites, was approximately 4.4 mo. PMID- 11777059 TI - Effects of aromatic cedar mulch on the Argentine ant and the odorous house ant (Hymenoptera: Formicidae). AB - In laboratory studies, the Argentine ant, Linepithema humile (Mayr), and the odorous house ant, Tapinoma sessile (Say), avoided aromatic cedar mulch as a nesting substrate. Both ant species were killed when confined with fresh aromatic cedar mulch in sealed containers. However, when confined with cedar mulch that had been aged outdoors for up to 140 d, mortality of L. humile was complete regardless of mulch age, whereas T. sessile mortality declined significantly over the mulch-aging period. Argentine ant susceptibility to aromatic cedar mulch was also greater than that of the odorous house ant when colonies were restricted to mulch in open trays. In addition, commercial aromatic cedar oil was lethal to both ant species. Our results suggest that aromatic cedar mulch may serve as an effective component of a comprehensive urban ant management program. PMID- 11777060 TI - Efficacy of vetiver oil and nootkatone as soil barriers against Formosan subterranean termite (Isoptera: Rhinotermitidae). AB - Vetiver oil and its components nootkatone and cedrene were assessed as sand treatments for their efficacy to disrupt food recruitment by Coptotermes formosanus Shiraki. Termites were required to tunnel through sand treated with vetiver oil, nootkatone, cedrene, or untreated sand to reach a food source. Results showed that sand treated with vetiver oil or nootkatone disrupted termite tunneling behavior. As a consequence, after 21 d, wood consumption and termite survival were significantly lower compared with cedrene-treated or untreated sand treatments. Sand treated with vetiver oil or nootkatone at 100 microg/g substrate were effective barriers to termites. PMID- 11777061 TI - Inter-regional differences in baseline toxicity of Bemisia argentifolii (Homoptera: Aleyrodidae) to the two insect growth regulators, buprofezin and pyriproxyfen. AB - A survey of 53 Bemisia argentifolii Bellows & Perring populations from different agricultural regions in California and Arizona was conducted from 1997 to 1999 to establish baseline toxicological responses to buprofezin and pyriproxyfen. Although both compounds proved to be highly toxic even in minute quantities to specific stages, geographical and temporal differences in responses were detected using a leaf spray bioassay technique. Monitoring for three years revealed that six to seven populations had higher LC50 values but not greater survival when exposed to these two insecticides. A significant difference in relative susceptibility to buprofezin was first observed in late season 1997 in San Joaquin Valley populations with LC50s ranging from 16 to 22 microg (AI)/liter(-1) compared with IC50s of 1 to 3 mg (AI)/liter(-1) in Imperial, Palo Verde Valley and Yuma populations. Whiteflies collected in subsequent years from these and other locations showed an increase in susceptibility to buprofezin. Regional differences in susceptibilities to pyriproxyfen were minimal within the same years. Three years of sampling revealed consistently higher LC50s to pyriproxyfen in populations from Palo Verde Valley, CA, compared with whiteflies from Imperial, San Joaquin Valley or Yuma. As was the case with buprofezin, a decline in LC50s to pyriproxyfen was observed in whiteflies from all locations sampled in 1999. However, no correlation was observed between buprofezin and pyriproxyfen toxicity in any of the strains. The variable toxicities observed to both compounds over a period of 3 yr may be due principally to inherent differences among geographical populations or due to past chemical use which may confer positive or negative cross-resistance to buprofezin or pyriproxyfen. PMID- 11777062 TI - Different cross-resistance patterns in the diamondback moth (Lepidoptera: Plutellidae) resistant to Bacillus thuringiensis toxin Cry1C. AB - Two strains of the diamondback moth, Plutella xylostella (L.), were selected using Cry1C protoxin and transgenic broccoli plants expressing a Cry1C toxin of Bacillus thuringiensis (Bt). Both strains were resistant to Cry1C but had different cross-resistance patterns. We used 12 Bt protoxins for cross-resistance tests, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Bb, Cry1C, Cry1D, Cry1E, Cry1F, Cry1J, Cry2Ab, Cry9Aa, and Cry9C. Compared with the unselected sister strain (BCS), the resistance ratio (BR) of one strain (BCS-Cry1C-1) to the Cry1C protoxin was 1,090-fold with high level of cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1F, and Cry1J (RR > 390-fold). The cross-resistance to Cry1A, Cry1F, and Cry1J in this strain was probably related to the Cry1A resistance gene(s) that came from the initial field population and was caused by intensive sprayings of Bt products containing Cry1A protoxins. The neonates of this strain can survive on transgenic broccoli plants expressing either Cry1Ac or Cry1C toxins. The other strain (BCS-Cry1C-2) was highly resistant to Cry1C but not cross resistant to other Bt protoxins. The neonates of this strain can survive on transgenic broccoli expressing Cry1C toxin but not Cry1Ac toxin. The gene(s) conferring resistance to Cry1C segregates independently from Cry1Ac resistance in these strains. The toxicity of Cry1E and Cry2Ab protoxins was low to all of the three strains. The overall progress of all work has resulted in a unique model system to test the stacked genes strategy for resistance management of Bt transgenic crops. PMID- 11777063 TI - Selection, egg viability, and fecundity of the sugarcane borer (Lepidoptera: Crambidae) with tebufenozide. AB - Two separate attempts to select the sugarcane borer, Diatraea saccharalis (F.), for resistance to tebufenozide were unsuccessful. Both selected colonies were lost after the fourth generation due to a lack of oviposition. Differences were not detected in fecundity or percent egg viability for 5-d-old third instars exposed to concentrations (EC5, EC15, and EC30) of tebufenozide for 7 d. Decreases (P < or = 0.01) in mean female pupal weights were detected in larvae exposed to EC15 and EC30 concentrations. An ovicidal impact using serial dilutions of tebufenozide (10, 100, and 200 ppm) also was detected. Percent viability was reduced from 98% for untreated eggs to 61% for eggs dipped in 10 ppm and below 6% for eggs dipped in > or = 100 ppm. Eggs treated with 200 ppm did not hatch. Though some embryonic development was observed on eggs treated with the high concentrations (100 and 200 ppm), sclerotization of head capsule was not apparent. The ovicidal property of tebufenozide may enhance its effectiveness in controlling populations of the D. saccharalis on an area-wide basis. Fecundity and egg viability were affected in later generations of selection; however, separate studies assessing individuals that were exposed to sublethal concentration (EC5, EC15, and EC30) of tebufenozide as third instars for 7 d in one generation did not detect differences. PMID- 11777064 TI - Monitoring butocarboxim resistance of the woolly whitefly (Homoptera: Aleyrodidae) in citrus from Valencia, Spain. AB - Glass vials coated internally with an insecticide were used as a resistance monitoring technique for testing field populations of the woolly whitefly, Aleurothrixus floccosus (Maskell), collected from citrus. The distribution of resistance to the insecticide butocarboxim in citrus orchards from Valencia (Spain) during 1993 and 1994 was determined by means of this technique. Adults resting on citrus shoots were captured with a portable vacuum cleaner and introduced into the vials. The technique provides control mortality of <25% when assessed 7 h after the insects are captured. In 21 populations tested, LC50s ranged from 1.8 to 42.3 mg/ml. This represents resistance ratios >20-fold among populations. Lower slopes of the concentration-mortality line were found in whitefly populations that exhibited a low level of the LC50. Resistance was widespread in the Valencia areabut spatially irregular, with nearby orchards occasionally showing wide differences in resistance levels. The levels of resistance to butocarboxim obtained with this technique closely matched the field efficacy of the insecticide. This residue bioassay provides a convenient and rapid method to monitor insecticide resistance in A. floccosus populations. PMID- 11777065 TI - Chronic exposure of the European corn borer (Lepidoptera: Crambidae) to Cry1Ab Bacillus thuringiensis toxin. AB - Transgenic corn expressing the insecticidal toxin from Bacillus thuringiensis Berliner is gaining support as an effective control technology for use against lepidopteran pests, particularly European corn borer, Ostrinia nubilalis Hubner (Lepidoptera: Crambidae). However, there is concern that widespread adoption of transgenic plants will rapidly lead to B. thuringiensis toxin resistance. Thus, long-term selection of O. nubilalis populations with the Cry1Ab B. thuringiensis toxin has been undertaken in several laboratories in the United States and in Europe. We present results from two independent selection experiments performed in laboratories at the University of Nebraska and at the Institut National de la Recherche Agronomique in France. Although the protocols and methods used by the two laboratories were different, the results were comparable. The highest level of resistance occurred at generation 7 (14-fold), generation 9 (13-fold), and generation 9 (32-fold) for three different strains. For each strain, the level of resistance fluctuated from generation to generation, although there were consistently significant decreases in toxin susceptibility across generations for all selected strains. These results suggest that low levels of resistance are common among widely distributed O. nubilalis populations. PMID- 11777066 TI - Fitness costs and maternal effects associated with resistance to transgenic cotton in the pink bollworm (Lepidoptera: Gelechiidae). AB - Transgenic cotton producing a Bacillus thuringiensis (Bt) toxin is widely used for controlling the pink bollworm, Perctinophora gossypiella (Saunders). We compared performance of pink bollworm strains resistant to Bt cotton with performance of their susceptible counterparts on non-Bt cotton. We found fitness costs that reduced survival on non-Bt cotton by an average of 51.5% in two resistant strains relative to the susceptible strains. The survival cost was recessive in one set of crosses between a resistant strain and the susceptible strain from which it was derived. However, crosses involving an unrelated resistant and susceptible strain indicated that the survival cost could be dominant. Development time on non-Bt cotton did not differ between the two related resistant and susceptible strains. A slight recessive cost affecting development time was suggested by comparison of the unrelated resistant and susceptible strains. Maternal effects transmitted by parents that had eaten Bt treated artificial diet as larvae had negative effects on embryogenesis, adult fertility, or both, and reduced the ability of neonates to enter cotton bolls. These results provide further evidence that fitness costs associated with the evolution of resistance to Bt cotton are substantial in the pink bollworm. PMID- 11777067 TI - Cross-resistance, inheritance, and biochemistry of mitochondrial electron transport inhibitor-acaricide resistance in Tetranychus urticae (Acari: Tetranychidae). AB - Resistance of the twospotted spider mite, Tetranychus urticae Koch, to acaricides acting as mitochondrial electron transport inhibitors (METIs) is an increasing problem. Because of their high levels of cross-resistance to all commercially available METI-acaricides, a Japanese strain (AKITA) and an English strain (UK 99) of T. urticae were investigated in detail. Larvae of both strains, AKITA and UK-99, showed 1,100- and 480-fold resistance against pyridaben, 870- and 45-fold resistance against fenpyroximate, and 33- and 44-fold resistance against tebufenpyrad, respectively, in a foliar spray application bioassay compared with the susceptible strain GSS. These resistance factors remained stable even when maintained in the laboratory without further selection. Furthermore, strain AKITA showed cross-resistance to dicofol. The METI resistant strains AKITA and UK-99 showed 2.4- and 1.7-fold enhanced O-ethoxycoumarin O-deethylation (cytochrome P450) activity. Increased oxidative metabolism of the METI-acaricides in the resistant strains could be partially suppressed in vivo by the monooxygenase inhibitor piperonyl butoxide. Reciprocal crosses of homozygous, diploid females and hemizygous, haploid males of strains GSS (susceptible) and AKITA (resistant) revealed that resistance to pyridaben and fenpyroximate was inherited incompletely dominant with slight differences between maternal and paternal inheritance. This is the first attempt to mechanistically describe METI-acaricide resistance in T. urticae. The implications for resistance management strategies are discussed. PMID- 11777068 TI - Isolation of a deet-insensitive mutant of Drosophila melanogaster (Diptera: Drosophilidae). AB - Despite the widespread use of N,N,-diethyl-3-methylbenzamide (deet) in insect repellent products, nothing is known about the molecular basis for the repellency of deet, we initiated a molecular genetics program to elucidate the molecular mechanism of deet repellency in Drosophila melanogaster (Meigen). Deet repellency was apparently due to airborne vapors, as wild type flies were repelled by a deet treated surface in the absence of physical contact and in the dark. A mutant was isolated using chemical mutagenesis and at choice assay. In a choice assay, mutant flies entered 82 +/- 1% of deet-containing tubes, whereas wild type flies entered only 6 +/- 2% of deet-containing tubes. The mutant was repelled by other repellents, benzaldehyde and citronellal. The mutation was recessive and located on the X chromosome. PMID- 11777069 TI - Field efficacy and seasonal expression profiles for terminal leaves of single and double Bacillus thuringiensis toxin cotton genotypes. AB - Examination of commercial Cry1Ac transgenic Bacillus thuringiensis Berliner (Bt) cotton varieties (Bollgard, Monsanto, St. Louis, MO) and an experimental Cry1Ac + Cry2Ab transgenic Bt cotton variety (Bollgard II, Monsanto) for lepidopteran field efficacy was conducted during the 2000 growing season. In addition, a commercially available (Envirologix, Portland, ME) quantification assay (ELISA) was used to measure and profile the expression levels of Cry proteins in two of these varieties ['DP50B, Bollgard'; 'DP50BII, Bollgard II' (Delta & Pine Land, Scott, MS)]. Populations of beet army worms, Spodoptera exigua (Hubner), and soybean loopers, Pseudoplusia includens (Walker), were significantly lower (P < 0.05) in Bollgard II plots compared with Bollgard. Population numbers for fall army worms, Spodoptera frugiperda (J. E. Smith), and salt marsh caterpillars, Estigmene acrea (Drury), were lower in Bollgard II plots compared with Bollgard but means did not differ significantly (P > 0.05). Single and dual-toxin genotypes remained superior (P < 0.05) compared with conventional cotton against the tobacco budworm, Heliothis virescens (F.). The addition of Cry2Ab had no significant (P > 0.05) impact on Cry1Ac expression in Bollgard II compared with Cry1Ac expression in Bollgard. Furthermore, throughout the season Cry2Ab was present at much higher levels in the plant compared with Cry1Ac for Bollgard II plants. Possible species-specific reasons for increased efficacy of Bollgard II over Bollgard are discussed. PMID- 11777070 TI - Field resistance of two soybean germplasm lines, HC95-15MB and HC95-24MB, against bean leaf beetle (Coleoptera: Chrysomelidae), western corn rootworm (Coleoptera: Chrysomelidae), and Japanese beetles (Coleoptera: Scarabaidae). AB - Two recently released, Mexican bean beetle, Epilachna varivestis, Mulsant, resistant soybean, Glycine max (L.) Merrill, germplasm lines, HC95-15MB and HC95 24MB, were examined for foliar and pod feeding resistance to adult bean leaf beetles, Cerotoma trifurcata (Forster), western corn rootworms, Diabrotica virgifera virgifera LeConte, and Japanese beetles, Popillia japonica Newman. Both lines were planted along with a susceptible control cultivar in 18 by 30-m plots and separate 0.8-ha size fields. Insects were sampled on a weekly basis with a sweep net. In late summer, defoliation ratings were recorded along with data on percentage pod feeding. Although a few significant differences in insect densities were obtained among the soybean lines on some sampling dates, no specific trends were observed in the ability of the resistant germplasm to reduce insect numbers. Insect population densities were similarly on all lines. However, both resistant lines were able to reduce defoliation during the growing season. Conversely, percentage pod feeding was similar among all the soybean lines, with no differences observed. The resistant germplasm lines appear able to lower levels of defoliation, and thus, offer a potential management tactic where leaf feeding, i.e., defoliation, is of concern. However, their ability to greatly reduce beetle population densities, and for the bean leaf beetle, to reduce pod feeding, appears limited. PMID- 11777071 TI - Estimating relative decline in populations of subterranean termites (Isoptera: Rhinotermitidae) due to baiting. AB - Although mark-recapture protocols produce inaccurate population estimates of termite colonies, they might be employed to estimate a relative change in colony size. This possibility was tested using two Australian, mound-building, wood eating, subterranean Coptotermes species. Three different toxicants delivered in baits were used to decrease (but not eliminate) colony size, and a single mark recapture protocol was used to estimate pre- and postbaiting population sizes. For both species, the numbers of termites retrieved from bait stations varied widely, resulting in no significant differences in the numbers of termites sampled between treatments in either the pre- or postbaiting protocols. There were significantly fewer termites sampled in all treatments, controls included, in the postbaiting protocol compared with the pre-, suggesting a seasonal change in forager numbers. The comparison of population estimates shows a large decrease in toxicant treated colonies compared with little change in control colonies, which suggests that estimating the relative decline in population size using mark recapture protocols might to be possible. However, the change in population estimate was due entirely to the significantly lower recapture rate in the control colonies relative to the toxicant treated colonies, as numbers of unmarked termites did not change between treatments. The population estimates should be treated with caution because low recapture rates produce dubious population estimates and, in some cases, postbaiting mark-recapture population estimates could be much greater than those at prebaiting, despite consumption of bait in sufficient quantities to cause population decline. A possible interaction between fat-stain markers and toxicants should be investigated if mark-recapture population estimates are used. Alternative methods of population change are advised, along with other indirect measures. PMID- 11777072 TI - Mechanical barrier for preventing climbing by lesser mealworm (Coleoptera: Tenebrionidae) and hide beetle (Coleoptera: Dermestidae) larvae in poultry houses. AB - Mechanical barriers consisting of bands of polyethylene terepthalate resin attached to wooden posts by latex caulk adhesive and staples were 100% effective in preventing passage of dispersing lesser mealworm, Alphitobius diaperinus (Panzer), larvae in the laboratory. Barriers continued to be 100% effective after beinig held in a caged layer poultry house for 3 mo. Polyethylene terepthalate barriers installed on support posts in a pullet house in Brooker, FL, were >92% effective against natural populations of lesser mealworm larvae 6 mo after installation. The barriers also were >94% effective against natural populations of larvae of the hide beetle, Dermestes maculatus DeGeer, when fly populations were low. Fecal spot depositions by house flies in excess of 31 cumulative fly spots per square centimeter on spot cards reduced the effectiveness of the barriers to 79-90%, and barrier efficacy was reduced to 40-56% when fly spots covered >80% of the surface of the plastic. Washing the barriers with water to remove fly spots restored their effectiveness against hide beetle larvae to >99%. PMID- 11777073 TI - Evaluation of a sampling trap for Dermanyssus gallinae (Acari: Dermanyssidae). AB - Traps made by rectangular pieces of 3 mm thick corrugated cardboard of four different sizes, 200 by 140 (A), 140 by 100 (B), 100 by 70 (C), and 200 by 40 mm (D), were evaluated as a sampling device for the chicken mite, Dermanyssus gallinae (De Geer). Mites were trapped during 2, 4, 6, 8, and 10 d, respectively, in a poultry house heavily infested with the parasite. Significantly greater numbers of mites were collected by trap B. Additionally, significantly more mites were collected during the sampling periods 6-10 d than by 2 and 4 d. However, with regard to trap size and sampling period, trap C, used for 2 d, collected significantly more mites per day and trap area than any of the other traps. Therefore, such a trap was suggested for monitoring population trends of chicken mites in poultry houses. The larger traps contained significantly higher numbers of mites per trap and may therefore be feasible to use in alternative, nonchemical control programs. Optimum sample size, or number of traps required to monitor population trends of D. gallinae, was also calculated. At a relative variability of 20%, and at densities of 2,000-20,000 mites per trap, approximately 11-16 of trap B and 11-19 of trap C would be adequate to monitor mites. PMID- 11777074 TI - The Ivomec SR Bolus for control of Boophilus annulatus (Acari: Ixodidae) on cattle in South Texas. AB - When Hereford heifers infested with Boophilus annulatus (Say) were treated with a single Ivomec SR Bolus, the concentration of ivermectin in the serum of the treated cattle reached a maximum of 8.8 +/- 0.9 ppb at 2 wk posttreatment. The single bolus treatment resulted in 84.4% control of standard engorging B. annulatus females on treated cattle over the 20-wk trial. Although fewer engorged ticks were collected from the sentinel heifers exposed in the treated pasture than those in the control pasture at weeks 4, 10, and 16 posttreatment, none of the differences was statistically significant. Each exposure of sentinel cattle found free-living ticks in both the treated and control pastures, indicating the infestation was not eliminated by the treatment. When the trial was repeated using two Ivomec SR Boluses/heifer, the concentration of ivermectin in the serum of the treated cattle reached a maximum level of 31.2 +/- 3.9 ppb at week 13 posttreatment. The use of two boluses/heifer resulted in 99.6% control of standard engorging B. annulatus females over the 20-wk trial. No ticks were found on sentinels placed in the treated pasture after week 9 posttreatment, an indication that the treatment had eliminated the free-living population in the treated pasture. From these studies, we conclude that a single Ivomec SR Bolus is incapable of sufficient control of B. annulatus to meet the rigid requirements of the Cattle Fever Tick Eradication Program in South Texas. Although two boluses per animal did eliminate the ticks from treated heifers and the pasture they were in, the treatment would not be sufficiently efficacious for mature cattle (>400 kg) for it to be useful in the program. PMID- 11777075 TI - Role of school schedule, age, and parental socioeconomic status on sleep duration and sleepiness of Parisian children. AB - The aim of the study was to assess the duration and quality of sleep of prepubertal (Tanner Scale level 1) physically and mentally healthy children as a function of school schedule (4 versus 4.5 days per week), age and grade (median age of 9.5 years for 4th grade versus median age of 10.5 years for 5th grade), school district (wealthy versus nonwealthy) in Paris, France, and parental socioeconomic status (high, medium, or low). We studied 51 girl and 44 boy volunteer pupils with written parental consent. The study lasted 2 weeks during the month of March. During the first study week, the children attended school 4.5 days, and during the second week, they attended school only 4 days without difference in the length of the school day. A sleep log was used to ascertain time of lights off for sleep and lights on at awakening, nighttime sleep duration, and self-rated sleep quality. A visual analog scale (VAS) was also used by pupils to self-rate the level of perceived sleepiness at four specific times of the school day. Conventional statistical methods (e.g., t and chi2 tests) were used to examine differences in mean values. Sleep duration, self-rated sleepiness, and subjective sleep quality were comparable (P > .05) by gender, school schedule, school district, and parental socioeconomic status. Overall, the sleep of this sample of Parisian children around 10 years of age was rather stable in its duration and timing, suggesting flexibility to adjust to the different school schedules. PMID- 11777076 TI - Sleep-wake schedule disorder disability: a lifelong untreatable pathology of the circadian time structure. AB - Certain sleep-wake schedule disorders (SWSDs) cannot be successfully managed clinically using conventional methods of sleep therapy. We describe two cases of SWSD, the first following head trauma and the second originating during childhood, that had been misdiagnosed by physicians for many years. After conventional treatment for SWSD with light therapy and melatonin failed to bring about substantial improvement, it was determined that they were suffering from an incurable disability. Hence, we propose new medical terminology for such cases- SWSD disability. SWSD disability is an untreatable pathology of the circadian time structure. Patients suffering from SWSD disability should be encouraged to accept the fact that they suffer from a permanent disability, and that their quality of life can only be improved if they are willing to undergo rehabilitation. It is imperative that physicians recognize the medical condition of SWSD disability in their patients and bring it to the notice of the public institutions responsible for vocational and social rehabilitation. PMID- 11777077 TI - Circadian variations in the responsiveness of human gallbladder to sulfated mineral water. AB - It is well known that the intake of sulfate-containing natural mineral waters leads to contraction of the gallbladder, probably induced by the release of cholecystokinin (CCK). As early as 1959, there were some hints in the literature of circadian variations in gallbladder response; to find out whether this applies with sulfate as a stimulus, a pretest for basic information about gallbladder reaction to sulfate-containing mineral water was carried out on 19 healthy volunteers. On this basis, 15 healthy subjects of both sexes were then studied. After 6h of fasting, 500 mL of a sulfate-containing mineral water (2,800 mg SO4(2 )/L) were ingested within 5 min. The size of the gallbladder was registered ultrasonographically before and 15, 30, 60, and 120 min after drinking. The experiments were carried out seven times at different hours of the day for each volunteer. After the intake of the mineral water, the mean gallbladder size decreased significantly, followed by an increase after 60 min (P < .001). Significant circadian spontaneous variation in gallbladder size was detected (acrophase around 09:00; amplitude was 30.0% of daily average, P < .001). The contraction induced by the sulfate-containing water was most marked in the early morning hours and minimal around mid-day; the amplitude of this variation accounting for 29.0% of the daily average (P < .01). In contrast, the postdrinking relaxation was maximal around 18:00 and minimal around 9:00 (amplitude 38.5%. P < .001). These results show that the basal size of the gallbladder and its reaction to stimuli show a marked circadian variation: Whereas contractibility is maximal in the morning, dilatation is stronger in the afternoon. PMID- 11777078 TI - How to show that unicorn milk is a chronobiotic: the regression-to-the-mean statistical artifact. AB - Few chronobiologists may be aware of the regression-to-the-mean (RTM) statistical artifact, even though it may have far-reaching influences on chronobiological data. With the aid of simulated measurements of the circadian rhythm phase of body temperature and a completely bogus stimulus (unicorn milk), we explain what RTM is and provide examples relevant to chronobiology. We show how RTM may lead to erroneous conclusions regarding individual differences in phase responses to rhythm disturbances and how it may appear as though unicorn milk has phase shifting effects and can successfully treat some circadian rhythm disorders. Guidelines are provided to ensure RTM effects are minimized in chronobiological investigations. PMID- 11777079 TI - The neuroendocrine regulation of the human ovarian cycle. AB - The menstrual cycle is now thought to be mainly determined by the ovary itself, which sends various signals to the pituitary and the hypothalamus. The hypothalamus is an autonomous pacemaker, with a pulse frequency that is modulated by ovarian signals; in turn, it is indispensable to ovarian function. In women, the ovarian cycle produces a single mature oocyte each month from puberty to menopause. This follicle is rescued from atresia, the genetically controlled ovarian apoptosis (or "programmed cell death"), involving 99.9% of the follicles. Follicular growth and maturation are mostly independent of gonadotropins from the stage of primordial to antral follicles. A complete intraovarian paracrine system is implied in this gonadotropin-independent follicular growth and in the modulation of the action of gonadotropins in the ovary. Follicle-stimulating hormone (FSH) allows the rescue of a minority of follicles from atresia and is indispensable only for the final maturation of the preovulatory follicle during the follicular phase of the cycle. Luteinizing hormone (LH) is responsible for the final growth of the dominant follicle in the late follicular phase. the induction of ovulation during the LH peak, and the survival of the corpus luteum during the luteal phase. The cyclical variations of gonadotropins are under the control of ovarian steroids (estradiol and progesterone) and peptides (inhibins). The cycle length is determined by the duration of terminal follicular growth and by the fixed life span of the corpus luteum. The ovarian cycle can be monitored as well at the level of target tissues of steroids, such as the endometrium. In fact, the endometrial maturation is synchronized to follicular development, and this synchronization is indispensable for successful implantation of the embryo. The improving knowledge of follicular and endometrial physiology will allow the development of new treatments of infertility, the design of new contraceptive techniques, and a better tolerance of treatments using sex steroids. PMID- 11777080 TI - Activity rhythms of wild and laboratory golden hamsters (Mesocricetus auratus) under entrained and free-running conditions. AB - The golden hamster (Mesocricetus auratus) is one of the most frequently used laboratory animals, particularly in chronobiological studies. One reason is its very robust and predictable rhythms, although the question arises whether this is an inbreeding effect or rather is typical for the species. We compared the daily (circadian) activity rhythms of wild and laboratory golden hamsters. The laboratory hamsters were derived from our own outbred stock (Zoh:GOHA). The wild hamsters included animals captured in Syria and their descendants (F1). Experiments were performed under entrained (light: dark [LD] 14h:0h) and under free-running (constant darkness, DD) conditions. Locomotor activity was recorded using passive infrared detectors. Under entrained conditions, the animals had access to a running wheel for a certain time to induce additional activity. After 3 weeks in constant darkness, a light pulse (15 min, 100 lux) was applied at circadian time 14 (CT14). Both laboratory and wild hamsters showed well pronounced and very similar activity rhythms. Under entrained conditions, all hamsters manifested about 80% of their total 24h activity during the dark portion of the LD cycle. The robustness of the daily rhythms was also similar. However, interindividual variability was higher in wild hamsters for both measures. All animals used the running wheels almost exclusively during the dark portion of the LD cycle, although the wild hamsters were three times more active. The period length, measured in constant darkness, was significantly shorter in wild (23.93h +/- 0.10h) than in laboratory hamsters (24.06 +/- 0.07h). The light-induced phase changes were not different (about 1.5h). In summary, these results indicate that the laboratory hamster is not much different from the wild type. PMID- 11777081 TI - Circadian characteristics of corticosterone secretion in red-backed voles (Clethrionomys gapperi). AB - To provide necessary background for study of stress response in red-backed voles (Clethrionomys gapperi), the circadian and ultradian rhythm in corticosterone release was characterized. Animals were maintained under a 16h light, 8h dark cycle. A total of 55 males and 46 females provided 101 independent blood samples over a 6-month span. Samples were obtained at 1h to 2h intervals during the light and at 2h intervals during the dark. Using edited data (5 values beyond the upper 95% limit were removed), a significant time effect was found by analysis of variance (ANOVA) for both sexes at P < .001. The composite single cosine best describing the circadian wave-form for each sex consisted of three components (24h, 12h, and 6h), each significant at P < .05 (overall model P < .001). The 24h mean (mesor) was about 60% higher in females than males (646 ng/mL vs. 412 ng/mL, P = .01), with amplitudes of 429 and 298 ng/mL being proportional (66% vs. 72%) to the respective mesor. The predictable range of change within a 24h span (determined by the double amplitude of a 24h + 12h + 6h cosine model) was large: It was more than 1600 ng/mL for females and more than 900 ng/ mL for males. Highest values were found during the dark phase, with the 24h acrophase located at 2h into the dark span for both sexes. With the caveat of fewer samples obtained during dark than during light, the actual peak values for females occurred at 2h and for males at 6h into the 8h dark span. These results provide baseline information about the circadian time structure for serum corticosterone in red-backed voles under normal light-dark, low-stress conditions. PMID- 11777082 TI - Water deprivation and circadian changes in plasma arginine vasotocin and mesotocin in the domestic hen (Gallus domesticus). AB - Possible circadian variations in plasma levels of arginine vasotocin (AVT) and mesotocin (MT) were assessed in domestic hens (Gallus domesticus) under a 12h:12h light-dark (LD) schedule. Blood samples were taken at 4h intervals, and neurohypophyseal hormone levels were determined by radioimmunoassay. Marked circadian changes in both AVT and MT were observed in hens provided free access to water. Minimal and maximal AVT levels occurred at 08:00 and 20:00, respectively. Minimal MT levels occurred at 20:00, whereas maximal MT levels occurred over a broad time period of 04:00 to 12:00. In water-deprived hens, plasma AVT levels were elevated at each time point, and the circadian variations in plasma AVT and MT levels were attenuated. These results demonstrate that rhythmicity in neurohypophyseal function in a lower vertebrate species, like that in mammals, is disrupted by osmotic stress. PMID- 11777083 TI - Retinal circadian rhythms in humans. AB - Circadian rhythms in the retina may reflect intrinsic rhythms in the eye. Previous reports on circadian variability in electrophysiological human retinal measures have been scanty, and the results have been somewhat inconsistent. We studied the circadian variation of the electrooculography (EOG), electroretinography (ERG), and visual threshold (VTH) in subjects undergoing a 36h testing period. We used an ultrashort sleep-wake cycle to balance effects of sleep and light-dark across circadian cycles. Twelve healthy volunteers (10 males, 2 females; mean age 26.3 years, standard deviation [SD] 8.0 years, range 19-40 years) participated in the study. The retinal functions and oral temperature were measured every 90 min. The EOG was measured in the light, whereas the ERG and the VTH were measured in the dark. Sleep was inferred from activity detected by an Actillume monitor. The EOG peak-to-peak responses followed a circadian rhythm, with the peak occurring late in the morning (acrophase 12:22). The ERG b-wave implicit time peaked in the early morning (acrophase 06:46). No statistically significant circadian rhythms could be demonstrated in the ERG a-wave implicit time or peak-to-peak amplitude. The VTH rhythm peaked in the early morning (acrophases 07:59 for blue and 07:32 for red stimuli). All retinal rhythms showed less-consistent acrophases than the temperature and sleep rhythms. This study demonstrated several different circadian rhythms in retinal electrophysiological and psychophysical measures of healthy subjects. As the retinal rhythms had much poorer signal-to-noise ratios than the temperature rhythm, these measures cannot be recommended as circadian markers. PMID- 11777084 TI - 24h variation in the expression of the mt1 melatonin receptor subtype in coronary arteries derived from patients with coronary heart disease. AB - Previous studies presented evidence for impaired nocturnal secretion and synthesis of melatonin in patients with coronary heart disease (CHD). This study aimed to investigate whether the melatonin receptor subtype mt1 is differentially expressed in coronary arteries derived from patients with CHD (n = 9) compared to patients with dilative cardiomyopathy (CMP; n = 10) who served as controls. Expression of the mt1 receptor was studied in sections of isolated coronary arteries by a reverse transcriptase-polymerase chain reaction (RT-PCR) and a Western immunoblot technique. In addition, the data from the Western blotting of 15 patients were interpolated against the exact time of aortic clamp to study the 24h expression of the mt1 receptor. The analyses of the results from both methods indicated the presence of the mt1 receptor in all of the individuals. No statistically significant difference was observed in the receptor expression between patients with CHD and those with CMP (in arbitrary units: 3.39 +/- 3.08 versus 3.91 +/- 2.78). Expression of the melatonin receptor in the coronary arteries of the whole patient group presented a 24h variation, with the lowest values detectable after 02:00 up to the late morning hours and a progressive increase beginning after 13:00 until 00:00 (mesor = 3.66, amplitude = 3.23, acrophase = 20.45, P = .0003). When studying the 24h variation in patients with CHD and CMP separately, a nearly similar circadian course was observed. In conclusion, we demonstrated for the first time a 24h variation of a melatonin receptor subtype in human vessels. Furthermore, in relation to our results, we suggest that the expression of the mt1 melatonin receptor in the coronary arteries is probably not impaired in patients with CHD. PMID- 11777085 TI - Circadian pattern of simulated flight performance of pilots is derived from ultradian components. AB - Studies suggest some physiologic, cognitive, and behavioral 24h rhythms are generated by cyclic components that are shorter in period than circadian. The aim of this study was (1) to examine the hypothesis that 24h human performance rhythms arise from the integration of high-frequency endogenous components and (2) to quantify the contribution of each higher frequency component to the phenotype of the rhythm. We monitored the performance of 9 experienced pilots by employing an array of cognitive-based tests conducted in a flight simulator so that, over the 6-day experiment, data were obtained for each 2h interval of the 24h. The activity-rest schedule of the subjects, no matter the exact clock time schedule of sleep and activity, always consisted of 14h activity (when they carried out regular professional duties) and 10h rest, with at least 8h of sleep. The simulated combat scenarios consisted of simple and complex tasks associated with target interception, aircraft maneuvering, and target shooting and downing. The results yielded two indices: the number of prominent periodicities in the time series and the relative magnitude of the amplitude of each relative to the construction of the composite 24h waveform. Three cyclic components (8h, 12h, and 24h) composed the observed 24h performance pattern. The dominant period and acrophase (peak time) of the compound output rhythm were determined by the interplay between the amplitudes of the various individual ultradian components. Task complexity (workload) increases the expression of the ultradian entities in the 24h pattern. We constructed a model composed of the multiple ultradian components; the composite output defined a "time span" (of 2h-4h duration) as opposed to an exact "time point" of high and low performance, endowing elevated functional capability. PMID- 11777086 TI - Community rehabilitation. AB - Classifying rehabilitation services is not easy, and there is no agreed nomenclature. One way of classifying services to use the WHO ICIDH-2 model of illness. Services could specialize in one or more domains. Those services currently referred to as community rehabilitation services would be classified as services that specialized in intervening at the level of participation, and in the local aspects of physical and social context. They are an important part of a network of specialized services. PMID- 11777087 TI - Community rehabilitation in the United Kingdom. AB - OBJECTIVE: To investigate the extent and nature of community rehabilitation services within the United Kingdom. DESIGN: A postal survey starting with the Community Rehabilitation Network and extending to any other teams identified or making contact. SETTING: The National Health Service within the UK. SUBJECTS: Any team who identified themselves as a community rehabilitation service that worked 'primarily with adults with physical disability' within the UK. INTERVENTION: A questionnaire was sent to each team identified with follow-up telephone contact to clarify answers and/or to encourage replies. RESULTS: One hundred and fifty two organizations were sent questionnaires and 145 replied, but 47 were excluded for various reasons leaving 98 valid replies. Four types of team were identified: community rehabilitation teams, young disabled community teams, community teams for older adults, and specific client group teams. There were huge variations in management arrangements, team composition, goals of the services and likely lifespan of the service. CONCLUSIONS: Community rehabilitation in the UK is currently characterized by small, often short-term teams with poor identity and the term has no clear or consistent meaning. PMID- 11777088 TI - A survey of services provided by community neurorehabilitation teams in South East England. AB - OBJECTIVE: To survey the role, function and staffing of community rehabilitation teams in London and the South East NHS Region of England who work with neurologically disabled people, with emphasis on services provided for traumatic brain injury. DESIGN: Telephone survey using a structured interview with team leaders. SETTING: London and South East NHS Regions of England (population 15.6 million). SUBJECTS: Community rehabilitation teams. MAIN OUTCOME MEASURES: A structured interview about service provision. RESULTS: Thirty-five teams were found in 25 Health Authorities serving 14 million people. In a further five Health Authorities, another five teams did not participate. There were fewer than 1.5 community team professionals for 4,000-5,000 neurologically disabled. Teams had seen less than 3% of disabled traumatic brain injuries. Most focused on physical disability. Only two teams specialized in consequences of cognitive impairment or personality change. Stroke and multiple sclerosis were the most common referrals. Sixty per cent of teams had no clinical psychologist. The composition of teams is described, as is caseload, clinical role, outcome measures used, professional links, work practice and staffing issues. CONCLUSIONS: Community physical disability teams seem insufficiently resourced to provide a comprehensive service for the neurologically disabled. There are not enough teams generally, and too few specialize in psychosocial problems. All teams should include a clinical psychologist, should have specialist resources for cases from ethnic minorities and formal policies for staff security. There needs to be clarity over the range of services provided and to whom, and this linked to prevalence of disability and team resourcing. PMID- 11777089 TI - Home-based rehabilitation for people with stroke: a comparative study of six community services providing co-ordinated, multidisciplinary treatment. AB - OBJECTIVE: To describe and compare six community services providing co-ordinated, multidisciplinary rehabilitation to people with stroke. DESIGN: Prospective, descriptive, quantitative study. SETTING: England and Northern Ireland. SUBJECTS: Community rehabilitation teams and the patients treated by them. MAIN OUTCOME MEASURES: Annual numbers treated, Barthel Index, mortality, place of discharge, crude costs. RESULTS: Between mid-1997 and mid-1999, data were collected on 1076 patients who received community-based rehabilitation of whom 48.7% were male. Mean age (SD) was 71 years (13.11; 115 (10.7%) were under 55 years of age and 278 (25.9%) under 65 years of age. Median time between stroke and intervention by the community service was six weeks (25th, 75th percentiles 2.6, 14.4 weeks) and 80.5% had been admitted to hospital. The median Barthel score at the start of community rehabilitation was 15 (11.0, 18.0) and at the end was 18.0 (14.0, 20.0). Median duration of intervention was 12 weeks (6.0, 22.0). At the end of community rehabilitation 912 patients (86.5%) were in the community, 52 (4.9%) had died, 10 (0.9%) were in hospital and 77 (7.3%) in long-term care. Comparative data given here are for one year, 1998, when a total of 519 patients began community rehabilitation. Details of 1855 face-to-face interventions were also recorded from subsets of 10 consecutive patients. CONCLUSIONS: Community rehabilitation teams differed in their target populations, in the timing and duration of intervention. A taxonomy of four types of co-ordinated community based rehabilitation for people with stroke is proposed: (1) Early-supported discharge rehabilitation aimed to reduce length of hospital stay and offered an alternative to hospital rehabilitation. (2) Post-discharge rehabilitation provided additional rehabilitation and aimed for a seamless transfer of patients from hospital to community. (3) General practitioner-oriented post-stroke rehabilitation provided an alternative to hospital admission and rehabilitation. (4) Late community rehabilitation provided patients with the opportunity of an autonomous service, unconnected with hospital or GP referral. Purchasers need to decide for what purpose a team is to be set up. Researchers need to be similarly aware of diversity in community rehabilitation before comparisons are made. PMID- 11777090 TI - The need for a multidisciplinary outreach service for people with spinal cord injury living in the community. AB - OBJECTIVE: To identify the nature and extent of perceived unmet needs of people with spinal cord injury (SCI) living in the community and to determine their preferences regarding multidisciplinary outreach service delivery. DESIGN: Structured telephone interviews. SETTING: Spinal Injuries Unit, Queensland, Australia. SUBJECTS: Sixty people with SCI living in the community were approached for interview and 54 agreed to participate. RESULTS: The results reflected a high need for a specialist, multidisciplinary SCI outreach service following primary rehabilitation. There were a diversity of issues faced by people with SCI. A high or very high need was reported by 31% of participants in relation to physical changes, by 24% regarding transport, by 22% for work issues and by 19% with respect to ongoing education needs. The greatest perceived barrier to needs being met was limited local specialist knowledge about SCI (81% of participants). A service model which includes access to telephone advice was endorsed by 79% of participants, and 43% supported home visiting that is available to rural and remote areas. Spinal Injuries Unit outpatient clinic appointments were also a preference for service delivery (40% of participants). CONCLUSIONS: Trial and evaluation of the telephone as a primary medium for service delivery, and education of local service providers is recommended. PMID- 11777091 TI - A survey of physiotherapy and occupational therapy provision in UK nursing homes. AB - BACKGROUND: Nursing homes in the UK are increasingly regarded as potential rehabilitation facilities for disabled older people. OBJECTIVE: To determine the current physiotherapy and occupational therapy provision to UK nursing homes. SAMPLE: Four hundred private nursing homes in England, Scotland and Wales were selected by stratified proportional random sampling and surveyed by postal questionnaire. RESULTS: The response rate for the effective sample was 346/355 (97%). Only 10% of residents were in current receipt of physiotherapy, mostly through private physiotherapists employed by the nursing homes. Occupational therapy was being provided to only 3.3% of residents. CONCLUSION: Older people in nursing homes in the UK currently receive little physiotherapy and occupational therapy input and are particularly isolated from National Health Service (NHS) services. PMID- 11777092 TI - Clinical standards for specialist community rehabilitation services in the UK. AB - OBJECTIVE: To develop a set of clinical standards for specialist community rehabilitation services in the UK and to undertake a preliminary survey of consultants who provide those services. DESIGN AND METHODS: The proposed set of standards was adapted from the previously published standards for inpatient services, by a working party of the British Society for Rehabilitation Medicine (BSRM). Consensus was then achieved by an iterative consultation process in five rounds. A postal survey was conducted on behalf of the BSRM amongst its consultant members providing community rehabilitation services in the UK, who were asked to assess their services in relation to these standards, and to comment on the standards themselves, their usefulness and applicability. RESULTS: Fifty consultants who ran specialist community rehabilitation services agreed to participate, of whom 29 (58%) actually responded. Overall, the standards appeared to be acceptable to most, and mainly struck the right level, being attained by the majority of services. Twenty-five (89%) felt the standards were helpful and 26 (93%) felt that they covered the main aspects of specialist community rehabilitation services: 23 (79%) found them at least partially applicable to their own service. CONCLUSIONS: Proposed clinical standards have been developed for specialist community rehabilitation services in the UK. It is likely that they will require further refinement with time, and modification is required to adapt them to different subspecialities and settings. PMID- 11777093 TI - Effect of a physical therapeutic intervention for balance problems in the elderly: a single-blind, randomized, controlled multicentre trial. AB - OBJECTIVE: To establish the effect of a short, individualized exercise programme on balance dysfunction in the elderly. DESIGN: A single-blind, randomized, controlled, multicentre trial. SETTING: Physical and recreational therapy departments from two rehabilitation centres. PARTICIPANTS: Ninety-four subjects of >75 years with functional balance problems living independently or in a residential care facility. Seventy-seven subjects completed the intervention period and four-week follow-up. At a one-year follow-up 49 subjects were evaluated on balance functioning. INTERVENTIONS: Twelve sessions of an individualized balance training programme (experimental group) or 12 sessions of an individualized extra attention programme (control group) given in 4-6 weeks. MAIN OUTCOME MEASURES: Berg Balance Scale and the Dynamic Gait Index to establish balance functioning, a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression. RESULTS: Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group (p f 0.001, p f 0.001, respectively). However the effect disappeared at a one-year follow-up on the Berg Balance Scale. No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme. Results on the other response variables revealed no effect of the intervention. CONCLUSION: A short individualized exercise programme can improve functional balance in people aged 75 years and older. This improvement was maintained at least for one month but had worn off by one year. PMID- 11777094 TI - A comparison of two types of electrical stimulation of the quadriceps in the treatment of patellofemoral pain syndrome. A pilot study. AB - OBJECTIVE: To compare a commercially available electrical muscle stimulation regime with a new form of stimulation for the rehabilitation of the quadriceps in patients with patellofemoral pain syndrome. SETTING: A research facility within a teaching hospital. METHODS: Sixteen patients (four men, 12 women) with patellofemoral pain, demonstrable quadriceps atrophy, but normal gait parameters were randomly allocated to one of two treatment groups. One group received a sequential mixed frequency stimulation pattern from a standard device. The other group received a new form of stimulation from an experimental stimulation device that contained simultaneous mixed frequency components. OUTCOME MEASURES: Isometric and isokinetic extension torque, muscle fatigue rate, pain, functional questionnaire, step test, knee flexion, and quadriceps cross-sectional area. RESULTS: These showed significant improvements for both groups after treatment (p < 0.05) in all outcome measures except flexion and fatigue rates, but no significant differences between the two stimulation regimes (p > 0.05). CONCLUSION: Both stimulators performed similarly on patients with patellofemoral pain giving significant improvements for all patients for muscle strength, pain, self-reporting function and step testing. There were no significant differences between the two types of stimulation. PMID- 11777095 TI - Development and validation of the Nottingham Leisure Questionnaire (NLQ). AB - OBJECTIVES: To reduce the length of the Nottingham Leisure Questionnaire (NLQ) in order to make it more suitable for postal use, and to evaluate its test-retest reliability, sensitivity, stability and validity in relation to other measures of activities of daily living (ADL), mood and handicap. METHOD: The NLQ was shortened and the response categories collapsed. Results from a previous trial which had used the NLQ were reanalysed to establish if significant group differences were maintained. The new version of the NLQ was subsequently tested for test-retest reliability on a new group of patients from the Nottingham stroke register who were asked to complete it twice. The new NLQ and other measures were sent to patients in a multicentre rehabilitation trial (TOTAL) six and twelve months after recruitment for postal completion. SUBJECTS: One hundred and thirty seven consecutive patients from the Nottingham stroke register and 466 patients with a stroke in a multicentre rehabilitation trial. RESULTS: The original NLQ was reduced from 37 to 30 items and from five to three response categories. Data from an earlier study were reanalysed and differences between treatment groups remained. The results of a test-retest analysis using kappa showed that six items had excellent agreement, 15 good and nine fair, suggesting acceptable test-retest reliability. Results from the rehabilitation trial showed that the subjects performed all items and few additional activities were suggested. Higher NLQ scores were associated with higher subscores on the Nottingham Extended Activities of Daily Living Scale (NEADL) and lower NLQ scores with living alone and worse emotional health. CONCLUSION: The NLQ has been successfully modified for postal self-administration but there is potential for further development. PMID- 11777096 TI - Assessment of emotional problems in people with multiple sclerosis. AB - OBJECTIVE: To investigate the occurrence of emotional problems in multiple sclerosis (MS) patients. The utility of rating scales used to measure such problems was studied to make recommendations for clinical practice. DESIGN: Questionnaires were both sent by post and completed with an assistant psychologist at a home visit. SUBJECTS: Ninety-six MS patients in contact with a rehabilitation consultant. MEASURES: Patients were assessed using the Guy's Neurological Disability Scale (GNDS), Extended Activities of Daily Living Scale (EADL), Hospital Anxiety and Depression Scale (HAD), Beck Anxiety and Depression Scales (BAI, BDI), Clinical Outcomes in Routine Evaluation Measure (CORE) and the Brief Symptom Inventory (BSI). RESULTS: Rates of anxiety and depression ranged from 16% to 48% according to the measures used. All mood scales were highly significantly correlated with each other. Disability as measured by the GNDS, but not the EADL, was significantly correlated with all mood measures. Kappa values showed poor correspondence in the classification of cases. Receiver operating characteristic curves indicated an optimum cut-off point of 7/8 on the HAD and 2/3 on the General Health Questionnaire (GHQ-12). CONCLUSIONS: Rates of emotional problems were low given the highly disabled population studied. The HAD was relatively insensitive in comparison with the BAI and BDI. The GHQ-12 was sensitive and therefore recommended as a short screening measure. An alternative short screen, 'Emotional GNDS', was proposed. PMID- 11777097 TI - Risk factors for burn-out in caregivers of stroke patients, and possibilities for intervention. AB - OBJECTIVE: To identify which caregivers of stroke patients living at home experience the highest levels of strain and are at risk of burn-out, and to investigate how support for caregivers of stroke patients could best be organized, and when this support should be offered. DESIGN AND SETTING: Caregivers of stroke patients were recruited in four regions of the Netherlands. A total of 212 caregivers were interviewed. Multiple stepwise regression analysis was performed to determine the effects of patient and caregiver characteristics, resources, coping strategies and duration of the caregiver role on caregiver strain, mental well-being and vitality. SUBJECTS: The majority of the caregivers were female spouses. Their mean age was 64 years, and their socioeconomic status middle class. Stroke had occurred about 3.5 years ago on average. MAIN OUTCOME MEASURES: The following main outcome measures were used: the Caregiver Strain Index, and two scales of the Short Form-36 to measure caregivers' mental well being and vitality. RESULTS: Severe cognitive, behavioural and emotional changes in the patient constitute the main risk factors for caregiver burn-out. Women, younger caregivers and caregivers in poor physical health were also identified as risk groups. Caregivers with high perceived self-efficacy, satisfied with social support, and frequently using the coping strategy confronting, experience less strain, higher mental well-being and greater vitality. Duration of the caregiver role does not influence caregivers' strain, mental well-being or vitality. CONCLUSIONS: Women, younger caregivers, caregivers in poor physical health, and caregivers of patients with severe changes are at risk of burn-out. Support programmes should focus on self-efficacy, social support, and the coping strategy confronting. No specific moment could be identified at which support programmes should be offered. PMID- 11777098 TI - Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. AB - Community respiratory viruses (CRVs) are an important cause of morbidity and mortality among recipients of hematopoietic stem cell transplants (HSCT). At the Fred Hutchinson Cancer Research Center, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) infections in HSCT recipients have been studied intensively for more than a decade. Over time, mortality from these infections has declined as the approach to diagnosis has become more aggressive and more stringent preventive measures have been instituted. However, mortality among HSCT recipients with RSV or PIV pneumonia remains high. Uncontrolled studies at our center suggest that prompt therapy with aerosolized ribavirin has reduced mortality from RSV pneumonia but does not appear to affect the course of established PIV pneumonia. Two controlled clinical trials of ribavirin therapy for RSV infection in HSCT recipients are in progress. PMID- 11777099 TI - Preemptive treatment of pediatric bone marrow transplant patients with asymptomatic respiratory syncytial virus infection with aerosolized ribavirin. AB - Respiratory syncytial virus (RSV) is a cause of serious respiratory infections in pediatric patients. RSV infection may be especially devastating in pediatric bone marrow transplant (BMT) recipients. Because of the high mortality attributed to RSV lower respiratory tract infection, a pilot study of preemptive treatment of asymptomatic RSV shedding in pediatric BMT recipients was conducted. Nasopharyngeal wash specimens from 25 pediatric BMT recipients were screened for RSV infection prior to patients' admission to the University of Utah Pediatric Bone Marrow Transplant Unit and then on a weekly basis during the 1996 and 1997 RSV seasons. Samples from 7 asymptomatic patients tested positive for RSV, and the patients were treated with aerosolized ribavirin for 5 days; none developed clinical RSV disease. Two patients had multiple episodes asymptomatic RSV shedding. One patient required 2 courses of treatment for clearance of RSV. PMID- 11777100 TI - Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: focus on community respiratory virus infections. AB - Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant (HSCT) recipients, cosponsored by the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Society for Blood and Marrow Transplantation, were issued in October 2000. The guidelines recommend that to minimize transmission of community respiratory virus (CRV) infection, health care workers and visitors with symptoms of upper respiratory tract infection be restricted from having contact with HSCT recipients and candidates undergoing conditioning therapy. To screen HSCT recipients for CRVs, active clinical surveillance for CRV disease should be conducted on all hospitalized HSCT recipients and candidates undergoing conditioning therapy, including daily monitoring for signs and symptoms of CRV infections. Respiratory syncytial virus (RSV) is the most important CRV because it is the most prevalent and because RSV pneumonia has a high case-fatality rate. For this reason, it is recommended that respiratory secretions of any hospitalized HSCT candidate or recipient with signs and symptoms of CRV infection be tested promptly for RSV. If test results are positive, the patient should be treated early and aggressively. Early preemptive therapy with such treatments as aerosolized ribavirin has been proposed, but limited data preclude a recommendation as to the optimal strategy. Lifelong seasonal influenza vaccination is recommended for all HSCT recipients. PMID- 11777101 TI - Diagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host. AB - Infections due to community-acquired respiratory viruses are important causes of morbidity and mortality among immunocompromised patients. Respiratory syncytial virus, influenza viruses, and parainfluenza viruses are the most frequent causes of serious lower respiratory tract infections in this patient population. Early diagnosis, often possible with the use of rapid detection assays, is essential for optimal management and prevention of the spread of these serious infections to other vulnerable patients. PMID- 11777102 TI - Respiratory virus infections in stem cell transplant patients: the European experience. AB - The frequency of and survival from community-acquired respiratory virus (CRV) infections among patients undergoing allogeneic or autologous stem cell transplantation (SCT) were evaluated in a prospective study conducted at 37 medical centers affiliated with the European Group for Blood and Marrow Transplantation. Of the 40 CRV infections diagnosed in 1863 patients (739, allogeneic SCT; 1124, autologous SCT), 20 were attributed to respiratory syncytial virus (RSV), 4 to parainfluenza viruses, and 16 to influenza virus A. The overall survival rate among SCT recipients with CRV infections was 76%; 8 patients, all recipients of allogeneic transplants, died after diagnosis of CRV infection, but only 5 of these deaths (3, RSV; 2, influenza A virus) were attributable to the infection. The overall rate of death directly attributable to RSV and influenza A virus infections in allogeneic SCT recipients was 1.1%. In an 18-month extension, an additional 53 patients with CRV were identified. Results for the combined data were similar to those from the first phase of the study. PMID- 11777103 TI - Community respiratory virus infections in bone marrow transplant recipients: the M.D. Anderson Cancer Center experience. AB - Community respiratory virus (CRV) infections are common among bone marrow transplant (BMT) recipients during community outbreaks. At M.D. Anderson Cancer Center (MDACC), experience with CRV infection in this population over the past decade suggests that BMT recipients in the preengraftment phase are at special risk of progression of upper respiratory tract infection (URTI) to pneumonia. After pneumonia is established, no currently available therapy substantially reduces mortality. For BMT recipients with respiratory syncytial virus URTIs, treatment with ribavirin and intravenous immunoglobulin may be helpful in preventing progression to pneumonia and thus in reducing mortality, but this approach requires confirmation in controlled clinical trials. Prevention of CRV infection in this vulnerable patient population is crucial to reducing morbidity and mortality. Aggressive infection control precautions, which have been in effect at MDACC since 1994, have reduced nosocomial transmission of these potentially lethal infections. PMID- 11777104 TI - Testing the effectiveness of cognitive-behavioral treatment for substance abuse in a community setting: within treatment and posttreatment findings. AB - This study evaluated the short-term effectiveness of cognitive-behavioral treatment (CBT) for substance abuse delivered in a community setting. At entry into outpatient community substance abuse treatment, participants (N = 252) were randomly assigned to 3 conditions: high-standardization CBT, low-standardization CBT, and treatment as usual. Treatment consisted of 12 weekly individual therapy sessions. There was a significant decrease in substance use from baseline, with participants reporting being abstinent on 90% of within-treatment days and 85% of days during the 6 months posttreatment. However, there were no significant differences in outcomes across conditions. Findings do not support the hypothesis that disseminating CBT to community settings will improve outcomes and suggest that standard substance abuse counseling may be more effective than previously thought. PMID- 11777105 TI - Why are we here at the clinic? Parent-child (dis)agreement on referral problems at outpatient treatment entry. AB - Do clinic-referred children and their parents agree on the problems for which treatment is undertaken? The authors asked 381 outpatient-clinic-referred children and their parents to list, independently, the child's target problems. Of the parent-child pairs, 63% failed to agree on even a single problem. When problems were grouped into broad categories (e.g., delinquent, withdrawn), more than a third of the pairs still failed to agree on a single broad problem area. Parent-child agreement was higher for externalizing than for internalizing problem categories (though poor for both). Low parent-child agreement may help explain the poor outcomes often reported for clinic-based child therapy. PMID- 11777106 TI - Beyond unfavorable thinking: the illness cognition questionnaire for chronic diseases. AB - The literature on chronic diseases recognizes the role of illness cognition as a mediator between stress and illness. Few conceptualizations and instruments, however, give an indication of both unfavorable and favorable ways of adjusting to an uncontrollable long-term stressor, such as a chronic disease. The authors propose 3 generic illness cognitions that reflect different ways of reevaluating the inherently aversive character of a chronic condition: helplessness as a way of emphasizing the aversive meaning of the disease, acceptance as a way to diminish the aversive meaning, and perceived benefits as a way of adding a positive meaning to the disease. A self-report instrument, the Illness Cognition Questionnaire, was developed to assess these cognitions across different chronic diseases. The results support the reliable and valid assessment of these illness cognitions in patients with rheumatoid arthritis and multiple sclerosis and indicate the maladaptive function of helplessness and the adaptive function of acceptance and perceived benefits for the long-term physical and psychological health of patients with a chronic disease. PMID- 11777107 TI - Anxiety and depression in mothers of children undergoing bone marrow transplant: symptom prevalence and use of the Beck depression and Beck anxiety inventories as screening instruments. AB - This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview. An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least I of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder. PMID- 11777108 TI - Positive and negative life changes following sexual assault. AB - A longitudinal study was conducted to investigate (a) the timing and course of posttraumatic growth and (b) the relations between positive and negative life changes and posttraumatic distress among recent female sexual assault survivors (N = 171). Most survivors reported positive change even at 2 weeks postassault. Positive changes generally increased over time and negative changes decreased, although change in different domains followed different courses and there was significant individual variability in change patterns. Both positive and negative changes were associated with distress in expected ways, although the relations with negative changes were stronger. The least distress at 12 months was reported by those who noted positive life changes at both 2 weeks and 12 months postassault. Implications for theory and research on posttraumatic growth are discussed. PMID- 11777109 TI - Hopelessness as a mediator of the association between social support and depressive symptoms: findings of a study of men with HIV. AB - Data from a prospective longitudinal study were used to investigate whether hopelessness mediates the association between social support and depression, as hypothesized by L. Y. Abramson, G. I. Metalsky, and L. B. Alloy (1989). Measures of hopelessness, social support, and depression were administered to 103 HIV infected men and readministered 6 months later. Findings indicated that low baseline social support predicted increases in hopelessness and depression. Increases in hopelessness predicted increases in depression after controlling for baseline social support. Low baseline social support did not predict increased depression when hopelessness was controlled statistically. PMID- 11777110 TI - Dialectical behavior therapy for binge eating disorder. AB - This study evaluated the use of dialectical behavior therapy (DBT) adapted for binge eating disorder (BED). Women with BED (N = 44) were randomly assigned to group DBT or to a wait-list control condition and were administered the Eating Disorder Examination in addition to measures of weight, mood, and affect regulation at baseline and posttreatment. Treated women evidenced significant improvement on measures of binge eating and eating pathology compared with controls, and 89% of the women receiving DBT had stopped binge eating by the end of treatment. Abstinence rates were reduced to 56% at the 6-month follow-up. Overall, the findings on the measures of weight, mood, and affect regulation were not significant. These results support further research into DBT as a treatment for BED. PMID- 11777111 TI - Subtyping binge eating disorder. AB - Cluster-analytic studies of bulimia nervosa and binge eating disorder (BED) have yielded 2 subtypes (pure dietary and mixed dietary-negative affect). The authors aimed to (a) replicate the subtyping with BED, (b) consider alternative approaches to subtyping, and (c) test the stability in individual differences in the subtyping. Cluster analyses of 101 patients revealed a dietary-negative affect subtype (33%) and a pure dietary subtype (67%). The dietary-negative affect subtype was characterized by greater eating-related psychopathology and psychological disturbance. Cluster analysis produced different results from alternative subtyping approaches (by major depression or by binge eating frequency). Cluster-analytic subtyping of data at 2 time points 4 weeks apart for a subset of 73 patients demonstrated significant consistency (kappa = .55). Findings suggest that moderate dieting is characteristic of BED and that affective disturbances occur in a subset of cases that represent a more disturbed variant. The subtypes may represent reasonably stable individual differences. PMID- 11777112 TI - The evaluation of a sexual assault risk reduction program: a multisite investigation. AB - This article summarizes the results of the Ohio University Sexual Assault Risk Reduction Project, which is a program designed to reduce college women's risk for sexual assault. The program was evaluated at 2 separate universities with 762 women. Participants were randomly assigned either to the program or to the no treatment comparison group, and they completed measures that assessed sexual victimization, dating behaviors, sexual communication, and rape empathy at the pretest and at the 2-month and 6-month follow-ups. At the 2-month follow-up, there were no differences between the groups on any of the outcome measures. However, those women who were moderately victimized during the 2-month follow-up were significantly less likely to be revictimized during the 6-month follow-up period if they participated in the program. PMID- 11777113 TI - Concluding causation from correlation: comment on Burns and Spangler (2000). AB - This commentary critiques the study conducted by D. D. Burns and D. Spangler (2000) in which the relationship between homework compliance and therapy outcome was estimated using structural equation modeling (SEM). Although the authors of the commentary advocate the use of SEM, they suggest greater caution in the indiscriminate endorsement of a causal relationship based on (a) correlational data and (b) retrospective accounts of the main predictor variable within a cross sectional design. This discussion also highlights a need to address the issue of therapist competence in homework administration. The results of Burns and Spangler's report are consistent with existing empirical evidence suggesting that compliance with homework facilitates therapeutic outcome. However, the gold standard for determining causal inferences rests on prospective, experimental research rather than on retrospective, correlational models. PMID- 11777114 TI - A multidimensional meta-analysis of treatments for depression, panic, and generalized anxiety disorder: an empirical examination of the status of empirically supported therapies. AB - The authors report a meta-analysis of high-quality studies published from 1990 1998 on the efficacy of manualized psychotherapies for depression, panic disorder, and generalized anxiety disorder (GAD) that bear on the clinical utility and external validity of empirically supported therapies. The results suggest that a substantial proportion of patients with panic improve and remain improved; that treatments for depression and GAD produce impressive short-term effects: that most patients in treatment for depression and GAD do not improve and remain improved at clinically meaningful follow-up intervals: and that screening procedures used in many studies raise questions about generalizability, particularly in light of a systematic relation across studies between exclusion rates and outcome. The data suggest the importance of reporting, in both clinical trials and meta-analyses, a range of outcome indices that provide a more comprehensive, multidimensional portrait of treatment effects and their generalizability. These include exclusion rates, percent improved, percent recovered, percent who remained improved or recovered at follow-up, percent seeking additional treatment at follow-up, and data on both completer and intent to-treat samples. PMID- 11777115 TI - Deny nothing, doubt everything: a comment on Westen and Morrison (2001). AB - It is remarkable that so many important issues in psychotherapy research are touched on and, in some cases, more thoroughly explored in D. Westen and K. Morrison's (2001) meta-analysis and its discussion. Although no previously unanswered questions are resolved on the basis of their findings, original approaches to familiar questions are attempted and intriguing data are presented. Westen and Morrison's capacity to "think outside the box" while they seek to answer very familiar questions is most impressive. In the final analysis, the most significant outcome of Westen and Morrison's laudable effort can be that it might lead other psychotherapy researchers to do important things differently in the future. PMID- 11777116 TI - Issues of measurement and mechanism in meta-analyses: comment on Westen and Morrison (2001). AB - The authors suggest that D. Westen and K. Morrison's (2001) meta-analysis of treatment is critically limited in the consideration of measurement and mechanisms of therapeutic change. The measures included in the analysis fail to represent a comprehensive coverage of the domains within which change is expected. Moreover, they do not measure the theoretically derived constructs currently conceived as being central to each disorder. Further, the particular meta-analytical approach taken prohibits evaluation of the treatment components responsible for change. The authors reviewed the most recent data on comorbidity as an issue of treatment efficacy and generalizability, proffer an interpretation for the difference in outcome results across the 3 diagnostic groups, and discuss internally valid methodologies for the bridging from research to clinical practice. PMID- 11777117 TI - Determining the pertinence of psychotherapy outcome research findings for clinical practice: comment on Westen and Morrison (2001). AB - D. Westen and K. Morrison's (2001) article is a challenge to advocates of empirically supported therapies (ESTs) and to the research enterprise that has determined which therapies are given the EST designation. Their concern that the long-term effects of ESTs are understudied and, apparently, weak is valid. However, their pessimistic conclusions about the generalizability of the results from outcome studies of ESTs are based on a serious logical error. The authors of the present article described an alternative research method that can address important and appropriate questions about the generalizability of ESTs. Continued dialogue between proponents and opponents of contemporary trends in psychotherapy outcome research is encouraged. PMID- 11777118 TI - The status of empirically supported therapies: comment on Westen and Morrison's (2001) multidimensional meta-analysis. AB - In this commentary, a meta-analytic review by D. Westen and K. Morrison (2001) is put in a historical context of the controversies over the effects of psychotherapy. It is suggested that recalculations of the effects of psychotherapy have been common in past debates and that Westen and Morrison's estimates understate the effects of therapy. Data are summarized that suggest that outcomes in clinical practice are equivalent to clinical trials research, but only when patients receive similar levels of treatment and regardless of whether empirically supported therapies are offered. Treatment gains are generally maintained. It is suggested that outcomes management strategies would be far more efficient than efficacy and effectiveness research in maximizing patient outcomes. PMID- 11777119 TI - A longitudinal investigation of information processing and cognitive organization in clinical depression: stability of schematic interconnectedness. AB - This study longitudinally investigated information processing and cognitive organization in clinical depression. The main hypothesis was that individuals whose depression had remitted would show a significant cognitive shift on information processing (e.g., deactivation of negative processing) but not on cognitive organizational tasks, Forty-five individuals with clinical depression completed 2 information processing and 2 cognitive organizational tasks at initial assessment. At 6-month follow-up, the sample (23 remitted, 22 stable depressed) was readministered the tasks. As expected, information processing shifted significantly in individuals who had improved symptomatically, whereas negative cognitive organizational indices remained stable. The implications of these results are discussed as they pertain to the cognitive vulnerability, maintenance, treatment, and recurrence of depression. Directions for future research are suggested. PMID- 11777120 TI - The efficacy of problem-solving communication training alone, behavior management training alone, and their combination for parent-adolescent conflict in teenagers with ADHD and ODD. AB - Two family therapies were compared using teens with attention deficit/hyperactivity disorder. Ninety-seven families were assigned to either 18 sessions of problem-solving communication training (PSCT) alone or behavior management training (BMT) for 9 sessions followed by PSCT for 9 sessions (BMT/PSCT). Both treatments demonstrated significant improvement in ratings of parent-teen conflicts at the midpoint but did not differ. By posttreatment, both produced improvement on ratings and observations but did not differ. Significantly more families dropped out of PSCT alone than out of BMT/PSCT. At most, 23% of families showed reliable change either by midpoint or by posttreatment, with no differences between therapies. Yet 31%-70% of families were normalized. Group-level change and normalization rates support treatment efficacy, whereas indices of reliable change are less impressive. PMID- 11777121 TI - Comparative outcomes for individual cognitive-behavior therapy, supportive expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. AB - This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG). and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments. PMID- 11777122 TI - Eating problems and the observed quality of mother-daughter interactions among girls with type 1 diabetes. AB - This study examined how eating problems are linked to autonomy and intimacy in the observed interactions of 88 diabetic girls (M = 14.9 years) and their mothers. On the basis of self-reported symptoms, teens were classified as having no eating problems (n = 40), mild eating problems (n = 30), and frequent eating problems (n = 18). Mothers and daughters participated in 2 videotaped problem solving tasks (1 diabetes related and I a general parent-teen issue) that were rated with a macroanalytic coding system (Autonomy and Intimacy Rating System). Compared with interactions among mothers and daughters with no eating problems, interactions among mothers and daughters with eating problems simultaneously constrained the expression of autonomy and intimacy. Findings support clinical theory that links eating problems to emotional misattunement in the mother daughter relationship, which is postulated to interfere with the teen's capacity for individuation. PMID- 11777123 TI - The temporal relationship between emotional distress and cigarette smoking during adolescence and young adulthood. AB - Empirical evidence regarding the causal nature of the relationship between emotional distress and tobacco use in male and female adolescents provides support for both the distress-to-use and the use-to-distress hypotheses. Using a cross-lagged model with 3 waves of data from 2,961 adolescents followed into young adulthood, the authors tested the hypothesis that this relationship changes over time. As hypothesized, emotional distress in Grade 10 was associated with increased smoking in Grade 12 for both boys and girls. Smoking in Grade 12 was in turn associated with increased emotional distress in young adulthood. The addition of 3 third factors (rebelliousness, deviance, and family problems) to the model did not alter the results. Results suggest that the relationship between tobacco use and emotional distress is a dynamic one in which distress initially leads to use but then becomes exacerbated by it over time. PMID- 11777124 TI - Exposure to violence against a family member and internalizing symptoms in Colombian adolescents: the protective effects of family support. AB - Associations between exposure to serious violence against a family member and internalizing symptoms, and the protective effects of support from family versus friends, were examined in 5,775 adolescents (50% female; mean age = 15.2 years, SD = 2.0) with data from a national, random household survey of residents in Colombia, South America. After accounting for the effects of age, gender, and family life events other than violence, support from family buffered the relations between exposure to violence and adjustment; this relation was strongest for girls and younger adolescents. Disclosure to friends appeared to be protective for younger adolescents but harmful for older adolescents, and this relation was only observed for hopelessness. Results are discussed in terms of cognitive processing models of adjustment to violence. PMID- 11777125 TI - Suicide attempts among sexual-minority youths: population and measurement issues. AB - Two questions were addressed regarding suicide attempts among sexual-minority youths: Who should be classified as a sexual minority, and what constitutes a suicide attempt? Results from 2 studies indicated that sexual-minority youths, broadly defined in terms of sexual orientation and recruitment venue, were slightly more likely than heterosexual youths to report a suicide attempt. To afford a more accurate assessment of suicide attempts, a detailed measure distinguished true from false attempts. This method eliminated over half of suicide attempt reports among sexual minorities because they were false attempts ideation rather than a concrete act to end life. Furthermore, many true attempts were not life threatening, suggesting that the reports were attempts to communicate the hardships of lives or to identify with a gay community. PMID- 11777126 TI - Predicting the impact of child sexual abuse on women: the role of abuse severity, parental support, and coping strategies. AB - Female Navy recruits (N = 5,226) completed surveys assessing history of childhood sexual abuse (CSA), childhood strategies for coping with CSA, childhood parental support, and current psychological adjustment. Both CSA and parental support independently predicted later adjustment. In analyses examining whether CSA victims' functioning was associated with CSA severity (indexed by 5 variables), parental support (indexed by 3 variables), and coping (constructive, self destructive, and avoidant), the negative coping variables were the strongest predictors. A structural equation model revealed that the effect of abuse severity on later functioning was partially mediated by coping strategies. However. contrary to predictions, the model revealed that childhood parental support had little direct or indirect impact on adult adjustment. PMID- 11777127 TI - Surgeon information giving practices prior to laryngectomy: a national survey. AB - Prior to the proposed development of a pretreatment counselling package for patients with cancer of the larynx or pharynx, a study was undertaken to determine current information giving practice prior to laryngectomy. A postal questionnaire was sent to all UK ENT consultants registered in the Medical Directory. The response rate was 88%, with 48% meeting the study's entry criteria. Counselling practice varies widely. Surgeons report an average of 15 min available for discussion with the patient: 84% gave the diagnosis and discussed the treatment options at the same consultation. The size of the department, as measured by cases seen per year, did not correlate with the consultation time although it did with the numerous different issues discussed. Whilst the survey supports the need and desire for an appropriate counselling package, many surgeons feel that they alone know what the patient's information needs are. PMID- 11777128 TI - Airway fire during tracheostomy: prevention strategies for surgeons and anaesthetists. AB - Airway fires are an uncommon but real and devastating complication of tracheostomy. One such fire in a 31-year-old man is described. Surgical fires are discussed, and 15 reported cases of tracheostomy fire are reviewed. A tracheostomy protocol, adopted by our department and designed to avoid this life threatening complication, is described. Surgeons and anaesthetists involved in tracheostomy must understand the fire hazard and how to avoid it. PMID- 11777129 TI - Pre-operative electrocardiograph examination. AB - The leading cause of death following surgery is a cardiac event, and an electrocardiogram is the most common pre-operative test to investigate coronary artery disease. Fifty adults, who required an electrocardiogram, undergoing general surgical procedures, were recruited into this pilot study, which investigated the examination rate of electrocardiographs by doctors pre operatively. Each tracing was folded in one corner and a paperclip prevented full pre-operative viewing without its removal. Results suggest that 30% of ECGs were not opened and the records of 58% patients overall had no mention of the ECG having been performed. Further analysis showed no correlation with the examination rate of the electrocardiograph with patient age or fitness. If this reflects normal clinical practice, it is sub-optimal use of resources and warrants further audit. PMID- 11777130 TI - A technique to control bleeding from an inaccessible part of an aortic end-to-end anastomosis. AB - A simple technique is presented for the control of bleeding from the posterior aspect of an aortic end-to-end anastomosis. PMID- 11777131 TI - Paradoxical embolus: an unusual indication for upper limb amputation. AB - Paradoxical emboli occur when venous embolic material passes into the arterial circulation (via a right-to-left cardiac shunt). The association of paradoxical emboli and arterial ischaemia has been described previously, especially with respect to cerebral infarcts. We describe a case in which double paradoxical emboli following a long haul flight, resulted in emergency amputation of an upper limb. Amputation resulting from a paradoxical embolus has not previously been described. PMID- 11777132 TI - An observational study of 256 cases of vascular trauma in the north western province of Pakistan. AB - During the past 10 years Peshawar has dealt with increasing casualties with penetrating trauma inflicted by a wide variety of missiles. The aim of this study was to assess whether delay in arrival and mode of presentation affects the outcome of patients with penetrating vascular trauma. Prospective data were collected on 256 vascular injuries in 248 patients (median age, 29 years; range, 7-60 years) between January 1995 and June 1998. Early presentation (group A, 55 cases, < 12 h) was compared with late presentation (group B, 201 cases, > 12 h). The majority of injuries (93%) were caused by fire-arms. Arterial injuries accounted for 71% of the total, venous injuries accounted for 10% and 19% were mixed. The site of injury was the lower limb (61%), upper limb (32%), abdominal cavity (5%) and neck (2%). Patients presented with absent pulses (56%), haemorrhage (46%), false aneurysms (8%), A-V fistula (5%) and 11% presented with more than one sign. There were significantly more lower limb amputations in group A than group B (23% versus 5%; P < 0.05), with fractures having a positive association with lower limb amputations (odds ratio, 0.32; 95% CI, 0.13-0.94; P < 0.05). Group A had a higher mortality than group B (18% versus 7%; P < 0.05). This study shows that patients with vascular trauma can be managed successfully with clinical assessment alone. Patients with fractures were more likely to suffer eventually from lower limb loss. Due to self-selection, arrival at the hospital less than 12 h after sustaining vascular injury was associated with a higher mortality than those presenting after 12 h. PMID- 11777133 TI - Late presentation of traumatic diaphragmatic hernia in pregnancy. PMID- 11777135 TI - An assessment of clinical guidelines for the management of acute pancreatitis. AB - BACKGROUND: Recent guidelines have been issued for the management of acute pancreatitis. The aim of this study was to audit the management of acute pancreatitis in one district general hospital, to determine the problems and benefits associated with the implementation of such guidelines. METHODS: Data were collected over the period 1991-1995 for all patients diagnosed as having acute pancreatitis who were admitted to one district general hospital. Data regarding severity grading, determination of aetiology and treatment of mild and severe pancreatitis were analysed in conjunction with the recommendations issued by the British Society of Gastroenterology Working Party on the management of acute pancreatitis in 1995. RESULTS: A total of 210 patients were admitted on 263 occasions; 16% of cases were severe but severity prediction was inaccurate. 56.1% had gallstone pancreatitis and 20.9% had idiopathic pancreatitis. Definitive treatment of gallstones was within the recommended time limit in only 70.1%. 27 patients experienced recurrent attacks of pancreatitis before definitive treatment of their gallstones, due either to inadequate investigation for gallstones after suboptimal ultrasound examination (n = 12) or to inappropriate delay before definitive treatment of gallstones (n = 15). Recommendations for the management of severe cases with early ITU/HDU admissions and CT scanning were not followed. 28 day mortality was 6.3%, median age of those dying was 80.5 years. CONCLUSIONS: Acceptable mortality can be achieved for acute pancreatitis despite failure to implement BSG guidelines for the management of severe acute pancreatitis. Inadequate investigation and treatment of gallstone disease leads to an unacceptable incidence of recurrent acute pancreatitis. PMID- 11777134 TI - Surgical treatment of para-oesophageal hiatal hernia. AB - The development of laparoscopic antireflux surgery has stimulated interest in laparoscopic para-oesophageal hiatal hernia repair. This review of our practice over 10 years using a standard transthoracic technique was undertaken to establish the safety and effectiveness of the open technique to allow comparison. Sixty patients with para-oesophageal hiatal hernia were operated on between 1989 and 1999. There were 38 women and 22 men with a median age of 69.5 years. There were 47 elective and 13 emergency presentations. Operation consisted of a left thoracotomy, hernia reduction and crural repair. An antireflux procedure was added in selected patients. There were no deaths among the elective cases and one among the emergency cases. Median follow-up time was 19 months. There was one recurrence (1.5%). Seven patients (12%) required a single oesophagoscopy and dilatation up to 2 years postoperatively but have been asymptomatic since. Two patients (3%) developed symptomatic reflux which has been well controlled on proton-pump inhibitors. Transthoracic para-oesophageal hernia repair can be safely performed with minimal recurrence. PMID- 11777136 TI - Acute gallstone pancreatitis in childhood. AB - Acute pancreatitis is rarely considered in the diagnosis of paediatric abdominal pain and can be misdiagnosed. Gallstones are uncommon in children and are a rare cause of pancreatitis. Trauma, infections and idiopathic causes are the commonest aetiological factors. Three cases of gallstone-induced acute pancreatitis with jaundice in children are reported which resolved with conservative treatment. The gallstones were managed by laparoscopic cholecystectomy with or without endoscopic retrograde cholangiopancreatography (ERCP). The three children had presented previously to a doctor with symptoms of gallstone disease but the diagnosis was missed. It is concluded that acute pancreatitis should be considered in children presenting as an emergency with abdominal pain. Children with recurrent attacks of upper abdominal pain should be investigated for gallstone disease so that the diagnosis is made before the development of potentially serious complications such as acute pancreatitis and jaundice. PMID- 11777137 TI - The management of simple hepatic cysts: sclerotherapy or laparoscopic fenestration. AB - BACKGROUND: Prior to the era of laparoscopic surgery, open surgical deroofing was considered to be the most appropriate therapy for uncomplicated simple hepatic cysts. Recently, there have been a number of reports of successful laparoscopic fenestration of simple hepatic cysts. Simple aspiration of these cysts is associated with a high recurrence rate. Cyst sclerosis with alcohol and, more recently, minocycline hydrochloride have been found to be effective in their management. So far there have been no trials comparing laparoscopic deroofing with sclerotherapy. A lack of consensus in their management results in considerable confusion and difficulty in deciding the optimum form of therapy. METHODS: A systematic review of articles on the subject appearing in journals in the English language was conducted using the Medline database and by cross referencing. RESULTS AND CONCLUSIONS: Both laparoscopic deroofing and cyst sclerosis have been found to be effective in partial or complete obliteration of the cyst and in the relief of symptoms produced by the cyst. It is essential to rule out cystadenoma, malignancy, biliary communication and infection prior to treating these cysts. Alcohol/minocycline based sclerotherapy has the advantage of being associated with a lower incidence of complications. Surgery is indicated if it is difficult to rule out the above mentioned conditions, in the presence of biliary communication, in those cysts where sclerosis has been ineffective and in cases of recurrence. The choice between open and laparoscopic surgery depends on the location of the cysts within the liver parenchyma. PMID- 11777138 TI - Feasibility study of colonoscopy as the primary screening investigation in relatives of patients with colorectal cancer. AB - AIM: Relatives of patients with colorectal cancer are thought to be at a higher risk for this disease than the average population. We aimed to determine whether colonoscopy is a feasible primary screening investigation for this group to identify premalignant and malignant lesions. METHODS: A total of 449 people underwent colonoscopy and all had one or more relatives with colorectal cancer, of these, 212 were classified as 'asymptomatic' and 237 as being 'symptomatic'. Colonoscopy commenced at 40 years of age or 10 years younger than the youngest affected relative. RESULTS: Neoplastic change, benign and malignant, was found in 25.5% of the 'asymptomatic' group and 24% of the 'symptomatic' group; in 26% of those with one first degree relative, 39% with two or more first degree relatives and only 19% with second degree relatives. 38% of lesions were out of reach of a flexible sigmoidoscope. No known complications occurred. CONCLUSIONS: It is feasible to perform colonoscopy as the primary investigation for the first degree relatives of patients with colorectal cancer. The yield of neoplastic lesions is sufficient to make this appropriate. PMID- 11777139 TI - 'Occult' breast cancer. AB - The aim of this paper is to explore current trends in the diagnosis, investigation and treatment of patients presenting with axillary lymph node metastases without a primary in the breast being found and, more rarely, those cases with metastatic breast cancer where the primary remains unknown--the so called, 'occult' breast cancer. A retrospective study of 25 reported cases were selected from our database at the Royal Marsden and 6 patients were found to have true 'occult' breast cancer. These 6 patients are all still alive with no primary ever having been found in the breast. A literature review was then undertaken exploring the changing trends in this diagnostic enigma. MRI scanning, it is reported, may reveal the primary. Occult cancers in which imaging totally fails to show the primary will become increasingly rare. The prognosis of these, however, may be surprisingly better than one would expect from the nature of their presentation. PMID- 11777140 TI - The supratrochlear lymph nodes: their diagnostic significance in a swollen elbow joint. AB - In the differential diagnosis of a swollen elbow, the palpation of the supratrochlear glands is useful. They are not enlarged in a traumatic elbow joint. They are enlarged, discrete and shotty in rheumatoid arthritis. In tuberculosis, they are enlarged, matted and they may caseate and form a cold abscess on the medial aspect of the supratrochlear region of the arm. PMID- 11777141 TI - Pulmonary thromboendarterectomy. AB - Pulmonary thromboendarterectomy (PTE) provides a curative alternative to the otherwise fatal condition of chronic thromboembolic pulmonary hypertension (CTEPH). However, the condition is under-diagnosed due to a lack of awareness. An acceptable operative mortality of around 10% and long-term survival exceeding medical therapy or transplantation makes PTE a favourable choice for the treatment of CTEPH. Outcome is further optimised if the disease is diagnosed early and patients referred to specialised centres. An increase in the number of surgical procedures will also contribute to lower the mortality associated with this condition. PMID- 11777142 TI - Adhesive retention dressings are more comfortable than alginate dressings on split skin graft donor sites--a randomised controlled trial. AB - A prospective randomised trial examining the effectiveness, comparative comfort and ease of care of two different split skin graft donor site dressings was performed. One of the dressings was an alginate (Kaltostat), and the other an adhesive retention tape (Mefix). Alginates are the standard plastic surgical dressing, whereas the use of adhesive retention tapes as a donor site dressing presents a novel use of a readily available product. A total of 30 consecutive patients requiring split skin grafts were randomised to receive either alginate or retention donor site dressings. Dressings were assessed by interview and questionnaire at 24 h and 48 h and at 2 weeks, and by wound review at 2 weeks. Retention dressings were found to be more comfortable. They also required less nursing care and attention. The retention dressings allowed the patients easier mobility and a greater range of daily activities, especially washing. There was no significant difference in wound healing nor in complications. Adhesive retention tape applied directly to the split skin graft donor site wound is an effective, cheap and comfortable dressing requiring little postoperative care. PMID- 11777143 TI - A comparison of junior hospital doctors interpretation of acute radiographs using an X-ray box and a window. AB - A statistically significant number of clinically important features are missed when radiographs are interpreted by holding an X-ray up against the window when compared with using an X-ray box. These findings are most probably accounted for by a quantifiable difference in light intensity. PMID- 11777144 TI - Operative treatment of anal fissure. PMID- 11777145 TI - Tibial nailing using an elementary Ilizarov frame. PMID- 11777146 TI - The 'Tellytubby Tummy', a novel technique for laparostomy management. PMID- 11777147 TI - Confirming placement of distal locking screws without X-rays. PMID- 11777148 TI - Getting governance to work in surgery. PMID- 11777149 TI - Patency and life-spans of failing hemodialysis grafts in patients undergoing repeated percutaneous de-clotting. AB - We set out to determine retrospectively the primary and secondary patency rates, as well as the life-spans, of failing polytetrafluoroethylene dialysis grafts after repeated percutaneous mechanical de-clotting. The study group consisted of all patients who had undergone percutaneous mechanical de-clotting, balloon angioplasty, or angiography of theirpolytetrafluoroethylene hemodialysis grafts at our institution from 1 January through 30 April 1999. Patency of the hemodialysis grafts was calculated using Kaplan-Meier analysis. A total of 161 percutaneous de-clotting procedures were performed on 59 of 71 patients. At 1 year, the primary and secondary surgical patency rates of the grafts were 29% and 61.4%, respectively The life-spans of the polytetrafluoroethylene grafts after repeated percutaneous de-clotting and surgical interventions was 93.5% at 6 months, 78% at 1 year, 58.8% at 2 years, and 35% at 3 years. The patency rates after the 1st, 2nd, and 3rd de-clotting procedures were 55.9%, 61.9%, and 55.8% at 3 months and 32.2%, 40.8%, and 31.4% at 6 months, respectively (P=0.40). The patency rate of grafts after mechanical de-clotting using the Arrow-Trerotola thrombectomy device was not statistically different from that of the crossed angioplasty balloon technique alone (P=0.38). Further, there was no difference in the life-spans of grafts whether they were located in the upper or lower extremity Because reocclusion rates are similar following 1st, 2nd, and 3rd occlusions, regardless of the percutaneous mechanical de-clotting technique used, repeated percutaneous management should be undertaken to preserve each graft regardless of the number of previous de-clotting procedures. PMID- 11777150 TI - Suprarenal or supraceliac aortic clamping during repair of infrarenal abdominal aortic aneurysms. AB - Suprarenal or supraceliac aortic clamping during repair of infrarenal abdominal aortic aneurysms can be complicated by renal, hepatic, and intestinal ischemia. To determine whether suprarenal or supraceliac clamping increases morbidity and mortality we retrospectively reviewed our recent nonrandomized experience. Between January 1993 and December 1998, 716 patients underwent elective (n=682) or urgent (n=34) infrarenal abdominal aortic aneurysm repair. Infrarenal clamping was used in 516 (72. 1 %) and suprarenal or supraceliac clamping in 200 (279%). The suprarenal/supraceliac group had significantly more older patients (> or = 70 years of age) (65.5% vs 477%) and a higher incidence of preoperative renal insufficiency (75% vs 5.5%). Suprarenal or supraceliac clamping was used during repair of ruptured (n=25), juxtarenal (n=7), or inflammatory abdominal aortic aneurysms (n=4); during concomitant renal or visceral revascularization (n=43); in other difficult settings (n=13); or at the surgeon's discretion (n=108). The decision for such clamping was always made during surgery In treating ruptured aneurysms, suprarenal/supraceliac clamping (25/200) was used more often than infrarenal clamping (9/516) (12.5% vs 1.74%). Operative times were similar in both groups, but transfusion requirements and length of hospital stay were slightly greater in the suprarenal/supraceliac group. Perioperative mortality was 3.1% overall, but higher in the suprarenal/ supraceliac group than in the infrarenal (75% vs 1.4%). Postoperative complications developed in 26 (13%) of patients who underwent suprarenal/supraceliac clamping. Abdominal re-exploration was required in 9 other patients. We conclude that, despite associated comorbidities, elective suprarenal/supraceliac clamping during infrarenal abdominal aortic aneurysm repair is safe, facilitates repair, and does not significantly increase mortality. PMID- 11777153 TI - Cerebral perfusion through separate grafts for repair of acute aortic dissection with torn arch. AB - We have modified the technique of cerebral perfusion through anastomosed grafts for repair of acute arch dissections that require total arch replacement. We have performed this operation on a 71-year-old man with an acute type-A dissection and an arch tear between the orifices of the brachiocephalic arteries. We used 2 separate grafts for the brachiocephalic arteries and minimized brain ischemia by initiating antegrade selective cerebral perfusion after the 1st anastomosis. The patient had an excellent outcome. This method is simple and provides effective protection. Cerebral ischemic time can be kept under 30 minutes without need of a sophisticated pump setup or a multibranched graft. This affords extra time in case the surgeon encounters an unexpected lesion in the arch. PMID- 11777152 TI - Unstable angina and non-ST-segment elevation myocardial infarction: perspectives on combination therapy. AB - We reviewed recent clinical data on the management of unstable angina and non-ST segment elevation myocardial infarction. We concentrated on the use of new therapies, particularly in combination with both older agents and other new methods, in order to present health care providers with an overview of available treatment options. The clinical trials reviewed herein provide strong evidence and proof of principle that combination therapies targeting 1) platelet function (aspirin, thienopyridines, and GP IIb/IIIa antagonists), 2) the coagulation cascade (unfractionated heparin and low-molecular-weight heparin), and 3) the physical characteristics of the active lesion (percutaneous intervention) reduce the risk of death or ischemic complications after thrombotic progression of coronary atherosclerosis. PMID- 11777151 TI - Gender and cardiac arrhythmias. AB - The incidence of certain clinical arrhythmias varies between and women. Clinical and experimental observations suggest the existence of true differences in electrophysiologic properties between the sexes. We review these differences, possible mechanisms, clinical implications, and therapeutic considerations in the treatment of various arrhythmias in women. PMID- 11777154 TI - A Tribute to Frank F Alibritten, Jr. Origin of the left ventricular vent during the early years of open-heart surgery with the Gibbon heart-lung machine. PMID- 11777155 TI - Right atrial reduction for tachyarrhythmias in Ebstein's anomaly in infancy. AB - A 20-month-old girl with Ebstein's anomaly developed supraventricular paroxysmal tachycardia, which seemed to be a result of the wall tension of the giant right atrium. Right atrial resection reduced the wall tension and overall dimensions of the right atrium and finally resolved the tachycardia and ectopic electrical conduction. Six-year follow-up electrocardiograms confirmed continuing normal sinus rhythm without occurrence of supraventricular paroxysmal tachycardia or other ectopic electrical activity The follow-up echocardiograms showed the size of the right atrium to be unchanged from the time of operation. There are few data in the available literature about performing right atriotomy to resolve a tachyarrhythmia associated with Ebstein's anomaly and none, to the best of our knowledge, about performing right atrial resection for this purpose. PMID- 11777156 TI - Asymptomatic giant right atrial aneurysm. AB - A 5-year-old asymptomatic boy was found incidentally, on a chest radiograph, to have gross cardiomegaly; further evaluation by echocardiography showed a giant right atrial aneurysm. The patient underwent successful surgical reduction of the right atrium, closure of an atrial septal defect, and tricuspid valve repair These measures were taken to prevent thrombus formation in the right atrium, prevent paradoxical embolism, and lower the risk of atrial arrhythmias. The morphologic features of the resected atrial tissue showed paper-thin wall with a central aneurysm and focal endocardial fibrosis consistent with a diagnosis of idiopathic dilatation of the right atrium. PMID- 11777157 TI - Presentation of infantile aortic coarctation in an adult. AB - Rarely, the initial presentation of aortic coarctation, a congenital anomaly, occurs in adults. Surgical repair is indicated for symptomatic patients. We report the case of a 68-year-old woman who underwent successful surgical repair of the infantile (preductal) type of aortic coarctation with use of an interposition graft. PMID- 11777158 TI - Pseudo-false-positive exercise treadmill testing caused by systolic anterior motion of the anterior mitral valve leaflet. AB - Subendocardial ischemia as indicated by electrocardiography during exercise, in association with severe systolic anterior motion of the anterior mitral valve leaflet without left ventricular hypertrophy, has not been well described. We report the case of a 42-year-old man who presented with symptoms of exertional angina and 2-mm ST depression on treadmill electrocardiography but had a normal perfusion scan and coronary angiogram. Initially the negative angiographic results caused us to regard the treadmill results as false-positive. Subsequently, low-dose dobutamine echocardiography showed severe systolic anterior motion of the anterior mitral valve leaflet with a >144-mmHg left ventricular outflow tract gradient; we then recognized the original treadmill results to be pseudo-false-positive. Electrocardiographic changes in association with the above-described motion of the anterior mitral valve leaflet and increased left ventricular outflow tract gradient were verified by use of treadmill and supine bicycle stress echocardiography. PMID- 11777159 TI - Acute aortic valve regurgitation secondary to blunt chest trauma. AB - Blunt injury to the cardiac valves leads to progressive acute ventricular failure, which often requires urgent surgical management. In this case report, we describe an acute aortic valve rupture caused by air-bag inflation during an automobile accident. Laceration of an aortic valve cusp was treated successfully with urgent aortic valve replacement. A concomitant orthopedic injury was treated electively 15 days after cardiac surgery Acute aortic valve rupture is a very rare complication of blunt chest trauma. We discuss how to diagnose and manage this potentially catastrophic event. PMID- 11777160 TI - Latrogenic injury to the longthoracic nerve: an underestimated cause of morbidity after cardiac surgery. AB - After heart surgery, complications affecting the brachial plexus have been reported in 2% to 38% of cases. The long thoracic nerve is vulnerable to damage at various levels, due to its long and superficial course. This nerve supplies the serratus anterior muscle, which has an important role in the abduction and elevation of the superior limb; paralysis of the serratus anterior causes "winged scapula," a condition in which the arm cannot be lifted higher than 90 degrees from the side. Unfortunately the long thoracic nerve can be damaged by a wide variety of traumatic and nontraumatic occurrences, ranging from viral or nonviral disease to improper surgical technique, to the position of the patient during transfer to a hospital bed. Our patient, a 62-year-old man with triple-vessel disease, underwent myocardial revascularization in which right and left internal thoracic arteries and the left radial artery were grafted to the right coronary, descending anterior, and obtuse marginal arteries, respectively. Despite strong recovery and an apparently good postoperative course, the patient sued for damages due to subsequent winging of the left scapula. In this instance, the legal case has less to do with the cause of the lesion (which remains unclear) than with failure to adequately inform the patient of possible complications at the expense of the nervous system. The lesson is that each patient must receive detailed written and oral explanation of the potential benefits and all conceivable risks of a procedure. PMID- 11777161 TI - Pulmonary embolism after pacemaker implantation. AB - One day after implantation of a permanent pacemaker in an 82-year-old man, transthoracic echocardiography showed a mass in the right ventricle and a small pericardial effusion. Transesophageal echocardiography revealed a mass attached to the pacemaker lead. Subcutaneous administration of enoxaparin was begun, and the patient remained free of symptoms for the duration of his hospital stay Follow-up echocardiography performed before discharge failed to show the right ventricular mass, but a lung perfusion scan revealed multiple bilateral perfusion defects consistent with pulmonary emboli. The patient was discharged on a regimen of enoxaparin for another 30 days. Two years later, he remained asymptomatic. PMID- 11777162 TI - A simple method to prevent calcium embolization during aortic valve surgery. AB - Calcium embolization is a potential complication of aortic valve surgery Handling and debridement of calcified structures may lead to dislodgment of particles, which can fall into the left ventricular chamber With restoration of the heartbeat, these particles are ejected into the systemic circulation, with subsequent peripheral or coronary embolism. We have developed a simple and safe method to prevent this condition; in our practice, we have found this method to be very effective. PMID- 11777163 TI - Spontaneous echo contrast in left atrial appendage during sinus rhythm. PMID- 11777164 TI - Abdominal aortic occlusion: a rare complication of cardiac myxoma. PMID- 11777165 TI - Biventricular resynchronization as an unusual bridge to transplantation: acute effects. PMID- 11777166 TI - Hepatic venous anomalies complicating total cavopulmonary connection. PMID- 11777167 TI - Was Alfred Blalock's portrait altered? PMID- 11777168 TI - 100% cardiothoracic ratio. PMID- 11777169 TI - Genetic and environmental influences on separation anxiety disorder symptoms and their moderation by age and sex. AB - We estimated genetic and environmental influences on mother-rated DSM-III-R separation anxiety disorder (SAD) symptoms in 2043 3 to 18-year-old male and female twin pairs and their siblings (348 pairs) recruited from the Australian NH&MRC Twin Registry. Using DeFries and Fulker's (1985) multiple regression analysis, we found that genetic and shared environmental influences both contributed appreciably to variation in SAD symptoms (h2 = .47, SE = .07; c2 = .21, SE = .05) and were significantly moderated by both sex and age. Genetic influences were greater for girls than boys (h2 = .50 and .14, respectively), whereas shared environmental influences were greater for boys than girls (c2 = .51 and .21, respectively). Genetic influences increased with age. whereas shared environmental influences decreased with age. Shared environmental influences were greater in magnitude for twins than for nontwin siblings (c2 = .28 versus .13, respectively). Implications of these findings for theories of the cause of separation anxiety are discussed. PMID- 11777170 TI - Magnesium involvement in sleep: genetic and nutritional models. AB - Alterations of peripheral magnesium (Mg) concentration have been reported in association with several behavioral disorders and sleep organization. Blood Mg regulation is under a strong genetic control, whereas brain Mg regulation does not seem to be affected. We have studied peripheral and central levels of Mg and analyzed sleep in two lines of mice selected for low (MGL) and high (MGH) red blood cell (RBC) Mg levels. The same variables were also studied in C57BL/6J mice before and after 3 weeks of Mg deficiency. Whereas blood Mg was highly affected by the selection, brain Mg exhibited only small differences between the two lines. In contrast, Mg deficiency strongly decreased both central and peripheral Mg levels. Sleep analysis indicated that in both models the amount of paradoxical sleep was lower in mice with higher Mg levels. The amplitude of daily variation in sleep and slow-wave sleep delta power was markedly decreased in MGH line. Quantitative electroencephalogram (EEG) analysis also revealed a faster theta peak frequency in MGH mice, irrespective of behavioral states. Central Mg showed significant correlations with the amount of paradoxical sleep and sleep consolidation. However, because the direction of these correlations was not consistent, it is concluded that optimal, (physiological) rather than high or low, Mg levels are needed for normal sleep regulation. PMID- 11777171 TI - Effects of cross fostering on open-field behavior, acoustic startle, lipopolysaccharide-induced corticosterone release, and body weight in Lewis and Fischer rats. AB - Lewis (LEW/N) and Fischer (F344/N) rats differ on a myriad of behavioral and physiological endpoints, some of which have been reported to be affected by maternal experience in outbred rats and other strains. To assess whether epigenetic factors contribute to the differential behavioral responses to stress and pro-inflammatory challenges in these strains, the effects of cross fostering on open-field, acoustic startle, and glucocorticoid reactivity to lipopolysaccharide (LPS) were examined in the present experiment. In the open field test, although in-fostered female LEW/N and F344/N strains did not differ, female LEW/N rats displayed significantly greater activity than female F344/N rats in the cross-fostered condition. Differences between males of the two strains were increased by cross fostering, with the LEW/N strain displaying greater total activity. In acoustic startle, there was little strain difference between in-fostered or cross-fostered female rats. On the other hand, in-fostered male LEW/N rats had a significantly greater startle response than in-fostered male F344/N rats, an effect that was dramatically reduced by cross fostering. In fostered female LEW/N rats displayed a blunted corticosterone response relative to in-fostered female F344/N rats, an effect that was reduced by cross fostering. Conversely, although there was no strain difference between male in-fostered rats, cross-fostered male F344/N rats displayed a significantly greater corticosterone response to LPS than cross-fostered male LEW/N rats. Finally, body weight differences between in-fostered LEW/N and F344/N rats were reduced by cross fostering. Together, these data illustrate that maternal factors play a role in the behavioral and physiological responses to stress between the two strains. PMID- 11777172 TI - Phenotypic association of spontaneous ovulation and sexual receptivity in virgin females of Drosophila melanogaster mutants. AB - In Drosophila melanogaster females, mating stimulates ovulation/oviposition and switches off receptivity. To investigate the relationship between ovulation and receptivity, we searched for genetic variants in which ovulation occurs in virgins and characterized their behavioral phenotype. Among a collection of 333 P element insertion lines, we identified eight lines that showed elevated ovulation in virgins. These females show ovipositor extrusion toward courting males, which is normally observed in mated females. To express the amount of rejection behavior, we defined the extrusion index (EI) as a percentage of time that each female extruded the ovipositor within the total time of being courted. There was a positive correlation between ovulation level and EI, suggesting that the two traits are physiologically associated. Genetic analysis of the variants revealed two regions on the third chromosome responsible for the phenotype. PMID- 11777173 TI - Refractive change after dorzolamide use in patients with primary open-angle glaucoma and ocular hypertension. AB - The purpose of this study was to evaluate refractive and anterior chamber depth changes after short-term dorzolamide use in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study was prospective and non comparative and included 34 patients. Baseline refraction and anterior chamber depth were compared to the refraction and anterior chamber depth 14 days after commencing dorzolamide to determine if refraction or anterior chamber depth had been affected. Before dorzolamide use, the mean refractive error was -0.88 +/- 3.53 D (+/-SD). The mean refractive error was -0.94 +/- 3.65 D (+/-SD) two hours post-dose after 14 days of dorzolamide use, which was not significantly different (P = 0.50). The mean pre-treatment anterior chamber depth was 3.088 +/- 0.385 mm (+/-SD), which did not differ significantly from the post-treatment anterior chamber depth mean of 3.092 +/- 0.389 mm (+/-SD) (P = 0.88). The results of the study show that refraction and anterior chamber depth are not significantly altered by short-term dorzolamide use in patients with POAG and OH with no history of previous dorzolamide use. PMID- 11777174 TI - Effects of N-nitropyrazoles on ocular blood flow of rabbits and retinal function recovery of rat eyes after ischemic insults. AB - Twelve compounds of N-nitropyrazoles were studied for their effects on ocular blood flow in rabbits and retinal function recovery in rat eyes after ischemic insults. Of the twelve N-nitropyrazoles examined, nine increased choroidal blood flow while five increased retinal blood flow significantly. On the other hand, all twelve compounds increased blood flow in iris and ciliary muscle without exception. As for retinal function recovery after ischemic insult in rat eyes, eight out of the twelve compounds showed more significant facilitation than the control. The structure activity relationship of the N-nitropyrazoles to increase ocular blood flow and to facilitate retinal function recovery after ischemic insults were discussed. PMID- 11777175 TI - Effect of topical unoprostone on circulation of human optic nerve head and retina. AB - The purpose of the present study was to study the effect of topical unoprostone on the circulation of human optic nerve head (ONH) and retina in normal subjects. Using laser-speckle tissue blood flow analysis, normalized blur (NB), a quantitative index of tissue blood velocity, was measured every 0.125 sec at a temporal ONH site, free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). For baseline comparison (Day 0), recordings of bilateral NB(ONH) and intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were recorded in healthy volunteers before, and 45, 90, 180, and 270 min after instillation of one drop of unoprostone vehicle. On Day 1 (the day after baseline measurements), and twice daily for 7 days, one drop of 0.12% unoprostone was instilled into one eye and its vehicle into the other in a double-blinded manner. Measurements as on Day 0 were recorded on Days 1 and 7. CDI measurements were performed before and at 45 and 180 min after morning instillation on Days 1 and 7. During baseline recordings, there were no significant changes in any parameters. After administration of topical unoprostone, IOP was significantly lower bilaterally with more reduction in the unoprostone-treated eyes on Day 7. On Day 7, the NB(ONH) of the unoprostone treated eyes was significantly higher 45 min after instillation than baseline (P = 0.035 with Bonferroni's correction). Analysis of variance for repeated measurements also revealed significant difference between Day 0 and Day 7 (P = 0.0017). BP, PR, NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased, at least temporarily, following instillation of unoprostone twice daily for 7 days. Although the clinical implication of the increase is unclear, the effects of topical unoprostone on human ONH circulation deserve further consideration. PMID- 11777176 TI - Ocular and orbital blood flow velocity in patients with peripheral vascular disease and diabetes treated with intravenous prostaglandin E1. AB - The purpose of this study was to evaluate the effect of intravenous prostaglandin E1 (PGE1) on the flow velocity of the ophthalmic artery and the central retinal artery in patients with peripheral vascular disease manifested by intermittent claudication. The flow velocity of these vessels is frequently decreased in vascular patients. Since these patients were already being treated with PGE1 for their intermittent claudication, the authors wanted to evaluate the effect on the flow velocity of the ocular vessels as well. A randomized 21-week study of two groups of vascular patients was performed. The first group had intermittent claudication. The second group had intermittent claudication and were also diabetics. Both groups were treated with intravenous PGE1 for their intermittent claudication. Using the color Doppler, the flow velocities of the ophthalmic artery and central retinal artery were measured before and after the intravenous treatment. Before treatment, the flow velocity of the ophthalmic artery and the central retinal artery was decreased when compared to that in the normals. After treatment, there was a significant increase in the systolic and diastolic phases of the flow velocity in both arteries. The systolic flow velocity increased by as much as 40%, and the diastolic flow velocity increased by as much as 80%. The flow velocities of the ophthalmic artery and the central retinal artery are frequently decreased in certain ocular diseases, and this decreased flow may contribute to the ocular pathology. If intravenous PGE1 is able to increase the flow velocity of these vessels in patients with peripheral vascular disease, it is possible that it is also able to increase the flow velocity of these vessels in patients with ocular disease as well. Intravenous PGE1 may prove to be a useful adjunct therapy in eyes when ischemia is part of the pathology. PMID- 11777177 TI - Ocular and retrobulbar blood flow in ocular hypertensives treated with topical timolol, betaxolol and carteolol. AB - The purpose of this study was to evaluate the effect of topical timolol 0.5%, betaxolol 0.5% and carteolol 2% on the blood flow velocity of the central retinal artery (CRA), the posterior ciliary artery (PCA) and the ophthalmic artery (OA) in patients with ocular hypertension. A group of 14 patients with ocular hypertension and a group of 11 normals were studied. The color Doppler was used to measure the peak systolic flow velocity (PSFV) and the end diastolic flow velocity (EDFV) of the CRA, the PCA and the OA in the normals and in the patients. The normals were under no treatment, while the patients were studied before and after treatment with topical timolol 0.5%, betaxolol 0.5% and carteolol 2%. In the systolic phase, there was a significant increase in the flow velocity of the CRA with all three drugs. In the diastolic phase of the CRA, the increase was significant for timolol 0.5% and carteolol 2% but not for betaxolol 0.5%. The flow velocity of the PCA and OA remained unchanged. In this study of 14 patients with ocular hypertension, topical timolol 0.5%, betaxolol 0.5% and carteolol 2% led to a significant increase in the flow velocity of the CRA without creating a steal or decrease in the flow velocity of the PCA. PMID- 11777178 TI - In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres. AB - Solvent evaporation technique with O/O (oil/oil) emulsion was used to prepare 5 FU (5-fluorouracil) biodegradable microspheres with a polymer of poly(dl-lactide co-glycolide) combining lecithin as an emulsifier. In vitro drug release was conducted in phosphate buffer with pH 7.4 at 37 degrees C. For in vivo studies, 10 mg of 5-FU microspheres (containing 1 mg of 5-FU) were implanted in the conjunctival area of the rabbit eye. Rabbits were sacrificed at certain time intervals within 7 days after drug application. Samples of aqueous humor and sclera were prepared and analyzed by the high performance liquid chromatography (HPLC) method. The tested 5-FU microsphere contained 10% drug with a mean particle size of 4.4 +/- 0.6 microm. The microsphere had a burst release initially (64.9 +/- 1.5%), followed by a sustained release; the cumulative release at time points of 1, 10 and 21 days were 71.9 +/- 1.9%, 80.1 +/- 2.1% and 89.8 +/- 2.3%, respectively. For in vivo studies, aqueous humor levels showed a peak at the first sampling point (2 hr), then maintained low levels of 5-FU with a range 0.2-1 microg/mL. Scleral levels were 20-80 microg/mL during a 7-day study. Our results indicate that the prepared 5-FU microsphere provided a long term release for more than 1 week. The preparation showed no irritation and low toxicity (< 100 microg/mL). For application to the eye, it might be potentially useful as a complement drug system in glaucoma filtration surgery. PMID- 11777179 TI - Ocular bioavailability of ciprofloxacin in sustained release formulations. AB - A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments. PMID- 11777180 TI - Drug delivery to the posterior segment of the eye: some insights on the penetration pathways after subconjunctival injection. AB - The aim of this study is to gain an understanding of the penetration pathways for a drug to enter the posterior segment of the eye after subconjunctival injection. 14C-mannitol was injected subconjunctivally, and 14C-mannitol and 14C-inulin were injected intracamerally. The aqueous and vitreous levels were determined at selected time points. The results of subconjunctival injection and intracameral injection were compared. The vitreous level of the dosed eye is much higher than that of the corresponding contralateral eye after subconjunctival injection so that the recirculation pathway is not a dominant penetration pathway. In addition, the results also showed that it is unlikely for significant amounts of drug to move from the aqueous to the vitreous chamber after subconjunctival injection. Therefore, direct penetration is the dominant pathway for a subconjunctivally injected compound to enter the vitreous chamber. PMID- 11777181 TI - Biochemical and ultrastructural studies in the neural retina and retinal pigment epithelium of STZ-diabetic rats: effect of captopril. AB - We measured the activities of total Na+, K+-ATPase (Na, K-ATPase), its alpha1 and alpha2/alpha3 isoforms and the angiotensin-converting enzyme (ACE) in the microvascular and neural compartments of the retina, and/or retinal pigment epithelium (RPE) of streptozotocin (STZ)-diabetic rats. The effect of captopril, an ACE inhibitor on Na, K-ATPase activities was also determined and correlated to morphological changes. Insulin-dependent diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Long-Evans rats. ACE activity was inhibited by captopril (10 mg/kg given in the drinking water) for 1 month. Na, K-ATPase activity was measured spectrophotometrically or by a radioassay (32P-labeled ATP). The activity of ACE was determined by a radioassay using tritiated benzoyl-gly-gly-gly as substrate. Both the alpha1 and alpha2/alpha3 isoforms of Na, K-ATPase were present in the microvascular and neural compartments of retinas, whereas only one isoform, the alpha2/alpha3, was found in the RPE. In 2-month diabetic rats, the activity of the alpha2/alpha3 isoform was reduced in both the microvascular and neural compartments of retinas, while the activity of the alpha1 isoform was reduced only in the neural isolates. ACE activity was significantly decreased in the retinal neural compartment and unaltered in the microvascular compartment from 2-month diabetic rats. In 5-month diabetic rats, Na, K-ATPase activity was moderately but not significantly reduced in RPE preparations. Ultrastructural studies revealed a significant deepening of basal infoldings in the RPE and a noticeable increase in the size of the extracellular space between the basal infoldings of 5-month diabetic animals. Captopril stimulated Na, K-ATPase activity in the neural retina, but not in the RPE. Diabetes-induced morphological changes in the RPE were not improved by captopril. An enlargement of intercellular space between the RPE cells was a frequent finding in the treated group. In conclusion, captopril stimulated Na, K ATPase activity in the neural retina of diabetic rats. This stimulation seems to be beneficial to the neural retina. ACE inhibition, however, did not improve RPE morphological changes. Although the clinical significance of increased intercellular spacing between RPE cells in treated animals is not clearly established, we speculate that it might contribute to an increased alteration of their barrier function. Additional studies are necessary to assess both the desirable and adverse effects of captopril and other ACE inhibitors in the retinas of diabetic patients. PMID- 11777182 TI - Inhibition of lens epithelial cell growth by induction of apoptosis: potential for prevention of posterior capsule opacification. AB - As a model of the cell proliferation occurring in posterior capsule opacification (PCO), lens epithelial cells (LEC) from human and rabbit capsulotomies, and a rabbit LEC line (N/N1003A) were grown in Dulbecco's Minimal Essential Media (MEM) with 10% fetal calf serum. LEC were exposed to the calcium ionophore, calcimycin, and viability was assessed by trypan blue staining, growth by 3H-thymidine incorporation and apoptosis by annexin/propidium iodide staining, calcein AM/ethidium bromide staining and DNA laddering. Human capsulotomy samples were similarly exposed to calcimycin, and apoptosis assayed by calcein AM/ethidium bromide staining. Calcimycin exposure induced apoptosis in both rabbit LEC cultures and human LEC, and changes leading to apoptosis could be detected within 30 minutes of calcimycin treatment. The decrease in viability and growth in human and rabbit LEC was dose-dependent. These data support the further evaluation of apoptosis induction as a possible treatment mechanism to prevent development of PCO following primary cataract surgery in humans. PMID- 11777183 TI - Patient satisfaction scales: a third dimension to the assessment of the care of advanced cancer patients. PMID- 11777184 TI - Morphine in cancer pain management: a practical guide. AB - Morphine is the most practical and versatile analgesic for the relief of severe pain associated with advanced cancer. Information is available in the literature about its use in routine clinical practice. Morphine induces analgesia by reducing neurotransmitter release presynaptically and hyperpolarizing dorsal horn neurons at the postsynaptic level, thus preventing rostral transmission of nociception. Morphine has a unique metabolism via glucuronidation (UGT2B7), which results in an active metabolite (morphine-6-glucuronide). The pharmacokinetics of morphine relate to its hydrophilic characteristic, volume of distribution, route of administration and clearance. Renal failure alters its pharmacokinetics more than cirrhosis. The age of the patient and multiple medications will alter morphine pharmacokinetics. Morphine can be given by several different routes: oral, rectal, subcutaneous (s.c.), intravenous (i.v.), epidural and intrathecal. Recent experience confirms benefits of topical morphine for cutaneous pain associated with benign or malignant ulcers. Guidelines for morphine administration are reviewed, and in particular those of the Harry R. Horvitz Center for Palliative Medicine are outlined. PMID- 11777185 TI - Supportive and palliative care: experience at the Institut Jules Bordet. AB - The Supportive and Palliative Care Unit of the Institut Jules Bordet officially started its activities in February 1999. Our Unit comprises eight beds (four rooms with one bed each and two rooms with two beds each). We admit advanced cancer patients presenting with severe symptoms whose control is going to require all the expertise of a multidisciplinary team. Whilst these eight beds are identified geographically in the hospital, the team's mobility assures continuity of care for patients who wish to stay in another department. The infrastructure of the Unit and its rooms allow close family members who wish to sleep close to the patients to do so. Otherwise, visits are allowed round the clock, though always with due consideration for patients' comfort. Patients are referred either by a physician working in our Institution (medical oncologist, surgeon, or radiotherapist) or by their family physicians. Less frequently, patients themselves specifically ask to be admitted to our Unit. The activity of the Unit itself during its first year of functioning can be summarized as follows. We admitted 155 advanced cancer patients, for a total number of 210 hospitalizations. Patients were admitted a median of 35 months after their diagnosis and a median of 20 days before death. Stays were generally short (median 11 days). We systematically used quantitative assessment tools (MMSQ, MDAS,EFAT and various VAS) to detect and monitor their symptoms and any complications. The main symptoms on admission were pain, anorexia, asthenia, dyspnea and anxiety/depression. Pain, nausea/vomiting, constipation and cough were controlled in almost all patients, whereas control of asthenia and anorexia was most often insufficient. In 51% of our cases the patients could be discharged home; 40% died in the unit; 4% were transferred to long-term palliative care units and 1% to other units within our Institution (4% were still hospitalized at the time of this analysis). PMID- 11777186 TI - Oral complications in the head and neck radiation patient. Introduction and scope of the problem. AB - Head and neck cancer arises in the upper aerodigestive tract, most commonly in the oral cavity, pharynx, and larynx. The anatomy and physiology of this region are uniquely complex, and the function and appearance are critical to patients' self-image and quality of life. Head and neck cancer is related to tobacco and alcohol exposure, and is hence found more frequently in males in lower socio economic classes. These patients therefore tend to be less health conscious and to have less social support than most other groups of cancer patients. Most head and neck cancer patients are treated with high-dose radiotherapy to large irradiation fields encompassing sensitive structures, including the oral cavity and surrounding structures. Significant side effects occur in both the acute and the chronic phase, and dealing with these is a complex issue. Increasing intensity of treatment has improved survival but has also increased treatment side effects. A dedicated multidisciplinary team of oncologist, head and neck surgeon, dentist, nurse, dietician, physical therapist, social worker and in some instances plastic surgeon, prosthodontist, and psychologist is needed to provide the optimal supportive care for these patients. New developments in radiotherapy techniques are expected to lead to even higher cure rates and fewer side effects in patients with head and neck cancer. PMID- 11777187 TI - Management of oral disease prior to radiation therapy. AB - Radiation therapy for malignant tumors of the head and neck is associated with significant side effects involving the oral cavity. For example, radiation therapy leads to reduced vascularity and oxygen tension of the oral hard and soft tissues and also to salivary gland dysfunction. These changes increase the risk of dental decay and oral infections and lead to reduced healing capacity following oral surgery procedures. A severe complication of radiation therapy is osteoradionecrosis of the jaw bone. The purpose of this paper is to review preradiation oral examination and treatment. Patient management regarding oral disease prior to radiation therapy has to accomplish a number of goals: (1) to identify existing oral disease and potential risk of oral disease, (2) to remove infectious dental/oral foci before the start of radiation therapy, (3) to prepare the patient for the expected side effects with information about them, (4) to establish an adequate standard of oral hygiene to meet the increased challenge, (5) to provide a plan for maintaining oral hygiene and fluoride treatment, for oral rehabilitation, and for follow-up and (6) to inform the patient about the availability of any financial support for dental treatment, and finally (7) to establish the necessary multidiciplinary collaboration within the health care system so that oral symptoms and sequelae before, during and after the radiation therapy can be reduced or alleviated. The methods used to accomplish these goals may vary between cancer centers. Each center should have a multidisciplinary team to handle such problems. After the end of radiation therapy most of the dental treatments in our patients are done by private dentists, except for some oral surgery procedures, which are performed in hospital. In our experience, the major challenge in this process is related to (1) informing of the patient, (2) timing the coordination between all the health care workers involved, (3) establishing an adequate schedule for dental treatment and follow-up, and (4) securing patient compliance to prevent or reduce the oral side effects. PMID- 11777188 TI - Satisfaction with rehydration therapy for terminally ill cancer patients: concept construction, scale development, and identification of contributing factors. AB - Comprehensive assessment is important in determination of the efficacy of rehydration therapy for terminally ill cancer patients. To validate a multidimensional satisfaction scale, a multicenter cross-sectional study was performed. The participants were requested to complete a questionnaire on their satisfaction levels with rehydration therapy, and the primary physician recorded each patient's background. A total of 173 patients were included in this study. After the development phase, the initial instrument was shortened to a 12-item scale. In the validation phase, an exploratory factor analysis revealed underlying three subscales: satisfaction with "information giving," "disturbance of daily activities," and "treatment effect." This factor structure was ascertained by a confirmatory factor analysis. The overall Cronbach's alpha coefficient was 0.73, and those for subscales ranged from 0.73 to 0.83. The total score was significantly correlated with global satisfaction score (rho=0.53), and the "treatment effect" subscale score was moderately correlated with self perceived improvement of dehydration symptoms (rho=0.25-0.33). The test-retest examination showed fair reproductive reliability (intraclass correlation = 0.78 for total and 0.63-0.78 for subscale scores). Multivariate analyses identified that disclosure of the incurability, 15 min or more daily contact with physicians, presence of a primary responsible nurse, absence of cachexia, and absence of fluid retention symptoms were significantly associated with higher patient satisfaction. In conclusion, this scale had acceptable psychometric properties for measurement of patient satisfaction with rehydration therapy. PMID- 11777189 TI - Does awareness of diagnosis make any difference to quality of life? Determinants of emotional functioning in a group of cancer patients in Turkey. AB - The object of this study was to investigate how the information status with regard to diagnosis, in addition to social and clinical factors, influenced emotional functioning and quality of life in a group of cancer patients in Turkey. A consecutive sample of 100 cancer patients being treated for different diagnoses in a tertiary care centre were prospectively evaluated. Data on patient disease and social characteristics, clinical factors, and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were analysed by logistic regression models. A significant proportion (44%) of the patients did not know of their diagnosis of cancer. The scores on functional and symptom scales and global health status/quality of life according to QLQ-C30 did not differ according to the information given or not given on diagnosis. However, the independently significant determinants of good emotional functioning were male gender (P=0.002), low serum alanine transferase levels (P=0.025), good social functioning (P=0.002), and the absence of constipation (P=0.005). In Turkey, it is still common for cancer patients not to be informed of their diagnosis, and there is a great need to improve this situation. Honest disclosure of the truth does not worsen any dimension of quality of life in general or emotional functioning in particular. On the contrary, those with hepatic dysfunction, female gender, poor social functioning and constipation are the ones at increased risk of poor emotional functioning, and these patients may benefit from psychological screening. PMID- 11777190 TI - Physical compatibility and in vivo evaluation of drug mixtures for subcutaneous infusion to cancer patients in palliative care. AB - The objectives of this study were first to investigate the compatibility and physical stability of drug admixtures destined for s.c. administration through elastomeric infusion pumps to terminally ill cancer patients followed up at home by staff of the Palliative Care Unit (AECC), "La Paz" Hospital, Madrid and secondly, to evaluate the local side-effects related to the infusion of some of the drug mixtures to a population of 50 patients. The drug mixtures prepared included combinations of two, three, four and five of the following drugs: morphine hydrochloride, 60 mg/day; midazolam hydrochloride, 15 mg/day; haloperidol lactate, 7.5 mg/day; hyoscine-N-butyl-bromide, 60 mg/day; dexamethasone sodium phosphate, 16 mg/day; metoclopramide hydrochloride, 40 mg/day, and tramadol, 400 mg/day. Out of 86 mixtures evaluated in vitro, 52 were found to be physically compatible. Precipitation was always obtained when dexamethasone sodium phosphate at the concentrations assayed was combined with haloperidol lactate and/or midazolam hydrochloride. However, no precipitation occurred when morphine hydrochloride, the opioid most frequently used in patients of this type, and dexamethasone sodium phosphate were combined. Of the drug mixtures that were physically compatible, 18 were administered to the patient population evaluated. Very good symptom control was obtained with all of them, and especially with the mixture of morphine + midazolam + haloperidol + hyoscine, which is the one most frequently administered to cancer patients for palliative care in the final stages of life in our Unit. PMID- 11777191 TI - Does megestrol acetate down-regulate interleukin-6 in patients with cancer associated anorexia and weight loss? A North Central Cancer Treatment Group investigation. AB - Megestrol acetate improves appetite and abrogates weight loss in some patients with advanced cancer. Moreover, preliminary studies suggest that progestational agents down-regulate interleukin-6 (IL-6), an inflammatory cytokine widely implicated in cancer-associated anorexia and weight loss. The present investigation examined the effects of megestrol acetate on IL-6 in an attempt to confirm these earlier, preliminary studies. The translational component of a large multi-institutional trial, this investigation examined 85 patients with advanced cancer and weight loss. Patients had been randomly assigned to receive megestrol acetate liquid suspension 800 mg/day + placebo tablets, or oral dronabinol tablets 2.5 mg b.i.d. + liquid placebo, or both agents. Other testing included serial physician-reported weight and patient-reported appetite and global quality of life. We found no significant differences in 1-month changes in serum IL-6 according to whether patients had been treated with megestrol acetate, dronabinol, or the combination: the mean differences +/- standard deviation were 1.52+/-4.7 pg/ml, -0.62+/-3.5 pg/ml, and -0.2+/-3.1 pg/ml, respectively (P=0.40, by one-way ANOVA). Among the patients who noted alterations in their appetite over 1 month, we observed no significant changes in IL-6. Finally, changes in serum IL-6 were not associated with shifts in weight or global quality of life. Our investigation provides no evidence that megestrol acetate down-regulates IL-6 in patients with cancer-associated anorexia and weight loss. PMID- 11777192 TI - Cost-benefit assessment of inferior vena cava filter placement in advanced cancer patients. AB - We retrospectively collected data recorded between 1994 and 2000, with the aim of evaluating the cost and benefits of IVCFP (inferior vena cava filter placement) in advanced cancer patients treated in our institution alone from the radio diagnosis department's point of view. A total of 30 procedures were performed. The benefits were represented by the efficacy and the safety of the filter. The costing procedure consisted in multiplying the value of the unit index by the number of relative complexity indices. Eighty percent (24/30) of the patients were dead at the time of the study. Twenty percent (6/30) of the patients died before even being discharged from hospital. Three of them died from renal failure, owing to complete renal vein thrombosis (n=2) or hydronephrosis (n=1), and 1 from pulmonary embolism because it was exceptionally severe; the other 2 patients were cachectic, i.e., in poor general condition. The individual cost of the procedures represented only 2% of the mean entire cost of hospitalization. Seventy-six percent, 56% and 40% of the patients, were still alive at 1 month; 3 months and 6 months, respectively, with an improved quality of survival in at least 53% of the patients. The low complication rate and the low cost relative to the mean cost of hospitalization (2%) are factors in favor of using IVCFP if it is medically indicated. PMID- 11777193 TI - Supportive Care in Cancer--15 years thereafter. PMID- 11777194 TI - Relapsed, poor-prognosis ovarian cancer, individualized, interdisciplinary treatment approach, and quality of life: a case report. AB - Metastatic ovarian cancer after cisplatin-containing first-line therapy is a disease with poor prognosis. The second-line treatment options currently available can induce objective remissions, but only rarely lead to prolonged periods of response. Thus, the best possible quality of life is the main goal for these patients. We report on the course of disease in a 51-year-old woman who presented with metastatic ovarian cancer that had relapsed to the liver, cisplatin-induced renal impairment, and bone marrow tuberculosis. Because of the severe co-morbidities and the poor prognosis with a life expectancy of less than 6 months, the patient had been rejected by two other hospitals. In presenting this case, we want to demonstrate that despite poor prognostic factors, co existing morbidity, and serious therapy-related side-effects, it is possible to induce long-lasting remissions leading to sustained quality of life and ultimately to prolong the remaining life-span in selected patients. To reach such a positive outcome, it is necessary to tailor an interdisciplinary treatment approach to each patient's needs. Such treatment approaches are available in dedicated tumor centers. PMID- 11777195 TI - Validation using sensitivity and target transform factor analyses of neural network models for classifying bacteria from mass spectra. AB - Temperature constrained cascade correlation networks (TCCCNs) are computational neural networks that configure their own architecture, train rapidly, and give reproducible prediction results. TCCCN classification models were built using the Latin-partition method for five classes of pathogenic bacteria. Neural networks are problematic in that the relationships among the inputs (i.e., mass spectra) and the outputs (i.e., the bacterial identities) are not apparent. In this study, neural network models were constructed that successfully classified the targeted bacteria and the classification model was validated using sensitivity and target transformation factor analysis (TTFA). Without validation of the classification model, it is impossible to ascertain whether the bacteria are classified by peaks in the mass spectrum that have no causal relationships with the bacteria, but instead randomly correlate with the bacterial classes. Multiple single output network models did not offer any benefits when compared to single network models that had multiple outputs. A multiple output TCCCN model achieved classification accuracies of 96 +/- 2% and exhibited improved performance over multiple single output TCCCN models. Chemical ionization mass spectra were obtained from in situ thermal hydrolysis methylation of freeze-dried bacteria. Mass spectral peaks that pertain to the neural network classification model of the pathogenic bacterial classes were obtained by sensitivity analysis. A significant number of mass spectral peaks that had high sensitivity corresponded to known biomarkers, which is the first time that the significant peaks used by a neural network model to classify mass spectra have been divulged. Furthermore, TTFA furnishes a useful visual target as to which peaks in the mass spectrum correlate with the bacterial identities. PMID- 11777196 TI - Development of generic liquid chromatography-mass spectrometry methods using experimental design. AB - Standard approaches to development of liquid chromatography-mass spectrometry (LC MS) methods, either ion-pairing or reversed-phase liquid chromatography, have been through trial and error or intentional variation of experimental factors. These approaches to method optimization fail to take into account interactions between experimental factors and therefore the results may not be optimal for the combination of experimental factors. Another approach to optimization is through the use of chemometrics. Chemometric approaches can be more efficient than trial and error or intentional variation because chemometrics make use of multivariate designs; experimental factors are varied simultaneously at the various levels. Therefore chemometrics can take into account interactions between factors. The goal of this study was to develop a generic ion-pair LC-MS method for the analysis of acidic compounds using a chemometric approach called design of experiments (DOE). Four acidic compounds which cover three classes of acidic functional groups: 1-naphthyl phosphate (1), 1-naphthalenesulfonic acid (2), 2 naphthalenesulfonic acid (3), and (1-naphthoxy)acetic acid (4) were used as model compounds to develop the generic method. This study illustrates that LC-MS conditions can be optimized efficiently with minimal amount of experimentation using a chemometric approach to experimental design. PMID- 11777198 TI - Use of cumulative distribution functions to characterize mass spectra of intact proteins. AB - The MH+ ions of matrix assisted laser desorption ionization time-of-flight (MALDI TOF) spectra for a series of closely related but otherwise indistinguishable proteins were analyzed for singularity using a distribution free statistic, the Kolmogorov-Smirnov non-parametric statistic, K-S. The approach allows spectra which might otherwise be taken as identical, to be distinguished. Such analysis of the spectra may lead to a greater understanding of the chemistry of the proteins under investigation. The analysis requires only standard instrumentation. A standard data analysis protocol was developed and applied to generate a normalized cumulative distribution function (NCDF) for each spectrum. Differences in the NCDF for two different spectra were calculated and the maximum difference, deltamax compared to critical values of K-S. Values of deltamax exceeding the critical value of K-S are taken as the basis for rejecting the statistical null-hypothesis and assigning statistical significance to the differences in the two spectra. We have shown that this approach allows spectra of 1:1 mixtures of closely related recombinant proteins to be distinguished from either protein alone, and that mixtures of a 45 kDa protein and a labeled version of that protein can be distinguished from the pure material and from one another at the level of about 25%. In addition, we are able to use this approach to characterize the extent to which a synthetic glyococonjugation reaction has proceeded under circumstances of differing reaction times. PMID- 11777197 TI - Scoring methods in MALDI peptide mass fingerprinting: ChemScore, and the ChemApplex program. AB - No universally accepted score is currently available to determine when a matrix assisted laser desorption ionization (MALDI) peptide mass fingerprint (PMF) experiment has been successfully carried out. We describe a software program (ChemApplex) based on a calculated parameter (Combined Protein Score) that takes into account (1) peak intensity, (2) the mass accuracy of the match, and (3) ChemScore, a theoretical intensity factor that estimates the probability of observing a particular peptide based on a combination of chemical considerations, in particular the amino acid composition of the peptide and the amino acid sequence of the amino acids that span the cleavage site. When these three factors are taken into account both at the level of individual peptides and at the protein level, protein components in mixtures whose peptides contribute less than 1% of the total intensity can often be correctly identified, as is demonstrated for mixtures of standard proteins. Moreover, it is possible to make robust database identifications that are nearly independent of the number of masses submitted and the mass error threshold used for matching. Protein scoring based on Combined Protein Score is orthogonal to many of the commonly used probability based scoring schemes, and makes it possible to archive a more complete set of parameters that more thoroughly characterize the validity of the database match, which increases the confidence in the identifications. PMID- 11777199 TI - Investigation of the influence of charge derivatization on the fragmentation of multiply protonated peptides. AB - The fragmentation of the multiply charged peptides b-chain of bovine insulin and glucagon have been investigated under low energy collision induced dissociation (CID) conditions using an electrospray ion trap mass spectrometer. The influence of charge state, specific amino acids such as aspartate or proline, the location of basic sites, and the derivatization on the fragmentation behavior has been the focus of interest. As a basis for understanding the fragmentation process, the concept of the mobile proton was applied. A set of different derivatives was used to manipulate the sites of protonation of the peptides in order to control and improve the fragmentation behavior. These results can be applied for de novo sequencing, although the sequence-specific fragmentation processes have significant influence on the dissociation behavior of the peptides. PMID- 11777200 TI - Tandem mass spectrometry of protein-protein complexes: cytochrome c-cytochrome b5. AB - An improved method to interpret triple quadrupole MS/MS experiments of complexes of large ions is presented and applied to a study of the complex formed by the proteins cytochrome c and cytochrome b5. Modeling of the activation and dissociation process shows that most of the reaction occurs near the collision cell exit where ions have the highest internal energies. Experiments at different collision cell pressures or with different collision gases (Ne, Ar, Kr) are interpreted with a previously proposed collision model (Chen et al., Rapid Commun. Mass Spectrom. 1998, 12, 1003-1010) to calculate the internal energy added to ions to cause dissociation. Small but systematic differences under different experimental conditions are attributed to different times available for reaction. A method to correct for this is presented. Ne, Ar, and Kr are found to have similar energy transfer efficiencies. Complexes of cytochrome c and cytochrome b5 are detected in ESI mass spectra but with abundances less than expected from the solution equilibrium. Dissociation of the cytochrome c cytochrome b5 complexes with charge k gives as the most abundant fragments, cytochrome b5(+3) and cytochrome c+(k-3). Adding charges to the complex destabilizes it. A series of cytochrome c variants with Lys residues thought to be involved in solution binding replaced by Ala showed no differences in the energy required to induce dissociation of the gas phase complex. The implications for the binding of the gas phase ions are inconclusive. PMID- 11777201 TI - The proton affinity of proline analogs using the kinetic method with full entropy analysis. AB - The proton affinity of proline analogs, L-azetidine-2-carboxylic acid (Aze), L proline (Pro), and L-pipecolic acid (Pip), have been measured using the Armentrout modification of the extended kinetic method in a quadrupole ion trap instrument. Experimental values of 223.0 +/- 1.5, 224.9 +/- 1.6, and 225.6 +/- 1.6 kcal/mol have been determined for the 298K proton affinities of Aze, Pro, and Pip respectively. High level theoretical calculations using both MP2 and B3LYP methods at a variety of basis sets were carried out in order to give theoretical predictions for the 298 K proton affinity and gas phase basicity of all three analogs. Recommended values for the gas phase basicity and proton affinity for proline based on our work and other recent determinations are 216 +/- 2 and 224 +/- 2 kcal/mol. PMID- 11777202 TI - Radiochemical detection for packed capillary liquid chromatography-mass spectrometry. AB - For the identification of trace level organic molecules, such as drug or pesticide metabolites, there is need of a practical method to do packed capillary liquid chromatography-mass spectrometry (LC-MS) with radiochemical detection. This problem has been successfully solved by use of a post column flow-splitter, with coaxially transported makeup flow that increases the split flow rate to a flow compatible with commercially available radiochemical flow cells. To test the device, 14C-labeled azoxystrobin, a commercial fungicide, was analyzed by liquid chromatography-radiochemical activity monitor-mass spectrometry (LC-RAM-MS) using a 0.32 mm i.d. packed capillary column. Azoxystrobin could be detected at 500 pCi with good signal/noise. The method is general and can be used with capillary LC columns of smaller diameters. Column efficiency of about 20,000 theoretical plates/m was achieved using either radiochemical or mass spectrometric data, thus demonstrating the lack of band broadening using the described method for radiochemical detection. The simple hardware described allows the routine use of packed capillary LC with radiochemical detection. PMID- 11777203 TI - Comparing similar spectra: from similarity index to spectral contrast angle. AB - We investigated a spectral-contrast-angle (theta) method to determine whether mass spectra of structural isomers are the same or significantly different. This method represents collisionally activated dissociation (CAD) spectra as vectors in space. Mass spectra of different isomers are represented as different vectors, having characteristic lengths and direction. The derived spectral contrast angle, which is a measure of the angle between two vectors corresponding to two closely related spectra, is a measure of whether the mass spectra are the same or significantly different. We compare this method with the similarity index (SI) method and show that the spectral contrast angle method is superior and can differentiate between very similar spectra in cases where the SI cannot. Both methods can be implemented simply in situations where the analyst is called on to decide, on the basis of mass or product-ion spectra, whether reference and unknown compounds are the same or to evaluate the reproducibility of spectra comprised of many peaks. PMID- 11777204 TI - CEPH family 1362 STR database: an online resource for characterization of PCR products using electrospray ionization mass spectrometry. AB - An online database has been established in order to validate electrospray ionization mass spectrometry (ESI-MS) for genotyping and to publicize the procedures developed in our laboratory for the characterization of PCR products by ESI-MS. Genotypes derived from short tandem repeat (STR) loci that were obtained using ESI Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) have been posted for fifteen members of the CEPH family 1362 pedigree. The website provides specific information such as PCR parameters, PCR product cleanup approaches, and ESI solution compositions to enable other laboratories to reproduce our data. Links are provided to related websites in an effort to integrate information regarding the CEPH family, STR genotyping, and mass spectrometry. The database, currently available at http://www.people.vcu.edu/ dcmuddim/genotype/ will be routinely updated with genotypes from additional STR loci including PCR parameters as well as PCR cleanup strategies as further developments are completed. PMID- 11777205 TI - Comparison of the collision-induced dissociation of duplex DNA at different collision regimes: evidence for a multistep dissociation mechanism. AB - The dissociation mechanism of duplex DNA has been investigated in detail by collision-induced dissociation experiments at different collision regimes. MS/MS experiments were performed either in a quadrupole collision cell (hybrid quadrupole-TOF instrument) or in a quadrupole ion trap with different activation times and energies. In addition to the noncovalent dissociation of the duplex into the single strands, other covalent bond fragmentation channels were observed. Neutral base loss from the duplex is favored by slow activation. In fast activation conditions, however, the major reaction channel is the noncovalent dissociation into single strands, which is highly entropy-favored. Fast activation regimes can favor the entropy-driven noncovalent dissociation, while in slow heating conditions the competition with enthalpy-driven covalent fragmentation can completely hinder the dissociation of the complex. We also evidence that the noncovalent dissociation of DNA duplex is a multistep process involving a progressive unzipping, preferentially at terminal positions. This is proposed to be a general feature for complexes containing a high number of contributing interactions organized at the interface of the ligands. The overall (observed) dissociation kinetics of noncovalent complexes can therefore depend on a complicated mechanism for which a single transition state description of the kinetics is too simplistic. PMID- 11777206 TI - Mass measurement errors caused by 'local" frequency perturbations in FTICR mass spectrometry. AB - One of the key qualities of mass spectrometric measurements for biomolecules is the mass measurement accuracy (MMA) obtained. FTICR presently provides the highest MMA over a broad m/z range. However, due to space charge effects, the achievable MMA crucially depends on the number of ions trapped in the ICR cell for a measurement. Thus, beyond some point, as the effective sensitivity and dynamic range of a measurement increase, MMA tends to decrease. While analyzing deviations from the commonly used calibration law in FTICR we have found systematic errors which are not accounted for by a "global" space charge correction approach. The analysis of these errors and their dependence on charge population and post-excite radius have led us to conclude that each ion cloud experiences a different interaction with other ion clouds. We propose a novel calibration function which is shown to provide an improvement in MMA for all the spectra studied. PMID- 11777207 TI - Immune responses and immunity in hepatitis C virus infection. PMID- 11777208 TI - Intracytoplasmic localization of cathepsin D reflects the invasive potential of gastric carcinoma. AB - BACKGROUND: The present study was undertaken to investigate the role of cathepsin D in the invasiveness of human gastric cancer. METHODS: Immunohistochemical cathepsin D staining was performed in samples from 29 early gastric adenocarcinomas (papillary or tubular adenocarcinoma) and 15 gastric adenomas, and their adjacent nonneoplastic gastric mucosa. We classified the patterns of cathepsin D immunostaining into four types; type A, fine granular staining in the apical portion: type B, intense coarse granular staining in the apical portion; type C, fine granular staining in the basal portion; and type D, diffuse granular staining throughout the cytoplasm. RESULTS: All of the nonneoplastic mucosa showed an apical cytoplasmic distribution pattern (type A or type B). However, 20% (2/10) of low-grade gastric adenomas and 60% (3/5) of high-grade gastric adenomas showed an abnormal staining pattern. i.e., types C and D. Moreover, 82% (9/11) definite intramucosal gastric adenocarcinomas, and the majority of gastric adenocarcinomas with submucosal invasion [83% (15/18) of those in the mucosal part and 100% (14/ 14) of those in the invasive submucosal part] showed an abnormal staining pattern (types C and D). Interestingly, most of the carcinoma cells invading the stroma and lymphatics showed the type D staining pattern. CONCLUSIONS: These results indicate that an abnormal cytoplasmic staining pattern of cathepsin D may reflect the invasive potential of gastric carcinoma cells. PMID- 11777209 TI - Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study. AB - BACKGROUND: Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age. sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. METHODS: From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. RESULTS: Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10-3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI., 1.01-2.53; P = 0.043). CONCLUSIONS: H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer. PMID- 11777210 TI - Paired tumor marker of soluble E-selectin and its ligand sialyl Lewis A in colorectal cancer. AB - BACKGROUND: Better diagnosis of metastatic disease has been pursued by oncologists: however, many of the tumor markers have been still controversial. Our purpose was to estimate the usefulness of soluble E-selectin and its ligand sialyl Lewis A for more accurate diagnosis as a combined tumor marker for metastases in colorectal cancer. METHODS: E-selectin and sialyl Lewis A, collected from preoperative blood, were measured of its levels in 54 patients with colorectal cancer classified according to Dukes' stage. E-selectin was assayed by enzyme-linked immunosorbent assay, whereas sialyl Lewis A was quantified by enzyme immunoassay using immunoclone kit. RESULTS: The elevation in the level of E-selectin was significantly higher in Dukes' D group than that of healthy volunteers (P < 0.001, Fisher's procedure of least significance test), Dukes' A (P = 0.01), B (P = 0.025) and C (P < 0.01). Significantly higher level of sialyl Lewis A was shown in the group of metastases than that of non metastases (P < 0.0068. Student's t-test). Paired elevation of E-selectin and sialyl Lewis A was significantly higher in the hematogenous metastases than non metastases (P < 0.001, Fisher exact test). CONCLUSIONS: These results suggest that E-selectin could play some role in the progress of hematogenous metastases. The elevation of E-selectin alone or both E-selectin and sialyl Lewis A may be one of the useful indexes for more precise diagnosis of hematogenous metastases of human colorectal cancer. PMID- 11777211 TI - Clinical significance of p53 antigen and anti-p53 antibodies in the sera of hepatocellular carcinoma patients. AB - BACKGROUND: To analyze the clinical significance of serum p53 protein and anti p53 antibodies as serological markers for hepatocellular carcinoma (HCC). METHODS: We studied clinical data, i.e., age, sex, etiology, serum alpha fetoprotein (AFP) level. TMN staging, and Okuda staging in 141 patients with HCC. The sera of these patients were analyzed for serum p53 protein and serum anti-p53 antibodies by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum p53 antigen and serum anti-p53 antibodies were detected in the sera of 32 of the 141 (22.7%) patients and 26 of the 141 patients (18.4%), respectively. Of note, the HCC patients who were positive for p53 antigen (32/141) had no circulating anti p53 antibodies. When both these groups of patients were combined as a serum p53 status-positive group, the total number in this group was 58 (41.1 %). Positive status of p53 was not associated with age (P = 0.206), serum alpha-fetoprotein level (P = 0.851). Okuda staging (P = 0.243), or survival (P = 0.078), but was correlated significantly with TMN staging (P = 0.049). Interestingly, a shorter survival time (mean, 3.9 months) was noted in the serum p53 status-positive group. in comparison with the longer survival time (mean, 6.5 months) in the serum p53 status-negative group. CONCLUSIONS: Combination of the detection of serum p53 antigen and antibodies by ELISA may represent a suitable noninvasive investigation in assessing the clinical implications and prognoses of patients with HCC. PMID- 11777212 TI - Cholangiographic findings of early-stage extrahepatic bile duct carcinoma. AB - BACKGROUND: To clarify the cholangiographic findings of early-stage (T1, tumor confined to the mucosal or fibromuscular layer) extrahepatic bile duct carcinoma. METHODS: Cholangiographic images were retrospectively analyzed without other information in 55 patients with extrahepatic bile duct carcinoma who underwent surgical treatment. Tumor stages were T1 (n = 10). T2 (n = 17), and T3 (n = 28). Cholangiographic findings were classified as "diffuse sclerosis," "stenosis," "papillary polypoid filling defect," or "nodular polypoid filling defect". "Papillary polypoid filling defect" was the term used when the width of the base was smaller than the width of the polypoid filling defect. RESULTS: T1 patients showed papillary polypoid filling defects (n = 8) or nodular polypoid filling defects (n = 2) on cholangiography. When cholangiography showed papillary polypoid filling defects, 8 of the 14 resected patients showed T1 stage tumor histologically. CONCLUSIONS: In this study, 57% (8/14) of resected patients with papillary polypoid filling defects showed T1 stage tumor. No T1 stage tumor showed stenosis or diffuse sclerosis. PMID- 11777213 TI - Combined hepatocellular carcinoma and cholangiocarcinoma growing into the common bile duct. AB - We report a patient with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) growing into the common bile duct (CBD) and showing obstructive jaundice within 2 years of the onset of the disease. The patient was a 59-year-old Japanese man in whom, at the age of 57 years. a hepatic tumor was discovered by diagnostic imaging during follow-up of hepatitis B surface antigen (HBsAg) positive liver cirrhosis. The tumor was diagnosed as HCC. Epirubicin was injected twice, intraarterially. The patient then received oral etoposide therapy for the next 14 months. The treatment was initially effective, but approximately 2 years after the hepatic tumor was discovered, local recurrence of the tumor and a tumor thrombus in the CBD were discovered. Although he was treated with percutaneous transhepatic biliary drainage (PTBD), to reduce obstructive jaundice, the jaundice was irreversible and he died of severe hepatic failure. The autopsy findings confirmed that the hepatic tumor was HCC-CC, in which the HCC and CC components expressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19 9), respectively, which accurately reflected the disease process. The underlying mechanism of the growth of HCC-CC into the CBD may differ from the underlying mechanism of the development of icteric-type HCC. PMID- 11777214 TI - Pancreatic cancer complicated by disseminated intravascular coagulation associated with production of tissue factor. AB - A 54-year-old man was diagnosed as having pancreatic cancer and disseminated intravascular coagulation. His plasma tissue factor level on the 11th hospital day was 996 pg/ml (normal range, 120-270 pg/ml). He was treated with gabexate mesilate, antithrombin III, and low-molecular-weight heparin. However, he died of multiple organ failure on the 17th hospital day. The histological finding was poorly differentiated ductal adenocarcinoma of the pancreas, and the production of tissue factor in this lesion was revealed. Tissue factor is a factor that initiates blood coagulation; thus, its expression in pancreatic cancer is one of the causes of coagulation abnormalities in this disease. Although one report has demonstrated immunoreactivity for tissue factor in pancreatic cancer, the patient's detailed clinical course was not mentioned in that report. This is the first report to prove that pancreatic cancer produced tissue factor in a patient with disseminated intravascular coagulation. PMID- 11777215 TI - Insulin-like growth factor II-producing intra-abdominal hemangiopericytoma associated with hypoglycemia. AB - We report a patient with insulin-like growth factor (IGF)-II-producing hemangiopericytoma with hypoglycemia in whom repeated intra-abdominal recurrences developed over a period of about 10 years and tumor resection was performed four times. A 67-year-old woman was admitted to our hospital in 1995 because of hypoglycemic attacks. In 1985, partial resection of the small bowel had been performed for a 17-cm abdominal tumor of the transverse mesocolon, and the pathological diagnosis was hemangiopericytoma. In 1991, left hemicolectomy had been performed for a mesosigmoidal tumor associated with hypoglycemia. In 1994, hysterectomy, bilateral adnexectomy, and resection of an intrapelvic tumor were performed. The fourth operation was performed in 1996, about 10 years after the first operation. The spleen was removed, together with more than 1500 tumors having a total weight of 1,660 g. The hypoglycemia was ameliorated after each operation. Before this operation, her serum IGF-I level was low, but her IGF-II level was within the normal range; however, the Western immunoblot method showed that most of the IGF-II was high-molecular-weight IGF-II. The tissue IGF-I level was also low, and the IGF-II level was high, suggesting an IGF-II-producing tumor. We suspect that the mechanism of the hypoglycemia in this patient was related to the high-molecular-weight IGF-II produced by the tumor. The patient died in 1997 because of tumor recurrence. PMID- 11777216 TI - Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation. AB - A 52-year-old woman was found to have a liver tumor during treatment for a liver abscess. The tumor was diagnosed as intrahepatic cholangiocarcinoma by closer examinations, including a percutaneous needle biopsy. Ten years previously, she had undergone excision of a choledochal cyst, with reconstruction by Roux-en-Y hepaticojejunostomy, as treatment for Todani's type Ia congenital biliary dilation, which had been confined only to the extrahepatic bile duct. The significant association between congenital biliary dilation and hepatobiliary malignancies is well known. Some patients have been reported to develop biliary cancer long after the excision of the entire extrahepatic bile duct and hepaticoenterostomy. However, in these patients, the development mostly took place in the remnant choledochal cyst, the anastomotic site, or in the dilated intrahepatic bile duct of Todani's type IV-A congenital biliary dilation. The development of intrahepatic cholangiocarcinoma after operation has not been reported previously in a patient with Todani's type I congenital biliary dilation. This case suggests that the entire biliary tree may have a high risk of field cancerization, even in extrahepatic congenital biliary dilation. PMID- 11777217 TI - Mesalazine for ulcerative colitis complicated with diabetic nephropathy. PMID- 11777218 TI - P53 in sera for the early detection of hepatocellular carcinoma. PMID- 11777219 TI - Reappraisal of cholangiography for bile duct carcinomas: differentiation between early and advanced carcinomas. PMID- 11777220 TI - Is imaging at intermediate doses necessary during dobutamine stress magnetic resonance imaging? AB - To determine if visualization of left ventricular contraction throughout the course of a pharmacologic stress test performed with magnetic resonance imaging (MRI) (rather than solely at baseline and peak stress) is necessary, we retrospectively reviewed dobutamine MRI results in 469 consecutively referred patients for diagnosis of inducible ischemia. At each stage of pharmacologic stress, six image planes of the heart were viewed and left ventricular wall motion was scored as normal, hypokinetic, akinetic, or dyskinetic. Inducible ischemia was identified in 102 patients; in 39 patients (38%), evidence of ischemia occurred before receiving high doses of dobutamine. During testing, 103 patients developed chest discomfort consistent with angina, but only 26 of the 103 patients (25%) developed new wall motion abnormalities indicative of ischemia. Continuous image acquisition and review during dobutamine MRI pharmacologic stress testing provides a mechanism to detect ischemia and avoid premature test termination during the early stages of the procedure. Compared with protocols that image only at baseline and at peak stress, continuous acquisition and review may enhance the safety and improve the diagnostic accuracy of pharmacologic stress testing during dobutamine MRI. PMID- 11777222 TI - Can we use vertical bore magnetic resonance scanners for murine cardiovascular phenotype characterization? Influence of upright body position on left ventricular hemodynamics in mice. AB - High resolution magnetic resonance (MR) imaging is uniquely suited for cardiovascular phenotype characterization in transgenic mice. Experimental MR scanners with the high magnetic field strength are commonly built with a vertical bore design. The hemodynamic consequences of a prolonged upright body position in anesthetized mice are, however, unknown. Thus, the purpose of this work was to investigate the influence of a vertical body position on murine systemic blood pressure and left ventricular (LV) hemodynamics over time. We studied six C57Bl/6 mice at 14-16 weeks of age (body weight, 24-28 g) under isoflurane anesthesia. Positioned supine on a 37 degrees C warming pad, a microtip catheter was advanced via the right carotid artery into the left ventricle. Continuous registration of LV hemodynamics was performed at rest and after tilting of the table to a 90 degree vertical position. After tilting, there was a transient decrease of LV systolic pressure to 96% of initial values immediately after tilting with return to baseline level within 6 min. Tilting to vertical position had no influence on LV end-diastolic pressure, heart rate, maximal rate of left ventricular pressure increase, and maximal rate of left ventricular pressure decrease. Over a follow up period of 60 min in vertical position, there were no significant changes in murine hemodynamics. An acute change of body position is fully compensated by a normal orthostatic response in anesthetized mice. Prolonged upright body position exerts no significant changes in murine LV hemodynamics. Hence, high resolution MR studies for cardiovascular phenotype characterization in transgenic mice performed on vertical bore MR scanners allow measurements under physiologic conditions. PMID- 11777221 TI - Improved cine cardiovascular magnetic resonance using Clariscan (NC100150 injection). AB - We evaluated the use of Clariscan 0.75, 2, and 5 mg Fe/kg body weight in six patients to determine optimal dosing for short repetition time cine imaging. Breathhold cine images were acquired in the vertical and horizontal long axes and the short axis. Blood-pool signal-to-noise ratio increased significantly in all planes (p < 0.01) but was least marked in the short axis. Myocardial signal-to noise ratio increased by a lesser amount (p < 0.05). Myocardial to blood-pool signal-difference-to-noise ratio improved significantly in the long axes (p < 0.05) and was greatest at 2 mg Fe/kg body weight, but changes in the short axis were minor. With the 5-mg Fe/kg body weight dose, the response was reduced or reversed due to T2* effects. Visual assessment improved in all planes (p < 0.05) and was optimal at 2 mg Fe/kg body weight. In conclusion, Clariscan improves short repetition time cardiac breathhold cine imaging, particularly in the long axis planes, with an optimal dose of 2 mg Fe/kg body weight. PMID- 11777223 TI - Prosthetic heart valves and annuloplasty rings: assessment of magnetic field interactions, heating, and artifacts at 1.5 Tesla. AB - The purpose of this study was to determine the magnetic resonance (MR) safety aspects and artifacts for three different heart valve prostheses and two different annuloplasty rings that have not been evaluated previously in association with the 1.5-T MR environment. Ex vivo testing was performed using previously described techniques for the evaluation of magnetic field interactions (deflection angle and torque), heating (gel-filled phantom and fluoroptic thermometry; 15 min of MR imaging at a whole body-averaged specific absorption rate of 1.2 W/kg), and artifacts (using T1-weighted, spin echo, and gradient echo pulse sequences). One heart valve prosthesis and one annuloplasty ring showed no magnetic field interactions. Two heart valve prostheses and one annuloplasty ring displayed relatively minor magnetic field interactions (i.e., deflection angle < or = 6 degrees, torque, +1). Heating was < or = 0.7 degrees C for the five different implants. Artifacts varied depending on the amount and type of metal used to make the implants. For the three heart valve prostheses and two annuloplasty rings, the lack of substantial magnetic field interactions and relatively minor hearing indicated that MR procedures may be conducted safetly in patients with these implants using MR systems operating with static magneticfields of 1.5 T or less. Notably, these findings essentially apply to 54 different heart valve prostheses and 37 different annuloplasty rings (i.e., based on the various models and sizes available for these implants). PMID- 11777224 TI - Unveiling extracellular inorganic phosphate signals from blood in human cardiac 31P NMR spectra. AB - 31P NMR spectra of the human heart are usually contaminated by signals that originate from blood. The main blood signals are 2,3-diphosphoglycerate (2,3 DPG), which overlap and sometimes obscure the signal of myocardial inorganic phosphate used to calculate intracellular pH and to monitor metabolic changes in the heart. In this work we demonstrate, first, that even without proton decoupling the resolution of such spectra can be high enough to evaluate intracellular inorganic phosphate of myocardium in about 70% of the spectra and, second, that extracellular inorganic phosphate from blood contributes a signal in the chemical shift region of the 2-phosphate signal of 2,3-DPG. PMID- 11777225 TI - Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden. AB - Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002; 264 vs. 18 mm2, p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired. PMID- 11777226 TI - Myocardial fiber orientation mapping using reduced encoding diffusion tensor imaging. AB - A precise knowledge of the myocardial fiber architecture is essential to accurately understand and interpret cardiac electrical and mechanical functions. Diffusion tensor imaging has been used to noninvasively and quantitatively characterize myocardial fiber orientations. However, because the approach necessitates diffusion to be measured in multiple encoding directions and frequently at multiple weighting levels, the required data set size may present a limitation on its acquisition time efficiency. Applying the principles of reduced encoding imaging (REI), four basic reconstruction schemes, keyhole using direct substitution, keyhole with baseline correction, symmetrically encoded REI with generalized-series reconstruction (RIGR), and asymmetrically encoded RIGR, are evaluated in terms of their accuracy in diffusion tensorfiber orientation mapping of excised myocardial samples. Results show that the performances of all REI schemes, at approximately 50% reduced encoding, are at least comparable with that of a control experiment consisting of proportionally reduced number of full k space images. Moreover, although performances of the symmetrically and asymmetrically encoded RIGR schemes are similar, both methods provide significant improvements over the control experiment and the direct-substitution keyhole technique. These findings demonstrate the potential of the general REI methodology for diffusion tensor imaging and pave the way for modified schemes involving rapid imaging sequences or alternative k-space sampling strategies to achieve even better data acquisition time efficiency and performance. PMID- 11777227 TI - Mechanisms of the effects of nicorandil in the isolated rat heart during ischemia and reperfusion: a 31P-nuclear magnetic resonance study. AB - Nicorandil (SG75) is a potent K+-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K+-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandil-containing (100, 300, or 1000 microM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10(-3) M), nicorandil reduced ATP depletion during ischemia by 26% compared with untreated hearts. Blockade of K+ channels by glibenclamide prevented this protective effect. At all doses (10(-4) to 10(-3) M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 +/- 0.03 vs. 6.02 +/- 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K+ channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 microM). Thus, we conclude that the effects of nicorandil are caused by the simultaneous action of both mechanisms K+-channel activation and NO release. The activation of K+ channels prevents deterioration of ATP during ischemia, whereas NO release and increased coronary flow reduce the accumulation of protons--and thus the decrease in pH--during ischemia. PMID- 11777228 TI - Anomalous coronary arteries: anatomic and functional assessment by coronary and perfusion cardiovascular magnetic resonance in three sisters. AB - Combined coronary and perfusion cardiovascular magnetic resonance was performed in three sisters with angina and suspected anomalous coronary arteries. Two sisters had anomalous coronary arteries passing between the aorta and right ventricular outflow tract and had abnormal myocardial perfusion. One sister had normal anatomy and perfusion. The combined approach identified the anatomy and functional significance of suspected anomalous coronary arteries. PMID- 11777229 TI - I think I'm dumb? PMID- 11777230 TI - Correlation of heel pain with body mass index and other characteristics of heel pain. AB - A prospective, descriptive study was performed at Oakwood Healthcare medical clinics to determine the body mass index (BMI) of patients with heel pain and of a control group of patients presenting for other reasons. A questionnaire was used to obtain information in each of the patient groups and to determine characteristics of patients with plantar fascial heel pain. Standard weightbearing lateral radiographs were taken to determine overall foot structure. The typical patient was female, had heel pain for just over 1 year, with a sedentary to moderate activity level. Although height was comparable, patients with heel pain had a higher BMI (30.4 +/- 0.7) than those without heel pain (28.2 +/- 0.7, p = .04). The BMI appears to play a greater role in heel pain than does foot structure, as the authors found no structural commonalities that would explain these patients' pain. Control patients also reported a higher level of activity. Fifty-one percent exercised three or more times per week for more than 20 minutes each time, while less than half that (25.4%) of heel pain patients did so. While half of the heel pain patients had been treated by other providers prior to visiting our clinic, fewer than 25% of these patients had been instructed to lose weight by a physician. The authors feel that a BMI of 25 (the target for decreased cardiovascular risk) represents a reasonable goal for weight loss that may reduce heel pain. PMID- 11777231 TI - Articular geometry of the medial tarsometatarsal joint in the foot: comparison of metatarsus primus adductus and metatarsus primus rectus. AB - The three-dimensional surface geometry of the medial tarsometatarsal joint ("first metatarsocuneiform") of the first ray was analyzed to determine if the shape of the joint is distinct in the medially deviated first metatarsal with metatarsus primus adductus (MPA). Clinical evaluation of 29 cadaver feet identified 13 feet with MPA and 16 with metatarsus primus rectus (MPR). Three dimensional (3D) coordinates x, y, z of the first metatarsal and medial cuneiform joint facets of the feet were digitized on a Coordinate Measuring Machine (accuracy = 0.01 mm) and the data fitted with B-spline surfaces from which 3D curvature maps were generated. Comparison of means of surface-averaged maximum and minimum principal curvatures and root-mean-square curvatures showed significant (p < .0005) differences between the MPA and MPR subsets, male and female subsets, and metatarsal and cuneiform subsets. These results show that the articular shape of the medial tarsometatarsal joint in feet with MPA is significantly less contoured, or is flatter, than the same joint in normal or MPR feet. Results also showed that the female joints are more curved than male joints, and that metatarsal and cuneiform facets closely conform in shape to each other. These preliminary results may be related to questions concerning the anatomical and functional basis for the first metatarsal deviation, for radiographic presentation of the joint and surgical options in correcting related forefoot deformities. PMID- 11777232 TI - Effect of proximal articular set angle-correcting osteotomies on the hallucal sesamoid apparatus: a cadaveric and radiographic investigation. AB - A cadaveric and radiographic study was undertaken to demonstrate the change in intersesamoidal crista architecture after an osteotomy that corrects the proximal articular set angle (PASA). Three cadaveric first metatarsals with hallux valgus deformity were utilized. Separate Kirschner wires representing the longitudinal axis bisection, PASA, and the long axis of the crista were placed into each specimen. After osteotomy, the metatarsal heads were translated laterally, rotated parallel to the transverse plane to correct PASA, and impacted. The relationship between the crista and the long axis of the metatarsal was determined. A deviation in the alignment between the intersesamoidal crista and the long axis of the metatarsal following the osteotomy was observed. The radiographic portion of this study correlated intermetatarsal angle, PASA, and tibial sesamoid position with intersesamoidal crista appearance on sesamoidal axial radiographs. Radiographic parameters in 19 patients (34 feet) were compared and two distinct patterns were evident: 1) A proximal articular set angle greater than 15 degrees was associated with complete crista erosion in 10 feet (91% of this subgroup); 2) a tibial sesamoid position greater than three was associated with partial or complete erosion in 17 feet (100% of this subgroup). A higher deviation of PASA and increased displacement of the sesamoidal apparatus correlated with crista erosion. These findings suggest that the crista fails to adapt with PASA as hallux valgus progresses and undergoes erosion instead. This study suggests that when correcting the PASA, misalignment of the sesamoid apparatus may lead to sub-first metatarsal arthrosis. PMID- 11777233 TI - Metatarsophalangeal joint capsule tears: an analysis by arthrography, a new classification system and surgical management. AB - Metatarsalgia is a common presenting symptom with an established list of differential diagnoses. The authors present a classification system and surgical treatment algorithm for chronic metatarsophalangeal pain due to metatarsophalangeal joint capsule tear. A series of 58 metatarsophalangeal joints with partial tear diagnosed by arthrogram and treated by surgical repair are reviewed. The authors propose a classification system based on preoperative arthrography and a surgical repair procedure for each type of three distinct patterns. A study was developed and funded to perform postoperative arthrograms on 15 patients who had undergone surgical repair using the procedures presented. The purpose of the study was to validate the utility of the arthrogram in the diagnosis and clarification of the nature of the capsular tear. The authors were also able to demonstrate that the arthrographic findings became normal postoperatively, and that surgical repair of a seemingly innocuous capsule tear relieves pain. Fifty-six patients in the series reported relief of their preoperative symptoms. Postoperative arthrograms in 15 patients demonstrated a normal pattern in 73%, 20% had decreased extravasation, and 7% were unchanged. PMID- 11777234 TI - A prospective comparison of wedge matrix resection with nail matrix phenolization for the treatment of ingrown toenail. AB - In a prospective study, 110 patients with ingrown toenails were operated on, 55 with wedge matrix resection (WMR) and 55 with nail matrix phenolization (NMP). The patients were randomized on the basis of their address. All patients were reviewed by questionnaire 4 weeks postoperatively to establish the degree of pain, time of pain relief, walking and working ability, and the presence of infection. Furthermore, they were examined clinically at a median follow-up time of 11 months postoperatively to evaluate recurrence rate, rate of spicula formation, and patient satisfaction with regard to cosmesis and symptom relief. The data were tested for statistical significance using the chi-square test and Mann-Whitney rank sum test. The recurrence rate of ingrown toenail for the WMR group was 5.5% (3 patients) with a spicula rate of 36% (20 patients) and a reoperation rate of 20% (9 patients). In the NMP group, there were no recurrences (p = n.s.), the spicula rate was 7.3% (4 patients) (p < .005) and no patients were reoperated on (p < .016). Patient satisfaction with less pain and earlier pain relief was greatest in the NMP group. These results indicate that nail matrix phenolization is an efficient therapy for ingrown toenails and may be preferable to nail wedge resection. PMID- 11777235 TI - Soft-tissue osteochondroma in the calcaneal pad: a case report. AB - Soft-tissue osteochondromas of the foot are infrequently occurring lesions. A 65 year-old woman presented with soft-tissue osteochondroma in the soft tissues superficial to the plantar aspect of the calcaneus. The mass was densely ossified without cortical destruction or other alteration in the adjacent calcaneal bone on x-rays and computed tomography images. A 99m Tc bone scan showed a focal area of an increased uptake at the site of the mass below the calcaneus. Magnetic resonance imaging demonstrated high signal mass on T1-weighted images, isointense to fatty marrow, adjacent to the thickened plantar aponeurosis. The mass was completely excised. Histologically, mature lamellar bone was seen centrally, and the periphery was capped with hyaline cartilage. Since the tumor was located in the plantar aponeurosis and comprised of a single nodule of well-developed bone with well-organized endochondral ossification, the pathogenesis of this lesion might be related to metaplasia. PMID- 11777236 TI - Tarsal tunnel syndrome secondary to an accessory muscle: a case report. AB - The flexor digitorum accessorius longus is a rare muscular anomaly that has been reported as one of the etiologies of tarsal tunnel syndrome. The authors provide a case report of a patient with tarsal tunnel syndrome that resolved with resection of the flexor digitorum accessorius longus. The patient remains asymptomatic 40 months following surgery. PMID- 11777237 TI - Treatment of recurrent neuroma of the interdigital nerve by implantation of the proximal nerve into muscle in the arch of the foot. AB - A prospective study was done to evaluate the results of treating recurrent "Morton's" neuroma by a technique that combined resecting the interdigital neuroma through a plantar approach and implantation of the proximal end of the nerve into an intrinsic muscle in the arch of the foot. As a part of this study, quantitative sensory testing was done for the medial plantar and medial calcaneal nerves. Seventeen recurrent interdigital neuromas were resected in 13 patients. Pain was identified on physical examination as being due to neuromas located in the first (one), second (six), third, (eight) and fourth (two) web spaces. Seven of the 13 patients were found to have, by quantitative sensory testing and physical examination, an associated tarsal tunnel syndrome responsible for symptoms related to numbness in the foot in addition to the pain of the recurrent neuroma. These patients had tarsal tunnel decompression at the time of the neuroma resection. At a mean follow-up time of 33.8 months (range 24-42 months), done by direct physician interview and examination, 80% of the patients had excellent relief of symptoms, returned to their regular job, and wore usual footwear. Twenty percent of the patients had good relief of symptoms, worked at a different job, and had to change their footwear. It is concluded that recurrent pain after a dorsal interdigital neurectomy can be treated successfully through a plantar approach with implantation of the proximal end of the nerve into an intrinsic muscle. This study also identified an association of tarsal tunnel syndrome in 54% of this series of patients with recurrent Morton's neuroma. PMID- 11777238 TI - Toxic shock syndrome originating from the foot. AB - The most familiar etiology of toxic shock syndrome (TSS) is that of menstruation and tampon use. Nonmenstrual TSS has been described in all types of wounds including postsurgical, respiratory infection, mucous membrane disruption, burns, and vesicular lesions caused by varicella and shingles. A case of TSS occurring in a diabetic male patient with foot blisters is presented. Early recognition by an infectious disease specialist and appropriate medical management led to complete recovery. There have been no reported cases of Staphylococcus aureus TSS originating in the foot to date. PMID- 11777239 TI - Medial incision approach to the first metatarsophalangeal joint. PMID- 11777240 TI - Verrucous carcinoma of the foot. PMID- 11777241 TI - Atrophic rhinitis: a review of 242 cases. AB - Atrophic rhinitis is a debilitating nasal mucosal disease of unknown etiology. It is characterized by progressive nasal mucosal atrophy, nasal crusting, fetor, and enlargement of the nasal space with paradoxical nasal congestion. Primary atrophic rhinitis has decreased markedly in incidence in the last century. This probably relates to the increased use of antibiotics for chronic nasal infection. Secondary atrophic rhinitis resulting from trauma, surgery granulomatous diseases, infection, and radiation exposure accounts for the majority of cases encountered by the rhinologist today. Excessive turbinate surgery has been both acquitted and accused in the literature as an etiology for secondary atrophic rhinitis. We saw 242 patients with the diagnosis of atrophic rhinitis between 1982 and 1999. The diagnosis was confirmed by physical examination, biopsy, and imaging studies. Patients were diagnosed with primary atrophic rhinitis if their condition developed in a previously healthy nose and secondary atrophic rhinitis if their condition developed after sinonasal surgery, trauma, or chronic granulomatous disease. Prevention and treatment of the disease is discussed. PMID- 11777242 TI - Complications in sinus surgery and new classification proposal. AB - Complication overviews may lead to measures directed toward quality improvement and to better information for patients. When evaluating the rhinological literature from 1979 to 1999, a detailed comparison could not be made because of differences in reporting. With the advent of electronically stored medical data, events can be registered better than before. To be able to compile very diverse data from electronic dossiers into concise overviews for feedback, a simple general scale with broad categories is needed. These feedback overviews enable insight in the complication rates of different kinds of sinus surgery and monitoring of changing trends in sinus surgery. An example of a general classification based on severity is presented for use when electronically storing medical data. This scale varies from adverse events (grade A) to death (grade D). A consensus on categorization of complications is a prerequisite for a valid comparison with other clinics. To instigate a discussion about consensus, this classification is presented as an example. Our proposal is presented together with an overview of sinus surgery complications in recent literature for reference. PMID- 11777243 TI - Anatomic variations of the lateral nasal wall in the computed tomography scans of patients with chronic rhinosinusitis. AB - The development of computed tomography (CT) technique results in the advance in visualization of the anatomic structures of the lateral nasal wall. It allows the anatomic variations of this region to be identified precisely, which is important in surgical treatment of chronic rhinosinusitis. The aim of this study was to determine the incidence of anatomic variations of the lateral nasal wall in a group of patients with chronic rhinosinusitis. The preoperative, frontal plane CT scans of the study group were evaluated using the method of the four-zone interpretation. The incidence of the anatomic variations of the lateral nasal wall was consistent with the results reported by other authors. PMID- 11777244 TI - Diabetes insipidus after pituitary surgery: incidence after traditional versus endoscopic transsphenoidal approaches. AB - The endoscopic transnasal approach is gaining increasing popularity as the surgical method of choice for treatment of pituitary lesions. Previous studies have shown advantages such as quicker recovery and fewer cosmetic, dental, and nasal complications. However, no study has compared the rate of diabetes insipidus (DI) between the traditional and endoscopic approaches. This study will examine the incidence of short- and long-term postoperative DI after transnasal pituitary surgery and compare it with the incidence after traditional transseptal surgery. Eighty-one patients underwent transnasal surgery for the management of pituitary lesions. Fifty-five had the traditional sublabial, transseptal, transsphenoidal surgery and 26 patients had the direct transnasal, transsphenoidal endoscopic procedure. The incidence of immediate postoperative DI was 36% in the traditional group and 15% in the endoscopic group. Short-term (>2 weeks) DI that required treatment occurred in 11 patients (20%) in the traditional group and 2 patients (7.6%) in the endoscopic group. Long-term (>6 months) incidence of DI was 7.2% in the traditional group and 3.8% in the endoscopic group. We found a decreased incidence of immediate DI after transnasal endoscopic pituitary surgery as compared with the traditional sublabial transseptal approach. However, the incidence of long-term DI was not significantly different in the two groups. PMID- 11777245 TI - Endoscopic transethmosphenoidal approach for pituitary tumors with image guidance. AB - The advantages of endoscopic transethmosphenoidal surgery for pituitary tumors using a navigation system were reported. The surgical technique was as follows. First, sphenoidal sinuses were opened via the bilateral ethmoidal sinuses and the olfactory clefts. Then the septum of the sphenoidal sinuses was resected. Next, an endoscope was inserted via the left nasal cavity and fixed in place. The tumor was then removed via the right nasal cavity. Our approach for pituitary tumors provided sufficient working space and permitted the surgeon to carry out the procedure using both hands. In addition, use of the InstaTrak System made it possible to recognize the orientation of the surgical field in the sella turcica. Thus, the tumor could be resected more easily and safely. It is concluded that this approach will be particularly useful for patients with narrow nasal cavities or poor development of the paranasal sinuses. PMID- 11777246 TI - Allergic rhinitis as a risk factor for orbital complication of acute rhinosinusitis in children. AB - The purpose of this article is to determine allergic rhinitis and age as potential risk factors for the development of orbital complications of acute rhinosinusitis in children. One hundred two children presenting with orbital swelling were investigated by computed tomography (CT) of the paranasal sinuses and the orbit as well as for underlying allergic rhinitis. Sixty (58.8%) patients had orbital complications of clinical and radiological acute rhinosinusitis. They were grouped accordingly: preseptal cellulitis (n = 24), periostitis (n = 10), and subperiosteal abscess (n = 26). No abscess within the orbit or cavernous sinus thrombosis was found. Thirty-four (56.7%) of the 60 patients underwent allergy investigation. Allergic rhinitis was found in 9 (64.3%) of 14 children with preseptal cellulitis, in 1 (25%) out of 4 children with periostitis, and in 13 (76.5%) out of 17 children with subperiosteal abscess. The prevalence of allergic rhinitis was significantly higher in patients presenting in pollen season from February to August (17:4) than in patients presenting in the period between September and January (6:7). Thus, allergic rhinitis may be a cofactor in the pathogenesis of orbital complications of acute rhinosinusitis. According to our study population, age only influences the type of orbital complication of acute rhinosinusitis in the sense that older children are more likely to develop subperiosteal abscess, whereas younger children develop preseptal cellulitis. PMID- 11777247 TI - Safety of steroid injections in the treatment of nasofrontal recess obstruction. AB - A retrospective review was undertaken to determine if steroid injection is a safe and effective intervention in the management of chronic nasofrontal recess obstruction. Seventy-four patients were identified who had undergone prior endoscopic sinus surgery and subsequently developed nasofrontal recess obstruction that was treated with injection of Kenalog 20 mg/mL (Bristol-Myers Squibb Co., Princeton, NJ) directly into the polyps or fibrosis. The study included 38 men and 36 women with a mean age of 45.4 years. These patients collectively underwent 687 injections, an average of 9.3 injections per patient. The indication was polyposis in 70 patients and fibrosis in 17 patients, with 13 sharing both indications. These patients also required 112 office procedures to maintain nasofrontal recess patency, an average of 1.5 procedures per patient. Three patients eventually required frontal sinus obliteration. The mean follow-up period from the initial injection was 50.1 months, and no complications were reported. Therefore, nasofrontal steroid injection appears to be safe and effective in the treatment of nasofrontal recess obstruction. PMID- 11777248 TI - An immunohistological study of the localization characteristics of thymus and activation-regulated chemokine in the allergic inferior turbinate mucosa with reference to the effectiveness of trichloroacetic acid treatment. AB - To investigate the background of the effectiveness of trichloroacetic acid (TCA) treatment, we examined the localization of thymus and activation-regulated chemokine (TARC) on allergic inferior turbinate mucosa using immunohistological methods. After obtaining informed consent, only one side of the inferior turbinate was treated with 80% (wt/vol) TCA solution under topical anesthesia using 4% lidocaine with epinephrine in 19 cases of allergic rhinitis. Among those, 17 cases did not show clinical improvement and underwent nasal septal reconstruction surgery and turbinectomy. Bilateral inferior turbinate specimens were obtained. The untreated turbinate specimens showed positive TARC findings. The positive findings were confirmed in the outer side of cytoplasm in the stratified ciliated columnar epithelium but not in the goblet cell. In the lamina propria, the glandular tissue and afew of the infiltrated lymphocytes just beneath the epithelium up to the depth of 120 microm were found TARC-positive (TARC+). The average number of positive cells in one microscopic visual field using 100x magnification was 3.97 +/- 4.04. On the other hand, the epithelium of the TCA-treated side showed positive findings only in two cases. The TCA-treated side also showed a relative decrease in infiltrated cells. Even in areas where there still were infiltrated cells, they were confirmed to be TARC-negative (TARC ) after TCA treatment. It is considered that the regenerated epithelium after TCA treatment originates from the glandular epithelium with negative TARC expression existing in the area deeper than a 120-microm level and that this immunohistological change would lead to the effectiveness of TCA treatment. PMID- 11777249 TI - Relationship between subjective nasal stuffiness and nasal patency measured by acoustic rhinometry. AB - Nasal geometry measured by acoustic rhinometry was compared with the subjective sensation of nasal stuffiness in healthy subjects before and after provocation with histamine. The correlation was poor at rest, but it was significant after histamine provocation in children and adults. It is easier to find a relationship between subjective and objective nasal obstruction afer inducing congestion. (American Journal of PMID- 11777250 TI - Intranasal application of the alpha2-adrenoceptor agonist BHT-920 produces decongestion in the cat. AB - The effect of alpha2-selective adrenoreceptor activation on nasal cavity dimension in an experimental model of congestion has not been defined. Presently, we used acoustic rhinometry to evaluate the decongestant activity of BHT-920, a selective alpha2-adrenergic agonist against nasal congestion produced by intranasal compound 48/80. Administration of the mast cell liberator compound 48/80 (1%) into a nasal passageway decreased ipsilateral volume and minimum cross sectional area by 73 +/- 4% and 42 +/- 6%, respectively. The congestant effect of compound 48/80 was blocked by topical BHT-920 (0.3 and 1%) in a dose related manner. In addition, the decrease in minimum cross-sectional area produced by compound 48/80 was attenuated after topical BHT-920 treatment. As a comparison we also evaluated the topical decongestant activity effects of the alpha1-adrenergic agonist phenylephrine, and the nonselective alpha-agonist oxymetazoline. Both phenylephrine (0.1-1.0%) and oxymetazoline (0.01-0.3%) produced decongestion. The blood pressure effects of these three drugs also were evaluated. At doses of 0.3 and 1.0%, BHT-920 did not produce hypertension. In contrast, oxymetaZoline (0.01 0.1%) produced a transient hypertension that peaked at 15 minutes and fully recovered 45 minutes after administration. The hypertensive effect of phenylephrine at 0.3 and 1.0% lasted over 60 minutes. The present findings indicate that selective alpha2-agonists may produce decongestant activity with an improved cardiovascular profile compared with current sympathomimetic drugs such as phenylephrine. PMID- 11777251 TI - Presence and characterization of sensitization to staphylococcal enterotoxins in patients with allergic rhinitis. AB - Exotoxins derived from Staphylococcus aureus appear to be involved in the pathogenesis of allergic diseases, especially atopic dermatitis (AD). However, little is known about sensitization to enterotoxins in cases of respiratory allergies. Because the nasal cavity is a primary site of colonization by S. aureus, we sought to determine the prevalence and role of serum immunoglobulin E (IgE) antibodies against staphylococcal enterotoxin A (SEA) and SEB in patients with allergic rhinitis (AR). The presence of SEA- and SEB-specific IgE was determined in 40 patients with AR and 16 healthy control subjects. In the rhinitis group, nasal symptom score, total serum IgE, sensitization to other inhaled allergens and the presence of sinusitis were determined. Twenty-five percent of patients with AR were sensitized to SEA/SEB whereas 6.3% of controls were sensitized to the toxins. Sensitization to SEB was predominant relative to SEA. There were no significant differences in the severity of nasal symptoms and complications of other allergic diseases including AD and bronchial asthma, between patients with or without sensitization to SEA/SEB. However, patients sensitized to these toxins were likely to show increased total serum IgE and polyvalent sensitization, suggesting that exposure and subsequent sensitization to SEA/SEB may be involved in polyvalent sensitization. PMID- 11777252 TI - Autistic syndrome. PMID- 11777253 TI - Predicting spoken language level in children with autism spectrum disorders. AB - Thirty-five children who received an autism spectrum diagnosis at the age of 2 years (24 with autism, 11 with PDD-NOS) were re-evaluated 2 years later to examine factors related to the development of spoken language. Child variables (play level, motor imitation ability and joint attention) and environmental variables (socioeconomic status and hours of speech/language therapy between ages 2 and 3) were used to predict an aggregate measure of language outcome at age 4. After controlling for age 2 language skills, the only significant predictors were motor imitation and number of hours of speech/language therapy. Implications of these results for understanding the early developmental course of autism spectrum disorders and the effects of intervention are discussed. PMID- 11777254 TI - The Scottish Centre for Autism preschool treatment programme. I: A developmental approach to early intervention. AB - Early intervention is an area of intense current interest for parents and professionals. This article describes a mainstream National Health Service (NHS) approach to early intervention, developed at the Scottish Centre for Autism. The aims of treatment are to improve the child's early social communication and social interaction skills, leading to the potential development of play and flexibility of behaviour. This is achieved by 1:1 intensive treatment by trained therapists, and a schedule of parent training. The treatment protocol incorporates a child led approach; the use of imitation as a therapeutic strategy; using language contingent on activities; and the introduction of flexibility into play and social exchanges. PMID- 11777255 TI - Increasing joint attention, play and language through peer supported play. AB - The purpose of the present study was to examine the effects of participation in an integrated play group on the joint attention, symbolic play and language behavior of two young boys with autism. Two 6-year-old twin brothers participated in this study, along with three typically developing girls, ages 5, 9 and 11. A multiple baseline design was used with three phases: no intervention, intervention with adult coaching, and intervention without adult coaching. After being trained, the three typically developing children implemented the integrated play group techniques in 30 minute weekly play group sessions for over 16 weeks. Results indicate that participation in the integrated play group produced dramatic increases in shared attention to objects, symbolic play acts, and verbal utterances on the part of the participants with autism. These increases were maintained when adult support was withdrawn. Implications of these findings for inclusion of children with autism are discussed. PMID- 11777256 TI - Monitoring the progress of preschool children with autism enrolled in early intervention programmes: problems in cognitive assessment. AB - This report examines how conclusions about the progress of preschool children enrolled in early intervention programmes may be influenced by the use of different cognitive assessment tools. As part of a longitudinal treatment outcome study, 24 children with autism aged between 27 and 58 months were each tested on the Bayley, Merrill-Palmer and Vineland scales. Their performance on each of these tests was compared. Results showed that, while scores on the different tests were highly correlated, actual test scores varied considerably, with the Bayley tending to produce the lowest IQ scores and the Merrill-Palmer the highest. These findings have important implications, as it is evident that judgements about the effects of therapy may be significantly influenced by the selection of the tests for pre- and post-treatment assessments. Possible ways of collecting, recording and reporting test data, so as to avoid spurious conclusions about treatment effects, are discussed. PMID- 11777257 TI - Predictors of treatment outcome in young children with autism: a retrospective study. AB - This study examined predictors of developmental outcomes in 17 children diagnosed with autism or PDD-NOS, who received generic treatment over a mean period of 37 months. Pre-treatment evaluations occurred at a mean age of 31 months with follow up evaluations at a mean age of 69 months. Significantly different developmental trajectories were observed among the participants at follow-up, separating the participants into two distinct groups (high and low outcome). However, groups did not differ significantly in treatment intensity or other outcome prediction measures. Pre-treatment developmental intelligence levels between the two groups approached significance. The results raise questions regarding the effect of treatment intensity and type, family stress factors, and intelligence ability in very early childhood on, outcome. PMID- 11777258 TI - Outcome survey of early intensive behavioral intervention for young children with autism in a community setting. AB - This article presents findings from an outcome survey of the effects of early intensive behavioral intervention (EIBI) for young children with autism in a community setting. Results from both individual case reviews and parent questionnaires are presented, with the data failing to support any instances of'recovery' while still yielding a high degree of parental satisfaction with the treatment. Moreover, a follow-up inquiry into the type of services each child was receiving in his or her post-EIBI setting documents continued dependence on extensive educational and related developmental services, suggesting that the promise of future treatment sparing did not materialize. Limitations of the survey in evaluating community-based EIBI services are discussed along with the need for further research designed to document the effectiveness of services provided to young children with ASD in the community. PMID- 11777259 TI - New evidence for the efficacy of combination therapy in onychomycosis. PMID- 11777260 TI - Topical amorolfine for 15 months combined with 12 weeks of oral terbinafine, a cost-effective treatment for onychomycosis. AB - OBJECTIVE: This open randomized study examined the efficacy of a combination of oral terbinafine and topical amorolfine in the treatment of severe dermatophyte toenail onychomycosis with matrix area involvement. PATIENTS/METHODS: A total of 147 patients were randomized to one of three treatment groups: 15 months of once weekly topical amorolfine lacquer in combination with 6 weeks (Group AT6) or 12 weeks (Group AT12) of oral terbinafine, 250 mg once daily: or terbinafine monotherapy for 12 weeks (Group T12). Patients were followed for a total of 18 months. The primary efficacy variable was the result of mycological examination after 3 months of therapy; secondary efficacy variables were mycological and clinical examination at 3-monthly intervals, with an additional clinical evaluation at 18 months. Safety and tolerance were also assessed. RESULTS: Negative mycological results, assessed at 3 months, were recorded for 14 of 40 patients (35%) in Group AT6, 11 of 44 (27.5%) in Group AT12 and 7 of 41 (17.1%) in Group T12. At 18 months, the global response (mycological and clinical cure) was seen in 22 of 50 patients (44%), 34 of 47 (72.3% and 18 of 48 (37.5%) in the AT6, AT12 and T12 groups, respectively. CONCLUSIONS: These results suggest that a combination therapy regime with oral and systemic treatment is superior in efficacy to monotherapy with a systemic drug alone in the treatment of severe onychomycosis. In addition, the cost per cure ratio was better in the combination groups. PMID- 11777261 TI - Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain. AB - OBJECTIVE: In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy. PATIENTS/METHODS: A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group 1-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed. RESULTS: At week 12, mycological cure was attained in 42 of 45 patients (93.3%) in group AI-6, 29 of 35 patients (82.9%) in group AI-12, and 14 of 34 patients in group 1-12. The difference between both combination groups and the control group were significant (P < 0.001). The global cure rate at week 24 was 83.7% (36 patients) in group AI-6, 93.9% (31 patients) in group AI-12, and 68.8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant (P < 0.05). CONCLUSIONS: These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis. PMID- 11777262 TI - The future of onychomycosis therapy may involve a combination of approaches. AB - Onychomycosis is a fungal infection of the nail unit, most commonly caused by the anthropophilic dermatophyte fungi. It is generally accepted that this disease is increasing in prevalence despite the introduction of new and efficacious antifungal drugs. Several studies have documented health-related quality-of-life issues associated with onychomycosis and it is clear that patient treatment is both necessary and desirable. The aetiology and pathogenesis of onychomycosis is coming under increasing scrutiny and work in this field has grown substantially in recent years. This is reflected by the increased assurance with which clinicians can now prescribe treatment and be confident of improvement in a majority of their patients. However, a significant proportion of patients, perhaps as many as 25-40% of those encountered in clinical practice, are classified as treatment failures. Clinical indicators for poor prognosis include the development of residual foci of subungual fungal growth, onycholysis and severe disease. These observations have led to a resurgence of interest in combination treatments for use in patients at risk of failure/relapse. Several types of combination can be considered, including the use of oral or topical drugs and the concomitant use of surgical techniques, all of which have a place in the treatment of onychomycosis. PMID- 11777264 TI - Cellular therapy: an introduction. AB - Cellular therapy is defined as the transfer, to the intact host, of living cells with the intent of introducing new host functions or correcting defective functions. The appeal and the promise of cellular therapy derive from the ability to manipulate, ex vivo, cellular and molecular biologic pathways in a way that is not possible in the intact organism. PMID- 11777263 TI - The rationale for combination therapy. AB - Fungal infections of the nail are common in European populations. There are a number of clinical presentations usually resulting from an infection by one of the dermatophyte species, notably Trichophyton rubrum. A number of modern treatment strategies are available and are generally well tolerated and effective. However, a significant proportion of patients, 20-30%, can expect treatment failure and/or relapse following treatment. The search for new treatment modalities and drugs is hampered by our lack of understanding of the basic pathophysiological mechanisms that underlie these frequently encountered infections. A correct diagnosis is key to the implementation of successful treatment. Even then, some infections do appear to be more recalcitrant than others. This may be the result of a number of interacting factors: patient susceptibility, fungal growth patterns that resist treatment and the occurrence of dormant fungal spores (arthrospores) in the nail. Increasingly, research is turning towards the identification of clinical indicators of poor prognosis and the development of new treatment strategies to overcome them. The combination of drugs to produce synergistic activity is one possible advance towards achieving higher cure rates. PMID- 11777266 TI - Challenges associated with the development, manufacturing, and delivery of cellular medicines. AB - As the potential of these exciting therapeutics approaches reality, the challenges associated with their discovery, approval, and widespread distribution are just now being realized. The current health care infrastructure is unable to accommodate the complexity of cellular therapy, which exceeds the capability of existing treatment facilities to provide ready access for patients to receive standardized collections for consistent quality of apheresis product and the most consistently acceptable and potent therapeutic agent. The goal is to develop a system for seamless international access to cellular therapies and will involve the unification of the systems for the collection of patient-specific cellular materials, the development of an international network of FDA (and other regulatory agencies) registered facilities, the preservation of patient-specific product control from acquisition to re-infusion, the integration of a sophisticated transportation network to meet the time and environment-critical nature of the raw materials and the finished product, and the development of a comprehensive informatics system to coordinate all of the elements. PMID- 11777265 TI - Dendritic cell-based treatment of cancer: closing in on a cellular therapy. AB - PURPOSE: Dendritic cells are the most potent antigen-presenting cells and are critical to initiation of immune responses. Dendritic cells loaded ex vivo with tumor-associated antigen are being administered to cancer patients in an effort to jump-start a potent, cell-mediated anticancer immune response resulting in tumor shrinkage and clinical benefit. PATIENTS AND METHODS: Dendreon Corporation has designed three therapeutic vaccines using blood-derived dendritic cells loaded ex vivo with antigen: Provenge for prostate cancer; Mylovenge for multiple myeloma and other B-cell malignancies; and APC8024 for cancers expressing the HER 2/neu proto-oncogene. RESULTS: Preclinical studies demonstrated that blood dendritic cells matured spontaneously in short-term culture without growth factors, and that fusion of antigens with granulocyte-macrophage colony stimulating factor enhances antigen uptake and presentation by blood dendritic cells. Phase I/II trials suggest that these dendritic cell-based vaccines are safe and well tolerated. Provenge has demonstrated antitumor activity in hormone refractory prostate cancer; approximately 20% of patients experienced decreased prostate-specific antigen (i.e., PSA) levels and a similar percentage experienced disease stabilization. Double-blind, placebo-controlled, randomized trials in metastatic, asymptomatic hormone-refractory prostate cancer have been initiated. Phase II data on Mylovenge are similarly encouraging, and expanded phase II testing is ongoing in anticipation of opening phase III trials in 2002. APC8024 is in early clinical development and has shown significant capacity to elicit antigen-specific immune responses. CONCLUSION: Antigen delivery by ex vivo antigen-loaded dendritic cells may be an effective approach to cancer immunotherapy. PMID- 11777267 TI - The promise of T-lymphocyte immunotherapy for the treatment of malignant disease. AB - Exciting developments in basic immunology and tumor biology have increased our understanding of mechanisms of interactions between tumor cells and the immune system. The rapid translation of bench research to clinical applications has led to immense progress in the field of cellular immunotherapy. The rationale for the use of T cells for adoptive transfer is that tumors are immunogenic and that the transferred cells have the capacity to recognize tumor cells and elicit an immune response that leads to specific tumor cell killing. Additionally, adoptive therapy may have a role in replacing, repairing, or enhancing the immune function damaged as a consequence of cytotoxic therapy for the malignant disease itself. PMID- 11777268 TI - Mesenchymal stem cells: stealth and suppression. AB - Human post-natal bone marrow contains mesenchymal stem cells (MSCs), which are capable of giving rise to multiple mesenchymal cell lineages. Large quantities of human MSCs can be readily obtained following a simple bone marrow aspiration procedure and subsequent expansion over a million-fold in culture. This extensive capacity for clinical scale expansion in vitro has facilitated the development of preclinical models as well as clinical studies designed to assess the safety, feasibility, and efficacy of transplanting allogeneic MSCs for a variety of indications. This review focuses on the rationale for performing clinical studies of MSC transplantation and will discuss the potential role that MSCs may have in the field of hematopoietic stem cell transplantation as well as for the repair or regeneration of bone, cartilage, and cardiac tissues. PMID- 11777269 TI - Human embryonic stem cells: culture, differentiation, and genetic modification for regenerative medicine applications. AB - Human embryonic stem (hES) cells can proliferate extensively in culture and can differentiate into representatives of all three embryonic germ layers in vitro and in vivo. The undifferentiated hES cells have now been cultured for more than 50 passages in vitro, yet maintain a normal karyotype. The hES cells express a series of specific surface antigens, as well as OCT-4 and human telomerase, proteins associated with a pluripotent and immortal phenotype. On differentiation, OCT-4 and human telomerase expression decreases with the emergence of a maturing population of cells. During hES cell differentiation, modulation of the expression of many genes has been evaluated using microarray analysis. To improve the ease, reproducibility, and scalability of hES culture, methods have been developed to propagate the cells in the absence of mouse embryonic cell feeders. hES cells maintained in culture using extracellular matrix factors together with mouse embryonic cell conditioned medium proliferate indefinitely while maintaining a normal karyotype, proliferation rate, and complement of undifferentiated cell markers. hES cells cultured without feeder layers retain their capacity to differentiate into cells of all three germ layers in vitro and in teratomas. The hES cells can also be genetically modified transiently or stably using both plasmid and viral gene transfer agents. These analyses and technological developments will aid in the realization of the full potential of hES cells for both research and therapeutic applications. PMID- 11777270 TI - The frontier of cellular medicine: expanding umbilical cord blood stem cells for clinical use. PMID- 11777271 TI - Validation of a multicolor interphase fluorescence in situ hybridization assay for detection of transitional cell carcinoma on fresh and archival thin-layer, liquid-based cytology slides. AB - OBJECTIVE: To evaluate the feasibility of performing multicolor interphase fluorescence in situ hybridization (FISH) on ThinPrep slides of transitional cell carcinoma (TCC). STUDY DESIGN: Slides from 20 voided urine specimens were prepared by the ThinPrep technique (Cytyc, Boxborough, Massachusetts, U.S.A.), pretreated using a pretreatment kit and subjected to hybridization with the multicolor FISH probe UroVysion (Vysis, Downers Grove, Illinois, U.S.A.). Archival slides were placed in xylene, destained in alcohol and washed prior to pretreatment. Urines from patients with cytology-positive, biopsy-proven grade 1 (n = 5), 2 (n = 7) and 3 (n = 5) TCC and negative cytology and biopsy (n = 3) were selected. Freshly prepared (n = 10) and archival (n = 10) slides were used. RESULTS: All carcinoma cases were FISH positive (> 5 cells with complex abnormalities of > or = 2 studied chromosomes per slide). None of the normal samples were aneusomic. Gain of chromosomes 3, 7 and 17 constituted the majority of positive cases. Proper destaining and slight decrease in stringency wash conditions enabled reliable detection of signals in archival cases. CONCLUSION: Routine ThinPrep slides can be used for multicolor interphase FISH analysis of urine cytology specimens. Archival slides provide the opportunity to analyze by FISH the nature of atypical cells identified by cytology. This revised method allows FISH technology more accessibility for routine use in cytology laboratories. PMID- 11777272 TI - Correlation between AgNOR count and subjective AgNOR pattern assessment score in cytology and histology of breast lumps. AB - OBJECTIVE: To find the correlation of argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytology and histology of breast lumps. STUDY DESIGN: The study group consisted of 73 patients (46 malignant, 27 benign) with breast lumps. In all cases, fine needle aspiration cytology (FNAC) samples and histologic specimens were studied by conventional and silver staining for AgNORs. RESULTS: AgNOR count and SAPA score were helpful in differentiating benign from malignant tumors in both the cytologic smear and histologic specimen. AgNOR count was 6.94+/-2.74 in FNAC and 6.57+/-2.73 in histology of malignant tumors, while in benign tumors it was 2.75+/-0.74 in FNAC and 2.68+/-0.77 in histology. SAPA score was 9.02+/-4.60 in FNAC and 8.76+/-2.34 in histology in malignant tumors and 5.87+/-0.93 in FNAC and 5.82+/- 0.83 in histology in benign tumors. CONCLUSION: Both AgNOR count and SAPA score gave similar results, but SAPA score is a more convenient, reproducible and rapid method of AgNOR evaluation. PMID- 11777273 TI - Nonaspiration fine needle cytology and its histologic correlation in canine skin and soft tissue tumors. AB - OBJECTIVE: To analyze the findings of nonaspiration fine needle (NAFN) cytology as compared with the histopathologic findings in evaluating canine skin and soft tissue tumors. STUDY DESIGN: NAFN (21-27 gauge) cytology was performed on 213 cases. Smears were air dried and stained by the Rosenfeld method (May-Grunwald Giemsa modification). Histopathologic evaluation was available for comparison in 40% of cases. RESULTS: NAFN cytology and histopathology results were compared in 85 dogs. The size of the 117 lesions varied from 0.5 to 2 cm (n=39), 2.1 to 5 cm (n=43), and > or = 5.1 (n=35). There were 22 nonneoplastic lesions, mostly inflammatory processes and cysts. Neoplastic lesions were classified as epithelial (36%), mesenchymal (30%), round cell tumor (n=13) and melanocytic (2%). Among 40 malignant lesions, mast cell tumor (n=14) and hemangiopericytoma (n=9) were the most frequent. Lipoma (n=14) and trichoblastoma (n=10) were the most common benign neoplastic lesions. Cytology showed sensitivity of 89%, specificity of 100%, positive and negative predictive value of 100% and 96%, respectively, and efficacy of 97%. CONCLUSION: NAFN cytology is extremely useful and accurate. It is safe and avoids the use of anesthesia. Further, it is easy to perform and noninvasive and usually provides a high-quality sample. PMID- 11777274 TI - Utility of thyroid transcription factor-1 and cytokeratin 7 and 20 immunostaining in the identification of origin in malignant effusions. AB - OBJECTIVE: To estimate the utility of thyroid transcription factor-1 (TTF-1) and the combined cytokeratin 7 (CK7) and 20 (CK20) immunoprofile as a marker for identifying the primary site of metastatic adenocarcinoma in effusions of the serous cavity. STUDY DESIGN: Formalin-fixed, paraffin-embedded cell block specimens of pleural and peritonealfluid diagnosed as metastatic adenocarcinomas with known sites of origin were used for TTF-1, CK7 and CK20 immunohistochemistry. The primary sites of these cases were lung (16 cases), ovary (15), stomach (9), colon (8) and breast (8) and were confirmed by radiologic and/or histologic evaluation. RESULTS: The lung adenocarcinomas showed TTF-1 positivity in 81% (13/16) of cases. All nonpulmonary adenocarcinomas lacked TTF-1 staining. The CK7-/CK20+ immunophenotype was seen in 63% of colonic adenocarcinomas and not seen in lung, ovary, stomach or breast adenocarcinomas. The CK7+/CK20- immunophenotype was seen in 100%, 88% and 87% of cases that originated in the lung, breast and ovary, respectively. CONCLUSION: TTF-7 immunostaining is useful in the differentiation between pulmonary and nonpulmonary origin of adenocarcinomas in malignant effusions. The combination of CK7-/CK20+ immunostaining is useful in identifying colon adenocarcinomas. PMID- 11777275 TI - Flow cytometric immunophenotyping and comparison with immunocytochemistry in small round cell tumors. AB - OBJECTIVE: To quantitate different antigens by flow cytometric immunophenotyping (FCI) in small round cell tumors (SRCTs) and to compare the FCI technique with immunocytochemistry (IC). STUDY DESIGN: IC and FCI were performed on 24 consecutive cases of SRCT on fine needle aspiration biopsy material using a panel of antibodies--e.g., cytokeratin (CK), leukocyte common antigen (LCA), desmin, epithelial membrane antigen, neuron-specific enolase, chromogranin, retinoblastoma gene product, neuroblastoma clone (NB84a (NB), vimentin and Mic-2 gene product. IC was done by indirect immunoperoxidase and FCI by indirect immunofluorescence onflow cytometry. RESULTS: In Ewing's sarcoma, with the help of FCI, positive results were obtained in an additional 4 samples in CK, 2 samples in actin and 3 samples in desmin. Similarly, one each sample was additional positive regarding Mic-2 and vimentin by IC. In cases of neuroblastoma with the help of FCI, additional positive results were obtained in one each sample of CK, LCA and NB and two in actin. Combined use of FCI and IC helped to show chromogranin positivity in an additional two cases. Divergent differentiation was noted in four cases of Ewing's sarcoma, one neuroblastoma and two peripheral neuroectodermal tumors. CONCLUSION: FCI technique is sensitive, more objective and quantitative in comparison with manual absorbance-based microscopic detection of enzyme immunohistochemistry products. FCI may determine divergent differentiation in SRCTs. PMID- 11777276 TI - Mean nuclear area of squamous cell carcinomas of the head and neck using image cytometry. AB - OBJECTIVE: To determine if mean nuclear area (MNA) in squamous cell carcinomas of the head and neck (SCCHN) correlate with the TNM system and histologic grade. STUDY DESIGN: We measured MNA by image cytometry on 74 primary SCCHN. Fify-five had primary surgery, 16 had radiotherapy, and 3 and both as their primary treatment. RESULTS: The mean MNA was 47.85 microm2 (range, 20.5-84.8). Tumor size, nodal status and histologic grade were, respectively: T1 = 13, T2 = 29, T3 = 18, T4 = 14; N0 = 53, N1 = 15, N2 = 5, N3 = 1; 17 = well, 38 = moderate, 19 = poorly differentiated. Spearman rank and Kruskal-Wallis tests for MNA/histologic grade, MNA/tumor size, MNA/nodal status and MNA/site were calculated; only MNA/node was statistically significant (P<.05). CONCLUSION: MNA increases in primary SCCHN as nodal involvement increases. This may reflect that high MNA may be a biologic marker of primary SCCHN with a poorer prognosis. PMID- 11777277 TI - Nuclear chromatin characteristics of breast solid pattern ductal carcinoma in situ. AB - OBJECTIVE: To characterize nuclei from breast solid pattern ductal carcinoma in situ (DCIS) by their karyometric features and to search for the presence of statistically significantly different subsets of nuclei. STUDY DESIGN: One hundred nuclei from each of 6 normal, 13 solid DCIS, (9 low and intermediate grade and 4 high grade DCIS) histopathologic samples of breast tissue were digitally recorded. Karyometric features were computed and subjected to a nonsupervised learning algorithm (P-index) to identify significantly different subgroups. RESULTS: Nuclei in low grade lesions displayed a diploid/near diploid pattern, while the majority of intermediate grade lesions fell into a range beyond 5N. The high grade lesions showed substantial genomic instability and represented three statistically different subsets or phenotypes. CONCLUSION: There is a progression of nuclear abnormality from low grade to high grade DCIS. The nuclei from high grade DCIS form a heterogeneous set that represents three phenotypes. One of these phenotypes shows a nuclear chromatin pattern that more closely resembles poorly differentiated, infiltrating disease. The observation of such a phenotype may have prognostic implications. PMID- 11777278 TI - Establishment of a diploid reference value for DNA ploidy analysis by image cytometry in mouse cells. AB - OBJECTIVE: To establish a diploid reference value for DNA ploidy analysis of mouse cells (Mus musculus) by image cytometry using the CAS 200, an analysis system suitable for DNA content studies in human cells. STUDY DESIGN: To establish this standard, we used spleen imprints from 26 normal animals. A minimum of 150 lymphocytes present in each imprint was counted. The mean DNA content (pg/cell) of the G0/G1 peak and the DNA index observed in all samples were statistically analyzed. Cytospins with peritoneal cells from the same animals were then analyzed with this reference DNA value to confirm the diploid range. RESULTS: The DNA diploid reference value was determined by the mean DNA content of all spleen samples, which was 6.42 +/- 0.234 pg/cell, and the diploid range, defined as the diploid value +/- 10%, was 5.78-7.06 pg/cell. All the peritoneal samples showed a DNA diploid histogram, with a mean value for the G0/G1 peak DNA content of 6.742 +/- 0.15. CONCLUSION: The diploid reference value found in this study differs from those reported for other species, including the human being, and should be used in further studies of mouse pathology. PMID- 11777279 TI - Limited value of PCNA immunohistometry on tru-cut biopsies in inflammatory and cirrhotic liver disease. PMID- 11777280 TI - Characteristics of nitric oxide-induced apoptosis and its target cells in mitogen stimulated peripheral blood mononuclear cells from HIV+ subjects. AB - The phenomenon of apoptosis observed in lymphoid cells from HIV+ subjects is an important factor contributing to their massive depletion. Several studies have identified nitric oxide (NO) as one of the molecules involved in the apoptosis phenomenon observed during HIV infection. It has been shown that HIV-derived gp120 enhances NO synthesis in cultured cells from HIV+ individuals. Therefore, we tested the potential of two nitric oxide synthase (NOS) inhibitors with different mechanisms of action as preventive agents of in vitro apoptosis, in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. PBMC isolated from these patients always showed higher apoptosis levels than normal subjects, a fact that correlated with overproduction of NO and with reduction of mitochondrial transmembrane potential in these cells. We identified the CD8+ T lymphocyte sub population as the major apoptosis target in PBMC cultures. Treatment with NO inhibitors N(G)-monomethyl-L-arginine (L-NMMA) and dexamethasone (DEX) inhibited spontaneous and mitogen-induced apoptosis, while reducing mitochondrial alterations in PBMC from both normal (30%) and HIV+ (70%) subjects. The development of apoptosis in target cells correlated with their mitochondrial transmembrane potential impairment and with increased expression of Fas (CD95) molecules. These results offer additional alternatives for the manipulation of cellular depletion in HIV disease. PMID- 11777281 TI - Co-operation of IL-1 and IL-2 on T-cell activation in mononuclear cell cultures. AB - In search of an optimized anti-cancer immunotherapy, the combination of IL-2 and IL-1 has been tried. In an in-vitro LAK model, this cytokine cocktail seemed to be quite promising. In our in-vitro model of IL-2 induced T-cell activation we have therefore investigated the co-operation of these two potent immunostimulators. Mononuclear cells were stimulated with CD3 activating antibody in the presence of different cytokines and blocking or neutralizing antibodies. Cytokine concentrations were detected in the supernatants with ELISA. Intracellular IFN-gamma and IL-4 in the different T-cell subsets was measured by flow cytometry. IL-1 and IL-1 receptor antagonist (IL-1Ra) were up-regulated by IL-2, this was achieved independently of IL-12 or CD40/CD40L interaction. As a negative feedback mechanism, IL-1beta induced its natural antagonist, IL-1Ra. Both endogenous and exogenous IL-10 suppressed IL-1beta and induced IL-1Ra, thus markedly decreased the amount of functional IL-1. The combination of IL-2 and IL 1beta lead to a mildly increased Interferon-gamma (IFN-gamma) secretion (+20%, p < 0.05), however, this appeared to be the result of an increased IFN-gamma production per secreting cell, rather than of an increased recruitment of non secreting cells. Similarly, IL-6 was also induced in an additive fashion (+30%, p < 0.05). For both cytokines, this effect could be significantly augmented by neutralizing IL-1Ra. Concentrations of IL-2 induced IL-10 and soluble Fas ligand (sFasL) were not affected by IL-1beta. We were thus able to demonstrate that IL-1 relays its activity through different pathways than IL-2. Furthermore, we could show that the potentially synergistic action of IL-2 and IL-1 was hindered by the simultaneous induction of signficant amounts of IL-1Ra. From the latter findings we conclude that the combination of IL-2 and IL-1 for cytokine-induced anti-tumor activity may not, but a combination of IL-2 and anti-IL-1Ra might prove beneficial. PMID- 11777282 TI - Regional variations in the distribution of small intestinal intraepithelial lymphocytes in alymphoplasia (aly/aly) mice and heterozygous (aly/+) mice. AB - Regional variations in intraepithelial lymphocytes (IELs) in the small intestine were examined in alymphoplasia mutant (aly/aly) mice, which are characterized by the systemic absence of lymph nodes and Peyer's patches, and heterozygous (aly/+) mice. The small intestines were taken from 10 to 12-week-old mice and divided equally into 3 parts (the proximal, middle and distal parts). IELs were isolated from each part of the intestine and analyzed with a flow cytometer. The number of IELs in the distal part was significantly fewer in aly/aly mice compared with aly/+ mice, although the total number of small intestinal IELs were comparable between them. As to the IELs subsets, regional variations in alphabeta T cells and gammadelta T cells were observed in aly/+ mice, but they disappeared in aly/aly mice. However, regional variations in composition of alphabeta T cell subsets were similarly observed in both aly/aly mice and aly/+ mice. This indicates that, although not essential, mesenteric lymph nodes (MLN) and/or Peyer's patches may modify the regional variations in IELs. PMID- 11777283 TI - Nonlinear determinism in the immune system. In vivo influence of electromagnetic fields on different functions of murine lymphocyte subpopulations. AB - Animal studies of the effects of low-frequency electromagnetic fields (EMFs) on the immune system appear inconsistent, and recent evidence indicates that inconspicuous experimental problems are not responsible. We hypothesized that the inconsistencies resulted from use of linear methods and models to study inherently nonlinear input-output relationships. Using a novel analytical method, we found that exposure of mice to 5 G, 60 Hz, for 1-105 days in 6 independent experiments consistently affected a broad panel of immune variables when and only when the reaction of the immune system was modeled to allow the possibility of nonlinearity in the relationship between the field and the immune variables. It was possible to mimic the pattern observed in the immune data by sampling from a known chaotic system, suggesting the possibility that the observed pattern was the result of intrinsic nonlinear regulatory mechanisms in the immune system. Overall, the results suggested that lymphoid sub-populations were vulnerable to the physiological consequences of EMF transduction, that it may never be possible to predict specific changes in particular immune-system variables, and that the underlying behavior of the immune system (that which occurs in the absence of specific inputs) may be governed by laws that manifest extreme sensitivity to prior states. PMID- 11777284 TI - Antigenicity of poly(I) and ROS-poly(I) and their recognition of human anti-DNA autoantibodies. AB - The effect of hydroxyl radicals on polyinosinic acid [poly(I)] was studied. Strand breaks, base alteration and a decrease in absorbance at 248 nm (lambda max) were observed upon *OH modification of poly(I). The broad antigen specificity of the induced anti-poly(I) and anti-ROS-poly(I) antibodies showed diverse antigen binding characteristics similar to those of SLE autoantibodies. Recognition of both poly(I) and ROS-poly(I) by human SLE anti-DNA autoantibodies was observed. The possible significance of these findings in the etiology of SLE has been discussed. PMID- 11777285 TI - Secondary prevention of stroke: PROGRESS and the evidence for blood pressure reduction. PMID- 11777286 TI - MMR vaccine: combined or single antigens? PMID- 11777287 TI - Intrapleural urokinase in the management of parapneumonic empyema: a randomised controlled trial. AB - We compared the effectiveness of intrapleural urokinase versus normal saline via a thoracostomy tube in the treatment of parapneumonic empyema in a randomised controlled study. Forty-nine patients with parapneumonic empyema were randomly assigned to receive either intrapleural urokinase or normal saline treatment. The daily volume instilled through a chest tube was 100 ml in both groups. Urokinase (100,000 IU/day) was diluted in normal saline before instillation. The mean duration for defervescence was shorter (7 +/- 3 vs 13 +/- 5 days, p<0.01) and the mean volume of drained fluid during the five-day treatment period was significantly greater in the urokinase group (1.8 +/- 1.5 vs 0.8 +/- 0.8 litres, p<0.001) than in the control group. The subsequent decortication rate was 60% and 29.1%, respectively (p<0.001). The duration of hospitalisation was also shorter in the urokinase group (14 +/- 4 vs 21 +/- 4 days, p<0.001) than in the saline group. We conclude that intrapleural instillation of urokinase in the management of parapneumonic empyema provides a better outcome and reduces the need for decortication. PMID- 11777288 TI - Omeprazole versus ranitidine in the medical treatment of acute upper gastrointestinal bleeding: assessment by early repeat endoscopy. AB - The purpose of this study was to assess the effects of acid suppression in patients with upper gastrointestinal bleeding using early repeat endoscopy. Ninety-two patients with the diagnosis of acute upper gastrointestinal bleeding (endoscopically verified), entered a single-blind, randomised study comparing two treatment groups: omeprazole (40 mg orally daily) to ranitidine (50 mg intravenously four times daily). The lesions considered were gastric ulcers, duodenal ulcers and erosive gastritis. All patients were candidates for medical treatment. The parameters assessed included: 1) stabilisation of the lesion by repeat endoscopy at 7.0 +/- 3.0 days, 2) bleeding recurrence, 3) duration of stay in the intermediate medical care unit. For erosive gastritis only parameters 2 and 3 were considered. The study was limited to the hospitalisation period. Endoscopic stabilisation rate at 7.0 +/- 3.0 days for duodenal lesions was higher in the omeprazole group (71% vs 37%, p=0.03), but there was no significant difference for gastric lesions (50% vs 54%, NS). The overall bleeding recurrence rate (0% vs 17%, p=0.013) and the duration of stay (3.9 vs 6.4 days, p<0.01) were significantly lower in the omeprazole group. Our study suggests that omeprazole is more effective than ranitidine in the pharmacological treatment of acute upper gastrointestinal bleeding. PMID- 11777289 TI - A comparison of cardiovascular risk factors among Indo-Asian and caucasian patients admitted with acute myocardial infarction in Kuala Lumpur, Malaysia and Birmingham, England. AB - Indo-Asians in the UK are at an increased risk of coronary artery disease (CAD); this may be a reflection of their cardiovascular risk factor profile as well as of a more sedentary lifestyle. We hypothesised that Indo-Asians in Malaysia and the UK may exhibit a similar cardiovascular risk factor and physical activity profile, which would be more adverse compared with caucasians. We studied 70 consecutive Indo-Asian patients admitted to hospitals in Kuala Lumpur, Malaysia (n=42; 35 males; mean age 60.6 years, SD 11.8); and Birmingham, England (n=28; 20 males; mean age 60.8 years, SD 12.9). Both groups of Indo-Asian patients were compared with 20 caucasian patients (13 males; mean age 62.7 years, SD 9.4) admitted with myocardial infarction from Birmingham. There was a higher prevalence of diabetes among Indo-Asians in both countries than among caucasians (p=0.0225). By contrast, caucasians had a higher prevalence of hypercholesterolaemia (p=0.0113), peripheral vascular disease (p=0.0008), regular alcohol consumption (p<0.0001) and family history of CAD (p=0.0041). There were no significant differences in mean age, body mass index or blood pressures. There was a significantly lower leisure activity score (p=0.001) and total physical activity score (p=0.003) among Indo-Asians in both countries than among caucasians. This survey has demonstrated differences in cardiovascular risk factors among Indo-Asian and caucasian patients. The high prevalence of diabetes, as well as the lower physical activity and sedentary lifestyles among Indo Asians, in both Malaysia and the UK, may in part contribute to the high incidence of CAD in this ethnic group. PMID- 11777290 TI - Auditing first episode psychosis: giving meaning to clinical governance. AB - People in a first episode of psychosis are receiving increasing attention. This study describes the demographic and clinical diagnostic features of a cohort of 84 cases of first episode psychosis presenting in North Derbyshire from October 1999 to October 2000. Forty-two cases falling within the schizophrenia spectrum diagnosis were identified, an incidence rate of 0.17 per 1000 population. The rate for all psychoses, including drug-induced psychoses, was 0.35 per 1000 population aged 15-64. More than 50% of the cases were from the main urban centre, which contains around one third of the population. There were high rates of substance misuse in all diagnostic groups. The majority of patients (73%) presented via their general practitioners, but 18% presented via accident and emergency (13%) or the police (5%). The median duration of untreated psychosis for the whole group was two months. Within the schizophrenia spectrum group, however, there was a wide distribution, with duration of untreated psychosis of up to 10 years. The median duration of unteated psychosis in the schizophrenia spectrum group was three months. About half the cases in this cohort were aged more than 35 (all diagnostic categories). Further work exploring the outcome in this cohort is currently under way. As the configuration of mental health services is set to change rapidly in the next few years, there is a crucial need to develop further observational studies assessing how services deliver care to people with severe mental illness. PMID- 11777291 TI - Comparison of therapy with simvastatin 80 mg and 120 mg in patients with familial hypercholesterolaemia. AB - High-dose preparations of simvastatin and atorvastatin have recently become available to treat resistant hypercholesterolaemia aggressively, but few studies have compared these two agents. This study compared the efficacy of simvastatin 80 mg and 120 mg in 22 patients with severe familial hypercholesterolaemia over a three-month period using an open label format. Simvastatin 120 mg was reasonably well tolerated and delivered a further 8% reduction in LDL over 80 mg, giving a total reduction of 55 +/- 13%, while further decreasing triglycerides (18%) and continuing to raise HDL (13%) further than the 80 mg dose. However, transient adverse changes were noted in both lipoprotein (a) and fibrinogen and 20% of patients were unable to tolerate the higher dose. One late case of rhabdomyolysis was observed, suggesting patients on the 120 mg dose require continued regular review. PMID- 11777292 TI - 7. Management of advanced breast cancer. AB - Approximately half the patients with breast cancer relapse with locally recurrent or metastatic disease. This disease is incurable but can often be controlled, sometimes for many years. Careful clinical evaluation and restaging provides a baseline reference against which response can be judged. Investigations are selected but may include biochemical screens, blood counts, chest X-ray, isotopic bone scan and radiographs of abnormal regions. Selection of systemic treatment is based on three key factors: the extent, pattern and aggressiveness of the disease; hormone sensitivity; and menstrual status. Chemotherapy is used for rapidly progressing visceral disease such as lymphangitis carcinomatosa or hepatic metastases with deranged liver biochemistry where death ensues rapidly unless disease progression can be reversed. With less aggressive disease, treatment is planned around the oestrogen and progesterone status of the tumour. Those with low tumour receptor levels are unlikely to respond to endocrine treatment and chemotherapy should be considered. For patients with steroid receptor-positive tumours, endocrine treatment is used before chemotherapy is needed and consideration of menstrual status can assist in the selection of the precise approach. PMID- 11777293 TI - 8. The dilemma of in situ carcinoma of the breast. AB - Both ductal cardinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are forerunners of invasive breast cancer but with different behaviour. Neither condition is fatal but management can be difficult. After 20 years follow-up of LCIS, the cumulative risk of ipsilateral invasive cancer is 18%, and 14% for contralateral disease. Of the cancers that occur, 40% are invasive lobular and 60% invasive ductal. Standard management of LCIS is surveillance, with no attempt to perform a wide excision or a mastectomy. Many cases of DCIS are detected because of microcalcification on mammograms; 20% of screen-detected cancers are of this type. DCIS is a forerunner of ipsilateral invasive disease, so complete excision is necessary. Subsequent relapse or progression to invasive disease can be reduced by breast irradiation. Because of the extent of DCIS, a significant proportion of patients will need a total mastectomy with or without immediate reconstruction. PMID- 11777294 TI - Migraine: assessment and management. AB - Headaches occur at some time in the vast majority of the population. For most people headaches are a nuisance but for some they can be disabling. Two per cent of the population at any time have chronic daily headache, with or without analgesic dependence, but most disabling headaches are intermittent and migranous in nature. Before hoping to make an appropriate intervention, an accurate diagnosis must be made. The first part of this paper examines the differential diagnosis and in particular separates benign from sinister, acute from chronic and tension-type from migranous. The second half focuses on the management of migraine. An individualised approach is usually the most effective, with the patient drawing from the broad areas of attention to trigger factors and lifestyle, finding an acute or rescue medication that consistently returns them to normal activities within a few hours, and prophylaxis to reduce the rate of attack by 50% in those with high frequency migraine. The expession of migraine may well vary during an individual's life and in order to achieve the best lifelong control, adjustment of the blend of management options may be needed. The aim of the adviser is to enable patients to feel in control of their migraine rather than feeling that migraine controls them. PMID- 11777295 TI - Air travel and thrombosis. AB - It is now generally accepted that there is a link between long haul air travel and venous thromboembolism. A similar risk is also recognised with other modes of transport including long coach and car journeys, and the term 'traveller's thrombosis' is to be encouraged instead of 'economy class syndrome'. More research is required to quantify the precise risk, but the risk does appear to be small and largely confined to those with recognised risk factors, which include previous episode of thrombosis, hormonal therapy, recent surgery, malignancy and pregnancy. In addition, haematological abnormalities can predispose to thrombosis. Such thrombophilic disorders include the factor V Leiden mutation and deficiencies of natural anticoagulants such as antithrombin, protein C and protein S. General measures which can be taken to reduce the risk include leg exercises while seated. In addition, there is evidence to support the use of elasticated stockings, but evidence relating to the use of aspirin is less convincing. PMID- 11777297 TI - A case of percutaneous balloon mitral valvuloplasty for severe symptomatic mitral stenosis in an octogenarian. AB - Compared with mitral valve replacement as treatment for severe mitral stenosis, balloon mitral valvuloplasty (BMV) is a less invasive and well-established alternative therapeutic procedure. The best results are obtained with BMV in association with pliable, non-calcified valves. However, in the western world, mitral stenosis is predominantly a condition of the elderly, in whom less favourable valve anatomy is generally found. In this report we describe the case of an 86-year-old woman with severe symptomatic mitral stenosis and breathlessness on minimal exertion who underwent successful BMV. Following the procedure she was able to function independently. This serves to highlight the fact that BMV should be considered in the treatment of symptomatic mitral stenosis, irrespective of age. PMID- 11777296 TI - Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes. AB - This meta-analysis of published studies evaluated the effect of selective alpha1 blockers on lipid and carbohydrate profiles and blood pressure (BP) as well as tolerability in patients with hypertension and type 2 diabetes. Publications identified via MEDLINE were used. Text and bibliographies of retrieved articles were examined for additional references. Clinical trials with a randomised comparative structure (placebo and active treatment arms) and controlled studies with other structures were included. Of the 27 citations identified, 22 studies were selected for inclusion, and five were rejected. Efficacy and safety data, lipid and carbohydrate profiles, and study and patient characteristics were extracted by two investigators independently. The mean pooled results showed beneficial effects of selective alpha1-blockers on total serum cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and systolic and diastolic BP. The results also showed doxazosin had beneficial effects on fasting glucose levels, insulin sensitivity, TC, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, HDL/TC ratio, and systolic and diastolic BP. The risk difference was equivalent between the alpha1-blocker group and the control group for postural hypotension or syncope. This meta-analysis demonstrates a number of favourable effects of therapy with selective alpha1-blockers in hypertensive patients with type 2 diabetes. These agents provide an effective modality for reducing BP, with favourable effects on lipid, no deterioration in glycaemic control, and little risk of orthostatic hypotension. PMID- 11777298 TI - The potential place of tenofovir in antiretroviral treatment regimens. AB - Advice from the Food & Drug Administration and the European Medicines Commission indicates that tenofovir is likely to be licensed shortly for use in patients failing antiretroviral therapy as part of a regimen constructed by the clinician. Tenofovir is a nucleotide (NtRTI) that acts in a similar way to nucleoside analogues by inhibiting reverse transcriptase, producing similar HIV plasma viral load fall. In use up to 48 weeks it appears to be safe without evident toxicity. It has particular value because it has activity against many HIV viruses with mutations which render them insensitive to other nucleoside analogues. Its eventual optimal role in treatment, particularly whether it should be part of a first line regimen, awaits the outcome of further studies. PMID- 11777299 TI - Cholesterol absorption inhibition: a strategy for cholesterol-lowering therapy. AB - A clear relationship has been documented between plasma levels of low-density lipoprotein cholesterol (LDL-C) and the risk of coronary heart disease. LDL-C is believed to be key in the pathogenesis of coronary atherosclerosis, although increasing evidence suggests that low levels of high-density lipoprotein cholesterol and elevated triglyceride levels are contributory factors. Chylomicron remnants formed via the exogenous (dietary and biliary) pathway of cholesterol metabolism may also have atherogenic potential. Dietary modification, especially with plant stanol (sterol) ester margarine, which inhibits cholesterol absorption and improves the fatty acid pattern, lowers LDL-C sufficiently in many hypercholesterolaemic patients, and is also a useful adjunct to pharmacological therapy. Cholesterol absorption inhibitors typically lower LDL-C by 10-20%. Ezetimibe, the first selective cholesterol absorption inhibitor, has been shown to lower LDL-C by approximately 18% following a once-daily 10 mg dose, either as monotherapy or as combination therapy. Combination therapy with selective cholesterol absorption inhibitors such as ezetimibe along with statins or fibrates may allow more patients with hypercholesterolaemia to achieve target LDL C levels compared with treatment with monotherapy. Ezetimibe may be useful in the management of patients who respond poorly to or are unable to tolerate statins, or in patients with hereditary or drug-induced phytosterolaemia. PMID- 11777300 TI - Inflammatory pseudotumour of the liver associated with diabetes mellitus. AB - Inflammatory pseudotumours of the liver are rare benign tumours of unknown origin, usually mistaken for malignant lesions. Two patients with Type 2 diabetes presented separately, unwell with fever, weight loss and hepatomegaly. Ultrasonography revealed 3-4 cm multiple lesions in the liver of the first case and a solitary 5 cm mass in the right lobe of the liver in the second. Biopsies revealed inflammatory pseudotumours in both cases. Both patients were treated with intravenous antibiotics and fluids. The clinical outcome was good and both patients had an uneventful recovery. We believe these to be the first two cases of inflammatory liver pseudotumours to be described in patients with diabetes mellitus. PMID- 11777301 TI - Spontaneous coronary artery spasm during coronary angiography in a patient with exercise-induced ST segment elevation. AB - We describe a patient with a history of early morning chest pain who developed ST segment elevation during a treadmill exercise test. Severe coronary artery stenosis was identified initially and was relieved after intracoronary administration of nitroglycerin. A history of vasospastic angina in this patient facilitated prompt diagnosis. PMID- 11777302 TI - Massive scrotal haematoma: a complication of percutaneous transluminal angioplasty. AB - Scrotal haematoma is an unusual complication following percutaneous transluminal angioplasty. It carries significant morbidity and causes extreme discomfort to the patient. We describe the case of a 75-year-old diabetic man who developed this complication. Recommendations are made for investigation and management of this problem, which is so infrequently encountered in clinical practice. PMID- 11777303 TI - Sausage asphyxia. AB - A foreign body causing obstruction of the larynx is usually removed by coughing, blows to the back, chest thrusts, abdominal compression or finger sweep manoeuvres on the unconscious victim. In extremis, crichothyroidotomy or emergency tracheostomy may be the only life-saving option. Direct laryngoscopy may permit the removal of a foreign body from the larynx of an unconscious victim. Problems arise if the victim is semiconscious and not able to tolerate instruments in the mouth without sedative medication, which might result in the inhalation of the foreign body. A case of supraglottic impaction of the larynx by a piece of sausage occurred in our hospital; the patient was semiconscious. It was managed successfully by a carefully timed laryngoscope blade being inserted into the mouth without the aid of sedative drugs. PMID- 11777304 TI - True aneurysm of a femoropopliteal vein graft. AB - Aneurysmal dilatation of saphenous vein grafts mostly represent thin-walled pseudoaneurysms at anastomotic sites. True aneurysmal dilatation of femoropopliteal bypass vein grafts is rare. We report this unusual case, which was repaired with a prosthetic graft. PMID- 11777305 TI - Neonatal amniotic fluid aspiration syndrome underdiagnosed? AB - Aspiration of uncontaminated amniotic fluid as a cause of significant respiratory distress in neonates is not well documented. We report a term neonate who presented with severe respiratory distress soon after birth. The diagnosis of amniotic fluid aspiration was confirmed at autopsy. Implications of this diagnosis in the management of neonates with respiratory distress are discussed. PMID- 11777306 TI - Life-threatening haemoptysis presenting as a late complication of an ovarian tumour. AB - Massive haemoptysis may arise as a result of lung malignancy. This case represents the first report of an ovarian granulosa cell tumour metastasising many years after initial tumour resection to the lung causing life-threatening haemoptysis. The management and subsequent clinical course of the patient are discussed as well as the natural history of granulosa-theca cell tumours. PMID- 11777307 TI - Gastric lipoma causing gastroduodenal intussusception. AB - A case of gastroduodenal intussusception caused by a submucosal gastric lipoma in a 48-year-old man is presented. He had intermittent symptoms of regurgitation and heartburn for a period of three years. Barium meal and CT scan showed a mass in the first part of duodenum. At laparotomy there was intussusception of gastric antrum into the duodenum with a submucosal lipoma in the antrum which formed the apex of the intussusception. PMID- 11777308 TI - Analysis of the information content in Sonoclot data and reconstruction of coagulation test variables. AB - The Sonoclot Coagulation Analyzer is a viscoelastometer used for in vitro analysis of the coagulation process from the start of fibrin formation, through polymerization of the fibrin monomer, platelet interaction, and eventually to clot retraction and lysis. In this paper, we have analyzed series of Sonoclot curves and simultaneously obtained coagulation tests (APT, PT, Fibrinogen, Platelet Count, and D-dimer) from patients who underwent total hip replacements (THA). By using the Principal Component Analysis method (PCA), we found that the most important coagulation test variables as reflected in the Sonoclot signature, are Platelet Count, PT, and Fibrinogen. Also, by using a Back-Propagation Neural Network (BP), we were able to reconstruct the coagulation variables Platelet Count, PT, and Fibrinogen from the Sonoclot curve with a reasonable accuracy. This would also indicate that these three coagulation test variables are most important in determining the appearance of the Sonoclot signature. PMID- 11777309 TI - Cardiovascular interactions tutorial: architecture and design. AB - This work examines the design and architecture of a delivery system for a computerized, interactive tutorial on the physiology of the cardiovascular system. Emphasis in this paper is on the mechanisms used to coordinate the user's Lab Workbook, subject-oriented Information file, and the cardiovascular interaction (CVI) simulation model. Techniques described are sufficiently generic to allow for different tutorial content and/or different simulation models. Implementation uses Visual Basic and deployment is CDROM-based. PMID- 11777310 TI - Measurement of technical efficiency of public hospitals in Kenya: using Data Envelopment Analysis. AB - In Sub-Saharan Africa (SSA), there is a huge knowledge gap of health facilities performance. The objective of this study is to measure relative technical efficiencies of 54 public hospitals in Kenya using Data Envelopment Analysis (DEA) technique. 14 (26%) of the public hospitals were found to be technically inefficient. The study singled out the inefficient hospitals and provided the magnitudes of specific input reductions or output increases needed to attain technical efficiency. PMID- 11777311 TI - Clictate: a computer-based documentation tool for guideline-based care. AB - The use of computer-based documentation tools confers many benefits to the delivery of evidence-based health care. We developed Clictate, a structured reporting environment that utilized standard Windows-based data entry constructs and natural language generation. Clictate has been in use for over 3 years by pediatric providers in an ambulatory setting. More than 50% of our providers use Clictate during the patient encounter. This report describes our results to date, and suggests future opportunities for research and development in the area of computer-based documentation. PMID- 11777312 TI - A practical procedure to prevent electromagnetic interference with electronic medical equipment. AB - Problems involving electromagnetic interference (EMI) with electronic medical equipment are well-documented. However, no systematic investigation of EMI has been done. We have systematically investigated the causes of EMI. The factors involved in EMI were determined as follows: 1) Electric-field intensity induced by invasive radio waves from outside a hospital. 2) Residual magnetic-flux density at welding points in a building. 3) Electric-field intensity induced by conveyance systems with a linear motor. 4) The shielding capacity of hospital walls. 5) The shielding capacity of commercial shields against a wide range frequency radio waves. 6) The immunity of electronic medical equipment. 7) EMI by cellular telephone and personal handy-phone system handsets. From the results of our investigation, we developed a following practical procedure to prevent EMI. 1) Measurement of electric-field intensity induced by invasive radio waves from outside the hospital and industrial systems in the hospital. 2) Measurement of residual magnetic-flux density at electric welding points of hospital buildings with steel frame structures. 3) Control of the electromagnetic environment by utilizing the shielding capacity of walls. 4) Measurement of the immunity of electronic medical equipment. And 5) Installation of electronic gate equipment at the building entrance to screen for handsets. PMID- 11777313 TI - On-site investigation of the early phase of Bhutan Health Telematics Project. AB - Telemedicine is valuable to many developing countries. International use of telemedicine is widespread. Telemedicine can improve health care in the developing countries by removing time and distance barrier, and optimize the use of limited health services in developing countries. The purpose of this paper is to investigate the current situation of healthcare services and telecommunications infrastructure in Bhutan. It summarizes the experience gained from a previous telemedicine pilot project initiated and implemented by the Telecommunication Development Bureau, International Telecommunication Union (BDT/ITU). It also introduces the priorities of telemedicine development set out by the local health authorities as well as the international organizations. By analyzing the common and most urgent problems in the country, which could be alleviated by using telemedicine, it formulates several recommendations concerning the future development strategy of telemedicine in Bhutan. PMID- 11777314 TI - Simulation analysis of pneumatic tube systems. AB - Pneumatic tube systems play an important material handling role in many hospitals. These systems are costly and complex to design and operate, yet little exists in the way of analytical methodologies for them. We present a decision support framework based on defining relevant system performance metrics, traffic analysis reporting, as well as discrete event simulation modeling. We have used this approach to analyze numerous pneumatic tubes systems in the United States and present a representative case study from a large tertiary care hospital. Our general approach can be generalized to other computer controlled hospital operational systems such as elevators, track vehicles, automatic guided vehicles, workflow enabled processes, and laboratory automation systems. PMID- 11777315 TI - Effect of pentoxifylline on ischemic acute renal failure in rabbits. AB - Previous studies have demonstrated that levels of tumor necrosis factor-alpha (TNF-alpha) or its mRNA expression are increased in acute renal failure of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-alpha production, provides a protective effect against ischemic acute renal failure in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with PTX (30 mg/kg, i.v.) 10 min before release of clamp. At 24 h of reperfusion of blood after ischemia, changes in renal function, renal blood flow, and the expression of TNF-alpha mRNA were evaluated. Ischemia/reperfusion caused a marked reduction in GFR, which was accompanied by an increase of serum creatinine levels. Such changes were significantly attenuated by PTX pretreatment. PTX ameliorated the impairment of renal tubular function, but it had no effect on the reduction of renal blood flow induced by ischemia/reperfusion. The protective effect of PTX on functional changes was supported by morphological studies. The impairment of glucose and phosphate reabsorption in postischemic kidneys was associated with a depression in the expression of Na+-glucose and Na+-Pi transporters. The expression of TNF-alpha mRNA was increased after reperfusion, which was inhibited by PTX pretreatment. The PTX pretreatment in vitro prevented the release of lactate dehydrogenase induced by an oxidant t-butylhydroperoxide in rabbit renal cortical slices, but it did not produce any effect on the oxidant-induced lipid peroxidation, suggesting that PTX protection is not resulted from its antioxidant action. These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-alpha in rabbits. PMID- 11777316 TI - Early administration of PDTC in adriamycin nephropathy: effect on proteinuria, cortical tubulointerstitial injury, and NF-kappaB activation. AB - The persistence of NF-kappaB independent inflammatory signals in the cortical tubulointerstitium may explain the incomplete suppression of interstitial monocyte accumulation by the antioxidant NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), in nephrotic rats with established Adriamycin nephropathy (AN). Because PDTC is known to have anti-proteinuric effects, in this study we investigated whether earlier commencement, during the pre-nephrotic phase of AN, would be more effective in reducing interstitial monocyte accumulation. Male Wistar rats with AN received either vehicle or PDTC (50 mg/kg bd i.p.i.) from d7 until d30 (n = 8 per group). On d30, PDTC reduced renal cortical lipid peroxidation (43%), wet kidney weight and tubulointerstitial injury in AN, but did not decrease proteinuria. Accordingly, inhibition of interstitial ED-1 accumulation remained incomplete (52%). Interestingly, the early administration of PDTC in AN, induced polyuria and renal cortical NF-kappaB DNA-binding activity was reduced by only 35%. These results suggest that: (i) the combination of an anti-proteinuric agent with PDTC may be required to completely suppress interstitial monocyte cell accumulation in AN and, (ii) the timing and duration of PDTC therapy are an important determinant of its efficacy to reduce NF-kappaB activation, in vivo. PMID- 11777317 TI - Recognition of neurocognitive dysfunction in chronic hemodialysis patients. AB - We sought to determine the prevalence, recognition, and consequences of mental impairment among chronic hemodialysis patients. We administered the Mini Mental Status Exam (MMSE), a brief validated method for assessing cognitive mental status that is commonly used by clinicians, to 84 patients from our dialysis units. To determine the clinical implications of mental impairment, we obtained Kt/V, albumin, protein catabolic rate, blood pressure, and hematocrit values. We found that 21% of subjects had mild mental impairment (MMSE 18 to 23) and that 11% had moderate-severe mental impairment (MMSE 0 to 17). We found no relationship between MMSE score and years on dialysis, Kt/V value, hematocrit value, or erythropoietin use. On univariate analysis, MMSE score was associated with albumin, protein catabolic rate, inter-dialytic weight gain, number of co morbid conditions, number of hospitalizations. Outcomes on univariate analysis were further analyzed by multivariate analysis. There was an independent relationship between decrement in MMSE score and lower protein catabolic rate and increased hospitalization number and number of co-morbid conditions. Based on our findings, we recommend that clinicians routinely screen hemodialysis patients for mental impairment and target impaired patients for interventions to improve mental status and associated adverse outcomes. PMID- 11777319 TI - Predictors of coronary disease in patients with end stage renal disease. AB - Patients with end stage renal disease have a high prevalence of cardiovascular disease and coronary arteriography is often routinely performed prior to kidney transplantation. However, the value of the conventional risk factors and non invasive markers of coronary artery disease (CAD) in triaging patients for coronary arteriography has not been fully examined. 116 patients with end stage renal disease were evaluated. Coronary arteriography was performed in all patients either for a suspicion of CAD or as part of a routine pre-transplant evaluation. Lesions causing > or = 50% luminal diameter stenosis in any of the three major coronary artery systems were considered significant. The mean age was 53.3 +/- 9.3 years. Significant CAD was present in 69 patients (60%). Increasing age, family history of premature ischemic heart disease, the presence of angina, abnormal Q waves on the ECG or abnormal ST segment depression and the presence of coronary calcification were significant markers of coronary artery disease. However male gender, diabetes mellitus and obesity did not correlate with coronary disease. Even though hypertension, hypercholesterolemia and smoking were also not useful predictors these could have been modified by the renal failure. In conclusion increasing age, a family history of premature ischemic heart disease and some non-invasive markers were useful predictors of coronary disease. PMID- 11777318 TI - The effect of an iron supplement on serum aluminum level and desferrioxamine mobilization test in hemodialysis patients. AB - BACKGROUND: The serum aluminum (Al) measurement with desferrioxamine (DFO) mobilization is a screening test for uremic patients with an Al overload. In these patients, body iron status is one of the factors affecting the serum Al level. This study is designed to elucidate the effects of iron supplements on the serum Al and the DFO mobilization test. METHODS: Our study featured ten hemodialysis patients with iron deficiency anemia. The iron supplement was given intravenously with saccharated ferric oxide, 40 mg three times weekly, at the end of each hemodialysis. The total amount of iron supplement was 1,000 mg. All the patients underwent a DFO test at a dose of 5 mg/kg. The same test was repeated two weeks after completion of the iron supplement. RESULTS: After the iron supplement, patients' iron deficiency anemia improved with a serum ferritin elevation from 312.4 +/- 589.5 to 748.2 +/- 566.2 microg/L (p < 0.01), and iron saturation from 21.6 +/- 20.3 to 41.1 +/- 21.7% (p = 0.06). The basal serum Al level decreased from 34.3 +/- 13.8 to 21.8 +/- 8.5 microg/L (p = 0.01). In the DFO mobilization test, the peak serum Al level decreased from 63.4 +/- 19.3 to 50.7 +/- 20.5 microg/L (p < 0.01). The amount of Al increment (deltaAl) in DFO test was not changed (29.1 +/- 12.0 vs. 28.9 +/- 15.9 microg/L, p = 0.86). The change in basal Al level tended to negatively correlate with the percentage of increment in iron saturation (r = -0.628, p = 0.05). CONCLUSION: Results in this study suggest that iron supplements may significantly reduce the basal serum Al and peak Al in DFO mobilization test, without significant change of the mean deltaAl. The data presented indicate that in the interpretation of serum aluminum levels the iron status should be taken into account. PMID- 11777320 TI - Spectrum of liver damage and correlation with clinical and laboratory parameters in HCV infected hemodialysis patients. AB - There are conflicting results in studies concerning the best marker for liver histopathological features of HCV infection in HD patients. We planned a prospective study to follow HCV viremia and laboratory parameters of HD patients and correlate these with clinic features and histopathological findings. We included 68 HCV infected patients (45 male, 23 female, age: 39.8 +/- 11.9 years, HD duration: 58.2 +/- 36.4 months) in our study. The follow-up period after the biopsy was 33.2 +/- 20.3 months. Patients liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT)) levels were determined monthly and ferritin levels every three months, and the mean value was recorded. We also screened patients for HCV RNA. During the follow-up period, 22 (32.4%) of the patients had positive RNA, 26 (38.2%) negative RNA. 20 (29.4%) had intermittent RNA positivity. The patients with high grade of portal necroinflammatory activity had significantly higher AST and ALT levels. In addition patients with high grade lobular activity had significantly shorter HD and HCV infection duration and higher AST, ALT and ferritin levels. AST levels were negatively correlated with duration of HD and HCV infection, and positively correlated with GGT and ferritin levels. Additionally, we found that ALT levels were negatively correlated with HD duration and positively correlated with GGT levels. ALT levels higher than 30 U/L were reflected necroinflammatory activity more significantly than levels higher than 40 U/L. Cirrhosis was detected in 5.9% of the patients, and we could not find any laboratory parameter that was correlated with stage of fibrosis. Although there is a high degree of liver involvement, cirrhosis is a relatively less frequent finding in HD patients. Serum aminotransferases and ferritin levels but not the pattern of HCV viremia are predictors of necroinflammatory activity in liver biopsy specimens. Liver biopsy obligatory to assess the disease activity in HD patients. PMID- 11777321 TI - Warning of high-flux hemodialysis. AB - In order to estimate the influence of flux on plasma refilling during hemodialysis (HD), prospective crossover studies were performed in 10 HD patients with low-flux and high-flux dialyzers. Hematocrit was continuously monitored to assess changes in blood volume. In addition, plasma osmolarity and total protein concentration were measured. Intradialytic reductions in body weight (-5 +/- 1 vs -5 +/- 1%) and plasma osmolarity (-5 +/- 1 vs -5 +/- 1%) were similar in both conditions. Although mean blood pressure remained unchanged in either state, the decrease in blood volume was larger in high-flux HD (-13 +/- 2 vs -10 +/- 2%, p<0.05). In spite of greater contraction in blood volume during high-flux HD, total proteins were increased equally between low-flux and high-flux HD (11 +/- 4 vs 11 +/- 4%). Our data that although high-flux HD failed to induce significant drops in blood pressure, it elicited greater magnitude of decreases in blood volume, implicate the judicious application of high-flux HD. PMID- 11777322 TI - Neglected bilateral femoral neck fractures in a patient with end-stage renal disease before chronic dialysis. AB - Bilateral femoral neck fractures are rarely reported in patients with end-stage renal disease before chronic dialysis. We report on a 39-year-old woman with neglected bilateral femoral neck fractures, who presented with severe uremic complications prior to chronic dialysis. Three years before admission, she had injured herself in a trivial slip with subsequent bilateral hip pain. She had progressively waddled since then. Pelvic X-ray taken after admission revealed bilateral femoral neck fractures. Bilateral hip hemiarthroplasties were subsequently performed. Displaced femoral neck fractures were found intraoperatively. Pathologic findings and results of examinations supported the coexistence of osteoporosis and high turnover renal osteodystrophy, rendering this woman at high risk of bilateral femoral neck fractures. Therefore, preventing a simple fall or trivial accident and treating renal osteodystrophy and osteoporosis are paramount in patients with chronic renal failure even before the start of dialysis therapy. We also emphasize the need to seek any possible underlying metabolic bone disease once a patient presents with unusual fractures. PMID- 11777323 TI - Insulin and mineralocorticoids influence on extrarenal potassium metabolism in chronic hemodialysis patients. AB - Insulin-mineral corticoids effects on extrarenal K+ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K+ over the past 12 months: > 6.0 mEq/L (G1, n=5), = 5.1-6.0 mEq/L (G2, n=5), < or = 5.0 mEq/L (G3, n=5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO3-, glucose, body weight, blood pressure and heart rate were measured before and 60' after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1-T3); G1 received fluorohydrocortisone (FHC) 0.1 mg-0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 +/- 23 to 157 +/- 52 mg/dL, P<0.001) and insulin (11.8 +/- 6.2 to 46.8 +/- 19.5 microU/mL, P<0.001), with a drop in K+ (5.1 +/- 0.6 to 4.8 +/- 0.7 mEq/L, P=0.001) and aldosterone (453 +/- 373 to 383 +/- 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r= 0.54, P<0.04) to serum K+ at T60, in all patients. (B) No major pH, HCO3 and aldosterone changes were observed in the 3 groups. Despite that, K+ dropped in G1 by FHC (6.7 +/- 0.9 to 5.9 +/- 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 +/- 0.4 to 5.4 +/- 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 +/- 0.2 to 5.8 +/- 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K+ by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K+ handling in steady state anuric dialysis patients. PMID- 11777324 TI - Acute effect of hemodialysis on sympathetic skin response. AB - Sympathetic skin response (SSR) is a useful and simple test for unmyelinated axon function in peripheral sensorimotor neuropathies. SSR was tested on a group of patients undergoing chronic regular hemodialysis before and after a single dialysis session. Nineteen patients in hemodialysis for more than three months were included. Nine patients were on dialysis with cellulosic membranes (CA, 3 male and 6 female, aged 57.7 +/- 16.4 years) and ten ones were on dialysis with non-cellulosic membranes (NC, 4 male and 6 female, aged 50.2 +/- 15.9 years) were studied. There were no differences neither in Kt/V values (NC 1.37 +/- 0.34 vs. CA 1.22 +/- 0.27) nor in TAC ones (NC 41.5 +/- 18.2 vs. CA 41.3 +/- 14.1 mg/dL). After hemodialysis with NC amplitude significantly increased (994 +/- 1015 vs. 382 +/- 465 microv baseline, p < 0.05). Latency did not change (1.76 +/- 0.83 vs. 2.07 +/- 0.50 s baseline). After hemodialysis with CA neither amplitude changed (1368 +/- 1074 vs. 1240 +/- 1594 microv baseline), nor did latency (1.79 +/- 0.35 vs. 1.94 +/- 0.59 s baseline). Hemodialysis with non-cellulosic membranes (but not with cellulose acetate) yields a short-term improvement of sympathetic skin response. This effect is similar to those seen in nerve conduction velocities and it may be related to increased middle-molecules depuration. PMID- 11777325 TI - Ticlopidine-induced thrombotic thrombocytopenic purpura: two case reports treated with plasma exchange plus steroids. AB - Thrombotic thrombocytopenic purpura (TTP) has a high mortality rate if left untreated with plasma exchange promptly. We report two cases of ticlopidine induced TTP, which lesser dosages of ticlopidine (200-250 mg/day) were prescribed and were treated with plasma exchange (PE) plus steroids. The first case was treated successfully, but the second case did not respond to our treatment and died of a progressive disease complicated with pneumonia. In sum, we recommend careful use of ticlopidine, regardless of the dosages prescribe and regardless of how long the drug is used. Moreover, the adverse effect of ticlopidine should be closely monitored. PMID- 11777326 TI - Use of gadolinium-based contrast agent for renal angiography: case report and review of the literature. AB - A 67-year-old woman suffering from chronic renal failure (Creatinine 480 micromol/L) underwent a gadolinium renal angiography, which visualized a stenosis of the right renal artery. There was no deterioration of renal function after the arteriography. A review of the literature is presented which show the efficiency of this technique to visualize the renal arteries, and the absence of nephrotoxicity after the use of gadolinium as a based contrast agent in high risk patients. PMID- 11777327 TI - Effect of pioglitazone on dyslipidemia in hemodialysis patients with type 2 diabetes. PMID- 11777328 TI - Assessing children's responses to terrorism. PMID- 11777329 TI - Childrens' and adolescents' use of diaries for sickle cell pain. AB - ISSUES AND PURPOSE: To evaluate the characteristics of vaso-occlusive episodes, home management of pain and its impact on the daily activities, and a diary as a method of data collection. DESIGN AND METHODS: Forty-six adolescents and 75 children were asked to complete daily diaries during the intervention period of a larger study. RESULTS: Mild pain was recorded 95% of the time; moderate pain, 3%; and severe pain, 1%. The pattern and location of pain varied greatly. Adolescents used more interventions than did children. When pain intensity was mild, 80% of the children/adolescents maintained school, social, and home activities, but decreased play/sport activities. When pain intensity was high, they decreased their participation in all activities. PRACTICE IMPLICATIONS: Sickle cell pain episodes are unpredictable and highly variable. Diaries can enhance children's and adolescents' documentation and communication about their pain experiences. PMID- 11777330 TI - Child care health consultation: an ecological model. AB - ISSUES AND PURPOSE: To present an ecological model of child care health consultation that defines the role of the health consultant as a resource and advocate within child care programs, as well as a supportive link among families, child care providers, and the healthcare system. CONCLUSIONS: Nurses have provided health consultation to child care programs for more than 30 years and represent the majority of health consultants nationally. Pediatric nurses and advanced practice nurses are well prepared to shape and lead the development of this emerging role. PRACTICE IMPLICATIONS: With expertise in caring for children, understanding families, and care across systems, pediatric nurses and advanced practice nurses should engage in current state and national efforts to develop child care health consultants. PMID- 11777331 TI - The use of dexamethasone in the prevention of postextubation stridor in pediatric patients in PICU/NICU settings: an analytical review. AB - ISSUES AND PURPOSE: Dexamethasone has been used to prevent postextubation stridor in children, but its use is controversial. Five randomized, controlled clinical trials were reviewed to analyze the effectiveness of prophylactic dexamethasone on postextubation stridor in pediatric patients. CONCLUSIONS: Previous studies had inconsistent results. Several factors may contribute to postextubation stridor in pediatric patients. Postextubation stridor and extubation failure do not always result from airway edema. PRACTICE IMPLICATIONS: In addition to prophylactic dexamethasone, other approaches should be used to prevent postextubation stridor, such as preparing the patient, following established guidelines, and providing appropriate postextubation care. PMID- 11777332 TI - Taking a temperature: which way is best? PMID- 11777333 TI - Abby's gift. PMID- 11777334 TI - Cancer cell motility--on the road from c-erbB-2 receptor steered signaling to actin reorganization. AB - Cell migration depends mainly on actin polymerization and intracellular organization, which are influenced by a vast variety of actin binding proteins (ABPs). Regulation of ABP activity is mediated by second messengers such as phosphoinositides and calcium. Signaling via these second messengers is initiated and regulated by membrane receptors, e.g., receptor tyrosine kinases (RTKs), and by adhesion molecule interactions (e.g., integrins and selectins) and focal adhesion kinases. A major role in steering second-messenger signaling and thus in actin cytoskeleton reorganization and motility of cancer cells is played by the RTK c-erbB-2. This occurs through a number of signaling pathways which involve mainly enzymes, e.g., phospholipase Cgamma1 and GTPases, which modify signaling molecules. Furthermore large multiprotein complexes including actin-related protein 2/3, Wiskott-Aldrich syndrome protein, profilin, and capping protein among others play an important role in regulating actin reorganization. The complex picture of the mode of actin reorganization, which is involved in tumor cell migration, is slowly emerging from the mists of cellular signaling pathways, but this is still by no means a clear view. PMID- 11777335 TI - MT1-MMP-dependent and -independent regulation of gelatinase A activation in long term, ascorbate-treated fibroblast cultures: regulation by fibrillar collagen. AB - Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen alpha1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length alpha1(I) collagen cDNA, and to our surprise, also by transfection with an alpha1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1 MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes. PMID- 11777336 TI - Thymic epithelial cells mediate a Bcl-2-independent protection of single-positive thymocytes from dexamethasone-induced apoptosis. AB - Intrathymic maturation of thymocytes is essential for the proper formation of T cell repertoire. This process involves two major biochemical pathways, one initiated by the recognition of MHC/peptide by the T-cell receptor and the other mediated by glucocorticoids. These hormones seem to affect thymocyte maturation by increasing the threshold of TCR-mediated positive and negative selection, and by inducing apoptosis of nonselected thymocytes. We have previously reported that an SV40-immortalized murine thymic epithelial cell line, namely 2BH4, was able to protect thymocytes from dexamethasone-induced apoptosis. Here we show that this protection is independent of cell-to-cell contact and does not seem to involve a Bcl-2-mediated resistance, since incubation of thymocytes with 2BH4 cells or its supernatant does not interfere with the levels of this antiapoptotic molecule. The protection conferred by 2BH4 cells, or by a primary culture of thymic stromal cells, is specific for the CD4(+)CD8(-) and CD4(-)CD8(+) single-positive thymocytes, whereas the broad-spectrum caspase inhibitor z-VAD-fmk blocks apoptosis induced by dexamethasone in all thymocyte subpopulations. Our results suggest that positively selected single-positive thymocytes are still susceptible to glucocorticoid-induced apoptosis but are protected from it through the action of a heat-stable protein(s) released by thymic stromal cells. PMID- 11777337 TI - Microfilament disruption in a noncycling organized tissue, the corneal endothelium, initiates mitosis. AB - The adult corneal endothelium represents a noncycling cell population that resides as a monolayer on its basement membrane, Descemet's membrane. Evidence is presented for the first time, showing that mitotic regulation in this organized tissue, residing on its natural basement membrane, is coupled to microfilament integrity. When mitotically quiescent rat corneal endothelia are organ cultured in medium containing serum and cytochalasin B, low levels of mitosis are initiated. Supplementing the culture medium with either insulin or IGF-2 augments this response and results in increased cell density within the tissue monolayer. Fluorescence microscopy of actin using TRITC-conjugated phalloidin revealed that cellular circumferential microfilament bundles appear unaffected by cytochalasin B treatment, whereas the cytoplasmic microfilaments appear to be completely disrupted. These results suggest the possibility that the actin cytoskeleton is involved with the regulation of cell growth in the corneal endothelium. PMID- 11777338 TI - Differential localization of chicken FIP2 homologue, Ag-9C5, in secretory epithelial cells. AB - When hepatocytes polarize, a subset of cellular proteins specifically localizes to the apical cell surface forming the boundary of the bile canaliculus. We have isolated a cDNA encoding a protein recognized by a monoclonal antibody (9C5) that specifically stains the bile canaliculus. The encoded protein (Ag-9C5) is a cytoplasmic protein with three leucine zippers and a zinc finger at the C terminus. Extensive amino acid sequence similarity indicates that Ag-9C5 is likely the chicken homologue of a human protein, FIP2, which interacts with huntingtin and Rab8. Epitope-tagged Ag-9C5 colocalizes with endogenous Ag-9C5 and other canaliculus marker antigens in transfected organ cultures. In Cos7 cells and MDCK cells Ag-9C5 forms punctate cytoplasmic structures. In intact tissues Ag 9C5 is highly concentrated at the apical surfaces of cells that secrete protein from the apical surfaces, but is found in a fine punctate cytoplasmic pattern in other polarized epithelia. Because this protein has a number of characteristics of proteins that act as scaffolds for assembly of protein complexes (e.g., the cytoplasmic domain of classical cadherins and the FERM superfamily of proteins), it appears that FIP2/Ag-9C5 may act as a scaffold for assembling a complex of proteins that are involved in targeting of some secretory vesicles to defined regions of the cell surface. PMID- 11777339 TI - Telomere biology and cellular aging in nonhuman primate cells. AB - To determine how cellular aging is conserved among primates, we analyzed the replicative potential and telomere shortening in skin fibroblasts of anthropoids and prosimians. The average telomere length of the New World primates Ateles geoffroyi (spider monkey) and Saimiri sciureus (squirrel monkey) and the Old World primates Macaca mulatta (rhesus monkey), Pongo pygmaeus (orangutan), and Pan paniscus (pigmy chimpanzee) ranged from 4 to 16 kb. We found that telomere shortening limits the replicative capacity of anthropoid fibroblasts and that the expression of human telomerase produced telomere elongation and the extension of their in vitro life span. In contrast the prosimian Lemur catta (ring-tailed lemur) had both long and short telomeres and telomere shortening did not provide an absolute barrier to immortalization. Following a transient growth arrest a subset of cells showing a reduced number of chromosomes overgrew the cultures without activation of telomerase. Here we show that the presence of continuous TTAGGG repeats at telomeres and rigorous control of replicative aging by telomere shortening appear to be conserved among anthropoid primates but is less effective in prosimian lemurs. PMID- 11777340 TI - Fibroblast contractile force is independent of the stiffness which resists the contraction. AB - Using a device named the cell force monitor, the contractile force developed by fibroblasts has been studied by measuring the macroscopic contraction of porous collagen-glycosaminoglycan (GAG) matrices over the first 24 h following cell attachment. In this paper, the effect of a variation in the stiffness that resists matrix contraction by cells on the contractile force generated by the cells was determined. Data from these experiments revealed that the contractile force generated by the fibroblasts was independent of the stiffness of the resistance within the range tested (0.7-10.7 N/m). These results suggest that during the time when fibroblasts are attaching to and spreading on collagen-GAG matrices the contractile forces they generate are force limited, not displacement limited. Therefore, the cytoskeletal mechanism of force generation, corresponding with cell elongation, is capable of increasing the displacement of adhesion sites in order to develop the same level of force. Although a detailed understanding of how the passive mechanical signals provided by substrate materials affect cell processes is still unavailable, in vitro modeling of cell-mediated contraction continues to provide useful information. PMID- 11777341 TI - Subchromosomal positioning of the epidermal differentiation complex (EDC) in keratinocyte and lymphoblast interphase nuclei. AB - The epidermal differentiation complex (EDC) at 1q21 is host to many structurally and functionally related genes coding for proteins involved in the differentiation process of keratinocytes. The grouping together of these genes which share spatial and temporal expression and interrelated functions is a remarkable genomic feature which has led to suggestions that the region may have a coordinated transcription control mechanism. With the growing awareness that the organization of the genome within the interphase nucleus is relevant to transcriptional activity, we have investigated the spatial organization of the EDC in the nuclei of keratinocytes, where the EDC genes are highly expressed, and lymphoblasts, where they are silent. Using 2D and 3D FISH we find that in keratinocyte nuclei the EDC is frequently positioned external to the chromosome 1 territory compared to lymphoblasts where the EDC more often adopts a peripheral or internal location. It has been previously shown that the MHC region can extend from the chromosome 6 territory in relation to transcriptional activity. This study of the EDC thus provides a further example of a gene-dense complex capable of assuming extraterritorial positioning in relation to cell type/transcription status. PMID- 11777342 TI - 1alpha,25-dihydroxyvitamin D3 stimulates phosphorylation of IkappaBalpha and synergizes with TPA to induce nuclear translocation of NFkappaB during monocytic differentiation of NB4 leukemia cells. AB - Treatment of NB4 acute promyelocytic leukemia cells with 1,25-dihydroxyvitamin D3 (1,25D3) or analogs 20-epi-22-oxa-24a,26a,27a-trihomo-1alpha,25-dihydroxyvitamin D3, 1,24-dihydroxy-22-ene-24-cyclopropylvitamin D3, 1alpha,25 dihydroxylumisterol3, or 1alpha,25(OH)2-d5-previtamin D3 in combination with TPA induces monocytic differentiation. The role of 1,25D3 in the induction of maturation has been shown to be a priming effect. Differentiation in response to these agents requires VDR-independent signaling of 1,25D3, PKC signaling, intracellular calcium, and calpain activity. In this study we identify the NFkappaB/IkappaB signaling pathway as a target of 1,25D3 and TPA action. One of the priming effects of 1,25D3 appears to be the rapid phosphorylation of serine residues on IkappaBalpha. On their own, 1,25D3, its analogs, and TPA do not alter IkappaBalpha expression; however, combinations of analogs with TPA result in a synergistic decrease in IkappaBalpha expression. Decreased expression of IkappaBalpha likely results from enhanced degradation, which allows the observed subsequent nuclear translocation of NFkappaB subunit p65. Since nuclear-localized NFkappaB was observed only in combination-treated cells, it is proposed that nuclear targets of NFkappaB are required for monocytic differentiation. Intracellular calcium and proteolytic activity are both necessary for the induction of IkappaB regulation and translocation of NFkappaB and are critical components of the nongenomic signaling cascades of the 1,25D3-induced differentiation pathway. PMID- 11777343 TI - Retinoic acid inhibits telomerase activity and downregulates expression but does not affect splicing of hTERT: correlation with cell growth rate inhibition in an in vitro cervical carcinogenesis/multidrug-resistance model. AB - Telomerase, a ribonucleoprotein complex of hTERT, hTR, and TP1, has been reported to be associated with carcinogenesis and multidrug resistance (MDR). This study used our in vitro human cervical multistep carcinogenesis/MDR model system in which normal human ectocervical and endocervical (HEN) cells were immortalized by HPV18 or 16, respectively, and subsequently transformed. The first evidence was found that immortalization and telomerase activation were correlated with increased expression specifically of two of the hTERT alternatively spliced mRNAs, one encoding wild-type protein containing the full-length functional reverse transcriptase (RT) region and one encoding a defective RT protein. Expression of neither hTERT mRNA containing full-length functional or defective RT motif was affected by transformation/MDR. All-trans-retinoic acid (ATRA) treatment of HPV-immortalized HEN-16-2 cells and transformed/MDR HEN-16-2/CDDP cells inhibited telomerase activity and downregulated expression of hTERT mRNAs containing full-length functional and a defective RT motif, but there were no changes in hTR and TP1 expression. Moreover, ATRA inhibited cell growth rate of HEN-16-2 and HEN-16-2/CDDP cells equally. These results provided the first evidence that ATRA equally in both immortalized and transformed/MDR cell lines inhibits telomerase activity and downregulates expression, but not splicing, of hTERT, and this is correlated with cell growth rate inhibition; the potential is implicated for applying ATRA to hTERT-targeted treatment of cervical cell carcinogenesis/MDR. PMID- 11777344 TI - Activation of the MEK/MAPK pathway is involved in bryostatin1-induced monocytic differenciation and up-regulation of X-linked inhibitor of apoptosis protein. AB - Induction of monocytic differentiation by bryostatin1 (bryo1) conferred on THP-1 leukemia cells the ability to resist Z-LLL-CHO-induced apoptosis. The mechanism of resistance developed during this process was investigated. Apoptosis resistance was associated with an enhanced expression of X-linked inhibitor of apoptosis protein (XIAP), an endogenous caspase inhibitor, in differentiated THP 1 cells. Bryo1 also increased the level of c-IAP-1, yet decreased the level of c IAP-2 in THP-1 cells, indicating that distinct regulatory mechanisms are operative. In addition, treatment of THP-1 cells with bryo1 induced a rapid and sustained activation of MEK, prior to the upregulation of XIAP and monocytic differentiation. Pretreatment of THP-1 cells with MEK inhibitors (U0126 and PD98059) prior to bryo1 induction blocked the expression of both XIAP and the c fms product (M-CSF receptor), a hallmark of monocytic differentiation, but not Bcl-2. In addition, the expression of XIAP in bryo1-treated cells was inhibited by CAPE, a NF-kappaB-specific inhibitor, indicating that its expression is under the transcriptional regulation of NF-kappaB downstream of the MEK/MAPK pathway. The importance of XIAP in mediating apoptosis resistance was illustrated in cells transiently transfected with XIAP, which conferred on THP-1 cells the ability to resist Z-LLL-CHO-induced apoptosis. These findings suggest that the expression of XIAP is linked to monocytic differentiation in bryo1-treated THP-1 cells and represents one of the potential antiapoptotic mechanisms acquired during this process. PMID- 11777345 TI - Expression profiles of p53-, p16(INK4a)-, and telomere-regulating genes in replicative senescent primary human, mouse, and chicken fibroblast cells. AB - Replicative senescence is known to be an intrinsic mechanism in determining the finite life span of in vitro cultured cells. Since this process is recognized as an evolutionarily conserved mechanism from yeast to mammalian cells, we compared the senescence-associated genetic alterations in the p53, p16(INK4a), and telomere regulatory pathways using replicative senescent human, mouse, and chicken fibroblast cells. Normal human diploid fibroblast (HDF; WI38) and chicken embryonic fibroblast (CEF) cells were shown to have a more extended in vitro proliferative potential than their mouse embryonic fibroblast (MEF) counterpart. In contrast to the HDF and CEF cells, MEF cells were shown to express telomerase mRNA and maintain telomerase activity throughout their in vitro life span. Functional p53 activity was shown to increase in the replicative senescent HDF and CEF cells, but not in replicative senescent MEF cells. On the other hand, there was a gradual elevation of p16(INK4a) expression with increased cell passages which reached a maximum in replicative senescent MEF cells. Taken together, the present study demonstrates that the p53, p16(INK4a), and telomere regulatory functions may be differentially regulated during replicative senescence in human, mouse, and chicken fibroblast cells. PMID- 11777347 TI - Re: false cell lines. PMID- 11777346 TI - A cell regulatory agent, CeReS-18, inhibits mouse 3T6 cell proliferation but not polyomavirus replication. AB - We have purified a cell regulatory sialoglycopeptide, CeReS-18, from intact bovine cerebral cortex cells. This is an 18-kDa molecule that reversibly inhibits cellular DNA synthesis and the proliferation of a wide array of target cells. In the present study, the effect of CeReS-18 on mouse 3T6 host cell proliferation and polyomavirus replication was investigated. The results showed that CeReS-18 was able to inhibit 3T6 cell cycling in a concentration-dependent, calcium sensitive, and reversible manner. Despite the inhibition of cell proliferation, CeReS-18 did not influence polyomavirus infection of 3T6 cells. Indirect immunofluorescent assays revealed that CeReS-18-treated, and cell cycle-arrested, 3T6 cells remained permissive to polyomavirus replication. Electron microscopy and immunogold labeling showed that new viral particles were assembled inside the nuclei of infected cells in the presence of CeReS-18 and during cell cycle arrest. The cellular requirements for the replication of polyomavirus DNA and the synthesis of viral proteins, as well as for the assembly of viral particles, therefore, remained available in CeReS-18-inhibited 3T6 cells. In addition, although polyomavirus infection can be mitogenic, infection of CeReS-18-treated 3T6 cells did not reverse the cell cycle arrest mediated by this cell cycle inhibitor. PMID- 11777348 TI - Image guided surgical navigation for removal of foreign bodies in the head and neck. AB - INTRODUCTION: The removal of foreign bodies in the head and neck area is often a surgical challenge due to a combination of difficult access and a close anatomical relationship of the foreign body to vital structures. Recent developments in computer-assisted surgery (CAS) have brought major improvements to the operating rooms for maxillofacial surgeons. The purpose of this paper is to report our experience in computer assisted removal of foreign bodies from the head and neck area, based on various clinical cases. PATIENTS: Computer assisted removal of foreign bodies from the head and neck area was performed in 11 patients. Three patients sustained gun shot wounds with remaining projectiles or fragments in the soft tissue. In six cases, objects related to a preceding surgical intervention were removed. Two patients presented with dislocated teeth in the facial or cervical soft tissues after 3rd molar surgery. METHOD: For surgical planning and intra-operative navigation, a computer based image guided surgery system (VectorVision(2), BrainLab) was used. RESULTS: In 10 of 11 cases the foreign bodies could be removed without major complications by a minimal invasive manner. More than 40 % of surgery time could be saved compared to similar interventions operated upon using conventional methods. CONCLUSION: In our opinion, the use of a computer based image guided surgical system is of great benefit when removing foreign bodies from the head and neck area. The minimally invasive access helps to prevent major complications such as injury to vital structures and allows a quicker operation. PMID- 11777349 TI - Computer assisted tumour resection of the skull base: case report. AB - This case report demonstrates computer assisted resection of a skull base tumour after combined chemotherapy and irradiation, in a 40-year-old man with a squamous cell carcinoma of maxilla, zygoma, orbit and skull base. The resection of the skull base was performed with computer assistance after conventional resection of the maxilla, midface, exenteration of the orbit and lymph node dissection. Following combined chemotherapy and irradiation, the original, pretherapeutic tumour extent was marked on the new, presurgical CT scan enabling resection of the skull base with the use of a navigation microscope. Thus planned resection from the presurgical CT could be transposed intraoperatively using the navigation system, and the skull base could be resected with precision. PMID- 11777350 TI - The role of angiography in the lower extremity using free vascularized fibular transplants for mandibular reconstruction. AB - BACKGROUND: Fibular osteocutaneous free tissue transfer represents the work horse procedure in the reconstruction of large oromandibular defects. Before the fibula is harvested the blood supply of the lower leg and foot should be examined, as the perfusion may be based predominantly on the peroneal artery and venae comitantes. To avoid postoperative ischaemia of the lower leg, adequate perfusion must be guaranteed before sacrificing the peroneal vessels. Anatomical variations and peripheral arterial occlusive disease add to the risk of ischaemia. Various methods of evaluating the blood supply have been described. MATERIAL AND METHODS: Fifty-two consecutive cases of fibular flaps were evaluated to study the arterial blood supply of the lower extremity. For angiography, the right femoral artery was punctured using the Seldinger technique and a total of 20-25 ml contrast medium (Imeron 300) was infused and images required at a rate of 0.5/sec. RESULTS: A patent three-vessel supply to both feet could only be detected in 21 patients. Thirty-one angiograms revealed anatomic and/or arteriosclerotic alterations. Angiography provided accurate information in all patients and allowed successful fibular transfer in those patients who were found preoperatively to have regular conditions. CONCLUSION: Preoperative assessment of the blood supply of the lower extremity is important before fibular osteocutaneous free tissue transfer. We advocate angiography as interpretation is not examiner dependent. PMID- 11777351 TI - Repair of composite zygomatico-maxillary defects with free bone grafts and free vascularized tissue transfer. AB - INTRODUCTION: Three-dimensional repair of the zygomatico-maxillary defect calls for an elaborate technique to achieve facial symmetry and correct globe position. We present a technique, which combines the use of a free vascularized soft tissue flap and free bone grafts for repair of composite zygomatico-maxillary defects. PATIENTS: Three patients that underwent radical resection of the maxilla and the zygoma have undergone facial reconstruction using this technique. The mean follow up was 9 months. METHODS: The key points of this technique are: (1) precise reconstruction of the zygomatico-maxillary complex including the orbit; (2) creation of a skeletal framework for canthopexy and suspension of the free flap; (3) repair of through-and-through soft tissue defects with a folded musculocutaneous free flap; and (4) simultaneous harvesting and reconstruction using two surgical teams to reduce the duration of surgery. RESULTS: Reconstruction of the zygomatico-maxillary complex could be successfully accomplished in a single surgical procedure. CONCLUSION: This paper presents a method of repairing zygomatico-maxillary defects with free bone grafts and vascularized soft tissue. However, this concept has yet to be reviewed in the long term. PMID- 11777352 TI - Functional and aesthetic reconstruction of full-thickness cheek, oral commissure and vermilion. AB - PURPOSE: This paper presents surgical techniques for reconstruction of the cheek, oral commissure and vermillion in the repair of full-thickness cheek defects after resection of buccal-mucosal squamous cell carcinoma. PATIENTS AND METHODS: Four reconstructions in one-stage surgery with either a free radial forearm flap or a rectus abdominis musculocutaneous flap for cheek and oral commissure were carried out. There were combined with a new approach for vermillion advancement flaps. Most challenging was the need not only for morphological reconstruction of the orifice, but also for physiological reestablishment of sphincteric and sensory functions in the vermillion. RESULTS: Morphological and physiological reconstruction of the lip with sphincteric and sensory functions was attained. CONCLUSION: This valuable reconstruction technique was demonstrated in large, full thickness defects involving the cheek, oral commissure and vermilion. PMID- 11777353 TI - Oral commissure reconstruction with split masseter muscle transposition and cheek skin flap. AB - Satisfactory reconstruction of the cheek involving the oral commissure is always challenging. A 64-year-old male patient underwent full-thickness repair of a cheek defect involving the oral commissure following excision of squamous cell carcinoma. Reconstruction was performed with a cheek skin flap combined with split masseter muscle transposition. This method was found to be useful for reconstructing the oral commissure with good functional and aesthetic results. PMID- 11777354 TI - Temporal galeal fascia cover of custom-made gold lid weights for correction of paralytic lagophthalmos: long-term evaluation of an improved technique. AB - BACKGROUND: Chronic paralytic lagophthalmos is a condition that is often conservatively treated with ophthalmic ointments and eye drops, but usually requires definitive surgical correction. PURPOSE: An effective modification of the gold lid loading technique is described, which we have found to be the simplest and most reliable method for lid reanimation. MATERIAL: After empiric evaluations with lead fisherman's weights 'glued' to the eyelid, a custom-made gold lid weight is made by a jeweller on the basis of the tarsal dimensions of the individual patient, and then sutured to the tarsus under local anaesthesia and covered with a fine sheet of temporal galea. Other ancillary procedures (lower lid suspension, lateral tarsal strip, lateral tarsoplasty) are added as required. METHODS: Between 1990 and 1996, 27 patients underwent this type of surgery, of whom 24 were re-evaluated after a mean follow-up period of 73.2 months (range 36-96 months), 14 of these for a minimum of 5 years. RESULTS: None of the gold weights was extruded, all 24 patients experienced marked improvement of their dry-eye symptoms and expressed a high degree of satisfaction. Six patients underwent further minor surgery (lateral McLaughlin tarsorrhaphy) in order to improve relative underaction. Two patients had ptosis (less than 2 mm of asymmetry) of the affected side but refused further correction. CONCLUSION: The use of custom-made gold lid weights and a protective galeal layer is a simple, reliable and successful means for permanently rehabilitating paralysed eyelids. PMID- 11777355 TI - Endoscopically assisted Le Fort I osteotomy. AB - OBJECTIVES: A new technique of the Le Fort I osteotomy using endoscopic techniques through limited approaches has been evaluated. PATIENTS: This technique was first carried out successfully in a study on six cadavers. Thereafter we performed endoscopically assisted Le Fort l osteotomy in two patients. METHODS: Four vertical incisions were used in the vestibule (paranasally and posteriorly) as approaches. The endoscope allowed direct visualization of the osteotomy of the maxilla including the pterygomaxillary junction. The osteotomies could be accomplished with a straight 4 mm osteotome for medial and lateral antral walls and nasal septum and a curved osteotome for the pterygomaxillary junction. RESULTS: The procedures were successful. The descending palatal arteries could be preserved in all cases as a result of endoscopic control. Rigid fixation of the downfractured maxillae was carried out using self-drilling titanium screws and plates. CONCLUSION: Endoscopic visualization allowed safe osteotomy of the medial antral wall preserving the descending palatal artery in all cases and hence less bleeding. Postoperative oedema and swelling in the two clinical cases was definitely reduced when compared with the conventional technique. The time needed for these first two clinical cases was approximately 1 h 30 min, i.e., about 30 min more than with the open technique. Further experience and experimental work, and refinements in technique will help to improve this procedure in its clinical application. PMID- 11777356 TI - High-resolution ultrasonography of the TMJ: helpful diagnostic approach for patients with TMJ disorders ? AB - PURPOSE: The purpose of this study was to investigate patients with a clinical diagnosis of internal derangement to determine the diagnostic value of static high resolution ultrasonography (HR-US) when compared with magnetic resonance imaging (MRI). PATIENTS: Sixty-six patients (132 temporomandibular joints [TMJs]) with a clinical diagnosis of internal derangement were investigated by HR-US and MRI. METHODS: MRI and HR-US investigations were performed by experienced radiologists. The sonograms were done with a real-time 12-Mhz linear-array scanner. The HR-US interpretation errors were re-evaluated retrospectively by the same radiologist knowing the MRI results by comparing these with the 'prospective' and 'retrospective' diagnoses. The prospective and retrospective diagnoses were also compared with each other. RESULTS: Eighty-seven of the 132 TMJs had a disc displacement proved by MRI in the closed-mouth position. At maximum mouth opening, 54 TMJs had a disc displacement. The prospective interpretations showed a sensitivity and specificity of 78% each, accounting for an accuracy of 78%. At maximum mouth opening, HR-US resulted in a sensitivity of 61%, a specificity of 88% and an accuracy of 77%. The retrospective interpretations yielded a sensitivity of 90%, a specificity of 84% and an accuracy of 88% in the closed-mouth position. At maximum mouth opening, HR-US showed a sensitivity of 73%, a specificity of 95% and an accuracy of 86%. CONCLUSION: HR-US is suitable for the detection of disc displacements in the TMJ. However, further studies may be warranted to reduce the proportion of false positive interpretations, thereby avoiding the application of unnecessary treatment. PMID- 11777357 TI - Jacob's disease: report of two cases and review of the literature. AB - Jacob's disease is a rare condition consisting of new joint formation between the coronoid process of the mandible and the inner aspect of the zygomatic arch. Strictly speaking, it was first described by the French anatomist Oscar Jacob in 1899, although in 1853 von Langenbeck had described coronoid process hyperplasia. The pathogenesis of both conditions remains unknown. In this paper we present two new cases and a complete review of the literature on Jacob's disease, of which we have found only 12 cases. Due to the low prevalence of this condition, its diagnosis is not straight forward. PMID- 11777359 TI - Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. AB - BACKGROUND: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis. OBJECTIVE: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis. DESIGN: 2-year randomized, double-blind, placebo-controlled clinical trial. SETTING: 2 outpatient rheumatology clinics. PATIENTS: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs. INTERVENTION: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication. MEASUREMENTS: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months. RESULTS: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group. CONCLUSIONS: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. PMID- 11777361 TI - Recovery rate and prognosis in older persons who develop acute lung injury and the acute respiratory distress syndrome. AB - BACKGROUND: The incidence of acute respiratory failure requiring mechanical ventilation increases 10-fold from the ages of 55 to 85 years, yet the rate of recovery and outcomes in older persons who develop acute lung injury are poorly defined. OBJECTIVE: To examine age as an independent risk factor in recovery and intensive care unit discharge after acute lung injury. DESIGN: Prospective cohort study. SETTING: 10 U.S. university-based medical centers. PATIENTS: 902 mechanically ventilated patients enrolled in randomized, controlled trials for the treatment of acute lung injury. All patients were managed according to a standardized protocol for ventilator management and weaning. MEASUREMENTS: Frequency and time to achieve well-defined recovery landmarks, duration of ventilation and intensive care unit stay, and survival. RESULTS: Median duration of mechanical ventilation was 19 days (interquartile range, 7 to >28 days) for patients 70 years of age or older (n = 173) compared with 10 days (interquartile range, 5 to 26 days) for patients younger than 70 years of age (n = 729) (P < 0.001). The duration of intensive care unit stay was 21 days for the older group (interquartile range, 11 to >28 days) and 16 days for the younger group (8 to >28 days) (P = 0.004). Survival rates decreased across increasing decades of age (P < 0.001): Patients younger than 70 years of age had a greater 28-day survival rate than patients 70 years of age or older (74.6% vs. 50.3%; P < 0.001). The proportion of survivors achieving physiologic recovery landmarks did not differ between the older and younger age groups, and the median time to pass a 2-hour spontaneous breathing trial was similar between both the older and younger patients (4 days vs. 5 days; P > 0.2). After passing a spontaneous breathing trial, however, older patients required 1 more day than younger patients to achieve unassisted breathing (P = 0.002) and 3 more days to leave the intensive care unit (P = 0.005). In a multivariable Cox proportional hazards analysis, age of 70 years or older was a strong predictor of in-hospital death (hazard ratio, 2.5 [95% CI, 2.0 to 3.2]; P < 0.001). CONCLUSIONS: Although the survival rate among patients 70 years of age or older was high, these patients were twice as likely to die of acute lung injury compared with their younger counterparts, even after adjustment for covariates. Older survivors recovered from respiratory failure and achieved spontaneous breathing at the same rate as younger patients but had greater difficulty achieving liberation from the ventilator and being discharged from the intensive care unit. PMID- 11777360 TI - Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993-1999. AB - BACKGROUND: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens. OBJECTIVE: To estimate the prevalence of H. pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H. pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time. DESIGN: Meta-analysis using patient-level data. SETTING: 20 nationwide trials of H. pylori eradication. PATIENTS: 3624 men and women, each of whom contributed one isolate. MEASUREMENTS: Rates of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study. RESULTS: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% [360 of 3571 patients]), 36.9% (CI, 35.1% to 38.7% [1063 of 2883 patients]), and 1.4% (CI, 1.0% to 1.8% [48 of 3486 patients]), respectively. In multivariable analyses, multiple risk factors were associated with resistance to individual agents. Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010). Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001). Amoxicillin resistance was low and was not significantly associated with any risk factor. In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied. CONCLUSIONS: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H. pylori treatments in the empirical setting. PMID- 11777362 TI - Anomalies of the inferior vena cava in patients with iliac venous thrombosis. AB - BACKGROUND: Cases of deep venous thrombosis in the lower extremities triggered by abnormalities of the vena cava have been reported. OBJECTIVE: To describe anomalies of the inferior vena cava in patients with deep venous thrombosis. DESIGN: Prospective, consecutive case series. SETTING: University Hospital, Graz, Austria. PATIENTS: 97 patients with deep venous thrombosis. INTERVENTION: Sonography, venography, or both to diagnose deep venous thrombosis; magnetic resonance angiography to image the inferior vena cava. MEASUREMENTS: Anomalies of the inferior vena cava imaged by magnetic resonance angiography. RESULTS: 31 of 97 patients showed thrombotic occlusion of iliac veins (common and external iliac vein [ n = 29] or external iliac vein [ n = 2]). Five of 31 patients (3 men, 2 women) had an anomaly of the inferior vena cava. Anomalies were missing inferior vena cava, hypoplastic hepatic segment, and missing renal or postrenal segments. Patients with anomalies were significantly younger than the 92 patients without (mean age+/-SD, 25+/-6 years vs. 53+/-19 years; P = 0.002). In 2 patients with anomalies, the thrombotic occlusion was recurrent. CONCLUSIONS: An anomaly of the inferior vena cava should be suspected if thrombosis involving the iliac veins is seen in patients 30 years of age or younger. Patients with both an anomaly and thrombosis may be at higher risk for thrombotic recurrence. PMID- 11777363 TI - The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. AB - Because use of herbal remedies is increasing, a risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk-benefit assessments are not completely reliable, and much knowledge is still lacking. PMID- 11777364 TI - Therapeutic angiogenesis for coronary artery disease. AB - A large body of evidence in animal models of ischemia shows that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. Many cytokines have angiogenic activity; those that have been best studied in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger-scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein and have not yet shown significant improvement in exercise time or angina compared with placebo. Larger-scale placebo-controlled studies of gene transfer are in progress. Clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor-cell or stem-cell supplementation, to provide safe and effective therapeutic myocardial angiogenesis. Determination of which growth factors or cells are required to optimize therapeutic neovascularization in an individual patient should be a goal of future research. PMID- 11777365 TI - Caring for patients at the end of life: reflections after 12 years of practice. AB - Physicians have the privilege and authority to assist patients and their families at the end of life. Regardless of diagnosis, commonalities occur in the dying process, and palliative care benefits patients and families. This perspective chronicles my experience over 12 years caring for 95 patients at the end of life, illustrated in part with six vignettes. I describe interactions with families, discuss logistic issues around dying, examine the do-not-resuscitate issue, and highlight experiences with home visits. I also touch on how I communicate with the family after a death. I hope to express the significance of what I have learned while assisting patients and families at this critical juncture. PMID- 11777366 TI - Are long-term very low doses of prednisone for patients with rheumatoid arthritis as helpful as high doses are harmful?. PMID- 11777367 TI - Pharmacist scope of practice. AB - This paper explores the increased scope of practice of U.S. pharmacists. It presents background information on the pharmacy profession and outlines how the medical profession can work with pharmacists to enhance patient safety and quality of care. The paper calls for further research on the effects of pharmacy automation and the move to the Doctor of Pharmacy degree on pharmacy practice. Other positions include support for patient education and hospital rounds, opposition to independent pharmacist prescriptive privileges and initiation of drug therapy, increased use of the pharmacist as immunizer (as allowed by state law), and continued support for the American College of Physicians-American Society of Internal Medicine 1990 therapeutic substitution position. PMID- 11777368 TI - Osteoarthritis: new insights. PMID- 11777369 TI - Osteoarthritis: new insights. PMID- 11777370 TI - Osteoarthritis: new insights. PMID- 11777371 TI - Osteoarthritis: new insights. PMID- 11777373 TI - Formation and Structure of Artificial Cellulose Spherulites via Enzymatic Polymerization. PMID- 11777372 TI - Summaries for patients. Prednisone for rheumatoid arthritis. PMID- 11777374 TI - Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules. AB - Several types of sugar-installed poly(ethylene glycol)/poly(DL-lactide) (sugar PEG/PLA) block copolymers were synthesized. The synthesized block copolymer forms a core-shell type polymeric micelle in aqueous media possessing sugar molecules on its surface. Specific recognition of lectin proteins with the sugar molecules on the micelle surface was observed. Both the galactose- and lactose-installed micelles specifically interacted with RCA-1; on the other hand the mannose installed micelle interacted specifically with Con A. With a lectin-immobilized affinity column, the cluster effect of the sugar molecule on the micelle surface was clearly observed. PMID- 11777375 TI - Effect of salt and heating on a mesoscopic structure composed of ovalbumin globules in aqueous solution. AB - Mesoscopic structural changes of an ovalbumin solution by heating and adding NaCl have been investigated with a small-angle neutron scattering method. In the natural solution, a broad peak at q = 0.057 A(-1), which disappeared by adding NaCl, indicates the existence of an electrostatic long-range interaction between the ovalbumin globules. Along with the broad peak, a prominent intensity increase in a very small q region was observed on heating except for the initial and final stages, indicating the coexistence of a disordered structure of the denatured ovalbumin and a regular-interspacing structure of the natural ovalbumin globules. Though the macroscopic feature in the final stage, whether the solution forms a gel (10 wt %) or not (5 wt %), strongly depended on the concentration of the ovalbumin, the scattering profiles showed a common characteristic feature: the appearance of a new peak around q = 0.023 A(-1), which indicates the emergence of another regular structure. PMID- 11777376 TI - Characterization of polyanionic collagen prepared by selective hydrolysis of asparagine and glutamine carboxyamide side chains. AB - Acellular polyanionic collagen materials intended for biomaterial and tissue engineering uses were prepared by the selective and controlled hydrolysis of carboxyamides from asparagine and glutamine residues of type I collagen present in pericardium, tendon, and intestinal submucosa, all from bovine origin. The increase in carboxyl groups was from 26 +/- 14 (12 h of hydrolysis) to 134 +/- 12 (144 h of hydrolysis). Although collagen triple helix structure of polyanionic materials was preserved in all cases, a decrease in thermal stability and a gradual loss in the ability of collagen molecules to form fibrils were detected with increasing carboxyl content, probably as a result of changes in the pattern of electrostatic interaction. The resulting materials were basically acellular polyanionic collagen matrixes associated with an elastin content dependent on the time of hydrolysis. The results showed that the procedure described in this work may be a useful process for preparation of collagen biomaterials with variable physicochemical properties and macromolecular arrangement with respect to fibril formation and with potential use in tissue engineering. PMID- 11777377 TI - Depletion-induced demixing in aqueous protein-polysaccharide solutions. AB - We explore the separation of aqueous protein-polysaccharide solutions into two liquid phases. In particular, we have studied the combinations beta lactoglobulin/pullulan, alpha-lactalbumin/pullulan, and other examples from the literature under a variety of conditions such as varying salt content, pH (in most cases at the isoelectric point), and protein radius. We restrict ourselves to relatively small proteins (globular) and long polysaccharide chains. The mechanism behind the phase separation is explained in terms of the depletion interaction (i.e., the cross-interaction) in a suspension of small spheres (proteins) immersed in a semidilute solution of coils (polysaccharide) forming an entangled network. Weak attractions between the spheres have been taken into account by assuming the formation of small clusters. As a general rule, we find that the depletion free energy per protein particle governing the protein partitioning in the phase equilibrium is linear in the polysaccharide concentration over the whole range of experimentally accessible coexistence curves. Furthermore, the proportionality constant is shown to be a very useful quantity to understand the characteristics of the coexistence curves. The linearity thus found is supported by theoretical arguments developed by de Gennes and Odijk. PMID- 11777378 TI - Molecular basis of C(2+)-induced gelation in alginates and pectins: the egg-box model revisited. AB - For many ionic polysaccharides, the ability to form gels in the presence of divalent cations such as calcium is the key to biological functions and technological applications. This is particularly true for alginates and pectins, where the regular occurrence of respectively alpha-L-(1-4)-guluronate residues and alpha-D-galacturonate residues generates ordered templates for polymer chain associations that are involved in physical gels. The molecular basis responsible for the strength and the stereospecificity of calcium interactions for the two polysaccharides were investigated in a previous paper (Braccini; et al. Carbohydr. Res. 1999, 119). In the present work, a novel molecular modeling procedure has been developed; it involves a pairing procedure that evaluates all the possible associations of the ordered polyuronate chains with calcium ions to form dimers. Starting from the stable ordered forms of polygalacturonate and polyguluronate, all possible ways to form Ca(2+)-bridged dimers were computed; the parallel and antiparallel relative arrangements of the chains were also considered. Despite the structural analogy between polyguluronate and polygalacturonate chains, significant differences at the level of chain-chain associations are found. The popular "egg box model" can still be referred to in the case of polyguluronate. However, it cannot be used to describe a pectate junction zone as the unique feature of two consecutive chelation site per repeat, that provides a favorable entropic contribution to the interchain association is not reproduced by this pioneering model. The body of these results corroborates the two-stage process in the mechanism of calcium gelation, where the formation of strongly linked dimer associations is followed by the formation of weak inter dimer associations mainly governed by electrostatic interactions. PMID- 11777379 TI - Hindered diffusion in polymer-tethered membranes: a monolayer study at the air water interface. AB - Polymer-tethered phospholipid bilayers, which are based on a phospholipid lipopolymer mixture, represent a very promising approach to stabilize complex biomimicking composite membranes. Furthermore, they are interesting model systems to study problems of hindered diffusion in two-dimensional liquids. Here, we present fluorescence recovery after photobleaching experiments (FRAP) on mixed phospholipid-lipopolymer monolayers of DMPC and DSPE-EO(45) at the air-water interface. In contrast to recent polymer-tethered bilayer experiments where the hydrophobic lipopolymer anchors behaved as immobile obstacles within the fluid phospholipid matrix,(1) this paper investigates the influence of mobile lipopolymer obstacles on the lateral diffusion of phospholipids. We found that the lateral diffusion of phospholipids with D = 7.1 +/- 0.5 microm(2)/s is independent of the lipopolymer obstacle concentration if adjacent polymer chains do not interact with each other. However, the diffusion coefficient of nontethered phospholipids gradually decreases from D = 7.1 +/- 0.5 microm(2)/s to D = 3.4 +/- 0.1 microm(2)/s in the case of increasing polymer-polymer interactions based on frictional coupling. This can be understood by a slowing down of the obstacle mobility. While phospholipids still show a significant lateral diffusion as long as the polymer moieties interact with each other only via frictional coupling, they become rather immobile (D = 0.9 +/- 0.1 microm(2)/s) if lipopolymers form a two-dimensional physical network. PMID- 11777380 TI - Processability of cottonseed proteins into biodegradable materials. AB - The manufacture of biodegradable materials from agricultural sources is a real challenge, because of environmental concerns and the need to make full use of resources. Cottonseed is an important protein source that could be used in nonfood applications, as a substitute for synthetic polymers. For the first time, the viscoelastic behavior of cottonseed protein isolate (CPI), plasticized with glycerol, was characterized in order to determine the temperature range within which cottonseed protein-based materials can be formed by extrusion or thermomolding. Research involved three main techniques: dynamic mechanical analysis to study the alpha protein relaxation associated with glass transition, as a function of plasticization by glycerol; DSC analysis to determine the effect of glycerol content on the protein denaturation and degradation temperatures; and ATG-TG/FTIR to characterize the protein degradation. The results indicated that cottonseed proteins are thermoplastics with a T(g) ranging from 80 to 200 degrees C when the glycerol content varies from 0% to 40% (w/w, dry basis). The proteins' thermal denaturation temperature increased from 141 (without glycerol) to 195 degrees C in the presence of 40% (w/w) glycerol. Protein degradation occurred at 230 degrees C irrespective of glycerol content, with the release of a variety of compounds. Glycerol acts as a plasticizer and thermal stabilizer of the proteins and increases the range of temperatures (80-175 degrees C) at which the material can be processed. PMID- 11777381 TI - Polylactones. 55. A-B-A triblock copolymers of various polypeptides. Syntheses involving 4-aminobenzoyl-terminated poly(epsilon-caprolactone) as B block. AB - A telechelic poly(epsilon-caprolactone) having a degree of polymerization (DP) around 25 and two 4-aminobenzoyl chain ends was used as a macroinitiator for the ring-opening polymerization of various alpha-amino acid N-carboxyanhydrides (NCAs). Glycine-NCA, L-alanine-NCA, L-phenylalanine-NCA, and gamma-benzyl-L glutamate-NCA served as monomers and the NCA/macroinitiator ratio was varied between 20:1, 40:1, and 100:1. In the case of L-Phe-NCA, a ratio of 200:1 was also used. It was demonstrated by means of model studies, that the NCAs may react almost quantitatively with the 4-aminobenzoyl end groups despite their relatively low nucleophilicity. The isolated triblock copolymers were characterized by viscosity measurements and by (1)H NMR spectroscopy with regard to their composition (which in most cases paralleled the feed ratios). However, in the case of gamma-Bzl-Glu-NCA mixtures of di- and triblock copolymer were obtained. The secondary structures of the solid copolymers were examined by IR spectroscopy and (13)C NMR CP/MAS spectroscopy. It was found that the alpha-helix/beta-sheet ratio of the poly(L-Ala) and poly(L-Phe) blocks increases with their average length, according to the NCA/macroinitiator ratio. PMID- 11777382 TI - Macroporous copolymer matrix: 1. Effectiveness of different diisocyanate spacer arms to bind cyclodextrins. AB - Cross-linked macroporous beaded polymer matrices, with pendant hydroxyl groups, were synthesized by the copolymerization of 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate using suspension polymerization methodology. Novel affinity chromatography matrices were synthesized using various diisocyanates as bifunctional reagents to couple the macroporous polymeric supports, of controlled particle size distribution, with alpha and beta-cyclodextrins. The optimal conditions to couple the hydroxyl groups of cyclodextrin (ligand) and the polymeric supports through urethane linkages were established iteratively using various diisocyanates. Efficacy of ligand binding on the matrix and nonspecific interactions of the synthesized affinity matrices were evaluated to establish the best support and spacer arm. 2,4-Tolylene diisocyanate was established as the best spacer arm on the basis of high ligand binding and low nonspecific interactions. The characteristics of the synthesized affinity matrices toward the adsorption of alpha and beta-cyclodextrin glycosyltransferase (CGTase) were investigated. The binding of beta-CGTase was the highest on affinity matrices with the polymeric methylene diisocyanate spacer. The optimal conditions to regenerate the matrices were also established. PMID- 11777383 TI - Exploitation of reactivity and selectivity in cellulose functionalization using unconventional media for the design of products showing new superstructures. AB - A variety of new cellulose solvents was investigated toward their potential as media for the functionalization of the polyglucane. Thus, mixtures of dimethyl sulfoxide (DMSO)/tetrabutylammonium fluoride trihydrate (TBAF), N methylmorpholine-N-oxide (NMMNO)/DMSO, melts of LiClO(4).3H(2)O, and aqueous solutions of Ni(tren)(OH)(2) [tren = tris(2-aminoethyl)amine] were applied as reaction media. In case of the new solvent, DMSO/TBAF its usefulness for derivatization reactions including the etherification with sodium monochloroacetate and the acylation with vinyl esters of carbonic acids was studied. The structural features of the products were analyzed by means of (1)H NMR spectroscopy (after depolymerization or peresterification), (13)C NMR spectroscopy, and HPLC after complete hydrolytic chain degradation. The results were compared with those obtained from derivatives prepared using the solvent N,N dimethylacetamide (DMAc)/LiCl and conventional, heterogeneous synthesis. It can be shown that in case of carboxymethylation reactions the reaction medium applied has a drastic influence both on the course of reaction and on the structural features of the products. A highly efficient tool was found to be atomic force microscopy (AFM), showing remarkable differences in the superstructures of the differentially synthesized derivatives. PMID- 11777384 TI - Biological activities of carbohydrate-branched chitosan derivatives. AB - Two types of biological activities of the carbohydrate-branched chitosan derivatives were investigated. One is the specific interaction with lectins and bacterium. The other is activation of canine polymorphonuclear leukocyte (PMN) cells. The specific bindings of the L-fucose-branched chitosan derivative with Ulex europaeus agglutinin I (UEA-I) and the N-acetyl-D-glucosamine-branched chitosan derivative with Concanavalin A (Con A) were confirmed by a surface plasmon resonance technique. The specific aggregation of the fluorescence-labeled L-fucose-branched chitosan derivative with Pseudomonas aeruginosa was observed by fluorescent microscopic observation. The aggregation would be attributed to the specific binding between the L-fucose-branched chitosan derivative and PA-II receptor on the cell surface of P. aeruginosa. The influence of the chitosan derivatives on the active oxygen species generation from canine PMN cells was also investigated by the luminol-aided chemiluminescence method. The chemiluminescence responses depended on the degree of substitution and water solubility of the chitosan derivatives. The water-insoluble chitosan derivatives would stimulate the PMN cells by a phagocytosis mechanism, and the water-soluble ones would sensitize the PMN cells by a priming mechanism. PMID- 11777385 TI - (13)C nuclear magnetic relaxation study of segmental dynamics of the heteropolysaccharide pullulan in dilute solutions. AB - (13)C spin-lattice relaxation times (T(1)) and nuclear Overhauser enhancements (NOE) were measured as a function of temperature and magnetic field strength for the heteropolysaccharide pullulan in two solvents, water and dimethyl sulfoxide. The relaxation data of the endocyclic ring carbons were successfully interpreted in terms of chain segmental motions by using the bimodal time-correlation function of Dejean de la Batie, Laupretre, and Monnerie. On the basis of the calculated correlation times for segmental motion, the flexibilities of the pullulan chain at a repeat-unit level have been studied and compared with the segmental mobility of the homopolysaccharides amylose and dextran in the same solvents. The internal rotation of the free hydroxymethyl groups about the exocyclic C-5 [bond] C-6 bonds superimposed on segmental motion has been described as a diffusion process of restricted amplitude. The rate and amplitude of the internal rotation of the free hydroxymethyl groups were not affected by the local geometry of the pullulan chain. PMID- 11777386 TI - Compatibility of gelatin and dextran in aqueous solution. AB - The temperature-composition phase diagrams of aqueous solutions of gelatin and dextran, which show liquid/liquid phase segregation, were explored at temperatures above the gelation temperature of gelatin. The compositions of the coexisting phases were found to show practically no dependence on temperature between 40 and 80 degrees C. Also, the total polymer concentration at which phase separation occurred was found to be nearly independent of temperature. These observations suggest an entropy-driven phase separation. An explanation in terms of depletion, reversible clustering, and subsequent transient network formation of gelatin at temperatures well above the temperature of gelation is suggested. Phase separation is found to be accompanied by strong fractionation of the molar mass distribution in the two phases. PMID- 11777387 TI - Purification and characterization of poly(aspartic acid) hydrolase from Sphingomonas sp. KT-1. AB - Poly(aspartic acid) (PAA) hydrolase was purified from Sphingomonas sp. KT-1 (JCM10459). The purified hydrolase degraded thermally synthesized PAA to oligomers. The molecular mass of PAA hydrolase was 30 kDa and the isoelectric point was 8.9. The optimum values of pH and temperature for PAA degradation were 10.0 and 40 degrees C, respectively. The investigation of the effect of inhibitors for the PAA-degrading activities has revealed that the PAA hydrolase is a serine-type hydrolase. The structural analysis of PAA-degraded products using (1)H and (13)C nuclear magnetic resonances has indicated that the purified enzyme hydrolyzes selectively the beta-amide linkage connecting with beta aspartic acid units in PAA. PMID- 11777388 TI - Interactions of phospholipid bilayer with chitosan: effect of molecular weight and pH. AB - Chitosan has demonstrated its potentials as a gene carrier and a membrane perturbant for subsequent drug delivery to cells. However, there is currently a lack of experimental correlation between the physiochemical properties of chitosan and the resulting degree of lipid bilayer destabilization. In this study, the effect of pH and chitosan molecular weight on the interaction between chitosan and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer was examined with cross-polarization microscopy, differential scanning calorimetry (DSC), and Fourier transform- (FT-) Raman spectroscopy. Cross-polarized images showed that the direct hydration of the DPPC/chitosan mixture led to the formation of larger DPPC multilamellar vesicles (MLV), and pure chitosan also induced fusions of individual MLV. Under the influence of chitosan, the calorimetric enthalpy of DPPC was reduced in a concentration-dependent manner, and a new phase appeared at 28 degrees C during sample cooling. Even the lowest chitosan mole fraction of 0.04% reduced the cooperative unit of the DPPC bilayer by more than 70%. In addition, the electrostatic effect between chitosan and DPPC tuned the degree of membrane bilayer perturbation. Reduction of pH increased the number of protonated amines on the chitosan backbone and caused further disruption on the membrane organization. Mixing DPPC with chitosan in an organic medium before hydration enhanced the hydrophobic interactions between the two molecules and greatly reduced the cooperative unit among individual lipids during the main phase transition. The increase of chitosan molecular weight also affected the cooperativity in the thermotropic transition of DPPC bilayer. FT-Raman spectroscopy provided additional evidence that chitosan directly perturbed the organizations of the hydrophobic inner core of the DPPC bilayer. PMID- 11777389 TI - Terminally alkylated heparin. 1. Antithrombogenic surface modifier. AB - Terminally alkylated heparin was prepared by reducing the terminal end of heparin and subsequent lactone formation, followed by ring-opening reaction with alkylamine. The alkyl groups used include butyl, octyl, lauryl, and stearyl. These alkylated heparins adsorbed on the poly(ethylene terephthalate) film from their respective aqueous solutions. The adsorptivity and its stability in buffer solution, complexation compatibility with antithrombin III (ATIII), were enhanced with larger alkyl-group-derivatized heparins. These were assessed using a confocal laser scanning microscope. The "heparin surfactant" developed here may be used for ensured short-term "system antithrombogenicity" of assembled extracorporeal circulatory devices or circuits. PMID- 11777390 TI - Terminally alkylated heparin. 2. Potent antiproliferative agent for vascular smooth muscle cells. AB - The antiproliferative activity of alkylated heparin, in which the terminal end of heparin is derivatized with an alkyl group (butyl, octyl, lauryl, stearyl), was examined using vascular smooth muscle cells. The proliferation of cells, which were growth-arrested prior to addition of heparin, was inhibited in proportion to both increase in the chain length of the alkyl group of alkylated heparin and alkylated heparin concentration in the serum-containing medium. The antiproliferative activity of stearyl group derivatized heparin was significantly stronger than that of nonmodified heparin. Little proliferation was observed at high dose (500 microg/mL). Confocal laser scanning microscopic observation indicated that alkylated heparin was accumulated on the cell membranes at an early incubation time, followed by homogeneous distribution of intracellular space. The therapeutic potential of alkylated heparin for preventing restenosis after balloon angioplasty is discussed. PMID- 11777391 TI - Single molecule study of xanthan conformation using atomic force microscopy. AB - Conformations of individual macromolecules of the biopolymer xanthan were investigated using atomic force microscopy (AFM). Xanthan from very dilute solutions (1 ppm) was allowed to adsorb onto freshly cleaved mica and examined using tapping mode AFM under ambient conditions. The secondary structure of xanthan was probed by heating the polymer and gradually cooling, which denatured and renatured the polymer. When salt was present, renatured xanthan formed a double helical structure, consistent with the structure of native xanthan. In pure water, renaturation was not complete as what appeared to be single helical structures were observed. The number-average contour length (L(n)) of the polymer in its single helical state was 1651 nm. In the double helical state, induced by the addition of salt, L(n) decreased to 450 nm (in 0.5 M KCl). The chains also became less rigid as salt was added. The persistence length decreased from 417 nm in pure water to approximately 150 nm in 0.1 or 0.5 M KCl. This indicated a trend toward more flexible molecules when salt was present. Calculations of end-to-end distances based on equilibrium and projected conformations confirmed that the xanthan chain conformation on the mica surface was at equilibrium and was therefore representative of the conformation of xanthan in solution. The single molecule AFM technique eliminates one common bias of solution techniques, which is the determination of an average signal between aggregates and dissolved molecules. It is thus a useful complement to solution-based methods for determining physical-chemical properties of biopolymers. PMID- 11777392 TI - Fibrinogen-conjugated albumin polymers and their interaction with platelets under flow conditions. AB - Albumin polymers, having an average diameter of 1020 +/- 250 nm, were prepared by the disulfide polymerization of recombinant human serum albumin (rHSA) by controlling of the pH and temperature. Fibrinogen could be conjugated on the surface of an albumin polymer using N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). Under flow conditions, the fibrinogen-conjugated albumin polymers (fibrinogen-albumin polymers) were irreversibly attached to the platelet immobilized surface in the reconstituted blood at a low platelet concentration ([platelet] = 5.0 x 10(4)/microL, a 5-fold diluted platelet concentration), and the attachment was suppressed by the addition of anti-GPIIb/IIIa monoclonal antibodies. It was confirmed that fibrinogen-albumin polymers specifically interacted with GPIIb/IIIa expressed on the surface of the activated platelets. Although platelets with a low platelet concentration were hardly attached to the platelet-immobilized surface under the flow conditions, the addition of fibrinogen-albumin polymers enhanced the attachment of the remaining platelets to the surface, indicating that the fibrinogen-albumin polymers would help the hemostatic ability of platelets at the site of vascular injury of patients in thrombocytopenia. PMID- 11777393 TI - Preparation of chitosan gel beads by ionotropic molybdate gelation. AB - A new process is described for the preparation of chitosan gel beads using molybdate as the gelling agent. This new gelation technique leads to a structure different from that produced during alkaline coagulation of a chitosan solution. Instead of a morphology characterized by large open pores, gel beads produced in a molybdate solution, under optimum conditions (pH 6; molybdate concentration, 7 g x L(-1)), have a double layer structure corresponding to a very compact 100 microm thick external layer and an internal structure of small pores. Experimental conditions, especially pH and molybdate concentration, were selected to optimize molybdate content and the stability of the bead shape. PMID- 11777394 TI - Silyl ether-coupled poly(epsilon-caprolactone)s with stepwise hydrolytic degradation profiles. AB - Silyl ether-coupled poly(epsilon-caprolactone)s (PCLs) with stepwise degradation profiles were synthesized via the cross-dehydrocoupling polymerizations between 1,4-bis(dimethylsilyl)benzene (BDSB) and telechelic, diol-terminated PCL macromonomers. With the presence of 10 wt % palladium on activated carbon as the catalyst, the condensations between BDSB and diol-terminated PCL macromonomers having molecular weights of 1200, 2010, and 5500 g/mol were performed in toluene at 100 degrees C under argon. Hydrogen was eliminated as the condensate upon the formation of silyl ether bonds linking the PCL blocks, yielding within 24 h, silyl ether-coupled PCLs of molecular mass 7590, 29,900, and 29,500 g/mol, respectively. The characterization of each polymer included (1)H NMR, (13)C NMR, and (29)Si NMR spectroscopies, size exclusion chromatography (SEC), and differential scanning calorimetry. The hydrolytic degradation properties of the polymers in solution were studied, and the molecular weight reductions over time were monitored by SEC. The silyl ether linkages of the polymers underwent hydrolysis in the presence of mineral acids, whereas the PCL segments released from the cleavage of the labile silyl ether coupling unit did not undergo detectable molecular weight reduction over 15 days. In the presence of acetic acid, the silyl ether functionalities were cleaved with a half-life of 3 days; however, the PCL chain required reaction with trifluoroacetic acid to give a number-average molecular weight loss half-life of 4 days. The silyl ether-coupled PCLs underwent degradation in a gradient fashion, therefore, by a protocol that involved the addition of acetic acid for cleavage of the silyl ether functionalities, followed by further addition of trifluoroacetic acid to bring the hydrolysis of the silyl ether functionalities to completion and to trigger the degradation of PCL segments. PMID- 11777395 TI - Synthesis of paucidisperse poly(gamma-benzyl-alpha,L-glutamate) oligomers and star polymers with rigid arms. AB - The synthesis of highly uniform gamma-benzyl-alpha,L-glutamate (BLG) oligomers via a convergent solution phase approach is reported. BLG oligomers were produced with designed lengths of 4, 8, 12, and 16 as a first step to production of BLG-4 mer and BLG-8-mer rod stars. The star oligomers were purified by size-exclusion chromatography and reversed phase HPLC, and characterized by MALDI-TOF mass spectrometry and reversed phase HPLC. These star-shaped BLG oligomers could be used as initiators for growing larger stars. PMID- 11777396 TI - Allosterically controllable maxizyme-mediated suppression of progression of leukemia in mice. AB - Chronic myelogenous leukemia (CML) is a hematopoietic malignant disease associated with expression of a chimeric BCR-ABL gene. We recently succeeded in designing a novel allosterically controllable ribozyme, the maxizyme (Tanabe et al. Biomacromolecules 2000, 1, 108-117; Kuwabara et al. Biomacromolecules 2001, 2, 788-799), that not only specifically cleaves BCR-ABL mRNA and induces apoptosis in cultured CML cells but also shows significant inhibition against the growth of an established BV173 cell line in a mouse model (Tanabe et al. Nature 2000, 406, 473-474). As an extension of our studies, we tested the maxizyme against primary CML cells in the same mouse model. The maxizyme under the control of a tRNA(Val) promoter showed significant inhibition against the growth of the primary bone marrow cells from a Japanese patient with CML. Specifically, to examine the applicability of the maxizyme in the treatment of CML, we assessed the antitumor effect of the maxizyme in murine models of CML. Fourteen weeks after the injection of primary CML cells into a NOD-SCID mouse, the bone marrow of the mouse was filled with primary CML cells as a result of diffuse leukemia. In marked contrast, when maxizyme-expressing primary CML cells were injected, the mouse remained disease-free. These results further strengthen our earlier suggestion that the maxizyme technology might provide a useful approach to the treatment of CML. PMID- 11777397 TI - Recognition of engineered tRNAs with an extended 3' end by Exportin-t (Xpo-t) and transport of tRNA-attached ribozymes to the cytoplasm in somatic cells. AB - Our recent analysis indicates that the cytoplasmic localization of tRNA-attached ribozymes (tRNA-Rz) is critical for its high-level intracellular activity, suggesting that mature mRNAs in the cytoplasm are more accessible to ribozymes than pre-mRNAs in the nucleus (Kato et al. J. Biol. Chem. 2001, 276, 15378-15385; Kuwabara et al. Nucleic Acids Res. 2001, 29, 2780-2788). Although studies in Xenopus oocytes led to the proposal that only correctly processed mature tRNAs are exported from nuclei in a RanGTP-dependent manner (Lund and Dahlberg Science 1998, 282, 2082-2085), our tRNA-Rz with an extended 3' end can also be exported to the cytoplasm in somatic cells. Xpo-t/RanGTP bound to tRNA-attached ribozymes in vitro and in somatic cells, with recognition basically resembling the recognition of mature tRNAs. In contrast, no binding to tRNA-attached ribozymes occurred in Xenopus oocytes. The injection of a nuclear extract of Xenopus oocytes together with tRNA-attached ribozymes inhibited the export of tRNA attached ribozymes but not mature tRNAs in somatic cells, suggesting the existence of an inhibitor(s) of the Xpo-t-dependent export pathway. Moreover, the inhibitor(s) appears responsible for a proofreading mechanism that operates in oocytes. PMID- 11777398 TI - Use of iron monocarboxylates in the two-step preparation of poly(ester urethane)s. AB - Five different iron monocarboxylates were used as catalysts in the two-step preparation route of lactic acid based poly(ester-urethane)s (PEU). In the first step, a hydroxyl-terminated poly(lactic acid) prepolymer was prepared, which in the second step was linked with 1,6-hexamethylene diisocyanate. The resulting polymers were characterized by titration, size exclusion chromatography, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy, and the mechanical properties were tested as well. Iron monocarboxylates proved to be efficient catalysts in the preparation of a hydroxyl-terminated prepolymer (lowest acid number obtained: 0.08). The same catalyst systems proved also to be highly efficient in the linking step yielding a high molar mass PEU. Semicrystalline PEUs could be prepared at 160 and 180 degrees C by using the iron acetate of different oxidation state. PEU prepared at 200 degrees C was amorphous, which could be related to racemization during the polycondensation. By using the fluorinated iron acetate amorphous PEUs was prepared at all reaction temperatures. The molar mass of the prepolymers and the PEUs increased as a function of the polycondensation temperature for all catalysts used. The highest weight-average molar masses (M(w)) were obtained by using the fluorinated iron acetate. PMID- 11777399 TI - Characterization and biocompatibility studies of novel humic acids based films as membrane material for an implantable glucose sensor. AB - Multilayered films of humic acids (HAs) (naturally occurring biopolymers) were investigated as a potential semipermeable membrane for implantable glucose sensors. These films were grown using a layer-by-layer self-assembly process of HAs and oppositely charged ferric ions. The growth of these assemblies exhibited strong dependence on the pH and ionic strength of HAs solutions, which correlated with the degree of ionization of the carboxyl groups and neutralization-induced surface spreading. Quartz crystal microbalance (QCM) and ellipsometric studies have shown repeatable, stepwise increase in mass (as high as 5.63 microg/cm(2)) and in film thickness (ca. 24.3 nm per layer) for these assemblies. The permeability of glucose through these membranes can be regulated by varying the number of self-assembled HAs/Fe(3+) layers. Moreover, a 200 nm thick HAs/Fe(3+) film (in its hydrated state) had a shear modulus of about 80 MPa, implying stability upon implantation. These films were determined to be biocompatible since in vivo studies indicated only mild tissue reaction along with some neovascularization. PMID- 11777400 TI - Polymeric surfactants based on inulin, a polysaccharide extracted from chicory. 1. Synthesis and interfacial properties. AB - Inulin, the polydisperse reserve polysaccharide from chicory, has been modified by carbamoylation in organic solvents. The reaction of inulin with a range of alkyl isocyanates resulted, after crystalization, in a variety of carbamoylated inulins from which the interfacial properties were determined. The medium and long chain carbamoylated inulins showed a good to very good reduction of the interfacial tension which makes these biopolymers interesting in the field of biodegradable surface active agents. PMID- 11777401 TI - Compatibilization of starch-allylurea blends by electron beam irradiation: spectroscopic monitoring and assessment of grafting efficiency. AB - The chemical changes induced by electron-beam irradiation of mixtures of N allylurea (AU) and amorphized starch were studied by spectroscopic methods for identifying and monitoring the reactions providing the blend with stabilized physical properties. Spectral modifications essentially concerned the AU constituent in the irradiated mixtures. FTIR and NMR analyses were used to quantify the progress of AU conversion upon irradiation and to gain information on the structure of the products. The influence of sample temperature and moisture on AU conversion rate was examined. The kinetic treatment of conversion vs dose data, from blends with different contents in AU, suggested that the phenomenological order for the reaction rate was zero, relative to the concentration in AU. The grafting yield was determined from combined (1)H NMR data recorded after selective solubilization of the constituents allowing for extraction of AU monomer and homopolymer from the grafted polysaccharide. Graft polymerization was more efficient than homopolymerization in samples containing AU in amounts less than its limiting solubility and relatively less efficient in thermodynamically unstable blends. PMID- 11777402 TI - Convenient synthesis of aliphatic polyesters by distannoxane-catalyzed polycondensation. AB - A convenient synthesis of aliphatic polyesters by the distannoxane-catalyzed polycondensation of aliphatic dicarboxylic acids and aliphatic diols in solvents under azeotropic conditions was developed. To determine the optimum conditions for polycondensation of succinic acid with 1,4-butandiol, the effect of various types of catalyst and their concentration was investigated. By choosing the appropriate solvent, the polymerization was made to proceed in a two-phase system of solvent and molten polymer, and in the presence of 0.001 mol % of 1-chloro-3 hydroxy-1,1,3,3-tetrabutyldistannoxane (CHTD), poly(butylene succinate) (PBS) with a weight-average molecular weight of 277,000 was obtained. This method was then successfully applied to the synthesis of various aliphatic polyesters, such as poly(ethylene succinate), poly(1,4-cyclohexanedimethylene succinate), and poly(ethylene sebacate). PMID- 11777403 TI - Hydrophilic polymeric acylphospine oxide photoinitiators/crosslinkers for in vivo blue-light photopolymerization. AB - Three vinyl-functionalized phosphine oxide photoinitiating monomers have been synthesized: 4-vinylbenzoyldiphenylphosphine oxide (VBPO), 2,6-dimethyl-4 vinylbenzoyldiphenylphosphine oxide (DMVBPO), and 2,4,6-trimethylbenzoylphenyl-4 vinylphenylphosphine oxide (TMBVPO). VBPO was copolymerized with vinylpyrrolidone or vinyl acetate (PPI-1a) and dimethylacrylamide (PPI-1b). DMVBPO and TMBVPO were both copolymerized with dimethylacrylamide (PPI-2 and PPI-3, respectively). The choice of vinylphosphine oxide and comonomer(s) had a significant influence on the properties of the resulting PPI. PPI-1a was not stable in solution in 2 hydroxyethyl methacrylate (HEMA), whereas the VBPO-dimethylacrylamide (DMA) copolymer (PPI-1b) was stable in HEMA but not stable in aqueous solutions. PPI-2 was both soluble and stable in water up to 22 months. PPI-1a was as effective as trimethylbenzoyldiphenylphosphine oxide (TPO, BASF Lucirin). PPI-2 was more effective in the polymerization of HEMA/water mixtures than PPI-3. PPI-2 and PPI 3 acted as self-cross-linking species, resulting in the formation of hydrogels; PPI 3 was more effective in this. PPI-2 was very effective in forming hydrogels based on poly(ethylene glycol) diacrylate. PMID- 11777404 TI - Novel degradable polymers combining D-gluconic acid, a sugar of vegetal origin, with lactic and glycolic acids. AB - To synthesize functionalized poly(lactic acid-co-glycolic acid)-based polyesters for biomedical and pharmaceutical applications such as controlled drug delivery, D-gluconic acid was considered as an interesting source of comonomer. Accordingly D-gluconic acid was used to synthesize novel 1,4-dioxane-2,5-diones with protected hydroxyl groups, namely 3-(1,2:3,4-tetraoxobutyl-di-O-isopropylidene) dioxane-2,5-dione (5a) and 3-methyl-6-(1,2:3,4-tetraoxobutyl-di-O-isopropylidene) dioxane-2,5-dione (5b). The ring-opening homopolymerization and copolymerization of these cyclic dilactones with DL-lactide provided novel degradable polyesters with higher glass transition temperatures than poly(lactic acid-co-glycolic acid) polymers. PMID- 11777405 TI - Comonomer unit composition and thermal properties of poly(3-hydroxybutyrate-co-4 hydroxybutyrate)s biosynthesized by Ralstonia eutropha. AB - A series of poly(3-hydroxybutyrate-co-4-hydroxybutyrate)s [P(3HB-co-4HB)s] with different 4HB content, biosynthesized by Ralstonia eutropha H16 with mixed carbon sources of 4-hydroxybutyric acid (4HBA) and butyric acid, were fractionated by solvent/nonsolvent fractionation into copolyester fractions with different 4HB content and narrower compositional distribution. The fractions obtained were classified into two groups, 3HB- and 4HB-rich P(3HB-co-4HB)s. The thermal properties were investigated for these fractionated copolyesters. With increasing 4HB content, the melting temperature at first decreased while 3HB content was rich, and then increased while 4HB content was rich. The glass transition temperature decreased linearly with increasing 4HB content. The 4HB-rich P(3HB-co 4HB) was found to be immiscible with the 3HB-rich P(3HB-co-4HB), as two glass transitions corresponding to those of respective P(3HB-co-4HB)s were observed by DSC. It was concluded that as-produced bacterial P(3HB-co-4HB) samples used in this study should be considered as immiscible polymer blends. PMID- 11777406 TI - Physicochemical properties of physical chitin hydrogels: modeling and relation with the mechanical properties. AB - In this work, we were interested in the modeling of syneresis of physical chitin hydrogels by a mathematic law allowing us to predict the variation of the weight of the gel as a function of time. The variation of the weight of the gel during syneresis can be described by W(t)()/W(0) = (t(1/2) + (W(infinity)/W(0))t)/(t(1/2)) + t) where W(0), W(infinity), and W(t)() are the weights of the gel at the beginning of syneresis, for infinite time and for a time t, respectively. t(1/2) corresponds to the half-time of syneresis. W(infinity)/W(0) and t(1/2) were studied in relation with several parameters such as the ionic strength, pH, degree of acetylation of chitin and the initial concentration of polymer. The mechanical properties of chitin hydrogels maintained during syneresis in media of different pH's and ionic strengths were also investigated. PMID- 11777408 TI - Electrophoretic light scattering studies of chitosans with different degrees of N acetylation. AB - Electrostatic properties of three chitosans with fractions of N-acetylated units (F(A)) of 0.01, 0.13 and 0.49 were examined by electrophoretic light-scattering technique (ELS) and (1)H NMR spectroscopy. From the dependency of mean electrophoretic mobilities on pH, the pK(a) values were calculated. Despite their large differences in chemical composition, all chitosans had similar pK(a) values of 6.5-6.6. All chitosans also showed the same polyelectrolyte behavior when apparent pK(a) values were calculated according to Katchalsky and plotted as a function of the degree of ionization alpha. The intrinsic pK(a) values (pK(0)) extrapolated to zero charge were about 9. The results derived from an independent (1)H NMR study of the same chitosan samples showed no effect of F(A) on titration behavior of chitosan, confirming the results obtained by ELS. PMID- 11777407 TI - Pressure cell assisted solution characterization of polysaccharides. 1. Guar gum. AB - To reduce time-dependent aggregation phenomena and achieve true "molecular" solution, the "pressure cell" solubilization method of Vorwerg and co-workers was applied to solutions of guar galactomannans (three samples of different molecular weights), using various heating, time, and pressure profiles. Physicochemical characterization of the guar samples before and after pressure cell treatment included measurements of intrinsic viscosity [eta] by capillary viscometry and M(w) and radius of gyration from size exclusion chromatography coupled to multiangle laser light scattering (SEC/MALLS). Heating the guar solutions (100 160 degrees C) without pressurization produced chain degradation with [eta] and M(w) values being reduced significantly, whereas this effect was reduced substantially for samples subject to initial pressurization ( approximately 5-10 bar). The constants in the Mark-Houwink-Sakurada equation, relating [eta] and M(w) were established and the characteristic ratio C(infinity) and chain persistence length L(p) were calculated using both the Burchard-Stockmayer-Fixman (BSF) method for flexible and semiflexible chains and the Hearst method more appropriate for stiffened chains. Definitive conclusions can now be drawn on the flexibility of the guar chain backbone, with L(p) approximately 4 nm from the BSF plot, in good agreement with previously published work using such geometric methods. This contrasts with the higher values obtained from extrapolation of data for polyelectrolytes with a similar backbone geometry, such as sodium carboxymethyl cellulose, to "infinite" ionic strength. PMID- 11777409 TI - Comonomer compositional distribution and thermal and morphological characteristics of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate)s with high 3-hydroxyvalerate content. AB - The comonomer compositional distribution and thermal and morphological characteristics were investigated for five bacterially synthesized poly(3 hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] samples with 3HV content of 45, 49, 70, 80, and 96 mol %. All these samples were fractionated into many fractions with widely different 3HV content by changing solvent/nonsolvent volume ratio of chloroform/n-heptane mixtures. Bacterial P(3HB-co-3HV) samples investigated in this study were found to have broad comonomer compositional distribution. The tendencies of the fractional precipitation of the P((3HB-co 3HV)s with 3HV content lower than 60 mol % and those with 3HV higher than 80 mol % were found to be contrary. The 3HV content dependences of the thermal properties and crystalline structures were investigated for bacterial poly(3 hydroxybutyrate) [P(3HB)] and a series of compositionally well-fractionated P(3HB co-3HV) samples with 3HV content ranged from 14 to 98 mol % by DSC, WAXD, and solid-state (13)C NMR. It was found that P(3HB-co-3HV) samples with 3HV content lower than about 47 mol % form the crystalline lattice having the P(3HB) homopolymer type lattice including the 3HV unit as the crystal constituent, and those with a 3HV content higher than about 52 mol % form the crystalline lattice having the P(3HV) homopolymer type lattice including the 3HB units. Thus, P(3HB co-3HV)s show the crystalline structural change in a very narrow range of 3HV content. PMID- 11777410 TI - "Nematic ordered cellulose": a concept of glucan chain association. AB - Native cellulose consists of a set of parallel chains composed of glucose. Most of the time, these chains are highly ordered and form a structure that is known as a microfibril. On the other hand, highly crystalline forms of cellulose are more difficult to process and often are unpredictable in their behavior. If an ordered but noncrystalline form of cellulose could be produced, this would greatly extend the possibilities of usage of cellulose to new areas. In this paper, we have produced such a new supermolecular structure of cellulose, called nematic ordered cellulose. The unique characteristics of this supermolecular structure of cellulose have been clarified using various kinds of physicochemical analyses. Using a high-resolution transmission electron microscopic approach, we have also imaged the single glucan chains, demonstrating the close but nonprecise association usually found in crystalline biopolymers. PMID- 11777411 TI - Microstructure of aggregated and nonaggregated kappa-carrageenan helices visualized by atomic force microscopy. AB - Gelation of kappa-carrageenan is believed to involve two steps: helix formation on cooling and a further specific cation (salt) induced side-by-side aggregation of helices. Samples that should contain aggregated and also nonaggregated "helices" of kappa-carrageenan were prepared in aqueous solutions, spread onto freshly cleaved mica surfaces, and visualized under butanol using atomic force microscopy. In the presence of an excessive amount of a gel-promoting salt, KCl, kappa-carrageenan appeared to form rigid rodlike structures considered as large aggregates of double helices. Even when the side-by-side interhelical aggregation was suppressed by diluting random coiled solutions prior to cooling, by adding an aggregation-impeding salt, NaI, or by transforming kappa-carrageenan into the tetramethylammonium (TMA) salt, branched rodlike structures were still evident, suggesting that the side-by-side aggregation of helices is not a prerequisite for kappa-carrageenan to form a network structure, at least locally. Even in the absence of factors that promote side-by-side aggregation, kappa-carrageenan helices appeared to be capable of associating and forming gel networks. PMID- 11777413 TI - Graft copolymer having hydrophobic backbone and hydrophilic branches. 33. Interaction of hepatocytes and polystyrene nanospheres having lactose-immobilized hydrophilic polymers on their surfaces. PMID- 11777412 TI - Heterologous expression of cyanophycin synthetase and cyanophycin synthesis in the industrial relevant bacteria Corynebacterium glutamicum and Ralstonia eutropha and in Pseudomonas putida. PMID- 11777415 TI - Photochromism: Memories and Switches-Introduction. PMID- 11777416 TI - Diarylethenes for Memories and Switches. PMID- 11777414 TI - Synthesis of amphiphilic poly(epsilon-caprolactone) macromonomers by lipase catalysis. PMID- 11777417 TI - Fulgides for Memories and Switches. PMID- 11777419 TI - Bacteriorhodopsin as a Photochromic Retinal Protein for Optical Memories. PMID- 11777418 TI - Spiropyrans and Spirooxazines for Memories and Switches. PMID- 11777420 TI - Three-Dimensional Optical Data Storage Using Photochromic Materials. PMID- 11777421 TI - Chiroptical Molecular Switches. PMID- 11777422 TI - Linear and Nonlinear Optical Properties of Photochromic Molecules and Materials. PMID- 11777423 TI - Photoalignment of Liquid-Crystal Systems. PMID- 11777424 TI - Ultrafast Dynamics of Photochromic Systems. PMID- 11777425 TI - Coenzyme A Analogues and Derivatives: Synthesis and Applications as Mechanistic Probes of Coenzyme A Ester-Utilizing Enzymes. PMID- 11777426 TI - Methodologies for Generating Solution-Phase Combinatorial Libraries. PMID- 11777427 TI - Silylphosphanes: Developments in Phosphorus Chemistry. PMID- 11777428 TI - Phase Transitions of Aqueous Atmospheric Particles. PMID- 11777429 TI - Synthesis of Strychnine. PMID- 11777430 TI - New Self-Assembled Structural Motifs in Coordination Chemistry. PMID- 11777431 TI - New Self-Assembled Structural Motifs in Coordination Chemistry (Chem. Rev. 2000, 100, xxxx. Published on the Web July 15, 2000.). PMID- 11777433 TI - Transition-metal-catalyzed reactions of propargylamine with carbon dioxide and carbon disulfide. AB - The reactions of propargylamine derivatives with carbon dioxide and carbon disulfide have been systematically examined in the presence of transition-metal catalysts. Pd(OAc)(2) is the best catalyst for the formation of the corresponding oxazolidinones. In addition, we found that, in the reaction of propargylamine with carbon dioxide catalyzed by palladium(0) metal catalyst in toluene, both oxazolidinone 1 and imidazolidinone 2 could be obtained under mild reaction conditions at the same time. The reaction of 1 with primary and secondary amines has been examined. A plausible reaction mechanism for the formation of 2 was proposed. In addition, in this paper, we first disclosed the ligand's effect on this reaction. Using PBu(t)(3) as a ligand with Pd(2)(dba)(3), 1 was exclusively formed in 90% yield. PMID- 11777432 TI - Universal solid-phase approach for the immobilization, derivatization, and resin to-resin transfer reactions of boronic acids. AB - Boronic acid-containing molecules are employed in a broad range of biological, medicinal, and synthetic applications. These compounds, however, tend to be difficult to handle by solution-phase methods. Herein, this problem is addressed with the development of the first general solid-phase approach for the derivatization of functionalized boronic acids. This approach is based on the use of a diethanolamine resin anchor that facilitates boronic acid immobilization by avoiding the need for exhaustive removal of water in the esterification process. The immobilization of a wide variety of boronic acids onto N,N diethanolaminomethyl polystyrene (DEAM-PS, 1) can be performed within minutes by simple stirring in anhydrous solvents at room temperature. Evidence for the formation of a bicyclic diethanolamine boronate with putative N-B coordination was shown by (1)H NMR analysis of DEAM-PS-supported p-tolylboronic acid. The hydrolytic cleavage of the same model boronic acid from the DEAM-PS resin was studied by UV spectroscopy. Hydrolysis and attachment were shown to occur under a rapidly attained equilibrium, and a large excess of water (>32 equiv) is required to effect a practically quantitative release of boronic acids from DEAM-PS. Despite their relative sensitivity to water and alcohols, DEAM-PS-bound arylboronic acids functionalized with a formyl, a bromomethyl, a carboxyl, or an amino group can be transformed in good to excellent yields into a wide variety of amines, amides, anilides, and ureas, respectively. Ugi multicomponent reactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctional arylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin to-resin transfer reactions (RRTR). This type of multiresin process helps eliminate time-consuming cleavage and transfer operations, thereby considerably simplifying the outlook of combinatorial library synthesis by manual or automated means. This concept was illustrated by a set of optimized procedures for the Suzuki cross-coupling and the borono-Mannich reactions. PMID- 11777434 TI - Diasteroselective cyclizations with enantiopure malonaldehyde monocycloacetals. AB - The synthesis of a series of enantiopure malonaldehyde monocycloacetals is described. Treatment of 8b with L-tryptophan methyl ester, 5-methoxytryptamine, and tryptamine, respectively, in the Pictet-Spengler condensation gave the corresponding enantiomerically pure key precursors 1-3 and 17-21 in only two steps. Using a chiral amino-diol successfully realized the kinetic resolution of racemic carbolines 23 and 24. PMID- 11777435 TI - NMR and X-ray crystallographic studies of the conformation of a 3,4,6-triphenyl delta-lactone. AB - 1-Oxa-3S,4S,6R-triphenyl-2-cyclohexanone and its enantiomer were synthesized, and the structure was determined by NMR and X-ray crystallography. The X-ray crystal structure showed that the delta-lactone adopts a boat conformation in the solid. The X-ray data showed a shortened C-O bond between the carbonyl carbon and the ether oxygen, consistent with delocalization involving the ester group. (1)H and (13)C NMR measurements in acetone-d(6) showed that the lactone is biased in favor of a boat conformation. In the less polar solvent chloroform-d(1), changes in the (1)H NMR coupling constants indicate a shift in the equilibrium in favor of a less rigid twist-boat conformation. The IR absorption of the lactone carbonyl at 1740 cm(-)(1) would suggest a half-chair conformation inconsistent with the dominance of the boat forms shown by NMR and X-ray. PMID- 11777436 TI - Synthesis of 2,3-disubstituted pyrroles from 3,N-dilithio-N-(tert butyldimethylsilyl)-2-buten-1-amine. AB - N-(Trialkylsilyl)allylamines can be deprotonated at the cis-vinylic position to yield 3,N-dilithio-N-(trialkylsilyl)allylamines under mild conditions. N (Trialkylsilyl)allylamines with terminal alkyl substituents were reported not to form dianions under the same conditions. During our investigations we found that N-(tert-butyldimethylsilyl)-2-buten-1-amine (1) is deprotonated under the reaction conditions reported in the literature, but the resulting dianion is quenched by ethereal solvents. Consequently, new reaction conditions were developed that allow the generation of stable dianions from allylamines with terminal alkyl substituents. Thus, 2,3-disubstituted pyrroles hitherto unattainable via this methodology were formed from 3,N-dilithio-N-(tert butyldimethylsilyl)-2-buten-1-amine (2) and various carbonyl electrophiles in good yields. PMID- 11777437 TI - Structure of 1-(arylselanyl)naphthalenes. 2. G dependence in 8-G-1-(p YC(6)H(4)Se)C(10)H(6). AB - The structures of 8-G-1-(p-YC(6)H(4)Se)C(10)H(6) (1 (G = Cl) and 2 (G = Br): Y = H (a), OMe (b), Me (c), Cl (d), Br (e), COOEt (f), and NO(2) (g)) were investigated by X-ray crystallographic analysis, NMR spectroscopy, and ab initio MO calculations. The structures of all members in 1 and 2 are concluded to be type B, which is in striking contrast to the type A structure for 4d-g (4 (g(n)), where G = H). The Se-C(i) bond of the p-YC(6)H(4)Se group in 8-G-1-(p YC(6)H(4)Se)C(10)H(6) is almost perpendicular to the naphthyl plane in type A, and it is located on the plane in type B. The chlorine and bromine substitution at the 8-position in 1 and 2 dramatically changes the type A structure of 4 (g(n)) to type B. The nonbonded G- - -Se-C 3c-4e type interaction must contribute to stabilize the type B structure. The type B structure in 1 and 2 should also be more stabilized than the same structure in 4 by the 3c-4e type interaction: The structure of 4b is type B in the crystals and type B would be more stable for 4c and might be for 4a in solutions. Ab initio MO calculations are performed on 8-G 1-(p-YC(6)H(4)Se)C(10)H(6), 8-G-C(10)H(6)SeH-1, and models HG- - -SeH(2), where G = Cl, Br, and F, to clarify the reason for the dramatic change in the structures. The type B structure is optimized to be more stable than the type A for all species examined, which supports the observations. The energy differences between type B and type A are larger for the models than for the naphthalenes. While the superiority of the type B for the former is Br > Cl >> F, that of the latter is Br approximately Cl >/= F. These results show that the main factor of the structural change from type A to type B is the nonbonded G- - -Se-C 3c-4e interaction. The electronic effect of halogens through the naphthalene pi framework would also contribute to some extent, although the direct comparison of the evaluated values between the naphthalene systems and the models is not so easy. Factors to stabilize the two structures of 1, 2, 4, and 8-(MeSe)-1-(p YC(6)H(4)Se)C(10)H(6) are reexamined from a viewpoint of the nonbonded G- - -Se-C 3c-4e interaction (G dependence), together with the electronic effect of Y (Y dependence). PMID- 11777438 TI - Regio- and stereoisomeric control of the aggregation of zinc-chlorins possessing inverted interactive hydroxyl and carbonyl groups. AB - As models for a self-aggregative, naturally occurring magnesium-chlorin bacteriochlorophyll-d possessing 3(1)-secondary alcoholic hydroxyl and 13(1)-oxo groups, zinc-chlorins were synthesized with 3(1)-oxo and 13(1)-secondary (1) or tertiary hydroxyl groups (2). Compared to the monomers in a tetrahydrofuran solution, diastereomers 13(1)R-1R and 13(1)S-1S gave red-shifted absorption maxima (643 --> 674 nm in 1R and 708 nm in 1S) in 1 v/v% CH(2)Cl(2)-hexane solution, indicating their self-aggregation. Therefore, the positioning of the two groups at 3(1)/13(1) or 13(1)/3(1) on the N21-N23 molecular (Q(y)) axis is not necessarily important for the self-aggregation. The (1)H NMR and CD spectroscopic studies showed that the 674 nm absorbing species of 1R was characterized as a face-to-face "closed" dimer, while the 708 nm absorbing species of 1S was a large oligomer constructed with aggregation of head-to-tail "open" dimers. This diastereomeric control over the aggregation of 1R and 1S is more pronounced than that observed in the regioisomerically 3(1)-secondary alcoholic R/S-diastereomers 3R and 3S. The difference is ascribable to the conformational fixation of the 13(1)-hydroxyl group of the exo five-membered ring in 1. In contrast to self-aggregative 3(1)-tertiary alcoholic 4, both 13(1) epimers of 13(1)-tertiary alcoholic 2 were monomeric even in nonpolar organic media: the additional 13(1)-methyl group (1 --> 2) drastically suppressed the self-aggregation due to the interference of the methyl group in intermolecular pi pi interaction. PMID- 11777439 TI - Synthesis and mass spectrometry studies of branched oxime ether libraries. Mapping the substitution motif via linker stability and fragmentation pattern. AB - The oxime ether chemistry has recently been used as a convenient approach to preparing potentially highly diverse combinatorial libraries. The synthetically easiest way to form the libraries is convergent, i.e., via reaction of a branched scaffold containing two or more aminooxy linker groups, with a variety of carbonyl substituents. We show here that such reactions between aldehydes and ketones of different structure with the scaffolds containing different types of aminooxy groups can lead to the formation of virtually all expected components in the model mixtures 1-3 formed from three scaffolds (7-9) and eight substituents (R(1)-R(8)). One important problem with the branched libraries is that the libraries formed from the more complex scaffolds, such as 11, contain multiple regioisomers. The results of extensive analysis of a variety of library components by mass spectrometry presented here show that the differences in the MS-MS fragmentation energies for different linkers yield regiochemical information essential for identification of individual library components. PMID- 11777440 TI - Reactivity of 2-halo-2H-azirines. 1. Reactions with nucleophiles. AB - Nucleophilic substitution reactions of 2-halo-2H-azirines 1a, 1b, 1d, and 1e with potassium phthalimide and aniline allowed the preparation of new substituted 2H azirines 2-5. The reactions of 2-bromo-2H-azirine 1a with methylamine led to the synthesis of alpha-diimines 7 and 8. 2-Halo-2H-azirines were also established as building blocks for the synthesis of a range of heterocyclic compounds, namely, quinoxalines 10a-10d, 3-oxazoline 14, and 2H-[1,4]oxazines 18 and 20. X-ray crystal structures of alpha-diimine 7, 3-oxazoline 14, and 2H-[1,4]oxazine 18 are reported. PMID- 11777441 TI - Catalyzed Reformatsky reactions with ethyl bromofluoroacetate for the synthesis of alpha-fluoro-beta-hydroxy acids. AB - The presence of catalytic amounts of CeCl(3) improves yields and simplifies procedure in the Reformatsky reactions of ethyl bromofluoroacetate with aldehydes and ketones to generate diastereomeric mixtures of alpha-fluoro-beta-hydroxy esters, some of which can be separated by crystallization or column flash chromatography. Diastereomerically pure alpha-fluoro-beta-hydroxy acids are obtained by mild alkaline hydrolysis of the resolved alpha-fluoro-beta-hydroxy esters. Detailed NMR data of new alpha-fluoro-beta-hydroxy esters and alpha fluoro-beta-hydroxy acids are also presented. PMID- 11777442 TI - Nickel-catalyzed cross-coupling between functionalized primary or secondary alkylzinc halides and primary alkyl halides. AB - In the presence of Bu(4)NI (3 equiv) and 4-fluorostyrene (20 mol %), unreactive primary and secondary alkylzinc iodides undergo nickel-catalyzed cross-couplings with various primary alkyl iodides or bromides. More reactive secondary dialkylzincs and the mixed zinc organometallics RZnTMSM undergo the cross coupling reaction in the absence of Bu(4)NI. The bicyclic secondary diorganozinc 6 prepared via boron-zinc exchange reacts with high retention of configuration. Free NH-groups are tolerated in the cross-coupling allowing the synthesis of aminated products. PMID- 11777443 TI - Synthesis of isoquinolines and pyridines by the palladium/copper-catalyzed coupling and cyclization of terminal acetylenes and unsaturated imines: the total synthesis of decumbenine B. AB - Monosubstituted isoquinolines and pyridines have been prepared in good to excellent yields via coupling of terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the intermediate iminoalkynes. In addition, isoquinoline heterocycles have been prepared in excellent yields via copper-catalyzed cyclization of iminoalkynes. The choice of cyclization conditions is dependent upon the nature of the terminal acetylene that is employed, as only aryl and alkenyl acetylenes cyclize under the palladium catalyzed reaction conditions that have been developed. However, aryl-, vinylic-, and alkyl-substituted acetylenes undergo palladium-catalyzed coupling and subsequent copper-catalyzed cyclization in excellent yields. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling and cyclization methodology. PMID- 11777444 TI - Efficient synthesis of 2-mono- and 2,5-disubstituted furans via the CuI-catalyzed cycloisomerization of alkynyl ketones. AB - A mild, general, and efficient method for the synthesis of 2-monosubstituted and 2,5-disubstituted furans via the CuI-catalyzed cycloisomerization of alkynyl ketones was developed. It was demonstrated that furans containing both acid- and base-labile groups could be easily synthesized using this methodology. A plausible mechanism for this transformation is proposed. PMID- 11777445 TI - Palladium-catalyzed three-component assembling of allenes, organic halides, and arylboronic acids. AB - An efficient method for the construction of two carbon-carbon bonds in a regio- and stereoselective fashion via palladium-catalyzed assembling of allenes, organic halides, and arylboronic acids is described. Organic halides (RI = C(6)H(5)I, o-, m-, and p-CH(3)OC(6)H(4)I, p-C(2)H(5)OCOC(6)H(4)I, p CH(3)COC(6)H(4)I, p-CH(3)C(6)H(4)I, p-CH(3)C(6)H(4)Br, p-CH(3)C(6)H(4)Cl, p NO(2)C(6)H(4)I, p-NO(2)C(6)H(4)Br, p-NO(2)C(6)H(4)Cl, p-IC(6)H(4)Cl, 1 iodonaphthalene, 2-iodothiophene, 3-iodo-2-cyclopenten-1-one, 3-iodo-5,5-dimethyl 2-cyclohexen-1-one, C(6)Eta(5)(Br)C=CH(2) and ICH(2)CO(2)C(2)H(5)), and arylboronic acids (ArB(OH)(2), Ar = C(6)H(5), p-CH(3)OC(6)H(4), m-NO(2)C(6)H(4), p-FC(6)H(4), 1-C(10)H(7), and o-, m-, and p-CHOC(6)H(4)) undergo Suzuki-type three-component assembling with 1,1-dimethylallene to give the corresponding allylic derivatives, (CH(3))(2)=CRCH(2)Ar, in DMF at 70 degrees C in the presence of CsF using Pd(dba)(2) as the catalyst. Higher yields of products were obtained for aryl iodides than for the corresponding aryl bromides and chlorides. This three-component assembling is highly regioselective, with the organic group on halides adding to the middle carbon and the aryl group on arylboronic acids to the unsubstituted terminal carbon of allenes. Monosubstituted allenes 1b-e (cyclopentylallene, cyclohexylallene, tert-butylallene, and n-butylallene) also undergo similar assembling reaction with organic halides and arylboronic acids to afford the corresponding products 7a-i with high regio- and stereoselectivity. Based on the known palladium chemistry, a mechanism is proposed to account for the catalytic reaction and the stereochemistry. PMID- 11777446 TI - Palladium-catalyzed monoarylation of nitroalkanes. AB - A general protocol for the Pd-catalyzed-arylation of nitroalkanes is described. Substituted aryl bromides as well as aryl chlorides can be coupled efficiently with a variety of nitroalkanes under mild conditions to selectively yield the monoarylated products. This method tolerates a number of functional groups including ketones, esters, and olefins. Notably, the arylation of nitroalkanes can be effected chemoselectively over ketone and ester arylation. PMID- 11777447 TI - beta-Silylcarbenes from isolable diazosilanes. AB - Manganese dioxide oxidation of the hydrazone derivative of tert butyldimethylsilyl acetophenone gave 2-tert-butyldimethylsilyl-1 phenyldiazoethane (17) an isolable diazocompound. Thermal and Rh(II)-catalyzed decomposition of diazosilane 17 in cyclohexane led to 1-tert-butyldimethylsilyl-1 phenylethylene (19) as the major product. The formation of alkene 19 presumably involves (tert-butyldimethylsilyl)methylphenylcarbene (21), which undergoes preferential 1,2-silyl migration as opposed to 1,2-hydrogen migration. Thermal decomposition of 17 in cyclohexane under oxygen gave substantial amounts of tert butyldimethylsilyl acetophenone, presumably by reaction of the intermediate carbene with oxygen. Thermal decomposition of 17 in methanol led to alkene 19 and 2-tert-butyldimethylsilyl-1-methoxy-1-phenylethane (22) as major products, along with a significant amount of trans-1-tert-butyldimethylsilyl-2-phenylethylene (20). Kinetic studies indicate that these products are not derived from acid catalyzed decomposition of the diazocompound 17. Formation of the methyl ether product 22 suggests the involvement of a beta-silyl carbocation intermediate, and solvent isotope effect studies indicate that this cation is at least partially derived from protonation of diazocompound 17 by neutral methanol. Photochemical decomposition of 17 in methanol produced the alkene 19 (97%) along with a small amount (2.4%) of the methyl ether 22. Capture of a photochemically generated carbene 21 by methanol is the proposed origin of this minor product. Geometry optimization of trimethylsilylmethylphenylcarbene (8) and carbene 21 at the HF/6 31G computational level led to a conformation consistent with a hyperconjugative interaction between the vacant p-orbital of these carbenes and the adjacent C-Si bond. Carbenes 8 and 21 are not energy minima at the B3LYP/6-31G level, where they rearrange to alkenes without barrier via silyl migration. These theoretical findings contrast with the proposed trapping of carbene 21 by methanol and oxygen. PMID- 11777448 TI - Pyrolysis of p-benzosemiquinone. AB - In contrast to the thermolysis of p-benzoquinone, which does not decompose until the temperature is over 800 degrees C, and then primarily yields vinylacetylene, the corresponding anion radical, precipitated from liquid ammonia [Na(+)(NH(3))C(6)H(4)O(2)(*-)], decomposes at 380 degrees C and fragments primarily into phenol, hydroquinone, ammonia, methane, carbon monoxide, hydrogen, and minor amounts of other simple compounds. When the benzoquinone is replaced with perdeuteriobenzoquinone, deuterium and hydrogen are randomly scrambled into the products, and both ND(3) and CH(4) are formed. When the hot pyrolysis container is completely sealed, preventing the escape of volatile materials, p aminophenol, as opposed to phenol, is the major liquid product. PMID- 11777449 TI - Highly E-selective and effective synthesis of antiarthritic drug candidate S-2474 using quinone methide derivatives. AB - We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2 isothiazolidine-1,1-dioxide (S-2474; 1), in which alpha-methoxy-p-quinone methide is used as a key intermediate. alpha-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with alpha-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed. PMID- 11777451 TI - The versatility of alpha-chloropropargyl phenyl sulfide affords high stereo- and regioselectivities in indium-promoted coupling reactions under mild conditions. AB - Coupling reactions between alpha-chloropropargyl phenyl sulfide (11) and a series of aldehydes under aqueous conditions are reported. Not only is good stereoselectivity observed between syn and anti isomeric products, but excellent regioselectivity is also witnessed. In reactions using indium metal as a promoter, the propargyl functionality (12) is retained, unlike the use of more traditional metals that result in formation of products containing a mixture of both propargyl (12) and allene (13) moieties. The reaction is postulated to proceed via either a chelated or nonchelated route, controlled by the presence or absence of indium (III) chloride, and may be used to create synthetically useful building blocks. The formation of epoxyalkyne (14) molecules, which are found in many natural products and have wide use as synthetic templates, is presented as one example. PMID- 11777450 TI - Practical synthesis of a dithiane-protected 3',5'-dialkoxybenzoin photolabile safety-catch linker for solid-phase organic synthesis. AB - The solution-phase preparation of the 3',5'-dialkoxybenzoin photolabile safety catch linker 16 is described. Pivotal to this convenient synthesis is the selection of appropriate orthogonal protecting groups for the alkoxy functionalities present. The new linker can be readily loaded onto any standard amine-terminating resin under peptide-coupling conditions, without the need to protect the secondary alcohol functionality, and subsequently loaded with substrate. Alternatively, the loading efficiency of sterically hindered substrates can be enhanced by preloading the semiprotected linker variant 10 in solution prior to immobilization onto the resin. This second generation of benzoin photolabile safety-catch linkers provides greater control of both linker loading and resin attachment and should prove to be a more versatile and convenient form of the linker. PMID- 11777452 TI - Synthesis of enzymatically and chemically non-hydrolyzable analogues of dinucleoside triphosphates Ap(3)A and Gp(3)G. AB - Dinucleoside polyphosphates are ubiquitous compounds tightly involved in the regulation of a number of key biological processes. Hydrolysis-resistant analogues of Ap(3)A and Gp(3)G, two important members of that family of nucleotides, have been synthesized. P(1),P(2):P(2),P(3)-Bis-methylene diadenosine and diguanosine triphosphates were prepared from O,O-dialkyl methaneselenophosphonates using an original methodology. Whereas the 2-fold addition of the methanephosphonate anion to the activated phosphorus species cannot be performed, multiple condensation of lithiated methaneselenophosphonate with electrophilic trivalent phosphorus compounds is revealed to be very effective. A one-pot condensation/esterification/oxidation sequence involving O,O dialkyl methaneselenophosphonates provides a highly efficient route to the PCH(2)PCH(2)P backbone. This new development in selenophosphonate chemistry offers a great potential for further regioselective functionalization of polyphosphate mimics. PMID- 11777453 TI - A density functional theory investigation of the Simmons-Smith cyclopropanation reaction: examination of the insertion reaction of zinc into the C-I bond of CH(2)I(2) and subsequent cyclopropanation reactions. AB - The insertion reaction of zinc into the C-I bond of CH(2)I(2) and subsequent cyclopropanation reactions with CH(2)CH(2) have been investigated using B3LYP level density functional theory calculations. The Simmons-Smith cyclopropanation reaction of olefins does not proceed easily due to the relatively large barriers on the insertion and cyclopropanation pathways. The computed results indicate that the IZnCH(2)I molecule is the active reagent in the Simmons-Smith reaction. This is consistent with the IZnCH(2)I reactive species being generated from diiodomethane and a Zn-Cu couple as proposed by several other research groups. The Simmons-Smith IZnCH(2)I carbenoid and CH(2)I-I carbenoid cyclopropanation reactions with olefins are compared. The reactions of olefins with the radicals from the decomposition of the IZnCH(2)I and CH(2)I-I species were also compared. We found that the chemical reactivity of the carbenoid species is dependent on its electrophilic behavior, steric effects, the leaving group character and the mechanism of the cyclopropanation reactions. PMID- 11777454 TI - (3R,4S)-4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine: conformation and structure monitoring by vibrational circular dichroism. AB - Absorption and vibrational circular dichroism (VCD) spectra of the title compound, a common intermediate in synthesis of many pharmaceuticals, were measured and analyzed in order to determine its absolute configuration and prevailing conformations. The analysis was combined with a systematic conformer search based on relative energies as well as with comparison of experimental and computed NMR shifts. The spectra were interpreted on the basis of ab initio simulations. The results indicate that the compound adopts exclusively a chair conformation of the piperidine ring with all the fluorophenyl, hydroxymethyl, and methyl substituents attached in equatorial positions. A limited rotation of the hydroxymethyl group is most consistent with the observed VCD pattern. VCD parameters were found significantly more sensitive to conformational changes than absorption or NMR. Concentration dependence of the absorption spectra indicated aggregation in concentrated solutions, but involved hydrogen bonds probably do not influence molecular conformation. PMID- 11777455 TI - A Suzuki coupling based route to 2,2'-bis(2-indenyl)biphenyl derivatives. AB - Because of the promising performance in olefin polymerization of 2,2'-bis(2 indenyldiyl)biphenyl zirconium dichloride, we developed a new and broadly applicable route to 2,2'-bis(2-indenyl)biphenyl derivatives. Reaction of the known 2,2'-diiodobiphenyl (26) with the new 2-indenyl boronic acid (23) did not result in the desired 2,2'-bis(2-indenyl)biphenyl (10); instead an isomer thereof, (spiro-1,1-(2,2'-biphenyl)-2-(2-indenyl)indane) (27), was obtained. It was found that compound 10 could be made via a palladium-catalyzed reaction of 2,2-biphenyldiboronic acid (31) with 2-bromoindene (21) under standard Suzuki reaction conditions. However, the yield of this reaction was low at low palladium catalyst loadings, due to a competitive hydrolysis reaction of 2,2 biphenyldiboronic acid (31). HTE techniques were used to find an economically viable protocol. Thus, use of the commercially available 1.0 molar solution of (n Bu)(4)NOH in methanol with cosolvent toluene led to precipitation of the pure product in a fast and clean reaction, using only 0.7 mol % (0.35 mol % per C-C) of the expensive palladium catalyst. PMID- 11777456 TI - Borderline between E1cB and E2 mechanisms. Chlorine isotope effects in base promoted elimination Reactions. AB - The chlorine leaving group isotope effect has been measured for the base-promoted elimination reaction of 1-(2-chloro-2-propyl)indene (1-Cl) in methanol at 30 degrees C: k(35)/k(37) = 1.0086 +/- 0.0007 with methoxide as the base and k(35)/k(37) = 1.0101 +/- 0.0001 with triethylamine (TEA) as the base. These very large chlorine isotope effects combined with large kinetic deuterium isotope effects of 7.1 and 8.4, respectively, are consistent not with the irreversible E1cB mechanism proposed previously (J. Am. Chem. Soc. 1977, 99, 7926) but with the E2 mechanism with transition states having large amounts of hydron transfer and very extensive cleavage of the bond to chlorine. PMID- 11777457 TI - The role of ion-molecule pairs in solvolysis reactions. Nucleophilic addition of water to a tertiary allylic carbocation. AB - The acid-catalyzed solvolysis of 2-methoxy-2-phenyl-3-butene (1-OMe) in 9.09 vol % acetonitrile in water provides 2-hydroxy-2-phenyl-3-butene (1-OH) as the predominant product under kinetic control along with the rearranged alcohol 1 hydroxy-3-phenyl-2-butene (2-OH) and a small amount of the rearranged ether 2 OMe. The more stable isomer 2-OH is the predominant product after long reaction time, K(eq) = [2-OH](eq)/[1-OH](eq) = 16. The ether 2-OMe reacts to give 2-OH and a trace of 1-OH. Solvolysis of 1-OMe in (18)O-labeled water/acetonitrile shows complete incorporation of (18)O in the product 1-OH, confirming that the reaction involves cleavage of the carbon-oxygen bond to the allylic carbon. A completely solvent-equilibrated allylic carbocation is not formed since the solvolysis of the corresponding chloride 1-chloro-3-phenyl-2-butene (2-Cl) yields a larger fraction of 1-OH. This may be attributed to a shielding effect from the chloride leaving group. Quantum chemical calculations of the geometry and charge distribution show that the cation should rather be described as a vinyl substituted benzyl cation than as an allyl cation, which is in accord with its higher reactivity at the tertiary carbon. PMID- 11777458 TI - Preparation of 8-substituted xanthine CVT-124 precursor by late stage pyrimidine ring closure. AB - To develop a novel route for the scaleable synthesis of the chiral xanthine CVT 124 (1, aka. BG9719), a method for the late stage pyrimidine ring closure of the nitrogen-protected endo 2-norbornenyl imidazole 3 was developed. The three component coupling of benzylamine, 2-cyanoglycine ethyl ester (4), and methyl 5 norbornene-2-carboximidate hydrochloride (5) was demonstrated to achieve 3 in 23 46% isolated yields. The imidazole 3 was then elaborated to construct the N benzyl xanthine 2 as a 1:1 mixture of exo and endo isomers, which were separable at this stage by chromatography. The nitrogen-protected endo xanthine 2 is a key intermediate in the synthesis of CVT-124. PMID- 11777459 TI - Efficient synthesis of phospholipids from glycidyl phosphates. AB - New efficient routes to enantiopure phospholipids, starting from (S)-glycidol, are described. Lysophosphatidic acids and phosphatidic acids were obtained in good overall yields from (S)-glycidol, in only three and four steps, respectively. Moreover, the strategy can also be used to produce phosphatidylcholines in three steps. Using dialkylphosphoramidites, (S)-glycidol was phosphorylated to give (R)-1-O-glycidyl dialkyl phosphates. Regiospecific epoxide opening, using hexadecanol or cesium palmitate, followed by phosphate deprotection, provided lysophosphatidic acids. 2-O-Esterification prior to phosphate deprotection provided 1,2-O-diacyl and 1-O-alkyl-2-O-acyl phosphatidic acids. Phosphorylation of (S)-glycidol using phosphorus oxychloride followed by in situ treatment with choline tosylate produced (R)-glycidyl phosphocholine. Subsequent nucleophilic opening of the epoxide using cesium palmitate produced 1 O-palmitoyl-sn-glycero-3-phosphocholine, which has been used in syntheses of phosphatidylcholines. PMID- 11777460 TI - Economical and environmentally friendly syntheses of 2-(phenylsulfonyl)-1,3 cyclohexadiene and 2-(phenylsulfonyl)-1,3-cycloheptadiene. AB - A large-scale and inexpensive synthesis of dienes 1 and 2 has been developed via a four-step procedure starting with benzenethiol and the corresponding cyclic ketone. No chromatography is required. PMID- 11777461 TI - Design and synthesis of push-pull chromophores for second-order nonlinear optics derived from rigidified thiophene-based pi-conjugating spacers. AB - Two series of push-pull chromophores built around thiophene-based pi-conjugating spacers rigidified either by covalent bonds or by noncovalent intramolecular interactions have been synthesized and characterized by UV-vis spectroscopy, electric field induced second harmonic generation (EFISH) and differential scanning calorimetry. Comparison of the linear and second-order nonlinear optical properties of chromophores based on a covalently bridged dithienylethylene (DTE) spacer with those of their analogues based on open chain DTE shows that the rigidification of the spacer produces a considerable bathochromic shift of the absorption maximum together with a dramatic enhancement of the molecular quadratic hyperpolarizability (mu beta) which reaches values among the highest reported so far. A second series of NLO-phores has been derived from a 2,2' bi(3,4-ethylenedioxythiophene) (BEDOT) pi-conjugating spacer. As indicated by X ray and UV-vis data, rigidification of the spacer originates in that case, from noncovalent intramolecular interactions between sulfur and oxygen atoms. Again, comparison with the parent compounds based on an unsubstituted bithiophene spacer reveals a marked red shift of the absorption maximum and a large enhancement of mu beta. In an attempt to distinguish the contribution of the electronic and geometrical effects of the ethylenedioxy group, a third series of NLO-phores based on 3,4-ethylenedioxythiophene (EDOT) and 3,4-dihexyloxythiophene spacers has been synthesized. Comparison with compounds based on unsubstituted thiophene shows that, despite a red shift of lambda(max), introduction of alkoxy groups leads to a decrease of mu beta. Theoretical calculations indicate that this effect results from a decrease of the dipole moment (mu) caused by the auxiliary electron-donor alkoxy groups on the thiophene ring. In contrast, replacement of BT by BEDOT produces an increase of mu, which associated with the noncovalent rigidification of the BT system accounts for the observed enhancement of mu beta. PMID- 11777462 TI - Successful Baylis-Hillman reaction of acrylamide with aromatic aldehydes. AB - Acrylamide and aromatic aldehydes were found to undergo the Baylis-Hillman reaction at ambient temperature in an aqueous medium in the presence of a stoichiometric amount of base catalyst, DABCO, to give the corresponding 3 hydroxy-2-methylenepropionamides in 61-99% yield. A faster competing, but reversible, non-Baylis-Hillman reaction was initially observed under the conditions to form N-acylhemiaminals, which later disappeared, as the desired Baylis-Hillman adduct was formed as the major product over an extended period of time (12-48 h). This represents the first demonstration of the Baylis-Hillman reaction of aldehydes with acrylamides, which were thought to be inert under atmospheric pressure and at ambient temperature. PMID- 11777463 TI - Syntheses of anolignans A and B using ruthenium-catalyzed cross-enyne metathesis. AB - Anolignans A and B were synthesized using ruthenium-catalyzed cross-enyne metathesis as the key steps. The 1,3-diene moieties of these natural products were constructed by the introduction of the methylene parts of ethylene into alkyne using Grubbs' catalyst. PMID- 11777465 TI - Lithiation of 2-heterosubstituted pyridines with BuLi-LiDMAE: evidence for regiospecificity at C-6. AB - The determination of the initial deprotonation site of 2-chloro- and 2 methoxypyridine during reaction with BuLi-LiDMAE has been investigated. A series of experiments on deuterated regioisomers revealed a direct lithiation at C-6 excluding a potential first classical ortholithiation and lithium equilibration in the reaction medium. These results suggested that the formation of lithium aggregates at the neighboring of the pyridinic nitrogen atom favored BuLi delivery at C-6 as well as 6-lithio intermediate stabilization. PMID- 11777464 TI - Synthesis and biological activities of conformationally restricted cyclopentenyl glutamate analogues. AB - An efficient method for preparing conformationally restricted cyclopentenyl glutamate analogues in a regioselective and diastereoselective manner has been developed using a formal [3 + 2] cycloaddition reaction of dehydroamino acids. Methods for preparing optically active versions of these compounds have also been devised. Of these compounds, (S)-2 is an agonist at the mGlu5 (EC(50) 18 microM) and mGlu2 (EC(50) 45 microM) receptors. PMID- 11777466 TI - First direct C-2-Lithiation of 4-DMAP. Convenient access to reactive functional derivatives and ligands. AB - The first direct alpha-lithiation of 4-DMAP has been performed via reaction with the BuLi-Me(2)N(CH(2))(2)OLi (BuLi-LiDMAE) reagent. This new methodology avoids the use of a activation-lithiation-regeneration sequence or halogen-metal exchange classically employed. New useful DMAP-containing synthons and polyheterocycles have been efficiently prepared. PMID- 11777467 TI - Regioselective organocadmium alkylations of substituted quinones. AB - A series of substituted quinones was alkylated with diethylcadmium. Regiochemistry of addition shifted from quinol formation to conjugate addition as a function of the steric and electronic effects of the substituents. PMID- 11777468 TI - Motuporamines, anti-invasion and anti-angiogenic alkaloids from the marine sponge Xestospongia exigua (Kirkpatrick): isolation, structure elucidation, analogue synthesis, and conformational analysis. AB - Extracts of the sponge Xestospongia exigua collected in Papua New Guinea were positive in a new assay for anti-invasion activity. Bioassay-guided fractionation led to the identification of the three known motuporamines A (1), B (2), and C (3) along with the new motuporamines D (4), E (5), and F (6) and a mixture of G, H, and I (15). Motuporamines A (1), B (2), and C (3) and the mixture of G, H, and I (15) were responsible for the anti-invasion activity of the crude extract. Motuporamine C (3) has also been found to be anti-angiogenic. A series of analogues of the motuporamines have been synthesized and evaluated for anti invasive activity. These SAR results revealed that a saturated 15-membered cyclic amine fused to the natural motuporamine diamine side chain (13) represented the optimal structure for anti-invasive activity in this family. Single-crystal X-ray diffraction analysis of one of the analogues 20 showed that in the solid state its 16-membered macrocyclic amine fragment adopted the [4444] quadrangular conformation predicted by calculations to be the lowest energy conformation for the corresponding cycloalkane, cyclohexadecane. These data along with literature X-ray data and conformational analysis for derivatives of azacyclotridecane have been used as precedents for predicting the lowest energy ring conformations of other motuporamines. The SAR data from the natural and synthetic motuporamines have been combined with the conformational analyses to provide an outline of the functionality and shape required for activity in this family of alkaloids and to design a new analogue 49 that showed good anti-invasion activity. PMID- 11777469 TI - Asymmetric Weitz-Scheffer epoxidation of isoflavones with hydroperoxides mediated by optically active phase-transfer catalysts. AB - The asymmetric Weitz-Scheffer epoxidation of the isoflavones 3, mediated by the cinchonine- and cinchonidine-derived phase-transfer catalysts (PTCs) 1, affords the enantiomerically enriched isoflavone epoxides 4 with ee values of up to 98% in nearly quantitative yields. With the appropriately configured PTC 1, both enantiomers of the isoflavone epoxides may be obtained by using the commercially available cumyl hydroperoxide 2b as oxidant. Methylation of the hydroxy functionality in the most effective PTC (1b) reduces significantly the enantioselectivity of the isoflavone epoxidation as illustrated for the substrate 3c. This fact indicates the pivotal role of the hydroxy group for enantioselective control, which is rationalized in terms of a hydrogen-bonded aggregate between the ether-oxygen atom of isoflavone 3 and the phase-transfer catalyst 1. The present attractive and convenient method should be useful for the preparation of optically active epoxides of the biologically relevant isoflavone structure. PMID- 11777471 TI - A theoretical study of the structures, energetics, stabilities, reactivities, and out-of-plane distortive tendencies of skeletally substituted benzenes (CH)(5)XH and (CH)(4)(XH)(2) (X = B(-), N(+), Al(-), Si, P(+), Ga(-), Ge, and As(+)). AB - Ab initio molecular orbital theory at Hartree-Fock (HF), post-Hartree-Fock (MP2 and CCSD(T)), and the hybrid density functional theory (B3LYP) calculations were done on the mono-(CH)(5)XH and diskeletally substituted (CH)(4)(XH)(2) benzenes (X = B(-), N(+), Al(-), Si, P(+), Ga(-), Ge, and As(+)). The computed relative energies of the disubstituted isomers show interesting trends. While the ortho isomer is the most stable for X = Ga(-), Ge, and As(+), meta was found to be the most stable for X = B(-), N(+), Al(-) and Si, and para was found to be the most stable for X = P(+). Various intricate factors that govern the relative stabilities, such as the sum of bond strengths in the twin Kekule forms, rule of topological charge stabilization (TCS), and electrostatic repulsion were critically examined. The sum of bond strengths in the twin Kekule forms was proved to be quite a successful measure in predicting the relative stability orders between ortho- and meta-/para-isomers. The rule of TCS breaks down especially in the presence of overwhelming factors such as the differences in the cumulative bond strengths of the two positional isomers; however, the stability ordering between the para- and meta-isomers is successfully predicted in most cases. The tendency for ring puckering increases a great deal especially when the substituents are from 3rd or 4th row. Extension of the popular inverse relationship between the thermodynamic stability and reactivity was found to be inapplicable for this class of compounds. The computed singlet-triplet energy differences and the chemical hardness (eta) values indicate that the skeletal substitution weakens the pi-strength of the benzenoid system and increases their reactivity. PMID- 11777470 TI - Overcrowding motifs in large PAHs. An ab initio study. AB - Planar and overcrowded LPAHs C(34)H(18) anthra[9,1,2-cde]benzo[rst]penaphene (1), benzo[rst]phenanthro[10,1,2-cde]pentaphene (2), tetrabenzo[a,cd,j,lm]perylene (3), tetrabenzo[a,cd,lm,o]perylene (4), and LPAHs C(38)H(18) anthra[2,1,9,8 klmno]naphtho[3,2,1,8,7-vwxyz]hexaphene (5), dianthra[2,1,9,8-stuva;2',1',9',8' hijkl]pentacene (6), dibenzo[jk,uv]dinaphtho[2,1,8,7-defg;2',1',8',7' opqr]perylene (7), diphenanthro[5,4,3-abcd;3',4',5'-lmno]perylene (8), potential products of peri-peri reductive couplings of benzanthrone and of naphthanthrone, respectively, were subjected to an ab initio study with emphasis on overcrowding motifs. The HF and DFT B3LYP methods were employed to calculate energies and geometries of the minima conformations of these LPAHs. The most stable LPAHs in these series were found to be planar C(2)(v)()-1 and C(2)(v)()-5, respectively. Among overcrowded LPAHs, twisted-folded C(2)-3 and C(2)-7 with two cove regions were found to be more stable than their respective isomers twisted-folded C(2)-4 and C(2)-8 with one fjord region each, in contrast to the semiempirical predictions. The energy differences between the most stable planar isomer and the overcrowded isomers were significantly smaller in the C(38)H(18) series, than in the C(34)H(18) series. Overcrowded twisted-folded C(2)-7 with two coves was found to be more stable than planar C(2)(h)()-6 by 2.0 kJ/mol (at B3LYP/6-311G), indicating enhanced role of aromatic stabilization and decreased destabilization due to overcrowding, with increasing the number of aromatic rings. Heats of formation of LPAHs 1-8 were derived from the ab initio total energies (at B3LYP/6 31G). A search of the conformational spaces of 3 and 4 revealed an anti-folded local minimum C(i)()-3 and a syn-folded transition state C(s)()-4, 23.7 and 120.3 kJ/mol higher in energy than the twisted-folded C(2)-3 and C(2)-4, respectively (at B3LYP/6-31G). The cove and fjord torsion angles in the C(38)H(18) series were found to be smaller than in the C(34)H(18) series. The nonbonding distances between carbon atoms at cove and fjord regions of the overcrowded LPAHs were found to be smaller than the sum of the van der Waals radii of two carbon atoms PMID- 11777472 TI - A convenient chemoenzymatic synthesis of (4aS,5S)-(+)-4,4a,5,6,7,8-hexahydro-5 hydroxy-4a-methylnaphthalen-2(3H)-one. AB - We have developed a convenient chemoenzymatic method for the preparation of (4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one by taking advantage of the excellent enantioselectivity of alcalase. Four different esters were compared, and the butanoate ester was found to be the best substrate. The stereochemistry of the product is the same as the one predicted from the binding model of alcalase. A simple extraction/partition procedure was used to separate the hydroxyenone product from the remaining ester. This practical procedure would be very useful in a gram-scale operation for securing the title compound in high optical purity. PMID- 11777473 TI - Revision of absolute configuration of enantiomeric (methylenecyclopropyl)carbinols obtained from (R)-(-)- and (S)-(+) epichlorohydrin and methylenetriphenylphosphorane. Implications for reaction mechanism and improved synthesis of antiviral methylenecyclopropane analogues of nucleosides. AB - Absolute configurations of enantiomeric methylenecyclopropanecarbinols obtained by reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+) tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-) (methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+) 6 and (+)-4 are then R,R and S, respectively. These assignments are in accord with an initial attack of phosphorane at the oxirane ring of epichlorohydrin. An improved preparation of key enantiomeric intermediates (R)-1a and (S)-1a, important for synthesis of antiviral purine methylenecyclopropane analogues of nucleosides, is also described. PMID- 11777474 TI - Diels-Alder cycloadditions of 3,5-dibromo-2-pyrone: a new ambident diene. AB - D-A cycloadditions of 3,5-dibromo-2-pyrone were investigated with a series of electronically and sterically distinct dienophiles. Our results showed that it is a highly potent ambident diene, being more reactive and stereoselective than monobromo-2-pyrones, and thus capable of generating a variety of bicycloadducts in much higher chemical yields and endo/exo ratios than monobromo-2-pyrones. Another interesting feature of this study is that the two bromine groups on the cycloadducts could be independently manipulated to produce other synthetically useful bicyclolactones. PMID- 11777475 TI - VO(acac)(2)-catalyzed oxidative coupling reactions of phosphonium salts. AB - A novel eco-safer protocol for the preparation of symmetric or asymmetric olefins directly from phosphonium salts under oxygen atmosphere in the presence of VO(acac)(2) (1.0 mol%) was developed. PMID- 11777476 TI - Regiochemistry in 1,3-dipolar cycloadditions of the azomethine ylide formed from diethyl aminomalonate and paraformaldehyde. AB - The azomethine ylide derived from the condensation of diethyl aminomalonate with paraformaldehyde undergoes 1,3-dipolar cycloadditions with acrylate and propiolate derivatives. Contrary to a previous report, these reactions yield mixtures of regioisomers generally favoring the 2,2,3-trisubstituted product. However, the relative quantity of the 2,2,4-trisubstituted product formed increases with an increase in the size of the activating group on the dipolaroplile. PMID- 11777477 TI - Proline-catalyzed one-step asymmetric synthesis of 5-hydroxy-(2E)-hexenal from acetaldehyde. AB - For the first time, the L-proline-catalyzed direct asymmetric self-aldolization of acetaldehyde is described affording (+)-(5S)-hydroxy-(2E)-hexenal 2 with ee's ranging from 57 to 90%. Further transformations of 2 into synthetically valuable building blocks are presented. A mechanism for the formation of 2 is proposed. PMID- 11777478 TI - Diamine synthesis: exploring the regioselectivity of ring opening of aziridinium ions. PMID- 11777479 TI - Barbier-type diastereoselective allylation of alpha-amino aldehydes with an enantiopure 2-sulfinylallyl building block. AB - An optimized procedure for the diastereoselective allylation under aqueous Barbier conditions of a series of alpha-amino aldehydes with our new chiral building block (S(s))-3-chloro-2-(p-tolylsulfinyl)-1-propene [(S(s))-1a] to afford enantiomerically pure sulfinylamino alcohols in good yields and diastereoselectivites is reported. High levels of diastereoinduction can be achieved from alpha-amino aldehydes configurationally related to natural alpha amino acids. PMID- 11777480 TI - Direct conversion of bromohydrins to ketones by a free radical elimination of hydrogen bromide. AB - Secondary beta-bromo alcohols can be transformed directly to ketones in very good yields by a free radical process. Tertiary beta-bromo alcohols do not react while the primary ones are transformed to aldehydes in lower yields. The reaction involves an abstraction of a hydrogen atom alpha to an OH group, followed by elimination of the bromine atom and subsequent tautomerization of an enol to a ketone. PMID- 11777481 TI - Highly enantioselective oxidation of cis-cyclopropylmethanols to corresponding aldehydes catalyzed by chloroperoxidase. AB - Chloroperoxidase (CPO) catalyzes the enantioselective oxidation of cyclopropylmethanols, such as 2-methylcyclopropylmethanol, to cyclopropyl aldehydes using tert-butyl hydroperoxide as the terminal oxidant. In all cases, CPO oxidation of cis-cyclopropanes shows much higher enantioselectivity than with the trans isomers, although CPO gives similar catalytic activity on both isomers. This presents the first example for a heme enzyme that catalyzes the enantioselective oxidation of cyclopropylmethanols. This finding enables a novel route to the synthesis of optically active cyclopropane derivatives, which occur widely in natural products and compounds of pharmaceutical interest. In addition, chiral cyclopropane molecules may be useful model substrates to investigate reaction mechanisms of CPO and the related cytochromes P450. PMID- 11777483 TI - Recent reviews. 63. PMID- 11777484 TI - Monitoring serum chorionic gonadotropin levels after mifepristone abortion. PMID- 11777485 TI - Quinacrine sterilization: a middle road. PMID- 11777486 TI - Quinacrine sterilization in Tripura, India. AB - A 611-case clinical trial of quinacrine sterilization (QS) was conducted at Agartala, Tripura State, India, using a unique protocol. No pregnancy failures were reported after a mean of 45.8 months of follow-up. Three trans-cervical insertions of 324 mg, 288 mg, and 252 mg quinacrine pellets were used in the first, second, and third insertions, respectively. Insertions were done on Days 6 10 of the menstrual cycle with the women remaining in a slight Trendelenberg position for 2 h post insertion. Antibiotics were prescribed after each insertion, and 3 months' supply of an additional contraception provided from first insertion. A unique inducement to report pregnancy failures was employed. Each woman was offered the equivalent of 5 months' family income to report any pregnancy following QS and a free menstrual regulation procedure. No pregnancies were reported. An independent follow-up visit to a systematic sample of 40 women found no pregnancies. PMID- 11777487 TI - Quinacrine non-surgical female sterilization in Bangladesh. AB - This study was undertaken to evaluate the efficacy, safety, and acceptability of transcervical applications of quinacrine along with other adjuvants, such as ampicillin and ibuprofen, for sterilization. The cohort consisted of 750 normal women who requested sterilization and volunteered for this method at the family planning clinic of a tertiary hospital and community clinics in Chittagong, Bangladesh. Several different protocols were followed from October 1989 to April 1999. Each woman received one or two insertions of 180 mg or 252 mg quinacrine with or without adjuvants including 55.5 mg ibuprofen or 125 mg ampicillin. Supplementary contraception was given in the form of combined oral contraceptive pills, barrier methods, or injection of depot medroxyprogesterone acetate for 3 months. Details of each protocol are described in the text. The gross pregnancy failure rate for insertion of 180 mg in 590 women was 3.9% compared to 1.9% for the 160 who received 252 mg. There were no serious complications, and side effects were transient. We conclude that quinacrine non-surgical sterilization is a safe, acceptably effective method when two insertions of 252 mg quinacrine with medroxyprogesterone injection as a supplement is used. PMID- 11777488 TI - Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants. AB - This open-label, randomized study evaluated the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE) following the application of a contraceptive patch (1/week) for three cycles (3 weeks/cycle). Healthy women (n = 24) wore a 20-cm(2) patch (ORTHO EVRA/EVRA) on either their abdomen or buttock during blood sampling weeks and on any of four approved sites at other times. Serum was analyzed for NGMN and EE from samples taken during Week 1 of Cycle 1 and Weeks 1-3 of Cycle 3. Steady-state conditions were achieved during the three cycle study. The patch delivered NGMN and EE at steady-state concentrations within their reference ranges throughout three cycles of treatment; reference ranges are based on studies with ORTHO-CYCLEN/Cilest. Steady-state serum concentrations and area under the curve from 0 to 168 h increased only slightly from Cycle 1, Week 1 to Cycle 3, Week 3 for NGMN and EE, indicating minimal accumulation. Treatment was well tolerated, and patch adhesion was excellent. PMID- 11777489 TI - The effects of two progestogen-only pills containing either desogestrel (75 microg/day) or levonorgestrel (30 microg/day) on lipid metabolism. AB - The effects of two progestogen-only pills (POPs) containing either desogestrel (75 microg/day) or levonorgestrel (30 microg/day) on lipid metabolism were compared in a double-blind, randomized study in Sweden and Finland. Eighty-one healthy female volunteers received either desogestrel 75 microg/day or levonorgestrel 30 microg/day for seven treatment periods of 28 days. The following lipid parameters were measured at screening and at treatment Periods 3 and 7: total cholesterol, total triglycerides, HDL-cholesterol, HDL(2) cholesterol, HDL(3)-cholesterol, LDL-cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, lipoprotein (a), and the carrier proteins sex hormone-binding globulin (SHBG) and cortisol-binding globulin. Overall, both study medications had similar, minimal effects on lipid metabolism. To summarize, compared with pre-treatment, no changes were observed for LDL-cholesterol and its protein fraction apolipoprotein B. The concentrations of total cholesterol and triglycerides decreased marginally. Decreasing trends were also seen for lipoprotein (a), HDL-cholesterol and its subfractions, HDL(2)-cholesterol and HDL(3)-cholesterol, and the apolipoproteins, apolipoprotein A-I and apolipoprotein A-II. The results indicated no significant differences between the groups in any of the parameters, with the exception of a smaller decrease in HDL(3)-cholesterol at treatment Period 7 for the desogestrel-containing POP compared with the levonorgestrel-containing POP and a significant difference between the two treatments for lipoprotein (a) at Period 3. The serum concentration of the carrier protein SHBG was found to be slightly higher in the desogestrel group, which may be a manifestation of the higher androgenicity of levonorgestrel compared with desogestrel. It can be concluded that the POP containing 75 microg desogestrel has a negligible effect on lipid metabolism. Despite the higher progestogen dose, the effect of this new POP is similar to that of a traditional POP containing 30 microg levonorgestrel. PMID- 11777490 TI - A 4-year follow-up study of women with Norplant-2 contraceptive implants. AB - One-hundred-thirty of 178 women who received Norplant-2 implants were followed prospectively for 4 years. Menstrual disorders were the most common reason for discontinuation. Only one patient conceived, for a failure rate of 0.6%. PMID- 11777491 TI - Efficacy and side effects of Norplant use in Thai women above the age of 35 years. AB - A prospective study of Norplant implant use in women aged above 35 years was conducted in Bangkok, Thailand. The purposes of this study were to evaluate the efficacy, menstrual patterns, and side effects of Norplant use in these women. A total of 100 women were recruited in a 1-year clinical study. Their mean age was 39.7 years. Most acceptors had completed secondary school. No accidental pregnancy occurred throughout the 1 year of use in this study. The most common menstrual pattern in these acceptors was amenorrhea followed by irregular bleeding. The major side effect was irregular bleeding. There was no significant change in systolic and diastolic blood pressure during the 1 year follow-up period. Thus, Norplant implant use in older women is a safe and effective contraceptive method. This should become another choice for contraception in women aged above 35 years who have contraindications for oral contraceptive use. PMID- 11777492 TI - Temporary discontinuation: a compliance issue in injectable users. AB - This study examined compliance in injectable users and followed women post discontinuation to document their contraceptive practices. A cohort of 189 predominantly new users of depot-medroxyprogesterone acetate and norethisterone oenanthate were recruited and followed for 2 years regardless of whether or not they continued the method. Continuation rates were 42% at 1 year and 21% at 2 years. Of the 78 women who discontinued the method, 31 reported that they were "taking a break." For 20 of these women, this break (nonuse segment) occurred within the 2-year period, and 15 of them returned to the injection before the end of study period. The other five switched methods after the nonuse segment. The mean length of the nonuse segment was 7 months (range 2-13 months). In all 20 women, no other contraceptive method was used, they remained sexually active, and started the break within 6 months of commencing use of the injectable. In addition, 11 women were in a self-reported nonuse segment at the end of the study and stated their intention to return to the method at a later date. Menstrual disturbances were cited as the main reason for the break. Strengthened counseling at method acceptance was identified as a strategy to decrease the frequency of breaks in injectable method use. PMID- 11777493 TI - Pilot study on the use of sublingual misoprostol for medical abortion. AB - A new route of sublingual administration of misoprostol was used by 25 women with first trimester, non-viable intrauterine gestation and by 18 women requesting mid trimester termination of pregnancy. Twenty-three women (92%, 95% CI 75, 98) with first trimester, non-viable gestation had complete abortion after sublingual misoprostol. All women (100%, 95% CI 82, 100) requesting second trimester abortion aborted, and the median induction-to-abortion interval was 11.6 h. Our preliminary results on sublingual misoprostol show that it is a promising method for medical abortion. Prospective randomized studies are required to compare its efficacy and side effects with vaginal misoprostol and to work out the dosage and dosing interval. PMID- 11777494 TI - Vaginal bleeding patterns among rural highland Bolivian women: relationship to fecundity and fetal loss. AB - Among the most common reasons given for discontinued use of some contraceptive methods is a disturbance in the menstrual cycle, particularly changes in vaginal bleeding. Work to date suggests marked populational variation in menses duration, but few data have been collected from South America. This longitudinal study of non-contracepting Aymara women (n = 189 providing 837 non-truncated bleeding episodes) identified conceptions and fetal loss via urine tests for human chorionic gonadotropin and classified episodes accordingly to test the hypotheses that (a) vaginal bleeding patterns differ between lactating and non-lactating women, (b) duration of vaginal bleeding accompanying fetal loss differs from that of menstruation, (c) menses preceding a conception are longer than those not followed by a conception. Compared to published values, mean menses duration (3.5 days) in these women was relatively short. Menses duration was not significantly correlated with current age, age at menarche or first birth, parity, time postpartum, or menstrual segment length. Mean menses duration (not preceding a conception) was comparable for lactating and non-lactating women. Mean duration of fetal loss bleeding did not differ from that of menses. Pre-conception episodes were significantly longer than those not followed by conception. Thus, because the rate of conceptions was twice as great among lactating than non lactating women, the mean duration of all menses (irrespective of conception) was significantly longer in lactating women. Bolivian, and perhaps other South American, women may be particularly disinclined to accept contraceptives (e.g., intrauterine devices) that modify an otherwise relatively brief menses duration. Therefore, a wide variety of contraceptive choices accompanied by population specific informed counseling is essential. In addition, these findings suggest that studies of fecundability limited to non-lactating women may be biased toward those of relatively lower fecundity and that menses duration may be predictive of risk for some cancers. PMID- 11777495 TI - Genetically engineered mice for studies of stress-related clinical conditions. AB - Genetically engineered mice with a specific deletion of targeted genes provide a novel and useful tool to study the endogenous mechanisms underlying aberrant behaviour. In this review we take the stress hormone (hypothalamic-pituitary adrenocortical) system as an example to demonstrate how refined molecular technologies have allowed to target individual genes involved in stress hormone regulation. We describe different gene targeting methods: the generation of "conventional" knock-out mice enables us to delete a gene of interest in every cell of the body. Equally important for the studies of gene function in the mouse is the use of tissue-specific regulatory systems that allow gene inactivation to be restricted to specific tissues and, in some cases, to specific time points during development, such as the "conditional" knock-out, or the application of antisense techniques. Importantly, deletion of individual genes is not providing animal models for certain psychiatric disorders as these are caused by a manifold of minor changes in a series of so-called susceptibility genes. However, these gene targeting methods have become valuable tools to dissect the functions of individual components of complex biological systems in behavioural neuroscience: genetically engineered animals help to unravel the complex interactions and correlations between individual genes, hormonal regulation and behaviour, the most complex form of biological organization. PMID- 11777496 TI - Adult separation anxiety: psychometric properties of a new structured clinical interview. AB - Separation anxiety has traditionally been characterized and assessed as a disorder that is unique to childhood. Yet the core symptoms of separation anxiety, i.e. excessive and often disabling distress when faced with actual or perceived separation from major attachment figures, may persist or even arise during adulthood. We report on the psychometric properties of a new structured clinical interview designed to assess symptoms of separation anxiety as experienced both during childhood and adulthood. This instrument, called the Structured Clinical Interview for Separation Anxiety Symptoms (or SCI-SAS), was administered as part of an assessment battery to 91 adult psychiatric outpatients and 20 non-psychiatric controls. Results indicate that this instrument displays excellent psychometric properties, including good internal consistency, a clear factor structure, and exceptional levels of convergent and discriminate validity. These results highlight the feasibility and potential clinical utility of assessing age-appropriate symptoms of separation anxiety experienced during adulthood. PMID- 11777497 TI - Validation of the behavioural activity rating scale (BARS): a novel measure of activity in agitated patients. AB - We report psychometric results of the Behavioural Activity Rating Scale (BARS) using data from three Phase III clinical trials of intramuscular ziprasidone in acutely agitated patients with psychosis (Studies 1 and 2) or in stable psychotic patients (Study 3). Convergent validity and divergent validity were assessed with baseline data from Studies 1 and 2 in subjects with acute agitation. To investigate convergent validity, we sought Pearson and Spearman correlation of BARS scores with scores on the Clinical Global Impression of Severity (CGI-S) Scale and a predefined cluster of agitation-related items from the Positive and Negative Syndrome Scale (PANSS). For divergent validity, we sought Pearson and Spearman correlation between BARS scores and a predefined cluster of PANSS items measuring negative symptoms. Discriminant validity was investigated with the help of subjects with moderate psychopathology (Study 3). Wilcoxon rank-sum and two sample t tests determined whether mean (or median) BARS scores differed between subjects with acute agitation (Studies 1 and 2) and moderate psychopathology (Study 3). Responsiveness to treatment effect and rater reliability were also evaluated. In Study 2, Pearson correlation coefficients of BARS scores with PANSS agitation items and CGI-S were moderate (convergent validity) and statistically significant (P<0.005). The correlation between BARS scores and PANSS negative component scores was low (divergent validity). Treatment effect size was larger for BARS than for PANSS agitation items and CGI-S (responsive to treatment differences). Virtually perfect inter- and intra-rater reliability was achieved. Study 1 produced similar results. BARS showed psychometrically valid properties for measurement of behavioral activity in acutely agitated patients with psychosis. PMID- 11777498 TI - A psychobiological approach to personality: examination within anxious outpatients. AB - OBJECTIVE: To examine Cloninger's psychobiological personality model among different anxiety and depressive outpatients as well as normal healthy comparisons. In addition, the relationship between the underlying temperament dimensions and behavioral coping strategies was also studied using the tri-axial model of coping. METHODS: Subjects were 120 outpatients presenting to an anxiety disorders specialty clinic and 17 normal comparisons. They underwent a semi structured clinical interview and completed a battery of questionnaires, including the Temperament and Character Inventory and the Strategic Approach to Coping Scale. RESULTS: On the temperament dimensions, the patients were elevated on the harm avoidance scale relative to the normal comparisons; the temperament substrate was not differentiated by the anxiety or affective diagnostic types nor was there differences between groups on the other temperament dimensions. Both severity of illness and the presence of a comorbid depressive disorder each contributed independently to harm avoidance scores. Hypotheses regarding the association between underlying temperament and behavioral coping strategies were supported for the dimensions of reward dependence and harm avoidance, but not for novelty seeking. CONCLUSIONS: Cloninger's psychobiological model is supported with the temperament of harm avoidance being the relevant dimension for anxiety and affective disorders. The underlying temperament structure also has clinical relevance for the type of coping strategies that are utilized by an individual. PMID- 11777499 TI - Panic disorder patients have reduced cyclic AMP in platelets. AB - Little is known about the intracellular mechanisms involved in the pathophysiology of panic disorder (PD). Abnormalities in the cyclic AMP system have been described in several psychiatric disorders but there are no studies in panic patients. We evaluated not only the levels of platelet cyclic AMP, but also cyclic GMP and nitric oxide synthase (NOS) activity in patients with PD at baseline and after treatment with clomipramine and in healthy volunteers. Platelet cyclic AMP was determined by enzymeimmunoassay, cyclic GMP by radioimmunoassay and NOS activity by the conversion of (3)H-arginine to (3)H citruline in 17 PD patients before treatment with clomipramine, after remission of panic attacks and in 22 healthy volunteers. Average baseline cyclic AMP of PD patients was lower than after remission of panic attacks (P<0.005) and lower than in healthy volunteers (P<0.005). Average cyclic AMP after remission of panic attacks was not significantly different than in healthy volunteers. There were no significant differences in cyclic GMP and NOS analysis. Our results suggest that PD patients without treatment have lower platelets cyclic AMP levels than healthy volunteers and that this decrease may be corrected by clomipramine. PMID- 11777502 TI - Response and survival in patients with progressive or recurrent serous ovarian tumors of low malignant potential. AB - OBJECTIVE: To evaluate the response to therapy and survival of patients with progressive or recurrent serous ovarian tumors of low malignant potential. METHODS: Fifty-three patients with progressive or recurrent serous ovarian tumors of low malignant potential were identified. Response was assessed and progression free and overall survival were analyzed. The influence of clinicopathologic factors on survival was determined. RESULTS: In 49 patients with known histology of progression or recurrence, 36 (73%) had low-grade serous carcinoma, and 13 (27%) had serous ovarian tumors of low malignant potential. Forty-five patients received nonsurgical therapy and had an evaluable response. There were six (13%) patients with a complete response and six (13%) patients with a partial response. The median time to first progression or recurrence was 5.6 years. Median survival from diagnosis of first recurrence was 7.7 years. Median survival from initial diagnosis was 21 years. Nineteen (36%) patients are dead of tumor. Patients who recurred with low-grade serous carcinoma were more likely to die of tumor than those with serous ovarian tumors of low malignant potential (47% versus 0%, P =.045). Optimal cytoreduction was associated with improved survival (P =.007). CONCLUSION: Patients with progressive or recurrent serous ovarian tumors of low malignant potential have a long interval from diagnosis to progression and from progression to death, resulting in extended overall survival. Recurrence as low grade serous carcinoma and failure to achieve optimal secondary cytoreduction were adverse prognostic factors. There were few responses to nonsurgical therapy. PMID- 11777503 TI - Epithelial ovarian tumors of low malignant potential: the role of microinvasion. AB - OBJECTIVE: To identify prognostic factors that may be used to predict an aggressive disease course and poor outcome in patients with epithelial ovarian tumors of low malignant potential (borderline tumors). METHODS: Data on 126 patients with ovarian borderline tumors were analyzed with regard to demographic characteristics, staging, presence of microinvasion, duration of follow-up, recurrence rate, rate of recurrence as invasive disease, mortality rate, preoperative and postoperative CA-125, and treatment. Chi-square and Fisher exact tests were used to evaluate proportions for statistical significance. Disease free and overall survival was calculated by using the Kaplan-Meier method and log rank test. RESULTS: Patients were followed for a median of 39.0 months (mean 47.8 months). Seven patients (5.6%) had recurrent disease. Advanced stage disease and microinvasion were associated with significantly higher recurrence and mortality rates than were stage I/II disease and borderline tumors without microinvasion, respectively. Two of 13 (15%, 95% CI 8.7, 21.3) patients with microinvasion died of recurrent invasive cancer, whereas only 1 out of 113 patients without microinvasion died of recurrent borderline tumor (OR 20.4, 95% CI 1.2, 239). All 3 patients with an aggressive disease course and poor outcome had increasing CA 125 levels at the time of recurrence. CONCLUSION: Certain patients with microinvasion may be at higher risk for recurrence as invasive disease and may require different treatment strategies. CA 125 monitoring may have a role in early detection of recurrence in patients with aggressive disease. PMID- 11777504 TI - Assessment of vulvovaginal complaints: accuracy of telephone triage and in-office diagnosis. AB - OBJECTIVE: To examine the agreement between telephone and office management of vulvovaginal complaints and to assess the accuracy of diagnosis of vulvovaginitis. METHODS: Prospective structured telephone nurse interviews of all patients with vulvovaginal complaints who called the Kaiser Permanente Telephone Call Center were conducted. Patients were appointed to a physician, nurse midwife, or physician's assistant for office evaluation. Both groups (nurses and practitioners) made independent diagnosis and treatment decisions. kappa coefficients were used to evaluate the interexaminer agreement between telephone nurses and practitioners, and practitioners and traditional diagnostic tests. RESULTS: A total of 485 patients underwent telephone interviews, and 253 (52%) completed the study protocol. kappa values showed poor agreement between nurses and practitioners for bacterial vaginosis (0.12), candidiasis (0.22), and trichomoniasis (-0.05). Practitioners failed to accurately diagnose vaginitis when kappa values were analyzed. There was also poor agreement between telephone nurses and practitioners regarding the necessity of an office visit (0.14). CONCLUSION: This prospective study challenges the notion that the telephone is an effective tool to diagnose and treat vulvovaginal complaints. Moreover, given the poor agreement between practitioners' diagnoses and microbiologic and microscopic data, further study into optimal diagnosis of vulvovaginitis is needed. PMID- 11777505 TI - Is pelvic organ prolapse a cause of pelvic or low back pain? AB - OBJECTIVE: To test the null hypothesis that there is no association between pelvic organ prolapse and pelvic or low back pain. METHODS: A total of 152 consecutive patients with pelvic organ prolapse completed a visual faces scale to quantify the amount of pelvic or low back pain present. Pelvic organ prolapse severity was graded by three techniques: 1) pelvic organ prolapse quantification staging; 2) descent of the leading edge of prolapse; and 3) dynamic cystoproctography. Linear and nonlinear associations of pelvic organ prolapse quantification staging, descent of the leading edge of prolapse, and dynamic cystoproctography findings with pelvic or low back pain were assessed. We also characterized the nature of any significant nonlinear associations. RESULTS: Descent of the leading edge of prolapse was linearly associated with low back pain. Patients with greater descent of the leading edge of their prolapse reported less low back pain (r = -0.176, P =.034). Bladder descent during dynamic cystoproctography was nonlinearly associated with low back pain (P =.037). Neither of these associations was statistically significant after controlling for patient age and prior prolapse surgery. There were no linear or nonlinear associations between pelvic organ prolapse and pelvic pain. CONCLUSION: Based on the data, pelvic organ prolapse is not a cause of pelvic or low back pain. PMID- 11777506 TI - Active pushing versus passive fetal descent in the second stage of labor: a randomized controlled trial. AB - OBJECTIVE: To compare perinatal outcomes among women with epidural anesthesia who were encouraged to push at complete dilatation with those who had a period of rest before pushing began. METHODS: After a power analysis to determine appropriate sample size (based upon an alpha error rate of.05% and 80% power), a prospective randomized trial of 252 women with epidural anesthesia was conducted. Patients were randomized to a rest period or immediate pushing at complete dilatation. Variables measured included rate of fetal descent, length of time of pushing, the number and type of fetal heart rate decelerations, Apgar scores, arterial cord pH values, perineal injuries, type of delivery, length of second stage, maternal fatigue, and endometritis. RESULTS: When a period of rest was used before pushing, we found a longer second stage, decreased pushing time, fewer decelerations, and, in primiparous women, less fatigue compared with control patients. Apgar scores, arterial cord pH values, rates of perineal injury, instrument delivery, and endometritis were similar in both groups. CONCLUSION: Delayed pushing was not associated with demonstrable adverse outcome, despite second-stage length of up to 4.9 hours. In select patients, such delay may be of benefit. PMID- 11777507 TI - Risk of warfarin during pregnancy with mechanical valve prostheses. AB - OBJECTIVE: To assess the determinants of pregnancy outcome in patients with mechanical valve prostheses anticoagulated with warfarin. METHODS: Between January 1987 and January 2000, 52 patients with mechanical valve prostheses who had 71 pregnancies were anticoagulated with warfarin for the entire duration of pregnancy. Warfarin was withdrawn 48 hours before and 24 hours after a scheduled cesarean delivery carried out by the end of the 37th gestational week. The targeted international normalized ratio ranged between 2.25 and 4.0, depending on the prosthetic model. Exact univariate and multivariable analyses were performed to assess which among the following variables predicted poor pregnancy outcome: patient age, prosthetic model, site of implantation, average international normalized ratio, and average daily dose of warfarin. RESULTS: Pregnancy loss occurred in 23 of 71 of pregnancies, stillbirth in five of 71, embryopathy in four of 71 (two aborted fetuses and two full-term infants). There were no maternal deaths or thromboembolic or hemorrhagic complications. Warfarin daily dosage over 5 mg per day was a significant predictor of poor pregnancy outcome (P <.001). CONCLUSION: The risk for pregnancy complications in patients treated with sodium warfarin is higher when the mean daily dose exceeds 5 mg. PMID- 11777508 TI - Interdelivery interval and the success of vaginal birth after cesarean delivery. AB - OBJECTIVE: To determine whether a short interdelivery interval is associated with decreased rate of successful vaginal birth after cesarean (VBAC). METHODS: A retrospective cohort study from January 1, 1997, to December 31, 2000, was conducted. Patients with previous cesarean delivery who attempted VBAC were identified. The analysis was limited to patients at term with one prior cesarean. The interdelivery interval was calculated in months between the index pregnancy and prior cesarean delivery. RESULTS: A total of 1516 subjects who attempted VBAC were identified among 24,162 deliveries, with complete data available in 1185 cases. The VBAC success rate was 79.0% for patients with an interdelivery interval less than 19 months compared with 85.5% for patients with an interval delivery greater than or equal to 19 months (P =.12). For patients whose labors were induced, interdelivery intervals of less than 19 months were associated with a decreased rate of VBAC success when compared with longer intervals (P <.01). Sufficient power (beta =.95) existed to detect a 64% difference between the groups (alpha =.05). No significant difference was detected in women who underwent spontaneous labor (P =.98). There was no difference in the rate of symptomatic uterine rupture (P = 1.00). CONCLUSION: Interdelivery intervals of less than 19 months were associated with a decreased rate of VBAC success in patients who underwent induction, a difference not found in those with spontaneous labor. PMID- 11777509 TI - Preconception counseling improves folate status of women planning pregnancy. AB - OBJECTIVE: To assess whether counseling women planning pregnancy to start or continue folic acid supplementation improves folate status. METHODS: Women and their partners reported folic acid supplement intake in a preconceptional health questionnaire, and the women were categorized as reported "users" or "nonusers" of supplements before counseling. The use of periconceptional folic acid was addressed at a subsequent preconceptional consultation. Differences between reported supplement users and nonusers before counseling as well as between assumed users and nonusers of folic acid (with precounseling red cell and serum folate levels above and below 590 nmol/L and 20 nmol/L, respectively) were analyzed. RESULTS: A total of 111 (66%) of 168 eligible women participated. Estimated mean red cell folate levels of women who reported no use of folic acid supplements before counseling increased significantly after 4 months from 540 nmol/L to 680 nmol/L. Red cell folate levels of women who reported taking supplements (44%) remained stable up to 1 year after counseling. Women with low precounseling folate levels showed a highly significant mean increase in red cell folate from 475 nmol/L to 689 nmol/L 4 months after counseling. CONCLUSION: Addressing periconceptional folic acid use at a preconceptional consultation improves folate status among women planning to conceive. PMID- 11777510 TI - Postoperative fatigue negatively impacts the daily lives of patients recovering from hysterectomy. AB - OBJECTIVE: To assess, from the patient's perspective, the prevalence and impact of postoperative fatigue after hysterectomy and to increase understanding of physician-patient communications before and after surgery regarding recovery and diminished postoperative energy level. METHODS: We completed a telephone survey of 300 women aged 25-50 who had undergone a hysterectomy or myomectomy within the past 2 years. The patients were recruited randomly from two national, random samples of households: 1) women aged 25-50, and 2) women taking hormone replacement therapy in the target age range. Patients were asked a series of questions about their postoperative fatigue after surgery. RESULTS: Overall, 74% of patients experienced moderate-to-severe fatigue within the first few weeks after surgery. Fatigue occurred more frequently and persisted twice as long as pain, the next most frequent symptom, which was experienced by 63% of patients overall. Fatigue was the symptom that most interfered with daily activities (37%) and also contributed to feelings of frustration (52%), to depression (37%), and to difficulty in concentrating (42%). Patients employed at the time of surgery missed an average of 5.8 weeks of work; 69% of those surveyed required 2 or more weeks of caregiver assistance. Postoperative fatigue was discussed by 68% of patients' physicians before surgery, and 57% of patients discussed postoperative fatigue with their physicians after surgery. Oral iron therapy and dietary supplements were the most frequently recommended treatments; 52% of patients were not offered any treatments or recommendations to alleviate their fatigue. CONCLUSIONS: Fatigue is a highly prevalent posthysterectomy and myomectomy symptom and has substantial negative physical, psychosocial, and economic effects on patients during recovery. PMID- 11777511 TI - Dexamethasone for the prevention of nausea and vomiting after dilatation and curettage: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy and safety of dexamethasone administered intravenously at three different doses (4 mg, 8 mg, 16 mg) for the prevention of nausea and vomiting after dilatation and curettage. METHODS: In a prospective, randomized, double-masked, placebo-controlled trial, 120 women received placebo or dexamethasone intravenously at doses of 4 mg, 8 mg, or 16 mg immediately before induction of anesthesia (n = 30 in each group). Propofol-based general anesthetic was used. Emetic episodes and safety assessments were performed. To estimate a sufficient sample size, it was calculated that 30 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients who were emesis-free (no nausea, retching, or vomiting) 0-24 hours after anesthesia was 57% with dexamethasone 4 mg (P =.796), 87% with dexamethasone 8 mg (P =.005), and 87% with dexamethasone 16 mg (P =.005), compared with placebo (50%). Patients who had received dexamethasone 8 mg or 16 mg were more satisfied than those who had received placebo (P <.05). No clinically important adverse events were observed in any of the groups. CONCLUSION: Dexamethasone 8 mg is an effective antiemetic for preventing postoperative nausea and vomiting 0-24 hours after anesthesia in women undergoing propofol-based general anesthesia for termination of pregnancy. Increasing the dose to 16 mg provided no additional benefit. PMID- 11777512 TI - Urethral sphincter morphology in women with detrusor instability. AB - OBJECTIVE: To determine whether sonographic urethral sphincter morphology is different in patients with detrusor instability than in those with normal urodynamic testing. METHODS: Patients from a population of women presenting for evaluation of urinary incontinence or pelvic organ prolapse underwent intraurethral ultrasonography before multichannel urodynamic testing. Maximal rhabdosphincter thickness, total urethral diameter, total urethral circumference, and longitudinal smooth muscle thickness, diameter, and circumference were measured. For patients with detrusor instability, the strength of the involuntary detrusor contraction and the bladder volume at its onset were recorded. These data were compared with information from history questionnaires and urodynamic evaluations. RESULTS: The 17 patients with detrusor instability and 16 patients with normal urodynamic testing did not differ with respect to age, vaginal parity, race, weight, body mass index, prior continence surgery, or maximal total urethral closure pressure. Patients with detrusor instability, had decreased urethral longitudinal smooth muscle thickness (3.0 +/- 0.9 mm vs 4.1 +/- 0.7 mm, P =.001), total urethral diameter (18.0 +/- 1.6 mm vs 19.4 +/- 1.4 mm, P =.01), and total urethral circumference (5.65 +/- 0.5 cm vs 6.1 +/- 0.4 cm, P =.012) compared with those with normal urodynamic tests. A linear relationship between rhabdosphincter thickness and strength of involuntary detrusor contraction was observed (r =.686, P =.002). CONCLUSION: Urethral sphincter morphology is different in patients with detrusor instability compared with those who have normal urodynamic tests. These findings provide an anatomic basis for the physiologic findings in patients with "urethrogenic" detrusor instability. PMID- 11777513 TI - Computer-assisted virtual urethral pressure profile in the assessment of female genuine stress incontinence. AB - OBJECTIVE: To compare computer-assisted virtual urethral pressure profile changes between women with and without genuine stress incontinence. METHODS: A full urogynecologic assessment including conventional urodynamic measurements and a clinical stress test were carried out. Computer-assisted virtual urethral pressure profile uses conventional urethral pressure profile measurements during stress, with the only change being that withdrawal of the catheter is stopped at distinct points along the whole urethra while the patient coughs. Cough-related changes of maximal urethral closure pressure, functional urethral length, and area under the urethral closure pressure curve were determined. RESULTS: Sixty one women were enrolled in our study: 30 symptom-free women (group A) were continent, and genuine stress incontinence was present in 31 patients (group B) complaining of urinary loss. Significant differences between group A and group B women were found for all parameters of computer-assisted virtual urethral pressure profile including maximal urethral closure pressure (91.59 +/- 39.00 versus 20.70 +/- 22.61 cm H(2)O; P <.001), functional urethral length (31.81 +/- 9.02 versus 10.83 +/- 10.76 mm; P <.001), and the area under the urethral closure pressure curve (2036 +/- 1025.29 versus 253 +/- 206.69 cm H(2)O x mm; P <.001). CONCLUSION: Computer-assisted virtual urethral pressure profile is a new application of urethral pressure profile measurements during stress. Our data show significant differences between continent women and patients with genuine stress incontinence. Further studies are needed to assess the potential of computer-assisted virtual urethral pressure profile for diagnosing genuine stress incontinence. PMID- 11777514 TI - Dose-range effects of propofol for reducing emetic symptoms during cesarean delivery. AB - OBJECTIVE: To evaluate the efficacy and safety of propofol at subhypnotic doses for reducing emetic symptoms in parturients undergoing cesarean delivery under spinal anesthesia. METHODS: In a randomized, double-masked trial, 80 patients received lidocaine intravenously 0.1 mg/kg (for injection pain relief) followed by either placebo or propofol at three different doses (0.5 mg/kg per hour, 1.0 mg/kg per hour, 2.0 mg/kg per hour) (n = 20 in each group) immediately after clamping of the umbilical cord. Emetic episodes and safety assessments were performed during spinal anesthesia for cesarean delivery. To estimate a sufficient sample size, it was calculated that 20 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients experiencing no emetic symptoms in an intraoperative, postdelivery period was 45% with propofol 0.5 mg/kg per hour (P =.5), 80% with propofol 1.0 mg/kg per hour (P =.011), and 80% with propofol 2.0 mg/kg per hour (P =.011), compared with placebo (40%). No clinically serious adverse events caused by the study drugs were observed. CONCLUSION: Propofol 1.0 mg/kg per hour is the minimum effective subhypnotic dose for reducing emetic symptoms during cesarean delivery. Increasing the dose to 2.0 mg/kg per hour provides no further benefit. PMID- 11777515 TI - Amniotic fluid matrix metalloproteinase-9 and interleukin-6 in predicting intra amniotic infection. AB - OBJECTIVE: To assess the potential role of amniotic fluid (AF) matrix metalloproteinase-9 and interleukin-6 in predicting intra-amniotic infection. METHODS: Eighty-four women with singleton gestations with preterm contraction, preterm labor, preterm premature rupture of membranes, or clinical suspicion of intra-amniotic infection were studied. Amniotic fluid was obtained by transabdominal amniocentesis before starting any treatment. Intra-amniotic infection was defined as the presence of a positive AF culture. Amniotic fluid glucose concentration, leukocytes, matrix metalloproteinase-9, and interleukin-6 were determined. RESULTS: Amniotic fluid matrix metalloproteinase-9 and interleukin-6 levels were significantly higher in women with intra-amniotic infection than in those without. With intra-amniotic infection, levels of matrix metalloproteinase-9 significantly correlated with interleukin-6 (r = 0.813, P <.001). Each of matrix metalloproteinase-9 and interleukin-6 significantly correlated with AF leukocytes and inversely correlated with AF glucose. Using AF cutoff levels of 13.6 ng/mL for matrix metalloproteinase-9 and 11.4 ng/mL for interleukin-6, the sensitivity, specificity, and positive and negative predictive values for diagnosing intra-amniotic infection were 77% versus 73%, 100% versus 79%, 100% versus 61%, and 90% versus 86%, respectively. Combining AF matrix metalloproteinase-9 with interleukin-6 slightly improved the sensitivity and the negative predictive values in diagnosing intra-amniotic infection. CONCLUSIONS: Amniotic fluid matrix metalloproteinase-9 and interleukin-6 are significantly elevated in women with intra-amniotic infection. Amniotic fluid matrix metalloproteinase-9 is an accurate biochemical marker in predicting intra amniotic infection with better sensitivity, specificity, and positive and negative predictive values than interleukin-6. PMID- 11777516 TI - Relationship of insulin-like growth factor-I and insulin-like growth factor binding proteins in umbilical cord plasma to preeclampsia and infant birth weight. AB - OBJECTIVE: To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS: Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS: Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP 1 was more than twice as high as in controls (both P <.01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION: Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease. PMID- 11777517 TI - Impact of fetal reduction on the incidence of gestational diabetes. AB - OBJECTIVE: To estimate the rate of gestational diabetes in triplet pregnancies and to assess the impact of fetal reduction on the incidence of this complication. METHODS: One hundred eighty-eight consecutive triplet pregnancies referred to the Sheba Medical Center between 1994 and 1998 were included. One hundred three of these pregnancies continued as triplets, whereas 85 women elected to undergo fetal reduction to twins. The incidence of gestational diabetes (based on the criteria of Carpenter and Coustan) and other outcome variables were compared between the two groups. Student t-tests and chi(2) analysis were used as appropriate. RESULTS: Mean (+/-SD) maternal age was 29.2 +/ 4.8 in the triplet group and 29.3 +/- 4.1 in the reduction group. The groups had similar median parity (1.6 +/- 1.1 in the triplet group and 1.5 +/- 0.7 in the reduction group). The rate of gestational diabetes was significantly higher in the triplet group than in the reduction group (22.3% vs 5.8%). A lower birth weight (1764 +/- 448 g vs 2208 +/- 526 g) and an earlier gestational age at delivery (33.4 +/- 2.8 weeks vs 36.0 +/- 2.8 weeks) were observed in the triplet group compared with the reduction group. CONCLUSION: The number of fetuses in multifetal pregnancies influences the incidence of gestational diabetes. These findings support the hypothesis that an increase in placental mass and, thus, an increase in diabetogenic hormones play a role in the etiology of gestational diabetes. PMID- 11777518 TI - Effect of a resident-created study guide on examination scores. AB - OBJECTIVE: To evaluate the effect of a resident-created study guide on Council on Resident Education in Obstetrics and Gynecology (CREOG) In-Training and American Board of Obstetrics and Gynecology (ABOG) written examination scores. METHODS: In 1995, a group of residents at the University of Texas Southwestern Medical Center began creating an annual study guide based on the CREOG Test Item Summary Booklet. Individual, program, and national scores for 3 years before the intervention were compared with scores for 3 years after the intervention. A four way analysis of variance was used to evaluate the effect of the intervention accounting for sex, Alpha Omega Alpha Medical Honor Society (AOA) status, and calendar year. A random effects model was also used to adjust for confounders. Categoric variables were compared using Mantel-Haenszel chi(2). Program failure rates for the ABOG written examination before and after the intervention were compared with relative risks. RESULTS: After introduction of the study guide, the annual difference between our program and the national percent correct increased significantly (2.1% versus 4.8%, P <.001), after adjustment for AOA status and calendar year. The improvement was distributed among resident levels 2-4 (all P <.02) and for non-AOA residents (P < or = .001). The relative risk of failure of the written ABOG examination before the study guide was 3.5 (95% confidence interval 0.77, 15.9). CONCLUSION: These findings demonstrate an important cooperative use of the Test Item Summary Booklet as an educational resource. PMID- 11777519 TI - Does antenatal corticosteroid therapy affect birth weight and head circumference? AB - OBJECTIVE: To determine whether antenatal corticosteroid use is associated with weight and head circumference at birth. METHODS: We conducted a retrospective analysis of nonanomalous newborns admitted to 100 neonatal intensive care units from 23 to 34 6/7 weeks of gestation using multivariable analysis of variance that controlled for several potentially confounding variables. RESULTS: There were 14,338 cases of birth weight and 13,670 for head circumference available for analysis. Independent variables included maternal age, race, nulliparity, poor prenatal care, multiple gestation, obstetric complications, alcohol, smoking, illicit drugs, presentation, gestational age at birth, and method of delivery. The mean (+/-SD) birth weight was 1671 +/- 574 g and head circumference was 289 +/- 33 mm. The multivariable effect of antenatal corticosteroid on birth weight (mean +/- SE) was -63 +/- 5.7 g and on head circumference was -3.1 +/- 0.4 mm. Even after controlling for birth weight, a significant reduction in head circumference (-1.2 +/- 0.3 mm; 95% CI = -1.8, -0.6) was associated with antenatal corticosteroid use. This suggested that antenatal corticosteroids were associated with a greater reduction in brain growth than somatic growth. CONCLUSION: Antenatal corticosteroid may be associated with a reduction in birth weight and head circumference, independent of other major predictive factors. The reduction in head circumference persists even after controlling for the reduction in birth weight. The clinical significance of these findings is unknown. PMID- 11777520 TI - Effect of antenatal and postnatal corticosteroid therapy on weight gain and head circumference growth in the nursery. AB - OBJECTIVE: To assess the effect of antenatal and postnatal corticosteroids on head circumference growth and weight gain from birth to discharge. METHODS: We conducted a retrospective analysis of nonanomalous newborns admitted to the neonatal intensive care unit from 23 to 34 6/7 weeks of gestation. Independent variables included maternal age, race, nulliparity, poor prenatal care, multiple gestation, obstetric complications, alcohol, tocolytic drugs, smoking, illicit drugs, gestational age at birth, presentation, method of delivery, 5-minute Apgar score < 7, surfactant use, severe intracranial hemorrhage, and length of stay. RESULTS: Antenatal and postnatal corticosteroids were given in 62% and 14% of the newborns, respectively, and 10% of newborns received both. The mean (+/-SD) weight gain and head circumference growth in the nursery was 440 +/- 582 g (n = 14,217) and 2.54 +/- 3.42 cm (n = 12,808), respectively. After multivariable analysis, use of antenatal corticosteroids did not affect weight gain (3.6 +/- 4.6 g) and head circumference growth (0.05 +/- 0.04 cm) compared with no exposure to perinatal corticosteroids, but postnatal corticosteroids were associated with significant reductions in weight gain and head circumference growth (-120 +/- 12.2 g and -0.53 +/- 0.11 cm, respectively). CONCLUSIONS: Antenatal corticosteroid therapy did not affect weight gain or head circumference growth in the nursery, even when used in conjunction with postnatal corticosteroid therapy. PMID- 11777521 TI - The medical and economic impact of the Newborns' and Mothers' Health Protection Act. AB - OBJECTIVE: We evaluated the effect of the Newborns' and Mothers' Health Protection Act on clinical and cost outcomes. METHODS: We conducted an observational study of 18,023 healthy, mother-infant dyads before (n = 8670) and after (n = 9353) implementation of the Newborns' and Mothers' Health Protection Act legislation. Logistic regression was used to calculate adjusted odds ratios (ORs) for the following outcome measures: length of stay at least 48 hours, satisfaction with maternal length of stay, 7- and 30-day hospital readmission utilization, and 7- and 30-day emergency room utilization. Analysis of covariance was used to evaluate adjusted mean hospitalization costs per delivery. RESULTS: Mothers in the postlegislation period were more likely to have hospital stays at least 48 hours (OR 3.99; 95% confidence interval [CI] 3.57, 4.44) and rate their length of stay as "about right" (OR 5.54; 95% CI 4.76, 6.46) compared with mothers in the prelegislation period. Neonates in the postlegislation period were more likely to have hospital stays of at least 48 hours (OR 3.96; 95% CI 3.54, 4.43) and less likely to be rehospitalized within 7 days after hospitalization (OR 0.61; 95% CI 0.40, 0.95) compared with neonates in the prelegislation period. Adjusted mean hospitalization costs increased $116 per delivery in the postlegislation period. CONCLUSIONS: After implementation of the Newborns' and Mothers' Health Protection Act legislation, maternal and newborn length of stay and maternal satisfaction with length of stay increased substantially, and hospitalization costs increased significantly. The strongest clinical benefit was observed among neonates who were at a lower risk for hospitalization within 1 week of discharge. With the exception of 30-day emergency room utilization, there was insufficient statistical power to test for differences among other maternal clinical outcomes. PMID- 11777522 TI - New concerns about thalidomide. AB - Recently, the Food and Drug Administration (FDA) approved thalidomide for the treatment of the painful symptoms of erythema nodosum leprosum. This most recent FDA decision is a marked reversal to its previous rejection of this drug in the 1960s. The initial rejection by the FDA in the 1960s spared countless American children as thalidomide was shown to cause birth defects and miscarriages worldwide. The FDA's reputation as one of the finest consumer safety authorities was strengthened because of this decision. The recent approval of thalidomide by the FDA, with accompanying strict guidelines and monitoring procedures, has not only brought forth potential benefits, but also created new potential problems. PMID- 11777523 TI - Intrapartum fetal stimulation tests: a meta-analysis. AB - OBJECTIVE: To assess the performance of stimulation tests for the prediction of intrapartum fetal acidemia. DATA SOURCES: We conducted a MEDLINE (Internet Grateful Med) literature review from 1966 to 2000 using the terms "fetal scalp pH," "fetal scalp stimulation," and "fetal acoustic stimulation." STUDY SELECTION: Articles were included if sensitivity, specificity, and predictive values for intrapartum fetal acidemia could be calculated. Reactivity was a fetal heart rate (FHR) acceleration of 15 beats per minute for 15 seconds. Likelihood ratio and 95% confidence intervals (CIs) for four different fetal provocations were calculated using the Cochrane collaboration 2000 Review Manager 4.1. This permitted an estimate of the degree of confidence surrounding the point estimate of the likelihood ratio for the presence or absence of acidemia given a positive or negative test. The likelihood ratio is a stable predictive property of any test because it combines information from both sensitivity and specificity, is independent of prevalence, and avoids the limitations of traditional predictive values. TABULATION, INTEGRATION, AND RESULTS: Eleven of 512 articles met criteria for inclusion and included four stimulation tests - fetal scalp puncture, Allis clamp scalp stimulation, vibroacoustic stimulation, and digital scalp stimulation. Pooled likelihood ratio and 95% CIs were similar among the four different stimulation tests. Each test was very useful at predicting both the lack of and the presence of fetal acidemia. Likelihood ratio and 95% CIs for the prediction of fetal acidemia given a positive test were: scalp puncture 8.54 (CI 1.28, 56.96), Allis clamp 10.4 (CI 1.47, 73.61), vibroacoustic stimulation 5.06 (CI 2.69, 9.50), and digital 15.68 (CI 3.22, 76.24). For a negative test, these were: scalp puncture 0.12 (CI 0.02, 0.78), Allis clamp 0.10 (CI 0.01, 0.68), vibroacoustic stimulation 0.20 (CI 0.11, 0.37), and digital 0.06 (CI 0.01, 0.31). CONCLUSION: Intrapartum stimulation tests appear to be useful to rule out fetal acidemia in the setting of a nonreassuring FHR pattern. Our data reveal the degree of confidence around the estimate of the likelihood ratio of a stimulation test. The very low negative likelihood ratios warrant the use of these tests when a nonreassuring intrapartum FHR pattern appears. Because these tests are less than perfect, caution is advised; careful continued monitoring with repeat testing during the course of labor should be performed as long as suspicious FHR patterns persist. Fetal scalp pH should be determined whenever possible after a positive stimulation test (lack of acceleration). PMID- 11777524 TI - Recurrent pregnancy loss with antiphospholipid antibody: a systematic review of therapeutic trials. AB - OBJECTIVE: To explore the effects of interventions given to improve pregnancy outcome in women with antiphospholipid antibodies. DATA SOURCES: Cochrane Controlled Trials Register, Cochrane Collaboration Pregnancy and Childbirth Group's Specialized Register of Controlled Trials, EMBASE, and MEDLINE were searched in December 1999. STUDY SELECTION: Randomized or quasi-randomized controlled trials of therapy for pregnancy loss associated with antiphospholipid antibodies were identified. TABULATION, INTEGRATION, AND RESULTS: Trial selection, data extraction, and quality assessment were performed by two authors independently. Quantitative analysis of summary data was performed using the fixed- and random-effects models with heterogeneity assessments. Pregnancy loss and adverse neonatal outcomes were the main outcome measures. Ten trials (n = 627) fulfilled the inclusion criteria (of which four lacked adequate allocation concealment). Three trials of aspirin alone showed no significant reduction in pregnancy loss (relative risk [RR] 1.05, 95% confidence interval [CI] 0.66, 1.68). Heparin combined with aspirin (two trials, 140 patients) significantly reduced pregnancy loss compared with aspirin alone (RR 0.46, 95% CI 0.29, 0.71). Prednisone and aspirin resulted in a significant increase in prematurity (RR 4.83, 95% CI 2.85, 8.21) but no significant reduction in pregnancy loss (RR 0.85, 95% CI 0.53, 1.36). CONCLUSION: Combination therapy with aspirin and heparin may reduce pregnancy loss in women with antiphospholipid antibodies by 54%. Further large, randomized controlled trials with adequate allocation concealment are necessary to exclude significant adverse effects. PMID- 11777525 TI - Labor induction with 25 microg versus 50 microg intravaginal misoprostol: a systematic review. AB - OBJECTIVE: To systematically review published randomized controlled trials (RCTs) to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify RCTs of misoprostol for cervical ripening and labor induction, which compared repeated doses of 25 microg and 50 microg. STUDY SELECTION: We evaluated, abstracted data, and assessed the quality of RCTs to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. TABULATION, INTEGRATION, AND RESULTS: Five RCTs met inclusion criteria for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome (random- and fixed-effects models). In addition, we aggregated the results of two separate studies, permitting an indirect comparison of the two doses being analyzed. In the meta-analysis, tachysystole and hyperstimulation syndrome appear to occur less frequently among women who received 25 microg of misoprostol than with 50 microg. However, neonatal outcomes appear to be comparable with the two doses. Regarding efficacy, use of the 50-microg dose was associated with a shorter interval to vaginal delivery, greater proportion of deliveries within 24 hours, and less frequent need for oxytocin augmentation. The indirect comparison of two studies yielded similar results. CONCLUSION: Published data indicate that intravaginal misoprostol at doses of 50 microg for cervical ripening and labor induction is more efficacious but it is unclear whether it is as safe as the 25-microg dose. PMID- 11777526 TI - Lawson Tait: the forgotten gynecologist. AB - The development of gynecology as a specialty, although primarily American in origin, was influenced in large degree by Robert Lawson Tait, a brilliant Scottish/English surgeon who practiced in the late 19th century. Tait, a self proclaimed gynecologist, is perhaps most widely known as the first to perform salpingectomy to treat ruptured tubal pregnancy. He was also the first to record removal of an ovary for relief of pelvic pain and to induce menopause, perform salpingectomy for the treatment of tubal disease, and develop the technique of transverse transperineal repair of low rectovaginal fistulas. His scrupulous cleanliness was undoubtedly the forerunner of our modern aseptic methods. Tait's bold, innovative surgical techniques led to a significant decrease in surgical mortality, and his prescient, aggressive approach was at the forefront of changes in the practice of obstetrics, which resulted in a marked decrease in maternal morbidity and mortality. This master teacher, whose contributions inspired the next great generation of abdominal and pelvic surgeons, deserves greater recognition within our specialty. PMID- 11777527 TI - ACOG Committee opinion. Number 266, January 2002 : placenta accreta. AB - The incidence of placenta accreta has increased 10-fold in the past 50 years and now occurs with a frequency of 1 per 2,500 deliveries. Women who have had two or more cesarean deliveries with anterior or central placenta previa have nearly a 40% risk of developing placenta accreta. If the diagnosis or strong suspicion of placenta accreta is formed before delivery, the patient should be counseled about the likelihood of hysterectomy and blood transfusion. Blood products and clotting factors should be available. Cell saver technology should be considered if available as well as the appropriate location and timing for delivery to allow access to adequate surgical personnel and equipment. A preoperative anesthesia assessment should be obtained. PMID- 11777528 TI - ACOG Committee opinion. Number 267, January 2002: exercise during pregnancy and the postpartum period. AB - The physiologic and morphologic changes of pregnancy may interfere with the ability to engage safely in some forms of physical activity. A woman's overall health, including obstetric and medical risks, should be evaluated before prescribing an exercise program. Generally, participation in a wide range of recreational activities appears to be safe during pregnancy; however, each sport should be reviewed individually for its potential risk, and activities with a high risk of abdominal trauma should be avoided during pregnancy. Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity. In the absence of either medical or obstetric complications, 30 minutes or more of moderate exercise a day on most, if not all, days of the week is recommended for pregnant women. PMID- 11777529 TI - Expression of the bovine high affinity IL-12 receptor beta2. AB - Four fragments of the bovine IL-12 receptor beta2 were sequenced following generation by reverse transcriptase polymerase chain reaction (RT-PCR) amplification of RNA from mitogen-activated bovine peripheral blood mononuclear cells (PBMC). Primers were based on sequences within regions of the human IL 12Rbeta2 gene that displayed high levels of similarity with the mouse IL-12Rbeta2 gene sequence. The amplified bovine IL-12Rbeta2 fragments had 82-87% similarity at the nucleotide level with human IL-12Rbeta2 and 70-88% similarity at the predicted amino acid level. Bovine IL-12Rbeta2 gene expression was induced following culture of PBMC with Concanavalin A (Con A), with immobilized monoclonal antibody to CD3 or with human recombinant IL-12 p70 and correlated with interferon-gamma (IFN-gamma) production. Expression of bovine IL-12Rbeta2 by PBMC was detected by 2h of culture with Con A and sustained for at least 5 days when cultured with rHuIL-12. Expression, however, did not require cellular proliferation since IL-12 did not induce proliferation, although both Con A and anti-CD3 monoclonal antibody did do so. Addition of rHuIL-10 inhibited IFN-gamma production without abrogating bovine IL-12Rbeta2 gene expression. PMID- 11777530 TI - Peripheral blood mononuclear cell responses to major and minor Dermatophagoides allergens in canine atopic dermatitis. AB - Atopic dermatitis is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans. Most cases involve hypersensitivity to the house dust mites (HDM) Dermatophagoides farinae and Dermatophagoides pteronyssinus. Human atopic dermatitis is associated with the HDM derived allergens Der f 1 and 2, and Der p 1 and 2. Serological data, however, suggest that a 98/104kD protein is the most important allergen in dogs with atopic dermatitis. The aim of this study was to characterise the specificity of circulating T-cells in canine atopic dermatitis for HDM derived allergens. Peripheral blood mononuclear cells (PBMCs) from dogs with atopic dermatitis that were skin test positive for D. farinae and D. pteronyssinus were cultured with crude extracts of D. farinae, D. pteronyssinus and D. microceras, a 98/104kD allergen purified from D. farinae, Der f 1 and Der f 2. There was significantly greater responsiveness of PBMCs to the D. farinae and D. pteronyssinus extracts compared to the D. microceras extract, and similarly to the purified 98/104kD allergen compared to Der f 1 and Der f 2. The close association between serological findings and PBMC proliferation implies that the 98/104kD HDM protein is a major target of immune recognition and that T-cells also participate in the pathogenesis of canine atopic dermatitis by supporting IgE production. PMID- 11777531 TI - Protective immunity induced by DNA vaccination of channel catfish with early and late transcripts of the channel catfish herpesvirus (IHV-1). AB - Seven full-length transcripts encoding four early and three late genes of the channel catfish virus (CCV), ictalurid herpesvirus I (IHV-1), have been cloned following rt-PCR amplification and DNA sequencing. Transcripts were selected based on their predicted association with membrane structures, identification as an envelope glycoprotein, or as a viral capsid protein. The transcripts derived from ORF 6, ORF 7, ORF 8a, ORF 10, ORF 51, ORF 53, and ORF 59 were all shown to be complete and unspliced. Each of the seven ORFs was cloned into a vaccine expression vector designed to support high levels of expression of the inserted sequence in catfish tissues. Solutions of DNA containing one each of the seven CCV ORFs, vector alone or PBS were injected intramuscularly into 4-8 cm catfish. Four to 6 weeks after injection each experimental group was challenged with one LD(50) of CCV. Single injections of DNA expression constructs containing ORF 59, encoding the envelope glycoprotein, or ORF 6, encoding a presumptive membrane protein, were found to elicit the strongest resistance to challenge compared to uninjected, PBS injected or vector injected groups. Even more effective was a combination vaccine pair in which both ORF 59 and ORF 6 expression constructs were injected. Other ORFs did not provide consistent protection to challenge above that observed in control fish. Both percent survival and kinetics of cumulative deaths were improved using the combination DNA vaccine encoding ORF 6 and ORF 59. Both ORF 6 and ORF 59 were able to elicit virus neutralizing antibodies capable of an anamnestic response on viral challenge. We believe this evidence provides adequate proof of principle for the use of DNA vaccines in channel catfish and the effectiveness of the resistance to viral infection they elicit. PMID- 11777532 TI - IgG antibody responses to an inhaled antigen in horses with "heaves" (recurrent airway obstruction). AB - A controlled experimental system for the evaluation of pulmonary immune responses in horses with "heaves" (recurrent airway obstruction) has been developed. We hypothesized that the humoral immune response to an inhaled antigen in diseased horses would be different from that of healthy horses and that chronic pulmonary inflammation would bias the production of IgG isotypes in diseased horses as compared to healthy horses. Healthy and affected horses were housed in a natural challenge environment (stabled, fed dusty hay) and exposed by inhalation, to a nebulized solution of keyhole limpet hemocyanin (KLH). Sera and bronchoalveolar lavage fluids (BALFs) were collected from horses prior to and following their inhalation exposure to the antigen. Differential cell counts were performed on the cells in the BALF. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of IgGa, IgGb, IgG(T) and combined IgG specific for KLH in the sera and BALF. The percentages of neutrophils in the BALF of diseased horses were increased 4-6-fold over healthy horses. Combined IgG specific for KLH was significantly greater in BALF and serum from healthy compared to diseased horses. Differences in isotypes were also evident; however, only IgGb specific for KLH in the BALF was significantly increased in healthy versus diseased horses. Possible explanations for this difference include: (1) increased destruction of antigen before it could interact with lymphocytes, (2) down regulation of IgGb production by inhibitory cytokines in diseased horses, or (3) binding of IgGb to Fc receptors on the large numbers of neutrophils in the lungs of diseased horses. In contrast to the prevailing notion that horses with heaves have exaggerated immune responses, our data suggest that diseased horses exposed to an aerosolized protein mount weaker IgG responses compared to healthy horses. PMID- 11777533 TI - Polymorphic expression in the CD8alpha chain surface receptor of African lions (Panthera leo). AB - Free-ranging African lion (Panthera leo) peripheral blood mononuclear cells (PBMC) were examined using flow cytometry and antibodies developed for use in the domestic cat to determine if phenotypic changes occurred in lion lymphocytes as a result of feline immunodeficiency virus (FIV) infection. The percentage of CD8 cells from lion peripheral blood was considerably lower than in the domestic cat. Lions with elevated levels of CD8+ cells were typically infected with FIV, similar to observations in the domestic cat. Antibodies against the alpha chain of the CD8 receptor (monoclonal antibody (mAb) 3.357) did not react consistently in all lions examined. Flow cytometric analysis determined that approximately 82 and 80% of the animals from Kruger and Hluhluwe-Umfolozi National Parks in South Africa reacted with the monoclonal antibody against the alpha chain of CD8 receptor, while only 17% of the lions in Etosha National Park in Namibia cross reacted with the CD8alpha chain. There was no apparent correlation between FIV status and CD8alpha chain reactivity. The relative isolation of Etosha from the other two parks could explain the marked difference in CD8alpha chain expression and suggests that lions similar to other mammalian species demonstrate polymorphic expression of the CD8alpha chain (197). PMID- 11777534 TI - Differential expression of inducible nitric oxide synthase is associated with differential Toll-like receptor-4 expression in chicken macrophages from different genetic backgrounds. AB - The purpose of this study was to examine iNOS gene expression and activity in macrophages from different chicken genetic lines against various bacterial LPS. Furthermore, the possible involvement of surface LPS receptors as candidates for differential iNOS gene induction in these genetic lines of chicken was also examined. Sephadex-elicited abdominal macrophages (1 x 10(6)) as well as iNOS hyper-responder macrophages from a transformed chicken macrophage cell line, MQ NCSU, were exposed to 5 microg/ml LPS from E. coli, Shigella flexneri, Serratia marcensces, and Salmonella typhimurium. Nitrite levels were quantitated in the culture supernatant fractions of macrophages after 24h by the Griess method. The results showed that macrophages from K-strain (B(15)B(15)) (range from two separate trials: 31-89 microM) and MQ-NCSU (22-81 microM) were high responders whereas macrophages from both GB1 (B(13)B(13)) (15-38 microM) and GB2 (B(6)B(6)) (7-15 microM) chickens were low responders against all LPSs used. Northern blot analysis revealed that K-strain macrophages expressed higher intensity of 4.5Kb iNOS mRNA (iNOS/beta-actin ratio) than macrophages from GB2 regardless of the LPS source. To elucidate possible molecular mechanism(s) involved in iNOS gene expression in these two strains of chickens, the constitutive expression of LPS related macrophage cell surface receptors, CD14, Toll-like receptor-2 (TLR2), and Toll-like receptor-4 (TLR4), was examined via flow cytometry using anti-human CD14, TLR2 and TLR4 antibodies. CD14 surface expression and intensity was not different between macrophages from K-strain or GB2 chickens. In contrast, while the overall percentage of TLR4-positive macrophages was the same (K-strain, trial 1=92%, trial 2=62%; GB2, trial 1=91%, trial 2=64%), the mean fluorescence intensity (MFI), an indicator of receptor number, was significantly higher (P=0.05) in K-strain macrophages (MFI: trial 1=145; trial 2=131) than GB2 macrophages (MFI: trial 1=101; trial 2=98). Furthermore, TLR2 (a previously thought candidate as LPS signaling molecule) positive cell numbers were higher in K-strain than the GB2 macrophages in one of the two trials with no difference in the intensity of TLR2 expression in either trial. These findings suggest that the observed differences in iNOS expression and activity among the K-strain (hyper responder) and GB2 (hypo-responder) chickens are, at least in part, due to differential expression of TLR4 (an LPS signaling molecule), leading to more intense LPS-mediated activation of K-macrophages. PMID- 11777535 TI - Monoclonal antibodies to lymphocyte surface antigens for cetacean homologues to CD2, CD19 and CD21. AB - CD2 is a pan-T cell marker, while CD19 and CD21 are important molecules in signal transduction of B lymphocytes. CD19 and CD21 are both present on mature B cells, while CD19 is also present in developing B cells and plasma cells. Monoclonal antibodies (mAbs) against cetacean lymphocyte putative homologues to CD2 (two different antibodies), CD19 and CD21 were characterized. The proteins immunoprecipitated were as follows: F21.I (putative anti-CD2), 43 and 59kDa; F21.B (putative anti-CD19), 83 and 127kDa; F21.F (putative anti-CD21), 144kDa. The second putative anti-CD2 (F21.C) selectively inhibited the binding of F21.I. Both the putative anti-CD2 (T cell markers) stained T-cell zones on lymph node sections, while both the B cell markers (putative CD19 and CD21) stained B-cell zones. F21.B and F21.F were absent from thymus single cell suspension but labeled 63 and 65% mesenteric lymph node lymphocytes, respectively, while both F21.C and F21.F were present on 100% thymocytes and fewer lymph node lymphocytes. B and T cell markers were mutually exclusive on double labeling using flow cytometry. These mAbs are foreseen as possible valuable diagnostic and research tools to assess immune functions of captive and wild cetaceans. PMID- 11777536 TI - CpG oligodeoxynucleotides stimulate canine and feline immune cell proliferation. AB - Oligodeoxynucleotides (ODNs) with unmethylated CpG dinucleotide motifs may be useful as non-specific immune system stimulants and adjuvants for protein or nucleic acid vaccines in humans and other primates. They may also be useful in cancer immunotherapy and in the modulation of allergic responses or mucosal immunity. To begin to determine the potential utility of CpG ODN technology in small animal veterinary medicine, we developed procedures to analyze the effects of CpG ODN on canine and feline blood, spleen and lymph node (LN) cells. We find that certain CpG ODN cause good lymphocyte proliferation (as monitored by [(3)H] thymidine incorporation) in both canine and feline spleen and LN cells, but not in blood. This overall stimulatory effect of CpG ODN on spleen and LN cells is CpG dependent. The reverse sequences, GpC ODNs, do not cause significant lymphocyte proliferation in the cat; however, dogs are more sensitive to stimulation by the non-specific immune effects of the phosphorothioate backbone. We conclude that unmethylated CpG ODNs may also have potential uses as immune stimulants for vaccines and other antimicrobial agents in veterinary medicine for companion animals. PMID- 11777537 TI - IL-4 and IL-10 inhibition of IFN-gamma- and TNF-alpha-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites. AB - The requirement for IFN-gamma and/or TNF-alpha as co-stimulants with Babesia bovis merozoites for nitric oxide (NO) production was examined, as well as the regulatory role of IL-4 and IL-10. Purified B. bovis merozoites did not induce the production of NO in undifferentiated monocytes without addition of exogenous IFN-gamma and TNF-alpha unless the monocytes taken ex vivo were producing TNF alpha endogenously. Under the latter condition, the NO production resulting from merozoite stimulation remained IFN-gamma-dependent. There was no evidence for endogenous synthesis of TNF-alpha in monocyte-derived macrophages (MDM), and merozoites alone were incapable of inducing TNF-alpha mRNA in MDM. However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced. Both IL-4 and IL-10 inhibited expression of iNOS and production of NO in merozoite-stimulated monocytes. PMID- 11777538 TI - The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis. AB - The perivascular (PVM) and meningeal (MM) macrophages constitute a major population of resident macrophages in the central nervous system (CNS). To investigate a possible role of PVM and MM during CNS inflammation, we have analysed PVM and MM during experimental allergic encephalomyelitis (EAE), an experimental model for MS, in the rat. Our results demonstrate a remarkable increase in the expression of the ED2 antigen on PVM and MM (already at day 9 post-EAE induction), which precedes the onset of clinical symptoms and infiltration of leukocytes into the CNS (at day 13). Therefore, the onset of EAE is accompanied by alterations of PVM and MM, and the ED2 antigen provides an early marker of pathology during CNS inflammation. Moreover, selective depletion of the ED2-positive macrophages in the CNS using clodronate liposomes resulted in a suppression of the clinical symptoms. These observations indicate that PVM and MM play a role during the early stages of EAE development. PMID- 11777539 TI - IL-10 promotes survival of microglia without activating Akt. AB - IL-10 is an anti-inflammatory cytokine that has recently been shown to promote survival of neurons and glia. Here we establish that IL-10 induces phosphorylation of Stat3 on Tyr(705) and serves as a survival factor for N13 microglial cells. Recombinant IL-10 (10 ng/ml) decreases growth factor withdrawal induced apoptosis by 50%, as assessed by TUNEL. In contrast to IL-10, IGF-I increases enzymatic activity of PI 3-kinase and causes phosphorylation on serine(473) of Akt but does not prevent microglial apoptosis. These data establish that IL-10 activates Stat3 and inhibits the mitochondrial pathway of cell death without activating the Akt cell survival pathway. PMID- 11777540 TI - Encephalitogenic and immunogenic potential of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase) in ABH and SJL mice. AB - Synthetic peptides of myelin-associated glycoprotein (MAG), oligodendrocyte specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were screened for their ability to induce experimental allergic encephalomyelitis (EAE) in ABH (H-2A(g7)) and SJL (H-2(s)) mice. The use of overlapping 16mer MAG peptides identified residues 97-112 as a T-cell and encephalitogenic epitope in ABH mice which induced clinical and histological signs of acute EAE. Immunization of SJL mice with MAG peptides failed to induce disease whereas immunization of SJL mice with synthetic peptides of OSP induced major T-cell responses to OSP 73-88 and 81-96. Another epitope, OSP 57-72, that induced EAE, failed to induce T-cell responses in mice immunised with peptides based on the whole sequence supporting a role for cryptic epitopes. In comparison, whilst immunization of ABH mice with OSP revealed two immunodominant T-cell epitopes (49-64 and 137-152), an encephalitogenic epitope was not identified. Similarly, immunization of both SJL and ABH mice with CNPase peptides induced T-cell responses to several epitopes. However, these were not encephalitogenic. This study is the first to identify an encephalitogenic epitope of MAG and immunodominant epitopes of MAG, OSP and CNPase in SJL and ABH mice. The ability of both cryptic and noncryptic peptide epitopes of these myelin antigens to initiate EAE suggests that mice at least are not tolerant to some regions of MAG and OSP and that such specific autoimmune responses may play an important role in the pathogenesis of immune-mediated neurological diseases such as multiple sclerosis. PMID- 11777541 TI - Dopamine suppresses IL-12 p40 production by lipopolysaccharide-stimulated macrophages via a beta-adrenoceptor-mediated mechanism. AB - In this study, we examined the effect of dopamine on the production of IL-12 p40 by lipopolysaccharide (LPS)-stimulated J774.1 macrophages and mouse peritoneal macrophages. Treatment of J774.1 cells with dopamine (0.01-100 microM) decreased the release of IL-12 p40, in a concentration-dependent manner. The attenuating effect of dopamine on IL-12 p40 production appeared to be pretranslational, because dopamine decreased mRNA accumulation of IL-12 p40. The inhibitory effect of dopamine on IL-12 p40 production by J774.1 macrophages was not mediated by dopamine receptors, because dopamine receptor antagonists were unable to reverse the dopamine-induced suppression of IL-12 p40 production. Since the beta adrenoceptor antagonist propranolol completely prevented the inhibitory effect of dopamine on IL-12 p40 production, the suppressive effect of dopamine on IL-12 p40 production by J774.1 cells is mediated by beta-adrenoceptors. In contrast to J774.1 cells, propranolol only partially reversed the inhibitory effect of dopamine on IL-12 production by peritoneal macrophages. Furthermore, dopamine stimulated the production of the anti-inflammatory cytokine IL-10 in both J774.1 cells and peritoneal macrophages. While the stimulatory effect of dopamine on IL 10 production by J774.1 cells was beta-adrenoceptor-mediated, dopamine increased IL-10 production by peritoneal macrophages via both beta-adrenoceptor-dependent and independent mechanisms. These results indicate that dopamine has multiple anti-inflammatory effects mediated by both beta-adrenoceptor dependent and independent mechanisms. PMID- 11777542 TI - Mononuclear phagocyte biophysiology influences brain transendothelial and tissue migration: implication for HIV-1-associated dementia. AB - Mononuclear phagocyte (MP) brain migration influence neuronal damage during HIV-1 associated dementia (HAD). We demonstrate that potassium channels, expressed in human monocyte-derived macrophages (MDM), are vital for MP movement through Boyden chemotactic chambers, an artificial blood-brain barrier and organotypic hippocampal brain slices. MDM migration is inhibited by voltage-and calcium activated potassium channel blockers that include charybodotoxin, margatoxin, agatoxin and apamin. This is observed both in uninfected and HIV-1-infected MP. The results suggest that potassium channels affect MDM brain migration through altering cell volume and shape. Such mechanisms likely affect MP-induced neuronal destruction during HAD. PMID- 11777543 TI - GROalpha/KC, a chemokine receptor CXCR2 ligand, can be a potent trigger for neuronal ERK1/2 and PI-3 kinase pathways and for tau hyperphosphorylation-a role in Alzheimer's disease? AB - Inflammation has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases. We have examined the potential role of some chemokine/chemokine receptors in this process. It is known that CXCR2 is a strongly expressed chemokine receptor on neurons and is strongly upregulated in AD in a subpopulation of neuritic plaques. Here, we show that one of the CXCR2 ligand GROalpha/KC can be a potent trigger for the ERK1/2 and PI-3 kinase pathways, as well as tau hyperphosphorylation in the mouse primary cortical neurons. GROalpha immunoreactivity can be detected in a subpopulation of neurons in normal and AD. Therefore, the CXCR2-ligand pair may have a potent pathophysiological role in neurodegenerative diseases. PMID- 11777544 TI - Differentiated Th1 autoreactive effector cells can induce experimental autoimmune encephalomyelitis in the absence of IL-12 and CD40/CD40L interactions. AB - IL-12 plays a critical role in the priming of Th1 responses to bacterial/parasitic antigens and autoantigens. Several studies have demonstrated a dependency on CD40/CD40L interactions and IL-12 for maintenance of both antibacterial/parasitic and autoreactive Th1 cells in vivo. However, it is still unclear if fully differentiated Th1 effectors require continued stimulation by IL 12. We demonstrate that the proliferative response and IFN-gamma production by a fully differentiated T cell line specific for myelin oligodendrocyte glycoprotein are completely independent of IL-12 and CD40/CD40L interactions. The capacity of this line to adoptively transfer experimental autoimmune encephalomyelitis is also independent of IL-12 and CD40/CD40L. These results have important implications regarding the therapeutic usefulness of blockade of IL-12 or the CD40/CD40L pathway for treatment of autoimmune disease. PMID- 11777545 TI - Interferon regulatory factor-1 is required for interferon-gamma-induced MHC class I genes in astrocytes. AB - Recent studies have shown that the role of the transcription factor interferon regulatory factor-1 (IRF-1) in the expression of major histocompatibility complex (MHC) class I molecules is tissue-specific. Our previous studies indicated a role for IRF-1 in expression of MHC class I genes in cultured astrocytes in response to interferon-gamma (IFN-gamma). However, the requirement for IRF-1 in MHC class I expression has not been directly analyzed in neural tissue. To further ascertain the importance of IRF-1 in the induction of MHC class I genes in astrocytes in response to IFN-gamma, we analyzed astrocytes from mice with a targeted disruption of the IRF-1 gene (IRF-1(-/-) mice). As expected, astrocytes from wild type (IRF-1(+/+)) mice showed a coordinate increase in both IRF-1 and MHC class I gene expression in response to IFN-gamma. To the contrary, astrocytes from IRF-1(-/-) mice had greatly reduced MHC class I mRNA expression. MHC class I gene promoter activity in astrocytes was controlled entirely through a single enhancer, the MHC-IRF-E, to which IRF-1 bound in response to IFN-gamma in wild type but not in IRF-1(-/-) mouse astrocytes. In vivo, astrocytes in brains of wild type mice readily responded to IFN-gamma to express MHC class I molecules. This correlated with increased MHC class I mRNA in the brain. In contrast, brains of IRF-1(-/-) mice showed no MHC class I gene induction following exposure to IFN gamma indicating that all cells in the central nervous system (CNS) including astrocytes with the potential to express MHC class I molecules were dependent on IRF-1. These studies conclusively demonstrate a major role for IRF-1/MHC-IRF-E interactions in controlling MHC class I gene expression in astrocytes in response to IFN-gamma. PMID- 11777546 TI - Tumor necrosis factor receptor p55 and p75 deficiency protects mice from developing experimental autoimmune myasthenia gravis. AB - The precise pathogenic role of proinflammatory cytokines belonging to the tumor necrosis factor (TNF) family has not been investigated yet in antibody-mediated myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG). In this study we report that TNF receptor p55(-/-) p75(-/-) mice were resistant to the development of clinical EAMG induced by acetylcholine receptor (AChR) immunizations. The resistance was associated with reduced serum levels of IgG, IgG(1), IgG(2a), and IgG(2b) anti-AChR antibody isotypes. However, IgM anti-AChR antibodies were not reduced, suggesting defective anti-AChR IgG class switching in TNF receptor p55(-/-) p75(-/-) mice. We thus demonstrate the genetic evidence for the role of TNF receptor p55 and p75 in EAMG pathogenesis, and their requirement for the generation of anti-AChR IgG antibodies. PMID- 11777547 TI - IL-1 genes in myasthenia gravis: IL-1A -889 polymorphism associated with sex and age of disease onset. AB - Myasthenia gravis (MG) is a multifactorial autoimmune disease of the neuromuscular junction. We investigated the relation between four polymorphisms of the interleukin (IL)-1 gene cluster on 2q12-22, and MG susceptibility and clinical features in a large cohort of individuals. No polymorphism was associated with MG susceptibility. However, the IL-1A -889 CC genotype was associated with early disease onset (p=0.0044) in the whole MG group and the subgroup of CC males developed MG about 18 years earlier than males carrying other IL-1A -889 genotypes (p=0.022). This finding suggests that IL-1A is a disease modifier in MG, or is in linkage disequilibrium with an unknown locus on chromosome 2. PMID- 11777548 TI - Oligoclonal T-cells in blood and target tissues of patients with anti-Hu syndrome. AB - T-cell clones of unknown significance (TCUS), assessed by monoclonal or oligoclonal T-cell patterns in PCR-DGGE, were detected in blood of 7/9 patients with anti-Hu syndrome. Clonal patterns were also detected in 2/2 neoplastic lymph nodes, and in 2/2 inflamed dorsal root ganglia from three patients. Only some T cell clones found in target tissues were also detected in blood or non-target tissues, and likely corresponded to TCUS. In one patient, an identical T-cell clone was found in both neoplastic lymph node tissue and dorsal root ganglia, but not in blood. Dorsal root-infiltrating lymphocytes were cytotoxic CD8(+) TIA-1(+) T-cells. They were often found in close contact to sensory neurons, most of which expressed MHC-1. Taken together, these data support a direct effector role of cytotoxic CD8(+) T-cells, the same clones being likely operative in sensory neuron damage and immune-mediated tumor growth control. PMID- 11777549 TI - Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections. AB - Dendritic cells (DC) accumulate in the CNS during inflammation and may contribute to local immune responses. Two DC subsets present in human cerebrospinal fluid (CSF) are probably recruited from myeloid (CD11c(+)CD123(dim)) and plasmacytoid (CD11c(-)CD123(high)) blood DC. In bacterial meningitis and especially in Lyme meningoencephalitis, numbers of myeloid and plasmacytoid DC in CSF were increased, compared to non-inflammatory neurological diseases, and correlated with chemotactic activity of CSF for immature monocyte-derived DC (moDC). Multiple DC chemoattractants, including macrophage inflammatory protein (MIP) 1beta, monocyte chemotactic protein (MCP)-1, MCP-3, RANTES and stromal cell derived factor (SDF)-1alpha were elevated in CSF in these two neuroinfections. Chemotaxis of immature moDC induced by these CSFs could be partially inhibited by mAbs against CXCR4, the receptor for SDF-1alpha, and CD88, the receptor for C5a. SDF-1alpha present in CSF also chemoattracted mature moDC, which in vivo could correspond to a diminished migration of antigen-bearing DC from the CSF to secondary lymphoid organs. Regulation of DC trafficking to and from the CSF may represent a mechanism of controlling the CNS inflammation. PMID- 11777550 TI - Induction of TRAIL-mediated glioma cell death by human T cells. AB - Among the death ligands of the tumor necrosis factor/nerve growth factor (TNF/NGF) superfamily, TNF-related apoptosis-inducing ligand (TRAIL) is considered to play a unique role due to its binding to both apoptosis-inducing and -blocking membranous receptors, apoptosis-independent effects and distinct species differences. Here, we demonstrate that human antigen-specific T helper cells upon activation are capable of directly lysing glioma cell lines via TRAIL receptor/TRAIL interactions. Out of 17 T cell lines, nine showed predominantly TRAIL-mediated killing of glioma cell lines compared to CD95 ligand- or TNF induced cell death. The cytotoxic potential of the T cell lines was independent of T helper differentiation, antigen specificity and donor source. Thus, TRAIL mediated signaling is involved in T cell cytotoxicity towards glioma cell lines, which might play an important role in tumor regression. PMID- 11777552 TI - Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability. AB - The pathologic basis of disease progression in multiple sclerosis (MS) is thought to involve axonal degeneration, which contributes to the accumulation of neurological disability. Recent reports suggest that intrathecal concentrations of the neurofilament protein in relapsing remitting MS correlate with disease activity and the degree of disability. We sought to investigate the intrathecal levels of other cytoskeletal components of axons, primarily actin, tubulin and the light subunit of neurofilament (NFL) in patients with progressive MS and relevant controls and correlate results with clinical parameters of disease severity. Cerebrospinal fluid (CSF) concentrations of actin, tubulin and NFL were significantly increased in MS patients when compared to corresponding levels in patients with other inflammatory or non-inflammatory neurological diseases. Moreover, the intrathecal release of actin and tubulin, and to a lesser extent NFL, was significantly more marked in patients with primary and secondary progressive MS when compared to patients with relapsing remitting disease and was correlated with clinical disability. Our findings suggest that progressive MS is associated with the heightened intrathecal release of axonal cytoskeletal proteins, and that CSF actin, tubulin and NFL are reliable markers of axonal damage. PMID- 11777551 TI - Chemokine receptor expression on B cells and effect of interferon-beta in multiple sclerosis. AB - We investigated the B-cell expression of chemokine receptors CXCR3, CXCR5 and CCR5 in the blood and cerebrospinal fluid (CSF) from patients in relapse of multiple sclerosis (MS) and in neurological controls. Chemokine receptor expression was also studied in interferon-beta-treated patients with relapsing remitting or secondary progressive MS. We observed significantly higher expression of CXCR3 on B cells in the CSF in active MS than in controls. Patients with active MS also had higher B-cell expression of CCR5 in blood. No major differences between RRMS and SPMS patients were detected, and chemokine receptor expression was not affected by interferon-beta treatment. PMID- 11777553 TI - HLA class II associated risk and protection against multiple sclerosis-a Finnish family study. AB - We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was DRB1*15-DQB1*0602 (P<10(-6)) as expected and a weak predisposing effect of DRB1*04-DQB1*0302 was revealed after the elimination of DRB1*15-DQB1*0602. HLA DRB1*01-DQB1*0501 and DRB1*13-DQB1*0603 were negatively associated with MS in transmission disequilibrium test, but only the DRB1*13-DQB1*0603 association remained significant (P=0.008) after the elimination of DRB1*15-DQB1*0602 haplotypes. Based on this study HLA class II haplotypes exhibit both predisposing and protective effects in MS. PMID- 11777554 TI - Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain. AB - Emerging data indicate that chemokine receptors on neurons and glia in the central nervous system (CNS) play a role in normal CNS development, intercellular communication, and the neuropathogenesis of AIDS. To further understand chemokine receptors in the brain and explore their potential role in HIV neuropathogenesis, particularly in pediatrics, we examined the regional and cellular distribution of CCR5 and CXCR4 in normal fetal, neonatal, and adult rhesus macaques. CCR5 and CXCR4 were detected by immunohistochemistry and immunofluorescence within the cytoplasm of subpopulations of neurons in the neocortex, hippocampus, basal nuclei, thalamus, brain stem, and cerebellum and by flow cytometry on the surface of neurons and glia. Interestingly, expression of CCR5 and CXCR4 increased significantly (p<0.05) from birth to 9 months of age. We further characterize this dynamic developmental pattern of CCR5 and CXCR4 expression in resident cells of the CNS. PMID- 11777555 TI - Disease activity in multiple sclerosis correlates with T lymphocyte expression of the inhibitor of apoptosis proteins. AB - The pathogenesis of multiple sclerosis (MS) is thought to involve failure of programmed cell death (apoptosis) to eliminate potentially pathogenic, autoreactive T lymphocytes. This failure may be caused by multiple abnormalities of the cell death machinery. The inhibitors of apoptosis (IAP) proteins are central regulators of cell death that inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the dynamics of cellular IAP-1, IAP-2, and X-linked IAP, in resting and mitogen stimulated T lymphocytes from MS patients and relevant controls. The expression of IAP proteins was significantly higher in mitogen stimulated T lymphocytes from patients with clinically active MS when compared to corresponding expressions from patients with stable MS or from other controls. Heightened expression of IAP proteins in patients with active MS correlated with clinical features of disease activity, and with T lymphocyte resistance to apoptosis. In contrast, cellular expression of the anti apoptosis protein Bcl-2 did not differ between active and stable MS, and was relatively similar between MS patients and controls. These findings suggest that overexpression of IAP proteins in stimulated T lymphocytes is a feature of clinically active multiple sclerosis. PMID- 11777556 TI - Prolonged intrathecal release of soluble Fas following severe traumatic brain injury in humans. AB - The mechanisms underlying cell death following traumatic brain injury (TBI) are not fully understood. Apoptosis is believed to be one mechanism contributing to a marked and prolonged neuronal cell loss following TBI. Recent data suggest a role for Fas (APO-1, CD95), a type I transmembrane receptor glycoprotein of the nerve growth factor/tumor necrosis factor superfamily, and its ligand (Fas ligand, FasL) in apoptotic events in the central nervous system. A truncated form of the Fas receptor, soluble Fas (sFas) may indicate activation of the Fas/FasL system and act as a negative feedback mechanism, thereby inhibiting Fas mediated apoptosis. Soluble Fas was measured in cerebrospinal fluid (CSF) and serum of 10 patients with severe TBI (GCS< or =8) for up to 15 days post-trauma. No sFas was detected in CSF samples from patients without neurological pathologies. Conversely, after TBI 118 out of 120 CSF samples showed elevated sFas concentrations ranging from 56 to 4327 mU/ml. Paired serum samples showed above normal (8.5 U/ml) sFas concentrations in 5 of 10 patients. Serum levels of sFas were always higher than CSF levels. However, there was no correlation between concentrations measured in CSF and in serum (r(2)=0.078, p=0.02), suggesting that the concentrations in the two compartments are independently regulated. Also, no correlation was found between sFas in CSF and blood brain barrier (BBB) dysfunction as assessed by the albumin CSF/serum quotient (Q(A)), and concentrations of the cytotoxic cytokine tumor necrosis factor-alpha in CSF, respectively. Furthermore, there was no correlation with two markers of immune activation (soluble interleukin-2 receptor and neopterin) in CSF. Maximal CSF levels of sFas correlated significantly (r(2)=0.8191, p<0.001) with the early peaks of neuron-specific enolase in CSF (a marker for neuronal cell destruction), indicating that activation of the Fas mediated pathway of apoptosis may be in part the direct result of the initial trauma. However, the prolonged elevation of sFas in CSF may be caused by the ongoing inflammatory response to trauma and delayed apoptotic cell death. PMID- 11777557 TI - Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity. AB - BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS. PMID- 11777558 TI - Treatment of experimental autoimmune myasthenia gravis with recombinant human tumor necrosis factor receptor Fc protein. AB - Lymphotoxin-alpha (TNF-beta) and TNF receptor p55 gene knockout mice are resistant to the development of antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG), suggesting a possible role of TNF in mediating EAMG. Therefore, we tested the hypothesis that blocking the functional interaction of TNF with their receptors by soluble recombinant human TNFR:Fc would suppress the ongoing clinical EAMG. Recombinant human TNFR:Fc administered daily for 2 weeks to C57BL6 mice with ongoing clinical EAMG significantly improved clinical EAMG when compared with placebo-treated mice. A clinical trial of selected myasthenia gravis patients with recombinant human TNFR:Fc could be attempted. PMID- 11777560 TI - Laser desorption mass spectrometry for microbial DNA analysis. AB - Recently, we demonstrated that a matrix-assisted laser desorption/ionization time of-flight mass spectrometer (MALDI-TOF MS) can be used to determine the molecular weight of polymerase chain reaction (PCR) products of intact 16S rRNA regions and to profile their restriction digests. This is the first time that MALDI-TOF MS with ultraviolet (UV) photoionization has been used to analyze a PCR product of approximately 1600 nucleotides in length. PMID- 11777561 TI - Sample preparation of Gram-positive bacteria for identification by matrix assisted laser desorption/ionization time-of-flight. AB - A new sample preparation method was developed for fresh, whole-cell Gram-positive bacteria to be analyzed by matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI ToF MS). With fresh, whole-cell Gram-negative bacteria of the Enterobacteriaceae family, we had previously achieved spectra consisting of >50 peaks and mass ranges of 2-25 kDa. Because similar spectral quantity could not be achieved for Gram-positive bacteria, using this same protocol, we investigated an alternative approach that focuses on the thick peptidoglycan layer of the cell wall. Gram-positive bacteria were incubated with 0.05-0.5 mg/ml lysozyme for 30 min prior to being analyzed by MALDI ToF MS. Lysozyme is an enzymatically stable, 14-kDa protein that specifically cleaves between peptidoglycan disaccharide subunits. A significant increase in overall number of peaks (>50) in the 2-14 kDa range was observed without interference from the presence of lysozyme. We show that for four different species (Staphylococcus aureus, S. haemolyticus, Streptococcus pyogenes, and S. agalactiae) reproducible subset of peaks were found within spectra from a reference strain and two unrelated clinical isolates. The data suggests that this sample preparation may be useful for increasing the overall number of peaks within spectra for subsequent development of bacterial identification strategies. PMID- 11777562 TI - Intact cell mass spectrometry (ICMS) used to type methicillin-resistant Staphylococcus aureus: media effects and inter-laboratory reproducibility. AB - Intact cell mass spectrometry (ICMS) rapidly analyses the surface composition of microorganisms providing rapid, discriminatory fingerprints for identification and subtyping of important nosocomial pathogens such as methicillin resistant Staphylocccus aureus (MRSA). In this study, ICMS using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI TOF/MS) was assessed for the identification and subtyping of MRSA. An intra- and inter laboratory reproducibility study was carried out and the effects of culture media (an important source of variation for ICMS) were also studied. Several media used for the cultural identification of MRSA were examined using a panel of well characterised staphylococcal isolates (n=26). Six MRSA isolates were analysed over a 1-month period for intra-laboratory reproducibility on the same instrument and three different culture media. Spectra were consistent for each isolate between the four experiments on the same culture medium. Individual isolates produced different spectral profiles on different culture media. Spectra from organisms grown on Columbia blood agar contained more peaks (approximately 120) compared to Columbia agar (approximately 50) and methicillin mannitol salt agar (approximately 25). All 26 staphylococcal isolates were subjected to an inter laboratory study on two MALDI instruments. For each isolate, the overall spectral profile was the same for each of the two instruments but the baseline threshold values was adjusted due to instrument differences in detector sensitivities. Differences between certain regions of the spectra reproducibly identified isolates belonging to the two major MRSA strains (EMRSA phage group 15 and 16). These results demonstrate ICMS with appropriate media selection is a rapid and reproducible technique for identification and discrimination of MRSA. PMID- 11777563 TI - Rapid typing of bacteria using matrix-assisted laser desorption ionisation time of-flight mass spectrometry and pattern recognition software. AB - Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) of intact microorganisms, also known as intact cell MALDI-TOF-MS (ICM-MS), has been shown to produce characteristic mass spectral fingerprints of moieties desorbed from the cell surface. ICM-MS spectra can be obtained in minutes after removal of a colony from a culture plate. The similarity of ICM-MS spectra of replicate samples and of two different batches of the same bacterial strain demonstrates, in this study, the reproducibility of the technique. We have developed the Manchester Metropolitan University Search Engine (MUSE) to rapidly build and search databases of ICM-MS spectra. A database of 35 strains, representing 20 species and 12 genera, was built with MUSE and used to identify 212 isolates. The database was created in 26 s and loaded in 10 s, ready for searching, which took less than 1 s per isolate. Correct matches were made in 79%, 84% and 89% of the 212 samples at strain, species and genus levels, respectively. At least 50% of the replicates of 42 of the 45 isolates matched the correct strain, and the most commonly identified species for 43 of the 45 isolates was the correct one. The close match of the Escherichia coli strains containing the O157 antigen and the E. coli strains containing the K1 antigen suggests that these antigens may have a dominating influence on the ICM-MS fingerprints of these strains. We now have the ability to acquire ICM-MS fingerprints of bacteria and to search a database of these fingerprints within minutes, so that the rapid identification of bacteria to the strain level can be realised. PMID- 11777564 TI - Flash detection/identification of pathogens, bacterial spores and bioterrorism agent biomarkers from clinical and environmental matrices. AB - We propose to develop an integrated rapid, semiportable, prototype point microbial detection/identification system for clinical specimens that is also capable of differentiating microbial bioterrorism attacks from threats or hoaxes by defining the pathogen. The system utilizes "flash" extraction/analytical system capable of detection/identification of microbes from environmental and clinical matrices. The system couples demonstrated technologies to provide quantitative analysis of lipid biomarkers of microbes including spores in a system with near-single cell (amol/microl) sensitivity. Tandem mass spectrometry increases specificity by providing the molecular structure of neutral lipids, phospholipids, and derivatized spore-specific bacterial biomarker, 2,6 dipicolinic acid (DPA) as well as the lipopolysaccharide-amide-linked hydroxy fatty acids (LPS-ALHFA) of Gram-negative bacteria. The extraction should take about an hour for each sample but multiple samples can be processed simultaneously. PMID- 11777565 TI - Phospholipid analysis as a tool to study complex microbial communities in marine sediments. AB - To complement information on microbial communities in marine sediments that can be obtained using microbiological methods, we developed an analytical procedure to trace microbial lipids in environmental samples. We focused on analyzing intact phospholipids as these membrane constituents are known to be biomarkers for viable cells. Analysis of intact phospholipids from a fractionated and preconcentrated sediment extract was achieved using liquid chromatography electrospray ionization-mass spectrometry (HPLC-ESI-MS). The combined analysis of phospholipid types and their fatty acid substituents allowed a differentiation between various groups of microorganisms living in the sediment. For comparison three strains of marine sulfate-reducing bacteria (SRB) were analysed for their lipid content. PMID- 11777566 TI - Biomarker techniques to screen for bacteria that produce polyunsaturated fatty acids. AB - The production of polyunsaturated fatty acids (PUFA) by bacteria has been firmly established for over two decades although it is still commonly ignored. Investigations of Antarctic sea ice have revealed a high diversity of novel bacterial taxa with the ability to produce PUFA. The majority are psychrophilic (requiring low temperatures for growth) and halophilic (requiring the presence of salts for growth), in contrast to the bacterial community present in the underlying water column. Specific fatty acids may be used as indicators of PUFA producing bacteria in environmental samples. Structural studies of bacterial phospholipids have been particularly revealing in suggesting biomarkers specific for prokaryotic PUFA input. The use of negative ion fast atom bombardment tandem mass spectrometry for the analysis of bacterial phospholipids has identified species specific for certain groups of bacterial PUFA producers. The phylogeny of PUFA production in the gamma-Proteobacteria also suggests the future use of PUFA genes for the assessment of marine bacterial biodiversity. PMID- 11777567 TI - Ion trap MS(n) for identification of gliotoxin as the cytotoxic factor of a marine strain of Aspergillus fumigatus Fresenius. AB - When cultured in a marine solid medium, a strain of Aspergillus fumigatus (Fresenius) isolated from a shellfish-farming area in the Loire estuary (France) produced a highly cytotoxic exudate. To identify the origin of this activity, a cytotoxicity test on KB cells was used to monitor the purification of the exudate, together with electrospray/ion trap/mass spectrometry (ESI/IT/MS(n)) to detect and identify the toxic compound. After three purification stages, a comparison of fullscan analyses of the last six fractions showed that a monocharged compound at m/z 349 was present only in the active fraction, corresponding to the sodium adduct of gliotoxin [C(13)H(14)N(2)O(4)S(2)+Na](+). Isotopic distribution determination showed that the m/z 349 product possessed two sulphur atoms and multi-stage fragmentation confirmed the hypothesis. MS/MS analysis exhibited the characteristic gliotoxin loss of the disulphide intracyclic bridge. MS(3) analysis revealed four main ions and confirmed the identity of the m/z 349 ion. This study points out that the combined use of a KB cells bioassay and ESI/IT/MS(n) allows a fast and very specific detection and elucidation of unidentified cytotoxic products in natural samples. This method does not require total purification, and it allowed us to report the first detection of gliotoxin production in marine conditions. PMID- 11777568 TI - Combined use of LC/MS and a biological test for rapid identification of marine mycotoxins produced by Trichoderma koningii. AB - Trichoderma koningii Oudemans, a strain isolated from a shellfish farming area, was selected for its high frequency in samples and its ability to produce metabolites when cultured in natural seawater. Combined use of LC/MS and a biological test on blowfly larvae allowed the characterization of four compounds after purification in only two steps (VLC and HPLC). ESI/MS, a powerful tool for rapid identification and sequence determination of peptides, confirmed that these compounds were peptide, alpha-aminoisobutyric acid and amino alcohol (peptaibols), the usual metabolites of Trichoderma. PMID- 11777569 TI - Time-of-flight secondary ion mass spectrometry: characterisation of stainless steel surfaces immersed in natural seawater. AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been employed to study the biofouling of stainless steel samples immersed in seawater. The aim of these characterisations was to understand the initial mechanisms of biomolecule adsorption for relatively short immersion times (from 0 to 24 h). The results show that: (i) there were unavoidable sample "precontaminations" on the surfaces, despite precaution during their preparation and manipulation (washing, drying and storing); (ii) the major peaks detected were the substrate ones whatever the immersion time [However, some organic (nitrogen and oxygen containing) and inorganic secondary ions appeared and grew with the immersion time.]; (iii) the surface contaminations, the nonuniformity of the adsorbed material so as and bacteria have been clearly observed by high-lateral resolution molecular ToF-SIMS mapping. PMID- 11777570 TI - Culture of the marine cyanobacterium, Lyngbya majuscula (Oscillatoriaceae), for bioprocess intensified production of cyclic and linear lipopeptides. AB - Cyanobacteria are an ancient and diverse group of photosynthetic microorganisms, which inhabit many different and extreme environments. This indicates a high degree of biological adaptation, which has enabled these organisms to thrive and compete effectively in nature. The filamentous cyanobacterium, Lyngbya majuscula, produces several promising antifungal and cytotoxic agents, including laxaphycin A and B and curacin A. Samples of L. majuscula collected from Moorea Island, Tahiti (French Polynesia) and from the Culture Collection of Algae and Protozoa (CCAP 1446/4) were studied and adapted to large scale laboratory culture (5 l). This constitutes a 100-fold scale-up for the culture of this particular strain of L. majuscula. The effect of culture vessel configurations, growth conditions and media compositions on growth of L. majuscula was examined. Using optimised culture conditions, two strains of L. majuscula are currently being evaluated for their production of secondary metabolites. Results will be compared with those obtained from four environmental extracts. Comparisons were made by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). It was shown that varying the culture conditions under which L. majuscula was grown had the greatest effect on secondary metabolite production, thus providing potential for future bioprocess intensified production. PMID- 11777571 TI - Novel marine flagellate fatty acid: structural elucidation by GC-MS analysis of DMOX derivatives and DMDS adducts. AB - In situ biodegradation experiments of marine particles were performed in deep Atlantic waters. Lipid changes were associated with the colonization of the decaying detritus by marine flagellates smaller than 10 microm in size. Fatty acid methyl esters (FAMEs) of these flagellates showed high proportion of a FAME with a molecular weight (MW) of 320. Its structure could not be unambiguously resolved by retention times on gas chromatography runs using polar and nonpolar columns, nor by routine gas chromatography coupled to mass spectrometry (GC-MS). Complementary GC-MS analysis of two types of derivatives was performed to fully elucidate the structure of this novel acid. GC-MS analysis of 4,4 dimethyloxazoline (DMOX) derivative of the compound enabled localization of a double bond in position Delta17, whereas other double bond locations could not be unambiguously located by spectrum interpretation. DMDS addition on the flagellate biomarker produced monocyclic triadducts. Fragment suites corresponding to gradual losses of thiomethyl substituents indicated the presence of a five membered thioether cycle, located on the methyl side of the derivative. Fragment suites produced by cleavage of C linked to sulfured substituents revealed various possible structures. However, interpretation of the spectra in relation with the fragmentation of the DMOX derivative yielded a convergent identification of the flagellate biomarker, as a non-methylene-interrupted C20:3Delta7,13,17 FAME. PMID- 11777572 TI - Lipids as indicators of eutrophication in marine coastal sediments. AB - Total organic carbon (TOC) and sedimentary lipid contents were investigated in the Bunnefjord, the most inner part of the Oslofjord (Norway). The Bunnefjord is an intermittent anoxic basin and has undergone major eutrophication since the early 1800s. A core from this fjord was collected at 100 m depths under anoxic remnant waters. The first 15 cm corresponding to deposits from 1500 to present were considered for analysis. Lipid classes were quantified by TLC-FID and the molecular composition of selected lipid classes was investigated by GC and GC-MS. Lipids were dominated by two main classes, phospholipids and hydrocarbons. The hydrocarbons represented up to 7.4% of total lipids in the sediment layers covering the period when the most extensive cultural eutrophication took place (1900 to 1970). The higher fluxes of organic carbon produced during this period may have controlled hydrocarbon inputs into the sediments, due to the hydrophobic character of these pollutants. The hydrocarbon concentration reversed toward pre industrial levels in the more recent layers, which suggests an improvement of the water quality, possibly in response to improved treatment of the sewage in the cities around Bunnefjord. The second most abundant pool of lipids consists in phospholipids, mostly contributed by bacteria. Even though the concentration decreased with depth, their relative proportions to total lipids remained high, mainly in the deepest layers (>80% of total lipids). A rapid decrease of the polyunsaturated fatty acid methyl esters (FAME) from the phospholipid fraction in the upper 4 cm suggests a rapid biodegradation of planktonic inputs and meiofauna. Odd branched fatty acids were more probably contributed by bacteria linked to the high sedimentary hydrocarbon content. The down core distribution of 16:1omega7, 18:1omega7, 18:1omega5 esterified to phospholipids suggests a vertical zonation of the microbial community in relation to redox conditions and available organic matter. In addition to bacterial sulphur biomass, the presence of hopanoic acids in the phospholipids fraction suggests the contribution of bacteria growing on methane. According to the sterol composition, dominated by 4alpha(H)-methylsterols, dinoflagellates represent the major contributors to the organic matter produced in the water column, particularly during the period of extensive eutrophication. Long-chain diols (1,13-C(26), 1,15-C(30) and 1,15 C(32)) and long-chain keto-ols (1,15-C(30) and 1,15-C(32)) are reported for the first time at high latitudes. Their relative distributions (diol and keto-ol indexes of Versteegh et al. [Org. Geochem. 27 (1997)]) have allowed depicting a particular event during the eutrophication period, a freshwater intrusion with inputs of land-derived organic matter. This is in accordance with the downcore distribution of freshwater/terrestrial markers as sitosterol, dehydroabietic acid and iso- and anteiso-pimaric acids. The diol and keto-ol indexes have also underlined the general transition trend from marine to more brackish waters in the Bunnefjord. These last observations provide confidence into the use of these compounds in paleoenvironmental reconstruction. PMID- 11777573 TI - Identification of bacteria from single colonies by fatty acid analysis. AB - While a commercially available system for microbial identification by fatty acid analysis (Microbial Identification System, MIDI, Newark, DE, USA) is available, it requires approximately 40-mg wet weight of biomass. Various authors have published methods for fatty acid analysis of single colonies, but no database of organisms has been developed for those methods. A modification of the MIDI system to increase sensitivity while maintaining relative retention times and peak areas allows the standard peak naming tables and libraries of organisms to be used with single colonies. Samples are evaporated down before injection to concentrate the fatty acids, while splitless injection is used to allow more sample to enter the gas chromatograph. Several known bacteria were correctly identified by this method. PMID- 11777574 TI - Structure of muramic acid TMS derivative mass spectrum's base ion (m/z=185) used for quantification of bacterial peptidoglycan. AB - The use of trimethylsilyl (TMS)-derivatisation for determining muramic acid in environmental and clinical samples by gas chromatography-mass spectrometry provides high detection sensitivity; however, questions have been raised as concerns the chemical structure of the entity giving the strong signal of m/z 185. In the present communication we present evidence that this entity results from the formation of a lactam structure of muramic acid upon derivatisation. PMID- 11777575 TI - Prediction of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus populations in yoghurt by Curie point pyrolysis mass spectrometry. AB - We evaluated the potential of pyrolysis-mass spectrometry (PyMS) for quantifying the binary mixed population of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus in yoghurt. For this purpose, a new analytical approach was developed. The yoghurt was transparised and its total bacterial population was recovered by centrifugation and estimated by turbidimetric measurement. The quantity of each population (L. bulgaricus, S. thermophilus) was then estimated in the pellet by PyMS, and the data were analysed by artificial neural networks (ANNs). In parallel, streptococci and lactobacilli were numerated on SYL agar and these data were used as reference values to predict the bacterial counts of each population by PyMS. A close correlation was established between the streptococci and the lactobacilli counts on SYL agar and PyMS measurements (r(2)=0.98 for S. thermophilus and r(2)=0.96 for L. bulgaricus). Combined turbidimetric measurement and PyMS/ANNs seemed to be a powerful method for obtaining rapid counts of binary mixtures of bacteria in yoghurt. PMID- 11777576 TI - Fly-attracting volatiles produced by Rhodococcus fascians and Mycobacterium aurum isolated from myiatic lesions of sheep. AB - Bacterial strains isolated from the healthy breech mucosa and myiatic wounds of ewes were tested for their volatile production as fly attractants towards Wohlfahrtia magnifica (Diptera: Sarcophagidae). Cultures were studied as fly baits in field experiments, and strains performing with the best chemotropic effect were selected for further analysis. Static and dynamic headspace samples from shaken cultures were examined by gas chromatography-mass spectrometry (GC MS). Strains identified as Rhodococcus fascians and Mycobacterium aurum produced various volatile sulfur compounds and benzene, and proved to be the best fly attractants. PMID- 11777577 TI - Direct interface of chemistry to microbiological systems: membrane inlet mass spectrometry. AB - Direct measurement of dissolved gases and low molecular weight volatiles through permeable membranes (e.g. 50-microm-thick silicone rubber), provides an invaluable tool for the investigation of the activities of microorganisms in the laboratory and in their natural environments. Multiple molecular species are monitored at a single point. Fast response times (t(90%)<1 min) and long-term stability, (<1% week(-1)); high specificity and high sensitivity (e.g. 0.2 microM for O(2), <0.5 mM for ethanol), provides a technique that can provide information on the kinetics of processes over many decades (10(0)-10(6)) of minutes. Spatial resolution of <1 mm enables 3D mapping of gases in complex ecosystems (sediments, peat, soils, biofilms, foodstuffs). Results with membrane inlet mass spectrometry (MIMS) when used in conjunction with confocal scanning laser microscopy, provides a powerful approach to the analysis of kinetic and spatial aspects of natural environments. Examples discussed are peat cores and cheese. PMID- 11777578 TI - Rapid detection of lytic antimicrobial activity against yeast and filamentous fungi. AB - A rapid method for assessing the lytic activity of antimicrobial agents against yeast and fungi has been developed. The assay is based on the release of the intracellular enzyme, maltase (alpha-glucosidase). The released maltase activity was measured colorimetrically by the production of p-nitrophenol from p nitrophenyl-alpha-D-glucopyranoside (PNPG). The lytic activity of different antimicrobial compounds was measured against yeast cells or germinating spores of filamentous fungi. Lytic anti-yeast activity could be detected within 20 min incubation at 30 degrees C against Saccharomyces cerevisiae, Candida albicans, and Cryptococcus neoformans. Lytic anti-fungal activity appeared after 2 h of incubation at 30 degrees C against germinating spores of Aspergillus niger and Botrytis cinerea. Whole cells of either yeast or fungi did not hydrolyze sufficient PNPG within 3 h at 30 degrees C to yield a detectable color change. Lytic activity of enzymes (e.g., Lyticase), antibiotics (e.g., Amphotericin B), and an antibiotic-producing strain of bacteria were detected using the assay. The anti-yeast assay has been adapted to a 96-well microtiter format. Both assays provided a rapid, sensitive, and reproducible detection of lytic anti-yeast and anti-fungal activity. PMID- 11777579 TI - Indirect immunofluorescence colony staining method for detecting bacterial pathogens of tomato. AB - An indirect immunofluorescence colony staining method was developed for the detection of important seed-borne bacterial pathogens of tomato. The method involves the use of specific antiserum for initial binding of target bacteria and visualization of positive colonies with a commercially available secondary antiserum conjugated with FITC and observed under a fluorescence microscope. The indirect method is especially suitable for laboratories, seed companies, and quarantine stations which have no facilities for conjugation of primary antiserum. It is more economical and overcomes the problems generally encountered with variable conjugate quality in new batches of conjugates prepared from the same stock of primary antiserum. The assay is easy to perform and results can be easily assessed by visual scoring or image analyser. Results are available in 4-5 days as compared to 30-45 days in traditional methods. The resulting bacterial culture can be tested by PCR or host infectivity and a culture can be stored for future reference. Used in combination with highly specific antibodies (commercially available monoclonal and recombinant antibodies) it can be used as a very sensitive detection tool and has application potential in localization studies as well. Choosing the right secondary conjugate is however necessary to get best results in the assay. PMID- 11777580 TI - A sandwich-designed temperature-gradient incubator for studies of microbial temperature responses. AB - A temperature-gradient incubator (TGI) is described, which produces a thermal gradient over 34 aluminium modules (15x30x5 cm) intersected by 2-mm layers of partly insulating graphite foil (SigraFlex Universal). The new, sandwich-designed TGI has 30 rows of six replicate sample wells for incubation of 28-ml test tubes. An electric plate heats one end of the TGI, and the other end is cooled by thermoelectric Peltier elements in combination with a liquid cooling system. The TGI is equipped with 24 calibrated Pt-100 temperature sensors and insulated by polyurethane plates. A PC-operated SCADA (Supervisory Control And Data Acquisition) software (Genesis 4.20) is applied for temperature control using three advanced control loops. The precision of the TGI temperature measurements was better than +/-0.12 degrees C, and for a 0-40 degrees C gradient, the temperature at the six replicate sample wells varied less than +/-0.04 degrees C. Temperatures measured in incubated water samples closely matched the TGI temperatures, which showed a linear relationship to the sample row number. During operation for 8 days with a gradient of 0-40 degrees C, the temperature at the cold end was stable within +/-0.02 degrees C, while the temperatures at the middle and the warm end were stable within +/-0.08 degrees C (n=2370). Using the new TGI, it was shown that the fine-scale (1 degrees C) temperature dependence of S(o) oxidation rates in agricultural soil (0-29 degrees C) could be described by the Arrhenius relationship. The apparent activation energy (E(a)) for S(o) oxidation was 79 kJ mol(-1), which corresponded to a temperature coefficient (Q(10)) of 3.1. These data demonstrated that oxidation of S(o) in soil is strongly temperature-dependent. In conclusion, the new TGI allowed a detailed study of microbial temperature responses as it produced a precise, stable, and certifiable temperature gradient by the new and combined use of sandwich-design, thermoelectric cooling, and advanced control loops. The sandwich-design alone reduced the disadvantageous thermal gradient over individual sample wells by 56%. PMID- 11777581 TI - Detection and enumeration of coliforms in drinking water: current methods and emerging approaches. AB - The coliform group has been used extensively as an indicator of water quality and has historically led to the public health protection concept. The aim of this review is to examine methods currently in use or which can be proposed for the monitoring of coliforms in drinking water. Actually, the need for more rapid, sensitive and specific tests is essential in the water industry. Routine and widely accepted techniques are discussed, as are methods which have emerged from recent research developments.Approved traditional methods for coliform detection include the multiple-tube fermentation (MTF) technique and the membrane filter (MF) technique using different specific media and incubation conditions. These methods have limitations, however, such as duration of incubation, antagonistic organism interference, lack of specificity and poor detection of slow-growing or viable but non-culturable (VBNC) microorganisms. Nowadays, the simple and inexpensive membrane filter technique is the most widely used method for routine enumeration of coliforms in drinking water.The detection of coliforms based on specific enzymatic activity has improved the sensitivity of these methods. The enzymes beta-D galactosidase and beta-D glucuronidase are widely used for the detection and enumeration of total coliforms and Escherichia coli, respectively. Many chromogenic and fluorogenic substrates exist for the specific detection of these enzymatic activities, and various commercial tests based on these substrates are available. Numerous comparisons have shown these tests may be a suitable alternative to the classical techniques. They are, however, more expensive, and the incubation time, even though reduced, remains too long for same-day results. More sophisticated analytical tools such as solid phase cytometry can be employed to decrease the time needed for the detection of bacterial enzymatic activities, with a low detection threshold. Detection of coliforms by molecular methods is also proposed, as these methods allow for very specific and rapid detection without the need for a cultivation step. Three molecular-based methods are evaluated here: the immunological, polymerase chain reaction (PCR) and in-situ hybridization (ISH) techniques. In the immunological approach, various antibodies against coliform bacteria have been produced, but the application of this technique often showed low antibody specificity. PCR can be used to detect coliform bacteria by means of signal amplification: DNA sequence coding for the lacZ gene (beta-galactosidase gene) and the uidA gene (beta-D glucuronidase gene) has been used to detect total coliforms and E. coli, respectively. However, quantification with PCR is still lacking in precision and necessitates extensive laboratory work. The FISH technique involves the use of oligonucleotide probes to detect complementary sequences inside specific cells. Oligonucleotide probes designed specifically for regions of the 16S RNA molecules of Enterobacteriaceae can be used for microbiological quality control of drinking water samples. FISH should be an interesting viable alternative to the conventional culture methods for the detection of coliforms in drinking water, as it provides quantitative data in a fairly short period of time (6 to 8 h), but still requires research effort. This review shows that even though many innovative bacterial detection methods have been developed, few have the potential for becoming a standardized method for the detection of coliforms in drinking water samples. PMID- 11777582 TI - Phagocytosis and intracellular killing of Candida albicans blastoconidia by neutrophils and macrophages: a comparison of different microbiological test systems. AB - Polymorphonuclear neutrophils (PMN) and mononuclear phagocytes represent an important first line and effector function in the control of Candida infections. Their relative contribution to host defence is frequently assessed by means of microbiological assays. However, reported results are divergent and might well be associated with study design-related issues. In the present study, we compared frequently used microbiological candidacidal assays, with the purpose of determining the most adequate method for assessment of phagocytosis and intracellular killing. We concluded that microbiological assays using yeast phagocyte suspensions are inappropriate for the assessment of intracellular killing of Candida blastoconidia by murine macrophages, due to adherence or clumping of cells. In contrast, an adherent monolayer of phagocytes can be applied as a single microbiological assay to independently study the process of phagocytosis and intracellular killing, by exudate peritoneal macrophages as well as exudate peritoneal PMN. PMID- 11777583 TI - Time-resolved fluorescence immunoassay (TRFIA) for the detection of Escherichia coli O157:H7 in apple cider. AB - An immunoassay based on immunomagnetic separation and time-resolved fluorometry was developed for the detection of E. coli O157:H7 in apple cider. The time resolved fluorescent immunoassay (TRFIA) uses a polyclonal antibody bound to immunomagnetic beads as the capture antibody and the same antibody labeled with europium as the detection antibody. Cell suspensions of 10(1) to 10(8) E. coli O157:H7 and K-12 organisms per ml were used to test the sensitivity and specificity of the assay. The sensitivity of the assay was 10(3) E. coli O157:H7 cells with no cross-reaction with K-12. Pure cultures of E. coli O157:H7 (10(1) to 10(5) CFU/ml) in apple cider could be detected within 6 h, including 4 h for incubation in modified EC broth with novobiocin and 2 h for the immunoassay. When apple cider was spiked with 1 to 10(3) CFU/ml of E. coli O157:H7 and 10(6) CFU/ml of K-12, our data show that the high level of K-12 in apple cider did not impede the detection of low levels of O157:H7. The minimum detectable numbers of cells present in the initial inoculum were 10(2) and 10(1) CFU/ml after 4- and 6-h enrichment. The TRFIA provides a rapid and sensitive means of detecting E. coli O157:H7 in apple cider. PMID- 11777584 TI - Modified Pseudomonas agar: new differential medium for the detection/enumeration of Pseudomonas aeruginosa in mineral water. AB - Pseudomonas aeruginosa has been implicated as a foodborne and waterborne pathogen and is now considered a primary infectious agent. In the present study, the survival of P. aeruginosa inoculated in mineral water was evaluated by drop counts on Pseudomonas Agar Base (PAB), PAB with CN supplement X107, PAB with cetrimide, PAB with nalidixic acid, and these media with added FeSO(4). Initial counts, before starvation, were the same in all media tested. Following this period, P. aeruginosa became sensitive to PAB with added cetrimide. The addition of FeSO(4) did not improve the recovery of stressed P. aeruginosa but gave colonies a typical dark brown colour being easily differentiated from other species that can grow at 42 degrees C. The modified Pseudomonas agar medium was also tested with several P. aeruginosa strains, other species of Pseudomonas, and other genera. Only P. aeruginosa strains (pyocyanin positive) produced the typical colonies. Our results demonstrate that Pseudomonas agar with ferrous sulphate, used for the differentiation of P. aeruginosa colonies, and nalidixic acid, used as an inhibitor of Gram-positive bacteria, might be a useful medium for the detection of injured P. aeruginosa in mineral water. PMID- 11777586 TI - Cointegrate resolution following transposition of Tn1792 in Streptomyces avermitilis facilitates analysis of transposon-tagged genes. AB - The insertion sequence IS6100, belonging to the IS6 family, normally forms a cointegrate as an end product of transposition. The IS6100-based minitransposon, Tn1792, has been developed as a genetic tool to mutagenise antibiotic-producing Streptomyces. Here, we describe resolution of Tn1792 cointegrates in Streptomyces avermitilis that can facilitate both the initial isolation of Tn1792 insertion mutants and also the subsequent rescue of Tn1792-tagged sequences. This is the first reported example of cointegrate resolution for an IS6-type transposable element. As a result of mutagenesis, several putative genes involved in morphological development and antibiotic production have been isolated. PMID- 11777585 TI - Investigation of lotic microbial aggregates by a combined technique of fluorescent in situ hybridization and lectin-binding-analysis. AB - A technique combining fluorescent in situ hybridization and lectin-binding analysis (FISH-LBA) was developed and applied for the simultaneous detection of cellular components and glycoconjugates in lotic microbial aggregates (river snow). River snow aggregates were directly collected from the bulk water phase into coverslip chambers, in which the complete procedure including fixation, fluorescent in situ hybridization, lectin-binding and optical analysis by confocal laser scanning microscopy was performed. Neither autofluorescence originating from phyotosynthetic organisms nor inorganic particles did negatively interfere with the FISH-LBA technique. In river snow samples obtained from the river Elbe, Germany, distinct compartments of the river snow structure could be visualized with FITC-labelled lectins from Triticum vulgaris, Limulus polyphemus, Arachis hypogaea, Phaseolus vulgaris and Pseudomonas aeruginosa, binding to frequently occurring saccharide residues in the river snow matrix. The analysis could be performed on different levels of complexity. The combined technique visualized bacteria of different phylogenetic groups in the entire river snow structure as well as glycoconjugate components linked with various microcolonies. Different lectins stained slime layers and cell-envelopes of individual eukaryotic and prokaryotic cells. Consequently, application of the FISH-LBA technique allows the linkage between cellular and glycoconjugate identity in complex microbial communities. PMID- 11777587 TI - A one-step method for genetic transformation of non-piliated Neisseria meningitidis. AB - A one-step method to chemically transform non-piliated Neisseria meningitidis strains previously resistant to conventional electrochemical transformation procedures has been developed. This method has been used to generate genetically engineered meningococcal strains disrupted in the structural rmpM gene encoding Rmp. PMID- 11777588 TI - Studies on energetic compounds. 25. An overview of preparation, thermolysis and applications of the salts of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO). AB - The research work reported on the preparation, characterisation and applications of more than 50 salts of NTO has been reviewed thoroughly. A broad classification and sub classification of all these compounds has been given on the basis of nature of the compounds with which NTO forms salts. Attempt has been made to discuss the structure of these salts by summarising analytical data reported from 13C NMR. The structure as determined by IR spectroscopy as well as XRD has also been discussed briefly. A generalised mechanism for the thermolysis of the metal salts has also been given and any deviation from this has been narrated in particular cases. The kinetic details, thermodynamical and thermochemical data as well as performance parameters have also been reviewed. Thus, the futuristic potentials of these salts are analysed critically and further studies have been suggested. PMID- 11777589 TI - Investigation of the stability of a mixture of single-based propellants and resins or polymers. AB - The stabilisation of single-based propellants (SBP) with equal quantities of bisphenol A-based epoxy resin (ER), bromine-containing epoxy resin (BER), chlorinated polyvinylchloride (PCV) and chlorinated rubber (CR) were investigated by viscosimetry and calorimetry. All compounds were thermodynamically compatible with SBP. The degree of stabilisation of SBP was measured after accelerated ageing and was evaluated by the loss of weight and by means of differential scanning calorimetry (DSC). All compounds produced a significant decrease in the loss of weight, typically by more than a factor of 15 compared with unstabilised SBP. The stability of the compounds decreased in the order: CR>BER>PCV>ER. PMID- 11777590 TI - Adsorption of zinc(II) from an aqueous solution onto activated carbon. AB - Adsorption isotherms were measured experimentally for Zn(II) adsorption from aqueous solution onto commercial activated carbons C, F-400, F-300 and Centaur HSL in a batch adsorber. The effects of carbon type and solution pH on adsorption isotherms were evaluated in this work. Nearly three times as much Zn(II) adsorbed onto C carbon as on the other three carbon types. The adsorption isotherm for Zn(II) was dependent on solution pH since Zn(II) did not adsorb to carbon below pH 2, and the adsorption isotherm increased as pH increased from 3 to 7. The adsorption isotherm of Zn(II) on C carbon was temperature independent while on F 400 the isotherm showed unusual behavior as temperature increased. PMID- 11777591 TI - Chromium behavior during thermal treatment of MSW fly ash. AB - Energy-from-waste incineration has been promoted as an environmentally responsible method for handling non-recyclable waste from households. Despite the benefits of energy production, elimination of organic residues and reduction of volume of waste to be landfilled, there is concern about fly ash disposal. Fly ash from an incinerator contains toxic species such as Pb, Zn, Cd and Cr which may leach into soil and ground water if landfilled. Thermal treatment of the fly ash from municipal solid waste has been tested and proposed as a treatment option for removal of metal species such as Pb, Cd and Zn, via thermal re volatilization. However, Cr is an element that remains in the residue of the heat treated fly ash and appears to become more soluble. This Cr solubilization is of concern if it exceeds the regulatory limit for hazardous waste. Hence, this unexpected behavior of Cr was investigated. The initial work involved microscopic characterization of Cr in untreated and thermally-treated MSW fly ash. This was followed by determining leaching characteristics using standard protocol leaching tests and characterization leaching methods (sequential extraction). Finally, a mechanism explaining the increased solubilization was proposed and tested by reactions of synthetic chemicals. PMID- 11777592 TI - Decomposition of aniline in supercritical water. AB - The decomposition of aniline in supercritical water (SCW) was studied. Experiments were performed at various temperatures, pressures, residence times, dosage of oxidant H2O2 and initial aniline concentrations to investigate their effect on the destruction efficiency. Manganous sulfate and ferrous sulfate were screened out during the experiment to study the effect of the homogenous catalysts on destruction efficiency. The effect of pH was also studied. The experiments showed that the dosage of oxidant H2O2, experimental temperature, pressure, reaction residence time and even initial concentration of the aniline in wastewater have a significant affect on the TOC removal; manganous sulfate and ferrous sulfate improve the oxidation; TOC removal improves slightly with a decrease in the initial pH value. At a system temperature 450 degrees C, pressure 28 MPa, initial pH 4.0, residence time 46 s and K value 1.1, TOC removal can reach 100%. PMID- 11777593 TI - The reaction pathway for the heterogeneous photocatalysis of trichloroethylene in gas phase. AB - Trichloroethylene (TCE) has been widely used in industry. It is considered a hazardous and carcinogenic air pollutant. In this investigation, TCE photocatalytic reactions were performed in a packed bed reactor configured as a continuous flow reactor and a FT-IR sample cell used as a batch reactor to determine the intermediates under irradiation by 365 nm UV light. In this study, the intermediates detected during these reactions were phosgene, dichloroacetyl chloride (DCAC), chloroform, hexachloroethane, alcohols, esters, aldehydes, carbon monoxide, and carbon dioxide. The possible reaction mechanisms began with the Cl- subtraction. The Cl radicals then interacted with TCE to form various intermediates and products. PMID- 11777594 TI - Removal of copper from aqueous solution by chitosan in prawn shell: adsorption equilibrium and kinetics. AB - The metal removal capability of prawn shell is evaluated in this study using copper as a model sorbate. A mild deacetylation method was used to convert chitin on the periphery of the shell to chitosan. The equilibrium and kinetic characteristics of copper adsorption on partially deacetylated prawn shell are studied in batch stirred-tank experiments. The extent of copper removal increases with an increase in pH. Both the Langmuir model with pH-dependent parameters and the extended Langmuir-Freundlich model with pH-independent parameters account very well for the measured equilibrium data. Modeling studies using two different second order surface reaction models demonstrate that transient profiles obtained experimentally for a range of initial metal concentrations (C0) and adsorbent dosage are in good agreement with calculated curves of both models. The two rate models can be used for an accurate description of measured kinetic data so long as their rate constants are properly correlated with the two system variables. In contrast, deviation exists between experimental data and theoretical curves calculated from a diffusion-based model. PMID- 11777595 TI - Dechlorination of chlorinated phenols by catalyzed and uncatalyzed Fe(0) and Mg(0) particles. AB - Uncatalyzed, and palladium-catalyzed Fe(0) and Mg(0) systems were examined for their efficiencies of dechlorination of 2.86 mM 4-chlorophenol (4-CP), 2.52 mM 2,6-dichlorophenol (2,6-DCP), 3.03 mM 2,4,6-trichlorophenol (2,4,6-TCP), and 2.48 mM pentachlorophenol (PCP) in 50/50 (v/v) 2-propanol/water under room temperature and pressure conditions. Previous investigators have found that PCP is extremely recalcitrant under these conditions. In this investigation, complete dechlorination of 5.0 ml of 2.48 mM PCP was observed for 1.0 g of 2659 ppm Pd/Mg (20 mesh) after 48 h. The only detectable products were cyclohexanol and cyclohexanone at 25% yield. No other chlorinated or otherwise products were observed by mass spectral analysis. It is hypothesized that volatile low molecular weight species were formed from the Pd/Mg dechlorination of PCP. Under conditions of equal surface area (0.0786 m2), the approximate order of PCP dechlorination power of these systems followed as 2659 ppm Pd/Mg>319 ppm Pd/Mg>Mg approximately 4856 ppm Pd/Fe>Fe. Degradation of the other chlorinated phenols by all metallic systems was more facile than PCP. PMID- 11777597 TI - Risk factors associated with the presence of Sarcocystis neurona sporocysts in opossums (Didelphis virginiana). AB - Sarcocystis neurona is the most important cause of equine protozoal myeloencephalitis (EPM) in horse in the Americas. The only known definitive host for this parasite in the United States is the opossum (Didelphis virginiana); however, despite the importance of the disease, the epidemiology of the parasite in the definitive host is poorly understood. To begin addressing these data gaps, potential risk factors were evaluated for their association with the presence of sporocysts of S. neurona in opossums live-trapped in March 1999 and November 1999 to May 2000. Sporocysts of S. neurona were found in 19 of the 72 animals examined. Potential risk factors evaluated were locality, trap date, age, gender, the presence of young in the pouch of females, and body condition score. Variables that were associated with the presence of S. neurona sporocysts were used in logistic regression analysis. Of the factors examined, season and body condition score were associated with increased odds of an animal harboring sporocysts. PMID- 11777598 TI - Molecular evidence of Babesia caballi (Nuttall and Strickland, 1910) parasite transmission from experimentally-infected SCID mice to the ixodid tick, Haemaphysalis longicornis (Neuman, 1901). AB - Molecular evidence that suggests the possible role of the ixodid tick, Haemaphysalis longicornis and its eggs in the transmission of equine Babesia caballi parasites is presented herein. Using polymerase chain reaction (PCR) to assay for DNA in parasites, presumably acquired by ticks that were allowed to feed on splenectomized-SCID mice, experimentally exposed to in vitro-cultivated B. caballi, we have obtained positive bands that corresponded to the expected B. caballi-specific 430bp gene fragment in 50% of female ticks used, and in 75 and 25% of eggs and larval progeny, respectively. Also, parasite DNA was detected in ticks, eggs and larvae as late as the 16th to the 20th day post-host infestation. Present findings support to the potential role of H. longicornis in the transmission of B. caballi parasites. Its capability, however, to successfully transmit the infection to horses under natural conditions in the field needs to be further ascertained. To our knowledge, this is the first documented study incriminating H. longicornis as a most and likely biological vector of equine babesias. PMID- 11777599 TI - Changes in properties of adenosine transporters in Trypanosoma evansi and modes of selection of resistance to the melaminophenyl arsenical drug, Mel Cy. AB - Resistance to arsenical drugs in trypanosomes has been linked to changes in adenosine uptake. The transport of melaminophenyl arsenicals into Trypanosoma brucei was shown to be mediated by an unusual adenosine nucleoside transporter, P2 (Carter and Fairlamb, 1993), and the loss of this transporter is associated with resistance to melaminophenyl arsenicals in these parasites. To further understand the mechanisms of arsenical resistance, we generated several lines of Mel Cy-resistant T. evansi from a drug-sensitive isolate using both in vivo and in vitro selection methods. Uptake of the melaminophenyl arsenical, Mel Cy on the P2 transporter was studied in the drug-sensitive as well as Mel Cy-resistant parasites, by means of inhibition of Mel Cy-induced lysis of trypanosomes, in an in vitro lysis assay. Adenosine uptake was also investigated using competition inhibition assays. Our study shows that T. evansi, TREU 1840, possesses the P1/P2 adenosine transport system as reported in T. brucei and T. equiperdum. However, in T. evansi, the P2 transporter is the larger transport process instead of the P1. The P2 transporter in T. evansi mediated the uptake of Mel Cy in the drug sensitive parasites. The P2 was retained in all the arsenical-resistant T. evansi lines studied. However, the activity of the transporter was reduced to different extents in the different-resistant lines. The residual P2 activity related well to the levels of drug resistance in each line, suggesting that P2 activity could be an important marker for arsenical resistance. Furthermore, important differences were observed between the in vivo- and the in vitro-selected arsenical-resistant parasites suggesting that there may be differences in resistance phenotypes selected on the field. PMID- 11777600 TI - Trypanosoma evansi experimental infection in the South American coati (Nasua nasua): clinical, parasitological and humoral immune response. AB - The course of Trypanosoma evansi infection in coatis (Carnivora, Procionidae) was followed for 262 days. Parasites were detected in all infected animals from day 2 post infection until the end of the study. No correlation between temperature and parasitemia was observed. Animals of the infected group demonstrated depression, weakness, lethargy and pale mucous membranes. Indirect fluorescent antibody tests detected anti-T. evansi antibodies within 7 to 14 days post infection and showed high levels until the end of the experimental period. The persistent parasitemia in coati and their relative tolerance to clinical signs suggested that this species develops a chronic disease and plays an important role in the epidemiology of trypanosomosis due to T. evansi in enzootic regions. PMID- 11777601 TI - Seroprevalence of Toxoplasma gondii in captive neotropical felids from Brazil. AB - Seroprevalence of Toxoplasma gondii was determined in 865 captive neotropical felids from 20 states from Brazil, sampled from September 1995 to April 1997. Sera were tested by the modified agglutination test (MAT) using formalin-fixed whole tachyzoites and mercaptoethanol. Antibodies (MAT> or =1:20) to T. gondii were found in 472 of 865 (54.6%) cats: in 45 of 99 (45.9%) jaguarundis (Herpailurus yagouaroundi), in 97 of 168 (57.7%) ocelots (Leopardus pardalis), in 68 of 131 (51.9%) oncillas (L. tigrinus), in 35 of 63 (55.5%) margays (L. wiedii), in 1 of 8 (12.5%) Pampas-cat (Oncifelis colocolo), in 9 of 12 (75.0%) Geoffroys-cat (O. geoffroyi), in 134 of 212 (63.2%) jaguars (Panthera onca), and in 83 of 172 (48.2%) pumas (Puma concolor). Antibody titers were: 1:20 in 27 felids, 1:25 in 142 felids, 1:40 in 6 felids, 1:50 in 292 felids, and > or =1:500 in 5 felids. The high seroprevalence of T. gondii antibodies found in the present study suggested a widespread exposure of neotropical cats to T. gondii in zoos in Brazil. The results warrant an investigation on the mode of exposure and oocyst shedding by neotropical cats. PMID- 11777602 TI - The influence of T. evansi infection on the immuno-responsiveness of experimentally infected water buffaloes. AB - In order to define the immuno-suppressive capacity of Trypanosoma evansi infections in buffaloes on the induction of immune responses against heterologous antigens, infected and non-infected buffaloes were vaccinated against Pasteurella multocida (haemorrhagic septicemia) and were simultaneously immunised with a control antigen, human serum albumin (HSA). Antibody responses against HSA were significantly reduced in T. evansi-infected animals, but no conclusive data were obtained on the antibody responses against P. multocida. Conversely, the local inflammatory response at the site of Pasteurella vaccination, as measured by increase in size, was significantly reduced in T. evansi-infected animals. These results indicate that the inductive capacity to mount humoral and cell-mediated immune responses against heterologous antigens is suppressed in T. evansi infected animals. Consequently, T. evansi infection might interfere with the development of protective immunity upon heterologous vaccinations and could explain the poor protection of Pasteurella-vaccinated buffaloes in T. evansi endemic areas of Vietnam. PMID- 11777603 TI - Persistent efficacy of doramectin topical solution against induced infestations of Bovicola bovis and Solenopotes capillatus. AB - A study was conducted in two locations, Wyoming and Wisconsin, USA, to evaluate the persistent efficacy of doramectin topical solution at a dose rate of 500 microg/kg body weight against artificially induced infestations of Bovicola bovis and Solenopotes capillatus on cattle. At each location, lice-free beef calves were individually housed and randomly allocated to treatment. Both B. bovis and S. capillatus were transferred from untreated donor animals to doramectin-treated cattle at the end of 35, 63, 91 or 126 day post-treatment periods. Cattle treated with a saline pour-on served as the control. Based on the geometric means of lice counts 2 weeks following transfer, the persistent efficacy of a single treatment with doramectin topical solution against induced infestations of B. bovis was 100.0, 100.0, 99.5, and 100.0% at post-treatment days of 35, 63, 91, and 126, respectively. Persistent efficacy against induced infestations of S. capillatus, for the same intervals, were 100.0, 94.9, 86.3, and 74.9%. PMID- 11777604 TI - A prevalence survey and risk analysis of filariosis in dogs from the Mt. Vesuvius area of southern Italy. AB - A dog microfilariae prevalence and risk factor survey was conducted in 51 contiguous municipalities of the Mt. Vesuvius area (Campania region, southern Italy) in order to add data to the limited epidemiological information available regarding filarial worms in this zone. Between May 1999 and June 2000, blood samples were collected from 351 asymptomatic dogs. Blood samples were examined using a modified Knott's technique and histochemical staining in order to count and identify microfilariae. The results were subjected to statistical analysis and choroplethic municipal maps (MMs) were drawn by a geographical information system (GIS) software. Microfilariae were detected in 63 of the 351 dogs surveyed, constituting a total filarial prevalence of 17.9%. In particular, 56 dogs (15.9%) showed only microfilariae of Dipetalonema reconditum; three dogs (0.8%) only microfilariae of Dirofilaria repens; two dogs (0.6%) microfilariae of both D. reconditum and D. repens and two dogs (0.6%) microfilariae of both Dirofilaria immitis and D. repens. High D. reconditum prevalence was associated with hunting practice, masculine gender and older dogs. There was also a tendency to find high prevalence in dogs sampled in the afternoon. In conclusion, the presence of microfilariae of D. reconditum in 92% of microfilaraemic dogs indicates that this filarial worm was the predominant filarial species in dogs in the Mt. Vesuvius area. In addition, the general trends of the MMs showed that D. immitis and D. repens were present only in a few municipalities, whereas D. reconditum was widely and homogeneously spread throughout the entire study area. PMID- 11777605 TI - Genetic resistance to gastrointestinal nematode parasites in Rhon sheep following natural infection. AB - Genetic parameters of resistance to gastrointestinal nematodes were estimated in Rhon sheep, a local sheep breed in Germany. In the first year, a total of 131 lambs (born between January and February 1998) from five rams were evaluated. Faecal egg counts (FEC) (n=1528) were measured in all lambs every 2 weeks until 4 months of age and every 4 weeks until 12 months of age in female lambs. In the second year, a total of 129 lambs (born between January and February 1999) from the same rams were evaluated. FEC (n=645) were measured in the lambs every 4 weeks until 5 months of age. Blood was taken in both years at the time of faecal sampling from the jugular vein and haematocrit was measured. Heritabilities for log(10)(FEC+25) were between 0.11 and 0.44. Heritabilities for the corresponding haematocrits were between 0.19 and 0.26 depending on the number of samples taken in account. A significant negative correlation was estimated for the parameters of FEC and daily weight gain (r=-0.57). The results confirm the feasibility of genetic selection in Rhon sheep for resistance to nematode parasites in an environment where Trichostrongylus spp./Teladorsagia spp., Haemonchus contortus and Cooperia spp. are the dominant species. Breeding decisions can be based on one or two samples depending on the mean values and ranges of FEC and haematocrit, respectively. PMID- 11777606 TI - Prevalence and macro- and microscopic lesions produced by Gasterophilus nasalis (Diptera: Oestridae) in the Botucatu Region, SP, Brazil. AB - The objective of the present study was to investigate the prevalence of Gasterophilus nasalis larvae in Botucatu, the central west region of Sao Paulo State, Brazil, and to describe the lesions caused by the parasite. The climate of Botucatu is warm and rainy during the months of December through March and cool and dry during the months of May through August. The prevalence of G. nasalis was 16.84%, and the period of peak infestation corresponded to the months of cold and dry weather. The lesions detected at the sites of larval attachment were examined macro- and microscopically. Erosions and ulcerations of the gastric mucosa and proximal duodenum were the major macroscopic lesions detected. Microscopically, the lesion spectrum ranged from mild inflammatory reactions to extensive necrosis and ulceration. PMID- 11777607 TI - International harmonisation of anthelmintic efficacy guidelines (Part 2). AB - The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities. PMID- 11777608 TI - Development and application of a standardized assay for chemical disinfection of coccidia oocysts. AB - The development and application of a standardized model for testing of anticoccidial disinfectants are described. Due to its economic impact, tenacity of oocysts, and reproducibility of the course of infection Eimeria tenella has been chosen as test organism. Oocysts of the Houghton strain were more susceptible to disinfection with 4% TP4 (Preventol) than oocysts of a field isolate (FI 292/1) as determined by sporulation inhibition and lysis. Scoring of intestinal lesions and of oocyst numbers in mucosal scrapings in chicken infected with various doses of oocysts were found unsuitable for assessment of disinfectants. Because strain differences were observed only Houghton strain oocysts were applied for further testing. Guidelines for standardized in vivo testing of disinfectants have been stipulated by the German Veterinary Society (DVG) on the basis of these studies. When applied for testing of Neopredisan (NP) in two separate laboratories similar results were obtained. Inhibitory activity (IA; proportion of inactivated oocysts) of 92.9 and 90.6% were calculated for 3% NP and of 95.2 and 96.8% for 4% NP after treatment with the disinfectant over 120 min. According to the guidelines IA of at least 95% is required for certification of sufficient disinfecting efficacy by the DVG. PMID- 11777609 TI - Survival of nonsporulated Toxoplasma gondii oocysts under refrigerator conditions. AB - Toxoplasma gondii oocysts are excreted nonsporulated in the feces of the cats into the environment. These oocysts must undergo sporulation to become infectious. Little is known about the factors that influence sporulation of T. gondii oocysts. The present study examined the survival of nonsporulated oocysts under refrigerated conditions over 11-week observation period. Microscopic examination of oocysts indicated that no visible development occurred under refrigerator conditions. The nonsporulated oocysts retained their ability to sporulate when placed at room temperature. The numbers of visually viable appearing oocysts decreased over time. Some oocysts in all samples were infectious for mice despite being refrigerated for up to an 11 weeks before undergoing sporulation. Results indicate that nonsporulated oocysts can survive in the environment for at least 3 months and retain their ability to become infectious when placed under appropriate conditions. PMID- 11777610 TI - Mice lacking the gene for inducible or endothelial nitric oxide are resistant to sporocyst induced Sarcocystis neurona infections. AB - Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. Little is known about the role of immunobiological mediators to this parasite. Nitric oxide (NO) is important in resistance to many intracellular parasites. We, therefore, investigated the role of inducible and endothelial NO in resistance to clinical disease caused by S. neurona in mice. Groups of interferon-gamma gene knockout (IFN-gamma-KO) mice, inducible nitric oxide synthase gene knockout (iNOS-KO) mice, endothelial nitric oxide synthase gene knockout (eNOS-KO) and appropriate genetic background mice (BALB/c or C57BL/6) were orally fed sporocysts or Hanks balanced salt solution. Mice were observed for signs of clinical disease and examined at necropsy. Clinical disease and deaths occurred only in the IFN-gamma-KO mice. Microscopic lesions were seen only in the brains of IFN-gamma-KO mice. Results of this study indicate that iNOS and eNOS are not major mediators of resistance to S. neurona infections. Results of this study suggest that IFN-gamma mediated immunity to S. neurona may be mediated by non-NO-dependent mechanisms. PMID- 11777611 TI - Identification of the Egyptian species of Fasciola. AB - Reports on the species of Fasciola present in the Nile Delta, Egypt, appear controversial. Some authors reported the presence of both Fasciola gigantica and Fasciola hepatica, others reported F. gigantica only and mentioned that F. hepatica was found only in imported animals. This study was an attempt to identify the species of Fasciola flukes collected from locally bred animals. Morphologic, morphoanatomic, morphometric, and chemotaxonomic criteria of the fluke isolates were studied. Speciation based on morphologic and morphometric data was not decisive due to overlap in the values of most measurements. Morphoanatomic data proved the presence of both the species, and isoelectric focusing (IEF) of fluke soluble protein confirmed the presence of both F. gigantica and F. hepatica in Egypt. PMID- 11777612 TI - Control of Echinococcus granulosus in Uruguay: evaluation of different treatment intervals for dogs. AB - This study attempted control of transmission of Echinococcus granulosus from dogs to sheep in different areas in the Department of Florida, Uruguay, by treating dogs with praziquantel at intervals of 6, 12 and 16 weeks. The 6-week interval was based on the prepatent period of infection with E. granulosus, the 12- and 16 week intervals were based on the rate of reinfection with tapeworms in dogs in the area. Dogs had become reinfected with E. granulosus between 2 and 4 months after treatment, whereas they became reinfected with the Taenia spp. tapeworms within 2 months of treatment. One year after the start of treatments sentinel lambs were born and grazed the farms in the three treatment areas. Approximately, 15 months later when the sentinel lambs were killed and examined for parasites the six weekly treatments had stopped the transmission of E. granulosus to the sentinel lambs. Treatment of dogs at 12- and 16-week intervals failed to stop transmission of E. granulosus but both the numbers of farms and the numbers of sheep infected with E. granulosus were lower where dogs received 12 weekly treatments compared with dogs receiving 16 weekly treatments and a fourth area where dogs had received no treatments (chi(2)P=0.002). Lambs continued to become infected with the Taenia spp. tapeworms in all the areas. Control was complicated by large changes in the dog population. From a starting population of 1164 dogs in the three treated areas, 832 new dogs, most of these adult hunting dogs, entered the population and 793 dogs were lost from the population. PMID- 11777613 TI - Feline dirofilariosis: antibody response to antigenic fractions containing specific 20 to 30 kDa polypeptides from the adult Dirofilaria immitis somatic antigen. AB - Fractions from the adult somatic antigen (SA) Dirofilaria immitis complex, containing polypeptides from 20 to 30kDa, previously identified as molecular markers of feline dirofilariosis are isolated by sequential application of gel filtration and anion exchange chromatography. Indirect enzyme-linked immunosorbent assays, employing these fractions (20-26kDa/ELISAF1 and 30kDa/ELISAF7) show multivalent diagnostic capacities: they were able to detect pre-patent infections 2 months after infection, infections in clinical phase, and the fall of antibodies after the worms were removed from the heart, or the application of a ivermectin treatment. The results obtained by the two tests correlated well, in spite of the fact that ELISAF1 was most useful to detect antibodies in sera from cats in the clinical phase, while ELISAF7 has more sensitivity for the early detection of the infections. Both ELISAs were useful in the detection of the decrease of antibodies after the worms were removed by surgery or pharmacological treatment. PMID- 11777614 TI - Variation among Merino sheep in susceptibilty to lice (Bovicola ovis) and association with susceptibility to trichostrongylid gastrointestinal parasites. AB - Sheep of two bloodlines of Merino were artificially infested with equal numbers of lice (Bovicola ovis) and the resulting louse populations were monitored over the following 20 months. The sheep were shorn 6 and 17 months after infestation and, for analysis, the louse counts considered in 3 years separated by shearings. Nematode faecal egg counts (FECs) were assessed on faecal samples collected on five occasions, three times following natural challenge and twice after artificial challenge with 40,000 trichostrongyloid larvae (84% Trichostrongylus vitrinus). In addition, blood samples were collected and measured for B. ovis specific immunoglobulins (predominantly IgG), B. ovis-specific IgE and serum total IgE. Bloodlines differed significantly in the size of louse populations at the end of year 2, FEC after both natural and artificial challenge and in serum levels of all three antibodies (p<0.05). There were also large variations in louse counts and FEC among sheep within bloodlines. Louse counts at inspections after louse populations had been allowed to build up were highly repeatable, both between and within years. However, correlations with counts at inspections soon after initial infestation and following shearing were lower. FEC after natural challenge was correlated with louse counts in year 2 (r=0.45, p<0.01) and year 3 (r=0.38, p<0.05), but the correlation with counts in year 1 was not significant (r=0.25, p>0.05). FEC following artificial challenge was significantly correlated with louse counts in year 3 (r=0.36, p<0.05), but not in year 2 (r=0.25, p>0.05) or year 1 (r=0.04, p>0.05). Louse counts in the 3 years were significantly correlated with anti-B. ovis antibody concentration (r=0.60, 0.48, 0.36), but not with levels of either anti-B. ovis or total serum IgE. These results suggest that sheep with greater resistance to gastrointestinal parasites also tend to be less susceptible to lice. Whether this is due to interaction of the effects of the parasites or to correlation in underlying resistance mechanisms requires clarification. PMID- 11777615 TI - EUD but not QED. PMID- 11777616 TI - The prospects for new treatments for prostate cancer. PMID- 11777617 TI - Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue. AB - PURPOSE: A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low alpha/beta ratio), more typical of the surrounding late-responding normal tissue. METHODS AND MATERIALS: Earlier estimates of alpha/beta for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate specific antigen (PSA), Gleason score, length of follow-up, and age. RESULTS: The estimated value of alpha/beta from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This alpha/beta value is considerably less than typical values for tumors (> or =8 Gy), and more comparable to values in surrounding late-responding normal tissues. CONCLUSIONS: This analysis provides strong supporting evidence that alpha/beta values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced. PMID- 11777618 TI - Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging. AB - PURPOSE: Recently, imaging-based tumor volume before, during, and after radiation therapy (RT) has been shown to predict tumor response in cervical cancer. However, the effectiveness of different methods and timing of imaging-based tumor size assessment have not been investigated. The purpose of this study was to compare the predictive value for treatment outcome derived from simple diameter based ellipsoid tumor volume measurement using orthogonal diameters (with ellipsoid computation) with that derived from more complex contour tracing/region of-interest (ROI) analysis 3D tumor volumetry. METHODS AND MATERIALS: Serial magnetic resonance imaging (MRI) examinations were prospectively performed in 60 patients with advanced cervical cancer (Stages IB2-IVB/recurrent) at the start of RT, during early RT (20-25 Gy), mid-RT (45-50 Gy), and at follow-up (1-2 months after RT completion). ROI-based volumetry was derived by tracing the entire tumor region in each MR slice on the computer work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters (d1, d2, d3) were measured on film hard copies to calculate volume as an ellipsoid (d1 x d2 x d3 x pi/6). Serial tumor volumes and regression rates determined by each method were correlated with local control, disease-free and overall survival, and the results were compared between the two measuring methods. Median post-therapy follow-up was 4.9 years (range, 2.0-8.2 years). RESULTS: The best method and time point of tumor size measurement for the prediction of outcome was the tumor regression rate in the mid-therapy MRI examination (at 45-50 Gy) using 3D ROI volumetry. For the pre-RT measurement both the diameter-based method and ROI volumetry provided similar predictive accuracy, particularly for patients with small (<40 cm3) and large (> or =100 cm3) pre-RT tumor size. However, the pre-RT tumor size measured by either method had much less predictive value for the intermediate-size (40-99 cm3) tumors, which accounted for the majority of patients (55%). Tumor regression rate (fast vs. slow) obtained during mid-RT (45-50 Gy), which could only be appreciated by 3D ROI volumetry, had the best outcome prediction rate for local control (84% vs. 22%, p < 0.0001) and disease-free survival (63% vs. 20%, p = 0.0005). Within the difficult to classify intermediate pre-RT size group, slow ROI-based regression rate predicted all treatment failures (local control rate: 0% vs. 91%, p < 0.0001; disease-free survival: 0% vs. 73%, p < 0.0001). Mid-RT regression rate based on simple diameter measurement did not predict outcome. The early-RT and post-RT measurements were least useful with either measuring method. CONCLUSION: Our preliminary data suggest that for the prediction of treatment outcome in cervical cancer, initial tumor volume can be estimated by simple diameter-based measurement obtained from film hard copies. When initial tumor volume is in the intermediate size range, ROI volumetry and an additional MRI during RT are needed to quantitatively analyze tumor regression rate for the prediction of treatment outcome. PMID- 11777619 TI - Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment. AB - PURPOSE: To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery. METHODS AND MATERIALS: Of 114 patients with cervical cancer Stage IB-IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome. RESULTS: Before treatment, SCC antigen was elevated (>1.9 microg/L) in 60% and CYFRA 21-1 (>2.2 microg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p < 0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p = 0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p = 0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS (p = 0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%. CONCLUSIONS: In patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional salvage surgery. SCC antigen proved to be superior to CYFRA 21-1 in predicting DFS and disease recurrence. PMID- 11777620 TI - The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. AB - PURPOSE: This report presents guidelines for using low-dose-rate (LDR) brachytherapy in the management of patients with cervical cancer. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in LDR brachytherapy for cervical cancer performed a literature review, supplemented by their clinical experience, to formulate guidelines for LDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that radiation treatment for cervical carcinoma (with or without chemotherapy) should include brachytherapy as a component. Precise applicator placement is essential for improved local control and reduced morbidity. The outcome of brachytherapy depends, in part, on the skill of the brachytherapist. Doses given by external beam radiotherapy and brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional practice. The ABS recognizes that intracavitary brachytherapy is the standard technique for brachytherapy for cervical carcinoma. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. The ABS recommends completion of treatment within 8 weeks, when possible. Prolonging total treatment duration can adversely affect local control and survival. Recommendations are made for definitive and postoperative therapy after hysterectomy. Although recognizing that many efficacious LDR dose schedules exist, the ABS presents suggested dose and fractionation schemes for combining external beam radiotherapy with LDR brachytherapy for each stage of disease. The dose prescription point (point A) is defined for intracavitary insertions. Dose rates of 0.50 to 0.65 Gy/h are suggested for intracavitary brachytherapy. Dose rates of 0.50 to 0.70 Gy/h to the periphery of the implant are suggested for interstitial implant. Use of differential source activity or loading minimizes excessive central dose rates. These recommendations are intended only as guidelines. The responsibility for medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are suggested for LDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose reporting policies. PMID- 11777621 TI - Gross tumor volume, critical prognostic factor in patients treated with three dimensional conformal radiation therapy for non-small-cell lung carcinoma. AB - PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) has recently become widely available with applications for patients with non-small-cell lung cancer (NSCLC). These techniques represent a significant advance in the delivery of radiotherapy, including improved ability to delineate target contours, choose beam angles, and determine dose distributions more accurately than were previously available. The purpose of this study is to identify prognostic factors in a population of NSCLC patients treated with definitive 3D-CRT. METHODS AND MATERIALS: Between March 1991 and December 1998, 207 patients with inoperable NSCLC were treated with definitive 3D-CRT. Tumor targets were contoured in multiple sections from a treatment planning computed tomography (CT) scan. Three dimensional treatment volumes and normal structures were reconstructed. Doses to the International Commission on Radiation Units and Measurements (ICRU) reference point ranged from 60 to 83.85 Gy with a median dose of 70 Gy. The median dose inhomogeneity was +/- 5% across planning target volume. Outcome was analyzed by prognostic factors for NSCLC including pretreatment patient and tumor-related factors (age, gender, race, histology, clinical stage, tumor [T] stage, and node [N] stage), parameters from our 3D-CRT system (gross tumor volume [GTV] in cm3), irradiation dose prescribed to isocenter, volume of normal lung exceeding 20 Gy (V20), and treatment with or without chemotherapy. The median follow-up time was 24 months (range, 7.5 months to 7.5 years). RESULTS: One and two-year overall survival rates for the entire group were 59% and 41%, respectively. Overall survival, cause-specific survival, and local tumor control were most highly correlated with the GTV in cm3. On multivariate analysis the independent variable most predictive of survival was the GTV. Traditional staging such as T, N, and overall clinical staging were not independent prognostic factors. Patients receiving ICRU reference doses > or =70 Gy had better local control and cause specific survivals than those treated with lower doses (p = 0.05). Increased irradiation dose did not improve overall survival. CONCLUSIONS: GTV as determined by CT and 3D-CRT planning is highly prognostic for overall and cause-specific survival and local tumor control and may be important in stratification of patients in prospective therapy trials. T, N, and overall stage were not independent prognostic factors in this population of patients treated nonsurgically. The value of dose escalation beyond 70 Gy should be tested prospectively by clinical trial. PMID- 11777622 TI - The time course of radiation therapy-induced reductions in regional perfusion: a prospective study with >5 years of follow-up. AB - PURPOSE: To assess the time-dependence of radiation therapy (RT)-induced reductions in regional lung perfusion, as measured by single photon emission computed tomography (SPECT) lung perfusion scans. METHODS AND MATERIALS: Between 1991 and 1999, 79 patients had SPECT lung perfusion scans before and serially after RT. Changes in regional perfusion were correlated with regional dose using 3D planning tools and image fusion (PLUNC-Plan UNC). Multiple post-RT follow-up scans were evaluated to determine the temporal nature of RT-induced regional perfusion changes. To facilitate the comparison of dose-response curves (DRCs) at different post-RT intervals, each DRC was fit to a linear model and thus described by its slope. RESULTS: There was a dose-dependent reduction in regional perfusion at nearly all time points post-RT (p = 0.0001). The slope of the DRCs for RT-induced reductions in regional perfusion became steeper at essentially each successive follow-up interval (p = 0.0001). However, the increases in slope became progressively smaller at later follow-up intervals. Overall, about 80% of the long-term RT-induced regional perfusion injury was manifest within 12 months post-RT. CONCLUSION: There is a progression of RT-induced reductions in regional perfusion, with most of this injury manifest within 12 months post-RT. Additional regional injury appears to evolve for years. PMID- 11777623 TI - Prophylactic cranial irradiation revisited: cost-effectiveness and quality of life in small-cell lung cancer. AB - PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission. METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis. RESULTS: Among the 98 complete remission patients, the median OS for PCI+ and PCI- patients was 20.0 and 19.0 months, respectively (p > 0.05, nonsignificant). The median disease-free survival was 14.7 and 10.0 months, respectively (p < 0.05). The difference in the mean Q-TWiST survival was significant (p < 0.01). The mean marginal cost was $18,834/PCI+ patient and $17,885/PCI- patient (p > 0.05, nonsignificant). The cost effectiveness ratio was $70/mo of incremental OS if u(tox) and u(rel) (the utility coefficients to reflect the value of time in health states of toxicity and relapse) were assumed to be 1.0. CONCLUSION: PCI is a cost-effective treatment that improves the quality-of-life-adjusted survival for patients with a complete remission of SCLC. PMID- 11777624 TI - Phase I study of weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in Stage III non-small-cell lung cancer. AB - PURPOSE: This is the first report of a Phase I study on concomitant weekly cisplatin and docetaxel chemotherapy with thoracic radiation for Stage III non small-cell lung cancer (NSCLC). The study objectives were to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of docetaxel used in this regimen, and to evaluate the feasibility of weekly concurrent chemoradiotherapy. METHODS AND MATERIALS: Patients with histologically proven and unresectable Stage III NSCLC were the subjects of this study. Cisplatin was administered at a fixed dose of 20 mg/m2, while the dose of docetaxel was increased from 0 to 30 mg/m2 in increments of 10 mg/m2. Chemotherapy was given on the first day of each week for 6 weeks. The primary tumor and regional lymph nodes were irradiated to 54 Gy, followed by an additional 9 Gy boost to the primary tumor, making the total dose 63 Gy at 1.8 Gy/fraction. RESULTS: Sixteen men and 2 women with advanced NSCLC without prior treatment were enrolled. The median age of the group was 58 years (range 49-67). Three patients had Stage IIIa disease and 15 patients had IIIb disease. Dose-limiting Grade 3 esophagitis was encountered at a docetaxel dose level of 30 mg/m2 in 2 of 3 patients. No dose limiting, nonhematologic toxicity occurred in the other patients and no dose limiting hematologic toxicity occurred in any patient. CONCLUSION: The treatment schedule for NSCLC was feasible, with the DLT being esophagitis. We determined the recommended dose of docetaxel to be 20 mg/m2 for a Phase II study when combined with weekly cisplatin and concomitant thoracic RT. PMID- 11777625 TI - Long-term outcome after elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for locally advanced prostate cancer. AB - PURPOSE: To report the 8-year outcome of local dose escalation using high-dose rate conformal brachytherapy combined with elective irradiation of the pelvic lymphatics for localized prostate cancer. METHODS AND MATERIALS: One hundred forty-four consecutively treated men (1986-1992) were recorded prospectively. Twenty-nine (20.14%) patients had T1b-2a tumors, and 115 (79.86%) patients had T2b-3 tumors according to, respectively, American Joint Committee on Cancer/Union Internationale Contre le Cancer 1992. All patients had a negative nodal status, proven by CT or MRI. The mean initial PSA value was 25.61 ng/mL (Initial value for 41.66% of patients was <10 ng/mL, for 21.52% was 10-20 ng/mL, and for 32.63% was >20 ng/mL). The total dose applied by external beam radiotherapy was 50 Gy in the pelvis and 40 Gy in the prostate. The high-dose-rate brachytherapy was delivered in two fractions, which were incorporated into the external beam treatment (after 20-Gy and 40-Gy external beam radiotherapy dose). The dose per fraction was 15 Gy for the PTV1 (peripheral prostate zone) and 9 Gy for the PTV2 (entire prostatic gland). Any patient free of clinical or biochemical evidence of disease was termed bNED. Actuarial rates of outcome were calculated by Kaplan Meier and compared using the log-rank. Cox regression models were used to establish prognostic factors of the various measures of outcome. RESULTS: The median follow-up was 8 years (range 60-171 months). The overall survival rate was 71.5%, and the disease-free survival rate was 82.6%. The bNED survival rate was 72.9%. Freedom from local recurrence for T3 stage was 91.3%, whereas for G3 lesions it was 88.23%. Freedom from distant recurrence for T3 stage was 82.6% and for G3 lesions 70.59%. Univariate survival analyses revealed that low stage (T1 2), low grade (G1-2), no hormonal therapy, initial PSA value less than 40 ng/mL, and PSA normalization <1.0 ng/mL after irradiation were associated with long survival. In multivariate analyses, initial PSA value, PSA kinetics after radiation therapy, and no adjuvant hormonal treatment were independent prognostic factors. Grade 3 late radiation toxicity (according to RTOG/EORTC scoring scheme) was 2.3% for the genitourinary system in terms of cystitis and 4.10% for the gastrointestinal system in terms of proctitis. Grades 4 and 5 genitourinary/gastrointestinal morbidity was not observed. A history of transurethral resection of the prostate with a median interval of less than 6 months from radiotherapy was associated with a high risk of genitourinary toxicity. CONCLUSION: The 8-year results confirm the feasibility and effectiveness of combined elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for cure of localized and especially high-risk prostate cancer. PMID- 11777626 TI - The influence of a rectal balloon tube as internal immobilization device on variations of volumes and dose-volume histograms during treatment course of conformal radiotherapy for prostate cancer. AB - PURPOSE: A prospective comparative study of a subset of 10 consecutive patients was performed, to describe the effects of an air-inflated rectal balloon tube that has been used for prostate immobilization in 360 patients since 1994. In particular, influences on prostate motion, rectum filling variations, and dose volume histograms (DVHs) of the rectum during a course of conformal radiotherapy were investigated. METHODS AND MATERIALS: Computed tomographic (CT) examinations without and with rectal balloon (filled with 40 mL air) were performed at the start (t(0)), middle (t(mi)), and end of treatment (t(e)), resulting in 6 CT scans for each patient. Prostate displacement was measured from a lateral beam's eye-view. DVHs of rectum as a solid organ, and anterior, posterior, and whole rectum wall were calculated at t(0), t(mi), and t(e), and variations during treatment were analyzed for both examinations, with and without balloon. RESULTS: By use of the balloon, rectum filling variations (p = 0.04) and maximum anterior posterior displacements of the prostate (p = 0.008) were reduced significantly, leading to a reduction in DVH variations during treatment. Maximum displacements of posterior prostate border (>5 mm) were found in 8/10 patients without a rectum balloon and in only 2/10 patients with the balloon. The balloon led to a significant reduction in partial posterior rectal wall volumes included in the high-dose regions, without significant changes at the anterior rectum wall in cases of irradiation of the prostate only. However, when entirely irradiating the whole seminal vesicles, this advantage was lost. CONCLUSIONS: The rectal balloon catheter represents a simple technique to immobilize the prostate and to determine the position of the anterior rectal wall at daily treatment. This allows a reduction of margins, because of reduced prostate movement during treatment course. PMID- 11777627 TI - Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma. AB - PURPOSE: To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. METHODS AND MATERIALS: Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: (1) Unit was unavailable (n = 13), (2) Patient was younger than 18 years (n = 17), (3) Patient received accelerated hyperfractionated ERT (n = 6), and (4) Patient refused BRT (n = 2). The median age for whole group was 43 (range: 9-82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2-3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). RESULTS: The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106 patients in Group A and in 2 (5.2%) out of 38 patients in Group B (p > 0.05). Three-year disease-free survival rate was 67% and 80% (p = 0.07), respectively, and 3-year local recurrence-free survival rate was 86% and 94% (p = 0.23) for Group A and B, respectively. Multivariate analysis showed that advanced nodal status and male gender were significantly unfavorable factors for disease-free survival, and Stage II disease was unfavorable for local recurrence-free survival. The administration of adjuvant HDR BRT was not an independent prognostic factor in multivariate analysis. Out of 106 patients, 42 (39.7%) experienced nasal congestion, transient nasal obstruction, and/or fibrinous exudate in response to antihistaminic treatment. Only three (2.8%) patients experienced nasal synechy related, most probably, to the BRT. Five patients developed severe neural complications; only one out of five was observed in Group A. No severe complication attributed directly to BRT was detected. CONCLUSION: The acute and late morbidity of adjuvant HDR BRT is acceptable with our treatment scheme, but we did not find any local control difference between our patients treated with adjuvant BRT after ERT and ERT alone. We believe that the exact role of adjuvant HDR BRT can be elucidated only by prospective randomized studies. PMID- 11777628 TI - Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer. AB - PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy. RESULTS: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors. PMID- 11777629 TI - Irradiation of paranasal sinus tumors, a delineation and dose comparison study. AB - PURPOSE: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas. PATIENTS AND METHODS: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes. These volumes were expanded in three dimensions with a 5-mm margin. At both institutions, a three dimensional conformal treatment plan of 46 Gy to the elective volumes, plus 20 Gy to the boost target volumes, was designed. The delineated volumes and treatment plans were compared. RESULTS: The mean volume ratio between institutions of the elective CTVs was 0.9 (standard error = 0.05). The differences were located mainly at the bottom of the nasal cavity and at the frontal border of the target areas. The differences in boost CTVs were large; the mean volume ratio was 2.6 (standard error = 0.58). After expansion of the CTV, the mean distance between the planning target volume (PTV) and the chiasm differed by 0.5 cm between the two institutions. Cases with smaller distances between the PTV and the chiasm had more underdosage to the PTV. This effect was less pronounced for institution A (1 vol.%/cm) than for institution B (10 vol.%/cm) treatment plans, which were less conformal. When the treatment plan was designed for the PTV of institution B, 23 volume % of the PTV of institution A received <95% of the prescribed dose. If the treatment plan was designed for the (on average larger) PTV of institution A, the underdosed volume of PTV at institution B was 17%. The relative underdosage to the "other" PTV was larger when the original treatment plan was more conformal. CONCLUSION: In the irradiation of paranasal sinus cancer, both the treatment planner and the observer have a significant influence on the dose to the target and organs at risk. Both effects are similar in magnitude. The observer effect increases with more conformal treatment plans. Minimizing the observer variation is important for adequate irradiation of paranasal sinus cancer. PMID- 11777630 TI - Pulmonary toxicity after radiotherapy in primary breast cancer patients: results from a randomized chemotherapy study. AB - PURPOSE: Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC x 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. METHODS AND MATERIALS: Lung function tests (FVC, FEV1, and DL(CO)) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. RESULTS: Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, -6.5%, p = 0.0005; CTCb: -2.0%, p = 0.21; tailored FEC vs. CTCb: -4.5%, p = 0.05). DL(CO) decreased significantly in both groups (tailored FEC: mean difference, -11.2%, p < 0.0001; CTCb: -5.6%, p = 0.02; tailored FEC vs. CTCb: -5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC (p < 0.0001) and by 2.5% in patients treated with CTCb (p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). CONCLUSIONS: Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT). PMID- 11777631 TI - Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. AB - PURPOSE: To assess the incidence of, and clinical factors associated with, symptomatic radiation pneumonitis (RP) after tangential breast/chest wall irradiation with or without regional lymph node treatment. METHODS AND MATERIALS: The records of 613 patients irradiated with tangential photon fields for breast cancer with >6 months follow-up were reviewed. Clinically significant RP was defined as the presence of new pulmonary symptoms requiring steroids. Data on clinical factors previously reported to be associated with RP were collected, e.g., tamoxifen or chemotherapy exposure and age. The central lung distance (CLD) and the average of the superior and inferior mid lung distance (ALD) in the lateral tangential field were measured on simulator films as a surrogate for irradiated lung volume. Many patients were treated with partly wide tangential fields that included a heart block shielding a part of the lower lung. RESULTS: RP developed in 15/613 (2.4%) patients. In the univariate analysis, there was an increased incidence of RP among patients treated with local-regional radiotherapy (RT) (4.1%) vs. those receiving local RT only (0.9%) (p = 0.02), and among patients receiving chemotherapy (3.9%) vs. those not treated with chemotherapy (1.4%) (p = 0.06). According to multivariate analysis, only the use of nodal RT remained independently associated with RP (p = 0.03). There was no statistically significant association between ranked CLD or ALD measurements and RP among patients treated with nodal irradiation with tangential beams. However, there was a statistically nonsignificant trend for increasing rates of RP with grouped ALD values: below 2 cm (4% RP rate), between 2 and 3 cm (6%), and above 3 cm (14%). CONCLUSIONS: RP was an uncommon complication, both with local and local-regional RT. The addition of regional lymph node irradiation slightly increased the incidence of RP among patients treated with the partly wide tangential field technique. Concern for RP should, however, not deter patients with node-positive breast cancer from receiving local-regional RT. PMID- 11777632 TI - Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients. AB - PURPOSE: Although the role of radiotherapy (RT) after mastectomy in reducing the local relapse rate is well established, its impact on overall survival is strongly questioned. Up to 70% of patients will not benefit from additional RT, and a "wait and see" policy is often adopted. Establishment of short, still safe, and effective RT regimens would render adjunctive radiotherapy more appealing. We evaluated the toxicity and efficacy of a Hypofractionated and intensively Accelerated RT regimen supported with amifostine Cytoprotection (HypoARC) in a cohort of 72 high-risk breast cancer patients treated with modified mastectomy or conservative surgery and FEC (5-fluorouracil/epirubicin/cyclophosphamide) chemotherapy. PATIENTS AND METHODS: A high dose of amifostine, 1,000 mg, was given as a 5-min i.v. infusion before each of the 12 consecutive fractions of RT (4 x 3.5 Gy/fraction and 8 x 4 Gy/fraction, 1 fraction/day, 5 fractions/week). The breast or chest wall, as well as supraclavicular and axillary area, was included in the RT fields. The follow-up of patients ranged from 18 to 42 months (median, 28 months). Alkaline phosphatase (AF) expression was assessed immunohistochemically in normal and cancerous breast tissues. RESULTS: Ninety-two percent of patients successfully completed the regimen, the only side effects being mild nausea and asthenia. In 7% of patients, amifostine was interrupted because of a rash/fever reaction. A dramatic reduction in acute skin toxicity was noted (p < 0.0001). Acute pneumonitis, as well as late toxicity in breast, chest wall, axillary, and lung tissue, was lower with the HypoARC regimen, although not significantly, than with the standard fractionation regimen used to treat two matched control cohorts. Both HypoARC and standard RT significantly reduce the local relapse rate (p < 0.0001), although the local relapse-free and overall survival times were marginally better for the HypoARC group of patients (p > 0.09). AF showed a mixed nuclear/cytoplasmic pattern of expression in the epithelial, endothelial, and stromal component of the normal breast and benign lesions, whereas an impressive loss of AF expression was noted in in situ and invasive breast cancer and tumoral stroma. CONCLUSIONS: The HypoARC regimen is convenient for both patients and radiotherapy departments. The regimen is well tolerated and shows a significantly better profile in terms of early toxicity; a reduced rate of late sequel may be expected. The local relapse rate is as low as that expected from conventional RT. The absence of AF expression in cancer cells and tumoral stroma is probably a major reason for the selective protection of normal breast tissue by amifostine. PMID- 11777633 TI - Preliminary results for prone-position breast irradiation. AB - PURPOSE: To evaluate an alternative prone-position technique for breast irradiation after conservative surgery. METHODS AND MATERIALS: A plexiglas platform with a circular opening for the breast and a double 30 degrees craniocaudal and 10 degrees transverse (left-right for the right breast and right left for the left breast) slope was evaluated for positioning, the possible use of CT, and dosimetric study in 35 patients with large pendulous breasts who were likely to benefit from irradiation of the breast alone after conservative surgery. RESULTS: The positioning was excellent for all but 3 obese patients who could not achieve adequate prolonged immobilization. The platform height and position made it possible to obtain CT in the other 32 patients. Three dimensional dosimetry revealed that 85 degrees and 265 degrees angles of the tangential fields for the right breast and 275 degrees and 95 degrees angles for the left breast were adequate for all patients. The use of 4 or 6 MV photon energy and a variety of wedges made it possible to treat the whole breast and the chest wall. The high-dose regions of the base and the top of the breast did not exceed 105%. No interruption was necessary during treatment, and only grade I-II acute skin reactions were observed. CONCLUSION: The results of this study have demonstrated the feasibility of the technique, which has the great advantage of using a similar position for CT scanning and treatment. PMID- 11777634 TI - Subdiaphragmatic Hodgkin's disease: the University of Florida experience. AB - PURPOSE: To assess the long-term outcomes and late effects of patients with subdiaphragmatic Hodgkin's disease. METHODS AND MATERIALS: Twenty-one patients with Stage I and II subdiaphragmatic Hodgkin's disease were treated with curative intent between February 1966 and February 1998 at the University of Florida. Patient characteristics were as follows: mean age, 38.7 years (range, 3-75 years); 20 males and 1 female; 33% lymphocyte predominant, 43% nodular sclerosing, 14% mixed cellularity, 5% lymphocyte depletion, and 5% unclassified Hodgkin's disease. Treatment included inverted Y irradiation (InY) (8 patients), total nodal irradiation (TNI) (7 patients), and combined modality irradiation and chemotherapy (CMT) (6 patients). Median follow-up was 12.3 years (range, 3.1-33.6 years). RESULTS: Progression-free survival and overall survival were 80% and 70%, respectively, at 10 years. There were no deaths from Hodgkin's disease. Treatment failures occurred in 1 of 8 patients after InY, 1 of 7 after TNI, and 1 of 6 after CMT. Two of 3 recurrences were in patients with 3 or more sites of involvement and/or splenic involvement; 1 was in-field. There were 5 second malignant neoplasms and 3 cardiac events, including 4 second malignant neoplasms and 2 cardiac events in the 9 patients > or =40 years old at diagnosis and 1 second malignant neoplasm and 1 cardiac event in the 12 patients <40 years old. All 3 second solid malignancies in this study occurred 7-14 years after treatment in areas receiving 10-20 Gy. CONCLUSIONS: Subdiaphragmatic Hodgkin's disease is an uncommon manifestation with excellent disease control achieved with InY, TNI, and CMT. This subgroup of patients with Hodgkin's disease is predominantly male and older than subgroups with other presentations, which may predispose the group to a higher risk for serious adverse events after treatment. We recommend InY with spleen for clinical Stages IA and nodular sclerosis or lymphocyte predominant clinical Stage IIA, InY alone for pathologic Stages IA and IIA, and CMT for all Stage I/II patients with greater than three involved sites, B symptoms, bulky disease (>6 cm), central (para-aortic) presentation, or splenic involvement. PMID- 11777635 TI - Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. AB - PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5 fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5 fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease. PMID- 11777636 TI - The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU based chemotherapy and radiation therapy for rectal cancer. AB - PURPOSE: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5 fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment planning tools to more precisely quantify this dose-volume relationship. METHODS AND MATERIALS: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. RESULTS: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V15) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. CONCLUSIONS: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy for rectal carcinoma. PMID- 11777637 TI - Targeting the adventitia with intracoronary beta-radiation: comparison of two dose prescriptions and the role of centering coronary arteries. AB - PURPOSE: To compare by intravascular ultrasound (IVUS) the efficacy of delivering the prescribed dose to the adventitia between two commonly used dose prescriptions for intracoronary radiotherapy. METHODS AND MATERIALS: In 59 human postangioplasty coronary vessels, one IVUS cross-section (1 mm thick) with the highest plaque burden was used for creating dose-volume histograms with different hypothetical positions of the source. RESULTS: On average, prescription to 1 mm beyond lumen surface resulted in delivery of the prescribed dose (20 Gy +/- 20%) to a higher fraction of adventitial volume than with the prescription to 2 mm from the source, with source placed in vessel center, lumen center, or in the IVUS catheter position. Source placement in the lumen center resulted in a low dose heterogeneity to the adventitia and the least dose heterogeneity to the intima. CONCLUSIONS: Prescription to 1 mm beyond lumen surface appeared more effective in delivering the prescribed dose to the adventitia than the American Association of Physicists in Medicine (AAPM) recommended prescription to 2 mm from the source center. Moreover, centering the source in the lumen provides the better balance of effective adventitial targeting and intimal dose homogeneity. Modification of the current AAPM recommendation for dose prescription for intracoronary radiotherapy should be considered. PMID- 11777638 TI - A long-term follow-up study after retro-orbital irradiation for Graves' ophthalmopathy. AB - PURPOSE: The aim of this retrospective analysis was to find out whether low-dose radiation, which is used in the treatment of Graves' ophthalmopathy, could cause radiation-induced cancer, which would in turn adversely affect the survival of the irradiated population and cause an increase in the cancer-specific death rate. METHODS AND MATERIALS: From 1963 to 1978, 250 patients received bilateral orbital irradiation for a progressive Graves' ophthalmopathy. Median age was 49 years. Overall survival and causes of death were evaluated with the help of patients still living, registration offices, medical records, referring physicians, and relatives. Survival curves were calculated with the Kaplan-Meier method. The outcome for each patient was compared with data from life tables regarding gender, age, and calendar period-specific person-years at risk. In addition, treatment outcome for living patients was evaluated with a questionnaire. RESULTS: After a median follow-up of 31 years, 102 patients are still alive, 123 patients have died, and 25 patients have been lost to follow-up. The 10-year, 20-year, and 30-year survival rates were 89%, 68%, and 49%, compared with the age-adapted survival rate of the normal population of 92%, 76%, and 52%. Evaluation of cancer-specific survival was possible in 166 cases. The 10-year, 20 year, and 30-year cancer-specific survival rates were 98%, 92%, and 88%, compared with 97%, 93%, and 87% in the normal population. Treatment response was evaluable in 94 cases. A complete response was reported in 41 patients, a partial response in 39 patients, and no change in 14 patients. CONCLUSIONS: No significant evidence of radiation-induced cancer death was seen in this small cohort of patients treated with radiotherapy for Graves' ophthalmopathy. The long-term treatment results seem to be satisfactory. Studies with greater numbers of patients are necessary to examine the risks and benefits more precisely. PMID- 11777639 TI - Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy. AB - BACKGROUND: The large patient-to-patient variability in the grade of normal tissue injury after a standard course of radiotherapy is well established clinically. A better understanding of this individual variation may provide valuable insights into the pathogenesis of radiation damage and the prospects of predicting the outcome. PURPOSE: To estimate the relative importance of the stochastic vs. patient-related components of variability in the expression of radiation-induced normal tissue damage. METHODS AND MATERIALS: The study data were selected from the dose fractionation studies of Turesson in Gothenburg. Patients treated with bilateral internal mammary fields, who completed at least 10 years of follow-up, were included. The material included 22 different fractionation schedules (11 on each side). Telangiectasia was graded on an arbitrary 6-point scale using clinical photographs of the irradiated fields. For each field, in each patient, a curve showing the grade of telangiectasia as a function of time was constructed. A measure of radioresponsiveness was obtained from the difference between the area under the curve (AUC) for a specific field in an individual patient minus the mean AUC of fields receiving the same dose fractionation schedule. As a confirmatory procedure, the same analysis was repeated with a weighted area under the curve (WAUC) approach, in which the time spent at or above each of the 5 nonzero grades was calculated for each field in each patient. These times were used as explanatory variables in a linear regression analysis of biological equivalent dose to establish statistically the weight of each grade providing the optimal relationship between dose and effect. Using these regression coefficients, the weighted area under the grade-time curve (WAUC) was estimated. RESULTS: The AUC was significantly correlated with the isoeffective dose in 2-Gy fractions (ID2). An analysis of variance components, using the maximum likelihood method, showed that 90% (with 95% confidence limits 65% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Through the linear regression analysis between the AUC and the ID2, it was estimated that patients with a reaction that is 1 SD from the population mean would require a dose modification of approximately 23 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average. Similarly, the WAUC was significantly correlated with the ID2, and 81% (with 95% confidence limits 49% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Patients with a reaction that is 1 SD from the population mean would require a dose modification of approximately 21 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average. CONCLUSION: For a given fractionation schedule, patient-related factors explain 81-90% of the patient-to-patient variation in telangiectasia level seen after radiotherapy. The remaining 10-19% are explained by stochastic effects. This observation encourages further research into genetic or phenotypic assays of normal tissue radioresponsiveness. PMID- 11777640 TI - Dose-volume effects in the rat cervical spinal cord after proton irradiation. AB - PURPOSE: To estimate dose-volume effects in the rat cervical spinal cord with protons. METHODS AND MATERIALS: Wistar rats were irradiated on the cervical spinal cord with a single fraction of unmodulated protons (150-190 MeV) using the shoot through method, which employs the plateau of the depth-dose profile rather than the Bragg peak. Four different lengths of the spinal cord (2, 4, 8, and 20 mm) were irradiated with variable doses. The endpoint for estimating dose-volume effects was paralysis of fore or hind limbs. RESULTS: The results obtained with a high-precision proton beam showed a marginal increase of ED50 when decreasing the irradiated cord length from 20 mm (ED50 = 20.4 Gy) to 8 mm (ED50 = 24.9 Gy), but a steep increase in ED50 when further decreasing the length to 4 mm (ED50 = 53.7 Gy) and 2 mm (ED50 = 87.8 Gy). These results generally confirm data obtained previously in a limited series with 4-6-MV photons, and for the first time it was possible to construct complete dose-response curves down to lengths of 2 mm. At higher ED50 values and shorter lengths irradiated, the latent period to paralysis decreased from 125 to 60 days. CONCLUSIONS: Irradiation of variable lengths of rat cervical spinal cord with protons showed steeply increasing ED50 values for lengths of less than 8 mm. These results suggest the presence of a critical migration distance of 2-3 mm for cells involved in regeneration processes. PMID- 11777641 TI - Prevention of radiation-induced mammary tumors. AB - The radiation-induced rat mammary tumor model is useful for studying tumor prevention by treatment in the initiation or promotion stage. In anti-initiation experiments, the administration of radical scavengers or spin-trapping agents before or immediately after irradiation reduced the incidence of mammary tumors, suggesting that free radicals produced by exposure are a potent initiator. To evaluate the role of nitric oxide (NO) in the initiation, NO-specific scavengers or NO synthase inhibitors were administered during the initiation. These agents partially prevented the tumorigenesis, suggesting that radiation-induced NO contributes to tumor initiation. The administration of curcumin during irradiation reduced the incidence of the tumors in the presence of tumor promotor. In anti-promotion experiments on preventing diethylstilbestrol (DES) dependent tumor development from mammary primodial cells exposed to radiation, tamoxifen decreased the tumor incidence. From the results, estrogen itself or prolactin induced by estrogen may be a promoter for the tumorigenesis. Bezafibrate and simvastatin, agents inducing hypolipidemia and hypocholesterolemia respectively, cause a decrease in the DES-dependent promotion of radiation-induced tumorigenesis. The simultaneous administration of curcumin and DES significantly reduces the development of mammary tumors in irradiated rats. In this review, the endocrinologic and pharmacologic significance of the anti-initiation and anti-promotion is discussed. PMID- 11777642 TI - Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose. AB - PURPOSE: The equivalent uniform dose (EUD) for tumors is defined as the biologically equivalent dose that, if given uniformly, will lead to the same cell kill in the tumor volume as the actual nonuniform dose distribution. Recently, a new formulation of EUD was introduced that applies to normal tissues as well. EUD can be a useful end point in evaluating treatment plans with nonuniform dose distributions for three-dimensional conformal radiotherapy and intensity modulated radiotherapy. In this study, we introduce an objective function based on the EUD and investigate the feasibility and usefulness of using it for intensity-modulated radiotherapy optimization. METHODS AND MATERIALS: We applied the EUD-based optimization to obtain intensity-modulated radiotherapy plans for prostate and head-and-neck cancer patients and compared them with the corresponding plans optimized with dose-volume-based criteria. RESULTS: We found that, for the same or better target coverage, EUD-based optimization is capable of improving the sparing of critical structures beyond the specified requirements. We also found that, in the absence of constraints on the maximal target dose, the target dose distributions are more inhomogeneous, with significant hot spots within the target volume. This is an obvious consequence of unrestricted maximization target cell kill and, although this may be considered beneficial for some cases, it is generally not desirable. To minimize the magnitude of hot spots, we applied dose inhomogeneity constraints to the target by treating it as a "virtual" normal structure as well. This led to much-improved target dose homogeneity, with a small, but expected, degradation in normal structure sparing. We also found that, in principle, the dose-volume objective function may be able to arrive at similar optimum dose distributions by using multiple dose-volume constraints for each anatomic structure and with considerably greater trial-and-error to adjust a large number of objective function parameters. CONCLUSION: The general inference drawn from our investigation is that the EUD-based objective function has the advantages that it needs only a small number of parameters and allows exploration of a much larger universe of solutions, making it easier for the optimization system to balance competing requirements in search of a better solution. PMID- 11777643 TI - Investigation of the added value of high-energy electrons in intensity-modulated radiotherapy: four clinical cases. AB - PURPOSE: Intensity-modulated radiotherapy (IMRT) with photon beams is currently pursued in many clinics. Theoretically, inclusion of intensity- and energy modulated high-energy electron beams (15-50 MeV) offers additional possibilities to improve radiotherapy treatments of deep-seated tumors. In this study the added value of high-energy electron beams in IMRT treatments was investigated. METHODS AND MATERIALS: In a comparative treatment planning study, conventional treatment plans and various types of IMRT plans were constructed for four clinical cases (cancer of the bladder, pancreas, chordoma of the sacrum, and breast). The conventional plans were used for the actual treatment of the patients. The IMRT plans were optimized using the Orbit optimization code (Lof et al., 2000) with a radiobiologic objective function. The IMRT plans were either photon or combined electron and photon beam plans, with or without dose homogeneity constraints assuming standard or increased radiosensitivities of organs at risk. RESULTS: Large improvements in expected treatment outcome are found using IMRT plans compared to conventional plans, but differences in tumor control probability (TCP) and normal tissue complication probabilities (NTCP) values between IMRT plans with and without electrons are small. However, the use of electrons improves the dose-volume histograms for organs at risk, especially at lower dose levels (e.g., 0-40 Gy). CONCLUSIONS: This preliminary study indicates that addition of higher energy electrons to IMRT can only marginally improve treatment outcome for the selected cases. The dose-volume histograms of organs at risk show improvements for IMRT with higher energy electrons, which may reduce tumor induction but does not substantially reduce NTCP. PMID- 11777644 TI - Reduction of rectal dose by integration of the boost in the large-field treatment plan for prostate irradiation. AB - PURPOSE: To reduce the dose in the rectal wall from prostate irradiation at high dose levels. METHODS AND MATERIALS: Treatment plans in which the boost fields were integrated into the large fields (simultaneous integrated boost [SIB]) were compared with plans in which the large fields and boost fields were planned individually and applied in a sequential manner (sequential boost). Two target volumes were delineated: PTV1, the target volume of the large fields that is irradiated to 68 Gy, and PTV2, the target volume of the boost fields that is irradiated to 10 Gy. The sequential boost and the SIB were normalized to the mean dose in PTV2, being 78 Gy. We used a five-field intensity-modulated radiotherapy (IMRT) technique, applied in a step and shoot mode, and included beam weight optimization. A set of 5 patients with varying degree of overlap between PTV1 and the rectal wall was used for analysis. RESULTS: The SIB resulted in a reduction of the dose in the rectal wall. Rectal normal tissue complication probability (NTCP) decreased for the SIB, on average, by a factor of almost 2, compared with the sequential boost. CONCLUSION: The SIB reduced the dose in the rectal wall, compared with the sequential boost technique. PMID- 11777645 TI - Daily targeting of intrahepatic tumors for radiotherapy. AB - INTRODUCTION: A system has been developed for daily targeting of intrahepatic tumors using a combination of ventilatory immobilization, in-room diagnostic imaging, and on-line setup adjustment. By reducing geometric position uncertainty, as well as organ movement, this system permits reduction of margins and thus potentially higher treatment doses. This paper reports our initial experience treating 8 patients with focal liver tumors using this system. METHODS AND MATERIALS: The system includes diagnostic X-ray tubes mounted on the wall and ceiling of a treatment room, an active matrix flat panel imager, in-room control for image acquisition and setup adjustment, and a ventilatory immobilization system via active breathing control (ABC). Eight patients participated in the study, two using an early prototype ABC unit, and the remaining six with a commercial ABC system and improved setup measurement tools. Treatment margins were reduced, and dose consequently increased because of increased confidence in target position under this protocol. After daily setup via skin marks, orthogonal radiographs were acquired at suspended ventilation. The images were aligned to the CT model using the diaphragm for inferior-superior (IS) alignment, and the skeleton for left-right (LR) and anterior-posterior (AP) alignment. Adjustments were made for positioning errors greater than a threshold (3 or 5 mm). After treatment, retrospective analysis determined the final setup accuracy, as well as the error in initial setup measurement performed before setup adjustment. RESULTS: Two hundred sixty-two treatment fractions were delivered on eight patients, with 171 treatments requiring repositioning. Typical treatment times were 25-30 min. Patients were able to tolerate ABC throughout the course of treatment. Breath holds up to 35 s long were used for treatment. The use of on line imaging and setup adjustment reduced setup errors (sigma) from 4.0 mm (LR), 6.7 mm (IS), and 3.8 mm (AP) to 2.1 mm (LR), 3.5 mm (IS), and 2.3 mm (AP). Prescribed doses were increased using this system by an average of 5 Gy. CONCLUSIONS: Daily targeting of intrahepatic targets has been demonstrated to be feasible. The potential for reduction in treatment margin and consequential safe dose escalation has been demonstrated, while maintaining reasonable treatment delivery times. PMID- 11777647 TI - In regard to Gaffney et al., IJROBP 2001;49:539-546. PMID- 11777648 TI - Of scientific physicians and evidence-based medicine. PMID- 11777651 TI - In regard to "research in medical physics," IJROBP 49:891-895; 2001. PMID- 11777654 TI - MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) conference. Hamburg, Germany, 10 May 2001. PMID- 11777655 TI - Determining the value of antimicrobial surveillance programs. AB - Antimicrobial surveillance programs provide important information on the development of bacterial resistance mechanisms in different geographical regions. Data concerning these mechanisms and patterns of antimicrobial resistance allows the implementation of changes in antimicrobial prescribing practices and infection control interventions. The three most widely known global surveillance programs currently in active operation are: The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC), The SENTRY Antimicrobial Surveillance Program, and The Alexander Project. This presentation reviews these surveillance programs, using a set of key criteria in order to assess the significance of each program in monitoring the spread of antimicrobial resistance. The content of the MYSTIC Program monitors the in vitro performance of meropenem in hospital units in which this drug is actively prescribed. This distinguishes the MYSTIC Program from the other two major surveillance programs as it seeks to correlate antimicrobial resistance data, collected from high carbapenem usage institutions, with antimicrobial prescribing patterns over time. The MYSTIC Program and other assessed networks appear to be both valuable and complementary in their design and function. PMID- 11777656 TI - Antimicrobial resistance trends in medical centers using carbapenems: report of 1999 and 2000 results from the MYSTIC program (USA). AB - Trends in susceptibility to antimicrobials were assessed from United States participants using 4488 isolates in the MYSTIC Program, 1999 (10 centers) through 2000 (15 centers). Diverse types of hospitals (general service, university, cancer, federal, pediatric, cystic fibrosis) were enrolled from 13 states. In 2000, oxacillin-susceptible staphylococci were 100% susceptible to meropenem, imipenem, and cefepime; but only 88% of strains were susceptible to ceftazidime. Among Enterobacteriaceae, > or = 96% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem, imipenem, and cefepime; but ceftazidime, ceftriaxone, and piperacillin/tazobactam had 5-20% resistance rates. Extended-spectrum beta-lactamase resistance rates in Klebsiella spp. and Escherichia coli (6-7% and 3-5%, respectively) were stable over 2 years. Acinetobacter spp. were 78-81% susceptible to carbapenems but only 63-72% susceptible to ciprofloxacin. Meropenem, tobramycin, and piperacillin/tazobactam were the most active against Pseudomonas aeruginosa, but ciprofloxacin inhibited only 74% in 2000. Overall, meropenem remained the most potent agent, especially against ceftazidime- or piperacillin/tazobactam-resistant strains. PMID- 11777657 TI - MYSTIC program: summary of European data from 1997 to 2000. AB - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study providing in-vitro surveillance data on microbial susceptibility in centers that prescribe meropenem. This paper summarizes data on the activity of meropenem and five comparator agents against 13,793 clinical isolates from 31 centers in 10 European countries, 1997-2000. Meropenem and imipenem demonstrated broad-spectrum activity against the tested organisms, including beta-lactamase-producing strains that were co-resistant to quinolones and aminoglycosides. The carbapenems were active against the most frequently isolated pathogens including staphylococci (98-100% susceptible), Pseudomonas aeruginosa (65-82% susceptible) and Klebsiella pneumoniae (98-100% susceptible). Resistance to penicillins and cephalosporins was observed, particularly among Enterobacter species in Southern and Eastern Europe. Eastern Europe showed a high prevalence of AmpC beta-lactamase and extended-spectrum beta-lactamase-producing strains in Russia (2000); 47% and 28% of Enterobacteriaceae isolates were AmpC or ESBL-producers, respectively. There was no significant decrease in susceptibility to the carbapenems throughout the four-year period. Meropenem and imipenem appear to remain reliable options for the treatment of serious nosocomial infections. PMID- 11777658 TI - Unit differences in pathogen occurrence arising from the MYSTIC program European database (1997-2000). AB - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997-2000) showed that the most prevalent isolates tested overall were methicillin susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum beta-lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained > 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens. PMID- 11777660 TI - Assessment of a new test to detect Legionella urinary antigen for the diagnosis of Legionnaires' Disease. AB - Given that the rate of mortality by Legionella pneumonia increases in incorrectly treated patients, rapid diagnosis and early antibiotic treatment are needed. We have assessed the performance of a new enzyme immunoassay (EIA) test (Bartels Inc. Trinity Biotech Company, Wicklow, Ireland) to detect Legionella pneumophila antigen in urine comparing it to Binax EIA (Binax, Portland, Maine). We also evaluated the capability of both EIAs to detect extracted soluble antigens of Legionella strains. Using nonconcentrated urine samples (NCU) the sensitivity of Bartels EIA was 74.1% (66/89) and the sensitivity of Binax EIA was 51.7% (46/89). The sensitivity of both EIA tests were 91.5% (54/59) using concentrated urine samples (CU). Specificity of both EIA tests was 100% in NCU and CU. Bartels EIA was able to detect all serogroup L. pneumophila antigens, achieving a higher sensitivity in the case of L. pneumophila serogroup 1 soluble antigen. The new EIA was found to be a useful test for the rapid diagnosis of Legionella pneumonia, being a better alternative to the Binax EIA if NCU is used. PMID- 11777661 TI - Helicobacter pylori vacA genotypes, cagA status and ureA-B polymorphism in isolates recovered from an Argentine population. AB - Several reports have evidenced geographic differences in the prevalence of vacA (vacuolating cytotoxin gene) alleles and cagA (cytotoxin-associated gene) status among Helicobacter pylori isolates. We investigated the occurrence of these virulence-associated genes status among our isolates, and their relationship with ulcer disease outcome. Besides, ureA-B polymorphism was studied. One hundred isolates, comprising 32 from patients with ulcer disease (UD) and 68 from patients with non-ulcer dyspepsia (NUD), were analyzed. Eighty-four percent of isolates were cagA-positive without statistically significant difference in prevalence between patients with UD or NUD. Genotype vacA-s1m1 was predominant, although unlike other South American regions, subtype s1am1 occurrence was higher than s1b. The multivariate model used to estimate the predictive value of cagA and vacA status for UD development disclosed infection with vacA-s1am1 isolates as the only variable that increased the risk of UD onset. ureAB fingerprinting showed considerable genetic divergence among isolates, however, confirmed that certain DNA banding profiles are conserved worldwide. PMID- 11777662 TI - Aspergillus: rising frequency of clinical isolation and continued susceptibility to antifungal agents, 1994-1999. AB - We investigated the frequency of clinical isolation and the in vitro susceptibility to antifungal agents of Aspergillus species obtained from patients at the Detroit Medical Center from January 1994 to December 1999. During this period, 593 clinical isolates of Aspergillus species [406 A. fumigatus, 68%; 82 A. niger, 14%; 42 A. flavus, 7%; 63 Aspergillus spp., 11%] were recovered from hospitalized patients. From January 1996 to December 1999, approximately 2.5-4.5 fold yearly increase of the number of aspergillus isolates occurred compared to that of 1994. Conidial suspensions from clinical isolates were prepared and their in vitro susceptibility to amphotericin B and three azoles were determined. All four agents examined were extremely active. The minimum inhibitory concentrations (MIC(90)) (microg/mL) of amphotericin B, itraconazole, voriconazole and posaconazole for A. fumigatus (n = 406) were 0.5, 1.0, 0.5 and 0.25. Similar values were noted for non-A. fumigatus isolates. A year-to-year comparison of the MIC(90) of the four agents for A. fumigatus and non-A. fumigatus isolates over the 6-year study period showed no significant differences. Our study showed a steady increase in the frequency of clinical isolation of Aspergillus species; and the organism has remained susceptible to amphotericin B/triazoles without any change in susceptibility levels during the 6-year study period. PMID- 11777663 TI - Effect of routine use of a multiplex PCR for detection of vanA- and vanB- mediated enterococcal resistance on accuracy, costs and earlier reporting. AB - A multiplex PCR (MPCR) for detection of vanA-and vanB-mediated resistance to vancomycin was optimized and adapted for use in the routine microbiology laboratory. Consecutive specimens (1196) submitted for vancomycin resistant Enterococci (VRE) surveillance were processed by clinical technologists on Bile Esculin Azide Agar containing 6 mg/L vancomycin (BEAA/Vanco6) plates and 466 showing black colony growth were processed by conventional biochemical testing (CBT) and by MPCR. CBT identified 208 VRE positives. MPCR detected 205 of the CBT positives plus an additional 10. Analysis of the discordant specimens determined that 5 CBT- negative/MPCR-positive specimens also contained Enterococci with vanC resistance, 3 CBT-positive/MPCR-negative specimens were true positives, and 5 CBT negative/MPCR-positive specimens occurred due to technical error. The sensitivity and specificity of MPCR were 98.4% and 96.1%. MPCR identifications of VRE were achieved approximately 48 h earlier than CBT and at 60% of the costs. PMID- 11777664 TI - Comparative evaluation of two hemagglutination tests for the detection of anti Helicobacter pylori antibodies. AB - Two hemagglutination assays (IHAs) for detecting anti-H. pylori antibodies were evaluated. In 257 patients, both tests revealed sensitivity or specificity values between 71-79% or 81-82%, respectively, which were lower than those of an anti-H. pylori ELISA. Notably, the sensitivities of both IHAs varied in subgroups of patients between 48-95%. Based on the validation, the IgG-ELISA is superior to both IHAs tested, and therefore, should be used in routine diagnostics. PMID- 11777665 TI - Assessment of BMS284756 MIC and 5-microg disk diffusion quality control studies tested against seven American type culture collection strains. AB - BMS284756 is a novel des-fluoro(6)-quinolone with antimicrobial activity similar to recently developed fluorinated quinolones. The purpose of this investigation was to determine the appropriate disk diffusion and MIC quality control (QC) ranges for BMS284756 when used against commonly tested QC strains (M23-A2). The BMS284756 5-microg disk content was tested against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Hemophilus influenzae ATCC 49247, Streptococcus pneumoniae ATCC 49619 and Staphylococcus aureus ATCC 25923. In addition, Enterococcus faecalis ATCC 29212 and S. aureus ATCC 29213 were evaluated by the broth microdilution method. Seven laboratories tested 2 disk lots on 3 agar media or 3-4 broth lots over a 10 day period. A total of 420 zone diameter values and 210 or 280 MIC values per organism were generated. The following disk diffusion and MIC QC ranges were suggested for BMS284756 and the seven QC strains: E. coli ATCC 25922 (28-35 mm/0.004-0.016 microg/mL), E. faecalis ATCC 29212 (0.03-0.25 microg/mL), S. aureus ATCC 25923 (30-36 mm), S. aureus ATCC 29213 (0.004-0.016 microg/mL), P. aeruginosa ATCC 27853 (19-25 mm/0.5 2 microg/mL), H. influenzae ATCC 49247 (33-41 mm/0.002-0.008 microg/mL), S. pneumoniae ATCC (26-33 mm/0.016-0.06 microg/mL). The proportion of participant results observed within the proposed ranges was 97.4-98.8% and 94.6-100% for the disk diffusion and MIC tests, respectively. PMID- 11777666 TI - Outcomes monitoring in Minnesota: treatment implications, practical limitations. AB - Minnesota developed its treatment outcomes monitoring system to evaluate its service delivery system and to identify specific ways to enhance treatment outcomes. Standardized patient and treatment data were collected for all outpatient and inpatient admissions, and an assessment interview and weekly treatment services records were completed for 4953 adults and 387 adolescents who consented to participate in the outcomes study. Six-month follow-up interviews were completed for 64.4% of these adults and 83.5% of these adolescents. The study identified predictors of treatment completion and outcome for adults and adolescents, and predictors of outcome by setting for adults. The study also examined results for programs designed especially for adolescents, women, and culturally specific populations, as well as the relationships to outcomes of ancillary services and continuing care activities. Anticipated policy and program design changes resulting from the findings are discussed, along with the practical limitations of conducting a state outcomes monitoring system. PMID- 11777667 TI - Effectiveness of a stand-alone aftercare program for drug-involved offenders. AB - A study was made of the effectiveness of an aftercare program operating in conjunction with area outpatient drug free treatment programs while organizationally independent of those programs. Parolees and probationers mandated to treatment were assigned to aftercare on the basis of residence in the catchment areas in which aftercare facilities were located (n = 32) and randomly to aftercare (n = 62) and control (n = 51) when not a resident in a catchment area. No outcome differences were found between aftercare groups based on proximity to facility. At 6 months postbaseline the combined aftercare group showed significantly lower levels of criminal activity and frequent drug use as compared to controls. At 12 months postbaseline there was an attenuation of group differences with only tendencies toward significance obtained for lower levels of frequent drug use by the aftercare group. The findings are discussed in terms of the relevance of community variables for programming and for understanding long term treatment outcomes. PMID- 11777668 TI - The impact of impulsivity on cocaine use and retention in treatment. AB - To determine whether impulsivity was related to severity of drug use and treatment outcome, 50 cocaine dependent subjects underwent baseline measures of severity of current cocaine use and the Barratt Impulsiveness Scale (BIS-11). The hypothesis of the study was that there would be a significant correlation between impulsivity and cocaine use severity. As predicted, there was a significant correlation between BIS-11 total scores and self-reported average daily cocaine use as well as cocaine withdrawal symptoms. A subset of 35 patients underwent a 12-week double-blind placebo controlled trial of buspirone and group therapy. Subjects with high baseline impulsivity remained in the study a significantly shorter period than did subjects with lower baseline impulsivity. This study shows that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment. PMID- 11777669 TI - Exercise attitudes and behaviors among persons in treatment for alcohol use disorders. AB - The present study investigated self-reported exercise behaviors and exercise related attitudes in a sample (N = 105) of adults in treatment for alcohol use disorders (AUD) (abuse or dependence). Slightly less than half (47%) of participants reported engaging in regular physical exercise (3 times per week or more). Level of alcohol dependence was not significantly associated with level of physical exercise activity. Level of nicotine dependence was significantly and negatively associated with physical activity level. Nicotine dependence and level of depressive symptoms were both significantly negatively associated with self efficacy for physical exercise (SPE). Exercise self-efficacy mediated the relationship between nicotine dependence and physical activity level. Tension and stress reduction were among the most strongly endorsed of the perceived benefits of physical activity. Other perceived benefits included more positive outlook and increased self-esteem. Financial costs associated with exercise, lack of motivation, and time constraints were among the most common perceived barriers to exercise in this sample. Together, these preliminary data indicate that exercise based interventions are may be well-received by those early in recovery from AUDs. PMID- 11777670 TI - A multiple risk factor approach for predicting DWI recidivism. AB - A sample of DWI (driving while impaired) offenders was studied to compare various approaches for predicting reoffenses over a 4-year period. Logistic regression yielded multivariate predictor equations that were significant statistically, but were not helpful to clinicians in assessing risk for reoffending. As a different approach, five predictor variables that were consistently correlated with reoffense status were examined to determine the cut score at which the repeat offense rate exceeded the base rate. These were combined to yield the number of risk factors (from 0 to 5) for each offender. This method, used for the original and a hold-out sample, yields results as accurate as those derived from a logistic regression model that includes all the risk variables, and allows clinicians to classify offenders into low and high risk categories in a straightforward manner. Nearly half of offenders with four or five risk factors (age, years of education, arrest blood alcohol concentration (BAC), score on the receptive area scale of AUI and raw score on the MacAndrews scale of MMPI-2) were rearrested compared to the base rate (25%). However, this method is not sufficiently precise to accurately predict which individuals will and will not be rearrested. Although generalizability of specific algorithms across populations needs to be examined, this method appears promising as a clinically accessible way to classify, in a given offender population, those who are most likely to repeat the offense. PMID- 11777671 TI - Olanzapine treatment for patients with schizophrenia and substance abuse. AB - The objective of this study was to evaluate the efficacy and safety of olanzapine in patients with schizophrenia and comorbid substance abuse disorders. Thirty patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder as well as criteria for substance abuse or substance dependence, were treated in a 12-month prospective, open-label trial of olanzapine. Patients were evaluated with multiple efficacy and safety measures at baseline and then monthly thereafter. Statistically significant improvement was noted in psychopathology, levels of hope, and safety measures. Seventy percent (n = 21) of the patients achieved early full substance abuse remission at the end of the study period, while 30% (n = 9) achieved early partial substance abuse remission. Our results indicate that olanzapine treatment improved psychopathology, increased hopefulness, and reduced antipsychotic-associated side effects. The benefits observed with olanzapine treatment may contribute to the patients' substance abuse remission. PMID- 11777672 TI - The effect of a stage-matched and tailored intervention on repeat mammography(1). AB - BACKGROUND: Our objective was to determine whether a tailored, stage-matched educational intervention, guided by the transtheoretical model (TTM), would increase rates of repeat-screening mammography. DESIGN SETTING/PARTICIPANTS: A total of 1324 women (N=1026 after attrition) aged 50 to 74 years were recruited from a staff-model health maintenance organization. Some of the women were not due for mammograms at the time of recruitment. INTERVENTION: Women were randomly assigned to one of three intervention conditions: Group 1, no educational materials (usual care); Group 2, standard materials; and Group 3, stage matched/tailored materials. Women in Groups 2 and 3 received a mailed education packet after both a baseline and a follow-up telephone interview. All women in Group 2 received the same materials regardless of differences in baseline mammography-related attitudes and behaviors. Each woman in Group 3 received materials based on her stage of adoption for mammography and TTM constructs. MAIN OUTCOME: Using clinical records, repeat screening was defined as receipt of a second mammogram within 14 months after obtaining an initial postbaseline mammogram. RESULTS: Women in Group 3 were more likely to obtain repeat-screening mammograms than women in Group 1 (44.2% vs 35.8%; adjusted rate ratio = 1.29, 95% confidence interval [CI]=1.11-1.46; adjusted rate difference = 0.06, 95% CI=-0.01 0.13). The screening percentage in Group 2 was intermediate (39.3%), and did not differ from either Group 3 or Group 1. CONCLUSIONS: The effect of the stage matched/tailored intervention was sustained for repeat screening, although no educational materials were delivered to coincide with the timing for a second mammogram. However, the stage-matched/tailored intervention was not sufficient to have a substantial impact on screening beyond the effect of standard educational materials. Future interventions may need to administer "booster" sessions to increase repeat screenings. PMID- 11777673 TI - How consistently do women report lifetime mammograms at successive interviews? AB - BACKGROUND: Little data exist on the reliability of self-reported regular mammography use measures. We used data from two successive interviews of 892 women aged 50 to 74 years without a history of abnormal mammograms to investigate how consistently women report their lifetime number of mammograms. METHODS: We added an estimated number of mammograms obtained between interviews to the baseline report to create a revised baseline report for comparison with the follow-up report. We then examined the correlation in paired reports, the level of agreement between paired reports, and factors associated with consistent reporting. RESULTS: Spearman rank correlation between paired reports was 0.73. Agreement between paired reports dropped with increasing lifetime number of mammograms. After adjustment for mammography use, women's characteristics did not appear to be strongly associated with consistent reporting. CONCLUSIONS: Self reported lifetime number of mammograms is a reasonably consistent measure for younger women or women with less mammography experience, but it is less reliable for women with long mammography histories. In these women, it may be useful to distinguish those who obtain regular screening from those who do not. Assessing reliability as well as validity for other measures of regular mammography use will allow additional measures to be identified. PMID- 11777674 TI - Can personal health record booklets improve cancer screening behaviors? AB - BACKGROUND: Despite the widespread use of written health education materials as interventions, relatively few studies have adequately evaluated the effectiveness of such materials on changing healthcare behaviors in the general population. SETTING/PARTICIPANTS: The study consisted of ten matched pairs of small rural towns in New South Wales, Australia, with a total combined population of approximately 25,000 in both the intervention and control group towns. A randomized controlled trial was used. INTERVENTION: Personal Health Record Booklets (PHRBs) that include the latest evidence-based recommendations for reducing risk of cancer and cardiovascular disease were developed using leading behavioral change theories to maximize effectiveness. The booklets included an explanatory letter, a gender-specific Better Health Booklet, and a gender specific Better Health Diary. Following a media campaign, the PHRBs were mailed to all residents aged 20 to 60 years (about 12,600 people) in the ten intervention towns. Family practitioners in the intervention towns were recruited to support and encourage people to use the PHRBs. MAIN OUTCOME MEASURES: Health Insurance Commission data for Papanicolaou (Pap) tests, mammograms, and skin operations were obtained for 5 years before the intervention, and 3 months and 1 year after the intervention. RESULTS: No significant increases in the rates of Pap tests, mammograms, and skin operations were detected in either short- or long term follow-ups. CONCLUSIONS: While PHRBs may represent an inexpensive, easy-to produce, and time-efficient method of communicating information to the general population, it appears unlikely that any significant behavioral change will result unless such materials are targeted toward high-risk groups or constitute the first intervention for a particular risk factor. PMID- 11777675 TI - Neighborhood characteristics associated with the location of food stores and food service places. AB - BACKGROUND: Although the relationship between diet and disease is well established, sustainable dietary changes that would affect risk for disease have been difficult to achieve. Whereas individual factors are traditional explanations for the inability of some people to change dietary habits, little research has investigated how the physical availability of healthy foods affects individuals' diets. This study examines the distribution of food stores and food service places by neighborhood wealth and racial segregation. METHODS: Names and addresses of places to buy food in Mississippi, North Carolina, Maryland, and Minnesota were obtained from respective departments of health and agriculture. Addresses were geocoded to census tracts. Median house values were used to estimate neighborhood wealth, while the proportion of black residents was used to measure neighborhood racial segregation. RESULTS: Compared to the poorest neighborhoods, large numbers of supermarkets and gas stations with convenience stores are located in wealthier neighborhoods. There are 3 times fewer places to consume alcoholic beverages in the wealthiest compared to the poorest neighborhoods (prevalence ratio [PR]=0.3, 95% confidence interval [CI]=0.1-0.6). Regarding neighborhood segregation, there are 4 times more supermarkets located in white neighborhoods compared to black neighborhoods (PR=4.3, 95% CI=1.5-12.5). CONCLUSIONS: Without access to supermarkets, which offer a wide variety of foods at lower prices, poor and minority communities may not have equal access to the variety of healthy food choices available to nonminority and wealthy communities. PMID- 11777676 TI - Increased risk of heart disease and stroke among foreign-born females residing in the United States. AB - BACKGROUND: Although the number of foreign-born people residing in the United States is at its highest point in 80 years, a mortality analysis of the foreign born has not been conducted since 1989. This article provides an update of mortality rates among the foreign born in the United States and, in particular, examines mortality rates from heart disease among foreign-born females. METHODS: We calculated mortality rates for U.S.-born and foreign-born people for all causes-ischemic heart disease, stroke, neoplastic disease, hypertensive diseases, diabetes, accidents, infectious disease, and chronic obstructive pulmonary disease-for 1997. Death data were obtained from the 1997 Multiple Cause of Death data file, and population data were obtained from the 1997 Current Population Survey. RESULTS: While all-cause, age-adjusted mortality rates for foreign-born people are significantly lower than for native-born people, deaths due to ischemic heart disease and stroke are significantly higher among foreign-born females than native-born females (161.63 and 58.24 deaths, respectively, per 100,000 foreign-born females vs 122.01 and 49.39 deaths per 100,000 native-born females). CONCLUSIONS: Foreign-born females appear to be at greater risk of death from ischemic heart disease and stroke than native-born females. Future research efforts are needed to determine which foreign-born groups are most at risk for heart disease and stroke so that targeted prevention efforts can be initiated. PMID- 11777677 TI - Predictors of digital rectal examination in U.S. Latinos. AB - BACKGROUND: Little is known about prostate and colorectal cancer knowledge, attitudes, and screening practices among U.S. Latino men. Even less is known about the population's subgroup variations. This study assessed predictors of having obtained digital rectal examinations (DREs) among four Latino subgroups. METHODS: Findings in this report are based on a cross-sectional telephone survey conducted between October 1993 and June 1994 as part of a multisite demonstration project for cancer prevention and control. The survey was conducted in eight U.S. cities identified via census data as having relatively high concentrations of targeted Latino subgroups. The analysis included 1499 Latino men aged > or = 40 who self-identified as Central American, Cuban American, Mexican American, or Puerto Rican. RESULTS: Overall, 53% of the sample reported ever having had a DRE and 68% reported ever having heard of the procedure. For all subgroups, the only significant predictor for obtaining a DRE was "ever heard of DRE." "Having your doctor discuss DRE" was a significant factor for Mexican Americans and Puerto Ricans. CONCLUSIONS: The lack of a universal DRE cancer-screening model among Latino groups highlights the need to address barriers in the context of the population's diversity. Ecologic approaches and clinician communication with Latinos need to be tailored to accommodate subgroup differences in knowledge, attitude, and practices related to DRE. PMID- 11777678 TI - Elevated blood pressure among U.S. adults with diabetes, 1988-1994. AB - BACKGROUND: Recent guidelines and clinical trial results emphasize the importance of controlling blood pressure among people with diabetes. We estimated the prevalence of elevated blood pressure among U.S. adults with diagnosed diabetes, and examined the extent to which elevated blood pressure is being treated and controlled. METHODS: The Third National Health and Nutrition Examination Survey (1988-1994), a probability survey of the civilian, non-institutionalized population of the United States, consisted of an interview and physical examination, which included blood pressure measurement. Survey participants included 1507 adults (aged > or = 18 years) with self-reported diabetes. Among people with self-reported diabetes, we estimated elevated blood pressure (mean blood pressure of > or = 130/85 mm Hg or use of antihypertensive medication); awareness (prior diagnosis of hypertension); treatment (antihypertensive medication use); and control (mean blood pressure of <130/85 or <140/90). RESULTS: In the 1988-1994 period, 71% (95% confidence interval [CI]=+/-4.4%) of all U.S. adults with diabetes had elevated blood pressure. The prevalence of elevated blood pressure increased with age and was high among both men and women and among Mexican Americans, non-Hispanic blacks, and non-Hispanic whites. Among those with elevated blood pressure, 71% (95% CI=+/-4.1%) were aware and 57% (95% CI=+/-4.2%) were treated, but only 12% (95% CI=+/-3.2%) had mean blood pressure <130/85 and 45% (95% CI=+/-4.9%) had mean blood pressure <140/90. Control of blood pressure was least common among older people. CONCLUSIONS: All people with diabetes-regardless of age, gender, and race and ethnicity-may benefit from efforts to prevent hypertension. The control of elevated blood pressure is inadequate and broad-based efforts are needed to improve blood pressure control. PMID- 11777679 TI - Physicians' attitudes and beliefs concerning alcohol abuse prevention in adolescents. AB - BACKGROUND: Primary alcohol abuse-prevention services delivered to adolescents are inadequate, despite the fact that alcohol abuse is a major health problem. Physicians' attitudes and beliefs regarding primary prevention of adolescent alcohol abuse and appropriate onset ages of alcohol use may be useful in understanding why delivery of prevention services is inadequate, but as yet has not been investigated. OBJECTIVES: To examine (1) physicians' attitudes and beliefs regarding alcohol abuse prevention and practice, and (2) correlates of these attitudes and beliefs, including the delivery of primary alcohol abuse prevention services to adolescents. METHODS: A national, stratified random sample of pediatricians and family practitioners was drawn from the American Medical Association's Masterfile Registry. Inclusion criteria included active medical practice and seeing at least one adolescent per week. The response rate was 63%, resulting in a final sample of 1842 physicians. Participants were queried about their practice, alcohol use, attitudes and beliefs, and delivery of alcohol related screening and education to adolescents. RESULTS: On average, physicians reported providing alcohol-related screening to 40.3% (standard error [SE]=0.6) and education to 52.0% (SE=0.8) of their adolescent patients. Participants had positive attitudes toward adolescents, believed that prevention was important, and approved of alcohol screening early in adolescence, but did not feel very comfortable about their adolescent alcohol-management skills. Except for ceremonial use, most physicians did not believe in underage drinking. Attitudes and beliefs were significantly related to the delivery of alcohol screening (R(2)=0.34, p < 0.001) and education (R(2)=0.18, p < 0.001). Participants who delivered more screening and education had more positive beliefs in the importance of prevention (beta=0.14 and beta=0.13, respectively; p < 0.001); approved of early alcohol screening (beta=0.29 and beta=0.09, respectively; p < 0.001); and were more comfortable with their alcohol management skills (beta=0.31 and beta=0.28, respectively; p < 0.001). A profile of physicians with positive attitudes and beliefs is presented. CONCLUSIONS: Physician attitudes and beliefs are associated with variations in alcohol screening and education services delivered to adolescents. A better understanding of physicians' attitudes and beliefs can be useful in providing physician education and training aimed at improving primary alcohol-abuse prevention. PMID- 11777680 TI - The accuracy of primary care patients' self-reports of prostate-specific antigen testing. AB - BACKGROUND: The accuracy of reports made by male primary care patients of previous screening for prostate cancer with the prostate-specific antigen (PSA) assay is important for clinical practice, surveillance, and research. METHODS: As part of a clinical trial that evaluated a decision aid for prostate cancer screening, 133 male primary care patients, aged 45 to 70 years, were contacted 1 year after enrollment and asked whether they had received PSA testing. To corroborate these self-reports, each patient's clinic and hospital medical records were reviewed for evidence of PSA test results. RESULTS: The raw percentage agreement between self-reported PSA testing and the medical records was 74.4% (kappa=0.48). When compared to the findings of the medical record reviews, apparent overreporting by some patients was explained by problems with recalling the test within the 1-year time frame (4.5%) and by having been tested outside of the medical center (5.3%). Uncertainty about having been tested was reported by six (4.5%) patients with PSA test results in their medical records. Misreported testing could not be explained for 11.3% of patients. Patients who had not completed high school were 2.7 times more likely to misreport PSA testing (95% confidence interval, 1.61-3.87). CONCLUSIONS: The accuracy of primary care patients' self-reports of previous PSA testing is questionable. Errors in reporting are due largely to problems with recalling a test within a specific time frame or to testing outside of the primary care setting. Under-reporting is a problem for patients uncertain of previous testing. PMID- 11777681 TI - Self-directed learning in population health. a clinically relevant approach for medical students. AB - BACKGROUND: In this article, we describe the education model used to integrate population health learning into a new 4-year medical program at the University of Sydney. METHOD: Our two-pronged approach aims to prepare third-year students to integrate population health thinking into their day-to-day clinical reasoning and to equip them with skills to investigate specific population health topics. We provide an example of a student-led, small-group session on health issues for disadvantaged populations, along with an outline of our assessment and evaluation methods. This innovative course illustrates one approach to the challenge of motivating students to bridge the gap between their interest in the medical care of individual patients and the healthcare needs of whole populations. RESULTS/CONCLUSIONS: Students performed adequately in the assessments required for progression to the next year of the program. Students rated the case-based exercises; self-directed learning; on-line and library resources; tutor facilitation; and student-led, small-group sessions as effective methods for learning. PMID- 11777684 TI - Education for population health. PMID- 11777685 TI - Treatment of children with elevated blood lead levels. PMID- 11777688 TI - Intraocular lens biocompatibility. PMID- 11777689 TI - Misgivings about simultaneous bilateral cataract extraction. PMID- 11777691 TI - Ethical issue in simultaneous bilateral cataract extractions. PMID- 11777693 TI - Animal model for teaching phacoemulsification. PMID- 11777694 TI - Silicone oil removal through a posterior capsulorhexis simultaneously with phacoemulsification. PMID- 11777695 TI - Anterior chamber maintainer versus viscoelastic material for IOL implantation. PMID- 11777697 TI - Sympathetic ophthalmia as a preoperative consideration in adults having anterior segment revision for trauma sustained in childhood. PMID- 11777698 TI - Laser in situ keratomileusis after PKP. PMID- 11777700 TI - Plastic exfoliations from the cartridge after implantation of a hydrophilic acrylic lens without viscoelastic material. PMID- 11777702 TI - Entoptic narration during phacoemulsification by an ophthalmologist. PMID- 11777703 TI - Cortical removal simplified by J-cannula irrigation. AB - Subincisional cortical removal is one of the more specific obstacles impeding the performance of uneventful cataract extraction. In this technique, staged use of a J-cannula irrigates the cortex remaining after phacoemulsification, particularly in the subincisional space. This is followed by standard automated aspiration. The irrigation procedure is independent of a small pupil or capsulorhexis and typically allows for complete cortical cleanup in less than 1 minute. The details of the procedure, used in more than 3000 cases, are reported. PMID- 11777704 TI - Modified transscleral suture for sulcus fixation of posterior chamber lenses. AB - We describe a modified technique to minimize the risk of hypotony during the placement of transscleral anchoring sutures. An anchor thread is used to transsclerally fixate a posterior chamber intraocular lens (IOL). The IOL is placed precisely and without trauma. The technique was used in 17 patients. Postoperatively, all IOLs were well centered. Visual acuity increased from a preoperative mean of 0.25 to a postoperative mean of 0.40. The mean postoperative refraction was -0.75 diopter (D) (range +0.50 to -4.50 D). Longer phases of hypotony do not occur, and the use of CIF needles can be omitted. PMID- 11777705 TI - Laser-assisted subepithelial keratectomy for the correction of myopia. AB - PURPOSE: To evaluate the results of laser-assisted subepithelial keratectomy (LASEK) for spherical and spherocylindrical myopia. SETTING: Indiana Eye Institute, South Bend, Indiana, USA. METHODS: In a retrospective noncomparative single-surgeon interventional case series, outcomes in 222 consecutive eyes with myopia ranging from -1.25 to -11.25 diopters (D) and astigmatism up to +2.25 D treated with LASEK using a VISX Star S2 excimer laser were analyzed 4 days, 2 weeks, and 3, 6, and 12 months after surgery. RESULTS: The uncorrected visual acuity (UCVA) was 20/40 or better in 84% of eyes at 4 days and in 98% at 2 weeks. At 12 months, in 84 eyes, the UCVA was 20/15 in 16 eyes (19.0%), 20/20 in 53 (63.1%), and 20/25 in 15 (17.9%). There was no loss of best spectacle-corrected visual acuity (BSCVA), and no eye required retreatment. CONCLUSION: Laser assisted subepithelial keratectomy for myopia provided excellent refractive and visual results with no loss of BSCVA and no serious complications. Subjective results and other measures of visual function need further evaluation. PMID- 11777706 TI - Incidence of intraoperative flap complications in laser in situ keratomileusis. AB - PURPOSE: To evaluate the incidence of intraoperative flap complications in laser in situ keratomileusis (LASIK) and compare the incidence between eyes and between the Hansatome and Automated Corneal Shaper (Bausch & Lomb) microkeratomes. SETTING: Open-access outpatient excimer laser surgical facility. METHODS: A retrospective analysis was done of 84711 primary LASIK cases performed between November 1998 and May 2000 in 28 national open-access laser facilities. The intraoperative flap complications were identified and categorized into type of complication, eye involved, and microkeratome type. All cases used the Automated Corneal Shaper or the Hansatome microkeratome. RESULTS: Two hundred fifty-six complications (0.302%) were identified: 29 failures to achieve intraocular pressure (0.034%), 84 partial flaps (0.099%), 59 buttonholes (0.070%), 74 thin or irregular flaps (0.087%), and 10 free flaps (0.012%). There were 134 right eye complications and 122 left eye complications (P =.45). No patient developed an intraoperative flap complication in both eyes. A comparison of Hansatome and Automated Corneal Shaper microkeratomes was possible for the cases performed between December 1999 and May 2000: 46 of 28 201 Hansatome procedures (0.16%) had a complication versus 21 of 329 Automated Corneal Shaper procedures (6.38%). This difference was statistically significant (P <.005). CONCLUSION: The incidence of intraoperative flap complications during LASIK was acceptably small. The overall complication rate was similar in both eyes. The Hansatome was associated with a lower complication rate than the Automated Corneal Shaper. PMID- 11777707 TI - Implantable contact lens for high myopia. AB - PURPOSE: To evaluate the efficacy, safety, and biocompatibility of a collagen polymer implantable contact lens (ICL) (Staar Collamer) as a posterior chamber phakic intraocular lens (IOL) to correct high myopia. SETTING: Departments of Ophthalmology, Helsinki University Central Hospital, Helsinki, and Tampere University Hospital, Tampere, Finland. METHODS: A Staar Collamer posterior chamber phakic IOL was implanted in 38 eyes of 22 patients with a mean age of 39 years (range 24 to 54 years). The mean preoperative myopia was -15.10 diopters (D) (range -7.75 to -29.00 D). Surgical implantation was performed through a 3.0 mm clear corneal sutureless incision using paraocular anesthesia. The patients were followed clinically up to 3 years. The mean follow-up was 13.6 months (range 6 to 24 months) for refractive data and 22.3 months (range 6 to 35 months) for complications. The possible inflammatory response to the ICL was measured using a laser flare meter in 12 eyes. RESULTS: Postoperatively, all eyes had a significant increase in uncorrected visual acuity, allowing all but 3 patients (5 eyes) to manage most activities without spectacles. The mean spherical equivalent refraction at the last examination was -2.00 D +/- 2.48 (SD) (range +0.13 to 13.00 D), within +/-1.00 D of the targeted refraction in 31 eyes (81.6%) and within +/-0.50 D in 27 eyes (71.1%). In eyes in which the preoperative myopia was less than -18.00 D (n = 28), the achieved refraction was within +/-1.00 D of the intended refraction in 27 eyes (96.4%) and within +/-0.50 D in 24 eyes (85.7%). The refraction remained stable with a statistically insignificant change (P >.05) at each interval during the follow-up. The best corrected visual acuity (BCVA) improved by 1 or more lines in 23 of 32 eyes (71.9%) at 1 year. Two eyes (6.3%) lost 1 line of BCVA. Laser flare photometry showed normal aqueous flare values (11.71 +/- 6.61 photon counts/ms) in the 12 eyes measured at least 6 months after ICL implantation. Pupillary block glaucoma requiring surgical intervention occurred in 3 patients (7.9%). One patient (2.6%) developed cataract 1.5 years after ICL implantation; both ICLs were removed, and the refractive errors were corrected by lensectomy and implantation of low-power posterior chamber IOLs. One patient (2.6%) showed progression of dry macular degeneration at 17 months. CONCLUSION: At 1 year, ICL implantation had good visual and refractive results with excellent biocompatibility. Long-term follow-up is required to confirm that significant complications do not occur in most patients over time. PMID- 11777708 TI - Laser in situ keratomileusis enhancement for consecutive hyperopia after myopic overcorrection. AB - PURPOSE: To assess the efficacy, predictability, and safety of laser in situ keratomileusis (LASIK) for the treatment of consecutive hyperopia after myopic LASIK. SETTING: Stanford University School of Medicine, Stanford, California, USA. METHODS: In a retrospective study, 36 eyes of 30 patients with consecutive hyperopia after myopic LASIK had LASIK retreatment using the VISX S2 excimer laser. Primary outcome variables including uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, complications, and vector analysis were evaluated preoperatively and 1 day and 3 months postoperatively. RESULTS: The mean spherical equivalent decreased from +1.52 diopters (D) +/- 0.55 (SD) (range +0.63 to +2.63 D) preoperatively to -0.10 +/- 0.52 D (range -1.25 to +1.50 D) 3 months after retreatment. The UCVA was 20/20 or better in 24 eyes (66.7%) and 20/40 or better in 34 eyes (94.4%). Twenty eyes (55.5%) were within +/-0.5 D of the intended correction and 34 eyes (94.4%), within +/-1.0 D. No eye lost 2 or more lines of BSCVA. One eye (2.8%) developed diffuse lamellar keratitis that resolved without sequelae, and 2 eyes (5.6%) developed nonprogressive epithelial ingrowth that did not require removal. CONCLUSIONS: Laser in situ keratomileusis retreatment for consecutive hyperopia following myopic LASIK was an effective, predictable, and safe procedure. Long term follow-up is needed to assess stability. PMID- 11777709 TI - Correction of pseudophakic anisometropia with the Staar Collamer implantable contact lens. AB - PURPOSE: To assess the role of the Staar Surgical implantable contact lens (ICL) for the correction of pseudophakic anisometropia. SETTING: Oxford Eye Hospital, Oxford, and Rosen Eye Center, Alexandra Hospital, Manchester, United Kingdom. METHODS: Six patients with pseudophakic anisometropia ranging from 2.0 to 7.9 diopters (D) (mean 4.4 D) had ICL implantation as an alternative to intraocular lens (IOL) exchange or conventional piggyback IOLs. RESULTS: All patients had a reduction in anisometropia to asymptomatic levels. The mean reduction was 3.15 D. No patient experienced adverse effects. CONCLUSIONS: The implantable contact lens offers an alternative approach to the management of pseudophakic anisometropia that avoids some of the risks associated with IOL exchange, corneal refractive surgery, and conventional piggyback IOLs. PMID- 11777711 TI - Refractive error and visual outcome after cataract extraction. AB - PURPOSE: To determine the range of biometry prediction error of the postoperative refraction and the visual outcome after cataract surgery. SETTING: Postgraduate teaching hospital. METHODS: Refraction and visual outcomes were recorded prospectively for a consecutive case series of 1817 cataract procedures. Complete preoperative and postoperative data were available for 1676 eyes (92.4%). The paired mean error of the difference between the predicted and achieved refraction, the percentages falling within +/-0.50 diopter (D), +/-1.00 D, and +/ 2.00 D, and the values that contained 99% of data points were then calculated. The number that achieved a final Snellen visual acuity of 6/12 was determined in all eyes and in eyes without preoperative ocular comorbidity. This analysis was repeated in 1265 eyes that received a single intraocular lens (IOL) design (C10UB/C11UB) after phacoemulsification through a clear corneal incision. RESULTS: The paired mean error of the difference between the predicted and achieved postoperative refraction in all eyes was -0.32 D +/- 1.05 (SD); 72.3% of eyes were within +/-1.00 D of the planned refraction, with bounds of 99% of observation of +2.92 D and -3.98 D. In the single IOL group, the paired mean error was -0.32 +/- 0.94 D; 74.2% of eyes fell within +/-1.00 D of the planned refraction, with bounds of 99% of observation of +2.54 D and -3.81 D. Axial length did not determine the magnitude of the biometry prediction error. At discharge from the service, 86.9% of all eyes and 95.4% of eyes without preoperative ocular comorbidity achieved a final corrected Snellen acuity of 6/12. CONCLUSION: These data provide benchmark information that can be used to monitor clinical practice. PMID- 11777710 TI - Uveal and capsular biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses. AB - PURPOSE: To evaluate the long-term response of 6 types of 3-piece intraocular lenses (IOLs) by assessing the cellular reaction on the anterior IOL surface, the behavior of posterior and anterior capsule fibrosis, and flare. SETTING: Department of Ophthalmology, Medical School, University of Vienna, Vienna, Austria. METHODS: One hundred eighty eyes were prospectively randomized to receive 1 of 6 IOLs: hydrophilic acrylic Hydroview (Bausch & Lomb) or MemoryLens (ORC); hydrophobic acrylic AcrySof MA60BM (Alcon) or AMO Sensar AR40 (Allergan); hydrophobic silicone CeeOn 920 or CeeOn 911A (Pharmacia). The patients had standardized cataract surgery, postoperative medication, and follow-up. One year after surgery, 155 eyes were assessed. The cellular reaction was evaluated by specular microscopy of the anterior IOL surface. Anterior and posterior capsule opacification (PCO) was assessed semiquantitatively by biomicroscopy. Flare was measured with a Kowa FC-1000 laser flare-cell meter. RESULTS: Regarding uveal biocompatibility, the hydrophobic acrylic IOLs showed the highest incidence of late foreign-body cell reaction (AcrySof, 30%; AR40, 17%) followed by the hydrophilic acrylic (MemoryLens, 8%; Hydroview, 4%) and silicone (CeeOn 920, 4%; CeeOn 911A, 0%) (P =.0044). In all cases, the cellular reaction was low grade and clinically insignificant. Regarding capsular biocompatibility, some eyes developed lens epithelial cell (LEC) outgrowth on the anterior IOL surface. The highest incidence was in the hydrophilic acrylic group (Hydroview, 85%; MemoryLens, 27%) followed by the hydrophobic acrylic (AcrySof, 4%; AR40, 3%). No silicone IOL had LECs on the anterior surface. The difference among IOL groups was significant (P =.0001). Anterior capsule opacification was more predominant in the hydrophobic IOL groups. Posterior capsule opacification of the central 3.0 mm area was lowest in the groups with a sharp-edged optic (CeeOn 911A, AcrySof) followed by the round-edged silicone (CeeOn 920), hydrophobic acrylic (AR40), and hydrophilic acrylic IOLs (P =.0001). There was a significant difference in flare between the AR40 lens and the Hydroview, MemoryLens, CeeOn 911A, and CeeOn 920 (P <.004). There was no statistically significant difference in the postoperative cell count at 1 year. The power calculation showed that the sample size was sufficient. CONCLUSIONS: The differences in cellular reaction, although clinically mild in normal eyes, indicate that there were more giant cells with hydrophobic acrylic IOLs and an increased tendency toward LEC outgrowth with hydrophilic lenses. The incidence of PCO was lowest in the hydrophobic IOL groups, especially in groups with a sharp-edged optic. Second-generation silicone IOLs with a sharp edge had good uveal and capsular biocompatibility 1 year after surgery. PMID- 11777712 TI - Phacoemulsification in the anterior chamber. AB - PURPOSE: To evaluate anterior chamber phacoemulsification as an alternative to an endocapsular procedure. SETTING: Instituto Oftalmologico de Alicante, Alicante, Spain. METHODS: In this prospective randomized masked clinical trial, 60 eyes of 30 patients had cataract extraction by phacoemulsification. A conventional stop and-chop technique was used in 30 eyes; the other 30 had surgery by the phaco-out technique in which the nucleus was prolapsed into the anterior chamber using extensive hydrodissection. Copious sodium hyaluronate 3.0%-chondroitin sulfate 4.0% (Viscoat) and hydroxypropyl methylcellulose were used to protect the cornea and iris. The phaco time and power, postoperative inflammation, corneal edema (clinically and by pachymetry), and endothelial cell count between groups preoperatively and postoperatively were compared. All patients completed a 3 month follow-up. Postoperative examinations were at 3 days, 2 weeks, and 1 and 3 months. RESULTS: The mean nuclear hardness was 2.67 +/- 0.61 (SD) in the stop-and chop group and 2.65 +/- 0.71 in the phaco-out group. The power-to-time ratio was 18.47 and 18.80, respectively. The mean endothelial cell loss was 11.18% +/- 4.24% in the stop-and-chop group and 11.20% +/- 5.60% in the phaco-out group. There were no significant differences between groups in any parameter (P >.05, independent-sample t test). CONCLUSION: Phacoemulsification in the anterior chamber was as safe as endocapsular phacoemulsification using a stop-and-chop technique. This technique is fast and easier to learn than endocapsular phacoemulsification. PMID- 11777713 TI - Performance comparison of the Alcon Legacy 20000 straight and flared 0.9 mm Aspiration Bypass System tips. AB - PURPOSE: To compare the efficiency of surgical procedures using 2 phacoemulsification tips. SETTING: Wolfe Clinic, Marshalltown, Iowa, USA. METHODS: A randomized prospective study of 256 consecutive cases was conducted. The patients were adults having phacoemulsification by a modified in situ fracture technique. All cases were done by 1 surgeon using the Alcon Legacy 20000 phacoemulsification machine with high-vacuum cassettes and tubing. One of 2 45 degree Aspiration Bypass System (ABS) phacoemulsification tips was used. The straight tip has a 0.9 mm outside diameter (n = 127). The flared tip has a 0.76 mm outside diameter shaft that flares to a 1.02 mm tip (n = 129). Measurements at the time of surgery included metered phacoemulsification time, percentage power used, total phacoemulsification time, and milliliters of balanced salt solution (BSS(R)) used. RESULTS: No posterior capsule tear, vitreous loss, incision thermal damage, incision leak, or suture closure occurred. There were no cases of iris aspiration into the working end of the phacoemulsification needle; however, the iris was aspirated into the ABS opening of the flared tip in 1 case. Similar measurements for the straight and flared tips included, respectively, metered phacoemulsification time, 1.4 minutes each; mean power percentage, 41% and 39%; total phacoemulsification time, 2 minutes 11 seconds and 2 minutes 15 seconds; and overall BSS volume, 77 mL and 75 mL. The anterior capsule tear rates for straight (5.5%) and flared (1.6%) tips were similar. CONCLUSIONS: The flared ABS phaco tip with a 0.76 mm shaft outside diameter provided the physical advantages of shaft diameter reduction and required ultrasonic energy expenditures, BSS volumes, and surgical times similar to those of the straight ABS ultrasonic tip with a 0.9 mm outside diameter. PMID- 11777714 TI - Ultrasonic phacoemulsification using a 1.4 mm incision: clinical results. AB - PURPOSE: To evaluate the intraoperative complications and postoperative results of bimanual phacoemulsification and aspiration using a sleeveless phaco tip inserted through an ultra-small incision. SETTING: Department of Ophthalmology, Jikei University, Tokyo, Japan. METHODS: This study comprised 637 eyes having cataract extraction using conventional phacoemulsification equipment. A 20-gauge phaco tip with the sleeve removed was inserted through a 19-gauge corneal incision. A 20-gauge hooked cannula with the wall thinned to increase the inner diameter was used for infusion. After the crystalline lens was removed, the incision was widened to 2.8 to 4.1 mm and and an intraocular lens (IOL) was implanted. Study parameters were operating time, amount of infusion solution used, incidence of intraoperative complications, and early postoperative results. RESULTS: The mean operating time was 8 minutes 42 seconds. Although the nuclear hardness was grade 4 or above in 35 eyes, there were no cases of thermal burn. The amount of infusion solution and the rate of postoperative decrease in corneal endothelial cell density did not differ greatly from results of conventional methods. This technique induced considerably less corneal astigmatism than surgery using conventional corneal incisions. CONCLUSIONS: A sleeveless phaco tip was used to perform successful bimanual phacoemulsification using conventional phaco machines and familiar surgical techniques. The cataracts were safely removed through an incision of 1.4 mm or smaller that was widened for IOL insertion. PMID- 11777715 TI - Effect of heparin in the irrigation solution on postoperative inflammation and cellular reaction on the intraocular lens surface. AB - PURPOSE: To evaluate the influence of heparin sodium in the irrigation solution on postoperative inflammation and cellular reaction on the anterior surface of a hydrophilic intraocular lens (IOL). SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This randomized prospective single-surgeon study included 50 patients with senile cataract only. Half the patients received 1 mL of heparin sodium (concentration 10 IU/mL) in addition to the regular irrigating solution. In all other respects, the procedure was standardized: clear corneal incision, phacoemulsification, and implantation of a Hydroview foldable hydrogel IOL (Bausch & Lomb). The parameters of inflammation anterior chamber flare and cells-were evaluated with the pupil dilated in a masked fashion using a Kowa FC-1000 laser flare-cell meter 1, 3, 7, 14, and 28 days and 3, 6 and 12 months postoperatively. The cellular reaction was semiquantitatively examined and analyzed by specular microscopy. RESULTS: In both groups, flare and cell values increased on the first postoperative day and successively decreased thereafter. In the first week, the flare and cell values were significantly higher in the group without heparin sodium in the irrigating solution. Subsequently, there were no differences between the 2 groups in flare or cells. At 1 day, the heparin sodium group had statistically significantly fewer IOLs with no cells on the surface. Subsequently, no differences in cellular reaction on the IOL were observed. CONCLUSIONS: Heparin sodium added to the standard irrigating solution reduced disturbances of the blood-aqueous barrier in the early postoperative period. There seemed to be no long-term effect, especially on cellular reaction, on the hydrophilic IOL surface. PMID- 11777716 TI - Comparison of ketorolac tromethamine 0.5% and loteprednol etabonate 0.5% for inflammation after phacoemulsification: prospective randomized double-masked study. AB - PURPOSE: To compare the efficacy of a topical nonsteroidal antiinflammatory agent (ketorolac tromethamine ophthalmic solution 0.5%) and a topical steroid (loteprednol etabonate ophthalmic suspension 0.5%) in controlling inflammation after cataract surgery. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Sixty patients were prospectively and randomly assigned to receive topical treatment with ketorolac tromethamine ophthalmic solution 0.5% or loteprednol etabonate ophthalmic suspension 0.5% starting the day after routine phacoemulsification for cataract extraction. Both patient and investigator were masked to treatment. All patients had uneventful small-incision phacoemulsification with placement of a foldable posterior chamber intraocular lens (IOL). Patients used 1 of the 2 antiinflammatory agents 4 times a day starting 24 hours after surgery. Signs and symptoms of inflammation as documented by external slitlamp examination, intraocular pressure (IOP), and Kowa cell and flare measurements were evaluated on postoperative days 1, 4, 7, and 30. RESULTS: There was no statistically significant difference in any measurement of postoperative inflammation between the 2 groups. There was no difference in objective or subjective cell and flare measurements or in IOP between groups. No patient in either group was removed from the study for lack of treatment efficiency. CONCLUSIONS: Ketorolac tromethamine ophthalmic solution 0.5% was as effective as loteprednol etabonate ophthalmic suspension 0.5% in reducing inflammation after routine phacoemulsification and IOL implantation. These results suggest that ketorolac tromethamine 0.5% is a safe and effective antiinflammatory alternative to steroids after cataract extraction. PMID- 11777717 TI - Revisiting early postoperative follow-up after phacoemulsification. AB - PURPOSE: To determine whether postoperative evaluation of routine phacoemulsification can be safely and effectively performed on the day of surgery and 4 days postoperatively and evaluate the incidence and management of early intraocular pressure (IOP) elevations 3 to 7 hours postoperatively in patients with or without glaucoma. SETTING: Community-based hospital. METHODS: This retrospective series comprised 465 consecutive patients who had phacoemulsification and intraocular lens implantation. All patients had postoperative follow-up on the day of surgery (3 to 7 hours postoperatively) and at 4 days. Patients were classified into 2 groups: nonglaucoma (NG), 396 patients; and glaucoma (GL), 69 patients. The main outcome measures were the incidence and management of postoperative complications including IOP spikes, wound leaks, uveitis, and endophthalmitis. RESULTS: Three to 7 hours postoperatively, 73 NG (18.4%) and 32 GL (46.4%) patients had IOP elevations greater than 28 mm Hg, a significant change from baseline (P <.0001). Fourteen NG (3.6%) and 13 GL (18.8%) patients had IOP elevations greater than 40 mm Hg (P <.0001). Significant IOP elevations were effectively managed with a paracentesis with or without short-term antiglaucoma medications on the day of surgery, with 75 NG (18.9%) and 39 GL (56.5%) patients requiring IOP intervention. There were no IOP elevations greater than 21 mm Hg on the next day or at 4 days. There were no complications that were missed at the same-day evaluation that may have been identified at the 1-day postoperative visit. CONCLUSIONS: The results indicate that after routine phacoemulsification, patients can be safely and effectively reviewed on the day of surgery and 4 days postoperatively to identify and manage early postoperative IOP spikes. A significant number of patients, particularly those with preexisting glaucoma, had potentially harmful IOP spikes 3 to 7 hours postoperatively. PMID- 11777718 TI - Risk factors for contraction of the anterior capsule opening after cataract surgery. AB - PURPOSE: To investigate the factors contributing to contraction of the anterior capsule opening (ACO) after cataract surgery in normal eyes. SETTING: Department of Ophthalmology, University of Tokyo, School of Medicine, Tokyo, and Kaiya Eye Clinic, Hamamatsu, Japan. METHODS: This study included 141 eyes of 141 patients scheduled to have cataract surgery. The area of the ACO was determined by diaphanoscopy using the EAS-1000 anterior eye segment analysis system 1 day and 9 months postoperatively, after which the percentage reduction in the ACO area was calculated. Aqueous flare intensity was measured with a laser flare-cell meter 1 week and 9 months after surgery. Multiple regression analysis was performed to determine which factors were correlated with the percentage reduction in the ACO area. Variables tested included patient age, axial length, the ACO area on the first postoperative day, and flare values 1 week and 9 months after surgery. RESULTS: Patient age (r = 0.193, P =.029) and flare intensity 9 months after surgery (r = 0.255, P =.007) were significantly correlated with the percentage reduction in the ACO area (R(2) = 0.133). The axial length, ACO area 1 day postoperatively, and flare value at 1 week were not correlated with ACO contraction. CONCLUSION: Contraction of the ACO after cataract surgery is related to instability of the blood-aqueous barrier. PMID- 11777719 TI - Effect of Honan balloon compression on peribulbar anesthesia adequacy in cataract surgery. AB - PURPOSE: To ascertain whether a Honan balloon is necessary to produce effective peribulbar anesthesia in routine cataract surgery by evaluating its effect on intraocular pressure (IOP), surgeon assessment of the anesthesia's effectiveness, and patients' analgesic experience. SETTING: West of England Eye Unit, Royal Devon and Exeter Hospital, England. METHOD: Fifty eyes of 50 patients having routine phacoemulsification cataract extraction and intraocular lens implantation were randomized to have 10-minute ocular compression with the Honan balloon or no compression after peribulbar anesthesia. A single investigator gave all the peribulbar injections using a standard technique. The IOP was measured immediately before and 10 minutes after the injections. Two surgeons who were blinded to the randomization process performed the surgeries and completed an assessment questionnaire on various aspects of the peribulbar block. The patients also scored their level of analgesia during surgery. RESULTS: In the 26 patients who had Honan balloon compression, there was a significant reduction in IOP (mean 6.2 mm Hg; P <.05). In the 24 patients with no balloon compression, there were no significant changes in IOP 10 minutes after the peribulbar injections. There was no statistically significant difference in the surgeons' scores in any aspect of the peribulbar anesthesia (P >.05). All patients experienced a good level of analgesia. CONCLUSIONS: There was a significant reduction in IOP after Honan balloon ocular compression. However, there was no significant increase in IOP without balloon compression. The use of a Honan balloon did not appear to make a significant difference in the effectiveness of the peribulbar anesthesia to the surgeons or patients. PMID- 11777720 TI - Effect of incision size and site on corneal endothelial changes in cataract surgery. AB - PURPOSE: To compare endothelial damage induced by different cataract incision sites and sizes using specular microscopy. SETTING: Department of Ophthalmology, Hospital of San Dona di Piave, Venice, Italy. METHODS: Eighty-one eyes having phacoemulsification were randomly assigned to 1 of 3 groups of 27 eyes each: 3.5 mm clear corneal incision (CCI) with silicone foldable intraocular lens (IOL) implantation; 5.5 mm sutured CCI with poly(methyl methacrylate) (PMMA) IOL implantation; 5.5 mm scleral tunnel with PMMA IOL implantation. All incisions were centered at the 120-degree semimeridian; that is, they were superotemporal in right eyes and superonasal in left eyes. Noncontact specular microscopy was performed in the center and at the 12 o'clock position preoperatively as well as 1 week and 1, 3, and 12 months postoperatively. The endothelial cell density, mean cell area, cell size variation coefficient, percentage of hexagonality, and corneal thickness were considered. RESULTS: Progressive endothelial cell loss and an increase in mean cell area occurred in all groups during the follow-up. The cell loss percentages relative to the endothelial center appeared similar among the groups and slightly although not significantly lower in the scleral tunnel group. The scleral tunnel group had a statistically significant lower cell loss percentage at the 12 o'clock position than the 2 CCI groups at all follow-ups. CONCLUSIONS: The scleral tunnel group had less postoperative endothelial damage than the 2 CCI groups, with a statistically significant difference at the 12 o'clock position. This is probably because the scleral tunnel incision is placed more posteriorly and therefore induces less direct and indirect endothelial trauma. PMID- 11777721 TI - Intraoperative and early postoperative results of suction posterior capsulorhexis. AB - PURPOSE: To report the intraoperative complications and early postoperative visual results of suction posterior capsulorhexis (SPC). SETTING: Ophthalmology department of a district general hospital, Kent, United Kingdom. METHODS: This prospective observational study included all patients having phacoemulsification who required SPC as a planned procedure or because of posterior capsule tears (128 eyes of 122 patients). All patients were under the care of a single consultant. Intraoperative complications related to the SPC as well as postoperative complications and best corrected visual acuity (BCVA) in all cases and with best-case analysis (patients with preexisting ocular comorbidity excluded) were noted. RESULTS: Seven cases (5.5%) of vitreous prolapse occurred; none was specifically related to the SPC. A BCVA of 0.67 (6/9) or better was achieved in 94% of cases (100% of best cases). One retinal detachment (0.8%) occurred 8 months postoperatively that was successfully treated with no loss of BCVA. CONCLUSION: Suction posterior capsulorhexis had a low rate of intraoperative complications and did not adversely affect the early visual outcome. PMID- 11777722 TI - Accuracy of IRAS GT interferometer and potential acuity meter prediction of visual acuity after phacoemulsification: prospective comparative study. AB - PURPOSE: To assess and compare the accuracy of 2 methods of predicting visual acuity after phacoemulsification. SETTING: Department of Ophthalmology, Montpellier, France. METHODS: This prospective study evaluated 47 eyes of 47 patients having uneventful phacoemulsification over a 1-month period. All the patients had mild to moderate cataract. Visual acuity recovery was predicted using the white-light IRAS GT interferometer on the 3- and 8-degree wide test area and the Guyton-Minkowski potential acuity meter (PAM). Best corrected visual acuity was evaluated 1 day before and 1 month after surgery. RESULTS: Both the interferometer and PAM underestimated the retinal visual capacity. Three-degree white-light interferometry gave significantly better mean predicted results than 8-degree interferometry and the PAM. There was no statistically significant disparity between predicted and postoperative results with 3-degree interferometry (1.04 +/- 0.57 logMAR; -0.09 +/- 0.27 decimal) (P =.0647) and a statistically significant disparity with 8-degree interferometry (0.89 +/- 0.59 logMAR; -0.13 +/- 0.27 decimal) and the PAM (0.66 +/- 0.62 logMAR; -0.22 +/- 0.24 decimal) (P =.0001). The predicted values were widely dispersed; the correlation indices were 0.38 with the PAM (P =.091), 0.39 with 3-degree interferometry (P =.001), and 0.49 with 8-degree interferometry (P =.0005). CONCLUSIONS: Three degree white-light interferometry gave more accurate results than 8-degree interferometry and the PAM. The wide dispersion of results and unsatisfactory correlation indices show the tests are poor predictors of individual acuity. They should be used semiquantitatively and the results interpreted in relation to the clinical data. Qualitative methods may be useful in confirming or refuting visual recovery capacity ascertained by quantitative systems. PMID- 11777723 TI - Intracapsular ring sustained 5-fluorouracil delivery system for the prevention of posterior capsule opacification in rabbits: a histological study. AB - PURPOSE: To evaluate the efficacy of an intracapsular ring releasing 5 fluorouracil (5-FU) in preventing posterior capsule opacification (PCO) in rabbit eyes. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA, and Chu Morvan, Department d'Ophtalmologie, University of Brest, France. METHODS: Seventeen rabbits were divided into 3 groups: Group 1, 6 rabbits (6 eyes), had phacoemulsification only (control group); Group 2, 6 rabbits (6 eyes), had phacoemulsification with implantation of an open-loop hydrogel intracapsular ring; Group 3, 5 rabbits (5 eyes), had phacoemulsification with implantation of a ring with sustained release of 0.25 microg/h of 5-FU for 9 days. All eyes were followed for 8 weeks before enucleation. Capsular bag shrinkage and the position of the intracapsular ring were assessed, and central and peripheral PCO was evaluated for intensity and area by stereomicroscopy from a posterior (Miyake Apple) view. The residual equatorial lens epithelial cells (LECs) were counted by the same observer in histological sections. Transmission electron microscopy (TEM) of the cornea, capsular bag, and retina was done to evaluate the toxicity of 5-FU. RESULTS: No significant difference was seen in the degree of capsular bag shrinkage in the 3 groups. The intracapsular ring was decentered in 2 eyes (1 each in Groups 2 and 3). There was a statistically significant difference (P <.05, Student t test) between Group 1 and Groups 2 and 3 in the area and intensity of central PCO. There was no difference between Groups 2 and 3 in the intensity of central PCO. No evidence of 5-FU toxicity to intraocular structures (cornea, capsular bag, and retina) was demonstrated on TEM analysis. CONCLUSION: Implantation of an intracapsular ring may prevent central PCO after cataract surgery by mechanically blocking LEC migration toward the central visual axis. The potential pharmacological effect of 5-FU in PCO prevention was not demonstrated. PMID- 11777725 TI - International Intraocular Lens & Implant Registry 2002. AB - This article is the fourth annual update of the International Intraocular Lens & Implant Registry. A total of 1348 intraocular lenses or nonoptical implants from 34 manufacturers are available to surgeons in 2002. PMID- 11777724 TI - Effect of corneal wetting solutions on corneal thickness during ophthalmic surgery. AB - PURPOSE: To measure the changes in corneal thickness with wetting solutions used in ophthalmic surgery. SETTINGS: Ege University, School of Medicine, Department of Ophthalmology, Izmir, Turkey. METHODS: Thirty-one adult pigmented rabbits that weighed about 2.5 kg each were anesthetized with pentobarbital sodium. The rabbits were randomly divided into 3 groups to receive 3 wetting solutions: Group 1, Ringer's lactate; Group 2, balanced salt solution (BSS); and Group 3, BSS with glutation (BSS Plus). The solutions were dropped on the right cornea of the rabbits at a rate of 6.0 cc in 12 minutes using an intravenous infusion pump. Corneal thickness was measured by ultrasonic pachymetry before and after the procedure, and the between-group changes in corneal thickness were compared. RESULTS: The corneal thickness before and after the procedure was 361.27 microm +/- 19.3 (SD) and 380.00 +/- 25.0 microm, respectively, in Group 1 (P =.000); 372.10 +/- 18.8 microm and 388.60 +/- 24.1 microm, respectively, in Group 2 (P =.003); and 358.10 +/- 26.5 microm and 360.10 +/- 24.1 microm, respectively, in Group 3 (P =.316). CONCLUSION: As a corneal wetting solution, BSS Plus resulted in significantly fewer changes in corneal thickness than Ringer's lactate or BSS. This should be considered in cases involving long intraocular surgery. PMID- 11777726 TI - Postoperative management and follow-up after corneal flap loss following laser in situ keratomileusis. AB - We present 3 cases of flap loss within 2 weeks of unilateral laser in situ keratomileusis. In all patients, spontaneous regeneration of the epithelial layer, covering the ablated stroma, was expected. In 2 patients, the best spectacle-corrected visual acuity recovered to 20/25 within 6 months and in 1 patient, a contact lens was fitted 6 months after the accident, restoring visual acuity to 20/25. The 6-month follow-up and the contact lens fitting technique are described. PMID- 11777727 TI - Mystery of the vanishing iris. AB - We present the first reported case of traumatic aniridia as an isolated injury after blunt trauma to an eye that had phacoemulsification through a corneal tunnel. This case provides insight into the properties of the self-sealing corneal tunnel and possible advantages that it may confer on the eye. PMID- 11777728 TI - Suture fixation of a foldable acrylic intraocular lens for ectopia lentis. AB - A 5-year-old boy with severe ectopia lentis had bilateral lensectomy and suture fixation of a foldable acrylic intraocular lens (IOL) through a 3.0 mm clear corneal incision. Sodium hyaluronate (Healon GV) enhanced stability of the crystalline lens during aspiration and maintenance of the anterior chamber during passage of the needles through the ciliary sulcus. The haptic design of the single-piece AcrySof (Alcon) IOL permitted secure fixation of the suture to the haptic. The patient experienced rapid visual rehabilitation, achieving an uncorrected visual acuity of 20/40 in both eyes. PMID- 11777729 TI - Topography-guided excimer laser ablation of irregular cornea resulting from penetrating injury. AB - A 26-year-old woman with irregular astigmatism caused by ocular perforation became aphakic in the injured left eye 2 years after the initial trauma. The initial corneoscleral wound repair was performed without intraocular lens implantation. The patient's uncorrected visual acuity in the right eye was 20/20 and in the left eye, counting fingers at 50 cm. The vision in the left eye could not be corrected with a spectacle because of high corneal astigmatism so a rigid gas-permeable contact lens was tried. With a contact lens, the acuity improved to 20/80; however, the patient could not wear the lens because of intolerance and severe astigmatism. As an alternative, topography-guided ablation was performed to correct the corneal astigmatism. Treatment of the irregular central cornea reduced the astigmatism. Three months postoperatively, the corrected visual acuity was 20/20 with a refraction of +8.00 -1.50 x 26. This case indicates that topography-guided ablation can be a useful surgical method for correcting surgically induced irregular astigmatism. PMID- 11777730 TI - Phacoemulsification in spherophakia with corneal touch. AB - A phacoemulsification procedure with implantation of a foldable acrylic intraocular lens in a 31-year-old man with spherophakia is described. The procedure was necessitated by anterior dislocation of the spherophakic lens, with corneal endothelial contact and development of central corneal edema. With a careful approach, the procedure was uneventful and the outcome successful. Modern small-incision cataract surgery techniques are of great benefit in this type of complicated case. PMID- 11777731 TI - Inadvertent retrobulbar administration of hypertonic saline prior to cataract extraction. AB - A 36-year-old woman with retinitis pigmentosa was scheduled for removal of posterior subcapsular cataracts and experienced inadvertent retrobulbar administration of hypertonic saline. The patient developed retrobulbar pain and ophthalmoplegia that slowly improved over time. Hypertonic saline may cause ophthalmoplegia and pain if inadvertently given as a retrobulbar injection. PMID- 11777732 TI - Short-acting peribulbar anesthesia with 2-chloroprocaine. AB - A 64-year-old monocular man had uneventful penetrating keratoplasty in his seeing eye for aphakic bullous keratopathy and counting fingers visual acuity. One year later, standard slitlamp suture removal under topical anesthesia was not possible because of sensory nystagmus. In addition, the patient could not have general anesthesia as a consequence of severe coronary artery disease. He requested that the procedure be done with a short-acting local anesthetic agent so a patch would not be necessary. He successfully had the procedure using a peribulbar injection of 2-chloroprocaine (Nesacaine-MPF); vision and ocular motility returned 15 minutes after the surgery was completed. At subsequent examinations, the visual acuity was 20/200 and the graft was clear despite a congenital macular scar. PMID- 11777733 TI - Huntington's disease: a review of the literature on prevalence and treatment of neuropsychiatric phenomena. AB - A review was made of the literature on Huntington's disease, including the clinical neurology, recent advances in pathophysiology and genetic mechanisms and psychopathology. It can be concluded that research on the latter is scarce, although the subject is relevant because of the co-occurrence of psychiatric, neurological and genetic phenomena, which may lead to novel concepts in the understanding of brain function. So far, attempts to provide a comprehensive and pragmatic description of the psychopathology of Huntington's disease have been disappointing, probably due to the limitations of the DSM classification system in this disorder. Future research should focus not only on this classification system, but also on neuropsychological functioning, because of the degenerative nature of the disease. Systematic and controlled studies should be performed on the treatment of psychiatric abnormalities in Huntington's disease before any conclusions can be drawn. PMID- 11777734 TI - Efficacy of a psychoeducational intervention in improving relatives' knowledge about schizophrenia and reducing rehospitalisation. AB - We sought to establish if a brief psychoeducational intervention for relatives is effective in improving relatives' knowledge about schizophrenia and reducing rehospitalization. We evaluated 101 relatives of 55 patients with schizophrenia before and after an 8-week psychoeducational group using a self-report method. We also conducted a matched case-control study of the effects on rehospitalisation for 28 of these patients. We calculated the number of hospital days for each index case and control in the 1 and 2 years before and after the intervention. Relatives made significant gains in their knowledge about schizophrenia, particularly about medication. Patients whose relatives attended the group had significantly fewer days in hospital and days per admission compared to controls in the year after the programme but the effect waned in the second year after the intervention. Controls were almost four times more likely to be readmitted at 2 years than cases. Median time to readmission was significantly longer in cases compared to controls. We conclude that a psychoeducational group, which is valued by carers, is effective in increasing their knowledge about schizophrenia as well as reducing and forestalling the rehospitalization of their affected relatives. Such programmes deliver what carers frequently request in a cost-effective manner. PMID- 11777735 TI - Attitude towards psychiatric patients: a pilot study in a northern Italian town. AB - The stigmatisation of the psychiatric patient is still a strong barrier to the integration process of these subjects in our society. Therefore, it is necessary to identify what types of prejudices exist and the types of variables with which they are linked, in order to plan strategies to reduce them. In this exploratory study we administered a semi-structured interview to 303 subjects in order to examine the relationships between social attitudes towards mental disorders and some social demographic variables, the information about mental disorders and the previous 'contacts' with psychiatric patients. The data analysis shows that there is a relationship between knowledge of psychiatric patients and a more positive attitude towards them (i.e., less fear, more integration and work opportunities). This study is to be considered preliminary as far as people's attitudes towards psychiatric patients are concerned. This result encourages the planning and implementation of sensitisation and information programs concerning mental disorders, in the sense that increasing the knowledge of mental disorders could lead to significant achievements in the important fight against the stigma surrounding psychiatric patients. PMID- 11777736 TI - Violence and its prediction at a psychiatric hospital. AB - Aggressive behaviour in psychiatric inpatients was assessed before and after a training course for staff members. The Social Dysfunction Aggression Scale (SDAS) was used to report and assess aggressive behaviour over time, and the Staff Observation Aggression Scale (SOAS) to report and assess single aggressive incidents. In addition, the numbers of nursing staff members who were on sick leave because of injuries in the periods before and after the course were recorded and compared. No statistically significant reduction was found in the number of aggressive patients or in the number of staff members on sick leave. One interesting finding was a lower reporting on the SOAS of perceived aggressive incidents after the training course in comparison with the SDAS reports. Directed verbal aggressiveness and violence towards things were found to be predictors of violence. PMID- 11777737 TI - Nonresponder anorectic patients after 6 months of multimodal treatment: predictors of outcome. AB - Currently the therapy of anorexia nervosa is a relevant clinical problem. The percentage of patients who respond to short-term pharmacotherapy and psychotherapy is still low and the condition often leads to chronic pathology or death. The present study aims to determine outcome predictors beyond personality traits, eating psychopathology, or particular clinical features. Forty patients with restricter type anorexia nervosa were tested, at T0 and after 180 days, with psychometric tests and clinical evaluation instruments. Patients were then divided into two groups. One group included patients who showed relevant clinical improvement; the other included not-yet-improved patients. A lower Novelty Seeking, higher levels of Ascetism and Maturity Fears characterised the not-yet improved group. Correlation showed evidence of diverse bonds between personality and psychopathology in the improved and not-yet-improved groups. The psychopathology of non-yet-improved patients seemed to be more linked to their temperamental features, whereas improved patients seemed to be more influenced by their character. Different levels of psychological functioning can be expressed. The present data suggest focusing pharmacotherapy and psychotherapy, even family counseling, with a progression more strictly related to the current personality functioning level and psychopathology of each patient. PMID- 11777738 TI - Quality of life and treatment costs in schizophrenic outpatients, treated with depot neuroleptics. AB - Study aim was 1) to find out the influences on quality of life (QoL) of chronic outpatients with schizophrenia; 2) to calculate Quality Adjusted Life Years (QALY); and 3) to estimate direct 1-year treatment costs. In a 20% sample (100 males, 100 females) of schizophrenic outpatients from the Outpatients Clinic in Ljubljana, Slovenia receiving depot neuroleptics demographic, clinical, and treatment data were collected for the year 1996. The Krawiecka Scale, Global Assessment Scale (GAS), Abnormal Involuntary Movement Scale, Rating Scale for Drug-Induced Akathisia, Rating Scale for Extrapyramidal Side Effects, Quality of Life Scale (QLS), EQ-5D and QALY were used. Multivariate linear regression was used with the QLS score as dependent variable. The patients were on average 44 years old and had been treated for 14 years. The average GAS score was 70. GAS was positively related to the QLS score while the parkinsonism score was inversely correlated with QLS. The patients can expect to live for 10. 20 more QALY on average. The QoL on the EQ-5D scale was 0.73. The annual direct treatment costs amounted to $216,216 in 1996 prices. In well-adjusted chronic patients with schizophrenia the QoL seems to depend mostly on their psychosocial performance and side effects. Although rare, re-hospitalisations accounted for one-half of all treatment expenses. PMID- 11777739 TI - Criminal responsibility assessment in Switzerland: changes and continuity. AB - BACKGROUND: The factors that experts use to assess criminal responsibility are not very well known. Changes in the importance attributed to certain diagnoses are occasionally mentioned in the literature. The aim of this study is to identify the existence and the nature of such modifications. METHOD: We compared the socio-demographic, criminological and psychiatric characteristics of two samples of psychiatric assessments carried out in Geneva, Switzerland in 1973-74 (N = 75) and 1997-98 (N = 94). RESULTS: The two groups of subjects described by the experts' reports appear to be quite different in several characteristics. However, the rate at which experts conclude their reports in favour of diminished responsibility was not found to be significantly different. The logistic regression shows that the diagnosis of personality disorder is the only variable that influenced the experts differently for the 1997-98 period compared to the 1973-74 period. CONCLUSION: In Geneva, psychiatric experts still continue to ascribe diminished responsibility to offenders suffering from psychosis or depression. However, the population that undergoes psychiatric assessments nowadays has changed considerably. PMID- 11777740 TI - Has there been a decrease in the prevalence of mood disorders in HIV-seropositive individuals since the introduction of combination therapy? AB - PURPOSE: The aim of this study was to assess the prevalence of current mood disorders in HIV-seropositive patients treated with combined antiretroviral drug therapy including or not protease inhibitors. SUBJECTS AND METHODS: A random sample of 90 subjects consecutively attending, between February 1 and July 31, 1998, the outpatient unit of the Second Department of Infectious Diseases of the 'L. Sacco' Hospital in Milan was assessed by means of the Structured Clinical Interview for DSMIII-R (SCID) and the Zung Self-Rating Depression Scale (ZSDS). RESULTS: Twenty-three-point-three percent of the subjects were classified in CDC stage A, 32.3% in CDC stage B and 44.4% in CDC stage C. A DSMIII-R psychiatric diagnosis of current mood disorder was found in 4.4% of the recruited sample (dysthymia: 2.2%; adjustment disorder with depressed mood: 2.2%). CONCLUSIONS: Direct and indirect effect of new combination therapies, epidemiological changes in social groups affected by HIV and possible modifications in social perception of people with HIV infection may explain, at least in part, the decreased prevalence of current mood disorders observed in our study as compared to prevalence rates reported in the pre-HAART era. PMID- 11777741 TI - Association between severity of schizophrenic symptoms and urinary retention. AB - A case is presented in which severe urinary retention (UR) occurred during an acute psychotic exacerbation of paranoid schizophrenia. The voiding dysfunction was apparent during continuous treatment with unchanged doses of haloperidol, and it completely resolved with the remission of the psychotic symptoms. A clear temporal correlation was evident between the patient's mental status, the Brief Psychiatric Rating Scale (BPRS) score and the degree of the UR as assessed by quantitatively measuring the total daily post-voiding urine residues. We could not relate the UR to any apparent general medical condition or to the haloperidol treatment. The presented data suggests that UR in schizophrenic patients might be the end-result of various psychosis-related mechanisms. PMID- 11777742 TI - Simultaneous madness in twin sisters. PMID- 11777743 TI - First report of mirtazapine-induced arthralgia. AB - OBJECTIVE: The aim of our work is to describe the first two cases of arthralgia associated with the antidepressant drug mirtazapine. METHOD: Descriptive analysis of two iatrogenic cases. The review of the literature was achieved by the traditional electronic methods. The French database of iatrogenic cases was consulted. RESULTS: A 53-year-old man presented with gonalgia after some weeks of mirtazapine treatment. The intensity of the arthralgia was correlated with the dosage and the adverse effect rapidly disappeared after the antidepressant therapy was stopped. A 38-year-old woman received mirtazapine for 3 months and complained of arthralgia and myalgia. This clinical picture was suspended as the drug was stopped and a positive reintroduction was observed. No other cause was found in these two patients. DISCUSSION: No similar case has been reported in the international literature, but several observations of arthralgia with mianserin are mentioned. As mirtazapine is the 6-aza derivative of the tetracyclic antidepressant mianserin, the similarities of their chemical structures begs the responsibility of mirtazapine for arthralgia. PMID- 11777744 TI - Three challenges and a rechallenge episode of angio-oedema occurring in treatment with risperidone. PMID- 11777745 TI - Prevalence of MDMA (ecstasy) use and neurotoxicity. PMID- 11777746 TI - Handling of computational in vitro/in vivo correlation problems by Microsoft Excel: I. Principles and some general algorithms. AB - Most computations in the field of in vitro/in vivo correlations can be handled directly by Excel worksheets, without the need for specialized software. Following a summary of Excel features, applications are illustrated for numerical computation of AUC and Mean, Wagner-Nelson and Loo-Riegelman absorption plots, and polyexponential curve fitting. PMID- 11777747 TI - Typical variability and evaluation of sources of variability in drug dissolution testing. AB - To investigate variability in dissolution testing an international collaborative study was performed by 29 laboratories. Glibenclamide (glyburide) tablets were used in the investigation in which multipoint dissolution profiles were established using USP paddle apparatus. In contrast to a previous report, the variability of the glibenclamide dissolution data was significantly lower. Total variances (s(2)) were found to range from 18.34-44.18, Between Laboratory and Between Analyst variances (synthetic value) ranged from 12.9-38.7 and the Within Analyst variances ranged from 5.08-5.78. The dissolution profiles and corresponding variances obtained by laboratories with little or no experience in glibenclamide dissolution testing were similar to those obtained by more experienced laboratories, indicating that the test, especially when designed as multiple point dissolution testing, is sufficiently robust and capable of identifying differences in a manufacturing process or drug formulation. The smallest statistically detectable mean difference between two dissolution runs was calculated (95% CI) to be 7% for one analyst, or 5% if two analysts were to perform the dissolution tests. PMID- 11777748 TI - Post-iontophoresis recovery of human skin impedance in vivo. AB - The objective of this study was to better understand the recovery of human skin impedance following iontophoresis in vivo. Volunteers were subjected to a 15-min period of iontophoresis in the presence of aqueous solutions of either NaCl, KCl, CaCl(2) or MgCl(2) at 133 mM. Subsequently, the low-frequency impedance (at 1 Hz) recovery was followed for a further 30 min. Assuming direct proportionality between the reciprocal impedance and the ion concentration in the membrane, the experimental data were fitted to the appropriate solutions of Fick's second law of diffusion to derive characteristic diffusion parameters (D/L(2)), apparent diffusivities (D), diffusion pathlengths (L) and mobilities, and ion concentrations in the skin immediately post-iontophoresis. Ion fluxes out of the membrane after termination of current flow were also deduced. In general, recovery was relatively independent of the background electrolyte as previously reported, and the data were consistent with ion transport in predominantly aqueous pathways. Compared to its mobility in aqueous solution, however, the apparent Cl- mobility in the skin was smaller, presumably due to the fact that, under normal physiological conditions, the human skin barrier supports a net negative charge. In parallel, the initial "release" of Na+ and K+ from the skin post-iontophoresis was faster than that of Ca(2+) and Mg(2+), the latter cations of higher charge density being able to associate more strongly, it seems, with the negatively-charged skin. The simple physicochemical analysis of the data presented serves to emphasize that a decrease in skin impedance is not a manifestation of damage to the barrier--rather, it is a natural response to the relevant electrical potential and ion concentration gradients involved. PMID- 11777749 TI - Influence of Transcutol CG on the skin accumulation and transdermal permeation of ultraviolet absorbers. AB - The objective of this study was to determine the influence of Transcutol CG concentration on the transdermal permeation and skin accumulation of two ultraviolet (UV) absorbers, 2-hydroxy-4-methoxybenzophenone (oxybenzone) and 2 octyl-4-methoxycinnamate (cinnamate). The concentration of the UV absorber was held constant at 6% (w/w) for all vehicle systems while the concentration of Transcutol CG was varied from 0 to 50% (w/w). Data showed that both UV absorbers exhibited increases in skin accumulation with increasing concentrations of Transcutol CG. Skin accumulation of oxybenzone was significantly (P<0.05) greater than that of cinnamate for all formulations investigated. Oxybenzone skin accumulation ranged from 22.9+/-2.8 microg/mg (0% Transcutol CG) to 80.8+/-27.2 microg/mg (50% Transcutol CG). Cinnamate skin accumulation ranged from 9.0+/-0.9 microg/mg to 39.8+/-12.2 microg/mg at 0 and 50% Transcutol CG, respectively. No significant differences were found in the transdermal permeation of oxybenzone or cinnamate for any of the formulations tested. The results of this study demonstrate that the inclusion of Transcutol CG in sunscreen formulations increases the skin accumulation of the UV absorbers oxybenzone and cinnamate without a concomitant increase in transdermal permeation. PMID- 11777750 TI - Pharmacokinetics of verapamil and norverapamil from controlled release floating pellets in humans. AB - Pharmacokinetics of verapamil (V) in a dose of 40 mg and its metabolite norverapamil (N) from the new oral drug formulation in a form of capsule filled with floating pellets was determined. Conventional 40-mg tablets used in a medical practice served as a reference. Bioavailability studies were carried out in 12 healthy volunteers including six men and six women. In an in vitro test the pellets floated on the surface of the extraction fluid for 6 h. Mean value of maximum plasma concentration (C(max)) of V for floating pellets was 28.27 ng ml( 1) and t(max) 3.75 h. The value of the area under the concentrations versus time, AUC(0-infinity) was calculated as 364.65 ng ml(-1) h, biological half-lives of the absorption and elimination (t(0.5el)) phase were 0.5 h and 10.68 h, respectively. For the reference conventional tablets those values were 33.07 ng ml(-1), 1.21 h, 224.22 ng ml(-1) h, 0.36 h and 6.17 h, respectively. The average concentration of N in plasma was similar to that of V. PMID- 11777751 TI - Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility. AB - The role of gastrointestinal motility and pH in determining cimetidine bioavailability as well as double peaks in plasma profiles following oral administration, in the quiescent or active phase of antral motility, to humans in the fasted state was examined. Plasma cimetidine-time curves did not show the presence of double peaks in any subject following intravenous administration. The incidence of double peaks was 73% following oral administration and was independent of antral migrating motility complex phase. Further, it was found that oral administration of cimetidine in the quiescent phase resulted in significantly higher bioavailability and in other pharmacokinetic parameters compared to that obtained following administration in the active phase. Excellent linearity in plots of motility peaks vs. plasma peaks with slopes close to unity were evident for both quiescent (r(2)=0.93) and active phase (r(2)=0.97) administration. A total of 14 peaks out of 22 (10 subjects, 64%) and 20 out of 27 peaks (11 subjects, 74%), were accounted for in quiescent and active phase oral administration, respectively. The proximal occurrence of plasma peaks to antral motility peaks typical of phase III contractions strongly implies that motility patterns may be responsible for secondary maxima following oral cimetidine administration in the fasted state. PMID- 11777752 TI - Pharmacokinetic profile of a new controlled-release isosorbide-5-mononitrate 60 mg scored tablet (Monoket Multitab). AB - The influences of food, tablet splitting, and fractional dosing on the pharmacokinetics of a new controlled-release double-scored tablet containing 60 mg isosorbide-5-mononitrate (Monoket Multitab) were investigated in healthy male volunteers. Food interaction was evaluated after single dose administration under fasted conditions and after a standard high-fat breakfast. The effect of tablet splitting was assessed at steady-state, after 5 days of once daily dosing with the tablet taken intact or trisected. The influence of fractional dosing was assessed after 1 and 6 days of daily regimen of 40 mg in the morning (2/3 of a tablet) and 20 mg in the evening (1/3 of a tablet). The pharmacokinetics of isosorbide-5-mononitrate after taking the tablet intact or in three fragments were very similar with a mere 10% increase of maximum plasma concentration (C(max)) for the latter, while the time to peak (T(max)) decreased from 5 to 4 h and areas under the concentration vs. time curves (AUCs) were virtually unchanged. Morning trough concentration reached 53 and 46 ng/ml, respectively. Administration of the intact tablet after a high-fat breakfast increased C(max) by 18% and AUC by 21%, and slightly delayed T(max) from 5 to 6h. During fractional dosing, morning and evening C(max) reached 364 and 315 ng/ml on the first day, and 373 and 300 ng/ml on the 6th day, respectively. The ratio of AUC(0 24 h) on the last day to AUC(infinity) on the first day, was 82.1% (confidence limits 71.7-94.1%) possibly resulting from peripheral volume expansion. The release characteristics of Monoket Multitab are thus moderately influenced by concomitant intake of food and to a very minor extent by tablet breaking. Fractional dosing allows to achieve lower peak and higher morning trough levels, while total exposure is comparable to that during once daily dosing (AUC(0-24 h, s.s.) of 5.55+/-1.78 and 5.71+/-1.08 microg h/ml). PMID- 11777753 TI - In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer. AB - The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37 degrees C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0+/-2.7 (mean+/-S.D.) microg Gd/10(6) cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1+/-2.9 and 59.8+/-9.8 microg Gd/10(6) cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100-200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd DTPA, was suggested from transmission electron microscopy and comparative studies at 4 degrees C and with the solution system. These findings indicated that Gd nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported. PMID- 11777754 TI - In vitro evaluation of pectin-HPMC compression coated 5-aminosalicylic acid tablets for colonic delivery. AB - In this study, we report pectin-HPMC compression coated core tablets of 5 aminosalicylic acid (5-ASA) for colonic delivery. Each 100 mg core tablet contained 5-ASA and was compression coated at 20 kN or 30 kN using 100% pectin, 80% pectin-20% HPMC, or 60% pectin-40% HPMC, at two different coat weights as 400 or 500 mg. Drug dissolution/system erosion/degradation studies were carried out in pH 1.2 and 6.8 buffers using a pectinolytic enzyme. The system was designed based on the gastrointestinal transit time concept, under the assumption of colon arrival times of 6 h. It was found that pectin alone was not sufficient to protect the core tablets and HPMC addition was required to control the solubility of pectin. The optimum HPMC concentration was 20% and such system would protect the cores up to 6 h that corresponded to 25-35% erosion and after that under the influence of pectinase the system would degrade faster and delivering 5-ASA to the colon. The pectin-HPMC envelope was found to be a promising drug delivery system for those drugs to be delivered to the colon. PMID- 11777755 TI - Crystal forms of torasemide: new insights. AB - Crystallization from various organic solvents results in three crystal forms of torasemide: monotropically related mod. I (melting point, 158-161 degrees C) and mod. II (melting point, 155-158 degrees C), as well as a pseudopolymorphic crystal form (form A, channel inclusion compound with 1.9-4.2% water and alcohol). Physicochemical properties were determined by thermoanalysis (hot-stage microscopy, differential scanning calorimetry, thermogravimetry), Fourier transform infra-red and Raman spectroscopy, and X-ray powder diffractometry. The hygroscopicity, relative stability, true density, and heat of solutions were determined, respectively. The dissolution behaviour of mod. I and II was investigated as a function of pH, temperature, and in addition to surfactants. Mod. II is nearly three times more soluble than mod. I (mod. I, 0.34 mmol l(-1); mod. II, 0.93 mmol l(-1) at 20 degrees C, pH 4.90) and proved to be highly kinetically stable. By crystallization from 1-butanol, a new compound was synthesized, which was identified as [[4-[(3-Methylphenyl)amino]-3 pyridinyl]sulfonyl]-carbamic acid, butyl ester (TOBC). The most important properties of this torasemide derivative are given. The present results give a thorough physicochemical characterization of the crystal forms of torasemide. They clearly indicate a mistaken identity of mod. II with crystal form A in formerly published articles. PMID- 11777756 TI - Water transport and drug release study from cross-linked polyacrylamide grafted guar gum hydrogel microspheres for the controlled release application. AB - The graft copolymer (pAAm-g-GG) of guar gum with acrylamide was prepared and cross-linked with glutaraldehyde to form the hydrogel microspheres by the water in-oil (w/o) emulsification method. The microspheres were loaded with two antihypertensive drugs, verapamil hydrochloride (water-soluble) and nifedipine (water-insoluble) to investigate their controlled release characteristics. The drugs were incorporated either during cross-linking by dissolving it in the reaction medium or after cross-linking by the soaking technique. The microspheres were characterized by Fourier transform infrared spectroscopy, thermogravimetry, differential scanning calorimetry, equilibrium water uptake and dynamic swelling. The microspheres are spherical with smooth surfaces. Dynamic swelling experiments indicated that with an increase in cross-linking, water transport deviates from Fickian to non-Fickian mechanism. The in vitro drug release showed a dependence on the extent of cross-linking, amount of drug loading, nature of drug molecule and method of drug loading. Even though the release of drugs is swelling controlled in the initial stages, in the later stage diffusion of the solute is dominating. Various transport parameters have been calculated and the results are discussed in terms of the nature of the drug and the polymer. PMID- 11777757 TI - Self-adhesive thin films for topical delivery of 5-aminolevulinic acid. AB - Self-adhesive thin-films have been developed as a topical delivery system for 5 aminolevulinic acid (ALA). The thin films are suitable for use during the photodynamic therapy of epithelial skin tumors. They are composed of a combination of the lipophilic polymer Eudragit NE and the lipophilic plasticiser acetyl tributyl citrate (ATBC). Because of its hydrophilicity, ALA forms suspension systems within these thin films, as evidenced by light microscopy. ALA release measured using Franz cells is very rapid from a Eudragit NE thin film loaded with 10% w/w ALA (200 microg ALA after 2.5 h), and even higher when ATBC is included. A Eudragit NE/ATBC (1: 2) thin film loaded with 20% w/w ALA releases 2000 microg ALA after 3.5 h. Combined release/permeation of ALA through excised membranes of human stratum corneum plus epidermis yielded fluxes of 50-100 microg ALA within 5 h for the Eudragit NE/ATBC (1: 2) thin film. The ATBC acts as a permeation enhancer for ALA. Scanning electron microscopy of the thin film surface shows protruding ALA particles which rapidly dissolve on contact with an aqueous medium. This surface dissolution mechanism is the cause of the rapid ALA release and hence also the high skin permeation in vitro. The mechanical properties of the thin films were also briefly examined. Adhesive strength increases with higher ATBC loading and decreases with higher ALA loading. Internal cohesion decreases with greater ATBC loading and increases with higher ALA loading. As part of this project, an improved derivatisation assay for gradient HPLC of ALA with 9Fluorenylmethyloxycarbonylchloride is also presented. PMID- 11777758 TI - Marine sponge collagen: isolation, characterization and effects on the skin parameters surface-pH, moisture and sebum. AB - A previously described isolation procedure for collagen of the marine sponge Chondrosia reniformis Nardo was modified for scaling-up reasons yielding 30% of collagen (freeze-dried collagen in relation to freeze-dried sponge). Light microscope observations showed fibrous structures. Transmission electron microscopy studies proved the collagenous nature of this material: high magnifications showed the typical periodic banding-pattern of collagen fibres. However, the results of the amino acid analysis differed from most publications, presumably due to impurities that still were present. In agreement with earlier studies, sponge collagen was insoluble in dilute acid mediums and all solvents investigated. Dispersion of collagen was facilitated when dilute basic mediums were employed. The acid-base properties of the material were investigated by titration. Furthermore, a sponge extract was incorporated in two different formulations and compared with their extract-free analogues and a commercially available collagen containing product with respect to their effects on biophysical skin parameters. None of the preparations had a noticeable influence on the physiological skin surface pH. Skin hydration increased only slightly. However, all tested formulations showed a significant increase of lipids measured by sebumetry. PMID- 11777759 TI - A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. AB - The antimicrobial activity of chitosan in lipid emulsions as well as in aqueous solutions was investigated. Two types of long-chained chitosan were used differing in the molecular weights, degree of the deacetylation and their viscosity: type I, mol. weight 8.7 x 10(4) g/mol, 92% degree of deacetylation and a viscosity of 14 mPa s, type II, mol. weight of 5.32 x 10(5) g/mol, 73% degree of deacetylation and a viscosity of 461 mPa s. In order to assess the pH optimum of the antimicrobial activity of the biopolymer, suspensions of the microorganisms Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus niger were incubated at different pH-values in lactic acid solution (1% w/v) containing different concentrations of chitosan up to 1.5% (w/v). Emulsion formulations containing either 0.25%, 0.5% or no chitosan, respectively, were inoculated with the same microorganisms and were incubated at 25 degrees C. The aqueous solutions as well as the emulsions were examined for microbial counts on agar plates after different periods of incubation. After 24 h of incubation in aqueous solutions only the cfu numbers of the bacteria were reduced. Both types of chitosan revealed a pH optimum of their antibacterial activity at pH 5.0-5.1 for P. aeruginosa, and at pH 5.3 for S. aureus. In addition, chitosan with a mol. weight of 8.7 x 10(4) g/mol, high degree of deacetylation and low viscosity showed a higher antimicrobial activity than the other chitosan type of this study. It was found that lipid emulsions containing 0.5% chitosan (type I) conformed to the requirements of the preservation efficacy test for topical formulations according to the European Pharmacopoeia while the emulsion without chitosan and a lactic acid solution with and without the biopolymer did not conform. In hemolysis studies on human erythrocytes, the hemolytic activity of the lipid emulsions with chitosan was assessed. These emulsions showed a negligible hemolytic behavior. The results indicate a use of chitosan as antimicrobial preservative in emulsion formulations for mucosal as well for parenteral applications. PMID- 11777760 TI - Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form. AB - The aim of this research was to use a ram extruder to prepare directly a fast release dosage form with uniform shape and density, containing carbamazepine (C) as a water-insoluble drug and polyethylene glycol 4000 (PEG) as a low melting binder. The potential inclusion of lactose (L) as a hydrophilic filler was also considered. The temperature suitable to ensure a successful extrusion process of several formulations containing PEG in different percentages was found to be below the melting point of the PEG. The influence of composition on the extrusion process of different ram speeds was checked by measuring the pressure at the steady state, the apparent shear rate and the apparent shear stress of a range of mixtures of drug, lactose and PEG. The physical-mechanical properties of extrudates, including tensile strength and Young's modulus, prepared with different ram velocities were also determined. The solid-state physical structure by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) was established. The dissolution of the extrudates and their corresponding physical mixtures were compared. The mixtures were found to be shear thinning when extruded; the tensile strength of extrudates was dependent on the composition but not the extrusion rate, while the value of Young's modulus was strongly influenced by the rate of extrusion, but less affected by the composition of the extrudates. The results of DSC and XRD indicated that the solid structure of the extrudates corresponded to that of a physical mixture of the components, hence there had been no change in the physical form of the drug induced by extrusion. In terms of dissolution, the rate of the extrusion process did not influence the performance of the products, whereas the composition did. The extruded mixtures of an equivalent composition exhibited a more rapid release than a simple physical mixture. The addition of lactose reduced the dissolution rate. PMID- 11777763 TI - Clinical governance: is it coming of age? PMID- 11777764 TI - Real-time CT and CT fluoroscopy. PMID- 11777765 TI - Catheter angiography and angioplasty in patients with scleroderma. AB - The objectives of this study were (i) to identify patterns of angiographic disease in scleroderma patients with and without other vascular risk factors and (ii) to define patients with scleroderma in whom angiography and angioplasty is useful. The records of 26 patients with scleroderma who underwent angiography and angioplasty over an 8-year period were reviewed. Angiographic disease patterns were assessed using a modified Brewster classification. Angiography of the upper limb demonstrated distal disease alone in 86% of patients, both with and without other vascular risk factors such as smoking. In the lower limb there was a highly significant association between the presence of other vascular risk factors and macrovascular disease potentially amenable to angioplasty, and conversely between the absence of other vascular risk factors and distal disease in the lower limb. Good early but poor late clinical results were achieved in three of five patients who underwent angioplasty. Angiography of the upper limb is likely to demonstrate distal disease alone, and angiography and angioplasty of the lower limb may be useful only if other vascular risk factors are present. PMID- 11777766 TI - Stabilization of the hydrophilic sphere of non-ionic monomers: are all protected in a similar way? AB - The present study attempts to investigate whether incorporation of a methyl group as second substituent in the tertiary amido group of the two benzamide side chains of iobitridol (Xenetix) increases the stability of the hydrophilic sphere around this molecule as claimed by its manufacturer, and whether this hydrophilic sphere is unique to this particular molecule or to what extent other monomer non ionic contrast media show this feature. Five non-ionic monomer contrast medium molecules, ioversol, iohexol, iobitridol, ioxilan and iopromide, were studied. Barriers to the rotation of acetanilide and benzamide side chains, and to the rotation of the amide bond in the benzamide chains, were calculated at a semi empirical quantum mechanical level of theory with the Mopac/Ampac computer program. The five studied contrast medium molecules showed very similar energy barriers to the rotation of complete substituent chains (benzamide and acetanilide) around their bond with the benzene ring. The magnitude of the barriers fell in the range of values mentioned in the literature. In conclusion, introduction of a methyl group as second substituent in the tertiary amido group of the benzamide substituent chains of iobitridol does not increase the studied rotation barriers, i.e. it does not seem to stabilize the hydrophilic sphere to a greater extent compared with similar monomer non-ionic molecules. The sphere is shown to exist in all five analysed molecules. Introduction of a group with a more hydrophobic character has to be considered and eventually questioned, bearing in mind that a more hydrophilic molecule interacts to a lesser degree with body systems. PMID- 11777767 TI - Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers. AB - Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/ 8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation. PMID- 11777768 TI - Effects of radiographic contrast media on pulmonary vascular resistance of normoxic and chronically hypoxic pulmonary hypertensive rats. AB - Intravascular radiographic contrast media (RCM) can be associated with significant morbidity in patients with pulmonary hypertension (PH). This study investigated the direct effect of the four main classes of RCM (high osmolar ionic monomer "diatrizoate"; low osmolar ionic dimer "ioxaglate"; low osmolar non ionic monomer "iopromide"; and iso-osmolar non-ionic dimer "iotrolan") in ex vivo isolated rat lungs perfused with blood at 20 ml min(-1) under basal conditions (air + 5% CO2 ventilation, pulmonary artery pressure (Ppa) 16-20 mmHg) and when Ppa was raised by hypoxic vasoconstriction in normal rats (2-3% O2+5% CO2 ventilation, Ppa increased by 4-14 mmHg). The effects of low osmolar RCM (ioxaglate, iopromide and iotrolan) were also studied in rats with PH induced by chronic hypoxia (3 weeks 10% O2, Ppa 26-36 mmHg). Increasing volumes (0.05 ml, 0.1 ml, 0.3 ml, and 0.5 ml) of RCM, mannitol (osmolar and pH control) or normal saline (volume control) were added to the 10 ml blood reservoir (n=4-9 per group). In normal rats, RCM caused a dose-dependent slow rise in Ppa. The maximum rise in mean+/-SEM Ppa at the cumulative dose of 0.95 ml was ioxaglate 13.8+/-1.6 mmHg>iotrolan 7.3+/-1.7 mmHg=diatrizoate 9.8+/-2.2 mmHg>iopromide 3.0+/-0.8 mmHg (p<0.05). The rise in Ppa induced by ioxaglate and iotrolan was significantly greater than in the mannitol and saline controls (p<0.05). Pre-treatment with endothelin receptor A/B blockade (SB209670) did not abolish the rise in Ppa induced by diatrizoate (0.95 ml) in the normal rat (3.8+/-1.3 mmHg diatrizoate alone and 3.4+/-1.1 mmHg in the presence of 40 microM SB209670, n=5 per group). When Ppa was raised by acute hypoxia, ioxaglate and diatrizoate (0.5 ml) caused a fall in Ppa (percentage fall -53+/-23 and -118+/-10, respectively, p<0.001) while iotrolan and iopromide caused a small further rise in Ppa, which was significant with iotrolan at a dose of 0.3 ml (percentage rise in pressure 14.2+/-2.3, p<0.05). In chronic pulmonary hypertensive rats, RCM (0.95 ml) caused an overall slow progressive rise in Ppa (iopromide 6.8+/-1.7 mmHg< ioxaglate 11.6+/-2.5 mmHg=iotrolan 12.7+/-1.1 mmHg). However, ioxaglate initially induced an acute fall of Ppa (maximum fall 4.22+/-0.9 mmHg, p<0.05) for almost 20 min. In summary, iopromide induced the least change in Ppa of normal and pulmonary hypertensive rats. The pathophysiology of the effects of RCM on the pulmonary circulation remains uncertain. PMID- 11777769 TI - A national survey of attitudes towards the use of MRI in patients known to have intracranial aneurysm clips. AB - The objective of this study was to determine the attitudes and practice of neuroradiology centres across the UK regarding the use of MRI in patients known to have intracranial aneurysm clips. A postal survey comprising three questions and a comments section was sent to 35 neuroradiology centres across the UK. There were 32 (91%) respondents to the single questionnaire. 16 (50%) respondents said that they would not consider performing MRI on a patient with an intracranial aneurysm clip. Of the remaining 50%, all said that identification of the clip type and assurance of its safety would be needed prior to scanning the patient. The magnetic strength of the system did not appear to affect the decision regarding whether or not to perform MRI on such patients. There was a variation in attitude towards the use of MRI in such patients between different regions. Neuroradiology centres are equally divided in their attitude and practice about whether it is safe to use MR to image a patient known to have an intracranial aneurysm clip. This is most probably due to the conflicting literature, as well as uncertainty about the identification and ferromagnetic properties of individual clips. PMID- 11777770 TI - Cancers detected and induced, and associated risk and benefit, in a breast screening programme. AB - Current cancer detection rates and dose levels in the UK Breast Screening Programme are used to compare numbers of cancers detected with numbers predicted to be induced by the screening process itself. Numbers of those detected are shown to exceed those induced by a large margin for women aged over 50 years. The associated benefit/risk ratio is also considered. For younger women this margin is progressively reduced but remains positive at least down to age 40 years, and possibly beyond. Women both with and without a family history of breast cancer are considered. Some implications for familial breast screening programmes are discussed. Some caution may be required before annual screening of women below the age of 35 years. PMID- 11777771 TI - Analysis of surface dose variation in CT procedures. AB - An experimental and theoretical study has been made of the variations in air kerma-length product (AKLP) at the surface of a phantom exposed in a CT scanner, using clinical parameters. For the theoretical part, a computer simulation was developed, based on a simple analytical model, requiring information generic to the scanner model. The effects of patient size, position within the gantry plane and beam-shaping filter type were studied using three different elliptical phantoms. A dose reduction technique based on a sinusoidal tube current modulation system was also investigated. The surface AKLP was shown to be independent of phantom size (within experimental error) but decreases as the surface moves vertically away from the isocentre. The major contributor to this variation is the beam-shaping filter. A maximum difference of 19% between the values of surface AKLP was calculated for the two beam-shaping filters available. When the tube current modulation system was used, the maximum surface dose reduction was 18%. A maximum difference of 2% was found between measurements and computer simulations. It is therefore possible to predict the behaviour of AKLP using the analytical model. As the dose measured on the surface of a patient is simply related to AKLP, the model can be applied to data obtained from patient surface dose surveys and can be helpful in interpreting the sources of variation in the latter. PMID- 11777772 TI - Bone densitometry in the management of Colles' fractures: which site to measure? AB - This study assessed whether patients with Colles' fractures can be evaluated by measurement of peripheral bone mineral density (BMD) instead of the more established axial BMD technique. 205 consecutive patients who had sustained a recent Colles' fracture were invited to attend for BMD measurement at the lumbar spine, hip and forearm by dual energy X-ray absorptiometry (DXA) using a Hologic QDR4500C instrument. Hologic normal reference ranges were used for spine and ultradistal radius BMD, and the NHANES 111 reference range was used for the femoral neck. 158 patients attended, of whom only 61 had a T-score below -2.5 at one of the three measured sites (84 T<-2.0, 112 T<-1.5). 36 patients had bilateral forearm fractures and did not undergo a forearm measurement. After excluding these patients and using a T-score of -2.5 as a diagnostic threshold, a spine and hip measurement strategy missed 26% of osteoporotic patients and a forearm only strategy missed 33%. If a forearm strategy is adopted, with axial BMD performed only on those patients with an ultradistal radial T-score of <-1.5 and >-2.5, 27 further scans would be required and only four patients with T<-2.5 at the spine or hip would be undetected. Where axial BMD measurement is performed, this should be accompanied by forearm BMD measurement in some patients with Colles' fractures. A peripheral bone mineral densitometry strategy using forearm BMD alone will miss many individuals with osteoporosis. Therefore where forearm, and probably any peripheral scanning method, only is used for patient assessment there should be close liaison with an axial BMD centre with agreed joint protocols, as some patients should be advised to have an additional axial BMD measurement following their peripheral BMD measurement. PMID- 11777773 TI - Stromal tumour within a Meckel's diverticulum: CT and ultrasound findings. AB - The incidence of tumours within a Meckel's diverticulum is 0.5-3.2%. Their pre operative diagnosis is rare. We report a case of an incidentally found gastrointestinal stromal tumour within a Meckel's diverticulum in a patient presenting with acute appendicitis. The tumour was demonstrated pre-operatively by ultrasound and CT. PMID- 11777774 TI - Disseminated aspergillosis inciting intestinal ischaemia and obstruction. AB - Invasive aspergillosis is an opportunistic infection that characteristically affects the immunocompromised host, resulting in a high degree of morbidity and mortality. Although the portal of entry is usually pulmonary, there are rare reports of invasive aspergillosis localized to the gastrointestinal tract. In addition, haematological spread may develop, with life threatening disseminated infection involving the vital organs and the gastrointestinal tract. Although disseminated infection is well recognized, the CT findings of gastrointestinal disease have not been reported to our knowledge. We describe the CT findings in a patient with invasive aspergillosis involving the gastrointestinal tract, which resulted in intestinal ischaemia complicated by small bowel obstruction. PMID- 11777775 TI - Ruptured mediastinal cystic teratoma with intrapulmonary bronchial invasion: CT demonstration. AB - Ruptured cystic mediastinal teratoma is rare. The diagnosis of this condition and a clear demonstration of its associated complications are important for defining the surgical approach. We report the CT findings of a case of mediastinal cystic teratoma before and after rupture. CT features of bursting of the spherical fatty compound and intrapulmonary bronchial invasion have not been previously described. PMID- 11777776 TI - Imaging the post-operative thoracic aorta: normal anatomy and pitfalls. AB - Following surgical repair or replacement of the thoracic aorta, interpretation of CT and MRI scans of the thorax can be confusing. It is important to be aware of the variety of appearances that can be encountered. There is usually a surgical explanation and close collaboration with surgical colleagues is required. An appreciation of the normal post-operative appearances allows recognition of the abnormal. Potential pitfalls in interpretation are discussed. PMID- 11777777 TI - A distinctive shoulder mass. PMID- 11777778 TI - Whole body radiation dose to the operator in bone mineral densitometry. PMID- 11777779 TI - Vesicoureteric reflux in Chinese children. PMID- 11777781 TI - Income inequality and population health. PMID- 11777782 TI - Comparing percutaneous tracheostomy with open surgical tracheostomy. PMID- 11777783 TI - Screening for inherited metabolic disease in newborn infants using tandem mass spectrometry. PMID- 11777784 TI - The BMJ: moving on. PMID- 11777785 TI - Chronic fatigue report delayed as row breaks out over content. PMID- 11777786 TI - WHO calls for new pact on health care. PMID- 11777789 TI - Adverse reactions to drugs increase. PMID- 11777790 TI - WHO calls for closer monitoring of commercial interests. PMID- 11777791 TI - Surgeon cleared of manslaughter. PMID- 11777792 TI - Drugs company makes false claims over bedwetting drug. PMID- 11777793 TI - Pay award a step in the right direction. PMID- 11777794 TI - Scots tackle racism in health service. PMID- 11777795 TI - R.E.S.P.E.C.T.-why doctors are still getting enough of it. PMID- 11777796 TI - Creating a healthy global economy. PMID- 11777797 TI - Income inequality, individual income, and mortality in Danish adults: analysis of pooled data from two cohort studies. AB - OBJECTIVE: To analyse the association between area income inequality and mortality after adjustment for individual income and other established risk factors. DESIGN: Analysis of pooled data from two cohort studies. The relation between income inequality in small areas of residence (parishes) and individual mortality was examined with Cox proportional hazard analyses. SETTING: Two population studies conducted in Copenhagen, Denmark. PARTICIPANTS: 13 710 women and 12 018 men followed for a mean of 12.8 years. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: Age standardised mortality was highest in the parishes with the least equal income distribution. After adjustment for individual risk factors, parish income inequality was not associated with mortality, whereas individual household income was. Thus, individuals in the highest income quarter had lower mortality than those in the lowest quarter (adjusted hazard ratio for men 0.51 (95% confidence interval 0.45 to 0.59) and for women 0.60 (0.54 to 0.68)). CONCLUSION: Area income inequality is not in itself associated with all cause mortality in this Danish population. Adjustment for individual risk factors makes the apparent effect disappear. This may be the result of Denmark's welfare system, based on a Nordic model. PMID- 11777798 TI - Individual income, income distribution, and self rated health in Japan: cross sectional analysis of nationally representative sample. AB - OBJECTIVE: To assess the effects on self rated health of individual income and income distribution in Japan. DESIGN: Cross sectional analysis. Data collected on household income, self rated health, and other sociodemographic characteristics at the individual level from comprehensive survey of the living conditions of people on health and welfare in a nationally representative sample from each prefecture. SETTING: Prefectures in Japan. PARTICIPANTS: 80 899 people aged >15 years with full records in survey. MAIN OUTCOME MEASURES: Dichotomous variable for self rated health of each respondent (0 if excellent, very good or good; 1 if fair or poor). RESULTS: Inequality in income at the prefecture level measured by the Gini coefficient was comparable with that in other industrialised countries. Unadjusted odds ratios show a 14% increased risk (odds ratio 1.14, 95% confidence interval 1.02 to 1.27) in reporting poor or fair health for individuals living in prefectures with higher inequality in income. After adjustment, individual income was more strongly associated with self rated health than income inequality. Additional inclusion of regional effects showed that median income at the prefecture level was inversely related to self rated health. CONCLUSIONS: Individual income, probably relative to the median prefecture income, has a stronger association with self rated health than income inequality at the prefecture level. PMID- 11777799 TI - Relations of income inequality and family income to chronic medical conditions and mental health disorders: national survey. AB - OBJECTIVES: To analyse the relation between geographical inequalities in income and the prevalence of common chronic medical conditions and mental health disorders, and to compare it with the relation between family income and these health problems. DESIGN: Nationally representative household telephone survey conducted in 1997-8. SETTING: 60 metropolitan areas or economic areas of the United States. PARTICIPANTS: 9585 adults who participated in the community tracking study. MAIN OUTCOME MEASURES: Self report of 17 common chronic medical conditions; current depressive disorder or anxiety disorder assessed by clinical screeners. RESULTS: A strong continuous association was seen between health and education or family income. No relation was found between income inequality and the prevalence of chronic medical problems or depressive disorders and anxiety disorders, either across the whole population or among poorer people. Only self reported overall health, the measure used in previous studies, was significantly correlated with inequality at the population level, but this correlation disappeared after adjustment for individual characteristics. CONCLUSIONS: This study provides no evidence for the hypothesis that income inequality is a major risk factor for common disorders of physical or mental health. PMID- 11777800 TI - Education, income inequality, and mortality: a multiple regression analysis. AB - OBJECTIVE: To test whether the relation between income inequality and mortality found in US states is because of different levels of formal education. DESIGN: Cross sectional, multiple regression analysis. SETTING: All US states and the District of Columbia (n=51). DATA SOURCES: US census statistics and vital statistics for the years 1989 and 1990. MAIN OUTCOME MEASURE: Multiple regression analysis with age adjusted mortality from all causes as the dependent variable and 3 independent variables-the Gini coefficient, per capita income, and percentage of people aged >/=18 years without a high school diploma. RESULTS: The income inequality effect disappeared when percentage of people without a high school diploma was added to the regression models. The fit of the regression significantly improved when education was added to the model. CONCLUSIONS: Lack of high school education accounts for the income inequality effect and is a powerful predictor of mortality variation among US states. PMID- 11777801 TI - Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort. PMID- 11777802 TI - Drug points: Ticlopidine associated with acute arthritis. PMID- 11777803 TI - Effect of beta lactam antibiotic use in children on pneumococcal resistance to penicillin: prospective cohort study. AB - OBJECTIVE: To examine the relation between use of antibiotics in a cohort of preschool children and nasal carriage of resistant strains of pneumococcus. DESIGN AND PARTICIPANTS: Prospective cohort study over two years of 461 children aged under 4 years living in Canberra, Australia. MAIN OUTCOME MEASURES: Use of drugs, respiratory symptoms, and visits to doctors were documented in a daily diary by parents of the children during 25 months of observation. Isolates of pneumococci, which were cultured from nasal swabs collected approximately six monthly, were tested for antibiotic resistance. RESULTS: From the four swab collections 631 positive pneumococcal isolates from 461 children were found, of which 13.6% were resistant to penicillin. Presence of penicillin resistant pneumococci was significantly associated with children's use of a beta lactam antibiotic in the two months before each swab collection (odds ratio 2.03 (95% confidence interval 1.15 to 3.56, P=0.01)). The odds ratio of the association remained >1 (though did not reach significance at the 0.05 level) for use in the six months before swab collection. The association was seen in children who received only penicillin or only cephalosporin antibiotics in that period. The odds ratio was 4.67 (1.29 to 17.09, P=0.02) in children who had received both types of beta lactam in the two months before their nasal swab. The modelled odds of carrying penicillin resistant pneumococcus was 4% higher for each additional day of use of beta lactam antibiotics in the six months before swab collection. CONCLUSIONS: Reduction in beta lactam use could quickly reduce the carriage rates of penicillin resistant pneumococci in early childhood. In view of the propensity of these organisms to be spread among children in the community, the prevalence of penicillin resistant organisms may fall as a consequence. PMID- 11777804 TI - Recent advances in minimal access surgery. PMID- 11777806 TI - Magnetic resonance imaging. PMID- 11777807 TI - Continuity of hospital care: beyond the question of personal contact. PMID- 11777808 TI - Informed consent: lessons from Australia. PMID- 11777809 TI - A case of murder and the BMJ. PMID- 11777811 TI - Steroid injections are helpful in rotator cuff tendinopathy. PMID- 11777812 TI - Teenage pregnancies are influenced by family structure. PMID- 11777813 TI - Inequalities and research need to be balanced. PMID- 11777814 TI - Phytoestrogens and menopause. Published evidence supports a role for phytoestrogens in menopause. PMID- 11777815 TI - Does lack of video mean GP registrar is not competent GP? PMID- 11777822 TI - Autoantibodies to extractable nuclear antigens: making detection and interpretation more meaningful. PMID- 11777823 TI - Natural history of Bartonella infections (an exception to Koch's postulate). PMID- 11777824 TI - Viral replication and host gene expression in alveolar macrophages infected with Ebola virus (Zaire strain). AB - In order to characterize the cellular response to and identify potential diagnostic markers for the early detection of Ebola virus, an in vitro culture system involving nonhuman primate alveolar macrophages was developed. Ebola virus replication in the alveolar macrophages was characterized by plaque assay, immunohistochemical analysis, and in situ hybridization. Fluorogenic 5'-nuclease assays specific for nonhuman primate proinflammatory cytokines and chemokines were designed and used to evaluate mRNA transcription in macrophages infected with Ebola virus. Transient increases in cytokine and chemokine mRNA levels were observed immediately following exposure to Ebola virus. At 2 h postexposure, levels of cytokine and chemokine mRNAs were markedly reduced. Although Ebola virus infection of alveolar macrophages failed to induce a sustained increase in proinflammatory cytokine and chemokine mRNA transcription (potentially reducing the use of these markers as diagnostic tools), the fluorogenic 5'-nuclease assays developed may have prognostic value for individuals infected with Ebola virus. Recently published data have indicated that persons who remain asymptomatic after exposure to Ebola virus are capable of mounting an early proinflammatory cytokine response and that those who become clinically ill are not. If implemented immediately after exposure, these assays could be used to predict which individuals will be more likely to remain asymptomatic as opposed to those who will be more likely to develop clinical signs and eventually succumb to the virus. PMID- 11777825 TI - Increased anionic peptide distribution and intensity during progression and resolution of bacterial pneumonia. AB - Anionic peptides (APs) are small anionic antimicrobial peptides composed of 7 aspartic acid residues and are produced in the lungs of humans, sheep, and cattle. Although expression by epithelial cells of some antimicrobial peptides (e.g., beta-defensins) of humans and ruminants is increased in response to acute infection, AP expression is not increased during acute infection, which suggests that the expression of the latter peptide is constitutive. In this study, the degree of AP expression during the progression (acute, subacute, and chronic) of bronchopneumonia was determined. Mannheimia (Pasteurella) haemolytica, a known inducer of bovinebeta-defensins, was inoculated intrabronchially with a fiber optic bronchoscope in nine 3-month-old sheep, and tissues were collected at 1, 15, and 45 days postinoculation (p.i.); nine control animals received pyrogen free saline by the same procedure and were killed at the same time points. In the acute group (1 day p.i.), the lungs had lesions typical of bronchopneumonia and the distribution and intensity of AP immunoreactivity (AP-IR) were similar to those of previous studies (minimal intensity and distribution of AP-IR in bronchiolar epithelial cells). In the subacute group (15 days p.i.), there was prominent hyperplasia of bronchiolar and alveolar epithelial cells, and the chronic group (45 days p.i.) had yet more pronounced hyperplasia. In the subacute and chronic groups, the intensity and distribution of AP-IR in the cytoplasm of hyperplastic bronchiolar and type II alveolar cells were significantly increased compared to those of saline-inoculated and contralateral (noninoculated) lung lobes. Although AP expression appears constitutive, the constitutive production of AP is higher in hyperplastic, less differentiated cells than in fully differentiated, mature cells of the respiratory airways. The increased intensity and distribution of AP-IR in immature (hyperplastic) epithelial cells may be a mechanism by which production of a noninducible antimicrobial is increased temporarily during lesion progression and repair. This increased production of AP by hyperplastic cells may protect the lung against further infection until new, fully differentiated epithelial cells are capable of expressing their own inducible array of antimicrobial peptides. PMID- 11777826 TI - Modified indirect porcine circovirus (PCV) type 2-based and recombinant capsid protein (ORF2)-based enzyme-linked immunosorbent assays for detection of antibodies to PCV. AB - Postweaning multisystemic wasting syndrome of swine associated with porcine circovirus (PCV) is a recently reported and economically important disease. Simple and reliable diagnostic methods are needed for detecting antibodies to PCV type 2 (PCV2) for monitoring of PCV infection. Here, we report the development of two modified indirect enzyme-linked immunosorbent assays (ELISAs): a PCV2 ELISA based on cell-culture-propagated PCV2 and an ORF2 ELISA based on recombinant major capsid protein. PCV2 and ORF2 ELISA detected antibodies to PCV2 and the capsid protein, respectively, in sera from pigs experimentally infected with PCV2 as early as 14 and 21 days postinoculation (dpi). The kinetics of the antibody response to PCV2 and the major capsid protein were similar. Repeatability tests revealed that the coefficients of variation of positive sera within and between runs for both assays were less than 30%. To validate the assays, PCV2 and ORF2 ELISAs were performed with 783 serum samples of young and adult pigs collected from different herds in the Midwestern United States and compared with an indirect immunofluorescent assay (IIF). Six out of 60 samples collected from nursery and growing pigs in 1987 were positive by both ELISA and IIF. Compared with IIF, the diagnostic sensitivity, specificity, and accuracy of PCV2 and ORF2 ELISAs were similar (>90%). The tests showed no cross-reactivity with antibodies to porcine parvovirus and porcine reproductive and respiratory syndrome virus. There was good agreement between the two ELISAs and between the ELISAs and IIF. The availability of the two ELISAs should accelerate our understanding of the host immune response to PCV2 and facilitate the development of prevention and control strategies by elucidating the ecology of PCV2 within swine populations. PMID- 11777827 TI - Development of internal controls for the Luminex instrument as part of a multiplex seven-analyte viral respiratory antibody profile. AB - The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument's ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument's multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay. PMID- 11777829 TI - Bacteroides ovatus as the predominant commensal intestinal microbe causing a systemic antibody response in inflammatory bowel disease. AB - To clarify what bacterial species of commensal intestinal microbes are recognized as the antigens that induce a serum antibody response in patients with inflammatory bowel disease (IBD), 72 subjects consisting of 12 Crohn's disease patients, 30 ulcerative colitis patients, and 30 healthy volunteers were examined for their titers of serum antibody to these intestinal bacteria. In IBD patients, as a result, significant elevations of both the immunoglobulin G (IgG) and IgA titers to Bacteroides ovatus were found. Immunoblotting showed that a definite 19.5-kDa band of B. ovatus was bound to the serum antibody raised in IBD patients. It was thus concluded that B. ovatus causes serum antibody responses in IBD patients, and a 19.5-kDa molecule of this bacterium appears to be the responsible antigen, although the role of this event in pathogenesis remains unclear. PMID- 11777828 TI - Immunological characterization of Escherichia coli O157:H7 intimin gamma1. AB - Portions of the intimin genes of Escherichia coli O157:H7 strain E319 and of the enteropathogenic E. coli O127:H6 strain E2348/69 were amplified by PCR and cloned into pET-28a+ expression vectors. The entire 934 amino acids (aa) of E. coli O157:H7 intimin, the C-terminal 306 aa of E. coli O157:H7 intimin, and the C terminal 311 aa of E. coli O127:H6 intimin were expressed as proteins fused with a six-histidine residue tag (six-His tag) in pET-28a+. Rabbit antisera raised against the six-His tag-full-length E. coli O157:H7 intimin protein fusion cross reacted in slot and Western blots with outer membrane protein preparations from the majority of enterohemorrhagic and enteropathogenic E. coli serotypes which have the intimin gene. The E. coli strains tested included isolates from humans and animals which produce intimin types alpha (O serogroups 86, 127, and 142), beta1 (O serogroups 5, 26, 46, 69, 111, 126, and 128), gamma 1 (O serogroups 55, 145, and 157), gamma 2 (O serogroups 111 and 103), and epsilon (O serogroup 103) and a nontypeable intimin (O serogroup 80), results based on intimin type specific PCR assays. Rabbit antisera raised against the E. coli O157:H7 C terminal fusion protein were much more intimin type-specific than those raised against the full-length intimin fusion protein, but some cross-reaction with other intimin types was also observed for these antisera. In contrast, the monoclonal antibody Intgamma1.C11, raised against the C-terminal E. coli O157 intimin, reacted only with preparations from intimin gamma 1-producing E. coli strains such as E. coli O157:H7. PMID- 11777830 TI - Identification of Acinetobacter isolates from species belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex with monoclonal antibodies specific for O Antigens of their lipopolysaccharides. AB - The unambiguous identification of Acinetobacter strains, particularly those belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex, is often hindered by their close geno- and phenotypic relationships. In this study, monoclonal antibodies (MAbs) against the O antigens of the lipopolysaccharides from strains belonging to the A. calcoaceticus-A. baumannii complex were generated after the immunization of mice with heat-killed bacteria and shown by enzyme immunoassays and Western blotting to be specific for their homologous antigens. Since the A. calcoaceticus-A. baumannii complex comprises the most clinically relevant species, the MAbs were subsequently tested in dot and Western blots with proteinase K-treated lysates from a large collection of Acinetobacter isolates (n = 631) to determine whether the antibodies could be used for the reliable identification of strains from this complex. Reactivity was observed with 273 of the 504 isolates (54%) from the A. calcoaceticus-A. baumannii complex which were included in this study. Isolates which reacted positively did so with only one antibody; no reactivity was observed with isolates not belonging to the A. calcoaceticus-A. baumannii complex (n = 127). To identify additional putative O serotypes, isolates from the A. calcoaceticus-A. baumannii complex which showed no MAb reactivity were subjected to a method that enables the detection of lipid A moieties in lipopolysaccharides with a specific MAb on Western blots following acidic treatment of the membrane. By this method, additional serotypes were indeed identified, thus indicating which strains to select for future immunizations. This study contributes to the completion of a serotype-based identification scheme for Acinetobacter species, in particular, those which are presently of the most clinical importance. PMID- 11777831 TI - Antibodies to 60-kilodalton heat shock protein and outer membrane protein 2 of Chlamydia pneumoniae in patients with coronary heart disease. AB - Evidence linking Chlamydia pneumoniae infection to atherosclerosis and to atherothrombotic events has recently emerged. A primary candidate implicated in these pathogenetic events is the 60-kDa chlamydial heat shock protein (HSP60). Another putative candidate to activate a potential proinflammatory mechanism is the chlamydial outer membrane protein 2 (OMP2). We have generated both HSP60 and OMP2 recombinant antigens in a nondenatured form and shown that (i) the two antigens were highly immunogenic in mice and (ii) murine antisera thus generated recognized the native C. pneumoniae proteins. We measured by enzyme linked immunosorbent assay (ELISA) and immunoblot assay antibody titers to the recombinant antigens in samples from 219 patients with coronary heart disease (CHD), 179 patients with unstable angina (UA), 40 patients with acute myocardial infarction (AMI), and 100 age-, sex-, and risk factor-matched healthy controls. We also examined whether anti-HSP60 and/or anti-OMP2 antibodies correlated with anti-C. pneumoniae antibodies assessed by a commercial microimmunofluorescence (MIF) assay. Immunoglobulin G (IgG), but neither IgA nor IgM, antibodies against the two recombinant proteins were detected by ELISA. In particular, anti-HSP60 antibodies were detected in >99% of CHD patients versus 0% of the controls, whereas the proportions of anti-OMP2 positive subjects were >70 and 27%, respectively. Nonetheless, among CHD patients, similar frequencies of positive subjects and titers of anti-HSP60 or anti-OMP2 antibodies were present in UA and AMI subjects. The anti-OMP2, but not the anti-HSP60, antibodies showed high specificity. Consistently, high serological correlation was observed between IgG MIF titers and IgG ELISA reactivity to OMP2 but not to HSP60. Overall, the results of this study demonstrate a strong correlation between CHD and anti-HSP60 IgG levels, as measured by our in-house ELISA. They also suggest that recombinant OMP2 ELISA, because of its high specificity and strong correlation with MIF assay, could be a candidate diagnostic marker for C. pneumoniae infection, which would be of potential usefulness for its specificity and nonsubjective nature. PMID- 11777832 TI - Production and application of new monoclonal antibodies specific for a fecal Helicobacter pylori antigen. AB - The aim of the present study was to establish monoclonal antibodies that could be used to produce a diagnostic test composed of one kind of monoclonal antibody recognizing a fecal Helicobacter pylori antigen. The need to develop such a test arose from disadvantages of the diagnostic test that uses a polyclonal antibody or plural kinds of monoclonal antibodies, such as the lower specificity for H. pylori antigen and the difficulty of reproduction with consistent quality. Mice were immunized with sonicated cells of the coccoid form of H. pylori, and fecal samples from H. pylori-positive subjects were screened by a direct sandwich enzyme immunoassay (EIA) for antibody production from 32 hybridoma clones. The three stable clones produced antibodies (21G2, 41A5, and 82B9) that reacted with the same soluble antigen. Gel filtration chromatography showed that the molecular masses of the cellular antigen and the fecal antigen were the same, 260 kDa. The antigen was labile in response to sodium dodecyl sulfate and heat treatments. A single-step direct sandwich EIA using a single monoclonal antibody, 21G2, was developed. The EIA could detect the antigen in 41 H. pylori clinical isolates and in fecal samples from seven H. pylori-positive subjects. Several kinds of Helicobacter species (Helicobacter felis, Helicobacter hepaticus, Helicobacter mustelae, and Helicobacter cinaedi) except H. pylori, major bacteria in feces (Campylobacter jejuni, Bacteroides vulgatus, Bifidobacterium breve, Bifidobacterium infantis, and Escherichia coli), and fecal samples from six H. pylori-negative subjects showed negative results. These results indicate that the new monoclonal antibodies and the new specific EIA would be useful as a noninvasive method of diagnosis of H. pylori infection. PMID- 11777833 TI - Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies. AB - In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease. PMID- 11777835 TI - Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but not L. rhamnosus GG in the human vagina as demonstrated by randomly amplified polymorphic DNA. AB - Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 are well-characterized probiotic strains with efficacy in the prevention and treatment of urogenital infections in women. The aim of the present study was to apply a molecular biology-based methodology for the detection of these strains and L. rhamnosus GG (a commercially available intestinal probiotic) in the human vagina in order to assess probiotic persistence at this site. Ten healthy women inserted vaginally a capsule containing either a combination of strains GR-1 and RC-14 or the GG strain for 3 consecutive nights. Vaginal swabs taken before and at various time points after probiotic insertion were analyzed, and the Lactobacillus flora was assessed by randomly amplified polymorphic DNA (RAPD) analysis. This method generated discrete DNA fingerprints for GR-1, RC-14, and GG and enabled successful detection of these strains in the vagina. Strain GR-1 and/or strain RC 14 was found to persist in the vaginal tract for up to 19 days after vaginal instillation, while L. rhamnosus GG was detectable for up to 5 days postadministration. In conclusion, the fates of probiotic L. rhamnosus and L. fermentum strains were successfully monitored in the human vagina by RAPD analysis. This technique provides molecular biology-based evidence that RC-14 and GR-1, strains selected as urogenital probiotics, persist in the human vagina and may be more suited to vaginal colonization than L. rhamnosus GG. This highlights the importance of proper selection of strains for urogenital probiotic applications. PMID- 11777834 TI - Lymphocyte depletion in ileal Peyer's patch follicles in lambs infected with Eimeria ovinoidalis. AB - A total of 14 lambs were experimentally infected with Eimeria ovinoidalis in two separate experiments in two consecutive years. Nine lambs served as uninoculated controls. Material was collected from the ileum 2 weeks after infection in eight lambs and 3 weeks after infection in six lambs. Lambs examined 2 weeks after infection had normal follicles. After three weeks, the follicle-associated epithelium covering the lymphoid follicles of the ileal Peyer's patches showed fusions with adjacent absorptive epithelium, focal hyperplasia, and occasionally necrosis. Macrogametes, microgamonts, and oocysts were often found in the follicle-associated epithelium and the dome region. Various degrees of lymphocyte depletion were present in the ileal lymphoid follicles in all six infected lambs 3 weeks after infection, and four lambs had decreased follicle size. Reduced staining for leukocyte common antigen (CD45), B-cell markers, and the proliferation marker Ki-67 was present in these lambs. Application of the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method for apoptotic cells revealed decreased staining in the ileal lymphoid follicles 3 weeks after infection. A marker of follicular dendritic cells, 5'- nucleotidase, showed increased reactivity, probably due to condensation of reticular cells following loss of follicle lymphocytes. Reduced staining for carbonic anhydrase in the follicle-associated epithelium and the domes was present in all six lambs examined 3 weeks after infection, indicating decreased production of carbonic anhydrase-reactive 50-nm particles and a decreased lymphoproliferative stimulus. In conclusion, the present study shows that severe E. ovinoidalis infection in lambs causes lesions of the follicle-associated epithelium and may result in lymphocyte depletion and atrophy of the ileal Peyer's patch follicles. PMID- 11777836 TI - Specific serum immunoglobulin G response to urease and CagA antigens of Helicobacter pylori in infected children and adults in a country with high prevalence of infection. AB - Few studies have analyzed the immune response to Helicobacter pylori CagA and urease antigens across age groups in the same population. The aim of this study was to analyze the serologic immunoglobulin G (IgG) response to CagA and urease proteins in children and adults with gastrointestinal symptoms and belonging to the same population and similar socioeconomic levels. The serologic response was studied in 352 children and 293 adults with gastrointestinal symptoms. IgG antibodies against CagA and urease were tested by enzyme-linked immunosorbent assay methods using highly purified recombinant antigens. H. pylori infection was defined as a positive result in a serologic assay using whole-cell H. pylori extracts as the antigen. We found, in H. pylori-positive children, a seroprevalence of 46.9% to CagA and 16.2% to urease, whereas in H. pylori positive adults, a seroprevalence of 78.9% to CagA and 59% to urease was found. In children, the magnitude of the response to CagA was significantly higher and the response to urease was significantly lower than those in adults. The kinetics of serologic response to CagA and to urease across age groups was contrastably different. Whereas CagA is a strong immunogen, urease is a poor immunogen during natural infection. These differences in the humoral response may be important for the short-term or long-term outcome of the infection. These results add to our knowledge of the epidemiology of H. pylori infection. PMID- 11777838 TI - Augmentation of cellular immunity and reduction of influenza virus titer in aged mice fed Lactobacillus casei strain Shirota. AB - We investigated whether oral administration of Lactobacillus casei strain Shirota activates the cellular immune system and ameliorates influenza virus (IFV) titer in the nasal site in upper respiratory IFV infection by using aged mice. Natural killer activity of splenocytes and lung cells of aged mice fed an L. casei strain Shirota diet (L.casei strain Shirota group) was significantly (P < 0.01 and P < 0.05) increased compared to those fed a control diet (control group). The increases were 1.5- and 2.5-fold, respectively. In aged mice fed an XL.casei strain Shirota diet, potent induction of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-gamma and TNF-alpha production increased 12- and 3.5-fold, respectively. In this model of upper respiratory IFV infection, the titer of IFV in the nasal washings of aged mice fed an L.casei strain Shirota diet was significantly (P < 0.05) lower than that in aged mice fed a control diet (10(1.6 +/- 0.6) and 10(2.2 +/- 0.5), respectively). These findings suggest that oral administration of L.casei strain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection. PMID- 11777837 TI - Immunoglobulin E antileishmanial antibody response in cutaneous leishmaniasis. AB - High levels of antileishmanial immunoglobulin E (IgE) antibodies are associated with disease activity in visceral leishmaniasis. Herein, we report our observations about the relationship between antileishmanial IgE antibodies and clinical aspects of cutaneous leishmaniasis. This study was carried out with 45 patients (29 male and 16 female), with ages ranging from 11 to 48 years. All subjects were from an area to which leishmaniasis is endemic, Corte de Pedra (Bahia, Brazil), and the duration of the illness was 6 h, P = 0.0001). These factors could impact diagnostic methods that rely on the immunoglobulin concentration in OF specimens. PMID- 11777856 TI - Dengue virus replicative intermediate RNA detection by reverse transcription-PCR. AB - Dengue virus replication involves synthesis of a replicative intermediate RNA (RI RNA), whose presence reveals an actual infection. We report on a simple and rapid reverse transcription-PCR for the detection of viral RI-RNA in infected cells. The product is demonstrated at 20 min postinfection. This method is useful for the study of virus-cell tropism. PMID- 11777857 TI - Biological activity of a mouse-human chimeric immunoglobulin G2 antibody to Cryptococcus neoformans polysaccharide. AB - The variable regions of the heavy and light chains of the protective murine monoclonal antibody (MAb) 2H1 (m2H1) were expressed with the human constant region genes for immunoglobulin G2 (IgG2) and kappa, respectively, to construct a chimeric antibody (ch2H1). ch2H1 retains the specificity of the parent MAb, exhibits biological activity, and lacks the toxicity of the parent murine IgG1 in chronically infected mice. PMID- 11777858 TI - Increased levels of lipopolysaccharide binding protein in plasma in children with kawasaki disease. PMID- 11777859 TI - Airway management in the emergency department. AB - Airway management in the emergency department and the role of anaesthetists and emergency physicians is reviewed. The training for emergency physicians in the advanced airway skills of rapid sequence induction and tracheal intubation is discussed. PMID- 11777861 TI - Emergency analgesia in the paediatric population. Part I: current practice and perspectives. AB - Children frequently present to the accident and emergency (A&E) department in pain. Most presentations are acute, but children with pain of longer duration also present. Children also often undergo painful procedures in A&E in the process of diagnosis or treatment. These papers review recent literature to examine factors involved in the provision of emergency analgesia in the paediatric population. This will include a discussion of current practice and make recommendations for future management of children's pain and anxiety in the A&E department. Part I: Current practice and perspectives. Part II: Pharmacological methods of paediatric analgesia. Part III: Non-pharmacological methods of pain control and anxiolysis. Part IV: Paediatric sedation in accident and emergency. PMID- 11777862 TI - Myocardial contusion: emergency investigation and diagnosis. AB - Cardiac contusion is an infrequent but occasionally serious complication of deceleration injury. According to ATLS teaching, the true diagnosis of contusion can only be established by direct inspection of the myocardium. The clinically important sequelae of myocardial contusion are hypotension and arrhythmia. Despite recent advances in investigative techniques, myocardial trauma remains an important diagnostic and management challenge. This paper presents an evidence based review of the topic. PMID- 11777863 TI - Apparent life threatening events in infants presenting to an emergency department. AB - OBJECTIVE: To describe the aetiology and outcome of apparent life threatening events (ALTE) presenting to an emergency department (ED), and to assess the value of an initial investigation protocol. DESIGN: A 12 month prospective study of infants under 1 year of age who presented to a children's hospital ED after an ALTE. A standardised history sheet and initial investigation protocol were used. All infants were admitted to hospital and followed up at six months. RESULTS: There were 65 infants recruited, median age 7 weeks. None had died at the time of writing. Diagnoses included gastro-oesophageal reflux n=17 (26%), pertussis, n=6 (9%), seizures, n=6 (9%), urinary tract infection (5), factitious illness (2), brain tumour, atrial tachycardia, persistent ductus arteriosus and opioid related apnoea. No diagnosis was reached in 15 cases (23%). Fifty seven (88%) had only one admission to hospital for ALTE. More serious diagnoses were associated with a presentation age over 2 months, abnormal initial clinical examination, and recurrent ALTE. CONCLUSIONS: ALTEs presenting to the ED may remain as a single, unexplained event or be attributable to numerous causes, ranging from minor to serious. Knowledge of the commoner causes and factors associated with higher risk could result in a more targeted approach, improving the decision making process and benefiting both infants and parents. PMID- 11777864 TI - Presentation to accident and emergency with crying or screaming and likelihood of child protection registration. AB - OBJECTIVES: To determine whether children aged less than 2 years who present to accident and emergency (A&E) with crying or screaming as the only complaint, are more likely to be placed on the child protection register in later years than children who do not attend with crying or screaming alone. METHODS: The Sheffield Children's Hospital A&E database was examined for five years from 1 January 1992. Children who presented at triage with crying or screaming as their sole complaint were identified. Controls were taken from children who presented with any other complaint. Matches were made for sex, postcode and date of birth. All names were checked against against files that contained dates of past or present child protection registration. In January 2000, the children's age ranged from 3 to 10 years. The mean follow up period was six years (SD one year seven months). RESULTS: From 1 January 1992 until 31 December 1996, 450 children made 462 attendances to A&E with crying or screaming as their only complaint. Of these, 12 had been placed on the child protection register. Ten of the 450 control children had been registered. The odds ratio of subsequent child protection registration if a child presents in Sheffield with crying or screaming alone is 1.21 (95% confidence intervals 0.52 to 2.82). CONCLUSIONS: Presentation of young children who cry or scream for no clear reason is relatively common. Although child protection registration is not the same as abuse, it is the closest surrogate marker we have. This study shows there is no evidence of increased likelihood of child protection registration for children who present with crying or screaming alone and prejudices against parents of these children, if held, are inappropriate. PMID- 11777865 TI - Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial. AB - OBJECTIVE: To compare the short-term effectiveness of ceftriaxone single dose followed by cefixime with a standard treatment of acute uncomplicated pyelonephritis in women. METHODS: An open, prospective, and randomised trial of women with acute uncomplicated pyelonephritis was performed. Group A were given a daily intravenous dose of 1 g ceftriaxone; group B: ceftriaxone 1 g intravenous single dose followed by oral cefixime. When urine culture was received, both groups completed a 10 day treatment based in sensitivity studies. Only women with positive initial urine culture were included. After three days of treatment, clinical and bacteriological efficacy was assessed. Clinical response was classified as "cured" if acute symptoms (fever, urinary syndrome and flank pain) were settled. Bacteriological response was classified as: eradication, or no eradication. RESULTS: Of 144 eligible patients, urine culture was positive in 54 of 72 (75%) women in group A and 51 of 72 (71%) in group B. There were no significant differences between groups in resolution of acute symptoms. Clinical cure was observed in 49 of 54 (91%) patients in the group A and in 47 of 51 (92%) patients in the group B (p = 0.68). After three days of treatment urine culture was negative for all patients. No adverse effects were observed in either of the groups. CONCLUSION: These data suggest that a intravenous single dose of ceftriaxone followed by oral cefixime is both effective and safe for the initial treatment of acute uncomplicated pyelonephritis in women. This regimen could be useful in managing selected patients with pyelonephritis as outpatients. PMID- 11777866 TI - Risk stratification of patients with syncope in an accident and emergency department. AB - OBJECTIVES: This study categorised syncopal patients, in a British accident and emergency (A&E) department, into three prognostic groups, using American College of Physicians (ACP) guidelines. The one year mortality of the three groups was studied to see if risk stratification using these guidelines is applicable to these patients and also whether admission improved outcome. METHODS: The records of all syncopal patients presenting to the Leeds General Infirmary A&E department during an eight week period from 2 November 1998 were identified. The cohort was grouped according to ACP guidelines into those who had an absolute indication for admission (group 1), a probable indication for admission (group 2) and no indication for admission (group 3). The actual disposal was recorded and for each patient mortality data were retrieved from general practices or health authorities one year later. The three groups were compared. RESULTS: Two hundred and ten records (1.7% of all new patients aged 16 years or above) were analysed. Forty per cent of the cohort were not assigned a diagnosis after their assessment in A&E. Forty seven (22%) were placed in ACP group 1, 63 (30%) in ACP group 2 and 100 (48%) in ACP group 3. Thirty six per cent of those in group 1 had died within a year, 14% of those in group 2 and none of those in group 3. In neither group 1 patients ("high risk") nor group 2 patients ("moderate risk") did admission to the hospital seem to influence outcome. However, three patients died within a week of their presentation, and two of them had been discharged from A&E. CONCLUSION: It is possible to stratify syncopal patients presenting acutely to A&E, according to prognosis, using ACP guidelines. Disposal decisions for these patients should be based on their apparent prognosis (as defined in the ACP guidelines) and not on the diagnosis, which is often difficult to make. PMID- 11777867 TI - The effect of a separate stream for minor injuries on accident and emergency department waiting times. AB - INTRODUCTION: To decrease waiting times within accident and emergency (A&E) departments, various initiatives have been suggested including the use of a separate stream of care for minor injuries ("fast track"). This study aimed to assess whether a separate stream of minor injuries care in a UK A&E department decreases the waiting time, without delaying the care of those with more serious injury. INTERVENTION: A doctor saw any ambulant patients with injuries not requiring an examination couch or an urgent intervention. Any patients requiring further treatment were returned to the sub-wait area until a nurse could see them in another cubicle. METHOD: Data were retrospectively extracted from the routine hospital information systems for all patients attending the A&E department for five weeks before the institution of the separate stream system and for five weeks after. RESULTS: 13 918 new patients were seen during the 10 week study period; 7117 (51.1%) in the first five week period and 6801 (49.9%) in the second five week period when a separate stream was operational. Recorded time to see a doctor ranged from 0-850 minutes. Comparison of the two five week periods demonstrated that the proportion of patients waiting less than 30 and less than 60 minutes both improved (p<0.0001). The relative risk of waiting more than one hour decreased by 32%. The improvements in waiting times were not at the expense of patients with more urgent needs. CONCLUSIONS: The introduction of a separate stream for minor injuries can produce an improvement in the number of trauma patients waiting over an hour of about 30%. If this is associated with an increase in consultant presence on the shop floor it may be possible to achieve a 50% improvement. It is recommended that departments use a separate stream for minor injuries to decrease the number of patients enduring long waits in A&E departments. PMID- 11777868 TI - TOXBASE: poisons information on the internet. AB - OBJECTIVES: To assess the uptake, usage and acceptability of TOXBASE, the National Poisons Information Service internet toxicology information service. METHODS: An observational study of database usage, and a questionnaire of users were undertaken involving users of TOXBASE within the UK between August 1999, when the internet site was launched, and May 2000. The main outcome measures were numbers of registered users, usage patterns on the database, responses to user satisfaction questionnaire. RESULTS: The number of registered users increased from 567 to 1500. There was a 68% increase in accident and emergency departments registered, a 159% increase in general practitioners, but a 324% increase in other hospital departments. Between January 2000 and the end of May there had been 60 281 accesses to the product database, the most frequent to the paracetamol entry (7291 accesses). Ecstasy was the seventh most frequent entry accessed. Altogether 165 of 330 questionnaires were returned. The majority came from accident and emergency departments, the major users of the system. Users were generally well (>95%) satisfied with ease and speed of access. A number of suggestions for improvements were put forward. CONCLUSIONS: TOXBASE has been extensively accessed since being placed on the internet (http://www.spib.axl.co.uk). The pattern of enquiries mirrors clinical presentation with poisoning. The system seems to be easily used. It is a model for future delivery of treatment guidelines at the point of patient care. PMID- 11777869 TI - Detecting and reducing adverse events in an Australian rural base hospital emergency department using medical record screening and review. AB - OBJECTIVE: To determine if retrospective medical record screening and clinical review followed by appropriate action can effectively and efficiently detect and reduce adverse events in an emergency department. METHOD AND PARTICIPANTS: The medical records of 20 050 patients who attended the emergency department over a two year period were screened for adverse events using five general patient outcome criteria. Records that screened positive were reviewed by the hospital's clinical risk manager. If an adverse event was detected, the record was also reviewed by the director of emergency. For the first three months details of adverse events were recorded to determine a baseline adverse event rate, but no further action was taken. When an adverse event was found in the remaining 21 months, further analysis and recommendations for action to prevent a recurrence were made to relevant hospital staff. SETTING: A rural base hospital in the Wimmera region of Victoria, Australia between October 1997 and September 1999. RESULTS: Of all the patient attendances 573 (2.85%) were screened positive for one or more criteria. An adverse event was confirmed in 250 patient attendances (1.24% of all attendances). Of the adverse occurrences, 81 (32.4%) were determined to be of major severity and 169 (67.6%) of minor severity. Quality improvement activities, mostly changes to hospital policies and work processes, were implemented with the aim of preventing the recurrence of specific adverse patient events. Over two years the number of adverse events fell from 84 (3.26% of all patient attendances) in the pre-intervention quarter to 12 (0.48% of all patient attendances) in the final quarter (relative risk reduction 85.3% (95% CI, 62.7% to 100%)). CONCLUSIONS: Adverse events in emergency departments can be efficiently detected and their rate reduced using retrospective medical record screening together with clinical review, analysis and action to prevent recurrences. PMID- 11777870 TI - Injuries initially misdiagnosed as sprained wrist (beware the sprained wrist). AB - OBJECTIVES: To describe the injuries misdiagnosed as a sprain of the wrist and to determine the approximate incidence of misdiagnosis in patients diagnosed as having a sprain of the wrist. METHODS: All diagnostic errors in an accident and emergency (A&E) department were noted on a computerised database. Injuries initially misdiagnosed as wrist sprain are described and compared with the number of diagnoses of sprained wrist on the A&E department computer. RESULTS: 57 injuries initially diagnosed as a sprained wrist had a different diagnosis (1.76% of all diagnoses of sprained wrists). This is an underestimate of the true incidence of diagnostic error. Forty two per cent of the misdiagnoses were of greenstick or torus fractures of the distal radius. CONCLUSIONS: Training for junior doctors in A&E departments should be improved-especially training in radiological interpretation. Other methods of preventing diagnostic errors by misreading of radiographs, for example, more hot reporting of radiographs by radiologists or radiographers should be considered. PMID- 11777871 TI - Comparative prospective study of foreign body removal from external auditory canals of cadavers with right angle hook or cyanoacrylate glue. AB - OBJECTIVES: Foreign bodies of the external auditory canal are a relatively common problem in emergency departments. Repeated attempts at removal with standard instrumentation can lead to significant ear injury. Recent case reports of using cyanoacrylate impregnated cotton buds suggest this is less traumatic and well tolerated by patients. No studies on this method have been performed. The objectives of this study were to identify whether there were significant differences in success rate, duration and injury caused by extracting beads from the external auditory canals of adult cadaveric ears using two different methods. This is the first study in a planned series of anatomical and clinical studies relating to foreign body extraction from the external auditory canal. METHODS: In this study the success rate, time taken and injury rate were assessed for removal of impacted spherical foreign bodies in the external auditory canals of cadavers using both a blunt right angle hook and cotton buds impregnated with cyanoacrylate glue. This process was performed by a specialist registrar in otolaryngology and repeated by a specialist registrar in emergency medicine. RESULTS: It was shown that both methods had a statistically similar success rate (two tailed binomial test p=0.5) and no injury was identified for either method. In addition the median extraction time for a right angle hook was 6 seconds and 42 seconds for cyanoacrylate. It was also noted that failed extraction was associated with a poor view of the foreign body in the external canal. This was caused by hair, a large tragus or tortuous external canal. CONCLUSIONS: The authors feel that cyanoacrylate impregnated cotton buds are as effective at removing impacted foreign bodies as a right angle hook but the process takes longer. It is believed that patients could tolerate this longer time as the cyanoacrylate method is in theory less traumatic. PMID- 11777872 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Detection of pneumoperitoneum on erect chest radiograph. AB - A short cut review was carried out to establish whether a normal erect chest radiograph excludes the diagnosis of perforated abdominal viscus. Altogether 37 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are shown in table 1. A clinical bottom line is stated. PMID- 11777874 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Cervical spine radiography in alert asymptomatic blunt trauma patients. AB - A short cut review was carried out to establish whether a normal cervical spine radiograph excludes bony cervical spine injury in alert, asymptomatic trauma patients. Altogether 232 papers were found using the reported search, of which six presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are shown in table 2. A clinical bottom line is stated. PMID- 11777875 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. The use of antibiotics in venomous snake bite. AB - A short cut review was carried out to establish whether antibiotics reduce the incidence of infection after venomous snake bite. Altogether 60 papers were found using the reported search, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are shown in table 3. A clinical bottom line is stated. PMID- 11777876 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Antibiotics after puncture wounds to the foot. AB - A short cut review was carried out to establish whether antibiotics reduce infective complications after puncture wounds to the foot. A total of 29 papers were found using the reported search, of which none answered the question posed. Further research is needed in this area. PMID- 11777877 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Activated charcoal and gastric absorption of iron compounds. AB - A short cut review was carried out to establish whether activated charcoal is effective in iron overdose. Altogether 17 papers were found using the reported search, of which only one was relevant. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are shown in table 4. A clinical bottom line is stated. PMID- 11777878 TI - Aspiration of acute traumatic knee haemarthrosis. AB - A short cut review was carried out to establish whether aspiration of a traumatic knee haemarthrosis improved the patient's symptoms. Altogether 267 papers were found using the reported search, of which none answered the question posed. Further research is needed in this area. PMID- 11777880 TI - Simulated interactive management series. Article 6. Sex, drugs, and rock and roll. PMID- 11777879 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Phenytoin or paraldehyde as the second drug for convulsions in children. AB - A short cut review was carried out to establish whether phenytoin or paraldehyde should be given as the second drug for resistant fits in children. Altogether 41 papers were found using the reported search, of which none answered the question posed. Further research is needed in this area. PMID- 11777881 TI - A randomised trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation. AB - BACKGROUND: Ventricular fibrillation (VF) remains the most salvageable rhythm in patients suffering a cardiopulmonary arrest (CA). However, outcome remains poor if there is no response to initial defibrillation. Some evidence suggests that intravenous magnesium may prove to be an effective antiarrhythmic agent in such circumstances. STUDY HYPOTHESIS: Intravenous magnesium sulphate given early in the resuscitation phase for patients in refractory VF (VF after 3 DC shocks) or recurring VF will significantly improve their outcome, defined as a return of spontaneous circulation (ROSC) and discharge from hospital alive. DESIGN: A randomised, double blind, placebo controlled trial. Pre-defined primary and secondary endpoints were ROSC at the scene or in accident and emergency (A&E) and discharge from hospital alive respectively. SETTING, PARTICIPANTS, AND INTERVENTION: Patients in CA with refractory or recurrent VF treated in the prehospital phase by the county emergency medical services and/or in the A&E department. One hundred and five patients with refractory VF were recruited over a 15 month period and randomised to receive either 2-4 g of magnesium sulphate or placebo intravenously. RESULTS: Fifty two patients received magnesium treatment and 53 received placebo. The two groups were matched for most parameters including sex, response time for arrival at scene and airway interventions. There were no significant differences between magnesium and placebo for ROSC at the scene or A&E (17% v 13%). The 4% difference had 95% confidence intervals (CI) ranging from -10% to +18%. For patients being alive to discharge from hospital (4% v 2%) the difference was 2% (95% CI -7% to +11%). After adjustment for potential confounding variables (age, witnessed arrest, bystander cardiopulmonary resuscitation and system response time), the odds ratio (95% CI) for ROSC in patients treated with magnesium as compared with placebo was 1.69 (0.54 to 5.30). CONCLUSION: Intravenous magnesium given early in patients suffering CA with refractory or recurrent VF did not significantly improve the proportion with a ROSC or who were discharged from hospital alive. PMID- 11777882 TI - The potential role of prehospital administration of activated charcoal. AB - OBJECTIVES: Activated charcoal is now the mainstay of non-specific treatment for self poisoning in accident and emergency (A&E) departments and should be administered within one hour of ingestion of an overdose. This study aimed to investigate if compliance with treatment guidelines may be improved by the prehospital administration of activated charcoal. METHOD: Ambulance report forms and case notes were reviewed in all patients presenting to A&E by ambulance after self poisoning. Information was gathered using a standardised abstraction form. The times collected were: time of ingestion, time of call to ambulance control, time picked up, time of arrival in A&E and time seen by doctor. RESULTS: 201 patient records were reviewed. Twenty six were excluded because of incomplete data on report forms or case notes. The median time between ingestion and pick up by an ambulance crew was 77 minutes. This compares with a median of 140 minutes for the time to assessment by medical staff. Seventy three patients were picked up by an ambulance within one hour of overdose, only 11 (15%) of these were seen by medical staff within an hour of ingestion. Forty nine of these 73 patients would have been suitable candidates to receive activated charcoal. CONCLUSIONS: The prehospital administration of charcoal provides an opportunity to comply with international guidelines on reducing the absorption of a potentially fatal overdose. The administration of charcoal results in few side effects provided the patient can adequately protect their airway and ambulance staff could be trained in its use. Further studies would be necessary to investigate if this would effect clinical outcome. PMID- 11777883 TI - Recognition of ST elevation by paramedics. AB - OBJECTIVE: To define the ability of UK paramedics to recognise ST segment elevation using a prehospital 12 lead electrocardiogram (ECG). METHODS: Analysis of the diagnostic ability of seven paramedics 12 months after a two day training course, using interpretation of a 12 lead ECG by two cardiologists as the criterion standard. Comparison of paramedic and A&E SHO diagnosis to determine accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of paramedic interpretation. RESULTS: Paramedics showed a median accuracy of 0.95 (95% CI 0.88 to 0.98), a specificity of 0.91 (95% CI 0.53 to 1.0), a sensitivity of 0.97 (95% CI 0.94 to 0.99), a NPV of 0.77 (95% CI 0.62 to 0.92) and a PPV of 0.99 (95% CI 0.92 to 1.0). This was not significantly different from a group of experienced A&E SHOs. CONCLUSIONS: UK paramedics can recognise ST elevation using a 12 lead ECG. Radio transmission of an ECG may not be necessary to pre-alert the hospital. PMID- 11777884 TI - Can nurses working in remote units accurately request and interpret radiographs? AB - OBJECTIVE: Recent changes in the NHS have seen nurses take on roles that are traditionally filled by doctors, leading to the development of emergency nurse practitioners (ENPs). In addition to this, increasing interest has focused on telemedicine (literally, medicine at a distance) as a way of supporting remote emergency departments and minor injuries units from larger centres. The vast majority of these consultations are related to peripheral limb trauma and require a radiograph to be viewed as an integral part of the telemedical consultation. The aim of this study was therefore to determine whether nurses working alone in a peripheral unit are able to appropriately request, and accurately interpret, peripheral limb radiographs. METHODS: In this prospective study the four qualified nurses working in a peripheral unit were permitted to request a defined set of radiographs after limb trauma. A written protocol for nurse requested radiographs was supported by individual teaching sessions. At the time that the radiograph was requested basic demographic details were recorded and the patient was also assessed by two senior doctors in emergency medicine, one in person and one via a telemedicine link, both of whom independently considered whether the radiograph requested by the nurse was appropriate in that patient. Nursing staff were also asked to provide a provisional interpretation of each film, and this was compared with a gold standard derived from the interpretations of the two emergency physicians who had seen the patient and the final radiologist's report. RESULTS: The first 300 patients who had a radiograph requested by a member of the nursing staff were studied over a period of 12 months. Altogether 93 radiographs (31%) were positive for recent bony trauma or radio-opaque foreign body. Eleven radiographs (3.7%) were judged by both emergency physicians to be inappropriate. Three radiographs (1%) were requested outside the limits of the protocol, but all three were judged to be appropriate and occurred within the first two months of the study. A total of 32 (10.7%) of the radiographs were incorrectly interpreted by nursing staff with 26 false positives, four false negatives and two cases where the nurse observed an abnormality but failed to identify it correctly. The sensitivity of nurse interpretation was therefore 96%, with a specificity of 87%. CONCLUSION: Experienced nurses, working without continuous medical supervision in a remote unit, are able to request appropriate radiographs of the peripheral limbs. Nurses requesting radiographs in this way can also interpret these films to a high standard, though with a tendency to err on the side of caution, generating many more false positive results than false negatives. PMID- 11777885 TI - Children and mini-magnets: an almost fatal attraction. AB - Children imitating adults often appear to indulge in harmless fun, however at times these activities have more serious implications. The recent fashion of body piercing among adults has encouraged children to have similar procedures or imitate them by applying small magnets to sustain the jewellery used in piercing in position. This paper describes a series of 24 cases presented to the Sheffield Children's Hospital over a period of eight weeks. The children imitated body piercing by using small powerful magnets across parts of their body including nose, ears, penis, and tongue. Some swallowed the magnets while attempting to use them, resulting in one near fatal surgical complication. The paper describes the details of the patients, the procedures used to detect the magnets, and the management of the different complications encountered. PMID- 11777886 TI - Recognising signs of danger: ECG changes resulting from an abnormal serum potassium concentration. AB - A number of metabolic insults can result in changes to the serum potassium concentration. Potassium is predominantly an intracellular cation, and it has an important role in determining the resting membrane potential of cells. Disruption of the potassium gradient across the cell membrane can result in impaired cellular functioning. This may affect a number of organs including the cardiovascular and central nervous systems, resulting in various neurological symptoms and cardiac arrhythmias. Though laboratory tests are the gold standard test for diagnosing changes in the serum electrolyte concentration, there may be delays in obtaining the results. The electrocardiogram (ECG) may be a useful diagnostic tool, if the clinician is aware of the possible changes resulting from abnormalities in the serum potassium concentration. This article presents three cases that highlight the ECG changes resulting from an abnormal serum potassium concentration and will briefly look at the treatment options to reduce the risk of life threatening arrhythmias occurring. PMID- 11777887 TI - Thyrotoxic periodic paralysis: reports of seven patients presenting with weakness in an Asian emergency department. AB - OBJECTIVES: This study was done to describe the features of thyrotoxic periodic paralysis in young Asian men. METHODS: Seven male patients were enlisted who presented to the emergency department over a period of three years with weakness and paralysis in the morning. RESULTS: Initial electrolyte studies revealed hypokalaemia in these patients, and later thyroid function tests confirmed thyrotoxicosis for all. Only two of these patients had clinical symptoms and signs of thyrotoxicosis, the others being asymptomatic. CONCLUSIONS: Early morning paralysis can be the first manifestation of hyperthyroidism in Asian men, without the other more typical symptoms of weight loss, increased appetite, excitability, sweaty palms or goitre. Treatment to a euthyroid state will ameliorate the syndrome. PMID- 11777888 TI - Hand injuries in young children from contact with vacuum cleaners. AB - OBJECTIVES: To assess the incidence of injuries to young children sustained by contact with a domestic vacuum cleaner and to highlight the potential for significant injury. An increase in public awareness of these risks might result in a reduction in morbidity. METHODS: Over a period of one year, all children attending with an injury sustained because of contact with a domestic vacuum cleaner had review of their case notes by the author. RESULTS: Four children were identified as having sustained friction burns to a hand after contact with a vacuum cleaner. All required treatment and several review appointments before satisfactory resolution was achieved. CONCLUSIONS: Although the number of cases seen was small, the potential for significant injury must be emphasised and public awareness increased in an attempt to reduce morbidity. PMID- 11777890 TI - Mercury: is it elemental my dear Watson? AB - A case of poisoning with a mercury "solution" is reported. The solution was known to contain mercury but its exact nature was unknown. Despite appropriate initial management, various assumptions were made that resulted in a "toxic" level. The presentation and management is discussed. PMID- 11777891 TI - Retroperitoneal haematoma after paracetamol increased anticoagulation. AB - Drugs containing paracetamol are widely used as analgesics but may result in increased anticoagulation in patients who take warfarin, the mechanism being unclear. Retroperitoneal haemorrhage is a serious and well described complication in patients who develop increased anticoagulation; this may result in a femoral neuropathy. Both conservative and surgical treatments have been advocated for this complication. PMID- 11777892 TI - Failure to recognise ventricular standstill. PMID- 11777893 TI - Rare presentation of a type I Monteggia fracture. AB - A rare case is reported of a Monteggia equivalent injury where a dislocation of the radial head is associated with fracture of the distal third of the radius and ulna. The mechanism, treatment and outcome are described. PMID- 11777894 TI - Bilateral spontaneous pneumothorax. PMID- 11777895 TI - Effectiveness of double Tubigrip in grade 1 and 2 ankle sprains. PMID- 11777896 TI - Intentional overdose of warfarin in an adolescent: need for follow up. PMID- 11777897 TI - Effectiveness of double Tubigrip in grade 1 and 2 ankle sprains. PMID- 11777898 TI - Calcium salts in management of hyperkalaemia. PMID- 11777899 TI - Volar metacarpophalangeal joint dislocation. PMID- 11777900 TI - Multiple cis elements within the Igf2/H19 insulator domain organize a distance dependent silencer. A cautionary note. AB - The 5'-flank of the H19 gene harbors a differentially methylated imprinting control region that represses the maternally derived Igf2 and paternally derived H19 alleles. Here we show that the H19 imprinting control region (ICR) is a potent silencer when positioned in a promoter-proximal position. The silencing effect is not alleviated by trichostatin A treatment, suggesting that it does not involve histone deacetylase functions. When the H19 ICR is separated from the promoter by more than 1.2 +/- 0.3 kb, however, trichostatin A stimulates promoter activity 10-fold. Deletion analyses revealed that the silencing feature extended throughout the ICR segment. Finally, chromatin immunopurification analyses revealed that the H19 ICR prevented trichostatin A-dependent reacetylation of histones in the promoter region in a proximal but not in a distal position. We argue that these features are likely to be side effects of the H19 ICR, rather than explaining the mechanism of silencing of the paternal H19 allele. We issue a cautionary note, therefore, that the interpretation of insulator/silencer data could be erroneous should the distance issue not be taken into consideration. PMID- 11777902 TI - beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. AB - beta-Arrestins are cytosolic proteins that mediate homologous desensitization of G protein-coupled receptors (GPCRs) by binding to agonist-occupied receptors and by uncoupling them from heterotrimeric G proteins. The recent finding that beta arrestins bind to some mitogen-activated protein (MAP) kinases has suggested that they might also function as scaffolds for GPCR-stimulated MAP kinase activation. To define the role of beta-arrestins in the regulation of ERK MAP kinases, we examined the effect of beta-arrestin overexpression on ERK1/2 activation and nuclear signaling in COS-7 cells expressing angiotensin II type 1a receptors (AT1aRs). Expression of either beta-arrestin1 or beta-arrestin2 reduced angiotensin-stimulated phosphatidylinositol hydrolysis but paradoxically increased angiotensin-stimulated ERK1/2 phosphorylation. The increase in ERK1/2 phosphorylation in beta-arrestin-expressing cells correlated with activation of a beta-arrestin-bound pool of ERK2. The beta-arrestin-dependent increase in ERK1/2 phosphorylation was accompanied by a significant reduction in ERK1/2-mediated, Elk1-driven transcription of a luciferase reporter. Analysis of the cellular distribution of phospho-ERK1/2 by confocal immunofluorescence microscopy and cellular fractionation revealed that overexpression of beta-arrestin resulted in a significant increase in the cytosolic pool of phospho-ERK1/2 and a corresponding decrease in the nuclear pool of phospho-ERK1/2 following angiotensin stimulation. beta-Arrestin overexpression resulted in formation of a cytoplasmic pool of beta-arrestin-bound phospho-ERK, decreased nuclear translocation of phospho-ERK1/2, and inhibition of Elk1-driven luciferase transcription even when ERK1/2 was activated by overexpression of cRaf-1 in the absence of AT1aR stimulation. These data demonstrate that beta-arrestins facilitate GPCR-mediated ERK activation but inhibit ERK-dependent transcription by binding to phospho-ERK1/2, leading to its retention in the cytosol. PMID- 11777901 TI - Transcription suppression of thromboxane receptor gene by peroxisome proliferator activated receptor-gamma via an interaction with Sp1 in vascular smooth muscle cells. AB - Thromboxane (TX) A(2) exerts contraction and proliferation of vascular smooth muscle cells (VSMCs) via its specific membrane TX receptor (TXR), possibly leading to the progression of atherosclerosis. A nuclear hormone receptor, peroxisome proliferator-activated receptor (PPAR)-gamma, has recently been reported to be expressed in VSMCs. Here we examined a role of PPAR-gamma in TXR gene expression in VSMCs. PPAR-gamma ligands 15-deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone reduced TXR mRNA expression levels as well as cell growth as assessed by [(3)H]thymidine incorporation. Transcriptional activity of the TXR gene promoter was suppressed with PPAR-gamma ligands, and the suppression was augmented further by PPAR-gamma overexpression. By deletion and mutation analyses, the transcription suppression was shown to be the result of a -22/-7 GC box-related sequence (upstream of transcription start site). Electrophoretic mobility shift assays also showed that the sequence was bound by Sp1 but not by PPAR-gamma, and the formation of a Sp1 small middle dotDNA complex was inhibited either by coincubation with PPAR-gamma or PPAR-gamma ligand treatment of VSMCs. Moreover, glutathione S-transferase pull-down assays demonstrated a direct interaction between PPAR-gamma and Sp1. In conclusion, PPAR-gamma suppresses TXR gene transcription via an interaction with Sp1. PPAR-gamma may possibly have an antiatherosclerotic action by inhibiting TXR gene expression in VSMCs. PMID- 11777903 TI - 17beta -Estradiol modulates mechanical strain-induced MAPK activation in mesangial cells. AB - Gender is an important determinant of clinical outcome across a broad spectrum of kidney diseases, but the mechanism(s) responsible for the protective effect of female gender have not been fully elucidated. Remnant kidney glomerular injury is limited in female rats compared with male rats despite similar elevations in glomerular capillary pressure. In vitro, mechanical strain leads to the activation of p44/42 mitogen-activated kinase (p44/42 MAPK) and Jun N-terminal kinase/stress-activated protein kinase (SAPK) in glomerular mesangial cells (MC). Accordingly, we studied the effect of 17beta-estradiol on mechanical strain induced signal transduction in MC. Exposure of MC to mechanical strain increased p44/42 MAPK activation (3-fold) and SAPK activation (2.5-fold), and kinase activation was inhibited by pretreatment with 17beta-estradiol (10(minus sign8) to 10(minus sign11) m) for 24 h in a dose-dependent manner. Mechanical strain induced nuclear translocation of p44/42 MAPK and SAPK and nuclear protein binding to AP-1 were also attenuated by 17beta-estradiol. The inhibitory effects of 17beta-estradiol were not reproduced by the cell-impermeable estrogen, BSA/17beta estradiol, nor did preincubation with 17beta-estradiol lead to actin cytoskeleton disassembly or impaired stress fiber formation. However, 17beta-estradiol did increase base-line levels of the dual specificity phosphatase MKP-1. The inhibitory effects of 17beta-estradiol on p44/42 MAPK activation and SAPK activation, translocation, and AP-1 binding were all abrogated by the estrogen receptor antagonist, ICI-182,780. We conclude that attenuation of mechanical strain-induced MAPK activation by 17beta-estradiol is dependent on intracellular estrogen receptor. The attenuation of stretch-induced kinase activation may be due, at least in part, to an effect of 17beta-estradiol on MKP-1 expression. Together, these findings add insight into the protective effect of gender on renal disease progression. PMID- 11777904 TI - Histidinyl radical formation in the self-peroxidation reaction of bovine copper zinc superoxide dismutase. AB - In the absence of suitable oxidizable substrates, the peroxidase reaction of copper-zinc superoxide dismutase (SOD) oxidizes SOD itself, ultimately resulting in its inactivation. A SOD-centered free radical adduct of 2-methyl-2 nitrosopropane (MNP) was detected upon incubation of SOD with the spin trap and a hydroperoxide (either H(2)O(2) or peracetic acid). Proteolysis by Pronase converted the anisotropic electron paramagnetic resonance (EPR) spectrum of MNP/(center dot)SOD to a nearly isotropic spectrum with resolved hyperfine couplings to several atoms with non-zero nuclear spin. Authentic histidinyl radical (from histidine + HO(center dot)) formed a MNP adduct with a very similar EPR spectrum to that of the Pronase-treated MNP/(center dot)SOD, suggesting that the latter was centered on a histidine residue. An additional hyperfine coupling was detected when histidine specifically (13)C-labeled at C-2 of the imidazole ring was used, providing evidence for trapping at that atom. All of the experimental spectra were convincingly simulated assuming hyperfine couplings to 2 nearly equivalent nitrogen atoms and 2 different protons, also consistent with trapping at C-2 of the imidazole ring. Free histidinyl radical consumed oxygen, implying peroxyl radical formation. MNP-inhibitable oxygen consumption was also observed when cuprous SOD but not cupric SOD was added to a H(2)O(2) solution. Formation of 2-oxohistidine, the stable product of the SOD-hydroperoxide reaction, required oxygen and was inhibited by MNP. These results support formation of a transient SOD-peroxyl radical. PMID- 11777905 TI - Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70. AB - Antibodies to histone deacetylases (HDACs) have been used to immuno-isolate deacetylase complexes from HeLa cell extracts. Complexes shown to contain HDAC1, HDAC3, HDAC6, and HDAC1+2 as their catalytic subunits have been used in an antibody-based assay that detects deacetylation of whole histones at defined lysines. The class II deacetylase HDAC6 was inactive in this assay, but the three class I enzymes deacetylated all histone lysines tested, although with varying efficiency. In comparison to HDAC1, HDAC3 preferentially deacetylated lysines 5 and 12 of H4 and lysine 5 of H2A. H4 tails in purified mononucleosomes were refractory to deacetylation by both HDAC1 and HDAC3, unless ATP was added to the reaction mix. Surprisingly, ATP also consistently enhanced cleavage of free, non nucleosomal histones, but not small peptides, by both enzyme complexes. We found no evidence that ATP operates by phosphorylation of components of the HDAC complex, but have shown that HDACs 1, 2, and 3 all co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70. Another common ATP-dependent chaperone, Hsp90, was absent from all HDAC complexes tested, whereas Hsp60 associated with HDAC1 only. We suggest that Hsp chaperone proteins enhance the deacetylase activity of HDAC complexes by ATP-dependent manipulation of protein substrates. PMID- 11777906 TI - Differential nucleocytoplasmic trafficking between the related endocytic proteins Eps15 and Eps15R. AB - Eps15 and Eps15R are constitutive components of clathrin-coated pits that are required for clathrin-dependent endocytosis. The most striking difference between these two related proteins is that Eps15R is also found in the nucleus, whereas Eps15 is excluded from this compartment at steady state. To better understand the individual functions of these two proteins, the mechanisms responsible for their different localization were investigated. Interestingly, some mutants of Eps15 were found in the nucleus. This nuclear localization was correlated with the loss of the last approximately 100 amino acids of Eps15, suggesting the presence of a nuclear export signal (NES) within this region. As expected, the last 25 amino acids contain a leucine-rich sequence matching with classical NESs, show a leptomycin B-sensitive nuclear export activity, and bind to the exportin CRM1 in a leucine residue-dependent manner. In contrast, no NES could be found in Eps15R, a result in keeping with its constitutive nuclear localization that appears to be regulated by alternative splicing. Altogether, these results are the first characterization of nucleocytoplasmic shuttling signals for endocytic proteins. They also provide an explanation for the different nuclear localization of Eps15 and Eps15R and further evidence for a possible nuclear function for Eps15 protein family members. PMID- 11777907 TI - beta-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a beta-arrestin binging site in beta 2-adaptin. AB - beta-Arrestins, proteins involved in the turn-off of G protein-coupled receptor (GPCR) activation, bind to the beta(2)-adaptin subunit of the clathrin adaptor AP 2. The interaction of beta(2)-adaptin with beta-arrestin involves critical arginine residues in the C-terminal domain of beta-arrestin and plays an important role in initiating clathrin-mediated endocytosis of the beta(2) adrenergic receptor (beta(2)AR) (Laporte, S. A., Oakley, R. H., Holt, J. A., Barak, L. S., and Caron, M. G. (2000) J. Biol. Chem. 275, 23120--23126). However, the beta-arrestin-binding site in beta(2)-adaptin has not been identified, and little is known about the role of beta-arrestin/AP-2 interaction in the endocytosis of other GPCRs. Using in vitro binding assays, we have identified two glutamate residues (Glu-849 and Glu-902) in beta(2)-adaptin that are important in beta-arrestin binding. These residues are located in the platform subdomain of the C terminus of beta(2)-adaptin, where accessory/adapter endocytic proteins for other classes of receptors interact, distinct from the main site where clathrin interacts. The functional significance of the beta-arrestin/AP-2/clathrin complex in the endocytosis of GPCRs such as the beta(2)AR and vasopressin type II receptor was evaluated using mutant constructs of the beta(2)-adaptin C terminus containing either the clathrin and the beta-arrestin binding domains or the beta arrestin-binding domain alone. When expressed in human embryonic kidney 293 cells, both constructs acted as dominant negatives inhibiting the agonist-induced internalization of the beta(2)AR and the vasopressin type II receptor. In addition, although the beta(2)-adaptin construct containing both the clathrin and beta-arrestin binding domains was able to block the endocytosis of transferrin receptors, a beta(2)-adaptin construct capable of associating with beta-arrestin but lacking its high affinity clathrin interaction did not interfere with transferrin receptor endocytosis. These results suggest that the interaction of beta-arrestin with beta(2)-adaptin represents a selective endocytic trigger for several members of the GPCR family. PMID- 11777908 TI - Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells. AB - We previously found that bikunin (bik), a Kunitz-type protease inhibitor, suppresses phorbol ester (PMA)-stimulated expression of urokinase-type plasminogen activator (uPA). In the present study, we tried to answer this mechanism using human chondrosarcoma HCS-2/8 cells. Our results showed the following novel findings: (a) the standard form of CD44 (CD44s; 85 kDa) is expressed in both unstimulated and PMA-stimulated cells, while CD44v isoforms containing epitope v9 (110 kDa) are strongly up-regulated in response to treatment with PMA; (b) CD44v isoforms containing epitope v9 present on the same cell exclusively form aggregates in stimulated cells; (c) induction of uPA mRNA expression could be achieved by using a second cross-linker antibody to cross link Fab monomers of anti-CD44; (d) co-treatment of stimulated cells with anti CD44 mAb alone or anti-CD44v9 mAb alone suppresses PMA-induced clustering of CD44, which results in inhibition of uPA overexpression; (e) bikunin efficiently disrupts PMA-induced clustering of CD44, but does not prevent PMA-induced up regulation of CD44v isoforms containing epitope v9; and (f) after exposure to bik, approximately 150-kDa band is mainly detected with immunoprecipitation and this band is shown to be a heterodimer composed of the 110-kDa v9-containing CD44v isoforms and a 45-kDa bik receptor (bik-R). In conclusion, we provide, for the first time, evidence that the bik-R can physically interact with the CD44v isoforms containing epitope v9 and function as a repressor to down-regulate PMA stimulated uPA expression, at least in part, by preventing clustering of CD44v isoforms containing epitope v9. PMID- 11777909 TI - c-Cbl binding and ubiquitin-dependent lysosomal degradation of membrane associated Notch1. AB - Regulation of Notch1 activity is critical for cell fate decisions and differentiation of skeletal myoblasts. We have employed the skeletal myoblast cell line C2C12 to study posttranslational regulation of Notch1 protein levels during myogenesis. Although the major degradation pathway of the activated intracellular Notch1 fragment appears to involve ubiquitination and degradation by the 26 S proteasome, we provide evidence for an alternative catalytic pathway where the endogenous, transmembrane form of Notch1 is targeted to the lysosomal compartment. Immunoprecipitation analysis revealed ubiquitin-dependent accumulation of transmembrane Notch1 protein after treatment with the lysosomal inhibitor chloroquine but not after treatment with various proteasome inhibitors. This finding was supported by the observation that the transmembrane form of Notch1 was tyrosine-phosphorylated and specifically coprecipitated with the ubiquitin ligase c-Cbl. Our data suggest a regulatory mechanism down-regulating Notch1 protein levels already at the cellular surface, possibly with consequences for Notch-dependent signal transduction during terminal differentiation processes. PMID- 11777910 TI - The SANT domain of Ada2 is required for normal acetylation of histones by the yeast SAGA complex. AB - Transcription is regulated through chromatin remodeling and histone modification, mediated by large protein complexes. Histone and nucleosome interaction has been shown to be mediated by specific chromatin domains called bromodomains and chromodomains. Here we provide evidence for a similar function of two additional domains within the yeast SAGA complex, containing the histone acetyltransferase Gcn5. We have analyzed deletion and substitution mutations within Gcn5 and Ada2, an interacting protein within SAGA, and have identified substrate recognition functions within the SANT domain of Ada2 and regions of the histone acetyltransferase domain of Gcn5 that are distinct from catalytic function itself. These results suggest that histone and nucleosomal substrate recognition by SAGA involves multiple conserved domains and proteins, beyond those that have been previously identified. PMID- 11777911 TI - The crystal structure of Helicobacter pylori cysteine-rich protein B reveals a novel fold for a penicillin-binding protein. AB - Colonization of the gastric mucosa with the spiral-shaped Gram-negative proteobacterium Helicobacter pylori is probably the most common chronic infection in humans. The genomes of H. pylori strains J99 and 26695 have been completely sequenced. Functional and three-dimensional structural information is available for less than one third of all open reading frames. We investigated the function and three-dimensional structure of a member from a family of cysteine-rich hypothetical proteins that are unique to H. pylori and Campylobacter jejuni. The structure of H. pylori cysteine-rich protein (Hcp) B possesses a modular architecture consisting of four alpha/alpha-motifs that are cross-linked by disulfide bridges. The Hcp repeat is similar to the tetratricopeptide repeat, which is frequently found in protein/protein interactions. In contrast to the tetratricopeptide repeat, the Hcp repeat is 36 amino acids long. HcpB is capable of binding and hydrolyzing 6-amino penicillinic acid and 7-amino cephalosporanic acid derivatives. The HcpB fold is distinct from the fold of any known penicillin binding protein, indicating that the Hcp proteins comprise a new family of penicillin-binding proteins. The putative penicillin binding site is located in an amphipathic groove on the concave side of the molecule. PMID- 11777912 TI - Extracellular release of the glycosylphosphatidylinositol (GPI)-linked Leishmania surface metalloprotease, gp63, is independent of GPI phospholipolysis: implications for parasite virulence. AB - The major zinc metalloprotease of Leishmania (gp63), an important determinant of parasite virulence, is attached to the parasite surface via a glycosylphosphatidylinositol anchor. Here we report the spontaneous release of proteolytically active gp63 from a number of Leishmania isolates, causing cutaneous and visceral disease. To investigate the mechanism(s) of gp63 release, we transfected a gp63-deficient variant of Leishmania amazonensis with constructs expressing gp63 and various mutants thereof. Surprisingly, approximately half of wild type gp63 was found in the culture supernatant 12 h post-synthesis. Biochemical analysis of the extracellular gp63 revealed two forms of the protein, one that is released from the cell surface, and another, that apparently is directly secreted. Release of cell surface gp63 was significantly reduced when the proteolytic activity of the protein was inactivated by site-specific mutagenesis or inhibited by zinc chelation, suggesting that release involves autoproteolysis. The extracellular gp63 does not contain a glycosylphosphatidylinositol moiety or ethanolamine, indicating that phospholipolysis is not involved in the release process. Release of gp63 is also independent of glycosylation. The finding of proteolytically active, extracellular gp63 produced by multiple Leishmania isolates suggests a potential role of the extracellular enzyme in substrate degradation relevant to their survival in both the mammalian host and the insect vector. PMID- 11777913 TI - Phosphorylation of 4E-BP1 is mediated by the p38/MSK1 pathway in response to UVB irradiation. AB - In resting cells, eIF4E-binding protein 1 (4E-BP1) binds to the eukaryotic initiation factor-4E (eIF-4E), preventing formation of a functional eIF-4F complex essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 dissociates it from eIF-4E, relieving the translation block. Studies suggested that insulin- or growth factor-induced 4E-BP1 phosphorylation is mediated by phosphatidylinositol 3-kinase (PI3-kinase) and its downstream protein kinase, Akt. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E. UVB-induced phosphorylation of 4E-BP1 was blocked by p38 kinase inhibitors, PD169316 and SB202190, and MSK1 inhibitor, H89, but not by mitogen-activated protein kinase kinase inhibitors, PD98059 or U0126. The PI3-kinase inhibitor, wortmannin, did not block UVB-induced 4E-BP1 phosphorylation, but blocked both UVB- and insulin-induced activation of PI3 kinase and phosphorylation of Akt. 4E-BP1 phosphorylation was blocked in JB6 Cl 41 cells expressing a dominant negative p38 kinase or dominant negative MSK1, but not in cells expressing dominant negative ERK2, JNK1, or PI3-kinase p85 subunit. Our results suggest that UVB induces phosphorylation of 4E-BP1, leading to the functional dissociation of 4E-BP1 from eIF-4E. The p38/MSK1 pathway, but not PI3 kinase or Akt, is required for mediating the UVB-induced 4E-BP1 phosphorylation. PMID- 11777914 TI - Egg sialoglycans increase intracellular pH and potentiate the acrosome reaction of sea urchin sperm. AB - Sea urchin egg jelly (EJ) triggers sperm acrosome reaction (AR), an exocytotic event required for membrane fusion of the gametes. Purified fucose sulfate polymer (FSP) in EJ is one inducer of the AR. Binding of FSP to its receptor regulates opening of two distinct calcium channels and also elevates intracellular pH (pH(i)). EJ also contains sialic acid-rich glycans (sialoglycans (SG)) that were isolated by beta-elimination followed by DEAE chromatography. In the presence of limiting amounts of FSP, the SG fraction markedly potentiates the AR; however, by itself SG has no activity. The SG fraction increases the pH(i) of sperm without increasing intracellular Ca(2+). The SG-induced increase in pH(i) is not blocked by nifedipine or high K(+), whereas the FSP-induced pH(i) increase is sensitive to both these agents. Treatment of the SG fraction with neuraminidase or mild metaperiodate that specifically cleaves the glycerol side chain of sialic acid abolishes the AR potentiation and ability of SG to elevate pH(i). These data are the first to show that there are at least two pathways to induce sperm pH(i) increase and that egg surface sialic acid plays a role in triggering the sperm AR. PMID- 11777915 TI - The forkhead transcription factor AFX activates apoptosis by induction of the BCL 6 transcriptional repressor. AB - The activation of the AKT/protein kinase B kinases by mutation of the PTEN lipid phosphatase results in enhanced survival of a diversity of tumors. This resistance to apoptosis is partly accomplished by the inhibition of genetic programs induced by a subfamily of forkhead transcription factors including AFX. Here we describe an AFX-regulated pathway that appears to account for at least part of this apoptotic regulatory system. Cells induced to synthesize an active form of AFX die by activating the apoptotic death pathway. An analysis of genes regulated by AFX demonstrated that BCL-6, a transcriptional repressor, is up regulated approximately 4-7-fold. An examination of the BCL-6 promoter demonstrated that AFX bound to specific target sites that could activate transcription. BCL-X(L), an anti-apoptotic protein, contains potential BCL-6 target sites in its promoter. An analysis of endogenous BCL-X(L) levels in AFX expressing cells revealed enhanced down-regulation of the transcript ( approximately 1.3-1.7-fold) and protein, and BCL-6 directly binds to and suppresses the BCL-X(L) promoter. Finally, macrophages isolated from BCL-6-/- mice show enhanced survival in vitro. These results suggest that AFX regulates apoptosis in part by suppressing the levels of anti-apoptotic BCL-XL through the transcriptional repressor BCL-6. PMID- 11777916 TI - Internalized group V secretory phospholipase A2 acts on the perinuclear membranes. AB - Mammalian secretory phospholipases A(2) (sPLA(2)) have been implicated in cellular eicosanoid biosynthesis but the mechanism of their cellular action remains unknown. To elucidate the spatiotemporal dynamics of sPLA(2) mobilization and determine the site of its lipolytic action, we performed time-lapse confocal microscopic imaging of fluorescently labeled sPLA(2) acting on human embryonic kidney (HEK) 293 cells the membranes of which are labeled with a fluorogenic phospholipid, N-((6-(2,4-dinitrophenyl)amino)hexanoyl)-1-hexadecanoyl-2-(4,4 difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-sn-glycero-3 phosphoethanolamine. The Western blotting analysis of HEK293 cells treated with exogenous sPLA(2)s showed that not only the affinity for heparan sulfate proteoglycan but also other factors, such as sPLA(2) hydrolysis products or cytokines, are necessary for the internalization of sPLA(2) into HEK293 cells. Live cell imaging showed that the hydrolysis of fluorogenic phospholipids incorporated into HEK293 cell membranes was synchronized with the spatiotemporal dynamics of sPLA(2) internalization, detectable initially at the plasma membrane and then at the perinuclear region. Also, immunocytostaining showed that human group V sPLA(2) induced the translocation of 5-lipoxygenase to the nuclear envelope at which they were co-localized. Together, these studies provide the first experimental evidence that the internalized sPLA(2) acts on the nuclear envelope to provide arachidonate for other enzymes involved in the eicosanoid biosynthesis. PMID- 11777917 TI - Divergence of bacterial lipopolysaccharide pro-apoptotic signaling downstream of IRAK-1. AB - The vascular endothelium is a key target of circulating bacterial lipopolysaccharide (LPS). LPS elicits a wide array of endothelial responses, including the up-regulation of cytokines, adhesion molecules, and tissue factor, many of which are dependent on NF-kappa B activation. In addition, LPS has been demonstrated to induce endothelial apoptosis both in vitro and in vivo. Although the mechanism by which LPS activates NF-kappa B has been well elucidated, the signaling pathway(s) involved in LPS-induced apoptosis remains unknown. Using a variety of dominant negative constructs, we have identified a role for MyD88 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in mediating LPS pro apoptotic signaling in human endothelial cells. We also demonstrate that LPS induced endothelial NF-kappa B activation and apoptosis occur independent of one another. Together, these data suggest that the proximal signaling molecules involved in LPS-induced NF-kappa B activation have a requisite involvement in LPS induced apoptosis and that the pathways leading to NF-kappa B activation and apoptosis diverge downstream of IRAK-1. PMID- 11777918 TI - Characterization of the interaction between DNA gyrase inhibitor and DNA gyrase of Escherichia coli. AB - Escherichia coli DNA gyrase is comprised of two subunits, GyrA and GyrB. Previous studies have shown that GyrI, a regulatory factor of DNA gyrase activity, inhibits the supercoiling activity of DNA gyrase and that both overexpression and antisense expression of the gyrI gene suppress cell proliferation. Here we have analyzed the interaction of GyrI with DNA gyrase using two approaches. First, immunoprecipitation experiments revealed that GyrI interacts preferentially with the holoenzyme in an ATP-independent manner, although a weak interaction was also detected between GyrI and the individual GyrA and GyrB subunits. Second, surface plasmon resonance experiments indicated that GyrI binds to the gyrase holoenzyme with higher affinity than to either the GyrA or GyrB subunit alone. Unlike quinolone antibiotics, GyrI was not effective in stabilizing the cleavable complex consisting of gyrase and DNA. Further, we identified an 8-residue synthetic peptide, corresponding to amino acids (89)ITGGQYAV(96) of GyrI, which inhibits gyrase activity in an in vitro supercoiling assay. Surface plasmon resonance analysis of the ITGGQYAV-containing peptide-gyrase interaction indicated a high association constant for this interaction. These results suggest that amino acids 89--96 of GyrI are essential for its interaction with, and inhibition of, DNA gyrase. PMID- 11777920 TI - Detection, quantitation, purification, and identification of cardiac proteins S thiolated during ischemia and reperfusion. AB - We have developed methods that allow detection, quantitation, purification, and identification of cardiac proteins S-thiolated during ischemia and reperfusion. Cysteine was biotinylated and loaded into isolated rat hearts. During oxidative stress, biotin-cysteine forms a disulfide bond with reactive protein cysteines, and these can be detected by probing Western blots with streptavidin-horseradish peroxidase. S-Thiolated proteins were purified using streptavidin-agarose. Thus, we demonstrated that reperfusion and diamide treatment increased S-thiolation of a number of cardiac proteins by 3- and 10-fold, respectively. Dithiothreitol treatment of homogenates fully abolished the signals detected. Fractionation studies indicated that the modified proteins are located within the cytosol, membrane, and myofilament/cytoskeletal compartments of the cardiac cells. This shows that biotin-cysteine gains rapid and efficient intracellular access and acts as a probe for reactive protein cysteines in all cellular locations. Using Western blotting of affinity-purified proteins we identified actin, glyceraldehyde-3-phosphate dehydrogenase, HSP27, protein-tyrosine phosphatase 1B, protein kinase Calpha, and the small G-protein ras as substrates for S-thiolation during reperfusion of the ischemic rat heart. MALDI-TOF mass fingerprint analysis of tryptic peptides independently confirmed actin and glyceraldehyde-3-phosphate dehydrogenase S-thiolation during reperfusion. This approach has also shown that triosephosphate isomerase, aconitate hydratase, M-protein, nucleoside diphosphate kinase B, and myoglobin are S-thiolated during post-ischemic reperfusion. PMID- 11777919 TI - Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. AB - Tumor necrosis factor-alpha (TNF) receptor-associated factor 2 (TRAF2) is one of the major mediators of TNF receptor superfamily transducing TNF signaling to various functional targets, including activation of NF-kappa B, JNK, and antiapoptosis. We investigated how TRAF2 mediates differentially the distinct downstream signals. We now report a novel mechanism of TRAF2-mediated signal transduction revealed by an association of TRAF2 with sphingosine kinase (SphK), a lipid kinase that is responsible for the production of sphingosine 1-phosphate. We identified a TRAF2-binding motif of SphK that mediated the interaction between TRAF2 and SphK resulting in the activation of the enzyme, which in turn is required for TRAF2-mediated activation of NF-kappa B but not JNK. In addition, by using a kinase inactive dominant-negative SphK and a mutant SphK that lacks TRAF2 binding motif we show that the interaction of TRAF2 with SphK and subsequent activation of SphK are critical for prevention of apoptosis during TNF stimulation. These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis. PMID- 11777921 TI - Determination of the site-specific oligosaccharide distribution of the O-glycans attached to the porcine submaxillary mucin tandem repeat. Further evidence for the modulation of O-glycans side chain structures by peptide sequence. AB - Little is known of the degree that polypeptide sequence and the local environment modulate the structures of O-linked glycans. Toward this understanding, the site specific mono- (GalNAc-O-), di- (beta-Gal-1,3-alpha-GalNAc-O-), and trisaccharide (alpha-Fuc-1,2-beta-Gal-1,3-alpha-GalNAc-O-) distributions have been determined for 29 of the 31 O-glycosylated Ser/Thr residues in the tandem repeat domains of blood group A-negative porcine submaxillary gland mucin. The glycosylation patterns obtained from three individual animals are in agreement with earlier incomplete determinations on a pooled mucin (Gerken, T. A., Owens, C. L., and Pasumarthy, M. (1997) J. Biol. Chem. 272, 9709-9719; Gerken, T. A., Owens, C. L., and Pasumarthy, M. (1998) J. Biol. Chem. 273, 26580-26588), confirming that the addition of the peptide-linked GalNAc and its substitution by beta-1,3-Gal are sensitive to local peptide sequence in a highly reproducible manner in vivo. The present data further support earlier suggestions of an inverse correlation of the density of hydroxyamino acid residues (and by inference the density of peptide GalNAc) with the extent of substitution of the peptide-linked GalNAc by beta-1,3 Gal. This effect is highly correlated for Ser-linked glycans but not for Thr linked glycans. A similar correlation is observed with respect to the in vivo peptide GalNAc glycosylation pattern. In contrast, the addition of alpha-1,2-Fuc to beta-Gal shows no apparent correlation with hydroxyamino acid density, although a marked elevation in the fucosylation of Ser-linked glycans compared with Thr-linked glycans is observed. The above effects may represent both steric and conformational factors acting to alter the relative accessibility and activity of the glycosyltransferases toward substrate. These results demonstrate that the porcine submaxillary gland core 1 beta 3-galactosyltransferase and alpha2-fucosyltransferase exhibit unique peptide/glycopeptide sensitivities that may provide mechanisms for the modulation of O-linked side chain structures. PMID- 11777922 TI - Conformational regulation of SNARE assembly and disassembly in vivo. AB - SNAP receptor (SNARE) proteins function in intracellular trafficking by forming complexes that bridge vesicle and target membranes prior to fusion. Biochemical studies indicate that the entry of certain SNARE proteins into complexes is inhibited by intramolecular interactions that generate a closed conformation. For example, an essential N-terminal regulatory domain of the yeast plasma membrane SNARE Sso1p sequesters the C-terminal SNARE motif and prevents it from binding to its assembly partners Sec9p and Sncp. Here, we introduce mutations into Sso1p that cause it to remain constitutively open. These open mutants can functionally substitute for wild-type Sso1p protein in vivo, demonstrating that inhibition of SNARE assembly is not the essential function of the N-terminal regulatory domain. Furthermore, the open mutants suppress sec9--4, a mutation that causes a severe defect in SNARE assembly. Elevated levels of SNARE complexes are observed in cells expressing the open mutants. In the presence of sufficient Sec9p, these complexes accumulate to levels that cause severe growth defects. Similarly, overexpression of the open mutants in yeast carrying mutations in the SNARE disassembly machinery impairs growth. Our findings indicate that elevated levels of SNARE complexes can be toxic and that these levels are normally controlled by the SNARE disassembly machinery, by the limited availability of Sec9p, and by the closed conformation of Sso1p. PMID- 11777923 TI - The cytoplasmic tail of alpha 1,3-galactosyltransferase inhibits Golgi localization of the full-length enzyme. AB - It is currently under debate whether the mechanism of Golgi retention of different glycosyltransferases is determined by sequences in the transmembrane, luminal, or cytoplasmic domains or a combination of these domains. We have shown that the cytoplasmic domains of alpha1,3-galactosyltransferase (GT) and alpha1,2 fucosyltransferase (FT) are involved in Golgi localization. Here we show that the cytoplasmic tails of GT and FT are sufficient to confer specific Golgi localization. Further, we show that the expression of only the cytoplasmic tail of GT can lead to displacement or inhibition of binding of the whole transferase and that cells expressing the cytoplasmic tail of GT were not able to express full-length GT or its product, Galalpha1,3Gal. Thus, the presence of the cytoplasmic tail prevented the localization and function of full-length GT, suggesting a possible specific Golgi binding site for GT. The effect was not altered by the inclusion of the transmembrane domain. Although the transmembrane domain may act as an anchor, these data show that, for GT, only the cytoplasmic tail is involved in specific localization to the Golgi. PMID- 11777924 TI - Defective oligomerization of arylsulfatase a as a cause of its instability in lysosomes and metachromatic leukodystrophy. AB - In one of the most common mutations causing metachromatic leukodystrophy, the P426L-allele of arylsulfatase A (ASA), the deficiency of ASA results from its instability in lysosomes. Inhibition of lysosomal cysteine proteinases protects the P426L-ASA and restores the sulfatide catabolism in fibroblasts of the patients. P426L-ASA, but not wild type ASA, was cleaved by purified cathepsin L at threonine 421 yielding 54- and 9-kDa fragments. X-ray crystallography at 2.5-A resolution showed that cleavage is not due to a difference in the protein fold that would expose the peptide bond following threonine 421 to proteases. Octamerization, which depends on protonation of Glu-424, was impaired for P426L ASA. The mutation lowers the pH for the octamer/dimer equilibrium by 0.6 pH units from pH 5.8 to 5.2. A second oligomerization mutant (ASA-A464R) was generated that failed to octamerize even at pH 4.8. A464R-ASA was degraded in lysosomes to catalytically active 54-kDa intermediate. In cathepsin L-deficient fibroblasts, degradation of P426L-ASA and A464R-ASA to the 54-kDa fragment was reduced, while further degradation was blocked. This indicates that defective oligomerization of ASA allows degradation of ASA to a catalytically active 54-kDa intermediate by lysosomal cysteine proteinases, including cathepsin L. Further degradation of the 54-kDa intermediate critically depends on cathepsin L and is modified by the structure of the 9-kDa cleavage product. PMID- 11777925 TI - Overexpression of an ADP-ribosylation factor-guanine nucleotide exchange factor, BIG2, uncouples brefeldin A-induced adaptor protein-1 coat dissociation and membrane tubulation. AB - BIG2 is a guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF) family of small GTPases, which regulate membrane association of COPI and adaptor protein (AP)-1 coat protein complexes. A fungal metabolite, brefeldin A (BFA), inhibits ARF-GEFs and leads to redistribution of coat proteins from membranes to the cytoplasm and membrane tubulation of the Golgi complex and the trans-Golgi network (TGN). To investigate the function of BIG2, we examined the effects of BIG2-overexpression on the BFA-induced redistribution of ARF, coat proteins, and organelle markers. The BIG2 overexpression blocked BFA-induced redistribution from membranes of ARF1 and the AP-1 complex but not that of the COPI complex. These observations indicate that BIG2 is implicated in membrane association of AP-1, but not that of COPI, through activating ARF. Furthermore, not only BIG2 but also ARF1 and AP-1 were found as queues of spherical swellings along the BFA-induced membrane tubules emanating from the TGN. These observations indicate that BFA-induced AP-1 dissociation from TGN membranes and tubulation of TGN membranes are not coupled events and suggest that a BFA target other than ARF GEFs exists in the cell. PMID- 11777926 TI - The integration of YidC into the cytoplasmic membrane of Escherichia coli requires the signal recognition particle, SecA and SecYEG. AB - The integration of the polytopic membrane protein YidC into the inner membrane of Escherichia coli was analyzed employing an in vitro system. Upon integration of in vitro synthesized YidC, a 42-kDa membrane protected fragment was detected, which could be immunoprecipitated with polyclonal anti-YidC antibodies. The occurrence of this fragment is in agreement with the predicted topology of YidC and probably encompasses the first two transmembrane domains and the connecting 320-amino acid-long periplasmic loop. The integration of YidC was strictly dependent on the signal recognition particle and SecA. YidC could not be integrated in the absence of SecY, SecE, or SecG, suggesting that YidC, in contrast to its mitochondrial orthologue Oxa1p, cannot engage a SecYEG independent protein-conducting channel. PMID- 11777927 TI - Activation of signal transducer and activator of transcription 1 (STAT1) is not sufficient for the induction of STAT1-dependent genes in endothelial cells. Comparison of interferon-gamma and oncostatin M. AB - We compared human endothelial cell (EC) responses to interferon-gamma (IFN gamma) and oncostatin M (OnM), cytokines that utilize Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Both cytokines cause phosphorylation of Tyr residue 701 and Ser residue 727 of STAT1, as shown by immunoblotting. Both activate DNA binding of STAT1 homodimers, shown by electrophoretic mobility shift assay. However, only IFN gamma increases expression of three STAT1-dependent gene products examined, namely transporter associated with antigen processing-1 (TAP1), interferon regulatory factor-1 (IRF1), and class I major histocompatibility complex (MHC) protein, as demonstrated by immunoblotting. Only IFN gamma increases TAP1 transcription assessed by reporter gene assay. OnM pretreatment or co-treatment does not inhibit IFN gamma responses. Interestingly, IFN gamma activation of STAT1 is considerably more long-lived than that produced by OnM. To determine whether duration is functionally significant, we transduced EC with a chimeric receptor containing extracellular domains of platelet-derived growth factor receptor beta and intracellular regions of gp130, the signaling subunit of the OnM receptor, mutated to prevent binding of the tyrosine phosphatase SHP-2. Addition of platelet-derived growth factor to such transduced cells produces STAT1 activation that is comparable in magnitude and duration to that caused by IFN gamma, but still fails to induce TAP1, IRF1, or class I MHC molecules. OnM also activates STAT1 but not transcription of STAT1-dependent genes in HepG2 cells. Transient transfection of HepG2 cells with a STAT-defective mouse IFN gamma receptor failed to complement the OnM STAT signal. We conclude that STAT1 activation is necessary but not sufficient for induction of transcription of IFN gamma-responsive genes. However, signals provided by IFN gamma other than STAT1 activation cannot be provided in trans to complement the response to OnM. PMID- 11777928 TI - AT1 receptor mutant lacking heterotrimeric G protein coupling activates the Src Ras-ERK pathway without nuclear translocation of ERKs. AB - Angiotensin II (Ang II) type 1 receptors (AT1Rs) activate tyrosine kinases, including Src. Whether or not tyrosine kinase activation by AT1R occurs independently of heterotrimeric G protein coupling and, if so, the cellular function of such a mechanism are unknown. To address these questions, we used an AT1aR intracellular second loop mutant, which lacks heterotrimeric G protein coupling (AT1a-i2m). Surprisingly, Ang II-induced Src activation was preserved in AT1a-i2m, which was not attenuated by inhibiting protein kinase C and Ca(2+) or by inhibiting Galpha(i) or Galpha(q) in CHO-K1 cells. By contrast, Ang II-induced Src activation was abolished in a C-terminally truncated AT1a-(1--309), where Ang II-induced inositol phosphate response was preserved. Ang II activates ERKs via a Src-Ras-dependent mechanism in AT1a-i2m. ERKs activated by AT1a-i2m phosphorylate their cytoplasmic targets, including p90(RSK), but fail to translocate into the nucleus or to cause cell proliferation. Ang II-induced nuclear translocation of ERKs by wild type AT1aR was inhibited by overexpression of nuclear exportin Crm 1, while that by AT1a-i2m was restored by leptomycin B, an inhibitor of Crm-1. In summary, while Src and ERKs are activated by Ang II even without heterotrimeric G protein coupling, the carboxyl terminus of the AT1 receptor is required for activation of Src. Interestingly, ERKs activated by heterotrimeric G protein independent mechanisms fail to phosphorylate nuclear targets due to lack of inhibition of Crm-1-induced nuclear export of ERKs. These results suggest that heterotrimeric G protein-dependent and -independent signaling mechanisms play distinct roles in Ang II-mediated cellular responses. PMID- 11777929 TI - Nerve growth factor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomyelinase. AB - Binding of nerve growth factor (NGF) to the p75 neurotrophin receptor (p75) in cultured hippocampal neurons has been reported to cause seemingly contrasting effects, namely ceramide-dependent axonal outgrowth of freshly plated neurons, versus Jun kinase (Jnk)-dependent cell death in older neurons. We now show that the apoptotic effects of NGF in hippocampal neurons are observed only from the 2nd day of culture onward. This switch in the effect of NGF is correlated with an increase in p75 expression levels and increasing levels of ceramide generation as the cultures mature. NGF application to neuronal cultures from p75(exonIII-/-) mice had no effect on ceramide levels and did not affect neuronal viability. The neutral sphingomyelinase inhibitor, scyphostatin, inhibited NGF-induced ceramide generation and neuronal death, whereas hippocampal neurons cultured from acid sphingomyelinase(-/-) mice were as susceptible to NGF-induced death as wild type neurons. The acid ceramidase inhibitor, (1S,2R)-d-erythro-2-(N-myristoylamino)-1 phenyl-1-propanol, enhanced cell death, supporting a role for ceramide itself and not a downstream lipid metabolite. Finally, scyphostatin inhibited NGF-induced Jnk phosphorylation in hippocampal neurons. These data indicate an initiating role of ceramide generated by neutral sphingomyelinase in the diverse neuronal responses induced by binding of neurotrophins to p75. PMID- 11777930 TI - BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs. AB - BRCA1, a breast and ovarian cancer susceptibility gene, has been implicated in gene regulation. Previous studies demonstrate that BRCA1 induces GADD45, a p53 regulated and stress-inducible gene that plays an important role in cellular response to DNA damage. However, the mechanism(s) by which BRCA1 regulates GADD45 remains unclear. In this report, we have shown that BRCA1 activation of the GADD45 promoter is mediated through the OCT-1 and CAAT motifs located at the GADD45 promoter region. Site-directed mutations of both OCT-1 and CAAT motifs abrogate induction of the GADD45 promoter by BRCA1. Both OCT-1 and CAAT motifs are able to confer BRCA1 inducibility in a non-related minimal promoter. Physical associations of BRCA1 protein with transcription factors Oct-1 and NF-YA, which directly bind to the OCT-1 and CAAT motifs, are established by biotin streptavidin pull-down and coimmunoprecipitation assays. Such protein interactions are required for interaction of BRCA1 with the GADD45 promoter because either immunodepletion of Oct-1 and NF-YA proteins or mutations in the OCT-1 and CAAT motifs disrupt BRCA1 binding to the GADD45 promoter. These findings indicate that BRCA1 can up-regulate its targeted genes through protein protein interactions and provide a novel mechanism by which BRCA1 participates in transcriptional regulation. PMID- 11777931 TI - Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. AB - Recent data have demonstrated that vascular endothelial growth factor (VEGF) is expressed by subsets of neurons, coincident with angiogenesis within the developing cerebral cortex. Here we investigate the characteristics of VEGF expression by neurons and test the hypothesis that VEGF may serve both paracrine and autocrine functions in the developing central nervous system. To begin to address these questions, we assayed expression of VEGF and one of its potential receptors, Flk-1 (VEGFR-2), in the embryonic mouse forebrain and embryonic cortical neurons grown in vitro. Both VEGF and Flk-1 are present in subsets of post-mitotic neurons in vivo and in vitro. Moreover, VEGF levels are up-regulated in neuronal cultures subjected to hypoxia, consistent with our previous results in vivo. While the abundance of Flk-1 is unaffected by hypoxia, the receptor exhibits a higher level of tyrosine phosphorylation, as do downstream signaling kinases, including extracellular signal-regulated protein kinase, p90RSK and STAT3a, demonstrating activation of the VEGF pathway. These same signaling components also exhibited higher tyrosine phosphorylation levels in response to exogenous addition of rVEGFA(165). This activation was diminished in the presence of specific inhibitors of Flk-1 function and agents that sequester VEGF, resulting in a dose-dependent increase in apoptosis in these neuronal cultures. Further, inhibition of MEK resulted in increased apoptosis, while inhibition of phosphatidylinositol 3-kinase had no appreciable affect. In addition to the novel function for VEGF that we describe in neuronal survival, neuronal VEGF also affected the organization and differentiation of brain endothelial cells in a three-dimensional culture paradigm, consistent with its more traditional role as a vascular agent. Thus, our in vitro data support a role for neuronal VEGF in both paracrine and autocrine signaling in the maintenance of neurons and endothelia in the central nervous system. PMID- 11777932 TI - Arrestin variants display differential binding characteristics for the phosphorylated N-formyl peptide receptor carboxyl terminus. AB - The phosphorylation-dependent binding of arrestins to cytoplasmic domains of G protein-coupled receptors (GPCRs) is thought to be a crucial step in receptor desensitization. In some GPCR systems, arrestins have also been demonstrated to be involved in receptor internalization, resensitization, and the activation of signaling cascades. The objective of the current study was to examine binding interactions of members of the arrestin family with the formyl peptide receptor (FPR), a member of the GPCR family of receptors. Peptides representing the unphosphorylated and phosphorylated carboxyl terminus of the FPR were synthesized and bound to polystyrene beads via a biotin/streptavidin interaction. Using fluorescein-conjugated arrestins, binding interactions between arrestins and the bead-bound FPR carboxyl terminus were analyzed by flow cytometry. Arrestin-2 and arrestin-3 bound to the FPR carboxyl-terminal peptide in a phosphorylation dependent manner, with K(d) values in the micromolar range. Binding of visual arrestin, which binds rhodopsin with high selectivity, was not observed. Arrestin 2-(1--382) and arrestin-3-(1--393), truncated mutant forms of arrestin that display phosphorylation-independent binding to intact receptors, were also observed to bind the bead-bound FPR terminus in a phosphorylation-dependent manner, but with much greater affinity than the full-length arrestins, yielding K(d) values in the 5--50 nm range. Two additional arrestin mutants, which are full-length but display phosphorylation-independent binding to intact GPCRs, were evaluated for their binding affinity to the FPR carboxyl terminus. Whereas the single point mutant, arrestin-2 R169E, displayed an affinity similar to that of the full-length arrestins, the triple point mutant, arrestin-2 I386A/V387A/F388A, displayed an affinity more similar to that of the truncated forms of arrestin. The results suggest that the carboxyl terminus of arrestin is a critical determinant in regulating the binding affinity of arrestin for the phosphorylated domains of GPCRs. PMID- 11777933 TI - A Myc-associated zinc finger protein-related factor binding site is required for the deregulation of c-myc expression by the immunoglobulin heavy chain gene enhancers in Burkitt's lymphoma. AB - The deregulation of expression of the c-myc gene in Burkitt's lymphoma results from the translocation that links one c-myc allele to one of the immunoglobulin genes. This physical linkage promotes interactions between c-myc and immunoglobulin gene regulatory elements that affect c-myc transcription initiation and elongation. We have located a region in the c-myc promoter that is required for the complete activation by the immunoglobulin heavy chain gene enhancer. This regulatory element contains a core sequence, GGGAGG, similar to the GA box recognized by the transcription factor Myc-associated zinc finger protein (MAZ). UV cross-link analysis indicated that the mass of this protein did not correspond to that of MAZ, suggesting that a protein related to but distinct from MAZ bound to this site. Mutation of this regulatory element resulted in a loss of promoter activity induced by the immunoglobulin heavy chain gene enhancer. This site was also required for the c-myc promoter shift from P2 to P1. In vivo footprinting revealed that this site was occupied on the translocated c myc allele but not on the untranslocated allele. Taken together, these findings suggest that this regulatory element is required for the full activation of c-myc promoter activity by the immunoglobulin heavy chain gene enhancer. PMID- 11777934 TI - Characterization of two unusual guanylyl cyclases from dictyostelium. AB - Guanylyl cyclase A (GCA) and soluble guanylyl cyclase (sGC) encode GCs in Dictyostelium and have a topology similar to 12-transmembrane and soluble adenylyl cyclase, respectively. We demonstrate that all detectable GC activity is lost in a cell line in which both genes have been inactivated. Cell lines with one gene inactivated were used to characterize the other guanylyl cyclase (i.e. GCA in sgc(minus sign) null cells and sGC in gca(minus sign) null cells). Despite the different topologies, the enzymes have many properties in common. In vivo, extracellular cAMP activates both enzymes via a G-protein-coupled receptor. In vitro, both enzymes are activated by GTPgammaS (K(a) = 11 and 8 microm for GCA and sGC, respectively). The addition of GTPgammaS leads to a 1.5-fold increase of V(max) and a 3.5-fold increase of the affinity for GTP. Ca(2+) inhibits both GCA and sGC with K(i) of about 50 and 200 nm, respectively. Other biochemical properties are very different; GCA is expressed mainly during growth and multicellular development, whereas sGC is expressed mainly during cell aggregation. Folic acid and cAMP activate GCA maximally about 2.5-fold, whereas sGC is activated about 8-fold. Osmotic stress strongly stimulates sGC but has no effect on GCA activity. Finally, GCA is exclusively membrane-bound and is active mainly with Mg(2+), whereas sGC is predominantly soluble and more active with Mn(2+). PMID- 11777935 TI - Mutational analysis of the subunit C (Vma5p) of the yeast vacuolar H+-ATPase. AB - Subunit C is a V(1) sector subunit found in all vacuolar H(+)-ATPases (V-ATPases) that may be part of the peripheral stalk connecting the peripheral V(1) sector with the membrane-bound V(0) sector of the enzyme (Wilkens, S., Vasilyeva, E., and Forgac, M. (1999) J. Biol. Chem. 274, 31804--31810). To elucidate subunit C function, we performed random and site-directed mutagenesis of the yeast VMA5 gene. Site-directed mutations in the most highly conserved region of Vma5p, residues 305--325, decreased catalytic activity of the V-ATPase by up to 48% without affecting assembly. A truncation mutant (K360stop) identified by random mutagenesis suggested a small region near the C terminus of the protein (amino acids 382--388) might be important for subunit stability. Site-directed mutagenesis revealed that three aromatic amino acids in this region (Tyr-382, Phe 385, and Tyr-388) in addition to four other conserved aromatic amino acids (Phe 260, Tyr-262, Phe-296, Phe-300) are essential for stable assembly of V(1) with V(0), although alanine substitutions at these positions support some activity in vivo. Surprisingly, three mutations (F260A, Y262A, and F385A) greatly decrease the stability of the V-ATPase in vitro but increase its k(cat) for ATP hydrolysis and proton transport by at least 3-fold. The peripheral stalk of V-ATPases must balance the stability essential for productive catalysis with the dynamic instability involved in regulation; these three mutations may perturb that balance. PMID- 11777936 TI - Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion. AB - The Rho GTPase and Fyn tyrosine kinase have been implicated previously in positive control of keratinocyte cell-cell adhesion. Here, we show that Rho and Fyn operate along the same signaling pathway. Endogenous Rho activity increases in differentiating keratinocytes and is required for both Fyn kinase activation and increased tyrosine phosphorylation of beta- and gamma-catenin, which is associated with the establishment of keratinocyte cell-cell adhesion. Conversely, expression of constitutive active Rho is sufficient to promote cell-cell adhesion through a tyrosine kinase- and Fyn-dependent mechanism, trigger Fyn kinase activation, and induce tyrosine phosphorylation of beta- and gamma-catenin and p120ctn. The positive effects of activated Rho on cell-cell adhesion are not induced by an activated Rho mutant with defective binding to the serine/threonine PRK2/PKN kinases. Endogenous PRK2 kinase activity increases with keratinocyte differentiation, and, like activated Rho, increased PRK2 activity promotes keratinocyte cell-cell adhesion and induces tyrosine phosphorylation of beta- and gamma-catenin and Fyn kinase activation. Thus, these findings reveal a novel role of Fyn as a downstream mediator of Rho in control of keratinocyte cell-cell adhesion and implicate the PRK2 kinase, a direct Rho effector, as a link between Rho and Fyn activation. PMID- 11777937 TI - Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. AB - The retinoblastoma (Rb) tumor suppressor controls cellular proliferation, survival, and differentiation and is functionally inactivated by mutations or hyperphosphorylation in most human cancers. Although activation of endogenous Rb is thought to provide an effective approach to suppress cell proliferation, long term inhibition of apoptosis by active Rb may have detrimental consequences in vivo. To directly test these paradigms, we targeted phosphorylation-resistant constitutively active Rb alleles, Rb Delta Ks, to the mouse mammary gland. Pubescent transgenic females displayed reduced ductal elongation and cell proliferation at the endbuds. Post-puberty transgenic mice exhibited precocious cellular differentiation and beta-casein expression and extended survival of the mammary epithelium with a moderate but specific effect on the expression of E2F1, IGF1R alpha, and phospho-protein kinase B/AKT. Remarkably, approximately 30% Rb Delta K transgenic females developed focal hyperplastic nodules, and approximately 7% exhibited full-blown mammary adenocarcinomas within 15 mo. Expression of the Rb Delta K transgene in these mammary tumors was reduced greatly. Our results suggest that transient activation of Rb induces cancer by extending cell survival and that the dual effects of Rb on cell proliferation and apoptosis impose an inherent caveat to the use of the Rb pathway for long-term cancer therapy. PMID- 11777938 TI - Polo boxes and Cut23 (Apc8) mediate an interaction between polo kinase and the anaphase-promoting complex for fission yeast mitosis. AB - The fission yeast plo1(+) gene encodes a polo-like kinase, a member of a conserved family of kinases which play multiple roles during the cell cycle. We show that Plo1 kinase physically interacts with the anaphase-promoting complex (APC)/cyclosome through the noncatalytic domain of Plo1 and the tetratricopeptide repeat domain of the subunit, Cut23. A new cut23 mutation, which specifically disrupts the interaction with Plo1, results in a metaphase arrest. This arrest can be rescued by high expression of Plo1 kinase. We suggest that this physical interaction is crucial for mitotic progression by targeting polo kinase activity toward the APC. PMID- 11777939 TI - Mechanisms through which Sos-1 coordinates the activation of Ras and Rac. AB - Signaling from receptor tyrosine kinases (RTKs)* requires the sequential activation of the small GTPases Ras and Rac. Son of sevenless (Sos-1), a bifunctional guanine nucleotide exchange factor (GEF), activates Ras in vivo and displays Rac-GEF activity in vitro, when engaged in a tricomplex with Eps8 and E3b1-Abi-1, a RTK substrate and an adaptor protein, respectively. A mechanistic understanding of how Sos-1 coordinates Ras and Rac activity is, however, still missing. Here, we demonstrate that (a) Sos-1, E3b1, and Eps8 assemble into a tricomplex in vivo under physiological conditions; (b) Grb2 and E3b1 bind through their SH3 domains to the same binding site on Sos-1, thus determining the formation of either a Sos-1-Grb2 (S/G) or a Sos-1-E3b1-Eps8 (S/E/E8) complex, endowed with Ras- and Rac-specific GEF activities, respectively; (c) the Sos-1 Grb2 complex is disrupted upon RTKs activation, whereas the S/E/E8 complex is not; and (d) in keeping with the previous result, the activation of Ras by growth factors is short-lived, whereas the activation of Rac is sustained. Thus, the involvement of Sos-1 at two distinct and differentially regulated steps of the signaling cascade allows for coordinated activation of Ras and Rac and different duration of their signaling within the cell. PMID- 11777941 TI - Structural requirements for localization and activation of protein kinase C mu (PKC mu) at the Golgi compartment. AB - We here describe the structural requirements for Golgi localization and a sequential, localization-dependent activation process of protein kinase C (PKC) mu involving auto- and transphosphorylation. The structural basis for Golgi compartment localization was analyzed by confocal microscopy of HeLa cells expressing various PKC mu-green fluorescent protein fusion proteins costained with the Golgi compartment-specific markers p24 and p230. Deletions of either the NH(2)-terminal hydrophobic or the cysteine region, but not of the pleckstrin homology or the acidic domain, of PKC mu completely abrogated Golgi localization of PKC mu. As an NH(2)-terminal PKC mu fragment was colocalized with p24, this region of PKC mu is essential and sufficient to mediate association with Golgi membranes. Fluorescence recovery after photobleaching studies confirmed the constitutive, rapid recruitment of cytosolic PKC mu to, and stable association with, the Golgi compartment independent of activation loop phosphorylation. Kinase activity is not required for Golgi complex targeting, as evident from microscopical and cell fractionation studies with kinase-dead PKC mu found to be exclusively located at intracellular membranes. We propose a sequential activation process of PKC mu, in which Golgi compartment recruitment precedes and is essential for activation loop phosphorylation (serines 738/742) by a transacting kinase, followed by auto- and transphosphorylation of NH(2)-terminal serine(s) in the regulatory domain. PKC mu activation loop phosphorylation is indispensable for substrate phosphorylation and thus PKC mu function at the Golgi compartment. PMID- 11777940 TI - Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons. AB - In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta 1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha 6 beta 4 integrin. These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy. PMID- 11777942 TI - Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. AB - We have identified a novel human karyopherin (Kap) beta family member that is related to human Crm1 and the Saccharomyces cerevisiae protein, Msn5p/Kap142p. Like other known transport receptors, this Kap binds specifically to RanGTP, interacts with nucleoporins, and shuttles between the nuclear and cytoplasmic compartments. We report that interleukin enhancer binding factor (ILF)3, a double stranded RNA binding protein, associates with this Kap in a RanGTP-dependent manner and that its double-stranded RNA binding domain (dsRBD) is the limiting sequence required for this interaction. Importantly, the Kap interacts with dsRBDs found in several other proteins and binding is blocked by double-stranded RNA. We find that the dsRBD of ILF3 functions as a novel nuclear export sequence (NES) in intact cells, and its ability to serve as an NES is dependent on the expression of the Kap. In digitonin-permeabilized cells, the Kap but not Crm1 stimulated nuclear export of ILF3. Based on the ability of this Kap to mediate the export of dsRNA binding proteins, we named the protein exportin-5. We propose that exportin-5 is not an RNA export factor but instead participates in the regulated translocation of dsRBD proteins to the cytoplasm where they interact with target mRNAs. PMID- 11777943 TI - Cutting edge: Th2 response induction by dendritic cells: a role for CD40. AB - We investigated the influence of dendritic cell (DC) CD40 expression on Th2 and Th1 development by in vivo transfer of Ag-pulsed bone marrow-derived DC generated from wild-type (WT) or CD40(-/-) mice. Contrary to expectation, CD40(-/-) DC primed with Ag that inherently induce a Th2 response (soluble egg Ag from Schistosoma mansoni) failed to induce a Th2 response or any compensatory Th1 response, whereas CD40(-/-)DC primed with Ag that inherently induce a Th1 response (Propionibacterium acnes) generated a competent Th1 response. Thus, DC expression of CD40 is a prerequisite for initiation of Th2, but not Th1, responses by these Ag. Consistent with this, CD154(-/-) mice, unlike WT mice, failed to mount a Th2 response when directly injected with schistosome eggs but mounted a normal Th1 response after challenge with P. acnes. CD40-CD154 interaction can therefore play a major role in Th2 response induction. PMID- 11777944 TI - Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly. AB - Ag recognition by T lymphocytes induces immune synapse formation and recruitment of signaling molecules into a lipid raft. Cbp/PAG is a Csk-associated membrane adapter protein exclusively localized in a lipid raft. We identified NHERF/EBP50 as a Cbp-binding molecule, which connects the membrane raft and cytoskeleton by binding to both Cbp through its PDZ domain and ezrin-radixin-moesin through the C terminus. Overexpression of Cbp reduced the mobility of the raft on the cell surface of unstimulated T cells and prevented synapse formation and subsequent T cell activation, whereas a mutant incapable of EBP50 binding restored both synapse formation and activation. These results suggest that anchoring of lipid raft to the cytoskeleton through Cbp-EBP50-ezrin-radixin-moesin assembly regulates membrane dynamism for synapse formation and T cell activation. PMID- 11777945 TI - Indirect IL-4 pathway in type 1 immunity. AB - Recall Ag-specific IL-4 was detected in the spleen and in the blood, but not in lymph nodes of mice in which polarized type 1 immunity was induced. This IL-4 was not produced by T cells, but soluble factors secreted by the recall Ag-activated T cells, including IL-3, triggered cells of the innate immune system, primarily mast cells, to secrete IL-4. This notion has profound implications for immunodiagnostics: the detection of apparently recall Ag-specific IL-4 does not necessarily reflect the presence of Th2 or Th0 memory T cells with long-term cytokine commitment as is of interest for assessing adoptive immunity. We found that in vivo the indirect IL-4 pathway did not suffice to trigger IgE isotype switching, but promoted IgG1 production and inhibited type 1 T cell differentiation. Therefore, the indirect IL-4 pathway can explain partial type 2 immune response phenotypes in vivo in face of unipolar Th1 T cell immunity. The representation of mast cells in different tissues may explain why immune responses in certain organs are more type 2 biased. Therefore, the indirect pathway of IL-4 production represents a novel type of interaction between the innate and the adoptive immune system that can contribute to the outcome of host defense and immune pathology. PMID- 11777946 TI - Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. AB - Members of the Toll-like receptor (TLR) family mediate dorsoventral patterning and cellular adhesion in insects as well as immune responses to microbial products in both insects and mammals. TLRs are characterized by extracellular leucine-rich repeat domains and an intracellular signaling domain that shares homology with cytoplasmic sequences of the mammalian IL-1 receptor and plant disease resistance genes. Ten human TLRs have been cloned as well as RP105, a protein similar to TLR4 but lacking the intracellular signaling domain. However, only five TLRs have described functions as receptors for bacterial products (e.g., LPS, lipoproteins). To identify potential sites of action, we used quantitative real-time RT-PCR to examine systematically the expression of mRNAs encoding all known human TLRs, RP105, and several other proteins important in TLR functions (e.g., MD-1, MD-2, CD14, MyD88). Most tissues tested expressed at least one TLR, and several expressed all (spleen, peripheral blood leukocytes). Analysis of TLR expression in fractionated primary human leukocytes (CD4(+), CD8(+), CD19(+), monocytes, and granulocytes) indicates that professional phagocytes express the greatest variety of TLR mRNAs although several TLRs appear more restricted to B cells, suggesting additional roles for TLRs in adaptive immunity. Monocyte-like THP-1 cells regulate TLR mRNA levels in response to a variety of stimuli including phorbol esters, LPS, bacterial lipoproteins, live bacteria, and cytokines. Furthermore, addition of Escherichia coli to human blood ex vivo caused distinct changes in TLR expression, suggesting that important roles exist for these receptors in the establishment and resolution of infections and inflammation. PMID- 11777947 TI - Potent CD4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF. AB - Virus-specific CD4(+) T cell responses have been shown to play a critical role in controlling HIV-1 replication. Candidate HIV-1 vaccines should therefore elicit potent CD4(+) as well as CD8(+) T cell responses. In this report we investigate the ability of plasmid GM-CSF to augment CD4(+) T cell responses elicited by an HIV-1 gp120 DNA vaccine in mice. Coadministration of a plasmid expressing GM-CSF with the gp120 DNA vaccine led to only a marginal increase in gp120-specific splenocyte CD4(+) T cell responses. However, immunization with a bicistronic plasmid that coexpressed gp120 and GM-CSF under control of a single promoter led to a dramatic augmentation of vaccine-elicited CD4(+) T cell responses, as measured by both cellular proliferation and ELISPOT assays. This augmentation of CD4(+) T cell responses was selective, since vaccine-elicited Ab and CD8(+) T cell responses were not significantly changed by the addition of GM-CSF. A 100 fold lower dose of the gp120/GM-CSF bicistronic DNA vaccine was required to elicit detectable gp120-specific splenocyte proliferative responses compared with the monocistronic gp120 DNA vaccine. Consistent with these findings, i.m. injection of the gp120/GM-CSF bicistronic DNA vaccine evoked a more extensive cellular infiltrate at the site of inoculation than the monocistronic gp120 DNA vaccine. These results demonstrate that bicistronic DNA vaccines containing GM CSF elicit remarkably potent CD4(+) T cell responses and suggest that optimal Th cell priming requires the precise temporal and spatial codelivery of Ag and GM CSF. PMID- 11777948 TI - The receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins. AB - Previous studies have shown that human heat shock protein (hsp) 60 elicits a strong proinflammatory response in cells of the innate immune system with CD14, Toll-like receptor (TLR) 2, and TLR4 as mediators of signaling, but probably not of binding. In the present study, we directly demonstrate binding of hsp60 to the macrophage surface and find the binding receptor for hsp60 different from the previously described common receptor for several other heat shock proteins, including hsp70, hsp90, and gp96. Fluorescence-labeled human hsp60 bound to cell surfaces of the murine macrophage lines J774 A.1 and RAW264.7 and to mouse bone marrow-derived macrophages. By flow cytometry, we could demonstrate for the first time that hsp60 binding to macrophages occurred at submicromolar concentrations, is saturable, and can be competed by unlabeled hsp60, but not by unrelated proteins, thus confirming the classic characteristics of specific ligand-receptor interactions. Binding of hsp60 at 4 degrees C was followed by endocytosis at 37 degrees C. Hsp60 binding to macrophages could not be competed by excess hsp70, hsp90, or gp96, all of which share the alpha(2)-macroglobulin receptor as binding site. Hsp60 binding occurred in the absence of surface TLR4. However, no cytokine response was induced by hsp60 in TLR4-deficient macrophages. We conclude that hsp60 binds to a stereo-specific receptor on macrophages, and that different surface molecules are engaged in binding and signal transduction. Furthermore, the binding site for hsp60 is separate from the common receptor for hsp70, hsp90, and gp96, which suggests an independent role of hsp60 as danger Ag and in immunoregulation. PMID- 11777949 TI - I-kappa B kinase beta is critical for B cell proliferation and antibody response. AB - The NF-kappaB proteins are critical in the regulation of the immune and inflammatory response. Stimulation of the NF-kappaB pathway leads to increases in I-kappaB kinase beta (IKKbeta) kinase activity to result in the enhanced phosphorylation and degradation of I-kappaB and the translocation of the NF kappaB proteins from the cytoplasm to the nucleus. In this study, a dominant negative IKKbeta mutant expressed from the IgH promoter was used to generate transgenic mice to address the role of IKKbeta on B cell function. Although these transgenic mice were defective in activating the NF-kappaB pathway in B cells, they exhibited no defects in B lymphocyte development or basal Ig levels. However, they exhibited defects in the cell cycle progression and proliferation of B cells in response to treatment with LPS, anti-CD40, and anti-IgM. Furthermore, selective defects in the production of specific Ig subclasses in response to both T-dependent and T-independent Ags were noted. These results suggest that IKKbeta is critical for the proliferation of B cells and the control of some aspects of the humoral response. PMID- 11777950 TI - Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin. AB - The success of stem cell transplantation depends on the ability of i.v. infused stem cells to engraft the bone marrow, a process referred to as homing. Efficient homing requires migration of CD34(+) cells across the bone marrow endothelium, most likely through the intercellular junctions. In this study, we show that loss of vascular endothelial (VE)-cadherin-mediated endothelial cell-cell adhesion increases the permeability of monolayers of human bone marrow endothelial cells (HBMECs) and stimulates the transendothelial migration of CD34(+) cells in response to stromal cell-derived factor-1alpha. Stromal cell-derived factor 1alpha-induced migration was dependent on VCAM-1 and ICAM-1, even in the absence of VE-cadherin function. Cross-linking of ICAM-1 to mimic the leukocyte endothelium interaction induced actin stress fiber formation but did not induce loss of endothelial integrity, whereas cross-linking of VCAM-1 increased the HBMEC permeability and induced gaps in the monolayer. In addition, VCAM-1 mediated gap formation in HBMEC was accompanied by and dependent on the production of reactive oxygen species. These data suggest that modulation of VE cadherin function directly affects the efficiency of transendothelial migration of CD34(+) cells and that activation of ICAM-1 and, in particular, VCAM-1 plays an important role in this process through reorganization of the endothelial actin cytoskeleton and by modulating the integrity of the bone marrow endothelium through the production of reactive oxygen species. PMID- 11777951 TI - IL-2 and related cytokines can promote T cell survival by activating AKT. AB - The regulated elimination of T cells serves to maintain normal immune function and prevents autoimmune responses. IL-2 family cytokines play an important role in controlling the survival of immature and mature T cells. These molecules activate the protein kinase, AKT/PKB. AKT has been shown to transduce an antiapoptotic signal in numerous cell types. In this study, we show that an active form of AKT can protect T cells from apoptosis following growth factor withdrawal and that IL-2 family cytokines can promote T cell survival by activating this kinase. We also provide evidence that AKT does not block death receptor-mediated killing of lymphocytes. These data suggest that AKT may serve as a common signaling element by which members of the IL-2 family of cytokines promote T cell survival. PMID- 11777952 TI - Fractalkine is expressed by smooth muscle cells in response to IFN-gamma and TNF alpha and is modulated by metalloproteinase activity. AB - Fractalkine/CX3C-chemokine ligand 1 is expressed as a membrane-spanning adhesion molecule that can be cleaved from the cell surface to produce a soluble chemoattractant. Within the vasculature, fractalkine is known to be generated by endothelial cells, but to date there are no reports describing its expression by smooth muscle cells (SMC). In this study we demonstrate that IFN-gamma and TNF alpha, but not IL-1beta, cooperate synergistically to induce fractalkine mRNA and protein expression in cultured aortic SMC. We also report the release of functional, soluble fractalkine from the membranes of stimulated SMC. This release is inhibited by the zinc metalloproteinase inhibitor batimastat, resulting in the accumulation of membrane-associated fractalkine on the SMC surface. Therefore, an SMC-derived metalloproteinase activity is involved in fractalkine shedding. While soluble fractalkine present in SMC-conditioned medium is capable of inducing calcium transients in cells expressing the fractalkine receptor (CX3CR1), blocking experiments using neutralizing Abs reveal that it can be inactivated without affecting the chemotactic activity of SMC-conditioned media on monocytes. However, membrane-bound fractalkine plays a major role in promoting adhesion of monocytic cells to activated SMC. This fractalkine-mediated adhesion is further enhanced in the presence of batimastat, indicating that shedding of fractalkine from the cell surface down-regulates the adhesive properties of SMC. Hence, during vascular inflammation, the synergistic induction of fractalkine by IFN-gamma and TNF-alpha together with its metalloproteinase mediated cleavage may finely control the recruitment of monocytes to SMC within the blood vessel wall. PMID- 11777953 TI - Peptide specificity of thymic selection of CD4+CD25+ T cells. AB - The CD4(+)CD25(+) regulatory T cells can be found in the thymus, but their need to undergo positive and negative selection has been questioned. Instead, it has been hypothesized that CD4(+)CD25(+) cells mature following TCR binding to MHC backbone, to low abundant MHC/peptide complexes, or to class II MHC loaded with peripheral autoantigens. In all these circumstances, processes that are distinct from positive and negative selection would govern the provenance of CD4(+)CD25(+) cells in the thymus. By comparing the development of CD4(+)CD25(-) and CD4(+)CD25(+) cells in mice expressing class II MHC molecules bound with one or many peptide(s), we show that the CD4(+)CD25(+) cells appear during natural selection of CD4(+) T cells. The proportion of CD4(+)CD25(+) cells in the population of CD4(+) thymocytes remains constant, and their total number reflects the complexity of selecting class II MHC/peptide complexes. Hence, thymic development of CD4(+)CD25(+) cells does not exclusively depend on the low density, high-affinity MHC/peptide complexes or thymic presentation of peripheral self-Ags, but, rather, these cells are selected as a portion of the natural repertoire of CD4(+) T cells. Furthermore, while resistant to deletion mediated by endogenous superantigen(s), these cells were negatively selected on class II MHC/peptide complexes. We postulate that while the CD4(+)CD25(+) thymocytes are first detectable in the thymic medulla, their functional commitment occurs in the thymic cortex. PMID- 11777954 TI - Elimination of porcine hemopoietic cells by macrophages in mice. AB - The difficulty in achieving donor hemopoietic engraftment across highly disparate xenogeneic species barriers poses a major obstacle to exploring xenograft tolerance induction by mixed chimerism. In this study, we observed that macrophages mediate strong rejection of porcine hemopoietic cells in mice. Depletion of macrophages with medronate-encapsulated liposomes (M-liposomes) markedly improved porcine chimerism, and early chimerism in particular, in sublethally irradiated immunodeficient and lethally irradiated immunocompetent mice. Although porcine chimerism in the peripheral blood and spleen of M-liposome treated mice rapidly declined after macrophages had recovered and became indistinguishable from controls by wk 5 post-transplant, the levels of chimerism in the marrow of these mice remained higher than those in control recipients at 8 wks after transplant. These results suggest that macrophages that developed in the presence of porcine chimerism were not adapted to the porcine donor and that marrow-resident macrophages did not phagocytose porcine cells. Moreover, M liposome treatment had no effect on the survival of porcine PBMC injected into the recipient peritoneal cavity, but was essential for the migration and relocation of these cells into other tissues/organs, such as spleen, bone marrow, and peripheral blood. Together, our results suggest that murine reticuloendothelial macrophages, but not those in the bone marrow and peritoneal cavity, play a significant role in the clearance of porcine hemopoietic cells in vivo. Because injection of M-liposomes i.v. mainly depletes splenic macrophages and liver Kupffer cells, the spleen and/or liver are likely the primary sites of porcine cell clearance in vivo. PMID- 11777955 TI - The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB. AB - Many studies have shown that FcgammaRIIB is a negative regulator of B cell receptor signaling, and even though FcgammaRIIB is expressed through all developmental stages of the B cell lineage, its involvement in pre-B cell receptor (pre-BCR) signaling has not been examined. To investigate FcgammaRIIB function at the pre-B cell stage, we have established pre-BCR positive pre-B cell lines from normal mice and FcgammaRIIB-deficient mice, named PreBR and Fcgamma(-/ )PreBR, respectively. These cell lines are able to differentiate into immature B cells in vitro by removal of IL-7. In PreBR, apoptosis was moderately induced by F(ab')(2) anti-mu Ab, but not by intact anti-mu Ab. Phosphorylation of SH2 containing inositol 5-phosphatase (SHIP) and Dok, which are involved in FcgammaRIIB signaling, was induced by anti-mu cross-linking in PreBR. In contrast, apoptosis was strongly induced by both the F(ab')(2) and intact anti-mu Abs in Fcgamma(-/-)PreBR, and the level of phosphorylation of SHIP or Dok was much lower in Fcgamma(-/-)PreBR than those observed in PreBR. Restoration of FcgammaRIIB to Fcgamma(-/-)PreBR followed by anti-mu cross-linking blocked severe apoptosis, and up-regulated SHIP and Dok phosphorylation. The results demonstrate that FcgammaRIIB negatively regulates pre-BCR-mediated signaling for apoptosis. PMID- 11777956 TI - A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. AB - The regulation of hematopoietic stem cell (HSC) homeostasis is not well understood. We screened for genetic polymorphisms that were linked to differences between mouse strains in the numbers of long-term reconstituting HSCs or restricted progenitors in the bone marrow. AKR/J mice had significantly higher frequencies and numbers of both HSCs and restricted progenitors in their bone marrow than C57BL/Ka-Thy-1.1 mice. The C57BL/Ka-Thy-1.1 alleles were partially dominant. A locus on chromosome 17, including the H-2 complex, was significantly linked to the frequency of long-term self-renewing HSCs but showed no evidence of linkage to the frequency of restricted progenitors. Conversely, a chromosome 1 locus exhibited suggestive linkage to restricted progenitor frequencies but was not linked to HSC frequency. This demonstrates that there are distinct genetic determinants of the frequencies of HSCs and restricted progenitors in vivo. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. This suggests that to affect HSC frequencies, the product(s) of this locus likely depend on interactions with unlinked modifying loci. PMID- 11777957 TI - The BCR/ABL transgene causes abnormal NK cell differentiation and can be found in circulating NK cells of advanced phase chronic myelogenous leukemia patients. AB - NK cells from the blood of chronic myelogenous leukemia (CML) patients are progressively decreased in number as the disease progresses from chronic phase to blast crisis. We hypothesize that BCR/ABL may be directly responsible by interfering with NK cell differentiation. CD34(+)HLA-DR(+) cells from CML patients were studied for their capacity to differentiate into NK cells. The NK cell cloning frequency was significantly decreased from CML CD34(+)HLA-DR(+) cells compared with cells from normal donors, yet CD34(+)HLA-DR(+) cells gave rise to BCR/ABL(+) NK cells in some patients. This finding prompted us to further investigate circulating NK cells from the blood of CML patients. CD56(+)CD3(-) NK cells were sorted from CML patients and examined by fluorescence in situ hybridization (FISH). In contrast to chronic phase CML, significant numbers of NK cells from advanced phase CML patients were BCR/ABL(+), whereas T cells were always BCR/ABL(-) regardless of the disease stage. To test the effects of BCR/ABL as the sole genetic abnormality, BCR/ABL was transduced into umbilical cord blood CD34(+) cells, and NK development was studied. p210-enhanced green fluorescence protein-transduced cells gave rise to significantly decreased numbers of NK cells compared with enhanced green fluorescence protein transduction alone. In addition, the extrinsic addition of BCR/ABL-transduced autologous CD34(+) cells suppressed the NK cell differentiation of normal umbilical cord blood CD34(+)CD38(-) cells. This study provides the first evidence that BCR/ABL is responsible for the altered differentiation of NK cells and that the NK cell lineage can be involved with the malignant clone in advanced stage CML. PMID- 11777958 TI - Can the low-avidity self-specific T cell repertoire be exploited for tumor rejection? AB - Can self-specific T cells that have escaped intrathymic deletion be exploited to generate antitumor immunity? To determine whether antitumor immunity to a self-Ag for which central tolerance exists can be generated, a mouse model is used in which a fragment of the influenza nucleoprotein (NP) is expressed as a transgene under the control of the H-2K promoter in C57BL/10 mice (B10NP mice). In these mice an oligoclonal population of NP-specific T cells escapes thymic and peripheral deletion and can be activated upon immunization. The main hallmark of these self-specific CD8(+) T cells is diminished avidity for the pertinent MHC/peptide complex. We show in this study that intranasal infection with influenza virus can stimulate low-avidity NP-specific T cells to recognize and destroy NP-expressing microtumors in the lung, but not NP-expressing tumors growing s.c. Only a memory NP-specific CD8(+) T cell response can suppress the growth of an s.c. growing NP-expressing tumor. This delay in tumor growth is associated with a dramatic increase in the number of circulating NP-specific CD8(+) T cells. In addition, cultured memory NP-specific T cells require approximately 100-fold less Ag to induce NP-specific lysis than primary T cells, consistent with the observation that memory T cells have an increased avidity due to affinity maturation. Finally, during an NP-specific memory response, substantial numbers of low-avidity NP-specific T cells can be recovered from s.c. growing tumors. Together, these findings indicate that, when only a low-avidity repertoire is available to generate antitumor immunity, the best strategy may be to enhance memory responses. PMID- 11777959 TI - Ox40 costimulation enhances the development of T cell responses induced by dendritic cells in vivo. AB - Dendritic cells (DCs) are bone marrow-derived APCs that display unique properties aimed at stimulating naive T cells. Several members of the TNF/TNFR families have been implicated in T cell functions. In this study, we examined the role that Ox40 costimulation might play on the ability of DCs to regulate CD4(+) and CD8(+) T cell responses in vivo. Administration of anti-mouse Ox40 mAb enhanced the Th response induced by immunization with Ag-pulsed DCs, and introduced a bias toward a Th1 immune response. However, anti-Ox40 treatment enhanced the production of Th2 cytokines in IFN-gamma(-/-) mice after immunization with Ag-pulsed DCs, suggesting that the production of IFN-gamma during the immune response could interfere with the development of Th2 lymphocytes induced by DCs. Coadministration of anti-Ox40 with DCs during Ag rechallenge enhanced both Th1 and Th2 responses induced during a primary immunization with DCs, and did not reverse an existing Th2 response. This suggests that Ox40 costimulation amplifies an ongoing immune response, regardless of Th differentiation potential. In an OVA TCR class II-restricted adoptive transfer system, anti-Ox40 treatment greatly enhanced the level of cytokine secretion per Ag-specific CD4(+) T cell induced by immunization with DCs. In an OVA-TCR class I-restricted adoptive transfer system, administration of anti-Ox40 strongly enhanced expansion, IFN-gamma secretion, and cytotoxic activity of Ag-specific CD8(+) T cells induced by immunization with DCs. Thus, by enhancing immune responses induced by DCs in vivo, the Ox40 pathway might be a target for immune intervention in therapeutic settings that use DCs as Ag-delivery vehicles. PMID- 11777960 TI - UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. AB - The UL16-binding proteins (ULBPs) are a novel family of MHC class I-related molecules that were identified as targets of the human CMV glycoprotein, UL16. We have previously shown that ULBP expression renders a relatively resistant target cell sensitive to NK cytotoxicity, presumably by engaging NKG2D, an activating receptor expressed by NK and other immune effector cells. In this study we show that NKG2D is the ULBP counterstructure on primary NK cells and that its expression is up-regulated by IL-15 stimulation. Soluble forms of ULBPs induce marked protein tyrosine phosphorylation, and activation of the Janus kinase 2, STAT5, extracellular signal-regulated kinase, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signal transduction pathways. ULBP-induced activation of Akt and extracellular signal-regulated kinase and ULBP induced IFN-gamma production are blocked by inhibitors of PI 3-kinase, consistent with the known binding of PI 3-kinase to DAP10, the membrane-bound signal transducing subunit of the NKG2D receptor. While all three ULBPs activate the same signaling pathways, ULBP3 was found to bind weakly and to induce the weakest signal. In summary, we have shown that NKG2D is the ULBP counterstructure on primary NK cells and for the first time have identified signaling pathways that are activated by NKG2D ligands. These results increase our understanding of the mechanisms by which NKG2D activates immune effector cells and may have implications for immune surveillance against pathogens and tumors. PMID- 11777961 TI - Sustained expression of the novel EBV-induced zinc finger gene, ZNFEB, is critical for the transition of B lymphocyte activation to oncogenic growth transformation. AB - EBV is a human tumor virus that infects and establishes latency in the majority of humans worldwide. In vitro, EBV growth transforms primary B lymphocytes into lymphoblastoid cell lines with high efficiency. We have used cDNA subtraction cloning to identify cellular target genes required for growth transformation and identified a new C(2)H(2) (Kruppel-type) zinc finger gene, ZNF(EB), that is trans activated early following EBV infection. In this study, we characterize ZNF(EB), including its intronless locus, and human and mouse protein variants. The gene is transiently expressed during normal lymphocyte activation, and its expression is sustained in EBV-positive but not EBV-negative B cell lines. There is limited expression in nonhemopoietic tissues. Its critical role in the growth transformation of B lineage cells is indicated by the abrogation of transformation with antisense strategies. ZNF(EB) maps to chromosome 18q12, a region with mutations in numerous, predominantly hemopoietic malignancies. PMID- 11777962 TI - Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. AB - CD11b(+)Gr-1(+) myeloid suppressor cells (MSC) accumulate in lymphoid organs under conditions of intense immune stress where they inhibit T and B cell function. We recently described the generation of immortalized MSC lines that provide a homogeneous source of suppressor cells for dissecting the mechanism of suppression. In this study we show that the MSC lines potently block in vitro proliferation of T cells stimulated with either mitogen or antigenic peptide, with as few as 3% of MSC cells causing complete suppression. Inhibition of mitogenic and peptide-specific responses is not associated with a loss in IL-2 production or inability to up-modulate the early activation markers, CD69 and CD25, but results in direct impairment of the three IL-2R signaling pathways, as demonstrated by the lack of Janus kinase 3, STAT5, extracellular signal-regulated kinase, and Akt phosphorylation in response to IL-2. Suppression is mediated by and requires NO, which is secreted by MSC in response to signals from activated T cells, including IFN-gamma and a contact-dependent stimulus. Experiments with inducible NO synthase knockout mice demonstrated that the inhibition of T cell proliferation by CD11b(+)Gr-1(+) cells in the spleens of immunosuppressed mice is also dependent upon NO, indicating that the MSC lines accurately represent their normal counterparts. The distinctive capacity of MSC to generate suppressive signals when encountering activated T cells defines a specialized subset of myeloid cells that most likely serve a regulatory function during times of heightened immune activity. PMID- 11777963 TI - Alpha 4 integrin signaling activates phosphatidylinositol 3-kinase and stimulates T cell adhesion to intercellular adhesion molecule-1 to a similar extent as CD3, but induces a distinct rearrangement of the actin cytoskeleton. AB - Dynamic regulation of beta(2) integrin-dependent adhesion is critical for a wide array of T cell functions. We previously showed that binding of high-affinity alpha(4)beta(1) integrins to VCAM-1 strengthens alpha(L)beta(2) integrin-mediated adhesion to ICAM-1. In this study, we compared beta(2) integrin-mediated adhesion of T cells to ICAM-1 under two different functional contexts: alpha(4) integrin signaling during emigration from blood into tissues and CD3 signaling during adhesion to APCs and target cells. Cross-linking either alpha(4) integrin or CD3 on Jurkat T cells induced adhesion to ICAM-1 of comparable strength. Adhesion was dependent on phosphatidylinositol (PI) 3-kinase but not p44/42 mitogen-activated protein kinase (extracellular regulated kinase 1/2), because it was inhibited by wortmannin and LY294002 but not U0126. These data suggest that PI 3-kinase is a ubiquitous regulator of beta(2) integrin-mediated adhesion. A distinct morphological change consisting of Jurkat cell spreading and extension of filopodia was induced by alpha(4) integrin signaling. In contrast, CD3 induced radial rings of cortical actin polymerization. Inhibitors of PI 3-kinase and extracellular regulated kinase 1/2 did not affect alpha(4) integrin-induced rearrangement of the actin cytoskeleton, but treatment with ionomycin, a Ca(2+) ionophore, modulated cell morphology by reducing filopodia and promoting lamellipodia formation. Qualitatively similar morphological and adhesive changes to those observed with Jurkat cells were observed following alpha(4) integrin or CD3 stimulation of human peripheral blood T cells. PMID- 11777964 TI - Reduced expression of Bcl-2 in CD8+ T cells deficient in the IL-15 receptor alpha chain. AB - Mice that lack IL-15 or the IL-15R alpha-chain (IL-15Ralpha) are deficient in peripheral CD8(+), but not in CD4(+), T cells. This CD8(+) T cell-specific deficiency has now been investigated further by characterization of a new strain of IL-15Ralpha(-/-) mice. The adult mutant mice exhibited a specific reduction in the percentage of CD8-single positive TCR(high) thymocytes. The expression of Bcl 2 was reduced in both CD8(+) thymocytes and naive T cells of the mutant animals, and the susceptibility of these cells to death was increased. Memory CD8(+) cells were profoundly deficient in IL-15Ralpha(-/-)mice, and the residual memory-like CD8(+) cells contained a high percentage of dead cells and failed to up-regulate Bcl-2 expression compared with naive CD8(+) cells. Moreover, exogenous IL-15 both up-regulated the level of Bcl-2 in and reduced the death rate of wild-type and mutant CD8(+) T cells activated in vitro. These results indicate that IL-15 and IL-15Ralpha regulate the expression of Bcl-2 in CD8(+) T cells at all developmental stages. The reduced Bcl-2 content in CD8(+) cells might result in survival defect and contribute to the reduction of CD8(+) cells in IL-15Ralpha(-/ )mice. PMID- 11777965 TI - IL-1 beta enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): a mechanism for T cell-independent DC activation. AB - CD40 ligand (CD40L) is a membrane-bound molecule expressed by activated T cells. CD40L potently induces dendritic cell (DC) maturation and IL-12p70 secretion and plays a critical role during T cell priming in the lymph nodes. IFN-gamma and IL 4 are required for CD40L-mediated cytokine secretion, suggesting that T cells are required for optimal CD40L activity. Because CD40L is rapidly up-regulated by non T cells during inflammation, CD40 stimulation may also be important at the primary infection site. However, a role for T cells at the earliest stages of infection is unclear. The present study demonstrates that the innate immune cell derived cytokine, IL-1beta, can increase CD40L-induced cytokine secretion by monocyte-derived DC, CD34(+)-derived DC, and peripheral blood DC independently of T cell-derived cytokines. Furthermore, IL-1beta is constitutively produced by monocyte-derived DC and monocytes, and is increased in response to intact Escherichia coli or CD40L, whereas neither CD34(+)-derived DC nor peripheral blood DC produce IL-1beta. Finally, DC activated with CD40L and IL-1beta induce higher levels of IFN-gamma secretion by T cells compared with DC activated with CD40L alone. Therefore, IL-1beta is the first non-T cell-derived cytokine identified that enhances CD40L-mediated activation of DC. The synergy between CD40L and IL-1beta highlights a potent, T cell-independent mechanism for DC activation during the earliest stages of inflammatory responses. PMID- 11777966 TI - Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum. AB - CD1d1 is a member of a family of lipid Ag-presenting molecules. The cellular ligands associated with CD1d1 were isolated and characterized by biochemical means as an approach to elucidate the mechanism by which CD1 molecules assemble in vivo. Natural ligands of mouse CD1d1 included cellular phosphatidylinositol and phosphatidylinositol-glycans that are synthesized in the endoplasmic reticulum. Further biochemical data revealed that the two CD1d1 mutants, one defective in recycling from-and-to the plasma membrane and the other in efficiently negotiating the secretory pathway, associated with phosphatidylinositol. Thus phosphatidylinositol associated with CD1d1 in the early secretory pathway. Phosphatidylinositol also associated with CD1d1 in Pig-A deficient cells that are defective in the first glycosylation step of glycosylphosphatidylinositol biosynthesis. Moreover, cellular phosphatidylinositol-glycans are not Valpha14Jalpha15 natural T cell Ags. Therefore, we predict that cellular lipids occlude the hydrophobic Ag-binding groove of CD1 during assembly until they are exchanged for a glycolipid Ag(s) within the recycling compartment for display on the plasma membrane. In this manner, cellular lipids might play a chaperone-like role in the assembly of CD1d1 in vivo, akin to the function of invariant chain in MHC class II assembly. PMID- 11777967 TI - Multiple pathways of TWEAK-induced cell death. AB - TWEAK, a recently identified member of the TNF family, is expressed on IFN-gamma stimulated monocytes and induces cell death in certain tumor cell lines. In this study, we characterized the TWEAK-induced cell death in several tumor cell lines that exhibited distinct features. Although the TWEAK-induced cell death in Kym-1 cells was indirectly mediated by TNF-alpha and was inhibited by cycloheximide, the TWEAK-induced cell death in HSC3 cells or IFN-gamma-treated HT-29 cells was not inhibited by anti-TNF-alpha mAb or cycloheximide, suggesting a direct triggering of cell death via TWEAK receptor in the latter cell lines. The TWEAK induced apoptosis in HSC3 cells and IFN-gamma-treated HT-29 cells was associated with caspase-8 and caspase-3 activation. Although a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, inhibited the TWEAK-induced cell death in HSC3 cells, it rather sensitized HT-29 cells to TWEAK-induced cell death by necrosis. This necrosis was abrogated by lysosomal proteinase inhibitors, particularly a cathepsin B inhibitor, [L-3-trans (propylcarbamoyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline methyl ester. During the process of TWEAK-induced necrosis, cathepsin B was released from lysosome to cytosol. Although DR3 has been reported to be a receptor for TWEAK, all TWEAK sensitive tumor cell lines used in this study did not express DR3 at either protein or mRNA level, but did bind CD8-TWEAK specifically. These results indicated that TWEAK could induce multiple pathways of cell death, including both caspase-dependent apoptosis and cathepsin B-dependent necrosis, in a cell type specific manner via TWEAK receptor(s) distinct from DR3. PMID- 11777968 TI - CD40 signaling in B cells regulates the expression of the Pim-1 kinase via the NF kappa B pathway. AB - The ability of CD40 signaling to regulate B cell growth, survival, differentiation, and Ig class switching involves many changes in gene expression. Using cDNA expression arrays and Northern blotting, we found that CD40 signaling increased the mRNA levels for pim-1, a protooncogene that encodes a serine/threonine protein kinase. Subsequent experiments showed that CD40 engagement also increased both Pim-1 protein levels and Pim-1 kinase activity in B cells. We then investigated the signaling pathways by which CD40 regulates Pim 1 expression and found that CD40 up-regulates Pim-1 primarily via the activation of NF-kappaB. Inhibiting the activation of NF-kappaB, either by treating cells with a chemical inhibitor, BAY11-7082, or by inducibly expressing a superrepressor form of IkappaBalpha, significantly impaired the ability of CD40 to increase Pim-1 protein levels. Because Pim-1 expression is associated with cell proliferation and survival, we asked whether this correlated with the ability of CD40 signaling to prevent anti-IgM-induced growth arrest in the WEHI 231 murine B cell line, a model for Ag-induced clonal deletion. We found that the anti-IgM-induced growth arrest in WEHI-231 cells correlated with a substantial decrease in Pim-1 levels. In contrast, culturing WEHI-231 cells with either anti CD40 Abs or with the B cell mitogen LPS, both of which prevent the anti-IgM induced growth arrest, also prevented the rapid decline in Pim-1 levels. This suggests that Pim-1 could regulate the survival and proliferation of B cells. PMID- 11777969 TI - Transient disruption of autocrine TGF-beta signaling leads to enhanced survival and proliferation potential in single primitive human hemopoietic progenitor cells. AB - Hemopoietic stem cells (HSCs) are maintained at relative quiescence by the balance between the positive and negative regulatory factors that stimulate or inhibit their proliferation. Blocking the action of negative regulatory factors may provide a new approach for inducing HSCs into proliferation. A variety of studies have suggested that TGF-beta negatively regulates cell cycle progression of HSCs. In this study, a dominant negatively acting mutant of TGF-beta type II receptor (TbetaRIIDN) was transiently expressed in HSCs by using adenoviral vector-mediated gene delivery, such that the effects of disrupting the autocrine TGF-beta signaling in HSCs can be directly examined at a single cell level. Adenoviral vectors allowing the expression of TbetaRIIDN and green fluorescence protein in the same CD34(+)CD38(-)Lin(-) cells were constructed. Overexpression of TbetaRIIDN specifically disrupted TGF-beta-mediated signaling. Autocrine TGF beta signaling in CD34(+)CD38(-)Lin(-) cells was studied in single cell assays under serum-free conditions. Transient blockage of autocrine TGF-beta signaling in CD34(+)CD38(-)Lin(-) cells enhanced their survival. Furthermore, the overall proliferation potential and proliferation kinetics in these cells were significantly enhanced compared with the CD34(+)CD38(-)Lin(-) cells expressing green fluorescence protein alone. Therefore, we have successfully blocked the autocrine TGF-beta-negative regulatory loop of primitive hemopoietic progenitor cells. PMID- 11777970 TI - Activated human T cells accomplish MHC class II expression through T cell specific occupation of class II transactivator promoter III. AB - Activated human T cells express HLA-DR, HLA-DQ, and HLA-DP on their surface, but the regulation and functioning of MHC class II molecules in T lymphocytes are poorly understood. Because the MHC class II transactivator (CIITA) is essential for MHC class II expression, we have investigated transcriptional activation of CIITA in activated T cells. In this study, we show that in human activated CD4(+) T cells, CIITA promoter III (CIITA-PIII) drives the expression of CIITA. The in vivo genomic footprint analysis revealed activated T cell-specific occupation of CIITA-PIII. Subsequent EMSA analysis of several promoter regions showed differences in banding pattern among activated T cells, naive T cells, primary B cells, and Raji B cells. Activating response element (ARE)-1 is shown to interact with the acute myeloid leukemia 2 transcription factor in nuclear extracts derived from both T and B cells. Interestingly, the acute myeloid leukemia 3 transcription factor was bound in nuclear extracts of T cells only. The ARE-2 sequence is able to bind CREB/activating transcription factor family members in both T and B cells. In addition, a yet unidentified Ets family member was found to interact with site C in activated T cells, whereas in B cells site C was bound by PU.1 and Pip/IFN regulatory factor 4/IFN consensus sequence binding protein for activated T cells. In Jurkat T cells, both ARE-1 and ARE-2 are crucial for CIITA-PIII activity, similar to Raji B cells. The differential banding pattern in in vivo genomic footprinting and transcription factor binding at the ARE-1 and site C between T cells and B cells probably reflects differences in CIITA-PIII activation pathways employed by these cell types. PMID- 11777971 TI - Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages. AB - Cartilaginous fish (e.g., sharks) are derived from the oldest vertebrate ancestor having an adaptive immune system, and thus are key models for examining MHC evolution. Previously, family studies in two shark species showed that classical class I (UAA) and class II genes are genetically linked. In this study, we show that proteasome genes LMP2 and LMP7, shark-specific LMP7-like, and the TAP1/2 genes are linked to class I/II. Functional LMP7 and LMP7-like genes, as well as multiple LMP2 genes or gene fragments, are found only in some sharks, suggesting that different sets of peptides might be generated depending upon inherited MHC haplotypes. Cosmid clones bearing the MHC-linked classical class I genes were isolated and shown to contain proteasome gene fragments. A non-MHC-linked LMP7 gene also was identified on another cosmid, but only two exons of this gene were detected, closely linked to a class I pseudogene (UAA-NC2); this region probably resulted from a recent duplication and translocation from the functional MHC. Tight linkage of proteasome and class I genes, in comparison with gene organizations of other vertebrates, suggests a primordial MHC organization. Another nonclassical class I gene (UAA-NC1) was detected that is linked neither to MHC nor to UAA-NC2; its high level of sequence similarity to UAA suggests that UAA-NC1 also was recently derived from UAA and translocated from MHC. These data further support the principle of a primordial class I region with few class I genes. Finally, multiple paternities in one family were demonstrated, with potential segregation distortions. PMID- 11777972 TI - Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. AB - Human (h)Langerin/CD207 is a C-type lectin of Langerhans cells (LC) that induces the formation of Birbeck granules (BG). In this study, we have cloned a cDNA encoding mouse (m)Langerin. The predicted protein is 66% homologous to hLangerin with conservation of its particular features. The organization of human and mouse Langerin genes are similar, consisting of six exons, three of which encode the carbohydrate recognition domain. The mLangerin gene maps to chromosome 6D, syntenic to the human gene on chromosome 2p13. mLangerin protein, detected by a mAb as a 48-kDa species, is abundant in epidermal LC in situ and is down regulated upon culture. A subset of cells also expresses mLangerin in bone marrow cultures supplemented with TGF-beta. Notably, dendritic cells in thymic medulla are mLangerin-positive. By contrast, only scattered cells express mLangerin in lymph nodes and spleen. mLangerin mRNA is also detected in some nonlymphoid tissues (e.g., lung, liver, and heart). Similarly to hLangerin, a network of BG form upon transfection of mLangerin cDNA into fibroblasts. Interestingly, substitution of a conserved residue (Phe(244) to Leu) within the carbohydrate recognition domain transforms the BG in transfectant cells into structures resembling cored tubules, previously described in mouse LC. Our findings should facilitate further characterization of mouse LC, and provide insight into a plasticity of dendritic cell organelles which may have important functional consequences. PMID- 11777974 TI - NK cell inhibitory receptor Ly-49C residues involved in MHC class I binding. AB - Mouse NK cells express Ly-49 receptors specific for classical MHC class I molecules. Several of the Ly-49 receptors have been characterized in terms of function and ligand specificity. However, the only Ly-49 receptor-ligand interaction previously described in detail is that between Ly-49A and H-2D(d), as studied by point mutations in the ligand and the crystal structure of the co complex of these molecules. It is not known whether other Ly-49 receptors bind MHC class I in a similar manner as Ly-49A. Here we have studied the effect of mutations in Ly-49C on binding to the MHC class I molecules H-2K(b), H-2D(b), and H-2D(d). The MHC class I molecules were used as soluble tetramers to stain transiently transfected 293T cells expressing the mutated Ly-49C receptors. Three of nine mutations in Ly-49C led to loss of MHC class I binding. The three Ly-49C mutations that affected MHC binding correspond to Ly-49A residues that are in contact or close to H-2D(d) in the co-crystal, demonstrating that MHC class I binding by Ly-49C is dependent on residues in the same area as that used by Ly 49A for ligand contacts. PMID- 11777975 TI - Urokinase-type plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection. AB - Urokinase-type plasminogen activator (uPA)(-/-) mice cannot mount protective host defenses during infection with the opportunistic yeast Cryptococcus neoformans (52D). Because effective host defense against C. neoformans requires specific immune responses and the generation of type 1 (T1) cytokines, we determined how the absence of uPA impacts these processes. Wild-type (WT) and uPA(-/-) mice were inoculated with C. neoformans. Macrophage antifungal activity was assessed histologically, T lymphocyte responses in vivo and proliferation in vitro were quantified, and cytokine concentrations were determined by ELISA. uPA(-/-) macrophages have impaired antimicrobial activity. Regional lymph nodes of infected uPA(-/-) mice contained fewer cells than WT, suggesting impaired T cell proliferation in response to the pathogen in vivo. In vitro, uPA(-/-) T lymphocytes had impaired proliferative responses to C. neoformans rechallenge compared with WT. Infected WT mice generated T1 cytokines in the lung, characterized by high levels of IFN-gamma and IL-12. uPA(-/-) mice had decreased levels of IFN-gamma and IL-12, and increased IL-5, a type 2 cytokine. In the absence of uPA, the cytokine profile of regional lymph nodes shifted from a T1 pattern characterized by IFN-gamma and IL-2 to a weak, nonpolarized response. We conclude that in the absence of uPA, lymphocyte proliferative responses are diminished, and mice fail to generate protective T1 cytokines, resulting in impaired antimicrobial activity. This study provides novel evidence that uPA is a critical modulator of immune responses and of immune cell effector functions in vivo. PMID- 11777976 TI - Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung. AB - Toll-like receptors (TLRs) have been implicated in the regulation of host responses to microbial Ags. This study characterizes the role of TLR4 in the innate immune response to intrapulmonary administration of Haemophilus influenzae in the mouse. Two different strains of mice efficiently cleared aerosolized H. influenzae concurrent with a brisk elaboration of IL-1beta, IL-6, TNF-alpha, macrophage-inflammatory protein (MIP)-1alpha, and MIP-2 in bronchoalveolar lavage and a corresponding mobilization of intrapulmonary neutrophils. Congenic strains of mice deficient in TLR4 demonstrated a substantial delay in clearance of H. influenzae with diminished IL-1beta, IL-6, TNF-alpha, MIP-1alpha, and MIP-2 in bronchoalveolar lavage and a notable absence of intrapulmonary neutrophils. In TLR4-expressing animals, but not TLR4-deficient animals, TNF-alpha and MIP-1alpha expression was up-regulated in epithelial cells of the conducting airway in response to H. influenzae which was preceded by an apparent activation of the NF kappaB pathway in these cells based on the findings of decreased overall IkappaB and an increase in its phosphorylated form. This study demonstrates a critical role of TLR4 in mediating an effective innate immune response to H. influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response. PMID- 11777977 TI - The bacterial peptide N-formyl-Met-Leu-Phe inhibits killing of Staphylococcus epidermidis by human neutrophils in fibrin gels. AB - To study human neutrophil (polymorphonuclear leukocyte (PMN)) migration and killing of bacteria in an environment similar to that found in inflamed tissues in vivo, we have used fibrin gels. Fibrin gels (1500 microm thick) containing Staphylococcus epidermidis were formed in Boyden-type chemotaxis chambers. PMN migrated < 300 microm into these gels in 6 h and did not kill S. epidermidis when the gels contained heat-inactivated serum, C5-deficient serum, a streptococcal peptidase specific for a fragment of cleaved C5 (C5a), or anti-C5aR IgG. In contrast, in gels containing normal human serum, PMN migrated approximately 1000 microm into the gels in 4 h and into the full thickness of the gels in 6 h, and killed 90% of S. epidermidis in 6 h. fMLP reduced PMN migration into fibrin gels and allowed S. epidermidis to increase by approximately 300% in 4 h, whereas leukotriene B(4) stimulated PMN to migrate the full thickness of the gels and to kill 80% of S. epidermidis in 4 h. We conclude that both complement opsonization and C5a-stimulated chemotaxis are required for PMN bacterial killing in fibrin gels, and that fMLP inhibits PMN bactericidal activity in fibrin gels. The latter finding is surprising and suggests that in the presence of fibrin fMLP promotes bacterial virulence. PMID- 11777978 TI - Activation of the mitogen-activated protein kinase signaling pathway is instrumental in determining the ability of Mycobacterium avium to grow in murine macrophages. AB - Of the two common morphotypes of Mycobacterium avium, designated smooth transparent (SmT) or smooth opaque (SmO), the SmO morphotype is avirulent, whereas the SmT morphotype is virulent. The role of the host macrophage in determining these different virulence phenotypes was analyzed using an in vitro model of macrophage infection. Initial studies confirmed previous reports of the increased ability of the SmT bacteria to grow in macrophages; this increased virulence correlated with reduced induction of inflammatory cytokines. Examination of the response of the mitogen-activated protein kinase (MAPK) pathway following infection with either morphotype revealed that all three members of the MAPK pathway were activated. Pharmacologic inhibition of either the extracellular signal-regulated kinase (ERK) or p38(MAPK) pathways resulted in distinct consequences for the growth of the two morphotypes. In particular, inhibition of the p38(MAPK) resulted in attenuated growth of the SmT morphotype, which correlated with reduced PGE(2) production. Inhibition of cyclooxygenase 2 by indomethacin also inhibited growth of SmT, substantiating the role for PGE(2) in promoting the growth of SmT. In contrast, SmO induction of the ERK pathway was increased compared with the SmT morphotype, and inhibition of ERK resulted in decreased TNF-alpha synthesis and enhanced SmO growth. Pharmacologic inhibitors of the MAPK pathway were present for only the first 4 h of infection and yet had consequences for bacterial growth at 7 days. Therefore, the data suggest that induction of the MAPK pathway during uptake of bacteria is instrumental in determining the eventual fate of the bacteria. PMID- 11777979 TI - Progression of armed CTL from draining lymph node to spleen shortly after localized infection with herpes simplex virus 1. AB - We have examined the generation of CTL immunity immediately after localized footpad infection with herpes simplex virus 1 (HSV-1) using three coordinated in vivo T cell tracking methodologies. Tetrameric MHC class I containing the immunodominant peptide from HSV-1 glycoprotein B (gB) showed that after infection the proportion of Ag-specific T cells peaked at day 5 within draining popliteal lymph nodes and 2 days later in the spleen. Preferential expression of the activation marker CD25 by tetramer-positive cells in draining popliteal nodes but not spleen suggested that gB-specific T cells were initially activated within the lymph node. In vivo cytotoxicity assays showed that Ag-specific effector cells were present within the draining lymph nodes as early as day 2 after infection, with a further 2-day lag before detection in the spleen. Consistent with the very early arming of effector CTL in the draining lymph node, adoptive transfer of CFSE-labeled gB-specific transgenic T cells showed that they had undergone one to four rounds of cell division by day 2 after infection. In contrast, proliferating T cells were first detected in appreciable numbers in the spleen on day 4, at which time they had undergone extensive cell division. These data demonstrate that HSV-1-specific T cells are rapidly activated and armed within draining lymph nodes shortly after localized HSV-1 infection. This is followed by their dissemination to other compartments such as the spleen, where they further proliferate in an Ag-independent fashion. PMID- 11777980 TI - IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro. AB - Recent data show that proinflammatory stimuli may modify significantly ion transport in the airway epithelium and therefore the properties of the airway surface fluid. We have studied the effect of IL-4, a cytokine involved in the pathogenesis of asthma, on transepithelial ion transport in the human bronchial epithelium in vitro. Incubation of polarized bronchial epithelial cells with IL-4 for 6-48 h causes a marked inhibition of the amiloride-sensitive Na(+) channel as measured in short circuit current experiments. On the other hand, IL-4 evokes a 2 fold increase in the current activated by a cAMP analog, which reflects the activity of the cystic fibrosis transmembrane conductance regulator (CFTR). Similarly, IL-4 enhances the response to apical UTP, an agonist that activates Ca(2+)-dependent Cl(-) channels. These effects are mimicked by IL-13 and blocked by an antagonist of IL-4Ralpha. RT-PCR experiments show that IL-4 elicits a 7 fold decrease in the level of the gamma amiloride-sensitive Na(+) channel mRNA, one of the subunits of the amiloride-sensitive Na(+) channel, and an increase in CFTR mRNA. Our data suggest that IL-4 may favor the hydration of the airway surface by decreasing Na(+) absorption and increasing Cl(-) secretion. This could be required to fluidify the mucus, which is hypersecreted during inflammatory conditions. On the other hand, the modifications of ion transport could also affect the ion composition of airway surface fluid. PMID- 11777981 TI - CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. AB - Oxidative stress from ozone (O(3)) exposure augments airway neutrophil recruitment and chemokine production. We and others have shown that severe and sudden asthma is associated with airway neutrophilia, and that O(3) oxidative stress is likely to augment neutrophilic airway inflammation in severe asthma. However, very little is known about chemokines that orchestrate oxidative stress induced neutrophilic airway inflammation in vivo. To identify these chemokines, three groups of BALB/c mice were exposed to sham air, 0.2 ppm O(3), or 0.8 ppm O(3) for 6 h. Compared with sham air, 0.8 ppm O(3), but not 0.2 ppm O(3), induced pronounced neutrophilic airway inflammation that peaked at 18 h postexposure. The 0.8 ppm O(3) up-regulated lung mRNA of CXCL1,2,3 (mouse growth-related oncogene alpha and macrophage-inflammatory protein-2), CXCL10 (IFN-gamma-inducible protein 10), CCL3 (macrophage-inflammatory protein-1alpha), CCL7 (monocyte chemoattractant protein-3), and CCL11 (eotaxin) at 0 h postexposure, and expression of CXCL10, CCL3, and CCL7 mRNA was sustained 18 h postexposure. O(3) increased lung protein levels of CXCL10, CCL7, and CCR3 (CCL7R). The airway epithelium was identified as a source of CCL7. The role of up-regulated chemokines was determined by administering control IgG or IgG Abs against six murine chemokines before O(3) exposure. As expected, anti-mouse growth-related oncogene-alpha inhibited neutrophil recruitment. Surprisingly, Abs to CCL7 and CXCL10 also decreased neutrophil recruitment by 63 and 72%, respectively. These findings indicate that CCL7 and CXCL10, two chemokines not previously reported to orchestrate neutrophilic inflammation, play a critical role in mediating oxidative stress-induced neutrophilic airway inflammation. These observations may have relevance in induction of neutrophilia in severe asthma. PMID- 11777982 TI - Activation of the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase by macrophage-stimulating protein results in the induction of arginase activity in murine peritoneal macrophages. AB - Regulation of macrophage activities in response to inflammatory stimuli must be finely tuned to promote an effective immune response while, at the same time, preventing damage to the host. Our lab and others have previously shown that macrophage-stimulating protein (MSP), through activation of its receptor RON, negatively regulates NO production in response to IFN-gamma and LPS by inhibiting the expression of inducible NO synthase (iNOS). Furthermore, activated macrophages from mice harboring targeted mutations in RON produce increased levels of NO both in vitro and in vivo, rendering them more susceptible to LPS induced endotoxic shock. In this study, we demonstrate that stimulation of murine peritoneal macrophages with MSP results in the RON-dependent up-regulation of arginase, an enzyme associated with alternative activation that competes with iNOS for the substrate L-arginine, the products of which are involved in cell proliferation and matrix synthesis. Expression of other genes associated with alternative activation, including scavenger receptor A and IL-1R antagonist, is also up-regulated in MSP-stimulated murine macrophages. Stimulation of cells with IFN-gamma and LPS blocks the ability of MSP to induce arginase activity. However, pretreatment of cells with MSP results in the up-regulation of arginase and inhibits their ability to produce NO in response to IFN-gamma and LPS, even in the presence of excess substrate, suggesting that the inhibition of NO by MSP occurs primarily through its ability to regulate iNOS expression. PMID- 11777983 TI - IL-6 secretion by human pancreatic periacinar myofibroblasts in response to inflammatory mediators. AB - There is increasing evidence that IL-6 plays an important role in the pathophysiology of acute pancreatitis via its broad proinflammatory actions. To identify the local biosynthetic site for IL-6 in human pancreas, we investigated IL-6 secretion in human pancreatic periacinar myofibroblasts. IL-6 secretion was determined by ELISA and Northern blotting. The activation of NF-kappaB was assessed by EMSA. The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6 secretion was rapidly induced by IL-17, IL 1beta, and TNF-alpha. EMSAs demonstrated that IL-17, IL-1beta, and TNF-alpha induced NF-kappaB activation within 1.5 h after stimulation, and a blockade of NF kappaB activation by the pyrrolidine derivative of dithiocarbamate and tosyl-phe chloromethylketone markedly reduced the IL-17-, IL-1beta-, or TNF-alpha-induced IL-6 gene expression. Furthermore, IL-17, IL-1beta, and TNF-alpha induced a rapid activation of extracellular signal-related kinase p42/44 and p38 MAPKs, and specific MAPK inhibitors (SB203580, PD98059, and U0216) significantly reduced IL 17-, IL-1beta-, or TNF-alpha-induced IL-6 secretion, indicating the role of MAPKs in the induction of IL-6. The combination of either IL-17 plus IL-1beta or IL-17 plus TNF-alpha enhanced IL-6 secretion and IL-6 mRNA expression; in particular, the effects of IL-17 plus TNF-alpha were much stronger than those induced by IL 17 plus IL-1beta. TNF-alpha-induced IL-6 mRNA degraded rapidly at any concentrations, and the combination of IL-17 and TNF-alpha markedly enhanced IL-6 mRNA stability. This indicates that the effects of IL-17 plus TNF-alpha were regulated at the post-transcriptional level. In conclusion, pancreatic periacinar myofibroblasts secreted a large amount of IL-6 in response to proinflammatory cytokines. These cells might play an important role in the pathogenesis of acute pancreatitis via IL-6 secretion. PMID- 11777984 TI - 129X1/SvJ mouse strain has a novel defect in inflammatory cell recruitment. AB - Vitamin D-binding protein (DBP) has been reported to contribute to innate immunity. To verify prior in vitro and cell-based observations supporting this role, we assessed the ability of a recently developed DBP-null mouse line to recruit neutrophils and macrophages to a site of chemical inflammation. The interrupted DBP allele had been generated by homologous recombination in 129X1/SvJ embryonic stem cells and these cells were subsequently used to generate a line of DBP(-/-) (null) mice. Initial studies revealed a marked defect in the ability of these DBP(-/-) mice to recruit cells to the peritoneum after localized thioglycolate injection. However, progressive outcrossing of the DBP(-/-) mice to the C57BL/6J strain, conducted to provide a uniform genetic background for comparison of DBP-null and control mice, resulted in a progressive increase in cell recruitment by the DBP(-/-) mice and a loss in their apparent recruitment defect when compared with the DPB wild-type controls. These data suggested that the observed recruitment phenotype initially attributed to the absence of DBP was not linked to the DBP locus, but instead reflected the underlying genetic composition of the 129X1/SvJ ES cells used for the initial DBP gene disruption. A profound cell recruitment defect was confirmed in the 129X1/SvJ mice by direct analysis. Each of three commonly used inbred lines was discovered to have a distinct level of cell recruitment to a uniform stimulus (C57BL/6J > BALB/c > CD1 > 129X1/SvJ). Thus, this study failed to support a unique role for DBP in cellular recruitment during a model inflammatory response. Instead, the data revealed a novel and profound defect of cell recruitment in 129X1/SvJ mice, the strain most commonly used for gene deletion studies. PMID- 11777985 TI - Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. AB - Leptin is produced almost exclusively by adipocytes and regulates body weight at the hypothalamic level. In addition, recent studies showed that leptin plays an important role in T lymphocyte responses. To examine the role of leptin in Ag induced arthritis, the development of joint inflammation was assessed in immunized leptin-deficient mice (ob/ob), +/?, and wild-type mice (+/+) following the administration of methylated BSA into the knees. The results showed that ob/ob mice developed less severe arthritis compared with control mice. The levels of IL-1beta and TNF-alpha mRNA in the synovium of arthritic knees were lower in ob/ob than in +/? mice. In vitro Ag-specific T cell proliferative responses were significantly decreased in ob/ob mice with lower IFN-gamma and higher IL-10 production, suggesting a shift toward a Th2-type response in ob/ob mice. The serum levels of anti-methylated BSA Abs of any isotype were significantly decreased in arthritic ob/ob mice compared with controls. Essentially identical results were obtained in db/db mice, which lack the expression of the long isoform of leptin receptor. By RT-PCR, we observed that B lymphocytes express leptin receptor mRNA, indicating that in addition to its effect on the cellular response, leptin may exert a direct effect on B cell function. In conclusion, leptin contributes to the mechanisms of joint inflammation in Ag-induced arthritis by regulating both humoral and cell-mediated immune responses. PMID- 11777986 TI - Selective intracellular delivery of dexamethasone into activated endothelial cells using an E-selectin-directed immunoconjugate. AB - In chronic inflammatory diseases, the endothelium is an attractive target for pharmacological intervention because it plays an important role in leukocyte recruitment. Hence, inhibition of endothelial cell activation and consequent leukocyte infiltration may improve therapeutic outcome in these diseases. We report on a drug targeting strategy for the selective delivery of the anti inflammatory drug dexamethasone to activated endothelial cells, using an E selectin-directed drug-Ab conjugate. Dexamethasone was covalently attached to an anti-E-selectin Ab, resulting in the so-called dexamethasone-anti-E-selectin conjugate. Binding of the conjugate to E-selectin was studied using surface plasmon resonance and immunohistochemistry. Furthermore, internalization of the conjugate was studied using confocal laser scanning microscopy and immuno transmission electron microscopy. It was demonstrated that the dexamethasone-anti E-selectin conjugate, like the unmodified anti-E-selectin Ab, selectively bound to TNF-alpha-stimulated endothelial cells and not to resting endothelial cells. After binding, the conjugate was internalized and routed to multivesicular bodies, which is a lysosome-related cellular compartment. After intracellular degradation, pharmacologically active dexamethasone was released, as shown in endothelial cells that were transfected with a glucocorticoid-responsive reporter gene. Furthermore, intracellularly delivered dexamethasone was able to down regulate the proinflammatory gene IL-8. In conclusion, this study demonstrates the possibility to selectively deliver the anti-inflammatory drug dexamethasone into activated endothelial cells, using an anti-E-selectin Ab as a carrier molecule. PMID- 11777987 TI - Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene. AB - To investigate the role of HLA-DQ molecules and/or CD4(+) T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Abeta(null)) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4(null) mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4(null) mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4(null) mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4(null) mice compared with the high response in DQ/CD4(+) counterparts and was only partially augmented by CD4(+) T cell transfer. The DQ6/CD4(null) mice showed Th1/Th2-type cytokines and SRW specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4(+) mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4(null) mice was mediated by HLA-DQ-restricted CD4(-)CD8(-)NK1.1(-) T cells. FACS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4(-)CD8(-)TCRalphabeta(+) T cells in SRW treated DQ6/CD4(null) mice. These cells produced IL-4, IL-5, IL-13, and IFN-gamma when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4(null) mice. Our study shows a role for HLA-DQ-restricted CD4(+) and DN T cells in the allergic response. PMID- 11777988 TI - The interrelated roles of TGF-beta and IL-10 in the regulation of experimental colitis. AB - In the present study, we define the relation between TGF-beta and IL-10 in the regulation of the Th1-mediated inflammation occurring in trinitrobenzene sulfonic acid (TNBS)-colitis. In initial studies, we showed that the feeding of trinitrophenol-haptenated colonic protein to SJL/J mice induces CD4(+) regulatory T cells that transfer protection from induction of TNBS-colitis, and that such protection correlates with cells producing TGF-beta, not IL-10. Further studies in which SJL/J mice were fed haptenated colonic protein, and then administered either anti-TGF-beta or anti-IL-10 at the time of subsequent TNBS administration per rectum, showed that while both Abs abolished protection, anti-TGF-beta administration prevented TGF-beta secretion, but left IL-10 secretion intact; whereas anti-IL-10 administration prevented both TGF-beta secretion and IL-10 secretion. Thus, it appeared that the protective effect of IL-10 was an indirect consequence of its effect on TGF-beta secretion. To establish this point further, we conducted adoptive transfer studies and showed that anti-IL-10 administration had no effect on induction of TGF-beta producing T cells in donor mice. However, it did inhibit their subsequent expansion in recipient mice, probably by regulating the magnitude of the Th1 T cell response which would otherwise inhibit the TGF-beta response. Therefore, these studies suggest that TGF-beta production is a primary mechanism of counter-regulation of Th1 T cell-mediated mucosal inflammation, and that IL-10 is necessary as a secondary factor that facilitates TGF-beta production. PMID- 11777989 TI - Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. AB - Adoptive immunotherapy with EBV-specific CTL (EBV-CTL) effectively prevents and treats EBV-driven lymphoproliferation in immunocompromised hosts. EBV seronegative solid organ transplant recipients are at high risk of EBV-driven lymphoproliferation because they lack EBV-specific memory T cells. For the same reason, standard techniques for generating EBV-CTL in vitro from EBV-naive individuals are unsuccessful. To overcome this problem, we compared several methods of expanding EBV-CTL from seronegative adults and children. First, the standard protocol, using EBV-transformed lymphoblastoid B cell lines (LCL) as the source of APC, was compared with protocols using EBV-Ag-loaded dendritic cells as APC. Surprisingly, the standard protocol effectively generated CTL from all seronegative adults. The additional finding of EBV-DNA in the peripheral blood of three of these four adults suggested that some individuals may develop cellular, but not humoral, immune responses to EBV. By contrast, LCL failed to reactivate EBV-CTL from any of the six EBV-seronegative children. EBV-Ag-loaded dendritic cells could expand EBV-CTL, but only in a minority of children. However, the selective expansion of CD25-expressing T cells, 9-11 days after activation with LCL alone, proved to be a simple and reliable method for generating EBV-CTL from all seronegative children. The majority of these CTL were CD4(+) (71 +/- 26%) and demonstrated HLA class II-restricted, EBV-specific killing. Our results suggest that a negative EBV serology does not accurately identify EBV-negative individuals. In addition, our method for selecting EBV-specific CTL from naive individuals by precursor cell enrichment may be applicable to the immunotherapy of cancer patients with a low frequency of tumor- or virus-specific CTL. PMID- 11777990 TI - Influence of Mycobacterium bovis bacillus Calmette-Guerin on antibody and cytokine responses to human neonatal vaccination. AB - The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells. PMID- 11777991 TI - Monophosphoryl lipid A activates both human dendritic cells and T cells. AB - The induction of dendritic cell (DC) maturation is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. In this study, we have investigated the effects of monophosphoryl lipid A (MPL) on human monocyte-derived DC as well as peripheral blood T cells. Calcium mobilization, mitogen-activated protein kinase activation, and the NF-kappaB transcription factor were induced after MPL stimulation of DC and required high doses of MPL (100 microg/ml). Maturation parameters such as production of IL-12 and increases in cell surface expression of HLA-DR, CD80, CD86, CD40, and CD83 were observed following DC treatment with MPL. However, lower levels of IL-12 were induced by MPL when compared with lipopolysaccharide. This is likely to be related to differences in the kinetics of extracellular signal-related kinase 1/2 and p-38 phosphorylation induced by both molecules. Although maturation induced by MPL was weaker when compared with lipopolysaccharide, it appeared to be sufficient to support optimal activation of allogeneic naive CD45RA(+) T cell and anti-tetanus toxoid CD4 T cells. MPL at low doses (5 microg/ml) had no impact on DC maturation, while its addition to DC-T cell cocultures induced full T cell activation. The observed effect was related to the fact that MPL also acts directly on T cells, likely through their Toll like receptors, by increasing their intracellular calcium and up-regulating their CD40 ligand expression. Together, these data support a model where MPL enhances T cell responses by having an impact on DC and T cells. PMID- 11777993 TI - Igs from patients with Graves' disease induce the expression of T cell chemoattractants in their fibroblasts. AB - Thyroid-associated ophthalmopathy and dermopathy are connective tissue manifestations of Graves' disease (GD). Tissue remodeling is a prominent feature of both and is apparently driven by recruited T cells. In this study, we report that IgG isolated from patients with GD (GD-IgG) up-regulates T lymphocyte chemoattractant activity in GD-derived fibroblasts from orbit, thyroid, and several regions of skin. This chemoattractant activity, absent in fibroblasts from donors without known thyroid disease, is partially susceptible to neutralization by anti-IL-16 and anti-RANTES Abs. IL-16 is a CD4(+)-specific chemoattractant and RANTES is a C-C-type chemokine. IL-16 and RANTES protein levels, as determined by specific ELISAs, are substantially increased by GD-IgG in GD fibroblasts. Addition of the macrolide, rapamycin, to fibroblast culture medium blocked the up-regulation by GD-IgG of IL-16, implicating the FRAP/mTOR/p70(s6k) pathway in the induction of IL-16 expression. These findings suggest a specific mechanism for activation of fibroblasts in GD resulting in the recruitment of T cells. They may provide insight into a missing link between the glandular and extrathyroidal manifestations of GD. PMID- 11777992 TI - Nonmitogenic CD3 antibody reverses virally induced (rat insulin promoter lymphocytic choriomeningitis virus) autoimmune diabetes without impeding viral clearance. AB - Treatment with nonmitogenic CD3 Ab reverses established autoimmune diabetes in nonobese diabetic mice by restoring self-tolerance, and is currently under clinical evaluation in patients presenting recent onset type I diabetes. Due to the immunosuppressive potential of this strategy, it was relevant to explore how this treatment would influence the outcome of concomitant viral infections. In this study, we used a transgenic model of virally induced autoimmune diabetes (rat insulin promoter-lymphocytic choriomeningitis virus) that allows for more precise tracking of the autoaggressive response and choice of the time point for initiation of autoimmunity. CD3 was most effective during a clearly defined prediabetic phase and prevented up to 100% of diabetes by drastically lowering activation of autoaggressive CD8 lymphocytes and their production of inflammatory cytokines. Interestingly, reversion of established disease could be achieved as well, when nonmitogenic CD3 was administered late during pathogenesis to overtly diabetic recipients. Most importantly, competence to clear viral infections was maintained. Thus, administration of nonmitogenic CD3 prevents diabetes by sufficient systemic reduction of (auto)aggressive lymphocytes, but without compromising antiviral immune competence. PMID- 11777995 TI - Images in clinical medicine. Syringomyelia. PMID- 11777994 TI - Pre-existing immunity to tyrosinase-related protein (TRP)-2, a new TRP-2 isoform, and the NY-ESO-1 melanoma antigen in a patient with a dramatic response to immunotherapy. AB - We have performed a detailed analysis of the recognition of melanoma Ags by the tumor-infiltrating lymphocytes (TIL) 1790, isolated from a patient who experienced a dramatic tumor regression following immunization with peptides from the gp100, MART-1, and tyrosinase Ags. This TIL was found to recognize HLA-A2 restricted CTL epitopes in tyrosinase-related protein (TRP)-2 (clone MR7) and NY ESO-1 (clone M8). These epitopes were the same as the previously identified nonapeptide TRP-2: 180-188, and the overlapping NY-ESO-1 peptides, obtained by using lymphocytes from in vitro stimulation. We also cloned a previously unknown TRP-2 mRNA isoform (TRP-2-6b) that contained two novel exons alternatively spliced from the sixth intron between exons 6 and 7 of TRP-2 mRNA. The isoform encoded an HLA-A2-restricted antigenic epitope recognized by TIL clone MB4. An immunologic analysis of the patient's PBMC obtained before treatment showed the presence of high reactivity against NY-ESO-1 and both TRP-2 Ags, but not the Ags used for immunization. Because immune response against these Ags was less pronounced, it is possible that NY-ESO-1, TRP-2, and TRP-2-6b may be of importance in the generation of CTL-mediated tumor destruction and may have played a role in the dramatic tumor regression seen in this patient. PMID- 11777996 TI - Can the heart repair itself? PMID- 11777997 TI - Chimerism of the transplanted heart. AB - BACKGROUND: Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart. The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor. METHODS: We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients. Primitive cells bearing Y chromosomes that expressed c-kit, MDR1, and Sca-1 were also investigated. RESULTS: Myocytes, coronary arterioles, and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative. As compared with the ventricles of control hearts, the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit, MDR1, or Sca-1. The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts, and 12 to 16 percent of these cells contained a Y chromosome. Undifferentiated cells were negative for markers of bone marrow origin. Progenitor cells expressing MEF2, GATA-4, and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified. CONCLUSIONS: Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart. Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts. PMID- 11777998 TI - A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. AB - BACKGROUND: Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder. METHODS: In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year. RESULTS: Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group. CONCLUSIONS: Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol. PMID- 11777999 TI - Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. AB - BACKGROUND: The hemolytic-uremic syndrome is a thrombotic complication of Escherichia coli O157:H7 infection. It is not known whether the coagulation abnormalities precede, and potentially cause, this disorder. METHODS: In 53 children infected with E. coli O157:H7, we measured a panel of markers indicating activation of the clotting cascade and renal function within four days after the onset of illness. These markers were measured again in as many as possible of the 16 children in whom the hemolytic-uremic syndrome developed. RESULTS: The children in whom the hemolytic-uremic syndrome subsequently developed had significantly higher median plasma concentrations of prothrombin fragment 1+2, tissue plasminogen activator (t-PA) antigen, t-PA-plasminogen-activator inhibitor type 1 (PAI-1) complex, and D-dimer than children with uncomplicated infection. These abnormalities preceded the development of azotemia and thrombocytopenia. When the hemolytic-uremic syndrome developed, the urinary concentrations of beta2 microglobulin and N-acetyl-beta-glucosaminidase rose significantly (P=0.03 for both increases); the plasma concentrations of t-PA antigen, t-PA-PAI-1 complex, D dimer, and plasmin-antiplasmin complex also increased significantly. The concentration of t-PA antigen correlated with that of the t-PA-PAI-1 complex in a linear regression model (squared correlation coefficient, 0.80; P<0.001). CONCLUSIONS: In the hemolytic-uremic syndrome, thrombin generation (probably due to accelerated thrombogenesis) and inhibition of fibrinolysis precede renal injury and may be the cause of such injury. PMID- 11778000 TI - The interval between pregnancies and the risk of preeclampsia. AB - BACKGROUND: The risk of preeclampsia is generally lower in second pregnancies than in first pregnancies, but not if the mother has a new partner for the second pregnancy. One explanation is that the risk is reduced with repeated maternal exposure and adaptation to specific antigens from the same partner. However, the difference in risk might instead be explained by the interval between births. A longer interbirth interval may be associated with both a change of partner and a higher risk of preeclampsia. METHODS: We used data from the Medical Birth Registry of Norway, a population-based registry that includes births that occurred between 1967 and 1998. We studied 551,478 women who had two or more singleton deliveries and 209,423 women who had three or more singleton deliveries. RESULTS: Preeclampsia occurred during 3.9 percent of first pregnancies, 1.7 percent of second pregnancies, and 1.8 percent of third pregnancies when the woman had the same partner. The risk in a second or third pregnancy was directly related to the time that had elapsed since the preceding delivery, and when the interbirth interval was 10 years or more, the risk approximated that among nulliparous women. After adjustment for the presence or absence of a change of partner, maternal age, and year of delivery, the odds ratio for preeclampsia for each one-year increase in the interbirth interval was 1.12 (95 percent confidence interval, 1.11 to 1.13). In unadjusted analyses, a pregnancy involving a new partner was associated with higher risk of preeclampsia, but after adjustment for the interbirth interval, the risk of preeclampsia was reduced (odds ratio for preeclampsia with a change of partner, 0.73; 95 percent confidence interval, 0.66 to 0.81). CONCLUSIONS: The protective effect of previous pregnancy against preeclampsia is transient. After adjustment for the interval between births, a change of partner is not associated with an increased risk of preeclampsia. PMID- 11778001 TI - Images in clinical medicine. Spontaneous resolution of a pubic-symphysis diastasis. PMID- 11778002 TI - Clinical practice. Screening for colorectal cancer. PMID- 11778003 TI - Alpha1-antitrypsin deficiency--a model for conformational diseases. PMID- 11778004 TI - Regeneration of the human heart--no chimera? PMID- 11778005 TI - Prevention of relapse in schizophrenia. PMID- 11778006 TI - The hemolytic-uremic syndrome--toxin, thrombin, and thrombosis. PMID- 11778007 TI - Postmenopausal hormone-replacement therapy. PMID- 11778008 TI - Helicobacter pylori infection and the development of gastric cancer. PMID- 11778009 TI - Subclinical hyperthyroidism. PMID- 11778010 TI - Reversible metronidazole-induced lesions of the cerebellar dentate nuclei. PMID- 11778011 TI - Mapping the one-dimensional electronic States of nanotube peapod structures. AB - Arrays of C60 molecules nested inside single-walled nanotubes represent a class of nanoscale materials having tunable properties. We report electronic measurements of this system made with a scanning tunneling microscope and demonstrate that the encapsulated C60 molecules modify the local electronic structure of the nanotube. Our measurements and calculations also show that a periodic array of C60 molecules gives rise to a hybrid electronic band, which derives its character from both the nanotube states and the C60 molecular orbitals. PMID- 11778013 TI - The isomap algorithm and topological stability. PMID- 11778012 TI - Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. AB - The presence of galactose alpha-1,3-galactose residues on the surface of pig cells is a major obstacle to successful xenotransplantation. Here, we report the production of four live pigs in which one allele of the alpha-1,3 galactosyltransferase locus has been knocked out. These pigs were produced by nuclear transfer technology; clonal fetal fibroblast cell lines were used as nuclear donors for embryos reconstructed with enucleated pig oocytes. PMID- 11778014 TI - Another year for Science. PMID- 11778015 TI - U.S. budget. Biomedicine gets record raise as Congress sets 2002 spending. PMID- 11778016 TI - Xenotransplantation. Cloned pigs may help overcome rejection. PMID- 11778017 TI - Antibiotic resistance. Livestock feed ban preserves drugs' power. PMID- 11778018 TI - Aging research. Cancer-stalling system accelerates aging. PMID- 11778019 TI - Climate change. Reducing uncertainties of global warming. PMID- 11778020 TI - Nuclear science. U.S. breeder reactor runs out of lives. PMID- 11778021 TI - Harvard disappearance. Missing biologist found dead in river. PMID- 11778022 TI - Solar system exploration. Planetary science's defining moment. PMID- 11778023 TI - Solar system exploration. Lab rivalry spices up solar system exploration. PMID- 11778024 TI - Solar system exploration. Researchers fear merger could muffle their voice. PMID- 11778025 TI - Solar system exploration. Tight budget makes for an uncertain future. PMID- 11778026 TI - Solar system exploration. Technology is essential, but it's a tough sell. PMID- 11778028 TI - Cosmology. How the cosmic dark age ended. PMID- 11778027 TI - Portraits of science. Mosquitoes bite more than once. AB - Ronald Ross discovered that the plasmodium parasite--'Laveran's germ'--was transmitted by anopheline mosquitoes to human beings to cause malaria. This discovery won him a Nobel Prize in 1902, but the route to this success was by no means clear. He was an indifferent student, he liked to write novels and poems and only just managed to gain a medical qualification. Fortuitously he was mediocre enough to enter the least prestigious section of the Indian Medical Service, which put him directly in contact with the parasites that were to become his passion. Despite honours being showered on him, life after the Prize also was not straightforward, he was irrascible and his innovative mathematical and economic approaches to disease control were overlooked. PMID- 11778029 TI - Development. Carbohydrate recognition in spermatogenesis. PMID- 11778031 TI - Geophysics. Caught offside. PMID- 11778032 TI - Surface science. Water on a metal surface. PMID- 11778030 TI - Aging. Dietary advice on Q. PMID- 11778033 TI - Plant biology. Prime time for cellulose. PMID- 11778035 TI - The runts of the cosmic litter. PMID- 11778034 TI - Great balls of fire. Star formation: a Web supplement. PMID- 11778036 TI - The quest for population III. PMID- 11778037 TI - Clustered star formation and the origin of stellar masses. AB - Star clusters are ubiquitous in galaxies of all types and at all stages of their evolution. We also observe them to be forming in a wide variety of environments, ranging from nearby giant molecular clouds to the supergiant molecular clouds found in starburst and merging galaxies. The typical star in our galaxy and probably in others formed as a member of a star cluster, so star formation is an intrinsically clustered and not an isolated phenomenon. The greatest challenge regarding clustered star formation is to understand why stars have a mass spectrum that appears to be universal. This review examines the observations and models that have been proposed to explain these fundamental issues in stellar formation. PMID- 11778038 TI - Isolated star formation: from cloud formation to core collapse. AB - The formation of stars is one of the most fundamental problems in astrophysics, as it underlies many other questions, on scales from the formation of galaxies to the formation of the solar system. The physical processes involve the turbulent behavior of a partially ionized medium containing a non-uniform magnetic field. Current debate centers around the time taken for turbulence to decay and the relative importance of the roles played by magnetic fields and turbulence. Technological advances such as millimeter-wave cameras have made possible observations of the temperature and density profiles, and statistical calculations of the lifetimes, of objects collapsing under their own self-gravity and those on the verge of collapse. Increased computing power allows more complex models to be made that include magnetic and turbulent effects. No current model can reproduce all of the observations. PMID- 11778039 TI - The initial mass function of stars: evidence for uniformity in variable systems. AB - The distribution of stellar masses that form in one star formation event in a given volume of space is called the initial mass function (IMF). The IMF has been estimated from low-mass brown dwarfs to very massive stars. Combining IMF estimates for different populations in which the stars can be observed individually unveils an extraordinary uniformity of the IMF. This general insight appears to hold for populations including present-day star formation in small molecular clouds, rich and dense massive star-clusters forming in giant clouds, through to ancient and metal-poor exotic stellar populations that may be dominated by dark matter. This apparent universality of the IMF is a challenge for star formation theory, because elementary considerations suggest that the IMF ought to systematically vary with star-forming conditions. PMID- 11778041 TI - Partial dissociation of water on Ru(0001). AB - Initial water deposition on the moderately reactive precious metal surface Ru(0001) has been thought to produce an ice-like bilayer. However, calculations from first principles show that the wetting layer observed on Ru(0001) cannot be formed of undissociated water molecules. An energetically favorable alternative, consistent with the remarkable observation that the wetting layer's oxygen atoms are nearly coplanar, is a half-dissociated monolayer wherein water molecules and hydroxyl fragments are hydrogen-bonded in a hexagonal structure and hydrogen atoms bind directly to the metal. PMID- 11778040 TI - Fluorescent signaling in parrots. PMID- 11778042 TI - A one-step conversion of benzene to phenol with a palladium membrane. AB - Existing phenol production processes tend to be energy-consuming and produce unwanted by-products. We report an efficient process using a shell-and-tube reactor, in which a gaseous mixture of benzene and oxygen is fed into a porous alumina tube coated with a palladium thin layer and hydrogen is fed into the shell. Hydrogen dissociated on the palladium layer surface permeates onto the back and reacts with oxygen to give active oxygen species, which attack benzene to produce phenol. This one-step process attained phenol formation selectivities of 80 to 97% at benzene conversions of 2 to 16% below 250 degrees C (phenol yield: 1.5 kilograms per kilogram of catalyst per hour at 150 degrees C). PMID- 11778043 TI - Constraints on melt movement beneath the East Pacific Rise from 230Th-238U disequilibrium. AB - We report 230Th-238U disequilibrium data on mid-ocean ridge basalts recovered 5 to 40 kilometers off the ridge axis near 9 degrees 30'N of the East Pacific Rise. These data indicate near-symmetrical eruptions of normal mid-ocean ridge basalts (NMORBs) and incompatible element-enriched mid-ocean ridge basalts (EMORBs) as far as 20 kilometers off axis. Our results suggest large-scale subsurface lateral transport of NMORB melt at 19 to 21 centimeters per year and also provide constraints on the petrogenesis of EMORBs of off-axis origin. PMID- 11778044 TI - Quantifying uncertainties in climate system properties with the use of recent climate observations. AB - We derive joint probability density distributions for three key uncertain properties of the climate system, using an optimal fingerprinting approach to compare simulations of an intermediate complexity climate model with three distinct diagnostics of recent climate observations. On the basis of the marginal probability distributions, the 5 to 95% confidence intervals are 1.4 to 7.7 kelvin for climate sensitivity and -0.30 to -0.95 watt per square meter for the net aerosol forcing. The oceanic heat uptake is not well constrained, but ocean temperature observations do help to constrain climate sensitivity. The uncertainty in the net aerosol forcing is much smaller than the uncertainty range for the indirect aerosol forcing alone given in the Intergovernmental Panel on Climate Change Third Assessment Report. PMID- 11778045 TI - Intracellular iron minerals in a dissimilatory iron-reducing bacterium. AB - Among prokaryotes, there are few examples of controlled mineral formation; the formation of crystalline iron oxides and sulfides [magnetite (Fe3O4) or greigite (Fe3S4)] by magnetotactic bacteria is an exception. Shewanella putrefaciens CN32, a Gram-negative, facultative anaerobic bacterium that is capable of dissimilatory iron reduction, produced microscopic intracellular grains of iron oxide minerals during growth on two-line ferrihydrite in a hydrogen-argon atmosphere. The minerals, formed at iron concentrations found in the soil and sedimentary environments where these bacteria are active, could represent an unexplored pathway for the cycling of iron by bacteria. PMID- 11778046 TI - Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. AB - The isoprenylated benzoquinone coenzyme Q is a redox-active lipid essential for electron transport in aerobic respiration. Here, we show that withdrawal of coenzyme Q (Q) from the diet of wild-type nematodes extends adult life-span by approximately 60%. The longevity of clk-1, daf-2, daf-12, and daf-16 mutants is also extended by a Q-less diet. These results establish the importance of Q in life-span determination. The findings suggest that Q and the daf-2 pathway intersect at the mitochondria and imply that a concerted production coupled with enhanced scavenging of reactive oxygen species contributes to the substantial life-span extension. PMID- 11778047 TI - Germ cell survival through carbohydrate-mediated interaction with Sertoli cells. AB - Spermatogenesis is a precisely regulated process in which the germ cells closely interact with Sertoli cells. The molecular basis of this cell-cell adhesion is unknown. Here, we demonstrate that targeted disruption of Man2a2, a gene encoding alpha-mannosidase IIx (MX), an enzyme that forms intermediate asparagine-linked carbohydrates (N-glycans), results in Man2a2 null males that are largely infertile. The Man2a2 null spermatogenic cells fail to adhere to Sertoli cells and are prematurely released from the testis to epididymis. We identified an N glycan structure that plays a key role in germ cell-Sertoli cell adhesion and showed that a specific carbohydrate was required for spermatogenesis. PMID- 11778048 TI - Combined functional genomic maps of the C. elegans DNA damage response. AB - Many human cancers originate from defects in the DNA damage response (DDR). Although much is known about this process, it is likely that additional DDR genes remain to be discovered. To identify such genes, we used a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis in Caenorhabditis elegans. Together, these approaches identified 12 worm DDR orthologs and 11 novel DDR genes. One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia. Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases. PMID- 11778049 TI - Construction and analysis of a human-chimpanzee comparative clone map. AB - The recently released human genome sequences provide us with reference data to conduct comparative genomic research on primates, which will be important to understand what genetic information makes us human. Here we present a first generation human-chimpanzee comparative genome map and its initial analysis. The map was constructed through paired alignment of 77,461 chimpanzee bacterial artificial chromosome end sequences with publicly available human genome sequences. We detected candidate positions, including two clusters on human chromosome 21 that suggest large, nonrandom regions of difference between the two genomes. PMID- 11778050 TI - Nucleotide variation along the Drosophila melanogaster fourth chromosome. AB - The Drosophila melanogaster fourth chromosome, believed to be nonrecombining and invariable, is a classic example of the effect of natural selection in eliminating genetic variation in linked loci. However, in a chromosome-wide assay of nucleotide variation in natural populations, we have observed a high level of polymorphism in a approximately 200-kilobase region and marked levels of polymorphism in several other fragments interspersed with regions of little variation, suggesting different evolutionary histories in different chromosomal domains. Statistical tests of neutral evolution showed that a few haplotypes predominate in the 200-kilobase polymorphic region. Finally, contrary to the expectation of no recombination, we identified six recombination events within the chromosome. Thus, positive Darwinian selection and recombination have affected the evolution of this chromosome. PMID- 11778051 TI - Role of cell-specific SpoIIIE assembly in polarity of DNA transfer. AB - SpoIIIE mediates postseptational chromosome partitioning in Bacillus subtilis, but the mechanism controlling the direction of DNA transfer remains obscure. Here, we demonstrated that SpoIIIE acts as a DNA exporter: When SpoIIIE was synthesized in the larger of the two cells necessary for sporulation, the mother cell, DNA was translocated into the smaller forespore; however, when it was synthesized in the forespore, DNA was translocated into the mother cell. Furthermore, the DNA-tracking domain of SpoIIIE inhibited SpoIIIE complex assembly in the forespore. Thus, during sporulation, chromosome partitioning is controlled by the preferential assembly of SpoIIIE in one daughter cell. PMID- 11778052 TI - Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. AB - Tumstatin is a 28-kilodalton fragment of type IV collagen that displays both anti angiogenic and proapoptotic activity. Here we show that tumstatin functions as an endothelial cell-specific inhibitor of protein synthesis. Through a requisite interaction with alphaVbeta3 integrin, tumstatin inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3-kinase), protein kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR), and it prevents the dissociation of eukaryotic initiation factor 4E protein (eIF4E) from 4E-binding protein 1. These results establish a role for integrins in mediating cell specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells. PMID- 11778053 TI - Mediation of hippocampal mossy fiber long-term potentiation by presynaptic Ih channels. AB - Hippocampal mossy fiber long-term potentiation (LTP) is expressed presynaptically, but the exact mechanisms remain unknown. Here, we demonstrate the involvement of the hyperpolarization-activated cation channel (Ih) in the expression of mossy fiber LTP. Established LTP was blocked and reversed by Ih channel antagonists. Whole-cell recording from granule cells revealed that repetitive stimulation causes a calcium- and Ih-dependent long-lasting depolarization mediated by protein kinase A. Depolarization at the terminals would be expected to enhance transmitter release, whereas somatic depolarization would enhance the responsiveness of granule cells to afferent input. Thus, Ih channels play an important role in the long-lasting control of transmitter release and neuronal excitability. PMID- 11778055 TI - The rise and fall of preoperative autologous blood donation. PMID- 11778054 TI - Sitosterol-beta-glucoside as primer for cellulose synthesis in plants. AB - Cellulose synthesis in plants requires beta-1,4-glucan chain initiation, elongation, and termination. The process of chain elongation is likely to be distinct from the process of chain initiation. We demonstrate that a CesA glucosyltransferase initiates glucan polymerization by using sitosterol-beta glucoside (SG) as primer. Cotton fiber membranes synthesize sitosterol cellodextrins (SCDs) from SG and uridine 5'-diphosphate-glucose (UDP-Glc) under conditions that also favor cellulose synthesis. The cellulase encoded by the Korrigan (Kor) gene, required for cellulose synthesis in plants, may function to cleave SG from the growing polymer chain. PMID- 11778056 TI - Transfusion medicine illustrated. Erythrophagocytosis after an ABO-mismatched stem cell transplant. PMID- 11778057 TI - Cataracts in neutrophil donors stimulated with adrenal corticosteroids. AB - BACKGROUND: A relatively young man (43 years old) was found to have a cataract after receiving prednisone before each of 35 neutrophil (PMN) donations over several years. Because corticosteroids are known to induce posterior subcapsular cataracts (PSCs), additional repeat PMN donors were examined ophthalmologically. STUDY DESIGN AND METHODS: A controlled, blinded study was performed in 11 PMN donors who received prednisone with or without G-CSF before 17 to 46 leukapheresis donations over an average of 8.5 years. Control subjects were nine plateletpheresis donors of comparable age and donation experience, but they had never donated PMNs. A complete eye examination was performed by an ophthalmologist who was unaware of the donor's status (PMN vs. platelet). RESULTS: Mild PSCs were found in 36 percent (4/11) of PMN donors versus 0 of 9 platelet donors (p = 0.068). Five of the 22 PMN donor eyes involved versus 0 of the 18 platelet donor eyes involved exhibited PSCs (p = 0.040). Cortical and nuclear cataracts were found similarly in both groups of donors (82% PMN vs. 56% platelet donors; p = 0.217); this indicated that lifestyle factors, independent of corticosteroids, that might predispose to cataract formation probably were comparable. CONCLUSION: Corticosteroids given before PMN donations by leukapheresis might increase the risk of PSCs. Because of widespread renewed interest in PMN transfusions, this potential risk factor--if confirmed by studies of additional PMN donors--is of great international importance. Other centers are urged to perform ophthalmologic examinations on repeat PMN donors to clarify this issue. PMID- 11778058 TI - Computer-assisted audiovisual health history self-interviewing. Results of the pilot study of the Hoxworth Quality Donor System. AB - BACKGROUND: The safety of blood for transfusion depends, in part, on the reliability of the health history given by volunteer blood donors. To improve reliability, a pilot study evaluated the use of an interactive computer-based audiovisual donor interviewing system at a typical midwestern blood center in the United States. STUDY DESIGN AND METHODS: An interactive video screening system was tested in a community donor center environment on 395 volunteer blood donors. Of the donors using the system, 277 completed surveys regarding their acceptance of and opinions about the system. RESULTS: The study showed that an interactive computer-based audiovisual donor screening system was an effective means of conducting the donor health history. The majority of donors found the system understandable and favored the system over a face-to-face interview. Further, most donors indicated that they would be more likely to return if they were to be screened by such a system. CONCLUSION: Interactive computer-based audiovisual blood donor screening is useful and well accepted by donors; it may prevent a majority of errors and accidents that are reportable to the FDA; and it may contribute to increased safety and availability of the blood supply. PMID- 11778059 TI - A study of 178 consecutive vasovagal syncopal reactions from the perspective of safety. AB - BACKGROUND: While vasovagal syncopal reactions have been studied in the past, there are several safety questions that could be further addressed. The purpose of this study was to address these safety questions. STUDY DESIGN AND METHODS: One hundred seventy-eight vasovagal reactions were reported in 1999 from 194,000 blood donations. The reactions were retrospectively reviewed for 38 variables that included donor demographics, symptoms, injury, and final disposition. RESULTS: Sixty-one percent of the syncopal reactions occurred at the refreshment table and 12 percent offsite. Fourteen percent of the donors sustained an injury, usually to the head (10%). Eleven donors (6%) had additional medical care in an emergency room: 4 for injuries, 3 for delayed recovery, and 4 for offsite syncope. None of the donors was admitted to the hospital. One of the injured donors developed postconcussion syndrome and had later sequelae. CONCLUSION: Syncopal reactions most commonly occur at the refreshment table, where preventive safety measures against trauma could be applied. A significant number of syncopal reactions occur offsite, where the environment is less safe. The injuries that occur, particularly to the head, may in rare cases lead to long-term sequelae. PMID- 11778060 TI - Risk behavior in Norwegian blood donors. AB - BACKGROUND: Blood banks ensure the safety of blood components by testing them for a set of known infectious agents and by careful selection of donors based on a self-administered questionnaire and an interview. The purpose of this study is to describe the risk behavior for sexually transmitted diseases in Norwegian blood donors. STUDY DESIGN AND METHODS: A survey of the sexual habits of 5,859 blood donors in the capital of Norway was performed by using anonymous questionnaires. The results were compared with a previous survey of 10,000 randomly selected Norwegian subjects aged 18 to 60 years. The response rates were 70.3 percent and 48.4 percent, respectively. RESULTS: Blood donors had considerably more education than the general population. Their general sexual behavior was similar to that of the rest of the population, although the blood donors had later sexual debut, fewer new partners per year, and a lower frequency of intercourse. In addition, homosexual experience among males was much lower in the donor group. Blood donors were less likely to engage in risk behavior for sexually transmitted diseases than were the general population. Nevertheless, 1.5 percent of the donors reported behavior that would have led to deferral had the behavior been disclosed at the predonation interview. Deferrable donors were more likely to be male and young and to have had many partners. CONCLUSION: Anonymous questionnaires reveal information that is not given at the time of blood donation. PMID- 11778061 TI - Evaluation of a reporting system for bacterial contamination of blood components in the United States. AB - BACKGROUND: The transfusion of blood components contaminated with bacteria may have serious clinical consequences, but few data are available on the incidence of these events. A national effort to assess the frequency of blood component bacterial contamination associated with transfusion reaction (the BaCon Study) was initiated to better estimate their occurrence. STUDY DESIGN AND METHODS: Standard reporting criteria, data collection forms, and a standardized reporting protocol were developed in collaboration with the American Red Cross, AABB, and the Department of Defense. Episodes reported to the BaCon Study were compared with those reported to the FDA's national reporting systems to estimate the extent to which all serious reactions associated with bacterial contamination were captured. RESULTS: During the first 2 years, 38 episodes meeting study criteria were reported; 21 were laboratory-confirmed. The estimated proportion of episodes reported to the BaCon Study (i.e., completeness of coverage) was lower than that reported to the FDA during the same period (0.33 vs. 0.68), but the positive predictive value was higher (0.66 vs.0.28). CONCLUSION: Despite the complexity of obtaining reports from a large number of United States hospitals and transfusion centers, the feasibility and usefulness of the BaCon Study were shown. This study was the only national study in the United States to monitor adverse clinical events associated with bacterial contamination of blood components. By building on hospital-based reporting of transfusion-related adverse events, the BaCon Study serves as a model for the study of other complications associated with blood and blood components. PMID- 11778062 TI - Transfusion-transmitted bacterial infection in the United States, 1998 through 2000. AB - BACKGROUND: Bacterial contamination of blood components can result in transfusion transmitted infection, but the risk is not established. STUDY DESIGN AND METHODS: Suspected cases of transfusion-transmitted bacteremia were reported to the CDC by participating blood collection facilities and transfusion services affiliated with the American Red Cross, AABB, or Department of Defense blood programs from 1998 through 2000. A case was defined as any transfusion reaction meeting clinical criteria in which the same organism species was cultured from a blood component and from recipient blood, with the organism pair confirmed as identical by molecular typing. RESULTS: There were 34 cases and 9 deaths. The rate of transfusion-transmitted bacteremia (in events/million units) was 9.98 for single donor platelets, 10.64 for pooled platelets, and 0.21 for RBC units; for fatal reactions, the rates were 1.94, 2.22, and 0.13, respectively. Patients at greatest risk for death received components containing gram-negative organisms (OR, 7.5; 95% CI, 1.3-64.2; p = 0.009). CONCLUSION: Bacterial contamination of blood is an important cause of transfusion-transmitted infection; infection risk from platelet transfusion is higher compared with that from RBCs, and, overall, the risk of infection from bacterial contamination now may exceed that from viral agents. Recipients of components containing gram-negative organisms are at highest risk for transfusion-related death. The results of this study may help direct efforts to improve transfusion-related patient safety. PMID- 11778063 TI - High-titer screening PCR: a successful strategy for reducing the parvovirus B19 load in plasma pools for fractionation. AB - BACKGROUND: Human parvovirus B19 (B19) is regarded as a potential risk factor for certain patient populations receiving plasma components. STUDY DESIGN AND METHODS: The prevalence of B19 was determined in a limited plasma donor population. Conditions for high-titer screening PCR were designed to allow the removal of plasma donations in the acute phase of infection with virus loads >or=10(7) genome equivalents per milliliter before manufacturing. Antithrombin III lots originating from screened plasma were compared to lots originating from untested plasma with respect to their B19 DNA load by a sensitive PCR assay. RESULTS: B19 was shown to have a prevalence of about 1 per 800 plasma donations. Only a minority (1/8000) of occurrences were in the acute phase of infection. Removing plasma units with high virus load as determined by high-titer screening PCR significantly decreased peak virus loads of plasma pools for fractionation. Together with a virus-removal capacity of 10.4 log(10) of the manufacturing process, this screening resulted in a final antithrombin III product that was nonreactive for B19 on PCR. CONCLUSION: Combining the strategy of high-titer screening PCR with the virus reduction capacity of the manufacturing process considerably increased the margin of B19 virus safety of antithrombin III. This strategy should have positive impact on other plasma components as well. PMID- 11778064 TI - Lack of transmission of TT virus through immunoglobulins. AB - BACKGROUND: A high prevalence of TT virus (TTV) infection has been found in patients who received blood or blood components. Viral DNA was demonstrated in commercial preparations of FVIII and F IX, but very few data have been reported on immunoglobulins. The risk of TTV infection associated with intramuscular or IV immunoglobulin administration is unclear. STUDY DESIGN AND METHODS: The prevalence of TTV infection in a group of patients undergoing lifelong therapy because of congenital immunodeficiency has been evaluated in a long term follow up (median, 6 years). Seventeen patients with congenital immunodeficiency receiving monthly administration of IVIG were included in the study. TTV DNA was repeatedly evaluated by PCR in serum samples from each patient during the follow up. Research of antibodies against TTV was not applicable, as the patients studied were unable to produce antibodies. The presence of TTV was also evaluated in 15 IVIG lots. RESULTS: The total amount of immunoglobulin administered was 18,773 g. TTV infection was not found in any patients included in the study. None of the 15 immunoglobulin preparations analyzed was found positive for TTV DNA. CONCLUSION: Despite the high prevalence of TTV in blood donors, commercial immunoglobulins are safe and unable to transmit TTV. PMID- 11778065 TI - C-reactive protein and IL-6: new marker proteins for the diagnosis of CJD in plasma? AB - BACKGROUND: CJD is usually diagnosed by clinical and neuropathological findings. A number of proteins regarded as markers for neuronal damage in plasma or serum have recently been described. Markers typical for tissue damage, although not usually associated with CJD, are another possibility. An evaluation of the relative usefulness of markers of neuronal and tissue damage in identifying CJD could be beneficial. STUDY DESIGN AND METHODS: Plasma samples were collected from 46 patients with sporadic CJD and from a control group of 42 healthy subjects. The samples were analyzed with tests that were specific for C-reactive protein (CRP), IL-6, neuron-specific enolase (NSE), S-100 proteins, and cellular prion protein (PrP(c)). The results were compared, and a cutoff level for each test used was defined as the 90th percentile from the control group. RESULTS: The assay specific for NSE identified only 13 percent of the sporadic CJD patients as positive. The identification rate of the other markers was significantly higher: S-100, 76.1 percent; PrP(c), 76.1 percent; CRP, 78.3 percent; and IL-6, 73.3 percent. Only three of the samples were positive in all five tests. CONCLUSION: The markers for tissue damage, CRP and IL-6, are as useful as the previously described markers for neuronal damage in the diagnosis of CJD in plasma. All the markers tested are, however, of only limited value in the diagnosis of CJD in plasma. A combination of all surrogate markers improves the specificity but still provides no definitive diagnosis of the disease. PMID- 11778066 TI - The effect of the transfusion of stored RBCs on intestinal microvascular oxygenation in the rat. AB - BACKGROUND: Although it is known that the transfusion of stored RBCs does not always improve tissue O(2) consumption under conditions of limited tissue oxygenation, the efficiency of O(2) delivery to the microcirculation by stored RBCs has never been determined. STUDY DESIGN AND METHODS: In a rat hemorrhagic shock model, the effects of resuscitation with fresh or 28-day-old RBCs stored in CPD plasma, saline-adenine-glucose-mannitol, and CPDA-1 plasma were investigated. Systemic hemodynamic and intestinal oxygenation measures were monitored. Intestinal microvascular PO(2) was determined with the O(2)-dependent quenching of palladium-porphyrin phosphorescence, and the RBC deformability was measured with a Laser-assisted optic rotational cell analyzer. RESULTS: Hemodynamic and oxygenation measures were significantly decreased during hemorrhagic shock. Intestinal oxygen consumption and mesenteric venous pO(2) were restored with the transfusion of both fresh and stored RBCs, except for CPD-stored RBCs. The intestinal microvascular pO(2) improved only with the transfusion of fresh RBCs. Deformability of the stored RBCs was significantly decreased. CONCLUSION: In contrast to that of fresh RBCs, the transfusion of stored RBCs did not restore the microcirculatory oxygenation, possibly because of impaired O(2) unloading, but, except for CPD-stored RBCs, the storage-induced changes were not enough to impair intestinal VO(2) and mesenteric venous pO(2). PMID- 11778067 TI - Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. AB - BACKGROUND: Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation. STUDY DESIGN AND METHODS: This study prospectively characterized the kinetics of cellular and cell free fetal DNA in the circulation of 25 healthy women during and after uncomplicated pregnancy. Real-time kinetic PCR was used to quantitate human Y chromosome sequences, and liquid oligomer hybridization with (32)P-labeled probes was used to verify the identity of amplified products. RESULTS: In all male pregnancies, but no female pregnancies, low-level fetal Y-chromosome DNA was detected in both cellular and cell-free compartments beginning at 7 to 16 weeks but increasing steadily after 24 weeks and reaching a peak at parturition. The fetal DNA decreased rapidly after birth. CONCLUSION: Fetal genetic material can be detected throughout pregnancy, and its quantity is a function of gestational age and of whether the plasma or cellular compartment is examined. Both the absolute quantity of fetal DNA and its ratio to total DNA (maternal + fetal) are greater in the plasma than in the cellular compartment. Fetal DNA is cleared rapidly from both compartments after parturition, which suggests that turnover is dynamic. Because they provide prospective and quantitative data concerning fetal DNA levels, these observations and kinetic PCR methods may have implications for noninvasive prenatal diagnosis. Further studies will be needed to determine the immunologic implications of fetal-maternal DNA exchange and cellular microchimerism. PMID- 11778068 TI - Identifying allogeneic platelets by resolution of point mutations in mitochondrial DNA using single-stranded conformational polymorphism PCR. AB - BACKGROUND: The purpose of this study was to evaluate single-stranded conformational polymorphism (SSCP)-PCR utilizing two different regions of mitochondrial DNA (mtDNA) as a method to discriminate between donor platelets and recipient cells. STUDY DESIGN AND METHODS: Twenty-eight mixtures of platelets (1:1 ratio) were prepared from eight randomly selected persons to simulate donor recipient combinations after allogeneic platelet transfusion. The mtDNA was extracted from each donor and each prepared mixture. Four primer pairs were designed to amplify two regions of mtDNA, hypervariable region (HVR) 1 and 2. An SSCP-PCR method was developed to analyze the four different amplicons. In addition, the amplified DNA samples containing HVR1 and HVR2 mtDNA of the eight persons were sequenced by using dye-terminator cycle sequencing to determine mtDNA polymorphisms. RESULTS: With four different primer pairs and SSCP-PCR, it was possible to discriminate between donor and recipient DNA in all 28 combinations. DNA sequencing confirmed that the suspected differences were localized within the amplicons examined by SSCP-PCR. CONCLUSION: SSCP-PCR analysis targeting the HVR1 and HVR2 mtDNA is a promising new method to potentially identify donor cells on the basis of mtDNA polymorphisms. The method does not require prior knowledge of sequence differences between donor and recipient and can be optimized to quantify the amount of residual transfused allogeneic platelets. PMID- 11778069 TI - Autologous blood transfusion in the United States: clinical and nonclinical determinants of use. AB - BACKGROUND: Preoperative donation of blood lowers the risk of allogeneic RBC transfusion. The use of autologous blood is not well quantified. This study aimed at identifying the frequency and determinants of use of autologous transfusion in the United States. STUDY DESIGN AND METHODS: This national cross-sectional study, using the Nationwide Inpatient Sample, included all patients admitted to 900 hospitals in 19 states in 1996. Logistic regression with weighting yielded nationally representative results for the independent effects of clinical and nonclinical patient characteristics on autologous blood use. RESULTS: Autologous transfusion was used in 19 of 1000 hospitalizations. The procedures using autologous blood most frequently were knee arthroplasty, hip replacement, prostatectomy, spinal fusion, and hysterectomy. Blacks and Hispanics were less likely to receive autologous transfusion than were whites (OR, 0. 64; 95% CI, 0.45-0.83); patients with Medicaid were less likely than the privately insured to receive autologous transfusions (OR, 0.29; 95% CI, 0.20-0.43), with racial differences greatest among the privately insured. Women received autologous blood for cardiovascular surgeries much less often than men (OR, 0.32; 95% CI, 0.20 0.49). CONCLUSION: Ethnic minorities, women, and patients with Medicaid appear to receive fewer autologous blood transfusions than the rest of the population. Although this could reflect either better or worse quality of care, nonclinical determinants of transfusion practice warrant attention and further investigation. PMID- 11778070 TI - Transfusing methylene blue-photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate. AB - BACKGROUND: Photodynamic virus inactivation of plasma with methylene blue significantly decreases the recovery of fibrinogen and coagulation factors V and VIII. Because an adequate supply of fibrinogen is essential for the therapeutic efficacy of transfused plasma in many clinical settings, it was plausible that transfusing photoinactivated plasma (PIP) instead of FFP would result in an increased demand for plasma and cryoprecipitate. STUDY DESIGN AND METHODS: The study involved a retrospective analysis of the use of plasma at a university hospital (Barcelona, Spain) over three 1-year periods: one before the implementation of PIP therapy and two after. Blood components transfused to plasma recipients were listed by broad diagnostic categories based on the Diagnosis-Related Group classification. RESULTS: During the period under study, 2,967 patients were given plasma in this hospital. They received 27,434 units of plasma, 1,660 of cryoprecipitate, 10,079 of platelets, and 24,607 of packed RBCs. Patients undergoing surgical procedures accounted for 74 percent of all transfused plasma. In 71 percent of patient admissions, packed RBCs were transfused in addition to plasma. Diagnostic categories with the greatest requirement for plasma were cardiac valve surgery, liver transplant, wounds and traumatic injuries, and bowel surgery. The use of PIP was associated with a 56 percent increase in the aggregated demand for plasma, whereas the transfusion of non-virus-inactivated cryoprecipitate increased twofold the first year and threefold the second year. The growth in the use of plasma took place in all the diagnostic categories. In those categories that include patients with liver disease, a partial substitution of PIP for cryoprecipitate was observed during the second year after PIP therapy implementation. CONCLUSION: The use of PIP was associated with a marked increase in the demand for plasma and cryoprecipitate, which probably was due to the low hemostatic quality of the new component. It is possible that such an increase overrode the potential health benefits derived from transfusing virus-inactivated plasma. PMID- 11778071 TI - The use of genotyping to predict the phenotypes of human platelet antigens 1 through 5 and of neutrophil antigens in Taiwan. AB - BACKGROUND: The human platelet antigen (HPA) 1 through 5 and the human neutrophil antigen (HNA-1) systems are relevant to immune-related thrombocytopenia and neutropenia. The alloantigen distribution profiles in the population will aid in estimating the risk of alloimmunization. STUDY DESIGN AND METHODS: Genotyping of the genes that control the expression of the HPA-1 through -5 and HNA-1 systems in Taiwanese (n = 326) and Taiwan's indigenous peoples (n = 608) was performed by PCR with the sequence-specific primer (PCR-SSP) method. RESULTS: In the HPA system, HPA-1b and HPA-4b were absent among Taiwan's indigenous tribes and detected among other Taiwanese only with frequencies of <0.2 percent and <0.5 percent, respectively. The GP1BA*2 (HPA-2b) and GP1A*2 (HPA-5b) allele frequencies range from 1 percent to 7 percent and 0.4 percent to 3.5 percent among the two ethnic groups, respectively. GP2B*1 (HPA-3a) and GP2B*2 (HPA-3b) showed similar allele frequencies. In the HNA-1 system, the FCGR3B*1 (HNA-1a) allele frequency was about twice that of FCGR3B*2 (HNA-1b) in Taiwanese and also in most of the indigenous tribes. Three FCGR3B (HNA-1) null persons were found in one indigenous tribe (Ami tribe), for an FCGR3B null frequency of 19.8 percent. However, no FCGR3B*3 (HNA-1c) allele was detected in Taiwan. CONCLUSION: The frequencies of HPA-1b, -2b, and -5b in the Taiwanese population were much lower than those among whites. In Taiwan, all of the HNA-1 null found was due to the deletion of the FCGR3B gene, and this deletion may be widely distributed in the Ami tribe. PMID- 11778072 TI - Increased RBC autoantibody production in pregnancy. AB - BACKGROUND: Autoimmunization against RBCs is generally believed to occur very rarely during pregnancy and to represent a high risk for those affected. The occurrence of benign RBC autoantibodies in pregnancy is reported. STUDY DESIGN AND METHODS: The incidence of autoantibodies to RBCs in unselected pregnant and nonpregnant women were compared by the new standard gel hemagglutination method. RESULTS: Data from a total of 22,782 pregnant and 12,903 nonpregnant women were analyzed. The antibody screen test was positive in 547 (2.40%) of the pregnant women. The positive test results were related to passive anti-D in 341 cases (1.50%), to clinically relevant alloantibodies in 43 cases (0.19%), to clinically irrelevant antibodies in 138 cases (0.61%), to autoantibodies in 23 cases (0.1%), and to autoantibodies plus alloantibodies in 2 cases (0.01%). In the cases of alloantibodies and/or autoantibodies, the DAT was invariably positive with anti C3d and less commonly so with anti-IgG. The autoantibodies were first detected during pregnancy, they predominantly reacted with enzyme-treated RBCs, and none of the affected women or their infants appear to have developed clinically significant hemolysis. In the control group consisting of nonpregnant female blood donors, there were 3 cases (0.02%) of clinically insignificant IgG autoantibodies. CONCLUSION: There is an increase in autoimmunization against RBCs during pregnancy. The resultant autoantibodies do not appear to cause significant RBC destruction. Further studies are required for precise characterization of this phenomenon. PMID- 11778073 TI - Comparison of intermittent- and continuous-flow cell separators for the collection of autologous peripheral blood progenitor cells in patients with hematologic malignancies. AB - BACKGROUND: The transplantation of autologous peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy is a valuable therapy for patients with hematologic and solid malignancies. Several methods are used for harvesting PBPCs. The efficiency of intermittent- and continuous-flow blood cell separators in collecting progenitor cells from the blood of patients undergoing myeloablative treatment for cancer was compared. STUDY DESIGN AND METHODS: PBPC components (n = 133) were obtained from 72 patients by leukapheresis with continuous-flow machines (Spectra, COBE; CS 3000 Plus, Baxter) and with an intermittent-flow machine (MCS 3P, Haemonetics). The data were analyzed retrospectively. Blood samples obtained from the patients before leukapheresis and samples of the leukapheresis components themselves were analyzed for their content of RBCs, WBCs, platelets, and CD34+ cells. RESULTS: The Spectra processed more than twice the blood volume in the shortest time (15 L in 178 min), whereas the Baxter CS 3000 Plus (10 L in 185 min) and the MCS 3P (4.8 L in 239 min) processed significantly smaller volumes in a longer time. The mean ACD consumption was 403 mL with the MCS 3P, 900 mL with the CS 3000 Plus, and 1000 mL with the Spectra. The product volumes were 50 mL (CS 3000 Plus), 69 mL (MCS 3P), and 166 mL (Spectra). In all groups, differences in the preapheresis hemograms were not significant, but the Spectra group had fewer CD34+ cells than the other groups. Despite this, the differences in the number of CD34+ cells in the leukapheresis components of all groups were without statistical significance. In the Spectra group, the collection of MNCs of 104 percent and CD34+ cells of 154 percent was significantly more efficient than that in the MCS 3P group (42.2% and 56%, respectively) or the CS 3000 Plus group (50.8% and 47.15%) as related to the patients' blood volume. CONCLUSION: PBPC collection can be performed successfully with continuous-flow and intermittent-flow blood cell separators. The Spectra had the best recovery of CD34+ cells within the shortest time. Leukapheresis with the MCS 3P is indicated if only a single venous access is available. PMID- 11778074 TI - Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice. AB - BACKGROUND: Ex vivo expansion of cord blood (CB) hematopoietic stem and progenitor cells increases cell dose and may reduce the severity and duration of neutropenia and thrombocytopenia after transplantation. This study's purpose was to establish a clinically applicable culture system by investigating the use of cytokines, serum-free media, and autologous plasma for the expansion of CB cells and the engraftment of expanded product in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. STUDY DESIGN AND METHODS: Enriched CB CD34+ cells were cultured in four media (Iscove's modified Dulbecco's medium with FCS, Gibco; X-Vivo-10, BioWhittaker; QBSF-60, Quality Biological; and StemSpan SFEM, Stem Cell Technologies) with four cytokine combinations (thrombopoietin [TPO], SCF, Flt-3 ligand [FL] with and without G-CSF, and/or IL-6). The effect of autologous CB plasma was also investigated. The read-out measures were evaluated on Days 8 and 12. After expansion at the optimized condition, cultured cells were transplanted into sublethally irradiated NOD/SCID mice. The engraftment of human CD45+ cells and subsets in the bone marrow, spleen, and peripheral blood was determined. RESULTS: QBSF-60 or StemSpan SFEM supported high yields of early progenitors (CD34+ cells, 5 log concentration range, allowing pre-WBC-reduction and post-WBC reduction comparisons. Sensitivity limits ranged from 10 cells per mL (CD45) to 200 cells per mL (CD19). Assay specificity was confirmed by the close correlation of real-time RT-PCR and immunophenotyping results by flow cytometry. For all subsets, >3.8 log and >3.1 log reduction was obtained during WBC reduction of whole blood and platelets, respectively. CONCLUSION: Real-time RT-PCR assays are suitable for analysis of subset removal during WBC reduction. There was no significant difference between the two whole-blood filters or between platelet filtration and apheresis in the removal of any WBC subset. PMID- 11778078 TI - The impact of the intensity of serial automated plasmapheresis and the speed of deep-freezing on the quality of plasma. AB - BACKGROUND: Data are lacking on the impact that the intensity of serial donor plasmapheresis has on the quality of source plasma. A study was conducted to examine the quality of source plasma produced by intensive plasmapheresis and slow deep-freezing and to compare it to source plasma manufactured by moderate plasmapheresis and rapid freezing. STUDY DESIGN AND METHODS: Seventy-five plasma samples from intensive plasmapheresis programs (Group 1) and 75 plasma units from moderate plasmapheresis programs (Group 2) were examined. The plasma had been deep-frozen either slowly at -30 degrees C in walk-in freezers (Group 1) or rapidly within 1 hour to a core temperature below -30 degrees C (Group 2). Determinations were made of the plasma levels of citrate; total protein; albumin; IgG; fibrinogen; factors II, V, VII, VIII, and IX; vWF; antithrombin; protein C; D-dimers; and prothrombin fragments 1+ 2. RESULTS: Plasma units of Group 2 contained substantially greater levels of citrate, IgG, FVIII, and FV than samples of Group 1 (p<0.0001). Plasma levels of total protein, albumin, and fibrinogen also were higher in Group 2 (p<0.0001, p = 0.007, and p = 0.006, respectively). Neither plasmapheresis intensity nor freezing procedure had any influence on the levels of factors II, VII, and IX, antithrombin, or protein C. There was no evidence of substantial coagulation activation in the plasma units of either group. However, higher FVIII clotting activity/chromogenic substrate activity ratios in rapidly frozen plasmas and a significant correlation between these ratios and prothrombin fragment 1+ 2 levels suggest that rapid freezing yields both more native FVIII and greater partial activation of FVIII. CONCLUSION: Source plasma collected from donors undergoing intensified plasmapheresis contains markedly lower levels of IgG than plasma units produced by moderate serial plasmapheresis. The combination of intensified plasmapheresis and slower freezing of source plasma results in substantially lower levels of FV and FVIII than does moderate plasmapheresis with rapid freezing. Prospective studies should establish the optimum conditions required for the safe and economic production of source plasma for fractionation. PMID- 11778079 TI - Effects of different concentrations of anticoagulant on the in vitro characteristics of autologous whole blood. AB - BACKGROUND: Routinely, 450 mL of blood is collected into 63 mL of CPDA-1, for a final anticoagulant:blood ratio of approximately 1:7 in a whole-blood autologous unit. If less than 300 mL of blood is to be collected, the AABB standards suggest that there should be a proportionate decrease in anticoagulant. Data from an autologous blood program showed a range in volume from 92 mL to 667 mL per bag, which reflects an anticoagulant:blood ratio of 2:1 to 1:10. STUDY DESIGN AND METHODS: To determine the effects of these ratios on the in vitro function of RBCs at various anticoagulant ratios, blood was collected into different amounts of anticoagulant, and various measurements were made during storage. RESULTS: The number of RBCs and the MCV remained constant over time, regardless of the anticoagulant dilution used. Plasma free Hb increased with time with all dilutions. At a 1:2 ratio, it rose from 734 mg per L on Day 1 to 1805 mg per L on Day 35, and at 1:8, it was 355 mg per L for Day 1 and 854 mg per L on Day 35. Plasma sodium decreased and the potassium increased over time with all dilutions. From Day 1 to Day 35, there was a nine-fold increase in potassium at both the 1:2 and 1:8 dilutions (2.4 to 22.9 mmol/L, 3.2 to 29.6 mmol/L, respectively). The LDH increased over time and the pH decreased in all of the dilutions. Osmotic fragility remained constant at the 1:8 dilution but decreased at all of the other dilutions with storage, with 44-percent fragility on Day 35 at the 1:2 ratio. The WBC and platelet counts decreased consistently over time. Overall, 1 percent of the autologous units were below the cutoff volume of 300 mL at which an adjustment of the anticoagulant volume is required. CONCLUSION: Plasma Hb and plasma potassium concentrations are considerably higher in low-volume units, which indicates that deviation from standard collection procedures is deleterious to RBCs. PMID- 11778080 TI - Implementation of a blood irradiation program at a community cancer center. AB - BACKGROUND: Blood component irradiation is an accepted method of preventing transfusion-associated GVHD. Previous publications have largely focused on the technical aspects of the irradiation process itself, but relatively little attention has been paid to the details associated with the implementation of a blood irradiation program at the level of a community cancer center. STUDY DESIGN AND METHODS: An observational study was performed, detailing the specific operational, documentation, and quality assurance measures employed in providing a blood component-irradiation service within the institutional context of a community cancer center. RESULTS: The Montgomery Cancer Center irradiated 589 units of blood components in 1998 and 1999 to provide a local blood bank with an alternative for procurement of irradiated blood components while complying with applicable quality assurance and regulatory requirements. CONCLUSION: Blood component irradiation is within the scope of most well-equipped and adequately staffed community cancer centers. Establishment of a blood component irradiation program requires scrupulous physics and dosimetry support, both to ensure the quality of the irradiated component and to satisfy governmental agency regulatory requirements. PMID- 11778081 TI - Economy of platelet transfusions from a hospital perspective: pricing predicates practice. PMID- 11778082 TI - Misclassification of HCV-viremic blood donors as indeterminate by RIBA 3.0 because of human superoxide dismutase reactivity. PMID- 11778083 TI - False-positive HLA antibody screen associated with Campath administration. PMID- 11778085 TI - New trends in regional anaesthesia. AB - In this review, some of the newer developments in regional anaesthesia (RA) are discussed. The relationship between paraesthesiae and nerve stimulator responses has been shown to be unclear, and sometimes at a needle tip location where a paraesthesia is found, there is no response to the nerve stimulator. It is recommended to use whichever end point is found first. The debate as to the safety of RA in anaesthetised patients remains unresolved and strong opinions are often based on individual case reports. The training and skill of the anaesthetist still appears to be a more important factor. The problems of RA and impaired coagulation are well understood and guidelines are in place in many countries. The value of neuraxial blocks for postoperative pain management is well established and the increasing use of peripheral nerve blocks often using continuous methods is to be encouraged. The use of PCA for blocks as well as intravenously and the extension of the use of RA into the home are important developments. The beneficial effects of RA on postoperative morbidity and mortality are becoming clearer, and the introduction of the two new local anaesthetic agents, ropivacaine and levobupivacaine have improved safety. There has, however, been very slow progress in the development of long awaited ultralong acting local anaesthetics or in the introduction of slow release formulations. PMID- 11778084 TI - On the treatment of hemorrhage in patients with hemophilia and associated inhibitors. PMID- 11778086 TI - Mepivacaine: update on an evergreen local anaesthetic. AB - Many local anaesthetics are presently available for clinical use. The choice of a particular agent for a particular regional anaesthetic is based mainly on its clinical and pharmacological features. Besides these, safety of drugs and the knowledge of side effects associated with their use can play a major role, since serious complications can be related to local anaesthetics administration. Pharmacologic features of mepivacaine are: its amide structure (therefore it is not detoxified by circulating plasma esterases), its rapid metabolism, which take place into the liver, and its rapid excretion via the kidneys. Clinically, mepivacaine shows: short onset time, very close to lidocaine, intermediate duration and low toxicity. Mepivacaine can be therefore considered as a first choice agent for peripheral nerve blocks, particularly in high cardiac risk patients. PMID- 11778087 TI - Best indications for local anaesthetics: bupivacaine. AB - Bupivacaine is a local anaesthetic of great potency and long duration but has also well known cardio-and CNS toxic side-effects. For many years it was nearby the only local anaesthetic with these characteristics, making it applicable to almost all kind of loco-regional anaesthetic techniques, and still nowadays, for economical reasons it is in many occasions the only alternative available. In this review, departing from analysis of the physical, chemical and pharmacological properties of this molecule and considering also its toxic potencies we wanted to analyze all clinical situations in which it is used. But above all we have reviewed the most recent international literature, which are actually the best indications for this drug, that in the last years with the appearance of first ropivacaine and then levobupivacaine, seemed to have lost its field of elective application. According to these analysis we concluded that this drug, though still remaining a good alternative in many fields of loco-regional anaesthesia (like peripheral blocks), as well as an efficient drug equal to the above mentioned ones in any sector like epidural analgesia in caesarean section, its best indication is subarachnoideal anaesthesia (combined and not) where it is the best available drug in hyperbaric solution without doubts. It might be interesting in the next future the comparison with hyperbaric solutions of levobupivacaine (not yet available). PMID- 11778088 TI - Ropivacaine. AB - BACKGROUND: Ropivacaine is a relatively new long-acting local anesthetic. It is a pure S(-) isomer, with a high pKa and low lipid solubility. Because of its physical and chemical properties, ropivacaine produces a marked differential in sensory and motor blockades, with a toxic potential lower than other long-acting anesthetic solutions. The purpose of this paper was the evaluation of the literature concerning indications and advantages of ropivacaine for different regional anesthesia techniques. METHODS: We have evaluated results of prospective, randomized, controlled trials evaluating clinical use of ropivacaine for epidural anesthesia and analgesia, as well as spinal and peripheral nerve blocks. RESULTS: The literature clearly demonstrates both efficacy and safety of ropivacaine used for epidural anesthesia and analgesia as well as for upper and lower limb peripheral nerve blocks, both single-shot and continuous peripheral blocks. Although ropivacaine has not been registered yet for spinal anesthesia, various studies show its efficacy and safety also in this field. Because of its pharmacodynamic properties, intrathecal ropivacaine seems also interesting for outpatient procedures. CONCLUSIONS: Ropivacaine is a long-acting local anesthetic with a marked differential blockade between sensory and motor fibres, overall at the low concentrations used for postoperative analgesia. It probably has a slightly lower potency as compared with bupivacaine, but provides similar clinical efficacy in the different fields of regional anesthesia. Ropivacaine is less cardiotoxic and causes less central nervous system toxicity than bupivacaine, and this lower toxic potential has been reported not only with equivalent but also with equipotent concentrations and doses. For this reason, ropivacaine represents a useful alternative to bupivacaine for central and peripheral nerve blocks as well as for the management of postoperative pain relief. PMID- 11778089 TI - Levobupivacaine. AB - Bupivacaine has been the most widely used local anaesthetic for years. Recent studies point out levobupivacaine, an S(-) isomer of the racemic bupivacaine. This review shows the properties of levobupivacaine describing the animal and human volunteers studies on toxicity and the first clinical studies in obstetrics, general surgery and paediatrics. In vitro animal studies show that, injected intravenously, levobupivacaine has less cardiotoxic effects and less toxic effects on the CNS in comparison with both R(+) bupivacaine and bupivacaine itself, caused by a minor affinity for brain tissue resulting in less CNS depressant effects as well as for myocardial tissue, which leads to a higher dose necessary before being lethal in comparison to bupivacaine. Studies in human volunteers confirm these results, adding a minor arrhythmogenic, and less negative inotropic effect. Clinical studies show no significant differences in onset, duration and sensory block, but complete regression of sensory block takes longer. Potency is equal for levo- and bupivacaine according to MLAC in labour analgesia. Studies in paediatrics confirm effective analgesia but show less intensity of motor block. The reduced toxicity of levobupivacaine gives wider safety margin in the daily clinical practice both for single shot and for continuous infusion, intraoperatively during various surgical procedures and for the postoperative pain control and analgesia in labour. PMID- 11778090 TI - [Levobupivacaine in obstetric analgesia and anaesthesia]. AB - METHODS: Published studies, including abstracts, has been reviewed and summarized. RESULTS: Studies in sheep have demonstrated no significant differences in pharmacokinetic and placental transfer of levobuvacaine when compared with bupivacaine. Clinical studies on cesarean section confirmed similar performance between these two drugs. No differences in onset time, sensory and motor block and efficacy of analgesia have been reported. Two multicentre studies on labor analgesia reported again similar analgesic efficacy with a trend toward less motor block in parturients receiving levobupivacaine. CONCLUSIONS: This review has shown that levobupivacaine has a similar efficacy and a similar maternal fetal safety to that of bupivacaine. Further studies are needed to determine if the chemical properties of the new agent may influence the sensory and motor characteristics of the block. PMID- 11778091 TI - [Motor block determination for the identification of accidental spinal injection of levobupivacaine: a study on the minimum efficient test-dose (ED50)]. AB - BACKGROUND: The aim of this study was to determine the ED50 for the dose of levobupivacaine 0,5% that, if given intrathecally will not cause total spinal anesthesia but will give a reliable and reproducible clinical sign to differentiate intrathecal from epidural injection. METHODS: Thirty women at term undergoing elective cesarean section under a combined spinal-epidural technique (CSE) were enrolled into this sequential allocation study. The dose in each test dose was determined by the response of the previous patient to the higher or lower dose in her test syringe, according to up-down sequential allocation. The exception to this was the first woman in each group, for whom the starting dose was chosen to be 4 mg. The end point was the occurrence of any motor block, in any side, within 5 minutes from intrathecal injection of the test dose. Test dose efficacy was assessed using a modified Bromage scale every minute for 5 minutes. The median effective dose of levobupivacaine was estimated from the up-down sequences using the formula of Dixon and Massey. RESULTS: The MAD of the test dose for levobupivacaine was of 4,8 mg (4,4 to 5,2; 95% C.I.). DISCUSSIONS: This study may help to determine the appropriate dose for a test dose for inadvertent spinal levobupivacaine. PMID- 11778092 TI - [Levobupivacaine for peripheral blocks of the lower limb: a clinical comparison with bupivacaine and ropivacaine]. AB - BACKGROUND: The aim of this study was the comparison of clinical profile of sciatic nerve block performed with either 0,5% levobupivacaine, 0,5% bupivacaine, or 0,5% ropivacaine. METHODS: With ethical committee approval and written informed consent 45 ASA physical status I-II patients, undergoing elective hallux valgus repair received intravenous premedication with midazolam (0,05 mg/kg) followed by femoral nerve block with 15 ml of 2% mepivacaine. Then patients were randomly allocated to receive a sciatic nerve block with 20 ml of either 0,5% levobupivacaine (n=15), 0,5% bupivacaine (n=15), or 0,5% ropivacaine (n=15). An independent blind observer evaluated the onset time and duration of nerve block and postoperative analgesia. Postoperative analgesia consisted of 100 mg IV ketoprofen every 8 hours with the first administration at request. RESULTS: The onset time of sciatic nerve block was 15 (5-60) min with levobupivacaine, 30 (5 60) min with bupivacaine, and 15 (5-60) min with ropivacaine (P = NS). No differences in the quality of nerve block as well as in the nerve block resolution times were observed among the three groups. The duration of postoperative analgesia was 16 (8-24) hours with levobupivacaine, 14 (8-24) hours with bupivacaine, and 17 (8-24) hours with ropivacaine (P=NS). CONCLUSIONS: Using 0,5% levobupivacaine for sciatic nerve block results in similar clinical effects as those produced by using the same volume and concentration of either bupivacaine or ropivacaine. PMID- 11778093 TI - [S(-) bupivacaine (levobupivacaine) in peripheral blocks: preliminary results]. AB - We have compared the onset time, anesthetic potency and adverse effects of three local anaesthetics (ropivacaine, levobupivacaine and bupivacaine) in two type of peripheral blocks (brachial plexus block for upper limb and femoral nerve block for lower limb) in adult patients in a double blind, randomized, prospective study. A total of 66 patients undergoing orthopaedic surgery were randomly allocated to receive brachial plexus block or femoral nerve blockade with 0,5% ropivacaine (group R, n=22), 0,5% levobupivacaine (group L, n=22) or 0,5% bupivacaine (group B, n=22), each groups has been divided into two subgroups (LBP n=11, RBP n=11, BPB n=11, LBF n=11, RBF n=11, BBF n=11) dipending on the type of block. The onset of sensory nerve block was similar for the three groups; the onset of motor block and onset time ready to surgery were faster in group R ( 30%) if compared with group L and B. The duration of motor block and sensory block was respectively longer in group L and in group B. Study results have not been influenced by the blocks, except for plexus nerve block where we observed the same results for group B and group R in relation to onset time ready to surgery. VRS scores were higher in group R as showed by the number of analgesic request in postoperative period. We did not observe any adverse effect. We conclude that ropivacaine acts faster with less interpatient variability, while levobupivacaine and bupivacaine offer a prolonged postoperative analgesia. For this reason, with the exception of bupivacaine due to major cardio and neuro toxicity, we can indifferently use levobupivacaine or ropivacaine depending on the requested characteristics of the anesthetic. PMID- 11778094 TI - [Brachial plexus block. The anaesthetic line is a guide for new approaches]. AB - Brachial plexus blockade is one of the most widespread technique in regional anaesthesia. Many Authors presented different approaches to the plexus, following different routes, over or under the clavicle related to near landmarks, paresthesia or electrical nerve stimulation. The Author presents an anatomical perspective to guide the localization of the brachial plexus, following an anaesthetic line created by linking together several landmarks, generally used in few number for single approach techniques, over or under the clavicle. The line leaves from the apex of the scalene triangle, through the middle point of the clavicle, the middle point between the coracoid process and the chest profile, and arrives to the pulsation of the axillary artery, when the arm is abducted at 45 degrees. This general view favours a better understanding of the placement of the brachial plexus, following the anatomical guide developed from the anaesthetic line; thus the placement of the needle, from distal to proximal, in a vertical or tangential route towards the nerve structures becomes clearer, showing the different entry point in a simple and efficacious way. The same technique may apply to the infraclavicular approach, favouring the vertical approach or a tangential one, when catheterisation is needed. PMID- 11778095 TI - [Sopraclavicular techniques for brachial plexus block]. AB - BACKGROUND: Aim of the present study is to review the four different methods of brachial plexus block, with supraclavicular approach, which have reached the higher approval or given less side effects. METHODS: The Author reviewed the following techniques: Kulenkampff's (1911), Winnie's (1970), Brown's (1988) and Alemanno's (1992). CONCLUSIONS: The four methods that were presented in the last century differ not for the results, which are more or less the same, but for the possible side effects, which result to be less with the latest techniques. PMID- 11778096 TI - [Loco-regional anaesthesia of the lower limbs]. AB - Lumbar plexus and sacral plexus are responsible for sensory and motor innervation of the whole inferior limb and their blockade can be used as a single technique or integrated with general anaesthesia for hip-, femur-, knee-, lower leg-, ankle and foot surgery. For the performance of the blocks, knowledge of peripheral and central percourse of the nerves and their anatomical relationships to bone-, muscle-, vessel and skin structures is important. In case of the sciatic nerve, a cutaneous projection of the percourse of the nerve is possible (the so-called sciatic line) formed by a virtual line from the midpoint of the line between great trochanter and ischial tuberosity to the apex of the popliteal fossa. Peripheral blocks used for the above mentioned types of surgery are: lumbar plexus block, sacral plexus block, femoral nerve block, obturator nerve block, lateral cutaneous femoral nerve block and sciatic nerve block. Regarding the last one, the following approaches are possible, depending on the anatomical site of performance: classic proximal posterior block, parasacral proximal block, lithotomic posterior proximal block, subgluteal posterior proximal block, anterior proximal block, lateral medio femoral popliteal proximal block, block distal from the poplitea, subcalcaneal block. The terms distal and proximal are in relation to the small trochanter. All blocks have to be performed using a nerve stimulator, teflon insulated needles of various measures depending on the kind of block, variable stimulation from 1,5 mA (when evoking muscle contraction) to 0,5-0,3 mA (injection of local anaesthetic) with frequencies of 2 Hz/0,1 ms. PMID- 11778097 TI - [Cervical plexus block and continuous cervical peridural block with ropivacaine for carotid surgery: a comparison between the 2 methods]. AB - OBJECTIVE: To evaluate the efficacy and security of the cervical plexus block and the continuous cervical peridural anaesthesia in carotid surgery, using ropivacaine as local anaesthetic. METHODS: 90 patients (ASA II-III, age 67-84) who had signed informed consent were randomised in two groups. In Group C continuous cervical plexus block was performed using ropivacaine 0,75% 2,5 mg/kg. In Group P continuous cervical peridural anaesthesia was performed, at level C6 C7 or C7-T1, introducing the catheter for 5 cm into the epidural space and injecting in 20 min ropicavacine 0,5% 0,9 mg/kg together with 50-100 g of fentanyl. ECG, HR, arterial blood pressure, neurological status of conscious patient and eventual complications were all monitored. RESULTS: Demographical data, duration of surgery and level of anaesthesia were all uniform in both groups. At the onset of the block the values of the systolic arterial blood pressure were significantly lower in Group P compared to Group C. One case of intradural injection of ropivacaine was reported and one case of intravascular injection, without remaining deficits. There were no perioperative complications. CONCLUSIONS: cervical plexus block and continuous cervical peridural anaesthesia performed with ropivacaine are both effective for anaesthesia in carotid surgery. Ropivacaine, for its minor cardiotoxicity, yields eventual complications related to the two methods, less severe. PMID- 11778098 TI - [Thromboembolic prophylaxis and central blocks]. AB - Epidural and spinal blocks are widely used in several surgical settings in order to obtain analgesic advantages and reduce blood loss and thromboembolic complications. However, many high risk patients receive perioperatively some anti coagulant treatments for preventing venous thrombosis and pulmonary embolism. Although a number of large observations has demonstrated a very low rate of major neurological impairment due to spinal haematomas, in the last years an increasing number of case reports seems to cause an excessive anxiety to the anaesthesiologists. On the other hand, spinal haematomas occurred in same cases without anti-coagulant therapy. An other question concerns the onset time from an epidural/spinal puncture and the development of neurological symptoms of spinal compression, which may appear even after days or weeks. Female gender, aged patients, vascular surgery, uncontrolled positions on the table, number of spinal punctures, large gauge of needle and low degree of skill are the main factors involving in the haemorrhagic phenomena around spinal cord. Accurate anamnesis, no anti-coagulant medication before surgery, and a perfect technique of managing spinal/epidural block are essential elements for reducing probability of severe bleeding and consequent expansive haematomas. Also, informed consent of patients and careful judgement of advantages vs risks of a central block for every high risk case determine the final decision about the regional anaesthesia: to do or not to do. PMID- 11778099 TI - [From heparin to synthetic antithrombotic drugs]. AB - Low molecular weight heparins (LMWH) have become the reference drugs for the prevention and treatment of venous thromboembolism. Among the newer antithrombotic agents, the pentasaccharide is the most advanced and promising alternative of low molecular weight heparins. The pentasaccharide is a synthetic and specific inhibitor of activated coagulation factor X (factor Xa). The pentasaccharide is identical to the active sequence of heparin which is present in about a third of commercially available heparin mixtures. The pentasaccharide binds specifically to antithrombin III (ATIII) thus potentiating its inhibitory activity on factor Xa. As a result, thrombin generation and the formation of fibrin and thus of thrombi is inhibited. After a large phase II dose finding clinical trial, four large clinical trials with pentasaccharide in the prevention of venous thromboembolism in hip or knee surgery have been conducted in Europe and North America. The results of these trials show that pentasaccharide prevents venous thromboembolism to a larger extent than enoxaparine with an overall risk reduction of 50% and no significant increase in bleeding. Among newer antithrombotic drugs, an oral, direct thrombin inhibitor, ximelagatran, has been developed and evaluated in the prophylaxis of venous thromboembolism in hip or knee surgery in comparison with enoxaparine with promising RESULTS. Oral direct thrombin inhibitors have the advantage of predictable dose response with the possibility of oral administration without laboratory monitoring. PMID- 11778100 TI - Diagnosis and therapy of intrathecal bleeding. AB - AIM: Define pathophysiology, epidemiology, diagnosis and therapy in case of spinal bleeding after central neural blockade (CNB). METHODS: Spinal epidural hematoma (SEH) following CNB may occur due to vascular trauma from needle/catheter placement and can occur in subdural and epidural spaces. Epidural artery bleeding seems the source of SEH: the damage mechanism depends on compression and neural vascular ischemia of cord, nerve roots, ganglion and toxicity from blood cell lysis products. Incidence varies (1:150.000 - 1:500.000) but SEH may be asymptomatic. CONCLUSIONS: SEH starts with acute severe low back and/or radicular pain and neurologic signs that may progress to paraparesis, sensory loss and sphincter disturbances. After CNB, the only sign of SEH may be an unusually prolonged motor and sensory block. Symptoms may start even 96 hours after CNB and/or removal of the epidural catheter. Neurological recovery is related to severity and speed of preoperative deficits development and surgical decompression. MR imaging features (diagnostic tool of choice), including degree of cord compression, are useful to establish or confirm the diagnosis of SEH but do not influence the management or predict outcome. Hematoma resolution and severity of neurologic impairment has the greatest impact on management and outcome. Preoperative MRI information and intraoperative evidence of subarachnoid hemorrhage (SAH) and CSF leakage is important: SAH worsens outcome for its negative effect on spinal cord and cauda equina. Conservative therapy may be successful in cases with minimal neurologic deficits, despite cord compression. PMID- 11778101 TI - [Continuous brachial plexus blockade for shoulder surgery]. AB - Continuous brachial plexus block is the technique of choice for postoperative shoulder pain treatment. The localization of the plexus is usually obtained drawing landmarks on the skin and using the electrical nerve stimulator; these and other different modalities are applied in order to reach safely and precisely nerve roots to be blocked with an anaesthetic solution. The Author presents a new anatomical perspective to guide the localization of the brachial plexus. It is shown how it is possible to detect the pathway of the brachial plexus from the cutaneous surface, linking between each other various landmarks: a) the apex of the scalene triangle, at the cross of a line leaving from the cricoid process and directed posterior to the posterior border of the sternocleidomastoid muscle, b) the midline of the clavicle c)the deltoid-pectoral sulcus d) the midpoint between the coracoid process and the chest profile e) the pulsation of the artery in the axylla. Following the guide of the so formed anesthetic line, is possible to place the needle, with a direction from distal to proximal, in a tangential route towards the interscalenic groove, thus allowing to perform a block of the plexus in a simple and efficacious way. PMID- 11778102 TI - [Peripheral blocks for the lower limb: lumbar plexus]. AB - BACKGROUND: The techniques of continuous peripheral blockades have shown to be efficient in postoperative pain control, in the various orthopaedic procedures of the limbs. The aim of this study is to evaluate the existing data about the use of a continuous blockade of the lumbar plexus or femoral nerve, together with the indications for technique and therapy. METHODS: We considered the principal results of prospective, randomised studies described in literature about the assessment of a continuous peripheral blockade of the lumbar plexus or the femoral nerve in limb surgery. Furthermore we described the principal techniques for positioning the perinerval catheters in the considered sites, and the advised dosage regimen. RESULTS: The various studies report an adequate costs/benefits relation concerning the used techniques. The analysed studies not only report an adequate efficacy of the postoperative pain control, but often show an important benefit in terms of functional recovery of the operated limbs and on final outcome of the patient. CONCLUSIONS: The use of continuous blockades of the lumbar plexus or femoral nerve shows to be an important and effective instrument not only in terms of positive effects on postoperative pain control, but also in terms of relevant advantages concerning final outcome after surgery. Nevertheless these techniques should not be considered as the only approach to postoperative pain in the orthopaedic patient, but have to be included in a global, multidisciplinary and multimodal approach. PMID- 11778103 TI - Continuous peripheral block in foot surgery. AB - Peripheral neural blockade techniques are commonly used procedures to provide perioperative anesthesia and analgesia. Several continuous infusion catheter techniques have been described to extend the use of peripheral neural blockade into the postoperative period as an effective method of providing pain management. The analgesic benefit of continuous local anesthetic peripheral block in the management of postoperative pain is primarily related to the properties of providing intense analgesia thereby reducing perioperative opioid requirements and opioid-related side effects and promoting early recovery of postoperative activity. Continuous peripheral nerve blockade seems to be effective in allowing major foot and ankle surgery to be done particularly on an outpatient basis with greater pain relief. The sciatic nerve is the largest nerve in the body and it lies deep in the posterior thigh. According to its anatomy, the sciatic nerve can then be reached at different levels from the parasacral space to the popliteal fossa, ideally identifying a sciatic line running from the inferior border of the gluteus maximus muscle between the greater throcanter and the ischiatic tuberosity to the popliteal fossa. A variety of continuous peripheral blocks have been described in this paper including continuous sciatic block at several levels (para-sacral nerve block, subgluteal sciatic nerve block) and popliteal nerve block. PMID- 11778104 TI - Continuous post-operative regional analgesia at home. AB - OBJECTIVE: Describe early discharge of patients treated with continuous perineural analgesia after orthopaedic surgery. METHODS: A prospective and descriptive study including 56 patients undergoing multiple orthopaedic procedures, who had received oral and written information and given informed consent. Literature on the topic was reviewed, a preliminary study performanced and home nurses were trained. The following blocks were performed: interscalene block (ISKT), infraclavicular block (ICKT), posterior popliteal sciatic block (PPKT) or tibial block at the ankle (TKT). The analgesic catheter (KT) was inserted pre-operatively with nerve stimulation technique. Blockade was induced with mepivacaine and surgery performed under regional anaesthesia. Postoperatively, an elastomeric pump delivering 0.2% ropivacaine(R) at 5 ml/h (tibial blocks) and 7 ml/h (other blocks) was implemented. Analgesic efficacy and side-effects were monitored for 24 hours (patient discharge on Day+1). Pain was evaluated using visual analogical scores (VAS) (0-100) every 12 hours; rescue analgesics were prescribed (propacetamol IV). Nurses ensured patient monitoring at home. Finally, each patient was asked a satisfaction score (0-100). RESULTS: Two patients were excluded. Twenty-one tibial blocks, 24 posterior popliteal sciatic blocks, 6 infraclavicular blocks and 3 interscalene blocks were performed. No major incidents were reported. VAS showed satisfactory post operative analgesia. Median values (max-min) were measured every morning and evening on Day+1 and Day+2. Patient satisfaction was high: 89 (70-100). Hospitalisation costs analysis showed a 46 to 27% decrease in surgery-depending costs. CONCLUSIONS: Continuous, post-operative, perineural analgesia at home is safe and effective, less expensive with high patient satisfaction. PMID- 11778105 TI - [Patient controlled regional analgesia (PCRA) in surgery of stiff elbow: elastomeric vs electronic pump]. AB - BACKGROUND: Aim of this study is to confront an elastomeric pump at regular infusion controlled by the patient with an electronic pump with self administration for analgesia, by continuous infraclavicular brachial plexus block, as support for the intensive postoperative physiotherapy. METHODS: With signed informed consent 10 patients undergoing corrective surgery for stiff elbow were included. All patients received ropivacaine 30 ml 0,50% for anaesthesia by infraclavicular block with bicipite twitch, after which a catheter was left in situ. In group 1 analgesia consisted of ropivacaina 0,4% by electronic pump (continuous infusion with self-administration of bolus) at day1 and day2, and by elastomeric pump at 5 ml/h, connected to a three way tap managed by the patient (open-closed) at day3 and day4. Group 2 received at day1 and day2 the elastomeric pump and then the electronic pump. All patients continued at home with the elastomeric pump. Flexion-extension capacity of the elbow, daily consumption of ropivacaine 0,4%, and patients comfort were all evaluated. RESULTS: With the electronic pump, flexion-extension capacity is significantly better compared to elastomeric pump. During the use of the electronic pump, consumption of ropivacaina 0.4% was significantly higher in day2 compared to day1 (physiotherapy started day2); consumption in day3 and Day4 was significantly less compared to day2. All patients preferred the electronic pump for the first two days and then the elastomeric pump. CONCLUSION: PCRA quality is higher with ropivacaine 0,4% during the first phase of recovery. The elastomeric pump instead, insufficient in the first phase, is useful for analgesia at home. PMID- 11778106 TI - Spinal anesthesia in children: pro. AB - Spinal anaesthesia, first introduced in children at beginning of 20th century, offers adequate intraoperative anaesthetic conditions (analgesia and muscle relaxation). The technique is easy to perform even if lumbar puncture is more difficult when the children is smaller. It has not been observed haemodynamic modifications especially in patients under 5 year of age; duration of spinal anaesthesia is shorter if compared to adults and post dural puncture headache (PDPH) after spinal anaesthesia is as common in children as it is in adults, but was usually mild and very short lasting. PDPH has not been correlated with the type of spinal needle used. Hyperbaric solution of local anaesthetics like bupivacaine and tetracaine are preferable. The only adjuvant used for spinal anesthesia in children is morphine, which should be administered only in patients admitted to high dependency unit in the postoperative period. Spinal anaesthesia is indicated mainly in sub umbilical surgical procedures lasting no more than 90 minutes and particularly in the surgical treatment of former premature infants who present an higher risk with regional anaesthesia. PMID- 11778107 TI - [Caudal block in pediatrics]. AB - Caudal block is the single most popular regional anesthetic technique used in infants and children. A review of the literature concerning complications related to this technique reveals that it is safe and it has a low failure rate. Probably the incidence of complications of caudal block is 7/10.000, the lowest of all the central blocks. High success rates in performing caudals in children are achieved after a lower caseload than for other regional anesthetic procedures. The success rate in children under 7 years of age is 99%, but most failures occur in the oldest. Caudal anaesthesia can be used for anything surgical under the umbilicus and is an acceptable alternative to general or spinal anaesthesia in premature and high-risk infants, where a regional anaesthesia alone may be preferable. Caudal morphine has been used successfully for postoperative analgesia in children of all ages, including neonates after open-heart surgery. Possible complications of this technique are: local anesthetics overdose, vascular penetration and intravascular injection of local anesthetics, dural puncture and total spinal anaesthesia, intraosseous injection, infections, meningitis, respiratory depression (when morphine is used). Authors analyze all these complications and the safety rules for their prevention. PMID- 11778108 TI - [General anaesthesia for orthopaedic pediatric surgery]. AB - When there are no precise indications or contraindications, the choice between general anaesthesia and locoregional anaesthesia is not clear-cut, especially in paediatrics where there are not enough prospective studies about the safety and main complications with the two techniques. This study aims at providing some clarification concerning this problem by outlining the practice of anaesthetics in the Children's Orthopaedic Ward of Rizzoli Orthopaedic Institute which, for logistical reasons and based on past experience, was carried out by the exclusive use of general anaesthesia. The organizational aspects of pre- and post-operative management of the patients are described. In addition, the data of 836 general anaesthetics carried out in the year 2000 were recorded prospectively on a daily basis. The data included the characteristics of the patient, type of surgery, anaesthesiological methods, and intra- and postoperative complications (first 24 hours). No major complications occurred. There was a small incidence of minor complications (13,3%), which all resolved without sequelae. In the group of younger children, where the lowest number of adverse events were recorded (9,7%), halothane was prevalently used, analgesic opiates were excluded, and breathing was maintained spontaneously. The authors deem the results satisfactory with regards to safety and morbidity, and recommend that anaesthetists use the anaesthesiological methods with which they are more experienced and that are most compatible with the logistical and organisational conditions in which they must work. PMID- 11778109 TI - [Two in one block for carotid surgery]. AB - The choose of the best anaesthesia for carotid surgery is a very debated item: the locoregional techniques probably offer more hemodynamic stability and a direct neurologic monitoring, while general anaesthesia allows the complete control of airways and ventilation and reduces the global stress for the patient. This review analyzes the data of studies that compare general and locoregional anaesthesia. Among the latter, possibly elective techniques, the one described by Winnie combines an optimal analgesic efficacy with the lowest rate of adverse effects. A single bolus of a local anesthetic injected at a C4 level (apex of scalene muscles triangle) guarantees a complete block of the superficial and deep cervical plexuses. PMID- 11778110 TI - Regional anaesthesia in vascular surgery: a multidisciplinary approach to accelerate recovery and postoperative discharge. AB - A multimodal, rehabilitative, fast discharge approach to abdominal aortic surgery is analyzed. The approach was developed in two phases during the years 1997-2000: in the first phase (1997) patients had thoracic epidural anesthesia plus TIVA and analgesia. They had improvement of the classical surrogate outcomes and analgesia: pain relief, nasogastric tube withdrawal, mobilization, ileus, hospital length of stay were significantly (p< 0,01) improved when compared to a historical, standard management group (1996: general anesthesia or lumbar epidural anesthesia plus general anesthesia with gas). In the second phase we started a more aggressive perioperative approach based on thoracic epidural anesthesia plus general anesthesia with gas and spontaneous breathing and postoperative epidural analgesia, left subcostal minilaparotomy incisions, aggressive postoperative nursing and pain relief on the ward. Preliminary results on 44 patients show no mortality, low postoperative morbility (cardiac complications 2,2%, peripheral embolization 2,2%, no pulmonary complications), no ICU stay and fast hospital discharge (median: 3,5 days, range: 2-8 days) without complications. We conclude that preliminary data support the safety and the need for further improvement of a multimodal, aggressive rehabilitative approach in abdominal vascular surgery. PMID- 11778111 TI - [Sufentanil vs morphine combined with ropivacaine for thoracic epidural analgesia in major abdominal surgery]. AB - BACKGROUND: Pain, postoperative ileus, nausea, vomiting are the universal complications after major abdominal surgery. The aim of this study was to assess pain relief, side effects and recovery of gastrointestinal function during epidural analgesia with ropivacaine plus sufentanil and ropivacaine plus morphine after major abdominal surgery. METHODS: In this prospective study, sixty patients (median age 62+/-12 years) undergoing major abdominal surgery, after informed consent, were randomized into two groups, during a period of 3 months. Patients who were not considered suitable candidates for epidural anaesthesia were excluded. Epidural catheters were inserted at T8-T9 (upper abdominal surgery) or T9-T11 (lower abdominal surgery) and ropivacaine 0,5% 7-9 ml (upper abdominal surgery) or 10-12 ml (lower abdominal surgery) combined with sufentanil 30 mcg (group S, n=30) or with morphine 2 mg (group M, n=30) was injected. General anaesthesia was induced and a continuous epidural infusion of ropivacaine 0.5% 5 10 ml/h was begun. Postoperatively, continuous epidural administration of ropivacaine 0.2% plus sufentanil 0.5 mcg/ml (group S) or ropivacaine 0.2 plus morphine 0.02 mg/ml (group M) was continued. Data on the quality of analgesia, recovery of gastrointestinal function and all side effects were recorded for 48 hours. RESULTS: Incident and resting pain scores were not significantly different among group; although sufentanil provided better resting pain scores at 16th, 20th, 24th hours, and incident pain score at 24th hour. The incidence of nausea, vomiting and pruritus was more in morphine group (p<0,0001). Time to the first flatus was significantly shorter for patients in the sufentanil group (p<0,0001). The quality of pain relief assessed by the patients was rated as good in all patients. CONCLUSIONS: Continuous administration of epidural ropivacaine combined with sufentanil or with morphine resulted in good analgesia. Epidural analgesia with ropivacaine plus sufentanil provided the best balance of analgesia, side effects and recovery of gastrointestinal function. PMID- 11778112 TI - [Prehydratation and anaesthesia in obstetrics: state of the art]. AB - All epidural or spinal techniques using local anaesthetics causes some degree of sympathetic blockade resulting in peripheral vasodilatation and possibly hypotension or reduction in cardiac output. In the practical clinic, administration of fluids intravenously prior spinal and epidural anaesthesia is required to prevent maternal hypotension and fetal hypoxia. We evaluated in this review the efficacy of volume preloading on the incidence of hypotension after spinal or epidural anaesthesia for caesarean delivery. Randomized controlled trials investigating volume preloading before the initiation of obstetric anaesthesia were sought by using MEDLINE (1966-2001). The primary outcome was the incidence of hypotension. Secondary outcomes included: ephedrine use, Apgar scores, umbilical cord pH values, and maternal nausea and vomiting. Crystalloid preload was inconsistent in preventing hypotension, whereas colloid appeared to be effective in all studies. A colloid solution, such as hydro-xyethyl starch (HES) might be preferable considering the capacity to stay intravasculary for a longer period. Few differences in fetal outcomes or maternal nausea and vomiting were reported. Increasing central blood volume by using colloid decreases the incidence of hypotension before loco-regional anaesthesia for cesarean delivery. Implications. We performed a review to determine whether fluid loading reduced the incidence of low blood pressure after spinal or epidural anaesthesia for caesarean delivery. Although no technique totally eliminates the occurrence of hypotension, colloid administration (starch or gelatin containing fluids) was the most effective. PMID- 11778113 TI - [Spinal or epidural anaesthesia for caesarean section? Compared opinions]. AB - Regional anaesthesia during caesarean section reduces mortality directly related to anaesthesia. Epidural anaesthesia is a good choice when an epidural anaesthesia was performed during labor. General anaesthesia is recommended only for emergency caesarean section and when regional anaesthesia is contraindicated. The Authors describe the reasons for choicing an epidural or a spinal block. Main points supporting spinal block are facility in performing, quickness of the achievement of the block and a good quality of sensorial and motor block. On the other side epidural anaesthesia makes the anaesthesist able to titrate with exactness the level of sensorial block and offers a good postoperative analgesia. Because of the introduction of atraumatic needles PPDH has drammatically decreased: accidental PPDH takes place in a small but ingrained percentage. Recently spinal block has been described as a reliable choice even in preeclampsia and in pregnancy hypertension. Epidural opiates have a lower incidence of maddening side effects compared with spinal opiates and allow better maternal satisfaction as regard postoperative analgesia. In accordance with ASA guidelines there are no decisive reasons in order to choice spinal or epidural block: actually literature is unable to give a definitive suggestion about complications and advantages. The choice would be take place weighing up maternal wishes, fetal factors (elective versus urgent caesarean section) and the preferences of the anesthesiologist. PMID- 11778114 TI - [Complications related to epidural catheter in caesarean delivery]. AB - A review of complications related to epidural catheters in caesarean delivery is presented. Catheters for prolongation of nerve blocks were first used in 1940s. Thereafter, there has been steady development in the design and plastic material technology of the different catheters. In the last decade the regional anaesthesia for caesarean section became very popular, as well as continuous increase in the use of epidural catheters. The anatomical changes of pregnancy like marked distension of the epidural veins resulted in increased risk of the complications due to the epidural catheter placement. It is likely that permanent neurologic sequelae due to regional anaesthesia in obstetrics almost never occur, while minor self-limiting complications do occur. The possible complications of epidural catheter techniques are: trauma, malposition and migration of the catheter, knotting and breaking, radiculopathy, dural puncture, subdural injection, abscess and infection, haematoma and wrong solution injection. Most of the malpositions of the epidural catheter can be avoided by a careful technique, advancing the catheter with no forceful movement and not more than 3 to 4 cm into epidural space. Broken parts of the catheters should be left as a rule within the spinal space. Test dose should be always done for continuous epidural anaesthesia. Early diagnosis and prompt appropriate treatment will usually lead to complete resolution of the neurological deficit even in cases of epidural haematoma or abscess. PMID- 11778115 TI - Pain free hospital: organisation aspects. AB - The rational approach to acute pain management is to use the highest quality evidence available. Acute pain management is more than a collection of interventions. It is a package of care that needs to be examined as a whole as well as in its parts. In the context of acute pain management, this comes from systematic reviews of valid randomised trials. We still have to adapt to the circumstances of the individual, but our policies will be more discerning. Acute pain is not confined to postoperative wards but it is a problem in many clinical settings. Educational programs for allied health professionals are equally important because they play the key role in the management of acute pain. Accreditation and educational programs in individual institutions would enable the nurses to identify their learning needs, to acquire appropriate knowledge and skills to ensure that they are adequately prepared for the responsibilities involved in pain management. The key of successful pain management is education, not new drugs or high-tech delivery systems. Existing tools can do the job if doctors and nurses are educated, both to dispel the myths and misconceptions and to take responsibility for providing pain control. It is much easier to dispel myths when you have the evidence. In 1846, the first anaesthetic provided pain free surgery - 150 years later patients should not have to endure unrelieved pain anywhere in the hospital. PMID- 11778116 TI - [Quality of the postoperative course and patients' satisfaction produced by a system of postoperative pain control: postoperative clinical evidence that influences the quality of the postoperative course]. AB - Acute pain treatment after surgery or trauma, when inadequate, contributes to increased morbidity and prolonged in hospital stay. Acute postoperative pain management can be realised by application of treatment protocols and the regular assessment of the patients clinical conditions. The aim of the ACUTE PAIN SERVICE (APS) is to plan postoperative treatment. According to our experience, besides providing assistance, the APS elaborates results and intervenes through regular audits to improve quality. This system is further enriched through collection of information obtained through an anonymous questionnaire compiled by the patients about forty eight hours after surgery. The questions are expressed such to outline a judgement about patients' satisfaction towards the services supplied by the agency. OBJECTIVE: Evaluation of effectiveness of pain treatment and level of postoperative wellbeing through continuous observation of the patient. METHODS: a retrospective study on about 4400 consecutive patients arriving at the APS in the last 2 years of activity, who have been evaluated at fixed moments using various indicators (VAS at rest/activity, PONV and other discomforts). RESULTS: Follow-up of the patients showed that: - pain relief, when reached, does not conform well being; - for certain symptoms of discomfort, specific protocols are necessary; - there are correlations between type of surgery, type of anaesthesia and discomfort, which may be reducible through the right attitude in behaviour and therapy; - antalgic therapy itself can cause several side-effects. The solution of the discomfort problem gets close to the concept of perioperative medicine in which APS action goes beyond pain, towards a more complete pain management. PMID- 11778117 TI - [Systemic analgesia after peripheral block]. AB - Over the past few years, increasing emphasis has been placed on the need to improve the management of acute pain. Despite a growing trend in acute pain management, many difficulties are still present for the treatment of postoperative pain. Loco-regional techniques together with an effective pain management should accelerate rehabilitation, decrease risk of postoperative complications and speed return to normal activities. A multimodal approach should be used for a reduction of pharmacological side effects, improving pain reduction. The association between NSAIDs and opioids permits reduction of full dose opioids with better pain relief and less side effects. If NSAIDs are contraindicated, acetaminophen is an alternative, though considered by someone to be an NSAID It's action is believed to result from inhibition of prostaglandin synthesis within the central nervous system. It doesn't cause gastrointestinal ulceration or bleeding, but we have to note that large amounts may lead to hepatic necrosis. Newer NSAIDs (COX-2 inhibitors), affect mainly COX-2, and appear to be associated with less adverse effect. Rofecoxib showed a reduction of morphine consuming after spinal fusion and has been admitted by FDA for the treatment of post operative pain. Newer methods of pain relief, as patient controlled analgesia (PCA), can provide excellent and safe pain relief. When high tech options such as PCA are used, patients need a management by an anesthesiologist-based acute pain service (APS), allowing a better pain relief with less side effects compared to patients supervised by less experienced medical staff. PMID- 11778118 TI - Treating postoperative pain improves outcome. AB - Recent surveys show that many patients still receive inadequate post-surgical analgesia, this problem is international in character. Analgesia techniques like patient-controlled analgesia (PCA) and spinal opioids alone or in combination with local anaesthetics provide superior pain relief compared to intermittent i.m. injections of opioids. Patient satisfaction with these techniques is high; however, reduced pain and suffering or high patient satisfaction is not considered sufficient in this age of diminished health care budgets. There is no overwhelming evidence that effective postoperative pain relief assures good postoperative outcome. Most studies lack sufficient statistical power to detect clinically significant differences. A meta-analysis showed higher patient satisfaction with i.v. PCA compared to i.m. opioid injection. Although PCA still is the standard of care there's little rational or scientific evidence that i.v. PCA improves outcome. A meta-analysis of randomized, controlled trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after various procedures has shown that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity. None of the other analgesic techniques had a significant impact on pulmonary outcome. There are few outcome studies with peripheral nerve blocks. Evidence that peripheral nerve blocks are better than PCA and safer than epidural increases. One reason why improved outcome is difficult to demonstrate is that pain management strategies are not integrated with overall perioperative care and postoperative rehabilitation of the patient. The importance of a good APS in developing cost effective, evidence-based pain treatment strategies for different surgical procedures should not be underestimated. PMID- 11778119 TI - Sufentanil: an overview of its use for acute pain management. AB - The knowledge of pharmacodynamics and pharmacokinetics of new opioid drugs is necessary so that anaesthesiologists can choose which one to use, considering the patient's pathophysiology, the surgical procedure, and the dose required to obtain the desired effect. Aim of this review was to evaluate relevant trials on perioperative sufentanil in order to design an optimal strategy for administration. METHODS: Randomised controlled trials on perioperative sufentanil analgesia were identified by Medline research, Embase, Biosis, Scisearch and references mentioned in relevant reviews were hand searched from 1988 to June 2001. RESULTS: Twenty-four trials were considered eligible; they were divided according to the use of sufentanil in abdominal surgery, paediatric surgery and other types of surgery (orthopaedic, maxillo-facial, thoracotomy, lithotripsy, etc.). It was possible to compare the use of iv and epidural sufentanil, in iv PCA and PCEA, in continuous infusion, alone or in combination with local anaesthetics (various concentrations of ropivacaine, bupivacaine), with clonidine, adrenaline and ketamine. CONCLUSIONS: Efficacy of sufentanil in perioperative epidural or intravenous analgesia resulted the same or better than other drugs used commonly despite context-sensible half-life advantages. Its association with local anaesthetics or adjuvant drugs prolongs its action and sometimes decreases the side effects. From the examined trials results that sufentanil can be used at very low doses and its association with local anaesthetics, clonidine, ketamine, and adrenaline by epidural, intravenous or intrathecal route for perioperative analgesia (intra and postoperative) and by various types of administration (PCA, PCEA, fixed intervals doses, continuous infusion, etc.). PMID- 11778120 TI - [Orthopaedic day surgery in Emilia-Romagna]. AB - It is well known that the organizational model of day surgery, concerning surgical problems defined by the literature as minor, has the aim of optimising the use of hospital resources and facilitating patients and their families, from a psychological and social point of view, by reducing hospitalisation time and the associated complications, and ensuring the same efficacy and more appropriateness of treatment. This study is firstly aimed at analysing the impact that the healthcare policy of the Emilia Romagna Region has had on the development of day surgery practice. Secondly, it compares the patients treated in orthopaedic day surgery in the hospitals of Bologna, Modena, Ferrara, Parma, Reggio Emilia, Maggiore hospital of Bologna and Rizzoli Orthopaedic Institute of Bologna (II.OO.R). In the period 1997-2000 there was a marked increase in the number of operations carried out in day surgery in all of the above-mentioned hospitals. Also in the unispecialistic orthopaedic hospital there was a surprising increase in the percentage of operations carried out in day surgery with respect to the total number of operations performed. The aim of the Rizzoli Orthopaedic Institute and the Emilia Romagna Region is to further implement this form of healthcare, contextually potentiating the appropriateness of hospital admission and avoiding, when not necessary, other forms of healthcare. PMID- 11778121 TI - [Orthopaedic one day surgery: anaesthesiologic techniques used and intra- and postoperative complications]. AB - OBJECTIVE: Optimize patient management in one day surgery (ODS) by an observative study regarding one day orthopaedic surgery, assessing kind and quantity of intra and postoperative complications, need for prolonged postoperative assistance postponing discharge, recovery in other hospitals, patients satisfaction index. METHODS: From september 1999 until december 2000 we distributed a questionnaire 1286 consecutive patients. The patients were ASA I (80,7%), ASA II (17%) and ASA III (2,3%). We evaluated intra- and postoperative complications considering type of surgery and anaesthesiologic technique; need and reason for medical consulting; if consulting took place in other institutes. Patients judgement regarding medical and nursing assistance during in hospital stay was assessed. RESULTS: Main surgical procedures: arthroscopy (44,6%), internal fixation removal (21,3%), neurolysis (9,5%), cysts/tumours/nodules removal (7,5%), foot surgery (8,0%). Used anaesthesiologic techniques: neural block (65,6%), plexus block (15,1%), general (12,5%), spinal (4,8%) and local anaesthesia (1,9%). An intraoperative complication (convulsion) was reported twice. Postoperative complications: pain (3,6%) most frequent in foot surgery (5,2%), nausea (0,2%), fever (0,7%), haematoma (0,5%). 5 delayed discharges (beyond 24h) were reported, for surgical reasons. In 5 cases another institute was visited. There were no deads. CONCLUSIONS: The percentage of not planned recoveries (0,1%) is an indication of frequency of major complications. Satisfaction index of patients was high (96%). Kind of surgical procedure and anaesthesiologic technique, considering the minimal intra- and postoperative complications, are adjusted to the ODS regime. Reinforcing analgesic protocols in foot surgery though are necessary. According to our opinion the peripheral block is preferable in orthopaedic ODS. PMID- 11778122 TI - Regional anesthesia for outpatient orthopedic surgery. AB - The constant search for increased efficiency and reduction of hospital length of stay has led to an increase number of major orthopedic procedures performed as outpatients and the increase in the associated intensity and duration of acute postoperative pain. Although, it is well established that single peripheral blocks provide adequate anesthesia and excellent immediate postoperative analgesia in patients undergoing minor ambulatory orthopedic surgery, the postoperative acute pain benefit is limited to less than 24 hours. However, many patients required over 24 hours of intensive postoperative analgesia. Furthermore the need for immediate postoperative physical therapy in orthopedics dictates that local anesthetics be chosen on the basis of their safety and ability to produce preferential sensory blocks. As early as 1946, Ansbro proposed the use of continuous nerve blocks to prolong the duration of analgesia of nerve block technique during anesthesia. Continuous nerve blocks have also been used for the acute postoperative pain control of patients undergoing major orthopedic surgery as in-patients. This technique has been proven to be safe and effective in controlling acute postoperative pain and improve functional outcome. The recent introduction of safer local anesthetics producing preferential sensory blocks along with the development of ambulatory pumps has allow to extend the use of these continuous block techniques to ambulatory patients. Recent development also included the use of cox2 inhibitors along with cold maximize postoperative analgesia. This multimodal approach has been proven to be safe and efficacious as much for resting pain than pain associated with exercise. PMID- 11778123 TI - [Severe and prolonged post-dural puncture headache: from pathological basis to therapeutic role and correct timing for epidural blood patch]. AB - Believed to be due to unbalance between cerebrospinal fluid (CSF) production rate and its loss through the spinal dural puncture hole, post-dural puncture headache (PDPH) is often considered as a physiological syndrome, usually reversible without pathological sequelae after dural hole's closure. The clinical case here presented (incapacitating headache associated with diagnostic dural puncture in a leukaemic young female patient who underwent bone marrow transplantation) shows potentially fatal pathological sequelae following prolonged headache (untreated, due to the severe postransplant immunodeficiency and coagulopathy). The observed RMI lesions suggest interesting conclusions about the clinical indications and correct timing of autologous epidural blood patch (EBP). We also suggest the ways to preventing rebound intracranial hypertension following autologous epidural blood patch in patients suffering from incapacitating and prolonged headache. PMID- 11778125 TI - Premedication, preparation, and surveillance. AB - The vigorous debate over whom to sedate, when to sedate, and how to sedate shows no sign of running out of steam. There is a general consensus that patients should be more involved in the decision-making process for the sedation "menu". A move away from the take-it-or-leave-it attitude of all or nothing to an "a la carte" choice is to be encouraged. A new textbook and several further guidelines have appeared. The particular problems associated with sedating the elderly are briefly presented. The pros and cons of using local pharyngeal anaesthesia are discussed. Enthusiasm for the use of intravenous propofol is gathering momentum, despite continuing worries about its safety in the hands of the nonanaesthetist. For many endoscopists, the combination of a benzodiazepine plus (or minus) an opioid with which they are most familiar is still the best compromise in terms of efficacy, cost, and safety. Fatal drug-induced cardiopulmonary complications continue to occur, despite a general trend toward using smaller doses of sedation than we did 5 - 10 years ago. Monitoring techniques that are at present considered as research tools may one day become commonplace. These include: the use of an electroencephalography parameter known as bispectral analysis; transcutaneous CO(2) measurement; and a modified continuous capnographic waveform trace to monitor ventilatory effort. Bispectral analysis may be of use in monitoring central nervous system depression and helping to distinguish between conscious sedation and deep sedation. If the measurement of CO(2) levels, either transcutaneously or in breath samples, was as easy and inexpensive as measuring SpO(2) with a pulse oximeter, then undoubtedly such technology would enhance the early detection of sedative-induced hypoventilation and apnoea. Further evidence regarding droperidol's possible role in conscious sedation is presented. Pain during colonoscopy remains a problem, and the possible role for intraluminal injection of peppermint oil, as well as the value of variable-stiffness colonoscopes, in reducing the need for intravenous sedation is discussed. Case reports of hyponatraemic encephalopathy and hypocalcaemic tetany as complications of oral bowel preparation are presented, as is the challenge associated with adequate bowel preparation in diabetic patients. PMID- 11778127 TI - Endoscopic ultrasonography. AB - Over the past two decades, endoscopic ultrasonography (EUS) has undergone a transition from being a novel imaging technique to a clinical diagnostic test that is necessary for the optimal management of gastrointestinal diseases. EUS has established itself as an important diagnostic modality, mainly for the detection and staging of gastrointestinal cancers. As EUS has become more widespread, research has gradually shifted towards studies that explore the effect of EUS on patient management and outcome. These outcome studies have examined the primary clinical applications of EUS, such as esophageal, gastric, pancreatic, and colorectal cancer staging, as well as the role of EUS in the diagnosis of inflammatory pancreatic diseases. Widespread use of EUS has recently led to studies that examine complications associated with the performance of the procedure. Endosonographers have continued efforts to define a clinical role for EUS in other gastrointestinal diseases, such as portal hypertension. EUS-guided fine-needle aspiration (FNA) is continuing to develop into a powerful diagnostic tool for the management of lung cancer and other mediastinal diseases. New applications for EUS-FNA are also emerging. Finally, investigators are continuing to explore the remaining frontier of EUS-guided therapy. PMID- 11778126 TI - Small-bowel endoscopy. AB - During the last year, promising results with the first clinical applications of capsule endoscopy have been reported; this is a new, revolutionary diagnostic method for endoscopic study of the small bowel. The method has chiefly been used in patients with obscure gastrointestinal bleeding, and in some cases has allowed additional diagnoses to be made in comparison with push enteroscopy, with a positive influence on patient management. New therapeutic possibilities have also been developed in push enteroscopy, emphasizing the role of this technique as an essential component of gastrointestinal endoscopy. Important innovations in enteroscopy technique have been described, aimed at increasing the depth of examination, and these will probably make it possible to extend endoscopic treatments to include the entire small bowel. Finally, numerous articles are still being published concerning intraoperative enteroscopy. It is to be hoped that, in future, the use of this invasive procedure will be based on data acquired by capsule endoscopy. PMID- 11778128 TI - Diagnostic ERCP. PMID- 11778129 TI - Therapeutic biliary endoscopy. AB - An analysis of the recent medical literature on therapeutic biliary endoscopy shows that the new millennium has already brought several significant developments. However, although advances continue rapidly, several new questions have also arisen, paving the way for further research. Several studies during the last year have also focused attention on cost-effectiveness. PMID- 11778130 TI - Therapeutic pancreatic endoscopy. AB - Pharmacological treatment and/or temporary pancreatic stenting can reduce the risk of pancreatitis after endoscopic retrograde cholangiopancreatography. Potential candidates are patients who are at high risk for this complication. Extensive diagnostic work-up is needed for patients with acute recurrent pancreatitis before treatment can be planned. Endoscopic pancreatic sphincterotomy or temporary stenting, or both, appear to be beneficial in idiopathic recurrent pancreatitis. Short-term stent placement in the dorsal duct, with or without papillotomy of the minor papilla, is a promising approach in patients with symptomatic pancreas divisum, particularly if it is associated with acute recurrent pancreatitis. Endoscopic treatment of chronic obstructive pancreatitis is technically effective and safe, but the indication remains controversial, mainly due to a lack of controlled trials. Endoscopic transmural drainage of pancreatic pseudocysts or abscesses is very effective, and should be considered as a primary approach in symptomatic patients. The endoscopic ultrasonography-guided technique extends the options for obtaining access to fluid collections in difficult locations, and may further increase the safety of the procedure. Many of these procedures are technically demanding, and should be restricted to high-volume centers; there is a continuing need for further evaluation and comparison with alternative strategies. PMID- 11778131 TI - Inflammatory bowel disease. AB - This article reviews a selection of 50 papers on inflammatory bowel disease published between April 2000 and June 2001. The new information summarized here includes: the discovery of the association of the NOD2 gene with Crohn's disease; the role of bacteria and the modulating effects of probiotics; the inverse association of appendectomy and ulcerative colitis; progress in imaging based on magnetic resonance imaging and leukocyte scintigraphy; assessment of the value of anti-Saccharomyces cerevisiae antibodies in the screening of inflammatory bowel disease and differentiation between ulcerative colitis and Crohn's disease; and risk factors and management of dysplasia and cancer. This article does not review all therapeutic aspects, but focuses on smoking cessation; anti-tumor necrosis factor antibody treatments; the usefulness of measuring erythrocyte 6-thioguanine metabolite levels to optimize purine analogue therapy; strictureplasty; and the long-term results of ileoanal anastomosis. PMID- 11778132 TI - Colon polyps and cancer. AB - The superiority of colonoscopy to double-contrast barium enema in detecting neoplasia was finally demonstrated in 2000, but colonoscopic surveillance programs are still based on short-term observations and are mostly inadequate, despite the prospective design of the trials. The evaluation of the diagnostic accuracy of virtual colonoscopy is in progress, but its appropriate place in clinical gastroenterology has not yet been defined. There is now solid evidence that screening with fecal occult blood testing (FOBT) not only reduces the mortality from colorectal cancer, but also that the incidence is substantially reduced after removal of the precursor lesions. Feasibility studies for population screening are ongoing. A once-only sigmoidoscopy will probably not be an optimal method of screening, but may be added to a program with FOBT. Molecular stool screening is attractive, but still experimental. Colonoscopy is not attractive as an initial screening instrument, despite its high diagnostic accuracy, and should only be used for screening high-risk individuals. Genetic methods are playing an increasing role in defining prognostic markers for intestinal neoplasia, and it is recommended that information services should be established for the public. Chemopreventive studies have revealed that dietary fiber supplementation may not reduce the risk of adenomas; the opposite seems to be true for aspirin and non-aspirin NSAIDs, which are active in the early phase of carcinogenesis. New techniques for optimizing diagnostic and therapeutic colonoscopy have been introduced. PMID- 11778133 TI - Actual behaviour of N-butyl-2-cyanoacrylate (histoacryl) in a blood vessel: a model of the varix. AB - BACKGROUND AND STUDY AIMS: Though many gastric varices are treated endoscopically with n-butyl-2-cyanoacrylate, its behavior in varices is not known precisely. MATERIALS AND METHODS: We created a varix model. A volume of 0.7 ml or 1.4 ml of 71.4 % n-butyl-2-cyanoacrylate, a tissue adhesive, was injected into vinyl tubes of 0.4, 0.6, 0.9, and 1.2 cm in diameter, which were filled with still blood or flowing blood. The tissue adhesive was also injected into the inferior vena cava or femoral vein of dogs. RESULTS: N-butyl-2-cyanoacrylate was similarly polymerized in the vinyl tubes and the animal veins. A volume of 0.7 ml of the tissue adhesive could block all tubes up to 0.6 cm in diameter. A double quantity of the tissue adhesive could block tubes 0.9 and 1.2 cm in diameter, with flow velocities up to 10 cm/s and up to 5 cm/s, respectively. Some polymer masses were fragmented. CONCLUSIONS: One rapid shot of the tissue adhesive can block a vessel 0.6 cm or less in diameter with fast flow velocity, and a vessel up to 1.2 cm in diameter with slow flow velocity. Fast blood flows in a larger diameter vessel and slow injection of the tissue adhesive may result in fragmentation. This model of the varix was useful for assessing the effect of tissue adhesive used to treat gastric varices. PMID- 11778134 TI - The effect of midazolam on the normal sphincter of Oddi: a controlled study. AB - BACKGROUND AND STUDY AIMS: Midazolam HCl (Versed) is often used for intravenous conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and is increasingly used in endoscopic sphincter of Oddi (SO) manometry. The effect of medications on SO motility should be fully characterized if they are to be used during SO manometry. There has been controversy as to whether midazolam influences SO motility. The aim of this study was to determine the effect of midazolam on the normal SO. PATIENTS AND METHODS: The study population consisted of 60 patients presenting with recurrent abdominal pain who were found to have SO basal pressure of less than 40 mmHg on SO manometry. ERCP was performed in the standard fashion using a pneumohydraulic capillary perfused triple-lumen catheter system in a stationary pull-through method from the pancreatic and common bile ducts. In the test group 30 patients received 2 mg midazolam intravenously while the 30 patients in the control group received intravenous saline. SO manometry was performed, with recording of the basal pressure, phasic pressure, phasic amplitude, phasic frequency and ductal pressure before and 3 min after the intravenous infusion. The changes in basal, phasic and duct pressure as well as phasic frequency before and after the administration of saline and midazolam were compared. RESULTS: Midazolam causes a small but statistically significant reduction in basal and peak SO pressure (4 and 19 mmHg respectively), compared with saline. Diagnostic concordance (normal vs. abnormal) between the basal sphincter pressure before and after midazolam was seen in 100 % of patients. Midazolam does not significantly affect phasic amplitude, phasic frequency or duct pressure. CONCLUSIONS: Midazolam does not have a clinically significant influence on the accuracy of SO manometry in identifying normal sphincteric motility. PMID- 11778135 TI - Use of endoscopic ultrasound-guided injection in endoscopic resection of solid submucosal tumors. AB - AIMS: Submucosal tumor (SMT) is a common disease. We used endoscopic ultrasound (EUS)-guided puncture to inject saline before resection of SMTs, and evaluated the usefulness of this method. PATIENTS AND METHODS: We selected 16 symptomatic patients with solid SMTs in the upper gastrointestinal tract, confirmed by endoscopy and EUS. We first used EUS-guided puncture to inject saline to separate the submucosal lesions from the deeper normal tissues. Lesions in the muscularis mucosa and submucosa were then removed directly by snare cauterization. Lesions in the muscularis propria were treated by means of a two-step approach: first, we incised the superficial tissue of the tumors using an electrosurgical needle, and second, we enucleated SMTs as much as possible by tightening the snare around them and creating pseudo-stalks. After snare excision of SMTs, the cleavages of the superficial tissues were closed using metal clips. RESULTS: Among the 16 patients, one lesion was in the muscularis mucosa, six were in the submucosa, and nine were in muscularis propria. All the lesions were resected thoroughly. No perforation occurred nor had any recurrences been observed at follow-up of 12 - 17 months. CONCLUSIONS: EUS-guided puncture to inject saline before resection is a safe and accurate procedure in the treatment of submucosal tumors. PMID- 11778136 TI - Successful repair of a damaged duodenal stent by cutting stent wires and placement of a second stent. AB - Duodenal stenting has been gradually established in recent years because it is less invasive than standard surgical procedures and produces a rapid therapeutic response. For palliation of both duodenal and biliary stenoses, double stenting may be performed. Duodenal stents offer a great advantage in allowing endoscopic retrograde cholangiopancreatography (ERCP) without the need for balloon dilation. When biliary stent dysfunction occurs, the patient undergoes diagnostic and/or therapeutic ERCP across the duodenal stent. We encountered a duodenal stent fracture in a patient who required repeated ERCPs for stent dysfunction. Duodenal stent fractures have not previously been reported. The damaged stent was successfully repaired by using a cutting wire filament and placing another duodenal stent coaxially with the first. Clinicians should be aware of the possibility of stent fracture following endoscopic procedures, such as an ERCP, that require passage through the stent. The procedure described in this report would be of significant benefit if a gastrointestinal stent is fractured and occluded by a broken part. PMID- 11778137 TI - Thermal coagulation for nonvariceal bleeding. PMID- 11778138 TI - Hemopericardium caused by ingested safety pin. PMID- 11778139 TI - Three-dimensional ultrasonography, virtual coloscopy and endorectal magnetic resonance imaging in the diagnosis of complicated inflammatory bowel disease. PMID- 11778140 TI - Current scientific programmes in German neurosciences: supported by official sponsors. PMID- 11778141 TI - Death attributed to methadone. AB - Besides its other effects, MMT (methadone maintenance treatment) reduces the high mortality of intravenous heroin addicts to about 30% of controls. On the other hand, deaths of patients and non-patients have been attributed to methadone. Here, we will report on the major reasons for deaths attributed to methadone and discuss suggestions for their prevention. 69% of deaths attributed to methadone occurred in subjects not on MMT at the time of their death. 51% of deaths attributed to methadone in subjects in MMT occurred during the dose-finding period of MMT. Further apparent risk situations are methadone intake in addition to that received for MMT, discharge from prison and intravenous injection of methadone. Intake of methadone in non-patients is almost entirely due to abuse of diverted take-home methadone. Not giving methadone as take-home should reduce methadone deaths most effectively. Replacing take-home methadone by substances acting longer than one day, such as LAAM (levacetylmethadol) or buprenorphine, should also be effective. Restriction of take-home prescriptions to substances with a slow onset of action, such as LAAM, or to partial agonists with an extended safety margin such as buprenorphine should be partly effective. Meticulous evaluation of substance history, slow dose increases and strict supervision of the patient by experienced personal should prevent methadone overdose during the dose-finding period. Discharge from prison closely corresponds to this situation; informing addicts shortly before discharge and psychosocial help during the first months out of prison may reduce this risk. Naloxone as an adjunct to oral agonist preparations should effectively prevent high-risk intravenous injection, for example of methadone syrup. This has been the case with tilidine plus naloxone in Germany. Reducing deaths attributable to methadone increases the net benefit of MMT. Also, reducing deaths attributable to methadone avoids decreases in the public acceptance of MMT. PMID- 11778142 TI - Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration. AB - In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity. PMID- 11778143 TI - Suppression of conditioned fear by administration of CCKB receptor antisense oligodeoxynucleotide into the lateral ventricle. AB - We investigated the role of CCK in the development of anxiety by determining whether CCKB receptor antisense suppressed intracellular Ca(2+) concentration in vitro or suppressed conditioned fear stress in vivo. First, for the in vitro studies, we used rat pituitary tumor GH3 cells since these cells have CCKB receptors. GH3 cells were stimulated by 10 microM CCK-4; intracellular Ca(2+) concentration was measured. The CCKB receptor antisense at 1 or 10 microM reduced the subsequent response to 10 microM CCK-4 in a time-dependent manner. Second, for the in vivo studies, the CCKB receptor antisense, sense, random sense, or saline was infused at a constant rate for 6 days into rat lateral ventricles via mini-osmotic pumps. Individual rats were then subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. Twenty-four hours later, the rat was again placed in the chamber and observed for 5 min without shocks. This study showed that CCKB receptor antisense significantly suppressed intracellular Ca(2+) concentration in GH3 cells and significantly reduced freezing behavior in rats, indicating that the CCKB receptor plays an important role in anxiety. PMID- 11778144 TI - Cytochrome P450 2D6 genotyping and association with tardive dyskinesia in Chinese schizophrenic patients. AB - BACKGROUND: The discovery of Cytochrome P450 2D6 (CYP 2D6) polymorphism is implicated in individual differences in drug metabolism rate. Mutation with defective alleles is associated with reduced metabolism of many anti-psychotic drugs metabolized by CYP 2D6. This may contribute to the development of tardive dyskinesia (TD) in patients with prolonged exposure to anti-psychotic drugs. METHODS: In this controlled study, the genotype of CYP 2D6*10 alleles, movement disorders and clinical characteristics in 38 Chinese schizophrenic patients with TD were compared with 38 age- and sex-matched schizophrenia patients without TD. RESULTS: There was no significant correlation between CYP 2D6*10 genotypes and TD in men. However, a significant increase in the frequency of CYP 2D6*10 allele was found in female patients with TD. CONCLUSIONS: The sex differences in CYP 2D6 genotyping and vulnerability to develop TD suggest that a biological predisposition that affects pharmacokinetics may be more significant in women, whereas other factors may be more important in men. PMID- 11778145 TI - Oxcarbazepine in affective and schizoaffective disorders. AB - Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic value in affective and schizoaffective disorders had been documented in several clinical trials. As the authorities in several countries registered newer anticonvulsants with fewer side effects, their therapeutic value in psychiatric disorders was studied. Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine (OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug interactions compared to carbamazepine and other anticonvulsants. Therefore, the value of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated. We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects of OCBZ in the treatment of patients with affective and schizoaffective disorders. According to the literature, OCBZ is regarded as effective in acute mania and appears to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does not interact substantially with the cytochrome P450 enzyme system, co-administration with neuroleptics or antidepressants appears to be well tolerated in affective disorders. However, despite promising effects of OCBZ, few clinical studies have been published in the last 15 years. We conclude that further studies should validate the efficacy of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as well as limitations for this psychotropic compound. PMID- 11778146 TI - Favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics: an MRSI study. AB - In the present study, we evaluated 23 chronic schizophrenic patients under stable clinical conditions to determine the association between neuronal viability, as measured by in vivo(1)H magnetic resonance spectroscopic imaging (MRSI), and antipsychotic drug effects in the anterior cingulate cortex. Careful screening of the medication history showed that 11 of these patients had been treated with traditional neuroleptics only, while the others had switched to atypical antipsychotics due to non-response to traditional drugs. The group of patients receiving typical neuroleptic medication showed a mean NAA that was lower than in the group of patients receiving atypical antipsychotic drugs. Removing the duration of illness effect indicated a significant correlation between the NAA signal in the anterior cingulate gyrus and time on atypical drugs in patients under long-term atypical antipsychotic treatment. In contrast, patients with traditional medication revealed progressive decrease in the NAA level. These results suggest a favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics. PMID- 11778147 TI - Treatment of pathological crying with citalopram. AB - Pathological laughing and/or crying may occur as a concomitant symptom of various diseases of the central nervous system. No known anatomical basis for any of these disorders exists at present. However, references to a disturbance in central serotoninergic neurotransmission have become frequent in the literature, implicating this as an important etiological factor. In the present communication three cases of successful treatment of pathological crying using the SSRI citalopram are reported. Besides the response of pathological crying in cerebral ischemia to SSRIs, which has already been described in earlier publications, this is the first report on the successful administration of citalopram for treating pathological crying in Parkinson's disease. Onset of response was very rapid in all cases. PMID- 11778148 TI - Asymptomatic bradycardia associated with amisulpride. AB - Well-known adverse effects of amisulpride include nausea, insomnia or tiredness, gastrointestinal, extrapyramidal and endocrine symptoms. Cardiac disorders, however, appear to be an extremely rare complication of the drug. Only a few case reports on this complication have been published so far, which deal with QT prolongation, hypotension, hypertension and palpitations. Bradycardia has not yet been mentioned. Here, we will report on a case of asymptomatic bradycardia that developed subsequent to therapeutic doses of amisulpride in a 25-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient had been rehospitalized for an acute exacerbation of the psychosis. When the patient failed to respond at the beginning of hospitalization, the treatment was changed from clozapine to amisulpride. After a complete switchover to amisulpride, the patient's ECG showed sinus bradycardia and QT prolongation. When the daily dose of amisulpride was reduced from 800 mg/d to 600 mg/d, the patient's ECG quickly normalized (including blood pressure and pulse rate) within a few days. The patient did not report any cardiovascular-related complaints. Since the cardiovascular-specific diagnostics did not yield any indicative results, bradycardia may be a rare complication of amisulpride treatment. PMID- 11778149 TI - Neuroleptic-induced pseudo-catatonia. PMID- 11778150 TI - Colonic fermentation as affected by antibiotics and acidic pH: Application of an in vitro model. AB - Antimicrobial substances such as vancomycin or metronidazole suppress normal gut flora, thereby preventing physiological fermentation of colonic substrates that may promote mucosal inflammation. This study was designed to establish an in vitro model of microbial metabolism in the colon under control and disturbed conditions (acidic pH) to investigate specific effects of vancomycin and metronidazole on the production of short chain fatty acids (SCFA), which play a pivotal role in maintaining homeostasis in the colon. The experiments were carried out with the colon simulation technique (Cositec) representing an in vitro model for the semi-continuous incubation of defined colon contents. Inocula and fermentable substrates were sampled from cecal contents of fistulated pigs. Disturbed microbial metabolism was generated by reduction of pH in the fermentation vessels from 6.7 to 5.8 and 5.1. In general, application of either vancomycin or metronidazole resulted in a significant decrease of SCFA production rates indicating substantial disturbance of the homeostasis of microbial metabolism. With low doses of vancomycin acetate and butyrate production rates were reduced and with high doses of the antibiotic propionate production was inhibited to a greater extent. Treatment with metronidazole inhibited butyrate production almost completely. Similarly, low pH caused a reduction in total SCFA production, which was mainly due to respective decrease of acetate synthesis. Metronidazole effects were not consistently changed at low pH. The Cositec system provides an excellent facility to test the effects of different antibiotics under defined conditions. In this study, both vancomycin and metronidazole affected microbial metabolism to a considerable extent. Both substances may thus be responsible for disturbances of colon function in vivo. PMID- 11778151 TI - [Endoscopic mucosal resection of premalignant lesions of the upper gastrointestinal tract]. AB - BACKGROUND: Surgical therapy of early malignancies of the upper gastrointestinal tract is associated with substantial morbidity and mortality, especially in elderly and co-morbid patients. In Japan endoscopic mucosal resection (EMR) has been proven to be safe and efficacious in this indication. PATIENTS AND METHODS: 22 patients (68 +/- 14 years, 9 females) with high-grade dysplasia of the esophagus (n = 5), early carcinoma of the esophagus (T1N0M0, n = 11) or early gastric cancer (T1N0M0, n = 6) proven by high-resolution videoendoscopy (plus chromoendoscopy in most cases), miniprobe-endosonography (12-20 MHz) and biopsy were enrolled. The lesion size ranged from 7-40 mm in diameter. EMR was performed using a monofile snare, in almost all cases after submucosal injection of an attenuated epinephrine-solution (1:20,000) to effect a lifting sign. "En bloc" resection was possible in 17/22 cases (77 %), but in 5 patients piecemeal resection had to be performed due to a larger lesion size. RESULTS: Active bleeding occurred on 14 of 22 occasions (64 %), in another 5 patients secondary bleeding (within 24 h after EMR) were detected. All these events could be managed endoscopically (mainly by hemoclip application) and blood transfusion was not required. Other complications did not occur. A complete resection (R0) was achieved in 21/22 cases, however, one patient had to undergo a second EMR procedure because histology of the first resected specimen had revealed malignant infiltration of the resection margin (R1). After the second EMR procedure complete (R0)-resection was obtained. Compared to the histological findings after EMR the pre-procedural staging proved to be correct in all cases. The control examinations (clinical exam, lab data, endoscopy with multiple biopsies, endosonography and CT) after EMR revealed no local or systemic cancer recurrence in 21/22 patients (median follow-up 5 months, range 3-12 months). However, in one patient with adenocarcinoma and Barrett-esophagus another mucosal adenocarcinoma was detected 3 months after EMR (located in opposite to the initial carcinoma treated with EMR). CONCLUSION: EMR seems to be a safe and effective (regarding local tumor control) therapy for high-grade dyplasia and early malignancies in the upper gastrointestinal tract. However, long-term follow-up in these patients has to be awaited. PMID- 11778152 TI - Indirect evidence that intestinal bile salt absorption in rats and hamsters is under positive feedback control. AB - Bile salts are reabsorbed from the intestine by active and passive transport mechanisms with great efficacy. Conflicting data do not allow to judge for certainty whether bile salt absorption is under negative or positive feedback control. To address this issue, we analyzed bile salt absorption in vivo along the entire intestinal tract of rats and hamsters that received intraduodenal bile salt infusions for 54 h following interruption of the enterohepatic circulation. Taurocholate absorption in rats was complete, even when unphysiologically high concentrations of taurocholate were given. The combined infusion of taurocholate together with potent inhibitors of bile salt synthesis such as deoxycholate, taurodeoxycholate or taurochenodeoxycholate, failed to inhibit bile salt absorption. In the hamster, taurochenodeoxycholate and taurocholate absorption was complete and could not be inhibited when given in supraphysiological concentrations. Finally, taurocholate absorption was not impaired when deoxycholic acid was infused. These results provide indirect evidence that bile salt absorption is under positive feedback control regulated by luminal bile salt concentrations. PMID- 11778153 TI - [Guidelines of the German Society of Digestive and Metabolic Diseases for treatment of dyspepsia]. PMID- 11778154 TI - Self-expanding metallic stents for continuous dilatation of benign stenoses in gastrointestinal tract - first results of long-term follow-up in interim stent application in pyloric and colonic obstructions. AB - The use of self-expandable metallic stents (SEMS) is an established palliative treatment of malignant stenosis in the gastrointestinal tract. There is wide experience with the palliation of malignant esophageal obstruction and fistulae, but the application of stents in benign stenosis is rarely reported and exclusively deals with obstruction of the esophagus. No data has been available for benign gastric outlet and rectosigmoid obstruction until now. For the first time we report about 4 cases, in which we temporarily implanted a SEMS (Ultraflex(R) stent, Boston Scientific Microvasive(R)) in benign stenosis of the pylorus or rectosigmoid between 09.97-07.98. The indications for stent implantation were failure of established dilatation therapy and/or refusal of surgical treatment, and/or surgical high-risk patients. Our idea was to prolong the duration of the dilatation by interim implantation (range 8 days - 12 weeks) of a SEMS. There where no peri-interventional complications or dislocations. In one case endoscopic removal was not possible, peranal surgical approach allowed the removal of the stent. During follow-up (range 34-39 months) 2 patients needed one bougienage directly after stent removal. Endoscopic examinations showed no recurrence of any stenosis in all patients. We conclude that interim application of SEMS in benign stenosis of the gastrointestinal tract may be a possible therapeutic tool in selected patients. Further trials with greater numbers of patients dealing with the questions of duration of stay of SEMS and choice of stent type are needed. PMID- 11778155 TI - [Spontaneous rupture of a pancreatic pseudocyst into the portal vein]. AB - HISTORY AND ADMISSION FINDINGS: A 69-year-old woman complained of recurrent cramp like symptoms in the upper abdomen. She admitted excessive alcohol intake. Physical examination revealed swelling and inflammation of both ankles. All other findings were unremarkable. INVESTIGATIONS: Sonography and computed tomography scan showed a cystic structure (5 cm) in the head of the pancreas. Biochemical testing revealed an anemia (Hb 7,5 mg/dl) and an elevated serum lipase (4494 U/l). Intestinal hemorrhage could not be confirmed by endoscopy. An involvement of parapancreatic structures with the pseudocyst could not be demonstrated by combination of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT). COURSE: The patient died unexpectedly. Autopsy showed a rupture of the pancreatic pseudocyst into the portal vein leading to portal vein thrombosis. The cause of death was an embolism of the pulmonary arteries. Postmortal reevaluation of CT and ERCP clarified diagnostic features. CONCLUSION: Erosion of peripancreatic vessels is one of the life threatening complications in chronic pancreatitis. The complication is uncommon but should be included into differential diagnosis of recurrent intestinal bleeding. PMID- 11778156 TI - [Acne inversa in Crohn's disease]. AB - We report 2 patients with the association of Crohn's disease and acne inversa (= hidradenitis suppurativa). A 50-year-old woman with a 10-year-history of Crohn's disease developed suppurative nodules and abscesses in the genitoanal region. Over several years these lesions were hidden from everybody including the family physician. In a 42-year-old female patient abscesses appeared in the axilla 4 years after the diagnosis of Crohn's disease. During the next years these draining lesions also developed in both groins and the perineum. The differential diagnosis included cutaneous manifestations of Crohn's disease in both cases. The clinical picture with draining abscesses and sinuses with communicating channels, cystic nodules, hypertrophic scars and foul-smelling discharge were typical findings of acne inversa. In the last years this entity was reported several times in patients with Crohn's disease. Acne inversa starts with a compact hyperkeratosis of the infundibulum in terminal hair follicles, followed by a segmental rupture of the follicular epithelium and a spreading inflammatory reaction. As pathogenic factors genetic disposition and smoking were discussed. The only curative therapy is excision of the affected area. The reported association should be known in order to recognize the disease and institute the right therapy. PMID- 11778157 TI - Hepatosplenomegaly and progressive neurological symptoms - Late manifestation of Niemann-Pick disease type C - a case report -. AB - Niemann-Pick disease type C is an inborn error of metabolism that affects lipid degradation and storage. Hepatosplenomegaly and progressive neurological symptoms are the main clinical features. We present a case of an adult-onset type of Niemann-Pick disease in a 33-year-old woman who initially presented with dysarthria. At first, laboratory findings suggested Wilson's disease. Laparoscopy showed macroscopic signs of liver cirrhosis and histology did not confirm Wilson's disease. After bone marrow biopsy showed characteristic sea-blue histiocytes, Niemann-Pick disease was suspected and confirmed by filipin stain of cultured fibroblasts. Though rarely encountered, lipid storage disease should be suspected especially in younger patients with organomegaly and progressive signs of neurologic disease. PMID- 11778158 TI - [Current status of cell-based therapies in liver diseases]. AB - Major strides have been made during the past 10 years in the fields of liver cell transplantation and liver-directed gene therapy. Pre-clinical studies in animals have shown that primary hepatocytes transplanted into the liver as well as intravenously transfused bone marrow stem cells can generate new liver tissue. Such cell transplantation studies have contributed to our understanding of organogenesis and hepatocyte biology. Furthermore, transplantation of xenogenic hepatocytes has led to the development of new small animal models for studying viral hepatitis. In the clinical setting, liver cell transplantation offers a wide range of potential therapeutic applications, especially in metabolic diseases. In particular, the case of a patient with Crigler-Najjar Syndrome Type I clearly demonstrated the long-term viability of transplanted hepatocytes with stable metabolic function. Further studies are warranted to assess the full potential of cell- based therapies and their clinical application. PMID- 11778159 TI - [Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer]. PMID- 11778160 TI - A 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly. AB - Studies in mouse and chick have shown that the 5' HoxD genes play major roles in the development of the limbs and genitalia. In humans, mutations in HOXD13 cause the dominantly inherited limb malformation synpolydactyly (SPD). Haploinsufficiency for the 5' HOXD genes has recently been proposed to underlie the monodactyly and penoscrotal hypoplasia in two children with chromosomal deletions encompassing the entire HOXD cluster. Similar deletions, however, have previously been associated with split-hand/foot malformation (SHFM), including monodactyly. Here we report a father and daughter with SPD who carry a 117-kb microdeletion at the 5' end of the HOXD cluster. By sequencing directly across the deletion breakpoint, we show that this microdeletion removes only HOXD9 HOXD13 and EVX2. We also report a girl with bilateral split foot and a chromosomal deletion that includes the entire HOXD cluster and extends approximately 5 Mb centromeric to it. Our findings indicate that haploinsufficiency for the 5' HOXD genes causes not SHFM but SPD and point to the presence of a novel locus for SHFM in the interval between EVX2 and D2S294. They also suggest that there is a regulatory region, upstream of the HOXD cluster, that is responsible for activating the cluster as a whole. PMID- 11778162 TI - The effect of plate luting on reduction accuracy and biomechanics of acetabular osteotomies stabilized with 2.7-mm reconstruction plates. AB - OBJECTIVE: To compare the accuracy of reduction and biomechanical characteristics of acetabular osteotomies repaired with luted and nonluted reconstruction plates. STUDY DESIGN: In vitro study. ANIMALS: Pelves removed from 12 adult greyhounds. METHODS: Acetabular osteotomies were created and repaired with a 6-hole, 2.7-mm reconstruction plates in 24 cadaver hemipelves. Ten hemipelves each were assigned to group I and group II. An impression cast of each acetabulum in group I was made before luting (preluting cast). Group I plates were then elevated, luted, and replaced. A second cast of each acetabulum in group I was then made (postluting cast). Step, gap, and total areas of articular osteotomy incongruence were determined from the casts. Group I (luted plate repairs) and group II (nonluted plate repairs) hemipelves were loaded ventral-to-dorsal using a materials-testing machine. Stiffness, yield load, and maximal load sustained were determined. RESULTS: Mean gap and total area of articular osteotomy incongruence for group I preluted plate repairs (7.1 mm(2) and 8.6 mm(2), respectively) were significantly greater than for group I postluted plate repairs (4.1 mm(2) and 5.1 mm(2), respectively). Mean stiffness and maximal load for group I (681 N/mm and 2,555 N, respectively) were significantly greater than for group II (360 N/mm and 1,730 N, respectively). Mean step area and mean load at yield values were not significantly different between groups. CONCLUSIONS: Luted plate repairs of osteotomized acetabulae result in improved reduction and are stiffer and stronger than nonluted plate repairs. CLINICAL SIGNIFICANCE: Plate luting may improve the accuracy of reduction of acetabular fractures where anatomic reduction is required. Plate luting may also increase the stiffness and strength of fracture repairs and arthrodeses. PMID- 11778163 TI - Comparison of multistage versus one-stage destabilization of a type II external fixator used to stabilize an oblique tibial osteotomy in dogs. AB - OBJECTIVE: To compare the biomechanical effects of multistage versus one-stage destabilization of a type II external skeletal fixator (ESF) used to stabilize an oblique unstable tibial osteotomy in dogs. STUDY DESIGN: In vitro, in vivo, and ex vivo experimental study. ANIMAL POPULATION: Twelve healthy adult dogs. METHODS: The biomechanical characteristics of the type II ESF used in this study were determined. This fixator was applied to both tibiae of two groups of 6 dogs to stabilize a 2-mm-wide oblique osteotomy. One fixator on each dog remained unchanged throughout the 11-week study (control group). The fixator on the opposite limb was destabilized late and acutely in one group of dogs (single stage) and early and progressively in the other (multistage). Clinical examination, radiographic examination, and force-plate analysis were used to evaluate the results. All dogs were euthanatized at 11 weeks. All tibiae were scanned to determine the cross-sectional area of the callus in the center of the osteotomy and subjected to biomechanical tests to determine mean pull-out strength of pins and callus strength and stiffness. RESULTS: Stiffness of the type II ESF used in this study was 578 N/mm in axial compression, 0.767 Nm/deg in torsion, 261 N/mm in medio-lateral bending, and 25 N/mm in cranio-caudal bending. Peak vertical forces of the hindlimbs were significantly lower at 2.5 and 5 weeks than before surgery. Peak vertical forces of the hindlimbs did not change before and after destabilization. No significant differences could be detected between the two destabilization sequences or between all control tibiae and pooled destabilized tibiae with regards to radiographic evaluation of the healing osteotomy, cross-sectional periosteal callus area, mean pull-out strength of transfixation pins, callus strength, and callus stiffness. CONCLUSIONS AND CLINICAL RELEVANCE: Bone healing of unstable osteotomies stabilized with a type II ESF is not significantly enhanced by staged destabilization of the fixation as performed in this study. PMID- 11778164 TI - Evaluation of lameness associated with arthroscopy and arthrotomy of the normal canine cubital joint. AB - OBJECTIVE: To evaluate gait, range of motion (ROM), and lameness in normal dogs after arthroscopy or arthrotomy of the cubital joint. STUDY DESIGN: Experimental study. ANIMALS: Fourteen mature, healthy dogs. METHODS: Dogs were randomly assigned to treatment groups. Seven underwent arthrotomy and 7 underwent arthroscopy of the left cubital joint. Dogs were evaluated using kinetic gait assessment, subjective evaluation scores, and cubital joint ROM. Evaluations were performed before and on days 2, 4, 7, 15, 22, and 29 after surgery. Radiographs made before and after the surgical procedures were evaluated. RESULTS: Significant differences in peak vertical force and vertical impulse force were not observed between surgery groups (P =.88 and.49, respectively). Joint ROM was not significantly different between groups (P =.09 for flexion and.91 for extension). For all dogs, joint ROM and radiographic evaluations remained normal throughout the study period. Significant differences in subjective lameness scores, weight bearing, or pain were not observed between groups (P >/ or =.19 for all variables). CONCLUSIONS: In this study population, significant differences between dogs undergoing arthroscopy or arthrotomy of the cubital joint with respect to postoperative pain, weight bearing, joint ROM, or temporal improvement of ground reaction forces were not observed. CLINICAL RELEVANCE: The results of this study suggest that postoperative morbidity should not be a factor when making a decision to perform either arthroscopy or arthrotomy for exploration of the medial compartment of the canine cubital joint. PMID- 11778165 TI - Microvascular free tissue transfer of the rectus abdominis muscle in dogs. AB - OBJECTIVE: To assess donor-site morbidity and survival of the rectus abdominis muscle with an overlying skin graft after free tissue transfer to a medial femorotibial defect in dogs. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Phase 1: 6 canine cadavers; phase 2: 7 adult mixed-breed dogs. METHODS: Phase 1: The rectus abdominis muscle was removed from canine cadavers, muscular and vascular dimensions were recorded, and angiography was performed. Phase 2: Muscular transfer was performed through anastomosis of the caudal epigastric artery and vein to the saphenous artery and medial saphenous vein. Transferred tissues were evaluated on postoperative days 3, 6, 10, and 13. Animals were examined daily until euthanasia between postoperative days 31 and 42. Postmortem angiograms were performed and tissues collected for histopathologic evaluation. RESULTS: Phase 1: Appropriate vascular dimensions for microvascular anastomosis were confirmed and surgical technique perfected. Phase 2: Muscular excision produced minimal donor-site morbidity. All muscles survived after microvascular transfer and angiography confirmed vascular patency. All of the skin grafts survived, with one graft undergoing partial necrosis. CONCLUSIONS: The rectus abdominis muscle can be successfully transferred to a medial femorotibial defect and can serve as a bed for acute skin grafting. No significant donor-site morbidity is associated with its removal. CLINICAL RELEVANCE: Microvascular free tissue transfer of the canine rectus abdominis muscle has not been previously described. This technique provides a new alternative for repair of appropriate wounds. Additional studies are needed to define its utility in clinical patients. PMID- 11778166 TI - Analysis of factors affecting survival in dogs with aortic body tumors. AB - OBJECTIVE: To evaluate the effect of perioperative and operative variables on survival time in dogs with aortic body tumors. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Twenty-four client-owned dogs with histologically confirmed aortic body tumor. METHODS: Seventy-eight patient records of dogs seen at the University of Illinois Veterinary Teaching Hospital between 1989 and 1999 with a diagnosis of a heart-base mass were reviewed. Dogs without histologic conformation of an aortic body tumor were excluded. Age; sex; breed; the presence of pleural effusion, pericardial effusion, or abdominal effusion; evidence of cardiac arrhythmias; evidence of distant metastasis; treatment with pericardectomy; treatment with chemotherapy; and time from diagnosis until euthanasia or death were recorded on a spreadsheet. Cox proportional-hazard ratios were used to calculate the relationship of risk variables to survival time. Median survival time was determined using life-table analysis. RESULTS: Twenty-four dogs met the criteria for inclusion in the study. The median age of dogs with aortic body tumors was 9 years. All dogs had a surgical biopsy performed. Fourteen dogs had a pericardectomy at the time of the biopsy procedure. Of all factors analyzed, only treatment with pericardectomy had a significant influence on survival (P =.0029). Dogs that had pericardectomy survived longer (median survival, 730 days; range, 1-1,621 days) compared with dogs that did not have pericardectomy (median survival, 42 days; range, 1-180 days). This finding was independent of the presence or absence of pericardial effusion at the time of surgery. CLINICAL RELEVANCE: Dogs that are diagnosed with aortic body tumors may benefit from a pericardectomy at the time of surgical biopsy. PMID- 11778167 TI - Evaluation of the clinical and histologic features of renal allograft rejection in cats. AB - OBJECTIVES: To describe the clinical signs and histopathologic features of renal allograft rejection in cats, and to provide a historical, untreated control group for use in future studies of feline renal allograft rejection. ANIMALS: Fourteen adult research cats. METHODS: Renal transplantation and bilateral nephrectomy were performed in pairs of immunogenically mismatched cats. A physical examination was performed, and packed cell volume, total protein, and plasma creatinine concentrations were measured each day after surgery. The cats were euthanatized when plasma creatinine concentration exceeded 7 mg/dL or when weight loss exceeded 20%. Renal histopathology was scored according to the Banff 97 criteria by 3 pathologists. RESULTS: Nine cats completed the study. Plasma creatinine exceeded 7 mg/dL in 5 cats, weight loss exceeded 20% in 3 cats, and 1 cat was found dead. Clinical signs in cats with rejection were nonspecific or absent. Rectal temperature decreased by 0.8 +/- 0.5 degrees C in the 24 hours before euthanasia. The pathologists agreed on the allograft histopathologic category in 6 of 9 cats. The histologic consensus was acute/active rejection in 8 cats and normal in 1 cat. Median survival time of the 8 cats with histologically confirmed allograft rejection was 23 days (range, 8-34 days). CONCLUSIONS AND CLINICAL RELEVANCE: Renal allograft rejection is associated with minimal clinical signs. Therefore, plasma creatinine concentration should be measured routinely in patients with a functioning allograft. An increase in plasma creatinine concentration is highly suspicious for allograft rejection, although a biopsy of the renal allograft is needed for definitive diagnosis. PMID- 11778168 TI - Radical lateral body-wall resection for fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap: a prospective clinical study of the technique and results in 6 cats. AB - OBJECTIVE: To describe and evaluate a technique for radical resection of the lateral body wall for treatment of fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap in cats. STUDY DESIGN: Prospective, clinical study. ANIMALS OR SAMPLE POPULATION: Six client-owned cats with fibrosarcoma. METHODS: Six cats with histologically confirmed fibrosarcoma of the lateral body wall were staged using radiography and/or computer tomography scanning. Preoperative radiotherapy was used in 3 cats. All cats had the lateral abdominal wall resected and reconstructed with polypropylene mesh. A caudal superficial epigastric flap was mobilized and rotated to close the skin deficit. The animals were evaluated after surgery for wound complications, tumor recurrence, and metastasis. Outcome was assessed by patient examination and client consultation. RESULTS: Minor dehiscence of the skin flaps occurred in 2 cats, and 1 other cat was successfully resuscitated from respiratory and cardiac arrest after surgery. All tissue specimens were tumor free at the surgical margins. Follow-up times ranged from 12 to 21 months, with a mean time of 17.2 months. None of the cats had evidence of local tumor recurrence or metastasis; outcome was judged good to excellent in all cats. CONCLUSIONS AND CLINICAL RELEVANCE: Radical lateral body-wall resection and reconstruction is an effective technique for achieving local tumor control with acceptable patient morbidity. Further studies are needed to assess whether the technique will result in improved tumor-free intervals and survival times. PMID- 11778169 TI - Comparison of fine-needle aspiration and surgical-tissue biopsy in the diagnosis of canine brain tumors. AB - OBJECTIVE: To compare the diagnoses obtained using fine-needle aspiration (FNA) and surgical-tissue biopsy of focal cerebral masses with the histologic diagnoses obtained via necropsy. STUDY DESIGN: A prospective case series. SAMPLE POPULATION: Ten client-owned adult dogs of various breeds. All dogs had clinical signs of cerebral disease and had a focal brain mass identified using magnetic resonance imaging; all were eventually euthanatized. METHODS: Immediately after euthanasia, the brains were removed en bloc from the cranial cavity. FNAs were obtained from each mass using a 22-gauge hypodermic needle and a 12-mL syringe. Cytologic preparations were made from each aspirate. A 14-gauge Tru-cut biopsy needle was used to obtain a core tissue sample from each mass. The biopsy specimens were fixed in 10% buffered formalin and submitted for histologic evaluation. The brains were similarly fixed and stained. Six-micrometer-thick transverse sections of the brain were examined microscopically. RESULTS: Neoplasia was confirmed in all dogs histologically in the 6-microm transverse sections. Four meningiomas, 2 astrocytomas, 2 oligodendrogliomas, 1 pituitary adenocarcinoma, and 1 neurofibrosarcoma were identified. FNA correctly identified all of the masses as neoplastic. Cytologic diagnoses correlated with the histologic interpretation in 5 of the masses (50%). Tru-cut biopsy specimens identified all 10 masses as neoplastic; in 9 of the 10 (90%), the diagnosis correlated with the histologic diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: FNA is a sensitive method that can be used to determine the presence of neoplasia in the brain, but is not as definitive as the Tru-cut biopsy in determining the specific type of cerebral neoplasm. PMID- 11778170 TI - Limb sparing using a double bone-transport technique for treatment of a distal tibial osteosarcoma in a dog. AB - OBJECTIVE: To evaluate the treatment of a spontaneously occurring osteosarcoma in a dog by means of tumor resection and bone regeneration of a 12-cm defect using double bone transport. STUDY DESIGN: Case report. ANIMALS OR SAMPLE POPULATION: An 11 year-old client-owned German shepherd. METHODS: After tumor resection, a preassambled Ilizarov frame was secured to the proximal tibia and to the tarso metatarsal region. Two osteotomies were performed in the proximal metaphysis. The two bone segments were transfixed with 1.5-mm-diameter wires, each secured to a ring, and bone transport was performed until the distal segment reached the talar surface. Cisplatin was administered 14, 35, and 59 days after surgery. RESULTS: Bone regenerate was first visible radiographically 4 weeks after surgery. The frame was removed 162 days after surgery. The hock was protected with a plaster cast because the tarsal arthrodesis was not complete. The dog underwent tibiotarsal arthrodesis 201 days after osteosarcoma resection. The dog died of metastatic disease 239 days after the initial surgery. CONCLUSIONS: Even though this dog died of systemic metastases, local recurrence did not develop. Cisplatin chemotherapy did not appear to negatively affect bone regeneration. CLINICAL RELEVANCE: To our knowledge, the double transport technique has not been previously described in the veterinary literature. In this dog, this technique decreased the duration of treatment compared with a conventional single-segment transport technique. PMID- 11778171 TI - Evaluation of 5 types of fishing material, 2 sterilization methods, and a crimp clamp system for extra-articular stabilization of the canine stifle joint. AB - OBJECTIVE: To evaluate the mechanical properties of 5 types of fishing material, 2 sterilization methods, and a commercially designed crimp-clamp system for the extra-articular repair of the canine stifle joint. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Animals were not used in this study. METHODS: Two brands of monofilament nylon fishing line and 3 brands of monofilament nylon leader line were used to determine the effect of steam and ethylene oxide sterilization on strength and elongation of the material. A strand of 36-kg test monofilament nylon fishing material was wrapped around 2 rods or knotted to form a loop around 2 rods on a materials-testing machine. Ten trials of each brand of unsterilized, steam-sterilized, and ethylene oxide-sterilized fishing material were tested. A strand of each material was elongated to failure at a constant displacement of 1,000 mm/min to determine strength. A strand of each material was cycled 10 times to a load of 50 N to determine percent elongation. The brand of fishing material with the greatest strength and least elongation was crimped to form a loop around 2 rods on a materials-testing machine and tested as described above. ANOVA was used to determine the effect of sterilization method, brand of material, knot, wrap, and crimp on strength and elongation of the material, and a post-hoc t test was used when significant differences were found. A Student t test was used to compare fixation techniques (wrap, knot, and crimp). RESULTS: Sterilization by steam or ethylene oxide had no significant effect on the strength of the nylon fishing material. Steam sterilization resulted in significant increases (2- to 4-fold) in elongation of most nylon fishing material when compared with unsterilized material. Ethylene oxide sterilization had minimal effect on elongation of the fishing material. Mason leader line showed no significant change in strength or elongation regardless of sterilization method. Significantly less strength and significantly less elongation were demonstrated in Mason leader line that was crimped as compared with Mason leader line that was knotted. CONCLUSION: Ethlylene oxide was the preferred method of sterilization to preserve strength and minimize elongation of the fishing material. Of the materials tested, Mason leader line had the least elongation and the greatest preservation of strength when ethylene oxide was used as the sterilization method. Mason leader line and Sufix fishing line were comparable choices when steam was used as the sterilization method. Significantly less elongation was demonstrated in crimped Mason leader line as compared with knotted Mason leader line. CLINICAL RELEVANCE: Of the materials tested, Mason leader line and Sufix fishing line had the best mechanical properties for extracapsular stabilization of the canine stifle joint. Crimping is an attractive alternative to knotting and results in a reduction in elongation of the nylon fishing material. PMID- 11778173 TI - The prevalence of malignant neoplasia in feline renal-transplant recipients. AB - OBJECTIVE: To determine the prevalence of malignant neoplasia in a group of feline renal-transplant recipients (FRTR). STUDY DESIGN: Retrospective clinical study. ANIMALS: Ninety-five consecutive client-owned FRTR treated at the University of California, Davis, between 1987 and 1997. METHODS: Medical records of the 95 cats were examined. The time to occurrence and type of malignant neoplasia, if present, was determined. RESULTS: Nine of 95 cats (9.5%) developed apparently de novo malignant neoplasia after receiving renal allografts. The predominant type of neoplasm was lymphoma. The median time to diagnosis of neoplasia in these 9 patients was 9.0 months after transplantation, whereas the median survival time was 14.0 months after transplantation. This compares with a median survival time of 22 months after transplantation for cats that died for reasons other than development of malignant neoplasia. CONCLUSIONS: Although these transplant recipients were not compared with a control population, it would appear that, as in humans, malignant neoplasia is encountered with greater-than expected frequency after renal transplantation and immunosuppression in cats. CLINICAL SIGNIFICANCE: The apparent propensity to develop malignant neoplasia after renal transplantation and immunosuppression in cats is a fatal complication of which owners and clinicians should be aware. PMID- 11778172 TI - Arthrodesis of the equine proximal interphalangeal joint: a biomechanical comparison of two 7-hole 3.5-mm broad and two 5-hole 4.5-mm narrow dynamic compression plates. AB - OBJECTIVE: To compare the biomechanical characteristics and mode of failure of two different dynamic compression plate (DCP) techniques for proximal interphalangeal joint (PIPJ) arthrodesis in horses. STUDY DESIGN: Randomized block-design blocking on horse (1-5), method of fixation (two 7-hole, 3.5-mm broad DCP vs two 5-hole, 4.5-mm narrow DCP), side (left, right), and end (front, hind). Constructs were loaded to failure in 3-point bending in a dorsal-to-palmar (plantar) direction. SAMPLE POPULATION: Ten paired limbs from 5 equine cadavers. METHODS: Two 7-hole, 3.5-mm broad dynamic compression plates (bDCP) were used in 1 limb of a pair, and two 5-hole 4.5-mm narrow dynamic compression plates (nDCP) were used on the contralateral limb. Plates were positioned abaxially across the dorsomedial and dorsolateral aspect of the PIPJ. Arthrodesis constructs were loaded (19 mm/s) in 3-point bending in a dorsal-to-palmar (plantar) direction using a materials-testing machine. Composite stiffness, yield point, and maximal bending moment at failure were obtained from bending moment-angular deformation curves. Data were analyzed using ANOVA, X(2) analysis, and Fisher's exact tests; the power of the test was calculated when differences were not significant. RESULTS: There were no significant differences in composite stiffness (P >.05; power = 0.8 @ delta = 21.9%), yield point (P >.05; power = 0.8 @ delta = 34.4%), or maximal bending moment (P >.05; power = 0.8 @ delta = 17.8%) between the two fixation techniques. For bDCP constructs, 11% (15 of 140) of the 3.5-mm screws were damaged; 7 of the screw heads pulled through plates where the plates bent, 1 screw head broke off, and 7 screws were bent or pulled out of the phalanx. For nDCP constructs, 8% (8 of 100) of the 4.5-mm screws were damaged; 1 screw head pulled through a plate, 1 screw head broke off, and 6 screws were bent or pulled out of the phalanx. CONCLUSIONS: There were no biomechanical or failure differences between bDCP and nDCP fixation of the PIPJ in horses when evaluated in single-cycle 3-point bending to failure. CLINICAL RELEVANCE: There is no biomechanical advantage to the use of two 7-hole, 3.5-mm bDCP in equine proximal interphalangeal arthrodesis compared with two 5-hole, 4.5-mm nDCP. Two 5-hole, 4.5-mm nDCP may be easier to place, whereas two 7-hole, 3.5-mm bDCP may provide more versatility in fracture repair. PMID- 11778174 TI - [Pathologic diagnosis of usual interstitial pneumonia]. AB - OBJECTIVE: To discuss pathologic differential diagnosis between UIP and the other types of IPF. METHOD: The slides (routine and histochemical stain) of 4 autopsy cases of UIP were reviewed. RESULTS: The most significant characteristic of UIP is that the interstial changes show temporal heterogeneity and variable distribution. The earlier stage of UIP shows an interstitial infiltrate of chronic inflammation cells and the progressive stage appears significant interstitial fibrosis. The honeycomb change and muscular cirrhosis are the characteristics of the end stage. CONCLUSION: For clinical purpose, the distinction of UIP and the other types of IPF is of great significance because of marked differences in the prognosis and therapy. PMID- 11778175 TI - [A retrospective study of 3 cases of nonspecific interstitial pneumonia]. AB - OBJECTIVE: To discuss the clinical features of nonspecific interstitial pneumonia. METHOD: Review of three cases of pathologically proved NSIP with the clinical, radiological, physical and bronchoscopic presentation. RESULTS: Three cases, one male and two females, aged from 49 to 59, presented with a duration of symptoms on diagnosis of 3 to 7 months. Cough, worsening dyspnea and inspiratory crackles were presented in all three cases and intermittent low grade fever in two but none has digital clubbing. There was a history of organic dust exposure in one case and in another case primary Sjogren's syndrome was diagnosed. Patchy ground-glass attenuation with thickening of bronchovascular markings were the main findings in high resolusion computed tomography (HRCT) of all three cases. Small areas of consolidation in two cases and traction bronchiectasis in one were found while there was no honeycombing. Increased bronchoalveolar lavage fluid (BALF) cell recovery and percentage of lymphocytes were found in all cases. The BALF CD4/CD8 ratio was measured in two cases and was markedly decreased in both cases. CONCLUSION: NSIP has some clinical features that are different from UIP and may provide clues to diagnosis. PMID- 11778176 TI - [Effects of dexamethasone on apoptosis and expression of Fas/FasL system in lung tissues of ALI rats]. AB - OBJECTIVE: To determine whether apoptosis occurs in the lung tissues from rats with acute lung injury (ALI), and observe protective effects of dexamethasone by regulating apoptosis of lung tissues in rats with ALI. METHODS: By using TUNEL, in situ hybridization, SqRT-PCR and immunocytochemistry techniques, apoptosis and Fas, FasL expression were studied during early phase of ALI in rats. RESULTS: LPS leads to the rapid appearance of apoptosis in alveolar epithelial cells and pulmonary vascular endothelial cells at early stage of ALI in rats. The expression of Fas, FasL mRNA and protein was up-regulated in lung tissues of rats with ALI. The administration of dexamethasone suppressed apoptosis as well as expression of Fas, FasL mRNA and protein, inhibited TNF-alpha production and abated lung injury. CONCLUSIONS: The excessive apoptosis and Fas/FasL system may play a role in the pathogenesis of LPS-induced ALI in rats. The protective effects of dexamethasone include inhibiting inflammatory mediators production, suppressing the activation of Fas/FasL system and apoptosis in lung tissues of ALI rats. PMID- 11778177 TI - [Significance of the changes of urinary uric acid, ANP, renin and aldosterone in sleep apnea syndrome patients]. AB - OBJECTIVES: To assess the utility of urinary uric acid excretion and urinary uric acid/creatinine ratio as the marker of nocturnal respiratory disturbance in patient with sleep apnea syndrome (SAS) before and after the institution of nasal continuous positive airway pressure (nCPAP). Another purpose is to explore the relationship between the nocturnal diuresis and atrial natriuretic peptide (ANP), renin-aldosterone in SAS. METHODS: 22 cases diagnosed as SAS by polysomnography (PSG) were selected as trial group, 11 cases excluded from SAS by PSG were as control group, and 13 severe SAS patients were treated by nCPAP and taken as nCPAP therapy group. The markers mentioned above were compared in these groups. RESULTS: The overnight change in urinary uric acid/creatinine ratio in trial group is 0.47 +/- 0.31, which is significantly higher than that in control group (0.01 +/- 0.23), P < 0.05, and in nCPAP therapy group after therapy (0.01 +/- 0.19) significantly lower than that before nCPAP therapy (0.48 +/- 0.27), P < 0.001. The morning urinary uric acid excretion in trial group is (5.4 +/- 2.3) mg/L which is also significantly higher than that in control group (3.2 +/- 1.4) mg/L, P < 0.001, and in nCPAP therapy group (3.3 +/- 1.2) mg/L significantly lower than that before nCPAP (5.9 +/- 2.6) mg/L, P < 0.05. The mean morning blood ANP in trial group is (0.182 +/- 0.004) microgram/L, which is higher than that in control group (0.182 +/- 0.004) microgram/L, P < 0.05, and in nCPAP therapy group (0.122 +/- 0.001) microgram/L is much lower than that before nCPAP therapy (0.180 +/- 0.003) microgram/L, P < 0.001. However there are no statistic significant differences between these groups in blood renin-aldosterone. CONCLUSIONS: The urinary uric acid excretion and overnight change in urinary uric acid/creatinine are good markers to determine the effects of nCPAP on SAS. The nocturnal diuresis in SAS patients is correlated with the increase of ANP in plasma. PMID- 11778178 TI - [Study on left ventricular function of chronic obstructive pulmonary diseases in stable phase by using nuclear techniques]. AB - OBJECTIVE: To study the left ventricular function of chronic obstructive pulmonary diseases in stable phase. METHOD: The systolic and diastolic function of the left ventricles of chronic obstructive pulmonary diseases was studied by using gate cardiac blood-pool imaging. RESULTS: There are no statistical significance in left cardiac systolic and diastolic function of the patients with different degrees of chronic obstructive pulmonary diseases and control group of normal lung function on left ventricle ejection fraction(LVEF), peak ejection rate(PER), ejection fraction at one third of TES from end-diastole(1/3EF), ejection fraction rate at one third of TES from end-diastole(1/3ER), time between end-diastole and end-systole(TES), time to peak filling from diastolic to end systole(TPE), peak filling rate(PFR), filling fraction at 1/3(TES) from end systole(1/3FF), filling rate at 1/3 (TES) from end-systole(1/3FR). CONCLUSION: There is no significant difference in left ventricular function in patients with different degrees of chronic obstructive pulmonary diseases in the stable phase. PMID- 11778179 TI - [Study on the antitumor effect of angiostatin on LA795 adenocarcinoma cells]. AB - OBJECTIVE: To study the antitumor effect of angiostatin on LA795 adenocarcinoma cells inoculated on T739 mice. METHODS: Affinity chromatography purified plasminogen was digested by pancreatic elastase and angiostatin was obtained by purifying the digestion with affinity chromatography and dialysis. T739 mice were inoculated with LA795 cells. Angiostatin was given to part of inoculated and uninoculated mice by intraperitoneal injection fourteen days after the inoculation. The treatment lasted 20 days and the size of tumor, survival period, behavior of the mice and pathology of lungs, livers and kidneys were observed. RESULTS: The size of tumor decreased from (2.35 +/- 0.26) cm to (0.97 +/- 0.34) cm after angiostatin treatment. The number of metastases in lung was significantly fewer in angiostatin treated mice than in untreated ones, which lived much shorter. No obvious side effects were observed. CONCLUSION: Angiostatin markedly inhibits the growth and metastasis of LA795 cells on T739 mice and no obvious side effects of angiostatin were found during the treatment. PMID- 11778180 TI - [Transbronchial needle aspiration in routine bronchoscope practice]. AB - OBJECTIVE: To evaluate the yield of transbronchial needle aspiration (TBNA) in a clinical routine bronscopy practice after training under the guide by CT scanning. METHODS: Using Wang TBNA System and CT scanning methods to define the site in airway for puncturing the enlarged mediastinal lymphnode. The positive rate of TBNA was 64%, almost equal to the positive rate (61%) of the method by operating directly under CT scanning. TBNA was performed on 100 consecutive patients with 152 enlarged mediastinal nodes undergoing diagnostic fiberoptic bronchoscopy. RESULT: The positive rate (64%) was equal to the positive rate (61%) under the CT guide. CONCLUSIONS: CT guiding TBNA is very useful for training doctors to learn the TBNA technique, and TBNA can be done very well and play an important role in routine bronchoscope practice. PMID- 11778181 TI - [Studies on pncA gene mutations in M. tuberculosis isolates]. AB - OBJECTIVE: To understand the mutations of pncA gene in M. tuberculosis isolates, and to evaluate their clinical value. METHODS: Analyzing the pncA genes in 74 M. tuberculosis clinical isolates with PCR-SSCP and PCR-AS. M. tuberculosis strain H37Rv was used as control. RESULTS: 32 drug-sensitive isolates all displayed normal pncA SSCP profile. Of 20 non-pyrazinamide-resistant isolates, 4 had abnormal pncA SSCP profile, in which 2 isolates were sequenced, one was TTC-->TTA mutation at codon 58, another was TGG-->CGG mutation at codon 68. Of 22 pyrazinamide-resistant isolates, 10 displayed abnormal pncA SSCP profile, in which 2 isolates sequenced had TTC-->TTA mutation at codon 58. CONCLUSIONS: The mutation of pncA gene is a pyrazinamide-resistant molecular mechanism in M. tuberculosis. Detecting the mutations of pncA genes might diagnose pyrazinamide resistance rapidly in some M. tuberculosis isolates. PMID- 11778182 TI - [Mycobacterium vaccae influences the kinetics of Th1/Th2 cells and expression of iNOS in a marine model of experimental tuberculosis]. AB - OBJECTIVE: To investigate the immunoregulative mechanism of Mycobacterium vaccae by way of molecular pathology. METHODS: BALB/C mice were randomly divided into three groups: tuberculosis model (A); mice were challenged with H37Rv by their tail veins and then immunized by M. vaccae (B); control mice (N). Immunohistochemistry and pathological slices stained with HE were evaluated to investigate the correlation between the expression of IFN-gamma, IL-4 and iNOS and the type and magnitude of tissue injury. RESULTS: A predominance of Th1 cells was observed manifested by a high percentage of IFN-gamma positive cells in the inflammatory infiltrate and granulomas demonstrated by immunohistology peaked 6 weeks after infection (0.058 +/- 0.010), and there was a significant increase compared with N group (0.005 +/- 0.020, P < 0.01). This was followed by a chronic advanced phase characterized by pneumonia local necrosis with a Tho balance due to an equivalent proportion of IFN-gamma and IL-4 positive cells in the lung lesions. The iNOS expression was increased in acute phase and decreased in chronic phase. B group had localized lung lesions, proliferate and lymphoid nodules were predominant, there was less necrostic change. A predominance of Th1 cells was observed during the infection changed over time and there was no Tho balance phase occurred. iNOS expression had a higher level during the wholecourse of infection. CONCLUSION: M. vaccae can enhance the protective immunological response by inducing Th1 response and inhibiting Th2 response. PMID- 11778183 TI - [Studies on 5 kinds of methods combination for detection of smear and culture negative pulmonary tuberculosis]. AB - OBJECTIVE: To evaluate the diagnostic value of 5 kinds of methods used jointly for smear and culture negative pulmonary tuberculosis. METHODS: The high specificity methods were PCR examination for sputum TB-DNA, immunological examination (ELISA method) for serum LAM IgG, PPD IgG, SCIC and PPD 0.1 U skin test. Smear and culture positive cases were 31, smear and culture negative 54, healthy control 53, other lung disease 30. Methods were used for every case synchronously, then the sensitivity and specificity of single method and the diagnostic value of single and joint examination for smear and culture negative patients were evaluated. RESULTS: In single examination sensitivity of PCR, LAM IgG, PPD IgG, SCIC, PPD 0.1 U was 96.8%, 69.2%, 62.1%, 32.0%, 53.8% respectively; specificity was 96.2%, 98.1%, 98.1%, 98.1% correspondingly. The positive detection rate of single examination for sputum TB negative patients was just 21.4%-44.4%. In combination examination the positive rates increased remarkblely by the number combined from 2 to 5, they were 66.9%, 70.5%, 80.4%, 85.7% respectively and they were more notable than that of TB positive group. The specificity of combination examination was slightly decreased by the number combined. It decreased just by 9% and the specificity of most examination methods kept on no less than 90%. CONCLUSIONS: For diagnosis of smear and culture negative pulmonary tuberculosis combination examination using the high specificity methods can increase the sensitivity obviously and the specificity just decrease slightly. It is valuable for widely use of combination method in detection of smear and culture negative patients. PMID- 11778185 TI - [Prospects for tuberculosis control and research in the 21st century]. PMID- 11778184 TI - [Antituberculosis effect of levofloxacin]. AB - OBJECTIVE: Assess the activities of levofloxacin (LVLX) against Mycobacterium tuberculosis both in vitro and in vivo, the pharmacokinetics of LVLX and the effectiveness and safety of it in the treatment of pulmonary tuberculosis, with ofloxacin(OFLX) as control. METHODS: The MIC and MBC of LVLX were determined by the tube doubling dilution method, and the effectiveness of the drugs were assessed by half survival time of the mice. The concentrations of LVLX and OFLX in serum were measured by HPLC. The pharmacokinetic parameters obtained were calculated. 138 newly diagnosed and retreatment pulmonary tuberculosis patients were randomly allocated to receive four chemotherapy regimens. RESULTS: The MIC and MBC of LVLX against Mycobacterium tuberculosis were 2 dilutions lower than that of OFLX, in a murine tuberculosis model, the antimycobacterial activity of LVLX was significant and superior to OFLX with the same dose. The concentration time curves of LVLX and OFLX were conformed to an one-compartment model. There was no significant difference between the two formulations in the Tmax, T1/2 and 1/2 Cmax, 1/2 AUC of OFLX and LVLX. The sputum conversion rates at the end of treatments of groups I, II, III and IV were 97%, 97%, 82% and 84% respectively. X ray resolution rates were 97%, 94%, 88% and 88% respectively. The side effects of four groups were rather low. CONCLUSIONS: LVLX displays powerful activities against Mycobacterium tuberculosis both in vitro and in vivo, which is two times that of OFLX.LVLX and OFLX have the same good pharmacokinetic characteristics. LVLX at the dose of 300 mg/d shows the same effectiveness and fewer adverse drug reactions in comparison with OFLX at the dose of 600 mg/d in the treatment of pulmonary tuberculosis. So LVLX is a new effective and safe antituberculosis drug. PMID- 11778186 TI - [Repair of spontaneous rupture of esophagus by pedicled greater omentum (10 cases report)]. AB - OBJECTIVE: To evaluate the effect of various covering tissues for improving the cure rate of spontaneous rupture of esophagus. METHODS: From 1970 to 1994, 13 cases with spontaneous rupture of esophagus were performed primary repair, among them, 10 cases were covered by pedicled greater omentum after impair, and the other 3 cases were covered by pedicled pleural flap. RESULTS: Satisfactory result and complete recovery were obtained in all 10 cases by using pedicled greater omentum. Two cases among 3 cases using pedicled pleural flap suffered re-rupture of esophagus at 5 days and 8 days after operation, and died because of whole body exhaustion. CONCLUSION: Pedicled greater omentum is a good covering tissue for repair of spontaneous rupture of esophagus. PMID- 11778187 TI - [Microwave effect on immunological response of chronic limb lymphedema]. AB - OBJECTIVE: To observe the character of local and systemic immune responses in chronic limb lymphedema, and to investigate the effect of microwave on immunological response. METHODS: From November 1996 to February 1998, 27 patients with chronic limb lymphedema were adopted in this study. Among them, there were 11 males and 16 females, the average age was 36.6 years. These patients were classified as the experimental group and 10 healthy volunteers as the control group. Before and after microwave heating and bandaging treatment, T and B lymphocyte in peripheral blood and skin infiltrating cells in the patients and volunteers were detected and phenotyped with alkaline phosphatase-anti-alkaline phosphatase(APAAP) and avidin biotin peroxidase complex (ABC) immunohistochemical methods respectively. RESULTS: There were decreases of CD4+ T lymphocyte and the ratio of CD4+/CD8+ in peripheral blood and predominant dermal perivascular T lymphocyte infiltration in chronic limb lymphedema patients. After two courses of microwave heating and bandaging treatment, it was found that the number of CD4+ T lymphocytes increased and the ratio of CD4+/CD8+ was restored to normal levels, and dermal perivascular T lymphocyte infiltration decreased greatly. CONCLUSION: Microwave heating and bandaging treatment can modulate the systemic and local immunological imbalance of chronic limb lymphedema. PMID- 11778188 TI - [Materials fabrication of tissue engineered peripheral nerve in vitro]. AB - OBJECTIVE: To investigate the methods to fabricate repair materials of tissue engineered peripheral nerve with bioactivity of Schwann cells (SC). METHODS: 1. The materials were made by dry-wet spinning process to fabricate PLA hollow fiber canal with external diameter of 2.3 mm, internal diameter of 1.9 mm, thickness of 0.4 mm, pore size of 20 to 40 microns, pore ratio of 70% and non-spinning fiber net with pore size of 100 to 200 microns, pore ratio of 85%. 2. SC were implanted into excellular matrix (ECM) gel to observe the growth of SC. 3. SC/ECM complex were implanted into non-spinning PLA fiber net to observe the growth of SC. 4. SC, SC/ECM and SC/ECM/PLA were implanted into PLA hollow fiber canal to bridge 10 mm defect of rat sciatic nerve. RESULTS: 1. SC were recovered bipolar shape at 1 day after implantation, and could be survived 14 days in ECM gel. 2. After SC/ECM complex was implanted into PLA net, most of SC were retained in the pore of PLA net with the formation of ECM gel. SC could be adhered and grown on PLA fiber. 3. Most of SC in ECM gel could be survived to 21 days after transplantation. Survival cell numbers of SC/ECM and SC/ECM/PLA groups were obviously higher than SC suspension group. CONCLUSION: Non-spinning PLA porous biodegradable materials with ECM is benefit for SC to be adhered and grown. PMID- 11778189 TI - [The xenoantigenicity of Chinese inbred-line pigs]. AB - OBJECTIVE: The major obstacle in pig to human transplantation is acute and hyperacute rejection (HAR) triggered mainly by alpha-galactosyl residues(alpha Gal) in donor. Since the inbred-line Banna pig(IBNP) and Wuzhishan pig (IWZSP) are highly inbred and may be the potential donor for xenotransplantation, it is important to investigate the reaction between human serum and inbred-line pig tissues as well as the distribution of alpha-Gal in these tissues. METHODS: Samples from heart, liver, spleen, lung, kidney, pancreas, small intestine, thymus, skin, lymph node and blood vessels at all levels were collected from four 8 to 11-month-old male IBNPs and one IWZSP. Affinity-immunohistochemistry assays were conducted following routine procedures on paraffin sections with normal human sera of blood type A, B, O, AB and BSI-B4(alpha-Gal specific binding lectin) as the primary antibodies or affinity reagents. Sections digested by alpha-galactosidase were also examined as control. RESULTS: Parallel results were obtained from these pig tissues stained against human sera and BSI-B4. There was no significant difference both in the antigens recognized by sera of different blood types or BSI-B4 and in the distribution of alpha-Gal. The strongest alpha Gal positive staining was appeared in vascular endothelial cells at all levels and partial parenchyma cells. However, tissues of cartilage, peripheral nerve and muscle were negative. After digested by alpha-Galactosidase, all samples were negative against BSI-B4 and human sera except few positions that showed different staining. CONCLUSION: The distribution of target antigen is similar in various tissues of the two kinds of pigs. Though alpha-Gal is the major xenoantigen in IBNP and IWZSP, there may be some unknown antigens related to pig to human transplantation. Possibly the level and distribution of antigen expression in pig tissues are not the first affair to be considered, and these pigs should be genetically modified in order to eliminate rejection in pig to human xenotransplantation. PMID- 11778190 TI - [Total wrist arthroplasty]. AB - OBJECTIVE: To review the history and current status of total wrist arthroplasty. METHODS: The original articles about wrist arthroplasty in recent years were reviewed. RESULTS: The properties of wrist prosthesis of different generations were reviewed, with the emphasis on the prosthesis design and biomechanical behaviours. The surgical techniques, complications and salvage procedures were also discussed. CONCLUSION: Although wrist arthrodesis is highly successful in treating the end-stage wrist arthritis, total wrist arthroplasty using well designed prosthesis remains an alternative for the patients with special demands of hand functions. PMID- 11778191 TI - [Research progress of fibroblast and wound repair]. AB - OBJECTIVE: To review the recent advances in fibroblast study and its role in wound repair. METHODS: Recent original articles related to wound repair were retrieved extensively, and the effect of fibroblast on every stages of repair were summed up and comprehended. RESULTS: Fibroblast plays important roles in granulation formation, wound contraction, matrix synthesis, wound repair, scar formation and scarless repair by means of growth factors modulation. CONCLUSION: The understanding of fibroblast in the wound repair can promote the progress of biological therapy of wound repair and scar prevention. PMID- 11778192 TI - [Double semitendinous reconstruction of posterior cruciate ligament with invasive mini-plate technique]. AB - OBJECTIVE: To probe the clinical results of a new designed operation-double semitendinous reconstruction of posterior cruciate ligament (PCL) with invasive mini-plate. METHODS: The new surgical technique was performed on 28 patients with PCL deficient knee in our department from September 1994 to October 1997. Protection of popliteal nerves and blood vessels was emphasized in the operation, and the femoral and tibial tunnel placement was critical to the procedure's success. RESULTS: All patients were followed up 18 to 36 months, averaged 22 months, they gained stable knees. The knee function of 28 patients recovered to normal after the operation, 1 patients had a small range of limitation of the knee flexion, but no obvious dysfunction. CONCLUSION: Double semitendinous reconstruction of PCL with invasive mini-plate has advantages in the operated field exposure, adequate tibial and femoral fixation and excellent results in motion, stability and function of the knee after the operation. PMID- 11778193 TI - [Testing for isometry during reconstruction of the posterior cruciate ligament]. AB - OBJECTIVE: To measure the isometric point of the attachment site in femur during the reconstruction of posterior cruciate ligament (PCL). METHODS: Seven fresh knee specimens from cadavers were adopted in this experiment. The anterior, posterior, proximal, distal and central points of the PCL's femoral attachment site were respectively anchored to the middle of the PCL's tibial attachment site by the trial isometer wires. The length changes of the intra-articular part of the wires were recorded while the knee was flexed from 0 degree to 120 degrees by a continuous passive motion(CPM) machine. RESULTS: The maximal length changes in every points were compared. It showed that the length change in anterior point was the biggest, the distal point was less than that of anterior point, and the proximal point was the least. There was significant difference between proximal and posterior points, but no significant difference between proximal and central points, neither between central and posterior points. All of the maximal length changes of proximal, central and posterior points were not greater than 2 mm. CONCLUSION: The femoral tunnel for the PCL reconstruction should be located at the proximal point, which is the middle point of upper edge of femoral attachment site. The selected point for femoral tunnel also may be moved slightly in the direction to central or posterior points according to the needs of operation. PMID- 11778194 TI - [Reconstruction of anterior cruciate ligament by free autograft of middle one third of bone-patellar tendon-bone complex]. AB - OBJECTIVE: To investigate the outcome of anterior cruciate ligament (ACL) by free autograft of middle one third of bone-patellar tendon-bone complex which was formed by lower edge of patella, middle one third of patellar tendon, and tibial tubercle. METHODS: From April 1994 to August 1996, ACL reconstruction by bone patellar tendon-bone complex was performed in 8 patients with ACL injury. RESULTS: All cases were followed up 5 months to 3 years, averaged 26 months, excellent results were obtained in 4 cases, better in 3 cases and moderate in 1 case. The Lanchman test and/or anterior drawer test were positive in 8 cases preoperatively and only 1 case was positive postoperatively. Instability existed in 5 cases preoperatively were disappeared after operation. All patients could basically meet the demands of daily life. CONCLUSION: Reconstruction of ACL by free autograft of middle one third of bone-patellar tendon-bone complex is an effective method for the restoration of stability in knee joint. PMID- 11778196 TI - [Experimental study of effect of meniscus suture on meniscus healing]. AB - OBJECTIVE: To investigate the effect of meniscus suture on meniscus healing which included healing time and healing pattern. METHODS: Fourty healthy rabbits were adopted in this study. The model of meniscus injury was made by a longitudinal incision at the medial meniscus of the left knee. The rabbits were divided into two groups, the experimental group was treated by meniscus suture and the control group was unsutured. After operation, the meniscus samples were collected periodically and observed by gross, light and electronic microscope to analysis the meniscus healing. RESULTS: The injured meniscus was healed gradually and completely at the sixth week in the experimental groups. More fibroblasts and less fibrocartilage cells could be observed in the healed meniscus. Oppositely, there was no meniscus healing in the control group and the edge of injured meniscus was sealed by epithelioid cells. CONCLUSION: The meniscus suture can accelerate the healing process of meniscus injury. Besides, early suture make the injured meniscus correctly positioned to ensure the normal healing process. PMID- 11778195 TI - [Primary repair of cartilage defect accompanying patellar fracture with free auto periosteal graft]. AB - OBJECTIVE: To evaluate the results of free auto-periosteal graft in primary repair of cartilage defect accompanying severe comminuted fractured of patella. METHODS: From January 1992 to August 1998, seventeen cases with extensive cartilage defect due to severe comminuted fracture of patella were primarily repaired with free auto-periosteal graft. In these cases, there were whole patellar fracture in 9 patients, upper two third patellar fracture in 3 patients and lower two third patellar fracture in 5 patients. During operation, "S"-shaped incision along medial side of knee through intra-cavity pathway were used. After fixation of the patellar fracture and clearance of the residual cartilage in the fracture area, the cancellous bone was exposed and trimmed. The free periosteum was incised from the anterior medial side of upper tibia and then transplanted to the region of cartilage defect. The size of grafted periosteum ranged from 3 cm x 4 cm 5 cm 6 x cm. The knee joint was received passive motion at 7 days after operation. RESULTS: All cases were followed up 8 to 74 months. There were excellent recovery in 12 patients and the function of knee joint was normal, better recovery in 4 patients and the function of knee joint was nearly normal, and moderate recovery in 1 patient and the function of knee joint was limited mildly. CONCLUSION: Free auto-periosteal graft is a simple and effective treatment in primary repair of cartilage defect accompanying patellar fracture. It is valuable to apply in clinical practice. PMID- 11778197 TI - [Clinical study on chitosan for prevention of elbow adhesion]. AB - OBJECTIVE: To study the clinical effect of chitosan on prevention of elbow adhesion after elbow arthrolysis. METHODS: Twenty six patients with elbow ankylosis were performed elbow arthrolysis, which divided into two groups, in chitosan group, 12 patients were injected 2% chitosan into the elbow joint cavity, and no chitosan used in the other 14 patients as control group. The average range of extension and flexion of elbow joint was detected to evaluate the clinical results. RESULTS: All patients were followed up 8 to 51 months, averaged 24 months. In the chitosan group, the average range of extension and flexion of elbow joint was restored to 92.9 degrees +/- 20.9 degrees, with an average increase of 55.0 degrees +/- 15.9 degrees compared with preoperation. In the control group, the average range of extension and flexion of elbow joint was restored to 75.4 degrees +/- 17.5 degrees, with an average increase of 38.2 degrees +/- 11.9 degrees. The outcome showed significant difference between the chitosan group and the control group (P < 0.01). CONCLUSION: Chitosan can prevent or reduce elbow adhesion after elbow arthrolysis. PMID- 11778198 TI - [Gluteal sciatic nerve injury and its treatment]. AB - OBJECTIVE: To analysis the clinical characters of gluteal sciatic nerve injuries and investigate the treatment options. METHODS: From October 1962 to June 1997, 190 patients with gluteal sciatic nerve injuries were adopted in this retrospective study. In these cases, the sciatic nerve injuries were caused by injection in 164 patients(86.32%), stab injury in 14 patients, pelvic fracture and hip dislocation in 11 patients, and contusion injury in 1 patient. Among them, 15 cases were treated by conservative method and the other 175 cases were operated. According to the observation during the operations, the injuries were occurred at the region of gluteal muscle in 146 cases, at the region of piriform muscle in 26 cases, and at the region of pelvic cavity in 3 cases. Then neurolysis was performed in 160 cases, epineurial neurorrhaphy in 12 cases and nerve grafting in 2 cases, and nerve exploration but no repair in 1 case. Late stage functional reconstruction of the foot and ankle was carried out in 23 cases. RESULTS: One hundred and fifty-one patients were followed up 8.5 years in average. The occurrence of excellent and good nerve recovery was 56.95% and the occurrence of excellent and good functional reconstruction of late stage was 78.26%. CONCLUSION: The gluteal sciatic nerve injury has since been challenging because of the tremendous difficulty in treatment and the poor outcome. The injury situation at the different region was closely related to the regional anatomy. According to this study, it is advised that the surgical treatment should be carried out actively. Neurolysis should be performed as soon as possible in the cases of injection injury. Epineurial neurorrhaphy should be performed in the cases of nerve rupture. In case of the gluteal sciatic nerve injury which caused by pelvic fracture or hip dislocation, the reduction and decompression is suggested in the early stage, and exploration and nerve repair is indicated in the late stage. The functional reconstruction of foot and ankle should be carried out in the late stage for the improvement of the limb function. PMID- 11778199 TI - [A functional evaluation on peripheral nerve regeneration enhanced by targeted muscular injection of ciliary neurotrophic factor]. AB - OBJECTIVE: To investigate the effects of targeted muscular injection of ciliary neurotrophic factor (CNTF) on the regeneration of injured peripheral nerves. METHODS: The left sciatic nerves of 80 Sprague-Dawley rats were excised to form 6 mm defect and the two ends were bridged by silicone tubes, they were randomly divided into two groups, CNTF group and normal saline (NS) group. The CNTF group was given recombinant human CNTF, 1 mg/kg every other day for 30 days, and the NS group was given equal quantity of normal saline as NS group. The sciatic nerve functional index (SFI), electrophysiological assessment, morphometric analysis of axons, and choleratoxin horseradish peroxidase (CB-HRP) retrograde-labelling were measured postoperatively. RESULTS: The SFI, electrophysiological parameters (nerve conduction velocity, latency and amplitude of compound muscle action potentials), myelinated axons counts, mean axons diameters and myelin sheath thickness, number of CB-HRP labelled ventral horn motor neurons of spinal cord were significantly higher in CNTF group than that of NS group. CONCLUSION: Targeted muscular injection of CNTF can promote the regeneration of peripheral nerve and improve the nerve functional recovery. PMID- 11778200 TI - [Establishment of facial nerve elongation model by string-type loading]. AB - OBJECTIVE: To study the repairing method of facial nerve defect using nerve elongation, and the biomechanical properties of peripheral nerves. METHODS: A novel device for peripheral nerve elongation was designed and manufactured. With the device, facial nerves of rabbits were expanded acutely and chronically by string-type loading. The facial nerves were studied with histological and electrophysiological examinations before and after elongation. RESULTS: There were no considerable necrosis, degeneration, and infection in the facial nerves after elongation. The experimental animals took food normally and their body temperature were stable. Histological examinations showed dispersing Sunderland degree III injury and occasionally broken capillary blood vessels in the acute group, thicker nerve and fibroblasts hyperplasia between nerve bundles in the chronic group. The electromyogram(EMG) of buccal muscle and nerve conductive velocity(NCV) showed the maximal range was (18.7 +/- 2.4)% in the acute group, and (30.8 +/- 2.4)% in the chronic group. CONCLUSION: It suggests that the novel nerve elongation method is feasible, and it can be used to study the nerve elongation basically and clinically. PMID- 11778201 TI - [Treatment of ischemic necrosis of femoral head by focal cleaning and bone graft]. AB - OBJECTIVE: To explore a simple and effective method for the treatment of ischemic necrosis of femoral head. METHODS: The anterior region of hip joint was exposed by anterior hip route, a 1.5 cm x 1.0 cm hole was made at the upper region of the femoral neck just below the head. The necrotic bone and sclerotic bone were completely cleaned by drill and curettage until the fresh cancellous bone was exposed. After irrigation, the bone cavity was filled tightly by iliac bone graft until the collapsed femoral head recovered its normal shape. Traction and continuous passive motion(CPM) were performed at the early stage after operation. RESULTS: Twenty cases with 29 femoral head ischemic necrosis (Marcus III to IV stage) were treated by above methods. After 1 to 3 years follow-up, the results were all satisfactory. The pain disappeared, and the functions of the hip joint were all excellent with almost normal walking and squatting. CONCLUSION: The necrotic bone and the sclerotic bone can be removed by this method, thus optimal conditions for the reconstruction of blood supply is obtained. Abundant cancellous bone graft in the residual bone cavity can support the round shape of the femoral head. CPM is very important in the repair of hyaline cartilage and prevention of joint stiffness. It is a simple and effective method in treating femoral head ischemic necrosis. PMID- 11778202 TI - [Treatment of nonunion in childhood by allogeneic decalcified bone graft]. AB - OBJECTIVE: To investigate the effect of allogeneic decalcified bone graft in the treatment of nonunion in children. METHODS: From April 1990 to September 1997, 17 children with nonunion were adopted in this study. Among them, there were 10 boys and 7 girls, the age ranged from 2 to 13 years. The allogeneic decalcified bone graft taken from fresh corpse by aseptic manipulation were used to repair 3 cases of congenital nonunion and 14 cases of acquired nonunion. RESULTS: All cases were followed up 2 to 9 years after operation, 9 cases were cured successfully and 7 cases were cured after twice operations. One case of congenital pseudoarthrosis of the tibia was operated twice and there were callus grown half years after the second operation, but reoccurred after one year. Although there were 1.5 cm to 3 cm shortening deformity of extremity including another 2 cases of congenital pseudoarthrosis of the tibia and 5 cases of nonunion caused by chronic osteomyelitis, the function of joint was normal. CONCLUSION: Treatment of nonunion in children by allogeneic decalcified bone graft is a valuable technique in clinical practice. It is characterised by high capacity of osteoinduction, low antigenicity, rapid bony union, plentiful source of bone graft and convenient utilization. PMID- 11778204 TI - [Strengthen respiratory failure researches]. PMID- 11778203 TI - [Experimental study on prefabricating iliac grafts using composite bone]. AB - OBJECTIVE: To investigate the feasibility of prefabricating a specified shape autograft capable of transfer using coral and type I collagen as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: In this study, the composite of rhBMP-2, coral and type I collagen was made certain shape to prefabricate vascularized osteomuscular autograft capable of microvascular free tissue transfer and autogenous bone graft with certain shape and titanium implant in it. The composite was implanted in the iliac area in dog with the titanium implant at the same time. After 3 months and 4 and a half months of implantation, the composites were studied with gross measurement, X-ray, and histological examinations. RESULTS: After 3 months, composited bone was turned to bone tissue, and the shape of iliac bone was changed with implant in it, bone interface was seen between new bone and implant. And new bone was matured after 4 and a half months. CONCLUSION: Coral and type I collagen are effective carrier for rhBMP-2 to prefabricate vascular osteomuscular autograft with certain shape. The use of rhBMP-2 for tissue engineered microvascular free bone flaps has an unlimited potential and adds a new dimension to maxillofacial reconstruction. PMID- 11778206 TI - [Exploration of improved strategies for mechanical ventilation in COPD]. PMID- 11778205 TI - [Exposition for the diagnosis of acute respiratory distress syndrome]. PMID- 11778207 TI - [Sequential non-invasive following short-term invasive mechanical ventilation in COPD induced hypercapnic respiratory failure]. AB - OBJECTIVE: To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation(MV) in COPD with exacerbated hypercapnic respiratory failure. METHODS: 22 intubated COPD cases with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study. At the time pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis. We call the time as "Pulmonary Infection Control Window", PIC window) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group). Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were used as control group. RESULTS: The groups had similar clinical characteristics and gas exchange, initially and at the time of PIC window. For study group and control group, the duration of invasive MV was (7.1 +/- 2.9) vs (23.0 +/- 14.0) days, P < 0.01; the total duration of ventilatory support was (13 +/- 7) vs (23 +/- 14) days, P < 0.05; the incidence of VAP were 0/11 vs 6/11, P < 0.01; the duration of ICU stay was (13 +/- 7) vs (26 +/- 14) days, P < 0.05, respectively. CONCLUSIONS: In COPD patients requiring intubation and MV for pulmonary infection and hypercapnic respiratory failure, early extubation followed by non-invasive MV initiated at the point of PIC window may significantly decrease the invasive and total durations of ventilatory support, the risk of VAP, and the duration of ICU stay. PMID- 11778208 TI - [Clinical study of weaning predictors in COPD patients with prolonged mechanical ventilation]. AB - OBJECTIVE: To evaluate the combined pulmonary function test at bedside as a predicting parameter of weaning in prolonged mechanically ventilated (MV) patients with chronic obstructive pulmonary disease (COPD). METHODS: 58 patients [mean duration of MV (18.4 +/- 9.2) d] who were divided into two groups were enrolled in this study. Group I included 43 patients [male 30, female 13, mean age (65 +/- 12) y] were successful in weaning, group II included 15 patients [male 10, female 5, mean age (64 +/- 10) y] were failed. ABGs, APACHEII, pulmonary function test and respiratory mechanics were measured in both groups after 30 minutes stable spontaneous breathing. RESULTS: There were no significant difference in ABGs, APACHEII, oxygenation index (OI), dynamic compliance (Cdyn) and airway resistance (Raw) between two groups (all P values > 0.05). There were significant differences in the following parameters between two groups: vital capacity/tidal volume (VC/VT, 2.10 +/- 0.20 vs. 1.30 +/- 0.20), maximal inspiratory pressure (Pimax), (-21 +/- 4) vs. (-13 +/- 3) cm H2O, rapid shallow breath index (RSBI), f/VT, (74 +/- 30) vs. (115 +/- 20) times.min-1.L-1, all P values < 0.05. By the use of VC/VT(> 1.8), Pimax(< -18 cm H2O) and f/VT(< 105 times.min-1.L-1) as the criteria of weaning, the specificity (90%) was significantly higher than each of the above three parameters. CONCLUSION: The bedside combined pulmonary function test (VC/VT, Pimax and f/VT) was a valuable weaning predictor in prolonged mechanically ventilated COPD patients. PMID- 11778209 TI - [Application of pressure volume curve on individual lung-protective ventilation in rabbits with acute lung injury]. AB - OBJECTIVE: To explore the lung-protective effect of ventilation with tidal volume and PEEP determined on pressure-volume curve in oleic acid rabbit models of acute lung injury. METHODS: 24 New Zealand rabbits were randomly divided into 4 groups (V1P1, V1P2, V2P1, V2P2). After inducing lung injury, the P-V curves were measured and drawn. The low and upper inflection point pressure (Pinf and Pdef respectively) were manually determined. Two levels of tidal volume (V1 = 15 ml/kg, V2 reduced for Pplat < Pdef) and two levels of PEEP (P1 = Pinf, P2 = Pinf 3 cm H2O) were selected. The peak airway pressure (PIP), plateau pressure (Pplat), mean pressure (PAW), static compliance (Cst), heart rate, arterial blood pressure and blood-gas analysis were measured. The lung tissues were pathologically analyzed with light microscope. RESULTS: The oxygenation was not significantly different among 4 groups. The reduced VT significantly raised PaCO2 and lowered pH. Larger VT reduced arterial blood pressure. VT and PEEP synergetically raised airway pressure. Larger PEEP improved Cst, which was counteracted by larger VT. Reduced VT significantly lessened alveolar barotrauma. Larger PEEP lightened alveolar hyaline membrane formation and hemorrhage. CONCLUSION: The ventilation with VT and PEEP determined on P-V curve has significant protective effect on the acutely injured lung. PMID- 11778210 TI - [Nasal or oranasal face mask mechanical ventilation in the treatment of acute respiratory distress syndrome]. AB - OBJECTIVE: To Evaluate the effect of nasal or oranasal face mask mechanical ventilation (FMMV) in the treatment of patients with acute respiratory distress syndrome(ARDS). METHODS: 16 ARDS patients were separated into two groups: infection group and non-infection group. The former had 6 cases with pneumonia and 1 case with sepsis; the later had 5 cases with multiple fracture, 2 with operation of intestines obstruction, 1 with operation of spleen rupture, 1 with hepatectomy. In Infection group, the respiratory rate(RR) was (46 +/- 5) times/min, the arterial blood pH 7.49 +/- 0.05, CO2 partial pressure(PaCO2) was (32 +/- 4) mm Hg, and oxygenation index (OI) (144 +/- 23) mm Hg. In non-infection group, the RR, pH, PaCO2, OI was (41 +/- 6) times/min, 7.49 +/- 0.13, (32 +/- 5) mm Hg, (156 +/- 51) mm Hg. All patients were linked with ventilator via nasal or ornasal mask. Pressure support ventilation (PSV) and positive end-expiratory pressure (PEEP) were selected. RESULTS: All patients successfully received FMMV. In infection group, RR and OI returned to (45 +/- 7) times/min (P > 0.05) and (195 +/- 30) mm Hg(P < 0.05) respectively after 2-8 hours via FMMV. But in non infection group, the RR and OI were (35 +/- 4) times/min (P < 0.05) and (228 +/- 90) mm Hg(P < 0.05). 2 cases(29%) in infection group and 8 cases(89%) in non infection were successfully weaned from FMMV. CONCLUSION: FMMV could be as the first choice in ARDS patients without infection, and airway intubation should be given in infectious patients as early as possible. PMID- 11778211 TI - [Proportional assist ventilation: methodology therapeutics on COPD patients compared with pressure support ventilation]. AB - OBJECTIVE: To establish the method for clinical use of proportional assist ventilation (PAV) and evaluate the effect on COPD patients. The main similarities and differences of PAV and pressure support ventilation (PSV) were described. METHODS: 10 ventilated patients of COPD were studied. The elastance and resistance were determined before PAV by both inspiratory-hold technique during a brief period of volume control ventilation and "runaway technique". Either different assist levels of PAV (% assist 80%, 60%, 40%, respectively) or PSV was selected randomly. Values of hemodynamics, blood gas and pulmonary mechanics were monitored. Patients' response was described also. RESULTS: Runaway technique was convenient and reliable. Among different assist percentage no significant difference was found on hemodynamics in stabilized COPD patients. PaO2 was in a good level. Either tidal volume or respiratory rate did not change in a consistent way as the level of assist was decreased. But peak inspiratory pressure was increasing significantly r = 0.928 (P < 0.01) and patients' work of breath had the tendency to decrease (P < 0.05). A significant difference of Borg Category Scale was observed between PAV and PSV [0.50(1.50)] vs [0.75(2.00)], (P < 0.05). No significant difference of hemodynamics was found between the two modes. PaCO2 was significantly higher on PAV than on PSV, 54(24) and 48(23) mm Hg, respectively (P < 0.05). Peak inspiratory pressure on PAV (16 +/- 4) cm H2O was significantly lower than on PSV (21 +/- 3) cm H2O (P < 0.05). CONCLUSIONS: PAV is a feasible method of supporting ventilator-dependent patients that is well tolerated. It can improve breathing pattern and reduce inspiratory effort by decreasing work of breath. PAV can be implemented at much lower peak inspiratory pressure than PSV at the same condition of work of breath by patients. It can also apply proportional pressure support according to patients' ventilatory demand. System that operates according to the theory of PAV is not easy to implement. How to measure elastance and resistance is still a question during the development of PAV. PMID- 11778212 TI - [Analysis of postoperative short-term mortality after lung resection and the corresponding treatment strategies]. AB - OBJECTIVE: To study the risk factors of postoperative short-term mortality after lung resection. METHOD: Retrospective analysis on 46 cases ongoing lung resection but died within 1 month postoperatively. RESULTS: There were 37 males and 9 females in this group, aging 38-74 years old. The mortalities be of the group > or = 60 year-old and below 60 were 1.23% and 0.45% (P < 0.01), respectively. The short-term mortalities of the group of pneumonectomy and partial lung resection were 0.51% and 0.32% (P < 0.01), respectively. Causes of the postoperative death were 17 cases of complications of circulatory system, 10 of cancer metastasis, 10 of acute respiratory failure, 6 of intestinal complications, 2 of bronchopleural fistula and 1 of renal failure. CONCLUSION: Measures such as manuver of perioperative complications and coexistant disorders appropriately, reduction of unnecessary explorative thoracotomy and palliative cancer resection, avoidence of pneumonectomy as possible may be helpful to lower the postoperative short-term mortality. PMID- 11778213 TI - [Assessment of treatment regimens in 58 cases with acute pulmonary embolism]. AB - OBJECTIVE: To explore the best regimen of treatment for acute pulmonary embolism(APE), and to evaluate the efficacy and safety of 2-h infusion of recombinant tissue-type plasminogen activator, Alteplase (rt-PA) and urokinase(UK). METHODS: Fifty-eight patients with APE diagnosed by perfusion lung scanning (ECT) or angiography(CPA) were treated with different regimens: i.e. 2-h infusion of rt-PA or UK (2-h group); low doses of UK for 3-7 days (Qd group); anticoagulants alone and thromboectomy. The results were compared. RESULTS: Of the 41 patients treated with thrombolytic therapy 78% showed improvement in lung perfusion scan and clinical presentation without severe adverse effects, the percentage was significantly higher than that of the anticoagulant group(P < 0.001). The rate of improvement was 84% if thrombolytic therapy was given in 2 h. The mortality rate was lower than anticoagulants and thromboectomy group. The success rate of thromboectomy was 40%. CONCLUSIONS: A 2 h regimen of rt-PA or UK showed reliable efficacy and safety for treatment of APE. The indication of thrombolytic therapy can be extended. Mortality and morbidity could be reduced if thrombolytic therapy followed by anticoagulation is applied as early as possible. PMID- 11778214 TI - [A study on IL-5 and IL-10 in the modulation of asthmatic airway inflammation in murine models]. AB - OBJECTIVE: To observe the time-course profile of airway inflammation in murine asthma model, and to analyze the dynamic profile of pro-inflammatory factor IL-5, and inflammtion-suppressing factor IL-10 in the airway. METHODS: An animal model of asthma was established by OVA sensitizing-challenging BALB/C mice. At seven points (0 h, 8 h, 24 h, 48 h, 96 h, days 7 and days 14) in the time course after challenge, bronchoalveolar lavage (BAL) was performed. Total cell counts, cell differential, eosinophil (EOS) counts and percentages were examined and levels of two Th2 cytokines, IL-5 and IL-10, were detected by ELISA. RESULTS: After OVA challenge, total cell counts, EOS counts and EOS percentages in BALF were increased significantly. EOS count increased at 8 h, formed a plateau from 24 h to 48 h, declined at 96 h, reduced approximately to control from days 7 to days 14. IL-5 in BALF elevated at 8 h, maitained at high level from 28 h to 96 h, decreased at days 7. The dynamic changes of IL-5 was in synchronism with that of EOS counts, a positive correlation being identified. No significant difference was found between IL-10 in BALF before and after challenge. A close correlation between EOS counts and IL-5/IL-10 ratio was demonstrated (r = 0.9, P < 0.001). CONCLUSION: IL-5 and IL-10 up- and down-regulate asthmatic airway inflammation respectively, and their interaction may play an important role in inflammatory progress and resolution. PMID- 11778215 TI - [A study on the changes of calcium signal in mast cells activated by antigen]. AB - OBJECTIVE: To study the relationship between the calcium signal and activation of mast cells, laying the foundation for discovering a new potential theraputical target of signal transduction for type I anaphylactic diseases like asthma. METHODS: The fluorescent Ca2+ indicator Fluo-3 was used to observe and quantitate the calcium signal directly in activated RBL-2H3 mast cells by a flow cytometer and a confocal fluorescence microscope with laser. RESULTS: Antigens elicited significant increase in intracellular Ca2+ concentration ([Ca2+]i) and histamine release in sensitized cells, maximal [Ca2+]i increase being reached (525 +/- 42) nmol/L (n = 12) within 90-110 s after stimulation. Increase of fluo-3 fluorescence intensity was also observed with the confocal fluorescence microscope in cytosol. No significant increase of [Ca2+]i was observed after addition of EDTA in sensitized cells from an initial value of (79 +/- 3) nmol/L, to (80 +/- 4) nmol/L (P > 0.05, n = 12), but tyrosine phosphorylation was readily observed, and the indirect fluorescent intensity was significantly greater than that in the control group. No significant change of [Ca2+]i was observed with the addition of DNP-BSA after PMA (P > 0.05, n = 8). CONCLUSION: Calcium is involved in the activation process of mast cells stimulated by antigens. PMID- 11778216 TI - [Development of DNA vaccines tuberculosis]. PMID- 11778217 TI - [Nontuberculous mycobacteriosis should not be neglected]. PMID- 11778218 TI - [Clinical and pathological analysis of 114 patients with postoperative wound infections by M. abscessus]. AB - OBJECTIVE: To evaluate the pathological findings of postoperative wound infections by M. abscessus. METHODS: Proven sources of infections in 114 patients with postoperative wound infections were contaminated instrument disinfection liquid. According to the wound exudates cultivation and bacteriologic identification, the pathogen of postoperative infections was proved M. abscessus. Pathological features of postoperative wound infections were analyzed retrospectively. RESULTS: The postoperative wound infections in 114 cases involved cutaneous and subcutaneous tissue 95(83.3%), deep muscular tissue 21(18.4%), local lymph nodes 13(11.4%) and visceral organ, peritoneum and mesentery 3(2.6%). The main pathological appearances were granulomatous lesions and nonspecific chronic pyogenic inflammations. The granulomatous lesions include pyogenic tuberculosis-like granuloma, atypical tuberculosis-like granuloma and tuberculosis-like granuloma. The three types of granuloma could be seen in the same case and the percentage of three types was 75.4%, 28.1%, 59.6% respectively. 38 cases (33.3%) were showed red mycobacterium at acid-fast stain. CONCLUSIONS: The pathological appearances of most postoperative wound infections by M. abscessus were more or less different from those of tuberculosis. Awareness of the pathologic features of the postoperative wound M. abscessus infections will facilitate the diagnosis so that appropriate therapy may be initiated before the disease is far advanced and prevent infection dissemination. PMID- 11778219 TI - [Detection of DNA extracted from Mycobacterium tuberculosis by TaqMan-PCR technique and its clinical application]. AB - OBJECTIVE: To evaluate the clinical diagnostic value of TaqMan-PCR technique in the diagnosis of active pulmonary tuberculosis. METHODS: The specimens of sputum and peripheral blood from 168 patients with active pulmonary tuberculosis, 57 patients with lung cancer and the specimens of peripheral blood from 34 healthy individuals were detected by TaqMan-PCR, PCR. The specimens of sputum were also detected by smear, culture with BACTEC and Lowenstein-Jensen for comparison. RESULTS: The positive rates of sputum and peripheral blood detected by TaqMan-PCR were 53.0% and 61.3%, respectively, significantly higher than those of PCR, smear, culture with BACTEC and Lowenstein-Jensen (P < 0.05). There was no significant difference between TaqMan-PCR and PCR for specificity (P > 0.05). Of 105 specimens of peripheral blood from patients with smear-negative and culture negative pulmonary tuberculosis, 48 specimens of peripheral blood detected by TaqMan-PCR were positive. The positive rate was 45.7%. CONCLUSIONS: TaqMan-PCR method showed higher sensitivity and specificity. It is an useful tool for diagnosis of pulmonary tuberculosis, particularly smear-negative and culture negative pulmonary tuberculosis. PMID- 11778220 TI - [The acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats]. AB - OBJECTIVE: To investigate the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and its selective role on pulmonary circulation. METHODS: Tet pulmonary targeting microspheres were synthesized by spraying desiccation, the content of tetrandrine in pulmonary targeting microspheres is 32%. Twenty Wistar rats were exposed to hypoxia for three weeks, the rats were given Tet pulmonary targeting microspheres and Tet aqueous solution respectively and another 10 rats were as normal control. The mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, mean systemic blood pressure (mSBP) was measured by left femoral catheterization. RESULTS: At the end of hypoxic treatment, rats developed pulmonary hypertension. mPAP in the rats receiving Tet pulmonary targeting microspheres decreased more obviously than the rats receiving Tet aqueous solution (P < 0.05), and the effects maintained for 60 min after administration. However, the mSBP remained normal in rats receiving Tet pulmonary targeting microspheres. CONCLUSION: Tet pulmonary targeting microspheres can improve the effect of Tet on the hypoxic pulmonary hypertension and Tet has the selective role on the pulmonary circulation. PMID- 11778221 TI - [Preliminary investigation of effect of serum leptin on nutritional state of COPD patients]. AB - OBJECTIVE: To explore the significance of serum leptin and TNF-alpha in malnutrition of COPD. METHODS: Serum leptin and TNF-alpha concentrations were measured by radioimmunoassay. Body mass index (BMI), percent normal body weight (NW%), triceps skin-fold thickness (TSF), subscapular skin-fold thickness (SSF), mid-upper arm circumference (MAC), serum albumin (ALB) and total lymphocytes count (LYM) were determined in 31 patients with COPD and in 11 healthy controls. The correlation between leptin and nutritional parameters was analysed. RESULTS: (1) Serum leptin concentrations (3.0 +/- 2.5) micrograms/L in 42 subjects were significantly correlated with BMI, NW%, TSF, SSF and MAC (P < 0.001). (2) Serum leptin concentrations were significantly correlated with BMI in both malnourished patients with COPD and non-malnourished patients (P < 0.05-0.001). The leptin level was significantly lower in malnourished group (1.3 +/- 1.0) micrograms/L than in non-malnourished group (4.5 +/- 2.6) micrograms/L, (P < 0.05). The differences in serum leptin level and BMI between non-malnourished group and healthy group were not significant. (3) Serum TNF-alpha level was significantly higher in COPD group (1.8 +/- 0.3) micrograms/L than in healthy group (1.0 +/- 0.5) microgram/L (P < 0.05). Serum leptin levels didn't significantly correlate with TNF-alpha levels in COPD patients. CONCLUSION: Serum leptin levels correlate with nutritional parameters in COPD patients and leptin may contribute to the malnutrition in COPD patients. PMID- 11778222 TI - [Proinflammatory cytokine stimulated NF-kappa B activation and the effect of dexamethasone in the human airway epithelial cells]. AB - OBJECTIVE: To observe the expression of NF-kappa B activation and the effect of dexamethasone on the NF-kappa B activity in the human airway epithelial cell line 16HBE after TNF-alpha stimulation. METHODS: After 16HBE was treated with different concentration of TNF-alpha(10 U/ml, 100 U/ml, 1,000 U/ml) and dexamethasone (100 nmol/L), total RNA and cellular, nuclear protein were extracted at 1 hour, 2 hour, 4 hour, respectively. RT-PCR and electrophoresis mobility shift assay(EMSA) were used to detect the expression of IL-8 mRNA and NF kappa B activation. RESULTS: The activity of NF-kappa B activation became stronger at 1 hour in the TNF-alpha stimulated group than the control, peaked at 2 hours and then decreased at 4 hours. Supershift assay confirmed that both p50 and p65 were components of active NF-kappa B. At the same time, IL-8 mRNA expression was elevated at 4 hours. After dexamethasone treatment, the expression of NF-kappa B activation and IL-8 mRNA became lower. CONCLUSIONS: It is suggested that activated NF-kappa B played a key role in the inflammatory process of respiratory diseases through regulating the expression of some important factors (cytokines). Glucocorticoid inhibited the activation of NF-kappa B and showed antiinflammatory effect. PMID- 11778223 TI - [Observation of biofilms inside tracheal tubes by electron microscopy and the relationship between biofilms and VAP]. AB - OBJECTIVE: To observe the formation of biofilms inside tracheal tubes and to evaluate the effect of biofilm on the development of ventilator associated pneumonia (VAP). METHODS: Biofilms inside tracheal tubes from intubated patients were observed by scanning electron microscopy and transmission electron microscopy, meanwhile bacteria were detected in the specimens from the lower respiratory tract and the inside of tracheal tubes. RESULTS: 76% (19/25) of inner surface of tracheal tubes was coated with a confluent amorphous matrix by scanning electron microscopy. The average duration of trach-intubation in this group [(10.7 +/- 7.9) days] was longer than that in the other group [(2.1 +/- 0.8) days] in which tracheal tubes were not coated with the confluent amorphous matrix (P < 0.05). The presence of many bacteria(14/18) within these amorphous matrix was confirmed by transmission electron microscopy. Of the sixteen tracheal tubes, eleven tubes grew the same organisms that had been isolated from the secretions of the lower respiratory tract before extubation. In some VAP patients (7/8), organisms isolated from tracheal tubes were the same organisms which were pathogenic organisms of VAP. CONCLUSIONS: There was a close connection between the formation of bacterial BF and the long-term indwelling tracheal tubes. The presence of bacterial BF in the inner of tracheal tubes might be associated with the pathogenic organisms of VAP. PMID- 11778224 TI - [Research on drug-resistant gene of nontuberculous mycobacteria]. PMID- 11778225 TI - [Diagnosis and treatment of bronchial tuberculosis]. PMID- 11778227 TI - [Reversion of multidrug resistance in vitro of lung adenocarcinoma by mdr1 ribozyme]. AB - OBJECTIVE: To investigate the possibility of reversion of multidrug resistant (MDR) in lung adenocarcinoma-resistant cell line A549/R by mdr1 ribozyme. METHODS: With GUC at 880 site of mdr1 mRNA selected as target point, plasmid expressing mdr1 ribozyme (pH beta Apr-1 neo/mdr1-Rb) was transduced to A549/R by lipofectin. The expression of mdr1 mRNA and Pgp, cellular rhodamine accumulation and sensitivity to doxorubicin were examined in ribozyme transduced and non transduced cells. RESULTS: Transduction of mdr1 ribozyme to A549/R cells led to decrease in mdr1 mRNA and Pgp expression; increase in rhodamine accumulation. The sensitivity of the ribozyme transduced cells to doxorubicin was 200-fold as high as that of the parental drug-resistant cells. CONCLUSION: MDR of lung adenocarcinoma-resistant cell line A549/R can be effectively reversed with mdr1 ribozyme by cleavage of mdr1 mRNA and inhibition of Pgp expression. PMID- 11778226 TI - [Synthesis of chimeric anti-MDR1 ribozymes (tRNA-Rzs) and their biological activities in cell-free system]. AB - OBJECTIVE: Development of multidrug resistance(MDR) is the major obstacle to successful cancer chemotherapy. One strategy to block the P-glycoprotein(P-gp) mediated MDR is to use a ribozyme (Rz) target against MDR1 mRNA. METHODS: Three kinds of anti-MDR1 chimeric hammerhead ribozymes, the first-one cleaving codon 196 of MDR1 mRNA (196MDR1-Rz), the second one, a stem-II base modified (U9-->G9, U13-->A13, G14-->A14, A18-->C18) Rz against codon 196 (196MDR1-sRz) and the third one, the stem-II base modified Rz directed against the -6(-)-4 GUC sequence of the translation initiation site of the MDR1 mRNA (iMDR1-sRz), were synthesized based on the cloned retroviral constructs: N2A + tRNAi(met)-196MDR1-Rz, N2A + tRNAi(met)-196MDR1-sRz, N2A + tRNAi(met)-iMDR1-sRz. RESULTS: In a cell-free system, the chimeric tRNA-sRz molecules were more stable and had more efficient catalytic activities than the corresponding naked Rz molecules. The stem-II base modified Rz molecules were also more stable and efficient in catalytic activities than the unmodified ones. In control, the disabled tRNA-mut-iMDR1-sRz had no cleavage activity. CONCLUSION: Base modification in the Rz's stem-II of ribozyme structure and the development of chimeric tRNA-ribozyme molecules are able to enhance the cleavage efficacy. PMID- 11778228 TI - [The effects of exogenous p16 gene on proliferation and apoptosis of human nasopharyngeal carcinoma cell line CNE-2]. AB - OBJECTIVE: To study the effects of exogenous p16 gene on proliferation and apoptosis of human nasopharyngeal carcinoma cell line CNE-2. METHODS: Exogenous p16 gene was transfected into CNE-2 cells by lipofectin. After G418 selection, we obtained p16 stably expressed NPC cell clones (CNE-2-p16), and compared it with the mock-transfected clones(CNE-2-vect). Cell cycle was determined by flow cytometry, and cell apoptosis was examined by fluorescent (Hoechst) staining and TUNEL. P16 protein and p53 protein were stained immunohistochemically with relevant antibodies. RESULTS: Exogenous p16 gene was successfully expressed by CNE-2 2 cells. The growth of CNE-2-p16 cells was inhibited significantly. In CNE 2-p16 cells, cycle arrest in G1 phase, with decrease in percentage of S phase cells. Apoptotic index of CNE-2-p16 was significantly increased. CNE-2-p16 cells were positive for p53 protein that it was negative in CNE-2 cells. CONCLUSION: Exogenous p16 inhibits proliferation and induces apoptosis of human nasopharyngeal cancer CNE-2 cell line. It may be related to the up-regulation of wild type p53 gene. PMID- 11778229 TI - [Mechanism of retinoic acid receptor alpha-mediated growth inhibition of gastric cancer cells by all-trans retinoic acid]. AB - OBJECTIVE: To study the mechanism of retinoic acid receptor alpha(RAR alpha) in mediating growth inhibition of gastric cancer cells by all-trans retinoic acid(ATRA). METHODS: Expression of RAR alpha was detected by Northern blot. After anti-sense RAR alpha or sense RAR alpha had been transfected into gastric cancer cell lines BGC-823 and MKN-45 respectively, the inhibitory effect of ATRA on cell growth in stable clones was analyzed using MTT assay and colony forming assay in soft agar. The transcriptional activation of retinoic acid response element (RARE) was measured by CAT assay. RESULTS: ATRA could induce expression of RAR alpha in BGC-823 cells, but not in MKN-45 cells. In stable clones, ATRA could inhibit growth of MKN-45 cells transfected with RAR alpha gene, but could not inhibit that of BGC-823 cells transfected with antisense RAR alpha. Transient transfection and CAT assay showed higher beta-RAR response element (beta RARE) transcriptional activation induced by ATRA in MKN-45 cells transfected with RAR alpha compared to parental MKN-45 cells, while lower beta RARE transcriptional activation was seen in BGC cells transfected with antisense RAR alpha gene compared to parental BGC-823 cells. CONCLUSION: Sufficient level of RAR alpha is required for growth inhibition of gastric cancer cells by ATRA. PMID- 11778230 TI - [Expression in E. coli of protein encoded by human esophageal cancer related gene 1]. AB - OBJECTIVE: To express esophageal cancer related gene-1 (ECRG-1)--in E. coli. METHODS: The human ECRG-1 was cloned by RT-PCR. Expression plasmid of the ECRG 1/GST pi fusion gene was constructed and introduced into E. Coli. The fusion protein was induced to express by ITPG. The recombinant protein was identified by Western blot. BALB/C mice were immunized with the protein purified by SDS-PAGE for the preparation of polyclonal antibody. RESULTS: DNA sequencing confirmed that the sequence of ECRG-1 was identical to that of the previously obtained by 5'-RACE technique. Expression of the protein in E. coli was verified by Western blot. The polyclonal antibody obtained from immunized BALB/C mice had a title of 1:3,200. CONCLUSION: The antibody available is useful for the further study of structure and function of the esophageal cancer related protein. PMID- 11778231 TI - [Comparative study of metastasis-associated characteristics of tumor cells with different metastatic capacities]. AB - OBJECTIVE: To investigate the relationship between metastatic potential and other biological properties of tumor cells. METHODS: Three human colon carcinoma cell lines WiDr, HT-29 and HT-29b with similar genetic background were hetero transplanted into nude rats by mesenteric intravenous inoculation and their dissemination was observed. Homotypic aggregation, target organ colonization, cell proliferation and apoptosis, expression of c-erbB-2, EGFR, p53 and mucin, CA19-9 and CEA of tumor cells of these 3 cell lines were comparatively studied by using three dimensional spheroid cell culture, TUNEL and immunocytochemistry. RESULTS: The three cell lines differed significantly in their metastatic capacities. HT29b and HT29 cells metastasized to the liver, lungs and other parts of the body but the metastasis was more marked in the former than in the latter. WiDr cells did not metastasize at all. In 50%-60% of nude rats with HT-29 and HT29b xenografts, tumor cells were colonized in the liver while no such colonization was seen in rats with WiDr xenograft. The metastatic potential was found to be negatively correlated with the in vitro homotypic aggregating capacity of the tumor cells. The tumor cells with high metastatic potential were found to have higher cell proliferation index but lower cell apoptosis index as compared to those with low metastatic potential. Higher expression of EGFR and mutant p53 in tumor cells with high than in those with low metastatic potential was also observed. No such difference existed in the expression of mucin, CA19-9 and CEA. CONCLUSION: The metastatic capacity of colon carcinoma is associated with such biological properties of tumor cells as homotypic adhesion, target organ colonization, status of cell proliferation and apoptosis, and expression of EGFR and mutant p53. PMID- 11778232 TI - [Modulating effect of vitamin D3 in vitro on EGFR mRNA expression of human breast cancer cell lines]. AB - OBJECTIVE: To assess the modulating effects of vitamin D3, combined with or without tamoxifen, on cell proliferation and EGFR mRNA level of human breast cancer. METHODS: Two breast cancer cell lines (MCF-7 and ZR-75-1) were treated with various concentrations of vitamin D3, alone or in combination with tamoxifen, for 6 days. Cell proliferation was assessed by MIT uptake and EGFR mRNA level by Northern blot. RESULTS: 10(-10)-10(-7) mol/L vitamin D3 strongly inhibited proliferation of the 2 breast cancer lines, while 10(-9)-10(-7) mol/L tamoxifen stimulated proliferation of MCF-7 cell. The growth inhibitory effect on the 2 cell lines could be augmented and accompanied by a decrease in EGFR mRNA level after combined treatment with IC50 dose of tamoxifen and 10(-10)-10(-9) mol/L vitamin D3. CONCLUSION: Vitamin D3 can be considered as a useful anti-tumor drug in the treatment of breast cancer. PMID- 11778233 TI - [The mechanism of docetaxel-induced apoptosis in human lung cancer cells]. AB - OBJECTIVE: To study the mechanism of docetaxel-induced apoptosis. METHODS: Morphological study, DNA gel electrophoresis, flow cytometry and fluorescin labeled Annexin V to detect apoptosis, RT-PCR to detect the gene related with apoptosis. RESULTS: Human lung cancer A549 cells treated with docetaxel induced cell cycle arrest at G2M phase, leading to apoptosis. The morphology of A549 showed nuclear chromatine condensation and fragmentation. Typical ladder pattern of DNA fragmentation was observed. Sub-G1 peak was found by flow cytometry. Transcription of Fas gene was enhanced, while no change in c-myc and bcl-2 genes. Annexin labeling results revealed the co-existence of cell apoptosis and necrosis in docetaxel-treated A549 cells. CONCLUSION: Docetaxel induces apoptosis and necrosis of human lung cancer. The induction of apoptosis may be related to expression of Fas. PMID- 11778234 TI - [Clinical significance of ProGRP31-98 in patients with small-cell lung cancer]. AB - OBJECTIVE: To determine the clinical significance of serum level of pro-gastrin releasing peptide 31-98 (ProGRP31-98) for small-cell lung cancer (SCLC) in comparison with neuron-specific enolase (NSE). METHODS: Serum level of ProGRP31 98 was measured by ELISa in 30 patients with SCLC, 30 patients with non-small cell lung cancer (NSCLC), 10 patients with SCLC who had received treatment, 15 patients with benign lung diseases and 15 normal subjects. The receiver operating characteristic (ROC) curve was used to set the cut-off value and evaluate the diagnostic accuracy. RESULTS: The serum level of ProGRP31-98 was significantly increased in patients with SCLC as compared to that of the normal controls as well as that in any other groups of patients. It was higher in SCLC patients with extensive disease than in patients with limited disease. In patients with distant metastases, it was also higher than in those without. Increase in serum ProGRP31 98 and NSE was both seen in SCLC patients, but the former was of much greater magnitude when compared to the normal controls. Given the cut-off levels of 40 pg/ml for ProGRP31-98 and 8 micrograms/L for NSE, their sensitivity of diagnosis in SCLC was 73% and 60%, respectively. The area under ROC curve of ProGRP31-98 was significantly larger than that of NSE. Similar results of diagnostic sensitivity and area under ROC curve were observed in SCLC patients with limited disease. All patients responded to chemotherapy showed marked decrease in ProGRP31-98. CONCLUSION: ProGRP31-98 is a more specific and sensitive marker than NSE for the diagnosis of SCLC. PMID- 11778235 TI - [The significance of CD3/MIB1 and CD3/CD25 in B cell lymphomas]. AB - OBJECTIVE: To identify the distribution and significance of proliferating T cells (PTC) in normal tonsil and a group of B cell lymphomas. METHODS: Double immunohistochemical staining was used to detect PTC with MIB1 expression. Giemsa staining was used to detect Helicobacter pylori (Hp) in gastric MALT-type lymphoma. Cell culture was applied to investigate the relationship among tumor cells, Hp and T cells. RESULTS: Very few T cells expressed MIB1 in the follicular centre of normal tonsil and in that of follicular lymphoma. PTC were mainly distributed to the extrafollicular and T cell zones. So did CD3+ T cells expressed CD25. In low grade primary B cell gastric MALT-type lymphomas, tumor cells proliferated in vitro in response to Hp but died in the absence of T cells. PTC increased with increase in the degree of malignancy in different kinds of B cell lymphomas. CONCLUSION: T cells in follicular centres of follicular lymphoma are not in cell cycle. Proliferation of neoplastic B cells in low grade gastric MALT-type lymphomas requires Hp-specific infiltrating T cells. Transformation from low to high grade lymphoma is associated with an increase in T cell activation. T cells expressing MIB1 might be related to prognosis. PMID- 11778236 TI - [Detection and significance of lymph node micrometastases in patients with histologically node-negative gastric carcinoma]. AB - OBJECTIVE: To study micrometastasis in lymph nodes from patients with node negative gastric carcinoma according to routine histologic examination and its relevance to prognosis. METHODS: A total of 1,245 perigastric lymph nodes histologically free of metastasis from 105 patients were immunohistochemically stained with monoclonal antibody AE1 against low molecular weight cytokeratin for micrometastases. RESULTS: Micrometastases were observed in 81 lymph nodes(6.5%) of 31 patients (29.5%). The incidence of lymph node micrometastases was significantly higher in the diffuse type(22 of 53 cases, 41.5%) than in the intestinal type of gastric carcinoma (9 of 51 cases, 17.6%, P < 0.01). The presence of micrometastases was closely correlated with the size and invasion depth of primary tumor, but was not correlated with age, sex and location of the primary tumor. The 5-year survival rate after surgery was 61.3% and 82.4%, respectively in patients with and without micrometastases (P = 0.0116). When the number of lymph node with micrometastases was > or = 3, the 5-year survival rate significantly decreased. CONCLUSION: The detection of lymph node micrometastases is necessary to more accurately determine the clinical staging and prognosis of patients with node-negative gastric carcinoma by routine histologic examination. PMID- 11778237 TI - [Chemotherapy of non-small-cell lung cancer (NSCLC) and changes in serum sAPO 1/Fas and nitric oxide (NO) levels]. AB - OBJECTIVE: To investigate the therapeutic efficacy, toxic side effects, and changes in serum level of sAPO-1/Fas and nitric oxide(NO) in NSCLC patients treated with VM-26, epirubicin (EPI) and cisplatin (VED regimen). METHODS: Forty two cases of advanced NSCLC patients (squamous-cell carcinoma, 28; adenocarcinoma, 12; undifferentiated cancer, 2) were treated with 2 cycles of VED. Serum sAPO-1/Fas level was determined by ELISA method, and NO level by enzymatic method before and after treatment. RESULTS: The overall response rate was 47.6% (20/42). Serum sAPO-1/Fas level in patients with squamous-cell carcinoma who responded to treatment was significantly lower than that before treatment. The post-chemotherapy serum NO level was significantly higher than that before chemotherapy in responsive patients with squamous-cell cancer as well as in adenocarcinoma. CONCLUSION: Combination chemotherapy with VM-26, EPI and DDP can be useful in the treatment of patients with advanced NSCLC. Serum sAPO 1/Fas and NO levels could be used to monitor treatment effect. PMID- 11778238 TI - [Methylation and expression of the p16 gene in endometrial carcinoma]. AB - OBJECTIVE: To analyse the relationship between methylation status of the 5' CpG island and mRNA expression of the p16 gene in endometrial carcinoma. METHODS: Methylation status of p16 gene was determined by methylation-sensitive restriction enzymes, PCR and p16 mRNA expression was evaluated by RT-PCR in a series of 8 specimens with normal endometrium(NE), 6 with simple and complex hyperplasia(SCH), 6 with atypical hyperplasia (AH) and 38 with endometrial carcinoma(EC). RESULTS: Eight specimens of NE displayed no methylation and showed normal expression of the p16 mRNA. In 1 of the 6 AH and 13 of the 38(34.21%) EC, there was methylation of p16 exon 1; 5 of the 6 SCH showed overexpression of p16 mRNA, 4 of the 6 AH and 27 of the 38 (71.05%) EC exhibited decrease or loss of p16 mRNA expression. CONCLUSION: Hypermethylation of p16 gene is an early event of endometrial carcinogenesis and is associated with the progression of endometrial carcinoma. Hypermethylation is highly correlated with inhibition of p16 gene transcription. PMID- 11778239 TI - [Judgement of gross type and local invasion of advanced gastric carcinoma by spiral computed tomography]. AB - OBJECTIVE: To evaluate the value of spiral computed tomography(sCT) in the judgement of gross type, invasion to serosa and adjacent organs of advanced gastric carcinoma. METHODS: The sCT results of 53 cases of advanced gastric carcinoma undergone gastrectomy were compared with surgical pathologic findings. RESULTS: The accuracy of judging gross type, location and size of gastric carcinoma was 92.5%, 88.7%, 81.1% respectively; 80.5% of serosal invasion was correctly judged by extraluminal fat sign, while 63.4% by serosal contour sign (P < 0.05). Different serosal types could be differentiated by CT features. The accuracy of judging invasion to pancreas, spleen and transverse colon was 87.8%, 87.8%, and 90.2%; and the specificity was 96.7%, 97.0% and 96.7%, respectively. CONCLUSION: Spiral computed tomography is of help in the identification of the gross type, invasion to serosa and adjacent organs of gastric cancer in its stage of progression. PMID- 11778240 TI - [Clinical value of mediastinoscopy in the diagnosis of mediastinal mass: an analysis of 60 cases]. AB - OBJECTIVE: To study the value of mediastinoscopic examination in the accurate diagnosis of mediastinal mass. METHODS: Standard cervical mediastinoscopy (SCM) or extended mediastinoscopy was applied to patients with mediastinal mass on chest CT or MRI, in order to obtain suspicious tissues at peritracheal, retrosternal, subcarinal, or bilateral hilar areas for pathological study. RESULTS: Of 60 cases in this series, 58 got definite pathological diagnoses. Of the 58 cases, 30 were diagnosed as malignancies, accounting for 51.7% of the cases examined. Twenty-eight of the 58 were diagnosed as benign accounting for 48.3% of them. Small-cell undifferentiated carcinoma was the most common type of malignancy, followed by lymphoma, metastatic adenocarcinoma and squamous cell carcinoma in decreasing frequencies. Over one half of the patients with benign lesions were tuberculosis, followed by sarcoidosis. In this series, 93% of the cases received SCM examination. The most common sampling sites were 2R and 4R areas. CONCLUSION: Mediastinoscopy is a valuable procedure which helps clarify diagnosis of mediastinal mass. PMID- 11778241 TI - [Characteristics of lymph node metastasis of squamous cell carcinoma of thoracic esophagus and its clinical significance]. AB - OBJECTIVE: To study the characteristics of lymph node metastases of squamous-cell carcinoma of thoracic esophagus and its influence on patients' prognosis and find reasonable dissecting approaches of lymph nodes. METHODS: To analyse retrospectively the clinical materials of 243 patients who had undergone resection of squamous-cell carcinoma of thoracic esophagus. RESULTS: Lymph node metastases was found in 110 of the 243 treated patients (45.3%). In 3,813 lymph nodes dissected, metastases existed in 400 (10.5%). The cancer cells disseminated upward and downward to lymph nodes along the esophagus. Tumor differentiation and the depth of tumor invasion were factors influencing lymph node metastases, but the length of tumor was not. The 5-year survival rate of the patients with lymph node metastasis was 16.4%, being much lower than that of patients with no lymph node metastasis (51.9%). The numbers of lymph node metastases had little influence on patients' prognosis. CONCLUSION: Because of the different upward and downward spreading of esophageal cancer cells to the lymph nodes, different lymph node dissecting approaches should be taken. The thoracic, and abdominal regional (two fields) lymph nodes dissection could be appropriate to esophageal carcinoma of the lower thoracic segment, and the cervical, thoracic and abdominal (three fields) lymph node dissection should be done for patients with earlier esophageal carcinoma of upper or middle thoracic segments. PMID- 11778242 TI - [The number of lymph node with metastases influences survival in patients with cancer of the thoracic esophagus]. AB - OBJECTIVE: To study the extent of lymph node involvement in relation to survival of patients with thoracic esophageal carcinoma. METHODS: From 1990 to 1993, there were 112 patients with thoracic esophageal carcinoma undergone esophagectomy through right thoracotomy and three-field lymphadenectomy. They were classified into three groups: group A, 44 patients without lymph node involvement; group B, 36 patients with 1 to 3 positive nodes; group C, 32 patients with > or = 4 involved lymph nodes. Nine possible factors influencing survival were studied. A multivariate analysis of these variables was performed using the cumulative survival rate by the computer's Cox proportional hazard model. RESULTS: The over all cumulative survival rate was 58.4% at 5 years. That for patients in group A, B and C was 88.4%, 50.8% and 20.8%, respectively. Apart from the extent of lymph node metastases, depth of tumor invasion, location and differentiation of tumor were of prognostic significance. CONCLUSION: Lymph node metastasis is the major factor affecting survival of patients with cancer of the thoracic esophagus. PMID- 11778243 TI - [Comparison of several therapeutic methods for hepatocellular carcinoma with tumor thrombi in portal vein]. AB - OBJECTIVE: To compare the therapeutic effect and significance of different treatment methods for hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT). METHODS: One hundred and forty-seven HCC patients with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups. A, conservative treatment group (n = 18); B, hepatic artery ligation (HAL) and/or hepatic artery infusion (HAI) group (n = 18), periodically received postoperative chemoembolizations; C, excision of HCC with removal of PVTT group (n = 79); D, transcatheter hepatic arterial chemoembolization or portal vein infusion (PVI) or HAI after operation group (n = 32). RESULTS: The median survival period was 2, 5, 12, and 16 months in group A, B, C, D, respectively. Their 1-, 3- and 5-year survival rates was 5.6%, 0 and 0 in group A; 22.2%, 5.6% and 0 in group B; 53.9%, 26.9% and 16.6% in group C; 82.8%, 48.8% and 41.3% in group D, respectively. The survival rates differed significantly between the 4 groups (P < 0.05). CONCLUSION: Resection of cancer with removal of tumor thrombi for HCC with PVTT significantly improves the curative effect and quality of life. Local hepatic chemotherapy or chemoembolization after tumor resection with removal of tumor thrombi may further prolong survival period. PMID- 11778244 TI - [The causes of death in patients with malignant biliary obstruction treated by metallic stent and/or biliary drainage]. AB - OBJECTIVE: To analyze the causes of death in patients with malignant bile duct obstruction treated by metallic stent endoprosthesis and biliary drainage. METHODS: One hundred and seven patients with malignant bile duct obstruction were so treated. Of the 107 patients, 12 (11.2%) died within 30 days after operation. The bile duct obstruction in the 12 cases was due to primary hepatic cancer(n = 4), metastasis of lymph nodes in hepatic hilus(n = 3) and bile duct cancer(n = 5). RESULTS: Five patients died of biliary infections, 4 patients died of hepatic coma, and 2 patients died of cancerous cachexia and 1 patient died of biliary tract hemorrhage. CONCLUSION: The major causes of postoperative death of patients with biliary obstruction treated by metallic stent to support bile duct are biliary infection and hepatic encephalopathy. PMID- 11778245 TI - [Surgical treatment of patients with stage IV a liver carcinoma]. AB - OBJECTIVE: To study the result of surgical treatment of patients with stage IV a primary liver carcinoma (PLC). METHODS: Twenty-seven patients with stage IV a PLC treated in 1989-1998 were retrospectively studied. The patients could be divided into 2 groups: (1) The resected group(19 cases) and (2) cytoreductive group(8 cases). Intra-operative B-ultrasound was used to prevent missing of any tumor nodules. Unresectable residual nodules were treated by ethanol injection. Multidisciplinary treatment was given in the perioperative period. RESULTS: The overall 1-, 2- and 3-year survival rate of the 27 patients was 71.4%, 55.6% and 7.7% respectively. The 1-, 2- and 3-year survival rate of the resected and cytoreductive group of patients was 73.3%, 58.3%, 10.0% and 66.7%, 50.0%, 0% (P > 0.05) respectively. Complications occurred in 22.0% of the treated patients. There was no operative and hospitalization mortality. CONCLUSIONS: Surgical resection or cytoreductive operation with adjuvant therapy is effective as the first choice of treatment for stage IV a PLC. PMID- 11778246 TI - Helping school nurses recognize student behaviors that may indicate PDD and other autism-related syndromes. PMID- 11778247 TI - Updates on students and their perceptions of risk associated with drug use. PMID- 11778248 TI - A school nurse's guide to vision screening and ocular emergencies--Part 3. PMID- 11778249 TI - Pediatric asthma in the school setting. PMID- 11778250 TI - Effective hand washing in an elementary school. PMID- 11778251 TI - Why teens are not getting the health care they need. PMID- 11778252 TI - A review of the Bard "Open Lines" Education Program. AB - Each nephrology professional is impacted by the ever-tightening belt and shrinking budget. One of the many challenges facing us today is having to do more with less, and this will only continue. Not all nephrology programs have educators, which means that resource materials may be scarce if they exist at all. It is very encouraging to see industry work with our professional group to develop programs and tools for both nursing and patient education. This type of collaboration is necessary to provide us with current materials enabling us to provide excellent patient care. PMID- 11778253 TI - Hemodialysis vascular access monitoring for stenosis. AB - A program evaluation of hemodialysis vascular access monitoring was undertaken to determine the effectiveness of serial, objective measurement, running venous dialysis pressures, in reducing access thrombosis in arterio-venous fistulae, as well as to assess the feasibility of long-term, routine monitoring for clients in a limited-care community hemodialysis unit. In all, 102 of 112 eligible patients participated in the study with a 98% compliance rate. Angiography confirmed stenosis in all eight performed for elevated venous pressures and 16 of 20 performed for clinical suspicion. Venous pressure frequency distributions indicated significantly lower venous pressures in lower arm arterio-venous fistulae than in upper arm arteriovenous fistulae or PTFE grafts. Running venous dialysis pressures are effective and feasible for predicting venous stenoses in arteriovenous fistulae in a limited care community hemodialysis unit. Lower and differentiated threshold pressures would increase the sensitivity of this screening tool; the effect on specificity would have to be evaluated. PMID- 11778254 TI - Technicians/technologists face growing demands for professional accountability. AB - As the scope of technical practice continues to advance, technical specialists are impacted by increasing demands on their knowledge and skills. In this article, the author discusses the issues of credentialing for technical specialists and workplace trends that increase professional accountability. A program of studies, endorsed by two professional associations, addresses the educational needs of technical specialists. PMID- 11778255 TI - The pathophysiology and management of renal bone disease in dialysis patients. AB - As renal function declines, changes in mineral metabolism occur including phosphate retention, calcitriol deficiency, and the development of secondary hyperparathyroidism. Renal bone disease related to disordered mineral metabolism may result in increased patient morbidity and mortality. Uncontrolled parathyroid hormone (PTH) secretion will result in osteitis fibrosa, a high turnover bone disease. The use of calcium and aluminum-based phosphate binders and vitamin D sterols may contribute to the development of low turnover bone diseases such as osteomalacia and aplastic bone disease. Prevention and control of renal bone disease is an important goal for the interdisciplinary health care team. This paper discusses disordered mineral metabolism and its relationship to renal bone disease. Case studies illustrate the development and treatment of renal bone disease related to secondary hyperparathyroidism and aluminum intoxication. PMID- 11778256 TI - [Lung volume reduction in treatment of severe obstructive emphysema]. PMID- 11778257 TI - [Evaluation of exercise performance and quality of life after lung volume reduction surgery for severe emphysema]. AB - OBJECTIVE: To evaluate grade of dyspnea, exercise performance and quality of life pre and post-lung volume reduction surgery in patients with severe emphysema. METHODS: Serial measurement of lung function, cardiopulmonary exercise test and 6 minute walk distance, and the dyspnea grade assessment by modified dyspnea scale of English Medical Research Council and quality of life by Notting-ham Health Profile were all done before and at 3, 6, 12 months after surgery. RESULTS: FVC, FEV1, MVV increased (P < 0.01) and RV, TLC, RV/TLC decreased at 3, 6, 12 months after surgery (P < 0.01), WATT, TET, VO2max, VO2max/HR, VEmax, VTmax, 6MWD were all improved (P < 0.01), and the dyspnea grade was declined as well as the NHP score(P < 0.01 or < 0.05). CONCLUSION: Lung volume reduction surgery in patients with severe emphysema may improve patient's exercise performance and quality of life. PMID- 11778258 TI - [Detection and significance of interleukin-8,6, tumor necrosis factor-alpha in sputa from patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To evaluate the role of cytokines in the pathogenesis of COPD. METHODS: Induced sputum samples were obtained from 20 patients with stable COPD, 10 healthy smokers (HS) and 10 healthy nonsmokers (HNS). Total and differential cell counts were examined, and sputum interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, IL-6 level were measured by radioimmunoassay technique. RESULTS: Sputum IL-8, TNF-alpha level and neutrophil percentages (PMN) in the COPD group were significantly higher than those in the HS group and the HNS group (P < 0.01). Compared with the HNS group, there was a significant increase in the PMN and the level of IL-8 in the HS group (P < 0.05). The sputum level of IL-6 did not differ significantly among three groups (P > 0.05). In the COPD group, the sputum level of IL-8 was correlated positively with the level of TNF-alpha and the PMN (r's = 0.5999, 0.6737). In the HS group the sputum level of IL-8 was also correlated positively with the PMN (rs = 0.8424). The sputum IL-8, TNF-alpha levels and the PMN were all correlated negatively with FEV1% and FEV1/FVC in the COPD group (r's = -0.6453, -0.7341, -0.7341, -0.7624, -0.5262, -0.7353). CONCLUSIONS: IL-8, TNF-alpha and neutrophil are involved in airway inflammation which results in airflow obstruction, thus playing an important role in the pathogenetic process of COPD. PMID- 11778260 TI - [Influence of the subglottic secretion drainage on the morbidity of ventilator associated pneumonia in mechanically ventilated patients]. AB - OBJECTIVE: To assess the influence of the subglottic secretion drainage on the morbidity of ventilator associated pneumonia in mechanically ventilated patients. METHODS: All cases requiring intubation in SICU were intubated with a special type endotracheal tube which has a small-bore cannula in its wall for subglottic secretion drainage. They were randomly divided into two groups received subglottic secretion drainage(SSD) and usual care(NON-SSD) respectively. Bacterial culture of samples from the oropharynx, subglottic secretions and lower respiratory tract were obtained periodically. The amount of subglottic secretion aspirated daily, ventilated days and the number of cases with VAP were recorded. Etiologic diagnosis of VAP was based on the quantitative bacterial culture of secretions obtained by protected specimen brush(PSB). RESULTS: The morbidity of VAP in the SSD group (n = 35) (23%) was lower than that in the NON-SSD group (n = 33) (45%) (P < 0.05). The difference was due to the significant reduction of VAP caused by gram-positive cocci and Haemophilus influenzae organisms. However, no difference was observed in the incidence of VAP caused by non-fermental bacteria. After intubation the onset of VAP was delayed in SSD group (14 +/- 8 day) as compared with the NON-SSD group (6 +/- 4 day) (P < 0.05). The same organisms were isolated by PSB among 61% (14/23) patients with VAP as what were previously isolated from the subglottic secretions. CONCLUSIONS: The presence of subglottic secretion may be an origin of the pathogenetic organisms of VAP. The morbidity of VAP in mechanically ventilated patients can be reduced by SSD, especially for VAP caused by gram-positive cocci and Haemophilus influenzae organisms. SSD may be a simple and effective method for prevention of VAP. PMID- 11778259 TI - [The role of granulocyte colony-stimulating factor in pathogenesis of acute lung injury]. AB - OBJECTIVE: To investigate the role of granulocyte colony-stimulating factor (G CSF) in pathogenetic mechanism of acute lung injury (ALI) by endotoxin. METHODS: A rat model of ALI was established by intraperitoneal injection of Escherichia coli LPS with a dose of 2 mg/kg. Thirty SD rats were randomly divided into the normal group and four endotoxin treated groups at different time intervals (2 h, 4 h, 6 h, 8 h after LPS injection), 6 rats each group. RT-PCR method was used to determine the expression level of G-CSF mRNA in lung tissue. The concentrations of serum TNF-alpha were determined by RIA. The number of neutrophils fixed in lung and peripheral blood neutrophils were counted, and pathological changes of lung tissue were examinted. RESULTS: The level of G-CSF mRNA expression in lung tissue increased rapidly at 2 h after LPS injection, peaked at 4 h. Although decreased a little at 6 h and 8 h, it was still significantly different from the normal group and the 2 h group (P < 0.01, P < 0.05). The level of TNF-alpha peaked at 2 h after endotoxin injection, which was significantly different from the normal group (P < 0.05). The number of neutrophils fixed in the lung also increased in endotoxin-treated groups, and the level of G-CSF mRNA expression in the lung tissue was positively correlated with the number of neutrophils fixed in the lung, the lung coefficient and the pathological signs of lung injury. CONCLUSIONS: The increase in the level of G-CSF mRNA expression in the lung tissue after endotoxin injection resulted in neutrophil sequestration in the lung, which may aggravate lung injury and increase lung coefficient. This process may be an important link in the pathogenetic mechanism of ALI induced by endotoxin. PMID- 11778261 TI - [The diagnostic value of telomerase activity in bronchial biopsy specimen for lung cancer]. AB - OBJECTIVE: To explore the diagnostic value of telomerase activity for lung cancer. METHODS: Telomerase activity was measured by PCR-TRAP in cancerous lesions and contralateral bronchial tissues from patients with lung cancer and in the bronchial tissues from patients with noncancerous pulmonary disorders, in which the tissue specimens were obtained by fiberoptic bronchoscopy. The result of telomerase detection was compared with the positive rates of pathologic study and bronchial brush cytology. RESULTS: The positive rate of telomerase activity in lesions of lung cancer was significantly higher than that in tissues of the contralateral bronchi from patients of lung cancer (P < 0.01) and that in tissues from patients of noncancerous pulmonary disorders (P < 0.01). There was no significant difference between the positive rate of telomerase activity expression and the positive rates of pathology and bronchial brush cytology (P > 0.05). CONCLUSION: Examination of telomerase activity was of significance in the diagnosis of lung cancer. PMID- 11778262 TI - [Dendritic cell infiltration in lung adenocarcinoma and its effect on prognosis]. AB - OBJECTIVE: To study the infiltration degree of dendritic cells in lung adenocarcinoma and its effect on prognosis. METHODS: S-100 protein was used as the specific marker for dendritic cells, and immunohistochemistry was employed to detect the distribution of dendritic cells in lung adenocarcinoma. RESULTS: Among 46 cases of lung adenocarcinoma, 19 were markedly infiltrated by dendritic cells, the five-year survival rate being 61%; 27 showed slight infiltration, the five year survival rate being 21%. Among the 46 cases of adenocarcinoma, 26 were low differentiated adenocarcinoma, in which 10 were infiltrated markedly by dendritic cells, five-year survival rate being 57%; and 16 were slightly infiltrated, five year survival rate being 16%. These data were evaluated with the log-rank test, which showed a significant difference between the markedly infiltrated group and the slightly infiltrated group. CONCLUSION: The prognosis of lung adenocarcinoma which markedly infiltrated by dendritic cells is better than that of slightly infiltrated by dendritic cells. PMID- 11778263 TI - [Rapid rifampicin susceptibility test by using recombinant mycobacteriophages]. AB - OBJECTIVE: To set up a fast, sensitive and specific way to detect mycobacteria and rifampicin susceptibility to mycobacteria by using recombinant mycobacteriophages and bioluminescent method. METHODS: Firstly detected the luciferase activity in different bacteria by using mycobacteriophages, then assessed the best drug concentration of rifampicin for drug susceptibility test in luciferase reporter assay, and lastly used the above conditions to decide rifampicin susceptibilities to different mycobacteria and compare the result with L-J medium culture. RESULTS: Bacteriophages had high light production specifically in mycobacteria and only very low light production in E. coli, the difference being obvious. The light production of rifampicin-resisitant mycobacterium strains was much higher than that of sensitive strains in culture with rifampicin(P < 0.05). Different drug concentrations of rifampicin were used to optimize drug concentration for rifampicin drug susceptibility test and the optimum concentration was found to be 2 micrograms/ml. The correlation of drug susceptibility test between luciferase reporter phages to L-J medium in standard strains and clinical isolates was the sarce. Temperature sensitive Phage 88 was more sensitive than Phage 40(P < 0.05). The time for drug resistance test was 72 hours. CONCLUSIONS: Luciferase reporter phage can detect mycobacteria specifically and can be used in rifampicin susceptibility test. This assay is a fast, sensitive and specific method to detect mycobacterium strains and their resistance to rifampicin. PMID- 11778264 TI - [The immunogenic characteristics of the recombinant 38,000 antigen from Mycobacterium tuberculosis]. AB - OBJECTIVE: To study the ability of recombinant 38,000 protein of Mycobacterium tuberculosis (rMT38) to induce antibodies and its value as a serological diagnostic reagent. METHODS: Rabbits were divided into six groups, namely: PPD + physiological saline(group A), rMT38 + physiological saline(group B), rMT38 + adjuvent(group C), 1/2 rMT38 + 1/2 rMT16 + physiological saline(group D), 1/2 rMT38 + 1/2 rMT16 + adjuvent(group E), rMT16 + adjuvent(group F). The sera from the immunized rabbits and the sera immunized by mycobacteria were evaluated by enzyme-linked immunosorbent assay(ELISA) and bilateral agar diffusion assay (BADA). 389 human sera, including 145 patients with pulmonary tuberculosis, 105 healthy controls, 31 non-tuberculosis respiratory patients, 78 BCG-vaccinated healthy controls and 30 patients with M. abscessus infection, were detected by ELISA. RESULTS: Titers of specific antibodies in sera from C and E groups were 1:16 and 1:4 in BADA, and 1:6,400 and 1:3,200 in ELISA, respectively. Precipitate lines of sera from A, B, D, F groups reacting with rMT38 were not found by BADA. Sera titer of A, B, D, F groups were negative, 1:400, 1:400, and negative by ELISA, respectively. Sera from E group had no reaction with PPD from thirteen mycobacteria, however, sera from E group reacted with PPD from Mycobacterium tuberculosis and BCG. Sera titer of all rabbits decreased with time. After two months, serum titers in B and D groups became negative. However, antibodies were still found in C and E groups after five months. The sensitivity of rMT38 and PPD in detecting pulmonary tuberculosis were 69.0% and 75.2%, respectively. The specificity of rMT38 and PPD in detecting healthy controls, non-tuberculosis respiratory patients, BCG-vaccinated healthy controls and M. abscessus-infected patients were 97.1%, 93.5%, 86.0%, 53.6% and 94.3%, 87.1%, 67.9%, 39.3% respectively. CONCLUSION: rMT38 has a strong immunogenicity, which may be used as an immunodiagnostic reagent for tuberculosis. PMID- 11778265 TI - [Water channel and lung fluid transport]. PMID- 11778266 TI - [Bronchogenic carcinoma and antiangiogenic therapy]. PMID- 11778267 TI - [The relationship between sensitivity to arsenic trioxide and antioxidative capacity of malignant hematopoietic cells]. AB - OBJECTIVE: To detect the relationship between sensitivity of malignant hematopoietic cells to arsenic trioxide (As2O3) and cellular capacity against oxidation. METHODS: Nine cell lines derived from hematopoietic malignancies were treated with As2O3 in vitro. Apoptosis was assessed by cellular viability, cytomorphology and flow cytometry. The As2O3-treated cells were examined for glutathione (GSH) level and activity of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione peroxidase (GPX). RESULTS: Of the 9 cell lines examined, the acute promyelocytic leukemia cell line NB4 and its retinoic acid-resistant subclones R2 and MR2, the Burkitt lymphoma cell line Namalwa and multiple myeloma cell line RPMI 8226 were sensitive to As2O3-induced apoptosis while the acute T cell leukemia cell line (Jurkat) and 3 cell lines (HL 60, U937, K562) of myelogenous leukemia origin were not. In comparison with the sensitive cell lines, higher activity of CAT was found in HL-60 and U937, higher level of GSH in Jurkat, and both in K562. However, activity of GPX, GST and SOD did not significantly correlate with their resistance to As2O3-induced apoptosis. CONCLUSION: Intracellular GSH level and/or catalase activity are important factors to determine sensitivity of malignant hematopoietic cells to As2O3 induced apoptosis. PMID- 11778269 TI - [Ligand of platelet and T cell activation antigen 1 (PTA1) expressed on Colo205 cell surface]. AB - OBJECTIVE: To confirm the existence of PTA1 ligand (PTA1L). METHODS: PTA1/Ig fusion protein was prepared by gene recombination and expression in COS-7 cells by DEAE-dextran transfection. The fusion protein was used as a probe in the investigation of PTA1L by immunohistochemical staining. Existence of PTA1L was further identified by adhesion experiment. RESULTS: Colo205 cells could be stained by PTA1/Ig fusion protein specifically but not by hIg, and the adhesion of activated Jurkat cells with Colo205 could be blocked by PTA1/Ig and PTA1 mAb. CONCLUSION: PTA1 ligand is present on the surface of Colo205 cells. These results provide a solid basis for further investigation of the role of PTA1-PTA1L interaction in the pathogenesis of neoplasm. PMID- 11778268 TI - [Genistein exerts multiple suppressive effects on human breast carcinoma cells]. AB - OBJECTIVE: To study the suppressive effects of genistein on progression of breast carcinoma. METHODS: In vitro cell culture, animal studies, zymography, Northern and Western blot were used in this study. RESULTS: Genistein inhibited in vitro invasion of MCF-7 and MDA-MB-231 cells. This inhibition was associated with down regulation of MMP-9 and up-regulation of TIMP-1. These effects were also demonstrated in vivo. Genistein inhibited growth of the breast cancer cells transplanted in nude mice. The growth inhibitory effect was associated with increased tumor cell apoptosis, and up-regulated p21WAF1/CIP1 expression. Furthermore, genistein inhibited angiogenesis as shown by decreased vessel density and decreased production and release of VEGF and TGF-beta 1. CONCLUSION: Genistein exerts multiple suppressive effects on breast carcinoma. It may help halt its progression. PMID- 11778270 TI - [Down regulation of HER2/neu expression by adenovirus E1A and its anti-tumor activity]. AB - OBJECTIVE: To study the growth inhibitory and chemo-sensitizing effects of adenovirus E1A gene on HER2/neu-overexpressing tumor cell lines. METHODS: E1A was transfected in vitro and in vivo by adenovirus vector into HER2/neu overexpressing human mammary cancer cell lines MDA-MB-453 and SKBR3 and their growth was monitored. The chemo-sensitizing effect was examined by MTT assay. RESULTS: E1A greatly inhibited growth of HER2/neu-overexpressing tumor and prolonged the survival time of tumor-bearing mice. Western blot and immunohistochemical analysis both showed suppression of p185 protein expression in E1A-transfected HER2/neu overexpressing cancer cell lines. E1A could sensitize HER2/neu-overexpressing human breast cancer cells to Taxotere by repressing HER2/neu expression. CONCLUSION: Adenovirus E1A inhibits tumor growth and sensitizes tumor cells to chemotherapeutic agent via down regulation of HER2/neu expression. PMID- 11778271 TI - [Effect of adenovirus type 5 E1A gene on proliferation and metastasis of human lung adenocarcinoma cells]. AB - OBJECTIVE: To investigate the effects of E1A gene on proliferation and metastasis of human lung adenocarcinoma cells. METHODS: A mammalian E1A-expressing recombinant constructed in our laboratory, named pcDNA3-E1A, was introduced into human lung adenocarcinoma cell line(Anip 973) by lipofectamine. The cells resistant to G418 were selected. The characteristics of the E1A-expressing Anip 973(Anip 973-E1A) cells were studied in vitro and in vivo, including cell growth rate and doubling-time, colony-forming efficiency on soft agarose, tumorigenicity and metastasis. RESULTS: The growth rate of E1A-Anip 973 cells was diminished and their colony-forming efficiency was inhibited significantly. The tumorigenicity in nude mice of the E1A-expressing Anip 973 was markedly suppressed. CONCLUSION: E1A suppresses the malignant phenotype of human lung adenocarcinoma cell line. This study provides experimental data for gene therapy of lung cancer with E1A. PMID- 11778272 TI - [Analysis on loss of heterozygosity of chromosome 17p13.3 in hepatocellular carcinoma and construction of genomic contig in the deleted region]. AB - OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 17p13.3 in hepatocellular carcinoma (HCC) and determine a minimum region of LOH as well as construct genomic contig in LOH region. METHODS: Variable number tandem repeat (VNTR) and RFLP markers examined by Southern hybridization were used to detect LOH of HCC. Microsatellite markers amplified by PCR were detected for LOH by denatured PAGE. Using microsatellite primers, 3 rounds of PCR amplification were carried out to screen positive genomic clones. The contig was constructed by PCR detecting the reaction between microsatellite markers and individual genomic clone. RESULT: Fifty-four paired HCC samples were analysed with 16 polymorphic markers on chromosome 17p13.3. The data revealed that the region between D17S5 and D17S34 had a high rate of LOH (> 63%), but three markers (proximal to D17S5) toward centromere had low or no LOH. TP53 marker on chromosome 17p13.1 had a LOH rate of 31% which was lower than that on D17S5 D17S34 region. No LOH was found at D17S34, D17S1866 (proximal to telomere) and D17S5, D17S1574 (distal to telomere) in 2 cases of HCC. However, there was LOH between D17S849 and D17S1574 in some cases. In LOH region, genomic clones relative to 18 of markers were obtained. A contig covering 9 markers was constructed. CONCLUSION: Determination of the minimum LOH region on chromosome 17p13.3 in HCC and the construction of genomic clone contig provide basis for further identification of putative new tumor suppressor gene(s) in HCC. PMID- 11778273 TI - [Effect of nm23H1 on proliferation, tumor formation and metastasis of hepatocarcinoma]. AB - OBJECTIVE: To study the effects of nm23H1 on in vitro proliferation, in vivo tumor formation and metastasis of hepatocarcinoma. METHODS: Vectors containing insert of either sense or antisense nm23H1 cDNA under the albumin enhancer/promoter for liver cell-specific expression were constructed. The expression vectors were transfected into hepatocarcinoma cell line SMMC-7721. Stable cell clones with maximum and minimum expression of nm23 were obtained. Cell growth was measured in vitro and metastasis was observed in vivo by injecting cells into nude mice, subcutaneously or under the spleen capsule. RESULTS: In vitro, cell clone expressing antisense nm23H1 grew faster than that expressing sense nm23H1. In nude mice, the subcutaneously inoculated tumor grew faster and more aggressively in mice bearing antisense nm23H1 transfected hepatoma. So did metastasis of the antisense nm23H1 transfected hepatoma under the spleen capsule. CONCLUSION: Apart from suppressing metastasis, nm23H1 significantly suppresses tumor cell proliferation in vitro and tumor growth in vivo. PMID- 11778274 TI - [Development of drug resistance and alteration of cell cycle in lung cancer: a flow cytometric study]. AB - OBJECTIVE: To study the relationship between the expression of multidrug resistance-associated protein (MRP) and P-glycoprotein (P-gp) and alteration of cell cycle during the process of drug resistance in lung cancer. METHODS: Lung adenocarcinoma cell line GLC-82 was treated with low concentration of adriamycin. At 0, 24, 48, 72 and 96 hr following adriamycin treatment, the expression of MRP and P-gp, and cell cycle were examined by bi-parameter flow cytometry. RESULTS: Treatment of GLC-82 cells with adriamycin at a final concentration of 0.05 microgram/ml resulted in progressive decrease in cells in G1 phase and increase in cells in S phase of the cell cycle. The expression level of P-gp was very low and showed little change with time. In contrast, MRP expression was significantly increased in a time-dependent manner, and was positively correlated with changes in S phase of the cell cycle. CONCLUSION: MRP expression may play a major role in the development of resistance to adriamycin. PMID- 11778275 TI - [Functional status of p53 and chemosensitivity of colon cancer cell lines]. AB - OBJECTIVE: To study the functional status of tumor suppressor gene p53 in relation to chemotherapeutic sensitivity in colon cancer cell lines. METHODS: With the use of functional assay (FASAY) of p53, the existing p53 status (wt, mt) of 6 colon cancer cell lines was determined. The difference in chemotherapeutic sensitivity of colon cancer cells with wild-type p53 was compared with those with mutated type p53 by MTT method, followed by cytometic analysis of cell cycle. RESULTS: The chemotherapeutic sensitivity of Lovo and LS 174T cancer cell lines with wild-type p53 was 5-10 times higher than that of 4 other cell lines with mutated p53. Selective apoptosis and cell cycle arrest in G1 phase occurred when treated with adriamycin. CONCLUSION: The functional status of p53 in human colon cancer cell lines directly affects their sensitivity to chemotherapeutic agents. PMID- 11778276 TI - [Clinical significance of sentinel lymph node biopsy in breast cancer]. AB - OBJECTIVE: To study the necessity, feasibility, accuracy and clinical value of sentinel lymph node(SLN) biopsy in the management of breast cancer. METHODS: Technetium-99m labeled colloid particles were injected subcutaneously below the breast tumor before mastectomy. The sentinel lymph nodes identified by lymphoscintigraphy and gamma-counter were dissected out from the excised axillary tissue and separately examined manually for consistency and histologically. RESULTS: In 30 cases studied, SLNs were identified in all but one, with a detection rate of 96.7%. Metastases were detected in SLNS in 8 cases. The other case showed positive axillary lymph nodes but SLN was negative. The sensitivity of SLN biopsy in this study was 88.9%, accuracy was 93.3%, false positive was 0, false negative was 11.1%. CONCLUSION: SLN biopsy, though still under investigation, may in the future substitute routine axillary lymph node dissection in the management of breast cancer. PMID- 11778277 TI - [Laser-induced fluorescence (LIF) spectrum of colorectal cancer in vivo]. AB - OBJECTIVE: To study the LIF spectrum of colorectal cancer, adenomas, chronic colitis and normal colon tissue in vivo, with special emphasis on precancerous lesions. METHODS: A nitrogen laser (wavelength 337 nm) beam was introduced through endoscopic colonoscope and the fluorescence emission was recorded. An optical multichannel analyzer (OMA III) was used to analyze the fluorescence emission spectrum. A total of 83 patients was examined. RESULTS: The emission spectrum of LIF recorded on colorectal cancer and normal tissue showed significant differences in intensity and shape. (1) The normal tissue had higher intensity than that of cancer tissue. (2) The main peak wavelength of cancer moved to the red. (3) The minor peak of the cancer tissue fell more slowly than that of the normal tissue. Intensity of the main peak (x1), intensity ratio of 400 to 530 nm (x2) and the integrated LIF intensity (350-600 nm) (x3) were used as parameters to obtain an equation. The sensitivity and specificity of LIF for diagnosis of colorectal cancer was 83.3% and 94.4%, respectively. In 87.1% of moderate and severe dysplastic adenomatous polyps, the fluorescence spectrum was abnormal. CONCLUSION: In vivo, the LIF spectrum can be used to distinguish colorectal cancer from normal colon, especially from dysplasia. It plays an important role in the early diagnosis of colorectal cancer. PMID- 11778278 TI - [Research on the regular pattern of Ag-NOR changes in patients with cancer]. AB - OBJECTIVE: To correlate the relationship between rDNA transcriptional activity of CD4+ helper T cells and immunity in patients with cancer through silver stainability of nucleolus organizing regions (Ag-NORs). METHODS: The Th(CD4+) rDNA transcriptional activity was compared among patients with cancer, infectious diseases, non-cancerous non-infectious diseases through image analysis. RESULTS: Th(CD4+) rDNA transcriptional activity was decreased extremely in patients with cancer, but increased in patients with inflammation compared with normal controls. CONCLUSION: The analysis of Th(CD4+) rDNA transcriptional activity may serve as a new tumor marker for tumor diagnosis and differential diagnosis. Therefore, it may provide an innovative and reliable method for clinical cancer diagnosis. PMID- 11778279 TI - [Clinicopathologic criteria for the diagnosis of extranodal anaplastic large-cell lymphoma: a preliminary study]. AB - OBJECTIVE: To study and observe the clinicopathologic features of extranodal Ki-1 (CD30) positive anaplastic large-cell lymphoma (ALCL) in order to assess its diagnostic criteria. METHODS: Lymph nodes of 12 patients with Ki-1 positive ALCL were examined histopathologically and immunohistochemically. RESULTS: There were distinctive histopathological features of ALCL cells. Immunohistochemical staining revealed that all of the ALCL were Ki-1 positive (CD30 or Ber-H2). Of them, 5 cases were leucocyte common antigen (LCA) and epithelial membrane antigen (EMA) positive, 2 cases were LCA negative and EMA positive, 1 case was LCA positive and EMA negative, and the other 4 cases were both negative. Seven cases (58.3%) showed B cell markers, 2 cases (16.7%) showed T cell markers and remaining 3 cases had neither T nor B markers. CONCLUSION: Extranodal Ki-1 (CD30) positive ALCL has distinctive histopathologic and immunohistochemical features which help its differential diagnosis. PMID- 11778280 TI - [Preliminary clinical comparison of HLF and ELF regimen in the treatment of advanced gastric carcinoma in middle-aged and elderly patients]. AB - OBJECTIVE: To observe the therapeutic effects and toxicity of HLF (hydroxycamptothecin HCPT/leucovorin LV/fluorouracil 5-Fu) regimen and ELF (etoposide VP-16/LV/5-Fu) regimen in middle-aged and elderly patients with advanced gastric carcinoma. METHODS: A group of twenty-five cases were treated with HLF regimen, and the other group of 23 cases were treated with ELF regimen. RESULTS: Of the 25 cases treated with HLF regimen, there was no complete remission (CR), but there were 12 partial response (PR), 11 no response (NC), and 2 had progressive disease (PD). The response rate (RR) was 48.0%. Of the 23 patients treated with ELF regimen, there was no CR, there were 9 PR, 11 NC, and 3 PD. The RR was 39.1% (P > 0.05). The main toxicity was myelosuppression and stomatocace. Grade III-IV stomatocace in HLF regimen group (68.0%) was more commonly seen than that in ELF regimen group (39.1%, P < 0.05). There was no cardiac or renal toxicity observed. CONCLUSION: HLF regimen is promising for treatment of advanced gastric carcinoma in middle-aged and elderly patients with the merits of low toxicity affecting heart, kidney and bladder except stomatocace, which is worthy of further clinical trial. PMID- 11778281 TI - [The digestive functions of the stomach after esophagectomy with vagus nerve preserved or severed in esophageal cancer patients: a comparative study]. AB - OBJECTIVE: To study the feasibility, indication, and clinical significance of preserving the vagus nerve during esophagectomy for patients with cancer of the esophagus. METHODS: The digestive functions of the stomach were studied and compared before and after esophagectomy in patients with vagus nerve intact (n = 11) or severed (n = 12). RESULTS: According to Angorn's grading system, patients with vagus nerve preserved (VNP) had less symptoms after operation than those with vagus nerve severed (VNS). The gastric emptying time of the intrathoracic stomach in patients with VNS was much prolonged compared with that in patients with VNP. There was no significant difference in the preoperative and postoperative mean basal gastric acid output and the 24-hour pH monitoring in patients with VNP, while in VNS patients they were significantly decreased after operation. Fasting serum gastrin level in VNS patients was significantly elevated but this was not observed in VNP patients. Fibroptic endoscopic examination revealed higher incidence of postoperative atrophic gastritis in VNS than in VNP patients. CONCLUSION: Preservation of the vagal trunks during surgical resection for cancer of the esophagus is beneficial to keep the postoperative digestive functions of the stomach in a better condition. PMID- 11778282 TI - [Diagnosis and treatment of bile duct tumor thrombus in patients with hepatocellular carcinoma]. AB - OBJECTIVE: Tumor thrombus in the bile duct (BDT) is very rare in patients with hepatocellular carcinoma (HCC). The prognosis of the patients with BDT is very poor. To improve the prognosis, HCC patients with BDT were retrospectively reviewed. METHODS: Retrospective study was performed in 16 cases of HCC with BDT found in authors' institute from July 1987 to Oct. 1998. Factors affecting prognosis were analyzed. RESULTS: The occurrence rate of BDT as 0.76% (16/2100). Removal of BDT and HCC was performed in all but one patients. Fourteen patients were followed-up for over 1 year after operation. The 1-year survival and recurrence rate was 71.4% (10/14) and 57.1% (8/14), respectively. Three female patients survived over 4, 6, and 12 years, respectively. CONCLUSIONS: Early detection and diagnosis, surgical removal of primary tumors and BDT are the key points to prolong the survival time of patients. PMID- 11778283 TI - [Infusion chemotherapy and chemoembolization of liver metastases from cancer of the alimentary tract]. AB - OBJECTIVE: To evaluate the efficacy of hepatic artery infusion chemotherapy and chemoembolization in the treatment of liver metastases from alimentary tract cancer. METHODS: A total of 92 patients with unresectable liver metastases from alimentary tract cancer was treated 316 times by hepatic artery infusion chemotherapy and chemoembolization. Of the 92 patients, only infusion chemotherapy was performed in 29 patients, and infusion chemotherapy and chemoembolization in 63 patients. Chemotherapy was carried out with a combination of epirubicin and/or cisplatin, mitomycin-C, calcium folinate and 5-fluorouracil. Embolization was accomplished with lipiodol ultra-fluid or lipiodol ultra-fluid and gelatin sponge. Response rates were assessed by CT scanning. RESULTS: An overall response rate (CR + PR) of the cases was 45.7%. The mean survival period of 92 patients was 19.6 months. The 0.5-, 1-, 2-, 3- and 5-year survival rate was 95.7%, 73.8%, 30.9%, 17.6% and 9.9%, respectively. Best therapeutic results were obtained in 9 cases with single metastatic focus in the liver, with a mean survival period of 31.2 months. There was no severe side effect or complication. CONCLUSION: Treatment by transcatheter hepatic artery infusion chemotherapy and chemoembolization is beneficial to patients with metastatic cancer of the liver. PMID- 11778284 TI - [Long-term results of total versus partial laryngectomy for the treatment of squamous-cell carcinoma of the larynx]. AB - OBJECTIVE: To analyze the long-term effects of total versus partial laryngectomy for the treatment of squamous-cell carcinoma of the larynx. METHOD: Of 423 patients with laryngeal carcinoma surgically treated, 327 had supraglottic cancer and 96 had glottic cancer. Total laryngectomy was performed in 243 patients (210 supraglottic and 33 glottic cancers) and partial laryngectomy in 180 patients (117 supraglottic and 63 glottic cancers). RESULTS: The overall 5-year survival rate of patients with supraglottic carcinoma was 72.9%. That of patients treated by total and partial laryngectomy was 70.1% and 77.4%, respectively (P > 0.05). The overall 5-year survival rate of patients with glottic carcinoma was 86.0%. That of patients treated with total and partial laryngectomy was 72.2% and 92.3%, respectively (P < 0.05). CONCLUSION: The long-term result of partial laryngectomy for glottic carcinoma is as good as total laryngectomy, and for supraglottic carcinoma, partial laryngectomy is superior to total laryngectomy. Partial laryngectomy is recommended to treat patients with squamous-cell carcinoma of the larynx. Patients so treated have a better quality of life. PMID- 11778285 TI - [Biotherapy and biochemotherapy of patients with malignant melanoma]. AB - OBJECTIVE: To evaluate the efficacy of postoperative biochemotherapy on survival of patients with malignant melanoma. METHODS: One hundred and five patients with malignant melanoma received postoperative biotherapy/biochemotherapy or radiotherapy/chemotherapy. The median time of follow-up was 3 years (from 1 to 5 years). RESULTS: The median survival time (MST) in the whole series of patients was 27 months (range: 2-72 months). The MST in patients received postoperative biotherapy/biochemotherapy (57 cases) was 32 months with a 3-year survival rate of 36.8%. That in patients received postoperative radiotherapy/chemotherapy (54 cases) was 20 months. CONCLUSION: Biotherapy/biochemotherapy following surgery may significantly improve survival in patients with malignant melanoma. PMID- 11778286 TI - [Cancer pain and its influence on cancer patients' quality of life]. AB - OBJECTIVE: To study cancer pain and its effect on cancer patients' quality of life. METHODS: Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and Brief Pain Inventory (BPI) methods were used to investigate cancer pain, its effect on patients' quality of life and management in 200 cancer inpatients. RESULTS: The incidence of cancer pain was 69%, including 21.5% with mild pain, 19% with moderate pain and 28.5% with severe pain. Moderate and severe pain occurred more frequently in patients with cancer of the digestive tract. No correlation was found between pain and stage of the disease, but was closely associated with bone metastasis. Regardless of its severity, cancer pain seriously affected patients general activity, mood, walking ability, normal work and sleep. With the seriousness of pain, the patients were more affected. However, there was no obvious difference between moderate and severe pain in terms of their effect on the patients' joy of life and relations with people. The effect of moderate pain on patients' mentality appeared earlier than did severe pain. Among patients with cancer pain, 41.3% of them did not receive proper treatment. Only 52.1% of patients with severe pain were given strong opioids, which is far from the anti-pain standard set forth by the WHO. CONCLUSION: Cancer pain is one of the most important factors which affect cancer patients' quality of life. For adequate control of cancer pain, there is still a long way to go to achieve WHO's goal. PMID- 11778287 TI - The electronic health record. Files 2 computers. Healthcare--the pivotal application for smart cards? PMID- 11778288 TI - From blunderbuss to specifics. PMID- 11778290 TI - Results of evaluation of the vascular surgery awareness day. PMID- 11778289 TI - Oman towards electronic medical records. PMID- 11778291 TI - Top 10 trends in health care for 2002. The challenges of capacity, capital, and consumerism. PMID- 11778292 TI - Looking "backward". Top 10 predictions were 110% accurate in 2001, including "wild card" call on terrorism. PMID- 11778293 TI - Person of the year 2001. Interview by Patricia A. Costante, Leah Z. Ziskin and Paul J. Hirsch. PMID- 11778294 TI - Turning your practice around. AB - The techniques of managing a medical practice are no different from those required to manage any other business. Planning is the first step, and establishing a realistic budget is essential to creating a successful plan. Knowing your patients and the sources of your revenue are next. Understanding the weaknesses within your practice and developing courses of action to correct them is essential. This includes developing ways to increase revenue as well as control expenses. Once a plan has been developed a basis for monitoring that plan is required. We suggest tracking financial performance monthly. If these basic management techniques are put into place, the actions discussed above will become both easier and more effective. PMID- 11778295 TI - The whole truth. The risk of going from bad to worse in malpractice litigation. PMID- 11778296 TI - The UMDNJ-School of Public Health. PMID- 11778297 TI - Opinion: the pharmaceutical industry welcomes governor-elect Jim McGreevey. PMID- 11778298 TI - Cotton-top. PMID- 11778299 TI - Handheld healing. PMID- 11778300 TI - Influenza and pneumococcal vaccination. PMID- 11778301 TI - Case of the month. Osteoporosis in a postmenopausal woman. PMID- 11778302 TI - What makes a general surgeon. PMID- 11778303 TI - Err or error. PMID- 11778304 TI - AMA restores Hippocratic Oath to medical ethics. PMID- 11778305 TI - Advise and consent. PMID- 11778306 TI - Disclosing "unanticipated outcomes" to patients. PMID- 11778307 TI - Gearing up for HIPAA business associate contracts. PMID- 11778308 TI - Anthrax: U.S. bioterrorism affecting Missourians. PMID- 11778309 TI - Anthrax prophylaxis, treatment, and reporting guidelines. PMID- 11778310 TI - What you need to know about anthrax today. PMID- 11778311 TI - Diabetes and heart disease. PMID- 11778312 TI - [Initial studies of the application of the linear signal transfer theory in evaluating diaphanoscopic examinations exemplified by rheumatism diagnosis]. AB - Rheumatoid arthritis affecting the small joints--in particular the fingers--has advantageous geometry for the transmission of near-infrared (NIR) light. Examination of the optical properties of tissues has revealed that as a result of changes to the capsule and synovial fluid there is a considerable increase in photon scattering already in the early stages of the disease--in particular around 685 nm. This suggests the appropriateness of analysing the photon density profile resulting from punctiform irradiation of the joint. In a first approximation, the point spread function of transmitted photon density is confirmed to be proportional to a Gauss distribution, as suggested by Arridge. In accordance with the linear signal transfer theory, therefore, it is possible to establish a virtual transfer system described by a first-order differential equation. (The tissue optical conditions mu a << mu's and mu a = constant (mu a = absorption coefficient) were assumed). The parameter mu's (= reduced scattering coefficient) was determined by linear approximation of the Gauss distribution to the calculated or measured point spread function. For selected patient data, the mu's was determined in healthy and diseased finger joints (e.g. 10.1 cm-1 and 26.8 cm-1, respectively), and the results were in good agreement with those obtained experimentally. PMID- 11778314 TI - [Risk from electric current greater than assumed]. AB - Despite its importance for the assessment of the effects of electric current and for technical safety considerations, not only does the electric perception threshold remain uncertain, but essential questions are still unanswered and contradictions unresolved. Via measurements at 908 persons randomly selected from the general population, including 708 adults (349 men, 359 women aged between 16 and 60 years), the problems of extrapolation to the general population and adequate statistical representation have now been overcome for the first time. The results show that existing assumptions about electric current perception need to be drastically corrected. It has been shown that the assumed electric perception threshold has been too high by a factor of 10, and that women are substantially more sensitive than men. This means that present gender-specific differences in electrosensitivity need revising. On the basis of the evidence of significant underestimation of the reaction variability in the general population, present assumptions on safety limits and safety factors urgently need to be reviewed. By no means can a relaxation of safety regulations be justified. PMID- 11778313 TI - [Microdialysis for metabolic monitoring during septicemia]. AB - Currently, metabolic changes in ICU patients in critical states are determined mainly by indirect laboratory parameters (e.g. blood lactate). Microdialysis is a new means of performing metabolic monitoring that permits organ-specific objectification on the basis of interstitial fluid samples. Continuous endotoxin infusion was administered to 10 female pigs and, in addition to hemodynamic monitoring, lactate and glycerol in the subcutaneous, intramuscular and hepatic tissue were measured by microdialysis. The interstitial concentrations of lactate and glycerol rose significantly under endotoxaemia and showed an earlier increase than blood lactate levels. Microdialysis is simple to apply, appears to be a suitable means of obtaining important information about cellular metabolic changes in different tissues of the critically ill patient, and can detect subtle changes that laboratory parameters can identify only later and incompletely. PMID- 11778315 TI - [Movement behavior of teeth and dental implants in periotest measurement in occlusion--an in vitro study]. AB - Early diagnosis of periodontal disease is essential for the planning of restorative, prosthetic and surgical treatment. The usual clinical methods are mostly subjective. Although the Periotest device has been specially developed for the diagnosis of periodontal disease, it can also be used to aid occlusal adjustment after insertion of inlays or artificial crowns. To investigate this application of the Periotest, a jaw model with idealized dental crowns incorporating motion and force sensors has been constructed. Motion and force are recorded during measurements with the Periotest. The maximum amplitudes in the apical (vertical) direction obtained with unpolished occlusal points increased with increasing occlusal load. With polished contact points, the maximum values in the apical direction revealed no dependence on occlusal load. The maximum amplitudes of movement and force in the oral (horizontal) direction decrease with increasing occlusal load both with polished and unpolished contact points. With the first, the teeth appear to slide one upon the other such that the overall distance between them remains unchanged, and no additional apical forces develop. In the case of rough contact points, additional forces develop, and falsify Periotest measurements. PMID- 11778316 TI - [Preventing fat embolism syndrome (FES) in implantation of cemented hip endoprosthesis shafts with a trans-prosthetic drainage system (TDS)]. AB - In vitro studies with the transprosthetic drainage system (TDS) have revealed a reduction in intrafemoral pressure in cemented total hip prosthesis. The aim of the present study was to establish whether the incidence of fat embolic syndrome (FES) is also reduced. Ten patients underwent standardized cemented total hip replacement using TDS under standardized general anaesthesia. The usual peri operative monitoring measures were extended to include cardiopulmonary monitoring (pulmonary artery catheter, intra-arterial blood pressure) and two-dimensional transoesophageal echocardiography. Previous studies had reported an increased risk for fat embolic syndrome with conventional, and even with vacuum cementing techniques. Our recorded cardiopulmonary data and the data provided by two dimensional transoesophageal echocardiography show a significant reduction in pulmonary embolism with TDS. This technique can be recommended in particular for high-risk patients (osteoporosis, elderly patients) and the implantation of long femoral stems. On the basis of the clinical data, a new femoral stem allowing the use of the TDS technique is being developed. PMID- 11778317 TI - [Mechanical study of spinal interbody implants--characteristics and limits of standardized testing]. AB - Spinal interbody fusion has proved to be a useful procedure for the surgical stabilization of spinal segments, for which fusion cases made of metal or reinforced polymers are increasingly being used. For the mechanical testing of spinal interbody implants, a test setup has been developed on the basis of an ASTM proposal. Initially, testing of lumbar fusion cages made of CFRP (carbon fibre reinforced polymer) was carried out. The implants (UNION Cages, Medtronic Sofamor Danek), which are characterised by their radiolucency on radiography, NMR and CT scans, have a cube-shaped body with three table-tracks on the under and upper surfaces. The cages were tested at different loads. Modifications of the proposed standardized method were carried out to enable implementation of implant oriented testing. The tested cages were shown to have adequate axial compression, shear and torsional strengths with regard to the implant body. The maximum axial compression force tolerated by the table-tracks was less than the maximal potential loading of the lumbar spine, and, with account being taken of implant design, consequences with regard to surgical technique were drawn. As dictated by the geometry of the table-tracks, parallel grooves have to be made intra operatively in the vertebral end plates. Axial compressive loads then act on the implant body, and the table-tracks are protected from damage. To avoid in vivo failure, the tested cages should be implanted only when this specific surgical technique is employed. Using supplementary anterior or posterior instrumentation, in vivo failure of the table-tracks under physiological spinal loading is not to be expected. PMID- 11778318 TI - ["No time to recover one's breath"--bronchial asthma between treatment possibilities and sobering reality]. PMID- 11778319 TI - [Asthmatic airway inflammation]. AB - Asthma is an inflammatory disease of the airways even in its clinically mildest manifestation. The pathogenesis is based on complex interactions between inflammatory cells, soluble signal molecules (mediators) and structural cells as well as extracellular components of the airways. Bronchial inflammation is closely associated with bronchial hyperreactivity, airways obstruction and asthmatic symptoms. Airways inflammation causes airflow limitation via (1) acute muscular bronchoconstriction, (2) formation of mucous plugs, (3) thickening of the airway wall, and (4) fibrotic remodelling of the airways ("Remodelling"). The insights into bronchial inflammation as the basis of asthma is of principle significance for the diagnosis, prevention, and treatment of the condition. PMID- 11778320 TI - [Diagnosis and differential diagnosis of bronchial asthma]. AB - Asthma and COPD (chronic obstructive pulmonary disease) are the most important obstructive pulmonary diseases. Patient's history and physical evaluation give major hints of the underlying disease. Further diagnostic measures comprise lung function analysis including spirometry, plethysmography and--in severe cases- blood gas analysis. Bronchial hyperreactivity may be quantified with an unspecific inhalative provocation test. In many cases allergic diseases are accompanied by asthma. Thus, allergy tests--particularly skin prick tests--have to be carried out. To further define an underlying allergy, in some cases even specific inhalative provocation tests have to be performed. X-ray of the thorax and other imaging techniques, detailed blood analysis, further diagnosis of the upper respiratory tract and the cardiac system may have to be carried out a) to quantify the effects of a severe form of asthma or COPD on other organs, and b) for differential diagnostic examinations. PMID- 11778321 TI - [Biophysical basics of aerosol therapy in bronchial asthma]. AB - For an effective inhalation therapy with aerosols the drug itself but also the inhalation device have to be considered. Several biophysical parameters influence the deposition in different regions of the respiratory tract. Particle size and the breathing pattern of the patient are the most important factors and have to be considered. PMID- 11778323 TI - [Asthma in children]. AB - Asthma is a disease of chronic airway inflammation characterized by reversible airway obstruction often beginning in early childhood. Antiinflammatory drugs such as nedocromil, DNCG, cysteinyl leukotrienes or inhaled corticosteroids are efficient and widely recommended. Yet there is a lack between therapeutic possibilities and outcome: too many patients are treated too late, with the wrong drugs in a wrong way, and their compliance is poor. In children less than two or three years of age the diagnosis of asthma is difficult. But it is highly important to start therapy early to avoid irreversible damage of the lung. Therefore a long-term antiinflammatory treatment with the least side effects should be administered as soon as the diagnosis of asthma is confirmed or even presumed. PMID- 11778322 TI - [Asthma therapy for adults]. AB - The goal of asthma management is to achieve control of the condition. This essentially requires environmental control measures (allergen avoidance) and patient training and education. Drug treatment comprises anti-inflammatory (corticosteroids), and bronchodilatory controller therapy (long-acting beta 2 sympathomimetics, leukotriene receptor antagonists, retarded theophylline) as well as bronchodilatory medication as required (short-acting beta 2 sympathomimetics). The number and frequency of pharmacologic therapy relates to the severity of the clinical presentation. The combination of certain controller drugs (corticosteroids with long-acting beta 2-agonists, corticosteroids with leukotriene receptor antagonists, and beta 2-agonists with leukotriene receptor antagonists) yields a synergistic therapeutic effect as well as a compliance advantage. PMID- 11778324 TI - [Reimbursement and importance of hyperbaric oxygenation for diabetic foot ulcers in German publically funded ambulatory health care]. AB - The Standing Committee of Statutory Health Insurance Physicians and Sickness Funds is the legal body that makes decisions on reimbursement for health care services in the German ambulatory health care sector. In 1994, the Committee declined the reimbursement of hyperbaric oxygen therapy (HBO). In 1999, a new deliberation of the efficacy, appropriateness and cost-effectiveness of HBO was initiated as the proponents of this technology claimed that the efficacy of HBO had since been proven in clinical trials. The deliberation was announced and published in the journal of the German Medical Association (Deutsches Arzteblatt) and the federal register (Bundesanzeiger). All institutions, groups, and interested individuals were given the opportunity to provide a written statement. The statements and, in particular, the scientific literature cited in those statements, were critically appraised by the Committee. In addition, the Committee conducted a thorough review of the literature, guidelines and status of the therapy in other health care systems. More than 40 potential indications for the use of HBO were reviewed by the committee. One indication was for diabetic foot ulcers. Most clinical trials related to this field represented only retrospective case series, which, in view of the established therapies, cannot be used as a sound basis for the acceptance of HBO as a new technology for the therapy of diabetic foot ulcers. Some studies were planned as randomized controlled trials but had serious methodological flaws in conduct and analysis. The main problems were the low numbers of patients included and serious inbalances of important and well known prognostic factors between the treatment groups. Systematic reviews that were published in the international literature after the decision of the Committee drew similar conclusions in view of the methodological flaws in the clinical trial data. In summary, the Committee decided once again to decline coverage of HBO in German ambulatory health care. PMID- 11778325 TI - The implementation of guidelines in The Netherlands. AB - A comprehensive system for quality improvement in General Practice has been developed in the Netherlands during the last decade. The basic principles of the quality system are discussed. Practice Guidelines are developed by GP's for GP's in a four step procedure. A range of methods and products based on the guidelines is produced to enhance the implementation of practice guidelines. PMID- 11778326 TI - [The importance of neuronavigation in endoscopic operations in neurosurgery]. AB - Intracranial endoscopy as minimal invasive surgery for the treatment of hydrocephalus and intracranial cysts cannot be disregarded after 10 years of clinical practicing. The advantages are low traumatization of brain tissue and good visual control of the operation field. Neuronavigation qualifies as a method of increased operation safety for lesions which are deep seated or difficult to access. A combination of both systems partially neutralizes the respective disadvantages. On the one hand, the neuronavigation ensures the endoscopic approach up to the intracranial caverns and especially supports the endoscopy in cases of bad vision or pathologic anatomy. Endoscopy, on the other hand, enables the surgeon to recognize discrepancies and mistakes of the neuronavigation due to optical control. Increased expenses and time and staff requirements are counterbalanced by the increased cumulated operation safety. An advantageous side effect of the combination of neuronavigation and intracranial endoscopy is the high learning potential for assistants. For all these reasons the application of neuronavigation in intracranial endoscopy is considered very important and strongly recommended. PMID- 11778327 TI - [On the stressful state of affairs between and social and confinement rights. Do confinement rights belong to medicine more than to social laws?]. PMID- 11778328 TI - Distal radius fracture: the rationale of a classification. AB - A thorough review of both historical and contemporary classifications of distal radial fractures is presented. Critical analysis of older and newer classifications clearly shows the difficulty of including all the necessary parameters associated to a distal radius fracture in order to comprehensively assess the complexity of the lesion. The author has attempted to simplify the classification of distal radial fractures into five main groups according to the mechanism of injury. It includes the children fracture equivalent, the associated distal radioulnar joint lesions, and provides management recommendations. An alpha-numerical code is also provided for computer documentation. PMID- 11778329 TI - [Is there still a place for conservative treatment of distal radius fractures in the adult?]. AB - Contrary to Colles'opinion which pretended the fracture of the distal radius would heal without sequellae, many studies devoted to this problem showed that complications will affect one third of the cases (malunion, nerve compression, dystrophy, tendon rupture). It is important for the surgeon to know well the different fracture types, the general condition of his patient as well as his osteoarticular state to make the good choice of treatment. Our study shows that the nonoperative treatment will be chosen for any fracture type as far as it concerns an old or crippled patient, especially if there is an osteoporosis. On the contrary, for a young and active patient with a good bone quality, non operative treatment will be chosen as far as the fracture will be reducible and stable. If it is not, an osteosynthesis has to be done. Many studies already published tend to demonstrate that there is a correlation between anatomical and functional results. However, concerning elderly, this correlation tend to disappear with time. PMID- 11778330 TI - [Osteosynthesis of distal radius fractures by doral plate: advantages and disadvantages]. AB - Distal radius fractures remain a challenge. No one osteosynthesis procedure can solve all the problems. A method of analysis is necessary in order to choose the best tools. Open treatment of the fracture is logical but rarely performed. A review of the literature and the experience of the authors are reported in order to analyse the correct place of dorsal plating in distal radius fracture with dorsal displacement. The learning curve of the operative procedure and the design of the implants can explain the occurrence of several complications. The dorsal plate is effective against secondary dorsal displacement. This demanding procedure must be compared with other reported procedures (pining and external fixator) to define the advantages and disadvantages. PMID- 11778331 TI - ["Sandwich" osteosynthesis of the distal radius]. AB - In certain intra-articular fractures or post traumatic sequelae of distal radial fractures, it may be difficult to restore the normal anatomy and support the articular surface using a single surgical approach. A combined palmar and dorsal approach with double plating can be helpful in such cases. The author presents a series of six cases treated with two plates to support the palmar as well as the dorsal cortex. Results were favourable in five cases but one secondary displacement occurred because the metaphyseal defect was not bone grafted. PMID- 11778332 TI - [Utility of bone substitutes: study of 101 distal radius fractures]. AB - The aim of the present retrospective study was to evaluate the performance of bone graft substitutes currently in use. After exclusion of those with inadequate data for comparison, 70 out of the 101 operated fractures remained available for statistical analysis. Grafts were used in 38 cases: 23 were bone substitutes and 15 autogenous grafts. Distal radial inclination and lateral angles showed no significant difference. Analysis of ulnar variance showed the relative inability of intramedullary pinning to maintain radial length in the absence of graft. In contrast external fixators preserved radial length both with and without bone grafts, and with all types of graft material. TCH (hydroxyapatite and calcium phosphate) or autogenous bone grafts allowed intramedullary pinning to maintain radial length; whereas collagen matrix material was ineffective. We conclude that TCH and autogenous bone grafts have equivalent effectiveness despite potential bias in this study. PMID- 11778333 TI - [Interest in early active controlled mobilization and flexion following flexor tendon repair in zone 2]. AB - INTRODUCTION: Primary repair of flexor tendons in zone II of the hand and early post-operative rehabilitation is no longer challenged. However, early rehabilitation methods vary from one unit to another. Although currents techniques such as of Kleinert's and Duran's have brought considerable improvements in functional outcomes, they do not allow early active motion of repaired flexor tendons. METHODS: A promising method of active controlled mobilization has been proposed by the Bordeaux Hand Unit and adopted by our rehabilitation unity since 1995. The aims of this method are: to avoid of proprioceptive inhibition linked to passive methods and prevention of adhesions. This method has been assessed by a prospective study of 22 consecutive patients with average follow-up of 11.8 months. RESULTS: Our rating was based on the Strickland scoring technique. 81% of good and excellent results were observed. Our score rates confirm the results published by others authors who have applied the same active protocols. The results observed in our series tend to confirm the advantages of early controlled active mobilization techniques and lead us to pursue their application in the future. PMID- 11778334 TI - [Unilateral congenital aplasia of the scaphoid and dysplasia of the trapezium (a case report)]. AB - Aplasia of the carpal scaphoid bone in association with dysplasia of the trapezium is a rare disorder. A right-handed, 66 years old male, suffering from a trapeziometacarpal arthritis on the right side is reported. X rays, MRI and CT scan reveal an absence of scaphoid and a dysplasia of the trapezium. The lunate remains in place on the radius but is oriented in dorsi flexion. The capitate is dorsally and radially subluxated. Trapezium inclination of the joint at the base of the first metacarpal (trapezial tilt) is 32 degrees greater than on the opposite side which is normal (48 degrees). Radial styloid is hypoplasic. The scaphoid fossa is not covered with cartilage and subchondral sclerotic bone. The intercarpal joints show no trace of arthritis. There are no other deformation on the radial segment of the hand and the forearm. This congenital absence of scaphoid remains asymptomatic and well tolerated excepting the dysplasic trapeziometacarpal joint. PMID- 11778335 TI - The meaning of research utilization. A preliminary typology. AB - The preliminary findings of the meaning of research utilization as perceived by the bedside nurse provide some clues for promoting research utilization. Nurses must believe in the importance of nursing research to the profession, the individual clinician, and the patient. Nurse researchers should present their findings to the bedside nurse in a way that can be easily applied to the practice setting. Shaping a positive research mindset is important to the goal of a research-based practice. Infusing research findings throughout nursing courses, in addition to having a research course to learn basic critiquing skills, emphasizes the importance of nursing research to the individual student and encourages a seamless transition to clinical practice. The institutional setting wields a great deal of power when it comes to mandating practice changes. The institution must value research and embrace a continuing state of change by empowering the nursing staff to question the status quo. Research-focused university settings provide excellent opportunities to learn about the research process and share research findings. Policies and procedures should be updated regularly to reflect changes in the scientific base of nursing practice. Institutional support of research utilization fosters an environment that expects excellence in practice. Encouraging nurses to be more involved in nursing research activities and to value their role as data collectors has been shown to increase research awareness and utilization of findings. Nurses must believe they have the personal and professional power to change practice according to the evidence. This preliminary report has presented data that begin to describe what research utilization means to the bedside RN. The typology presented is grounded in the reality of the practicing nurse and provides important insights for those who wish to foster a research and evidence base for professional nursing practice. As further qualitative and quantitative information about the phenomenon of research utilization is collected, an integrated approach to concept clarification can occur. PMID- 11778336 TI - Using nurse-sensitive outcomes to improve clinical practice. AB - With the many uncertainties in the current health care milieu and continuing movement from general guidelines to ensure an optimal practice approach, it is especially vital that critical care nurses facilitate a research culture in their workplace and strive to improve clinical practice through understanding and evaluating research. Outcomes research helps to identify discipline-specific accountability in patient care. Through understanding the basic aspects of outcomes research and the issues that influence nurse-sensitive outcomes, the critical care nurse is informed and can make clearer and appropriate choices in patient care. Outcomes research continues to be instrumental in defining a base for nursing practice. Although it is not necessary or even desirable that all nurses conduct research, nurses are accountable for providing scientific and appropriate care to ensure the optimal outcome for the patient. PMID- 11778337 TI - The Iowa Model of Evidence-Based Practice to Promote Quality Care. AB - The UIHC Department of Nursing is nationally known for its work on use of research to improve patient care. This reputation is attributable to staff members who continue to question "how can we improve practice?" or "what does the latest evidence tell us about this patient problem?" and to administrators who support, value, and reward EBP. The revisions made in the original Iowa Model are based on suggestions from staff at UIHC and other practitioners across the country who have implemented the model. We value their feedback and have set forth this revised model for evaluation and adoption by others. PMID- 11778338 TI - Using evidence-based approaches to strategically respond to the nursing shortage. AB - The purpose of this article is to describe how evidence-based methods were used to create a strategic plan for recruitment and retention of nursing staff. Collecting data on the nursing workforce, thorough review and critique of the literature, and linking the literature to strategic goals and imperatives were accomplished. The success of the strategic plan requires much more than an evidence-based approach, however. Indeed, success is largely dependent on a radical change in culture. The long view is to create a patient-centered culture where spiritual values are integrated with knowledge and skill, resulting in competent caring for patients and families. That vision requires the recruiting and retention of competent and caring nurses. To retain rather than recruit nurses, the organizational culture must become a good place within which to work. Espousing spiritual values is not enough. Current employees and newcomers must recognize these values in the behaviors of staff, managers, and leaders. Beyond evidence-based methods, values integration is critical. In the end, it is the values-based behaviors of people rather than the evidence or the strategic plan that should allow this system to effectively confront and manage the continuing nursing shortage. PMID- 11778339 TI - Cultural competence for critical care nursing practice. AB - Cultural information should be critically examined and appropriately used in the context of individual relationships. The increased ethnic minority population in the health care system mandates that differences be recognized and responded to. Furthermore, the linear and technologic environment of the critical care unit intensifies the potential for cultural dissonance and disempowerment of ethnic minorities. CCNs must be creative and willing to transform nursing care to meet the needs of all. Knowing one's self, being aware of limitations, and understanding the influence of culture on others are essential to being culturally competent and an effective CCN. Because nursing remains dominated by individuals from the majority culture, many have little experience with persons of diverse ethnicity. Increasing cultural knowledge and the numbers of minority nurses and translators in the ICU are only the start to providing holistic care to this country's diverse population. Patient outcomes should improve and nurses are greatly enriched from an understanding and achievement of cultural competency. PMID- 11778340 TI - Typical and atypical symptoms of myocardial infarction among African-Americans, whites, and Koreans. AB - Most public education about the clinical symptoms of MI and the appropriate response to those symptoms has been designed to reach educated segments of the white population based on data gathered from white men. As a result, AAs and Korean-Americans may be less alert to chest pain, less likely to relate this symptom to heart attack, and less likely to seek treatment promptly. Our findings provide a race-specific database on CHD risk factors and types of MI symptoms, which should be of particular interest to the trauma and emergency care nurse as well as to the coronary care nurse. AAs and Koreans experienced chest pain as frequently as whites, but AAs experienced the atypical symptoms of dyspnea and fatigue more often, and Koreans experienced dyspnea, perspiration, and fatigue more often than whites. This information can be helpful in developing public education programs on MI that are sensitive to our increasingly diverse population. In the acute and critical care setting, these data assist the nurse to recognize that "classic" signs and symptoms of acute MI may not be classic for all racial and ethnic groups. This awareness can lead to more culturally sensitive assessment tools and educational interventions, earlier recognition of acute MI with more appropriate triage decisions, more aggressive treatment, and a reduction in morbidity and mortality of these high-risk groups. PMID- 11778341 TI - Translating research into practice. Implications of the Thunder Project II. AB - The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress. PMID- 11778342 TI - Pressure ulcer prevention and treatment. A synopsis of the current evidence from research. AB - Foam alternatives to the standard hospital foam mattress can reduce the incidence of pressure ulcers in people at risk. The relative merits of AP and CLP devices and of the different AP devices for pressure ulcer prevention are unclear. There is some evidence from one study to suggest that LAL beds may reduce the incidence of pressure ulcers compared with standard intensive care beds. There is insufficient evidence to make conclusions on the value of various CLP devices and sheepskins as pressure ulcer prevention strategies, although Australian Medical Sheepskin was an effective preventive strategy in a recent study. There is evidence from two trials that air-fluidized therapy may improve pressure ulcer healing rates. There is insufficient evidence to make conclusions on the value of other beds and mattresses as pressure ulcer treatments. There is insufficient evidence to recommend any particular wound dressing or debridement technique. Research about pressure ulcer prevention and treatment is generally conducted on a small scale and is of poor quality; few economic evaluations have been undertaken of pressure area care strategies. Only when a clinically relevant research agenda has been developed and appropriate research methods have been used in sufficiently large studies can evidence-based pressure ulcer prevention and treatment be a possibility. Until then, nurses and other health care professionals can only rely on what little research evidence exists together with their professional judgment to make decisions in this field. PMID- 11778343 TI - Committing to evidence-based skin care practice. PMID- 11778344 TI - Family presence during cardiopulmonary resuscitation and invasive procedures. A research-based intervention. PMID- 11778345 TI - Critical caring. Promoting good end-of-life care in the intensive care unit. AB - Changing the culture in the ICU to include palliative care interventions along with curative interventions is already underway. Further work is needed, however. This is a role for the critical care nurse. Critical care nurses can be involved in research and education to enhance their future practice in end-of-life care. Research to establish evidence-based protocols for use in patients who require palliative care in the ICU needs to be done. Critical care nurses can prepare themselves for carrying or dying patients by attending palliative care seminars and continuing education courses or by taking a short clinical sabbatical or internship in a local hospice to observe and help give end-of-life care. Hospice nurses can be invited to the ICU to give inservice sessions and to help nurses and other staff understand the transition to dying, including the services that need to be offered to the patient and the family. Nurses from the hospital palliative care team can consult and be available for follow-up. Promoting good end-of-life care should be a goal for all intensive care nurses and critical care units. This goal is reached one patient at a time. PMID- 11778346 TI - Translating research into practice. Considerations for critical care investigators. AB - Experimental multisite studies are needed to test adoption interventions that promote use of evidence-based guidelines in critical care practice. A research model (see Fig. 2) based on Rogers' diffusion of innovation model provides a conceptual guide for selecting interventions to test in translational research studies. Studies should address the four major areas of innovation adoption: (1) characteristics of the guideline, (2) users of the guideline, (3) methods of communicating the guideline, and (4) the social system in which it is being adopted. It is imperative that researchers study which interventions are most effective in promoting use of critical care evidence-based practices by nurses and physicians and how the social system of critical care environments affects adoption of such practices. Without this empiric knowledge, health care systems have little guidance in how to most effectively promote adoption of scientific evidence to improve care of critically ill patients. PMID- 11778347 TI - Research strategies for clinicians. AB - If there is a story waiting to be told about nurses and research, it is this: research is part of our past, our present, and our future. Research gives "caring" a mental muscle that makes it stronger than caring would be without it. Since the Crimean War, research has been a foundational cornerstone of the profession. Florence Nightingale espoused caring and human touch but not without also observing and measuring important patient outcomes that identified the spread of infection via human contact. As a new generation of nurses emerges, we who have come before might serve them well to role model what we know: that strong research is strong nursing and that obtaining and using evidence in nursing practice results in better outcomes for those patients and families we serve. Is the story waiting to be told your story? Part of the story of nursing waiting to be told is your story. Regardless of why you embarked on your career in nursing and regardless of where your journey has taken you to this point, you are a part of the twenty-first century body of nursing, and your individual contribution is an important one. Listen to your patients with an ear toward measuring and evaluating outcomes. Reflect on the care you provided, the interventions you had to offer, and why. Should something have been different? Could something have been better? Find out ... measure it. PMID- 11778348 TI - The impact of cholesterol lowering on patients' mood. AB - This study compared mood changes in 212 patients treated for hypercholesterolemia, as a function of their level of adherence to dietary recommendations. Assessments of mood (anxiety, depression, and hostility), measured by the Profile of Mood States, were obtained at baseline and 3-, 6-, and 12-month follow-up. Adherence to diet was categorized as low, medium, or high based on the Food Record Rating. Repeated-measures ANOVAs showed a significant decrease over time for anxiety, total cholesterol (TC), and low-density lipoproteins (LDL). A multiple regression was performed to determine if reductions in TC or LDL were associated with the anxiety decrease. The model for anxiety change was highly significant and included gender, baseline anxiety, number of stressful events, psychological stress, baseline level of adherence to diet, gender x adherence interaction, and change in TC x adherence interaction. In conclusion, cholesterol lowering did not negatively affect patients' moods. However, those who adhered poorly but nonetheless showed stable or reduced TC exhibited a greater decrease in anxiety. PMID- 11778350 TI - The psychosocial impact of cancer and lupus: a cross validation study that extends the generality of "benefit-finding" in patients with chronic disease. AB - Mohr et al. (1999) described the psychosocial effects of multiple sclerosis (MS) from the patient's perspective. Three factors emerged: demoralization, benefit finding, and deteriorated relationships. The benefit-finding factor suggested that some patients with MS benefited from their illness. We investigated the generalizability of these results by replicating the Mohr et al. study using patients with two diseases, cancer (N = 56) and lupus (N = 31). All participants completed the questionnaire developed by Mohr et al. along with the Profile of Mood States. When the data were analyzed, results showed a three-factor solution very similar to the one reported by Mohr et al. Scores on the demoralization factor were positively related to total mood disturbance and average pain ratings and inversely related to benefit-finding. Conversely, patients who perceived more benefits from their illness suffered less. We conclude that benefit-finding is not unique to patients with MS but occurs in patients with other chronic diseases. PMID- 11778351 TI - Relationship of stereotypic beliefs about physicians to health care-relevant behaviors and cognitions among African American women. AB - A great deal of basic social psychological research has demonstrated that stereotypes affect judgments, behaviors, and decisions with respect to individual group members. However, almost no research has applied social psychological theories of stereotypes to understanding health behavior. The purpose of the present study was to examine the relationship between stereotypic beliefs about physicians and health care-relevant behaviors and cognitions. Fifty-nine African American women were recruited from community venues to complete self-report, anonymous questionnaires measuring beliefs about physicians and health care utilization, satisfaction, and intentions. Participants who perceived physicians positively overall, and as competent and warm, reported greater health care utilization and higher satisfaction with their current health care, controlling for perceived general health status. These results suggest that interpersonal social cognitive expectancies play a role in health care-related behaviors and cognitions. PMID- 11778349 TI - Lymphocyte proliferation is associated with gender, caregiving, and psychosocial variables in older adults. AB - We examined lymphocyte responses to mitogens [phytohemagglutinin (PHA), concanavalin A, pokeweed] in spouse caregivers of persons with Alzheimer's disease (n = 82; mean age = 69.4) and noncaregiver spouses (n = 83) group matched on age and gender. Data were collected at study entry (T1) and 15-18 months later (T2). In men (n = 52), a depressed mood factor was negatively related to all mitogen responses at T1 and PHA at T2. Loneliness was the most important variable in the depressed mood factor. No relationships occurred in women (n = 113). At T2 an anger expression factor (anger-out--anger-control) was negatively related to all mitogen responses in caregivers. Anger-out was the most important variable for anger expression. Depressed mood at T1 predicted residualized changes in PHA at T2 in men. In conclusion, men with higher depressed mood and caregivers with higher anger expression may be at risk for lower proliferation responses. PMID- 11778354 TI - [Thromboembolism in travelers]. AB - The association between long haul travel and the risk of venous thromboembolism are suspected for long time. Mostly air travel related thrombosis series have been reported in the literature. Risk factors can be classified as: 1. travel related factors (coach position, immobilization, prolonged air travel, narrow seat and room, diuretic effect of alcohol, insufficient fluid intake, dehydration, direct pressure on leg veins, rare inspiration). 2. air plane related risk factors (low humidity, relative hypoxia, stress). 3. patient related factors (hereditary and acquired thrombophylia, previous deep venous thrombosis, age over 40, recent surgery or trauma, gravidity, puerperium, oestrogen containing pills, varicosity, chronic heart disease, obesity, fever, diarrhoea, vomiting, smoking). No patient related factors were found in some cases. To reduce the hazards air travellers are rightly concerned to know the level of the risk and the airlines should be responsible for this information. People should discuss with their physician what prophlylactic measures should be taken, such as compression stockings or low molecular weight heparin. Not only flight but car, bus and train travellers are also at risk of developing venous thromboembolism. Long haul travel alone is a separate risk factor for venous thromboembolism. PMID- 11778353 TI - [The pathogenesis of diabetic and hepatic neuropathies]. AB - The pathomechanism of neuropathies associated with diabetes and chronic liver diseases are poorly understood. Both metabolic and vascular factors are involved in the pathogenesis of diabetic neuropathy. It seems likely, that microangiopathy on the one hand and changes of various metabolic pathways due to hyperglycaemia on the other hand are much more related to each other than it was suggested previously. Nitric oxide may be the link between the metabolic and vascular hypotheses of diabetic neuropathy. Both reduced endoneurinal blood flow and increased oxidative stress leads to reduced nitric oxide synthetase activity. There are widespread inter-relationships between the most relevant metabolic changes included polyol pathway hyperactivity, reduced myoinosit concentration, advanced glycation end products formation, increased oxidative stress and lipid peroxidation. Changes of hemorheological conditions and primary hemostasis leeds to hyperviscosity just as to increased activity of the coagulation system. Among patients with chronic alcoholic liver diseases the direct toxic effect of alcohol is of particular relevance, however, malabsorption, impairment of axoplasmatic transport, changes of intermedier metabolism as well as thiamine and pyridoxine deficiency are of importance as well. The role of decreased insulin sensitivity and various degrees of glucose intolerance related to chronic liver diseases are still underestimated. Impairment of proteoglycan metabolism as well as increased oxydative stress are thought to be important factors in the pathogenesis of both diabetic and hepatic neuropathies. Glucose autooxidation and enhanced lipid peroxidation contribute to increased oxidative stress in patients with diabetes and chronic liver diseases as well. Vitamin E deficiency, autoimmun processes, circulating immune complexes, cryoglobulinemia, just as changes of vascular responsiveness associated with nitric oxide activity plays a role in the development of neural damage of hepatic origin. Most likely, similarly to diabetes mellitus, vascular changes contribute to the development of neuropathy in patients with chronic liver diseases. PMID- 11778352 TI - Physical activity in first-degree relatives of breast cancer patients. AB - This study sought to evaluate physical activity in women at moderate risk for breast cancer, the correlates of engaging in regular physical activity, and whether physical activity relates to psychological well-being. The results revealed that 55% of women were regularly active. Logistic regression models indicated that positive affect was associated with increased and negative affect was associated with decreased overall and leisure activity. Older, married, and employed women were more likely to engage in household/occupational activity, whereas women who perceived their risk for breast cancer as high were less likely. More educated women and those with higher perceived risk were more likely to engage in leisure activity, and married women were less likely. These results suggest a need to increase activity levels in women at moderate risk for breast cancer, provide variables upon which interventions can be tailored to promote activity, and point to psychological benefits of activity in this population. PMID- 11778355 TI - [Gastrointestinal stromal tumors. Observations on the basis of 29 cases]. AB - 42 gastrointestinal mesenchymal tumors are analyzed by the authors with characterization of immunohistochemistry and DNA study. Out of 42 tumors, 29 GIST 3 leiomyoma, 4 leiomyosarcoma, 3 benign schwannoma, 1 soliter fibrous tumor, 1 inflammatory myofibroblastic tumor and 1 benign haemangiopericytoma were found. All 29 GIST but two could be characterized by c-kit (CD-117) and CD-34 positivity independently weather they displayed focal neurogenic and/or myogenic immunomarkers. In GIST group, 10 cases were benign, 6 borderline and 13 malignant. All benign cases were euploid by DNA study, the malignant tumours were highly aneuploid. Concerning the borderline GIST group by morphology, the aneuploid DNA content may speak for malignant biological behavior, and the diploid DNA content in low grade malignant GIST by morphology may speak for better outcome in the malignant group. There is a discussion about the nomenclature of this morphological group, about the role of the c-kit gene and the necessity of the immunohistochemistry and DNA content determination. PMID- 11778356 TI - [First attempts in preimplantation genetic diagnosis: genetic analysis]. AB - Preimplantation genetic diagnosis is a new approach for the prevention of genetic disorders, which provides a healthy pregnancy avoiding the need for its possible termination. The combination of in vitro fertilization techniques and single cell molecular genetic diagnosis allows only unaffected embryos to be selected for transfer to the uterus. It is an acceptable alternative of prenatal diagnosis for certain couples. Here we report our first attempts in the application of fluorescent PCR for sex determination and the detection of the delta-F508 mutation in human blastomeres. We modelled clinical PGD situations as we performed sex determination on 23 preembryos. Sex determination was successful is 20 preembryos (83%). We performed the detection of the delta-F508 mutation on 23 preembryos, which was successful in 20 preembryos (87%). Our experience suggests, that the established fluorescent PCR analysis is a reliable method for PGD, which enables us to apply it for clinical preimplantation genetic diagnosis. PMID- 11778357 TI - [Scientometrics and publishing in Hungarian medical science. Ethical and technical issues]. AB - The authors present an account of the main ethical and technical aspects relating to the measurement of medical publication activities and the compilation of publications lists. It is demonstrated that the Anglo-American scientometric system (Institute for Scientific Information, USA) is currently gaining stable ground in Hungary. At the same time, however, there continues to be a place for a national publication index used to assess Hungarian-language publication activity, for the two systems conveniently supplement one another. The criterion system of medical publishing established by the International Committee of Medical Journal Editors (ICMJE) is described in detail, and is recommended for wide-ranging application in Hungary. PMID- 11778358 TI - [Cataract and refractive surgery in Hungary at the turn of the Millennium]. AB - A survey of cataract-, and refractive surgery carried out around the Millennium presents the habits, styles and results of the Hungarian surgeons. There is a significant trend for transition to phacoemulsification procedure, 38 per cent of all cataract surgeries have been carried out with this most modern procedure, and 4/5 of the operating institutes possesses the equipment needed for this operation. The refractive surgeries in Hungary have been carried out in 11 private institutes. The number of these procedures are in close relation with the level of living standards. PMID- 11778359 TI - [Otorhinolaryngeal and phonation aspects of gastroesophageal reflux disease]. AB - Experts dealing with patients of chronic upper and lower airway disorders have drawn a lot of interest in the last decades to gastrooesophageal reflux disease (GORD). Nowadays it is obvious that 'occult GORD' may be an aetiological factor in this group of patients. GORD may has a role in lot of organic laryngeal diseases and functional voice disorders. Symptoms are triggered by gastric content refluxed into the oesophagus, which cause irritation and inflammation. At laryngeal and phoniatric examinations gastrointestinal signs might remain hidden behind chronic cough, hoarseness and globus sensation. Authors summarise the diagnostic and therapeutic possibilities of GORD and its typical laryngeal and phoniatric manifestations. Although the first step is medication of GORD, it might come to surgical intervention of the laryngeal alterations, sometimes followed by voice therapy as well. Authors draw attention to patients after laryngectomy, whose voice rehabilitation therapy is extremely hindered by medical therapy resistant GORD. These patients may benefit of anti-reflux surgery. PMID- 11778360 TI - [Molecular pathogenesis of oral candidiasis (candidosis)]. AB - Candida species are the most important pathogenic fungi in the oral cavity with the predominance of Candida albicans. In this review the authors summarise the most important cell-surface bound pathogenical factors such as fibrinogen, fibronectin, thrombin, collagen, laminin and vitronectin-binding proteins and extracellular virulence enzymes of Candida albicans and some microbiological aspects of oral candidiasis (candidosis). Adherence to both artificial and mucosal surfaces is mediated by hydrophobic interactions and by ligand-receptor attachment. Surface bound proteins on Candida cells bind to mucosal surface proteins. Broad spectrum antibacterial treatment liberates binding sites for Candida colonisation by means of reducing the number of bacterial normal flora in the oral cavity. Non immune humoral factors such as iron, lysosyme, hystidine rich-polypeptides, lactoferrin, lactoperoxidase and immune globulins such as s IgA, moreover, elements of cellular immunity, especially polymorphonuclear leucocytes contribute to preventing the establishment of Candida infection. A disbalance in these constituents may result in colonisation and biofilm production of Candida. The biofilm consist of serum proteins mainly fibrin, desquamated epithelial cells, dead leukocytes, living and multiplying candida cells, pseudohyphae and extracellular matrix excreted by candida cells. Living candida cells are deeply embedded in the biofilm, thus protected from defence mechanisms of the host. Continuous destruction of mucosal surfaces beneath the biofilm may create a portal of entry for systematic candidal infections. PMID- 11778361 TI - [Viral screening of organ donors and human cytomegalovirus seroprevalence in the Hungarian population]. AB - The authors investigated 998 organ-donors for Human cytomegalovirus seroprevalence. The donors were divided into three age-groups. In organ-donors the seroprevalence was found to be 84%. A study was also conducted on a fourth group consisting of 200 residents from an old-age home. The youngest donor was 2 years of age, the eldest old-age home resident was of 92 years. The examined persons represent the hungarian population. It was found that as the result of the investigation of all 1198 subjects, the Human cytomegalovirus overall seroprevalence in Hungary is 86%. The age specific prevalence increases starting from 73% in the first group (2 to 20 years old) to 99% in the fourth group (71 to 92 years old). This has indicated that most of the population acquired the primary infection in the childhood or during early adulthood. According to these results the authors resumed that in Hungary the Human cytomegalovirus seroprevalence is high. This would cause problems when a seronegative organ recipient needs an organ transplantation. Between males and females a significant difference of Human cytomegalovirus seroprevalence was found: 89% of females were seropositive in contrast to 81% of males (p < 0.05). The organ-donors were also examined for the presence of HBsAg, anti-HCV and anti-HIV. 1.8% of donors were HbsAg positive, 0.9% were anti-HCV positive and 1 person was anti-HIV positive, but these results weren't verificated. PMID- 11778362 TI - [Porphyria cutanea tarda and hepatitis C virus]. AB - The development of clinically overt porphyria cutanea tarda (PCT) can be attributed to joint effects of genetic predisposition and environmental factors. Regarding exogen factors, studies from several countries published in the last years gave an account of significantly higher frequency of chronic hepatitis C virus (HCV) infection in PCT patients compared to the normal population. At the Department of Dermatology of University of Debrecen the prevalence of positive anti-HCV antibodies has been found in approximately 55% of PCT patients diagnosed from 1990 to 1999, which is comparable to the average prevalence rate seen in Southern-European countries. The majority of male patients were anti-HCV positive and consumed regularly alcohol, whereas every female patient had taken contraceptives. Liver enzymes were only slightly elevated in the majority of the patients and liver biopsy had to be performed only in three patients duo to chronic hepatitis. Our findings emphasise how important the screening of PCT patients for anti-HCV antibody considering that it might be important quo ad vitam for young men. PMID- 11778363 TI - [Familial hypophosphatemic rickets]. AB - Familiar hypophosphatemic rickets (FHR) is characterized by isolated defect of renal phosphate reabsorption, hypophosphataemia, rickets and poor growth. In untreated cases parathyroid hormone and calcitriol levels are normal. FHR is caused by mutations of the PHEX gene encoding a zinc-binding metalloprotease enzyme. PHEX is expressed in bones and the parathyroid gland but not in the kidney. The gene product is involved in the inactivation of a phosphate regulating hormone (phosphatonin). The presence of this hormone through unknown mechanisms decreases the sodium-dependent phosphate cotransporter in the kidney resulting in impaired phosphate transport. In addition the PHEX gene product exerts autocrine and paracrine effects on the bone. Despite recent advances in the understanding of the pathomechanism, treatment of FHR is still symptomatic. It consists of active vitamin D analogues and oral phosphate supplementation. Nephrocalcinosis is a well-known, usually non-progressive side effect of the conventional therapy. As shown by pilot studies, poorly growing children with FHR may benefit from the positive effect of human recombinant growth hormone (rhGH). However, rhGH treatment could aggravate the already existing tendency to disproportionate growth resulting in the overgrowth of the trunk. The disturbed phosphate homeostasis persists during the whole life span of the FHR patients. It is therefore essential to provide lifelong care, to prevent late skeletal and dental consequences or to treat them if already established. That care should be done by the teamwork of the pediatrician, internist, orthopedist, dentist and the psychologist. PMID- 11778364 TI - [Clinical, microbiological and therapeutic aspects of oral candidiasis (candidosis)]. AB - Exogenic, prosthetical and endogenic factors that may influence and facilitate fungal infections of the oral cavity are summarized. The clinical classification of the oral candidiasis is based on the criteria accepted in the international literature. The main points for the classification are the clinical appearances, the histopathological alterations and the possible manifestation of an underlying disease. In the last part of the review a brief summary is given on the antifungal agents such as polyenes, azole-derivatives and DNA analogs available for candidiasis. PMID- 11778365 TI - [Limiting factors of aerobic capacity]. AB - High aerobic capacity is necessary to maintain high intensity, wholebody physical exercise for several minutes. Any steps in the chain of the oxygen delivery and mitochondrial consumption can be a rate-limiting factor of the aerobic functional system. Many examples in the field of the pathology and of the performance physiology demonstrate limiting functions in the elements of this function. Central factors (cardiac output, gas exchange in the lungs, oxygen transport capacity of the blood) and the oxidative capability of the muscle play a probably well integrated role in functioning of the system. A couple of interventions- increase by training, adaptation to the circumstances, medicaments etc are available to restore the failing functions which serve as the physiologic basis of the rehabilitation. PMID- 11778366 TI - [Primary resection of obstructive left-sided colon and rectal tumors without intraoperative lavage]. AB - Of the study is to show the results of early postoperative period of left-sided large bowel obstruction (LBO) and methods of decompression without colonic lavage and primary resection. Retrospective analysis of 28 patients admitted to the Surgical Department with LBO between years 1996 and 2000 were treated with ortograde decompression, and primary resection without on table colonic lavage. The surgical method, complications and mortality are pointed out. The patients average age were 71 +/- 9.7 years and only one was free of comorbidity. The average time of operative interventions was 116 +/- 42 minutes. 9 patients out of 28 had rectum cancer their anastomosis were made by instrumental way and the others by hand. The bowel movement was restored (in 89%) on the fourth day of operation. Surgical complications were observed at 3/28 patients (10.7%), and non surgical complication at three patients. Mortality rate 3.5%, one patient was lost. The average hospital stay was 12 +/- 5 days, 70% of the patients were at home within 11 days. The emergency surgical treatment of left-sided colonic obstruction caused by cancer treated by ortograde decompression and primary resection without colonic lavage is a safe method in experienced surgeon hand. The patients have a short recovery period and better quality of life. PMID- 11778367 TI - [Pettenkofer, the (not unerring) pope of public health]. PMID- 11778368 TI - ["Dioscorides writes, Matheolus proves"--P.A. Mattioli botanist-physician was born 500 years ago]. PMID- 11778369 TI - The terrorists here at home. PMID- 11778370 TI - Suffer the children. PMID- 11778371 TI - The "other" tragedy. PMID- 11778372 TI - The cell wars begin. PMID- 11778373 TI - A better way to give a heart. PMID- 11778374 TI - Just cloning around. PMID- 11778375 TI - The massively bleeding patient. AB - The resuscitation of the massively bleeding patient may seem superficially to be successful once the patient's vital signs have stabilized. The restoration of stable vital signs, however, does not confirm two critical elements of a thorough physiologic resuscitation: that there is truly adequate delivery of oxygen to all tissue beds and that physiologic disturbances that may have occurred because of massive transfusion during the resuscitation process have resolved. With respect to the adequacy of oxygen delivery, the current clinical endpoints, including mixed venous oxygen saturation, cardiac output, and serum lactate, reflect global perfusion and not regional oxygenation. Of these global measures, serum lactate is currently the best indicator as to whether some circulatory beds remain inadequately perfused. Serum lactate should be followed, and, in the event that elevated levels persist, measures to augment oxygen delivery (e.g., increasing cardiac output, hemoglobin concentration, oxygen saturation) should be undertaken. Gastric tonometry provides a method for specific examination of the splanchnic circulation. The current measurement techniques, however, require steady-state conditions and make it impractical in many physiologically dynamic situations. The physiologic disturbances associated with massive resuscitation (e.g., hyperkalemia, hypocalcemia, hypomagnesemia, hypothermia) should be anticipated. Coagulation disturbances occur, especially when massive transfusion is accompanied by hypotension, hypothermia, or acidosis. Coagulation parameters should be measured with the loss of each one half of blood volume or after each 30-minute interval, whichever occurs first. Evaluation at blood volume intervals is relevant to the development of a strictly dilutional coagulopathy. The development of DIC, occurring because of tissue factor exposure or acidosis, however, is related more to the time lapsed than to the absolute volume lost or replaced. PMID- 11778376 TI - Myocardial ischemia. Monitoring to diagnose ischemia: how do I monitor therapy? AB - Diagnosis of myocardial ischemia requires integration of ECG, pulmonary artery pressures, and TEE data. ST depression of 1 mV or elevation of 2 mV remains the mainstay of diagnosis of ischemia. Increases of pulmonary artery pressures of 5 mm Hg are common but not reliably diagnostic of ischemia. Transesophageal echocardiography is the most sensitive monitor of ischemia, where the spectra of SWMA evolve. Diastolic dysfunction (elevations in LVEDP) is a more sensitive marker of ischemia, but requires measurement of several Doppler patterns. After diagnosis, treatment should include optimization of hemodynamics (beginning with beta-blockers and nitrates), anesthesia, and oxygen-carrying capacity (e.g., normothermia, oxygen saturation, hematocrit more than 28%). PMID- 11778377 TI - Monitoring for suspected pulmonary embolism. AB - It is fortunate that serious embolic phenomena are uncommon because, with the exception of neurosurgery in the sitting position and cardiac surgery, thoracic echocardiography and the precordial Doppler device, the most sensitive indicators of embolism, are seldom used. Vigilance is required of the anesthesiologist to recognize the rapid fall in end-tidal PCO2, the usual first indicator of a clinically significant PE. Any sudden deterioration in the patient's vital signs should include embolism in the differential diagnosis, particularly during procedures that carry a high risk of the complication. PMID- 11778378 TI - Anaphylaxis. What is monitored to make a diagnosis? How is therapy monitored? AB - Anaphylaxis is one of the most life-threatening emergencies that can occur in the perioperative period. Multiple agents can be responsible, and nonallergic reactions can mimic anaphylaxis. Developing a therapeutic plan for the acute therapy of anaphylaxis is important. Prompt recognition with appropriate and aggressive therapy can help avoid a disastrous outcome. PMID- 11778379 TI - Cardiac arrest and monitoring. AB - Initial assessment to determine pulselessness, monitoring the status of the patient, and the effectiveness of resuscitation efforts are integral parts of cardiopulmonary resuscitation. This article focuses on aspects of monitoring during cardiopulmonary resuscitation: electrocardiography and assessment of the adequacy of chest compressions. PMID- 11778380 TI - Performing a complete transesophageal echocardiographic examination. AB - Transesophageal echocardiographic (TEE) examination is a powerful and informative cardiac monitor and an important diagnostic tool for use during cardiac surgery. This article reviews how to perform a comprehensive TEE examination on a patient in the operating room and the important clinical uses of TEE during critical events. PMID- 11778381 TI - Perioperative hypoxia. The clinical spectrum and current oxygen monitoring methodology. AB - When searching for the source of hypoxia, the anesthesiologist and intensivist one served best by treating the patient in an organized approach--beginning with the environmental and pulmonary sources, searching for anemic and circulatory sources, and finally ruling out the less common histocytic causes. When treating hypoxia, the first maneuver should be to administer oxygen, ensure airway, ventilation, and circulation (the ABCs of basic life support). Further monitoring is addressed at global assessments and specific organ systems (especially in high risk patients or during high-risk procedures). The ability to directly measure the oxygenation, blood flow, and function in each individual organ of the body is not yet available. Efforts are advancing in the ability to measure the function of important tissue beds, such as the brain and splanchnic circulation. In this regard, Table 5 provides a summary of the spectrum of monitoring technology available for various organs. PMID- 11778382 TI - Verification of endotracheal tube position. AB - The goals of tracheal intubation are to place the tube in the trachea and to position the tube at an appropriate depth inside the trachea. Various clinical signs and technical aids are described to verify tracheal intubation and to diagnose esophageal intubation. Many of these methods fail under certain circumstances. Not all these methods can be applied in every intubation, but it is essential that the clinician involved in tracheal intubation have the necessary airway management skills, perform these tests accurately, and interpret the results correctly. Prioritization of these tests depends on many factors, including familiarity, availability of monitors, and the location of intubation. Viewing the tube passing between the cords during direct laryngoscopy and visualization of the tracheal rings and carinae with a fiberoptic scope after intubation are the only fullproof methods of confirming tracheal intubation. In the nonarrested patient, carbon dioxide monitoring quickly can differentiate tracheal from esophageal intubation. In the arrested patient, however, carbon dioxide monitoring can be unreliable, although it can be useful as a prognostic indicator of the efficacy of resuscitation. Devices such as [figure: see text] the self-inflating bulb and esophageal detector device may be more useful in patients with cardiac arrest, but they also can yield false results. Placing the distal tip of the tube in the middle of the trachea can be accomplished by positioning the upper end of the cuff 2 cm below the cords during direct laryngoscopy or by placing the distal tip of the tube 4 cm above the carinae with the aid of a fiberoptic scope. The position of the tube always should be verified by clinical assessment (e.g., auscultation). If direct visualization cannot be done, referencing the marks on the tube, transillumination techniques, or cuff maneuvers can be helpful. In the emergency and critical care settings, a chest radiograph easily can detect malpositioned tracheal tubes that may not be detected by routine clinical assessment. Other techniques (e.g., use of fiberoptic scopes, cuff maneuvers, transillumination) can decrease the need for frequent chest radiographs. Based on available information, two algorithms are proposed: one for emergency intubation (Fig. 9) and the other for verification of tracheal tube position in elective intubation (Fig. 10). These algorithms are designed [figure: see text] to assist the clinician and should not be substituted for clinical judgment. Under no circumstances should clinical signs be ignored in the presence of conflicting information from monitors and technical aids. PMID- 11778383 TI - Oliguria. A sign of renal success or impending renal failure? AB - Limiting renal impairment begins with identifying patients at increased risk for renal dysfunction (monitoring of renal function is important in these patients) and understanding the physiology of urine formation, the influence of anesthetic drugs, and intraoperative events on the physiology and pathophysiology of renal function. The fundamental principles emphasized in this article include avoidance of hypovolemia or renal hypoperfusion (e.g., hypotension, decreased cardiac output) in patients at risk (because of pre-existing disease or the nature of the operative procedure) and limitation of toxins that might jeopardize residual renal function. Direct monitors of renal well-being are still in the rudimentary stage of development. Indirect measures of renal function (CVP, MAP) are used on a minute-to-minute basis. The clinical measurement of urine output still is relied on when evaluating renal function over longer time intervals. Currently, only one drug (N-acetylcysteine) improves renal outcome after a high-risk procedure (radiocontrast administration) prophylactically. Manipulation of autorenal regulatory vasodilators (e.g., nitric oxide, PGE2) and vasoconstrictors (e.g., endothelin, vasopressin, angiotensin II) may prove helpful in the future. Currently, maintenance of adequate intravascular volume, MAP, and cardiac output are the most important renal protective measures an anesthesiologist can provide to preserve renal function high-risk patients. PMID- 11778384 TI - Arterial blood gas and pH analysis. Clinical approach and interpretation. AB - Arterial blood gas and pH analysis are performed during anesthesia or critical care medicine for (1) assessment of acid-base balance, (2) assessment of pulmonary oxygenation of arterial blood, and (3) assessment of alveolar ventilation by measurement of arterial blood PCO2. Total physiologic and alveolar dead spaces are evaluated by comparing the alveolar PCO2 with the mixed expired and mixed alveolar PCO2, respectively. This article provides a clinical approach and interpretation of arterial blood gas and pH analysis. PMID- 11778385 TI - Clinical approach to acid-base analysis. Importance of the anion gap. PMID- 11778386 TI - Neuromuscular blockade. Inadvertent extubation of the partially paralyzed patient. AB - Residual neuromuscular block is common after the use of neuromuscular blocking drugs during anesthesia. Although careful reversal [table: see text] techniques usually result in adequate return of neuromuscular recovery, sometimes it is not possible to achieve full recovery of neuromuscular block. Ventilatory support and maintenance of a patent airway are required until recovery can be demonstrated. In those situations, in which some TOF fade is still obvious, the anesthesiologist should consider retaining the endotracheal tube in position; it is not a sign of failure to return a patient whose trachea is still intubated to the postanesthesia care unit. The inadvertent extubation of patients who are partially paralyzed results in increased postoperative morbidity. PMID- 11778387 TI - Spinal cord monitoring: somatosensory- and motor-evoked potentials. AB - Monitoring myogenic motor EPs after transcranial electrical stimulation is effective in detecting spinal cord ischemia. During thoracoabdominal aortic aneurysm surgery, this technique is sufficiently rapid to allow timely interventions aimed at correcting ischemic conditions and preserving spinal cord blood flow. If strategies are applied to protect the spinal cord during thoracoabdominal aortic aneurysm repair (e.g., distal bypass, cerebrospinal fluid drainage, reattachment of segmental arteries), motor EP monitoring should be included in this protocol to improve neurologic outcome further. Although SSEPs provide information regarding the adequacy of spinal cord blood flow, monitoring SSEPs during thoracoabdominal aortic aneurysm repair has serious limitations. The response time is too slow to be of practical use. SSEPs also do not provide information regarding anterior horn motor function and supply, whereas the motor neurons in the anterior horn are most likely to sustain ischemic injury. PMID- 11778388 TI - Bispectral index monitoring. AB - The Bispectral Index (BIS) is a newly processed electroencephalogram parameter that was specifically developed to measure the hypnotic effects of anesthesia. Results from volunteer studies demonstrate that BIS correlates well with clinical assessments of sedation induced by sedative-hypnotic drugs. Clinical utility studies have shown also that BIS monitoring allows for better titration of anesthesia, resulting in lower hypnotic drug use and improved recovery. The data suggest that improved anesthetic titration with BIS provides sufficient clinical and economic benefits to justify its routine use. This article summarizes the clinical development and validation of BIS and describes how BIS monitoring can be used to improve anesthetic outcomes. PMID- 11778389 TI - Sadistic personality disorder in perpetrators of human rights abuses: a South African case study. AB - Although state-sponsored human rights abuses have long been commonplace, the psychological profiles of perpetrators are not well delineated. This article examines the utility of the diagnosis of sadistic personality disorder (SPD) in explaining the commission of atrocities. The history of, and controversies surrounding, SPD are briefly reviewed. Using a case study from the amnesty trials of the Truth and Reconciliation Commission (TRC) in South Africa, the relevance of the SPD diagnosis for an infamous perpetrator of political violence is debated. Sources of data include the perpetrator's autobiography, transcripts from the amnesty trial, and Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II; First, Spitzer, Gibbon, & Williams, 1994) ratings provided by four people who had contact with the perpetrator during his trial. The authors provide arguments for and against the use of the SPD diagnosis in this case and in similar contexts of perpetration. It is proposed that neither psychological reductionism nor social reductionism can adequately account for the motivations of political perpetrators, and an integrative approach to the understanding of perpetrators is advocated. Implications for diagnostic criteria are discussed. PMID- 11778390 TI - The development of a psychodynamic treatment for patients with borderline personality disorder: a preliminary study of behavioral change. AB - This study examines the effectiveness of a modified psychodynamic treatment called Transference Focused Psychotherapy (TFP) designed specifically for patients, with borderline personality disorder (BPD). Twenty-three female patients diagnosed with DSM-IV BPD began twice-weekly TFP. Patients were assessed at baseline and at the end of 12 months of treatment with diagnostic instruments, measures of suicidality, self-injurious behavior, and measures of medical and psychiatric service utilization. Compared to the year prior to treatment, the number of patients who made suicide attempts significantly decreased, as did the medical risk and severity of medical condition following self-injurious behavior. Compared to the year prior, study patients during the treatment year had significantly fewer hospitalizations as well as number and days of psychiatric hospitalization. The dropout rate was 19.1%. This uncontrolled study is highly suggestive that this structured and manualized psychodynamic treatment modified for borderline patients shows promise for the ambulatory treatment of these patients and warrants further study. PMID- 11778391 TI - Sexual trauma and personality: developmental vulnerability and additive effects. AB - Two types of sexual trauma, sexual abuse in childhood and rape in adulthood, were investigated in terms of possible effects on personality. Four groups of participants were studied: women who had experienced sexual abuse in childhood, women who had experienced rape as adults, women who had experienced both of these sexual traumas, and a control group of women who had experienced no sexual trauma. Personality functioning was assessed using the Dimensional Assessment of Personality Pathology. Groups who had experienced childhood sexual abuse displayed the highest degree of personality disturbance; however, the additive effects of repeated sexual trauma were limited. These findings may reflect the outcome of specific adversity in childhood on the psychobiological constructs underlying personality. PMID- 11778392 TI - Emotional, physical, and sexual maltreatment in childhood versus adolescence and personality dysfunction in young adulthood. AB - The current study examined the unique relations of childhood and adolescent maltreatment (emotional, physical, and sexual) with DSM-III-R personality disorder (PD) dimensions in a sample of undergraduates. The results suggested that reported levels of childhood sexual maltreatment were uniquely related to six of the 11 PD dimensions examined. In contrast, reported levels of adolescent emotional maltreatment were uniquely related to only three PD dimensions and reported levels of adolescent physical maltreatment were uniquely related to only one PD dimension. Thus, whereas reported levels of adolescent emotional and physical maltreatment demonstrated some specificity to the various kinds of personality dysfunction, reported levels of childhood sexual maltreatment appeared to be related to more generalized personality dysfunction in young adulthood. PMID- 11778393 TI - Predicting self-damaging and suicidal behaviors in female borderline patients: reasons for living, coping, and depressive personality disorder. AB - The aims of this study are to examine (1) whether reasons for living predict self damaging and suicidal behaviors, (2) the associations of reasons for living with coping strategies and depressive personality disorder (PD), and (3) the unique predictive validity of reasons for living in a multivariate predictor model. Reasons for living (RFL), coping strategies, and depressive personality disorder were measured at baseline in 38 patients who met DSM-IV criteria for borderline personality disorder (BPD). Frequency of self-damaging and suicidal behaviors in the 6-month period following baseline was measured prospectively at 3- and 6 month follow-ups. The RFL has only one subscale that predicts parasuicidal behaviors (i.e. Survival and Coping Beliefs [SCB]). Participants who scored low on this subscale were 6.8 times more likely to exhibit self-damaging and suicidal behaviors in the follow-up period than their high-scoring counter-parts. However, SCB was substantially correlated with the coping strategies "reassuring thoughts," "active coping," and "palliative reaction pattern," as well as with depressive personality traits. In a multivariate model, the predictive power of SCB appeared to be accounted for by reassuring thoughts and depressive PD. Coping scales might be preferable over the RFL as a predictor of self-damaging and suicidal behaviors in borderline patients. PMID- 11778394 TI - Exploring the latent structure of the Perceptual Aberration, Magical Ideation, and Physical Anhedonia Scales in a German sample. AB - The schizotypy model proposed by Meehl (1990) assumes a discontinuous distribution of schizophrenia liability. The "schizogene" is thought to determine if one is at risk for psychosis (i.e., whether one is a member of the taxon or its complement, which are considered to be the two latent classes). Using a German non-student sample (n = 809) we wanted to (1) replicate the results of prior research pertaining to the latent structure and base rate of schizotypy assessed by the Perceptual Aberration Scale (PER; Chapman, Chapman, & Raulin, 1978), and (2) investigate whether the same holds true for two other prominent psychometric indices, the Magical Ideation Scale (MI; Eckblad & Chapman, 1983) and the Physical Anhedonia Scale (PhA; Chapman et al., 1976), if one uses the same kind of analysis--the MAXCOV-HITMAX analysis based on subsets of items (Meehl, 1973). Pertaining to PER and PhA, our results are in accordance with prior research showing a latent class structure and a base rate of about 12% for schizotypy. However, for MI, there was no evidence of a taxonic structure. Possible reasons for MI's negative results are discussed as well as the role of the concept "anhedonia." PMID- 11778395 TI - The factor structure of the Personality Assessment Inventory-Borderline Features (PAI-BOR) Scale in a nonclinical sample. AB - We evaluated the fit of Morey's (1991) proposed 4-factor structure on Personality Assessment Inventory-Borderline Features Scale (PAI-BOR; Morey, 1991) items in a sample of approximately 5,000 nonclinical participants. The proposed model did not fit the data well. Results from a series of exploratory and confirmatory factor analyses suggested that a 6-factor model provided the best fit to the PAI BOR item covariances. PMID- 11778396 TI - Early maladaptive schemas of personality disorder subtypes. AB - This investigation attempted to examine the cognitive schemas of five distinct clusters that emerged from a cluster analysis of the personality disorder scales of the Millon Clinical Multiaxial Inventory-II (Millon, 1987). Specifically, the degree to which early maladaptive schemas, as measured by the Cognitive Schema Questionnaire-Short Form (Young, 1994), could correctly identify empirically derived patterns of personality disorders was examined. Between-cluster differences centered on five personality components and five schemas. Discriminant analyses revealed two significant functions composed of cognitive schemas, which correctly identified 61.2% of the entire sample in terms of cluster group membership. The total proportion of variance in the two significant functions associated with cluster group differences was 76.8%. Findings are discussed in relation to the domain theory of personality disorders posited by Millon and Davis (1996). PMID- 11778397 TI - Uniformed pediatricians and humanitarian assistance. PMID- 11778398 TI - Issues for military women in deployment: an overview. AB - The stresses of deployment affect both sexes, but some are either mildly or markedly different for women. These include certain female health and gynecological issues, nursing, and pregnancy. Separation from small children, isolation, the possibility of sexual assault, and risks of combat or being taken hostage are concerns for both genders. All of these issues should be addressed before and during deployment to ensure optimal individual and unit functioning and improve retention. Gynecological infections, redeployment for abnormal Papanicolaou smears, and pregnancy while on deployment can be avoided with proper hygiene and planning. There are resources available in pamphlet form, electronically, and on CD-ROM to help prepare service members, leaders, and health care personnel. Improvements in the ability to maintain personal hygiene and to communicate home should benefit both sexes. PMID- 11778399 TI - Operational experiences during medical residency: perspectives from the Walter Reed Army Medical Center Department of Medicine. AB - The preparation of military primary care physicians for practice in operational environments has taken on greater importance during the past decade. The Department of Defense military-unique curriculum identifies the elements that should be incorporated into residency training programs to accomplish comprehensive training in operational matters. We describe efforts to integrate the military-unique curriculum into internal medicine residency, including obstacles encountered, so that other programs may learn from our experience. PMID- 11778400 TI - Predicting Farnsworth Lantern success with a six-plate series of the Ishihara pseudoisochromatic plates. AB - The Farnsworth Lantern (FALANT) is the definitive color vision test for the Navy, Marine Corps, and Coast Guard. It is also the definitive color vision test for aviation personnel in the Army. Results from it are also accepted by the Federal Aviation Administration. For various reasons, it is desirable to have an alternative test that can predict success (i.e., a passing score) on the FALANT. In 1991, it was shown that a 14-plate series of Ishihara pseudoisochromatic plates could predict FALANT success provided the proper passing criteria was chosen. Interest has arisen regarding whether or not a 6-plate series of Ishihara plates can predict FALANT success. A study was undertaken to answer this question. It appears that a 6-plate series of Ishihara pseudoisochromatic plates can predict FALANT success. PMID- 11778401 TI - Allogeneic bone marrow transplantation at Wilford Hall U.S. Air Force Medical Center: 1987-1999. AB - Wilford Hall Medical Center (WHMC), at Lackland Air Force Base in San Antonio, Texas, is the only center within the U.S. Department of Defense at which allogeneic bone marrow transplantation (BMT) is performed. From the inception of the BMT program in 1987 through February 1999, 286 military health care beneficiaries have undergone human leukocyte antigen-matched related donor allogeneic bone marrow transplantation for hematologic disorders. We conducted a retrospective chart review to analyze the outcomes of all allogeneic BMT procedures performed at WHMC through February 1999. Our analysis revealed that allogeneic BMT outcomes compared favorably with those reported by the International Bone Marrow Transplant Registry. The results of this study support the continued designation of the Fisher Bone Marrow Transplant Center at WHMC as a specialty treatment service within the Department of Defense. PMID- 11778402 TI - Selective serotonin reuptake inhibitors and isoniazid: evidence of a potential adverse interaction. AB - BACKGROUND: Recognizing a potential interaction between isoniazid (INH), a weak monoamine oxidase inhibitor, and serotonin reuptake inhibitors (SSRIs), we assessed medication discontinuation rates in human immunodeficiency virus infected individuals taking an SSRI, INH, or both. METHOD: We retrospectively reviewed treatment records to determine if patients on an SSRI, INH, or both completed drug therapy in accordance with a treatment plan (e.g., 12 months of INH therapy). Patients on both medications constituted the study group; patients taking either an SSRI or INH alone constituted comparison groups. RESULTS: There were no significant differences between the groups based on age, gender, CD4%, or CD4 count. Seven of the 10 patients (70%) in the study group discontinued therapy, which was significantly greater than the 2 of 14 (14%) in the SSRI group (P = 0.01) and the 4 of 18 (22%) in the INH group (p = 0.02) who discontinued therapy. CONCLUSION: Medication discontinuation rates for patients prescribed an SSRI coincident with INH were significantly higher than for individuals prescribed these medications separately. These differences cannot be accounted for on the basis of age, gender, or CD4%, but they may be attributable to increased side effects caused by interactions between these medications. PMID- 11778403 TI - Creutzfeldt-Jakob disease and blood transfusions: a meta-analysis of case-control studies. AB - A meta-analysis of five published case-control studies that examined the association between previous blood transfusions and Creutzfeld-Jakob disease was performed. The results demonstrated that controls were more likely (p < 0.001, odds ratio = 1.56, 95% confidence interval, 1.22-1.98) to have received previous blood transfusions (18.7%) than Creutzfeld-Jakob disease patients (12.9%), suggesting that selection bias of the control populations had occurred. PMID- 11778404 TI - Disease and nonbattle injury related to peacekeeping operations in South America: summary patient care statistics for CABANAS 2000. AB - Peacekeeping operations and training for peacekeeping missions currently require far more time and personnel from our armed forces than previously. Although literature exists describing mortality, disease and nonbattle injury (DNBI), and medical support for peacekeeping operations in Europe, Africa, the Caribbean, and the Far East, none was found concerning operations and training for peacekeeping in South America. The present retrospective study presents an analysis of DNBI for forces participating in CABANAS 2000, an eight-nation peacekeeping training exercise held in Argentina. The mean DNBI rate for the 6-week period was 4.1 cases/100 personnel/week. Frequently cited causes for service member presentations for medical treatment were respiratory disease (43%), orthopedic disorders and injuries (25.9%), other miscellaneous medical conditions (8.5%), dermatologic complaints (6.9%), and diarrhea and intestinal complaints (6.5%). These findings indicate that peacekeeping operations and training in South America are relatively safe. PMID- 11778405 TI - Management of varicocele in military obligatory service: Israel Defense Forces Medical Corps policy. AB - Varicocele is a well-known and highly prevalent medical problem in young obligatory service recruits. Still, there are many questions regarding its management. Is there a clear relation between varicocele and infertility? Can early varicocelectomy in young soldiers prevent future infertility? Is there a role for varicocelectomy in pain relief in physically active soldiers? And finally, what are the pros and cons of the open surgical, laparoscopic, or radiographic techniques in this specific population? Answering these questions should help military physicians in varicocele patients' care. It should also help decision makers to build cost-effective and evidence-based health policy. In this article, we review the literature regarding the controversies in the management of varicocele in young adults and delineate the current policy of the Israel Defense Forces Medical Corps. PMID- 11778406 TI - Terminal ballistics of the Russian AK 74 assault rifle: two wounded patients and experimental findings. AB - OBJECTIVE: To study the effects of the Russian AK 74 assault rifle missile (5.45 x 39 mm) on an experimental model and on two wounded patients. DESIGN: Experimental and clinical study. SETTING: Brodarski Institute, Marine Research and Special Technologies, Zagreb, Croatia, and General Hospital, Karlovac, Karlovac, Croatia. MATERIALS AND PATIENTS: Twenty gelatin blocks used as tissue stimulants and two patients with gunshot wounds caused by AK 74 assault rifle missiles. INTERVENTIONS: After being fired at, gelatin blocks were filmed with a high-speed television camera and radiographs were made of the blocks. Wounds of our patients were treated with minimal excision and drainage. MAIN OUTCOME MEASURES: The correlation between the wound profile method and our experimental model, and the correlation between the wound profile method and the wounds of the patients we treated. RESULTS: Bullets were not found to deform or fragment in tissue stimulant. The bullet path through the gelatin block was found to differ from the path predicted according to the wound profile method. CONCLUSION: Gelatin disruption in the initial 8 to 11 cm of the bullet path is minimal. Even the highest-velocity military missiles, like the AK 74 5.45 x 39 mm bullet, may cause only minimal tissue disruption in this initial part of tissue penetration. PMID- 11778407 TI - Psychological attributes of South African Navy Underwater Sabotage Device Disposal operators. AB - The first of two studies described here aimed to determine the extent to which psychological instruments could be used to describe the psychological profile of Underwater Sabotage Device Disposal (USDD) operators in the South African Navy. The Advanced Progressive Matrices, 16-Personality Factor Questionnaire (16PF), Self-Directed Search Questionnaire, and Rey Complex Figure Test were used. In this study, five 16PF factors appeared to be most descriptive of the sample. They were adventurous, assertive, self-assured, emotionally stable, and tough minded. These factors appeared appropriate when discussed from an environmental demand perspective. Occupational interests were realistic and social, and operators scored high on the Complex Figure Test. The second study aimed to determine the extent to which the 16PF could differentiate between USDD operators and other clearance divers. Two factors showed a significant difference between the two groups. The USDD operators were more adventurous and more assertive, which also appeared appropriate when discussed from an environmental demand perspective. PMID- 11778408 TI - U.S. Army dental emergency rates in Bosnia. AB - OBJECTIVE: Our objective is to report on overall dental emergency rates and rates by dental classification of a U.S. Army peacekeeping operation longer than 6 months in the year 2000. MATERIALS AND METHODS: This study was a retrospective cohort analysis of dental emergencies experienced by soldiers of the 3rd Armored Cavalry Regiment as a part of Stabilization Force VII. Before the deployment, all soldiers received dental examinations and the necessary dental treatment to make them class 1 or 2. A dental emergency was identified from field treatment records when a soldier presented to the clinic for a "sick call," emergency, or trauma visit. RESULTS: Retrospective review of the records identified 211 dental emergencies. Class 1 soldiers experienced 75 dental emergencies and class 2 soldiers experienced 136 emergencies. 3rd Armored Cavalry Regiment soldiers spent an average of 201.95 days deployed. The overall emergency rate was 156 dental emergencies per 1,000 soldiers per year. Class 1 and 2 rates were 121 and 185 dental emergencies per 1,000 troops per year, respectively. CONCLUSIONS: The results tend to confirm that dental emergencies continue to be a threat to overall readiness in deployed environments. Military planners need to ensure that the dental component of future forces are sufficient to care for the expected emergencies. PMID- 11778409 TI - Put more "bite" into health promotion: a campaign to revitalize health promotion in the Army Dental Care System. Part IV. Implementation. AB - During the course of 1998, the Army Dental Care System (ADCS), in collaboration with the U.S. Army Center for Health Promotion and Preventive Medicine, launched Put More "Bite" into Health Promotion, a campaign to revitalize health promotion in the ADCS. This article discusses implementation issues for health promotion campaigns. PMID- 11778410 TI - Pneumococcal vaccine to counter emerging infectious disease threat in the military. AB - Streptococcus pneumoniae causes severe morbidity and mortality worldwide and poses a significant threat to the health and readiness of U.S. military personnel. Although a vaccine to prevent pneumococcal infections has been available for almost 25 years, its use has been limited. Recently, increasing antibiotic resistance among S. pneumoniae strains has emerged, prompting health care professionals to reevaluate the benefit of administering pneumococcal vaccine. The Naval Health Research Center, in collaboration with professionals from numerous civilian and military organizations, has initiated a rigorous double-blind, placebo-controlled trial investigating the operational value of vaccinating young adults as they enlist in the military. PMID- 11778411 TI - Diverting loop colostomy for the treatment of refractory gastrointestinal bleeding secondary to radiation proctitis. AB - Chronic radiation proctitis is an uncommon and serious complication of radiotherapy for pelvic malignancies. It has been suggested that fecal stream diversion decreases bowel irritation, resulting in decreased rectal bleeding. We report on the outcome of patients after a diverting loop colostomy for the treatment of severe radiation proctitis. All consecutive patients with chronic proctitis treated with diverting loop colostomy for bleeding at one institution between October 1991 and June 1999 were studied. Four patients presented with rectal bleeding and diarrhea, and two patients had only bleeding. The mean dose of radiation received was 6,115.11 +/- 955.11 rad. Symptoms of chronic proctitis appeared at varying intervals of time after radiation, ranging from 14 months to 17 years. There were no operative complications. During follow-up (36 +/- 29 months), only one of nine patient continued to bleed. Four patients died during the study (cancer relapse, two patients; heart failure, one patient; one death was caused by severe radiation proctitis). Diverting sigmoid loop colostomy, when performed in properly selected patients with severe bleeding secondary to radiation proctitis refractory to medical management, is well tolerated and effective. PMID- 11778412 TI - Evaluation of an educational intervention for military tobacco users. AB - This study evaluated the short-term effect of a one-time tobacco hazard education intervention on tobacco use and intention to quit among military tobacco users. Of the 151 Army infantry soldiers who received the intervention, 60 (40%) participated in a 1-month follow-up survey. Respondents' reported pre intervention tobacco habits included 51% smoking, 22% smokeless tobacco use, and 27% both. A one-group, posttest-only design demonstrated a decline in tobacco use in more than half of tobacco users: 14% quit, and 37% decreased use. However, 46% stayed the same, and 3% increased use. A statistically significant difference in tobacco use existed among the three subgroups of tobacco users (p = 0.004). Smokeless-tobacco-only users were more likely to quit than smoking-only or combined users. Eighty percent had positive thoughts or actions toward quitting tobacco use after the intervention. Results suggest that a one-time tobacco education intervention can positively influence tobacco use in the short term and motivate tobacco users toward quitting. PMID- 11778413 TI - The Bremerton enrollment capacity model: an enrollment capacity model supporting the military health system optimization plan. AB - The Department of Defense has launched several initiatives to improve efficiency and quality of care in the military health system. The goal of empaneling 1,300 to 1,500 patients per primary care manager did not correlate well with Naval Hospital Bremerton's experience and did not accurately account for military specific requirements. The Bremerton Model Task Force was chartered to assess current business practices, identify areas for improvement, and develop a capacity model reflecting military readiness and residency training requirements. Methods included a 12-month review of patient visits and staff surveys of how providers spent their day, with time-and-motion analysis to verify assumptions. Our capacity results (average, 791 enrollees per primary care manager) demonstrated that objective measures at the local level do not support enrollment to Department of Defense-specified levels. Significant changes in "corporate culture" are necessary to accomplish the military health system goals. PMID- 11778414 TI - Medical follow-up of Persian Gulf War Veterans with severe medically unexplained fatigue: a preliminary study. AB - An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans. PMID- 11778415 TI - Twenty-year-old man with right arm swelling. PMID- 11778416 TI - Selective serotonin reuptake inhibitors in active duty military personnel. PMID- 11778417 TI - The role of the Department of Defense in domestic weapons of mass destruction consequence management. PMID- 11778418 TI - Medical consequences of biological warfare: the Ten Commandments of management. PMID- 11778419 TI - Meeting the threat of weapons of mass destruction terrorism: toward a broader conception of consequence management. AB - As the importance of psychosocial issues in domestic preparedness has come to be better understood, it has become evident that there are significant conceptual limitations in existing approaches to weapons of mass destruction consequence management. This article identifies six problems: (1) most understandings of consequence management focus on short-term issues with longer-term recovery issues receiving far less attention; (2) while psychological issues are beginning to be introduced, social issues are generally not addressed; (3) although more attention is being paid to mental health issues, scenarios that are predominantly psychosocial in their effects are not generally considered; (4) social and behavioral science insights are not adequately incorporated; (5) despite the further inclusion of psychological issues, the overall approach is not sufficiently integrated or interdisciplinary; and (6) although psychological issues are receiving more attention, fundamental macro-level issues such as the re-establishment of trust after a weapons of mass destruction terrorist incident rarely receive significant attention. These limitations could seriously weaken efforts to address the consequences of a chemical, biological, radiological, or nuclear terrorist attack. There is an urgent need, therefore, to re-think current approaches and to develop a broader conception of consequence management. PMID- 11778420 TI - Psychological effects of nuclear and radiological warfare. AB - Not since 1945 has the world experienced nuclear warfare, although there has been the threat of nuclear terrorism and a large number of nuclear/radiological accidents. Most people fear a nuclear/radiological threat even more than a conventional explosion due both to their inability to perceive the presence of radiation with the ordinary human senses and to concerns about perceived long lasting radiation effects. Studies of radiological accidents have found that for every actually contaminated casualty, there may be as many as 500 people who are concerned, eager to be screened for contamination, sometimes panicked, and showing psychosomatic reactions mimicking actual radiation effects. Data from the Hiroshima and Nagasaki attacks revealed widespread acute reactions such as psychic numbing, severe anxiety, and disorganized behavior, and there were later chronic effects such as survivor guilt and psychosomatic reactions. Such responses would likely be common in any future nuclear/radiological accident, terrorist attack, or warfare. PMID- 11778421 TI - Meeting psychological needs after Chernobyl: the Red Cross experience. AB - The explosion that took place in reactor number 4 of the Chernobyl Nuclear Power Plant on April 26, 1986 triggered the worst civilian nuclear disaster ever reported. Following requests for assistance by the Red Cross National Societies of Belarus, Ukraine, and Russia, the International Federation of Red Cross Societies set up the Chernobyl Humanitarian Assistance and Rehabilitation Program in 1990. Although the initial needs assessment mission mentioned psychological needs as an area of interest, it was not until 1997 that the first Psycho-Social Support pilot project started in Belarus. Objectives and strategy for the psycho social support program are detailed, as well as the challenges currently faced by the program. The specific role of the media is also reviewed. Finally, the lessons learned from this experience are reviewed, and suggestions are made for future disaster planning. PMID- 11778422 TI - Psychological casualties resulting from chemical and biological weapons. AB - This symposium addresses the complications encountered by medical planners when confronted by the use or threat of the use of weapons of mass destruction. The types of chemical warfare agents (CWA), their principal target organs, and physiological effects are discussed. We have reviewed the use of CWA in 20th century warfare and otherwise with emphasis on five cases: (1) use of sulfur mustard during World War I; (2) use by Italy against Ethiopia; (3) use in the Sino-Japanese War; (4) relatively well-studied use in the Iran-Iraq conflict; and (5) the use of sarin in the Tokyo subway terrorist incident. We reviewed the additional physiological and psychological consequences of their use and threat of use. Results from training and simulation are discussed. Finally, we present our conclusions derived from the analysis of these historical situations. PMID- 11778423 TI - Psycho-physiological effects of the terrorist sarin attack on the Tokyo subway system. AB - The investigation describes the follow-up of the victims of the 1995 Tokyo sarin attack who were followed by a team at the St. Luke's International Hospital. A symptom questionnaire ("St. Luke's Questionnaire") was developed and given 2, 3, and 5 years following the sarin attack. Somatic and psychological symptoms have continued for 5 years after the incident. New post-traumatic stress disorder diagnostic criteria, which include physical symptoms, were developed and applied for assessment of the outcomes. The St. Luke's cohort was also compared with other Japanese sarin attack cohorts. Interventions, including counseling, medical treatments, and support group activities, were associated with fewer symptoms among the victims. PMID- 11778424 TI - Psychological effects of biological warfare. AB - We compare and contrast psychological and behavioral reactions to bioterrorism with responses to the use of traditional and chemical weapons by terrorists. We discuss the characteristics of biological agents that make them potent agents of terror. We suggest strategies for preparation and response to bioterrorism. We reviewed the literature on psychological, behavioral, and social responses to terrorism, natural disasters, and infectious disease outbreaks. The first psychiatric intervention is to ensure good medical care for illness. Initial psychosocial interventions also include effective and accurate risk communication, management of misattribution of somatic symptoms, and the creation of a recovery environment that restores effective social roles and returns people to their usual sources of social support. Bioterrorism presents special challenges for our society. Domestic bioterrorism preparedness and response plans should reflect realistic consideration of psychological, behavioral, and societal reactions to this novel weapon. PMID- 11778425 TI - Psychosocial effects of the 1994 plague outbreak in Surat, India. AB - The plague outbreak in Surat, India in September 1994 stirred a nationwide panic and a near international isolation of India. These are aspects that need serious attention. A large amount of damage to India's image and an immense economic loss occurred. Some advice for the future is suggested. PMID- 11778426 TI - Prevalence of psychological, somatic, and conduct casualties in war. AB - Combat stress reactions (CSR) have been a common occurrence in the wars of this century. This article reviews data and research on CSR and summarizes the different factors, which correlate with the frequency and the type of CSRs seen. Suggestions for planning for weapons of mass destruction events that are made based on the projected similarities between CSRs seen during combat and those that might be expected following a weapons of mass destruction event. PMID- 11778427 TI - Exercises involving an act of biological or chemical terrorism: what are the psychological consequences? PMID- 11778428 TI - The psychosocial aspect of the Anthrax vaccine: "the Dover experience". PMID- 11778429 TI - The Department of Defense chemical and biological defense program: where we are going. AB - This article provides an overview of the Department of Defense (DoD) Chemical and Biological Defense Program (CBDP). This article highlights the mission and objectives of the DoD CBDP, the general capabilities of systems and technologies being developed or employed to defend U.S. forces against the threat of chemical and biological warfare agents, and improvements made in defensive systems in the years since Operation Desert Storm. PMID- 11778430 TI - Psychological and performance effects of chemical-biological protective clothing and equipment. AB - Civilian emergency response personnel who assist at chemical or biological disaster scenes are likely to be novices at functioning in chemical-biological (C B) protective clothing (CBC) meant for use on contaminated battlefields. Such teams must be aware that CBC imposes numerous physiological, psychophysiological, and biomechanical effects on performance, and significant declines in individual and group performance effectiveness can be anticipated. Cumbersome protective suits, gas masks, rubber gloves, and protective overboots worn to clean up chemical spills or to respond to terrorist use of weapons of mass disruption, produce performance slow-downs requiring up to 30% more time to accomplish tasks, compromise communications, and raise the risk of dehydration, heat injuries, and other environmental and psychological stresses that impinge upon task completion. First-response workers who will wear cumbersome CBC need realistic, confidence building, mission-related training in the C-B uniforms, clothing, and equipment available to them. PMID- 11778431 TI - Collective behaviors: mass panic and outbreaks of multiple unexplained symptoms. AB - The general public, the mass media, and many government officials believe that the use of weapons of mass destruction (WMD) will inevitably lead to mass panic and/or mass hysteria. However, studies of disasters and wars show that disorganized flight in the presence of a real or perceived danger (i.e., mass panic) is rare. On the other hand, in a real or perceived WMD scenario, outbreaks of multiple unexplained symptoms (i.e., mass psychogenic illness, mass sociogenic illness, mass hysteria, or epidemic hysteria) may be prevalent. Many of the symptoms (fatigue, nausea, vomiting, headache, dizziness/lightheadedness, and anorexia) are common in combat and after toxic chemical exposure, chemical weapon exposure, prodromal infectious illness, and acute radiation sickness. PMID- 11778432 TI - Outbreaks of medically unexplained physical symptoms after military action, terrorist threat, or technological disaster. AB - Medically unexplained physical symptoms (MUPS) may present a challenge to clinicians, disaster response organizations, and scientists after future military actions, terrorist threats, or technological disasters. Polarized public discussion over science, policy, and media evidence following such incidents may reinforce the notion of cover-ups, create mutual doctor-patient mistrust, amplify symptom-related psychosocial distress and disability, and lead to unnecessary use of services. Under these circumstances, the clinician must always show respect, empathy, and validation for a patient's concerns. A skeptical attitude may induce efforts by patients to "prove" their symptoms are "real." If MUPS are discounted as a "non-problem," they may become a much bigger public health problem when patients feel their symptoms and concerns have been discounted by unfeeling government clinicians, and patient "horror stories" become grist for media and political mills. PMID- 11778433 TI - The impact of the Oklahoma City bombing on children in the community. AB - This study examined the influence of exposure on post-traumatic stress symptomatology in children following the 1995 Oklahoma City bombing. Over 2,000 children were surveyed 7 weeks after the bombing. Initial reaction and emotional exposure were important predictors of post-traumatic stress symptomatology in the full sample. Children who reported no physical or emotional exposure had significantly lower scores than exposed children on television viewing, initial reaction, and post-traumatic stress symptomatology. Within the nonexposed group, those with high television exposure had significantly more post-traumatic stress symptoms. Children with strong initial reactions should be followed over time, and disaster-related television viewing should be carefully monitored. PMID- 11778434 TI - The course of post-traumatic stress disorder after the Oklahoma City bombing. AB - Oklahoma City bombing survivors (N = 182) were studied 6 months post-bombing and reassessed approximately 1 year later (N = 141) to determine the longitudinal course of post-traumatic stress disorder (PTSD) and other psychiatric disorders. The Diagnostic Interview Schedule assessed lifetime, current, predisaster, and post-bombing psychiatric diagnoses at both assessment points. One-third of the Oklahoma City bombing survivors had PTSD at index, and similar rates were diagnosed at follow-up. More recovery from depression was apparent than from PTSD. No delayed onset PTSD was observed, and all PTSD was chronic. Avoidance and numbing symptoms were dominant in defining the development of PTSD. Early onset and chronicity of PTSD indicate need for prompt and long-term intervention after disasters. Focus on avoidance and numbing symptoms may aid in identification of individuals needing intervention and monitoring the course of PTSD. PMID- 11778435 TI - Evaluation of post-traumatic stress disorders. AB - This paper introduces important considerations in the evaluation of psychological reactions to traumatic events. Proper assessment should include consideration of psychometric, cultural, and ethical issues. Mental disorders frequently observed in the aftermath of trauma (acute stress disorder and post-traumatic stress disorder) and stress (adjustment disorders) are defined, and the reader is provided with information on both general and specific resources for their evaluation. PMID- 11778436 TI - Understanding the chaplain's role in an age of weapons of mass destruction. AB - The possibility and/or use of weapons of mass destruction (WMD), in the same manner as disasters, terrorism, and other large-scale events, will trigger a huge response from the military services, government organizations, and community groups. Deploying a systematic, coordinated, and timely response is the challenge of all crisis response management teams. Victims and rescuers will have different issues and need different types of support at different times before, during, and after such a threat. Spiritual reactions of survivors as a result of WMD will impact diagnosis and treatment of psychological casualties. The chaplain, as the team pastoral care provider, contributes to the design and implementation of an effective, multi-disciplinary, and cohesive intervention strategy to meet today's realization of WMD threat. PMID- 11778437 TI - Dual-edged sword: dealing with the media before, during, and after a weapon of mass destruction event. PMID- 11778438 TI - Pertinent psychological issues in the immediate management of a weapons of mass destruction event. AB - Decisions made and actions taken by crisis and consequence managers during the initial stages of a domestic terrorist incident that involves a weapon of mass destruction will influence the ultimate psychological toll of the disaster. Exploring, in advance, the feasibility of quarantine, participating in training exercises that force decision makers to confront the consequences of their decisions on the behaviors of a population at risk from a weapon of mass destruction agent release, and critically examining the capabilities of mental health crisis intervention teams that might respond to a terrorist event are 3 of 12 suggestions offered to crisis and consequence managers to help them prepare for their roles. PMID- 11778439 TI - Medical aspects of ionizing radiation weapons. AB - The probability of nuclear war is deemed small. A large-scale release of radionuclides into a populated area is considered much more likely. Treatment of radiological casualties is possible even after a detonation that immediately overwhelms surviving local resources. Care would be required at medical centers throughout the country. For those radiological casualties where treatment is most likely to make the difference between survival and death, a window of several days exists in which patients can be identified, dispersed, and therapy initiated. Most deaths due to radiation occur as a result of bone marrow damage and secondary infection. Treatment is based on stimulation of the surviving bone marrow stem cells and protection from infection. With aggressive treatment of immunosuppression, very few deaths should be anticipated at radiation doses of less than 5 Gy. Only those patients who exhibit signs of neurological damage should be considered expectant. All other casualties are candidates for therapy. PMID- 11778440 TI - Calm under pressure and fear under fire: personal experience of a medical officer. AB - Mass casualties during war, civil unrest, or natural disasters can generate chaos and disarray in the emergency room setting. The influx of numerous casualties in a short period of time can paralyze the medical facility and cause irreparable damage to the injured. Maintaining calm and order is very essential for triage of patients, for providing efficient and expeditious medical care, and can save many lives. Coping with fear under fire is one of the most acute problems a medical officer has to face in the battlefield. Not only does he/she have to counsel fellow soldiers, but also he/she has to deal with his/her own anxiety and fear. The following two personal experiences can serve as an instructive example of the kind of problems a medical officer has to face during war. PMID- 11778441 TI - Nuclear, biological, and chemical training in the U.S. Army Reserves: mitigating psychological consequences of weapons of mass destruction. AB - Weapons of mass destruction (WMD) and their associated delivery systems pose a major threat to the national security of the United States. The Department of Defense is pursuing a number of activities to counter paramilitary and terrorist threats from nuclear, biological, and chemical (NBC) agents. These efforts include supporting, training, and equipping the U.S. Army Reserves (USAR) for the medical management of physical injuries and psychological trauma resulting from the use of NBC weapons both in the United States and overseas. The USAR will play an important role in responding to a WMD incident because most of the Army's support assets are in the USAR. The USAR is training to perform its mission in an NBC-contaminated environment by engaging in realistic WMD exercises using state of-the-art protective equipment and medical support. Realistic training builds confidence in medical defenses and in NBC protective equipment. This translates into accomplishing the mission while minimizing the psychological and physical casualties in an NBC-contaminated battlefield or in support of a WMD terrorist incident. PMID- 11778442 TI - Are the psychosocial aspects of weapons of mass destruction incidents addressed in the Federal Response Plan: summary of an expert panel. AB - Within the domestic preparedness community, there is a growing recognition of the importance of psychosocial issues in weapons of mass destruction (WMD) incidents. Whereas social and behavioral issues were only infrequently considered just a few years ago, they are now coming to be seen as central to consequence management efforts. As a result, discussions in the domestic preparedness community are beginning to consider the extent to which psychosocial effects are addressed in the Federal Response Plan and the degree to which additional preparedness and response steps may be needed. To grapple with this crucial issue, an expert panel was brought together at the International Conference on the Operational Impact of Psychological Casualties from Weapons of Mass Destruction. The panel brought together a wide range of specialists from federal agencies, the armed services, and the academic community. This article summarizes the views and assessments of the panelists as well as their policy recommendations for enhancing preparedness. PMID- 11778444 TI - Performance decrement after combined exposure to ionizing radiation and Shigella sonnei. AB - Ionizing radiation could increase morbidity from common bacterial infections in military personnel on the modern battlefield. The combined effects of a sublethal dose of ionizing radiation and the bacterial diarrheal agent Shigella sonnei on body weight and forelimb grip strength in mice were assessed over a 30-day period. Individually housed B6D2F1 female mice were divided into four groups: control, sham irradiation + gavage with saline vehicle; 3 Gy 60Co gamma radiation at 0.4 Gy/min radiation + saline gavage; sham irradiation + 1.3 x 10(8) colony forming units (CFUs) S. sonnei via gavage, administered 4 days postirradiation; and the combination of 3 Gy 60Co gamma radiation + 1.3 x 10(8) CFUs S. sonnei. Behavioral tests were conducted 3 days preirradiation and on days 9, 14, and 22 postirradiation. Body weight was significantly reduced in the radiation + Shigella group on days 5 to 10 postirradiation. Forelimb grip strength was reduced for mice in the radiation + Shigella group on days 9 and 14 postirradiation. These data demonstrate that an exposure to gamma radiation in combination with the bacterial agent S. sonnei can lead to a synergistic loss of body weight and degradation in performance. PMID- 11778443 TI - Detection of depleted uranium in biological samples from Gulf War veterans. AB - During the Persian Gulf War, soldiers may have inhaled, ingested, and/or experienced wound contamination by depleted uranium (DU), which is used in military projectiles and armor. DU is produced by depleting natural uranium of 234U and 235U during the uranium-enrichment process. Although the long-term effects of significant DU exposures require investigation, many veterans express fears about its impact on health. An assay by which DU exposure can be assessed would not only be a useful research tool, but the information could help mitigate the concerns of exposed individuals. In this study, urine samples from individuals enrolled in the Depleted Uranium Follow-Up Program at the Baltimore Veterans Administration Medical Center were examined for uranium content. Isotopic composition of urine uranium was determined by measuring the 235U/238U ratio, using an inductively coupled plasma mass spectrometer. Using this method, natural and depleted uranium could be readily differentiated. By demonstrating the absence of DU in soldiers who suspect exposure by inhalation or ingestion, the assay should reduce psychological stress in these individuals. PMID- 11778445 TI - An animal model for studying therapeutic drugs against post-traumatic stress disorder. AB - An animal model for the evolvement of post-traumatic stress disorder (PTSD) was developed by simulating the hormonal consequences of prolonged stress via the continuous administration of corticosterone by subcutaneously implanted sustained release pellets. Behavioral, morphological, and biochemical effects were recorded and analyzed. This model has shown cognitive deficits as well as hippocampal damage in the rat similar to those found in PTSD patients. The model was also used to test a therapeutic treatment against stress-induced brain damages. Concomitant treatment with the L-type calcium channel blocker, nimodipine, protected young rats from corticosterone-induced morphological brain changes but not cognitive impairments. The proposed animal model may be useful for testing the efficacy of various neuroprotective drugs. Development of an effective drug treatment for use after a traumatic event and through the trauma period might prevent permanent brain damage and the development of PTSD. PMID- 11778446 TI - Willingness to pay for defense against weapons of mass destruction. AB - A survey assessed the willingness to pay for defense against weapons of mass destruction. The results were evaluated according to the benefit to society. The results indicated preferences for increased spending on intelligence gathering, training, and equipment. We concluded that the United States is spending less for weapons of mass destruction defense than the sample population was willing to pay. PMID- 11778448 TI - Psychological problems associated with mission-oriented protective gear. AB - "Gas mask phobia," a form of claustrophobia, impacts the ability of many service members to perform their mission. Historically, some soldiers have not donned, or quickly removed, their personal protective respirators because of discomfort, ignorance, or shame. Traditionally, little attention has been paid to this as a readiness issue. Exact numbers of service members who are unable to tolerate their masks are unknown. This phobia can be avoided with adequate training and treated with principles of desensitization, but more research is needed in early identification and treatment. PMID- 11778447 TI - Fear of radiation in U.S. military medical personnel. AB - The fear of radiation, even low-level radiation, could significantly impair military operations. To measure knowledge of and attitudes toward radiation, the Armed Forces Radiobiology Research Institute developed a questionnaire that military medical personnel completed both before and after the 3-day Medical Effects of Ionizing Radiation (MEIR) course. Findings included a positive correlation between the resulting increased knowledge and more positive attitudes. No gender effects were observed for knowledge or attitude, but both education level and military rank were related to knowledge and attitude. PMID- 11778449 TI - Biodosimety Assessment Tool: a post-exposure software application for management of radiation accidents. AB - The Biodosimetry Assessment Tool software application under development will equip health care providers with diagnostic information (clinical signs and symptoms, physical dosimetry, etc.) germane to the management of human radiation casualties. Designed primarily for prompt use after a radiation incident, the user-friendly program facilitates collection, integration, and archiving of data obtained from exposed persons. Data collected in templates are compared with established radiation dose responses obtained from the literature to provide multiparameter dose assessments. The program archives clinical information (e.g., extent of contamination, wounds, infection, etc.) useful for casualty management, displays relevant diagnostic information in a concise format, and can be used to manage both military and civilian radiation accidents. In addition, monitoring of diagnostic information of individuals using this program could potentially minimize the severity of psychological casualties by making a marked impact on the way that both radiation casualties and the worried well view their exposure, dose, and future risk for the development of disease. PMID- 11778450 TI - Combined effects of Venezuelan equine encephalitis IIIA virus and gamma irradiation in mice. AB - The combined effects of injury from exposure to ionizing radiation and the potential biological warfare agent Venezuelan equine encephalitis (VEE) virus remain largely unknown. To study these effects, 4- to 5-week-old B6D2F1/J female mice were given a sublethal whole-body 7 Gy dose of 60Co gamma-photon radiation followed 48 hours later by aerosol or intraperitoneal challenge with enzootic VEE IIIA virus. Survival was observed for 30 days. A single sublethal 7 Gy dose of gamma radiation reduced the LD50/30 of VEE IIIA virus, in intraperitoneal challenged mice by a factor of 10(4) from 1.1 x 10(6) plaque-forming units (pfu) to 1 x 10(2) pfu, and in aerosol challenged mice, by a factor of 5 from 70 pfu to 14 pfu. These findings further confirm there is a combined effect of exposure to ionizing radiation and biological warfare agents, which could be devastating to unprotected populations and thus should be investigated further. PMID- 11778451 TI - Chemical warfare agents: a primer. PMID- 11778452 TI - Wake-up call: a bioterrorism exercise. AB - Operation Wake-Up Call was a simulated bioterrorism exercise conducted in Waukesha County, Wisconsin (Metropolitan Milwaukee) on November 6, 1999. The purpose of the exercise was to test and evaluate the emergency response capability of local municipal, county, state, federal, and reserve military agencies to a weapons of mass destruction terrorist act. The exercise simulated a biological agent (Bacillus anthracis spores) release, a hostage-taking event, and the management of multiple biological and conventional weapons casualties that overwhelmed local first responders' capability. The exercise involved local, county, state, and federal agencies in a joint operational environment featuring integrated command and control systems. This report describes the primary purpose, goals, and assumptions of the exercise and reports on the evaluation of Wake-Up Call by the participating agencies. PMID- 11778453 TI - [Na+/H+ exchange inhibitors for ischemic diseases]. AB - Cariporide, HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na(+)-H+ exchange (NHE) subtype 1 inhibitor, has cardioprotective effects including an antifibrillatory effect on the coronary ischemia/reperfusion induced arrhythmias not only in in vitro, but also in vivo animal hearts, which might be induced by intracellular Ca2+ overload following myocardial ischemia. This antifibrillatory effects on reperfusion arrhythmias were observed even when the drug was administered after induction of coronary ischemia or even when the drug was administered simultaneously with reperfusion. Other NHE inhibitors also have similar antiarrhythmic and antifibrillatory effects as cariporide and these drugs had almost no deleterious effects on the heart rate and blood pressure, nor ECG parameters. The antifibrillatory mechanism of NHE inhibitors may be due to their NHE inhibition as judged by the doses used, and they may become useful for treating or preventing arrhythmias in patients with coronary artery diseases. PMID- 11778454 TI - [Perspectives on tetrahydrobiopterin research]. AB - Tetrahydrobiopterin ((6R)-L-erythro-tetrahydrobiopterin, BH4) is de novo synthesized from GTP. Enzymes involved in its synthesis are the rate limiting enzyme GTP cyclohydrolase I, 6-pyruvoyl tetrahydropterin synthase (PTPS) and sepiapterin reductase. Abnormalities in the metabolism of BH4 have been demonstrated in some diseases affecting the central nervous systems such as atypical phenylketonuria, hereditary progressive dystonia (Segawa's disease). Furthermore, BH4 has been shown to be involved in vascular protection. It is suggested that the dysfunction of endothelial BH4 leads to atherosclerosis. Recently we established BH4-deficient mice by disrupting the PTPS gene to investigate the effects of BH4 depletion on the animals and the involvement of BH4 in regulating biological functions including neural systems. Investigation utilizing this model animal can contribute to the development of new therapeutic strategies toward various diseases involving neurological and vascular systems. Pterin derivatives other than biopterin may also be involved in the regulation of a variety of biological functions. We found that ciliated protozoan Tetrahymena pyriformis synthesizes tetrahydromonapterin, isomer of BH4, and its levels alter according to the progress of the cell cycle. How pterin derivatives are related to the human physiology and diseases is an interesting subject of investigation. PMID- 11778455 TI - [In vivo microdialysis technique on rat myocardium]. AB - The microdialysis procedure is a technique that has been established for some years. The heart, however, has several difficulties in the application of this technique. The heart is the beating in vivo, in contrast to other organs. I developed the flexibly mounted microdialysis technique, which involves the synchronized movement of the tip of the probe with the beating heart to reduce tissue injury. With this technique, it is feasible to make stable and long-term measurements of interstitial biological substances. By employing the flexibly mounted microdialysis technique, I will demonstrate that the monitoring of free radical generation and the level of adenosine measured during AMP perfusion that gives an index of the activity of ecto-5'-nucleotidase in the tissue. In the future, this technique will have versatile applications for useful studies to elucidate the actual mechanism in the pathogenesis of heart disorders. PMID- 11778456 TI - [Establishment of the method for the measurement of sphingosine-1-phosphate in biological samples and its application for S1P research]. AB - Sphingosine 1-phosphate (S1P), one of the sphingolipid metabolites, has been shown to participate in a variety of cellular responses including proliferation, differentiation, adhesion, motility, and apoptosis. These cellular responses elicited by S1P were first thought to be mediated through an intracellular target(s), but extracellular mechanisms through G-protein-coupled S1P receptors have also been suggested. In addition to the studies examining the functions of the lipid on the cells and tissues, the measurement of the lipid concentration is also important for understanding the physiological and pathophysiological roles of the lipid. We have recently developed a novel quantitative method for measurement of S1P, which was based on the competition of S1P in the samples with the labeled S1P on the S1P receptor Edg-1. Here, we compared our method with previously published ones in several points including specificity and simplicity. We further presented our recent results obtained by using this novel quantitative method and finally mentioned the prospects of the S1P measurement in lipid research, especially in relation to several disorders. PMID- 11778457 TI - [Lipid-lowering drugs]. AB - Accumulating evidences in recent major clinical studies have shown the importance of anti-hyperlipidemic treatment in preventing atherosclerotic cardiovascular diseases. Lipid-lowering drugs can be divided into HMG-CoA reductase inhibitors (statins), bile-acid sequestrants (resins), nicotinic acid, fibrates and probucol. Among them, statins had revolutionary impact on the treatment of hyperlipidemia since pravastatin, which was developed in Japan, was launched in 1989. Several lipid-lowering drugs are now under development in Japan, including pitavastatin, rosuvastatin, F-1394 (ACAT inhibitor), CS-505 (ACAT inhibitor) and NO-1886 (LPL activator). In this review, characteristics of these new lipid lowering drugs will be discussed. PMID- 11778458 TI - [Ramatroban (Baynas): a review of its pharmacological and clinical profile]. AB - Bayer has been interested in the observations that metabolites of arachidonic acid are involved in allergy and inflammation. Ramatroban was thus developed as a therapeutic agent for allergic and inflammatory diseases. Ramatroban showed an antagonistic action on the thromboxane A2 (TXA2) receptor in in vitro experiments using platelets or arteries. It inhibited the permeability of capillary and also the infiltration of eosinophils in nasal mucosa. Ramatroban had an inhibitory effect on the nasal resistance stimulated by either U-46619 or antigen challenge in in vivo experiments. The concentration of nasal TXA2 was increased when the antigen was challenged to allergic patients. Clinical trials demonstrated that ramatroban decreased sneezing, rhinorrhea, and rhinostenosis in patients enrolled in the study. No serious adverse reaction of ramatroban was observed in patients throughout the trials. The treatment with ramatroban is safe and improves nasal symptoms. PMID- 11778459 TI - [Effects of fluvoxamine on both the desired anxiolytic effect and the adverse motor incoordination and amnesia induced by benzodiazepines]. AB - Fluvoxamine, a selective serotonin reuptake inhibitor, is frequently used along with benzodiazepine anxiolytics in clinics. In this study, the effects of fluvoxamine on the anxiolytic effects as well as adverse effects of benzodiazepines were examined in the light/dark box, rota-rod and passive avoidance tests using mice. Diazepam, ethyl loflazepate and its active metabolite, CM7116, were used as benzodiazepine anxiolytics. The anxiolytic effects of diazepam, ethyl loflazepate and CM7116 were potentiated by intraperitoneal treatment with fluvoxamine at 10 mg/kg, whereas only those of ethyl loflazepate were potentiated by fluvoxamine at 45 mg/kg. The motor incoordination and amnesia induced by ethyl loflazepate and CM7116 were not affected by fluvoxamine, although these adverse effects of diazepam were potentiated by fluvoxamine at 45 mg/kg. Fluvoxamine itself showed no effects in any of the tests. These results suggest that low-dose fluvoxamine potentiates the anxiolytic effects of benzodiazepines, while high-dose fluvoxamine augments the adverse effects depending on the benzodiazepine used. Consequently, when fluvoxamine is administered along with benzodiazepines, the doses of both fluvoxamine and benzodiazepines should be carefully chosen to achieve anxiolytic effects without any adverse results. PMID- 11778460 TI - Amniotomy. Necessary intervention or bad habit? PMID- 11778461 TI - Our environment, our health. PMID- 11778462 TI - Tracking & treating anthrax. Biological terrorism resources for health care providers. PMID- 11778463 TI - Why women quit using Depo-Provera? PMID- 11778464 TI - Thinking strategically about women's health. PMID- 11778465 TI - Dysfunctional defecation. "Why 'Jane' can't poop!". PMID- 11778466 TI - Nursing's future under fire. How nursing associations, legislators are addressing the shortage. PMID- 11778467 TI - Sending baby home safely. Developing an infant car seat testing program. PMID- 11778468 TI - Nursing at a crossroads. Exploring the need for advanced nursing education. PMID- 11778469 TI - Cardiovascular guidelines for women released. PMID- 11778470 TI - Estrogen or no Estrogen. A Hormone Therapy Dilemma. . PMID- 11778471 TI - [Pay attention to gerontal tuberculosis]. PMID- 11778472 TI - [The studies on the molecular mechanism of rifampin-resistant Mycobacterium tuberculosis]. AB - OBJECTIVE: To evaluate the molecular mechanism of rifampin (RFP)-resistance of M. tuberculosis, and to provide evidence of molecular genetics for basic and clinical research of tuberculosis. METHODS: rpoB gene mutation of M. tuberculosis was detected with PCR-SSCP from 262 clinical isolates, including 74 drug sensitive strains, and 188 RFP-resistant only or multiple drug-resistant strains of M. tuberculosis, collecting from Henan, Hebei and Anhui province, Beijing and Shanghai cities. Plasmids were extracted from 76 clinical isolates of M. tuberculosis with alkaline bacteriolytic methods. RESULTS: Mean mutation rate of rpoB gene was 92% in the RFP-resistant clinical isolates of M. tuberculosis. Respectively, the mutation rate was 90.0% in Henan province, 94% in Hebei province, 91% in Anhui province, 91% in Beijing city and 92% in Shanghai city. There was no significant difference between results from the provinces and the cities (chi 2 = 0.42, P > 0.05). However, mutation of rpoB gene was not detected in 74 sensitive clinical isolates of M. tuberculosis. Moreover, in 76 clinical isolates of M. tuberculosis the plasmids were not found, including 29 sensitive strains, 33 RFP-resistant only or multiple drug-resistant strains and 14 RFP, isoniazid, streptomycin and ethambutol-resistant clinical isolates. CONCLUSIONS: This study confirmed the strong correlation between the RFP-resistance and the mutation of the rpoB gene, which might be a major molecular mechanism of RFP resistance in M. tuberculosis. No evidence shows that M. tuberculosis has the plasmid, which mediates RFP resistance to M. tuberculosis. PMID- 11778473 TI - [Imaging diagnosis for abdominal tuberculous lymphadenopathy]. AB - OBJECTIVE: To evaluate the value of X-ray imaging for diagnosing abdominal tuberculous lymphadenopathy. METHODS: 27 cases of tuberculous lymphadenopathy proved by clinical or pathohistological evidence were collected, all of which were examined with radiological imaging methods. RESULTS: The typical CT findings enlarged lymph nodes with peripheral or multilocular enhancement. Enlarged lymph nodes with multiple flecked or massive calcifications were important for diagnosis. Ultrasound examination showed enlarged lymph nodes with uniform echo (less than 2 cm) and with heterogeneous echo (larger than 2 cm). The aim of the barium meal examination of the gastrointestinal tract was to find tuberculous lymphadenopathy encroaching on intestine or merged with intestinal tuberculosis. Abdominal X-ray plain film was helpful to find the calcified tuberculous lymphadenopathy and intestinal obstruction. CONCLUSIONS: Various imaging methods have shown their diagnostic value, but CT was the most important tool for definite diagnosis of tuberculous lymphadenopathy. Ultrasound was more useful for follow-up cases. PMID- 11778474 TI - [WHO sample survey on drug resistant tuberculosis in Zhejiang, China]. AB - OBJECTIVES: To obtain the data on initial and acquired drug resistance, and to evaluate the efficacy of ongoing tuberculosis (TB) control strategies. METHODS: According to the Guidelines for Surveillance of Drug Resistance in Tuberculosis of WHO/IUATLD, randomly selected 30 counties with population proportionate cluster sampling method. Proportion method was used for drug sensitivity test, laboratory quality control was done by Korean super-country reference laboratory. RESULTS: 1,013 TB patients were enrolled in 30 counties, 954 were culture positive, and one with non-tuberculous mycobacteria. The culture positive rate was 94.6%, the contaminated rate was 3.2%. Drug susceptibility testing against streptomycin (SM), isoniazid (INH), rifampicin (RFP) and ethambutol (EMB) were performed in 953 cases, the total drug resistant rate was 21.5%, the initial drug resistant rate was 14.8%, the initial multi-drug resistance was 4.4%, the acquired drug and multi-drug resistant rates were 59.0% and 34.7%, respectively. CONCLUSIONS: The initial drug resistant rates were decreasing in comparison to 1990 (24.0%), suggesting good effect of DOTS policy implemented in Zhejiang province. However, multi-drug resistant rate was higher in this province than some other countries, indicating more attention should be paid to this situation. PMID- 11778475 TI - [Bcl-2 antisense oligodeoxyribonucleotide increases apoptosis of lung carcinoma cells induced by cisplatin]. AB - OBJECTIVE: To study the effect of antisense oligodeoxyribonucleotide (ODN) to apoptotic suppress gene bcl-2 on apoptosis of lung carcinoma cells induced by cisplatin. METHODS: The lung carcinoma cells expressing bcl-2 were chosen to participate in this experiment. Cultured cells were divided into 7 groups: ODN, nonsense, ODN + cisplatin, nonsense + cisplatin, cisplatin, lipofectin and control. Bcl-2 antisense or nonsense mixed with lipofectin was added into above corresponding cultured cells. After cultured for 6 hours, cisplatin was added into corresponding groups. The cells were cultured again for 16 hours. And then, the cells were smeared on slides. Apoptotic cells were labeled with TdT-mediated dUTP nick end labeling (TUNEL) method on cell smears. Apoptotic index (AI) was counted to show the percentage of apoptotic cancer cells. The immunocytochemistry was used to detect the expression of bcl-2 in carcinoma cells. RESULTS: The bcl-2 expression of cancer cell in ODN group was significantly decreased compared to the control and nonsense groups. The AI of ODN + cisplatin group was 16.4 +/- 1.7, cisplatin group 4.1 +/- 0.8, antisense group 5.9 +/- 0.2, nonsense group 3.3 +/- 0.7, nonsense + cisplatin 7.6 +/- 1.1, lipofectin 5.1 +/- 0.9, control group 3.6 +/- 0.6. The AI of antisense + cisplatin group was significantly higher than that of other groups. CONCLUSION: Antisense oligodeoxyribonucleotide to bcl-2 can inhibit significantly the expression of bcl-2 of lung cancer cells and increase apoptosis of cancer cells induced by cisplatin. PMID- 11778476 TI - [The variation of nasal obstruction in patients with OSAS]. AB - OBJECTIVE: To study the variation of nasal resistance and its possible relationship to obstructive sleep apnea. METHODS: The detection of nasal resistance and polysomnography were performed in 30 normal subjects, 30 snoring patients and 60 patients with OSAS. RESULTS: The study reveal that nasal resistance of the patients with OSAS (1.06 +/- 4.25) Pa.s/ml, (2.29 +/- 9.74) Pa.s/ml or snoring (0.71 +/- 0.31) Pa.s/ml was higher than that of normal group (0.40 +/- 0.13) Pa.s/ml (P < 0.01). There was a positive correlation between nasal resistance and snoring index (r = 0.258, P < 0.01), but there was no correlation among AHI, waken intervals, and nasal resistance. CONCLUSION: Nasal resistance increased in the patients with snoring or OSAS, it may be a factor related with OSAS. PMID- 11778477 TI - [Laboratory study on protective and therapeutic effects of pinacidil on pulmonary vascular remodeling in rats with hypoxia-induced pulmonary hypertension]. AB - OBJECTIVE: To investigate the protective and therapeutic effects of pinacidil on hypoxia-induced pulmonary hypertension(HPH) and pulmonary vascular remodeling. METHODS: 46 male Wister rats were divided into control group, hypoxic group and treated group (hypoxic rat treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia [(10 +/- 0.5)% O2, 4 weeks)]. The mean pulmonary arterial pressure (mPAP) and right ventricle/left ventricle and septum [RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphmetric analysis under microscopes in three groups. RESULTS: (1) The level of mPAP(28.4 +/- 2.8) mm Hg and RV/(LV + S) (0.30 +/- 0.03) were significantly higher in the hypoxic group than (16.2 +/- 1.8) mm Hg and (0.22 +/- 0.03) in control group respectively (P < 0.01). Morphometry investigation showed that the external diameter became smaller and that ratio of vascular wall thickness to external diameter (MT%) (25.7 +/- 2.6)% and ratio of vascular wall area to total area (MA%) (75.3 +/- 5.6)% significantly increased in the hypoxic group. (2) The mPAP(23.3 +/- 2.6) mm Hg, RV/(LV + S) (0.27 +/- 0.04) and pulmonary vascular pathologic changes MT%(22.1 +/- 2.5)% and MA% (67.0 +/- 6.1)% significantly decreased in the treated group, indicating that pinacidil inhibited HPH and hypoxia-induced thickening and muscularization of small pulmonary arteria. CONCLUSION: Pinacidil may partly prevent the development of HPH and pulmonary vascular remodeling. PMID- 11778478 TI - [Epidemiological survey and analysis on bronchial asthma in Guangdong Province]. AB - OBJECTIVE: To survey asthma prevalence and risk factors of asthma in Guangdong and then to provide a basic consideration for research and preventive and therapeutic poliaes for control of asthma. METHODS: Using uniform scheme, procedures and questionnaire, performing stratified-cluster-disproportional random-sampling survey for the population in six areas: Santou, Shenzhen, Zhanjiang, Shaoguan, Fushan and Guangzhou; quantitative sample the prevalence rate quantitated is 1.5% (P = 0.015, q = 0.985), a sampling number stratified = 178 x 0.985/0.015 = 11,689, if the whole province were stratified into six areas, a total of 70,134 persons were supposed to be investigated, in this survey 71,867 subjects were actually examined; all the original data were inputted into soft discs in the same form of data base structure variable definition table, and then were statistically analyzed with spas 8.0 for windows on P III/450 computer, all the prevalence rates were compared by chi 2 test. RESULTS: In this survey 676 asthmatics were found, the overall prevalence rate was 0.94%, the ratio of male to female was 1.38:1; the rate of adults was 0.99% and that of children was 0.73%, three groups with higher prevalence were children of preschool period (age < 7 years, 1.03%), young period (age 18-25 years, 1.00%) and senile period (age 66-75 years, 2.99%); the rate of city (Fushan, 1.38%) was higher than that of rural area (Zhanjiang, 0.47%); the rate of old district (1.70%) was higher than that of the new district (0.23%) in Guangzhou and the rate of historic city (Fushan, 1.38%) was higher than that of the newly developed city (Shenzhen, 0.64%); risk factors found among 676 asthmatics, persons keeping pets (cat, dog, fowl, bird) in home were reported by 46.0% (311/676), those keeping cat was 43.1% (134/311), particularly those keeping cat and both cat and dog accounted for 61.7% (192/311). Persons often exposed to side-stream smoke were reported by 54.7%. Asthmatics with allergic rhinititis were reported by 38.2%. The attack contributed to change temperature or to inhale cold air was 41.6% respectively. CONCLUSION: This survey had basically reflected the distribution, Frequency and intensity of asthma, the overall prevalence rate was 0.94% from which it would be estimated that there could be 670,000 asthmatics in Guangdong; the relative data will provide basis for research work concerned and mass prevention and treatment of asthma. PMID- 11778479 TI - [Modification of facial mask on the dead space effect in non-invasive mask ventilation]. AB - OBJECTIVE: There were reports concerning the CO2 rebreathing during non-invasive positive pressure ventilation (NIPPV) with full face mask. It is our hypothesis that modification of the mask from one way connection to two ways connection by making a side hole in the mask makes it possible that CO2 inside the mask could be washed out by a constant flow through the mask. METHODS: A randomized self control study on CO2 rebreathing was conducted in 7 COPD patients to compare the modified set-up with the conventional one. A BiPAP-30 ventilator and a plateau exhaustion valve (Respironics USA) were employed in the study. In the modified two ways set-up, the exhaustion valve (with distal end blocked) was connected to the side hole of the mask, so that a constant base flow could pass through the mask to the exhaustion valve. The average base flow was 0.43 LPS. The parameters were set as following: S/T mode, f: 15 BPM, pressure support level: 8 cm H2O. Three different levels of PEEP (2, 3 and 5 cm H2O) were used to investigate the PEEP level on CO2 rebreathing. Flow and CO2% were constantly recorded with computer data acquisition and analysis system (Microcal Origin). RESULTS: In conventional set-up, there was obvious CO2 rebreathing (rebreathing volume: 83.1 +/- 32.9 ml). In modified connection, the rebreathing volume was only (0.1 +/- 0.4) ml (P < 0.001). CONCLUSION: There was obvious CO2 rebreathing during full face mask NIPPV in conventional set-up. A modified two ways connection could reduce CO2 rebreathing to be near zero, which might be important in the management of hypercapnic respiratory failure with NIPPV. PMID- 11778480 TI - [Advanced research on quick culture techniques of mycobacteria]. PMID- 11778481 TI - [Induced sputum to assess airway inflammation]. PMID- 11778482 TI - [Thoughts on guideline for clinical application of fiberoptic broncoscope]. PMID- 11778483 TI - [Elevated substance P content in sputum and plasma in patients with COPD and its relationship with FEV1/FVC]. AB - OBJECTIVE: To investigate the role of substance P(SP) of the nonadrenergic system within airways in the pathogenesis of COPD, and analyze the relationship between level of SP and FEV1/FVC in COPD patients. METHOD: SP concentration in sputum and plasma in 20 patients with COPD and 20 normal volunteers was examined and was measured by radioimmunoassay. RESULTS: The sputum SP concentration was significantly higher in patients with COPD (57.3 +/- 14.5) pmol/L than that in normal volunteers(5.9 +/- 2.6) pmol/L, P < 0.01, the plasma SP concentration was significantly higher in COPD patients (8.6 +/- 3.9) pmol/L than that in normal volunteers (3.8 +/- 2.0) pmol/L, P < 0.05. The plasma and sputum SP concentration correlated with FEV1/FVC in COPD patients (r = -0.591, r = -0.642, P < 0.05). CONCLUSION: These data suggest that neurogenic inflammation may be involved in the airway inflammation process and subsequent airway narrowing in COPD. PMID- 11778484 TI - [The extent of paradoxical thoracoabdominal motion during exercise was improved with oxygen therapy in patients with stable moderate to severe chronic obstructive pulmonary disease]. AB - OBJECTIVE: To assess the synergetic change of thoracoabdominal motion in COPD patients during incremental exercise testing, and to evaluate the effect of oxygen therapy on thoracoabdominal synergetic motion. METHODS: 30 stable moderate to severe COPD patients performed incremental exercise test with ergometer twice while breathing either air or 30% oxygen. Thoracoabdominal motion (assessed by TCD/VT) was monitored with respigraph during the whole test. RESULTS: 18 of 30 patients had TCD/VT > 1.20 during maximal exercise. TCD/VT at maximal exercise (TCD/VTmax) was significantly correlated with FEV1, FVC, MVV and PaCO2(r = -0.66, -0.63, -0.51, and 0.51), but not correlated with DLCO. The thoracoabdominal synergetic motion could be obviously improved with oxygen therapy. CONCLUSIONS: The change of thoracoabdominal synergetic motion during exercise in COPD patients was related with ventilatory function and blood gases. Oxygen therapy could obviously ameliorate paradoxical thoracoabdominal motion. PMID- 11778485 TI - [A study of influence of zafirlukast to anoxic pulmonary hypertension in rats]. AB - OBJECTIVE: To investigate possible mechanism of the influence of zafirlukast to anoxic pulmonary hypertension in rats. METHODS: Forty wistar rats were divided into four groups in random: (1) control group; (2) anoxic pulmonary hypertension group; (3) zafirlukast preventive group; (4) zafirlukast therapeutic group. Pulmonary arterial pressure was measured, naemo kinitic indexes were recorded. RESULTS: In the anoxic group and control group, the difference of mPAP was remarkable, P < 0.01. When zafirlukast preventive group and the therapeutic group compared with the control group, there was no statistical difference, P > 0.05. When the preventive group and the therapeutic group compared with the hypoxia group, P < 0.01. In the hypoxia group, the content of NO in the plasma, broncho alveolar lavage solution, and the lung tissue showed remarkable significance compared with that of control group, P < 0.01. The content of NO2-./NO3-. in the preventive group showed remarkable significance compared with hypoxia group, P < 0.05, P < 0.01. The content of NO2-./NO3-. in the therapeutic group showed remarkable significance compared with hypoxia group, P < 0.01. The content of collagen in hypoxia group was remarkable highened compared with that of control group, P < 0.01. The content of collagen in preventive group and therapeutic group showed remarkable significance compared with hypoxia group, P < 0.01, P < 0.05. CONCLUSIONS: The results indicate that zafirlukast can lower anoxic pulmonary hypertension, one of its mechanisms may be related with its depressing the sediment of collagen on lung tissue, adjusting NO level in rats and anti damaging effect of free radicals. PMID- 11778486 TI - [The study of T helper cell subsets and relationship to relative cytokines and ventilatory function in asthmatic patients]. AB - OBJECTIVE: To investigate the changes of T helper cell(TH) subsets and relationship to the relative cytokines, serum total IgE, eosinophil count and ventilatory function in asthmatic patients. METHODS: 20 asthmatic patients and 10 healthy subjects were selected. The counts of the TH subsets, the level of IL-4 and IFN-gamma in the supernatant of peripheral blood mononuclear cell(PBMC), serum total IgE concentration and eosinophil count in peripheral blood were determined in acute attack and stable patients with asthma and healthy subjects. RESULTS: The TH2/TH1 ratio in the acute attack and the stable patients with asthma were increased significantly, compared with that in normal group (P < 0.01). The relation analysis showed that the value of TH1 had significantly positive relation with that of IFN-gamma, the value of TH2 had significantly positive relation with that of IL-4. The total serum IgE had significantly positive relation with the level of IL-4. FEV1 had significantly positive relation with that of TH1, negative relation with that of TH2, and TH2/TH1 significantly. The total serum IgE and the number of eosinophils had significantly positive relation with that of TH2. CONCLUSION: The balance of TH in asthmatic patients deviates significantly. The deviation of balance of TH has relation with severity of asthma. PMID- 11778487 TI - [Applications of aryl hydrocarbon hydroxylase in diagnosis of lung cancer]. AB - OBJECTIVE: To develop a new biomarker and improve early diagnosis of lung cancer in clinic. METHODS: Aryl hydrocarbon hydroxylase (AHH) activity in peripheral lymphocytes was detected using spectrofluorometer in 51 healthy subjects, 30 patients with benign lung diseases, 93 patients with lung cancer (including 30 patients with lung adenocarcinoma, 30 with lung squamous carcinoma, 33 with small cell lung cancer, 28 of them were at I, II stage, 35 at III stage, 30 at IV stage), and the results were compared with carcinoembryonic antigen(CEA). RESULTS: AHH activity in peripheral lymphocytes was (4.9 +/- 2.1) pmol.min-1 x 10(-6) cells in patients with lung cancer, (7.3 +/- 1.9) pmol.min-1 x 10(-6) cells in patients with lung squamous carcinoma, (1.1 +/- 0.7) and (1.2 +/- 0.6) pmol.min-1 x 10(-6) cells in healthy subjects and patients with benign lung diseases respectively. It is indicated that AHH activity in peripheral lymphocytes was significantly increased in patients with lung cancer, especially with lung squamous cancer. Of patients with lung cancer, AHH activity was (3.7 +/ 1.4) pmol.min-1 x 10(-6) cells in patient at stage I, II, (5.1 +/- 2.1), (7.1 +/ 1.8) pmol.min-1 x 10(-6) cells at stage III and stage IV, and AHH activity increased when patients deteriorated, vice versa. Diagnosis evaluation test indicated that AHH was over 80% in both sensitivity and specificity. AHH relative risk to lung cancer was 2.83. CONCLUSIONS: AHH is a promising marker of lung cancer which is special for lung squamous carcinoma, it can be used in clinical diagnosis, mornitoring and prognosis estimating in patients with lung cancer. PMID- 11778488 TI - [Clinical analysis of 5 cases of relapsing polychondritis]. AB - OBJECTIVE: To describe the clinical manifestation of relapsing polychondritis(RP) and evaluate the medical therapy of RP, especially management of airway stenosis with intervening method. METHOD: Retrospective analysis of 5 cases of RP treated in our hospital since 1995 with reviewing of large series of cases in reported literatures. RESULT: RP is a rare multisystem disorder characterized by recurrent inflammation and progressive degeneration of cartilaginous structure and connective tissue. Medical treatment with corticosteroids, immunosuppressive drugs and dapsone could not interrupt the progression of the disease. Involvement of the respiratory tract is life-threatening and intervening therapy such as tracheostomy, endotracheal intubation or tracheobronchial stents is needed, one case of relieving severe dyspnea caused by extensive tracheobronchial collapse in RP with self-expanding metallic stents was presented. CONCLUSION: It is important to make the diagnosis of RP according to the clinical features and carry out medial treatment at early stage, positive airway pressure support and intervening methods to prevent the airway collapse should be considered when the laryngotracheobronchial involvement aggreviates. PMID- 11778489 TI - [The significance of detecting tumor necrosis factor-alpha and its receptors in serum and pleural effusion in differentiating tuberculosis and malignant pleural effusions]. AB - OBJECTIVE: To investigate the significance of TNF-alpha and its soluble receptors (sTNFR-I and sTNFR-II) in differentiating benign and malignant pleural disease. METHODS: TNF-alpha and its soluble receptors (sTNFR-I and sTNFR-II) were detected using ELISA method in the serum and pleural effusion of 25 cases of tuberculosis pleural effusion and 28 cases of malignant pleural effusion, and in the serum of 32 cases of normal control. RESULTS: TNF-alpha level in the serum of tuberculosis patients with pleural effusion is (16.4 +/- 6.2) ng/L, lower than that in the serum of malignant pleural effusion patients (20.5 +/- 10.9) ng/L (P < 0.01), but higher than that in the serum of normal control (11.0 +/- 2.9) ng/L (P < 0.01). TNF-alpha level in the pleural effusion of tuberculosis patients is (29.4 +/- 10.3) ng/L, significantly higher than that of malignant pleural effusion (11.7 +/ 2.0) ng/L (P < 0.01). The sTNFR-I and sTNFR-II level in the serum of malignant pleural effusion is (1,132 +/- 303) ng/L and (1,548 +/- 489) ng/L respectively, significantly higher than that in tuberculosis pleural effusion which is (979 +/- 146) ng/L and (977 +/- 93) ng/L (P < 0.01) respectively. The sTNFR-I and sTNFR-II level in malignant pleural effusion is (1,404 +/- 306) ng/L and (2,195 +/- 418) ng/L respectively, markedly higher than those in tuberculosis pleural effusion which is (1,185 +/- 215) ng/L and (1,195 +/- 300) ng/L (P < 0.01). CONCLUSION: There are highly elevated TNF-alpha in tuberculosis pleural effusion; The sTNFR-I and sTNFR-II level in the serum and pleural effusion of malignant pleural effusion patients are significantly higher than those in tuberculosis pleural effusion patients, suggesting they may play some role in differentiating benign and malignant pleural diseases. PMID- 11778491 TI - [Transforming growth factor-beta immunogenic participating in tuberculous pathogenesis]. PMID- 11778490 TI - [Delayed type hypersensitivity responses to recombinant mycobacterial antigen 38,000 in guinea pigs sensitized to Mycobacterium tuberculosis]. AB - OBJECTIVE: To evaluate the ability and influencing factors that recombinant 38,000 antigen induces delayed-type hypersensitivity(DTH) reaction in guinea pigs. METHODS: In one skin test, physiological saline as negative control and PPD as positive control, guinea pigs were shaved on the back and given intracutaneous injection with 0.1 microgram, 0.2 microgram, 0.4 microgram of recombinant 38,000 antigen. Skin reactions were measured 48 h after antigen injection, each measuring two transverse diameters of the induration. In the other skin test, each guinea pig was intracutaneously injected in four sites, respectively with 5 IU PPD and recombinant 38,000 antigen (0.1 microgram, 0.2 microgram and 0.4 microgram) or 5 IU PPD and biantigen(combination 38,000 with 16,000 antigen, 0.1 microgram, 0.2 microgram and 0.4 microgram). Single antigen and biantigen were tested in three separate experiments. Each experiment needs six sensitized guinea pigs. Skin reactions were measured 24 h, 48 h and 72 h after antigen injection. RESULTS: DTH responses induced by 0.4 microgram were weaker than 0.1 microgram and 0.2 microgram in 24 h. 0.1 microgram and 0.2 microgram elicited DTH responses similar in strength to that of 5 IU PPD. From 0.1 to 0.4 microgram, similar dose of recombinant 38,000 antigen and combination antigen elicited similar DTH responses. DTH responses induced by recombinant 38,000 antigen had better be measured at 48 h, however that induced by combination antigen at 24 h. CONCLUSIONS: Recombinant 38,000 antigen can induce DTH responses in guinea pigs. Dose of antigen is important factor that affect DTH responses in guinea pigs. PMID- 11778492 TI - [Research on immunologic mechanism of antituberculosis protection]. PMID- 11778493 TI - [Changes of pulmonary diffusing capacity in subjects with acute mountain sickness]. AB - OBJECTIVE: The study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). METHODS: According to international definition of AMS (Lake Louise Consensus) thirty-two subjects were divided into AMS and non-AMS group. The pulmonary diffusion capacity for carbon monoxide (DLco) by the single-breath method, arterialized capillary blood gas were measured in all subjects at an altitude of 2,260 m and after ascent to 4,700 m. RESULTS: All subjects exhibited an increase in DLco from 2,260 m to 4,700 m, the degree of increase in DLco in the AMS group was significantly lower than that of the non-AMS group, delta DLco (1.3 +/- 1.7) ml.min-1.mm Hg-1 vs (10.7 +/- 1.3) ml.min-1.mm Hg-1 (P > 0.01). The AMS group showed a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DLco showed a significantly negative correlation with AMS score (r = -0.885 P < 0.01). CONCLUSIONS: These results suggest that the decreased pulmonary diffusing capacity has an important role in the incidence of acute mountain sickness, it reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung. PMID- 11778494 TI - [Strengthen research on drug-resistant tuberculosis]. PMID- 11778495 TI - [Primary drug-resistance of Mycobacterium tuberculosis in Shanghai, 1985-1995]. AB - OBJECTIVE: To evaluate the problem of antituberculosis drug resistance in Shanghai, 1985-1995. METHOD: All of the strains of M. tuberculosis from new patients with pulmonary tuberculosis were tested for resistance to INH, RFP, EMB, SM, PAS, and KM by the absolute concentration method on Lowenstein-Jensen medium. RESULTS: The rates of primary drug resistance to SM, INH, RFP, PAS, and KM were 10.2%, 5.2%, 4.8%, 5.6%, and 3.9% respectively in 1985, and decreased to 4.8%, 4.8%, 4.3%, 3.6%, and 2.6% in 1995, while the rate of drug resistance to EMB was 1.3% in 1985, and increased to 3.3% in 1995. The primary resistance rate to one or more drugs was 15.6% in 1985 and 8.2% in 1995. The resistance rates to one, two, three, four, five, and six drugs were 5.9%, 4.6%, 2.5%, 1.5%, 0.4%, and 0.8% respectively in 1985, and decreased to 1.9%, 3.5%, 1.2%, 1.2%, 0.1%, and 0.4% in 1995. The resistance rates to INH and RFP were 1.9% in 1992-1993, 2.4% in 1994 1995. CONCLUSION: The primary drug resistance of M. tuberculosis in Shanghai, 1985-1995, was in a trend of decline, but multi-drug resistance is still seriously existed. PMID- 11778496 TI - [Immunotherapeutic effect of Mycobacterium vaccae on multi-drug resistant pulmonary tuberculosis]. AB - OBJECTIVE: To evaluate the immuNotherapeutic effect of M. vaccae on multi-drug resistant (MDR) pulmonary tuberculosis. METHODS: 90 cases of MDR pulmonary tuberculosis with bacteriological positive were divided into immunotherapy (M, 28 cases), control (C, 28 cases) group at random pair and self control (S, 34 cases) group. The group M were treated by chemotherapy and M. vaccae for 6 months, the group C only treated by chemotherapy for 6 months, while group S only by chemotherapy in the first 3 months and in combination with M. vaccae in the next 6 months. RESULTS: After 6 months, the sputum negative conversion rates of group M were 43% in smear positive cases and 46% in culture positive cases, both of which were significant higher than those of group C (21%, 18%, P < 0.01). The sputum negative conversion rates of group S were 3%, 3% in smear and culture positive cases after 3-month chemotherapy, which increased to 44%, 41% respectively when M. vaccae was added for 6 months. Compared with group C, group M was better in improving of X-ray manifestation and cell-mediated immunity and closing of cavity (P < 0.05). The bacteriological relapse rates in group M, C, S were 8%, 20% and 7% respectively. CONCLUSION: As a adjunct to chemotherapy, M. vaccae is helpful for patients with MDR pulmonary tuberculosis by improving the cell-medicated immunity, sputum negative conversion and X-ray manifestation. PMID- 11778497 TI - [Drug susceptibility testing for M. tuberculosis with proportion method]. AB - OBJECTIVE: To analyze the feasibility of proportion method in drug susceptibility testing (DST) of M. tuberculosis(MTB). METHODS: DST was performed to 360 strains of MTB using proportion method and absolute concentration method, 30 of them using both China made and Sigma produced anti-TB drugs. MIC was detected in 19 strains whose results were different from standard ones. RESULTS: In isoniazid (INH) and ethambutol (EMB), the resistance rate and the accordance rate compared with standard results were significantly higher in proportion method than absolute concentration method (P < 0.01). But in streptomycin (SM) and rifampicin (RFP), they did not show any significant difference. The accordance rates of INH, SM, EMB and RFP between two methods were 81.1%, 92.5%, 83.6% and 98.6%. The DST results using China made and Sigma produced anti-TB drugs had no significant difference. CONCLUSIONS: The main reason made proportion method differ from absolute concentration method is critical concentration of drugs. China made anti TB drugs are also qualified for DST purpose. PMID- 11778498 TI - [Study on beta 2 adrenergic receptor genetic polymorphisms in asthmatics in the people of the Han nationality of northern China]. AB - OBJECTIVE: To analyze the association between beta 2-AR genetic polymorphism and asthma in the people of the Han nationality of northern China. METHODS: Allele Specific-PCR techniques were used to determine 16, 27 and 164 locus alleles of beta 2-AR genetic polymorphisms in 58 unrelated patients with asthma and 89 healthy controls from the people of the Han nationality of northern China. RESULTS: (1) The distribution frequency of genotype beta 2-AR 16 loci: Arg/Arg genotype accounts for 13%, Arg/Gly 76% and Gly/Gly 11%. The beta 2-AR 27 loci: Gln/Gln genotype accounts for 36%, Gln/Glu 55% and Glu/Glu 9%. The beta 2-AR 164 loci: Thr/Thr genotype accounts for 30%, Thr/Ile 53% and Ile/Ile 17%. (2) The frequency of genotype beta 2-AR 16 loci in asthmatics: Arg/Arg genotype accounts for 24%, Arg/Gly 45% and Gly/Gly 31%. There was a significant increase in the frequency of Gly/Gly genotype in asthmatics compared with healthy group(OR = 4.0, 95% CI 1.7-9.7), but there was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 27 loci in asthmatics: Gln/Gln genotype accounts for 34%, Gln/Glu 56% and Glu/Glu 10%. There was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 164 loci in asthmatics: Thr/Thr genotype accounts for 10%, Thr/Ile 83% and Ile/Ile 7%. There was no significant difference in the frequency of Ile/Ile genotype in asthmatics compared with healthy group, and in the allele frequency of asthmatics compared with healthy group. In addition, our study reveals that beta 2-AR 16 locus genetic polymorphism is in association with asthmatic severity. CONCLUSIONS: These results suggest that beta 2-AR 16 locus genetic polymorphism is correlated with asthma severity in the people of the Han nationality of northern China. PMID- 11778499 TI - [A clinical analysis of 31 cases with pulmonary damage caused by scrub typhus]. AB - OBJECTIVE: To deepen the understanding of pulmonary damage caused by scrub typhus. METHODS: 31 cases of pulmonary damage caused by scrub typhus from 1993 to 1998 were reviewed with chest radiographs, chest B-ultrasound, etc. RESULTS: 44% cases with scrub typhus showed a pulmonary damage (31/70), in which 66% (20/31) had cough, 53% (16-31) had sputum, 53% (16/31) had rales and the most symptoms were mild. Chest X-rays: 45% (14/31) showed pulmonary interstitial lesion, 53%(16/31) pulmonary effusion lesion and 8 cases pleural lesion. 26% (8/31) of pleural effusion was confirmed by chest B-ultrasound. Respiratory failure was found in 5 cases. All cases were treated with chloramphenicol and(or) doxycyclinum and made a good recovery. CONCLUSION: The pulmonary damage caused by scrub typhus should be paid more attention to for avoiding misdiagnosis. PMID- 11778500 TI - [Pulmonologists should play a leading role in the development of critical care in China]. PMID- 11778501 TI - [Experimental study of partial liquid ventilation in rabbits with acute lung injury]. AB - OBJECTIVE: To observe the effectiveness of partial liquid ventilation (PLV) on gas exchange, pulmonary compliance (Cst), blood dynamics in the oleic acid (OA) induced acute lung injury (ALI) rabbits. METHODS: 24 healthy male New Zealand rabbits were randomly allocated to three groups and treated with various methods after OA acute lung injury model established. The study groups as follows: PEEP group with conventional mechanical ventilation (CMV) and PEEP, normal saline (NS) group with CMV, PEEP and NS, FDC group with CMV, PEEP and FDC. The parameters such as blood gases, Cst, circulation state were observed before and after treatment. RESULTS: In FDC group, PaO2 increased from (90 +/- 6) mm Hg to (232 +/ 26) mm Hg(P < 0.05), PaCO2 decreased from (52.1 +/- 2.8) mm Hg to (40.1 +/- 3.0) mm Hg (P < 0.05), Cst increased from (1.05 +/- 0.11) ml/cm H2O to (1.79 +/- 0.24) ml/cm H2O(P < 0.05). HR, MAP and CVP showed no significant changes after treatment compared with pretreatment values in FDC group. CONCLUSION: Pulmonary gas exchange and pulmonary compliance improved significantly during PLV in the ALI rabbits, without obvious influence on hemodynamic status. PMID- 11778502 TI - [Changes on the protein kinase C activity of alveolar macrophages in patients with idiopathic pulmonary fibrosis]. AB - OBJECTIVE: To study the changes on protein kinase C(PKC) activity of alveolar macrophages (AM) in patients with idiopathic pulmonary fibrosis(IPF). METHOD: The PKC activity of AM in 9 healthy volunteers and 15 patients with IPF was investigated by radioactivity measuring. RESULTS: The total, cytosolic and particulate fraction PKC activity of AM in bronchoalveolar lavage fluid(BALF) from patients with IPF were higher than those from control group(P < 0.01 and P < 0.05). The total and the membrane fraction PKC activity had positive correlation with the number of cells in BALF(r = 0.8135, P < 0.01 and r = 0.5917, P < 0.05) respectively. CONCLUSION: As a bypass of transmembrane signal transduction, PKC was suggested to be involved in the development of IPF. PMID- 11778503 TI - [Thrombosis diseases and lung cancer]. AB - OBJECTIVE: To increase the awareness of lung cancer complicating thrombosis disease(TD). METHODS: 20 cases of lung cancer with TD which were from 1,050 cases of lung cancer confirmed by pathology and cytology in 80's and 90's from a teaching hospital were retrospectively reviewed. RESULTS: Of the 20 cases, there were 8 cases complicated with deep venous thrombosis(DVT); 4 cases with pulmonary thromboembolism (PTE); 4 cases with DVT and PTE, and 4 cases with nonbacterial thrombotic endocarditis (NBTE). 6 cases of DVT/PTE occurred 2-6 months before detection of lung cancer, 3 cases of NBTE had brain and peripheral artery embolism 2-7 months before detection of lung cancer. The pathology of 12 cases of lung cancer with TD was adenocarcinoma. CONCLUSIONS: TD complicating lung cancer was not unusual and could be warning sign indicating occult lung cancer. Physician ought to alert to lung cancer or other cancers when facing aged healthy subjects of sudden TD under unknown origin. The most common physiologic type of lung cancer complicating TD was adenocarcinoma. Hypercoagulation state was the most important cause of TD complicating lung cancer. PMID- 11778504 TI - [Gene therapy with tumor suppressor gene p53 and(or) p16 on the nude mice models of NSCLC in vivo]. AB - OBJECTIVE: To investigate the effect of tumor suppressor gene p53 and(or) p16 treatment on the nude mice models of non-small cell lung cancer (NSCLC). METHODS: Nude mice were injected subcutaneously with NSCLC cell line A549. 25 nude mice were randomly divided into 5 groups (control, SA, p53 gene, p16 gene, p53 + p16 genes), p53 and(or) p16 genes mediated by stearylamine/DOPE (SA liposome) were injected intratumorally alone or jointly. The size of tumor and survival period of nude mice were measured after treatment. RESULTS: p53 and(or) p16 genes can obviously inhibit the growth of tumor. The difference was significant between control and treated groups, among which the combined p53 and p16 genes enhance the inhibiting effect more markedly. The survival period of tumor-bearing nude mice was prolonged after transfecting p53 gene or p16 gene alone, p53 and p16 genes jointly can prolong the survival period significantly. CONCLUSIONS: Tumor suppressor gene p53 and(or) p16 in the replacement therapy of NSCLC are of potential clinical significance. The combination of p53 and p16 gene may have a greater antitumoral effect in vivo. PMID- 11778505 TI - [NF-kappa B activation and the inhibitory effect of dexamethasone in experimental asthmatic guinea pigs]. AB - OBJECTIVE: To investigate the role of NF-kappa B in pathogenesis of asthma. METHODS: Electrophoresis mobility shift assay and supershift assay were used to analyze the expression of NF-kappa B activation and its components. RESULTS: Nuclear extracts prepared from the thoracic blood mononuclear cells and the whole lung tissue, respectively in OVA-sensitized and challenged guinea pigs, both displayed stronger DNA-binding activity at 2 h timepoint (244.1 +/- 2.4; 176.0 +/ 4.0) comparing to the control (167.0 +/- 4.6; 67.3 +/- 2.5), and the activity peaked at 6 h timepoint (294.7 +/- 3.2; 282.3 +/- 6.8) and continued till 12 h timepoint (200.9 +/- 1.2; 110.8 +/- 1.0). The activated NF-kappa B contained p50. Dexamethasone suppressed the NF-kappa B activation (235.4 +/- 3.3; 104.6 +/- 8.4) in the nuclear extracts of the Blood mononuclear cells and the lung tissue, respectively. CONCLUSIONS: This result showed that NF-kappa B were possibly through transcriptionally regulating the expression of many important inflammatory proteins. The dexamethasone could inhibit the activation of NF-kappa B in the allergic model, possibly through which the antiinflammatory action was exerted. PMID- 11778506 TI - [The changes of guanylin in plasma and lung tissue from asthmatic guinea pigs]. AB - OBJECTIVE: To study the changes of guanylin in asthmatic guinea pig models. METHODS: Male guinea pigs were randomly divided into two groups: the control (n = 6) and the asthma group (n = 10). The levels of guanylin in plasma, BALF and lung tissue were measured by RIA kit. The mean thickness of airway wall and glands was determined by contour tracing, using a digitizing pad and microcomputer. RESULTS: The levels of guanylin in plasma and lung tissue from the asthma group were 56% and 183% higher than those of the control (P < 0.01). Concentrations of guanylin in BALF from the control were below the detection level in 4 guinea pigs, and 1.7 pg/ml and 1.6 pg/ml in two, respectively. The level of guanylin in BALF from asthma group was (3.1 +/- 1.2) pg/ml. The level of guanylin in the lung tissue correlated with that in plasma and BALF (r = 0.72, P < 0.01, r = 0.61, P < 0.05, respectively). The level of guanylin in plasma did not correlate with those of BALF (r = 0.32, P > 0.05). The mean thickness of airway wall and glands in asthma group were 86% and 87% greater than those of the control respectively (P < 0.01). The level of guanylin in lung tissue correlated with the thickness of glands (r = 0.95, P < 0.01). CONCLUSIONS: In the guinea pig model of asthma, guanylin in plasma, BALF and lung tissue were increased, indicating that it may play a role in the mechanism of airway hypersecretion in asthma. PMID- 11778507 TI - [High risk factors lead to noscomial pulmonary infections caused by MRSA]. AB - OBJECTIVE: To investigate major risk factors leading to death by noscomial MRSA pulmonary infections. METHOD: The data of hospitalized patients diagnosed as noscomial MRSA pulmonary infections were sorted out and analyzed for recent three years. RESULTS: Case mortality of 64 patients with noscomial MRSA pulmonary infections were 44%. Of these, 18 cases complicated fungi, 11 Klebsiella pneumoniae, 9 Pseudomonas maltophilia and 7 Enterococcus. Case mortality of fungi and Pseudomonas maltophilia were 67% and 61%, respectively. 23 cases had fever, 18 died (case mortality 78%) and 41 had no fever, 10 died (case mortality 24%) (chi 2 = 15.253, P < 0.005). The case mortality with reduction, normal and increase of leukocyte were 80%, 24% and 45%, respectively. The comparison between three groups had obvious significance (chi 2 = 12.554, P < 0.005) and the case mortality of leukocytopenia was higher than that of other two groups (chi 2 = 8.626, P < 0.005). The case mortality of hypoproteinemia was higher than that of the control group (chi 2 = 6.914, P < 0.01). The patients who developed fulminant lesions in liver, kidneys and lungs showed higher mortality rate. CONCLUSIONS: Case mortality of noscomial pneumonia caused by MRSA is very high. In addition to common causes, underling diseases, leukocytopenia, malnutrition and complex infections are also risk factors of MRSA infection. PMID- 11778508 TI - [127 cases of pulmonary fungal infection]. AB - OBJECTIVE: To find out the clinical features, therapeutic outcome, prognosis and the major predisposing diseases of pulmonary fungal infection(PFI). METHOD: 127 cases with PFI were retrospectively analyzed. RESULTS: Various predisposing diseases were found in 95% of total cases, among them, COPD, systemic lupus erythromatus(SLE), leukemia and chronic renal disease were main predisposing diseases. Primary pulmonary fungal infection was rare. All the clinical manifestations of PFI were not specific, reontgenographic features showed mainly bronchitis type(61%). Monilia (Candida) was ranked the first pathogen (79.5%). The mortality of PIF was high. Chronic renal and hematological diseases might be the risk factors for mortality (RR, relative rate, 5.14). CONCLUSIONS: PFI is an important cause of the secondary infection in many diseases. The clinical features of PFI is non-specific and the morbidity is rising. Clinicians should pay more attention to it. PMID- 11778509 TI - [Detection of extended-spectrum beta-lactamases and drug sensitivity test in clinical isolates of the family Enterobacteriaceae in Shanghai]. AB - OBJECTIVE: To investigate extended-spectrum beta-lactamases (ESBLs) production in clinical isolates of the family Enterobacteriaceae in Shanghai, and compare the resistant rates of ESBLs-producing strains and non-ESBLs-producing strains to 11 antibiotics. METHODS: Double-disk synergy test was used to detect ESBLs in 1,026 strains of the family Enterobacteriaceae; Kirby-bauer agar diffusion method was used to judge drug sensitivity. RESULTS: 34.31% of strains of the family Enterobacteriaceae were considered ESBLs producers by double-disk synergy test. The prevalences of ESBLs in isolates of Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae were 37.40%, 30.21% and 41.82% respectively. Except Imipinem and Cefmetazole, the resistant rates of ESBLs-producing strains to other 9 antibiotics were much higher than that of non-ESBLs-producing strains(P < 0.01). The resistant rates of Imipinem to ESBLs-producing strains were the lowest. CONCLUSIONS: The prevalence of ESBLs in clinical isolates of the family Enterobacteriaceae in Shanghai was high; it is necessary for clinical laboratory to detect ESBLs in clinical isolates of the family Enterobacteriaceae routinely. The resistant rates of ESBLs-producing strains to most antibiotics were high. Imipinem and Cefmetazole were the effective antibiotics to infections caused by ESBLs-producing strains. PMID- 11778510 TI - [Comparison of susceptibility testing results of M. tuberculosis by different methods]. AB - OBJECTIVE: To compare the susceptibility testing results of M. tuberculosis detected with different standards and methods. METHOD: 158 strains of M. tuberculosis isolated from clinical patients were detected for the drug sensitivity by Chinese standard and method (absolute concentration method), 1% resistance ratio and absolute concentration method of WHO/IUATLD standard. RESULTS: The drug-resistant rate detected by the standard of WHO/IUATLD was 53.8%(85/158), while by the Chinese standard 50.0%(79/158). The drug-resistant rates to INH, SM, EMB and RFP by WHO/IUATLD standard were 41.8%(66/158), 34.2%(54/158), 22.1%(35/158) and 27.8%(44/158) respectively, whereas by the Chinese standard 34.2%(54/158), 30.4% (48/158), 18.4%(29/158) and 27.2%(43/158) respectively. There was no significant difference between the results detected with WHO/IUATLD and Chinese standard, except for the results of INH. There was no significant difference between the results detected with WHO/IUATLD standard by 1% resistant ratio and absolute concentration methods. CONCLUSION: The results of drug-sensitivity were interfered by the detected standards but not by the tested methods. PMID- 11778511 TI - [Optic injury by ethambutol and its prophylaxis and treatment]. PMID- 11778512 TI - [The practicability of increasing exercise tolerance in mild to moderate asthmatic patients]. AB - OBJECTIVE: By performing the cardiopulmonary exercise testing in mild to moderate asthmatic patients and healthy volunteers, to assess the practicability of increasing exercise tolerance and improving life quality in the patients, and to assess the relationship between the resting IC and the maximal workload. METHODS: 19 mild to moderate asthmatic patients participating in the cardiopulmonary exercise testing with 19 health volunteers as controls. The incremental test was used. Forced expiratory volume in one second (FEV1) and inspiratory capacity (IC) were measured before the test and FEV1 measurements were repeated after exercise. Heart rate(HR), oxygen uptake(VO2), ventilation per minute(VE), breathing frequency(BF) were continuously measured during the test. RESULTS: There were changes of FEV1 after exercise in asthmatic patients [-(15.5 +/- 13.2)%] vs [+(1.7 +/- 2.7)%], (P < 0.05). They could achieve comparable VO2max (1.8 +/- 0.5) L/min vs (1.8 +/- 0.4) L/min, VEmax (29 +/- 7) L/min vs (31 +/- 5) L/min and O2 pulse max (0.0110 +/- 0.0020) L/beat vs (0.0110 +/- 0.0020) ml/beat with controls, but the BF at maximal exercise in asthmatic patients is significantly decreased (37 +/- 5) times/min vs (41 +/- 6) times/min, (P < 0.05). IC correlate with the maximum workload (r = 0.695, P < 0.05). CONCLUSION: The mild to moderate asthmatic patients had the same cardiopulmonary exercise response as the healthy volunteers, indicating that they did not have ventilatory and circulatory limitation to exercise. PMID- 11778513 TI - [Effect of low dose of inhaled corticosteroid combined with small dose of oral theophylline on treatment of bronchial asthma]. AB - OBJECTIVE: To investigate the effect of small dose of oral theophyllin combined with low dose of inhaled beclomethasone dipropionate (BDP) on clinical symptoms, bronchial responsiveness and hypothalamic-pituitary-adrenal axis (HPAA). METHODS: 43 patients with mild-moderate bronchial asthma were randomly divided into A and B groups. 21 subjects in group A were treated with oral substained release theophyllin (Protheo) (200 mg/night) and inhaled BDP (300 micrograms/day); 22 cases in group B received inhaled BDP (600 micrograms/day) and oral placebo. RESULT: Before and 13 weeks after the treatment, symptom scores, peak flow(PEF), and peak flow rate (PEFR) for group A were (1.8 +/- 0.9) and (0.10 +/- 0.30), (295 +/- 98) L/min and (444 +/- 150) L/min, (22 +/- 8)% and (9 +/- 3)% respectively, and those for group B were (1.90 +/- 0.70) and (0.10 +/- 0.30), (328 +/- 129) L/min and (441 +/- 146) L/min, (24 +/- 7)% and (9 +/- 3)% respectively, which were remarkably improved in both groups (P < 0.01), and bronchial provocation responsiveness to histamine tests (BHR) in both groups were also improved significantly (P < 0.01). There were no differences between two groups (P < 0.05). Frequency of using inhaled beta 2 agonist to relieve nocturnal asthmatic attacks in group B (3.9 +/- 1.7) was significantly greater than that in group A (1.3 +/- 1.0, P < 0.05). Plasma ACTH concentrations, basic cortisol levels and cortisol responses to ACTH before and 13 weeks after the treatment in group B were (31 +/- 13) ng/L and (20 +/- 8) ng/L, (95 +/- 50) micrograms/L and (86 +/- 48) micrograms/L, (156 +/- 98)% and (74 +/- 46)% respectively, which were decreased significantly after the treatment (P < 0.05). There were no such changes in group A. CONCLUSIONS: It was suggested that small dose of oral theophylline combined with low dose of inhaled BDP might have the same effect on relief of clinical symptoms and bronchial responsiveness, without suppression on HPAA function, comparing with relatively higher dose of inhaled BDP. PMID- 11778514 TI - [Correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE and eosinophilic cation protein]. AB - OBJECTIVE: To explore the correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE(sIgE) and eosinophilic cation protein(ECP). METHODS: Histamine inhalation provoking test (quantitative method) was used in a survey for bronchial responsiveress in 1,123 students aged between 11 to 14 years old, 41 individuals with asymptomatic bronchial hyperresponsiveness received further test for sIgE and ECP. 31 students with normal bronchial responsiveness were randomly selected as the control. RESULTS: 4%(41/1,123) of the students showed bronchial hyperresponsiveness. The incidence of bronchial hyperresponsiveness with family history of asthma (11/14, 79%) was higher than that without a family history (30/1,109, 3%), with statistical significance (P < 0.005). The positive rates for sigE (90%, 37/41, P < 0.01) and ECP (17%, 7/41, P < 0.05), sIgE q value (14.3 +/- 12.1) micrograms/L, (P < 0.01) and ECP value (44.3 +/- 60.2) micrograms/L, (P < 0.01) in asymptomatic bronchial hyperresponsiveness group were higher than those of the control with statistical significance. His PD20-FEV1 was negatively related to aIgE q value (P < 0.05) and not related to ECP (P > 0.05). CONCLUSION: The asymptomatic bronchial hyperresponsiveness was closely related to allergy but not to ECP. Those with a family history of asthma, or with positive sIgE should be followed. PMID- 11778515 TI - [The role of platelet activation in the pathogenesis of asthma]. AB - OBJECTIVE: To investigate whether platelets are activated during an asthmatic attack and to detect the correlation between platelet activation and severity of bronchial asthma. METHODS: Plasma concentration of thromboxane B2(TXB2) and 11 dehydro-TXB2(11-DH-TXB2) and P-selectin (CD 62P) on platelet surface were measured in 44 patients with asthma and in 18 normal individuals using ELISA and FCP. The serum ECP level and pulmonary function were also analysed. RESULTS: The plasma level of 11-DH-TXB2 and TXB2 and the positive percentage of CD 62P on platelets were significantly increased in patients with acute asthma (n = 28) as compared with the control (n = 18, P < 0.01). The plasma concentration of 11-DH TXB2 and TXB2 were decreased significanty after the control of asthma. The level of platelet activation was correlated with ECP (r = 0.785, P < 0.05), FEV1% (r = 0.867, P < 0.01) and PEF(r = -0.745, P < 0.05). CONCLUSIONS: These results suggest that there is an abnormal platelet activation in asthmatics, which can reflect the severity of bronchial asthma to a certain extent, although its exact, mechanism is unknown. The platelets secret a wide range of biologically active substances capable of inducing or augmenting the airway inflammatory responses in asthma. PMID- 11778516 TI - [The imbalance of Th1/Th2 cytokine expression in peripheral blood mononuclear cell from asthmatic patients and the effect of erythromycin on these cytokines]. AB - OBJECTIVE: To observe the state of Th1/Th2 cytokine expression in peripheral blood mononuclear cells (PBMCs) from asthmatic patients and the effect of erythromycin (Ery) on it. METHODS: 23 asthmatic patients and 10 healthy volunteers were included. The mRNA expression for Th1/Th2 cytokines in PBMC before and after the culture with Ery were detected by RT-PCR, considering IL-2 and IFN-gamma as Th1 cytokines, and IL-4, IL-6, IL-10 as Th2 ones. RESULTS: The positive rate of mRNA expression for Th2-derived IL-4, IL-6, IL-10 in the study group were 18/23, 19/23 and 10/23 respectively, and those for IFN-gamma and IL-2 produced by Th1 cells were 1/23 and 13/23, respectively. In the control group, the positive rate for IL-4, IL-6, IL-10 were 0/10, 2/10 and 1/10, respectively, and those for IL-2 and IFN-gamma were both 1/10. Comparing with the control group, the positive rate of mRNA expression for IL-4 and IL-6 in PBMC from asthmatic patients were significantly higher (P = 0.00003, 0.001 respectively). After the culture with Ery for 48 h, the positive rate for IL-4 expression in the study group decreased from 18/23 to 5/23 (P = 0.0006), and IL-6 from 19/23 to 9/23 (P = 0.006). The positive rate for IFN-gamma expression was elevated while IL-2 decreased(But both had no statistical significance). There was no difference observed before and after the culture with Ery in the control group. CONCLUSIONS: There is a predominant expression of Th2-type cytokines in PBMC from asthmatic patients. Ery can down-regulate the mRNA expression for IL-4 and IL-6 in asthmatic patients, and might convert the imbalance of Th1/Th2 cytokine expression in asthmatic patients. PMID- 11778517 TI - [The relationship of vasoactive intestinal peptide, other substances and the changes of nocturnal blood pressure in patients with obstructive sleep apnea syndrome]. AB - OBJECTIVE: To determine the difference of plasma VIP, NO and ET concentrations in awake and in different sleep periods and the relationship between VIP, NO and ET values and the changes in nocturnal blood pressure in patients with obstructive sleep apnea syndrome(OSAS). METHODS: Retaining manometric tube in radial artery and polysomnography(PSG) were done synchronously in 12 patients with OSAS whom was diagnosed by whole-night PSG. Blood specimens were collected before sleep, during NREM sleep and REM sleep and the next morning to detect the concentrations of VIP and ET by radioimmunoassay(RIA) and NO by nitrate reductase method. RESULTS: (1) Plasma NO values were significantly decreased in the morning than those before sleep (P = 0.014). There was no remarkable changes of VIP and ET values in different testing periods. (2) Plasma NO and ET values in the morning were correlated with hypoxia at night, but not with AHI (P > 0.05). (3) Plasma VIP values were significantly correlated with the baseline of SBP (r = 0.654, P < 0.05) and DBP (r = 0.706, P < 0.01) in NREM sleep and that of DBP (r = 0.613, P < 0.05) in REM sleep. There was no significant correlation between BP and plasma NO and ET values in different times. CONCLUSIONS: Endothelial dysfunction associated with NO reduction might be present and VIP might be involved in regulating BP changes in patients with OSAS. PMID- 11778518 TI - [Pulmonary lymphangioleiomyomatosis]. AB - OBJECTIVE: To improve the diagnosis and treatment of pulmonary lymphangioleiomyomatosis (PLAM). METHODS: Three patients with PLAM confirmed by pathological assessment were presented and relevant literatures were reviewed. RESULTS: PLAM is a rare pulmonary disease of unknown cause. The clinical manifestations were pneumothorax, exertional dyspnea and hemoptysis. Pulmonary function test showed obstructive or compound ventilative defect and hypoxemia. HRCT showed bilateral diffuse cystic airspaces change. Pathological features showed abnormal smooth muscle proliferation occurred along lymphatics. Lymphatics dilated and proliferated. CONCLUSIONS: The prognosis of PLAM is poor. There is no effective method for the treatment of this disease at present. PMID- 11778519 TI - [Therapeutic effect of interleukin-12 on murine infection with Mycobacterium tuberculosis through modulating Th1 and Th2 cytokine balance]. AB - OBJECTIVE: To study the effect of IL-12 on cytokines of murine infection with Mycobacterium tuberculosis. METHODS: 42 BALB/c mice infected with Mycobacterium tuberculosis were randomized into normal control (PBS) and IL-12 (n = 21) groups, treated with PBS or IL-12 respectively. Blood level of IFN-gamma, IL-4, and IL-10 were detected with ELISA method. The numbers of viable bacteria in organs were counted. Survival rate after treatment was investigated. RESULTS: In IL-12 group, none was dead. The numbers of viable bacteria in lung, liver and spleen were (227 +/- 107) x 10(5) cfu/ml, (4 +/- 3) x 10(5) cfu/ml and (1.5 +/- 0.5) x 10(5) cfu/ml respectively. INF-gamma (1,090 +/- 406) pg/ml. In PBS group, 8 mice were dead. The numbers of viable bacteria in lung, liver and spleen were (659 +/- 405) x 10(5) cfu/ml, (23 +/- 19) x 10(5) cfu/ml and (10.8 +/- 3.5) x 10(5) cfu/ml respectively. IFN-gamma (548 +/- 214) pg/ml. There was significant difference between those two groups. No change of the level of IL-4 in two groups. CONCLUSIONS: IL-12 induced IFN-gamma production, promoted development of Th1 cell responses, modulated Th1 and Th2 cytokine balance, suggesting that IL-12 enhance the host defense against the infection. PMID- 11778521 TI - [Exercise induced asthma]. PMID- 11778520 TI - [Pleural effusion of gout]. AB - OBJECTIVE: To investigate the lung complication of patients with gout. METHODS: Laboratory, radiation and pathology examining were exerted to 11 patients with gout and lung injury. RESULTS: Uric acid crystal was found in four patients pleural effusion and stones in two patients' spittle which were consist of monosodium urate (MSU). Uric acid salt crystal was found sputum in five patients as well as fibrosis was found in the patients' lung by radiation and pathology examination. CONCLUSIONS: The diagnoses of lung complications in eleven patients with gout were reliable. PMID- 11778523 TI - [Improve the diagnosis and treatment of pulmonary embolism]. PMID- 11778522 TI - [Molecular genetics of asthma]. PMID- 11778524 TI - [Pulmonary embolism due to deep venous thrombosis of extremities]. AB - OBJECTIVE: To study the relationship between pulmonary embolism and deep venous thrombosis of extremities. METHODS: The authors conducted a retrospective analysis of 100 patients with deep venous thrombosis to analyse the occurrence of pulmonary embolism during 1996 to and 1998 in their hospital. RESULTS: In the 100 patients with deep venous thrombosis, the complication of pulmonary embolism was 45%, fatal pulmonary embolism was 4%. CONCLUSION: The complication of pulmonary embolism in the patients with deep venous thrombosis frequently occurred and medical professionals should pay attention to them. PMID- 11778525 TI - [Expression of GM-CSE mRNA in asthmatic patients]. AB - OBJECTIVE: To explore non-invasive and specific markers for airway inflammation. METHODS: RT-PCR methods were used to measure GM-CSF mRNA expression in airway mucosa and induced sputum from asthmatic patients. The correlation was analyzed between expression of GM-CSF mRNA and eosinophils or other inflammatory cells. RESULTS: (1) The numbers of eosinophils and EG2 positive cells were (17.9 +/- 7.0) x 10(2) per mm2, and (8.9 +/- 3.0) x 10(2) per mm2 in the asthmatic group, significantly higher than those in the non-asthmatic control which were (1.9 +/- 1.0) x 10(2) per mm2, and (0.8 +/- 0.2) x 10(2) per mm2, respectively (P < 0.05). (2) The expression of GM-CSF mRNA was (1.4 +/- 0.6) in the asthmatic group, significantly higher than that in the control group (0.3 +/- 0.3) (P < 0.05), and GM-CSF mRNA expression was correlated with the numbers of EG2 positive cell (r = 0.73 and P < 0.05). (3) The percentage of eosinophils in induced sputum from asthmatic patients was (0.334 +/- 0.067), which was significantly higher than that from chronic bronchitis and control (0.021 +/- 0.004), (0.008 +/- 0.003) (P < 0.05). (4) The expression of GM-CSF mRNA in asthmatics was (0.320 +/- 0.054), significantly higher than that in chronic bronchitis and the control group (0.188 +/- 0.024 and 0.058 +/- 0.028) (P < 0.05). The expression of GM-CSF mRNA in patients with chronic bronchitis was also significantly higher than that in the control group (P < 0.05). CONCLUSIONS: The expression of GM-CSF mRNA in induced sputum may be a relatively specific marker for airway inflammation. PMID- 11778526 TI - [Role of peroxynitrite on airway hyperresponsiveness in asthmatic guinea-pigs]. AB - OBJECTIVE: To study the formation and localization of peroxynitrite(ONOO-) in the lung tissues of asthmatic guinea pig and investigate the effects of ONOO- on airway hyperresponsiveness in asthma. METHODS: 18 guinea pigs were randomly divided into three groups of 6 each: (1) asthmatic group: guinea pigs were injected intraperitoneally with 1 ml of 10% ovalbumin. After 14 days, the animals were exposed to aerosol of 1% OVA; (2) aminoguonidine (AG) group: Animal immunization was the same as above, but 1 h before the animals were exposed to OVA aerosol, 10 mg/kg AG were injected intraperitoneally. (3) control group. The formation and localization of ONOO- in the lung tissues of the guinea-pig asthma model were observed by immunohistochemical detection. The effect of exogenous ONOO- on contractions of isolated tracheal strips of the guinea-pigs to various concentrations of histamine was examined. The damage of airway epithelial cells induced by ONOO- was observed by electron microscopy. RESULTS: There was strong immunoreactivity for nitrotyrosine (NT), a specific marker of ONOO- formation in vivo, in the airway epithelial cells and inflammatory cells surrounding small airways of the guinea-pigs with asthma. The AG group showed significantly decreased number of NT positive cells in the lung tissues. There were only a few NT positive cells in the control group. The responsiveness of isolated tracheal strips to various concentration of histamine(except 10(-8) mol/L) in the ONOO- 0.5 mmol/L group were significantly increased compared with the vehicle group. (P < 0.05, P < 0.01 or P < 0.001). The sensitivity of isolated tracheal strips to histamine in the ONOO- 0.5 mmol/L group were also increased compared with the vehicle group(P < 0.001). Electron microscopical observation of the airways revealed airway epithelial injury and shedding. CONCLUSION: There was ONOO- overproduction in airway epithelial cells of asthmatic guinea-pigs, which may contribute to airway epithelial damage and hyperresponsiveness in asthma. PMID- 11778528 TI - [Bronchial hyperreactivity in patients with mitral stenosis and therapeutic effect of inhaled corticosteroids]. AB - OBJECTIVE: To assess the role of bronchial hyperreactivity (BHR) in patients with mitral stenosis and to evaluate the effect of inhaled corticosteroids in treating these patients. METHODS: Histamine bronchial provocation testing was performed in 23 patients with mitral stenosis. Patients with BHR were randomized into beclomethasone treatment and placebo group. Patients without BHR were also treated with beclomethasone as controls. RESULTS: 15 patients showed BHR. His PD20-FEV1 were significantly higher after 6 weeks treatment (P < 0.05), and symptom scores significantly lower(P < 0.05) in beclomethasone treatment group while remained unchanged in placebo group(P > 0.05). CONCLUSIONS: BHR is commonly found in patients with symptomatic mitral stenosis. Beclomethasone can significantly decrease bronchial reactivity to histamine and improve symptoms in patients with mitral stenosis. PMID- 11778527 TI - [A study on the relationship between viral infections and asthma in adults]. AB - OBJECTIVE: To study the relationship between viral infections and asthma in adults, and the mechanism that viruses lead asthma. METHODS: The sera from 130 adults of asthma and 20 normal controls are both tested for specific IgG and IgM of RSV, ADV3, ADV7, PIVI, PIVIII and CMV by an indirect ELISA, then the result is compared by chi 2 test. The RSV-IgM positive patients obtained from above and normal controls are both tested for RSV-IgE by the indirect ELISA and for titres of interferon(IFN) by microcytopathic-inhibiting-test, the results are both compared by t test. RESULTS: Almost all the patients have one or more viral infections, the highest infective rate is RSV, the total positive rates of IgG and IgM are 78%, compared with controls, chi 2 = 47.6, P < 0.00001. The acute infection can enhance asthma. From 17 patients of RSV-IgM positive, the sera titres of RSV-IgE are higher than controls apparently (t = 2.45, P < 0.05), IFN levels are lower than controls significantly (t = 2.83, P < 0.01). CONCLUSIONS: That asthma breaks out or becomes heavier in adults has close relationship with respiratory viruses infections, especially with RSV. Its mechanism is relative to the immune injury of viruses, hypersensitivity-type I and lower titres of immune regulating factor of IFN. PMID- 11778529 TI - [Study on respiratory impedance of patients with extratracheal tumour]. AB - OBJECTIVE: To determine the manifestation of impulse oscillometry (IOS) in variation of respiration impedance on patients with extratracheal tumour. METHODS: The IOS indices in 30 normal persons and 28 patients with extracheal tumour were measured. The ratio of forced expiratory volume after 1 second to forced vital capacity (FEV1/FVC) was evaluated and the maximal expiratory flow volume curve (MEFV curve) was examined. The above values with t-test of SPSS statistics software were analyzed. RESULTS: Compared with the normal group, in the extratracheal group the ratio of actual value of resistance to the predict from 20 Hz to 35 Hz increased obviously and this only occurred with the reactance at 20 Hz (P < 0.01). The resistance curve showed clear rise after the 20 Hz and the reactance curve peaked at 20 Hz and was leveled to normal at 35 Hz. CONCLUSION: IOS is capable of presenting the distinctive indices for the study of respiration impedance on patients with extratracheal tumour. PMID- 11778530 TI - [Local chemotherapy by fibrobronchoscopy for advanced bronchogenic carcinoma]. AB - OBJECTIVE: To observe the effectiveness of treatment in the patients with advanced bronchogenic carcinoma of local chemotherapy with fibrobronchoscopy, combined with systematic chemotherapy. METHODS: 40 patients with advanced bronchogenic carcinoma were divided into the tested group (20 patients) and the control group (20 patients) randomly. By fibrobronchoscopy with its matched injecting needle, carboplatin 300 mg were injected into the centre of the tumor and the surroundings, combined with the routine carboplatin and etoposide (CE) regimen. While the control group was treated only by intravenous chemotherapy with the routine CE regimen. RESULTS: In the 20 patients with local chemotherapy by fibrobronchoscopy combined with intravenous chemotherapy, 7 cases (35%) were completely cured and 11 cases (55%) showed partial recovery, other 2 cases without change. The 90% effective rate was significantly higher than 55% of the control group (P < 0.05). CONCLUSIONS: The local chemotherapy by fibrobronchoscopy can remarkably reduce the size of tumor, and relieve symptom of dyspnea. Intravenous chemotherapy alleviated the obstruction caused by tracheal or bronchial neoplasms. The combined therapies led to much better therapeutic effect and symptomatic relief than those by the routine CE regimen. PMID- 11778531 TI - [Alteration of interferon-gamma and interleukin-12 released by bronchoalveolar lavage cells from pulmonary tuberculosis]. AB - OBJECTIVE: To explore the change of cytokine released in bronchoalveolar lavage fluid (BALF) cells from pulmonary tuberculosis (TB) patients. METHODS: BALF cells were obtained from group A: 10 normal control volunteers (normal control group); group B: 10 radiographically uninvolved sites of pulmonary TB patients (uninvolved sites group); group C: radiographically involved two lobes of lung and smear-positive of 10 pulmonary TB patients with an onset less than one year; and group D: radiographically involved more than three lobes and smear-positive of 10 pulmonary TB patients with an onset longer than two years. The IFN-gamma and IL-4 production in the culture supermate of BALF lymphocytes stimulated with PHA and IL-12 production in the culture supermate of BALF macrophage (AM) stimulated with lipopolysaccharide were determined using sandwich ELISA. RESULTS: In group C, the IFN-gamma and IL-12 levels [(834 +/- 101) and (294 +/- 73) ng/L, respectively] were not only significantly higher than those of the group B[(197 +/- 59) and (67 +/- 23) ng/L, respectively, all P < 0.01] and normal control group[(179 +/- 51) and (57 +/- 24) ng/L, respectively, all P < 0.01], but also significantly higher than those of group D[(431 +/- 169) and (121 +/- 63) ng/L, respectively, all P < 0.01]; in group D, the IFN-gamma and IL-12 levels were significantly higher than those of the group B and normal control group (all P < 0.01); there were no significant differences between the group C and normal control group (P > 0.05); no differences were seen in IL-4 level among the 4 study groups. CONCLUSIONS: A TH1 type response occurs in involved sites of pulmonary TB patients and that may result from AM which as a regulator through production of IL-12, and the TH1 type response may affect presentation and outcome in pulmonary TB. PMID- 11778532 TI - [Detecting mycobacteria and their L-forms in peripheral blood from pulmonary tuberculosis patients by cultivation with hemolyzed-centrifugated blood in liquid medium]. AB - OBJECTIVE: To establish a new method of detecting mycobacteria and their L-forms in blood. METHODS: 65 samples of peripheral blood from patients with pulmonary tuberculosis were cultivated directly or cultivated with hemolyzed-centrifugated blood sediments in 92-3TB and 92-3TBL liquid medium, and the cultures were staining with immunoenzyme technique (ABC method). RESULTS: In 65 specimens, the positive rates of mycobacteria and their L-forms were 15%, 26% respectively with total isolation rate of 32%. In cultivating with hemolyzed-centrifugated blood the positive rate was much higher than direct cultural method (P < 0.05). In sputum the positive rates of acid-fast bacilli and their L-forms were 38% and 20% respectively, with total isolation rate of 52%, higher than that in peripheral blood (P < 0.05), and the total positive rate of combinative detection of blood and sputum salmples was 65%. CONCLUSIONS: Mycobacteria and their L-forms exist in peripheral blood of patients with pulmonary tuberculosis, and mainly in L-forms. Cultivation with hemolyzed-centrifugated blood in liquid medium and staining with immunoenzyme technique are valuable in routine detection of mycobacteria and their L-forms in peripheral blood. The positive rate of bacterial culture of pulmonary tuberculosis could be increased in combination with sputum mycobacteria and their L-forms examination. PMID- 11778533 TI - [Study on pathogenicity of sputum from cavity of sputum negative patients with pulmonary tuberculosis after short course chemotherapy]. AB - OBJECTIVE: To find out whether or not the sputa of pulmonary tuberculosis(PTB) patients with cavitation but sputum negative have pathogenicity after short course chemotherapy. METHODS: Guinea pigs were inoculated with sputa of PTB patients who were with cavitation but sputum negative after having finished short course chemotherapy. Then their body weight, enlargement of local lymph nodes and other ordinary symptom were observed. Six weeks later, pathological changes of TB in the internal organs were examined by dissecting these guinea pigs. Culture and drug resistance test of tubercle bacillus were also conducted. All of which were with negative and positive controls. RESULTS: Of the 63 cases included, 3(5%) patients' sputa resulted in tuberculous nodulation varying in amount in lung, liver and spleen of these guinea pigs, and the culture for tubercle bacillus of these sputa was positive too. CONCLUSIONS: 5% of sputum collected from PTB patients with cavitation but sputum negative still show pathogenicity after short course chemotherapy. For the cases with drug-resistant PTB and slow sputum negative conversion, the treatment should be prolonged and tubercle bacilli in their sputa should be monitored. PMID- 11778534 TI - [Recent advance in the diagnosis and treatment of pulmonary embolism]. PMID- 11778535 TI - [Changes of plasma p-selectin and nitric oxide in patients with pregnancy induced hypertension]. AB - OBJECTIVE: To study the roles of P-selectin and nitric oxide (NO) on the etiology of pregnancy induced hypertension (PIH). METHODS: The levels of plasma P-selectin and nitrite and nitrate (NO2-/NO3-) were determined in 36 patients with PIH. The data were compared with those of normal pregnant group (n = 18) and healthy non pregnant group (n = 19). The levels of plasma P-selectin were measured by means of enzyme-linked immunosorbent assay (ELISA) and levels of plasma NO2-/NO3- were measured by Griess reaction after the nitrate was reduced by a Cadmium-reduction method. RESULTS: The result showed: (1) The level of P-selectin in the normal pregnant group (48.92 +/- 15.16) micrograms/L was higher than that in non pregnant group [(30.16 +/- 8.42) micrograms/L, P < 0.001]. There was no significantly statistical difference in the levels of P-selectin between the normal pregnant group and the mild PIH group (P > 0.05). The levels of P-selectin in the moderate and severe PIH group (70.11 +/- 17.65) micrograms/L were higher than those in the mild PIH group [(47.33 +/- 17.95) micrograms/L, P < 0.01] and the normal pregnant group (P < 0.001). (2) The concentration of NO2-/NO3- in normal pregnant group was higher than that in non-pregnant group (P < 0.01). The concentration of NO2-/NO3- in PIH group were lower than was in normal pregnant group (P < 0.001). The NO2-/NO3- in mild group was lower than that in normal pregnant group (P < 0.001). The Plasma concentration of NO2-/NO3- in moderate and severe PIH group was lower than that of mild group (P < 0.05). (3) There was a negative correlation between the plasma concentration of P-selectin and NO2-/NO3- in the PIH group. CONCLUSION: The changes of plasma levels of P-selectin and NO are related to the occurrence and development of PIH. PMID- 11778536 TI - [Study on the relation between the angiotensin converting enzyme gene and pregnancy induced hypertension]. AB - OBJECTIVE: To study the relationship between the 16th intron insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and pregnancy induced hypertension (PIH). METHODS: The 16th intron I/D polymorphism of ACE gene in 60 PIH women (PIH group) and 50 normal pregnant women (control group) was detected by PCR. The type of ACE gene in PIH group was assessed and the serum concentration of angiotensin II (AngII) was compared between PIH group and control group. RESULTS: ACE gene types in the PIH women included: insertion homozygote II, deletion homozygote (DD) and insertion/deletion heterozygote (ID). The gene frequency was 55.0% (33/60) for II, 26.7% (16/60) for ID and 18.3% (11/60) for DD respectively. The frequency of insertion allelotype (0.7) of PIH group was higher than that of control group (0.3) (P < 0.05). The Ang II concentration in DD type PIH women was higher than that in control group although the Ang II concentration in II type and I D type PIH was not different from control. CONCLUSIONS: ACE gene polymorphism in the PIH women included: insertion homozygote II, deletion homozygote (DD) and insertion/deletion heterozygote (ID). The concentration of Ang II in DD type PIH women was higher than in control. It is suggested that the pathogenesis of PIH may be connected with multiple genes and factors. PMID- 11778537 TI - [Determination of serum soluble interleukin-6 receptor and soluble gp130 levels in patient with pregnancy induced hypertension and its significance]. AB - OBJECTIVE: To observe the changes of serum soluble interleukin-6 receptor (sIL 6R) and soluble gp130 (sgp130) in patients with pregnancy induced hypertension. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to determine serum sIL-6R and sgp130 levels in 40 patients with pregnancy induced hypertension (study group), 20 normal non-pregnant women (control group I) and 20 normal pregnant women (control group II). RESULTS: In study group, sIL-6R was (196.7 +/- 12.9) micrograms/L and sgp130 was (379.4 +/- 79.3) micrograms/L. In control group I, sIL-6R was (174.8 +/- 46.2) micrograms/L and sgp130 was (273.6 +/- 28.3) micrograms/L. In control group II, sIL-6R was (174.4 +/- 48.3) micrograms/L and sgp130 was (254.4 +/- 34.7) micrograms/L. SIL-6R and sgp 130 were higher in study group than those in control groups with significant difference (P < 0.01). In study group, the more severe the patients, the higher the sIL-6R and sgp130 levels. There was significant difference (P < 0.01). There was no difference in sIL-6R and sgp130 levels between control groups (P > 0.05). CONCLUSIONS: Serum sIL-6R and sgp130 levels are related to the development of pregnancy induced hypertension. PMID- 11778538 TI - [Role of costimulating molecule CD86 in maternal-fetal immune regulation]. AB - OBJECTIVE: To evaluate the role of costimulating molecule CD86 in maternal-fetal immune regulation. METHODS: In abortion-prone (CBA x DBA/2) matings and non abortion-prone (CBA x BALB/c) matings, the pregnant CBA females were injected intraperitoneally by purified rat anti-murine CD86 monoclonal antibody (mAb) with dosage of 100 micrograms at day 4, 6, 8 and 10 of gestation respectively, or injected only once at day 4 of gestation, or injected with purified rat IgG as control. The resorbing and non-resorbing embryos were enumerated at day 14 of gestation. RESULTS: The embryo resorbing rate in CBA x DBA/2 matings was 27.78%, and that in CBA x BALB/c matings was 8.42%. After injection of anti-CD86 mAb at day 4, 6, 8, 10 of gestation, the embryo resorbing rate reduced to 9.68% (P < 0.005) in CBA x DBA/2 matings, while that was 13.54% in CBA x BALB/c matings (P > 0.05). After injection of anti-CD86 mAb only once at day 4 of gestation, the embryo resorbing rate reduced apparently to 7.14% (P < 0.001) in CBA x DBA/2 matings, while that was 11.39% (P > 0.05) in CBA x BALB/c matings. CONCLUSIONS: Blocking the costimulating signal by anti-CD86 mAb at maternal-fetal interface, especially at the prime stage of maternal-fetal recognition (periods of implantation), may result in maternal-fetal tolerance, and hopefully the embryo resorption turns to normal pregnancy. PMID- 11778539 TI - [The relationship between maternal infection with human parvovirus B19 and fetal death and congenital malformation]. AB - OBJECTIVE: To study the relationship between matanal infection with human parvovirus B19 and fetal death and congenital malformation. METHOD: B19-DNA was detected by Polymerase Chain Reaction (PCR) in blood samples from 335 pregnant women. The pregnant outcomes were followed. RESULTS: In 335 pregnant women, 67 cases were B19-DNA positive and 268 cases were B19-DNA regative. There were four fetal deaths and one anencephalus in B19-DNA positive group. There was no fetal deaths or congenital malformation in B19-DNA negative group. The difference is significant (P < 0.05). CONCLUSIONS: Maternal infection with human parvovirus B19 may contribute to fetal death and congenital malformation. PMID- 11778541 TI - [Relationship of abnormal umbilical artery flow velocity waveforms and placental pathology]. AB - OBJECTIVE: To investigate the relationship of abnormal umbilical artery (UmA) flow velocity waveforms (FVWS) with placental weight, volume and all classes of villi and vessels. METHODS: Ten IUGR with abnormal umbilical artery(AA) were set as pathological group. Ten normal weight births with abnormal UmA FVWS(AN), 10 IUGR with normal UmA FVWS (NA), 10 normal weight births with normal UmA FVWS (NN) were selected as controls. Anti-alpha-SMA antibody was used to examine placental stem vessels and stem villi. The placental weight, volume, numbers of all classes of villi and vessels were compared. RESULTS: (1) Placental weight and volume in pathological group reduced significantly, while compared with AN (P < 0.01, P < 0.05, respectively), NA (P < 0.01, P < 0.001, respectively), and NN (all the P values < 0.001). (2) When the pathological group was compared with other 3 control groups with respect to the numbers of all classes of villi and vessels in placenta, the number of stem vessels reduced significantly (P < 0.05, P < 0.01, P < 0.001 respectively). The number of stem villi reduced significantly, compared with NA and NN (P < 0.01, P < 0.001, respectively). The number of stem villi did not change when compared with AN (P > 0.05). CONCLUSION: Abnormal UmA FVWS is related with placental weight, volume, all classes of villi and vessels. The reduction of villous and vascular number may be due to arrest of placental angiogenesis but not selective obliteration of vessels. PMID- 11778540 TI - [Effect of mifepristone on the expression of tumor necrosis factor-alpha and transforming growth factor-beta in decidua of early pregnancy]. AB - OBJECTIVE: To investigate the effect of mifepristone on the expression of tumor necrosis factor-alpha(TNF-alpha) and transforming growth factor-beta(TGF-beta) in decidua of early pregnancy. METHODS: Thirty artificial abortion women as control and thirty drug abortion women were enrolled for study. The expressions of TNF alpha and TGF-beta in decidua were measured with immunohistochemical method. RESULTS: There was no significant difference of TNF-alpha positive expression rates between drug abortion group (73.33%) and artificial abortion group (70.00%, P > 0.05). TGF-beta expression rate of drug abortion group was similar to that of artificial abortion group. The highly-positive (++ and +++) TNF-alpha expression rate in drug abortion group was significantly higher than that in artificial abortion group (P < 0.05). TGF-beta expression degree in decidua of drug abortion group was significantly lower than that of artificial abortion group (P < 0.05). The ratio of TNF-alpha/TGF-beta in drug abortion group is higher than that in artificial abortion group. CONCLUSION: TGF-beta has great effect on regulating the embryo development of early pregnancy. The change of TNF-alpha may be the reason of abortion. Mifepristone may interfere with embryo growth by inhibiting the activity of TGF-beta or by stimulating the secretion of TNF-alpha. PMID- 11778542 TI - [Correction of polypronuclear zygotes in 31 cases by micromanipulation]. AB - OBJECTIVE: To study the development of polypronuclear zygotes corrected by micromanipulation. METHODS: Thirty one cases of polypronuclear zygotes were corrected during September to December of 1999 through micromanipulation to remove supernumerary pronucleus from polypronuclear zygotes at 37 degrees C and observing their development 24 and 48 hours later to compare with the normal pre embryos. RESULTS: 17 in 31 (55%) cases of corrected polypronuclear zygotes developed to 2 to 4-cell pre-embryoes 24 hours later. There was significant difference while compare with the normal zygotes. However 48 hours later the cleavage rate of the two group of preembryos was the similar. CONCLUSION: The correction of polypronuclear zygotes by micromanipulation may in some way cause damage to the cleavage ability in part of the zegotes, but the remaining can develope normally. PMID- 11778543 TI - [Effect of growth hormone on the outcome of ovulation induction in patients with polycystic ovary syndrome]. AB - OBJECTIVE: To study the effect of growth hormone (GH) on the outcome of ovulation induction in patients with polycystic ovary syndrome (PCOS). METHODS: We examined serum sex hormone, GH and insulin like growth factor-II (IGF-II) basal levels by radioimmunoassay in 130 PCOS patients and 107 normal women. In addition, we observed the effect of GH on the outcome of ovulation induction in 7 poor responders to human menopausal gonadotropin (hMG) treatment. RESULTS: The mean serum GH level is (2.50 +/- 1.33) micrograms/L and (1.04 +/- 0.47) micrograms/L respectively in nonobese and obese PCOS patients which were significantly lower than those in controls [(5.30 +/- 2.26) micrograms/L, (2.95 +/- 1.49) micrograms/L respectively, P < 0.05]. The mean serum IGF-II level is (136 +/- 27) nmol/L in the obese PCOS patients, significantly greater than those in nonobese PCOS and controls (P < 0.05). When we used GH with hMG in 7 poor responders, the total amount of hMG required decreased from 1 to 12 amples and the duration of treatment shortened as compared with hMG alone. CONCLUSION: There is abnormal GH secretion in patients with PCOS, GH may improve the outcome of ovulation induction by gonadotropin. PMID- 11778544 TI - [Study on the correlation of estrogen receptor gene polymorphism to bone mineral density of radius in Chinese Han postmenopausal women in Beijing]. AB - OBJECTIVE: To investigate the distribution of estrogen receptor (ER) gene polymorphism in postmenopausal Han women in Beijing as well as its correlation with bone mineral density (BMD) of radius. METHODS: Xba I, and Pvu II polymorphism of ER gene were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 99 healthy postmenopausal Han women. BMD of distal (spongy bone) and proximal (compact bone) radius were determined by dual-energy X-ray absorptiometry (DEXA) as well. The relationship between BMD and polymorphism of ER gene was analyzed by variance analysis. RESULTS: Pvu II polymorphism of ER gene is not associated with BMD of both sites of radius (P > 0.05); while Xba I polymorphism of ER gene is significantly associated with BMD spongy and compact bone of radius (P < 0.05). Women with XX genotype have the lowest BMD T-score of -1.55 +/- 0.37 for the compact and -2.54 +/- 0.38 for the spongy, and those with xx genotype have the highest BMD T-score of -0.95 +/- 0.24 for compact and -1.74 +/- 0.16 for spongy. CONCLUSION: There is a significant correlation of Xba I polymorphism of ER gene with BMD of distal and proximal radius. It is indicated that the difference in ER genotypes among individuals might influence the development of osteoporosis. PMID- 11778545 TI - [Relationship between placenta growth factor and the pathogenesis of pregnancy induced hypertension syndrome]. AB - OBJECTIVE: To determine whether pregnancy induced hypertension syndrome (PIHs) is associated with placenta growth factor (PLGF). METHODS: PLGF level in the maternal and umbilical venous serum collected from 23 PIHs patients and 20 normotensive controls was measured by enzyme linked immunoassay (ELISA), and expression of PLGF and its mRNA in the placenta and decidua from them was assessed by the immuno-histochemistry and reverse transcriptional-polymerase chain reaction (RT-PCR). RESULTS: (1) PLGF levels in the maternal serum from PIHs [(112.7 +/- 63.8) micrograms/L] were significantly lower than those from normal pregnancies [(200.3 +/- 140.9) micrograms/L], (P < 0.05), and they were correlated with infant birth weight and placental mass (r = 0.4, r = 0.6). (2) Expression of PLGF in sycytiotrophoblast and villous mesenchyme and decidua from PIHs significantly decreased respectively (P < 0.01, P < 0.01, P < 0.05), and expression of PLGF in sycytiotrophoblast was associated with the severity of PIHs (P < 0.05). (3) The transcription of total PLGF mRNA in the placenta and decidua from PIHs decreased significantly (P < 0.05 and P < 0.05 respectively). Particularly, the transcription of PLGF-2 mRNA decreased significantly in the placenta from PIHs. CONCLUSION: The abnormal expression of PLGF may play an important role in the pathogenesis of placental ischaemia hypoxia in PIHs. PMID- 11778546 TI - [Expression of vascular endothelial growth factor in placenta from pregnancy complicated with pregnancy induced hypertension]. AB - OBJECTIVE: To study the expression of vascular endothelial growth factor (VEGF) in placenta from normal pregnancy and pregnancy complicated with pregnancy induced hypertension (PIH) and the effect of VEGF on the etiology of PIH. METHOD: Use the immunohistochemistry to determine the location and intensity of VEGF staining in placenta from 21 cases of normal pregnancy and 62 cases of mild, moderate and severe group of pregnancies complicated with PIH. RESULT: Immunolocalization of VEGF in all cases was observed mainly in syncytiotrophoblast. Intensity of VEGF immunostaining in syncytiotrophoblast was significantly reduced in the moderate PIH group (P < 0.05) and the severe PIH group (P < 0.01) compared with both the mild PIH group and the normal group, while there was no qualitative differences between the mild PIH group and the normal group. Intensity of staining in decidual cells was also similar in all the groups. CONCLUSION: These results suggest that VEGF is secreted mainly by syncytiotrophoblast in human placenta and the reduced VEGF may be responsible, at least in part, for the impaired vascular development in PIH. PMID- 11778547 TI - [Establishment of MRP-overexpression subline of bladder carcinoma and its MDR phenotype]. AB - OBJECTIVE: To investigate MRP expression and multidrug resistance(MDR) phenotype of a bladder carcinoma subline transfected with the full length MRP cDNA. METHODS: After transfection, a stable MRP-overexpressed subline named EJ/MRP was established. Gene expression of MRP and mdr1 were detected by using RT-PCR and immunohistochemistry methods. Drug sensitivity testing of the EJ/MRP cells to 11 kinds of anti-cancer agents was examined. RESULTS: Compared with EJ/Vect which was mock transfected, MRP mRNA level of EJ/MRP increased 14.3 fold and MRP expression was mainly located in cytosol and plasma membrane. The relative resistance (RR) to VP-16, vincristine increased more than 10 fold, and that to doxorubicin, hydroxycamptothecin, thiotepa, mitomycin and cyclophosphamide increased 3 to 10 fold. CONCLUSION: Bladder carcinoma with stably over-expressed MRP presents typical MDR phenotype but without mdr1/P-gp expression. It provides a good model and positive control for the study of MRP-mediated MDR. PMID- 11778549 TI - [The effects of RA538 and antisense c-myc on cervical cancer cell lines with high expression of bcl-2 gene]. AB - OBJECTIVE: To study the effects of recombinant adenovirus with RA538 or antisense c-myc insert on cervical cancer cell lines with high expression of bcl-2 gene. METHODS: Cervical cancer cell lines HeLa and SiHa were transduced with full length bcl-2 cDNA by lipofectin and cell clones with stable expression of bcl-2 were selected. They were then transfected with recombinant adenovirus containing RA538 (Ad-RA538), antisense c-myc (Ad-ASc-myc) or LacZ (Ad-LacZ) gene. Morphologic and molecular changes of the transfected cancer cells were examined by light microscopy, MTT, RT-PCR and Northern blot. RESULTS: The bcl-2 cDNA was successfully transferred into HeLa and SiHa cells. Two cell lines, called HeLa bcl2 and SiHa-bcl2 with high expression of bcl-2 gene were generated. Ad-RA538 and Ad-ASc-myc transfection both could inhibit cell growth and induce apoptosis of HeLa and SiHa cells, and inhibit their expression of c-myc and bcl-2 genes. However, although Ad-RA538 and Ad-ASc-myc had some inhibitory effect on bcl-2 and c-myc gene expression by HeLa-bcl2 and SiHa-bcl2 cells, they could only slightly inhibit cell growth and weakly induce apoptosis. CONCLUSION: Ad-RA538 and Ad-ASc myc can to certain extent inhibit cell growth and induce apoptosis of two cervical cancer cell lines. They have little such effect when these cell lines have over-expressed bcl-2 by transduction of exogenous bcl-2 gene. PMID- 11778548 TI - [Effect of IGF1 receptor gene antisense oligodeoxynucleotide on T24 urinary bladder cancer cells]. AB - OBJECTIVE: To evaluate the effects of autocrine blockage on T24 urinary bladder cancer cells. METHODS: Semiquantitative RT-PCR, MTT determination, 3H thymidine incorporation, flow cytometry and electron microscopy were used to study the effects of antisense oligodexynucleotide (ODN) targeted against insulin-like growth factor 1 receptor (IGF1R) gene on IGF1R gene expression, drug sensitivity, proliferation and apoptosis of T24 cells. RESULTS: After being treated with antisense ODN specific for IGF1R gene for 48 hours, the intrinsic IGF1R mRNA expression of T24 cells reduced approximately by 72.9%, which caused decrease in survival and increased sensitivity to mitomycin-induced apoptosis(P < 0.05). CONCLUSION: To block the autocrine loop with IGF1R antisense oligonucleotide may serve as a potential therapeutic approach to bladder cancer. PMID- 11778550 TI - [Effects of PML and PML-RAR alpha antisense oligonucleotides on promyelocytic leukemia cell line NB4]. AB - OBJECTIVE: To investigate the different effects of anti-PML (promyelocytic leukemia) and anti-PML/RAR alpha (promyelocytic leukemia/retionic acid receptor alpha) antisense oligonucleotides on cell growth, expression of PML-RAR alpha mRNA and PML-RAR alpha/PML protein location of NB4 cell line. METHODS: RT-PCR was used for PML-RAR alpha mRNA expression, trypan blue exclusion for cell count, methylcellulose assay for leukemic colony forming unit, immuno-fluorescence for PML-RAR alpha/PML protein localization. RESULTS: Both anti-PML start codon region antisense (STAS) and anti-PML-RAR alpha fusion region antisense (FUAS) could inhibit cell growth and formation AML-CFU. Cells became partially differentiated on day 5, being more marked in FUAS-treated cells than in STAS-treated ones. Down regulated PML-RAR alpha mRNA expression occurred at 24 h was in STAS and FUAS treated cells and maintained for up to 72 h. Immuno-fluorescence analysis with anti-PML monoclonal antibody showed a remarkable decrease to almost complete disappearance of microgranules. The residual granules became enlarged to become discrete dots (< 10 per cell), similar to normal POD structure in some STAS treated cells at 24 h. AT 72 h, nearly all the granules disappeared. Similar changes were observed in FUAS-treated cells. CONCLUSION: Both PML and PML-RAR alpha antisense oligonucleotides can specifically block the expression of PML-RAR alpha at mRNA and protein levels. PML protein is implicated in the regulation of cell differentiation. PMID- 11778551 TI - [Mechanism of enhanced invasiveness of human hepatocellular carcinoma by integrin alpha 6 beta 1]. AB - OBJECTIVE: To study the mechanism of enhanced invasiveness of human hepatocellular carcinoma (HCC) by laminin (LN) receptor integrin alpha 6 beta 1. METHODS: A stable transfectant of HCC Bel 7402 cell line, the alpha 6 beta 1 receptors of which were replaced by non-functional LN receptor alpha 6 beta 4-TR using dominant negative strategy, was used. Motility of the non-transfected, mock transfected and transfected tumor cells was assessed by the number of cells migrated to an area scratched out of cells on tumor cell monolayer. Tumor cell invasion was examined by cell penetration through a Matrigel layer in Boyden chamber. Matrix metalloproteinases (MMPs) secretion was detected by gelatin zymography. RESULTS: The migration of HCC Bel 7402 cells expressing dominant negative alpha 6 beta 1 was significantly decreased. Their invasive capability was decreased by 46.7%. The secretion of MMP-9 was almost totally inhibited and the activated MMP-2 was decreased by 43.9%. CONCLUSION: The decrease in cell motility, invasiveness and MMPs secretion of HCC cells expressing dominant negative alpha 6 beta 4 TR implies that LN-integrin interaction plays important role in HCC progression. PMID- 11778552 TI - [Mutation of human O6-alkylguanine-DNA alkyltransferase confers resistance to O6 benzylguanine]. AB - OBJECTIVE: O6-alkylguanine-DNA alkyltransferase (O6-AGT), capable of repairing DNA damage, is responsible for tumor cell resistance to nitrosourea. While O6 benzylguanine as a selective inhibitor of AGT helps reverse drug resistance, it would aggravate myelo-suppression. This investigation is to generate AGT mutant and see if it would confer resistance to O6-benzylguanine-induced inhibition but leave its alkyltransferase activity intact. METHODS: Human O6-methylguanine-DNA methyltransferase (MGMT) cDNA was mutated by site-directed mutagenesis. The mutant cDNA was transferred into E. coli and the protein expressed was purified. The activity of the mutant MGMT was determined in vitro with O6-(3H) methylguanine-DNA as substrate. RESULTS: Two mutant MGMT proteins were obtained: G156A and P140A, with glycine-to-alanine mutation at position 156 and proline-to alanine mutation at position 140, respectively. The AGT activity of both mutants was similar to that of the wild type MGMT. However, their resistance to O6 benzylguanine was significantly increased up to 105.8 and 13.5 fold, respectively as compared to that of the wild type MGMT. CONCLUSION: The results suggested that transduction of the mutant MGMT herein reported into hematopoietic progenitor cells may lead to their selective resistance to the combined use of O6 benzylguanine and alkylating agents designed to overcome tumor resistance to nitrosourea treatment. PMID- 11778553 TI - [Clinical implication of apoptosis of breast cancer induced by preoperative chemotherapy]. AB - OBJECTIVE: To investigate whether apoptosis could be induced by preoperative chemotherapy in breast cancer patients, and determine if it is correlated with clinical response and patients' survival. METHODS: Apoptosis was assayed by in situ DNA end labeling and receptors for estrogen and progesterone were examined immunohistochemically. Comparison of the differences in apoptotic index (AI) and clinical response was made between patients received preoperative chemotherapy and those did not, using the one tailed Student's t-test. The Kaplan-Meier method was utilized to calculate relapse-free and overall survival time. Cox proportional hazards model was used to conduct multivariate analysis of prognostic factors and differences in overall survival and relapse-free survival after adjustment for other variables. RESULTS: Apoptosis was induced by preoperative chemotherapy, especially in lymph node positive patients. Post chemotherapy AI correlated with better clinical response and increased patient survival, including relapse (disease) free survival and overall survival. CONCLUSION: The extent of apoptosis induced by preoperative chemotherapy of primary breast cancer may possibly predict an individual patient's overall response to treatment. PMID- 11778554 TI - [Evaluation of several biological markers in the prognosis of patients with node negative breast cancer]. AB - OBJECTIVE: To evaluate the practical significance of microvessel count (MVC), c erbB-2, CD44, cathepsin D and nm23 expression, and clinico-pathological parameters in the prognosis of node-negative breast cancer. METHODS: Sixty two patients with node-negative invasive breast cancer were treated by surgery alone, and followed-up for at least 10 years. Microvessel count (MVC), C-erbB-2, CD44, Cathepsin D and nm23 expression were studied by immunohistochemical technique. With other clinico-pathological parameters, they were evaluated prognostically. RESULTS: Univariate analysis showed that the prognostic factors influencing 10 year overall survival rate were MVC, C-erbB-2, stromal cell cath-D and CD44 expression. Multivariate analysis demonstrated that MVC was the sole independent prognostic factor determining 10-year survival. CONCLUSION: Although MVC, c-erbB 2, stromal cell cath-D and CD44 expression are all of prognostic significance, MVC is most meaningful in evaluating prognosis of node-negative breast cancer patients. PMID- 11778555 TI - [Nitric oxide synthase and vascular endothelial growth factor expression in hepatocellular carcinoma and their relation to angiogenesis]. AB - OBJECTIVE: To analyse inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) protein expression in hepatocellular carcinoma (HCC) and their relation to angiogenesis. METHODS: Tissue sections from 71 HCC patients were examined immunohistochemically for protein expression of iNOS, eNOS, and VEGF. Microvessal density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. RESULTS: Positive iNOS and eNOS immunostaining was detected in 83.1% and 85.9% of HCC respectively. iNOS and eNOS were not detected in normal hepatic tissue. MVD was 34.3 +/- 1.5/HP and 38.6 +/- 1.6/HP in HCC positive for iNOS and VEGF while it was 31.2 +/- 2.8/HP, and 22.4 +/- 2.0/HP in HCC negative for iNOS and VEGF respectively (P < 0.01). A correlation between NOS expression and VEGF in HCC was not observed. CONCLUSION: iNOS and eNOS may play a role in malignant transformation of post-hepatic cirrhosis. The expression of iNOS and VEGF favors angiogenesis of HCC. PMID- 11778556 TI - [Expression of LRP, MRP and MDR1 in non-small-cell lung cancer and its clinical significance]. AB - OBJECTIVE: To detect expression of lung resistance protein (LRP), multidrug resistance-associated protein(MRP) and multidrug resistance 1(MDR1) mRNA, and its clinical significance in non-small-cell lung cancer (NSCLC). METHODS: RT-PCR was used to investigate mRNA expression of the above mentioned genes. RESULTS: The frequency of expression of LRP, MRP and MDR1 was 74.2%, 80.3% and 37.9%, respectively. A significant positive correlation was observed between LRP and MRP(r = 0.47, P = 0.001), but this association was found neither between LRP and MDR1, nor between MRP and MDR1. The expression of LRP, MRP and MDR1 did not vary with the grade of cell differentiation and TNM staging. In adenocarcinomas which responded to chemotherapy, there was lowered expression of both LRP and MRP than those which did not respond. In chemo-responsive squamous-cell carcinomas, however, this was true of LRP expression only. The median survival time of NSCLC patients with co-expressed 2 and 3 drug resistance related genes was significantly reduced. CONCLUSION: The intrinsic multidrug resistance of NSCLC involves the combined effects of LRP, MRP and MDR1. PMID- 11778557 TI - [APC gene expression in precancerous lesions of stomach examined by light and electron microscopic in situ hybridization]. AB - OBJECTIVE: To study the significance of abnormal expression of APC gene in gastric cancer and its precancerous lesions. METHODS: The expression of APC gene was examined in 119 cases of precancerous lesions and 40 cases of gastric cancers by light and electron microscopic in situ hybridization technique. RESULTS: 1. The positive rate of APC gene expression in normal gastric mucosa, mild dysplasia, moderately severe dysplasia, severe dysplasia and gastric cancer was 83.3%, 77.8%, 62.5%, 25.9%, and 6.7%-8.0%, respectively. 2. In 4 types of intestinal metaplasia (IM), APC gene expressed much more frequently in colonic type than in small intestinal type (P < 0.05), more frequently in incomplete type of IM than in complete type (P > 0.05). The positive rate of incomplete colonic type was the highest. 3. Under electron microscope, the APC positive signals were located in the cytoplasm matrix of gastric mucosa cells. They decreased gradually from normal parietal cells, dysplasia cells to cancer cells till negative. CONCLUSION: Abnormal expression of APC gene occurs mainly in precancerous lesion severe dysplasia. It is considered as an early event during gastric carcinogenesis. Detecting APC gene in gastric mucosa helps predict the trend of dyplasia to become malignant, and diagnose gastric cancer in early stage. PMID- 11778558 TI - [Evaluation of ten-year results of cancer prevention and treatment in Changle City with high incidence of gastric cancer]. AB - OBJECTIVE: To evaluate the results of cancer prevention and treatment over a 10 year period (1988-1997) in Changle City with high incidence of gastric cancer. METHODS: The results were analysed with sick rate random test, trend test, GM and Kaplan-Meier method with SAS statistical software. RESULTS: During the ten years, the sick rate of malignant tumors in male residents initially increased but then decreased. Gastric cancer had a tendency to decline. There was no obvious change for females. By short-term prediction, the sick rate of malignant tumors and gastric cancer would decrease, and that of liver cancer remain steady. The life expectancy of male residents increased 4.2 years and that of female residents increased 1.8 years from 1988 to 1997 if cancer death was ignored, but the increase was not significant if only deaths from gastric and liver cancers were excluded. The 5-year survival rate of gastric cancer and liver cancer increased 8.8% and 29.3% from 1988 to 1990, respectively. The cumulative risk rate of gastric cancer in males was 3 times as high as that of females, and that of liver cancer in males was 2.5 times as high as that of females. CONCLUSION: Sustained measures of cancer prevention and treatment woult anticipate further improvement of health status of Changle's residents in the years to come. PMID- 11778559 TI - [Appraisal of postoperative transcatheter arterial chemoembolization (TACE) for prevention and treatment of hepatocellular carcinoma recurrence]. AB - OBJECTIVE: To evaluate the effect of postoperative TACE for prevention and treatment of hepatocellular carcinoma (HCC) recurrence after radical resection. METHODS: From Jan. 1995 through March 1998, 109 HCC patients after radical resection were followed up with serum AFP, liver US and CT, chest X-ray film, hepatic artery angiography, etc. They were divided into 2 groups. Patients in group A (n = 68) with no residual tumor were given prophylactic TACE treatment, 1 2 times at the second and fifth month after operation. Patients in group B (n = 41) with residual tumor left were treated with regular TACE, once every 2 months. The 2 groups of patients were followed up for 6-45 months after operation. RESULTS: In group A, the real curative resection rate was 62.4%. Tumor recurrence was found in 10 of the 68 patients, with a total recurrence rate of 14.7% within 3 years after radical resection. The 1-, 2-, and 3-year cumulative recurrence rate was 7.4%, 13.2% and 14.7%, respectively. The 1-, 2-, and 3-year survival rate was 100%, 93.4% and 85.7%, respectively, while that in group B was 78.1%, 57.7% and 57.7%, respectively. The differences between the 2 groups of patients were statistically significant. The predictive pathological factors hampering completeness of tumor resection were: tumor size > 5 cm, more than 2 tumor nodules, the presence of satellite nodules, tumor with partial or without encapsulation and tumor thrombus in portal vein. Hepatic artery angiography with LP-CT and maintenance of high serum AFP level were the most sensitive methods for detecting residual tumor after operation. CONCLUSION: Post-operative TACE is very useful for prevention and treatment of HCC recurrence. It helps improve survival of surgically treated HCC patients. PMID- 11778560 TI - [Imaging findings of intrahepatic peripheral cholangiocarcinoma]. AB - OBJECTIVE: To study the imaging features of intrahepatic peripheral cholangiocarcinoma. METHODS: The imaging features of 11 cases of surgically and pathologically confirmed intrahepatic peripheral cholangiocarcinoma were retrospectively reviewed. B-ultrasonic scanning(BUS) was performed in all patients. CT was done in 8 patients, including conventional unenhanced scanning followed by enhanced scanning in 4 patients, dynamic double-stage scanning in 2 patients, and dynamic double-stage scanning followed by delayed scanning in the other 2 patients. Of the 3 patients received MRI, conventional SE series, T1WI and T2WI were performed in 2 patients, conventional SE series and dynamic scanning in the other one. RESULTS: All lesions were hypo-echoic in BUS, homogeneous or heterogeneous. On unenhanced CT, the lesions were of low density with ill-defined border. On enhanced scanning, moderate enhancement was observed at the edge of the lesions. MRI was of low intensity in T1WI and moderately high intensity in T2WI. Dynamic MRI and double-stage CT scanning showed characteristic enhancement from the periphery toward the center of the lesion. Focal dilatation of the intrahepatic bile ducts around the tumor was seen in 6 cases and retraction of liver capsule in 3 cases. CONCLUSION: To some extent, the imaging features of intrahepatic peripheral cholangiocarcinoma are characteristic. They are useful for differentiating these tumors from other space-occupying lesions in the liver. PMID- 11778561 TI - [Management of the neck for patients with thyroid papillary carcinoma]. AB - OBJECTIVE: To search an optimal management of the neck for patients with thyroid papillary carcinoma. METHODS: Clinical data of 424 cases with thyroid papillary carcinoma treated in our hospital from Jan, 1965 to Jan, 1987 were analyzed retrospectively. Patients with positive cervical lymph nodes (N+) were treated with radical excision of the primary tumor and neck dissection. For patients without cervical lymph node involvement (N0), neck dissection was spared. On follow-up, whenever cervical lymphatic node metastasis occurred, neck dissection was performed. All patients were followed up for more than 10 years. RESULTS: The 5- and 10-year survival rate of the 258 N+ patients was 84.3% and 80.4% respectively, and that of the 166 N0 patients was 94.1% and 91.3% respectively. Twenty-three N0 cases later developed cervical lymph node metastasis. Their 5- and 10-year survival rate was 91.4% and 82.2% respectively after neck dissection. CONCLUSION: Since only 13.9% of N0 thyroid papillary carcinoma patients who did not receive neck dissection develop cervical lymph node metastases later, and their survival rate was just as good where neck dissection is postponed until metastases occur, prophylactic neck dissection seems unnecessary. PMID- 11778562 TI - [Childhood thyroid carcinoma: an analysis of 14 cases]. AB - OBJECTIVE: To reveal the clinical characteristics, causes of misdiagnosis, treatment and prognosis of thyroid carcinoma in children. METHODS: Fourteen patients under 14 years of age with thyroid carcinoma were retrospectively reviewed. RESULTS: According to UICC's clinical and histopathologic classification (1989), there were 12 cases of papillary carcinomas (83.3%), 2 cases of follicular carcinomas (16.7%). All but one case were in stage I. Cervical lymph node metastasis was found in 12 cases (85.7%). Diagnosis was incorrect in 7 cases. All patients were operated, including unilateral neck dissection in 11 and bilateral neck dissection in 2. One patient received palliative subthyroidectomy and postoperative 131I treatment. In the follow-up period of 2 to 13 years (mean 6 years), no patient died. CONCLUSION: Thyroid cancer in children are mostly papillary carcinomas with good prognosis, regardless of high frequency of cervical lymph node metastases. Early cases can be picked up if misdiagnosis be avoided. PMID- 11778563 TI - [Preoperative chemotherapy and operation for invasive Masaoke stage III and IV a thymoma]. AB - OBJECTIVE: To assess the effect of preoperative chemotherapy on invasive thymoma. METHODS: Fourteen patients with invasive thymoma (12 cases in Masaoka stage III and 2 cases in stage IV a) were treated with 3-4 cycles of CAVP (cyclophosphamide 600 mg/m2 D1, adriamycin 30 mg/m2 or epi-adriamycin 40 mg/m2 D1, vincristine 0.6 mg/m2 D1 or vindestine 3 mg/m2 D1, D8, cisplatin 30 mg/m2 D1, 2, 3). Following chemotherapy, patients were operated within 1-3 months. In 10 patients, sternotomy was performed and in 4 patients, anterolateral thoracotomy was performed. Radiotherapy was given with a total dose of 50-60 Gy in all patients except in those who were pathologically in complete remission. The patients were followed up for 6 months to 3 years. RESULTS: After chemotherapy, complete response was observed in 5 patients (35.7%) and partial response in 9 patients (64.3%). Nine patients received radical tumor resection and 5 patients received partial resection. Histologic/examination of the surgical specimens showed fibrosis of the remnant thymus in 5 patients. All but two patients survived in the follow-up period. Patient died from distant metastases at 18 and 24 months after treatment, respectively. CONCLUSION: Preoperative chemotherapy helps increase the resectability of stage III and IV a invasive thymoma. A longer follow-up period and more patients are needed to ascertain the impact of this treatment strategy on long-term survival. PMID- 11778564 TI - [Ifosfamide combination chemotherapy for advanced gynecologic malignancies]. AB - OBJECTIVE: To evaluate the clinical efficacy and toxicity of ifosfamide (IFO) combination chemotherapy in patients with advanced gynecologic malignancies. METHODS: Thirty-four patients with gynecologic malignancies were included in this series. Of the 34 patients, 26 with epithelial cancer of the ovary were previously treated with cisplatin-containing combination chemotherapy but failed to respond or recurred after treatment. They were treated with IEP (IFO, VP16, PDD) regimen. The remaining 8 patients with uterine sarcoma (5 cases), squamous cell carcinoma of the uterine cervix with metastases to the liver or bone (2 cases), and endometrial carcinoma with lung metastases (1 case) were treated with IFO combination chemotherapy. At least two courses of treatment were given unless tumor progression occurred after the first course. RESULTS: The overall response rate was 35.3% including 8.8% complete response. The response rate of 26 patients with ovarian cancer was 30.8%. Two patients with PDD-sensitive tumor all achieved complete response, which lasted for one year. The response rate of the remaining 24 PDD-resistant patients was 25% with a mean duration of 5.5 months. There was no complete response. Two patients with cervical carcinoma and two of five patients with uterine sarcoma responded to IFO combination chemotherapy. Relatively severe hematological toxicity was observed, including grade III and IV leucopoenia and thrombocytopenia. Two patients died from severe toxicity. CONCLUSION: IFO combination chemotherapy is effective in treating recurrent or progressive gynecologic malignancies, especially PDD-sensitive ones. Myelosuppression is relatively severe which may be due to prior long term and intensive chemotherapy. PMID- 11778565 TI - [Treatment of advanced Hodgkin's disease: an analysis of 128 cases]. AB - OBJECTIVE: To explore the rational treatment for advanced Hodgkin's disease. METHODS: A total of 128 patients with advanced Hodgkin's disease was included in this study. They could be divided into 3 groups according to the treatment they received. Patients in group 1 (n = 99) were treated by combination chemotherapy plus radiotherapy. Patients in group 2 (n = 24) were treated by chemotherapy alone. The remaining 5 patients in group 3 were treated by radiotherapy alone. The chemotherapeutic regimens used were MOPP, MOPP alternating with CHOP, or with ABVD. RESULTS: The overall response rate of 127 evaluable patients was 96.1%. The overall 1-, 3-, 5, and 10-year survival rate was 91.4%, 70.3%, 56.8% and 52.4%, respectively. The complete response (CR) rate in the 3 groups of patients was 69.7%, 58.3% and 100%, respectively. Patients in clinical stage III with no bulky mass, no systemic symptoms, and their tumor was predominantly of lymphocytic or nodular sclerotic type had better long term survival than those in clinical stage IV with bulky mass, systemic symptoms, and with lymphocyte depleting, mixed cellular tumor. Better long term survival was seen in patients who showed complete response to combined chemotherapy and radiotherapy. At least 6 cycles of chemotherapy were needed. CONCLUSION: Combination chemotherapy plus radiotherapy is effective in the treatment of advanced Hodgkin's disease. PMID- 11778566 TI - [Clinical study of prophylactic cranial irradiation for small-cell lung cancer]. AB - OBJECTIVE: To study the influence of prophylactic cranial irradiation (PCI) on survival and brain metastases in patients with limited small-cell lung cancer (SCLC). METHODS: Fiftyone patients with limited SCLC under complete remission after chemoradiotherapy were randomly divided into prophylactic cranial irradiation (PCI) group (n = 26) and control group (n = 25). Patients in PCI group received irradiation at a dose of 25.2-30.6 Gy. Survival rates were analyzed and compared by life table and Long-Rank, incidence of cranial metastases by chi 2 test. RESULTS: The clinical features of patients such as age, sex, effect of treatment before PCI were similar between the two groups. The incidence of cranial metastases was 3.8% in PCI group in contrast to 28% in the control group (P < 0.05). The 1, 2, 3-year survival rate was 84.6%, 73.1%, 42.3% respectively in PCI group and 72%, 40%, 32% respectively in the control group. The differences between the two groups of petients were statistically insignificant. No serious sequela was observed in patients receiving PCI. CONCLUSION: PCI decreases the incidence of cranial metastases for patients with limited SCLC following complete response to chemoradiotherapy, but it does not improve survival. PMID- 11778567 TI - Is this the next Cipro? Not quite. PMID- 11778568 TI - In defense of denial. PMID- 11778569 TI - Sleepless in America. PMID- 11778570 TI - Too big for their niches. PMID- 11778571 TI - Memory and motor skill components of the WAIS-III Digit Symbol-Coding subtest. AB - We examined motor skill and memory components of the Digit Symbol-Coding subtest of the WAIS-III in a clinical sample. Research using previous versions of the WAIS in non-clinical samples has suggested that the age-related decline in Digit Symbol-Coding scores is more related to motor ability rather than to the memory requirements of the test. Our results extend this conclusion to a clinical sample, using the WAIS-II. Copy scores measure motor skill on the Digit Symbol Coding subtest, and Incidental Learning scores (Free Recall and Pairing) measure memory. A large proportion of Digit Symbol-Coding variance was explained by Copy scores with Incidental Learning scores controlled, but Incidental Learning scores explained little additional variance when Copy scores were controlled. The same pattern was found when we used the Immediate Memory and General Memory Indexes from the Wechsler Memory Scale-II as independent measures of memory. PMID- 11778572 TI - Understanding the diagnostic capabilities of cognitive tests. AB - Statistics (i.e., sensitivity, specificity, hit rates, positive and negative predictive values, odds ratios, and likelihood ratios) that best describe a diagnostic test's ability to classify persons as either "impaired" or "normal," but that are not commonly reported in neuropsychological research, are reviewed. These statistics are applied to Mayo Cognitive Factor Scale scores (MCFS; Smith et al., 1994) to demonstrate information that can be acquired about the diagnostic capabilities of cognitive tests as they are commonly used in clinical settings. Multivariate analyses then generated a statistical model that combines MCFS scores and improves on the diagnostic capabilities of the individual MCFS scores. This model enjoys better diagnostic power than individual scores. It establishes that cognitive testing that uses multiple measures is very good at differentiating normal from impaired cognitive states. Information is also provided that helps clinicians quantify a person's risk for cognitive impairment based on specific cognitive test score(s). PMID- 11778574 TI - Application of a short form of the Category Test for individuals with a traumatic brain injury: a cautionary note. AB - The Category Test, notable for its length, has been the subject of many proposed short-form versions. In our present managed care era, the pressure to utilize short forms of various tests with clinical populations has increased, yet the appropriateness of using short forms with various populations must be demonstrated not assumed. The present study examined the appropriateness of applying the short form of the Category Test proposed by Charter and colleagues (1997) with a sample of 100 outpatients with traumatic brain injuries referred for neuropsychological testing. Both variance accounted for by the short-form Category Test and the residuals or errors of prediction resulting from the use of the short-form Category Test were examined. While the short form of the Category Test accounted for 93% of the variance of full-form Category Test scores, examination of residuals indicated clinically significant (approximately 10 points or greater) estimation errors for 25% of the subjects. In light of the clinical significance of such extreme estimation errors, it was not recommended that this short form of the Category Test be used for individuals with a traumatic brain injury. PMID- 11778573 TI - Effects of practice on category fluency in Alzheimer's disease. AB - Evaluation of patients with suspected Alzheimer's disease (AD) often involves clinicians of multiple disciplines working in collaboration to maximize diagnostic accuracy. Accordingly, repeated administrations of some common tests of mental status may occur within a relatively brief time period. The effect of such retesting on subsequent results is largely unknown for many cognitive tasks, despite the possibility that repeated administrations may artificially inflate scores. To assess the potential impact of practice effects on a commonly administered verbal fluency task, animal naming was administered twice within a 1 week period to 111 patients with probable AD and 12 persons without dementia. Non demended subjects were the only group to demonstrate a small (3 point), but statistically significant practice effect. Regardless of level of cognitive impairment, patients with AD did not show significant practice effects over repeated administrations of animal naming after a relatively brief test-retest interval, suggesting the robust nature of this task in AD. PMID- 11778575 TI - Application of the multilingual aphasia examination-spanish in the evaluation of Hispanic patients post closed-head trauma. AB - Despite the rapid increase of Hispanics in the U.S., there continues to be a lack of adequate psychological assessment tools to examine Spanish-speaking patients with cognitive or neuropsychological disturbances. We investigated the clinical utility of the Multilingual Aphasia Examination-Spanish (MAE-S) in the evaluation of language functions of Hispanic subjects post-traumatic brain injury (TBI). The performance of 40 TBI patients was compared to that of 40 age-, gender-, and education-matched normal controls. Subject groups differed on the Visual Naming (VN), Controlled Oral Word Association (COWA), and Token Test subtests. The VN and COWA subtests were the best discriminators of group membership. Distribution of scores for the patient group on the Rating of Articulation scale additionally indicate subtle articulatory difficulties post-TBI. For all subtests, trauma severity per Glasgow Coma Scale was the best predictor of language performance, over and above the contribution of other clinical and demographic variables. These results are consistent with prior reports of dysphasia post-TBI and suggest that the MAE-S is a sensitive and accurate measure to assess language disturbances in Hispanic populations. PMID- 11778576 TI - Symptom validity testing: a critical review. AB - This paper provides a comprehensive review of the published literature on symptom validity tests (SVT) and, with the accompanying tables, serves as a reference to assist in their selection, interpretation, and defense. Because malingering is inherently an applied problem that frequently arises in a medico-legal context, the use of SVTs must meet certain standards. Thus, a number of methodological and theoretical weaknesses of SVT research which limit the use of SVTs as clinical tools and sources of evidence are highlighted. These criticisms incorporate recommendations which must be addressed if conclusions based on SVT data are to meet the increasingly rigorous standards for the admissibility of scientific evidence. PMID- 11778577 TI - Research in clinical neuropsychology with Hispanic American participants: a review. AB - Research on the neuropsychological assessment of adult Hispanic Americans has used mostly elderly, poorly educated, Spanish-speaking participants, resident in the United States for more than 15 years. Studies have involved comparisons with Anglo-Americans, the effects of moderator variables (e.g., bilingualism) and test standardization and validation. Most neuropsychological studies comparing Hispanic and Anglo-Americans have methodological weaknesses, such as overly liberal Type I error rates and inappropriate statistical controls for educational differences. What intergroup discrepancies do exist are likely due to educational (quantitative and qualitative) differences, non-equivalent Spanish/English translations and/or acculturation/ bilingualism related factors. Research suggests that Spanish-language neuropsychological test battery norms should be stratified by age, education (including lower grade levels), and to a limited extent gender, but there is little data to support separation by ethnicity. Acculturation/bilingualism variables can suggest when English-language tests are more appropriate to use with Hispanic Americans. PMID- 11778578 TI - New procedures to assess executive functions in preschool children. AB - Executive functions are difficult to assess in preschool children, yet the preschool period is particularly important, both in the development of behavioral control and of the brain, particularly the prefrontal cortex. Several tasks were adapted from developmental and neuroscience literature and then administered to 98 preschool children (30-, 36-, 42-, 48- and 60-month age groups). Executive function task performance was related largely to age group, but not to sex or intelligence. These tasks, then, were sensitive in this age range and may be useful to delineate distinct cognitive profiles among preschool children with various neurological and developmental disorders. PMID- 11778579 TI - Post-Traumatic amnesia: consistency-of-recovery and duration-to-recovery following traumatic brain impairment. AB - The aim of this research was to examine the nature and order of recovery of orientation and memory functioning during Post-Traumatic Amnesia (PTA) in relation to injury severity and PTA duration. The Westmead PTA Scale was used across consecutive testing days to assess the recovery of orientation and memory during PTA in 113 patients. Two new indices were examined: a Consistency-of Recovery and a Duration-to-Recovery index. A predictable order of recovery was observed during PTA: orientation-to-person recovered sooner and more consistently than the following cluster; orientation-to-time, orientation-to-place, and the ability to remember a face and name. However, the type of memory functioning required for the recall face and name task recovered more consistently than that required for memorizing three pictures. An important overall finding was that the "order-of-recovery" of orientation and memory functioning was dependent upon both the elapsed days since injury, and the consistency of recovery. The newly developed indices were shown to be a valuable means of accounting for differences between groups in the elapsed days to recovery of orientation and memory. These indices also clearly increase the clinical utility of the Westmead PTA Scale and supply an objective means of charting (and potentially predicting) patients' recovery on the different components of orientation and memory throughout their period of hospitalization. PMID- 11778580 TI - Factorial invariance for combined Wechsler Adult Intelligence Scale-Revised and Wechsler Memory Scale-Revised scores in a sample of clients with alcohol dependency. AB - This study examined the joint factor structure of the WAIS-R and WMS-R in a sample of 289 participants (mostly males) with alcohol dependency. In a confirmatory phase we contrasted a range of factor models derived from previous analyses of the Wechsler scales. The best fitting model incorporated five factors representing Verbal Comprehension, Perceptual Organization, Attention Concentration, Verbal Memory, and Visual Memory, with reassignment of factor loadings for two subtests. The invariance of the measurement model was then examined comparing data from a large sample of healthy participants (J. R. Carstairs & E. A. Shores, 1999). The results indicated that the number of factors was invariant across samples, and four of the factors satisfied the criterion of partial measurement invariance. PMID- 11778581 TI - Assessment and development of organizational ability: the Rey Complex Figure Organizational Strategy Score (RCF-OSS). AB - The Rey Complex Figure Organizational Strategy Score (RCF-OSS) was devised for pediatric populations to cater for developmental variability. A sample consisting of 376 children aged between 7.0 and 13.11 years was recruited for the standardization of RCF-OSS. The interrater reliability (.85 to .92) and temporal stability (.79 to .94) of the RCF-OSS are acceptable. RCF-OSS correlated moderately with RCF accuracy, memory and organization, however it seems to be measuring an independent aspect of performance, possibly strategy. Moderate linear relationships were observed with executive function and memory measures. Considerable age-related variation in strategy formation was observed with significant maturity occurring between the ages of 7 years and 11 years. Surprisingly, older children used fragmented strategies more than the younger age groups. In conclusion, the RCF-OSS is a useful adjunct to traditional accuracy scoring procedures, and the normative data indicates that organizational skills may not consolidate until middle to late adolescence. PMID- 11778582 TI - Connecticut Pictorial Learning Test: a pictorial version of the California Verbal Learning Test. AB - This paper describes the development of a pictorial version of the California Verbal Learning Test. The new instrument, named the Connecticut Pictorial Learning Test (COPLT), was tested in two experiments. The first experiment involved selection and testing of new verbal stimuli to be adapted for pictorial use. Results suggest that these new items are approximately equivalent in difficulty to the original CVLT stimuli. These stimuli can serve as CVLT alternate Form III for use in clinical verbal memory research. Recall means and standard deviations are provided for the new stimulus set with a young adult sample. The second experiment explores the psychometric properties of the new COPLT after stimuli were translated into pictorial form. The psychometric evidence suggests that the pictorial test has good internal consistency and concurrent validity with widely-used clinical memory tests. Furthermore, verbally mediated information processing serves successful pictorial learning and subsequent recall performance in normal healthy control subjects when verbally encodable pictorial stimuli are used. The use of semantic organization appears to be even more important for optimal performance using pictorial stimuli than with verbal stimuli. Scoring rules for the COPLT are included in the Appendix. PMID- 11778583 TI - HIPAA groups offer hospitals vehicles to share information, resources. PMID- 11778584 TI - [Tooth loss, dental restorations and dental attendance in Switzerland]. AB - The aim of this study is to report about the dental health situation in Switzerland and to evaluate frequencies of dental visits. Data were obtained from the first and second national Health Survey of the Federal Office for Statistics in 1992/3 and 1997. Based on a random sample of the population aged from 15 to 74 years, 71% participated in an oral interviews and of this group of individuals, 75% later filled in a written questionnaire in 1992/3. Data analysis showed that the proportion of the fully dentate population (28 remaining teeth) is 41%, while almost 50% had some prosthetic treatment. 31% were treated with fixed prostheses, i.e.crowns and/or bridges, and 19% with removable prostheses, i.e. partial and/or full dentures. With increasing age the number of missing teeth and the frequency of prosthetic treatment went up. The population with prosthodontic reconstruction increased mainly in the third and forth decades. In the elderly population (age 65-74 years), a shift was observed from fixed to removable prostheses; two thirds in this groups was restored with removable prostheses. The proportion of subjects visiting the dentist was by 70% in 1992/3 and declined to 65% in 1997. Subjects wearing removable prostheses had apparently lower frequencies (43%) in dental visits than subjects with fixed prostheses (80%). A potential concern exists for the edentulous population who presented a limited need for dental visits of only 22% during the year preceding the study. PMID- 11778588 TI - Monitoring clinical trials. Interim data should not be publicly available. PMID- 11778589 TI - Monitoring clinical trials. Caution may be warranted in releasing interim trial data. PMID- 11778590 TI - Monitoring clinical trials. Several points are contentious. PMID- 11778591 TI - Monitoring clinical trials. Interim data are at least as important as interim analyses. PMID- 11778592 TI - Monitoring clinical trials. Latest data from START trial should be made available. PMID- 11778593 TI - Getting consent for necropsies. Most relatives give consent once reasons for necropsy are explained. PMID- 11778594 TI - Getting consent for necropsies. Bereavement teams might ask for consent for necropsy. PMID- 11778595 TI - Quality of care for people with dementia. Dementia care mapping is inadequate tool for research. PMID- 11778596 TI - Quality of care for people with dementia. Registries charting epidemiological trends and benchmark outcomes are required. PMID- 11778597 TI - National service frameworks. National service framework for older people is worth a try. PMID- 11778598 TI - Selected bibliography. PMID- 11778599 TI - Making a difference. PMID- 11778601 TI - What's it like to be a fellow? PMID- 11778602 TI - Nursing--one strong voice? PMID- 11778600 TI - Planning for the future--the integration of genetics into cancer care. PMID- 11778603 TI - American Academy of Nursing call for applications Scholar-in-Residence programs. PMID- 11778604 TI - Technical efficiency of nursing units in a tertiary care hospital in Taiwan. AB - The variation in productivity and cost efficiency has been observed among 57 nursing units in a large tertiary care hospital. The inefficient units can achieve the same level of efficiency as the efficient units by altering their inputs (either nursing hours or patient costs). The optimization can be achieved through proper reallocations of nursing resources such as nursing hours or costs. However, the resource reallocation to achieve high efficiency should not be at the expense of quality of care. Future efficiency studies should incorporate the nursing sensitive measures of quality in the analysis. PMID- 11778606 TI - Current state of ergonomics in agriculture--future needs. VIII International Symposium on Ergonomics, Work Safety and Occupational Hygiene. 22-24 October 2001, Lublin. PMID- 11778607 TI - [On the studies of the problem of X-ray units conducted from 1929 to 1937: centering on the studies in American and British radiological societies]. AB - The problem of the units of X-ray exposure originated from the fact that therapists wished to grasp the relationship between the quantity of irradiated X ray and its effect on medical treatment, and to make a comparative study of each therapeutic result by the same measure. This problem was an interdisciplinary one between physics and radiotherapeutics. In 1925, the Radiological Society of North America settled the Committee on Standardization of X-ray Measurements to study the problem of measuring X-rays, and to guide the members of the Society. The committee was composes of physicists and radiologists in equal number. They developed a large-sized standard chamber and a portable one. L. S. Taylor transported the portable chamber to Europe and by using it he compared and examined British, German and French standard chambers, confirming that each of them could be used as a common standard chamber. Based on these facts the ICRU presented the Annex to the recommendations of 1934 on the standard measuring apparatus. It was shown by physicists that the effect on the human body was not represented only by the quantity of irradiated X-rays and that a description of the quality of X-rays was indispensable. As radiologists' understanding deepened, they came to actively submit proposals to radiological societies in the 1930's. Taking their opinions into consideration, the ICRU recommendations which were practicable for medical purposes were issued in 1937. The effort of American and British radiological societies for a better solution beyond disciplines is suggestive in dealing with interdisciplinary issues. PMID- 11778605 TI - Fever and neutropenia in children with solid tumors is similar in severity and outcome to that in children with leukemia. AB - There is growing interest in developing criteria that will allow efficient prospective discrimination between cancer patients at high and at low risk for complex fever and neutropenia. The objective of this study was to determine whether there were differences in patterns of documented infections and outcome of episodes of fever and neutropenia in pediatric patients with leukemia and those with solid tumors, a potential risk factor. A total of 283 febrile neutropenia episodes in pediatric cancer patients at a single center were retrospectively reviewed; 38% of the patients concerned had leukemia and 62% had solid tumors. Fever of unexplained origin was seen in 73% and 74% of episodes in patients with leukemia and solid tumor, respectively. Bacteremia occurred in 18% and 16% of patients in these respective groups. There was no difference in the type of microorganisms that were isolated in the groups, with gram positives predominating in both. The median duration of fever was 2 days in both groups. The depth of neutropenia was similar, with 75% of leukemia patients and 70% of solid tumor patients presenting with ANC of 100 cells/microl or lower. The median duration of neutropenia was 9 days in patients with leukemia and 6 days in solid tumor patients. The median duration of antibiotic treatment was 9 days and 7.5 days in the same respective groups. Antibiotic modification occurred in 25% episodes of febrile neutropenia in leukemia patients and in 11% of episodes in solid tumor patients. No deaths occurred in either group. Subgroup analysis of leukemic patients suggested that patients in the induction phase of therapy have a higher rate of bacteremia and pneumonia. No substantial difference in course or outcome was seen between the leukemia and solid tumor groups, possibly because of the intensive treatment administered to pediatric patients with solid tumors. Risk assessment strategies based on chemotherapy dose intensity and patient comorbidities rather than underlying malignancy should be prospectively studied. PMID- 11778608 TI - Feline fortunes: contrasting perceptions of cats. PMID- 11778610 TI - Veterinary medicine and the American Civil War. PMID- 11778609 TI - Evolution of exotic medicine through zoological gardens. PMID- 11778611 TI - [Contribution to the hospital history of Montauban]. PMID- 11778612 TI - [Agencies for infant care, 1900-1918]. PMID- 11778613 TI - [The public charity of Senlis in the seventeenth and eighteenth centuries]. PMID- 11778614 TI - [From the royal abbey of Val-de-Grace to the military hospital]. PMID- 11778615 TI - [Blindess in France from the medieval period to the 19th century]. PMID- 11778616 TI - [Administrators of the General D'Annonany Hospital, 1686-1796]. PMID- 11778617 TI - [Sainte-Marthe in Avignon from hospital to university]. PMID- 11778618 TI - Neonatal mortality and stillbirths in early twentieth century Derbyshire, England. AB - Neonatal mortality and stillbirths are recognised to be subject to similar influences, but survival after a successful live birth is usually considered in isolation of foetal wastage. Moreover, individual-level data on age-specific influences and causes of death in a historical context are rare. This paper uses an unusual data set to compare the influences on neonatal mortality and stillbirths in early twentieth century Derbyshire, England. Multivariate hazard and logistic analyses are performed to examine the relative roles of various social, environmental, and demographic factors. The influences on and causal structures of neonatal mortality and stillbirths emerge as broadly similar, with previous reproductive history linked to a considerable amount of variation. The clustering of endogenous deaths was much greater than the clustering of exogenous and post-neonatal deaths, probably reflecting the cause-of-death structure and the relatively healthy social and environmental position of early twentieth century Derbyshire. PMID- 11778619 TI - Population pressure and fertility in pre-transition Thailand. AB - Before the demographic transition in Thailand, fertility was high, but not uniformly so. As in other pre-transition settings, Thai fertility responded to pressures and opportunities created by socioeconomic structure and land availability. Drawing upon provincial data from the 1947 and 1960 censuses of Thailand, we find a strong 'frontier effect' on Thai fertility in the 1950s. Fertility was higher in sparsely settled frontier provinces and lower in provinces with higher population density relative to cultivatable land. This finding is robust and holds up with controls for agricultural employment, land quality, and the sex ratio (an indicator of sex-selective migration). The effect of population pressure lowers the likelihood of marriage and of marital fertility. The findings from Thailand are consistent with the research of Easterlin on the nineteenth century United States and with other pre-transition societies. We suggest how demographic transition theory might be broadened to include fertility dynamics in pre-transition societies. PMID- 11778620 TI - Mortality following conjugal bereavement, Belgium 1991-96: the unexpected effect of education. AB - This paper examines excess mortality following spousal bereavement by time since bereavement, sex, age, and education. The main hypothesis challenged is that higher education buffers the harmful effects of spousal loss. Using a log-rate model, death-rate ratios (widowed/married) are estimated for 49,849 and 126,746 Belgian widowers and widows and an equal number of non-bereaved controls matched to the bereaved on their socio-demographic characteristics. The hypothesis that the more educated suffer less excess mortality is not supported. Although higher educational levels are associated with lower mortality in general, they do not alleviate the effects of bereavement. On the contrary, in the period immediately following spousal loss, the more highly educated seem to have more, rather than less, excess mortality. Three possible arguments are suggested to account for this: education-related differences in the partner-relationship, structural differences in the availability of appropriate social support, and cultural differences in potential support networks. PMID- 11778621 TI - Excess mortality of girls in the Middle East in the 1970s and 1980s: patterns, correlates and gaps in research. AB - Comparative research on girls' excess mortality in the Middle East is rare. Estimates from the United Nations suggest that absolute excess mortality of girls was not universal in the 1970s and was uncommon by the 1980s. Compared with historical Northwest Europe at similar levels of boys' under-five mortality, however, girls' under-five mortality was high in both periods. Studies of the allocation of food and health care suggest that parents invested less and provided less curative care to girls than boys where girls' excess mortality was greatest. Urbanization and women's relative economic opportunity account for much of the variation in relative mortality. Unexplained excess mortality of girls in the Middle East compared with historical Northwest Europe may be attributable to differences in socio-cultural, political, and economic systems that influence the forms of discrimination exercised against girls; however, inadequate measurement of these variables limits their consideration in comparative research. PMID- 11778622 TI - Fertility transition in Communist Albania, 1950-90. AB - In 1945, at the end of the Second World War, Albania had the highest fertility in Europe with an average of more than six live births per woman. However, when Albania emerged from behind the 'olive curtain' in 1990, fertility had fallen to three children per woman, despite a pro-natalist environment and in the virtual absence of contraception and abortion. Nevertheless, after five decades, Albania's position at the top of the European fertility league remains unchanged. This paper documents the fertility transition in Albania during the period 1950 90 and places the demographic results in the context of recent socio-economic and cultural change. PMID- 11778623 TI - Board of Veterans' Appeals: rules of practice--notice of appeal in simultaneously contested claim. Final rule. AB - The Board of Veterans' Appeals (Board) adjudicates appeals from denials of claims for veterans' benefits filed with the Department of Veterans Affairs (VA). This document amends a Board Rule of Practice, pertaining to a type of notice given in simultaneously contested claim appeals, to eliminate an inconsistency between that Rule of Practice and an Appeals Regulation and to update a presumption related to communication of the notice. PMID- 11778624 TI - Medicare and Medicaid programs; physicians' referrals to health care entities with which they have financial relationships: partial delay of effective date. Interim final rule with comment period; partial delay in effective date. AB - This interim final rule with comment period delays for 1 year the effective date of the last sentence of 42 CFR 411.354(d)(1). Section 411.354(d)(1) was promulgated in the final rule entitled "Medicare and Medicaid Programs; Physicians' Referrals to Health Care Entities With Which They Have Financial Relationships," published in the Federal Register on January 4, 2001 (66 FR 856). A 1-year delay in the effective date of the last sentence in Section 411.354(d)(1) will give Department officials the opportunity to reconsider the definition of compensation that is "set in advance" as it relates to percentage compensation methodologies in order to avoid unnecessarily disrupting existing contractual arrangements for physician services. Accordingly, the last sentence of Section 411.354(d)(1), which would have become effective January 4, 2002, will not become effective until January 6,2003. PMID- 11778625 TI - Medicare and state health care programs: fraud and abuse; ambulance replenishing safe harbor under the anti-kickback statute. Final rule. AB - This final rule sets forth a safe harbor, as authorized under section 14 of the Medicare and Medicaid Patient and Program Protection Act of 1987, to protect certain arrangements involving hospitals or other receiving facilities that replenish drugs and medical supplies used by ambulance providers (or first responders) when transporting patients to the hospitals or receiving facilities. PMID- 11778626 TI - Copayments for inpatient hospital care and outpatient medical care. Interim and final rule. AB - This document amends VA's medical regulations to set forth a mechanism for determining copayments for inpatient hospital care and outpatient medical care. This is necessary to implement provisions of the Veterans Millennium Health Care and Benefits Act and to set forth exemptions from copayment requirements as mandated by statute. PMID- 11778627 TI - Copayments for medications. Final rule. AB - This document amends VA's medical regulations to set forth copayment requirements for medications. This is necessary to implement provisions of the Veterans Millennium Health Care and Benefits Act. PMID- 11778629 TI - Filipino veterans' benefits improvements. Interim final rule. AB - This document amends Department of Veterans Affairs (VA) adjudication regulations to reflect changes made by the Departments of Veterans Affairs and Housing and Urban Development, and Independent Agencies Appropriations Act, 2001, which changed the rate of compensation payments to certain Filipino veterans residing in the United States and the Veterans Benefits and Health Care Improvement Act of 2000, which changed the amount of the burial benefit paid to the survivors of certain Filipino veterans who were residing in the United States at the times of their deaths. PMID- 11778630 TI - [Famous medical historian: Arpad Herczeg]. PMID- 11778631 TI - Medicare and Medicaid programs; emergency recertification for coverage for organ procurement organizations (OPOs). Interim final rule with comment period. AB - This interim final rule with comment period recertifies the existing designated organ procurement organizations (OPOs) that meet, or have met, the standards for a qualified OPO within a 4 year period ending December 31, 2001 and have current agreements with the Secretary that are scheduled to terminate on July 31, 2002. Those agreements will be extended to July 31, 2006. The Organ Procurement Organization Certification Act of 2000 amended the Public Health Service Act to require CMS to increase the certification cycle for OPOs from 2 years to at least 4 years. We are issuing this interim final rule to establish a 4 year recertification cycle and to permit payments to continue to be made to all 59 OPOs after January 1, 2002. PMID- 11778632 TI - The ticket to work and self-sufficiency program. Final rules. AB - We are publishing final regulations implementing the Ticket to Work and Self Sufficiency Program (Ticket to Work program) authorized by the Ticket to Work and Work Incentives Improvement Act of 1999. The Ticket to Work program provides beneficiaries with disabilities with expanded options for access to employment services, vocational rehabilitation services, or other support services. We will pay the providers of those services after the beneficiaries achieve certain levels of work. PMID- 11778633 TI - [The mystery of the disappearing insects]. PMID- 11778634 TI - Intact cross-modality text-specific repetition priming in patients with Alzheimer's disease. AB - This study was aimed at investigating the basic mechanisms of the normal repetition priming evoked by text re-reading procedures in Alzheimer's disease (AD) patients (Monti, Gabrieli, Wilson, & Reminger, 1994; Monti et al., 1997). For this purpose, we contrasted the reading facilitation elicited by previous reading or listening to a text in a sample of AD patients and a group of age matched normal controls. Consistent with previous evidence in normal undergraduates (Levy & Kirsner, 1989), previous listening to a text decreased the successive reading time of the same text (cross-modality priming). However, the reading facilitation elicited by previous reading of the same text (within modality priming) was significantly larger than the facilitation evoked by previous listening. Compared to normal controls, AD patients showed intact cross modality and within-modality priming. These data are discussed in the light of alternative hypotheses regarding the basic mechanisms of impaired and spared repetition priming in degenerative demented patients. PMID- 11778635 TI - Declarative memory in early Parkinson's disease: serial position learning effects. AB - This study tested the question of whether executive failure associated with frontal lobe deficit is associated with, and therefore, may influence declarative memory dysfunction in Parkinson's disease (PD). A variety of memory and 'frontal sensitive' tasks were used. The 'frontal lobe dysfunction' hypothesis was tested in part, by examining the serial position effects (SPE) of word list learning across five successive trials. The relationship between memory and 'frontal sensitive' task scores was tested also. A total of 39 PD patients early in the course of the disease and 31 matched controls were included in the study. The PD subjects showed mild memory deficits in comparison to the healthy control group. In the face of any hypothesized selective 'dysexecutive' syndrome in PD group, the latter groups learning strategy across five trials did not differ from that of the control group. Also, the expected interrelation between memory and 'frontal sensitive' scores was not obtained. Therefore, the hypothesis that frontal dysfunction alone may account for memory impairments in PD is not fully supported. PMID- 11778636 TI - Visuospatial deficits in Parkinson's disease assessed by judgment of line orientation test: error analyses and practice effects. AB - The Benton's Judgment of Line Orientation (JLO) is one of the tests most frequently used to assess visuospatial function. The aim of the present study was to analyze qualitative errors in Parkinson's disease (PD) following the method described by Ska, Poissant, and Joanette (1990) and to determine possible practice effects of this test. The JLO was administered to 76 idiopathic PD patients and 76 matched normal controls. The analyses of errors showed several qualitative differences between groups. Parkinson's patients made a greater proportion of complex intraquadrant errors and horizontal line errors, while they showed fewer simple intraquadrant errors than controls. The JLO test was also administered twice in an interval of 20 min in a subsample of 25 PD patients and 25 normal controls. The results did not show significant differences between the two administrations, indicating that the test is free of practice effects. In conclusion, these data provide further evidence for the existence of visuospatial deficits in PD. Moreover, the JLO has proved to be an appropriate test for the assessment of the visuospatial function in patients who require a neuropsychological follow up. PMID- 11778637 TI - How to assess spatial neglect--line bisection or cancellation tasks? AB - Spatial neglect is usually assessed using cancellation tests or line bisection. A recent comparison of these tests has revealed a double dissociation, in which one neglect patient was impaired in line bisection but not in star cancellation whereas another showed the reverse deficit. This dissociation has prompted the question whether 'neglect' is still a meaningful theoretical entity. We compared line bisection and cancellation tasks regarding their accuracy in detecting spatial neglect. We tested 35 patients with well-defined spatial neglect using a line bisection task and four different cancellation tasks. The line bisection test missed 40% of our neglect patients. Far superior were the letter cancellation and bells tests, each of which missed only 6% of the cases. A deviation in line bisection is not fundamentally related to spatial neglect, but may also arise from other causes (e.g., hemianopia, or which hand is used), and therefore, should be treated with caution in clinical diagnosis. Cancellation tests, such as the bells test and letter cancellation, are more helpful tools to detect spatial neglect. PMID- 11778638 TI - Adult age differences in self-ordered pointing task performance: contributions from working memory, executive function and speed of information processing. AB - This study investigated adult age differences in, and predictors of, the performance of a test of executive function, the Self-Ordered Pointing Task (SOPT; Petrides & Milner, 1982). Performance on the SOPT is thought to rely on high level working memory processes, therefore, measures reflecting the common operationalization of working memory, along with measures of executive function and speed of information processing, were investigated as predictors of SOPT performance. Younger (aged 17-48 years) and older (aged 65-88 years) adults completed a 16-item, 3-trial, modified version of Shimamura and Jurica's (1994) version of the SOPT, and tests assessing working memory, executive function and speed. Results showed that younger adults made fewer errors on the SOPT. There was no age difference in the frequency of use of a clustering strategy. Contrary to expectations, working memory was not a good predictor of individual or age differences in SOPT performance. Instead, speed of processing, and to a lesser extent, measures of perseverations, made larger unique and overlapping contributions to the variance. The SOPT and its association, or dissociation, with other measures of working memory may be useful for research into the nature of working memory and executive function and the theoretical links between them. PMID- 11778639 TI - Visual determinants of reduced performance on the Stroop color-word test in normal aging individuals. AB - It is unknown to what extent the performance on the Stroop color-word test is affected by reduced visual function in older individuals. We tested the impact of common deficiencies in visual function (reduced distant and close acuity, reduced contrast sensitivity, and color weakness) on Stroop performance among 821 normal individuals aged 53 and older. After adjustment for age, sex, and educational level, low contrast sensitivity was associated with more time needed on card I (word naming), red/green color weakness with slower card 2 performance (color naming), and reduced distant acuity with slower performance on card 3 (interference). Half of the age-related variance in speed performance was shared with visual function. The actual impact of reduced visual function may be underestimated in this study when some of this age-related variance in Stroop performance is mediated by visual function decrements. It is suggested that reduced visual function has differential effects on Stroop performance which need to be accounted for when the Stroop test is used both in research and in clinical settings. Stroop performance measured from older individuals with unknown visual status should be interpreted with caution. PMID- 11778640 TI - Intransitive limb gestures and apraxia following unilateral stroke. AB - Apraxia is the loss of the ability to perform learned, skilled movements correctly, and is frequently attributed to left hemisphere damage (Heilman & Rothi, 1985). Recent work (Dumont, Ska, & Schiavetto, 1999) has shown a dissociation between transitive (tool based; e.g., hammering a nail) and intransitive (expressive/ communicative; e.g., waving goodbye) actions; however, few group studies have specifically addressed apraxia for intransitive gestures. The present investigation examined the frequency and severity of praxis errors related to the production of intransitive gestures in left (LHD) or right hemisphere stroke (RHD) patients in the context of Roy's (1996) model of limb praxis. A total of 119 consecutive stroke patients (LHD = 57, RHD = 62) and 20 healthy age-matched controls performed eight intransitive gestures to pantomime and imitation. Performance was quantified via a multi-dimensional error notation system, providing detail about specific elements of performance (e.g., location), and a composite score reflecting overall gestural accuracy. Analyses of pantomime and imitation performance revealed an equal percentage of apraxic patients in each stroke group, and the severity of apraxia in these groups was also equivalent. Further, analyses of the patterns of apraxia specified by Roy (1996) revealed that patients in each stroke group demonstrated selective impairments in pantomime (LHD = 38%, RHD = 42%), or imitation (LHD = 9%, RHD = 5%) conditions, whereas others demonstrated concurrent impairments (LHD = 30%, RHD = 22%) indicating that stroke to either hemisphere can selectively impair each stage in the production of an intransitive action. PMID- 11778641 TI - Neuropsychological test performance: a study of non-Hispanic White elderly. AB - This study examined within-group differences in neuropsychological test performance between US versus foreign-born English-speaking White elders. Participants included 193 randomly selected English-speaking elderly community residents who self-identified as non-Hispanic White. Participants were classified as US (n = 106) or foreign-born (n = 87). All participants were independently diagnosed by a physician as nondemented. After controlling for years of education, participants born in the United States obtained significantly higher scores on measures of verbal abstract reasoning, naming, and fluency than foreign born elders. These results suggest that although non-Hispanics White are often treated as a homogeneous group, performance differences exist even within this group. Effects of acculturation level and language use on cognitive styles may help explain these findings. PMID- 11778642 TI - Characteristics of self-reported memory compensation in older adults. AB - Self-reported efforts to compensate for memory impairments in everyday life were examined. In seven scales, the Memory Compensation Questionnaire (MCQ) measures five mechanisms of memory compensation, as well as motivation to compensate and awareness of need to compensate. The MCQ was administered twice, at a 3-year interval, to a large sample of healthy older adults (aged initially 55-85 years) from the Victoria Longitudinal Study. Concurrent analyses (n = 854) revealed an excellent set of psychometric properties for the MCQ and its scales. Two-wave longitudinal analyses (n = 629) revealed overall short-term stability of compensatory strategy use. Although all groups reported a similar pattern of relative frequencies of compensatory mechanism use, select qualifications of age and gender were detected. Applications of the MCQ to investigate awareness, motivation, and implementation of compensatory memory strategies in various populations are discussed. PMID- 11778643 TI - Voluntary and automatic visual spatial shifts of attention in Parkinson's disease: an analysis of costs and benefits. AB - Visual spatial shifts of attention were investigated in 13 patients suffering from Parkinson's disease and 20 control subjects. Attention was directed towards a target location with peripheral or central cues at varying SOAs in two separate experiments. A benefit and cost analysis was conducted on reaction times. The results of the central cueing task showed that in comparison with control subjects, costs of invalid cueing were reduced in patients. Results of the peripheral cueing task revealed that although the cueing effect (valid-invalid) was similar for patients and controls, the effect of valid cueing (neutral-valid) was greater in patients. The effects observed in both tasks were explained as an impaired ability of patients with Parkinson's disease to maintain attention. PMID- 11778644 TI - Long-term consequences of severe closed head injury on episodic memory. AB - This is the first systematic investigation of the very long-term effects of severe closed head injury (CHI) on objective measures of memory, and the first to employ both a normal control group and an 'other injury' control group consisting of spinal cord injury (SCI) patients. The CHI group displayed significantly poorer performance on every memory measure, and the effect sizes were large. This impairment in episodic memory is neither due to pre-injury nor post-injury differences between CHI and normal control subjects because the same differences were found when the CHI group was compared to a group of SCI patients. The findings demonstrate severe impairment in learning and retention many years after sustaining a severe CHI, which is likely in part due to the bilateral hippocampal damage shown in neuropathological studies. This life-long memory impairment needs to be addressed by community service programs. PMID- 11778645 TI - "Damn the precision, full speed ahead with the clinical interpretation.". AB - The purpose of this report is to respond to Dr. Cicchetti's (1999) challenge of the minimum of 400 subjects suggested by Charter (1999) for split-half, coefficient alpha, retest, alternate-forms, validity, and inter-rater reliability coefficients. PMID- 11778646 TI - The precision of reliability and validity estimates re-visited: distinguishing between clinical and statistical significance of sample size requirements. PMID- 11778647 TI - Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children. AB - It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis. PMID- 11778648 TI - Relationship of the K-ras/c-mos expression patterns with angiogenesis in non small cell lung carcinomas. AB - BACKGROUND: Neo-angiogenesis is an acquired capability vital for a tumor to grow and metastasize. Evidence has shown that the mitogen-activated protein (MAP) kinase pathway is involved in this process. Alterations of K-ras and c-mos, two pivotal components of this pathway, have been implicated in non-small cell lung carcinogenesis. In the present report, we examine, in a series of non-small cell lung carcinomas (NSCLCs), the status of K-ras and c-mos oncoproteins in correlation with the tumor neo-angiogenesis state and the major angiogenic factor, vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: c-mos and p-ERK1/2 status was evaluated immunohistochemically in a total of 65 NSCLCs, whereas the presence of K-ras mutations was examined by reverse transcriptase polymerase chain reaction (RT-PCR) restriction fragment length polymorphism (RFLP) in available matched normal tumor material from 56 cases. Microvessel density (MVD) was estimated by immunodetection of CD3, endothelial marker, and VEGF expression was assessed by immunohistochemistry. All possible associations were examined by a series of statistical methods. RESULTS: Expression of oncogenic activated K-ras and c-mos overexpression was observed in 12 of 49 (25%) and in 16 of 61 (26%) informative cases, respectively. Only 1 of the 25 deregulated for K-ras or c-mos cases exhibited both alterations, suggesting a mutually exclusive relationship between activated K-ras and c-mos overexpression (p = 0.074) in a subset of NSCLCs. In these cases, the MAPK kinase kinase/MEK/ERK pathway was found to be activated. MVD and VEGF expression were 36.9 +/- 10.6 mv/mm2 and 73.1 +/- 20.0%, respectively. The most intriguing finding was that the [K-ras(No)/c-mos(P)] profile was significantly associated with low MVD levels compared to normal cases (p = 0.004); by contrast, no correlation was found between the other K-ras/c-mos patterns and MVD. Furthermore, the former group exhibited the lowest VEGF levels. CONCLUSIONS: The mutually exclusive relationship between mutated K-ras and c-mos overexpression in a subset of NSCLCs implies a common signal transduction pathway in lung carcinogenesis. The effect of this pathway on NSCLC neo-angiogenesis seems to depend upon the status of c mos, which acts as a molecular "switch," possibly exerting a negative selective pressure on tumor progression. PMID- 11778649 TI - VEGF-D is an X-linked/AP-1 regulated putative onco-angiogen in human glioblastoma multiforme. AB - BACKGROUND: Glioblastoma multiforme (GBM) is a hypervascularized and locally infiltrating brain tumor of astroglial origin with a very poor prognosis. An X linked c-fos oncogene-inducible mitogenic, morphogenic, and angiogenic factor, endothelial growth factor-D (VEGF-D), is the newest mammalian member of VEGF family. We analyzed VEGF-D in GBM because of its high angiogenic potential and its linkage to the X chromosome. MATERIALS AND METHODS: Nonmalignant brain and GBM tissue sections as well as GBM cell lines were analyzed by immunofluorescence for the expression of VEGF-D, factor VIII (endothelial cell marker), glial fibrillary acidic protein (GFAP) (astrocytic cell lineage cytoplasmic marker), and several Fos family transcription factors, including c-Fos and Fra-1. The proteins were also detected by Western blots. The differences between genotypes of normal brain and GBM cells were examined by cDNA microarrays. RESULTS AND CONCLUSIONS: GBM expressed ubiquitously VEGF-D, which colocalized with GFAP. Contrary to our expectations, low levels of c-Fos were detected in GBM cells. However, we identified another Fos family member, Fra-1, together with its transcriptional activation partner, c-Jun, as being stably up-regulated in GBM cells. Furthermore, we demonstrated that a fra-1 transgene induced VEGF-D expression in cultured cells and GBM cell stimulation evoked a sustained increase in both Fra-1 and VEGF-D levels. This study reveals that an up-regulation of AP-1 factors may be a hallmark of GBM. Because VEGF-D activates VEGF receptor 2 and 3, receptors important for tumor angiogenesis, it may represent an X-linked/AP-1 regulated onco-angiogen in human GBM. The VEGF-D system and AP-1 activity appear to be very attractive targets for new molecular diagnostics and rational molecular anti-cancer therapies. PMID- 11778651 TI - Characterization of a novel hemoglobin-glutathione adduct that is elevated in diabetic patients. AB - BACKGROUND: Typically, a diagnosis of diabetes mellitus is based on elevated circulating blood glucose levels. In an attempt to discover additional markers for the disease and predictors of prognosis, we undertook the characterization of HbA1d3 in diabetic and normal patients. MATERIAL AND METHODS: PolyCAT A cation exchange chromatography and liquid chromatography-mass spectroscopy was utilized to separate the alpha- and beta-globin chains of HbA1d3 and characterize their presence in normal and diabetic patients. RESULTS: We report the characterization of HbA1d3 as a glutathionylated, minor hemoglobin subfraction that occurs in higher levels in diabetic patients (2.26 +/- 0.29%) than in normal individuals (1.21 +/- 0.14%, p < 0.001). The alpha-chain spectrum displayed a molecular ion of m/z 15126 Da, which is consistent with the predicted native mass of the HbA0 alpha-globin chain. By contrast, the mass spectrum of the beta-chain showed a mass excess of 307 Da (m/z = 16173 Da) versus that of the native HbA0 beta-globin chain (m/z = 15866 Da). The native molecular weight of the modified beta-globin chain HbA0 was regenerated by treatment of HbA1d3 with dithiothreitol, consistent with a glutathionylated adduct. CONCLUSIONS: We propose that HbA1d3 (HbSSG) forms normally in vivo, and may provide a useful marker of oxidative stress in diabetes mellitus and potentially other pathologic situations. PMID- 11778650 TI - The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. AB - BACKGROUND: High levels of A beta in the cerebral cortex distinguish demented Alzheimer's disease (AD) from nondemented elderly individuals, suggesting that decreased amyloid-beta (A beta) peptide clearance from the brain is a key precipitating factor in AD. MATERIALS AND METHODS: The levels of A beta in brain and plasma as well as apolipoprotein E (ApoE) in brain were investigated by enzyme-linked immunosorbent assay (ELISA) and Western blotting at various times during the life span of the APP23 transgenic (Tg) and control mice. Histochemistry and immunocytochemistry were used to assess the morphologic characteristics of the brain parenchymal and cerebrovascular amyloid deposits and the intracellular amyloid precursor protein (APP) deposits in the APP23 Tg mice. RESULTS: No significant differences were found in the plasma levels of A beta between the APP23 Tg and control mice from 2-20 months of age. In contrast, soluble A beta levels in the brain were continually elevated, increasing 4-fold at 2 months and 33-fold in the APP23 Tg mice at 20 months of age when compared to the control mice. Soluble A beta42 was about 60% higher than A beta40. In the APP23 Tg mice, insoluble A beta40 remained at basal levels in the brain until 9 months and then rose to 680 microg/g cortex by 20 months. Insoluble A beta40 was negligible in non-Tg mice at all ages. Insoluble A beta42 in APP23 Tg mice rose to 60 microg/g cortex at 20 months, representing 24 times the control A beta42 levels. Elevated levels of ApoE in the brain were observed in the APP23 Tg mice at 2 months of age, becoming substantially higher by 20 months. ApoE colocalized with A beta in the plaques. Beta-amyloid precursor protein (betaAPP) deposits were detected within the neuronal cytoplasm from 4 months of age onward. Amyloid angiopathy in the APP23 Tg mice increased markedly with age, being by far more severe than in the Tg2576 mice. CONCLUSIONS: We suggest that the APP23 Tg mouse may develop an earlier blockage in A beta clearance than the Tg2576 mice, resulting in a more severe accumulation of A beta in the perivascular drainage pathways and in the brain. Both Tg mice reflect decreased A beta elimination and as models for the amyloid cascade they are useful to study AD pathophysiology and therapy. PMID- 11778652 TI - The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. AB - BACKGROUND: Angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) act on the endothelial cell Tie-2 receptor to regulate vascular integrity and remodeling. The local balance of these factors and the level of other angiogenic factors determine whether blood vessels grow, are maintained or regress. Profound angiogenesis and vascular remodeling occur in the placenta and this is altered in preeclampsia, a major cause of maternal and fetal morbidity and mortality. MATERIALS AND METHODS: The mRNAs encoding Ang-1, Ang-2, and Tie-2 were detected and localized in human placentae throughout gestation. The mechanism of regulation angiopoietin mRNAs level was determined by explant culture in ambient and reduced oxygen, and in the presence of actinomycin D. RESULTS: In situ hybridization showed that Ang-2 mRNA was abundant in the syncytiotrophoblast in the first trimester of human pregnancy. Ang-1 mRNA could not be detected by in situ hybridization, but was by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting. Placental vascular structure is altered in preeclampsia and intrauterine growth restriction, conditions where feto-placental oxygenation is perturbed. In villous explant cultures, a reduction in oxygen tension significantly raised the levels of Ang-2 mRNA, and this was dependent on transcription. However, similar experiments showed that the stability of the Ang 1 message was greatly reduced under these conditions. Thus, hypoxia has opposite effects on Ang-1 and Ang-2 mRNA levels. Placentae obtained from women with preeclampsia had reduced levels of Ang-2 mRNA compared to gestationally matched controls. There was no difference in the levels of Ang-1 mRNAs. CONCLUSIONS: These data show that the relative levels of Ang-1 and Ang-2 mRNA are regulated by local oxygen tension by different mechanisms and that this may be important during normal human placentation. PMID- 11778653 TI - Differential susceptibility of naive and activated human gammadelta T cells to activation-induced cell death by T-cell receptor cross-linking. AB - BACKGROUND: T cells undergo activation-induced cell death (AICD) through repeated stimulation of their T cell receptors (TCRs). Activated human gammadelta T cells were found to die by apoptosis when their TCRs were cross-linked by antibodies, whereas naive gammadelta T cells freshly isolated from blood did not. Therefore, we investigated the factors that could contribute to this differential susceptibility. MATERIALS AND METHODS: Gammadelta T cells were isolated from the peripheral blood of healthy human volunteers and their TCRs were cross-linked either directly (naive) or after an in vitro incubation of 11 days (activated). Their cell cycle profiles, cytokine, Fas and FasL mRNA messages, and surface expression of Fas and FasL were determined. RESULTS: The naive cells were cycling while the activated T cells exited from the G1 to subG1 phase upon TCR cross linking. IL-2 and IL-4 mRNAs and surface expression of FasL were detected only in activated T cells in the time period examined. In addition, cFLIP mRNA expression was found only in naive gammadelta T cells and activated T cells treated with cyclosporin A (CsA), which inhibited AICD in the activated T cells. CsA also downregulated the surface expression of FasL in activated T cells. CONCLUSIONS: The differential expression of cytokines, apoptotic inducers and inhibitors provide the basis for the differential susceptibility of naive and activated gammadelta T cells to AICD upon TCR cross-linking. This contributes to our understanding of the regulation and maintenance of gammadelta T-cell homeostasis, which would be important in many infectious as well as autoimmune diseases, where gammadelta T cells have been implicated. PMID- 11778654 TI - BAX contributes to apoptotic-like death following neonatal hypoxia-ischemia: evidence for distinct apoptosis pathways. AB - BACKGROUND: Hypoxic-ischemic (H-I) injury to the neonatal brain has been shown to result in rapid cell death with features of acute excitotoxicity/necrosis as well as prominent delayed cell death with features of apoptosis such as marked caspase 3 activation. BAX, a pro-apoptotic molecule, has been shown to be required for apoptotic neuronal cell death during normal development but the contribution of endogenous BAX in cell death pathways following H-I injury to the developing or adult brain has not been studied. MATERIALS AND METHODS: Bax +/+, +/-, and -/- mice at post-natal day 7 were subjected to unilateral carotid ligation followed by exposure to 45 minutes of 8% oxygen. At different timepoints following H-I, brain tissue was studied by conventional histology, immunohistochemistry, immunofluorescence, Western blotting, and enzymatic assay to determine the extent and type of cell injury as well as the amount of caspase activation. RESULTS: We found that bax -/- mice had significantly less (38%) hippocampal tissue loss than mice expressing bax. Some of the remaining cell death in bax -/- mice, however, still had features of apoptosis including evidence of nuclear shrinkage and caspase-3 activation. Though bax -/- mice had significantly decreased caspase-3 activation as compared to bax expressing mice following H-I, the density of cells with activated caspase-8 in the CA3 region of the hippocampus did not differ between bax +/- and bax -/- mice. CONCLUSIONS: These findings demonstrate that endogenous BAX plays a role in regulating cell death in the central nervous system (CNS) following neonatal H-I, a model of cerebral palsy. In addition, while BAX appears to modulate the caspase-3 activation following neonatal H-I, caspase-8 which is linked to death receptor activation, may contribute to apoptotic-like neuronal death in a BAX-independent manner. PMID- 11778655 TI - A novel protocol that allows short-term stem cell expansion of both committed and pluripotent hematopoietic progenitor cells suitable for clinical use. AB - To obtain long-term engraftment and hematopoiesis in myeloablated patients, the cell population used for hematopoietic reconstitution should include a sufficient number of early pluripotent hematopoietic stem cells (HSCs), along with committed cells from the various lineages. For this purpose, the small subset of CD34+ cells purified from different sources must be expanded ex vivo. Since cytokines may induce both proliferation and differentiation, expansion would provide a cell population comprising committed as well as uncommitted cells. Optimization of HSC expansion methods could be obtained by a combination of cytokines able to sustain renewal of pluripotent cells yet endowed with poor differentiation potential. We used variations of the combinations of cytokines described by Brugger et al. [W. Brugger, S. Heimfels, R. J. Berenson, R. Mertelsmann, and L. Kanz (1995) N. Engl. J. Med. 333, 283-287] and Piacibello et al. [W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta (1997) Blood 89, 2644-2653] to expand UCB CD34+ cells and monitored proliferation rate and phenotype after 14 days of culture. Several hematopoietic lineage-associated surface antigens were evaluated. Our data show that flt3L and thrombopoietin in combination with IL-3, while sustaining a high CD34+ proliferation rate, provide a relatively low enrichment in very early uncommitted CD34+/CD38- cells. Conversely, in the absence of IL-3, they are less effective in inducing proliferation yet significantly increase the number of CD34+/CD38- cells. A combination of the above protocols, applied simultaneously to aliquots of the same sample, would allow expansion of both committed and pluripotent HSC. This strategy may represent a significant improvement for clinical applications. PMID- 11778656 TI - Synergy between TLR2 and TLR4: a safety mechanism. AB - BACKGROUND: The Toll (Tlr) receptors facilitate innate immunity by detecting products that are unique to invading microorganisms. Stimulation of these receptors can produce severe reactions and death. We propose that synergy between receptors for different microbial products would provide a safety mechanism, preventing inappropriate, potentially fatal reactions by reacting to low concentrations of ligands when more than a single ligand is present. RESULTS: Striking synergy is noted between the ligand for Tlr4, lipopolysaccharide (LPS), and a ligand for Tlr2, muramyl dipeptide (MDP), in the release of tumor necrosis factor from RAW cells. CONCLUSIONS: Synergy between a ligand for Tlr2 and Tlr4 can be demonstrated in a simple in vitro system. The greater sensitivity of MDP stimulated cells to LPS may explain the data that were once interpreted incorrectly as indicating that Tlr2 is the endotoxin receptor. PMID- 11778657 TI - Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties. AB - In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed. PMID- 11778658 TI - Linkage to chromosome 1q in Greek families with juvenile hemochromatosis. AB - Hereditary hemochromatosis (HH) is a genetically heterogeneous disease. The HFE gene resides on chromosome 6 and its mutations account for the majority of HH cases in populations of northern European ancestry. Recently, two new types of hemochromatosis have been identified: Juvenile hemochromatosis (JH or HFE2), which maps to chromosome 1q21, and an adult form defined as HFE 3, which results from mutations of the TFR 2 gene, located at 7q22. We have performed a linkage study in five unrelated families of Greek origin with non-HFE hemochromatosis. Linkage at the chromosome 1q21 JH locus was detected in affected members with the use of polymorphic markers. Comparison of haplotypes between Greek and Italian JH patients revealed the presence of a common haplotype. However, the fact that many other haplotypes carrying the JH defect were observed in the two populations indicates that the respective mutations may have occurred in different genetic backgrounds. We suggest that hemochromatosis patients without HFE mutations should be evaluated for other possible types of hemochromatosis since hemochromatosis type 3 (HFE3) has a clinical appearance similar to HFE 1, and JH may have a late onset in some cases. PMID- 11778659 TI - The dual association between lymphoma and autoimmunity. AB - Autoimmune rheumatic diseases and lymphocytic malignancies are related and this association is bidirectional. Lymphomas occur more frequently in the course of autoimmune disease and autoimmune rheumatic manifestations occur in the course of lymphocytic malignancies. An increased incidence of malignant lymphocytic diseases is present in patients with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, and autoimmune thyroid disease. Descriptions of lymphocytic malignancies among other autoimmune rheumatic disease have been published. In some patients, the malignant disease is diagnosed months or years before the appearance of the rheumatic disease. PMID- 11778660 TI - Preliminary classification of nonmalignant B cell proliferation in Sjogren's syndrome: perspectives on pathobiology and treatment based on an integrated clinico-pathologic and molecular study approach. AB - A classification of nonmalignant lymphoproliferation in Sjogren's syndrome is presented, based on the results of international meetings regarding Sjogren's syndrome-associated lymphomagenesis and on our results of a clinico-pathologic and molecular study and long-term follow-up in well-characterized patients. Sjogren's syndrome pathobiology has similarities to hepatitis C virus-related B cell lymphoproliferation. Antigen stimulation with the preferential expansion of rheumatoid factor-positive clones and specific immunoglobulin gene expression and recombination represent key biologic events in lymphoproliferation. This classification is based on the coupling of molecular and histological studies and may result in more selective treatment approaches. PMID- 11778661 TI - An erythroid-specific chromatin opening element reorganizes beta-globin promoter chromatin structure and augments gene expression. AB - In erythroid tissues the chromatin structure of the beta-globin gene locus is extensively remodeled. Changes include the formation of DNase I hypersensitive sites (HSs) over the promoters of actively expressed genes. To test the hypothesis that such "opening" of promoter chromatin structure is important for beta-globin gene expression, we placed a 101-bp erythroid-specific hypersensitive site forming element (HSFE) from the core of LCR HS4 immediately upstream of a minimal beta-globin gene promoter. We then studied the effects of this element alone and in combination with other cis-acting elements on globin gene chromatin structure and gene expression in MEL cells and transgenic mice. Single or tandem HSFEs increased the size of the portion of the promoter accessible to DNase digestion, increased the proportion of promoters in an accessible conformation, and increased gene expression approximately 5-fold. These were equivalent to expression levels attained using a 2.8-kb microLCR construct. Inclusion of the LCR HS2 enhancer did not increase expression further. In transgenic mouse fetal liver cells the HSFE increased average expression 2.5-fold compared to the minimal promoter alone. These results indicate that a small cis-acting element is capable of remodeling local beta-globin promoter chromatin structure and producing expression similar to that seen with a microLCR construct. PMID- 11778662 TI - Lead poisoning prevention, not chelation (commentary). PMID- 11778663 TI - Lead poisoning treatment--a continuing need (commentary). PMID- 11778664 TI - Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water. AB - BACKGROUND: Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. METHODS: Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/ 14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1 propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. RESULTS: Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo treated cases. CONCLUSION: 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement. PMID- 11778665 TI - Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs. AB - OBJECTIVE: To evaluate the effects of arsenic (III) exposure on porphyrin metabolism and the central nervous system supplemented with data on the effect of hepatic and renal tissues of rats and guinea pigs. METHODS: Rats and guinea pigs were exposed to 10 or 25 ppm arsenic in drinking water for 16 weeks. RESULTS: Following chronic arsenic (III) exposure, delta-aminolevulinic acid dehydratase activity in blood showed a significant reduction as did the total cell counts (RBC and WBC) and reduced glutathione with increased urinary delta-aminolevulinic acid. Zinc protoporphyrin, a sensitive indicator of iron deficiency and impairment of heme biosynthesis, showed a significant increase in arsenic exposure. The hepatic delta-aminolevulinic acid dehydratase and delta aminolevulinic acid synthetase activity increased in chronic arsenic (III) exposure in rats and guinea pigs. Significant changes in the steady-state level of three major neurotransmitters, dopamine, norepinephrine, and 5 hydroxytryptamine, and monoamine oxidase were observed following chronic arsenic (III) exposure. CONCLUSION: At low doses (10 and 25 ppm in drinking water), the effects of arsenic on hematopoietic indices and whole-brain neurotransmitter concentrations were more prominent in guinea pigs than in rats with some variability in the dose response. PMID- 11778666 TI - Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary. AB - Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement was evident with and without neuropathy. Electrodiagnostic studies proved helpful for the diagnosis of neurological involvement. Advanced neglected cases with many years of exposure presented with cancer of skin and of the lung, liver, kidney, and bladder. The diagnosis of subclinical arsenicosis was made in 83%, 93%, and 95% of hair, nail and urine samples, respectively, in Bangladesh; and 57%, 83%, and 89% of hair, nail, and urine samples, respectively in West Bengal. Approximately 90% of children below 11 years of age living in the affected areas show hair and nail arsenic above the normal level. Children appear to have a higher body burden than adults despite fewer dermatological manifestations. Limited trials of 4 arsenic chelators in the treatment of chronic arsenic toxicity in West Bengal over the last 2 decades do not provide any clinical, biochemical, or histopathological benefit except for the accompanying preliminary report of clinical benefit with dimercaptopropanesulfonate therapy. Extensive efforts are needed in both countries to combat the arsenic crisis including control of tube-wells, watershed management with effective use of the prodigious supplies of surface water, traditional water management, public awareness programs, and education concerning the apparent benefits of optimal nutrition. PMID- 11778667 TI - Urinary mercury excretion following amalgam filling in children. AB - OBJECTIVES: Dental amalgam is the major source of inorganic mercury exposure in the general population. Dental amalgam contains approximately 50% mercury, which is a toxic element. Since children are more at risk for mercury toxicity, we aimed to study prospectively the effects of amalgam filling on urinary mercury excretion in 5- to 7-year-old children. METHODS: Children admitted to the Pedodontics Department with no previous amalgam filling, and in a good state of health with one or more carious posterior teeth, were selected. All fillings were placed in one session for each child using Sina (Iran) amalgam powder and Degussa (Germany) mercury, which were mixed by an automated electric amalgamator (Dentomate 3, Germany). Urinary mercury concentrations were estimated before and 9-12 days after amalgam filling by atomic absorption using the mercuric hydride system. RESULTS: Forty-three children (20 male, 23 female) aged 5.95+/-0.92 years and weighing 19.09+/-3.10 kg were studied. Urinary mercury concentrations before and after amalgam filling were 3.83+/-2.45 and 5.14+/-3.14 microg/L, respectively (p = 0.001). There were no statistically significant correlations between the urinary mercury concentrations and any other variables, including the number and surfaces of filled teeth, weight, age, and sex. CONCLUSION: Although there were highly significant increases in urinary mercury concentrations after amalgam filling, no significant correlation was found between the urinary mercury concentration and the amounts of filled amalgam. Additional investigation is required concerning the effects of mercury release from amalgam. PMID- 11778668 TI - Toxicologists and the assessment of risk: the problem with mercury (commentary). PMID- 11778670 TI - Hepatotoxicity in acute iron poisoning. AB - Although hepatotoxicity is a known sequela of acute iron poisoning, the literature describing it is confined to sporadic reports. Key issues such as prognosis and whether this is a dose-related phenomenon are not addressed. Review of this literature and of experimental animal studies demonstrates that it occurs early in the clinical course and has a relatively high mortality. The lowest acute serum iron concentration associated with hepatotoxicity was 1700 microg/dL (304 micromol/L). Since this greatly exceeds the reference range of 50-150 microg/dL (9-27 micromol/L), it supports a dose-related etiology. Unlike most other hepatotoxins, the periportal areas of the hepatic lobule are the primary sites of injury. As this is the principle sitefor hepatic regeneration, this accountsfor the relatively high mortality rate. An understanding of the pathogenesis of the hepatotoxicity of acute iron poisoning is central to the identification of rational and effective interventions. From the clinical perspective, the relatively high mortality rate of iron poisoning-induced hepatotoxicity requires vigilance for its onset and earlier consideration of liver transplantation. PMID- 11778669 TI - Neurotoxicology of the brain barrier system: new implications. AB - The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood cerebrospinal fluid barrier. Evidence in the past decades suggests that brain barriers are subject to toxic insults from neurotoxic chemicals circulating in blood. The aging process and some disease states render barriers more vulnerable to insults arising inside and outside the barriers. The implication of brain barriers in certain neurodegenerative diseases is compelling, although the contribution of chemical-induced barrier dysfunction in the etiology of any of these disorders remains poorly understood. This review examines what is currently understood about brain barrier systems in central nervous system disorders by focusing on chemical-induced neurotoxicities including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3 nitropropionic acid. Contemporary research questions arising from this growing understanding show enormous promises for brain researchers, toxicologists, and clinicians. PMID- 11778671 TI - Lead poisoning and chelation in a mother-neonate pair. AB - We report the case of a pregnant woman with chronic lead toxicity and a blood lead of 57 microg/dL (2.7 micromol/L) who gave birth to a healthy-appearing neonate with a cord blood lead of 126 microg/dL (6.08 micromol/L). The mother was prescribed a single course of oral succimer late in the third trimester of pregnancy, without any appreciable change in her blood lead. The neonate was initially treated with intramuscular dimercaprol and intravenous edetate calcium disodium. After 3 days, the neonate was then switched to oral 2,3 dimercaptosuccinic acid because the blood lead had declined. The child received two 19-day courses of 2,3-dimercaptosuccinic acid and had a blood lead level of 21.5 microg/dL (1.04 micromol/L) at 5 months of age. Despite extensive investigation, the precise source of the mother's lead toxicity remained undetermined. PMID- 11778672 TI - Intravenous mercury injection and ingestion: clinical manifestations and management. AB - BACKGROUND: Mercury is a complex toxin with clinical manifestations determined by the chemical form, route, dose, and acuity of the exposure. Parenteral injection of elemental mercury remains uncommon. CASE REPORT: A 40-year-old male injected 3 mL of elemental mercury intravenously and ingested 3 mL as a suicide attempt. Within 24 hours, he became dyspneic, febrile, tachycardic, and voiced mild gastrointestinal complaints. Chest X-ray revealed scattered pulmonary infiltrates and embolized mercury bilaterally. A ventilation/perfusion scan demonstrated ventilation/ perfusion deficits. Additionally, his renal function declined, as manifest by minor elevations in blood urea nitrogen and creatinine and decreased urine output. Pulmonary therapy, intravenous hydration, and chelation using 2,3 dimercaptoscuccinic acid (DMSA/Succimer) were started. Over the next 36 hours, the patient's pulmonary and renal functions improved. Temperature and heart rate subsequently normalized, and symptoms at discharge were mild exertional dyspnea. DISCUSSION: Liquid mercury injected intravenously embolizes to the pulmonary vasculature and perhaps vessels in other organs such as heart and kidney. In-situ oxidation to inorganic mercury, which is directly toxic to a variety of tissues, may help explain the multisystem involvement. CONCLUSION: Significant pulmonary dysfunction accompanied by radiographically demonstrated mercury emboli and temporary abnormalities in several organs improved shortly after initiation of chelation. The impact of chelation on long-term outcome of parenteral mercury exposure remains uncharacterized. PMID- 11778674 TI - New approaches to missing data in psychological research: introduction to the special section. AB - Traditional approaches to missing data (e.g., listwise deletion) can lead to less than optimal results in terms of bias, statistical power, or both. This article introduces the 3 articles in the special section of Psychological Methods, which consider multiple imputation and maximum-likelihood methods, new approaches to missing data that can often yield improved results. Computer software is now available to implement these new methods. PMID- 11778673 TI - Cholestatic hepatitis caused by acute gold potassium cyanide poisoning. AB - INTRODUCTION: Poisoning after oral ingestion of gold potassium cyanide is rarely reported. A case of suicidal ingestion of gold potassium cyanide (potassium dicyanoaurate; CAS# 13967-50-5) is described. CASE REPORT: A 27-year-old man attempted suicide by ingesting 5 mL gold potassium cyanide solution. He developed vomiting, hyperamylasemia, and hepatic dysfunction. Cyanide poisoning was not detected but acute gold toxicity was noted. Pathologic findings of the liver showed centrilobular cholestasis with eosinophilic degeneration. The whole blood and serum gold were 4361 and 6011 microg/L, respectively, and the 24-hour urine gold was 429 microg/d in samples obtained on day 4. CONCLUSION: Gold-induced hepatotoxicity has been seen infrequently in patients receiving gold therapy. Reported agents include sodium aurothiomalate, sodium aurothiopropranol sulfonate, aurothioglucose, aurothiopolypeptide (Auro-detoxin), auric sulfide, and gold thiosulfate, our report adds gold potassium cyanide. PMID- 11778675 TI - The use of multiple imputation for the analysis of missing data. AB - This article provides a comprehensive review of multiple imputation (MI), a technique for analyzing data sets with missing values. Formally, MI is the process of replacing each missing data point with a set of m > 1 plausible values to generate m complete data sets. These complete data sets are then analyzed by standard statistical software, and the results combined, to give parameter estimates and standard errors that take into account the uncertainty due to the missing data values. This article introduces the idea behind MI, discusses the advantages of MI over existing techniques for addressing missing data, describes how to do MI for real problems, reviews the software available to implement MI, and discusses the results of a simulation study aimed at finding out how assumptions regarding the imputation model affect the parameter estimates provided by MI. PMID- 11778676 TI - A comparison of inclusive and restrictive strategies in modern missing data procedures. AB - Two classes of modern missing data procedures, maximum likelihood (ML) and multiple imputation (MI), tend to yield similar results when implemented in comparable ways. In either approach, it is possible to include auxiliary variables solely for the purpose of improving the missing data procedure. A simulation was presented to assess the potential costs and benefits of a restrictive strategy, which makes minimal use of auxiliary variables, versus an inclusive strategy, which makes liberal use of such variables. The simulation showed that the inclusive strategy is to be greatly preferred. With an inclusive strategy not only is there a reduced chance of inadvertently omitting an important cause of missingness, there is also the possibility of noticeable gains in terms of increased efficiency and reduced bias, with only minor costs. As implemented in currently available software, the ML approach tends to encourage the use of a restrictive strategy, whereas the MI approach makes it relatively simple to use an inclusive strategy. PMID- 11778677 TI - The impact of nonnormality on full information maximum-likelihood estimation for structural equation models with missing data. AB - A Monte Carlo simulation examined full information maximum-likelihood estimation (FIML) in structural equation models with nonnormal indicator variables. The impacts of 4 independent variables were examined (missing data algorithm, missing data rate, sample size, and distribution shape) on 4 outcome measures (parameter estimate bias, parameter estimate efficiency, standard error coverage, and model rejection rates). Across missing completely at random and missing at random patterns, FIML parameter estimates involved less bias and were generally more efficient than those of ad hoc missing data techniques. However, similar to complete-data maximum-likelihood estimation in structural equation modeling, standard errors were negatively biased and model rejection rates were inflated. Simulation results suggest that recently developed correctives for missing data (e.g., rescaled statistics and the bootstrap) can mitigate problems that stem from nonnormal data. PMID- 11778678 TI - Evaluating statistical difference, equivalence, and indeterminacy using inferential confidence intervals: an integrated alternative method of conducting null hypothesis statistical tests. AB - Null hypothesis statistical testing (NHST) has been debated extensively but always successfully defended. The technical merits of NHST are not disputed in this article. The widespread misuse of NHST has created a human factors problem that this article intends to ameliorate. This article describes an integrated, alternative inferential confidence interval approach to testing for statistical difference, equivalence, and indeterminacy that is algebraically equivalent to standard NHST procedures and therefore exacts the same evidential standard. The combined numeric and graphic tests of statistical difference, equivalence, and indeterminacy are designed to avoid common interpretive problems associated with NHST procedures. Multiple comparisons, power, sample size, test reliability, effect size, and cause-effect ratio are discussed. A section on the proper interpretation of confidence intervals is followed by a decision rule summary and caveats. PMID- 11778679 TI - Effects of study duration, frequency of observation, and sample size on power in studies of group differences in polynomial change. AB - Consider a study in which 2 groups are followed over time to assess group differences in the average rate of change, rate of acceleration, or higher degree polynomial effect. In designing such a study, one must decide on the duration of the study, frequency of observation, and number of participants. The authors consider how these choices affect statistical power and show that power depends on a standardized effect size, the sample size, and a person-specific reliability coefficient. This reliability, in turn, depends on study duration and frequency. These relations enable researchers to weigh alternative designs with respect to feasibility and power. The authors illustrate the approach using data from published studies of antisocial thinking during adolescence and vocabulary growth during infancy. PMID- 11778680 TI - Random assignment of available cases: bootstrap standard errors and confidence intervals. AB - A frequently used experimental design in psychological research randomly divides a set of available cases, a local population, between 2 treatments and then applies an independent-samples t test to either test a hypothesis about or estimate a confidence interval (CI) for the population mean difference in treatment response. C. S. Reichardt and H. F. Gollob (1999) established that the t test can be conservative for this design-yielding hypothesis test P values that are too large or CIs that are too wide for the relevant local population. This article develops a less conservative approach to local population inference, one based on the logic of B. Efron's (1979) nonparametric bootstrap. The resulting randomization bootstrap is then compared with an established approach to local population inference, that based on randomization or permutation tests. Finally, the importance of local population inference is established by reference to the distinction between statistical and scientific inference. PMID- 11778681 TI - The role of method in treatment effectiveness research: evidence from meta analysis. AB - A synthesis of 319 meta-analyses of psychological, behavioral, and educational treatment research was conducted to assess the influence of study method on observed effect sizes relative to that of substantive features of the interventions. An index was used to estimate the proportion of effect size variance associated with various study features. Study methods accounted for nearly as much variability in study outcomes as characteristics of the interventions. Type of research design and operationalization of the dependent variable were the method features associated with the largest proportion of variance. The variance as a result of sampling error was about as large as that associated with the features of the interventions studied. These results underscore the difficulty of detecting treatment outcomes, the importance of cautiously interpreting findings from a single study, and the importance of meta analysis in summarizing results across studies. PMID- 11778682 TI - Computing and evaluating factor scores. AB - A variety of methods for computing factor scores can be found in the psychological literature. These methods grew out of a historic debate regarding the indeterminate nature of the common factor model. Unfortunately, most researchers are unaware of the indeterminacy issue and the problems associated with a number of the factor scoring procedures. This article reviews the history and nature of factor score indeterminacy. Novel computer programs for assessing the degree of indeterminacy in a given analysis, as well as for computing and evaluating different types of factor scores, are then presented and demonstrated using data from the Wechsler Intelligence Scale for Children-Third Edition. It is argued that factor score indeterminacy should be routinely assessed and reported as part of any exploratory factor analysis and that factor scores should be thoroughly evaluated before they are reported or used in subsequent statistical analyses. PMID- 11778683 TI - Replication status as a possible marker for genomic instability in cells originating from genotypes with balanced rearrangements. AB - Most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle. However, some genes frequently replicate asynchronously, i.e. genes on the X chromosome and imprinted genes. Earlier studies demonstrated an asynchronous pattern of replication in some precancerous and invasive squamous carcinoma of the cervix as well as in multiple myeloma. A high rate of asynchronous pattern was found in: (1) lymphocytes of individuals with solid tumors as well as in other malignancies; (2) amniocytes of genotypes with an extra chromosome 13, 18 and 21; (3) lymphocytes of young mothers of a Down syndrome pregnancy. The asynchronic pattern was not locus specific and was found in all loci analyzed. These findings suggested that the mechanism controlling the temporal order of replication could be altered in cells with a genetic predisposition to cancer or aneuploidy. In this study, we found a higher rate of asynchronous pattern in genotypes carrying inversions 2 and 9 and in balanced heritable translocations (p < 0.01) and an even higher rate in cases with a de-novo balanced translocation. The process of tumorigenesis may begin with a change in cell cycle regulation which includes the duplication, replication and segregation of genetic information. However, it remains unknown whether individuals with balanced chromosome rearrangements are at increased risk of developing cancer later in life. PMID- 11778684 TI - Syntenic assignment of sixteen genes from the long arm of human chromosome 10 to bovine chromosomes 26 and 28: refinement of the comparative map. AB - A comparative mapping approach was applied in order to refine the extent and the distribution of conserved segments between the long arm of human chromosome 10 (HSA10) and cattle chromosomes 26 and 28 (BTA26 and BTA28 respectively). Sixteen genes localised on the long arm of HSA10 were mapped using a bovine-hamster somatic cell hybrid panel: twelve represent new assignments in cattle; the four others are in agreement with previous published data. This study confirms and refines the boundaries of the disruption zones between HSA10 and, BTA26 and BTA28, at the level of the human cytogenetic band. PMID- 11778685 TI - Correspondence of human chromosomes 9, 12, 15, 16, 19 and 20 with donkey chromosomes refines homology between horse and donkey karyotypes. AB - Whole chromosome paints for human (HSA) chromosomes 9, 12, 15 and 20 and arm specific paints for HSA16p, 19p and 19q were applied on donkey metaphase spreads. All probes, except HSA19p, gave distinct hybridization signals on donkey chromosomes/chromosomal segments. The results show direct segmental homology between human and donkey genomes, and enable refinement of correspondence between donkey and horse karyotypes. Of specific interest is the identification of hitherto unknown correspondence between four equine acrocentric chromosomes (ECA22, 23, 25 and 28) and the donkey chromosomes. Overall, the findings mark the beginning of an ordered study of comparative organization of genomes/karyotypes of the equids, that can shed light on karyotype evolution and ancestral chromosomal condition in the Perissodactyls. PMID- 11778686 TI - Gene assignment in Ateles paniscus chamek (Platyrrhini, Primates). Allocation of 18 markers of human syntenic groups 1, 2, 7, 14, 15, 17 and 22. AB - Eighteen markers allocated to human syntenic groups 1, 2, 7, 14, 15, 17 and 22 were assigned to the chromosome complement of the neotropical primate Ateles paniscus chamek. These new allocations and existing gene charts in this species were compared with chromosome painting patterns produced by human chromosome probes in the congeneric species A teles geoffroyi and with available data on the human genome and gene mapping. These comparisons showed congruent findings in Ateles and provided good evidence of how several human syntenic groups were evolutionarily rearranged. PMID- 11778687 TI - Construction of comparative cytogenetic maps of the Chinese hamster to mouse, rat and human. AB - We constructed comparative cytogenetic maps of the Chinese hamster to mouse, rat and human by fluorescence in-situ hybridization using 36 cDNA clones of mouse, rat, Syrian hamster, Chinese hamster and human functional genes. In this study, 30 out of the 36 genes were newly mapped to Chinese hamster chromosomes. The chromosomal homology of the Chinese hamster was identified and arranged in 19, 19 and 18 segments of conserved synteny in mouse, rat and human, respectively. Additionally, two of the 19 segments homologous to mouse chromosomes were initially identified in this study. PMID- 11778688 TI - Molecular cytogenetic analysis of a novel high-grade canine T-lymphoblastic lymphoma demonstrating co-expression of CD3 and CD79a cell markers. AB - We present the molecular cytogenetic analysis of a novel case of canine lymphoma, in a nine-year-old entire male collie cross retriever dog that presented with an enlarged prescapular lymph node. A diagnosis of high-grade lymphoblastic lymphoma was made by histological evaluation of fixed lymph node biopsy sections, whilst immunohistochemical analyses demonstrated co-expression of B- and T-cell antigens (CD79a and CD3) by 95% of lymphomatous cells. Comparative genomic hybridisation (CGH) analysis detected loss of dog chromosomes 11, 30 and 38 and gain of chromosome 36 within the lymphoma biopsy specimen. These findings correlated with direct cytogenetic analysis of tumour metaphases using whole chromosome paint probes representing each of these four chromosomes. This study represents the first report of the combined application of both direct and indirect cytogenetic techniques for the analysis of recurrent chromosome aberrations in canine cancer. PMID- 11778689 TI - Meiotic chromosomes and stages of sex chromosome evolution in fish: zebrafish, platyfish and guppy. AB - We describe SC complements and results from comparative genomic hybridization (CGH) on mitotic and meiotic chromosomes of the zebrafish Danio rerio, the platyfish Xiphophorus maculatus and the guppy Poecilia reticulata. The three fish species represent basic steps of sex chromosome differentiation: (1) the zebrafish with an all-autosome karyotype; (2) the platyfish with genetically defined sex chromosomes but no differentiation between X and Y visible in the SC or with CGH in meiotic and mitotic chromosomes; (3) the guppy with genetically and cytogenetically differentiated sex chromosomes. The acrocentric Y chromosomes of the guppy consists of a proximal homologous and a distal differential segment. The proximal segment pairs in early pachytene with the respective X chromosome segment. The differential segment is unpaired in early pachytene but synapses later in an 'adjustment' or 'equalization' process. The segment includes a postulated sex determining region and a conspicuous variable heterochromatic region whose structure depends on the particular Y chromosome line. CGH differentiates a large block of predominantly male-specific repetitive DNA and a block of common repetitive DNA in that region. PMID- 11778690 TI - Cytogenetic comparison between Vietnamese sika deer and cattle: R-banded karyotypes and FISH mapping. AB - R-banded chromosomes of Vietnamese sika (VS) deer (Cervus nippon pseudaxis, 2N = 66), a threatened subspecies of sika deer endemic to Vietnam, are presented for the first time and were compared with bovine R-banded chromosomes to define a standard karyotype. Nineteen VS deer autosomes (CNP) were identified on the basis of the banding pattern relative to bovine chromosomes (BTA), while hypotheses for the remaining thirteen were proposed from comparisons with the published deer genetic map, BTA 1, 2, 5, 6, 8 and 9 each equivalent to two separate acrocentric CNP chromosomes and BTA 26 and 28 associated in a tandem fusion. To confirm these hypotheses, probes for the twenty-nine Texas nomenclature type I markers specific for each cattle autosome, sixteen other type I and fourteen microsatellite markers were used in FISH experiments on VS deer chromosomes. CNP7 presented the most complex rearrangement as compared with cattle chromosomes. A complete correspondence between VS deer and cattle chromosomes was established and it was extended with a comparison with the human karyotype to transfer human map information to this species of scientific and economic interest. Moreover, this work anchors the deer genetic linkage map to chromosome-specific markers. PMID- 11778691 TI - Molecular cytogenetic characterization of the EBV-producing cell line B95-8 (Saguinus oedipus, Platyrrhini) by chromosome sorting and painting. AB - The cell line B95-8 releases Epstein-Barr virus (EBV) with high titres of transforming activity and is widely used as a model in cancer research and virology. There are, however, controversial reports about the species of origin, cell line stability and karyotype. To address these questions, B95-8 chromosomes were analysed by chromosome sorting and painting by multicolour fluorescence in situ hybridization. Reciprocal painting was performed between B95-8, 'wildtype' New World monkey and human chromosomes. Saguinus oedipus was revealed as the species of origin. A further five cell-line-specific marker chromosomes, resulting from translocations, deletions and an insertion were found. Although human chromosome 6 or 13 homologues were always involved in these rearrangements, co-hybridization of an EBV-specific DNA probe did not reveal site-specific hybridization to marker chromosomes or at translocation breakpoints. The multicolour probe set described here will be of special value for further evolutionary studies in New World monkeys. PMID- 11778692 TI - Characterization of a cluster of late genes of guinea pig cytomegalovirus. AB - Human cytomegalovirus (HCMV) is the most common congenital infection, and is associated with a high rate of morbidity and mortality in the newborn infant. Guinea pig cytomegalovirus (GPCMV) is transmitted through the placenta with resulting fetal infection, and provides an excellent model for the study of fetal cytomegalovirus infection. We have characterized a cluster of late GPCMV genes, identifying GPCMV homologs of the HCMV G protein-coupled receptor gene, UL33; the transcriptional repressor gene, UL34 and two genes encoding tegument proteins, UL32 and UL35. We also identified the GPCMV homolog of UL37, an antiapoptotic gene. Surprisingly, no GPCMV homolog to HCMV UL36 was identified in the same genomic region. Furthermore, two of the predicted GPCMV proteins share greater identity with HHV-6 and/or HHV-7 homologs than with other cytomegalovirus homologs. The identification of GPCMV homologs of conserved viral genes, particularly genes involved in pathogenicity such as the G protein-coupled receptors, will facilitate future analysis of the role of these genes in infections. PMID- 11778693 TI - High variability of HTLV-I in a remote population of Gabon as compared to that of a similar population of French Guiana. AB - An anomalous high frequency of ATL was observed in a remote 'noir maroons' village of French Guiana. Since it is not clear if HTLV-I is responsible for different frequencies of disease in different geographical areas, we undertook a comparison of the population with a similar one located in Gabon. We found a much higher degree of gp46 surface envelope glycoprotein sequence conservation in the Guianese village than in the Gabonese one. PMID- 11778694 TI - Interleukin-2-dependent but not independent T-cell lines infected with human T cell leukemia virus type 1 selectively express CD45RO, a marker for persistent infection in vivo. AB - Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia. HTLV-1 is exclusively detected in CD45RO+ T-cells in infected individuals, but CD45RO is weakly expressed in HTLV-1-transformed T-cell lines in vitro. The aim of this study was to investigate the role of CD45RO in the persistent HTLV-1 infection in vivo. Flow cytometry showed that only two out of eight interleukin(IL)-2-independent HTLV-1-transformed T-cell lines expressed CD45RO, whereas all five IL-2-dependent ones expressed CD45RO, and the level of expression was higher in IL-2-dependent than in IL-2-independent cells. The high CD45RO expression in IL-2-dependent cell lines was not due to IL-2, since IL-2 had little effect on the expression of CD45RO in T-cell lines. Using western blotting, we showed that IL-2-dependent HTLV-1-transformed T-cell lines expressed a lower level of expression of the viral transcriptional regulatory protein Tax than IL-2-independent ones, and that the level of expression correlated inversely with that of CD45RO. However, the expression of Tax in one HTLV-1-negative T-cell line little affected the expression of CD45RO, suggesting that Tax at least alone does not suppress the expression of CD45RO in HTLV-1-infected T-cell lines, and that other viral or cellular factor(s) are probably involved in such suppression. Our results suggest that CD45RO+ Tax-low IL-2-dependent T-cell lines in vitro correspond to the persistent HTLV-1-infected cells in vivo, and HTLV-1-infected cells in vivo are immortalized in IL-2-dependent manner. PMID- 11778695 TI - Gene expression analyzed by microarrays in HSV-1 latent mouse trigeminal ganglion following heat stress. AB - An understanding of the cellular genes whose expression is altered during HSV reactivation will enable us to better understand host responses and biochemical pathways involved in the process. Furthermore, this knowledge could allow us to develop gene-targeted inhibitors to prevent viral reactivation. Mice latent with HSV-1 strain McKrae and uninfected control mice were subjected to hyperthermic stress (43 degrees C for 10 min) and their trigeminal ganglia (TG) collected 1 h later. Two additional groups included HSV-1 latently infected and uninfected mice not subjected to hyperthermic stress. Poly A+ mRNA was enriched from total mouse TG RNA and reverse transcribed using MMLV RT. Radioactively labeled cDNAs were analyzed by microarray analysis. A stress/toxicology array of 149 mouse genes on a nylon membrane was used. The labeled cDNAs prepared from latently infected, stressed mice demonstrated 3-fold or greater increases in certain mRNA-early response genes (ERGs) compared to cDNAs from uninfected, stressed control mice. The ERG mRNAs that showed increases included two heat shock proteins (HSP60 and HSP40), a basic transcription factor (BTF T62), a DNA repair enzyme, two kinases [MAP kinase and a stress-induced protein kinase (SADK)], an oxidative stress induced protein, a manganese superoxide dismutase precursor-2 (SOD-2), and cyclooxygenase 2 (COX-2). The gene expression in unstressed, infected TGs was similar to the gene expression in unstressed, uninfected controls. These results suggest that there is a significant difference in the ERG expression profile in latently infected TGs undergoing stress-induced reactivation compared to uninfected TGs. PMID- 11778696 TI - A recombinant virus assay using full-length envelope sequences to detect changes in HIV-1 co-receptor usage. AB - The clinical management of HIV-1 infection has benefited enormously from molecular characterization of drug resistance as well as determination of the viral phenotype in vitro. HIV-1 infected individuals on HAART are currently monitored for the development of drug resistance variants allowing clinicians to redesign drug regimens. An understanding of the molecular basis of the evolution of drug resistance in vivo allows the improvement of the drugs as well as in vitro evaluation of new antiviral compounds alone or in combination with those currently approved. New findings suggest that viral envelopes could be a target to inhibit infection and replication. Therefore the generation of a recombinant virus assay (RVA) to allow the phenotypic determination of drug resistance against entry inhibitors (EI) is anticipated. We constructed an env-deleted clone of HIV-1 using the molecular clone NL-4.3. PCR amplified complete envelope genes (NL-4.3, BaL, primary envelope-genes) were ligated in vitro with a deletion clone (pNL-deltaK) and PM1-cells, supporting the replication of R5- and X4-tropic viruses, were transfected. Determination of co-receptor usage of the harvested recombinant virus-swarm revealed no difference compared to the molecular clones derived individually from three different patients. These results clearly show that an envelope-based RVA is practicable to monitor HIV-co-receptor usage at a given time point. Furthermore, this assay will allow to monitor resistance development against existing and future entry inhibitors and will aid to improve the management of HIV-therapy. PMID- 11778698 TI - Characterization of the myxoma virus M118L protein: a novel essential poxvirus IMV-associated protein. AB - Myxoma M118L ORF has the capacity to encode a 76 amino acid protein that is highly conserved in other vertebrate poxviruses including vaccinia (A30L), molluscum contagiosum (MC136L), yaba tumour virus (D13L) and fowlpox virus (FPV 194). The time course analysis by Western blotting using M118L antibody showed that the M118L ORF is expressed as a typical poxvirus late gene. The M118L protein can be detected in both the virus infected cytosolic and membrane fractions, even though the M118L protein does not possess a predicted transmembrane domain. The protein was found to be associated with the sucrose gradient purified myxoma intracellular mature virus (IMV) as determined by Western blotting with M118L antibody. Furthermore, the M118L protein associated with the IMV can be surface labeled with water-soluble biotin and is released from the purified IMV with treatment of nonionic detergent NP-40, indicating that the M118L protein is associated with the outer membrane of myxoma IMV. Unexpectedly, an IMV-associated M118L protein isoform was observed to bind tightly to Streptavidin beads, unlike the six other detectable myxoma IMV surface proteins, suggesting an unusual post-translational modification, such as biotinylation. Extensive attempts to generate the M118L deletion mutant using standard homologous recombination technique with E. coli gpt gene as a positive selection marker were unsuccessful. Although PCR analysis clearly indicated the presence of the correctly targeted M118L deletion mutants in mixed recombinant virus plaques selected with mycophenolic acid (MPA), repeated passages and plaquing failed to segregate the pure M118L deletion mutant from either single crossover recombinants or regenerated wild type parental viruses. Taken together, our data strongly indicate that the M118L is a novel poxvirus IMV associated protein that is essential for virus viability. PMID- 11778697 TI - Characterization of ATI, TK and IFN-alpha/betaR genes in the genome of the BeAn 58058 virus, a naturally attenuated wild Orthopoxvirus. AB - The lack of knowledge about the natural host of Vaccinia virus (VV) along with the description of human infections caused by poxviruses after smallpox eradication has increased the need to characterize poxviruses isolated from the wild. Moreover, in the past years poxviruses have been widely studied as potential vaccination tools, with the discovery of several genes implicated in the evasion of the host immune response involved in virus pathogenesis. Among them, an Interferon (IFN)-binding protein was identified in the supernatant of VV strain WR infected cells coded by the B18R gene. It was shown that many other Orthopoxviruses also encode and express this soluble receptor although some VV strains such as Lister and modified Ankara, which were less reactogenic vaccines, do not. The BeAn 58058 virus (BAV) has been recently characterized and proposed to be an Orthopoxvirus. BAV was also shown to be less virulent in animal models than VV Lister. Here we report the identification of an IFN-alpha/betaR gene in the BAV genome with 99% of sequence identity with the VVWR B18R gene. The identified gene encodes a B18R-like IFN binding protein as demonstrated by its capacity to inhibit the IFN-mediated protection of VERO cells against EMC virus. In order to better characterize the virus we have searched for the A type inclusion body (ATI) gene currently used in the classification of Orthopoxviruses but did not detect it in the BAV genome. We have also sequenced the BAV thymidine kinase (TK) gene, a poxvirus-conserved gene, which, as expected, showed high homology with the TK gene of other poxviruses. Phylogenetic trees were constructed based on sequences of the IFN-alpha/betaR and TK genes from several poxviruses and in both cases BAV was placed in the same cluster as other VV strains. These observations strengthened the hypothesis that this virus is a variant of the VV vaccine used in Brazil. However the explanation for the BAV lack of virulence remains to be discovered. PMID- 11778699 TI - Base-pair alterations in the epsilon-lower stem due to a novel double substitution in the precore gene of HBV-e negative variant were recovered by secondary mutations. AB - The HBe negative phenotype, a natural precore mutant (G1896A/G1897A) of HBV with aborted HBeAg expression is known to cause chronic hepatitis. The destabilized C : G base-pairing in the lower stem of epsilon-hairpin due to G1896A substitution is reportedly compensated by a second C1858T mutation and suggested to play an important role in enhanced selection of the HBe negative variant. We undertook to investigate presence of such compensatory mutations at other positions by analyzing epsilon-sequences (nts. 1847-1907) as well as to look for their effect(s), if any, on the consensus sequence of the overlapping core-initiator of HBe negative HBV variants in CLD patients. Three of the 5 HBe negative patients had classical G1896A mutation having a second compensatory mutation at nt. 1858. One patient showed an additional G1897A substitution, presenting as a novel precore stop codon mutation (UGG-->UAA), followed by a compensatory mutation at position 1857. In the third patient, a G1899A substitution was seen which compensated the impaired U at position 1855. Other substitution and deletion mutations were also observed in the remaining epsilon-hairpin, which however, did not produce any compensatory mutation. Further, all the precore variants showed a conserved G at position 1904, important for the optimal context of their core initiator which however, remained impaired with A (nt. 1850). Our results suggest that the nts. 1851-1859 and nts. 1895-1904 in the lower stem, and restoration of authentic base-pairings therein, maintain the structural integrity and stability of the epsilon-hairpin. This may have a role in the enhanced selection of the HBe negative variants and persistence of HBV infection in chronic liver disease patients. PMID- 11778700 TI - Nucleotide sequence analysis of rotavirus gene 11 from two tissue culture-adapted ATCC strains, RRV and Wa. AB - We report here nucleotide sequence and characterization of gene 11 from two tissue culture-adapted ATCC rhesus (RRV) and human (Wa) strains of rotavirus. Gene 11 sequence encodes a nonstructural protein, NSP5 and also encodes NSP6, from an out of phase open reading frame. Sequence of RRV(ATCC) gene 11 represents the first report from a rhesus rotavirus which has more than 90% homology at the nucleotide and deduced amino acid sequence level with that of its closely related simian SA11 strain. The WaATCC gene sequence differed from that of published Wa (WaPub) at three nucleotide positions, one at 264 (G(Wa-Pub) to A(ATCC-Wa)), another a nucleotide insertion (A) at position 388 and the third, a deletion (A) at 416. The latter two changes in WaATCC NSP5 resulted in drastic amino acid changes within a 10-residue region (123-132) from VHVYQFQLTN in WaPub to DSCVSISTNH in WaATCC NSP5 protein. In this region, WaATCC NSP5 is closer to published sequences from other strains, suggesting the authenticity of the present sequence. The nucleotide difference between WaPub and WaATCC NSP5 sequences, however, did not affect the NSP6 deduced amino acid sequence, which is overall highly conserved among all the strains compared. Sequence-based phylogenetic analysis of gene 11 identified a high degree of conservation within the Group A rotaviruses. In addition, it also separated RRV(ATCC) and WaATCC, suggesting rotavirus segregation by genogroup. An anti-NSP5 monoclonal antibody of SA11 recognized RRV NSP5 protein but not WaATCC NSP5 from the infected cells, further supporting the phylogenetic segregation of RRV(ATCC) and WaATCC strains based on their NSP5 coding sequence. PMID- 11778701 TI - Identification and phylogeny of a non-specific endonuclease gene of white spot syndrome virus of shrimp. AB - White spot syndrome virus (WSSV) is a taxonomically unclassified virus which causes a disease in shrimps worldwide. A 936 bp long open reading frame (ORF) was found on a 7.2 kb HindIII fragment of the DNA genome of WSSV located adjacent to the ribonucleotide reductase small subunit gene. This putative ORF showed homology to prokaryotic and eukaryotic endonucleases, which contain a non specific endonuclease motif. Alignment with viral and eukaryotic endonuclease ORFs revealed that most catalytically and structurally important amino acid residues were present in the putative WSSV non-specific endonuclease gene. An unrooted parsimonous phylogenetic tree of non-specific endonucleases indicated that the WSSV ORF was located in a well bootstrap supported clade containing only arthopods, including one of WSSV's natural hosts, Penaeus japonicus. A similar conjunction was found for the only other viral homologue, present in Fowlpox virus, which was also found in a well bootstrap-supported clade with its natural host, Gallus gallus. This clustering of virus and host suggests that both WSSV and Fowlpox virus may have acquired their nuclease genes from their respective natural hosts. Because the motif for non-specific nucleases is found in only two viruses, this gene cannot be used to clarify the taxonomic position of WSSV. However, the presence of this type of nuclease rarely found in viruses adds a novel feature to WSSV. PMID- 11778702 TI - Identification and sequence analysis of the glycoprotein B gene of porcine cytomegalovirus. AB - Porcine cytomegalovirus (PCMV) is one of the pathogens that should be eliminated from pigs intended for use as organ donors in xenotransplantation. For this purpose, reliable diagnostic test systems are needed. To provide a basis for this goal and to analyse the evolutionary relationships of PCMV within the herpesvirus family, the putative glycoprotein B (gB) gene of PCMV was identified by assuming gene colinearity and a relative conservation of nucleotide sequences in comparison with closely related herpesviruses. Using this approach the complete nucleotide sequence of the PCMV gB gene was determined. A protein of 860 amino acids was deduced and a putative cleavage site, conserved cysteine residues, as well as potential N-terminal glycosylation motifs were identified. In a comparison of PCMV gB with the corresponding region of other herpesviruses, the highest identities were found with human herpesviruses 6 and 7 (HHV-6 and 7; 43.4% and 42.6%, respectively). Also in phylogenetic analysis, the PCMV gB clustered with HHV-6 and HHV-7. Between the complete gB sequences of five different PCMV strains and isolates from the United Kingdom, Germany, Spain, Japan and Sweden, differences of 3.4% were found, indicating a considerable intra species variation. The characterisation of the protein deduced from the identified gene provides further evidence that this is indeed the gB gene of PCMV and provides important taxonomical information regarding PCMV. The identification of the gB gene should facilitate the development of sensitive and robust diagnostic methods for the PCMV screening of pigs. PMID- 11778703 TI - Comparison of the eIF-2alpha homologous proteins of seven ranaviruses (Iridoviridae). AB - The alpha-subunit of the eukaryotic initiation factor 2 (eIF-2alpha) is a key component of the translation machinery of the cell. In response to cellular stress such as viral infections, eIF-2alpha is phosphorylated by double-stranded RNA-dependent protein kinase (PKR) leading to the inhibition of cellular protein synthesis. The importance of eIF-2alpha as a regulatory mechanism for protein synthesis is illustrated by the wide variety of strategies employed by viruses to down-regulate PKR. Thus, Vaccinia virus encodes K3L protein, which resembles eIF 2alpha and acts as a pseudo-substrate inhibitor of PKR. Nucleotide sequencing of the genome of epizootic haematopoietic necrosis virus (EHNV), a member of the genus ranavirus of Iridoviridae, has revealed an eIF-2alpha equivalent gene. We have cloned and sequenced eIF-2alpha genes of several iridoviruses of fishes and frogs. The eIF-2alpha open reading frames and deduced proteins of the iridoviruses investigated exhibit a high degree of homology of both nucleotide and amino acid sequences. At the N-terminus, the iridoviral eIF-2alpha shows significant homology to the N-termini of cellular initiation factor 2-alpha of various species, to full-length poxviral eIF-2alpha proteins, and to the S1 domain of ribosomal proteins. Comparison of amino acid sequences of corresponding iridoviral proteins with eIF-2alpha homologous proteins of poxviruses and eukaryotes has revealed a high conservation of motifs. A phylogenetic analysis of eukaryotic eIF-2alpha and poxvirus and iridovirus eIF-2alpha sequences has demonstrated the relationship of these iridoviruses. In order to investigate the role of the eIF-2alpha equivalent, respective genes have been expressed in prokaryotic and eukaryotic (insect, fish and chicken cell) systems. The iridoviral eIF-2alpha protein has a molecular weight of 31 kDa and is cytoplasmic. The cellular and viral protein synthesis of iridoviruses is probably regulated by a mechanism similar to that of Vaccinia virus. Frog-virus 3, the type species of the genus ranavirus of Iridoviridae, has a unique translational efficiency and, moreover, down-regulates the cellular protein synthesis of infected cells. PMID- 11778704 TI - The amino acid region 248-382 of the Epstein-Barr virus nuclear protein 2 (EBNA2) is responsible for the EBNA2-induced EBV reactivation. AB - We showed previously that Epstein-Barr virus (EBV) latency is disrupted and the virus-replicative cycle is activated after expression of EBNA2 in the Burkitt's lymphoma-derived Akata cells. Here, an EBNA2 deletion mutant lacking the amino acid residues 248-382, including the region responsible for association with RBP J kappa, was generated and tested for its ability to activate EBV replication in Akata cells. This mutant was shown clearly deficient in inducing the EBV replicative cycle, suggesting that association with RBP-J kappa is necessary for the EBV activating function of EBNA2. It is thus likely that EBV activation by EBNA2, seemingly in conflict with its involvement in lymphocyte immortalization, is nevertheless based on the standard mechanism of transactivation by the protein. PMID- 11778705 TI - Brief presurgery hypnosis reduces distress and pain in excisional breast biopsy patients. AB - Each year, hundreds of thousands of women undergo excisional breast biopsies for definitive diagnosis. Not only do these patients experience pain associated with the procedure, but they also endure distress associated with the threat of cancer. Hypnosis has been demonstrated as effective for controlling patients' pain in other surgical settings, but breast surgery patients have received little attention. To determine the impact of brief presurgical hypnosis on these patients' postsurgery pain and distress and to explore possible mediating mechanisms of these effects, 20 excisional breast biopsy patients were randomly assigned to a hypnosis or control group (standard care). Hypnosis reduced postsurgery pain and distress. Initial evidence suggested that the effects of hypnosis were mediated by presurgery expectations. PMID- 11778707 TI - Hypnotic susceptibility scales: are the mean scores increasing? AB - The Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C), developed and named 37 years ago, is arguably the "gold standard" of hypnotic susceptibility scales. However, it has been the impression of several researchers that means obtained on the SHSS:C are higher now than in previous years. The authors comprehensively review studies using the SHSS:C over a 4-decade period. The findings demonstrate a significant linear trend between year and SHSS:C scores, with higher obtained means in more recent work. The authors also report a similar analysis of research with the Harvard Group Scale of Hypnotic Susceptibility, Form A. Although the mechanisms underlying this trend can only be speculated upon at present, these findings underscore the importance of using local control groups in research on hypnotizability. PMID- 11778706 TI - Hypnotizability and trauma symptoms after burn injury. AB - This study investigated the association of trauma symptoms and hypnotizability in 43 hospitalized survivors of burn injury. Three to 17 days after the injury, participants rated the frequency of intrusive and avoidance symptoms and were interviewed with the posttraumatic stress disorder module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders III-R. The Hypnotic Induction Profile was also administered at the postburn, hospital stage of recovery. Results indicated that when participants were divided into low, mid-range, and high hypnotizability categories, high hypnotizability was associated with more intrusive, avoidance, and arousal symptoms. Although causal relations cannot be assessed in this cross-sectional study, these results suggest that, as compared to the low and mid-range categories, high hypnotizables may experience a greater frequency of trauma symptoms after burn injury. PMID- 11778708 TI - Cultural scripts, memories of childhood abuse, and multiple identities: a study of role-played enactments. AB - This study compared the reports of satanic, sexual, and physical abuse of persons instructed to role-play either dissociative identity disorder (DID) (n = 33), major depression (n = 33), or a college student who experienced minor adjustment problems ("normal") (n = 33) across a number of trials that included role-played hypnosis. As hypothesized, more of the participants who were asked to role-play DID reported at least one instance of satanic ritual abuse and sexual abuse compared with those who role-played depression or a college student with minor adjustment problems. DID role-players reported more incidents of sexual abuse and more severe physical and sexual abuse than did the major depression role-players. Further, the DID role-players differed from the normal role-players on all the measures of frequency and severity of physical and sexual abuse. Participants in all groups reported more frequent and severe incidents of physical abuse after role-played hypnosis than they did prior to it. PMID- 11778710 TI - Designing lenses to correct peripheral refractive errors of the eye. AB - The purpose of this work was to design ophthalmic lenses that correct peripheral refractive errors of human eyes along a meridian. We designed lenses with the tangential section of one surface based on a figured spheroid but figured in the tangential section only. The curvature of the sagittal section of this surface was adjusted separately. A merit function was used to modify these surfaces until the lenses had power errors that corrected the eye. Examples are presented of lenses that correct a schematic eye. They do excellent jobs of correcting the peripheral power errors of the eye and are relatively insensitive to small changes in fitting distance. We conclude that it is theoretically feasible to design lenses to correct peripheral refractive errors. PMID- 11778711 TI - Multiple multipole method with automatic multipole setting applied to the simulation of surface plasmons in metallic nanostructures. AB - Highly accurate computations of surface plasmons in metallic nanostructures with various geometries are presented. Calculations for cylinders with irregular cross section, coupled structures, and periodic gratings are shown. These systems exhibit a resonant behavior with complex field distribution and strong field enhancement, and therefore their computation requires a very accurate numerical method. It is shown that the multiple multipole (MMP) method, together with an automatic multipole setting (AMS) procedure, is well suited for these computations. An AMS technique for the two-dimensional MMP method is presented. It relies on the global topology of each domain boundary to generate a distribution of numerically independent multipole expansions. This technique greatly facilitates the MMP modeling. PMID- 11778709 TI - Calculated impact of higher-order monochromatic aberrations on retinal image quality in a population of human eyes. AB - We calculated the impact of higher-order aberrations on retinal image quality and the magnitude of the visual benefit expected from their correction in a large population of human eyes. Wave aberrations for both eyes of 109 normal subjects and 4 keratoconic patients were measured for 3-, 4-, and 5.7-mm pupils with a Shack-Hartmann sensor. Retinal image quality was estimated by means of the modulation transfer function (MTF) in white light. The visual benefit was calculated as the ratio of the MTF when the monochromatic higher-order aberrations are corrected to the MTF corresponding to the best correction of defocus and astigmatism. On average, the impact of the higher-order aberrations for a 5.7-mm pupil in normal eyes is similar to an equivalent defocus of approximately 0.3 D. The average visual benefit for normal eyes at 16 c/deg is approximately 2.5 for a 5.7-mm pupil and is negligible for small pupils (1.25 for a 3-mm pupil). The benefit varies greatly among eyes, with some normal eyes showing almost no benefit and others a benefit higher than 4 at 16 c/deg across a 5.7-mm pupil. The benefit for keratoconic eyes is much larger. The benefit at 16 c/deg is 12 and 3 for 5.7- and 3-mm pupils, respectively, averaged across four keratoconics. These theoretical benefits could be realized in normal viewing conditions but only under specific conditions. PMID- 11778712 TI - Hollow beams of simple polarization for trapping and storing atoms. AB - We propose a scheme for producing and magnifying a hollow beam, as might be desired for purposes of storing and guiding cold atoms, through the use of a simple spherically aberrating lens and a projection lens. The field is a superposition of J0 Bessel fields, so that simple (linear, circular) polarizations can be utilized. analyze some of the beam properties through analytical approximations. Some examples of field zeros along the optical axis are given, together with some of their characteristics. Numerical calculations largely confirm the validity of the analytical expressions. For the most important zero nearly all of the beam power is contained within the first two Bessel spacings, with a resulting highly efficient trapping. Isophotes are calculated and displayed for the region surrounding this null point. They have regular shapes, for which we give an approximate expression. PMID- 11778713 TI - Patterns in the ripple structure of Mie scattering. AB - We study the ripple structure in the scattered intensity predicted by Mie scattering theory in the angular behavior of the scattered intensity for homogeneous, dielectric spheres. We find that for small values of the phase shift parameter rho = 2kR absolute value(m - 1), where k = 2 pi/lambda, R is the sphere radius, and m is the relative refractive index, the ripples are periodic with spacing equal to pi when plotted versus the dimensionless qR, where q = 2k sin(theta/2) and theta is the scattering angle. However, as rho increases, this outcome switches to nonuniform spacing of approximately pi cos(theta/2). The latter spacing is equivalent to a uniform spacing of pi/kR when plotted versus theta. PMID- 11778714 TI - Method for optimizing the correction of the eye's higher-order aberrations in the presence of decentrations. AB - The use of a correcting element to compensate for higher-order aberrations in an optical system often requires accurate alignment of the correcting element. This is not always possible, as in the case of a contact lens on the eye. We propose a method consisting of partial correction of every aberration term to minimize the average variance of the residual wave-front aberration produced by Gaussian decentrations (translations and rotations). Analytical expressions to estimate the fraction of every aberration term that should be corrected for a given amount of decentration are derived. To demonstrate the application of this method, three examples are used to compare performance with total and with partial correction. The partial correction is more robust and always yields some benefit regardless of the amount of decentration. PMID- 11778715 TI - Two theorems in catoptrics. AB - Two general theorems in the theory of mirrors are presented. The first one asserts that a mirror that reflects a parallel beam into a beam with zero mean curvature must be harmonic. The second one provides a universal characterization of the spot diagram of rays from a reflected parallel beam as they intersect a plane orthogonal to their direction of propagation. PMID- 11778716 TI - Contribution of the cornea and internal surfaces to the change of ocular aberrations with age. AB - We studied the age dependence of the relative contributions of the aberrations of the cornea and the internal ocular surfaces to the total aberrations of the eye. We measured the wave-front aberration of the eye with a Hartmann-Shack sensor and the aberrations of the anterior corneal surface from the elevation data provided by a corneal topography system. The aberrations of the internal surfaces were obtained by direct subtraction of the ocular and corneal wave-front data. Measurements were obtained for normal healthy subjects with ages ranging from 20 to 70 years. The magnitude of the RMS wave-front aberration (excluding defocus and astigmatism) of the eye increases more than threefold within the age range considered. However, the aberrations of the anterior corneal surface increase only slightly with age. In most of the younger subjects, total ocular aberrations are lower than corneal aberrations, while in the older subjects the reverse condition occurs. Astigmatism, coma, and spherical aberration of the cornea are larger than in the complete eye in younger subjects, whereas the contrary is true for the older subjects. The internal ocular surfaces compensate, at least in part, for the aberrations associated with the cornea in most younger subjects, but this compensation is not present in the older subjects. These results suggest that the degradation of the ocular optics with age can be explained largely by the loss of the balance between the aberrations of the corneal and the internal surfaces. PMID- 11778717 TI - Aging of the human lens: changes in lens shape upon accommodation and with accommodative loss. AB - Accommodation in the human eye occurs through controlled changes in crystalline lens shape, thickness, and refractive surface placement relative to the cornea. The changes in lens curvatures, whether surface or internal, have been characterized as a function of accommodation and subject age by use of quantitative analysis of Scheimpflug slit-lamp photographic images. Radii of curvature of the major lens refractive surfaces--the external and nuclear boundaries--decrease linearly with increasing accommodation in all eyes that are capable of accommodation. The rates at which they change with accommodation are age dependent, decreasing steadily toward zero with increased age. For the curves visible in each lens half, arising from boundaries between adjacent zones of discontinuity, radius of curvature and location are linearly related over the entire accommodative range for a given lens and over the age range for the population. The slope of this relationship changes with both accommodation and age, decreasing linearly in both cases. The relationship between these geometric changes and the loss of accommodative amplitude is discussed. PMID- 11778718 TI - Integrated light scattering as a function of wavelength in donor lenses. AB - The purpose of this work is to investigate the light-scattering properties of excised eye lenses with intact lens capsules--more specifically, to compare light scattering with light transmission at different wavelengths in aging and cataractous lenses. A lens is positioned at its focal-length distance from an optical fiber end and collimates the light from one of five laser lines (458-633 nm). By use of an integrating sphere with an extra circular port, the collimated directly transmitted light can be separated from the scattered light. For lenses with low light-scattering levels, integrated scattering showed a dependence on wavelength, but when light scattering increased the wavelength difference tended to level out. Despite the higher percentage of lens light scattering at lower wavelengths, when calculated as an "effective light scattering" (compensated for light transmission), more scattered light actually falls toward the retina at longer wavelengths. PMID- 11778719 TI - Structural modeling of contrast sensitivity in adulthood. AB - Structural equation modeling was used to assess the utility of the sensorineural model of contrast sensitivity proposed by Sekuler et al. [Vision Res. 24, 689 (1984)] to account for spatial vision in adulthood. In Study 1, visual acuity and contrast sensitivity (1.5-18 c/deg) were measured in 84 people between the ages of 19 and 81 yr. No three-filter model fitted the data well. Although a two filter model was associated with good fit indices, parameter estimates for both filters were inconsistent with physiological and behavioral data. In Study 2, acuity and contrast sensitivity (1.5-18 c/deg) were assessed in 95 observers between the ages of 23 and 73 yr. All measures were gathered once per month over a three-month period. The Sekuler et al. three-filter model did not fit the data from any time of measure, but a two-filter, bandpass model provided a consistent and excellent fit for all three waves. The model suggests that age-related change in the neural mechanisms underlying contrast sensitivity is minimal once acuity is controlled. Discrepancies between this conclusion and that reported by Sekuler et al. may be related to test type, psychophysical method, reliability, and sample selection. PMID- 11778720 TI - Age-related alterations in the diffusional transport of amino acids across the human Bruch's-choroid complex. AB - Photoreceptor maintenance is dependent on effective delivery of nutrients from the choroidal circulation by way of the acellular Bruch's membrane and the retinal pigment epithelium. Aging of Bruch's membrane is associated with thickening, increased cross linking of fibers, and deposition of debris culminating in reduced porosity. The present study has investigated the effects of aging on the diffusional transport of eight amino acids across Bruch's membrane in 19 human donors. Diffusion studies were carried out in Ussing chambers, and the amount of time-dependent transfer of amino acids across the preparation was quantified by reverse-phase high-performance liquid chromatography. Diffusion rates for all amino acids showed a significant linear decline with aging of donor. The importance of this reduction in delivery of amino acids is discussed with reference to both normal physiology and age-related macular degeneration. PMID- 11778721 TI - Decline of photopic multifocal electroretinogram responses with age is due primarily to preretinal optical factors. AB - Age-related changes in photopic retinal function were evaluated topographically with the multifocal electroretinogram (mfERG). Thirty-two subjects between the ages of 16 and 69 participated. There was a strong dependence on age for all mfERG response measures that was strongest for the group of central retinal responses (i.e., within 5 deg eccentricity) and approximately equal for responses between 5 and 20 deg. After adjustment for crystalline lens optical density and pupil diameter, significant effects of age were limited to central first-order (i.e., within 5 deg) and second-order response kernels. Simulation studies support an optical basis for the observed age-related changes. It is concluded that mfERG changes between the ages of 20 and 70 are due predominantly to preretinal optical factors. PMID- 11778723 TI - Optical diffraction in nonuniform cholesteric liquid crystals: phase-grating mode. AB - We have worked out the diffraction pattern in the phase-grating mode of a cholesteric liquid crystal (cholesteric) with a pitch gradient. The pitch gradients considered are symmetric and asymmetric with respect to the sample center. For a uniform input beam, the intensity profile of each diffraction order becomes broad. Further, in the symmetric gradient, the profile of each order is irregular, while in the asymmetric gradient it is nearly flat. For a Gaussian input beam, for the symmetrically deformed structure the profile for each order is asymmetric, while for the asymmetrically deformed structure, the profiles just becomes broad. We find that even a 5% nonuniformity in the pitch can drastically alter the diffraction profiles. PMID- 11778722 TI - Aging-related changes in the multifocal electroretinogram. AB - The multifocal electroretinogram (MERG) was recorded in the central 36 degrees diameter field in 26 young (19-30 yr) and 20 old (60-74 yr) adults in normal retinal health according to a fundus grading scale. The mean amplitude densities of the first-order and second-order responses in this retinal region were lower for old adults compared with young. The aging-related reduction of the first order amplitude density was greatest at the fovea and decreased as a function of eccentricity. Similarly, the amplitudes of the first negative and positive peaks of the first-order MERG waveform were reduced with age, and the pattern of reduction followed a similar eccentricity dependency. The aging-related changes in the MERG waveform may be due to slowed temporal adaptation in the aged retina. PMID- 11778724 TI - Effect of aging on multifocal oscillatory potentials. AB - Multifocal oscillatory potentials (m-OPs) are thought to reflect rod-cone interactions. We examined the effect of age on the topography of the m-OP responses out to an eccentricity of 30 deg. Fifty-eight normal subjects were studied, aged between 13.6 and 58.8 yr. The data show a linear decrease in amplitude and a linear increase in latency with age, which is significant for most potentials. The decrease is uniform over the retina. These results suggest that an age-related impairment is occurring at or before the inner retina. PMID- 11778725 TI - Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender. AB - We cross-sectionally examined the relationship between age, optic disc area, refraction, and gender and optic disc topography and retinal nerve fiber layer (RNFL) measurements, using optical imaging techniques. One eye from each of 155 Caucasian subjects (age range 23.0-80.8 y) without ocular pathology was included. Measurements were obtained by using the Heidelberg Retina Tomography (HRT), the GDx Nerve Fiber Analyzer, and the Optical Coherence Tomograph (OCT). The effects of age were small (R2 < 17%) and were limited to specific HRT, GDx, and OCT parameters. Disc area was significantly associated with most HRT parameters and isolated GDx and OCT parameters. Refraction and gender were not significantly associated with any optic disc or RNFL parameters. Although effects of age on the optic disc and RNFL are small, they should be considered in monitoring ocular disease. Optic disc area should be considered when cross-sectionally evaluating disc topography and, to a lesser extent, RNFL thickness. PMID- 11778726 TI - Senescent changes in parafoveal color appearance: saturation as a function of stimulus area. AB - The chromatic content (saturation) of monochromatic stimuli (480, 505, 577, and 650 nm) was scaled as a function of field size at three different retinal locations by 58 observers ranging from 18 to 83 yr of age. The different retinal locations (6 deg nasal, 2.5 deg inferior and 6 deg temporal eccentricity) were chosen according to anatomical studies demonstrating different degrees of senescent losses of cones or ganglion cells. Nine field sizes were tested, ranging from 0.0096 to 0.96 deg in diameter. The subjects used a percentage scale to judge the saturation of the flashed stimulus presentations (2 s on, 5 s off). The data analysis demonstrated that older observers require larger field sizes than younger observers to perceive hue as well as larger field sizes to reach the same level of scaled saturation. The spatial dependency of color appearance for younger and older observers was not correlated with senescent losses in retinal cells reported for the different retinal locations. The data were modeled by using an impulse-response function (i.e., Naka-Rushton equation) so that perceptive fields could be compared to electrophysiological measures of receptive fields or dendritic fields of retinal and cortical cells. PMID- 11778728 TI - Binocular contrast inhibition in subjects with age-related macular degeneration. AB - In subjects with normal vision, binocular contrast sensitivity is generally higher than monocular sensitivity, indicating summation of contrast in the two eyes. We have compared monocular and binocular contrast sensitivity and acuity for a group of 13 subjects with age-related macular degeneration (AMD). Relative to a normal control group, many of the AMD subjects showed reduced binocular contrast summation, and binocular inhibition was found for eight subjects for a narrow or an extended frequency band. A better monocular than binocular function may have practical implications for reading and orientation in AMD. PMID- 11778727 TI - Cone photopigment in older subjects: decreased optical density in early age related macular degeneration. AB - We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics. PMID- 11778729 TI - Characterization of optical diffraction gratings by use of a neural method. AB - Optical scatterometry by use of a neural network is now recognized as an efficient method for retrieving dimensions of gratings in semiconductors or glasses. For an on-line control, a small number of measurements and a rapid data treatment are needed. We demonstrate that these requirements can be met by combining data preprocessing and a proper neural learning method. A good accuracy is attainable with the measurement of only a few orders, even in the presence of experimental errors, with a reduction in learning and computing time. PMID- 11778730 TI - Staircase approximation validity for arbitrary-shaped gratings. AB - An electromagnetic study of the staircase approximation of arbitrary shaped gratings is conducted with three different grating theories. Numerical results on a deep aluminum sinusoidal grating show that the staircase approximation introduces sharp maxima in the local field map close to the edges of the profile. These maxima are especially pronounced in TM polarization and do not exist with the original sinusoidal profile. Their existence is not an algorithmic artifact, since they are found with different grating theories and numerical implementations. Since the number of the maxima increases with the number of the slices, a greater number of Fourier components is required to correctly represent the electromagnetic field, and thus a worsening of the convergence rate is observed. The study of the local field map provides an understanding of why methods that do not use the staircase approximation (e.g., the differential theory) converge faster than methods that use it. As a consequence, a 1% accuracy in the efficiencies of a deep sinusoidal metallic grating is obtained 30 times faster when the differential theory is used in comparison with the use of the rigorous coupled-wave theory. A theoretical analysis is proposed in the limit when the number of slices tends to infinity, which shows that even in that case the staircase approximation is not well suited to describe the real profile. PMID- 11778731 TI - Off-diagonal Mueller matrix elements in backscattering from highly diffusive media. AB - Measurements of a reduced Mueller matrix in backscattering from highly diffusive, dielectric samples are reported as a function of the angle of incidence. It was found that the off-diagonal terms depend greatly on the angle of incidence, increasing to a maximum near grazing incidence. We show that, despite a significant scattering originating in the bulk of such diffusive media, the nontrivial behavior of the off-diagonal Muller matrix is primarily due to surface scattering phenomena. The experimental data can be simply explained by assuming a random orientation of small particles and considering only double scattering in the plane of the surface. PMID- 11778732 TI - Ultrashort pulsed bessel beams and spatially induced group-velocity dispersion. AB - We find a new family of solutions of the nonparaxial wave equation that represents ultrashort pulsed light beam propagation in free space. The spatial and temporal parts of these pulsed beams are separable; the spatial transverse part is described by a Bessel function and remains unchanged during propagation, but the temporal profile can be arbitrary. Therefore the pulsed beam exhibits diffraction-free behavior with no transverse spreading, but the temporal part changes as if in a dispensive medium; the change is dominated by what we call spatially induced group-velocity dispersion. The analytical and numerical investigations show that the even- and odd-order spatially induced dispersions partially compensate for each other so as to give rise to pulse spreading, weakening, asymmetry, and center shift. PMID- 11778733 TI - Application of the parallel generalized projection algorithm to the control of two finite-resolution deformable mirrors for scintillation compensation. AB - A modification of the parallel generalized projection algorithm is presented that allows for the use of projections in a weighted norm. Convergence properties of the modified algorithm, denoted the weighted parallel generalized projection algorithm, are developed. The weighted parallel generalized projection algorithm is applied to the control of two finite-resolution deformable mirrors to compensate for both the amplitude and the phase fluctuations that result from propagation through a turbulent medium. Numerical results are shown that indicate that a two-deformable-mirror system can provide improved performance over that of a single-deformable-mirror system. PMID- 11778734 TI - Equivalence of cost generators for minimum cost flow phase unwrapping. AB - Phase unwrapping represents a crucial step in processing phase data obtained with techniques such as synthetic aperture radar interferometry, speckle interferometry, and magnetic resonance imaging. The so-called branch-cut approaches form an important class of phase unwrapping algorithms. In 1996, Costantini proposed to transform the problem of correctly placing branch cuts into a minimum cost flow problem [Proceedings of the Fringe '96 Workshop (European Space Agency, Munich, 1996), pp. 261-272]. The critical point of this new approach is to generate cost functions that have to represent all the a priori knowledge necessary for phase unwrapping. Any function transforming a priori knowledge into a cost function is called a cost generator. Several types of algorithms ranging from heuristic approaches to generators based on probability-theory interpretations were suggested. A problem arising from the growing diversity of algorithms is to find a criterion for the equivalence of different cost generators. Two cost generators are equivalent if they produce cost functions with the same minimal flow for every residue configuration on every image with all possible a priori knowledge. Comparing the results of different cost generators on test scenes can show only their non-equivalence. We solve this problem by proving the following mathematical classification theorem: Two cost generators are equivalent if and only if one can be transformed into the other by multiplication by a fixed constant. PMID- 11778735 TI - Analytical approximate solutions of the time-domain diffusion equation in layered slabs. AB - Time-domain analytical solutions of the diffusion equation for photon migration through highly scattering two- and three-layered slabs have been obtained. The effect of the refractive-index mismatch with the external medium is taken into account, and approximate boundary conditions at the interface between the diffusive layers have been considered. A Monte Carlo code for photon migration through a layered slab has also been developed. Comparisons with the results of Monte Carlo simulations showed that the analytical solutions correctly describe the mean path length followed by photons inside each diffusive layer and the shape of the temporal profile of received photons, while discrepancies are observed for the continuous-wave reflectance or transmittance. PMID- 11778736 TI - Alignment of optical delay lines for long-baseline stellar interferometry. AB - The problem of aligning an optical delay line for use in long-baseline stellar interferometry is discussed. particular, the development of the Navy Prototype Optical Interferometer alignment system is described. Rapid mirror alignment must be performed with sufficient precision that beam shear is limited to a few millimeters over an optical path length that may exceed 800 m. Two possible alignment algorithms are presented. The first is a null-seeking servo where the mirrors are adjusted to minimize the sum of their angular alignment errors. The second method utilizes a priori knowledge of the mirror separations to minimize the total shear. A number of time-dependent and time-independent errors that affect alignment and alignment stability are also discussed. PMID- 11778737 TI - Quantum-limited optical phase detection at the 10(-10)-rad level. AB - Interferometric detection of gravitational waves at a level of astrophysical interest is expected to require measurement of optical phase differences of < or = 10(-10) rad. A fundamental limit to the phase sensing is the statistics of photon detection--Poisson statistics for light in a coherent state. We have built a laboratory-scale interferometer to achieve and investigate the phase detection sensitivity required for the Laser Interferometer Gravitational-Wave Observatory. With 70 W of circulating power, we have obtained a phase sensitivity of 1.28 x 10(-10) rad/square root(Hz) at frequencies above 600 Hz, limited by quantum noise. Below 600 Hz, excess noise above the quantum limit is seen, and we present our investigations into the sources of this excess. Compared with the results of previous such experiments, the phase sensitivity over the full 100-Hz-10-kHz band of interest has been improved by factors of up to 100, with a factor-of-2.5 improvement in the quantum-limited level. PMID- 11778738 TI - Embryotoxicity of 1,2-dibromoethane in chick embryos in ovo: early and late effects. AB - Embryotoxic effects of 1,2-dibromoethane (DBE), a compound still widely used in industry, have been analyzed using chick embryos in ovo. Administration on embryonic days (ED) 3,4 or 5 induced dose-dependent embryotoxicity, manifested namely as the early embryonic death. A serious disturbance of the vascular system represented probably the main cause of strong embryolethality and growth retardation in the group of survivors. Amniotic bands in the parietal region and defects of brain and aorta prevailed in the malformation spectrum registered on ED 10. The local character of early induced changes suggests a direct effect of DBE itself in the embryotoxic action. This process is probably accomplished through interaction with lipids in cell membranes owing to the hydrophobic character of DBE molecules. The results, however, did not exclude an involvement of reactive metabolites in final embryotoxicity via the formation of DNA-adducts. In any case, a decreasing embryotoxicity of DBE with the age of treated embryos documented that the onset of liver function, assumed to occur on ED 5, did not increase the efficacy of DBE bioactivation. Our results confirmed the short-term embryotoxic properties of DBE reported in rat embryonic cultures. In addition, the in ovo system enabled us to reveal also long-term consequences represented namely by the formation of amniotic bands, not detectable in studies in vitro. The results obtained with the chick embryo in ovo confirmed the suitability of this system for embryotoxicity testing. PMID- 11778739 TI - Stereologic evaluation of the pig gastric wall and of somatostatinergic and serotoninergic immunoreactive mucosal cells during perinatal development. AB - A quantitative morphological study using stereologic methods was performed on vertical paraffin sections of the stomach of fetal and neonatal pigs. The sections were processed for 5-HT- and SOM-immunohistochemistry. In the neonatal pigs, the volume density of the submucosal layer in the pyloric gland region was approximately 15% less compared to the cardiac gland region. This suggests that altered functional demands after birth are temporarily related to and perhaps could promote the morphological diversification between the gastric regions. The distribution of 5-HT-IR and SOM-IR mucosal cells corresponds with previous observations in the adult mammalian stomach. However, based upon our results an age-dependent maturity or even different role is suspected for 5-HT and SOM. This is substantiated by the 4-fold rise of the volume occupied by 5-HT-IR mucosal cells in the pyloric gland region during development. Secondly, the regional differences of the volume density of SOM-IR mucosal cells vary according to developmental stage. The developmental variations of 5-HT- and SOM-IR mucosal cells contrast with findings in the rodent stomach. However, they are comparable to observations in man. PMID- 11778740 TI - Electronmicroscopical localization of nitric oxide synthase-containing nerve elements in cat pylorus. AB - Intrinsic nitric oxide synthase (NOS)-containing nerve cells and fibers were studied in the wall of the pylorus of cat at the ultrastructural level using ABC immunocytochemistry. Large numbers of NOS immunoreactive (IR) nerve cell bodies were observed in the myenteric and in the submucous plexuses, and few in the tunica propria mucosa. The NOS IR nerve fibers were most abundant in the inner circular muscle layer and in the tunica mucosa. They were found in very close vicinity to the smooth muscle cells of the inner circular muscular layer as well as to the blood vessels and the epithelial lining. The gap between the NOS IR nerve fibers and the membrane of the target cells was 20 to 250nm. Apparent synaptic contacts were observed between the IR nerve fibers and unlabelled nerve processes and other non IR nerve cell body. It is confirmed that NO might influence smooth muscle cell activity, regulate blood flow and modulate the function of the epithelial cells. Our ultrastructural study suggested that some of the NOS containing neurons belong to the intrinsic interneurons and have a regulatory effect on other intrinsic nerve elements involved in local neuronal reflexes. PMID- 11778741 TI - Differential expression of two carbohydrate epitopes, CD15 and HNK-1, in developing vertebrate olfactory receptor neurones. AB - According to the view of differentiation-related alterations in the glycosylation pattern of neurones, recent studies have shown development dependent expression patterns of lactoseries carbohydrate epitopes, CD15 and HNK-1, on olfactory receptor neurones in rats and chicks. In order to evaluate a general role for these epitopes during development of vertebrate olfactory receptor neurones, this investigation focuses on the situation in the mouse, bovine and Xenopus olfactory epithelium. In all three species CD15 expression was found on a subpopulation of morphologically mature receptor cells starting at the time of initial synaptogenesis. Whereas for bovine and Xenopus the timetable of HNK-1 expression is similar to that described for the chick, suggesting involvement in pathfinding, in the mouse HNK-1 is found on immature cells when mature CD15 positive receptor cells could already be discerned. By our results a role for CD15 during establishment of synaptic contacts and for HNK-1 during their formation is suggested. PMID- 11778742 TI - Pulsatile activity and hatching of in vitro produced cow blastocysts: effects of serum supplementation. AB - The effect of serum added to a modified SOF medium on pulsatile activity and hatching of in vitro produced cow blastocysts was investigated by time-lapse cinematography. Embryos were generated from abattoir material and cultured in mSOF without serum or with 10% FCS added at 42h pi. Addition of serum significantly increases pulsatile activity before zona rupture and reduces the time of hatching. Pulsatile activity does not seem to be involved in the hatching process. PMID- 11778743 TI - The relationship of handedness to asymmetry in the occlusal morphology of first permanent molars. AB - Handedness has been shown to be related to a number of systematic asymmetries in body dimensions, dermatoglyphic patterns and cerebral morphology. The aim here was to compare linear and angular tooth crown asymmetries of the permanent molars in healthy right-handed and left-handed subjects. The material comprised 27 children with recorded concordant left-side dominance of hand, eye and foot. The controls were an age- and sex-matched group with right side dominance. The material is based on the Collaborative Perinatal Project where detailed medical records and the dentitions, including accurate dental impressions, of over two thousand American children were examined in the USA in the sixties. Machine vision technique was used to obtain accurate three-dimensional information from the occlusal surfaces of the first permanent upper and lower molars. The directional asymmetry values of angular measurements of mandibular first molars showed evidence of asymmetry of opposite direction between the two examined groups. The results indicate that occlusal morphology of first permanent molars may be affected by handedness, and this tendency is most evident in the angular measurements of the mandibular molars. Fluctuating asymmetry did not differ significantly between the examined groups. PMID- 11778744 TI - Autoradiographic evidence for the sliding of the upper layer over the basement membrane in chicken blastoderms during gastrulation. AB - An upper layer (epiblast) fragment taken laterally from the Anlage fields of neural plate or chordamesoderm of a quail blastoderm, labelled with 3H glucosamine, was grafted isotopically (in a similar region), isochronically (at the similar stage of development) and isotropically (with the same caudocranial and dorsoventral polarity) in the epiblast of a mesoblast free area of a chicken blastoderm (St 4-5 Vakaet, 1970: full grown primitive streak). On the autoradiographs of the sections through such cultured blastoderms with fully integrated quail grafts, we observed a labelling of the basement membrane laterally and slightly cranially from the labelled graft in its final position. Since only the epiblast and its basement membrane are involved, the pattern of the observed labelling indicates that the grafted and integrated quail epiblast fragment glides in toto over the mediocaudally localized basement membrane, leaving behind a track of radioactivity. Sliding of whole groups of epiblast cells over the basement membrane seems thus to be a normal phenomenon during avian gastrulation. PMID- 11778745 TI - Immunohistochemical localization of large chondroitin sulphate proteoglycan in porcine gingival epithelia. AB - In this study, we report the immunohistochemical localization of versican in healthy porcine gingival epithelia. The monoclonal antibody (mAb), 5D5, specifically recognizes core proteins of large chondroitin sulphate proteoglycans such as versican, neurocan and brevican, but not the core protein of aggrecan. Because neurocan and brevican appear to be specific to nervous tissue, the large chondroitin sulphate proteoglycans examined in this study is most likely versican. In the keratinized layer of the attached gingival epithelium, the basal and spinous cell surfaces showed intense staining for mAb 5D5. In the parakeratinized layer of the sulcus epithelium, the localization was restricted to the basal and lower spinous layers. In the junctional epithelium, intense staining was observed in one or two cell layers near the enamel surface. Immunoelectron microscopy revealed high-density depositions of 5D5 immunoreactivity on epithelial cell surfaces. At the enamel surface, 5D5 immunoreactivity was localized to the dental cuticle of the junctional epithelium but was not present in the internal basal lamina. These results suggest that versican, a large chondroitin sulphate proteoglycan, is involved in epithelial differentiation and downgrowth. PMID- 11778746 TI - Introduction to endoscopic mucosal resection. AB - The advent of videoendoscopes showed the very minute details of the gastrointestinal tract. Three American and five Japanese endoscopists who are experts and founders in their original EMR for the entire gastrointestinal tract were invited. All of them have tremendous experience with EMR. One can appreciate the technique and pitfalls of EMR through their data analyses based on a large number of cases. In western countries, early esophageal cancers arising from Barrett's esophagus seem to be the most likely candidates for EMR. It is hoped that these techniques aid the reader's endoscopic practice and provide a better quality of life to patients. PMID- 11778747 TI - Endoscopic mucosal resection for mucosal cancer in the esophagus. AB - Endoscopic mucosal resection of the esophagus was found to be safe and easy to perform. Efforts must be made to detect early m1 to m2 cancers, which are indicated for EEMR. It is necessary to perform periodic endoscopic examination. During endoscopic examination, it is important to wash the inside of the esophagus with water and perform careful observation. Also, in high-risk patients and patients with abnormalities, such as erythema, turbidity, or hypervascularity, iodine staining should be performed frequently. Patients at high risk for esophageal cancer include (1) men more than 55 years old who are heavy smokers and drinkers; (2) patients with cancer of the head and neck region; and (3) individuals with a family history of cancer and those with achalasia, corrosive esophagitis, or Barrett's esophagus. PMID- 11778748 TI - Endoscopic mucosal resection for the entire gastrointestinal mucosal lesions. AB - In general, mucosal cancer of the gastrointestinal tract has the lowest risk of lymph node metastasis, and is curatively managed by the EMR procedure. PMID- 11778749 TI - Endoscopic mucosal resection of the esophagus: band ligation technique. AB - Endoscopic mucosal resection (EMR) is a minimally invasive endoscopic technique used in treating superficial cancers of premalignant lesions in the gastrointestinal tract. An attraction of this technique is that it can be curative with low morbidity, often providing the entire lesion for pathologic evaluation. The band ligation technique of EMR uses the existing technology of variceal band ligation to endoscopically place a band on flat mucosal lesions of the gastrointestinal tract to create a "pseudopolyp" before resection with an electrocautery snare. The band ligating technique and two variant band ligating devices are described. PMID- 11778750 TI - Widespread endoscopic mucosal resection. AB - The concept of widespread endoscopic mucosal resection is an alternative treatment for large surface area mucosal lesions. The need for such a technique is addressed by examining piecemeal mucosal resections. Early preclinical experience on esophageal widespread mucosectomy is presented. PMID- 11778751 TI - Endoscopic mucosal resection of the stomach: initial description. AB - A quantitative change of the enlargement of the biopsy specimen resulted in a qualitative change for endoscopy from only diagnosis to include therapy. This change of quality was also caused by another quantitative change of the size of detectable lesion, which was made smaller. PMID- 11778752 TI - Endoscopic mucosal resection using ligating device for early gastric cancer. AB - The advent of EMR made a major change in the strategy for early gastric cancer. Recently, many modified EMR techniques have been developed, such as using an endoscopic cap, a special tube, and so forth. We regard EMR-L as the first-line procedure because of its simplicity and ease, and it is hoped that all endoscopists will learn this procedure to improve the quality of life of patients who suffer from gastric cancer. PMID- 11778753 TI - Endoscopic mucosal resection of the colon: the Japanese technique. AB - Early colorectal neoplasms, especially flat-type and depressed-type lesions, should be treated with an EMR technique. In general because depressed-type lesions, in contrast to flat-type or protruded-type lesions, tend to invade the submucosa rapidly, they ought to be treated by EMR at an early stage. Histopathologically in the case of lesions that only minimally invade the submucosa without vessel invasion (sm1a and sm1b without vessel invasion), a treatment can be completed with EMR. Massive submucosal invasive cancers ought to be resected by surgical treatment because of the risk of recurrence or metastasis. In addition, pit pattern diagnosis with magnifying colonoscopy is useful to determine a therapeutic method for colonic neoplasms. Lesions with the type VN pit pattern represent malignancy and usually invade the submucosa massively, so it is better to treat them surgically from the outset. Endoscopic mucosal resection should be conducted under fully controlled endoscopy to prevent complications. EMR is a superior therapeutic method and will be performed frequently in the future. It is necessary for colonoscopists to determine a suitable therapy for each colorectal neoplastic lesion. They also need to master the EMR technique in the correct manner. PMID- 11778754 TI - Endoscopic mucosal resection of colon polyps. AB - The term submucosal injection polypectomy (SIP) more accurately describes the technique used for removal of flat colonic polyps and is preferred, in the colon, to endoscopic mucosal resection (a procedure that usually uses a special suction activated device). Using SIP, most polyps can be removed safely from any part of the colon. The methodology is described in detail and is within the capability of most colonoscopists. PMID- 11778755 TI - Perspectives in endoscopic mucosal resection. AB - The birth of endoscopic mucosal resection probably can be traced back to the early days of colonoscopy and polypectomy. With the advent of colonoscopy, endoscopists began encountering pedunculated and sessile mass lesions arising from the mucosal surface. The concept of snare polypectomy developed quickly, and this technique has become the standard of care in the management of colon polyps. Large sessile lesions, however, remain problematic, especially when they arise from the thin wall of the cecum and ascending colon. Serosal burns and frank perforations represent the most significant complication of this technique. PMID- 11778756 TI - Serum S100beta protein as a marker of disease activity in patients with malignant melanoma. AB - The purpose of the study was to evaluate serum S100beta protein as a marker of disease activity in patients with malignant melanoma (MM) and compare it with serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). One hundred sixty-four patients with MM, stages I-IV according to the American Joint Committee on Cancer (AJCC), were studied. Recurrent disease was categorized as active (AD) if metastases were evident clinically or with imaging investigations and inactive (ID) if no metastases were apparent at the time of sample collection. The sensitivity and specificity of S100beta, LDH, and ALP for discrimination between AD and ID were calculated using receiver-operating characteristic curve (ROC) analysis. Serum S100beta, LDH, and ALP concentrations were significantly higher in AD compared to ID. Serum S100beta protein was the best discriminator between AD and ID, the areas under the ROC curve being 0.89, 0.71, and 0.70 for S100beta, LDH, and ALP, respectively. Serum S100beta and LDH levels (both p < 0.0001) and serum ALP levels (p = 0.0014) corresponded with the number of metastatic sites involved. Using a cutoff point of 0.20 microg/L for serum S100beta protein, a specificity of 93% with a sensitivity of 68% was obtained for AD in MM. In stage IV disease, S100 was an independent predictor of survival in univariate (p = 0.001; hazard ratio = 1.0156) and multivariate (p = 0.038; hazard ratio = 1.0108) analyses. Serum S100beta protein is a better indicator of disease activity in MM than LDH or ALP and is an independent predictor of survival in stage IV disease. PMID- 11778757 TI - Treatment of the T98G glioblastoma cell line with antisense oligonucleotides directed toward mRNA encoding transforming growth factor-alpha and the epidermal growth factor receptor. AB - Antisense oligonucleotides (oligos) complementary to mRNA encoding transforming growth factor-alpha (TGF-alpha) and its target, the epidermal growth factor receptor (EGFR), are efficacious against human prostate and breast cancers carried in athymic nude mice. Glioblastomas, also regulated by EGFR expression, would appear to be similarly susceptible, and we now employ them against the T98G tumor model. T98G cells were distributed into wells and allowed to adhere prior to addition of oligos (12.5 microM) directed against TGF-alpha and/or EGFR for 6 d of treatment before thymidine radiolabeling. Supplemental media and oligos (25 microM final concentration) were added after d 3. Statistically significant inhibition by oligos directed against TGF-alpha, EGFR, and their combination was 13.8%, 26.3%, and 18.1%, respectively. In a subsequent experiment cells were incubated with increasing amounts of each oligo and their combination for 3 d prior to radiolabeling. Statistically significant inhibition of growth for either oligo at every concentration was found. Cells incubated with 6.25, 12.5, 25, and 50 microM antisense directed against TGF-alpha had a mean inhibition of 29.3%, 33.3%, 21.7%, and 46.6%, respectively. Cells similarly treated with oligos against EGFR had a mean inhibition of 77.9%, 80.3%, 82.0%, and 83.7%, respectively, and cells incubated with 6.25, 12.5, 25 and 50 microM of each oligo had a mean inhibition of 74.7%, 70.6%, 70.8%, and 76.3%, respectively. Lastly, in a paired experiment, cells treated with 0, 0.39, 0.78, 1.56, 3.125, and 6.25 microM of oligos, either specifically directed against EGFR or a random control, for 3 d were evaluated for both thymidine incorporation and EGFR expression. Statistically significant inhibition of 3H-thymidine incorporation was seen in cells with the oligo specifically directed against EGFR at 3.125 microM and 6.25 microM when compared to non-oligo containing controls. This was accompanied by a comparable significantly decreased expression of a low-MW reactive derivative of EGFR at 3.125 microM and 6.25 microM in Western blots, and of a high-MW reactive EGFR at 6.25 microM. The significant effect against high-MW EGFR was observed vs both the non-oligo containing control and the random sequence. Oligo concentrations between 0.78 and 1.5 microM also resulted in decreased expression of the low-MW form, but not significant differences in thymidine radiolabeling. In recovery experiments, cells treated initially with greater oligo concentrations required significantly increased time to recover, particularly in cells treated with EGFR directed oligos. Intracellular uptake and nuclear localization was demonstrated with FITC tagged oligos. In summary, even at relatively low oligo concentrations and short exposure, oligos against TGF-alpha, and particularly EGFR, significantly inhibit in vitro growth of the T98G glioblastoma, possibly mediated by decreased EGFR expression. PMID- 11778758 TI - Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis: a pilot study with ACTH-Depot plus tropisetron. AB - The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as < or = 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial. PMID- 11778759 TI - Reproducibility of tumor response evaluation in patients with high-grade malignant non-Hodgkin's lymphoma. AB - Estimation of complete response (CR) and partial response (PR) in patients with non-Hodgkin's lymphoma (NHL) is associated with a number of potential sources of error. The aim of this study was to define the reproducibility of response evaluation performed by an independent review committee (RC). In a phase III study of patients >60 yr with aggressive NHL, 60 patients who were already evaluated by the independent review committee (RC 1) for response were randomized to three groups and re-evaluated (RC 2). The assessment was classified into one of seven mutually exclusive categories, where the important borderlines with regard to one of the major end-points of the study, the CR rate, were between CR, "CR uncertain" (CR(U)), and PR. A discrepancy between RC 1 and 2 was found in 8/60 patients (13.3%), influencing the CR/CR(U) status in four of these patients. Two CR and two PR patients were reclassified as CR(U). Thus, CR/CR(U) was changed in 4/60 (6.7%). The reports of the local investigators were compared with that of RC 1 in 254 patients. The CR/CR(U) status was affected in 41 of these patients (16.1%). It is concluded that an independent RC is a major prerequisite for a uniform response evaluation in phase III clinical trials. However, the good RC reproducibility does not motivate a second assessment. Moreover, in the phase III setting end-points other than the CR rate, such as time to treatment failure, cause specific and overall survival are preferred. PMID- 11778760 TI - Rituximab (Mabthera, Rituxan) in patients with recurrent indolent lymphoma: evaluation of safety and efficacy in a multicenter study. AB - The objective of this multiinstitutional study was to evaluate the safety and efficacy of rituximab at standard four weekly doses in patients with recurrent indolent lymphoma. Thirty-eight patients entered into this study, 63% had follicular lymphoma and 61% had an IPI score of 2 or more. Median disease duration was 3 yr, median number of prior treatments was three, and 66% of patients responded to the immediate past treatment with a median remission duration of 3 mo. A total of 158 antibody doses were given, including two patients who received two courses of four infusions each. One patient developed acute respiratory failure after the second dose and required assisted ventilation. There was no immediate relationship to the antibody infusion and no evidence of infection. This complication resolved and the patient successfully completed the full course of the antibody treatment. Another patient discontinued therapy after the second dose owing to intolerable fever and painful erythema. Sixty percent of the first, and 20% of subsequent rituximab infusions were associated with infusion-related reactions including mild fever, chills, and occasional skin eruptions. Complete and partial responses were achieved in 24% and 35% of 34 evaluable patients, respectively, for an overall response rate of 59%. The median time to progression/relapse in responding patients was 16 mo (95% CI, 6.4, 25.6) compared with a median of 3 mo duration of response to the immediate previous therapy in these patients. Longer response duration post rituximab monotherapy than with previous treatment in this series of heavily pretreated patients suggests a major role for the antibody in the therapy of patients with indolent lymphoma. PMID- 11778761 TI - Tumor lysis syndrome in small cell lung cancer. AB - Tumor lysis syndrome, resulting from the abrupt release of intracellular ions into the blood stream due to sudden tumor cell death, is a serious complication of chemotherapy treatment. This syndrome occurs more frequently in hematologic malignancies and lymphomas. Its incidence in solid tumors is rare, but has a high mortality rate owing to the lack of prophylactic therapy to prevent this complication. We report a case of tumor lysis syndrome accompanied by death in a patient with extensive stage small cell lung cancer who was treated with cisplatin and etoposide, and review the risk factors associated with the syndrome in solid tumor patients who are likely to respond to chemotherapy. PMID- 11778762 TI - Bilateral chylothorax due to retrosternal goiter in a patient with non-Hodgkin's lymphoma. AB - Chylous pleural effusion, or chylothorax, usually results from obstruction to or disruption of the thoracic duct. Malignant etiologies are the most common cause of chylothorax, lymphoma accounting for the majority of non-traumatic chylous effusions. We report an unusual case of bilateral chylothorax associated with a retrosternal toxic multinodular goiter in a patient with non-Hodgkin's lymphoma. An ablative dose of 131I was administered with apparent initial clinical improvement. The pathogenesis of chylothorax and therapeutic considerations are discussed. PMID- 11778763 TI - Metastases in small thickness oral squamous-cell carcinoma arising in oral lichen planus. AB - Oral lichen planus (OLP) is classified among precancerous conditions, as it is considered a generalized state associated with a significantly increased risk of cancer. The objective of this study was to discuss ultra-structural aspects of OLP that could play a role in enhancing metastatic potential, thus worsening the prognosis in oral squamous-cell carcinoma (OSCC). We report four cases of microinvasive OSCC which have occurred in OLP patients. All of them were stage I tumors, with a mean thickness of 1.75 mm. Recent studies indicate a tumor thickness over 4 mm as predictive of nodal metastases, but within 6 mo, our four patients with OSCC arising from OLP developed lymphnodal metastases. Our findings suggest that OLP-related OSCC may have a worse prognosis because of increased metastatic potential; obviously, further investigation is required, but this preliminary evidence emphasizes that extremely careful management of OLP patients is mandatory, and in cases of OSCC arising from OLP, a more radical treatment is probably required. PMID- 11778764 TI - Choriocarcinoma of the gallbladder: treated with cisplatin-based chemotherapy. AB - A case of non-gestational choriocarcinoma, primary in the gallbladder, is described. Pathology showed a mixture of adenocarcinoma and choriocarcinoma. A Medline search for the last 10 years has shown no similar cases reported. The use of cisplatin-based chemotherapy to treat non-gestational choriocarcinoma has also not been described. This patient showed a rapidly progressive disease as described in other reported cases of non-gestational choriocarcinoma. However, cisplatin-based chemotherapy, in this patient, produced a partial response defined as significantly decreased beta-HCG titers (more than 50%), and with stable appearance or slightly improvement of hepatic metastasis and survival for 1 yr. PMID- 11778766 TI - Stress as a diagnostic challenge for postconcussive symptoms: sequelae of mild traumatic brain injury or physiological stress response. AB - There is considerable controversy regarding whether persistent postconcussive symptoms (PCS) are injury-specific, in a subgroup of individuals after mild traumatic brain injury (TBI). The following findings have contributed to this controversy: (1) The base rate of PCS in mild TBI is comparable to uninjured controls; and (2) The severity of PCS covary with daily stress levels (Gouvier, Cubic, Jones, Brantley, & Cutlip, 1992). We examined this relationship further by evaluating the effects of experimental conditions of stress or relaxation on individuals with TBI and uninjured control subjects, with low and high PCS endorsement. We evaluated psychophysiological parameters, neuropsychological performance, and changes in PCS and stress perception. In our study, subjects with TBI increased PCS after engaging in cognitively challenging tasks, and demonstrated significant autonomic changes in the stress condition. Symptomatic TBI subjects exposed to high stress had increases in PCS complaints, decreased speed of information processing, and subtle memory deficits. Our results suggest that PCS are injury-specific and that individuals with a history of TBI are susceptible to the effects of stress. Relaxation training including breathing retraining may be an effective means of decreasing PCS and cognitive complaints in subjects with mild TBI. PMID- 11778765 TI - Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. AB - Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. The median duration of response is 9-12 mo. Because of the antibody's higher activity on circulating lymphocytes, it has been used for in vivo purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF) alpha and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders. PMID- 11778767 TI - Impact of musical experience on the Seashore Rhythm Test. AB - The Seashore Rhythm Test (SRT) is sensitive to musical talent. The possibility that this reduces its clinical sensitivity in cognitively impaired persons with musical experience was investigated. Subjects were 101 referrals to the neuropsychology service of a large medical center. The results indicate that patients with a substantial amount of musical experience tend to perform normally on the SRT, even when overall performance on a neuropsychological test battery suggests cognitive impairment. This finding suggests caution in interpreting normal SRT results in those with a musical background. PMID- 11778768 TI - The effect of differing scoring methods for the Tower of London task on developmental patterns of performance. AB - The Tower of London (TOL) task is frequently used to assess executive functioning in both adults and children, although there remains considerable controversy over what it measures and how to score it. In this study we compare two scoring methods and find that correlations between them were high for 7-year-olds (.86), and dropped to a low of .47 for adults. These results demonstrate that the TOL necessarily has different construct validity in adults and children. Second, results of one method (based on errors only) show a developmental trend in performance from middle childhood to adulthood, while the other (based on errors and time) shows a developmental progression from ages 7 to 13, but not between 13 year-olds and young adults. Thus, scoring method influences the resulting developmental model. PMID- 11778769 TI - Ecological validity of neuropsychological and personality measures of executive functions. AB - Associations between two types of measures of executive functions, namely, neuropsychological and personality, and measures of real-world behavior were investigated. Undergraduate students were administered neuropsychological measures of executive functions and completed a personality questionnaire developed to measure traits central to the construct of executive functions. Participants also reported on their behavior. Hierarchical regressions indicated that neuropsychological and personality measures of executive functions were significant predictors of different types of behavior. Neuropsychological measures predicted work behaviors and personality measures predicted substance use, risk-taking, and aggressive behaviors. Findings highlight the importance of including personality assessment in standard neuropsychological assessment in order to maximize ability to predict real-world behaviors relevant to independent and socially responsible functioning. PMID- 11778770 TI - Older adult norms for the Southern California Figure-Ground Visual Perception Test. AB - Older adult norms for men are provided for the Southern California Figure-Ground Visual Perception Test (FG; Ayres, 1966), based on the performance of 117 patients from a geriatric medicine and rehabilitation facility ranging in age from 40 to 77 years. Reasons are presented for administering the entire test rather than using the traditional cutoff. When comparing FG performance to norms of younger adults (Bieliauskas, Newberry, & Gerstenberger, 1988), results indicate that figure-ground discrimination is poorer in older individuals. The norms provided here serve to complement the previous study employing FG, and it is hoped that they will encourage its wider use. PMID- 11778771 TI - Short cognitive/neuropsychological test battery for first-tier fitness-to-drive assessment of older adults. AB - Since fitness-to-drive evaluation of elderly drivers has become an important issue, we developed a short first-tier screening battery to evaluate the necessity for further referral to specialised centres. Our sample consisted of 84 subjects between 65 and 96 years who came to the Belgian Road Safety institute for a fitness-to-drive evaluation. Using cross-validated discriminant analyses, the predictive power of a battery consisting of the Trail Making Test, Part A, a visual acuity test, a clock drawing test, the Mini-Mental State Examination (MMSE) and age was analysed. The judgement by an independent driver instructor (fit-to-drive vs. not unconditional fit-to-drive), based on a real world road test was used as the dependent variable. Classification functions based on the significant discriminant function yielded a specificity score of 85% (subjects fit-to-drive correctly classified) and a sensitivity score of 80% (subjects as not unconditional fit-to-drive correctly classified). These results highlight the potential value of a short screening instrument that can be used in primary health care settings. This instrument may be useful as a first step in a multi tier assessment procedure. PMID- 11778772 TI - Comparability of the Rey and Mack forms of the Complex Figure Test. AB - Equivalent versions of the Complex Figure Test (CFT) are useful for assessing change over time in constructional skills, planning, spatial organization, and visual-spatial memory while minimizing practice effects. To address the need for an equivalent version of the CFT to the Rey, the present study compared copy and 45 min-delayed recall accuracy scores of the Rey and Mack CFTs obtained from 245 adults involved in a study of the neuropsychological correlates of sleep apnea and its treatment. Accuracy scores did not significantly differ between individuals with and without sleep apnea. Also, there was no significant difference between copy or recall accuracy scores obtained on the Rey and Mack CFTs. Similar correlations were found between relevant demographic factors, estimated IQ, and accuracy scores for both CFTs. These data suggest that the Mack figure may be a useful alternative to the Rey CFT. PMID- 11778773 TI - Sources of poor performance on the Rey-Osterrieth Complex Figure Test among children with learning difficulties: a dynamic assessment approach. AB - A dynamic assessment approach was used to examine the source of poor performance on the Rey-Osterrieth Complex Figure Test (ROCF) among 202 school-age children referred for learning difficulties. The ROCF was administered in the standard format and then in a structured format that highlighted the design's organizational framework. Manipulating encoding in this way improved recall to at least age-level for the majority of children. Those children who did not benefit from the structured format had relatively poor visual organizational skills. For most children with learning problems, poor ROCF performance stems from metacognitive difficulties; for a minority, the source appears to be more perceptual. A dynamic assessment procedure can enhance the diagnostic utility of the ROCF for children. PMID- 11778774 TI - Metamemory and tested cognitive functioning in multiple sclerosis. AB - Metamemory, or one's knowledge and self-report of memory ability, has been researched extensively; however, few studies have examined it in multiple sclerosis (MS). Because impairment in cognitive domains besides memory may affect memory functioning, patients may self-report problems with memory that are indicative of impairment in cognitive domains besides memory. One goal of the current study was to test this hypothesis in MS. A group of 55 MS patients were administered a variety of cognitive tasks and a self-report metamemory measure; patients' significant others were also given a metamemory measure requiring them to rate patients' memory abilities. Results indicated that patients' metamemory reports were significantly (p < .05) correlated with verbal recall, attentional, and executive tasks. Significant other ratings of patients' metamemory were correlated with verbal recall and attentional measures. Stepwise regression analyses including all relevant cognitive and demographic variables indicated that only education and Symbol Digit accounted for significant independent variance in patients' current memory reports. Our results suggest: (1) subjective complaints of memory difficulties by MS patients reflect difficulty in cognitive domains besides memory, (2) MS patient self-reports of memory difficulty are at least as accurate as significant other reports, and (3) patients with more education are more accurate in their metamemory ratings. These findings have implications not only for a better understanding of metamemory in MS, but also for more effective treatment and rehabilitation of MS patients. PMID- 11778775 TI - Complex real-world functioning and neuropsychological test performance in older adults. AB - In stepwise regression analyses with Independent Living Scales (ILS) summary and subscale scores as the dependent variables, 8 of 10 psychometric measures from our battery for older adults emerged as important predictors for 69 patients referred for clinical assessment. The Dementia Rating Scale (DRS) score entered first for 6/8 analyses. However, measures of confrontation naming, oral reading, verbal fluency, paragraph recall, visual perception, complex attention, and depression also added explanatory power. Multiple Rs ranged from .66 to .88 except for the Social Adjustment subscale, which correlated only with the depression scale. PMID- 11778776 TI - Treating missing data in a clinical neuropsychological dataset--data imputation. AB - Missing data frequently reduce the applicability of clinically collected data in research requiring multivariate statistics. In data imputation, missing values are replaced by predicted values obtained from models based on auxiliary information. Our aim was to complete a clinical child neuropsychological data set containing 5.2% of missing observations. This was to be used in research requiring multivariate statistics. We compared four data imputation methods by artificially deleting some data. A real-donor imputation method which preserved the parameter estimates and which predicted the observed values with acceptable accuracy was used to complete the data set. In addressing the lack of studies with regard to treatment of missing data in neuropsychological data sets, this study presents information on the outcomes of applying data imputation methods to such data. The imputation modeling described can be applied to a variety of clinical neuropsychological data sets. PMID- 11778777 TI - Malingering disorientation to time, personal information, and place in mild head injured litigants. AB - Suchy and Sweet (2000) found disorientation in 12 (24%) of 50 benefit-seeking patients. They suggested that this level of disorientation, particularly in a sample that should not experience disorientation, is comparable to published base rate studies of malingering. The present study examined disorientation to date and personal information/place as indicators of malingering following a mild head injury. A mild head injury group (MHIG) in litigation was compared to patient groups with diagnoses of a psychiatric condition, Alzheimer's disease, vascular dementia and moderate to severe closed head injury group not in litigation. In the MHIG, disorientation to date and personal information/place was present in 7.4 and 5.7% of the sample, respectively, and significantly less than that found in the other three neurological groups. Disorientation to date was more common in the MHIG when compared to the psychiatric controls, but not disorientation to personal information/place. Relying on disorientation as an indicator of malingering, at least for mild head injured litigants, may underestimate its prevalence. PMID- 11778778 TI - Efficacy of the full and abbreviated forms of the Portland Digit Recognition Test: vulnerability to coaching. AB - The present study compared the efficacy of the abbreviated and the full scale PDRT in simulated malingerers and effortful controls. A total of 80 undergraduates were randomly assigned to normal effort, naive simulators, informed simulators, and simulators with information and warning about malingering detection groups. Comparison shows abbreviated forms are superior to the full scale PDRT at detecting malingerers. The conservative abbreviated form detected 80% of the Naive and Informed malingerers and 35% of the Warned. Warned Simulators were overall better at avoiding detection than Naive or Informed Simulators. PMID- 11778779 TI - Performance on the Test of Everyday Attention and standard tests of attention following severe traumatic brain injury. AB - The Test of Everyday Attention (TEA) was designed to address some of the limitations of established measures of attention. However, very few studies have examined its clinical utility. A group of 35 patients who had sustained a severe TBI were compared with 35 age- and education-matched controls on the TEA, Stroop, SDMT, WMS-R Digit Span, Ruff 2s and 7s Selective Attention Test, and PASAT. Of the TEA subtests, only the Map and Telephone Search subtests of the TEA produced significant differences between the two groups, suggesting a deficit in visual selective attention following TBI. Principal components analysis revealed a four component / factor structure of attention, largely consistent with previous studies. A logistic regression found that the TEA Map Search and Modified Colour Word subtest of the Stroop were best able to discriminate between the TBI and control groups. When the TBI group was divided into Early ( < 1 year post injury) and Late ( > 2 years post injury) groups, there was an additional deficit on the Lottery (sustained attention) subtest in the Early TBI group, indicating that there is some recovery in attentional function beyond 1 year post injury. PMID- 11778780 TI - Toward an explanation of Dodrill's observation: high neuropsychological test performance does not accompany high IQs. AB - Dodrill demonstrated that many neuropsychological tests correlate poorly with intelligence in the above-average intelligence range, while correlating adequately throughout the total range. The most parsimonious explanation for this observation is that most neuropsychological tests have a low ceiling with a constricted range at their upper limits precluding the possibility of high correlations. This explanation is examined through various examples. Interpretation should take this constricted range into consideration for people with above-average premorbid ability, by supplementing neuropsychological tests with intellectual ability tests. Also, the future construction of neuropsychological tests should extend the upper range. PMID- 11778782 TI - Gastrointestinal infectious disease complications following transplantation and their differentiation from immunosuppressant-induced gastrointestinal toxicities. AB - It is often very difficult to distinguish between infection-related and immunosuppression-related gastrointestinal (GI) complications after transplantation. The risk of infection itself is determined by the patient's net state of immunosuppression as well as the presence of anatomic or technical abnormalities and the patient's epidemiological exposures. Of the anatomic abnormalities, diverticulitis is a particular problem in transplant patients, with a high rate of perforation and abscess formation. The causes of infectious disease syndromes are very different immediately after, early after, and late after transplantation. Infection during the first month may result from a pre existing infection in the donor or recipient, or from the surgical wound, endotracheal tube, vascular access or drainage. During 1-6 months after transplantation, viruses attack and, with sustained immunosuppression, make opportunistic infections possible. Beyond 6 months after transplantation, the 80% of patients with good result from the transplant are at risk primarily for community-acquired microbes, including such enteric pathogens as Salmonella. Of the remaining patients, 10% have chronic viral infections and the 10% who have poor allograft function are at greatest risk for opportunistic infection. This time line is helpful in determining whether a GI complication is likely to be related to infection rather than a specific effect of an immunosuppressant drug. Fever, inflammatory cells in the stool, abnormalities on endoscopy or computed tomography and leukocytosis can be useful in the diagnosis but are inconsistent markers for an infectious cause. PMID- 11778783 TI - The pathophysiology of diarrhea. AB - Diarrhea is a very common event after transplantation, but its cause may be difficult to identify. The first step in determining the cause in any particular case is an understanding of the etiology of diarrhea in general. Although diarrhea often is categorized into such types as secretory versus osmotic, or electrolyte transport-related versus motility-related, a thorough understanding of the problem requires knowledge of how the paracrine, immune, nervous and endocrine systems react to each other as well as to infection, drugs or other stimuli. PMID- 11778784 TI - Immunosuppressive therapy and post-transplantation diarrhea. AB - Gastrointestinal complications, including diarrhea, are among the anticipated adverse events secondary to immunosuppression. The reported overall rate of diarrhea may be affected by drug-specific effects, dose-response effects, interactions with other medications, drug formulation, the length of study follow up, reporting bias and population characteristics such as ethnicity and baseline disease, including transplant organ type. The true incidence of diarrhea is often difficult to assess from the numerous published clinical trials. A number of deficiencies, including self-reporting, interstudy comparisons, lack of blinding, concomitant medications and a general lack of standardization and quantification of diarrhea may greatly obscure comparisons among the different immunosuppressive medications. This review considers each of these factors in assessing the overall incidence of post-transplantation diarrhea for the various immunosuppressive medications currently in use. PMID- 11778785 TI - Prophylaxis and treatment of gastrointestinal complications following transplantation. AB - Most transplant recipients will experience some type of gastrointestinal (GI) complication. These effects often are caused by infectious damage induced by a variety of opportunistic organisms, but they also may be due to mechanical injury during surgery or to metabolic or organ toxicity associated with immunosuppressive regimens. Although some of these GI complications can substantially impair quality of life or even carry significant mortality risk, many of them can be prevented, and most of them can be treated medically without the need to stop immunosuppression and expose the patient to the risk of rejection. Limiting the use of steroids, giving prophylactic antiviral and antifungal agents (particularly to patients at risk) and adopting a low threshold for endoscopy are among the most important measures that can be used to avoid GI complications after transplantation. PMID- 11778786 TI - Exhaled carbon monoxide in patients with lower respiratory tract infection. AB - The concentration of carbon monoxide (CO) in exhaled air is increased in patients with asthma, bronchiectasis and upper respiratory tract viral infections. However there is no information about the level of CO in patients with lower respiratory tract infection. We studied a group of 35 patients (22 males) aged 45 +/- 3 (SEM) years with cough productive of purulent phlegm and pyrexia in a general practice setting. All were non-smokers or ex-smokers and none had a previous history of respiratory problems or diabetes. We measured CO level in exhaled air before and after a course of antibiotics. Therapy was deemed successful when patient no longer complained of cough productive of purulent phlegm. Twenty-eight of 35 patients had elevated CO level at their initial visit. Twenty-two out of 35 patients reported clinical improvement after antibiotic treatment and this was associated with a fall in exhaled CO level from 5.2 +/- 0.5 ppm to 2.3 +/- 0.3 ppm (P < 0.0001). We suggest that simple CO measurements in exhaled air can detect the inflammatory process within the airways caused by infection and that a repeat measurement can be used to assess the nature of inflammation. PMID- 11778787 TI - Using a revised asthma morbidity index to identify varying patterns of morbidity in U.K. general practices. AB - Both in terms of morbidity and mortality, the therapeutic and organizational management of asthma pose a considerable and continuing challenge to healthcare delivery. One element in attempts to meet this challenge is the recognition of appropriate outcome measures to assess progress in tackling the burden of this disease. This study therefore aimed to assess pragmatically the effectiveness of a revised asthma morbidity index in identifying varying patterns of morbidity in U.K. general practices. A postal survey was conducted of 2,762 patients believed to have or have had asthma from the lists of 12 general practices within the Eden Valley in Cumbria, using a questionnaire which combined the revised Jones morbidity index with questions on age, medication and perception of current asthma. Prescribing data were also recovered for 11 of the practices for the quarter within which the postal survey was conducted. Responses were obtained from 2,123 subjects (77%), of whom 1,474 (70%) believed themselves to be currently asthmatic. In this group, 18% reported low morbidity 34% medium morbidity and 48% high morbidity Age and inhaled steroid use were both positively and significantly associated with high morbidity. Those taking inhaled steroids were 1.4 times more likely to report high morbidity than those nottaking steroids. The prescribed corticosteroid/bronchodilator ratio for cost was both negatively and significantly associated with high morbidity. The revised morbidity index is a simple tool of use in the surveillance of asthma in primary care. It identifies spectra of morbidity which vary between practices, which may be of use in assessing the quality of asthma care provided in the community. PMID- 11778788 TI - Combined inhalation of nitric oxide and oxygen in patients with moderate to severe COPD: effect on blood gases. AB - Inhaled nitric oxide (NO) has been reported to improve oxygenation in patients with COPD if administered in combination with oxygen (O2). Little, however, is known about the variability of these effects and the potential influence of body position. Twenty-six spontaneously breathing patients with moderate to severe COPD inhaled clean air, O2(FiO2, 0.29), 5 ppm NO, 5 ppm NO+O2, 10 ppm NO+O2, 10 ppm NO, and again clean air in an upright position. Blood gas analysis from arterialized capillary blood was performed after each inhalation. Tests were repeated on different days to assess the variability of the response. Furthermore, eight patients were studied in both upright and supine position while inhaling 5 ppm NO in the presence or absence supplemental O2. As compared to clean air, NO led to a mean decrease in PaO2 of -0.9 mmHg at 5 ppm and of -2.8 mmHg at 10 ppm NO. Similarly, NO+O2 led to a dose-dependent fall in PaO2 of -1.8 and -3.6 mmHg, respectively, as compared to O2. Average within-subject variation (SD) of the effects elicited by 5 and 10 ppm NO was 2.4 and 2.3 mmHg without additional O2, and 4.7and 5.3 mmHg with O2. The effects of 5 ppm NO+O2 differed significantly between upright and supine position; as compared to O2 alone, mean (SD) changes were -3.7 +/- 5-8 vs. +1.1 +/- 4.9 mmHg, respectively. Our findings suggest thatthe addition of NO to inhaled oxygen, when given in an upright position, does not lead to an improvement of PaO2 in patients with moderate to severe COPD. Furthermore, it turned out that it was not possible to define responders and non-responders to inhaled NO on an individual basis, since the variability ofthe responses was similar to the mean PMID- 11778789 TI - Infection of TT virus in patients with idiopathic pulmonary fibrosis. AB - The precipitating factors of idiopathic pulmonary fibrosis (IPF) have not been elucidated. Recently, a novel DNA virus named TTvirus (TTV) was discovered in a patient with post-transfusion hepatitis of unknown aetiology TTV is a circular, single-stranded DNA virus of 3.8 kB. To evaluate the relationship between TTV and IPF, the sera of 33 patients with IPF were tested for the presence of TTV DNA by semi-nested polymerase chain reaction. TTV DNA was detected in 12 (36.4%) IPF patients. The serum lactate dehydrogenase (LDH) level was significantly higher in the IPF patients withTTV than in those without TTV (802 +/- 121 vs. 530 +/- 49 IU l(-1), p < 0.05). Six (50%) of 12 patients in theTTV DNA-positive group died during the observation period, while only six (28.6%) of 21 patients in theTTV DNA-negative group died. The 3-year-survival rate was significantly lower in the TTV DNA-positive group than in theTTV DNA-negative group (58-3% vs. 95.2%, P <0 02). Replicative intermediate forms of TTV DNA were detected in the lung specimen from a TTV-infected IPF patient. TTV infection influences the disease activityand prognosis of IPF in some cases. Further studies are required to elucidate the clinical significance of TTV in IPF. PMID- 11778790 TI - Three-year follow-up study of allergy in workers in a mushroom factory. AB - Exposure to mushroom spores may cause many respiratory allergic diseases, however, there has been no serial study in a mushroom factory to address this problem. The aim of this study was to investigate the serial changes in respiratory allergy and the incidence of hypersensitivity pneumonitis (HP) in mushroom workers. A 3-year follow-up study, beginning in June 1996, was conducted in a newly operating mushroom factory in which one kind of mushroom is produced: Hypsizigus marmoreus (Bunashimeji). Allergic symptoms, chest roentgenogram, serum precipitins to the spores and soluble adhesion molecules in sera were evaluated once a year in 60 workers and 20 controls. Three out of the 60 subjects were diagnosed as having HP caused by inhalation ofthe mushroom spore and they were therefore excluded from this study, and the 57 non-HP subjects were evaluated. In this study 24 workers quit because of intolerable cough, runny nose, wheezing, sputum, fever elevation and/or shortness of breath at their place of work. During each year of this study as many as 70-80% of employees suffered some ofthe above symptoms, cough being the most frequent, and positive rate of serum precipitins to the spore revealed 30% in 1996, 93% in 1997 and 94% in 1998. From the June 1996 examination until the following May, serum soluble intercellular adhesion molecule-1 levels of the 15 workers who quit during that period were significantly higher than those in the 42 workers still employed in 1997 (P < 0.05). Workers in Bunashimeji mushroom factories might be at critical risk of developing respiratory allergy. In our 3-year study over 90% workers were sensitized to the spore, 40% quit because of the symptoms and 5% developed HP. It was suggested that workers should be counselled about the risk of mushroom allergy and precautionary measures should be taken to prevent its occurrence. PMID- 11778791 TI - The efficacy of a new salbutamol metered-dose powder inhaler in comparison with two other inhaler devices. AB - An open cross-over and randomized study was carried out in order to compare the efficacy and safety of inhaled salbutamol delivered from a new 50 microg dose(-1) metered-dose dry powder inhaler Taifun, and a commercially available 50 microg dose(-1) dry powder inhaler Turbuhaler, and a conventional 100 microg dose(-1) pressurized metered-dose inhaler with a spacer (pMDI+S). Twenty-one patients, aged 21-70 years, with stable asthma and with demonstrated reversibility upon inhalation of salbutamol were included in the study. On three separate study days, the patients received a total dose of 400 microg of salbutamol from the dry powder inhalers and a dose of 800 microg from the pMDI+S in a cumulative fashion: 1,1, 2 and 4 doses at 30 min intervals. The percent change in forced expiratory volume in 1 sec (FEV1), was used as the primary efficacy variable. Salbutamol inhaled via the Taifun produced greater bronchodilation than the other devices. The difference in percent change in FEV1 between the Taifun and the other devices was statistically significant at the two first dose levels, but diminished towards the higher doses when the plateau of the dose-response curve was reached. The estimated relative dose potency of the Taifun was approximately 1.9- and 2.8 fold compared to the Turbuhaler and the pMDI+S, respectively. The Taifun caused a slight, but clinically insignificant, decrease in serum potassium concentration. There were no significant changes in the other safety parameters (blood pressure, heart rate and electrocardiogram recordings) with any of the used devices. In conclusion, this study indicates that salbutamol inhaled via the Taifun is more potentthan salbutamol inhaled from the other devices tested. In practise, a smaller total dose of salbutamol from theTaifun is needed to produce a similar bronchodilatory response. All treatments were equally well tolerated. PMID- 11778792 TI - Asthma, chronic bronchitis and respiratory symptoms among adults in Estonia according to a postal questionnaire. AB - Epidemiological studies indicate a lower prevalence of asthma in Eastern than Western Europe. This study of the prevalence of asthma, chronic bronchitis, and respiratory symptoms was performed in three different regions of Estonia, a state incorporated in the Soviet Union until 1991. A postal questionnaire was sent to a random sample of 24,307 of the population aged 15-64 years. The response rate was 77.6%. The prevalence of physician-diagnosed asthma was 2.0% or considerably lower than in Northern and Western European countries. The prevalence of wheezing last 12 months, 21.7%, recurrent wheeze, 13.3%, and attacks of shortness of breath, 12.5%, were similar or even higher compared with prevalence rates found in the Nordic countries. The prevalence of physician-diagnosed chronic bronchitis was 10.7%, and was higher among women than in men, although the proportion of current smokers among men, 57%, was considerably greater than in women, 28%. A possible explanation to the high prevalence of respiratory symptoms also among non-smoking women may be exposure to environmental tobacco smoke in small, crowded Estonian homes. Diagnostic criteria based on the Soviet-time definitions is discussed as a possible explanation to the low prevalence of physician diagnosed asthma and high prevalence of chronic bronchitis in Estonia compared with other Northern European countries. PMID- 11778793 TI - Measurement of peak inhalation rates with an in-check meter to identify an elderly patient's ability to use a turbuhaler. AB - Dry powder inhalers are designed with resistance to airflow so that a respirable cloud of particles is generated during inhalation. Some of these devices require a certain inhalation rate to produce a consistent dose of respirable particles. The aim of the study was to determine the inhalation rate of elderly patients with chronic obstructive pulmonary disease (COPD) when they inhale through a Turbuhaler and assess the potential of the In-Check Meter to identify inhalation rates. Their peak inhalation rate using a normal inhalation, pre- and post counselling, was measured using a Turbuhaler Trainer and an In-Check Meter. Spirometry was also measured. Seventy-four COPD patients with a mean (SD) age of 79.7 (8.4) years and forced expiratory volume in 1 sec (FEV1) 41.9 (12.8)% predicted. Pre-counselling 14 obtained a rate of <30 l min(-1) with the Turbuhaler Trainer, 31 from 30 to 40 min(-1), 23 between 40-60 l min(-1) and 6 > 60 l min(-1). The median (range) peak inhalation rates with the In-Check Meter were 50 (50-70), 70 (50-130), 100 (60-200) and 225 (200-250) l min(-1). Post counselling 7, 16,41 and 10 achieved the respective peak inhalation rates using the Turbuhaler Trainer Similarly the In-Check inhalation rates were 50 (50-60), 70 (50-130), 90 (60-200) and 250 (200-270) l min(-1). The results highlight the potential of the In-Check Meter to identify patients' inhalation rates through dry powder inhalers. PMID- 11778794 TI - Eosinophils in induced sputum from asymptomatic smokers with normal lung function. AB - Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD). However, only 10-15% of smokers develop the disease and early changes within the airways are poorly defined. We aimed to compare cell profiles in induced sputum (IS) from asymptomatic smokers to that from healthy subjects, and to ascertain whether or not inflammatory cells in IS are related to lung function and smoking habit. We recruited 34 heavy, non-allergic asymptomatic smokers with normal lung function and 15 healthy volunteers, who performed lung function tests and IS by hypertonic saline (3%) solution. In smokers, significantcorrelation between pack-years and FEF25-75 (rs = -0.43, P < 0.02) was found. In IS, smokers had higher counts of macrophages (P < 0.01) and eosinophils (P < 0.02), when compared to those of healthy subjects. Additionally, eosinophils were found in IS of 14 out of 34 smokers, with eosinophils had a higher pack years (31 +/- 25 vs. 13 +/- 10, P = 0.02) and lower FEF 25-75% value (78% +/- 34 vs. 100% +/- 23. P < 0.04). when compared to smokers without eosinophils. Additionally, on the basis of regression equations by stepwise multiple regression analysis, eosinophils were predicted by pack-years (r2 = 0.41). Our results showed that asymptomatic smokers have evidence of inflammatory cells in IS samples. In addition, we found thatthe degree of eosinophilic inflammation is related to early changes of lung function and can be predicted by smoking habit. PMID- 11778795 TI - Sexuality in chronic respiratory failure: coincidences and divergences between patient and primary caregiver. AB - Sexual functioning can be affected by chronic illness in a variety of ways. These problems affect the patients relationship and the degree of satisfaction with his partner. We conducted a study in order to evaluate the perception of sexual difficulties and changes in communication with patients and their wives. Male chronic obstructive pulmonary disease patients with (COPD) and chronic respiratory failure on long-term oxygen therapy were studied. The evaluation method used has consisted of the individualized administration of a semi structured interview created for this purpose. This interview was conducted with the patients and their wives. One part of the interview was dedicated to evaluating possible sexual problems and how these problems affect the relationship between the couples. In addition, patients as well as their partners were asked the degree of satisfaction with their partners and the degree of satisfaction with their lives. Forty-nine patients and their spouses have been included in the study. Thirty-three patients (67.3%) showed some type of sexual problem (lack of desire and/or impotence). Sixteen wives (33%) answered affirmatively to the question about whether changes at a communicative level as a consequence of the patients illness had occurred. In relation to the appearance of sexual changes, 46 (94%) of the wives answered affirmatively. The wives were significantly less satisfied with the relationship than the patients, which was related to communication problems. The group of patients were more satisfied with their partners than with their life, whereas no difference has been observed in the wives with both variables. An important percentage of patients with chronic insufficiency who have sexual difficulties exits. A factor which influences the perception of such problems in a very important way is the degree of affection in the relationship between the couples. PMID- 11778796 TI - Non-continuous home oxygen therapy: utilization, symptomatic effect and prognosis, data from a national register on home oxygen therapy. AB - About half of all patients on home oxygen therapy receive non-continuous oxygen therapy (less than 15 h daily) (NCOT). The goal of NCOT is to improve well-being during daily activities and to improve sleep quality. The aim of this study was to evaluate the effect of NCOT on pulmonary symptoms and sleep quality, and to determine whether patients with a subjective beneficial effect differed from those without effect in terms of patients' characteristics, utilization of oxygen, hospitalization and survival. Furthermore, the relationship between the reported beneficial effect of NCOT on dyspnoea and physical activity during domestic activities was examined. During the period November 1994 to July 1995, 254 Danish patients were prescribed oxygen less than 12 h daily or 'on demand'. Of these patients, 142 (55.9%) answered a questionnaire on hours spent with oxygen and symptomatic effect of oxygen treatment. While on oxygen, 76.3% of the patients reported improved dyspnoea score (0-10) more than 0.5 points, 78.3% had improved quality of life, 59.5% improved sleep, 48.5% increased physical activity, 49.3% felt less tired and 40.0% reported improved thinking. Fifty-seven (43.2%) patients reported both improved dyspnoea and physical activity whereas seven (5.3%) patients reported that oxygen had no effect on dyspnoea but a beneficial effect on physical activity Only 11 (7.7%) patients reported no subjective improvement on oxygen. The subjective effect of NCOT was not significantly associated to hours spent with oxygen. the underlying disease, gender, hospitalization or survival. During daily activity and regardless of daily number of hours spent with oxygen, NCOT improved well-being in nearly all patients. The most pronounced improvement was reported on dyspnoea, sleep and quality of life. Very few patients sensed improved physical activity without relief in breathlessness. PMID- 11778797 TI - Six-minute walking test in cystic fibrosis adults with mild to moderate lung disease: comparison to healthy subjects. AB - The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities. PMID- 11778798 TI - Cost analysis of the use of inhaled corticosteroids in the treatment of asthma: a 1-year follow-up. AB - A retrospective cohort using pharmacy and medical claims was analysed to determine whether the differences in efficacy of various inhaled corticosteroids demonstrated in clinical trials lead to differences in costs of care observed in clinical practice. Subjects that had an ICD-9 (493.XX) code for asthma and a new pharmacy claim for inhaled fluticasone propionate 44 mcg (FP), beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), budesonide (BUD) or flunisolide (FLU) were identified and followed for 12 months. Annual asthma care charges (pharmacy and medical) over the 12-month observation period were significantly (P < 0.03) higher in patients treated with BDPTAA, BUD and FLU compared to FP, 24%, 27%, 34% and 45% respectively In addition, patients treated with BDPTAA, and FLU were associated with significantly (P < 0.005) higher total healthcare (asthma + non-asthma) charges compared to patients on FP, 53%, 46% and 39% respectively Asthma care and total healthcare charges remained lower for FP after including FP110 mcg and excluding patients who were extreme cost outliers (+/- 2 SD from the mean) in a univariate sensitivity analysis. This analysis supports recent randomized control trials that FP offers a superior efficacy profile at lower asthma care as well as total healthcare charges compared to other inhaled corticosteroids. PMID- 11778799 TI - Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability. AB - The forced expiratory volume in 1 sec (FEV1) is the most established outcome measure in chronic obstructive pulmonary disease (COPD). However, changes in FEV1 in response to treatment are small in relation to the repeatability of the measurement and there is increasing interest in other measures including markers of lower airway inflammation in induced sputum, assessment of symptoms and health status using visual analogue scores, and questionnaires. Little is known about the repeatability of these measures or the safety of sputum induction in COPD. We have assessed the safety of sputum induction in 61 subjects with moderate and severe COPD who participated in a placebo-controlled cross-over study The within subject repeatability of sputum markers of airway inflammation, health status using the chronic respiratory disease questionnaire (CRQ) and symptom visual analogue scores (VAS) were estimated from the data obtained from before and after 2 weeks of treatment with placebo. Sputum induction was performed on 122 occasions and was successful resulting in a cytospin adequate to assess a differential cell count in 95% of inductions. The group mean (SEM) FEV1 was 1.09 (0.05)[41.6 (2.9)% predicted] and the mean (SEM) fall in FEV1 after sputum induction was 120 ml (6) and % fall 10.9% (0.55%). Seven inductions were stopped due to a fall in FEV1 >20% and at a further 13 visits the full sputum induction protocol was not completed due to development of symptoms. The reproducibility of measurements, calculated by the intra-class correlation coefficient, was relatively high for all indices measured (0.4-0.95) with the exception ofthe proportion of lymphocytes (0.15) and epithelial cells (0.3). The ICC for symptom scores and the CRQ domains ranged between 0.87 and 0.96. In conclusion, sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD. VAS symptom scores and the CRQ are reproducible outcome measures in COPD. PMID- 11778800 TI - Understanding keratoconus. PMID- 11778801 TI - Is the corneal degradation in keratoconus caused by matrix-metalloproteinases? AB - The thinning of the cornea that occurs in keratoconus has been well described; however, the mechanism of tissue degradation remains unknown. Elevated proteinase activity is one possibility and approximately 20 publications over the last 20 years have addressed this hypothesis. Early studies reported increased collagenase and gelatinase activities in the medium of keratoconus corneal cultures. After the characterization of the matrix metalloproteinase (MMP) enzymes, studies focused on the expression of specific MMPs, in particular the gelatinases, MMP-2 and MMP-9. Matrix metalloproteinase-2 was found to be the major MMP of the cornea and was constitutively produced in normal tissue, whereas MMP-9 expression was induced by various stimuli, including phorbol esters and even tissue culturing. These studies suggested that there were no differences in the amounts or states of activation of MMP between normal and keratoconus corneas, although the amounts of some proteinase inhibitors, including tissue inhibitors of metalloproteinases, alpha-1-proteinase inhibitor and alpha-2 macroglobulin, were decreased in keratoconus. Most recently, the lysosomal proteinases, cathepsin B and cathepsin G were reported to be elevated in keratoconus corneas, and it is possible that it was cathepsin activity, not MMP activity, that was measured in some early studies. Nevertheless, there are now about 20 human MMPs identified and it is possible that some of these, other than the well known collagenase (MMP-1) and gelatinases (MMP-2 and MMP-9), could be implicated in the pathology of keratoconus. Studies have begun to address more recently described MMPs and it has been reported that the membrane-bound MT1-MMP (MMP-14), which activates latent MMP-2, was found to have increased expression in keratoconus corneas, whereas the stromelysins, MMP-3 and MMP-10, were not. PMID- 11778802 TI - The genetics of keratoconus. AB - Keratoconus is a relatively common, bilateral, non-inflammatory corneal ectasia. The aetiology of this condition is probably multifactorial, or it represents the final common pathway for a variety of different pathological processes. Although a familial history is present only in a minority of cases, one of the major aetiological factors is certainly genetic. This is evidenced by: the condition's familial inheritance; its discordance between monozygotic and dizygotic twins; and its association with other known genetic disorders such as Down's and Marfan's syndromes. In the keratoconic cornea, a possible genetic predisposition to increased sensitivity to apoptotic mediators by keratocytes has also been hypothesized. Differences in prevalence between ethnic groups have been identified. Recent advances in computerized topographic diagnostic techniques for keratoconus, including forme fruste keratoconus, enables higher accuracy in delineating abnormal from normal, and helps define study populations for genetic linkage studies. However, genetic heterogeneity and the phenotypic diversity of keratoconus means that genetic analysis continues to be a complex process. None the less, it is foreseeable that over the next decade, improved diagnostic techniques, in combination with molecular genetics, may reveal conclusive data on the precise nature of the genetic inheritance of keratoconus in specific populations. This review considers the evidence that suggests keratoconus is primarily an inherited condition, and examines research strategies aimed at unveiling the genetic predisposition, and the enigma of environmental influences on its phenotypic expression. PMID- 11778803 TI - Frequency of sustained glaucomatous-type visual field loss and associated optic nerve cupping in Beaver Dam, Wisconsin. AB - PURPOSE: To determine the prevalence of persisting glaucomatous-type visual field loss in a Midwestern American adult population, in association with four grades of disc cupping. METHODS: On two separate occasions (1988-1990 and 1993-1995) 2955 predominantly Caucasian adults aged 43-84 provided medical history, underwent applanation tonometry, slit-lamp examination, quantitative suprathreshold perimetry and stereoscopic disc analysis as part of the National Institutes of Health-sponsored Beaver Dam Eye Study. Those demonstrating evidence of glaucomatous-type visual field loss at both visits were the subject of the present analysis. Among these individuals, associations were determined for four categories of optic disc cupping (vertical cup/disc < 0.5, > 0.5, > 0.6, > 0.8), intraocular pressure, blood pressure, cardiovascular pathology and prior glaucoma diagnosis. RESULTS: Of the 2955 subjects assessed, 120 (4%; 57 women, 63 men) demonstrated glaucomatous-type visual field defects at each visit. Fifty-five of these 120 (2% of the tested population) also exhibited some degree of disc cupping in a related eye at both visits. Among these 2%, positive associations relating the extent of field loss, cupping and intraocular pressure were confirmed, but the majority in each cupping category had normal eye pressures. Only seven of the 120 were aware of the presence or suspicion of eye disease prior to the screening. CONCLUSIONS: A majority of those found to have visual field loss and optic nerve cupping persisting together in the same eye after 3-5 years had normal pressures in each eye at both visits. Despite good access to medical care, very few who demonstrated persisting cupping and field loss (even among those with elevated eye pressure) were aware of their ocular condition through prior contact with an eye care professional. PMID- 11778804 TI - Comparison of three tests using the frequency doubling illusion to diagnose glaucoma. AB - PURPOSE: The introduction of the FDT perimeter prompted the comparison of three tests employing frequency doubling (FD) stimuli. These measures compared different visual field locations and contrast ranges. Frequency of seeing curves were examined for the method most similar to FDT. METHODS: For 146 eyes the following were obtained: (i) contrast matches to two suprathreshold FD stimuli (normal subjects, ocular hypertensve suspects, primary open angle glaucoma subjects); (ii) two alternative forced choice (2AFC) thresholds for horizontally versus vertically orientated FD gratings: and (iii) contrast thresholds determined by method of adjustment (MOA) for five different stimulus types. RESULTS: A model based on the worst of the MOA hemifield thresholds performed best. The suprathreshold contrast matching tests performed worst. Frequency of seeing curves were fitted for the 146 eyes of the 2AFC tests. Although the MOA thresholds were higher than the 2AFC thresholds (for normals mean +/- SE, 8.47 +/ 0.43 dL, P < 0.0000), the best diagnostic concordance was at lower limens (75% or 80% correct) of the fitted frequency of seeing curves. CONCLUSIONS: There was good diagnostic concordance between the MOA and 2AFC methods although the thresholds were 1.8-fold different on a log-scale. This suggests that the same neural mechanism mediates both thresholds for rapidly flickering, spatially coarse, patterns. PMID- 11778805 TI - The latanoprost monotherapy survey in New Zealand, 2000. AB - BACKGROUND: A State subsidy for latanoprost has been recently introduced. It is subject to several conditions including that it should only be used as monotherapy. METHOD: A prospective survey of all New Zealand ophthalmologists was undertaken to determine the outcome of the widespread trial of latanoprost monotherapy. The return rate was 82%. RESULTS: Of 2900 patients on latanoprost nation-wide, 14.7% were monotherapy failures. Of these, 93% were due to inadequate intraocular pressure control but this subgroup had adequate control on two or more medications in 88%. Ophthalmologists had 635 patients that were not trialed as monotherapy, of which 565 (89%) were due to a perceived risk. CONCLUSIONS: In those patients treated with latanoprost, 85% were adequately controlled as monotherapy. PMID- 11778806 TI - Pterygium in Australia: a cost of illness study. AB - PURPOSE: The aim of this report was to describe the number of Australians affected by pterygium in recent years, treatment options, number of treatment encounters and costs of treatment. METHOD: A review of published literature was conducted to identify the prevalence of pterygium in Australian populations. Costs of primary care were based on national general practitioner (GP) survey data. Costs of surgical intervention were based on Health Insurance Commission claims data and Australian Institute of Health and Welfare National Hospital Morbidity Data. RESULTS: Pterygium occurs in 1.1% of Australians. It is more prevalent in populations with higher exposure to ultraviolet radiation, and older men (occurring in 12% of males over 60 years). The estimated annual number of GP contacts was 58,900. Forty per cent of primary care contacts for pterygium were referred to an ophthalmologist and topical medication was prescribed by GPs in 32% of contacts. The estimated annual cost of GP visits, specialist visits and topical medication was AUD$3.2 m. There were 6997 claims for pterygium removal in 1999/2000 with 3192 conjunctival autografts. Rates of pterygium removal were highest in Queensland with 56 per 100,000 population. The annual costs of surgical intervention were estimated at AUD$4.8 m. CONCLUSIONS: The direct medical costs of pterygium in Australia are AUD$8.3 m annually. This is likely to be an underestimate of total cost because indirect costs such as loss of work time could not be measured. More data are needed on the long-term benefits of pterygium intervention. PMID- 11778807 TI - The waiting game: natural history of a cataract waiting list in New Zealand. AB - AIMS: To identify the demographic and visual function of patients on the reserve waiting list for cataract surgery at a large public hospital within New Zealand and to determine the ultimate outcome of those on a priority-based, rationed, health-care waiting list. METHODS: Patients from a defined geographical population, placed on a reserve waiting list for possible cataract surgery, during the period January 1997 to March 2000, were invited to attend for further clinical assessment and asked to complete a visual assessment questionnaire. RESULTS: Of 193 patients in the pilot study group who had been on the reserve waiting list for a mean of 18.2 +/- 11.6 months (range 0.1-62.7 months), only 94 (49%) were deemed suitable for, and subsequently underwent, surgery in the public sector. Forty-nine (25%) had undergone surgery earlier, the majority of these (84%) in the private sector. A further 23 (12%) patients were deceased, four (2%) declined surgery and in six (3%) cataract surgery was no longer indicated. The remaining 11 (6%) patients could not be traced. Patients still awaiting surgery had a mean age of 77.2 years (range 48-95 years). Fifty-four were women. Vision had deteriorated by a mean of 0.05 LogMAR units, from Snellen equivalent 6/30 at listing to 6/36, over this time. CONCLUSIONS: Current methods of prioritization for cataract surgery are imperfect, as are the resources for performing adequate levels of cataract surgery. Analysis of a residual waiting list for cataract surgery highlights that the majority (51%) do not ultimately progress to cataract surgery in the public sector for a variety of reasons. During a mean waiting time of 1.5 years vision further deteriorates in this predominantly older population. PMID- 11778808 TI - The Auckland Cataract Study: demographic, corneal topographic and ocular biometric parameters. AB - PURPOSE: To determine patient demographics and the ocular biometric parameters in patients presenting for cataract surgery within the public hospital system, in a defined New Zealand population. METHOD: Prospective study of 502 eyes of 488 consecutive patients undergoing cataract surgery. A clinical assessment, including refraction, keratometry (K), A-scan ultrasound and Orbscan II computerized topography was performed on each eye. RESULTS: The mean age of the group was 74.9 +/- 9.8 years (mean +/- SD) with a female predominance (62%). Ethnic origin included 72% European, 8% Maori, 10% Pacific Islander, 4% Asian, 3% Indian and 3% other ethnic origins. The mean Log MAR visual acuity of eyes prior to cataract surgery was 0.88 +/- 0.57 (approximately 6/48(-1)). Corneal topographic (keratometric) maps were classified into five groups: 34% round, 10% oval, 31% symmetrical bow tie, 12% asymmetrical bow tie and 13% irregular. The mean steepest K measurement was 44.1 +/- 1.7 D, the median keratometric astigmatism 0.89 D (range 0.0-6.5 D) and the steepest corneal meridian was horizontal in 50% and vertical in 43%. Seven per cent of corneas were spherical. Refraction revealed a mean sphere of 0.0 +/- 3.1 D and a mean cylinder of -1.2 (range 0.0-7.5 D). Refractive astigmatism was with-the-rule in 15%, against-the rule in 50% and oblique in 15%, with 20% spherical. Axial length was a mean of 23.14 +/- 1.03 mm. CONCLUSION: Patients presenting for cataract surgery in this study were predominantly elderly, female, of European Caucasian ethnicity and exhibited relatively poor corrected visual acuity in the affected eye. Interestingly, 41% of eyes demonstrated bow-tie topographic patterns, largely exhibiting with-the-rule astigmatism. However, assessment by keratometry or refraction highlighted against-the-rule more frequently; this may have implications for combined cataract and astigmatic surgery. The mean axial length was slightly shorter than expected for a group of predominantly European ethnic origin, although the mean refractive error was emmetropic. PMID- 11778809 TI - Ocular adnexal lymphoproliferative disease: a series of 73 cases. AB - BACKGROUND: This study involved 73 patients with lymphoproliferative lesions of the ocular adnexa. The lesions were categorized using the Revised European American Lymphoma classification of lymphoid tissues and analysed to determine the frequency and prognostic impact of tumour type, location, stage and patient's age and sex. METHODS: The clinical, histopathological, immunohistochemical and phenotypic analysis by flow cytometry and follow-up data were studied. RESULTS: The ocular adnexal lymphoproliferative lesions included 70 lymphomas and six reactive lymphoid hyperplasia. Seventy-nine per cent had stage IE disease, 4% stage II, 1.5% stage III and 15.5% stage IV. Five patients (7%) had a past history of systemic lymphoma. Major histological types were extranodal marginal zone lymphoma (MZL) in 44 (63%), follicular (FL) in 12 (17%), diffuse large B cell (DLBCL) in eight (11%), mantle cell (MCL) in two (3%), B-cell chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma in two (3%), peripheral T cell lymphoma (PTCL) one (1.5%) and natural killer cell lymphoma (NKCL) in one (1.5%). Longest survival was seen in those with low-grade lymphomas (MZL and FL) and worst in PTCL and NKCL. Lymphoma-related mortality was 2% for MZL, 33% for FL, 38% for DLBCL, and 100% for MCL, PTCL and NKCL. Systemic lymphoma was present prior to, at presentation or at subsequent follow up in 26/68 (39%) of all lymphoma patients, 17% for MZL, 38% for DLBCL, 83% for FL, and 100% for MCL, CLL, PTCL and NKCL. CONCLUSION: The majority of ocular adnexal lymphomas were low grade B-cell lymphomas (MZL). Multivariate analysis showed that the only significant independent predictors of all causes of mortality were the histological type of lymphoma and the stage of disease at presentation. PMID- 11778810 TI - An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis. AB - PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A (BOTOX, Allergan) when used to produce a protective ptosis in patients where a surgical tarsorrhaphy would otherwise be required. METHODS: A total of 21 patients entered into the study. Doses of 2.5 and 5.0 units of BOTOX were injected into the levator palpebrae superioris muscle through the eyelid. The patients were followed daily where practical until a ptosis developed and then monitored 1-2 weekly until the ptosis was resolved. Injections were repeated, if necessary until the underlying condition had healed. RESULTS: Ptosis took an average +/- SE of 4.0 +/- 0.5 days to develop (range 2-8 days). Duration of ptosis was an average +/- SE of 46.0 +/- 12.1 days (range 1-206 days). The effective dosage was 5 units of BOTOX in 0.1 mL. In 16 patients, the ptosis produced by BOTOX was sufficient to allow the underlying disease to heal and a surgical tarsorrhaphy was avoided. One patient required a surgical tarsorrhaphy and three patients required other surgical intervention to correct the underlying condition. One patient was lost to follow up. Diplopia was seen in five patients but resolved in all cases. CONCLUSIONS: BOTOX was a suitable alternative to a surgical tarsorrhaphy. PMID- 11778811 TI - Endophthalmitis in the western Sydney region: a case-control study. AB - BACKGROUND: A retrospective case-control study was conducted to investigate risk factors for endophthalmitis following routine intraocular surgery. METHODS: A review was performed of consecutive cases of endophthalmitis from three teaching hospitals in the western Sydney region and matched controls from the same institutions between 1996 and 1998. RESULTS: There were 31 cases and 66 controls. Eighty procedures were phacoemulsification, 15 conventional extracapsular cataract extraction, and two were penetrating keratoplasties. Of the 80 patients who had phacoemulsification surgery, 50 had a clear corneal incision, and 26 had a scleral incision (four were unknown). Logistic regression showed an increased risk of endophthalmitis with surgical complications (P = 0.002) and clear cornea temporal incisions (P = 0.007). Risk of endophthalmitis was reduced with use of subconjunctival injections (P = 0.008). The yield for the Gram stain was 47% and for culture was 67%. Anterior chamber tap in addition to vitreous biopsy alone did not increase the yield for microorganism (P = 0.78). Mean visual acuity on presentation was hand movement with 13 patients (50%) showing visual improvement following intravitreal injections of antibiotics (P = 0.003). Visual prognosis did not correlate with presenting visual acuity but appeared to be better in those who grew Staphylococcus epidermidis or were culture negative. CONCLUSIONS: Although this study is unable to draw definite conclusions regarding risk of endophthalmitis in clear corneal temporal cataract surgery, sufficient data suggest the importance of incision type and location. Surgical complication is an important risk factor for endophthalmitis. Use of subconjunctival antibiotic injections at the conclusion of the procedure is recommended. PMID- 11778812 TI - Uveitis in Herpes zoster ophthalmicus. AB - BACKGROUND: Herpes zoster ophthalmicus (HZO) is a common condition occurring mostly in healthy people. Approximately 50% of HZO patients develop ocular complications, with iridocyclitis occurring in about 43%. This study aimed to identify the clinical features of uveitis secondary to HZO. METHOD: A retrospective case study was performed of consecutive patients with HZO and secondary uveitis seen in the past 10 years at the Royal Victorian Eye and Ear hospital as well as those seen in the private clinics of two ocular immunology consultants. The information collected included the time relationship between onset of rash and uveitis, duration and treatment of the uveitis, and rate and nature of ocular complications. RESULTS: Thirty-four patients fulfilled the enrolment criteria. The age range was from 24 to 83 years with an average age of 62.5 years. Of these, 28 patients (82%) were immunocompetent and six patients (18%) had underlying immunosuppression from various causes. Twenty-three patients had a uniphasic episode of uveitis and 11 patients (32%) had a chronic relapsing course of uveitis. The duration of the uveitis was variable, ranging from 1 week to 3 years, with 68% of episodes resolving within 2 months. Nineteen patients (56%) developed secondary glaucoma. Five of these patients (26%) required trabeculectomies to control their intraocular pressures. Three patients (9%) had bilateral ocular involvement and five patients (15%) had a reduction in final Snellen visual acuity of more than two lines. CONCLUSION: In this study, most patients were immunocompetent individuals. The course of the uveitis was generally uniphasic in nature and of a relatively short duration. There was a high incidence of secondary glaucoma with 15% of all patients requiring surgical intervention. The visual loss in the five patients was not directly related to the uveitis and secondary glaucoma but to other complications associated with HZO. PMID- 11778813 TI - Carotid dissection: a common cause of Horner's syndrome. AB - PURPOSE: To highlight that internal carotid artery dissection is a common cause of Horner's syndrome and that it is important to diagnose dissection as anticoagulation can prevent carotid thrombosis and embolism. METHODS: Five case reports are presented of patients with Horner's syndrome secondary to carotid dissection. One patient had carotid dissection secondary to trauma, two had spontaneous dissections and two had dissections in the settings of other illness. A literature search was performed on carotid dissection as a cause of Horner's syndrome and its diagnosis and management. RESULTS: The case reports and literature highlight that dissection is under-recognized as a cause of Horner's syndrome and can be missed. The investigation of choice is a magnetic resonance imaging and angiography scan of the head and neck. The treatment advocated is anticoagulation for 3-6 months. CONCLUSION: Carotid dissection should be suspected in patients with Horner's syndrome, particularly if head or neck pain is present. PMID- 11778814 TI - Undergraduate ophthalmology education survey of New Zealand ophthalmologists, general practitioners and optometrists. AB - AIM: To determine what New Zealand ophthalmologists, general practitioners and optometrists consider important ophthalmic topic areas requiring emphasis in the medical undergraduate curriculum. METHOD: A total of 793 questionnaires related to the content and teaching of undergraduate ophthalmology were sent to ophthalmologists, general practitioners and optometrists. Results were analysed separately for the three respondent groups and as a whole. RESULTS: Four hundred and fourteen questionnaires were returned (52% return rate). Overall responses of the three participant groups were similar and agreed favourably with the current curriculum. The ability to measure visual acuity (97%) and pupillary reflexes (93%), perform ophthalmoscopy (92%), and assess visual fields (68%) were regarded as 'important or essential' by the majority of respondents. Only 53% of respondents consider the ability to diagnose chronic open angle glaucoma as important. The respondents stressed the importance of the diagnosis of predominantly anterior segment disease contrasting with the traditional bias towards the teaching of ophthalmoscopy and posterior segment disease. The majority of respondents stressed the importance of graduating medical students being able to treat bacterial and allergic conjunctivitis, styes, blepharitis, corneal abrasion, and corneal and conjunctival foreign bodies, areas present but not normally emphasized in current curricula. CONCLUSION: The findings of this study provided additional data to facilitate curriculum design and illustrated the value of an integrated problem-based learning approach in ophthalmology undergraduate teaching. PMID- 11778815 TI - Proliferation of lens epithelial cells on the Acrysof intraocular lens: clinical and histological features of a case. AB - Postoperative deposits on the surface of intraocular lenses (IOLs) have been demonstrated in vivo for many IOL material types. The Acrysof acrylic lens develops a granular material extending from the capsulorhexis margin onto the IOL's anterior surface during the first 4 weeks after surgery in a significant proportion of cases. Complete resolution of this membrane occurs by 3 months in almost all cases. The case is presented of an 81-year-old woman who had a persisting membrane coverng the IOL surface at 6 months. This membrane was removed surgically and pathology showed the constituent cells to be of lens epithelial cell origin. PMID- 11778817 TI - Failure of antiretroviral therapy to control Varicella zoster retinitis. AB - The term necrotizing herpetic retinopathies encompasses a spectrum of diseases which includes cytomegalovirus (CMV) retinitis, acute retinal necrosis (ARN) and Varicella zoster retinitis (VZR). Varicella zoster retinitis is a rapidly progressive, necrotizing condition most commonly reported in patients with AIDS. A case of vitreous biopsy-proven VZR is reported in a patient with AIDS that progressed despite immune recovery on highly active antiretroviral therapy (HAART) to a viral load < 50 copies/mL and a CD4 count of 230 cells/microL. This is in contrast to CMV retinitis in which maintenance therapy appears unnecessary once the CD4 count rises and the viral load falls on HAART. Patients with VZR and AIDS should therefore be monitored for reactivation of retinal disease despite HAART-induced remission. PMID- 11778816 TI - Multifocal chorioretinal atrophy associated with herpes zoster ophthalmicus. AB - A 73-year-old woman developed multiple depigmented lesions in the fundus 4-6 months after an episode of acute Herpes zoster ophthalmicus. Post-mortem examination of the globe 15 years after this acute episode confirmed multiple old chorioretinal scars probably due to vasculitis of the short posterior ciliary arteries and branches. Patchy old infarcts were also noted in the iris. PMID- 11778818 TI - Delayed diffuse lamellar keratitis after laser in situ keratomileusis. AB - Two cases are reported of delayed diffuse lamellar keratitis after uneventful laser in situ keratomileusis. The first patient presented with an epithelial defect 6 weeks after laser in situ keratomileusis. Three days later the defect was healed but diffuse lamellar keratitis was noted. This was treated with topical dexamethasone and ketorolac with complete resolution of the diffuse lamellar keratitis over 3 weeks. The second patient presented with an epithelial defect and gross diffuse lamellar keratitis 10 weeks after laser in situ keratomileusis. Treatment was with topical dexamethasone and ciprofloxacin with gradual resolution of the diffuse lamellar keratitis. Common to both patients was a background of rosacea, implanted debris with no initial reaction, and epithelial defects leading to diffuse lamellar keratitis. It is suggested that these two cases represent epithelial defect associated corneal infiltration, which resembles classical diffuse lamellar keratitis with the spread of inflammatory cells through a path of least resistance. PMID- 11778819 TI - Bowel carcinoma metastatic to the retina. AB - The case is presented of metastatic carcinoma to the retina in a 63-year-old woman with known disseminated large bowel carcinoma. The clinical appearance and angiographic features are discussed. PMID- 11778820 TI - Is it not in my records, doctor? PMID- 11778821 TI - Intracranial dysembryogenetic tumors: pathogenesis and their order of malignancy. AB - Dysembryogenetic tumors can be classified into three main categories: (1) tumors derived from embryonal cell rests in situ such as craniopharyngioma, Rathke's cleft cyst, chordoma, etc., (2) tumors derived from embryonal cells straying into the tissue ("verirrte Keime") such as so-called germ cell tumors, epidermoid, dermoid, lipoma, hamartoma, etc., and (3) included twin (fetus-in-fetu) tumors. The pathogenesis of the second one may be that the embryonic cells of various stages of embryogenesis are misplaced in the bilaminar embryonic disc at the time of the primitive streak formation, becoming involved in the stream of lateral mesoderm and carried to the neural plate area to become incorrectly enfolded into the brain at the time of neural tube formation. The third category of tumor may be related to sequestration of cells of the blastocyst before differential blocking of the genome has occurred. The author propounds the following hypothesis: intracranial dysembryogenetic tumors composed of cells resembling the cells that appear in the earlier stages of embryogenesis are more malignant than those composed of cells resembling those appearing in the later stages of embryogenesis. PMID- 11778822 TI - Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology. AB - A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods. PMID- 11778823 TI - Intrathecal administration of nicardipine hydrochloride to prevent vasospasm in patients with subarachnoid hemorrhage. AB - OBJECT: To evaluate the prophylactic effect of repeated intrathecal administration of nicardipine associated with hypertensive hypervolemic hemodilution therapy (triple H) and sodium correction, we analyzed a consecutive series of 177 patients with subarachnoid hemorrhage. METHODS: All patients received aneurysmal clipping and placement of cisternal drainage within 48 hours of the onset. Intrathecal administration of 4 mg of nicardipine was performed every 12 h. Nicardipine concentrations in the cerebrospinal fluid (CSF) and blood before and after its administration were analyzed. Angiographic vasospasm (aVS), symptomatic VS (sVS), and clinical outcome 6 months after onset were also evaluated. RESULTS: Nicardipine concentration in CSF on day 9 was 231.44 +/- 51.51 ng/ml (mean +/- SD), and that of blood was 21.05 +/- 15.57 ng/ml. Twenty patients (11.3%) showed aVS, and ten of those (5.7%) showed sVS (six were transient and four were permanent). Those with good outcome (assessed as good recovery and moderately disabled) 6 months after onset were 89.2% of the total. The number of patients requiring a shunt operation was 33 of 177 (18.6%), and 11 patients presented intracranial infection. CONCLUSIONS: These results suggest that our strategy may well prevent VS. However, hydrocephalus and infection may be serious disadvantages that should be resolved. PMID- 11778824 TI - Influence of intraventricular hemorrhage on outcome after rupture of intracranial aneurysm. AB - This study was performed to analyze the effect of intraventricular hemorrhage (IVH) on 14-day mortality, outcome at 6 months, and the occurrence of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage. Clinical grade of subarachnoid hemorrhage and the distribution of extravasated blood were evaluated in 219 patients with ruptured aneurysms. Computed tomographic scans performed within 72 h of hemorrhage were analyzed to determine the severity of intraventricular and subarachnoid hemorrhage and the volume of intracerebral hematomas. Outcome at 6 months was assessed using the Glasgow Outcome Scale. Intraventricular hemorrhage extension occurred in 109 of the 219 patients studied. Fourteen-day mortality increased from 7.3% in patients without IVH to 14.1% in those with moderate IVH (IVH score 1-6) and to 41.7% in those with more severe IVH (IVH score > 6). The corresponding figures for unfavorable outcome at 6 months are 19.8%, 30.5%, and 66.7%, respectively. According to logistic regression analyses, the severity of IVH was an independent predictor of mortality and functional outcome. The clinical outcome after aneurysm rupture is at least in part determined by the severity of IVH. Knowledge of the effect of IVH may help guide physicians in the care of patients with aneurysmal bleeding. PMID- 11778825 TI - Clinical outcome differences for lipomyelomeningoceles, intraspinal lipomas, and lipomas of the filum terminale. AB - Failure to differentiate between the different types of lumbosacral lipomas may lead to inaccurate assumptions and inappropriate management of patients. The goal of this study was to determine whether there is a difference in clinical outcome between patients with lipomyelomeningocles, intraspinal lipomas, and lipomas of the filum terminale. One hundred and fourteen patients with spinal dysraphism were seen at Duke University Medical Center between 1995-1999. All patients who had undergone previous operative intervention for these lesions were excluded. Twenty-two patients with intradural lipomas were identified. Of these, 14 (64%) had lipomyelomeningoceles and 8 (36%) had intraspinal lipomas. Twenty-five patients had filum terminale lipomas. Operative management consisted of lumbosacral laminectomies with microsurgical resection of the lipoma and division of the fatty filum. Average age at presentation in symptomatic patients with lipomas of the filum terminale was 17.7 years, and 23 years in the symptomatic intraspinal lipoma group. Patients with lipomyelomeningoceles ranged in age from 1 day to 18 years, with the majority being younger than 2 years. After an average follow-up of 8 months all patients showed improvement in motor strength following operative intervention. Greater improvements in sensory, bladder, and pain scores were associated with filum terminale lipomas. The least improvements in these categories were seen in the lipomyelomeningocele group. Motor strength is the most likely deficit to improve following operative intervention. Lipomyelomeningoceles, intraspinal lipomas, and filum termniale lipomas have different clinical outcomes following operative intervention. PMID- 11778826 TI - Radiographic evaluation of posterolateral lumbar fusion for degenerative spondylolisthesis: long-term follow-up of more than 10 years vs. midterm follow up of 2-5 years. AB - Although posterolateral fusion of the lumbar spine without instrumentation has been widely performed for spinal instability caused by degenerative spondylolisthesis in the lumbar spine, few long-term follow-up studies have been reported. We studied ten patients who underwent posterolateral fusion for degenerative spondylolisthesis in the lumbar spine without instrumentation in our hospital, five of whom were followed up for more than 10 years and the other five for 2-5 years. We used radiography to examine their fusion status, instability and degenerative changes at the fusion level, change in the slip, change in lumbar lordosis, and instability and degenerative changes one level above and one level below the fusion. In most of the ten patients, radiographic evaluation demonstrated solid fusion, minimal degenerative changes, and preservation of lumbar lordosis and spinal mobility. Posterolateral lumbar fusion for degenerative spondylolisthesis in the lumbar spine seems promising for obtaining not only good radiographic features but also good clinical results lasting over more than 10 years. PMID- 11778827 TI - Intracranial hydatidosis in Turkey: its clinical presentation, diagnostic studies, surgical management, and outcome. A review of 276 cases. AB - Hydatid disease is still a major health problem in the infested areas of the world, especially in rural areas. Two hundred seventy-six Turkish cases with intracranial hydatidosis have been published since 1960. Based on the records of these cases, the clinical data, neuroradiological findings, treatment, and outcome of intracranial hydatidosis are reviewed. Demographically seen, there was a substantial prevalence of male patients--167 cases (61%). Most of the patients with intracranial hydatidosis were from rural areas and the cysts were generally located in the cerebral hemispheres. In 100 patients, two or three lobes were affected and the cysts were multiple in 53. This infestation was also reported in rare locations such as the ventricular system, extradural space, posterior fossa, pons, sella turcica, parasellar area, and cavernous sinus. Only 49 patients (18%) had other organ infestation. The majority were operated on immediately after diagnosis was established. Operative mortality was 9% and postoperative complications developed in 26 patients. In my reference studies, only 16 cases of recurrence have been seen. This study confirms that hydatid disease is a difficult health problem in Turkey and demonstrates that surgery plus chemotherapy has considerably improved the prognosis, but local disinfectant application is not useful to devitalize the cystic contents. The dimensions, localization and numbers of the cysts are important determinants of the outcome. PMID- 11778828 TI - Avoidance of vascular compression in decompressive surgery for brain edema caused by trauma and tumor ablation. AB - BACKGROUND: In case of severe brain swelling especially caused by trauma or other operative manipulation (tumor ablation), decompressive craniectomy with durotomy has not resulted in significant chances of recovery. Decompressive craniectomy has been defined only as an option within guidelines. METHOD: A new operative technique was developed to improve the efficacy of decompressive surgery. With an increase in intracranial pressure (ICP) threatening with brainstem herniation, wide bilateral craniectomy was carried out, followed by dura opening and subsequent formation of a vascular tunnel in a simple way--using hemostatic sponge cushions--around the main cortical veins at the entering points of the herniated area. The maintenance of vessel patency prevents the herniated brain segment from venous congestion, i.e., from further swelling and necrosis. RESULTS: Twenty operations with traumatic brain edema were performed using this vascular tunnel method. All patients were exposed to surgery in the state of coma. One operation was performed after tumor removal. The results were promising in comparison with the well-known surgical or conservative treatment. DISCUSSION: Applying very strict selection criteria (Glasgow coma scale < 6, signs of severe edema on CT, or intracranial pressure permanently > or = 30 mmHg) in this small series of patients with severe brain injury, good results were achieved using the new operative technique. In case of postoperative edema after tumor ablation, it also showed promising results. PMID- 11778829 TI - Cerebellar haemorrhage after supratentorial aneurysm surgery with lumbar drainage. AB - Haemorrhage within the posterior fossa (PF) after supratentorial surgery is a very rare and exceedingly dangerous complication. Only 28 cases were found in the literature. Up to now, no pathogenetic factor has decisively proven to be the cause of this phenomenon. We present clinical details of a patient operated on for aneurysm of the anterior communicating artery. Lumbar drainage was used during surgery, with the loss of a large amount of cerebrospinal fluid (200 ml). Other causes in our case which may have led to cerebellar shift or a critical increase in transmural venous pressure with subsequent vascular disruption and haemorrhage were extreme head rotation during lengthy surgery and blood pressure peaks in the early postoperative period. Repeated computed tomography (CT) allowed immediate diagnosis of this complication and control of its conservative management. After postponed ventriculoperitoneal shunt, the patient recovered completely. PMID- 11778830 TI - Adaptations for rapid and forceful contraction in wing muscles of the male golden collared manakin: sex and species comparisons. AB - The courtship display of the male golden-collared manakin (Manacus vitellinus) of Panamanian rainforests is noteworthy for several types of whip-crack-like sounds created by a rapid overhead flip of the wings. We have hypothesized that this courtship behavior. which is not performed by females, is associated with steroid sensitive and sexually dimorphic neuromuscular systems. Presumably, muscles creating the motion of the wingsnap in males are specialized for greater force generation and speed of contraction. We tested this hypothesis by examining mass, fiber diameter, metabolic enzyme activity, and myosin isoform expression in several muscles of male and female manakins and in both sexes of a non wingsnapping bird, the zebra finch (Taenopygia guttata). We have identified three wing muscles, the scapulohumeralis caudalis, the supracoracoideus, and the pectoralis major, that differ in one or more of these characteristics across sex and species, suggesting they are specialized for faster contraction and greater force production in male manakins. These muscles normally function to raise and lower the wings during flight. As this movement is the principal motion of the wingsnap, these adaptations presumably underlie the performance of the wingsnap display. PMID- 11778831 TI - Variations in cone photoreceptor abundance and the visual ecology of birds. AB - The relative abundance and topographical distribution of retinal cone photoreceptors was measured in 19 bird species to identify possible correlations between photoreceptor complement and visual ecology. In contrast to previous studies, all five types of cone photoreceptor were distinguished, using bright field and epifluorescent light microscopy, in four retinal quadrants. Land birds tended to show either posterior dorsal to anterior ventral or anterior dorsal to posterior ventral gradients in cone photoreceptor distribution, fundus coloration and oil droplet pigmentation across the retina. Marine birds tended to show dorsal to ventral gradients instead. Statistical analyses showed that the proportions of the different cone types varied significantly across the retinae of all species investigated. Cluster analysis was performed on the data to identify groups or clusters of species on the basis of their oil droplet complement. Using the absolute percentages of each oil droplet type in each quadrant for the analysis produced clusters that tended to reflect phylogenetic relatedness between species rather than similarities in their visual ecology. Repeating the analysis after subtracting the mean percentage of a given oil droplet type across the whole retina (the 'eye mean') from the percentage of that oil droplet type in each quadrant, i.e. to give a measure of the variation about the mean, resulted in clusters that reflected diet, feeding behaviour and habitat to a greater extent than phylogeny. PMID- 11778832 TI - Free-field unmasking response characteristics of frog auditory nerve fibers: comparison with the responses of midbrain auditory neurons. AB - Previous studies in the inferior colliculus have shown that spatial separation of signal and noise sources improves signal detection. In this study, we investigated the free-field unmasking response properties of single fibers in the auditory nerve--these were compared to those of inferior colliculus neurons under the same experimental conditions to test the hypothesis that central processing confers advantages for signal detection in the presence of spatially separated noise. For each neuron, we determined the detection threshold for a probe at the unit's best azimuth under three conditions: (1) by itself, (2) when a masker at a constant level was also presented at the unit's best azimuth, and (3) when the masker was positioned at different azimuths. We found that, on average, maskers presented at a unit's best azimuth elevated the probe detection threshold by 4.22 dB in the auditory nerve and 10.97 dB in the inferior colliculus. Angular separation of probe and masker sources systematically reduced the masking effect. The maximum masking release was on average 2.90 dB for auditory nerve fibers and 9.40 dB for inferior colliculus units. These results support the working hypothesis, suggesting that central processing contributes to the stronger free field unmasking in the inferior colliculus. PMID- 11778833 TI - Responses of medulla neurons to illumination and movement stimuli in the tiger beetle larvae. AB - Intracellular responses of medulla neurons (second-order visual interneurons) have been examined in the tiger beetle larva. The larva possesses six stemmata on either side of the head, two of which are much larger than the remaining four. Beneath the cuticle housing the stemmata an optic neuropil complex occurs consisting of lamina and medulla neuropils. Response patterns of medulla neurons to illumination and moving objects varied from neurons to neurons. For movement stimuli black discs and a black bar were moved in the rostro-caudal direction above the larva. Comparison of responses to the discs and the bar suggested a spatial summation of responses in some neurons, and tuning to small objects in some neurons. The majority of neurons responded to objects moving at heights of 10 mm and 50 mm with the same discharge pattern. A few neurons, however, showed distance sensitivities responding with an increase of spike discharges to moving objects only at either of the two heights. Such distance sensitivities still remained in one-stemma larvae, three of the four stemmata being occluded. These data are discussed in relation to distinct visual behavior of the larva and with special reference to perception of the hunting range. PMID- 11778834 TI - Structural correlates of mechanosensory transduction and adaptation in identified neurons of spider slit sensilla. AB - We used isolated but functionally intact preparations of the lyriform slit-sense organ VS-3 from the leg of the spider, Cupiennius salei Keys, to examine the role of prominent fine-structural elements for mechanosensory transduction and adaptation. Slit sensilla act as strain sensors in the cuticular exoskeleton; each slit is innervated by two mechanosensitive neurons. Punctate mechanical deformation at four points along the dendrites demonstrated that mechanical excitability is confined to membrane sites at the extreme dendrite tips that are enclosed by cuticular slit structures. Depletion of microtubules in VS-3 neurons by prolonged mechanical stimulation and application of 5 mmol l(-1) colchicine did not disrupt the generation of a receptor potential. Hence, putative gating mechanisms of the mechanically activated membrane channels at the dendrite tips appear to be largely independent of microtubular structures. The discrete adaptation pattern in each of the two partner neurons, rapidly adapting versus slowly adapting, did not depend on the distinct mode of dendrite attachment to cuticular slit structures, and even persisted in isolated neurons after their dendrite tips and auxiliary structures were lost. We suggest that the two discrete adaptation patterns are based on intrinsic differences in the action potential encoding process rather than differences in stimulus transformation or mechanotransduction. PMID- 11778835 TI - Asynchronous swimmeret beating during defense turns in the crayfish, Procambarus clarkii. AB - Swimmeret beating was monitored in freely moving specimens of the crayfish Procambarus clarkii as they exhibited defense turn responses to tactile stimuli. Analysis of videotape records revealed alterations in swimmeret beating during turning responses compared to straight, forward walking. During turns, swimmerets beat with shorter periods and smaller amplitude power strokes than during straight walking. Coordination between swimmerets also changed. Swimmerets on the side toward which the animal turned tended to lag behind their contralateral partners, rather than beat in synchrony as in straight walking, and ipsilateral coordination was loosened relative to straight walking. Asynchronous swimmeret beating accompanied asymmetric motions of the uropods in a manner similar to that observed during statocyst-dependent equilibrium reactions in P. clarkii, but removal of the statoliths did not eliminate turn-associated responses of the swimmerets. The coordinated action of the swimmerets and uropods may contribute to the torque that rotates the animal in the yaw plane. Implications of the observed changes in swimmeret coordination for understanding the underlying neuronal control system are discussed. PMID- 11778836 TI - Differential production of chirping behavior evoked by electrical stimulation of the weakly electric fish, Apteronotus leptorhynchus. AB - Aperonotus leptorhynchus (Gymnotiformes) produces wave-like electric organ discharges distinguished by a high degree of constancy. Transient frequency and amplitude modulations of these discharges occur both spontaneously and during social interactions, which can be mimicked by external electrical stimulation. The so-called chirps can be divided into four different types. Independent of the type of chirp produced under spontaneous conditions, the fish generate only significant numbers of type-2 chirps under evoked conditions. The rate of production of chirps of this type is largely determined by the frequency relative to the fish's frequency and signal intensity. Frequencies of + 10 Hz of the fish's own discharge frequency most effectively elicit chirps. Type-2 chirps can also be evoked through stimulation at or near the higher harmonic frequencies of the fish's frequency, but the chirp rate decreases with increasing number of the higher harmonic component. Over a certain range, the rate of production of type-2 chirps increases with increasing stimulus intensity. At very high intensities the generation of type-2 chirps is accompanied by the production of a novel type of electrical signal ("abrupt frequency rise") characterized by a frequency increase of approximately 20 Hz and high repetition rates of roughly 10 s(-1). We hypothesize that the different types of electric modulations subserve different behavioral functions. PMID- 11778837 TI - The biochemical properties and phylogenies of phosphofructokinases from extremophiles. AB - The enzyme phosphofructokinase (PFK) is a defining activity of the highly conserved glycolytic pathway, and is present in the domains Bacteria, Eukarya, and Archaea. PFK subtypes are now known that utilize either ATP, ADP, or pyrophosphate as the primary phosphoryl donor and share the ability to catalyze the transfer of phosphate to the 1-position of fructose-6-phosphate. Because of the crucial position in the glycolytic pathway of PFKs, their biochemical characteristics and phylogenies may play a significant role in elucidating the origins of glycolysis and, indeed, of metabolism itself. Despite the shared ability to phosphorylate fructose-6-phosphate, PFKs that have been characterized to date now fall into three sequence families: the PFKA family, consisting of the well-known higher eukaryotic ATP-dependent PFKs together with their ATP- and pyrophosphate-dependent bacterial cousins (including the crenarchaeal pyrophosphate-dependent PFK of Thermoprotetus tenax) and plant pyrophosphate dependent phosphofructokinases; the PFKB family, exemplified by the minor ATP dependent PFK activity of Escherichia coli (PFK 2), but which also includes at least one crenarchaeal enzyme in Aeropyrum pernix; and the tentatively named PFKC family, which contains the unique ADP-dependent PFKs from the euryarchaeal genera of Pyrococcus and Thermococcus, which are indicated by sequence analysis to be present also in the methanogenic species Methanococcus jannaschii and Methanosarcina mazei. PMID- 11778838 TI - Expression of the 2,4-D degradative pathway of pJP4 in an alkaliphilic, moderately halophilic soda lake isolate, Halomonas sp. EF43. AB - The broad host range plasmid pJP4, which carries genes for the degradation of 2,4 dichlorophenoxyacetic acid (2,4-D), 2-methyl-4-chlorophenoxyacetic acid, and 3 chlorobenzoic acid, was used in conjugation experiments with mixed cultures enriched from water and sediment samples from an alkaline pond in the area of Szegedi Feherto, a soda lake in south Hungary. pJP4-encoded mercury resistance was used as a selection marker. One of the transconjugants, the alkaliphilic, moderately halophilic strain EF43, stably maintained the plasmid and was able to degrade 2,4-D and 3-chlorobenzoate under alkaline conditions in the presence of an additional carbon source such as pyruvate, benzoate, or alpha-ketoglutarate, indicating that the degradative genes of pJP4 were expressed in this strain. However, it was unable to grow on these chloroaromatic substrates when the substrate was the sole source of carbon and energy. Chemostat cultivation experiments revealed that the 2,4-D degradation rate during growth on benzoate or pyruvate was limited by the low activity of chlorocatechol-degrading enzymes, particularly chloromuconate cycloisomerase. Strain EF43 was identified as Halomonas sp. on the basis of 16S rRNA sequencing and additional taxonomic studies. 16S rRNA sequence analysis revealed that strain EF43 is closely related to typical soda lake isolates belonging to the genus Halomonas. PMID- 11778840 TI - Characterization of pyridine nucleotide coenzymes in the hyperthermophilic archaeon Pyrococcus furiosus. AB - Pyridine-type nucleotides were identified in cell-free extracts of the hyperthermophilic archaeon Pyrococcus furiosus by their ability to replace authentic nicotinamide adenine dinucleotide (phosphate) [NAD(P)] in assays using pure P. furiosus enzymes. The nucleotides were purified using a combination of ion-exchange and reverse-phase chromatography. They were identified as NAD and NADP by analyses using liquid chromatography-mass spectrometry and high performance liquid chromatography. Their intracellular concentrations were measured in P. furiosus grown using maltose and peptides as the carbon sources. The concentrations decreased during the lag phase but remained constant during the exponential phase at approximately 0.17 and 0.13 mM, respectively. The amount of NAD was significantly lower (more than four-fold lower) than that in mesophilic bacteria, although the NADP concentration was comparable. The internal concentrations of NADH and NADPH in P. furiosus were determined to be 0.14 mM and 0.04 mM, respectively. The overall cellular concentration of NAD(P)(H) in P. furiosus (0.48 mM) is about half the value in the mesophiles. The NAD(H)/NADP(H) ratio in P. furiosus is consistent with the preferred use of NADP by several catabolic enzymes that have been purified from this organism. The mechanisms by which hyperthermophiles stabilize these thermally labile nicotinamide nucleotides are not known. PMID- 11778839 TI - Archaeology of Archaea: geomicrobiological record of Pleistocene thermal events concealed in a deep-sea subseafloor environment. AB - A record of the history of the Earth is hidden in the Earth's crust, like the annual rings of an old tree. From very limited records retrieved from deep underground, one can infer the geographical, geological, and biological events that occurred throughout Earth's history. Here we report the discovery of vertically shifted community structures of Archaea in a typical oceanic subseafloor core sample (1410 cm long) recovered from the West Philippine Basin at a depth of 5719 m. Beneath a surface community of ubiquitous deep-sea archaea (marine crenarchaeotic group I; MGI), an unusual archaeal community consisting of extremophilic archaea, such as extreme halophiles and hyperthermophiles, was present. These organisms could not be cultivated, and may be microbial relicts more than 2 million years old. Our discovery of archaeal rDNA in this core sample, probably associated with the past terrestrial volcanic and submarine hydrothermal activities surrounding the West Philippine Basin, serves as potential geomicrobiological evidence reflecting novel records of geologic thermal events in the Pleistocene period concealed in the deep-sea subseafloor. PMID- 11778841 TI - Isolation of Thermoanaerobacter keratinophilus sp. nov., a novel thermophilic, anaerobic bacterium with keratinolytic activity. AB - Several thermophilic anaerobic bacteria with keratinolytic activity growing at temperatures between 50 degrees C and 90 degrees C were isolated from samples collected on the island of Sao Miguel in the Azores (Portugal). On the basis of morphological, physiological, and 16S rDNA studies, the isolate 2KXI was identified as a new species of the genus Thermoanaerobacter, designated Thermoanaerobacter keratinophilus. This strain, which grows optimally at 70 degrees C, pH 7.0, and 0.5% NaCl, is the first member of the genus Thermoanaerobacter that has been described for its ability to degrade native keratin. Around 70% of native wool was solubilized after 10 days of incubation under anaerobic conditions. The strain was shown to possess intracellular and extracellular proteases optimally active at 60 degrees C, pH 7.0, and 85 degrees C, pH 8.0, respectively. Keratin hydrolysis was demonstrated in vitro using a sodium dodecyl sulfate gel containing feather meal. The extracellular protease responsible for breaking down keratin fibers was purified to homogeneity in only one step by applying hydroxyapatite column chromatography. The enzyme belongs to the serine-type proteases and has a molecular mass of 135 kDa. PMID- 11778842 TI - Optical chamber system designed for microscopic observation of living cells under extremely high hydrostatic pressure. AB - A novel pressure chamber system has been developed for the study of living cells under conditions of extremely high hydrostatic pressure up to 100 MPa (1 atm = 0.101325 MPa). The temperature in the chamber is thermostatically controlled in the range from 2 degrees to 80 degrees C. Two high-pressure pumps are employed for continuous perfusion of the chamber with culture medium and a chemical solution under high hydrostatic pressure conditions. The chamber has a 2-mm-thick glass window 2 mm in diameter, with a minimum working distance of 3.8 mm. The chamber system is designed to be adaptable to a variety of microscopic and imaging techniques. Using this chamber system, we successfully carried out real time observations of elongated Escherichia coli and rounded HeLa cells under pressure. PMID- 11778843 TI - Contribution of Hsc70 to barotolerance in the yeast Saccharomyces cerevisiae. AB - The contribution of Hsc70 to barotolerance in logarithmic-phase cells of the HSC70 (ssb1 and ssb2) deletion mutant and in strains expressing the HSC70 gene on either a low- or a high-copy-number plasmid was studied. The deletion-mutant strain had higher thermotolerance and a slightly lower barotolerance than the control strain. The strain that expresses the HSC70 gene in high copy number had a higher barotolerance than the strain that expresses the gene in low copy number. These results suggest that Hsc70 contributes to barotolerance during exponentially growing conditions as does Hsp104 during heat-shock treatment. PMID- 11778844 TI - A catalase-peroxidase from a newly isolated thermoalkaliphilic Bacillus sp. with potential for the treatment of textile bleaching effluents. AB - A new thermoalkaliphilic bacterium was isolated from a textile wastewater drain and identified as a new Bacillus sp. (Bacillus SF). Because of its high pH stability and thermostability, a catalase-peroxidase (CP) from this strain has potential for the treatment of textile bleaching effluents. The CP from Bacillus SF was purified to more than 70.3-fold homogeneity using fractionated ammonium sulfate precipitation, hydrophobic interaction, and anion-exchange and gel filtration chromatography. The native CP had a molecular mass of 165 kDa and was composed of two identical subunits. The isoelectric point of the protein was at pH 6.0. Peptide mass mapping using matrix-assisted laser desorption ionization mass spectrometry showed a homology between the CP from Bacillus SF and the CP from Bacillus stearothermophilus. The apparent Km value of the catalase activity for H2O2 was 2.6 mM and the k(cat) value was 11,475 s(-1). The enzyme showed high catalase activity and an appreciable peroxidase activity with guaiacol and o dianisidine. The enzyme was stable at high pH, with a half-life of 104 h at pH 10 and 25 degrees C and 14 h at 50 degrees C. The enzyme was inhibited by azide and cyanide, in a competitive manner, but not by the catalase-specific inhibitor 3 amino-1,2,4-triazole. PMID- 11778845 TI - Using flow cytometry to follow the apoptotic cascade. AB - Flow cytometry has been extensively used to follow the apoptotic cascade and to enumerate apoptotic cells, both in cell cultures and, to a lesser extent, in tissue biopsies. An overview of the apoptotic cascade and how flow cytometric measurements can be used to observe the different elements of this process is presented. PMID- 11778846 TI - Regulatory roles of thioredoxin in oxidative stress-induced cellular responses. AB - Thioredoxin (TRX) is a small ubiquitous and multifunctional protein having a redox-active dithiol/disulfide within the conserved active site sequence -Cys-Gly Pro-Cys-. TRX is induced by a variety of oxidative stimuli, including UV irradiation, inflammatory cytokines and chemical carcinogens, and has been shown to play crucial roles in the regulation of cellular responses such as gene expression, cell proliferation and apoptosis. Overexpression of TRX protects cells from cytotoxicity elicited by oxidative stress in both in vitro and in vivo models. The regulatory mechanism of TRX expression and activity is also being elucidated. Recently, TRX binding protein-2 (TBP-2)/vitamin D3 up-regulated protein 1 (VDUP1) was identified as a negative regulator of TRX. The analysis of TRX promoter region has revealed putative regulatory elements responsible for oxidative stress. Thus, the modulation of TRX functions may be a new therapeutic strategy for the treatment of oxidative stress-mediated diseases. PMID- 11778847 TI - Role of nitric oxide in a progressive neurodegeneration model of Parkinson's disease in the rat. AB - This study was undertaken to investigate the nitric oxide synthase (NOS) activity in the striatum following 6-hydroxydopamine (6-OHDA) induced neurodegeneration in rats. Constitutive NOS (cNOS) activity remained unaltered at 3, 7 and 14 days after lesion, while a 43% and 45% decrease was observed at 30 and 50 days, respectively. Inducible NOS (iNOS) activity was detected only on the 3rd day after lesion and not in subsequent days or the control striatum. N(G)-nitro-L arginine methyl ester (L-NAME) pretreatment blocked the amphetamine-induced rotations and inhibited the iNOS activity at the 3rd day after the 6-OHDA injection. L-NAME pretreatment also significantly restored the striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in 6 OHDA treated rats. Thus a possible role of nitric oxide in 6-OHDA induced neurodegeneration is suggested. PMID- 11778848 TI - Oxidative stress in haemodialysis--intradialytic changes. AB - Oxidative stress is likely to be involved in the development of complications due to haemodialysis. Though there is evidence for production of oxygen free radicals during haemodialysis, reports on net oxidative imbalance due to a single dialysis session are conflicting. Hence, a time-course analysis of changes in lipid peroxides (LPO) along with antioxidant enzymes and vitamins was carried out. Hourly changes in LPO and antioxidants were studied during a first-use cuprophan membrane and acetate dialysis in 20 patients on regular haemodialysis treatment. Data were corrected for haemoconcentration and standardised to measure the rate of change before statistical evaluation using analysis of variance for repeated measures. The results of the study showed a net oxidative stress due to a single dialysis session in the form of increased plasma and erythrocyte lipid peroxidation, decrease in plasma vitamin E, slight increase in plasma superoxide dismutase and erythrocyte glutathione peroxidase and no change in plasma glutathione peroxidase. erythrocyte superoxide dismutase and plasma vitamin A levels. The oxygen radical production was found to be maximum in the first hour of dialysis. PMID- 11778849 TI - Differential antioxidant responses to norflurazon-induced oxidative stress in maize. AB - This study examined the contribution of catalase (CAT) and superoxide dismutase (SOD) in the overall antioxidant response to norflurazon (NF)-induced oxidative stress in leaves, mesocotyls and scutella of maize (Zea mays). Maize catalase null mutants were used to provide insights into the role(s) of these isozymes. A substantial increase in Cat1 and Cat2 transcript levels occurred in NF-treated leaves in all maize lines examined. However, these two transcripts did not show a particular pattern of change in NF-treated scutella from 5-day postimbibition (dpi) and 18-day postpollination (dpp) maize. The NF-induced increase in Cat1 appeared to be dependent on excessive light energy caused by a lack of photoprotectant carotenoids. especially in leaves. In NF-treated leaves, the chloroplastic Cu/Zn-SOD-1 isozyme responded strongly compared to the cytosolic Cu/Zn-SOD and mitochondrial Mn-SOD-3 isozymes, suggesting the critical role of SOD-1 as a major component in chloroplastic antioxidant defenses. All SOD isozymes in the NF-treated scutella of various maize lines were consistent in their response to NF. The most significant increase was observed with Sod1 in NF treated leaves; however, no significant Sod1 changes were observed in similarly treated scutella at 5 dpi and 18 dpp. These results suggest that the response of the Cat and Sod genes to NF is likely developmental and tissue-specific. PMID- 11778850 TI - Ultraviolet irradiation of titanium dioxide in aqueous dispersion generates singlet oxygen. AB - We previously reported that irradiation of titanium dioxide (TiO2) in ethanol generates both singlet oxygen (1O2) and superoxide anion (O2*-) as measured by EPR spectroscopy. The present study describes the production of reactive oxygen species upon irradiation of TiO2 in aqueous suspension as determined by EPR spectroscopy using 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TMP) and 5,5-dimethyl pyrroline-N-oxide (DMPO). Photoproduction of 1O2 by suspended TiO2, detected as 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (4-oxo-TEMPO), was measured in water and deuterium oxide (D2O) in the presence or absence of sodium azide (NaN3) and under air or argon atmospheres. Production of a DMPO-OH adduct was examined in 4-oxo TMP containing medium in the presence or absence of dimethyl sulfoxide (DMSO). The signal for the DMPO spin adduct of superoxide anion was not observed in aqueous conditions. Kinetic analysis revealed that 1O2 was produced at the surface of irradiated TiO2 in aqueous suspension as was observed in ethanol. Kinetic analysis revealed that the formation of DMPO-OH adduct reflects oxidation of DMPO by 1O2 rather than the trapping of the hydroxyl radical produced by the reaction of photo-exited TiO2 and water. The production of large amounts of 1O2 by TiO2 in aqueous suspension as compared to those in ethanol and possible formation of hydroxyl radical in aqueous suspension but not in alcohol, suggest that irradiation of TiO2 in aqueous environments is biologically more important than that in non-aqueous media. PMID- 11778851 TI - Alpha-lipoic acid and alpha-lipoamide prevent oxidant-induced lysosomal rupture and apoptosis. AB - Alpha-lipoic acid (LA) and its corresponding derivative, alpha-lipoamide (LM), have been described as antioxidants, but the mechanisms of their putative antioxidant effects remain largely uncharacterised. The vicinal thiols present in the reduced forms of these compounds suggest that they might possess metal chelating properties. We have shown previously that cell death caused by oxidants may be initiated by lysosomal rupture and that this latter event may involve intralysosomal iron which catalyzes Fenton-type chemistry and resultant peroxidative damage to lysosomal membranes. Here, using cultured J774 cells as a model, we show that both LA and LM stabilize lysosomes against oxidative stress, probably by chelating intralysosomal iron and, consequently, preventing intralysosomal Fenton reactions. In preventing oxidant-mediated apoptosis, LM is significantly more effective than LA, as would be expected from their differing capacities to enter cells and concentrate within the acidic lysosomal compartment. As previously reported, the powerful iron-chelator, desferrioxamine (Des) (which also locates within the lysosomal compartment), also provides protection against oxidant-mediated cell death. Interestingly, although Des enhances the partial protection afforded by LA, it confers no additional protection when added with LM. Therefore, the antioxidant actions of LA and LM may arise from intralysosomal iron chelation, with LM being more effective in this regard. PMID- 11778852 TI - Dental materials: troubling trends. PMID- 11778853 TI - Dentin bonding. PMID- 11778854 TI - Clinical use of an intraoral silicoating technique. AB - A ceramic fracture rate of metal-ceramic fixed prosthodontics of up to almost 9% calls for an efficient and effective intraoral repair system. For the repair of fractured veneering material, an intraoral silicoating technique was introduced. In contrast to other repair techniques, the silicoating can successfully be used on a variety of dental restorative materials and, therefore, offers additional applications in the field of the intraoral adhesive technique. This silicoating technique, consisting of a chairside airabrasion device filled with a specific silica-coated air-abrasion medium, has been used intraorally by the authors since 1993 for clinical purposes. The clinical procedure is described for different applications in the field of the adhesive technique: intraoral repair, preconditioning of core buildups, implant abutments, and surfaces of fixed prosthodontics for the bonding of orthodontic brackets or periodontal splints. CLINICAL SIGNIFICANCE: The intraoral silicoating technique promotes reliable adhesion to the major part of metal alloy, composite, and ceramic surfaces of fixed prosthodontics. Preliminary clinical results of intraoral repairs conducted with this technique have shown that it presents a medium-term alternative to the replacement of the restoration. Also, the preliminary results of the clinical applications in other fields of adhesive dentistry are promising. PMID- 11778855 TI - Nightguard vital bleaching: a long-term study on efficacy, shade retention. side effects, and patients' perceptions. AB - BACKGROUND: The scientific literature is lacking in long-term clinical data on the duration of efficacy and post-treatment side effects of nightguard vital bleaching. PURPOSE: This longitudinal clinical study was undertaken (1) to determine the clinical efficacy and duration of efficacy at 3, 6, and 47 months post treatment of a peroxide-containing whitening solution; (2) to evaluate safety issues with respect to using a peroxide whitening solution; and (3) to determine patients' perceptions of the whitening technique. MATERIALS AND METHODS: This project was part of a nightguard vital bleaching study involving human participants. The study teeth for efficacy and duration of efficacy when using a 10% carbamide peroxide solution were the four maxillary central and lateral incisors, with the tooth shade being taken from the middle third of the tooth. Safety issues evaluated were the changes in gingival index (GI), plaque index (PI), nonmarginal gingival index (NMGI), nongingival oral mucosal index (NGOMI), and tooth vitality (TV). Radiographic changes of the study teeth and the patients' perceptions of tooth sensitivity (TS) or gingival irritation (Girr) during treatment and post treatment were also evaluated. RESULTS: The active 10% carbamide peroxide whitening solution used in this study was effective in lightening teeth (98%), and this effect was sustained at a mean of 47 months post treatment in 82% of the participants. When evaluating safety issues, 66% of the participants using the active solution reported TS or Girr. No one reported TS or Girr or any other adverse effects at the end of the study. CONCLUSIONS: The results of this study concur with those of previously reported studies that nightguard vital bleaching using a 10% carbamide peroxide whitening solution according to the manufacturer's instructions is efficacious and safe, with minimal side effects. In addition, long-term shade retention was reported by 82% of the participants at the end of the study, with no adverse side effects. CLINICAL SIGNIFICANCE: Results of this study should reassure dentists that nightguard vital bleaching is a safe, effective, and predictable method to lighten teeth. The whitening effect lasted up to 47 months in 82% of the patients, with no adverse side effects reported at the end of the study. PMID- 11778856 TI - Effect of light-enhanced bleaching on in vitro surface and intrapulpal temperature rise. AB - PURPOSE: This study investigated the effect of the presence, absence, and aging of a heat-enhancing compound (colorant) added to bleaching gel on the temperature rise of the gel itself, as well as the temperature rise within the pulp chamber, when a tooth was exposed to a variety of light-curing units in vitro. MATERIALS AND METHODS: An extracted human upper central incisor was fitted with thermocouples placed in the pulp chamber as well as on the facial tooth surface. A temperature-controlled simulated intrapulpal fluid flow was provided to the tooth, and bleaching agent (Opalesence XTRA, Ultradent) containing heat-enhancing colorant, aged colorant, or no colorant was applied to the facial surface. The tooth and light-curing unit were placed in a thermostatically controlled oven at 37 degrees C, and real-time gel and intrapulpal temperature values were recorded digitally. Light-curing units used were a plasma arc light (PAC) (PowerPac, ADT), a conventional quartz tungsten halogen source (QTH) (Optilux 501, Demetron/Kerr), the QTH light used in high-power (bleaching) mode, and an argon ion laser (AccuCure 3000, LaserMed). An exposure scenario simulating light-enhanced bleaching of 10 upper teeth was developed. Temperature rise over the pre exposure, baseline value associated with the last light exposure in the bleaching sequence was calculated for each curing and bleaching combination. Five replications for each test condition were made. Temperature rise values were compared using analysis of variance (ANOVA) at a preset alpha of 0.05. RESULTS: When fresh colorant-containing bleach was used, the PAC light increased bleach temperature 39.3 degrees C above baseline. With no added colorant, temperature rise was 37.1 degrees C. The QTH light in bleach mode resulted in gel temperature 24.8 degrees C above baseline, whereas the temperature increase was only 11.5 degrees C when no colorant was used. Conventional QTH light use increased fresh bleach temperature by 17.7 degrees C, whereas an increase of only 11.1 degrees C was measured without colorant. The argon ion laser produced equivalent temperature rise regardless of the presence or freshness of the colorant, approximately 9.4 degrees C. Intrapulpal temperatures were all significantly lower than those recorded in the bleaching gel and ranged from 5 degrees to 8 degrees C. As a rule, the presence of fresh heat-enhancing colorant in the bleaching gel resulted in a significant intrapulpal temperature increase (approximately 1 degrees C) over that reached using other lights. The PAC and the QTH light used in bleach mode induced greater intrapulpal temperature rise than the laser. CLINICAL SIGNIFICANCE: Freshness of bleaching agent incorporating light-activated, heat-enhancing colorant influences temperature rise of bleaching gel and also may increase intrapulpal temperature values. Use of intense lights does elevate bleach temperature and also results in increased intrapulpal temperature that may further impact on patient sensitivity and pulpal health resulting from this treatment. PMID- 11778857 TI - Tensile bond strengths of fourth- and fifth-generation dentin adhesives with packable resin composites. AB - PURPOSE: Placement of packable composites would be simplified if a single-bottle dentin bonding agent, rather than the more complex, multiple-bottle dentin bonding agents, involving multiple steps, could be used successfully with adequate bond strength. This study was designed to compare the tensile bond strengths to extracted human dentin of four single-bottle (fifth-generation) and four multiple-bottle (fourth-generation) dentin bonding agents with four packable composites. MATERIALS AND METHODS: Packable composites (P60, 3M Dental Products Division; ALERT, Jeneric-Pentron; Pyramid Dentin, Bisco; and Clearfil AP-X, Kuraray America) were tested for in vitro tensile bond strength to human dentin with their single-bottle and their multiple-bottle dentin bonding agents. Bond strengths were measured using a truncated cone tensile test, with a bonding diameter of 3 mm, after storage of specimens in water at 37 degrees C and 100% relative humidity for 24 hours, and using a testing machine at a crosshead speed of 0.5 mm per minute. RESULTS: Means and standard deviations (n = 10) of tensile bond strengths (MPa) for the single-bottle system were P60, 21.3 MPa (6.7); ALERT, 26.6 MPa (4.2); Pyramid Dentin, 14.8 MPa (4.4); and Clearfil AP-X, 18.6 MPa (3.7). For the multiple-bottle system they were P60, 20.0 MPa (8.6); ALERT, 20.6 MPa (6.2); Pyramid Dentin, 16.0 MPa (3.4); and Clearfil AP-X, 17.8 MPa (6.0). Two-way analysis of variance showed significant differences among composites but no significant differences between single-bottle and multiple bottle bonding agents. The Tukey-Kramer interval (p < .05) for comparisons of bond strengths among composites was 4.8 MPa. CONCLUSIONS: For single-bottle agents, bond strengths were ranked as ALERT > P60, P60 = Clearfil, P60 > Pyramid, and Clearfil = Pyramid. For multiple-bottle agents, there were no significant differences in bond strengths among the composites. CLINICAL SIGNIFICANCE: Single bottle bonding agents provide similar in vitro bond strengths for use with packable composites as do the same manufacturers' multiple-bottle bonding agents. PMID- 11778864 TI - Composite bonding. PMID- 11778865 TI - Bioinformatic tools for DNA/protein sequence analysis, functional assignment of genes and protein classification. AB - The development of efficient DNA sequencing methods has led to the achievement of the DNA sequence of entire genomes from (to date) 55 prokaryotes, 5 eukaryotic organisms and 10 eukaryotic chromosomes. Thus, an enormous amount of DNA sequence data is available and even more will be forthcoming in the near future. Analysis of this overwhelming amount of data requires bioinformatic tools in order to identify genes that encode functional proteins or RNA. This is an important task, considering that even in the well-studied Escherichia coli more than 30% of the identified open reading frames are hypothetical genes. Future challenges of genome sequence analysis will include the understanding of gene regulation and metabolic pathway reconstruction including DNA chip technology, which holds tremendous potential for biomedicine and the biotechnological production of valuable compounds. The overwhelming volume of information often confuses scientists. This review intends to provide a guide to choosing the most efficient way to analyze a new sequence or to collect information on a gene or protein of interest by applying current publicly available databases and Web services. Recently developed tools that allow functional assignment of genes, mainly based on sequence similarity of the deduced amino acid sequence, using the currently available and increasing biological databases will be discussed. PMID- 11778866 TI - Biotechnology and genetics of ergot alkaloids. AB - Ergot alkaloids, i.e. ergoline-derived toxic metabolites, are produced by a wide range of fungi, predominantly by members of the grass-parasitizing family of the Clavicipitaceae. Naturally occurring alkaloids like the D-lysergic acid amides, produced by the "ergot fungus" Claviceps purpurea, have been used as medicinal agents for a long time. The pharmacological effects of the various ergot alkaloids and their derivatives are due to the structural similarity of the tetracyclic ring system to neurotransmitters such as noradrenaline, dopamine or serotonin. In addition to "classical" indications, e.g. migraine or blood pressure regulation, there is a wide spectrum of potential new applications of this interesting group of compounds. The biotechnology of ergot alkaloids has a long tradition, and efficient parasitic and submerse production processes have been developed; the biochemistry of the pathway and the physiology of production have been worked out in detail. The recent identification of a cluster of genes involved in ergot alkaloid biosynthesis in C. purpurea and the availability of molecular genetic techniques allow the development of strategies for rational drug design of ergoline-related drugs by enzyme engineering and by biocombinatorial approaches. PMID- 11778867 TI - Current status of the anticoagulant hirudin: its biotechnological production and clinical practice. AB - Hirudin is a potent thrombin inhibitor originally derived from the medicinal leech, Hirudo medicinalis. Owing to its high affinity and specificity for thrombin, hirudin has been intensively investigated for research and therapeutic purposes. The investigation of hirudin has contributed greatly to the understanding of the mode of action of thrombin and the clotting system. Hirudin and several hirudin analogues have also been demonstrated to have several advantages as a highly specific anticoagulant over the most widely used drug, heparin. Due to the great demand for hirudin in physicochemical and clinical studies, various recombinant systems have been developed, using bacteria, yeasts, and higher eukaryotes, to obtain the biologically active hirudin in significant quantities. After 10 years of clinical applications, two recombinant hirudins and a hirudin analogue have gained marketing approval from the United States Food and Drug Administration, for several applications. Clinical trials are currently ongoing for other treatments for thrombotic disease. As a consequence, it is conceivable that hirudin may expand its therapeutic utility over heparin in the near future. PMID- 11778868 TI - Antigiardial drugs. AB - Giardia intestinalis is a world-wide cause of intestinal infection. Treatment of this debilitating disease is usually accomplished using one of several drugs. Metronidazole is the treatment of choice, but benzimidazoles are now being used more frequently. Other treatments include quinacrine, paromomycin and furazolidone. Even though these drugs are all used to treat the same disease, their modes of action differ in all cases. However, resistance is increasing and new alternatives are being sought. New wave antigiardials all appear to have their roots in natural herbal remedies. This mini-review looks at the current treatments available, their efficacy, side effects and different modes of action and addresses a possible way forward using natural products. PMID- 11778869 TI - Microbial transformations of 2-substituted benzothiazoles. AB - The occurrence of benzothiazoles in the environment seems to be restricted to aquatic compartments and is mainly associated with the manufacture and use of the rubber additive 2-mercaptobenzothiazole (MBT) and its derivatives. Although data on benzothiazole biotransformations in natural environments at ppb and ppt levels are scarce, the unsubstituted benzothiazole (BT) and 2-hydroxybenzothiazole (OBT) are generally considered to be biodegradable, whereas 2-methylthiobenzothiazole is recalcitrant. The fungicide 2-thiocyanomethylthiobenzothiazole is assumed to be hydrolysed to MBT, which is then further methylated. At higher concentration levels, similar conclusions can generally be drawn. In addition, BT, MBT, 2 aminobenzothiazole and benzothiazole-2-sulphonate can be biodegraded, although side- and end-products may form. For BT and MBT, threshold concentration were reported above which inhibitory effects on biological treatment processes occur. Due to the limited availability of axenic bacterial cultures capable of benzothiazole mineralization, only the initial steps of the degradation pathways have been elucidated so far. PMID- 11778870 TI - Continuous lactic acid fermentation using a plastic composite support biofilm reactor. AB - An immobilized-cell biofilm reactor was used for the continuous production of lactic acid by Lactobacillus casei subsp. rhamnosus (ATCC 11443). At Iowa State University, a unique plastic composite support (PCS) that stimulates biofilm formation has been developed. The optimized PCS blend for Lactobacillus contains 50% (wt/wt) agricultural products [35% (wt/wt) ground soy hulls, 5% (wt/wt) soy flour, 5% (wt/wt) yeast extract, 5% (wt/wt) dried bovine albumin, and mineral salts] and 50% (wt/wt) polypropylene (PP) produced by high-temperature extrusion. The PCS tubes have a wall thickness of 3.5 mm, outer diameter of 10.5 mm, and were cut into 10-cm lengths. Six PCS tubes, three rows of two parallel tubes, were bound in a grid fashion to the agitator shaft of a 1.2-1 vessel for a New Brunswick Bioflo 3000 fermentor. PCS stimulates biofilm formation, supplies nutrients to attached and suspended cells, and increases lactic acid production. Biofilm thickness on the PCS tubes was controlled by the agitation speed. The PCS biofilm reactor and PP control reactor achieved optimal average production rates of 9.0 and 5.8 g l(-1) h(-1), respectively, at 0.4 h(-1) dilution rate and 125 rpm agitation with yields of approximately 70%. PMID- 11778871 TI - Potential inhibitors from wet oxidation of wheat straw and their effect on growth and ethanol production by Thermoanaerobacter mathranii. AB - Alkaline wet oxidation (WO) (using water, 6.5 g/l sodium carbonate, and 12 bar oxygen at 195 degrees C) was used for pre-treating wheat straw (60 g/l), resulting in a hemicellulose-rich hydrolysate and a cellulose-rich solid fraction. The hydrolysate consisted of soluble hemicellulose (9 g/l), aliphatic carboxylic acids (6 g/l), phenols (0.27 g/l or 1.7 mM), and 2-furoic acid (0.007 g/l). The wet-oxidized wheat straw hydrolysate caused no inhibition of ethanol yield by the anaerobic thermophilic bacterium Thermoanaerobacter mathranii. Nine phenols and 2-furoic acid, identified to be present in the hydrolysate, were each tested in concentrations of 10-100x the concentration found in the hydrolysate for their effect on fermentation by T. mathranii. At 2 mM, these aromatic compounds were not inhibitory to growth or ethanol yield in T. mathranii. When the concentration of aromatics was increased to 10 mM, the fermentation was severely inhibited by the phenol aldehydes and to a lesser extent by the phenol ketones. By adding the same aromatic compounds to WO hydrolysate (10 mM), synergistic inhibitory effects of all tested compounds with hydrolysate components were shown. When the hydrolysate was concentrated three- and six-fold, growth and fermentation with T. mathranii were inhibited. At a six-fold hydrolysate concentration, the total concentration of phenolic monomers was 17 mM; hence aromatic monomers are an important co-factor in hydrolysate inhibition. PMID- 11778872 TI - Modelling and optimization of environmental conditions for kefiran production by Lactobacillus kefiranofaciens. AB - A mathematical model for kefiran production by Lactobacillus kefiranofaciens was established, in which the effects of pH, substrate and product on cell growth, exopolysaccharide formation and substrate assimilation were considered. The model gave a good representation both of the formation of exopolysaccharides (which are not only attached to cells but also released into the medium) and of the time courses of the production of galactose and glucose in the medium (which are produced and consumed by the cells). Since pH and both lactose and lactic acid concentrations differently affected production and growth activity, the model included the effects of pH and the concentrations of lactose and lactic acid. Based on the mathematical model, an optimal pH profile for the maximum production of kefiran in batch culture was obtained. In this study, a simplified optimization method was developed, in which the optimal pH profile was determined at a particular final fermentation time. This was based on the principle that, at a certain time, switching from the maximum specific growth rate to the critical one (which yields the maximum specific production rate) results in maximum production. Maximum kefiran production was obtained, which was 20% higher than that obtained in the constant-pH control fermentation. A genetic algorithm (GA) was also applied to obtain the optimal pH profile; and it was found that practically the same solution was obtained using the GA. PMID- 11778873 TI - High-efficiency synthesis of oligosaccharides with a truncated beta-galactosidase from Bifidobacterium bifidum. AB - An exceptionally large beta-galactosidase, BIF3, with a subunit molecular mass of 188 kDa (1,752 amino acid residues) was recently isolated from Bifidobacterium bifidum DSM20215 [Moller et al. (2001) Appl Environ Microbiol 67:2276-2283]. The BIF3 polypeptide comprises a signal peptide followed by an N-terminal beta galactosidase region and a C-terminal galactose-binding motif. We have investigated the functional importance of the C-terminal part of the BIF3 sequence by deletion mutagenesis and expression of truncated enzyme variants in Escherichia coli. Deletion of approximately 580 amino acid residues from the C terminal end converted the enzyme from a normal, hydrolytic beta-galactosidase into a highly efficient, transgalactosylating enzyme. Quantitative analysis showed that the truncated beta-galactosidase utilised approximately 90% of the reacted lactose for the production of galacto-oligosaccharides, while hydrolysis constituted a 10% side reaction. This 9:1 ratio of transgalactosylation to hydrolysis was maintained at lactose concentrations ranging from 10% to 40%, implying that the truncated beta-galactosidase behaved as a "true" transgalactosylase even at low lactose concentrations. PMID- 11778874 TI - A novel thermostable branching enzyme from an extremely thermophilic bacterial species, Rhodothermus obamensis. AB - A branching enzyme (EC 2.4.1.18) gene was isolated from an extremely thermophilic bacterium, Rhodothermus obamensis. The predicted protein encodes a polypeptide of 621 amino acids with a predicted molecular mass of 72 kDa. The deduced amino acid sequence shares 42-50% similarity to known bacterial branching enzyme sequences. Similar to the Bacillus branching enzymes, the predicted protein has a shorter N terminal amino acid extension than that of the Escherichia coli branching enzyme. The deduced amino acid sequence does not appear to contain a signal sequence, suggesting that it is an intracellular enzyme. The R. obamensis branching enzyme was successfully expressed both in E. coli and a filamentous fungus, Aspergillus oryzae. The enzyme showed optimum catalytic activity at pH 6.0-6.5 and 65 degrees C. The enzyme was stable after 30 min at 80 degrees C and retained 50% of activity at 80 degrees C after 16 h. Branching activity of the enzyme was higher toward amylose than toward amylopectin. This is the first thermostable branching enzyme isolated from an extreme thermophile. PMID- 11778875 TI - Sequence of celQ and properties of celQ, a component of the Clostridium thermocellum cellulosome. AB - The nucleotide sequence of the Clostridium thermocellum F1 celQ gene, which codes for the endoglucanase CelQ, consists of 2,130 bp encoding 710 amino acids. The precursor form of CelQ has a molecular weight of 79,809 and is composed of a signal peptide, a family 9 cellulase domain, a family IIIc carbohydrate-binding module (CBM), and a dockerin domain. Truncated derivatives of CelQ were constructed: CelQdeltadoc consisted of the catalytic domain and the CBM; CelQcat consisted of the catalytic domain only. CelQdeltadoc showed strong activity toward carboxymethylcellulose (CMC) and barley beta-glucan and low activity toward Avicel, acid-swollen cellulose, lichenan, and xylan. The Vmax and Km values were 235 micromol/min/mg and 3.3 mg/ml, respectively, for CMC. By contrast, CelQcat, which was devoid of the CBM, showed negligible activity toward CMC, i.e., about 1/1,000 of the activity of CelQdeltadoc, supporting the previously proposed idea that family IIIc CBMs participate in the catalytic function of the enzyme. Immunological analysis using an antiserum raised against CelQdeltadoc confirmed that CelQ is a component of the C. thermocellum cellulosome. PMID- 11778876 TI - Metabolic redirection of carbon flow toward isoleucine by expressing a catabolic threonine dehydratase in a threonine-overproducing Corynebacterium glutamicum. AB - Carbon destined for lysine synthesis in Corynebacterium glutamicum ATCC 21799 can be diverted toward threonine by overexpression of genes encoding a feedback insensitive homoserine dehydrogenase (hom(dr)) and homoserine kinase (thrB). We studied the effects of introducing two different threonine dehydratase genes into this threonine-producing system to gauge their effects on isoleucine production. Co-expression of hom(dr), thrB, and ilvA, which encodes a native threonine dehydratase, caused isoleucine to accumulate to a final concentration of 2.2+/ 0.2 g l(-1), five-fold more than accumulates in the wild-type strain, and approximately twice as much as accumulates in the strain expressing only hom(dr) and thrB. Comparing these data with previous results, we found that overexpression of the three genes, hom(dr), thrB, and ilvA, in C. glutamicum ATCC 21799 is no better in terms of isoleucine production than the expression of a single gene, tdcB, encoding a catabolic threonine dehydratase from Escherichia coli. Co-expression of hom(dr), thrB, and tdcB, however, caused the concentration of isoleucine to increase 20-fold compared to the wild-type strain, about four times more than the corresponding ilvA-expressing strain. In this system, the apparent yield of isoleucine production was multiplied by a factor of two [2.1 mmol (g dry cell weight)(-1)]. While the balance of excreted metabolites showed that the carbon flow in this strain was completely redirected from the lysine pathway into the isoleucine pathway, it also showed that more pyruvate was diverted into amino acid synthesis. PMID- 11778877 TI - An improved procedure for production of human epidermal growth factor from recombinant E. coli. AB - An improved procedure for the fermentation and purification of human epidermal growth factor (hEGF) was developed. Recombinant Escherichia coli HB-101 [lacUV5omp08hEGF] harboring plasmid lacUV5omp08hEGF encoding hEGF was used in fermentation to increase levels of hEGF. Medium composition, and the levels of inoculum, inducer (isopropyl-beta-D-thiogalactoside) and ampicillin were optimized with respect to volumetric fermentation of hEGF. As a result, the hEGF concentration reached a high value of 242 mg l(-1) and the amount of heterogeneous protein decreased by 62% compared with that before optimization in batch fermentation. High-quality hEGF was purified from the fermentation culture by centrifugation, salting-out, resuspension, recentrifugation and finally gel chromatography on a Grad-iFrac System using Sephadex G-50 superfine. The purity of hEGF and the total yield were more than 94% and higher than 36%, respectively, and SDS-PAGE of the purified hEGF demonstrated a single band corresponding to an hEGF standard. In particular, a very important phenomenon was found, i.e. that the amount of heterogenous protein in fermentation broths cultured in media with high concentrations of lactose is far less than that cultured in media with high concentrations of glucose. PMID- 11778878 TI - Cloning and characterization of genes from Agrobacterium sp. IP I-671 involved in hydantoin degradation. AB - Cloning and sequencing of a 7.1 kb DNA fragment from Agrobacterium sp IP I-671 revealed seven open reading frames (ORFs) encoding D-hydantoinase, D-carbamoylase and putative hydantoin racemase, D-amino acid oxidase and NAD(P)H-flavin oxidoreductase. Two incomplete ORFs flanking the hydantoin utilization genes showed similarities to genes involved in transposition. Expression of the D hydantoinase and D-carbamoylase gene in Escherichia coli gave mainly inactive protein concentrated in inclusion bodies, whereas homologous expression on an RSF1010 derivative increased hydantoinase and D-carbamoylase activity 2.5-fold and 10-fold, respectively, in this strain. Inactivation of the D-carbamoylase gene in Agrobacterium sp IP I-671 led to a complete loss of detectable carbamoylase activity whereas the low hydantoinase activity remaining after inactivation of the D-hydantoinase gene indicated the presence of a second hydantoinase-encoding gene. Two plasmids of 80 kb and 190 kb in size were identified by pulsed-field gel electrophoresis and the cloned hydantoin utilization genes were found to be localized on the 190 kb plasmid. PMID- 11778879 TI - Effects of transcription induction homogeneity and transcript stability on expression of two genes in a constructed operon. AB - A synthetic operon was constructed using the reporter genes gfp and lacZ and the arabinose-inducible araBAD promoter. DNA cassettes encoding mRNA secondary structures were placed at the 3' and 5' ends of the genes and a putative RNase E site was placed between the genes. These mRNA control elements have been shown to affect transcript processing and decay, resulting in altered protein levels. These constructs were transformed into cells harboring the native arabinose inducible araE gene encoding the arabinose transport protein and engineered cells harboring a constitutively expressed araE. In the strains with arabinose dependent transport the linear response in the production of both reporter proteins to inducer concentration occurred over a narrow range of arabinose concentrations. In the strains with constitutive transport the linear range of gene expression occurred over a much larger arabinose concentration range than in strains with the arabinose-inducible transport. Strains with the arabinose inducible transport harboring different operon constructs produced the two reporter proteins at very different levels at low arabinose concentrations; as inducer concentrations increased, differences in relative expression levels decreased. In contrast, strains with constitutive transport harboring different operon constructs produced the reporter proteins at very different levels across the entire range of inducer concentrations, pointing to the importance of optimizing gene expression control at various levels to control the production of heterologous proteins. PMID- 11778880 TI - Cell surface-engineered yeast displaying a histidine oligopeptide (hexa-His) has enhanced adsorption of and tolerance to heavy metal ions. AB - A histidine oligopeptide (hexa-His) with the ability to chelate divalent heavy metal ions was displayed on the yeast cell surface for the purpose of enhanced adsorption of heavy metal ions. We genetically fused a hexa-His-encoding gene with the gene encoding the C-terminal half of alpha-agglutinin that includes a glycosylphosphatidylinositol anchor attachment signal sequence and attached the hexa-His peptide on the cell wall of Saccharomyces cerevisiae. This surface engineered yeast adsorbed three to eight times more copper ions than the parent strain and was more resistant to copper (4 mM) than the parent (below 1 mM at pH 7.8). It was possible to recover about a half of the copper ions adsorbed by whole cells with EDTA treatment without disintegrating the cells. Thus, we succeeded in constructing a novel yeast cell with both tolerance to toxic contaminants and enhanced adsorption of metal ions onto the cell surface. PMID- 11778881 TI - Intelligent yeast strains with the ability to self-monitor the concentrations of intra- and extracellular phosphate or ammonium ion by emission of fluorescence from the cell surface. AB - Saccharomyces cerevisiae strains that respond to environmental changes and transmit the information by emission of fluorescence from the cell surface were constructed. The technique of cell surface engineering enabled the yeast cells to display enhanced cyan blue fluorescent protein (ECFP) or enhanced yellow fluorescent protein (EYFP) on the surface under the control of promoters that sense environmental changes. Two model promoters were examined in this study. For monitoring the intra- and extracellular concentrations of phosphate ion, the PHO5 promoter was chosen to display ECFP. The MEP2 promoter was used to display EYFP to sense the concentrations of ammonium ion. Fluorescence was observed by fluorescence microscopy and immunofluorescence microscopy, and the intensity was measured by a flow cytometer. The relationship between ion concentration inside and outside the cells was evaluated by the change in the rate of fluorescence. This S. cerevisiae system enables environmental changes to be transmitted as intra- and extracellular information using a suitable promoter functioning at real time and in a non-invasive manner. PMID- 11778882 TI - Growth inhibition of a Fusarium verticillioides GUS strain in corn kernels of aflatoxin-resistant genotypes. AB - Two corn genotypes, GT-MAS:gk and MI82, resistant to Aspergillus flavus infection/aflatoxin contamination, were tested for their ability to limit growth of Fusarium verticillioides. An F. verticillioides strain was transformed with a beta-glucuronidase (GUS) reporter gene (uidA) construct to facilitate fungal growth quantification and then inoculated onto endosperm-wounded and non-wounded kernels of the above-corn lines. To serve as a control, an A. flavus strain containing the same reporter gene construct was inoculated onto non-wounded kernels of GT-MAS:gk. Results showed that, as in a previous study, non-wounded GT MAS:gk kernels supported less growth (six- to ten-fold) of A. flavus than did kernels of a susceptible control. Also, non-wounded kernels of GT-MAS:gk and M182 supported less growth (two- to four-fold) of F. verticillioides than did susceptible kernels. Wounding, however, increased F. verticillioides infection of MI82, but not that of GT-MAS:gk. This is in contrast to a previous study of A. flavus, where wounding increased infection of GT-MAS:gk rather than M182 kernels. Further study is needed to explain genotypic variation in the kernel response to A. flavus and F. verticillioides kernel infections. Also, the potential for aflatoxin-resistant corn lines to likewise inhibit growth of F. verticillioides needs to be confirmed in the field. PMID- 11778883 TI - Assessment of heavy metal bioavailability using Escherichia coli zntAp::lux and copAp::lux-based biosensors. AB - To determine the amount of metals detectable by bacteria, two plasmids were constructed in which the metal-inducible zntA and copA promoters from Escherichia coli were fused to a promoterless Vibrio fischeri luxCDABE operon. The luminescence response of E. coli bearing these constructs was studied as a function of the concentration of several heavy metals and was shown to be influenced by cell growth phase. The zntAp::lux fusion is induced mainly by salts of cadmium, lead, mercury and zinc, with significant induction by other metal ions, whereas the specificity of copA induction is restricted to copper and silver. In optimized assay conditions, metals could be detected at threshold concentrations ranging from nanomolar to micromolar, with maximal induction observed after only 60-100 min incubation. The ability of these biosensor strains to distinguish bioavailable quantities of metals in a sample makes them good candidates as useful tools to monitor metal contamination in environmental samples. PMID- 11778884 TI - Major proteins related to chlortetracycline biosynthesis in a Streptomyces aureofaciens production strain studied by quantitative proteomics. AB - Changes in synthesis and abundance of proteins associated with chlortetracycline (CTC) production in Streptomyces aureofaciens were investigated by two dimensional polyacrylamide gel electrophoresis of proteins pulse-labelled in vivo with L-[35S]methionine. Eleven individual protein spots were selected as being related to formation of the antibiotic. Expression of these prominent proteins was not observed in the non-producing mutant; moreover, they were overexpressed in cultures grown in the presence of benzyl thiocyanate, a specific stimulator of CTC biosynthesis used in industrial fermentations. The expression kinetics of the selected proteins was assessed using the technique of computer-assisted image analysis with the EQIAS software and the elongation factor Tu as an internal standard. Interestingly, the kinetic profiles were generally not identical. including those of anhydrotetracycline monooxygenase and the 13-kDa subunit of tetracycline dehydrogenase, two enzymes involved, in the terminal sequential steps of the CTC biosynthetic pathway. The presence of more forms of these enzymes with different charge characteristics was observed. The data presented demonstrated how dramatically the industrial microorganism can change its protein repertoire during the production phase; at least five proteins were nearly comparable in level to the most prominent proteins, exemplified by elongation factor Tu. PMID- 11778885 TI - Evidence of a new biotransformation pathway of p-coumaric acid into p hydroxybenzaldehyde in Pycnoporus cinnabarinus. AB - Pycnoporus cinnabarinus MUCL39533 was shown to be able to convert p-coumaric acid into p-hydroxybenzaldehyde, a component of high organoleptic note present in natural vanilla aroma. Use of phospholipid-enriched medium led to high-density cultures of P. cinnabarinus, since dry mycelial biomass was increased three-fold as compared to glucose medium. In the presence of phospholipids, 155 mg l(-1) p hydroxybenzaldehyde was produced as the major compound on culture day 13 with a molar yield of 26%. The degradation pathways of p-coumaric acid were investigated. Based on the different metabolites identified, an oxidative side chain degradation pathway of p-coumaric acid conversion to p-hydroxybenzoic acid was suggested. This acid was further reduced to p-hydroxybenzaldehyde and p hydroxybenzyl alcohol, or hydroxylated and reduced to protocatechyl derivatives. Additionally, a reductive pathway of p-coumaric acid with 3-(4-hydroxyphenyl) propanol as the terminal product occurred. PMID- 11778886 TI - Geraniol biotransformation-pathway in spores of Penicillium digitatum. AB - Spores of Penicillium digitatum ATCC 201167 transform geraniol, nerol, citral, and geranic acid into methylheptenone. Spore extracts of P. digitatum convert geraniol and nerol NAD+-dependently into citral. Spore extract also converts citral NAD+-dependently into geranic acid. Furthermore, a novel enzymatic activity, citral lyase, which cofactor-independently converts citral into methylheptenone and acetaldehyde, was detected. These result show that spores of P. digitatum convert geraniol via a novel biotransformation pathway. This is the first time a biotransformation pathway in fungal spores has been substantiated by biochemical studies. Geraniol and nerol are converted into citral by citrol dehydrogenase activity. The citral formed is subsequently deacetylated by citral lyase activity, forming methylheptenone. Moreover, citral is converted reversibly into geranic acid by citral dehydrogenase activity. PMID- 11778888 TI - Determination of the kinetic parameters of the phenol-degrading thermophile Bacillus themoleovorans sp. A2. AB - Phenolic compounds are pollutants in many wastewaters, e.g. from crude oil refineries, coal gasification plants or olive oil mills. Phenol removal is a key process for the biodegradation of pollutants at high temperatures because even low concentrations of phenol can inhibit microorganisms severely. Bacillus thermoleovorans sp. A2, a recently isolated thermophilic strain (temperature optimum 65 degrees C), was investigated for its capacity to degrade phenol. The experiments revealed that growth rates were about four times higher than those of mesophilic microorganisms such as Pseudomonas putida. Very high specific growth rates of 2.8 h(-1) were measured at phenol concentrations of 15 mg/l, while at phenol concentrations of 100-500 mg/l growth rates were still in the range of 1 h(-1). The growth kinetics of the thermophilic Bacillus thermoleovorans sp. A2 on phenol as sole carbon and energy source can be described using a three-parameter model developed in enzyme kinetics. The yield coefficient Yx/s of 0.8-1 g cell dry weight/g phenol was considerably higher than cell yields of mesophilic bacteria (Yx/s 0.40-0.52 g cell dry weight/g phenol). The highest growth rate was found at pH 6. Bacillus thermoleovorans sp. A2 was found to be insensitive to hydrodynamic shear stress in stirred bioreactor experiments (despite possible membrane damage caused by phenol) and flourished at an ionic strength of the medium of 0.25(-1) mol/l (equivalent to about 15-60 g NaCl/l). These exceptional properties make Bacillus thermoleovorans sp. A2 an excellent candidate for technical applications. PMID- 11778887 TI - Metabolic study of the adaptation of the yeast Candida guilliermondii to sugarcane bagasse hydrolysate. AB - Batch xylitol production from concentrated sugarcane bagasse hydrolysate by Candida guilliermondii was performed by progressively adapting the cells to the medium. Samples were analyzed to monitor sugar and acetic acid consumption, xylitol, arabitol, ethanol, and carbon dioxide production, as well as cell growth. Both xylitol yield and volumetric productivity remarkably increased with the number of adaptations, demonstrating that the more adapted the cells, the better the capacity of the yeast to reduce xylose to xylitol in hemicellulose hydrolysates. Substrate and product concentrations were used in carbon material balances to study in which way the different carbon sources were utilized by this yeast under microaerobic conditions, as well as to shed light on the effect of the progressive adaptation to the medium on its fermentative activity. Such a theoretical means allowed estimation for the first time of the relative contribution of each medium component to the formation of the main products of this fermentation system. PMID- 11778889 TI - Evidence for three distinct hydrogenase activities in Rhodospirillum rubrum. AB - Inducer, inhibitor, and mutant studies on three hydrogenase activities of Rhodospirillum rubrum indicate that they are mediated by three distinct hydrogenase enzymes. Uptake hydrogenase mediates H2 uptake to an unknown physiological acceptor or methylene blue and is maximally synthesized during autotrophic growth in light. Formate-linked hydrogenase is synthesized primarily during growth in darkness or when light becomes limiting, and links formate oxidation to H2 production. Carbon-monoxide-linked hydrogenase is induced whenever CO is present and couples CO oxidation to H2 evolution. The enzymes can be expressed singly or conjointly depending on growth conditions, and the inhibitor or inducer added. All three hydrogenases can use methyl viologen as the mediator for both the H2 evolution and H2 uptake reactions while displaying distinct pH optima, reversibility, and sensitivity to C2H2 gas. Yet, we present evidence that the CO-linked hydrogenase, unlike the uptake hydrogenase, does not link to methylene blue as the electron acceptor. These differences allow conditions to be established to quantitatively assay each hydrogenase independently of the others both in vivo and in vitro. PMID- 11778890 TI - Luminescent method for the detection of antibacterial activities. AB - A new rapid and sensitive method for the detection of antibacterial activities was based on luminescent indicator strains. Listeria innocua 8811 and Enterococcus faecalis 32 were transformed with plasmid carrying bacterial luciferase genes. Subsequent strains became capable to emit light during the exponential growth phase. The addition of bacteriocin containing culture supernatants to such cultures induced a drop of their light emission which was correlated to the combined antibacterial activity of acid stress and bacteriocin. The detection of antagonistic activity is independent of its mode of action, i.e. bactericidal or bacteriostatic. This method allowed to directly visualize the antagonistic activity of bacteriocin producer strains toward target strains in coculture experiments. However, a control co-culture with non-producing bacteriocin mutant was necessary in order to distinguish between nutrients competition and bacteriocin activity. Finally, five class IIa bacteriocins were purified from culture supernatants of eight strains detected in 3 days from a 120 lactic acid bacteria collection. PMID- 11778891 TI - Isolation of Bacillus subtilis (chungkookjang), a poly-gamma-glutamate producer with high genetic competence. AB - A bacterium with high poly-gamma-glutamate (PGA) productivity was isolated from the traditional Korean seasoning, Chung-Kook-Jang. This bacterium could be classified as a Bacillus subtilis, but sporulation in culture was infrequent in the absence of Mn2+. It was judged to be a variety of B. subtilis and designated B. subtilis (chungkookjang). L-Glutamate significantly induced PGA production, and highly elongated PGAs were synthesized. The volumetric yield reached 13.5 mg ml(-1) in the presence of 2% L-glutamate. The D-glutamate content was over 50% in every PGA produced under the conditions used. During PGA production, glutamate racemase activity was found in the cells, suggesting that the enzyme is involved in the D-glutamate supply. Molecular sizes of PGAs were changed by the salt concentration in the medium; PGAs with comparatively low molecular masses were produced in culture media containing high concentrations of NaCl. B. subtilis (chungkookjang) harbors no plasmid and is the first B. subtilis strain reported with both naturally high PGA productivity and high genetic competence. PMID- 11778892 TI - Controlled release of water-soluble polymeric complexes of sorbic acid with antifungal activities. AB - We synthesized six water-soluble polymeric complexes of sorbic acid with polyvinylpyrrolidone of different molecular weight (mol wt). As shown by infrared absorption spectrum analysis, the complexes were formed by hydrogen bonding. The complexes (SC1, with mol wt=10 kDa, SC2 with mol wt=25 kDa, SC3 with mol wt=30 kDa, SC4 with mol wt=40 kDa, SC5 with mol wt=90 kDa, and SC6 with mol wt=360 kDa) were characterized as low mol wt (SC1, SC2, and SC3) and high mol wt (SC4, SC5, and SC6). The antifungal potencies of the complexes were tested by the macrodilution susceptibility method against environmental and clinically important fungi. Sorbic acid as well as the complexes exhibited minimum inhibitory concentrations (MICs) lower than potassium sorbate against all the strains tested. MICs of SC1, SC2, and SC3 were shown to be 2- to 4-fold lower for yeast and 1.5- to 3-fold lower than those of sorbic acid for moulds, respectively. The MICs of SC4 and SC5 against both of the Candida species tested ranged from 500 to 800 microg/ml, whereas for SC6 and sorbic acid they were about 1 mg/ml. The potencies of the high mol wt complexes against moulds were decreased by increasing the mol wt. For both of the moulds tested, the MICs of SC4 were slightly lower than those of sorbate. The MICs of sorbic acid and SC5 were equal to 300 microg/ml and 500 microg/ml respectively for Aspergillus parasiticus and for Penicillum viridicatum. The susceptibility to SC6 of all of the hyphomycetes tested was higher than that to sorbic acid. The low mol wt complexes and the sorbic acid exhibited minimal fungicidal concentrations (MFCs) 2 and 3 times higher respectively than the MICs. Sorbic acid and SC3 at a concentration of 2.5 mg/ml in an in vitro time kill curve study of Candida tropicalis were shown to be fungistatic, whereas SC1 and SC2 were fungicidal at the same concentrations. For Aspergillus parasiticus sorbic acid at 2.5 mg/ml was fungistatic for a 24-h period, whereas SC1, SC2, and SC3 were fungicidal. PMID- 11778893 TI - Analysis of the microbial communities on corroded concrete sewer pipes--a case study. AB - Conventional as well as molecular techniques have been used to determine the microbial communities present on the concrete walls of sewer pipes. The genetic fingerprint of the microbiota on corroded concrete sewer pipes was obtained by means of denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene fragments. The DGGE profiles of the bacterial communities present on the concrete surface changed as observed by shifts occurring at the level of the dominance of bands from non-corroded places to the most severely corroded places. By means of statistical tools, it was possible to distinguish two different groups, corresponding to the microbial communities on corroded and non-corroded surfaces, respectively. Characterization of the microbial communities indicated that the sequences of typical bands showed the highest level of identity to sequences from the bacterial strains Thiobacillus thiooxidans, Acidithiobacillus sp., Mycobacterium sp. and different heterotrophs belonging to the alpha-, beta- and gamma-Proteobacteria, Acidobacteria and Actinobacteria. In addition, the presence of N-acyl-homoserine lactone signal molecules was shown by two bio-assays of the biofilm on the concrete under the water level and at the most severely corroded places on the concrete surface of the sewer pipe. PMID- 11778894 TI - Anaerobic reductive dechlorination of chlorinated dioxins in estuarine sediments. AB - The biotransformation of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-tetraCDD) under anaerobic sulfate-reducing, methanogenic, and iron-reducing conditions was examined with anaerobic enrichment cultures established with sediment from an estuarine intertidal strait in the New York/New Jersey harbor. In addition, the effect of prior enrichment on 2-bromophenol or a mixture of 2-, 3-, and 4 bromophenol on dioxin dechlorination was examined. All enrichments were spiked with 1 ppm 1,2,3,4-tetraCDD and monitored by gas chromatography-mass spectrometry for up to a 3-year period. Reductive dechlorination was initially observed only under methanogenic conditions in the cultures enriched on all three bromophenol isomers. 1,2,3,4-TetraCDD was dechlorinated in the lateral position to 1,2,4 triCDD. The initial appearance of 1,2,4-triCDD was observed after 2 months, with further dechlorination to 1,3-diCDD within 17 months. PMID- 11778895 TI - Ammonia removal from prawn aquaculture water using immobilized nitrifying bacteria. AB - Intensive prawn aquaculture in tropical regions is associated with high concentrations of total ammoniacal nitrogen (TAN) as a result of high rates of prawn excretion and feed loading. Excessive TAN can adversely effect productivity and result in adverse impacts on coastal waters. Cultures of indigenous nitrifying bacteria were enriched from intensive prawn aquaculture pond water using continuous and batch enrichment techniques. Cultures were capable of TAN removal over a wide range of initial TAN concentrations - up to 200 mg/l. Cultures were immobilized onto porous clay pellets to enhance cell density and applied to culture medium and TAN-augmented pond water under aerobic conditions to determine TAN removal proficiency. Immobilized cultures were able to achieve a high TAN removal proficiency in pond water--even at a low density of 0.1 pellet per liter. A concentration of less than 0.5 mg TAN/l could be maintained under a fed-batch condition of 3.2 mg TAN/l per day, after an initial 2-day lag phase. A simplified and effective culture enrichment process was developed for culture immobilization onto pellets using TAN-augmented pond water. Overall, pellet immobilization of indigenous nitrifying bacteria represents a potentially effective TAN control system for prawn aquaculture in low-cost, but intensive tropical prawn farms. PMID- 11778896 TI - Assay for determination of alpha-glucosidase and peptidase activity and location in a nitrifying trickling filter. AB - Enzymatic alpha-glucosidase and peptidase activity in a nitrifying trickling filter (NTF) at the Rya wastewater treatment plant, Goteborg, Sweden, was investigated to evaluate whether these activities can be used as indicators of heterotrophic activity and polymer degradation. Samples of the biofilm were taken from the NTF and incubated in sterile filtered effluent water from the NTF with the addition of soluble starch, peptone, and ammonium chloride. In order to determine the distribution of enzyme activities, the alpha-glucosidase and peptidase activities were measured in the biofilm samples, in the filtered effluent water from the NTF and in the water phase in which the biofilm was incubated. Activities of both enzymes were found both in the effluent water from the NTF and in the biofilm. The enzyme activities were elevated in the samples when starch and peptone were present. In addition, there was a significant inhibition of ammonium oxidation in samples incubated with starch and peptone. Thus, the presence of starch, peptone and ammonium resulted in increased activity of heterotrophs, which lead to an inhibition of the nitrifiers, probably via competition for available oxygen. PMID- 11778897 TI - Basic examinations on chemical pre-oxidation by ozone for enhancing bioremediation of phenanthrene contaminated soils. AB - Biological treatment of polycyclic aromatic hydrocarbons (PAH) has been demonstrated to be a feasible and common remediation technology which has been successfully applied to the clean-up of contaminated soils. Because bioavailability of the contaminants is of great importance for a successful bioremediation, a chemical pre-oxidation step by ozone was tested to enhance the subsequent biodegradation steps. Oxidation of PAH by ozone should result in reaction products that have a better solubility in water and thus a better bioavailability. A major part of this work was done by examinations of the model substance phenanthrene as a typical compound of PAH. After initial ozonation of phenanthrene, analysis by GC-MS showed at least seven identified conversion products of phenanthrene. In comparison with phenanthrene these conversion products were more efficiently biodegraded by Sphingomonas yanoikuyae or mixed cultures when the ozonation process resulted in monoaromatic compounds. Primary ozonation products with biphenylic structures were found not to be biodegradable. Investigations into the toxicity of contaminated and ozonated soils were carried out by well-established toxicity assays using Bacillus subtilis and garden cress. The ozonated soils surprisingly showed higher toxic or inhibitory effects towards different organisms than the phenanthrene or PAH itself. The microbial degradation of phenanthrene in slurry reactors by S. yanoikuyae was not enhanced significantly by preozonation of the contaminated soil. PMID- 11778898 TI - Studies on the decolourisation of an artificial textile-effluent by white-rot fungi in N-rich and N-limited media. AB - Coriolopsis gallica and Phanerochaete chrysosporium were selected for their potential ability to degrade five dyes in an artificial effluent. Degradation experiments were carried out in N-rich (C:N ratio 11.6:1) and N-limited (116:1) conditions at an effluent concentration of 100 mg l(-1). P. chrysosporium decolourised 53.6% of the effluent in N-rich conditions and 48% in N-limited conditions. C. gallica decolourised 80.7% in N-rich conditions and 86.9% in N limited conditions. Nitrogen supplementation improved enzyme activities and dye decolourisation for P. chrysosporium. Additional nitrogen increased enzyme activities for C. gallica but did not improve decolourisation. The results highlight the potential of C. gallica for textile dye degradation. PMID- 11778899 TI - Intracellular trafficking of retroviral genomes during the early phase of infection: viral exploitation of cellular pathways. AB - Retroviruses enter cells through specific cell-surface receptors and then embark on a journey that ultimately leads to the establishment of the integrated proviral DNA. The steps of the journey include the reverse transcription of the viral RNA into DNA, the trafficking of the viral protein-DNA complex through the cytoplasm, the entry of the complex into the nucleus, and the insertion of the linear viral DNA into the host genome. All these steps are likely to involve specific interactions of viral proteins with host machinery. Our knowledge of the details of these interactions is very limited but is rapidly expanding, and should provide a deeper understanding of the pathways and components used by the different classes of retroviruses. This knowledge in turn should enable the development of better and more efficient retroviral vectors for use in gene therapy protocols in vivo. PMID- 11778900 TI - Dual-regulated expression technology: a new era in the adjustment of heterologous gene expression in mammalian cells. AB - BACKGROUND: On the basis of the compatible streptogramin- and tetracycline responsive expression systems, a series of dual-regulated expression systems have been established for use in sophisticated biopharmaceutical manufacturing, advanced gene therapy, and tissue engineering. METHODS: Dual-regulated expression concepts enable streptogramin- and tetracycline-responsive control of two different (sets of) transgenes (multi-regulated multigene metabolic engineering), dual-autoregulated expression configurations for one-step chromosomal integration of two antibiotic-adjustable expression units, and artificial regulatory cascades for multi-level regulation of transgenes and optimized integration of molecular interventions into mammalian regulatory networks. RESULTS: This report describes the construction and testing of a family of dual-regulated expression vectors which are compatible with the pTRIDENT vector construction kit, and, in some cases, adapted for retroviral expression technology enabling straightforward transduction of difficult-to-transfect cell lines such as primary cells and stem cells. CONCLUSIONS: Dual-regulated expression technology will probably become of prime interest for a variety of therapeutic applications, including biopharmaceutical manufacturing, gene therapy, and tissue engineering. PMID- 11778901 TI - Adenovirus type 5 uptake by lung adenocarcinoma cells in culture correlates with Ad5 fibre binding is mediated by alpha(v)beta1 integrin and can be modulated by changes in beta1 integrin function. AB - BACKGROUND: Recombinant adenoviruses (Ad) have been employed as vectors for a wide variety of gene therapy applications, but their use has been hindered by problems relating to efficacy and safety. The efficiency of Ad-mediated gene transfer depends on the interaction of the fibre and penton base proteins with their corresponding cell receptors. Ad infection is initiated by the formation of a high affinity complex between the fibre protein and a host cell protein that for most Ad serotypes is CAR (the coxsackie B virus and Ad receptor). A second molecule, the MHC class I, may also be involved in Ad type 2 and Ad type 5 uptake. Ad internalization results from the interaction of the penton base protein with cell surface integrins alpha(v)beta3 and alpha(v)beta5. In this study, we addressed the interaction between Ad type 5 (Ad5) and its receptors on lung derived adenocarcinoma cells in culture. METHODS: Using flow cytometry, we determined the level of expression of attachment and internalization receptors that are expressed on the cell surface of A549, H322 and H441 lung-derived adenocarcinoma cells in culture. The level of alpha(v)beta1 cell surface integrin was assessed by immunoprecipitation. Measuring the level of luciferase gene expression at different viral titres quantitated Ad5 uptake by these cells. The kinetics of binding of Ad5 fibre knobs to A549, H322 and H441 cells was assessed in direct binding studies using 125I labelling of purified recombinant Ad5 fibre knob domains. In order to assess the functionality of integrins, adhesion assays were performed in the presence or absence of activators of integrin function. In competition experiments, prior to exposure to the virus, the cells were pre incubated with purified recombinant Ad5 fibre-knob domains, function blocking anti-integrin antibodies, or integrin activating agents, prior to the introduction of luciferase expressing Ad5. RESULTS: We found that Ad5-mediated gene transfer in A549, H322 and H441 adenocarcinoma cells in culture is highly variable and that this variation correlates with specific binding of Ad5 fibre knob domain binding to the cell surface. We also found, for the first time, that Ad5 infection is mediated by integrin alpha(v)beta1 and that functional activation of beta1 integrin by means of the specific anti-beta1 monoclonal antibody, TS2/16, induced increased A549 cell adhesion to fibronectin and vitronectin and also enhanced Ad5 uptake by these cells. CONCLUSIONS: Our studies demonstrate that the Ad5 fibre-knob domain interaction with CAR represents a major determinant of Ad5-mediated gene transfer to lung-derived adenocarcinoma cells in culture. The finding that integrin alpha(v)beta1 is involved in Ad5 infection has implications for the use of recombinant Ad5 vectors for cancer gene therapy, since alpha(v)beta1 is expressed at high levels and acts as an alternative vitronectin receptor in many epithelial and some melanoma tumours which express no alpha(v)beta3 and constant low levels of alpha(v)beta5. The fact that the beta1 integrin-activating antibody TS2/16 can enhance alpha(v)beta1 mediated Ad5 infection suggests that the efficacy of Ad5-mediated gene transfer might be influenced not only by the level of cell surface expression of integrins but also by their state of activation. PMID- 11778902 TI - A powerful cooperative interaction between a fusogenic peptide and lipofectamine for the enhancement of receptor-targeted, non-viral gene delivery via integrin receptors. AB - BACKGROUND: Following receptor-mediated endocytosis, vector/DNA complexes require assistance to exit endocytic vesicles in order to avoid degradation in the lysosomes. Overcoming this barrier is a major challenge for the development of receptor-targeted, non-viral gene delivery. METHODS: The fusogenic peptide of influenza virus haemagglutinin, lipofectamine and chloroquine were tested singly and in combination in various doses for promoting in vitro gene transfer by an integrin-targeted, non-viral DNA vector (polylysine-molossin). RESULTS: The fusogenic peptide and lipofectamine both individually promoted integrin-targeted gene delivery. However, the combined use of these agents was particularly effective, even at concentrations where neither agent singly had any effect on promoting gene delivery by polylysine-molossin. This optimal combination was effective on several cell lines and primary cell cultures. On the HuH7 cell line, it was approximately five-fold more effective than optimal chloroquine concentrations for integrin-targeted gene delivery and four to five times more effective than commercially available polyethylenimine. With the beta galactosidase reporter gene, 60-65% of HepG2 cells and 75-80% of HuH7 cells were positive. The surface charge of polylysine-molossin/DNA/lipofectamine/fusogenic peptide complexes was approximately the same as that of polylysine-molossin/DNA complexes. The size distribution of the complexes suggested that competitive binding of polylysine-molossin and lipofectamine to DNA influenced the overall efficacy of this approach. CONCLUSIONS: Although the mechanisms are not clear, the combined use of very low doses of two membrane-destabilizing agents results in high levels of receptor-targeted gene delivery. PMID- 11778903 TI - Improving plasmid DNA-mediated liver gene transfer by prolonging its retention in the hepatic vasculature. AB - BACKGROUND: Naked DNA is the simplest and safest method to deliver genes to the liver. In this study, we demonstrate that significant gene expression could be achieved in the liver by transiently restricting blood flow through the liver immediately following peripheral intravenous injection of plasmid DNA. METHODS: Mice were intravenously (tail vein) injected with plasmid DNA in 100 microl of saline (0.9% NaCl) immediately followed by 8 s of occlusion of blood flow through the liver. The occlusion of blood flow was performed by using a clip at either the vena cava (VC) or at the portal vein and hepatic artery (PV+HA). Alternatively, the VC was clamped for 4 s followed by clamping the PV+HA for 4 s (VC and PV+HA). RESULTS: Gene transfer to the liver was completed after blood flow through the liver was blocked for as short as 1 s. Up to 560 pg of luciferase protein per mg of extracted protein was observed from the liver after a single injection of 80 microg of plasmid DNA. Gene expression was increased more than 50-fold by the combination of clamping and electroporation. CONCLUSION: This is the first demonstration of gene transfer to the liver via systemic administration without using any carrier system or physical force. Also, the technique provides new insights into the mechanism of hepatic gene transfer. PMID- 11778904 TI - Production, purification and analysis of an experimental DNA vaccine against rabies. AB - BACKGROUND: The basic and applied research efforts devoted to the development of DNA vaccines must be accompanied by manufacturing processes capable of being scaled up and delivering a clinical-grade product. This work describes a rapid process of this kind, based on hydrophobic interaction chromatography (HIC) for the production of milligram quantities of an experimental DNA rabies vaccine. Its properties and protective activity are tested in comparison with the same plasmid DNA purified with a commercial kit. METHODS: The experimental DNA vaccine encoding the rabies virus glycoprotein was amplified in vivo in Escherichia coli. The plasmid was isolated by alkaline lysis, pre-purified and concentrated by isopropanol and (NH4)2SO4 precipitation, and purified by HIC and dialysis. Product quality was controlled by using high-performance liquid chromatography (HPLC), Southern slot blotting, agarose gel electrophoresis, the kinetic-QCL Limulus amoebocyte lysate assay, and protein assays. The expression of the rabies virus glycoprotein was tested in vitro in neuroblastoma cells. The production of rabies-virus-neutralising antibodies and the protection against an intracerebral virus challenge were tested in mice. RESULTS: One hundred and forty-two milligrams of the plasmid, with an HPLC purity greater than 99% were obtained from 4.5 l medium. Control analysis showed that the vaccine conforms to specifications in terms of impurities (endotoxins, genomic DNA, RNA, proteins). Furthermore, the final experimental vaccine induces rabies-virus-neutralising antibodies and protects mice against a rabies virus challenge. CONCLUSIONS: This study demonstrates that the method developed for the purification of milligram amounts of plasmid delivers an endotoxin-free, experimental rabies DNA vaccine, with protective activity similar to that obtained with the vaccine purified using a commercial kit. PMID- 11778905 TI - Cell-based delivery of cytokines allows for the differentiation of a doxycycline inducible oligodendrocyte precursor cell line in vitro. AB - BACKGROUND: Stem cells, having the property of self renewal, offer the promise of lifelong repair of damaged tissue. However, somatic tissue-committed primary stem cells are rare and difficult to expand in vitro. Genetically modified stem-like cells with the ability to expand conditionally provide a valuable tool with which to study stem cell biology, especially the cellular events of proliferation and differentiation. In addition, stem cells may be appropriate candidates for therapeutic applications. METHODS: Double transgenic mice possesing SV40 T antigen (Tag) under the control of the reverse tetracycline-transactivator (rtTA) were used to establish cell lines. One brain cell line was partially characterized by DNA sequencing, morphology, antigen expression using flow cytometry, confocal microscopy, and electrophysiology using the patch clamp technique. Cell cycle analysis was performed using propidium iodide staining; cell viability and H3-thymidine incorporation assays. The ability of this cell line to differentiate was assessed by confocal microscopy following co-culture with stem cells secreting cytokines. RESULTS: We report here the establishment and partial characterization of a cell line derived from the brain tissue of rtTA SV40 Tag transgenic mice. Analysis of the morphology and antigen markers has shown that this cell line mimics some aspects of primary glial precursors. The results of electrophysiology are consistent with this and suggest that the cell line is derived from O2A glial precursor cells. Cell cycle progression of this cell line is doxycycline-dependent. In the absence of doxycycline, cells become apoptotic. Differentiation into mature type 2 astrocytes and (precursor) oligodendrocytes can be induced upon withdrawal of doxycycline and addition of epithelial stem cells secreting cytokine, such as hIL3 (human Interleukine 3) or hIL6 to the culture. In contrast, co-culturing with hCNTF (human Ciliary NeuroTrophic Factor)-secreting epithelial stem cells did not induce them to mature into progeny cell types. CONCLUSION: The differentiation of this O2A glial precursor line does not occur automatically in culture. Additional external help is required from the cell-based delivery of appropriate transgenic cytokines. Withdrawal of doxycycline from the culture medium removes the proliferation signals and induces a fatal outcome. PMID- 11778906 TI - The Journal of Gene Medicine 2001 Young Investigator Award. PMID- 11778907 TI - The development of circadian rhythms in the fetus and neonate. AB - The circadian time-keeping system is the neural system that allows predictive adaptation of individuals to the reproducible 24-hour day/night alternations of our planet. A biological clock, the suprachiasmatic nucleus, receives environmental information and imposes a circadian pattern to physiological functions. Since the suprachiasmatic nucleus develops early in gestation and circadian rhythms are present in the fetus and newborn, the circadian system seems to be functional in fetal life and can receive circadian inputs through the mother. The neonate moves to an environment in which the main time giving signal is the light:dark cycle. Teleologically, a term newborn should be fit to face this challenge. But this may be quite different for a preterm infant that trades the circadian environment to which it was previously exposed for the timeless environment of the Neonatal Intensive Care Nursery. Scientists and physicians should seek new experimental and clinical approaches to answer the challenging questions of perinatal chronomedicine. PMID- 11778908 TI - The hypothalamic pituitary axis in the fetus and newborn. AB - Glucocorticoid receptor activation in the fetal lung triggers maturation necessary for extra-uterine life. Antenatal treatment with betamethasone and dexamethasone has lowered severity of respiratory distress in very low birth weight infants, and dexamethasone given postnatally has resulted in short-term improvement in chronic lung disease. Recently, however, surfactant therapy has diminished the differential benefit of antenatal glucocorticoid treatment, and it has been difficult to show that postnatal dexamethasone therapy improves survival. Treated infants may have reduced weight gain, adrenal suppression, increased incidence of intestinal perforation and infection, and long-term developmental and metabolic problems. Recent data suggest that the fetal hypothalamic/pituitary/adrenal axis is active early and is precisely structured for an intricate sequence of specifically fetal developmental events, which may be deranged by dexamethasone therapy. We consider data suggesting that persistence of the fetal pattern in some premature infants constitutes adrenal insufficiency, and that therapy at stress replacement doses with less potent glucocorticoids might avoid side effects seen with traditional regimens. PMID- 11778909 TI - Controversies in the use of antenatal steroids for fetal maturation. AB - After decades of caution and reticence, by the early 1990s, the use of antenatal corticosteroids was accepted as a pharmacologic intervention to reduce neonatal morbidity and mortality associated with prematurity. Many prospective studies yielded robust evidence to support the use of corticosteroids for fetal maturation. Their use is no longer disputed. Nevertheless, many unanswered questions remain regarding issues such as the ideal dose, drug form, regimen, or timing of treatment. This article explores many of the unanswered questions associated with antenatal corticosteroid use. PMID- 11778910 TI - Controversies in the use of postnatal steroids. AB - This review evaluates and compares, by using the best available medical evidence, the risks and benefits of postnatal steroid use in very low birth weight infants. Systemic postnatal steroids are effective at reducing the risk of chronic lung disease in ventilated very low birth weight infants; they appear to be most effective when administered to ventilator-dependent infants at 7 to 14 days of age. The beneficial effects are accompanied by an increase in the risk of long term neurologic sequelae in addition to a number of short-term complications. Whether these risks are justified is largely dependent on the relative value that a parent or caregiver would place on chronic lung disease as compared to the adverse neurologic sequelae. PMID- 11778912 TI - Postnatal thyroid hormone replacement in very preterm infants. AB - Transient hypothyroxinemia occurs frequently in very preterm infants and is caused by a combination of factors as immaturity of the hypothalamo-pituitary thyroid system, loss of the maternal thyroxine (T4) contribution, immaturity of thyroid hormone metabolism, and neonatal illness. Thyroid hormone is important in maturation of the brain, but also of heart and lungs. Low neonatal T4 concentrations in plasma are related to worse clinical and neurodevelopmental outcome. Despite these relationships, only few randomized clinical trials have been performed to find out whether T4 supplementation can improve clinical and/or neurodevelomental outcome of preterm infants. The currently available evidence does not support use of supplemental T4 in all preterm infants. There are, however, indications that T4 might improve neurodevelopmental outcome in infants born before 27 to 29 weeks of gestation. Therefore, it is necessary that new trials are set up to further study the benefits of thyroid hormones given in the neonatal period of very preterm infants. PMID- 11778911 TI - Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease? AB - Unfortunately, surfactant therapy is not routinely available to infants in some parts of the world because of its cost. It is the hypothesis of this article that in situations where surfactant is not available, there may be a role for antenatal thyrotropin-releasing hormone (TRH) plus glucocorticoid therapy. Data from randomized clinical trials, which compared therapy with antenatal glucocorticoid plus TRH to that with glucocorticoid alone were extracted and subjected to meta-analysis. The trials that incorporated surfactant therapy were analyzed separately from those in which surfactant was not used. In addition, because surfactant therapy was only available to some patients in the Australian ACTOBAT trial, each group analysis was performed with and without the ACTOBAT data. A characteristic of the earlier presurfactant trials is that few were designed for "intention to treat" analysis. In most of these studies, it was decided a priori to include babies who delivered within a specified time period after hormone therapy. The addition of TRH did not decrease respiratory distress syndrome in those trials in which surfactant therapy was used. In the presurfactant trials, respiratory distress syndrome was significantly decreased when "intention to treat" data were examined, as well as in those infants who delivered between 1 and 10 days after maternal therapy. There was also a significant decrease in oxygen dependency at 28 days after birth, and in oxygen dependency or death at this time, in those infants who delivered 1 to 10 days after treatment. Antenatal TRH had no significant effect of on neonatal complications such as air leak, intraventricular hemmorhage, patent ductus arteriosus, retinopathy of prematurity, or necrotizing enterocolitis. However, TRH did produce transient suppression of the pituitary thyroid axis. There were also a variety of transient complications in the mothers, including nausea, vomiting or flushing, light-headed feeling, and increased blood pressure. The authors conclude that the implementation of appropriate antenatal glucocorticoid treatment is the first priority. Once this has been established, the data presented here suggest that addition of antenatal TRH should be considered in those situations where surfactant is not available. PMID- 11778913 TI - Insulin and insulin-like growth factors in human development: implications for the perinatal period. AB - The physiologic and cellular mechanisms regulating fetal growth cannot be adequately described by regulatory mechanisms important postnatally. This review summarizes recent advances in clinical medicine, cell and molecular biology, and physiology showing the central and essential roles of insulin and the insulin like growth factor family of peptides in regulating fetal growth. Moreover, the importance of insulin-like growth factors in tissue-specific growth regulation during critical periods of development suggest that these mechanisms may also be relevant to the pathogenesis of tissue injury in the preterm infant, and may offer therapeutic strategies aimed at reducing morbidity associated with prematurity. Illustrations of how the insulin-like growth factor axis may represent potential therapeutic targets for specific clinical problems facing the newborn are briefly discussed. PMID- 11778914 TI - Insulin homeostasis in the extremely low birth weight infant. AB - The need to improve the nutritional status of extremely low birth weight infants has resulted in a higher incidence of problems related to glucose intolerance. The inability of the newborn to inhibit gluconeogenesis in response to a glucose infusion has been postulated as an important determinant of the hyperglycemia observed in extremely low birth weight infants. The 2 proposed mechanisms to explain this finding include inappropriate secretion of insulin by the pancreas and decrease sensitivity of the liver to the gluco-regulatory effect of insulin. The capacity of extremely low birth weight infants to oxidize glucose at higher rates, and the positive effect that insulin may have in glucose utilization and tolerance, support the use of insulin in the prevention and treatment of hyperglycemia. Continuous infusion of insulin appears to be safe for the treatment of hyperglycemia, based on the available studies. However, the effectiveness of insulin treatment needs to be critically tested further before it can be implemented in routine clinical practice. PMID- 11778915 TI - New trends in apheresis. PMID- 11778916 TI - A new endotoxin adsorber: first clinical application. AB - In an open, uncontrolled pilot study, 5 men and 1 woman with suspected gram negative sepsis were treated with a new whole-blood endotoxin adsorption system. Lipopolysaccharide (LPS) adsorption was carried out by hemoperfusion over high affinity polymethacrylate-bound albumin (Fresenius Endotoxin Adsorber EN 500). All patients suffered from endotoxemia (>20 pg/ml LAL) and met at least two systemic inflammatory response syndrome (SIRS) criteria. Four patients suffered from pneumonia due to mechanical ventilation, one from peritonitis, and one from pneumonia and peritonitis. Endotoxin adsorption was very well tolerated, and efficient LPS removal was shown in all patients. Apache II score immediately before immunoadsorption was 23.5 and was 22.3 after the last treatment. All 6 critically ill patients improved substantially and were discharged from the intensive care unit. LPS whole blood immunoadsorption is a promising new method. No side effects have been observed thus far. A large controlled study to prove clinical efficacy in patients with severe sepsis is under way. PMID- 11778917 TI - Fibrinogen adsorption in the diabetic foot syndrome and peripheral arterial occlusive disease: first clinical experience. AB - The elimination of fibrinogen from plasma improves plasma viscosity and whole blood viscosity. For extracorporeal adsorption of fibrinogen, the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B3. Adsorbers containing 135 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 7 men and 3 women (48-75 years old). Nine patients suffered from diabetes mellitus, 1 patient from peripheral arterial occlusive disease, and 5 patients were on regular hemodialysis. Treatments were scheduled on Days 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25, and 28. One hundred forty-four treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen adsorption procedure were observed. In these 10 patients, fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session, fibrinogen concentration was lowered to 241.4 +/- 125.8 mg/dl by treating 4,270 +/- 1,180 ml of plasma. In the following 134 treatments, the pretreatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, and the posttreatment concentration was 120.6 +/- 37.2 mg/dl. The mean amount of plasma treated was 3,737 +/- 1,643 ml, and the mean duration of a treatment session (except first treatment) was 143.7 +/- 63.1 min. In 7 patients, a mean posttreatment fibrinogen concentration of < or = 123 mg/dl was obtained; in the other patients, concentrations of 133, 177, and 184 mg/dl were obtained. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: 82%, -67%, and -73%, respectively. During the treatment period of 28 days, wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective, and safe procedure to lower fibrinogen concentration in plasma. It could be a therapeutic option in severe blood vessel disease in which drug therapy is not sufficient and invasive procedures such as bypass or angioplasty cannot be applied. Yet, more information is needed, for example, about the fibrinogen concentration that has to be reached to get the maximal improvement of micro- and/or macrocirculation. PMID- 11778918 TI - Immunoadsorption in myasthenia gravis based on specific ligands mimicking the immunogenic sites of the acetylcholine receptor. AB - A specific system for antibody removal from blood circulation in myasthenia gravis (MG) patients was devised by use of the immunoadsorbent bound to an acetylcholine receptor (AChR) peptide that was synthesized corresponding to the sequence of residues 183-200 of the AChR alpha-subunit (alpha 183-200), antibodies which prevent the binding of ACh to AChR. The alpha 183-200 peptide was confirmed to be immunogenic for induction of an animal model of the disease and for reactivity with MG autoantibodies. We then made use of these results for immunoadsorption therapy through the antigen-antibody reaction on the molecular level, having given patients relief from myasthenic weakness. The greatest care was taken for the selection of an antigenic region in the molecular structure among various myasthenogenic domains of AChR and for the antigenic conformation of synthetic peptide as the adsorbent to react with antibodies raised against the native protein. PMID- 11778919 TI - Therapeutic plasma exchange in the intensive care setting. AB - The potential to treat life-threatening conditions with therapeutic plasma exchange (TPE) is limited to a few situations. In severe pulmonary hemorrhage as a complication of several immune disorders (e.g., antiglomerular basement membrane antibody disease, Wegener's granulomatosus, lupus erythematosus), TPE should only be considered after conventional measures (mostly pulses of methylprednisolone) have been applied. Idiopathic familial and nonfamilial thrombotic thrombocytopenic purpura as well as the subset of the hemolytic uremic syndrome not associated with diarrhea are clear indications for TPE using fresh frozen plasma as replacement fluid. Patients with myasthenic crisis will also benefit from TPE and will improve within 1 day. Acute pancreatitis as a complication of the chylomicronemia syndrome has a poor prognosis and should be treated with TPE without any delay. In the case of drug overdose or intoxication, the efficiency of TPE to remove the offending drug is usually overestimated. In this situation, TPE is useful only when the plasma protein binding of the substance is high (>80%) and the volume of distribution is low (<0.2 L/kg body weight). TPE is not without risks and hazards (e.g., vascular access, bleeding, allergy), which should also be considered when discussing this extracorporeal therapy in otherwise refractory clinical conditions. PMID- 11778920 TI - High-efficiency DALI apheresis using 1,250 ml adsorbers in a hypercholesterolemic obese patient: a case report. AB - Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins from whole blood and is therefore an easy and rapid procedure. The majority of patients reaches >60% acute low-density lipoprotein cholesterol (LDL-C) reduction using either the DALI 750 or 1000 configuration. However, in patients with extremely high LDL-C levels or very large blood volumes, these configurations may lead to suboptimal results. The current study was performed to test the safety and efficacy of DALI 1250. In a severely obese patient (185 cm, 133 kg, blood volume 7.2 L, LDL-C 239 mg/dl), 11 L of blood (1.53-fold patient blood volume) was processed at a flow rate of 80 ml/min in 2.5 h; a combined heparin-plus-citrate anticoagulation regimen was used. Commercially available DALI 1250 and DALI hardware and disposables were manufactured by Fresenius HemoCare Adsorber Technology, St. Wendel, Germany. Twenty weekly sessions were performed. Clinically and technically, the apheresis sessions were completely uneventful. As compared to DALI 1000 (n = 4 sessions), the reduction rates by DALI 1250 (n = 20) improved for LDL-C (from 52% to 66%), lipoprotein (a) (Lp[a]) (53% vs. 66%), and fibrinogen (11% vs. 16%). There was a slight increase in high-density lipoprotein cholesterol (HDL-C) loss (20% vs. 24%). Moreover, the absolute amount of LDL-C removed per session increased from 5.06 g to 5.94 g. Laboratory safety parameters remained within the normal range, the anticoagulation was well controlled, and the pressure gradients over the adsorber remained constant. In this case report, DALI 1250 was perfectly safe and significantly increased the efficacy of LDL-C and Lp(a) elimination compared to standard DALI. Thus, this high-efficiency version of DALI may be used in patients with extremely high LDL-C levels and/or large blood volumes. PMID- 11778921 TI - DALI low-density lipoprotein apheresis in homozygous and heterozygous familial hypercholesterolemic patients using low-dose citrate anticoagulation. AB - The purpose of this study was to clarify the efficacy and safety of direct adsorption of lipoprotein low-density lipoprotein apheresis (DALI LDL apheresis) in patients with severe homozygous and heterozygous familial hypercholesterolemia who showed minor adverse effects during treatment with the usual DALI configuration (AC 1:20) through the use of a new system with low-dose citrate anticoagulation (AC 1:40) developed in order to minimize citrate-related adverse effects. Serum total cholesterol and LDL-cholesterol (LDL-C) showed a decrease of 57% to 61%, and 62% to 67%, respectively, in the 2 patients. Serum lipoprotein (a) (Lp[a]) was higher in the homozygous patient (Patient 1: MD) and within the normal range in the heterozygous patient (Patient 2: ES). In the former, Lp(a) was reduced by 52%. Serum high-density lipoprotein cholesterol (HDL-C) showed a statistically insignificant acute reduction: 15% to 19%. The observed reduction is mainly related to the well-known effect of hemodilution. The cardiovascular risk (total cholesterol/HDL-C) was reduced in both patients (46% to 54%) as expected. Serum triglycerides were reduced by 33% to 49%. The mean blood volume processed per session was 7,600 ml. Fifteen treatments for each patient have successfully been completed without the appearance of any clinically significant subjective and objective symptoms related to treatment with the new system. PMID- 11778922 TI - Improvement of hemorheology by DALI apheresis: acute effects on plasma viscosity and erythrocyte aggregation in hypercholesterolemic patients. AB - Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 +/- 0.04 to 1.06 +/- 0.3 mPa (-10%) while EA improved from 22.8 +/- 4.4 to 13.3 +/- 4.5 (arbitrary units) (-42%). LDL-cholesterol, Lp(a), and very-low density lipoprotein (VLDL)-cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet. PMID- 11778923 TI - Heparin-Induced extracorporeal low-density lipoprotein precipitation apheresis: a new therapeutic concept in the treatment of sudden hearing loss. AB - Vascular events, immunological processes, and viral infections have to be considered as pathomechanisms for most cases of sudden hearing loss (SHL). In order to clarify predisposing conditions for vascular events. hemorheological parameters have been studied in 53 patients suffering from SHL within 5 days of onset, along with a control group. The striking result was a significantly elevated level of plasma fibrinogen leading to a significantly increased erythrocyte aggregation and plasma viscosity. No significant difference could be found in all other parameters of clinical chemistry, hematology, and hemostasis. These results encouraged us to use heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) apheresis, which acutely and drastically reduces LDL. fibrinogen, and lipoprotein (a) in the treatment of patients suffering from sudden hearing loss and hyperfibrinogenemia or hypercholesterolemia. In a pilot study including 30 patients, we found a better recovery of hearing in the patients treated with a single HELP apheresis when compared to conventional treatment for 10 days with prednisolone and dextranes. Currently, we verify these results in a larger multicenter trial in patients regardless of their fibrinogen or LDL levels. In the future, there will be different specific treatments of sudden hearing loss based on the different pathomechanisms. The clinical impression and first controlled data make it likely that HELP apheresis is useful in the therapy of sudden hearing loss with suspected vascular origin. PMID- 11778924 TI - Effect of heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) apheresis on hepatitis C plasma virus load. AB - Association of the hepatitis C virus (HCV) with apolipoprotein B containing lipoproteins has been suggested, and this led to the concept that the low-density lipoprotein (LDL) receptor may also serve as a candidate receptor for HCV uptake into the liver. We have investigated whether heparin-induced extracorporeal LDL precipitation (HELP) LDL apheresis treatment reduces HCV plasma load in 6 patients, all infected for more than 4 years with HCV and resistant against established anti-HCV therapy. HELP apheresis treatment caused an HCV-RNA decrease of 77.3% in mean. This decline was not correlated with LDL-cholesterol reduction. HCV-RNA was retained on the HELP filter as shown for 1 patient. The effect of RNA lowering was only transient due to the high turnover of HCV. However, HELP apheresis may open a window of opportunity for an immune-modulating and antiviral therapy in the interval between two apheresis procedures in patients with high virus load. PMID- 11778926 TI - Background and indications for protein A-based extracorporeal immunoadsorption. AB - Protein A (SPA), a major cell wall component of Staphylococcus aureus, has occupied numerous investigators from its discovery in the late fifties. Its availability and avid binding to human immunoglobulins have led to extensive usage for diagnostic and research purposes. Today, SPA-based extracorporeal immunoadsorption relies on two rather different systems, namely, SPA-silica (Prosorba), and SPA-Sepharose (Immunosorba). Both systems are approved by the Food and Drug Administration for the core indications of rheumatoid arthritis and idiopathic thrombocytopenic purpura (SPA-silica) or hemophilia with inhibitors (SPA-Sepharose). Off label indications include immune disorders with a conceivable connection between autoantibody titers and disease activity, like forms of glomerulonephritis, systemic lupus erythematodes, myasthenia, and the Guillain-Barre syndrome as well as alloantibody formation in the context of e.g., transplantation. This review summarizes historical developments and important properties of SPA. Indications for extracorporeal therapy are discussed on the basis of available information and personal experience. PMID- 11778925 TI - Heparin-Induced extracorporeal low-density lipoprotein precipitation futura, a new modification of HELP apheresis: technique and first clinical results. AB - Heparin extracorporeal low-density lipoprotein precipitation (HELP) Futura is a new development in the standard HELP Secura system that has been in clinical practice for more than 15 years. Based on this experience, a HELP Upgrading system was first evaluated in a clinical trial to confirm the same clinical results as in the standard system. The upgraded procedure worked with industrially prepared sterile dialysis solutions instead of the reverse osmosis device. The conclusion of the study was that the reductions of low-density lipoprotein, lipoprotein (a), and fibrinogen and the correction of the acid-base balance were comparable with the results of the standard system. As a second step, the HELP Futura system was evaluated in a clinical acceptance test and in a field test in the daily routine. After approximately 2,000 treatments on 35 patients, we can conclude that the HELP Futura procedure has reached a mature phase with a high degree of clinical safety and flexibility. PMID- 11778927 TI - Powdered sorbent liver dialysis and pheresis in treatment of hepatic failure. AB - The Liver Dialysis Unit (the Unit) is a liver-assist device that employs hemodiabsorption (dialysis of blood against powdered sorbents) to selectively remove numerous small molecular weight toxins of hepatic failure. The Unit has been cleared by the Food and Drug Administration and is indicated and marketed for treatment of acute hepatic encephalopathy (AHE) due to decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective, and randomized studies of liver dialysis were conducted at several centers, enrolling 56 patients with AHE, grades II-IV with or without renal and respiratory insufficiency or failure. Liver dialysis treatments were for 6 h daily, 1-5 days with similar observation periods for control patients. Physiologic status, neurologic status, and outcome (recovery of hepatic function, improvement for transplant, or death) were measured, and results were compared for treated patients versus controls for patients with A-on-C and patients with FHF. Liver dialysis resulted in physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, 35.7% control, p = 0.036), but had an insignificant improvement in the outcome of patients with FHF as compared with the control group. Among the overall 31 treated patients, 51.6% survived. Outcome was not negatively affected by the presence of kidney failure or respiratory failure. The plasmafilter unit (PF-Unit) combines hemodiabsorption with push-pull sorbent-based pheresis (the PF add-on module, with powdered sorbent surrounding plasmafilters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25 ml/min. The PF Unit has been tested in a few patients with hepatic failure with Grades III and IV encephalopathy, and respiratory, and kidney insufficiency. Treatment appeared to be safe, and there were no significant hematologic changes. Physiologic changes included improved blood pressure, and encephalopathy, and stable urine output. Chemical changes included a decrease in the plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and IL-1beta. The PF add-on module adds the capability to the Unit to remove bilirubin and other strongly protein bound toxins from treated patients and may be of clinical benefit in the management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis. PMID- 11778928 TI - Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system. AB - Recently, significant improvement of renal function and prolongation of survival were reported in hepatorenal syndrome (HRS) patients treated with the Molecular Adsorbent Recirculating System (MARS). As no impact on extrarenal organ function was documented, this trial looked into multiple organ function changes during MARS in HRS patients. Eight HRS patients (4 male, mean age 42.1 years, range 30 58, all United Network for Organ Sharing [UNOS] status 2A) were treated intermittendly 4-14 times (total 47, mean 5.9 +/- 3.4) between 4 and 8 h/single treatment. The following changes were observed pre- and posttreatment: bilirubin 466 +/- 146 to 284 +/- 134 micromol/L, creatinine 380 +/- 182 to 163 +/- 119 micromol/L, urea 26.4 +/- 10.3 to 12.9 +/- 4.9 mmol/L, plasma sodium 127.5 +/- 7.7 to 137.5 +/- 4.8 mmol/L (all p < 0.01). Mean arterial pressure (MAP) increased from 71.9 +/- 12.8 to 95.6 +/- 7.8 Torr (p < 0.001). Oliguria or anuria, present in all patients, was successfully reverted. Ascites, present in all patients, was not detectable after the treatment period. The hepatic encephalopathy grade decreased from 2.8 +/- 0.8 to 0.8 +/- 0.7 (p < 0.0001). Child-Index decreased from 13.25 +/- 1.3 to 9.4 +/- 1.8 (p < 0.001). The hospital survival rate was 62%. One man underwent successful liver transplantation 18 months after the treatment. We conclude that MARS can improve multiple organ functions in patients with HRS. PMID- 11778929 TI - Use of human preconditioned phagocytes for extracorporeal immune support: introduction of a concept. AB - Neutrophils are critical effector cells in humoral and innate immunity and play a vital role in phagocytosis and bacterial killing. If they and/or their specific functions are lacking, then immunoparalysis may occur, and severe diseases like systemic inflammatory response syndrome (SIRS) or sepsis can take a fatal course. In this paper, we discuss the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. A human promyelocytic cell line was stimulated for different times with all-trans retinoic acid. The resulting cells displayed major signs and functions of mature neutrophilic granulocytes including oxygen radical production, phagocytosis of living and dead Escherichia coli, Staphylococcus aureus, Candida albicans, intracellular killing, and interleukin production. The cells can be expanded to yield a sufficient cell mass, and subsequent prestimulation results in an expression of specific neutrophil functions. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis-associated diseases like SIRS or sepsis. PMID- 11778930 TI - Development of affinity microparticles for extracorporeal blood purification based on crystalline bacterial cell surface proteins. AB - In this article, the development of specific adsorbents for extracorporeal blood purification are described. Affinity microparticles were prepared by linking Protein A to crystalline cell surface layers (S-layers) from Thermoanaerobacter thermohydrosulfuricus 1111-69. S-layers were used in the form of cell wall fragments obtained by breaking whole cells by ultrasonification, resulting in cup shaped structures (average size 0.5 x 1 microm) completely covered with S-layer protein. Protein A was covalently bound to carboxylic acid groups of the S-layer protein after activation with 1-ethyl-3,3'(dimethylamino)propylcarbodiimide. In batch adsorption experiments with fresh frozen human plasma, the resulting S layer based affinity microparticles showed a high adsorption capacity for IgG (40 mg IgG were bound per g wet pellet of S-layer based affinity microparticles). Fractions eluted from the microparticles were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. They contained only IgG demonstrating that adsorption was specific. In biocompatibility tests, preparations of the S-layer microparticles showed no low-density lipoprotein-reactivity, no cytotoxicity, and no cytokine inducing activity. PMID- 11778931 TI - Tandem plasmapheresis and hemodialysis. AB - Many patients requiring plasmapheresis (PE) have renal failure and also need hemodialysis. If done separately almost 6-7 h is required. Hence, we decided to perform the procedures simultaneously in those patients requiring both PE and hemodialysis. The plasmafilter was inserted into the extracorporeal circuit after the hemodialyzer. A total of 8 such sessions of tandem PE and hemodialysis were performed in 2 patients. This is called tandem PE/hemodialysis. The total procedure was completed in the same time as is required for routine hemodialysis. The total amount of priming fluid is also less when PE and hemodialysis are performed separately. Thus, it is economically beneficial to the hospital and also convenient to the patient. Apart from transient episodes of hypotension, which were corrected by saline infusion, no other complications were noted. PMID- 11778932 TI - P-stable eighth algebraic order methods for the numerical solution of the Schrodinger equation. AB - A P-stable method of algebraic order eight for the approximate numerical integration of the Schrodinger equation is developed in this paper. Since the method is P-stable (i.e. its interval of periodicity is equal to (0, infinity)), large step sizes for the numerical integration can be used. Based on this new method and on a sixth algebraic order P-stable method developed by Simos (Phys. Scripta 55 (1997) 644-650), a new variable step method is obtained. Numerical results presented for the phase-shift problem of the radial Schrodinger equation and for the coupled differential equations arising from the Schrodinger equation show the efficiency of the developed method. PMID- 11778933 TI - A subset-orientated algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries. AB - Libraries of cyclic peptides are being synthesized using combinatorial chemistry for high throughput screening in the drug discovery process. This paper describes the min_syn_steps.cpp program (available at http://www.imb.uq.edu.au/groups/smythe/tran), which after inputting a list of cyclic peptides to be synthesized, removes cyclic redundant sequences and calculates synthetic strategies which minimize the synthetic steps as well as the reagent requirements. The synthetic steps and reagent requirements could be minimized by finding common subsets within the sequences for block synthesis. Since a brute-force approach to search for optimum synthetic strategies is impractically large, a subset-orientated approach is utilized here to limit the size of the search. PMID- 11778934 TI - The study on automorphism group of ESESOC. AB - It is necessary to generate the automorphism group of a chemical graph in computer-aided structure elucidation. In this paper, an algorithm was developed by the all-paths topological symmetry algorithm to build the automorphism group of a chemical graph. A comparison of several topological symmetry algorithms reveals that the all-paths algorithm (APA) could yield the correct class of a chemical graph. It lays a foundation for the ESESOC system in computer-aided structure elucidation. PMID- 11778935 TI - Numerical analysis of Horvath-Kawazoe equation. AB - A new Determining Horvath-Kawazoe (DHK) program for the evaluation of pore-size distribution curve based on the HK method (J. Chem. Eng. Jpn. 16 (1983) 470) is described. The standard bisection procedure (Gerald, C.F., 1977. Applied Numerical Analysis, 2nd ed. Addison-Wesley, CA) is used as a kernel in the proposed algorithm. The calculation of the effective pore-size distribution and the comparative analysis with the previous data published by Horvath and co workers (J. Chem. Eng. Jpn. 16 (1983) 470; Fraissard, J., Conner, C.W., 1997. Physical Adsorption: Experiment, Theory and Applications. Kluwer Academic, London) and recalculated by Do (Do, D.D., 1998. Adsorption Analysis: Equilibria and Kinetics. Imperial College Press, London) were done. PMID- 11778936 TI - Theoretical study of the morphologically originated noise associated with the transmittance of a precipitation system. AB - In this paper we present the results of a computational study that analyses the relationship between the noise associated with the optical transmittance of a system of particles and the morphology of such particles. Computational algorithms have been developed in order to represent the different morphologies within a wide range of sizes. By using this methodology, it has been possible to study the morphology of particles in a virtual system, therefore avoiding the distortions that would inevitably be present in a real system. As a consequence of this study, a classification of the morphologies observed has been made according to the amount of noise they would add to the transmittance of a system of particles. The theoretical results obtained are in good agreement with the available experimental data obtained in real systems. PMID- 11778937 TI - Differential fraction-based kinetic model for simulating hydrodesulfurization process of petroleum fraction. AB - A differential fraction-based kinetic model (DFKM) was proposed to simulate the reaction process in view of the extremely large number of compounds in the petroleum fraction. The results of the simulation experiment on the hydrodesulfurization (HDS) process demonstrated that without considering the exact compounds, DFKM can depict the reaction processes not only of the whole petroleum fraction but of any narrow cut we are interested in. Apparently, this kind of ability, which can be considered as the 'zoom in/out' function, is very useful for the further study on the processing techniques of the petroleum fraction. In the meantime, different methods for obtaining the functions needed in DFKM were investigated and satisfactory results were presented. PMID- 11778938 TI - The extended version of the computer package CST for conversions, standardization and transformations of the spin Hamiltonian and the crystal-field Hamiltonian. AB - The computer package CST (Conversions, Standardization and Transformations) is useful for general manipulations of the zero-field splitting (ZFS) and crystal field (CF) parameters for various systems, especially for transition ions at orthorhombic and lower symmetry sites in crystals. The ZFS parameters are extensively used in the EMR and related spectroscopic and magnetic studies (e.g. magnetic susceptibility, magnetic anisotropy, Mossbauer spectroscopy), whereas the CF parameters in optical absorption spectroscopy, inelastic neutron scattering, and infrared spectroscopy. An extended version of the CST package developed recently is presented in this paper. The standardization, including the standardization errors, for the five possible non-standard ranges of the 'rhombicity' parameter for monoclinic and triclinic symmetry in the local axis system has been worked out. The handling of the border points in the standardization module has been improved. The rotational invariants used before only for the transformations of the CF parameters have been incorporated into the standardization module for the CF and ZFS parameters expressed in any of the major tensor operator notations. The input option in the Euler angles has been added into the transformation module, and the newest physical constants in the unit conversions module have been adopted. Specific applications of the CST package for the CF and ZFS parameters will be presented elsewhere. PMID- 11778939 TI - Radial basis function neural network based QSPR for the prediction of critical pressures of substituted benzenes. AB - The Quantitative Structure-Property Relationship (QSPR) method is used to develop the correlation between structures of a great number of substituted benzenes and their critical pressure. Molecular descriptors calculated from structure alone were used to represent molecular structures. A subset of the calculated descriptors selected using forward stepwise regression was used in the QSPR model development. Multiple Linear Regression and Radial Basis Function Neural Networks are utilized to construct the linear and non-linear prediction model, respectively. To obtain good prediction ability, both topological structure and training parameters of radial basis function neural networks are optimized. The prediction result agrees well with the experimental value of these properties. PMID- 11778940 TI - Theoretical study of the internal rotational barriers in nitrotoluenes, nitrophenols, and nitroanilines. AB - The molecular geometries and internal rotational barriers of the nitro group of 3 nitrotoluene (3-NT), 4-nitrotoluene (4-NT), 3-nitrophenol (3-NP), 4-nitrophenol (4-NP), 3-nitroaniline (3-NA), and 4-nitroaniline (4-NA) were calculated by five different types of density functional theory (DFT) methods with three different levels of basis sets. Analyses of the torsional angles of the nitro, methyl, amino, and hydroxyl groups indicate that 3-NP, and 4-NP are planar molecules, but 3-NT, 4-NT, 3-NA, and 4-NA are not planar molecules. Internal rotational barriers of the nitro group were calculated as the V2 barrier, and the NO2 torsional potentials for each molecule were given. The heights of the V2 barrier vary with the DFT methods, the basis sets, and the kinds and positions of substituents. The average values of the V2 barriers for 3-NT, 4-NT, 3-NP, 4-NP, 3-NA, and 4-NA are 6.44, 6.92, 6.64, 7.93, 6.38, and 9.13 kcal/mol, respectively. Torsional potentials of the OH and NH2 groups of nitrophenol and nitroaniline derivatives were also studied by a B3LYP/6-31G* approach. Except for the OH group in 2-NP, these derivatives have the V2 barrier. PMID- 11778942 TI - Estimation of the chemical rank for the three-way data: a principal norm vector orthogonal projection approach. AB - A new approach for estimating the chemical rank of the three-way array called the principal norm vector orthogonal projection method has been proposed. The method is based on the fact that the chemical rank of the three-way data array is equal to one of the column space of the unfolded matrix along the spectral or chromatographic mode. A vector with maximum Frobenius norm is selected among all the column vectors of the unfolded matrix as the principal norm vector (PNV). A transformation is conducted for the column vectors with an orthogonal projection matrix formulated by PNV. The mathematical rank of the column space of the residual matrix thus obtained should decrease by one. Such orthogonal projection is carried out repeatedly till the contribution of chemical species to the signal data is all deleted. At this time the decrease of the mathematical rank would equal that of the chemical rank, and the remaining residual subspace would entirely be due to the noise contribution. The chemical rank can be estimated easily by using an F-test. The method has been used successfully to the simulated HPLC-DAD type three-way data array and two real excitation-emission fluorescence data sets of amino acid mixtures and dye mixtures. The simulation with added relatively high level noise shows that the method is robust in resisting the heteroscedastic noise. The proposed algorithm is simple and easy to program with quite light computational burden. PMID- 11778941 TI - Artificial neural network model for predicting protein subcellular location. AB - The function of a protein is closely correlated to its subcellular location. Is it possible to utilize a bioinformatics method to predict the protein subcellular location? To explore this problem, proteins are classified into 12 groups (Protein Eng. 12 (1999) 107-118) according to their subcellular location: (1) chloroplast, (2) cytoplasm, (3) cytoskeleton, (4) endoplasmic reticulum, (5) extracellular, (6) Golgi apparatus, (7) lysosome, (8) mitochondria, (9) nucleus, (10) peroxisome, (11) plasma membrane and (12) vacuole. In this paper, the neural network method was proposed to predict the subcellular location of a protein according to its amino acid composition. Results obtained through self consistency, cross-validation and independent dataset tests are quite high. Accordingly, the present method can serve as a complement tool for the existing prediction methods in this area. PMID- 11778943 TI - High-order spatial discretisations in electrochemical digital simulation. Part 3. Combination with the explicit Runge-Kutta algorithm. AB - The application of fourth-order finite difference discretisations of the second derivative of concentration with respect to distance from the electrode, in electrochemical digital simulations, is examined further. In the bulk of the diffusion space, a central 5-point scheme is used, and 6-point asymmetric schemes are used at the edges. In this paper, four Runge-Kutta schemes have been used for the time integration. The observed efficiencies, for the Cottrell experiment and chronopotentiometry, are satisfactory, going beyond those for the 3-point scheme. However, it is third-order Runge-Kutta, rather than the fourth-order scheme, which is the most efficient, the two resulting in practically the same errors. This is probably due to the computational procedure where a constant ratio of delta(t)/h2 was used. PMID- 11778944 TI - Scientific commentary. PMID- 11778945 TI - 210Po and 210Pb cycling in a hydrothermal vent zone in the coastal Aegean sea. AB - To quantify the potential enhancement of naturally-occurring 210Po and 210Pb that may result from the high sulfur-reducing and sulfur-oxidizing regimes associated with hydrothermal vents, sinking particles from both inside and outside vent areas and benthic molluscs grazing on or living near bacterial mats in the vent zone were collected off Milos Island (Aegean Sea) and analyzed for their 210Po and 210Pb content. There was no significant difference in the range of 210Po specific activities measured in particulate material collected by sediment traps in a control area and in the vent area; the resultant 210Po levels were of the same order of magnitude as literature values reported for other Mediterranean coastal areas. 211Pb levels in sinking particles from the control site tended to be higher than those measured in the vent zone, as demonstrated by the lower 210Po/210Pb ratios observed in particles from the control site. Nevertheless, these 210Pb levels were also comparable with similar 210Pb data reported for the northwestern Mediterranean Sea. The 210Po and 210Pb vertical particulate fluxes were, on average, higher in the vent zone as a consequence of the higher particle flux. This observation indicates that vents can indirectly control the flux of these natural radionuclides by affecting the types and amount of particles produced in hydrothermal areas. The 210Po levels measured in a gastropod and a bivalve living on or near the microbial mat in the vent zone were higher than values reported for non-vent gastropods and bivalves from the NW Mediterranean Sea, an observation which suggests that an enhanced food chain transfer of 210Po may occur in the vicinity of vents off Milos Island. Nevertheless, the lack of a general enhancement of 210Po and 210Pb in the marine particulate samples collected indicates that any input of these radionuclides through venting activity may have a minimal effect in the surrounding environment. PMID- 11778946 TI - Catchment characteristics controlling the mobilization and potential toxicity of aluminium fractions in the catchment of the River Dee, northeast Scotland. AB - Elevated streamwater concentrations of aluminium have been associated with the onset of acidification, both by natural and anthropogenic means. This has important implications for river water quality. Concentrations of total, labile inorganic and non-labile-organic fractions of aluminium were determined across the River Dee catchment, northeast Scotland. Fifty-nine subcatchments, chosen to reflect the variety of soils, parent materials and land use patterns across this major river system were sampled bi-weekly for 1 year. The distribution of aluminium was closely linked to factors of parent material and organic soil cover. Strong spatial and temporal relationships were observed between pH and all fractions of aluminium. Significant episodic peaks in aluminium occurred, these being especially pronounced when a storm event followed a period of dry weather. A weathering rate index utilizing the Na dominance of base cations was found to be a predictor of potential streamwater toxicity implied through Ca/inorganic aluminium ratios. It was demonstrated that Al was mobilized from acid headwater streams, whilst concentrations in the main stem remained much lower. PMID- 11778947 TI - Organochlorine accumulation and stable isotope ratios in an Atlantic salmon (Salmo salar) population from the Baltic Sea. AB - We investigated the organochlorine accumulation (p,p'-DDE and sigmaPCB) and stable isotope ratios (N and C) in a migrating salmon (Salmo salar) population in the Baltic Sea. delta15N in the entire population ranged from 11.7 to 13.7 per thousand and delta13C ranged from -22.0 to - 19.6 per thousand. In the entire population, delta15N were weakly related to p,p'-DDE and sigmaPCB concentrations (r2 = 0.20 and 0.14, respectively). However, lipid content was a better predictor of organochlorine (OC) concentrations (r2 = 0.48 and 0.50, respectively). Lipid adjusted sigmaPCB concentrations were not related to delta15N, and lipid adjusted p,p'-DDE concentrations were only weakly related (r2 = 0.12). We divided the salmon population into three groups representing reproductive strategies: small males < 5 kg (SM); large males > 5 kg (LM); and females (F). delta15N varied between the three reproductive strategies. The mean delta15N for SM was 12.7+/ 0.3 per thousand, for F was 12.9+/-0.3 per thousand, and for LM equalled 13.2+/ 0.3 per thousand. Lipid adjusted OC concentrations differed between the three reproductive strategies, with the females having the highest concentrations. We conclude that the delta15N varied between reproductive strategies indicating differences in prey choice, but the lipid content was better able to predict OC concentrations than the trophic position of the salmon. PMID- 11778948 TI - In vitro suppression of thymocyte apoptosis by metal-rich complex environmental mixtures: potential role of zinc and cadmium excess. AB - Excessive amounts of heavy metals (e.g. Zn, Cu, Mn, Cr) are accumulated in river bottom sediments (RBS), being available to humans and animals along food chains. Increased exposure of mammals to certain metals (Cr, Cu) induces immunosuppresion, due to DNA damage and decreased survival of lymphoid cells. By contrast, excess of Zn and Cd causes inhibition of apoptosis thus suggesting increased survival of genetically mutated cells and higher cancer risks in exposed populations. Rat thymic lymphocytes represent a well-established model for apoptosis testing. The primary goal of our study was to assess the degree of apoptosis modulation with a number of RBS extracts differing in their metal contents. A series of freshly deposited RBS was collected at nine sampling stations along the Elbe River. All sediments were rich in Fe, Mn and Zn. The contents of Cu, Cr, Ni, Cd, Hg, Pb and As were much lower and interrelated. The short-term cytotoxicity of aqueous sediment extracts was assessed, using the following criteria: total cell counts; incidence of apoptosis and necrosis (morphological detection by fluorescent microscopy); and nuclear chromatin decay (by DNA flow cytometry). RBS extracts produced both apoptosis and necrosis of thymocytes. High contents of zinc and other heavy metals in the samples correlated with decreased thymocyte apoptosis (r= -0.543 to -0.608, P <0.01). The rates of thymocyte damage showed a distinct dependence on the time and region of sampling. Apoptosis modulation was also tested with pure salts of Mn(II), Zn(II), Cu(II), Cr(III) and Cd(II), at the test concentrations of 1, 10 and 100 microM. Cu(II) and Cr(III) proved to induce marked dose-related apoptosis, whereas Zn(II) ions caused significant suppression of apoptosis. These effects were similar to those trends observed with metal-rich sediments. In the present study. DNA flow cytometry proved to be a less sensitive index of cell death than morphological assay of apoptosis and/or necrosis. In summary, inhibition of lymphocyte apoptosis by RBS extracts and pure metals is associated with excess of zinc and, probably, cadmium. The proposed model of lymphoid cell apoptosis is a promising tool for screening cytotoxic effects of complex environmental samples. PMID- 11778949 TI - Cadmium and lead contents in rice and other cereal products in Japan in 1998 2000. AB - Cereals, especially rice, are a major source of cadmium (Cd) intake for general Japanese populations. In 1998-2000, rice (polished), bread (loaf), noodle and (wheat) flour samples (4113 samples in total) were collected in 63 cities all over Japan, and analyzed for Cd by inductively-coupled plasma mass spectrometry. Another pollutant element of lead (Pb) was determined in parallel. The grand geometric mean for Cd in polished raw (uncooked) rice was 50 ng/g, whereas it was 19 ng/g for flour. The value for Pb was 2-3 ng/g in rice and flour. Calculation for daily Cd intake via rice, taking advantage of the present findings on Cd contents in rice and wheat together with administrative area-specific daily consumptions of rice and wheat showed that Cd via rice is much more than Cd via wheat and that Cd via rice is highest in an area alongside the sea of Japan among the whole country, the observation being in agreement with the results from a previous food duplicate-based field survey. PMID- 11778950 TI - Lead poisoning in Indian silver refiners. AB - The refining of silver from old silver ornaments, articles and jeweller's waste by smelting these with lead scraps for the fabrication of new jewellery is an important small scale industry in India. The present survey and clinical investigations have shown that 31 out of 50 silver refiners with a mean blood lead level of 32.84+/-1.78 microg/dl (range 20.3-64.9), decrease in blood delta aminolevulinic acid dehydratase (ALAD) activity and thiamine (as pyruvate) level and an enhanced urinary excretion of ALA as compared to control, were suffering from lead poisoning. Most of these workers have shown anaemia, abdominal colic, blue lining of gum and muscular wasting indicative of lead toxicity. Twenty-four workers with relatively high blood lead levels were equally divided into two groups and given either vitamin B1 (75 mg, once a day) or vitamin C (250 mg. twice a day) for 1 month. The treatment with both the vitamins significantly lowered the blood lead levels and reduced blood thiamine and copper deficiency. In addition, vitamin C was also effective in reversing the inhibition of blood ALAD activity while the effect of vitamin B1 on its activity was marginal. The daily intake of vitamin B1 and vitamin C may prevent the accumulation of lead and reduce its toxic effects particularly in those regularly exposed to lead. PMID- 11778951 TI - Influence of life-history parameters on organochlorine concentrations in free ranging killer whales (Orcinus orca) from Prince William Sound, AK. AB - Certain populations of killer whales (Orcinus orca) have been extensively studied over the past 30 years, including populations that use Puget Sound, WA, the inside waters of British Columbia, Southeastern Alaska and Kenai Fjords/Prince William Sound, Alaska. Two eco-types of killer whales, 'transient' and 'resident', occur in all of these regions. These eco-types are genetically distinct and differ in various aspects of morphology, vocalization patterns, diet and habitat use. Various genetic and photo-identification studies of eastern North Pacific killer whales have provided information on the male-female composition of most of these resident pods and transient groups, as well as the approximate ages, reproductive status and putative recruitment order (birth order) of the individual whales. Biopsy blubber samples of free-ranging resident and transient killer whales from the Kenai Fjords/Prince William Sound, AK region were acquired during the 1994-1999 field seasons and analyzed for selected organochlorines (OCs), including dioxin-like CB congeners and DDTs. Concentrations of OCs in transient killer whales (marine mammal-eating) were much higher than those found in resident animals (fish-eating) apparently due to differences in diets of these two killer whale eco-types. Certain life-history parameters such as sex, age and reproductive status also influenced the concentrations of OCs in the Alaskan killer whales. Reproductive female whales contained much lower levels of OCs than sexually immature whales or mature male animals in the same age class likely due to transfer of OCs from the female to her offspring during gestation and lactation. Recruitment order also influenced the concentrations of OCs in the Alaskan killer whales. In adult male residents, first-recruited whales contained much higher OC concentrations than those measured in non-first-recruited (e.g. second recruited, third recruited) resident animals in the same age group. This study provides baseline OC data for free ranging Alaskan killer whales for which there is little contaminant information. PMID- 11778952 TI - Gaseous and particulate air pollutants in the Northeastern Mediterranean Coast. AB - The concentrations of sulfur dioxide (SO2), ammonia (NH3) and particulate matter were measured for a 6-month period and the concentration of gas phase nitric acid (HNO3) was measured for a 1-month period in the North-eastern Mediterranean atmosphere (Kucuk Calticak, Antalya) using a 'filter pack' system that was developed and optimised in our laboratory. Among all the gas phase pollutants, HNO3 had the lowest concentration (0.42 microg m(-3)) followed by ammonia. Most of the measured parameters showed variation in time depending on strengths of source regions and meteorological conditions. Nitric acid is found mostly in particulate form, but gas to particulate partitioning of SO2 shows seasonal variation. Wind trajectory analyses indicate that the major contribution to the observed concentrations come mostly from Eastern Europe and Blacksea regions as well as the southern sector. PMID- 11778953 TI - PAH and metal mixtures in New Orleans soils and sediments. AB - The purpose of this study is to determine the degree of PAH contamination and the association of PAHs with inorganic substances in soils and sediments of New Orleans. Bonnet Carre Spillway (BCS) (n = 5) provides modern baseline data, while urban soil samples (CTY) (n = 27) and sediment samples from Bayou St. John (BSJ) (n = 11) provide experimental data for New Orleans. Soil samples were collected from the top 2.5 cm of the surface, air-dried, and sieved (2 mm). Sediments samples were collected with a Wildco-Ekman bottom dredge, air-dried and finely ground. Accelerated solvent extraction (ASE) was used to release PAHs from the samples and analysis was conducted with gas chromatography-mass spectrometry (GC MS). Metals were extracted using a 5:1 ratio of 1 mol/L nitric acid (room temperature) for soil and sediment samples, shaken for 2 h, centrifuged (1000 x g for 15 min) and filtered. Metal analysis was done by inductively coupled plasma atomic emission spectrometry (ICP-AES). Mann-Whitney tests show PAH differences (P < 0.001). Ranking of total PAHs is, BSJ sediments (10.3 mg/kg) > CTY soils (3.7 mg/kg) > BCS alluvium (0.28 mg/kg). The sum of the metals are similar for BSJ sediments (698 mg/kg) and CTY soils (679 mg/kg) and significantly lower for BCS (189 mg/kg). Manganese of these samples is similar for each site. For paired samples, Pearson Product Moment Correlation tests reveal that many PAHs are strongly associated with each other at all locations. For BCS alluvium and BSJ sediments, total PAHs are not significantly associated with total metals. For CTY, most pairs of metals are significantly associated, and total soil PAHs are strongly associated with total soil metals (correlation 0.78, P = 4.9 x 10(-4)). The linear model, total soil PAH = 136.3 + 6.25 (total soil metals) forms the basis for a predicted PAH map of New Orleans. Previous empirical research demonstrates an association between soil lead and children's lead exposure. This study indicates that PAHs are part of the soil mixture of accumulated substances and by-products of industrial society that presents exposure potential in cities. PMID- 11778954 TI - Atmospheric particulate mercury concentration and its dry deposition flux in Changchun City, China. AB - From July 1999 to January 2000, we determined the particulate mercury [Hg(p)] concentration in the atmosphere of five function sites and one contrast site in the city of Changchun, China. During non-heating season, the Hg(p) concentration in air in urban areas ranged from 0.022 to 0.398 ng m(-3) with an average of 0.145 ng m(-3), and at the contrast site with an average of 0.084 ng m(-3). During the heating season, the Hg(p) concentration in urban areas was in the range of 0.148-1.984 ng m(-3) with an average of 0.461 ng m(-3) and with an average of 0.211 ng m(-3) at the contrast site. The Hg(p) concentration during heating season is two times higher than that during non-heating time. Coal burning and wind-blown soil material are the two important sources of Hg(p). Wind blown soil material contributes 7.9-38.5% to the Hg(p) with an average of 24.1% in urban area. A theoretical model was used to estimate the dry deposition flux, with results of 43.06 microg m(-2) a(-1) in the urban area and 21.28 microg m(-2) a(-1) at the contrast site. PMID- 11778955 TI - Radioecological survey at selected sites hit by depleted uranium ammunitions during the 1999 Kosovo conflict. AB - A field study, organised, coordinated and conducted under the responsibility of the United Nations Environment Programme (UNEP), took place in Kosovo in November 2000 to evaluate the level of depleted uranium (DU) released into the environment by the use of DU ammunition during the 1999 conflict. Representatives of six different scientific organisations took part in the mission and a total of approximately 350 samples were collected. During this field mission, the Italian National Environmental Protection Agency (ANPA) collected water, soil, lichen and tree bark samples from different sites. The samples were analysed by alpha spectroscopy and in some cases by inductively coupled plasma-source mass spectrometry (ICP-MS). The 234U/238U and 235U/238U activity concentration ratios were used to distinguish natural from anthropogenic uranium. This paper reports the results obtained on these samples. All water samples had very low concentrations of uranium (much below the average concentration of drinking water in Europe). The surface soil samples showed a very large variability in uranium activity concentration, namely from approximately 20 Bq kg(-1) (environmental natural uranium) to approximately 2.3 x 10(5) Bq kg(-1) (approximately 18000 mg kg(-1) of depleted uranium), with concentrations above environmental levels always due to DU. The uranium isotope measurements refer to soil samples collected at places where DU ammunition had been fired; this variability indicates that the impact of DU ammunitions is very site-specific, reflecting both the physical conditions at the time of the impact of the DU ammunition and any physical and chemical alteration which occurred since then. The results on tree barks and lichens indicated the presence of DU in all cases, showing their usefulness as sensitive qualitative bio-indicators for the presence of DU dusts or aerosols formed at the time the DU ammunition had hit a hard target. This result is particularly interesting considering that at some sites, which had been hit by DU ammunition, no DU ground contamination could be detected. PMID- 11778956 TI - Antioxidant enzymes in brackishwater oyster, Saccostrea cucullata as potential biomarkers of polyaromatic hydrocarbon pollution in Hooghly Estuary (India): seasonality and its consequences. AB - Use of antioxidant enzymes as biomarkers often becomes a complicated process at application level because they show considerable seasonal fluctuation due to both natural and biological factors. In this study, we studied the consequences of seasonal variation of antioxidant enzymes [catalase (EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1), glutathione peroxidase (GPX, EC 1.11.1.9) and microsomal NADPH-DT diaphorase (EC 1.6.99.2)] in the digestive gland of wild brackishwatcr oysters, Saccostrea cucullata for biomonitoring against polyaromatic hydrocarbon (PAH) contamination in Hooghly Estuary, north-eastern coast of India. As a general trend, maximum antioxidant enzyme activities were detected in pre-monsoon period or summer (March-June) followed by a gradual decrease during monsoon (July-October) with a minimum in post-monsoon period or winter (November-February) and this pattern was similar to tissue concentrations of PAHs also. The physiological fluctuations of the antioxidant defense systems were inversely-related to the lipid peroxidation indicating an enhanced susceptibility of oyster tissues to oxidative stress during post-monsoon or winter period. However, the oysters from polluted populations exhibited consistent very high PAHs load in their tissues as well as significant increases in the activities of antioxidant enzymes than in non-polluted populations in all three seasons. The results indicated that the antioxidant enzymes, catalase, SOD and microsomal NADPH-DT diaphorase in digestive gland of S. cucullata could be useful biomarkers of PAHs contamination. It also emphasized that seasonal variation of potential biomarkers like such enzymes should be incorporated into interpretation of biomonitoring studies by the use of appropriate controls and identical treatment in analysis of polluted and non-polluted samples. PMID- 11778957 TI - Congener-specific profile and toxicity assessment of PCBs in green turtles (Chelonia mydas) from the Hawaiian Islands. AB - Chemical pollution may play a role in the etiology of fibropapillomatosis in green turtles (Chelonia mydas). In this preliminary study, polychlorinated biphenyls (PCBs) were measured in the livers and adipose fats of green turtles collected after they were stranded on Oahu Island, Hawaii in 1992-1993. Average concentrations of total PCBs were 45-58 ng/g dry weight and 73-665 ng/g in the liver and adipose tissues, respectively. Hexachlorobiphenyls were predominant homologues, PCBs 153 and 138 were dominant congeners in all the turtle tissues. Among the most toxic coplanar congeners, in the order of abundance, were PCB 77 > 126 > 169. Estimated toxic equivalents (TEQs) of PCBs to 2,3,7,8 tetrachlorodibenzo-p-dioxin were 8-15 pg/g in the livers and 13-48 pg/g in the adipose tissues. PCB 126 contributed 85-91% of the total TEQs. PMID- 11778958 TI - Effect of organic matter and liming on the reduction of cadmium uptake from soil by triticale and spring oilseed rape. AB - The aim of the study conducted on triticale and spring oilseed rape was to determine the role of liming, brown coal and compost medium in reducing the effect of cadmium contamination (at the rates of 0, 7.5, 15 and 22.5 mg Cd kg(-1) of soil) on yield and chemical composition of the crop. In the series of experiments without liming, a considerable decline in the yield of spring triticale grain, straw, root weight and green mass yield of rape was observed in response to the soil contamination with cadmium. Brown coal and especially compost medium added to soil neutralised the negative effect of cadmium on the grain yield and reduced a decrease in the yield of straw and roots of triticale. Soil liming proved to reduce the yield drop in oilseed rape caused by the contamination of soil with cadmium. The content of cadmium in roots and grain of spring triticale far exceeded that determined in triticale straw. The pollution of soil with cadmium caused a 26-fold increase in the content of this metal in grain, a 10-fold increase in roots of triticale and a twofold in oil-seed rape. Application of compost medium, brown coal and, to a smaller extent, liming reduced the level of cadmium in the parts of triticale brought to investigation. The soil contamination with cadmium caused certain modifications in the content of nitrogen, potassium, magnesium, calcium and sodium in spring triticale and in the content of N-total, potassium and magnesium in spring oilseed rape. PMID- 11778959 TI - Wood-burning appliances and indoor air quality. AB - Wood heating represents an interesting economic alternative to electrical or heating oil and gas systems. However, many people are concerned about poor indoor air quality in homes equipped with wood-burning appliances. We conducted a study in the Quebec City region (Canada) to verify the extent of indoor air contamination, and to examine the frequency of respiratory symptoms and illnesses among occupants of wood-heated homes. One child attending primary school (median = 8 years old; range = 5-14 years old) and an adult (median = 37 years old; range = 23-52 years old) were recruited in each eligible house. Eligible houses were without known sources of combustion products (smokers, attached garage, oil or gas furnace, gas stove, etc.) except for wood-burning appliance. Out of the 89 houses included in the study, 59 had wood-burning appliances. Formaldehyde, nitrogen dioxide, respirable particles (PM10) and carbon monoxide were measured in a sub-set of 49 houses (41 with a wood-burning appliance and 8 without). The frequency of respiratory symptoms and diseases among participants were documented using a daily symptom diary. Concentrations of contaminants were low in most houses, both with or without a wood-burning appliance. Globally, there was no consistent relationship between the presence of a wood-burning appliance and respiratory morbidity in residents. Nevertheless, residents who mentioned being exposed to fumes emitted by such an appliance reported more respiratory illnesses and symptoms. The presence of animals or molds, and keeping windows closed most of the time in winter were other factors associated with respiratory problems. We conclude that wood burning appears to be a respiratory health risk for occupants if the appliance is not maintained and used properly. PMID- 11778960 TI - Depleted uranium (DU): a holistic consideration of DU and related matters. AB - Following the use of depleted uranium (DU) during the Gulf and Balkan conflicts, unnecessary and costly confusion has existed for some 11 years concerning the hazard it constitutes, despite the fact that sufficient data are available to answer most of the relevant questions. In tracing the significance of uranium in the environment and humans, too much reliance is still placed upon the extrapolation of animal data. The existing radiological nomenclature is far too involved and complex to understand, let alone implement. The excellence of early health physics seems to have been lost, and hence there is a failure to utilise the large body of knowledge, and the manner in which it was obtained, in other disciplines. Health physics has failed to understand the nature of some natural processes that ultimately control radiation dose to the environment and humans. Examination of three types of DU, in particular the highly radioactive and potentially hazardous unprocessed, spent-reactor uranium fuel debris (UDU), alluded to as hot particles, has been poorly studied on the basis of scarcity in the environment. Fundamental geological processes are described which illustrate that, as a consequence of routine operation of nuclear reprocessing plants, especially in the past, and following reactor accidents, natural processes can result in an enrichment of DU particles in most types of sediment. Failure to grasp essential geological processes in relation to the dispersion of radionuclides in the environment is detrimental to public acceptance of an essential form of energy in association with others. PMID- 11778961 TI - Metal content of dandelion (Taraxacum officinale) leaves in relation to soil contamination and airborne particulate matter. AB - The global distribution of the common dandelion (Taraxacum officinale Weber, sensu lato; Asteraceae), along with its ability to tolerate a wide range of environmental conditions, make this 'species' a particularly attractive candidate to evaluate for its value as a biological monitor of environmental metal contamination. To examine the metal content of dandelion leaves in relation to environmental metal levels, the concentrations of eight metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) were analyzed in leaf and soil samples collected at 29 sites in the mid-western United States differentially impacted by pollution. Sites were chosen primarily to cover a range of annual mean 24-h airborne particulate matter < or = 10 microm (hereafter, PM10) exposure, with PM10 levels varying from those found in isolated rural areas to levels typical of the most industrialized urban locations in the mid-western United States. A positive. significant correlation was detected between soil concentrations of each metal and measures of PM10 at a site, signifying that airborne particulate matter is a good indicator of soil metal contamination. Leaf concentrations of four of the eight metals (Cr, Mn, Pb and Zn) examined were found to increase significantly as the soil levels of these metals increased, but the percentage of the total variation explained by the relationship in these cases was generally low. This latter finding, along with the lack of a significant relationship between leaf and soil concentrations for the four other metals, indicate that the factors affecting metal absorption from the soil by dandelions are complex and that, aside from soil metal concentrations, other soil, plant and/or other environmental factors affect metal uptake. There was also no evidence that leaf metal concentrations were positively correlated with PM10. In addition, the concentrations of some metals (Cu, Fe, Mn, Pb and Zn) were significantly higher in leaves collected in the fall compared to those collected at the same sites in the spring. These findings suggest that dandelions may not be a particularly effective tool for quantifying levels of environmental metal contamination, at least on the scale of pollution typifying industrialized urban areas of the mid-western United States. PMID- 11778962 TI - Effects of bulk precipitation pH and growth period on cation enrichment in precipitation beneath the canopy of a beech (Fagus moesiaca) forest stand. AB - The effects of bulk precipitation pH and growth period (growing and dormant) on cation enrichment beneath foliage were examined in a beech (Fagus moesiaca) forest stand during a 48-month period. The bulk precipitation pH values ranged from 4.2 to 7.2. The lowest values were observed in winter due to fossil fuel combustion in a nearby big city. The ratio of monthly ion fluxes of throughfall plus stemflow over monthly ion fluxes of bulk precipitation was chosen as an index of cation enrichment and, therefore, as the dependent variable. Bulk precipitation pH and growth period were chosen as independent factors. Precipitation interception (%) by tree canopies was also taken into account. It was found that the pH factor was significant only for H+ ion enrichment suggesting neutralization of H+ ions in the beech canopy, whereas Mg2+ and K+ enrichment were greater in the growing period, probably as a result of leaching. Crown interception was negatively significant for NH4+-N enrichment. PMID- 11778963 TI - Concentrations of heavy metals and plant nutrients in water, sediments and aquatic macrophytes of anthropogenic lakes (former open cut brown coal mines) differing in stage of acidification. AB - Concentration of heavy metals (Al, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, V and Zn) as well as macronutrients (N, P, K, Ca, Mg, S) were measured in water, bottom sediments and plants from anthropogenic lakes in West Poland. The collected plants were: Phragmites australis, Potamogeton natans, Iris pseudoacorus, Juncus effusus, Drepanocladus aduncus, Juncus bulbosus, Phalaris arundinacea, Carex remota and Calamagrostis epigeios. Two reference lakes were sampled for Nymphaea alba, Phragmites australis, Schoenoplectus lacustris, Typha angustifolia and Polygonum hydropiper. These plants contained elevated levels of Cd, Co, Cr, Cu and Mn, and part of the plants contained in addition elevated levels of Mn, Fe, Pb, Ni and Zn. Analyses of water indicated pollution with sulfates, Cd, Co, Ni. Zn, Pb and Cu, and bottom sediments indicated that some of the examined lakes were polluted with Cd, Co and Cr. Strong positive correlations were found between concentrations of Co in water and in plants and between Zn in sediments and plants, indicating the potential of plants for pollution monitoring for this metal. Heavy metal accumulation seemed to be directly associated with the exclusion of Ca and Mg. PMID- 11778964 TI - Multivariate outlier detection and remediation in geochemical databases. AB - In this study, outliers are classified into three types: (1) range outliers; (2) spatial outliers; and (3) relationship outliers, defined as observations that fall outside of the values expected from correlation within the dataset. The multivariate methods of principal component analysis (PCA), multiple regression analysis (MRA) and an autoassociation neural network (AutoNN) method are applied to a dataset comprising 203 samples of rare earth element (REE) concentrations in soils of Jamaica which shows the expected good correlations between the elements. PCA is shown to be effective in detection of high value range outliers, while AutoNN and MRA are effective in detection of relationship outliers. A backpropagation neural network was used to predict the 'expected values' of the outliers. Four obvious relationship outliers with unexpected low Sm concentrations were selected as an example for remediation. The predicted Sm values were confirmed on remeasurement. Neural network methods, with the advantages of being model-free and effective in solving non-linear relationship problems, appear to provide an automated and effective way for the quality control of environmental databases. PMID- 11778965 TI - Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma. AB - We analyzed 104 patients with non-Hodgkin's lymphoma, follicular or diffuse large B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p = 0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p = 0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p = 0.03) and involvement of more than one extranodal area (p = 0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p = 0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p = 0.02) and LDH (p = 0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p = 0.009). PMID- 11778966 TI - Epirubicin, cisplatin, and prolonged or brief infusional 5-fluorouracil in the treatment of carcinoma of unknown primary site. AB - The cytotoxic regimen of epirubicin, cisplatin, and continuous infusional 5 fluorouracil (ECF) has demonstrated activity in a range of malignancies, including gastroesophageal, breast, and pancreatic cancers. Prolonged infusional central venous catheter (CVC) mediated therapy is not always feasible and modifications of the 5-fluorouracil (5FU) schedule have been reported. We reviewed our experience of both the standard and a modified ECF regimen in patients diagnosed with carcinoma of unknown primary site (CUPS). A retrospective analysis of all patients diagnosed with CUPS (31 adenocarcinoma and 5 poorly differentiated carcinoma) and treated with ECF between June 1994 and June 1998 was undertaken. Thirty-six patients, median age 56 (range: 24-74), were treated thrice-weekly with 50 mg/m2 epirubicin, 60 mg/m2 cisplatin, and 5-FU administered either by continuous infusion 200 mg/m2/d via a CVC (standard ECF) or as a 6-h infusion 600 mg/m2 through a peripheral venous catheter (modified ECF). Thirteen patients were treated with standard ECF and 23 received modified ECF. The median number of cycles administered was 4 (range: 1-10). Thirty-two patients had evaluable disease, seven (22%; 95% confidence interval: 8-36%) demonstrated a partial response, including three patients that received standard ECF and four treated with modified ECF. There were no complete responses. The median survival for all 36 patients was 9.0 mo. Median survival for patients treated with standard ECF was 11.7 mo as compared to 5.1 mo for the modified ECF schedule (p = 0.052). Liver involvement and elevation of serum CA19.9 were identified as possible adverse prognostic factors. Both regimens were well tolerated, with the only grade 3/4 toxicity recorded being leukopenia (four patients), nausea/vomiting (seven patients), and diarrhea (one patient). CVC complications in the standard ECF group were thrombosis (one patient) and infection (three patients). There were no treatment-related deaths. We conclude that ECF, whether modified or standard, has modest activity in the setting of CUPS. Patient survival is comparable to survival documented in previous reports of CUPS treatment. The apparent survival difference between the two ECF schedules may be the result of patient selection factors. The optimal treatment of CUPS remains unknown and can only be determined through randomized controlled trials. PMID- 11778968 TI - Interference of cytokeratin-20 and mammaglobin-reverse-transcriptase polymerase chain assays designed for the detection of disseminated cancer cells. AB - Several reverse-transcriptase polymerase chain reaction (rtPCR) assays have been designed for the detection of disseminated cancer cells. The specificity of these discussed molecular approaches is controversial. Biological interference of the cytokeratin-20 and mammaglobin rtPCR assays has been investigated. Cell lines of different lineages and bone marrow and peripheral stem cells from patients without epithelial cancer have been examined for the transcription of the cytokeratin-20 (CK20) and mammaglobin messages prior to and after stimulation with different cytokines in a total of 370 liquid cultures. Amplification of both messages from clinical samples prior to stimulation does not support the high specificity for the detection of disseminated epithelial cancer cells as reported. Cytokeratin-20 was amplified from the chronic myeloic leukemia (CML) derived line K562. Transcription was not influenced by cytokines, either in cell line experiments or in clinical samples. The thesis of a low-level background transcription in granulocytes is supported. Mammaglobin was induced in cell lines significantly by GM-CSF and in clinical samples additionally by several more cytokines. These results indicate that under certain conditions involving cytokine production, the use of mammaglobin rtPCR for the detection of epithelial cancer cells could be limited. In conclusion, the mechanism of interference of both rtPCR assays are completely different and further research is necessary before the cytokeratin-20 or mammaglobin rtPCR could become standard methods for the detection of disseminated epithelial cancer cells. These factors leading to so-called false-positive results have to be considered in future applications of rtPCR for the detection of minimal residual disease. PMID- 11778967 TI - Apoptosis and cell growth inhibition as antitumor effector functions of interferons. AB - Since their introduction to the clinic some 30 yr ago, interferons (IFNs) have become standard therapy for a range of disorders, including malignant and benign tumors as well as various viral diseases. Although IFNs will induce remissions in some patients with cancer, they are of no benefit or, at best, lead only to minor improvements in the great majority of patients with malignant disease. One of the great challenges of IFN research is to understand the multiple ways by which IFNs influence the behavior of tumor cells and to identify the factors that underlie the resistance of some tumors to IFNs. This review is written with a focus on two anticellular effects of IFN, inhibition of proliferation and induction of apoptosis, possible mechanisms underlying the antitumor action of IFN. In addition, possible reasons for IFN tumor cell resistance are also discussed. PMID- 11778970 TI - Serum levels of IL-1 beta, sIL-2R, IL-6, IL-8, and TNF-alpha in febrile children with cancer and neutropenia. AB - Serum levels of interleukin-1 beta (IL-1beta), soluble interleukin 2 receptors (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) were measured to predict some characteristics of febrile episodes in children with cancer and neutropenia. Forty-eight episodes of febrile neutropenia were determined in 23 pediatric cancer patients, including 35 febrile episodes without identifiable source, 7 episodes of bacteremia due to Gram negative organisms and 4 due to Gram-positive organisms, and 2 fungal infections. Interleukin-6, sIL-2R, and IL-8 levels were significantly higher at the beginning of the febrile episodes than those of controls (p < 0.001, p < 0.001, and p < 0.001). Interleukin-6, slL-2R, and IL-8 levels were higher in patients with bacteremia due to Gram-negative organisms than in those with Gram-positive ones (p = 0.042, p = 0.006, and p = 0.023, respectively). TNF-alpha and IL-1beta levels were similar in febrile episodes and controls (p > 0.05). In conclusion, sIL-2R, IL-6, and IL-8 levels may be helpful in the prediction of infection in febrile cancer patients with neutropenia and measurements of IL-1beta and TNF alpha were not useful for identifying the presence and the type of infection in febrile neutropenic episodes in children. PMID- 11778969 TI - The implication of compromised renal function at presentation in myeloma: similar outcome in patients who receive high-dose therapy: a single-center study of 251 previously untreated patients. AB - The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 micromol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p = 0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p = 0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (beta2M) > or = 3.7 (p < 0.0001), age > or = 52.5 yr (p = 0.002), performance status (PS) > or = 2 (p = 0.005) and patients with light-chain myeloma (p = 0.03) had a significantly shorter OS, beta2M > or = 3.7, PS > or = 2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome. PMID- 11778971 TI - Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate. AB - Derivatives of somatostatin (sms) are attracting increasing interest as part of the treatment of several cancer diseases expressing sms receptors (srs). Radiolabeled sms analogs can additionally be used for systemic radiotherapy and for diagnostic investigations. Glycosylated sms-14 (sms-dextran70) was characterized regarding in vitro srs binding, biodistribution, and blood half life in mice. Rat brain cortex membranes (expressing srs 2) were used for the srs binding study. Tyr3-Octreotide was used as positive control. The binding data were analyzed by competition curve analysis. In the biodistribution study, the Bolton-Hunter reagent was used for the radioiodination of sms-dextran70. Organs and blood were collected at different time-points and the percentage of the injected dose per gram of tissue (%ID/g) was calculated. The conjugate was administered subcutaneously (sc). The sms-dextran70 showed high srs binding affinity (i.e., in the same nanomolar range as the reference ligand Tyr3 octreotide (IC50 approximately 2.5 nM). The blood half-life was approx 27 h after reaching maximum blood concentration 24 h postinjection. Because of the molecular weight of the conjugate (i.e., approx 75,000) being above the kidney threshold for dextran (i.e., 50,000), the digestion and excretion is assumed to be mainly through the hepatobiliary system. Increased uptake was seen in the adrenals, which are receptor-positive organs. Some accumulation was seen in the stomach, indicating certain deiodination of the conjugate label. The sms-dextran70 showed promising properties and its clinical relevance is currently being evaluated in clinical phase I-II studies. PMID- 11778972 TI - Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support. AB - In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22-2.15; p = 0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan prednisone treatment. Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma. PMID- 11778973 TI - Phase II trial of clarithromycin and pamidronate therapy in myeloma. AB - A phase II study to further evaluate any possible antimyeloma activity of clarithromycin was conducted following a report of possible clinical efficacy. Twenty patients, 11 male and 9 female with a median age of 73 yr, received clarithromycin 500 mg twice daily with monthly intravenous infusions of disodium pamidronate. None of the study patients received concomitant cytotoxic or steroid therapy. Ten patients had relapsed disease, five had refractory disease, four were previously untreated, and one patient was unsuitable for cytotoxic therapy. The median number of previous treatment modalities was 1.5. Serum M protein levels and urinary M protein excretion were monitored along with other parameters to assess response. Median duration of therapy was 16 wk and six patients had dose escalation. A significant decrease in M protein production occurred in one patient at wk 12 of therapy, which maximized following dose escalation to a 47% decrease from baseline. Two patients had incremental but unsustained M protein reductions. Serum/urine M protein levels remained static in six patients and rose in the remaining six evaluable patients. The M protein response rates in this study are much lower than those previously reported and do not confirm efficacy. In addition, the recently postulated antimyeloma activity of pamidronate may explain some of the M protein decreases. PMID- 11778974 TI - Health-related quality of life and its potential prognostic implications in patients with aggressive lymphoma: a Nordic Lymphoma Group Trial. AB - This study was conducted to explore treatment and disease-related effects on health-related quality of life (HRQoL) in patients with aggressive lymphoma, to identify predictors for impaired long-term HRQoL, and to analyze the prognostic value of pretreatment HRQoL. Ninety-five patients with aggressive lymphoma, constituting a subset of a randomized multicenter trial comparing CHOP and MACOP B, entered a HRQoL study, using the EORTC QLQ-C30 questionnaire. Patient scores were compared to scores from an age- and gender-adjusted reference population sample, and evaluation of the prognostic value of pretreatment QoL scores in relation to clinical prognostic factors was performed. Before treatment, patients exhibited lower scores of global QoL, physical, role, and social functions, and more appetite loss, compared to the reference population. Role functioning improved compared to baseline, but remained depressed compared to the reference group more than 8 mo after end of treatment. By then, the patient group displayed no difference in other HRQoL variables compared to that of the reference population. No reliable predictor for impaired long-term HRQoL could be identified. In multivariate analysis, including the factors of the International Prognostic Index, pretreatment global QoL was an independent prognostic marker for overall survival. In conclusion, in this population with aggressive lymphoma and favorable prognostic features, HRQoL was not substantially affected during the first year after diagnosis. Pretreatment global QoL may constitute a significant prognostic factor, meriting further investigation in prospective studies. PMID- 11778975 TI - Vinorelbine-associated myelopathy in a patient who previously received paclitaxel: a case report. AB - Vinorelbine seems to cause less neurotoxicity than other vinca alkaloids because of its selective activity on mitotic cells over axonal microtubules. Clinical trials report very mild peripheral neurotoxicity with distal paresthesiae and there are no reports of myelopathy in these series of patients. The authors describe a patient who developed a rare event of myelopathy while on vinorelbine for non-small-cell lung cancer. PMID- 11778976 TI - The evolving practice of genetic counseling. PMID- 11778977 TI - Researching the biology of PXE: partnering in the process. AB - PXE International, a disease advocacy group, plays a central role as a catalyst in several research initiatives focused on the biology, epidemiology, and genetics of pseudoxanthoma elasticum (PXE). These initiatives accelerate research on PXE and provide a basis for several productive collaborative partnerships, including a particularly successful professional relationship between PXE International and the Laboratory of Matrix Pathobiology at the University of Hawaii. This partnership was critical in discovering the PXE gene and in beginning the elucidation of the pathobiology of this genetic disorder. Examination of some of the elements of this partnership may be useful for other lay advocacy/professional collaborations. PMID- 11778978 TI - Facilitating informed choice in prenatal testing: how well are we doing? AB - There is a consensus that prenatal testing services need to provide the information and support necessary for women to make informed choices about prenatal testing. Informed choices are those based on relevant information that reflect the decision-maker's values. To date, most research has focused on the information provided to women deciding whether to undergo tests. This has highlighted the poor quality of information provided to many women. There is agreement on the need to provide information on three key aspects of any test: the condition for which testing is being offered, characteristics of the test, and the implications of testing. Very little research has been conducted on decisions after the diagnosis of a fetal abnormality and how information and emotional and decisional support are and should be provided. Research is now needed in four key areas: first, on the optimal ways of organizing services to facilitate choices that are not only based on relevant information, but also reflect the decision-maker's values; second, on the most effective ways of framing information needed for the different decisions involved in prenatal testing; third, on the most effective media in which to deliver information; and, fourth, to identify aspects of counseling that facilitate informed choices following diagnoses of fetal abnormality. If we value women's ability to make informed choices about prenatal tests as highly as we value reliable laboratory tests, evidence-based quality standards need to be developed for the information and support women are given at all stages of the process of prenatal testing. PMID- 11778979 TI - Process studies in genetic counseling: peering into the black box. AB - Genetic counseling is a dynamic psychoeducational process. Yet we know very little about its interior. Process research explores what transpires between providers and their clients and can serve to provide insight into unknown practice dimensions. The few process studies that have been conducted in genetic counseling provide a glimpse into the Black Box, but more of this type of research is needed to examine the contents. To achieve success with process studies a contemporary definition of genetic counseling is proposed. Thoughtfully designed process studies in genetic counseling will provide the data to refine the definition and identify the components of counseling, the communication process between provider and client, the therapeutic interventions used by counselors, and the needs, attitudes and expectations of clients. Overall, process studies will contribute to a more accurate understanding of the practice of genetic counseling. PMID- 11778980 TI - Does indirect speech promote nondirective genetic counseling? Results of a sociolinguistic investigation. AB - To date, research examining adherence to genetic counseling principles has focused on specific counseling activities such as the giving or withholding of information and responding to client requests for advice. We audiotaped 43 prenatal genetic counseling sessions and used data-driven, qualitative, sociolinguistic methodologies to investigate how language choices facilitate or hinder the counseling process. Transcripts of each session were prepared for sociolinguistic analysis of the emergent discourse that included studying conversational style, speaker-listener symmetry, directness, and other interactional patterns. Analysis of our data demonstrates that: 1) indirect speech, marked by the use of hints, hedges, and other politeness strategies, facilitates rapport and mitigates the tension between a client-centered relationship and a counselor-driven agenda; 2) direct speech, or speaking literally, is an effective strategy for providing information and education; and 3) confusion exists between the use of indirect speech and the intent to provide nondirective counseling, especially when facilitating client decision-making. Indirect responses to client questions, such as those that include the phrases "some people" or "most people," helped to maintain counselor neutrality; however, this well-intended indirectness, used to preserve client autonomy, may have obstructed direct explorations of client needs. We argue that the genetic counseling process requires increased flexibility in the use of direct and indirect speech and provide new insights into how "talk" affects the work of genetic counselors. PMID- 11778981 TI - Multicultural genetic counseling: then, now, and in the 21st century. AB - Scholars, educators, and practitioners have argued that racial-cultural issues are obstacles for those seeking genetic counseling. When available, cross cultural genetic counseling has focused on simplistic knowledge of client health beliefs and cultural customs, professional cultures, and biased theoretical models as reasons for failure to create realistic knowledge of members of racial cultural groups in the United States. Recognizing the importance of meeting the needs for all who seek genetic counseling services, genetic counselors have been providing direction in cross-cultural genetic counseling research, practice, training, and developing competency, ethical, and professional guidelines. However, emanating from a cultural pluralism perspective, cross-cultural genetic counseling has often resulted in homogenized group stereotypes without attention to intragroup variation and individual differences. A transition from cross cultural towards multicultural genetics shifts from culture-specific group norms to an integrated social, historical, psychological, and political perspective. By valuing the process of personal and professional racial-cultural identity development, the evolution from cross-cultural to multicultural genetic counseling that has occurred within the past quarter century is discussed. PMID- 11778982 TI - Genomic medicine: who will practice it? A call to open arms. AB - The Human Genome Project and other recent developments will broaden and increase the importance of genetics in health care. "Clinical genetics" will become "genomic medicine" and will no longer be almost the sole purview of genetic specialists-medical geneticists, genetic counselors, and genetic advanced practice nurses. The changing use of genetics in health care will require the acquisition of new knowledge, skills, and attitudes by many health care professionals who are not genetic specialists. Such health care professionals will not only be necessary to the widespread integration of genetics into clinical care, but they will make unique contributions to this integration that will add to the quality of genomic medicine. This new use of genetics in health care will also allow, even require, new ways of working for genetic specialists, who will continue to occupy unique and vital roles. PMID- 11778983 TI - Empowering primary care health professionals in medical genetics: how soon? How fast? How far? AB - Applications of genetics to the practices of medicine and public health are important today and will only become more compelling as our understanding of the human genome evolves. Because of a perceived lack of medical genetics professionals, it is generally believed that primary health care providers (PCPs) will need to assume prominent roles in delivering clinical genetics services. However, a number of studies indicate that most PCPs are neither well enough educated in genetics nor interested enough in becoming so to effectively contribute. Those who advocate empowering PCPs must be aware of potential problems with any approach thus far suggested for achieving this goal. Moreover, any analysis of this model must consider the potential ramifications for medical genetics professionals, patients, and families. In this article, we explore some of the unique features of the culture of medical genetics services and service providers. We discuss how important this culture is to clinical outcomes and the likelihood that its positive attributes would be preserved in a PCP model of medical genetics service delivery. PMID- 11778984 TI - Categorizing genetic tests to identify their ethical, legal, and social implications. AB - Practice standards in medical genetics provide an implicit guide to the ethical, legal, and social implications (ELSI) of genetic tests. The common use of nondirective counseling reflects the principle that many testing decisions should be determined by personal values. Yet geneticists make test recommendations in some circumstances, e.g., RET mutation testing for MEN2 and newborn screening for phenylketonuria (PKU). Conversely, many geneticists recommend against testing for Apolipoprotein E (ApoE) alleles to predict Alzheimer disease (AD) risk. Taken together, these examples suggest that genetic tests can be categorized by a joint consideration of clinical validity and availability of effective treatment for persons who test positive. For genetic tests with high clinical validity/no treatment (e.g., presymptomatic testing for Huntington disease), the predominant concern is adequate nondirective counseling to ensure an informed, autonomous decision. By contrast, the predominant concern for tests with high clinical validity/effective treatment (e.g., PKU) is assuring access to care for eligible persons. For tests with limited clinical validity/no treatment (e.g., ApoE), recommending against test use can be justified on the principle of avoiding harm. For a fourth category, tests with limited clinical validity/effective treatment (e.g., HFE mutation testing for hereditary hemochromatosis), net benefit is the issue: the balance between potential benefits of treatment and potential harms of genetic labeling must be weighed. Where uncertainty exists concerning both clinical validity and effectiveness of treatment, as in the case of BRCA 1/2 mutation testing, the value of testing may vary according to different testing contexts. This approach to test categorization allows a rapid determination of the predominant ELSI concerns for different kinds of genetic tests and identifies the data most urgently needed for test evaluation. PMID- 11778985 TI - The Euroscan study. PMID- 11778986 TI - Fetal abdominal wall defects--easy to diagnose--and then what? PMID- 11778987 TI - How do we counsel patients carrying a fetus with pleural effusions? PMID- 11778988 TI - Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries. AB - OBJECTIVES: To evaluate the current effectiveness of routine prenatal ultrasound screening in detecting gastroschisis and omphalocele in Europe. DESIGN: Data were collected by 19 congenital malformation registries from 11 European countries. The registries used the same epidemiological methodology and registration system. The study period was 30 months (July 1st 1996-December 31st 1998) and the total number of monitored pregnancies was 690,123. RESULTS: The sensitivity of antenatal ultrasound examination in detecting omphalocele was 75% (103/137). The mean gestational age at the first detection of an anomaly was 18 +/- 6.0 gestational weeks. The overall prenatal detection rate for gastroschisis was 83% (88/106) and the mean gestational age at diagnosis was 20 +/- 7.0 gestational weeks. Detection rates varied between registries from 25 to 100% for omphalocele and from 18 to 100% for gastroschisis. Of the 137 cases of omphalocele less than half of the cases were live births (n = 56; 41%). A high number of cases resulted in fetal deaths (n = 30; 22%) and termination of pregnancy (n = 51; 37%). Of the 106 cases of gastroschisis there were 62 (59%) live births, 13 (12%) ended with intrauterine fetal death and 31 (29%) had the pregnancies terminated. CONCLUSIONS: There is significant regional variation in detection rates in Europe reflecting different policies, equipment and the operators' experience. A high proportion of abdominal wall defects is associated with concurrent malformations, syndromes or chromosomal abnormalities, stressing the need for the introduction of repeated detailed ultrasound examination as a standard procedure. There is still a relatively high rate of elective termination of pregnancies for both defects, even in isolated cases which generally have a good prognosis after surgical repair. PMID- 11778989 TI - Freehand three-dimensional Doppler demonstration of monochorionic vascular anastomoses in vivo: a preliminary report. AB - OBJECTIVES: To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous. DESIGN: Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation. RESULTS: Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information. CONCLUSIONS: Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies. PMID- 11778990 TI - Detailed three-dimensional fetal echocardiography facilitated by an Internet link. AB - OBJECTIVES: To assess whether a complete virtual cardiological examination can be achieved in stored three-dimensional volumes of the fetal heart, transmitted to a tertiary fetal cardiology center via the Internet. METHODS: Thirty sequential normal singleton pregnancies were included in the study. Four cardiac volumes were acquired using a three-dimensional ultrasound system. The volumes were sent via the Internet to a tertiary fetal cardiology center, where a detailed fetal cardiac examination was attempted using the three-dimensional volumetric dataset. RESULTS: The median gestational age was 24 (range, 22-28) weeks. A complete heart examination was accomplished in 23 of 30 cases (76.7%; 95% confidence interval, 58-90%). The four-chamber view and the cardiac situs were seen in all cases. The right ventricular outflow tract was seen in 29 (96.7%) cases and the left ventricular outflow tract in 25 (83.3%) cases. The long-axis view of the aortic arch, superior vena cava, inferior vena cava and pulmonary veins were visualized in more than 80% of cases. The mean time of volume acquisition was 9.5 (standard deviation, 2.3) min and the mean examination time by the fetal cardiologist was 17 (standard deviation, 4.8) min. CONCLUSIONS: These preliminary results demonstrate that a three-dimensional virtual examination of the fetal heart is possible. There are limitations such as the lack of flow and functional information but complete ascertainment of the main cardiac connections was possible in the majority of cases. The use of an Internet link has major implications, particularly for situations in which the scanning center is geographically remote from the tertiary referral center. PMID- 11778991 TI - Fetal Doppler velocimetry at high altitude. AB - OBJECTIVES: To determine impedance and velocity characteristics of the fetal circulation using Doppler ultrasound, at extremely high altitude (4300 m) in the Peruvian Andes compared to an ethnically similar population at sea level. METHODS: This was a cross-sectional study of 196 women resident at high altitude (Cerro de Pasco, 4300 m above sea level) and 196 women resident at sea level (Lima) with normal singleton pregnancies. Pulsatility index (PI), maximum velocity (Vmax) and minimum velocity (Vmin) in the umbilical artery, the descending aorta, the middle cerebral artery and the ductus venosus were compared between the two populations using fractional polynomial regression analysis. RESULTS: The PI was higher at high altitude than at sea level in the umbilical artery (regression coefficient = 0.112, P < 0.001), and not significantly different in the descending aorta, middle cerebral artery and ductus venosus. Vmax was lower at high altitude than at sea level in all three arterial vessels assessed; Vmin was lower in two: the umbilical artery and the descending aorta. The high-altitude/sea-level ratios for umbilical artery Vmax and Vmin were 0.93 and 0.82, respectively (P < 0.001 for each), the ratios for descending aorta Vmax and Vmin were 0.93 and 0.89, respectively (P = 0.003 and P < 0.001, respectively), and the regression coefficient for the middle cerebral artery Vmax was -2.844 (P = 0.003). There was no significant difference in the middle cerebral artery Vmin or in the ductus venosus Vmax and Vmin. CONCLUSIONS: Despite the lower ambient oxygen at high altitude and an increase in umbilical artery PI, the fetal circulation does not exhibit a 'brain sparing effect'. This and the overall decrease in blood flow velocities in the fetal circulation at high altitude may be due to the increased fetal hematocrit, which will result in increased blood viscosity. PMID- 11778992 TI - Fetal intracranial hemorrhage: is minor maternal trauma a possible pathogenetic factor? AB - OBJECTIVE: The occurrence of fetal intracranial hemorrhage before labor has been repeatedly observed. The aim of this study was to evaluate the sonographic appearance of fetal intracranial hemorrhage in relation to its location. Possible causative factors were also evaluated. DESIGN: Five consecutive cases of fetal intracranial hemorrhage were identified at a single ultrasound unit between 1996 and 1999. In utero magnetic resonance imaging was also performed in four of these cases. Autopsy was performed after pregnancy termination or intrauterine fetal death (one case of each), and neurological follow-up was initiated in the three surviving infants. RESULTS: Hydrocephaly was the predominant sonographic finding associated with intraventricular or subependymal hemorrhage; sonography provided the correct diagnosis in the former (two cases), whereas magnetic resonance imaging was necessary in the latter. Massive intraparenchymal hemorrhage was depicted as an irregular echoic mass, whereas extradural hemorrhage had a cystic appearance. History of minor maternal physical trauma without maternal or placental injury was elicited in all cases. Ultrasound examinations performed before or shortly after the trauma were available in all cases and showed normal fetal anatomy. CONCLUSIONS: The sonographic appearance of fetal intracranial hemorrhage is variable, depending on its location. Even though sonography detected an intracranial anomaly in all cases, magnetic resonance imaging was necessary to establish the hemorrhagic nature of isolated subependymal and extradural hemorrhage. The similarity of histories involving minor maternal physical trauma in all cases, together with the absence of any known factor predisposing to fetal hemorrhage, may suggest that trauma is at least a contributing factor to the pathogenesis of fetal intracranial hemorrhage. PMID- 11778993 TI - Development of the human fetal corpus callosum: a high-resolution, cross sectional sonographic study. AB - OBJECTIVE: To establish reference ranges during human pregnancy for normal fetal corpus callosum dimensions. DESIGN: In a prospective, cross-sectional study of 258 fetuses between 16 and 37 weeks of gestation, measurements of the length, width, and thickness at the level of the anterior mid-body of the corpus callosum were performed, using high-resolution, transvaginal and transabdominal transducers. RESULTS: The mean length of the corpus callosum was 27.2 (standard deviation, 1.2; 95% confidence interval, 26.02-28.37) mm. Width and thickness of the corpus callosum were 5.6 (standard deviation, 1.6; 95% confidence interval, 5.41-5.82) mm and 1.9 (standard deviation, 0.7; 95% confidence interval, 1.87 2.06) mm, respectively. The size of the corpus callosum as a function of gestational age was expressed by regression equations: length (mm) = -20.40 + 1.92 x gestational age; width (mm) = -0.052 + 0.225 x gestational age; thickness (mm) = -0.174 + 0.085 x gestational age. The dimension-gestational age correlation coefficients were: r = 0.779 for length, r = 0.676 for width and r = 0.494 for thickness; these were statistically significant (P < 0.01). The maximum increase in thickness and width of the corpus callosum occurred between 19 and 21 weeks' gestation, while its length followed a constant growth rate. The normal mean length, width and thickness of the corpus callosum per week, and the 95% confidence limits, were defined. CONCLUSIONS: The present study offers normative measurements of the fetal corpus callosum and may facilitate a more objective diagnosis of its congenital abnormalities. PMID- 11778994 TI - First-trimester sonographic umbilical cord diameter and the growth of the human embryo. AB - OBJECTIVES: Experimental and clinical evidence have shown that the morphometry of the umbilical cord in the second half of gestation might be useful in predicting adverse perinatal outcome. The purposes of this study were to generate a nomogram for the umbilical cord diameter in the first trimester and, in an observational study, to investigate whether the sonographic measurement of the umbilical cord diameter early in gestation has the same clinical value as that late in gestation. METHODS: The sonographic umbilical cord diameter, crown-rump length and biparietal diameter were measured in 439 fetuses at between 8 and 15 weeks of gestation. The perinatal outcome was recorded for all patients. RESULTS: The umbilical cord diameter increased steadily from 8 to 15 weeks of gestation. A significant correlation was found between umbilical cord diameter and gestational age (r = 0.78; P < 0.001), umbilical cord diameter and crown-rump length (r = 0.75; P < 0.001) and umbilical cord diameter and biparietal diameter (r = 0.81; P < 0.001). No correlation was found between umbilical cord diameter values and either birth weight or placental weight. Among patients who had a miscarriage (n = 7) and pre-eclampsia (n = 8) the umbilical cord diameter was below 2 standard deviations from the mean in three cases (42.9%) and three cases (37.5%), respectively. CONCLUSION: The measurement of the umbilical cord diameter in the first trimester is correlated with the growth of the embryo and may be a marker for identifying a subset of fetuses at risk of spontaneous miscarriage and pre eclampsia. PMID- 11778995 TI - Effects of bleeding on uteroplacental, umbilicoplacental and yolk-sac hemodynamics in early pregnancy. AB - OBJECTIVE: To determine the influence of vaginal bleeding with or without a persisting subchorionic hematoma on uteroplacental, umbilicoplacental and yolk sac hemodynamics in early pregnancy. DESIGN: Twenty-six consecutive patients with vaginal bleeding entered this longitudinal study 1-3 days after the beginning of vaginal bleeding and were re-examined every 1-2 weeks. In three cases vaginal bleeding occurred at the 5th completed gestational week, in 13 at the 7th week, in nine at the 8th week and in one case at the 10th week. A subchorionic hematoma was identified in one case at the 5th week, in nine cases at the 7th week, in nine cases at the 8th week, and in seven cases at the 10th week. Four pregnancies ended in miscarriage. Blood velocity waveforms of uterine, arcuate, radial, spiral, umbilical, chorionic and yolk-sac arteries were obtained by transvaginal pulsed Doppler ultrasound and peak systolic velocities, time-averaged maximum velocities and pulsatility indices were calculated. The results were compared with our earlier observations in normal pregnancy obtained with a similar study protocol. RESULTS: At the 7th week, radial artery pulsatility-index values (mean (SD)) were higher in pregnancies with vaginal bleeding (1.84 (0.59); P = 0.04) and in pregnancies with a subchorionic hematoma (1.96 (0.63); P = 0.03) than in normal pregnancies (1.40 (0.46)). The pulsatility-index values of uterine, arcuate, spiral, umbilical and chorionic arteries did not differ between the groups. Vaginal bleeding with or without a subchorionic hematoma at the 8th week did not affect any of the measured parameters. Persistence of the subchorionic hematoma until the 10th week did not affect uterine, arcuate, radial, spiral, umbilical or chorionic artery hemodynamics. Yolk-sac hemodynamic parameters did not differ between the groups. CONCLUSIONS: Vaginal bleeding with or without a subchorionic hematoma is associated with increased radial artery impedance at the 7th week of pregnancy. Persistence of the subchorionic hematoma does not affect utero- and umbilicoplacental circulation. PMID- 11778996 TI - Comparison of 'pattern recognition' and logistic regression models for discrimination between benign and malignant pelvic masses: a prospective cross validation. AB - OBJECTIVES: To test prospectively the diagnostic performance of two logistic regression models for calculation of individual risk of malignancy in adnexal tumors (the 'Tailor model' and the 'Timmerman model'), and to compare them to that of 'pattern recognition' (subjective evaluation of the gray-scale ultrasound image and color Doppler ultrasound examination). DESIGN: Consecutive women with a pelvic mass judged clinically to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler examination. The same examination techniques and definitions as those used in the studies in which the logistic regression models had been created were used. The Tailor model was tested in 133 women (35 of whom hada malignancy) and the Timmerman model in 82 women (29 of whom had a malignancy). A subset of 79 women (28 of whom had a malignancy) was used to compare the performance of the Tailor model and the Timmerman model by calculating and comparing the areas under the receiver operating characteristics curves of the two models. Sensitivity and specificity with regard to malignancy were calculated for all three methods. RESULTS: Pattern recognition performed better than the two logistic regression models (sensitivity around 85%, specificity around 90%). Using a risk of malignancy of > 50% to indicate malignancy (as suggested in the original publications), the sensitivity of the Tailor model was 69% and the specificity 88% (n = 133). The corresponding values for the Timmerman model were 62% and 79% (n = 82). The receiver operating characteristics curves showed the two logistic regression models to have similar diagnostic properties (area under the curve, 0.87 vs. 0.84; P = 0.25; n = 79). The diagnostic performance of the mathematical models was much poorer in this study than in those in which the models had been created. CONCLUSION: The poor diagnostic performance of the mathematical models can probably be explained by subtle differences in definitions and examination technique and by differences between the original tumor populations and the study population. For mathematical models to be generally useful, they probably need to be created on the basis of a very large number of tumors, and the variables in the model must be unequivocally defined and the examination technique meticulously standardized. PMID- 11778997 TI - Vesicocentesis at 10-14 weeks of gestation for treatment of fetal megacystis. AB - This report of four cases shows that fetal vesicocentesis at 10-14 weeks of gestation is a useful treatment option in some cases with megacystis. Although megacystis at this gestation has been reported, there are few studies examining the role of early vesicocentesis. The natural history of the condition and outcome following treatment is reviewed with reference to the literature. PMID- 11778998 TI - A case of successful fetal therapy for congenital chylothorax by intrapleural injection of OK-432. AB - A 38-year-old multiparous woman was referred at 19 weeks' gestation because of hydrops fetalis. Ultrasonic examination revealed severe pleural effusion, ascites and skin edema. Detailed examination of the amniotic fluid, fetal blood and intrathoracic fluid led to a diagnosis of congenital fetal chylothorax. Repeated thoracocenteses were not effective in improving the hydrops fetalis. We introduced fetal treatment for the pleural effusion by an intrapleural injection of OK-432 at 23, 24 and 25 weeks' gestation. The pleural effusion was reduced by adhesion of the intrathoracic space and resulted in the delivery of a neonate who was healthy except for right renal dysfunction. Pulmonary hypoplasia was successfully prevented by OK-432. PMID- 11778999 TI - A new fetal therapy for chylothorax: pleurodesis with OK-432. AB - We present a case of pleurodesis by intrapleural injection of OK-432 for the treatment of fetal chylothorax at an early gestational age. OK-432 injection achieved rapid and effective control of pleural effusion with no adverse effects. PMID- 11779000 TI - Early prenatal sonographic diagnosis and follow-up of Jeune syndrome. AB - Jeune syndrome or asphyxiating thoracic dysplasia is an autosomal recessive osteochondrodysplasia. It is one of the six short-rib (polydactyly) syndromes. The disease has a wide spectrum of manifestations, ranging from a latent to a mild or lethal condition. We describe the prenatal sonographic diagnosis of Jeune syndrome at 14 weeks of gestation in a fetus at risk for this condition, and the development of the syndrome throughout the pregnancy. PMID- 11779001 TI - Ultrasound diagnosis of postpartum ovarian vein thrombosis: case report. AB - Postpartum ultrasound investigation of a woman with unremitting fever and right flank pain after Cesarean section revealed an extensive thrombosis of the right ovarian vein which extended into the inferior vena cava. Computed tomography was required to substantiate the diagnosis. Medical treatment with intravenous urokinase and heparin and antibiotics was successfully performed. During the postpartum period, the possibility of ovarian vein thrombosis should be considered in febrile patients with abdominal pain who are not responding to antibiotics, and imaging studies such as ultrasound and computed tomography should be performed early for prompt diagnosis and therapy. PMID- 11779002 TI - Clinical implications of sonographic detection of uterine anomalies for reproductive outcome. AB - The purpose of this review article was to analyze the literature on the prevalence, diagnosis and treatment of the congenital uterine anomalies and to discuss current dilemmas on their influence on reproductive outcome. Congenital uterine anomalies are commonly associated with repeated pregnancy failure, in particular an increased risk of first- and second-trimester miscarriages and preterm delivery. Recent reports on two-dimensional and three-dimensional transvaginal ultrasound and saline contrast sonohysterography appear promising for diagnosis and classification of congenital uterine anomalies. The ability to visualize both the uterine cavity and the fundal uterine contour on a three dimensional scan facilitates the diagnosis of uterine anomalies and enables differentiation between septate and bicornuate uteri. Color Doppler ultrasound allows visualization of intraseptal vascularity and may help in distinguishing the avascular from the vascular septum. Less connective tissue in the septum may result in poor decidualization and placentation, while an increased amount of muscle tissue in the septum can cause miscarriage by the production of local uncoordinated myometrial contractility. Hysteroscopic septum excision is an effective procedure which improves live-birth rates. Because of its simplicity, minimal invasiveness, low morbidity and low cost, a more liberal approach to the treatment of uterine anomalies is being advocated. PMID- 11779003 TI - Resolution of fetal bilateral chylothorax and ascites after two unilateral thoracocenteses. PMID- 11779004 TI - Fetal phallus 'erection' interfering with the sonographic determination of fetal gender in the first trimester. PMID- 11779005 TI - Fetal penile erection. PMID- 11779006 TI - Start of the art of the heart. PMID- 11779007 TI - Picture of the month. Visualization of fetal arterial and venous coronary blood flow. PMID- 11779008 TI - Square stent: a new self-expandable endoluminal device and its applications. AB - The square stent is a new, simply constructed, self-expanding device that has recently been described. Compared with other stents, the square stent has a minimal amount of metal and thus requires a smaller-diameter catheter for introduction. Despite the small amount of metal present, the square stent has adequate expansile force. We have been evaluating the square stent for various interventional applications. In addition to the basic square stent, combinations of square stents and coverings for square stents were developed and evaluated to expand its uses and indications. One of the coverings tested is a new biomaterial: small intestinal submucosa (SIS). This paper will discuss the various applications of the square stent, which include a retrievable inferior vena cava filter, vascular occluder, graft adapter, and venous and aortic valves. In addition, we will review the important properties of SIS as a covering for the square stent. PMID- 11779009 TI - rt-PA thrombolysis in acute thromboembolic upper-extremity arterial occlusion. AB - PURPOSE: Retrospective analysis of the results of rt-PA thrombolysis in the treatment of acute thromboembolic occlusion of the upper limb. METHODS: Of 55 patients with demonstrated acute embolic arterial occlusion, rt-PA thrombolysis was performed on 40 occlusions in 38 patients (23 women with a mean age of 62 years, range 32-85 years; 15 men with a mean age of 65 years, range 32-92 years) according to the following design: 6 mg rt-PA/hr for 30 min, 3 mg rt-PA/hr for the next 30 min, 1 mg rt-PA/hr for 7 hr, and 0.4 mg rt-PA/hr until the end of lysis. Onset of symptoms varied from 1 to 14 days. Included were three isolated upper-arm occlusions, nine combined brachial and forearm occlusions, and 28 forearm and hand artery occlusions. RESULTS: The overall success rate was 55%. The lysis results for isolated upper arm, combined brachial and forearm occlusions, and forearm and hand artery occlusions were 100%, 66%, and 46%, respectively. In eight patients surgical embolectomy had to be performed after failed thrombolysis. No amputation was required in the follow-up period. No lethal complications occurred. CONCLUSIONS: Interventional rt-PA treatment of proximal upper-extremity arterial occlusions may be performed with comparable success rates to surgical embolectomy and without severe complications. For distal occlusions the results are inferior to the success rates obtained with surgery. PMID- 11779010 TI - Complications of percutaneous nephrostomy, percutaneous insertion of ureteral endoprosthesis, and replacement procedures. AB - PURPOSE: The aim of the present study was to record and identify the frequency of complications following percutaneous nephrostomy, replacement of nephrostomy drains and percutaneous insertion of ureteral endoprostheses. METHODS: During a 10-year period 341 patients were referred to our department with indications for percutaneous nephrostomy and/or percutaneous insertion of a ureteral endoprosthesis, and a total of 1036 interventional procedures were performed (nephrostomy, catheter change, stenting). RESULTS: There were three major complications (0.29%): two patients died during the first 30 days after the procedure, due to aggravation of their condition caused by the procedure, and one patient had retroperitoneal bleeding requiring surgery. There were 76 complications of intermediate severity (7.33%): catheter or stent displacement (n = 37, 3.57%) catheter occlusion (n = 18, 1.73%), hematuria (n = 12, 1.16%), and urinary tract infection (n = 9, 0.87%). The 55 minor complications (5.3%) comprised inflammation of the skin at the site of insertion of the percutaneous catheter. CONCLUSION: The small number of complications observed during acts of interventional uroradiology prove transcutaneous manipulations to be safe medical procedures. PMID- 11779011 TI - The role of duplex scanning in the selection of patients with critical lower-limb ischemia for infrainguinal percutaneous transluminal angioplasty. AB - PURPOSE: To investigate the role of duplex scanning in the selection of patients with critical lower-limb ischemia (CLI) for infrainguinal percutaneous transluminal angioplasty (PTA). METHODS: One hundred and sixty-two limbs with CLI (150 patients) that underwent duplex scanning within 3 months prior to conventional diagnostic angiography (n = 88) or infrainguinal PTA (n = 74) were retrospectively studied. The findings obtained from duplex scanning and angiography were analyzed in a masked fashion by two different investigators. RESULTS: The accuracy, sensitivity, specificity, and negative and positive predictive values of duplex scanning in the selection of patients for infrainguinal PTA were 86%, 84%, 89%, 86%, and 87% respectively. Forty-two procedures (57%) were performed at multiple arterial segments. The accuracy of duplex scanning in the selection of femoropopliteal and crural lesions for PTA was over 85%. However, the sensitivity of duplex scanning in the selection of popliteal and crural lesions for PTA was 49% and 38% respectively, compared with 80% for superior femoral artery lesions. In 39% of patients who were correctly selected for PTA, duplex scanning misdiagnosed one of the multiple lesions treated by PTA. CONCLUSION: Duplex scanning can safely be used for the selection of patients for infrainguinal PTA. The sensitivity of duplex scanning in the selection of lesions for PTA was less satisfactory in the popliteal and crural arteries compared with the femoropopliteal arteries. PMID- 11779012 TI - Can MR measurement of renal artery flow and renal volume predict the outcome of percutaneous transluminal renal angioplasty? AB - PURPOSE: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA. METHODS: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath hold, cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm3). RESULTS: Clinical success was observed in patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm3 predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm3 identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001). CONCLUSION: A combination of cine phase-contrast MR renal flow and parenchymal volume measurements enables identification of patients benefiting from PTRA with a high sensitivity and NPV, but only moderate specificity and PPV. PMID- 11779013 TI - A comparative study of CT fluoroscopy combined with fluoroscopy versus fluoroscopy alone for percutaneous transhepatic biliary drainage. AB - PURPOSE: We compared CT fluoroscopy (CTF) for the initial puncture of bile ducts with conventional fluoroscopic guidance in patients with malignant jaundice in whom percutaneous transhepatic biliary drainage (PTBD) was planned. METHODS: Forty consecutive patients were randomized to two study groups: group A underwent PTBD under CTF and fluoroscopic guidance, group B underwent PTBD under fluoroscopic guidance alone. CTF-guided PTBD was performed using a combination of a helical CT scanner of the latest generation and a mobile C-arm; conventional PTBD was performed under fluoroscopic guidance in the angiographic unit. End points of the study were the success (a puncture that enabled safe placement of a guidewire in a suitable bile duct) and the complication rate (hemobilia, bile fistula, biliary peritonitis), the number of punctures required, the time needed for successful puncture of a suitable bile duct, and the patient's radiation exposure. RESULTS: CTF-guided puncture of peripheral bile ducts suitable for PTBD was successful at the first attempt in 16 cases, under conventional fluoroscopic guidance, in only two cases. We found a significantly different number of punctures (1.2 in group A vs 2.9 in group B), a significantly shorter time for puncture in group A (mean 39 sec), but also a significantly higher skin exposure dosage in group A (mean 49.5 mSv surface dosage). There was no significant difference regarding the total procedure time. Only one complication occurred in group B (portobiliary fistula). CONCLUSION: CTF-guided initial puncture of bile ducts allowed a significantly reduced number of punctures and puncture times compared with puncture under conventional fluoroscopic guidance for placement of percutaneous transhepatic biliary drainage catheters. PMID- 11779014 TI - Nitinol stents for palliative treatment of malignant obstructive jaundice: should we stent the sphincter of Oddi in every case? AB - PURPOSE: To evaluate the necessity of metallic stenting of the sphincter of Oddi in malignant obstructive jaundice when the tumor is more than 2 cm from the papilla of Vater. METHODS: Sixty-seven self-expandable biliary stents were used in 60 patients with extrahepatic lesions of the common hepatic or common bile duct and with the distal margin of the tumor located more than 2 cm from the papilla of Vater. Stents were placed above the papilla in 30 cases (group A) and in another 30 with their distal part protruding into the duodenum (group B). RESULTS: The 30-day mortality was 15%, due to the underlying disease. The stent occlusion rate was 17% after a mean period of 4.3 months. No major complications were noted. Average survival was 132 days for group A and 140 days for group B. In group A, 19 patients survived < or = 90 days and in eight of these, cholangitis occurred at least once. Of 11 patients in group A with survival > 90 days, only two developed cholangitis. In group B, 13 patients who survived < or = 90 days had no episodes of cholangitis and in 17 with survival > 90 days, cholangitis occurred in three. There is a statistically significant difference (p < 0.05) regarding the incidence of cholangitis in favor of group A. CONCLUSIONS: In patients with extrahepatic lesions more than 2 cm from the papilla and with a relative poor prognosis (< or = 3 months), due to more advanced disease or to a worse general condition, the sphincter of Oddi should also be stented in order to reduce the postprocedural morbidity. PMID- 11779015 TI - Clinical results of cerebral protection with a filter device during stent implantation of the carotid artery. AB - PURPOSE: To assess the technical feasibility and the clinical results of cerebral protection with the Angioguard emboli-capture guidewire system during carotid artery stenting (CAS) for high-grade stenoses. METHODS: In 20 patients 20 stenoses of the internal carotid artery were treated with stent implantation. In all patients diffusion-weighted (DW) magnetic resonance imaging (MRI) of the brain was performed before and 24 hr after the procedure. RESULTS: The filter device was effectively employed during all steps of the procedure in 16 of 20 patients, in two only postdilation could be protected, and in two no protection was possible. After three of the 20 procedures new ipsilateral cerebral lesions were visualized by DW-MRI. No new permanent neurologic deficits occurred. CONCLUSION: Cerebral protection with the filter device is technically feasible in most cases. DW-MRI demonstrated new cerebral lesions indicating the occurrence of cerebral microemboli during the protected procedures. Further investigations are necessary to determine whether the use of the cerebral protection device will improve the results of CAS. PMID- 11779016 TI - Renal failure secondary to thrombotic complications of suprarenal inferior vena cava filter in cancer patients. AB - PURPOSE: To evaluate renal function before and after suprarenal inferior vena cava (IVC) filter placement. METHODS: We describe, in a personal series of 13 consecutive cases (all of them stage IV cancer patients, one LGM filter, one Antheor filter, 11 Greenfield filters) in our institution, two cases of fatal renal vein thrombosis after placement of a suprarenal filter. Evaluation of renal function was based on serum urea (in mmol/L; normal 3.30-6.60), serum creatinine (in micromol/L; normal <115.1), and calculation of serum creatinine clearance. RESULTS AND CONCLUSION: This study suggests that in advanced-stage cancer patients who have a single functional kidney, renal functional insufficiency, or previous renal vein thrombosis, IVC filter placement above the renal veins may not be appropriate. Suprarenal filter placement should be performed only after analysis of predicted survival, after detailed discussions with the patient, and most importantly after renal function evaluation. PMID- 11779017 TI - Nonbiodegradable expanded polytetrafluoroethylene-covered stent implantation in porcine peripheral arteries: histologic evaluation of vascular wall response compared with uncoated stents. AB - PURPOSE: To test the vascular wall response to an expanded polytetrafluoroethylene-covered stent, compared with conventional stenting, up to 6 months after deployment in the vascular district of a swine model. METHODS: Fourteen minipigs underwent implantation of expanded polytetrafluoroethylene covered stents (CS) and bare stents (BS) in five peripheral arteries. Animals were killed at different time points (from 1 to 180 days). Histopathologic assessment by morphologic and morphometric analysis and by scanning electron microscopy (SEM) were used to assess the incorporation characteristics and re endothelialization extent of the two types of stents. RESULTS: A total of 70 stents (14 CS and 14 BS in the renal arteries; 28 CS in the iliac arteries, and 14 CS in the aorta) were implanted. Microscopic examination confirmed the absence of occlusive thrombi in both the CS and BS groups. Microthrombi were observed in 10 of 13 CS (77% of cases) and in four of four BS (100% of cases, p < 0.05). Inflammation was mild in 69% of segments in which a CS was implanted and in 74% of segments in which a BS was implanted (p = NS), while a severe inflammatory reaction was observed in 6% of CS segments and in 8% of BS segments (p = NS). No differences were detected at the long-term analysis between neointimal thickness in CS compared with BS segments (0.46 +/- 0.18 mm vs 0.42 +/- 0.26 mm at 90 days and 0.36 +/- 0.08 mm vs 0.35 +/- 0.04 mm at 180 days; p = NS, respectively). At SEM analysis, re-endothelization was evident 15 days after the implant in both CS and BS starting from the stent edges. CONCLUSION: CS implantation did not elicit a more severe thrombotic deposition compared with that of BS. A similar inflammatory reaction of the arterial wall was present in the two stent groups 3 and 6 months following the implant. In addition, CS implantation did not stimulate excessive neointimal formation when compared with BS. PMID- 11779018 TI - Right posterior-superior subsegmental hepatic artery originating from the right inferior adrenal artery. PMID- 11779019 TI - Temporary percutaneous aortic balloon occlusion to enhance fluid resuscitation prior to definitive embolization of posttraumatic liver hemorrhage. AB - We successfully stabilized severe hemorrhagic shock following traumatic liver injury by percutaneous transcarotid supraceliac aortic occlusion with a 5 Fr balloon catheter. Then we were able to perform transfemoral embolization therapy of the hepatic arterial bleeding source. Transient aortic occlusion using a balloon catheter appears to be a useful adjunct in select cases where stabilization of the patient is necessary to allow successful selective embolization of the bleeding source. PMID- 11779020 TI - A system for computer-assisted design of stent-grafts for aortic aneurysms using 3-D morphological models. AB - A three-dimensional model was constructed from helical CT images for abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). A stent-graft was designed and positioned endoluminally on the computer. One hundred and nine stent grafts for 101 patients were designed by this method and deployed well in all patients. The design time was reduced from 4 to 0.5 hr. PMID- 11779021 TI - Repair of infrapopliteal postembolectomy complications with variant embolization techniques. AB - Infrapopliteal pseudoaneurysms and arteriovenous fistulae are known complications of Fogarty balloon embolectomy. Management of these complications in two patients with associated critical foot ischemia by modified interventional embolization techniques is described. PMID- 11779022 TI - Pseudoaneurysm of the internal carotid artery: treatment with a covered stent. AB - Dissection of the cervical segment of the internal carotid artery may occur spontaneously or after trauma. We report the management of a 53-year-old right handed man with progressive dizziness and neck pain 6 weeks after a motor vehicle collision. The clinical and neurologic examinations were normal. The CT scan led to the diagnosis of a pseudoaneurysm of the right internal carotid artery near the skull base. We successfully treated this post-traumatic lesion with a covered stent. The patient underwent the endovascular procedure under general anesthesia and transcranial Doppler monitoring. No neurologic event was observed. Obliteration of the pseudoaneurysm with preservation of the carotid artery was achieved. The patient was discharged from the hospital 72 hr later with no complications. Clinical and imaging follow-up at 6 months was unremarkable. PMID- 11779023 TI - Delayed spontaneous superior vena cava perforation associated with a SVC wallstent. AB - A patient was referred for superior vena cava (SVC) stenting prior to surgical biopsy of a mediastinal mass. A technically satisfactory insertion was followed 6 months later by cardiac tamponade with two legs of the Wallstent having perforated the wall of the SVC. PMID- 11779024 TI - Re: CT-guided microwave coagulation therapy with needle guidance for hepatocellular carcinoma. PMID- 11779025 TI - Potentiation of GABA(A) receptor agonists by GABA uptake inhibitors in the rat ventral midbrain. AB - Whole-cell patch recordings were made from dopamine-containing neurons in the ventral tegmental area (VTA) and substantia nigra zona compacta (SNC). Isoguvacine evoked an outward current (at -60 mV) in a concentration-dependent manner with an EC50 of 62+/-8 microM. The gamma-aminobutyric acid (GABA) uptake inhibitor 1-(2(((diphenylmethylene)imino)oxy)ethyl)-1,2,5,6-tetrahydro-3 pyridinecarboxylic acid hydrochloride (NO 711) (3 microM) shifted the isoguvacine concentration-response curve to the left, with a new EC50 of 22+/-4 microM. L Arginine (3 mM) also shifted the isoguvacine concentration-response curve to the left, with a new EC50 of 29+/-5 microM. L-Arginine (3 mM) increased the currents evoked by GABA (100 microM) and muscimol (1 microM) by 208% and 261%, respectively. The GABA uptake inhibitor 4,5,6,7,-tetrahydroisoxazolo[4,5-c] pyridin-3-ol hydrobromide (THPO) (300 microM) not only mimicked but also occluded the ability of L-arginine (3 mM) to potentiate currents evoked by isoguvacine. Equimolar replacement of Na+ with choline increased GABA-evoked currents, suggesting that a low Na+ concentration has an inhibitory effect on GABA transport. Low Na+ concentration (25 mM) inhibited isoguvacine currents but still occluded the potentiating effects of L-arginine. We conclude that GABA uptake inhibitors potentiate the actions of the GABA(A) receptor agonists, isoguvacine and muscimol, probably because they are effective substrates for GABA transporters in the ventral midbrain. PMID- 11779026 TI - Impaired neurogenic and endothelium-dependent relaxant responses of corpus cavernosum smooth muscle from hyperthyroid rabbits. AB - We investigated the effect of hyperthyroidism on the responsiveness of the rabbit corpus cavernosum smooth muscle. In male albino rabbits, hyperthyroidism was established by oral feeding of L-thyroxine at increasing dosages (150-450 microg/kg) over an 8-week period. This treatment produced a stable hyperthyroid state as indicated by the increased serum T4 levels. The reactivity of corpus cavernosum tissue from hyperthyroid animals and euthyroid control animals was studied in organ chambers. Hyperthyroidism caused impaired neurogenic and endothelium-dependent relaxant responses with decreased Emax and pD2 values. However, hyperthyroidism had no effect on both phenylephrine- and KCl-induced contractile responses and sodium nitroprusside- and papaverine-induced endothelium-independent relaxant responses, and there was no change in agonist potency. These data indicate that hyperthyroidism may impair both neurogenic and endothelium-dependent relaxation of corporal smooth muscle, and may contribute to the etiology of impotence. PMID- 11779027 TI - Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs. AB - The present study was performed to determine the tubular sites of nitrite and nitrate (NO) reabsorption and the effects of furosemide on the renal handling of NOx in anesthetized dogs, using renal clearance and stop-flow methods. Furosemide (2 mg/kg, i.v.) increased the urinary excretion rates of Na+ (U(Na+)V) and NOx (U(NOx)V) with a reduction of tubular reabsorption rates of Na+ and NOx. During inhibition of renal nitric oxide (NO) synthesis by an intrarenal infusion of L nitro arginine (30 microg/kg-min), furosemide also increased U(NOx)V and decreased tubular reabsorption rate of NOx from 96.5+/-0.8% to 86.6+/-1.7%. An intravenous infusion of 10% mannitol (0.5 ml/kg-min) also increased both U(Na+)V and U(NOx)V. In addition, after furosemide administration or mannitol infusion. U(NOx)V was correlated with U(Na+)V. In stop-flow experiments, the distal dip in NOx curve was observed and the site of the dip in NOx curve was identical to that of Na+ curve. Furosemide shifted upward the U/P(Na+)/U/P(Cr) and U/P(NOx)/U/P(Cr) at the distal dip, indicating inhibition of Na+ and NOx reabsorption at distal tubules. These results indicate that more than 96% of the filtered NOx is reabsorbed in the renal tubules, and that the tubular handling of NOx is very close to that of Na+. In addition, the stop-flow experiments demonstrate that furosemide inhibited the reabsorption of NOx as well as Na+ at the distal tubule. PMID- 11779028 TI - Differential uptake of grepafloxacin by human circulating blood neutrophils and those exudated into tissues. AB - The uptake of the antimicrobial quinolone agent, grepafloxacin, both by human circulating blood neutrophils and by those exudated into tissues, was evaluated in vitro by comparing the intracellular drug concentrations. In circulating blood neutrophils, the uptake of grepafloxacin was rapid and saturable at 37 degrees C. The uptake of grepafloxacin into circulating blood neutrophils was reduced by lowering the environmental temperature or by the presence of metabolic inhibitors, suggesting the involvement of an active transport mechanism. Furthermore, the uptake of grepafloxacin by tissue (salivary) neutrophils was also partially temperature-dependent and was significantly greater than that by circulating blood neutrophils, i.e. exudation of neutrophils into tissue results in a markedly enhanced transport mechanism for grepafloxacin. This phenomenon may be related to the higher defense activity against infection seen in exudated tissue neutrophils. PMID- 11779029 TI - Antisense oligodeoxynucleotides to mu- and delta-opioid receptor mRNA block the enhanced effects of opioids during intestinal inflammation. AB - Intestinal inflammation enhances the inhibitory effects of mu- and delta-opioids in the gut, possibly related to an increased receptor expression. We evaluated the effects of opioids after intraperitoneal administration of antisense oligodeoxynucleotides to mu- and/or delta-opioid receptor mRNA. Inflammation was induced in mice by intragastric administration of croton oil; gastrointestinal transit was assessed with charcoal and permeability with [51Cr]etylenediaminetetraacetate ([51Cr]EDTA). Baseline values were unaltered after antisense oligodeoxynucleotides. In controls, antisense oligodeoxynucleotides to mu-opioid receptor mRNA decreased the antitransit effects of morphine (27%) and [N-MePhe3D-Pro4]morphiceptin (PL017) (26%), and the reduction was significantly greater during inflammation (50% and 47%). A similar effect was observed on permeability (control: 41-21% decrease; inflamed: 66-45%). In both assays, antisense oligodeoxynucleotides to delta-opioid receptor mRNA also reduced the effects of [D-Pen2,5]enkephalin (DPDPE) in a higher percentage during inflammation (43-32% controls, 60-49% inflamed). We show that antisense oligodeoxynucleotides to mu- and/or delta-opioid receptor mRNA are efficiently blocking the intestinal effects of opioids during inflammation, suggesting that an increased transcription of these receptors in the gut mediates the enhanced effects of opioids during inflammation. PMID- 11779030 TI - Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity. AB - One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3 hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by oleanonic acid with an IC50 of 17 microM. Negligible differences were observed in the response of both triterpenes to DPP, bradykinin, and phospholipase A2, while oleanonic acid was more active on the dermatitis by TPA and on the in vitro leukotriene formation. In conclusion, the presence of a ketone at C-3 implies an increase in the inhibitory effects on models related to 5-lipoxygenase activity and on associated in vivo inflammatory processes. PMID- 11779031 TI - Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat. AB - The effects of pinealectomy and exogenous melatonin (N-acetyl-5 methoxytryptamine) on serum leptin levels were investigated in rats. Exogenous administration of melatonin to intact rats resulted in significant decreases in serum leptin levels (P < 0.05) compared to those of the intact control group. Serum leptin levels were significantly elevated in the pinealectomised rats in comparison to the sham-pinealectomised animals (P < 0.001) and were significantly suppressed by exogenous administration of melatonin compared to those of non treated pinealectomised rats (P < 0.001). Hormone concentrations in the melatonin treated pinealectomised group were found to be similar to those seen in the sham pinealectomised group. These results suggest that pineal gland has an effect on leptin release. PMID- 11779032 TI - Hibernation-induction peptide and cell death: [D-Ala2,D-Leu5]enkephalin blocks Bax-related apoptotic processes. AB - The psychostimulant methamphetamine, both in vivo and in vitro, caused a mitochondrial cytochrome c release, the translocation of Bax from cytosol into mitochondrion, and the oligomerization of Bax. These effects by methamphetamine were blocked by a neuroprotective and hibernation-induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE). These results suggest that methamphetamine causes apoptosis by affecting the dynamics of Bax and that the neuroprotective property of DADLE may be due partly to its ability to potently block Bax-related apoptotic processes. PMID- 11779033 TI - Growth inhibitory activity of indapamide on vascular smooth muscle cells. AB - Abnormal vascular smooth muscle cell proliferation has a fundamental role in the pathogenesis of vascular diseases. Indapamide is an oral diuretic antihypertensive drug effective for patients with mild or moderate essential hypertension. We now investigated the effects of indapamide on the growth of aortic vascular smooth muscle cells (A10 cell line). Indapamide inhibited cell proliferation as measured by the tetrazolium salt XTT (sodium 3'-[1-(phenylamino carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate) test. The increase in cell number was significantly reduced in the presence of indapamide 10(-6) and 5 x 10(-4) M (P < 0.05 n = 3 and P < 0.01, n = 3, respectively). Serum-induced DNA synthesis, determined as the incorporation of 5 bromo-2'-deoxyuridine (BrdU), was concentration-dependently inhibited by indapamide. BrdU incorporation was 47.2+/-1.6% (10% foetal calf serum). Indapamide treatment markedly prevented BrdU incorporation (37.2+/-2.1%, 29.2+/ 4.8%, 15.0+/-1.8%, 8.7+/-2.1%) indapamide 10(-6), 10(-5), 5 x 10(-5) and 5 x 10( 4) M, respectively. Cell-cycle progression was also evaluated. Flow cytometry analysis of DNA content in synchronised cells revealed blocking of the serum inducible cell-cycle progression by indapamide. This inhibition was abolished when the drug was added 2 h after serum repletion, indicating that indapamide must act at the early events of a cell cycle to be fully effective against DNA synthesis. In addition, serum-induced intracellular Ca2+ movements and also p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation were studied in the presence or absence of indapamide. Indapamide 10(-5) and 5 x 10(-5) M decreased significantly cytosolic free calcium, and the p44/p42 mitogen-activated protein kinase phosphorylation (5 x 10(-5) M) stimulated by 10% foetal calf serum. In accordance with this finding, indapamide (5 x 10(-4) M) caused a 95% to 99% decrease in the early elevation of c-fos expression as evaluated by northern blot analysis of mRNA induced after serum addition. In conclusion, our results indicate that indapamide reduces vascular smooth muscle cell proliferation by a mechanism which involves a decrease in the intracellular Ca2+ movements that might link with the mitogen-activated protein kinase (MAPK) pathway, altering cell-cycle progression. PMID- 11779034 TI - Characterization of opiates, neuroleptics, and synthetic analogs at ORL1 and opioid receptors. AB - Nociceptin/orphanin FQ (N/OFQ) was recently identified as the endogenous ligand for the opioid-receptor like (ORL1) receptor. Although the ORL1 receptor shows sequence homology with the opioid receptors, the nociceptin/ORL1 ligand-receptor system has very distinct pharmacological actions compared to the opioid receptor system. Recently, several small-molecule ORLI receptor ligands were reported by pharmaceutical companies. Most of these ligands had close structural similarities with known neuroleptics and opiates. In this study, we screened several available neuroleptics and opiates for their binding affinity and functional activity at ORL1 and the opioid receptors. We also synthesized several analogs of known opiates with modified piperidine N-substituents in order to characterize the ORL1 receptor ligand binding pocket. Substitution with the large, lipophilic cyclooctylmethyl moiety increased ORL1 receptor affinity and decreased mu receptor affinity and efficacy in the fentanyl series of ligands but had a different effect in the oripavine class of opiate ligands. Our results indicate that opiates and neuroleptics may be good starting points for ORL1 receptor ligand design, and the selectivity may be modulated by appropriate structural modifications. PMID- 11779035 TI - The iron chelator pyridoxal isonicotinoyl hydrazone inhibits mitochondrial lipid peroxidation induced by Fe(II)-citrate. AB - Pyridoxal isonicotinoyl hydrazone (PIH) is able to prevent iron-mediated hydroxyl radical formation by means of iron chelation and inhibition of redox cycling of the metal. In this study, we investigated the effect of PIH on Fe(II)-citrate mediated lipid peroxidation and damage to isolated rat liver mitochondria. Lipid peroxidation was quantified by the production of thiobarbituric acid-reactive substances (TBARS) and by antimycin A-insensitive oxygen consumption. PIH at 300 microM induced full protection against 50 microM Fe(II)-citrate-induced loss of mitochondrial transmembrane potential (deltapsi) and mitochondrial swelling. In addition, PIH prevented the Fe(II)-citrate-dependent formation of TBARS and antimycin A-insensitive oxygen consumption. The antioxidant effectiveness of 100 microM PIH (on TBARS formation and mitochondrial swelling) was greater in the presence of 20 or 50 microM Fe(II)-citrate than in the presence of 100 microM Fe(II)-citrate, suggesting that the mechanism of PIH antioxidant action is linked with its Fe(II) chelating property. Finally, PIH increased the rate of Fe(II) autoxidation by sequestering iron from the Fe(II)-citrate complex, forming a Fe(III)-PIH, complex that does not participate in Fenton-type reactions and lipid peroxidation. These results are of pharmacological relevance since PIH is a potential candidate for chelation therapy in diseases related to abnormal intracellular iron distribution and/or iron overload. PMID- 11779036 TI - WIN 17317-3 blocks Ca2+-activated K+ channels and enhances motility of guinea-pig detrusor muscle. AB - Patch-clamp experiments in both clonal GH3 cells and guinea-pig bladder myocytes reveal that 1-benzyl-7-chloro-4-(n-pentylimino)-1,4-dihydroquinoline hydrochloride (WIN 17317-3), a potent blocker of Kv1.3 channels and potential immunomodulator, reduces, in a reversible manner and at low micromolar concentrations, K+ currents through Ca2+-activated high conductance K+ channels (BK channels). Blockade of BK channels is thought to account for the stimulatory effect of WIN 17317-3 on the contractility of guinea-pig bladder. This effect is not modified by tetrodotoxin (1 microM), but is abolished by nifedipine (0.1 microM). In conclusion. WIN 17317-3 lacks selectivity for the Kv1.3 channels, its postulated target for immunosuppression. PMID- 11779037 TI - Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. AB - The cannabinoid CB1 receptor has been shown to be the primary site of action for cannabinoid-induced effects on the central nervous system. Activation of this receptor has proven to dampen neurotransmission and produce an overall reduction in neuronal excitability. Cannabinoid compounds like delta9-tetrahydrocannabinol and cannabidiol have been shown to be anticonvulsant in maximal electroshock, a model of partial seizure with secondary generalization. However, until now, it was unknown if these anticonvulsant effects are mediated by the cannabinoid CB1 receptor. Likewise, (R)-(+)-[2,3-Dihydro-5-methyl-3-(4 morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN 55,212-2), a cannabimimetic compound that has been shown to decrease hyperexcitability in cell culture models via the cannabinoid CB1 receptor, has never been evaluated for anticonvulsant activity in an animal seizure model. We first show that the cannabinoid compounds delta9-tetrahydrocannabinol (ED50 = 42 mg/kg), cannabidiol (ED50 = 80 mg/kg), and WIN 55,212-2 (ED50 = 47 mg/kg) are anticonvulsant in maximal electroshock. We further establish, using the cannabinoid CB1 receptor specific antagonist N-(piperidin-1-yl-5-(4-chlorophenyl) 1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) (AD50 = 2.5 mg/kg), that the anticonvulsant effects of delta9 tetrahydrocannabinol and WIN 55,212-2 are cannabinoid CB1 receptor-mediated while the anticonvulsant activity of cannabidiol is not. This study establishes a role for the cannabinoid CB1 receptor in modulating seizure activity in a whole animal model. PMID- 11779038 TI - The effect of nitric oxide on acetylcholine release in the rabbit bladder. AB - We evaluated the effects of nitric oxide (NO) on acetylcholine release and the contractile response induced by electrical field stimulation in rabbit bladder smooth muscles using a muscle bath and high performance liquid chromatography coupled with microdialysis. Electrical field stimulation (supramaximum voltage, pulse duration 0.5 ms, frequency 5 and 20 Hz) was applied to a smooth muscle strip isolated from rabbit bladder. With low-frequency (5 Hz) stimulation, pretreatment with Nomega-nitro-L-arginine (L-NNA) (100 microM) significantly increased electrical field stimulation-induced acetylcholine release and contractile response, which were reduced by the addition of L-arginine. Pretreatment with sodium nitroprusside in the absence or presence of L-NNA significantly decreased electrical field stimulation-induced acetylcholine release and contractile response. In contrast, with high frequency (20 Hz) stimulation, pretreatment with L-NNA and sodium nitroprusside had no significant effect on either contractile response or acetylcholine release. Pretreatment with sodium nitroprusside caused no significant changes in carbachol and ATP-induced contractile responses. Sodium nitroprusside and L-NNA had no significant effects on the atropine-resistant part of the contraction induced by electrical field stimulation in rabbit bladder smooth muscles. The results suggest that there is a NO-mediated mechanism inhibiting acetylcholine release from cholinergic nerve endings in rabbit bladder, which may contribute to bladder function. PMID- 11779039 TI - Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum. AB - Nornicotine, a major tobacco alkaloid and nicotine metabolite, accumulates in rat brain in pharmacologically relevant concentrations following repeated nicotine administration. Nornicotine-evoked striatal dopamine release is Ca2+-dependent, stereoselective and sensitive to nicotinic receptor antagonists, indicating nicotinic receptor-mediation. The present study determined if S-(-)-nornicotine desensitizes nicotinic receptors and if cross-desensitization to S-(-)-nicotine occurs. S-(-)-Nicotine (10 and 100 nM) diminished [3H]overflow from [3H]dopamine preloaded rat striatal slices following subsequent superfusion with 10 microM S-( )-nicotine (46% and 74%, respectively) or 10 microM S-(-)-nornicotine (59% and 81%, respectively). S-(-)-Nornicotine (1 and 10 microM) diminished the response to subsequent superfusion with 10 microM S-(-)-nornicotine (85% and 97%, respectively) or 10 microM S-(-)-nicotine (82% and 88%, respectively). Thus, similar to S-(-)-nicotine, S-(-)-nornicotine desensitizes nicotinic receptors. but with approximately 12-fold lower potency. Cross-desensitization suggests involvement of common nicotinic receptor subtypes. Therefore, S-(-)-nicotine metabolites, such as nornicotine, have neuropharmacologically relevant effects. PMID- 11779040 TI - Effect of 5-HT1A and 5-HT2A/2C receptor modulation on neuroleptic-induced vacuous chewing movements. AB - Tardive dyskinesia is a serious motor side effect of chronic neuroleptic therapy. Chronic treatment or rats with neuroleptics leads to the development of abnormal oral movements called vacuous chewing movements. Vacuous chewing movements in rats are widely accepted as an animal model of tardive dyskinesia. Atypical antipsychotics such as clozapine and rispiridone are associated with a lower incidence of extrapyramidal side effects and tardive dyskinesia. The present study was aimed to explore the role of 5-HT1A, 5-HT2A/2C receptors in the expression of neuroleptic-induced orofacial dyskinesia. In the present study rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to elicit vacuous chewing movements. The neuroleptic-induced vacuous chewing movements, viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5-min observation period. Acute treatment with 8 hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, dose-dependently (0.05, 0.1 and 0.2 mg/kg, i.p.) reduced the haloperidol-induced vacuous chewing movements and headshakes. Both acute and chronic administration of seganserin, ketanserin and ritanserin, 5-HT2A/2C receptor antagonists, also reduced haloperidol-induced vacuous chewing movements in a dose-dependent (0.05, 0.1 and 0.2 mg/kg, i.p.) manner. In acute studies a higher dose of ritanserin (1 mg/kg) but not ketanserin (1 mg/kg) increased vacuous chewing movements, whereas a higher dose of seganserin (1 mg/kg) did not have any effect on vacuous chewing movements. All the drugs reduced haloperidol-induced headshakes in a dose dependent fashion. These findings indicate that the serotonergic system, and particularly 5-HT1A and 5-HT2A/2C receptors, may be involved in haloperidol induced orofacial dyskinesia, and that 5-HT receptors may provide novel targets for the development of drugs that can be used to reverse or prevent the extrapyramidal side effects associated with long-term antipsychotic treatment. PMID- 11779041 TI - Effects of sydnocarb and D-amphetamine on the extracellular levels of amino acids in the rat caudate-putamen. AB - The neurotoxic effects of psychostimulants at high dosages limit their clinical applicability but the mechanism of neurotoxicity is still unsettled. We now studied by microdialysis how acute and subchronic (four times at 2-h intervals) administrations of D-amphetamine and sydnocarb [3-(beta-phenylisopropyl)-N phenylcarbamoylsydnonimine], an original novel Russian psychostimulant, affected the extracellular levels of amino acids in the caudate-putamen of halothane anesthetized male Sprague-Dawley rats. Acute D-amphetamine administration (5.0 mg/kg, i.p.) produced a moderate accumulation of extracellular glutamate and aspartate. Sydnocarb (23.8 mg/kg, i.p., a dose equimolar to 5.0 mg/kg D amphetamine) also increased extracellular glutamate and alanine. Subchronic D amphetamine administration (5.0 mg/kg x 4, i.p.) caused gradual fivefold increases in the glutamate and taurine levels and moderate increases in the aspartate and alanine levels. Subchronic sydnocarb administration (23.8 mg/kg x 4, i.p.) elicited a marked increase in the aspartate level and a small increase in the level of glutamate. The alanine level increased temporarily after each administration of sydnocarb, while the taurine level increased only after the last injection. We conclude that the mode of action of sydnocarb differs from that of D-amphetamine. Sydnocarb also seems to be less neurotoxic than D amphetamine, since it elicits lesser changes in the extracellular level of glutamate. PMID- 11779042 TI - Trafficking of green fluorescent protein-tagged muscarinic M4 receptors in NG108 15 cells. AB - The muscarinic M4 receptor for acetylcholine was tagged at its C terminus with green fluorescent protein (GFP) and expressed in NG108-15 cells, which normally express this receptor subtype. The binding affinity of the antagonist N methylscopolamine was not significantly affected by the presence of the GFP tag, whereas the affinity of the receptor for the agonist carbachol was reduced by four-fold. Stimulation of the tagged receptor resulted in inhibition of adenylyl cyclase. Following agonist stimulation, the tagged receptor was slowly internalized, and became partially co-localized with the endosomal marker Texas Red-transferrin after 30 min. There was little co-localization with the lysosomal marker 1gp120 even after 60 min of internalization. Finally, the tagged receptor, unlike the endogenous receptor, failed to recycle to the plasma membrane on removal of the agonist. We conclude that the GFP-tagged muscarinic M4 receptor does not traffic normally in NG108-15 cells, most likely because of its gross overexpression. PMID- 11779043 TI - The neurotensin receptor antagonist, SR48692, attenuates the expression of amphetamine-induced behavioural sensitisation in mice. AB - The effects of acute administration of the neurotensin receptor antagonist, SR48692 (2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3 carbonyl]amino]adamantane-2-carboxylic acid), on amphetamine-induced behavioural sensitisation were studied with the locomotor activity of mice in an open-field as an experimental parameter. The animals were repeatedly pretreated with saline or amphetamine (2.0 mg/kg, i.p. once a day, every other day for 13 days) and 2, 9 and 16 days after the last injection they received an acute i.p. administration of saline or 0.3 mg/kg SR48692 15 min before a challenge i.p. injection of 2.0 mg/kg amphetamine. Locomotor activity of the amphetamine-challenged mice was significantly higher in amphetamine-pretreated animals than in saline-pretreated mice on days 9 and 16 after withdrawal. SR48692 prevented the expression of this behavioural sensitisation. In addition, in saline-pretreated mice, the first two challenge injections of amphetamine sufficed to induce a sensitized locomotor response to the third challenge injection of the drug. SR48692 administration before amphetamine challenge injections prevented the development of this challenge injection-induced sensitisation in saline-pretreated mice but not in amphetamine-pretreated animals. In order to determine the effects of SR48692 on the expression of amphetamine-induced behavioural sensitisation in the absence of this challenge injection-induced sensitisation, the experiment was redone with a single challenge test 9 days after pretreatment. Once again, SR48692 prevented the expression of amphetamine-induced behavioural sensitisation. These results suggest that neurotensinergic transmission has a critical role in both the initiation and expression of locomotor sensitisation to amphetamine. PMID- 11779044 TI - Murine mucopolysaccharidosis VIL: impact of therapies on the phenotype, clinical course, and pathology in a model of a lysosomal storage disease. AB - The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosaminoglycans. Patients with mucopolysaccharidosis typically have widespread lysosomal storage, skeletal and central nervous system disease, and hepatosplenomegaly. Some patients with mucopolysaccharidosis may benefit from enzyme replacement therapy or bone marrow transplantation. Animal models of mucopolysaccharidosis have proven valuable for the evaluation of the effectiveness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful because of its well-defined genetics and its well-characterized clinical, pathologic, and biochemical alterations, which resemble those seen in patients with mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of therapies have been tested using this model, including enzyme replacement therapy, bone marrow, stem cell, and neural progenitor cell transplantation, and a variety of viral-mediated gene therapies. The inferences drawn from these therapeutic studies using the murine MPS VII model are likely generalizable to other lysosomal storage diseases. PMID- 11779045 TI - Gains of chromosome 8 are confined to mesenchymal components in pleuropulmonary blastoma. AB - Pleuropulmonary blastoma, an aggressive tumor that is emerging as a distinct entity of childhood, is characterized by mesenchymal elements (including undifferentiated blastema and often cartilaginous, rhabdomyoblastic, or fibroblastic differentiation) and epithelium-lined spaces. We investigated two patients with pleuropulmonary blastoma, a 3-year-old boy and an 11-year-old girl, both with large cystic masses replacing one lung. In both children, the post chemotherapy resection specimens showed more maturation of rhabdomyoblasts and more nuclear pleomorphism in all mesenchymal cell lines, compared with biopsies sampled before treatment. Karyotypic analysis demonstrated gains in chromosome 8 in both cases and 17p deletion in one case. Fluorescent in situ hybridization analysis demonstrated that the chromosome 8 gains were present in all mesenchymal elements, including undifferentiated blastematous, rhabdomyoblastic, fibroblastic, and chondroblastic areas. Epithelial cells showed no chromosome 8 gains. The chromosome 8 aberrations were not appreciably different in pre- versus post-chemotherapy tissue. Our findings substantiate previous reports that polysomy of chromosome 8 is a consistent feature of pleuropulmonary blastoma. Further, they indicate that clonal proliferation in pleuropulmonary blastoma is restricted to the malignant mesenchymal elements, supporting the notion that the epithelial components of this tumor are non-neoplastic. PMID- 11779046 TI - RET(Men2B)-transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf-/- or gfr alpha-1(-/-) mice. AB - Multiple endocrine neoplasia type 2B (MEN2B) syndrome is caused by a missense mutation in the RET gene, which replaces Met918 by Thr in the intracellular kinase domain of the protein. This single amino acid substitution transforms the receptor into a constitutively active monomeric kinase (RET(Men2B)) and produces an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies, and mucosal ganglioneuromas. The ligand, GDNF, stimulates RET activity through a co-receptor, GFR alpha-1. In vitro studies have shown that the kinase and mitogenic properties of RET(Men2B) are enhanced by GDNF/GFR alpha-1 stimulation. A relevant clinical question is whether ablation of either GDNF or GFR alpha-1 could alter penetrance or severity of the MEN2B syndrome. We report that ganglioneuromatous tumors caused by a RET(Men2B) transgene in mice are not affected grossly or microscopically by the absence of gdnf or gfr alpha-1. Loss-of-function mutations in ret, gdnf, or gfr alpha-1 cause pan-intestinal aganglionosis in mice. We find that expression of the RET(Men2B) transgene in enteric neural progenitors, after they colonize the gut, does not prevent intestinal aganglionosis associated with gdnf or gfr alpha 1 deficiency. PMID- 11779047 TI - Echovirus hepatic failure in infancy: report of four cases with speculation on the pathogenesis. AB - Disseminated echovirus infection with fulminant hepatic failure occurs almost exclusively in newborns. Although a relatively uncommon condition, it is on occasion associated with neonatal death accompanied by diffuse and extensive hemorrhagic necrosis of the liver and adrenals as the defining finding. We report four cases of severe systemic neonatal echovirus infection and present histologic and clinical evidence to demonstrate the two histologic patterns of liver involvement; intravascular coagulation in the early clinical course and a veno occlusive component in later stages of the disease. Viral damage to vascular endothelium and hepatic venous endothelium by a "hit-and-run" process in the early viremic phase rather than direct hepatocyte injury is postulated to be a mechanism. PMID- 11779049 TI - Patterns of congenital lower urinary tract obstructive uropathy: relation to abnormal prostate and bladder development and the prune belly syndrome. AB - The pathogenesis of lower urinary tract obstruction is disputed, particularly its relation to both abnormal prostatic development and the prune belly syndrome (PBS). In an attempt to clarify this issue we examined 11 males (17-38 weeks gestation) with PBS who were autopsied at our institution. The lower urinary tract was embedded intact and prepared as serial histologic sections. Of the 11 cases, 8 demonstrated mechanical obstruction of the lower urinary tract. In five of these eight cases, a "flap-valve" structure was formed by an abnormal angulation between the prostatic and penile portions of the urethra. These had dilated, thin-walled bladders and prostates and moderate to severe renal dysplasia. One of the eight cases had a valve-like obstruction at the level of the mid-prostatic urethra associated with a complex cloacal malformation and a thin-walled bladder, another case had an epithelial plug at the penile meatus, and the last of the eight cases had a posterior urethral valve. The three remaining cases showed no mechanical obstruction. However, each had megacystis with marked thickening, interstitial fibrosis, and disarray of smooth muscle bundles in the bladder wall. In 10 cases, the prostate had no or only sparse, flattened glands. These results suggest that the abnormal development of the prostate in PBS may be explained as a pressure-induced dysplasia rather than a primary maldevelopment. The findings further suggest that abnormal prostatic development and the prune belly syndrome may arise from either anatomic obstruction of various types or functional obstruction from megacystis. PMID- 11779048 TI - Cyclooxygenase-2 expression in the developing human kidney. AB - Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and COX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies that this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidneys of human fetuses exposed to non steroidal anti-inflammatory drugs (NSAIDs) in the third trimester of pregnancy. However, only minimal amounts of COX-2 mRNA or protein have been reported in the adult human kidney. We hypothesized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 weeks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a progressive decrease in COX-2 immunoreactivity from the most immature nephrons adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this temporal and spatial expression of COX-2 in the fetal kidney suggests that this enzyme may be involved in nephrogenesis, and its inhibition by NSAIDs during the third trimester may be responsible for fetal renal syndromes. PMID- 11779050 TI - Placental lesions associated with abnormal growth in twins. AB - Abnormal growth in one or both twins may contribute to the increased morbidity and mortality observed in twin gestation. Our objective in this retrospective study of all twin pregnancies delivered at our hospital (n = 240) over a 2-year period was to study the relationship between placental lesions and abnormal growth. Standardized placental examinations were performed in 192 cases (80%), which constituted the study population. Two growth abnormalities were studied: discordant growth as defined by > 15% difference in birth weight and small-for gestational-age (SGA) birth as defined by birth weight less-than the 10th percentile for gestational age. The majority of twin pregnancies with either discordant growth (41/57 cases) or SGA birth (26/35 cases) had dichorionic placentas. In monochorionic placentas studied by injection there was no significant relationship between vascular anastomoses and discordant growth. Placental weight for small discordant and SGA twins was equivalent or increased relative to infant weight, a pattern not suggestive of maternal vascular underperfusion. Eight lesions, five considered to represent chronic placental disease and three considered to represent intrauterine adaptation, were studied as possible predictors of abnormal growth. The overall prevalence of these lesions in twin placentas was less than that seen in singleton births. Concordance between twin placentas for most lesions was higher than would be expected, based on their prevalence in singleton placentas. Two lesions were associated with discordant growth in both univariate and multivariate analyses: peripheral cord insertion (OR 3.6, 95% CI 1.7-7.6) and avascular villi (AV; OR 3.2, 95% CI 1.0-10.3). Three placental lesions were associated with SGA infants at the univariate level: peripheral cord insertion, avascular villi, and maternal vascular underperfusion. Only peripheral cord insertion (OR 9.8, 95% CI 4.1-23.4) and AV (OR 3.7, CI 1.0-13.7) were significant in the multivariate analysis. The relative increase in peripheral cord insertion and AV with abnormal growth was observed for both monochorionic and dichorionic placentas. Subgroups of discordant infants with and without SGA were both associated with peripheral cord insertion while only those with SGA had an increase in AV. Both peripheral cord insertion and AV were increased in the subgroup with SGA but no discordancy. In summary, two placental lesions, peripheral cord insertion indicating a spatially limited intrauterine compartment and AV indicating occlusion of fetal vessels in the placenta, were associated with abnormal growth in twins. PMID- 11779052 TI - Pediatric angiosarcoma of the heart: a unique presentation and metastatic pattern. AB - We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII-related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed. PMID- 11779051 TI - Undifferentiated embryonal sarcoma with unusual features arising within mesenchymal hamartoma of the liver: report of a case and review of the literature. AB - Undifferentiated embryonal sarcoma (UES) is a rare and highly malignant hepatic neoplasm, affecting almost exclusively the pediatric population. It has replaced malignant mesenchymoma, under which diagnostic term the first three cases were described. A link between embryonal sarcoma and mesenchymal hamartoma of the liver (MHL) has long been proposed, because of clinicopathologic overlaps of these entities; however, until recently, this association remained tenuous. Cases of UES arising in a background of mesenchymal hamartoma of the liver have previously been reported in two teenage girls. Discovery of a similar genetic abnormality in MHL and UES has clinched the supposed link between them. There have also been two reports of UES with prominent cystification, one associated with peripheral eosinophilia, and thereby masquerading as hydatid cyst of the liver. We report a case of UES arising in a young boy with MHL, with unusual histologic features, including large mesothelial-lined cysts and ectopic adrenal cortical tissue under Glisson's capsule. PMID- 11779053 TI - Bizarre parosteal osteochondromatous proliferation: case report and review of the literature. AB - Bizarre parosteal osteochondromatous proliferation of bone (BPOP) is a benign lesion that is occasionally misinterpreted as a malignant process. The original reports described lesions exclusively in the hands and feet. However, subsequent reports have included additional sites in the long bones, skull, and maxilla. The differential diagnosis of BPOP includes numerous benign and malignant lesions. The benign differential diagnosis includes osteochondroma and reactive processes. The most important malignant differential diagnosis is parosteal osteosarcoma. We present a case of an 11-year-old boy with recurrent BPOP and review the literature. We discuss the differential diagnosis and pathogenesis of the lesion. PMID- 11779054 TI - Massive osteolysis of skull bones secondary to lymphangioma of paranasal sinuses and mastoid sinus: report of two cases in children. AB - Massive osteolysis (MO) is a rare condition in which progressive localized bone tissue resorption is associated with proliferating thin-walled vessels in the absence of inflammation. Rare cases have been reported to occur in the skull. This paper describes two patients with MO who presented with massive assymetric swelling of the skull. This was associated with extensive enlargement of the paranasal sinuses (frontal, ethmoidal, and sphenoidal in one and the mastoid air cells in the other). The second patient developed subcutaneous emphysema on several occasions and the Valsalva maneuver increased the swelling, indicating transmission of the air from the nasopharynx to the mastoid cells and from there to the subcutaneous tissue. In the first patient, the sinus mucosa was shown to be involved by an extensive lymphangioma, and a similar change was seen in the mastoid air cells (patient 2). We are proposing that MO of these two patients resulted from bone resorption due to progressive extension of sinus mucous lymphangiomata. PMID- 11779055 TI - Expression of CD5 on hematogones in a 7-year-old girl with Shwachman-Diamond syndrome. AB - We report increased numbers of hematogones in a 7-year-old girl with pancytopenia due to Shwachman-Diamond syndrome. Her hematogones expressed the T-cell marker CD5 as well as CD19, CD10, and CD20, and terminal deoxynucleotidyl transferase and HLA-DR. These findings suggest that hematogones are precursors of both CD5 positive B cells and CD5-negative B cells. Thus CD5-positive B cells in bone marrow may be derived from bone marrow stem cells, and not from the residual fetal B cells of yolk sac/liver origin. The finding of CD5 expression on hematogones also raises the possibility that neoplastic B cells of chronic lymphocytic leukemia, which characteristically co-express CD5 and CD19, may be derived from CD5-positive B-cell precursors in bone marrow and not from mature B cells in lymph nodes. PMID- 11779057 TI - Method for processing the brain at the time of autopsy. PMID- 11779056 TI - Evaluation of mystery of the hernia sac through another perspective. PMID- 11779058 TI - Toxicologic significance of the hyperglycemia caused by organophosphorous insecticides. PMID- 11779059 TI - Acetylcholinesterase of Mytilus galloprovincialis LmK. hemolymph: a suitable environmental biomarker. PMID- 11779060 TI - Effect of 1,1,1-trichloroethane on calcium current of rat dorsal root ganglion neurons. PMID- 11779061 TI - Effects of acute exposure to a commercial formulation of glyphosate on the tadpoles of two species of anurans. PMID- 11779062 TI - Chronic lead exposure, body condition, and testis mass in wild mallard ducks. PMID- 11779063 TI - Alleviation of cadmium-induced decrease in biomass of Pisum and Sesamum by inorganic nutrients. PMID- 11779065 TI - Mercury levels in Gafftopsail catfish (Bagre marinus) from Tarpon Bay, Sanibel, Florida, USA. PMID- 11779064 TI - Cadmium, copper, and zinc in Eurasian beaver (Castor fiber) from Bo, Telemark, Norway. PMID- 11779066 TI - Copper and mercury complexing capacity of organic matter from a mangrove mud flat environment, Sepetiba Bay, Brazil. PMID- 11779067 TI - Use of microtox for assessing heavy metal complex formation with the organic solvents acetontrile and dimethyl sulphoxide: a preliminary study. PMID- 11779068 TI - Heavy metal contamination of pasture soils by irrigated municipal sewage. PMID- 11779069 TI - Chromium (VI) in waters in parts of Sukinda chromite valley and health hazards, Orissa, India. PMID- 11779070 TI - Factors influencing the formation of trihalomethanes in drinking water treatment plants. PMID- 11779071 TI - Monitoring of market fish samples for endosulfan and hexachlorocyclohexane residues in and around Calcutta. PMID- 11779072 TI - Petroleum hydrocarbon concentrations in Arabian Gulf fish tissues. PMID- 11779073 TI - Isolation of a new organochlorine pollutant 2,3,3,3,2',3',3',3' octachlorodipropyl ether from fish. PMID- 11779074 TI - Influence of methyl tert-butyl ether on lake water algae. PMID- 11779075 TI - Acute toxicity of cadmium, mercury, and lead to whiteleg shrimp (Litopenaeus vannamei) postlarvae. PMID- 11779076 TI - Monitoring of pesticide residues in summer fruits and vegetables from Kanpur, India. PMID- 11779077 TI - Susceptibility of Florida Candler fine soil to herbicide leaching. PMID- 11779078 TI - Photodegradation of acetochlor and butachlor in waters containing humic acid and inorganic ion. PMID- 11779079 TI - Persistence, mobility, and adsorption of the herbicide flufenacet in the soil of winter wheat crops. PMID- 11779080 TI - Advances in the use of angiogenesis inhibitors in cancer. PMID- 11779082 TI - Angiogenesis inhibition in solid tumors. AB - Angiogenesis plays a central role in a variety of physiologic and pathologic disease states. Because the growth and metastasis of malignant neoplasms require the presence of an adequate blood supply, pharmacologic inhibition of tumor induced angiogenesis represents a promising target for antineoplastic therapy. A number of approaches to such inhibition are therefore under active investigation. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are among the best characterized of the various key elements in benign and neoplastic angiogenesis. In 1997, clinical trials were initiated to evaluate an anti-VEGF monoclonal antibody and a VEGFR-2 antagonist as therapy for patients with different types of solid tumors and hematologic neoplasms. Dose selection for these cytostatic agents requires translation from preclinical models, as these agents are likely to require chronic dosing at an optimal biological dose, rather than a maximally tolerated dose. For example, SU5416, a novel small-molecule inhibitor of VEGFR-2, administered at 145 mg/m2 intravenously twice weekly, is well tolerated and achieves the concentration levels required to inhibit endothelial cell proliferation in preclinical models. Because the mechanism of action of angiogenesis inhibitors is complementary to that of classic cytotoxic chemotherapy, preclinical models and subsequent clinical trials frequently explore combinations of these agents with cytotoxic chemotherapy, hoping to achieve additive or synergistic antitumor activity. It is hoped that the combination of angiogenesis inhibitors with cytotoxic chemotherapeutic agents will significantly improve survival and quality of life for cancer patients. As a result of favorable results from Phase 1 and 2 studies, randomized, multicenter clinical investigations of angiogenesis inhibitors are ongoing. PMID- 11779081 TI - Endothelial survival factors as targets for antineoplastic therapy. AB - Angiogenesis is essential for the growth and metastasis of solid tumors. The angiogenic process includes not only development of new blood vessels but also maintenance of the existing vasculature. Recent studies have demonstrated that several factors induce angiogenesis and also function as endothelial cell survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is an endothelial cell survival factor whose tyrosine kinase receptors are limited to endothelial cells. Members of the angiopoietin family also bind to an endothelial cell-specific tyrosine kinase receptor. Angiopoietin-1 has been shown to stabilize endothelial cell networks, whereas angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes endothelial cell networks. Pericytes contribute to endothelial cell stabilization by cell-cell contact, secretion of survival factors, or both. In addition, integrins may function as endothelial cell survival factors by numerous mechanisms after binding to the extracellular matrix. The effects of many endothelial cell survival factors act in concert with vascular endothelial growth factor to enhance this essential step in angiogenesis. Targeting any of the aforementioned mechanisms for endothelial cell survival may provide novel therapeutic antineoplastic strategies. PMID- 11779083 TI - Role of angiogenesis inhibitors in acute myeloid leukemia. AB - Neovascularization is increasingly recognized as an important factor in the pathogenesis of hematologic malignancies as well as solid tumors. The complex interactions between several cell types and numerous cytokine mediators suggest the involvement of autocrine and paracrine signaling mechanisms. Vascular endothelial growth factor (VEGF) in particular is critical to both stimulation of leukemic growth and proliferation of endothelial cells. Tyrosine kinase receptors specific for certain growth factors represent attractive target molecules for anticancer therapy. SU5416 is a competitive inhibitor of VEGF receptor subtypes VEGFR-1 and VEGFR-2 and stem cell factor receptor c-kit. Preclinical evidence shows that SU5416 effectively inhibits VEGF-induced endothelial cell proliferation and slows growth of subcutaneous solid tumor xenografts. This agent is in late-stage clinical trials in patients with solid tumors, and a Phase 2 study was recently initiated to evaluate its utility in the treatment of acute myeloid leukemia. In this Phase 2 study, investigators are seeking to determine the response rate to the antiangiogenic agent SU5416. Translational research in this study is intended to aid our understanding of the precise mechanisms by which SU5416 affects acute myeloid leukemia cells and the bone marrow microenvironment. PMID- 11779084 TI - SU6668, a multitargeted angiogenesis inhibitor. AB - Angiogenesis plays a critical role in the growth and metastasis of solid and hematologic malignancies. This complex and highly regulated process involves numerous different cell types and mediators. Vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor are among the soluble factors that stimulate this process. They are ligands for specific tyrosine kinase receptors that are important in transduction of intracellular signals and induction of angiogenesis. SU6668 is a novel molecule that competitively inhibits the tyrosine kinase of the receptors for vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, and c-kit. In vitro studies have confirmed that SU6668 inhibits growth factor-stimulated tyrosine phosphorylation. SU6668 also has significant antitumor activity against many types of tumor xenograft explants in athymic mice. SU6668 inhibits angiogenesis through several mechanisms, including the induction of apoptosis in vascular endothelial cells and tumor cells. Currently, Phase 1 studies are being initiated to evaluate the potential of SU6668 as an anticancer agent for humans. PMID- 11779085 TI - Integrins as targets of angiogenesis inhibition. AB - Integrins area widely distributed family of cell surface alpha/beta heterodimers that bind cells to components of the extracellular matrix and mediate cell-cell interactions. Integrin alpha(v)beta3 interacts with RGD (Arg-Gly-Asp) sequence containing proteins in the extracellular matrix. The distribution of alpha(v)beta3 is highly restricted, with expression on activated endothelium, activated vascular smooth muscle, tumors, and osteoclasts. Expression of alpha(v)beta3 may contribute to a malignant phenotype by supporting the growth and persistence of small blood vessels that nourish the primary and metastatic tumors and increasing invasive potential. Inhibition of alpha(v)beta3 can modulate tumor-induced angiogenesis and can increase apoptosis of tumor associated small blood vessels. It might also help control humoral hypercalcemia of malignancy through direct or indirect activity on the osteoclast. Preclinical studies found that several RGD peptidomimetics and a monoclonal antibody to alpha(v)beta3 can inhibit tumor growth by blocking tumor-induced angiogenesis. PMID- 11779086 TI - Approach to angiogenesis inhibition based on cyclooxygenase-2. AB - Two cyclooxygenase (COX) isoforms have been identified: COX-1 and COX-2. COX-1 is the constitutively expressed form of the enzyme and is ubiquitous in its distribution. COX-2 is inducible and is present in inflammatory foci, tumors, and neovasculature. Expression of COX-2 appears to be important in tumor promotion, growth, and metastasis. It is up-regulated in a variety of premalignant disorders and malignancies. COX inhibitors have a major role in the treatment of inflammation and pain. Epidemiologic evidence in patients who take nonsteroidal anti-inflammatory drugs links COX inhibition with decreases in malignant esophageal, stomach, colon, lung, and breast tumors. Nonselective COX inhibitors have demonstrated efficacy in control of familial adenomatous polyposis, a disorder associated with the development of thousands of benign intestinal polyps. The selective COX-2 inhibitor celecoxib (Celebrex, Pharmacia) has been shown to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib has recently been approved for this indication and offers the potential for equivalent or greater efficacy than that seen with nonselective COX inhibitors but without the gastrointestinal mucosal toxicity and the inhibition of platelet function associated with those agents. Angiogenesis is a feature of both benign and malignant disease. Because COX-2 is up-regulated in the neovasculature of the rheumatoid pannus and in malignant tumors and their surrounding stroma, selective COX-2 inhibitors may be able to modify the progression of these disorders through the control of angiogenesis. PMID- 11779087 TI - Assaultive behavior by psychiatric in-patients and its related factors. AB - The purpose of this article is to explore assaultive behavior of psychiatric in patients in a hospital and to examine the interplay of patient, environmental, and staff factors related to assault. The present study was carried out prospectively using standardized instruments applied in four acute wards in one hospital. A log system was used to record the occurrence of assaults. The results showed 595 episodes of assault from 238 patients in 7 months. Forty one nurses participated in the study. To further examine the differences between assaultive and non-assaultive patients, and assaulted and non-assaulted nurses, a logistic regression analysis was used. The results indicated that patient factors (diagnosis, history of assault, time since admission, and history of smoking), environmental factors (patient/nurse ratio and spatial density), and staff factors (age, length of work experience, training program received in prevention and management of assaults) are contributing variables to assaultive behavior. The present study examined a wider range of variables than have been included in many previous studies. This reinforces the necessary complexity of models likely to prove useful in predicting assaults among psychiatric inpatients. PMID- 11779088 TI - "Burnout" in intensive care nurses. AB - The purpose of this research was to examine the relationship between burnout components and selected demographic variables in a group of intensive care unit nurses. This research hopes to heighten awareness of both intensive care nurses and hospital administrators of the importance of burnout in their work setting. A descriptive correlational study design was used to examine the extent of burnout according to selected demographic variables. Sixty-eight intensive care nurses from two hospitals and critical care courses at one university completed a demographic data form and the research questionnaire of the Maslach Burnout Inventory (MBI). Statistical analysis included non-parametric tests. Study results indicated low to moderate levels of total component scores in all intensive care nurses and on all three subscales of the assessment instrument. Results also indicated that, in this sample, younger nurses (20-29 years of age), separated and divorced nurses, and staff who work full time in ICUs were the most prone to emotional exhaustion. These research findings recommend support for ICU nurses to prevent burnout in their work setting. Further research is necessary to examine what kinds of working environments (job related stress) are effective in mitigating burnout amongst staff in the intensive care field. PMID- 11779089 TI - The impact of concept of health on health behavior. AB - Although previous studies have examined selected factors influencing health behavior, the complex interplay of the concept of health and health behavior in persons with chronic illness has not been investigated. The purpose of this study was to investigate the individual effects of six factors in the concept of health on the health behavior of Taiwanese people with chronic illness. A sample of 372 persons with chronic illness completed instruments measuring their concept of health and health behavior. Six proposed models were assessed using the maximum likelihood estimation, which is implemented by LISREL 8.3. The overall fit of the models tested in this study lends support to the assertion that the factors of the concept of health affect health behavior. Zest for life, serenity and meaning were the strongly affecting factors. These factors each accounted for 34-43% of the variance in health behavior. The results of this study support the notion that the health behavior of people with chronic illness can be predicted by their concept of health. Further research using a longitudinal design is needed to clarify the causal relationship between the concept of health and health behavior in Taiwanese people with chronic illness. PMID- 11779090 TI - Relationships between quality of sleep and its related factors among elderly Chinese immigrants in the Seattle area. AB - The risk factors related to quality of sleep in elderly adults, such as life style events, physical illness, psychological factors, and gender have been well identified by several studies. However, information regarding the relationship between quality of sleep and its related factors among elderly Chinese immigrants is not available in recent sleep literature. The purposes of this study were to explore the quality of sleep and discover the relationships between sleep quality and its related factors among elderly Chinese immigrants people in the Seattle area. Pearson's correlation and descriptive statistics were used to analyze data. Eighty community-dwelling Chinese elderly people, aged from 66 to 93, were recruited from the Chinese Senior Day Care Center, local Chinese churches, elderly Chinese individuals' private homes, and Chinese retirement apartments within the Seattle area. Three questionnaires were utilized to collect data, and personal interviews were used to facilitate the subjects in completing the questionnaires. The findings of this study showed that (1) 55% (n = 44) of the participants were identified as poor sleepers and 45% (n = 36) as good sleepers. (2) depression and the number of current diseases experienced by the subjects were in statistically significant correlation with quality of sleep, with r = .477, p = .00 and r = .221, p = .049 respectively. (3) daytime napping did not affect nighttime sleep in this study' population. The findings of this study can provide information regarding sleep problems among elderly Chinese immigrants to improve the elderly's quality of sleep. PMID- 11779091 TI - Effectiveness of family care intervention program on activity of daily living among disabled patients. AB - The objective of this prospective study was to compare the improvement of activity of daily living (ADL) scores between two groups of disabled patients who participated in a family care intervention program. 137 patients were selected from health stations and Activity of Daily Living (ADL) scores were assessed eight times over a period of 22 weeks. Family caregivers were trained to provide home nursing care for the disabled. The patients were divided into two groups: early-stage (intervention started less than 6 months from diagnosis) and late stage (intervention started 7-24 months from diagnosis). Over the duration of the intervention program, the results, using ANCOVA test, showed that the ADL score of the early-stage had group increased by 12.9, compared to the later-stage group, which increased by 3.0 (p < .000). At one-year follow-up, the ADL score of the early-stage group increased by a greater extent (6.2) than the later-stage group (1.3). The factors that affected ADL scores of the survivals were as follows: age, baseline ADL score and duration of disability. The authors conclude that the intervention program was most effective in improving ADL score when intervention was implemented early. PMID- 11779092 TI - Toward an understanding of mothering: the care giving process of mothers with autistic children. AB - The purpose of this study was to explore the care-giving experience of mothers with autistic children. In this qualitative study, a focus group and in-depth interviews were conducted with mothers with an autistic child to uncover the nature of their mothering experience. Data were analyzed for themes with the constant comparison approach of grounded theory. Three themes emerged: (a) the perception about their disabled child; (b) their special concerns for caring for this child and (c) reclaiming and discovering self through understanding the meaning of mothering. The results can help health workers to gain a deeper understanding of the care-giving process for mothers with an autistic child and facilitate mothers to find the meaning of care and their well-being. PMID- 11779093 TI - Recent advances in DNA microarrays. AB - The structure of the human genome is almost completely elucidated and the life sciences will now aim for a general and integrated study of gene expressions and the functional elucidation of proteins. In such a study, various new techniques have been developed, and DNA microarray technology is the most representative one. As for the DNA microarray techniques, several thousands to tens of thousands of gene segments are immobilized on a glass slide at high density, and cDNA probes prepared from specific cells or tissues are hybridized on the slides from which gene expression profiles are obtained at one sweep in a short time. The present development of this technique and its possible application to medicine related fields are described. PMID- 11779094 TI - A new classification of free combined or connected tissue transfers: introduction to the concept of bridge, siamese, chimeric, mosaic, and chain-circle flaps. AB - Recently, combined tissues or flaps have been used for the repair of extensively massive or wide defects resulting from radical wide resection. To further advance the development of combined tissue transfers, they should be reclassified. Based on our cases with free tissue transfers, we have created a new classification of combined flaps composed of "bridge", "chimeric", "siamese", "mosaic", and "chain circle" flaps. The bridge flap is fabricated out together of separate flaps with short vascular pedicles. These form a compound flap supplied with a solitary vascular source. The chimeric flap is compounded from multiple different flaps but consists of only a single different tissue form. Each of the flaps is usually supplied by different branches from the same source vessel. It differs from the bridge flap in that the pedicle of each flap or tissue has some length for its movement for transfer. The siamese connected flap has 2 adjacent flaps that are simultaneously elevated, and a disparate vascular pedicle for each flap must be reestablished. This connected flap has double isolated pedicles. Themosaic connected flap consists of 2 adjacent flaps that are simultaneously elevated, and the pedicle of the distal flap is anastomosed to the pedicle branch of the proximal flap in the "bridge" fashion. The vascular pedicle of the proximal flap is anastomosed to a single vascular source. The chain-circle flap has 2 or more flaps like the bridge and chimeric flaps, and the distal end of the vascular source is anastomosed to the branch of the recipient vessel. Based on results with our patients, the lateral circumflex femoral system seems to be the most suitable candidate for the axial pedicle of these combined flaps, because the system has several branches of large and small caliber, and several tissue components, such as the vascularized ilium, rectus femoris muscle, gracilis muscle, lateral femoral cutaneous nerve, and fascia lata, are located nearby. PMID- 11779095 TI - Expression of caspase-3 and -9 relevant to cartilage destruction and chondrocyte apoptosis in human osteoarthritic cartilage. AB - To clarify the involvement of the caspase family in the pathway of NO-induced chondrocyte apoptosis, osteoarthritis (OA) cartilage obtained from 8 patients undergoing total hip arthroplasty were used for histopathological study. Cartilage samples taken from non-fibrillated areas of femoral head resected during surgery for femoral neck fracture were used for comparison. DNA fragmentation of chondrocytes was detected by the nick end-labeling (TUNEL) method. Apoptosis was further confirmed by transmission electron microscopy. The distributions of nitrotyrosine (NT), caspase-3, and -9 were examined immunohistochemically. The populations of apoptotic as well as NT-, caspase-3-, and -9-positive cells were quantified by counting the number of cells in the superficial, middle, and deep layers, respectively. The TUNEL-positive cells were observed primarily in superficial proliferating chondrocytes, clustering chondrocytes, and deep-layer chondrocytes of OA cartilage. Few positive cells were seen in the proliferating chondrocytes in the middle layer. Positive reactions for caspase-3 and -9 were observed in chondrocytes in similar areas. Histological OA grade showed significant correlations with the mean populations of apoptotic chondrocytes (% apoptosis) over the 3 areas. The populations of NT positive cells (% NT) over the same areas also showed significant correlation with OA grade. Positivity for caspase-3 closely correlated with the OA grade, % apoptosis and %NT. It was concluded that caspase-3 and -9 could play a role in NO induced chondrocyte apoptosis in OA cartilage. PMID- 11779096 TI - Therapeutic effects of azathioprine in combination with low-dose prednisolone in patients with intractable autoimmune hepatitis type 1. AB - This study evaluated the effects of azathioprine in combination with low-dose prednisolone in the management of patients with intractable autoimmune hepatitis. Thirteen patients with intractable autoimmune hepatitis who had an incomplete or arrested response to conventional prednisolone therapy, or who relapsed during prednisolone maintenance therapy were additionally administered 50 or 100 mg/day of azathioprine in combination with prednisolone. This regimen reliably induced complete remission in 12 of 13 patients, and these 12 remained in remission during the follow-up period with maintenance therapy of 50 mg/day of azathioprine in combination with 5 mg/day of prednisolone. The findings of the current study indicate that the azathioprine and low-dose prednisolone combined therapy may offer a satisfactory alternative therapy for patients with intractable autoimmune hepatitis who have an incomplete or arrested response to conventional prednisolone therapy, or who relapse during prednisolone maintenance therapy. PMID- 11779097 TI - Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. AB - Hepatic encephalopathy is one of the major complications in decompensated liver cirrhosis. The current study was conducted to clarify the mechanisms of zinc deficiency in liver cirrhosis and its involvement in hepatic encephalopathy via ammonia metabolism. Ten patients each with compensated or decompensated liver cirrhosis and 11 healthy volunteers were enrolled in the study. Serum zinc levels and its daily urinary excretion were measured, an oral zinc-tolerance test was performed to examine zinc malabsorption, and the effects of diuretics on zinc excretion and of zinc supplementation on ammonia metabolism in the skeletal muscle were studied. The mean serum zinc levels in patients with decompensated liver cirrhosis were found to be significantly lower than the levels in controls and patients with compensated liver cirrhosis. The serum zinc levels were inversely correlated with blood ammonia in the fasting state. In the oral zinc tolerance test, the percent increase in serum zinc levels 120 and 180 min after ingestion was less in cirrhotic patients than in controls. A diuretic administration resulted in a significant reduction in serum zinc levels. An increased uptake of ammonia by and an increased release of glutamine from leg skeletal muscle after oral supplementation of zinc sulfate were evident. Taken together, zinc deficiency in decompensated cirrhotic patients appears to be due to low absorption and to high urinary excretion, for which excessive diuretic administration is, in part, responsible, and zinc supplementation might play an important role in the prevention of hepatic encephalopathy by activating glutamine synthetase. PMID- 11779098 TI - Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. AB - In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron catalyzed free radical reactions. PMID- 11779099 TI - Retroperitoneal hematoma associated with femoral neuropathy: a complication under antiplatelets therapy. AB - We report a case of retroperitoneal hematoma presenting as femoral nerve pulsy on antiplatelet therapy. The patient, a 78-year-old man who had undergone antiplatelet treatment using ticlopidine, was admitted to our hospital with complaints of sudden-onset low abdominal and back pain. Computed tomography showed an iso-density mass in the right retroperitoneum within the psoas muscle. We made a diagnosis of retroperitoneal hematoma compressing the femoral nerve and performed an operation to remove the hematoma in order to decompress the femoral neuropathy. Postoperatively, the patient rapidly recovered from the femoral neuropathy. In the particular case in which no antagonist against the ticlopidine is available, surgical decompression could produce a good outcome. PMID- 11779100 TI - Online monitoring of solid-phase peptide syntheses on glass-type surfaces using white light interference. AB - Label-free optical detection methods are of particular value for the investigation of biomolecular interactions. A label-free method based on reflectometric interference spectroscopy is described which enables both the on line monitoring of solid phase peptide syntheses and subsequently the determination of antibody binding to these peptides without cleavage from the support. The method uses SiO(2) transducers that were modified with diaminopolyethylene glycol. The stepwise coupling of different amino acids to the transducer surface was investigated and the complete monitoring of the synthesis of a viral epitope was performed. The success of the synthesis was proven via binding of a specific monoclonal antibody to the transducer-bound product. In order to demonstrate specificity the binding was inhibited with the same peptide epitope added in solution. The approach is attractive especially in the field of high throughput screening since both the synthesis and the interaction with the biological receptor can be monitored using the same technique. PMID- 11779101 TI - Effect of Cd(2+) and Hg(2+) on the activity of Na(+)/K(+)-ATPase and Mg(2+) ATPase adsorbed on polystyrene microtiter plates. AB - In the present study a polystyrene microtiter plate was tested as a support material for synaptic plasma membrane (SPM) immobilization by adsorption. The adsorption was carried out by an 18-h incubation at +4 degrees C of SPM with a polystyrene matrix, at pH 7.4. Evaluation of the efficiency of the applied immobilization method revealed that 10% protein fraction of initially applied SPM was bound to the support and that two SPM enzymes, Na(+)/K(+)-ATPase and Mg(2+) ATPase, retained 70-80% activity after the adsorption. In addition, adsorption stabilizes Na(+)/K(+)-ATPase and Mg(2+)-ATPase, since the activities are substantial 3 weeks after the adsorption. Parallel kinetic analysis showed that adsorption does not alter significantly the kinetic properties of Na(+)/K(+) ATPase and Mg(2+)-ATPase and their sensitivity to and mechanism of Cd(2+)- or Hg(2+)-induced inhibition. The only exception is the "high affinity" Mg(2+) ATPase moiety, whose affinity for ATP and sensitivity toward Cd(2+) were increased by the adsorption. The results show that such system may be used as a practical and comfortable model for the in vitro toxicological investigations. PMID- 11779102 TI - Discriminative quantification of cytochrome P4502D6 and 2D7/8 pseudogene expression by TaqMan real-time reverse transcriptase polymerase chain reaction. AB - The human drug oxidizing cytochrome P450, CYP2D6, is expressed at highly variable levels mainly due to a common genetic polymorphism which leads to the poor metabolizer phenotype in carriers of two nonfunctional alleles and to the extensive metabolizer phenotype in carriers of one or more functional alleles. Investigation of the role of CYP2D6 mRNA for expression and the possibility of using mRNA expression as a surrogate marker has been hampered by the presence of two pseudogenes, CYP2D7P and CYP2D8P. We therefore developed highly specific TaqMan real-time reverse transcriptase-PCR assays for the discriminative quantification of CYP2D6 and CYP2D7/8P transcripts. By in vitro transcription of plasmids containing the CYP2D6 cDNA or a hybrid CYP2D6/7 cDNA constructed by in vitro mutagenesis, authentic cRNAs were synthesized to be used for specificity testing and for absolute quantification. The method was used to determine CYP2D transcripts in a large number of human livers samples. CYP2D6 was not normally distributed with a median mRNA content of 3.2 transcripts per picogram of total RNA in all livers (range 0.32-14.8, N = 74). Expression in genetic poor metabolizers (1.81, N = 6) was significantly lower compared to extensive metabolizers (3.33, N = 68, P = 0.022). Similar expression levels were found for CYP2D7/8P (median 3.38 transcripts/pg, range 0.46-14.3), which were correlated to CYP2D6 mRNA (r(S) = 0.46, P < 0.0001) but did not depend on CYP2D6 genotype. These data demonstrate genotype-dependent mRNA expression for CYP2D6 and they emphasize the necessity of differentiating between the functional CYP2D6 and the CYP2D pseudogenes. PMID- 11779103 TI - Flow-mediated on-surface reconstitution of G-protein coupled receptors for applications in surface plasmon resonance biosensors. AB - To facilitate biosensor studies of G-protein coupled receptors (GPCR) and other membrane proteins, reliable methods for preparation of sensor surfaces with high protein density are required. We present here a method for the easy and rapid immobilization and reconstitution of GPCR on carboxylated dextran surfaces modified with long alkyl groups. Following amine coupling of the detergent solubilized receptor, lipid/detergent-mixed micelles were adhered as they were injected over the immobilized surface, taking advantage of the integrated flow cells. The detergent was eluted in the subsequent buffer flow and the remaining lipid formed a bilayer on the chip surface. With this procedure, rhodopsin was functionally reconstituted in a lipid environment in approximately 1 min. This method can also be used for the easy formation of pure supported lipid bilayers for use in model membrane interaction studies. PMID- 11779104 TI - A preservation method that allows recovery of intact RNA from tissues dissected by laser capture microdissection. AB - We report a novel method for preparing samples for laser capture microdissection. The procedure described here permits extraction of intact RNA while preserving morphology, thus being suitable both for identification of specific cells and for analysis of their gene expression. The method is applicable to both mouse embryos and human tumors and may improve the preparation of cDNA libraries from specific cell types without interfering with histological diagnosis. PMID- 11779105 TI - Stable expression of a synthetic gene for the human motilin receptor: use in an aequorin-based receptor activation assay. AB - A synthetic gene for the human motilin receptor containing 33 unique restriction sites was designed and stably coexpressed in HEK293 cells with the bioluminescent Ca(2+) indicator protein aequorin. The dose-dependent response of the receptor to motilin was demonstrated using transient transfections, and a stable cell line was selected. [(125)I]Motilin binding was used to estimate receptor expression level for the stable cell line, and titration of a membrane preparation indicated a K(d) value of 0.8 nM. The same cell line was used to evaluate a panel of erythromycin-derived agonists and provided EC(50) values for receptor activation that agree closely with data obtained in contractility assays. The peptide antagonist ANQ11125 (Phe3Leu13 motilin 1-14) inhibited motilin induced response with a K(i) value of 10 nM. The system is well-suited for the screening of compound libraries and receptor mutagenesis studies. PMID- 11779106 TI - A thermodynamic characterization of the binding of thrombin inhibitors to human thrombin, combining biosensor technology, stopped-flow spectrophotometry, and microcalorimetry. AB - The binding of a series of low-molecular-mass, active-site-directed thrombin inhibitors (399-575 Da) to human alpha-thrombin was investigated by surface plasmon resonance technology (BIACORE), stopped-flow spectrophotometry, and isothermal titration microcalorimetry (ITC). The equilibrium constants K(D) (nM to microM range) at 25 degrees C obtained from the BIACORE analysis correlated well with the inhibition constants K(i) in a chromogenic inhibition assay. The interactions between thrombin and three potent inhibitors, melagatran, inogatran, and CH-248, were further investigated at temperatures between 278 and 310K. A one to-one binding stoichiometry found with ITC was supported by BIACORE data. K(i) and K(D) values increased with the temperature, mainly due to higher values for dissociation rate constants. The changes in enthalpy, DeltaH, and entropy, DeltaS, determined from the linear van't Hoff plots (R coefficient > 0.99), were linearly correlated by chemical compensation. Both techniques indicated clear differences in DeltaS for the three inhibitors, with a strong correlation to the number of rotational bonds. Immobilization of thrombin increased the binding stability at higher temperature and reduced the DeltaH by 20 kJ mol(-1). DeltaH values obtained from the inhibition kinetics and BIACORE were thus not identical, but correlated well with ITC data obtained at 37 degrees C. The two thermodynamic techniques allowed further differentiation between compounds of similar affinity; furthermore, kinetic analysis, hence analysis of the transition state, is complementary to ITC. A direct BIACORE binding assay might be a useful alternative to more elaborate inhibition studies. PMID- 11779107 TI - A liquid chromatography-mass spectrometry method to measure stable isotopic tracer enrichments of glycerol and glucose in human serum. AB - Stable isotopes are commonly used as tracers for the measurement of glycerol and glucose kinetics in metabolic studies. Traditionally, the analysis of these isotopes has been performed using gas chromatography-mass spectrometry, which requires that the analytes first be derivatized. The derivatization process adds considerable complexity to the method. Liquid chromatography-mass spectrometry (LCMS) can measure many metabolites directly with limited sample preparation. We present a novel analytical method for the measurement of [1,1,2,3,3 (2)H(5)]glycerol (d(5)-glycerol) and [6,6-(2)H(2)]glucose (d(2)-glucose) isotopic tracer enrichments in human serum in a single run by LCMS. After a simple extraction step, the sample is separated isocratically by HPLC, and the isotopes are measured using positive electrospray ionization with selected ion monitoring of the sodium-adduct ions. The method is linear over a wide range of d(2)-glucose and d(5)-glycerol enrichments. The within-day standard deviation of measurement of serum samples was 0.05 mole% excess (MPE) for d(2)-glucose and 0.25 MPE for d(5)-glycerol. The variation of tracer enrichment among days was about double that measured within 1 day. PMID- 11779108 TI - Time-lapse imaging of conformational changes in supercoiled DNA by scanning force microscopy. AB - Most of the scanning force microscopy (SFM) images of supercoiled DNA on untreated mica thus far reported have not shown tight plectonemic structure seen by electron microscopy, but instead less coiled molecules and sometimes a partly "condensed" state with intimate chain-chain interactions. By observing time-lapse images of conformational changes of DNA induced by decreasing ionic strength of imaging buffer in solution SFM, we could show that the process of water rinsing, an indispensable step for preparation of dried samples, may be responsible for some of the conformational anomalies in the images previously reported. We have studied several protocols to observe supercoiled DNA molecules by SFM and discuss the merits and the demerits. Images obtained following uranyl acetate treatment may be ideal for the detection of DNA damage, as the supercoiled and nicked forms are easily distinguishable. PMID- 11779109 TI - Use of optical biosensor technology to study immunological cross-reactivity between different sulfonamide drugs. AB - Adverse reactions to medications account for a substantial number of hospitalizations and in some cases fatalities. The nature of the many drug-drug interactions caused by the inhibition of drug-metabolizing enzymes can now be predicted and examined with a greater deal of accuracy due to research developments in the understanding of the drug-metabolizing enzymes. However, the more troubling aspects of drug-drug interactions are the idiosyncratic reactions that are unpredictable and quite often life-threatening. These reactions are often caused by a prior sensitization of a person's immune system to a given drug or class of drugs. The following work offers a technique to examine in a medium throughput system the cross-reactivity of drugs to antibodies in order to predict if structures share the same antigenic potential toward a sensitized individual. Two commercially important sulfonamide drugs, sulfamethazine and furosemide, were taken and their binding to their respective antibodies were tested in the presence of other structurally related sulfonamide drugs. The BIACORE 3000 biosensor was used for the study and the solution-phase equilibrium assay principle was employed. The data obtained help us determine which drugs can react, and to what extent, with sulfamethazine and furosemide, giving rise to possible allergic or hypersensitivity reactions. Though sulfamethazine and furosemide were used in this study; this principle and methodology can be applied to study any drug molecule-antibody pair. PMID- 11779110 TI - A two-plasmid system for independent genetic manipulation of subunits of homodimeric proteins and selective isolation of chimeric dimers. AB - We have designed and tested a modular two-plasmid expression system which allows coexpression of two different subunits of recombinant dimeric protein in Escherichia coli and selective purification of heterodimers. We have constructed a new expression vector, pBIOEx, with p15a replication origin which allows its stable coexistence with different ColE1 group plasmids. The expression cassette of this plasmid under control of the T7 promoter contains cloning site, followed by a short sequence coding for the C-terminal extension of the recombinant protein which is a target of the in vivo biotinylation by BirA protein. The expression unit is bicistronic, the second expressed protein being BirA. We have used this plasmid together with pET30a to clone kinesin heavy-chain fragment and coexpressed the two polypeptide chains differing by tags on their C-termini and we purified heterodimers made of two recombinant molecules. The heterodimeric protein had a normal biochemical activity. There was no discrimination against heterodimer formation at the dimerization step. The system is a powerful tool in studies of different aspects of interactions between subunits of the homodimeric proteins since it makes possible separate genetic manipulations on each subunit of the dimer. PMID- 11779111 TI - 13C isotopomer analysis of glutamate by tandem mass spectrometry. AB - Tandem mass spectrometry allows a compound to be isolated from the rest of the sample and dissociated into smaller fragments. We show here that fragmentation of glutamate mass isotopomers yields additional mass spectral data that significantly improve the analysis of metabolic fluxes compared to full-scan mass spectrometry. In order to validate the technique, tandem and full-scan mass spectrometry were used along with (13)C NMR to analyze glutamate from rat hearts perfused with three substrate mixtures (5 mM glucose plus 5 mM [2-(13)C]acetate, 5 mM [1-(13)C]glucose plus 5 U/L insulin, and 5 mM glucose plus 1 mM [3 (13)C]pyruvate). Analysis by tandem mass spectrometry showed that the enriched substrate contributed 98 +/- 2, 53 +/- 2, and 84 +/- 7%, respectively, of acetyl coenzyme A while the rate of anaplerotic substrate entry was 7 +/- 3, 25 +/- 8, and 16 +/- 8%. Similar results were obtained with (13)C NMR data, while values from full-scan data had higher error. We believe that this is the first use of tandem mass spectrometry to determine pathway flux using (13)C-enriched substrates. Although analysis of the citric acid cycle by NMR is simpler (and more intuitive), tandem mass spectrometry has the potential to combine high sensitivity with the high information yield previously available only by NMR. PMID- 11779112 TI - Characterization of the metal-binding site of bovine growth hormone through site specific metal-catalyzed oxidation and high-performance liquid chromatography tandem mass spectrometry. AB - Metal-catalyzed oxidation was used to identify metal-binding His residues in bovine growth hormone (bGH), which has not been characterized well crystallographically due to a high propensity of bGH to aggregate. bGH was exposed to Cu(2+) and ascorbate (ascorbate/Cu(2+)/O(2)). 2-Oxo-His formation was identified by HPLC-tandem mass spectrometry (MS/MS) analysis of a tryptic digest. Two 2-oxo-His-containing fragments were detected, T2(O) (MH(2+)(2) = 748.8) and T20(O) (MH(+) = 528.3), both masses corresponding to the addition of only one oxygen atom (+16 amu) to the respective native fragments, T2 and T20. T2 contains (20)His and (22)His, and T20 contains (170)His. Quantitative HPLC-MS/MS analysis shows the following order of reactivity: (170)His >> (22)His > (20)His. Solvent accessible surface area calculations determined (22)His and (170)His to be 26 and 35% solvent exposed, respectively, while (20)His is 65% solvent exposed. The presence of an analogous metal-binding site in human growth hormone, which is located in the hydrophobic core, and our experimental finding that oxidation was greatest for (22)His and (170)His in bGH suggests that (22)His and (170)His of bGH participate in metal binding. This result is supported by a previously predicted tertiary structure of bGH and compared with the location of metal binding His residues of human growth hormone. PMID- 11779113 TI - Engineering a V(2) vasopressin receptor agonist- and regulator of G-protein signaling-sensitive G protein. AB - It is extremely difficult to detect guanine nucleotide exchange or hydrolysis stimulated by receptors which couple to G(s)alpha. Furthermore, G(s)alpha is largely resistant to the GTPase-activating properties of RGS proteins. Coexpression of the vasopressin V(2) receptor with a series of chimeric G protein alpha subunits in which the C-terminal 6-12 amino acids of G(i1)alpha were replaced with the equivalent sequence of G(s)alpha allowed robust vasopressin stimulated [(35)S]GTPgammaS binding. Vasopressin did not stimulate the GTPase activity of fusion proteins between the V(2) receptor and either G(s)alpha or G(i1)alpha. However, it produced a concentration-dependent stimulation of V(max) for a V(2) receptor-G(i1)alpha/Gs6alpha fusion protein. This construct bound [(3)H]vasopressin with high affinity and this was competed by other ligands with rank order anticipated for the V(2) receptor. RGS1 enhanced vasopressin stimulation of V(2) receptor-G(i1)alpha/G(s)6alpha in a concentration-dependent manner. RGS-GAIP was substantially less potent. Enzyme kinetic analysis demonstrated that RGS1 increased both V(max) of the GTPase activity and the observed K(m) for GTP, consistent with RGS1 accelerating the rate of GTP hydrolysis of the chimeric G protein, whereas the agonist vasopressin accelerates guanine nucleotide exchange. This approach provides a sensitive assay for V(2) receptor agonist ligands and may be amenable to many other G(s)alpha-coupled receptors. PMID- 11779114 TI - Problems associated with the identification of proteins in homologous families: the wool keratin family as a case study. AB - The keratin proteins from wool can be divided into two classes: the intermediate filament proteins (IFPs) and the matrix proteins. Using peptide mass spectral fingerprinting it was possible to match spots to the known theoretical sequences of some IFPs in web-based databases, as enzyme digestion generated sufficient numbers of peptides from each spot to achieve this. In contrast, it was more difficult to obtain good matches for some of the lower molecular weight matrix proteins. Relatively few peaks were generated from tryptic digests of high-sulfur proteins because of their lower molecular weight and the absence of basic residues in the first two-thirds of the sequence. Their high sequence homology also means that generally only a few of these peptides could be considered to be unique identifiers for each protein. Nevertheless, it was still possible to uniquely identify some of these proteins, while the presence of two peptides in the matrix-assisted laser desorption/ionization time-of-flight mass spectrum allowed classification of other protein spots as being members of this family. Only one major peptide peak was generated by the high-glycine tyrosine proteins (HGTPs) and there were relatively few sequences available in web-based databases, limiting their identification to one HGTP family. PMID- 11779115 TI - A fluorescence polarization assay for the identification of inhibitors of the p53 DM2 protein-protein interaction. AB - Improper function of the tumor suppressor protein p53 is a contributing factor in many human cancers. In normal cells, p53 acts to arrest the cell cycle in response to DNA damage or nucleotide depletion. One mechanism of regulating the amount of p53 in the cell is through the action of the Double Minute 2 protein, DM2 (also known as MDM2), which ubiquitinates p53 and targets it for proteosomal degradation. In a number of human cancers, the DM2 gene is amplified or overexpressed, leading to inadequate levels of p53 for cell cycle arrest or apoptosis. With the goal of restoring p53 function in cancers that overexpress DM2, we are developing inhibitors of the p53-DM2 protein-protein interaction that structurally mimic the N-terminal segment of p53 that binds to DM2. To assist this effort, we have devised a fluorescence polarization assay that quantifies the interaction between the N-terminal regions of both proteins in 384-well microtiter plates. Using this assay, we have demonstrated that a peptide with a nonhydrolyzable beta-amino acid substitution binds DM2 with an affinity comparable to a p53 peptide that is composed of only alpha-amino acids. PMID- 11779116 TI - A whole genome amplification method to generate long fragments from low quantities of genomic DNA. AB - Several whole genome amplification strategies have been developed to preamplify the entire genome from minimal amounts of DNA for subsequent molecular genetic analysis. However, none of these techniques has proven to amplify long products from very low (nanogram or picogram) quantities of genomic DNA. Here we report a new whole genome amplification protocol using a degenerate primer (DOP-PCR) that generates products up to about 10 kb in length from less than 1 ng genomic template DNA. This new protocol (LL-DOP-PCR) allows in the subsequent PCR the specific amplification, with high fidelity, of DNA fragments that are more than 1 kb in length. LL-DOP-PCR provides significantly better coverage for microsatellites and unique sequences in comparison to a conventional DOP-PCR method. PMID- 11779117 TI - A fluorometric assay for detection of lysyl oxidase enzyme activity in biological samples. AB - Lysyl oxidase catalyzes the final known enzymatic step required for collagen and elastin cross-linking in the biosynthesis of normal mature functional insoluble extracellular matrices. In addition, lysyl oxidase has been identified as a possible tumor suppressor. Lysyl oxidase activity in biological samples is traditionally and most reliably assessed by tritium release end-point assays using radiolabeled collagen or elastin substrates involving laborious vacuum distillation of the released tritiated water. In addition, a less sensitive fluorometric method exists that employs nonpeptidyl amine lysyl oxidase substrates and measures hydrogen peroxide production with horseradish peroxidase coupled to homovanillate oxidation. The present study describes a more sensitive fluorescent assay for lysyl oxidase activity that utilizes 1,5-diaminopentane as substrate, and released hydrogen peroxide is detected using Amplex red in horseradish peroxidase-coupled reactions. This method allows the detection of 40 ng of enzyme per 2 ml assay at 37 degrees C and is 7.5 times more sensitive than the currently available fluorometric assay for enzyme activity. This method eliminates the interference that occurs in some biological samples and can be successfully used to detect lysyl oxidase activity in cell culture experiments. PMID- 11779118 TI - Artifact-free quantification of free 3-chlorotyrosine, 3-bromotyrosine, and 3 nitrotyrosine in human plasma by electron capture-negative chemical ionization gas chromatography mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry. AB - Halogenation and nitration of biomolecules have been proposed as key mechanisms of host defense against bacteria, fungi, and viruses. Reactive oxidants also have the potential to damage host tissue, and they have been implicated in disease. In the current studies, we describe specific, sensitive, and quantitative methods for detecting three stable markers of oxidative damage: 3-chlorotyrosine, 3 bromotyrosine, and 3-nitrotyrosine. Our results indicate that electron capture negative chemical ionization-gas chromatography/mass spectrometry (EC-NCI GC/MS) is 100-fold more sensitive than liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) for analyzing authentic 3-chlorotyrosine, 3 bromotyrosine, and 3-nitrotyrosine. Using an isotopomer of tyrosine to evaluate artifactual production of the analytes during sample preparation and analysis, we found that artifact generation was negligible with either technique. However, LC MS/MS proved cumbersome for analyzing multiple samples because it required 1.5 h of run and equilibration time per analysis. In contrast, EC-NCI GC/MS required only 5 min of run time per analysis. Using EC-NCI GC/MS, we were able to detect and quantify attomole levels of free 3-chlorotyrosine, 3-bromotyrosine, and 3 nitrotyrosine in human plasma. Our results indicate that EC-NCI GC/MS is a sensitive and specific method for quantifying free 3-chlorotyrosine, 3 bromotyrosine, and 3-nitrotyrosine in biological fluids in a single, rapid analysis and that it avoids generating any of the analytes ex vivo. PMID- 11779119 TI - An improved fluorometric high-performance liquid chromatography method for sialic acid determination: an internal standard method and its application to sialic acid analysis of human apolipoprotein E. AB - An improved fluorometric HPLC method for sialic acid determination was developed by employing synthetic N-propionylneuraminic acid (NPNA) as an internal standard. A fixed amount of NPNA was added to a sialoglycoconjugate sample. After hydrolyzing sialioglycoconjugates with diluted sulfuric acid, the released sialic acids and NPNA were derivatized with a fluorogenic compound, 1,2-diamino-4,5 (methylenedioxy)benzene (DMB), followed by fluorometric HPLC. The fluorescent derivative of NPNA was separated from those of N-acetylneuraminic acid, N glycolylneuraminic acid, 2-keto-3-deoxy-D-glycero-D-galacto-nonoic acid, and 2 keto-3-deoxyoctanoate on HPLC. The separation of NPNA derivative on HPLC was not interfered by components of biological samples such as human sera. Using this internal standard method, low amounts of NANA (0.15-1.0 ng) were quantified with the coefficient of variation values below 4%. Using this method, the sialic acid content of human apolipoprotein E was successfully determined. The present method is useful for sensitive and accurate quantification of sialic acids of different molecular species in biological samples. PMID- 11779120 TI - Enzymatic synthesis of [5-(14)C]ribose. PMID- 11779121 TI - Quantitative reverse transcription-polymerase chain reaction (RT-PCR): a comparison of primer-dropping, competitive, and real-time RT-PCRs. PMID- 11779122 TI - Utility of single-strand conformation polymorphism analysis was improved by low cross-linking polyacrylamide gel and quick low-background silver staining. PMID- 11779123 TI - A continuous fluorometric assay of myristoyl-coenzyme A:protein N myristoyltransferase. PMID- 11779124 TI - Molecular regulation of muscle cachexia: it may be more than the proteasome. AB - Muscle cachexia induced by sepsis, severe injury, cancer, and a number of other catabolic conditions is mainly caused by increased protein degradation, in particular breakdown of myofibrillar proteins. Ubiquitin-proteasome-dependent proteolysis is the predominant mechanism of muscle protein loss in these conditions, but there is evidence that several other regulatory mechanisms may be important as well. Some of those mechanisms are reviewed in this article and they include pre-, para-, and postproteasomal mechanisms. Among preproteasomal mechanisms, mediators, receptor binding, signaling pathways, activation of transcription factors, and modification of proteins are important. Several paraproteasomal mechanisms may influence the trafficking of ubiquitinated proteins and their interaction with the proteasome, including the expression and activity of the COP9 signalosome, the carboxy terminus of heat shock protein 70 interacting protein (CHIP) and valosin-containing protein (VCP). Finally, because the proteasome does not degrade proteins completely into free amino acids but into peptides, postproteasomal degradation of peptides by the giant protease tripeptidyl peptidase II (TPP II) and various aminopeptidases is important in muscle catabolism. Thus, multiple mechanisms and regulatory steps may influence the breakdown of ubiquitinated muscle proteins by the 26S proteasome. PMID- 11779125 TI - c-myc Suppression in Burkitt's lymphoma cells. AB - The purpose of the study was to elucidate how DNA tetraplex (also referred to as G-quadruplex)-forming oligonucleotides mediate suppression of the human c-myc gene at the level of transcription initiation. A 22-base-long oligonucleotide, which is rich in guanines and folds into an intrastrand DNA tetraplex under physiological conditions, was administered to a Burkitt's lymphoma cell line overexpressing a (8:14) translocated c-myc allele. Administration of the oligonucleotide at nanomolar concentrations to the surrounding medium resulted in efficient cellular uptake, and was accompanied by a substantial concentration- and conformation-dependent decrease in growth rate. We discuss how c-myc transcription is initiated at the molecular level and speculate that the oligonucleotide exerts a dual effect on c-myc expression in vivo. PMID- 11779126 TI - Mononucleosomes assembled on a DNA fragment containing (GGA/TCC)(n) repeats can form a DNA-DNA complex. AB - A DNA fragment of 163 bp containing 11 GGA repeats formed two-end positioned mononucleosomes as efficiently as that of CTG repeats. However, the rotational positioning of the GGA fragment was weak because clear DNase I cleavage patterns with 10-base periodicity were not seen near the center of the GGA fragment but were detected in the entire region of the CTG fragment. Incubation of the GGA mononucleosomes with the same fragment provided the DNA-DNA complex, which had been shown by using naked DNA fragments. DNase I digestion of the complex exhibited protection in the GGA repeats and in flanking sequences of about 30 bp at both sides, suggesting that both the repeat and flanking regions were involved in the association. Interestingly, histone H1, which enhanced DNA-DNA association on naked DNA, did not affect the complex formation on mononucleosomes. These results imply that GGA microsatellites in genomes could associate with one another at multiple sites and that the association may play a role in functional organization of higher order chromatin architecture. PMID- 11779127 TI - Fluorescence imaging of metabolic responses in single mitochondria. AB - The membrane potentials, rates of NAD(P)H formation, and rates of flavoprotein reduction have been measured for single mitochondria isolated from porcine hearts. These metabolic responses were elicited by the addition of malate and measured using fluorescence microscopy. For the measurements of mitochondrial membrane potential, mitochondria were stained with tetramethylrhodamine ethyl ester, and the membrane potentials of single mitochondria were determined. Individual mitochondria maintained the membrane potential at around -80 mV before addition of malate. Upon the addition of malate, each mitochondrion was rapidly polarized to around -100 approximately -140 mV and underwent repeated cycles of polarization and depolarization, which were probably caused by openings and closings of permeability transition pores. NAD(P)(+) and flavoprotein were reduced immediately after addition of malate and then slowly became reoxidized. Thus, single mitochondria can undergo rapid and repetitive changes in membrane potential, but not in the redox state of NAD(P)H and flavoprotein. PMID- 11779128 TI - Trypanosoma cruzi uses a 45-kDa mucin for adhesion to mammalian cells. AB - A set of monoclonal antibodies that recognizes a Trypanosoma cruzi 45-kDa protein was produced and used to characterize this molecule and study its role in trypanosome adhesion to heart myoblasts. We found that the 45-kDa protein is a surface mucin, is expressed only in invasive trypomastigotes, but not in noninvasive epimastigotes or amastigotes, and is released by the trypanosome in culture medium. One of the monoclonal antibodies (Mab B5) from this set inhibits the attachment of trypomastigotes to heart myoblasts preventing trypanosome entry, whereas the others (Mabs B4 and F1) do not. This inhibition was seen with the B5 hybridoma culture supernatant, with the purified Mab B5 IgG or with Mab B5 Fab fragments. These novel findings identify the 45-kDa mucin as a new T. cruzi ligand that is used by invasive forms of this organism to adhere to heart myoblasts. PMID- 11779129 TI - AP180 binds to the C-terminal SH2 domain of phospholipase C-gamma1 and inhibits its enzymatic activity. AB - The role of phospholipase Cgamma1 (PLCgamma1) in signal transduction was investigated by characterizing its SH domain-binding proteins that may represent components of a novel signaling pathway. A 180-kDa protein that binds to the SH2 domain of PLCgamma1 was purified from rat brain. The amino acid sequence of peptide derived from the purified protein is now identified as AP180, a clathrin assembly protein that has been implicated in clathrin-mediated synaptic vesicle recycling in synapses. In this report, we demonstrate the stable association of PLCgamma1 with AP180 in a clathrin-coated vesicle complex, which not only binds to the carboxyl-terminal SH2 domain of PLCgamma1, but also inhibits its enzymatic activity in a dose-dependent manner. PMID- 11779131 TI - Direct antioxidant properties of creatine. AB - Creatine is the most popular supplement proposed to be an ergogenic aid. There is some evidence in the literature that creatine supplementation increases lean body mass, muscular strength, and sprint power. However, the efficacy of creatine has not been consistent, and the potential mechanisms are unresolved. While limited evidence that suggests that creatine could possess an antioxidant effect this has not been tested directly. Because oxidants such as free radicals can affect muscle fatigue and protein turnover, it is important to know whether creatine can neutralize free radicals and other reactive oxygen species. We tested the hypothesis that creatine would remove superoxide anions (O(*-)(2)), peroxynitrite (OONO-), hydrogen peroxide, and lipid peroxides (t-butyl hydroperoxide). We also determined whether creatine displayed a significant antioxidant scavenging capacity (ASC) using 2,2'-azino-bis(3-ethylbenzothiazolamine-6-sulfonic acid) (ABTS+) quenching as a marker. Creatine did not significantly reduce levels of hydrogen peroxide or lipid peroxidation. In contrast, creatine displayed a significant ability to remove ABTS+, O(*-)(2), and OONO- when compared with controls. Creatine quenching of ABTS+ was less than physiological levels of reduced glutathione (0.375 mM). To our knowledge, this is the first evidence that creatine has the potential to act as a direct antioxidant against aqueous radical and reactive species ions. PMID- 11779130 TI - Protein Kinase C is a mediator of the synthesis and secretion of osteoprotegerin in osteoblast-like cells. AB - Osteoprotegerin (OPG) is a member of the TNF receptor superfamily and plays a critical role in the development of osteoclasts from precursor cells. OPG is produced by a variety of cells of mesenchymal origin and has been demonstrated to be present in osteoblasts and osteocytes. However, the mechanisms of regulation of OPG production and secretion are not known. Using a highly specific polyclonal antibody, we demonstrate that OPG is synthesized and secreted by osteoblast-like cells in culture. We further show that phorbol myristate acetate, an activator of protein kinase C, activated the secretion of OPG. Further, the increased secretion of OPG correlated well with a corresponding increase in OPG mRNA abundance. In addition, OPG promoter stably integrated into an osteoblast cell line was activated by phorbol myristate acetate. The increase in OPG expression was blocked by an inhibitor of protein kinase C, although the basal OPG expression was not altered. These results suggest that activation of the protein kinase C pathway may play a critical role in OPG expression. PMID- 11779132 TI - Effect of the rabbit alphas1-casein gene distal enhancer on the expression of a reporter gene in vitro and in vivo. AB - Several gene constructs containing the firefly luciferase gene and the herpes simplex virus thymidine kinase gene promoter (TK) were used to evaluate the transcriptional activity of the distal enhancer (-3442, -3285) of the rabbit alphas1-casein gene. Six copies of the enhancer (6i) were added upstream of the TK-luciferase construct in the presence or absence of the chicken beta-globin 5'HS4 insulator. The activity of the constructs was tested by transient transfection in CHO cells and in rabbit primary mammary cell cultured on plastic or on floating collagen. Constructs were also tested in stably transfected mouse mammary HC11 cells. In all cell types the multimerized alphas1-casein enhancer strongly stimulated luciferase gene expression in the presence of lactogenic hormones. It was also sensitive to the extracellular matrix in rabbit primary mammary cells. The constructs were used to generate transgenic mice. The 6i TK transgenic animals expressed the luciferase gene at very low levels irrespectively of the physiological state. No preferential expression in the mammary gland was observed. Addition of 5'HS4 insulator to the 6i TK construct did not prevent silencing in most of the transgenic lines. However, two lines expressed high luciferase levels specifically in the mammary gland. Our data suggest that 6i may confer, when insulated properly, a higher and mammary specific expression to the TK promoter. PMID- 11779133 TI - Purification and characterization of methionine sulfoxide reductases from mouse and Staphylococcus aureus and their substrate stereospecificity. AB - Many organisms have been shown to possess a methionine sulfoxide reductase (MsrA), exhibiting high specificity for reduction the S form of free and protein bound methionine sulfoxide to methionine. Recently, a different form of the reductase (referred to as MsrB) has been detected in several organisms. We show here that MsrB is a selenoprotein that exhibits high specificity for reduction of the R forms of free and protein-bound methionine sulfoxide. The enzyme was partially purified from mouse liver and a derivative of the mouse MsrB gene, in which the codon specifying selenocystein incorporation was replaced by the cystein codon, was prepared, cloned, and overexpressed in Escherichia coli. The properties of the modified MsrB protein were compared directly with those of MsrA. Also, we have shown that in Staphylococcus aureus there are two MsrA and one nonselenoprotein MsrB, which demonstrates the same substrate stereospecificity as the mouse MsrB. PMID- 11779134 TI - Analysis of the gene expression profiles of immature versus mature bone marrow derived dendritic cells using DNA arrays. AB - Dendritic cells (DCs) are professional antigen-presenting cells of the immune system and can be generated in vitro from bone-marrow cells. In this study, we systematically investigated by DNA array analysis the expression profiles of 514 immunologically relevant genes in two populations of mouse bone marrow-derived DC, immature (DC(IMAT)), and lipopolysaccharide (LPS)-stimulated mature (DC(MAT)) DCs. Our data showed that DC(IMAT) expressed transcripts for 69 (13.42% of the 514) of these genes and that, upon maturation, 32 (6.23%) of these were up regulated and 40 (7.78%) down-regulated. Maturation-dependent up-regulation, defined by a differential expression (DE) ratio of >2, was observed among five cytokine (Flt-3L, TNF-alpha, IL-1alpha and -1beta, and IL-6), three chemokine (RANTES, MIP-2 and GROa) and three other (iNOS, MMP-13, and STRAP) genes. Reciprocally, maturation-dependent down-regulation occurred with one cytokine (IGF-1), two chemokine receptor (CCR2 and CCR5), and three other (RP105, Ax1, and UCP2) genes. Lower level, but nevertheless significantly enhanced expression of the chemokine receptor CCR7 and of NF-kappaB was also observed upon DC maturation. This DC maturation profile confirms previous findings from other lab, but it also substantially broadens our view of these cells by documenting expression changes among genes (e.g., IGF-1, MMP-13, STRAP) not reported previously in these cells. PMID- 11779135 TI - Differential expression of the isoforms for the monocyte chemoattractant protein 1 receptor, CCR2, in monocytes. AB - Two isoforms of human CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), have been identified but their relative expression in monocytes and contribution to inflammatory responses mediated by MCP-1 remain uncertain. All available information on CCR2 expression is based on mRNA data because isoform specific antibodies were not available until now. To analyze the relative expression of each isoform, we made two antibodies that specifically recognized CCR2A and CCR2B. Examination of receptor protein with these isoform-specific antibodies showed that the total expression of CCR2B in monocytes was about 10 fold higher than that of CCR2A with an equal distribution between the cell surface and intracellular pools. A detailed analysis using purified plasma membranes demonstrated that about 90% of all CCR2 on the cell surface were composed of CCR2B. The relatively abundant expression of CCR2B on the cell surface suggests a principal role of this isoform as a mediator of monocyte responses to MCP-1 in inflammation. PMID- 11779136 TI - Base frequencies at the second codon position of Vibrio cholerae genes connect with protein function. AB - In this paper, the base frequency at the second codon position of the 3839 open reading frames (ORFs) in the Vibrio cholerae genome is analyzed. It is shown that according to the base content at this codon site, the ORFs can be divided into two clusters, each containing 673 and 3166 ORFs, respectively. ORFs in the smaller cluster usually have significantly higher T frequency than that of A at the second codon position. For the two clusters of ORFs, there are significant differences in the frequencies for 18 of the 20 amino acids in the encoding proteins. The two clusters of ORFs are also significantly different in their functions. More than half of the known genes involved in transport and binding are included in the smaller cluster, while few genes involved in amino acid biosynthesis, protein synthesis, and so on are included in this cluster. PMID- 11779137 TI - PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046-38. AB - Protein kinase C seems to be linked to the regulation of insulin secretion as well as mitogenic signaling in pancreatic beta cells. To study the impact of different PKC isoforms on insulin secretion and mitogenic activity we stably overexpressed the PKC isoforms alpha, beta2, epsilon, and zeta in the rat clonal beta cell line RIN 1046-38. Under basal conditions PKC alpha, beta2, epsilon, and zeta were identified mainly in the cytosol. Treatment with the phorbol ester TPA caused translocation of PKC alpha, beta2, and epsilon to the plasma membrane. Glucose- and TPA-dependent increases in insulin release were comparable in all cell lines regardless of whether PKC was overexpressed or not. While PKC isoforms alpha, beta2, and epsilon had no effect on the [(3)H]thymidine incorporation rate, overexpression of PKC zeta specifically increased basal as well as IGF-1 dependent [(3)H]thymidine incorporation. Incubation with the MAP-kinase inhibitor PD98056 abolished this effect. Furthermore, treatment with IGF-1 led to activation of the beta cell-specific transcription factor PDX-1 in RIN 1046-38 cells overexpressing PKC zeta. Our data suggest that PKC zeta is involved in basal as well as IGF-1-dependent mitogenesis in RIN 1046-38 cells, while none of the PKC isoforms tested seem to be related to glucose-stimulated insulin release. PMID- 11779138 TI - Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF beta. AB - The marijuana-derived cannabinoid Delta(9)-tetrahydrocannabinol (THC) has been shown to be immunosuppressive. We report that THC induces the immunosuppressive cytokine TGF-beta by human peripheral blood lymphocytes (PBL). The ability of THC to stimulate TGF-beta production was blocked by the CB2 receptor specific antagonist SR144528 but not by the CB1 specific antagonist AM251. Furthermore, our data suggest that TGF-beta actively regulates lymphocyte CB2 receptor expression in an autocrine and paracrine manner. Whereas the addition of recombinant TGF-beta to PBL cultures downregulated CB2 receptor expression, anti TGF-beta antibody treatment increased CB2 receptor expression. We conclude that one mechanism by which THC contributes to immune suppression is by stimulating an enhanced production of lymphocyte TGF-beta. PMID- 11779139 TI - NO synthesis, unlike respiration, influences intracellular oxygen tension. AB - We have developed a new phosphorescent probe, PdTCPPNa(4), whose luminescence properties are affected by local variations of intracellular oxygen tension (PO(2)). Spectrofluorometric measurements on living human umbilical venous endothelial cells loaded with this molecule show that a decrease in extracellular oxygen tension induces a decrease of PO(2), illustrating the phenomenon of oxygen diffusion and validating the use of this probe in living cells. Moreover, KCN- or 2,4-dinitrophenol-induced modifications of respiration do not lead to detectable PO(2) variations, probably because O(2) diffusion is sufficient to allow oxygen supply. On the contrary, activation by acetylcholine or endothelial nitric oxide synthase (eNOS), which produces NO while consuming oxygen, induces a significant decrease in PO(2), whose amplitude is dependent on the acetylcholine dose, i.e., the eNOS activity level. Hence, activated cytosolic enzymes could consume high levels of oxygen which cannot be supplied by diffusion, leading to PO(2) decrease. Other cell physiology mechanisms leading to PO(2) variations can now be studied in living cells with this probe. PMID- 11779140 TI - Domains I and II in the 5' nontranslated region of the HCV genome are required for RNA replication. AB - Hepatitis C virus (HCV), a hepacivirus member of the Flaviviridae family, has a positive-stranded RNA genome, which consists of a single open reading frame (ORF) and nontranslated regions (NTRs) at the 5' and 3' ends. The 5'NTR was found to contain an internal ribosomal entry site (IRES), which is required for the translation of HCV mRNA. Moreover, the 5'NTR is likely to play a key role in the replication of viral RNA. To identify the cis-acting element required for viral RNA replication, chimeric subgenomic replicons of HCV were generated. Dissection of the replication element from the translation element was accomplished by inserting the polioviral IRES between the serially deleted 5'NTR of HCV and ORF encoding neomycin phosphotransferase. The deletions of the 5'NTR of HCV were performed according to the secondary structure of HCV. Replicons containing domains I and II supported RNA replication and further deletion toward the 5' end abolished replication. The addition of domain III and the pseudoknot structure of the 5'NTR to domains I and II augmented the colony-forming efficiency of replicons by 100-fold. This indicates that domains I and II are necessary and sufficient for replication of RNA and that almost all of the 5'NTR is required for efficient RNA replication. PMID- 11779141 TI - FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology. AB - We have previously cloned the alternatively spliced isoform of fibroblast growth factor receptor 3 (FGFR3DeltaAB) that lacks the acid box in the extracellular region. To understand the biological functions and signal transduction of these FGFR3 isoforms, we analyzed the effect of FGF1 in ATDC5 cells, chondroprogenitor cell lines overexpressing these isoforms. In response to FGF1, FGFR3 induced a marked cell-morphology change to a round shape, while FGFR3DeltaAB did not. Furthermore, FGFR3 induced complete growth arrest, whereas FGFR3DeltaAB induced only moderate growth inhibition. Both receptors induced the expression of the CDK inhibitor p21(CIP1). However, only FGFR3 induced STAT1 phosphorylation that mediates the transcriptional induction of p21(CIP1), although both FGFR3 isoforms could induce a strong activation of mitogen-activated protein (MAP) kinases. Taken together, the different biological responses mediated by FGFR3 and FGFR3DeltaAB appear to be due to a difference in their ability to utilize STAT1 pathway and signals involved in cell rounding. PMID- 11779142 TI - Inhibitors of fibril formation and cytotoxicity of beta-amyloid peptide composed of KLVFF recognition element and flexible hydrophilic disrupting element. AB - Beta-Amyloid peptide (Abeta) is the main protein components of neuritic plaques and its neurotoxicity would be exposed by formation of aggregate. The aggregation inhibitors composed of an Abeta recognition element (KLVFF) and a flexible hydrophilic disrupting element (aminoethoxy ethoxy acetate and aspartate) are designed and chemically synthesized. The inhibitory effects are examined by a pigment binding assay using Congo red or thioflavin T. The present compounds suppress the formation of aggregate, and the compound DDX3 is an especially effective inhibitor. In addition, the synthesized compounds efficiently suppress the cytotoxicity of Abeta against IMR-32 neuroblastoma cells in vitro. PMID- 11779143 TI - NO-steroids: potent anti-inflammatory drugs with bronchodilating activity in vitro. AB - The synthesis of nitric oxide (NO) releasing anti-inflammatory molecules is an innovative strategy to design novel anti-inflammatory drugs. These compounds slowly release NO, via an enzymatic pathway conferring new biological activities. Here we report the potent anti-inflammatory profile and the bronchodilator effect of nitro-derivatives of steroids, prednisolone, especially. The experiments were performed on guinea pig trachea or perfused bronchioles precontracted by methacholine. We demonstrated for the first time that unlike the parent compounds which produced weak bronchodilation at the maximum used dose (10(-4) M), NO steroids caused a significant bronchodilating activity up to 70% of the maximal relaxation induced by 10(-4) M papaverine. This effect was epithelium- and endogenous-independent but cGMP-dependent. Taken together these data suggest that NO-steroids possessed a more potent anti-inflammatory activity than native compounds coupled with a concentration-dependent bronchodilating activity. Further studies are required to determine if NO-steroids will be effective as anti-inflammatory agents in the clinic. PMID- 11779144 TI - Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. AB - In this study, we used a coactivator-dependent receptor-ligand interaction assay (CARLA), which is a semifunctional in vitro assay, to determine whether hypolipidemic drugs are ligands for the three peroxisome proliferator-activated receptor isotypes (PPARalpha, delta, and gamma). We also evaluated the transcriptional activities of the three PPAR isotypes by transient transfection assays. We found that bezafibrate was a ligand for PPARalpha, delta, and gamma in the CARLA and that bezafibrate induced transcriptional activation of PPARalpha/RXRalpha, PPARdelta/RXRalpha, and PPARgamma/RXRalpha. Although the 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors cerivastatin, fluvastatin, and pitavastatin were not ligands for these three nuclear receptors in the CARLA, they induced transcriptional activation of PPARalpha/RXRalpha, PPARdelta/RXRalpha, and PPARgamma2/RXRalpha. Moreover, cerivastatin, fluvastatin, and pitavastatin synergistically and dose-dependently increased the transcriptional activation of PPARalpha/RXRalpha induced by bezafibrate. In addition, the cerivastatin-induced transcriptional activation of PPARalpha/RXRalpha was decreased by addition of mevalonate, farnesol, geranylgeraniol, or cholesterol and by co-transfection with sterol regulatory element-binding protein-1 (SREBP-1). Moreover, concomitant administration of statins and fibrates also decreased the transactivation of nuclear factor kappaB (NFkappaB) and the activation of NFkappaB by mitogen-activated protein kinase kinase kinase (MEKK) also decreased the transactivation of PPARalpha/RXRalpha. PMID- 11779145 TI - High levels of RAE-1 isoforms on mouse tumor cell lines assessed by anti-"pan" RAE-1 antibody confer tumor susceptibility to NK cells. AB - Two sublines of the benzpyrene-induced mouse hepatoma cell line, G-1 and G-5, showed low and high metastatic ability, respectively, to the lung. We produced a polyclonal antibody (pAb) against RAE-1alpha. Five isoforms of RAE-1 have been identified to date, and this pAb recognized all isoforms and was named anti-"pan" RAE-1 pAb. The level of RAE-1 was approximately 5-fold higher in G-5 than in G-1, which was almost RAE-1-negative, as determined using anti-pan RAE-1 pAb. Expression levels of other markers including MHC class I (MHC-I) and Qa-1b were very low and indistinguishable in these sublines. NK-mediated cytotoxicity was determined with these sublines; G-5 was highly susceptible to NK-mediated cytolysis, while G-1 was relatively resistant. The NK-mediated G-5 > G-1 killing profile was diminished if the G-5 cells were pretreated with F(ab)(2)(') of anti pan RAE-1 pAb. G-1, when transfected with Rae-1alpha cDNA, acquired NK responsiveness similar to that of G-5. These and additional data using mouse cell lines with low MHC-I levels and various RAE-1 levels also demonstrated that RAE-1 level is critically associated with NK-susceptibility in tumor cells. PMID- 11779146 TI - Expression and characterization of minican, a recombinant syndecan-1 with extensively truncated core protein. AB - Syndecan-1 is an integral membrane heparan sulfate/chondroitin sulfate proteoglycan, involved in the control of cell growth and differentiation. The biological activities of syndecan-1 involve interactions with a variety of extracellular ligands, such as growth factors and matrix components, that are mainly mediated by the heparan sulfate moieties. The expression of syndecan-1 is downregulated in various malignant tumors, and low levels of expression appear to correlate with poor prognosis of some cancer types. On the other hand, the extracellular portion of syndecan-1 (ectodomain) has been demonstrated to inhibit the proliferation of various cancer cells in culture, suggesting that proteoglycan-like molecules should be studied further with regard to their antitumor activities. We have expressed, in CHO cells, a truncated syndecan-1 ectodomain ("minican") harboring domains for glycosaminoglycan attachment and antibody recognition. Analysis of recombinant minican indicates that it shares some of the biochemical and biological characteristics attributed to syndecan-1 ectodomain. Minican was thus substituted with heparan sulfate chains and bound to extracellular matrix proteins as well as fibroblast growth factors. Notably, minican inhibited the proliferation of S115 mouse mammary carcinoma cells and the effect seemed to involve inhibition of the Ras/Erk signaling pathway. Our data suggest that recombinant syndecan-1 with a minimal protein component is biologically active. This information may provide useful in further design of proteoglycan-like antitumor molecules. PMID- 11779147 TI - Side chain modifications change the binding and agonist properties of endomorphin 2. AB - Side chain modifications were introduced to endomorphin 2 (E2) to improve its binding properties and biological activity. A number of C-terminal modifications decreased the binding affinity to the mu-opioid receptor and the intrinsic activity in rat brain membranes. The exception was E2-ol, which showed increased binding affinity to MOR and higher potency in stimulating [(35)S]GTPgammaS binding. N-methylation of Phe(3) (MePhe(3)) attenuated the binding affinity and produced a rightward shift of [(35)S]GTPgammaS binding curves. All derivatives had lower intrinsic activity than E2. Some of the modified peptides partially inhibited, while YPF-benzyl-allyl-amide fully inhibited, the E2 or [d Ala(2),MePhe(4),Gly(5)ol]enkephalin stimulated [(35)S]GTPgammaS binding. Marked differences were found between the results obtained using tritiated E2, tritiated naloxone, and [(35)S]GTPgammaS binding, indicating the possible involvement of multiple binding sites. The data presented demonstrate that the C-terminal amide group has an essential role in the regulation of the binding and the agonist/antagonist properties of E2. PMID- 11779148 TI - Augmentation of receptor-mediated adenylyl cyclase activity by Gi-coupled prostaglandin receptor subtype EP3 in a Gbetagamma subunit-independent manner. AB - We previously demonstrated that the mouse EP3beta receptor and its C-terminal tail-truncated receptor (abbreviated T-335) expressed in Chinese hamster ovary cells showed agonist-dependent and fully constitutive Gi activity in forskolin stimulated cAMP accumulation, respectively. Here we examined the effect of the EP3beta receptor or T-335 receptor on adenylyl cyclase activity stimulated by the Gs-coupled EP2 subtype receptor in COS-7 cells. As a result, sulprostone, a selective EP3 agonist, dose dependently augmented butaprost-stimulated adenylyl cyclase activity in EP3beta receptor- or T-335 receptor-expressing COS-7 cells. However, such adenylyl cyclase augmentation was not attenuated by either pertussis toxin treatment or expression of the PH domain of rat betaARK1, which serves as a scavenger of Gbetagamma subunits, but was partially attenuated by treatment with either 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester, an intracellular Ca(2+) chelator, or W-7, a calmodulin inhibitor. These findings suggest that the C-terminal tail of the EP3beta receptor is not essentially involved in activation of EP2 receptor-stimulated adenylyl cyclase in a Ca(2+)/calmodulin-dependent but Gbetagamma subunit independent manner. PMID- 11779149 TI - Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation. AB - Fibroblast growth factor (FGF) 5 inhibits hair growth and induces catagen in mouse hair follicles, in vivo. Given that FGF-5 receptor (FGFR1) is expressed in dermal papilla cells (DPCs), which are known to stimulate outer root sheath cell (ORSC) proliferation, we hypothesized that FGF-5 attenuates DPC-mediated ORSC proliferation. In the present study, DPCs and ORSCs were isolated from rat vibrissae, after which the effects of FGF-5 on proliferation of ORSCs cultured in DPC-conditioned medium were assessed. We first confirmed that FGFR1 was expressed in cultured DPCs and detected FGFR2-4 as well. ORSC proliferation was increased approximately twofold when the cells were cultured in DPC-conditioned medium, and the effect was unaltered by FGF-5. In addition, FGF-5 did not directly inhibit ORSC proliferation; indeed, it actually promoted proliferation of both DPCs and ORSCs. When DPCs were first activated by exposure to FGF-1 and FGF-2, which are expressed in hair follicles during anagen, ORSC proliferation observed in the resultant conditioned medium was substantially greater than in medium conditioned by unstimulated DPCs. The FGF-1-induced enhancement was reversed by FGF-5, diminishing ORSC proliferation to control levels. By contrast, the enhancement of DPC-mediated ORSC proliferation by FGF-2 was not suppressed by FGF-5. Proliferation of ORSCs did not depend on DPC proliferation, nor did FGF-1 directly promote ORSC proliferation. Dermal papillae thus appear to require activation before they will efficiently stimulate hair growth, and FGF-5 appears to inhibit hair growth and induce catagen by blocking that activation. PMID- 11779150 TI - High glucose induced VEGF expression via PKC and ERK in glomerular podocytes. AB - Podocytes are the major site of vascular endothelial growth factor (VEGF) production in the kidney, and up-regulation of VEGF plays a critical role in the progression of diabetic nephropathy. Using a differentiated mouse podocyte cell line, we investigated the roles of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) on the expression of VEGF under high glucose conditions. High glucose induced up-regulation of VEGF mRNA and protein expression in podocytes via activation of PKC (PKC-alpha and -betaII isoforms) and ERK. High glucose stimulated [(3)H]leucine incorporation in the podocytes. High glucose and the PKC stimulator, phorbol 12-myristate 13-acetate (PMA) induced activator protein-1 (AP-1)-dependent transcriptional activity and expression of VEGF. In addition, these phenomena were blocked by specific inhibitors of PKC (GF10902X) and ERK kinase (PD98059). These observations suggested that high glucose-induced VEGF expression in podocytes was largely mediated through PKC and ERK pathways that may be involved in diabetic nephropathy. PMID- 11779151 TI - Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization. AB - Here we show that extracts of Boswellia serrata gum resins and its constituents, the boswellic acids (BAs), activate the mitogen-activated protein kinases (MAPK) p42(MAPK) and p38 in isolated human polymorphonuclear leukocytes (PMNL). MAPK activation was rapid and transient with maximal activation after 1-2.5 min of exposure and occurred in a dose-dependent manner. The keto-BAs (11-keto-beta-BA and 3-O-acetyl-11-beta-keto-BA) gave substantial kinase activation at 30 microM, whereas other BAs lacking the 11-keto group were less effective. Moreover, 11 keto-BAs induced rapid and prominent mobilization of free Ca(2+) in PMNL. Inhibitor studies revealed that phosphatidylinositol 3-kinase (PI 3-K) is involved in BA-induced MAPK activation, whereas a minor role was apparent for protein kinase C. MAPK activation by 3-O-acetyl-11-beta-keto-BA was partially inhibited when Ca(2+) was removed by chelation. Our results suggest that 11-keto BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Ca(2+). PMID- 11779152 TI - Insertion of dibasic residues directs a constitutive protein to the regulated secretory pathway. AB - The mechanisms for sorting proteins to the regulated secretory pathway (RSP) remains poorly understood. We recently reported that dibasic sequences that are cleaved by pro-protein convertases (PCs) in pro-neurotensin also acted as sorting signal for the precursor. Here we addressed two questions regarding the role of dibasics as sorting signal: (i) Are dibasics sufficient to direct proteins to the RSP? (ii) Do they sort proteins by virtue of their interaction with PCs? The first question was studied by inserting dibasics in beta-lactamase, a constitutively secreted protein and comparing the regulated secretion of beta lactamase to that of its mutant in transfected endocrine cells. The second question was investigated by comparing the regulated release of pro-neurotensin in PC12 cells that are devoid of PCs to that in PC1- and PC2-transfected PC12 cells. The data show that the mutant beta-lactamase was indeed targeted in part to the RSP and that pro-neurotensin was sorted to the RSP without the assistance of the PCs, thus indicating that dibasics can act as sorting signal by themselves independently of their interaction with PCs. PMID- 11779153 TI - Integral role of the EGF receptor in HGF-mediated hepatocyte proliferation. AB - Hepatocyte growth factor (HGF), insulin, and TGF-alpha stimulate DNA synthesis in cultured hepatocytes. Each ligand activates a distinct tyrosine kinase receptor, although receptor cross-talk modulates signaling. In rat hepatocytes, HGF can stimulate TGF-alpha production while TGF-alpha antibodies or antisense oligonucleotides suppress HGF-stimulated DNA synthesis. We report that the epidermal growth factor receptor (EGFR) kinase inhibitor PKI166 blocked both basal and ligand-induced tyrosine phosphorylation of the EGFR (IC(50) = 60 nM), but not of the insulin receptor or c-met. Pharmacologic inhibition of the EGFR kinase abolished the proliferative actions of HGF and EGF, but not insulin, whereas PI-3 kinase inhibition blocked both EGF and insulin actions. We conclude that in cultured hepatocytes (i) PI-3 kinase is required for EGF- and insulin induced proliferation and (ii) EGFR mediates both the basal rate of DNA synthesis and that induced by EGF and HGF, but not insulin. The mitogenic effect of HGF may be secondary to increased synthesis or processing of EGFR ligands such as TGF alpha. PMID- 11779154 TI - Structural studies of porcine myeloid antibacterial peptide PMAP-23 and its analogues in DPC micelles by NMR spectroscopy. AB - PMAP-23 is a cathelicidin-derived antimicrobial peptide identified from porcine leukocytes. PMAP-23 was reported to show potent antimicrobial activity against Gram-negative and Gram-positive bacteria without hemolytic activity. To study the structure-antibiotic activity relationships of PMAP-23, two analogues by replacing Trp with Ala were synthesized and their tertiary structures bound to DPC micelles have been studied by NMR spectroscopy. PMAP-23 has two alpha helices, one from Arg1 to Arg10 in the N-terminal region and the other from Phe18 to Arg23 in the C-terminal region. PMAP-1 (Trp(7)-->Ala) shows similar structure to PMAP-23, while PMAP-2 (Trp(21)-->Ala) has a random structure in the C terminus. PMAP-2 was found to show less antibacterial and vesicle-disrupting activities than PMAP-23 and PMAP-1 [J. H. Kang, S. Y. Shin, S. Y. Jang, K. L. Kim, and K.-S. Hahm (1999) Biochem. Biophys. Res. Commun. 264, 281-286]. Trp(21) in PMAP-23 which induces an alpha-helical structure in the second alpha-helix is essential for the antibacterial activity of PMAP-23. Also, the fluorescence data proved that Trp(21) at the second alpha-helix is buried deep into the phospholipid in the membrane. Therefore, it implies that Trp(21) in the second alpha-helix at the C-terminus of PMAP-23 may play an important role on the interactions with the membrane and the flexible region including two proline residues may allow this alpha-helix to span the lipid bilayer. PMID- 11779155 TI - Modulation of iron regulatory protein-1 by various metals. AB - Iron regulatory protein-1 (IRP-1) is known as a cytosolic aconitase and a central regulator of iron (Fe) homeostasis. IRP-1 regulates the expression of Fe metabolism-related proteins by interacting with the Fe-responsive element (IRE) in the untranslated regions of mRNAs of these proteins. However, it is less known whether IRP-1 modulates various non-Fe metals. In the present study, we showed that treatment of homogenously purified IRP-1 with non-Fe metals decreased the affinity to IRE in RNA band shift assays and increased aconitase activity. Non-Fe metals also inhibited (55)Fe incorporation into the fourth labile position of the Fe-S cluster of IRP-1. In PLC hepatoma cells, metal loading inactivated binding activity and activated enzyme activity. It also suppressed transferrin receptor mRNA expression in the cells. These results suggest that various non-Fe metals modulate IRP-1 by conversion of the 3Fe-4S apo-form to a [1 non-Fe metal + 3Fe] 4Fe holo-form. PMID- 11779156 TI - Endogenous anti-inflammatory mediators from arachidonate in human neutrophils. AB - Eicosanoids have been historically involved in the pathogenesis of various inflammatory diseases. Lipoxins (LXs) and epi-LXs show physiological effects relevant to inflammation regulation. In this study, we focused on LX precursors based on the hypothesis that their entrance and metabolism into the cell may facilitate their targeting at the inflammation site. Because compound chirality is of considerable importance in the efficacy of therapeutic agents, our aim was to study the anti-inflammatory effects of various epimers of LXA(4) precursors compared to LXA(4). Blood polymorphonuclear cells (PMNs) were incubated with 15(S)- or 15(R)-hydroxyeicosatetraenoic acid (HETE), 14(R)-,15(S)-, or 14(S),15(S)-diHETE, and LXA(4) and then stimulated with the calcium ionophore A23187. We found that 15(R)-HETE rather than 15(S)-HETE was preferentially metabolized and that 15-epi-LXs were produced in larger amounts than LXs. In contrast, when PMNs were incubated with the diastereoisomers of 14,15(S)-diHETE, 14-epi-LXB(4) was produced in lower amounts than LXB(4). Enantiomers of 15-HETE and diastereoisomers of 14,15-diHETE and LXA(4) were able to significantly decrease LTB(4) release by PMNs. These results suggest a potential resolution of the inflammatory process through endogenous anti-inflammatory mediators released by the way of trans-cellular metabolism. PMID- 11779157 TI - Physical interactions of Dmnk with Orb: implications in the regulated localization of Orb by Dmnk during oogenesis and embryogenesis. AB - The Dmnk (Drosophila maternal nuclear kinase) gene, encoding a nuclear protein serine/threonine kinase, is expressed predominantly in the germline cells during embryogenesis, suggesting its possible role in the establishment of germ cells. We report here that Dmnk interacts physically with Drosophila RNA binding protein Orb, which plays crucial roles in the establishment of Drosophila oocyte by regulating the distribution and translation of several maternal mRNAs. Considering similar spatiotemporal expression pattern of Dmnk and orb during oogenesis and early embryogenesis, it is suggested that Dmnk plays a role in establishment of germ cells by interacting with Orb. Although there are two forms of Dmnk proteins, Dmnk-L (long) and Dmnk-S (short) via the developmentally regulated alternative splicing, Orb can associate with both forms of Dmnk proteins when expressed in culture cells. However, immunohistochemical analysis revealed that Dmnk-S, but not Dmnk-L, can affect the subcellular localization of Orb in a kinase activity-dependent manner, suggesting differential functions of Dmnk-S and Dmnk-L in the regulation of Orb. PMID- 11779158 TI - Characterization of the mouse peroxisome proliferator-activated receptor delta gene. AB - Peroxisome proliferator-activated receptors (alpha, delta and gamma) are ligand activated transcription factors that are involved in multiple cellular responses. The PPARdelta subtype is the least understood of all PPAR subtypes. PPARdelta is activated by unsaturated fatty acids, PGI2, and by synthetic ligands. PPARdelta regulated genes have not been identified and the factors that control PPARdelta expression are not known. The gene that encodes the mouse PPARdelta gene is contained in >30 kb DNA sequence and organized in eight exons, six of which encode the PPARdelta receptor. A PPARdelta-luciferase reporter containing 694 bp 5' upstream regulatory and 127 bp untranslated was introduced to primary brain cultures to begin a characterization of the DNA sequences that mediate transcriptional regulation of PPARdelta. PPARdelta-luciferase expression was 10 times higher in oligodendrocyte-containing mature cultures than in immature cultures, indicating that PPARdelta may play a role during oligodendrocyte migration, proliferation, and/or maturation. PMID- 11779159 TI - Human lactoferrin activates transcription of IL-1beta gene in mammalian cells. AB - Lactoferrin (Lf) has been suggested to play roles in primary defense against microbial infection and other cellular processes including immunomodulation. Lf is known to bind to DNA and implicated to activate transcription. In the present study, we demonstrated that Lf stimulated transcription of IL-1beta gene, one of natural genes containing putative Lf binding site (LBS) in the 5'-flanking sequences. K562 cells treated with a combination of Lf and PMA showed a synergistic induction in the level of IL-1beta mRNA over treatment with PMA alone. Synergistic stimulation of IL-1beta expression by Lf and PMA was also confirmed by IL-1beta/Luc reporter gene assays. Analysis of Lf domains revealed that the transcriptional domain of Lf is located within the N-terminal 90 amino acids, termed NIa and that the C-terminal half lobe lacked the transactivating activity. The NIa, the N-terminal half lobe as well as intact Lf stimulated transcription of IL-1beta gene in the transfected K562 cells along with PMA, while the C-terminal half lobe did not. Our results suggest that Lf may play some roles in transcription of IL-1beta gene and may also regulate transcription of other natural genes containing LBS. PMID- 11779160 TI - TT virus is distributed in various leukocyte subpopulations at distinct levels, with the highest viral load in granulocytes. AB - When TT virus (TTV) DNA was quantitated in whole blood and plasma aliquots from 27 viremic individuals by real-time detection PCR that can detect essentially all TTV genotypes, the TTV load was 6.9 +/- 3.5 (mean +/- standard deviation)-fold higher in the whole blood than in the plasma samples [P < 0.002 (paired t test)]. To clarify the reason for this difference, peripheral blood cells of various types including red blood cells, granulocytes (CD15+), B cells (CD19+), T cells (CD3+), monocytes (CD14+), and NK cells (CD3-/CD56+) were separated at a purity of 95.4-99.5% from each of three infected individuals with relatively high TTV viremia, and their TTV viral loads were determined. Red blood cells were uniformly negative, but the other cell types were positive for TTV DNA at various titers. In all three patients, the highest TTV load was found in granulocytes (4.2 x 10(4)-3.1 x 10(5) copies/10(6) cells), followed by monocytes (1.4-2.2 x 10(4) copies/10(6) cells) and NK cells (5.4-6.5 x 10(3) copies/10(6) cells); B and T cells were positive, with a low viral load (6.7 x 10(1)-2.7 x 10(3) copies/10(6) cells). These results indicate that TTV is distributed in various peripheral blood cell types at distinct levels, with the highest viral load in granulocytes, and that a significant proportion of the TTV DNA in peripheral blood is not identified by the standard plasma/serum DNA detection methods. PMID- 11779161 TI - Prostaglandin E(2) stimulates prostatic intraepithelial neoplasia cell growth through activation of the interleukin-6/GP130/STAT-3 signaling pathway. AB - Cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) secretion are increased in prostatic intraepithelial neoplasia (PIN) and prostate cancer. PGE(2) biosynthesis by cyclooxygenase (COX)-2 plays a pivotal role in inflammation and carcinogenesis. One of the critical proinflammatory cytokines in the prostate is interleukin-6 (IL-6). We hypothesized that increased expression of COX-2, with resultant increased levels of PGE(2) in human PIN cells, activates the IL-6 signaling pathway. We demonstrate an autocrine upregulation of PGE(2) mediated by IL-6 in a human PIN cell line. We further demonstrate that PGE(2) stimulates soluble IL-6 receptor (sIL-6R) release, gp130 dimerization, Stat-3 protein phosphorylation, and DNA binding activity. These events, induced by PGE(2), lead to increased PIN cell growth. Treatment of PIN cells with a selective COX-2 inhibitor decreases cell growth. Finally, PGE(2)-stimulated PIN cell growth was abrogated by the addition of IL-6 neutralizing antibodies. These data provide mechanistic evidence that increased expression of COX-2/PGE(2) contributes to prostate cancer development and progression via activation of the IL-6 signaling pathway. PMID- 11779162 TI - Regulation of the rat SREBP-1c promoter in primary rat hepatocytes. AB - We have cloned 5 kb of genomic DNA encompassing 1.72 kb of 5'-regulatory sequence and exons 1-c and 2 of the rat SREBP-1c gene. A 1.5-kb segment upstream from the transcription start site was ligated ahead of the luciferase reporter gene and tested for promoter activity by transient transfection assays in primary rat hepatocytes. We discovered that insulin strongly activated the full-length promoter, regardless of whether 5 or 20 mM glucose was in the culture medium during treatment. Stimulation by insulin was blocked by dibutyryl-cAMP and by polyunsaturated fatty acids, such as alpha-linolenic acid, gamma-linolenic acid, or eicosapentaenoic acid; palmitic or oleic acids, however, had no inhibitory effect. A truncated promoter containing 149 bp of 5' flanking DNA, including proximal NF-Y, E-box, SRE, and Sp1 sites, retained most of the response. This is the first report that insulin, cAMP, and polyunsaturated fatty acids modulate the proximal SREBP-1c promoter in rat hepatocytes mirroring physiological regulation of SREBP-1c in vivo. PMID- 11779163 TI - 5-amino-4-imidazolecarboxamide riboside confers strong tolerance to glucose starvation in a 5'-AMP-activated protein kinase-dependent fashion. AB - Acadesine, 5-amino-4-imidazolecarboxamide riboside (AICAR), has been claimed to protect the heart, lung, and small intestine against ischemic damage. The biochemical mechanisms of this effect of AICAR are not yet fully understood. To understand the mechanism, we examined the effect of AICAR on glucose starvation, since cellular responses to ischemia could be regarded as a protective response to an insufficient blood supply, cells might display adaptive reactions not only to oxygen deficiency but to nutrient deficiency. AICAR was found to confer strong tolerance to glucose starvation. By using antisense RNA expression vector for alpha subunit of 5'-AMP-activated protein kinase, the effect of AICAR was found to be dependent on 5'-AMP-activated protein kinase containing the alpha2 subunit. The AICAR effect was also dependent on the presence of amino acids, indicating an energy source switch from glucose to amino acids. PMID- 11779164 TI - Actin cytoskeleton is required for early apoptosis signaling induced by anti-Fas antibody but not Fas ligand in murine B lymphoma A20 cells. AB - Murine B lymphoma A20 cells are highly sensitive to Fas-mediated death signals induced by anti-Fas antibody Jo2 or cross-linked Fas ligand (FasL). We have found that the microfilament poison cytochalasin D blocks Fas-mediated apoptosis induced by Jo2 but not FasL in A20 cells. The induction of Fas-mediated apoptosis by Jo2 was antagonized by anti-Fcgamma RII/RIII receptor (FcgammaR) antibody, and defective in FcgammaR-negative A20 cells. Since the induction of Jo2-mediated apoptosis in FcgammaR-negative A20 cells was reversed by the addition of wild type A20 cells or the cross-linking agent protein A, Fas-expressing bystander A20 cells seem to be killed by other A20 cells that capture and cross-link monomeric Jo2 via FcgammaR. Although cytochalasin D affected FcgammaR-mediated cross linking of Jo2 molecules, the drug markedly inhibited the intracellular signaling pathway induced by Jo2. The blockade of Jo2-induced apoptosis by cytochalasin D occurred upstream of caspase-8 activation. Thus, these observations suggest that actin cytoskeleton is required for early apoptosis signaling induced by Jo2, but not physiological FasL. PMID- 11779166 TI - A novel isoform of vertebrate ancient opsin in a smelt fish, Plecoglossus altivelis. AB - Vertebrate ancient (VA) opsin of nonvisual pigment in fishes was reported to exist in two isoforms, i.e., short and long variants with an unusual predicted amino acid sequence length compared to vertebrate visual opsins. Here we cloned an isoform (Pal-VAM) of VA opsin showing the usual opsin length in addition to the long type isoform (Pal-VAL) from a smelt fish, Plecoglossus altivelis. Pal VAM and Pal-VAL were composed of 346 and 387 amino acids, respectively. The deduced amino acid sequences of these variants were identical to each other within the first 342 residues, but they showed divergence in the carboxyl terminal sequence. Pal-VAL corresponded to the long isoform found in zebrafish and carp, and Pal-VAM was identified as a new type of VA opsin variant. Southern blotting experiments indicated that the VA opsin gene of the smelt is present as a single copy, and RT-PCR analysis revealed that Pal-VAM and Pal-VAL mRNA were expressed in both the eyes and brain. In situ hybridization showed that Pal-VAM and Pal-VAL mRNA are expressed in amacrine cells in the retina. Pal-VAM is a new probably functional nonvisual photoreceptive molecule in fish. PMID- 11779165 TI - Comparative carcinogenicity of picene and dibenz[a,h]anthracene in the rat. AB - Early carcinogenicity tests found no evidence of activity for picene but found considerable initiating and carcinogenic activity for dibenz[a,h]anthracene (DBA). More recent investigation suggested that both pentacyclics were complete carcinogens when administered as single sc injections in NMRI mice, despite findings that picene acted as neither an initiating nor promoting agent. To investigate this contradiction, the complete carcinogenicities of both isomers were compared by sc injection in female Sprague-Dawley rats. The results demonstrate that 1 micromol of DBA, administered three times weekly for 20 doses, induces sarcomas in all test animals by 33 weeks (100%). Similar treatment with picene did not induce sarcoma in any test animals by 37 weeks (0%). The present results agree with the earlier studies. It follows from these results that the predictions of the unified theory for the appearance of carcinogenic properties following administration of picene and dibenz[a,h]anthracene to test animals have been confirmed. PMID- 11779167 TI - Functional expression and characterization of Aedes aegypti dopachrome conversion enzyme. AB - A full-length mosquito dopachrome conversion enzyme (DCE) and its truncated form lacking the last 54 carboxyl-terminal amino acid residues are expressed using a baculovirus/insect cell expression system. The full-length recombinant DCE displayed multiple bands during native PAGE with substrate staining, but only one active band was detected when the truncated recombinant DCE was analyzed under identical analysis conditions. Our data suggest that the last 50 some carboxyl terminal residues are involved in the polymerization of the DCE molecules and that the proposed DCE isozymes likely reflect the presence of multimers of the same DCE molecules. The significance of the recombinant DCE in accelerating the melanization pathway is demonstrated by a rapid production of melanin in a dopa and tyrosinase reaction mixture in the presence of recombinant DCE. The DCE sequence data obtained in our previous study, together with results of functional expression and biochemical characterization achieved in this study, provide a necessary reference for the study of other insect DCEs. PMID- 11779169 TI - In vitro self-assembled HCV core virus-like particles induce a strong antibody immune response in sheep. AB - The in vitro self-assembly properties of the entire hepatitis C virus core protein (HCcAg) obtained from Pichia pastoris cells and the induction of specific antibody immune response were studied. HCcAg was purified as a low-molecular weight species by electroelution under denaturing conditions for confirmation of its self-assembly properties. After renaturalization, electron microscopy showed that HCcAg assembled into spherical particles of 30 nm. HCcAg also showed homogeneity and was specifically recognized by serum from a chronic HCV carrier patient. The data indicated that in vitro assembly of HCcAg, into virus-like particles resembling HCV nucleocapsid particles at a mature stage, is an intrinsic quality of this protein. Finally, HCcAg generated a strong antibody immune response in sheep, suggesting its usefulness for stimulating the host immune response against HCV. PMID- 11779168 TI - Cobalt- and nickel-binding property of cullin-2. AB - Treatment with divalent metal ions such as cobalt (Co(2+)) or nickel (Ni(2+)) result in the stabilization of hypoxia-inducible factor-1alpha (HIF1alpha). Recently, HIF1alpha was shown to be ubiquitinated by an E3-ligase complex and be subsequently targeted for proteasomal degradation. In this study, we demonstrated that Co(2+) and Ni(2+) specifically bind to cullin-2. Mutant analysis revealed that cullin-2 possesses at least three sites for the binding. Furthermore, fluorescence spectroscopy revealed that only Co(2+) and Ni(2+) have the binding activity to cullin-2, but other metal ions, including Cu(2+), Ca(2+), Mg(2+), Mn(2+), and Zn(2+), did not. Finally, we found that Co(2+) and Ni(2+) do not bind to any components of the E3-ligase other than cullin-2, suggesting that cullin-2 is a key target of Co(2+) and Ni(2+). Interestingly, Co(2+) did not affect the complex formation of the ligase, suggesting that the metal binding to cullin-2 affects the function, but not the assembly of the E3-ligase. PMID- 11779170 TI - Production of soluble integrin alpha2beta1 heterodimer complex functionally active in vitro and in vivo. AB - Integrin alpha2beta1, which is a membrane protein consisting of noncovalently bound alpha2 and beta1 chains, mediates cell binding to collagen and plays a role in platelet functions. DNAs encoding the chimeric proteins in which the extracellular domains of each alpha2 and beta1 chain was fused to hinge and Fc regions of human IgG(1)gamma chain were cotransfected into CHO cells. Soluble integrin alpha2beta1 (salpha2beta1) in which alpha2 and beta1 chains were covalently bound by disulfide bonds was recovered from the culture supernatant. salpha2beta1 maintained functional characteristics of cell surface alpha2beta1 as indicated by cation-dependent binding to collagen and conformational changes induced by cations or ligand. Intravenously administered salpha2beta1 in rats colocalized with collagen in inflamed microvessels. Moreover, salpha2beta1 conjugated liposome administered intravenously reduced bleeding time of the thrombocytopenic mice. These results indicated that salpha2beta1 has pharmaceutical utilities as an agent for detecting injured vessels and a component of platelet substitute. PMID- 11779171 TI - Class VI myosin moves processively along actin filaments backward with large steps. AB - Among a superfamily of myosin, class VI myosin moves actin filaments backwards. Here we show that myosin VI moves processively on actin filaments backwards with large ( approximately 36 nm) steps, nevertheless it has an extremely short neck domain. Myosin V also moves processively with large ( approximately 36 nm) steps and it is believed that myosin V strides along the actin helical repeat with its elongated neck domain that is critical for its processive movement with large steps. Myosin VI having a short neck cannot take this scenario. We found by electron microscopy that myosin VI cooperatively binds to an actin filament at approximately 36 nm intervals in the presence of ATP, raising a hypothesis that the binding of myosin VI evokes "hot spots" on actin filaments that attract myosin heads. Myosin VI may step on these "hot spots" on actin filaments in every helical pitch, thus producing processive movement with 36 nm steps. PMID- 11779172 TI - An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles. AB - We developed genotyping assays for CYP2A6*7 (Ile471Thr) and CYP2A6*8 (Arg485Leu). We found higher allelic frequencies in Japanese and Chinese versus Caucasians and identified an allele in which both substitutions occur together (CYP2A6*10). We created a homology model for predicting the impact of allelic variants on enzymatic activity and subsequently tested this in vivo in a pilot kinetic study. Consistent with our homology model predictions, we found (i) that CYP2A6*7 produces an enzyme that has decreased (not inactive) activity for metabolizing nicotine and coumarin; (ii) that CYP2A6*8 is unlikely to affect catalytic activity in vivo; and (iii) that having both substitutions together on an allele (CYP2A6*10) dramatically reduces function and may be fully inactive for some substrates. In conclusion, this study identifies, at relatively high frequency in Asians, an allele with decreased activity (may be substrate selective), a fully functional allele, and an allele containing both substitutions in which function is dramatically reduced. PMID- 11779173 TI - Oxygen tension regulates the maturation of the blood-brain barrier. AB - The oxygen tension during the development of vascular systems influences vascular vessel formation through regulating angiogenesis. We studied the effect of hypoxia/reoxygenation (H/R) to explain its role in concert with astrocytes involvement in the development of the blood-brain barrier (BBB). On the basis of the fact that the disappearance of hypoxic regions and the decreased expression of vascular endothelial growth factor (VEGF) were observed by immunohistochemistry in a development-dependent manner in rat cerebral cortex, we examined the effects of astrocytes on the BBB-like properties of ECV304 cells by exposing astrocytes to H/R. Conditioned medium of reoxygenated astrocytes inhibited [(3)H]thymidine incorporation and tube formation of ECV 304 cells. When astrocytes were exposed to reoxygenation, the expression of VEGF was reduced, whereas the expression of angiopoietin-1 and thrombospondin-1 was enhanced. Moreover, [(3)H]sucrose permeability assay revealed that astrocytes enhance the barrier function of ECV 304 cells in coculture model within 5 h of reoxygenation. Correspondingly, the occludin expression of ECV 304 cells was slightly increased by the conditioned medium of reoxygenated astrocytes. In conclusion, our study suggests that reoxygenation of astrocytes may act as a significant driving force for the maturation of the BBB during brain development through oxygen-regulated gene(s). PMID- 11779174 TI - Utilizing chimeric proteins for exploring the cellular fate of endogenous proteins. AB - We recently designed and constructed chimeric proteins for the elimination of specific cell populations. These chimeric proteins are composed of a targeting component fused to an apoptotic protein as the killing moiety. However, chimeric proteins can serve not only to eliminate cell populations, but also as "biological tools" for studying the fate of endogenous proteins. We show here that upon entering their target cell, a variety of chimeric proteins composed of an endogenous protein as their killing moiety reach the subcellular location of their endogenous counterpart. In contrast, bacterial-based killing domains head for the subcellular site of their substrate. Moreover, the chimeric protein acts similarly to the endogenous protein, while causing the cell to die. Therefore, chimeric proteins may serve as a unique tool for investigating cellular proteins and their intracellular localization, without the need to overexpress them. PMID- 11779175 TI - Salt stress and hyperosmotic stress regulate the expression of different sets of genes in Synechocystis sp. PCC 6803. AB - Acclimation of microorganisms to environmental stress is closely related to the expression of various genes. We report here that salt stress and hyperosmotic stress have different effects on the cytoplasmic volume and gene expression in Synechocystis sp. PCC 6803. DNA microarray analysis indicated that salt stress strongly induced the genes for some ribosomal proteins. Hyperosmotic stress strongly induced the genes for 3-ketoacyl-acyl carrier protein reductase and rare lipoprotein A. Genes whose expression was induced both by salt stress and by hyperosmotic stress included those for heat-shock proteins and the enzymes for the synthesis of glucosylglycerol. We also found that each kind of stress induced a number of genes for proteins of unknown function. Our findings suggest that Synechocystis recognizes salt stress and hyperosmotic stress as different stimuli, although mechanisms common to the responses to each form of stress might also contribute to gene expression. PMID- 11779176 TI - TGF-alpha-driven tumor growth is inhibited by an EGF receptor tyrosine kinase inhibitor. AB - The simultaneous presence of the EGFR and its ligand TGF-alpha in human tumor tissues suggests that autocrine TGF-alpha stimulation drives tumor growth. Here we show that autocrine TGF-alpha stimulation does cause increased tumor growth in vivo, an effect that was proven to be mediated via EGFR activation, and that this TGF-alpha/EGFR autocrine loop was accessible to an EGFR specific tyrosine kinase inhibitor. Clones of the EGFR expressing glioma cell line U-1242 MG were transfected with TGF-alpha cDNA using a tetracycline-inhibitory system for gene expression. TGF-alpha expression was inhibited by the presence of tetracycline, and subcutaneous tumors forming from cell lines injected into nude mice could be inhibited by feeding mice tetracycline. We confirmed that TGF-alpha mRNA and protein were present in these tumors and that, subsequently, the endogenous EGFR was activated. Tumor growth could be inhibited by an EGFR specific tyrosine kinase inhibitor of the type 4-(3-chloroanilino)-6,7-dimethoxy-quinazoline, administered daily by intraperitoneal injection, thereby interrupting the autocrine loop. PMID- 11779177 TI - Subcellular localization, oligomerization, and ATP-binding of Caenorhabditis elegans CED-4. AB - Caspase family cell death proteases are activated during apoptosis through the oligomerization of caspase-binding "adapter" proteins. In the nematode Caenorhabditis elegans one adapter protein, CED-4, exists. Here we report an analysis of CED-4 protein expressed in insect Sf9 cells by infection with recombinant baculovirus. During expression, CED-4 assumed a perinuclear spherical or reticular localization where it was partly resistant to extraction with nonionic detergents. Both purified FLAG-CED-4 and GST-FLAG-CED-4 proteins were present in solution as large complexes. FLAG-CED-4 complexes were estimated by gel filtration to have a molecular weight of approximately 500 kDa to >1.2 MDa, while GST-FLAG-CED-4 complexes appeared somewhat smaller. Unlike its mammalian homologue Apaf-1, CED-4 exhibited a marked preference for ATP over dATP in filter binding studies and in competition experiments. ATP hydrolysis was required neither for complex stability nor for binding of CED-3. These features are likely to be relevant for CED-4's function as a caspase adapter. PMID- 11779178 TI - Effects of Nf2 missense mutations on schwannomin interactions. AB - Most benign brain tumors are associated with loss of the Nf2 gene tumor suppressor product schwannomin/merlin. Interactions between schwannomin fragments have given rise to hypotheses of in vivo schwannomin folding and dimerization. Previously, we showed that schwannomin with missense mutations L360P, L535P, and Q538P alters interaction with betaII-spectrin and Hrs. Using yeast two-hybrid tests of interaction, we now show the effects of 11 Nf2 missense mutations on schwannomin self-interaction as well as schwannomin interaction with Hrs isoforms 1 and 2, betaII-spectrin, and p110. Missense mutations L46R and K364I significantly decreased affinity of schwannomin for binding all interacting proteins. The schwannomin L46R mutation may result in a complex conformational change that alters folding and denies betaII-spectrin access to an intact binding site in the C-terminal half of schwannomin. We show that unique inter- and intramolecular interactions occur for schwannomin isoform 2, suggesting that this schwannomin isoform has unique functional properties compared to schwannomin isoform 1. PMID- 11779179 TI - Dimerization of phospholipase d isozymes. AB - Two mammalian phospholipase D (PLD) isozymes (PLD1 and PLD2) have been reported. In this study, we differentially tagged these isozymes with enhanced green fluorescent protein (EGFP-rPLD1 and EGFP-rPLD2) or Xpress peptide epitope (Xpress rPLD1 and Xpress-rPLD2) to examine the association between these isozymes. Overexpressed EGFP-rPLD1 coimmunoprecipitated with Xpress-rPLD1 using anti-Xpress antibody. However, the coimmunoprecipitation was independent of the activity of rPLD1. Xpress-rPLD2 also bound to EGFP-rPLD1 although the binding was less efficient than observed with Xpress-rPLD1. The association between rPLD2 and rPLD1 was confirmed by coimmunoprecipitation of EGFP-rPLD2 with Xpress-rPLD1. EGFP-rPLD2 also bound to Xpress-rPLD2 as shown by coimmunoprecipitation. Immunofluorescence staining of COS-7 cells coexpressing EGFP-rPLDs and Xpress rPLDs showed that the PLD isozymes colocalized in the perinuclear and plasma membrane regions, suggesting that they could associate in a cellular setting. These results suggest that rPLD1 and rPLD2 can exist as homodimers and can form heterodimers. PMID- 11779180 TI - Genome-wide screening by cDNA microarray of genes associated with matrix mineralization by human mesenchymal stem cells in vitro. AB - Using a culture system that facilitates osteogenic differentiation of bone marrow derived human mesenchymal stem cells, we analyzed gene-expression profiles during the mineralization process by means of a cDNA microarray system consisting of 23,040 genes. We compared expression profiles of the cells at days 3, 15, and 27 of incubation in media containing either a combination of 0.1 microM dexamethasone, 0.05 mM ascorbic acid-2-phosphate, and 10 mM beta glycerophosphate, dexamethasone only, ascorbic acid-2-phosphate plus beta glycerophosphate, or medium without any of these osteogenic supplements. Histochemical analysis revealed osteogenic differentiation of cells incubated in the presence of all three agents, but not in the other cultures. Comparison of the expression profiles disclosed transcriptional stimulation of 55 genes and repression of 82 genes among more than 20,000 examined. A set of differentially expressed genes we report here should contribute to a better understanding of the process of mineralization in the matrix surrounding human mesenchymal stem cells. PMID- 11779181 TI - Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. AB - Paraoxonase (PON-1) is a high-density lipoprotein (HDL)-bound enzyme with activity toward multiple substrates. It hydrolyzes organic phosphate and aromatic carboxylic acid esters. It also inhibits accumulation of oxidized phospholipids in plasma lipoproteins by a mechanism yet to be determined. Therefore, we subjected apolipoprotein A-I proteoliposomes containing either 1-palmitoyl-2 linoleoyl-sn-glycero-3-phosphocholine or 1-palmitoyl-2-arachidonoyl-sn-glycero-3 phosphocholine to oxidation by a peroxynitrite generator, SIN-1, in the presence and absence of purified PON-1. PON-1 modified the proportion of oxidation products without affecting the overall extent of PC oxidation. However, in the presence of PON-1, phosphatidylcholine isoprostanes were hydrolyzed to lysophosphatidylcholine. In addition, PON-1 hydrolyzed the phosphatidylcholine core aldehydes 1-palmitoyl-2-(9-oxo)nonanoyl-sn-glycero-3-phosphocholine and 1 palmitoyl-2-(5-oxo)valeroyl-sn-glycero-3-phosphocholine to lysophosphatidylcholine. This hydrolysis was not affected by pefabloc, a serine esterase inhibitor. There was no detectable release of linoleate, arachidonate, or their hydroperoxy or hydroxy derivatives in the presence of PON-1. We conclude that PON-1 minimizes the accumulation of phosphatidylcholine oxidation products by the hydrolysis of phosphatidylcholine isoprostanes and core aldehydes to lysophosphatidylcholine with a serine esterase-independent mechanism. PMID- 11779182 TI - Measuring beta-galactosidase activity in bacteria: cell growth, permeabilization, and enzyme assays in 96-well arrays. AB - We describe a high-throughput procedure for measuring beta-galactosidase activity in bacteria. This procedure is unique because all manipulations, including bacterial growth and cell permeabilization, are performed in a 96-well format. Cells are permeabilized by chloroform/SDS treatment directly in the 96-well blocks and then transferred to 96-well microplates for standard colorimetric assay of beta-galactosidase activity as described by Miller [J. H. Miller (1972) Experiments in Molecular Genetics, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY]. Absorbance data are collected with a microplate reader and analyzed using a Microsoft Excel spreadsheet. The beta-galactosidase specific activity values obtained with the high-throughput procedure are identical to those obtained by the traditional single-tube method of Miller. Thus, values obtained with this procedure may be expressed as Miller units and compared directly to Miller units reported in the literature. The 96-well format for permeabilization and assay of enzyme specific activity together with the use of 12-channel and repeater pipettors enables efficient processing of hundreds of samples in an 8-h day. PMID- 11779183 TI - Paternal expression of a novel imprinted gene, Peg12/Frat3, in the mouse 7C region homologous to the Prader-Willi syndrome region. AB - Paternally expressed imprinted genes (Pegs) were systematically screened by comparing gene expression profiles of parthenogenetic and normal fertilized embryos using an oligonucleotide array. A novel imprinted gene, Peg12/Frat3, was identified along with 10 previously known Pegs. Peg12/Frat3 is expressed primarily in embryonic stages and might be a positive regulator of the Wnt signaling pathway. It locates next to the Zfp127 imprinted gene in the mouse 7C region, which has syntenic homology to the human Prader-Willi syndrome region on chromosome 15q11-q13, indicating that this imprinted region extends to the telomeric side in the mouse. PMID- 11779184 TI - Role for O-glycosylation of RFP in the interaction with enhancer of polycomb. AB - We recently demonstrated that RFP, which belongs to the large B-box RING finger protein family, interacts with Enhancer of Polycomb 1 (EPC1) and functions as a transcriptional repressor in human cultured cells. In this study, we examined the expression of RFP and EPC1 in mouse tissues by immunoblotting as well as their interaction by a pull-down assay. Both RFP and EPC1 proteins are expressed in several mouse tissues including testis, spleen, thymus, adrenal gland, cerebrum, and cerebellum. In addition, they were coprecipitated from the lysate of mouse testis. Pull-down assays using glutathione S-transferase (GST)-fused EPC1 proteins revealed that RFP is associated with the EPcA, EPcB, and carboxy terminal (CT) regions of EPC1. Although RFP is highly expressed as 58- and 68-kDa proteins in mouse testis, the EPC1 CT region more strongly interacted with the 68 kDa form than the EPcA or EPcB region. Interaction of the 58-kDa form of RFP with each region was weak compared with that of the 68-kDa form with the EPC1 CT region. Because the 68-kDa form of RFP was almost completely digested with O glycosidase but not with N-glycosidase, this suggested that O-glycosylation of RFP plays a role in its interaction with the EPC1 CT region that may be responsible for transcriptional repression. In addition, the luciferase reporter gene assay showed that expression of the EPcA region strongly impairs the transcriptional repressive activity of RFP. PMID- 11779185 TI - REST4-mediated modulation of REST/NRSF-silencing function during BDNF gene promoter activation. AB - Neural-restrictive silencer element (NRSE)/repressor element-1 (RE1) regulates neuron-specific gene expression by binding the transcriptional factor REST/NRSF which functions as a silencer in nonneuronal cells. In neuronal cells, a truncated, neuronal-specific REST/NRSF isoform, REST4, has been found but little is known about its function. To address this, we investigated the effect of REST/NRSF and REST4 on the activity-dependent activation of BDNF gene promoter I (BDNFp-I) using cultured rat cortical neurons. REST/NRSF markedly repressed the transcriptional activation of BDNFp-I, whereas the effect of REST4 was weak, depending upon the NRSE/RE1 sequence. In addition, REST4 enhanced the basal transcriptional activity of BDNFp-I. Coexpression of REST4 with REST/NRSF competitively inhibited the silencing effect of REST/NRSF on the activation of BDNFp-I. Although REST4 itself has a weak repressive effect on activation of the BDNF gene via NRSE/RE1, it can compete the silencing effect of REST/NRSF, suggesting a primary role for REST4 in preventing the neuron-specific gene from being inactivated by REST/NRSF and allowing gene activation in response to a variety of neuronal stimuli. PMID- 11779186 TI - The flexible C-terminal region of Aspergillus terreus blasticidin S deaminase: identification of its functional roles with deletion enzymes. AB - Although the four polypeptides of blasticidin S (BS) deaminase (BSD) are packed rather tightly coordinated to the "structural and catalytic" zinc atom of each subunit, the C-terminal region of the enzyme was suggested to be somewhat molten and flexible [M. Kimura, S. Sekido, Y. Isogai, and I. Yamaguchi (2000) J. Biochem. 127, 955-963]. To understand roles of this flexible region, we constructed five C-terminal deletion variants of BSD (each successively deleted from the C-terminal end up to five residues) and analyzed their biochemical properties focusing on the structure and activity of the enzyme. BSD and all of the deletion mutants showed the unique rigid conformation (e.g., characterized by their stabilities in SDS solution) and high levels of resistance against protease digestions. Furthermore, both the wild-type and deletion apoenzymes exhibited similar physical properties in thermodynamic refolding into the stable tetramer conformation. However, these small C-terminal deletions exerted deleterious effects on the catalytic efficiency of the enzyme as indicated by their strongly reduced k(cat)/K(m) value. Judging from the altered kinetic parameters and unaltered structural properties of the deletion variants, these C-terminal residues appear to be directly involved in enzyme-substrate interaction. In this short flexible region, Tyr-126, Trp-128, and Gly-130 were the key residues. Most notably, removal of Gly-130 markedly increased K(m) for BS without affecting its k(cat) value. These results indicate that the flexible C-terminal region is important for catalytic function and that a single Gly residue at the C-terminal end of BSD contributes significantly in facilitating access of a substrate to the active site. PMID- 11779187 TI - A study on the C-terminal membrane anchoring of Escherichia coli penicillin binding protein 5. AB - Escherichia coli penicillin-binding protein 5 (PBP5) anchors to the inner membrane in a pH-dependent manner via a C-terminal amphiphilic alpha-helix. Low pH was found to enhance both levels of PBP5 membrane anchoring and levels of alpha-helicity in an aqueous PBP5 C-terminal homologue, which led to the suggestion that levels of PBP5 membrane anchoring are related to levels of PBP5 C terminal alpha-helicity. Here we have used Fourier-transformed infrared spectroscopy (FTIR) and a peptide homologue of the PBP5 C-terminal sequence to investigate the effect of pH on the conformational behavior of this sequence at a lipid interface and on its ability to interact with lipid. Our results suggest that the membrane-anchoring mechanism of PBP5 is unlikely to involve conformational change in the protein's C-terminal region and may therefore involve conformational changes in the protein's ectomembranous domain. PMID- 11779188 TI - Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein. AB - Nedd-4-like proteins are E3 ubiquitin-ligase molecules which regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Here we show that a human Nedd4 family gene, WWP1, is localized on 8q21 and generates at least six isoforms through alternative splicing. We show that alternative splicing affects the domain structure of WWP1, with forms that contain or lack an N-terminal C2 domain. Interestingly, the relative ratio of these forms varies in a tissue-specific manner. Other splice forms were also identified which may disrupt the structure of the C2 domain by removing its predicted C-terminal beta-strands. One splice form generates, through the introduction of a reading frame shift, a C2 domain-only form of WWP1. We discuss the hypothesis that regulation of splice site usage may modulate the activity of WWP1 and possibly other Nedd4 family proteins. PMID- 11779189 TI - Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy. AB - IgA nephropathy is characterized by the deposition of IgA immune complexes in the glomerular mesangium, but the mechanisms responsible for this are not well understood. Human mesangial cells (HMCs) can bind IgA but do not express known IgA receptors. We show here that primary HMCs express mRNA for a novel receptor, the Fc alpha/mu receptor (Fcalpha/muR), and that receptor expression is upregulated by IL-1. We also detected mRNA for a novel receptor variant in HMCs that may encode a soluble form of the receptor. Fcalpha/muR was expressed in a heterologous system which showed that the receptor was approximately 58 kDa in weight and was only minimally N-glycosylated. As predicted from the characteristics of the murine homologue, the expressed human Fcalpha/muR was able to bind IgA and IgM, but not IgG. These results suggest that Fcalpha/muR may be the receptor responsible for mesangial IgA deposition in IgA nephropathy. PMID- 11779190 TI - Cell surface trafficking of Fas in NIT-1 cells and dissection of surface and total Fas expression. AB - The appearance of Fas receptor at the surface of pancreatic beta-cells affected by progressive insulitis strongly suggests that Fas-mediated beta-cell apoptosis plays an important role in the pathogenesis of type 1 diabetes. In support of this concept, the present study has shown that islet cells from NOD mice and the beta-cell line NIT-1 respond to the proinflammatory cytokines IL-1beta and IFN gamma with Fas surface expression in a dose- and time-dependent manner. Moreover, the prevention of cytokine-induced surface Fas expression by actinomycin D, cycloheximide, and brefeldin A demonstrated that trafficking of Fas to the beta cell surface requires RNA and protein synthesis and, in addition is critically dependent on intracellular protein transport. Compared with total cellular Fas protein, the amount of Fas at the cell surface was relatively small and indicated that Fas is preferentially expressed in cytoplasmic compartments of NIT-1 cells. It is concluded that inflammatory insults specifically induce translocation of Fas to the beta-cell surface and that interference with cell surface Fas expression is a new strategy to improve beta-cell survival in inflamed islets. PMID- 11779191 TI - Identification of a novel protease inhibitor gene that is highly expressed in the prostate. AB - A novel gene was identified 52 kb upstream of the gene encoding the protease inhibitor elafin (PI3) on human chromosome 20q12-13.1. The transcript of the new gene, denoted huWAP2, was characterized by rapid amplification of cDNA ends and DNA sequencing. The size is 774 bp and it gives rise to a polypeptide of 111 amino acid residues that is homologous to elafin and similar WAP-type protease inhibitors. By RT-PCR it was shown that the gene is highly expressed in prostate, skin, lung, and esophagus. PMID- 11779192 TI - Soybean ascorbate peroxidase suppresses Bax-induced apoptosis in yeast by inhibiting oxygen radical generation. AB - Bax, a mammalian proapoptotic member of the Bcl-2 family, can induce cell death when expressed in yeast or plant cells. To identify plant Bax inhibitors, we cotransformed a soybean cDNA library and the Bax gene into yeast cells and screened for expressed genes that prevented Bax-induced apoptosis. From the Bax inhibiting genes isolated, ascorbate peroxidase (sAPX) was selected for characterization. The transcription of sAPX in plants was specifically induced by oxidative stress. Moreover, overexpression of sAPX partially suppressed the H(2)O(2)-sensitive phenotype of yeast cytosolic catalase T (Deltactt)- and thermosensitive phenotype of cytochrome c peroxidase (Deltaccp)-deleted mutant cells. Examination of reactive oxygen species (ROS) production using the fluorescence method of dihydrorhodamine 123 oxidation revealed that expression of Bax in yeast cells generated ROS, which was greatly reduced by coexpression with sAPX. Our results collectively suggest that sAPX inhibits the generation of ROS by Bax, which in turn suppresses Bax-induced cell death in yeast. PMID- 11779193 TI - Phosphorylation of recombinant human spermidine/spermine N(1)-acetyltransferase by CK1 and modulation of its binding to mitochondria: a comparison with CK2. AB - Cytosolic spermidine/spermine acetyltransferase (SSAT) catalyzes the acetylation of the N(1)-propylamino groups of spermine and spermidine. The enzyme has a very short half-life and is rapidly induced by various stimuli. Once acetylated, these polyamines are subjected to the action of polyamine oxidase, which, besides initiating polyamine catabolism, may produce reactive oxygen species that in turn trigger modifications in subcellular compartments such as mitochondria. The present work evaluates the ability of the cAMP-independent Ser/Thr-protein kinase CK1 to phosphorylate SSAT. Results demonstrate that SSAT is phosphorylated by CK1, in sites distinct from those phosphorylated by CK2. Moreover, both phosphorylation processes are involved in the uptake of SSAT into rat liver mitochondria. Although CK2 is less effective than CK1 in phosphorylating SSAT, CK2 phosphorylation is much more powerful in preventing binding of SSAT to mitochondrial structures. These results suggest the involvement of CK1- and CK2 mediated SSAT phosphorylation in regulating the contents of polyamines and SSAT itself within subcellular compartments and implicate SSAT and polyamines as indirect modulators of progression through the cell cycle. PMID- 11779194 TI - Proteasome inhibitors activate the transcription factors C/EBP-beta and delta in human intestinal epithelial cells. AB - In recent studies, induction of the heat shock response by hyperthermia upregulated the expression and DNA binding activity of the transcription factor C/EBP. This is an important observation because it may at least in part explain why the heat shock response upregulates IL-6 production in the intestinal mucosa and in the enterocyte. A novel method to induce the heat shock response is proteasome inhibition. The influence of this treatment on the expression and DNA binding activity of C/EBP is not known. We treated cultured Caco-2 cells, a human intestinal epithelial cell line, with one of the proteasome inhibitors, MG-132 or lactacystin, and measured C/EBP-beta and delta DNA binding activity by electrophoretic mobility shift assay and supershift analysis. In addition, nuclear levels of C/EBP-beta and delta protein were determined by Western blot analysis. Treatment of the cells with the proteasome inhibitors resulted in increased cellular levels of heat shock protein 72, consistent with induction of the heat shock response. Treatment also resulted in increased DNA binding activity and nuclear protein levels of C/EBP-beta and delta. The effects of the proteasome inhibitors on C/EBP were inhibited by treating the cells with quercetin, a substance known to block the heat shock response. The results suggest that proteasome inhibition activates the transcription factors C/EBP-beta and delta in human intestinal epithelial cells and that this response, at least in part, is caused by induction of the heat shock response. The observations are important because they provide support for a novel method to influence gene activation in the enterocyte. PMID- 11779195 TI - Exogenously administered HGF activator augments liver regeneration through the production of biologically active HGF. AB - Hepatocyte growth factor (HGF) plays a crucial role in the recovery of injured liver. Liver functions are mostly impaired in patients with liver diseases including cirrhosis. However, a significant amount of inactive HGF precursor (proHGF) is reported in the plasma of these patients. proHGF is proteolytically converted to an active form (mature HGF) by HGF-activator. Thus conversion of proHGF into mature HGF presumably contributes to the recovery of liver functions. In this study, rats with a partial hepatectomy were used, as proHGF is accumulated in the remnant liver. Recombinant human HGF-activator was administered via the portal vein to investigate the effect on molecular forms of HGF and its biological signaling. rhHGF-activator promptly converted proHGF into mature HGF, reaching maximal levels at 5-10 min after the injection, while the decreased proHGF was quickly recovered to the initial levels in the liver. The HGF receptor/c-Met was found to be autophosphorylated in the liver treated with rhHGF-activator. Further, the proliferating cell nuclear antigen labeling index and the liver regeneration rate were significantly higher in rhHGF-activator group than in control animals. These results indicate that exogenously administered HGF-activator produces a biologically active HGF from its precursor form and increases the potential for liver regeneration in vivo. PMID- 11779196 TI - Differential gene expression of organic anion transporters in male and female rats. AB - Sex-related differential gene expression of organic anion transporters (rOAT1, rOAT2, and rOAT3) in rat brain, liver, and kidney was investigated. There were no sex differences in the expression of rOAT1 mRNA. rOAT2 mRNA was abundant in the liver and weakly expressed in the kidney of male rats; however, the OAT2 gene was strongly expressed in both organs of females. The abundance of rOAT2 mRNA markedly increased in castrated male rat kidney; however, treatment of castrated male rats with testosterone led to a decrease of rOAT2 mRNA. Expression of rOAT3 mRNA in intact female rats was found in the kidney and brain, whereas in males rOAT3 mRNA was also found in the liver. rOAT3 mRNA markedly decreased in the liver of castrated male rats but increased in testosterone-treated castrated male rats. Moreover, rOAT3 mRNA increased in the hypophysectomized female rat liver, indicating that rOAT3 is an inducible isoform. The present findings suggest that sex steroids play an important role in the expression and maintenance of OAT2/3 isoforms in the rat liver and kidney. Our results provide information on the differential gene expression of OAT isoforms with sex hormone dependency. PMID- 11779197 TI - Effect of protein kinase C on endoplasmic reticulum cholesterol. AB - Plasma membrane cholesterol both regulates and is regulated by effector proteins in the endoplasmic reticulum (ER) through a feedback system that is poorly understood. We now show that ER cholesterol varies over a fivefold range in response to experimental agents that act upon protein kinase C (PKC). Agents that activate Ca(2+)-dependent PKC [phorbol-12-myristate-13-acetate (PMA) and bryostatin 1] increased the level of ER cholesterol; inhibitors such as staurosporine and calphostin C decreased it. Rottlerin, a selective inhibitor of the PKC-delta isoform, also increased ER cholesterol. The esterification of plasma membrane cholesterol was altered by protein kinase C-directed agents in a corresponding fashion. Furthermore, the regulatory effect of plasma membrane cholesterol on the esterification of ER cholesterol was blocked by PKC-directed agents. These findings suggest that multiple protein kinase C isoforms participate in the regulation of ER cholesterol and therefore in cholesterol homeostasis. PMID- 11779198 TI - Subsites of trypsin active site favor catalysis or substrate binding. AB - Enzymes enhance chemical reaction rates by lowering the activation energy, the energy barrier of the reaction leading to products. This occurs because enzymes bind the high-energy intermediate of the reaction (the transition state) more strongly than the substrate. We studied details of this process by determining the substrate binding energy (DeltaG(s), calculated from K(m) values) and the activation energy (DeltaG(T), determined from k(cat)/K(m) values) for the trypsin catalyzed hydrolysis of oligopeptides. Plots of DeltaG(T) versus DeltaG(s) for oligopeptides with 15 amino acid replacements at each of the positions P(1)', P(1), and P(2) were straight lines, as predicted by a derived equation that relates DeltaG(T) and DeltaG(s). The data led to the conclusion that the trypsin active site has subsites that bind moieties of substrate and of transition state in characteristic ratios, whichever substrate is used. This was unexpected and means that each subsite characteristically favors substrate binding or catalysis. PMID- 11779199 TI - DNA microarray analyses of genes elicited by ultrasound in human U937 cells. AB - The gene expression of human histiocytic lymphoma cell line U937 at 6 h after 1 MHz ultrasound treatment in the presence of Ar or N(2)O gas was examined by DNA microarrays. Of the 9,182 genes analyzed, only the keratin gene was identified as down-regulated in the cells exposed to ultrasound in the presence of N(2)O where no internal cavitation was observed. In contrast, five up-regulated and two down regulated genes were identified in the cells exposed to ultrasound in the presence of Ar where internal cavitation was apparently observed. Six changes of the gene expression were confirmed by the semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Gene expression of heme oxygenase was augmented by a factor of 6.6 in microarray and by 4.0 by RT-PCR. These results indicate that internal cavitation increased the expression of genes responsive to oxidative stress in sonicated cells but non-inertial cavitation had minimal effects on gene expression. PMID- 11779200 TI - ZK 156718, a low calcemic, antiproliferative, and prodifferentiating vitamin D analog. AB - The physiologically active form of vitamin D, 1,25-dihydroxyvitamin D(3), plays an important role not only in the establishment and maintenance of calcium metabolism, but also in regulating cell growth and differentiation. Because the clinical usefulness of 1,25-dihydroxyvitamin D(3) is limited by its tendency to cause hypercalcemia, new analogs with a better therapeutic profile have been synthesized, including ZK 156718. We compared the effects of 1,25 dihydroxyvitamin D(3) and ZK 156718 on growth, differentiation, and on p21(Waf1/Cip1) and p27(Kip1) expression in human colon cancer cells (Caco-2). Whereas ZK 156718 at the concentration [10(-8) M] was as potent as 10(-6) M 1,25 dihydroxyvitamin D(3) in inducing differentiation and p21(Waf1/Cip1) expression, it was even more effective in inhibiting cell growth and stimulating p27(Kip1) expression than 1,25-dihydroxyvitamin D(3) itself. In summary, our study presents a new and potent vitamin D analog with a decreased metabolic stability, making it useful for the treatment of a diversity of clinical disorders. PMID- 11779201 TI - Regulation of transformed state by calpastatin via PKCepsilon in NIH3T3 mouse fibroblasts. AB - Ca(2+)-activated neutral protease calpain is ubiquitously expressed and may have pleiotropic biological functions. We have previously reported that repeated treatment of NIH3T3 mouse fibroblasts with the calpain inhibitor N-acetyl-Leu-Leu norleucinal (ALLN) resulted in the induction of transformed foci [T. Hiwasa, T. Sawada, and S. Sakiyama (1990) Carcinogenesis 11, 75-80]. To elucidate further the effects of calpain in malignant transformation of NIH3T3 cells, calpastatin, an endogenous specific inhibitor of calpain, was expressed in NIH3T3 cells by transfection with cDNA. G418-selected calpastatin-expressing clones showed a significant increase in the anchorage-independent growth ability. A similar increase in cloning efficiency in soft agar medium was also observed in calpain small-subunit-transfected clones. On the other hand, reduced expression of calpastatin achieved by transfection with calpastatin antisense cDNA in Ha-ras transformed NIH3T3 (ras-NIH) cells caused morphological reversion as well as a decrease in anchorage-independent growth. When NIH3T3 cells were treated with ALLN for 3 days, cell growth was stimulated by approximately 10%. This growth stimulation by ALLN was not observed in ras-NIH cells, but recovered by expression of a dominant negative form of protein kinase C (PKC)epsilon but not by that of PKCalpha. Western blotting analysis showed that an increase in PKCepsilon was much more prominent than that of PKCalpha in NIH3T3 cells after treatment with ALLN. These results are concordant with the notion that calpain suppresses malignant transformation by predominant degradation of PKCepsilon. PMID- 11779202 TI - Messenger RNA profiles in liver injury and stress: a comparison of lethal and nonlethal rat models. AB - Liver damage activates processes aimed at repairing damage; simultaneously, liver functions required for survival must be maintained. The expression of genes responsible for both in rat models of lethal (lipopolysaccharide, 90% hepatectomy, and d-galactosamine) and nonlethal (turpentine, 70% hepatectomy, and acetaminophen) liver damage and stress was measured at 3, 6, 12, and 24 h after the intervention and quantitated as the area between the control curves and the test curves (AUC). The expression of genes for cell division and remodeling was upregulated most in the lethal models. The expression of most liver-specific function genes was reduced. Positive AUC was found for ARG, ASL, CPT1, Mdr1b, Mdr2, and PEPCK. It is concluded that a high expression of genes for repair of liver damage is associated with reduced expression of genes for several liver specific functions, possibly reflecting a limited capacity for transcriptional activity. Maintained or increased expression of selected function genes indicates that the corresponding functions have high priority. The liver sustains metabolic homeostasis ensuring that other organs in the body function normally. Simultaneously, the processes required for the integrity of its own structure and function are maintained as a result of regulated expression of the genes that produce the proteins needed to perform both set of functions. PMID- 11779203 TI - FGF-2 increases colony formation, PTH receptor, and IGF-1 mRNA in mouse marrow stromal cells. AB - FGF-2 stimulates bone formation in vitro and in vivo in rats. However, there are limited studies in mice and no data on the mechanism(s) by which FGF-2 induces bone formation. We assessed whether short-term FGF-2 treatment of marrow stromal cells from young mice would increase alkaline phosphatase-positive (ALP), mineralized colony formation and expression of genes important in osteoblast maturation. Short-term treatment with FGF-2 (0.01-1.0 nM) for the first 3 days of a 14- or 21-day culture period increased the number of ALP mineralized colonies in bone marrow stromal cells. FGF-2 (0.1 nM) increased the mRNAs for type 1 collagen: osteocalcin, runt domain/core binding factor, PTH/PTHR receptor, and insulin-like growth factor 1 (IGF-1) at 14 and 21 days. We conclude that short term FGF-2 treatment enhances osteoblast maturation in vitro. Furthermore, the anabolic effect of FGF-2 may be attributed in part to regulation of IGF-1 in osteoblasts. PMID- 11779204 TI - Differential effect of brefeldin A on the palmitoylation of surfactant protein C proprotein mutants. AB - The surfactant protein C precursor (proSP-C) is palmitoylated on two cysteines adjacent to its transmembrane domain. We showed previously that palmitoylation of proSP-C occurs in a postendoplasmic reticulum compartment and is not affected by the Golgi-disturbing agent brefeldin A (BFA). In contrast, the investigations presented here showed that BFA almost completely abolished palmitoylation of proSP-C mutants that contained alterations in the region between the palmitoylated cysteines and the transmembrane domain, including a Pro 30 to Leu mutant associated with interstitial lung disease. This differential effect of BFA was not caused by differences in the palmitoylation kinetics between wild-type proSP-C and the mutants and was not mimicked by nocodazole and monensin. However, differences between the mutants and wild-type proSP-C in the relative degree of processing suggest that BFA may unmask a difference in routing. This would imply that the amino acids just N-terminal of the transmembrane domain may be important for a proper sorting of proSP-C. PMID- 11779205 TI - Apelin (65-77) activates extracellular signal-regulated kinases via a PTX sensitive G protein. AB - We report here that apelin (65-77) induces activation of extracellular-regulated kinases (ERKs) in Chinese hamster ovary (CHO) cells expressing the msr/apj receptor. This concentration-dependent activation was transient, peaking at 5 min. Pretreatment of CHO cells with pertussis toxin fully abrogated ERK phosphorylation, whereas overexpression of the beta-adrenergic receptor kinase-1 C-terminal fragment did not alter ERK activation. Transfection with a dominant negative mutant of Ras was without effect on ERK activation, whereas an inhibitor of many protein kinase C isoforms, GF109203X, strongly decreased it. These results demonstrate that stimulation of the murine msr/apj receptor promotes ERK activation via the alpha subunit of a pertussis toxin-sensitive protein in a Ras independent pathway. PMID- 11779206 TI - Compact form of DNA induced by DNA-binding protein HU. AB - Interaction of DNA-binding protein HU from Bacillus stearothermophilus (HUBst) with coliphage T2 DNA was investigated by means of a single-duplex DNA chain visualization method using fluorescence microscopy. Fluorescence microscopic images of coliphage T2 DNA molecules were observed as a function of HUBst concentration. The average fluorescence image size of T2 DNA decreased with increase in HUBst concentration to a size comparable to that of a DNA globule induced by polyethylene glycol (PEG) and multivalent cation (MVC). The change to globule-like DNA proceeded gradually and monotonously, in contrast to the coil globule transition of DNA induced by PEG and MVC. The histogram of the fluorescence image length was essentially a single-modal one throughout the process of conformational change. These results indicate that the process of shrinking of DNA from a random coil to a globule-like one is not of a transitional nature. The interaction of HUBst with DNA and the mechanism of shrinkage are concluded to be different from those of PEG-induced and MVC-induced coil-globule transition of DNA. PMID- 11779207 TI - Protein kinase C induces motility of breast cancers by upregulating secretion of urokinase-type plasminogen activator through activation of AP-1 and NF-kappaB. AB - Cell migration is a crucial process in cancer metastasis that does not require extracellular matrix degradation-a characteristic of cell invasion. The urokinase type plasminogen activator (uPA) system is responsible for invasion through uPA enzymatic activity and for migration through the binding of uPA to the uPA receptor (uPAR). Constitutively high levels of uPA are characteristic of the highly metastatic breast cancer cells MDA-MB-231, but the mechanisms underlying constitutive uPA expression are not fully characterized. In this report we show that inhibition of protein kinase C (PKC) represses constitutive (nonstimulated) migration of MDA-MB-231 cells. Bisindolylmaleimide I (Bis I) inhibits cell migration and constitutive activation of transcription factors AP-1 and NF kappaB, suggesting that PKC is responsible for increased migration of MDA-MB-231 cells. It is clear that the inhibition of PKC occurs at the transactivation levels of AP-1 and NF-kappaB because Bis I did not affect constitutive DNA binding of AP-1 and NF-kappaB. Furthermore, we show that Bis I did not affect the levels of IkappaBalpha, suggesting that PKC-mediated cell migration is IkappaBalpha independent. Finally, we demonstrate that constitutive secretion of uPA is repressed by Bis I, implying an important role for AP-1 and NF-kappaB in cell migration. Our data demonstrate a connection among PKC, constitutively active AP-1 and NF-kappaB, constitutive secretion of uPA, and cell migration of highly invasive breast cancer cells. Thus, PKC controls cell motility by regulating expression of uPA through the activation of AP-1 and NF-kappaB. The disruption of PKC, AP- 1, and NF-kappaB signaling in breast cancer may be used to develop therapies for breast cancer prevention and intervention by reducing the secretion of uPA. PMID- 11779208 TI - Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18. AB - P18 (KWKLFKKIPKFLHLAKKF-NH(2)) is an alpha-helical antimicrobial peptide designed from a cecropin A-magainin 2 hybrid. In this study, P18 was found to show strong antimicrobial activity against several antibiotic-resistant bacterial and fungal strains. Both the salt resistance on antimicrobial activity and the synergistic effect with clinically used antibiotic agents are critical factors in developing effective peptide antibiotic drugs. For this reason, we investigated the salt resistance of P18 to antagonism by NaCl, CaCl(2), and MgCl(2) on antimicrobial activity and the synergistic effect of P18 with vancomycin against vancomycin resistant Enterococcus faecium (VREF). Compared to magainin 2, P18 showed strong resistance on antimicrobial activity against bacterial strains and C. albicans under high NaCl concentrations of 100-200 mM. In addition, P18 displayed much greater salt resistance on antibacterial activity against Gram-negative bacteria at the physiological or elevated concentrations of CaCl(2) and MgCl(2) than magainin 2. Furthermore, the combination study revealed that P18 has a relatively effective synergistic effect with vancomycin against VREF. Thus, these results support that P18 may prove to be a salt-resistant antibiotic peptide potentially useful in the treatment of cystic fibrosis patients as well as a valuable adjuvant for antimicrobial chemotherapy. PMID- 11779209 TI - Isolation of a novel agglutinin with complex carbohydrate binding specificity from fresh fruiting bodies of the edible mushroom Lyophyllum shimeiji. AB - A hemagglutinin, with a molecular weight of 30,000 and expressing hemagglutinating activity which could not be inhibited by simple sugars and glycoproteins, was isolated from fresh fruiting bodies of the edible mushroom Lyophyllum shimeiji. The protein was adsorbed on CM-Sepharose even in 20 mM ammonium acetate (pH 5.5) containing 1 M NaCl and was desorbed by 20 mM ammonium bicarbonate (pH 9). The hemagglutinating activity was subsequently adsorbed on Mono S in 20 mM ammonium acetate (pH 5.5) and was desorbed by a linear gradient of 0.2-0.5 M NaCl in ammonium acetate buffer. The hemagglutinin exhibited a novel N-terminal sequence not found in any lectin and hemagglutinin reported so far. It was devoid of antifungal activity. PMID- 11779210 TI - Two novel RNA binding proteins from Trypanosoma brucei are associated with 5S rRNA. AB - We have previously reported the identification of two closely related RNA binding proteins from Trypanosoma brucei which we have termed p34 and p37. The predicted primary structures of the two proteins are highly homologous with one major difference, an 18-amino-acid insert in the N-terminal region of p37. These two proteins have been localized to the nucleus based on immunofluorescence microscopy. To gain insight into their function, we have utilized UV crosslinking, coimmunoprecipitation, and sucrose density gradients to identify T. brucei RNA species that associate with p34 and p37. These experiments have demonstrated a specific interaction of both p34 and p37 with the 5S ribosomal RNA and indicate that other RNA species are unlikely to be specifically bound. This suggests a role for p34 and p37 in the import and/or assembly pathway of T. brucei 5S rRNA in ribosome biogenesis. PMID- 11779211 TI - Effect of pectic oligomers on physiological responses of chilling injury in discs excised from zucchini (Cucurbita pepo L.). AB - The effect of pectic oligomers (OG) on ethylene biosynthesis, electrolyte leakage (EL), and CO(2) production was studied in discs excised from zucchini fruit (Cucurbita pepo L.) and stored at 20 or 2.5 degrees C. At 20 degrees C, OG enhanced ethylene biosynthesis and had a transient effect on decreasing EL, but showed little effect on respiratory rate; both the amount and size of the oligomer were important in changing both ethylene synthesis and EL. At 2.5 degrees C, OG increased both ethylene biosynthesis and respiratory rate with a maximum effect at 100 microg of oligomer and peaking at 6 h; shorter oligomers demonstrated an even greater effect on ethylene biosynthesis, but differences were smaller in respiratory rate. EL at 2.5 degrees C was affected most by 1 microg of OG and by monomeric galacturonic acid, with transient increases that peaked at 8 h. We suggest a signaling role for OG in the early steps of cold acclimation or chilling injury. PMID- 11779212 TI - Specificity role of the streptokinase C-terminal domain in plasminogen activation. AB - Several pathogenic bacteria secrete plasminogen activator proteins. Streptokinase (SKe) produced by Streptococcus equisimilis and staphylokinase secreted from Staphylococcus aureus are human plasminogen activators and streptokinase (SKu), produced by Streptococcus uberis, is a bovine plasminogen activator. Thus, the fusion proteins among these activators can explain the function of each domain of SKe. Replacement of the SKalpha domain with staphylokinase donated the staphylokinase-like activation activity to SKe, and the SKbetagamma domain played a role of nonproteolytic activation of plasminogen. Recombinant SKu also activated human plasminogen by staphylokinase-like activation mode. Because SKu has homology with SKe, the bovine plasminogen activation activities of SKe fragments were checked. SKebetagamma among them had activation activity with bovine plasminogen. This means that the C-terminal domain (gamma-domain) of streptokinase determines plasminogen species necessary for activation and converses the ability of substrate recognition to human species. PMID- 11779213 TI - Biosynthesis of beta-substituted furan skeleton in the lower furanoterpenoids: a model study. AB - Furanoterpenes are widely distributed in the plant kingdom. In this study we have carried out enzymatic synthesis of simple furan compounds from the molecules containing an alpha-isopropylidene ketone unit and the role of cytochrome P450 in this biotransformation has been conclusively established. Eight model compounds (acyclic, monocyclic, and bicyclic, 1-8), having an alpha-isopropylidene ketone unit, were synthesized and incubated with PB-induced rat liver microsomes in the presence of NADPH and O(2). GC-MS and NMR analyses of the product(s) indicated the formation of corresponding furano derivatives (11-18). Cytochrome P450 inhibitors, metyrapone, SKF-525, and carbon monoxide, inhibited the formation of furan (8) to 76, 62, and 97%, respectively. Incubation of dehydrofukinone (7), a naturally occurring terpene, with purified cytochrome P450, NADPH-cytochrome P450 reductase, and dilaurylphosphatidylcholine in the presence of NADPH and O(2) resulted in the formation of 10 and furanodehydrofukinone (19). Based on these observations, we propose one of the probable biosynthetic routes for lower furanoterpenoids in higher plants. PMID- 11779214 TI - A physiochemical mechanism of hemozoin (beta-hematin) synthesis by malaria parasite. AB - Malaria parasite homogenate, the lipid extracts, and an unsaturated fatty acid, linoleic acid, which have been shown to promote beta-hematin formation in vitro, were used to investigate the mechanism of hemozoin biosynthesis, a distinct metabolic function of the malaria parasite. In vitro beta-hematin formation promoted by Plasmodium yoelii homogenate, the lipid extracts, and linoleic acid were blocked by ascorbic acid, reduced glutathione, sodium dithionite, beta mercaptoethanol, dithiothreitol, and superoxide dismutase. Oxidized glutathione did not show any effect. Preoxidized preparations of the lipids extracts or the P. yoelii homogenate failed to catalyze beta-hematin formation. Depletion of oxygen in the reaction mixtures also inhibited the lipid-catalyzed beta-hematin formation. Under the reaction conditions similar to those used for the in vitro beta-hematin formation assay, the antioxidants and reducing agents mentioned above, except the DTT and beta-mercaptoethanol, did not cause degradation of heme. beta-Hematin formation was also inhibited by p-aminophenol, a free radical chain reaction breaker. Hemozoin biosynthesis within the digestive vacuoles of the malaria parasite may be a lipid-catalyzed physiochemical reaction. An oxidative mechanism may be proposed for lipid-mediated beta-hematin formation, which may be mediated by generation of some free radical intermediates of heme. PMID- 11779215 TI - Identification of a novel endothelial-derived gene EG-1. AB - The identification of novel endothelial-derived genes is important in the study of angiogenesis, and may have potential uses in cancer diagnosis and treatment. We performed SSH (suppression subtractive hybridization) on control HUVECs (human umbilical vein endothelial cells) versus HUVECs exposed to tumor-conditioned media. We found that a novel cDNA (GenBank Accession No. AF358829) is differentially expressed in endothelial cells on Northern analysis, and named it endothelial-derived gene-1 (EG-1). This gene product is predicted to encode a 178 aa, 19.5-kDa protein, and is localized to chromosome 4. It has some homology to a mouse cDNA (94%) and a Drosophila cDNA (31%). On Northern analysis, endothelial cells express two EG-1 RNA species (1.2 and 2.4 kb). The expression of either transcripts is upregulated by endothelial cells when exposed to tumor conditioned media. This phenomenon is observed only under sparse conditions (50% confluency). Transcripts are present abundantly in highly vascular tissues such as placenta, testis, and liver. Interestingly, both Northern analysis and in situ hybridization studies show that this gene is expressed in other cell types as well, predominantly the epithelial type. Breast cancer, prostate cancer, and colon cancer cells show elevated expression of the higher 2.4-kb RNA form. Our data suggest that EG-1 is associated with a stimulated state in endothelial and epithelial cells, and may have a role in tumor angiogenesis. PMID- 11779216 TI - Integrins and stretch activated ion channels; putative components of functional cell surface mechanoreceptors in articular chondrocytes. AB - Perception of mechanical signals and the biological responses to such stimuli are fundamental properties of load bearing articular cartilage in diarthrodial joints. Chondrocytes utilize mechanical signals to synthesize an extracellular matrix capable of withstanding high loads and shear stresses. Recent studies have shown that chondrocytes undergo changes in shape and volume in a coordinated manner with load induced deformation of the matrix. These matrix changes, together with alterations in hydrostatic pressure, ionic and osmotic composition, interstitial fluid and streaming potentials are, in turn, perceived by chondrocytes. Chondrocyte responses to these stimuli are specific and well coordinated to bring about changes in gene expression, protein synthesis, matrix composition and ultimately biomechanical competence. In this hypothesis paper we propose a chondrocyte mechanoreceptor model incorporating key extracellular matrix macromolecules, integrins, mechanosensitive ion channels, the cytoskeleton and subcellular signal transduction pathways that maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. PMID- 11779217 TI - Cyclin b1 promoter activity and functional cdk1 complex formation in G1 phase of human breast cancer cells. AB - Overexpression of cyclin B has been detected in various human breast cancer cell lines, breast tumor tissues, and immortalized but nontransformed breast cells. The cause of this overexpression has not been thoroughly investigated, nor is it known if cyclin B protein forms a functional complex with its partner, cdk1, at inappropriate cell cycle periods. In this study we examined the pattern of cyclin B1 promoter activity in three breast cancer cell lines, BT-549, MDA-MB-157, T 47D, and the immortalized breast cell line MCF-10F. Using cells stably transfected with a cyclin B1 promoter-luciferase reporter, luciferase activity was measured throughout the cell cycle in lovastatin synchronized cells and in G1 and S/G2 phases of asynchronized cells by flow cytometry. Results demonstrate that the cyclin B1 promoter activity increases, as expected, during the S/G2 period in all the cell lines. However, some promoter activity can be detected in G1 phase of the different cell line with BT-549 displaying the more altered pattern. Functional cyclin B1-cdk 1 protein complex was detected in G1 phase of BT-549 and T-47D cell lines. These results suggest that in a subset of transformed breast cancer cells altered cyclin B1 promoter activity may contribute to the misexpression of cyclin B protein. PMID- 11779218 TI - The number of secretory vesicles remains unchanged following exocytosis. AB - Earlier studies using electron microscopy demonstrate that there is no loss of secretory vesicles following exocytosis. Depletion however, of vesicular contents resulting in the formation of empty or partially empty vesicles is seen in electron micrographs, post exocytosis, in a variety of cells. Our studies using atomic force microscopy (AFM) reveal that following stimulation of secretion, live pancreatic acinar cells having 100-180 nm in diameter fusion pores located at the apical plasma membrane, dilate only 25-35% during exocytosis. Since secretory vesicles in pancreatic acinar cells range in size from 200 nm to 1200 nm in diameter, their total incorporation at the fusion pore, would distend the structure much more then what is observed. These earlier results prompted the current study to determine secretory vesicle dynamics in live pancreatic acinar cells following exocytosis. AFM studies on live acinar cells reveal no loss of secretory vesicle number following exocytosis. Parallel studies using electron microscopy, further confirmed our AFM results. These studies demonstrate that following stimulation of secretion, membrane-bound secretory vesicles transiently dock and fuse to release vesicular contents. PMID- 11779219 TI - Structure and dynamics of the fusion pore in live cells. AB - Atomic force microscopy reveal pit-like structures typically containing three or four, approximately 150 nm in diameter depressions at the apical plasma membrane in live pancreatic acinar cells. Stimulation of secretion causes these depressions to dilate and return to their resting size following completion of the process. Exposure of acinar cells to cytochalasin B results in decreased depression size and a loss in stimulable secretion. It is hypothesized that depressions are the fusion pores, where membrane-bound secretory vesicles dock and fuse to release vesicular contents. Zymogen granules, the membrane-bound secretory vesicles in exocrine pancreas, contain the starch digesting enzyme, amylase. Using amylase-specific immunogold labeling, localization of amylase at depressions following stimulation of secretion is demonstrated. This study confirms depressions to be the fusion pores in pancreatic acinar cells. High resolution images of the fusion pore in live pancreatic acinar cells reveal the structure in much greater detail than has previously been observed. PMID- 11779220 TI - CD14-dependent activation of NF-kappaB by filarial parasitic sheath proteins. AB - Tropical pulmonary eosinophilia is in part caused by the hyperimmune responsiveness of the lung tissue against the antigens of degenerating microfilariae. We have previously shown that the activation of the transcription factor NF-kappaB is essential for the synthesis and release of multiple pro inflammatory cytokines in HEp-2 human airway epithelial cells following exposure to filarial parasitic sheath proteins (FPS). Neither the antigenic component nor the receptor involved in this activation is known. Herein we provide evidence that FPS activation of NF-kappaB can be augmented by the cell surface expression of CD14. CD14 expression, however, is not sufficient to transduce FPS signals for NF-kappaB activation, since its expression in different cell types does not always furnish the capacity to respond to FPS. We also show that NF-kappaB activation by FPS treatment can be distinguished from that induced by bacterial lipolysaccharide, an agent that can also activate NF-kappaB in a CD14-dependent fashion. These observations suggest that the capacity of certain lung epithelial cells to interact with microfilarial antigens, activate NF-kappaB in a CD14 dependent manner and produce pro-inflammatory cytokines may be a contributory factor to immune responses manifested by tropical pulmonary eosinophilia. PMID- 11779221 TI - Direct chemotactic effect of bradykinin and related peptides-significance of amino- and carboxyterminal character of oligopeptides in chemotaxis of tetrahymena pyriformis. AB - The chemotactic character of the nonapeptide bradykinin (BK1-9) and its derivatives was studied in the eukaryotic ciliated model Tetrahymena pyriformis. The results demonstrate that BK1-9 has a direct and ligand-specific chemoattractant effect (maximal at 10(-11) m) without any intermediate substance as is essential in some mammalian test systems. Evaluation of the chemotactic effect elicited by derivatives showed that the presence of N- and C-terminal arginines can influence chemotactic potency of the molecule via expression of pyrrolidine and aromatic ring structures of terminal amino acid residues. Removal of the N-terminal Arg (expression of Pro) results in a significant decrease in chemotaxis (BK2-9), while further truncation of the C-terminal, causing expression of the aromatic ring of Phe (BK2-8), results in a highly chemoattractant variant. A single pyrrolidine ring on the C-terminus BK1-7 also has a positive effect on the chemotactic character, however further truncation (BK1-6, BK1-5) causes the chemoattractant character to become chemorepellent. Study of chemotactic selection with BK derivatives supports our previous findings that only phylogenetically selected ligands or their close derivatives are able to induce long-term selection with chemotaxis. PMID- 11779222 TI - Antigenic and ultrastructural markers associated with urothelial cytodifferentiation in primary explant outgrowths of mouse bladder. AB - The purpose of this study was to establish an in vitro culture model that closely resembles whole mouse urothelial tissue. Primary explant cultures of mouse bladder were established on porous membrane supports and explant outgrowths were analysed for morphology and the presence of antigenic and ultrastructural markers associated with urothelial cytodifferentiation. When examined at the ultrastructural level, the cultured urothelium was polarized and organized as a multilayered epithelium. Differentiation was found to increase from the porous membrane towards the surface and from the explant towards the periphery of the culture. Scanning and transmission electron microscopical analysis of the most superficially-located cells revealed four successive differentiation stages: cells with microvilli, cells with ropy microridges, cells with rounded microridges, and highly-differentiated cells with asymmetric unit membrane (AUM) plaques forming rigid microridges and fusiform vesicles. The more highly differentiated cells were numerous at the periphery of the culture, but rare close to the explant. Epithelial organization was stabilized by well developed cell junctions. Immunolabeling demonstrated that superficial urothelial cells in culture: (1) develop tight junctions, E-cadherin adherens junctions and abundant desmosomes and (2) express uroplakins and cytokeratin 20 (CK 20). Using a culture model of primary explant outgrowth we have shown that non-differentiated mouse urothelial cells growing on a porous membrane show a high level of de novo differentiation. PMID- 11779223 TI - FK506 enhanced osteoblastic differentiation in mesenchymal cells. AB - Bone morphogenetic protein (BMP) is a bone-derived growth factor capable of promoting the differentiation of mesenchymal cells into osteogenic lineage pathways. Recently, immunosuppressants were reported to cause a moderate increase in osteoblastic differentiation in a rat osteoblast-like osteosarcoma cell line. If immunosuppressants can induce osteoblastic differentiation, it will be useful for bone tissue transplantation. We assessed the effect of immunosuppressants with or without BMP-4 on inducing osteoblastic differentiation in osteoblast-like and other mesenchymal cells. FK506, an immunosuppressant often used clinically, induced a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, one of the markers of osteoblast differentiation, in cells derived from mesenchyma. In the presence of BMP-4, ALP activity, mRNA levels of ALP and osteocalcin increased. FK506 was found to not only stimulate osteoblastic differentiation, but also to enhance BMP-4 induced osteoblastic differentiation. These results suggest that FK506 promotes differentiation of osteoblastic cells. PMID- 11779224 TI - Mitogenic stimulation in isoproterenol treated cells of dictyostelium discoideum. AB - Amoebae of the cellular slime mould Dictyostelium discoideum showed stimulated mitogenic activity when exposed to 200 microM isoproterenol, an activator of adenyl cyclase, for 30 min. Approximately 40% increase in cell proliferation was found at 48 h after isoproterenol treatment. A faster and larger plaque formation as well as higher uptake of FITC-labelled E. coli indicates greater phagocytotic activity in the treated cells. A concurrent increase in DNA and protein syntheses was also recorded in the treated cells. Administration of 400 microM caffeine or 200 microM (+) propranolol brought down the isoproterenol-induced elevation in the cell division rate to control levels. These results are discussed in relation to a precocious activation of adenyl cyclase in the treated cells leading to a transient but significant increase in cell division in this organism. PMID- 11779225 TI - Mosquito larvae soluble fractions induce DNA synthesis alterations on human mononuclear cells. AB - Mosquito larvae soluble fractions obtained by molecular exclusion chromatography altered the mitotic rate of several epithelial cell populations in hepatectomised mice, as well as the proliferation of human mononuclear cells (MNC), stimulating or inhibiting them depending on the fraction and dose applied. The effect was also thermolabile, suggesting a proteic nature of the compounds involved. Analysis of cell viability after culture indicated that the extract did not have lethal toxic effects. One fraction with a molecular weight ranging between 12-80 kDa caused only an inhibitory effect. In the present study, we performed further characterisation of this fraction by assaying the effect of new fractions obtained from this one, by the use of a column with a lower molecular weight exclusion range. Assays were performed on the proliferation of adult human MNCs. Our results showed that two out of four of the sub-fractions analysed, with a MW of about 70 and 17 kDa, caused a dose-dependent response, either inhibiting or stimulating MNC proliferation respectively. PMID- 11779226 TI - GTP-binding proteins G(salpha), G(ialpha), and Ran identified in mitochondria of human placenta. AB - GTP-binding proteins (GTPases) have been detected in the mitochondria of human placenta. It has been proposed that porin interacts with GTPases in the mitochondrion to modulate contact site function, however, their identity and location is not known. In this study, we investigated the location of GTPases in mitochondria from term placentae as well as the expression of mitochondrial GTPases in mid-term placentae. Mitochondria obtained from human term and mid-term placentae were purified by sedimentation. Sub-mitochondrial vesicles prepared from ruptured and sonicated mitochondria were separated by ultracentrifugation in sucrose density gradients. The location of membrane vesicles was determined using marker enzymes. Mitochondrial proteins were separated by SDS-PAGE. Western blots were incubated in [alpha-(32)P]-GTP and detected using autoradiography or antibodies against known GTPases and porin followed by enhanced chemiluminescence. [alpha-(32)P]-GTP bound 24 and 28 kDa proteins located in the outer membrane. The G(salpha)antibody detected 42.5, 53 and 67 kDa proteins. The G(ialpha)antibody identified a 40.5 kDa band in contact sites and the outer membrane, as well as 55 and 105 kDa proteins in contact site vesicles. The Ran antibody detected a 28 kDa protein, mainly in the outer membrane. Porin migrated at 30 kDa. G(ialpha)and Ran were detected in mitochondria from both term and mid term placentae. The location of porin and GTPases leave open the possibility that these proteins interact in contact sites and may also be responding to extra mitochondrial signals. Ran and G(ialpha)are expressed by mid-term in human placentae and may be necessary for placental functions at this stage of development. It will be important in future experiments to characterise the physiological functions of these GTP-binding proteins in the mitochondria of human placenta. PMID- 11779227 TI - Characterization of proteins associated with heat shock protein hsp27 in the squamous cell carcinoma cell line A431. AB - Heat shock protein hsp27 is a molecular chaperone and identification of hsp27 binding proteins might help to elucidate its functional role in keratinocyte biology. In the present investigation we used a human epidermal cell carcinoma cell line (A431) transfected with hsp27 (A431/16) to study interference between hsp27 protein and other proteins. Immunoprecipitation experiments with anti-hsp27 antibody revealed a multicomponent complex when analysed by silver staining. By immunoblotting analysis we could demonstrate that hsp27 associates with actin, the mutant form of p53, hsp70 and hsp90. Immunofluorescence analysis showed a co localization between hsp27 and p53, hsp70 and hsp90. To control for the specificity of the observed interactions, immuno-precipitations with antibodies to actin, p53, hsp70 and hsp90 respectively, were performed. All of the tested proteins demonstrated a coimmunoprecipitation with hsp27. We conclude that hsp27, like the other heat shock proteins, is part of a complex system of molecular chaperones in epidermal keratinocytes. PMID- 11779228 TI - Androgen dependent expression of AT1 receptor and its regulation of anion secretion in rat epididymis. AB - Our previous studies have provided solid evidence for the presence of an intrinsic angiotensin-generating system in the rat epididymis, which plays an important role in the regulation of the anion and thus fluid secretion by the epididymal epithelium. In the present study, the effect of androgen on the expression of AT(1)receptor and its subsequent regulation of anion secretion by the epididymis were investigated using Western blotting, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in vitro electrophysiological approaches. Results from Western blotting analysis showed that the expression of AT(1)receptor protein was almost abolished by castration whereas its expression was completely restored to the control level when the castrated rats were hormonally replaced with testosterone. Efferent duct ligation, however, appeared not to affect the expression of AT(1)receptor protein by the epididymis. Results from RT-PCR showed that mRNA expression of AT(1)receptor was consistent with that observed in protein expression. Results from short-circuit current (I(SC)) showed that castration almost abolished the angiotensin II-induced I(SC). However, efferent duct ligation did not affect the angiotensin II-induced I(SC), which was completely blocked in the presence of losartan, a specific antagonist of the AT(1)receptor. These data indicate that the expression of epididymal AT(1)receptor is predominantly influenced by testicular androgens but not by testicular factors. This androgen-dependent expression of AT(1)receptor could have a role in the control of AT(1)receptor mediated anion secretion and thus fluid secretion by the rat epididymis. PMID- 11779229 TI - Mitotic activity of the duodenal crypt enterocytes in mice transplanted with EA21a mammary carcinoma. AB - The presence of a tumor generally changes the mitotic activity of the normal cell population in mice. In the present work, the mitotic activity of the duodenal crypt enterocytes in EA21a mammary carcinoma-bearing mice was determined. The results show that there is a patent circadian variation in normal mice and, in the presence of the EA21a mammary tumor, cell proliferation is stimulated. Stimulation was evident in enterocytes from the intermediate as well as the superficial regions of the crypt. Some humoral factors produced by the transplanted tumor could interfere with the regulatory mechanism of the mitotic activity of duodenal crypt enterocytes. PMID- 11779230 TI - Concerted motions in HIV-1 TAR RNA may allow access to bound state conformations: RNA dynamics from NMR residual dipolar couplings. AB - Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using recently introduced NMR methods that rely on the measurement of residual dipolar couplings (RDC) in partially oriented systems. Order matrix analysis of RDC data provides evidence for inter-helical motions that are of amplitude 46(+/ 4) degrees, of random directional character, and that are executed about an average conformation with an inter-helical angle between 44 degrees and 54 degrees. The generated ensemble of TAR conformations have different organizations of functional groups responsible for interaction with the trans-activator protein Tat, including conformations similar to the previously characterized bound-state conformation. These results demonstrate the utility of RDC-NMR for simultaneously characterizing RNA tertiary dynamics and average conformation, and indicate an avenue for TAR complex formation involving tertiary structure capture. PMID- 11779231 TI - Non-standard insulin design: structure-activity relationships at the periphery of the insulin receptor. AB - The design of insulin analogues has emphasized stabilization or destabilization of structural elements according to established principles of protein folding. To this end, solvent-exposed side-chains extrinsic to the receptor-binding surface provide convenient sites of modification. An example is provided by an unfavorable helical C-cap (Thr(A8)) whose substitution by favorable amino acids (His(A8) or Arg(A8)) has yielded analogues of improved stability. Remarkably, these analogues also exhibit enhanced activity, suggesting that activity may correlate with stability. Here, we test this hypothesis by substitution of diaminobutyric acid (Dab(A8)), like threonine an amino acid of low helical propensity. The crystal structure of Dab(A8)-insulin is similar to those of native insulin and the related analogue Lys(A8)-insulin. Although no more stable than native insulin, the non-standard analogue is twice as active. Stability and affinity can therefore be uncoupled. To investigate alternative mechanisms by which A8 substitutions enhance activity, multiple substitutions were introduced. Surprisingly, diverse aliphatic, aromatic and polar side-chains enhance receptor binding and biological activity. Because no relationship is observed between activity and helical propensity, we propose that local interactions between the A8 side-chain and an edge of the hormone-receptor interface modulate affinity. Dab(A8)-insulin illustrates the utility of non-standard amino acids in hypothesis driven protein design. PMID- 11779232 TI - Loop-inserted and thermostabilized structure of P1-P1' cleaved ovalbumin mutant R339T. AB - Ovalbumin is a member of a superfamily of serine proteinase inhibitors, known as the serpins. It is, however, non-inhibitory towards serine proteinases, and lacks the loop insertion mechanism common to the serpins due to unknown structural factors. Mutant ovalbumin, R339T, in which the P14 hinge residue is replaced, was produced and analyzed for its thermostability and three-dimensional structure. Differential scanning calorimetry revealed that the mutant ovalbumin, but not the wild-type protein, undergoes a marked thermostabilization (DeltaT(m)=15.8 degrees C) following the P1-P1' cleavage. Furthermore, the crystal structure, solved at 2.3 A resolution, clearly proved that the P1-P1' cleaved form assumes the fully loop-inserted conformation as seen in serpin that possess inhibitory activity. We therefore conclude that ovalbumin acquires the structural transition mechanism into the loop-inserted, thermostabilized form by the single hinge mutation. The mutant protein does not, however, possess inhibitory activity. The solved structure displays the occurrence of specific interactions that may prevent the smooth motion, relative to sheet A, of helices E and F and of the loop that follows helix F. These observations provide crucial insights into the question why R339T is still non-inhibitory. PMID- 11779233 TI - A pH-dependent conformational change, rather than the chemical step, appears to be rate-limiting in the hammerhead ribozyme cleavage reaction. AB - We have investigated the chemical basis for a previously observed 7.8 A conformational change in the hammerhead ribozyme that positions the substrate for in-line attack. We have found that the conformational change can only be observed at or above pH 8.5 (in the presence of Co(2+)) and requires the presence of an ionizable 2'-OH at the cleavage site, and note that this observed apparent pK(a) of 8.5 for the conformational change is within experimental error (+/-0.5) of the previously reported apparent kinetic pK(a) of 8.5 for the hammerhead ribozyme in the presence of Co(2+). We have solved two crystal structures of hammerhead ribozymes having 2'-OCH(3) or 2'-F substitutions at the cleavage site and have found that these will not undergo a conformational change equivalent to that observed for the hammerhead ribozyme having an unmodified attacking nucleophile under otherwise identical conditions. We have also characterized the kinetics of cleavage in the crystal. In addition to verifying that the particular sequence of RNA that we crystallized cleaves faster in the crystal than in solution, we also find that the extent of cleavage in the crystal is complete, unlike in solution where this and most other hammerhead ribozyme substrates are cleaved only to about 70 % completion. The initial cleavage rate in the crystal obeys the expected log-linear relation between cleavage-rate and pH with a slope of 0.7, as has been observed for other hammerhead ribozyme sequences in solution, indicating that in both the crystal and in solution the pH-dependent step is rate-limiting. However, the cleavage rate in the crystal is biphasic, with the most dramatic distinction between initial (slower) and final (faster) phases appearing at pH 6.0. The initial phase corresponds to the pH-dependent cleavage rate observed in solution, but the second, faster phase is roughly pH-independent and closely parallels the cleavage rate observed at pH 8 (0.4/minute). This result is particularly remarkable because it entails that the rapidly cleaving phase at pH 6 is comparable to the cleavage rate for the fastest cleaving hammerhead ribozymes at pH 6. Based upon these observations, we conclude that the pH dependent conformational change is the rate-determining step under standard conditions for the hammerhead ribozyme self-cleavage reaction, and that an ionizable 2'-proton at cleavage site is required for this conformational change. We further hypothesize that deprotonation of the cleavage-site 2'-oxygen drives this conformational change. PMID- 11779234 TI - A functional role for a flexible loop containing Glu182 in the class II fructose 1,6-bisphosphate aldolase from Escherichia coli. AB - Class II fructose 1,6-bisphosphate aldolases (FBP-aldolases) catalyse the zinc dependent, reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP). Analysis of the structure of the enzyme from Escherichia coli in complex with a transition state analogue (phosphoglycolohydroxamate, PGH) suggested that substrate binding caused a conformational change in the beta5-alpha7 loop of the enzyme and that this caused the relocation of two glutamate residues (Glu181 and Glu182) into the proximity of the active site. Site-directed mutagenesis of these two glutamate residues (E181A and E182A) along with another active site glutamate (Glu174) was carried out and the mutant enzymes characterised using steady-state kinetics. Mutation of Glu174 (E174A) resulted in an enzyme which was severely crippled in catalysis, in agreement with its position as a zinc ligand in the enzyme's structure. The E181A mutant showed the same properties as the wild-type enzyme indicating that the residue played no major role in substrate binding or enzyme catalysis. In contrast, mutation of Glu182 (E182A) demonstrated that Glu182 is important in the catalytic cycle of the enzyme. Furthermore, the measurement of deuterium kinetic isotope effects using [1(S)-(2)H]DHAP showed that, for the wild-type enzyme, proton abstraction was not the rate determining step, whereas in the case of the E182A mutant this step had become rate limiting, providing evidence for the role of Glu182 in abstraction of the C1 proton from DHAP in the condensation direction of the reaction. Glu182 lies in a loop of polypeptide which contains four glycine residues (Gly176, Gly179, Gly180 and Gly184) and a quadruple mutant (where each glycine was converted to alanine) showed that flexibility of this loop was important for the correct functioning of the enzyme, probably to change the microenvironment of Glu182 in order to perturb its pK(a) to a value suitable for its role in proton abstraction. These results highlight the need for further studies of the dynamics of the enzyme in order to fully understand the complexities of loop closure and catalysis in this enzyme. PMID- 11779235 TI - Crystal structure analysis of the exocytosis-sensitive phosphoprotein, pp63/parafusin (phosphoglucomutase), from Paramecium reveals significant conformational variability. AB - During exocytosis of dense-core secretory vesicles (trichocysts) in Paramecium, the protein pp63/parafusin (pp63/pf) is transiently dephosphorylated. We report here the structures of two crystal forms of one isoform of this protein which has a high degree of homology with rabbit phosphoglucomutase, whose structure has been reported. As expected, both proteins possess highly similar structures, showing the same four domains forming two lobes with an active-site crevice in between. The two X-ray structures that we report here were determined after crystallization in the presence of sulfate and tartrate, and show the lobes arranged as a closed and an open conformation, respectively. While both conformations possess a bound divalent cation, only the closed (sulfate-bound) conformation shows bound sulfate ions in the "phosphate-transfer site" near the catalytic serine residue and in the "phosphate-binding site". Comparison with the open form shows that the latter dianion is placed in the centre of three arginine residues, one contributed by subunit II and two by subunit IV, suggesting that it causes a contraction of the arginine triangle, which establishes the observed conformational closure of the lobes. It is therefore likely that the closed conformation forms only when a phosphoryl group is bound to the phosphate-binding site. The previously published structure of rabbit phosphoglucomutase is intermediate between these two conformers. Several of the known reversible phosphorylation sites of pp63/pf-1 are at positions critical for transition between the conformations and for binding of the ligands and thus give hints as to possible roles of pp63/pf-1 in the course of exocytosis. PMID- 11779236 TI - A novel view of domain flexibility in E. coli adenylate kinase based on structural mode-coupling (15)N NMR relaxation. AB - Adenylate kinase from Escherichia coli (AKeco), consisting of a single 23.6 kDa polypeptide chain folded into domains CORE, AMPbd and LID, catalyzes the reaction AMP+ATP-->2ADP. In the ligand-free enzyme the domains AMPbd and LID execute large amplitude movements controlling substrate binding and product release during catalysis. Domain flexibility is investigated herein with the slowly relaxing local structure (SRLS) model for (15)N relaxation. SRLS accounts rigorously for coupling between the global and local N-H motions through a local ordering potential exerted by the protein structure at the N-H bond. The latter reorients with respect to its protein surroundings, which reorient on the slower time scale associated with the global protein tumbling. AKeco diffuses globally with correlation time tau(m)=15.1 ns, while locally two different dynamic cases prevail. The domain CORE features ordering about the equilibrium N-H bond orientation with order parameters, S(2), of 0.8-0.9 and local motional correlation times, tau, mainly between 5-130 ps. This represents a conventional rigid protein structure with rapid small-amplitude N-H fluctuations. The domains AMPbd and LID feature small parallel (Z(M)) ordering of S(2)=0.2-0.5 which can be reinterpreted as high perpendicular (Y(M)) ordering. M denotes the local ordering/local diffusion frame. Local motion about Z(M) is given by tau( parallel) approximately 5 ps and local motion of the effective Z(M) axis about Y(M) by tau( perpendicular)=6-11 ns. Z(M) is tilted at approximately 20 degrees from the N-H bond. The orientation of the Y(M) axis may be considered parallel to the C(alpha)(i-1)-C(alpha)(i) axis. The tau( perpendicular) mode reflects collective nanosecond peptide-plane motions, interpretable as domain motion. A powerful new model of protein flexibility/domain motion has been established. Conformational exchange (R(ex)) processes accompany the tau( perpendicular) mode. The SRLS analysis is compared with the conventional model-free analysis. PMID- 11779237 TI - A novel main-chain anion-binding site in proteins: the nest. A particular combination of phi,psi values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions. AB - Main-chain conformations where one amino acid residue can be described as gamma(R) (or alpha(R)) and an adjacent one as gamma(L) (or alpha(L)) mostly result in the three main-chain NH groups (of the two residues and the one following) forming a depression that can accommodate an atom with a whole or partial negative charge. We propose the name nest for this feature. The negatively charged atom, when present, is also stabilized by hydrogen-bonding with the NH groups. In an average protein, 8 % of residues are involved in a nest. The anion, or partially negatively charged atom, that often occupies the nest may be a main-chain carbonyl oxygen atom as in the paperclip, also called the Schellman loop, and the oxyanion hole of serine proteases. It can be a phosphate group, as in the P-loop superfamily that binds ATP and GTP. Overlapping, compound, nests are observed often, as in the P-loop, which has five successive NH groups that bind the beta phosphate group of nucleotide triphosphate. The longest compound nests are found surrounding cysteine-bound [2Fe2S] and [4Fe4S] iron-sulfur centers, which are also anionic; nests may encourage binding of the more reduced forms. The nest is a novel feature in the sense of not having been described as a unique motif with anion-binding potential before, although some of the situations where it occurs are familiar. PMID- 11779238 TI - The conformations of polypeptide chains where the main-chain parts of successive residues are enantiomeric. Their occurrence in cation and anion-binding regions of proteins. AB - We have investigated the shapes of polypeptides where successive residues have main-chain phi,psi conformations of opposite hand. A graph not unlike a Ramachandran plot is presented illustrating the various possible conformations. All are ring-shaped or extended. Some of these conformations occur in native proteins, the commonest approximating to a feature we propose calling a nest, described in the accompanying paper, where the main-chain NH groups point inwards relative to the ring and give rise to an anion-binding site. Another conformation is related but more extended and is found uniquely in the four stretches of polypeptide that line the tetrameric K(+) channel; their CO groups bind the K ions in the channel. In a different ring-shaped conformation that we propose calling a catgrip, the main-chain CO groups point into the ring; this is employed for specific Ca ion binding in the annexin, phospholipase A2 and subtilisin loops, and the regularly arranged beta-roll loops of the serralysin protease family. PMID- 11779239 TI - Highly divergent dihydrofolate reductases conserve complex folding mechanisms. AB - To test the hypothesis that protein folding mechanisms are better conserved than amino acid sequences, the mechanisms for dihydrofolate reductases (DHFR) from human (hs), Escherichia coli (ec) and Lactobacillus casei (lc) were elucidated and compared using intrinsic Trp fluorescence and fluorescence-detected 8-anilino 1-naphthalenesulfonate (ANS) binding. The development of the native state was monitored using either methotrexate (absorbance at 380 nm) or NADPH (extrinsic fluorescence) binding. All three homologs displayed complex unfolding and refolding kinetic mechanisms that involved partially folded states and multiple energy barriers. Although the pairwise sequence identities are less than 30 %, folding to the native state occurs via parallel folding channels and involves two types of on-pathway kinetic intermediates for all three homologs. The first ensemble of kinetic intermediates, detected within a few milliseconds, has significant secondary structure and exposed hydrophobic cores. The second ensemble is obligatory and has native-like side-chain packing in a hydrophobic core; however, these intermediates are unable to bind active-site ligands. The formation of the ensemble of native states occurs via three channels for hsDHFR, and four channels for lcDHFR and ecDHFR. The binding of active-site ligands (methotrexate and NADPH) accompanies the rate-limiting formation of the native ensemble. The conservation of the fast, intermediate and slow-folding events for this complex alpha/beta motif provides convincing evidence for the hypothesis that evolutionarily related proteins achieve the same fold via similar pathways. PMID- 11779240 TI - Folding of the yeast prion protein Ure2: kinetic evidence for folding and unfolding intermediates. AB - The Saccharomyces cerevisiae non-Mendelian factor [URE3] propagates by a prion like mechanism, involving aggregation of the chromosomally encoded protein Ure2. The N-terminal prion domain (PrD) of Ure2 is required for prion activity in vivo and amyloid formation in vitro. However, the molecular mechanism of the prion like activity remains obscure. Here we measure the kinetics of folding of Ure2 and two N-terminal variants that lack all or part of the PrD. The kinetic folding behaviour of the three proteins is identical, indicating that the PrD does not change the stability, rates of folding or folding pathway of Ure2. Both unfolding and refolding kinetics are multiphasic. An intermediate is populated during unfolding at high denaturant concentrations resulting in the appearance of an unfolding burst phase and "roll-over" in the denaturant dependence of the unfolding rate constants. During refolding the appearance of a burst phase indicates formation of an intermediate during the dead-time of stopped-flow mixing. A further fast phase shows second-order kinetics, indicating formation of a dimeric intermediate. Regain of native-like fluorescence displays a distinct lag due to population of this on-pathway dimeric intermediate. Double-jump experiments indicate that isomerisation of Pro166, which is cis in the native state, occurs late in refolding after regain of native-like fluorescence. During protein refolding there is kinetic partitioning between productive folding via the dimeric intermediate and a non-productive side reaction via an aggregation prone monomeric intermediate. In the light of this and other studies, schemes for folding, aggregation and prion formation are proposed. PMID- 11779241 TI - Critical role of helix 12 of the vitamin D(3) receptor for the partial agonism of carboxylic ester antagonists. AB - The carboxy-terminal alpha-helix of a nuclear receptor ligand-binding domain (LBD), helix 12, contains a critical, ligand-modulated interface for the interaction with coactivator proteins. In this study, using the example of the vitamin D receptor (VDR) and the partial antagonist ZK159222, the role of helix 12 (residues 417-427) for both antagonistic and agonistic receptor actions was investigated. Amino acid residue G423 was demonstrated to be critical for partial agonism of ZK159222, but not for the activity of the natural VDR agonist, 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)). The amount of partial agonism of ZK159222 increased when helix 12 was truncated by the last four amino acid residues (Delta424-27) and augmented even more, when in addition helix 12 of VDR's dimerization partner, retinoid X receptor (RXR), was truncated. In contrast, the low agonism of a structural derivative of ZK159222, ZK168281, was not affected comparably, whereas other close structural relatives of ZK159222 even demonstrated the same agonistic activity as that of 1alpha,25(OH)(2)D(3). The amount of agonism of ZK159222 and ZK168281 at different variations of helix 12 correlated well with VDR's ability to complex with coactivator proteins and inversely correlated with the strength of the compound's antagonistic action on 1alpha,25(OH)(2)D(3) signalling. Molecular dynamics simulations of the LBD complexed with the two antagonists could explain their different action by demonstrating a more drastic displacement of helix 12 through ZK168281 than through ZK159222. Moreover, the modelling could indicate a kink of helix 12 at amino acid residue G423, which provides the last four amino acid residues of helix 12 with a modulatory role for the partial agonism of some VDR antagonists, such as ZK159222. In conclusion, partial agonism of a VDR antagonist is lower the more it disturbs helix 12 in taking the optimal position for coactivator interaction. PMID- 11779243 TI - A piece of my mind. The morning after. PMID- 11779245 TI - Research yields clues to improving cell therapy for Parkinson disease. PMID- 11779242 TI - Geminate rebinding in trehalose-glass embedded myoglobins reveals residue specific control of intramolecular trajectories. AB - It is becoming increasingly apparent that hydrophobic cavities (also referred to as xenon cavities) within proteins have significant functional implications. The potential functional role of these cavities in modulating the internal dynamics of carbon monoxide in myoglobin (Mb) is explored in the present study by using glassy matrices derived from trehalose to limit protein dynamics and to eliminate ligand exchange between the solvent and the protein. By varying the temperature ( 15 to 65 degrees C) and humidity for samples of carbonmonoxy myoglobin embedded in trehalose-glass, it is possible to observe a hierarchy of distinct geminate recombination phases that extend from nanosecond to almost seconds that can be directly associated with rebinding from specific hydrophobic cavities. The use of mutant forms of Mb reveals the role of key residues in modulating ligand access between these cavities and the distal hemepocket. PMID- 11779246 TI - Raising health care quality: process, measures, and system failure. PMID- 11779250 TI - Ramipril and risk of diabetes. PMID- 11779251 TI - Ramipril and risk of diabetes. PMID- 11779253 TI - Are weekly courses of antenatal steroids beneficial or dangerous? PMID- 11779254 TI - Are weekly courses of antenatal steroids beneficial or dangerous? PMID- 11779255 TI - Are weekly courses of antenatal steroids beneficial or dangerous? PMID- 11779257 TI - Cost-effectiveness of homocysteine-lowering therapy to prevent coronary heart disease. PMID- 11779258 TI - Cost-effectiveness of homocysteine-lowering therapy to prevent coronary heart disease. PMID- 11779259 TI - Cost-effectiveness of homocysteine-lowering therapy to prevent coronary heart disease. PMID- 11779261 TI - Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. AB - CONTEXT: Little is known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcomes. OBJECTIVE: To investigate whether the association between maternal cigarette smoking and infant birth weight differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 1998-2000 among 741 mothers (174 ever smokers and 567 never smokers) who delivered singleton live births at Boston Medical Center. A total of 207 cases were preterm or low-birth-weight infants and 534 were non-low-birth-weight, full-term infants (control). MAIN OUTCOME MEASURE: Birth weight, gestation, fetal growth by smoking status and CYP1A1 MspI (AA vs Aa and aa, where Aa and aa were combined because of small numbers of aa and similar results), and GSTT1 (present vs absent) genotypes. RESULTS: Without consideration of genotype, continuous maternal smoking during pregnancy was associated with a mean reduction of 377 g (SE, 89 g) in birth weight (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7). When CYP1A1 genotype was considered, the estimated reduction in birth weight was 252 g (SE, 111 g) for the AA genotype group (n = 75; OR, 1.3; 95% CI, 0.6-2.6), but was 520 g (SE, 124 g) for the Aa/aa genotype group (n = 43 for Aa, n = 6 for aa; OR, 3.2; 95% CI, 1.6-6.4). When GSTT1 genotype was considered, the estimated reduction in birth weight was 285 g (SE, 99 g) (OR, 1.7; 95% CI, 0.9-3.2) and 642 g (SE, 154 g) (OR, 3.5; 95% CI, 1.5-8.3) for the present and absent genotype groups, respectively. When both CYP1A1 and GSTT1 genotypes were considered, the greatest reduction in birth weight was found among smoking mothers with the CYP1A1 Aa/aa and GSTT1 absent genotypes (-1285 g; SE, 234 g; P<.001). Among never smokers, genotype did not independently confer an adverse effect. A similar pattern emerged in analyses stratified by maternal ethnicity and in analyses for gestation. CONCLUSIONS: In our study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking. PMID- 11779262 TI - National trends in the outpatient treatment of depression. AB - CONTEXT: Recent advances in pharmacotherapy and changing health care environments have focused increased attention on trends in outpatient treatment of depression. OBJECTIVE: To compare trends in outpatient treatment of depressive disorders in the United States in 1987 and 1997. DESIGN AND SETTING: Analysis of service utilization data from 2 nationally representative surveys of the US general population, the 1987 National Medical Expenditure Survey (N = 34 459) and the 1997 Medical Expenditure Panel Survey (N = 32 636). PARTICIPANTS: Respondents who reported making 1 or more outpatient visits for treatment of depression during that calendar year. MAIN OUTCOME MEASURES: Rate of treatment, psychotropic medication use, psychotherapy, number of outpatient treatment visits, type of health care professional, and source of payment. RESULTS: The rate of outpatient treatment for depression increased from 0.73 per 100 persons in 1987 to 2.33 in 1997 (P<.001). The proportion of treated individuals who used antidepressant medications increased from 37.3% to 74.5% (P<.001), whereas the proportion who received psychotherapy declined (71.1% vs 60.2%, P =.006). The mean number of depression treatment visits per user declined from 12.6 to 8.7 per year (P =.05). An increasingly large proportion of patients were treated by physicians for their condition (68.9% vs 87.3%, P<.001), and treatment costs were more often covered by third-party payers (39.3% to 55.2%, P<.001). CONCLUSIONS: Between 1987 and 1997, there was a marked increase in the proportion of the population who received outpatient treatment for depression. Treatment became characterized by greater involvement of physicians, greater use of psychotropic medications, and expanding availability of third-party payment, but fewer outpatient visits and less use of psychotherapy. These changes coincided with the advent of better tolerated antidepressants, increased penetration of managed care, and the development of rapid and efficient procedures for diagnosing depression in clinical practice. PMID- 11779263 TI - Sex-based analysis of outcome in patients with acute myocardial infarction treated predominantly with percutaneous coronary intervention. AB - CONTEXT: A higher mortality risk for women with acute myocardial infarction (AMI) is a common finding in studies that compare the postinfarction outcome of women vs men. It is not clear, however, whether sex is an independent predictor of death among patients systematically treated with aggressive reperfusion and medical strategies. OBJECTIVE: To assess the impact of patient's sex on outcome in a consecutive series of patients with AMI treated with a reperfusion strategy largely based on percutaneous coronary interventions. DESIGN, SETTING, AND PATIENTS: Inception cohort of 1937 patients (502 women and 1435 men) who were admitted with a diagnosis of AMI to a tertiary referral institution between January 1995 and December 2000. MAIN OUTCOME MEASURES: Mortality at 1 year after AMI. RESULTS: Compared with men, women were older (70 vs 61 years; P<.001) and had known diabetes or hypertension more often. Both men and women received essentially identical therapy with the majority of patients (86%) receiving reperfusion therapy via percutaneous coronary interventions. There were no significant differences in 1-year Kaplan-Meier death rates with 13.8% (68 cases) among women and 12.9% (184 cases) among men (unadjusted hazard ratio, 1.06; 95% confidence interval, 0.80-1.39; P =.70). After age adjustment, women had a lower risk of death (hazard ratio, 0.65; 95% confidence interval, 0.49-0.87; P =.004). CONCLUSION: Despite their more advanced age and greater prevalence of diabetes or hypertension, women with AMI who were treated with a reperfusion strategy largely based on percutaneous coronary interventions show a similar outcome as men. PMID- 11779264 TI - Serum estradiol level and risk of breast cancer during treatment with raloxifene. AB - CONTEXT: As endogenous estradiol increases, risk of breast cancer increases. Raloxifene competes with endogenous estrogen for binding to estrogen receptors in breast tissue. A woman's estradiol level may alter the effects of raloxifene on breast cancer and other outcomes. OBJECTIVE: To test the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels. DESIGN: Analysis of the Multiple Outcomes of Raloxifene Evaluation, a randomized, double-blind, placebo-controlled trial conducted from 1994 to 1999. SETTING: One hundred eighty community settings and medical practices in 25 countries including the United States. PARTICIPANTS: A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured by a central laboratory using a sensitive assay. Women with a history of breast cancer or estrogen use were excluded. INTERVENTION: Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years. MAIN OUTCOME MEASURE: New cases of histopathologically confirmed breast cancer in the treatment and placebo groups, stratified by estradiol levels. RESULTS: In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer (3.0% per 4 years; 95% confidence interval [CI], 1.8%-4.1%) than that of women with undetectable estradiol levels (0.6% per 4 years; 95% CI, 0% 1.1%; P =.005 for trend). Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% (95% CI, 53%-88%) lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group (absolute rate reduction, 2.2% [95% CI, 1.0%-3.5%; number needed to treat = 45]). In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with raloxifene (risk difference, -0.1%; 95% CI, -0.8% to 0.6%; P =.02 for the interaction). In this cohort, treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases. CONCLUSIONS: Measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women. PMID- 11779265 TI - Prevalence of Kaposi sarcoma-associated herpesvirus infection in homosexual men at beginning of and during the HIV epidemic. AB - CONTEXT: Some studies have inferred that an epidemic of Kaposi sarcoma-associated herpesvirus (KSHV) infection in homosexual men in the United States occurred concurrently with that of human immunodeficiency virus (HIV), but there have been no direct measurements of KSHV prevalence at the beginning of the HIV epidemic. OBJECTIVES: To determine the prevalence of KSHV infection in homosexual men in San Francisco, Calif, at the beginning of the HIV epidemic in 1978 and 1979 and to examine changes in prevalence of KSHV at time points from 1978 through 1996 in light of changes in sexual behavior. DESIGN, SETTING, AND PARTICIPANTS: Analysis of a clinic-based sample (n = 398) derived from the San Francisco City Clinic Cohort (ages 18-66 years) (n = 2666 for analyses herein) and from population based samples from the San Francisco Men's Health Study (MHS) (ages 25-54 years) (n = 825 and 252) and the San Francisco Young Men's Health Study (YMHS) (ages 18 29 years) (n = 428-976, and 557); behavioral studies were longitudinal and KSHV prevalence studies were cross-sectional. MAIN OUTCOME MEASURES: Antibodies against KSHV and HIV; sexual behaviors. RESULTS: The prevalence of KSHV infection in 1978 and 1979 was 26.5% of 235 (a random sample) overall (weighted for HIV infection) vs 6.9% (128/1842) for HIV in the San Francisco City Clinic Cohort sample. The prevalence of KSHV infection remained essentially unchanged between an MHS sample of 252 in 1984 and 1985 (29.6%) and a YMHS sample of 557 in 1995 and 1996 (26.4%), while HIV prevalence dropped from 49.5% of 825 in 1984 and 1985 (MHS) to 17.6% of 428 in 1992 and 1993 (YMHS). The proportion of men practicing unprotected receptive anal intercourse with 1 or more partners declined from 54% to 11% during the 1984 through 1993 period (MHS) with similar though slightly higher values in the YMHS in 1992 and 1993; whereas for unprotected oral intercourse it ranged between 60% and 90% in the 1984 through 1996 period (MHS and YMHS). CONCLUSIONS: Infection with KSHV was already highly prevalent in homosexual men when the HIV epidemic began in San Francisco, and its prevalence has been maintained at a nearly constant level. Any declines in the incidence of Kaposi sarcoma do not appear to be caused by a decline in KSHV transmission. PMID- 11779266 TI - Defining and assessing professional competence. AB - CONTEXT: Current assessment formats for physicians and trainees reliably test core knowledge and basic skills. However, they may underemphasize some important domains of professional medical practice, including interpersonal skills, lifelong learning, professionalism, and integration of core knowledge into clinical practice. OBJECTIVES: To propose a definition of professional competence, to review current means for assessing it, and to suggest new approaches to assessment. DATA SOURCES: We searched the MEDLINE database from 1966 to 2001 and reference lists of relevant articles for English-language studies of reliability or validity of measures of competence of physicians, medical students, and residents. STUDY SELECTION: We excluded articles of a purely descriptive nature, duplicate reports, reviews, and opinions and position statements, which yielded 195 relevant citations. DATA EXTRACTION: Data were abstracted by 1 of us (R.M.E.). Quality criteria for inclusion were broad, given the heterogeneity of interventions, complexity of outcome measures, and paucity of randomized or longitudinal study designs. DATA SYNTHESIS: We generated an inclusive definition of competence: the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, values, and reflection in daily practice for the benefit of the individual and the community being served. Aside from protecting the public and limiting access to advanced training, assessments should foster habits of learning and self reflection and drive institutional change. Subjective, multiple-choice, and standardized patient assessments, although reliable, underemphasize important domains of professional competence: integration of knowledge and skills, context of care, information management, teamwork, health systems, and patient-physician relationships. Few assessments observe trainees in real-life situations, incorporate the perspectives of peers and patients, or use measures that predict clinical outcomes. CONCLUSIONS: In addition to assessments of basic skills, new formats that assess clinical reasoning, expert judgment, management of ambiguity, professionalism, time management, learning strategies, and teamwork promise a multidimensional assessment while maintaining adequate reliability and validity. Institutional support, reflection, and mentoring must accompany the development of assessment programs. PMID- 11779267 TI - Corticosteroid supplementation for adrenal insufficiency. PMID- 11779268 TI - Differential influence of maternal smoking on infant birth weight: gene environment interaction and targeted intervention. PMID- 11779269 TI - Competence is a habit. PMID- 11779276 TI - Head injury in early adulthood and the lifetime risk of depression. AB - BACKGROUND: Depressive symptoms are common and can be debilitating in the months after head injury. Head injury can also have long-term cognitive effects, but little is known about the long-term risk of depression associated with head injury. We investigated the lifetime rates of depressive illness 50 years after closed head injury. METHODS: Participants were male World War II veterans who served during 1944-1945 and were hospitalized at that time for a head injury, pneumonia, or laceration, puncture, or incision wounds. We used military medical records to establish the presence and severity of closed head injuries. Veterans with (n = 520) and without (n = 1198) head injuries were interviewed in 1996-1997 for their lifetime history of depressive illness. Men with dementia were excluded. RESULTS: Veterans with head injury were more likely to report major depression in subsequent years and were more often currently depressed. Using logistic regression and controlling for age and education, the lifetime prevalence of major depression in the head injured group was 18.5% vs 13.4% in those with no head injury (odds ratio = 1.54, 95% confidence interval = 1.17 2.04). Current major depression was detected in 11.2% of the veterans with head injuries vs 8.5% of those without head injury (odds ratio = 1.63, 95% confidence interval = 1.07-2.50). This increase in depression could not be explained by a history of myocardial infarction, a history of cerebrovascular accident, or history of alcohol abuse. The lifetime risk of depression increased with severity of the head injury. CONCLUSION: The risk of depression remains elevated for decades following head injury and seems to be highest in those who have had a severe head injury. PMID- 11779277 TI - Longitudinal course of mood disorders following traumatic brain injury. PMID- 11779278 TI - Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia. AB - BACKGROUND: The clinical efficacy of dopamine D2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D2 receptors of patients with schizophrenia. METHODS: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Region-of-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D2 receptor binding. RESULTS: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. CONCLUSIONS: The lower BP values indicate fewer D2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. PMID- 11779279 TI - In vivo imaging of D2 dopamine receptors in schizophrenia: the ups and downs of neuroimaging research. PMID- 11779280 TI - Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. AB - BACKGROUND: Cortical gray matter reductions and cerebrospinal fluid (CSF) increases are robust correlates of schizophrenia, but their relationships to obstetric and other etiologic risk factors remain to be established. METHODS: Structured diagnostic interviews, obstetric hospital records, and magnetic resonance imaging scans of the brain were obtained for 64 schizophrenic or schizoaffective patients (representative of all such probands in a Helsinki, Finland, birth cohort), along with 51 of their nonpsychotic full siblings and 54 demographically similar controls without family histories of psychosis. RESULTS: Fetal hypoxia predicted reduced gray matter and increased CSF bilaterally throughout the cortex in patients (gray matter effect sizes, -0.31 to -0.56; CSF effect sizes, 0.25 to 0.47) and siblings (gray matter effect sizes, 0.33 to 0.47; CSF effect sizes, 0.17 to 0.33), most strongly in the temporal lobe. Effect sizes were 2 to 3 times greater among cases born small for their gestational age. Hypoxia also correlated significantly with ventricular enlargement, but only among patients (effect size, 0.31). In contrast, fetal hypoxia was not related to white matter among patients and siblings, nor to any tissue type in any region among controls. The associations were independent of family membership, overall brain volume, age, sex, substance abuse, and prenatal infection. CONCLUSIONS: Fetal hypoxia is associated with greater structural brain abnormalities among schizophrenic patients and their nonschizophrenic siblings than among controls at low genetic risk for schizophrenia. This pattern of results points to a gene environment interaction account of the disorder's neurodevelopmental pathogenesis. PMID- 11779281 TI - Psychiatric and substance use disorders in South Florida: racial/ethnic and gender contrasts in a young adult cohort. AB - BACKGROUND: Prevalence rates of psychiatric and substance use disorders among young adults in South Florida are presented. Unique aspects of the study include the large sample size, its ethnic diversity, and the fact that a substantial proportion of Hispanic participants were foreign born. METHODS: This study builds on a previous cohort study of students who entered middle school in 1990. A random subsample of this representative cohort (N = 1803) was interviewed between 1998 and 2000 when most were between 19 and 21 years of age. Disorders were assessed through computer-assisted personal interviews utilizing the DSM-IV version of the Michigan Composite International Diagnostic Interview. RESULTS: More than 60% of the sample met lifetime criteria for 1 or more study disorders, and 38% did so within the preceding year. Childhood conduct and major depressive and alcohol abuse disorders were the most prevalent. Although rates of affective and anxiety disorders in females were double that in males, this gender difference disappeared when attention-deficit/hyperactivity disorder, conduct disorders, and antisocial personality disorders were also considered (46.6% vs 45.7% for females vs males, respectively). Substantially lower rates were observed among African Americans for depressive disorders and substance abuse and dependence. Among Hispanics, rates tend to be lower among the foreign-born in comparison with their US-born counterparts, particularly for the substance disorders. CONCLUSIONS: The documented presence of psychiatric and substance disorders in middle and high school populations emphasizes the importance of prevention efforts in school settings. Research on the origins of ethnic and nativity differences is called for. PMID- 11779282 TI - Psychotic symptoms and paranoid ideation in a nondemented population-based sample of the very old. AB - BACKGROUND: Psychotic symptoms are reported to be uncommon in the elderly, and may be underrated in traditional epidemiological studies. METHODS: Psychotic symptoms, physical disorders, disability in daily life, and sensory impairments were assessed using results of psychiatric and physical examinations, key informant interviews, and medical record reviews in a representative sample of nondemented individuals aged 85 years living in the community or in institutions in Goteborg, Sweden (n = 347). The sample was observed for 3 years regarding psychotic symptoms, mortality, and incident dementia. RESULTS: The prevalence of any psychotic symptom was 10.1% (95% confidence interval [CI], 7.1%-13.7%); hallucinations, 6.9% (95% CI, 4.5%-10.1%); and delusions, 5.5% (95% CI, 3.3% 8.4%). The prevalence of paranoid ideation was 6.9% (95% CI, 4.5%-10.1%). Stepwise logistic regression analyses showed that hallucinations were associated with major depressive syndrome (odds ratio [OR], 3.9; 95% CI, 1.3-11.9), disability in daily life (OR, 5.2; 95% CI, 1.8-14.9), and visual deficits (OR, 3.4; 95% CI, 1.0-11.1). Delusions were associated with disability in daily life (OR, 4.9; 95% CI, 1.8-13.3). Paranoid ideation was associated with visual deficits (OR, 3.6; 95% CI, 1.2-10.5) and myocardial infarction (OR, 4.6; 95% CI, 1.7-12.6). Hallucinations (OR, 3.1; 95% CI, 1.4-6.8), delusions (OR, 2.9; 95% CI, 1.2-6.9), and paranoid ideation (OR, 2.7; 95% CI, 1.2-6.2) were each related to increased incidence of dementia from 85 to 88 years of age. Hallucinations and paranoid ideation were associated with increased 3-year mortality in women but not in men. CONCLUSIONS: We found a higher prevalence of psychotic symptoms and paranoid ideation in the elderly than previously reported, and these symptoms were associated with a poor prognosis. PMID- 11779283 TI - Paranoid psychoses in old age: much more common than previously thought? PMID- 11779284 TI - Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. AB - BACKGROUND: A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. METHODS: The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer). RESULTS: Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech. CONCLUSION: Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes. PMID- 11779285 TI - Partial validation of the atypical features subtype of major depressive disorder. AB - BACKGROUND: Symptoms of the atypical features subtype of major depressive disorder include mood reactivity, hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity. This subtype was introduced into the mood disorders section of the DSM-IV following a series of antidepressant trials showing that such patients responded preferentially to monoamine oxidase inhibitors. Studies aimed at validating the atypical features subtype have yielded inconsistent results. Our study sought to reevaluate the validity of atypical depression by examining the demographic and clinical features of a large cohort of depressed patients who met DSM-IV criteria for atypical features. METHODS: We evaluated 579 psychiatric outpatients with a current diagnosis of major depressive disorder for the presence of atypical features. Detailed demographic and clinical information was obtained for each patient through semistructured interviews. Using the available literature, we made a series of a priori hypotheses regarding how depressed patients with atypical features (n = 130) would differ from those without atypical features (n = 449). In addition, we tested the strength of the associations between each of the 5 atypical symptoms. RESULTS: Although many of the predicted hypotheses were substantiated, an equal number were not. Correlation analyses revealed modest associations between several of the atypical symptoms, but mood reactivity was not associated with any of the other symptom criteria. CONCLUSION: Our results provide partial support for the validity of the atypical features subtype of major depressive disorder. PMID- 11779286 TI - Perceived need and help-seeking in adults with mood, anxiety, or substance use disorders. AB - BACKGROUND: A majority of adults with common mental disorders do not seek professional help. To better understand why not, we examined the correlates of various stages of help-seeking, including perceived need for professional help, seeking such help, and from which professionals participants sought help. METHODS: The sample for this study comprised 1792 participants in the National Comorbidity Survey, conducted from 1990-1992, who were diagnosed with a 12-month DSM-III-R mood, anxiety, or substance disorder. In this sample, we assessed correlates of perceived need for professional help, seeking professional help among those with a need, and, among those who did seek professional help, seeking help from mental health professionals. RESULTS: Mood disorders, comorbid mood and anxiety disorders, and mental disorders associated with impairment in role functioning or suicidality were strong predictors of perceived need. Psychopathology was also associated with the decision to seek help from mental health professionals, but not with the decision to seek professional help overall. After controlling for the nature and severity of psychopathology, various sociodemographic and attitudinal factors appeared to be associated with perception of need, help-seeking, and participants' choices of professionals. CONCLUSIONS: Unmet need for mental health care is a serious public health problem. Meeting this need requires expanding our attention beyond psychopathology to various evaluations and decisions that affect help-seeking. Our results suggest the importance of attitude and behavior change strategies in reducing the gap between need and care. PMID- 11779287 TI - Hypnosis and neuroscience: a cross talk between clinical and cognitive research. AB - Despite its long use in clinical settings, the checkered reputation of hypnosis has dimmed its promise as a research instrument. Whereas cognitive neuroscience has scantily fostered hypnosis as a manipulation, neuroimaging techniques offer new opportunities to use hypnosis and posthypnotic suggestion as probes into brain mechanisms and, reciprocally, provide a means of studying hypnosis itself. We outline how the hypnotic state can serve as a way to tap neurocognitive questions and how cognitive assays can in turn shed new light on the neural bases of hypnosis. This cross talk should enhance research and clinical applications. PMID- 11779288 TI - A correction. PMID- 11779290 TI - Eicosapentaenoic acid in treatment-resistant depression. PMID- 11779291 TI - Monoclonal antibodies in the prehybridoma era: a brief historical perspective and personal reminiscence. AB - Emil von Behring, an immunologist, received the first Nobel Prize in Physiology or Medicine in 1901 for his studies on serum therapy of diphtheria. Seventeen Nobel Prizes have been awarded to scientists for their work in immunology and related disciplines. E. Metchnikoff and P. Ehrlich were pioneers who became associated with cellular and humoral theories of immunity, respectively. Almroth Wright described opsonins and was a vigorous advocate of vaccine therapy for bacterial diseases. He was an influential scientist and mentor who served as the model for Bernard Shaw's play, The Doctor's Dilemma. Immunochemistry developed through the work of K. Landsteiner, M. Heidelberger, E. Kabat, and many others. At mid-20th century, cell-selection theories of antibody formation championed by N. Jerne and F.M. Burnet shifted the field from a chemical to a biological orientation. Myeloma immunoglobulins, Bence Jones proteins, and monoclonal macroglobulins from patients and mice played a central role in elucidation of normal immunoglobulin structure, genetics, synthesis, and metabolism. By the late 1960s, antibody activity in some human myeloma and Waldenstrom macroglobulin paraproteins had been documented. Subsequently, other human paraproteins were shown to have antigen-binding properties, principally to auto- or bacterial antigens. The development of hybridoma technology by G. Kohler and C. Milstein revolutionized immunology after 1975. These investigators demonstrated that antibody-producing cells of virtually any desired specificity could be fused with a myeloma cell line, the result being unlimited amounts of homogeneous (monoclonal) antibodies carrying that specificity. Monoclonal antibodies have been shown to have efficacy in cancer therapy, particularly in patients with lymphoma and breast cancer. It is likely that this approach, alone and in combination with other modalities, will prove useful for patients with additional types of malignancies. PMID- 11779292 TI - Diffuse large-cell lymphomas: a review of therapy. AB - In this review, the historical and modern classification schemes of non-Hodgkin's lymphoma (NHL) will be briefly summarized, with a critical review of the evolution and current state of treatment strategies for diffuse large-cell lymphoma (DLCL). We provide current treatment recommendations for newly diagnosed disease and indicate the areas of active clinical investigation. In the past, many of the promising phase II studies in DLCL have appeared beneficial based on patient selection criteria and not the therapeutic result. Lessons learned in clinical trials in NHL may serve as a paradigm for other cancer investigations. PMID- 11779293 TI - Feasibility and safety of outpatient Bexxar therapy (tositumomab and iodine I 131 tositumomab) for non-Hodgkin's lymphoma based on radiation doses to family members. AB - Radioimmunotherapy with anti-CD20 antibodies is a promising treatment approach for relapsed low-grade non-Hodgkin's lymphoma. Under revised Nuclear Regulatory Commission regulations (May 1997), patients may be released following treatment provided the maximum dose to any individual is not likely to exceed 500 mrem. Non Hodgkin's lymphoma patients have been studied to evaluate radiation exposure to caregivers/family members after outpatient treatment with tositumomab and iodine I 131 tositumomab (Bexxar therapy). Estimates of total radiation doses to individuals expected to be maximally exposed to patients posttreatment have revealed that the doses should be within revised guidelines. In a University of Nebraska Medical Center study, the predicted total radiation doses (based on patient dose rate at 1 meter) ranged from 95-423 mrem. Family members were provided radiation-monitoring devices to directly monitor radiation exposure. Measured doses ranged from 10-409 mrem. In this and other studies, estimated and measured dose equivalents to maximally exposed individuals were below 500 mrem. Measured doses were, in most instances, lower than those predicted by patient specific calculations, thus confirming the validity of the calculated dose predictions. Therefore, radioimmunotherapy with tositumomab and iodine I 131 tositumomab can be safely conducted on an outpatient basis. PMID- 11779294 TI - Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. AB - To evaluate the risk of acute and late side effects in children whose mothers received chemotherapy during pregnancy for hematological malignancies, we performed an analysis of 84 children with a long-term follow-up. The 84 children in our study were born to mothers with hematological malignancies (29 acute leukemia, 26 Hodgkin's disease, and 29 malignant lymphoma) who received chemotherapy during pregnancy, including 38 during the first trimester. These children were examined for physical health; growth; development; and hematological, cytogenetic, neurological, psychological, and learning disorders. The occurrence of cancer or acute leukemia in these children was also considered. Some of these patients have become parents, and their children were also considered in this analysis. In all of the children studied, including the 12 second-generation children, the birth weight was normal; learning and educational performance were normal; and no congenital, neurological, or psychological abnormalities were observed. With a median follow-up of 18.7 years (range, 6-29 years), no cancer or acute leukemia has been observed. These results confirm our previous reports, suggesting that if a pregnant patient has an aggressive hematological malignancy, chemotherapy at full doses can be safely administered, even during the first trimester, if cure of the hematological malignancy is considered reasonable. PMID- 11779295 TI - Blastic natural killer cell leukemia/lymphoma presenting as overt leukemia. AB - Blastic natural killer (NK)-cell leukemia/lymphoma is a neoplasm of NK origin with aggressive behavior. The disease affects mainly elderly people and often presents with skin lesions and overt leukemia. Blastic morphology, an NK-cell immunophenotype, and lack of association with Epstein-Barr virus are the clues for the diagnosis. We report herein, the case of a patient with a blastic NK-cell leukemia/lymphoma with overt leukemia at diagnosis, who achieved a complete response after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. However, the patient relapsed a few months later and died due to disease progression. Cases of blastic NK-cell leukemia/ lymphoma previously reported are briefly reviewed. PMID- 11779297 TI - Durable remission in recurrent T-cell-rich B-cell lymphoma with the anti-CD20 antibody rituximab. AB - A diagnostic continuum exists between lymphocyte-predominant Hodgkin's disease, T cell-rich B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma. While TCRBCLs are uncommon, their clinical and morphologic presentation can mimic other Hodgkin's and non-Hodgkin's lymphomas from which they must be distinguished for diagnosis and treatment. We present an unusual case of a 30-year-old man with recurrent TCRBCL arising from lymphocyte-predominant Hodgkin's disease with remarkable response to treatment with the anti-CD20 antibody, rituximab. PMID- 11779298 TI - Phase II trial of Remitogen (humanized 1D10) monoclonal antibody targeting class II in patients with relapsed low-grade or follicular lymphoma. PMID- 11779299 TI - Community ear care delivery by community ear assistants and volunteers: a pilot programme. AB - Hearing impairment is a major public health problem in Nepal. The present service delivery, however, is mainly hospital based and is limited to large towns. Those people residing in rural areas lack many basic needs including ear care services. The collaborative community volunteer-based ear care pilot programme implemented in Banke, Nepal aims to reach out to those rural areas by establishing sustainable primary ear care services, empowering and utilizing local resources. The focus of the programme is to promote multi-sector improvement in sanitation, nutrition, immunization, breast-feeding and timely care and support to ear patients to help prevent hearing impairment mainly from the sequelae of otitis media. PMID- 11779300 TI - Adult-onset otitis media with effusion: results following ventilation tube insertion. AB - The outcome of otitis media with effusion (OME) in children is generally good. However, it is less clear in adults. All adult patients who had a ventilation tube inserted for OME at the Ipswich Hospital between 1996 and 1997 were studied. Of 53 patients studied, 28 had had a previous history of ventilation tube insertion. Furthermore, at 15-27 months following ventilation tube insertion, the ventilation tube had already extruded in 31 patients and the OME had already recurred in 19 of these. Endoscopic examination revealed that many patients still had evidence of inflammation at the lateral nasal wall (26.4 per cent) and at the eustachian tube orifice (51 per cent). There is also a strong history of atopy in the studied group and the skin prick test was positive in 57 per cent of the patients. This study shows that many patients with adult-onset OME have underlying pathology that could lead to recurrence of OME following ventilation tube extrusion. PMID- 11779301 TI - Outcome of 22 cases of perforated tympanic membrane caused by otomycosis. AB - Twenty-two cases of perforated tympanic membrane due to fungal otitis externa were observed over a five-year period. The diagnosis of fungal otitis externa was made on clinical grounds due to the obvious presence of fungal bloom in the external ear canal. Some perforations were noted at the first treatment after the fungal debris had been removed from the external ear canal using a microscope. Other perforations were observed to develop over a few days. Initially, a discrete area of the tympanic membrane appeared white and opaque. As time progressed the white area disintegrated, forming a perforation. Once the otitis externa had resolved most perforations healed spontaneously. Two that were observed to develop during treatment required a myringoplasty. Another one closed significantly but a tiny persistent perforation required cauterization with trichloracetic acid to encourage it to close over completely. The only residual hearing loss was in a case with almost total disintegration of the tympanic membrane requiring a myringoplasty. Treatment of fungal otitis externa for the patients in this series was aural toilet using suction under a microscope and insertion of a gauze wick saturated in a combination of hydrocortisone, clotrimazole, framycetin and gramicidin. PMID- 11779302 TI - Expression of telomerase activity in cholesteatoma otitis media. AB - Telomerase maintains the length of telomeres in immortal cells and is also often associated with cell proliferation. Cholesteatoma epithelium is characterized by a dysregulation with hyperproliferative growth. The study evaluated the telomerase activity in cholesteatoma and normal retro-auricular skin to discover the relationship between telomerase expression and clinical findings. Twenty-two samples of cholesteatoma and 15 samples of retro-auricular skin were obtained from patients undergoing middle-ear surgery. The telomerase activity was detected by the telomerase repeat amplification protocol (TRAP) assay method. Seventeen of the 22 (77.3 per cent) cholesteatoma cases expressed telomerase activity, whereas none of the 15 retro-auricular normal skin (0 per cent) detected telomerase activity. There was no significant difference between telomerase expressions and clinical findings, including hearing level, duration of disease, and the degree of extension (p>0.05). The high expression of telomerase in cholesteatoma suggests that the activation of telomerase may be related to the proliferative nature of cholesteatoma. PMID- 11779303 TI - Use of the auricular composite graft in nasal reconstruction. AB - We present our experience using conchal composite grafts in major and minor nasal reconstruction. We believe that composite grafts have an important and under utilized role as an adjunct to the paramedian forehead flap on total and subtotal nasal reconstruction, as well as in providing an internal lining and support in stenosis of the nasal vestibule. The use of a composite conchal graft as an inner lining and support is often preferential to a septal composite or hinge flap that often results in a septal perforation with its associated morbidity. We recognize that a composite conchal graft used for reconstruction of the alar margin provides a suboptimal result after several months. This is because it is not always possible to replace a whole aesthetic subunit and whilst the site the graft is harvested from often allows the correct contour to be chosen, the quality of skin is often different and this can be seen after several weeks when any post-operative oedema has settled. PMID- 11779304 TI - Per oral awake flexible fibre-optic laryngoscopy in the investigation of children with stridor without respiratory distress. AB - Use of rigid direct larygnoscopy (RDL) in the investigation of stridor in children is well recognized. This study presents awake flexible fibre-optic laryngoscopy (FFL) as the first line in investigation of children, under six months of age, who present with stridor without any associated respiratory distress. Using the per oral approach the procedures were conducted either in the out-patient department or in the ward. No anaesthesia, local or general, nor sedation was used. Of the 20 cases included in the study, in 16 (80 per cent) cases a working diagnosis was reached on awake FFL. Eleven had laryngomalacia, two subglottic stenosis, one glottic web and two were normal. Only four (20 per cent) cases needed RDL to reach a definitive diagnosis. There were no problems with the maintenance of the airway during the procedure. It is particularly useful in the diagnosis of functional abnormalities of the larynx, such as laryngomalacia and vocal fold palsies. Awake FFL using the per oral approach is a safe and reliable technique for reaching a working diagnosis in approximately 80 per cent of cases. PMID- 11779305 TI - Long-term results of laser-assisted uvulopalatoplasty for snoring. AB - We present the ongoing results of the series of 53 consecutive patients who underwent laser-assisted uvulopalatoplasty (LAUP) for snoring at the Kent and Canterbury Hospital. Twenty-nine patients (55 per cent) were completely satisfied with their surgery 18 to 24 months following LAUP when previously questioned via telephone questionnaire. We have followed up the 29 patients with a previously successful result at between 70 and 79 months following surgery. They underwent an average of 1.6 procedures. Twelve patients (22 per cent) continue to be completely satisfied at this late stage, and a further 12 (22 per cent) have some ongoing improvement in their snoring. Only three patients have indicated that a previously successful result has failed since the previous survey. The failure rate of LAUP in the treatment of snoring is seen predominantly in the first two years following surgery, but some long-term subjective recurrence of snoring does occur. PMID- 11779306 TI - A novel approach to the removal of superglue from the ear. AB - The ability of superglue (a cyanoacrylate adhesive) to bond strongly and quickly to skin presents considerable problems when it is inserted into the ear. A case of a patient who inadvertently self-administered Bostik superglue into her left external auditory meatus is reported. The superglue was removed successfully, in the form of a cast, with warm three per cent hydrogen peroxide without damaging the meatus or the typanic membrane. The use of hydrogen peroxide to remove superglue from the ear has not been described previously. PMID- 11779307 TI - Osseo-integration in Paget's disease: the bone-anchored hearing aid in the rehabilitation of Pagetic deafness. AB - The first report of a patient with gross Paget's disease and progressive hearing loss who successfully underwent hearing rehabilitation with an osseo-integrated hearing aid is presented. The otological manifestations of Paget's disease and the principles of osseo-integration are discussed. The use of a bone-anchored hearing aid (BAHA) in selected patients with Paget's disease can provide useful amplification and hearing rehabilitation. PMID- 11779308 TI - Sudden onset bilateral sensorineural hearing loss: a manifestation of occult breast carcinoma. AB - Diffuse infiltration of the meninges by metastatic carcinoma (meningeal carcinomastosis) is a potential complication of systemic malignancy. It may present with a variety of neurological symptoms as any aspect of the neuraxis can be affected. Often there is a history of pre-existing malignancy. The authors describe a case with an initial presentation of sudden onset profound bilateral sensorineural hearing loss. The underlying pathology was found to be an occult breast carcinoma, a previously unreported finding. The role of cerebrospinal fluid cytology and radio-imaging in diagnosis is discussed. All previously reported cases of sudden hearing loss and meningeal carcinomatosis are reviewed. PMID- 11779310 TI - Peri-orbital surgical emphysema following functional endoscopic sinus surgery, during extubation. AB - We present a case of peri-orbital surgical emphysema following functional endoscopic sinus surgery (FESS), due to extubation with simultaneous manual inhalation with a closed expiratory valve. This complication has not been previously reported in association with general anaesthetic and FESS. Patients undergoing FESS are advised against nose blowing. However, we recommend that the anaesthetist working with a surgeon who performs FESS should also be warned not to use manual inhalation with a closed expiratory valve while extubating, as this can cause peri-orbital surgical emphysema. PMID- 11779309 TI - A case of sensorineural deafness following ingestion of Ecstasy. AB - Ecstasy is a substance of abuse commonly associated with the dance scene and taken by many young people. A brief history of Ecstasy and its side-effects is given. A case of ototoxicity is presented, as an additional side-effect to the long list of complications caused by Ecstasy. PMID- 11779311 TI - Tardive dystonia of the larynx in a quadriplegic patient: an unusual cause of stridor. AB - We describe a case of a quadriplegic brain-damaged man with severe upper airway obstruction. A diagnosis of tardive dystonia affecting the vocal folds was made and confirmed by flexible nasopharyngoscopy. Emergency tracheotomy was required. The tardive movement disorder resolved with discontinuation of thioridazine. This case serves to heighten awareness of potentially serious airway complications associated with the use of anti-psychotics and anti-emetics particularly in those with organic brain disease. PMID- 11779312 TI - A hoarse voice: atypical mycobacterial infection of the larynx. AB - Myobacterium malmoense is a non-tuberculous mycobacterium that most commonly causes pulmonary infection, particularly in patients with underlying pulmonary disease or immunodeficiency. We describe a case of Mycobacterium malmoense infection of the larynx in a previously well middle-aged woman, which has previously not been reported. The case highlights the importance of considering atypical mycobacterial infection in the differential diagnosis of laryngeal lesions. PMID- 11779313 TI - Oro-facial granulomatosis: a laryngeal presentation. AB - We report the first case of oro-facial granulomatosis (OFG) presenting in pregnancy with laryngeal manifestations. PMID- 11779315 TI - Plasma cell infiltration of the upper aerodigestive tract treated with radiation therapy. AB - A case of chronic, fluctuating plasma cell gingivostomatitis that progressed despite chemotherapy and surgery is reported. This is the first case reported of treatment with radiation therapy, and one of the few cases reported where the infiltrate has reached the larynx. After receiving low dose radiation therapy, via a conformal technique encompassing the respiratory mucosal lining from the base of tongue to carina, there has been symptomatic improvement. PMID- 11779314 TI - Metastatic malignant melanoma of the larynx. AB - Metastatic malignant melanoma of the larynx is considered to be extremely rare by most authors. This paper describes a 78-year-old patient, previously treated for cutaneous malignant melanoma and intestinal fibrosarcoma, who presented with stridor due to a metastatic melanoma in the larynx. It was a pedunculated lesion and surgical excision of the lesion was accomplished with a tonsillar snare. This paper further discusses the evolving history, diagnosis and treatment of this metastatic tumour, and reviews the literature regarding previously reported cases. PMID- 11779316 TI - Primary malignant melanoma of the pharynx. AB - Primary mucosal malignant melanomas are rare. They appear late in life and their prognosis is grave. Although there is no consensus on therapy, wide surgical resection followed by radiotherapy, chemotherapy and immunotherapy are treatment modalities. In this report we present a case of widespread primary mucosal malignant melanoma located in the pharynx. After immunotherapy (four cycles of interleukin-2 and interferon-alpha) and chemotherapy (four cycles of cisplatin and dacarbazine) has been applied as primary therapy for suppression of the mass, transoral total pharyngeal resection was performed. After surgery three cycles of immunotherapy and three cycles of chemotherapy were administered followed by radiotherapy (total dose of 6600 cGy). An additional three cycles of immunotherapy and chemotherapy were administered. Although no local recurrence was observed during the 14 months of follow-up after the completion of radiotherapy, cranial and lung metastasis were detected in the 12th month. PMID- 11779317 TI - Palliative tracheal stenting in invasive papillary thyroid carcinoma. AB - Malignant tracheal stenosis presents a considerable challenge to the head and neck surgeon. The use of intraluminal stents has been previously described, but current literature notes a paucity of supportive physiological data. We describe the use of a self-expanding metallic Wallstent in the palliation of a case of papillary thyroid carcinoma. This is accompanied by significant improvement in quantitative pulmonary function. PMID- 11779318 TI - Nitinol stent insertion for post-pneumonectomy syndrome. AB - Post-pneumonectomy syndrome is an unusual condition, that can occur a variable period of time after a patient has had a pneumonectomy. Management of this syndrome has been described using a number of different techniques, often with considerable mortality. We present a case report where this condition was treated successfully by insertion of an expandable Nitinol stent. This is the first time this technique has been described to treat this condition, and we feel it may be the procedure of choice in managing these patients. PMID- 11779319 TI - Solitary fibrous tumour of the thyroid gland. AB - Solitary fibrous tumours of the thyroid gland are rare; only five cases have been reported in the literature. Clinically, they present as a long-standing firm mass in the thyroid. Histologically, they show a range of appearances including so called 'patternless growth pattern', spindle-cell morphology, alternating hypo- and hyper-cellular areas, keloid-like hyalinization and a prominent haemangiopericytoma - like architecture. The behaviour of extrathoracic solitary fibrous tumours is unpredictable and requires careful, long-term follow-up. PMID- 11779320 TI - The JLO Travelling Fellowship Report 2001. Visit to Professor Anders Tjellstrom, Sahlgren's University Hospital, Gothenburg, Sweden, and Professor CWRT Cremers, University Hospital, Nijmegen, The Netherlands. PMID- 11779321 TI - Necropsy in head and neck cancer patient. PMID- 11779322 TI - Management of ingested foreign bodies: a retrospective review of 5240 patients. AB - This review was carried out to assess the effectiveness of our protocol designed for the management of ingested foreign bodies. It was a retrospective review of 5240 patients with ingested foreign bodies admitted over a five-year period to the Ear Nose and Throat Unit. These patients were managed according to a standardized protocol which was adopted and modified from our previous study. Under his management protocol, the mean hospital stay was 1.6 days. Flexible oesophagoscopy under local anaesthesia, and rigid oesophagoscopy under general anaesthesia, were performed in 1.5 per cent and 7.7 per cent of cases respectively. Major complications including oesophageal perforation and deep neck abscesses occurred in 0.19 per cent of patients. There was no mortality. This management protocol for ingested foreign bodies was both safe and cost-effective when compared to similar studies reported in the literature. PMID- 11779323 TI - The use of middle ear endoscopy: has residual cholesteatoma been eliminated? AB - Oto-endoscopes allow surgeons to control blind pockets within the middle ear. Many surgeons credit the reduction of residual cholesteatoma in their practice to the use of oto-endoscopes. Since 1988, the author has been using rigid endoscopes in combination with the operating microscope in cholesteatoma surgery. Between 1988 and 1999, 231 primary cholesteatoma operations were performed. The operations included closed cavity mastoidectomy (53 patients), small cavity mastoidectomy (115 patients), open mastoidectomy with primary canal wall reconstruction (44 patients) or mastoid obliteration (19 patients). The median follow-up period was 6.5 years. The incidence of residual cholesteatoma is closed cavity mastoidectomy (9.4 per cent) was found to be similar to that of open cavity mastoidectomy (8.7 per cent). Site analysis of the residual cholesteatoma revealed an incidence of 3.6 per cent in the epitympanum, 10.5 per cent in the sinus tympani and 0.7 per cent in the mastoid bowl. This study showed that residual cholesteatoma has not been eliminated with the use of middle-ear endoscopy, although the incidence has reduced the figures for closed cavity mastoidectomy to single figures. PMID- 11779324 TI - Clinical features of newly presenting cases of chronic otitis media. AB - The clinical features of 58 consecutive patients presenting with a new case of chronic otitis media were prospectively collected over a 15-month period. Twenty three ears had a keratin filled marginal or attic defect (14 with cholesteatoma), 20 had a self-clearing marginal or attic defect, and 21 had a central tympanic membrane perforation (including one cholesteatoma). Twenty patients (35 per cent) had an abnormal finding in the opposite ear. The patients' ages were dispersed over a wide range of age groups with a mean age of 34 years. Hearing loss was the most common presenting symptom (78 per cent), followed by otorrhoea (64 per cent). A significant proportion of patients denied any history of otorrhoea. Our findings should alert the clinician to suspecting a new case of COM in patients with hearing loss of any age, with, or without, a history of otorrhoea, regardless of their background ear history or the duration of their symptoms. PMID- 11779325 TI - Role of mastoid obliteration in patients with persistent cavity problems following modified radical mastoidectomy. AB - A randomized clinical trial was conducted to determine the efficacy of mastoid obliteration in controlling persistent ear discharge, wax accumulation, fungal infection and granulation tissue formation in patients with cavity problems following modified radical mastoidectomy (MRM). Thirty patients underwent revision mastoidectomy with mastoid obliteration using a temporoparietal fascial flap. They were then followed up over a one-year period and the stated parameters observed. They were compared with 30 patients with similar complaints who were treated conservatively and kept under observation for 12 months. On follow-up, the number of patients in both the groups suffering from various cavity problems was compared. The chi-squared test was applied to the results and it was determined that there was a significantly lower incidence of discharging ear and formation of granulations in the operative group. However, audiological status, development of otomycosis and wax accumulation did not reveal any significant variation between the two groups. PMID- 11779326 TI - The management of severe infectious mononucleosis tonsillitis and upper airway obstruction. AB - Acute tonsillectomy has been advocated for severe infectious mononucleosis (IM) pharyngotonsillitis with upper airway obstruction (UAO) and not responding to corticosteroids. This paper reviews and rationalizes our management. A five-year chart review was carried out with a follow-up telephone survey. There were 36 admissions. Nine had UAO of whom 89 per cent (eight of nine patients) had a tonsillectomy. The diagnosis of UAO was not standardized. Twenty-seven patients did not have UAO and only a small proportion of these patients, 16 per cent (four of 25) went on to have an elective tonsillectomy. Corticosteroids made no significant difference to the tonsillectomy rate. UAO appears to identify patients with more severe disease who are likely to suffer recurrent tonsillitis. Acute tonsillectomy is an appropriate treatment option for this subgroup. The diagnosis of significant IM UAO is not defined and a schema is proposed. Recurrent tonsillitis is an uncommon sequela of severe IM pharyngotonsillitis without UAO. PMID- 11779327 TI - A rapid access husky voice clinic: useful in diagnosing laryngeal pathology. AB - A new established pilot husky voice clinic with agreed referral protocols for patients at risk of developing laryngeal malignancy was audited. Thirty-four patients were seen, 41.2 per cent having abnormal findings on flexible nasendoscopy, 29.4 per cent requiring rigid endoscopy, 38.1 per cent were discharged after the initial visit. One case of early laryngeal cancer was picked up during this period from this group of patients. The data for the remaining population in Portsmouth was examined, and a further eight cases of laryngeal cancer were diagnosed in keeping with national incidences. A rapid access clinic with agreed protocols that referring practitioners adhered to, was useful for diagnosing laryngeal cancer and should meet the requirements of the government's 14-day rule. PMID- 11779328 TI - Long-term oncological results in 47 cases of jugular paraganglioma surgery with special emphasis on the facial nerve issue. AB - Oncological and functional results were assessed in 47 type C and/or D jugular paraganglioma operated on between 1984 and 1998 using the classical infratemporal fossa type A approach (mean follow-up = 66 months). In 24 instances, however, the facial nerve was not re-routed. Total resection was achieved in 33 cases (70 per cent). In 25 patients available for follow-up this resulted in a 92 per cent cure rate while two patients (eight per cent) developed recurrences that are being followed-up clinically and radiologically. Sub-total resection, leaving infracentimetric tumour remnants after being coagulated, was achieved in 14 cases (30 per cent). In 11 patients available for follow-up, only three cases developed tumour regrowth (27 per cent) that was controlled by salvage irradiation or surgery while in the other cases tumour remnants remained stable (73 per cent). Symptomatic post-operative lower cranial nerve impairment was observed in 23 per cent. When results were analysed depending on whether the facial nerve had been re-routed (n = 18) or not (n = 24), the incidence of facial paralysis HB grade III or more at one year was 33 per cent and eight per cent, respectively. Total resection was achieved in 56 per cent when the facial nerve was re-routed versus 75 per cent when it was not, the difference being due to a higher incidence of large tumours in the first group. The present study suggests that: 1) surgical resection of jugular paraganglioma provides overall satisfactory results, i.e. a 86 per cent rate of either cure or tumour remnant stabilization, but carries a significant risk of iatrogeny; 2) complete tumour removal should not be attempted, especially in patients over 60 years of age with no pre-operative neurological deficits, since leaving infracentimetric tumour remnants has no major detrimental effect on the final outcome; 3) facial nerve transposition carries a significant risk of cosmetic sequelae while it does not provide significant advantages in terms of tumour resection and long-term oncological control. PMID- 11779329 TI - Secondary primary malignancies in head and neck squamous cell carcinoma. AB - Second primary malignancies pose a significant clinical challenge to the head and neck oncologist. The prognosis for these patients is poor and therefore early detection of these tumours is essential. There are considerable differences in the reported cohorts of patients and the biological behaviour of these tumours throughout the world literature. This is particularly marked when there is considerable demographic variation present. The behaviour of second primary malignancies in 425 Irish patients with head and neck cancer was reviewed retrospectively. The overall incidence of second cancers was 8.5 per cent. There were a higher proportion of oral cancer patients 47 per cent, the second cancers overall presented with a more advanced T stage, and the overall five-year survival was much lower than that of the index tumour. PMID- 11779330 TI - The otologic T-tube: a cost effective dacryocystorhinostomy stent. AB - Endoscopic endonasal dacryocystorhinostomy (EDCR) has established itself as a popular means of relieving post-saccal obstruction of the naso-lacrimal ducts. Soft tissue stenosis of the rhinostomy is a significant cause of long-term failure. We describe the technique of using a standard otological T-tube as a cheap and easy self-retaining stent to ensure a patent rhinostomy following EDCR. PMID- 11779331 TI - Enlarged approach to the anterior cervical spine. AB - In this report a new enlarged approach to the anterior cervical spine is presented. A 66-year-old female, having a large C3-C4-C5 chordoma, recurrent after surgery and following radiotherapy, underwent a surgical resection. The approach allows a wide retraction of the nasopharynx, oropharynx and larynx from the midline, only sacrificing the superior laryngeal nerve on one side. Its continuity can be re-established later by adopting the stent in tube technique. The approach we used presents all the risks of infection common in trans-oral approaches. For this reason, closure of the pharynx in two layers must be meticulous and watertight and reinforced by using a myofascial sternocleidomastoid flap, according to the tracheoesophageal fistula closure technique. A correct alignment of the tongue, the pre-plating of the mandible and the correct suture of the vermillion border guarantee excellent cosmetic and functional results. PMID- 11779332 TI - In-the-ear hearing aids within auricular prostheses. AB - We report a child with bilateral congenital microtia in whom cosmetic and auditory rehabilitation has been effected using in-the-ear hearing aids within prostheses overlying the rudimentary external auditory meati after canaloplasty. This novel method of auditory rehabilitation has not been reported before and is suitable in selected cases. The prostheses themselves were successfully secured using a prosthetic contact adhesive we have developed that offers excellent retention, little if any skin reaction, and high patient acceptability. PMID- 11779333 TI - Periodic alternating nystagmus associated with Arnold-Chiari malformation. AB - The Arnold-Chiari malformation type I is a rare congenital condition characterized by herniation of the cerebellar tonsils into the upper cervical spinal tract. Various otoneurological manifestations occur in patients with the disease, which has usually been associated with a downbeat type of nystagmus. In this paper a case with this condition is reported presenting with periodic alternating nystagmus (PAN), which is a rare type of nystagmus observed in diseases of the central nervous system of different pathologies. The patient had a complete otoneurological examination and vestibular function testing. Diagnosis was established by using magnetic resonance imaging (MRI). PMID- 11779334 TI - Large cholesterol granuloma of the petrous apex treated via subcochlear drainage. AB - This is a case report of a patient with bilateral cholesterol granuloma of the petrous apex, who presented with unilateral symptoms. Initially suspected as having a dermoid cyst, he underwent posterior fossa exploration, drainage and biopsy. Symptoms recurred one year later and subcochlear drainage of the petrous apex cyst was successfully performed. Follow-up for over 18 months shows no clinical nor imaging signs of recurrence. A MEDLINE literature search was carried out and relevant paper publications reviewed. Case presentation including initial, pre- and post-operative imaging is presented. This is followed by discussion of current concepts on the presentation and management of large cholesterol cysts of the petrous apex. PMID- 11779335 TI - Sebaceous carcinoma of the nasal vestibule. AB - Sebaceous carcinoma is a rare disease arising from holocrine adnexal components of the skin. Fewer than 400 cases have been reported worldwide and only about 19 are from the nose. We present a sebaceous cancer of the nasal vestibule in a patient who, with adequate excision, is disease-free after two years. PMID- 11779336 TI - Solitary neurofibroma of the nasal cavity: resection with endoscopic surgery. AB - We present a case of neurofibroma of the nasal cavity treated by endoscopic surgery. A 71-year-old female had complained of left-sided nasal obstruction for the past four years. Anterior rhinoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a tumour involving the left nasal cavity. Histological and immunohistochemical examination showed the tumour to be a neurofibroma. The tumour was resected with endoscopic surgery. Neurofibroma arising in the area of the nose and paranasal sinuses is rare. We discuss the clinical and pathological characters of neurofibroma arising in the nasal cavity. PMID- 11779337 TI - Endoscopic laser dacryocystorhinostomy. An unusual post-operative finding: re opening of the nasolacrimal duct. AB - Endoscopic laser dacryocystorhinostomy (DCR) is a recognized technique for the surgical treatment of epiphora. Nasolacrimal duct obstruction is surgically bypassed by creating a passage from the lacrimal sac to the nasal cavity (rhinostomy). Some patients have undergone endonasal laser-assisted DCR, and were found to have an obstructed rhinostomy at follow-up. However, they reported a subjective improvement in their symptoms. Five such patients, at six months follow-up, were found to have a non-functioning rhinostomy with fluorescein dye emerging from under the inferior turbinate. These five patients along with four controls had post-operative macrodacryocystograms (MDCG) to delineate the anatomical passage by which tears were entering the nasal cavity. In the control group, clear passage of contrast into the middle meatus was demonstrated in three of the four subjects. In the study group, passage of dye to the inferior meatus, via the nasolacrimal duct was demonstrated in four of the five subjects. It is well recognized that a proportion of patients suffering from epiphora will have a natural resolution of their symptoms. Our results demonstrate that the resolution of epiphora in some operated patients was due to a re-opening of the nasolacrimal duct, and not because of a patent rhinostomy. PMID- 11779338 TI - Alveolar rhabdomyosarcoma presenting as a peritonsillar abscess. AB - A rhabdomyosarcoma of the head and neck region is a rare childhood neoplasm often presenting with vague symptoms that can easily mimic other diseases. We present an unusual case of an alveolar rhabdomyosarcoma of the soft palate in a three year-old child, that presented as a peritonsillar abscess. PMID- 11779339 TI - Kearns-Sayre syndrome: presenting with vocal fold palsy. AB - We present the first documented case of Kearns-Sayre syndrome presenting with a vocal fold palsy. PMID- 11779340 TI - Extramedullary plasmacytoma of the submandibular gland. AB - Extramedullary plasmacytoma in the submandibular region is rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiological and pathological studies including immunohistochemistry. We report a case of extramedullary plasmacytoma in the submandibular gland. A review of the literature suggests that it has a good prognosis, if multiple myeloma is excluded. This patient was treated by surgical excision followed by radiotherapy. PMID- 11779341 TI - Pilomatrixoma in the parotid region. AB - Pilomatrixoma is a benign neoplasm of the hair follicle that may present to the otolaryngologist as a palpable swelling in the head and neck area. The correct diagnosis may be difficult to confirm when it presents in the region of the parotid. The use of fine needle aspiration cytology (FNAC) and diagnostic imaging may help confirm the diagnosis. The correct treatment is surgical. However, should the tumour recur then the possibility of malignancy should be considered. PMID- 11779342 TI - Fourth branchial arch fistula and suppurative thyroiditis: a life-threatening infection. AB - A potentially life-threatening case of recurrent left-sided thyroid abscess formation secondary to a fourth branchial arch sinus fistula is presented. The patient developed a reversible left vocal fold palsy during an acute episode of suppurative thyroiditis requiring a temporary tracheostomy due to a compromised airway. Investigations commonly used to demonstrate this anomaly may fail to confirm the diagnosis as in the case presented and exploratory surgery with excision of the fistulous tract should still be considered. We describe a method of repairing the pharyngeal opening to reduce the risk of recurrence or pharyngeal leak. PMID- 11779343 TI - T/NK cell non-Hodgkin's lymphoma of the sinonasal tract. AB - Non-Hodgkin's lymphoma of the sinonasal tract is now recognized as an important cause of destructive midfacial lesions formally designated as idiopathic inflammatory processes, and commonly treated with local radiotherapy in a bid to halt the destructive process. However, left untreated, the natural history of this disease remains largely unknown. We report a case which demonstrates the slow and apparently indolent natural course that these lymphomas, if left untreated, may display, before finally evolving into overwhelming and fatal disease. We also take the opportunity to present a brief synopsis of the evolution of our understanding of this condition and to review the modern literature on it. PMID- 11779344 TI - ENT Comparative Audit Meeting at the Royal College of Surgeons of England. PMID- 11779345 TI - Synergistic antiadipogenic effects of HIV type 1 protease inhibitors with tumor necrosis factor alpha: suppression of extracellular insulin action mediated by extracellular matrix-degrading proteases. AB - Long-term use of HIV-1 protease inhibitors (PIs) is associated with a lipodystrophy syndrome. To delineate the associated mechanisms, adipogenesis was determined in 3T3-L1 cells in the presence or absence of either indinavir (2-50 microg/ml) or ritonavir (0.4-10 microg/ml). A concentration-dependent decrease in both lipid (4-59%) and triglyceride (11-49%) levels was seen after 10 days of exposure. Simultaneous treatment with TNF-alpha showed a synergistic suppression in lipid levels by 45-95% at 10 U/ml and almost complete suppression at 100 U/ml. The effect of PIs on insulin-induced lipogenesis was monitored by [(14)C)]glucose incorporation into lipids, which was suppressed by 21-86% in a concentration dependent manner. Insulin-sensitizing agent, troglitazone (80 and 400 nM), effectively blocked the PI-mediated adipogenic suppression. Preadipocyte factor 1 gene (pref-1) expression, as monitored by RT-PCR, was downregulated (4- to 6 fold) within 48 hr after insulin stimulation; however, a smaller decrease (1.2- to 1.8-fold) was observed in PI-exposed cells. The decrease in proteolytic activity of matrix metalloproteases (MMP-2 and MMP-9) during adipogenesis was reversed on exposure to the PIs. Similarly, the plasminolytic activity was increased and plasminogen activator inhibitor (PAI) activity was decreased in supernatants from PI-treated cells. The insulin-mediated induction (3- to 4-fold) of PAI-1 and PAI-2 message was suppressed on exposure to PIs, which was reversed by troglitazone treatment. Thus, the HIV-1 PIs may suppress adipogenesis by disrupting the concerted actions of host proteases that regulate ECM integrity required for initiation of differentiation. PMID- 11779346 TI - CD4-independent infection of human B cells with HIV type 1: detection of unintegrated viral DNA. AB - Although B lymphocytes are a major constituent of lymphoid organs and acquire a significantly altered phenotype and function in HIV-infected individuals, it remains unclear whether CD4-negative B cells are a susceptible host for viral entry and long-term productive infection. We screened a number of Epstein-Barr virus (EBV)-positive and-negative Burkitt's lymphoma (BL) B cell lines as well as subpopulations of normal B cells that include tonsillar naive and germinal center/memory B cells for the expression of HIV-1 receptors CD4, CXCR4, and CCR5. Cell lines and resting or activated normal B cells lacked CD4 and CCR5 but expressed CXCR4. We demonstrate HIV-1 infection of a CD4-negative, EBV-negative (BL) cell line, CA46, which remained productively infected yet noncytopathic for more than 36 months in culture. HIV-1 (HTLV-III(B)) infection of CA46 cells was mediated through CXCR4 in a CD4-independent manner and correlated with upregulation of the expression of B cell activation markers CD23 and CD95 (Fas receptor). Despite Fas receptor expression, HIV-1-infected CA46 cells remained resistant to Fas-mediated cell death. CA46-derived, CD4-independent viral isolates were proficient in infecting and causing syncytium formation in Molt4 T cells. The HIV-1 genomic organization in persistently infected CA46 clones was found to be predominantly unintegrated linear and circular DNA. Importantly, naive and germinal center/memory B cells could also be infected by HIV-1 in a CD4 independent manner. Although these B cell subpopulations expressed moderate to high levels of CXCR4, they required activation through CD40 and interleukin 4 receptor for infection. These findings point to B cells as an additional HIV-1 target and suggest a structural evolution of the HIV-1 genome responsible for CD4 independent and noncytopathic infections. PMID- 11779347 TI - Decay of HIV type 1 DNA and development of drug-resistant mutants in patients with primary HIV type 1 infection receiving highly active antiretroviral therapy. AB - The present study was aimed at describing the effect of highly active antiretroviral therapy (HAART) in 10 patients with primary HIV infection (PHI). Clearance rates of HIV RNA and HIV DNA in peripheral blood as well as the preexistence and the emergence of drug-resistant strains of HIV were determined over 52 weeks of treatment. The data indicate that HAART is able to induce a suppression of plasma viral load together with a significant decrease, but not a suppression, of peripheral blood mononuclear cell-associated proviral DNA in PHI subjects. Analysis of drug-resistant strains revealed that three PHI patients, showing a complete virologic response, developed mutations in the pol gene, thus suggesting that a persistent residual virus replication exists despite a sustained suppression of plasma viremia. PMID- 11779348 TI - Effects of norepinephrine, HIV type 1 infection, and leukocyte interactions with endothelial cells on the expression of matrix metalloproteinases. AB - The expression of matrix metalloproteinases (MMPs) associated with AIDS-related cardiomypathies and cocaine abuse was examined in an in vitro coculture model. Human peripheral blood mononuclear cells (PBMCs), HIV infected or uninfected, were placed in coculture with primary human cardiac microvascular endothelial cells (HMVEC-C) in the presence or absence of the cocaine-inducible catecholamine norepinephrine (NE). Culture supernatants were assayed for MMP-1, -2, -3, -7, -9, and -13, and for tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-2, by enzyme-linked immunosorbent assay. Low levels of constitutively expressed MMP-1 and -2 were detected in individual cultures of HMVEC-C and PBMCs. NE did not induce MMP or TIMP expression by HMVEC-C and caused modest increases (3- to 4 fold) in MMP-1 and -2 by uninfected PBMCs. Increased levels of NE-induced MMP-1 (5-fold) and MMP -2 (15-fold) were detected in cocultures of HMVEC-C and uninfected PBMCs. HIV infection enhanced MMP-1 (46-fold) and MMP-2 (48-fold) and active MMP-7 (33-fold) and MMP-9 (50-fold) by PBMCs. Coculture of HIV-infected PBMCs with HMVEC-C increased MMP-1 (110-fold) and MMP-2 (307-fold) but not active MMP-7 and -9. The combination of NE, HIV infection, and coculture increased MMP-1 (126-fold) and MMP-2 (467-fold), and active MMP-7 (65-fold) and MMP-9 (75-fold). MMP-3 or-13 was not detected in any of the treatment groups and TIMP-1 and -2 appeared inversely proportional to the observed levels of MMPs. These results suggest that HIV infection, NE, and leukocyte endothelial interactions demonstrate separate and overlapping cooperative effects on the regulation of expression of TIMPs and MMPs associated with AIDS-related cardiomyopathies. PMID- 11779349 TI - Small variations in the length of the cytoplasmic domain of the simian immunodeficiency virus transmembrane protein drastically affect envelope incorporation and virus entry. AB - Simian immunodeficiency viruses (SIVs) have an envelope (Env) glycoprotein with an unusually long cytoplasmic domain of 164 amino acids. In this article, we have characterized a series of SIV Env truncation mutants in which the cytoplasmic domain was progressively shortened from its carboxyl terminus by 20 amino acids. Expression by means of the vaccinia virus system showed that all of the SIV Env mutants were expressed and processed into the surface and transmembrane (TM) subunits. When the ability of the Env mutants to associate with SIV Gag particles was examined, we found that deletion of 20 to 80 residues from the carboxyl terminus of the SIV TM cytoplasmic tail abrogated the incorporation of the Env glycoprotein into particles. By contrast, further truncation of the SIV TM protein by 100 to 140 amino acids restored the ability of the Env protein to associate with Gag particles. Interestingly, mutants bearing a 44- or 24-amino acid cytoplasmic domain were incorporated at levels significantly higher than those of the wild-type Env. Single-cycle infectivity assays showed that Env mutants bearing cytoplasmic tails of 144 to 64 amino acids were highly inefficient at mediating virus entry. By contrast, truncation of the cytoplasmic domain to 44 or 24 amino acids drastically enhanced virus infectivity with respect to that conferred by the full-length Env protein. Our results demonstrate that small variations in the length of the SIV Env cytoplasmic domain dramatically influence Env-mediated viral functions. PMID- 11779350 TI - Rapid alternation of drug therapy is highly efficient in suppressing the emergence of mutant drug-resistant HIV strains in cell culture. AB - We evaluated the effect of drug alternation on human immunodeficiency virus type 1 (HIV-1) suppression and emergence of resistant virus strains in CEM cell cultures. Rapid, that is, twice weekly, alternation of lamivudine and nevirapine (at 0.1 microg/ml) at the time of each subcultivation resulted in a long-term suppression of virus replication (up to 18 subcultivations, or 9 weeks) and eventual sterilization of the cell cultures. Under similar experimental conditions mutant virus rapidly emerged (within two or three subcultivations) when the same drug (lamivudine or nevirapine) was applied throughout. The longer the HIV-1-infected cell cultures were exposed to the same drug before shifting to the other drug, the shorter the time period for mutant virus to appear. Those virus strains that eventually emerged under suboptimal alternating drug therapy harbored a combination of lamivudine- and nonnucleoside reverse transcriptase (RT)-specific mutations in the RT gene. When extrapolated to the clinical setting, our data indicate that the efficacy of HIV-1 therapy may be markedly improved by rapid alternation of drug cocktails before detectable evidence of resistance development as compared with drug cocktail alternation after the first signs of drug resistance become visible. PMID- 11779351 TI - Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy. AB - The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia. PMID- 11779352 TI - Postattachment neutralization of a primary strain of HIV type 1 in peripheral blood mononuclear cells is mediated by CD4-specific antibodies but not by a glycoprotein 120-specific antibody that gives potent standard neutralization. AB - De novo infecting HIV-1 or virus released from an infected cell in vivo attaches relatively quickly to a target cell, but the rate of fusion-entry of such virus is slow, with 50% entry taking > or =2 hr. It is thus desirable that antibodies stimulated by any vaccine or given in immunotherapy are able to neutralize not only free virus, but also virus attached to the target cell. Here we investigated postattachment neutralization (PAN) of a primary HIV-1 strain (JRCSF) in peripheral blood mononuclear cells and of a T cell line-adapted strain (IIIB) in C8166 T lymphoblastoid cells, using the highly potent gp120-specific human monoclonal b12 monoclonal IgG, and monoclonal antibodies specific for the CD4 primary cell receptor. In addition, we improved the experimental protocols of related studies by using a pulse of antibody, thus avoiding the complication of neutralizing progeny virus. We found that b12 IgG PAN was inefficient, with PAN of IIIB needing a 1000-fold greater concentration of antibody than was required for standard neutralization, and PAN of JRCSF being detected erratically only at 4 degrees C and unphysiologically high concentrations (300 microg/ml). Nonetheless, under identical conditions a 10-microg/ml pulse of the CD4-specific MAb Q4120 gave up to 99% PAN of JRCSF, and more than 95% even when added 3 hr after infection at 37 degrees C. Possible mechanisms by which PAN by CD4- specific antibodies is mediated are discussed. We suggest that such anti-CD4 antibodies should be considered as a component of HIV-1 immunotherapy. PMID- 11779353 TI - Importation of multiple HIV type 1 strains into West Papua, Indonesia (Irian Jaya). AB - HIV-1 from 16 sexually transmitted disease clinic patients in Timika, West Papua, Indonesia was amplified by RT-PCR and subtyped by a combination of envelope and gag region heteroduplex mobility analysis (HMA) and direct PCR DNA sequencing. HMA showed the presence of 14 subtype E (CRF01_AE) and 2 subtype B HIV-1. Phylogenetic analysis of a 540-bp V3-V4 region of gp120 showed that 9 of 10 CRF01_AE variants clustered tightly with a median distance of 1.3% (range, 0.5 to 2.2%) whereas 1 CRF01_AE variant diverged significantly from the others (median distance, 10.7%; range, 10.1 to 11.8%). One subtype B virus envelope was typical of United States/European strains whereas the other appeared to be related to Thai subtype B' variants. These results reflect the independent introduction of multiple HIV-1 strains into West Papua, with the rapid spread in the majority of infected patients tested of a single strain of HIV-1E (CRF01_AE). PMID- 11779354 TI - Genetic analysis of HIV type 2 from Ghana and Guinea-Bissau, West Africa. AB - The phylogenetic variability of part of the long terminal repeat (LTR) region of HIV-2 strains isolated in 1995 from five individuals residing in Bissau, the capital city of Guinea-Bissau, and collected from seven persons from Kumasi, Ghana in 1996-1997, was analyzed. All Guinean samples and all but one Ghanaian sample clustered with HIV-2 subtype A. One Ghanaian sample (14%) was classified as HIV-2 subtype B. This study adds to previous reports on HIV-2 subtype distribution in West Africa indicating local prevalence of HIV-2 subtype B in Ivory Coast and neighboring Ghana. PMID- 11779355 TI - Sequence and phylogeny of HERV-W pol fragments. AB - A new human endogenous retroviral family (HERV-W) has been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Using the PCR approach with a human monochromosomal somatic cell hybrid DNA panel, 24 pol fragments of the HERV-W family from chromsomes 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 20, 21, X, and Y were identified and analyzed. They showed a high degree of nucleotide sequence similarity (89.3 91.3%) with that of the HERV-W. Translation of the pol fragments showed no frameshift and termination codon by deletion/insertion or point mutation in some clones: HWP4-1, HWP4-2 from chromosome 4, and HWPX-1 from chromosome X. Phylogenetic analysis of the HERV-W family indicates that the pol fragments have evolved independently among chromosomes or represent separate integration events during primate evolution. PMID- 11779356 TI - Genetic characterization of HIV type 1 gag p17 matrix genes in isolates from infected mothers lacking perinatal transmission. AB - The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) were analyzed from three nontransmitting mothers (mothers who failed to transmit HIV-1 to their infants in the absence of antiretroviral therapy), including multiple deliveries in the case of mother 3. There was a low degree of heterogeneity of gag p17 matrix sequences in nontransmitting mothers compared with our previously analyzed mother-infant pairs' sequences. Whereas most of the functional domains essential for p17 matrix function were generally conserved, the polymerization site was less conserved. Several amino acid motifs, including KIEEEQN (positions 103-109) at the major antibody-binding site, were variable and the C-terminal 6 mer QVSQNY, a lysine or glutamine at position 15, an alanine at position 54, a lysine at position 76, a valine at position 104, and an aspartic acid at positions 102 and 121 were conserved in nontransmitting mothers' sequences compared with transmitting mothers' sequences. Phylogenetic analyses of 82 p17 matrix sequences revealed distinct clusters for each nontransmitting mother. Some of these motifs in gag p17 matrix sequences that are present in nontransmitting mothers and absent in transmitting mothers could be used as new targets for the development of preventive strategies for perinatal transmission. PMID- 11779357 TI - Conserved domains of subtype C nef from South African HIV type 1-infected individuals include cytotoxic T lymphocyte epitope-rich regions. AB - We have characterized 43 nef sequences from subtype C HIV-1-infected South Africans and compared deduced amino acid sequences with other subtypes to identify areas of conservation. Our Nef amino acid sequences were aligned with a consensus subtype B, HXB2 reference strain and a consensus subtype C sequence. All were found to be highly homologous to subtype B in the central region of Nef, but more variable at the N and C termini of the molecule. Alignment of a consensus amino acid sequence generated from South African subtype C Nef with subtypes A, B, and D underscores cross-clade conservation in the central domain of the molecule. This domain is also rich in previously described cytotoxic T lymphocyte (CTL) epitopes that are restricted by commonly found HLA molecules in the South African population. PMID- 11779359 TI - Fragmentation of short single DNA strands by 1-30 eV electrons: dependence on base identity and sequence. AB - PURPOSE: To investigate the dependence of base identity and sequence on the damage induced by low-energy (1-30 eV) electron impact on a short single strand of DNA. MATERIALS AND METHODS: Monolayers of homogeneous nonamers of deoxycytidine and thymidine (dCy9 and T9) and heterogeneous nonamers of thymidine substituted with 33 and 66% of deoxycytidine (dCy3-T6 and dCy6-T3) were chemisorbed onto a gold substrate. They were bombarded under ultrahigh vacuum conditions by a 1-30 eV electron beam. Neutral fragments desorbed from the films were detected by a mass spectrometer. From partial pressure measurements, the effective cross-section (ECS) per base for desorption of various fragments was estimated. RESULTS: CN, OCN and/or H2NCN were the major neutral species observed to desorb in the present experiments. A small contribution of 55 amu neutral species, tentatively attributed to CH3CCO, were only detected from fragmentation of oligonucleotides containing thymine. The total ECS per base estimated for the CN, OCN and CH3CCO species production from fragmentation of dCy9, dCy6-T3, dCy3 T6 and T9 at 12 eV incident electron energy were (3.4, 2.0, 2.9 and 2.3) x 10( 17) cm(2), respectively. The incident electron energy dependence of ECS for desorption of these fragments exhibited structures <20 eV, which are characteristic of transient anion formation. CONCLUSIONS: At incident electron energies <20 eV, neutral fragment desorption arise from dissociation of the DNA bases, principally via dissociative electron attachment and/or decay of the transient anion into a dissociative electronic excited state of the base. Non resonant mechanisms (e.g. direct dipolar dissociation) mostly control the fragmentation processes >20 eV. From comparison of the electron energy dependence of the ECS for base fragmentation in the homo- and heteronucleotides, it is concluded that damage to a short DNA strand is dependent on base identity, sequence and electron energy. PMID- 11779358 TI - Characterization of CDKN1A (p21) binding to sites of heavy-ion-induced damage: colocalization with proteins involved in DNA repair. AB - PURPOSE: To determine an association of locally accumulated CDKN1A and DNA repair proteins at the sites of heavy-ion traversals. MATERIALS AND METHODS: CDKN1A, PCNA, DNA-PK, hMre11 and Rad50 were investigated for their subnuclear localization after irradiation with heavy-ions using immunocytochemical staining and confocal laser-scanning microscopy. Human fibroblasts (normal diploid or XPA, ATM- or NBS1-deficient lines and HPV16 E6-transfected cells) were used. RESULTS: CDKN1A formed nuclear foci in G0/G1 normal human fibroblasts at the sites of particle traversal. Foci were persistent over hours and vanished after treatment with DNase-I. Formation of foci also occurred in NBS1- or ATM-deficient lines and in cells functionally abrogated for TP53. In normal fibroblasts, CDKN1A foci colocalized with particle-induced foci of the hMre11 and Rad50 proteins. However, only CDKN1A relocalization was observed in irradiated NBS1 cells. PCNA foci temporarily colocalizing with CDKN1A were also detected in normal fibroblasts after exposure to heavy-ions. In contrast, no radiation-induced subnuclear relocalization was found for DNA-PK. CONCLUSIONS: CDKN1A foci arise rapidly at sites of localized DNA damage induced by heavy-ions and are associated with the chromatin. Evidence is provided that localization of CDKN1A to foci is not dependent on functional TP53 and occurs independently of the formation of the hMre11/Rad50/NBS1 complex. The data support a yet unknown role of CDKN1A in sensing or early processing of radiation-induced DNA lesions. PMID- 11779360 TI - Hydroxyl radical probe of protein surfaces using synchrotron X-ray radiolysis and mass spectrometry. AB - A new approach is reported that combines synchrotron radiolysis and mass spectrometry to probe the structure of proteins. Hydroxyl radicals produced upon the radiolysis of protein solutions using synchrotron light modify amino acid side-chains on millisecond timescales. This results in the formation of stable oxidation products where the level of oxidation at the reactive residues is influenced by the accessibility of their side-chains to the bulk solvent. The aromatic and sulphur-containing residues have been found to react preferentially in accord with previous peptide studies. The sites of oxidation have been determined by tandem mass spectrometry. The rate of oxidation at these reactive markers has been measured for a number of proteolytic peptides as a function of exposure time based on the relative proportion of modified and unmodified peptide ions detected by mass spectrometry. Oxidation rates correlate closely with a theoretical measure of the accessibility of residue side-chains to the solvent in the native protein structure. This approach can distinguish the relative accessibility of the tryptophan residue side-chains of lysozyme at positions 62 and 123 from each other and all other tryptophan residues, and phenylalanine at position 34 from phenylalanine residues at positions 3 and 38 based upon their rates of oxidation. PMID- 11779361 TI - Protein synthesis-dependent apoptotic signalling pathway in X-irradiated MOLT-4 human leukaemia cell line. AB - PURPOSE: To demonstrate whether protein synthesis is required for ionizing radiation-induced apoptosis through activation of caspases in human leukaemia cell line MOLT-4, the effects of a protein synthesis inhibitor, cycloheximide, on the apoptotic signalling pathway including the activation of caspase family and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and the expression of Fas/CD95/APO-1 (Fas) were examined in X-irradiated MOLT-4 cells. MATERIALS AND METHODS: MOLT-4 cells pretreated with 0.5 microg/ml cycloheximide for 1h were exposed to 7.5Gy of X-rays. The appearance of apoptosis, expression of Fas, activation of caspases-3, -8, -9, SAPK/JNK and AP-1, the release of mitochondrial cytochrome-C and the formation of death-induced signalling complex (DISC) between Fas and the Fas-associated death domain (FADD) were measured by fluorescence microscopy, Western blotting, flow cytometry, gel shift assay and immunoprecipitation, respectively. RESULTS: Nuclear fragmentation and chromatin condensation were observed at 6 h after X-irradiation and gradually increased up to 12 h. These phenomena were significantly attenuated by cycloheximide. Cycloheximide also inhibited the activation of caspases and AP-1, the expression of Fas, the formation of DISC and the release of cytochrome-C, but not the activation of SAPK/JNK in X-irradiated MOLT-4 cells. CONCLUSION: These results indicate that apoptosis of X-ray-induced MOLT-4 cells is dependent on the activation of caspases regulated by de novo protein synthesis through SAPK/JNK activation. PMID- 11779362 TI - Differential response of tumor cells and normal fibroblasts to fractionated combined treatment with topotecan and ionizing radiation. AB - PURPOSE: The impact of the topoisomerase-I inhibitor topotecan (Hycamtin) as a single agent or in combination with ionizing radiation on clonogenic cell survival has been evaluated in three tumor cell lines and in normal fibroblasts. Both agents have been applied in a fractionated scheme in order to assess clinically relevant conditions. MATERIALS AND METHODS: Cell inactivation was investigated in human glioblastoma cell lines U118 and U138, lung carcinoma cell line A549 and normal fibroblasts of the skin (HSF6) and lung (CCD32) using the colony formation assay. RESULTS: The glioblastoma cell lines were highly sensitive to the drug, whereas normal fibroblasts were much less sensitive. A significant antagonistic effect of the drug combined with irradiation was found for normal fibroblasts, while glioblastoma cells showed no evidence of interaction, indicating additivity. A549 cells showed a biphasic response to topotecan alone and in combination with irradiation, suggesting induction of resistence to the drug. CONCLUSION: Differential effects of combined topotecan/radiation treatment were detected between cells of normal tissue and tumor cells, being antagonistic in fibroblasts of the skin and lung, but not in tumor tissue, especially in glioblastoma cells. PMID- 11779363 TI - Radiation doses to non-Hodgkin's lymphoma cells and normal bone marrow exposed in vitro. Comparison of an alpha-emitting radioimmunoconjugate and external gamma irradiation. AB - PURPOSES: The alpha-emitting radionuclide 211At conjugated to the CD20 targeting chimeric monoclonal antibody rituximab was studied to: (a) Estimate radiation dose components to lymphoma and bone marrow (BM) cells exposed in vitro. (b) Calculate the mean absorbed radiation doses in various normal tissues of mice following intravenous injection. MATERIALS AND METHODS: B-lymphoma cells (RAEL) and normal human BM cells were incubated with increasing concentrations of the radioimmunoconjugate. Based on binding kinetics and on measured cellular and nuclear diameters, the radiation doses were calculated using microdosimetric methods. RESULTS: Targeting of 211At-rituximab to RAEL cells was extensive and stable compared with the binding to BM cells. The absorbed radiation doses from cell-bound activity at an initial activity concentration of 10 kBq ml(-1) were 0.645 and 0.021 Gy to RAEL and BM cells, respectively. In comparison, the contribution from unbound conjugate in the medium during 1h exposure was 0.042 and 0.043 Gy. The D(0) value for RAEL cells was 0.55 Gy, but only 0.34 Gy for BM cells, whereas corresponding D(0) values were 0.72 and 1.21 Gy after a single exposure to external 60Co gamma-rays. Mean absorbed doses of 1.31, 0.48 and 0.36 Gy for blood, lungs and heart were calculated in mice injected with 5.4kBq g(-1) of 211At-rituximab. CONCLUSION: Despite the higher inherent sensitivity of the BM cells to the alpha-irradiation, there was, related to the radioactivity concentrations of 211At-rituximab, several logs greater cell kill in RAEL cells, illustrating the tumour-specific nature of the targeting. PMID- 11779366 TI - Childhood sexual abuse and sexually transmitted diseases in adults: a review of and implications for STD/HIV programmes. AB - Childhood sexual abuse (CSA) has been linked to a variety of health problems in adolescence and adulthood, including risky sexual behaviour and sexually transmitted diseases (STDs). This article reviews the literature, including findings from a recent intervention study of high-risk, adult women and offers suggestions for professionals working in STD/HIV prevention. PMID- 11779365 TI - Efficacy of preventive human papillomavirus vaccination. AB - Interplay between host immune system and expression of human papillomavirus (HPV) early (E) and late (L) genes during infection has a central role in the surveillance of virus-induced neoplastic cervical lesions. Recently, new features of this interplay have been discovered. However, not enough is yet known of the relative roles of different E and L proteins, human lymphocyte antigens (HLAs) and specific co-factors in the natural history of these lesions in order to guarantee efficacy of preventive HPV vaccination. The ultimate knowledge can only be provided by phase III/IV vaccination trials which are starting in the near future. The present review attempts to answer one fundamental question: which of the vaccine candidates is likely to be most successful. PMID- 11779367 TI - Clinical uses of herpes simplex virus type-specific serology. AB - Type-specific serological tests to distinguish between infection with herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) have largely been used for studies which have contributed to our knowledge of the epidemiology and natural history of these infections. Such tests could be used as diagnostic tools in clinical situations provided that clinician and patient are aware of the test characteristics, which may result in false negative and false positive results. The use of serological tests in the screening of populations or sub populations, such as pregnant women, has been advocated to attempt to halt the worldwide spread of the infection. However, there is little evidence currently to support this strategy. PMID- 11779368 TI - Factors involved in clearance of genital warts. AB - Consecutive patients with first presentation of external anogenital warts had the location, duration at presentation, number of warts and wart area, age, smoking and sun bed use, and presence of coexistent sexually transmitted infections (STIs) recorded. The number of treatment episodes, and number of weeks, to clear the warts were documented. Number of warts and wart area at presentation were associated with time and number of treatments to clear. Those with 1-3 warts required significantly fewer treatment episodes and less time to clear than those with 11-41 warts, as did those with warts area 2-19 mm(2) compared with wart area 100-1038 mm(2). Using survival analysis, the number of warts was significant for the number of treatments and weeks to clear. The hazard ratio for clearance with double the number of warts after 4 treatments was 0.53 (95% confidence interval [CI] 0.37-0.76), and at 4 weeks was 0.70 (0.45-0.86). The clearance rates in non smokers compared with smokers were higher, but not significantly different. Wart burden at presentation is an indicator of time to clearance. The number of warts is the best predictor - fewer warts results in earlier clearance. PMID- 11779369 TI - The detection of Chlamydia trachomatis by DNA amplification methods in urine samples from men with urethritis. AB - Our objective was to compare 3 deoxyribonucleic acid (DNA) amplification methods for the diagnosis of chlamydial infection with an enhanced enzyme immunoassay (EIA) method for antigen detection in urine samples, from men with non-gonococcal urethritis (NGU) attending a busy inner city genitourinary medicine centre. Urethral swabs and urine samples were collected from 346 male patients with NGU attending the clinic. All swabs and urines were tested for chlamydial infection (CT) using the EIA (Dako PCE immunoassay). Three aliquots of the urine samples were stored immediately at -70 degrees C for subsequent testing by: Amplicor polymerase chain reaction (PCR) (Hoffmann-La Roche, Switzerland); the amplified Chlamydia trachomatis assay (AMP CT) using transcription mediated amplification (TMA) (GenProbe, USA); and BDProbeTecET using the strand displacement assay (SDA) (Becton Dickinson, USA). The positive rate for the 3 amplified assays PCR, TMA and SDA (on urine) was 88/346 (25.4%), 80/346 (23.1%) and 88/346 (25.4%), respectively compared to 56/346 (16.2%) by EIA on urethral swabs, the current means of diagnosis in this laboratory. Thirty-one samples were positive in 2 or more of the amplification assays but negative in the EIA, 50 positives (53% sensitivity) detected in the urine samples by the EIA assay were detected by all 3 of the amplified assays. Three samples were positive by PCR only, 5 were positive by TMA only and 7 were positive by SDA only. DNA amplification assays are superior to standard immunoassays for the diagnosis of C. trachomatis infections in urine samples. Urine samples are suitable for use in these amplified assays to detect C. trachomatis. Freezing of samples before testing reduces the rate of inhibition reported in other published studies. PMID- 11779370 TI - Development of a heminested polymerase chain reaction assay for the detection of Haemophilus ducreyi in clinical specimens. AB - Detection of Haemophilus ducreyi in genital ulcer specimens by culture lacks sensitivity. To enhance detection, a heminested polymerase chain reaction (PCR) assay was developed targeting the nucleotide sequence of a gene, designated p27, which encodes for a 27 kDa H. ducreyi-specific protein. The p27 PCR assay detected all (37/37) H. ducreyi strains tested and gave no amplified product from DNA extracts of any of 31 other microorganisms, from 30 non-genital ulcer specimens, or from 29 urethral and vaginal swab specimens collected from non chancroid STD patients. In genital ulcer disease specimens, compared to combined positive results obtained by culture and a previously described PCR assay, the p27 PCR assay showed a sensitivity of 91% (48/53). The p27 PCR assay provides a specific and a sensitive detection of H. ducreyi in clinical specimens. PMID- 11779371 TI - Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test. AB - Recent evidence suggests that 10 microg cosyntropin test has higher sensitivity for detecting hypothalamus-hypophysis-adrenal axis (HHA-A) dysfunction. Our objective was to determine prevalence of glucocorticoid insufficiency with the 10 microg cosyntropin test and the level of the HHA-A defect. One hundred and four HIV-infected patients underwent the 10 microg cosyntropin test. In abnormal and borderline respondents, insulin-induced hypoglycaemia test and human corticotropin releasing hormone test were used to confirm and localize the level of the HHA-A defect. Thirty-two patients with HIV infection and 72 with AIDS were identified. Prevalence of glucocorticoid insufficiency by the 10 microg cosyntropin test was 21.2%. By clinical categories, the frequency in AIDS and HIV infection patients was 26.4% and 9.4%, respectively. Confirmed glucocorticoid insufficiency by insulin-induced hypoglycaemia test was found in 16 out of 19 cases. Twelve cases had primary glucocorticoid insufficiency, 7 had secondary glucocorticoid insufficiency and 3 were false positive. In conclusion, adrenocortical dysfunction occurs in approximately 20% of the cases with HIV disease. Clinical findings commonly occurring in HIV disease as well as adrenocortical insufficiency are not reliable indicators for performing adrenocortical laboratory assessment. Our results suggest screening all AIDS patients with the 10 microg cosyntropin test. PMID- 11779372 TI - Sexually transmitted infections in Western Europe--from the North Cape to the Black Sea. PMID- 11779373 TI - Sexually transmitted infections in Italy: an overview. AB - In Italy more than 240,000 and 500,000 cases of gonorrhoea and syphilis, respectively, were reported in 1936 but the incidence progressively fell to about 200-300/year by the early 1990s; data available now are probably 100-150% underestimated. An inefficient notification system, diversion of public funding to other fields, and the progressive decline in importance of dermatovenereological centres are responsible for this decline. The advent of the HIV epidemic (with more than 47,000 AIDS reported cases) has drained most public health resources away from the very limited interventions for the control of traditional sexually transmitted infections (STIs). This has led some groups to attempt alternative approaches to the HIV/STI prevention and treatment policies; the potential of these new experiences need to be assessed. A change in culture of the medical body politic is now essential in order to support medical professionals, administrators and programme managers seeking to implement proper STI control programmes. PMID- 11779374 TI - Care of sexually transmitted infections in the Nordic countries. AB - This article presents an overview of the epidemiology and control of sexually transmitted infections (STIs) in the Nordic countries. These countries have succeeded in controlling gonorrhoea and syphilis, and the incidence of HIV infection is low. However, during the last few years the incidence of all STIs has increased, although from very low levels. Genital chlamydial infection is still prevalent, and is also increasing. Dermatovenereologists are responsible for the specialized care of STIs, but family doctors and gynaecologists are responsible for the management of a great portion of STIs. PMID- 11779375 TI - Sexually transmitted infections in Turkey. AB - Turkey is a Moslem country where lay knowledge regarding sexually transmitted infections (STIs) is poor. Surveillance arrangements are limited, and frequently ignored, with the result that the true incidence of STIs is unknown. The prevalence of syphilis is definitely increasing, and probably that of the other infections is too. Modern diagnostic techniques are not widely deployed and there is little standardization of medical arrangements. However, there has been a high level of governmental involvement in HIV prevention in recent years and it is now believed that most HIV transmission in Turkey is by the heterosexual route. PMID- 11779376 TI - Gonococcal ophthalmia treated with ciprofloxacin. AB - Neisseria gonorrhoeae infection in the eye and its treatment with ciprofloxacin is presented. PMID- 11779377 TI - The HIV epidemic in Kinshasa, Democratic Republic of Congo. PMID- 11779379 TI - The origin and control of pandemic Influenza. Papers of a discussion meeting held at the Royal Society. April 25-26. London, United Kingdom. PMID- 11779380 TI - Emergence of influenza A viruses. AB - Pandemic influenza in humans is a zoonotic disease caused by the transfer of influenza A viruses or virus gene segments from animal reservoirs. Influenza A viruses have been isolated from avian and mammalian hosts, although the primary reservoirs are the aquatic bird populations of the world. In the aquatic birds, influenza is asymptomatic, and the viruses are in evolutionary stasis. The aquatic bird viruses do not replicate well in humans, and these viruses need to reassort or adapt in an intermediate host before they emerge in human populations. Pigs can serve as a host for avian and human viruses and are logical candidates for the role of intermediate host. The transmission of avian H5N1 and H9N2 viruses directly to humans during the late 1990s showed that land-based poultry also can serve between aquatic birds and humans as intermediate hosts of influenza viruses. That these transmission events took place in Hong Kong and China adds further support to the hypothesis that Asia is an epicentre for influenza and stresses the importance of surveillance of pigs and live-bird markets in this area. PMID- 11779381 TI - Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus. AB - The Spanish influenza pandemic of 1918-1919 caused acute illness in 25-30% of the world's population and resulted in the death of 40 million people. The complete genomic sequence of the 1918 influenza virus will be deduced using fixed and frozen tissues of 1918 influenza victims. Sequence and phylogenetic analyses of the complete 1918 haemagglutinin (HA) and neuraminidase (NA) genes show them to be the most avian-like of mammalian sequences and support the hypothesis that the pandemic virus contained surface protein-encoding genes derived from an avian influenza strain and that the 1918 virus is very similar to the common ancestor of human and classical swine H1N1 influenza strains. Neither the 1918 HA genes nor the NA genes possessed mutations that are known to increase tissue tropicity, which accounts for the virulence of other influenza strains such as A/WSN/33 or fowl plague viruses. The complete sequence of the nonstructural (NS) gene segment of the 1918 virus was deduced and tested for the hypothesis that the enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. The results from these experiments were inconclusive. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help to elucidate how pandemic influenza strains emerge and what genetic features contribute to their virulence. PMID- 11779382 TI - Reverse genetics approach towards understanding pathogenesis of H5N1 Hong Kong influenza A virus infection. AB - In 1990, Palese and colleagues established a method (reverse genetics) that allowed one to generate influenza virus containing a gene segment derived from cloned cDNA. Although this method contributed tremendously to our understanding of influenza pathogenesis, the requirement of helper viruses limited its use in many experimental settings. Recently, we and others established systems for the generation of influenza viruses entirely from cloned cDNAs. These systems require only DNA cloning and transfection techniques, and can therefore be easily implemented by laboratories working in the fields of molecular biology and virology. Thus, for the first time, a system is now available that allows highly efficient generation of influenza virus without technical limitations. Using this technology, we generated the same strain of H5N1 influenza viruses that caused an outbreak in Hong Kong in 1997, killing six people. PMID- 11779383 TI - The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant. AB - Published analyses of the sequences of three genes from the 1918 Spanish influenza virus have cast doubt on the theory that it came from birds immediately before the pandemic. They showed that the virus was of the H1N1 subtype lineage but more closely related to mammal-infecting strains than any known bird infecting strain. They provided no evidence that the virus originated by gene reassortment nor that the virus was the direct ancestor of the two lineages of H1N1 viruses currently found in mammals; one that mostly infects human beings, the other pigs. The unusual virulence of the virus and why it produced a pandemic have remained unsolved. We have reanalysed the sequences of the three 1918 genes and found conflicting patterns of relatedness in all three. Various tests showed that the patterns in its haemagglutinin (HA) gene were produced by true recombination between two different parental HA H1 subtype genes, but that the conflicting patterns in its neuraminidase and non-structural-nuclear export proteins genes resulted from selection. The recombination event that produced the 1918 HA gene probably coincided with the start of the pandemic, and may have triggered it. PMID- 11779384 TI - The so-called Great Spanish Influenza Pandemic of 1918 may have originated in France in 1916. AB - This discussion piece examines the likely epicentre of the influenza pandemic of 1918-1919. Contrary to previous studies that have proposed a Chinese origin, there is documentation that suggests that, in this instance, the virus spread eastwards to China from Europe. Although more recent oubreaks of influenza have undoubtedly had an Oriental origin, the evidence indicates that future outbreaks could conceivably arise anywhere in the world. PMID- 11779385 TI - The evolution of human influenza viruses. AB - The evolution of influenza viruses results in (i) recurrent annual epidemics of disease that are caused by progressive antigenic drift of influenza A and B viruses due to the mutability of the RNA genome and (ii) infrequent but severe pandemics caused by the emergence of novel influenza A subtypes to which the population has little immunity. The latter characteristic is a consequence of the wide antigenic diversity and peculiar host range of influenza A viruses and the ability of their segmented RNA genomes to undergo frequent genetic reassortment (recombination) during mixed infections. Contrasting features of the evolution of recently circulating influenza AH1N1, AH3N2 and B viruses include the rapid drift of AH3N2 viruses as a single lineage, the slow replacement of successive antigenic variants of AH1N1 viruses and the co-circulation over some 25 years of antigenically and genetically distinct lineages of influenza B viruses. Constant monitoring of changes in the circulating viruses is important for maintaining the efficacy of influenza vaccines in combating disease. PMID- 11779386 TI - The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin. AB - In 1982 we characterized the antigenic sites of the haemagglutinin of influenza A/PR/8/34, which is an influenza strain of the H1 subtype that was isolated from humans in 1934, by studying mutants which escaped neutralization by antibody. Four antigenic sites, namely Cb, Sa, Sb and Ca, were found to be located near the tip of the trimeric haemagglutinin spike. Based on the sequence of the haemagglutinin of the 1918 Spanish influenza, we can now specify the extent of divergence of antigenic sites of the haemagglutinin during the antigenic drift of the virus between 1918 and 1934. This divergence was much more extensive (40%) than the divergence (20%) in predicted antigenic sites between the 1918 Spanish influenza and an avian H1 subtype consensus sequence. These results support the hypothesis that the human 1918 pandemic originated from an avian virus of the H1 subtype that crossed the species barrier from birds to humans and adapted to humans, presumably by mutation and/or reassortment, shortly before 1918. PMID- 11779387 TI - Perspectives on antiviral use during pandemic influenza. AB - Antiviral agents could potentially play a major role in the initial response to pandemic influenza, particularly with the likelihood that an effective vaccine is unavailable, by reducing morbidity and mortality. The M2 inhibitors are partially effective for chemoprophylaxis of pandemic influenza and evidence from studies of interpandemic influenza indicate that the neuraminidase inhibitors would be effective in prevention. In addition to the symptom benefit observed with M2 inhibitor treatment, early therapeutic use of neuraminidase inhibitors has been shown to reduce the risk of lower respiratory complications. Clinical pharmacology and adverse drug effect profiles indicate that the neuraminidase inhibitors and rimantadine are preferable to amantadine with regard to the need for individual prescribing and tolerance monitoring. Transmission of drug resistant virus could substantially limit the effectiveness of M2 inhibitors and the possibility exists for primary M2 inhibitor resistance in a pandemic strain. The frequency of resistance emergence is lower with neuraminidase inhibitors and mathematical modelling studies indicate that the reduced transmissibility of drug resistant virus observed with neuraminidase inhibitor-resistant variants would lead to negligible community spread of such variants. Thus, there are antiviral drugs currently available that hold considerable promise for response to pandemic influenza before a vaccine is available, although considerable work remains in realizing this potential. Markedly increasing the quantity of available antiviral agents through mechanisms such as stockpiling, educating health care providers and the public and developing effective means of rapid distribution to those in need are essential in developing an effective response, but remain currently unresolved problems. PMID- 11779388 TI - Zanamivir: from drug design to the clinic. AB - The development of the neuraminidase inhibitors has revolutionized the management options for influenza. Zanamivir was the first such inhibitor to be approved for the treatment of influenza in humans. It is delivered by inhalation to the respiratory tract, which is the site of viral replication, in order to ensure immediate antiviral activity. Early treatment with zanamivir in clinical trials rapidly reduced the severity and duration of influenza symptoms and associated complications. Furthermore, chemoprophylaxis with zanamivir was shown to be effective in the prevention of influenza illness. To date, there is no evidence for the emergence of clinically significant zanamivir-resistant isolates. In conclusion, zanamivir offers a useful complementary strategy to vaccination in the effective management of influenza. PMID- 11779389 TI - Treatment of influenza with neuraminidase inhibitors: virological implications. AB - Evaluation of the emergence of influenza virus resistance to neuraminidase inhibitors (NAIs) is now demanded following experience with amantadinamines. Preliminary data have indicated that NAI-resistant virus is unlikely to emerge readily in the clinic and this is consistent with the difficulty experienced in selecting resistant virus in vitro. Resistance mutations can occur in both neuraminidase and haemagglutinin genes. The neuraminidase mutations are viral subtype specific and, therefore, clinically relevant subtypes must be employed for in vitro studies if pre-clinical data are to have predictive value. Haemagglutinin mutations generated in vitro are probably both subtype and cell culture system specific and, therefore, may not be predictive of clinical findings. Analysis of influenza-positive samples from NAI-treated patients in the clinical setting must include samples from late treatment time-points (day 4 and later) in order for resistant virus to be detected as in vitro studies and current clinical experience have indicated that resistant virus is slow to emerge and is transient. PMID- 11779390 TI - Clinical effectiveness and cost effectiveness of zanamivir (Relenza): translating the evidence into clinical practice, a National Institute for Clinical Excellence view. AB - The UK National Institute for Clinical Excellence (NICE) is charged with the duty of providing informed guidance on clinical practice (clinical effectiveness and cost effectiveness) to patients and health professionals. The Appraisal Committee through its process of review of evidence advises NICE on the clinical effectiveness and cost effectiveness of new and existing technologies and their appropriate use within the National Health Service in England and Wales. The appraisal process takes into account both published and unpublished evidence as well as input from professional and patient and carer groups when coming to its decisions. The appraisal of a new technology often has to bridge the gap between the evidence required for licensing purposes and that needed to provide pragmatic advice to practising clinicians. The appraisal of zanamivir (Relenza) is an excellent working example of this difficult and important process. PMID- 11779391 TI - RWJ-270201 (BCX-1812): a novel neuraminidase inhibitor for influenza. AB - The influenza virus neuraminidase (NA) is important in the pathogenesis of infection and, thus, is an attractive target for agents used in the treatment and prophylaxis of influenza. This article describes preclinical and early clinical data related to RWJ-270201 (BCX-1812), a novel, orally active NA inhibitor that was rationally designed for having potent and selective activity against influenza A and B viruses. RWJ-270201 is a unique NA inhibitor with a cyclopentane ring structure and high selectivity for the influenza NA. RWJ-270201 has efficacy comparable to or better than earlier NA inhibitors against a wide range of influenza A and B isolates, including recently emerged and avian strains, both in vitro and in a lethal murine model of influenza. Based on the high selectivity and efficacy of RWJ-270201 against both type A and B influenza strains in preclinical studies as well as murine pharmacodynamic studies supporting the potential for once-daily administration, clinical trials were initiated in order to determine the tolerability and antiviral activity of RWJ 270201 in humans. To date, clinical studies have indicated that RWJ-270201 is well tolerated and has antiviral activity in human experimental influenza models when administered orally once daily. PMID- 11779392 TI - A flu optical immunoassay (ThermoBioStar's FLU OIA): a diagnostic tool for improved influenza management. AB - ThermoBioStar's and Biota's flu optical immunoassay (FLU OIA) is a rapid test designed to diagnose influenza A and B infection using a variety of specimen types. The assay uses highly sensitive thin-film detection methods, coupled with specific monoclonal antibodies to the nucleoprotein. The test is simple to perform, requires no instrumentation and is intended to provide a result within 15 min of test initiation in the 'point-of-care' environment. In initial clinical studies, the assay was demonstrated to be equivalent to culture in identifying infected individuals. Subsequent independent studies using a variety of sample types have demonstrated sensitivity ranging from 48 to 100% and specificities ranging from 93 to 97%. In addition to detecting human strains, this assay has been demonstrated to be capable of detecting a variety of avian and non-human mammalian influenza viruses. The FLU OIA test has been used in large-scale surveillance schemes intended to provide rapid epidemiological data during normal influenza seasons and has demonstrated the potential for fulfilling a similar role for multispecies surveillance in, for example, conditions that offer challenges for conventional virus isolation methods. Conceivably, such use should facilitate the timely recognition of influenza outbreaks and prioritization of positive specimens for more conventional, laboratory characterization, leading to improved interpandemic surveillance and rapid reaction in the face of the next pandemic. PMID- 11779393 TI - Rapid diagnostics: the detection of neuraminidase activity as a technology for high-specificity targets. AB - The accurate detection of influenza by clinical symptoms is challenging since multiple pathogenic viruses and bacteria mimic similar symptoms in a patient. With new and more effective influenza therapeutics available, there is a growing need for highly accurate and rapid diagnosis of influenza, particularly when the window of opportunity for proper treatment is measured in hours. A parallel technology, which is also used in the treatment of influenza, was developed for the rapid diagnosis of influenza by exploiting the enzymatic activity of influenza neuraminidase. This technology, which is called Pathozyme, offers the high specificity inherent from the conservation of the neuraminidase active site. The ZstatFlu test uses a small molecule derivative of sialic acid chemically coupled to a reporter group together with simple point-of-care reagents for directly detecting influenza from a patient specimen with high specificity. A second-generation platform technology using this neuraminidase detection system coupled with a more sensitive chemiluminescent reporter has been developed and formatted for reading on high-speed instant film. This modification resulted in a platform technology many-fold more sensitive than the former while maintaining its inherent high specificity. Preliminary data from a prototype tested during the mild 2000-2001 influenza season demonstrated that an optimized chemiluminescent test system could approach the accuracy of 14 day viral culture in a convenient 10-20 min test. This platform technology is currently being explored for the rapid detection of other pathogenic organisms where sensitivity, specificity and speed are essential in a point-of-care setting. PMID- 11779394 TI - Influenza diagnosis and treatment: a view from clinical practice. AB - Influenza is a descriptive term for respiratory epidemic disease presenting with cough and fever. Influenza viruses are probably the most important of the pathogens that cause this condition. Clinical influenza occurs almost every winter in England and Wales and the outbreaks last 8-10 weeks. In recent years, influenza B virus outbreaks have occurred in January and February, whereas influenza H3N2 virus outbreaks have generally started long before Christmas. Influenza H3N2 virus outbreaks pressurize health service resources in winter more than influenza B viruses, that do not have the same impact in elderly people. Infections with influenza H1N1 viruses are also usually less severe in their impact than those with influenza H3N2 viruses, but, unlike influenza B viruses, influenza H1N1 viruses have a pandemic potential along with influenza H3N2 viruses. A diagnosis of respiratory infection in primary care is based on the presenting symptoms set within the context of the current pattern of consultations of patients with similar illness. Measurement of temperature, inspection of the throat and examination of the chest or ears add a little to the diagnostic process, but in general these procedures do not help in identifying the organism. However, if it is known that influenza viruses are circulating in the community, the probability of influenza as the cause is greatly increased, as was shown in clinical trials of neuraminidase antivirals. Maximum confusion occurs when respiratory syncytial virus (RSV) and influenza cocirculate. Although RSV infection can occur throughout the winter in young children, it assumes more of an epidemic character just before Christmas in children and possibly in adults just after. During seven of the last 20 winters, influenza has been prevalent around Christmas/New Year. In routine virological surveillance of influenza-like illness in the community during the winters of 1997, 1998 and 1999, ca. 30% of swab specimens yielded influenza viruses and 20% RSV. Given the limitations for routine surveillance, including variations in the interval between illness onset and specimen capture, the quality of swab, delays in transport, the growth properties of virus culture methods, etc., these figures probably underestimate the impact of both viruses in the community. The impact of influenza is considered against the background of total respiratory infections presenting to general practitioners over the last 10 years and some comparisons are made with the 1969 pandemic experience. Lessons relevant to pandemic planning are drawn. Current options for investigation and treatment are compared with those available in 1969. These include near-patient tests for assisting with diagnosis, widespread use of vaccination as a preventive in patients at increased risk, the availability of amantadine and the newer neuraminidase inhibitor antivirals and changes in the delivery of health care. Major advances in the understanding of influenza and improvements in investigation and treatment have taken place over the last 30 years. However, there are many obstacles before these can be translated into effective management of influenza sufferers and control of major epidemics. PMID- 11779395 TI - Zanamivir: an alternative translation. AB - This paper offers an alternative view to that given elsewhere regarding the value of zanamivir as an agent for treating patients who develop influenza symptoms. The position taken here has developed as a result of an analysis of the data that was undertaken by the journal Drug and Therapeutics Bulletin. PMID- 11779396 TI - Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children. AB - Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults. PMID- 11779397 TI - Developing vaccines against pandemic influenza. AB - Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID- 11779398 TI - Soluble recombinant influenza vaccines. AB - Soluble, recombinant forms of influenza A virus haemagglutinin and neuraminidase have been produced in cells of lower eukaryotes, and shown in a mouse model to induce complete protective immunity against a lethal virus challenge. Soluble neuraminidase, produced in a baculovirus system, consisted of tetramers, dimers and monomers. Only the tetramers were enzymatically active. The immunogenicity decreased very considerably in the order tetra > di > mono. Therefore, we fused the head part of the neuraminidase gene to a tetramerizing leucine zipper sequence; the resulting product was enzymatically active, tetrameric neuraminidase. The protective immunity induced by this engineered neuraminidase, however, remained fairly strain-specific. A third influenza A virus protein, the M2 protein, has only 23 amino acids exposed on the outer membrane surface. This extracellular part, M2e, has been remarkably conserved in all human influenza A strains since 1933. By fusing the M2e sequence to hepatitis B virus core protein, we could obtain highly immunogenic particles that induced complete, strain independent, long-lasting protection in mice against a lethal viral challenge. Native M2 is a tetrameric protein and this conformation of the M2e part can also be mimicked by fusing this sequence to a tetramerizing leucine zipper. The potential of the resulting protein as a vaccine candidate remains to be evaluated. PMID- 11779399 TI - Plasmid-only rescue of influenza A virus vaccine candidates. AB - The potential threat of another influenza virus pandemic stimulates discussion on how to prepare for such an event. The most reasonable prophylactic approach appears to be the use of effective vaccines. Since influenza and other negative stranded RNA viruses are amenable to genetic manipulation using transfection by plasmids, it is possible to outline new reverse genetics-based approaches for vaccination against influenza viruses. We suggest three approaches. First, we use a plasmid-only rescue system that allows the rapid generation of high-yield recombinant vaccine strains. Second, we propose developing second-generation live influenza virus vaccines by constructing an attenuated master strain with deletions in the NS1 protein, which acts as an interferon antagonist. Third, we suggest the use of Newcastle disease virus recombinants expressing influenza virus haemagglutinin proteins of pandemic (epizootic) strains as novel vaccine vectors for use in animals and possibly humans. PMID- 11779400 TI - Human immunodeficiency virus type 1-mediated syncytium formation is compatible with adenovirus replication and facilitates efficient dispersion of viral gene products and de novo-synthesized virus particles. AB - Conditionally replicative adenovirus (CRAd) vectors are designed for specific oncolytic replication in tumor tissues with concomitant sparing of normal cells. As such, CRAds offer an unprecedented level of anticancer potential for malignancies that have been refractory to previous cancer gene therapy interventions. CRAd efficacy may, however, be compromised by inefficient dispersion of the replicating vector within the tumor tissue. To address this issue, we evaluated the utility of a fusogenic membrane glycoprotein (FMG), which induces the fusion of neighboring cellular membranes to form multinucleated syncytia. We hypothesized that the FMG-mediated syncytia would facilitate dispersion of the adenovirus (Ad) gene products and viral progeny. To test this, human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, which induce syncytia in the presence of CD4+ target cells, were expressed by an Ad (Ad5HIVenv) in permissive (CD4-positive) and nonpermissive (CD4-negative) cell lines. After validating this Ad-FMG model, the efficiency of Ad replication in the presence or absence of syncytia was evaluated. The results demonstrated that syncytium formation was compatible with Ad replication and dramatically increased the dispersion of virus gene products within the cytoplasm of the syncytia as well as viral particles in the nuclei of the syncytial mass. Moreover, progeny virions were released more efficiently from syncytia compared with nonsyncytial cells. These data demonstrate the utility of FMGs as a dispersion agent and suggest that FMGs can improve the efficacy of CRAd gene therapy. PMID- 11779401 TI - Comparison of the effect of adenoviral delivery of three superoxide dismutase genes against hepatic ischemia-reperfusion injury. AB - The purpose of this study was to investigate the effectiveness of superoxide dismutase (SOD) overexpression in an acute model of hepatic oxidative stress. Oxidative stress was established using a warm ischemia-reperfusion model, where nearly 70% of the liver was made hypoxic by clamping the hepatic artery and a branch of the portal vein for 1 hr followed by restoration of blood flow. Animals were infected i.v. with 1 x 10(9) plaque-forming units (PFU) of adenovirus containing the transgene for cytosolic Cu/Zn-SOD (Ad.SOD1), mitochondrial Mn-SOD (Ad.SOD2), extracellular Cu/Zn-SOD (Ad.SOD3), or the bacterial reporter gene for beta-galactosidase (Ad.lacZ) 3 days prior to experiments. Ad.SOD1 and Ad.SOD2 caused a three-fold increase in SOD expression and activity in liver compared to Ad.lacZ-treated control animals. Intravenous administration of Ad.SOD3 increased SOD activity slightly in serum but not in liver. Increases in serum transaminases and pathology due to ischemia-reperfusion were blunted by Ad.SOD1 and Ad.SOD2; however, extracellular SOD had no significant effect. Moreover, lipid-derived free radical adducts (a(N) = 15.65 G and a(H)(beta) = 2.78 G) were increased by ischemia-reperfusion. This effect was blunted by about 60% in Ad.SOD1- and Ad.SOD2-infected animals, but was unaffected by Ad.SOD3. However, when high doses of Ad.SOD3 (3 x 10(10) PFU) were administered. serum SOD activity was elevated three-fold and was protective against hepatic ischemia-reperfusion injury under these conditions. These data demonstrate that adenoviral delivery of superoxide dismutase can effectively reduce hepatic oxidative stress. PMID- 11779402 TI - In vivo gene delivery via portal vein and bile duct to individual lobes of the rat liver using a polylysine-based nonviral DNA vector in combination with chloroquine. AB - The objective of this study was to evaluate a bifunctional synthetic peptide as a DNA vector for regional gene delivery to the rat liver by the portal vein and bile duct routes. The 31-amino-acid peptide (polylysine-molossin) comprises an amino-terminal chain of 16 lysines for electrostatic binding of DNA, and the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus. Initial in vitro evaluation demonstrated that polylysine-molossin/DNA complexes were much smaller (approximately 50-100nm versus 500-1300nm), more positively charged, and more stable in isotonic dextrose in comparisons with salt-containing solutions. However, polylysine-molossin/DNA complexes in any solution other than complete culture medium were ineffective for gene delivery in vitro. Vector localization studies demonstrated that both the portal vein and bile duct routes provided excellent access of polylysine molossin/DNA complexes to the liver. However, complexes delivered by the portal vein were rapidly lost (<15 min) following re-establishment of the portal circulation, whereas complexes delivered by the bile duct persisted much longer. Polylysine-molossin/DNA complexes in various isotonic solutions were delivered to the right lateral lobes either by perfusion through a branch of the portal vein or by infusion into appropriate branches of the bile duct. Two or three hours before gene delivery, rats were given a single injection of chloroquine. We report that the polylysine-molossin vector is much more effective (>10-fold) when delivered by the bile duct route with all isotonic solutions evaluated, and that polylysine-molossin/DNA complexes in isotonic dextrose are much more effective (>10-fold) than complexes in salt-containing solutions. PMID- 11779403 TI - Enhancement of Fas ligand-induced inhibition of neointimal formation in rabbit femoral and iliac arteries by coexpression of p35. AB - Adenovirus-mediated gene transfer of Fas ligand (FasL) inhibits neointimal formation in balloon-injured rat carotid arteries. Vascular smooth muscle (VSM) cells coexpressing murine FasL and p35, a baculovirus gene that inhibits caspase activity, are not susceptible to FasL-mediated apoptosis in vitro but are capable of inducing apoptosis of VSM cells that do not express p35. We reasoned that coexpression of p35 in FasL-transduced VSM cells in vivo would promote their survival, enhance FasL-induced apoptosis of adjacent VSM cells, and thereby facilitate a greater inhibition of neointimal formation. In balloon-injured rabbit femoral arteries, either Ad2/FasL/p35 or Ad2/FasL was infused into the injured site and withdrawn 20 min later. Both vectors induced a dose-dependent reduction (p < 0.05) of the neointima-to-media ratio when assessed 14 days later. However, Ad2/FasL/p35 exhibited a significantly greater inhibition of neointimal formation than Ad2/FasL. In a more clinically relevant model of restenosis, rabbit iliac arteries were injured with an angioplasty catheter under fluoroscopic guidance. Adenoviral vectors were delivered locally to the injured site over a period of 2 min, using a porous infusion balloon catheter. Twenty eight days after gene transfer angiographic and histologic assessments indicated a significant (p < 0.05) inhibition of iliac artery lumen stenosis and neointimal formation by Ad2/FasL/p35 (5 x 10(11) particles per artery). The extent of inhibition was comparable to that achieved with Ad2/TK, an adenoviral vector encoding thymidine kinase (5 x 10(11) particles per artery) and coadministration of ganciclovir for 7 days. These data suggest that coexpression of p35 in FasL transduced VSM cells is more potent at inhibiting neointimal formation and as such represents an improved gene therapy approach for restenosis. PMID- 11779404 TI - Lentiviral vector-mediated tyrosinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma. AB - Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a vital role in primary immune responses. Introducing genes into DCs will allow constitutive expression of the encoded proteins and thus prolong the presentation of the antigens derived therefrom. In addition, multiple and unidentified epitopes encoded by the entire tumor-associated antigen (TAA) gene may enhance T cell activation. This study demonstrated that an HIV-1-based lentiviral vector conferred efficient gene transfer to DCs. The transgene, murine tyrosinase-related protein 2 (mTRP-2), encodes a clinically relevant melanoma associated antigen (MAA), which has been found to be a tumor rejection antigen for B16 melanoma. The transfer and proper processing of mTRP-2 in DCs, in terms of RNA transcription activity and protein expression, were verified by RT-PCR and specific antibody, respectively. Administration of mTRP-2 gene-modified DCs (DC HR' CmT2) to C57BL/6 mice evoked strong protection against tumor challenge, for which the presence of CD4+ and CD8+ cells during both the priming and challenge phase was essential. In a therapy model, our results showed that four of seven mice with preestablished tumor remained tumor free for 80 days after therapeutic vaccination. Given the results shown in this study, mTRP-2 gene transfer to DCs provides a potential therapeutic strategy for the management of melanoma, especially in the early stage of the disease. PMID- 11779405 TI - Evaluation of salivary gland acinar and ductal cell-specific promoters in vivo with recombinant adenoviral vectors. AB - Adenoviral vectors efficiently deliver exogenous genes to salivary glands. There are two general epithelial cell types, with very different functions, in salivary glands--acinar and ductal. To determine if gene expression can be restricted in vivo to either general cell type using a relatively cell/tissue-specific promoter in conjunction with adenovirus-mediated gene transfer, we tested the human amylase and kallikrein promoters. For initial studies the sensitive reporter gene luciferase was used in two adenoviral constructs. The adenovirus AdAMY-luc contains the human salivary gland amylase promoter (-1003 to +2)(AMY1C) and AdKALL-luc contains the human tissue kallikein promoter (-315 to -1)(KLK1). The adenovirus AdKALL-hAQP1 was also used to test a therapeutic gene, human aquaporin 1 (hAQP1), potentially of importance in treating surviving ductal cells in irradiation-damaged glands. Luciferase expression after AdAMY-luc delivery in vivo directly to the parotid, submandibular, and sublingual glands, as well as to the lungs, and intravenously via the femoral vein, was restricted to the three salivary glands and the pancreas. AdKALL-luc delivery via the same routes resulted in a more general distribution of luciferase expression, although greatest luciferase activity was seen in salivary glands and lung. Luciferase activity after AdAMY-luc delivery was proportionally greater (approximately 14 fold) in acinar cells, whereas luciferase activity after AdKALL-luc delivery was proportionally greater (approximately 9-fold) in ductal cells. The expression of hAQP1 after AdKALL-hAQP1 gene transfer was mainly observed in ductal cells in vivo. AdKALL-hAQP1 was as useful as AdCMV-hAQP1 in increasing salivary flow rates of irradiated rats. This study demonstrates that adenoviral vectors containing the relatively cell/tissue-specific AMY1C or KLK1 promoters may be useful for targeting therapeutic gene expression in salivary glands. PMID- 11779406 TI - Connexin 26 gene therapy of human bladder cancer: induction of growth suppression, apoptosis, and synergy with Cisplatin. AB - The connexin 26 (Cx26) gene encodes a protein involved in gap junctional intercellular communication and is a putative tumor suppressor. We constructed a Cx26 adenovirus vector (Ad-Cx26) and used it to infect human bladder cancer cell lines UM-UC-3, UM-UC-6, UM-UC-14, and T24. Infection with Ad-Cx26 suppressed the growth of these cell lines in vitro and prevented tumor formation in vivo. Cell cycle accumulation or arrest at the G(1) phase was noted in UM-UC-3 cells and at the G(2)/M phase in UM-UC-6, UM-UC-14, and T24 cells. Apoptosis was noted in UM UC-3, UM-UC-6, and UM-UC-14 cells both in vitro and in vivo. These effects were not seen with control adenovirus (Ad-CTR) or mock infection. Ad-Cx26 did not significantly alter the growth of the immortalized normal human bladder cell line SV-HUC. Direct injection of Ad-Cx26 into established UM-UC-3 and UM-UC-14 tumors in nude mice resulted in Cx26 expression, apoptosis, and significantly decreased growth compared with Ad-CTR treated tumors. Delayed resumption of tumor growth was associated with loss of Cx26 expression. Combination therapy with Ad-Cx26 and cisplatin resulted in decreased growth in vitro compared with either agent alone. We explored combination therapy with Ad-Cx26 and cisplatin to improve the in vivo efficacy of Cx26 gene therapy. In vivo therapy with Ad-Cx26 and cisplatin resulted in long-term suppression of tumor growth. These data demonstrate that combining gene and chemotherapy can result in dramatic synergy in vivo. PMID- 11779407 TI - Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies. AB - Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy. PMID- 11779408 TI - Human gene marker/therapy clinical protocols (complete updated listing). PMID- 11779411 TI - Assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee. PMID- 11779412 TI - Safety of local delivery of low- and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of morbid conditions. AB - To help define the safety profile of the use of adenovirus (Ad) gene transfer vectors in humans, this report summarizes our experience since April 1993 of the local administration of E1(-)/E3(-) Ad vectors to humans using low (<10(9) particle units) or intermediate (10(9)-10(11) particle units) doses. Included in the study are 90 individuals and 12 controls, with diverse comorbid conditions, including cystic fibrosis, colon cancer metastatic to liver, severe coronary artery disease, and peripheral vascular disease, as well as normals. These individuals received 140 different administrations of vector, with up to seven administrations to a single individual. The vectors used include three different transgenes (human cystic fibrosis transmembrane conductance regulator cDNA, E. coli cytosine deaminase gene, and the human vascular endothelial growth factor 121 cDNA) administered by six different routes (nasal epithelium, bronchial epithelium, percutaneous to solid tumor, intradermal, epicardial injection of the myocardium, and skeletal muscle). The total population was followed for 130.4 patient-years. The study assesses adverse events, common laboratory tests, and long-term follow-up, including incidence of death or development of malignancy. The total group incidence of major adverse events linked to an Ad vector was 0.7%. There were no deaths attributable to the Ad vectors per se, and the incidence of malignancy was within that expected for the population. Overall, the observations are consistent with the concept that local administration of low and intermediate doses of Ad vectors appears to be well tolerated. PMID- 11779413 TI - Analysis of risk factors for local delivery of low- and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of comorbid conditions. AB - In this study we analyze the adverse events and abnormal laboratory parameters following local administration of low (<10(9) particle units) and intermediate (10(9)-10(11) particle units) single and repetitive doses (140 total) of E1(-)E3( ) adenovirus (Ad) gene transfer vectors administered to the respiratory epithelium, solid tumors, skin, myocardium, and skeletal muscle in eight gene transfer trials since April 1993. In the accompanying paper by Harvey et al., (Hum. Gene Ther. 2002; 13:15-63), we conclude that for the total group, no deaths were attributable to the Ad vectors per se, and the incidence of major adverse events likely caused by an Ad vector was 0.7%. The present study analyzes the trials as a group to evaluate risk factors for the adverse events, abnormal values among laboratory parameters, and known deaths. Ten putative risk factors were assessed, including "patient-related" (age, sex, comorbid index and pretherapy anti-Ad antibodies), "vector-related" (dose, route, transgene, and number of vector administrations), and "trial-related" (trial in which the individual was enrolled, and whether surgery was part of the trial). While assessment of each factor individually suggested several possible associations with adverse events, abnormal laboratory parameters, or deaths, multivariate analysis identified only age, comorbid index, and surgery (comorbid index for death; age and surgery for non-death adverse events) as variables significantly associated with increased risk for a major (severity scale 3-4 of 4) adverse event for individuals enrolled in these gene transfer trials. Importantly, multivariate analysis suggested that vector-related parameters, including dose, route, transgene, or number of vector administrations at the doses and routes evaluated in these studies, do not appear to be significant risk factors for a major adverse event. With the caveat that these are phase I, uncontrolled trials, we conclude that (1) there is no definitive risk factor that will clearly predict a major adverse outcome resulting from local administration of low and intermediate doses of Ad gene transfer vectors; and (2) major adverse events in these gene transfer trials are associated primarily with the study population and/or trial procedures, not the Ad vectors themselves. This assessment is consistent with the concept that local administration of low and intermediate doses of Ad gene transfer vectors appears to be well tolerated. PMID- 11779414 TI - Subcutaneous Administration of a Replication-Competent Adenovirus Expressing HSV tk to Cotton Rats: Dissemination, Persistence, Shedding, and Pathogenicity. AB - Since human adenoviruses replicate only in human cells, toxicology studies with adenoviral vectors are hampered by the lack of a permissive nonhuman host. Before a replication-competent adenoviral vector expressing HSV-tk (Ad.OW34) can be used in clinical studies for intratumoral injections in patients with cutaneous lesions of head and neck cancer or intralesional injection for in situ vaccination strategy in advanced metastatic melanoma patients, risks have to be estimated in animal studies. In an attempt to assess potential toxicology, dissemination, persistence and shedding, we injected Ad.OW34 subcutaneously into cotton rats. (Sigmodon hispidus), which are considered a semi-permissive host for human adenoviruses. The animals underwent one or two subcutaneous injection cycles with 2.3 x 10(12) viral particles/kg each or a single course with 6.9 x 10(13) viral particles/kg and were analyzed at defined time points for histopathological changes in the brain, heart, lungs, spleen, liver, kidneys, ovaries, and skin. Additionally, these tissues as well as urine, feces, mouth, and skin swabs were analyzed at multiple time points by real-time quantitative polymerase chain reaction for the presence of vector sequences. The only significant treatment-related histopathologic finding was dermatitis with mild acanthosis at the site of vector injection. All other tissues evaluated were within normal limits or showed changes that were most likely incidental or spontaneous in nature. Vector sequences were detected in the skin at the injection site and to a lesser extent in the liver, spleen, and lungs. In addition, small amounts of vector DNA were detected in the ovaries. The vector sequences were rapidly cleared and the absence of viral sequences in the excreta and swabs of the majority of animals suggest that there was no significant replication of the vector in this host. The administration of Ad.OW34 was also associated with mild hyperamylasemia, lymphocytosis, and granulocytosis; however, we did not observe any clinical signs of illness or death in the experimental animals over the course of the study. PMID- 11779415 TI - Toxicity of a first-generation adenoviral vector in rhesus macaques. AB - We constructed a first-generation adenovirus vector (AVC3FIX5) that we used to assess the rhesus macaque as a nonhuman primate model for preclinical testing of hemophilia B gene therapy vectors. Although we succeeded in our primary objective of demonstrating expression of human factor IX we encountered numerous toxic side effects that proved to be dose limiting. Following intravenous administration of AVC3FIX5 at doses of 3.4 x 10(11) vector particles/kg to 3.8 x 10(12) vector particles/kg, the animals in our study developed antibodies against human factor IX, and dose-dependent elevations of enzymes specific for liver, muscle, and lung injury. In addition, these animals showed dose-dependent prolongation of clotting times as well as acute, dose-dependent decreases in platelet counts and concomitant elevation of fibrinogen and von Willebrand factor. These abnormalities may be caused by the direct toxic effects of the adenovirus vector itself, or may result indirectly from the accompanying acute inflammatory response marked by elevations in IL-6, a key regulator of the acute inflammatory response. The rhesus macaque may be a useful animal model in which to evaluate mechanisms of adenovirus toxicities that have been encountered during clinical gene therapy trials. PMID- 11779416 TI - Adenoviral vectors do not induce, inhibit, or potentiate human platelet aggregation. AB - Adenoviruses are commonly used as vectors in human clinical gene therapy trials. High doses of intravenous adenovirus vectors have been associated with development of thrombocytopenia of undetermined origin. Viral internalization requires the presence cell surface integrins, alpha(v)beta(3) or alpha(v)beta(5), that can blind ligands with a arginine-glycine-aspartic acid (RGD) sequence. This sequence is found in the adenovirus penton base. Platelets express the alpha(v)beta(3) integrin and other integrins that bind the RGD sequence of ligands such as fibrinogen, laminin, vitronectin, and von Willebrand factor (vWF). Platelet aggregation is mediated, in part, by the binding of the RGD sequence of fibrinogen to a platelet surface integrin, glycoprotein IIb/IIIa (GP IIb/IIIa). We investigated whether adenovirus particles could interfere with or potentiate agonist-induced platelet aggregation. Incubation of platelet-rich plasma with adenovirus under stirred conditions did not promote spontaneous aggregation. The addition of physiological platelet agonists, ADP, collagen, or epinephrine, induced platelet aggregation. However, the presence of adenovirus in a wide range of concentrations did not inhibit or potentiate agonist-induced aggregation. These results suggest that the adenovirus-associated thrombocytopenia observed in vivo is independent of a direct effect of the virus on platelet aggregation. PMID- 11779417 TI - The release of inflammatory cytokines from human peripheral blood mononuclear cells in vitro following exposure to adenovirus variants and capsid. AB - Preclinical and clinical studies with adenoviral vectors have clearly illustrated the potential advantages of this gene transfer system. However, many studies have also demonstrated potent immune responses directed at both vector and transduced cells. We examined in vitro responses of human peripheral blood mononuclear cells (PBMC) to virus exposure as a model for this host response. PBMC were isolated from normal donors and incubated with wild-type adenovirus (Ad5), Ad5 variants deleted for segments of E1 and/or E3, and empty viral capsids. Proinflammatory cytokine release was monitored for 96 hr. Induction of TNF-alpha by intact virions was low although stimulation by empty capsid gave a significant and sustained response. Induction of IL-6, GM-CSF, and a panel alpha- and beta chemokines by intact virions was prominent, often approaching results obtained with 2.5 microg/ml of lipopolysaccharide (LPS). Responses were generally independent of virion genetic composition and were only partially blunted when UV inactivated virus was used. Dose-response data showed 100-fold increases in virion concentration produced a maximum 3-fold increase in cytokine release, suggesting saturation. Surprisingly, prominent stimulation occurred after addition of empty capsid, which typically provoked responses equivalent to those seen with LPS stimulation. We present arguments that cellular signal transduction mechanisms activated by binding of virions/capsids stimulate transcription of proinflammatory cytokine genes. PMID- 11779418 TI - Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. AB - The effects of intravenous administration of a first-generation adenoviral vector expressing beta-galactosidase were compared in two baboons receiving a high dose or lower dose of vector, 1.2 x 10(13) or 1.2 x 10(12) particles/kg, respectively. The high-dose baboon developed acute symptoms, decreased platelet counts, and increased liver enzymes, and became moribund at 48 hr after injection, while the lower-dose baboon developed no symptoms. Expression of the beta-galactosidase transgene was prominent in liver, spleen, and endothelium of the arterial vasculature in the high-dose baboon, but was much more limited and spared the endothelium in the lower-dose baboon. Injury to the vascular endothelium was the most prominent abnormality in the high-dose baboon. Extensive histological studies provide a detailed picture of the pathology associated with a lethal dose of first-generation adenoviral vector in a primate. PMID- 11779419 TI - Effect of blood collection technique in mice on clinical pathology parameters. AB - A study was conducted in normal healthy C57BL/6 mice to determine the effect of method of blood collection on clinical pathology parameters and to provide value ranges for these parameters. Males and females were used and were randomly assigned to treatment groups based upon phlebotomy method. The blood was collected using one of four methods: intracardiac (IC), a single attempt at collection from the caudal vena cava (VC), collection from the caudal vena cava with collection of any extravasated blood from the peritoneum (MC), or retroorbital phlebotomy (RO). Evaluation of blood and serum samples was conducted for a number of serum biochemistries including liver function tests and complete blood count with differentials and platelet counts. Female mice demonstrated higher values for red blood cell number, hemoglobin (p < 0.002), hematocrit, alkaline phosphatase, albumin, total protein, and creatinine. Males demonstrated higher values for platelet counts, specific white blood cell numbers (total, neutrophil, lymphocyte, and eosinophil counts), globulin, amylase, and the BUN/creatinine ratio. Overall, the VC method was associated with the least variation in both sexes and appeared slightly better than the IC method for the parameters evaluated. The largest difference between groups was noted for the transaminase levels. While alanine aminotransferase (ALT) values were similar between the IC and VC groups, aspartate aminotransferase (AST) values were associated with less variation for the VC method. Transaminase levels for the MC and RO groups were associated with relatively large ranges and variation. ALT results from the RO method, the only method amenable to repetitive sample collection used in this evaluation, indicate that this is an acceptable method. The results demonstrate the substantial impact that phlebotomy method has on the assay results and that the VC or IC methods provide the most consistent results. The ranges by collection method and sex provided here can be used to select the preferred method of collection when designing a study and for comparison of data obtained with reference ranges. The authors recommend establishment of normal ranges based upon methods employed within an investigator's laboratory. PMID- 11779421 TI - Measuring self-reported sunburn: challenges and recommendations. AB - Sunburn is a major preventable risk associated with the development of malignant melanoma and basal cell carcinoma. Thus, it is considered a key epidemiological concept to assess in prevention research and a core component of routine behavioural surveillance and program evaluation efforts. This review examined 38 English- language survey instruments and research reports published between 1990 and 1999 that used self-report data or parent-proxy reports of sunburn outcome. A qualitative review of the instruments and reports identified several methodological issues: the conceptual and operation definitions of sunburn; the recall period, and the use of self-reports and parent-proxy reports. As there was little consistency in definitional issues or recall periods across the studies, it is difficult to meaningfully compare their findings. Key issues that program evaluators and researchers should consider in determining the strengths and limitations of various definitions, measures and approaches are examined. Recommendations for measurement of sunburn and for further research are included. PMID- 11779420 TI - A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. AB - Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis that has been considered as a model for liver-directed gene therapy. Current treatment has failed to avert a high mortality or morbidity from hyperammonemic coma. Restoration of enzyme activity in the liver should suffice to normalize metabolism. An E1- and E4-deleted vector based on adenovirus type 5 and containing human OTC cDNA was infused into the right hepatic artery in adults with partial OTCD. Six cohorts of three or four subjects received 1/2 log increasing doses of vector from 2 x 10(9) to 6 x 10(11) particles/kg. This paper describes the experience in all but the last subject, who experienced lethal complications. Adverse effects included a flu-like episode and a transient rise in temperature, hepatic transaminases, thrombocytopenia, and hypophosphatemia. Humoral responses to the vector were seen in all research subjects and a proliferative cellular response to the vector developed in apparently naive subjects. In situ hybridization studies showed transgene expression in hepatocytes of 7 of 17 subjects. Three of 11 subjects with symptoms related to OTCD showed modest increases in urea cycle metabolic activity that were not statistically significant. The low levels of gene transfer detected in this trial suggest that at the doses tested, significant metabolic correction did not occur. PMID- 11779422 TI - Assessment of hand-arm vibration syndrome in a northern Ontario base metal mine. AB - The objective of this study was to determine the prevalence of hand-arm vibration syndrome (HAVS) in 617 workers at a base metal mine in northern Ontario. Workers who were employed at the mine between the years 1989 and 1994 and who continued to live within a 100 km radius of the mine were sent a self-reported questionnaire to identify individuals with possible vibration-induced symptoms in their upper extremities. Of the 162 workers who attended the medical examination, 50% were diagnosed with HAVS, 26% had other diagnoses with some workers having multiple afflictions e.g., both HAVS and carpal tunnel syndrome (CTS). No vibration-induced symptoms were reported in 35% of the workers who were clinically normal. The study was designed to educate, advise, and to make recommendations on the prevention of HAVS. Ongoing commitments to technological improvements, mandatory and regular rest periods, and continuing educational sessions on the syndrome should help to reduce the prevalence of this disease. PMID- 11779423 TI - Validity of the US Behavioral Risk Factor Surveillance System's health related quality of life survey tool in a group of older Canadians. AB - Investigators at the Centers for Disease Control and Prevention in the US have developed a brief survey tool to measure health-related quality of life (HRQOL 4). In order to support use of such tools in surveillance, it is important to assess their validity in different groups. Subjects were 926 non institutionalized men and women (age > or = 65 years) who completed a health exam and questionnaire. Results indicated that physical and mental health and physical activity limitation were each related to self-perceived health. Compared with subjects who reported excellent health, those with poor self-rated health reported a more than 17-fold increase in the number of unhealthy days in the previous 30. While responses to questions addressing psychosocial factors were most consistently associated with the HRQOL item relating to mental health, responses to health and health behaviour questions were more consistently associated with items related to physical health. This study demonstrated that the HRQOL-4 is not only accepted by older adults in a self-administered format, but also stands up to tests of its validity. PMID- 11779424 TI - Canadian Cancer Society Information Services: lessons learned about complementary medicine information needs. AB - The use of complementary and alternative medicine (CAM) in cancer patients is very common. However, currently valid and reliable information on CAM treatments for cancer is limited. The purpose of this study was to identify the information needs those who called the Canadian Cancer Society's Cancer Information Service (CIS) requesting information on CAM. CIS Information Specialists completed two page questionnaires for 109 callers who inquired about CAM therapies. Findings show that the majority of callers were women between the ages of 30 and 59, and that most of their questions concerned the safety and/or effectiveness of herbs and compounds like Essiac and 714X. Information Specialists generally utilized one or more of four resources upon receiving a CAM-related call. These resources, while mostly Canadian and reviewed by content experts, are not specific to the type of cancer and are no longer the most up- to-date. To address this issue we have included an appendix that outlines some current CAM resources and websites for cancer patients. PMID- 11779426 TI - Multi-organ protection during open heart surgery. AB - PURPOSE AND METHODS: Open-heart surgery with the use of cardiopulmonary bypass (CPB) is associated with an inflammatory cascade which contributes to the development of postoperative complications including multiple organ failure. To provide an update on the subject, we briefly review the recent English-language literature. RESULTS: During CPB, various factors have been recognized to induce a complex inflammatory response. Based on an enhanced understanding of the underlying mechanisms, therapeutic strategies have been developed to reduce this inflammatory reaction and its subsequent damaging effects. Off-pump coronary artery bypass grafting may result in less inflammatory injury as compared with the conventional maneuver, which can in turn, diminish the incidence of cardiac, renal, or neurological dysfunction. It is also clear that improving the biocompatibility of CPB materials can lead to a better patient recovery. Inasmuch as the pathophysiology involved appears to be multifactorial, it is unlikely that a single intervention could achieve the desired goal. Both pharmacologic strategies, such as steroid pretreatment, and modification of mechanical devices, such as the use of heparin-coated CPB circuits, could have important clinical implications. The balance pro- and anti-inflammatory responses may be crucial in limiting the extent of inflammatory injury. CONCLUSIONS: To date, the concept of organ protection should no longer be limited to the individual organ. Instead, investigations must be extended to focus on a systemic level. PMID- 11779427 TI - Cationic antimicrobial protein of Mr 37 kDa: a multifunctional inflammatory protein. AB - PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. DATA SOURCES: Endothelial cells used in this study were obtained from human lung microvessels and rat aorta. The latter was a kind gift of Dr. Paula Grammas. The mono-mac 6 cell line used in this study was the generous gift of Dr. H.W. Loms Ziegler-Heitbrock. STUDY SELECTION AND DATA EXTRACTION: Endothelial cell proteins kinase C activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone. Endothelial cell migration was determined using Costar Transwell apparatus. Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS. RESULTS: We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endothelial cell protein kinase C in a dose- and time dependent fashion. Importantly CAP37 increased the adhesive properties of the endothelium for monocytes. CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time-dependent manner. In addition, CAP37 promoted endothelial cell migration. Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory mediators such as lipopolysaccharide. Unstimulated endothelial cells did not constitutively express CAP37. The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-derived CAP37. CONCLUSIONS: Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues. PMID- 11779428 TI - Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alpha IIb beta 3 activation in a Fc receptor-independent fashion. AB - OBJECTIVES: To characterize the activation of platelet integrin alpha IIb beta 3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action. METHODS: Using 125I-labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured. RESULTS: HI117 and SJ9A4 (10 micrograms/ml and 20 micrograms/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alpha IIb beta 3. Further study indicated that HI117 and SJ9A4 induced integrin alpha IIb beta 3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alpha IIb beta 3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI2. CONCLUSIONS: Anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alpha IIb beta 3 activation independent of Fc-receptors. Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways. PMID- 11779429 TI - Arsenic trioxide induces multiple myeloma cell apoptosis via disruption of mitochondrial transmembrane potentials and activation of caspase-3. AB - OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (delta psi m) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. RESULTS: Zero point one to 0.5 mumol/L As2O3 inhibited cell proliferation and 2.0 mumol/L As2O3 induced cell apoptosis, while 1.0 mumol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (delta psi m) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced delta psi m collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. CONCLUSION: As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction. PMID- 11779430 TI - A bicistronic retroviral vector to introduce drug resistance genes into human umbilical cord blood CD34+ cells to improve combination chemotherapy tolerance. AB - OBJECTIVE: To study whether human umbilical cord blood CD34+ cells transduced with human aldehyde dehydrogenase class-1 (ALDH-1) and multidrug resistance gene (MDR1) have increases resistance to 4-Hydroperoxycyclo-phosphamide (4-HC) and P glycoprotein effluxed drugs. METHODS: A bicistronic retroviral vector G1Na-ALDH1 IRES-MDR1 was constructed and used to transfect the packaging cell lines GP + E86 and PA317 by LipofectAMINE method, using the medium containing VCR and 4-HC agents for cloning selection and ping-ponging supernatant infection between the ecotropic producer clone and the amphotropic producer clone, we obtained high titer amphotropic PA317 producing cells with high titers up to 5.6 x 10(5) CFU/ml. Cord blood CD34+ cells were transfected repeatedly with supernatant of retrovirus containing human ALDH-1 and MDR1cDNA under the stimulation of hemopoietic growth factors. RESULTS: Bicistronic retroviral vector construction was verified by restriction endonuclease analysis. Polymerase chain reaction (PCR), reverse transcription (RT)-PCR, Southern blot, Northern blot, fluorescenceactivated cell sorting (FACS) method and 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) analyses showed that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgenes recipient cells confered 4-fold stronger resistance to 4-HC and 5.5 to 7.2-fold P-glycoprotein effluxed drug than untransduced cells. CONCLUSION: The bicistronic retroviral vector-mediated transfer of two different types of drug resistance genes into human cord blood CD34+ cells and co-expression provided an experimental foundation for improving combination chemotherapy tolerance in tumor clinical trial. PMID- 11779431 TI - Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells. AB - OBJECTIVE: To study the effect of all-trans retinoic acid (ATRA) and arsenic troxide (As2O3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: PCA from freshly isolated APL blasts from APL patients treated with ATRA or As2O3 was detected using a one-stage clotting assay. TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitive (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV-PML RARa treated with or without ATRA or As2O3, were also examined. RESULTS: Both ATRA and As2O3 can down-regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time-dependent manner. The TF antigen level in PML-RARa + U937 cells was significantly higher than that in U937 cells infected with retrovirus vector. Both ATRA and As2O3 can also down regulate the TF antigen in U937 cells transfected with or without PML-RARa. CONCLUSION: Tissue factor expression and PCA in APL cells may be down-regulated by ATRA and As2O3. By down-regulating TF expression, As2O3 might also be used to improve the DIC-related hemorrhage in APL. Our data indicate that elevated TF antigen in PML-RARa + U937 may be related to the fusion protein PML-RARa. The down-regulating effect of ATRA and As2O3 on TF expression in U937 cells might not involve this fusion protein. PMID- 11779432 TI - Identification of metastasis associated gene G3BP by differential display in human cancer cell sublines with different metastatic potentials G3BP as highly expressed in non-metastatic. AB - OBJECTIVE: To investigate genes involved in cancer metastasis, mRNA differential display was used to compare the levels of gene expression in two cell sublines derived from human giant cell carcinoma of lung (PG) which had different metastatic potentials. METHODS: Using in vivo tumorigenicity and a spontaneous metastasis assay in nude mice, two sublines (BE1, LH7) from human giant cell carcinoma of lung (PG) with different metastatic potentials were isolated and characterized. mRNA differential display was used to compare the levels of gene expression between them and the obtained results were confirmed by Northern hybridization. RESULTS: One differentially expressed band was nearly identical (99% homology) to Ras-GTPase-Activating protein SH3 domain binding protein (G3BP). G3BP displayed a strong expression in LH7 (non-metastatic in recipient nude mice) and a very weak expression in BE1 (100% metastatic frequency). The same different expression level of G3BP was detected in Northern hybridization with another panel of cell sublines with different metastatic potentials (established in our lab) derived from human prostate carcinoma cell line PC-3M. CONCLUSION: Our results indicate that G3BP was implicated in cancer metastasis because of its differential expressions in the two panels of cell sublines with different metastatic potentials. PMID- 11779433 TI - Relationship between tumor suppressor gene p53 and tumors of adipose tissue. AB - OBJECTIVE: To investigate the relationship between p53 gene and tumors of adipose tissue at the level of protein and gene. METHODS: Immunohistochemical LSAB, PCR SSCP and DNA sequencing were used in 82 cases. RESULTS: p53 protein is expressed only in liposarcomas, in which the positive staining rate was 48.08% (25/52). In different subtypes of liposarcomas, the positive staining rate in well differentiated liposarcomas was 30.00% (9/30), which is much lower than that of the poorly differentiated liposarcomas (P < 0.005). Abnormality in the single stranded DNA pattern was determined in 2 samples (pleomophic liposarcomas) by PCR SSCP analysis. Missense mutations in exon 8 codon 268 of p53 gene (AAC-->ATC) were detected by DNA sequencing. Another heterozygotic cosense mutation may exist at exon 6 codon 221 of p53 gene (GAG-->GAA). CONCLUSIONS: The data suggest that the p53 protein has a relationship with development, differentiation and malignancy of liposarcoma. Detecting the level of p53 protein expression may be valuable in evaluating the level of differentiation and malignancy of liposarcoma. There appear point mutation on exon 8, 6 of p53 gene. PMID- 11779434 TI - Clinicopathologic study of mucosa-associated lymphoid tissue lymphoma of the salivary gland. AB - OBJECTIVE: To study the histopathologic features and pathogenesis of mucosa associated lymphoid tissue lymphoma (MALT-oma) of salivary glands. METHODS: Clinical data, paraffin-embedded sections, immunohistochemical slides (SP method) and electron microscopic features of surgical specimens of 32 cases of salivary gland MALT-oma were studied. RESULTS: The patients were 27 males and 5 females, with a mean age of 54.76 years. The lesions were located in the parotid area in 17 cases, and in the submandibular gland in the remaining 15 cases. Much of the MALT-oma was replaced by infiltration of a great amount of centrocyte-like cells (CCL) as background and occasional large cells (centroblast- or immunoblast like). In MALT-omas "lymphoepithelial lesions" were present. Immunohistochemically, CD20 expression was found to be positive and CD45RO expression was negative in all MALT-omas. CONCLUSION: Most of the MALT-omas are low grade malignant tumors and have a "homing back" phenomenon. The cases were managed by surgery and chemotherapy. In a few MALT-omas which turned into high grade malignant tumors, the prognosis was poor. Acquired MALT may develop as a reaction to autoimmune disease and infection. Hyper-immune reaction and MALT hyperplasia under stimulation may result in myoepithelial sialadenitis and lead to MALT-oma of the salivary gland. PMID- 11779435 TI - Expression of exon 13 from the Ki-67 gene in human cells and tissues by digoxigenin-labelled mRNA in situ hybridization. AB - OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study the Ki-67 gene transcription and translation in various human cells and tissues. HeLa cells and fresh colon cancer cells, tonsil, normal pancreas and pancreatic cancer tissues were used in this study. A 435 bp cDNA fragment located in exon 13 of the Ki-67 antigen gene was amplified by polymerase chain reaction (PCR). Digoxigenin labelled antisense and sense RNA probes were prepared for detecting Ki-67 mRNA, combined with MIB-1 immunohistochemistry. RESULTS: Successful localization of Ki 67 mRNA in human HeLa cells, colon cancer cells, tissues specimen of the tonsil and pancreatic cancer tissue sections was accomplished by digoxigenin-labelling in situ hybridization technique. ISH to colon cancer cells and pancreatic cancer tissue slides showed that much stronger cytoplasm and perinuclear mRNA signals of the Ki-67 gene were present in malignant cells than in normal cells, which was in accordance with MIB-1 nuclear protein signals. CONCLUSIONS: A sensitive and practical in situ hybridization method for the analysis of Ki-67 antigen mRNA in human cell and tissue was developed. Abnormal transcription of exon 13 of Ki-67 gene might be responsible for malignant cell proliferation in colon and pancreatic cancer. PMID- 11779436 TI - Laryngeal and hypopharyngeal carcinoma: comparison of helical CT multiplanar reformation, three-dimensional reconstruction and virtual laryngoscopy. AB - OBJECTIVE: To evaluate the clinical application of helical CT multiplanar reformation (MPR) three-dimensional reconstruction (3D) and virtual laryngoscopy (CTVL) in laryngeal and hypopharyngeal carcinoma. METHODS: Axial helical CT scans were performed in 22 patients with laryngeal or hypopharyngeal carcinoma, along with MPR, 3D and CTVL. These results were compared with the findings of fiber optic laryngoscopy and surgery. RESULTS: Combining axial and MPR images, both the accuracy in preoperative tumor staging and the diagnosis of metastatic lymph nodes were 95%. MPR demonstrated more information about the extent of tumor than axial images in 23% cases; 3D image displayed clearly the extension of tumor, the vessels and airway from multiple views. The location, size and extent of tumors found in cranio-caudal CTVL corresponded well with that of laryngoscopy, and CTVL demonstrated the relationship between the tumor and vocal cords and anterior commissure by caudo-cranial approach, which was inaccessible to fiber optic laryngoscopy in 3 cases. CONCLUSIONS: Axial images of helical CT clearly demonstrate the location, size and extent of laryngeal and hypopharyngeal carcinoma, while MPR and 3D images are useful in displaying the three-dimensional images and anatomical relation of the tumor. CTVL can clearly display the mucosal surface structures of the larynx and hypopharynx and is a good complementary method of laryngoscopy. PMID- 11779438 TI - 192Ir endovascular irradiation prevents restenosis after balloon angioplasty in rabbit. AB - OBJECTIVE: To examine the effect of endovascular irradiation on restenosis after balloon angioplasty in rabbit. METHODS: After the establishment of rabbit iliac atherosclerosis model, balloon angioplasty was performed at the lesion segment of the iliac artery. Rabbits were randomly divided into three groups: control group, 10 Gy irradiated group and 18 Gy irradiated group. Endovascular irradiation was performed for irradiated groups at the dilated sites by introducing the 192Ir radioactive guidewire through a catheter. After four weeks, the animals were killed and the target segments were cut down. Histopathologic and morphometric analyses were carried out. RESULTS: The mean final lumen area in the 18 Gy group was larger than that in the control or 10 Gy group (P < 0.05). The intimal area in the 18 Gy group was smaller (P < 0.05). CONCLUSIONS: 192Ir endovascular irradiation may prevent restenosis after balloon angioplasty. The effect is related to the delivered dose. The mechanism is involved in inhibition of neointimal proliferation. PMID- 11779437 TI - Optimal timing of coronary stenting in unstable angina patients. AB - OBJECTIVE: To assess the efficacy and safety of intracoronary stenting in the acute phase of unstable angina pectoris (UAP). METHODS: Fifty-five patients with UAP were randomized to early (Group I, n = 29) and delayed interventional treatment (Group II, n = 26). Coronary angiography and stenting were performed within 48 hours in Group I and 7-10 days later in Group II. Procedural success rate, time interval from admission to angina relief and duration of hospitalization were recorded. Cardiac events within 30 days were observed as well. RESULTS: Clinical characteristics and angiographic features were similar between the two groups. There was no significant difference in the procedural success rate (93% versus 96%), but the cardiac event rate within 30 days was significantly lower in Group I than in Group II (0% versus 9.2%, P < 0.05). The time interval from admission to angina relief (4.4 +/- 3.1 days versus 5.7 +/- 2.9 days) and the duration of hospitalization (8.8 +/- 3.2 days versus 13.5 +/- 3.1 days) were significantly reduced in Group I (both P < 0.05). CONCLUSIONS: Intracoronary stent implantation is effective and safe in the acute phase of UAP. Early percutaneous coronary intervention results in rapid improvement in symptomatology and a shorter hospitalization. Its long-term effect has to be confirmed in a future randomized study. PMID- 11779439 TI - Gene-CYP11B2 expression in rat liver in hepatic fibrogenesis induced by CCl4. AB - OBJECTIVE: To identify aldosterone synthase gene-CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone. METHODS: 160 Wistar rats weighing about 250 g were divided into 4 groups. In the model group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/100 g) subcutaneously three times a week. In the antisterone group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/100 g) subcutaneously three times a week. Antisterone equivalent to 20 mg.kg-1.d-1 was given intragastrically (ig). In the malotilate group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/100 g) subcutaneously three times a week. Malotilate equivalent to 50 mg/kg 1.d-1 was given ig. In the control group (n = 40), the rats were injected with olive oil only. After 2, 4, 6, 8 and 10 weeks, animals were sacrificed, and morphological examination was carried out. The area of collagen was examined with an Image Analyse System. Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization. RESULTS: In situ hybridization and RT-PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred. Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks (P < 0.05). There was no significant difference between the antisterone and malotilate groups (P > 0.05). After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group (P < 0.05). There was no significant difference between the antisterone and model groups (P > 0.05). CONCLUSIONS: The expression of CYP11B2 mRNA is up regulated in fibrotic liver. Antisterone can have a partial fibrogenesis-inhibiting effect in the early stages. PMID- 11779440 TI - Clinical value of sequential subtraction scintigraphy with 99mTc-RBC for gastrointestinal bleeding. AB - OBJECTIVE: To evaluate the clinical value of sequential subtraction scintigraphy (SSS) with 99mTc red blood cell (RBC) for the early detection of gastrointestinal (GI) bleeding. METHODS: Ninety patients referred with clinical evidence of GI bleeding underwent 99mTc-RBC scintigraphy with digital gamma camera after labeling of 99mTc-RBC in vivo. Sequential 12 conventional non-subtraction (CNS) images of abdomen were taken at 5 min intervals for 60 min. Then 5-min images were subsequently subtracted from each other using a computer and 11 subtracted images were obtained. Delayed images up to 24 hr were obtained when early results were negative and/or recurrent bleeding was suspected. RESULTS: 62 of 90 patients with suspected GI bleeding were conformed to have active hemorrhage up to 24 hr. The scintigrams were divided into the following three sets: within 30 min, 60 min, and 24 hr. The sensitivity of SSS was 87% (54/62, 30 min) and 91.9% (57/62, 60 min) respectively, which were significantly higher (P < 0.05) than that of CNS (56.4%, 35/62 and 62.9%, 39/62). 24 hr delayed image of CNS increased the sensitivity to 85.4%. No significant difference in specificity between the two methods was noted. Of the 62 patients with definite active hemorrhage, the bleeding sites were identified by surgical operation in 42. The concordant rate with surgical operation in SSS was 92.8% (39/42), higher than that of CNS (73.8%, 31/42). CONCLUSIONS: Sequential subtraction scintigraphy with 99mTc-RBC, compared with conventional non-subtraction scintigraphy, is an effective technique for the early detection of GI bleeding. It increases the diagnostic sensitivity, detecting a small amount of bleeding earlier than CNS; SSS reduces background activity, more accurtely localizing bleeding sites. It also shortens the examination time, making this approach more suitable for pediatric, elderly and critically ill patients. PMID- 11779441 TI - Prevention and treatment of hepatitis B relapse after liver transplantation. AB - OBJECTIVES: To investigate the effect of orthotopic liver transplantation (OLT) on hepatitis B(HB)-related diseases and the efficiency of prevention and treatment with lamivudine on recurrence of hepatitis B posttransplant in China. METHODS: Orthotopic liver transplantation (OLT) under veno-venous bypass was performed in 10, of whom 9 males had hepatitis B and 1 female had hepatocellular cancer (HCC) without HB pretransplant. Eight of the 9 males had fulminant hepatitis B (FHB) and they all had preoperative serious jaundice, ascites and coagulopathy. Six had encephalopathy; 1 was associated with acute renal failure, and 1 with gastrointestinal hemorrhage. Seven of the 10 patients had lamivudine to prevent reinfection with hepatitis B. RESULTS: Of the 8 patients who have survived for 2-12 months, 7 have survived for 6-12 months. Two died, one of recurrent FHB and the other from multi-organ failure (MOF). Seven preoprative HB patients of the 8 survivors have excellent liver function through 1 has positive HBsAg 6 months after OLT. One of the 8 survivors, the female with HCC pretransplant, suffered hepatitis B 6 months after OLT and her hepatic function has been gradually improving with lamivudine therapy. CONCLUSIONS: OLT is an effective therapy for certain cases of FHB and HCC and lamivudine may prevent recurrence of hepatitis B after OLT. PMID- 11779442 TI - Characterization of hemagglutinin gene of influenza A virus subtype H9N2. AB - OBJECTIVE: To determine the origin of human influenza A (H9N2) virus and the relationship among H9N2 strains isolated from different hosts, on the basis of molecular biology. METHODS: Viruses were passed in embryonated hen eggs, and virion RNA was extracted from allantoic fluid and reverse transcribed to synthesize cDNA. cDNA was amplified by PCR and the PCR product was purified with a purification kit. Afterwards RNA sequence analysis was performed by dideoxynucleotide chain termination and a cloning method. Finally, phylogenetic analysis of the sequencing data was performed with MegAlign (version 1.03) and Editseg (version 3.69) softwares. RESULTS: The amino acid sequences at the cleavage site between HA1 and HA2 domains of H9N2 viruses isolated in China are R S-S-R. One pigeon strain contains seven potential glycosylation sites on the HA protein molecule, while all others have eight. There are 2 to 15 differences of amino acid sequences distributed at 24 different positions on the HA protein molecules among six H9N2 viruses. The H9N2 viruses with multiple lineages of HA genes were co-circulating in China recently. CONCLUSION: The highest possibility is that human influenza A (H9N2) virus was derived from Chicken H9N2 virus, and not derived from pigeon H9N2 virus. However, it is still unknown whether the H9N2 virus could transmit from person to person. The H9N2 viruses with multiple lineages of HA genes are co-circulating in China. PMID- 11779443 TI - Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease. AB - OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide. PMID- 11779444 TI - Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry. AB - OBJECTIVE: To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. METHODS: Retrospective review of outpatient records. RESULTS: 1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P < 0.05). CONCLUSION: In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies. PMID- 11779445 TI - Pathologic features of occult lymphatic metastasis in supraglottic carcinoma. AB - OBJECTIVE: To study the pathologic features of occult lymphatic metastasis in supraglottic carcinoma. METHODS: Serial sections of 153 neck dissection specimens in 100 patients with supraglottic carcinoma were evaluated under the microscope. RESULTS: In 100 patients, 38 had occult metastatic lymph nodes. 51 metastatic lymph nodes were found in pathology, and their sizes ranged from 0.5 cm to 2.6 cm (average 1.1 cm). The distribution of 51 lymph nodes was 1 in level I (2%), 37 in level II (73%), 12 in level III (24%), and 1 in level IV (2%). Among the 51 nodes, 21 (41%) were early stage, 18 (35%) were growth stage, 7 (14%) were tull stage, and 5 (10%) were extracapsular stage. The differentiation degree and appearance of supraglottic carcinoma was not directly related with occult metastasis. CONCLUSION: The occult metastatic rate of supraglottic carcinoma is high, and selective neck dissection may be necessary. PMID- 11779446 TI - Enterococcal urinary tract infections: eight years experience at a regional hospital in Trinidad, West Indies. AB - OBJECTIVE: To investigate the prevalence of significant enterococcal isolates from urine and determine what factors are associated with the increased prevalence, with particular reference to antibiotic susceptibilities. METHODS: Retrospective analysis over an 8-year period of hospital laboratory records of urinary isolates of enterococci was done. Species were identified via colony morphology, growth in 6.5% sodium chloride and their ability to hydrolyze esculin in the presence of 40% bile salts. Susceptibility testing via the disc diffusion technique with 9 commonly used antibiotics was also done as defined by the National Committee for Clinical Laboratory Standards. RESULTS: From 39,881 urine specimens, 9116 (22.9%) were culture positive. Of this 9116, 1001 (11.0%) were enterococci, the 4th most common urinary isolate. E. coli was the most common (36.2%). Most enterococci were from pediatric patients (28.4%) and the urology unit (24.5%). All enterococci were fully sensitive to ampicillin and augmentin (amoxicillin-clavulanic acid). Sensitivity to gentamicin decreased significantly from 79% in 1990 to 58% in 1997 (P < 0.005). Sensitivity to the cephalosporins and nitrofuratoin were relatively stable, but sensitivity to nalidixic acid varied. No resistance to vancomycin was detected during the study, and no cases of bacteremia complicated bacteriuria were seen. CONCLUSION: Isolation of enterococci was relatively stable during the 8-year period, and all isolates were fully sensitive to the older beta-lactams, ampicillin, cefaclor and augmentin, but displayed varying degrees of multi-resistance to other commonly used urinary agents such as nalidixic acid and co-trimoxazole (trimethoprim-sulfamethoxazole). Because of the emergence of multi-resistant enterococci in many countries, and the high cost of drugs in our society, it is imperative that vigilance be maintained in monitoring enterococcal infections in hospitals. PMID- 11779447 TI - Endocytic routes of exogenous antigen in murine dendritic cells and macrophages. AB - OBJECTIVE: To compare the endocytic routes of exogenous antigen between murine dendritic cells (DCs) and macrophages (M phi s). METHODS: Murine bone marrow derived DCs and peritoneal M phi s were pulsed with horseradish peroxidase (HRP) 5 nm colloidal gold for 10 minutes, then grouped and chased for 0-120 minutes in culture medium. Intracellular distribution of 5 nm colloidal gold was explored by means of the cellular enzymatic-chemistry of acid phosphatase and MHC II immuno cytochemistry under electron microscope. RESULTS: After 10 minutes of pulse with HRP-5 nm colloidal gold and 30 minutes of chase, most HRP-5 nm gold particles internalized by DCs entered into MHC class II compartments (M II Cs), and a small portion entered into acid phosphatase-positive lysosomes. In contrast to DCs, most M phi s lysosomes were accessed by HRP-5 nm gold particles, and a small portion of HRP-5 nm gold particles entered into M II Cs. After 60 minutes of chase, 5 nm gold particles could hardly be seen within M phi s, whereas most 5 nm gold particles were still retained in DCs. CONCLUSIONS: The endocytic route of exogenous antigen in DCs seems to be different from that in M phi s. Antigens taken by M phi s mainly enter into lysosomes within 30 minutes. In the case of DCs, most internalized antigens enter into M II Cs, which may be related to their unique antigen-presenting function. In addition, M phi s seem to have more powerful capacity to scavenge exogenous antigen than DCs. PMID- 11779448 TI - Transmission of the Y chromosome microdeletion to a baby boy conceived after intracytoplasmic sperm injection. PMID- 11779449 TI - Cut and puncture accidents involving health care workers exposed to biological materials. AB - The first report of occupational acquisition of HIV appeared in 1984, and, by June, 1997, the Centers for Disease Control and Prevention (CDC) had reported 52 documented cases of sero-conversion following occupational exposure to HIV-1 by health care workers of those cases. 47 (90.3%) were exposed to blood. The most frequent type of accident reported was percutaneous needlestick injury. Prospective studies have estimated that the risk of HIV transmission following percutaneous exposure to infected blood is 0.3% (Confidence Interval 95% = 0.2% to 0.5%). Following a mucous membrane exposure, the risk is 0.09% (CI 95% = 0.006% to 0.5%). The risk of hepatitis B acquisition ranges from 6% to 30%, and hepatitis C acquisition, 3% to 10%. Since 1992, the Sao Paulo Hospital s Hospital Infection Prevention and Control Service (SPCIH) has notified and treated all workers exposed to accidents involving biological materials. In the last six years, we have handled approximately 1,300 cases of reported accidents, of which 90% were percutaneous, most involving needlesticks. Such cases were frequently caused by the inadequate disposal and recapping of needles. In these accidents, 20% of the source patients were HIV positive, 10% were hepatitis C positive, and 7.6% were hepatitis B positive. This review summarizes the guidelines for a standardized response when dealing with accidents involving health care workers. Transmission of hepatitis B and HIV can be reduced if adequate preventive measures are taken in advance. If proper prophylaxis is not being done, it should be initiated immediately. PMID- 11779450 TI - In vitro antimicrobial activity of linezolid tested against vancomycin-resistant enterococci isolated in Brazilian hospitals. AB - The emergence of vancomycin-resistant enterococci (VRE) has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis), were analyzed. Strains were isolated from patients at Sao Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Publico Estadual, Santa Marcelina Hospital, Santa Casa de Misericordia de Sao Paulo, and Hospital de Clinicas do Parana. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE). Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil. PMID- 11779451 TI - Detection of mycobacteria in the bloodstream of patients with acquired immunodeficiency syndrome in a university hospital in Brazil. AB - This study was done to determine the occurrence of mycobacteria in the bloodstreams of patients with fever and advanced AIDS in a Brazilian hospital. We also verified the capability of an automated method for recovering these bacteria. During a period of 19 months, 254 patients with AIDS were evaluated. Blood cultures were generally submitted in pairs and drawn separately. Blood cultures were processed by the BACTEC 460TB System (Becton Dickinson Microbiology Systems, Sparks, MD), using the Bactec 13A media (Becton Dickinson Microbiology Systems, Sparks, MD). Of the 530 vials submitted, 77 (14.5%) from 41 (16%) patients were positive. Mycobacterium avium complex was recovered from 45 (58.4%) of the 77 positive vials, corresponding to 22 (53.6%) patients with positive blood cultures. The average time to detect Mycobacterium avium complex was 15 days. Mycobacterium tuberculosis was recovered from 26 (33.8%) of the 77 positive vials, corresponding to 15 (36.6%) patients with positive blood cultures, with an average detection time of 24 days. Other species of mycobacteria were recovered from 6 (7.8%) of the 77 vials, corresponding to 4 (9.8%) patients. M.avium complex was fairly prevalent (8.7%) in severely ill patients with AIDS in our hospital. M. tuberculosis was also an important (6.0%) agent of systemic bacterial infections in these patients. The rapid diagnosis of mycobacteremia was possible with the implementation of this automated technology. PMID- 11779452 TI - An epidemiological study of Haemophilus influenzae at a Brazilian day care center. AB - Day care centers are a relatively new phenomenon in Brazil that bring together large numbers of young children susceptible to contagious diseases. Haemophilus influenzae (Hi) is an important infection in the age range of those attending day care centers. In the present study, the carriage rate of Haemophilus influenzae was identified in 38 day care attendees age 6 to 37 months, and 23 staff members, at a day care center in Ribeirao Preto-Sao Paulo, in 1997. To identify the carriers, two nasopharyngeal swabs were collected; one in July and one in December. The rate of H. influenzae carriers among the children was 77%. Only 2 of 23 staff members (9%) had Hi. Among the children, there were 58 isolates in the two sampling periods; 6 of the Hi were serotype b, 1 was serotype e, and 48 isolates were non-typeable. Two were identified as H. parainfluenzae. One adult had a non-typeable Hi and 1 had H. paraphrohaemolyticus. Three of the 6 children with type B had received a conjugate vaccine against H. influenzae type b, but they still carried this bacterium in the nasopharynx (50%). Forty ribotype patterns were found among the isolates, showing a high exchange rate of nontypeable H. influenzae carriers. The results indicate that, because of the high and changing biotype of Hi carriage, day care centers should be carefully monitored as potential point source of HI disease in the community. PMID- 11779453 TI - In vitro susceptibility of gram-positive cocci isolated from skin and respiratory tract to azithromycin and twelve other antimicrobial agents. AB - This study was conducted to evaluate the activity of azithromycin in comparison to 12 other antibacterial agents against recent isolates obtained consecutively from patients with respiratory tract or skin infections, from January to July, 2000. A total of 717 Gram-positive cocci were analyzed in this study and the following species were studied: Staphylococcus aureus (n=576), beta-hemolytic streptococci (n=115), and Streptococcus pneumoniae (n=26). Susceptibility testing was carried out by the disk diffusion method and interpreted according to NCCLS breakpoints. The activity of azithromycin was compared to erythromycin, clindamycin, chloramphenicol, ciprofloxacin, ofloxacin, oxacillin, penicillin, ceftriaxone, tetracycline, trimethoprim/sulfamethoxazole, teicoplanin, and vancomycin. Of the 26 S. pneumoniae isolates recovered from the respiratory tract, 5 (19.2%) were intermediate resistant to penicillin. All of these strains were susceptible to chloramphenicol, ofloxacin, and vancomycin, and 24 (92%) were also susceptible to azithromycin, clindamycin, and erythromycin. Among the 67 beta-hemolytic streptococci strains isolated from the respiratory tract, 66 (99%) were susceptible to azithromycin, erythromycin, clindamycin, and ofloxacin. All 48 beta-hemolytic streptococci strains isolated from skin were susceptible to azithromycin and clindamycin, 47 (98%) were susceptible to erythromycin, and 46 (96%) were susceptible to ofloxacin. Of the 576 strains of S. aureus, 253 (43.9%) were isolated from the respiratory tract and 323 (56.1%) from skin. Among S. aureus isolates from the respiratory tract and skin, 46 (18%) and 78 (24%), respectively were resistant to oxacillin. Isolates from the respiratory tract and skin showed the same percentage of resistance (36%) to azithromycin. These in vitro results suggest that azithromycin can be a therapeutic option for treatment of infections caused by these bacteria since the newer macrolides have several distinct advantages over erytromycin including improved oral bioavailability, longer half-life allowing once or twice daily administration, higher tissue concentrations and less gastrointestinal adverse effects. PMID- 11779454 TI - Leptospirosis mimicking sepsis after orthopedic surgery: a case report. AB - We report a case of leptospirosis that occurred after elective surgery involving tendon transfer and shoulder arthroscopy. The disease mimicked hospital infection after orthopedic surgery and was at first misdiagnosed as post-operative sepsis. The patient was 60 year old female that developed sepsis with hypotension, shock, bleeding, jaundice and renal insufficiency 4 hours after surgery. Shock treatment procedures were performed and broad spectrum antibiotic therapy was used with coverage for bacteria acquired in hospitals. A careful investigation was carried out by the Hospital Infection Control Service in search of the possible source of the infection. After clinical evaluation by a specialist in infectious diseases, the hypothesis of leptospirosis was put forward based on clinical and epidemiological data. The hypothesis was later confirmed by the positive result of serological tests with the microagglutination method that yielded 1:800 and then 1:12,600 7 days later. This is the first reported case of leptospirosis manifest directly following surgery, mimicking postoperative sepsis. PMID- 11779455 TI - Syphilitic meningitis in HIV-patients with meningeal syndrome: report of two cases and review. AB - Few patients with symptomatic neurosyphilis present with signs and symptoms of acute meningitis. Here we report two cases of syphilitic meningitis diagnosed in HIV patients with meningeal syndrome. The first case, a 30-year-old black bisexual male, had concurrent meningeal and ocular syphilis with persistent unusually low CSF glucose levels. He responded well to 21 days of intravenous penicillin therapy. The second case was a 55-year-old female with epilepsy, depression, behavioral disorder and confusion. The diagnosis of HIV infection was made after onset of the syphilitic meningitis. She was treated with 21 days i.v. penicillin with improvement in her clinical condition. The clinical aspects of combined neurosyphilis and HIV infection, plus special features of diagnosis and treatment are discussed. PMID- 11779456 TI - Why is p53 acetylated? AB - Recent studies suggest that acetylation of the p53 tumor suppressor protein is not important for its DNA binding activity, as was previously thought. We discuss here a number of theories as to how this modification may serve to regulate the protein's functions. PMID- 11779457 TI - Multisite phosphorylation and the countdown to S phase. AB - Remarkably, SCF(Cdc4) ubiquitin ligase binds and ubiquitinates Sic1 decorated with six, but not five, phosphates. This numerical wizardry suggests how analog inputs can be rectified to digital outputs. Unraveling the counting mechanism promises to generate new insights into the architecture of protein nanoprocessors. PMID- 11779458 TI - microRNAs: tiny regulators with great potential. AB - Animal genomes contain an abundance of small genes that produce regulatory RNAs of about 22 nucleotides in length. These microRNAs are diverse in sequence and expression patterns, and are evolutionarily widespread, suggesting that they may participate in a wide range of genetic regulatory pathways. PMID- 11779459 TI - The unfolding tale of the unfolded protein response. AB - Surface and secreted proteins are synthesized in the endoplasmic reticulum where they must fold and assemble before being transported. Changes in the ER that interfere with their proper maturation initiate the unfolded protein response pathway. New studies have filled in a missing link between the yeast and mammalian pathways. PMID- 11779460 TI - Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila. AB - The JAK/STAT signaling pathway, renowned for its effects on cell proliferation and survival, is constitutively active in various human cancers, including ovarian. We have found that JAK and STAT are required to convert the border cells in the Drosophila ovary from stationary, epithelial cells to migratory, invasive cells. The ligand for this pathway, Unpaired (UPD), is expressed by two central cells within the migratory cell cluster. Mutations in upd or jak cause defects in migration and a reduction in the number of cells recruited to the cluster. Ectopic expression of either UPD or JAK is sufficient to induce extra epithelial cells to migrate. Thus, a localized signal activates the JAK/STAT pathway in neighboring epithelial cells, causing them to become invasive. PMID- 11779461 TI - Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. AB - Wnt signaling via the Frizzled (Fz) receptor controls cell polarity and movement during development, but the molecular nature of Wnt/Fz polarity signal transduction remains poorly defined. Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture. Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled (Dvl) and a novel Formin homology protein Daam1. Daam1 binds to both Dvl and Rho, and mediates Wnt-induced Dvl-Rho complex formation. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling. Our study illustrates a molecular pathway from Wnt/Fz signaling to Rho activation in cell polarity signal transduction. PMID- 11779462 TI - Posttranslational mechanisms regulate the mammalian circadian clock. AB - We have examined posttranslational regulation of clock proteins in mouse liver in vivo. The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation. These proteins, the cryptochromes (mCRY1 and mCRY2), and casein kinase I epsilon (CKIepsilon) form multimeric complexes that are bound to DNA during negative transcriptional feedback. CLOCK:BMAL1 heterodimers remain bound to DNA over the circadian cycle. The temporal increase in mPER abundance controls the negative feedback interactions. Analysis of clock proteins in mCRY-deficient mice shows that the mCRYs are necessary for stabilizing phosphorylated mPER2 and for the nuclear accumulation of mPER1, mPER2, and CKIepsilon. We also provide in vivo evidence that casein kinase I delta is a second clock relevant kinase. PMID- 11779463 TI - ATP-bound states of GroEL captured by cryo-electron microscopy. AB - The chaperonin GroEL drives its protein-folding cycle by cooperatively binding ATP to one of its two rings, priming that ring to become folding-active upon GroES binding, while simultaneously discharging the previous folding chamber from the opposite ring. The GroEL-ATP structure, determined by cryo-EM and atomic structure fitting, shows that the intermediate domains rotate downward, switching their intersubunit salt bridge contacts from substrate binding to ATP binding domains. These observations, together with the effects of ATP binding to a GroEL GroES-ADP complex, suggest structural models for the ATP-induced reduction in affinity for polypeptide and for cooperativity. The model for cooperativity, based on switching of intersubunit salt bridge interactions around the GroEL ring, may provide general insight into cooperativity in other ring complexes and molecular machines. PMID- 11779464 TI - XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. AB - In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR). In mammals, no Hac1p counterpart has yet been discovered despite the presence of Ire1p homologs in the endoplasmic reticulum. Instead, the transcription factor ATF6 specific to the mammalian UPR is regulated by intramembrane proteolysis. Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways. PMID- 11779465 TI - Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. AB - The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). We have used C. elegans as a genetic model system to dissect UPR signaling in a multicellular organism. C. elegans requires ire-1-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress. In addition, ire-1/xbp-1 acts with pek 1, a protein kinase that mediates translation attenuation, in complementary pathways that are essential for worm development and survival. We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development. PMID- 11779466 TI - Meiotic silencing by unpaired DNA. AB - The silencing of gene expression by segments of DNA present in excess of the normal number is called cosuppression in plants and quelling in fungi. We describe a related process, meiotic silencing by unpaired DNA (MSUD). DNA unpaired in meiosis causes silencing of all DNA homologous to it, including genes that are themselves paired. A semidominant Neurospora mutant, Sad-1, fails to perform MSUD. Sad-1 suppresses the sexual phenotypes of many ascus-dominant mutants. MSUD may provide insights into the function of genes necessary for meiosis, including genes for which ablation in vegetative life would be lethal. It may also contribute to reproductive isolation of species within the genus Neurospora. The wild-type allele, sad-1(+), encodes a putative RNA-directed RNA polymerase. PMID- 11779467 TI - Yeast DNA polymerase eta utilizes an induced-fit mechanism of nucleotide incorporation. AB - DNA polymerase eta (Poleta) is unique among eukaryotic DNA polymerases in its proficient ability to replicate through distorting DNA lesions, and Poleta synthesizes DNA with a low fidelity. Here, we use pre-steady-state kinetics to investigate the mechanism of nucleotide incorporation by Poleta and show that it utilizes an induced-fit mechanism to selectively incorporate the correct nucleotide. Poleta discriminates poorly between the correct and incorrect nucleotide at both the initial nucleotide binding step and at the subsequent induced-fit conformational change step, which precedes the chemical step of phosphodiester bond formation. This property enables Poleta to bypass lesions with distorted DNA geometries, and it bestows upon the enzyme a low fidelity. PMID- 11779468 TI - Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. AB - Pseudouridine (Psi) synthases catalyze the isomerization of specific uridines in cellular RNAs to pseudouridines and may function as RNA chaperones. TruB is responsible for the Psi residue present in the T loops of virtually all tRNAs. The close homolog Cbf5/dyskerin is the catalytic subunit of box H/ACA snoRNPs. These carry out the pseudouridylation of eukaryotic rRNA and snRNAs. The 1.85 A resolution structure of TruB bound to RNA reveals that this enzyme recognizes the preformed three-dimensional structure of the T loop, primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA. Structural comparisons with TruB demonstrate that all Psi synthases are descended from a common molecular ancestor. PMID- 11779470 TI - A genetic basis for obsessive grooming. AB - Excessive grooming behaviors, cleansing rituals, and self-mutilation are important features of a range of neuropsychiatric diseases including obsessive compulsive (OC)-spectrum disorders. In this issue of Neuron, Greer and Capecchi (2002) report that Hoxb8 mutant mice exhibit this behavioral phenotype. These Hoxb8 mutants will be valuable in exploring the genetics and pathophysiology of OC-spectrum disorders as well as strategies for their treatment. PMID- 11779471 TI - Conserved cues for axon and dendrite growth in the developing cortex. AB - The cellular and molecular mechanisms that guide axonal and dendritic differentiation in the cerebral cortex are just beginning to be defined. Many of the molecular signals that guide axons also, and sometimes simultaneously, influence dendritic growth. Whitford et al. (2002 [this issue of Neuron]) demonstrate that in addition to their roles in axon guidance and cell migration cue, Slit proteins can also regulate dendritic growth. PMID- 11779472 TI - GABARAP and GABA(A) receptor clustering. AB - Coyle et al. (2002), in this issue of Neuron, reveal the crystal structure for the GABA(A) receptor binding protein, GABARAP. They show GABARAP can switch from a monomer to an extended linear polymer form that may function to assemble microtubules during the intracellular trafficking or postsynaptic clustering of GABA(A) receptors. PMID- 11779473 TI - Gi Irks GIRKs. AB - G protein-activated potassium channels (GIRKs), monitored with the temporal and molecular resolution of electrophysiology, play a key role in the study of signal transduction. GIRKs are activated primarily by the G(beta)(gamma) subunits, but a paper by Peleg et al. (2002 [this issue of Neuron]) demonstrates a role for G(alpha) subunits in suppressing basal activity and supports the idea of a macromolecular complex of G protein, GIRK, and perhaps RGS protein. PMID- 11779474 TI - Neurotrophins: to cleave or not to cleave. AB - The family of neurotrophic factors known as neurotrophins has yielded a series of surprises, both with regard to the broad extent of their functional roles and the remarkable complexity of their signaling mechanisms. The recent discovery that a neurotrophin precursor protein and its proteolytically processed products may differentially activate pro- and antiapoptotic cellular responses, through preferential activation of Trk or p75 receptors, promises to unveil yet another level of regulatory complexity. PMID- 11779476 TI - Selective photostimulation of genetically chARGed neurons. AB - To permit direct functional analyses of neural circuits, we have developed a method for stimulating groups of genetically designated neurons optically. Coexpression of the Drosophila photoreceptor genes encoding arrestin-2, rhodopsin (formed by liganding opsin with retinal), and the alpha subunit of the cognate heterotrimeric G protein--an explosive combination we term "chARGe"--sensitizes generalist vertebrate neurons to light. Illumination of a mixed population of neurons elicits action potentials selectively and cell-autonomously in its genetically chARGed members. In contrast to bath-applied photostimulants or caged neurotransmitters, which act indiscriminately throughout the illuminated volume, chARGe localizes the responsiveness to light. Distributed activity may thus be fed directly into a circumscribed population of neurons in intact tissue, irrespective of the spatial arrangement of its elements. PMID- 11779477 TI - Hoxb8 is required for normal grooming behavior in mice. AB - Repertoires of grooming behaviors critical to survival are exhibited by most animal species, including humans. Genes that influence this complex behavior are unknown. We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions. Additionally, these mice excessively groom normal cagemates. We have been unable to detect any skin or PNS abnormalities in Hoxb8 mutants. These observations suggest that the excessive, pathological grooming exhibited by these mice results from CNS abnormalities. Consistent with this interpretation, we demonstrate Hoxb8 expression in regions of the adult mouse CNS previously implicated in the control of grooming. The aberrant behavior observed in Hoxb8 mutants is not unlike that of humans suffering from the OC-spectrum disorder, trichotillomania. Interestingly, Hoxb8 is expressed in regions of the CNS known as the "OCD circuit." PMID- 11779478 TI - Drosophila JAB1/CSN5 acts in photoreceptor cells to induce glial cells. AB - Different classes of photoreceptor neurons (R cells) in the Drosophila compound eye form connections in different optic ganglia. The R1-R6 subclass connects to the first optic ganglion, the lamina, and relies upon glial cells as intermediate targets. Conversely, R cells promote glial cell development including migration of glial cells into the target region. Here, we show that the JAB1/CSN5 subunit of the COP9 signalosome complex is expressed in R cells, accumulates in the developing optic lobe neuropil, and through the analysis of a unique set of missense mutations, is required in R cells to induce lamina glial cell migration. In these CSN5 alleles, R1-R6 targeting is disrupted. Genetic analysis of protein null alleles further revealed that the COP9 signalosome is required at an earlier stage of development for R cell differentiation. PMID- 11779479 TI - Regulation of cortical dendrite development by Slit-Robo interactions. AB - Slit proteins have previously been shown to regulate axon guidance, branching, and neural migration. Here we report that, in addition to acting as a chemorepellant for cortical axons, Slit1 regulates dendritic development. Slit1 is expressed in the developing cortex, and exposure to Slit1 leads to increased dendritic growth and branching. Conversely, inhibition of Slit-Robo interactions by Robo-Fc fusion proteins or by a dominant-negative Robo attenuates dendritic branching. Stimulation of neurons transfected with a Met-Robo chimeric receptor with Hepatocyte growth factor leads to a robust induction of dendritic growth and branching, suggesting that Robo-mediated signaling is sufficient to induce dendritic remodeling. These experiments indicate that Slit-Robo interactions may exert a significant influence over the specification of cortical neuron morphology by regulating both axon guidance and dendritic patterning. PMID- 11779480 TI - Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. AB - GABARAP recognizes and binds the gamma2 subunit of the GABA(A) receptor, interacts with microtubules and the N-ethyl maleimide sensitive factor, and is proposed to function in GABA(A) receptor trafficking and postsynaptic localization. We have determined the crystal structure of human GABARAP at 1.6 A resolution. The structure comprises an N-terminal helical subdomain and a ubiquitin-like C-terminal domain. Structure-based mutational analysis demonstrates that the N-terminal subdomain is responsible for tubulin binding while the C-terminal domain contains the binding site for the GABA(A). A second GABARAP crystal form was determined at 1.9 A resolution and documents that GABARAP can self-associate in a head-to-tail manner. The structural details of this oligomerization reveal how GABARAP can both promote tubulin polymerization and facilitate GABA(A) receptor clustering. PMID- 11779481 TI - Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating. AB - Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. The M3 segment, as well as more superficial parts of the extracellular vestibule, undergo extensive remodeling during channel closure, but do not define the activation gate, which is located deeper in the pore. Rather, the pore walls lining the extracellular vestibule constrict during channel closure. This movement is essential for coupling ligand binding to activation gate opening and accounts for the different mechanisms of open channel block, including trapping. PMID- 11779482 TI - G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK. AB - GIRK (Kir3) channels are activated by neurotransmitters coupled to G proteins, via a direct binding of G(beta)(gamma). The role of G(alpha) subunits in GIRK gating is elusive. Here we demonstrate that G(alpha)(i) is not only a donor of G(beta)(gamma) but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or G(beta)(gamma). Coexpression of G(alpha)(i3) or G(alpha)(i1) restores the correct gating parameters. G(alpha)(i) acts neither as a pure G(beta)(gamma) scavenger nor as an allosteric cofactor for G(beta)(gamma). It inhibits only the basal activity without interfering with G(beta)(gamma)-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. G(alpha)(i) probably acts in its GDP bound form, alone or as a part of G(alpha)(beta)(gamma) heterotrimer. PMID- 11779483 TI - Endogenous calcium buffers regulate fast exocytosis in the synaptic terminal of retinal bipolar cells. AB - Calcium-triggered exocytosis at the synapse is suppressed by addition of calcium chelators, but the effects of endogenous Ca(2+) buffers have not been tested. We find that 80% of Ca(2+) binding sites in the synaptic terminal of retinal bipolar cells were associated with mobile molecules that suppressed activation of Ca(2+) sensitive K(+) channels with an efficiency equivalent to approximately 1.2 mM BAPTA. Removing these buffers caused a 30-fold increase in the number of vesicles released by Ca(2+) tail currents lasting approximately 0.5 ms and a 2-fold increase in the rapidly releasable pool of vesicles (RRP). The effects of BAPTA and EGTA indicate that vesicles comprising the RRP were docked at variable distances from Ca(2+) channels. We propose that endogenous Ca(2+) buffers regulate the size of the RRP by suppressing the release of vesicles toward the periphery of the active zone. PMID- 11779484 TI - Bradykinin and ATP accelerate Ca(2+) efflux from rat sensory neurons via protein kinase C and the plasma membrane Ca(2+) pump isoform 4. AB - Modulation of Ca(2+) channels by neurotransmitters provides critical control of neuronal excitability and synaptic strength. Little is known about regulation of the Ca(2+) efflux pathways that counterbalance Ca(2+) influx in neurons. We demonstrate that bradykinin and ATP significantly facilitate removal of action potential-induced Ca(2+) loads by stimulating plasma membrane Ca(2+)-ATPases (PMCAs) in rat sensory neurons. This effect was mimicked in the soma and axonal varicosities by phorbol esters and was blocked by antagonists of protein kinase C (PKC). Reduced expression of PMCA isoform 4 abolished, and overexpression of isoform 4b enhanced, PKC-dependent facilitation of Ca(2+) efflux. This acceleration of PMCA4 underlies the shortening of the action potential afterhyperpolarization produced by activation of bradykinin and purinergic receptors. Thus, isoform-specific modulation of PMCA-mediated Ca(2+) efflux represents a novel mechanism to control excitability in sensory neurons. PMID- 11779485 TI - Involvement of presynaptic N-methyl-D-aspartate receptors in cerebellar long-term depression. AB - At the cerebellar synapses between parallel fibers (PFs) and Purkinje cells (PCs), long-term depression (LTD) of the excitatory synaptic current has been assumed to be independent of the N-methyl-D-aspartate (NMDA) receptor activation because PCs lack NMDA receptors. However, we now report that LTD is suppressed by NMDA receptor antagonists that act on presynaptic NMDA receptors of the PFs. This effect is still observed when the input is restricted to a single fiber. Therefore, LTD does not require the spatial integration of multiple inputs. In contrast, it involves a temporal integration, since reliable LTD induction requires the PFs to fire two action potentials in close succession. This implies that LTD will selectively depress the response to a burst of presynaptic action potentials. PMID- 11779486 TI - Opponent inhibition: a developmental model of layer 4 of the neocortical circuit. AB - We model the development of the functional circuit of layer 4 (the input recipient layer) of cat primary visual cortex. The observed thalamocortical and intracortical circuitry codevelop under Hebb-like synaptic plasticity. Hebbian development yields opponent inhibition: inhibition evoked by stimuli anticorrelated with those that excite a cell. Strong opponent inhibition enables recognition of stimulus orientation in a manner invariant to stimulus contrast. These principles may apply to cortex more generally: Hebb-like plasticity can guide layer 4 of any piece of cortex to create opposition between anticorrelated stimulus pairs, and this enables recognition of specific stimulus patterns in a manner invariant to stimulus magnitude. Properties that are invariant across a cortical column are predicted to be those shared by opponent stimulus pairs; this contrasts with the common idea that a column represents cells with similar response properties. PMID- 11779487 TI - The effect of gaze angle and fixation distance on the responses of neurons in V1, V2, and V4. AB - What we see depends on where we look. This paper characterizes the modulatory effects of point of regard in three-dimensional space on responsiveness of visual cortical neurons in areas V1, V2, and V4. Such modulatory effects are both common, affecting 85% of cells, and strong, frequently producing changes of mean firing rate by a factor of 10. The prevalence of neurons in area V4 showing a preference for near distances may be indicative of the involvement of this area in close scrutiny during object recognition. We propose that eye-position signals can be exploited by visual cortex as classical conditioning stimuli, enabling the perceptual learning of systematic relationships between point of regard and the structure of the visual environment. PMID- 11779493 TI - Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans. AB - The recombination mechanisms that deal with double-strand breaks in organisms as diverse as phage, bacteria, yeast, and humans are remarkably conserved. We discuss conservation in the biochemical pathways required to recombine DNA ends and in the structure of the DNA products. In addition, we highlight that two fundamentally distinct broken DNA substrates exist and describe how they are repaired differently by recombination. Finally, we discuss the need to coordinate recombinational repair with cell division through DNA damage response pathways. PMID- 11779494 TI - DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. AB - DNA ligase IV functions in DNA nonhomologous end-joining and V(D)J recombination. Four patients with features including immunodeficiency and developmental and growth delay were found to have mutations in the gene encoding DNA ligase IV (LIG4). Their clinical phenotype closely resembles the DNA damage response disorder, Nijmegen breakage syndrome (NBS). Some of the mutations identified in the patients directly disrupt the ligase domain while others impair the interaction between DNA ligase IV and Xrcc-4. Cell lines from the patients show pronounced radiosensitivity. Unlike NBS cell lines, they show normal cell cycle checkpoint responses but impaired DNA double-strand break rejoining. An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions. PMID- 11779495 TI - Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions. AB - Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis. PMID- 11779496 TI - Visualization of mismatch repair in bacterial cells. AB - We determined the localizations of mismatch repair proteins in living Bacillus subtilis cells. MutS-GFP colocalized with the chromosome in all cells and formed foci in a subset of cells. MutL-GFP formed foci in a subset of cells, and its localization was MutS dependent. The introduction of mismatches by growth in 2 aminopurine caused a replication-dependent increase in the number of cells with MutS and MutL foci. Approximately half of the MutS foci colocalized with DNA polymerase foci. We conclude that MutS is associated with the entire chromosome, poised to detect mismatches. After detection, it appears that mismatch repair foci assemble at mismatches as they emerge from the DNA polymerase and are then carried away from the replisome by continuing replication. PMID- 11779497 TI - Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. AB - Methylation of histone H3 at lysine 9 by SUV39H1 and subsequent recruitment of the heterochromatin protein HP1 has recently been linked to gene silencing. In addition to lysine 9, histone H3 methylation also occurs at lysines 4, 27, and 36. Here, we report the purification, molecular identification, and functional characterization of an H3-lysine 4-specific methyltransferase (H3-K4-HMTase), SET7. We demonstrate that SET7 methylates H3-K4 in vitro and in vivo. In addition, we found that methylation of H3-K4 and H3-K9 inhibit each other. Furthermore, H3-K4 and H3-K9 methylation by SET7 and SUV39H1, respectively, have differential effects on subsequent histone acetylation by p300. Thus, our study provides a molecular explanation to the differential effects of H3-K4 and H3-K9 methylation on transcription. PMID- 11779498 TI - Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity. AB - We have dissected the steps in nucleosome remodeling by BRG1, the ATPase subunit of human SWI/SNF. BRG1-catalyzed DNA exposure is not enhanced by the proximity of the site to the ends of nucleosomal DNA, suggesting that the mechanism involves more than peeling or sliding of the DNA. Comparison of DNA exposure at specific sites with overall changes in the path of DNA implies that BRG1 generates multiple distinct remodeled structures and continuously interconverts them. These characteristics are shared by the entire SWI/SNF complex and have parallels, as well as interesting differences, with the activities of GroEL and Hsp70 protein chaperones. The chaperone-like activity of SWI/SNF is expected to create multiple opportunities for the binding of distinct regulatory factors, providing one mechanism by which SWI/SNF family complexes can contribute to both activation and repression of transcription. PMID- 11779499 TI - Independent dynamic regulation of histone phosphorylation and acetylation during immediate-early gene induction. AB - Induction of c-fos and c-jun is associated with phosphoacetylation of histone H3 and acetylation of histone H4. Upon induction, a large population of nucleosomes becomes highly acetylated on histones H3 and H4, whereas a much smaller population of comparable nucleosomes at similar positions along the gene becomes phosphoacetylated. Inhibiting histone H3 phosphorylation with kinase inhibitors does not measurably alter the enhanced acetylation of these nucleosomes. Finally, whereas H3 phosphorylation is a MAP kinase-mediated inducible event, we found acetylation to be continuously turning over by the targeted action of HATs and HDACs in the absence of any stimulation or gene transcription. These studies suggest that phosphorylation and acetylation are independently and dynamically regulated at these genes and reveal the complexity of multiple histone modifications at immediate-early gene chromatin. PMID- 11779500 TI - Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. AB - Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity. Acetylation site substitutions reduced p53-dependent transcriptional induction and G1 cell cycle arrest. Chromatin immunoprecipitation analysis of the endogenous p21 promoter showed increased association of p53, coactivators (CBP and TRRAP), and acetylated histones following cell irradiation. Results with acetylation-defective p53 demonstrate that the critical function of acetylation is not to increase the DNA binding affinity of p53 but rather to promote coactivator recruitment and histone acetylation. Therefore, we propose that an acetylation cascade consisting of p53 acetylation-dependent recruitment of coactivators/HATs is crucial for p53 function. PMID- 11779501 TI - Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis. AB - The BRCA1-associated protein BARD1 is a putative tumor suppressor. We suggest that BARD1 is a mediator of apoptosis since (1) cell death in vivo (ischemic stroke) and in vitro is accompanied by increased levels of BARD1 protein and mRNA; (2) overexpression of BARD1 induces cell death with all features of apoptosis; and (3) BARD1-repressed cells are defective for the apoptotic response to genotoxic stress. The proapoptotic activity of BARD1 involves binding to and elevations of p53. BRCA1 is not required for but partially counteracts apoptosis induction by BARD1. A tumor-associated mutation Q564H of BARD1 is defective in apoptosis induction, thus suggesting a role of BARD1 in tumor suppression by mediating the signaling from proapoptotic stress toward induction of apoptosis. PMID- 11779502 TI - Structural studies of Ets-1/Pax5 complex formation on DNA. AB - Pax5 regulates the B cell-specific expression of the mb-1 gene together with members of the Ets family of transcriptional activators. The Ets proteins on their own bind poorly to the Pax5/Ets binding site, but can be recruited to the site by cooperative interactions with Pax5. The structure of the ETS domain of Ets-1 and the paired domain of Pax5 bound to DNA reveals the molecular details of the selective recruitment of different Ets proteins by Pax5. Comparison with structures of Ets-1 alone bound to both high- and low-affinity DNA sites reveals that Pax5 alters the Ets-1 contacts with DNA. The ability of one protein to alter the DNA sequence-specific contacts of another provides a general mechanism for combinatorial regulation of transcription. PMID- 11779503 TI - Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. AB - Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways. PMID- 11779504 TI - Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins. AB - Membrane-associated guanylate kinases (MAGUKs), such as PSD-95, are modular scaffolds that organize signaling complexes at synapses and other cell junctions. MAGUKs contain PDZ domains, which recruit signaling proteins, as well as a Src homology 3 (SH3) and a guanylate kinase-like (GK) domain, implicated in scaffold oligomerization. The crystal structure of the SH3-GK module from PSD-95 reveals that these domains form an integrated unit: the SH3 fold comprises noncontiguous sequence elements divided by a hinge region and the GK domain. These elements compose two subdomains that can assemble in either an intra- or intermolecular fashion to complete the SH3 fold. We propose a model for MAGUK oligomerization in which complementary SH3 subdomains associate by 3D domain swapping. This model provides a possible mechanism for ligand regulation of oligomerization. PMID- 11779505 TI - Structural basis of Smad1 activation by receptor kinase phosphorylation. AB - Phosphorylation of Smad1 at the conserved carboxyl terminal SVS sequence activates BMP signaling. Here we report the crystal structure of the Smad1 MH2 domain in a conformation that reveals the structural effects of phosphorylation and a molecular mechanism for activation. Within a trimeric subunit assembly, the SVS sequence docks near two putative phosphoserine binding pockets of the neighboring molecule, in a position ready to interact upon phosphorylation. The MH2 domain undergoes concerted conformational changes upon activation, which signal Smad1 dissociation from the receptor kinase for subsequent heteromeric assembly with Smad4. Biochemical and modeling studies reveal unique favorable interactions within the Smad1/Smad4 heteromeric interface, providing a structural basis for their association in signaling. PMID- 11779506 TI - Structural characterization of the intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95. AB - PSD-95/SAP90 is a member of the MAGUK superfamily. In excitatory synapses, PSD-95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules. We have determined the crystal structures of the apo and GMP-bound forms to 2.3 and 2.0 A resolutions, respectively, of a fragment containing the SH3, HOOK, and guanylate kinase (GK) domains of PSD-95. We observe an intramolecular interaction between the SH3 and GK domains involving the formation of a beta sheet including residues N- and C-terminal to the GK domain. Based on amino acid conservation and mutational data available in the literature, we propose that this intramolecular interaction is a common feature among MAGUK proteins. PMID- 11779507 TI - The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. AB - We show that Janus kinase 2 (JAK2), and more specifically just its intact N terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression. This interaction is specific as JAK1 has no effect. Residues 32 to 58 of the JAK2 JH7 domain are required for EpoR surface expression. Alanine scanning mutagenesis of the EpoR membrane proximal region reveals two modes of EpoR-JAK2 interaction. A continuous block of EpoR residues is required for functional, ligand-independent binding to JAK2 and cell surface receptor expression, whereas four specific residues are essential in switching on prebound JAK2 after ligand binding. Thus, in addition to its kinase activity required for cytokine receptor signaling, JAK is also an essential subunit required for surface expression of cytokine receptors. PMID- 11779508 TI - Proteins are unfolded on the surface of the ATPase ring before transport into the proteasome. AB - The 19S component of the 26S proteasome contains six ATPase subunits. To clarify how they unfold and translocate proteins into the 20S proteasome for degradation, we studied the homologous archaebacterial proteasome-regulatory ATPase complex PAN and the globular substrate GFP-SsrA. When we attached a small (Biotin) or large (Biotin-Avidin) moiety near its N terminus or a Biotin near its C terminus, GFP-SsrA was unfolded and degraded. However, attaching Avidin near its C terminus blocked passage through PAN and prevented GFP-SsrA degradation. Though not translocated, GFP-Avidin still underwent ATP-dependent unfolding. Moreover, it remained bound to PAN and inhibited further proteolysis. Therefore, (1) translocation and degradation of this substrate require threading through the ATPase in a C to N direction and (2) translocation does not cause but follows ATP dependent unfolding, which occurs on the surface of the ATPase ring. PMID- 11779509 TI - Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins. AB - SR proteins recognize exonic splicing enhancer (ESE) elements and promote exon use, whereas certain hnRNP proteins bind to exonic splicing silencer (ESS) elements and block exon recognition. We investigated how ESS3 in HIV-1 tat exon 3 blocks splicing promoted by one SR protein (SC35) but not another (SF2/ASF). hnRNP A1 mediates silencing by binding initially to a required high-affinity site in ESS3, which then promotes further hnRNP A1 association with the upstream region of the exon. Both SC35 and SF2/ASF recognize upstream ESE motifs, but only SF2/ASF prevents secondary hnRNP A1 binding, presumably by blocking its cooperative propagation along the exon. The differential antagonism between a negative and two positive regulators exemplifies how inclusion of an alternative exon can be modulated. PMID- 11779510 TI - The nucle(ol)ar Tif6p and Efl1p are required for a late cytoplasmic step of ribosome synthesis. AB - Deletion of elongation factor-like 1 (Efl1p), a cytoplasmic GTPase homologous to the ribosomal translocases EF-G/EF-2, results in nucle(ol)ar pre-rRNA processing and pre-60S subunits export defects. Efl1p interacts genetically with Tif6p, a nucle(ol)ar protein stably associated with pre-60S subunits and required for their synthesis and nuclear exit. In the absence of Efl1p, 50% of Tif6p is relocated to the cytoplasm. In vitro, the GTPase activity of Efl1p is stimulated by 60S, and Efl1p promotes the dissociation of Tif6p-60S complexes. We propose that Tif6p binds to the pre-60S subunits in the nucle(ol)us and escorts them to the cytoplasm where the GTPase activity of Efl1p triggers a late structural rearrangement, which facilitates the release of Tif6p and its recycling to the nucle(ol)us. PMID- 11779511 TI - Bacterial polypeptide release factor RF2 is structurally distinct from eukaryotic eRF1. AB - Bacterial release factor RF2 promotes termination of protein synthesis, specifically recognizing stop codons UAA or UGA. The crystal structure of Escherichia coli RF2 has been determined to a resolution of 1.8 A. RF2 is structurally distinct from its eukaryotic counterpart eRF1. The tripeptide SPF motif, thought to confer RF2 stop codon specificity, and the universally conserved GGQ motif, proposed to be involved with the peptidyl transferase center, are exposed in loops only 23 A apart, and the structure suggests that stop signal recognition is more complex than generally believed. PMID- 11779512 TI - Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs. AB - RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end joining (NHEJ) proteins then join the coding segments and join the RSs. In wild type cells, both full-length and truncated ("core") RAGs lead to accumulation of "hybrid" V(D)J joins, in which an RS is appended to a different coding sequence. We now show that while hybrid joins do not accumulate in NHEJ-deficient cells that express full-length RAGs, they do accumulate in NHEJ-deficient cells that express the core RAGS; like those catalyzed by core RAGs in vitro, however, they are sealed on just one DNA strand. These results suggest a potential role for the non-core regions in repressing potentially harmful transposition events. PMID- 11779513 TI - Benefits of immediate initiation of statin therapy following successful coronary stent implantation in patients with stable and unstable angina pectoris and Q wave acute myocardial infarction. AB - Statin therapy reduces clinical events in patients with stable coronary artery disease. Recent data indicate that the beneficial effects of statin therapy may also extend to patients experiencing an acute ischemic coronary event. However, the potential role of statins to further modify clinical outcome in patients undergoing coronary stent implantation has not been addressed. Therefore, we investigated whether the initiation of statin therapy immediately after successful coronary stent implantation improves short-term clinical outcome in 704 patients (335 patients with stable angina pectoris [AP], 224 patients with unstable AP, and 145 patients with Q-wave acute myocardial infarction [AMI]). Compared with the lowest risk group (patients with stable AP receiving statin therapy), patients with unstable AP (RR 6.9, 95% confidence interval [CI] 1.5 to 31, p = 0.004) and patients with Q-wave AMI (RR 7.6, 95% CI 1.5 to 37, p = 0.004) experienced an increased risk for the occurrence of the primary combined end point of cardiac death and AMI. Importantly, initiation of statin therapy abrogated the increased risk in patients with unstable AP to the level of patients with stable AP receiving statin therapy (RR 1.5, 95% CI 0.2 to 11, p = 0.7). In contrast, statin therapy did not affect the RR in patients with Q-wave AMI during 6-month follow-up (RR 7.9, 95% CI 1.6 to 39 vs RR 7.6, 95% CI 1.5 to 37, p = NS). The beneficial effects of statin therapy after successful coronary stent implantation in unstable AP were most prominent during the first 4 weeks after the ischemic episode. Statins appear to contribute to the rapid transformation of unstable coronary artery disease into a stable condition with a very low event rate over the forthcoming 6 months in patients with unstable AP undergoing successful coronary stent implantation. PMID- 11779514 TI - Usefulness of lipoprotein changes during acute coronary syndromes for predicting postdischarge lipoprotein levels. AB - The aim of our study was to evaluate the lipoprotein changes that occur during acute coronary events, and to determine the lipoprotein threshold levels that identify patients who require future statin therapy. Lipoprotein levels were measured at admission, at 6 hours, the morning after admission, before discharge, and 3 months after discharge in patients with myocardial infarction and unstable angina. Patients with myocardial infarction on thrombolytic therapy (n = 63) and patients with unstable angina (n = 33) had a decrease in low-density lipoprotein (LDL) cholesterol levels < or = 24 hours after admission (-12 +/- 20% and -6 +/- 23%, respectively), but these levels returned to baseline before discharge. In patients with myocardial infarction who did not receive thrombolytic therapy (n = 37), the decrease was more gradual and peaked before hospital discharge (-7 +/- 19%). There was good correlation between LDL cholesterol levels at admission and after discharge, especially in normotriglyceridemic patients. Over 90% of patients with LDL cholesterol > or = 125 mg/dl on the morning after admission were candidates for statin therapy after discharge. Thus, the need for future statin therapy can be predicted with fair reliability during the initial 24 hours after admission. However, elevated baseline triglyceride levels significantly affect these LDL cholesterol changes and complicate prediction of long-term lipoprotein levels. PMID- 11779515 TI - Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease. AB - It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels <303 micromol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 micromol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p < or = 0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p < or = 0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality-including diuretic use-elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD. PMID- 11779516 TI - Relation of antibiotic use to risk of myocardial infarction in the general population. AB - There are conflicting reports of an association between Chlamydia pneumoniae (C. pneumoniae) infection and coronary artery disease (CAD); randomized trials of antibiotics for the secondary prevention of CAD are currently underway. Physicians may be tempted to believe that their choice of antibiotic class in treating any infection may alter the risk of CAD. Our objective was to determine if the use of antibiotics with antichlamydial activity in the general population reduces the risk of myocardial infarction. A healthcare claims database with 354,258 patients with continuous health and pharmacy coverage for at least 2 years between January 1, 1991 and December 31, 1997 was used for the analyses. Hazard ratios were derived from proportional hazards models with time-dependent covariates, relating antibiotic prescription to first claim related to incident first myocardial infarction during the observation period, adjusting for previous CAD, age, sex, diabetes, hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. There were a total of 1,684,091 person-years of observation and 16,139 incident myocardial infarctions. The adjusted hazard ratios were 1.10 (95% confidence intervals [CI] 1.04 to 1.16) for macrolides, 1.20 (95% CI 1.13 to 1.26) for quinolones, 1.10 (95% CI 0.96 to 1.21) for cephalosporins, 1.00 (95% CI 0.96 to 1.06) for tetracyclines, 1.01 (95% CI 0.96 to 1.06) for penicillins, and 1.13 (95% CI 0.98 to 1.30) for trimetroprim-sulfamethoxazole. The hazard ratios for individual antibiotics with activity against C. pneumoniae within each group were similar. Use of antibiotics with activity against C. pneumoniae does not reduce the risk of myocardial infarction in the general population. PMID- 11779517 TI - Impact of daily life myocardial ischemia in patients with chronic reversible and irreversible myocardial dysfunction. AB - Repetitive myocardial ischemia during daily life has been suggested as the underlying mechanism of reversible myocardial dysfunction, which may progress into a hibernating state. Thirty-seven patients with ischemic cardiomyopathy (ejection fraction 35 +/- 7%) underwent positron emission tomography (N-13 ammonia and 18-F-fluoro-2-deoxy-glucose [FDG]) and exercise testing before coronary artery bypass grafting (CABG) and 48- hour ambulatory electrocardiographic monitoring to detect ischemia before CABG and 6 months postoperatively. Reversibility of regional myocardial dysfunction was detected by echocardiographic follow-up at 5 days, 2 months, and 6 months after the operation. Preoperatively, ischemic episodes during daily activities were more common (2 [25th to 75th percentiles 0 to 4] vs 0 episodes, p <0.01) and duration of ischemia longer (9 [25th to 75th percentiles 0 to 37] vs 0 [25th to 75th percentiles 0 to 1] minutes, p <0.02) in patients with reversible dysfunction (n = 15) than in patients with irreversible dysfunction (n = 22). The number of ischemic episodes per patient correlated with the numbers of reversibly dysfunctional segments (p = 0.003), viable segments as seen by positron emission tomography (p <0.05), and flow-metabolic mismatch segments (p <0.05). CABG eliminated ambulatory ischemic episodes in patients with reversible dysfunction (0 episodes, p <0.05 vs before CABG). Preoperatively, all patients with reversible dysfunction had a positive exercise test (14 of 15 patients), whereas daily life ischemia was present in 60% of patients. Reversibly dysfunctional segments in patients with ambulatory ischemia had faster recovery of function (15 of 28 patients vs 2 of 12 patients recovered at 5 days, p <0.05), higher FDG uptake (0.86 +/- 0.19% vs 0.71 +/- 0.24%, p <0.05) than in patients without ambulatory ischemia, whereas perfusion was similar (0.63 +/- 0.20 and 0.62 +/- 0.19 ml/g/min). Thus, exercise-induced myocardial ischemia is associated with reversibility of myocardial dysfunction, but not all patients with reversible ischemic cardiomyopathy have ischemic attacks during daily life. PMID- 11779519 TI - Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome. AB - Why adults with the Eisenmenger syndrome fare so much better than other patients with severe pulmonary hypertension is not known, but may be related to unique hemodynamics found only in these patients and in normal fetuses. We used echocardiography to evaluate ventricular morphology and function in 80 subjects: 45 cyanotic adults and 5 cyanotic adolescents with Eisenmenger syndrome, 10 infants with nonrestrictive ventricular septal defect and left-to-right shunt flow (pre-Eisenmenger phase), and 20 fetuses with structurally normal hearts. Cross-sectional morphology of the hearts was the same in all 4 groups with a flat ventricular septum throughout the cardiac cycle and equal thickness of the right and left ventricular free walls (regression slope 0.98, r = 0.97, p <0.0001). This morphology was the same in patients independent of age, defect type, and ventricular function. Right ventricular fractional area change was slightly inferior to that of the left ventricle but normal in most patients with Eisenmenger syndrome (0.47 +/- 0.14 vs 0.51 +/- 0.13, p <0.01). Overall, there was a highly significant linear relation between right and left ventricular function (r = 0.81, p <0.0001). The hearts of patients with Eisenmenger syndrome are more like normal fetal hearts than normal adult hearts. Because of the unique cardiovascular hemodynamics, regression of right ventricular wall thickness does not occur and is likely the reason that patients with Eisenmenger syndrome fare so much better than other adults with severe pulmonary hypertension. PMID- 11779518 TI - A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy. AB - Familial hypertrophic cardiomyopathy (HC) can be caused by mutations in 9 different genes encoding sarcomere proteins expressed in cardiac muscle. To date, only 13 different mutations in the cardiac troponin T (cTnT) gene have been reported to cause HC. Clinical characteristics and prognosis associated with mutations of this gene have not been well characterized owing to the small size and composition of affected families. The aim of this study was to determine the characteristic phenotype of patients with HC caused by a novel cTnT gene mutation, Lys273Glu. Two hundred Japanese probands with HC were screened for mutations in the cTnT gene. The Lys273Glu missense mutation was present in 9 persons from 2 unrelated pedigrees. They exhibited different cardiac morphologies: 1 had a dilated cardiomyopathy-like feature, 7 had left ventricular hypertrophy with normal left ventricular systolic function, and the 6 of them had asymmetric septal hypertrophy. A 1-year-old boy was not evaluated with echocardiography. The mean maximum wall thickness was 18.0 +/- 5.5 mm (range 8 to 24). There were 7 histories of sudden death in 1 of the 2 families. The Lys273Glu substitution in the cTnT gene shows a high degree of penetrance (100% in persons aged >20 years), a high incidence of sudden death, and a partial transition from hypertrophic to dilated cardiomyopathy. Because the location of a mutation appears to influence the development of a phenotype, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members. PMID- 11779520 TI - Predisposing conditions for atrial fibrillation in atrial septal defect with and without operative closure. AB - The aims of this study were to determine the prevalence and predisposing conditions for atrial fibrillation (AF) in adults with atrial septal defect (ASD) and to evaluate the influence of age at surgical repair. The study population consisted of 286 adults with ASD (mean age 39.5 +/- 19 years). All patients had >or = 1 follow-up visit and a Doppler echocardiographic study. One hundred ninety two of the patients underwent surgical closure 1 to 34 years before the study. Analyzed variables were entered into univariate (Mann-Whitney U) and multivariate (stepwise logistic regression) models to assess independent predictors for AF. The prevalence of AF was similar in surgically treated patients (15.6%) and in the nonsurgical group (13.8%) (p = 0.69). Multivariate analysis showed that current age (RR 1.9 per each decade of age, 95% confidence interval [CI] 1.3 to 2.7, p = 0.001), mitral regurgitation (RR 3.0 per each degree of regurgitation, 95% CI 1.6 to 5.8, p = 0.001), left atrial enlargement (RR 2.8 per each 10 mm increase in size, 95% CI 1.5 to 5.2, p = 0.001), and tricuspid regurgitation (RR 1.9 per each degree of regurgitation, 95% CI 1.0 to 3.7, p = 0.04) were independent predictors of AF; however, gender, anatomic type, defect size, Qp:Qs, pulmonary artery pressure, right ventricular dimension, left ventricular shortening fraction, and prior surgical repair were not related to late AF development. In the surgical group, age >25 years at the time of surgery was the only predictor for AF independent of age at the time of the study (p = 0.02). PMID- 11779521 TI - Significant reduction of radiation exposure to operator and staff during cardiac interventions by analysis of radiation leakage and improved lead shielding. AB - The objectives of this study were to disclose and to reduce occupational radiation leakage in invasive cardiology. Prospectively, we analyzed various dose parameters for 330 coronary procedures. We used a Rando phantom to measure scatter entrance skin air kerma to the operator (S-ESAK-O) during fluoroscopy for all standard tube angulations, and to plot isodose lines for 0 degrees /0 degrees -posterior anterior angulation. The patient's measured dose area product due to diagnostic catheterization and elective percutaneous transluminal coronary angioplasty was 6.2 and 10.4 Gycm(2), which represents 11% and 13% of currently typical values, respectively. With use of 0.5- and 1.0-mm overcouch and undercouch shielding, it was possible to reduce the mean of 4,686 nSv/Gycm(2) to 677 and 277 nSv/Gycm(2), respectively. Closure of radiation leakage up to 897 microSv/hour at the operator's gonadal height (80 to 105 cm), not heretofore described, was achieved by an additional 1.0-mm, lead-equivalent undercouch-top and overcouch-flap adjacent to the table, down to a S-ESAK-O/dose area product level of 47.5 nSv/Gycm(2). With use of a 0.5-mm lead apron, collar, glasses, foot switch shield and 1.0-mm lead cover around the patient's thighs, the operator received a mean S-ESAK-O of 8.5, while his forehead, eyes, thyroid, chest, gonads, and hands were exposed to 68.2, 1.2, 1.2, 1.2, 0.8, and 58.2 nSv/Gycm(2), respectively. In conclusion, radiation-attenuating intervention techniques and improved lead protection can effectively contribute to a new state of the art in invasive cardiology, with reduction of operator radiation exposure to 0.8% of typical S-ESAK-O levels in advanced catheterization laboratories. PMID- 11779522 TI - Heart rate variability in healthy newborn infants. AB - In adults and older children, heart rate variability (HRV) is frequently used to study autonomic function noninvasively. Normal values of HRV in newborn infants, however, are not widely available. This problem may be partially attributed to the lack of standardization of different methods. This study assessed HRV in normal newborn infants using 24-hour Holter monitoring. From 1997 to 2000, we prospectively evaluated frequency- (spectral analysis), geometric-, and time domain indexes of HRV in normal term infants. Ninety-six asymptomatic infants who were <72 hours old were studied. Frequency-domain parameters (power in the high, low, very low, ultra low, and total frequency domains), a geometric parameter (HRV triangular index), and time-domain parameters (SDNN, SDANN, SDNNi, r-MSSD, s NN50) are reported as means +/- SD, medians, and 5th and 95th percentiles to establish the normative values for newborns. A high degree of correlation (r > or = 0.85, p <0.0001) was noted among the 3 vagal tone dependent parameters, such as high-frequency power (frequency domain), r-MSSD, and s-NN50 (time domain). Our study supports the use of vagal dependent time-domain parameters like r-MSSD and sNN50 as surrogates for high-frequency power in newborns. Because the data are reported as means +/- SD, medians, and 5th and 95th percentiles, their use facilitates the study of parasympathetic and sympathetic activity in comparable populations. PMID- 11779523 TI - Comparison of outcomes after percutaneous coronary revascularization with stents in patients with and without mild chronic renal insufficiency. PMID- 11779524 TI - Comparative analysis of stent placement versus balloon angioplasty in small coronary arteries with long narrowings (the Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small Arteries [ISAR-SMART] Trial). PMID- 11779525 TI - In-hospital costs of coronary stent implantation with and without eptifibatide (the ESPRIT Trial). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin. PMID- 11779526 TI - Usefulness of plasma N-terminal proatrial natriuretic peptide (proANP) as an early predictor of outcome in unstable angina pectoris or non-ST-elevation acute myocardial infarction. PMID- 11779527 TI - Incidence of new coronary events in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. PMID- 11779528 TI - Risk factors for acute myocardial infarction in the elderly (the Dubbo study). PMID- 11779529 TI - Impact of smoking on the incidence and survival of cardiogenic shock complicating acute myocardial infarction treated with reperfusion therapy. PMID- 11779530 TI - Evaluation of advanced electrocardiographic diagnostic software for detection of prior myocardial infarction. PMID- 11779531 TI - T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. PMID- 11779532 TI - Predictors of unsuccessful electrical cardioversion in atrial fibrillation. PMID- 11779533 TI - Effect of weight loss in congestive heart failure from idiopathic dilated cardiomyopathy on electrocardiographic QRS voltage. PMID- 11779534 TI - Factors leading to aortic valve replacement after previous cardiac surgery. PMID- 11779535 TI - Changes in protein distribution of the aortic wall following balloon aortoplasty for coarctation. PMID- 11779536 TI - Coronary artery anatomy in complete transposition of the great arteries with situs inversus. PMID- 11779537 TI - Effect of superior cavopulmonary anastomosis on the rate of tricuspid annulus dilation in hypoplastic left heart syndrome. PMID- 11779538 TI - Three-dimensional echocardiography of the right atrial embryonic remnants. PMID- 11779539 TI - Elevation of matrix metalloproteinase-2 level in pericardial fluid is closely associated with left ventricular remodeling. PMID- 11779540 TI - Large pleural effusions producing signs of cardiac tamponade resolved by thoracentesis. PMID- 11779541 TI - Heart rate and blood pressure turbulence--marker of the baroreflex sensitivity or consequence of postextrasystolic potentiation and pulsus alternans? PMID- 11779542 TI - Effect of fenofibrate on Chlamydia pneumoniae antibody levels in patients with coronary artery disease. PMID- 11779543 TI - Why use double balloon if single Inoue balloon will do for percutaneous balloon mitral valvuloplasty? PMID- 11779544 TI - Potential intervention for depression associated with increased mortality risk in patients after myocardial infarction. PMID- 11779545 TI - Coronary flow reserve or brachial artery flow to assess endothelial dysfunction: is it time to look at the heart again? PMID- 11779547 TI - Ultrafast haem-haem electron transfer in cytochrome c oxidase. AB - Electron transfer between the redox centres is essential for the function of the haem-copper oxidases. To date, the fastest rate of electron transfer between the haem groups has been determined to be ca. 3 x 10(5) s(-1). Here, we show by optical spectroscopy that about one half of this electron transfer actually occurs at least three orders of magnitude faster, after photolysis of carbon monoxide from the half-reduced bovine heart enzyme. We ascribe this to the true haem-haem electron tunnelling rate between the haem groups. PMID- 11779548 TI - Comparative genomics and bioenergetics. AB - Bacterial and archaeal complete genome sequences have been obtained from a wide range of evolutionary lines, which allows some general conclusions about the phylogenetic distribution and evolution of bioenergetic pathways to be drawn. In particular, I searched in the complete genomes for key enzymes involved in aerobic and anaerobic respiratory pathways and in photosynthesis, and mapped them into an rRNA tree of sequenced species. The phylogenetic distribution of these enzymes is very irregular, and clearly shows the diverse strategies of energy conservation used by prokaryotes. In addition, a thorough phylogenetic analysis of other bioenergetic protein families of wide distribution reveals a complex evolutionary history for the respective genes. A parsimonious explanation for these complex phylogenetic patterns and for the irregular distribution of metabolic pathways is that the last common ancestor of Bacteria and Archaea contained several members of every gene family as a consequence of previous gene or genome duplications, while different patterns of gene loss occurred during the evolution of every gene family. This would imply that the last universal ancestor was a bioenergetically sophisticated organism. Finally, important steps that occurred during the evolution of energetic machineries, such as the early evolution of aerobic respiration and the acquisition of eukaryotic mitochondria from a proteobacterium ancestor, are supported by the analysis of the complete genome sequences. PMID- 11779549 TI - Properties of a proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli with alpha and beta subunits linked through fused transmembrane helices. AB - Proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli is composed of an alpha and a beta subunit, whereas the homologues mitochondrial enzyme contains a single polypeptide. As compared to the latter transhydrogenase, using a 14-helix model for its membrane topology, the point of fusion is between the transmembrane helices 4 and 6 where the fusion linker provides the extra transmembrane helix 5. In order to clarify the potential role of this extra helix/linker, the alpha and the beta subunits were fused using three connecting peptides of different lengths, one (pAX9) involving essentially a direct coupling, a second (pKM) with a linking peptide of 18 residues, and a third (pKMII) with a linking peptide of 32 residues, as compared to the mitochondrial extra peptide of 27 residues. The results demonstrate that the plasma membrane-bound and purified pAX9 enzyme with the short linker was partly misfolded and strongly inhibited with regard to both catalytic activities and proton translocation, whereas the properties of pKM and pKMII with longer linkers were similar to those of wild-type E. coli transhydrogenase but partly different from those of the mitochondrial enzyme although pKMII generally gave higher activities. It is concluded that a mitochondrial-like linking peptide is required for proper folding and activity of the E. coli fused transhydrogenase, and that differences between the catalytic properties of the E. coli and the mitochondrial enzymes are unrelated to the linking peptide. This is the first time that larger subunits of a membrane protein with multiple transmembrane helices have been fused with retained activity. PMID- 11779550 TI - The osmolality of the cell suspension regulates phycobilisome-to-photosystem I excitation transfers in cyanobacteria. AB - The chlorophyll a (Chla) fluorescence of cyanobacteria, which at physiological temperature originates from photosystem (PS) II holochromes, is suppressed in hyperosmotic suspension, and enhanced in hypo-osmotic suspension (G.C. Papageorgiou, A. Alygizaki-Zorba, Biochim. Biophys. Acta 1335 (1997) 1-4). We investigated the mechanism of this phenomenon by comparing Synechococcus sp. PCC 7942 cells that had been treated with N-ethylmaleimide (NEM) in order to inhibit electronic excitation transfers from phycobilisomes (PBS) to Chlas of PSI (A.N. Glazer, Y.M. Gindt, C.F. Chan, K. Sauer, Photosynth. Res. 40 (1994) 167-173) with untreated control cells. The NEM-treated cells were indistinguishable from the control cells with regard to PSII-dependent oxygen evolution, reduction of post PSII oxidants, and osmotically induced volume changes, but differed in the following properties: (i) they could not photoreduce post-PSI electron acceptors; (ii) they diverted more PBS excitation to PSII; (iii) the rise of Chla fluorescence upon light acclimation of darkened (state 2) cells was smaller; and (iv) the Chla fluorescence of light-acclimated (state 1) cells was insensitive to the cell suspension osmolality. These properties suggest that osmolality regulates the core-mediated excitation coupling between PBS and PSI, possibly by influencing mutual orientation and/or distance between core holochromes (ApcE, ApcD) and PSI holochromes. Thus, in hyper-osmotic suspension, PBS deliver more excitation to PSI (hence less to PSII); in hypo-osmotic cell suspension they deliver less excitation to PSI (hence more to PSII). PMID- 11779551 TI - The presence of 9-cis-beta-carotene in cytochrome b(6)f complex from spinach. AB - Cytochrome b(6)f complex with stoichiometrically bound beta-carotene molecule was purified from spinach chloroplasts. The configuration of this beta-carotene was studied by reversed-phase HPLC and resonance Raman spectroscopy. Both the absorption spectrum of this beta-carotene in dissociated state and the Raman spectrum in native state can be unambiguously assigned to a 9-cis configuration. This finding is in contrast to the predominantly all-trans isomers commonly found in membranes and protein-pigment complexes of chloroplasts, suggesting that the 9 cis-beta-carotene is an authentic component and may have a unique structural and functional role in cytochrome b(6)f complex. PMID- 11779552 TI - Coupling of proton flow to ATP synthesis in Rhodobacter capsulatus: F(0)F(1)-ATP synthase is absent from about half of chromatophores. AB - F(0)F(1)-ATP synthase (H(+)-ATP synthase, F(0)F(1)) utilizes the transmembrane protonmotive force to catalyze the formation of ATP from ADP and inorganic phosphate (P(i)). Structurally the enzyme consists of a membrane-embedded proton translocating F(0) portion and a protruding hydrophilic F(1) part that catalyzes the synthesis of ATP. In photosynthetic purple bacteria a single turnover of the photosynthetic reaction centers (driven by a short saturating flash of light) generates protonmotive force that is sufficiently large to drive ATP synthesis. Using isolated chromatophore vesicles of Rhodobacter capsulatus, we monitored the flash induced ATP synthesis (by chemoluminescence of luciferin/luciferase) in parallel to the transmembrane charge transfer through F(0)F(1) (by following the decay of electrochromic bandshifts of intrinsic carotenoids). With the help of specific inhibitors of F(1) (efrapeptin) and of F(0) (venturicidin), we decomposed the kinetics of the total proton flow through F(0)F(1) into (i) those coupled to the ATP synthesis and (ii) the de-coupled proton escape through F(0). Taking the coupled proton flow, we calculated the H(+)/ATP ratio; it was found to be 3.3+/-0.6 at a large driving force (after one saturating flash of light) but to increase up to 5.1+/-0.9 at a smaller driving force (after a half-saturating flash). From the results obtained, we conclude that our routine chromatophore preparations contained three subsets of chromatophore vesicles. Chromatophores with coupled F(0)F(1) dominated in fresh material. Freezing/thawing or pre illumination in the absence of ADP and P(i) led to an increase in the fraction of chromatophores with at least one de-coupled F(0)(F(1)). The disclosed fraction of chromatophores that lacked proton-conducting F(0)(F(1)) (approx. 40% of the total amount) remained constant upon these treatments. PMID- 11779553 TI - Endothelial- and nitric oxide-dependent effects on oxidative metabolism of intact artery. AB - Oxidative metabolism and its possible modulation by nitric oxide (NO) was examined in endothelial-intact and endothelial-denuded segments of porcine carotid arteries. Endothelial-intact arteries displayed appropriate NO-mediated vasorelaxation to acetylcholine (ACh). Endothelial-denuded arteries demonstrated absent vasorelaxation to ACh stimulation and depressed contractile responsiveness to K(+) depolarization, which was normalized by inhibition of NO synthesis by N(omega)-nitro-L-arginine methylester (L-NAME). Confirmation that carotid arteries continued to produce NO despite removal of the endothelium was indicated by detection of NO metabolites in the incubation medium bathing the arteries. O(2) consumption and the oxidation of glucose and fatty acid were depressed in endothelial-denuded arteries. Depression of O(2) consumption and glucose oxidation was completely reversed by treatment with L-NAME. We conclude that endogenous NO produced by non-endothelial vascular cells depresses contractility, O(2) consumption, and oxidation of energy substrates in vascular smooth muscle. The endothelium may play a role in oxidative metabolism of vascular smooth muscle possibly by modulating the effects of NO produced by other cells of the vessel wall, or by other factors. PMID- 11779554 TI - Expression of sodium/proton antiporter NhaA at various pH values in Escherichia coli. AB - It was reported that NhaA, one of sodium/proton antiporters in Escherichia coli, was expressed at alkaline pH [J. Biol. Chem. 266 (1991) 21753]. In disagreement with their results, expression of an nhaA-lacZ fusion gene was found to be very low in an E. coli strain derived from MC4100 within the wide pH range from 5 to 9. When nhaB was deleted, the fusion gene was expressed at pH values below 8, while the expression was observed at alkaline pH after chaA was deleted. The internal level of sodium ions was increased by deletion of nhaA in strains deficient in nhaB and chaA at low and high pH values, respectively. These results suggested that nhaA is induced only when a low level of internal sodium ions is not kept by NhaB and ChaA. Strains used in the previous study may have low active ChaA. PMID- 11779555 TI - Effect of deuterium oxide on actomyosin motility in vitro. AB - Actin filament velocities in an in vitro motility assay system were measured both in heavy water (deuterium oxide, D(2)O) and water (H(2)O) to examine the effect of D(2)O on the actomyosin interaction. The dependence of the sliding velocity on pD of the D(2)O assay solution showed a broad pD optimum of around pD 8.5 which resembled the broad pH optimum (pH 8.5) of the H(2)O assay solution, but the maximum velocity (4.1+/-0.5 microm/s, n=11) at pD 8.5 in D(2)O was about 60% of that (7.1+/-1.1 microm/s, n=11) at pH 8.5 in H(2)O. The K(m) values of 95 and 80 microM and V(max) values of 3.2 and 5.1 microm/s for the D(2)O and H(2)O assay were obtained by fitting the ATP concentration dependence of the velocity (at pD and pH 7.5) to the Michaelis-Menten equation. The K(m) value of actin-activated Mg-ATPase activity of myosin subfragment 1 (S1) was decreased from 50 microM [actin] in H(2)O to 33 microM [actin] in D(2)O without any significant changes in V(max) (9.4 s(-1) in D(2)O and 9.3 s(-1) in H(2)O). The rate constants of ADP release from the acto-S1-ADP complex measured by the stopped flow method were 361+/-26 s(-1) (n=27) in D(2)O and 512+/-39 s(-1) (n=27) in H(2)O at 6 degrees C. These results suggest that the decrease in the in vitro actin-myosin sliding velocity in D(2)O results from a slowing of the release of ADP from the actomyosin-ADP complex and the increase in the affinity of actin for myosin in the presence of ATP in D(2)O. PMID- 11779556 TI - Photosynthetic water oxidation in Synechocystis sp. PCC6803: mutations D1-E189K, R and Q are without influence on electron transfer at the donor side of photosystem II. AB - The oxygen-evolving manganese cluster (OEC) of photosynthesis is oxidised by the photochemically generated primary oxidant (P(+*)(680)) of photosystem II via a tyrosine residue (Y(Z), Tyr161 on the D1 subunit of Synechocystis sp. PCC6803). The redox span between these components is rather small and probably tuned by protonic equilibria. The very efficient electron transfer from Y(Z) to P(+*)(680) in nanoseconds requires the intactness of a hydrogen bonded network involving Y(Z), D1-His190, and presumably D1-Glu189. We studied photosystem II core particles from photoautotrophic mutants where the residue D1-E189 was replaced by glutamine, arginine and lysine which were expected to electrostatically differ from the glutamate in the wild-type (WT). Surprisingly, the rates of electron transfer from Y(Z) to P(+*)(680) as well as from the OEC to Y(ox)(Z) were the same as in the WT. With the generally assumed proximity between D1-His190 (and thus D1-Glu189) and Y(Z), the lack of any influence on the electron transfer around Y(Z) straightforwardly implies a strongly hydrophobic environment forcing Glu (acid) and Lys, Arg (basic) at position D1-189 into electro-neutrality. As one alternative, D1-Glu189 could be located at such a large distance from the OEC, Y(Z) and P(+*)(680) that a charge on D1-189X does not influence the electron transfer. This seems less likely in the light of the drastic influence of its direct neighbour, D1-His190, on Y(Z) function. Another alternative is that D1 Glu189 is negatively charged, but is located in a cluster of acid/base groups that compensates for an alteration of charge at position 189, leaving the overall net charge unchanged in the Gln, Lys, and Arg mutants. PMID- 11779557 TI - Inhibition of steady-state mitochondrial ATP synthesis by bicarbonate, an activating anion of ATP hydrolysis. AB - Bicarbonate, an activating anion of ATP hydrolysis, inhibited ATP synthesis coupled to succinate oxidation in beef heart submitochondrial particles but diminished the lag time and increased the steady-state velocity of the (32)Pi-ATP exchange reaction. The latter effects exclude the possibility that bicarbonate is inducing an intrinsic uncoupling between ATP hydrolysis and proton translocation at the level of F(1)F(o) ATPase. The inhibition of ATP synthesis was competitive with respect to ADP at low fixed [Pi], mixed at high [Pi] and non-competitive towards Pi at any fixed [ADP]. From these results we can conclude that (i) bicarbonate does not bind to a Pi site in the mitochondrial F(1); (ii) it competes with the binding of ADP to a low-affinity site, likely the low-affinity non-catalytic nucleotide binding site. It is postulated that bicarbonate stimulates ATP hydrolysis and inhibits ATP synthesis by modulating the relative affinities of the catalytic site for ATP and ADP. PMID- 11779558 TI - Involvement of zeaxanthin and of the Cbr protein in the repair of photosystem II from photoinhibition in the green alga Dunaliella salina. AB - A light-sensitive and chlorophyll (Chl)-deficient mutant of the green alga Dunaliella salina (dcd1) showed an amplified response to irradiance stress compared to the wild-type. The mutant was yellow-green under low light (100 micromol photons m(-2) s(-1)) and yellow under high irradiance (2000 micromol photons m(-2) s(-1)). The mutant had lower levels of Chl, lower levels of light harvesting complex II, and a smaller Chl antenna size. The mutant contained proportionately greater amounts of photodamaged photosystem (PS) II reaction centers in its thylakoid membranes, suggesting a greater susceptibility to photoinhibition. This phenotype was more pronounced under high than low irradiance. The Cbr protein, known to accumulate when D. salina is exposed to irradiance stress, was pronouncedly expressed in the mutant even under low irradiance. This positively correlated with a higher zeaxanthin content in the mutant. Cbr protein accumulation, xanthophyll cycle de-epoxidation state, and fraction of photodamaged PSII reaction centers in the thylakoid membrane showed a linear dependence on the chloroplast 'photoinhibition index', suggesting a cause and-effect relationship between photoinhibition, Cbr protein accumulation and xanthophyll cycle de-epoxidation state. These results raised the possibility of zeaxanthin and Cbr involvement in the PSII repair process through photoprotection of the partially disassembled, and presumably vulnerable, PSII core complexes from potentially irreversible photooxidative bleaching. PMID- 11779559 TI - Evaluation of the energetic position of the lowest excited singlet state of beta carotene by NEXAFS and photoemission spectroscopy. AB - In carotenoids the lowest energetic optical transition belonging to the pi electron system is forbidden by symmetry, therefore the energetic position of the S(1) (2(1)A(g)) level can hardly be assessed by optical spectroscopy. We introduce a novel experimental approach: For molecules with pi-electron systems the transition C1s-->2p(pi*) from inner-atomic to the lowest unoccupied molecular orbital (LUMO) appears in X-ray absorption near edge spectra (NEXAFS) as an intense, sharp peak a few eV below the carbon K-edge. Whereas the peak position reflects the energy of the first excited singlet state in relation to the ionization potential of the molecule, intensity and width of the transition depend on hybridization and bonding partners of the selected atom. Complementary information can be obtained from ultraviolet photoelectron spectroscopy (UPS): At the low binding energy site of the spectrum a peak related to the highest occupied molecular orbital (HOMO) appears. We have measured NEXAFS and UPS of beta-carotene. Based on these measurements and quantum chemical calculations the HOMO and LUMO energies can be derived. PMID- 11779560 TI - Interactions of the drug amphotericin B with phospholipid membranes containing or not ergosterol: new insight into the role of ergosterol. AB - Amphotericin B (AmB) is an amphipathic polyene antibiotic which permeabilizes ergosterol-containing membranes, supposedly by formation of pores. In water, AmB forms chiral aggregates, modelled as stacks of planar dimers in which the joined polyene chains in each dimer turn round, from one dimer to the following in these stacks, by forming a helical array. Studies of the binding of AmB with L dipalmitoylphosphatidylcholine (L-DPPC) and L-dilauroylphosphatidylcholine (L DLPC) bilayers disclose the main following results. (1) An inversion of the helicity of the L-DPPC-bound AmB aggregates, when the L-DPPC bilayers are in the gel phase, is inferred from the evolution of the circular dichroism spectra of AmB+L-DPPC mixtures. (2) An AmB-induced gel-to-subgel transformation of L-DPPC bilayers, in the previous mixtures, is revealed by a differential scanning calorimetry study. (3) The role played by ergosterol in the location of phospholipid-bound AmB aggregates with respect to a phospholipid bilayer is directly demonstrated from atomic force microscopy observations of mica-supported AmB+L-DLPC mixtures, in the presence or absence of ergosterol. While in the absence of ergosterol AmB aggregates remained at the surface of the bilayer, in the presence of ergosterol they appeared embedded within this bilayer and became hollow-centered. As such an embedding in the hydrophobic core of a bilayer requires a rearrangement of the aggregates with respect to their architecture in water, this rearrangement is held responsible for the hollowing of aggregates. The hollow-centered sublayer-embedded AmB aggregates are thought to be the precursors of the formation of AmB pores. PMID- 11779561 TI - Low-affinity potassium uptake by Saccharomyces cerevisiae is mediated by NSC1, a calcium-blocked non-specific cation channel. AB - Previous descriptions by whole-cell patch clamping of the calcium-inhibited non selective cation channel (NSC1) in the plasma membrane of Saccharomyces cerevisiae (H. Bihler, C.L. Slayman, A. Bertl, FEBS Lett. 432 (1998); S.K. Roberts, M. Fischer, G.K. Dixon, D.Sanders, J. Bacteriol. 181 (1999)) suggested that this inwardly rectifying pathway could relieve the growth inhibition normally imposed on yeast by disruption of its potassium transporters, Trk1p and Trk2p. Now, demonstration of multiple parallel effects produced by various agonists and antagonists on both NSC1 currents and growth (of trk1 Delta trk2 Delta strains), has identified this non-selective cation pathway as the primary low-affinity uptake route for potassium ions in yeast. Factors which suppress NSC1-mediated inward currents and inhibit growth of trk1 Delta trk2 Delta cells include (i) elevating extracellular calcium over the range of 10 microM-10 mM, (ii) lowering extracellular pH over the range 7.5-4, (iii) blockade of NSC1 by hygromycin B, and (iv) to a lesser extent by TEA(+). Growth of trk1 Delta trk2 Delta cells is also inhibited by lithium and ammonium; however, these ions do not inhibit NSC1, but instead enter yeast cells via NSC1. Growth inhibition by lithium ions is probably a toxic effect, whereas growth inhibition by ammonium ions probably results from competitive inhibition, i.e. displacement of intracellular potassium by entering ammonium. PMID- 11779562 TI - Kinetics of erythrocyte swelling and membrane hole formation in hypotonic media. AB - Red blood cell (RBC) swelling and membrane hole formation in hypotonic external media were studied by measuring the time-dependent capacitance, C, and the conductance, G, in the beginning of the beta-dispersion range. At high and moderate osmolarities of the external solution the capacitance reaches a steady state whereas at low osmolarities it reveals a biphasic kinetics. Examination of RBC suspensions exposed to different concentrations of HgCl(2) demonstrates that water transport through mercury-sensitive water channel controls RBC swelling. Unlike the capacitance, an increase in the conductance to a stationary level is observed after a certain delay. A comparison of G(t) curves recorded for the suspensions of the intact cells and those treated with cytochalasin B or glutaraldehyde demonstrates the significant effect of the membrane viscoelasticity on the pore formation. It is shown that the stretched membrane of completely swollen RBC retains its integrity for a certain time, termed as the membrane lifetime, t(memb). Therefore, the resistivity of RBCs to a certain osmotic shock may be quantified by the distribution function of RBC(t(memb)). PMID- 11779563 TI - Calmodulin antagonists do not inhibit IK(Ca) channels of human erythrocytes. AB - Patch-clamp recordings were performed to study the effects of three calmodulin (CaM) antagonists on the gating of intermediate calcium-activated K(+) channels (IK(Ca)) of human erythrocytes. In the cell-attached configuration, both opening frequency and open probability of IK(Ca) channels were not significantly different in control cells and in those incubated with calmidazolium, trifluoperazine or W7. IK(Ca) channels in excised membrane patches, were normally activated by the calcium bathing the cytoplasmic side in the presence of CaM antagonists, at calcium concentrations ranging from 10(-7) to 10(-3) M. The activity of IK(Ca) channels, which had been previously up-modulated by an endogenous cAMP-dependent protein kinase, was not inhibited when perfused with CaM antagonists. The results presented in this study demonstrate that calmodulin antagonists do not inhibit the activity of native IK(Ca) channels of human erythrocytes. These data are in accordance with findings on the cloned IK(Ca) indicating that calmodulin is constitutively associated with these channels. PMID- 11779564 TI - Human erythroid cells are affected by aluminium. Alteration of membrane band 3 protein. AB - There is evidence that anaemia is associated with aluminium (Al). We have already reported on the sensitivity to Al, showed by erythroid cell populations of animals chronically exposed to the metal. In order to investigate whether Al could also affect human cells, experiments were carried out both on immature and mature human erythroid cells. Erythroid progenitors (CFU-E, colony-forming units erythroid) concentrated from human peripheral blood were cultured in an Al-rich medium under erythropoietin stimulation and their development analysed. Human peripheral erythrocytes were aged in the presence of Al. Cells were examined using scanning electron microscopy, and membrane proteins analysed by polyacrylamide gel electrophoresis with sodium dodecyl sulphate and immunoblotting. The development of the Al-treated progenitors was 8750/6600-9200 CFU-E/10(6) cells, a significantly lower median value (P<0.05) than that showed by non-treated cells (12300/11200-20700 CFU-E/10(6) cells). Erythrocyte morphological changes were induced by Al during the in vitro ageing. The cells lost their typical biconcave shape, turning into acanthocytes and stomatocytes. Simultaneously, an increased membrane protein breakdown compatible with band 3 degradation was detected. Besides, Al was found within the cells and attached to the membrane. The present in vitro results suggest that Al may disturb human erythropoiesis through combined effects on mature erythrocytes and cellular metabolism in late erythroid progenitors. PMID- 11779565 TI - Substituted aniline interaction with submitochondrial particles and quantitative structure-activity relationships. AB - The toxic effects of eighteen substituted anilines were determined by means of a short-term in vitro assay, using submitochondrial particles (SMP) as biosensors. The assay allows for the quantification of the effects of toxicants that act specifically on mitochondrial respiratory functions, like uncouplers and inhibitors, or non-specifically, by disturbing the structure and functioning of the inner mitochondrial membrane. The obtained EC(50) values range from 72.5 to 1910 micromol/l. The type and position of the substituents are of fundamental importance in determining the toxic potency. In general, the presence of electron withdrawing substituents produces higher toxic effects, whereas electron-donating groups seem to reduce the toxicity. Quantitative structure-activity relationships (QSAR) showed that toxicity values were correlated with the Hammett sigma constant and with hydrogen bonding capacity descriptors, such as E(LUMO), E(HOMO) and Q(+). The results indicate that toxicity increases with increasing the hydrogen bonding donor capacity of the NH(2) group and support the hypothesis of a mechanism of action based on hydrogen bonding formation between the amino group of anilines and polar groups at the membrane/water interface. Such an interaction would cause a derangement of the membrane structure and, as a consequence, a disturbance of its functioning. PMID- 11779566 TI - The mycocidal, membrane-active complex of Cryptococcus humicola is a new type of cellobiose lipid with detergent features. AB - The chemical composition of the mycocidal complex (formerly known as microcin) secreted by Cryptococcus humicola was investigated by chemical, mass spectrometric and nuclear magnetic resonance methods. The results indicate that the mycocidal complex is composed of glycolipids with a highly acetylated (up to five acetyl groups) cellobiose backbone [beta-D-Glcp-(1'-->4)-beta-D-Glcp] linked to the omega-hydroxyl group of alpha,omega-dihydroxy palmitate [16:0-alpha,omega di-OH] with an unsubstituted carboxyl group. The acyl chain forming aglycon can be replaced by [18:0-(alpha,omega-di-OH)], [18:0-(alpha,omega-1,omega-tri-OH)], and [18:0-(alpha,omega-2,omega-tri-OH)]. The complex has a comparatively high surface activity; 0.5 mg/ml of it reduced the surface tension of 0.1 M NaHCO(3) from 71 mN/m to 37 mN/m and interfacial tension against n-hexadecane from 39 mN/m to 10 mN/m. The critical micelle concentration of the complex at pH 4.0, determined by the fluorometric method with N-phenyl-1-naphthylamine as fluorescent probe and by the De Nouy ring method, was 2 x 10(-5) M (taking the average molecular mass of the complex to be 750); it did not depend on the presence of 100 mM KCl and was an order of magnitude higher at pH 7.0. By fluorescence resonance energy transfer spectroscopy with N-(7-nitro-2,1,3 benzoxadiazol-4-yl)-phosphatidylethanolamine as energy donor and N-(rhodamine B sulfonyl)-phosphatidylethanolamine as energy acceptor the complex was shown to intercalate into the liposomal lipid matrix. Primary lesions caused by the complex in planar lipid bilayers were revealed as short-living current fluctuations of a broad spectrum of amplitudes. The mycocidal effect of the complex is suggested to be associated with its detergent-like properties. PMID- 11779567 TI - General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides. AB - Model compounds of modified hydrophobicity (Eta), hydrophobic moment (mu) and angle subtended by charged residues (Phi) were synthesized to define the general roles of structural motifs of cationic helical peptides for membrane activity and selectivity. The peptide sets were based on a highly hydrophobic, non-selective KLA model peptide with high antimicrobial and hemolytic activity. Variation of the investigated parameters was found to be a suitable method for modifying peptide selectivity towards either neutral or highly negatively charged lipid bilayers. Eta and mu influenced selectivity preferentially via modification of activity on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) bilayers, while the size of the polar/hydrophobic angle affected the activity against 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol (POPG). The influence of the parameters on the activity determining step was modest in both lipid systems and the activity profiles were the result of the parameters' influence on the second less pronounced permeabilization step. Thus, the activity towards POPC vesicles was determined by the high permeabilizing efficiency, however, changes in the structural parameters preferentially influenced the relatively moderate affinity. In contrast, intensive peptide accumulation via electrostatic interactions was sufficient for the destabilization of highly negatively charged POPG lipid membranes, but changes in the activity profile, as revealed by the modification of Phi, seem to be preferentially caused by variation of the low permeabilizing efficiency. The parameters proved very effective also in modifying antimicrobial and hemolytic activity. However, their influence on cell selectivity was limited. A threshold value of hydrophobicity seems to exist which restricted the activity modifying potential of mu and Phi on both lipid bilayers and cell membranes. PMID- 11779568 TI - Molecular characteristics of small intestinal and renal brush border thiamin transporters in rats. AB - The molecular characteristics of thiamin (T) transport were studied in the small intestinal and renal brush border membrane vesicles of rats, using [(3)H]T at high specific activity. The effects of various chemical modifiers (amino acid blockers) on T uptake were examined and their specificity assessed. Treatment with the carboxylic specific blockers 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate, (1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride and N-ethyl-5-phenylisoaxolium-3'-sulfonate (Woodward's Reagent K) and with the sulfhydryl specific blocker p chloromercuribenzene sulfonate inhibited T transport in both types of vesicles. Phenylglyoxal, but not ninhydrin, both reagents for arginine residues, and diethylpyrocarbonate, a reagent for histidine residues, specifically decreased T transport only in renal and small intestinal vesicles respectively. Similarly 7 chloro-4-nitrobenzo-2-oxa-1,3-diazole reacted, but not N-acetylimidazole, both of which are reagents for tyrosine residues. However, 7-chloro-4-nitrobenzo-2-oxa 1,3-diazole inhibition was aspecific. Acetylsalicylic acid, a reagent for lysine and serine residues, decreased T transport, but the lysine effect was aspecific. Acetylsalicylic acid serine blockage also eliminated T/H(+) exchange in small intestinal vesicles. Taken together, these results suggest that for T transport carboxylic and sulfhydryl groups and serine residues are essential in both renal and small intestinal brush border membrane vesicles. In addition, arginine and histidine residues are also essential respectively for renal and small intestinal transporters. Serine was essential for the T/H(+) antiport mechanism. PMID- 11779569 TI - Targeted delivery of indinavir to HIV-1 primary reservoirs with immunoliposomes. AB - The tissue distribution of indinavir, free or incorporated into sterically stabilized anti-HLA-DR immunoliposomes, has been evaluated after a single subcutaneous injection to C3H mice. Administration of free indinavir resulted in low drug levels in lymphoid organs. In contrast, sterically stabilized anti-HLA DR immunoliposomes were very efficient in delivering high concentrations of indinavir to lymphoid tissues for at least 15 days post-injection increasing by up to 126 times the drug accumulation in lymph nodes. The efficacy of free and immunoliposomal indinavir has been evaluated in vitro. Results showed that immunoliposomal indinavir was as efficient as the free agent to inhibit HIV-1 replication in cultured cells. The toxicity and immunogenicity of repeated administrations of liposomal formulations have also been investigated in rodents. No significant differences in the levels of hepatic enzymes of mice treated with free or liposomal indinavir were observed when compared to baseline and control untreated mice. Furthermore, histopathological studies revealed no significant damage to liver and spleen when compared to the control group. Liposomes bearing Fab' fragments were 2.3-fold less immunogenic than liposomes bearing the entire IgG. Incorporation of antiviral agents into sterically stabilized immunoliposomes could represent a novel therapeutic strategy to target specifically HIV reservoirs and treat more efficiently this retroviral infection. PMID- 11779570 TI - The presence of PEG-lipids in liposomes does not reduce melittin binding but decreases melittin-induced leakage. AB - Poly(ethyleneglycol) (PEG), anchored at the surface of liposomes via the conjugation to a lipid, is commonly used for increasing the liposome stability in the blood stream. In order to gain a better understanding of the protective properties of interfacial polymers, we have studied the binding of melittin to PEG-lipid-containing membranes as well as the melittin-induced efflux of a fluorescent marker from liposomes containing PEG-lipids. We examined the effect of the polymer size by using PEG with molecular weights of 2000 and 5000. In addition, we studied the role of the anchoring lipid by comparing PEG conjugated to phosphatidylethanolamine (PE) which results in a negatively charged PEG-PE, with PEG conjugated to ceramide (Cer) which provides the neutral PEG-Cer. Our results show that interfacial PEG does not prevent melittin adsorption onto the interface. In fact, PEG-PE promotes melittin binding, most likely because of attractive electrostatic interactions with the negative interfacial charge density of the PEG-PE-containing liposomes. However, PEG-lipids limit the lytic potential of melittin. The phenomenon is proposed to be associated with the change in the polymorphic tendencies of the liposome bilayers. The present findings reveal that the protective effect associated with interfacial hydrophilic polymers is not universal. Molecules like melittin can sense surface charges borne by PEG-lipids, and the influence of PEG-lipids on liposomal properties such as the polymorphic propensities may be involved in the so-called protective effect. PMID- 11779571 TI - Membrane-active properties of alpha-MSH analogs: aggregation and fusion of liposomes triggered by surface-conjugated peptides. AB - Reaction of the melanotropin hormone analogs [Nle(4),D-Phe(7)]-alpha-MSH and [Nle(4),D-Phe(7)]-alpha-MSH(4-10), which were extended at their N-terminus by a thiol-functionalized spacer arm, with preformed liposomes containing thiol reactive (phospho)lipid derivatives resulted in the aggregation of the vesicles and in a partial leakage of their inner contents. This aggregation/leakage effect, which was only observed when the peptides were covalently conjugated to the surface of the liposomes, was correlated with the fusion of the vesicles as demonstrated by the observed decrease in resonance energy transfer between probes in a membrane lipid mixing assay. A limited fusion was confirmed by monitoring the mixing of the liposome inner contents (formation of 1-aminonaphthalene-3,6,8 trisulfonic acid/p-xylene bis(pyridinium bromide) complex). The membrane-active properties of the peptides could be correlated with changes in the fluorescence emission spectra of their tryptophan residue, which suggested that after their covalent binding to the outer surface of the liposomes they can partition within the core of the bilayers. A blue shift of 10 nm was observed for [Nle(4),D Phe(7)]-alpha-MSH which was correlated with an increase in fluorescence anisotropy and with changes in the accessibility of the coupled peptide as assessed by the quenching of fluorescence of its tryptophan residue by iodide (Stern-Volmer plots). These results should be related to the previously described capacity of alpha-MSH, and analogs, to interact with membranes and with the favored conformation of these peptides which, via a beta-turn, segregate their central hydrophobic residues into a domain that could insert into membranes and, as shown here, trigger their destabilization. PMID- 11779572 TI - Investigation of interactions of a resorcin[4]arene receptor with bilayer lipid membranes (BLMs) for the electrochemical biosensing of mixtures of dopamine and ephedrine. AB - The present article investigates the interactions of a resorcin[4]arene receptor with planar bilayer lipid membranes (BLMs) that can be used for the electrochemical detection of dopamine and ephedrine. BLMs were composed of egg phosphatidylcholine and 35% (w/w) dipalmitoyl phosphatidic acid in which the receptor was incorporated. These BLMs modified with the resorcin[4]arene receptor can be used as one-shot sensors for the direct electrochemical sensing of these energizing-stimulating substances. The interactions of these compounds with the lipid membranes were found to be electrochemically transduced in the form of a transient current signal with a duration of seconds, which reproducibly appeared within 8 and 20 s after exposure of the membranes to dopamine and ephedrine, respectively. The response time for BLMs without the receptor for dopamine was about 3 min, whereas no signals were obtained for ephedrine in the absence of the receptor. The mechanism of signal generation was investigated by differential scanning calorimetric studies. These studies revealed that the adsorption of the receptor is through the hydrophobic tails of the receptor, whereas hydrophilic groups of the receptor were directed towards the electrolyte solution enhancing the ion transport through the lipid membranes. The magnitude of the transient current signal was related to the concentration of the stimulating agent in bulk solution in the micromolar range. No interferences from ascorbic acid were noticed because of the use of the negatively charged lipids in membranes. The present technique can be used as one-shot sensor for the detection of these pharmaceutical substances and future research is targeted to the determination of these chemicals in human biofluids such as urine of athletes. PMID- 11779573 TI - Neuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells. AB - Selegiline and rasagiline are selective and irreversible monoamine oxidase-B inhibitors that exert neuroprotective effects in various preclinical models. The aim of the present study was to examine the effect of selegiline and its major metabolite, L-methamphetamine in comparison to rasagiline and its major metabolite, 1-R-aminoindan on oxygen-glucose deprivation induced cell death in nerve growth factor (NGF)-differentiated pheochromocytoma (PC12) cells. Our results show that selegiline reduces oxygen-glucose deprivation induced cell death by 30%. When the cultures were treated with rasagiline at similar concentrations, cell death induced by oxygen-glucose deprivation was reduced by 45-55%. L-methamphetamine, a major selegiline metabolite, but not 1-R-aminoindan, the major rasagiline metabolite, enhanced oxygen-glucose deprivation-induced cell death by 70%. Under normoxic conditions, both metabolites lack neurotoxicity. Concomitant exposure of the cultures under oxygen-glucose deprivation, to a combination of either selegiline and L-methamphetamine or rasagiline and 1-R aminoindan, indicated that L-methamphetamine, but not 1-R-aminoindan, blocked the neuroprotective effect of the parental drug. These results suggest there may be a neuroprotective advantage of rasagiline over selegiline. PMID- 11779574 TI - Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum. AB - Parkinson-like extrapyramidal motor side effects associated with the use of antipsychotic drugs, such as increased muscle rigidity, are thought to result from blockade of striatal dopamine D2 receptors. While anticholinergic medications (muscarinic receptor antagonists) ameliorate extrapyramidal side effects, the mechanisms underlying their effectiveness remain unclear. We investigated the site of action of atropine, a non-selective muscarinic receptor antagonist, in reducing increased muscle rigidity, assessed as increases in tonic electromyographic (EMG) activity, induced by the selective dopamine D2 receptor antagonist, raclopride. Atropine significantly reduced raclopride-induced EMG increases in rat hindlimb muscles, when injected into the ventral striatum, but not the dorsal striatum or the substantia nigra. Atropine's site of action was localised to a small area of muscarinic receptors within the ventral part of the striatum, using quantitative autoradiography. These findings provide new information about the regulation of motor control by muscarinic receptor antagonists and additional evidence about the functional heterogeneity of the striatum. PMID- 11779575 TI - Differences in protective profiles of diltiazem isomers in ischemic and reperfused guinea pig hearts. AB - The effects of L-cis and D-cis diltiazem on the extracellular potassium concentration ([K(+)]e), pH and cardiac function were compared in ischemic guinea pig hearts. Before inducing ischemia, L-cis diltiazem (10 and 30 microM) reduced the left ventricular developed pressure (LVDP) with a marginal inhibition of heart rate (HR), whereas lower doses of the D-cis isomer decreased both LVDP and HR. L-cis Diltiazem only slightly inhibited the increase in [K(+)]e and the decrease in pH but significantly inhibited ischemic contractures in contrast to the marked inhibition of these parameters produced by even low doses of the D-cis isomer. Notably, at equipotent doses for the ischemic parameters, L-cis diltiazem restored the left ventricular end-diastolic pressure (LVEDP) and HR after reperfusion to a greater extent than the D-cis isomer. These results suggest that the L-cis isomer may specifically improve postischemic function, in addition to the modest action on [K(+)]e and pH, in guinea pig hearts. PMID- 11779576 TI - Severe impairment of CGRP-induced hypotension in vivo and vasorelaxation in vitro in elderly rats. AB - The aim of this study was to investigate the effects of aging on hypotension in vivo and vasorelaxation in vitro induced by calcitonin gene-related peptide (CGRP), using young (3 months old) and elderly (20 and 28 months old) Sprague Dawley rats. Vasorelaxant responses were measured in isolated rings of rat thoracic aorta and rat caudal artery, which show endothelium-dependent and endothelium-independent responses to CGRP, respectively. The CGRP-induced vasorelaxations were significantly diminished in 28-month-old male rats in both aorta (39.3% of responses in young controls at 10 nM CGRP) and caudal artery (28.5% of responses in young controls at 10 nM CGRP). Acetylcholine caused vasorelaxations in aortic rings of young male rats, but vasocontractions in aortic rings of 28-month-old male rats. Hypotension induced by CGRP was significantly diminished in both 20-month-old male rats (47.7% of young controls) and 20-month-old female rats (34.4% of young controls). Moreover, ovariectomy, known to decrease CGRP-induced hypotension in young female rats, did not further decrease hypotension to CGRP in elderly female rats. In conclusion, vasorelaxant responses in vitro and hypotensive responses in vivo induced by the neuropeptide CGRP are severely impaired in elderly rats as compared to young rats. The data suggest that the vasodilatory responses to CGRP in both large arteries and the small resistance-sized arteries regulating arterial blood pressure are damaged or down-regulated by the aging process. PMID- 11779577 TI - Raloxifene enhances nitric oxide release in rat aorta via increasing endothelial nitric oxide mRNA expression. AB - We report the modulatory effects of chronic oral LY139481 (raloxifene) on basal release of nitric oxide (NO) and mRNA levels of endothelial NO synthase (eNOS) in rat thoracic aorta. Constrictor dose-response curves to phenylephrine were generated before and after pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Aortic segments were obtained from four groups of rats gavaged orally for 21 days: (i) ovariectomized, (ii) sham, (iii) ovariectomized estradiol-treated, and (iv) ovariectomized raloxifene treated. Intact aortic rings from sham rats and ovariectomized rats receiving raloxifene and estrogen showed a greater potentiation of the phenylephrine responses after L-NAME. Semi-quantitative reverse transcription-polymerase chain reaction indicated a gender-based difference in eNOS mRNA expression in thoracic aorta. Moreover, we demonstrated that eNOS mRNA expression in the upper thoracic aorta was significantly higher in treatment groups. These results show that chronically administered raloxifene is exerting a potentially important vasculo protective effect by stimulating eNOS expression. PMID- 11779578 TI - Protein kinase C and the sub-sensitivity and sub-reactivity of the diabetic rat prostate gland to noradrenaline. AB - Concentration-response curves to noradrenaline (1 nM-100 microM) were obtained in prostates from 6-week streptozotocin diabetic, insulin-treated diabetic or control rats. Compared to the curve obtained in controls, those obtained in prostates from diabetic and insulin-treated diabetic rats were shifted rightward. The alpha1-adrenoceptor antagonist, prazosin (100 nM), caused a rightward shift of the curves in prostates from all groups. In contrast, the uptake 1 inhibitor, nisoxetine (300 nM), only produced a leftward shift of the curves in prostates from control and insulin-treated diabetic rats. However, frequency-response curves obtained in prostates from both control and diabetic rats were shifted leftward by nisoxetine (300 nM). The concentration-response curve to the alpha1 adrenoceptor agonist, methoxamine (10 nM-100 microM), obtained in prostates from diabetic rats was shifted rightward compared with controls. Calphostin C (500 nM), a protein kinase C inhibitor, caused a leftward shift of the curve in prostates from diabetic, but not control, rats. The protein kinase C inhibitor, bisindolylmaleimide I (500 nM), beta-adrenoceptor antagonist, propranolol (500 nM) and muscarinic cholinoceptor antagonist, atropine (300 nM), had no effect on the noradrenaline concentration-response curves of prostates from control or diabetic rats. Our results suggest that diabetes reduces the sensitivity and reactivity of the prostate to noradrenaline-induced stimulation, and this reduction may be due to changes in protein kinase C activity. PMID- 11779579 TI - Renal effects of glucagon-like peptide in rats. AB - The present study examined the effects of recombinant glucagon-like peptide-1-(7 36)amide (rGLP-1) on renal hemodynamics and excretory function in innervated and denervated kidneys of anesthetized rats. Intravenous infusion of rGLP-1 at a dose of 1 microg x kg(-1) x min(-1) increased urine flow and Na(+) excretion 13-fold in the innervated kidney. The natriuretic and diuretic response to rGLP-1 was attenuated in the denervated kidney in which urine flow and Na(+) excretion only increased 3-fold. Fractional excretion of Li(+), an index of proximal tubular reabsorption, increased 219% in the innervated kidney but only 54% in the denervated kidney during infusion of rGLP-1. The diuretic and natriuretic response to rGLP-1 was associated with an increase in glomerular filtration rate (39%) in the innervated kidney, but it had no effect on glomerular filtration rate in the denervated kidney. These results indicate that the natriuretic and diuretic effects of rGLP-1 are due to inhibition of Na(+) reabsorption in the proximal tubule. It also increases glomerular filtration rate in kidneys with an intact renal innervation. PMID- 11779580 TI - KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats. AB - KDR-5169, 4-amino-5-chloro-N-[1-(3-fluoro-4-methoxybenzyl)piperidin-4-yl]-2-(2 hydroxyethoxy)benzamide hydrochloride dihydrate, is a new prokinetic with a dual action, i.e., stimulation of the 5-HT4 receptor and antagonism of the dopamine D2 receptor. In this study, we determined in vitro activities of KDR-5169 towards both receptors and demonstrated the effect of the compound on gastrointestinal motor activity in conscious dogs and rats. In dogs, intravenous KDR-5169 stimulated upper gastrointestinal motility in the fasting state and also eliminated the depressive effect of 3,4-dihydroxyphenylalanine (L-DOPA) on this motility in the postprandial state. The effect of KDR-5169 on gastric emptying was further characterized by the use of three rat gastroparesis models (dopamine D2 receptor agonist (quinpirol)-, abdominal surgery-, or combined-situation induced). Domperidone (a dopamine D2 receptor antagonist) was effective in the quinpirol-delay and combination-delay models, and cisapride and mosapride (5-HT4 receptor agonists) were effective in the surgery-delay model. Only KDR-5169 eliminated the delay of gastric emptying in all three models. In addition, KDR 5169 accelerated emptying to above the normal level in the combination-delay model. These results suggest that KDR-5169 would be effective in various types of gastric ileus caused by different mechanisms. PMID- 11779581 TI - A pyrroloquinazoline derivative with anti-inflammatory and analgesic activity by dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase. AB - In a previous study, we reported a new pyrroloquinazoline derivative, 3-(4' acetoxy-3',5'-dimethoxy)benzylidene-1,2-dihydropyrrolo[2,1-b]quinazoline-9-one (PQ), which inhibited human purified 5-lipoxygenase activity and prostaglandin E2 release in lipopolysaccharide-stimulated RAW 264.7 cells. In the present work, we show that PQ inhibits cyclo-oxygenase-2 activity in intact cell assays (human monocytes) and purified enzyme preparations (ovine isoenzymes) without affecting cyclo-oxygenase-1 activity. This behaviour was confirmed in vivo by using the zymosan-injected mouse air pouch model, where PQ caused a marked reduction in cell migration and leukotriene B4 levels at 4 h, as well as inhibition of prostaglandin E2 levels without affecting cyclo-oxygenase-2 expression at 24 h after zymosan stimulation. In addition, oral administration of this compound significantly reduced carrageenan-induced mouse paw oedema and phenyl-p benzoquinone-induced writhings in mice. These results indicate that oral PQ exerts analgesic and anti-inflammatory effects, which are related to dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase activities. PMID- 11779582 TI - Participation of prostaglandin E2 and platelet-activating factor in thapsigargin induced production of interleukin-6. AB - Incubation of rat peritoneal macrophages in the presence of thapsigargin increased production of prostaglandin E2, intracellular platelet-activating factor (PAF) and interleukin-6. However, no PAF was detected in the conditioned medium. In the presence of SK&F 98625 (diethyl 7-(3,4,5-triphenyl-2-oxo-2,3 dihydroimidazol-1-yl)heptane phosphonate), a CoA-independent transacylase inhibitor, the thapsigargin-induced increases in the interleukin-6 mRNA level and interleukin-6 production were suppressed in a concentration-dependent manner. This inhibitor also suppressed the production of prostaglandin E2 and intracellular PAF. The PAF receptor antagonists such as E6123 ((S)-(+)-6-(2 chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine) and L 652,731 (2,5-bis(3,4,5-trimethylphenyl)tetrahydrofuran) partially inhibited the thapsigargin-induced increase in the levels of interleukin-6 mRNA and interleukin 6 protein. The SK&F 98625-induced suppression of interleukin-6 mRNA accumulation and interleukin-6 production was partially restored by addition of exogenous prostaglandin E2. However, exogenous PAF failed to reverse the suppression suggesting that the intracellular PAF does not act in an autocrine mechanism. These findings suggested that the concurrently produced prostaglandin E2 and intracellular PAF participate in the thapsigargin-induced increase in the interleukin-6 mRNA level and interleukin-6 production by rat peritoneal macrophages. PMID- 11779584 TI - Triphasic oral contraceptives: review and comparison of various regimens. AB - OBJECTIVE: To review and compare the risk-benefit profile of triphasic oral contraceptives with that of low-dose monophasic oral contraceptives. DESIGN: Literature on currently marketed triphasics and monophasics. PATIENT(S): Healthy women of reproductive age. MAIN OUTCOME MEASURE(S): Comparison of the rationale for development, composition, mechanism, efficacy, menstrual cycle control, side effects, health benefits, and risk-benefit profile. RESULT(S): All triphasics contain ethinyl estradiol (0.025-0.040 mg/d) and one of several progestins in doses (0.05-1.0 mg/d) related to their relative potencies, which are substantially lower overall (total dose) than those in monophasics. The triphasics are highly efficacious. In general, menstrual cycle control and side effects are similar in both types, but triphasics containing the newer progestins (desogestrel, gestodene, and norgestimate) have better cycle control and a reduced incidence of androgenic side effects compared with those with norethindrone or levonorgestrel. Both triphasics and monophasics have minimal effects on carbohydrate and lipid metabolism and hemostasis parameters, and therefore comparable low risks of coronary heart disease. The health benefits of triphasics and monophasics are similar and include decreased incidence of unwanted and ectopic pregnancies, ovarian cysts, endometrial and ovarian cancers, benign breast disease, and acute pelvic inflammatory disease; less menstrual blood loss and iron deficiency anemia; and lower frequency of irregular bleeding and menorrhagia. CONCLUSION(S): The risk-benefit profiles of both triphasics and monophasics are favorable and similar. PMID- 11779583 TI - Chronic acarbose-feeding increases GLUT1 protein without changing intestinal glucose absorption function. AB - As alpha-glucosidase inhibitor, the antidiabetic drug acarbose reduces postprandial glucose levels by retarding the intestinal digestion of polysaccharides. However, it is unknown if acarbose also affects the expression of intestinal glucose transporters, especially the Na(+)-glucose cotransporter (SGLT1) and the glucose transporters GLUT1 and GLUT2. To unravel this question, Wistar rats received standard powdered chow either without (control) or with acarbose (40 mg acarbose/100 g chow) for 40 days. While food intake was slightly enhanced by acarbose, the drug had no influence on weight gain or plasma glucose and insulin levels. The acarbose-treatment did not alter the SGLT1 and GLUT2 gene expression in both upper and middle small intestine, whereas GLUT1 protein was increased by 75% in middle small intestine. Despite the territorial change in GLUT1 protein, the intestinal glucose absorption in an acarbose-free perfusion study was unaltered. In conclusion, the chronic use of acarbose did not alter the acarbose-free glucose absorption profile. PMID- 11779585 TI - Phytoestrogens: are they really estrogen mimics? PMID- 11779586 TI - Assisted reproductive technology in the United States: 1998 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. AB - OBJECTIVE: To summarize the procedures and outcomes of ART initiated in the United States in 1998. DESIGN: Data were collected electronically by using the SART Clinical Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANT(S): Three hundred and sixty programs submitted data on procedures performed in 1998. Data were collated after November 1999 so that the outcome of all pregnancies established would be known. MAIN OUTCOME MEASURE(S): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. RESULTS: Programs reported initiating 81,899 cycles of ART treatment. Of these, 58,937 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 29.1%; 1,293 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 27.4%; 1,054 were cycles of zygote intrafallopian transfer with a delivery rate per retrieval of 29.6%. The following additional ART procedures were also initiated: 5,273 fresh donor oocyte cycles, with a delivery rate per transfer of 41.2%; 11,228 frozen embryo transfer procedures, with a delivery rate per transfer of 19.3%; 1,913 frozen embryo transfers using donated oocytes or embryos, with a delivery rate per transfer of 23.5%, and 809 cycles using a host uterus, with a delivery rate per transfer of 31.6%. In addition, 969 cycles were reported as combinations or more than one treatment type, 25 cycles as research, and 398 as embryo banking. As a result of all procedures, 20,241 deliveries were reported, resulting in 29,128 neonates. CONCLUSIONS: In 1998, there were more programs reporting ART treatment and a significant (12.1%) increase in reported cycles compared with 1997. In comparable cycle types, the actual increase in overall success rate (deliveries per retrieval) was 1.4%, which represents an increase of 4.7% compared with the success rate in 1997. PMID- 11779587 TI - Ureteral endometriosis: a complication of rectovaginal endometriotic (adenomyotic) nodules. AB - OBJECTIVE: To present data from 18 cases of ureteral endometriosis. DESIGN: Prospective clinical study. SETTING: Department of gynecology at a university hospital. PATIENT(S): Four hundred and five patients with severe dysmenorrhea or deep dyspareunia due to a rectovaginal endometriotic (adenomyotic) nodule. INTERVENTION(S): Patients were prospectively evaluated using intravenous pyelography. All patients underwent laparoscopic surgery to remove rectovaginal adenomyosis and ureterolysis. MAIN OUTCOME MEASURE(S): Presurgical and postsurgical evaluation and histologic analysis. RESULT(S): Preoperative intravenous pyelography revealed ureteral stenosis with ureterohydronephrosis in 18 patients (4.4%). A significantly higher prevalence (11.2%) was observed in nodules > or = 3 cm in diameter. Five women (20%) had complete ureteral stenosis. Kidney scintigraphy revealed damaged kidney parenchymal function, which ranged from 18% to 42%. Laparoscopic ureterolysis was done in 16 women; 2 women underwent ureteral resection and uretero-ureterostomy. A significant postoperative decrease in ureterohydronephrosis was noted in all patients; however, renal function improved only slightly. CONCLUSION(S): Ureteral endometriosis was found in 4.4% of patients with rectovaginal endometriotic (adenomyotic) nodules. Ureterolysis and removal of associated adenomyotic lesions was sufficient therapy in most patients; two required resection of the ureteral stenotic segment. Intravenous pyelography should be performed in all women with rectovaginal nodules > or = 3 cm to prevent nonreversible loss of renal function. PMID- 11779588 TI - DNA microarray analysis of gene expression markers of endometriosis. AB - OBJECTIVE: To use DNA microarray technology to examine differential gene expression in uterine endometrium versus endometriosis implants. DESIGN: Pilot study. SETTING: Volunteers in an academic research environment. PATIENT(S): Premenopausal women scheduled for surgery for suspected endometriosis. INTERVENTION(S): Surgical excision of endometriosis tissue and uterine endometrial biopsy. MAIN OUTCOME MEASURE(S): Gene expression. RESULT(S): The expression of eight genes from a total of 4,133 genes on the DNA microarray was increased in endometriosis implants compared with uterine endometrium. The eight genes were beta-actin, alpha-2 actin, vimentin, 40S ribosomal protein S23, Ig lambda light chain, Ig germline H chain G-E-A region gamma-2 constant region gene, major histocompatibility complex class 1,C, and complement component 1 S subcomponent. CONCLUSION(S): The data demonstrate that the DNA microarray is an effective tool for the identification of differentially expressed genes between uterine and ectopic endometrium; further study of the genes identified herein will expand our understanding of the nature of endometriosis and assist in the eventual development of new treatments for endometriosis. PMID- 11779589 TI - The proline form of p53 codon 72 polymorphism is associated with endometriosis. AB - OBJECTIVE: To evaluate the association between endometriosis and the p53 polymorphism. DESIGN: Prospective study. SETTING: Department of gynecology and genetics in a medical center. PATIENT(S): Women with and without endometriosis. INTERVENTION(S): Women were categorized as having moderate or severe endometriosis (n = 118) or no endometriosis (n = 140). MAIN OUTCOME MEASURE(S): Polymerase chain reaction was used to detect p53 codon 72 polymorphisms (arginine homozygosity, heterozygosity, and proline homozygosity). Associations between endometriosis and p53 polymorphisms were evaluated. RESULT(S): The distributions of different p53 polymorphisms differed significantly between groups. The respective proportions of arginine homozygotes, heterozygotes, and proline homozygotes were 10.2%, 66.9%, and 22.9% in the group with endometriosis and 30.7%, 50%, and 19.3% in the group without endometriosis. CONCLUSION(S): Endometriosis is associated with p53 polymorphism. p53 arginine homozygotes have lower risk for endometriosis. Heterozygotes and proline homozygotes have higher risk for endometriosis. PMID- 11779590 TI - Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility. AB - OBJECTIVE: Determine whether peritoneal macrophages from women with endometriosis associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls. DESIGN: Unblinded clinical study. PATIENT(S): Nine infertile women with endometriosis and nine normal fertile women undergoing laparoscopy. INTERVENTION(S): Peritoneal fluid and macrophages were collected. Cells were also cultured with the NOS2 inducers interferon-alpha (IFN alpha) or IFN-gamma plus lipopolysaccharide (LPS). MAIN OUTCOME MEASURE(S): Peritoneal fluid NO levels, peritoneal macrophage NOS activity, and peritoneal macrophage NOS2 protein expression. RESULT(S): NOS enzyme activity was higher in peritoneal macrophages from endometriosis patients. Immunoblots demonstrated NOS2 protein only in peritoneal macrophages from women with endometriosis. Peritoneal fluid NO concentration was similar in the two groups, but total peritoneal fluid NO content was higher in endometriosis patients. After 3 days' culture, peritoneal macrophages from women with endometriosis produced more NO in response to IFN-alpha or IFN-gamma plus LPS than controls. CONCLUSION(S): Peritoneal macrophages from women with endometriosis-associated infertility express higher levels of NOS2, have higher NOS enzyme activity, and produce more NO in response to immune stimulation in vitro. As high levels of NO adversely affect sperm, embryos, implantation, and oviductal function, reducing peritoneal fluid NO production or blocking NO effects may improve fertility in women with endometriosis. PMID- 11779591 TI - Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. AB - OBJECTIVE: To evaluate the efficacy and safety of cyproterone acetate versus an oral contraceptive in the treatment of endometriosis-associated recurrent pelvic pain. DESIGN: Randomized controlled trial. SETTING: Academic center. PATIENT(S): Ninety women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis. INTERVENTION(S): Six months of continuous treatment with oral cyproterone acetate, 12.5 mg/d, or an oral contraceptive containing ethinyl estradiol, 0.02 mg, and desogestrel, 0.15 mg. MAIN OUTCOME MEASURE(S): Degree of satisfaction with therapy. RESULT(S): Six patients in the cyproterone acetate arm and nine in the oral contraceptive arm withdrew because of side effects (n = 9), treatment inefficacy (n = 4), or loss to follow-up (n = 2). At 6 months, dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain scores were substantially reduced, and significant improvements were observed in health-related quality-of-life, psychiatric profile, and sexual satisfaction; no major between-group differences were seen. Subjective and metabolic side effects were limited. According to an intention-to-treat analysis, 33 of 45 (73%) of patients in the cyproterone acetate group and 30 of 45 (67%) in the oral contraceptive group were satisfied with the treatment received. CONCLUSIONS: Both cyproterone acetate and a continuous monophasic oral contraceptive were effective, safe, and inexpensive therapy for recurrent pain after conservative surgery for endometriosis. PMID- 11779592 TI - Effect of interleukin-8 (IL-8), anti-IL-8, and IL-12 on endometrial cell survival in combined endometrial gland and stromal cell cultures derived from women with and without endometriosis. AB - OBJECTIVE: To study the affects of interleukin-8 (IL-8), anti-IL-8, and IL-12 on in vitro proliferation of endometrial cells. DESIGN: An in vitro study. SETTING: Department of Obstetrics and Gynecology, University of Aberdeen, UK. PATIENT(S): Women attending a fertility clinic. INTERVENTION(S): In vitro cell cultures using culture media supplemented with IL-8 (100 ng/mL, 200 ng/mL, and 500 ng/mL), IL-12 (1 ng/mL, 5 ng/mL, and 25 ng/mL), and anti-IL-8 (0.1 microg/mL, 1 microg/mL, 10 microg/mL). MAIN OUTCOME MEASURE(S): In vitro survival of dispersed endometrial cells (combined epithelial and glandular) at 5 and 9 days of culture. RESULT(S): There was a dose-dependent stimulatory effect of IL-8 on survival of cells. From women with and without endometriosis, IL-12 at 1 ng/mL significantly inhibited the survival of endometrial cells from women without endometriosis as compared with cells from women with endometriosis. At 1 microg/mL, anti-IL-8 significantly inhibited the survival of endometrial cells from women with endometriosis compared with cells from women without endometriosis on day 5 of culture. CONCLUSION(S): Our findings confirm the stimulatory effects of IL-8 and its possible role in the pathogenesis of endometriosis. The effects of IL-12 and anti IL-8 on endometrial cell survival varied according to the disease state and the concentration of the cytokines. Future in vitro studies on the role of anti-IL-8 and IL-12 should aim to use a greater range of concentrations and a higher density of endometrial cells in cultures supplemented with monocytes. PMID- 11779593 TI - Reduced copy number of DAZ genes in subfertile and infertile men. AB - OBJECTIVE(S): To determine the copy number and identity of the DAZ genes on the Y chromosomes of infertile patients. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): One hundred and thirty-nine patients with male factor infertility. INTERVENTION(S): The separate genes were detected by polymerase chain reaction (PCR) digestion assays of sequence family variants in leukocyte DNA and by fluorescence in situ hybridization of interphase nuclei and chromatin fibers. MAIN OUTCOME MEASURE(S): Number of DAZ genes present. RESULT(S): One hundred twenty-nine patients had four genes, 6 patients had two genes, and 4 patients had none. Three patients had a deletion of the two proximal DAZ genes, and three were missing both distal genes. Semen analysis showed a less severe phenotype in patients with only two DAZ genes compared with patients missing all four genes. CONCLUSION(S): In six patients, two different partial deletions were found that were not detected by PCR with conventional markers. One patient with an AZFb deletion appeared to also have a partial AZFc deletion that was not detected by routine PCR. Phenotypic differences between patients with different deletions suggest a dose effect of the DAZ genes. PMID- 11779594 TI - Serum sperm antibodies are not elevated after mumps orchitis. AB - OBJECTIVE: To assess the level of serum sperm antibodies after mumps orchitis. DESIGN: Controlled descriptive study. SETTING: Academic research environment. PATIENT(S): Seventy-four mumps orchitis patients. INTERVENTION(S): Sampling of serum at different intervals after the onset of orchitis symptoms: 1 to 7 days, 31 to 60 days, and 61 to 431 days. MAIN OUTCOME MEASURE(S): Level of serum sperm antibodies, using Kibrick's gelatin agglutination test, Friberg's tray agglutination test, Isojima's sperm immobilization test, and ELISA. RESULT(S): Clinically relevant sperm antibody values were detected by the Friberg method among patients tested from 1 to 7 days (10.5%) and 61 to 431 days (10.5%) after the onset of disease. The Isojima test revealed a statistically insignificant higher incidence among patients at 61 to 431 days (31.6%) as compared with those sampled at 1 to 7 days (10.5%). None of the orchitis sera tested positive by the Kibrick and ELISA techniques. The established incidences did not differ significantly from the results for negative controls (blood donors) and were lower than the values acquired from positive controls (males with unexplained infertility). CONCLUSION(S): Mumps orchitis does not cause enhanced humoral immunity to spermatozoa. PMID- 11779595 TI - Prediction of the individual follicle-stimulating hormone threshold for gonadotropin induction of ovulation in normogonadotropic anovulatory infertility: an approach to increase safety and efficiency. AB - OBJECTIVE: To predict the FSH response (threshold) dose in normogonadotropic, anovulatory infertile women undergoing gonadotropin induction of ovulation. DESIGN: Prospective longitudinal clinical study. SETTING: Specialist academic fertility unit. PATIENT(S): Normogonadotropic, oligoamenorrheic, infertile women who were resistant to clomiphene citrate or in whom clomiphene citrate therapy had failed. INTERVENTION(S): Daily exogenous FSH administration in a low-dose, step-up regimen. MAIN OUTCOME MEASURE(S): The FSH dose on the day of ovarian response (follicle growth > 10 mm in diameter). RESULT(S): Multivariate analysis was used to devise the following equation to predict the individual FSH response dose (75 to >187 IU/d) before initiation of therapy: [4 body mass index (in kg/m(2))] + [32 clomiphene citrate resistance (yes = 1 or no = 0)] + [7 initial free insulin-like growth factor-I (in ng/mL)] + [6 initial serum FSH level (in IU/L)] - 51. The SE of the predicted dose is 35 IU. CONCLUSION(S): The individual FSH response dose for gonadotropin induction of ovulation in anovulatory infertile women can be predicted on the basis of initial screening characteristics. The prediction model developed in this study may increase the safety and efficiency of low-dose gonadotropin protocols (step-up and step-down) by correctly determining the appropriate starting dose for a given patient. PMID- 11779596 TI - A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. AB - OBJECTIVE: To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate (CC). DESIGN: Prospective longitudinal single-center study. SETTING: Specialist academic fertility unit. PATIENT(S): Two hundred fifty-nine couples with a history of infertility, oligoamenorrhea, and normal follicle-stimulating hormone (FSH) concentrations who have not been previously treated with any ovulation-induction medication. INTERVENTION(S): 50, 100, or 150 mg of oral CC per day, for 5 subsequent days per cycle. MAIN OUTCOME MEASURE(S): Conception leading to live birth after CC administration. RESULT(S): After receiving CC, 98 (38%) women conceived, leading to live birth. The cumulative live birth rate within 12 months was 42% for the total study population and 56% for the ovulatory women who had received CC. Factors predicting the chances for live birth included free androgen index (testosterone/sex hormone-binding globulin ratio), body mass index, cycle history (oligomenorrhea versus amenorrhea), and the woman's age. CONCLUSION(S): It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram. Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility. Alternative first line of treatment options could be considered for some women who have limited chances for success. PMID- 11779597 TI - A minimally monitored assisted reproduction stimulation protocol reduces cost without compromising success. AB - OBJECTIVE: To determine if a fixed-dose stimulation protocol with monitoring limited to a single ultrasound can provide acceptable outcomes in assisted reproduction technologies (ART) procedures in appropriately selected patients. DESIGN: Prospective study of all minimally monitored ART cycles from 1996 through 1998. SETTING: University ART program. PATIENTS: Eligibility included Institutional Review Board consent, age 18-37, basal FSH < or = 10, normal semen parameters, and regular menses. IVF (n = 81) and GIFT (n = 14). INTERVENTIONS: A single ultrasound was performed after 8 or 9 days of stimulation in a fixed schedule long luteal phase leuprolide protocol. No hormone levels were obtained. Human chorionic gonadotropin was administered when at least 2 follicles were projected to reach 18 mm. MAIN OUTCOME MEASURES: Pregnancy, delivery, and implantation rates. RESULTS: The clinical pregnancy rates were 51% for IVF and 36% for GIFT. Delivery rates were 42% for IVF and 29% for GIFT. The implantation rates for IVF were 23% and 17% for GIFT. No patient was admitted for ovarian hyperstimulation. CONCLUSIONS: We were able to achieve satisfactory pregnancy and delivery rates in properly selected patients with a minimal monitoring protocol, limited to a single ultrasound near the end of a fixed-stimulation regimen. The reduced time commitment and cost led to a very high patient acceptance of this approach. PMID- 11779598 TI - Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. AB - OBJECTIVE: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Infertility clinic of a tertiary referral center. PATIENT(S): Fifty-six women with clomiphene citrate-resistant PCOS. INTERVENTION(S): Two cycles of oral metformin therapy (850 mg, twice daily) in group I and placebo therapy (twice daily) in group II. Clomiphene citrate (100 mg/day) on cycle days 3-7 of the second cycle in both groups. MAIN OUTCOME MEASURE(S): Insulin, T, DHEAS, FSH, LH, body mass index (BMI), waist-to-hip ratio, endometrial thickness, cervical score, ovulation, and pregnancy rates in clomiphene-induced cycles after metformin therapy. RESULT(S): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI. No difference in waist-to-hip ratio, DHEAS level, and fasting insulin level was observed. Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group. There was higher cumulative pregnancy rate in the metformin group; however, there was no significant difference in the pregnancy rate between the two groups. CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS. PMID- 11779599 TI - Analysis of the cost effectiveness of recombinant versus urinary follicle stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection programs in the United States. AB - OBJECTIVE: To compare the cost effectiveness of recombinant human FSH (Gonal-F; Serono, Inc., Randolph, MA) and urinary FSH (Fertinex; Serono, Inc.) for ovarian stimulation during IVF with or without intracytoplasmic sperm injection for the treatment of infertility. DESIGN: Clinical decision analysis techniques (the Markov model) were used to model the direct medical costs per patient during assisted reproductive technology. MAIN OUTCOME MEASURE(S): Clinical and economic outcomes of two different ovarian stimulation protocols (recombinant human FSH or urinary FSH) during three treatment cycles were considered. RESULT(S): More ongoing pregnancies were achieved, with fewer stimulation cycles, after recombinant human FSH (Gonal-F) than after urinary FSH (Fertinex) (40,665 versus 37,890). In addition, recombinant human FSH was also found to be more cost effective per ongoing pregnancy. From a societal perspective, the mean cost per pregnancy was $40,688 for recombinant human FSH versus $47,096 for urinary FSH. From the insurers' perspective, the mean cost/pregnancy for recombinant human FSH was $28,481 versus $32,967 for urinary FSH. CONCLUSION(S): Recombinant human FSH (Gonal-F) is not only more efficient clinically than urinary FSH (Fertinex), but also more cost effective. This analysis illustrates the point that the economic effectiveness of a drug depends less on its acquisition costs and rather more on the clinical outcomes associated with its use. PMID- 11779600 TI - Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome. AB - OBJECTIVE: To evaluate the efficacy of blastocyst culture and transfer in human in vitro fertilization (IVF) as compared to day 3 embryo transfer. DESIGN: Prospective randomized trial. SETTING: Private assisted reproduction unit. PATIENT(S): A total of 162 IVF patients were included in the day 3 embryo transfer (n = 82) and blastocyst transfer (n = 80) groups. INTERVENTION(S): Embryo transfer on day 3 after culture in the standard culture media and blastocyst transfer on day 5 or 6 after culture in the sequential culture media. MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates, multiple gestation rate. RESULT(S): The implantation rate for embryos transferred at the blastocyst stage was significantly higher than that for embryos transferred on day 3 (26% vs. 13%). The viable pregnancy rate was similar in both groups (29% vs. 26%). Significantly fewer embryos were required for transfer at the blastocyst stage compared with day 3 embryo transfer (2.0 +/- 0.1 vs. 3.5 +/- 0.63). The high order multiple gestation rate was significantly less with the blastocyst transfer than with the day 3 embryo transfer (4% vs. 19%). CONCLUSION(S): With the use of blastocyst culture, a few embryos can be transferred without decreasing the overall pregnancy rate. This may reduce multiple gestations and improve human IVF outcome. PMID- 11779601 TI - Reproductive health in individuals with homozygous beta-thalassemia: knowledge, attitudes, and behavior. AB - OBJECTIVE: To review the reproductive health knowledge, attitudes, and behaviors of persons with homozygous beta-thalassemia. DESIGN: Case-control study. SETTING: Patients treated at a tertiary hospital and community-based healthy controls. PARTICIPANT(S): One hundred and thirty persons, 16 years of age or older, who had homozygous beta-thalassemia and were attending hospital for regular blood transfusion, and 99 demographically matched persons without thalassemia. ASSESSMENT TOOL: Reproductive health questionnaire. RESULT(S): 104 (80%) persons with homozygous beta-thalassemia completed the questionnaire and were compared with 99 controls. Persons with homozygous beta-thalassemia were as likely as healthy peers to be in a relationship, employed full-time, sexually active, and using contraception and to have had children. Hypogonadotrophic hypogonadism was present in 55 (52.8%) patients, 46 (83.6%) of whom were compliant with hormone replacement therapy. Understanding of genetics and reproductive potential was suboptimal among persons with homozygous beta-thalassemia, and this group had a higher rate of unplanned pregnancy. CONCLUSION(S): This study suggests that with optimal therapy, most young adults with homozygous beta-thalassemia can achieve reproductive, sexual, and social experiences similar to those of their healthy peers. PMID- 11779602 TI - Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. AB - OBJECTIVE: To determine whether postmenopausal status is associated with elevated plasma inflammation markers compared to premenopausal status, and how this explains differences in fat distribution and insulin-stimulated glucose disposal. DESIGN: Cross-sectional. SETTING: Clinical research center. PATIENT(S): Forty five premenopausal women and 44 postmenopausal women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA. Intraabdominal, subcutaneous abdominal, and total fat were measured by computed tomographic scan and dual-photon x-ray absorptiometry. Insulin-stimulated glucose disposal was measured by euglycemic clamp. RESULT(S): The TNF-alpha was higher in postmenopausal compared to premenopausal women (4.81 +/- 1.99 vs. 3.54 +/- 0.85 pg/mL). Interleukin-6 and CRP did not differ by menopausal status. In both premenopausal and postmenopausal women, CRP was related positively to total fat. The CRP was related to intraabdominal fat only in postmenopausal women and was negatively related to insulin-stimulated glucose disposal in both premenopausal and postmenopausal women. CONCLUSION(S): Postmenopausal status is characterized by higher TNF-alpha. The CRP may be associated with increased cardiovascular risk in postmenopausal women by its association with higher intraabdominal fat. Higher CRP is associated with lower insulin-stimulated glucose disposal in both premenopausal and postmenopausal women. PMID- 11779603 TI - Adolescent Caucasian mothers have reduced adult hip bone density. AB - OBJECTIVE: To determine the long-term effect of full term teen pregnancy on peak hip bone mineral density. DESIGN: Longitudinal observational study. SETTING: Academic clinical research center. PATIENT(S): Sixteen non-Hispanic white females: 4 cases and 12 matched controls who are part of The Penn State Young Women's Health Study and have been studied from ages 12 to 21. MAIN OUTCOME MEASURES: Four of the subjects had uncomplicated full-term pregnancies between ages 16.5 and 19.5 years. INTERVENTION(S): The cases and controls were matched for body mass index at age 12 years, total body bone mineral content at age 12 years, age of menarche, and sports-exercise score during ages 12-18 years. They were then compared with respect to bone measures, cardiovascular disease risk factors, and endocrine profiles at ages 19-21 years. RESULT(S): The four teen mothers had significantly lower adult hip bone mineral density than did the controls (0.89 g/cm(2) vs. 0.99 g/cm(2); P=.03). The reproductive hormone patterns of the cases were not statistically significantly different from those of the controls, yet the cases showed a postmenopausal blood lipid pattern. CONCLUSION(S): The persistent reduction in hip bone mineral density of the cases is consistent with significantly increased risk of future hip fracture. PMID- 11779604 TI - Relationship between serum mullerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women. AB - OBJECTIVE: To examine the relationship of serum mullerian-inhibiting substance (MIS), E(2), free-T, LH, and FSH in untreated women with polycystic ovary syndrome (PCOS) and in women with normal menstrual cycles. DESIGN: A prospective study. SETTING: University Departments of Obstetrics and Gynecology and Surgery. PATIENT(S): Twenty-seven women with PCOS and 20 women with normal menstrual cycles. INTERVENTION(S): Serum was collected from women with PCOS and from normal women during the early follicular phase of the menstrual cycle, stored frozen until assayed. MAIN OUTCOME MEASURE(S): Serum levels of MIS, E(2), free-T, TSH, LH, and FSH were measured. RESULT(S): Serum mullerian-inhibiting substance levels in PCOS patients were significantly higher compared with normal women (+/- SE; 5.3 +/- 0.7 and 1.4 +/- 0.2 ng/mL, respectively). An inverse correlation (r = 0.5965) was found between serum levels of MIS and E(2) in PCOS women, but not in normal women. Women with PCOS had higher serum LH levels than those of normal women (15.2 +/- 1.2 and 5.0 +/- 0.7 mIU/mL). CONCLUSION: In this study, women with PCOS have significantly higher serum MIS levels than normal women. The inverse relationship between mullerian-inhibiting substance and E(2) levels suggests that MIS may modulate ovarian E(2) synthesis and have a role in the disordered folliculogenesis characteristic of PCOS. PMID- 11779605 TI - Inducible and endothelial nitric oxide synthase: genetic background affects ovulation in mice. AB - OBJECTIVE: Inducible nitric oxide synthase (NOS) and endothelial NOS are involved in female reproductive physiology. We sought to investigate the influence of the inducible (Nos2) and endothelial (Nos3) NOS genes as a function of genetic background on ovulatory capacity and early embryonic development in a mouse model. DESIGN: Observational study of genetically altered mice and their response to a superovulation protocol. SETTING: Academic research institution. ANIMALS: Wild-type mice and mice deficient for Nos2 or Nos3 were bred to C57BL/6J and 129/Sv genetic backgrounds. INTERVENTION(S): Superovulation protocol, oocyte culture. MAIN OUTCOME MEASURE(S): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology. RESULT(S): The mean number of oocytes was significantly reduced in Nos3 deficient mice on a C57BL/6J background compared with controls. Oocytes deficient for Nos3 on a C57BL/6J background also showed reduced progression to two-cell stage embryos after 24 hours, two-cell stage embryos to blastocyst stage embryos, and survival to 48 hours. Those effects were distinctly absent in mice deficient for Nos3 on a 129/Sv background and in mice deficient for Nos2 on either genetic background. CONCLUSION(S): Our data show that disruption of Nos2 had no effect on ovulation in our mice. The negative effect of Nos3 deficiency on ovulatory capacity and early embryonic development is modulated by genetic background. This suggests a role for strain-specific modifier genes in these processes. PMID- 11779606 TI - Beneficial effect of microinjected trehalose on the cryosurvival of human oocytes. AB - OBJECTIVE: To determine the effectiveness of trehalose as an intracellular cryoprotectant for the cryopreservation of human oocytes. DESIGN: In vitro comparative study. SETTING: Clinical and academic research environment at a medical school teaching hospital. PATIENT(S): Women undergoing in vitro fertilization (IVF). INTERVENTION(S): Discarded human oocytes, obtained from IVF patients, were randomly distributed into three groups: control group (no trehalose), extracellular trehalose group (0.5 M extracellular trehalose), and intracellular trehalose group (0.15 M intra- and 0.5 M extracellular trehalose). Trehalose was introduced into oocytes by microinjection. The oocytes in each group were cooled to different temperatures (i.e., -15 degrees C, -30 degrees C, and -60 degrees C) at rate of 1 degrees C/minute and thawed at ambient air temperature. Survival was examined after overnight culture. MAIN OUTCOME MEASURE(S): Survival of human oocytes cryopreserved in the presence and absence of trehalose. RESULT(S): The majority of oocytes in the intracellular trehalose group survived cooling to -15 degrees C (63%), -30 degrees C (53%), and -60 degrees C (66%). In contrast, only a small number of oocytes in both the control (13%) and extracellular trehalose group (22%) survived cooling to -15 degrees C, while all oocytes degenerated when cooled to -30 degrees C and -60 degrees C. CONCLUSION(S): Small amounts of intracellular trehalose in the absence of any other cryoprotectant provide a significant protection against freeze-associated stresses. Our results suggest that sugars such as trehalose should be considered as intracellular cryoprotectants for cryopreservation of human oocytes. PMID- 11779607 TI - VAMP/synaptobrevin as an acrosomal marker for human sperm. AB - OBJECTIVE: To determine the possible use of the mammalian acrosomal marker vehicle-associated membrane protein (VAMP)/synaptobrevin to detect acrosome abnormalities in human sperm. DESIGN: Analysis of human sperm after fixation and staining with an anti-VAMP antibody. SETTING: An academic research institution. PATIENT(S): Semen samples from consenting patients who were participating in an infertility treatment program. INTERVENTION(S): Human sperm samples were fixed, permeabilized with detergent, and examined by immunocytochemistry. MAIN OUTCOME MEASURE: Immunostaining. RESULT(S): Observation of sperm from patients with no obvious sperm morphological defects revealed normal looking acrosomes, as assessed by VAMP immunostaining. However, severe acrosome malformations were detected in other cases. The observations registered varied from the absence of a fully formed organelle in samples of patients with globozoospermia to abnormal VAMP staining in samples from patients with acrosomal defects. CONCLUSION: VAMP/synaptobrevin may be a useful marker for the functional assessment of acrosomal status in human sperm. PMID- 11779608 TI - Chlamydial heat shock protein 60--specific T cells in inflamed salpingeal tissue. AB - OBJECTIVE: To evaluate the role of chlamydial heat shock protein 60 (CHSP60) specific T-lymphocytes in tubal factor infertility. DESIGN: Case series of patients with tubal factor infertility. SETTING: Infertility Clinic, Department of Obstetrics and Gynecology, Helsinki University Central Hospital and Laboratory of Cell-Mediated Immunity, National Public Health Institute, Oulu, Finland. PATIENT(S): Five patients with tubal factor infertility who underwent elective salpingectomy because of hydrosalpinges. INTERVENTION: Collection of salpingeal tissue specimens for in vitro culture of T-lymphocytes. MAIN OUTCOME MEASURE(S): Cloning of Chlamydia trachomatis and CHSP60-specific T-lymphocyte lines derived from inflamed salpingeal tissue. Cytokine production analysis of the established T-lymphocyte clones. RESULT(S): Seventy-seven (34%) of the 229 T-lymphocyte clones recognized C. trachomatis and C. pneumoniae elementary bodies as target antigens. One-third of these Chlamydia genus-specific T-lymphocyte clones further recognized CHSP60 as the target antigen. Most of the CHSP60-specific T-lymphocyte clones produced predominantly IL-10. CONCLUSION(S): CHSP60 may be an important T lymphocyte antigen involved in the immunopathogenesis of tubal damage associated with chronic C. trachomatis infection. PMID- 11779609 TI - Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. AB - OBJECTIVE: To determine whether there is an ovarian thecal cell component to hyperandrogenism exhibited in adult female rhesus monkeys exposed to androgen excess during prenatal life. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. ANIMAL(S): Eleven adult female rhesus monkeys. INTERVENTION(S): Five female rhesus monkeys exposed prenatally to T propionate and six normal females underwent blood sampling immediately before and 24 h after a 200-IU IM injection of recombinant hCG. MAIN OUTCOME MEASURE(S): Serum T, 17alpha-hydroxyprogesterone, DHEAS, and cortisol concentrations determined by RIA. RESULT(S): Prenatally androgenized females exhibited increased T and 17alpha hydroxyprogesterone response to recombinant hCG stimulation, compared to control females. Although serum adrenal DHEAS concentrations were elevated in comparison to control females, the increased levels of DHEAS were not dependent on recombinant hCG stimulation. CONCLUSION(S): Prenatal androgen excess in female rhesus monkeys causes perturbations in ovarian and adrenal steroidogenesis during adulthood, which may both contribute to hyperandrogenism. PMID- 11779610 TI - A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility. AB - OBJECTIVE: To test the hypothesis that, in couples with unexplained infertility, tubal flushing with an oil-soluble media (lipiodol) would increase the pregnancy rate within 6 months compared with expectant management. DESIGN: A prospective, randomized, controlled study in which couples were allocated to either a single treatment with lipiodol or no further action. SETTING: Two tertiary referral centers for assisted reproduction. PATIENT(S): Couples with a diagnosis of primary or secondary unexplained infertility based on a normal semen analysis according to World Health Organization criteria, patent fallopian tubes at hysterosalpingography or laparoscopy, and ovulatory menstrual cycles based on midluteal phase progesterone levels or ultrasonic follicle tracking. INTERVENTION(S): In those patients randomized to lipiodol, a single treatment was performed. MAIN OUTCOME MEASURE(S): Biochemical (i.e., positive pregnancy test) and clinical (i.e., fetal heart on ultrasound scan) pregnancy rates. RESULT(S): Seventeen couples were randomized to lipiodol and 17 to expectant treatment. The higher pregnancy rate after lipiodol was statistically significant. There were no complications after lipiodol treatment. CONCLUSION(S): There was a statistically significantly higher pregnancy rate in couples with unexplained infertility randomized to a single tubal flush with lipiodol compared with no treatment. PMID- 11779611 TI - A uterine wall defect after uterine artery embolization for symptomatic myomas. PMID- 11779612 TI - Primary infertility associated with isolated cervical collecting diverticulum. AB - OBJECTIVE: To describe a previously unreported isolated congenital cervical diverticulum and its gynecologic, reproductive, and obstetrical implications. DESIGN: Case report. SETTING: A university hospital. PATIENT: A 31-year-old woman presenting with menometrorrhagia and primary infertility. Investigation revealed an isolated collecting cervical diverticulum causing prolonged postmenstrual spotting, possibly interfering with sperm capacitation and access to the uterine cavity. INTERVENTION(S): The examination included hysterosalpingography and magnetic resonance imaging. The combined hysteroscopy and laparoscopy revealed a 5 x 5 cm cervical diverticulum, around 1 cm from the external cervical os, leading to a short cervical canal connected to a normal uterine cavity. The patient achieved a pregnancy after controlled ovarian hyperstimulation and ultrasonographically guided intrauterine insemination. MAIN OTUCOME MEASURE(S): Pregnancy and obstetrical outcome. RESULT(S): Extensive evaluation revealed the patient's condition to be a previously undescribed congenital cervical anomaly. The patient's infertility was corrected by ovulation induction and sonographically guided intrauterine insemination, which resulted in a twin pregnancy. After 27 weeks of gestation, preterm labor complicated the delivery. CONCLUSION(S): The diagnosis and management of this unusual congenital cervical diverticulum present a particular challenge, as this congenital abnormality has not been previously described or reported. PMID- 11779614 TI - Gonadal agenesis 46,XX associated with the atypical form of Rokitansky syndrome. AB - OBJECTIVE: To describe a patient with bilateral ovarian agenesis associated with the atypical form of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: Case report. SETTING: Unit of Endocrinology, Fundacion Hospital Alcorcon. Madrid (Spain). PATIENT: A 17-year-old woman who presented with primary amenorrhea and lack of mammary development. INTERVENTION(S): An endocrine study including pituitary, ovarian, adrenal, and thyroid evaluation was performed. Genetic study was done by karyotype and fluorescence in situ hybridization (FISH) analysis to detect the presence of Y chromosome material. Bone study, intravenous urography, pelvic ultrasound, and laparoscopic study were ordered to evaluate the associated genitourinary and skeletal anomalies. MAIN OUTCOME MEASURE(S): Anatomic, endocrine, and genetic description of the patient. RESULT(S): The gynecologic examination showed a normal vagina ending in a blind pouch. The endocrine evaluation disclosed gonadotropin levels in the menopausal range and nonautoimmune subclinical primary hypothyroidism. The laparoscopic study revealed a single pelvic kidney and an absence of gonads, fallopian tubes, and uterus. The karyotype was 46,XX; no Y chromosome was found in FISH analysis. CONCLUSION(S): To our knowledge, this is the first report of gonadal agenesis 46,XX associated with the atypical form of MRKH syndrome. The primary hypothyroidism may be coincidental. PMID- 11779613 TI - Evidence of early placental vascular anastomosis during selective embryo reduction in monozygotic twins. AB - OBJECTIVE: To describe selective embryo reduction of two triplet pregnancies with a monozygotic twin. DESIGN: Case reports. SETTING: Infertility unit of a Department of Obstetrics and Gynecology. PATIENT(S): Two patients treated with IVF-ET who had triplet pregnancies. INTERVENTION(S): Selective embryo reduction of monozygotic twins. MAIN OUTCOME MEASURE(S): Fetal heart beat. RESULT(S): During intracardiac injection of potassium chloride plus midazolam in one of the monozygotic twin fetuses, we observed an immediate diminution of the cardiac pulse rate of the second twin. This phenomenon was observed in both patients. CONCLUSION(S): These observations clearly indicate the presence of vascular anastomosis between the two fetuses of these monozygotic twins. Thus, use of toxic substance to reduce one of the two fetuses of a monozygotic twin pregnancy is contraindicated. In cases of triplets that include a monozygotic twin, it is safest to interrupt the evolution of the twin if selective reduction is desired. PMID- 11779615 TI - Two successful pregnancies after conservative treatment of endometrial cancer and assisted reproduction. AB - OBJECTIVE: To report successful pregnancies after conservative management of FIGO grade I adenocarcinoma of the endometrium. DESIGN: Retrospective chart review. SETTING: University-based assisted reproduction and oncology units. PATIENT(S): One patient who had two separate pregnancies. INTERVENTION(S): High-dose progestin (megestrol acetate) therapy for adenocarcinoma, followed by assisted reproduction with donor oocyte. MAIN OUTCOME MEASURE(S): Histologic evaluation of endometrium after megestrol acetate and at completion of childbearing, and successful pregnancies and deliveries. RESULT(S): The patient had complete resolution of adenocarcinoma with progestin therapy and successful delivery of two pregnancies after assisted reproduction. CONCLUSION(S): Conservative management of International Federation of Gynecology and Obstetrics grade I adenocarcinoma of the endometrium allows preservation of childbearing. PMID- 11779617 TI - Pilot study of racial differences and longitudinal changes in inhibin B in the late reproductive years. PMID- 11779616 TI - Results of assisted reproductive technologies in patients with endometriosis. PMID- 11779618 TI - Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer. PMID- 11779619 TI - Ethical differences between sex selection by sperm and embryo? PMID- 11779621 TI - Turned, twisted and torqued?--management. PMID- 11779624 TI - Transient dynamics and pattern formation: reactivity is necessary for Turing instabilities. AB - The theory of spatial pattern formation via Turing bifurcations - wherein an equilibrium of a nonlinear system is asymptotically stable in the absence of dispersal but unstable in the presence of dispersal - plays an important role in biology, chemistry and physics. It is an asymptotic theory, concerned with the long-term behavior of perturbations. In contrast, the concept of reactivity describes the short-term transient behavior of perturbations to an asymptotically stable equilibrium. In this article we show that there is a connection between these two seemingly disparate concepts. In particular, we show that reactivity is necessary for Turing instability in multispecies systems of reaction-diffusion equations, integrodifference equations, coupled map lattices, and systems of ordinary differential equations. PMID- 11779625 TI - Testing goodness of fit for stochastic models of carcinogenesis. AB - This paper considers the utility of statistical goodness of fit testing in the context of mechanistic models of carcinogenesis. Two stochastic models of carcinogenesis were tested with several sets of experimental and epidemiological data using a formal goodness of fit test specially designed to accommodate censored observations: these were the two-stage model allowing for clonal expansion of initiated cells and its simpler version with gamma distributed promotion time. The results of this application, supplemented by visual examination of local likelihood kernel estimates of the hazard function and the corresponding model-based estimates, show that mechanistic models of carcinogenesis provide a good fit to the data in the majority of cases under study. PMID- 11779626 TI - Habitat edges and predator-prey interactions: effects on critical patch size. AB - We use partial differential equation models to examine the effects of cross-edge incursions by a predator on the persistence or extinction of a patch-resident prey species. For each of two predator-incursion profiles (namely, a constant incursion distance and a constant loss rate for predators during incursions), we examine the conditions under which the predator can (and cannot) influence the critical patch size of a prey species. PMID- 11779627 TI - Detection of hormesis effect in longevity: simulation approach for heterogeneous population. AB - Manifestation of hormesis in longevity was modelled by modification of the mortality rate during and after the period of a stress factor action. In heterogeneous population this can lead to observation of unchanged mortality during action of the stress and decrease in mortality after stress period. Stochastic simulations were made to investigate the possibility of detecting the hormesis effect on the basis of the stress-control longitudinal data. The goal of the stochastic simulation was to investigate the role in the hormesis detection of control and stressed group size, of population heterogeneity variance value, of stress and hormesis attributable risks as well as the role of a prior information about the survival in the control group. It was demonstrated that if the attributable risks for stress and hormesis effects are approximately equal, then in both 'high' and 'low' heterogeneous populations the hormesis phenomenon is detected with probability higher than 75% even in relatively 'small' groups of 50 subjects. In case of 'weak' effect the hormesis phenomenon is not detected in a 'highly heterogeneous' population even in a group composed of 1000 subjects. In a 'low heterogeneous' population the hormesis phenomenon is detected with probability higher than 70% when the group size is not less than 200 subjects. Information about the survival in control group did not play a critical role in all experiments and exact survival curve may be replaced by the traditional Kaplan-Meier estimate. PMID- 11779628 TI - Rice (Oryza sativa) contains a novel isoform of glutamate decarboxylase that lacks an authentic calmodulin-binding domain at the C-terminus. AB - We have isolated full-length cDNAs for two distinct isoforms of glutamate decarboxylase (GAD), designated OsGAD1 and OsGAD2 from a rice shoot cDNA library. Open reading frames found in OsGAD1 and OsGAD2 cDNAs encode putative proteins of 501 (56.7 kDa) and 500 amino acids (55.6 kDa), respectively. They show 69% identity to each other and 67-78% identity to dicotyledonous counterpart sequences determined so far. Comparative analysis of relevant genomic clones obtained from the rice genomic library with these cDNAs as probes demonstrated that the number and sizes of introns deduced for these two genes differ considerably. Interestingly, in the regions in the putative gene products corresponding to the C-terminal 30-amino-acid peptide known as the calmodulin binding domain of plant GADs, OsGAD1 possesses a typical motif, while OsGAD2 contains several substitutions of amino acids that contribute strongly to the binding of calmodulin (CaM). An in vitro CaM-binding assay of these proteins over expressed in Escherichia coli revealed that OsGAD1 can in fact bind specifically to bovine CaM but OsGAD2 cannot. RNA analysis showed that transcripts of OsGAD1 and OsGAD2 were present in all tissues examined, but their expression was differentially regulated, at least in roots and maturing seeds. PMID- 11779629 TI - Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli. AB - There are two isochorismate synthase genes entC and menF in Escherichia coli. They encode enzymes (isochorismate synthase, EC 5.4.99.6) which reversibly synthesize isochorismic acid from chorismic acid. The genes share a 24.2% identity but are differently regulated. Activity of the MenF isochorismate synthase is significantly increased under anaerobic conditions whereas the activity of the EntC isochorismate synthase is greatly stimulated during growth in an iron deficient medium. Isochorismic acid synthesized by EntC is mainly channeled into enterobactin synthesis whereas isochorismic acid synthesized by MenF is mainly channeled into menaquinone synthesis. When menF or entC were separately placed onto overexpression plasmids and the plasmids introduced into a menF(-)/entC(-) double mutant in two separate experiments, the isochorismate formed was fed into both, the menaquinone and the enterobactin pathway. Moreover, in spite of a high isochorismate synthase activity menaquinone and enterobactin formation were not fully restored, indicating that isochorismate was lost by diffusion. Thus, under these conditions channeling was not observed. We conclude that in E. coli the chromosomal position of both menF and entC in their respective clusters is a prerequisite for channeling of isochorismate in both pathways. PMID- 11779630 TI - Leaving group stabilization by metal ion coordination and hydrogen bond donation is an evolutionarily conserved feature of group I introns. AB - To understand the behavior of group I introns on a biologically fundamental level, we must distinguish those traits that arise as the products of natural selection (selected traits) from those that arise as the products of neutral drift (non-selected traits). In practice, this distinction relies on comparing the similarities and differences among widely divergent introns to identify conserved traits. Here we address whether the strategies used by the eukaryotic group I intron from the Tetrahymena ciliate to stabilize the leaving group during splicing are maintained in the group I intron from the widely divergent Azoarcus bacterium. A substrate analogue containing a 3'-phosphorothiolate linkage, in which a sulfur atom replaces the bridging 3'-oxygen atom of the scissile phosphate, reacts 20-fold slower in the Azoarcus reaction than the corresponding unmodified substrate in the presence of Mg(II) as the only divalent cation. However, Mn(II) relieves this negative effect such that the 3'-S-P bond cleaves 21-fold faster than does the 3'O-P bond. Other thiophilic divalent metal ions such as Co(II), Cd(II), and Zn(II) similarly support cleavage of the S-P bond. These results indicate that a metal ion directly coordinates to the leaving group in the transition state of the Azoarcus ribozyme reaction. Additionally, the 3' sulfur substitution eliminates the approximately 10(3)-fold contribution of the adjacent 2'-OH to transition state stabilization. Considering that sulfur accepts hydrogen bonds weakly compared to oxygen, this result suggests that the 2'-OH contributes to catalysis by donating a hydrogen bond to the 3'-oxygen leaving group in the transition state, presumably acting in conjunction with the metal ion to stabilize the developing negative charge. These same catalytic strategies of metal ion coordination and hydrogen bond donation operate in the Tetrahymena ribozyme reaction, suggesting that these features of catalysis have been conserved during evolution and thus extend to all group I introns. The two ribozymes also exhibit quantitative differences in their response to 3'-sulfur substitution. The Azoarcus ribozyme binds and cleaves the phosphorothiolate substrate more efficiently relative to the natural substrate than the Tetrahymena ribozyme under the same conditions, suggesting that the Azoarcus ribozyme better accommodates the phosphorothiolate at the active site both in the ground state and in the transition state. These differences may reflect either a less tightly knit Azoarcus structure and/or spatial deviations between backbone atoms in the two ribozymes that arise during divergent evolution, analogous to the well documented relationship between protein sequence and structure. PMID- 11779631 TI - Identification of a novel retina-specific gene located in a subtelomeric region with polymorphic distribution among multiple human chromosomes. AB - The human retina is comprised of a large number of cell types with highly specialized functions that depend on the action of countless genes, many of which are exclusively expressed in the retina. We have isolated a novel retinal gene, termed F379. The transcript was initially identified as a cluster of ESTs derived predominantly from retinal cDNA libraries and its retinal transcription confirmed by Northern blot and RT-PCR. Screening of retinal cDNA libraries yielded four clones that were assembled into a 1188 bp consensus sequence. The putative open reading frame includes an unusual configuration of Alu and MIR repeats and encodes a putative 85 aa peptide with no significant homology to any known protein sequence outside of the Alu and MIR elements. Comparison with genomic sequence determined that F379 consists of three exons and maps to multiple locations throughout the genome, a finding confirmed by PCR screening of a somatic cell hybrid mapping panel. F379 appears to be contained within a region of subtelomeric DNA that is duplicated in a polymorphic distribution to multiple chromosomes. Comparison of interchromosomal sequence variation with the sequences of expressed transcripts suggests that the gene is transcribed in the human retina from at least four different chromosomes. PMID- 11779632 TI - The modulation of the biological activities of mitochondrial histone Abf2p by yeast PKA and its possible role in the regulation of mitochondrial DNA content during glucose repression. AB - The mitochondrial histone, Abf2p, of Saccharomyces cerevisiae is essential for the maintenance of mitochondrial DNA (mtDNA) and appears to play an important role in the recombination and copy number determination of mtDNA. Abf2p, encoded by a nuclear gene, is a member of HMG1 DNA-binding protein family and has two HMG1-Box domains, HMG1-Box A and B. To investigate the role of Abf2p in the control of mtDNA copy number, we asked if the in vivo functions of Abf2p are regulated by the possible modification such as phosphorylation. We found that the N-terminal extended segment (KRPT(21)S(22)) of HMG1-Box A is rapidly and specifically phosphorylated by cAMP-dependent protein kinase (PKA) in vitro. The phosphorylation in this region inhibits the binding of Abf2p to all kinds of DNA including four-way junction DNA and the supercoiling activity of Abf2p itself. The abf2 mutant cells with an abf2(T21A/S22A) allele defective in the phosphorylation site have a severe defect in the regulation of mtDNA content during glucose repression in vivo. These observations suggest that the phosphorylation via PKA, that is activated during glucose repression, may regulate the in vivo functions of Abf2p for the control of mtDNA content during shift from gluconeogenic to fermentative growth. PMID- 11779633 TI - Differential expression of the whey acidic protein gene during lactation in the brushtail possum (Trichosurus vulpecula). AB - The whey acidic protein (WAP) is a whey protein found in the milk of a number of species. We have isolated and characterised a WAP cDNA clone from the brushtail possum (Trichosurus vulpecula) and examined its expression in the mammary gland. The amino acid sequences of WAP from the possum and another marsupial, the tammar wallaby, share 69% identity, however, less sequence identity exists between the marsupial and eutherian WAP sequences (30-37%). The possum and tammar WAP genes consist of three four-disulphide core (4-DSC) domains, with a WAP motif at the beginning of each domain. In contrast, the eutherian WAP sequences consist of two 4-DSC domains with the WAP motif only present in the second domain. This WAP motif is also present in a number of protease inhibitors found in a wide range of species. Phylogenetic analysis of marsupial and eutherian WAP sequences suggests that the ancestral WAP gene has three domains and that one of the domains has been deleted from the eutherian gene. The profile of WAP gene expression in the possum mammary gland changed throughout lactation, with WAP mRNA levels reaching a peak between days 106 and 177 of lactation. The level of WAP mRNA in the mammary gland appeared to be correlated with the level of circulating prolactin in the lactating female and was different to that observed for several other whey protein genes. Overlapping expression of the WAP and early lactation protein genes, both of which are putative protease inhibitors, may provide protection of milk immunoglobulins that are required for the prolonged period of passive immune transfer to the marsupial pouch young. PMID- 11779634 TI - The transcription factors Sp1 and Sp3 are required for human angiotensin II type 1 receptor gene expression in H295-R cells. AB - The peptide hormone angiotensin II regulates a variety of physiological responses which are mediated by its interaction with high affinity G protein-coupled receptors localized on the surface of target cells. Our previous studies have demonstrated that a 145 bp sequence within the promoter region was required for basal level expression of the human angiotensin II type 1 receptor (hAT(1)R) gene. In the present study, deletional analysis of the hAT(1)R promoter localized the major regulatory sequence to two overlapping GC boxes harbored within the 105 to -85 bp region relative to the transcription start site in H295-R cells. Electrophoretic mobility shift assays (EMSAs) using a double-stranded (ds) oligonucleotide corresponding to this region and H295-R cell nuclear extract resulted in five specific DNA-protein complexes. EMSAs performed with competitive ds-oligonucleotides which harbored the consensus binding site for Sp1 prevented the formation of the DNA-protein complexes. Supershift EMSAs also demonstrated that Sp1 and Sp3 could bind to the GC boxes present within the -105 to -85 bp region of the hAT(1)R promoter. Transactivation experiments utilizing Drosophila SL2 cells, which lack endogenous Sp family transcription factors, demonstrated that Sp1 and Sp3 activated the hAT(1)R promoter and that maximal activation was only achieved when both GC boxes were present. Taken together, these findings suggest that Sp1 and Sp3 are necessary for the expression of the hAT(1)R gene in H295-R cells. PMID- 11779635 TI - Genomic structure and regulation of a novel human gene, Klp1. AB - Klp1 (K562 cells-derived leucine zipper-like protein 1) is a transcription factor which binds to the coproporphyrinogen oxidase promoter regulatory element (GGACTACAG). In order to clarify the function of Klp1, we determined the complete human Klp1 genomic structure and regulatory element in the promoter region. The gene spans about 2.4 kb and has three exons. Its promoter region has multiple GC boxes, E2F binding site, one cAMP response element (CRE), and no TATA box with multiple transcription initiation sites, which is characteristic of housekeeping and growth regulating genes. Promoter analysis showed that the promoter was more active in K562 cells entered into the cell cycle by serum stimulation than quiescent cells. Further promoter analysis revealed that CRE at -42 is essential for full promoter activity, and c-Jun and activation transcription factor 1/cAMP response element binding protein 1 proteins bind to this element. These structural characteristics and the promoter function suggest that Klp1 may play a role in cell cycle regulation. PMID- 11779636 TI - A glutathione S-transferase cDNA identified by mRNA differential display is upregulated during somatic embryogenesis in Cichorium. AB - CHI-GST1, a cDNA encoding a glutathione S-transferase, was isolated by differential display in leaf tissues of chicory, during the early stages of somatic embryogenesis. Expression analysis of the gene by Northern blot indicated that the transcript accumulation is specific of the leaf developing somatic embryogenesis and is not observed in leaf tissue of the non-embryogenic cultivar. PMID- 11779637 TI - cDNA cloning and expression of mutant catalase from the hypocatalasemic mouse: comparison with the acatalasemic mutant. AB - Mutant catalase cDNAs from the hypocatalasemic and acatalasemic mice were cloned and expressed in bacteria. A novel missense mutation, Asp (AAT) to Ser (AGT), was identified at amino acid position 439 of the hypocatalasemic catalase. Analysis of recombinant catalase mutants revealed that the mutation is responsible for the reduced activity of hypocatalasemic catalase and the unstable tetrameric structure of acatalasemic catalase was also suggested. PMID- 11779638 TI - Characterization of ADAMTS14, a novel member of the ADAMTS metalloproteinase family. AB - ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) proteins constitute a family of zinc metalloproteinases which target and process extracellular matrix proteins. We cloned and characterized a novel human ADAMTS gene, ADAMTS14, which is located on human chromosome 10q2. ADAMTS14 exhibits the characteristic multidomain structure of ADAMTS proteins including four thrombospondin modules and shows highest similarity to ADAMTS3 and ADAMTS2. By RT-PCR analysis we demonstrated that ADAMTS14 is expressed in human retina and also at low levels in adult brain, lung and placenta. PMID- 11779639 TI - Functional analysis of diploid wheat rRNA promoter by transient expression. AB - The rRNA gene promoter regions of three diploid wheats Triticum boeoticum Boiss, Triticum urartu Tum. ex Gandil, and Triticum monococcum L. have been sequenced and analyzed. It has been found that the rRNA promoter initiation regions of diploid wheats contain the sequences, which differ from the evolutionary conserved TATAGTAGG (+1 is underlined) motif of monocots. The transient expression assay in wheat protoplasts confirmed that cloned sequences are active promoters. Deletion analysis showed that the promoter sequence localized between 113 and +15 (relative to +1) is enough to direct RNA polymerase I-dependent transcription. PMID- 11779640 TI - Nucleotide sequence and cell cycle-associated differential expression of ZF5128, a novel Kruppel type zinc finger protein gene. AB - The nucleotide sequence of the ZF5128 gene, encoding a novel Kruppel type zinc finger protein, has been determined. The ZF5128 gene has a predicted 553-amino acid open reading frame, encoding a putative 61 kDa zinc finger protein. The N terminus of the ZF5128 coding region has a well-conserved Kruppel-associated box (KRAB) domain that consists of KRAB box A and B, whereas the C-terminus contains a Kruppel type C2H2 zinc finger domain possessing nine C2H2 zinc finger motifs in tandem arrays with the highly conserved space region of the H/C-link. Each C2H2 zinc finger motif has a typical consensus sequence of CX2CX3FX5LX2HX3H. A 3.2 kb transcript specific for ZF5128 was expressed at high levels in the spleen, thymus, and peripheral blood leukocyte, and weakly expressed in the prostate, ovary, small intestine, colon (mucosal lining), placenta, lung, and pancreas. Although there was no detectable ZF5128 mRNA in unstimulated human peripheral T cells, it was first detectable 1.5 h after activation by anti-CD3 plus anti-CD28, and reached a maximum in 25-30 h. During the cell cycle progression of Jurkat T cells, the expression of ZF5128 mRNA appeared to be induced in G1 and reached a maximum in the S phase, but declined as the cells entered the G2/M phase. The 12 O-tetradecanoylphorbol 13-acetate-induced monocytic differentiation of U937, which also resulted in growth arrest, down-regulated the expression of ZF5128 mRNA. Taken together, these results indicate that ZF5128 is a novel gene encoding a Kruppel type C2H2 zinc finger protein and is regulated at the transcriptional level depending on tissue type and the cell cycle status to support cell proliferation. PMID- 11779642 TI - Biomechanics of the cervical spine 4: major injuries. AB - This review presents considerations regarding major cervical spine injury, including some concepts that are presently undergoing evaluation and clarification. Correlation of certain biomechanical parameters and clinical factors associated with the causation and occurrence of traumatic cervical spine injuries assists in clarifying the pathogenesis and treatment of this diverse group of injuries. Instability of the cervical column based on clinical and mechanistic perspectives as well as the role of ligaments in determining instability is discussed. Patient variables such as pre-existing conditions (degenerative disease) and age that can influence the susceptibility or resistance to injury are reviewed. Radiological considerations of major injuries including dynamic films, CT and MRI are presented in the diagnosis and treatment of cervical trauma. Specific injury patterns of the cervical vertebral column are described including attention to the relative mechanisms of trauma. From a biomechanical perspective, quantification of injury tolerance is discussed in terms of external and human-related variables using laboratory-driven experimental models. This includes force vectors (type, magnitude, direction) responsible for injury causation, as well as potential influences of loading rate, gender, age, and type of injury. PMID- 11779641 TI - Differential expression of adipose- and heart-type fatty acid binding proteins in hibernating ground squirrels. AB - The up-regulation of heart- and adipose-type fatty acid binding proteins (H-FABPs and A-FABPs) was detected during hibernation in brown adipose tissue (BAT) of 13 lined ground squirrels, Spermophilus tridecemlineatus, using a commercial rat cDNA array. Full length cDNAs encoding H-FABPs and A-FABPs were subsequently retrieved from a BAT cDNA library. These cDNAs were used to probe Northern blots of total RNA from tissues of euthermic versus hibernating ground squirrels. H FABP mRNA transcripts increased in BAT, skeletal muscle and heart of hibernating animals whereas A-FABP transcripts, which are normally expressed exclusively in adipose tissue, increased in both BAT and heart during torpor. It is proposed that the increased expression of H-FABPs and A-FABPs during hibernation accelerates the rate at which fatty acids can be transported to the mitochondria for oxidization, particularly in support of the huge increase in thermogenesis by BAT and rapid increase in heart rate that are required during arousal from torpor. Comparison of the deduced polypeptide sequence of ground squirrel H-FABP with that from other mammals also revealed three unique amino acid differences which may be important for protein function at low body temperatures during hibernation. PMID- 11779643 TI - Sagittal plane segmental motion of the cervical spine. A new precision measurement protocol and normal motion data of healthy adults. AB - OBJECTIVE: (1) Precise documentation of sagittal plane segmental rotational and posteroanterior translational motion of segments C0/C1-C6/C7 of the human cervical spine from lateral radiographic views. (2) Compilation of a database describing normal motion. (3) Comparison of individual motion patterns with the normal database. DESIGN: Descriptive study based on computer-aided measurements from lateral radiographic views taken in flexion and extension. BACKGROUND: Previous studies concentrated on segmental rotational motion of the cervical spine. Normal data for translational motion were not available. Description of cervical spine motion patterns thus remained incomplete. METHODS: Based on computer-aided measurements from lateral radiographic views taken in flexion and extension, a new protocol determines rotational and translational motion for all segments (C0/C1-C6/C7) imaged on the radiographic views. Measured results are corrected for radiographic magnification and variation in stature; they are virtually uninfluenced by radiographic distortion and patient alignment errors. A database describing normal motion was compiled from 137 sets of lateral views of healthy adults taken in active flexion and extension. A specimen study as well as inter- and intra-observer studies quantify measurement errors. RESULTS: The error study demonstrated the error (SD) of a rotational motion measurement to amount to slightly less than 2 degrees. The error (SD) of a translational motion measurement amounts to less than 5% of vertebral depth; for a vertebra of 15 mm depth this corresponds to 0.7 mm. A normal database for rotational and translational motion was compiled. There was a linear relation between rotational and translational motion. This finding agrees qualitatively with results from previous studies; quantitative comparisons are not possible due to divergent definitions for translational motion. The relation between rotation and translation can be employed in individual cases to predict translational motion, in dependence on the rotation actually performed. A comparison of the rotational motion with the normal database and the difference between predicted and actual translational motion allow segmental hypo-, normal or hypermobility to be quantified. CONCLUSIONS: The new protocol measures segmental motion with high precision and corrects for radiographic distortion, variation in stature and alignment errors of patients. Thus, archive studies using existing radiographs are feasible. RELEVANCE: Flexion-extension radiographs of the cervical spine are performed to explore potential damage to the bony or ligamentous structure resulting in abnormal, segmental motion patterns. Determining rotational motion gives only an incomplete picture. The new protocol allows for precise quantification of translational motion and classification of segments as hypo- or hypermobile by comparison with normal motion data. PMID- 11779644 TI - Effects of acetabular component orientation on dislocation propensity for small head-size total hip arthroplasty. AB - OBJECTIVE: Examine the role of surgical orientation of the acetabular cup on posterior dislocation propensity for small-head-size total hip arthroplasty. DESIGN: A finite element model of a widely used total hip arthroplasty system was examined for peak resisting moment and range-of-motion prior to impingement, as well as prior to onset of posterior dislocation. Acetabular component surgical orientation was varied. BACKGROUND: Dislocation is a leading cause of total hip replacement failure, with an incidence between 2% and 11%. Clinical registries imply acetabular component orientation to be a leading predictor of dislocation. The finite element method permits this complex kinetic behavior to be addressed systematically. METHODS: Twenty-five combinations of cup abduction (five angles) and anteversion (five angles) were studied, with the resultant resisting moment about the cup center being tracked in each case. Key events were benchmarked, and a novel dislocation resistance index was developed for multi-factor comparison. RESULTS: Increasing tilt and/or anteversion resulted in a monotonically increasing range-of-motion prior to impingement, as well as increased peak resisting moment. Range of motion was more sensitive to tilt, while peak resisting moment was more sensitive to anteversion. Peak resisting moment for 22 mm head size was nearly 25% less than that for a 26-mm head. CONCLUSIONS: Increased cup tilt and anteversion discourage posterior dislocations of small head-size components. RELEVANCE: Pre-existing soft tissue compromise and untoward patient motions/postures are largely beyond surgeon control. However, other factors being equal, especially for small-head-size components, many posterior dislocations that would otherwise occur might be prevented by suitable tilt and anteversion of the acetabular component. PMID- 11779645 TI - Modelling debonded stem-cement interface for hip implants: effect of residual stresses. AB - OBJECTIVE: To assess the effect of the residual stresses due to cement curing on the load transfer of cemented hip implants. DESIGN: The load transfer at the stem cement interface of an idealized hip stem surrounded by cortical bone was investigated using a three-dimensional finite element analysis. A debonded stem cement interface was considered to simulate a highly polished stem in contact with cement; Coulomb friction at the stem-cement interface was considered. BACKGROUND: Numerical analyses on the load transfer of cemented hip implants do not include residual stresses due to cement curing at the stem-cement interface. METHODS: The magnitude of the residual stresses was determined experimentally. In the finite element model, non-linear contact elements modelled the debonded stem cement interface. In particular, the compressive radial residual stresses that are generated at the interface, due to the cement expansion during curing, were treated similar to a press-fit problem. RESULTS: The cement stress distributions were affected by the magnitude of the residual stresses. Failing to include residual stresses underestimated the cement stresses at the interface, mainly affecting the radial and hoop stresses. The load was transferred from the stem to the cement more uniformly along the interface once residual stresses were included. CONCLUSIONS: Because there is no chemical bond at the interface between the stem and cement, the interface resistance depends on friction thus radial residual compressive stresses developed by the cement curing play a direct role. RELEVANCE: Implant loosening of cemented hip implants is one of the major causes of late failure of the arthroplasty. The load is transferred from the stem to the bone primarily across the interfaces, consequently modelling accurately the interface is essential in predicting the load transfer. PMID- 11779646 TI - Relative motion of a mobile bearing inlay after total knee arthroplasty--dynamic in vitro study. AB - OBJECTIVE: The purpose of this study was to measure the in vitro range of motion of a mobile bearing inlay knee prosthesis under dynamic isokinetic loading conditions. Additionally, the effect on the range of motion of rotational malalignment of the tibia baseplate was determined. DESIGN: Specimens with implanted knee prostheses were mounted onto a custom built knee simulator. 3-D inlay movement was measured by an ultrasonic tracking system. BACKGROUND: More recent knee prostheses include mobile bearing inlays type designs. These systems are intended to allow higher conformity of the tibiofemoral joint and thereby decrease contact stress without decreasing the knee's range of motion. METHODS: Dynamic testing in the knee simulator mimicked both the speed and resulting moment of a knee isokinetic extension test. The tibia baseplate was first implanted with no rotational malalignment, followed by sequential internal and external rotation of upto 15 degrees. RESULTS: Correctly aligned, the inlay center moved 3.5 mm (SD, 1.5 mm) posterior during extension. With the tibia baseplate externally rotated more than 10 degrees the movement pattern changed. CONCLUSION: At up to 10 degrees of rotational malalignment the primary motion pattern of the mobile bearing is maintained. However, beyond 10 degrees unintended motion may occur. RELEVANCE: These test results correlate to radiographic measurements of in vivo movements of mobile bearing inlays showing "paradoxical" movement of the mobile inlay compared to physiologic meniscal movement. PMID- 11779647 TI - The effect of insufficient quadriceps strength on gait after anterior cruciate ligament reconstruction. AB - OBJECTIVE: To determine the effect of quadriceps strength and joint stability on gait patterns after anterior cruciate ligament injury and reconstruction. DESIGN: Cross-sectional comparative study in which four groups underwent motion analysis with surface electromyography. BACKGROUND: Individuals following anterior cruciate ligament rupture often demonstrate reduced knee angles and moments during the early stance phase of gait. Alterations in gait can neither be ascribed to instability nor to quadriceps weakness alone when both are present. METHODS: Twenty-eight individuals with complete anterior cruciate ligament rupture (10 patients with acute rupture, 8 patients following reconstruction with quadriceps strength >90% of the uninvolved side [strong-anterior cruciate ligament reconstructed group], and 10 patients after reconstruction with quadriceps strength <80% of the uninvolved side [weak-anterior cruciate ligament reconstructed group]), and 10 uninjured subjects underwent an examination of their lower extremity to collect kinematics, kinetics, and electromyography during walking and jogging. Anterior cruciate ligament reconstruction was arthroscopically assisted and a double loop semitendinosis-gracilis autograft or allograft was used as a graft source. All reconstructed subjects had stable knees, full range of motion, and no effusion or pain at the time of testing (more than three months after surgery). RESULTS: Knee angles and moments of the strong group were indistinguishable from the uninjured group during early stance of both walking and jogging. The weak subjects had reduced knee angles and moments during walking, and jogged similarly to the deficient subjects. Regression analysis revealed a significant effect between early stance phase knee angles and moments and quadriceps strength during both walking and jogging. CONCLUSION: Inadequate quadriceps strength contributes to altered gait patterns following anterior cruciate ligament reconstruction. RELEVANCE: Rapid strengthening following anterior cruciate ligament injury or reconstruction may contribute to a safe return to high-level activities. PMID- 11779648 TI - Mechanical conditions in the internal stabilization of proximal tibial defects. AB - OBJECTIVES: The goal was to design a method which would permit an assessment of the suitability of a newly developed implant under physiological-like loading conditions. Information obtained from such an analysis is expected to delineate more clearly the indications for a new device prior to clinical utilization. DESIGN: In vitro mechanical stiffness testing and finite element analysis. METHODS: From in vitro testing of proximal tibiae with defects, the stiffness of an internal stabilization system was determined. Using a finite element model, the loading of both the implant and bone was analyzed including all muscle forces. The variation in implant loading and interfragmentary strain for different defect locations was also investigated. RESULTS: Conventional stiffness testing demonstrated the comparability of the experimental findings with the finite element predictions. Under physiological-like loading the implant experienced high bending and von Mises stresses if defects in the region of the shaft were stabilized. A short working length increased implant loading up to the yield strength of the material. CONCLUSIONS: The finite element analysis illustrated the appropriateness of this new device for proximal defects of the tibia, but the implant should be used with hesitation in fractures or defects extending into the diaphyseal region of the bone. RELEVANCE: This new analytical approach helped to identify clinical indications for the implant in which its mechanical attributes would prove advantageous. PMID- 11779649 TI - Surface fissures in articular cartilage: new concepts, hypotheses and modeling. AB - OBJECTIVE: Clarification and mesomechanical modeling of the inception of fissures at the surface of articular cartilage. DESIGN: Articular cartilage is described as a macroscopically heterogeneous medium consisting of zones - layers - with different orientation of collagen fibers. BACKGROUND: Degradation of mechanical properties of cartilage is a serious, still not fully clarified problem that deserves attention. METHODS: Theoretical analysis based on a survey of known experimental findings related to the subject. The general author's mesomechanical concept of modeling heterogeneous media is applied to the elucidation and description of the formation of fissures at the surface of articular cartilage. RESULTS: Our model clarifies how the high tensile stresses in the collagen fibers of the superficial tangential zone depend on the rate of loading. CONCLUSIONS: The superficial cracks are caused predominantly by a very quick loading. This explains among others the high incidence of post-traumatic osteoarthritis of the lower extremity after accidents and injuries in sports. RELEVANCE: Superficial fissures in articular cartilage are observed in joints with primary osteoarthritis. The current study specifies the kinds of loading that lead to their inception. PMID- 11779651 TI - Eimeria infections in cows in the periparturient phase and their calves: oocyst excretion and levels of specific serum and colostrum antibodies. AB - Faecal Eimeria oocyst excretion and levels of antibodies to first generation merozoite antigen of E. bovis in sera and colostra were followed in 86 and 70 cow calf pairs in northern (group EF) and central Germany (group H), respectively, over periods of 3 weeks before to 3 weeks after calving in cows and from birth to an age of 63 days in calves. Oocysts were found in 30 and 7.7% of cows in groups EF and H, respectively. They belonged to 10 (group EF) and four Eimeria spp. (group H) with E. bovis, E. ellipsoidalis, E. auburnensis and E. zuerni as the most frequently occurring species. Prevalence and intensity of oocyst excretion varied with time resulting in peak values around the date of parturition, particularly in the case of E. bovis. Peak values at the time of parturition were also seen in case of strongyle egg excretion. Seven (group H) and nine Eimeria spp. (group EF) were found in the calves. The predominant species E. ellipsoidalis, E. zuerni, E. bovis and E. auburnensis were detected for the first time earlier after birth (3-5 weeks) than the others. The prevalence of Eimeria infections increased to 67.1% (group EF) and 50.1% (group H) 9 weeks after birth. Specific IgM and IgA antibody levels (the latter only determined in group EF) in cow sera remained almost constant throughout the observation period, whereas IgG(1) and IgG(2) levels were reduced at the time of parturition. Levels of specific antibodies in sera and colostra were significantly correlated. Except IgM antibodies, significant inverse correlations were found in cows between intensity of infection with E. bovis and specific serum IgG (group H) and IgG(2) (group EF) antibodies. Antibodies to E. bovis were detected in calves sera only after colostrum intake with significant correlations between levels in calves sera and colostra. Levels decreased, starting within the first week of life (most conspicuously in case of IgM and IgA) until the third week. Subsequently, but except IgG(1) antibody concentrations increased until the end of the observation period. Interrelations between antibody levels and the total amount of E. bovis oocysts excreted by the calves until the ninth week of life varied with the age of the animals. Inverse relationships in the first 3 weeks of life as suggested by negative correlation coefficients could not be proven statistically. Thus, there is no unambiguous proof for immunoprotection of calves against E. bovis via maternal immunity. Considering antibody levels in the 3-9 weeks old calves significant direct correlations with E. bovis oocyst excretion were found in case of IgM, IgG(2) and IgA, reflecting an active immune response of young calves to coccidial infection. PMID- 11779652 TI - Transmission dynamics of Cryptosporidium in primates and herbivores at the Barcelona zoo: a long-term study. AB - Factors influencing the transmission of Cryptosporidium in primates and herbivores housed at the Barcelona zoo have been analyzed. The relationship between continuous and discontinuous oocyst shedding, both animal housing conditions and abiotic factors (seasonality, humidity, temperature) was examined to explain the epizootiology of the protozoan. Thirty six fecal samples from each of 11 primates (Pongidae, Cebidae, Cercopithecidae and Lemuridae) and 22 herbivores (Elephantidae, Camelidae, Cervidae, Giraffidae and Bovidae) were examined over the period of 1 year. The parasite transmission was based on the chronic infection status of some animals serving as a source of successive reinfection for other animals. The environmental temperature and humidity (seasonality), the physical features of the facilities, the vicinity of the animals and the physiological status induced by captivity contributed to transmission. The long-term character of this study was essential for obtaining these results and interpreting the complex relationships. PMID- 11779653 TI - Nitric oxide metabolites in naturally occurring canine babesiosis. AB - Babesiosis, caused by the virulent haemoprotozoan parasite Babesia canis rossi, is an important disease of dogs in South Africa. The nitric oxide metabolites, nitrate and nitrite (collectively termed reactive nitrogen intermediates or RNIs) were measured in admission sera from dogs in a babesiosis-endemic area. Five groups were prospectively studied: mild uncomplicated (n=9), severe uncomplicated (severe anaemia) (n=10) and complicated babesiosis (n=11); and two groups of healthy aparasitaemic dogs: endemic controls from the study area (n=10) and experimental dogs kept in tick-free conditions (n=10). Four measures of RNI production were studied: (i) serum RNI; (ii) serum RNI/creatinine ratio; (iii) fractional clearance of RNI (FC(RNI)); (iv) fractional excretion of RNI (FE(RNI)). Marked elevations of serum RNI occurred in only two dogs, both in the severe uncomplicated group. The highest concentration (log value 5.29 micromol/l) was in a dog that died, but concentrations in the other four dogs that died were unremarkable (0, 0.34, 1.66 and 2.64 micromol/l). Age, appetite and free serum haemoglobin were significant covariates for measures of RNI production. There were no significant differences among the babesiosis groups for serum RNI. Adjustment for creatinine had minor effects on the results. All babesiosis groups had significantly higher serum RNI and RNI/creatinine than the tick-free control group, but did not differ from the endemic controls except for the severe uncomplicated group, which had higher RNI/creatinine. The complicated group had significantly lower FC(RNI) and FE(RNI) than all other groups, except for the tick-free control group, which had similar FE(RNI). The results indicate that, in an endemic area, measures of RNI production are unlikely to be useful indicators of severity or outcome in canine babesiosis. PMID- 11779654 TI - Feline heartworm infection: serological survey of asymptomatic cats living in northern Italy. AB - Heartworm infection is now recognized as a potential cause of serious disease in cats. Epidemiological studies indicate that in locations where the infection is endemic in the dog, cats are at risk. The aim of this work was to carry out a serological survey for the presence of anti-Dirofilaria immitis antibodies in privately owned, predominantly asymptomatic cats living in different areas of northern Italy in order to determine the distribution of the parasite and the risk of infection in this species. Serum samples from 1045 cats were evaluated using a commercial antibody (Ab) detection kit (Heska Solo Step Filariosi Felina, Heska Corporation) and results were analyzed together with information obtained by questionnaire. Results showed that 16% of all tested cats were positive for anti-D. immitis antibodies, with values ranging from 9 to 27%, depending on location. Male cats and outdoor cats appeared to be at greater risk, with a significantly higher number of positive antibody tests. The results of this study suggest that the risk of exposure with D. immitis in cats is high in northern Italy and suggest that the use of preventive drugs would be advisable in this area endemic for canine heartworm disease. PMID- 11779655 TI - A simulation model for environmental population densities, survival rates and prevalence of Boophilus decoloratus (Acari: ixodidae) using remotely sensed environmental information. AB - A simulation model for the African tick Boophilus decoloratus is presented. This model is based on the use of a dynamic life table that is driven by abiotic variables (temperature and vegetation status) remotely sensed (AVHRR sensor of the NOAA series of satellites) over time. The model incorporates temperature dependent rates of egg production and development, climate-driven density independent mortality rates, and density-dependent regulation of on-host stages. The model successfully describes both the seasonality and annual variation in the numbers of questing larvae and engorging females observed in eight sites throughout sub-Saharan Africa. Climate data from 1983 to 1999 in 10-day intervals are used as the basic input for modelling the dynamic patterns of activity at four different sites in Africa and to understand how abiotic factors can modulate the long-term life cycle of B. decoloratus. PMID- 11779656 TI - Evaluation of an antibody-ELISA using five crude antigen preparations for the diagnosis of Trypanosoma evansi infection in cattle. AB - Attempts were made to improve the accuracy of an antibody-detection ELISA for the detection of Trypanosoma evansi infection in cattle by improving the method of preparation of the crude antigen used. An IgG-ELISA was performed with five different antigen preparations: crude soluble antigen, soluble and insoluble fractions of crude antigen treated with 0.1% formalin and whole formalin-fixed trypanosomes treated with either trypsin or 2-mercaptoethanol. An IgM-ELISA using crude soluble antigen was also performed. Each ELISA was evaluated using serum from 44 Indonesian cattle infected with T. evansi and 262 uninfected cattle from Australia. There was no significant difference between the sensitivity or specificity of the IgG-ELISA using each of the five antigens. The IgM-ELISA using a crude untreated lysate was significantly less sensitive (p<0.05) than the IgG ELISA using the same antigen, trypsin-treated antigen or the 0.1% formalin treated soluble antigen (68, 64 and 64%, respectively). These results show that these modifications to the method of producing crude antigens for the Ab-ELISA does not improve the accuracy of diagnosis of T. evansi infection in cattle. PMID- 11779657 TI - A study of cystic echinococcosis in slaughter animals in three selected areas of northern Turkana, Kenya. AB - In an attempt to establish the prevalence of cystic echinococcosis, a study was conducted in slaughter animals in three divisions of northern Turkana, Kenya. A total of 5752 goats, 588 sheep, 381 cattle and 70 camels were examined at slaughter. Echinococcus granulosus metacestodes were found in 19.4% of the cattle, 3.6% of sheep, 4.5% of goats and 61.4% of camels. The prevalence of cystic echinococcosis in cattle, sheep and goats was higher in Lokichogio than in either Kakuma or Central divisions. On the other hand, the prevalence of the disease in camels was higher in Central (84.6%) than either Lokichogio (70.6%) or Kakuma (50%). The differences in prevalence rates in different study areas are attributed to differences in environmental conditions, livestock stocking intensity and cross-border migration of livestock. PMID- 11779658 TI - Re: Sodium valproate in cancer-related neuropathic pain. PMID- 11779659 TI - Nebulized glycopyrrolate for drooling in a motor neuron patient. PMID- 11779660 TI - Patient-controlled analgesia with intravenous L-methadone in a child with cancer pain refractory to high-dose morphine. PMID- 11779661 TI - Transmucosal fentanyl in ovarian cancer. PMID- 11779662 TI - A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer related breathlessness. PMID- 11779663 TI - The measurement of symptoms in young children with cancer: the validation of the Memorial Symptom Assessment Scale in children aged 7-12. AB - Few studies have attempted to describe the experience of symptoms in young children with cancer. This is due, in part, to the lack of validated symptom assessment scales for this patient population. The objective of this study was to evaluate the reliability and validity of a revised Memorial Symptom Assessment Scale (MSAS) in patients aged 7-12 as an instrument for the assessment of symptoms in young children with cancer. The MSAS (7-12) was administered to 149 children (inpatients and outpatients) who were undergoing treatment at either the Royal Marsden NHS Trust, London, United Kingdom or The Children's Hospital at Westmead, Sydney, Australia. Validity was evaluated by comparison with the medical record, parental report, and concurrent assessment on visual analogue scales for selected symptoms. The data provide evidence of the reliability and validity of MSAS (7-12) and demonstrate that children with cancer as young as 7 years can report clinically relevant and consistent information about their symptom experience. Young children with cancer experience multiple symptoms. Approximately one-third had experienced lethargy and/or pain and/or insomnia during the 48 hours prior to the completion of MSAS (7-12). The completion rate for MSAS (7-12) was high and the majority of children completed the instrument in a short period of time and with little difficulty. The instrument appears to be age appropriate and may be helpful to older children unable to independently complete MSAS (10-18). Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in cancer chemotherapy drug trials. PMID- 11779664 TI - Profile and evaluation of a palliative medicine consultation service within a tertiary teaching hospital in Sydney, Australia. AB - The role of a Palliative Medicine Liaison Consultation Service (LCS) in a large tertiary referral teaching hospital was examined by the prospective evaluation of 50 cases consecutively referred, together with the subsequent advice/recommendations (4 categories: pharmacological, non-pharmacological, clarification of goal of treatment, care system upon discharge) given during the consultation. The utility of a simple scoring system in quantifying the impact (4 grades: deleterious, no effect, positive, very positive) of the advice given on individual patient outcome, scored by both the referring team and the LCS, was studied. Eighty percent of cases had a cancer diagnosis. Pain was the most common symptom (50% cases) and "pain control" the most common referral reason cited. The median number of recommendations per patient was 3.0 and the majority (70%) concerned symptom control recommendations. Advice was given regarding discharge planning in nearly two-thirds of cases and such advice dealing with the care system upon discharge was judged by the referring team to have the highest positive impact of all recommendations. Nearly three-fourths of cases (74%) were graded by the referring team as having at least one recommendation with a positive impact. The simple scoring system used is demonstrably a useful outcome assessment tool. The LCS is perceived to have a positive impact on patient care in an acute hospital setting and appears to fill a gap in the multi-specialty provision of care. PMID- 11779665 TI - Second single 4 Gy reirradiation for painful bone metastasis. AB - To investigate the efficacy of the second 4 Gy given as a single fraction radiotherapy (RT) for patients with painful bone metastasis who had already twice received single fraction RT (4, 6, or 8 Gy plus 4 Gy), a total of 25 patients were assessed before and after re-irradiation. The patients included 19 responders and 6 nonresponders to two prior single fraction RT, the latter one being 4 Gy. The overall response rate was 80%, with both complete response (CR) and partial response (PR) being 40%. No difference was found between the previous responders and previous nonresponders regarding both CR (P = 0.70) and overall response rate (P = 0.35). Response duration was longer in the previous responders (P = 0.0041), but the time to pain relief was similar between the two treatment groups. No acute or late high-grade toxicity was observed during this study and no pathological fractures or spinal cord compressions were seen. In this small and highly selected series of patients, the third single fraction RT of 4 Gy was effective and not toxic in the treatment of painful bone metastasis. PMID- 11779666 TI - Factors associated with the accuracy of family caregiver estimates of patient pain. AB - This study identified factors associated with inaccurate family caregiver assessments of patient pain. Participants were 31 caregiver-patient dyads receiving hospice home care. All patients had a primary diagnosis of end-stage cancer. As expected, caregivers overestimated patient pain. The degree of disparity for each dyad was calculated by subtracting the patient's pain rating from the caregiver's rating of patient pain. Caregiver knowledge of cancer pain management was not related to the degree of disparity in pain ratings, but caregivers' experience of patient pain was significantly related to accuracy of caregivers' pain ratings. Those caregivers who 1) perceived their loved one to be in a great deal of distress secondary to pain, 2) associated greater efforts at pain relief (i.e., more medication) with greater levels of pain, and 3) were themselves distressed by the patient's pain had the most inaccurate estimates of patient pain. There was a trend for greater disparity in pain estimates to be related to poorer existential quality of life for patients. Overall, the findings suggest that health care providers need to take into consideration family members' interpretation of patient pain when providing pain management education services. PMID- 11779667 TI - A Quebec survey of issues in cancer pain management. AB - We report the results of a cancer pain survey mailed to Quebec hematologist oncologists and palliative care physicians in 1999. The survey was designed to sample views on the current status of pain management and on obstacles to the provision of adequate pain relief for patients. The survey, formulated by an ethics network centered at the Clinical Research Institute of Montreal, was distributed to all members of the Association of Hematologist-Oncologists of Quebec and to all physician members of the Quebec Palliative Care Association. Responses were obtained from 138 Palliative Care Association members (response rate 61%) and 76 hematologist-oncologists (response rate 45%). Major obstacles reported included inadequate assessment of both contributory psychosocial issues and severity of pain, patient reluctance to take opioids, and inadequate access to non-drug techniques for pain relief. Access to opioids was not regarded as a problem. Both groups felt generally competent in their ability to manage various aspects of cancer pain therapy. They gave little credit to their formal medical school or residency training. Fifty-six percent of the palliative care group and 57% of the hemato-oncologists rated their medical school experience as only "poor" or "fair" on a 4-point scale. Residency ratings were modestly better. We conclude that medical faculties should assign a high priority to teaching health professionals patient assessment techniques. Simple symptom assessment scales should be routinely used in oncology/palliative care practice. Medical school training in pain management is not highly regarded and should be enhanced. We also note that, based on response to the scenario of a patient presenting with severe pain, many physicians, while feeling competent in the use of opioids, may be overly conservative in their initial use. PMID- 11779668 TI - Low-dose oral naloxone reverses opioid-induced constipation and analgesia. AB - The most common side effect of opioid therapy is constipation. It is often difficult to treat and is believed to be primarily a peripheral effect. Single large doses of oral naloxone have been shown to be efficacious in reversing opioid-induced constipation. However, they often cause the unwanted side effect of analgesia reversal. This study evaluated the effects on constipation and analgesia of low doses of oral naloxone given three times daily. Patients taking stable doses of opioids with complaints of constipation were recruited for this double-blind, randomized, placebo-controlled study. Patients were given 4 mg or 2 mg of oral naloxone, or placebo, three times daily. Stool frequency and symptoms related to constipation were recorded daily. Patients also recorded the daily amount of analgesics required to maintain pain control. Nine patients were recruited for the study. All the patients who received oral naloxone had some improvement in their bowel frequency. Three of the patients also experienced reversal of analgesia, including one who had complete reversal of analgesia. This study demonstrates that reversal of analgesia still occurred despite dividing the oral naloxone into very low doses relative to the total dose of opioid used. Patients using high doses of opioids appear to be the most vulnerable to the analgesic effect of oral naloxone. PMID- 11779669 TI - Vowing to care. PMID- 11779670 TI - Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients. AB - To evaluate the role of oral ketamine as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain, 9 cancer patients (5 men, 4 women) taking maximally tolerated doses of either morphine, amitriptyline, sodium valproate, or a combination of these drugs for intractable neuropathic pain, and reporting a pain score of >6 on a 0-10 scale, were studied prospectively to evaluate analgesia and adverse effects. Ketamine in the dose of 0.5 mg/kg body weight three times daily was added to the existing drug regimen. Patients were taught to maintain a pain diary wherein they daily recorded their pain, sedation, and vomiting scores, and other side effects. A decrease of more than 3 from the baseline in the average pain score, or a score of < or =3 was taken as a successful response. Seven patients exhibited a decrease of more than 3. Four patients experienced nausea, of which one had vomiting. Two developed loss of appetite. Eight patients reported drowsiness during the first two weeks of therapy (P = 0.001), and this gradually improved over the next two weeks in 5 of these 8 patients. Three patients withdrew from the study, two owing to excessive sedation and another due to a "feeling of unreality." None of the patients reported visual or auditory hallucinations. This experience suggests that low dose oral ketamine is beneficial and effective in the management of intractable neuropathic pain in patients with advanced cancer. However, its utility is limited in some patients by the adverse effects that accompany its use. PMID- 11779671 TI - Myoclonus secondary to withdrawal from transdermal fentanyl: case report and literature review. AB - Myoclonus is a common and well-described adverse effect of opioids. Most cases reported in the literature have been associated with opioid administration, rather than with opioid withdrawal. We describe a case of myoclonus secondary to withdrawal from transdermal fentanyl. We review the literature regarding myoclonus related to opioid therapy (opioid-induced myoclonus) and withdrawal (opioid withdrawal myoclonus), and discuss possible mechanisms and therapies for these phenomena. PMID- 11779672 TI - Nebulized furosemide as a novel treatment for dyspnea in terminal cancer patients. AB - Three terminal cancer patients with severe dyspnea were treated with nebulized furosemide. The underlying causes of dyspnea varied. Twenty milligrams of furosemide was nebulized and inhaled four times each day. Dyspnea dramatically improved and could be controlled for weeks. No noticeable side effects were observed. Inhalation of nebulized furosemide seems to be an effective and useful treatment for dyspnea in terminal cancer patients, but these observations need to be confirmed in a randomized controlled trial. PMID- 11779681 TI - Artificial-intelligence-augmented systems. PMID- 11779682 TI - Predicting glaucomatous visual field deterioration through short multivariate time series modelling. AB - In bio-medical domains there are many applications involving the modelling of multivariate time series (MTS) data. One area that has been largely overlooked so far is the particular type of time series where the dataset consists of a large number of variables but with a small number of observations. In this paper, we describe the development of a novel computational method based on genetic algorithms that bypasses the size restrictions of traditional statistical MTS methods, makes no distribution assumptions, and also locates the order and associated parameters as a whole step. We apply this method to the prediction and modelling of glaucomatous visual field deterioration. PMID- 11779683 TI - Lung cancer cell identification based on artificial neural network ensembles. AB - An artificial neural network ensemble is a learning paradigm where several artificial neural networks are jointly used to solve a problem. In this paper, an automatic pathological diagnosis procedure named Neural Ensemble-based Detection (NED) is proposed, which utilizes an artificial neural network ensemble to identify lung cancer cells in the images of the specimens of needle biopsies obtained from the bodies of the subjects to be diagnosed. The ensemble is built on a two-level ensemble architecture. The first-level ensemble is used to judge whether a cell is normal with high confidence where each individual network has only two outputs respectively normal cell or cancer cell. The predictions of those individual networks are combined by a novel method presented in this paper, i.e. full voting which judges a cell to be normal only when all the individual networks judge it is normal. The second-level ensemble is used to deal with the cells that are judged as cancer cells by the first-level ensemble, where each individual network has five outputs respectively adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, and normal, among which the former four are different types of lung cancer cells. The predictions of those individual networks are combined by a prevailing method, i.e. plurality voting. Through adopting those techniques, NED achieves not only a high rate of overall identification, but also a low rate of false negative identification, i.e. a low rate of judging cancer cells to be normal ones, which is important in saving lives due to reducing missing diagnoses of cancer patients. PMID- 11779684 TI - Artificial neural network assessment of substitutive pharmacological treatments in hospitalised intravenous drug users. AB - Artificial neural networks (ANNs) provide better solutions than linear discriminant analysis (LDA) to problems of classification and estimation involving a large number of non-homogeneous (categorical and metric) variables. In this study, we compared the ability of traditional LDA and a feed-forward back propagation (FF-BP) ANN with self-momentum to predict pharmacological treatments received by intravenous drug users (IDUs) hospitalised for coexisting medical illness. When medical staff considered detoxification appropriate they usually suggested methadone (MET) and (or) benzodiazepines (BDZ). Given four different treatment options (MET, BDZ, MET+BDZ, no treatment) as dependent variables and 38 independent variables, the FF-BP ANN provided the best prediction of the consultant's decision (overall accuracy: 62.7%). It achieved the highest level of predictive accuracy for the BDZ option (90.5%), the lowest for no treatment (29.6), often misclassifying no treatment as BDZ. The LDA yielded a lower mean accuracy (50.3%). When the untreated group was excluded, ANN improved its absolute recognition rate by only 1.2% and the BDZ group remained the best predicted. In contrast, LDA improved its absolute recognition rate from 50.3 to 58.9%, maximum 65.7% for the BDZ group. In conclusion, the FF-BP ANN was more accurate than the statistical model (discriminant analysis) in predicting the pharmacological treatment of IDUs. PMID- 11779685 TI - The problem of bias in training data in regression problems in medical decision support. AB - This paper describes a bias problem encountered in a machine learning approach to outcome prediction in anticoagulant drug therapy. The outcome to be predicted is a measure of the clotting time for the patient; this measure is continuous and so the prediction task is a regression problem. Artificial neural networks (ANNs) are a powerful mechanism for learning to predict such outcomes from training data. However, experiments have shown that an ANN is biased towards values more commonly occurring in the training data and is thus, less likely to be correct in predicting extreme values. This issue of bias in training data in regression problems is similar to the associated problem with minority classes in classification. However, this bias issue in classification is well documented and is an on-going area of research. In this paper, we consider stratified sampling and boosting as solutions to this bias problem and evaluate them on this outcome prediction problem and on two other datasets. Both approaches produce some improvements with boosting showing the most promise. PMID- 11779686 TI - Empirical evaluation of a hybrid intelligent monitoring system using different measures of effectiveness. AB - The validation of a software product is a fundamental part of its development, and focuses on an analysis of whether the software correctly resolves the problems it was designed to tackle. Traditional approaches to validation are based on a comparison of results with what is called a gold standard. Nevertheless, in certain domains, it is not always easy or even possible to establish such a standard. This is the case of intelligent systems that endeavour to simulate or emulate a model of expert behaviour. This article describes the validation of the intelligent system computer-aided foetal evaluator (CAFE), developed for intelligent monitoring of the antenatal condition based on data from the non-stress test (NST), and how this validation was accomplished through a methodology designed to resolve the problem of the validation of intelligent systems. System performance was compared to that of three obstetricians using 3450 min of cardiotocographic (CTG) records corresponding to 53 different patients. From these records different parameters were extracted and interpreted, and thus, the validation was carried out on a parameter-by-parameter basis using measurement techniques such as percentage agreement, the Kappa statistic or cluster analysis. Results showed that the system's agreement with the experts is, in general, similar to agreement between the experts themselves which, in turn, permits our system to be considered at least as skillful as our experts. Throughout our article, the results obtained are commented on with a view to demonstrating how the utilisation of different measures of the level of agreement existing between system and experts can assist not only in assessing the aptness of a system, but also in highlighting its weaknesses. This kind of assessment means that the system can be fine-tuned repeatedly to the point where the expected results are obtained. PMID- 11779688 TI - Splice variants of human beta 1 integrins: origin, biosynthesis and functions. AB - The integrin beta1 subfamily of adhesion receptors consists of 12 members and forms the biggest subfamily among integrins. Human integrin subunit beta1 has five cytoplasmic splice variants (beta1A, beta1B, beta1C-1, beta1-C2, beta1D). Even though cytoplasmic splice variants do not change the ligand-specificity of a beta1 integrin, clustering of these different splice variants triggers signaling pathways that lead to a different cellular response. The main focus of this review is on the origin and specific functions of the less abundant human integrin beta1 splice variants (B, C-1, C-2, D). PMID- 11779689 TI - Anti-idiotypic DNA vaccines for B-cell lymphoma therapy. AB - The idiotypic determinants expressed by immunoglobulin at the surface of malignant B-cells provide specific targets for vaccination strategies. However, as self-antigens they are poorly immunogenic and vaccines must include carriers to improve immune responses. Chemical cross-linking of purified idiotypic protein is so far the only method which has been employed in clinical trials while a number of second-generation vaccines have been developed in mouse models. These strategies are based on the use of recombinant DNA technology to create fusion proteins that contain the idiotype genetically linked to molecules that act as immunological adjuvants. Fusion proteins can be made available to the immune system by direct delivery of naked DNA with great advantages in terms of time and costs. The most relevant approaches are listed and discussed with particular emphasis to the mechanism by which different molecules exert their adjuvant effect. The role of cellular versus antibody mediated suppression of tumor growth following Id vaccination is examined by comparing the most recent data on the mechanism of tumor protection. In addition, an analysis of the specificity of anti-idiotypic antibodies induced by scFv-DNA vaccination as compared to protein immunization is provided. PMID- 11779690 TI - Regulation of Vav proteins by intramolecular events. AB - The Vav family is a group of signal transduction molecules with oncogenic potential that play important roles in development and cell signaling. The function of Vav proteins co-evolved with tyrosine kinase pathways, probably to assure the optimal conversion of extracellular signals into intracellular responses coupled to the cytoskeleton and the transcriptome. To date, the best known function of Vav proteins is their role as GDP/GTP exchange factors for Rho/Rac molecules. This activity is highly regulated during signal transduction by processes involving intramolecular interactions among several domains of Vav proteins. On one hand, the phosphorylation of Vav proteins on a specific tyrosine residue leads to a conformational change that allows the activation of the catalytic activity of Vav proteins. This mechanism of activation has been recently explained in structural terms and shown to involve the acidic and Dbl homology domains of Vav. On the other hand, the activity of Vav proteins is affected by a second type of intramolecular interaction occurring between the plekstrin-homology and the catalytic regions of Vav that is regulated by phospholipids. In this review, we will give a brief overview of the recent advances in this field. PMID- 11779691 TI - The effects of phosphorylation on adaptor protein function. AB - Adaptor proteins are specialized protein binding partners that serve to link signaling proteins to each other, as a mechanism to propagate a cellular signal. Ultimately, these signals are required for a specific biological response. Thus, it is important that the cell develop mechanisms to regulate these signaling cascades. One way these cascades can be regulated is through post translational modifications of adaptor proteins which would regulate their ability to forge protein-protein interactions. In this review, we summarize the effects of serine/threonine and tyrosine phosphorylation on adaptor protein function, with a specific focus upon those adaptor proteins in which phosphorylation has been demonstrated to regulate a signaling cascade or biological response. PMID- 11779693 TI - Function and dysfunction of the human oncoprotein MDM2. AB - The protein MDM2 coded by the human homologue of mouse double minute-2 (mdm2) gene frequently overexpresses in malignant human breast and other tumors. Artificial amplification of mouse mdm2 gene derived from a transformed murine cell line enhances tumorigenic potential of murine cells. These evidences suggest oncogenic properties of human or mouse MDM2. The tumorigenic property of MDM2 is not unexpected as MDM2 can inactivate several functions of the tumor suppressor p53. The protein also interacts with several cell cycle regulatory proteins that may contribute to its tumorigenic ability. Several spliced forms of MDM2 have been detected in cells that overexpress MDM2. The function of the proteins coded by these spliced forms is not well understood. Overexpression of full-length MDM2 from its cDNA arrests G1 to S phase transition of normal human or murine cells. Elimination of the growth inhibitory domains of the oncoprotein induces tumorigenesis. Some cancer-derived cell lines are partially insensitive to MDM2 mediated growth arrest. Normal cells can induce MDM2 in response to oncogenic challenges such as UV irradiation or estrogen treatment. Normal cells may induce full-length MDM2 in response to oncogenic challenges to protect against premature cell cycle progression. If the oncoprotein is defective in growth arrest or if the cells are insensitive to MDM2 mediated growth arrest, premature progression of cell cycle may lead to tumorigenesis. Elucidation of the growth regulatory functions of MDM2 may help develop new drug design for cancer treatment. PMID- 11779692 TI - Control of calcium entry in human fibroblasts by frequency-dependent electrical stimulation. AB - Modulation of intracellular calcium ion concentration ((Ca2+)i) could be used to control cellular and molecular responses that are important in cell and tissue engineering. Electrical stimulation (ES) has been used to activate plasma membrane ion channels including Ca2+channels, and to induce changes in (Ca2+)i. Strong direct current (dc) ES depolarizes the membrane electrical potential (MEP) and, thereby, causes rapid increases in (Ca2+)i. Electrocoupling mechanisms that could control (Ca2+)i increases induced by modes of ES other than dc have not been elucidated, however. Here we report that 30 min of continuous exposure to a 1 or 10 Hz, 2 V/cm ES induces an (Ca2+)i increase by approximately 6-fold (baseline 25 nM) in human fibroblasts in culture. In contrast, a 100 Hz, 2 V/cm ES causes no significant (Ca2+)i increase. Either depletion of Ca2+from the extracellular medium or incubation of cells with verapamil inhibits the (Ca2+)i increase, indicating that Ca2+ influx through verapamil-sensitive Ca2+channels is required for the (Ca2+)i increase induced by oscillatory ES. More intense ES by a 1 Hz or a dc 10 V/cm electric field causes a rapid 20 to 25-fold (Ca2+)i increase. We hypothesize that selective, partial activation of Ca2+channels is likely to mediate Ca2+influx. These results suggest that optimal ES could be used to control Ca2+entry and, thereby, regulate cellular calcium homeostasis without adversely affecting cell viability. PMID- 11779694 TI - Experimental acute pancreatitis: new insights into the pathophysiology. AB - Acute pancreatitis is a disease of variable severity in which patients can experience mild or severe attacks. Most observers believe that acute pancreatitis results from an early intra-acinar cell activation of inactive zymogens into their active forms. Following this early activation, a trypsin cascade occurs in the gland which leads to the auto-digestion of acinar cells. Recent experimental data indicate that synthesis and release of pro-inflammatory cytokines and chemokines are also responsible for local injury and systemic dispersion of the inflammatory mediators. Experimental studies also provide evidence for the involvement of the immune system in the development of pancreatitis, including lymphocyte and neutrophil activation. However, the factors that will dictate the ultimate severity of the attack are still unknown. Following an attack, the pancreas completely recovers or becomes fibrotic through the action of newly described mediators within the pancreas such as TGF-beta and IGF-1 and the presence of pancreatic stellate cell that is known to play a crucial role in the fibrogenesis. PMID- 11779696 TI - Tumor markers for the early detection of bladder cancer. AB - Several urine markers have been and are currently being investigated for the diagnosis and prognostication of bladder malignancies. While cystoscopy and urine cytology remain the gold standard in the detection of bladder cancer, cystoscopy is invasive and cytology yields low sensitivities in low-grade disease. The availability of a non-invasive, accurate, office-based test would be ideal. In this review, we discuss markers that are useful in the prevention and detection of transitional cell carcinoma of the bladder. In general, each of the markers has better sensitivities than cytology, but lower specificities. Furthermore, each of these markers must still be used in adjunct with cystoscopy. PMID- 11779695 TI - Autoinhibition of Sos by intramolecular interactions. AB - Sos proteins function as activators of Ras signaling by catalyzing guanine nucleotide exchange on Ras. Sos regulation was initially thought to be accomplished primarily through its growth factor-dependent recruitment to the plasma membrane. More recent data has indicated that while membrane association is an indispensable means of Sos regulation, additional mechanisms involving intramolecular interactions function to control Sos activity towards Ras. This review will examine the experimental evidence for Sos intramolecular interactions and their contribution to Sos regulation. PMID- 11779697 TI - Cellular signaling pathways engaged by the Epstein-Barr virus transforming protein LMP1. AB - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is an essential component of the viral machinery that orchestrates cellular transformation and oncogenesis. The critical role of LMP1 in transformation has been established through recombinant genetic analysis of the EBV genome, ectopic expression in cell lines and transgenic mice and immunohistochemical analysis of EBV- associated tumor specimens. The principal mechanism of LMP1 function is based on mimicry of activated cell surface receptors of the tumor necrosis factor superfamily. LMP1 signaling culminates in the activation of transcription factors NF-kappaB, AP1 and STAT1/3, which have been tightly linked to prevention of apoptosis and malignant transformation. The molecular mechanisms of LMP1 function will be reviewed in this report. PMID- 11779698 TI - The role of sodium channels in cell adhesion. AB - Voltage-gated sodium channels are unique in that they combine action potential conduction with cell adhesion. Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. The alpha subunits are members of a large gene family containing the voltage-gated sodium, potassium, and calcium channels. Sodium channel alpha subunits form a gene subfamily with at least eleven members. Mutations in sodium channel alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome (LQT), and hyperkalemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode the sodium channel beta subunits with at least one alternative splice product. Unlike the pore-forming alpha subunits, the sodium channel beta subunits are not structurally related to beta subunits of calcium and potassium channels. Sodium channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. We have shown that beta subunits also function as cell adhesion molecules (CAMs) in terms of interaction with extracellular matrix molecules, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. A mutation in SCN1B has been shown to cause GEFS+1 epilepsy in human families. We propose that the sodium channel signaling complex at nodes of Ranvier involves beta subunits as channel modulators as well as CAMs, other CAMs such as neurofascin and contactin, RPTPbeta, and extracellular matrix molecules such as tenascin. Finally, we explore other subunits of voltage-gated ion channels as potential CAM candidates. PMID- 11779699 TI - Manipulation of the cell cycle by human cytomegalovirus. AB - The human cytomegalovirus-induced changes to the transcriptome and proteome of infected cells in many ways resemble an abortive mitogenic response. The virus induces quiescent cells to re-enter the cell cycle, but they are prevented from entering the S phase, where the synthesis of the cellular genome would compete with that of the virus for the available precursors for DNA replication. The mechanisms of these cell cycle alterations include transcriptional induction and repression, post-translational modifications and changes in protein stability. Essentially every class of cell cycle regulators is affected, and some of the key proteins are targeted by multiple different mechanisms. While the effects on cell cycle progression of viral infection, and of individual viral genes outside the context of viral infection have been described, it is now important to synthesize these two experimental approaches to gain a more complete understanding of how and why human cytomegalovirus infection affects cell cycle progression. PMID- 11779700 TI - Perspectives in studies of human tumor viruses. AB - Tumor viruses can be found in both the RNA and DNA virus kingdoms. All RNA tumor viruses belong to the retrovirus family. Directly transforming Class I RNA tumor viruses carry cellular oncogenes, picked up by accidental recombination, and usually selected for secondary modifications and high tumorigenicity by the investigator. They are not known to play any role for tumor causation in nature. Class II or chronic RNA tumor viruses do not carry cell-derived oncogenes but they often act by proviral DNA insertion into the immediate neighborhood of a cellular oncogene. Feline, murine, and avian leukemia viruses belong to this category. The human adult T-cell leukemia virus, (HTLV-1) and bovine leukemia virus (BLV) act by expanding the preneoplastic cell population and thereby provides the soil for secondary, cellular changes. The DNA tumor viruses belong to three very different categories, the papovaviruses, adenoviruses and herpesviruses. Inactivation of the Rb and the p53 pathway by the viral transforming proteins is a convergent feature of the papova- and the adenoviruses. Since all DNA tumor viruses kill their host cell following their entry into the lytic phase, transformation and tumorigenicity are entirely dependent on a non-lytic interaction. Cells transformed by DNA tumor viruses depend on the continued expression of the virally encoded oncogene. They provide thereby a convenient target for the immune surveillance of the host. Depending on the epidemiological history of the virus in relation to its natural host species, the immune surveillance of the host and the strategy of viral latency and survival can evolve into a truly symbiotic relationship, as best illustrated by the Epstein-Barr virus (EBV). Tumor development occurs only as an accident at the level of the host (immunosuppression) or the cell (specific translocations or other genetic changes). The list of human viruses presently known to cause or to contribute to tumor development comprise four DNA viruses, namely Epstein-Barr virus, certain human papilloma viruses subtypes, hepatitis B virus, and Kaposi sarcoma herpesvirus (HHV-8); and two RNA viruses, adult T-cell leukemia virus (HTLV-1) and hepatitis virus C. PMID- 11779701 TI - Near real-time in vivo confocal imaging of mouse mammary tumors. AB - The goal of this study was to evaluate the ability of near real-time reflectance confocal microscopy to image tumor metastasis in vivo in an animal model. We used an epi-illumination confocal microscope to capture images of mouse mammary tumors in nude immunodeficient and Balb/C immunocompetent mice. In vivo confocal images and videos of normal and neoplastic areas were obtained before and after the application of a 6% acetic acid solution, with a lateral resolution of 0.8 microns and an axial resolution of 2-3 microns. Average imaging depths ranged from 150 microns to greater than 300 microns. We were able to differentiate between normal and abnormal tissue areas within the mammary gland, including areas of adipose tissue, fibroblasts and connective tissue, neoplastic tissue, and blood flow within blood vessels. Intravital imaging with reflectance confocal microscopy appears to be a useful tool to study tumor metastasis in vivo. PMID- 11779702 TI - The role of plasma membrane Ca2+ pumps (PMCAs) in pathologies of mammalian cells. AB - The biochemical function of the plasma membrane calcium ATPases (PMCAs) is the extrusion of cytosolic Ca2+ from the cell. Although this general function is well documented, the role of the complex isoform diversity and especially the contribution of specific isoforms to pathological conditions is less well understood. No human disease has been linked to a defect in any of the four PMCA genes. Nevertheless, isoforms do not have redundant functions, as shown by the indispensable role of PMCA2 demonstrated in transgenic mice. This review summarizes the results of recent analysis of the PMCA dysregulation in diseased cells or model systems of pathological conditions, including both acute disorders like hypoxia/ischemia and seizure, and slowly progressing dysfunctions like Alzheimer's disease, hypertension, diabetes and aging. Abnormalities in PMCA or its regulators have been described in various organs, reflected in changes of expression levels or in modifications or proteolysis of the PMCA protein. Changes of PMCA function are often detected in cell types different from the specific type involved in the pathology, pointing to more general defects. Examples are erythrocytes in diabetes and blood platelets in hypertension. The changes suggest the significance of PMCA in Ca2+ homeostasis both in excitable and non-excitable cells. PMID- 11779703 TI - Plasminogen activation on the cell surface. AB - The plasminogen activation system appears to be widely involved in many biological processes in health and disease, but the regulation of plasmin generation or the mechanisms of stimulation by cell surface receptors are not well understood. Cell surface plasminogen activation requires binding sites for plasminogen substrate and activator enzyme before enhancement of plasmin generation rate is observed. The cell surface moieties involved in binding these reactants appear to be a mixed group of proteins and other molecules, many of which have been extensively investigated. The binding of plasminogen in particular is characterized by heterogeneous receptor molecules, present in high number but generally with low affinity for plasminogen. The low affinity of the interaction, with Kd values around 10(-6) M, presents considerable technical difficulties when studying and quantitating plasminogen binding to cells or isolated receptors. Studying plasminogen activation kinetics in the presence of cells also presents technical difficulties and raises difficult questions on interpretation of results. However, approaches developed to study enzyme activation systems in other areas of hemostasis may also be applied to the problems associated with pericellular proteolysis. Models should be developed that match In vitro experimental data and help us understand the meaning of kinetic constants derived from these systems. In this way it should be possible to better understand the regulation of plasminogen activation around the cell under normal conditions and in a variety of disease states where cell-associated plasminogen activation is believed to be up-regulated. Ultimately, a sound understanding of theses regulatory mechanisms will enable us to devise strategies for modulating proteolytic activity, test these approaches in well designed In vitro systems and relate these results to the in vivo situation. PMID- 11779704 TI - Immunotherapy of cancer using heat shock proteins. AB - Tumor derived heat shock protein (hsp)-peptide complexes (particularly hsp70 and grp94/gp96) have been demonstrated to serve as effective vaccines, producing anti tumor immune responses in animals and in man. This approach utilizes the peptide binding properties of stress proteins which are responsible for their functions as molecular chaperones in numerous cellular processes. The present review briefly introduces the reader to the basic stress protein families, i.e. heat shock and glucose regulated proteins, their regulation, compartmentalization and family members. It then introduces the reader to aspects of hsps/grp function and interactions with the host's immune system. An overview of the conventional uses of hsp/grp vaccines as autologous vaccines derived from cancers is presented. We then discuss other stress protein related vaccination approaches. This includes the use of recombinant antigens, both proteins and peptides, naturally complexed to hsp/grps; hsp/grp DNA vaccines, hsp/grp fusion proteins and cell based hsp/grp vaccines. The advantages and disadvantages of each vaccination approach are discussed. Lastly, means of further enhancing the already potent activity of stress protein vaccines are presented, specifically the use of hyperthermia or CTLA-4 blockade as adjuvants. PMID- 11779705 TI - Angiogenic factors and bladder cancer. AB - Angiogenesis is required for the growth as well as expansion of a solid tumor. It has been reported that tumor angiogenesis may be triggered after an increase in the level of angiogenic factors and a concomitant decrease in the level of angiogenic inhibitors. Of all potential pro-angiogenic mediators of bladder cancer, VEGF and bFGF appear to be most relevant in terms of physiology. To date, it appears that the angiogenic factors and inhibitors may play an important role in the diagnosis and prognosis of bladder cancer. PMID- 11779706 TI - Protein tyrosine phosphatases. AB - The molecular mechanisms of signal transduction have been at the focus of increasingly intense scientific research. As a result, our understanding of protein tyrosine kinase-mediated signaling has advanced at an unprecedented pace during the past decade. In contrast, the study of protein tyrosine phosphatases has lagged behind, but is now gathering momentum and is predicted to become a "hot topic" in the field within the next few years. This review summarizes the current state-of-the art in our understanding of the structure, regulation and role of protein tyrosine phosphatases with emphasis on the lymphocyte system. PMID- 11779707 TI - Cell cycle dysregulation by HTLV-I: role of the tax oncoprotein. AB - HTLV-I is a human retrovirus which is the etiological agent for adult T-cell leukemia. The virus encodes a 40 kDa oncoprotein, Tax, which has no cellular counterpart. Findings from several laboratories over the past decade have shown that over-expression of the Tax oncoprotein is wholly sufficient to transform animal cells. Emerging evidence supports that Tax transforms cells through dysregulation of several cell cycle checkpoints. Here, we review extant data on how Tax targets cyclins, inhibitors of cyclin dependent kinase, as well as cellular sentries for DNA-damage. PMID- 11779708 TI - Retinoids in liver fibrosis and cancer. AB - Pathobiological functions and metabolism of retinoids (vitamin A and its derivatives) in liver fibrosis and hepatocellular carcinoma (HCC) are discussed in the present review. Retinoic acid (RA, active metabolite) exacerbates liver fibrosis that is not accompanied by hepatic necroinflammation, in which RA acts directly on hepatic stellate cells (HSCs); RA enhances plasminogen activator/plasmin levels and thereby induces proteolytic activation of latent transforming growth factor-beta (TGF-beta), a strong fibrogenic cytokine, resulting in enhanced collagen production. We have developed a protease inhibitor, camostat mesilate, that suppresses TGF-beta activation and thereby inhibits the transformation of HSCs, leading to reduced matrix production by the cells. The compound is effective not only in preventing but also in reducing hepatic fibrosis in rats when administered orally. HCC is refractory to RA due to its local depletion in the tumors and also due to malfunction of its nuclear receptor, retinoid X receptor-alpha (RXRalpha) Oral supplementation of a synthetic retinoid named acyclic retinoid led to the disappearance of serum lectin-reactive alpha-fetoprotein (AFP-L3) and subsequently suppressed posttherapeutic recurrence of HCC in cirrhotic patients. These results suggest eradication of AFP-L3-producing latent malignant clones from the liver by the retinoid. We propose the concept of "clonal deletion" therapy for cancer chemoprevention, a new category of cancer chemotherapy. PMID- 11779709 TI - Tyrosine phosphorylation of paxillin, FAK, and p130CAS: effects on cell spreading and migration. AB - Integrins are transmembrane receptors that mediate cell attachment to the substrate. At the cytoplasmic surface of the integrin, cytoskeletal proteins cluster into focal adhesions. The focal adhesions contain multiple proteins that provide a structural and signaling complex inside the cell. This review focuses on three of the cytoskeletal components of the focal adhesion, paxillin, FAK, and p130CAS, that are phosphorylated and play a regulatory role in cell spreading and cell migration. A brief discussion is included of tyrosine phosphorylation of the integrin in relation to localization and phosphorylation of these cytoskeletal proteins. The phosphorylation of integrins and cytoskeletal proteins regulates localization and downstream signaling with profound effects on cell movement. PMID- 11779710 TI - Coupling kinase activation to substrate recognition in SRC-family tyrosine kinases. AB - Signal transduction molecules translate extracellular inputs into their corresponding intracellular responses. Given the complexity and number of signaling pathways present in the eukaryotic cell, it is not surprising that the functions of signaling molecules are often tightly regulated. Autoinhibition is a prevalent mechanism for governing the function of signaling molecules. The relationship between the viral, oncogenic form of Src (v-Src) and the corresponding cellular proto-oncogene (c-Src) highlights the importance of inhibitory intramolecular interactions. Src provides an example of the dramatic cellular consequences arising from the loss of autoregulation. PMID- 11779711 TI - 3D-computer based reconstructions of apoptotic nuclei. AB - We present a 3D-model of apoptotic nuclei of HL-60 cells treated with 10 g/ml Etoposide (topoisomerase II inhibitor) for 24 hours. The static model was generated from a series of optical sections obtained through a confocal microscope by freeware and shareware graphical programs available in the Internet. Its animation was done by 3D Studio Max. We demonstrate the appearance of typical fragmentation and condensation of chromatin accompanied by its aggregation to the inner side of the nuclear membrane. PMID- 11779712 TI - Targeting actin remodeling profiles for the detection and management of urothelial cancers--a perspective for bladder cancer research. AB - The actin cytoskeleton and numerous proteins associated with its regulation and function constitute over 25% of total proteins in the cell. Growing evidence from this laboratory and others shows that alterations of actin polymerization, or actin remodeling, plays a pivotal role in regulating the morphologic and phenotypic events of a malignant cell. The actin remodeling is the result of activation of oncogenic actin signaling pathways (e.g., Ras and Src), or inactivation of several important actin-binding proteins that have tumor suppressive functions (e.g., Gelsolin, E-Cadherin, etc.). Recently distinctive protein expression patterns of some of these genes in bladder cancer carcinogenic and progressive processes have been observed. Specific actin-pathway antagonists that have growth inhibitory effect on transformed cells, but not normal cells, have been developed. Our overall hypothesis is that actin alterations are progressive and that distinctive actin remodeling profiles are associated with different stages of cancer development and progression. These patterns can be used as markers for cancer early detection and prognostic indication. On the other hand, detection of specific types of actin-signaling pathway alterations also enables a targeted preventive or therapeutic intervention with specific actin signaling pathway blockers, thereby providing an actin-based paradigm for individualized monitoring and intervention of human bladder cancer. PMID- 11779713 TI - Entry into host cells by Legionella. AB - Many respiratory diseases are caused by extracellular bacterial pathogens; however, two very important lung infections are due to intracellular pathogens, Legionnaires' disease and tuberculosis. Legionnaires' disease remains problematic due to our inability to predict where sporadic epidemics will occur and the speed at which the bacterium debilitates its victims. The development of better methods for prevention would greatly alleviate public concern and the economic impacts of eradication efforts where infections occur. Legionella, the causative agent of Legionnaires' disease, has been shown to replicate within eukaryotic cells both during disease and in the environment. During disease these bacteria are found primarily within macrophages, though they have the ability to enter and survive within a number of different mammalian cell types. In the environment Legionella replicate within free-living protozoa. Thus, the ability to enter into host cells successfully and efficiently is critical to the ability of Legionella to survive. The process by which Legionella gains access to the intracellular environment involves a number of steps; including, finding an appropriate host cell, adherence, signal transduction, entry and initial survival. Unless Legionella accomplishes each of these steps properly, few viable bacteria will be observed intracellularly and reduced intracellular replication may occur. However, the importance of each of these individual steps in the pathogenesis of Legionella is unclear. Herein we discuss the potential mechanisms of entry by Legionella into host cells, a critical early event in the production of Legionnaires' disease. PMID- 11779714 TI - Interphase fluorescence in-situ hybridization in the diagnosis of bladder cancer. AB - Interphase FISH is a technique that uses fluorescent molecules to detect chromosomes or specific regions of DNA. It is a rapid and powerful technique for detection of cytogenetic abnormalities in malignant cells independent of their cell cycle status. Using variety of pericentromeric and locus-specific probes, numerical chromosomal changes (aneusomy) as well as loss or gain/amplification of specific genetic regions can be detected in clinical samples. Numerous studies have identified genetic alterations at the DNA level, occurring in the pathogenesis of variety of human neoplasms including bladder cancer, some of which can be used for detection, prognosis, and as intermediate endpoints for evaluating the response to therapy. Recently, sensitivity and specificity of a multicolor FISH assay consisting of four probes (3, 7, 17 and 9p21) was analyzed in several prospective and retrospective studies. The data suggest that this method applicable to voided urine specimens may allow safe extension of the interval between cystoscopies in routine surveillance of patients with transitional cell carcinoma of the bladder. FISH analysis of cells isolated from bladder washings or voided urine is also holding promise for monitoring of treatment outcome and predicting recurrence and progression of the disease. Therefore, this technique can be an important aid in the efforts to reduce mortality from transitional cell carcinoma of the bladder, since it increases our ability to prevent progression to incurable muscle invasive disease. PMID- 11779715 TI - Abl: mechanisms of regulation and activation. AB - The Abl non-receptor tyrosine kinase has been implicated in a wide variety of cellular processes, yet its function and regulation remain poorly understood. Abl has resisted complete understanding not due to lack of interest, but due to the complexity of its overall structure and the corresponding complexity and diversity of its biological activities in the cell. Although Abl consists of many familiar modules with well-understood activities, the ways in which these modules interact are manifold and defy simple categorization. A picture now emerges in which Abl can be potentially regulated in many ways: by phosphorylation, by intramolecular interaction, by interaction with a variety of other proteins, by subcellular localization. Far from being a simple on-off switch, it appears that Abl is better understood as existing in a complex and dynamic equilibrium of states, an equilibrium that can be affected by many signaling inputs. In this review we will discuss the various ways in which the kinase activity of Abl can be regulated; other recent reviews have discussed the larger issue of possible biological roles of Abl (1-3). PMID- 11779716 TI - Hypoglycemia and embryonic heart development. AB - Abnormal embryonic development is a complication of the diabetic pregnancy, and heart defects are among the most common and detrimental congenital malformations of the diabetic embryopathy. Hypoglycemia is a common side effect of diabetes therapy and is a potential teratogen. An association between hypoglycemia and congenital defects has been difficult to demonstrate in humans, but in vivo and in vitro animal studies have illustrated the importance of glucose as a substrate for normal development. Hypoglycemia alters embryonic heart morphology, producing abnormal looping and chamber expansion, decreased myocardial thickness, disorganized layers, and decreased overall size. Hypoglycemia decreases embryonic heart rate and vascularity, and it alters embryonic heart metabolism by increasing glucose uptake and glycolysis. Hypoglycemia also affects protein expression in the embryonic heart, increasing the expression of glucose regulated proteins, hexokinase, and glucose transport protein. Thus, hypoglycemia interferes with normal cardiogenesis and alters morphology, function, metabolism, and expression of certain proteins in the developing heart. It is likely that these factors contribute to heart defects observed in the diabetic embryopathy, but the definitive link has yet to be made. Future studies are expected to further elucidate mechanisms mediating hypoglycemia-induced cardiac dysmorphogenesis. PMID- 11779717 TI - Protein microarray technology. AB - This review summarizes the major activities in the field of protein microarray technology. A short summary of the theoretical concepts of miniaturized ligand binding assays explains why such microspot assays represent the most sensitive approaches for capture-target assays. The main focus of this review is centered on the applications using miniaturized and parallelized protein binding assays which rely on the product formation between immobilized capture molecules and their corresponding target molecules which are present in the sample. These types of ligand binding assays are useful tools for protein identification, quantification and protein affinity studies. Protein identification and quantification assays have a great potential in the field of diagnostics and proteomics where many different protein markers which are present in complex samples have to be analyzed in parallel. Protein affinity assays can be used to analyze interactions between proteins such as antibodies, receptors or enzymes with other proteins, peptides, low molecular weight compounds, oligosaccharides or DNA. Different applications of protein microarray-based assays and their huge potential for diagnostic and proteomic approaches will be discussed. PMID- 11779718 TI - Nitrocellulose: a tried and true polymer finds utility as a post-genomic substrate. AB - High-throughput techniques for genomics and proteomics differ greatly from traditional bio-molecular research techniques in the amount of data that can be obtained from a given experiment. However, many of these novel techniques rely heavily on the traditional concepts of molecular immobilization followed by hybridization, binding or analysis. These concepts, which predate even traditional blotting techniques, have become so widely used that the complexity of their fundamental precepts is often overlooked. In this review, we explore the history and use of one of the most common immobilization surfaces, nitrocellulose. This unique polymer has been used as a surface in biological research for more than 6 decades, and continues to find utility in the post genomic era with high-throughput techniques. PMID- 11779719 TI - Bax and BH3-domain-only proteins in p53-mediated apoptosis. AB - Activation of mitochondria-mediated apoptosis represents a major anti-tumor response of p53. One of the mechanisms for p53 to induce mitochondria-mediated cell death events is to activate genes that are directly involved in the initiation of mitochondria-induced apoptosis. Among them are Bcl-2 family members, Noxa, PUMA, and Bax. They have been shown to be direct targets in p53 mediated apoptosis. The Bax protein belongs to the multidomain Bcl-2 family, while Noxa and PUMA are BH3-domain-only proteins. This review focuses on discussing the function of these protein in p53-mediated apoptosis and how they contribute to the decision making of p53 response: growth arrest or apoptosis. PMID- 11779720 TI - Glutaminase and the control of airway pH: yet another problem for the asthmatic lung? PMID- 11779721 TI - What caused the screech, whamity, bang, and thump? PMID- 11779722 TI - Congestive heart failure. PMID- 11779723 TI - Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. AB - Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin intolerant patients over and above what can be achieved by glucocorticosteroids. PMID- 11779724 TI - Effect of budesonide on the perception of induced airway narrowing in subjects with asthma. AB - The perception of bronchoconstriction may be modulated by airway inflammation. However, the effect of inhaled corticosteroid (ICS) treatment on perception in subjects with asthma has received limited study. The aim of this study was to determine the effect of inhaled budesonide on the perception of breathlessness induced by histamine challenge. Thirty-five subjects with poorly controlled asthma were randomized to receive budesonide (1,600 or 3,200 microg/d) for 8 wk, followed by 8 wk at 1,600 microg/d and subsequent downtitration according to a clinical algorithm. Borg scores were recorded during histamine challenges performed at baseline and at 8, 16, 24, 48, and 72 wk. Perception was estimated as the slope of Borg/% fall FEV(1). The Borg/FEV(1) slope increased significantly after 8 wk of budesonide (0.09 [0.08-0.12] to 0.15 [0.11-0.19], p = 0.002), and remained increased compared with baseline values at all subsequent visits. There were no significant differences in Borg/ FEV(1) slope between subjects who were and were not taking ICS at study entry. The magnitude of change in the Borg/FEV(1) slope did not differ significantly between treatment groups and was not related to changes in baseline FEV(1), airway hyperresponsiveness, blood eosinophils, or serum eosinophil cationic protein (ECP). We conclude that treatment with budesonide enhances the perception of airway narrowing, but the effect is unrelated to budesonide dose, or to changes in circulating eosinophil markers. PMID- 11779725 TI - Increases in allergen-specific IgE in BAL after segmental allergen challenge in atopic asthmatics. AB - IgE is important in both early and late allergic responses. Increases in the numbers of RNA transcripts coding for IgE have been observed in the bronchial mucosa of asthmatics and in the nasal mucosa of hay fever patients both during natural allergen exposure and after nasal allergen challenge, suggesting that IgE may be synthesized locally in the mucosa. In this study we have examined bronchoalveolar lavage (BAL) taken before and 24 h after bronchoscopic segmental allergen challenge from 18 atopic asthmatic patients, looking for evidence of increases in IgE protein. Allergen-specific IgG and total and allergen-specific IgE were measured in BAL using a fluoroenzyme immunoassay. There was a significant increase in allergen-specific IgE (Ku/L) in the BAL after allergen challenge [before [median (interquartile range)] 0 (0, 0); after 0.35 (0, 1.87): p = 0.009] which was not observed for allergen-specific IgG (p = 1.0) or for IgE specific to an allergen to which the subject was sensitized but was not used for provocation (p = 1.0). Correction for corresponding increases in total IgE, albumin, and urea in BAL did not affect the observed changes in allergen-specific IgE. These data indicate that allergen provocation results in a selective local accumulation of isotype-specific and allergen-specific IgE antibody within the bronchi, independent of alterations in circulating IgE. PMID- 11779726 TI - Heparin inhibits hyperventilation-induced late-phase hyperreactivity in dogs. AB - Inhalation of heparin attenuates hyperventilation-induced bronchoconstriction in humans and dogs. The purpose of this study was to determine whether heparin inhibits the late-phase response to hyperventilation, which is characterized by increased peripheral airway resistance (RP), eicosanoid mediator production, neutrophilic/ eosinophilic inflammation, and airway hyperreactivity (AHR) at 5 h after dry air challenge (DAC). Fiberoptic bronchoscopy was used to record RP and airway reactivity (DeltaRP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured approximately 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (approximately 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C(4), LTD(4), and LTE(4) and prostaglandin (PG)D(2), and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by approximately 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC(4), LTD(4), and LTE(4) and PGD(2), and abolished AHR. We conclude that heparin inhibits hyperventilation-induced late-phase changes in peripheral airway function, and does so in part via the inhibition of eosinophil migration and eicosanoid mediator production and release. PMID- 11779727 TI - Improvement in spirometry following lung volume reduction surgery: application of a physiologic model. AB - According to a previously published theoretical model of emphysema, the ratio of RV to TLC (RV/TLC) reflects the size mismatch between the hyperinflated lungs in the disease and the surrounding chest. The model suggests that RV/TLC is an important predictor of improvement in FVC and that increased FVC is an important determinant of increased FEV(1) after lung volume reduction surgery (LVRS). We tested these predictions in 13 patients undergoing LVRS, in whom we made detailed measurements of lung mechanics. Using stepwise regression, we found that RV/TLC was the only preoperative independent predictor of the increase in FVC. Seventy percent of the increase in FEV(1) was attributable to increased FVC, with the remainder due to increased FEV(1)/FVC. In a separate group of 78 LVRS patients evaluated with standard preoperative pulmonary function tests, RV/TLC again was found to correlate with the increase in FVC, and changes in FEV(1) were also due largely to changes in FVC. However, RV/TLC was not predictive of the increase in FEV(1) among the group of 78 patients, because FEV(1)/FVC in patients with a low preoperative RV/TLC often increased despite little change in FVC. These findings support the proposed mechanism for increased FVC following LVRS. They also illustrate the limitations of the model, and suggest further hypotheses for selecting patients who may benefit from surgery. PMID- 11779728 TI - Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia. AB - Results of routine microbiologic cultures of specimens obtained before the onset of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients might help to identify the causative microorganisms and thus to select effective initial antimicrobial therapy. To test this hypothesis, we prospectively studied 125 consecutive VAP episodes for which the causative microorganisms were determined using bronchoscopic techniques. Upon entry into the study, each patient's hospital chart was reviewed and culture results of all previously obtained microbiologic specimens were recorded (mean number +/- SD per patient, 45 +/- 38). A total of 220 microorganisms were cultured at significant concentrations (> or = 10(3)/10(4) colony-forming units [cfu]/ml) from bronchoscopic specimens and considered responsible for pneumonia. Of these 220 organisms, only 73 (33%) were recovered before VAP onset, sometimes from multiple sites in the same patient but mainly from prior respiratory secretion cultures (n = 53). Also previously isolated were 342 organisms that were not responsible for VAP, making prospective identifications of the true pathogens difficult. Among the 102 episodes for which prior respiratory secretion culture results had been obtained (mean time before VAP onset, 8 +/- 9 d), all the organisms ultimately responsible for pneumonia were previously recovered from only 36 (35%) of these specimens. Based on these data, the contribution of routine microbiologic specimens in guiding initial antimicrobial therapy decisions for patients with suspected VAP appears limited. PMID- 11779729 TI - Oscillations and noise: inherent instability of pressure support ventilation? AB - Pressure support ventilation (PSV) is almost universally employed in the management of actively breathing ventilated patients with acute respiratory failure. In this partial support mode of ventilation, a fixed pressure is applied to the airway opening, and flow delivery is monitored by the ventilator. Inspiration is terminated when measured inspiratory flow falls below a set fraction of the peak flow rate (flow cutoff); the ventilator then cycles to a lower pressure and expiration commences. We used linear and nonlinear mathematical models to investigate the dynamic behavior of pressure support ventilation and confirmed the predicted behavior using a test lung. Our mathematical and laboratory analyses indicate that pressure support ventilation in the setting of airflow obstruction can be accompanied by marked variations in tidal volume and end-expiratory alveolar pressure, even when subject effort is unvarying. Unstable behavior was observed in the simplest plausible linear mathematical model and is an inherent consequence of the underlying dynamics of this mode of ventilation. The mechanism underlying the observed instability is "feed forward" behavior mediated by oscillatory elevation in end-expiratory pressure. In both mathematical and mechanical models, unstable behavior occurred at impedance values and ventilator settings that are clinically realistic. PMID- 11779730 TI - Antioxidant protection of propofol and its recycling in erythrocyte membranes. AB - alpha-Tocopherol is a potent antioxidant that effectively protects biological membranes against oxidative injury through coordination with ascorbic acid. Because propofol has a phenolic structure similar to that of alpha-tocopherol, this intravenous anesthetic may also have similar antioxidant activity. To test this hypothesis, the effect of propofol on oxidative injury of human erythrocytes was examined. Propofol inhibited oxidative hemolysis and cis-parinaric acid oxidation in erythrocyte membranes (ED(50) = 6 microM). Although ascorbic acid alone has no appreciable effect, the protective effect of propofol was enhanced by ascorbic acid. An electron spin resonance (ESR) study showed that propofol derived radicals (g = 2.005) were continuously generated during the oxidation of erythrocyte membranes by an ascorbic acid-inhibitable mechanism. These and other results suggest that propofol interacts with ascorbic acid, thereby exhibiting potent antioxidant activity in and around membranes as does alpha-tocopherol. Kinetic analysis revealed that propofol increased the membrane fluidity of erythrocytes, thereby increasing their resistance to physical and hemodynamic stress. Further, a greater preservation of red blood cell counts was seen after surgery with propofol compared with conventional sevoflurane anesthesia. Thus, propofol may protect erythrocytes against both oxidative and physical stress, indicating its potential as an efficient and safe antioxidant. PMID- 11779731 TI - Obstructive apnea during sleep is associated with peripheral vasoconstriction. AB - Obstructive apnea during sleep is associated with a substantial transient blood pressure elevation. The mechanism of this pressor response is unclear. In this study we measured muscle sympathetic nerve activity (MSNA), mean arterial pressure (Psa), and mean limb blood velocity as an index of blood flow (MBV, Doppler) and calculated changes in limb vascular resistance during and after apneas during both wakefulness and sleep in patients with the obstructive sleep apnea syndrome. Immediately postapnea during sleep Psa increased significantly compared with the earlier stages of apnea and this was preceded by a rise of MSNA (n = 5). In contrast to blood pressure, MBV remained unchanged. Because resistance = blood pressure/blood flow, limb vascular resistance increased by 29 +/- 8% from late apnea to postapnea (n = 7, p < 0.002). Voluntary breathhold maneuvers during room air exposure evoked similar responses (n = 10). Supplemental oxygen administered via nonrebreather face mask attenuated the MSNA and vasoconstrictor responses to obstructive (n = 2) and voluntary apneas (n = 10). Our data suggest that obstructive apneas in patients with the obstructive apnea syndrome are accompanied by transient limb vasoconstriction. This vasoconstrictor response appears to be, at least in part, mediated by the sympathetic nervous system and may be linked to hypoxia. PMID- 11779732 TI - Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. AB - Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality; however, some patients with OSA do not develop cardiovascular disease even in the presence of severe nocturnal oxygen desaturations. Vascular endothelial growth factor (VEGF) is a hypoxia-sensitive glycoprotein stimulating neoangiogenesis. We hypothesized that VEGF production is increased in OSA because of repetitive nocturnal hypoxia. Three different groups were investigated: 10 OSA patients with severe nighttime hypoxia (Group A), 10 OSA patients with moderate hypoxia (Group B), and 10 healthy volunteers (Group C). Serum levels of VEGF were measured by ELISA from peripheral venous blood samples obtained at 7 AM. Group A had significantly (p < 0.01) increased VEGF serum levels when compared with Group B and Group C (mean +/- SEM: 410 +/- 77 pg/ml versus 224 +/- 38 pg/ml and 245 +/- 61 pg/ml). The degree of nocturnal oxygen desaturation in OSA significantly correlated with the VEGF concentrations (r = 0.67, p < 0.01). In conclusion, serum levels of VEGF are elevated in severely hypoxic patients with OSA and are related to the degree of nocturnal oxygen desaturation. This might constitute an adaptive mechanism to counterbalance the emergence of OSA-related cardiovascular disease. PMID- 11779733 TI - Pharyngeal pressure and flow effects on genioglossus activation in normal subjects. AB - Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnea syndrome. Substantial data support the role of local mechanisms in mediating pharyngeal dilator muscle activation in normal humans during wakefulness. Using a recently reported iron lung ventilation model, we sought to determine the stimuli modulating genioglossus activity, dissociating the influences of pharyngeal negative pressure, from inspiratory airflow, resistance, and CO(2). To achieve this aim, we used two gas densities at several levels of end-tidal CO(2) and a number of intrapharyngeal negative pressures. The correlations between genioglossus electromyography (GGEMG) and epiglottic pressure across a breath remained robust under all conditions (R values range from 0.71 +/- 0.07 to 0.83 +/- 0.05). In addition, there was no significant change in the slope of this relationship despite variable gas density or CO(2) levels. Although flow also showed strong correlations with genioglossus activity, there was a significant change in the slope of the GGEMG/flow relationship with altered gas density. For the group averages across conditions (between breath analysis), the correlation with GGEMG was robust for negative pressure (R(2) = 0.98) and less strong for other variables such as flow and resistance. These data suggest that independent of central pattern generator activity, intrapharyngeal negative pressure itself modulates genioglossus activity both within breaths and between breaths. PMID- 11779734 TI - "Tightness" sensation of asthma does not arise from the work of breathing. AB - Asthma evokes several uncomfortable sensations including increased "effort to breathe" and chest "tightness." We have tested the hypotheses that "effort" and "tightness" are due to perception of increased work performed by the respiratory muscles. Bronchoconstriction was induced by inhaled methacholine in 15 subjects with mild asthma (FEV(1)/FVC baseline = 81.9% +/- 5.8; bronchoconstriction = 64.0% +/- 8.6). To relieve the work of breathing, and thereby minimize activation of respiratory muscle afferents and motor command, subjects were mechanically ventilated. Subjects separately rated effort to breathe and tightness during mechanical ventilation and during spontaneous breathing. Bronchoconstriction produced elevated end-expiratory lung volume (279 +/- 62 ml); in a control study, end-expiratory lung volume was increased equally in the absence of bronchoconstriction by increasing end-expiratory pressure. During bronchoconstriction, ratings of effort were greater during spontaneous breathing than during mechanical ventilation (p < 0.05). Ratings of tightness were unchanged by the absence of respiratory muscle activity (p = 0.12). Hyperinflation alone did not produce tightness or effort. We conclude that tightness is not related to the increase in respiratory work during bronchoconstriction. PMID- 11779735 TI - Abnormal lung function in healthy preterm infants. AB - The aim of this study was to assess the consequences of preterm birth for the functional development of the lungs. We studied 32 healthy preterm infants (gestational age 25 to 33 wk at birth) and 53 healthy full-term infants (37 to 42 wk) at the same mean postmenstrual age of 40 wk with a multibreath nitrogen washout technique to assess functional residual capacity (FRC), gas mixing efficiency, and dead space and with the single-breath occlusion technique to calculate compliance and resistance of the respiratory system. Twenty of the preterm infants were also assessed with the same methods at 34.2 (32 to 37) wk. At the same postmenstrual age the preterm infants had lower FRC/kg body weight, lower specific compliance, impaired gas mixing efficiency, and higher total and dead space ventilation/kg than the full-term infants. Specific compliance and specific conductance decreased but gas mixing efficiency increased from 34 to 40 wk. We conclude that premature exposure to extrauterine conditions changes lung function. Preterm infants showed signs of dysfunction of the terminal respiratory units and higher elastic recoil than infants who spent the corresponding time for development in utero. It is suggested that preterm birth per se affects alveolarization and formation of elastic tissue in the lungs. PMID- 11779736 TI - Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro. AB - Vascular endothelial growth factor (VEGF) increases vascular permeability and is important in pleural effusion formation. In studies using transforming growth factor beta (TGF-beta) to produce pleurodesis, we observed that although TGF-beta was more effective than talc or doxycycline, it induced transient production of large pleural effusions. We hypothesized that TGF-beta stimulates VEGF production in pleural tissues in vivo, and by mesothelial cells in vitro. New Zealand White rabbits (n = 33) were given TGF-beta(2) (1.7 or 5.0 microg), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intrapleurally. Pleural fluid was collected at 24 h. Intrapleural injection of TGF-beta(2) induced a dose-dependent increase in VEGF production. The pleural fluid VEGF level was 2-fold higher in rabbits given 5.0 microg of TGF-beta(2) than in those given 1.7 microg of TGF-beta(2) and 3 fold higher than in those given buffer. VEGF levels were higher after the injection of TGF-beta(2) than after administration of talc or doxycycline. The pleural fluid VEGF correlated significantly with the volume of pleural effusions (r = 0.79, p < 0.00001). In vitro, TGF-beta(2) stimulated a dose-dependent increase in VEGF production from murine pleural mesothelial cells. At 4 and 24 h, TGF-beta(2), but not talc or doxycycline, induced a significant increase in VEGF, when compared with controls. The mesothelial cell VEGF production was significantly reduced by anti-TGF-beta antibody in the TGF-beta(2), talc, and control (buffer and medium) groups. In conclusion, mesothelial cells are an important source of VEGF. TGF-beta increases the VEGF production by mesothelial cells in vivo and in vitro. PMID- 11779737 TI - Molecular pathways of monocyte emigration into the alveolar air space of intact mice. AB - The adhesive interactions involved in monocyte recruitment to the alveolar space in vivo are only poorly defined. To study these interactions, we used a recently developed mouse model that allowed the separation and quantification of freshly recruited monocytes, resident alveolar macrophages (rAM), neutrophils, and lymphocytes in the bronchoalveolar compartment by fluorescence activated cell sorting technology. In these mice, the combined intratracheal administration of the monocyte chemoattractant JE/monocyte chemotactic protein (MCP)-1 and low dose Escherichia coli lipopolysaccharide (LPS) induces a self-limiting pulmonary inflammatory response, characterized by well-controlled sequelae of both neutrophil and monocyte emigration into the alveolar space. In contrast, challenge with JE/MCP-1 provokes the emigration only of monocytes in the absence of lung inflammation. Using an array of function-blocking monoclonal antibodies (mAb) (anti-CD11a, -CD11b, -CD18, -CD49d, -CD54, and -CD106), we characterized the adhesive interactions underlying the transendothelial and transepithelial leukocyte traffic in intact animals. Alveolar monocyte recruitment elicited by JE/MCP-1 alone was strictly dependent on CD11b/CD18, CD54, and CD49d, and partly dependent on CD11a, but not dependent on CD106. In response to JE/MCP-1 plus E. coli LPS, we observed additional engagement of CD11a and CD106 for enhanced alveolar monocyte transmigration. Comigrating neutrophils were found to primarily utilize CD11b, CD18, and CD54, but not CD49d, CD106, or, surprisingly, CD11a. This contrasted with the effect of CD11a on alveolar challenge with macrophage inflammatory protein (MIP)-1alpha instead of JE/MCP-1. In conclusion, we found that in an intact mouse model allowing detailed phenotyping of leukocyte traffic into the alveolar space, the molecular pathways involved in JE/MCP-1-driven monocyte efflux differed under noninflammatory and inflammatory (presence of LPS) conditions. Moreover, the profile of adhesive interactions underlying the monocyte efflux differed from that characterizing neutrophil trafficking. PMID- 11779738 TI - Expression and activity of pH-regulatory glutaminase in the human airway epithelium. AB - Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media pH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-alpha. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 microM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 microM [14-1,220], n = 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation. PMID- 11779739 TI - A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model. AB - Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis. PMID- 11779740 TI - Linear dimensions of the upper airway structure during development: assessment by magnetic resonance imaging. AB - The upper airway undergoes progressive changes during childhood. Using magnetic resonance imaging (MRI), we studied the growth relationships of the tissues surrounding the upper airway (bone and soft tissues) in 92 normal children (47% males; range, 1 to 11 yr) who underwent brain MRI. None had symptoms of sleep disordered breathing or conditions that impacted on their upper airway. MRI was performed under sedation. Sequential T1-weighted spin echo sagittal and axial sections were obtained and analyzed on a computer. We measured lower face skeletal growth along the midsagittal and axial oropharyngeal planes. In the midsagittal plane the mental spine-clivus distance related linearly to age (r = 0.86, p < 0.001). Along this axis, the dimensions of tongue, soft palate, nasopharyngeal airway, and adenoid increased with age and maintained constant proportion to the mental spine-clivus distance. Similarly, a linear relationship was noted for mandibular growth measured along the intermandibular line on the axial plane and age (r = 0.78, p < 0.001). In addition, the intertonsillar, tonsils, parapharyngeal fat pads, and pterygoids widths maintained constant proportion to intermandibular width with age. We conclude that the lower face skeleton grows linearly along the sagittal and axial planes from the first to the eleventh year. Our data indicate that soft tissues, including tonsils and adenoid, surrounding the upper airway grow proportionally to the skeletal structures during the same time period. PMID- 11779741 TI - Randomized controlled study of an oral jaw-positioning appliance for the treatment of obstructive sleep apnea in children with malocclusion. AB - To evaluate the clinical usefulness and tolerability of an oral jaw-positioning appliance in the treatment of obstructive sleep apnea syndrome in children, we studied 32 patients (mean age, 7.1 +/- 2.6 yr; 20 males) with symptoms of obstructive sleep apnea, malocclusion, and a baseline apnea index > 1 event/h. A group of 19 subjects was randomly assigned to a 6-mo trial of an oral appliance; the remainder acted as control subjects. At baseline and after the trial all patients underwent physical examination, a standard polysomnography, and orthodontic assessment. A modified version of the Brouillette questionnaire related to obstructive sleep apnea symptoms was administered to parents before and after the trial and a clinical score was calculated. Of the 32 subjects enrolled, 4 treated subjects and 5 control subjects were lost to follow-up. Polysomnography after the trial showed that treated subjects all had significantly lower apnea index (p < 0.001) and hypopnea index values (p < 0.001) than before the trial, whereas in untreated control subjects these values remained almost unchanged. Clinical assessment before and after treatment showed that in 7 of the 14 subjects (50%) the oral appliance had reduced (a fall of at least 2 points in the respiratory score) and in 7 had resolved the main respiratory symptoms, whereas untreated patients continued to have symptoms. In conclusion, treatment of obstructive sleep apnea syndrome with an oral appliance in children with malocclusion is effective and well tolerated. PMID- 11779742 TI - Successful treatment of endogenous lipoid pneumonia due to Niemann-Pick Type B disease with whole-lung lavage. AB - In Type B Niemann-Pick disease, progressive pulmonary infiltration is a major cause of morbidity and mortality, although the disease is usually diagnosed before adulthood in other organ systems. To date, no successful treatment of pulmonary involvement by Niemann-Pick disease has been documented. We describe the case of a patient with Niemann-Pick Type B disease who presented with extensive endogenous lipoid pneumonia and life-threatening hypoxia following bypass grafting for severe coronary artery disease. A surgical lung biopsy at the time of grafting revealed characteristic histology and ultrastructural features of Niemann-Pick disease, with confirmatory findings in biochemical studies. Because of the severity of the patient's symptoms, bilateral whole-lung lavage was undertaken, leading to symptomatic improvement, lessening of parenchymal opacification on high-resolution computed tomographic scanning, and a marked improvement in resting arterial oxygen tension while breathing air to 10.3 kPa from 8.4 kPa. Whole-lung lavage may be a potentially useful modality of treatment for patients with pulmonary involvement by Niemann-Pick Type B disease. PMID- 11779743 TI - Inflammatory markers in bacterial exacerbations of COPD. PMID- 11779744 TI - The science of designing ethical CPAP trials. PMID- 11779745 TI - The "gold standard" for past asbestos exposure. PMID- 11779746 TI - Steroids cause osteoporosis. PMID- 11779748 TI - Mesenchymal precursor cells. PMID- 11779749 TI - Could inflammatory arthritis be triggered by progenitor cells in the joints? PMID- 11779750 TI - A case of weak muscles. AB - BACKGROUND: Gut involvement in inflammatory myositis is rare but causes significant morbidity and mortality. CASE REPORT: A case of eosinophilic gastroenteritis and polymyositis occurring in the same patient is described. The interface of visceral and striated muscle involvement is discussed. The pathophysiology of eosinophilic gastroenteritis and the spectrum of gastrointestinal involvement in inflammatory myositis are also discussed. RESULTS: Both gastrointestinal and skeletal muscle symptoms improved with immunosuppression, suggesting a possible common underlying mechanism. PMID- 11779751 TI - Insoluble and soluble immune complexes activate neutrophils by distinct activation mechanisms: changes in functional responses induced by priming with cytokines. AB - BACKGROUND: Rheumatoid synovial fluid contains both soluble and insoluble immune complexes that can activate infiltrating immune cells such as neutrophils. OBJECTIVES: To determine if these different complexes activate neutrophils through similar or different receptor signalling pathways. In particular, to determine the circumstances which result in the secretion of tissue damaging reactive oxygen metabolites and granule enzymes. METHODS: Blood neutrophils were incubated with synthetic soluble and insoluble immune complexes and the ability to generate reactive oxidants tested by luminescence or spectrophotometric assays that distinguished between intracellular and extracellular production. Degranulation of myeloperoxidase and lactoferrin was determined by western blotting. The roles of FcgammaRII (CD32) and FcgammaRIIIb (CD16) were determined by incubation with Fab/F(ab')(2) fragments before activation. The effect of cytokine priming was determined by incubation with GM-CSF. RESULTS: Insoluble immune complexes activated unprimed neutrophils, but most of the oxidants produced were intracellular. This activation required FcgammaRIIIb, but not FcgammaRII function. Soluble complexes failed to activate unprimed neutrophils but generated a rapid and extensive secretion of reactive oxygen metabolites when the cells were primed with granulocyte-macrophage colony stimulating factor (GM CSF). This activity required both FcgammaRII and FcgammaRIIIb function. Insoluble immune complexes activated the release of granule enzymes from primed or unprimed neutrophils, but the kinetics of release did not parallel those of secretion of reactive oxygen metabolites. Only primed neutrophils released enzymes in response to soluble complexes. CONCLUSIONS: Soluble and insoluble immune complexes activate neutrophils by separate receptor signalling pathways. Profound changes in neutrophil responsiveness to these complexes occur after cytokine priming. PMID- 11779752 TI - The rheumatoid arthritis articular damage score: first steps in developing a clinical index of long term damage in RA. AB - OBJECTIVE: To design and validate a clinical method for scoring irreversible long term articular damage in rheumatoid arthritis (RA). METHODS: The rheumatoid arthritis articular damage score (RAAD score) is based on examination of 35 large and small joints. Concise definitions were formulated to score each joint on a three point scale (0, no irreversible damage; 1, partially damaged; 2, severe damage, ankylosis, or prosthesis). The RAAD score was determined for 121 patients with RA with a large range of disease duration. Interobserver agreement was studied in 39 patients scored by three observers. Data on disease duration, Health Assessment Questionnaire, disease activity score, and Larsen score were collected for 121, 78, 47, and 45 patients, respectively. RESULTS: The RAAD score correlated well with the Larsen score (r(s)=0.81) and disease duration (r(s)=0.68) and (as intended) not with disease activity (r(s)=0.10). Good interobserver agreement was found for total scores and individual joints. The wide range of RAAD scores for patients with the same disease duration suggested good discriminating power, especially after >10 years. CONCLUSION: The RAAD score is a quick and feasible method for measuring the long term articular damage in large RA populations. It has good reliability and construct validity and deserves further study to assess its discriminant validity. PMID- 11779753 TI - Influence of elastic bandage on knee pain, proprioception, and postural sway in subjects with knee osteoarthritis. AB - OBJECTIVES: To investigate whether a "standard" sized (that is, a size that would be prescribed by a physiotherapist) elastic bandage (S-bandage) around the knee of subjects with knee osteoarthritis (OA) would, in the short term (a) reduce pain, (b) improve knee joint proprioception, and (c) decrease sway in comparison with a looser (L-bandage). METHODS: In a cross over, within-subject study, 68 subjects (49 women, 19 men; mean age 67.1, range 36-87) with symptomatic and radiographic knee OA were randomly assigned to either an S-bandage or an L bandage. Two weeks later they were assigned to the opposite bandage size. Knee pain (10 cm visual analogue scale (VAS)), knee proprioception, and static postural sway were assessed for each bandage two weeks apart. During each visit assessments were performed at baseline, after 20 minutes of bandage application, and immediately after bandage removal. RESULTS: The S-bandage did not have any effect on knee pain, proprioception, or postural sway. The L-bandage reduced knee pain significantly (pre-bandage application: median VAS 4.36, IQR 3.84 -4.90; after 20 minutes of bandage application: median VAS 3.80, IQR 3.3-4.3, p<0.001), improved static postural sway (pre-bandage: median sway 4.50, IQ range 3.5-6.4; bandage applied: median sway 4.45, IQ range 3.4-6.3, p=0.027), but had no significant influence on knee proprioception. CONCLUSIONS: In subjects with knee OA application of an elastic bandage around the knee can reduce knee pain and improve static postural sway. This outcome depends on the size of applied bandage. PMID- 11779754 TI - Familial systemic lupus erythematosus: the role of genetic and environmental factors. AB - OBJECTIVE: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). METHODS: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non consanguineous relatives. RESULTS: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. CONCLUSION: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts. PMID- 11779755 TI - Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. AB - BACKGROUND: The use of oral corticosteroids (CS) is one of the most common causes of iatrogenic osteoporosis. Recently, therapeutic guidelines dealing with the skeletal complication of CS have been published. OBJECTIVE: To evaluate how CS are used in the community and the frequency of active intervention against corticosteroid induced osteoporosis in daily clinical practice. MATERIAL AND METHODS: After approval by the Committee on Medical Ethics and the Data Protection Commission all prescriptions for CS which were filled by pharmacies in the northeast area of Iceland (population 26,664) during a two year period were collected. Thereafter, clinical information was obtained from medical records at the healthcare centres and from the local hospital. Patients who were taking CS for at least three months a year or for repeated periods (for a total of three months annually) were included in the study. These patients also received a questionnaire about hormone replacement therapy, bisphosphonates, and dietary consumption of calcium and vitamin D. RESULTS: A total of 191 patients were included in the study or 0.7% of the population. Their mean age was 66 years (17 93) and 106/191 (55%) were women. Only 63 (33%) patients had no registered complication due to the treatment, according their medical records. Thirty nine (20%) patients had had an osteoporosis related fracture and 50 (26%) of the patients had presumed CS induced osteoporosis. A total of 52% patients were receiving supplementary vitamin D (fish liver oil) and 37% were taking calcium tablets regularly, while 91% of the patient group were consuming milk products regularly. Only 17 (9%) patients were taking bisphosphonates and 18/81 (22%) of the postmenopausal women were receiving hormone replacement therapy. CONCLUSIONS: Relatively few patients receiving long term treatment with CS are also receiving primary prevention against CS induced osteoporosis, although several patients are taking vitamin D and calcium tablets. Specific treatment against osteoporosis was in most cases instituted secondary to osteoporotic complications. Thus although there are available treatment alternatives against CS induced osteoporosis, the doctors who prescribed CS did not make use of this form of treatment for their patients. PMID- 11779756 TI - Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis. AB - OBJECTIVE: To describe the treatment of polymyositis (PM) and dermatomyositis (DM) with prednisone (PRED) and cyclosporin A (CSA) alone or associated with intravenous immunoglobulin (IVIg) and plasmapheresis (PEX). METHODS: Between 1992 and 1999 CSA and PRED were used to treat 20 patients with idiopathic myositis (12 with DM, eight with PM), diagnosed according to the Bohan and Peter criteria. In patients with refractory or relapsed disease, IVIg was added alone (seven cases) or synchronised with PEX (six cases). A standardised protocol was used to evaluate the patients, and assess disease activity and treatment response. RESULTS: Despite a transient response to PRED and CSA in 16/20 cases, this combination did not induce full remission in 13/20 cases, which led to the IVIg trial with or without PEX. Patients receiving PRED and CSA plus IVIg had a significantly higher probability of maintaining complete remission at the end of the four year follow up period than those treated with PRED and CSA alone (p<0.001). No further benefit was added by the PEX. The presence of arthritis significantly correlated with a poorer response to treatment (p<0.05). Adverse effects were gingival hyperplasia (one patient) and transient renal dysfunction (one). CONCLUSIONS: This open study suggests that combined treatment with PRED, CSA, and IVIg is useful in patients with myositis, even those with refractory or relapsed disease; no increase in the number or type of side effects is seen. PMID- 11779757 TI - Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arthritis: clinical and laboratory characteristics. AB - OBJECTIVE: To screen for amyloid and to assess associated clinical and laboratory characteristics in Egyptian patients with rheumatoid arthritis (RA). METHODS: Abdominal subcutaneous fat aspirates were consecutively collected from 112 patients (103 women, nine men) having RA for five years or more. To detect amyloid, fat smears were stained with Congo red and the concentration of amyloid A protein in fat tissue was measured. Clinical, radiological, and laboratory characteristics of the patients were assessed. RESULTS: Amyloid was detected in eight (7%) of the fat smears stained with Congo red. Compared with the Congo red stain, the sensitivity for detecting amyloid by measurement of amyloid A protein in fat tissue was 75% and the specificity was 100%. The amount of amyloid found was small for both methods. The median disease duration of the eight amyloid patients was significantly longer (17 years) than that of the non-amyloid patients (10 years). Bronchopulmonary disease and constipation were more common, whereas proteinuria and chronic renal insufficiency were not. The number of swollen joints and the number of red blood cells were significantly lower in the amyloid group. CONCLUSIONS: Quantification of amyloid A protein and staining with Congo red are strongly concordant methods of screening for amyloid in fat tissue. The prevalence of amyloid in Egyptian patients with RA is 7%. Proteinuria is not a discriminating feature, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells may help to identify the arthritic patients with amyloid. PMID- 11779758 TI - Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies. AB - OBJECTIVE: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. METHODS: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, chi(2), Fisher's exact test, and Woolf's method for odds ratio (OR). RESULTS: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). CONCLUSION: In addition to the association of SpA with HLA B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA. PMID- 11779759 TI - Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography. AB - OBJECTIVE: To determine the usefulness of computed tomography (CT), magnetic resonance imaging (MRI), and Doppler ultrasonography (US) in providing specific images of gouty tophi. METHODS: Four male patients with chronic gout with tophi affecting the knee joints (three cases) or the olecranon processes of the elbows (one case) were assessed. Crystallographic analyses of the synovial fluid or tissue aspirates of the areas of interest were made with polarising light microscopy, alizarin red staining, and x ray diffraction. CT was performed with a GE scanner, MR imaging was obtained with a 1.5 T Magneton (Siemens), and ultrasonography with colour Doppler was carried out by standard technique. RESULTS: Crystallographic analyses showed monosodium urate (MSU) crystals in the specimens of the four patients; hydroxyapatite and calcium pyrophosphate dihydrate (CPPD) crystals were not found. A diffuse soft tissue thickening was seen on plain radiographs but no calcifications or ossifications of the tophi. CT disclosed lesions containing round and oval opacities, with a mean density of about 160 Hounsfield units (HU). With MRI, lesions were of low to intermediate signal intensity on T(1) and T(2) weighting. After contrast injection in two cases, enhancement of the tophus was seen in one. Colour Doppler US showed the tophi to be hypoechogenic with peripheral increase of the blood flow in three cases. CONCLUSION: The MR and colour Doppler US images showed the tophi as masses surrounded by a hypervascular area, which cannot be considered as specific for gout. But on CT images, masses of about 160 HU density were clearly seen, which correspond to MSU crystal deposits. PMID- 11779760 TI - High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis receiving treatment with soluble tumour necrosis factor alpha receptor (etanercept). AB - OBJECTIVE: High resolution ultrasound (HRUS) was used to investigate the effects of tumour necrosis factor alpha (TNFalpha) blockade on pannus formation and vascularisation of small finger joints in patients with active rheumatoid arthritis (RA). METHODS: Five patients with active RA were treated with etanercept, a soluble TNFalpha receptor protein, for one month. Before, during, and after treatment the patients were followed up by clinical rheumatological examination, determination of their subjective pain score, blood chemistry, and by HRUS of the second metacarpophalangeal (MCP) joint of the right hand. RESULTS: One month after treatment with etanercept, rheumatological examination showed a significant decrease in a modified single joint rheumatic disease activity index (from 2.9 (SD 0.2) to 1.2 (0.7); p<0.05) in all patients. Moreover, a significant decrease in the general pain score (from 4.7 (0.4) to 1.8 (0.6); p<0.05) and in C reactive protein (CRP) levels was seen (from 3.02 (0.9) to 0.24 (0.1); p<0.05). Concordantly, HRUS showed a significant reduction in pannus vascularisation of the MCPII joints (from 23,602 (5339) to 2907 (1609) colour signals/region of interest, CS/ROI; p<0.001). Pearson's correlation coefficient between the results obtained by HRUS and the clinical response was 0.85. CONCLUSION: HRUS is promising as an additional useful method in the assessment of RA activity, and probably also in monitoring therapeutic responses. PMID- 11779761 TI - Intravenous immunoglobulins control scleromyxoedema. AB - BACKGROUND: Scleromyxoedema is a variant of papular mucinosis affecting the skin and internal organs. The different therapeutic approaches proposed for scleromyxoedema are still unsatisfactory. Intravenous immunoglobulin (IVIg) has been successfully employed in the treatment of connective tissue diseases and vasculitides. PATIENTS: The successful treatment of three cases of scleromyxoedema with IVIg is reported here. CONCLUSIONS: The relatively low risk of the drug and the high effectiveness seen in three patients suggest that IVIg is a new treatment potentially useful in scleromyxoedema. PMID- 11779762 TI - Communication between Dutch rheumatologists and occupational physicians in the occupational rehabilitation of patients with rheumatic diseases. AB - BACKGROUND: Rheumatic diseases are a major cause of permanent work disability. In the process of occupational rehabilitation several health professionals may have a role. OBJECTIVE: To assess the quality and quantity of communication and cooperation between Dutch rheumatologists and occupational physicians. METHODS: A postal survey among 187 Dutch rheumatologists. RESULTS: 153/187 rheumatologists (82%) returned the questionnaire. They considered reducing pain and fatigue to be their major responsibility in the process of occupational rehabilitation, followed by improving work participation (68/153 (44%)) and quality of work (55/153 (36%)). Although 112/153 (73%) of the rheumatologists judged the communication and cooperation with occupational physicians as reasonable to good, 119/153 (78%) of them were willing to improve the collaboration. Perceived bottlenecks mentioned were a lack of clarity about the occupational physician's position and activities, and the absence of practice guidelines. The most important prerequisites for improvement were found to be guarantees about the occupational physician's professional independence and more clarity about the competence of the occupational physicians and how they used the information provided. CONCLUSION: Dutch rheumatologists are willing to improve cooperation and communication with occupational physicians. The perceived lack of clarity about their mutual tasks appears to be a major obstacle. Thus the development of a joint education programme and a guideline for occupational rehabilitation in rheumatic diseases may be appropriate first steps towards improvement. PMID- 11779763 TI - Can intervention modify adverse lifestyle variables in a rheumatoid population? Results of a pilot study. AB - BACKGROUND: Rheumatoid arthritis (RA) is associated with significant excess morbidity and mortality. Cardiovascular disease is the commonest cause of premature death in patients with RA. In recognition of this, blood pressure, weight, and smoking history are routinely ascertained in the clinic and appropriate advice and treatment started. AIMS: To ascertain if attending a specialist nurse, in addition to routine medical care, would increase the success in dealing with lifestyle variables in a cohort of patients with RA. METHODS: Twenty two consecutive patients starting treatment with the disease modifying antirheumatic drug (DMARD) sulfasalazine were invited to attend an additional clinic dealing with lifestyle factors every 12 weeks over a 48 week follow up. Smoking and alcohol history, baseline demographic and metrology assessments were determined for all patients. Body mass index (BMI) was calculated, blood pressure recorded, function assessed by the Health Assessment Questionnaire (HAQ), and social deprivation determined by the Carstairs Index. Patients were advised on exercise and diet, and serum cholesterol was measured. RESULTS: Twenty women and two men, with a mean age of 52 years and mean disease duration of five years, were enrolled. Eight patients smoked and, unfortunately, none were persuaded to discontinue. Fifteen of the cohort were already taking regular exercise; one additional patient began swimming regularly. At baseline, 10 patients were found to have a high cholesterol, with a mean of 6.8 mmol/l. A 14% reduction in mean cholesterol was achieved by dietary modification, and three patients merited statin treatment. Obesity is a major problem in our population and 15 of the patients had grade I obesity with a mean BMI of 30.6; five of these gained a further 4.5 kg. Six patients with previously untreated hypertension were identified, but unfortunately five remained hypertensive and only two had received anti-hypertensive drugs. CONCLUSIONS: Educating patients in order to change lifestyle habits and influence outcome is a long term challenge facing all healthcare workers. In our cohort, most adverse lifestyle factors had already been recognised and discussed by the general practitioner or at prior clinic visits. Additional advice and input led to only modest improvement. PMID- 11779764 TI - Autoimmune thyroid disease in systemic lupus erythematosus. AB - BACKGROUND: The reported prevalence of autoimmune thyroid disease (3.9-24%) and antithyroid antibodies (11-51%) in SLE varies considerably. Early reports were mainly based on short term studies of small cohorts. OBJECTIVE: To report the prevalence of autoimmune thyroid disease and thyroid antibodies in 300 patients with SLE, followed up at our centre between 1978 and 2000, by a retrospective analysis of case notes. RESULTS: The prevalence (5.7%) of hypothyroidism in our cohort was higher than in the normal population (1%), while that of hyperthyroidism (1.7%) was not significantly different. Overall 42/300 (14%) of our cohort had thyroid antibodies, rising to 15/22 (68%) in the subgroup who also had thyroid disease (p<0.001). Both antimicrosomal and antithyroglobulin antibodies were detected. The antibodies were found in equally high frequency in the hyperthyroid subgroup (80% patients), whereas in the hypothyroid subgroup antimicrosomal antibodies were more frequent than antithyroglobulin antibodies (64% v 41%). There was no significant difference in the frequency with which antimicrosomal or antithyroglobulin antibodies were detected between the hyperthyroid and hypothyroid subgroups (p>0.2). CONCLUSION: Our patients with SLE had a prevalence of hypothyroidism, but not hyperthyroidism, greater than that of the normal population. The presence of either condition was associated with a higher frequency of both antimicrosomal and antithyroglobulin antibodies. PMID- 11779765 TI - Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures. AB - OBJECTIVE: To analyse whether bone mineral density (BMD) assessment is required in postmenopausal women presenting with low trauma vertebral fracture. METHODS: Women with vertebral fracture diagnosed over a 10 year period were recruited from our database. The following were excluded: (a) patients with high energy trauma; (b) patients with malignancies; (c) patients with a metabolic bone disease other than osteoporosis. All postmenopausal women were included in whom BMD had been evaluated at both the lumbar spine and femoral neck by dual energy x ray absorptiometry during the six months after the diagnosis. Patients with a potential cause of osteoporosis other than age and menopause were not considered. A total of 215 patients were identified. RESULTS: The mean (SD) age of the patients was 65.9 (6.9) years. BMD at the lumbar spine was 0.725 (0.128) g/cm(2) and the T score was -2.94 (1.22); BMD at the femoral neck was 0.598 (0.095) g/cm(2) and the T score was -2.22 (0.89). The BMD of the patients was significantly lower than that of the general population at both the lumbar spine and femoral neck. When the lowest value of the two analysed zones was considered, six patients (3%) showed a normal BMD, 51 (23.5%) osteopenia, and 158 (73.5%) osteoporosis. The prevalence of osteoporosis at the femoral neck increased with age; it was 25% in patients under 60, 35% in patients aged 60-70, and 60% in patients over 70. CONCLUSION: These results indicate that bone densitometry is not required in postmenopausal women with clinically diagnosed vertebral fractures if it is performed only to confirm the existence of a low BMD. PMID- 11779766 TI - Serum nitrate and nitrite levels in patients with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. AB - OBJECTIVE: To assess and compare serum nitrate and nitrite levels in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: Thirty five patients with RA, 32 patients with AS, and 36 patients with OA were entered into this study. In addition, 30 healthy volunteers acted as a control group. Concentrations of nitrate and nitrite in serum were determined by direct and indirect Griess reactions. C reactive protein and erythrocyte sedimentation rate levels were determined as markers of systemic activity of disease (SAD) in RA and AS groups. RESULTS: Serum nitrate and nitrite levels were found to be higher in patients with AS and RA than in the OA group (p<0.01). In addition, serum nitrate and nitrite levels were higher in all three groups than in the control group (p<0.01). Moreover, serum nitrate and nitrite levels were higher in patients who had SAD than in those who had not in the RA and AS groups (p<0.01 and p<0.05, respectively), and there was a correlation between serum nitrate and nitrite concentrations and SAD variables in patients with RA (Spearman's r(s)=0.414, p<0.05 and r(s)=0.408, p<0.05, respectively) and AS (r(s)=0.421, p<0.05 and r(s)=0.412, p<0.05, respectively). CONCLUSION: The findings suggest that nitrate and nitrite production is enhanced in patients with inflammatory arthritis compared with OA. In addition, serum nitrate and nitrite levels are enhanced in patients with RA, AS, and OA compared with healthy subjects. Furthermore, there is a correlation between the SAD variables and serum nitrate and nitrite levels in patients with RA and AS. PMID- 11779767 TI - Acute phase response in familial Mediterranean fever. AB - OBJECTIVE: To test the hypothesis that not all acute phase reactants respond in the same way during attacks of familial Mediterranean fever (FMF) and that there is a subclinical acute phase response (APR) in a proportion of patients during the interval between attacks. METHODS: Blood and urine samples were obtained from 49 patients with FMF during an attack and the attack-free period that followed, to test for erythrocyte sedimentation rate, C reactive protein (CRP), fibrinogen, white blood cell count, platelet count, factor VIII related antigen, haptoglobin, protein electrophoresis, ferritin, proteinuria, and haematuria. Control groups comprised 29 patients with juvenile idiopathic arthritis, 10 patients with various infectious diseases, and 19 healthy subjects. RESULTS: A marked APR was seen during the FMF attacks which was comparable with that obtained in the diseased control groups. CRP was the only acute phase protein that was raised during all attacks. Neither thrombocytosis nor an increase in ferritin levels (except one) was noted in any attack. Serum albumin levels remained unchanged. In two thirds of the patients with FMF a continuing APR was seen in between the attacks. CONCLUSION: Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period. PMID- 11779768 TI - Rheumatological complications associated with the use of indinavir and other protease inhibitors. AB - Several cases are reported of rheumatological pathology (temporomandibular dysfunction, frozen shoulder, Dupuytren's disease, and tendinitis) most probably related to the intake of indinavir in HIV positive patients. A survey using an anonymous questionnaire of 878 people with HIV infection treated with antiretroviral drugs suggests that other protease inhibitors may also cause arthralgia. PMID- 11779769 TI - Antiphospholipid antibodies and rheumatoid arthritis. PMID- 11779770 TI - Methotrexate and postoperative complications. PMID- 11779771 TI - Proximal myopathy and bone pain as the presenting features of coeliac disease. PMID- 11779772 TI - Essential cryoglobulinaemia (type 1) in three patients characterised by Raynaud's phenomenon, arthralgia-arthritis, and skin lesions. PMID- 11779773 TI - Plasma and peripheral blood mononuclear cells levels of Zn and Cu among Indian patients with RA. PMID- 11779774 TI - Cryoglobulinaemic vasculitis as presenting manifestation of infective endocarditis. PMID- 11779775 TI - ANCA antibodies in Graves' disease. PMID- 11779776 TI - Lupus relapse after prostaglandin E(1) administration: activation of a cytokine cascade? PMID- 11779777 TI - Takayasu arteritis. PMID- 11779778 TI - Osteocalcin: a marker of disease activity in ankylosing spondylitis? PMID- 11779779 TI - Recurrent orbital pain and diplopia in a 12 year old boy. PMID- 11779780 TI - Unusual complications in the Churg-Strauss syndrome. PMID- 11779781 TI - Sciatica or spinal lymphoma. PMID- 11779782 TI - Evolution by jumps: Francis Galton and William Bateson and the mechanism of evolutionary change. PMID- 11779783 TI - Profiles of adaptation in two similar viruses. AB - The related bacteriophages phiX174 and G4 were adapted to the inhibitory temperature of 44 degrees and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of phiX174 improved from -0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5 degrees before it could be maintained at 44 degrees. Its fitness at 44 degrees increased from -2.7 to 3.2, nearly the same net gain as in phiX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation. PMID- 11779784 TI - Growth-dependent DNA breakage and cell death in a gyrase mutant of Salmonella. AB - A class of gyrase mutants of Salmonella enterica mimics the properties of bacteria exposed to quinolones. These mutants suffer spontaneous DNA breakage during normal growth and depend on recombinational repair for viability. Unlike quinolone-treated bacteria, however, they do not show accumulation of cleavable gyrase-DNA complexes. In recA or recB mutant backgrounds, the temperature sensitive (ts) allele gyrA208 causes rapid cell death at 43 degrees. Here, we isolated "suppressor-of-death" mutations, that is, secondary changes that allow a gyrA208 recB double mutant to survive a prolonged exposure to 43 degrees and subsequently to form colonies at 28 degrees. In most isolates, the secondary change was itself a ts mutation. Three ts alleles were mapped in genes coding for amino acyl tRNA synthetases (alaS, glnS, and lysS). Allele alaS216 completely abolished DNA breakage in a gyrA208 recA double mutant. Likewise, treating this mutant with chloramphenicol prevented death and DNA damage at 43 degrees. Additional suppressors of gyrA208 lethality include rpoB mutations and, surprisingly, icd mutations inactivating isocitrate dehydrogenase. We postulate that the primary effect of the gyrase alteration is to hamper replication fork movement. Inhibiting DNA replication under conditions of continuing macromolecular synthesis ("unbalanced growth") activates a mechanism that causes DNA breakage and cell death, reminiscent of "thymineless" lethality. PMID- 11779785 TI - On the mod resc model and the evolution of Wolbachia compatibility types. AB - Cytoplasmic incompatibility (CI) is induced by the endocellular bacterium Wolbachia. It results in an embryonic mortality occurring when infected males mate with uninfected females. The mechanism involved is currently unknown, but the mod resc model allows interpretation of all observations made so far. It postulates the existence of two bacterial functions: modification (mod) and rescue (resc). The mod function acts in the males' germline, before Wolbachia are shed from maturing sperm. If sperm is affected by mod, zygote development will fail unless resc is expressed in the egg. Interestingly, CI is also observed in crosses between infected males and infected females when the two partners bear different Wolbachia strains, demonstrating that mod and resc interact in a specific manner: Two Wolbachia strains are compatible with each other only if they harbor the same compatibility type. Here we focus on the evolutionary process involved in the emergence of new compatibility types from ancestral ones. We argue that new compatibility types are likely to evolve under a wider range of conditions than previously thought, through a two-step process. First, new mod variants can arise by mutation and spread by drift. This is possible because mod is expressed in males and Wolbachia is transmitted by females. Second, once such a mod variant achieves a certain frequency, it can create the conditions for the deterministic invasion of a new resc variant, allowing the invasion of a new mod resc pair. Furthermore, we show that a stable polymorphism might be maintained in natural populations, allowing the long-term existence of "suicidal" Wolbachia strains. PMID- 11779786 TI - Overlapping functions of the Saccharomyces cerevisiae Mre11, Exo1 and Rad27 nucleases in DNA metabolism. AB - MRE11 functions in several aspects of DNA metabolism, including meiotic recombination, double-strand break repair, and telomere maintenance. Although the purified protein exhibits 3' to 5' exonuclease and endonuclease activities in vitro, Mre11 is implicated in the 5' to 3' resection of duplex ends in vivo. The mre11-H125N mutation, which eliminates the nuclease activities of Mre11, causes an accumulation of unprocessed double-strand breaks (DSBs) in meiosis, but no defect in processing HO-induced DSBs in mitotic cells, suggesting the existence of redundant activities. Mutation of EXO1, which encodes a 5' to 3' exonuclease, was found to increase the ionizing radiation sensitivity of both mre11Delta and mre11-H125N strains, but the exo1 mre11-H125N strain showed normal kinetics of mating-type switching and was more radiation resistant than the mre11Delta strain. This suggests that other nucleases can compensate for loss of the Exo1 and Mre11 nucleases, but not of the Mre11-Rad50-Xrs2 complex. Deletion of RAD27, which encodes a flap endonuclease, causes inviability in mre11 strains. When mre11-H125N was combined with the leaky rad27-6, the double mutants were viable and no more gamma-ray sensitive than the mre11-H125N strain. This suggests that the double mutant defect is unlikely to be due to defective DSB processing. PMID- 11779787 TI - Overactivation of the protein kinase C-signaling pathway suppresses the defects of cells lacking the Rho3/Rho4-GAP Rgd1p in Saccharomyces cerevisiae. AB - The nonessential RGD1 gene encodes a Rho-GTPase activating protein for the Rho3 and Rho4 proteins in Saccharomyces cerevisiae. Previous studies have revealed genetic interactions between RGD1 and the SLG1 and MID2 genes, encoding two putative sensors for cell integrity signaling, and VRP1 encoding an actin and myosin interacting protein involved in polarized growth. To better understand the role of Rgd1p, we isolated multicopy suppressor genes of the cell lethality of the double mutant rgd1Delta mid2Delta. RHO1 and RHO2 encoding two small GTPases, MKK1 encoding one of the MAP-kinase kinases in the protein kinase C (PKC) pathway, and MTL1, a MID2-homolog, were shown to suppress the rgd1Delta defects strengthening the functional links between RGD1 and the cell integrity pathway. Study of the transcriptional activity of Rlm1p, which is under the control of Mpk1p, the last kinase of the PKC pathway, and follow-up of the PST1 transcription, which is positively regulated by Rlm1p, indicate that the lack of RGD1 function diminishes the PKC pathway activity. We hypothesize that the rgd1Delta inactivation, at least through the hyperactivation of the small GTPases Rho3p and Rho4p, alters the secretory pathway and/or the actin cytoskeleton and decreases activity of the PKC pathway. PMID- 11779788 TI - Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have conserved roles in genome maintenance. AB - Most Ty1 retrotransposons in the genome of Saccharomyces cerevisiae are transpositionally competent but rarely transpose. We screened yeast mutagenized by insertion of the mTn3-lacZ/LEU2 transposon for mutations that result in elevated Ty1 cDNA-mediated mobility, which occurs by cDNA integration or recombination. Here, we describe the characterization of mTn3 insertions in 21 RTT (regulation of Ty1 transposition) genes that result in 5- to 111-fold increases in Ty1 mobility. These 21 RTT genes are EST2, RRM3, NUT2, RAD57, RRD2, RAD50, SGS1, TEL1, SAE2, MED1, MRE11, SCH9, KAP122, and 8 previously uncharacterized genes. Disruption of RTT genes did not significantly increase Ty1 RNA levels but did enhance Ty1 cDNA levels, suggesting that most RTT gene products act at a step after mRNA accumulation but before cDNA integration. The rtt mutations had widely varying effects on integration of Ty1 at preferred target sites. Mutations in RTT101 and NUT2 dramatically stimulated Ty1 integration upstream of tRNA genes. In contrast, a mutation in RRM3 increased Ty1 mobility >100-fold without increasing integration upstream of tRNA genes. The regulation of Ty1 transposition by components of fundamental pathways required for genome maintenance suggests that Ty1 and yeast have coevolved to link transpositional dormancy to the integrity of the genome. PMID- 11779789 TI - Counteracting regulation of chromatin remodeling at a fission yeast cAMP response element-related recombination hotspot by stress-activated protein kinase, cAMP dependent kinase and meiosis regulators. AB - In fission yeast, an ATF/CREB-family transcription factor Atf1-Pcr1 plays important roles in the activation of early meiotic processes via the stress activated protein kinase (SAPK) and the cAMP-dependent protein kinase (PKA) pathways. In addition, Atf1-Pcr1 binds to a cAMP responsive element (CRE)-like sequence at the site of the ade6-M26 mutation, which results in local enhancement of meiotic recombination and chromatin remodeling. Here we studied the roles of meiosis-inducing signal transduction pathways in M26 chromatin remodeling. Chromatin analysis revealed that persistent activation of PKA in meiosis inhibited M26 chromatin remodeling, suggesting that the PKA pathway represses M26 chromatin remodeling. The SAPK pathway activated M26 chromatin remodeling, since mutants lacking a component of this pathway, the Wis1 or Spc1/Sty1 kinases, had no M26 chromatin remodeling. M26 chromatin remodeling also required the meiosis regulators Mei2 and Mei3 but not the subsequently acting regulators Sme2 and Mei4, suggesting that induction of M26 chromatin remodeling needs meiosis inducing signals before premeiotic DNA replication. Similar meiotic chromatin remodeling occurred meiotically around natural M26 heptamer sequences. These results demonstrate the coordinated action of genetic and physiological factors required to remodel chromatin in preparation for high levels of meiotic recombination and eukaryotic cellular differentiation. PMID- 11779790 TI - Sit4p protein phosphatase is required for sensitivity of Saccharomyces cerevisiae to Kluyveromyces lactis zymocin. AB - We have identified two Saccharomyces cerevisiae genes that, in high copy, confer resistance to Kluyveromyces lactis zymocin, an inhibitor that blocks cells in the G(1) phase of the cell cycle prior to budding and DNA replication. One gene (GRX3) encodes a glutaredoxin and is likely to act at the level of zymocin entry into sensitive cells, while the other encodes Sap155p, one of a family of four related proteins that function positively and interdependently with the Sit4p protein phosphatase. Increased SAP155 dosage protects cells by influencing the sensitivity of the intracellular target and is unique among the four SAP genes in conferring zymocin resistance in high copy, but is antagonized by high-copy SAP185 or SAP190. Since cells lacking SIT4 or deleted for both SAP185 and SAP190 are also zymocin resistant, our data support a model whereby high-copy SAP155 promotes resistance by competition with the endogenous levels of SAP185 and SAP190 expression. Zymocin sensitivity therefore requires a Sap185p/Sap190p dependent function of Sit4p protein phosphatase. Mutations affecting the RNA polymerase II Elongator complex also confer K. lactis zymocin resistance. Since sit4Delta and SAP-deficient strains share in common several other phenotypes associated with Elongator mutants, Elongator function may be a Sit4p-dependent process. PMID- 11779791 TI - Phosphate transport and sensing in Saccharomyces cerevisiae. AB - Cellular metabolism depends on the appropriate concentration of intracellular inorganic phosphate; however, little is known about how phosphate concentrations are sensed. The similarity of Pho84p, a high-affinity phosphate transporter in Saccharomyces cerevisiae, to the glucose sensors Snf3p and Rgt2p has led to the hypothesis that Pho84p is an inorganic phosphate sensor. Furthermore, pho84Delta strains have defects in phosphate signaling; they constitutively express PHO5, a phosphate starvation-inducible gene. We began these studies to determine the role of phosphate transporters in signaling phosphate starvation. Previous experiments demonstrated a defect in phosphate uptake in phosphate-starved pho84Delta cells; however, the pho84Delta strain expresses PHO5 constitutively when grown in phosphate-replete media. We determined that pho84Delta cells have a significant defect in phosphate uptake even when grown in high phosphate media. Overexpression of unrelated phosphate transporters or a glycerophosphoinositol transporter in the pho84Delta strain suppresses the PHO5 constitutive phenotype. These data suggest that PHO84 is not required for sensing phosphate. We further characterized putative phosphate transporters, identifying two new phosphate transporters, PHO90 and PHO91. A synthetic lethal phenotype was observed when five phosphate transporters were inactivated, and the contribution of each transporter to uptake in high phosphate conditions was determined. Finally, a PHO84-dependent compensation response was identified; the abundance of Pho84p at the plasma membrane increases in cells that are defective in other phosphate transporters. PMID- 11779792 TI - Spontaneous chromosome loss in Saccharomyces cerevisiae is suppressed by DNA damage checkpoint functions. AB - Genomic instability is one of the hallmarks of cancer cells and is often the causative factor in revealing recessive gene mutations that progress cells along the pathway to unregulated growth. Genomic instability can take many forms, including aneuploidy and changes in chromosome structure. Chromosome loss, loss and reduplication, and deletions are the majority events that result in loss of heterozygosity (LOH). Defective DNA replication, repair, and recombination can significantly increase the frequency of spontaneous genomic instability. Recently, DNA damage checkpoint functions that operate during the S-phase checkpoint have been shown to suppress spontaneous chromosome rearrangements in haploid yeast strains. To further study the role of DNA damage checkpoint functions in genomic stability, we have determined chromosome loss in DNA damage checkpoint-deficient yeast strains. We have found that the DNA damage checkpoints are essential for preserving the normal chromosome number and act synergistically with homologous recombination functions to ensure that chromosomes are segregated correctly to daughter cells. Failure of either of these processes increases LOH events. However, loss of the G2/M checkpoint does not result in an increase in chromosome loss, suggesting that it is the various S-phase DNA damage checkpoints that suppress chromosome loss. The mec1 checkpoint function mutant, defective in the yeast ATR homolog, results in increased recombination through a process that is distinct from that operative in wild-type cells. PMID- 11779793 TI - A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae. AB - The MMS4 gene of Saccharomyces cerevisiae was originally identified due to its sensitivity to MMS in vegetative cells. Subsequent studies have confirmed a role for MMS4 in DNA metabolism of vegetative cells. In addition, mms4 diploids were observed to sporulate poorly. This work demonstrates that the mms4 sporulation defect is due to triggering of the meiotic recombination checkpoint. Genetic, physical, and cytological analyses suggest that MMS4 functions after the single end invasion step of meiotic recombination. In spo13 diploids, red1, but not mek1, is epistatic to mms4 for sporulation and spore viability, suggesting that MMS4 may be required only when homologs are capable of undergoing synapsis. MMS4 and MUS81 are in the same epistasis group for spore viability, consistent with biochemical data that show that the two proteins function in a complex. In contrast, MMS4 functions independently of MSH5 in the production of viable spores. We propose that MMS4 is required for the processing of specific recombination intermediates during meiosis. PMID- 11779794 TI - Differential regulation of two Ca(2+) influx systems by pheromone signaling in Saccharomyces cerevisiae. AB - The budding yeast Saccharomyces cerevisiae generates calcium signals during the response to mating pheromones that promote survival of unmated cells. A Ca(2+) channel composed of Cch1p and Mid1p was previously shown to be necessary for the production of these calcium signals. However, we find that the Cch1p-Mid1p high affinity Ca(2+) influx system (HACS) contributes very little to signaling or survival after treatment with alpha-factor in rich media. HACS activity was much greater after calcineurin inactivation or inhibition, suggesting the Cch1p-Mid1p Ca(2+) channel is subject to direct or indirect regulation by calcineurin. Instead a distinct low-affinity Ca(2+) influx system (LACS) was stimulated by pheromone signaling in rich medium. LACS activity was insensitive to calcineurin activity, independent of Cch1p and Mid1p, and sufficient to elevate cytosolic free Ca(2+) concentrations ([Ca(2+)]c) in spite of its 16-fold lower affinity for Ca(2+). Overexpression of Ste12p or constitutive activation of this transcription factor in dig1 dig2 double mutants had no effect on LACS activity but stimulated HACS activity when calcineurin was also inactivated. Ste12p activation had no effect on Cch1p or Mid1p abundance, suggesting the involvement of another target of Ste12p in HACS stimulation. LACS activation required treatment with mating pheromone even in dig1 dig2 double mutants and also required FAR1, SPA2, and BNI1, which are necessary for proper cell cycle arrest and polarized morphogenesis. These results show that distinct branches of the pheromone signaling pathway independently regulate HACS and LACS activities, either of which can promote survival during long-term responses. PMID- 11779795 TI - (CA/TG) microsatellite sequences escape the inhibition of recombination by mismatch repair in Saccharomyces cerevisiae. AB - Sequence divergence reduces the frequency of recombination, a process that is dependent on the activity of the mismatch repair system. In the yeast Saccharomyces cerevisiae, repair of mismatches results in gene conversion or restoration, whereas failure to repair mismatches results in postmeiotic segregation (PMS). By examining the conversion and PMS in yeast strains deficient in various MMR genes and heterozygous for large inserts (107 bp) with either a mixed sequence or a 39 (CA/TG) repetitive microsatellite sequence, we demonstrate that: (1) the inhibition of conversion by large inserts depends upon a complex containing both Msh2 and Pms1 proteins; (2) conversion is not inhibited if the single-stranded DNA loop in the heteroduplex is the microsatellite sequence; and (3) large heteroduplex loops with random sequence or repetitive sequence might be repaired by two complexes, containing either Msh2 or Pms1. Our results suggest that inhibition of recombination by heterologous inserts and large loop repair are not processed by the same MMR complexes. We propose that the inhibition of conversion by large inserts is due to recognition by the Msh2/Pms1 complex of mismatches created by intrastrand interactions in the heteroduplex loop. PMID- 11779796 TI - Cdc28 and Ime2 possess redundant functions in promoting entry into premeiotic DNA replication in Saccharomyces cerevisiae. AB - In the budding yeast Saccharomyces cerevisiae initiation and progression through the mitotic cell cycle are determined by the sequential activity of the cyclin dependent kinase Cdc28. The role of this kinase in entry and progression through the meiotic cycle is unclear, since all cdc28 temperature-sensitive alleles are leaky for meiosis. We used a "heat-inducible Degron system" to construct a diploid strain homozygous for a temperature-degradable cdc28-deg allele. We show that this allele is nonleaky, giving no asci at the nonpermissive temperature. We also show, using this allele, that Cdc28 is not required for premeiotic DNA replication and commitment to meiotic recombination. IME2 encodes a meiosis specific hCDK2 homolog that is required for the correct timing of premeiotic DNA replication, nuclear divisions, and asci formation. Moreover, in ime2Delta diploids additional rounds of DNA replication and nuclear divisions are observed. We show that the delayed premeiotic DNA replication observed in ime2Delta diploids depends on a functional Cdc28. Ime2Delta cdc28-4 diploids arrest prior to initiation of premeiotic DNA replication and meiotic recombination. Ectopic overexpression of Clb1 at early meiotic times advances premeiotic DNA replication, meiotic recombination, and nuclear division, but the coupling between these events is lost. The role of Ime2 and Cdc28 in initiating the meiotic pathway is discussed. PMID- 11779797 TI - The N terminus of Saccharomyces cerevisiae Sst2p plays an RGS-domain-independent, Mpt5p-dependent role in recovery from pheromone arrest. AB - The Saccharomyces cerevisiae RGS protein Sst2p is involved in desensitization to pheromone and acts as a GTPase-activating protein for the Galpha subunit Gpa1p. Other results indicate that Sst2p acts through Mpt5p and that this action occurs downstream of Fus3p and through Cln3p/Cdc28p. Our results indicate that the interaction of Sst2p with Mpt5p requires the N-terminal MPI (Mpt5p-interacting) domain of Sst2p and is independent of the C-terminal RGS domain. Overexpression of the MPI domain results in an Mpt5p-dependent increase in recovery from pheromone arrest. Overexpression of either intact Sst2p or the MPI domain leads to partial suppression of a gpa1 growth defect, and this suppression is dependent on Mpt5p, indicating that MPI function occurs downstream of Gpa1p and through Mpt5p. Combination of an mpt5 mutation with the GPA1(G302S) mutation, which uncouples Gpa1p from Sst2p, results in pheromone supersensitivity similar to the sst2 mutant, and promotion of recovery by overexpression of Sst2p is dependent on both Mpt5p and the Gpa1p interaction. These results indicate that Sst2p is a bifunctional protein and that the MPI domain acts through Mpt5p independently of the RGS domain. RGS family members from other fungi contain N-terminal domains with sequence similarity to the Sst2p MPI domain, suggesting that MPI function may be conserved. PMID- 11779798 TI - Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon". AB - Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II. PMID- 11779800 TI - Analysis of a mutant exhibiting conditional sorting to dense core secretory granules in Tetrahymena thermophila. AB - The formation of dense core granules (DCGs) requires both the sorting of granule contents from other secretory proteins and a postsorting maturation process. The Tetrahymena thermophila strain SB281 fails to synthesize DCGs, and previous analysis suggested that the defect lay at or near the sorting step. Because this strain represents one of the very few mutants in this pathway, we have undertaken a more complete study of the phenotype. Genetic epistasis analysis places the defect upstream of those in two other characterized Tetrahymena mutants. Using immunofluorescent detection of granule content proteins, as well as GFP tagging, we describe a novel cytoplasmic compartment to which granule contents can be sorted in growing SB281 cells. Cell fusion experiments indicate that this compartment is not a biosynthetic intermediate in DCG synthesis. Sorting in SB281 is strongly conditional with respect to growth. When cells are starved, the storage compartment is degraded and de novo synthesized granule proteins are rapidly secreted. The mutation in SB281 therefore appears to affect DCG synthesis at the level of both sorting and maturation. PMID- 11779799 TI - The Aspergillus nidulans musN gene encodes a RecQ helicase that interacts with the PI-3K-related kinase UVSB. AB - In Aspergillus nidulans, the uvsB gene encodes a member of the PI-3K-related kinase family of proteins. We have recently shown that UVSB is required for multiple aspects of the DNA damage response. Since the musN227 mutation is capable of partially suppressing defects caused by uvsB mutations, we sought to understand the mechanism underlying the suppression by cloning the musN gene. Here, we report that musN encodes a RecQ helicase with homology to S. pombe rqh1, S. cerevisiae sgs1, and human BLM and WRN. Phenotypic characterization of musN mutant alleles reveals that MUSN participates in the response to a variety of genotoxic agents. The slow growth and genotoxin sensitivity of a musN null mutant can be partially suppressed by a defect in homologous recombination caused by the uvsC114 mutation. In addition, we present evidence suggesting that MUSN may promote recovery from the DNA damage response. We suggest that a block to recovery caused by the musN227 mutation, coupled with the modest accumulation of recombination intermediates, can suppress defects caused by uvsB mutations. Finally, we report that another RecQ helicase, ORQA, performs a function that partially overlaps that of MUSN. PMID- 11779801 TI - In Caenorhabditis elegans, the RNA-binding domains of the cytoplasmic polyadenylation element binding protein FOG-1 are needed to regulate germ cell fates. AB - FOG-1 controls germ cell fates in the nematode Caenorhabditis elegans. Sequence analyses revealed that FOG-1 is a cytoplasmic polyadenylation element binding (CPEB) protein; similar proteins from other species have been shown to bind messenger RNAs and regulate their translation. Our analyses of fog-1 mutations indicate that each of the three RNA-binding domains of FOG-1 is essential for activity. In addition, biochemical tests show that FOG-1 is capable of binding RNA sequences in the 3'-untranslated region of its own message. Finally, genetic assays reveal that fog-1 functions zygotically, that the small fog-1 transcript has no detectable function, and that missense mutations in fog-1 cause a dominant negative phenotype. This last observation suggests that FOG-1 acts in a complex, or as a multimer, to regulate translation. On the basis of these data, we propose that FOG-1 binds RNA to regulate germ cell fates and that it does so by controlling the translation of its targets. One of these targets might be the fog 1 transcript itself. PMID- 11779803 TI - Interactions of the Tribolium Sex combs reduced and proboscipedia orthologs in embryonic labial development. AB - The role of Hox genes in the development of insect gnathal appendages has been examined in three insects: the fruitfly, Drosophila melanogaster; the milkweed bug, Oncopeltus fasciatus; and the red flour beetle, Tribolium castaneum. In each of these organisms, the identity of the labium depends on the homeotic genes Sex combs reduced (Scr) and proboscipedia (pb). Loss of pb function in each of the three insects results in homeotic transformation of the labial appendages to legs. In contrast, loss of Scr function yields a different transformation in each species. Interestingly, mutations in Cephalothorax (Cx), the Tribolium ortholog of Scr, transform the labial appendages to antennae, a result seen in the other insects only when both pb and Scr are removed. We show here that the Tribolium labial appendages also develop as antennae in double mutants. Further, we demonstrate that expression of the Tribolium proboscipedia ortholog maxillopedia (mxp) is greatly reduced or absent in the labium of Cx mutant larvae. Thus, in the wild-type labial segment, Cx function is required (directly or indirectly) for mxp transcription. A similar interaction between Scr and pb during Drosophila embryogenesis has been described recently. Thus, this regulatory paradigm appears to be conserved at least within the Holometabola. PMID- 11779802 TI - P-Element repression in Drosophila melanogaster by variegating clusters of P-lacZ white transgenes. AB - In Drosophila, clusters of P transgenes (P-lac-w) display a variegating phenotype for the w marker. In addition, X-ray-induced rearrangements of chromosomes bearing such clusters may lead to enhancement of the variegated phenotype. Since P-lacZ transgenes in subtelomeric heterochromatin have some P-element repression abilities, we tested whether P-lac-w clusters also have the capacity to repress P element activity in the germline. One cluster (T-1), located on a rearranged chromosome (T2;3) and derived from a line bearing a variegating tandem array of seven P-lac-w elements, partially represses the dysgenic sterility (GD sterility) induced by P elements. This cluster also strongly represses in trans the expression of P-lacZ elements in the germline. This latter suppression shows a maternal effect. Finally, the combination of variegating P-lac-w clusters and a single P-lacZ reporter inserted in subtelomeric heterochromatic sequences at the X chromosome telomere (cytological site 1A) leads to strong repression of dysgenic sterility. These results show that repression of P-induced dysgenic sterility can be elicited in the absence of P elements encoding a polypeptide repressor and that a transgene cluster can repress the expression of a single homologous transgene at a nonallelic position. Implications for models of transposable element silencing are discussed. PMID- 11779804 TI - The gypsy insulator of Drosophila affects chromatin structure in a directional manner. AB - Chromatin insulators are thought to regulate gene expression by establishing higher-order domains of chromatin organization, although the specific mechanisms by which these sequences affect enhancer-promoter interactions are not well understood. Here we show that the gypsy insulator of Drosophila can affect chromatin structure. The insulator itself contains several DNase I hypersensitive sites whose occurrence is dependent on the binding of the Suppressor of Hairy wing [Su(Hw)] protein. The presence of the insulator in the 5' region of the yellow gene increases the accessibility of the DNA to nucleases in the promoter proximal, but not the promoter-distal, region. This increase in accessibility is not due to alterations in the primary chromatin fiber, because the number and position of the nucleosomes appears to be the same in the presence or absence of the insulator. Binding of the Su(Hw) protein to insulator DNA is not sufficient to induce changes in chromatin accessibility, and two domains of this protein, presumed to be involved in interactions with other insulator components, are essential for this effect. The presence of Modifier of mdg4 [Mod(mdg4)] protein, a second component of the gypsy insulator, is required to induce these alterations in chromatin accessibility. The results suggest that the gypsy insulator affects chromatin structure and offer insights into the mechanisms by which insulators affect enhancer-promoter interactions. PMID- 11779805 TI - small bristles is required for the morphogenesis of multiple tissues during Drosophila development. AB - We found that mutations in small bristles (sbr) affect several tissues during the development of the fruit fly. In sbr embryos, neurons have defects in pathfinding and the body wall muscles have defective morphology. As adults, sbr flies have smaller and thinner bristles with a reduced diameter, suggesting a defective cytoskeleton within. The phenotypes we observe are consistent with defects in cell morphogenesis. We identified DmNXF1, the Drosophila homolog of a mRNA export protein that has been characterized in human (NXF1/TAP) and yeast (Mex67p) as the protein encoded by the small bristles locus. Given that a global decrease in mRNA export in these mutants is likely, the phenotypes we observe suggest that certain tissues are acutely sensitive to lower levels of cytoplasmic mRNA and the resultant decrease in protein synthesis during key stages of cellular morphogenesis. PMID- 11779806 TI - Inferring population history from microsatellite and enzyme data in serially introduced cane toads, Bufo marinus. AB - Much progress has been made on inferring population history from molecular data. However, complex demographic scenarios have been considered rarely or have proved intractable. The serial introduction of the South-Central American cane toad Bufo marinus in various Caribbean and Pacific islands involves four major phases: a possible genetic admixture during the first introduction, a bottleneck associated with founding, a transitory population boom, and finally, a demographic stabilization. A large amount of historical and demographic information is available for those introductions and can be combined profitably with molecular data. We used a Bayesian approach to combine this information with microsatellite (10 loci) and enzyme (22 loci) data and used a rejection algorithm to simultaneously estimate the demographic parameters describing the four major phases of the introduction history. The general historical trends supported by microsatellites and enzymes were similar. However, there was a stronger support for a larger bottleneck at introductions for microsatellites than enzymes and for a more balanced genetic admixture for enzymes than for microsatellites. Very little information was obtained from either marker about the transitory population boom observed after each introduction. Possible explanations for differences in resolution of demographic events and discrepancies between results obtained with microsatellites and enzymes were explored. Limits of our model and method for the analysis of nonequilibrium populations were discussed. PMID- 11779808 TI - A genetic map in the Mimulus guttatus species complex reveals transmission ratio distortion due to heterospecific interactions. AB - As part of a study of the genetics of floral adaptation and speciation in the Mimulus guttatus species complex, we constructed a genetic linkage map of an interspecific cross between M. guttatus and M. nasutus. We genotyped an F(2) mapping population (N = 526) at 255 AFLP, microsatellite, and gene-based markers and derived a framework map through repeated rounds of ordering and marker elimination. The final framework map consists of 174 marker loci on 14 linkage groups with a total map length of 1780 cM Kosambi. Genome length estimates (2011 2096 cM) indicate that this map provides thorough coverage of the hybrid genome, an important consideration for QTL mapping. Nearly half of the markers in the full data set (49%) and on the framework map (48%) exhibited significant transmission ratio distortion (alpha = 0.05). We localized a minimum of 11 transmission ratio distorting loci (TRDLs) throughout the genome, 9 of which generate an excess of M. guttatus alleles and a deficit of M. nasutus alleles. This pattern indicates that the transmission ratio distortion results from particular interactions between the heterospecific genomes and suggests that substantial genetic divergence has occurred between these Mimulus species. We discuss possible causes of the unequal representation of parental genomes in the F(2) generation. PMID- 11779807 TI - Molecular characterization of Pax6(2Neu) through Pax6(10Neu): an extension of the Pax6 allelic series and the identification of two possible hypomorph alleles in the mouse Mus musculus. AB - Phenotype-based mutagenesis experiments will increase the mouse mutant resource, generating mutations at previously unmarked loci as well as extending the allelic series at known loci. Mapping, molecular characterization, and phenotypic analysis of nine independent Pax6 mutations of the mouse recovered in mutagenesis experiments is presented. Seven mutations result in premature termination of translation and all express phenotypes characteristic of null alleles, suggesting that Pax6 function requires all domains to be intact. Of major interest is the identification of two possible hypomorph mutations: Heterozygotes express less severe phenotypes and homozygotes develop rudimentary eyes and nasal processes and survive up to 36 hr after birth. Pax6(4Neu) results in an amino acid substitution within the third helix of the homeodomain. Three-dimensional modeling indicates that the amino acid substitution interrupts the homeodomain recognition alpha-helix, which is critical for DNA binding. Whereas cooperative dimer binding of the mutant homeodomain to a paired-class DNA target sequence was eliminated, weak monomer binding was observed. Thus, a residual function of the mutated homeodomain may explain the hypomorphic nature of the Pax6(4Neu) allele. Pax6(7Neu) is a base pair substitution in the Kozak sequence and results in a reduced level of Pax6 translation product. The Pax6(4Neu) and Pax6(7Neu) alleles may be very useful for gene-dosage studies. PMID- 11779809 TI - Negative crossover interference in maize translocation heterozygotes. AB - Negative interference describes a situation where two genetic regions have more double crossovers than would be expected considering the crossover rate of each region. We detected negative crossover interference while attempting to genetically map translocation breakpoints in maize. In an attempt to find precedent examples we determined there was negative interference among previously published translocation breakpoint mapping data in maize. It appears that negative interference was greater when the combined map length of the adjacent regions was smaller. Even positive interference appears to have been reduced when the combined lengths of adjacent regions were below 40 cM. Both phenomena can be explained by a reduction in crossovers near the breakpoints or, more specifically, by a failure of regions near breakpoints to become competent for crossovers. A mathematical explanation is provided. PMID- 11779810 TI - Gene conversion within regulatory sequences generates maize r alleles with altered gene expression. AB - The maize r locus encodes a transcription factor that regulates the developmental expression of the plant pigment anthocyanin. In an unusual example of gene regulatory diversity, the R-sc (Sc, strong seed color) and the R-p (P, plant color) alleles of r have nonoverlapping tissue specificity and nonhomologous 5' flanking sequences. Heterozygotes between wild-type P and Sc mutants with Ds6 transposable element inserts (r-sc:m::Ds6 or sc:m) produce colored seed derivatives (Sc+) during meiotic recombination. The sc:m alleles with Ds6 insertion in 3' regions of r produce crossover Sc+ derivatives. sc:m alleles with Ds6 elements inserted in 5' regions produce rare Sc+ derivatives borne on nonrecombinant chromosomes. Among 52 such noncrossover Sc+ derivatives, 18 are indistinguishable from the Sc progenitor in phenotype and DNA sequence [Scp(+) alleles]. The remaining 34 derivatives have strong Sc+ expression, including darkly pigmented aleurone, scutellum, coleoptile, and scutellar node [Scp(e) alleles]. The coleoptile and scutellar node phenotypes are unique from either progenitor but are similar to those of some naturally occurring r alleles. Both classes of Sc+ derivatives are explained by gene conversion between the promoter region of Sc:124 and a homologous region located proximal to P. The recombinational intermediate formed between sc:m alleles and P results in deletion of the Ds6 element alone or both Ds6 and a nearby unrelated transposable element-like sequence. PMID- 11779811 TI - Mutations that reduce sinapoylmalate accumulation in Arabidopsis thaliana define loci with diverse roles in phenylpropanoid metabolism. AB - The products of phenylpropanoid metabolism in Arabidopsis include the three fluorescent sinapate esters sinapoylglucose, sinapoylmalate, and sinapoylcholine. The sinapoylmalate that accumulates in cotyledons and leaves causes these organs to appear blue-green under ultraviolet (UV) illumination. To find novel genes acting in phenylpropanoid metabolism, Arabidopsis seedlings were screened under UV for altered fluorescence phenotypes caused by changes in sinapoylmalate content. This screen identified recessive mutations at four Reduced Epidermal Fluorescence (REF) loci that reduced leaf sinapoylmalate content. Further analyses showed that the ref mutations affected other aspects of phenylpropanoid metabolism and some led to perturbations in normal plant development. A second class of mutations at the Bright Trichomes 1 (BRT1) locus leads to modest reductions in sinapate ester content; however, the most notable phenotype of brt1 mutants is the development of hyperfluorescent trichomes that appear to contain elevated levels of sinapate esters when compared to the wild type. These results indicate that at least five new loci affecting the developmentally regulated accumulation of phenylpropanoid secondary metabolites in Arabidopsis, and the cell specificity of their distribution, have been identified by screening for altered UV fluorescence phenotypes. PMID- 11779812 TI - Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana. AB - The purpose of this project was to identify large numbers of Arabidopsis genes with essential functions during seed development. More than 120,000 T-DNA insertion lines were generated following Agrobacterium-mediated transformation. Transgenic plants were screened for defective seeds and putative mutants were subjected to detailed analysis in subsequent generations. Plasmid rescue and TAIL PCR were used to recover plant sequences flanking insertion sites in tagged mutants. More than 4200 mutants with a wide range of seed phenotypes were identified. Over 1700 of these mutants were analyzed in detail. The 350 tagged embryo-defective (emb) mutants identified to date represent a significant advance toward saturation mutagenesis of EMB genes in Arabidopsis. Plant sequences adjacent to T-DNA borders in mutants with confirmed insertion sites were used to map genome locations and establish tentative identities for 167 EMB genes with diverse biological functions. The frequency of duplicate mutant alleles recovered is consistent with a relatively small number of essential (EMB) genes with nonredundant functions during seed development. Other functions critical to seed development in Arabidopsis may be protected from deleterious mutations by extensive genome duplications. PMID- 11779813 TI - Arabidopsis genes essential for seedling viability: isolation of insertional mutants and molecular cloning. AB - We have undertaken a large-scale genetic screen to identify genes with a seedling lethal mutant phenotype. From screening approximately 38,000 insertional mutant lines, we identified >500 seedling-lethal mutants, completed cosegregation analysis of the insertion and the lethal phenotype for >200 mutants, molecularly characterized 54 mutants, and provided a detailed description for 22 of them. Most of the seedling-lethal mutants seem to affect chloroplast function because they display altered pigmentation and affect genes encoding proteins predicted to have chloroplast localization. Although a high level of functional redundancy in Arabidopsis might be expected because 65% of genes are members of gene families, we found that 41% of the essential genes found in this study are members of Arabidopsis gene families. In addition, we isolated several interesting classes of mutants and genes. We found three mutants in the recently discovered nonmevalonate isoprenoid biosynthetic pathway and mutants disrupting genes similar to Tic40 and tatC, which are likely to be involved in chloroplast protein translocation. Finally, we directly compared T-DNA and Ac/Ds transposon mutagenesis methods in Arabidopsis on a genome scale. In each population, we found only about one-third of the insertion mutations cosegregated with a mutant phenotype. PMID- 11779814 TI - Directional selection and the site-frequency spectrum. AB - In this article we explore statistical properties of the maximum-likelihood estimates (MLEs) of the selection and mutation parameters in a Poisson random field population genetics model of directional selection at DNA sites. We derive the asymptotic variances and covariance of the MLEs and explore the power of the likelihood ratio tests (LRT) of neutrality for varying levels of mutation and selection as well as the robustness of the LRT to deviations from the assumption of free recombination among sites. We also discuss the coverage of confidence intervals on the basis of two standard-likelihood methods. We find that the LRT has high power to detect deviations from neutrality and that the maximum likelihood estimation performs very well when the ancestral states of all mutations in the sample are known. When the ancestral states are not known, the test has high power to detect deviations from neutrality for negative selection but not for positive selection. We also find that the LRT is not robust to deviations from the assumption of independence among sites. PMID- 11779815 TI - The probability of preservation of a newly arisen gene duplicate. AB - Newly emerging data from genome sequencing projects suggest that gene duplication, often accompanied by genetic map changes, is a common and ongoing feature of all genomes. This raises the possibility that differential expansion/contraction of various genomic sequences may be just as important a mechanism of phenotypic evolution as changes at the nucleotide level. However, the population-genetic mechanisms responsible for the success vs. failure of newly arisen gene duplicates are poorly understood. We examine the influence of various aspects of gene structure, mutation rates, degree of linkage, and population size (N) on the joint fate of a newly arisen duplicate gene and its ancestral locus. Unless there is active selection against duplicate genes, the probability of permanent establishment of such genes is usually no less than 1/(4N) (half of the neutral expectation), and it can be orders of magnitude greater if neofunctionalizing mutations are common. The probability of a map change (reassignment of a key function of an ancestral locus to a new chromosomal location) induced by a newly arisen duplicate is also generally >1/(4N) for unlinked duplicates, suggesting that recurrent gene duplication and alternative silencing may be a common mechanism for generating microchromosomal rearrangements responsible for postreproductive isolating barriers among species. Relative to subfunctionalization, neofunctionalization is expected to become a progressively more important mechanism of duplicate-gene preservation in populations with increasing size. However, even in large populations, the probability of neofunctionalization scales only with the square of the selective advantage. Tight linkage also influences the probability of duplicate-gene preservation, increasing the probability of subfunctionalization but decreasing the probability of neofunctionalization. PMID- 11779816 TI - Two-locus sampling distributions and their application. AB - Methods of estimating two-locus sample probabilities under a neutral model are extended in several ways. Estimation of sample probabilities is described when the ancestral or derived status of each allele is specified. In addition, probabilities for two-locus diploid samples are provided. A method for using these two-locus probabilities to test whether an observed level of linkage disequilibrium is unusually large or small is described. In addition, properties of a maximum-likelihood estimator of the recombination parameter based on independent linked pairs of sites are obtained. A composite-likelihood estimator, for more than two linked sites, is also examined and found to work as well, or better, than other available ad hoc estimators. Linkage disequilibrium in the Xq28 and Xq25 region of humans is analyzed in a sample of Europeans (CEPH). The estimated recombination parameter is about five times smaller than one would expect under an equilibrium neutral model. PMID- 11779817 TI - Interval mapping of quantitative trait loci in autotetraploid species. AB - This article presents a method for QTL interval mapping in autotetraploid species for a full-sib family derived by crossing two parents. For each offspring, the marker information on each chromosome is used to identify possible configurations of chromosomes inherited from the two parents and the locations of crossovers on these chromosomes. A branch and bound algorithm is used to identify configurations with the minimum number of crossovers. From these configurations, the conditional probability of each possible QTL genotype for a series of positions along the chromosome can be estimated. An iterative weighted regression is then used to relate the trait values to the QTL genotype probabilities. A simulation study is performed to assess this approach and to investigate the effects of the proportion of codominant to dominant markers, the heritability, and the population size. We conclude that the method successfully locates QTL and estimates their parameters accurately, and we discuss different modes of action of the QTL that may be modeled. PMID- 11779818 TI - Recombination, balancing selection and phylogenies in MHC and self incompatibility genes. AB - Using a coalescent model of multiallelic balancing selection with recombination, the genealogical process as a function of recombinational distance from a site under selection is investigated. We find that the shape of the phylogenetic tree is independent of the distance to the site under selection. Only the timescale changes from the value predicted by Takahata's allelic genealogy at the site under selection, converging with increasing recombination to the timescale of the neutral coalescent. However, if nucleotide sequences are simulated over a recombining region containing a site under balancing selection, a phylogenetic tree constructed while ignoring such recombination is strongly affected. This is true even for small rates of recombination. Published studies of multiallelic balancing selection, i.e., the major histocompatibility complex (MHC) of vertebrates, gametophytic and sporophytic self-incompatibility of plants, and incompatibility of fungi, all observe allelic genealogies with unexpected shapes. We conclude that small absolute levels of recombination are compatible with these observed distortions of the shape of the allelic genealogy, suggesting a possible cause of these observations. Furthermore, we illustrate that the variance in the coalescent with recombination process makes it difficult to locate sites under selection and to estimate the selection coefficient from levels of variability. PMID- 11779819 TI - Heterosis, marker mutational processes and population inbreeding history. AB - Genotype-fitness correlations (GFC) have previously been studied using allozyme markers and have often focused on short-term processes such as recent inbreeding. Thus, models of GFC usually neglect marker mutation and only use heterozygosity as a genotypic index. Recently, GFC have also been reported (i) with DNA markers such as microsatellites, characterized by high mutation rates and specific mutational processes and (ii) using new individual genotypic indices assumed to be more precise than heterozygosity. The aim of this article is to evaluate the theoretical impact of marker mutation on GFC. We model GFC due to short-term processes generated by the current breeding system (partial selfing) and to long term processes generated by past population history (hybridization). Various mutation rates and mutation models corresponding to different kinds of molecular markers are considered. Heterozygosity is compared to other genotypic indices designed for specific marker types. Highly mutable markers (such as microsatellites) are particularly suitable for the detection of GFC that evolve in relation to short-term processes, whereas GFC due to long-term processes are best observed with intermediate mutation rates. Irrespective of the marker type and population scenario, heterozygosity usually provides higher correlations than other genotypic indices under most biologically plausible conditions. PMID- 11779820 TI - Meiotic alterations in CAG repeat tracts. AB - We have investigated meiotic changes in CAG repeat tracts embedded in a yeast chromosome. Repeat tracts undergo either conversion events between homologs or expansion and contraction events that appear to be confined to a single chromatid. We did not find evidence for conversion of tract interruptions or excess exchange of flanking markers. PMID- 11779825 TI - Testing the parsimony test of genome duplications: a counterexample. PMID- 11779827 TI - Genomes in flux: the evolution of archaeal and proteobacterial gene content. AB - In the course of evolution, genomes are shaped by processes like gene loss, gene duplication, horizontal gene transfer, and gene genesis (the de novo origin of genes). Here we reconstruct the gene content of ancestral Archaea and Proteobacteria and quantify the processes connecting them to their present day representatives based on the distribution of genes in completely sequenced genomes. We estimate that the ancestor of the Proteobacteria contained around 2500 genes, and the ancestor of the Archaea around 2050 genes. Although it is necessary to invoke horizontal gene transfer to explain the content of present day genomes, gene loss, gene genesis, and simple vertical inheritance are quantitatively the most dominant processes in shaping the genome. Together they result in a turnover of gene content such that even the lineage leading from the ancestor of the Proteobacteria to the relatively large genome of Escherichia coli has lost at least 950 genes. Gene loss, unlike the other processes, correlates fairly well with time. This clock-like behavior suggests that gene loss is under negative selection, while the processes that add genes are under positive selection. PMID- 11779828 TI - Genome-scale evolution: reconstructing gene orders in the ancestral species. AB - Recent progress in genome-scale sequencing and comparative mapping raises new challenges in studies of genome rearrangements. Although the pairwise genome rearrangement problem is well-studied, algorithms for reconstructing rearrangement scenarios for multiple species are in great need. The previous approaches to multiple genome rearrangement problem were largely based on the breakpoint distance rather than on a more biologically accurate rearrangement (reversal) distance. Another shortcoming of the existing software tools is their inability to analyze rearrangements (inversions, translocations, fusions, and fissions) of multichromosomal genomes. This paper proposes a new multiple genome rearrangement algorithm that is based on the rearrangement (rather than breakpoint) distance and that is applicable to both unichromosomal and multichromosomal genomes. We further apply this algorithm for genome-scale phylogenetic tree reconstruction and deriving ancestral gene orders. In particular, our analysis suggests a new improved rearrangement scenario for a very difficult Campanulaceae cpDNA dataset and a putative rearrangement scenario for human, mouse and cat genomes. PMID- 11779826 TI - Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome. AB - Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a approximately 1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (approximately 300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of approximately 3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder. PMID- 11779829 TI - Relating whole-genome expression data with protein-protein interactions. AB - We investigate the relationship of protein-protein interactions with mRNA expression levels, by integrating a variety of data sources for yeast. We focus on known protein complexes that have clearly defined interactions between their subunits. We find that subunits of the same protein complex show significant coexpression, both in terms of similarities of absolute mRNA levels and expression profiles, e.g., we can often see subunits of a complex having correlated patterns of expression over a time course. We classify the yeast protein complexes as either permanent or transient, with permanent ones being maintained through most cellular conditions. We find that, generally, permanent complexes, such as the ribosome and proteasome, have a particularly strong relationship with expression, while transient ones do not. However, we note that several transient complexes, such as the RNA polymerase II holoenzyme and the replication complex, can be subdivided into smaller permanent ones, which do have a strong relationship to gene expression. We also investigated the interactions in aggregated, genome-wide data sets, such as the comprehensive yeast two-hybrid experiments, and found them to have only a weak relationship with gene expression, similar to that of transient complexes. (Further details on genecensus.org/expression/interactions and bioinfo.mbb.yale.edu/expression/interactions.) PMID- 11779830 TI - Systematic identification of novel protein domain families associated with nuclear functions. AB - A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic lineages, but 3 are species specific. For about 500 of the 1200 proteins that contain these new domains, nuclear localization could be inferred, and for 700, additional features could be predicted. For example, we identified a new domain, likely to have a role downstream of the unfolded protein response; a nematode specific signalling domain; and a widespread domain, likely to be a noncatalytic homolog of ubiquitin-conjugating enzymes. PMID- 11779831 TI - A comparative genomic analysis of two distant diptera, the fruit fly, Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae. AB - Genome evolution entails changes in the DNA sequence of genes and intergenic regions, changes in gene numbers, and also changes in gene order along the chromosomes. Genes are reshuffled by chromosomal rearrangements such as deletions/insertions, inversions, translocations, and transpositions. Here we report a comparative study of genome organization in the main African malaria vector, Anopheles gambiae, relative to the recently determined sequence of the Drosophila melanogaster genome. The ancestral lines of these two dipteran insects are thought to have separated approximately 250 Myr, a long period that makes this genome comparison especially interesting. Sequence comparisons have identified 113 pairs of putative orthologs of the two species. Chromosomal mapping of orthologous genes reveals that each polytene chromosome arm has a homolog in the other species. Between 41% and 73% of the known orthologous genes remain linked in the respective homologous chromosomal arms, with the remainder translocated to various nonhomologous arms. Within homologous arms, gene order is extensively reshuffled, but a limited degree of conserved local synteny (microsynteny) can be recognized. PMID- 11779832 TI - Human paralogs of KIAA0187 were created through independent pericentromeric directed and chromosome-specific duplication mechanisms. AB - KIAA0187 is a gene of unknown function that maps to 10q11 and has been subject to recent duplication events. Here we analyze 18 human paralogs of this gene and show that paralogs of exons 14-23 were formed through satellite-associated pericentromeric-directed duplication, whereas paralogs of exons 1-9 were created via chromosome-specific satellite-independent duplications. In silico, Northern, and RT-PCR analyses indicate that nine paralogs are transcribed, including four in which KIAA0187 exons are spliced onto novel sequences. Despite this, no new genes appear to have been created by these events. The chromosome 10 paralogs map to 10q11, 10q22, 10q23.1, and 10q23.3, forming part of a complex family of chromosome-specific repeats that includes GLUD1, Cathepsin L, and KIAA1099 pseudogenes. Phylogenetic analyses and comparative FISH indicates that the 10q23.1 and 10q23.3 repeats were created in 10q11 and relocated by a paracentric inversion 13 to 27 Myr ago. Furthermore, the most recent duplications, involving the KIAA1099 pseudogenes, have largely been confined to 10q11. These results indicate a simple model for the evolution of this repeat family, involving multiple rounds of centromere-proximal duplication and dispersal through intrachromosomal rearrangement. However, more complex events must be invoked to account for high sequence identity between some paralogs. PMID- 11779833 TI - Genomic analysis of the olfactory receptor region of the mouse and human T-cell receptor alpha/delta loci. AB - We have conducted a comparative genomic analysis of several olfactory receptor (OR) genes that lie immediately 5' to the V-alpha gene segments at the mouse and human T-cell receptor (TCR) alpha/delta loci. Five OR genes are identified in the human cluster. The murine cluster has at least six OR genes; the first five are orthologous to the human genes. The sixth mouse gene has arisen since mouse-human divergence by a duplication of a approximately 10-kb block. One pair of OR paralogs found at the mouse and human loci are more similar to each other than to their corresponding orthologs. This paralogous "twinning" appears to be under selection, perhaps to increase sensitivity to particular odorants or to resolve structurally-similar odorants. The promoter regions of the mouse OR genes were identified by RACE-PCR. Orthologs share extensive 5' UTR homology, but we find no significant similarity among paralogs. These findings extend previous observations that suggest that OR genes do not share local significant regulatory homology despite having a common regulatory agenda. We also identified a diverged TCR-alpha gene segment that uses a divergent recombination signal sequence (RSS) to initiate recombination in T-cells from within the OR region. We explored the hypothesis that OR genes may use DNA recombination in expressing neurons, e.g., to recombine ORs into a transcriptionally active locus. We searched the mouse sequence for OR-flanking RSS motifs, but did not find evidence to suggest that these OR genes use TCR-like recombination target sequences. PMID- 11779835 TI - Changes in gene expression profiles in developing B cells of murine bone marrow. AB - Gene expression profiles of five consecutive stages of mouse B cell development were generated with high-density oligonucleotide arrays from as few as 2 x 10(4) ex vivo isolated and flow-cytometrically purified cells. Between 2.8% and 6.8% of all genes change on differentiation from one cellular stage to the next by at least twofold. The entire pathway involves differential expression of 10.7% of all genes. Previously known expression patterns of 15 genes (like surrogate light chain, RAG-1/2, MHC class II, mel-14 antigen) are confirmed. The gene expression patterns of the proliferating pre-BI and large pre-BII cells on the one hand, and the resting immature and mature B cells on the other hand, are most similar to each other. Small pre-BII cells display a pattern that is transitional between these two groups. Most of the genes expressed in early precursors are involved in general processes, like protein folding or cell cycle regulation, whereas more mature precursors express genes involved in more specific molecular programs (cell surface receptors, secreted factors, and adhesion molecules, among others). Between 19 and 139 genes share a given expression pattern. Combining knowledge about gene function and expression pattern allows identification of novel candidate genes potentially involved in self-maintenance of pre-BI cells, allelic exclusion and pre-B cell receptor signaling in large pre BII cells, cell-cycle arrest of small pre-BII cells, propensity toward apoptosis or anergization in immature B cells, propensity toward cell division and activation in mature B cells, and stage-specific interactions with stromal cells in the bone marrow. PMID- 11779836 TI - Expression profiles of 290 ESTs mapped to chromosome 3 in human epithelial ovarian cancer cell lines using DNA expression oligonucleotide microarrays. AB - We have investigated previously the utility of oligonucleotide expression microarray technology in an analysis of four spontaneously transformed epithelial ovarian cancer (EOC) cell lines, TOV-21G, TOV-81D, OV-90, and TOV-112D. Here, we examine the expression of 290 expressed sequence tags (ESTs) that map to human chromosome 3 in a primary culture derived from normal ovarian surface epithelium (NOSE), NOV-31, and the four spontaneously transformed EOC cell lines. One of these cell lines, OV-90, harbors a deletion of an entire chromosome 3p arm. Whereas the most aggressive cell lines (OV-90, TOV-112D, and TOV-21G) exhibited the highest levels of expression, assessed by the mean of expression values of all ESTs, OV-90 showed the lowest mean of expression of ESTs that map to the 3p arm in comparison with TOV-112D and TOV-21G. This difference in expression profile of 3p ESTs in OV-90 is also reflected in the ratio of expression of ESTs on 3p versus the 3q arm and in that the expression values of ESTs that map to 3p were more often lower than higher in OV-90 in two-way comparisons with NOV-31, TOV-21G, and TOV-112D. The loss of a 3p arm does not affect the pattern of differential expression in analyses based on the range of numeric expression values of each EST or fold differences in expression for each EST in comparison with NOV-31. However, 25 differentially expressed ESTs were identified on the basis of threefold differences in expression values between NOV-31 and any EOC cell line; and six of these ESTs were differentially expressed uniquely in OV-90. The investigation of these ESTs could facilitate the identification of novel chromosome 3 genes implicated in ovarian tumorigenesis. PMID- 11779834 TI - Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia. AB - Min (Multiple intestinal neoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al 1992). Polyp multiplicity in Min mice is greatly influenced by genetic background. A modifier locus, Mom1 (Modifier of Min 1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multiplicity. Mom1 is a semidominant modifier of polyp size and multiplicity in Min mice (Gould and Dove 1997), and encodes the secretory type II nonpancreatic phospholipase A2 (Pla2g2a) gene (MacPhee et al. 1995; Cornier et al. 1997, 2000). We now report the identification of a second Modifier of Min 2 (Mom2) locus that is the result of a spontaneous mutation. One resistant Mom2 allele can suppress 88%-95% of polyps detected in Apc(Min)/+ mice, indicating that Mom2 acts in a dominant fashion. Linkage analysis has localized Mom2 to distal mouse chromosome 18. The effects of the Mom2 locus on reducing polyp multiplicity are stronger than the effects of the Mom1 locus, in both the small and large intestines. Some Apc(Min)/+ mice that carried one resistant Mom2 allele were tumor-free at 21 weeks of age, even in the absence of a resistant Mom1 allele. Thus, the resistant Mom2 allele can, in some cases, completely suppress the penetrance of the Apc(Min) mutation. PMID- 11779837 TI - Athila4 of Arabidopsis and Calypso of soybean define a lineage of endogenous plant retroviruses. AB - The Athila retroelements of Arabidopsis thaliana encode a putative envelope gene, suggesting that they are infectious retroviruses. Because most insertions are highly degenerate, we undertook a comprehensive analysis of the A. thaliana genome sequence to discern their conserved features. One family (Athila4) was identified whose members are largely intact and share >94% nucleotide identity. As a basis for comparison, related elements (the Calypso elements) were characterized from soybean. Consensus Calypso and Athila4 elements are 12-14 kb in length and have long terminal repeats of 1.3-1.8 kb. Gag and Pol are encoded on a single open reading frame (ORF) of 1801 (Calypso) and 1911 (Athila4) amino acids. Following the Gag-Pol ORF are noncoding regions of ~0.7 and 2 kb, which, respectively, flank the env-like gene. The env-like ORF begins with a putative splice acceptor site and encodes a protein with a predicted central transmembrane domain, similar to retroviral env genes. RNA of Athila elements was detected in an A. thaliana strain with decreased DNA methylation (ddm1). Additionally, a PCR survey identified related reverse transcriptases in diverse angiosperm genomes. Their ubiquitous nature and the potential for horizontal transfer by infection implicates these endogenous retroviruses as important vehicles for plant genome evolution. PMID- 11779839 TI - Gene expression analysis with universal n-mer arrays. AB - Gene expression profiling is one of the many applications that have benefited from the massively parallel nucleic acid detection capability of DNA microarrays. Current expression arrays, however, are expensive and inflexible. They are custom designed for each organism and they do not offer the possibility of incorporating updated genomic information without production of a new chip. One possible solution is the development of a universal chip, consisting of all 4n possible DNA sequences of length n. Studying different organisms or new genes would simply require modifications to the hybridization pattern analysis software. The key problem is to find a value of n that is large enough to afford sufficient specificity, yet is small enough for practical fabrication and readout. We developed an analytical model, supported by computer-assisted calculation with yeast and mouse transcript data, to argue that it is both practical and useful to fabricate n-mer arrays with 10 < or = n < or = 16. PMID- 11779838 TI - Analysis of the 5S RNA pool in Arabidopsis thaliana: RNAs are heterogeneous and only two of the genomic 5S loci produce mature 5S RNA. AB - One major 5S RNA, 120 bases long, was revealed by an analysis of mature 5S RNA from tissues, developmental stages, and polysomes in Arabidopsis thaliana. Minor 5S RNA were also found, varying from the major one by one or two base substitutions; 5S rDNA units from each 5S array of the Arabidopsis genome were isolated by PCR using CIC yeast artificial chromosomes (YACs) mapped on the different loci. By using a comparison of the 5S DNA and RNA sequences, we could show that both major and minor 5S transcripts come from only two of the genomic 5S loci: chromosome 4 and chromosome 5 major block. Other 5S loci are either not transcribed or produce rapidly degraded 5S transcripts. Analysis of the 5'- and 3'-DNA flanking sequence has permitted the definition of specific signatures for each 5S rDNA array. PMID- 11779840 TI - Enzymatic regional methylation assay: a novel method to quantify regional CpG methylation density. AB - We have developed a novel quantitative method for rapidly assessing the CpG methylation density of a DNA region in mammalian cells. After bisulfite modification of genomic DNA, the region of interest is PCR amplified with primers containing two dam sites (GATC). The purified PCR products are then incubated with 14C-labeled S-adenosyl-L-methionine (SAM) and dam methyltransferase as an internal control to standardize DNA quantity. This is followed by an incubation with 3H-labeled SAM and SssI methyltransferase for methylation quantification. By use of standard mixtures of cell line DNA with a defined methylation status in every assay, the ratio (3H/14C signal) of each sample can be converted into percentage values to assess the methylation density of the amplified sequence. This methylation-sensitive technique, termed ERMA (Enzymatic Regional Methylation Assay) provides several advantages over existing methods used for methylation analysis as it determines an exact measurement of the methylation density of the region studied. We demonstrate a use of this technique in determining the methylation density of the promoter region of the tumor suppressor gene p15INK4B and changes that occur after treatment with demethylating agents. PMID- 11779841 TI - Methylation-specific oligonucleotide microarray: a new potential for high throughput methylation analysis. AB - Oligonucleotide microarray-based hybridization is an emerging technology for genome-wide detection of DNA variations. We have extended this principle and developed a novel approach, called methylation-specific oligonucleotide (MSO) microarray, for detecting changes of DNA methylation in cancer. The method uses bisulfite-modified DNA as a template for PCR amplification, resulting in conversion of unmethylated cytosine, but not methylated cytosine, into thymine within CpG islands of interest. The amplified product, therefore, may contain a pool of DNA fragments with altered nucleotide sequences due to differential methylation status. A test sample is hybridized to a set of oligonucleotide (19 23 nucleotides in length) arrays that discriminate methylated and unmethylated cytosine at specific nucleotide positions, and quantitative differences in hybridization are determined by fluorescence analysis. A unique control system is also implemented to test the accuracy and reproducibility of oligonucleotides designed for microarray hybridization. This MSO microarray was applied to map methylated CpG sites within the human estrogen receptor alpha (ERalpha) gene CpG island in breast cancer cell lines, normal fibroblasts, breast tumors, and normal controls. Methylation patterns of the breast cancer cell lines, determined by MSO microarray, were further validated by bisulfite nucleotide sequencing (P <0.001). This proof-of-principle study shows that MSO microarray is a promising technique for mapping methylation changes in multiple CpG island loci and for generating epigenetic profiles in cancer. PMID- 11779842 TI - Finding genes in the C2C12 osteogenic pathway by k-nearest-neighbor classification of expression data. AB - A supervised classification scheme for analyzing microarray expression data, based on the k-nearest-neighbor method coupled to noise-reduction filters, has been used to find genes involved in the osteogenic pathway of the mouse C2C12 cell line studied here as a model for in vivo osteogenesis. The scheme uses as input a training set embodying expert biological knowledge, and provides internal estimates of its own misclassification errors, which furthermore enables systematic optimization of the classifier parameters. On the basis of the C2C12 generated expression data set with 34,130 expression profiles across 2 time courses, each comprised of 6 points, and a training set containing known members of the osteogenic, myoblastic, and adipocytic pathways, 176 new genes in addition to 28 originally in the training set are selected as relevant to osteogenesis. For this selection, the estimated sensitivity is 42% and the posterior false positive rate (fraction of candidates that are spurious) is 12%. The corresponding sensitivity and false-positive rate for detection of myoblastic genes are 9% and 31%, respectively, and only 4% and approximately 100%, respectively, for adipocytic genes, in accordance with an experimental design that predominantly stimulated the osteogenic pathway. Validation of this selection is provided by examining expression of the genes in an independent biological assay involving mouse calvaria (skull bone) primary cell cultures, in which a large fraction of the 176 genes are seen to be strongly regulated, as well as by case-by-case analysis of the genes on the basis of expert domain knowledge. The methodology should be generalizable to any situation in which enough a priori biological knowledge exists to define a training set. PMID- 11779843 TI - ARACHNE: a whole-genome shotgun assembler. AB - We describe a new computer system, called ARACHNE, for assembling genome sequence using paired-end whole-genome shotgun reads. ARACHNE has several key features, including an efficient and sensitive procedure for finding read overlaps, a procedure for scoring overlaps that achieves high accuracy by correcting errors before assembly, read merger based on forward-reverse links, and detection of repeat contigs by forward-reverse link inconsistency. To test ARACHNE, we created simulated reads providing approximately 10-fold coverage of the genomes of H. influenzae, S. cerevisiae, and D. melanogaster, as well as human chromosomes 21 and 22. The assemblies of these simulated reads yielded nearly complete coverage of the respective genomes, with a small number of contigs joined into a smaller number of supercontigs (or scaffolds). For example, analysis of the D. melanogaster genome yielded approximately 98% coverage with an N50 contig length of 324 kb and an N50 supercontig length of 5143 kb. The assembly accuracy was high, although not perfect: small errors occurred at a frequency of roughly 1 per 1 Mb (typically, deletion of approximately 1 kb in size), with a very small number of other misassemblies. The assembly was rapid: the Drosophila assembly required only 21 hours on a single 667 MHz processor and used 8.4 Gb of memory. PMID- 11779844 TI - Linker-mediated recombinational subcloning of large DNA fragments using yeast. AB - The homologous recombination pathway in yeast is an ideal tool for the sequence specific assembly of plasmids. Complementary 80-nucleotide oligonucleotides that overlap a vector and a target fragment were found to serve as efficient recombination linkers for fragment subcloning. Using electroporation, single stranded 80-mers were adequate for routine plasmid construction. A cycloheximide based counterselection was introduced to increase the specificity of cloning by homologous recombination relative to nonspecific vector background. Reconstruction experiments suggest this counterselection increased cloning specificity by 100-fold. Cycloheximide counterselection was used in conjunction with 80-bp linkers to subclone targeted regions from bacterial artificial chromosomes. This technology may find broad application in the final stages of completing the Human Genome Sequencing Project and in applications of BAC clones to the functional analysis of complex genomes. PMID- 11779845 TI - The K(A)/K(S) ratio test for assessing the protein-coding potential of genomic regions: an empirical and simulation study. AB - Comparative genomics is a simple, powerful way to increase the accuracy of gene prediction. In this study, we show the utility of a simple test for the identification of protein-coding exons using human/mouse sequence comparisons. The test takes advantage of the fact that in the vast majority of coding regions, synonymous substitutions (K(S)) occur much more frequently than nonsynonymous ones (K(A)) and uses the K(A)/K(S) ratio as the criterion. We show the following: (1) most of the human and mouse exons are sufficiently long and have a suitable degree of sequence divergence for the test to perform reliably; (2) the test is suited for the identification of long exons and single exon genes, which are difficult to predict by current methods; (3) the test has a false-negative rate, lower than most of current gene prediction methods and a false-positive rate lower than all current methods; (4) the test has been automated and can be used in combination with other existing gene-prediction methods. PMID- 11779846 TI - Associating genes with gene ontology codes using a maximum entropy analysis of biomedical literature. AB - Functional characterizations of thousands of gene products from many species are described in the published literature. These discussions are extremely valuable for characterizing the functions not only of these gene products, but also of their homologs in other organisms. The Gene Ontology (GO) is an effort to create a controlled terminology for labeling gene functions in a more precise, reliable, computer-readable manner. Currently, the best annotations of gene function with the GO are performed by highly trained biologists who read the literature and select appropriate codes. In this study, we explored the possibility that statistical natural language processing techniques can be used to assign GO codes. We compared three document classification methods (maximum entropy modeling, naive Bayes classification, and nearest-neighbor classification) to the problem of associating a set of GO codes (for biological process) to literature abstracts and thus to the genes associated with the abstracts. We showed that maximum entropy modeling outperforms the other methods and achieves an accuracy of 72% when ascertaining the function discussed within an abstract. The maximum entropy method provides confidence measures that correlate well with performance. We conclude that statistical methods may be used to assign GO codes and may be useful for the difficult task of reassignment as terminology standards evolve over time. PMID- 11779847 TI - Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity. AB - Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate chains of proteoglycan, a component of blood vessel walls and the extracellular matrix. Recent studies demonstrated that HPR1 expression is increased in a variety of malignancies and may play a critical role in tumor metastases. The HPR1 gene and its genomic structure have been recently cloned and characterized. To understand the mechanisms of HPR1 gene expression and regulation, we first mapped the transcription start site of the HPR1 gene and found that HPR1 mRNA was transcribed from the nucleotide position 101 bp upstream of the ATG codon. A 3.5-kb promoter region of the HPR1 gene was cloned. Sequence analysis revealed that the TATA-less, GC-rich promoter of the HPR1 gene belongs to the family of housekeeping genes. This 3.5-kb promoter region exhibited strong promoter activity in two thyroid tumor cell lines. Truncation analysis of the HPR1 promoter identified a minimal 0.3-kb region that had strong basal promoter activity. Truncation and mutational analysis of the HPR1 promoter revealed three Sp1 sites and four Ets-relevant elements (ERE) significantly contributing to basal HPR1 promoter activity. Binding to the Sp1 sites by Sp1 and to the ERE sites by GA-binding protein (GABP) was confirmed by electrophoretic mobility shift assay and competition and supershift electrophoretic mobility shift assays. Cotransfection of Sp- and GABP-deficient Drosophila SL-2 cells with the HPR1 promoter-driven luciferase construct plus the expression vector encoding the Sp1, Sp3, or GABP gene induced luciferase gene expression. Mutation or truncation of the Sp1 or ERE sites reduced luciferase expression in both SL-2 cells and thyroid tumor cell lines. Coexpression of GABPalpha/beta and Sp1 or Sp3 further increased luciferase reporter gene expression. Our results collectively suggest that Sp1 cooperates with GABP to regulate HPR1 promoter activity. PMID- 11779848 TI - Functional domains of histone deacetylase-3. AB - Post-translational modifications of histones, in general, and acetylation/deacetylation, in particular, can dramatically alter gene expression in eukaryotic cells. In humans, four highly homologous class I HDAC enzymes (HDAC1, HDAC2, HDAC3, and HDAC8) have been identified to date. Although HDAC3 shares some structural and functional similarities with other class I HDACs, it exists in multisubunit complexes separate and different from other known HDAC complexes, implying that individual HDACs might function in a distinct manner. In this current study, to understand further the cellular function of HDAC3 and to uncover possible unique roles this protein may have in gene regulation, we performed a detailed analysis of HDAC3 using deletion mutations. Surprisingly, we found that the non-conserved C-terminal region of HDAC3 is required for both deacetylase and transcriptional repression activity. In addition, we discovered that the central portion of the HDAC3 protein possesses a nuclear export signal, whereas the C-terminal part of HDAC3 contributes to the protein's localization in the nucleus. Finally, we found that HDAC3 forms oligomers in vitro and in vivo and that the N-terminal portion of HDAC3 is necessary for this property. These data indicate that HDAC3 comprises separate, non-overlapping domains that contribute to the unique properties and function of this protein. PMID- 11779849 TI - An mRNA splice variant of the AFX gene with altered transcriptional activity. AB - Several studies indicate that FKHR and AFX, mammalian homologues of the Caenorhabditis elegans forkhead transcription factor DAF-16, function in the insulin signaling pathway. Here we describe the discovery of a novel AFX isoform, which we designated AFX zeta, in which the first 16 amino acids of the forkhead domain are not present. PCR analysis showed that this isoform is most abundant in the liver, kidney, and pancreas. In HepG2 cells, overexpressed AFX zeta induced reporter gene activity through the insulin-responsive sequences of the phosphoenolpyruvate carboxykinase (PEPCK), IGFBP-1, and G6Pase promoters. AFX zeta-mediated stimulation was repressed by insulin treatment, by bisperoxovanadate treatment, and by overexpression of constitutively active protein kinase B (PKB). Insulin treatment and PKB overexpression resulted in phosphorylation of AFX zeta. Furthermore, 5-aminoimidazole-4-carboxamide-1-beta-d ribofuranoside (AICAR), an AMP-activated protein kinase activator, repressed AFX zeta-dependent reporter activation. Taken together, these findings suggest that AFX zeta is a downstream target of both the phosphatidylinositol 3-kinase/PKB insulin signaling pathway and an AMP-activated protein kinase-dependent pathway. PMID- 11779850 TI - Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1 degradation. AB - Signaling via the phosphoinositide 3-kinase (PI3K)/AKT pathway is crucial for the regulation of endothelial cell (EC) proliferation and survival, which involves the AKT-dependent phosphorylation of the DNA repair protein p21(Cip1) at Thr-145. Because p21(Cip1) is a short-lived protein with a high proteasomal degradation rate, we investigated the regulation of p21(Cip1) protein levels by PI3K/AKT dependent signaling. The PI3K inhibitors Ly294002 and wortmannin reduced p21(Cip1) protein abundance in human umbilical vein EC. However, mutation of the AKT site Thr-145 into aspartate (T145D) did not increase its protein half-life. We therefore investigated whether a kinase downstream of AKT regulates p21(Cip1) protein levels. In various cell types, AKT phosphorylates and inhibits glycogen synthase kinase-3 (GSK-3). Upon serum stimulation of EC, GSK-3beta was phosphorylated at Ser-9. Site-directed mutagenesis revealed that GSK-3 in vitro phosphorylated p21(Cip1) specifically at Thr-57 within the Cdk binding domain. Overexpression of GSK-3beta decreased p21(Cip1) protein levels in EC, whereas the specific inhibition of GSK-3 with lithium chloride interfered with p21(Cip1) degradation and increased p21(Cip1) protein about 10-fold in EC and cardiac myocytes (30 mm, p < 0.001). These data indicate that GSK-3 triggers p21(Cip1) degradation. In contrast, stimulation of AKT increases p21(Cip1) via inhibitory phosphorylation of GSK-3. PMID- 11779851 TI - Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. AB - Serine/threonine kinase Akt is thought to mediate many biological actions toward anti-apoptotic responses. Screening of drugs that could interfere with the Akt signaling pathway revealed that Hsp90 inhibitors (e.g. geldanamycin, radicicol, and its analogues) induced Akt dephosphorylation, which resulted in Akt inactivation and apoptosis of the cells. Hsp90 inhibitors did not directly affect Akt kinase activity in vitro. Thus, we examined the effects of Hsp90 inhibitors on upstream Akt kinases, phosphatidylinositide-3-OH kinase (PI3K) and 3 phosphoinositide-dependent protein kinase-1 (PDK1). Hsp90 inhibitors had no effect on PI3K protein expression. In contrast, treatment of the cells with Hsp90 inhibitors decreased the amount of PDK1 without directly inhibiting PDK1 kinase activity. We found that the kinase domain of PDK1 was essential for complex formation with Hsp90 and that Hsp90 inhibitors suppressed PDK1 binding to Hsp90. PDK1 degradation mechanisms revealed that inhibition of PDK1 binding to Hsp90 caused proteasome-dependent degradation of PDK1. Treatment of proteasome inhibitors increased the amount of detergent-insoluble PDK1 in Hsp90 inhibitor treated cells. Therefore, the association of PDK1 with Hsp90 regulates its stability, solubility, and signaling. Because Akt binding to Hsp90 is also involved in the maintenance of Akt kinase activity, Hsp90 plays an important role in PDK1-Akt survival signaling pathway. PMID- 11779852 TI - The fluorescence spectrum of the introduced tryptophans in the alpha 3(beta F155W)3gamma subcomplex of the F1-ATPase from the thermophilic Bacillus PS3 cannot be used to distinguish between the number of nucleoside di- and triphosphates bound to catalytic sites. AB - It has been reported that shifts in the fluorescence emission spectrum of the introduced tryptophans in the betaF155W mutant of Escherichia coli F(1) (bovine heart mitochondria F(1) residue number) can quantitatively distinguish between the number of catalytic sites occupied with ADP and ATP during steady-state ATP hydrolysis (Weber, J., Bowman, C., and Senior, A. E. (1996) J. Biol. Chem. 271, 18711--18718). In contrast, addition of MgADP, Mg-5'-adenylyl beta,gamma imidophosphate (MgAMP-PNP), and MgATP in 1:1 ratios to the alpha(3)(betaF155W)(3)gamma subcomplex of thermophilic Bacillus PS3 F(1) (TF(1)) induced nearly identical blue shifts in the fluorescence emission maximum that was accompanied by quenching. Addition of 2 mm MgADP induced a slightly greater blue shift and a slight increase in intensity over those observed with 1:1 MgADP. However, addition of 2 mm MgAMP-PNP or MgATP induced a much greater blue shift and substantially enhanced fluorescence intensity over those observed in the presence of stoichiometric MgADP or MgAMP-PNP. It is clear from these results that the fluorescence spectrum of the introduced tryptophans in the betaF155W mutant of TF(1) does not respond in regular increments at any wavelength as catalytic sites are filled with nucleotides. The fluorescence spectrum observed after entrapping MgADP-fluoroaluminate complexes in two catalytic sites of the betaF155W subcomplex indicates that the fluorescence emission spectrum of the enzyme is maximally perturbed when nucleotides are bound to two catalytic sites. This finding is consistent with accumulating evidence suggesting that only two beta subunits in the alpha(3)beta(3)gamma subcomplex of TF(1) can simultaneously exist in the completely closed conformation. PMID- 11779853 TI - The Rpb9 subunit of RNA polymerase II binds transcription factor TFIIE and interferes with the SAGA and elongator histone acetyltransferases. AB - Rpb9 is a small subunit of yeast RNA polymerase II participating in elongation and formed of two conserved zinc domains. rpb9 mutants are viable, with a strong sensitivity to nucleotide-depleting drugs. Deleting the C-terminal domain down to the first 57 amino acids has no detectable growth defect. Thus, the critical part of Rpb9 is limited to a N-terminal half that contacts the lobe of the second largest subunit (Rpb2) and forms a beta-addition motif with the "jaw" of the largest subunit (Rpb1). Rpb9 has homology to the TFIIS elongation factor, but mutants inactivated for both proteins are indistinguishable from rpb9 single mutants. In contrast, rpb9 mutants are lethal in cells lacking the histone acetyltransferase activity of the RNA polymerase II Elongator and SAGA factors. In a two-hybrid test, Rpb9 physically interacts with Tfa1, the largest subunit of TFIIE. The interacting fragment, comprising amino acids 62-164 of Tfa1, belongs to a conserved zinc motif. Tfa1 is immunoprecipitated by RNA polymerase II. This co-purification is strongly reduced in rpb9-Delta, suggesting that Rpb9 contributes to the recruitment of TFIIE on RNA polymerase II. PMID- 11779854 TI - Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome. AB - A yeast two-hybrid screen with the human S6 (TBP7, RPT3) ATPase of the 26 S proteasome has identified gankyrin, a liver oncoprotein, as an interacting protein. Gankyrin interacts with both free and regulatory complex-associated S6 ATPase and is not stably associated with the 26 S particle. Deletional mutagenesis shows that the C-terminal 78 amino acids of the S6 ATPase are necessary and sufficient to mediate the interaction with gankyrin. Deletion of an orthologous gene in Saccharomyces cerevisiae suggests that it is dispensable for cell growth and viability. Overexpression and precipitation of tagged gankyrin from cultured cells detects a complex containing co-transfected tagged S6 ATPase (or endogenous S6) and endogenous cyclin D-dependent kinase CDK4. The proteasomal ATPases are part of the AAA (ATPases associated with diverse cellular activities) family, members of which are molecular chaperones; gankyrin complexes may therefore influence CDK4 function during oncogenesis. PMID- 11779856 TI - A conserved glutamate residue exhibits multifunctional catalytic roles in D fructose-1,6-bisphosphate aldolases. AB - The aldolase catalytic cycle consists of a number of proton transfers that interconvert covalent enzyme intermediates. Glu-187 is a conserved amino acid that is located in the mammalian fructose-1,6-bisphosphate aldolase active site. Its central location, within hydrogen bonding distance of three other conserved active site residues: Lys-146, Glu-189, and Schiff base-forming Lys-229, makes it an ideal candidate for mediating proton transfers. Point mutations, Glu-187--> Gln, Ala, which would inhibit proton transfers significantly, compromise activity. Trapping of enzymatic intermediates in Glu-187 mutants defines a proton transfer role for Glu-187 in substrate cleavage and Schiff base formation. Structural data show that loss of Glu-187 negative charge results in hydrogen bond formation between Lys-146 and Lys-229 consistent with a basic pK(a) for Lys 229 in native enzyme and supporting nucleophilic activation of Lys-229 by Glu-187 during Schiff base formation. The crystal structures also substantiate Glu-187 and Glu-189 as present in ionized form in native enzyme, compatible with their role of catalyzing proton exchange with solvent as indicated from solvent isotope effects. The proton exchange mechanism ensures Glu-187 basicity throughout the catalytic cycle requisite for mediating proton transfer and electrostatic stabilization of ketamine intermediates. Glutamate general base catalysis is a recurrent evolutionary feature of Schiff base0forming aldolases. PMID- 11779855 TI - Doxorubicin induces apoptosis and CD95 gene expression in human primary endothelial cells through a p53-dependent mechanism. AB - Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Here we show that doxorubicin (Dox), a drug used in antitumor therapy, triggered a marked accumulation of p53 and induced CD95 gene expression and apoptosis in proliferating human umbilical vein endothelial cells (HUVECs). Transfection and site-directed mutagenesis experiments using the CD95 promoter fused to an intronic enhancer indicated the requirement for a p53 site for Dox-induced promoter activation. Furthermore, the p53 inhibitor pifithrin alpha (PFT-alpha) blocked both promoter inducibility and protein up-regulation of CD95 in response to Dox. Up-regulated CD95 in Dox-treated cells was functional in eliciting apoptosis upon incubation of the cells with an agonistic CD95 antibody. However, Dox-mediated apoptosis was independent of CD95/CD95L interaction. The analysis of apoptosis in the presence of PFT-alpha and benzyloxycarbonyl-Val-Ala dl-Asp-fluoromethylketone revealed that both p53 and caspase activation are required for Dox-mediated apoptosis of HUVECs. Finally, Dox triggered Bcl-2 down regulation, cytochrome c release from mitochondria, and the activation of caspases 9 and 3, suggesting the involvement of a mitochondrially operated pathway of apoptosis. These results highlight the role of p53 in the response of primary endothelial cells to genotoxic drugs and may reveal a novel mechanism underlying the antitumoral properties of Dox, related to its ability to induce apoptosis in proliferating endothelial cells. PMID- 11779857 TI - The transmembrane segment of ryanodine receptor contains an intracellular membrane retention signal for Ca(2+) release channel. AB - The ryanodine receptor (RyR) is a large homotetrameric protein with a hydrophobic domain at the C-terminal end that resides in the endoplasmic reticulum (ER) or sarcoplasmic reticulum membrane and forms the conduction pore of a Ca(2+) release channel. Our previous studies showed that RyR expressed in heterologous cells localized to the ER membrane. Confocal microscopic imaging indicated that the ER retention signal is likely present within the C-terminal portion of RyR, a region that contains four putative transmembrane segments. To identify the amino acid sequence responsible for ER retention of RyR, we expressed fusion proteins containing intercellular adhesion molecule (ICAM), various fragments of RyR, and green fluorescent protein (GFP) in Chinese hamster ovary and COS-7 cells. ICAM is a plasma membrane-resident glycoprotein and serves as a reporter for protein trafficking to the cell surface membrane. Imaging analyses indicated that ICAM GFP fusion proteins with RyR sequence preceding the four transmembrane segments, ICAM-RyR-(3661-3993)-GFP, and with RyR sequence corresponding to transmembrane segments 1, 2, and 3, ICAM-RyR-(4558-4671)-GFP and ICAM-RyR-(4830-4919)-GFP, were localized to the plasma membrane; fusion proteins containing the fourth transmembrane segment of RyR, ICAM-RyR-(4913-4943)-GFP, were retained in the ER. Biochemical assay showed that ICAM-RyR-GFP fusion proteins that target to the plasma membrane are fully glycosylated, and those retained in the intracellular membrane are core-glycosylated. Together our data indicate that amino acids 4918 4943 of RyR contain the signal sequence for ER retention of the Ca(2+) release channel. PMID- 11779858 TI - A novel zinc finger transcription factor with two isoforms that are differentially repressed by estrogen receptor-alpha. AB - Estrogen receptor-alpha (ERalpha) can induce the expression of genes in response to estrogen by binding to estrogen response elements in the promoters of target genes. There is growing evidence that ERalpha can alter patterns of gene expression in response to ligand by regulating the activity of other factors through a direct protein-protein interaction. To identify other factors that are regulated by ERalpha, a yeast two-hybrid screen was performed that identified a novel Cys(2)His(2) zinc finger protein named ZER6. The ZER6 protein contains a Kruppel-associated box domain and six Cys(2)His(2) zinc fingers. Transcripts from the ZER6 gene can have alternate 5' exons and encode either a p71 or p52 isoform. The p52-ZER6 protein interacts strongly with ERalpha in the presence of 17beta estradiol, whereas the p71-ZER6 isoform has a HUB-1 amino-terminal domain that inhibits the interaction with ERalpha. A consensus ZER6 binding element was defined using PCR-assisted binding site selection. In COS-1 cells, both the p52 and p71 isoforms can activate transcription through the ZER6 binding element; however, in the presence of ERalpha, transactivation by the p52 isoform is specifically repressed. Overexpression of the p52 isoform was able to abrogate activation by p71-ZER6. Expression of ZER6 was largely restricted to the mammary gland with a lower level of expression in the kidney. We conclude that ZER6 is a novel zinc finger transcription factor in which regulation of transcription in hormone-responsive cells can be controlled by the relative level of expression of two distinct isoforms. PMID- 11779859 TI - Oligomerization through hemopexin and cytoplasmic domains regulates the activity and turnover of membrane-type 1 matrix metalloproteinase. AB - The formation of multimeric complexes by membrane-type 1 matrix metalloproteinase (MT1-MMP) may facilitate its autocatalytic inactivation or proMMP-2 activation on the cell surface. To characterize these processes, we expressed various glutathione S-transferase/MT1-MMP fusion proteins in human HT-1080 fibrosarcoma cells and SV40-transformed lung fibroblasts and analyzed their effects on MT1-MMP activity and potential homophilic interactions. We report here that MT1-MMP is expressed on the cell surface as oligomeric 200--240-kDa complexes containing both the active 60-kDa and autocatalytically processed 43-kDa species. Overexpression of a glutathione S-transferase/MT1-MMP fusion protein containing the transmembrane and cytoplasmic domains of MT1-MMP inhibited the phorbol 12 myristate 13-acetate-induced autocatalytic cleavage of endogenous MT1-MMP to the 43-kDa species, but not proMMP-2 activation. On the other hand, a similar fusion protein with the hemopexin, transmembrane, and cytoplasmic domains inhibited proMMP-2 activation in a dominant-negative fashion. These results suggest that both the autocatalytic cleavage of MT1-MMP and proMMP-2 activation may be regulated by oligomerization through the cytoplasmic and hemopexin domains. Indeed, either domain, when attached to the cell membrane by a transmembrane domain, formed stable homophilic complexes. Copurification of MT1-MMP with these fusion proteins correlated with their cell-surface co-localization. Thus, MT1-MMP oligomerization through the hemopexin, transmembrane, and cytoplasmic domains controls its catalytic activity. PMID- 11779860 TI - Regulation of insulin-like growth factor I receptor dephosphorylation by SHPS-1 and the tyrosine phosphatase SHP-2. AB - Activation of insulin-like growth factor I receptor (IGF-IR) kinase is an important site of control of IGF-I-linked intracellular signaling pathways. One potentially important regulatory variable is IGF-IR dephosphorylation. It has been shown that SHP-2, a tyrosine phosphatase, can bind to the activated IGF-IR in vitro; however, its role in IGF-IR dephosphorylation in whole cells is unknown. These studies were undertaken to determine whether SHP-2 was a candidate for mediating IGF-IR dephosphorylation. The IGF-IR in smooth muscle cells was dephosphorylated rapidly beginning 10 min after ligand addition, and this was temporally associated with SHP-2 binding to the receptor. IGF-I stimulated SHPS-1 phosphorylation and the subsequent recruitment of SHP-2. In cells expressing a SHPS-1 mutant that did not bind SHP-2 there was no recruitment of SHP-2 to the IGF-IR. Cells expressing a catalytically inactive form of SHP-2 showed SHP-2 recruitment to SHPS-1, but this did not result in SHPS-1 dephosphorylation, and there was a prolonged IGF-IR phosphorylation response after IGF-I stimulation. These studies indicate that IGF-IR stimulates phosphorylation of SHPS-1 which is critical for SHP-2 recruitment to the plasma membrane and for its recruitment to the IGF-IR. Recruitment of SHP-2 to the receptor then results in receptor dephosphorylation. The regulation of this process may be an important determinant of IGF-IR-mediated signaling. PMID- 11779861 TI - Regulation of osmotic stress-responsive gene expression by the LOS6/ABA1 locus in Arabidopsis. AB - Drought and high salinity induce the expression of many plant genes. To understand the signal transduction mechanisms underlying the activation of these genes, we carried out a genetic screen to isolate Arabidopsis mutants defective in osmotic stress-regulated gene induction. Here we report the isolation, characterization, and cloning of a mutation, los6, which diminished osmotic stress activation of a reporter gene. RNA blot analysis indicates that under osmotic stress the transcript levels for stress-responsive genes such as RD29A, COR15A, KIN1, COR47, RD19, and ADH are lower in los6 plants than in wild type plants. los6 plants were found to have reduced phytohormone abscisic acid (ABA) accumulation and to be allelic to the ABA-deficient mutant, aba1. LOS6/ABA1 encodes a zeaxanthin epoxidase that functions in ABA biosynthesis. Its expression is enhanced by osmotic stress. Furthermore, we found that there exists a positive feedback regulation by ABA on the expression of LOS6/ABA1, which may underscore a quick adaptation strategy for plants under osmotic stress. Similar positive regulation by ABA also exists for other ABA biosynthesis genes AAO3 and LOS5/ABA3 and in certain genetic backgrounds, NCED3. This feedback regulation by ABA is impaired in the ABA-insensitive mutant abi1 but not in abi2. Moreover, the up regulation of LOS6/ABA1, LOS5/ABA3, AAO3, and NCED3 by osmotic stress is reduced substantially in ABA-deficient mutants. Transgenic plants overexpressing LOS6/ABA1 showed an increased RD29A-LUC expression under osmotic stress. These results suggest that the level of gene induction by osmotic stress is dependent on the dosage of the zeaxanthin epoxidase enzyme. PMID- 11779862 TI - The crystal structure and mechanism of 1-L-myo-inositol- 1-phosphate synthase. AB - 1-l-myo-Inositol-1-phosphate synthase catalyzes the conversion of d-glucose 6 phosphate to 1-l-myo-inositol-1-phosphate (MIP), the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, intramolecular aldol cyclization, and reduction. We have determined the first crystal structure of MIP synthase. We present structures of both the NAD-bound enzyme and the enzyme bound to an inhibitor, 2-deoxy-glucitol-6 phosphate. While 58 amino acids are disordered in the unbound form of the enzyme in the vicinity of the active site, the inhibitor nucleates the folding of this domain in a striking example of induced fit, serving to completely encapsulate it within the enzyme. Three helices and a long beta-strand are formed in this process. We postulate a mechanism for the conversion based on the structure of the inhibitor-bound complex. PMID- 11779863 TI - Transactivation of ErbB2 and ErbB3 by tumor necrosis factor-alpha and anisomycin leads to impaired insulin signaling through serine/threonine phosphorylation of IRS proteins. AB - The cellular pathways involved in the impairment of insulin signaling by cellular stress, triggered by the inflammatory cytokine tumor necrosis factor-alpha (TNF) or by translational inhibitors like cycloheximide and anisomycin were studied. Similar to TNF, cycloheximide and anisomycin stimulated serine phosphorylation of IRS-1 and IRS-2, reduced their ability to interact with the insulin receptor, inhibited the insulin-induced tyrosine phosphorylation of IRS proteins, and diminished their association with phosphatidylinositol 3-kinase (PI3K). These defects were partially reversed by wortmannin and LY294002, indicating that a PI3K-regulated step is critical for the impairment of insulin signaling by cellular stress. Induction of cellular stress resulted in complex formation between PI3K and ErbB2/ErbB3 and enhanced PI3K activity, implicating ErbB proteins as downstream effectors of stress-induced insulin resistance. Indeed, stimulation of ErbB2/ErbB3 by NDFbeta1, the ErbB3 ligand, inhibited IRS protein tyrosine phosphorylation and recruitment of downstream effectors. Specific inhibitors of the ErbB2 tyrosine kinase abrogated the activation of ErbB2/ErbB3 and in parallel prevented the reduction in IRS protein functions. Taken together, our results suggest a novel mechanism by which cellular stress induces cross-talk between two different signaling pathways. Stress-dependent transactivation of ErbB2/ErbB3 receptors triggers a PI3K cascade that induces serine phosphorylation of IRS proteins culminating in insulin resistance. PMID- 11779865 TI - Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D. AB - The endosomal compartment of hepatic parenchymal cells contains an acidic endopeptidase, endosomal acidic insulinase, which hydrolyzes internalized insulin and generates the major primary end product A(1--21)-B(1--24) insulin resulting from a major cleavage at residues Phe(B24)-Phe(B25). This study addresses the nature of the relevant endopeptidase activity in rat liver that is responsible for most receptor-mediated insulin degradation in vivo. The endosomal activity was shown to be aspartic acid protease cathepsin D (CD), based on biochemical similarities to purified CD in 1) the rate and site of substrate cleavage, 2) pH optimum, 3) sensitivity to pepstatin A, and 4) binding to pepstatin A-agarose. The identity of the protease was immunologically confirmed by removal of greater than 90% of the insulin-degrading activity associated with an endosomal lysate using polyclonal antibodies to CD. Moreover, the elution profile of the endosomal acidic insulinase activity on a gel-filtration TSK-GEL G3000 SW(XL) high performance liquid chromatography column corresponded exactly with the elution profile of the immunoreactive 45-kDa mature form of endosomal CD. Using nondenaturating immunoprecipitation and immunoblotting procedures, other endosomal aspartic acid proteases such as cathepsin E and beta-site amyloid precursor protein-cleaving enzyme (BACE) were ruled out as candidate enzymes for the endosomal degradation of internalized insulin. Immunofluorescence studies showed a largely vesicular staining pattern for internalized insulin in rat hepatocytes that colocalized partially with CD. In vivo pepstatin A treatment was without any observable effect on the insulin receptor content of endosomes but augmented the phosphotyrosine content of the endosomal insulin receptor after insulin injection. These results suggest that CD is the endosomal acidic insulinase activity which catalyzes the rate-limiting step of the in vivo cleavage at the Phe(B24)-Phe(B25) bond, generating the inactive A(1--21)-B(1--24) insulin intermediate. PMID- 11779864 TI - Nab2p is required for poly(A) RNA export in Saccharomyces cerevisiae and is regulated by arginine methylation via Hmt1p. AB - From transcription to translation, mRNA is complexed with heterogeneous nuclear ribonucleoproteins (hnRNP proteins) that mediate mRNA processing, export from the nucleus, and delivery into the cytoplasm. Although the mechanism is unknown, export of mature mRNA from the nucleus is a critical regulatory step in gene expression. Analyses of hnRNP proteins have shown that many of these proteins are required for this essential cellular process. In this study, we characterize the Saccharomyces cerevisiae Nab2 protein, which was first identified as a poly(A) RNA-binding protein (Anderson, J. T., Wilson, S. M., Datar, K. V., and Swanson, M. S. (1993) Mol. Cell. Biol. 13, 2730-2741). Our work indicates that poly(A) RNA export from the nucleus is dependent upon a functional Nab2 protein; correspondingly, export of Nab2p from the nucleus is dependent upon ongoing RNA polymerase II transcription. Furthermore, we show that Nab2p is modified within its RGG domain by the type I protein-arginine methyltransferase, Hmt1p. Our experiments demonstrate that arginine methylation is required for the export of Nab2p from the nucleus and therefore establish an in vivo effect of this modification. Overall, these experiments provide evidence that Nab2p is an hnRNP protein that is required for poly(A) RNA export and whose export from the nucleus is regulated by Hmt1p. PMID- 11779866 TI - Heat induction of the unphosphorylated form of hypoxia-inducible factor-1alpha is dependent on heat shock protein-90 activity. AB - Hypoxia-inducible factor (HIF)-1alpha is the oxygen-sensitive subunit of HIF-1, a transcriptional master regulator of oxygen homeostasis. Oxygen-dependent prolyl hydroxylation targets HIF-1alpha for ubiquitinylation and proteasomal degradation. Unexpectedly, we found that exposing mice to elevated temperatures resulted in a strong HIF-1alpha induction in kidney, liver, and spleen. To elucidate the molecular mechanisms responsible for this effect, HepG2 hepatoma cells were exposed to different temperatures (34-42 degrees C) under normoxic (20% O(2)) or hypoxic (3% O(2)) conditions. Heat was sufficient to stabilize mainly a phosphatase-resistant, low molecular weight form of HIF-1alpha (termed HIF-1alpha(a)). Heat-induced HIF-1alpha(a) accumulated in the nucleus but neither bound to DNA nor trans-activated reporter or target gene expression, demonstrating the need for post-translational modifications for these functions. The protein banding pattern of heat-induced HIF-1alpha in immunoblot analyses was clearly distinct from the HIF-1alpha pattern after prolyl hydroxylase inhibition (by hypoxia or iron chelation/replacement) or following proteasome inhibition, suggesting that heat stabilizes HIF-1alpha by a novel mechanism. Inhibition of the ATP-dependent chaperone activity of HSP90 by novobiocin or geldanamycin prevented heat-induced as well as hypoxia-induced HIF-1alpha accumulation, indicating a common role of the HSP90 chaperone activity in HIF-1alpha stabilization by these two environmental parameters. PMID- 11779867 TI - Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity. AB - The transcription factor c-Myb is subject to several types of post-translational modifications, including phosphorylation, acetylation, and ubiquitination. These modifications regulate the transcription and transforming activity as well as the proteolytic stability of c-Myb. Here we report the covalent modification of c-Myb with the small ubiquitin-related protein SUMO-1. Mutational analysis identified two major sumolation sites (Lys(499) and Lys(523)) in the negative regulatory domain. Interestingly, the single mutation K523R completely abolished modification of c-Myb with SUMO-1, suggesting that sumolation of Lys(523) is required for modification of other lysines in c-Myb. In accordance with this observation, we found that the SUMO-1-conjugating enzyme Ubc9 interacted only with a region surrounding Lys(523) (also called the PEST/EVES motif). Experiments aimed at determining the proteolytic stability of sumolated and unmodified forms of c-Myb revealed that at least two covalently attached SUMO-1 molecules dramatically increased the stability of c-Myb. However, mutations of the SUMO-1 modification sites did not alter its stability, suggesting that a mechanism(s) other than competition of ubiquitin and SUMO-1 for the same lysine is involved in the stabilization of sumolated c-Myb protein. Finally, the K523R mutant of c-Myb, entirely deficient in sumolation, was shown to have an increased transactivation capacity on a Myb-responsive promoter, suggesting that SUMO-1 negatively regulates the transactivation function of c-Myb. Thus, modification of c-Myb with SUMO-1 represents a novel mechanism through which the negative regulatory domain can exert its suppressing activity on c-Myb transactivation capacity. PMID- 11779869 TI - Ca2+-dependent formation of a dynamin-synaptophysin complex: potential role in synaptic vesicle endocytosis. AB - Synaptophysin is a synaptic vesicle (SV) protein of unknown function. Here we show that a repeated sequence in the cytoplasmic tail of synaptophysin mediates the formation of a protein complex containing the GTPase dynamin. The formation of this complex requires a high Ca(2+) concentration, suggesting that it occurs preferentially at the sites of SV exocytosis. Coimmunoprecipitation of a dynamin synaptophysin complex from brain extracts is promoted by dissociation of vesicle associated membrane protein 2 from synaptophysin. This finding suggests that dynamin only associates with synaptophysin in vivo after vesicle-associated membrane protein 2 (VAMP2) enters the SNARE complex. GTP binding releases dynamin from synaptophysin, possibly serving to regulate dynamin selfassembly during endocytosis. Our results suggest that synaptophysin plays a role in SV recycling by recruiting dynamin to the vesicle membrane. PMID- 11779868 TI - Regulation of the mitogen-activated protein kinase signaling pathway by SHP2. AB - Gab1-SHP2 association is required for Erk mitogen-activated protein kinase activation by several growth factors. Gab1-SHP2 interaction activates SHP2. However, an activated SHP2 still needs to associate with Gab1 to mediate Erk activation. It was unclear whether SHP2 is required to dephosphorylate a negative phosphorylation site on Gab1 or whether SHP2 needs the Gab1 pleckstrin homology (PH) domain to target it to the plasma membrane. We found that expression of a fusion protein consisting of the Gab1 PH domain and an active SHP2 (Gab1PH SHP2DeltaN) induced constitutive Mek1 and Erk2 activation. Linking the active SHP2DeltaN to the PDK1 PH domain or the FRS2beta myristoylation sequence also induced Mek1 activation. Mek1 activation by Gab1PH-SHP2DeltaN was inhibited by an Src inhibitor and by Csk. Significantly, Gab1PH-SHP2DeltaN induced Src activation. Gab1PH-SHP2DeltaN expression activated Ras, and the Gab1PH-SHP2DeltaN induced Mek1 activation was blocked by RasN17. These findings suggest that Gab1PH SHP2DeltaN activated a signaling step upstream of Src and Ras. The SHP2 tyrosine phosphatase activity is essential for the function of the fusion protein. Together, these data show that the Gab1 sequence, besides the PH domain and SHP2 binding sites, is dispensable for Erk activation, suggesting that the primary role of Gab1 association with an activated SHP2 is to target it to the membrane. PMID- 11779870 TI - Nuclear organization of DNA replication initiation proteins in mammalian cells. AB - Origin recognition complex (ORC), CDC6, and MCM proteins assemble sequentially to form prereplication chromatin. However, their organization remains largely unclear in mammalian cells. Here we show that ORC1 proteins are associated with non-chromatin nuclear structures and assemble in nuclear foci in mammalian cells using an in vivo chemical cross-linking method. CDC6 proteins were also found to assemble in nuclear foci on non-chromatin nuclear structures, although their physical association with ORC1 has been undetectable. In contrast to the situation in yeast cells, CDC6 was found to remain associated with non-chromatin nuclear structures even after cells entered into S phase. Instead, ORC1 proteins were found to be degraded by a proteasome-dependent pathway during S phase. We also found that some ORC2 proteins are associated with non-chromatin nuclear structures like ORC1, although the remainder binds to nuclease-sensitive chromatin. Further analyses indicate that ORC2 physically interacts with ORC1 on non-chromatin nuclear structures. On the other hand, our results suggest that although a small proportion of MCM complexes are loaded onto chromatin regions near ORC foci, most of them are more widely distributed. Possible relations between such organization of prereplication chromatin and complicated origin specification in higher eukaryotic cells are discussed. PMID- 11779871 TI - Sp1 transcriptional activity is up-regulated by phosphatase 2A in dividing T lymphocytes. AB - We have followed Sp1 expression in primary human T lymphocytes induced, via CD2 plus CD28 costimulation, to sustained proliferation and subsequent return to quiescence. Binding of Sp1 to wheat germ agglutinin lectin was not modified following activation, indicating that the overall glycosylation of the protein was unchanged. Sp1 underwent, instead, a major dephosphorylation that correlated with cyclin A expression and, thus, with cell cycle progression. A similar change was observed in T cells that re-entered cell cycle following secondary interleukin-2 stimulation, as well as in serum-induced proliferating NIH/3T3 fibroblasts. Phosphatase 2A (PP2A) appears involved because 1) treatment of dividing cells with okadaic acid or cantharidin inhibited Sp1 dephosphorylation and 2) PP2A dephosphorylated Sp1 in vitro and strongly interacted with Sp1 in vivo. Sp1 dephosphorylation is likely to increase its transcriptional activity because PP2A overexpression potentiated Sp1 site-driven chloramphenicol acetyltransferase expression in dividing Kit225 T cells and okadaic acid reversed this effect. This increase might be mediated by a stronger affinity of dephosphorylated Sp1 for DNA, as illustrated by the reduced DNA occupancy by hyperphosphorylated Sp factors from cantharidin- or nocodazole-treated cells. Finally, Sp1 dephosphorylation appears to occur throughout cell cycle except for mitosis, a likely common feature to all cycling cells. PMID- 11779872 TI - Functional cooperation among Ras, STAT5, and phosphatidylinositol 3-kinase is required for full oncogenic activities of BCR/ABL in K562 cells. AB - BCR/ABL tyrosine kinase generated from the chromosomal translocation t(9;22) causes chronic myelogenous leukemia and acute lymphoblastic leukemia. To examine the roles of BCR/ABL-activated individual signaling molecules and their cooperation in leukemogenesis, we inducibly expressed a dominant negative (DN) form of Ras, phosphatidylinositol 3-kinase, and STAT5 alone or in combination in p210 BCR/ABL-positive K562 cells. The inducibly expressed DN Ras (N17), STAT5 (694F), and DN phosphatidylinositol 3-kinase (Delta p85) inhibited the growth by 90, 55, and 40%, respectively. During the growth inhibition, the expression of cyclin D2 and cyclin D3 was suppressed by N17, 694F, or Delta p85; that of cyclin E by N17; and that of cyclin A by Delta p85. In addition, N17 induced apoptosis in a small proportion of K562, whereas 694F and Delta p85 were hardly effective. In contrast, coexpression of two DN mutants in any combinations induced severe apoptosis. During these cultures, the expression of Bcl-2 was suppressed by N17, 694F, or Delta p85, and that of Bcl-XL by N17. Furthermore, although K562 was resistant to interferon-alpha- and dexamethasone-induced apoptosis, disruption of one pathway by N17, 694F, or Delta p85 sensitized K562 to these reagents. These results suggested that cooperation among these molecules is required for full leukemogenic activities of BCR/ABL. PMID- 11779873 TI - Characterization of the 23 S ribosomal RNA m5U1939 methyltransferase from Escherichia coli. AB - An Escherichia coli open reading frame, ygcA, was identified as a putative 23 S ribosomal RNA 5-methyluridine methyltransferase (Gustafsson, C., Reid, R., Greene, P. J., and Santi, D. V. (1996) Nucleic Acids Res. 24, 3756-3762). We have cloned, expressed, and purified the 50-kDa protein encoded by ygcA. The purified enzyme catalyzed the AdoMet-dependent methylation of 23 S rRNA but did not act upon 16 S rRNA or tRNA. A high performance liquid chromatography-based nucleoside analysis identified the reaction product as 5-methyluridine. The enzyme specifically methylated U1939 as determined by a nuclease protection assay and by methylation assays using site-specific mutants of 23 S rRNA. A 40-nucleotide 23 S rRNA fragment (nucleotide 1930--1969) also served as an efficient substrate for the enzyme. The apparent K(m) values for the 40-mer RNA oligonucleotide and AdoMet were 3 and 26 microm, respectively, and the apparent k(cat) was 0.06 s( 1). The enzyme contains two equivalents of iron/monomer and has a sequence motif similar to a motif found in iron-sulfur proteins. We propose to name this gene rumA and accordingly name the protein product as RumA for RNA uridine methyltransferase. PMID- 11779874 TI - The enteric parasite Entamoeba uses an autocrine catecholamine system during differentiation into the infectious cyst stage. AB - Enteric amoebae of the genus Entamoeba travel from host to host in an encysted form. We previously showed that in vitro cyst development of Entamoeba invadens requires the addition of defined amounts of multivalent galactose-terminated molecules, such as mucin, to the cultures. The amoeba surface lectin that binds mucin is presumed to convey transmembrane signals when clustered by the ligand, but the signaling molecules that function downstream of the lectin are not known. We report here that Entamoeba encystation was induced in the absence of galactose ligand when catecholamines were added to the encystation medium. Micromolar amounts of both epinephrine and norepinephrine induced encystation. Of a variety of synthetic catecholamine agonists tested, only beta(1)-adrenergic receptor agonists supported encystation, whereas alpha- and beta(2)-adrenergic receptor agonists did not. Only beta(1)-adrenergic receptor antagonists inhibited encystation, and did so even when exogenous catecholamines were not added, indicating that catecholamine binding is required for encystation and suggesting an endogenous source of the ligand. High performance liquid chromatography analysis of Entamoeba extracts showed that the amoebae themselves contain catecholamines and at least one of these is released when the cells are stimulated to encyst with galactose-terminated ligands. The presence of catecholamine binding sites on the surface of amoeba trophozoites was confirmed using radiolabeled catecholamine antagonist. Amoeba encystment was inhibited by addition of beta(1)-adrenergic receptor antagonist to cells that were stimulated to differentiate with either galactose ligand or catecholamines, but not with dibutyryl cAMP. This suggests that the amoeba catecholamine receptor functions downstream of the galactose lectin and upstream of adenylyl cyclase. This enteric protozoan parasite, therefore, contains the components of an autocrine catecholamine ligand-receptor system that may act in conjunction with a galactose lectin to regulate differentiation into the infectious cyst stage. PMID- 11779875 TI - Stimulation of Cl- secretion via membrane-restricted Ca2+ signaling mediated by P2Y receptors in polarized epithelia. AB - Extracellular nucleotides such as ATP have been shown to regulate ion transport processes in a variety of epithelia. This effect is mediated by the activation of plasma membrane P2Y receptors, which leads to Ca(2+) signaling cascade. Ion transport processes (e.g. activation of apical calcium-dependent Cl(-) channels) are then stimulated via an increase in [Ca(2+)](i). Many polarized epithelia express apical and/or basolateral P2Y receptors. To test whether apical and basolateral stimulation of P2Y receptors elicit polarized Ca(2+) signaling and anion secretion, we simultaneously measured the two parameters in polarized epithelia. Although activation of P2Y receptors located at both apical and basolateral membranes evoked an increase in [Ca(2+)](i), only apical P2Y receptors-coupled Ca(2+) release stimulated an increase in anion secretion. Moreover, the calcium influx evoked by apical and basolateral P2Y receptor stimulation is predominately via the basolateral membrane domain. It appears that the apical P2Y receptor-regulated Ca(2+) release and activation of apical Cl(-) channels is compartmentalized in polarized epithelia with basolateral P2Y stimulated Ca(2+) release failing to activate anion secretion. These data suggest that there may be two distinct ATP-releasable Ca(2+) pools, each coupled to apical and basolateral membrane receptor but linked to the same calcium influx pathway located at the basolateral membrane. PMID- 11779876 TI - The FXXLF motif mediates androgen receptor-specific interactions with coregulators. AB - The androgen receptor (AR) activation function 2 region of the ligand binding domain binds the LXXLL motifs of p160 coactivators weakly, engaging instead in an androgen-dependent, interdomain interaction with an FXXLF motif in the AR NH(2) terminus. Here we show that FXXLF motifs are present in previously reported AR coactivators ARA70/RFG, ARA55/Hic-5, and ARA54, which account for their selection in yeast two-hybrid screens. Mammalian two-hybrid assays, ligand dissociation rate studies, and glutathione S-transferase adsorption assays indicate androgen dependent selective interactions of these FXXLF motifs with the AR ligand binding domain. Mutagenesis of residues within activation function 2 indicates distinct but overlapping binding sites where specificity depends on sequences within and flanking the FXXLF motif. Mutagenesis of the FXXLF motifs eliminated interaction with the ligand binding domain but only modestly reduced AR coactivation in transcription assays. The studies indicate that the FXXLF binding motif is specific for the AR and mediates interactions both within the AR and with coregulatory proteins. PMID- 11779877 TI - Molecular information processing: lessons from bacterial chemotaxis. PMID- 11779879 TI - Stroke: the next 30 years. PMID- 11779880 TI - Psychological distress as a risk factor for stroke-related mortality. PMID- 11779881 TI - Does psychological distress predict the risk of ischemic stroke and transient ischemic attack? The Caerphilly Study. AB - BACKGROUND AND PURPOSE: Psychological distress is common after stroke, but little is known about its etiologic importance, although the general public often ascribes stroke to the experience of stress. Therefore, we examined whether psychological distress leads to an increased risk of ischemic stroke and transient ischemic attack (TIA). METHODS: The association between the 30-item General Health Questionnaire (GHQ), a measure of psychological distress, and the incidence of nonfatal and fatal ischemic stroke and TIA was measured by Cox regression modeling in a prospective observational study of 2201 men aged 45 to 59 years in phase II of the Caerphilly cohort. Hazard ratios comparing those with high (> or = 5) and normal GHQ scores were calculated with adjustment for age and other covariates. RESULTS: Twenty-two percent of men suffered from psychological distress, indicated by a score of > or =5 on the GHQ. There were 130 incident strokes recorded, of which 17 were fatal and 113 nonfatal. The relative risk of incident ischemic stroke was 1.45 (95% CI, 0.98 to 2.14) for those who showed symptoms of psychological distress compared with those who did not. For fatal stroke the relative risk was 3.36 (95% CI, 1.29 to 8.71) and for nonfatal stroke 1.25 (95% CI, 0.82 to 1.92). The relative risk of TIA for the distressed group was 0.63 (95% CI, 0.26 to 1.53). The results were unchanged after adjustment for body mass index, systolic blood pressure, smoking, heavy drinking, social class, and marital status. However, additionally controlling for previously diagnosed ischemic heart disease, diabetes, respiratory disease, and retirement due to ill health attenuated the relative risks, but not markedly. For fatal strokes the relative risk decreased to 2.56 (95% CI, 0.97 to 6.75) when all confounding variables were included in the model. There was a graded association between degree of psychological distress and risk of fatal ischemic stroke. CONCLUSIONS: Psychological distress is a predictor of fatal ischemic stroke but not of nonfatal ischemic stroke or TIA. Further work examining the mechanisms of this association is required. PMID- 11779882 TI - The association between trait anger and incident stroke risk: the Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND AND PURPOSE: This study examined the relation between trait anger and incident stroke risk among participants without a history of stroke at the first follow-up examination of the Atherosclerosis Risk in Communities (ARIC) study. METHODS: The study sample included 13 851 black and white men and women, aged 48 to 67 years, who completed the Spielberger Trait Anger Scale. Median follow-up time was 77.3 months. RESULTS: In the full cohort, Cox proportional hazards regression analyses showed a modest increase in the risk for stroke among individuals with high trait anger, though the association did not remain statistically significant after multivariate adjustment. Participants < or =60 years of age who reported having high trait anger had a 2.82 (95% CI, 1.65 to 4.80) times greater risk for hemorrhagic and ischemic strokes combined (any) and a 2.93 (95% CI, 1.64 to 5.22) times greater risk for ischemic strokes alone than their counterparts who reported having low trait anger (hazard rate ratios adjusted for sex and race/ethnicity). Similarly, among participants with HDL cholesterol levels >47, the risk for any stroke was 2.86 (95% CI, 1.56 to 5.25) times greater for those who reported having high trait anger, whereas the risk for ischemic strokes alone was 2.98 (95% CI, 1.58 to 5.61) times greater (hazard rate ratios adjusted for age, sex, and race/ethnicity). These associations remained strong and statistically significant after further adjustment for several established biological and sociodemographic risk factors for stroke and were absent among older participants and those with lower HDL cholesterol values. CONCLUSIONS: Trait anger was associated with an increased risk for incident stroke in the ARIC study among younger participants and those with higher HDL cholesterol levels. PMID- 11779883 TI - Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. AB - BACKGROUND AND PURPOSE: Silent brain infarcts are commonly seen on magnetic resonance imaging (MRI) both in patients with a first stroke and in healthy elderly persons. These infarcts seem associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts differ from those for symptomatic stroke. We investigated the prevalence of, and cardiovascular risk factors for, silent brain infarcts. METHODS: The Rotterdam Scan Study is a population-based cohort study among 1077 participants 60 to 90 years of age. Participants underwent cerebral MRI. We assessed cardiovascular risk factors by interview and physical examination. Associations between risk factors and presence of infarcts were analyzed by logistic regression and adjusted for age, sex, and relevant confounders. RESULTS: For 259 participants (24%) 1 or more infarcts on MRI were seen; 217 persons had only silent and 42 had symptomatic infarcts. The prevalence odds ratio (OR) of both silent and symptomatic infarcts increased with age by 8% per year (95% CI, 1.06 to 1.10 and 1.04 to 1.13, respectively). Silent infarcts were more frequent in women (age-adjusted OR, 1.4; 95% CI, 1.0 to 1.8). Hypertension was associated with silent infarcts (age- and sex-adjusted OR, 2.4; 95% CI, 1.7 to 3.3), but diabetes mellitus and smoking were not. CONCLUSIONS: Silent brain infarcts are 5 times as prevalent as symptomatic brain infarcts in the general population. Their prevalence increases with age and seems higher in women. Hypertension is associated with silent infarcts, but other cardiovascular risk factors are not. PMID- 11779884 TI - Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia Aging study. AB - BACKGROUND AND PURPOSE: Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors. METHODS: Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974. In the period from 1991 to 1993, dementia status was added to the fourth examination, and a brain MRI was completed in a fifth examination, which was from 1994 to 1996, on a subset of 575 men, who averaged 82 years. WMLs and ventricular atrophy were determined as the upper fifth in a standardized semiquantitative measure. Excess SBP variability was defined as greater than average increases in BP measurements from up to 3 examinations over 6 years. Logistic regression was used for the association of this variability with WMLs and atrophy, controlling for age, apolipoprotein E4 status, dementia diagnosis, and history of stroke. RESULTS: There were significant (2-fold) increased risks for WMLs among those with moderate and high SBP variability (third and fifth quintiles compared with the lowest quintile). Those in the highest SBP variability category (the fifth quintile) also had significantly more atrophy. CONCLUSIONS: These SBP variability MRI relationships suggest that variation in SBP in midlife may be a contributing factor to the development of WMLs and ventricular atrophy in late life. PMID- 11779886 TI - Apolipoprotein A-I and B and stroke events in a community-based cohort in Taiwan: report of the Chin-Shan Community Cardiovascular Study. AB - BACKGROUND AND PURPOSE: There are limited prospective cohort studies of the well known association between stroke events and serum lipids for the Taiwanese population, in whom stroke is the second most common cause of death. METHODS: This report describes the effect of dyslipidemia on the risk of stroke in a community-based cohort consisting of 3602 adults aged > or =35 years, established in 1990 in the Chin-Shan community in Taipei County, Taiwan. RESULTS: As of the end of 1998, 97 stroke incidence cases were identified from medical records and death certificates (53 in men and 44 in women). The female-to-male stroke event rates increased from 0.42 in the youngest group (aged 35 to 44 years) to 1.38 in the oldest (aged > or =75 years). Multiple Cox proportional hazard regression models controlling for age and sex revealed that individuals with serum apolipoprotein A-I (apoA-I) at the highest quartile were more likely to have a stroke event than those at the lowest quartile level (relative risk [RR]=2.02, P for trend=0.010). The corresponding risk of stroke predicted by apolipoprotein B (apoB) was also significant (RR=1.88, P for trend=0.020). After adjustment for age, sex, hypertension, and diabetes status, the interaction between hypertension and apoA-I level remained significant in predicting stroke events in men but not in women (RR=1.71, P=0.033 in men; RR=2.29, P=0.071 in women). CONCLUSIONS: We conclude that apoA-I but not apoB levels may serve as an effect modifier of hypertension for the risk of stroke events. PMID- 11779885 TI - Tumor necrosis factor receptor levels are associated with carotid atherosclerosis. AB - BACKGROUND AND PURPOSE: Recent evidence suggests that atherosclerosis is an inflammatory condition. Serum levels of inflammatory markers may serve as measures of the severity of atherosclerosis and risk of stroke. We sought to determine whether tumor necrosis factor-alpha (TNF-alpha) and TNF receptor levels are associated with carotid plaque thickness. METHODS: The Northern Manhattan Stroke Study is a community-based study of stroke risk factors. For this cross sectional analysis, inflammatory marker levels, including TNF-alpha and TNF receptors 1 and 2, were measured by immunoassay in stroke-free community subjects undergoing carotid duplex Doppler ultrasound. Maximal carotid plaque thickness (MCPT) was measured for each subject. Analyses were stratified by age < 70 and > or =70 years. Simple and multiple linear regression analyses were used to calculate the association between marker levels and MCPT. Multiple logistic regression was used to calculate odds ratios and 95% CIs for the association of inflammatory markers with MCPT > or =1.5 mm (>75th percentile), after adjustment for demographic and potential medical confounding factors. RESULTS: The mean age of the 279 subjects was 67.6+/-8.5 years; 49% were men; 63% were Hispanic, 17% black, and 17% white. Mean values for TNF-alpha and its receptors were as follows: TNF-alpha, 1.88+/-3.97 ng/mL; TNF receptor 1, 2.21+/-0.99 ng/mL; and TNF receptor 2, 4.85+/-2.23 ng/mL. Mean MCPT was elevated in those in the highest quartiles compared with lowest quartiles of TNF receptor 1 and 2 (1.24 versus 0.79 mm and 1.23 versus 0.80 mm, respectively). Among those aged < 70 years, TNF receptor 1 and 2 were associated with an increase in MCPT (mean difference=0.36 mm, P=0.01 for TNF receptor 1 and mean difference=0.10 mm, P=0.04 for TNF receptor 2). After adjustment for sex, race-ethnicity, hypertension, diabetes mellitus, LDL cholesterol, smoking, and body mass index, associations remained (mean difference=0.36 mm, P=0.001 for TNF receptor 1 and mean difference=0.09 mm, P=0.051 for TNF receptor 2). There was no association for TNF receptors in those aged > or = 70 years old and no association for TNF-alpha in either age group. Among those aged < 70 years, each unit increase in TNF receptor level increased the odds of the participant's having MCPT > or =1.5 mm (adjusted odds ratio=4.7; 95% CI, 1.7 to 15.4 for TNF receptor 1; odds ratio=1.9; 95% CI, 1.3 to 2.9 for TNF receptor 2). CONCLUSIONS: Relative elevation in TNF receptor levels, but not TNF-alpha, is associated with carotid atherosclerosis among individuals aged < 70 years in this multiethnic, urban population. Chronic subclinical infection or inflammation may account for this association, and modification of these inflammatory pathways may provide a novel approach to stroke prevention. PMID- 11779887 TI - Leukoaraiosis, ischemic stroke, and normal white matter on diffusion-weighted MRI. AB - BACKGROUND AND PURPOSE: Leukoaraiosis is a radiological finding of uncertain pathogenesis with bilateral patchy or diffuse areas of hyperintensity of the cerebral white matter (WM) on T2-weighted MRI. Using diffusion-weighted MRI (DWI), we aimed to test (1) whether the average apparent diffusion coefficient (ADC(av)) values of the regions of leukoaraiosis vary according to the degree of the severity of leukoaraiosis and whether the regions of leukoaraiosis could be distinguished (2) from normal WM or (3) from ischemic strokes of various ages. METHODS: We compared 85 patients with leukoaraiosis, 22 healthy subjects with no leukoaraiosis on the conventional MR images, and 10 patients with ischemic strokes serially imaged <6 hours, 24 hours, 1 week, 1 month, and 3 months after stroke onset. All subjects were studied with DWI in 3 orthogonal directions with 2 b values (b=0 and b=1000 s/mm(2)) at 1.5 T. ADC(av) values were determined for the regions of leukoaraiosis, ischemic lesions, and normal WM. RESULTS: The more severe the leukoaraiosis was, the higher the ADC(av) values of the leukoaraiotic regions became. The ADC(av) values (in 10(-3) mm(2)/s) of the regions of leukoaraiosis (0.92 to 1.27) were significantly higher than that of the normal WM (0.69+/-0.04) and that of the ischemic strokes at 6 hours (0.38+/-0.07), 24 hours (0.36+/-0.10), and 1 week (0.51+/-0.09). One-month-old ischemic strokes (1.08+/ 0.33) had ADC(av) values similar to those of leukoaraiotic regions, whereas 3 month-old infarcts (1.59+/-0.32) showed significantly higher ADC(av) values than the leukoaraiotic regions. CONCLUSIONS: The regions of leukoaraiosis show characteristic changes in ADC(av) values, and DWI can be used to differentiate acute and chronic ischemic stroke lesions from leukoaraiosis. PMID- 11779888 TI - Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke. AB - BACKGROUND AND PURPOSE: The mechanisms of ischemic stroke in young adults are poorly understood. During the last years, several studies suggested a role for genetic factors predisposing to thrombophilia and for moderate hyperhomocysteinemia in this setting. METHODS: We evaluated in 132 consecutive patients (66 males, 66 females; mean+/-SD age, 38.4+/-11.7 years; mean+/-SD age at first event, 34.8+/-10.9 years; range, 6 months to 50 years) referred to our center between January 1997 and December 1999 for a history of young adult ischemic stroke (age at first event, <51 years) the prevalence of factor V (FV) Leiden, prothrombin (FII) G20210A, and C677T and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene mutations and fasting serum total homocysteine levels. Two hundred sixty-two apparently healthy subjects (117 males, 145 females; mean+/-SD age, 36+/-13.2 years) served as controls. RESULTS: Total homocysteine levels differed significantly (P=0.004, t test) between patients and controls: 13.03+/ 18.61 versus 10.75+/-6.24 micromol/L (mean+/-SD), respectively. In contrast, homozygosity for the TT mutation of the MTHFR gene was 30 of 132 (22.7%) in patients and 45 of 262 (17.2%) in controls; this difference was not statistically significant (P>0.05, chi(2) test). However, when we stratified the whole population according to genotype, fasting serum homocysteine levels were significantly higher in TT patients than in TT controls (25.3+/-36.8 versus 15+/ 11.6 micromol/L; P=0.02, t test). Mutations of FV Leiden and of FII G20210A gene are currently reported to be associated with a tendency toward ischemic stroke. Their frequencies were not statistically significantly different between patients and controls in this setting: 7 of 132 (5.3%) versus 17 of 262 (6.5%) for FV Leiden and 10 of 132 (7.6%) versus 16 of 262 (6.1%) for FII G20210A, respectively (all P>0.05, chi(2) test). CONCLUSIONS: In the present cohort of patients, moderate hyperhomocysteinemia is the only variable that helps to identify young adults with a history of ischemic stroke. PMID- 11779889 TI - Aspirin and urinary 11-dehydrothromboxane B(2) in African American stroke patients. AB - BACKGROUND AND PURPOSE: The aim of the study was to evaluate the relationship between daily aspirin use and urinary excretion of a stable thromboxane metabolite, 11-dehydrothromboxane B(2) (11-DTB2), in African American stroke patients. METHODS: Subjects were a subgroup of those screened for the African American Antiplatelet Stroke Prevention Study. Subjects were within 4 months of noncardioembolic ischemic stroke and were not being treated with anticoagulants. Antithrombotic therapy at the time of urine collection varied according to the practice patterns of various attending physicians who treated the patients during their acute strokes. 11-DTB2 was measured by enzyme immunoassay in random urine samples 1 to 4 months after the stroke. RESULTS: Eighty-seven of 92 patients enrolled were able to give a urine sample at the time of enrollment. There were 51 men and 36 women aged 36 to 87 (mean 62) years. On the basis of antithrombotic treatment before the sample collection, we divided patients into 4 groups: (1) 16 patients treated with no aspirin (no antithrombotic drugs [n=4] or ticlopidine [n=12]), (2) 21 patients treated with 81 to 325 mg aspirin per day (81 mg/d [n=2], 325 mg/d [n=19]), (3) 20 patients treated with 650 mg aspirin per day, and (4) 30 patients treated with 975 to 1300 mg aspirin per day (975 mg/d [n=2] and 1300 mg/d [n=28]). In patients taking daily aspirin at any dose, the median urinary 11-DTB2 was 783 pg/mg creatinine compared with 1386 pg/mg creatinine in patients not taking daily aspirin (P=0.01 by Wilcoxon rank sum test). In multivariate regression analysis, aspirin use remained significantly associated with lower urinary 11-DTB2 (P=0.008). There was no dose-response effect between the 3 aspirin dose groups and urinary 11-DTB2 (P=0.70). CONCLUSIONS: In African American stroke patients, aspirin use is associated with significantly lower urinary 11-DTB2 independent of other vascular factors, and there does not appear to be a dose-response effect for aspirin doses of 325 to 1300 mg daily. The clinical significance of these finding remains to be determined. PMID- 11779890 TI - Changes of neural activity correlate with the severity of cortical ischemia in patients with unilateral major cerebral artery occlusion. AB - BACKGROUND AND PURPOSE: In major cerebral arterial steno-occlusive diseases, there can be remarkably decreased hemodynamic reserve without marked neurological impairments. In such settings, it is not known whether the neural activity is well maintained or disturbed according to the severity of cerebral ischemia. The present study was therefore undertaken to examine the neural activity under mild cerebral ischemia resulting from major cerebral arterial occlusion. METHODS: Seven patients with minor neurological impairment as well as either unilateral internal carotid artery or middle cerebral artery occlusion were studied. The severity of the cortical ischemia was assessed by measuring regional cerebral blood flow (rCBF) with positron emission tomography. The change in neural activity in the ischemic brain was then evaluated by means of somatosensory evoked magnetic field with magnetoencephalography. RESULTS: The rCBF in the primary sensory area and the strength of the initial component of somatosensory evoked magnetic field (N20 m) were significantly reduced (P<0.01) and the second component (P30 m) was significantly augmented (P<0.05) in the lesioned cerebral hemisphere as compared with the nonlesioned hemisphere. The asymmetry indexes for N20 m were positively correlated (r=0.78) and those for P30 m were inversely correlated (r=-0.92) with asymmetry indexes for rCBF. CONCLUSIONS: In patients with either unilateral internal carotid artery or middle cerebral artery occlusion and minor neural impairments, there was a reduction of afferent signal and an augmentation of the secondary response of the neurons in the primary sensory area. This showed correlation with the severity of cortical ischemia. PMID- 11779891 TI - Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. AB - BACKGROUND AND PURPOSE: An increased frequency of clinically silent microbleeds (MB) has recently been observed in patients with sporadic small-vessel disease related to vascular amyloid deposition or hypertension. In this study, we searched for cerebral MBs in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a unique type of small vessel disease caused by mutations in the Notch3 gene. Our purposes were (1) to determine the frequency, extent, and pattern of MBs in CADASIL; (2) to analyze the relationship between MBs and T2-hyperintense lesions; and (3) to evaluate the histopathology of brain tissue affected by MBs. METHODS: Gradient-echo, T2/PD weighted dual-echo, and T1-weighted MRI scans of the brain were obtained from 16 consecutive CADASIL subjects and 16 age-matched control subjects. T2-lesion volume measurements were made with a semiautomated segmentation technique based on local thresholding. Postmortem examinations were performed on the brains of 7 additional CADASIL subjects. RESULTS: Focal areas of signal loss on gradient-echo images suggesting past MBs were found in 11 CADASIL individuals (69%) and no control subjects (P<0.001). The average number of MBs was 5.9+/-7.3 (range, 0 to 22) in individual CADASIL patients. MBs were associated with age (r=0.71, P=0.002) and total lesion volume (r=0.75, P=0.001). However, after correction for age, the correlation with lesion volume was no longer significant. MBs were located simultaneously in various parts of the brain with a preference for cortical-subcortical regions (38%), white matter (20%), thalamus (13%), and brainstem (14%). Eighty-two percent of the MBs were located outside areas appearing hyperintense on T2-weighted images. Postmortem examination revealed focal accumulations of hemosiderin-containing macrophages in 6 of the 7 brains (86%). They were always found outside ischemic lesions. CONCLUSIONS: This study shows a high frequency and multiplicity of MBs in individuals with CADASIL. Our results suggest that MBs and ischemic lesions are largely independent manifestations of the underlying angiopathy. The pattern of MBs shows a significant overlap with that reported in other types of small-vessel disease. PMID- 11779892 TI - Basilar vasospasm diagnosis: investigation of a modified "Lindegaard Index" based on imaging studies and blood velocity measurements of the basilar artery. AB - BACKGROUND AND PURPOSE: Numerous studies have shown that cerebral vasospasm is one of the leading causes of death and neurological disability after subarachnoid hemorrhage. Most of these studies, however, have focused on anterior circulation vessels. Since the introduction of the transcranial Doppler (TCD), increasing attention has been given to basilar artery (BA) vasospasm, especially in traumatic subarachnoid hemorrhage. As shown for the anterior circulation, however, the significance of elevated flow velocities (FVs) in the posterior vessels may be ambiguous, so vasospasm may not be reliably differentiated from hyperemia. The purpose of the present study was to evaluate the potential additional value of an intracranial/extracranial FV ratio in the posterior circulation to cope with this shortcoming of the TCD in the diagnosis of BA vasospasm. METHODS: FV in the extracranial vertebral artery (VA) was measured in 20 healthy volunteers. Normative values of an intracranial/extracranial VA FV ratio (IVA/EVA) and a BA/extracranial VA FV ratio (BA/EVA) were calculated. Thirty-four patients with subarachnoid hemorrhage were then evaluated with TCD and CT angiography (CTA). The value of the IVA/EVA and BA/EVA ratios in the diagnosis and assessment of vertebrobasilar vasospasm was investigated. RESULTS: The extracranial VA could be insonated in all subjects at depths ranging from 45 to 55 mm. The average FV for the extracranial VA was 26 cm/s. The ratios between intracranial and extracranial VA FVs were 1.6 on both sides, whereas the ratio between the BA FVs and the mean extracranial VA FVs was slightly higher at 1.7. Fourteen patients (41.2%) had CTA evidence of BA vasospasm. Vasospasm was severe in 7 patients, moderate in 1, and mild in the remaining. An FV threshold of 80 cm/s was indicative of BA vasospasm in 92.8% with 3 false-positive results that could be related to vertebrobasilar hyperemia. Comparative analysis between CTA and TCD findings showed that BA/EVA was >2 in all patients with BA vasospasm (100% sensitivity) and < 2 in all but 1 patient without BA vasospasm (95% specificity). Furthermore, the BA/EVA ratio showed a close correlation with BA diameter (r=-0.8139, P<0.0001) and was >3 in all patients with severe vasospasm. CONCLUSIONS: The results of the present study showed that the BA/EVA ratio may contribute to an improved discrimination between BA vasospasm and vertebrobasilar hyperemia and enhance the accuracy and reliability of TCD in the diagnosis of BA vasospasm. Our data further suggest that the BA/EVA ratio may provide an approximation of vasospasm severity and help in identifying patients who are likely to suffer from hemodynamically significant vasospasm. PMID- 11779893 TI - Severe ADC decreases do not predict irreversible tissue damage in humans. AB - BACKGROUND AND PURPOSE: A mismatch between diffusion- and perfusion-weighted MRI is thought to define tissue at risk of infarction. This concept is based on the assumption that diffusion slowing of and decreases in the apparent diffusion coefficient (ADC) serve as indicator of tissue proceeding to infarction. We tested this hypothesis. METHODS: MRI (diffusion weighted, perfusion weighted, MRA, T2 weighted) was performed in 15 patients with acute stroke within 2.9+/-0.8 hours (mean+/-SD) of onset and on days 1 and 7. After intraindividual realignment of the ADC maps, the development of ADC range volumes and ADC values was determined. RESULTS: An increase (354%, group A1) in the total ADC-based lesion volume below a threshold of < 80% occurred in 4 patients on day 1, persisting on day 7 with a pronounced increase of ADC range volumes with low ADC values. An increase in total ADC-based lesion volume (201%, group A2) followed by a secondary drop to day 7 was found in 7 patients. A significant reduction in total ADC-based lesion volume (14%, group B) was found in 4 patients. ADC-based lesion volume increase was associated with persistent vessel occlusion in group A, whereas recanalization in group B resulted in ADC volume decrease. ADC normalization was observed independently from the degree of the initial ADC decrease on days 1 and 7 in group B. CONCLUSIONS: In line with results from animal experiments, ADC decreases do not reliably indicate tissue infarction Even severely decreased ADC values may normalize in human stroke, and it seems likely that ADC normalization depends on the duration and severity of ischemia rather than the absolute value. PMID- 11779894 TI - Magnetic resonance perfusion-weighted imaging of acute cerebral infarction: effect of the calculation methods and underlying vasculopathy. AB - BACKGROUND AND PURPOSE: Various calculation methods are available to estimate the transit-time on MR perfusion-weighted imaging (PWI). Each method may affect the results of PWI. Steno-occlusive disease in the parent vessels is another factor that may affect the results of the PWI. The purpose of this study was to elucidate the effect of the calculation methods and underlying vasculopathy on PWI. METHODS: From a pool of 113 patients who had undergone PWI during the study period, a total of 12 patients with nonlacunar ischemic strokes who were scanned within 24 hours after onset of symptom were selected for the study. The patient population consisted of 6 patients who had extracranial internal carotid artery stenosis (>70%) and 6 individuals without stenosis. Seven different postprocessing methods were evaluated: first moment, ratio of area to peak, time to peak (TTP), relative TTP, arrival time, full-width at half-maximum, and deconvolution methods. Follow-up MR or CT images were used to determine the areas that evolved into infarcts, which served as the gold standard. Sensitivity and specificity of each transit time technique were calculated. RESULTS: Calculation methods with high sensitivity were the first moment (sensitivity, 74%), TTP (sensitivity, 77%), and deconvolution methods (sensitivity, 81% to 94%). Between the 2 groups with and without internal carotid artery stenosis, the specificity of most of the techniques was lower in the internal carotid artery stenosis group. The first moment and deconvolution methods maintained relatively high specificity even in the stenosis group. CONCLUSIONS: The calculation technique and presence of underlying vasculopathy have a direct impact on the results of PWI. The methods with high sensitivity even in the presence of steno-occlusive disease were the first moment and deconvolution methods with arterial input function derived from the peri-infarct arteries; the deconvolution method was the superior choice because of higher lesion conspicuity. PMID- 11779895 TI - Magnetic resonance imaging detection of microbleeds before thrombolysis: an emerging application. AB - BACKGROUND: Hemorrhagic transformation (HT) is a major complication of thrombolytic treatment for acute ischemic stroke. Although a history of prior intracerebral hemorrhage diagnosed by head CT is a contraindication to thrombolysis, there are no guidelines or data regarding evidence of prior asymptomatic microbleeds visualized with T2*-weighted magnetic resonance imaging (MRI). METHODS: Pretreatment T2*-weighted MRI sequences were retrospectively analyzed in all patients receiving intra-arterial thrombolytic therapy and undergoing a pretreatment MRI at our institution. The frequency and location of prior microbleeds was determined and compared with the frequency and location of secondary HT after therapy. RESULTS: Five of 41 patients undergoing MRI before receiving intra-arterial thrombolytic therapy demonstrated evidence of prior microbleeds on the pretreatment MRI studies. Major symptomatic hemorrhage occurred in 1 of 5 patients with microbleeds compared with 4 of 36 patients without. Only 1 patient in the entire 41-patient cohort experienced any HT outside the acute ischemic field. In this patient, the symptomatic hemorrhage occurred directly at the site of a prior microbleed, contralateral to the acute ischemic event. CONCLUSIONS: Old silent microbleeds, visualized with T2*-weighted MRI sequences, may be a marker of increased risk of HT in patients receiving thrombolytic therapy for acute ischemic stroke. Pretreatment screening of thrombolytic candidates with these MRI sequences may be useful in the future to identify these patients. PMID- 11779896 TI - Clinical and sonographic patterns of tandem internal carotid artery/middle cerebral artery occlusion in tissue plasminogen activator-treated patients. AB - BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) is predictive of thrombus presence but has limited ability to identify occlusion location in the anterior circulation. We describe clinical and sonographic patterns that are associated with tandem internal carotid artery (ICA) and middle cerebral artery (MCA) occlusions. METHODS: Consecutive acute ischemic stroke patients receiving intravenous tissue plasminogen activator (TPA) were studied. Pretreatment NIHSS scores and bedside transcranial Doppler (TCD) were obtained for all patients. RESULTS: A total of 95 patients treated with intravenous TPA at 132+/-60 minutes from stroke onset were studied. On TCD, 48 had isolated MCA occlusion (mean NIHSS 16.8+/-5.8, median 17, range 5 to 28); and 16 had tandem ICA/MCA occlusion (mean NIHSS 18.8+/-5.8, median 22, range 8 to 29; P=NS). In the MCA occlusion and tandem ICA/MCA occlusion groups, 19% and 11%, respectively, had NIHSS scores <12 points. Compared with the NIHSS scores in patients with hemiplegia, forced gaze deviation, and complete neglect, the lower NIHSS scores were attributable to partial arm and/or leg paresis, gaze preference, and partial neglect. In those patients, TCD showed > or =2 major collateral channels and low resistance flow at the M1 origin, suggesting perfusion of perforating arteries. Although TCD cannot differentiate between high-grade ICA stenosis or occlusion, collateral flow patterns and stenotic signals at the terminal ICA differentiated tandem lesions from isolated MCA occlusion (P<0.01). CONCLUSIONS: Tandem ICA/MCA occlusion was found on TCD in 17% of TPA-treated patients. NIHSS scores were similar in patients with isolated MCA and tandem occlusions. Lower NIHSS scores were seen in patients with a higher number of major collateral flow channels and higher Thrombolysis in Brain Ischemia (TIBI) flow grades at the MCA origin. PMID- 11779897 TI - Altered hemodynamic responses in patients after subcortical stroke measured by functional MRI. AB - BACKGROUND AND PURPOSE: Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) is a promising method for defining brain recovery after stroke quantitatively. Applications thus far have assumed that the BOLD hemodynamic response in patients after stroke is identical to that in healthy controls. However, because of local vascular compromise or more diffuse vascular disease predisposing to infarction, this assumption may not be justified after stroke. We sought to test whether patients who have suffered a lacunar stroke show BOLD fMRI response characteristics identical to those of healthy controls. METHODS: We measured the BOLD fMRI signal time course in the sensorimotor cortex contralateral to the affected hand with finger- or hand-tapping tasks for minimally or mildly impaired right-handed patients (n=12) after lacunar strokes causing limb weakness and for healthy controls (n=20). RESULTS: With a right handed sequential finger-tapping task, the rate of rise and maximum increase of the BOLD signal in the contralateral sensorimotor cortex were > 30% lower (P< or =0.01) in the stroke patients. Similar relative decreases were found for the same task performed with the left hand. These changes were found in patients both in the hemisphere affected by stroke and in the unaffected hemisphere, suggesting that the BOLD fMRI time course differences observed arise from a diffuse functional pathology. The difference between patients and controls is not a result of age alone, since differences were not found between the younger (n=10; aged 22 to 38 years) and the older (n=10; aged 56 to 83 years) healthy controls. The effect also does not seem to be dependent on the specific hand movement task used. CONCLUSIONS: The magnitude of the BOLD fMRI response can be reduced in stroke patients even if infarcts do not involve the cortex. This may be a consequence of the stroke, but the observation that the BOLD signal time course is similar in the affected and unaffected hemispheres suggests that it also could result from preexisting pathophysiological changes in the cerebral microvasculature. PMID- 11779898 TI - Hemodynamic and metabolic changes in transient ischemic attack patients: a magnetic resonance angiography and (1)H-magnetic resonance spectroscopy study performed within 3 days of onset of a transient ischemic attack. AB - BACKGROUND AND PURPOSE: We investigated whether patients with transient ischemic attack (TIA) have systemic low flow to the brain or an abnormal intracranial flow distribution caused by an abnormal anatomy of the circle of Willis. Furthermore, we investigated whether metabolic changes were present in the brain. METHODS: Forty-four patients with clinically diagnosed TIA were prospectively included in our study. Clinical and neurological data were compiled. MR imaging; quantitative flow measurements of the internal carotid, middle cerebral, and basilar arteries; MR angiography of the circle of Willis; and (1)H-MR spectroscopy were performed in all patients within 3 days of onset of symptoms. RESULTS: Compared with control subjects, TIA patients did not have altered flow volume in any of the arteries and had normal flow distribution through the circle of Willis. In TIA patients, the N-acetylaspartate (NAA)/choline ratio in noninfarcted regions was significantly decreased in the symptomatic hemisphere (1.73+/-0.16) compared with the asymptomatic hemisphere (1.84+/-0.19, P<0.05) and control subjects (1.90+/ 0.17, P<0.001). In the symptomatic hemisphere, the lactate/NAA ratio was significantly increased (0.04+/-0.08) compared with control subjects (0.00+/ 0.01, P<0.05). Patients with a history of prior TIA had a significantly decreased NAA/choline ratio in both the symptomatic (P<0.05) and asymptomatic (P<0.05) hemispheres compared with TIA patients without a prior TIA. CONCLUSIONS: TIA patients have neurological deficits that are transient; however, metabolic damage to the brain is present up to 3 days after the onset of the symptoms. These metabolic changes are not restricted to the symptomatic hemisphere or to areas close to ischemic lesions. PMID- 11779899 TI - Selective vulnerability of the lumbosacral spinal cord after cardiac arrest and hypotension. AB - BACKGROUND AND PURPOSE: It is generally accepted that the gray matter in the watershed area of the midthoracic level of the spinal cord is the ischemic watershed zone of the spinal cord. We performed a retrospective study to reevaluate the frequency and distribution of spinal cord injury after a global ischemic event. METHODS: Clinical files and neuropathology specimens of all adult patients with either a well-documented cardiac arrest or a severe hypotensive episode, as well as pathologically confirmed ischemic encephalopathy and/or myelopathy, were reviewed by an independent reviewer. RESULTS: Among 145 cases satisfying selection criteria, ischemic myelopathy was found in 46% of patients dying after either a cardiac arrest or a severe hypotensive episode. Among the patients with myelopathy, predominant involvement of the lumbosacral level with relative sparing of thoracic levels was observed in >95% of cardiac arrest and hypotensive patients. None of the examined patients developed neuronal necrosis limited to the thoracic level only. CONCLUSIONS: Our findings indicate a greater vulnerability of neurons in the lumbar or lumbosacral spinal cord to ischemia than other levels of the spinal cord. PMID- 11779900 TI - Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results. AB - BACKGROUND AND PURPOSE: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study. METHODS: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure. RESULTS: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug. CONCLUSIONS: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke. PMID- 11779901 TI - Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. AB - BACKGROUND AND PURPOSE: Mild alterations in temperature have prominent effects on ischemic cell injury and stroke outcome. Elevated core body temperature (CBT), even if mild, may exacerbate neuronal injury and worsen outcome, whereas hypothermia is potentially neuroprotective. The antipyretic effects of acetaminophen were hypothesized to reduce CBT. METHODS: This was a randomized, controlled clinical trial at 2 university hospitals. Patients were included if they had stroke within 24 hours of onset of symptoms, National Institutes of Health Stroke Scale (NIHSS) score > or =5, initial CBT <3 8.5 degrees C, and white blood cell count < 12 600 cells/mm(3); they were excluded if they had signs of infection, severe medical illness, or contraindication to acetaminophen. CBT was measured every 30 minutes. Patients were randomized to receive acetaminophen 650 mg or placebo every 4 hours for 24 hours. The primary outcome measure was mean CBT during the 24-hour study period; the secondary outcome measure was the change in NIHSS. RESULTS: Thirty-nine patients were randomized. Baseline CBT was the same: 36.96 degrees C for acetaminophen versus 36.95 degrees C for placebo (P=0.96). During the study period, CBT tended to be lower in the acetaminophen group (37.13 degrees C versus 37.35 degrees C), a difference of 0.22 degrees C (95% CI, -0.08 degrees C to 0.51 degrees C; P=0.14). Patients given acetaminophen tended to be more often hypothermic <36.5 degrees C (OR, 3.4; 95% CI, 0.83 to 14.2; P=0.09) and less often hyperthermic >37.5 degrees C (OR, 0.52; 95% CI, 0.19 to 1.44; P=0.22). The change in NIHSS scores from baseline to 48 hours did not differ between the groups (P=0.93). CONCLUSIONS: Early administration of acetaminophen (3900 mg/d) to afebrile patients with acute stroke may result in a small reduction in CBT. Acetaminophen may also modestly promote hypothermia <36.5 degrees C or prevent hyperthermia >37.5 degrees C. These effects are unlikely to have robust clinical impact, and alternative or additional methods are needed to achieve effective thermoregulation in stroke patients. PMID- 11779902 TI - Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. AB - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the effects of hypertonic saline in stroke patients with increased intracranial pressure (ICP) after conventional therapy with mannitol had failed. METHODS: Twenty-two episodes of ICP crisis occurred in 8 patients in whom the standard treatment of 200 mL of 20% mannitol was not effective. ICP crisis was defined as an increase in ICP of 20 mm Hg (n=18), pupillary abnormality (n=3), or a combination of both (n=1). The patients were treated with 75 mL of 10% saline over the course of 15 minutes. ICP, mean arterial blood pressure, and cerebral perfusion pressure were monitored for 4 hours. Blood gases, hematocrit, hemoglobin, pH, osmolarity, and electrolytes levels were measured before and 15 and 60 minutes after the start of infusion. Treatment was regarded as effective if ICP decreased >10% or the pupillary reaction had normalized. RESULTS: Treatment was effective in all 22 episodes. The maximum ICP decrease was 9.9 mm Hg 35 minutes after the start of infusion. Thereafter, ICP began to rise again. There was no constant effect on mean arterial blood pressure, whereas cerebral perfusion pressure was consistently increased. Blood osmolarity rose by 9 mmol/L and serum sodium by 5.6 mmol/L. Potassium levels, hemoglobin, hematocrit, and pH were slightly decreased. No unexpected side effects were noted. CONCLUSIONS: Infusion of 75 mL hypertonic (10%) saline decreases elevated ICP and increases cerebral perfusion pressure in stroke patients in whom mannitol had failed. The effect on the ICP and cerebral perfusion pressure reaches its maximum after the end of infusion and is seen for 4 hours. PMID- 11779903 TI - Extending tissue plasminogen activator use to community and rural stroke patients. AB - BACKGROUND AND PURPOSE: Guidelines for intravenous tissue plasminogen activator (tPA) use in stroke emphasize the importance of limiting its use to facilities with imaging capabilities and stroke expertise. This prospective case series set out to evaluate the safety of tPA use in patients referred from rural communities to a tertiary center. METHODS: Prospective data of 82 consecutive patients treated with tPA in London, Ontario, were reviewed. RESULTS: Twenty-three patients were transferred to London from a rural hospital (non-London patients); 49 were first evaluated in a London emergency room (London ER); and 10 were inpatients in a London hospital at the time of stroke onset. Mean transfer time and distance to London for non-London patients were 89 minutes and 41 miles. Although symptom onset to London ER times were longer for non-London than for London ER patients (123 versus 53 minutes), the door to needle times were significantly shorter for the former (49 versus 95 minutes, P<0.005). Imaging to needle times were longer for London inpatients compared with London ER patients (55 versus 36 minutes, P=0.16). The proportion of patients with >4-point improvement on the NIH Stroke Scale or cure at 24 hours was 57%, with no difference among groups (P=0.46). The overall symptomatic hemorrhage rate at 36 hours was 2%. No significant differences in outcomes were observed at 3 months. CONCLUSIONS: This prospective study suggests that it is feasible and safe to treat rural patients referred to a tertiary care center with tPA, thus extending the benefits of thrombolysis for acute stroke to a wider population. PMID- 11779904 TI - The nonpeptide glycoprotein IIb/IIIa platelet receptor antagonist SM-20302 reduces tissue plasminogen activator-induced intracerebral hemorrhage after thromboembolic stroke. AB - BACKGROUND AND PURPOSE: Platelet activation and deposition in brain microvessels appear to be key events in the pathogenesis of ischemia-induced neuronal degeneration and behavioral deficits. It has been hypothesized that activated platelets in combination with polymorphonuclear leukocytes and fibrin may play a role in vessel reocclusion leading to the "no-reflow" phenomenon after administration of the thrombolytic tissue plasminogen activator (tPA). We studied the effects of the novel glycoprotein IIb/IIIa platelet receptor antagonist SM 20302 when administered in combination with tPA on infarct and hemorrhage rate and volume to determine whether activated platelets are involved in either infarct or hemorrhage generation after a thromboembolic stroke. METHODS: One hundred thirty-two male New Zealand White rabbits were included in the present study. Rabbits were embolized by injecting a blood clot into the middle cerebral artery via a catheter. Five or 65 minutes after embolization, SM-20302 (5 mg/kg) was infused intravenously. In drug combination studies, tPA was infused intravenously for 30 minutes starting 60 minutes after embolization, and SM-20302 was administered 5 or 65 minutes after embolization. Postmortem analysis included assessment of hemorrhage, infarct size and location, and clot lysis. RESULTS: In the vehicle control group, the hemorrhage rate after a thromboembolic stroke was 33%. There was a significant increase (109%) in the hemorrhage rate in the group of rabbits treated with the thrombolytic tPA. SM-20302 by itself did not significantly alter the embolism-induced hemorrhage rate when administered either 5 or 65 minutes after embolism. The SM-20302 groups had a 42% and 33% incidence of hemorrhage in the 5- and 65-minute groups, respectively. In groups treated with a combination of drugs, the SM-20302/tPA group had a 31% and 71% incidence of hemorrhage when SM-20302 was administered 5 and 65 minutes after embolization, respectively. SM-20302 in combination with tPA also significantly increased infarct rate, but not hemorrhage or infarct volume. CONCLUSIONS: This study suggests that treatment of thromboembolic stroke with the combination of a platelet inhibitor and tPA may have a beneficial outcome on the basis of the following: First, acute administration of SM-20302 did not significantly increase hemorrhage rate. Second, SM-20302 in combination with tPA significantly reduced tPA-induced intracerebral hemorrhage. Third, there appears to be a specific window of opportunity when a platelet inhibitor must be administered to produce a beneficial effect. Overall, on the basis of our results, we hypothesize that the increased rate of intracerebral hemorrhage observed after tPA administration may be partly due to increased reocclusion of cerebral vessels following lysis of the emboli and that reocclusion can be controlled by administration of a platelet inhibitor. PMID- 11779905 TI - Factors influencing early admission in a French stroke unit. AB - BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator improves outcome after ischemic stroke when given within 3 hours of symptoms onset in carefully selected patients. However, only a small proportion of acute stroke patients are currently eligible for thrombolysis, mainly because of excessive delay to hospital presentation. We sought to determine the factors associated with early admission in a French stroke unit. METHODS: We prospectively studied the admission delay of acute stroke patients in a French stroke unit during a 12 month period ending July 1999. Univariate and multivariate regression analyses were performed to evaluate the factors influencing early stroke unit admission and transport by the Emergency Medical Services (EMS) or Fire Department (FD) ambulances. RESULTS: One hundred sixty-six patients were primarily admitted to the stroke unit, with a median admission time of 4 hours 5 minutes. Twenty-nine percent presented within 3 hours of symptoms onset and 75% within 6 hours. Univariate analysis showed that early stroke unit arrival was significantly associated with the following factors: female sex, stroke severity assessed by the National Institutes of Health Stroke Scale score, lowered consciousness, sudden onset of stroke, not living alone, recognition of symptoms by bystanders, and transport by EMS or FD ambulances. Age, ethnicity, level of education, employment status, nocturnal onset, distance from place of stroke to the stroke unit, stroke lesion location, presence of brain hemorrhage, and awareness about the symptoms and risk factors of stroke had no measurable effect on early admission. A multivariate regression model demonstrated that the most significant factors associated with early stroke unit arrival were transport by EMS or FD ambulances and sudden onset of stroke. Female sex and not living alone were also significantly associated with early admission in the multivariate model. Multivariate analysis of the mode of transport showed that transport by EMS or FD ambulances was significantly more frequent among female patients, when stroke symptoms were recognized by bystanders, and when the general practitioner was not the first medical contact. CONCLUSIONS: The present study shows that hospital arrival within the first hours of stroke is feasible in a French stroke unit. As many as 75% of the patients are admitted within the first 6 hours of stroke. This is the first study demonstrating that stroke unit admission in France is fastest in patients brought to the hospital by EMS or FD ambulances. However, only 35% of stroke patients activate the emergency telephone system and are currently transported by EMS or FD ambulances. French stroke patients should be encouraged to seek immediate medical attention by using the emergency telephone system, and stroke management should be reprioritized in the French EMS as a time-dependent medical emergency, with the same level of organization and expertise currently applied to myocardial infarction. PMID- 11779906 TI - Improving delivery of acute stroke therapy: The TLL Temple Foundation Stroke Project. AB - BACKGROUND AND PURPOSE: Only a small minority of acute stroke patients receive approved acute stroke therapy. We performed a community and professional behavioral intervention project to increase the proportion of stroke patients treated with approved acute stroke therapy. METHODS: This study used a quasi experimental design. Intervention and comparison communities were compared at baseline and during educational intervention. The communities were based in 5 nonurban East Texas counties. The multilevel intervention worked with hospitals and community physicians while changing the stroke identification skills, outcome expectations, and social norms of community residents. The primary goal was to increase the proportion of patients treated with intravenous recombinant tissue plasminogen activator (rTPA) from 1% to 6% of all cerebrovascular events in the intervention community. RESULTS: We prospectively evaluated 1733 patients and validated 1189 cerebrovascular events. Intravenous rTPA treatment increased from 1.38% to 5.75% among all cerebrovascular event patients in the intervention community (P=0.01) compared with a change from 0.49% to 0.55% in the comparison community (P=1.00). Among the ischemic stroke patients, an increase from 2.21% to 8.65% was noted in the intervention community (P=0.02). The comparison group did not appreciably change (0.71% to 0.86%, P=1.00). Of eligible intravenous rTPA candidates, treatment increased in the intervention community from 14% to 52% (P=0.003) and was unchanged in the comparison community (7% to 6%, P=1.00). CONCLUSIONS: An aggressive, multilevel stroke educational intervention program can increase delivery of acute stroke therapy. This may have important public health implications for reducing disability on a national level. PMID- 11779907 TI - Adherence to postacute rehabilitation guidelines is associated with functional recovery in stroke. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine if compliance with poststroke rehabilitation guidelines was associated with better functional outcomes. METHODS: An inception cohort of 288 stroke patients in 11 Department of Veteran Affairs Medical Centers hospitalized between January 1998 and March 1999 were followed prospectively for 6 months. Data were abstracted from medical records and telephone interviews. The primary study outcome was the Functional Independence Motor Score (FIM). Secondary outcomes included Instrumental Activities of Daily Living (IADL), SF-36 physical functioning, and the Stroke Impact Scale (SIS). Acute and postacute rehabilitation guideline compliance scores (range 0 to 100) were derived from an algorithm. All outcomes were adjusted for case-mix. RESULTS: Average compliance scores in acute and postacute care settings were 68.2% (SD 14) and 69.5% (SD 14.4), respectively. After case mix adjustment, level of compliance with postacute rehabilitation guidelines was significantly associated with FIM motor, IADL, and the SIS physical domain scores. SF-36 physical function was not associated with guideline compliance. Level of compliance with rehabilitation guidelines in acute settings was unrelated to any of the outcome measures. CONCLUSION: Greater levels of adherence to postacute stroke rehabilitation guidelines were associated with improved patient outcomes. Compliance with guidelines may be viewed as a quality-of-care indicator with which to evaluate new organizational and funding changes involving postacute stroke rehabilitation. PMID- 11779908 TI - Effect of age on functional outcomes after stroke rehabilitation. AB - BACKGROUND AND PURPOSE: The incidence of stroke and the demand for stroke rehabilitation services continues to increase, and it has been proposed that age be used in combination with severity of stroke to determine type of rehabilitation. It is important to identify the impact of age on functional outcome before embracing a system that limits access to rehabilitation on the basis of age. METHODS: This prospective study includes all patients admitted to an inpatient stroke rehabilitation program for 6 years. Demographic and clinical data were extracted by means of chart review. Functional status at admission and discharge was evaluated by means of the FIM instrument. Multivariate regression techniques were used to assess the relationships between age, functional outcome, and other predictive variables. Particular attention was paid to the r(2) values to assess the amount of variation accounted for by the predictors. RESULTS: Age alone was a significant predictor of total FIM score and Motor FIM score at discharge, but not FIM change. For both total FIM score and Motor FIM score at discharge, age alone accounted for only 3% of the variation in outcome. For all the models, age explained at the most 1.3% of the variation in functional outcome after adjustment for other factors, such as admission FIM score. CONCLUSIONS: The small amount of variation that can be explained by age alone and the questionable clinical relevance of such a small effect suggest that there is no justification to deny patients access to rehabilitation solely because of advanced age. PMID- 11779909 TI - Does acupuncture have additional value to standard poststroke motor rehabilitation? AB - BACKGROUND AND PURPOSE: A significant number of patients remain severely disabled after stroke despite rehabilitation with standard treatment modalities. Acupuncture has been reported as an alternative modality. This study aims to examine whether acupuncture has additional value to standard poststroke motor rehabilitation. METHODS: A prospective randomized controlled trial (RCT) was carried out in a stroke rehabilitation unit in Hong Kong. One hundred six Chinese patients with moderate or severe functional impairment were included at days 3 to 15 after acute stroke. They were stratified into the moderate and the severe groups before randomization into the control arm receiving standard modalities of treatment, which included physiotherapy, occupational and speech therapy, and skilled medical and nursing care, and the intervention arm receiving in addition traditional Chinese manual acupuncture. A mean of 35 acupuncture sessions on 10 main acupoints were performed over a 10-week period. Outcome measures included Fugl-Meyer assessment, Barthel Index, and Functional Independence Measure, respectively, at weeks 0, 5, and 10, performed by blinded assessors. RESULTS: At baseline, patients in each arm were comparable in all important prognostic characteristics. No statistically significant differences were observed between the 2 arms for any of the outcome measures at week 10 or outcome changes over time. CONCLUSIONS: Traditional Chinese manual acupuncture on the body has no additional value to standard poststroke motor rehabilitation. PMID- 11779910 TI - Incidence of aneurysmal subarachnoid hemorrhage in Shimokita, Japan, from 1989 to 1998. AB - BACKGROUND AND PURPOSE: The incidence of subarachnoid hemorrhage (SAH) has been investigated in many studies. A recent study in Izumo, Japan, indicates that the incidence of SAH is as high as that in Finland. The purpose of this study was to confirm the high incidence of SAH in Japan. METHODS: The incidence rate of SAH was investigated from 1989 through 1998 in the Shimokita peninsula, which is a clearly defined closed-boundary area in northern Japan with a population of 89 991. The registration was based on the complete referral system of SAH patients. All cases suspected of SAH underwent CT scan, and the images were referred to stroke specialists. The moribund cases and dead-on-arrival cases suspected of SAH also underwent CT scan. RESULTS: From 1989 through 1998, 198 cases were diagnosed as having aneurysmal SAH. Out of these, 26 cases were moribund or dead when the initial CT scan was performed. The age-adjusted annual incidence of SAH was 21 per 100 000 person-years. The age and sex distribution of the cases indicated that the incidence plateaued after age 45 in men and the incidence increased after age 45 and reached the peak after 75 years in women. CONCLUSIONS: The high incidence of SAH in Japan is confirmed. The incidence of SAH obtained in this study is near to that of the Izumo study, of which the size of the geographic region and denominator and diagnostic criteria were similar to this study. PMID- 11779911 TI - Predictors of cognitive dysfunction after subarachnoid hemorrhage. AB - BACKGROUND: Cognitive dysfunction is a common and disabling sequela of subarachnoid hemorrhage (SAH). Although several clinical and radiographic findings have been implicated in the pathogenesis of cognitive dysfunction after SAH, few prospective studies have comprehensively and simultaneously evaluated these risk factors. METHODS: Between July 1996 and March 2000, we prospectively evaluated 113 of 248 consecutively admitted nontraumatic SAH patients alive at 3 months with a comprehensive neuropsychological evaluation. Summary scores for 8 cognitive domains were calculated to express test performance relative to the entire study population. Clinical and radiographic variables associated with domain-specific cognitive dysfunction were identified with forward stepwise multiple regression, with control for the influence of demographic factors. RESULTS: The study participants were younger (P=0.005), less often white (P=0.006), and had better 3-month modified Rankin scores (P=0.001) than those who did not undergo neuropsychological testing. The proportion of subjects who scored in the impaired range (>2 SD below the normative mean) on each neuropsychological test ranged from 10% to 50%. Predictors of cognitive dysfunction in 2 or more domains in the multivariate analysis included global cerebral edema (4 domains), left-sided infarction (3 domains), and lack of a posterior circulation aneurysm (2 domains). Other variables consistently associated with cognitive dysfunction in the univariate analysis included admission Hunt-Hess grade >2 and thick SAH in the anterior interhemispheric and sylvian fissures. CONCLUSIONS: Global cerebral edema and left-sided infarction are important risk factors for cognitive dysfunction after SAH. Treatment strategies aimed at reducing neurological injury related to generalized brain swelling, infarction, and clot-related hemotoxicity hold the best promise for improving cognitive outcomes after SAH. PMID- 11779912 TI - Endovascular treatment of intracranial aneurysms with Guglielmi detachable coils: analysis of midterm angiographic and clinical outcomes. AB - BACKGROUND AND PURPOSE: The previous decade has witnessed increasing application of Guglielmi detachable coils (GDCs) for the treatment of intracranial aneurysms. However, the midterm angiographic and clinical outcomes are not well documented. We report here the angiographic and clinical outcomes of patients treated with GDCs over an 8-year period. METHODS: Between 1992 and 1998, 144 patients with 160 intracranial aneurysms were treated with GDCs. Clinical follow-up data were obtained from medical records, questionnaires, and telephone interviews. Angiographic studies were reviewed by 2 neuroradiologists to obtain consensus regarding the degree of aneurysm occlusion. RESULTS: Eighty-one patients had ruptured aneurysms; 63 had unruptured aneurysms. Technical success was achieved in 91% of patients, with complete aneurysm occlusion in 46%, neck remnants in 16%, and residual body filling in 38%. Angiographic follow-up revealed that residual body filling in some aneurysms was resolved, small neck remnants were stable, and the recanalization rate decreased with time. All 63 patients with unruptured aneurysms were discharged from hospital with independent clinical status (Glasgow Outcome Score, 1 or 2). For patients with ruptured aneurysms, discharge clinical status correlated with the Hunt & Hess clinical grade at the time of treatment. Clinical follow-up for a minimum of 2 years was available in 98.5% of patients. Ninety-four percent of patients treated for unruptured aneurysms were independent at 2 years, and 82% of Hunt & Hess grade I to II patients were independent. CONCLUSIONS: Coil embolization is a safe and effective treatment for both ruptured and unruptured aneurysms. Increasing angiographic stability is demonstrated in treated aneurysms up to 3 years from coil embolization. Therefore, follow-up angiography until this time is advisable. PMID- 11779913 TI - Different measures for assessing stroke outcome: an analysis from the International Stroke Trial in Italy. AB - BACKGROUND AND PURPOSE: We sought to assess the relationship between 2 simple questions on recovery (question 1: do you feel that you have made a complete recovery from your stroke?) and dependency (question 2: do you require help from another person for everyday activities?) and the Barthel Index (BI) and Oxford Handicap Scale (OHS), as well as the relationship between BI and OHS, in a large number of Italian stroke survivors who participated in the International Stroke Trial (IST). METHODS: We used data from 2423 patients interviewed by telephone at 6 months after the event. The kappa statistic, sensitivity, and specificity were calculated for several comparisons. Internal consistency for BI was calculated. RESULTS: The reliability of the dependency question compared with BI=20 (kappa=0.93) and the reliability of the recovery question compared with OHS=0 (kappa=0.89) were good. Sensitivity of the dependency question in predicting whether patients scored BI >18 was 0.98; sensitivity of the recovery question in predicting whether patients scored OHS=0 was 0.99. The reliability of BI=20 compared with OHS <3 was good (kappa=0.87). Internal consistency of BI was very high (Cronbach's alpha=0.96). CONCLUSIONS: The 2 simple questions are a good means of evaluating outcome from a patient's view and of dichotomizing the stroke survivor in a time-effective and reliable way. PMID- 11779914 TI - Cerebral atherosclerosis as predictor of stroke and mortality in representative elderly population. AB - BACKGROUND AND PURPOSE: The aim of this study was to assess the relationship between cardiovascular risk factors, atherosclerotic disease in the carotid bifurcation, and the risk of stroke and mortality in a representative population sample. METHODS: One hundred forty-two men and women participated in a population study at ages 70 and 76 years. At age 78, extracranial and intracranial circulation was examined by means of duplex sonography and transcranial Doppler techniques. Mortality and hospitalization for stroke were analyzed over a 5-year follow-up period up to age 83 years. RESULTS: Carotid plaques were identified in 82% of the men and 79% of the women. Bilateral plaques were found in 57% of the men and 46% of the women, and stenosis resulting in >50% diameter reduction occurred in 28% of the men and 17% of the women. Carotid stenosis >75% was observed in 7 subjects (0.5%). Bilateral plaques at age 78 were correlated with systolic blood pressure and ischemic heart disease at age 70 years. The pulsatility index was 1.0 to 1.4 in 63% and > or =1.5 in 13% of the study population. The pulsatility index was correlated with systolic and diastolic blood pressure, serum cholesterol, and triglycerides. Men with bilateral carotid plaques at age 78 years had an increased risk of stroke or mortality during the 5 year follow-up period (74% bilateral plaques versus 21% unilateral or no plaques). This was not found in the women (33% versus 26%). CONCLUSIONS: Carotid atherosclerosis was prevalent in a majority of elderly subjects. Bilateral plaques were correlated with systolic blood pressure and ischemic heart disease at age 70 years and predicted the risk of stroke and mortality in men but not in women. PMID- 11779915 TI - Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study: A comparison of incidence and risk factor effects. AB - BACKGROUND AND PURPOSE: Risk of death due to stroke in Japan is more than double the risk in the United States. It remains unknown why some ethnic groups are more prone to stroke than others. Our purpose was to compare the 20-year incidence of hospitalized stroke between Japanese-American men in the Honolulu Heart Program and white men in the Framingham Study. METHODS: This was a 20-year follow-up study beginning around 1965, a population-based study on the island of Oahu, Hawaii, and in Framingham, Mass. Participants were 7589 men in Honolulu and 1216 men in Framingham without prevalent coronary heart disease and stroke. Subjects were 45 to 68 years old when follow-up began. Main outcome measures were incident thromboembolic and hemorrhagic stroke. RESULTS: Framingham men had a 40% excess of thromboembolic stroke compared with Honolulu men after adjustment for age and other risk factors (62/1000 versus 45/1000, respectively, P<0.001), whereas incidence of hemorrhagic stroke was nearly identical (14.8/1000). In both cohorts, each stroke type was consistently elevated in the presence of hypertension and cigarette smoking. Diabetes and body mass index increased the risk of thromboembolic stroke in both samples, and diabetes increased the risk of hemorrhagic events in Framingham. Alcohol intake and low total cholesterol were associated with hemorrhagic events in Honolulu but not in Framingham. Despite occasional differences in risk factor effects, none were significantly different between cohorts. CONCLUSIONS: The incidence of thromboembolic stroke requiring hospitalization is markedly less in Honolulu than in Framingham. The difference in stroke incidence rates observed cannot be explained by the traditional risk factors. Further studies are needed to identify factors that protect Japanese American men in Honolulu from stroke. PMID- 11779916 TI - Ethnic differences in patient perceptions of atrial fibrillation and anticoagulation therapy: the West Birmingham Atrial Fibrillation Project. AB - BACKGROUND AND PURPOSE: We hypothesized that different ethnic groups would have different levels of knowledge and perceptions of atrial fibrillation (AF) and of their antithrombotic therapy. To investigate this further, we conducted a cross sectional survey of patients with documented chronic AF who were attending the anticoagulation clinic in our city center teaching hospital, serving a multiethnic population. METHODS: We surveyed 119 patients (77 male; mean age 69+/ 9 years [mean+/-SD]); of these, 39 were Indo-Asian (33%), 27 Afro-Caribbean (23%), and 53 white (44%). RESULTS: Only 63% of patients in the overall study cohort were aware of their cardiac condition, with Indo-Asians and Afro Caribbeans significantly less aware of AF compared with the white patients (P<0.001). When questioned about the perception of the severity of the underlying condition, the majority (61%) felt that AF was "not serious." A large proportion were unaware that AF predisposed to thrombosis and stroke; among the ethnic groups, Indo-Asians appeared to be the least aware of the stroke and thromboembolic associations of AF. Only 52% in the whole cohort were aware of the reason(s) for commencing their warfarin, whereas the remainder began warfarin therapy simply because their "doctor told them to." Most patients in the whole cohort were aware of warfarin being used to prevent blood clots (65%) or stroke (66%), but Indo-Asians and Afro-Caribbeans were less so. Only 45% of the study cohort believed that there was some risk associated with warfarin therapy in the form of either "bleeding" or "poisoning." Only a minority of Indo-Asians and Afro Caribbeans with AF felt that their doctor had given them enough information about their warfarin therapy, and many from these ethnic groups felt that they were careless about taking their warfarin. CONCLUSIONS: In conclusion, many patients with AF possess very limited knowledge of AF as well as its consequences and therapy. In particular, our study has highlighted significant differences between different ethnic groups in terms of their knowledge of the risks, actions, and benefits of warfarin as well as of AF itself. PMID- 11779917 TI - Severity of angina pectoris and risk of ischemic stroke. AB - BACKGROUND AND PURPOSE: Ischemic stroke and coronary heart disease (CHD) share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We examined the relationship between severity of angina pectoris and its accompanying characteristics and the risk of incident ischemic stroke. METHODS: We traced 3122 patients with stable CHD, included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. CHD was documented by a history of myocardial infarction > or =6 months and < 5 years before enrollment and/or stable angina pectoris with evidence of ischemia confirmed by ancillary diagnostic testing. Severity of angina pectoris was assessed according to the Canadian Cardiovascular Society angina classification, and heart failure functional class according to the New York Heart Association (NYHA) classification. Patients with severe heart failure or unstable angina on enrollment were excluded. RESULTS: During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The cumulative rate of ischemic stroke increased in a dose-response manner from 4.7% in patients with no angina to 5.7%, 8.4%, and 12.9% in patients with angina classes 1, 2, and 3, respectively (P<0.001). Patients with NYHA functional class 1 had a 5.5% rate of ischemic stroke versus 7.3% and 9.6% in patients with classes 2 and 3, respectively (P=0.05). In a Cox proportional-hazard model adjusting for conventional risk factors and potential confounders, the hazard ratio associated with angina class 1 was 1.20 (95% CI, 0.83 to 1.74); class 2, 1.66 (95% CI, 1.12 to 2.45); and class 3, 2.35 (95% CI, 1.08 to 5.13), as compared with patients with no angina. Hazard ratios of ischemic stroke associated with conventional risk factors were 1.55 for a 10-year age increment, 2.16 for diabetes mellitus, 1.81 for current smoking, and 1.29 for a 20 mm Hg increase in systolic blood pressure. CONCLUSIONS: Severity of angina pectoris in patients with stable CHD predicts an increased risk of subsequent ischemic stroke. The association between angina class and incident ischemic stroke is independent of traditional vascular risk factors. PMID- 11779919 TI - Cooling-induced carotid artery dilatation: an experimental study in isolated vessels. AB - BACKGROUND AND PURPOSE: Clinical and experimental studies seem to indicate that hypothermia may improve outcome in stroke victims and reduce experimental brain injury. The current interpretation is that cooling has a neuroprotective effect by reducing brain metabolism. The objective of our study was to test the hypothesis that hypothermia induces arterial vasodilatation and thereby increases cerebral blood flow. METHODS: We recorded isometric tension in rabbit carotid artery strips in organ baths during stepwise cooling. The cooling responses were tested at basal tone, in noradrenaline-precontracted vessels, and after electric field stimulation. RESULTS: Stepwise cooling from 37 degrees C to 4 degrees C induced reproducible graded relaxation, inversely proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Cooling decreased the contractile responses to norepinephrine and potassium chloride. Cooling at 20 degrees C decreased the contractile responses to electric field stimulation, while at 10 degrees C these were totally abolished. Cooling induced vasodilatation is not dependent on an endothelial mechanism. CONCLUSIONS: Cooling of carotid artery preparations induced a reversible graded vasodilatation and decreased or abolished the effect of vasocontractile neurotransmitters. The effect of local hypothermia could increase cerebral blood flow and may constitute a positive therapeutic modality in stroke patients. PMID- 11779918 TI - Activation-induced resetting of cerebral metabolism and flow is abolished by beta adrenergic blockade with propranolol. AB - BACKGROUND AND PURPOSE: It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR(glc)) in excess of cerebral oxygen uptake (CMRO(2)). Our purpose was to investigate the influence of beta-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism. METHODS: Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(a-v)(O2)], glucose [(a-v)(glc)], and lactate [(a-v)(lac)] both under baseline conditions and during activation. The molar ratio between CMRO(2) and CMR(glc), the oxygen glucose index (OGI), was calculated. RESULTS: Without beta-adrenergic blockade, activation decreased the (a-v)(O2) but not the (a-v)(glc), reducing the OGI from 6.1 during baseline conditions to 4.0 under activation (P<0.01). The (a-v)(O2) decreased, indicating that the ratio CBF/CMRO(2) had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but beta-adrenergic blockade totally abolished the activation-induced uncoupling of (a-v)(O2) from (a-v)(glc), because both remained constant with an unchanged OGI. The unchanged (a-v)(O2) indicates that CBF remained unchanged compared with CMRO(2). CONCLUSIONS: beta-Adrenergic blockade by propranolol abolishes the activation-induced uncoupling of cerebral oxygen to glucose metabolism and the changes in (a-v)(O2). This may be of most significance to studies of cerebral activation by the blood oxygen level-dependent fMRI method. PMID- 11779920 TI - Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen glucose deprivation. AB - BACKGROUND AND PURPOSE: Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects. The aim of this study was to elucidate its direct neuroprotective effects. METHODS: Viability parameters, glutamate release and uptake, and ATP levels were measured in cultured cortical neurons exposed to oxygen-glucose deprivation (OGD). In addition, ATP levels and oxygen consumption were studied in isolated brain mitochondria or submitochondrial particles. RESULTS: Aspirin inhibited OGD induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition of the transcription factor nuclear factor-kappaB (which are >1 mmol/L), an effect that correlated with the inhibition caused by aspirin on glutamate release. This effect was shared by sodium salicylate but not by indomethacin, thus excluding the involvement of cyclooxygenase. A pharmacological dissection of the components involved indicated that aspirin selectively inhibits the increase in extracellular glutamate concentration that results from reversal of the glutamate transporter, a component of release that is due to ATP depletion. Moreover, aspirin-afforded neuroprotection occurred in parallel with a lesser decrease in ATP levels after OGD. Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase in NADH-dependent respiration by brain submitochondrial particles. CONCLUSIONS: Taken together, our present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at concentrations in the antithrombotic-analgesic range, useful in the management of patients with high risk of ischemic events. PMID- 11779921 TI - Effect of socioeconomic status on treatment and mortality after stroke. AB - BACKGROUND AND PURPOSE: Socioeconomic status is associated with increased mortality from ischemic heart disease. We undertook a study to determine whether a similar association exists between socioeconomic status and stroke mortality. METHODS: We linked hospital discharge abstracts and vital-status data for all patients with acute stroke admitted to hospitals in Ontario between April 1994 and March 1997. Socioeconomic status for each patient was inferred on the basis of median neighborhood income. We determined the risk of death at 30 days and 1 year; secondary analyses compared the use of medications, inpatient rehabilitation services, and carotid endarterectomy by socioeconomic status. We used multivariate analyses to adjust for age, sex, stroke type, comorbid conditions, and hospital and physician characteristics. RESULTS: The study sample consisted of 38 945 patients. Each $10 000 increase in median neighborhood income was associated with a 9% reduction in the hazard of death at 30 days (adjusted hazard ratio 0.91, 95% CI 0.87 to 0.96) and a 5% reduction in the hazard of death at 1 year (adjusted hazard ratio 0.95, 95% CI 0.92 to 0.99). Patients in the lowest income quintile were less likely than those in the highest to receive in hospital physiotherapy (58% versus 61%, P<0.001), occupational therapy (36% versus 47%, P<0.001), and speech pathology (21% versus 28%, P<0.001). There were no differences in the use of medications or carotid endarterectomy based on socioeconomic status. Waiting times for carotid surgery, however, were significantly longer in the lowest income quintile than the highest (90 days versus 60 days, P=0.002). CONCLUSIONS: Socioeconomic status affects mortality and access to some health services after stroke, even in a country with a universal health insurance program. Understanding and reducing these socioeconomic disparities should be a priority for future research. PMID- 11779922 TI - CT angiography in acute ischemic stroke: preliminary results. AB - BACKGROUND AND PURPOSE: We sought to evaluate the ability of CT angiography (CTA) to determine vessel occlusion before acute stroke treatment and to predict its impact on patient outcome. METHODS: Consecutive patients with acute focal neurological deficits received immediate brain CTA. Occlusion on CTA was correlated with other neuroimaging studies and clinical outcome. RESULTS: Diagnostic CTA was obtained in 54 patients: catheter angiography (digital subtraction angiography) confirmed the CTA findings in 12 of 14 patients (86%). CTA results were consistent with at least 1 other neuroimaging study in 40 of 50 patients (80%). Patients with occlusion on CTA had significantly worse discharge National Institutes of Health Stroke Scale (NIHSS) score (mean 14.3 versus 4.5, P=0.0023). In multivariate analysis, both CTA-determined presence of occlusion and admission NIHSS score were independent predictors of clinical outcome. CONCLUSIONS: In our study there was good agreement between acute CTA interpretation and subsequent imaging studies. CTA evidence of occlusion correlated strongly and independently with poor clinical outcome. CTA provides relevant data regarding vessel patency in acute stroke, which may be of value in selecting patients for aggressive treatment. PMID- 11779923 TI - Acute intravenous--intra-arterial revascularization therapy for severe ischemic stroke. AB - BACKGROUND: Intravenous alteplase for acute ischemic stroke is least efficacious for patients with proximal large-artery occlusions and clinically severe strokes. Intra-arterial therapy has the theoretical advantage of establishing a neurovascular diagnosis and high symptomatic artery patency rate but the disadvantage of requiring extra time and technical expertise. A combination of these two approaches may provide the best chance of improving outcome in severe acute ischemic stroke. We sought to assess the safety and feasibility of this approach. METHODS: This was a prospective, open-label study. Sequential patients arriving to our center within 3 hours of stroke onset who were treated with intravenous alteplase were screened for possible additional intra-arterial therapy using noninvasive neuroimaging. Clinical measures and outcomes were recorded prospectively. RESULTS: A total of 861 patients with ischemic stroke were admitted to Calgary hospitals during the study period. Eight patients over 21 months underwent a combined intravenous-intra-arterial approach. Six received intra-arterial alteplase and 1 underwent intracranial angioplasty; in a final patient, technical aspects prevented intra-arterial therapy. Early neurovascular and/or neurometabolic imaging identified the location of occlusion and tissue-at risk (DWI-PWI mismatch) in all 8 patients. Two patients had a poor outcome, 1 patient suffered a significant groin hematoma, and there were no instances of symptomatic intracerebral hemorrhage. CONCLUSIONS: Intravenous followed by intra arterial therapy is a promising approach to the treatment of severe acute ischemic stroke. Early noninvasive neurovascular and neurometabolic imaging is very helpful in choosing candidates for this type of therapy. On-going monitoring of alteplase-treated patients may allow the opportunity to perform rescue intra arterial therapy. PMID- 11779924 TI - Reemergence of stroke deficits with midazolam challenge. AB - BACKGROUND AND PURPOSE: Patients who have sustained a neurological injury and then improved may experience transient reemergence of their syndromes when given benzodiazepines. As a step toward assessing whether neurotransmitter systems underlie poststroke clinical improvement, we selected midazolam, a gamma aminobutyric acid(A) (GABA(A)) agonist, for systemic administration to measure general or stroke-specific effects in patients. METHODS: Eight patients with image-verified stroke (5 with left-sided and 3 with right-sided cerebral lesions) participated. The strokes had occurred from 7 days to 6 years earlier, with patients showing clinical improvement from their initial syndromes. Each patient underwent baseline testing for motor function, aphasia, and left hemispatial neglect, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during this period and again after 2 hours when sedation had dissipated. RESULTS: After the administration of midazolam, the 5 patients with left hemisphere stroke demonstrated reemergence or worsening of their initial right hemiparesis and aphasia but showed no left neglect. The 3 patients with right cerebral stroke showed reemergence of left hemiparesis and left visual field neglect but no aphasia. All patients returned to baseline after 2 hours. CONCLUSIONS: Under conditions of light sedation, patients whose initial stroke syndrome had substantially improved clinically showed transient reemergence of their initial focal syndrome. These data suggest a possible role for GABA(A)-mediated neurochemical mechanisms in poststroke improvement and sensitivity to medication effects. PMID- 11779925 TI - Creatine kinase-MB elevation after stroke is not cardiac in origin: comparison with troponin T levels. AB - BACKGROUND AND PURPOSE: Creatine kinase-MB (CK-MB) increases in some patients with stroke, with no clear evidence of an acute coronary syndrome. Its elevations have been suggested to represent a biological marker for stroke-related myocardial injury. Troponin T has superior sensitivity and specificity to CK-MB in revealing minor myocardial injury. Therefore, we studied troponin T levels after stroke to determine whether troponin T increases in parallel to CK-MB. METHODS: We made daily measurements of CK-MB, myoglobin, total creatine kinase (total CK), and troponin T levels up to day 5 in 32 patients with large hemispheric infarction and with no history of coronary heart disease. The daily enzyme levels were compared with those of a control group of 22 patients with neurological diseases other than stroke. RESULTS: Serum CK-MB, myoglobin, and total CK levels were elevated above the cutoff value in 11, 26, and 20 patients with stroke, respectively. These enzyme levels gradually increased within the first 3 days and declined afterward. Troponin T did not exceed the reference range in any patients. One patient had elevated myoglobin and 3 had elevated total CK in the control group. The difference between groups was significant for CK-MB, myoglobin, and total CK at various time points. CONCLUSIONS: Troponin T, a more specific biochemical marker of myocardial injury, does not increase after stroke. Normal troponin T along with elevated CK-MB signifies that CK-MB is not the biological marker for myocytolysis. CK-MB elevations in stroke patients are likely to be noncardiac in origin. PMID- 11779926 TI - Mastoid air sinus abnormalities associated with lateral venous sinus thrombosis: cause or consequence? AB - BACKGROUND: Mastoiditis is a known cause of lateral venous sinus thrombosis (LST). We have encountered patients with LST associated with mastoid abnormality on MRI without any clinical signs of infection; the significance of these abnormalities is uncertain. This study examines the relationship of LST and mastoid air sinus abnormalities systematically. SUMMARY OF REPORT: We performed a retrospective clinical and radiological review of a series of 26 patients with cerebral venous thrombosis. Mastoid abnormalities were detected ipsilateral to 9 of 23 thrombosed lateral sinuses (39%) and 0 of 29 unaffected lateral sinuses (P<0.001). No patient had clinical evidence of mastoiditis. Eight of 9 patients with mastoid abnormalities were treated without antibiotics; all made uneventful clinical recoveries. Repeated MRI in 1 patient revealed reversal of the mastoid changes. CONCLUSIONS: The mastoid changes observed are likely to be due to venous congestion as a consequence of LST, not mastoiditis. PMID- 11779927 TI - Transesophageal echocardiography for quantifying size of patent foramen ovale in patients with cryptogenic cerebrovascular events. AB - BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) is a risk factor for paradoxical embolism, and severe shunting and wide opening of PFO are risk factors for severe and recurrent cerebrovascular events. Neither contrast echocardiography nor 2-dimensional (2D) measurement of PFO size have been validated or compared with invasive balloon sizing. METHODS: We performed transesophageal echocardiography (TEE) in 100 patients with cryptogenic stroke and catheter closure of PFO. The amount of contrast shunting through the PFO during cubital and femoral contrast delivery and the PFO size measured by 2D TEE were compared with balloon sizing. RESULTS: There was a significant correlation (r(2)=0.8; P<0.0001) between 2D TEE measurement and invasive balloon sizing. Mean balloon-sized PFO diameter was significantly larger than mean PFO diameter measured by 2D TEE (8.3+/-2.6 versus 5.2+/-1.7 mm). Semiquantitative contrast TEE correlated with PFO size (r(2)=0.7; P<0.0001) only if the contrast agent was administered through a femoral vein. Correlation was poor when the contrast agent was administered via a cubital vein. CONCLUSIONS: We conclude that 2D TEE measurement of a PFO size is more accurate than the traditionally used contrast technique. PMID- 11779928 TI - Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct. AB - BACKGROUND AND PURPOSE: A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events. METHODS: One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis. RESULTS: Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events. CONCLUSIONS: Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events. PMID- 11779929 TI - Neuroprotection is unlikely to be effective in humans using current trial designs. PMID- 11779930 TI - Neuroprotection is unlikely to be effective in humans using current trial designs: an opposing view. PMID- 11779931 TI - Neuroprotection: establishing proof of concept in human stroke. PMID- 11779932 TI - NINDS-sponsored clinical trials in stroke: past, present, and future. PMID- 11779933 TI - Endovascular treatment of aneurysms in the cavernous sinus: a systematic review on balloon occlusion of the parent vessel and embolization with coils. AB - BACKGROUND AND PURPOSE: Balloon occlusion of the parent vessel and endosaccular coiling are both frequently used for treatment of intracavernous aneurysms of the carotid artery. We performed a systematic review of studies reporting on these two treatment modalities to assess the rate of complications, rate of successful aneurysm occlusion, and clinical condition after treatment. METHODS: We performed a MEDLINE search for studies published between January 1974 and May 1999 and hand searched recent volumes of 21 journals. Two authors independently extracted data by means of a standardized data extraction form. RESULTS: We found 35 studies reporting on 316 patients. Only 9 of the 35 studies reported on more than 5 patients; in only 9 studies (totaling 85 patients), well-defined outcome measures were used. Twenty-five studies (with 78% of all patients included in the review) reported on balloon occlusion. Complications during or in the first 24 hours after the balloon occlusion occurred in 4 of 247 patients (1.6%; 95% CI, 0.01% to 3.2%) and late ischemic complications in 5 of 148 patients (3.4%; 95% CI, 0.43% to 6.4%). Clinical follow-up was performed in 21 of 25 studies on treatment by means of balloon occlusion (148 [60%] of the 247 patients). None of the 68 patients treated by embolization with coils had a complication (0%; 95% CI, 0% to 4.3%). Of 157 aneurysms treated by balloon occlusion, 153 were completely thrombosed (97.5%; 95% CI, 95% to 100%). After coiling, 52 of 65 aneurysms (80%; 95% CI, 70% to 90%) were occluded by >90%. CONCLUSIONS: Many studies included in this review had methodological weaknesses. The available data suggest that both balloon occlusion and endosaccular coiling are reasonably safe and result in occlusion of the aneurysm in the majority of patients. However, long-term outcomes have not yet been reported. PMID- 11779934 TI - The PROGRESS Trial: preventing strokes by lowering blood pressure in patients with cerebral ischemia. Emerging therapies: critique of an important advance. PMID- 11779935 TI - Cholesterol and carotid stenosis. PMID- 11779936 TI - Diurnal variation in the intensity of anticoagulation in atrial fibrillation. PMID- 11779937 TI - Reasons why stroke trials underestimate the neuroprotective effects of drugs. PMID- 11779938 TI - Recommendations for improving the quality of care through stroke centers and systems: an examination of stroke center identification options: multidisciplinary consensus recommendations from the Advisory Working Group on Stroke Center Identification Options of the American Stroke Association. AB - BACKGROUND AND PURPOSE: The American Stroke Association (ASA) assembled a multidisciplinary group of experts to develop recommendations regarding the potential effectiveness of establishing an identification program for stroke centers and systems. "Identification" refers to the full spectrum of models for assessing and recognizing standards of quality care (self-assessment, verification, certification, and accreditation). A primary consideration is whether stroke center identification might improve patient outcomes. METHODS: In February 2001, ASA, with the support of the Stroke Council's Executive Committee, decided to embark on an evaluation of the potential impact of stroke center identification. HealthPolicy R&D was selected to prepare a comprehensive report. The investigators reported on models outside the area of stroke, ongoing initiatives within the stroke community (such as Operation Stroke), and state and federal activities designed to improve care for stroke patients. The investigators also conducted interviews with thought leaders in the stroke community, representing a diverse sampling of specialties and affiliations. In October 2001, the Advisory Working Group on Stroke Center Identification developed its consensus recommendations. This group included recognized experts in neurology, emergency medicine, emergency medical services, neurological surgery, neurointensive care, vascular disease, and stroke program planning. RESULTS: There are a variety of existing identification programs, generally falling within 1 of 4 categories (self-assessment, verification, certification, and accreditation) along a continuum with respect to intensity and scope of review and consumption of resources. Ten programs were evaluated, including Peer Review Organizations, trauma centers, and new efforts by the National Committee on Quality Assurance and the Joint Commission on the Accreditation of Healthcare Organizations to identify providers and disease management programs. The largest body of literature on clinical outcomes associated with identification programs involves trauma centers. Most studies support that trauma centers and systems lead to improved mortality rates and patient outcomes. The Advisory Working Group felt that comparison to the trauma model was most relevant given the need for urgent evaluation and treatment of stroke. The literature in other areas generally supports the positive impact of identification programs, although patient outcomes data have less often been published. In the leadership interviews, participants generally expressed strong support for pursuing some form of voluntary identification program, although concerns were raised that this effort could meet with some resistance. CONCLUSIONS: Identification of stroke centers and stroke systems competencies is in the best interest of stroke patients in the United States, and ASA should support the development and implementation of such processes. The purpose of a stroke center/systems identification program is to increase the capacity for all hospitals to treat stroke patients according to standards of care, recognizing that levels of involvement will vary according to the resources of hospitals and systems. PMID- 11779939 TI - New opportunities in biological and chemical crystallography. AB - Banerjee [Proc. R. Soc. (1933), 141, 188-193] offered a new way of approaching the crystallographic phase problem which not only broke new ground beyond the 'trial and error' structure solution method of that time but also heralded the extremely powerful direct methods of crystallography of the modern era from the 1970s onwards in chemical crystallography. Some 200000 crystal structures are known today. More complex crystal structures such as proteins required new experimental and theoretical methods to solve the phase problem. These are still evolving, and new methods and results involving synchrotron radiation at softer X ray wavelengths (2 A) are reported. In addition, an overview is given of the new opportunities that are possible for biological and chemical crystallography, especially via harnessing synchrotron radiation and neutron beams. PMID- 11779940 TI - A multiple-scattering theory of circular and linear dichroism for photoemission and photoabsorption. AB - A unified treatment of circular dichroism, both natural and magnetic, in (spin resolved) photoemission and photoabsorption from core levels is given, valid in the many-body case and for extended systems, together with an extension of the formalism to treat linear dichroism. The reduction of this scheme to a one electron picture in the framework of multiple scattering theory is briefly discussed and shows the intimate connection of the two spectroscopies via a generalized optical theorem. Plausibility arguments are given that in correlated d-band systems screening and relaxation effects are not so drastic as in other cases, due to the autoscreening action of the excited photoelectron, so that the final density of states is much like the initial unperturbed one. It is shown how to exploit this point of view to obtain in favorables cases separated orbital and spin moment radial (surface) distribution maps from dichroic magnetic EXAFS spectra (photoelectron diffraction patterns) related to the ground state. Dichroic natural spectra, both in photoemission and absorption, are shown to be sensitive only to atoms in chiral geometry. PMID- 11779944 TI - High-sensitivity CCD-based X-ray detector. AB - The detector is designed for imaging measurements requiring relatively high sensitivity and high spatial resolution. The detector can discriminate single X ray photons, yet has the wide dynamic range ( approximately 10000:1) associated with integrating detectors. A GdO2S2 phosphor screen converts the incoming X-ray image into an optical image. The optical image is coupled (without demagnification) to the CCD image sensor using a fiber optic faceplate. The CCD (Philips Semiconductors) has an area of 4.9 x 8.6 cm with 4000 x 7000 12 microm pixels. A single 12 keV X-ray photon produces a signal of 100 e-. With 2 x 2 pixel binning, the total noise per 24 microm pixel in a 100 s image is approximately 30 e- the detective quantum efficiency is >0.6 at 1 X-ray photon per pixel, and the full image can be read out in <4 s. The spatial resolution is 50 microm. The CCD readout system is fully computer-controlled, allowing flexible operation in time-resolved experiments. The detector has been characterized using visible-light images, X-ray images and time-resolved muscle diffraction measurements. PMID- 11779945 TI - Design and performance of ESRF high-power undulator front-end components. AB - A new high-power front-end has been developed and installed at the European Synchrotron Radiation Facility. The new design consists of the replacement of the X-ray absorber and the filtering system. An upstream pre-slit and a compact high heat-load absorber have replaced the X-ray absorber. A chemical-vapour-deposition diamond window has replaced the beryllium window and graphite filters usually employed. Commissioning has been successfully performed on the ID23 test front end equipped with three U34 undulators producing synchrotron radiation with a total power of 11 kW and a peak power density of 1200 W mm(-2) at normal incidence. PMID- 11779956 TI - A holistic approach to population control in India. PMID- 11779954 TI - Current status of fertility control methods in India. AB - Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3.4% in 1992-93 to 1.9% in 1998-99. Use of the condom increased to 3.1% from 2.4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive 'Centchorman', which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e. Embelia ribes, Borax and Piper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive - a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc. PMID- 11779955 TI - Molecular approaches to contraceptive development. AB - The next generation of contraceptives will be based on the identification of novel molecules essential for reproductive processes and will rely on the refinement of older as well as newer technologies. Functional analysis of naturally occurring reproductive genetic disorders and creation of mice null for specific genes would greatly assist in the choice of genetic targets for contraceptive development. Structure-based design of drugs as exemplified by the preparation of an orally active non-peptide gonadotropin releasing hormone (GnRH) would revolutionize drug formulation and delivery for a peptide analogue. This review examines some of the molecular targets that may change contraceptive choices in the future. PMID- 11779957 TI - Is there a role for contraceptive vaccines in fertility control? PMID- 11779959 TI - Epidemiological profile of India: historical and contemporary perspectives. AB - Knowledge and understanding of the epidemiological profile is an essential pre requisite to assess and address public health needs in the country and to enable efficient programme planning and management. The need for adequate and accurate health information and data to undertake such an exercise cannot be over emphasized. The present effort is a modest attempt to critically analyse the epidemiological profile of India from the historical and contemporary perspective. In order to assess the successes achieved as well caution against the daunting challenges awaiting the country, parameters such as disease burden and health status indicators, are increasingly being used. Changes in the population age structure, improvements in the nation's economic status, altered life-styles of people and duality of disease burden testify to the demographic, development and health transition occurring in the country. Population stabilization, poverty alleviation, life-style modification, surveillance and control of communicable and non-communicable diseases constitute the major challenges demanding urgent attention in the future. PMID- 11779958 TI - Molecular insights into the causes of male infertility. AB - Infertility is a reproductive health problem that affects many couples in the human population. About 13-18% of couple suffers from it and approximately one half of all cases can be traced to either partner. Regardless of whether it is primary or secondary infertility, affected couples suffer from enormous emotional and psychological trauma and it can constitute a major life crisis in the social context. Many cases of idiopathic infertility have a genetic or molecular basis. The knowledge of the molecular genetics of male infertility is developing rapidly, new "spermatogenic genes" are being discovered and molecular diagnostic approaches (DNA chips) established. This will immensely help diagnostic and therapeutic approaches to alleviate human infertility. The present review provides an overview of the causes of human infertility, particularly the molecular basis of male infertility and its implications for clinical practice. PMID- 11779960 TI - Increasing population and declining biological resources in the context of global change and globalization. AB - In the context of over-consumption of natural resources in the name of development and rapid industrialization by a small section of the human population that is rapidly growing, the world is currently faced with a variety of environmental uncertainties. 'Global change' covering a whole variety of ecological issues, and 'globalization' in an economic sense, are two major phenomena that are responsible for these uncertainties. There is increasing evidence to suggest that the developing countries more than the developed, particularly the marginalized traditional (those living close to nature and natural resources) societies would be the worst sufferers. In order to cope with this problem in a situation where the traditional societies have to cope with rapidly depleting biodiversity on which they are dependant for their livelihood, there is an urgent need to explore additional pathways for sustainable management of natural resources and societal development. Such pathways should be based on a landscape management strategy, that takes into consideration the rich traditional ecological knowledge (TEK) that these societies have. This is critical because TEK is the connecting link between conservation and sustainable development. This paper explores the possibilities in this direction through a balanced approach to development, that links the 'traditional' with the 'modern', in a location specific way. PMID- 11779961 TI - Nutritional status of the Indian population. AB - High prevalence of low birth weight, high morbidity and mortality in children and poor maternal nutrition of the mother continue to be major nutritional concerns in India. Although nationwide intervention programmes are in operation over two decades, the situation has not changed greatly. In addition, the Indian population is passing through a nutritional transition and is expected to witness higher prevalences of adult non-communicable diseases such as diabetes, hypertension and coronary heart disease according to the theory of 'fetal origin of adult disease'. Clearly, there is a need for examining several issues of nutritional significance for effective planning of interventions. In particular, maternal nutrition and fetal growth relationship, long term effects of early life undernutrition, interactions of prenatal nutritional experiences and postnatal undernutrition are some of the major issues that have been discussed in the present paper with the help of prospective data from various community nutrition studies carried out in the department. PMID- 11779962 TI - Prehistoric human colonization of India. AB - Human colonization in India encompasses a span of at least half-a-million years and is divided into two broad periods, namely the prehistoric (before the emergence of writing) and the historic (after writing). The prehistoric period is divided into stone, bronze and iron ages. The stone age is further divided into palaeolithic, mesolithic and neolithic periods. As the name suggests, the technology in these periods was primarily based on stone. Economically, the palaeolithic and mesolithic periods represented a nomadic, hunting-gathering way of life, while the neolithic period represented a settled, food-producing way of life. Subsequently copper was introduced as a new material and this period was designated as the chalcolithic period. The invention of agriculture, which took place about 8000 years ago, brought about dramatic changes in the economy, technology and demography of human societies. Human habitat in the hunting gathering stage was essentially on hilly, rocky and forested regions, which had ample wild plant and animal food resources. The introduction of agriculture saw it shifting to the alluvial plains which had fertile soil and perennial availability of water. Hills and forests, which had so far been areas of attraction, now turned into areas of isolation. Agriculture led to the emergence of villages and towns and brought with it the division of society into occupational groups. The first urbanization took place during the bronze age in the arid and semi-arid region of northwest India in the valleys of the Indus and the Saraswati rivers, the latter represented by the now dry Ghaggar-Hakra bed. This urbanization is known as the Indus or Harappan civilization which flourished during 3500-1500 B.C. The rest of India during this period was inhabited by neolithic and chalcolithic farmers and mesolithic hunter-gatherers. With the introduction of iron technology about 3000 years ago, the focus of development shifted eastward into the Indo-Gangetic divide and the Ganga valley. The location of the Mahabharata epic, which is set in the beginning of the first millennium B.C., is the Indo-Gangetic divide and the upper Ganga-Yamuna doab (land between two rivers). Iron technology enabled pioneering farmers to clear the dense and tangled forests of the middle and lower Ganga plains. The focus of development now shifted further eastward to eastern Uttar Pradesh and western Bihar which witnessed the events of the Ramayana epic and rise of the first political entities known as Mahajanapadas as also of Buddhism and Jainism. The second phase of urbanization of India, marked by trade, coinage, script and birth of the first Indian empire, namely Magadha, with its capital at Pataliputra (modern Patna) also took place in this region in the sixth century B.C. The imposition by Brahmin priests of the concepts of racial and ritual purity, pollution, restrictions on sharing of food, endogamy, anuloma (male of upper caste eligible to marry a female of lower caste) and pratiloma (female of upper caste ineligible to marry a male of lower caste) forms of marriage, karma (reaping the fruits of the actions of previous life in the present life), rebirth, varnashrama dharma (four stages of the expected hundred-year life span) and the sixteen sanskaras (ceremonies) on traditional occupational groups led to the birth of the caste system - a unique Indian phenomenon. As a consequence of the expansion of agriculture and loss of forests and wildlife, stone age hunter-gatherers were forced to assimilate themselves into larger agriculture-based rural and urban societies. However, some of them resisted this new economic mode. To this day they have persisted with their atavistic lifestyle, but have had to supplement their resources by producing craft items or providing entertainment to the rural population. PMID- 11779964 TI - Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures. AB - The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian-thalamic nucleus (ESCM) for control of generalized tonic-clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike-wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic-clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient's subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory. PMID- 11779963 TI - Ethnic populations of India as seen from an evolutionary perspective. AB - It is now widely accepted that (i) modern humans, Homo sapiens sapiens, evolved in Africa, (ii) migrated out of Africa and replaced archaic humans in other parts of the world, and (iii) one of the first waves of out-of-Africa migration came into India. India, therefore, served as a major corridor for dispersal of modern humans. By studying variation at DNA level in contemporary human populations of India, we have provided evidence that mitochondrial DNA haplotypes based on RFLPs are strikingly similar across ethnic groups of India, consistent with the hypothesis that a small number of females entered India during the initial process of the peopling of India. We have also provided evidence that there may have been dispersal of humans from India to southeast Asia. In conjunction with haplotype data, nucleotide sequence data of a hypervariable segment (HVS-1) of the mitochondrial genome indicate that the ancestors of the present austro asiatic tribal populations may have been the most ancient inhabitants of India. Based on Y-chromosomal RFLP and STRP data, we have also been able to trace footprints of human movements from west and central Asia into India. PMID- 11779965 TI - Deep brain stimulation in epilepsy. AB - Since the pioneering studies of Cooper et al. to influence epilepsy by cerebellar stimulation, numerous attempts have been made to reduce seizure frequency by stimulation of deep brain structures. Evidence from experimental animal studies suggests the existence of a nigral control of the epilepsy system. It is hypothesized that the dorsal midbrain anticonvulsant zone in the superior colliculi is under inhibitory control of efferents from the substantia nigra pars reticulata. Inhibition of the subthalamic nucleus (STN) could release the inhibitory effect of the substantia nigra pars reticulata on the dorsal midbrain anticonvulsant zone and thus activate the latter, raising the seizure threshold. Modulation of the seizure threshold by stimulation of deep brain structures-in particular, of the STN-is a promising future treatment option for patients with pharmacologically intractable epilepsy. Experimental studies supporting the existence of the nigral control of epilepsy system and preliminary results of STN stimulation in animals and humans are reviewed, and alternative mechanisms of seizure suppression by STN stimulation are discussed. PMID- 11779966 TI - An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy. AB - Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable. PMID- 11779967 TI - Network system for automated seizure detection and contingent delivery of therapy. AB - The authors describe an integrated bedside system for real-time seizure detection and automated delivery of electrical stimulation directly to the brain of subjects undergoing invasive epilepsy surgery evaluation. These stimulations were triggered by specific detections following a prespecified pattern. The system uses a commercially available EEG unit, two personal computers, two Grass S-12 stimulators, and other custom-built units to enable interfacing between these components. To date, more than 9,500 hours of electrocorticographic data have been acquired, displayed, and analyzed, and more than 900 closed-loop stimulations for seizure blockage have been delivered safely and reliably to eight subjects with intractable epilepsy. This system generates on-line reports containing information about seizures that provide the epileptologist with timely, valuable data while allowing adaptation of the algorithm detection parameters to improve its performance if necessary. Additionally, it can control the output of any therapeutic device and administrate automatically cognitive tests or radioactive tracers for neuroimaging purposes. This network system, which can be replicated at a relatively low cost by others, is proof of concept for a portable or implantable device that could serve identical functions. Widespread availability of this type of system will advance the fields of clinical and basic epilepsy rapidly and considerably. PMID- 11779968 TI - Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue. AB - How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network. PMID- 11779969 TI - Mechanical stimulation of the fingertip can induce bursts of beta oscillations in sensorimotor areas. AB - Short mechanical stimulation of the fingertip was studied in 10 subjects using 34 closely spaced EEG electrodes overlying sensorimotor areas. The tactile skin stimulation device consisted of a dot matrix printer head. Each stimulus lasted 10 msec with an interstimulus interval of 4 seconds. Tactile stimulation induced beta oscillations, which were largest in the 16 to 20-Hz band, with a maximum centered within 1 second after stimulation. These beta oscillations were found over both hemispheres with a clear dominance over the contralateral hand representation area. PMID- 11779970 TI - Periodic lateralized epileptiform discharges after complex partial status epilepticus associated with increased focal cerebral blood flow. AB - Periodic lateralized epileptiform discharges (PLEDs) are typically associated with encephalitis, cerebral abscess, cerebral infarct, and status epilepticus. There is considerable debate as to whether this pattern is ictal or interictal when seen in association with status epilepticus. We present a patient with complex partial status epilepticus who developed PLEDs and remained comatose despite optimal drug therapy. Technetium 99m single-photon emission computed tomography (SPECT) showed hyperperfusion that resolved with further aggressive antiepileptic drug therapy, indicating that this pattern may indeed be ictal. Further studies are needed to define the significance of PLEDs in patients with status epilepticus. The role of SPECT in differentiating PLEDs as an interictal or ictal pattern also requires further study. PMID- 11779971 TI - The diagnostic value of EEG in Alzheimer disease: correlation with the severity of mental impairment. AB - The aim of our study was to analyze EEG changes in patients with Alzheimer disease (AD) and to determine how closely EEG reflects the progression of mental impairment in people with AD. Ninety-five patients with probable AD according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria treated in our Clinic for Memory Disorders were selected for this study. Patients were divided into three subgroups with mild, marked, and severe dementia according to the results of psychometric scales. The EEG findings were classified using an eight-degree scale according to the background activity, presence and amount of theta and delta waves, focal changes, lateralization of focal changes, synchronization, and presence of sharp and spike waves. A significant correlation between the degree of EEG abnormalities and cognitive impairment was found. We did not observe any correlation between the presence of delta waves and the results of neuropsychological tests. Our study revealed an important diagnostic value of EEG in the estimation of the severity of dementia parallel to psychometric scales. PMID- 11779972 TI - Decrement of N20 amplitude of the median nerve somatosensory evoked potential in Creutzfeldt-Jakob disease patients. AB - We studied somatosensory evoked potentials (SSEPs) in eight Creutzfeldt-Jakob disease (CJD) patients presenting with subacute progressive dementia, generalized myoclonus, and characteristic periodic sharp wave complexes in EEG. Somatosensory evoked potentials were elicited by median nerve stimulation at the wrist. We compared SSEP findings with EEG and the clinical stage proposed by the Japanese Slow Virus Infection Research Committee (stage 1: early stage to stage 5: terminal stage). Until clinical stage 3, short-latency SSEPs showed normal findings despite the severely abnormal EEG. With the progression to clinical stages 4 and 5, however, the amplitude of N20 began to decrease and finally disappeared without prolongation of the latency of N20, whereas other short latency components were preserved. We recorded giant SSEPs in two of three patients in stage 4, when the periodic sharp wave complex in EEG began to decrease in amplitude. The giant SSEPs decreased in amplitude with the progression of the illness. These findings suggest that the short-latency SSEP is relatively preserved until the middle phase of the disease but that it is eventually affected in the terminal phase. We conclude that our results are compatible with the CJD pathologic findings and that the amplitude of N20 reflects the extent of cortical damage in CJD patients. PMID- 11779973 TI - Equiluminant red-green and blue-yellow VEPs in multiple sclerosis. AB - The primate visual system is composed by two color-opponent pathways--red-green (R-G) and blue-yellow (B-Y)--subserved by the so-called parvo- and koniocellular streams respectively. The authors' aim was to compare the relative involvement of chromatic visual subsystems in multiple sclerosis (MS). In 30 MS patients with different forms of MS they recorded visual evoked potentials (VEPs) to onset (300 msec) and offset (700 msec) of equiluminant R-G and B-Y sinusoidal gratings of different contrast (90% and 25%). Equiluminance was established psychophysically by establishing the R-G and the B-Y color ratio at which chromatic gratings alternating at 15 and 10 Hz respectively had minimum visibility. The negative wave at stimulus onset with a peak latency of 120 to 160 msec was evaluated. Ordinary VEPs to luminance (LUM) contrast (black-white reversing checkerboards of 15' check size and 50% contrast) were also recorded for comparison. Latencies of R-G VEPs were abnormal in 53.3% and 58.3% of patients at 90% and 25% contrast respectively, whereas abnormal B-Y VEPs were 56.6% and 48.3%. Latencies of LUM VEPs were abnormal in 45% of patients. Interocular latency asymmetries were abnormal in 59.2% and 33.3% of patients for R-G, and 51.8% and 62.9% for B-Y. Latency asymmetries for LUM VEP were abnormal in 46.4% of patients. The higher rate of VEP abnormalities found with equiluminant chromatic stimuli compared with achromatic stimuli confirms the general vulnerability of color-opponent visual pathways in MS, even if the number of patients with abnormal findings was not significantly different when both test conditions were compared. VEPs to R-G and B-Y equiluminant stimuli appear to be involved approximately to the same extent. PMID- 11779974 TI - The last word. PMID- 11779975 TI - [Smoking-related infiltrative diseases of the lung. Pictorial essay]. PMID- 11779976 TI - [Evaluation of tracheobronchial lesions with spiral CT: comparison between virtual endoscopy and bronchoscopy]. AB - INTRODUCTION: The aim of this study is to describe the scanning parameters for virtual bronchoscopy in the evaluation of the tracheobronchial tree and to compare the results of this examination with the endoscopic findings. MATERIAL AND METHODS: 27 patients with tracheobronchial neoplasms suspected at preliminary clinical and chest film findings or postoperative follow-up for malignant disease were evaluated with spiral CT of the chest and bronchoscopy. Virtual endoscopy was performed on the pulmonary volume involved by the lesion, using narrow axial images (thickness 2 mm, table index 3 mm, reconstruction index 1 mm.) so as to obtain MPR, MIP and 3D reconstructions with 3D Endo Vew program (Philips Medical System, Eindhoven, Holland). We compared these reconstructions and the findings the normal spiral CT scanning with the corresponding endoscopic examinations. RESULTS: In all patients we were able to study the lobar and segmental bronchi in all patients and in 2 we also evaluated the subsegmental bronchi. 25 lesions in 23 patients were shown by virtual endoscopy (8 occlusions, 8 stenosis, 5 compressions, 3 flogosis with endobronchial mucus, 1 bronchocele) and in 4 patients the examinations were negative. The bronchoscopy was negative in 4 patients and positive in 23 patients with 25 lesions, but we had agreement in 23/27 patients (85,1%). In 2 patients virtual endoscopy showed the lesions in a different bronchus compared to bronchoscopy. In one patient we interpreted the obstruction as neoplastic instead of mucus inside the bronchi and in the last patient bronchoscopy was not performed due to his old age and the virtual endoscopy showed total obstruction of a segmental bronchus. DISCUSSION AND CONCLUSIONS: The results show that virtual endoscopy can study the tracheobronchial tree as far as the segmental bronchi, and sometimes also the subsegmental bronchi and the bronchi below a closed obstruction. In addition, it can evaluate the extraluminal location of the lesions. For these reasons virtual endoscopy provides a road map for bronchoscopy as a guide for transbronchial biopsy and for endobronchial treatment planning. The limitation of this technique is its inability to evaluate the mucosal surface and distinguish flogosis from neoplastic lesions by biopsy. It can be used however in the postoperative follow up both for cancer and transplant, when immediate biopsy is not necessary. PMID- 11779977 TI - [Helical CT as preferred imaging modality in the diagnosis of pulmonary embolism]. AB - PURPOSE: We investigated the role of Helical Computed Tomography (CT) as primary screening imaging modality in the diagnosis of pulmonary embolic disease. MATERIAL AND METHODS: We retrospectively reviewed the CT examinations, resulted positive for pulmonary embolism, performed in 134 patients (69 men and 65 women, ranging in age 23-83 years) from June 1998 to June 1999. CT was performed with a helical unit (thickness 3 mm, reconstruction interval 2 mm, pitch 1.5) after intravenous contrast agent (120 mL) rapid infusion (4 mL/s, 15s acquisition delay from bolus starting) and using a power injector. The spiral acquisition was performed from the apex of the pulmonary trunk to the diaphragm. Pulmonary embolism was considered as complete when a filling defect was present in a main pulmonary artery, as moderate when a filling defect was observed in an interlobar pulmonary artery and as very small when a filling defect was identified in a segmental pulmonary artery. RESULTS: Helical CT allowed us to identify the presence of a filling defect in the main pulmonary artery in 60.4% of cases (complete pulmonary embolism), in an interlobar pulmonary artery in 27.6% of cases (moderate pulmonary embolism) and in a segmental pulmonary artery in 11.9% of cases (very small pulmonary embolism). At helical CT study, pulmonary embolus was identified as complete filling defect (92.5% of cases), thromboembolic mass floating freely in the lumen (28.3%) and partial filling defect (19.4%). Pleural effusion and pulmonary infarction were associated in 46.2% and 20.1% respectively. DISCUSSION AND CONCLUSIONS: Pulmonary embolic disease continues to be a major cause of morbidity and mortality. The clinical diagnosis of pulmonary embolism remains an important challenge: among the different imaging modalities, contrast-enhanced helical CT can be used as primary screening imaging modality in the diagnosis of pulmonary embolism, allowing us to detect the presence of pulmonary embolus in the main, lobar and segmental artery, as demonstrated in our experience. PMID- 11779978 TI - [Correlation between computed tomography and isokinesis in patients with reconstructive surgery of anterior cruciate ligament of the knee]. AB - AIM: The aim of this study was to correlate the length (measured by computed tomography) of the anterior cruciate neoligament following knee surgery with the time required by the flexors-extensors of the knee to reach isokinesis (measured using an isokinetic method). MATERIAL AND METHODS: Twenty-five patients (all males, median age 25.4 years), who had undergone surgical repair of the anterior cruciate ligament (ACL), were assessed by computed axial tomography (CT) and isokinetic tests a mean of 6.3 months after their operation. The following isokinetic parameters were calculated: time to reach isokinesis in flexion, time to reach isokinesis in extension, flexion strength, and extension strength. Mean values were calculated from all the values recorded during the test cycles performed. The CT examinations, after lateral scanograms, were carried out with 1 mm contiguous axial scans parallel to the tibial plate. It was possible to assess the integrity of the neoligament which was measured from a section of the tibial plate above the tibial cartilage to its insertion in the intercondylar furrow. RESULTS: As expected, all the values recorded from the healthy knee were significantly different from those recorded on the operated side. As far as concerns analysis of any correlations, there were good correlations between the time to reach isokinesis in extension and the length of the ACL both on the operated side (r=.62) and the healthy side (r=.69), whereas the correlations between the length of the ACL and all other measurements were moderate or very weak (from 0.44 to 0.03). DISCUSSION AND CONCLUSIONS: That the isokinetic measurements show an increased time for the extensor muscles of the operated knee to reach isokinesis is related to altered biomechanics of the passage of the tibia from a posterior translaction position to one of an anterior translaction that is, to anterior displacement of the tibia during extension of the knee, which leads to the prolonged time. The correlation between this time and the length of the ACL, as measured by CT, offers the possibility of being able to monitor the outcome of cruciate ligament repair periodically during various phases of rehabilitation treatment and of only using control CT examinations if there are any complications and/or problems. PMID- 11779979 TI - [Percutaneous radio-frequency ablation of osteoid osteoma: technique and preliminary results]. AB - PURPOSE: To report our personal experience with the percutaneous technique for in situ destruction of osteoid osteoma using radio-frequency ablation. MATERIAL AND METHODS: From January 2000 to January 2001 we performed 16 radio-frequency ablations in 15 patients. All candidates for treatment had previously undergone clinical and radiologic examinations to confirm features typical of osteoid osteoma. After administration of spinal anesthetic, procedures were performed with CT-guidance, using a Kirschner wire introduced into the localized lesion, and a guiding cannula. A hole was first cut into the bone with a cutter, then a few biopsy specimens were obtained with a Jamshidi needle. Finally, we introduced a small radio-frequency electrode into the bone, through the biopsy track. Sufficient current was used to heat the electrode tip to 85-90 degrees C with consequent thermal necrosis of the tissue. The healing was continued for 6 minutes. RESULTS: All patients well tolerated the percutaneous procedure and only 1 underwent a second, successful radio-frequency ablation. In all cases, pain relief was noted to occur very rapidly and all patients could bear full weight on the treated extremity within 24 hours after the procedure. No late complications attributable to the ablation were noted, except for a small eschar next to the puncture site. DISCUSSION AND CONCLUSIONS: The results of the present study suggest that percutaneous ablation is preferred to operative excision because it generally requires shorter hospital stay and is not associated with complications. Furthermore, in our experience, pain relief was noted to occur very rapidly in 100% of cases. In agreement with the literature data, our results show that CT-guided percutaneous radio-frequency ablation can actually replace operative excision in the treatment of osteoid osteoma as it achieves the same clinical outcomes with significantly lower costs. PMID- 11779980 TI - [Pain and anxiety related to mammography in breast cancer patients. Psychological evaluation in an experimental study]. AB - PURPOSE: Previous research focusing on one-time screening rather than repeat adherence, have largely pointed out that anxiety levels and pain expectation are the most common factors which may act as a barrier to mammography. These studies also show that anxiety pain and depression are very often associated with the experience of mammography. The aim of this study was to evaluate whether a supportive psychological intervention can be effective in reducing these feelings in patients undergoing follow-up mammography MATERIAL AND METHODS: The study was performed on 60 women who had already received a diagnosis of breast cancer. In order to detect the variables of depression, anxiety and pain before and after mammography the following questionnaires were administered to the patients: State Trait Anxiety Inventory (STAI), Self-rating Depression Scale (SDS), Visual Analog Scale (VAS). RESULTS AND CONCLUSION: The results of this study show that our psychological intervention significantly lowered the levels of state anxiety and pain but it had no effect on depression. A psychological approach giving patients both emotional and informational support about the examination, may significantly reduce state anxiety levels and the pain felt during mammography. PMID- 11779981 TI - [Current role of color Doppler ultrasound in acute renal failure]. AB - Acute Renal Failure (ARF) is characterized by a rapid decline of the glomerular filtration rate, due to hypotension (prerenal ARF), obstruction of the urinary tract (post-renal ARF) or renal parenchymal disease (renal ARF). The differential diagnosis among different causes of ARF is based on anamnesis, clinical symptoms and laboratory data. Usually ultrasound (US) is the only imaging examination performed in these patients, because it is safe and readily available. In patients with ARF gray scale US is usually performed to rule out obstruction since it is highly sensitive to recognize hydronephrosis. Patients with renal ARF have no specific changes in renal morphology. The size of the kidneys is usually normal or increased, with smooth margins. Detection of small kidneys suggests underlying chronic renal pathology and worse prognosis. Echogenicity and parenchymal thickness are usually normal, but in some cases there are hyperechogenic kidneys, increased parenchymal thickness and increased cortico medullary differentiation. Evaluation of renal vasculature with pulsed Doppler US is useful in the differential diagnosis between prerenal ARF and acute tubular necrosis (ATN), and in the diagnosis of renal obstruction. Latest generation US apparatus allow color Doppler and power Doppler evaluation of renal vasculature up to the interlobular vessels. A significant, but non specific, reduction in renal perfusion is usually appreciable in the patients with ARF. There are renal pathologic conditions presenting with ARF in which color Doppler US provides more specific morphologic and functional information. In particular, color Doppler US often provides direct or indirect signs which can lead to the right diagnosis in old patients with chronic renal insufficiency complicated with ARF, in patients with acute pyelonephritis, hepatic disease, vasculitis, thrombotic microangiopathies, and in patients with acute thrombosis of the renal artery and vein. Contrast enhanced US is another useful diagnostic tool in patients with ARF which has been recently introduced in clinical practice. Microbubble administration may reduce technical failure in the evaluation of the renal artery. Moreover, perfusion defects due to stenosis or thrombosis of the renal segmentary vessels are better recognized. New diagnostic possibilities of enhanced US include evaluation of both cortical and medullar vessels, and functional evaluation of renal perfusion. Measuring the transit time of the microbubbles is useful for the diagnosis of renal artery stenosis and, in transplanted kidneys, for differential diagnosis between ATN and acute rejection. PMID- 11779982 TI - [CT angiography for the evaluation of adult orthotopic liver transplantation arterial complications]. AB - PURPOSE: In this study we compared duplex Doppler sonography, conventional angiography and CT angiography for the evaluation of hepatic arterial complications following orthotopic liver transplantation (OLT). MATERIAL AND METHODS: CT angiography, with Maximum Intensity Projection (MIP) and Volume Rendering reconstructions, was performed in 11 patients with well-grounded suspect of hepatic artery stenosis or thrombosis after routine duplex Doppler examination. Eight patients underwent conventional angiography. RESULTS: CT detected three out of four duplex doppler false positives and confirmed the diagnostic suspect in four cases. In two cases it showed a shift of the blood flow towards the splenic artery with hepatic hypoperfusion. In one case a wrong delay rendered the study unuseful. In seven out of eight patients conventional angiography confirmed CT angiography findings. DISCUSSION. The follow up of OLT arterial complications is now performed with duplex doppler sonography; this technique has a satisfactory sensitivity and specificity, but far from 100%. Therefore in some patients the diagnosis of arterial obstruction might be delayed, with the risk of serious complications; in other cases with ultrasonographic false positive findings, useless angiographic examinations are performed. In our experience CT angiography proved to be a precious tool, which might be included in the diagnostic algorithm of arterial complications after OLT. Particularly CT angiography seems to be suitable for the cases of discordance between clinical and duplex doppler findings, to improve the overall diagnostic accuracy. CONCLUSION: In our experience CT-angiography proved to be accurate and satisfactory as a second step examination after duplex-doppler in the diagnostic algorythm of adult OLT arterial complications. PMID- 11779983 TI - [Role of high resolution color-Doppler US of the sentinel node in patients with stage I melanoma]. AB - PURPOSE: The aims of the present work are to assess the diagnostic accuracy of high resolution color Doppler ultrasound (US) of the sentinel node (SN) in patients with cutaneous melanoma skin at stage I. The US findings of nodal involvement could spare the patient a surgical step (selective lymphaderectomy) allowing them to undergo radical lymphadenectomy directly. MATERIAL AND METHODS: From November 1998 to November 2000 94 patients (mean age 52.7 years) underwent lymphoscintigraphy in order to mark the SN site on their skin. An US scan (112 lymphatic basins) was performed within 24 hours with a 10-13 MHz electronic linear probe with color-power-Doppler (Esaote AU5 Idea Scanner, Genoa, Italy). The sonographic features we analysed were: shape (roundness index), hilum displacement, intranodal heterogenicity, eccentric cortical thickness, extranodal invasion, vessel irregularity. RESULTS: 26 nodes showed US findings consistent with malignant involvement, 86 were negative. All the nodes were surgically removed and controlled by histology. Sensitivity and specificity of US scanning were 89.4% and 90.3%, the positive and negative predictive values 65.3% and 97.6%, respectively. US correctly identified the involved SN in 15,1% cases, so that 17 patients could have avoided the selective lymphadenectomy CONCLUSION: Preoperative lymphoscintigraphy and high-resolution color-Doppler US scanning constitute a useful diagnostic tool in identifying the metastatic SN, with a low margin of error. False negatives were technically induced, even using the more recent scanners, by the low US probe resolution, unable to recognise metastatic microdeposits. The two most reliable parameters in identifying involved lymphnodes were the roundness index and the absence of hilar echo. The advent of technologically more advanced probes should allow better spatial resolution and assessment of lymph node vascularization, enabling diagnosis of metastasis measuring less than 2 mm in diameter. PMID- 11779984 TI - [Doppler evaluation of thyroid hemodynamics after intravenous administration of contrast media]. AB - PURPOSE: Duplex Doppler ultrasound allows the evaluation of thyroid gland vascular flow by spectral analysis assessment. The objective of this prospective study was to employ Doppler ultrasound to evaluate the possible functional changes produced in normal subjects following intravenous iodized contrast medium injection. MATERIAL AND METHODS: The study was performed on 30 non-consecutive subjects, enrolled according to some inclusion criteria: male gender, age ranging between 19 and 70 years, absence of chronic liver disease, absence of thyroid disease, absence of sonographic changes in the thyroid gland, negative history for recent intravenous contrast medium administration. All patients were scheduled for a contrast-enhanced CT study. A non-ionic contrast medium (iomeprol) was employed at 350 mgI/mL concentration, 130-140 mL volume, and 2-4 mL/sec. injection rate. The Doppler ultrasound examination was carried out immediately before and about 30 minutes after the CT study. The systolic velocity, diastolic velocity, the resistive index, and the pulsatility index were measured at the level of one of the four thyroid arteries. RESULTS: In most cases a slightly increasing trend of the four parameters considered was noted but none of these showed a statistically significant change. The mean systolic velocity was of 33 cm/sec. in the basal measurement and of 39 cm/sec. in the post-contrast measurement. The variation was positive in 17 cases, negative in 12, and absent in 1. The mean diastolic velocity was of 13 cm/sec. in the pre-contrast evaluation and of 14 cm/sec. in the second evaluation. The change was positive in 14 cases, negative in 12, and absent in 4. The mean resistive index was of 0.55 in the basal analysis and of 0.59 in the post-contrast one. The variation was positive in 20 patients, negative in 9, and absent in 1. The mean pulsatility index was of 0.99 in the basal measurement and of 1.14 in the second measurement. The change was positive in 23 subjects, negative in 5, and absent in 2. CONCLUSION: Our series shows that no significant change in Doppler spectral analysis of thyroid flow is evident after administration of iodized contrast media, at least in euthyroid subjects and with the contrast doses and the examination intervals employed in our study. Doppler ultrasound is confirmed as an accurate and objective procedure in the evaluation of thyroid gland flow and may represent a useful tool in functional studies, as well as clinical applications in the assessment of thyroid gland disorders. PMID- 11779985 TI - [Treatment of intermetatarsal neuromas with alcohol injection under US guide]. AB - PURPOSE: The cause of intermetatarsal neuromas is unclear; the pathogenesis is, most likely, a mechanically induced degenerative neuropathy or an entrapment of the intermetatarsal nerve under the transverse intermetatarsal ligament. Treatment of intermetatarsal neuromas includes very simple methods, such as changing shoe styles, or more complex conservative treatments such as orthotic devices and steroid injections until surgical therapy. This study aimed to evaluate the neuroma's intralesional treatment with alcohol sclerosing injection as a viable alternative to steroid injections or surgery in persisting symptoms. MATERIAL AND METHODS: 23 patients with clinical symptoms of intermetatarsal neuroma and who had not undergone other treatments were treated with 30% alcohol applied under US guide. Each patient received from 3 to 7 applications at 7 to 10 day intervals. RESULTS: We performed 3 applications in 17 patients, 5 in 5 patients and 7 in 1 patient for a total of 83 applications with a technical success of 100%. A complete resolution of all symptoms was achieved in 91% of the patients. CONCLUSION: Alcohol sclerosing intralesional treatment under US guide is a viable alternative to conservative or surgery treatments in patients with intermetatarsal neuromas. PMID- 11779986 TI - [Endovascular repair of abdominal aortic aneurysm: helical CT findings]. AB - Endovascular repair of infrarenal abdominal aortic aneurysms is currently widely diffuse. Imaging plays a major role in the preprocedural patient evaluation, implantation of stent-graft, and patient follow-up. The aim of this paper is to describe the more frequent findings that can be seen in CT examinations after endovascular repair of infrarenal abdominal aortic aneurysm. We discuss CT findings related to the aneurysm (size, exclusion with complete perigraft thrombosis, back-filling of aneurysm sac via branch vessels) and to the device (dislocation, rotation, kinking, device expansion, patency/thrombosis, device disruption). We also show some examples of incorrect assembly of the modular components of the stent-graft. PMID- 11779987 TI - [Use of a trans-brachial access during percutaneous treatment of abdominal aortic aneurysms]. AB - PURPOSE: To evaluate the utility of a trans-brachial access during percutaneous treatment of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: Since September 1998, 43 patients with AAA, have been treated using different types of endoprosthesis. A right trans-brachial access was performed in each patient to facilitate catheterization of the controlateral iliac limb and to make the advancement of the aortic device easier and safer. Moreover an angiographic catheter was positioned at renal arteries through the trans-brachial access. Then several angiographic controls were performed to check if the position of the endoprosthesis was correct. The catheterization of the iliac stump was performed using the retrograde technique in 31 cases (72%) and the anterograde one in 12 cases (27.9%). RESULTS: The percutaneous trans-brachial access was performed successfully in 42/43 patients. Only one case required surgical exposure. The procedure time for the trans-brachial access ranged from 2-12 min (mean 4.5). Trans-brachial access proved extremely useful in facilitating the aortic device advancement when the iliac-femoral axis was sharply angulated. This access allowed an easier catheterization of controlateral iliac limb. It also permitted several angiographic controls to check the correct position of the endoprosthesis. No pseudoaneurysms, no oculo-cerebral disease, no ischemic phenomena were observed during a 29 month follow-up. Only in 2 cases (4.6%) a small hematoma was noticed the day after the procedure. CONCLUSIONS: Trans brachial access proved to be safe and useful during stent-graft positioning. PMID- 11779988 TI - [Evaluation of patient doses in interventional radiology]. AB - PURPOSE: To verify the suitability of indicative quantities to evaluate the risk related to patient exposure, in abdominal and vascular interventional radiology, by the study of correlations between dosimetric quantities and other indicators. MATERIAL AND METHODS: We performed in vivo measurements of entrance skin dose (ESD) and dose area product (DAP) during 48 procedures to evaluate the correlation among dosimetric quantities, and an estimation of spatial distribution of exposure and effective dose (E). To measure DAP we used a transmission ionization chamber and to evaluate ESD and its spatial distribution we used radiographic film packed in a single envelope and placed near the patient's skin. E was estimated by a calculation software using data from film digitalisation. RESULTS: From the data derived for measurements in 27 interventional procedures on 48 patients we obtained a DAP to E conversion factor of 0.15 mSv / Gy cm2, with an excellent correlation (r=.99). We also found a good correlation between DAP and exposure parameters such as fluoroscopy time and number of images. The greatest effective dose was evaluated for a multiple procedure in the hepatic region, with a DAP value of 425 Gy cm2. The greatest ESD was about 550 mGy. For groups of patients undergoing similar interventional procedures the correlation between ESD and DAP had conversion factors from 6 to 12 mGy Gy-1 cm-2. CONCLUSION: The evaluation of ESD and E by slow films represents a valid method for patient dosimetry in interventional radiology. The good correlation between DAP and fluoroscopy time and number of images confirm the suitability of these indicators as basic dosimetric information. All the ESD values found are lower than threshold doses for deterministic effects. PMID- 11779990 TI - [Hydatid pulmonary embolism. A case report]. PMID- 11779989 TI - [Comparison between estimates of radiological workload]. AB - OBJECTIVE: To comparise three methods for assessing the productivity of radiological services: a) simple count of radiological examinations, b) method proposed by SNR-SAGO-SIRM, c) method used by Regione Emilia Romagna (RER) to evalutate the characteristics of these methods and to find a common method of estimate. MATERIAL AND METHODS: On the radiological examinations performed at our unit over a period of 12 months were recorded. The different types of examinations were clustered into five homogenous groups (general radiology, ultrasound, barium examinations, CT, MRI). The data were assessed by a) number of examinations/hour per radiologist, b) score/hour according to the SNR-SAGO-SIRM method and c) score/hour according to the RER method, and then compared for the percentage of the single aggregates. RESULTS: a) The total number of examinations was 26,776 with 40% being accounted for by general radiology; mean numbers of examinations our ranged from 2.43 (August) to 4.20 (March). b) The total score according to the SNR-SAGO-SIRM method was 67,054. The radiologist weight per hour ranged from 6.37 (August) to 9.67 (May). Ultrasound was the most relevant examination in the unit accounting for 43% of total weight. c) The total score according to the RER method was 1,850,780. The radiologist weight per hour ranged from 159 (August) to 316 (April). CT was the most relevant examination (51% of total weight). CONCLUSION: According to the simple count of examinations, general radiology and ultrasound were the most relevant examinations together accounting for 75% of examinations, i.e. 40% and 35% respectively, whereas by SNR-SAGO-SIRM standards the two techniques represent 19% and 45% respectively. The simple count method therefore fails to give adequate weight to technologically advanced imaging technique. The SNR-SAGO-SIRM method adequately takes into account the combination of patient-number and patient weight. The RER method gives excessive weight costly technology as it considers the total weight of the examination and not only the radiologist's activity. PMID- 11779991 TI - [Traumatic rupture of the diaphragm with particular intra-thoracic dislocation of the liver]. PMID- 11779992 TI - [Intracystic papillary carcinoma of the breast: mammographic, pneumocystographic, sonographic, power-Doppler and MR appearance: a case report]. PMID- 11779993 TI - [Integrated imaging of gastrointestinal stromal tumor (GIST) of the jejunum. A case report]. PMID- 11779994 TI - [Rectum lipoma: CT diagnosis in a case with intestinal occlusion]. PMID- 11779995 TI - [CT findings in a case of glucagonoma with necrolytic migrating erythema]. PMID- 11779996 TI - [Acute portal vein thrombosis treated with locoregional fibrinolysis: a case report]. PMID- 11779997 TI - [Computed Tomography findings in blunt gallbladder trauma: report of two cases]. PMID- 11779998 TI - [Abdominal sarcoidosis: report of two cases]. PMID- 11779999 TI - [Magnetic resonance diagnosis of lipoma of the heel of Milgram's type I: a case report]. PMID- 11780000 TI - Palliative care: a way of thinking, a prescription for doing. PMID- 11780001 TI - Palliative care nursing: ensuring competent care at the end of life. AB - Major advances in enabling function and symptom management have occurred in the past decade. Older adults who would have been bed-bound at the end of life now can be offered interventions to help them live well until they die. People who once would have suffered from pain can expect to be kept comfortable with aggressive symptom management. Palliative care nursing is the art and science of quality end-of-life care. Appropriate interventions for competent palliative care often are not initiated for dying older adults and their families. Nursing professionals are beginning to assume leadership roles to ensure that comprehensive, holistic end-of-life care is available to all patients and families experiencing life-threatening progressive illnesses. PMID- 11780002 TI - End-of-life issues. AB - A patient's desire to discuss end-of-life (EOL) choices may be among the most stressful situations for clinicians. Research confirms the importance of discussions between caregivers and patients or their surrogates about options for current and future care. Often, terminally ill patients want to discuss EOL options to avoid undue suffering, pain, and other symptoms and want some reassurance that caregivers can provide effective physical, psychosocial, and spiritual care. Patients often approach nurses first and ask for their assistance before they ask other professionals; they are more likely to ask nurses in home care than in other settings. PMID- 11780003 TI - A support group for nursing assistants: caring for nursing home residents at the end of life. AB - Certified nursing assistants (CNAS) provide the hands-on care to residents in nursing homes, often developing close relationships with those in their care. The current study used a support program model to explore CNAS' feelings, experiences, and needs when caring for the dying. Special attention was given to the experience of caring for residents who opted not to continue life-sustaining treatment. Second, the efficacy of this type of support program for CNAS was examined. Care of the dying elicited complex reactions: most CNAS reported that caring for dying residents can be a very rewarding experience. At the same time, most thought that caring for a dying person is always emotionally draining. Moreover, CNAS said they felt sad and felt stressed at least some of the time when caring for the dying. CNAS participated openly in the discussion and expressed positive feelings about participating in this type of support program. PMID- 11780004 TI - Terminal restlessness in the nursing facility: assessment, palliation, and symptom management. AB - Terminal restlessness, sometimes called agitated delirium, is a common occurrence at the end of life. This type of delirium may appear as thrashing or agitation, involuntary muscle twitching or jerks, fidgeting or tossing and turning, yelling, or moaning. Among older adults, especially those in long-term care situations, the delirium may not appear to be very different from previous episodes observed when the resident experienced an infection, exacerbation of a chronic condition, anxiety, pain, or adverse drug reactions. However, delirium at the end of life is usually multifactorial and exacerbated by the progressive shutdown of multiple body systems. Therefore, the effective management of terminal restlessness requires a different approach than the usual care of residents with delirium. For many nurses, this responsibility means adding new clinical knowledge and skills to their practice inventories. This article provides an overview of terminal restlessness, offers assessment guidelines for older adults in long-term care situations who are dying, and describes comfort and symptom management strategies for these individuals. PMID- 11780005 TI - Transferring dying nursing home residents to the hospital: DON perspectives on the nurse's role in transfer decisions. AB - This qualitative study elicits factors that influence decision-making by nurses about transferring a dying resident from the nursing home to the hospital. Focus groups with directors of nursing (DONs) from long-term care facilities revealed those decisions are influenced by knowledge (or lack thereof) of resident or family preferences, nurse interactions with physicians, nursing home technological and personnel resources, and nurse concerns about institutional liability. DONs can improve transfer decisions by communicating with all parties, clarifying nursing home processes for end-of-life care, and scheduling early and thorough conversations with residents and families about end-of-life care. DONs can implement improvements through staff education on communication issues, rigorous evaluation and performance outcome measures related to patient transfer, and conveyance to staff of the institution's mission and the nursing service's values. PMID- 11780006 TI - Creating a career ladder for nursing assistants in long-term care. AB - This article describes the development, implementation, and evaluation of a career ladder for certified nursing assistants in long-term care. A career ladder is an effective way to maximize the use of unlicensed workers without changing the skill mix (eg, no loss of licensed nursing positions) and allow the licensed nurse more time to perform higher-level clinical tasks, such as assessments, patient education, and documentation. Implementation of an unlicensed worker career ladder also can improve nursing assistant retention. PMID- 11780007 TI - Patricia Hess, PhD, RN, GNP: leader in care of the dying. PMID- 11780008 TI - Does a liquid supplement improve energy and protein consumption in nursing home residents? AB - One popular strategy to improve the acceptance and efficacy of oral liquid supplements in long-term care is dispensing them during the medication pass, although few studies support its effectiveness. This study evaluated the impact of a supplement medication pass program on energy and nutrient consumption and weight in nursing home residents. Findings indicate that residents maintained their prestudy weight and had a 29% decrease in supplement energy intake, a 19% increase in food energy intake, and a 17% decrease in net energy intake (supplement plus food). Supplement and food protein intake remained stable. Over longer periods, this reduced energy consumption could lead to weight loss, so routine monitoring and periodic evaluations of resident intake (both food and supplement) are recommended to ensure residents are receiving and consuming adequate amounts of daily energy and nutrients. PMID- 11780009 TI - Adverse drug effects: new information about an old problem. PMID- 11780013 TI - Time to halt the gravy train. PMID- 11780010 TI - Preventing medication errors in the home. PMID- 11780014 TI - Map data kept under wraps as Pentagon focuses on security. PMID- 11780015 TI - Spain sets sights on fusion facility. PMID- 11780016 TI - Canadian budget cranks up investment in research. PMID- 11780017 TI - Bush turns to Silicon Valley moguls for scientific advice. PMID- 11780018 TI - Planned merger worries Japan's nuclear researchers. PMID- 11780019 TI - EU ministers temper Framework reforms. PMID- 11780020 TI - British research audit may be last of its kind. PMID- 11780022 TI - Science in a changed world. PMID- 11780023 TI - Delivering death in the mail. PMID- 11780024 TI - A world of difference. PMID- 11780025 TI - Under new management. PMID- 11780026 TI - The killing fields. PMID- 11780027 TI - Data, data, everywhere. PMID- 11780028 TI - Down to Earth with a bump. PMID- 11780029 TI - Beware the baited hook of publicity. PMID- 11780030 TI - Dogs won more fame than female colleagues. PMID- 11780041 TI - Sines in terse verse. PMID- 11780031 TI - Industry and evaluation. PMID- 11780042 TI - Blinded by the light. PMID- 11780043 TI - Part three in the book of genes. PMID- 11780044 TI - Damper for bad vibrations. PMID- 11780045 TI - Life's sweet beginnings? PMID- 11780046 TI - Specifying transcription. PMID- 11780048 TI - Deep down at Chicxulub. PMID- 11780050 TI - Endothelin-1 synthesis reduced by red wine. AB - Statistical evidence of reduced coronary heart disease in areas of high wine consumption has led to the widespread belief that wine affords a protective effect. Although moderate drinking of any alcohol helps to reduce the incidence of coronary heart disease, there is no clear evidence that red wine confers an additional benefit. Here we show that red wines strongly inhibit the synthesis of endothelin-1, a vasoactive peptide that is crucial in the development of coronary atherosclerosis. Our findings indicate that components specific to red wine may help to prevent coronary heart disease. PMID- 11780051 TI - Fractals in pixellated video feedback. AB - Video feedback occurs whenever a video camera is directed at a screen displaying the image currently being recorded by the camera. It can be observed in everyday situations, for example at sporting events when a stadium's display screen comes into the camera's view. Here we consider how this simple physical process is affected by the fact that monitors are pixel-based, and show that it can result in stationary fractal patterns such as von-Koch snowflakes and Sierpinski gaskets. PMID- 11780053 TI - Structural basis of water-specific transport through the AQP1 water channel. AB - Water channels facilitate the rapid transport of water across cell membranes in response to osmotic gradients. These channels are believed to be involved in many physiological processes that include renal water conservation, neuro-homeostasis, digestion, regulation of body temperature and reproduction. Members of the water channel superfamily have been found in a range of cell types from bacteria to human. In mammals, there are currently 10 families of water channels, referred to as aquaporins (AQP): AQP0-AQP9. Here we report the structure of the aquaporin 1 (AQP1) water channel to 2.2 A resolution. The channel consists of three topological elements, an extracellular and a cytoplasmic vestibule connected by an extended narrow pore or selectivity filter. Within the selectivity filter, four bound waters are localized along three hydrophilic nodes, which punctuate an otherwise extremely hydrophobic pore segment. This unusual combination of a long hydrophobic pore and a minimal number of solute binding sites facilitates rapid water transport. Residues of the constriction region, in particular histidine 182, which is conserved among all known water-specific channels, are critical in establishing water specificity. Our analysis of the AQP1 pore also indicates that the transport of protons through this channel is highly energetically unfavourable. PMID- 11780052 TI - The DNA sequence and comparative analysis of human chromosome 20. AB - The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes. PMID- 11780054 TI - Carbonaceous meteorites as a source of sugar-related organic compounds for the early Earth. AB - The much-studied Murchison meteorite is generally used as the standard reference for organic compounds in extraterrestrial material. Amino acids and other organic compounds important in contemporary biochemistry are thought to have been delivered to the early Earth by asteroids and comets, where they may have played a role in the origin of life. Polyhydroxylated compounds (polyols) such as sugars, sugar alcohols and sugar acids are vital to all known lifeforms-they are components of nucleic acids (RNA, DNA), cell membranes and also act as energy sources. But there has hitherto been no conclusive evidence for the existence of polyols in meteorites, leaving a gap in our understanding of the origins of biologically important organic compounds on Earth. Here we report that a variety of polyols are present in, and indigenous to, the Murchison and Murray meteorites in amounts comparable to amino acids. Analyses of water extracts indicate that extraterrestrial processes including photolysis and formaldehyde chemistry could account for the observed compounds. We conclude from this that polyols were present on the early Earth and therefore at least available for incorporation into the first forms of life. PMID- 11780055 TI - Experimental realization of Shor's quantum factoring algorithm using nuclear magnetic resonance. AB - The number of steps any classical computer requires in order to find the prime factors of an l-digit integer N increases exponentially with l, at least using algorithms known at present. Factoring large integers is therefore conjectured to be intractable classically, an observation underlying the security of widely used cryptographic codes. Quantum computers, however, could factor integers in only polynomial time, using Shor's quantum factoring algorithm. Although important for the study of quantum computers, experimental demonstration of this algorithm has proved elusive. Here we report an implementation of the simplest instance of Shor's algorithm: factorization of N = 15 (whose prime factors are 3 and 5). We use seven spin-1/2 nuclei in a molecule as quantum bits, which can be manipulated with room temperature liquid-state nuclear magnetic resonance techniques. This method of using nuclei to store quantum information is in principle scalable to systems containing many quantum bits, but such scalability is not implied by the present work. The significance of our work lies in the demonstration of experimental and theoretical techniques for precise control and modelling of complex quantum computers. In particular, we present a simple, parameter-free but predictive model of decoherence effects in our system. PMID- 11780056 TI - A limit on spin-charge separation in high-Tc superconductors from the absence of a vortex-memory effect. AB - There is a long-standing debate about whether spin-charge separation is the root cause of the peculiar normal-state properties and high superconducting transition temperatures of the high-Tc materials. In the proposed state of matter, the elementary excitations are not electron-like, as in conventional metals, but rather the electron 'fractionalizes' to give excitations that are chargeless spin 1/2 fermions (spinons) and charge +e bosons (chargons). Although spin-charge separation has been well established in one dimension, the theoretical situation for two dimensions is controversial and experimental evidence for it in the high Tc materials is indirect. A model with sharp experimental tests for a particular type of separation in two dimensions has recently been proposed. Here we report the results of those experimental tests, placing a conservative upper limit of 190 K on the energy of the proposed topological defects known as visons. There is still debate about the extent to which this experiment can settle the issue of spin-charge separation in the high-Tc copper oxides, because some forms of the separation are able to avoid the need for visons. But at least one class of theories that all predict a vortex-memory effect now are unlikely models for the copper oxides. PMID- 11780058 TI - Striped iron zoning of olivine induced by dislocation creep in deformed peridotites. AB - Deformation of solid materials affects not only their microstructures, but also their microchemistries. Although chemical unmixing of initially homogeneous multicomponent solids is known to occur during deformation by diffusion creep, there has been no report on their chemical zoning due to deformation by dislocation creep, in either natural samples or laboratory experiments. Here we report striped iron zoning of olivine ((Mg,Fe)2SiO4) in deformed peridotites, where the iron concentration increases at subgrain boundaries composed of edge dislocations. We infer that this zoning is probably formed by alignment of edge dislocations dragging a so-called Cottrell 'atmosphere' of solute atoms (iron in this case) into subgrain boundaries during deformation of the olivine by dislocation creep. We have found that the iron zoning does not develop in laboratory experiments of high strain rates where dislocations move too fast to drag the Cottrell atmosphere. This phenomenon might have important implications for the generation of deep-focus earthquakes, as transformation of olivine to high-pressure phases preferentially occurs in high-iron regions, and therefore along subgrain boundaries which would be preferentially aligned in plastically deformed mantle peridotites. PMID- 11780057 TI - Folding-driven synthesis of oligomers. AB - The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control molecular association, catalysis, self replication or other chemical processes. In the case of proteins in particular, the dependence of these functions on the three-dimensional protein conformation is long known and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner, but it remains challenging to design these so-called 'foldamers' so that they are capable of inducing or controlling chemical processes and interactions. Here we show that the stability gained from folding can be used to control the synthesis of oligomers from short chain segments reversibly ligated through an imine metathesis reaction. That is, folding shifts the ligation equilibrium in favour of conformationally ordered sequences, so that oligomers having the most stable solution structures form preferentially. Crystallization has previously been used to shift an equilibrium in order to indirectly influence the synthesis of small molecules, but the present approach to selectively prepare macromolecules with stable conformations directly connects folding and synthesis, emphasizing molecular function rather than structure in polymer synthesis. PMID- 11780059 TI - Horses damp the spring in their step. AB - The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high frequency oscillations in the limb. PMID- 11780060 TI - Maternal control of resting-egg production in Daphnia. AB - Many planktonic organisms produce 'resting' stages when the environmental conditions deteriorate. Like seeds, resting stages can survive unfavourable conditions. The crustacean Daphnia normally reproduces by means of parthenogenetically produced normal, not resting, eggs-but occasionally switches to bisexual reproduction, which results in two resting eggs encased in a robust structure carried on the back of the female. This 'ephippium' is shed with the next moult, and can survive dormant for many years. The induction of resting-egg production requires multiple environmental stimuli, one of them being photoperiod. The switch from production of parthenogenetic eggs to resting eggs in Daphnia has recently been shown to be influenced by a maternal food effect. Here we present evidence that female Daphnia transmit information not only about food but also on photoperiod to their offspring, and influence the production of resting eggs in the next generation. The combined maternal effects can be relevant for the correct timing of resting-egg production-for example, in discriminating between spring and autumn conditions. PMID- 11780062 TI - Dynamic properties of neurons in cortical area MT in alert and anaesthetized macaque monkeys. AB - In order to see the world with high spatial acuity, an animal must sample the visual image with many detectors that restrict their analyses to extremely small regions of space. The visual cortex must then integrate the information from these localized receptive fields to obtain a more global picture of the surrounding environment. We studied this process in single neurons within the middle temporal visual area (MT) of macaques using stimuli that produced conflicting local and global information about stimulus motion. Neuronal responses in alert animals initially reflected predominantly the ambiguous local motion features, but gradually converged to an unambiguous global representation. When the same animals were anaesthetized, the integration of local motion signals was markedly impaired even though neuronal responses remained vigorous and directional tuning characteristics were intact. Our results suggest that anaesthesia preferentially affects the visual processing responsible for integrating local signals into a global visual representation. PMID- 11780061 TI - The genetic architecture of divergence between threespine stickleback species. AB - The genetic and molecular basis of morphological evolution is poorly understood, particularly in vertebrates. Genetic studies of the differences between naturally occurring vertebrate species have been limited by the expense and difficulty of raising large numbers of animals and the absence of molecular linkage maps for all but a handful of laboratory and domesticated animals. We have developed a genome-wide linkage map for the three-spined stickleback (Gasterosteus aculeatus), an extensively studied teleost fish that has undergone rapid divergence and speciation since the melting of glaciers 15,000 years ago. Here we use this map to analyse the genetic basis of recently evolved changes in skeletal armour and feeding morphologies seen in the benthic and limnetic stickleback species from Priest Lake, British Columbia. Substantial alterations in spine length, armour plate number, and gill raker number are controlled by genetic factors that map to independent chromosome regions. Further study of these regions will help to define the number and type of genetic changes that underlie morphological diversification during vertebrate evolution. PMID- 11780063 TI - Noggin and retinoic acid transform the identity of avian facial prominences. AB - The signals that determine body part identity in vertebrate embryos are largely unknown, with some exceptions such as those for teeth and digits. The vertebrate face is derived from small buds of tissue, facial prominences, that surround the embryonic oral cavity. In chicken embryos, the skeleton of the upper beak is derived from the frontonasal mass and maxillary prominences. Here we show that bone morphogenetic proteins (Bmps) and the vitamin A derivative, retinoic acid (RA), are used to specify the identity of the frontonasal mass and maxillary prominences. Implanting two beads adjacent to the stage-15 presumptive maxillary field, one soaked in the Bmp antagonist Noggin and one soaked in RA, induces a duplicate set of frontonasal mass skeletal elements in place of maxillary bones. We also show that the duplicated beak is due to transformation of the maxillary prominence into a second frontonasal mass and not due to ectopic migration of cells or splitting of the normal frontonasal mass. Thus the levels of Bmp and RA determine whether specific regions of the face form maxillary or frontonasal mass derivatives. PMID- 11780064 TI - Gene defect in ectodermal dysplasia implicates a death domain adapter in development. AB - Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins. Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives. Mutations in Edar-or its ligand, Eda-cause hypohidrotic ectodermal dysplasia in humans and mice. This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth. Here we report the identification of a death domain adapter encoded by the mouse crinkled locus. The crinkled mutant has an hypohidrotic ectodermal dysplasia phenotype identical to that of the edar (downless) and eda (Tabby) mutants. This adapter, which we have called Edaradd (for Edar-associated death domain), interacts with the death domain of Edar and links the receptor to downstream signalling pathways. We also identify a missense mutation in its human orthologue, EDARADD, that is present in a family affected with hypohidrotic ectodermal dysplasia. Our findings show that the death receptor/adapter signalling mechanism is conserved in developmental, as well as apoptotic, signalling. PMID- 11780065 TI - Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. AB - Inappropriate or prolonged inflammation is the main cause of many diseases; for this reason it is important to understand the physiological mechanisms that terminate inflammation in vivo. Agonists for several Gs-protein-coupled receptors, including cell-surface adenosine purinergic receptors, can increase levels of immunosuppressive cyclic AMP in immune cells; however, it was unknown whether any of these receptors regulates inflammation in vivo. Here we show that A2a adenosine receptors have a non-redundant role in the attenuation of inflammation and tissue damage in vivo. Sub-threshold doses of an inflammatory stimulus that caused minimal tissue damage in wild-type mice were sufficient to induce extensive tissue damage, more prolonged and higher levels of pro inflammatory cytokines, and death of male animals deficient in the A2a adenosine receptor. Similar observations were made in studies of three different models of inflammation and liver damage as well as during bacterial endotoxin-induced septic shock. We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. PMID- 11780066 TI - MIF regulates innate immune responses through modulation of Toll-like receptor 4. AB - Macrophages are pivotal effector cells of the innate immune system, which is vital for recognizing and eliminating invasive microbial pathogens. When microbial products bind to pathogen-recognition receptors, macrophages become activated and release a broad array of cytokines that orchestrate the host innate and adaptive immune responses. Initially identified as a T-cell cytokine, macrophage migration inhibitory factor (MIF) is also a macrophage cytokine and an important mediator of inflammation and sepsis. Here we report that MIF is an essential regulator of macrophage responses to endotoxin (lipopolysaccharide) and Gram-negative bacteria. Compared with wild-type cells, MIF-deficient macrophages are hyporesponsive to lipopolysaccharide and Gram-negative bacteria, as shown by a profound reduction in the activity of NF-kappaB and the production of tumour necrosis factor-alpha. This reduction is due to a downregulation of Toll-like receptor 4 (TLR4), the signal-transducing molecule of the lipopolysaccharide receptor complex, and is associated with decreased activity of transcription factor PU.1, which is required for optimal expression of the Tlr4 gene in myeloid cells. These findings identify an important role for MIF in innate immunity and provide a molecular basis for the resistance of MIF-deficient mice to endotoxic shock. PMID- 11780067 TI - Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. AB - An array of regulatory protein and multi-subunit cofactors has been identified that directs eukaryotic gene transcription. However, establishing the specific functions of various related cofactors has been difficult owing to the limitations inherent in assaying transcription in animals and cells indirectly. Here we describe, using an integrated chromatin-dependent reconstituted transcription reaction, the purification and identification of a multi-subunit cofactor (PBAF) that is necessary for ligand-dependent transactivation by nuclear hormone receptors. A highly related cofactor, human SWI/SNF, and the ISWI containing chromatin-remodelling complex ACF both fail to potentiate transcription. We also show that transcriptional activation mediated by nuclear hormone receptors requires TATA-binding protein (TBP)-associated factors (TAFs) as well as the multi-subunit cofactors ARC/CRSP. These studies demonstrate functional selectivity amongst highly related complexes involved in gene regulation and help define a more complete set of factors and cofactors required to activate transcription. PMID- 11780068 TI - Stimulatory effect of splicing factors on transcriptional elongation. AB - Transcription and pre-mRNA splicing are tightly coupled gene expression events in eukaryotic cells. An interaction between the carboxy-terminal domain of the largest subunit of RNA polymerase (Pol) II and components of the splicing machinery is postulated to mediate this coupling. Here, we show that splicing factors function directly to promote transcriptional elongation, demonstrating that transcription is more intimately coupled to splicing than previously thought. The spliceosomal U small nuclear ribonucleoproteins (snRNPs) interact with human transcription elongation factor TAT-SF1 (refs 6,7,8,9) and strongly stimulate polymerase elongation when directed to an intron-free human immunodeficiency virus-1 (HIV-1) template. This effect is likely to be mediated through the binding of TAT-SF1 to elongation factor P-TEFb, a proposed component of the transcription elongation complex. Inclusion of splicing signals in the nascent transcript further stimulates transcription, supporting the notion that the recruitment of U snRNPs near the elongating polymerase is important for transcription. Because the TAT-SF1-U snRNP complex also stimulates splicing in vitro, it may serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation. PMID- 11780069 TI - Crystal structure of an Eph receptor-ephrin complex. AB - The Eph family of receptor tyrosine kinases and their membrane-anchored ephrin ligands are important in regulating cell-cell interactions as they initiate a unique bidirectional signal transduction cascade whereby information is communicated into both the Eph-expressing and the ephrin-expressing cells. Initially identified as regulators of axon pathfinding and neuronal cell migration, Ephs and ephrins are now known to have roles in many other cell-cell interactions, including those of vascular endothelial cells and specialized epithelia. Here we report the crystal structure of the complex formed between EphB2 and ephrin-B2, determined at 2.7 A resolution. Each Eph receptor binds an ephrin ligand through an expansive dimerization interface dominated by the insertion of an extended ephrin loop into a channel at the surface of the receptor. Two Eph-Ephrin dimers then join to form a tetramer, in which each ligand interacts with two receptors and each receptor interacts with two ligands. The Eph and ephrin molecules are precisely positioned and orientated in these complexes, promoting higher-order clustering and the initiation of bidirectional signalling. PMID- 11780071 TI - Timely messages for the South. PMID- 11780072 TI - Towards more effective drug discovery. PMID- 11780073 TI - German task force outraged by changes to science fraud report. PMID- 11780076 TI - Future funds in doubt as asteroid project wins short reprieve. PMID- 11780074 TI - Body identified as missing biologist. PMID- 11780077 TI - Online marine resource could soon be swimming with data. PMID- 11780078 TI - Museum staff strike to prevent loss of artefacts. PMID- 11780079 TI - Anthropologists split over misconduct claims. PMID- 11780081 TI - Surviving a knockout blow. PMID- 11780082 TI - The physics of the trading floor. PMID- 11780083 TI - Intuition and inspiration made Gamow a star turn. PMID- 11780084 TI - Postdocs don't need reality to hit so hard. PMID- 11780086 TI - Fruitful synthesis of science and fiction. PMID- 11780085 TI - Talking about regeneration. PMID- 11780087 TI - Standardizing chemical risk assessment, at last. PMID- 11780088 TI - 1902 and all that. PMID- 11780096 TI - Breaking up a superfluid. PMID- 11780095 TI - Geology of mankind. PMID- 11780097 TI - The price of tumour suppression? PMID- 11780098 TI - A baryometer is back. PMID- 11780101 TI - Magnetic bubbles in space. PMID- 11780099 TI - Sounds, signals and space maps. PMID- 11780102 TI - Group effort in toxin synthesis. PMID- 11780104 TI - Seeing through the face of deception. AB - We have developed a high-definition thermal-imaging technique that can detect attempted deceit by recording the thermal patterns from people's faces. This technique has an accuracy comparable to that of polygraph examination by experts and has potential for application in remote and rapid security screening, without the need for skilled staff or physical contact. PMID- 11780105 TI - Expanded niche for white sharks. AB - Until the advent of electronic tagging technology, the inherent difficulty of studying swift and powerful marine animals made ecological information about sharks of the family Lamnidae difficult to obtain. Here we report the tracking of movements of white sharks by using pop-up satellite archival tags, which reveal that their migratory movements, depth and ambient thermal ranges are wider than was previously thought. PMID- 11780106 TI - Mass march of termites into the deadly trap. AB - Carnivorous pitcher plants of the genus Nepenthes are not usually very selective about their prey, catching anything that is careless enough to walk on their slippery peristome, but Nepenthes albomarginata is an exception. We show here that this plant uses a fringe of edible white hairs to lure and then trap its prey, which consists exclusively of termites in enormous numbers. This singular feature accounts for the specialization of N. albomarginata for one prey taxon, unique so far among carnivorous plants. PMID- 11780107 TI - Did Nile flooding sink two ancient cities? AB - The discovery of the two cities of Herakleion and East Canopus under the waters of the Bay of Abu Qir (east of Alexandria, Egypt) stirred worldwide attention when it was first announced in the summer of 2000. Their disappearance some 1,250 years ago has been ascribed by Stanley, Goddio and Schnepp to a strong Nile flood that caused riverbank failure and the destruction of the two cities, rather than to the action of earthquakes, as was first proposed when the ruins were discovered. But I believe that this interpretation is flawed, because no flood could have reached the Abu Qir Bay at the time of the disappearance of the two cities, as the Canopic branch of the Nile, along whose banks they were situated, had dried to a trickle more than 200 years earlier. PMID- 11780108 TI - Atmospheric CO2 from fossil plant cuticles. AB - Plants respond to changes in atmospheric carbon dioxide levels by regulating the number of stomata in their leaves. In his reconstruction of a continuous, 300 million-year record of atmospheric CO2, Retallack bases his curve on stomatal counts of fossil plant cuticles taken from published micrographs. However, the preservation of cuticles from Permian times is generally too fragmentary for the stomatal index to be reliably determined, the micrographs used could have biased the results, and there are important errors in the supplementary data - all of which cast doubt on the Permian part of Retallack's record. PMID- 11780110 TI - Quantum phase transition from a superfluid to a Mott insulator in a gas of ultracold atoms. AB - For a system at a temperature of absolute zero, all thermal fluctuations are frozen out, while quantum fluctuations prevail. These microscopic quantum fluctuations can induce a macroscopic phase transition in the ground state of a many-body system when the relative strength of two competing energy terms is varied across a critical value. Here we observe such a quantum phase transition in a Bose-Einstein condensate with repulsive interactions, held in a three dimensional optical lattice potential. As the potential depth of the lattice is increased, a transition is observed from a superfluid to a Mott insulator phase. In the superfluid phase, each atom is spread out over the entire lattice, with long-range phase coherence. But in the insulating phase, exact numbers of atoms are localized at individual lattice sites, with no phase coherence across the lattice; this phase is characterized by a gap in the excitation spectrum. We can induce reversible changes between the two ground states of the system. PMID- 11780112 TI - The cosmological density of baryons from observations of 3He+ in the Milky Way. AB - Primordial nucleosynthesis after the Big Bang can be constrained by the abundances of the light elements and isotopes 2H, 3He, 4He and 7Li (ref. 1). The standard theory of stellar evolution predicts that 3He is also produced by solar type stars, so its abundance is of interest not only for cosmology, but also for understanding stellar evolution and the chemical evolution of the Galaxy. The 3He abundance in star-forming (H II) regions agrees with the present value for the local interstellar medium, but seems to be incompatible with the stellar production rates inferred from observations of planetary nebulae, which provide a direct test of stellar evolution theory. Here we develop our earlier observations, which, when combined with recent theoretical developments in our understanding of light-element synthesis and destruction in stars, allow us to determine an upper limit for the primordial abundance of 3He relative to hydrogen: 3He/H = (1.1 +/- 0.2) x 10(-5). The primordial density of all baryons determined from the 3He data is in excellent agreement with the densities calculated from other cosmological probes. The previous conflict is resolved because most solar-mass stars do not produce enough 3He to enrich the interstellar medium significantly. PMID- 11780111 TI - p53 mutant mice that display early ageing-associated phenotypes. AB - The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing. PMID- 11780113 TI - Interstellar scintillation as the origin of the rapid radio variability of the quasar J1819+3845. AB - The liberation of gravitational energy as matter falls onto a supermassive black hole at the centre of a galaxy is believed to explain the high luminosity of quasars. The variability of this emission from quasars and other types of active galactic nuclei can provide information on the size of the emitting regions and the physical process of fuelling the black hole. Some active galactic nuclei are variable at optical (and shorter) wavelengths, and display radio outbursts over years and decades. These active galactic nuclei often also show faster intraday variability at radio wavelengths. The origin of this rapid variability has been extensively debated, but a correlation between optical and radio variations in some sources suggests that both are intrinsic. This would, however, require radiation brightness temperatures that seem physically implausible, leading to the suggestion that the rapid variations are caused by scattering of the emission by the interstellar medium inside our Galaxy. Here we show that the rapid variations in the extreme case of quasar J1819+3845 (ref. 10) indeed arise from interstellar scintillation. The transverse velocity of the scattering material reveals the presence of plasma with a surprisingly high velocity close to the Solar System. PMID- 11780114 TI - Mesoscopic superconductor as a ballistic quantum switch. AB - Several key experiments have revealed a rich variety of vortex structures in mesoscopic superconductors in which only a few quanta of magnetic flux are trapped: these structures are polygon-like vortex 'molecules' and multi-quanta giant vortices. Ginzburg-Landau calculations confirmed second-order phase transitions between the giant vortex states and stable molecule-like configurations. Here we study theoretically the electronic structure and the related phase-coherent transport properties of such mesoscopic superconductor systems. The quasiparticle excitations in the vortices form coherent quantum mechanical states that offer the possibility of controlling the phase-coherent transport through the sample by changing the number of trapped flux quanta and their configuration. The sample conductance measured in the direction of the applied magnetic field is determined by the transparency of multi-vortex configurations, which form a set of quantum channels. The transmission coefficient for each channel is controlled by multiple Andreev reflections within the vortex cores and at the sample edge. These interference phenomena result in a stepwise behaviour of the conductance as a function of the applied magnetic field, and we propose to exploit this effect to realize a vortex-based quantum switch where the magnetic field plays the role of the gate voltage. PMID- 11780115 TI - A robust DNA mechanical device controlled by hybridization topology. AB - Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind. PMID- 11780116 TI - Evolutionary speed limits inferred from the fossil record. AB - The dynamics of extinction and diversification determine the long-term effects of extinction episodes. If rapid bursts of extinction are offset by equally rapid bursts of diversification, their biodiversity consequences will be transient. But if diversification rates cannot accelerate rapidly enough, pulses of extinction will lead to long-lasting depletion of biodiversity. Here I use spectral analysis of the fossil record to test whether diversification rates can accelerate as much as extinction rates, over both short and long spans of geological time. I show that although the long-wavelength variability of diversification rates equals or exceeds that of extinctions, diversification rates are markedly less variable than extinction rates at wavelengths shorter than roughly 25 million years. This implies that there are intrinsic speed limits that constrain how rapidly diversification rates can accelerate in response to pulses of extinction. PMID- 11780117 TI - Resource-based niches provide a basis for plant species diversity and dominance in arctic tundra. AB - Ecologists have long been intrigued by the ways co-occurring species divide limiting resources. Such resource partitioning, or niche differentiation, may promote species diversity by reducing competition. Although resource partitioning is an important determinant of species diversity and composition in animal communities, its importance in structuring plant communities has been difficult to resolve. This is due mainly to difficulties in studying how plants compete for below-ground resources. Here we provide evidence from a 15N-tracer field experiment showing that plant species in a nitrogen-limited, arctic tundra community were differentiated in timing, depth and chemical form of nitrogen uptake, and that species dominance was strongly correlated with uptake of the most available soil nitrogen forms. That is, the most productive species used the most abundant nitrogen forms, and less productive species used less abundant forms. To our knowledge, this is the first documentation that the composition of a plant community is related to partitioning of differentially available forms of a single limiting resource. PMID- 11780118 TI - Polyandrous females avoid costs of inbreeding. AB - Why do females typically mate with more than one male? Female mating patterns have broad implications for sexual selection, speciation and conflicts of interest between the sexes, and yet they are poorly understood. Matings inevitably have costs, and for females, the benefits of taking more than one mate are rarely obvious. One possible explanation is that females gain benefits because they can avoid using sperm from genetically incompatible males, or invest less in the offspring of such males. It has been shown that mating with more than one male can increase offspring viability, but we present the first clear demonstration that this occurs because females with several mates avoid the negative effects of genetic incompatibility. We show that in crickets, the eggs of females that mate only with siblings have decreased hatching success. However, if females mate with both a sibling and a non-sibling they avoid altogether the low egg viability associated with sibling matings. If similar effects occur in other species, inbreeding avoidance may be important in understanding the prevalence of multiple mating. PMID- 11780119 TI - The optic tectum controls visually guided adaptive plasticity in the owl's auditory space map. AB - The midbrain contains an auditory map of space that is shaped by visual experience. When barn owls are raised wearing spectacles that horizontally displace the visual field, the auditory space map in the external nucleus of the inferior colliculus (ICX) shifts according to the optical displacement of the prisms. Topographic visual activity in the optic tectum could serve as the template that instructs the auditory space map. We studied the effects of a restricted, unilateral lesion in the portion of the optic tectum that represents frontal space. Here we show that such a lesion eliminates adaptive adjustments specifically in the portion of the auditory map that represents frontal space on the same side of the brain, while the rest of the map continues to adjust adaptively. Thus, activity in the tectum calibrates the auditory space map in a location-specific manner. Because the site of adaptive changes is the ICX, the results also indicate that the tectum provides a topographic instructive signal that controls adaptive auditory plasticity in the ICX. PMID- 11780120 TI - Stage-specific control of neuronal migration by somatostatin. AB - Developing neurons transiently express somatostatin and its receptors, but little is known about their function at these early stages. As we thought that endogenous somatostatin might control the migratory behaviour of immature neurons, we have examined the effects of somatostatin in cerebellar granule cells of early postnatal mice, because these cells express all five types of somatostatin receptors before the initiation of their migration. Here we show that somatostatin has opposite and stage-specific effects on the migration of cerebellar granule cells. Activation of somatostatin receptors increases the rate of granule cell migration near their birthplace, but decreases the rate near their final destination. Furthermore, somatostatin enhances the size and frequency of spontaneous Ca2+ fluctuations in the early phase of migration, whereas it eliminates spike-like Ca2+ transients in the late phase. Somatostatin induced changes at both early and late phases are reversed by a blockade of K+ channel activity. These results indicate that somatostatin may provide an essential cue for accelerating the movement of granule cells in the early phase and for terminating the movement in the late phase through altering intracellular Ca2+ concentrations and K+ channel activity. PMID- 11780121 TI - Inter-receptor communication through arrays of bacterial chemoreceptors. AB - The sensing mechanisms of chemotactic bacteria allow them to respond sensitively to stimuli. Escherichia coli, for example, respond to changes in chemoattractant concentration of less than 10% over a range spanning six orders of magnitude. Sensitivity over this range depends on a nonlinear relationship between ligand concentration and output response. At low ligand concentrations, substantial amplification of the chemotactic signal is required; however, the mechanism responsible for this amplification remains unclear. Here we demonstrate that inter-receptor communication within a lattice acts to amplify and integrate sensory information. Synthetic multivalent ligands that interact through the low abundance, galactose-sensing receptor Trg stabilize large clusters of chemoreceptors and markedly enhance signal output from these enforced clusters. On treatment with multivalent ligands, the response to the attractant serine is amplified by at least 100-fold. This amplification requires a full complement of chemoreceptors; deletion of the aspartate (Tar) or dipeptide (Tap) receptors diminishes the amplification of the serine response. These results demonstrate that the entire array is involved in sensing. This mode of information exchange has general implications for the processing of signals by cellular receptors. PMID- 11780122 TI - Two-component regulator of Enterococcus faecalis cytolysin responds to quorum sensing autoinduction. AB - Bacteria of the genus Enterococcus are the main causes of highly antibiotic resistant infections that are acquired in hospitals. Many clinical isolates of Enterococcus faecalis produce an exotoxin called cytolysin that contributes to bacterial virulence. In addition to its toxin activity, the cytolysin is bactericidal for nearly all Gram-positive organisms. An understanding of conditions that regulate cytolysin expression has advanced little since its initial description. Here we show that the products of two genes, cylR1 and cylR2, which lack homologues of known function, work together to repress transcription of cytolysin genes. Derepression occurs at a specific cell density when one of the cytolysin subunits reaches an extracellular threshold concentration. These observations form the basis of a model for the autoinduction of the cytolysin by a quorum-sensing mechanism involving a two-component regulatory system. PMID- 11780123 TI - Identification of a host protein essential for assembly of immature HIV-1 capsids. AB - To form an immature HIV-1 capsid, 1,500 HIV-1 Gag (p55) polypeptides must assemble properly along the host cell plasma membrane. Insect cells and many higher eukaryotic cell types support efficient capsid assembly, but yeast and murine cells do not, indicating that host machinery is required for immature HIV 1 capsid formation. Additionally, in a cell-free system that reconstitutes HIV-1 capsid formation, post-translational assembly events require ATP and a subcellular fraction, suggesting a requirement for a cellular ATP-binding protein. Here we identify such a protein (HP68), described previously as an RNase L inhibitor, and demonstrate that it associates post-translationally with HIV-1 Gag in a cell-free system and human T cells infected with HIV-1. Using a dominant negative mutant of HP68 in mammalian cells and depletion-reconstitution experiments in the cell-free system, we demonstrate that HP68 is essential for post-translational events in immature HIV-1 capsid assembly. Furthermore, in cells the HP68-Gag complex is associated with HIV-1 Vif, which is involved in virion morphogenesis and infectivity. These findings support a critical role for HP68 in post-translational events of HIV-1 assembly and reveal a previously unappreciated dimension of host-viral interaction. PMID- 11780124 TI - IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. AB - The unfolded protein response (UPR), caused by stress, matches the folding capacity of endoplasmic reticulum (ER) to the load of client proteins in the organelle. In yeast, processing of HAC1 mRNA by activated Ire1 leads to synthesis of the transcription factor Hac1 and activation of the UPR. The responses to activated IRE1 in metazoans are less well understood. Here we demonstrate that mutations in either ire-1 or the transcription-factor-encoding xbp-1 gene abolished the UPR in Caenorhabditis elegans. Mammalian XBP-1 is essential for immunoglobulin secretion and development of plasma cells, and high levels of XBP 1 messenger RNA are found in specialized secretory cells. Activation of the UPR causes IRE1-dependent splicing of a small intron from the XBP-1 mRNA both in C. elegans and mice. The protein encoded by the processed murine XBP-1 mRNA accumulated during the UPR, whereas the protein encoded by unprocessed mRNA did not. Purified mouse IRE1 accurately cleaved XBP-1 mRNA in vitro, indicating that XBP-1 mRNA is a direct target of IRE1 endonucleolytic activity. Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes. PMID- 11780125 TI - Superoxide activates mitochondrial uncoupling proteins. AB - Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria. PMID- 11780126 TI - Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. AB - Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity. Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46. HIPK2 localizes with p53 and PML-3 into the nuclear bodies and is activated after irradiation with ultraviolet. Antisense inhibition of HIPK2 expression reduces the ultraviolet induced apoptosis. Furthermore, HIPK2 and p53 cooperate in the activation of p53 dependent transcription and apoptotic pathways. These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis. PMID- 11780127 TI - The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. AB - The gene strabismus (stbm)/Van Gogh (Vang) functions in the planar cell-polarity pathway in Drosophila. As the existence of such a pathway in vertebrates has not been firmly established, we investigated the functions and signalling activities encoded by stbm in vertebrate embryos. In regard to cell fate, inhibition of Stbm function in zebrafish embryos leads to reduction of anterior neural markers, whereas gain of function leads to a rise in the levels of these markers. In regard to cell behaviour, both gain-of-function and loss-of-function assays reveal a role for Stbm in mediating cell movements during gastrulation. Mechanistically, Stbm inhibits Wnt-mediated activation of beta-catenin-dependent transcription while promoting phosphorylation of c-Jun- and AP-1-dependent transcription. This complex effect on intracellular signalling pathways probably involves dishevelled (dsh), as Stbm was found to interact with the Dsh protein, and as Dsh is known to function in both planar cell-polarity and beta-catenin pathways in Drosophila. PMID- 11780128 TI - Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. AB - Induction of apoptosis of keratinocytes by ultraviolet (UV) radiation is a protective phenomenon relevant in limiting the survival of cells with irreparable DNA damage. Changes in UV-induced apoptosis may therefore have significant impact on photocarcinogenesis. We have found that the immunomodulatory cytokine IL-12 suppresses UV-mediated apoptosis of keratinocytes both in vitro and in vivo. IL 12 caused a remarkable reduction in UV-specific DNA lesions which was due to induction of DNA repair. In accordance with this, IL-12 induced the expression of particular components of the nucleotide-excision repair complex. Our results show that cytokines can protect cells from apoptosis induced by DNA-damaging UV radiation by inducing DNA repair, and that nucleotide-excision repair can be manipulated by cytokines. PMID- 11780129 TI - Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. AB - Fission yeast centromeres, like those of higher eukaryotes, are composed of repeated DNA structures and associated heterochromatin protein complexes, that have a critical function in the faithful segregation of chromosomes during cell division. Cohesin protein complexes, which are essential for sister-chromatid cohesion and proper chromosome segregation, are enriched at centromeric repeats. We have identified a functional and physical link between heterochromatin and cohesin. We find that the preferential localization of cohesins at the centromeric repeats is dependent on Swi6, a conserved heterochromatin protein that is required for proper kinetochore function. Cohesin is also enriched at the mating-type heterochromatic region in a manner that depends on Swi6 and is required to preserve the genomic integrity of this locus. We provide evidence that a cohesin subunit Psc3 interacts with Swi6 and its mouse homologue HP1. These data define a conserved function of Swi6/HP1 in recruitment of cohesin to heterochromatic regions, promoting the proper segregation of chromosomes. PMID- 11780131 TI - Lymphatic endothelium: a new frontier of metastasis research. AB - The vascular endothelium is a dynamic tissue with many active functions. Until recently, endothelial cell (EC) biology studies have used cultured ECs from various organs; these cell lines are considered representative of the blood vascular endothelium. Very few lymphatic EC lines have been available, and these were derived from lymphatic tumours or large collecting lymphatic ducts. In the past, lymphatic vessels were defined largely by the lack of erythrocytes in their lumen, a lack of junctional complexes and the lack of a well-defined basement membrane. Now that lymphatic-specific vascular endothelial growth factors (VEGF-C and VEGF-D) and molecular cell surface markers such as the VEGFR-3 receptor have been identified, this definition needs to be updated. Recent developments have highlighted the importance of lymphatic ECs, and they could become the next focus for angiogenesis and metastasis research. PMID- 11780132 TI - Strabismus comes into focus. PMID- 11780133 TI - A crossbridge too far. PMID- 11780134 TI - Finding the path less followed. PMID- 11780135 TI - Novel effector function for an old receptor. PMID- 11780136 TI - Reach for the stars. PMID- 11780139 TI - Imaging into the future: visualizing gene expression and protein interactions with fluorescent proteins. AB - Since its introduction into heterologous organisms as a marker of gene expression, the green fluorescent protein (GFP) has led a dramatic revolution in cell, developmental and neurobiology. By allowing breathtaking visualization of fluorescent fusion proteins as they move within and between cells, GFP has fundamentally transformed the spatial analysis of protein function. Now, new GFP technologies allow far more than simple observations of fusion protein localization. The growing family of fluorescent protein variants is enabling more sophisticated studies of protein function and illuminating wide-ranging processes from gene expression to second-messenger cascades and intercellular signalling. Together with advances in microscopy, new GFP-based experimental approaches are forging a second GFP revolution. PMID- 11780140 TI - The extent of linkage disequilibrium in Arabidopsis thaliana. AB - Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosomal extent of LD is crucial in this context, because it determines how dense a map must be for associations to be detected and, conversely, limits how finely loci may be mapped. Arabidopsis thaliana is expected to harbor unusually extensive LD because of its high degree of selfing. Several polymorphism studies have found very strong LD within individual loci, but also evidence of some recombination. Here we investigate the pattern of LD on a genomic scale and show that in global samples, LD decays within approximately 1 cM, or 250 kb. We also show that LD in local populations may be much stronger than that of global populations, presumably as a result of founder events. The combination of a relatively high level of polymorphism and extensive haplotype structure bodes well for developing a genome-wide LD map in A. thaliana. PMID- 11780141 TI - Chromosomal silencing and localization are mediated by different domains of Xist RNA. AB - The gene Xist initiates the chromosomal silencing process of X inactivation in mammals. Its product, a noncoding RNA, is expressed from and specifically associates with the inactive X chromosome in female cells. Here we use an inducible Xist expression system in mouse embryonic stem cells that recapitulates long-range chromosomal silencing to elucidate which Xist RNA sequences are necessary for chromosomal association and silencing. We show that chromosomal association and spreading of Xist RNA can be functionally separated from silencing by specific mutations. Silencing requires a conserved repeat sequence located at the 5' end of Xist. Deletion of this element results in Xist RNA that still associates with chromatin and spreads over the chromosome but does not effect transcriptional repression. Association of Xist RNA with chromatin is mediated by functionally redundant sequences that act cooperatively and are dispersed throughout the remainder of Xist but show little or no homology. PMID- 11780144 TI - Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. AB - N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity in the mammalian hippocampus is essential for learning and memory. Although computational models and anatomical studies have emphasized functional differences among hippocampal subregions, subregional specificity of NMDA receptor function is largely unknown. Here we present evidence that NMDA receptors in CA3 are required in a situation in which spatial representation needs to be reorganized, whereas the NMDA receptors in CA1 and/or the dentate gyrus are more involved in acquiring memory that needs to be retrieved after a delay period exceeding a short-term range. Our data, with data from CA1-specific knockout mice, suggest the possibility of heterogeneous mnemonic function of NMDA receptors in different subregions of the hippocampus. PMID- 11780145 TI - Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar. AB - We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus. PMID- 11780146 TI - Structure of the Bcr-Abl oncoprotein oligomerization domain. AB - The Bcr-Abl oncoprotein is responsible for a wide range of human leukemias, including most cases of Philadelphia chromosome-positive chronic myelogenous leukemia. Oligomerization of Bcr-Abl is essential for oncogenicity. We determined the crystal structure of the N-terminal oligomerization domain of Bcr-Abl (residues 1-72 or Bcr1-72) and found a novel mode of oligomer formation. Two N shaped monomers dimerize by swapping N-terminal helices and by forming an antiparallel coiled coil between C-terminal helices. Two dimers then stack onto each other to form a tetramer. The Bcr1-72 structure provides a basis for the design of inhibitors of Bcr-Abl transforming activity by disrupting Bcr-Abl oligomerization. PMID- 11780147 TI - Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor. AB - Tonicity-responsive enhancer binding protein (TonEBP), also known as NFAT5, is a unique member of the NFAT family of transcription factors that regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of the NFAT family, TonEBP exists as a homodimer and binds asymmetric TonE DNA sites; furthermore, the affinity of TonEBP for DNA is much lower than that of other NFAT proteins. How TonEBP recognizes the TonE site and regulates the activation of hypertonicity response genes has not been clear. Here we show that TonEBP adopts a NF-kappaB-like structure upon binding to DNA, providing a direct structural link between the NFAT and NF-kappaB family of transcription factors. We also show that TonEBP completely encircles its DNA target and present biochemical evidence that the DNA encirclement may lead to increased kinetic stability of the TonEBP-DNA complex. Thus, the list of proteins that bind DNA by encirclement is now expanded to include sequence-specific transcription factors. PMID- 11780148 TI - [Medical-psychological consultation at San Roque hospital]. AB - This paper has been done to comunicate a conception of Interconsultation (Liaison) developed in the Metal Health Service from San Roque Hospital. It begins with a general review around theoretical and technical evolution about Interconsultation in a general Hospital. Then it describes our theoretical point of view and its instrumentation, with especial enphasis in the idea of "to include the human being of our sick subject". The article affirms the necessity of thransferencial relantionship among Interconsultator and Interconsultant. All process is representated by diagrams. In them, we can see the identification of problems, the strategies and tactics that determine courses of action, and how to evaluate these procedures. PMID- 11780149 TI - [The conception of negative in Henri Ey organodynamics]. AB - The concept of "negative" goes over the organodynamics of Henri Ey in its entirety. It is his fundamental concept. We owe him the epistemological unit of a theory that involves the body and the spirit, the biological aspects and the psychological ones, the chemotherapy and the psychotherapy. This unit has become valuable in our time of eclecticism multifactorial, always threatening of explosion or of division between neurosciences and psychotherapies with the consequences that one can imagine for our patients and for psychiatrist's profession. PMID- 11780150 TI - [Classification of memory systems: a revision]. AB - The present paper exposes the arguments against considering memory as a monolytic entity and how is it to be divided into several systems in order to understand its operation. Historically this division was acknowledge by different authors but in the last few decades it received the confirmation from the scientific research. The most accepted taxonomy establishes the existence of two major memory systems: declarative and non declarative memory. The article also presents the arguments for and against this kind of division, as well as an alternative classification in five major systems: procedural, perceptual representation, semantic, primary and episodic. PMID- 11780151 TI - [Importance of the neuropsychological assessment of memory in the clinical practice]. AB - Memory assessment is used to diagnose possible disturbances of this function and to relate the findings to their neurological implications and to the issues of clinical treatment and prognosis. Neuropsychological examination of memory function involves (a) the administration of objective procedures that are proven sensitive to the effects of brain injury, and specific to the changes due to functional impairment, and (b) the integration of statistical and observational findings that demonstrate a consistent pattern of results that are commonly seen with specific brain disorders. Analysis of the pattern of performance among the tests is key to a good understanding of the results; thus, the selection of tests used should sample a wide range of memory domains. This paper analyzes the most frequently measuring instruments in neuropsychological assessment of memory, as well as the main batteries and tests used to evaluate the existence or absence of mnesic deficits. PMID- 11780152 TI - [Drug associated memory impairment]. AB - There are lots of conditions producing memory impairment. It must be taken into account, not only degenerative diseases like Alzheimer Disease; but also epilepsy, depression, stress, recreational drug abuse, thyroid diseases, etc. In this article we'll comment on one of the more common and current ways of having memory disorders such as some medications currently in use, especially by old people. As physicians, we usually "forget" that many prescription medicines or over the counter remedies could have the potential hazard of producing severe memory impairment or delirium. In our country, benzodiazepines, are one of the most prescribed drugs used to deal with anxiety disorders, and are usually taken chronically almost without professional surveillance producing memory disorders as well as depression, addiction, etc. Other medications, like antidepressants, anticonvulsants, sedatives, cardiological drugs, nonsteroidal anti-inflammatory drugs will be also discussed. PMID- 11780153 TI - [Autobiographic memory. Neurobiological substrates]. AB - This work reviews the cellular mechanisms, and the cerebral areas and circuits participating in the consolidation of episodic memory. At the cerebral level the circuit which connects the primary sensory cortices with the polimodal cortices, the entorhinal cortex, dentate gyrus, hippocampus and associative cortices is sequentially activated when the consolidation of a mnesic trace takes place. Cellular phenomena associated with this process is the long-term potentiation (LTP) which requires the activation of NMDA and AMPA receptors, the uptake of calcium and the activation of several enzymes which on one hand catalize the synthesis of retrograde messengers as nitric oxide and on the other induce genomic changes with trophic consequences for both the post and the presynaptic neurons. Eventual relationships between neurobiological findings and mnesic phenomena observed in psychoanalytic practice should be further investigated. PMID- 11780154 TI - [Memory and cognitivism]. AB - The goal of this article is to explore the notion of cognitive memory. For that reason we would study the implicit and explicit memory. We would also study the notion of childhood amnesia and trauma. PMID- 11780155 TI - [Dementia: clinic and diagnosis]. AB - Decline of the cognitive functions necessary for activities of daily living results in a spectrum ranging from benign forgetfulness and minimal cognitive impairment to dementia. The latter is characterized by personality and behavioral changes. Alzheimer's disease is the most frequent cause of dementia affecting almost one of two people older than 80 years. Lewy body and cerebrovascular disease are also frequent causes of cognitive decline. Recent studies have revealed genetic aspects of Alzheimer's disease and the role of certain enzymes in the pathophysiology of fibrillary amyloid deposition. The aim in cognitive disease is an early diagnosis to initiate therapy and adapting measures in the patient's daily routines. The diagnosis is basically clinical with neuroimaging and neuropsychological tests' support. The EEG, SPECT, LP and other studies are only useful in a few specific scenarios. At present, a few promising therapies are being evaluated. Family support is of vital importance. PMID- 11780156 TI - [Some ideas to think the collective memory at the present time]. AB - This article raises some questions to understand the meaning of collective memory and the process of its social construction today. The relation between memory and identity is changing due to economic and cultural globalization. Notions like time and space, that define memory change their meaning and raise new social relations. PMID- 11780157 TI - [Memory]. PMID- 11780158 TI - [Dialectics of the imaginary in schizophrenia]. PMID- 11780159 TI - [Psycho-neuro-immuno-endocrinological psychiatry]. PMID- 11780160 TI - [Multi-family psychoeducational group in the prevention and treatment of eating disorders]. PMID- 11780161 TI - [Detection of psychopathological risk factors in the Medico-surgical emergency services of the San Roque Hospital]. PMID- 11780162 TI - [Ethics and dementia in medical practice]. PMID- 11780163 TI - [Analysis of the response to stress. Theoretical and methodological aspects]. PMID- 11780164 TI - [The interrelationship between thyroid gland, psychology and psychiatry]. PMID- 11780165 TI - [Personality, interpersonal schemes and social context in the evolution of diabetes in children and adolescents]. PMID- 11780166 TI - [Different cognitive styles in the perception of and dealing with dyspnea]. PMID- 11780167 TI - [The construction of the "meaning of the disease" for the patient. Its relation to the etiology and prognosis of the cardiovascular disease]. PMID- 11780168 TI - Incidence of awareness in total intravenous anaesthesia. PMID- 11780169 TI - Use of pre-emptive vasopressors for spinal anaesthesia-induced hypotension during Caesarean section. PMID- 11780170 TI - [Premedication before endoscopy]. PMID- 11780171 TI - Abstracts of the 13th World Congress of the International Society for Artificial Organs. Osaka, Japan, November 5-8, 2001. PMID- 11780172 TI - Responses to "A comparison of characteristics of Kevorkian euthanasia cases and physician-assisted suicides in Oregon". PMID- 11780173 TI - Effects of tamoxifen on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis. PMID- 11780174 TI - Effects of tamoxifen on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis. PMID- 11780175 TI - Neurosurgical intervention for Parkinson's disease: an update. AB - For patients with advanced Parkinson's disease who do not respond to levodopa anymore, neurosurgical intervention is the only option. Cell transplantation has not met expectations as yet. Deep brain stimulation is gaining ground and currently seems to be the most efficient, flexible, and safe procedure. PMID- 11780176 TI - Subarachnoid sufentanil for early postoperative pain management in orthopedic patients: more disadvantages than benefits? PMID- 11780177 TI - [Postexposure HIV-prophylaxis in the eyes]. PMID- 11780178 TI - [Hypercholesterolemia]. PMID- 11780179 TI - The Rorschach Inkblot Test: a debate. The Rorschach Test is scientifically questionable. PMID- 11780180 TI - Prediction by positron emission tomography scanning survival in non-small cell lung cancer. PMID- 11780181 TI - Poor, minority, and ill seniors do not use all prescribed medicine because of cost. PMID- 11780182 TI - Texas oncologist head of National Cancer Institute. PMID- 11780183 TI - Gene associated with sudden death identified. PMID- 11780184 TI - Endothelial protein C activation in meningococcal sepsis. PMID- 11780185 TI - Endothelial protein C activation in meningococcal sepsis. PMID- 11780186 TI - Medicare reform. PMID- 11780187 TI - Long-term mortality in patients with myocardial infarction: impact of early treatment with captopril for 4 weeks. AB - OBJECTIVE: In an earlier interim report of the Chinese Cardiac Study (CCS-1) trial, 15,000 patients up to 36 hours after the onset of suspected acute myocardial infarction (AMI) were randomized to receive either oral captopril or matching placebo for one month. Results showed that captopril was associated with a non-significant reduction in 4-week mortality (681 [9.1%] captopril-allocated vs 730 [9.7%] placebo-allocated deaths; 2P = 0.19), but the long-term effects remained uncertain. The present study reports on the long-term effect of early captopril treatment on mortality and other major events in AMI patients of the earlier CCS-1 trial. METHODS: Long-term follow-up was carried out in those hospitals which had recruited more than 20 cases in the CCS-1 trial. 8000 patients with MI were thus selected for long-term follow-up. Data on 6749 patients (84.4%) were available. RESULTS: Patient characteristics were comparable between the treatment group (n = 3391) and the placebo group (n = 3358). Average follow-up time was 23.4 +/- 16.9 months; average age was 63.6 +/- 10.6 years, and 76.2% were male. At the end of the follow-up time, cardiac function of NYHA III IV was 9.0% in the treatment group and 9.8% in the placebo group; the reinfarction rate was 5.6% vs. 6.0%; total cardiovascular events were 32.9% vs. 34.3%. Total mortality was 11.9% (n = 404) vs 13.8% (n = 463), with a 13.8% reduction in the captopril group (P = 0.03). Cardiovascular mortality was 10.0% vs. 11.8% (P = 0.01), death due to heart failure was 4.1% vs. 5.5% (P = 0.01). From the above results, it is estimated that early treatment with captopril can save 19 lives per 1000 patients treated; patients with systolic blood pressure (SBP) > or = 100 mm Hg at entry would have a long-term mortality 12.4% in the treatment group vs. 13.8% in the placebo group (P = 0.04) and patients with a heart rate (HR) > or = 60/minute at entry would have a long term mortality 12.0% in captopril groups vs. 14.5% in the placebo group (P = 0.01). CONCLUSION: Early treatment with captopril during AMI for 4 weeks can significantly reduce long term total mortality. PMID- 11780188 TI - Astragali and Angelica protect the kidney against ischemia and reperfusion injury and accelerate recovery. AB - OBJECTIVE: To investigate the role of Astragali and Angelica (A&A) of Chinese herbs in acute renal ischemia/reperfusion injury, and the related intracellular signal transduction mechanism. METHODS: Acute ischemic renal injury in rats was induced by clamping in renal pedicel for 45 minutes. Rats in therapy group were given a single dose (2 ml/day) of A&A for 3 days before clamping, and then continued for another 3 days. Forty-five minutes after clamping and at different reperfusion time, serum creatinine (Scr) and renal pathological changes were taken and compared in both groups. The proliferating cell nuclear antigen (PCNA) positive cells were detected by immunohistochemistry. Extracelluar regulating kinase (ERK) and c-Jun N-terminal kinase (JNK) activity was assayed by specific substrate phosphorylation with immunoprecipitation. RESULTS: At the 24th hour of reperfusion, Scr was lower in A&A group than that in the control. Much less necrotic tubular cells, casts, and more PCNA-positive cells were found in A&A group. ERK activity decreased after clamping, and recovered at 5 minutes of reperfusion. There was no difference between the two groups. JNK activity did not change after ischemia, but increased at 5 minutes and peaked at 20 minutes of reperfusion. JNK activity was significantly higher in A&A group than that in the control group. CONCLUSION: A&A protected kidney against ischemic insult and accelerated both functional and histological recovery after acute renal ischemia/reperfusion injury, which may associate with the change of JNK signaling pathway. PMID- 11780189 TI - Construction and primary characterization of Echinococcus multilocularis protoscolex cDNA expression library. AB - OBJECTIVE: To construct a lambda gt11 cDNA expression library of Echinococcus multilocularis protoscolex isolated in China. METHODS: Echinococcus multilocularis protoscolex mRNA was extracted using a Quickprep MicromRNA purification kit based on combining of the disruptive and protective properties of guanidinium thiocyanate (GTC) with the speed and selectivity of oligo (dT) cellulose chromatography in a spum-column with some modification. Purified mRNA (1.8 micrograms) was submitted to reverse transcription using random hexamers [pd(N6)]. The double-strand blunt-ended cDNAs were ligated with an EcoRI/Notl adaptor to form a cohesive EcoRI end. Subsequently the synthesized cDNA was inserted into vector lambda gt11 EcoRI arms. After being packaged in vitro, lambda gt11 was put to an infectious bacteria Echinococcus coli (E. coli) strain Y1090; the recombinants were screened by color selection. PCR amplification was performed to evaluate the size of insertion DNA fragments. RESULTS: The recombinant ratio was nearly 100% and approximately 1 x 10(6) clones could be derived from this lambda gt11 cDNA library. PCR results indicated that the insertion DNAs were about 1.48 kb. CONCLUSIONS: A lambda gt11 cDNA expression library consisting of a million recombinant clones has been constructed from Echinococcus multicularis protoscolex mRNA. Further studies on this library are deserved. PMID- 11780190 TI - The role of sexual related Y gene detection in the diagnosis of patients with gonadal dysgenesis. AB - OBJECTIVE: To clarify the role of sexual related Y (SRY) gene detection in the diagnosis of gonadal dysgenesis. METHODS: Sixteen cases of gonadal dysgenesis were included in this study: 5 with androgen insensitivity syndrome, 1 with 17 alpha-hydroxylase deficiency, 4 with true hermaphrodite, 2 with 45, X/46, XY gonadal dysgenesis, 1 with 45, X gonadal dysgenesis, 1 with XY pure gonadal dysgenesis, 1 with testicular regression, and 1 XY female who gave birth to a normal baby. SRY gene was detected by using polymerase chain reaction (PCR) in blood and gonad samples and by direct sequencing of the SRY motif. RESULTS: Among the 16 cases, 15 were blood SRY positive, among which 13 (86.7%) showed the presence of testicular tissue, and 2 showed ovaries without testicular tissue. One SRY negative case showed the presence of testicular tissue. In 3 cases, SRY detection in gonadal tissue correlated with pathological findings but not with blood karyotype. The correlation between peripheral blood SRY and the pathology of the gonads was 81.25% and the correlation between the presence of peripheral blood Y chromosome and pathology of the gonads was 68.75%. Sequencing of the SRY motif in an XY female who gave birth to a normal baby showed no mutation. CONCLUSIONS: SRY detection is more sensitive and specific than blood karyotype in the prediction of the presence of testicular tissue. Peripheral blood karyotype does not necessarily reflect gonadal type. There may be testicular related factors other than the SRY gene. PMID- 11780191 TI - Epstein-Barr virus infection of sinonasal lymphoepithelial carcinoma in Guangzhou. AB - OBJECTIVES: To investigate the prevalence of sinonasal lymphoepithelial carcinoma (SNLEC) in Guangzhou, a high incidence area of nasopharyngeal carcinoma (NPC), and to detect whether it is associated with Epstein-Barr virus (EBV) infection. METHODS: Twenty confirmed SNLEC specimens were collected from all of the sinonasal carcinoma biopsies performed in the 8 years 1989-1996 at the Sun Yat sen University of Medical Sciences. EBV encoded early RNAs were detected by use of in-situ hybridization. A variety of antigens, including the EBV nuclear antigen 1, latent membrane protein 1, BZLF1 protein, diffuse early antigen, viral capsid antigen and membrane antigen, were detected using immunohistochemistry. Additionally, 36 NPC specimens were used for comparison. RESULTS: Twenty SNLECs were identified. Seventeen SNLECs were developed in the nasal cavity, and 3 in the maxillary sinus. The mean age (46.25 y), male to female ratio (3:1), histopathology and lymphoinfiltration of the 20 SNLECs were identical with those of the 36 NPCs. Thirteen (65.0%) of the 20 SNLECs showed an expansive growth pattern, while 27 (75.0%) of the 36 NPCs showed an infiltrating or mixed growth pattern. The majority of cancer cells in all of the 20 SNLECs showed EBV encoded early RNAs. The EBV nuclear antigen 1 expression of SNLEC was less intensive than that of NPC. The expression rate of latent membrane protein 1 for SNLEC (3/20, 15%) was lower than that for NPC (19/36, 52.8%). The expression rates of BZLF1 protein (2/20, 10.0%), diffuse early antigen (19/20, 95.0%), viral capsid antigen (15/20, 75.0%), and membrane antigen (13/20, 65.0%) for SNLEC were higher than those (0/36, 0.0%; 31/36, 86.0%; 18/36, 50%; and 14/36, 38.9%) for NPC. CONCLUSIONS: SNLEC is not uncommon in Guangzhou. This tumour is also consistently associated with EBV infection like NPC. As compared to NPC, the EBV harbored in SNLECs seems to express the EBV nuclear antigen 1 weakly and has a lower expression rate of latent membrane protein 1 as well as higher expression rates of EBV lytic products. PMID- 11780192 TI - Analysis of 20 mature ovarian cystic teratoma cases in postmenopausal women. AB - OBJECTIVE: To study the incidence of malignant change, diagnosis and management of mature cystic teratomas in postmenopausal women. METHODS: Twenty cases of mature cystic teratoma in postmenopausal women admitted to our hospital between January 1977 and January 1997 was retrospectively reviewed and evaluated. RESULTS: The number of postmenopausal patients with mature cystic teratoma (20) accounted for 7.6% of the total number of patients with benign ovarian teratomas (263). There were 3 cases of malignant change, which were squamous carcinoma, carcinosarcoma, and digestive gland epithelial carcinoma. The incidence of malignant change was 15%. CONCLUSION: In postmenopausal women, mature ovarian cystic teratoma should be treated as lowly malignant and should be paid much attention. PMID- 11780193 TI - Interferon-gamma inhibits in situ expression of PDGF-beta mRNA by smooth muscle cells in injured rabbit arteries after transluminal balloon angioplasty. AB - OBJECTIVE: To elucidate the mechanism of interferon-gamma (IFN-gamma) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA). METHODS: A rabbit vascular restenotic model was constructed and the proliferation of intimal smooth muscle cells (SMCs) were observed by monitoring their expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor beta chain mRNA (PDGF-beta mRNA) at the indicated time points. RESULTS: IFN-gamma could significantly inhibit the expression of PCNA by intimal SMCs one week after denudation, when counting 200 intimal cells for PCNA-positive reactions with an inhibitory rate of 88.50% (P < 0.001). IFN-gamma could downregulate in situ expression of PDGF-beta mRNA by these cells as we calculated the average number of PDGF-beta mRNA positive cells per square millimetre area at x 400 magnification with reduced rates of 86.85% in 1 week group (P < 0.001), of 93.66% in 2 week group (P < 0.001) and of 52.92% in 4 week group (0.02 < P < 0.05), respectively. CONCLUSIONS: The local production of PDGF-beta by vascular intimal SMCs via an autocrine mechanism may be responsible for continuous proliferation of these cells and the formation of neointima after injury. This could be inhibited by IFN-gamma through downregulating the expression of PDGF beta mRNA. These results provide an in vivo basis for IFN-gamma to be used clinically for the management of restenosis after percutaneous transluminal angioplasty. PMID- 11780194 TI - Modified cold storage of rat livers with self-made HYD solution. AB - OBJECTIVE: To investigate the cold preservation effect on rat livers of a modified storage method with self-made HYD solution. METHODS: The vascular bed of rat livers was expanded with an additional 20 to 40 ml self-made HYD solution/100 g liver. After resection of the liver, the extra HYD solution (expressed as % liver weight) was entrapped via portal infusion by tying off the supra- and infra hepatic inferior vena cava. Forty rats were randomly divided into four groups including control group with conventional storage method, and 20%, 30% and 40% groups according to the amount of extra HYD solution. We compared the preservation effect of the modified storage method with that of the conventional storage method using an isolated perfused rat liver model. RESULTS: Bile production and all the indices of hepatic microcirculation including portal perfusion pressure, endothelin-1 in the effluent, trypan blue distribution time and histology were significantly superior in the modified method groups compared to those in the control group (P < 0.05). The contents of dihydroxybenzoic acid (DHBA) in the modified method groups were significantly lower than those in the control group (P < 0.05). Liver enzymes activities in the 30% group were markedly lower than those in the control group (P < 0.05). The preservation effect on rat liver in the 30% group was the best among the modified method groups. CONCLUSION: The modified cold storage method is effective and may have potential for clinical application in liver preservation. PMID- 11780195 TI - Characteristics of ovarian cancer cells transduced by the bicistronic retroviral vector containing GM-CSF and HSV-TK genes. AB - OBJECTIVES: To explore whether HSV-TK (herpes simplex virus thymidine kinase) and GM-CSF (granulocyte-macrophage colony-stimulating factor) genes could be linked by internal ribosome entry site (IRES) in one retroviral vector and expressed by ovarian cancer cells following transfection, and to observe the characteristics of the transduced cells. METHODS: Retroviral vector pLGM-I-TK was constructed by linking the HSV-TK gene and GM-CSF gene with the IRES sequence. By using the "ping-pong" technique, pLGM-I-TK was transfected into the packaging cell line, PA317, to produce a PA317/TK-GM cell line. Using the resulting viral supernatant to infect the ovarian cancer cell line SKOV3, PCR and RT-PCR were used to explore the integration and transcription of HSV-TK and GM-CSF genes. The cytotoxicity of GCV (gancyclovir) on SKOV3/TK-GM was determined by MTT assay and the bystander effect of the HSV-TK/GCV system was also assessed. ELISA was used to measure the expression of GM-CSF by the transgene cells. RESULTS: The bicistronic retroviral vector constructed could be successfully transduced into PA317 and the titer of the retroviral vector was about 8.6 x 10(5) cfu/ml. PCR and RT-PCR demonstrated the successful integration and transcription of HSV-TK and GM-CSF genes transduced into the SKOV3 cell. SKOV3/TK-GM cells could be killed by GCV, and the IC50 was 0.7 microgram/ml. The bystander effect was demonstrated. The expression level of GM-CSF in SKOV3/TK-GM was 60.4 ng.ml-1 x 10(6) cells-1 x 2 days-1. CONCLUSION: The IRES sequence can be used to construct retroviral vectors to facilitate co-transfection of two genes. SKOV3/TK-GM cells can simultaneously express the HSV-TK and GM-CSF genes with biological activities which could be useful for enhancing the function of immune cells on the basis of suicide gene therapy. PMID- 11780196 TI - Expression of beta-catenin in renal cell carcinoma. AB - OBJECTIVE: To investigate the expression of beta-catenin and its mRNA in renal cell carcinoma. METHODS: Twenty-six cases with renal cell carcinoma (RCC) were studied by immunohistochemistry, Western blot and RT-PCR. RESULTS: We found the expression of beta-catenis is higher in cancer tissues than in normal kidney tissues and the level of beta-catenin is associated with the tumor stage. Its expression in tumor of pT3 and pT4 is obviously higher than pT1 and pT2 (P < 0.01). That is to say, there was an overexpression of beta-catenin protein in RCC and its level was related to the tumor stage, but the expression of beta-catenin mRNA had no difference between tumor tissue and normal tissue. CONCLUSION: beta catenin may be related to the occurrence and progress of RCC. PMID- 11780197 TI - Recording of spared motor evoked potentials and its augmentation by 4 aminopyridine in chronic spinal cord-injured rats. AB - OBJECTIVE: To research the direct electrophysiological evidence of discomplete spinal cord injury (SCI) and the effect of 4-aminopyridine on it. METHODS: Motor evoked potentials (MEPs), both spinal cord recorded MEPs (scMEPs) and extracellularly recorded MEPs (exMEPs) were recorded and characterized on a T13 epidural electrode (scMEPs) and an extracellular microelectrode (exMEPs) for 10 normal rats and 40 rats with lesions of various severity (sham, 35 g.cm force (gcf), 70 gcf, 100 gcf impact injury) at the T8-T9 cord using the Allen's drop model. The incline plane and Tarlov techniques were used to assess clinical neurological function. RESULTS: MEPs in the normal rats were elicited by applying transcortical suprathreshold stimulation consisting of 3-4 early negative peaks (N1, N2, N3 and N4) followed by several late waves. The N1 and N2 peaks were largest in the anterior and ventrolateral funiculus, respectively, which was indicative of extrapyramidal pathways. The 100 gcf impact injuries and the cord transection abolished the MEP distal to the lesion, whereas the 35 gcf injuries resulted in a latency shift and amplitude decrement of the MEP peaks. Eighteen of the 20 rats with 70 gcf-injuries showed clinical paraplegia. Among them, 7 rats had neurophysiological evidence of residual conduction pathways through the lesioned cord segment, such as the presence of N1 and N2 peaks in the scMEPs or exMEPs. After 4-aminopyridine (4-AP) administrations (1 mg/kg), the amplitude of the spared exMEP increased significantly and spread more widely. CONCLUSIONS: MEPs evoked by transcortical stimulation travel mostly in the extrapyramidal tract. MEP monitoring could provide an excellent method of detecting the functional integrity of the motor tracts after SCI, and could even detect spared motor fibers after discomplete SCI. Furthermore, the use of 4-AP or other K+ channel blocking agents may be a potential treatment for patients with chronic moderate to severe SCI. PMID- 11780198 TI - Anti-Fas antibody induces apoptosis in cultured human renal interstitial fibroblasts. AB - OBJECTIVE: To detect if Fas is expressed in human renal interstitial fibroblasts (hRIFs) and apoptosis of hRIFs can be induced by specific anti-Fas antibody. METHODS: hRIFs were cultured from isolated papillae of human kidney, and identified by morphologic examination, assay of antigenic components and culture in D-valine selective medium. Fas expression in normal hRIFs was detected by RT PCR and immunocytochemistry staining. After hRIFs were incubated with interferon gamma (gamma-IFN 500 U/ml, 1000 U/ml, 1500 U/ml and 2000 U/ml, respectively) for 48 hours, Fas expression was determined by Northern blot, Western blot and flow cytometry. hRIFs pre-stimulated with gamma-IFN (500 U/ml, 48 hours) were incubated with anti-Fas antibody (IgM, 0.5 microgram/ml) for 12 hours. And apoptosis was identified by morphologic examination, DNA ladder assay and flow cytometry. RESULTS: The cultured hRIFs showed a shuttle-like shape and were positively stained by labeled anti-vimentin antibody but negatively stained by anti-epithelial membrane antibody. They could not grow in the D-valine selective medium and died partly in a week. Fas mRNA and protein were expressed in normal hRIFs and markedly upregulated by stimulation with gamma-IFN. Apoptosis in gamma IFN pre-stimulated hRIFs was induced by anti-Fas antibody, showing cell nuclear shrinkage and condensation in morphologic feature, internucleosomal DNA fragmentation in DNA ladder assay and a pick of hypo-diploid nuclei by flow cytometry. CONCLUSION: Fas is normally expressed in hRIFs and can be markedly upregulated by gamma-IFN. Anti-Fas antibodies can induce apoptosis of hRIFs pre stimulated with gamma-IFN. PMID- 11780199 TI - Post-PRK muscular asthenopia and eccentric ablation. AB - OBJECTIVE: To investigate the relationship between muscular asthenopia post photorefractive keratectomy (PRK) and eccentric ablation. METHODS: 16 eyes of 8 myopia cases whose muscular asthenopia was corrected by subjectively accepted triangular prism after PRK with vision more than 0.8 were followed up for 6-14 months. On the basis of data provided by the pre-PRK, post-PRK and their difference corneal topography, we calculated the real corrected corneal diopter (D) with the Holladay formula and measured the ablating eccentricity (h) and its direction. According to the formula delta approximately Dh, the prism effective value (delta) caused by the eccentric ablation was computed and compared with objectively accepted triangular prism. RESULTS: The subjectively accepted prism was similar to values calculated from the formula. Their mean difference is 0.10 +/- 0.25. The direction of the subjectively accepted prism was in the direction of ablation deviation. CONCLUSIONS: Eccentric ablation was the chief cause of post-PRK muscular visual asthenopia. The triangular prism effective value from eccentric ablation may be estimated by the formula delta approximately Dh. We must pay attention to the diagnosis, treatment and prevention of post-PRK muscular asthenopia. PMID- 11780200 TI - Retinoic acid regulated insulin-like growth factor gene expression in cord blood lymphocytes. AB - OBJECTIVE: To explore the immune promotion mechanism of retinoic acid (RA). METHODS: Reverse Transcription-Polymerase chain reaction (RT-PCR) was used to detect the gene expression of insulin like growth factor I (IGF-I) and IGF receptors (IGF-IR and IGF-IIR) in vitro, and their regulation by RA in human cord blood lymphocyte (CBL). RESULTS: Significant upregulation of IGF-I, IGF-IR and IGF-IIR mRNA was found at 6-24 hours in CBL incubated with physiologic concentrations of RA as compared to those without RA. CONCLUSION: The enhancement of IGF expression may be an important pathway for vitamin A to promote immune cellular functions. PMID- 11780201 TI - How to use progestin in hormone replacement therapy: an animal experiment. AB - OBJECTIVE: To determine whether continuous or cyclic hormone replacement therapy (estrogen and progestogen) is better. METHODS: One hundred and forty Sprague Dawley rats were randomly divided into seven groups. The 1st and 2nd groups were normal estrous and ovariectomy (OVX) controls. Treatment of the other groups imitated the clinical regimen (continuous and cyclic) with estradiol valerate (E2V) and medroxy progesterone (MPA) in different ratios of combination. The rats were sacrificed and sections of uterus were stained with HE and histochemical methods to detect mitosis and proliferating cell nuclear antigen (PCNA), respectively. The mitotic index (MI) and PCNA index were calculated. RESULTS: The MI and PCNA index were similar in luminal and glandular cells. Both markers were low in the two control groups. When E2V was given for 1 to 6 days, both the MI and PCNA index increased with duration of treatment. When MPA was added, both markers were reduced to a very low level. In the continuous regimen, both markers decreased as the MPA dosage increased. The ratio of E2V: MPA = 1:0.5 was enough to suppress markers to a low level similar to that of normal estrous rats. A further increase in the ratio to 1:1.0 showed no further decrease in PCNA index. In the cyclic regimen, MPA was added for the last 5 days. The mitotic index reached a significantly low level near 0 in all ratios, but the PCNA index in each subgroup was still as high as the positive control, even though the dosage of MPA was increased several times to 1:8.0. When MPA was added for the last 10 days, the PCNA index at a ratio of 1:4.0 could be reduced to a low level. CONCLUSION: The results of this study suggest that the continuous regimen was better than the cyclic regimen in postmenopausal hormone replacement therapy (HRT). Progestin should be given for at least 10 days in the cyclic regimen. PMID- 11780202 TI - ATP sensitive K+ channel may be involved in the protective effects of preconditioning in isolated guinea pig cardiomyocytes. AB - OBJECTIVE: To develop a cellular model of preconditioning by a brief period of hypoxia in isolated guinea pig cardiomyocytes and to determine whether or not an ATP sensitive K+ (KATP) channel is involved in ischemic preconditioning. METHODS: Single myocytes were isolated from the ventricle of adult guinea pigs. The experimental chamber allowed the cells to be exposed to low O2 pressure. During hypoxic preconditioning, the cells were equilibrated with normaxic solution for 10 minutes and then exposed to hypoxia for 5 minutes, followed by 10 minutes of reoxygenation. The cells were then subjected to 20-180 minutes of hypoxia and reoxygenation. Ionic currents were studied with the patch clamp technique in whole-cell and cell-attached configurations. RESULTS: A 5-minute hypoxic preconditioning offered a significant protection from cell injury in subsequent hypoxia-reoxygenation. After a latency of more than 15 minutes, hypoxia induced a time-independent outward K+ current which could be blocked by 5 mumol/L glibenclamide. At 10 mV, the current increased from 78 +/- 15 pA to 1581 +/- 153 pA (P < 0.01, n = 18). However, the latency to develop KATP channel currents (IKATP) was greatly shortened in preconditioned cells, and the current was increased acceleratively. At 10 mV, the current more than 4 nA was recorded in preconditioning cells. In the single channel recordings, the time interval from the first channel opening to maximum opening was also markedly abbreviated in preconditioned cells. CONCLUSION: Isolated guinea pig cardiomyocytes can be preconditioned with a brief period of hypoxia. This hypoxic preconditioning may modify the KATP channel, and make the channel open more readily during the second hypoxia. PMID- 11780203 TI - Alterations in myosin heavy chain isoform gene expression during the transition from compensatory hypertrophy to congestive heart failure in rats. AB - OBJECTIVE: To explore the molecular mechanism underlying the decreased velocity of tension rise in rat myocardium during congestive heart failure (CHF) and left ventricular hypertrophy (LVH) induced by aortic stenosis. METHODS: The maximum velocity of tension rise (+dT/dtmax) was measured in left ventricular papillary muscle and the mRNA level of myosin heavy chain (MHC) isoforms in the left ventricle were detected by Northern blot analysis. RESULTS: The value of +dT/dtmax in CHF and LVH group were 64.17% and 37.15% lower than sham-operated controls (Sham) (P < 0.01); values in the CHF group were 42.99% lower than that of LVH (P < 0.01). The level of alpha-MHC mRNA in LVH was not different from that of the Sham (P > 0.05), but decreased significantly in CHF to 42.3% of Sham and 56.1% of LVH (P < 0.01). The level of beta-MHC mRNA was up-regulated by 88.3% (P < 0.01) in LVH compared with Sham and the level of beta-MHC in CHF was 1.5-fold and 3.7-fold higher than that in LVH and Sham respectively (P < 0.01). The ratio of alpha-MHC/beta-MHC mRNA in LVH and CHF decreased to 42.4% and 9.8% respectively of the value in Sham (P < 0.01). Correlation between alpha-MHC/beta MHC mRNA level and +dT/dtmax was analyzed which showed that these values were positively correlated with a correlation coefficient of 0.875 (P < 0.01). CONCLUSION: The decreased ratio of alpha-MHC/beta-MHC mRNA was the major molecular mechanism underlying the decreased +dT/dtmax in CHF and LVH myocardium. The decreased ratio of alpha-MHC/beta-MHC mRNA in LVH was mainly due to the up regulation of beta-MHC mRNA while in CHF both down regulation of alpha-MHC and up regulation of beta-MHC were involved. PMID- 11780204 TI - In vitro renaturation of recombinant human pro-urokinase expressed in Escherichia coli. AB - OBJECTIVE: Recombinant human pro-urokinase forms insoluble inclusion body when overexpressed in Escherichia coli. It must be denatured and renatured in vitro so that it can acquire activity. This study aimed at increasing the renaturation yield of denaturant pro-urokinase. METHODS: We evaluated the basic renaturation conditions of pro-urokinase through qualitative and quantitative analysis of pH, temperature, denatured concentration, protein concentration, and the ratio of reduced and oxidized thiol reagents. We also compared the effects of nonspecific additives, step-wise dilution and urea gradient dialysis. RESULTS: We defined the optimal conditions of pro-urokinase renaturation with a yield of about 20%-30%. CONCLUSION: Different recombinant denatured proteins have different renaturation conditions due to their different molecular sizes, molecular constructions, disulfide bond numbers, and hydrophobicity. The renaturation yield can be increased by optimizing the renaturation conditions of a specific protein. PMID- 11780205 TI - Low incidence of severe aGVHD and accelerating hemopoietic reconstitution in allo BMT using lenograstim stimulated BM cells. AB - OBJECTIVES: To investigate the efficacy of accelerating hemopoietic reconstraction and reducing a graft versus host disease (GVHD) in Allo-BMT receiving lenograstim stimulated donor marrow and to assess the preliminary biological mechanism. METHODS: The donors for thirty patients (study group) with leukemia were given lenograstim 3-4 micrograms.kg-1.d-1 for seven days prior to marrow harvest. The results of subsequent engraftment in the recipients was compared with fifteen donors without G-CSF (control group). Five donors themselves were studied to assess the effects of lenograstion on hematopoietic progenitor cells and lymphocyte subsets in BM. RESULTS: The stimulated bone marrow contained a higher number of nucleated cells, CFU-GM and CD34+ cells (P < 0.01). The hematopoetic reconstitution was accelerated. Until granulocyte counts exceeded 0.5 x 10(9)/L and plalete counts exceeded 20 x 10(9)/L, the days were 16.7 +/- 3.2 and 18.4 +/- 3.0 days as compared with those of the control group (22.5 +/- 5.1 and 26.3 +/- 5.9 days respectively, P < 0.01). The incidence of grade II-IV aGVHD was very low, only one case with grade II aGVHD on the skin in the study group. Four out of fifteen patients (26.7%) in the control group had grade II-IV aGVHD (P < 0.05). The number of T lymphocyte subsets in the harvested BM stimulated by G-CSF changed. In comparison with the control group, CD4+ decreased and CD8+ increased significantly (P < 0.01). The changes of progenitor cells and T lymphocyte subsets in BM from pre- to post-G-CSF stimulation indicated that the percentage of CD4+ cells reduced (P < 0.05), that of CD8+ cells, and that of CD34+ increased (P < 0.01). The incidence of chronic GVHD and relapse of leukemia were not different significantly between both groups. CONCLUSIONS: Allogenic bone marrow transplant (Allo-BMT) donors given G-CSF can accelerate engraftment and minimize the incidence of severe aGVHD. There is a trend in favour of improved transplant-related complications. PMID- 11780206 TI - Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors. AB - OBJECTIVE: To evaluate the long-term therapeutic effects of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the treatment of hematological and solid tumors. METHODS: Fifty-one patients were recruited in this auto-PBSCT study, in which several potentially important parameters were studied including the optimal time for stem cell collection, the dose of stem cell reinfusion, the time of hematopoietic reconstitution, the disease free survival (DFS) and overall survival (OS), complications related to transplantation, and maintenance chemotherapy after auto-PBSCT. RESULTS: After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AML were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% respectively. Hematopoietic reconstitution was greatly promoted by granulocyte colony stimulating factor (G-CSF). The mean time for patients' neutrophil to recover up to > 0.5 x 10(9)/L after APBSCT was 11.14 days in the group of the patients receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications. CONCLUSION: Comparing with conventional chemotherapy, our study suggests that auto-PBSCT is a very important therapeutic option that can significantly improve the prognosis in the patients with hematological and solid tumors, especially in the patients with AML and NHL. PMID- 11780207 TI - Cytogenetic analysis in 61 couples with spontaneous abortions. AB - OBJECTIVE: To examine the relationship between spontaneous abortion and chromosomal abnormalities. METHODS: Couples who had one or more consecutive spontaneous abortions and had normal genitals were enrolled for cytogenetic karyotype analysis. RESULTS: In the 61 couples, the detected incidence was 11.5%, with five Robertsonian translocations, one reciprocal translocation, and one pericentric inversion of chromosome 7. CONCLUSION: Chromosomal abnormalities may play an important role in fetal wastage. PMID- 11780208 TI - Primary omental torsion in a 12-year-old boy. PMID- 11780209 TI - Pulmonary hypertension with a huge thrombosis in main stem of pulmonary artery. PMID- 11780210 TI - A case of pyrexia, hepatosplenomegaly, cytopenia and hypergammaglobulinemia. PMID- 11780211 TI - Risk of stroke after acute myocardial infarction among Chinese. PMID- 11780212 TI - Factors affecting the pathogenesis of ankylosing spondylitis. PMID- 11780214 TI - [Advance of orthognathic surgery in China]. PMID- 11780215 TI - [Intraoral distraction osteogenesis]. AB - OBJECTIVE: To study the application of intraoral distraction osteogenesis in correction of various dentofacial deformities. METHODS: From 1997, 12 cases with various dentofacial deformities were corrected by using 6 kind of intraoral distractor. 3 cases of them were the patients with cleft palate who have severe secondary maxillary hypoplasia. 4 cases with hemifacial microsomia, 2 cases with micrognathia and 3 cases with partial mandibular defect. The maxillae were elongated from 10 mm to 15 mm, the mandibles were elongated from 15 mm to 25 mm, the vertical mandibular distraction was from 10-15 mm. RESULTS: All cases were corrected satisfactorily and have no any complications. In 1 case the distractor did not work during distraction and was replaced. Another case the mandibular margin fractured after distraction, the rigid fixation was performed for it. CONCLUSIONS: The intraoral distraction osteogenesis provides a new method with many advantages for those dentofacial deformities that are difficult correct by using ordinary orthognathic surgery. PMID- 11780213 TI - Clinical effects and bronchoalveolar transfer of levofloxacin in patients with community-acquired pneumonia. PMID- 11780216 TI - [Correction of dento-maxillofacial deformities by using both of orthodontics and orthognathic surgery]. AB - OBJECTIVE: To study the clinical results and stability after correction of dento maxillofacial deformities by using both of orthodontics and orthognathic surgery. METHODS: A group of 45 patients with dento-maxillofacial deformities were corrected by preoperative orthodontics-orthognathic surgery-postoperative orthodontics procedure. As a control, another group of 64 patients with the deformities were corrected by orthognathic surgery only. The facial appearance, occlusion and stability of two groups after correction were investigated and compared. RESULTS: In orthodontics and orthognathic surgery group, 62.2% of patients declared that their mastication were improved. Relapse rate of deformities was 4.4%. In orthognathic surgery group, 42.2% of patients declared that their mastication were improved. Relapse rate of deformities was 9.4%. CONCLUSIONS: Using both of orthodontics and orthognathic surgery to correct dento maxillofacial deformities is a good approach to improve results of correction, keep balance of occlusion and reduce the relapse of the deformities. PMID- 11780217 TI - [Distraction osteogenesis for correction of maxillary constriction]. AB - OBJECTIVE: To study the methods and effects of distraction osteogenesis for correction of maxillary constriction. METHODS: 10 cases (5 males, and 5 females, aged 16-33 years, average 19.6) were treated by distraction osteogenesis for correction of maxillary constriction. Le Fort I osteotomy and palatal suture osteotomy for the upper jaw were made before opening of the Hyrax screw expander. Totally four times of opening the screw a day were performed. 2 cases were expanded unilaterally. The AP head films were analyzed using Image and Database Analysis System (IDAS) before and after expansion. RESULTS: 1. Expansion of upper arch was achieved done within a few days, and the maxilla, maxillary dental base and the posterior teeth were expanded as much as 3.84 mm, 3.25 mm, and 5.61 mm respectively. 2. The new bone was formed between the opened suture in two weeks, and filled the suture in 2 to 3 months. 3. Maxillary teeth tipped bucally a little bit. CONCLUSIONS: Distraction osteogenesis rapid maxillary expansion could get a good result following Le Fort I and palatal suture osteotomy for correction of maxillary constriction. PMID- 11780219 TI - [Correcting unfavourable intermaxillary relationship in partial edentulous area and simultaneous implant]. AB - OBJECTIVE: This study was to evaluate the result of correcting the unfavourable intermaxillary relationship with orthognathic surgery in the partial edentulous area and simultaneous implant. METHODS: 9 cases with jaw discrepency underwent orthognathic surgery for correcting the intermaxillary relationship and simultaneous implant surgery. The orthognathic operations were Le Fort I osteotomy with mandibular SSRO in 3 cases; simple mandibular SSRO in one case, subapical osteotomy of mandibular front area in 4 case; posterior maxillary osteotomy in one case, 25 implants were simultaneously placed in the edentulos and partial edentulos area. RESULTS: Result showed all 9 cases got the normal intermaxillary relationship post-operation, and implant prosthesis 8 months later, 3 cases with implant supported partial denture, one case with implant supported overdenture, 5 cases with ceramic crowns. Follow-up means 11 months, no implant lost. CONCLUSIONS: Base on this work, the authors believe combining orthognathic surgery and implant surgery is a feasible and reliable method in correcting unfavourable intermaxillary relationship in the implant related area for indicated patients. PMID- 11780220 TI - [Titer and avidity of serum antibody to Porphyromonas gingivalis before and after periodontal therapy]. AB - OBJECTIVE: To observe the changes of titer and avidity of serum antibody to Porphyromonas gingivalis (Pg) before and one month after periodontal therapy, and to observe the correlation of titer and avidity of anti-Pg IgG with clinical indices. METHODS: ELISA and DEA-ELISA were used to determine the titer and avidity of serum IgG antibody to Pg381 before and one month after periodontal treatment in 17 periodontitis patients and 6 healthy control subjects. RESULTS: The titers of anti-Pg IgG antibody were higher in periodontitis patients than in healthy control subjects (P < 0.001). All patients were seropositive (titers to Pg were higher than 2-fold above the median for control subjects). IgG antibody avidity to Pg in periodontitis patients were not found to be significantly lower than that in control group. The titers to Pg decreased significantly at one month after periodontal therapy, but antibody avidity didn't change. Serum anti-Pg antibody titers had a tendency of negative correlation with probing depth. The antibody titers were significant higher in periodontitis patients with < or = 5 mm mean probing depth than in patients with > 5 mm mean probing depth. CONCLUSIONS: It is suggested that the humoral immune response to Pg381 is protective and this protective effect mainly depends on the titer of antibody. PMID- 11780218 TI - [Comparison of effect of the mandible setbacked by SSRO and IVRO on gnathostomatic system]. AB - OBJECTIVE: To compare the effect of the mandible setbacked by sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) on gnathostomatic system. METHODS: 27 cases with mandibular prognathism were treated, 16 received SSRO and 11 IVRO. Their occlusal force and masticatory efficiency were measured preoperatively and at 3 and 6 months after operation. The condylar positions were assessed by radiography before surgery and at 6 months postoperatively. RESULTS: In three months postoperatively, the occlusal force and masticatory efficiency of IVRO group was decreased more than that of SSRO group. At six months postoperatively, the occlusal force and masticatory efficiency of SSRO group recovered quicker than IVRO group and better than that of before operation. In IVRO group, the occlusal force approached the preoperative level, the masticatory efficiency was better than preoperative value. 26/32 (81.2%) condyles were relatively retropositioned in SSRO group, 14/22 (63.6%) condyles were relatively forward positioned in IVRO group. CONCLUSIONS: The function recovery time after surgery was shorter in SSRO group. The masticator muscles were detached in varying degree and the bone segments healed slowly, the effect on gnathostomatic system was greater and recovery time after surgery was longer in the IVRO group. PMID- 11780221 TI - [Expression of S-100 proteins and intermediate filament proteins in pleomorphic adenoma]. AB - OBJECTIVE: To observe immunohistochemical expression of S-100A1, S-100A2, S 100A4, S-100A6, S-100B, K8.12, KL1, Vimentin, GFAP and NSE in pleomorphic adenoma of salivary gland, and to evaluate the differential localization of S-100 proteins and biological behaviour of neoplastic myoepithelial cells. METHODS: 23 cases of normal salivary gland and 60 cases of pleomorphic adenoma were embedded, in paraffin and were routinely diagnosed on the basis of hematoxylin and eosin stained sections. Serial sections at 4 microns from the paraffin embedded blocks were used for the immunohistochemical studies. RESULTS: Normal salivary glands had positive immunoreactivity for S-100A families, K8.12 and KL1 in the ductal cells, while S100B, GFAP and NSE were observed in peripheral nerve fibers innervating the gland. In pleomorphic adenomas, luminal tumor cells in duct-like structures had positive immunoreactivity for S-100A subfamilies and keratin. Nonluminal tumor cells had positive immunoreactivity for S-100B, as well as Vimentin, keratins detected by monoclonal K8.12 and KL1, GFAP and NSE. CONCLUSIONS: These findings may suggest that the neoplastic myoepithelial cells contain Ca2+ binding proteins which may have a role in the regulation of calcium ions or calcium signaling mechanisms in the modulation of extracellular matrix deposition in pleomorphic adenoma which may in turn affect the extracellular matrix synthesis as well as histomorphology of the tumor. PMID- 11780222 TI - [Classification of secondary nasal deformities associated with unilateral cleft lip]. AB - OBJECTIVE: To classify secondary deformities of cleft lip noses. METHODS: 56 patients with secondary nasal deformities of cleft lip were chosen at random. Cartilages of those noses were dissected and measured when correcting nasal deformity in order to find the relationship between anatomical anomaly of nasal cartilages and nasal deformity. RESULTS: Three grades of anatomical anomalies of the nasal framework were found. Grade I, the morphological anomaly occurs at lower third of the diseased side only. Grade II, the lower third of the another side is involved in addition. Grade III, the dorsum nasi is also deviated. CONCLUSIONS: This classification may be employed as a practical guide for surgical planning. PMID- 11780223 TI - [Effects of hexamethylene bisacetamide on in vitro adhesion, motility and invasion of human mucoepidermoid carcinoma cell line MEC-1]. AB - OBJECTIVE: To investigate the effects of hexamethylene bisacetamide (HMBA) on the in vitro adhesion, motility and invasion of human mucoepidermoid carcinoma cell line MEC-1. METHODS: MEC-1 cells were induced with 2 mmol/L of HMBA in vitro, the adhesion of MEC-1 cells to the reconstituted basement membrane Matrigel was investigated with MTT colorimetric assay; the motility and invasion of MEC-1 cells were assayed using biopore membrane Millicell-PCF inserts culture system. RESULTS: The adhesion of MEC-1 cells treated with HMBA for 30 min or 90 min reduced by 26.47% and 31.13%, respectively; the motility and invasion of MEC-1 cells treated with HMBA reduced by 63.49% and 67.65%, respectively. CONCLUSIONS: HMBA has anti-invasion effects on human mucoepidermoid carcinoma cells in vitro. PMID- 11780224 TI - [Periodontal regeneration by application of the porous beta-TCP/BMP artificial bone to Class II furcation defects]. AB - OBJECTIVE: To study the regeneration of periodontal tissue after the application of beta-TCP/BMP artificial bone to class II furcation defects. METHODS: Periodontal defects were produced surgically around premolar teeth in 4 dogs. The flap surgery was performed and the root surfaces were curetted to remove the periodontal ligament and the cementum. A synthetic bioabsorble barrier manufactured from poly DL-lactide was used. The defects were divided into 3 groups (beta-TCP/BMP + PDLLA, PDLLA, control). 12 weeks after surgery, the animals were sacrificed and the teeth with their supporting periodontium were processed for light microscopic evaluation. RESULTS: The definitive evidences of regeneration were founded both in BMP/GTR group and GTR group, but the BMP/GTR group exhibited more new bone formation, cementum deposition occupying the majority of the furcation defects than the other two groups. CONCLUSION: It was concluded that the beta-TCP/BMP artificial bone can be used in GTR technique to promote periodontal regeneration. PMID- 11780225 TI - [Study on composition of plaque fluid in individuals with no oral hygiene]. AB - OBJECTIVE: To study the change of composition in long-term plaque fluid after sucrose rinse and the cariogenicity of plaque. METHODS: 43 subjects, who had no regular oral hygiene and no tooth brushing at least for one year, were selected. According to their caries status, 27 as caries-free group and 16 as caries positive group. Plaque were obtained before and at 7 minutes after a 10% sucrose rinse. Additionally, plaque samples of 15 and 30 minutes after sucrose rinse from 11 subjects were collected. The pH value and the concentrations of organic acids and inorganic ions in plaque fluid were measured. RESULTS: At 7 minutes after sucrose rinse, pH and the concentration of ammonium were significantly decreased, and the concentrations of lactic acid and formic acid were significantly increased. All these changes were similar to those of short-term plaque. No significant difference with any single component of plaque fluid was found between caries-free group and caries-positive group, neither before sucrose rinse nor after sucrose rinse. CONCLUSIONS: Changes of the composition in the plaque fluid were basically similar between long-term and short-term plaque, but single component in plaque fluid could not reflect the cariogenicity of plaque. PMID- 11780226 TI - [The expression of cathepsin-D in salivary adenoid cystic carcinoma]. AB - OBJECTIVE: To investigate the relationship between Cathepsin-D(Cath-D) and the prognosis of patients with salivary adenoid cystic carcinoma (SACC). METHODS: The immunoactivity of Cath-D of 52 cases with SACC was determined by immunohistochemistry method (Streptavidin-Biotin method). The relationship between Cath-D and the histological type, clinical stage, local recurrence, distant metastasis of the tumor and survival rate of the patients with SACC were analysed. RESULTS: Statistical analysis showed that the expression levels of Cath D were correlated positively with distant metastasis potential and clinical stage (P < 0.05), and had no significant relation with histological type, local recurrence and survival rate (P > 0.05). CONCLUSIONS: Cath-D can facilitate invasiveness and distant metastasis of SACC; evaluation of Cath-D can act as a predictor of distant metastasis of SACC and direct the clinical treatment. PMID- 11780227 TI - [Clinical evaluation of glutaldehyde resinifying therapy on pulp diseases]. AB - OBJECTIVE: To evaluate clinically the glutadehyde resinifying therapy(GR) on pulp diseases. METHODS: A total of 270 teeth with pulp diseases were divided into GR and formaldehyde resinifying therapy(FR) groups. The latter served as a control. Immediate post-operation reactions, short-term (0.5-1 year) and long-term (2-4 years) results were compared between the two groups. RESULTS: Ratio of post operation pain for GR group was 10.2%, while 19.8% for FR group. The difference was statistically significant (P < 0.05, by chi 2 test). The short-term successful rates were 85.4% and 84.9% for GR and FR groups, respectively, whilst the long-term rates were 92.0% and 90.8%, respectively, there were no significant differences between the two groups statistically. CONCLUSIONS: GR could obtain similar clinical results as FR, and has an advantage of lower rate of post operation pain compared with FR. PMID- 11780228 TI - [Cytomegalovirus infection and the changes of T-lymphocyte subsets in RAU patients]. AB - OBJECTIVE: To study the quantitative changes of the T-lymphocyte subsets in RAU patients with different stages and to know the influences of cytomegalovirus(CMV) on cellular immunity in RAU patients. METHODS: CD4(helper/inducer) and CD8(suppressor/cytotoxic) cells in the peripheral blood were tested with monoclonally immunocytochemical technique (APAAP method) in 26 ulcerative stage patients and 10 inactive patients. RESULTS: The percentages of CD4 and CD8 cell were 36.19% and 29.38% respectively in ulcerative stage. The ratio of CD4/CD8 was 1.28 and it was inverted (< 1.0) in 26.92% of the patients. The percentages of CD4, CD8 cells was 39.90% and 34.21% in inactive stage respectively. The ratio of CD4/CD8 was 1.17. The number of CD4 and CD8 cells in ulcerative stage and CD4 cells in inactive stage was significantly lower than the normal values, P < 0.05. The number of CD8 cells in inactive stage was not significantly different compared with the normal value. However the numbers of CD3(total T cells), CD4 and CD8 cells increased to some extent in inactive stage. CD4 cells was significantly lower in 11 human cytomegalovirus (HCMV) DNA positive patients than that in 9 HCMV DNA negative patients (P < 0.05). CONCLUSIONS: A permanent disorder of cellular immunity was an important part of pathogenesis in RAU. CMV infection may be an important factor resulting in the disorder of cellular immunity because of the imbalance of T lymphocyte subsets. PMID- 11780229 TI - [Localization of endothelin-1 in biopsies from oral submucous fibrosis: immunoelectron microscopic study]. AB - OBJECTIVE: To determine the endothelin-1 (ET-1) immunoreactivity in biopsies from human oral submucous fibrosis (OSF) and to investigate the relation between ET-1 and OSF. METHODS: The localization of ET-1 in biopsies from OSF was observed with immunoelectron microscopic techniques. RESULTS: High-density deposits existed predominantly in the cytoplasm of epithelial cells, fibroblasts and endothelial cells, but not found in the biopsies of normal controls. In the biopsies of OSF, high-density granules were lined on the cell membrane, possibly on the rough endoplasmic reticulum and the mitochondria of the epithelial cells and of the fibroblasts. But a few granules were seen in the cytoplasm of the endothelial cells of microvesseles. CONCLUSION: ET-1 is one of the pathogenetic factors of OSF. PMID- 11780230 TI - [Micro-anatomy of the apical lateral foramina of permanent teeth]. AB - OBJECTIVE: To provide data of apical lateral foramina of Chinese people's permanent teeth. METHODS: The shape and diameter of the apical lateral foramina in 1,502 permanent teeth were observed under the XTL-2 stero-microscope. RESULTS: The shape and diameter of 230 apical lateral foramina in the permanent teeth can be divided into four types: round (61.31%, diameter: 0.09-0.26 mm), oval (36.96%, diameter: 0.12-0.28 mm), renal (1.30%), and irregular (0.43%). The occurrence of the apical lateral foramina is 15.31% (230/1,502). CONCLUSIONS: The apical lateral foramina are found in 1/7 of 1,502 permanent teeth. PMID- 11780231 TI - [Analysis of facial profile preferences among the Chinese population]. AB - OBJECTIVE: To determine the preferences of Chinese population for facial profile esthetics. METHODS: 400 panelists were randomly selected from Chinese cultural and educational backgrounds. Subjects were asked to rank the five distinct facial profiles of yellow race in descending order of attractiveness. RESULTS: The ranking was as follows: B, A, E, D, C. The differences in rank scores among all the profile types were statistically significant (P < 0.05). CONCLUSIONS: 1. Given a choice between an orthognathic or a more retrusive profile, Chinese public tended to prefer the latter; 2. The preferences for facial profile esthetics were not influenced by sex, age and educational level. PMID- 11780232 TI - [Shear bond strength of glass ionomer cement for orthodontic bracket bonding]. AB - OBJECTIVE: The purpose of this study was to investigate the shear bond strength of resin-modified glass ionomer used for orthodontic bracket bonding. METHODS: 30 extracted premolars were evenly divided into two groups. Edgewise brackets (Orsu) were bonded with resin-modified glass ionomer (Advance) in group one and with composite resin (DM) in group two. The shear bond strengths of two materials were tested by material testing machine after 24 hours. The adhesive remnant index was scored after debonding. RESULTS: The shear bong strengths of resin-modified glass ionomer and composite resin were (6.862 +/- 2.142) MPa and (7.183 +/- 3.205) MPa respectively. There were no statistically significant differences between two groups. CONCLUSIONS: In vitro bond strength of resin-modified glass ionomer had reached the same level of composite resin. It had the prospect of clinic use. PMID- 11780233 TI - [Development of a video system for three-dimensional cephalometry and dental cast analysis]. AB - OBJECTIVE: The purpose of this article is to introduce the outline of our newly developed video system for three-dimensional cephalometry and dental cast analysis. METHODS: The video measuring technique was utilized in the field of dentistry in our study. Two CCD cameras were used to capture the images both of the dental cast and headfilms. The dental cast analysis and three-dimensional cephalometry shared a set of operating system. The three-dimensional reconstruction was based on the LAT and PA films. RESULTS: The measurement error of dental cast analysis is less than 0.09 mm, and the error of three-dimensional cephalometry is less than 0.45 mm. CONCLUSIONS: The clinical application suggests that the use of our system is feasible not only for clinical evaluation of malocclusion but also for saving time necessary for treatment planing and diagnosis. PMID- 11780234 TI - [The role of IL-1 beta and TNF-alpha in hyper-reactivity of neutrophils in rapidly progressive periodontitis patients]. AB - OBJECTIVE: Neutrophils (PMNs) from rapidly progressive periodontitis (RPP) was found to generate abnormally high levels of oxygen radicals. Elastase activity in gingival crevicular fluid (GCF) from RPP was also found much higher. It suggested that PMNs in some RPP patients are hyper-reactive. The purpose of this study was to investigate the mechanism of PMN hyper-reactivity by surveying the correlation of TNF-alpha level with elastase activity in GCF and by evaluating the association between PMN infiltration and the expression of IL-1 beta and TNF alpha in gingival tissues from RPP patients. METHODS: 41 GCF samples from 22 RPP patients and 34 GCF samples from 11 healthy controls were collected. The total amount of TNF-alpha in GCF was detected using ELISA. The elastase activity was measured with a low molecular weight substrate (S2484) specific for granulocyte. The correlation of TNF-alpha level with elastase activity in a GCF sample was analyzed with Spearman correlation. 20 gingival specimens were obtained respectively from 10 RPP patients and 5 periodontally healthy controls. The expression of IL-1 beta and TNF-alpha was detected with immunohistochemistry. The distribution of PMN was observed with hematoxylin and eosin staining. RESULTS: Total amount of TNF-alpha in GCF was positively correlated with elastase activity (r = 0.44, P < 0.05). The IL-1 beta- and TNF-alpha-positive cells in gingiva were superimposed in areas where PMNs infiltration predominant. CONCLUSION: The hyper reactivity of PMN in RPP patients was related to locally produced IL-1 beta and TNF-alpha. PMID- 11780235 TI - [Effect of recombinant human bone morphogenetic protein-2 on the expression of osteopontin in human periodontal ligament cells]. AB - OBJECTIVE: To investigate the effects of growth factor rhBMP-2 on the expression of osteopontin in periodontal ligament cells(PDLC). METHODS: In culture model of human PDLC, in situ hybridization method was used to detect the expression of osteopontin in human PDLC. RESULTS: The PDLC showed negative reaction to express osteopontin, while those PDLC stimulated by rhBMP-2 showed osteopontin mRNA positive reaction in plasm. CONCLUSION: rhBMP-2 can induce the expression of osteopontin in PDLC. rhBMP-2 may be an effective growth factor in stimulating PDLC differentiation to osteoblast and promote periodontal regeneration. PMID- 11780236 TI - [Effect and mechanism of garlic juice and hydrogen peroxide on the degradation of lipopolysaccharide]. AB - OBJECTIVE: To elucidate the effect and mechanism of garlic juice and hydrogen peroxide on the degradation of lipopolysaccharide (LPS). METHODS: Hot phenol water method, phenol-chloroform-petroleum ether procedure, limulus lysate test, lowry's ash spetrographical examination and gas-liquid chromatography etc. were used in this study. RESULTS: The sequence of degradation effect was 30% hydrogen peroxide (H), the most powerful, followed by garlic juice (G), 1:1 diluted G and 3% H, their effects were dose dependent and G group was time dependent. The mechanism of H on LPS degradation was fractionization of phosphoryl in position 1 from lipid A, while that of G was complex, it could bound LPS molecule and influenced its effect besides LPS hydrolysis. CONCLUSION: The study may imply that the degradation position and mechanism on LPS are different and remain to be elucidated. PMID- 11780237 TI - [The effect of non-surgical periodontal and adjunctive minocycline-HCL treatments on collagenase activity]. AB - OBJECTIVE: To evaluate the effect of scaling and root planing combined with local application of 2% minocycline hydrochoride ointment(Periocline) on the level of collagenase activity releasing from PMNs in GCF. METHODS: This was a randomized, single-blinded, split mouth design study. The target sites of 31 patients with moderate to severe periodontitis (PD > 5 mm) was randomized by left-side and right-side into one of the two groups (the test group and the control group). Subsequently each patient was scheduled for two appointments for the full-month supra-gingival scaling and oral hygiene instruction. At baseline all patients received subgingival scaling and root planing and were followed by 4-time applications of Periocline with one-week interval for totally four weeks in the test group. All patients were taken GCF for measuring collagenase by the method of Nakashima et al (1996) and were examined based on four parameters, including plaque index, pocket depth, attachment loss and bleeding on probing. RESULTS: Four weeks after root planing with 4-time applications of Periocline, all clinical parameters and active collagenase in GCF decreased significantly in the test groups[(593 +/- 112) mU/sample vs (311 +/- 98) mU/sample, P < 0.001]. On the other hand, simple root-planing therapy had limited effect on the active collagenase[(611 +/- 123) mU/sample vs (523 +/- 127) mU/sample], although all clinical parameters were also reduce significantly. Interestingly, seven weeks later, gingival inflammation and the active collagenase were reduced more significantly than those after four-week root planing in both groups[Test: (311 +/- 98) mU/sample vs (207 +/- 57) mU/sample; CONTROL: (523 +/- 127) mU/sample vs (345 +/- 117) mU/sample, P < 0.001]. At eleven week, gingival inflammation and the level of collagenase activity were rebounded in the control group[(467 +/- 108) mU/sample]. However, in the test group they were kept in lower level[(213 +/ 121) mU/sample]. The level of collagenase activity showed significantly positive correlation with GCF volumes and AL in two groups. CONCLUSION: These results indicate that local application of 2% minocycline hydrochoride ointment may effectively inhibit the level of active collagenase from PMNs and may inhibit connective tissue breakdown by inhibiting neutrophil collagenase. PMID- 11780238 TI - [A clinical investigation on miniplate fixation as tension band for mandibular angle fracture]. AB - OBJECTIVE: To investigate the clinical application of miniplate as tension-band in fixation of mandibular angle fractures. METHODS: The miniplate fixation as tension-band was used in 27 cases and 28 sites of mandibular angle fracture, another 19 cases of mandibular angle fracture involving 20 sites were fixed at the lower border by using universal plate(14 sites), compression plate(4 sites) and double miniplate(2 sites). The tension-band fixation group contained: unfavorable fracture line 82%, serious displacement 25%, extraction of tooth simultaneously at reduction 55%. In lower border fixation group, there were 95% of patients with unfavorable fracture line, 85% had serious displacement, and 33% had tooth removed. The follow-up rate was 89% with a mean period of 36 weeks in the tension-band group and 79% with a mean period of 31 weeks in lower border group. RESULTS: Infection occurred in 10.71% of tension-band group and 5% of lower border group, and mild malocclusion appeared in 7.4% and 5.26% respectively. Additionally, 21.43% of the tension-band group had a healing gap at lower border. CONCLUSIONS: The use of miniplate for the tension-band fixation is effective for the favorable and slightly displaced mandibular angle fractures, the augmentation of fixation at lower border was necessary for unfavorable and seriously displaced fractures. PMID- 11780239 TI - [The expression of RAR beta mRNA in rat tongue carcinogenesis]. AB - OBJECTIVE: To elucidate the relationship between the expression of nuclear retinoic acid receptor beta (RAR beta) mRNA in oral carcinogenesis and squamous cell aberrant differentiation. METHODS: A total of 69 rat tongue carcinogenesis specimens induced by 4-nitroquinoline-1-oxide (4NQO) were detected for RAR beta mRNA by in situ hybridization. RESULTS: With the progress of tongue carcinogenesis and epithelium cell disdifferentiation, the expression of RAR beta mRNA was down-regulated. The positive rate of RAR beta mRNA in normal, hyperplasia, mild-moderate dysplasia, severe dysplasia, in situ carcinoma and squamous cell carcinoma was 100.0%, 87.5%, 75.0%, 72.2%, 45.5% and 18.8%, respectively. CONCLUSIONS: The down-regulation of RAR beta mRNA may be associated with the epithelium cell aberrant differentiation and may be an important molecular mechanism of oral carcinogenesis. PMID- 11780240 TI - [Effects of various growth factors on human mandibular condylar cartilage cell proliferation]. AB - OBJECTIVE: To investigate the effects of transforming growth factor-beta 1 (TGF beta 1) insulin-like growth factor I (IGF-I) and basic fibroblast growth factor(bFGF) on human mandibular condylar cartilage (MCC) cell proliferation. METHODS: Isolated human MCC cells were cultured in DMEM supplemented with 10% newborn calf serum(NCS). The second passages were used in order to avoid chondrocyte dedifferentiation. Cells were seeded at 2 x 10(4)/well on 96-well plate. After synchronization, medium was replaced by DMEM containing 0.4% NCS or 10% NCS with various growth factors, concentrations and combinations. Dose response and time-course were studied by MTT colorimetric method. RESULTS: In 0.4% serum containing medium, bFGF stimulated the proliferation moderately, whereas TGF-beta 1 and IGF-I had less effect. In 10% NCS condition, all three growth factors had mitogenic effect and acted dose-dependently. The effects were significant after three days. Among them, bFGF was a potent mitogen(increased by 65%), IGF-I the next(24%). The effect of TGF-beta 1 (13%) might be mediated by some other factors in the serum. The synergetic effects were achieved when they were used in combination. CONCLUSION: It is suggested that optimal combination of growth factors can promote the proliferation of MCC cells significantly, this might be an ideal way in dealing with cartilage damage during pathogenesis. PMID- 11780242 TI - [Effect of lost bite force on the expression of bFGF in rat molar periodontal ligament]. AB - OBJECTIVE: To observe the dynamic change of the expression of basic fibroblast growth factor (bFGF) in rat molar periodontal ligament(PDL), combined with other experiments to probe into the relation of the expression between bFGF and type I collagen mRNA. METHODS: Animal model was established by extracting the left maxillary molars. Immunohistochemistry was applied. RESULTS: The expression of bFGF obviously increased from the first day to the second week (P < 0.05), Came back to that of normal bite force group at the third week. There were strong negative relative relationship between the expression of bFGF and that of type I collagen mRNA. CONCLUSION: The expression of bFGF increased under lost bite force in rat molar PDL. The effect of bite force on the expression of PDL type I collagen mRNA is closely related to the expression of bFGF. PMID- 11780241 TI - [Expansional limitation of facial nerve: an experimental study on rabbits]. AB - OBJECTIVE: To investigate expansional limitation of facial nerve. METHODS: Buccal branches of rabbit facial nerves were transected middly and the proximal and distal nerve stumps were lengthened separately by the expander which was designed by the authors. According to the principle of orthogonal design, 25 proximal and 25 distal stumps were lengthened up to 0%, 10%, 20%, 30%, 40% respectively. The average speed of the elongation was 10 mm per 10 minutes. After the elongation were finished, end to end neurorrhaphy were performed except the 0% group in which 10 mm of the nerve wascut off and then retransplanted. Fifteen weeks later, electromyogram(EMG) of buccal muscle and nerve conductive velocity(NCV) were measured to evaluate the function of repaired nerves. While, the number and diameter of regenerating fibers were counted. RESULTS: Compair Compare to the transplantation group, when the proximal segments were lengthened up over 30%, the result of the repairment would be effected considerably despite the elongation of the distal segments, and when the proximal segments were elongation within 30%, the distal segments could be lengthened up to 40% without significant decrease in the functional index (EMG, NCV). CONCLUSIONS: Deducting the postexpansional retraction, the elongation limit of the proximal segments is 18.7% +/- 2.4%, while the distal segments is 24.9% +/- 2.5%. These should be a referable indications for peripheral nerve especially for facial nerve defect reconstruction. PMID- 11780243 TI - [Clinical pathological analysis of clear cell odontogenic carcinoma]. AB - OBJECTIVE: To investigate clinical pathological characteristics and biologic behavior of clear cell odontogenic carcinoma. METHODS: Analysis of clinical data, microscopic and electromicroscopic observation of 8 cases of clear cell odontogenic carcinoma. RESULTS: The tumor occurred mainly in female and involved right mandible. 37.5% had regional lymph node metastases at the time of operation. Recurrence rate was 33.3%. The tumor had no capsule and consisted of clear cell and basaloid cells which arranged in nests and strands. Tumor cells often grew close to the blood vessels and caused bone resorption. There were less cell organelle and swelling of mitochondria. CONCLUSION: This tumor belongs to middle grade malignant tumor and should be called clear cell odontogenic carcinoma. PMID- 11780244 TI - [Effects of the occlusal splint on stress distribution of the mandible with temporomandibular joint disorders]. AB - OBJECTIVE: To investigate the biomechanical mechanism of occlusal splint therapy of temporomandibular joint disorders (TMD). METHODS: The changes of stress distribution on the mandible with TMD before and after occlusal splint therapy were simulated and analyzed by three-dimensional finite element method. RESULTS: Occlusal splint influenced the character of stress distribution on the mandible. It might distinctly decrease maximum and minimum principal stresses on each region of the mandible with TMD, among which the stress on condylar surface of ill side was reduced more significantly, and the stress distribution of bilateral condyles was close to equality and balance. Meanwhile, the stress symmetry on every position of the mandible was improved slightly. CONCLUSIONS: Occlusal splint can alleviate even eliminate the injury to the temporomandibular joint, and make unbalance of joint inner environment adjusted and restored by improving the stress distribution. This is primarily thought to be one of the main biomechanical mechanism of occlusal splint treatment. PMID- 11780245 TI - [The effects of experimental osteoporosis on bone tissues around hydroxyapatite implants]. AB - OBJECTIVE: To investigate the effects of estrogen decreasing on bone tissues around implants in ovariectomized rats. METHOD: Forty-two female Wistar rats, aged 32 weeks, were used in this study. First, cylindrical hydroxyapatite-coated implants were planted in the proximal part of tibiae of the rats. Then, the rats in experimental group and control group were respectively performed ovariectomy and false surgery after 56 days, the rates were killed in 28, 84 and 168 days after operation, and tibiae were taken out to prepare undecalcified sections. The section were examined by routine histomorphometric measurement and the dynamic changes of trabecular bone and extent of contact between the implants and bone tissue around them. RESULTS: Twenty-eight days after operation, the density of trabecular bone around the implant in experiment group was found significantly reduced compared with the control group. In the area of cortical bone, no difference was found in the extent of implant-bone contact between two groups, while in the area of spongy bone the extent of contact was different obviously. CONCLUSION: Ovariectomy in Wistar rats can induce significant osteoporosis around implant, these finding suggest that menopause in women patients may also induce osteoporosis around implanted artificial teeth and affect the prognosis. Therefore, the patients should be carefully observed during the implant treatment course. PMID- 11780246 TI - [The study of histopathology and bacteriology of coronal pulp tissue in deciduous teeth with deep dentin caries]. AB - OBJECTIVE: To study the status of coronal pulp of deciduous teeth with deep caries and causes of pulpal histopathological changes. METHODS: 45 deciduous molars with occlusal deep caries were selected at random. The patients did not receive any antibiotic for one month. The coronal pulpal histopathology was observed with optical microscopic technique. The bacteria in pulp chamber were cultured by the ways of aerobic and anaerobic culture technique. The dentinal tubular structures and bacteria within the tubules of cavity basal part dentin were studied with scanning electron microscopic technique. RESULTS: Coronal pulp tissue of 77.8% of deciduous teeth with deep caries showed chronic inflammation to various degrees or chronic pulpitis with acute attack. There were aerobic and anaerobic mixed infection in pulp chambers of 94.9% deciduous teeth with deep caries. It was found that coccus and bacillus invaded into dentinal tubules of cavity basal part. Coccus located inside tubules with intact tubular walls, while tubular walls were destroyed the bacillus was present. CONCLUSION: There are aerobic and anaerobic mixed infection in pulp chamber of deciduous teeth with deep caries. The coronal pulp tissue shows chronic inflammation to various extent in over 2/3 deciduous teeth with deep caries. Bacillus has stronger destructive power to dental tubules. PMID- 11780248 TI - [Morphometrical study on the development of the trisomy-18 with cleft palate and euploid mice]. AB - OBJECTIVE: To quantitatively compare the whole body, the lateral maxillofacial profile in Ts18 foetuses with cleft palate (Ts + CP) and euploid foetuses in order to answer the question whether this animal model is associated with maldevelopment or hypoplasia of the craniomaxillofacial region. METHODS: Sixty female Hanmice and 11 male mice with the Rb(2.18) 6Rma and Rb(1.18) 10Rma chromosomes were used to generate 569 living foetuses. Of these, 52 pairs Ts + CP and euploid foetuses were selected according to about equal body weight, and used in gross morphometric study. RESULTS: Ts + 18 foetuses had greater body flexion, a significant maxillary and mandibular retrusion, also mandible in Ts + CP foetuses were smaller than in euploids without cleft. CONCLUSIONS: This animal model of congenital cleft palate developed hypoplasia of the maxilla and mandible. PMID- 11780247 TI - [Long-term evaluation of bilateral alveolar bone grafting]. AB - OBJECTIVE: To evaluate the long-term result of the bilateral alveolar bone grafting. METHODS: Fifty-five consecutive complete bilateral cleft lip and palate patients (36 males and 19 females) who had alveolar bone grafting were included in this study. The total number of cleft sites was 110. Cancellous bone from the iliac crest was grafted into the alveolar cleft areas. The cleft sites were studied in two groups according to whether the cleft canine had erupted prior to bone grafting or not. Anterior occlusal radiographs were taken before and after bone grafting. The minimum period of observation after alveolar bone grafting was one year. Criteria described by Bergland et al. (1986) were utilised to assess the height of the interdental septum. RESULTS: The results showed that bone grafting before canine eruption has a higher clinical success rate (95%) compared with that carried out after canine eruption (67%). CONCLUSION: The critical variable affecting the quality of bilateral alveolar bone grafting is the timing of the surgery. PMID- 11780249 TI - [The construction of three-dimensional finite element model of human maxillary complex]. AB - OBJECTIVE: To develop a method to construct three dimensional finite element (3-D FE) model which may express biomechanic dynamic state characters of normal maxillary complex. METHODS: SCT image reconstruction technique, digital image transfer and transcription and 3-D FEM were used in combination with self programming and ANSYS soft ware. RESULTS: A 3-D FE model of normal maxillary complex is constructed. The elements and nodes of the model are 2,602 and 4,595. CONCLUSION: The method to develop a model of maxillary complex adopting SCT 3-D image reconstruction technique, image transfer and transcription, and 3D FEM are feasible and effective. PMID- 11780250 TI - [Quantitative 3D measurements of the skull base by using spiral volumatric CT images]. AB - OBJECTIVE: To study the spatial relationships of mandibular condyle and carotid canal, jugular fossa, foramen ovale, foramen spinosum when mandible in normal physical position. METHODS: 100 native adults were examined by spiral volumatric CT. The data were transferred to workstation, three-dimensional(3d) cranial base images were reconstructed, 3D measurements were performed by using specific 3d CT landmarks. 12 points were defined and 28 distances and angles were measured in the skull base from submandibular viewpoint. The internal pole of condyle and the condylar long axis were regarded as the center point and 0 degree axis in the reference frame. RESULTS: Submandibular approach provided a clear vision of the internal pole of condyle and condylar long axis. The ECC was located at 12.01 +/- 2.71 mm, 5.14 +/- 1.22 degrees, Jug was located at 15.11 +/- 2.72 mm, -56.27 +/- 14.05 degrees according to the reference frame. CONCLUSIONS: Quantitative measurements of 3D skull base can be very precise. Mandibular approach is easy to show the mandibular condyle. The reference frame is helpful to located other important structures of skull base in operation. PMID- 11780251 TI - [Reducing bacterial aerosols by ultrasonic scaling with Koutai or 1.5% H2O2 pre rinse]. AB - OBJECTIVE: To compare the effects of Koutai and 1.5% H2O2 on the bacterial aerosol contamination generated by ultrasonic scaling. METHODS: Aerosol and splatter produced by ultrasonic scaling were collected pre and post rinsing with Koutai or 1.5% H2O2, aerobes and anaerobes were incubated and counted. RESULTS: 737 CFU aerobes and 749 CFU anaerobes were deducted after rinsing with Koutai, 355 CFU aerobes and 419 CFU anaerobes were deducted after rinsing with 1.5% H2O2. Both groups are effective in reducing aerobes and anaerobes CFUs (P < 0.01), although the former was much better than the latter in the reduction of aerobic CFUs in aerosols (P < 0.05). CONCLUSION: Koutai or 1.5% H2O2 risen can significantly reduce aerobic and anaerobic CFU in aerosols. PMID- 11780252 TI - [Experimental study on polyphenol anti-plaque effect in human]. AB - OBJECTIVE: To evaluate anti-caries effect of Chinese green tea's polyphenol. METHODS: 150 volunteers are randomly divided into 3 groups: A, B test group and contrast group, 50 persons in each. People in test groups were given polyphenol's tablet, placebo was given in contrast group, a tablet three times a day. After 3 weeks, group A was given placebo and group B continued polyphenol for 6 weeks. RESULTS: After using polyphenol's tablet for 2 weeks, the plaque index of test groups were evidently lower than the contrast group (P < 0.01). After stopping use of polyphenol tablet, the effect was still kept for 3 weeks. CONCLUSION: It can be concluded that polyphenol tablet from Chinese green tea has evident anti plaque effect. PMID- 11780253 TI - [Experiment study of guiding bone tissue regeneration by frozen homologous periosteum]. AB - OBJECTIVE: Explores the feasibility of guiding bone tissue regeneration by frozen homologous periosteum. METHODS: Rabbit's cranial periosteum was taken and refrigerated. In thirty-one white Japanese big ear rabbits, defects of the mandible were created. Defect at one side was covered with the membrane, another side not. The rabbits were sacrificed on four, eight, twelve, sixteen weeks. Specimens were examined by naked eye, X-ray, and histology. RESULTS: The frozen homologous periosteummet the requirement of guiding bone tissue regeneration There was no rejection, and could be kept 8 for 12 weeks in the body. It had the favorable efficacy of obstructing the fiber tissue from filling into bone defects and had an efficacy of guiding bone tissue regeneration. CONCLUSIONS: Frozen homologous periosteum is a perfect guiding bone tissue regeneration membrane. PMID- 11780254 TI - [Wear study of dental restoration materials with a new study-system in vitro]. AB - OBJECTIVE: To investigate abrasive wear of composite resins in vitro. METHODS: A chewing simulator was used to perform the abrasive wear of four composite resins in vitro and an accurate three-dimensional laser-scanning system was used to measure the abrasion los of the materials. RESULTS: According to worn volumes, the order of five materials is: Enamel < Targis Dentin < Dentacolor < Artglass < Vita Zeta. According to the worn-depthest-points, the order of five materials is: Enamel < Targis Dentin < Artglass < Dentacolor < Vita Zeta. CONCLUSION: Targis Dentin shows no significant difference on ware resistance from human enamel, while three other composite resins are poorer than human enamel. This system in vitro is effective, accurate, quick and economical. PMID- 11780255 TI - [The research and development for dental office information system]. AB - OBJECTIVE: To study how to use the technology of information management, data base and graphics to develop the dental clinic information system. METHODS: Base on the expert's demonstration and investigation, we made up the operative cord of the dental clinic. The PowerBuilder and SQL Anywhere Tools V6.0 was used to develop the information system. RESULTS: There are 7 different sub-functional models in our system, and they are about patients, workers, finance, capital, expandable, technician lab., and maintenance. The system has been used in 8 dental clinics, and about 1,100 cases history were managed. The result showed us that the system has a strong and perfect function for clinical service, and it is easy to be used. CONCLUSION: The system could enhance the user's management level and benefit to patients and clinical service. PMID- 11780256 TI - [Sero-monitoring of notifiable diseases in wild boar in the Netherlands 1999 2001]. AB - Within the framework of a sero-monitoring system, in operation since 1996. blood samples from wild boar shot during the hunting seasons 1999-2000 and 2000-2001 in The Netherlands were screened for the presence of antibodies against classical swine fever virus (CSFV), swine vesicular disease virus (SVDV), and Anjeszky's disease virus (ADV). The results indicate that CSFV, SVDV, and ADV are uncommon in the wild boar population in the Netherlands. Because of the recent foot-and mouth disease (FMD) epidemic in the Netherlands in 2001, blood samples (approximately 200 samples) from wild boar shot in the Netherlands during the hunting season 2001/2002 were examined for antibodies against FMD. To date, antibodies against FMD have not been detected. PMID- 11780257 TI - [Article on progesterone test kits and how far can the conclusions go?]. PMID- 11780258 TI - [Vaccination against foot and mouth disease: a biotechnical approach?]. AB - Described is how through a biotechnical approach a FMD 'marker' vaccine and matching diagnostic test could be developed which makes it possible to control FMD safety and effectively. Much research is still necessary but important in this is that the European Union supports these developments. PMID- 11780259 TI - [First aid in accidents involving large pets]. PMID- 11780260 TI - [Unique identity guarantee with electronic animal identification system]. PMID- 11780261 TI - [Responsibility of employer for car accidents involving employees]. PMID- 11780262 TI - [Disbelief]. PMID- 11780263 TI - [Discussion cooperation on non-vaccine legislation useless?]. PMID- 11780264 TI - [Home visit, home visit!]. PMID- 11780265 TI - Laboratory diagnosis of bacteremia and fungemia. AB - Many of the variables that affect the laboratory diagnosis of bacteremia and fungemia have been addressed in this article. Whereas the scientific basis and principles for blood cultures are well-established, and the methodology has improved, the diagnosis of bacteremia and fungemia still depends greatly on the care that is taken in obtaining the specimens of blood and the skill of the clinician in interpreting positive results. PMID- 11780266 TI - Laboratory diagnosis of community-acquired lower respiratory tract infection. AB - This article has focused on the evaluation of outpatients with lower respiratory illness. In large part, the need for microbiological work-up is host-dependent. Healthy patients usually do well, and laboratory data are often unnecessary. The abnormal host requires a different approach and, in general, the more compromised the host, the more aggressive the laboratory evaluation. A renal transplant patient with respiratory symptoms often follows the dictum that "common things happen commonly;" however, the clinician needs that extra level of assurance in this case. Some transplant patients may have respiratory illness caused by strongyloidiasis. Cystic fibrosis is another example of the need for a more comprehensive laboratory evaluation. Specialized selective media and additional susceptibility studies may be needed to evaluate isolates associated with exacerbation of symptoms in these patients. The clinical laboratory should be forewarned of any materials coming from invasive diagnostic techniques, so they can prepare and offer useful advice regarding specimens, transport, and follow up. Microbiological laboratories are often most knowledgeable regarding what type of testing is appropriate. Direct communication with the laboratory is essential to assure the best patient care. PMID- 11780267 TI - Laboratory diagnosis of central nervous system infections. AB - The laboratory diagnosis of CNS infection is essential for optimal therapy. Acute infection requires rapid turn-around testing with high predictive values, that is, the ability of a test to accurately identify those patients who do or do not have disease caused by a specific etiology. The Gram's stain, fungal stains of direct smears, antigen testing for C. neoformans, and culture of bacteria, fungi, mycobacteria, and some viruses are important tests for the diagnosis of acute infection. The laboratory diagnosis of chronic infection necessitates discussion between the clinician and laboratory technician to allow triaging of testing. Antigen tests for bacteria, fungi, and viruses; antibody tests for multiple microorganisms; and PCR testing for bacteria, M. tuberculosis, and many viruses are all important in limited clinical situations. All testing for acute or chronic disease depends on sufficient specimen that is transported to the laboratory in a manner that will not compromise viability or chemical integrity. Sterile containers that maintain moisture content, exclude oxygen for anaerobic requests, and are stored at proper temperatures (22 degrees C room, 4 degrees C refrigeration, or -20 degrees C freezer depending on pathogen and test) are mandatory. Many laboratory issues addressing the diagnosis of CNS infection are changing or evolving. Most important is the recognition that bacterial antigen testing for the diagnosis of acute bacterial meningitis rarely impacts patient management and is not routinely needed, CSF shunt infections differ from usual meningeal infections and require rapid diagnosis, and TB meningitis remains a difficult disease to diagnosis but may be confirmed first by PCR testing of CSF. In addition, Whipple's disease of the CNS can be confirmed using PCR with CSF; CJD has a marker protein, referred to as 14-3-3 antigen, that can be detected in CSF, and the diagnosis of fungal CNS disease requires careful interpretation of direct smears, antigen and antibody testing, and culture. Most difficult to diagnose among the CNS infections are viral meningitis and encephalitis. The appearance of new etiologies, such as West Nile virus, and the common use of PCR for the herpes viruses and enteroviruses represent important advances. Evolving methods for the laboratory diagnosis of CNS infection represent significant improvements over previous testing; however, the array of tests available demands more attention for appropriate selection, is significantly more expensive, and requires new skills for performance and interpretation. The responsibility for proper use of laboratory testing lies both with the clinician and laboratory technician. PMID- 11780268 TI - Gastrointestinal infections. AB - Advances in public health have reduced the risk of contracting certain enteric diseases, but many remain, and new pathogens have emerged and/or recently have been discovered. The pathogenic agents are varied and consist of a variety of bacteria and select viruses and parasites. Selected use of microbiologic assays to detect these pathogens is encouraged. When tests are ordered non-judiciously, costs rapidly accrue. The age of the patient, time of year, travel history, and clinical presentation all provide clues to the etiologic agent. Microbiologic assays should be used judiciously to confirm or exclude the likely infectious agents. PMID- 11780269 TI - Laboratory diagnosis of viral hepatitis. AB - Both serologic and molecular assays are useful in the diagnosis of viral hepatitis. They may detect early infections before other signs of disease appear, differentiate acute from chronic infections, and detect persistence of viremia or verify development of immunity. Molecular assays may also be used to monitor responses to antiviral therapy, and in the future, be a primary method to screen blood and organ donors (NAT). EIA serologies are used to diagnose acute HAV infections or establish immune status. Similar immunoassays are used to detect HBV infections, verify persistence of antigenemia and degree of infectivity, and indicate immunity (including the response to vaccination). HBV molecular assays can shorten the diagnostic window period, verify persistence of viremia, including monitoring response to antiviral therapy, and be useful in NAT screening of donors. Molecular assays play a major role in HCV diagnosis where serologic tests can document past or present infection but cannot differentiate one from the other. A variety of molecular tests can be used as sensitive (and early) detectors of viremia (and serve as confirmatory tests for positive serologies and as donor NAT methods), document its persistence as an indicator of chronic infection, and monitor responses to antiviral therapy. Both qualitative and quantitative molecular assays are available, and their efficient use requires familiarity with the sensitivity and dynamic ranges of each method. PMID- 11780270 TI - Agents of bioterrorism. Preparing for bioterrorism at the community health care level. AB - Bioterrorism preparedness is clearly a goal for the health care community, working in concert with city, county, state, and federal public health and emergency authorities and in collaboration with law enforcement at the local and federal levels. Opening the channels of communication between all groups involved, obtaining the necessary resources, and maintaining an understanding of the potential agents and the diseases they cause will foster a smooth transition to a rational program directed at patient, personnel, and community safety. PMID- 11780271 TI - Principles of molecular microbiology testing methods. AB - Molecular testing methods have the potential to replace many conventional microbiology laboratory assays. Recent refinements in technology have resulted in more user-friendly testing platforms. These platforms are automated and have lowered risks for contamination, decreased costs, and are faster than older platforms. The success of these technologies depends on their successful application to patient care. Quality issues include appropriate specimens for analysis, performance characteristics of different analytical methods, optimal specimen processing, the effects of PCR inhibitors, and false-positive results caused by contaminating nucleic acids. Quality control guidelines for molecular microbiologic diagnostic assays are in their infancy and require further development. Additionally, the problem of "too much" sensitivity (brought on by the extreme sensitivity of these techniques coupled with the potential presence of small numbers of pathogenic organisms in asymptomatic individuals) should be considered. Potential problems when monitoring therapy (because molecular detection techniques do not generally have the ability to determine whether an organism is dead or alive) can also occur. Cost-effective test use, pathogen- or disease-targeted algorithms, and standardized methods will be necessary for the true value of these technologies to be realized. This is especially important, because, unlike traditional culture methods, most molecular microbiology methods are pathogen-specific. Clinicians familiar with the reasons why "pan-culture" (i.e., requesting all culture possibilities at once) is inadvisable should not use the same irrational approach when requesting molecular tests. The clinical usefulness of molecular testing will be maximized as targeted algorithms are developed and an understanding of molecular test ordering patterns is realized. Laboratory technicians and physicians must continue to apply and combine theories of traditional microbiology, clinical chemistry, and general medicine to the understanding and application of molecular diagnostics. PMID- 11780272 TI - Susceptibility testing. Phenotypic and genotypic tests for bacteria and mycobacteria. AB - Genotypic-based methods hold promise for the rapid and accurate detection or confirmation of antimicrobial resistance; however, phenotypic methods will continue to have an advantage when resistance to the same antimicrobial agent may be caused by several different mechanisms. The diversity of genetic mechanisms may exceed the capabilities of current molecular technology. Genotypic assays have the ability to detect resistance but not susceptibility. Although resutls can be obtained rapidly, many molecular methods are labor-intensive, expensive, and lack standardization. Clinical studies will be required to validate the genotypic approach to detection of antimicrobial resistance. Molecular assays are also at risk for false-positive results because of contamination of specimens by other specimens that carry the DNA targeted for the assay, or carryover of amplified target DNA (amplicons) from a previous PCR assay during sample preparation. Detection of certain genetic resistance loci in clinical specimens must be interpreted with caution, because organisms in normal flora may also harbor the same loci. All these factors must be taken into consideration when introducing a genotypic method in the clinical laboratory. Other considerations include cost, turnaround time, and assay performance. It must be emphasized that the bedside assessment of the patient should always be considered in addition to the results of antimicrobial susceptibility tests (whether phenotypic or genotypic) so that the best outcome is assured for the patient. PMID- 11780273 TI - Antifungal susceptibility testing. New technology and clinical applications. AB - The state of the art for susceptibility testing of yeasts is comparable with that of bacteria. Standardized methods for performing antifungal susceptibility testing are reproducible, accurate, and available in clinical laboratories. The development of quality control limits and interpretive criteria for a limited number of antifungal agents provides a basis for the application of this testing in the clinical laboratory. A proficiency testing program is available as a quality assurance measure for laboratories and has documented steady improvement among laboratories using the NCCLS method. As with antibacterial agents, surveillance programs are now in place using reference quality testing methods to monitor antifungal resistance trends on a global scale. It is clear that antifungal susceptibility testing can predict outcome in several clinical situations. Susceptibility testing is most helpful in dealing with infection caused by non-albicans species of Candida, and susceptibility testing of azoles is increasingly important in the management of candidiasis in critically ill patients. Susceptibility testing also has been standardized for filamentous fungi that cause invasive infections. Studies are ongoing to further refine this approach and evaluate the in vivo correlation with the in vitro data for molds. Future efforts must be directed toward establishing and validating interpretive break-points for licensed antifungals such as amphotericin B, and for new antifungals that are not yet licensed. Finally, procedures must be optimized for testing non-Candida yeasts (e.g., C. neoformans) and molds. PMID- 11780274 TI - Susceptibility testing. Viral pathogens. AB - The control of the global expansion and proliferation of the AIDS pandemic has been complicated by the emergence of resistant strains of HIV-1 to the many new antiviral drugs directed to the genes coding for reverse transcriptase and protease enzymes of the virus. Similarly, new drug regimens for the management of chronic hepatitis B and C infections have been complicated by the lack of sustained clinical responses recently associated with either nucleotide mutation (HBV) or specific genotype of the virus (HCV). Commercial systems for performing and interpreting genotypic analysis will facilitate the recognition of informative mutations, standardize results between laboratories, and produce informative and interpretative result formats for optimal treatment of patients. Drug-resistant strains of herpesviruses (HSV, VZV, CMV) are generally associated with prolonged treatment of these infections in immunocompromised patients. Ultimate relevance of genotypic assays for routine clinical practice will require correlation with phenotypic results and the outcomes of long-term studies associating clinical improvement with antiviral drugs with specific mutation patterns of these viruses. PMID- 11780275 TI - Diagnosis and approach to poisoning in the horse. AB - Poisoning in the horse can present a highly complex case. The practitioner, owner, toxicologist, and pathologist play important roles, and all contribute information that may be important to the case. Once all the information is available, all the evidence is collected (historical, clinical, pathologic, and analytic), and proper sampling of specimens has occurred, a complete summary of the findings can be provided to the client. Based on identification of a potential toxic source and, ultimately, the diagnosis, specific treatment of affected animals and prevention of additional cases can be initiated. Consultation with a veterinary toxicologist aids in the follow-up of a poisoning case and can help to provide a thorough background to assist in preventing reoccurrence. PMID- 11780276 TI - Handling forensic necropsy cases. AB - Immediately record the findings. A tape recorder would be excellent for this. If none is available, findings should be written down as soon as possible before memory of the examination fades. It is important to record comments on every organ that you examined. Three years from now in a court deposition, it may be difficult for the practitioner to remember if he looked at the adrenal glands or if there was no gross evidence of hyperplasia. When writing a report, it is a good idea to describe the tissue changes rather than just to give an interpretation. An example of the latter would be, "The horse had a severe pneumonia." A better method might be, "The horse's lungs had a bilaterally symmetric pneumonia in the ventral portions of the anterior, middle, and diaphragmatic lung lobes. This pneumonia accounted for roughly 45% of the total lung area. These pneumonic areas were dark red, sunken, and firm with a dull granular pleura. When cut, there was a yellow exudate that exuded from the cut surface." This latter description gives good evidence of why it was believed that the lung was pneumonic and just how severe the change was. Several years from now, the latter description does more to refresh the memory of the case. Carefully label and preserve the specimens for later diagnostic tests. List all the fresh samples collected. Time spent on these details now can save you considerable embarrassment later. Following these suggestions should allow the practitioner to provide the best possible service to all parties involved. PMID- 11780277 TI - Epidemiology for the equine practitioner. AB - In this article, I have discussed the principles and methods of outbreak investigation, reinforcing important concepts with examples from the veterinary literature. The approach presented is applicable to outbreaks caused by any agent whether it is infectious versus noninfectious or contagious versus noncontagious. The solutions vary. The experience of others presented with similar situations may be especially helpful. Because of their nature, outbreaks are difficult to prepare for. When faced with a potential outbreak, the best strategy is to approach it scientifically, systematically, and with an open mind. PMID- 11780279 TI - Adverse drug reactions and interactions in the horse. AB - Drugs undergo extensive evaluation before they are marketed. The occurrence of adverse reactions, however, may be so rare that thousands of patients must receive the drug before reliable data are available. It is necessary that veterinarians be informed about the drugs they use, be able to recognize drug associated complications, know how to evaluate the patient for evidence of drug associated toxicity, report adverse effects of drugs to the respective manufacturers, and be prepared to provide medical support and antidotal treatment (if it exists) for a patient if toxicosis occurs. PMID- 11780278 TI - Residues and considerations for use of pharmaceutics in the performance horse. AB - Analytic chemistry laboratories responding to the concerns of the industry over drug use and abuse in performance horses should continue to develop more sensitive methods of drug detection. The unwanted result of this increase in sensitivity is the detection of therapeutic medications days to weeks after administration. The adoption of decision or threshold concentrations for residues of nonpermitted medications should allow laboratories to focus their efforts on drugs of abuse in the performance horse industries and permit veterinarians to provide appropriate medical care to these equine athletes. PMID- 11780280 TI - Risks associated with the use of herbs and other dietary supplements. AB - The use of dietary supplements (herbs, vitamins, minerals, amino acids, enzymes, and other compounds) is common in horses. They are heavily marketed in retail stores, magazines, and on the Internet. There is the perception that since these compounds are "natural" they are devoid of toxicity, and, therefore, they are safe to use. Some of the active compounds in supplements, however, have inherent toxicity, and using them may cause adverse effects. Even relatively non-toxic ingredients may be toxic if used over-zealously or for a long period of time. By and large, these compounds have not been tested for safety or efficacy when used as marketed, and, unfortunately, there is little regulatory oversight for such products. Other deleterious consequences of dietary supplement use include interaction of compounds in the products with conventional drugs, resulting in unexpected adverse effects, or the occurrence of violative residues in urine samples collected from show or performance horses. This article provides a brief overview of potential problems associated with dietary supplements, primarily focusing on products containing herbs and essential oils. PMID- 11780281 TI - Toxic feed constituents in the horse. AB - Poisoning cases in horses associated with dietary exposures can encompass a wide variety of etiologies that can be caused by natural or man-made components. Feed mixing errors and ingestion of feed formulated for other species are the most common means by which poisonings from man-made materials occur. Ionophore feed additives and antibacterial agents are especially toxogenic to horses. Effects of ionophores in horses include clinical, clinicopathologic, and pathologic changes associated with cardiac, muscular, and neurologic tissues involvement. The acute effects of ionophores, however, can result in long-term cardiac dysfunction. Antibacterial effects are associated with changed microbial populations in the digestive tract that results in bacterial toxin liberation. These bacterial toxins damage the mucosa, and they result in systemic effects. For either type of feed-associated poisoning, it is critical that samples be analyzed for an accurate diagnosis. PMID- 11780282 TI - Pesticide toxicosis in the horse. AB - Toxicosis from pesticides rarely occurs in horses and is usually the result of inappropriate pesticide use or handling by humans. Organophosphorus and carbamate insecticides inhibit acetylcholinesterase and are the insecticide class most frequently associated with toxicosis in domestic animals. Metaldehyde is a molluscicide, and zinc phosphide is a rodenticide, both of which have caused toxicosis in horses. All three of these pesticides affect the nervous system of horses and can be fatal if not treated promptly. PMID- 11780283 TI - Industrial chemicals and the horse. AB - Poisoning resulting from exposure to a wide variety of industrial chemicals is not a common occurrence in horses, but it does happen on occasion. A wide range of toxicosis can occur from a wide range of industrial pollutants, such as dioxin, carbon tetrachloride, and tetrachloroethylene, to heavy metals, such as cadmium and zinc. The equine practitioner must consider industrial chemical toxicosis in differential diagnoses and work with a reputable veterinary diagnostic laboratory to confirm or rule out industrial chemical poisoning. PMID- 11780284 TI - Metal toxicosis in horses. AB - The ubiquity and stability of metals in the environment make them unique as a pollutant or an essential dietary component. Metals are neither created nor destroyed by chemical processes but are redistributed in the environment. In combination with other elements, metal compounds and alloys are essential materials of the contemporary world. Inappropriate use or distribution in the environment leads to adverse health effects on all biologic systems, including horses. Gastrointestinal upset is a common feature of acute toxicosis with metals in general. Among the metals discussed, arsenic and inorganic mercury have a propensity to do severe damage to the gut. Deposition of cadmium on forage is the source most likely to intoxicate horses. This subchronic to chronic problem in horses is manifest as disease of the musculoskeletal system and kidneys. Iron containing hematinics are widely used in racetrack horses and occasionally result in hepatopathy when excessive doses are administered. Lead continues to be recognized as the most significant environmental metal pollutant. Poisoning is encountered routinely in humans and animals. Of the animal species of veterinary concern, lead-poisoned horses are not a frequent encounter. Lead-intoxicated horses show signs of peripheral neuropathy (laryngeal hemiplegia), intermittent colic, and mild anemia. Acute mercury poisoning sometimes occurs from the common use of mercury-containing blistering agents, with most clinical findings related to acute renal failure. Chronic excessive intake of zinc by horses is uncommon but devastating in rapidly growing foals. The mechanism of chronic zinc toxicosis is coupled to the induced copper deficiency. The condition is a disease of cartilage in the articular and growth physes. PMID- 11780285 TI - Toxic plants. What the horse practitioner needs to know. AB - Horses poisoned by a plant may show a myriad of clinical signs. Awareness of the poisonous plants growing in a given area and those that are likely to appear in hay and their associated clinical signs can be instrumental in making diagnoses. More importantly, the information can be shared with clients to help prevent plant poisonings in horses. PMID- 11780286 TI - Mycotoxins. AB - Horses consume feed grains and forages that can produce a range of mycotoxins resulting from mold invasion. Toxicosis of horses often occurs from fumonisins or aflatoxin in grains, from the tremorgenic mycotoxins in dallis grass, or from slaframine in red clover. Fumonisin toxicosis often is severe and fatal, and aflatoxin can be acute or chronic and debilitating. Other mycotoxins reported in horses may cause moderate to mild signs that regress when the contaminated feedstuff is removed. Overall, horses appear to have a relatively low prevalence of reported mycotoxicoses among domestic animals, but they are extremely sensitive to the fumonisins. Since there are no good therapies for mycotoxin poisoning, attention to providing high quality grains and forages to prevent mycotoxicoses is the most effective means for reducing the risk of mycotoxins in horses. PMID- 11780287 TI - Fescue toxicosis. AB - Most of the tall fescue pastures in the United States are infected by an endophyte, N. coenophialum. The fungus derives nutrients from the plant while supplying the plant with toxins for defense. The most detrimental toxins for animals in tall fescue are ergopeptine alkaloids, especially ergovaline. Ergovaline functions as a dopamine D2 agonist and alters prolactin and several other hormones in the body. Pregnant mares are most susceptible during their last month of gestation. Clinical signs include prolonged gestation, dystocia, retained placentas, agalactia, and dysmature foals that are either stillborn or weak. PMID- 11780288 TI - Botulism in the horse. AB - Botulism should be considered in cases where weakness, paralysis, or intolerance to exercise might be seen in the horse. Dysphagia may also be present, although it is not a consistent finding. Potential sources include carrion in hay, moldy or otherwise rotted vegetation or forage, birds carrying material from animal burial or other similar sites, and contaminated carcasses on-site. Horses, especially foals, may also suffer from toxicoinfectious botulism, a condition where the C. botulinum might colonize and produce toxin within the gastrointestinal tract. Wounds also may harbor the organism and otherwise promote botulism. Diagnosis of botulism is often a clinical diagnosis backed up by elimination of other possible infectious, injurious, or toxic causes of weakness of the horse. Definitive diagnosis and type identification in the laboratory are difficult and usually require a suitable sample of the source material. Treatment often is unrewarding unless a case is identified early and the proper antitoxin is readily available. Prevention involves common sense approaches to feeding and care of the horse and, where possible, judicious use of vaccination in endemic areas. PMID- 11780289 TI - Therapeutic flexible bronchoscopy. AB - Since the development of the flexible bronchoscope in late 1960s, its use in the management of various pulmonary disorders, especially lung Ca, has expanded tremendously. It is not only of great diagnostic value, with the recent development of various therapeutic modalities such as Nd:YAG laser, tracheobronchial stents, and cryotherapy, but also its value in management of terminal lung Ca has improved dramatically. Its potential in curing early-stage lung Ca presently is being explored. At present, it is at least partially successful in achieving this goal. More importantly, because of lack of the training in RB and widespread usage of FB, it is more likely that its role in the various interventional procedures, such as Nd:YAG laser therapy, tracheobronchial stent deployment, brachytherapy, and cryotherapy, will grow exponentially. Because of availability of a variety of therapeutic modalities, such as APC, PDT, and balloons, interventional pulmonologists are well equipped to improve the quality of life of terminally ill patients with cancer and maybe to cure early stage lung Ca. PMID- 11780290 TI - Rigid bronchoscopy: the value of a venerable procedure. AB - The rigid bronchoscope is a unique and invaluable instrument that allows evaluation, control, and therapeutic manipulation of the proximal tracheobronchial tree. Massive hemoptysis, foreign body removal, airway stenosis, laser resection, and pediatric bronchoscopy are the most common indications for the rigid bronchoscope. Improved anesthetic agents have improved the safety and comfort of the procedure for patients having either diagnostic or therapeutic procedures. The ability to use the rigid bronchoscope in therapeutic situations depends, however, on a level of skill and experience with the instrument that can be obtained only by its frequent use for diagnostic indications in the proximal airway. PMID- 11780291 TI - Bronchoscopic diagnosis and staging of lung cancer. AB - In the past 2 decades, flexible bronchoscopy (FB) with forceps biopsy and transbronchial needle aspiration (TBNA); computed tomography (CT)-guided, transthoracic fine-needle aspiration (FNA); and endoscopic ultrasonography (EUS) have revolutionized lung cancer diagnosis and staging by facilitating precise biopsy of lung lesions and virtually all mediastinal lymph-node stations. In this article the authors present an algorithm for the diagnosis and staging of lung cancer that addresses sampling of suspicious lesions and lymph nodes by means of FB, CT, ultrasonography, fluoroscopy, and EUS, emphasizing tissue-based diagnosis and staging by means of image-guided technology with the highest diagnostic yield. They discuss the approach to the diagnosis and staging of lung cancer by techniques guided by FB, with particular attention to the increasing role of TBNA in this field. Additionally, the authors propose a rating scale based on the degree of invasiveness and diagnostic yield, comparing FB with other diagnostic techniques. PMID- 11780292 TI - Bronchoscopic diagnosis of infectious and inflammatory pulmonary disease. AB - Use of several bronchoscopic techniques can lead to the rapid and noninvasive diagnosis of many infectious and inflammatory diseases. As these and newer techniques become more widespread, bronchoscopy will continue to be an integral component of the workup of these diseases. PMID- 11780293 TI - Bronchoscopic preparation for airway resection. AB - In patients being considered for tracheobronchial resection and reconstruction, therapeutic bronchoscopy provides a necessary and complementary role to airway resection. Surgeons involved in tracheobronchial reconstruction need to be adept at airway interventions with the flexible and the rigid bronchoscopes. Bronchoscopy is an important part of the evaluation, stabilization, and preparation of the airway before tracheobronchial resection. Therapeutic bronchoscopy also provides the most common alternative to airway resection so that familiarity with the techniques of therapeutic bronchoscopy is important as the surgeon considers the advantages of definitive versus palliative airway management. Furthermore, postoperative complications of tracheobronchial surgery may require therapeutic endoscopic interventions to optimize outcomes after tracheobronchial resection and reconstruction. In patients being considered for airway resection, bronchoscopy provides the most direct assessment for a tissue diagnosis and measurement of the extent of the lesion and its relation to airway landmarks and an assessment of the quality of the airway being considered for anastomosis. Patients who have critical airway stenosis and impending obstruction can be temporized by bronchoscopic dilatation or core out of endoluminal tumor. Bronchoscopic dilatation or core out allows stabilization of the patient, completion of the assessment for surgical resectability, and performance of an elective rather than an emergent surgical resection. By relieving airway obstruction, therapeutic bronchoscopy also can improve the assessment of tumor margins and allow for clearing of an obstructive pneumonia so that postoperative pulmonary and anastomotic complications are minimized. Airway resection remains the preferred definitive approach for benign and malignant airway pathologies, but therapeutic bronchoscopy provides a useful adjunct to surgery in assessing the patient for surgical resection, preparing the patient for surgery, and optimizing postoperative results. PMID- 11780294 TI - Bronchoscopic management of benign stenosis. AB - In summary, the use of laser technology in the airway for the treatment of benign lesions has become a standard therapeutic modality for the airway endoscopist. It is extremely important that endoscopists be well acquainted with the laser soft tissue interactions of the laser being used and the safety precautions associated with each individual wavelength. They should be conversant with the indications and contraindications and have the ability to use adjuvant therapeutic modalities, such as stents and medications. As usual, patient selection is one of the key factors related to successful management. PMID- 11780295 TI - Laser bronchoscopy. AB - Because the lung cancer epidemic shows no signs of abating, little doubt exists that the need for interventional bronchoscopists will persist for many years to come. The Nd:YAG laser and the rigid bronchoscope remain crucial weapons in the fight against lung cancer. With more than 4000 published interventions pertaining to it, this combination is ideal for treating central airways obstruction. The safety and efficacy of laser bronchoscopy has been well established, and the reported incidence of complications is impressively low. If complications were to arise, a skilled bronchoscopist can manage them easily by using the beneficial attributes of the rigid bronchoscope. Many complications can be avoided by implementing the established safety procedures and techniques. A solid understanding of laser physics and tissue interactions is a necessity to anyone performing laser surgery. The team approach, relying on communication among the bronchoscopist, anesthesiologist, laser technician, and nurses, leads to a safer and more successful procedure. It is important to remember, however, that this is typically a palliative procedure, and therefore the focus should be on alleviating symptoms and improving quality of life. Unfortunately, because not every patient is a candidate for laser bronchoscopy, there are specific characteristics of endobronchial lesions that make them more or less amenable to resection. Each year a promising new technology is being developed, such as argon plasma coagulation, cryotherapy, and endobronchial electrosurgery. Although it is unclear what role these technologies will have, prospective controlled studies must be done to help clarify this question. The future may lay in combining these various technologies along with Nd:YAG laser bronchoscopy to maximize the therapeutic, palliative, and possibly even curative effect. As the experience of the medical community with Nd:YAG laser bronchoscopy continues to grow and as more health-care professionals are made aware of its therapeutic capability, fewer patients with cancer will need to suffer and die from the complications of airway obstruction. PMID- 11780296 TI - Endobronchial cryosurgery. AB - The use of cryosurgery in the tracheobronchial region has been established for a considerable time, and it has been proved to provide a safe, rapid, and effective method for the restoration of patency in blocked tracheobronchial lumen. It also improves symptoms, respiratory function, and quality of life. The technique is easy to perform, economical, has minimal complications, and is well tolerated by the patient. Cryosurgery often leads to sufficient improvement in the patients' condition such that they can tolerate further treatments, such as radiotherapy or chemotherapy, thus providing a better outcome and improved quality of life and survival. PMID- 11780297 TI - Endobronchial brachytherapy. AB - High-dose rate endobronchial brachytherapy is a well-tolerated out-patient procedure that provides a high likelihood for durable palliation of symptoms associated with endobronchial tumor. The most significant associated toxicity is late massive hemoptysis, the risk for which can be minimized by careful treatment planning and limiting the size of the delivered dose per fraction to less than 10 Gy, prescribed at 1 cm distance. PMID- 11780298 TI - Endobronchial photodynamic therapy for the treatment of lung cancer. AB - After 2 decades of basic research and clinical experience with endobronchial photodynamic therapy, clear indications for its use have arisen. PDT for the treatment of superficial NSCLC is a viable alternative for patients with inoperable lung cancer. Although early indications are that it may be used to spare operable patients an aggressive surgical procedure, this application still should be considered investigational. The standard of care remains surgical resection in the operable patient. PDT may be considered for the palliation of obstructing lesions of the tracheobronchial tree; however, the risk for prolonged sensitivity to sunlight limits its broad application in this patient population. As better screening techniques are introduced, the role of PDT will expand in the future management of superficial lung cancers. Future developments include new photosensitizers with decreased duration of sun sensitivity and greater choice of wavelength to affect depth of penetration, better dosimetry systems for more consistent light delivery and reporting of results, and better light delivery systems for more homogenous distribution of light. PMID- 11780299 TI - Airway stenting. AB - Various airway pathologies may result in central airway obstruction. For patients who have benign and malignant disease, definitive surgical correction by tracheobronchial resection and reconstruction is preferred. Numerous patients, however, have unresectable airway lesions owing to the extent of disease or to medical or surgical contraindications. These patients can be palliated by several endoscopic strategies, including dilatation, core out of tumor, laser resection, endobronchial brachytherapy, or photodynamic therapy. Airway stenting with silicone or expandable metal stents provides reliable and durable palliation in 80% to 95% of properly selected patients. The major advantages of silicone stents are the ease of customization, repositioning, and removal, with the major drawbacks being stent migration or stent obstruction. Expandable metal stents have the advantage of ease of insertion, conformation to the airway, low inner-to outer diameter ratio, and stent stability. These advantages, however, are offset by (1) the development of tumor ingrowth or of granulation at the end of the stent or through the interstices of the stent and (2) the difficulty or impossibility of stent repositioning or removal once it has been seated completely within the airway. Management of the patient who has central airway obstruction requires a thorough knowledge and consideration of the surgical and endoscopic management options and, usually, a multidisciplinary approach, with experienced thoracic surgical consultation to evaluate the potential for definitive surgical correction. The interventional bronchoscopist must consider the spectrum of endoscopic therapeutics fully. Most patients benefit from combining strategies in a flexible algorithm directed at optimizing patient outcomes. The benefits and risks of airway stenting must be considered in comparison with the other options for airway palliation. In refractory strictures, rapidly recurrent tumor, or extrinsic compression, endobronchial stenting likely will be necessary to achieve durable palliation of airway obstruction. The short- and long-term implications of airway stenting, including the complications of silicone versus expandable metal stents, should be considered thoroughly, while the physician bases treatment or procedure decisions on individual patient anatomy and expected natural history. PMID- 11780300 TI - Tracheobronchial foreign bodies. AB - Aspiration of tracheobronchial foreign bodies occurs more commonly in children, but under certain circumstances, it also can occur in adults. The most common symptoms are choking followed by a protracted cough. Physical examination findings include fever, stridor, retractions, and decreased breath sounds. Radiographic imaging can be helpful if the object aspirated is radiopaque or if there are signs of hyperexpansion on expiration. Negative-imaging studies, however, do not exclude the presence of a foreign body in the airway. The longer a foreign body resides in the airway, the more likely it is to migrate distally. When this occurs, symptoms of chronic cough and wheezing may mimic an asthmalike condition. Bronchoscopy is indicated in this situation to evaluate the airway thoroughly. If a foreign body is present, extraction can be performed with flexible or rigid bronchoscopy. If flexible bronchoscopy is attempted, it is imperative that the bronchoscopist is familiar with rigid bronchoscopy and has the equipment immediately available should danger to the airway occur. The procedure is generally safe and well tolerated. Many patients are managed under general anesthesia, but foreign bodies often can be removed with a flexible bronchoscope with the patient under local anesthesia. Surgery should be performed only as a last resort and rarely is necessary. PMID- 11780301 TI - Role of bronchoscopy in massive hemoptysis. AB - Airway hemorrhage is a potentially rapidly fatal condition. Death may occur within minutes from asphyxiation before control can be achieved. The primary prognostic factors are the rate of bleeding and the underlying cardiopulmonary status of the patient. Bronchoscopy is central in management, but the goals differ, depending on circumstances. In stable patients who have minimal hemoptysis, bronchoscopy can diagnose the cause specifically and be used as the primary treatment modality. In the setting of massive or life-threatening bleeding, bronchoscopy primarily is performed to maintain ventilation and to direct endobronchial blockade. Although flexible bronchoscopy is an acceptable mode initially, there should be no delay in performing rigid bronchoscopy when it becomes apparent that bleeding is too vigorous to permit [figure: see text] successful airway exploration with the smaller flexible instrument. Once isolation of bleeding has been achieved, the choice must be made between embolization, surgical resection, or both of these procedures. PMID- 11780302 TI - Endoscopic management of airway complications after lung transplantation. AB - Airway complications remain a source of significant morbidity after lung transplantation. The current incidence of such complications is 12% to 15%. The associated mortality is 2% to 3%. Extensive necrosis and anastomotic dehiscence have become rare, but granulation tissue accumulation, stenosis, and bronchomalacia persist. The major factors that increase the risk for such complications are those that aggravate anastomotic ischemia. Because blood flow to the donor main-stem bronchus is derived from collateral circulation from the pulmonary arteries, minimizing pulmonary inflammation, optimizing pulmonary blood flow, and limiting exposure to positive pressure ventilation are important considerations. Attention to organ preservation techniques and perioperative management is critically important. Controversy remains regarding the optimal anastomotic technique, but properly done, end-to-end anastomosis is readily reproducible and is associated with a low incidence of complications. Attempts to restore the bronchial circulation surgically are not associated with significant reductions in airway complications. Similarly, the routine use of vascularized soft tissue reinforcement no longer seems justified. Most complications can be managed readily with a combination of endoscopic techniques, including debridement (with or without laser or cryotherapy), dilation, and stent placement. Resective procedures rarely are indicated, and retransplantation should be reserved for exceptional cases. PMID- 11780304 TI - Miller Fisher syndrome: toward a more comprehensive understanding. AB - PURPOSE: To review recent knowledge on the clinical features, pathology and pathophysiology, diagnosis and treatment of Miller Fisher syndrome (MFS). DATA SOURCES: Clinical and laboratory studies on MFS in the past 10 years were included. RESULTS: A viral infection preceded neurological symptoms in 71.8% of MFS patients. Typical MFS consists of the triad of ataxia, areflexia and ophthalmoplegia. Other cranial nerves are also involved, which may overlap with limb weakness in typical Guillain-Barre syndrome (GBS). Lower cranial nerve variants of GBS, atypical MFS and ataxic neuropathies may overlap, and are thought of as variant forms of MFS. Recurrence and CNS involvement is found more frequently in MFS than in GBS. Antibody to GQ1b, a tetrasyaloganglioside (GQ1b antibody) which is found in close relation to ophthalmoplegia in MFS, is also associated with Campylobacter jejuni (C. jejuni) serotype Penner 2. This suggests that C. jejuni may induce MFS via the GQ1b structure. The GQ1b antibody may lead to the failure of acetylcholine release from motor nerve terminals, which has been confirmed by clinical neurophysiological results. CONCLUSIONS: Many studies have shown similarities in the pathogenesis of MFS and GBS. However, there are still some differences between them, especially in the areas of sensory and CNS involvement. The GQ1b antibody is thought of as one of the key factors in the pathogenesis of MFS, especially with ophthalmoplegia, and it may prove a useful clinical marker in the diagnosis of MFS. PMID- 11780303 TI - Parkinson's disease therapy: treatment of early and late disease. AB - PURPOSE: To summarize the current strategies for the treatment of early and late Parkinson's disease (PD). DATA SOURCES: The presented guidelines are based on the review of the literature as well as the author's extensive experience with the treatment of 7000 patients with PD over the past 25 years. RESULTS: An analysis of reported data as well as personal experience suggest that while young patients seem to have a slower progression of the disease, they are at a higher risk for developing levodopa induced complications, such as motor fluctuations and dyskinesias. It is, therefore, prudent practice to delay levodopa therapy, particularly in younger patients, until the PD symptoms become troublesome and interfere with social or occupational functioning. Other strategies, such as the use of deprenyl, amantadine, trihexphenidyl and dopamine agonists, should be employed before instituting levodopa therapy. Entacopone and dopamine agonists are useful in smoothing out levodopa related motor fluctuations. Surgical interventions, such as pallidotomy and pallidal or subthalamic deep brain stimulation, are effective therapeutic strategies, but should be reserved only for patients in whom optimal medical therapy fails to provide satisfactory control of symptoms. CONCLUSION: The medical and surgical treatment of patients with PD must be individualized and tailored to the needs of the individual patient. PMID- 11780305 TI - Eldepryl prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral neuronal apoptosis in mice. AB - OBJECTIVE: To study the apoptotic effects of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1-methyl 4-phenylpyridium ion (MPP+) on pheochromocytoma (PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect. METHODS: Three groups of C57BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase-mediated dUTP-x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra. The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP+, MPTP or PBS. RESULTS: Intraperitoneal administration of MPTP 30 mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP. MPP+, an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells. CONCLUSIONS: The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP+. Eldepryl could protect the neurotoxicity from MPTP. PMID- 11780306 TI - Effects of free radicals and amyloid beta protein on the currents of expressed rat receptors in Xenopus oocytes. AB - OBJECTIVE: To investigate the effects of free radicals (FRs) and amyloid beta protein 1-40 (A beta 1-40) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes. METHODS: Total RNA and messenger RNA (mRNA) was prepared from 3-month-old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes (stages V-VI) with 50 nl (50 ng) for each oocyte. The microinjected oocytes were incubated with modified Bath's solution at 19.0 degrees C +/- 1.0 degree C for receptor expression and their currents were recorded with double electrode voltage clamp technique. Superoxide anion free radicals (SAFRs) were produced via a reaction system (HPX/XO) with hypoxanthine (HPX, 0.05 mol/L) and xanthine oxidase (XO, 0.1 U/L). In order to observe the effects of A beta and SAFRs on the expressed glutamate receptor, HPX/XO and A beta 1-40 were added to incubation solution at 12 h, 24 h and 96 h before recording. RESULTS: The results showed that the oocytes expressed functional NRs originating from rat brain tissues. These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin (5-HT) and gamma aminobutyric acid (GABA). The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to -22 mV. The extent of effect on the current of expressed glutamate receptor from rat brain was different among different A beta concentrations and incubation times. A beta 1-40 at a concentration of 20 nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24 h of incubation period; but the currents of glutamate receptor were significantly decreased (25% off, P < 0.01) in the treatment of 60 nmol/L A beta 1-40 over 24 h. Moreover, when 20 nmol/L A beta 1-40 was co-incubated over 12 h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly. When the oocytes were co-treated with 60 nmol/L A beta 1-40 and SAFRs over a period of 12 h, the currents of glutamate receptor significantly decreased (21% off, P < 0.05), and the decreased percentage reached 52% over 24 h co-treatment with 60 nmol/L A beta 1-40 and SAFRs. In addition, vitamin E had a partial effect against this inhibitory effect. CONCLUSION: The results suggest that A beta has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals. The effects can be antagonized by vitamin E. These imply that A beta may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease. PMID- 11780307 TI - Neuronal cdc-2 like kinase in developing kindling rat hippocampus. AB - OBJECTIVE: To test the hypothesis that neuronal cdc2-like kinase (Cdk5/p35nck5a) plays an important role in neuronal maturation and sprouting. METHODS: Changes kinase activity, expression levels and subcellular localizations of Cdk5 and p35nck5a in the rat hippocampus were studied during kindling progression by Western blot analysis, immunohistochemistry, immunoprecipitation and kinase assay. RESULTS: Kinase activity in kindling rats was significantly higher than that in normal adult rats. The kinase activity at stage 3 was most prominent among all stages of kindling progression. The changes in kinase activity coincided with those of p35nck5a expression in kindling rats. In contrast, the expression of Cdk5 was constant throughout the progression of kindling stages. However, subcellular localization of Cdk5 dramatically changed in the hippocampal neurons of kindling rats. Cdk5 was translocated from axon to soma when kinase activity was high. p35nck5a was always localized in the soma throughout kindling progression. CONCLUSIONS: Neuronal cdc2-like kinase plays an important role in synaptic reorganization, and the translocation of Cdk5 to the soma from the axon may be a novel regulatory mechanism to control kinase activity. PMID- 11780308 TI - Modulation of BmKAS-1 and BmK1-3-2 to sodium channel in rat dorsal root ganglion neurons. AB - OBJECTIVE: To investigate what effects BmKAS-1 (a polypeptide purified from the Chinese scorpion Buthus martensi Karsch [BmK] and named as BmK activator of skeletal-muscle ryanodine receptor) and its upstream mixture BmK1-3-2 have on Na+ channels in dorsal root ganglion (DRG) small diameter neurons. METHODS: The whole cell patch-clamp technique was used to investigate the effects of BmKAS-1 and BmK1-3-2 on Na+ current in rat small diameter DRG neurons. RESULTS: About 50% peak Na+ current was suppressed by 10 micrograms/ml of BmK1-3-2. 1.62 micrograms/ml of BmKAS-1 also blocked 50% peak Na+ current, and there was an obvious dose-dependent relationship. CONCLUSION: Both BmK1-3-2 and BmKAS-1 have a blocking effect on Na+ channels, and this may one of the mechanisms for the analgetic effect of BmK1-3-2 and BmKAS-1. PMID- 11780309 TI - Monitoring of antegrade selective cerebral perfusion for aortic arch surgery with transcranial Doppler ultrasonography and near-infrared spectroscopy. AB - OBJECTIVE: To evaluate the safety and efficacy of antegrade selective cerebral perfusion (ASCP) during aortic arch surgery as a means of extending the safe period of systemic circulatory arrest using multimodality neuromonitoring to objectively quantify the physiologic responses. METHODS: In twenty-two patients (all less than age 60) scheduled for repair of an aortic arch aneurysm, preoperative verification of effective collateral perfusion through both the carotid and vertebrobasilar arterial systems was documented with transcranial Doppler ultrasonography (TCD). During cardiopulmonary bypass, the sole arterial inflow from the pump was via the right subclavian artery. The magnitude of ASCP was quantified by TCD using peak middle cerebral artery velocity, while flow adequacy was measured by continuous regional cerebrovenous oxygen saturation (rSO2) using dual-wavelength spatially resolved near-infrared spectroscopy. RESULTS: All patients experienced an uneventful recovery. Flow in the middle cerebral artery became undetectable at ASCP < 5 ml.kg-1.min-1, so adjustments from a 15-20 ml.kg-1.min-1 baseline were used to maintain rSO2 above 50%. Furthermore, ASCP flow was highly correlated (P < 0.01) with both peak middle cerebral artery velocity and rSO2(r = 0.86 and 0.96, respectively). CONCLUSION: Neuromonitoring guided ASCP may be expected to extend the safe period and is at least partly responsible for the absence of neurologic complications in this patient cohort. PMID- 11780310 TI - Intracoronary stent implantation under intracoronary ultrasound guidance with aspirin and ticlopidine therapy. AB - OBJECTIVE: To observe the immediate angiographic and intravascular ultrasound (IVUS) results and their effects on one month clinical outcomes in forty-one patients who submitted to coronary stent deployment with IVUS guidance. METHODS: All patients were allocated to coronary stent implantation with high inflation pressure. After good angiographic results (< 20% residual stenosis), all patients underwent IVUS and higher-pressure dilatation would be necessary if criteria for optimal coronary stent implantation were not met. The optimal criterion of IVUS for stent implantation was the ratio of intrastent lumen cross-sectional area to the average of the proximal and distal reference lumen cross-sectional areas > or = 80%. All patients had aspirin and ticlopidine therapy on the day of angioplasty and during the one month follow-up period. RESULTS: Optimal criteria of IVUS were obtained without any further intrastent dilatation in twenty-five patients but intrastent higher-pressure dilatation was performed in fourteen patients whose ultrasound results did not reach the criteria. In these patients, we increased the minimal intrastent lumen area 25.7% (P < 0.05). Thirty-five patients (90%) had good minimal intrastent lumen area of IVUS. There were no deaths, myocardial infarction, acute stent thrombosis or need for revascularization during the study and the one month follow-up. CONCLUSIONS: Intracoronary stent deployment under IVUS guidance, including combining aspirin and ticlopidine therapy, had beneficial ultrasound results and good clinical outcomes after one month follow up. PMID- 11780311 TI - Relationship between gene polymorphism of the PAI-1 promoter and myocardial infarction. AB - OBJECTIVE: To investigate the association between gene polymorphism of the plasminogen activator inhibitor-1 (PAI-1) and myocardial infarction (MI) in Chinese. METHODS: PAI-1 genotyping with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific polymerase chain reaction (ASPCR) was performed in 87 myocardial infarction patients and 92 unrelated healthy controls. All subjects' clinical features and PAI-1 activity were tested. RESULTS: There were two polymorphisms within the promoter, a G/A single base substitution polymorphism upstream at -844 bp, and a single guanosine deletion/insertion 4G/5G polymorphism -675 bp upstream from the start of transcription. Significant differences between the patients and the controls were observed neither for the frequencies of the GG, GA and AA genotypes nor for the PAI-1 activities of these three types. But for the 4G/5G polymorphism, there were significant differences between patients and controls for the frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes (P < 0.05). In the MI group, the PAI-1 activity of the 4G/4G type was significantly higher than that of the 5G/5G type (P < 0.05). Further more, a positive correlation between the glucose level and PAI-1 activity was found (r = 0.34, P = 0.02). CONCLUSION: This study indicates that the 4G/5G gene polymorphism of PAI-1 is associated with myocardial infarction, that 4G/4G type is probably an important hereditary risk factor, and that glucose has functional importance in regulating PAI-1 activity. PMID- 11780312 TI - Antihypertension and anti-cardiovascular remodeling by phenylalanine in spontaneously hypertensive rats: effectiveness and mechanisms. AB - OBJECTIVE: To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). METHODS: The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3H-thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca2+ influx was measured in counts/min of 45CaCl2 after incubating it with 5 different concentrations of phenylalanine and the intracellular [Ca2+]i by Fura-II/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen alpha 2 (I) cDNA. The tyrosine hydroxylase (TH) activity was measured by high-performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of pharmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3H-L-phe (1 ml/kg) by PK-GRAPH Program for kinetic calculation. The 3H-L-phe uptake by CSMCs after incubating for definite intervals was also detected and compared. RESULTS: Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearranged cardiovascular structure was much improved. The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhibition of collagen alpha 2(I) cDNA, c-fos and c-myc expression. Other mechanisms may include decrease of intracellular [Ca2+]i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus. Besides, partial recovery of phenylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness. CONCLUSIONS: Phenylalanine intervention could exert a definite anti-hypertension and anti-cardiovascular remodeling effects on SHRs like seen in human essential hypertension. Its mechanisms might be related to direct inhibition of growth in the cardiovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellular [Ca2+]i. PMID- 11780313 TI - The relationship between plasma apolipoprotein A-IV levels and coronary heart disease. AB - OBJECTIVE: To evaluate the relationship between plasma apoA-IV levels and coronary atherosclerosis and to explore its relation to other risk factors. METHODS: Using ELISA techniques, plasma apoA-IV levels were quantified in 181 patients who underwent coronary angiography (CAG). Patients were divided according to their coronary status into a coronary heart disease (CHD) group (stenotic lesion on CAG, n = 118) and a control group (normal CAG, n = 63). The severity of atherosclerosis was assessed by stenosis scoring of the different lesions. Other parameters, including apoA-I, apoB, Lp(a), HDL-C, LDL-C, TG, and TC, were measured as well. Univariate, logistic regression analyses were used to define the relationship between coronary atherosclerosis and plasma apoA-IV levels. RESULTS: When compared with the control group, plasma apoA-IV levels were found to be lower in the CHD group. There was a weak negative correlation between plasma apoA-IV levels and the severity of coronary atherosclerosis. ApoA-IV was found to be a relatively independent risk factor for CHD. We also found a positive correlation between apoA-IV and triglyceride levels. CONCLUSIONS: ApoA IV may be important in the prediction of CHD and coronary atherosclerosis severity. It may also play an important role in the metabolism of triglycerides. PMID- 11780314 TI - Hepatic angiomyolipoma: a clinicopathologic study of 10 cases. AB - OBJECTIVE: To study the clinicopathologic features of hepatic angiomyolipoma (AML) and to investigate the feasibility of a new antibody-A103 as a diagnostic aid for AML. METHODS: Ten cases of AML were retrieved from hospital records and analyzed morphologically. Immunohistochemistry was performed on paraffin-embedded tissues with a panel of antibodies, including antibody-A103. RESULTS: There were eight women and two men, with ages ranging from 38-58 years (median 45.7). Clinically, nine cases were asymptomatic and found by imaging techniques. None of the patients had associated tuberous sclerosis. All tumors were sharply demarcated from the surrounding liver parenchyma. Histologically they were composed of a heterogeneous mixture of three components: thick-walled blood vessels, spindle or epithelioid smooth muscle cells and adipose tissue. All tumors showed a strong immunoreactivity to A103, HMB-45 and smooth muscle actins. Follow-up information on all 10 cases showed a benign course with no signs of recurrence. CONCLUSIONS: Hepatic AML is a rare mesenchymal tumor of the liver. A103 is a promising marker for a pathologic diagnosis of hepatic AML. PMID- 11780315 TI - Analysis of hypermutation of the 5' noncoding region in the BCL-6 gene. AB - OBJECTIVE: To investigate BCL-6 gene mutations in Chinese populations with B-cell non-Hodgkin's lymphoma. METHODS: Polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing were used to identify mutations in the 5' noncoding region of the BCL-6 gene in a total of 40 cases of diffuse large-cell lymphoma (DLCL) and follicular lymphoma (FL). RESULTS: Nine cases were found to have base substitutions. The incidence of BCL-6 gene mutation and the frequency of single-base changes were approximately 25.7% and (0.56-1.10) x 10(-2)/bp, respectively. CONCLUSIONS: The 5' regulatory region of the BCL-6 gene undergoes frequent somatic hypermutation during lymphomagenesis and the identification of BCL-6 gene hypermutations provides a molecular marker for confirmatory diagnosis of B-NHL. PMID- 11780317 TI - Epidemiological study of pathogenic fungi in China: 1986 and 1996. AB - OBJECTIVE: An annual decade epidemiological survey of pathogenic fungi of inpatients or outpatients includes more than 25 provinces in China has been done in 1986 and 1996. METHODS: In 1986, there were a total of 9096 strains of pathogenic fungi collected from more than 41 units of 25 provinces in China. 10 years late, 18,085 strains of pathogenic fungi from 41 units of 25 provinces were collected from January 1st to December 31st in 1996. RESULTS: The results showed that during this decade the prominent pathogenic fungus was Trichophyton rubrum, but its ratio gradually decreased. On the contrary, Candida albicans gradually increased in its ratio from 5th in 1986 to 2nd in 1996. CONCLUSION: The pathogenic fungi in China have changed greatly in the past decade from 1986 to 1996. PMID- 11780316 TI - Effects of sex hormones on apoptosis in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. AB - OBJECTIVE: To study the effects of dehydroepiandrosterone (DHEA) and/or estradiol (E2) on apoptosis in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: The percentage of apoptosis of PBMCs from SLE patients and healthy blood donors were examined by means of AO staining 48 h after culture with DHEA and/or E2 at physiologic or pathologic concentrations. RESULTS: The percentage apoptosis of PBMCs from SLE patients is higher than that of healthy blood donors (P < 0.01). E2, whether at physiological or at pathological concentrations, had no effects no apoptosis of PBMCs from both SLE patients and healthy donors (P > 0.05). Both DHEA and DHEA plus E2 at physiologic concentrations, had no effect on apoptosis of PBMCs from healthy donors (P > 0.05), but significantly inhibited that of SLE patients (P < 0.05); at pathologic concentrations, they promoted apoptosis of PBMCs from SLE patients as well as healthy blood donors (P < 0.05). There were no significant differences between the effects of DHEA and that of DHEA plus E2 (P > 0.05). CONCLUSION: DHEA plays an important role in the apoptosis of PBMCs from SLE patients; low serum levels of DHEA may cause accelerated apoptosis. PMID- 11780318 TI - Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation. AB - OBJECTIVE: To further reveal serious risks of heroin abuse to human body and clarify grave injuries of oxidation, peroxidation and lipoperoxidation induced by nitric oxide and other free radicals to heroin abusers. METHODS: Determined and compared plasma levels of nitric oxide (P-NO), vitamin C (P-VC), vitamin E (P VE), beta-carotene (P-beta-CAR), lipoperoxides (P-LPO) and erythrocyte activities of superoxide dismutase (E-SOD), catalase (E-CAT), glutathione peroxidase (E-GSH Px) and erythrocyte level of lipoperoxides (E-LPO) in 137 cases of heroin abusers (HAs) and 100 cases of healthy volunteers (HVs), used linear regression and correlation, stepwise regression and correlation to analyze correlation among heroin-abusing-duration (HAD), daily-heroin-abusing-quantity (DHAQ) with above determination values in the HAs. RESULTS: Compared with the above average values in the HVs group, the average values of P-NO, P-LPO, E-LPO in the HAs group were significantly increased (P < 0.0001), the average values of P-VC, P-VE, P-beta CAR, E-SOD, E-CAT and E-GSH-Px were significantly decreased (P < 0.0001); the analysis of linear regression and correlation showed that with ascending of the HAD and DHAQ in the HAs, the values of P-NO, P-LPO, E-LPO were gradually increased (P < 0.0001), the values of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT, E-GSH Px were gradually decreased (P < 0.0001); the analysis of stepwise regression and correlation suggested that the correlation among the HAD, DHAQ with the values of P-NO, P-VC, P-VE was the closest. CONCLUSION: The balance between oxidation and antioxidation in the HAs was seriously destroyed, and the injuries induced by nitric oxide and other free radicals, oxidation, peroxidation and lipoperoxidation reactions to the body of HAs gravely exacerbated. In the abstaining from heroin dependence, therefore, it should consider that sufficient quantum antioxidants such as VC, VE and beta-CAR are dosed to the HAs so as to abate the injuries to their bodies. PMID- 11780319 TI - Growth inhibition of interleukin-2 receptor gene-transduced peripheral blood lymphocytes on human ovarian cancer cells. AB - OBJECTIVE: To investigate the growth inhibition of interleukin-2 receptor (IL-2R) gene-transduced peripheral blood lymphocytes (PBLs) on human ovarian cancer cells. METHODS: Interleukin-2 (IL-2) and IL-2R genes were transfected into human ovarian cancer cell line 3AO and PBLs, respectively, using the same Fugene vector. Twenty-four hours later transfected and nontransfected PBLs were cocultured with transfected and nontransfected 3AO for 48 hours. cytotoxicity of PBLs on 3AO was detected by the MTT assay. RESULTS: The morphology of IL-2 transduced 3AO and IL-2R-transduced PBLs remained unchanged. 3AO cells could be transfected with the IL-2 gene and expressed IL-2 mRNA, and PBLs could be transfected with the IL-2R gene and expressed IL-2R mRNA. IL-2 transduced 3AO cells enhanced their response to the cytotoxicity of PBLs. Furthermore, growth inhibition of PBLs to 3AO cells increased significantly when the IL-2R was transfected into PBLs and when the IL-2 gene was transfected into 3AO cells and the two were combined. CONCLUSIONS: IL-2R gene transduced PBLs are able to enhance their cytotoxicity on IL-2 gene transduced ovarian cancer cells. This method may be a new way to investigate IL-2 gene therapy for ovarian cancer. PMID- 11780320 TI - The relationship between cartilage end-plate calcification and disc degeneration: an experimental study. AB - OBJECTIVE: To study the relationship between cartilage end-plate calcification and intervertebral disc degeneration. METHODS: An experimental model of cervical disc degeneration in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from the cervical vertebrae. Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration. The extent of intervertebral disc degeneration was graded in morphologically, and the thicknesses of the calcified layer and the uncalcified layer of the cartilage end-plate were measured in each degenerated cervical disc. RESULTS: In less severely degenerative cervical discs, the morphology of the cartilage end-plate showed nearly normal construction, and the tidemark was clear. In severely degenerative discs, the matrix and cells showed fibrosis, the tidemark advanced, and the calcified cartilage thickened. There exists a positive correlation between the thickness of the calcified layer of the cartilage end-plate and the degree of cervical disc degeneration. CONCLUSION: The calcification of the cartilage end-plate is the key factor that initiates and promotes cervical disc degeneration. PMID- 11780321 TI - Sodium channels in the apical membrane of human nasal epithelial cells. AB - OBJECTIVE: To study the electrophysiological properties of sodium channels in the apical membrane of human nasal epithelial cells. METHOD: Nasal epithelial cells of human inferior turbinate from patients with obstructive sleep apnea syndrome were cultured in serum free medium on collagen gel-coated membranes at an air liquid interface and studied by a patch clamp technique. RESULTS: In cell attached patches, a typical single channel current with a conductance of 21.09 pS and reversal potential of -50.96 were recorded. The permeability ratio PNa/PK was more than 5.80. In the presence of 10(-4) mmol/L amiloride in the pipette, the incidence of sodium channels decreased from 26.67% to 5.13%. This revealed that a population of channels were inhibited by amiloride at a dose of 10(-4) mmol/L. Ca2+ at dose of 10(-3) mmol/L did not influence the incidence of sodium channels. There was no obvious association between voltage and the open probability of the channels. CONCLUSIONS: Our results indicate that most Na+ channels in cell attached patches of human nasal epithelial cells are amiloride-sensitive and Na+ selective. Only a few channels are amiloride-insensitive. The channels were not activated by extracellular Ca2+ and the open probability followed a voltage independent manner. PMID- 11780322 TI - Immunity induced by DNA vaccine of plasmid encoding the rhoptry protein 1 gene combined with the genetic adjuvant of pcIFN-gamma against Toxoplasma gondii in mice. AB - OBJECTIVE: To construct the eukaryotic expression recombinant plasmid, pcIFN gamma, as a genetic adjuvant and observe the immune responses elicited by pcDNA3 rhoptry protein 1 (pc-ROP1) combined with pcIFN-gamma against Toxoplasma gondii (T. gondii) infection in mice. METHODS: A fragment of the IFN-gamma gene was directly inserted into the pcDNA3 plasmid and identified by two restriction endonucleases digestion. pcIFN and pcROP1 DNA was injected into the left leg muscle of mice at a dosage of 100 micrograms, and a booster vaccination was given at the same dosage after two weeks. Control groups were injected with pcDNA3 blank plasmid or normal saline. At 30, 50 and 70 days after booster injection, kinetic tests were carried out: MTT assay for the proliferation response of T lymphocyte cells and the activity of NK cells, sandwich ABC-ELISA for the determination of IFN-gamma, IL-2 and IL-10; a serum enzymetic aassay for nitric oxide (NO) in sera and ELISA for the titer of IgG antibody in sera. RESULTS: The recombinant plasmid, pcIFN-gamma was constructed. The proliferation response of spleen T lymph cells, NK cell killing activity, and serum levels of IFN-gamma, IL 2 and NO in mice injected with pcROP1 and pcIFN-gamma were higher than in those injected with pcROP1 alone. There was no difference in IgG antibody levels between the two groups. CONCLUSION: The genetic adjuvant, pcIFN-gamma, could enhance the cellular immune response induced by DNA vaccine of pcROP1 in mice against Toxoplasma gondii infection. PMID- 11780323 TI - Increased activity of protein kinase C in alveolar macrophages in idiopathic pulmonary fibrosis. AB - OBJECTIVE: To investigate the changes on protein kinase C (PKC) activity of alveolar macrophages (AMs) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: The PKC activity of AM in 9 healthy volunteers and 15 patients with IPF was investigated by measuring the radioactivity. RESULTS: The total, cytosolic and membrane PKC activity of AM in bronchoalveolar lavage fluid (BALF) from patients with IPF were higher than those from control group (P < 0.01, P < 0.05 and P < 0.05, respectively). The total and the membrane-associated PKC activity had a positive correlation with the number of cells in BALF (r = 0.8135, P < 0.01 and r = 0.5917, P < 0.05), respectively. CONCLUSION: As a bypass of transmembrane signal transduction, PKC was suggested to be involved in the origination and development of IPF. PMID- 11780324 TI - Pseudo-cerebrospinal fluid rhinorrhea following traumatic cerebrospinal fluid rhinorrhea surgery: a case report. PMID- 11780325 TI - Chimera formation of platelet GP II b Bak a/b by intrauterine transplantation of fetal liver stem cells. AB - OBJECTIVE: To investigate whether artificial heterozygous chimeras of platelets can be established by intrauterine transplantation of fetal liver stem cells and evaluate its potential use for the treatment of Glanzmann thrombasthenia. METHODS: Platelet glycoprotein (GP) II b Bak a/b (or GP II b I le843Ser) was used as a genetic marker. A homozygous 16-week-old Bak a/a fetus (as donor) and a homozygous 16.5-week-old Bak b/b fetus (as recipient) were screened from 42 pregnant women hospitalized for abortion. PCR with allele specific primers and FOK I digestion based on PCR products were used. Aborted donor fetal liver cell suspensions were prepared and intrauterine transplantation was carried out by infusion of 4 ml fetal liver cells (22 x 10(5)) into the recipient umbilical vein under ultrasonic visualization. RESULTS: At gestation termination (abortion), 21 days after transplantation, chimera GP II b Bak a/b of the recipient were detected by FOK 1 digestion based on PCR from DNA and RT-PCR from platelet RNA. CONCLUSION: Intrauterine transplantation of fetal liver cell may provide an effective way for curing GT or other inherited diseases. PMID- 11780326 TI - Human stem cell model to study signal transduction and molecular regulation mechanisms in CML. AB - OBJECTIVE: To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. METHODS: We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. RESULTS: We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. CONCLUSION: This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells. PMID- 11780327 TI - Protective effect of human CD40-Ig fusion protein in a murine model of acute graft-versus-host disease. AB - OBJECTIVE: To investigate the protective effects of blocking CD40/CD40L interactions with human CD40-Ig fusion protein in a murine graft-versus-host disease model. METHODS: Human CD40 gene extracellular region was inserted into plasmid pIG1, which contains genomic human IgG1 Fc gene. A transient vector containing CD40-Fc fusion gene was transfected into COS-7 cells. The CD40-Ig fusion protein was detected through enzyme-linked immunosorbent assay (ELISA). A constitutive vector was also generated by ligating the CD40-Fc fusion gene into pcDNA3.1 and transfecting it into CHO cells. CD40-Ig was purified by protein A affinity chromatography. SDS-PAGE, Western blot and ligand binding assay were used to identify the qualities of CD40-Ig. Murine acute graft-versus-host disease (GVHD) was induced by intravenous injection of C57BL/6J (H-2b) spleen cells into sub-lethally irradiated BALB/c (H-2d) mice. Protective effects against murine graft-versus-host disease by in vivo administration of CD40-Ig were evaluated. RESULTS: Mammalian expression vectors pIG/40Ig and p3.1/40Ig were constructed as described above. Chimeric proteins were expressed in COS-7 and CHO cell culture supernatant and confirmed by ELISA and Western blot. SDS-PAGE showed that fusion proteins had a disulfide-bonded dimeric structure and existed as homodimer. Purified CD40-Ig could bind to CD40L. In vivo administration of CD40-Ig could prevent the development of GVHD and significantly prolong the mean survival time of mice with graft-versus-host disease. CONCLUSIONS: These results demonstrate that CD40/CD40L interactions play an important role in the pathogenesis of graft versus-host disease and suggest clinical potential for CD40-Ig in the prevention and treatment of human graft-versus-host disease. PMID- 11780328 TI - High level expression of human factor VIII in mammalian cells after retroviral mediated gene transfer. AB - OBJECTIVE: To develop a retroviral-mediated high efficient expression system of human coagulation factor VIII. METHODS: The LNC-FVIIIBD retroviral vector was generated by cloning a human B-domain-deleted (760aa-1639aa) Factor VIII (FVIII) cDNA (FVIII cDNA BD) into the retroviral vector pLNCX. Several mammalian cell lines, including NIH3T3, CHO, Cos-7 and human hepatic cell line, L-02, were transduced with viral supernatant from the highest virus-producing PA317 clone. Antigen and coagulant activity of human FVIII in cell culture medium were measured by ELISA and a one-stage method, respectively. RT-PCR was performed for the detection of FVIIIBD mRNA. RESULTS: Human FVIII was expressed in all four target cells, with the highest FVIII expression observed in NIH3T3. The coagulant activity of secreted FVIII was up to 1.6 U/10(6) cells.24 hrs-1, and the FVIII antigen was 500 ng/10(6) cells.24 hrs-1. FVIII coagulant activity and antigen expressed by transduced CHO cells were 0.12 U/10(6) cells.24 hrs-1 and 62.4 ng/10(6) cells.24 hrs-1, respectively. Human FVIII expression was relatively low in Cos-7 and L-02 cells. RT-PCR results demonstrated transcription of FVIII cDNA BD in the target cells. CONCLUSIONS: The constructed retroviral vector was able to direct high level expression of human FVIII in various mammalian cell lines. It has potential utility in the future gene therapy for Hemophilia A. PMID- 11780329 TI - Detection of p53 gene mutations in sputum samples and their implications in the early diagnosis of lung cancer in suspicious patients. AB - OBJECTIVES: To evaluate the value of detecting p53 gene point mutations in sputum samples and its validity and reliability as a surveillance index in the early diagnosis of lung cancer in suspicious patients. METHODS: Sputum samples were collected from 54 cases identified as lung cancer and 114 cases identified as pulmonary benign disease. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was performed for the detection of point mutations at exons 5-8 of the p53 gene, and sputum smears were also used for each sample. RESULTS: The detected mutation rate of 55.56% (30/54) in the lung cancer group was significantly higher than that of 1.75% (2/114) in the control group (P < 0.001). In the lung cancer group, the sensitivity, specificity, and positive likelihood ratio (PLR) of p53 mutations as a diagnostic marker for lung cancer were 55.56%, 98.25% and 31.75%, respectively. Also, the detection rates were 35.19% (19/54) by smears and 55.56% (30/54) by PCR-SSCP-silver stain, respectively. The differences both in rate and consistency were statistically significant (P < 0.01 and P < 0.05, respectively). Moreover, statistical analysis showed no significant relations between p53 mutations and clinical parameters such as gender, smoking habits, histotypes and stages, but the detection rate of p53 mutations in older patients (> or = 60 years old) was significantly higher than that in younger patients (P = 0.02). One case with p53 mutations at exon 5 in the control group was confirmed to be squamous cell carcinoma after 4 years of follow-up. CONCLUSION: Detection of p53 gene alterations in sputum samples by PCR SSCP-silver stain can be used as a follow-up surveillance index for the early diagnosis of lung cancer in suspicious patients. PMID- 11780330 TI - Relationship between age and effect of early and long-term captopril treatment in patients with acute myocardial infarction. AB - OBJECTIVE: To analyse the relationship between age and treatment with captopril after acute myocardial infarction (AMI). METHODS: In a randomized trial, 822 patients with a first AMI received conventional medical treatment, including intravenous thrombolytic therapy and oral aspirin or metoprolol, and then were randomly allocated to captopril [dosage from the first 6.25 mg to 25 mg/t.i.d, 209 younger patients (< or = 64 years), 269 elderly patients (65-75 years)] or conventional treatment only (131 younger patients, 213 elderly). Survival in the four groups was calculated with the Kaplan-Meier method. Multivariate analysis was performed to understand the degree that multi-variables (including age) affect survival in patients taking captopril in the hospital or during long term follow-up. RESULTS: The survival of patients who took captopril correlated significantly with age (P < 0.001). The survival of the elderly patients on captopril treatment did increase (P < 0.0001), but not of the younger ones (P > 0.05) during hospitalization. During follow-up, the survival of patients who took captopril correlated insignificantly with age (P > 0.05), but both the elderly and the younger patients have good survival rates (all P < 0.01) and lower cardiac events (all P < 0.01) when they took captopril. CONCLUSIONS: Captopril exerts a weak effect on the younger patients but a beneficial effect on the elderly patients during hospitalization after AMI. However, there is no difference between the younger and the elderly in the prognosis, both having good survival and lower cardiac events when they take captopril long term during follow-up. PMID- 11780331 TI - Lack of correlation of vacA genotype, cagA gene of Helicobacter pylori and their expression products with various gastroduodenal diseases. AB - OBJECTIVE: To investigate the correlation among vacA genotypes, cagA gene, VacA, serum CagA antibodies of Helicobacter pylori (H. pylori) and gastroduodenal diseases. METHODS: vacA genotypes and cagA gene of 62 H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were tested by polymerase chain reaction, and Hela cell assay for VacA activity in vitro. Serum CagA antibodies were measured by EIA method in the same patients. RESULTS: All 62 H. pylori strains possessed the vacA gene and vacA genotypes of all strains were type s1a/m2. Total positive rate of cagA gene was 56.45%; the positive rates of cagA gene of H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were 55.56%, 54.17% and 63.64%, respectively (P > 0.05). The total positive rate of VacA was 37.10%; the positive rates of VacA produced by H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were 33.33%, 29.17% and 63.64%, respectively (P > 0.05). The positive rates of CagA antibodies in patients with chronic gastritis, peptic ulcer and gastric cancer were 70.37%, 79.17% and 40.00%, respectively (P > 0.05). The total positive rate of CagA antibodies was 68.85%. CONCLUSION: There was no correlation among cagA gene and vacA genotypes of H. pylori, VacA, serum CagA antibodies and various gastroduodenal diseases. PMID- 11780332 TI - Clinical evaluation of physical fitness in male obese Japanese. AB - OBJECTIVE: To establish an effective exercise prescription, the exercise capacity of obese subjects was investigated. METHODS: In 71 male obese (body mass index: BMI > or = 26.4) Japanese, aged 26-77 years, the body composition and physical fitness such as aerobic exercise level, muscle strength and flexibility were determined and compared with those of age- and sex-matched 71 borderline (24.2 < or = BMI < 26.4) and 71 normal Japanese men (19.8 < or = BMI < 24.2). The relationship between body composition and other parameters was evaluated in obese subjects. RESULTS: In obese subjects, body weight, BMI, body fat percentage, waist hip ratio, and skinfold thickness were higher than those of borderline and normal subjects. Lower aerobic exercise level and weight bearing index (WBI) were noted in obese subjects. There was a negative correlation between waist hip ratio and aerobic exercise level (oxygen uptake at ventilatory threshold) (r = -0.509, P < 0.01) and also between waist hip ratio and WBI (r = -0.315, P < 0.01). CONCLUSIONS: Lower physical fitness is considered to be a general characteristic of male obese Japanese, and the accumulation of visceral adipose tissue might affect exercise capacity. PMID- 11780333 TI - Determination of the dominant language hemisphere by functional MRI in patients with temporal lobe epilepsy. AB - OBJECTIVE: To determine the dominant language hemisphere in patients with intractable temporal lobe epilepsy before surgical treatment by using functional MRI (fMRI). METHODS: Twelve patients underwent fMRI. Among them, 4 patients also underwent the Wada test. Anterior temporal lobectomy was performed on patients with epileptic focus on the non-dominant hemisphere, and selective amygdalo hippocampectomy on patients with epileptic focus on the dominant hemisphere. RESULTS: Ten patients had left dominance, and 2 right dominance. The fMRI results were concordant with Wada test results in the 4 patients who accepted the Wada test. Seven patients underwent anterior temporal lobectomy, and 5 underwent selective amygdalo-hippocampectomy. There was no post-operative dysphasia. CONCLUSION: fMRI is an alternative method of noninvasive functional mapping for language dominance in patients with temporal lobe epilepsy. PMID- 11780334 TI - Cholinergic agonists increase intracellular calcium concentration in guinea pig vestibular hair cells. AB - OBJECTIVE: To better understand the cholinergic receptors in vestibular hair cells (VHC) and their subtypes, and to investigate the effects of cholinergic agonists on intracellular calcium concentration ([Ca2+]i) in guinea pig VHCs. METHODS: VHCs were isolated from guinea pig crista ampullaris by enzymatic and mechanical methods. The effect of cholinergic agonists on [Ca2+]i was examined using laser scanning confocal microscopy and the Ca2+ sensitive dye Fluo-3. RESULTS: The results showed that the addition of acetylcholine (ACh) and carbachol (CCh), muscamic and nicotinic agonists, induced [Ca2+]i increases in all the VHCs, whereas acetylcholine bromide (ACh-Br), a nicotinic agonist, induced the [Ca2+]i increase in only a small percentage of VHCs. The ACh or CCh induced Ca2+ response could be partially suppressed by atropine. In the presence of 0.1 mmol/L atropine, the amplitudes of ACh or CCh-induced [Ca2+]i responses became significantly smaller than those in atropine free medium (P < 0.01). CONCLUSIONS: The results suggest the existence of cholinergic receptors in guinea pig VHCs. It is the muscamic agonists rather than nicontic receptors that dominate [Ca2+]i variation. Atropine can suppress muscamic agonist-induced Ca2+ responses. PMID- 11780335 TI - LMP1 activates NF-kappa B via degradation of I kappa B alpha in nasopharyngeal carcinoma cells. AB - OBJECTIVE: To elucidate the mechanisms by which Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappa B in nasopharyngeal carcinoma cells. METHODS: A tetracycline-regulated LMP1-expressing nasopharyngeal carcinoma cell line, Tet-on-LMP1-HNE2, was used as the cell model. The kinetics of the expression of proteins, including LMP1, I kappa B alpha and I kappa B beta, was analyzed by Western blotting. The subcellular localization of NF-kappa B (p65) was detected by indirect immunofluorescence assay. The NF-kappa B transactivity was studied by transient transfection and reporter gene assay. RESULTS: I kappa B alpha was phosphorylated and degraded after the inducible expression of LMP1, although the total protein levels remained stable. The steady-state level of total I kappa B beta protein may have resulted from the initiation of an autoregulation loop after the activation of NF-kappa B. No change in the I kappa B beta level was detected. NF-kappa B (p65) was translocated from the cytoplasm to the nucleus following degradation of I kappa B alpha. After the introduction of the dominant-negative mutant of I kappa B alpha (Del 71) into Tet-on-LMP1-HNE2 cells, both nuclear translocation and transactivation of NF-kappa B induced by LMP1 was significantly inhibited. CONCLUSIONS: The results indicated that in nasopharyngeal carcinoma cells, LMP1 activated NF-kappa B via phosphorylation and degradation of I kappa B alpha, but not I kappa B beta. The dominant-negative mutant of I kappa B alpha (Del 71) could completely inhibit both the nuclear translocation and transactivation of NF-kappa B induced by LMP1. PMID- 11780336 TI - Direct protective effect of interleukin-10 on articular chondrocytes in vitro. AB - OBJECTIVE: To assess whether interleukin-10 (IL-10) is chondroprotective in vitro. METHODS: Chondrocytes were isolated from femoral cartilage of rats (7-10 days) by digestion with collagenase II. The first passage cells were grown in 24- well plates with DMEM, supplemented with 10% fetal bovine serum, for 2-4 days. The cells were then cultured in 0.1% fetal bovine serum DMEM medium, and given respectively interleukin-1 (IL-1) 100 mu/ml, IL-1 100 mu/ml + recombinant murine interleukin-10 (rmIL-10) 20 ng/ml, rmIL-10 20 ng/ml, and cultured for 48 hours. Scanning electron morphology and immunohistochemical study of nitric oxide synthase 2 and matric metalloproteinase 3 mRNA in situ hybridization were performed. Cell proliferation and morphology were observed under inverted microscope from the beginning of cell culture for three weeks. RESULTS: IL-1 stimulated granule production in the cytoplasma of chondrocytes, and the cells died in the second and third weeks of culture. IL-10 antagonized IL-1, protected the cells from death and maintained chondrocyte proliferation. Scanning electron morphology showed that IL-1 stimulated the formation of numerous microvilli on the cell surface, while thin and less numerous microvilli were found in cultures with IL-10. Immunohistochemical study and in situ hybridization showed that IL-10 inhibited NOS2 and MMP3 expression. CONCLUSION: IL-10 not only inhibits the synthesis of inflammatory cytokines, but also directly protects chondrocytes by antagonizing IL-1. PMID- 11780337 TI - A novel serine protease SNC19 associated with human colorectal cancer. AB - OBJECTIVE: To study the structure and function of a novel serine protease gene associated with human colorectal cancer SNC19. METHODS: The cDNA sequence was determined by both manual and automatic sequencing techniques. The full length cDNA sequence was obtained by the 5'-Rapid Amplification of cDNA Ends technique and web-based analysis. Open reading frame analysis and protein function prediction were also performed. Northern blot was used to detect the expression of SNC19 in various human normal tissues and tumor cell lines. Fluorescent in situ hybridization combined with fluorescent R-banding technique was employed to map the SNC19 gene on human chromosome. RESULTS: Full length SNC19 cDNA, size 3152 bp, encodes a protein highly homologous to a mouse serine protease epithin. In normal human tissues, high SNC19 expression levels were observed in the kidney, pancreas, prostate, small intestine and colon; moderate SNC19 expression levels were observed in the placenta, lung, liver, spleen thymus, testis and peripheral blood lymphocytes; and extremely low expression levels were observed in the heart, brain, skeletal muscle and ovary. In tumor cell lines, colorectal cancer cells SW480, SW620, SW1116 and Colo205, breast cancer cell Bcap37 and gastric cancer cells MKN28 and SGC7901 showed high levels of SNC19 expression; cervical cancer cell HeLa-S3, lung cancer PAA, oral epithelial cancer cell KB and lymphoma cell Raji showed moderate levels of SNC19 expression; and tongue squamous cancer cell Tca8113, leukemia cells HL-60, K562, MOLT-4, lung cancer cell A549 and melanoma cell G361 showed very low levels of SNC19 expression. SNC19 was mapped to human chromosome 11q24-25. CONCLUSION: SNC19 encodes a novel human serine protease with 855 amino acid residues. As a novel serine protease associated with human colorectal cancer, the expression of SNC19 in various tissues and cell lines may have very important impact on their phenotypes and biological behaviors. PMID- 11780338 TI - In-vitro cultivation of normal human oral keratinocytes. AB - OBJECTIVE: To establish a method for culturing normal human oral keratinocytes. METHODS: Specimens obtained from healthy humans undergoing oral surgery were dissociated into single cell suspensions by dispase and trypsin. The cells were grown in serum-free medium. Morphological characteristics were studied under light microscope and electron microscope. Cytokeratins were shown by immunohistochemistry. RESULTS: Cells could be maintained in culture up to 4-5 passages or 30-50 days. Electron microscope revealed that there were desmosomes and tonofibrils in the oral keratinocytes. The cells showed positive staining for cytokeratin antibody. CONCLUSION: Human oral keratinocytes have been successfully grown in serial culture. PMID- 11780339 TI - Liposome-C-erbB2 antisense oligodoxynucleotides in human ovarian cancer cells. AB - OBJECTIVE: To explore the effects of liposome-C-erbB2 antisense phosphorothioate oligodeoxynucleotides (S-ODNs) on C-erbB2 proto-oncogene expression and cell proliferation in human ovarian cancer cells. METHODS: The effects of liposome-C erbB2 S-ODNs on C-erbB2 protein expression, cell cycle and cell proliferation in human ovarian cancer cells were studied by means of flow cytometry and 3H thymidine incorporation. RESULTS: Liposome-C-erbB2 S-ODNs can specifically reduce C-erbB2 protein expression in human ovarian cancer cells, accompanied by a 30% inhibition of cell proliferation. The effectiveness of liposome-C-erbB2 S-ODNs on the expression of C-erbB2 was about 40 times higher than that of C-erbB2 S-ODNs. CONCLUSIONS: The data suggest that antisense therapy might be a useful method of gene therapy in ovarian cancer. The effectiveness of C-erbB2 S-ODNs could be greatly increased by adsorption of S-ODNs by liposomes. PMID- 11780340 TI - Mechanisms of multiple organ damages in acute necrotizing pancreatitis. AB - OBJECTIVE: To determine the role of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), and evaluate the progress from SIRS to MODS and the therapeutic strategies for acute necrotizing pancreatitis (ANP). METHODS: Rat ANP models were made by retrograde injection of 3.5% sodium taurocholate 2.5 ml/kg into the pancreatic duct. Serum interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF alpha), amylase, endotoxin, and albumin were examined. The morphology and pathology of the pancreas, liver, lung, kidney and heart after ANP were observed. Finally, TNF alpha mRNA in the liver, lung, kidney and heart after ANP were observed by reverse transcriptase-polymerase chain reactions, and the efficiency of somatostatin and growth hormone were also observed in this experiment. RESULTS: ANP led to remarkable elevation of the inflammatory mediators which were positively correlated with the development of ANP and MODS. Somatostatin and growth hormone inhibited inflammatory mediators and TNF alpha mRNA overexpressions, reduced the risk of MODS, corrected hypoalbuminemia, reversed negative nitrogen balance, and controlled the reduction of cell groups with functions and reasonably intervened SIRS caused by ANP. CONCLUSION: TNF alpha mRNA plays an important role in ANP progression. The amelioration of ANP by combination treatment with somatostatin and growth hormone leads to the reduction of complications and marked increase in survival. PMID- 11780341 TI - Epidemiological investigation of Histoplasma capsulatum infection in China. AB - OBJECTIVE: To provide reliable information concerning the presence or the absence of Histoplasma capsulatum (H. capsulatum) infection in China, and data concerning this respect. METHODS: Three hundred normal people and 435 hospitalized patients, who lived in Hunan and Jiangsu provinces, and the Xinjiang Autonomous Region, were tested with yeast-phase histoplasmin (ALK/Berkerley Biologicals Laboratories, USA) and human pure protein derivative of tuberculin (PPD) on the volar surface of the forearm. Any reaction to the antigens over 5.0 mm in diameter of induration at 48-72 hours was considered positive. RESULTS: A total of 138 subjects (18.8%) in 735 patients reacted to histoplasmin with 5.0-45.0 (9.1 +/- 4.3) mm indurations. Significant differences of positive skin reaction rates in normal subjects were found in Hunan, Jiangsu and Xinjiang (8.9% vs 15.1% vs 2.1%). The overall positive rate of patients was 25.5%. Patients with tuberculosis [31.7% (78/246)] had a significantly higher positive skin reaction rate in comparison with those suffering from pneumonia [17.7% (11/62)], lung cancer [20.9% (9/43)], chronic obstructive pulmonary disease [17.3% (9/52)] and other diseases [12.5% (4/32)] (P < 0.01). Of 562 cases, 292 cases (52.0%) reacted to PPD with indurations of 5-50 (13.7 +/- 4.9) mm in diameter, 63 cases (11.2%) reacted to both histoplasmin and PPD, while 38 cases (6.9%) reacted to histoplasmin but not to PPD. CONCLUSIONS: The data suggest that there is H. capsulatum herd infection in China. The infection rate in Southeast China is higher than that in the Northwest, and the infection rate of patients with pulmonary tuberculosis is higher than that of normal persons and other pneumonopathy patients. PMID- 11780342 TI - bcl 10 gene mutation in hepatocellular carcinoma. AB - OBJECTIVE: To detect the mutation frequency of the bcl 10 gene in the early and advanced stages of hepatocellular carcinoma (HCC). METHODS: Genome DNA samples were extracted from 46 cases of fresh HCC tumor tissues and their non-tumor adjacent tissues. Polymerase chain reaction-single strand conformation polymorphism method was used to detect point mutations of the three exons of the bcl 10 gene. For each individual exon, six random samples from those showing abnormal DNA bands were sequenced to verify those mutations. The relationship between serum alpha-fetoprotein (AFP) level and bcl 10 mutation, between the tumor size and bcl 10 mutation was also analyzed. RESULTS: Among the 46 samples, 26 cases (56.5%) were found to have mutations in exon 1, 5 out of the 6 cases were shown to have 5744 C-->G mutation by sequencing; 25 cases (54.3%) were found to have mutations in exon 2, 4 out of the 6 cases were shown to have 11,311 T deletion mutation by sequencing. Twenty-one cases (45.7%) were found to have mutations in exon 3, all of the 6 cases selected for sequencing were shown to have 14,116 C-->T mutation. Statistical analysis showed that neither serum alpha fetoprotein level nor the size of hepatocellular carcinoma has a significant relationship with bcl 10 mutation. CONCLUSION: The bcl 10 gene has a high mutation frequency in liver cancer. PMID- 11780343 TI - Surgical treatment of 52 patients with congenital coronary artery fistulas. AB - OBJECTIVE: To evaluate the outcome of surgical treatment for congenital coronary artery fistulas (CAF) in 52 patients seen between May 1988 and July 1999. METHODS: Fifty-two patients ranging in age from 9 months 58 years (mean 15.7 +/- 16.4 years) were studied. Thirty-six patients had no other cardiac defects, 9 of those patients were more than 20 years old and presented with symptoms. Only one of 36 patients less than 20 years old had clinical findings before surgery. Sixteen patients had associated cardiac lesions. The site of fistula origin was the right coronary artery in 37 patients (71.2%), and the left coronary artery in 15 patients (28.8%). The sites of CAF drainage were the right ventricle, right atrium, left ventricle, left atrium and pulmonary artery in 22 (42.3%), 16 (30.8%), 6 (11.5%), 3 (5.8%), and 5 (9.6%) patients, respectively. The mean diameter of the fistula in 43 patients with single ostium was 7.34 +/- 4.12 mm. RESULTS: Cardiopulmonary bypass was used in all patients and no patient died. An arteriotomy was made on the anomalous coronary artery and the proximal opening of a fistula was closed within the vessel in 10 patients. Closure of the distal opening of a fistula draining into a cardiac chamber or pulmonary artery was performed in 26 patients. In 16 patients, both the proximal and distal opening were closed. Two and 3 distal opening of a fistula were found in 6 and 3 patients, respectively. No residual shunt was found before patients were discharged from the hospital. Forty patients were followed up for a mean period of 3.14 +/- 1.84 years. The remaining 12 patients could not be contacted during follow-up. No clinical symptoms were found in those patients during follow-up but one patient still presented with ST-T change. CONCLUSION: Early and properly surgical management is safe and effective for congenital coronary fistula. PMID- 11780344 TI - Comparison of CT virtual endoscopy with electronic colonoscopy in 30 colonic carcinoma patients. AB - OBJECTIVE: To evaluate the clinical application of CT virtual endoscopy (CTVE) in the diagnosis and treatment of colonic carcinoma. METHODS: We collected 30 patients pathologically proven to have colonic carcinomas as examined by CTVE and electronic colonoscopy (EC), correlating the CTVE and EC images respectively with surgical pathology in three aspects: tumor morphological features, degree of circumferential bowel wall involvement and longitudinal extent of tumor. RESULTS: CTVE imaging of colonic carcinomas showed morphological features: polypoid pattern (11 patients), ulcerative pattern (11), and infiltrative pattern (8); degree of circumferential bowel wall involvement: less than 1/2 (4 patients), from 1/2 to 3/4 (6), and more than 3/4 (20); and their longitudinal extent: 1.0 3.0 cm (7 patients), 31-5.0 cm (10), and 5.1-11.0 cm (13). Correlation of CTVE and EC with surgical pathology was found. Comparison of CTVE with surgical pathology showed tumor morphological features: concordant (26 patients), and disconcordant (4); degree of circumferential bowel wall involvement: concordant (25), disconcordant (5); and longitudinal extent of the tumor: concordant (23), disconcordant (7). Comparison of EC with surgical pathology showed tumor morphological features: concordant (22 patients), disconcordant (8); degree of circumferential bowel wall involvement: concordant (28), disconcordant (2); and longitudinal extent of the tumor: concordant (14), disconcordant (3), and undefined by EC (13). CONCLUSIONS: The images obtained by CTVE in colonic carcinoma are similar to those obtained by EC. CTVE is an excellent alternative to EC for patients who cannot tolerate EC and for cases with incomplete EC. PMID- 11780345 TI - Epitope mapping on Wegener's granulomatosis autoantigen proteinase 3. AB - OBJECTIVE: To map the epitopes on Wegener's granulomatosis autoantigen proteinase 3. METHODS: Antigenicity of proteinase 3 was studied with Western blot analysis in which proteinase 3 was prepared under reducing and non-reducing conditions. Two anti-proteinase 3 monoclonal antibodies, HZ1F12 and HZ1H3, were used to inhibit each other and to inhibit 22 anti-proteinase 3 positive sera from patients with Wegener's granulomatosis in competitive inhibition enzyme-linked immunosorbent assays (ELISA) and Western blot analysis. RESULTS: All monoclonal antibodies and patient sera recognized proteinase 3 under non-reducing conditions in Western blot analysis. ZH1F12 was inhibited 74% by HZ1H3. 10/22 (46%) sera were completely or partially inhibited by HZ1F12; 9/22 (41%) sera were partially inhibited by HZ1H3; and 6/22 (27%) were inhibited by both monoclonal antibodies. In inhibition Western blot analysis, the binding of patient sera to proteinase 3 could be inhibited by HZ1F12. CONCLUSIONS: The epitopes of Wegener's granulomatosis autoantigen were conformational. Anti-proteinase 3 monoclonal HZ1F12 and HZ1H3 recognized similar or overlapping epitopes on the proteinase 3 molecule. Epitopes of proteinase 3 recognized by anti-proteinase 3 positive sera were not restricted. PMID- 11780346 TI - Intrathecal injection with methotrexate plus dexamethasone in the treatment of central nervous system involvement in systemic lupus erythematosus. AB - OBJECTIVE: To investigate the effect of intrathecal injection (i.t.) with methotrexate (MTX) plus dexamethasone (DXM) in treating central nervous system involvement in systemic lupus erythematosus (CNS lupus). METHODS: Twenty-four CNS lupus patients that were refractory to conventional steroid therapy were selected for i.t. with MTX 10-20 mg plus DXM 10-20 mg. The effects and side effects of i.t. were closely observed. RESULTS: The symptoms and signs of 22/24 (91.7%) CNS lupus patients receiving i.t. improved considerably. Cerebrospinal fluid pressure, protein and WBC levels declined from 201.5 +/- 155.4 mm H2O, 145.2 +/- 87.6 mg/dl and 25.1 +/- 14.3/mm3 to 128.7 +/- 108.1 mm H2O, 60.8 +/- 38.3 mg/dl and 6.8 +/- 2.1/mm3 respectively. Transient side effects were observed in 4 patients: 1 with itching sensation of lower limbs, 2 with headache and 1 with incontinence. CONCLUSION: I.t. with MTX plus DXM is a promising method for treating CNS lupus and deserves further investigation. PMID- 11780347 TI - Pathogen of root surface caries in the elderly. AB - OBJECTIVE: To study the pathogen of root surface caries in the elderly. METHODS: Plaque samples from the experimental group and the control group were collected. After culturing in selective and non-selective media, the different bacteria were isolated. The counts and the positive rates of total bacteria, porphyromonas group, pervotella group, streptococcus mutants group, actinomyces group and lactobacillus group were compared. RESULTS: The counts of total bacteria, streptococcus mutants, actinomyces and lactobacillus of the experimental group were higher than those of the control group. The positive rates of actinomyces and lactobacillus of the experimental group were significantly higher than those of the control group. CONCLUSION: Actinomyces and lactobacillus are the main related pathogens of root surface caries in the elderly. PMID- 11780348 TI - Policy making and organization in managing tropical diseases in China. PMID- 11780349 TI - Preliminary study on immunotoxin for the prevention of Schistosomiasis japonica. PMID- 11780350 TI - Diagnosis and surgical treatment of temporal lobe epilepsy. AB - OBJECTIVE: To discuss the diagnosis and surgical treatment of temporal lobe epilepsy. METHODS: From 1996 to 1998, 36 patients presenting with medically intractable temporal lobe epilepsy were identified by EEG and MR, including volumetric MR, for hippocampal formation. Among them, 16 patients underwent anterior temporal lobectomy, while 20 patients accepted selective amygdalohippocampectomy. The results of surgical operation and follow-up are analyzed. RESULTS: With respect to seizure outcome, all patients benefited from surgery. The surgical results were satisfactory in 24 cases, notable in 11 cases, and good in 1 case, and there were no complications. CONCLUSION: MR is beneficial for the localization of epileptic foci. Surgery is an effective method for the treatment of temporal lobe epilepsy; selective amygdalohippocampectomy is the first choice for medial temporal lobe epilepsy. The transzygmatic-temporal lobe base approach presented in this study improved the safety of the surgery. PMID- 11780351 TI - Effects of extrinsic positive end-expiratory pressure on work of breathing in patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: To investigate the effects of extrinsic positive end-expiratory pressure (PEEPe) on work of breathing in patients with chronic obstructive pulmonary disease (COPD) and their corresponding mechanism. METHODS: Ten ventilated patients with COPD were included in the study. A Bicore CP-100 pulmonary monitor (Bicore Monitoring System, USA) was used for monitoring respiratory mechanics. First, dynamic intrinsic positive end-expiratory pressure (PEEPi, dyn) was measured when PEEPe was zero, which was called PEEPi, dynz. Then the PEEPe was set randomly at 0%, 40%, 60%, 80% and 100% of PEEPi, dynz respectively. Pulmonary mechanics and other parameters (heart rate, blood pressure and blood gas analysis) were measured 30 minutes after the level of PEEPe was changed. RESULTS: Work of breathing patient (WOBp), pressure time product, difference of esophageal pressure and PEEPi, dyn decreased significantly when PEEPe was applied, and continued decreasing as PEEPe was increased. Work of breathing ventilator increased significantly when PEEPe was increased to 80% and 100% of PEEPi, dynz. Significantly positive linear correlation was found between the changes in WOBp and in PEEPi, dyn. CONCLUSIONS: WOBp decreases gradually as PEEPe is increased. WOBp decreases by narrowing the difference between the alveolus pressure and the central airway pressure at the end of expiration when PEEPe is applied. PMID- 11780352 TI - Management of hemangiopericytomas in the central nervous system. AB - OBJECTIVE: To elucidate the clinical features and treatment of Hemangiopericytomas (HPCs) in the central nervous system. METHODS: Twenty-six HPC operations performed at Huashan Hospital from January 1993 to June 1999 were analyzed retrospectively, and a review of relevant literatures was done. RESULTS: Among the 26 cases, total tumor removal was achieved in 24 cases, and subtotal removal in 2 cases. Postoperatively, neurological symptoms were improved or unchanged in 21 cases, worsened in 4 cases, and pneumonia caused death in 1 case. Eighteen patients received postoperative radiotherapy. Eighteen patients were followed up from 1 month to 58 months (average, 22 months). During the follow-up period, 2 patients presented one or more distant metastasis, and one patient died of recurrence. CONCLUSION: Surgical management is the best choice for treatment of patients with HPCs. Postoperative radiotherapy can postpone the risk of tumor recurrence. PMID- 11780353 TI - Inherited disturbances of phenylalanine metabolic kinetics in essential hypertension. AB - OBJECTIVE: To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH). METHODS: 1. L-(2, 3D3)-leucine, L (2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n = 10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n = 12, FS+) and those without genetic predisposition of EH and stroke (n = 12, F) groups. 2. By comparing the radioactive counts of [3H] phe, and their weight transformation in blood after 1.5 Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of [3H]-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were compared. RESULTS: A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular tissue. CONCLUSION: A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies. PMID- 11780354 TI - Hepatic artery angiography and embolization for hemobilia after hepatobiliary surgery. AB - OBJECTIVE: To evaluate the effectiveness of hepatic angiography and embolization in the diagnosis and treatment of hemobilia after hepatobiliary surgery. METHODS: Nine patients had upper gastrointestinal bleeding 7 days to 3 months after surgery. They underwent emergency hepatic artery angiography and were treated by embolization using Gelfoam particles only (8 patients) and Gelfoam particles plus microcoils (1 patient). RESULTS: Hepatic artery angiography revealed hepatic artery pseudoaneurysms in 3 patients, diffuse hemorrhage of the hepatic artery branches in 3, right hepatic artery-bile duct fistulas in 2, and hepatic artery small intestine fistula in 1. Hemobilia was controlled with embolization in 7 patients, of whom 1 had recurrent bleeding 1 day after treatment. During the follow-up, 3 patients died of multiple organ dysfunction syndrome. Two patients whose hemorrhage could not be controlled due to technical reasons died several days later. CONCLUSION: When hemobilia after hepatobiliary surgery is suspected, patients should receive hepatic angiography as a first diagnostic procedure and be treated with minimally invasive procedure of selective embolization of the involved artery as soon as possible. PMID- 11780355 TI - Suppression subtractive hybridization for identifying differentially expressed genes in renal cell carcinoma. AB - OBJECTIVE: To construct a renal cell carcinoma (RCC) cDNA subtractive library using suppression subtractive hybridization. METHODS: Polyadenylated RNA [Poly (A)+ RNA] was isolated from tissues of RCC and normal kidney, and single-strand cDNAs and double-strand cDNAs were synthesized in turn. RCC cDNAs were divided into two groups and ligated to the specific adaptors I and 2, and then hybridized with normal kidney cDNA twice with two rounds of suppression PCR. Second round PCR products were cloned to T/A plasmid vectors to set up the subtractive library. One hundred clones were randomly picked to perform enzyme digest analysis, and some underwent sequence analysis and Northern blot to identify RCC specifically expressed genes. SMART RACE procedure was operated to clone full length novel RCC specifically expressed genes. RESULTS: A human RCC subtractive library with high subtractive efficiency was successfully set up. The amplified library contains 350 positive clones. Random analysis of 100 clones with enzyme restriction showed that 85 plasmids in the clones contained 50-400 bp inserts. Sequence analysis was performed for 10 clones. All the 10 sequences were unknown before and derived from 6 unique, novel genes among which the cDNA insert RCC18 had five copies. Northern blot analysis showed that RCC18 cDNA was highly expressed in RCC, but no signal could be detected in normal kidney. Using SMART RACE technique, we obtained the full length of the novel gene RCC18. CONCLUSIONS: The constructed cDNA subtractive library of human RCC is a highly efficient one and lays a solid foundation for large scale screening and cloning new and specific oncogenes or tumor suppressor genes of RCC. The novel specifically expressed genes provided an important clue for studying the mechanisms of occurrence and development of RCC. PMID- 11780356 TI - Effects of peripheral blood mononuclear cells from idiopathic nephrotic children on cultured rat glomerular epithelial and mesangial cells. AB - OBJECTIVE: To investigate the effect of immune cell from idiopathic nephrotic children on extracellular matrix (ECM) synthesis by cultured rat glomerular epithelial cell (GEC) and on the proliferation of mesangial cell (GMC). METHODS: Twenty-eight children with idiopathic nephrotic syndrome and 15 age-matched healthy children were randomly selected and divided into 4 groups: Group 1, untreated nephrotic children; Group 2, glucocorticoid treated nephrotic children; Group 3, children undergoing glucocorticoid treatment with negative proteinuria; and Group 4, normal control. The peripheral blood mononuclear cells (PBMC) were collected from these children and PBMC conditioned medium (PBMC-CM) were prepared. The PBMC-CM was co-cultured with GEC and GMC respectively. The concentrations of collagen, laminin, collagen III and collagen IV in the GEC and PBMC-CM co-culture medium were investigated. The GMC proliferation was measured by the 3H-thymidin incorporation method. RESULTS: The 3H-proline incorporation coefficients of the GEC treated with the PBMC-CM of the 4 groups were 0.93, 1.24, 1.23, and 1.11, respectively. The laminin inhibitory coefficients of the 4 groups were 0.95, 1.02, 1.01, and 1.04, respectively. The inhibitory coefficients of collagen III were 0.97, 1.00, 0.99, and 1.01, respectively, for the 4 groups. All these parameters showed a significant difference between Group 1 and the other 3 groups (P < 0.05). However, there was no significant difference in the inhibitory coefficient of collagen IV between each two of the 4 groups (1.04, 1.05, 1.04, 1.08, P > 0.05). The 3H-thymidine incorporation coefficients of GMC responsive to PBMC-CM were 1.21, 1.53, 1.50, and 1.10, respectively, and no significant difference was found between the 4 groups (P > 0.05). CONCLUSION: The results suggested that the circulating immune cells from idiopathic nephrotic children have a direct effect on some ECM component synthesis in cultured rat GEC; the bio activity of immune cells could be neutralized by administering glucocorticoid; and the circulating immune cells of nephrotic children have no direct effect on GMC proliferation. PMID- 11780357 TI - Apolipoprotein E gene polymorphism and its association with human longevity in the Uygur nationality in Xinjiang. AB - OBJECTIVE: To study the relationship between apoE alleles and life-span. METHODS: Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction by using polymerase chain reaction-restriction fragment length polymorphism. Apolipoprotein E gene polymorphism was analyzed among three groups. RESULTS: There was statistically significant difference in the epsilon 4 allele frequencies among three groups. The epsilon 4 allele frequency in olds was the lowest (0.057), while in patients suffering from myocardial infarction (MI) was the highest (0.213). In MI patients the average age of first attack in epsilon 4 allele carriers was significantly younger than that of non-carries, 51.3 and 58.3 years, respectively (P < 0.05). CONCLUSION: ApoE genotype may have some impact on human longevity. PMID- 11780358 TI - The effect of magnetic stent on coronary restenosis after percutaneous transluminal coronary angioplasty in dogs. AB - OBJECTIVE: To investigate the effects of magnetic stents on coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Twenty dogs were randomly divided into the control and experimental groups, each with 10 dogs. The control group was given common Palmaz-stents in the 6-8 segment of left anterior descending coronary artery or in the 11-14 segment of the left circumflexus. The experimental group was given magnetic stents in the same parts of the coronary arteries. The dogs were not given antiplatelet or anticoagulant drugs before or after the operation. Six months later, the 20 dogs were subjected to coronary angiographies, and then were sacrificed. Three centimeter long segments of the target vessels were cut for pathological examination. RESULTS: The degree of restenosis in 3 dogs of the control group was more than 50%, but none in the experimental group experienced restenosis. The average thickness of the tunica intima of the target artery was 2.98 +/- 0.56 mm in the control and 1.13 +/- 0.41 mm in the experimental group (P < 0.05). CONCLUSION: Magnetic stents could have a significant preventive effect on coronary restenosis. PMID- 11780359 TI - Identification and function of glucose transporter 1 in human mesangial cells. AB - OBJECTIVE: To evaluate the role of glucose transporter 1 (GLUT1) in the glucose uptake of glomerular mesangial cells. METHODS: Cultured human glomerular mesangial cells were used. The expressions of glucose transporter 1 mRNA and protein were detected with reverse transcription-polymerase chain reaction (RT PCR), flow cytometry and immunofluorescence staining. Glucose uptake was determined with 2-deoxy-[3H]-D-glucose uptake assay. RESULTS: The expressions of GLUT1 mRNA and proteins were detected in human mesangial cells. Glucose uptake and its kinetics assay showed that GLUT1 is a functional glucose transporter in cultured human mesangial cells, and that its function could be inhibited by the specific inhibitor, Phloretin. CONCLUSION: GLUT1 is the predominant glucose transporter in human mesangial cells, which has the kinetic characteristics of high affinity and low capacity for D-glucose. This suggests that in order for mesangial cells to take up excessive quantities of glucose, as in diabetes, changes in glucose transporter expression, translocation or activity may be required. PMID- 11780360 TI - Regulation of osteopontin expression in a rat model of urolithiasis. AB - OBJECTIVE: To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis. METHODS: Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3(D3), vitamin K, testosterone or estradiol for 7 days, and the expression of osteopontin and its mRNA were detected with immunohistochemistry and Northern blot, respectively. Crystals deposited in rat kidneys were observed with a polarization microscope. The concentrations of crystal components in rat urine were determined. RESULTS: The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys. D3 increased the concentration of calcium in urine, and accelerated the sedimentation of calcium oxalate in rat kidneys. CONCLUSIONS: These findings indicate that OPN may be an important macromolecule in the normal endogenous inhibition of the formation of urolithiasis. Vitamin K, testosterone and estradiol inhibit the formation of stones via up-regulating the expression of OPN in kidneys, while D3 over dose may accelerate the process. PMID- 11780361 TI - The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats. AB - OBJECTIVE: To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. METHODS: The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3H-TdR incorporation and was confirmed with histological analysis. RESULTS: Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. CONCLUSION: HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension. PMID- 11780362 TI - Construction of a recombinant plasmid harbouring the rhoptry protein 1 gene of Toxoplasma gondii and preliminary observations on DNA immunity. AB - OBJECTIVE: To observe the immune responses elicited in BALB/c mice by a DNA vaccine. A gene encoding rhoptry protein 1 (ROP1) from Toxoplasma gondii (T. gondii) was cloned into vector pcDNA3. METHODS: Amplifyied gene fragments coding for ROP1 from the genomic DNA of T. gondii ZS2 were inserted into cloning vector, pUC18, and sub-cloned into pcDNA3. Mice were injected at a dosage of 100 micrograms recombinant plasmid DNA by intramuscular injection and boosted after 2 weeks. pcDNA3 and normal saline were used as control. 30, 50 and 70 days after the second immunization, NK cell activity, T lymphocyte proliferation and sub clusters and serum IgG antibody were assayed. RESULTS: The specific gene fragment coding for ROP1 was amplified and a pcROP1 recombinant was constructed. At 30 days after immunization, the spleens of the mice were obviously enlarged evidently. NKC activity and the proliferation of spleen T lymphocytes seen on MTT assay were higher in pcROP1 group than in the controls. The number of CD4+ T cells exhibited no obvious increase compared with that of the control, but CD8+ T cells were obviously increased (P < 0.05). At 90 days after vaccination, the titer of IgG antibody in the serum of vaccinated mice was positive (1:100). CONCLUSION: pcROP1 was constructed and it could elicit both cellular and humoral immune responses in immunized mice. PMID- 11780363 TI - Clinical manifestations of AIDS with cryptococcal meningitis. AB - OBJECTIVE: To increase the awareness of AIDS with cryptococcal meningitis. METHODS: Eighteen cases of confirmed AIDS with cryptococcal meningitis in the Bata Regional Hospital, Equatorial Guinea from January 1997 to November 1999 were analyzed. RESULTS: The clinical manifestations of the 18 cases were: insidious onset, fever, severe headache, generalized pain, nausea and vomiting, weight loss and dehydration, and enlarged cervical lymph nodes. Boa's and Cullen's signs were positive. The positive rates of cerebrospinal fluid (CSF) India ink stain and the polysaccharide capsule antigen (ELISA) were 77.8% and 99.4%, respectively. The positive rate of CSF culture of cryptococcus was 100%. The mortality rate was 83.3%. CONCLUSION: Cryptococcal meningitis is the most common opportunistic infection and one of the major causes of deaths in AIDS patients. The misdiagnosis and mortality rates were very high and could be explained by a lack of awareness for the occurrence of AIDS with cryptococcal meningitis, late presentation, serious illness and severe complications, and delayed and inadequate therapy. PMID- 11780364 TI - Immune responses to the expressed products of the CSP antigen gene of plasmodium falciparum southern China isolate FCC1/HN in Hela cell. AB - OBJECTIVE: To construct a eukaryotic expression system with pcDNA3-PfCSP/Hela for the Circumsporozoite protein (CSP) gene of Plasmodium falciparum (P. falciparum), to observe the immune responses in BALB/c mice induced by the expressed proteins. METHODS: The recombinant plasmid pcDNA3-PfCSP was transformed into the Hela cell line. The expressed protein was isolated and analyzed by using SDS-PAGE and used for immunization of BALB/c mice by subcutaneous, intravenous, and intraperitoneal administration. Enzyme-linked immunosorbent assay (ELISA), Dot-ELISA, Western blot, T lymphocyte proliferation test, natural killer cell (NKC) activity assay, and CD4+ and CD8+ T cell detection were used for observation of humoral and cellular immune responses. RESULTS: Immune sera strongly reacted with the expressed protein, antibody titer was up to 1:6400 as detected by ELISA. Western blot analysis revealed a specific band at 38.3 Kda. When the spleen cells of normal and immunized BALB/c mice were specifically stimulated with expressed protein, the optical densities were 0.12 +/- 0.03 and 0.34 +/- 0.04, respectively. The latter were significantly higher than the former (P < 0.01). We used the MTT colorimetric assay to measure NKC activity of mice spleen. The results showed that the NKC activity of immunized BALB/c mice was remarkably higher than that of the controls (P < 0.05). CD4+ and CD8+ T cells were detected by using monoclonal antibody immunofluorescence methods. The results showed that the percentage of CD4+ and CD8+ T cells of immunized group were significantly higher than that of control group (P < 0.05). CONCLUSIONS: The humoral and cell mediated immune responses and elevated NKC activity to products made with a eukaryotic expression system could be specifically detected in BALB/c mice. These findings indicate that the expressed protein could enhance the immune function in mice. PMID- 11780365 TI - Regional glucose metabolic increases in left auditory cortex in tinnitus patients: a preliminary study with positron emission tomography. AB - OBJECTIVE: To investigate the relationship between tinnitus and glucose metabolism in auditory cortex and whether positron emission tomography (PET) can be an objective tool in measuring tinnitus. METHODS: Eleven right-handed patients with severe tinnitus and ten right-handed control subjects participated in the 18F-FDG/PET study. Analysis with regions of interests was used to calculate asymmetry indices according to the formula: [(L-R) x 100/[(L + R) divided by 2]]. RESULTS: Glucose metabolism in the auditory cortex of tinnitus patients was asymmetric between the left and right auditory cortices, with that of the left being much higher than that of the right. The asymmetry indices of tinnitus patients was significantly higher than that of the control group (unpaired t test, P < 0.001). This revealed that the increased metabolic activity was present in the predominant left hemisphere with a significant focus on the superior and transverse temporal gyri (Brodmann areas 41 and 42, respectively corresponding to primary and secondary auditory cortex), and the results were independent of the subjective localization of the tinnitus sensation. CONCLUSION: It is suggested that the increased metabolism in the left auditory cortex is related to the tinnitus sensation. PET is capable of providing objective evidence for tinnitus and may be used as a potential tool in measuring tinnitus. PMID- 11780366 TI - Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor. AB - OBJECTIVE: To explore the characteristics of oncoprotein expression of c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor (bFGF). METHODS: Tissues of hypertrophic scars (n = 8), chronic dermal ulcers (n = 8) and normal skin (n = 5) were taken from 21 patients with burns and chronic dermal ulcers in operation. The ABC immunohistochemical method was used to characterize the gene product expression of c-fos, c-jun and bFGF in the above tissues. RESULTS: In normal skin, both c fos and c-jun protein expression and bFGF protein expression were observed. The signals of both oncoproteins were localized mainly in subcutaneous fibroblasts, but, positive expression of the bFGF protein was mainly in keratinocytes. In hypertrophic scars, positive expression of both oncoproteins could be found mainly in fibroblasts, but bFGF was mainly in fibroblasts and endothelial cells. In chronic dermal ulcers, endothelial cells, some of inflammatory cells and fibroblasts were positive for both of oncoproteins, but the expression of bFGF was only seen in fibroblasts and endothelial cells. CONCLUSIONS: The results indicate that the interaction between both oncoproteins and bFGF exists, and the regulating action between protooncogenes and bFGF is a major course in wound healing. The different expressions of c-fos and c-jun gene products play an important role in regulate bFGF action, thus affecting wound healing. PMID- 11780367 TI - Replacement of the p16 gene in human ovarian cancer cells. AB - OBJECTIVE: To study the inhibitory effects of retrovirus-mediated p16 gene on the human ovarian cancer cell line CAOV3. METHODS: The recombinant eukaryotic expression vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector with neomycin resistance gene only were introduced into a CAOV3 cell line which does not express p16 endogenously by lipofectamine-mediated gene transfection. By using polymerase chain reaction amplification, mRNA in situ hybridization and immunocytochemistry, the clones obtained were tested for their efficiency of transfection and effects of vector expression. Their biologic behavior was observed further. RESULTS: Exogenous wt-p16 was transferred into CAOV3 cells successfully and permanent expression was obtained. The growth rate of the transfected CAOV3 cells in regular medium and soft agar was inhibited, and the tumorigenicity in nude mice showed that two of four mice failed to form tumors, and the others developed tumors 7 to 14 days later than mice of the contrast group. The percentage of phase G1 cells increased and that of phase S cells decreased. Under electron microscope, the ultrastructural changes of the cells revealed necrosis and growth retardation. CONCLUSIONS: The p16 gene plays an important role in the generation and development of ovarian carcinoma. This study might provide experimental evidence for gene therapy in human ovarian cancer. PMID- 11780368 TI - Murine antibody against E2 can capture hepatitis C virus in vitro. AB - OBJECTIVE: To find neutralizing antibody candidates against hepatitis C virus (HCV) infection. METHODS: We constructed two eukaryotic expression vectors which contained the E1 and E2 gene of HCV, and detected their expression in mammalian cells with transient expression. BALB/c mice were given subculaneous injections of constructed vectors combined with the IL-2 gene intraepidermally and evaluated for induced humoral immune responses by enzyme-linked immunosorbent assay (ELISA). We used an antibody-virus interaction assay to analyze the interaction of the antisera and HCV viral particles in vitro. RESULTS: Anti E1 and anti-E2 antisera were obtained from immunized mice. The serum of mice immunized with the E2 gene immunoprecipitated the HCV isolate in source serum and reacted with the isolates unrelated to the original one. CONCLUSIONS: Anti-E2 antibody in induced mice can cross-reactively capture HCV particles, highlighting the possibility of generating broadly reactive anti-E2 antibodies. PMID- 11780369 TI - Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis. AB - OBJECTIVE: To investigate the pattern of monocyte chemoattractant prolein-1 (MCP 1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed. METHODS: Eighteen female patients with biopsy proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. RESULTS: MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4 +/- 6.2% vs 26.7 +/- 22.8%, P < 0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r = 0.5420, P < 0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r = 0.0547, P > 0.05). CONCLUSIONS: The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis. PMID- 11780370 TI - Changes in intestinal microflora in patients with chronic severe hepatitis. AB - OBJECTIVE: To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease. METHODS: We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and liver function were assessed. RESULTS: The number of fecal bifidobacterium (P < 0.001, P < 0.05 respectively), as well as bacteroidaceae (P < 0.001, P < 0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P < 0.001, P < 0.05 respectively) and yeasts (P < 0.01, P < 0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-alpha, IL-1 beta and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-alpha, IL-1 beta and TBiL (P < 0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P < 0.05, P < 0.001, respectively). CONCLUSION: Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut microbiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure. PMID- 11780371 TI - Detection of human herpesvirus 8 DNA in acute leukemia patients. AB - OBJECTIVE: To determine the prevalence of human herpesvirus 8 (HHV-8) DNA in acute leukemia (AL) patients. METHODS: The presence of HHV-8 DNA sequences in peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) from 50 AL patients was examined using polymerase chain reaction (PCR). Nine human hematopoietic cell lines and PBMC from 30 normal donors were also included. RESULTS: HHV-8 DNA sequences were detected in one case of acute myelogenous leukemia (AML). The specimens from the bone marrow aspirate, peripheral blood and serum of this patient were all positive. None of the normal donors and human hematopoietic cell lines showed evidence of HHV-8 DNA. CONCLUSION: The results suggest that the prevalence of HHV-8 is low in AL in China. PMID- 11780372 TI - Confirmation of susceptibility gene loci on chromosome 1 in northern China Han families with type 2 diabetes. AB - OBJECTIVE: To confirm previous effort to identify type 2 diabetes susceptibility genes in a Northern Chinese population by conducting a new genome scan with both an increased number of type 2 diabetes families and a new set of microsatellite markers within the previously localized regions. METHODS: A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, we obtained size information for all loci, and then a further study was done by both parametric and non-parametric linkage analysis to investigate the P values and Z values of these loci. RESULTS: We surveyed 34 microsatellite markers which distributed within 5 regions along chromosome 1, and a total of 12,000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci. All P values of the 8 loci were lower than 0.05, and the highest Z value was 2.17. A very interesting finding is that all 5 markers at the p- terminal 1p36.3-1p36.23 region, spanning a long range of 16.9 cM, were identified to have a low P value of less than 0.05, which suggests that this region may contain multiple susceptibility genes. Regions 4 and 5 also confirmed the previous findings, and we narrowed these two regions to a 2.7 cM and 2.5 cM regions, respectively. CONCLUSIONS: We further confirmed the results gained in the previous genome-wide scan using an increased number of NIDDM families and a new set of microsatellite markers lying within the initially localized regions. The fact that all 5 loci at the p- terminal region displayed a low P value of less than 0.05 suggests that more than 1 susceptibility gene may reside in this region. PMID- 11780373 TI - Laparoscopic resection for a left adrenal black adenoma. PMID- 11780374 TI - The effect of herbs on cerebral energy metabolism in cerebral ischemia reperfusion mice. PMID- 11780376 TI - Urinary excretion of aquaporin-2 water channel protein in chronic heart failure rats. AB - OBJECTIVE: To study the urinary excretion of aquaporin-2 (AQP2) water channel protein, and the relationship between urine AQP2 concentration and renal AQP2 gene expression in chronic heart failure (CHF) rats. METHODS: Male Sprague-Dawley rats (200 g-250 g) underwent either a left coronary artery ligation, a model of CHF, or a sham-operation. Nine weeks after surgery, urinary AQP2 concentrations and renal AQP2 protein levels were measured by Western blot. RESULTS: The urinary concentration of AQP2 water channel protein increased significantly in CHF rats as compared with sham-operated rats (365.6% +/- 102.9% vs 98.5% +/- 47.6%, P < 0.01). There was positive correlation between urinary AQP2 concentration and renal AQP2 protein expression (r = 0.89, P < 0.01). CONCLUSION: The urinary concentration of AQP2 water channel protein increases significantly in chronic heart failure rats. PMID- 11780377 TI - Histochemical study of transmyocardial laser channels in dogs. AB - OBJECTIVE: Laser-induced myocardial injury was investigated in a canine transmyocardial laser revascularization model. METHODS: A total of 23 channels were created in the left ventricles of 5 animals with a CO2 laser. Four animals were sacrificed immediately and one at week 2. Lactate dehydrogenase and succinate dehydrogenase in channel regions were examined with a Nitro-BT method staining. RESULTS: Immediately after the procedure, laser channels and surrounding injured myocardium could be stratified from the center to the border into 5 concentric zones, i.e., vaporized zone, carbonized zone, enzyme disappeared zone, enzyme-decreased zone and enzyme-concentrated zone. Two weeks later, the phenomenon disappeared. CONCLUSIONS: Immediately after transmyocardial revascularization, there is a ring of enzyme-concentrated zone at the outermost region of injured myocardium. Two weeks later, enzyme activities of reversibly injured myocytes appear to have recovered. PMID- 11780378 TI - Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism. AB - OBJECTIVE: To analyze heart rate variability (HRV) and its changes with thyroxine treatment in patients with hypothyroidism. METHODS: HRV was analyzed using 24 hour electrocardiographic recording in 38 patients with hypothyroidism and 21 normal controls. The changes in HRV were evaluated for the 18 hypothyroid patients after 3 months of thyroxine therapy. RESULTS: The time domain measurements of HRV in hypothyroid patients were much lower than those in the control group. As to HRV frequency domain, the high frequency power was significantly higher, but the ratio of low frequency power to frequency power for hypothyroid patients was lower than in the controls. These abnormal changes of HRV measurements in hypothyroid patients were improved after treatment with thyroxine and were associated with recovery of serum concentrations of FT3 and FT4. CONCLUSIONS: Patients with hypothyroidism often have autonomic neuropathies with a higher level of vagal tone. These abnormalities could be partly improved by thyoxine therapy. PMID- 11780379 TI - Activation of NF-kappa B in bronchial epithelial cells from children with asthma. AB - OBJECTIVES: To determine whether nuclear factor-kappa B (NF-kappa B) is activated in epithelial cells from children with asthma and to understand the role of NF kappa B in airway inflammation in asthma. METHODS: Bronchial mucosa specimens were obtained from 9 children with asthma and 6 control subjects. NF-kappa B expression in epithelial cells were detected by immunohistochemical examination, and NF-kappa B-DNA binding was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Nuclear expression of NF-kappa B in epithelial cells was observed in the 9 asthmatic children. NF-kappa B-DNA binding was found in 4 asthmatic children (EMSA was performed in 6 asthmatic children). In contrast, both nuclear expression and NF-kappa B-DNA binding were absent in the 6 control subjects. CONCLUSION: These results indicated that NF-kappa B is activated in epithelial cells from asthmatic children and the NF-kappa B activation may be the basis for the increased expression of many inflammatory genes and for airway inflammation in asthma. PMID- 11780380 TI - Effects of extrinsic positive end-expiratory pressure on cardiopulmonary function in patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: To choose one optimal extrinsic positive end-expiratory pressure (PEEPe) for ventilated patients with chronic obstructive pulmonary disease (COPD) and to compare two methods for choosing the optimal level of PEEPe. METHODS: Ten ventilated patients with COPD were included in the study. First, static intrinsic positive end-expiratory pressure (PEEPi, st) was measured when PEEPe was zero, and the PEEPi, st was called PEEPi, stz. PEEPe at 0%, 40%, 50%, 60%, 70%, 80%, 90% and 100% of PEEPi, stz, respectively, were applied randomly. Respiratory mechanics, hemodynamics, and oxygen dynamics were recorded 30 minutes after the level of PEEPe was changed. RESULTS: When PEEPe was not higher than 80% of PEEPi, stz, no measurement changed significantly. When PEEPe was increased to 90% and 100% of PEEPi, stz, PEEPi, st, peak inspiratory pressure, plateau pressure, pulmonary capillary wedge pressure and central venous pressure increased significantly, P < 0.01. Cardiac output and left ventricular work index decreased significantly, P < 0.01. Oxygen delivery decreased significantly, P < 0.05. When PEEPe was increased to 100% of PEEPi, stz, the right ventricular work index decreased significantly, P < 0.05. CONCLUSION: Eighty percent of PEEPi, stz was the upper limit of PEEPe. The results of the two methods used to set the level of PEEPe were identical. PMID- 11780382 TI - Th1/Th2 type cytokines in hepatitis B patients treated with interferon-alpha. AB - OBJECTIVE: To investigate the relationship between the expression of Th1/Th2 type cytokines and the effect of interferon-alpha therapy. METHODS: Th1/Th2 type cytokines were assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) on 23 patients with chronic hepatitis B who were treated with interferon-alpha. RESULTS: Levels of IFN-gamma in the supernatant of peripheral blood mononuclear cells (PBMC) cultures from the patients with hepatitis B were slightly lower than those of controls (P = 0.07). However, the levels of IL-4 were higher than those of controls (P = 0.01). Cytokines measurements during IFN-alpha treatment showed a trend to decreasing levels of IL-4 at 4, 12, and 24 weeks. Levels of IFN-gamma were slightly increased following IFN-alpha treatment (P = 0.09). In patients with a complete response to IFN-alpha, the levels of IFN-gamma were higher at 24 weeks following IFN-alpha treatment than that of pre-treatment (P = 0.04), and the levels of IL-4 decreased markedly at 12 and 24 weeks (P = 0.02, 0.03, respectively). mRNA expression positively correlated with the level of Th1/Th2 type cytokines in the supernatant. CONCLUSION: The expression of Th2 type cytokines is predominant in patients with chronic hepatitis B. Interferon-alpha therapy can modulate the balance of Th1/Th2 type cytokines, and this is related to its clinical effect. Levels of Th1/Th2 type cytokines could be a predictor of clinical response during Interferon-alpha treatment. PMID- 11780381 TI - Differentiation of NIH3T3 fibroblasts into adipocytes induced by peroxisome proliferator activated receptor gamma 2 expression. AB - OBJECTIVE: To express mouse peroxisome proliferator activated receptor gamma 2 (mPPAR gamma 2) in NIH3T3 fibroblasts mediated by the recombinant retrovirus and study its function. METHODS: The mPPAR gamma 2 gene was subcloned into retrovirus vector pGCEN to generate the recombinant pGCEN/mPPAR gamma 2. Then it was packaged into PA317 cells and selected with G418. Viral supernatants were harvested and then used to infect NIH3T3 fibroblasts. PPAR gamma activator 5, 8, 11, 14-eicosatetraynoic acid (ETYA) was used to induce the mPPAR gamma 2 expressing NIH3T3 cells into adipocyte differentiation. RESULTS: The recombinant retrovirus pGCEN/mPPAR gamma 2 was constructed, and the higher titers of the viral supernatants were obtained. mPPAR gamma 2 was expressed in NIH3T3 cells mediated by the recombinant retrovirus. Lipid accumulation obviously existed in these induced adipocytes which morphologically resembled mature adipocytes in vivo and expressed tissue specific adipocyte P2 (AP2) and Leptin genes. CONCLUSIONS: An adipocyte differentiation model in vitro was successfully established. The work is the basis for further research on the molecular mechanism of adipocyte differentiation induced by PPAR gamma 2. PMID- 11780383 TI - Expression characteristics of c-fos, c-myc and bFGF in early burn tissue. AB - OBJECTIVE: To investigate the sequence and characteristics of expression of proto oncogenes, c-fos, c-myc and endogenous basic fibroblast growth factor (bFGF), in burn tissue from rats. METHODS: A partial thickness burn of 30% TBSA was created on the backs of Wistar rats. Immunohistochemistry was used to detect the expression of these proteins in normal and burned skin at 3 hours, 6 hours, 1 day, 3 days, 7 days and 14 days postburn. RESULTS: Expression of c-fos, c-myc and bFGF was induced by the burn, but these three proteins showed different expression levels in sequence and distribution. Expression of c-fos increased and peaked at 3 hours postburn. Stain positive granules were distributed mainly in the cytoplasm of basal cells and the nuclei of fibroblasts. The expression of bFGF protein increased at 6 hours and peaked at 1 day postburn; it was distributed in the cytoplasm of fibroblasts. c-myc protein peaked at 3 days postburn and was also distributed in the cytoplasm of fibroblasts. CONCLUSIONS: Thermal injury can induce c-fos, c-myc and bFGF expression and show phasic control and regional distribution. The phasic expression of these three proteins indicates that there maybe a regulatory relationship between proto-oncogenes and growth factors in early burn. This may play an important role in late tissue repair. PMID- 11780384 TI - Reversing drug resistance in the ovarian carcinoma cell line SKOV3/mdr1 in vitro by antisense oligodeoxynucleotides. AB - OBJECTIVE: To investigate the effect of multidrug resistance gene 1 (mdr1) antisense oligodeoxynucleotides (ODNs) on reversing multidrug resistance in the drug resistant ovarian carcinoma cell line SKOV3/mdr1. METHODS: The ovarian carcinoma cell line SKOV3 transducted with a human multidrug resistance gene (mdr1) served as the drug resistant model (SKOV3/mdr1). The mdr1 antisense ODNs was transfected into SKOV3/mdr1 cells while mediated by lipofectamine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression and the amount of the mdr1 mRNA in the cells. The positive rate and function of the mdr1 gene product P-glycoprotein (Pgp) in the mdr1 antisense ODNs treated SKOV3/mdr1 cells were determined by flow cytometry and rhodamine 123 efflux. Drug resistance in the SKOV3/mdr1 cell line was observed by MTT assay and cell colony culture. RESULTS: The mdr1 mRNA level was decreased to about 60% of that of beta-actin after mdr1 antisense ODNs treatment. The Pgp positive rate of mdr1 antisense ODNs treated SKOV3/mdr1 cells decreased from 100% to 52.6% (P < 0.01). The intracellular rhodamine 123 retention was increased from 9.1% to 33.8% (P < 0.01). The chemoresistance to taxol decreased to 58% of SKOV3/mdr1 with mdr1 antisense ODN treatment. Compared with SKOV3/mdr1 cells in the control group, under a certain range of drug concentrations, the number of drug resistance colonies in mdr1 antisense ODNs treated SKOV3/mdr1 cells for taxol and doxorubicin decreased by 8.6 +/- 0.8 fold and 3.1 +/- 0.6 fold, respectively. Some non-specific functions during oligodeoxyncleotide treatment was also detected. CONCLUSION: mdr1 expression in the SKOV1/mdr1 cell line was partially inhibited after mdr1 antisense ODNs treatment at the mRNA and protein level, increasing the chemotherapy sensitivity of this drug resistant ovarian carcinoma cell line. PMID- 11780385 TI - Alleviation of hypoxic pulmonary vascular structural remodeling by L-arginine. AB - OBJECTIVE: To explore the effect of L-arginine on hypoxic pulmonary vascular structural remodeling and its possible mechanisms. METHODS: Eighteen Wistar rats were randomly divided into three groups: the hypoxia group, the hypoxia with L arginine group and the control group. Pulmonary artery mean pressure was evaluated with right cardiac catheterization. Pulmonary vascular structural changes were also observed. Plasma concentration of nitric oxide (NO) was measured via spectrophotometry, and endothelin-1 (ET-1) mRNA expression in pulmonary artery endothelial cells was detected using in situ hybridization. RESULTS: The pulmonary artery mean pressure was significantly high in hypoxic rats than in normal controls (20.33 +/- 2.18 mm Hg vs 15.38 +/- 1.05 mm Hg, P < 0.05). Microstructural and ultrastructural analysis revealed the development of hypoxic pulmonary vascular structural remodeling in the hypoxic rats. Meanwhile, the plasma NO concentration was markedly lower in the hypoxic rats than in controls (P < 0.05). The expression signals of ET-1 mRNA by pulmonary artery endothelial cells of hypoxic rats strengthened obviously. L-arginine ameliorated pulmonary hypertension (16.73 +/- 1.35 mm Hg vs 20.33 +/- 2.18 mm Hg, P < 0.05) as well as pulmonary vascular structural remodeling in the hypoxic rats in association with an increase in plasma NO concentration (P < 0.05) and inhibited ET-1 mRNA expression by the endothelial cells of pulmonary arteries. CONCLUSION: L-arginine might play an important role in the regulation of hypoxic pulmonary vascular structural remodeling and hypoxic pulmonary hypertension. The mechanism is probably related to promoting NO production and, as a result, inhibiting ET-1 mRNA expression by pulmonary artery endothelial cells in hypoxic rats. PMID- 11780386 TI - Computerized tomography pleurography: a new method for detecting minor pleural lesion. AB - OBJECTIVES: To evaluate the ability of CT pleurography (CTP) in detecting minor pleural lesions in patients with pleural effusion and to assess its value in distinguishing malignant from benign pleural lesions. METHODS: A prospective study of 50 patients with pleural effusion was conducted using conventional CT and CTP. CT scan was run after injecting an appropriate amount of contrast medium into the pleural cavity. RESULTS: In 24 patients, all lesions detected by conventional CT were demonstrated by CTP. In 13 of 24 patients, CT pleurography detected additional lesions. In 20 of 26 patients with negative findings on conventional CT, CTP was capable of demonstrating the presence of pleural lesions. The sensitivity, specificity and accuracy of detecting pleural lesions were 25%, 100% and 30% for conventional CT, 86%, 100% and 87% for CTP, respectively. CONCLUSION: CTP is superior to conventional CT in detecting and for the differential diagnosis benign and malignant pleural lesions. PMID- 11780387 TI - Treatment of hepatic failure with artificial liver support system. AB - OBJECTIVE: To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. METHODS: 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). RESULTS: 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. CONCLUSION: ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate. PMID- 11780388 TI - Isolation and cultivation of porcine hepatocytes for extracorporeal artificial liver support system. AB - OBJECTIVE: To develop procedures for the successful harvesting of large quantities of viable and functional pig liver cells from abattoir organs. METHODS: The procedure included partial liver lobe retrograde perfusion and mechanical/enzymatic digestion of the liver tissue, followed by separation of the hepatocytes, based on size and density, from contaminating cell types. RESULTS: Digestion of the partial liver lobe resulted in an average yield of 1.39 x 10(9) cells (9.9 x 10(8) cells/g liver) with an average viability of 92.5%. The yield and viability of cells were improved by dispase/collagenase resultant digestion. The emergence of blebby cells was blocked by supplying oxygen to the cell isolation buffers. Isolated hepatocytes seeded onto polystyrene surfaces remained viable and functional at a level comparable to that of rat hepatocytes, although their function decreased over time. CONCLUSIONS: Adult pig hepatocytes can be harvested with high yields and retain viability and differentiated function using this method. Abattoir pig livers can be an excellent source of hepatocytes for use as the biological component of artificial liver assist devices. PMID- 11780389 TI - Biological features of mesenchymal stem cells from human bone marrow. AB - OBJECTIVE: To study the biological characteristics of mesenchymal stem cells (MSCs) from human bone marrow. METHODS: A culture of mesenchymal stem cells was initiated from bone marrow low-density mononuclear cells separated by Percoll Centrifugation and maintained in low-glucose Dulbecco's modified Eagle's medium (DMEM) with 10% selected fetal calf serum. Cell growth pattern and its responses to cytokines were evaluated by trypan blue exclusion and MTT test, respectively. Cell cycle and surface antigenic features were analyzed by flow cytometry technique. Cytochemistry characteristics of MSCs were determined. RESULTS: Easy handling methods to isolate and culture expand MSCs were developed in this study. MSCs were unique in their phenotypes. They were positive for CD29, CD44, CD166, and negative for CD34, CD45, HLA-DR and Ulex europaeus. Cytochemistry evaluation showed that MSCs were homogeneously positive for acid alpha-naphthl acetate esterase (ANAE), glycogen (periodic acid Schiff reaction, PAS), and negative for acid phosphatase (ACP) and the Sudan black reaction (SB). Around 5% of them were positive for alkaline phosphatase (ALP). The cells had a population doubling time of 30 hours and cell cycle analysis showed that approximately 10% of them were in S phase. MSCs grew at significantly different rates when incubated in the presence of various recombinant human cytokines, of which interferon gamma, tumor necrosis factor alpha, stem cell factor and insulin-like growth factor promoted the proliferation of MSCs dramatically, while others tested had no effects on cell growth. CONCLUSIONS: MSCs are a homogenous population of cells that have unique growth, phenotypical and cytochemical characteristics. Furthermore, the diverse responses of MSCs to different cytokines provide a clue for the selection of optimal expansion and maintenance of MSCs. PMID- 11780390 TI - Association and contribution of ERK to IL-6-induced activation of signal transducer and activator of transcription in a human myeloma cell line. AB - OBJECTIVE: To investigate the regulation effect of protein kinase ERK on the activation of transcription factor STAT3 in response to IL-6 in the Sko-007 human myeloma cell line. METHODS: Electrophoretic mobility shift assay (EMSA) and immunoprecipitation (IP) were used to show the activation of STAT3 and ERK in Sko 007 cells in the presence and absence of IL-6. Antisense oligonucloetides of ERK (ERK-AS) were transfected into Sko-007 cells to specifically inhibit the expression and activity of ERK. The changes in the activation of STAT3 in the transfected cells were also exhibited by EMSA. Direct binding between STAT3 and ERK was analyzed by co-IP. RESULTS: Both STAT3 and ERK were activated in Sko-007 cells stimulated with IL-6. ERK-AS inhibited STAT3 activation by IL-6. Moreover, activated ERK could form a complex with STAT3 in Sko-007 cells. CONCLUSION: ERK can bind STAT3 directly and be required for its maximal activation in Sko-007 cells stimulated by IL-6. PMID- 11780391 TI - Growth inhibition of gastric cancer cells by all-trans retinoic acid through arresting cell cycle progression. AB - OBJECTIVE: To investigate the mechanism of all-trans retinoic acid (ATRA) on the regulation of the cell cycle in gastric cancer cells. METHODS: The protein level was detected by Western blot. Immunoprecipitation was used in protein kinase activity determination. Cell growth and cell cycle phase were examined by MTT assay and flow-cytometric analysis, respectively. RESULTS: ATRA could effectively induce G0/G1 arrest and inhibit cell growth in certain human gastric cancer cell lines. ATRA might induce p21WAF1/CIP1 expression in ATRA-sensitive cell lines through p53-dependent and p53-independent pathways. Induction of p21WAF1/CIP1 caused decrease in CDK4 and CDK2 activities independent of CDK4 and CDK2 protein expression levels. In addition, the dephosphorylated form of Rb protein increased because of the down-regulation of CDK4 and CDK2 activities by ATRA. CONCLUSIONS: Growth inhibition on gastric cancer cells by ATRA occurs through the regulation of relevant proteins leading to the arrest of cell cycle progression. PMID- 11780392 TI - Monoclonal anti-idiotype antibody bearing the internal image of nasopharyngeal carcinoma associated antigen. AB - OBJECTIVE: To generate and characterize anti-idiotypic monoclonal antibody (Ab2) that bears the internal image of nasopharyngeal carcinoma (NPC) associated antigen. METHODS: Using NPC monoclonal antibody (Ab1) as immunogen, hybridoma cells were obtained by fusion of SP2/0 myeloma cells with immunized murine spleen cells. Positive clones were screened by Sandwich ELISA and a binding inhibition test. To determine whether Ab2 possess the internal image of the original antigen or not, mice were immunized with Ab2. ELISA and the competitive inhibition assay tested anti-anti-idiotypic antibodies (Ab3) in anti-sera. Cell-mediated immunity to tumors induced by Ab2 was investigated by a delayed-type hypersensitivity response and the mouse T-cell proliferation assay. RESULTS: Anti-idiotypic monoclonal antibodies against the monoclonal anti-NPC antibodies FC2 and HNL5 were generated that recognize NPC associated antigens. These Ab2, which were designated 2H4 and 5D3, could inhibit the binding of FC2 or HNL5 to NPC cell lines. Anti-sera from the immunized mice, which contained Ab3, could compete with FC2 or HNL5 for binding with NPC cell by a competitive inhibition assay. Mice immunized with 2H4 or 5D3 coupled with keyhole limpet hemocyanin (KLH), showed a positive and specific delayed-type hypersensitivity (DTH) reaction after stimulation by NPC cells. The mouse T cell proliferative assay indicated that there was a significantly higher proliferative response of the splenocytes in the experimental groups than that in control groups. CONCLUSIONS: Anti-idiotypic antibodies 2H4 and 5D3 are Ab2 beta bearing the internal image of the epitope of NPC associated antigen. Either 2H4 or 5D3 expressing three-dimensional shapes that resemble the structure of natural antigens could induce humoral and cellular immune response. PMID- 11780393 TI - Cell cycle analysis by cyclin E + A/DNA multiparameter flow cytometry in exponential growth MOLT-4 cells. AB - OBJECTIVE: To establish a new method for analyzing the cell cycle in tumor which is a kind of cell cycle disease. METHODS: Mixtures of cyclin E and cyclin A antibodies were incubated with fixed MOLT-4 cells, and measured by flow cytometry. RESULTS: We developed a cyclin E + A/DNA flow cytometry analysis method, which may distinguish G0, early G1, late G1, S, G2 and M phase cells, rather than three phases in the DNA content histogram. CONCLUSION: Cyclin E + A/DNA multiparameter flow cytometry can simultaneously differentiate in the same sample six cell groups: G0, early G1, late G1, S, G2 and M phase cells. It performed better than any other cell cycle analysis methods that we have used and has a definite cell biology foundation. PMID- 11780394 TI - Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit. AB - OBJECTIVE: To investigate the efficiency of the cytosine deaminase adenoviral/5 fluorocytosine system on prostate cancer cell lines. METHODS: We used cell culture, infectivity and sensitivity tests, to observe bystander effect by animal tests. RESULTS: Established prostate cancer cell lines are eventually infectible by adenoviral vector. The ratio of vector/cell at which infection occurs depends on the specific cell line. The peak of expression of the transferred cytosine deaminase gene occurred in cells at different time, but persisted beyond 11 days. These prostate cell lines are sensitized to 5-fluorocytosine by infection with adenoviral vector carrying the cytosine deaminase gene. Only 5% of the LNCap and 10% of the RM-1 cells were infected and produced 100% cell death. In the animal test, there was significant inhibition of tumor growth at a ratio of 400 vector particles/cell with the systematic treatment of 5-fluorocytosine. CONCLUSIONS: Adenoviral vector carrying a cytosine deaminase transcription unit can sensitize prostate cancer cell lines to 5-fluorocytosine. The system can significantly inhibit the growth of prostatic tumors in mice. PMID- 11780395 TI - Molecular basis for the effect of lipid lowering drugs on growth factors after de endothelialization. AB - OBJECTIVE: To study the mechanism and effect of lipid lowering drugs in arresting the development of arterial restenosis after angioplasty. METHODS: De endothelialization injury of rabbit aortae, common iliac and femoral arteries using balloon angioplasty and the expression of growth factors such as platelet derived growth factor-B (PDGF-B), transforming growth factor beta-1 (TGF beta-1), and fibroblast growth factors (bFGF) were investigated. Total serum cholesterol (TC) and triglycerides (TG) were analyzed during and after the treatment using either simvastatin combined with gemfibrozil or simvastatin alone for 6 weeks. RESULTS: Serum total cholesterol and triglycerides were only slightly to moderately increased after high cholesterol ration intake lasting for 6 weeks in rabbits of two therapeutic groups (simvastatin plus gemfibrozil or only simvastatin). A positive correlation was found between TC and intimal/medial ratio (r = 0.5873, P < 0.05). PDGF-B detected by immuno-histochemistry and RT-PCR analysis showed that the release of PDGF-B was inhibited by simvastatin and gemfibrozil after de-endothelialization. RT-PCR analysis showed that TGF beta-1 was increased in the neointima in two treatment groups but no definite change was seen in the mRNA of bFGF in the smooth muscle cell (SMC) of the balloon-injured arteries even under lipid lowering drug treatment. CONCLUSION: In addition to the lipid lowering effect, both simvastatin and gemfibrozil also influence the release of PDGF-Band TGF-1 in the neointima after de-endothelialization. PMID- 11780396 TI - Apolipoprotein E polymorphism in the early onset of coronary heart disease. AB - OBJECTIVE: To assess the relationship between apolipoprotein E (apoE) polymorphism and the early onset of coronary heart disease (CHD) and the effect of apoE on lipids and lipoproteins in healthy Chinese subjects. METHODS: Sixty eight patients with CHD younger than 55 years (CHD1), 136 patients with CHD older than 65 years (CHD2), and 136 healthy subjects were enrolled, and their plasma levels of triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were determined. The apoE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: apoE 3/4 genotype and E4 allele frequency in the CHD1 group were higher than those in the CHD2 group and healthy subjects, while no differences were found between CHD2 and healthy subjects. Meanwhile, the plasma levels of TC and low density lipoprotein cholesterol (LDL-C) were higher in the CHD2 group than in both CHD1 group and healthy subjects. Each apoE isoprotein has variable TC and LDL-C levels that is E2 (E2/2 + E2/3) < E3(E3/3) < E4(E4/4 + E3/4). CONCLUSION: apoE is one of the genetic factors that affect TC and LDL-C levels, and apoE 4 has a very close relation to CHD, suggesting that apoE 4 is an independent genetic factor of the early onset of CHD. PMID- 11780397 TI - Influence of growth hormone-insulin-like growth factor I axis on normal pregnancy. AB - OBJECTIVE: To investigate the role of growth hormone-insulin-like growth factor I (IGF-I) axis in normal pregnancy. METHODS: Totally, 116 normal pregnant women were recruited from January 1997 to June 1998, with 20 normal nonpregnant women as controls. Maternal growth hormone (GH) and IGF-I concentrations were assayed by RIA and enzyme-linked immunosorbent assay, respectively. RESULTS: Maternal serum levels of GH increased throughout gestation, reached a peak at 25 weeks of pregnancy and remained fairly high (chi 2 = 40.458, P < 0.0001). There was a significant difference between samples at 5-9 week gestational age and the controls (3.45 micrograms/L vs 1.61 micrograms/L, P < 0.05). The maternal serum levels of IGF-I increased rapidly throughout gestation from 29-week gestation and reached a peak of 188.86 micrograms/L at term delivery (chi 2 = 50.224, P < 0.0001). CONCLUSIONS: Maternal GH levels increased progressively throughout gestation, which correlated with fetal growth. Maternal GH may regulate nutrition supply among mother, placenta and the fetus and play an important role in transporting nutritional substrates by the placenta. The maternal IGF-I in the third trimester may promote fetal growth and placental functions. PMID- 11780398 TI - Ultrastructure of intrahepatic biliary canaliculi and prognosis of congenital biliary atresia. AB - OBJECTIVE: To investigate the relationship between the ultrastructure of intrahepatic biliary canaliculi and the prognosis of congenital biliary atresia. METHODS: Liver biopsies from 25 patients who were operated on for congenital biliary atresia were examined under the transmission electron microscope. The relationship between the number of well-developed bile canaliculi and patient prognosis was studied. RESULTS: The survival rate for 13 patients with well developed intrahepatic biliary canaliculi and 12 patients with poorly-developed intrahepatic biliary canaliculi were 92.3% (12/13) and 33.3% (4/12) respectively. The difference between two groups was statistically significant (P < 0.05). CONCLUSIONS: Intrahepatic biliary canaliculi ultrastructure could be used as one of the prognostic factors in congenital biliary atresia. PMID- 11780399 TI - Mucinous adenocarcinoma originating in localized type adenomyomatosis of the gallbladder. PMID- 11780400 TI - The present and future of interventional catheterization for congenital heart disease. PMID- 11780401 TI - Percutaneous balloon aortic valvuloplasty in the treatment of congenital valvular aortic stenosis in children. AB - OBJECTIVE: To assess the effect of the balloon valvuloplasty for for congenital valvular aortic stenosis (AS) in children. METHODS: A total of 27 (mean age 6.09 years) children with AS accepted the treatment of percutaneous balloon aortic valvuloplasty (PBAV). The ratios of balloon/valve were 0.95 +/- 0.08 for 19 cases of typical AS and 1.00 +/- 0.11 for 8 cases of hypoplastic AS. The patients were evaluated by the gradients across aortic valves in pre- and post-PBAV and by echocardiogram during the follow-up period. RESULTS: Fifteen of 19 (78.9%) cases of typical AS had a better outcome and the gradient of the remaining 4 cases (26.7%) had increased after follow-up (delta P > 50 mm Hg). Four of 8 (50.0%) cases of hypoplastic AS had satisfactory responses and the gradient of the remaining 3 cases (75.0%) rose. There was no moderate to severe aortic insufficiency (AI). CONCLUSION: The balloon aortic valvuloplasty provides safe and significant hemodynamic and clinical improvement in pediatric patients. The outcome of PBAV for typical AS is better than for hypoplastic AS. PMID- 11780402 TI - Transcatheter closure in 354 pediatric cases of patent ductus arteriosus using five different devices. AB - OBJECTIVE: To assess the effect of transcatheter closure of patent ductus arteriosus (PDA) by comparing five different devices. METHODS: 354 patients (135 males, 219 females) underwent transcatheter closure of PDA using the Porstmann Ivalon plug, Rashkind double umbrella, Sideris button device, Coils and Amplatzer occluders. The mean PDA diameter at its narrowest segment was 3.1 +/- 1.3 mm. Qp/Qs was 2.2 +/- 0.5. Follow-up evaluation was performed with color flow mapping of the main pulmonary artery at 24 h and 6 months after closure. RESULTS: Successful occlusion was observed in 92% (23/25) for the Porstmann device, 98.7% (77/78) for the Rashkind device, 100% (43/43) for the Sideris device, 100% (69/69) for the Coil and 100% (139/139) for the Amplatzer device. No residual shunts were needed for the Porstmann, while 1.4%-15% of patients who received the Rashkind, Sideris, Coils or Amplatzer needed residual shunts during follow-up. There were complications of 24% (6/25) for the Porstmann, 3.8% (3/78) for the Rashkind, 1.4% (1/69) for Coils and 1.4% (2/139) for the Amplatzer. No complications were found in patients with the Sideris device. CONCLUSION: The results showed that the Sideris device, Coils and the Amplatzer device are more effective and safer than the others for the occlusion of PDA in children. PMID- 11780403 TI - Percutaneous balloon angioplasty of coarctation of the aorta in children: 12-year follow-up results. AB - OBJECTIVE: To evaluate the efficiency of percutaneous balloon angioplasty of coarctation of the aorta in children and discuss its risk factors that can lead to poor long-term results. METHODS: From September 1987 to August 1999, 24 patients underwent 27 balloon angioplasty procedures for native or recurrent coarctation of the aorta at our institution. There were 19 patients with discrete (membranous) coarctation, 4 patients with long-segment and aortic arch hypoplasia, and 1 patient with postoperative recurrence. The balloon diameter was chosen not to exceed the diameter of the aorta proximal to the stenotic site (11.06 +/- 2.80 mm vs 11.78 +/- 3.18 mm), with the chosen diameter two to four times that of the stenotic segment (2.57 +/- 0.68 times). The patients have been followed up for half to twelve years (mean 6.2 +/- 2.8 years). Satisfactory result was defined as a reduction in the pressure gradient across the site of coarctation to < or = 20 mm Hg. RESULTS: The systolic pressure gradient across the coarctation site decreased from 48.17 +/- 14.68 mm Hg to 14.96 +/- 13.12 mm Hg (P < 0.01) and the diameter of the coarctation site increased from 4.66 +/- 2.43 mm to 8.80 +/- 3.32 mm (P < 0.01). Immediate satisfactory results were obtained in 19 patients (79%). Of the 5 patients with unsatisfactory results, 4 had aortic arch hypoplasia and 1 had membranous coarctation. Of the 19 patients with satisfactory results, 18 patients had membranous coarctation and 1 patient had recurrent postoperative coarctation. No aneurysm and other complications had occurred in any patients at the follow-ups. CONCLUSION: Percutaneous balloon angioplasty is an effective treatment alternative to surgery in most patients with recurrent postoperative or native membranous coarctation of the aorta. It should not be recommended for the coarctation of aortic arch hypoplasia. PMID- 11780404 TI - All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline. AB - OBJECTIVE: To determine whether all-trans retinoic acid (atRA) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline. METHODS: All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Monocrotaline-injected rats received either atRA (30 mg.kg-1.day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromometry, respectively. RESULTS: The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7 +/- 4.3 mm Hg vs 15.1 +/- 1.5 mm Hg and 38.5 +/- 6.4 mm Hg vs 16.4 +/- 2.0 mm Hg, P < 0.01). MMP-1 mRNA overexpression was present on Day 14 (0.72 +/- 0.15 vs 0.39 +/- 0.08, P < 0.01) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 +/- 1.13 micrograms/mg vs 5.10 +/- 0.91 micrograms/mg, P < 0.05) and increased significantly on Days 21 and 28 compared with the control. atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 +/- 0.70 micrograms/mg vs 7.96 +/ 1.13 micrograms/mg and 7.77 +/- 0.96 micrograms/mg vs 9.93 +/- 1.27 micrograms/mg, P < 0.01) and the mean pulmonary artery pressure compared with the model group (19.6 +/- 3.2 mm Hg vs 25.7 +/- 4.3 mm Hg and 26.3 +/- 4.6 mm Hg vs 38.5 +/- 6.4 mm Hg, P < 0.01). CONCLUSION: atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline. PMID- 11780405 TI - Evaluation of coronary artery bypass graft patency using three-dimensional reconstruction and flow study of electron beam tomography. AB - OBJECTIVE: To establish and evaluate two protocols for the noninvasive visualization and assessment of coronary artery bypass graft (CABG) patency on electron beam tomography (EBT). METHODS: Two hundred and fourteen consecutive patients who underwent coronary artery bypass graft surgery were scanned using both EBT angiography with 3-dimensional reconstruction and EBT flow study with time-density-curve analysis. RESULTS: There were 589 CABGs evaluated in this study (10 grafts were excluded because of artifacts). Among them, 133 (98.5%) of 135 arterial grafts were patent, and 345 (77.7%) of 444 saphenous-vein grafts were patent. Within 5 years or between 5 and 10 years after operation, arterial graft patency exceeded venous graft patency (P < 0.001). Three-dimensional EBT angiography achieved higher sensitivity, specificity and accuracy (97.7%, 94.1% and 96.7%, respectively) than did EBT flow study (88.4%, 82.4% and 85.2%, respectively) for evaluating occlusion or patency of CABG. The intra-graft flow of patent arterial and venous grafts were 4.9 +/- 2.2 ml.min-1.g-1 and 6.9 +/- 2.8 ml.min-1.g-1, respectively (P < 0.001). CONCLUSION: The combination of EBT three-dimensional reconstruction and flow study can be more effective in the assessment of CABG anatomy and quantification of patent CABG blood flow. PMID- 11780406 TI - Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome. AB - OBJECTIVE: To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene. METHODS: Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23-32, where the mutational hotspots for severe forms of Marfan syndrome are located. RESULTS: Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation. CONCLUSION: Taking advantage of the clustering phenomenon of mutations in severe forms of marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots, thus reducing the effort that would otherwise be much greater because of the size of the gene. PMID- 11780407 TI - Gene expression of glucose transporters and its regulation by glucose in mesothelial cells. AB - OBJECTIVE: To observe the influence of glucose on the expression of glucose transporters (GluTs) in peritoneal tissues. METHODS: Mesothelial cells (MsCs) from Sprague-Dawley (SD) rats were cultured in medium with glucose 214.4 mmol/L or 75.5 mmol/L. The normal medium with glucose 17.5 mmol/L was used as control. Total RNA was extracted from each sample after 24 hours incubation. Reverse transcript polymerase chain reaction (RT-PCR) was performed with primers corresponding to sodium-glucose transporter (SGIT1) and GluT1-GluT4. mRNA expression of the above GluTs from each sample was measured with quantitative PCR. RESULTS: GluT1 and GluT2 mRNA can be detected in MsCs from SD rats, while no positive bands can be found specifically for GluT3, GluT4 and SGiT1. Quantitating the amount of PCR products indicated that the levels of GluT1 mRNA in MsCs cultured 24 h in both 214.4 mmol/L glucose and 75.5 mmol/L glucose medium decreased dramatically compared with that in normal medium (P < or = 0.01). While under the same conditions, the levels of GluT2 mRNA in MsCs cultured 24 h in 214.4 mmol/L and 75.5 mmol/L glucose medium both increased significantly (P < 0.01). CONCLUSIONS: GluT1 is strongly expressed in MsCs under normal glucose levels and decreased dramatically under high glucose conditions, while GluT2 expressed at a low level in normal medium and increased greatly after incubation in high glucose conditions. This may play a great role in glucose absorption during peritoneal dialysis and have some connection with ultrafiltration failure due to the alteration of glucose absorption after long-term dialysis. PMID- 11780408 TI - Expression and function of c-kit receptor in bone marrow mononuclear cells of patients with myelodysplastic syndromes. AB - OBJECTIVE: To determine the expression and function of the c-kit receptor in bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndromes (MDS). METHODS: Direct immunofluorescence assay and reverse transcriptase polymerase chain reaction (RT-PCR) were used to detect c-kit protein and c-kit mRNA expressions in the BMMNC of 29 MDS patients and 10 normal controls. Cell culture was used to detect the function of the c-kit receptor. RESULTS: c-kit protein expression in the MDS group was significantly higher than that in the control group (8.58% +/- 5.28% vs 3.04% +/- 1.49%, P < 0.05). c-kit protein expression in the refractory anemia (RA) group was significantly lower than that in the RA with an excess of blasts (RAEB)/RAEB in transformation (RAEB-t) group (5.12% +/- 2.13% vs 10.01% +/- 5.07%, P < 0.05). The rate of c-kit protein expression was 32.43% in acute myeloblastic leukemia (AML) cases transformed from MDS (t-AML). c-kit mRNA expression in the MDS group was correlated with c-kit protein expression. Interleukin-3 (IL-3) and erythropoietin (Epo), with or without stem cell factor (SCF), upregulated c-kit protein and its mRNA expression. In the presence of IL-3 and Epo, SCF showed significant stimulating effects on the formation of CFU-GM and BFU-E in semi-solid cultures of normal BMMNC, but had no effects on those of the MDS patients. CONCLUSION: The protein and mRNA expression of the c-kit receptor in the BMMNC of MDS patients were higher than those of normal controls, and the function of this receptor in MDS BMMNC was abnormal. PMID- 11780409 TI - Erythrocyte membrane protein abnormalities in beta-thalassemia of the Li nationality in Hainan. AB - OBJECTIVE: To determine the composition of abnormal red cell membrane skeleton. METHODS: By sodium dodecyl sulphate polyacrylamide gel electrophoresis of ghostcorpuscles, we quantified the amount of protein by densitometric evaluation. RESULTS: The results showed that in beta-thalassemia, the amount of spectrin, 4.5 protein and globin significantly increased compared with the controls (26.05 +/- 1.46, 21.69 +/- 1.86; 22.87 +/- 5.61, 12.99 +/- 2.33; 15.23 +/- 3.31 and 4.97 +/- 2.73, respectively, P < 0.05). CONCLUSION: These data suggest that the erythrocyte membrane protein composition matched with globin in patients with beta-thalassemia of the racial Li minority are different from the normal control. These factors increase rigidity but decrease deformability of the beta thalassemic red cell membrane, which may lead to hemolytic anemia. PMID- 11780410 TI - Stable clonal expansion of the T-cell receptor V beta 6, V beta 17 and V beta 19 T cells in a cGVHD case using genescan analysis. AB - OBJECTIVE: To investigate the distribution and clonality of the T-cell receptor (TCR) V beta repertoire in chronic graft versus host disease (cGVHD). METHODS: The complementarity determining region 3 (CDR3) of the TCR beta gene with 24 variable regions was amplified in peripheral blood mononuclear cells drawn from one cGVHD patient after allogenic bone marrow transplantation (allo-BMT) 35, 39, 43 or 45 months respectively, using RT-PCR, to observe the expression of TCR V beta repertoire T cells. The PCR products were further analyzed by genescan to evaluate clonality of T cells. RESULTS: Fourteen or 16 TCR V beta subfamily T cells were detected in each sample of cGVHD case. Oligoclonal T cells were identified in TCR V beta 6, 16, 17, 19 and 21 subfamilies. The stable clonal T cells in all samples were identified in V beta 6, V beta 17 and V beta 21 subfamilies. CONCLUSION: Skewing distribution and stable clonal expansion of T cells can be found in cGVHD cases and it may be related to the initiation of cGVHD. PMID- 11780411 TI - Allogeneic peripheral blood stem cell transplantation for leukemia. AB - OBJECTIVE: To observe engraftment kinetics, the incidence and severity of graft versus-host disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: From June 1997 to May 1999, forty leukemia patients with a median age of 35 years underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 micrograms/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0-16.8) x 10(6) CD34+ cells/kg was infused into the recipients. Busulfan-cyclophosphamide (BU-CY) was used as the conditioning regimen. All patients received cyclosporine A and either methotrexate (n = 34) or methylprednisolone (n = 6) for GVHD prophylaxis. RESULTS: Engraftment of neutrophils and platelets was achieved at a median of 13 days (9-28 days) and 12 days (7-60 days) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5%), with grade II-IV acute GVHD in 10 patients (25%). Chronic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients (21/30, 70%) with a median follow up of 380 days (180-900 days). Transplant related mortality was 17.5% and the relapse rate was 10%. The probability of leukemia free survival at 3 years was 72.5%. CONCLUSION: Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD. PMID- 11780412 TI - Retroviral vector containing human p16 gene and its inhibitory effect on Bcap-37 breast cancer cells. AB - OBJECTIVE: To study the effects of the p16 gene on tumor cell growth inhibition and cell cycle arrest. METHODS: The recombinant retroviral vector pLp16SN was constructed by cloning the human p16 cDNA into the retroviral vector pLXSN. Retroviruses with or without the p16 gene were obtained by transfecting pLp16SN and pLXSN vectors into PA317 cells. Bcap-37 human breast cancer cells were infected with these retroviruses followed by selection with G418. The expression of p16 was detected by Northern and Western blots. Cell biological characteristics, including cell growth rate, cell cycle and tumorigenesis in nude mice were assessed. RESULTS: Both mRNA and protein expression of p16 in Bcap-37 cells transfected with retroviral vector containing the p16 gene were much higher than that in Bcap-37 cells transfected with empty vector or parental Bcap-37 cells. Cell overexpressing the p16 gene exhibited a slower rate of growth, a higher percentage of cells in the G1 phase, and smaller tumors in nude mice, compared with parental Bcap-37 cells and cells transfected with empty vector. CONCLUSION: Overexpression of the p16 gene could suppress the growth of Bcap-37 breast cancer cells by arresting the cell cycle at the G1 to S-phase. PMID- 11780413 TI - Apoptosis of renal tubular cells in congenital hydronephrosis. AB - OBJECTIVE: To assess apoptosis in congenital hydronephrosis and discuss its clinical significance. METHODS: Apoptosis was detected in 15 kidneys from children with congenital hydronephrosis (5 mild hydronephrosis, 5 moderate hydronephrosis and 5 severe hydronephrosis) using the electronmicroscope, in situ gap labeling of fragmented nuclear DNA and DNA fragmentation analysis. RESULTS: Apoptosis was seen in kidneys from children with congenital hydronephrosis. Margination of nuclear chromatin was identified and rounded apoptotic bodies were seen. The mean apoptotic index was 0.0941 +/- 0.017 in severe hydronephrosis, 0.0325 +/- 0.0169 in moderate hydronephrosis, and 0.0021 +/- 0.0031 in mild hydronephrosis. There was a significant difference between severe and moderate hydronephrosis (P = 0.0005), as well as between moderate and mild hydronephrosis (P = 0.0154). Moreover, with an increasing degree of hydronephrosis, the number of apoptotic cells also increased. Five kidneys with severe hydronephrosis and one kidney with moderate hydronephrosis showed typical apoptotic bands. CONCLUSION: Apoptosis might participate in damaging kidneys in children with congenital hydronephrosis. PMID- 11780414 TI - Characteristics, diagnosis and treatment of hepatic metastasis of pure immature ovarian teratoma. AB - OBJECTIVE: To analyze the characteristics of hepatic metastasis of pure immature ovarian teratoma and explore its proper diagnosis and treatment. METHODS: Eighteen cases of hepatic metastasis of pure immature ovarian teratoma were included in this study. The clinical stage, operation, chemotherapy and histopathology of primary and secondary tumors as well as the data from long term follow-ups were analyzed retrospectively. RESULTS: All of the hepatic metastatic tumors were located on the surface of the liver. 61.1% (11/18) of them were clinical stage III and 44.4% (8/18) were grade 1 at first operation. The hepatic metastatic rate was 16.7% (3/18) in the standard adjuvant chemotherapy group but increased markedly to 31.2% (15/48) in the irregular chemotherapy group. Auxiliary diagnostic methods could not indicate the correct results. The surgical resection rate of hepatic metastasis of pure immature ovarian teratoma was 94.4% (17/18). There were less complications in the group with tumor diameter less than 15 cm. The follow-up time ranged from 3 to 205 months with a mean of 20.9 months. The 3-year-survival rate was 77.8% (14/18), and mortality rate was 22.2%. The 5- and 10-year-survival rate was 55.6% (10/18) and 38.9% (7/18), respectively. The rate of loss in follow-up was 22.2% (4/18) and 38.9% (7/18), respectively, and one patient has survived for more than 17 years. CONCLUSIONS: The hepatic metastatic rate of pure immature ovarian teratoma could be decreased using standard adjuvant chemotherapy. Suitable surgical treatment could reduce complications and improve the prognosis for patients. PMID- 11780415 TI - Investigation of infection risk and the value of urine endotoxin during extracorporeal shock wave lithotripsy. AB - OBJECTIVE: To clarify the infection risks and the value of endotoxin determination in urine during extracorporeal shock wave lithotripsy (ESWL). METHODS: According to the distribution and complications of upper urinary calculi, 164 patients were divided into five groups. Group A consisted of 48 patients with 1 to 4 renal calculi, which were or less than 2 cm in diameter. Group B was composed of 24 patients with renal calculus larger than 2 cm in diameter or one to multiple renal calculi. Group C was composed of 22 patients with 1 to 3 renal calculi accompanied by 1 to 2 ureteric calculi. Group D consisted of 51 patients with 1 to 3 ureteric calculi that were 0.5 to 1.2 cm in diameter, respectively. Group E included 19 patients with complicated renal calculus, such as casting and staghorn renal calculus. Urine and blood samples of these patients were obtained before and after ESWL, respectively. Their urine samples were proven sterile prior to treatment. All samples were cultured for bacteria and investigated for endotoxin concentration by the limulus lysate test. RESULTS: No significant difference in serum endotoxin was noted before and after ESWL. Blood bacterial cultures were all negative in all patients after ESWL, similar to those before ESWL. Significant increases in urine endotoxin after ESWL compared with that before ESWL in patients of Groups B, C and E were observed, respectively (P < 0.05). There was no significant difference in urine endotoxin after ESWL compared with that before ESWL in patients of Groups A and D. The positive incidences of urine bacterial culture were significantly increased (P < 0.05) in Groups B and C and very significantly increased (P < 0.01) in Group E compared with those in Groups A and D. CONCLUSIONS: Urinary infection risk following ESWL was lower in patients with one to several renal calculi, which were less than 2 cm in diameter and did not interfere obviously with the urine flow or in patients with 1 to 3 ureteric calculi that were 0.5 to 1.2 cm in diameter. The risk was higher in those with complicated calculi, such as casting, staghorn renal calculus, renal calculus larger than 2 cm in diameter or renal calculi accompanied by ureteric calculi. For patients with higher infection risk after ESWL, prophylactic antibiotics are necessary even if bacteriuria is not present before ESWL. Endotoxin determination in urine is a reliable, sensitive and simple method for the diagnosis of bacterial infection in patients undergoing ESWL. PMID- 11780416 TI - Gynecological procedures under gasless laparoscopy. AB - OBJECTIVE: To evaluate gasless laparoscopy in treating gynecological conditions. METHODS: With Kirschner wire lifting, transversely or longitudinally introduced into abdominal wall subcutaneously, we exposed the operative field and pelvic organs with routine operative instruments under epidural anesthesia. When a dense pelvic adhesion was confronted, we used the temporarily low-pressured pneumolaparoscopy to dissect it. RESULTS: All procedures were carried out without organ injury, hematoma, or other complications. The operative field can be clearly seen with this method. The mean time for appendagectomy was one hour and for laparoscopic assisted vaginal hysterectomy 80 minutes. CONCLUSION: Gasless laparoscopy avoids the complications which occur in the routine laparoscopy such as subcutaneous or mediastinal pneumatoma, hypercarbonemia, air embolism, cardiopulmonary dysfunction. Our lifting method is simple, convenient, time and money saving, as well as more flexible for treating gynecological conditions. PMID- 11780417 TI - Vascular endothelial growth factor mRNA and its protein expression in decidua after terminating early pregnancy by mifepristone plus misoprostol. AB - OBJECTIVE: To investigate the action of mifepristone plus misoprostol on decidua at the level of vascular endothelial growth factor (VEGF) mRNA and its protein expression, as well as the mechanism of prolonged uterine hemorrhage after terminating early pregnancy with these drugs. METHODS: Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 weeks' duration, in which 15 women were treated with mifepristone and 15 were given mifepristone plus misoprostol. Enzyme-linked immunosorbant assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect VEGF protein and mRNA levels in decidua. RESULTS: In all three groups, only the VEGF121 amplification product of 452 bp was visualized. The mRNA and protein levels of VEGF showed no significant differences among the three groups (P > 0.05). CONCLUSION: In humans, early decidua VEGF121 mRNA is the main isoform. The action of mifepristone plus misoprostol on blood vessels in human decidua may be medicated by some factors other than VEGF. PMID- 11780418 TI - Relationship between c-fos gene expression and delayed neuronal death in rat neonatal hippocampus following hypoxic-ischemic insult. AB - OBJECTIVE: To explore the mechanism of perinatal hypoxia-ischemia encephalopathy, we studied the expression of the c-fos gene and its relationship with delayed neuronal death in a rat model. METHODS: Cerebral hypoxia-ischemia was produced in 7-day-old SD rats using the Rice model. Reverse transcription PCR (RT-PCR), immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of c-fos gene and cell apoptosis in the hippocampus. RESULTS: The selective expression of c-fos and delayed cell apoptosis were observed in the hypoxia-ischemia hippocampus. Expression of the c-fos gene was seen in the CA4 and cingulate sulcus neurons, and apoptosis was observed in the CA1 neurons. CONCLUSION: Transient expression of the c-fos gene may induce cerebral cell apoptosis, and may have complex relations with delayed cell death. PMID- 11780419 TI - Optical coherence tomography in measuring retinal nerve fiber layer thickness in normal subjects and patients with open-angle glaucoma. AB - OBJECTIVES: To investigate image characteristics and thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes using optical coherence tomography (OCT), and analyze the relationship between RNFL thickness and visual field index. METHODS: Eighty-three normal persons (150 eyes) and 83 patients with primary open angle glaucoma (POAG, 149 eyes) underwent OCT examinations with 3.4 mm diameter circle scan to calculate the RNFL thickness. Statistical analysis was used to compare differences in RNFL thickness in quadrants and means between the normal and glaucomatous groups and the different stages of POAG. Linear correlation and regression analysis were used to show the correlation between RNFL thickness and visual field index of 115 eyes in glaucomatous patients. Reproducibility, sensitivity and specificity of RNFL measurements using OCT were evaluated. RESULTS: RNFL thickness measured by OCT in normal subjects was thicker in superior and inferior, less in temporal, and thinnest in nasal quadrants. The curve showed double peaks. RNFL of glaucomatous patients showed local thinning or defect, diffuse thinning, or both. The mean RNFL thicknesses of the normal group in the temporal, superior, nasal and infelor quadrants were 90.1 +/- 10.8 microns, 140.4 +/- 10.5 microns, 85.2 +/- 14.0 microns, and 140.4 +/- 9.7 microns, respectively with a mean of 114.2 +/- 6.0 microns. The numbers for the glaucomatous group were respectively 56.0 +/- 31.0 microns, 81.0 +/- 36.3 microns, 47.1 +/- 27.5 microns, and 73.4 +/- 38.4 microns for the four quadrants, with a mean of 64.6 +/- 28.8 microns. There was a significant difference in RNFL thickness between the normal and glaucomatous groups (P < 0.000), and the three stages (early, developing and late) of glaucomatous groups (P < 0.000). There was a close negative relationship between RNFL thickness and visual field index (r = 0.796, P < 0.0001). The sensitivity and specificity of RNFL thickness in POAG measured using OCT were 93.3% and 92.0%, respectively. CONCLUSIONS: OCT can quantitatively measure RNFL thickness differences between normal persons and glaucomatous patients. RNFL thickness gradually decreases while visual field defect increases with the development of POAG. PMID- 11780420 TI - Molecular cloning and characterization of NAG-7: a novel gene downregulated in human nasopharyngeal carcinoma. AB - OBJECTIVE: To identify novel tumor suppressor genes at chromosome 3p24-26 in human nasopharyngeal carcinoma (NPC). METHODS: Twenty epithelial-derived expressed sequence tags (EST) were selected from chromosome 3p24-26. RT-PCR and Northern blot were used to detect the expression of the ESTs in NPC cell line, HNE-1, and primary cultures of normal nasopharyngeal epithelial cells. One EST, which was substantially downregulated in the HNE-1 cell line, was detected in 19 NPC biopsy samples. cDNA library screening was used to get its full sequence and the sequence of this novel gene was analyzed. RESULTS: A novel gene located at chromosome 3p25.3 was obtained and named NAG-7. It was downregulated in 26.3% (5/19) of NPC biopsy samples. Its 1677 bp full length cDNA had a potential open reading frame predicting a 94 amino acid protein with a molecular weight of 11,023.87 Dalton. Analysis of the NAG-7 gene showed that it was a transmembrane protein containing a protein kinase C phosphorylation site and a myristyl site. It has no significant homology to any reported genes in the database of GenBank. CONCLUSION: NAG-7 is a novel gene downregulated in NPC, suggesting that it may be involved in the development of NPC. PMID- 11780421 TI - Increased expression of Hsp70 and co-localization with nuclear protein in cells infected with the Hantaan virus. AB - OBJECTIVE: To investigate the effect of Hantaan virus infection on the expression of stress genes. METHODS: Techniques of virus infection, Western blot, immunohistochemistry, dual-immunofluorecsence staining, laser scanning confocal microscopy, RNA dot blot and in situ hybridization were used. RESULTS: Expression of heat shock protein 70 (Hsp70) was observed in cells infected with HTV as well as the translocation of Hsp70 from cytoplasm to nucleoli following virus infection. The variable distribution of Hsp70 was related to the various time after infection. Double-label indirect immunofluorescence of nuclear protein (NP) and Hsp70 in infected cells demonstrated co-localization of these proteins in the cytoplasm. CONCLUSION: Overexpression of Hsp70 can be induced directly by Hantaan virus, which may be associated with virus protein assembly. The Hantaan virus proteins co-localize with, and possibly form a physical complex with cellular Hsp70 in infected cells. PMID- 11780422 TI - Diagnosis and treatment of bronchial rupture from blunt thoracic trauma. AB - OBJECTIVE: To evaluate the diagnosis and management of bronchial rutpture from blunt thoracic trauma. METHODS: A group of 31 patients with bronchial rupture was involved. Chest roentgenography, tomography and bronchoscopy were performed on all patients. The surgical technique and complications were described. RESULTS: Diagnosis was confirmed by tomography and bronchoscopy in all the patients. End to end anastomosis was used in 26 patients. Four patients were operated with total pneumonectomy. One patient was repaired with an intercostal muscle and rib flap with blood supply. Of the 31 patients, one died of adult respiratory distress syndrome after operation. Most patients had excellent surgical outcomes. 81% (25/31) of the bronchial rupture were delayed in diagnosis and treatment. The classic symptoms and signs of bronchial rupture included subcutaneous emphysema, dyspnea and an intermediate coma interval. The roentgenogram showed mediastinal emphysema, pneumothorax, "drop lung" sign and marked radiodensity of hilum widened mediastinum. CONCLUSION: Bronchoscopy is a useful and accurate method to diagnose and treat the bronchial rupture, with which surgeons can easily locate the rupture site during surgery. Surgical treatment could restore pulmonary function in most patients. PMID- 11780423 TI - Cordotomy for bilateral cord abductal paralysis. AB - OBJECTIVE: To investigate the clinical effects of cordotomy on bilateral cord abductal paralysis. METHODS: With unilateral cordotomy, we treated 4 patients with bilateral cord paralysis whose glottis size was about 2.0 mm to 2.5 mm. They were followed up for over one year. RESULTS: One week after surgery, the tracheotomy tubes of all 4 patients were plugged and no dyspnea occurred during rest and mild action. Their voices were more hoarse than before surgery. After 3 months, the tracheotomy tubes were successfully decannulated, and in the following one year, their respiration was normal and then speech was clear, although their voices were still a little hoarse. CONCLUSION: We suggest that cordotomy be one option in the treatment of bilateral cord abductal paralysis. PMID- 11780424 TI - Primary carcinoid tumor of the epididymis. PMID- 11780425 TI - Transurethral microwave needle ablation for bladder cancer. PMID- 11780426 TI - Interventional therapy for congenital heart disease (CHD). PMID- 11780427 TI - Interaction of hypertension and diabetes on impairment of endothelial function. AB - OBJECTIVE: To investigate whether the interaction of hypertension and diabetes aggravates endothelial dysfunction and leads to smooth muscle dysfunction. METHODS: Noninvasive methods were used to the investigated patients with type 2 diabetes mellitus (2-DM) (Group 1), patients with hypertension (Group 2) and patients with both 2-DM and hypertension (Group 3), as well as a normal control group (Group 4) by studying a brachial artery without evidence of atherosclerotic plaque formation. RESULTS: Results showed that endothelium-dependent vasodilation decreased significantly in Group 1 (5.74% +/- 3.32%, P < 0.05), Group 2 (4.14% +/ 2.93%, P < 0.01), and Group 3 (2.78% +/- 2.08%, P < 0.001) as compared to the control (9.45% +/- 3.88%). The nitroglycerin-induced vasodilation (smooth muscle function) in Group 3 was significantly decreased as compared to the control group (14.11% +/- 4.63% vs 23.53% +/- 6.77%, P < 0.001), but there were no differences in nitroglycerin-induced vasodilation between Group 1, Group 2 and Group 4. On univariate analysis, a reduced vasodilator response to nitroglycerin was associated with endothelium-dependent vasodilation (r = 0.54, P < 0.001). CONCLUSION: Our results indicate that the interaction of 2-DM and hypertension aggravates endothelial dysfunction and further impairs the smooth muscle function. PMID- 11780428 TI - Implantation of dual chamber pacemaker defibrillator and placement of endocardial leads via the axillary vein. AB - OBJECTIVES: To assess the preliminary clinical results of implantation of dual chamber pacemaker defibrillator and to evaluate the safety and effectiveness of placement of endocardial leads in the axillary vein. METHODS: Seven patients with ventricular tachycardia and/or ventricular fibrillation (VT/VF), associated with bradyanhythmia received implantation of a dual chamber pacemaker defibrillator, including 5 patients with coronary artery disease and 2 patients with dilated cardiomyopathy. The atrial and ventricular leads were introduced via the axillary vein under venographic guidance. RESULTS: Dual chamber pacemaker defibrillators were successfully implanted in the left chest subcutaneous pocket in 5 patients and the left pectoral muscular pocket in 2 patients. All the VT/VF occurring either inducibly during the procedure or spontaneuously during follow-up were detected promptly and treated successfully. Both the pacing and sensing functions were satisfactory. The endocardial leads required were successfully introduced via the axillary vein without major complications. CONCLUSIONS: Dual chamber pacemaker defibrillators can provide reliable therapy for VT/VF and the dual chamber pacing function. Placement of endocardial leads via the axillary vein under venographic guidance is safe and effective. PMID- 11780429 TI - Effect of aloe-emodin on expression of proliferating cell nuclear antigen of vascular smooth muscle cells in culture after arterial injury. AB - OBJECTIVE: To observe the effect of aloe-emodin on the expression of proliferating cell nuclear antigen (PCNA) in smooth muscle cells (SMCs) after arterial injury and study the molecular mechanism of inhibition of aloe-emodin on SMC proliferation. METHODS: Deendothelialization was performed at the abdominal aorta in Japanese white rabbits using a 3F Fogarty arterial embolectomy catheter. 48 hours later, the medium of abdominal aorta was isolated and primary SMCs culture was performed. Cells were synchronized to G0 by serum starvation, then aloe-emodin at a concentration of 20 micrograms/ml was added to the culture medium containing 10% [v/v] fetal calf serum. Vehicle was also added to the medium as a control. After 18 hours, the expression of PCNA at the level of mRNA and protein were examined using techniques of RT/PCR, Western blotting and inmmunocytochemistry respectively. RESULTS: Compared with the control group, the expression of PCNA mRNA and protein was prominently decreased after addition of aloe-emodin. CONCLUSION: The inhibition of aloe-emodin on SMCs proliferation may be caused by inhibiting the expression of the PCNA gene. PMID- 11780430 TI - Angiotensin II type 1 receptor modulation of L-type calcium currents in guinea pig ventricular cells. AB - OBJECTIVE: To study the cellular mechanism of the effect of Ang II on ICa,L in single guinea-pig ventricular cells by using losartan and 1-(5 lsoquinolinylsulfonyl)-2-Methyl-Piperazine (H-7) as the Ang II type 1 receptor (AT1) inhibitor and protein kinase C inhibitor, respectively. METHODS: Patch clamp techniques were used to study the cellular mechanism of the effect of Ang II on ICa,L in single guinea-pig ventricular cells. RESULTS: In the whole cell patch clamp recording model, Ang II stimulated ICa,L in a concentration dependent manner; the maximal effect was obtained at 100 nmol/L (n = 9). At 30 nmol/L, Ang II stimulated peak ICa,L from 11.3 +/- 0.6 pA/pF to 15.3 +/- 0.6 pA/pF (at + 10 mV, n = 9, P < 0.05). 100 nmol/L Losartan, a specific AT1 receptor inhibitor, had no effect on ICa,L (n = 9), but the effect of Ang II on ICa,L was inhibited by 100 nmol/L Losartan. Ang II on ICa,L was also inhibited by 20 mumol/L H-7, a specific protein kinase C inhibitor, whereas H-7 alone has no effect on ICa,L (n = 9). CONCLUSION: Ang II stimulates ICa,L in guinea-pig ventricular cells by binding to AT1 through a transduction pathway involving protein kinase C. PMID- 11780431 TI - The expression of AT1 receptor on hepatic stellate cells in rat fibrosis induced by CCl4. AB - OBJECTIVES: To assess the effect of an ACE inhibitor and an Ang II type 1 (AT1) receptor antagonist on preventing hepatic fibrosis induced by CCl4 in rats and to investigate whether there is the expression of AT1 receptors on hepatic stellate cells. METHODS: Studies were conducted in male Sprague-Dawley rats. Except for model group and control group, in three treated groups, either enalapril (5 mg/kg), or losartan (10 mg/kg), or enalapril + losartan were given to the fibrotic rats (daily gavage). Saline vehicle was given to the control group. After 6 weeks, liver fibrosis was assessed directly by hepatic morphometric analysis. The expression of AT1 receptors and alpha-smooth muscle actin (alpha SMA) in liver tissue and isolated hepatic stellate cells (HSC) were detected by immunohistochemical techniques. RESULTS: Compared with the fibrosis in rats of the model group, rats treated with either enalapril or losartan, or a combination of two drugs, showed a limited expansion of the interstitium (P < 0.05), but no significant difference was observed among the three treated groups (P > 0.05). The expression of AT1 receptors was found in abundance in the fibrotic interstitium of the fibrotic rats, whereas in the normal control rats they were limited to the vascular wall. AT1 receptors were also expressed on activated HSC in culture plates. CONCLUSIONS: Angiotensin-converting enzyme inhibitors and AT1 blockers might slow the progression of hepatic fibrosis. Activated HSCs expressed AT1 receptors. Activation of RAS might be related to hepatic fibrogenesis induced by CCl4. PMID- 11780432 TI - Detailed deletion mapping on chromosome region 9p21 in human periampullary neoplasms. AB - OBJECTIVE: To further define the extent of chromosome 9p21 deletion in periampullary neoplasms. METHODS: The loss of heterozygosity at 5 microsatellite polymorphic markers on chromosome 9p21 was detected by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis (PAGE) and silver staining in 35 specimens of periampullary neoplasms and their matching blood samples. RESULTS: Fifty percent (4/8) of pancreatic cancer cases showed the loss of heterozygosity at one or more microsatellite loci, with the more frequent sites of D9S974 (37.5%) and D9S942 (28.6%), and some showing consecutive allelic loss. Sixty-two point five percent (5/8) of ampullary carcinoma cases showed loss of heterozygosity at one or more of the loci, frequent site of loss being D9S942 (42.9%) and the next most frequent being IFNA (37.5%) and D9S171 (37.5%). Loss of one locus was observed in 14.2% (1/7) of insulinoma. CONCLUSION: The minimal common region of chromosome deletion in periampullary neoplasms is defined between the D9S974 and D9S942 loci within a 15 kb interval in 9p21, suggesting the involvement of a novel tumor suppressor gene in their carcinogenesis. PMID- 11780434 TI - Serum granulocyte colony-stimulating factor in patients with chronic renal failure. AB - OBJECTIVE: To gain a better understanding of the regulatory mechanism and kinetic behaviour of granulocyte colony-stimulating factor (G-CSF). METHODS: An enzyme linked immunosorbent assay (ELISA) method was used to detect serum G-CSF in 61 patients with chronic renal failure +/- long-term hemodialysis and 30 normal controls. RESULTS: Serum G-CSF levels in CRF patients were significantly higher than in normal controls. Eighty percent of patients had detectable G-CSF and serum G-CSF levels were 566.40 +/- 207.98 ng/L in non-hemodialyzed (non-HD) patients. The detectable percentage in hemodialyzed patients was 93.33%, serum G CSF levels in pre-HD and post-HD patients were 1255.36 +/- 611.25 ng/L and 1151.61 +/- 599.47 ng/L respectively. Serum G-CSF levels in HD patients were slightly higher than in non-HD patients, but no significant difference was found between the two groups. No difference was found between the G-CSF values obtained in pre-HD and post-HD patients. There was no relationship between G-CSF levels and WBC, BUN or Scr (P > 0.05). CONCLUSION: The high value of G-CSF in patients with CRF may be caused by a decrease in G-CSF clearance and/or an increase in G CSF release. PMID- 11780433 TI - Effects of acute or prolonged exposure to leptin on hepatic glucose oxidation. AB - OBJECTIVE: To observe the short-term and long-term effects of leptin on hepatic glucose oxidation and glucokinase gene expression. METHODS: Rat hepatic cell line BRL was incubated with leptin of different doses (range from 10 ng/ml-200 ng/ml) for 1 h or 24 h. Glucose oxidation was determined by liquid scintillation counting. Glucokinase gene expression (corrected by beta-actin) was determined by reverse transcription semi-quantitative polymerase chain reaction. RESULTS: Treatment with leptin 10 ng/ml for 1 h had no significant effects on glucose oxidation in hepatic cells. However, at the doses ranging from 50 ng/ml to 200 ng/ml, leptin significantly inhibited glucose oxidation. These effects disappeared when the hepatic cells were exposed to leptin for 24 h. Glucokinase mRNA expression was reduced significantly after both 1 h and 24 h exposure to leptin (100 ng/ml) as compared to that of the control group. CONCLUSION: A low dose of leptin has no significant effect on glucose oxidation in hepatic cells. A relatively high dose of leptin has an acute inhibitory effect on the glucose oxidation in hepatic cells. This effect may likely involve the inhibition of glucokinase gene expression. The inhibitory effect on glucose oxidation is transient and disappears with prolonged exposure time. PMID- 11780435 TI - In vitro study on the morphology of human blood dendritic cells and LPAK cells inducing apoptosis of the hepatoma cell line. AB - OBJECTIVE: To observe in vitro effects and morphological changes of human peripheral blood dendritic cells (DCs) on the ability of lymphokine and phytohaemagglutininum (PHA) activated killer (LPAK) cells to induce apoptosis of the human hepatoma cell line (BEL-7402, B). METHODS: Experimental groups were divided into LD group (DCs + L + B), L group (L + B), D group (DCs + B) and B group. The methods of neutral red uptake, ordinary light microscopy, electron microscopy, TDT mediated X-dUTP nick end labeling (TUNEL) were used. RESULTS: The difference between the D group and the B group was not distinct (P > 0.05). The difference between the LD group and the L group was distinct, with DCs + LPAK > LPAK (P < 0.01) in cytotoxicity. Apoptotic cells were TUNEL positive in light microscopy, and apoptotic nuclei were stained yellow brown and dark brown, with size and shape varying from cell to cell. Ultrastructural change in apoptotic tumor cells comprised of compaction and condensation of nuclear chromatin, and condensation of cytoplasm and apoptotic bodies. At the same time, LPAK cells manifested the characteristics of autophagic apoptosis, and there were some autophagic bodies in it. CONCLUSIONS: The combination of human blood DCs and LPAK cells could induce apoptosis of BEL-7402 cells effectively, with some LPAK cells manifesting the characteristics of autophagic apoptosis. PMID- 11780436 TI - Activity identification of anti-caspase-3 mRNA hammerhead ribozyme in both cell free condition and BRL-3A cells. AB - OBJECTIVE: To study the transcription effects and cleavage activities of rat caspase-3 specific hammerhead ribozyme (Rz107) in both cell-free conditions and BRL-3A cells. METHODS: Rat caspase-3 gene fragment was cloned into the pGEM-T EASY vector under the T7 promoter control. The 32P-labeled caspase-3 transcript was the target-RNA. Rz107 genes designed against caspase-3 mRNA were cloned into vector p1.5 between 5'-cis-Rz and 3'-cis-Rz. 32P-labeled ribozyme transcripts were incubated with target-RNAs at different conditions and autoradiographed after denaturing gel-electrophoresis. Rz107 was electroporated into BRL-3A cells and the Rz107 expression was analyzed by RT-PCR. RESULTS: In cell-free conditions, Rz107 was active at 37 degrees C. The optimal temperature was 50 degrees C. The Km and Kcat were 14.13 nmol/L and 2.31.min-1 respectively. Intracellular cleavage efficiency of Rz107 was 37%, as analyzed by RT-PCR. This indicated that the design of Rz107 was correct, and Rz107 had the activity of common enzymes. CONCLUSIONS: Rz107 in cell-free conditions possessed perfect specific catalytic cleavage activity, and it can also cleave the target RNA successfully in cells. The results illustrate the feasibility of ribozyme therapy as a potential alternative approach for treating liver disease caused by apoptosis. PMID- 11780437 TI - Efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria. AB - OBJECTIVE: To evaluate the clinical efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria. METHODS: Fifty-four patients with symptomatic falciparum malaria were allocated to receive oral dihydroartemisinin at a single dose of 120 mg on day 1, followed by mefioquine, 750 mg and 500 mg on days 2 and 3, respectively. Follow-up was performed on days 1, 2, 3, 4, 7, 14, 21, and 28. RESULTS: All patients had a rapid initial response to treatment. The parasite clearance time (PCT) after treatment was 30.7 +/- 3.6 hours. The fever subsidence time (FST) after treatment was 21.2 +/- 2.8 hours. Two patients had a recrudescence 21 and 25 days respectively after the disappearance of parasitemia, hence the recrudescence rate was 3.7% and the cure rate was 96.3%. No serious adverse effects were observed, only mild and transient nausea, vomiting and loss of appetite. CONCLUSION: A combination of dihydroartemisinin and mefloquine is effective in the treatment of acute uncomplicated falciparum malaria. PMID- 11780438 TI - Isolation and specific detection of two major schistosoma gut-associated circulating antigens. AB - OBJECTIVES: To investigate the nature of the common epitopes of Schistosoma japonicum (S. japonicum) circulating anodic (CAA) and circulating cathodic antigen (CCA) and to try to obtain sufficient purified material to set up a standard series for quantitative determinations. METHODS: Isolation of the two worm fractions from a trichloroacetic acid (TCA) soluble preparation of S. japonicum adult worm antigen (AWAj-TCA) via Mono-Q anion exchange chromatography was performed and analysis of specific reactivity of the eluted fractions was done by antigen-capture Enzyme Linked Immuno Sorbent Assay (ELISA) specific for CAA or CCA with reference to affinity purified preparations of S. mansoni CAA and CCA. RESULTS: When an ionic strength gradient was used, CCA was eluted in two major peaks, an unbound fraction CCA-1, and a major bound fraction, CCA-2. Two additional minor peaks, CCA-3 and CCA-4, were eluted at higher ionic strengths. CAA was only detected in the bound fraction, partly overlapping with CCA-3. In the CCA-1 and CCA-2 fractions, reactivity was only found in the antigen-capture ELISA using anti-CCA McAbs both for capture and detection. The CAA fraction was predominantly found to be positive in the antigen-capture ELISA using anti-CAA McAbs both for capture and detection. However, in ELISA using combined anti-CAA and anti-CAA McAbs for capture and detection, this fraction showed some reactivity. CONCLUSION: The two CCA fractions contain molecules which bear at least two CCA-epitopes; the CAA fraction contains molecules which contain at least two CAA-epitopes, and one CCA-epitope. PMID- 11780439 TI - Characterization of urocortin in human pregnancy. AB - OBJECTIVE: To examine whether urocortin is produced locally to regulate utero placental vascular tone during pregnancy. METHODS: We examined the distribution of urocortin in human placenta, fetal membranes and uterine tissue at term in the presence and absence of labor using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro using an immunoblot technique. Then, we tested whether urocortin is present in maternal plasma throughout gestation using a radioimmunoassay. A Sephadex G-50 column was used to examine whether immunoreactive urocortin (IR-urocortin) in maternal plasma is the same as synthetic urocortin. RESULTS: IR-urocortin was observed in vascular smooth muscle of myometrium decidual stromal cells, syncytiotrophoblast and amnion epithelium. No differences in staining intensity for urocortin were detected between tissues obtained in the absence or presence of labor. Staining intensity for IR-urocortin was greatest in the decidua, suggesting this may be the main site of urocortin production. Positive staining for urocortin was observed in 40% of chorio-decidual cells with 34% of these cells secreting urocortin under basal conditions. Urocortin was detectable in maternal plasma from 16 weeks gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention co efficient of 0.44. CONCLUSION: This study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate utero-placental blood flow. PMID- 11780440 TI - Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines transfected with costimulatory B7 gene. AB - OBJECTIVE: To investigate the effect of U14 vaccine transfected with the B7 gene in inducing antitumor immune response to murine cervical carcinoma in Chinese 615 strain mice. METHODS: A recombinant retroviral plasmid vector expressing mouse B7 1 gene (pLNSX-mB7) was transfected into 615-strain mouse cervical carcinoma cell line No. 14 (U14) by electroporation to set up a highly-expressed mB7-1 U14 cell clonal strain (B7+ U14). In vivo experiments: (1) B7+ U14 vaccine was primed to protect the 615-strain mice against U14 re-challenge. (2) B7+ U14 vaccine was injected into tumor-bearing mice with different tumor sizes. Lifetimes and tumor sizes were recorded. In vitro cytotoxicity assay: Mice were immunized with B7+ U14 or U14 vaccine and 2 weeks later, spleen cells of those mice were cultured for 2 days. The cytotoxicity of these cells against U14 was detected by 5 diphenyl tetrazolium bromide assay. RESULTS: We obtained several B7-1 high expression clonal U14 lines. In vivo experiment, we did not find tumor growing in 3 of the 6 mice primed by B7+ U14 vaccine during their entire life after re challenge with U14. The other 3 mice developed tumors and their average survival time was longer than that of the control group (P < 0.01). All 6 mice grew tumors in the control group. When the transplanted tumors became palpable, the mice were randomly divided into 3 groups to be injected with B7+ U14 vaccine. It was effective for tumor-bearing mice only when the tumor diameters were < 3 mm. When the diameters were > or = 3 mm, it was not efficacious to inject B7+ U14 vaccine (P < 0.05). In vitro cytotoxicity assay, cytotoxic T lymphocytes induced by B7+ U14 vaccine had a higher cytotoxicity against U14 than that induced by U14 vaccine (F = 310.8, P < 0.001). CONCLUSIONS: Vaccines of cervical cancer cells transfected with the costimulatory molecule B7 gene can induce antitumor immune protection in host mice against U14 re-challenge. This treatment may cure part of the tumor-bearing mice but be restricted by tumor size. The results suggest that transfecting the B7 gene into cervical cancer as a cell vaccine may be an efficient supplementary method to treat cervical cancer after operation. PMID- 11780442 TI - Incidence of deep venous thrombosis after gynaecological laparoscopy. AB - OBJECTIVE: To evaluate the incidence of deep venous thrombosis (DVT) after gynaecological laparoscopy. METHODS: The incidence of DVT was studied in 72 consecutive patients who underwent gynaecological laparoscopy in the Liverpool Health Service between May and September 1997. B-mode ultrasound supplemented by Doppler was used to examine venous patency and intraluminal echoes to diagnose DVT. Sixty-one patients who had pneumoperitoneum less than 60 minutes were classified a minor procedure and 11 who had pneumoperitoneum more than 60 minutes were classified as major procedure. Two Doppler ultrasound scans were planned for every patient. The first one was done within 24 hours and the second was performed on day 7 post-surgery. All 72 patients had the first scan and 40 out of 61 in the minor procedure group and 9 out of 11 in the major procedure had the second scan. Twenty-three patients who did not come for the second scan were followed up by phone. RESULTS: No DVT was found in our study. CONCLUSION: This study confirms an impression that gynaecological laparoscopic procedure has a very low incidence of DVT. If it occurs, the diagnosis and treatment must be made as soon as possible so that the fatal complications such as pulmonary embolus can be avoided. PMID- 11780441 TI - Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol. AB - OBJECTIVE: To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol. METHODS: Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. RESULTS: The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91 +/- 20.74 IU/mg.protein and 64.25 +/- 35.81 IU/mg.protein respectively, lower than those in the normal decidua group (99.76 +/- 58.61 IU/mg.protein, P < 0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43 +/- 0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90 +/- 0.16) was not significantly different from that in the normal decidua group (0.94 +/- 0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P > 0.05). CONCLUSIONS: Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion. PMID- 11780443 TI - Placental leptin correlates with intrauterine fetal growth and development. AB - OBJECTIVE: To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. METHODS: Forty women and their babies (40) were enrolled in this study. Placental tissues were assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR), and assayed for the obese gene protein leptin by Western-blot and immunohistochemistry. Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin, cord leptin and neonatal anthropometric measures. RESULTS: The obese gene was expressed in placental tissue at comparable or greater levels than that in adipose tissue. The placentas of the small for gestational age (SGA) neonates expressed leptin mRNA and protein at significantly lower levels than those of the appropriate for gestational age (AGA) neonates (P = 0.0034 and 0.0076), while the placentas of the large for gestational age (LGA) neonates expressed leptin mRNA and protein at significantly higher levels than those of the AGA neonates (P = 0.043 and 0.021). Linear regression analysis showed placental ob gene transcription and leptin translation correlated significantly with cord leptin (r = 0.39 and 0.43), and neonatal Ponderal Index (r = 0.66 and 0.69). CONCLUSION: The placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development. PMID- 11780444 TI - Apoptosis within mouse eye induced by Toxoplasma gondii. AB - OBJECTIVE: To investigate apoptosis induced by Toxoplasma gondii (T. gondii) in eyes of C57BL/6 (B6) mice. METHODS: Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) technique and pathological changes within eyes were analyzed at different time points after intraocular inoculation of either 50 or 500 of tachyzoites. RESULTS: In eyes that received 50 tachyzoites, a few apoptotic inflammatory cells in the anterior chamber and keratocytes in the cornea were seen at days 1 and 2, but no apoptosis was detected 4 days after inoculation. Significantly greater apoptosis of inflammatory cells was observed in the anterior chamber and in the vitreous of eyes injected with 500 parasites. Apoptosis of inflammatory cells in the anterior chamber and of keratocytes in the cornea was seen at day 1. The apoptotic stromal keratocytes strikingly increased at day 4. There were a number of apoptotic inflammatory cells in the vitreous at day 2, and a few apoptotic retinal cells along the internal limiting membrane and the nerve fiber layer of the retina 4 days after inoculation. CONCLUSION: These results suggest that apoptosis of inflammatory cells infiltrated eye infected with this parasite may be a mechanism of eliminating the organism. PMID- 11780445 TI - Magnetic resonance imaging in distinguishing malignant from benign pleural disease. AB - OBJECTIVE: To explore the role of magnetic resonance imaging (MRI) in distinguishing malignant from benign pleural disease. METHODS: All 64 patients were examined with both computed tomography (CT) and MRI. The morphologic features of pleural lesions and MR signal intensity on T1-weighted, T2-weighted and contrast-enhanced T1-weighted images were evaluated. RESULTS: Mediastinal pleural involvement, circumferential pleural thickening, nodularity, irregularity of pleural contour, and infiltration of the chest wall and/or diaphragm were most suggestive of a malignant cause on CT and MR images. Contrary to what has been reported in the literature, pleural thickness greater than 1 cm either on CT or on MRI did not reveal a significant difference between malignant and benign pleural disease (P > 0.05, chi-square test). Using morphologic features in combination with signal intensity features, MRI had a sensitivity of 98% and a specificity of 92% in the detection of pleural malignancy. CONCLUSIONS: Compared with those on CT, the morphologic features on MRI allowed a mostly equal and in some cases superior detection and evaluation of the spread of pleural disease. In combination with signal intensity and morphologic features, MRI is very useful in distinguishing malignant from benign pleural disease. PMID- 11780446 TI - Gene transfer and expression in rat anastomotic artery in vivo using adenoviral vector. AB - OBJECTIVE: To observe the efficiency and time course of gene expression and the safety of adenoviral vector mediated gene transfer in vivo. METHODS: After soaking soluble stents in a high concentration of glucose solution containing Adv5-CMV (cytomegalovirus) (control group) or Adv5-CMV/LacZ (treatment group) for 30 minutes, the stents were inserted into the lumina of cut rat carotid arteries and end-to-end anastomoses of the cut carotid were performed with standard microvascular surgical techniques. On days 2, 7, 14, 28, 60 and 90 after gene transfer, anastomotic arteries of the two groups were observed. On days 7 and 14, the ascending aortas, hearts, brains, livers, lungs, spleens and kidneys of the treatment group were observed. All samples were analyzed for the presence of beta galactosidase activity and histochemical staining. RESULTS: beta-galactosidase activity was not detected in the carotid arteries of the control group and organs not directly exposed to adenoviral vector of the treatment group. The amount of beta-galactosidase activity (x 10(-3) U/g tissue) in the treatment group on the 2nd, 7th, 14th, 28th, 60th and 90th day after gene transfer was 3.87, 11.38, 9.8, 6.43, 3.18 and 2.43, respectively. Microscopic examination of sections from vessels of the control group and from the aortas, hearts, brains, livers, lungs, spleens or kidneys of the treatment group revealed no X-gal staining. Microscopic examination of carotid arteries of the treatment group revealed blue-staining in all anastomotic arteries and in all layers of the arterial wall observed on days 7 and 14 after gene transfer. CONCLUSION: Adenoviral vector can effectively infect blood vessels in vivo. After adenoviral vector mediated direct gene transfer into anastomotic rat carotid arteries, recombinant gene expression began on day 2, peaked between days 7 and 14, prominently declined after day 28, and persisted at low levels more than three months. A recombinant gene could be delivered to a specific site by direct gene transfer in vivo by adenoviral vector infection. PMID- 11780447 TI - Nested polymerase chain reaction in detection of Plasmodium vivax sporozoites in mosquitoes. AB - OBJECTIVE: To detect malaria DNA in mosquitoes. METHODS: A nested polymerase chain reaction (nested PCR) procedure which amplifies a 121 bp DNA of a SSUrRNA gene specific to Plasmodium vivax was used. RESULTS: In laboratory-infected mosquitoes, nested PCR could detect as few as 3 sporozoites or 1 infected mosquito mixed in a group of 99 normal ones. Furthermore, no specific 121 bp band was seen with DNA templates from other malaria parasites or negative mosquitoes. CONCLUSION: Sensitivity and specificity obtained indicated an advantage of the nested PCR over DNA probes or direct PCR for the detection of Plasmodium vivax sporozoites in mosquitoes with low-grade parasitic infections. PMID- 11780448 TI - Efficacy of continuous tracheal gas insufflation in spontaneously breathing canine with acute lung injury. AB - OBJECTIVE: To investigate the effects of continuous tracheal gas insufflation (CTGI) combined with biphasic intermittent positive airway pressure (BIPAP) ventilation on dogs with spontaneous breathing. METHODS: Eight canine models with oleic acid induced lung injury and spontaneous breathing were ventilated in a random order by Evita 2 (Drager Inc., Germany) in modes of BIPAP (BIPAP group) and BIPAP with CTGI flow rate of 3, 6 and 9 L/min (T3, T6 and T9 groups), respectively. The setting parameters of BIPAP were fiction of inspired oxygen 60%, inspiratory to expiratory ratio 1:1, respiratory rate 20 and positive end expiratory pressure 5 cm H2O. Arterial and mixed venous blood gas, lung mechanics, systemic and pulmonary hemodynamics status were monitored at the same level of PaCO2 obtained by adjusting peak inspiratory pressure of BIPAP. RESULTS: Peak inspiratory pressure in the T6 group (14 +/- 4 cm H2O) and in the T9 group (11 +/- 3 cm H2O) were significantly lower than that of BIPAP (20 +/- 5 cm H2O, P < 0.01), but there was no significant difference among the T3, T6 and T9 groups or between the T3 and BIPAP groups. PaO2, mean artery blood pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, cardiac output, oxygen delivery and oxygen consumption all remained unchanged in four different conditions. CONCLUSIONS: Using BIPAP combined with CTGI does not cause asynchrony between ventilator and spontaneous breathing, but significantly decreases airway pressure with no influence on hemodynamics and oxygenation. Therefore, BIPAP with CTGI may be a useful support technique, especially in cases where the airway pressure should be limited. PMID- 11780449 TI - Guidelines to rational use of antibiotics in acute upper respiratory tract infections in Chinese children. PMID- 11780450 TI - An epidemiological survey on neonatal jaundice in China. AB - OBJECTIVE: To provide epidemiological data for revising the diagnostic criteria of neonatal hyperbilirubinemia in China. METHODS: A survey was performed among full-term infants in multiple centers throughout the country. From less than 24 hours after birth, the infants' bilirubin levels were measured every day until the peak level fell to less than 68.4 mumol/L. Auditory brainstem responses were assessed in 56 infants randomly chosen from those with serum bilirubin levels of higher than 220.5 mumol/L. RESULTS: Jaundice in most infants was detected at 2-3 days after birth. The bilirubin level usually reached a peak level of 204 +/- 54.69 mumol/L at 5 days after birth and then fell. Among the 875 infants, the serum bilirubin levels in 34.4% of neonates were higher than 220.5 mumol/L. The mean serum bilirubin level of the infants during the first week after birth varied with geography (P < 0.001) and season (P < 0.001). The serum bilirubin level was significantly associated with gestation age (P < 0.01), delivery method (P < 0.01), weight loss (P < 0.001), and PCV elevation (P < 0.001) during the first three days after birth. CONCLUSIONS: The start time of neonatal jaundice was similar to that reported elsewhere, but the mean peak level in our study was higher than the reported. It is suggested that the diagnostic criteria for neonatal hyperbilirubinemia in China should be strict. PMID- 11780451 TI - The preparation of rat heme oxygenase-1 mutant to reduce the level of bilirubin. AB - OBJECTIVE: To prepare rat heme oxygenase-1 (HO-1) mutants and to determine the activity and inhibition of this mutated enzyme. METHODS: pcDNA3HO1 containing truncated native rat HO-1 cDNA and pcDNA3HO1 delta 25 carrying mutated rat HO-1 cDNA (His25Ala) were constructed, respectively. COS-1 cells transfected with pcDNA3HO1 and pcDNA3HO1 delta 25 were collected and their activities were analyzed. RESULTS: Native rat HO-1 was highly expressed in transfected cells and its activity was 13,688-15,600 U/mg protein per hour. However, the enzyme activity of mutated HO-1 declined and the value was 1948-2160 U/mg protein per hour. When an equal amount of mutant was added to the enzyme reaction system, the level of bilirubin decreased by 42%. CONCLUSION: The His25Ala mutant reduced the formation of bilirubin, suggesting that the mutant could completely bind the heme with native enzyme. PMID- 11780452 TI - Hepatitis B virus S gene mutants in infants infected despite immunoprophylaxis. AB - OBJECTIVE: To assess the correlation between hepatitis B virus (HBV) surface gene mutant infection and hepatitis B (HB) vaccination failure. METHODS: Using sera from 106 infants who were born to HBV carrier mothers and failed in HB immunoprophylaxis, HBV S gene was amplified by PCR, transferred to nylon membranes for Southern blots, and then hybridized with oligonucleotide probes. Eleven of non-hybridizing samples were used for DNA sequencing. RESULTS: 93.4% (99/106) of the samples were HBV DNA positive, and 30.3% (30/99) failed to hybridize with at least one of the four probes. DNA sequencing confirmed that 10 of the 11 samples had an S gene mutation with amino acid (aa) change. The identified mutants included nucleotide (nt) 546T-->A (aa131N-->T), nt531T-->C (aa1261-->T), nt491A-->C (aa113T-->P), nt491T-->A (aa113S-->T), nt533C-->A (aa127P-->T), nt581T-->A (aa143S-->T), nt636A-->T (aa161Y-->F), and nt679A-->C (aa175L-->F). The sequence in one mother-infant pair was completely the same, with mutations at aa131 and aa161. CONCLUSIONS: The prevalence of HBV surface mutants is about 30% in the children failing in HB vaccination. HBV mutants can infect infants by maternal-infant transmission. PMID- 11780453 TI - Immunotoxin depletion of T cells and its effect on hematopoietic progenitor cells in human cord blood. AB - OBJECTIVE: To study the selective toxicity of immunotoxin (IT) on T cells in cord blood and simultaneously determine its effect on hematopoietic progenitor cells. METHODS: The percentage of CD5 and CD8 T cell subsets in cord blood (CB) and bone marrow (BM) as well as peripheral blood (PB) was measured by immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). One-way mixed lymphocyte cultures (MLC) were performed to compare the proliferative response of CB with that of PB. The proliferative capability of cord blood T cells and T lymphocyte transformation capacity were evaluated in the presence of anti-CD8 or anti-CD5 immunotoxin by one-way MLC and colorimetric MTT (tetrazolium) assay, respectively. The effect of IT on the growth of hematopoietic progenitor cell of colony forming unit-granulocyte and macrophage (CFU-GM), burst forming unit erythroid(BFU-E), multipotential hemotapoietic progenitors (CFU-Mix) from CB were estimated by colony-forming assays. RESULTS: A certain proportion of CD5 and CD8 T cells existed in CB. The alloproliferative capacity of CB was similar to that of PB. CD5: Ricin at a dosage of 1 x 10(-10)-1 x 10(-8) mmol/L and CD8: Ricin concentration in the range of 1 x 10(-9)-1 x 10(-8) mmol/L effectively decreased both the proliferative capability of T cells in MLC during CB and T cell transformation. Over the dosage of 1 x 10(-10)-1 x 10(-9) mmol/L, both kinds of IT didn't obviously affect the growth of hematopoietic progenitor cells. CONCLUSION: CD5: Ricin and CD8: Ricin may effectively deplete T cells and may not significantly inhibit the function of hemaptopoietic cells at a specific dosage. PMID- 11780454 TI - MR and cine-MR imaging in the diagnosis of infantile congenital heart disease. AB - OBJECTIVE: To assess the effectiveness of magnetic resonance imaging (MRI) and cine magnetic resonance imaging (cine-MRI) in the diagnosis of infantile congenital heart disease. METHODS: A total of 34 cases were studied with MRI and cine-MRI. The data were analyzed and compared with those of two-dimensional echocardiography (2DE), cardioangiography (CAG) and surgery. RESULTS: The size of the defect or its caliber obtained from MRI in 6 patients with left to right shunt congenital heart disease was compatible with that observed in surgery (P = 0.924). Comparison of cine-MRI and CAG in 28 patients with complicated congenital heart disease showed that the diagnosis of 27 cases by cine-MRI was the same as that by CAG. CONCLUSION: Both MRI and cine-MRI play an important role in diagnosing infantile congenital heart disease. PMID- 11780455 TI - Molecular epidemiology of respiratory syncytial virus. AB - OBJECTIVE: To determine the epidemiologic pattern of subgroups A and B and genotypes of respiratory syncytial virus (RSV) during two noncontinuous epidemics during 1990-1991 and 1997-1998 in Beijing. METHODS: Nasopharyngeal secretion (NPS) samples of RSV positive or RSV isolates tested by indirect immunofluorescence (IIF) assay were classified into subgroups A and B. Isolates of RSV were divided into at least six different lineages, designated NP1-NP6, by restriction mapping of the N gene. Np1, 3 and 6 were given by subgroup B isolates, while NP2, 4 and 5 were given by subgroup A isolates. Strains of subgroup A were further subdivided into six lineages SHL1-SHL6 on the basis of the SH gene sequence. SH lineages were closely related to each other and to NP1 NP6. Strains of SHL1, 3 and 4 were closely related and belonged to NP2, SHL2 and 6 to NP4, and SHL5 to NP5. RESULTS: Of 145 RSV NPS samples from the 1997-1998 epidemic, 83 (57.2%) were of subgroup B RSV positive, 62 (42.8%) of subgroup A RSV positive. The rate of occurrence of subgroup A to B strains was about 1:1.3. Two of 10 isolates during the epidemic were subgroup A strains, whereas 8 were subgroup B strains. The rate of occurrence of subgroup A to B strains was 1:4. Eight subgroup A strains of 10 isolates from the 1990-1991 epidermic were dominant; the proportion of subgroup A to B strains was 4:1. With 10 RSV isolates in 1997-1998, all 2 subgroup A strains gave N gene fragment restriction pattern NP4, and fell into SH lineage SHL2, whereas 8 subgroup B strains all belonged to NP3. All 8 subgroup A isolates from the 1990-1991 epidemic gave pattern NP4, and fell into SHL2, while 2 subgroup B strains all belonged to NP3. The classification of subgroups A and B deduced from NP patterns corresponded to the definition of these subgroups by monoclonal antibodies. CONCLUSIONS: These observations confirm that subgroups A and B or multiple lineages of RSV co circulated in Beijing, but different genome types predominated each year. Moreover, very similar viruses were isolated up to more than 5 years ago, indicating that despite apparent diversity of the subgroup A strains, the separate lineages might be relatively stable. PMID- 11780456 TI - Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy. AB - OBJECTIVE: To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. RESULTS: All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). CONCLUSION: Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle. PMID- 11780457 TI - The clinical and pathological characteristics of Chinese patients with pauci immune crescent glomerulonephritis. AB - OBJECTIVE: To investigate the clinical and pathological characteristics of pauci immune crescent glomerulonephritis (PICGN) in Chinese patients. METHODS: During 13 years (1985-1998), 6400 patients underwent non-transplanting renal biopsy. Twenty-four patients were diagnosed as PICGN. All clinical and laboratory data of these patients were collected from the patients' records and used for detailed analysis. The diagnosis is based on clinicopathologic findings. RESULTS: Of the 24 patients, 16 were females and 8 were males, with median age of 33 years (ranged 10-76 years). Microscopic polyarteritis (MPA) (33.3%) and systemic vasculitis (8.3%) were the secondary diseases. The incidence of PICGN was 0.38% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. At onset, gross hematuria was noted in 58.3% of patients, hypertension in 45.8%, nephrotic syndrome in 41.7%, and oliguria in 25.0%. However, systemic symptoms were rare except for anemia. Pathologically, necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in the interstitium (53.3%) were observed. In addition, glomerulosclerosis was noted in 45.8%, severe tubular atrophy in 83.3% and interstitial fibrosis in 75.0%. Anti-neutrophil cytoplasmic antibodies (ANCAs) were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were available for long-term follow up (median 29.8 months, range 8-92 months). Twelve of them had life-sustaining renal function, four had normal serum creatinine (< 124 mumol/L) and only 4 patients were dialysis-dependent. CONCLUSION: PICGN is not rare in China. Early diagnosis and administration of immunosuppressive therapy, particularly in patients with rapidly progressive glomerulonephritis (RPGN), are important for good prognosis. PMID- 11780458 TI - Factor V Leiden mutation in one family of Chinese origin. AB - OBJECTIVE: To investigate the factor V Leiden mutation associated with activated protein C resistance (APCR) in Chinese. METHODS: Thirty "normal" individuals and twenty patients with thrombotic disease from Chinese Han Nationality were studied with APTT +/- APC, PCR followed by MnLI restriction enzyme analysis, PCR based direct sequence-specific primers (PCR-SSP) and DNA sequence analysis. RESULTS: In one healthy control, the activated protein C (APC) sensitivity ratio (SR) was found to be significantly lower (0.8) than that in other normal control (> 2.0). This individual was identified to be heterozygous for FV Leiden mutation (Arg506 Gln). His grand-uncle, father, brother and son were also identified to be heterozygous for FV Leiden. The APC resistance was found in 3 other cases of thrombotic diseases, but with no FV Leiden mutation. CONCLUSION: This is the first four generations family case of FV Leiden mutation associated with APCR reported within Chinese ethnic population. It is note-worthy that more FV Leiden or whether other gene defects may be associated with APC resistance and acquired APCR causing thrombosis in Chinese population. PMID- 11780459 TI - Simian virus 40 large tumor antigen forms specific complexes with p53 and pRb in human brain tumors. AB - OBJECTIVE: To study the role of simian virus 40 (SV40) early region gene coding product large tumor antigen (Tag) expression and the interaction between Tag and tumor suppressors p53 and pRb in human brain tumorigenesis. METHODS: Tag was investigated by immunoprecipitation followed by silver staining and Western blot in 65 cases of human brain tumors and 8 cases of normal brain tissues. Tag-p53 and Tag-pRb complexes were screened in 18 and 15 Tag positive tumor tissues, respectively. RESULTS: Tag was found in all 8 ependymomas and 2 choroid plexus papillomas, 90% of pituitary adenomas (9/10), 73% of astrocytomas (11/15), 70% of meningiomas (7/10), 50% of glioblastomas multiforme (4/8), 33% of medulloblastomas (2/6). 5 oligodendrogliomas, 1 pineocytoma, and 8 normal brain tissues were negative for Tag. Tag-p53 complex was detected in all 18 Tag positive tumors. Tag-pRb complex was found in all 15 Tag positive tumors. CONCLUSION: SV40 Tag is expressed in human brain tumors and can form specific complexes with tumor suppressors p53 and pRb. The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb complexes may be an important mechanism in the etiopathogenesis of human brain tumors. PMID- 11780460 TI - Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury. AB - OBJECTIVE: To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). METHODS: Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. RESULTS: In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24 +/- 12.18 ng/L to 68.88 +/- 14.37 ng/L (P < 0.01); in control group, ET was reduced from 90.78 +/- 15.71 ng/L to 83.12 +/- 12.22 ng/L, with a statistically significant difference (P < 0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2 +/- 4.8 cm/s to 51.6 +/- 4.2 cm/s (P < 0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P < 0.01). CONCLUSION: HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure. PMID- 11780461 TI - Regeneration of nNOS-containing nerve fibers in rat corpus cavernosum. AB - OBJECTIVE: To investigate the effect of cavernous nerve injury on the nNOS containing nerve fibers in corpus cavernosum. METHODS: Thirty-three male Sprague Dawley (SD) rats were randomly divided into 3 groups: sham-operated controls (n = 5) underwent pelvic exploration without transection of the cavernous nerve; unilateral injury group (n = 14) had their cavernous nerve cut on one side; and bilateral injury group (n = 14) underwent neurotomy on both sides. Corpora cavernosa were harvested at the 3rd week and 6th month after surgery. nNOS positive nerve fibers were examined with streptavidin-peroxidase immunohistochemistry techniques (SP method). RESULTS: After bilateral ablation, the nNOS-positive nerve fibers were significantly decreased at the 3rd week (17 +/- 4) and remained so at the 6th month (16 +/- 4). For the unilateral injury group, the nNOS-positive nerve fibers were similarly decreased on the side of the neurotomy at the 3rd week (18 +/- 6), but by the 6th month, the number increased significantly (61 +/- 9) and approximated the level on the contralateral side (81 +/- 13). CONCLUSION: Following unilateral cavernous nerve ablation in rats, nNOS containing nerve fibers regenerate 6 months after surgery. This regeneration process does not occur in animals with bilateral cavernous nerve injury, suggesting that during radical pelvic surgery, the cavernous nerve has to be preserved at least on one side in order to maintain the capacity for penile erection. PMID- 11780462 TI - Infections caused by Flavimonas oryzihabitans. AB - OBJECTIVE: To assess retrospectively the clinical characteristics and cell immune function of infections caused by Flavimonas oryzihabitans (F. oryzihabitans). METHODS: We indentified 11 cases of F. oryzihabitans positive cultures from all microbial cultures collected in our hospital from November 1994 to December 1998. Relevant clinical information was collected, including demographic data, underlying disease, and clinical manifestations of the F. oryzihabitans infections. Minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the 11 F. oryzihabitans isolates were determined. Cell immune function tests were determined by flow cytometry including T lymphocyte subsets (CD3, CD4, CD8 and ratio CD4/CD8) and NK cells (CD16 + 56) from peripheral blood. RESULTS: Six of these patients with infections caused by F. oryzihabitans were male, 5 were female and the mean age was 47.64 years (range, 5 to 69 years). All but 1 patients had severe underlying diseases. 9 (81.8%) of these patients developed infection while hospitalization and 2 (18.2%) before hospitalization (Cases 2 and 5). 8 (72.7%) of these patients manifested primary F. oryzihabitans bacteremia and one each (9.1%) had pleurisy, soft tissue infection and peritonitis. All these isolates were susceptible to amikacin, gentamicin and ciprofloxacin, but resistance to cefazolin, nitrofurantoin, penicillin and piperacillin. CD3, CD4, CD4/CD8 and CD16 + 56 value (mean +/- s) of these patients were significantly lower than normal values (P < 0.01). The mean time of body temperature fell < or = 37 degrees C after antibiotic treatment in these patients was 3.5 days (range, 1 to 6 days). All clinical symptom caused F. oryzihabitans after antibiotic treatment disappeared and all patients recovered. CONCLUSIONS: Infections caused by F. oryzihabitans was very few clinically, and relative to underlying diseases and the presence of foreign material. Immune function abnormality was among mostly factor for the F. oryzihabitans infections. PMID- 11780463 TI - A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man. AB - OBJECTIVE: To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. METHODS: The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. RESULTS: Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. CONCLUSION: A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation. PMID- 11780464 TI - Apoptosis inducing effects of arsenic trioxide on human bladder cancer cell line BIU-87. AB - OBJECTIVE: To explore the apoptosis inducing effects of arsenic trioxide (As2O3) on human bladder cancer cells and elucidate possible mechanisms. METHODS: After treatment with As2O3, the growth inhibition rates of human bladder cancer cell line BIU-87 were studied by MTT and cell counts methods. DNA synthesis rates were detected by 3H-TdR assay. The morphological changes of cancer cells were observed by light and electronic microscopy and cell apoptosis rates were detected by TdT mediated dUTP nick end labeling (TUNEL). bcl-2 gene expression of BIU-87 cells was observed by strept avidin-biotin complex (SABC) immunohistochemical method. RESULTS: As2O3 could effectively inhibit the growth of BIU-87 (P < 0.05), which were time and concentration dependent. The inhibition rate of 4.0 mumol/L As2O3 for DNA synthesis of cancer cells was 55.64% (P < 0.01). Partial cancer cells presented the characteristic morphological changes of apoptosis which depended on the time of exposure to drug (P < 0.05). bcl-2 expression of BIU-87 cells was decreased significantly (P < 0.05). CONCLUSION: As2O3 can significantly induce apoptosis in bladder cancer cells by down-regulating the expression of the bcl-2 gene and inhibiting DNA synthesis. This provides a potentially effective method for prevention and cure of human bladder cancer. PMID- 11780465 TI - Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes. AB - OBJECTIVE: To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. METHODS: Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. RESULTS: DRB1 * 0301, DQA1 * 0301, DQB1 * 0201 alleles and DRB1 * 0301-DQA1 * 0501-DQB1 * 0201 haplotype were significantly increased in patients, while DQA1 * 0103 and DQB1 * 0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. CONCLUSIONS: DRB1 * 0301, DQA1 * 0301 and DQB1 * 0201 confer susceptibility while DQA1 * 0103 and DQB1 * 0601 confer protection to type 1 diabetes. DRB1 * 0301-DQA1 * 0501-DQB1 * 0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up. PMID- 11780466 TI - Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients. AB - OBJECTIVE: To clarify the role of vitamin D receptor (VDR) expression in parathyroid proliferation and resistance of parathyroid glands to 1,25(OH)2D3 with secondary hyperparathyroidism (SHPT). METHODS: This study used archive parathyroid with 7 uremic patients. The expression of proliferation cell nuclear antigen (PCNA) and VDR was evaluated in nineteen-surgically excised parathyroid tissues, including 11 diffuse hyperplasia (DH-type) and 8 nodular hyperplasia (NH type) of parathyroid glands, by immunohistochemistry (avidin-biotin complex method). RESULTS: The weight of parathyroid in SHPT was remarkably increased by 16.1 times. The numbers of parathyroid cells were increased by 1.86 times. The rate of PCNA was remarkably increased in parathyroid hyperplasia with SHPT compared with that in control group [(6.35 +/- 3.36)@1000 vs (1.73 +/- 1.31)@1000, P < 0.001]. The number of PCNA in DH-type was lower than that in NH type (P < 0.001). The density of VDR in the parathyroid with SHPT was significantly decreased [(40.28 +/- 13.13)% vs (83.79 +/- 3.77)%, P < 0.001], VDR immunoreactivity expression in NH-type was lower than that in DH-type [(27.14 +/- 4.12)% vs (49.84 +/- 7.33)%, P < 0.001]. A significantly negative correlation was found between VDR density and the weight of the parathyroid (r = -0.46, P < 0.05), the same as VDR and PCNA (r = -0.75, P < 0.001). CONCLUSION: VDR density was significantly decreased in parathyroid tissue of uremic patients showing nodular hyperplasia compared with that in diffuse hyperplasia and there was significantly negative correlation between VDR density and the weight of the parathyroid, and this may contribute to the progression of SHPT. Furthermore, VDR deficiency may cause the resistance of parathyroid cells to 1,25(OH)2D3, in part. PMID- 11780467 TI - Effects of acidum vitamin A on tyrosinase activity. AB - OBJECTIVE: To investigate the effect of acidum vitamin A on tyrosinase activity and provide experimental evidence for therapy of pigment disorder of skin. METHODS: Tyrosinase activity was estimated by measuring the rate of oxidation of DL-dopa. RESULTS: The levels of tyrosinase activity in the acidum vitamin A group were significantly greater than those of the control group (P < 0.01). CONCLUSION: Tyrosinase activity can be increasingly induced by acidum vitamin A. PMID- 11780468 TI - Novel chromosomal alterations detected in primary nasopharyngeal carcinoma by comparative genomic hybridization. AB - OBJECTIVE: To gain a better understanding of genetic changes in Cantonese nasopharyngeal carcinoma (NPC). METHODS: Comparative genomic hybridization (CGH) was performed on 17 primary nasopharyngeal carcinomas. RESULTS: A novel copy number gain an chromosome 4q and loss of chromosome 1p were found at a high frequency (> 50%). CONCLUSIONS: Current analysis revealed a comprehensive profile of the chromosomal regions showing gain of chromosomes 4q, 12q, and 1q as well as loss of chromosomes 1p, 3p, 11q, 14q, 15q, 13q, Xq, 9q, 10p, 10q, and 16q. Frequently altered loci may encode oncogenes or tumor suppressor genes involved in the development of primary NPC. PMID- 11780469 TI - Genetic analysis of wild-type hepatitis A virus strains. AB - OBJECTIVE: To clarify the distribution of hepatitis A virus (HAV) genotype in geographical regions of China. METHODS: Seventeen representative HAV strains were isolated from the stool or serum of hepatitis A patients in different geographical regions. Viral RNA was recovered from stool or serum by proteinase K digestion and phenol-chloroform extraction, followed by ethanol precipitation prior to reverse transcription and polymerase chain reaction (RT-PCR) amplification. The nucleotide sequences of VP1/2A junction region were tested by using a direct sequencing technique. RESULTS: A pairwise comparison of sequences within 168 bases at the VP1/2A junction revealed that all the sequences clustered within genotype I. About 53% of strains clustered in genotype I B, with less than 6% variability; while the others clustered in genotype I A, with less than 5.3% variability. Sequence homology between genotype I A and I B varied from 88.7% to 92.3%. CONCLUSION: Epidemic or sporadic HAV strains in China may belong to HAV genotype I A or I B. Epidemiologically related strains may be identical or closely related in sequence. PMID- 11780470 TI - Clinical and genetic features of variegate porphyria in a Chinese patient. PMID- 11780471 TI - Short-term complete remission of a patient with human T lymphotropic virus type-1 associated adult T-cell leukemia/lymphoma with pancytopenia by sequential high dose methylprednisolone and cyclosporin A. PMID- 11780472 TI - Spontaneous perforation of the rectosigmoid colon: a report of 2 cases. PMID- 11780473 TI - Comments on "Hepatic radioembolization with yttrium-90 glass microspheres for treatment of primary liver cancer" by Cao et al, Chin Med J 1999; 112: 430-432. PMID- 11780474 TI - [Comparative study of technique of laser welding ceramo-alloy by different gap distance]. AB - OBJECTIVE: To investigate the quality of laser welded non-precious base alloy by different gap distance and its clinic probability. METHODS: Laser welded ceramo alloy CW-PA specimens by different gap distance of 0.0 mm, 0.25 mm, 0.5 mm, Tested joined sample's UTS, microhardness; took SEM examination on its tensile fracture surface and metallographic examination on longitudinal cross section. RESULTS: The study showed that UTS of Laser welded CW-PA by different gap distance of 0.0 mm, 0.25 mm, 0.5 mm is (446.05 +/- 82.50) MPa, (485.97 +/- 62.35) Mpa, (503.32 +/- 65.79) MPa respectively, approach to original rod (421.53 +/- 21.78) MPa (P > 0.05). Microimage at tested samples of gap distance at 0.0 mm, 0.25 mm are good. CONCLUSION: It revealed that 1. Laser welding specimen should be contacted as close as possible 2. The gap distance should be less than 0.5 mm, 0.25 mm is better, and easy to handle. PMID- 11780475 TI - [Analysis and comparison of dental arch symmetry between different Angle's malocclusion categories and normal occlusion]. AB - OBJECTIVE: To analyze and compare dental arch symmetry between different Angle's malocclusion categories and normal occlusion. METHODS: 300 subjects were divided into four different malocclusion groups and normal occlusion group. Data points representing the dental arches on the casts were precisely marked by YM-2115 three Dimension Measuring Machine. Arch forms were fitted with conic sections, and then dental arch symmetry was analyzed by rotation angle. RESULTS: There were no absolute symmetric dental arch, and the direction of asymmetry was unsteady. In normal occlusion, dental arch was generally symmetric, but there was asymmetry in a very small degree. As to malocclusion, the frequency and degree of dental arch asymmetry were higher than that of normal occlusion, and the lower arch showed more asymmetry than the upper arch except ClassIII. The frequency of asymmetry in ClassII2 and ClassIII groups was higher than that in other malocclusion groups. CONCLUSION: The frequency and degree of dental arch asymmetry were different in different malocclusion groups. PMID- 11780476 TI - [Surgical treatment of cervical lymph nodes in 301 patients with oral squamous cell carcinoma]. AB - OBJECTIVE: To evaluate cervical lymph metastases and its surgical treatment of oral carcinoma with regard to primary location and TNM classification. METHODS: 301 previously untreated patients were included in the follow-up study to calculate the rate of histopathologically positive lymph metastasis and the rate of recurrences in untreated necks and after FND (functional neck dissection). RESULTS: Lymph node pathologic positive rates were N0 7.4%, N1 14.7%, N2 76.2%. Recurrences occurred in 32.1% untreated necks and 14.7% necks after FND of carcinomas of tongue, buccal, lower-gingiva and oral floor, while rarely in necks of carcinomas of palate and upper-gingiva. CONCLUSIONS: TNM classification is useful to estimate lymph metastasis. Application of elective neck dissection needs to expand in carcinomas of the above four sites. It should be careful when choose FND. PMID- 11780477 TI - [A preliminary report of cleft palate repair by rotation and advancement of full thickness soft palate]. AB - OBJECTIVE: To introduce a new method of functional cleft palate repair. METHODS: Square flap A and triangular flaps B, C, D were designed on the each sides of defect at soft palate. They were advanced and rotated, each flap was inserted to the opposite side and then sutured. The lavator veli (LV) muscle was detached and sutured to reconstruct the steady LV muscle sling. RESULTS: This method was applied in 37 cases with satisfactory results of extending the soft palate, forming the dynamic soft palate muscular sling, and achieving velopharyngeal closure (VPC) 31 cases were flowed-up for half year to 2 years, the effects of operation are stable. CONCLUSIONS: This method not only close the cleft but also restore the soft palate's function of elevating and pushing back to achieve the ideal VPC. PMID- 11780479 TI - [An experimental study of tooth mesial migration]. AB - OBJECTIVE: To study the mechanism of tooth mesial migration with animal experiment. METHODS: The upper and lower first molars of Wuzhishan miniature pigs were used as experimental teeth. The mesial migration of experimental teeth was calculated and analysed by measuring the models. Fluorescent mark was used and analysed by injecting tetracycline and xvlenol orange, and histological changes were analyzed. RESULTS: The lower teeth migrate mesially 0.14 mm and 1.21 mm during 16 weeks, and the upper teeth migrate mesially 1.36 mm and 2.08 mm during 24 weeks. The distal alveolar bones of experimental teeth had fluorescent bands; alveolar bones of teeth without antagonist teeth reconstructed in vertical direction; the distance between fluorescent bands of lower experimental teeth without antagonist teeth was wider than that of teeth with antagonist teeth. The fluorescent bands formed in both mesial and distal cementum. CONCLUSION: The results don't support the point that transseptal fibre or force of molar eruption makes teeth migrate mesially; the mesial migration of teeth is related with the reconstruction of alveolar bones and the stress distribution in the bones. PMID- 11780478 TI - [Mechanisms of bone repairment in periapical diseases: studies on adjusting bone metabolism with calcium hydroxide in vitro]. AB - OBJECTIVE: To provide experiment evidence for clinical practice and for further exploration on mechanism and medicinal control of periapical diseases. METHODS: The culture model of neonatal mouse calvariae which has the similar biological activity to alveolar bone was established in vitro to observe the influence of calcium hydroxide on osteo-activity. RESULTS: The results showed that calcium hydroxide with proper concentration at organ culture level could enhance osteoblast ALP secreting activity, and increased the tendency of bone formation. At the same time, the concentration of inorganic PO4(3-) in culture medium also had significant changes. CONCLUSIONS: The mechanism of calcium hydroxide promoting repairment of bone tissues is not only by providing rich Ca2+ and alkaline environment mineral deposition, but also by stimulating calcification enzyme activity of osteoblast. Meanwhile, increased PO4(3-) concentration might improve the mineralization environment, which causes mineralization easily. PMID- 11780480 TI - [Detecting the level of Actinobacillus actinomycetemcomitans leukotoxin]. AB - OBJECTIVE: To detect the level of Actinobacillus actinomycetemcomitans (Aa) leukotoxin and distinguish the highly and the minimally toxic strains. METHODS: The polymerase chain reaction (PCR) assay was used to detect the difference of the nucleotide sequence of Aa leukotoxic promoter. 68 Aa isolates were examined, including 17 serotype b, 42 serotype c and 9 serotype a strains. The positive control strains were the highly toxic strain JP2 and 7 minimally toxic strains such as ATCC43717; the negative control strains were 12 other species of reference strains. RESULTS: The PCR fragments of JP2 was about 492 bp and that of the other Aa reference strains and 68 clinical isolates were 1,022 bp. PCR products not found in 12 other species. CONCLUSION: All of the 68 clinical isolates were minimally toxic strains. PMID- 11780481 TI - [Anatomic, sialographic, histologic and ultrastructural studies of normal parotid gland of the miniature pig]. AB - OBJECTIVE: To investigate the morphology of normal parotid gland of the miniature pig (minipig). METHODS: Anatomic, sialographic, histologic and ultrastructural studies of parotid glands were performed in 11 Chinese experimental minipigs. RESULTS: Sialograms showed a long main duct and a triangular shape gland. All branching ducts extended from the inferior-posterior of the main duct. No necessary glands were found. Typical serous acini were found microscopically. CONCLUSIONS: This study provides basic structural information of the parotid gland of the minipig. It is considered that minipig is a useful animal model in the investigation of parotid gland diseases. PMID- 11780482 TI - [Histopathological study of temporomandibular joint in early stage of polyarthritis rats]. AB - OBJECTIVE: To furnish an experimental basis of the early effects of rheumatoid arthritis (RA) on the temporomandibular joint (TMJ) by observing the histopathological changes of TMJ in the early stage of polyarthritis (PA) rats. METHODS: The animal model of PA was established by injecting Freund's complete adjuvant (FCA) into rats. The histopathological changes of the rats' ankle joint and TMJ were studied. RESULTS: (1) The paw volume and the articular index of PA rats increased significantly, and symptoms of pronounced inflammation were present in the ankle joint specimens, which included proliferation of the synovium, infiltration with inflammatory cells, erosion into the articular cartilage and bone, and inflammatory exudation into the articular cavities. (2) The histopathology of TMJ of PA rats showed pronounced proliferation of the synovium cells, some lytic collagenous fibers and degenerative chondrocytes in the condyles, and exudated protein and desquamating cells in the articular cavities with some fibrinous adhesions. CONCLUSION: Pronounced inflammation occurs in bilateral TMJ in early stage of PA rats. The examination, protection and treatment of TMJ for RA patients should be taken into account in the early stage. PMID- 11780483 TI - [Expression of p53 protein during 4NQO-induced lingual carcinogenesis in two strains of rats]. AB - OBJECTIVE: To investigate p53 protein expression during lingual carcinogenesis in two strains of rats. METHODS: Dark-Agouti (DA) and Wistar/Furth (WF) rats were administrated with 4-nitroquinoline 1-oxide (4NQO) in drinking water and expression of p53 was studied using experimental materials obtained at 2, 4, 8, 12, 16, and 26 weeks of 4NQO treatment. RESULTS: Epithelial clusters of p53 positive cells appeared earlier and more in numbers in DA rats than in WF. A marked increase of p53+ clusters in DA rats was noted at later stages of the experiment, whereas those in WF rats appeared to be unchanged. CONCLUSIONS: These results suggest that there may be genetically determined variations in the p53 response to 4NQO between DA and WF rats, and these differences may contribute to their contrasting susceptibility during lingual carcinogenesis. PMID- 11780484 TI - [A preliminary study of laser Doppler technique in determining dental pulpal blood flow]. AB - OBJECTIVE: To investigate the possibility of using laser Doppler flowmetry to study dental pulpal blood flow. METHODS: The pulpal blood flow of 80 healthy maxillary incisors of 20 volunteers and 15 teeth with necrotic pulp of 11 patients were determined by JI-200 Laser Doppler Flowmetry. The pulpal blood flow of 16 teeth with deep caries were measured before and after treatment. RESULTS: There were no obvious difference of the pulpal blood flow values between the right and the left part, neither the male and the female. Maxillary central incisors had a slightly greater pulpal blood flow values than maxillary lateral incisors. The flow values from 15 teeth with necrotic pulp or pulpless teeth were significantly lower than that from the control teeth. Before therapy the values from 16 deep caries teeth were all higher than that from the control teeth. After therapy, most (15/16) of those values decreased to normal in three days. The value of one tooth with deep caries remained high, and one week later, the pulp became necrosis. CONCLUSION: Laser Doppler flowmetry has great potentialities in the study of pulp blood flow, and deserves more concerns. PMID- 11780485 TI - [The dynamics of pH, free calcium and total proteins in root plaque fluid and their relationships to the cariogenic potential]. AB - OBJECTIVE: To enhance knowledge of root caries by analysis of the dynamics of dental plaque fluids on root surface and their relationships with the caries history. METHODS: The pH, free calcium and total proteins of dental plaque fluids on sound root surfaces were analyzed before and after the sucrose challenge. Subjects were either root caries-free (RCF) or caries-positive (RCP). RESULTS: After a sucrose challenge, the pH of plaque fluids dropped significantly and the concentration of free calcium increased significantly. There were no statistical differences in pH (RCF group 6.24 +/- 0.74, RCP group 5.96 +/- 0.70) and free calcium [RCF group (0.60 +/- 0.46) mmol/L, RCP group (0.89 +/- 0.54) mmol/L] between RCF and RCP group before sucrose challenge. Following sucrose exposure, pH (5.14 +/- 0.19) and free calcium [(1.73 +/- 0.74) mmol/L] in RCP group were significantly lower than RCP group [(pH 5.28 +/- 0.16), free calcium (2.73 +/- 1.25) mmol/L]. No interrelationship has been found between the amount of total proteins and free calcium. Components (contents, change trend) in root plaque were strongly related to that in coronal plaque. CONCLUSIONS: The process of root caries may be consistent to coronal caries regarding to the acid production of bacteria after a sucrose challenge. Plaque compositions show a stronger cariogenic potential in RCP group. PMID- 11780486 TI - [The effect of orthognathic surgery on temporomandibular joint function]. AB - OBJECTIVE: To prospectively investigate the signs and symptoms of TMJ in patients undergoing different orthognathic operations with rigid or non-rigid internal fixation. METHODS: The Helkimo index was used to analyze the anamnestic (Ai) and clinical (Di) data of 46 one-year postoperative cases being performed mandibular ramus osteotomies combined with other operations, and compared with preoperative data to analysis the changes of TMJ symptoms. RESULTS: The changes of the Ai and Di data were not significant. Postoperative in the four clinical indices, only the joint tenderness indice was significantly different from preoperative. Despite there were decreases of maximal opening of mouth, maximal protrusion, they were only 1% lower than preoperative data and had no clinical significance. The percentage of TMJ to develop after bimaxillary operation was not different from only mandibular operation. There was no significant difference as compared between different operations and fixation methods. CONCLUSIONS: The change of TMJ symptoms and signs after orthognathic surgery was not significant. Compared with each other the various surgical procedures (bimaxillary or only mandibular, BSSRO or BIVRO, RF or NRF) were not found any difference about the effect on the TMJ. PMID- 11780487 TI - [The repairment of the condylar cartilage defect by transplantation of chondrocytes embedded in the collagen membrane]. AB - OBJECTIVE: To study the effect of repairing the defect on the condylar articular cartilage by chondrocyte transplantation. METHODS: A full-thickness defect was made in the condylar articular cartilage of the adult rabbit. The isolated condylar chondrocytes of the rabbits cultured in vitro for one week were embedded in the collagen membrane, and then transplanted into the defect. RESULTS: The defects of the condylar articular cartilage were repaired with cartilage tissue. CONCLUSIONS: The defect of the condylar articular cartilage could be repaired with articular cartilage-like tissue by transplantation of the condylar chondrocytes. PMID- 11780488 TI - [Occlusal contact force and stress analysis of molars with vertical root split]. AB - OBJECTIVE: To study the induction of vertical root split by occlusal force. METHODS: 1. The occlusal contact force was studied in 34 cases (39 teeth) by photocclusion. 2. The stress analysis for the first mandicular molar was studied by three-dimensional definite element. RESULTS: 1. The occlusal contact force didn't distribute balancedly in 26 cases (31 teeth) and the suffering teeth bore greater force. 2. The bucco-lingual central line of the mesial root canal wall underwent greater tensile stress when tooth bore load with 30 degrees angle to axis, or buccal-lingual lateral load or logitudinal occlusive load on the masial or distal cusp. CONCLUSION: The vertical root split of molar is associated with greater occlusal force and the stress that concentrated on the buccolingual central line of the mesial root wall for a long time. PMID- 11780489 TI - [Noxious stimulation-induced morphological changes of nitric oxide synthase positive neurons in the tongue of rats]. AB - OBJECTIVE: To explore noxious stimulation-induced morphological changes of nitric oxide synthase (NOS) positive neurons in the tongue. METHODS: The histochemical method of reduced nicotinamide adenine dinucleotide phosphate(NADPH)-diaphorase activity was used. RESULTS: NOS positive neuron bodies in the tongue were obviously enlarged, the staining intensity increased and nerve fibers became thicker after injury. At the body and tip of the tongue, near the body cells of NOS positive neurons deeply stained fine granular particles were seen, and structures of plum blossom form were seen along the route of the nerve fiber extending all the way to the terminal. NOS positive nerve fibers in the striated muscles and around the gland in the tongue root became thicker, and bead structures were seen in some of the fibers. CONCLUSION: NOS positive neurons of the tongue, when noxiously stimulated, are inflicted with pathological changes, which suggest that nitric oxide might play a role in the transmission and control of the message related to pathological lesions. PMID- 11780490 TI - [The study of a computer aided artificial teeth arrangement of complete denture]. AB - OBJECTIVE: To develop a system of computer aided complete denture design (CACDD). METHODS: After 3 dimensional measurement, data process and making model of a edentulous model, artificial teeth and the maxillomandibular bite plate, on the position of centric relation, the artificial teeth were arranged according to the principle and demand of the complete denture's teeth arrangement. The relation of teeth and occlusion were adjusted by Affine and Projection transformation. RESULTS: (1) The maxillomandibular visual base on the position of centric relation were made, its mathematics model is B-Spline curve surface of the double third power. (2) The artificial teeth arrangement and 3 dimensional show of the complete denture were achieved. CONCLUSION: This system can provide a feasible tool for a computer aided complete denture design and teaching. PMID- 11780491 TI - [The research of a multimedia consultative system for prosthodontics]. AB - OBJECTIVE: To study how to develop the consultative multimedia system for prosthodontics facilitating the communication between the dentists and patients, using multimedia techniques. METHODS: The Founder Author Tools V2.1 was used to develop the consultative system in the Pwin95/98 environment. Many forms (such as the articles, pictures, sound and video) of the prosthodontic knowledge were edited in this system. RESULTS: The consultative multimedia system for prosthodontics was developed, and there were three main parts of the system: (1) the background of medical departments, (2) introductions of the medical specialists (including their photos and working time), (3) introducing the common acknowledge of prosthodontics. CONCLUSION: The visualization of the prosthodontic problems consulted by patients frequently can facilitate the communication between the dentists and patients and spare visit time. This system are welcome by the patients. PMID- 11780492 TI - [Miniplate osteosynthesis of mandibular fracture]. AB - OBJECTIVE: To evaluate the reliability and effectiveness of miniplate osteasynthesis in mandibular fractures. METHODS: 51 mandibular fractures in 31 cases treated with titanium miniplate osteosynthesis was analysed. RESULTS: No infection was found 28 cases had satisfied occlusion, 2 cases had unfavourable local malocclusion. The mouth opening of 28 cases were over 37 mm, only 2 cases under 37 mm 3 months postoperatively. CONCLUSIONS: The miniplate osteosynthesis has the advantages over conventional intermaxillary fixation and wire fixation. PMID- 11780493 TI - [A clinicopathologic study on membranous basal cell adenoma]. AB - OBJECTIVE: To investigate the clinicopathologic features and behaviour of membranous basal cell adenoma. METHODS: Twelve cases with membranous basal cell adenoma of salivary gland were analysed clinicopathologically. RESULTS: The tumors were composed of epithelial islands of various sizes and shapes. Its histologic finding was characterized by palisading of peripheral cells and excessive hyaline basal membrane. Four cases had co-existing dermal cylindromas of the scalp. In 8 cases, the tumors demonstrated multiple origin. One case showed malignant transformation and cervical lymph node metastasis. CONCLUSIONS: The differential diagnosis involved the solid variant of basal cell adenoma, basal cell adenocarcinoma, solid subtype of adenoid cystic carcinoma and basal squamous cell carcinoma. Total parotidectomy rather than superficial parotidectomy is suggested to avoid the recurrence of the tumor. A close follow up after treatment is necessary. PMID- 11780494 TI - [Experimental study on the influence of Gynostemma pentaphyllam Mak upon point mutation of Ha-ras oncogene in blocking leukoplakia from canceration]. AB - OBJECTIVE: To study the influence of Gynostemma pentaphyllam Mak (GP) upon point mutation of Ha-ras oncogene the molecular mechanism of GP in blocking canceration, and the relationship between Ha-ras oncogene and canceration of leukoplakia. METHODS: DMBA induced carcinogeneses of the buccal pouch mucosa of the hamsters were divided into leukoplakia model group(LKG) and GP treated group(GPG). Point mutation (codon 61) of Ha-ras oncogene was detected by PCR-SSCP in both groups. RESULTS: The mutation incidence of LKG was 22.96%, while the mean incidence of GPG was 7.59% (The incidences of C20-OH group, glucoside group and aglucon group were 5.32%, 6.25% and 11.00% respectively). When treated with DMBA for 4 to 8 weeks, the mutation incidence of LKG ranged from 11.10% to 40.00%, while GPG ranged from 0 to 10.70%. CONCLUSIONS: GP has outstanding cancer blocking effect chiefly affected by free C20-OH. Mutation of Ha-ras oncogene plays an important role in leukoplakia canceration. PMID- 11780495 TI - [Induction of fluoride-resistant mutant of S. mutans and the measurement of its acidogenesis in vitro]. AB - OBJECTIVE: To induce fluoride-resistant mutant of S. mutans in vitro and find out the differences of cariogenicity between them. METHODS: Fluoride-resistant strain Ingbritt-FR was obtained by subculturing S. mutans Ingbritt to TSA and TSB containing different concentrations of fluoride. Lactic production and terminal pH of media were measured by gas chromatography method. RESULTS: 1. The stable fluoride-resistant mutant of S. mutans Ingbritt had been induced successfully in vitro; 2. Lactic production of Ingbritt-FR was significantly more than its parent strain at various initial pH values with 0.5 and 5.0 mmol/L fluoride whereas when no fluoride existed, there were two situations: the acid production was more than S. mutans Ingbritt at initial pH above 5.0 while the result was opposite when pH was 5.0 and below. CONCLUSION: The fluoride-resistant strain Ingbritt-FR had a stronger cariogenic potential than its parent strain S. mutans Ingbritt in physiological plaques. PMID- 11780496 TI - [An experimental investigation between osseointegration and stability of implants used as orthodontic anchorage in dogs]. AB - OBJECTIVE: To investigate the relation between osseointegration and stability of three kinds of implants used as orthodontic anchorage in dogs. METHODS: HA coated, titanium coated, and uncoated titanium implants were inserted into each femur of two dogs. After heal period of three months, the orthodontic force of 200 g was applied by means of Ni-Ti springs, which were connected to the two adjacent implants, for two months. The position change of implants was measured and calculated. The shear bond strength of interface between implant and bone was measured with push-test. The interface was observed with scanning electronic microscope. RESULTS: The distance changes of HA-coated, T-coated and uncoated groups were (-0.50 +/- 1.78) mm, (-0.05 +/- 1.76) mm and (0.29 +/- 1.77) mm, respectively, which showed no statistical difference. The shear strength values were (2.88 +/- 0.55) MPa, (1.89 +/- 0.81) MPa and (2.14 +/- 0.49) MPa, respectively. HA-coated implant contacted with bone closely and the bond strength was the highest. The other two implants were found no significant difference in bond strength. CONCLUSION: The osseointegration was found at the interface among all three kinds of implants and bone and no displacement was found during application of clinical orthodontic force. PMID- 11780497 TI - [Antitumor effect of radiation combined with tumor draining lymphocytes on human ACC-M cell in vitro]. AB - OBJECTIVE: To find whether there is any synergistic effect of radiation combined with interleukin-2(IL-2) activated tumor draining lymph nodes lymphocytes (DNL) from oral-carcinoma patients on high-lung metastatic salivary adenoid cystic carcinoma cell line(ACC-M). METHODS: Colony-forming test was used to investigate antitumor effect and analyzed using linear-quadratic(LQ) equation and single hit multi targets equation. RESULTS: The ratio of effect to targets was 25:1. The cytotoxicity of DNL was 49.06%. Radiation combined with DNL showed higher antitumor activity compared with radiation alone, alpha value, Dq and S2 were 0.7688 and 0.342 0; 1.5901 and 0.5995; 0.4481 and 0.1135 respectively(P < 0.05). CONCLUSIONS: It indicates that in initial region of survival curve, DNL significantly increased sublethal damage on ACC-M. PMID- 11780498 TI - [A one-year study on enzyme level in gingival crevicular fluid around osseointegrated dental implants]. AB - OBJECTIVE: To investigate the changes of gingival crevicular fluid(GCF) volume, aspartate aminotransferase (AST) and alkaline phosphatase(ALP) levels in GCF around dental implants during the first year after rehabilitation. And to explore the relationships between these changes and peri-implant inflammation as well as bone loss. METHODS: 26 Branemark implants in 12 adults were included in this study. Examinations were carried out in a total of 52 sites in preinsertion period and 3, 6, 12 months following rehabilitation. RESULTS: GCF volume, GCF AST, GCF-ALP were firstly increased and then fallen during the first year after rehabilitation. GCF volume, GCF-AST, GCF-ALP in sites with peri-implant mucositis were higher than those in health sites, and were increased with the severity of peri-implant mucositis. GCF volume, GCF-AST, GCF-ALP in sites with bone loss were significantly higher than those without bone loss. CONCLUSION: GCF volume, GCF AST, GCF-ALP could reflect peri-implant inflammation and bone changes to some degree. PMID- 11780499 TI - [Study of congenital velopharyngeal insufficiency and hypernasality]. AB - OBJECTIVE: To evaluate 27 congenital veloparyngeal insufficiency(CVPI) subjects and 6 normal articulation subjects with airflow pressure techniques. METHODS: A compare analysis was performed in two groups (CVPI subjects and normal articulation subjects) during speech production of /hemper/ and /papa/. RESULTS: There wasn't statistical significance between two groups in oral air pressure and velopharyngeal orifice areas, however, CVPI group differed significant in nasal airflow on the articulation of /hemper/ and /papa/. CONCLUSIONS: When the degree of CVPI subject's VP opening was small, hypernasality appeared to be related to duration of the opening-closing movements. PMID- 11780500 TI - [A quick way in isolation and amplification of mandibular condylar cartilage cell in vitro]. AB - OBJECTIVE: To establish a quick way in acquiring well differentiated mandibular condylar cartilage (MCC) cells with high viability in large scale. METHODS: Japan white rabbit MCC cells were harvested by enzymatic method. They were grown in a modified bioreactor culture system, which contained the cytodex-3 micro-carriers in the culture medium. Kinetic growth of MCC cells on DEAE-dextran micro-carrier was observed under phase contrast microscope and environmental scanning microscope respectively. RESULTS: MCC cells attached rapidly to the surface of micro-carriers, but their spreading was slow. A quick growth of these cells was observed when they fully spread onto the micro-carrier. The number of MCC cells increased 16.2 times compared with that of plating. CONCLUSIONS: Micro-carrier culture of MCC cells can yield a large quantity of cells within a short period of time that will be of benefit in banking MCC cells for reconstruction of impaired cartilage. PMID- 11780501 TI - [The study of tarnish induced by Actinobacillus actinomycetemcomitans serotype b (Aay4) on titanium and Ti-75 alloys]. AB - OBJECTIVE: To study the tarnish induced by Aay4 on titanium and Ti-75 alloys. METHODS: Pure titanium and Ti-75 alloys were machined into size of 10 mm x 10 mm x 1 mm in tablets(30 of pure titanium; 60 of Ti-75 alloys). Thirty specimens sampled randomly from Ti-75 alloy together with 30 specimens of titanium were subjected to chemical passivation treatment. 30 specimens of the pure titanium, depassivation Ti-75 alloy and passivation Ti-75 alloy were randomly divided into three groups (blank control group, media control group and inoculated media group) respectively, every group contains 10 specimens. Under the anaerobic conditions, the surfaces of the modified GAM media were inoculated with Aay4. The labeled specimens surfaces were then aseptically placed on top of the media surface for 10 weeks with one generation time per week. The specimens were removed after 10 weeks of incubation, immersed in 0.05% glutaradehyde solution to eliminate Aay4, rinsed with distilled water. After 2 weeks, the specimens were removed and observed visually or examined by MINOLTA CR-100 color apparatus. RESULTS: Visual evaluation: Aay4 caused significant tarnish on specimens exposed to inoculated media, all the specimens surface changed into yellow color. Color apparatus evaluation: this result showed that comparing with the blank control, media control has no influence on all the specimens L*a*b* values (P > 0.05). Aay4 caused significant tarnish on specimens exposed to inoculated media, the result showed that there was significant difference between media control group and blank control group with inoculated media group on all the specimens L*a*b* values (P < 0.05). CONCLUSION: Aay4 caused significant tarnish on pure titanium, depassivation Ti-75 alloys and passivation Ti-75 alloys by naked eyes and color apparatus, according CIE1976L*a*b* color system reading, the color of titanium and Ti-75 alloys changed from the yellow-green ranges to red-yellow ranges. PMID- 11780502 TI - [The anatomy of the pterygopalatine canal in relation to the Le Fort I osteotomy]. AB - OBJECTIVE: The most common site of hemorrhage in maxillary osteotomies is the posterior maxilla. Better understanding of the anatomy in this region may minimize possible vascular complications. The aim of the study is to investigate the anatomy of posterior maxilla and establish safety guidelines for the Le Fort I osteotomy. METHODS: Thirty dry human skulls were selected for direct measurement and analysis. RESULTS: Results showed that the average distance from the piriform rim to the descending palatine canal was 35.25 mm, the average distance from the zygo-alveolar ridge to the descending palatine canal was 25.41 mm, the average distance from the descending palatine canal to the central line was 16.68 mm, the average distance from the piriform rim to the central line was 12.87 mm. The angle between the line from the piriform rim to the descending palatine canal and the central line was 6 degrees 14'. CONCLUSIONS: The study is to provide further understanding of the posterior maxillary anatomy in relation to the bone cut design of Le Fort I osteotomy, and to create clinical safety guidelines in order to avoid damaging the descending palatine vessels. PMID- 11780503 TI - [Digital dental radiographic technique and its clinical application]. AB - OBJECTIVE: To investigate the digital dental radiographic technique and its clinical application. METHODS: One hundred and five dental films were taken in 88 cases with the digora digital radiographic system and studied. RESULTS: The digora system has more advantages than the conventional dental radiographic technique. The image plate was used instead of the films and shorten exposure time. It had high exposure tolerances and image processing functions. CONCLUSIONS: This new imaging system applied in the clinics and research work can play an important role in improving the diagnostics. PMID- 11780504 TI - [The effects of relieving space to stress distribution of mandibular implant supported overdenture]. AB - OBJECTIVE: To study the effects of relieving space to stress distribution of mandibular implant-supported overdenture under shocking loads. METHODS: 3-DFE method was used to make a comparative study of the effects of relieving space to stress distribution of the implant-supported overdenture under shocking loads. RESULTS: The application of stress relieving space can lower the stress peaks of the implants, periimplant tissue and the denture base. The highest stress of compression in lateral bone-implants interface reduced 52%. CONCLUSION: The application of stress relieving space can be helpful to protect implants, periimplant tissue and denture base. PMID- 11780505 TI - [The role of bcl-2 and bax genes and programmed cell death in the temporomandibular joint development]. AB - OBJECTIVE: To evaluate the roles of bcl-2, bax gene and programmed cell death(PCD) in the TMJ development. METHODS: PCD, expression of both mRNA and protein of bcl-2 and expression of bax protein were observed by Tdt-mediated dUIP nick end labeling (TUNEL), mRNA in situ hybridization and immunohistochemical staining in TMJ of SD rats during series prenatal and postnatal developmental periods. RESULTS: PCD was involved in condylar cartilage in development of different periods. The cells of PCD were mainly located in proliferative zone and the area between prehypertrophic zone and late hypertrophic zone. bcl-2mRNA was expressed with high levels in proliferative and prehypertrophic zones and very few matured chondrocytes expressed bcl-2. The expression of bcl-2 protein showed the same distribution as bcl-2mRNA, but gradually decreased in late hypertrophic zone, compared with strong expression of Bax throughout condylar cartilage. CONCLUSIONS: PCD of condylar cartilage is regulated by bcl-2 and bax gene, the number and site of PCD are attributed to the change of bcl-2 and bax gene, and bcl-2 is an important gene in maintaining survival of chondrocytes during the proliferation, differentiation and maturation. PMID- 11780506 TI - [Detection and effect of telomerase activity in oral mucosal squamous cell carcinoma]. AB - OBJECTIVE: To study telomerase activity in 20 oral squamous cell carcinoma(SCC), and 10 normal oral tissues and 9 oral SCC and 9 adjacent normal tissue. METHODS: A modified PCR-based telomeric repeat amplification protocal assay(TRAP) was used. RESULTS: The telomerase activity was significantly higher in SCC than that of normal mucosa, and than that of adjacent tissue as well. CONCLUSIONS: These findings indicated that telomerase activation might be a critical step in the formation and development of cancer. PMID- 11780507 TI - [Clinical studies on the use of hyperbaric oxygen in replantation of young permanent teeth]. AB - OBJECTIVE: To investigate the treatment effects of hyperbaric oxygen(HBO) in replantation of young permanent teeth. METHODS: A total of 138 luxation injuries to young permanent teeth undergoing treatment. The teeth were replanted and then divided into 2 groups. The HBO group was exposed to 0.25 MPa pure oxygen 40 x 2 minutes each day for 10 days continuously while the control group were compared. RESULTS: The total effective rates of the HBO group and the control group were 97.26% and 70.77% respectively, and showed significant difference (P < 0.05); respective frequencies of missing tooth after 1 year were 1.37% and 18.46%, and provided a statistical significance (P < 0.001). CONCLUSION: HBO used in replantation of luxated young permanent teeth could promote the recovery of periodontal membrane, pulp, and prevent resorption of root. PMID- 11780508 TI - [Geometric relationship of axial crown contour and gingiva contour of normal second mandibular premolars]. AB - OBJECTIVE: To investigate the relationship of axial crown contour and surrounding healthy gingiva contour. METHODS: Mandibular second premolars were selected as the object of study. Three cross-sections were made through crown and gingiva of the model tooth. Curve functions of axial buccal crown and gingiva contour of each section were acquired by means of curve fitting, and the angle of emergence profile was calculated, which represents the degree of undercut. RESULTS: There is unique relationship between axial crown and gingiva contour individually. This character of tooth is similar to its contralateral tooth. The emergence profile angles are in the range of 40 degrees-110 degrees, 84.1% of the angles are in range of 70 degrees-110 degrees, 15.9% in 40 degrees-70 degrees, that is to say natural teeth are inclined to be of less undercut. CONCLUSION: The geometric relationship between crown contour and gingiva contour is so characteristic that contralateral tooth should be the only guidance to replace lost tooth. PMID- 11780509 TI - [The effect of prednisolone on the regeneration of condylar cartilage of the rabbit]. AB - OBJECTIVE: To investigate the effect of the prednisolone on the condylar cartilage regeneration. METHODS: A full-thickness defect without penetrating the subchondral compact bone was made in the condylar cartilage of the adult rabbits, and prednisolone(25 mg) was applied locally. The reparative tissue was observed histologically and histochemically. RESULTS: The compact bone in the area of the defect of the condylar cartilage showed hyperplasia, and the defect was filled with compact bone at the end of twelve weeks. CONCLUSIONS: Prednisolone is able to repair the defect of the condylar cartilage. PMID- 11780510 TI - [The role of MHC molecules on OSCC cells in the induction of autologous cytotoxic T lymphocytes]. AB - OBJECTIVE: To investigate the role of major histocompatibility complex(MHC) molecules in the induction of cytotoxic T lymphocyte(CTL) from oral squamous cell carcinoma. METHODS: 1. The treated autologous tumor cells served as stimulating cells, on which the MHC mAb was used to block the HLA-ABC and/or HLA-DR antigens. The specific cytotoxicity of CTL induced by stimulating cells and the level of released TNF-alpha were then detected. 2. By blocking the HLA-ABC and/or HLA-DR antigens on target cells, the inhibition effect of MHC mAb on CTL cytotoxicity induced by autologous stimulating cells (not treated with mAb) was measured. RESULTS: 1. The cytotoxicity induced by stimulating cells in experimental groups was significantly lower than that of the control group. The successive order was: the DR antigen positive stimulating cell group > ABC antigen positive stimulating cell group > both ABC and DR antigen negative stimulating cell group. The specific TNF-alpha released by CTL was completely blocked by anti-ABC mAb. 2. The average inhibition rate by mAb on cytotoxicity of CTL was: 52%, 27% and 72% by anti-ABC mAb, anti-DR mAb, and anti-ABC mAb plus anti-DR mAb respectively. CONCLUSION: Both MHC-class I and class II antigens on OSCC cells play an important role in inducing CTL. PMID- 11780511 TI - [A preliminary study of viral cross-transmission in dentistry]. AB - OBJECTIVE: To research the viral cross-transmission of a DNA virus (HBV) and a RNA virus (HCV) in dentistry. METHODS: Five plans were designed to sterilize the oral instruments that had been infected with HBV or HCV positive serum. HBsAg, HBV-DNA, anti-HCV, HCV-RNA were detected before and after sterilization. RESULTS: All methods could effectively clean the specific proteins (HBsAg/anti-HCV) and nucleic acids (HBV-DNA/HCV-RNA) of the infected virus. CONCLUSION: The instruments which have been sterilized should not be the main way of the cross transmission of virus in dentistry. PMID- 11780512 TI - [Effect of fixed appliance on periodontal status of patients with malocclusion]. AB - OBJECTIVE: To determine if the fixed appliance will affect the periodontal health. METHODS: Sixteen patients with malocclusion were randomly selected. One week before the fixed appliance placement, plaque index (PLI), bleeding index (BI), pocket depth (PD) and subgingival plaque were assessed. The observed value was served as the baseline records. RESULTS: After the fixed appliance placement, significant differences were found in PLI, BI, PD and these values were significantly greater than the baseline. Subgingival microfloral shifted to a more disease-inducing microflora and there was a statistically significant increase in spirochetes and fusiform. CONCLUSION: Fixed appliance placement will affect the periodontal health. Therefore, it is very important to strengthen the oral hygiene instruction to the people who receive the treatment of fixed appliance. PMID- 11780513 TI - [The effects of EGF, TGF-beta and insulin on the growth of rabbit's skeletal muscle satellite cell]. AB - OBJECTIVE: To investigate the effects of epithelium growth factor (EGF), transforming growth factor-beta(TGF-beta) and insulin on the growth of cultured rabbit's skeletal muscle satellite cells. METHODS: After treatment with EGF, TGF beta and insulin, MTT method was used to study the proliferation of the cells. RESULTS: EGF and insulin could promote the growth of the satellite cells more significantly than that of TGF-beta. CONCLUSION: It implied that there was a close relationship between the effects of three agents and the regeneration of injured muscles. This kind of positive effect appeared in a dose- and time dependent manner. PMID- 11780514 TI - [The induction of transforming growth factor-beta 1 in reparative process of mouse experimental alveolar bone defect]. AB - OBJECTIVE: To study the induction of transforming growth factor-beta 1(TGF-beta 1) in reparative process of mouse experimental alveolar bone defect. METHODS: Alveolar bone defect were made in 20 mice at 1/1 region. In twelve mice (experimental group), the defect was filled with gelatin sponge infiltrated by TGF-beta 1 solution; in eight mice (control group), the defect was filled with gelatin sponge. The peripheral tissue coating alveolar bone defect was harvested for histopathologic study after 1 week, 2 weeks and 1 month, 3 months. RESULTS: The main histopathologic changes were: 1. experimental group: inflammatory cell infiltration (1W); inflammatory cell disappearance, fibroblast and capillary tachyauxesis, osteoid tissue and small amount neoformative bone tissue appearance (2 W); fibrous tissue decrease, neoformative bone tissue enlarging and maturity(1 3 M). 2. Control group; inflammatory cell infiltration (1W); inflammatory cell disappearance, fibroblast and capillary tachyauxesis (2W); osteoblast appearance around bone defect (1M); small amount neoformative bone tissue around bone defect. CONCLUSION: TGF-beta 1 can induce alveolar bone regeneration. PMID- 11780515 TI - [The effects of the enameloplasty on the penetration and adaptation of sealant]. AB - OBJECTIVE: To study the mechanism of enameloplasty technique by observing penetration and adaptation of sealant. METHODS: 60 extracted molars were selected and divided into three groups: pits and fissures of the samples in group A were prepared with bur(EST); those in group B were cleaned with cup-shaped brush(CST); group C, as control. RESULTS: The penetration of EST was (83.75 +/- 13.11)%, CST was (55.30 +/- 11.98)%. The presence of defects between sealants and inclines of cusp of EST and CST were 7.32% and 19.05% respectively, and between sealants and lateral walls of fissures were 16.07% and 38.93%. CONCLUSION: The penetration and adaptation of EST was superior to CST. PMID- 11780516 TI - [A study of chemo-hand instrument removal of caries in vitro]. AB - OBJECTIVE: To study the efficiency of chemo-hand instrument removal material. METHODS: The effect on caries removal of N-monochlorochloraminobutyric acid and the electrical dental instrument was detected by the caries detection, microscope and SEM. RESULTS: The positive for the caries detection and residual caries were zero in both groups. CONCLUSION: The effect on caries removal of N monochlorochloraminobutyric acid is almost the same as the control. PMID- 11780517 TI - [The influence of malocclusion on self-esteem and personality of college student]. AB - OBJECTIVE: To study the relationship among the different malocclusions and self esteem and personality. METHODS: Two hundred and forty college students with normal occlusion and different types of malocclusion were classified into four groups(class I, class II, class III and normal) by Angle's classification, Sixty students in each group. The first three groups had been divided into three subgroups respectively by IOTN: mild, moderate and severe, twenty students in each subgroup. Each subject was assessed by using the body-esteem scale (BES) and the Eysenck personality questionnaire (EPQ). RESULTS: (1) the mean score on facial appearance subscale in BES of the normal group is significantly higher than that of moderate and severe subgroups in class II and class III groups; (2) the mean T score on E subscale in EPQ of the normal group is significantly higher than that of severe subgroups in class II and class III groups, and the mean T score on N subscale in EPQ of the normal group is significantly lower than that of severe subgroups in class II and class III groups; (3) There is a positive correlation between the mean score on facial appearance subscale in BES and the mean T score on E subscale in EPQ and a negative correlation between the mean score on facial appearance subscale in BES and the mean T score on N subscale in EPQ. CONCLUSIONS: (1) The students with moderate and severe class II and class III malocclusion have lower self esteem about their facial appearance than normal students; (2) The trends of introverstion and astatic emotion are higher in students with severe class II and class III malocclusion than in normal students; (3) The higher self esteem about his (or her) facial appearance, the higher trends of extroversion and statical emotion he(or she) has; the lower self-esteem about his (or her) facial appearance, the higher trends of introversion and astatic emotion he (or she) has. PMID- 11780518 TI - [The progress and discussion of treatment of Class II malocclusion]. PMID- 11780519 TI - [Application of distraction osteogenesis in functional mandibular reconstruction]. AB - OBJECTIVE: To study the application of distraction osteogenesis in mandibular functional reconstruction. METHODS: Three kinds of mandibular distractors were used in 6 cases who had different mandibular defects because of tumor resection. For two cases with defect of most part of ramus specially desinged distractors were used in order to keep the normal height of the ramus. In one case the trifoci distraction principles were used and a trifoci distractor was desinged. In three cases the vertical distractors made in Germany or China respectively were used. The average age of 6 patients was 31.5 years old (from 8 to 54). RESULTS: The mandibular lengthenings in 5 cases were fully successful according to the direction and distance desinged before distraction. In one case the trifoci distraction principle was applied and a proximal 23 mm mandibular defect was corrected successfully, however, the 23 mm distal mandibular defect had not corrected because the screws for fixation of the transport block was loosened. No infection and dysosteogenesis were happened in all cases. CONCLUSIONS: Distraction osteogenesis can successfully be used in mandibular functional reconstruction and has much more advantages than traditional techniques. The most favorable time for distraction osteogenesis in mandibular reconstruction is at the same stage of tumor resection. PMID- 11780520 TI - [The effects of distalization of upper molars in Class II malocclusion by pendulum appliance]. AB - OBJECTIVE: To study the mechanics of Pendulum appliance, and its effects on craniofacial and dentoalvaolar structure. METHODS: 16 class II malocclusion patients (13 females and 3 males) were selected as the subjects, aged from 9.3 to 22.8 years(13.6 on average). All the patients were treated with Pendulum appliance. The duration for distolization of upper molars was from 1 to 6 months(3.7 months on average). Cephalomatric analysis was used. RESULTS: 1. The upper molar was distalized by 3.59 mm per side with mainly tilting movement. 2. Incisors moved mesially by 3.28 mm per side (tilting movement). 3. Anterior overjet was increased by 1.56 mm after treatment and more than 6 mm space was created per side. 4. The upper molars extruded slightly by 0.69 mm. 5. The width of upper arch was increased by 2.03, 1.66, 1.10 mm at molar, premolar and canine region respectively. 6. The Pendulum appliance had less effects on craniofacial structure because of short treatment time. CONCLUSIONS: The Pendulum appliance can distalize the upper molars effectively without patients' active cooperation. However, it should be cautions in using the appliance because of its side effects on tilting of molars and mesial movement of incisors. PMID- 11780521 TI - [Treatment of Class II division 1 extraction cases by use of edgewise technique]. AB - OBJECTIVE: To treat class II division 1 extraction cases by means of Edgewise technique. METHODS: 27 skeletal class II division 1 malocclusion patients were extracted 2 upper first premolars and 2 lower second premolars, and treated by Edgewise principles and sequential force system. They aged from 11 to 20. The duration of orthodontic treatment was 25.5 months on average(22-28 months). RESULTS: The patients' profile was much improved; Molar relation changed from class II to class I relationship; Anterior overjet and overbite are normal; Good occlusal intercuspation is also achieved. The ANB angle was significantly changed from 5.6 degrees +/- 2.2 degrees to 3.2 degrees +/- 1.4 degrees; Z angle was altered from 60.8 degrees +/- 5.8 degrees to 76.4 degrees +/- 6.6 degrees; Distance of AO-BO was reduced from 6.8 +/- 2.4 mm to 3.2 +/- 1.1 mm. CONCLUSIONS: Edgewise technique is an effective method for treatment of class II division 1 extraction cases. PMID- 11780522 TI - [Clinical understanding and therapeutic analysis of multiloop edgewise archwire correction of Angle Class II malocclusion]. AB - OBJECTIVE: To use multiloop edgewise archwire (MEAW) to correct class II malocclusion and to analyse its therapeutic effects and principles. METHODS: 10 class II division 1 and 3 class II division 2 cases were treated with MEAW technique. RESULTS: Gratifying results have been achieved in all cases in a relatively short period of time. CONCLUSIONS: With full understanding of correcting principle of the archwire for class II malocclusion and active cooperation of the patient, the MEAW technique produces twice the result with half the effort. PMID- 11780523 TI - [Treatment of Class II division 1 malocclusions with single maxillary extraction orthodontics]. AB - OBJECTIVE: To investigate the effects, indications and clinical significance of single maxillary extraction orthodontics used for class II division 1 malocclusions. METHODS: 14 class II division 1 patients were treated by single maxillary extraction orthodontics, the cephalometric data before and after treatment were analysed by statistical methods. RESULTS: After treatment, 1. the angle 1-FH had decreased by 11.03 degrees and the angle 1-MP had increased by 3.07 degrees; 2. The mandibular length had increased by 3.30 mm; 3. the upper and lower lip were retruded by 2.65 mm and 1.64 mm respectively. Statistical significance (P < 0.001-0.05) was found between the means before and after treatment. CONCLUSIONS: Single maxillary extraction orthodontics is suitable for class II division 1 patients with less labial tipping of lower incisors and less lip protrusion. PMID- 11780524 TI - [Telomerase activity in rat tongue carcinogenesis]. AB - OBJECTIVE: To detect the telomerase activity in rat tongue cancer and precancerous lesions and to investigate the possibility of telomerase as oral cancer biological marker. METHODS: A total of 69 rat tongue carcinogenesis specimens induced by 4-nitroquinoline-1-oxide (4NQO) were examined for telomerase activity by PCR-telomeric repeat amplification protocol (TRAP) silver staining and ELISA. RESULTS: Sequential increase in telomerase activity in tongue carcinogenesis was found. The positive rate of telomerase in normal, HP, mmDP, sDP, ISC and SCC was 0.0%, 12.5%, 25.0%, 66.7%, 72.7% and 93.8%. CONCLUSIONS: Telomerase may be a tumor specific gene marker, and may play an important role in early diagnosis and treatment of oral cancer. PMID- 11780525 TI - [Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands]. AB - OBJECTIVE: To study factors influencing survival rate of adenoid cystic carcinoma (ACC) of the salivary glands. METHODS: One hundred and twelve cases were followed up for move than ten years and were studied to investigate factors influencing the survival rate of patients. Statistical analysis was performed using a computer program (Survcalc, John Wiley Co.). The data were statistically treated for survival curves according to the kaplan-meier method. The log rank tests were employed to assess the statistical significance of various groups. RESULTS: The age of the patients younger than 50 years old, early clinical stage, glandular/tubular histological type and tumor without nerve involvement had the best prognosis. Age of the patients older than 50 years old, ACC in the submandibular gland, advanced clinical stage (stage III and IV), solid histological type and tumor with nerve involvement had a poor prognosis. CONCLUSIONS: Age of the patients, tumour site, clinical stage, histological type and with or without nerve involvement are the important factors influencing the prognosis. PMID- 11780526 TI - [Management of severe maxillary deficiency through distraction osteogenesis with external distraction device]. AB - OBJECTIVE: To demonstrate a practical method for advancement of the midface using Le Fort I osteotomy and gradual distraction technique. METHODS: With the use of an external adjustable, rigid distraction device, we treated 6 patients with severe maxillary hypoplasia. Ages ranged from 11 to 15 years. They all underwent modified Le Fort I osteotomies assisted by gradual distraction. Four days postoperatively, distraction began at the rate of 1 mm/day for about 2 weeks. 4 weeks with the fixed distraction appliance and 6 weeks with a removable night time face-mask retention, we then analyzed all those preoperative and postoperative protocols. RESULTS: Predictable results were obtained. Midface advancement ranged from 8 to 13 mm. A satisfactory class I or II molar relationship is achieved. The aesthetic results are excellent. Up to now, no relapses have been observed. CONCLUSIONS: This method of modified Le Fort I midface advancement has been shown to be clinically practical and effective. PMID- 11780527 TI - [A study of fluoride-containing composite resins: fluoride release, water sorption and dissolution]. AB - OBJECTIVE: To study fluoride release and its impact on the basic properties. METHODS: Fluoride releasing was determined by F-electrodes, water sorption and dissolution of the materials were determined by weight/volume loss technique. RESULTS: The profile of fluoride release from fluoride-containing composites was different from that of compomer. Meanwhile, fluoride-containing materials showed larger values of water sorption (13.05-31.64 micrograms/mm3) and dissolution(5.88 24.80 micrograms/mm3) than controls. CONCLUSIONS: The F- releasing may affect physical and mechanical properties of fluoride-containing composites. PMID- 11780528 TI - [The correlation analysis between frequency of micronucleated cells of exfoliated oral mucosa cells and oral mucosa cells in different grading of oral leukoplakia lesions]. AB - OBJECTIVE: To provide evidence for using micronucleated cells of exfoliated oral mucosa cells in diagnosis and treatment of oral leukoplakias and chemopreventive studies of oral cancer. METHODS: Micronuclei of exfoliated oral mucosa cells and oral mucosa cells in 119 patients comprising 59 simple hyperplasia, 32 mild and moderate oral leukoplakia and 28 severe oral leukoplakia and oral squamous carcinoma by Feulgen stain method were examined, and micronuclei of exfoliated oral mucosa cells in 100 normal persons were also examined. RESULTS: Frequency of micronucleated cells of exfoliated oral mucosa cells in oral leukoplakia lesions was higher than that of normal persons. Frequency of micronucleated cells of exfoliated oral mucosa cells had a positive correlation with oral leukoplakia lesions(r = 0.9997, P < 0.001) and with frequency of micronucleated cells of oral mucosa cells (P < 0.001). CONCLUSIONS: Frequency of micronucleated cells of exfoliated oral mucosa cells are useful markers to the clinician to predict oral leukoplakia behaviour and prognosis and substitute for frequency of micronucleated cells of oral mucosa cells as intermediate endpoint in chemopreventive trials. PMID- 11780529 TI - [The application study of mimic operation with 3D-cut in maxillofacial bone tumor]. AB - OBJECTIVE: To study the feasibility of guiding operation planning and complication prevention. METHODS: Ten patients suffer from Maxillofacial bone tumour were examined with spiral CT. Firstly, to get three-dimensional reconstructive image of tumour and other tissues. Secondly, use 3D-cut software to cut off every layer of normal tissue and tumour mass. Lastly, to compare virtual operation with mimic operation in virtual operation process. RESULTS: Three-dimensional mimic operation clearly displays the relationship between tumor and surrounding tissues, reflect the actual operation condition. CONCLUSIONS: It is very useful designing operation program and predicting the potential complications before the actual operation. PMID- 11780530 TI - [The effect of non-surgical periodontal therapy on blood sugar level of non insulin dependent diabetes mellitus diabetics with periodontitis]. AB - OBJECTIVE: To investigate the effect of periodontal therapy on blood sugar level of non-insulin dependent diabetes mellitus(NIDDM) diabetics with periodontitis. METHODS: Patients with unfavorable control of diabetes were selected from out patients of the first affiliated hospital of Sun Yat-sen University of Medical Science. The percentage of bleeding on probing, probing depth and glycosylated hemoglobin level were studied at baseline, four weeks and eight weeks after non surgical treatment. RESULTS: The percentage of bleeding on probing and probing depth were significantly reduced in all the patients after treatment. The mean glycosylated hemoglobin level were significantly decreased in patients with advanced periodontitis while patients with moderate periodontitis showed no changes following therapy. CONCLUSIONS: The control of periodontal inflammation can improve metabolism to some extent in patients with diabetes mellitus, but the effect may relate to blood sugar level and periodontal conditions at baseline. PMID- 11780531 TI - [The application of auro-galvano-form ceramic crowns in clinic]. AB - OBJECTIVE: To evaluate the effects of auro-galvano-form ceramic crown in clinic. METHODS: The Ni-Cr alloy high-gold alloy and auro-galvano-form ceramic crowns were made respectively. Every kind was 200 pieces. 600 piece crowns were in total for 298 patients. The color of ceramic crowns was checked with Shade Eye. The color, fitness and fracture of ceramic crowns were checked in clinic. RESULTS: The results showed the aurogalvano-form ceramic crowns was similar to high-gold alloy ceramic crowns in color and fitness in clinic (P > 0.05). The effects of them were better than Ni-Cr alloy ceramic crowns in color and fitness significantly (P < 0.05). The fracture of 600 ceramic crowns was not found out in two years. CONCLUSIONS: The effects of auro-galvano-form ceramic crowns were perfect in color, fitness and fracture. It can be used in clinic. PMID- 11780532 TI - [An experimental study on physiotherapy for traumatic facial nerve injury]. AB - OBJECTIVE: To investigate the effects of electric stimulation, iontophoresis and electric stimulation with iontophoresis therapy in treating traumatic facial nerve injury. METHODS: Fifty rabbits were used. All right buccal branch of facial nerve were injured. The rabbits were randomly divided into five groups and treated by different stimulation pattern: (a) electric stimulation group; (b) iontophoresis group; (c) iontophoresis with electric stimulation group; (d) routine therapy group; (e) control group. The histologic morphology, quantitative indices of nerve fibers and electroneurography(ENoG) indices were analyzed. RESULTS: (a) Iontophoresis with Vitamin B1 and Vitamin B12 improved the regeneration of facial nerve myelin sheath. And had the best effect among these groups. (b) Electric stimulation had great effect on axon regeneration. (c) The group of electric stimulation with iontophoresis therapy had the best comprehensive effect on the nerve injury. CONCLUSIONS: Both electric stimulation and iontophoresis have good effects on nerve regeneration, when they are used in combination, the best comprehensive effect will be expected. PMID- 11780533 TI - [Value of Gallium-67 scanning in differentiation of malignant and benign tumor in oral and maxillofacial area]. AB - OBJECTIVE: To evaluate Gallium-67 scanning in differentiation of malignant and benign tumor in oral and maxillofacial region. METHODS: 41 patients with tumors in the oral and maxillofacial region were undergone Gallium-67 scanning. The results were correlated with the final pathologic diagnosis. RESULTS: Twenty out of 21 patients who had malignant tumors showed positive Gallium-67 scanning images (95.23%); three of 20 patients who had benign tumors also demonstrated positive results (15.00%). There was a significant difference between these two groups (P < 0.001). CONCLUSIONS: Gallium-67 scanning is a useful adjunct tool for differentiation of malignant and benign tumors in oral and maxillofacial region. PMID- 11780534 TI - [Serial cultivation of normal human oral keratinocytes]. AB - OBJECTIVE: To establish a method of culturing normal human oral keratinocytes. METHODS: Specimens obtained from healthy humans undergoing oral surgery were dissociated by Dispase and trypsin into a single cell suspension. The cells were grown in serum-free medium. Morphological characteristics were studied under light microscope and electron microscope (EM). Cytokeratins were showed by immunohistochemistry. RESULTS: The cells could be maintained in culture up to 4-5 passages, or 30-50 days. EM revealed that there were desmosomes and tonofibrils in the culture cells. The cells showed positive staining for cytokeratin antibody. CONCLUSIONS: The culture technique for growing normal human oral keratinocytes has been established. PMID- 11780535 TI - [Histologic study of the temporomandibular joints after ovariectomy in rats]. AB - OBJECTIVE: To investigate histologic changes of the temporomandibular joints (TMJ) after ovariectomy in adult rats. METHODS: Sixty-eight female SD rats aged twenty weeks were assigned to 2 groups. One group underwent bilateral ovariectomies served as experimental group. The other underwent sham ovariectomy served as control group. The rats were killed at the intervals of 1, 2, 4, 8 and 12 weeks postoperatively. Histologic observation of the TMJ was performed in a synchronous manner by using light microscopy(LM), scanning electron microscopy(SEM) and transmission electron microscopy (TEM). The serum levels of estrogen and bone mineral density of femur were also determined. RESULTS: In the experimental group, the serum levels of estrogen were obviously decreased, and bone mineral density of femur was significantly decreased at 12 weeks postoperatively. No obvious histological changes of TMJ of rats were observed at 1 and 2 weeks after the ovariectomy, whereas thickness of the condylar cartilage was increased, with irregular shape of chondrocytes at 4 and 8 weeks postoperatively. A serial of degenerative changes in the TMJ was observed in osteoporotic rats at 12 weeks after the ovariectomy. CONCLUSIONS: Estrogen deficiency in rats may cause alterations of the TMJ, and osteoporosis may predispose to degenerative changes in the TMJ. PMID- 11780537 TI - [To probe into the practicability of using the jaw position of eliminating TMJ clicks as the therapeutic position of repositioning splint]. AB - OBJECTIVE: To evaluate that it was practicable to use the jaw position of eliminating TMJ clicks as the therapeutic position of repositioning splint and to probe into the therapeutic mechanism of repositioning splint. METHODS: 25 patients with reducible disc displacement were treated with repositioning splint. The therapeutic jaw position was the position without TMJ clicking, then verified by Arthrography. The treatment effect was observed. RESULTS: Among 25 cases, 19 discs were completely recaptured, 5 incompletely recaptured, 1 not recaptured. Once the splints inserted, the movements of disc-condyle complex were smooth. After treatment finished, the opening types were improved, the clicks were lessened. CONCLUSIONS: It's practicable to use the jaw position of eliminating clicks as the treatment jaw position of repositioning splint. The therapeutic mechanism of repositioning splint may be that it altered the relationship of disc and condyle and improved their movement. That was favorable to fibrize the retrodiscal tissue and to strengthen the posterior band of disc. PMID- 11780536 TI - [The expression of TGF-beta receptors on cultured human dental papilla cells]. AB - OBJECTIVE: To observe the expression of TGF-beta receptors on cultured human dental papilla cells and the effects of TGF-beta on TGF-beta receptors of the cells. METHODS: The expression of TGF-beta receptors on cultured human dental papilla cells and the effects of TGF-beta on TGF-beta receptors of the cells were examined by cell culture and immunohistochemical technique and image analysis. RESULTS: Type I, type II receptors for TGF-beta in human dental papilla cells were stained strongly and type III was weakly positive. Image analysis indicated that all experimental groups had no obvious difference with control groups (P > 0.05). CONCLUSIONS: Cultured human dental papilla cells express TGF-beta type I, type II and type III receptors. TGF-beta has no obvious effects on the cell receptor expression. PMID- 11780538 TI - [The effect of immune bovine whey on cell-associated glucosyltransferase activity of Streptococcus mutans]. AB - OBJECTIVE: To study the effect of immune bovine whey on cell-associated glucosyltransferase (GTF) activity of S. mutans MT8148. METHODS: The immune milk was collected from cows immunized with cell-associated GTF overexpression strain B-29-33 of S. mutans MT8148. The control milk was from non-immunized cows. The immune absorbed whey was gotten from immune bovine whey which was absorbed with lyophilized Formalin-killed B-29 whole cells. Three kinds of whey were subdivided into three groups: 50 microliters, 70 microliters, 90 microliters. The content of insoluble glucan was estimated colorimetrically by anthrone method. RESULTS: The control bovine whey had an enhancing GTF activity (407.00%-485.62%). The immune absorbed whey inhibited partly the enhancing GTF activity (208.74%-273.00%). The immune whey inhibited significantly the GTF activity (70.24%-38.62%) and the inhibition showed a tendency to depend on doses. CONCLUSIONS: The immune bovine whey inhibits significantly the cell-associated GTF activity of S. mutans MT8148. PMID- 11780539 TI - [The effects of local stress on bone mass of mandibles in ovariectomized rats]. AB - OBJECTIVE: To observe the relationship between the change of stress environment of mandibles and their bone mass in normal and ovariectomized(OVX) rats. METHODS: The high and low stress environment models of mandibles were established by unilateral maxillary molars extraction. The masticatory sides of the mandibles were regarded as the high stress sides and the non-masticatory sides were regarded as the low stress sides. Ovariectomized rats were utilized as postmenopausal osteoporosis models and Sham-ovariectomized(Sham-OVX) rats as control group. According to these ideas, 48 female rats were divided into 4 groups: 1) OVX + extraction group; 2) OVX + non-extraction group; 3) Sham-OVX + extraction group; 4) Sham-OVX + non-extraction group. The bone mineral densities (BMD) of all mandibles were measured by single-photon absorptiometry bilaterally 1.5 months and 3 months after extraction. RESULTS: The mandibles of ovariectomized rats had lower BMD than those of normal rats(P < 0.05). To normal rats, the BMD of mandibles in low stress sides were lower than the high stress sides 3 months after extraction(P < 0.05), but the BMD of the two sides were not significantly different to those of the non-extraction control ones(P > 0.05). To ovariectomized rats, the BMD of mandibles low stress sides were much lower than the high stress sides(P < 0.01). The BMD of mandibles in low stress sides were much lower than non-extraction ones of OVX group after 3 months(P < 0.05). The BMD of the high stress sides were much higher than those of the non-extraction control ones of OVX group(P < 0.05), but they were still lower than those of the non-extraction control ones of Sham-OVX group(P < 0.05). CONCLUSION: The results indicate that the masticatory functions(the high stress environment) tend to conserve the mandibular bone mass in patients with systemic osteopenia such as postmenopausal osteoporosis and the masticatory deficiency (the low stress environment) tends to aggravate mandibular bone loss induced by systemic osteopenia. The masticatory functions should be rehabilitated for these patients as early as possible. PMID- 11780540 TI - [Influence of multiple coats of bonding agent on the bond strength of amalgam bonding]. AB - OBJECTIVE: To evaluate the effect of multiple coats of bond on the bond strength of amalgam bonding. METHODS: One or two layers of Scotch-bond multi-purpose plus dental adhesive agent were applied on the dental walls of two groups of teeth respectively prior to amalgam condensation. The third group was set for control which only had amalgam filling. After one week, thermocycling, shear bond strength were tested for all specimens with 1195-Instron testing machine. Data were analyzed by SPSS 8.0. The SEM observation were made in other five modals with one or two layers bonding. RESULTS: The shear strengths of two or one layer bond and control one were 25.77, 20.69 and 13.05 MPa separately. The difference among them was statistical significant (P < 0.01). CONCLUSIONS: The microlocking was more obvious in specimens of two bonding layers. PMID- 11780541 TI - [An analysis on need and demand for dental service in urban residents of Beijing]. AB - OBJECTIVE: To analyze the needs and demands for dental services in urban residents of Beijing, and to forecast developmental trends of dental demand in the future. METHODS: There were 1,517 subjects examined by a stratified, clustering, random sampling, and a questionnaire survey were completed. RESULTS: The prevalence of oral diseases was 97.6%, but only 31.5% of subjects visited the dentist in a year, the total number of residents who had need of dental care were 4,412,010 more than that of demand level. Potential demand was mainly due to the negative awareness of people and problem from service provider. It was predicted that, if the potential demand caused by awareness and service provider were satisfied, the demand for dental care would increase by 69.4% and 13.2%, respectively. By the year of 2005, the demand will increase by 1.14%, and the value will be 3.76% in 2010. CONCLUSIONS: A substantial discrepancy is found between oral disease presence and demand for dental service. The levels of demand are also irrational. The large potential demand is caused by both receiver and provider's factors. At last, the future demand for dental care is forecasted under three hypothesis. PMID- 11780542 TI - Critical appraisal personal learning projects. PMID- 11780543 TI - Preparing and presenting a scientific paper. PMID- 11780544 TI - Computed tomography of obturator hernias: case report. PMID- 11780545 TI - Comparison of image quality indicators among mammography facilities in Ontario. AB - OBJECTIVE: To compare the technical aspects of image quality of mammography machines in facilities across Ontario. METHODS: Eight mammographic physics consultants took measurements and calculated accreditation phantom scores, mean glandular dose, entrance exposure, average optical density, half value layer and the limiting resolution of the imaging chain for 100 mammography machines across Ontario. RESULTS: Of the 100 machines, 39 were affiliated with the Ontario Breast Screening Program (OBSP), and the remaining 61 were applying to become OBSP affiliates. All of the OBSP facilities and 32 of the applicants were accredited with the Mammography Accreditation Program (MAP) of the Canadian Association of Radiologists (CAR). All OBSP facilities had passing phantom scores, and 84% of the applicants with CAR accreditation and 79% of those without had passing phantom scores. The mean glandular dose was 1.5 (range 1.0-1.9, standard deviation [SD] 0.22) mGy for OBSP facilities, 1.3 (0.8-1.8, SD 0.29) mGy for CAR accredited and 1.4 (0.9-1.9, SD 0.24) mGy for nonaccredited applicants. Mean entrance exposures were 798 (540-1280, SD 135) mR, 717 (430-980, SD 153) mR and 770 (520-930, SD 116) mR for the OBSP, accredited and nonaccredited facilities respectively. There were no appreciable differences in the mean optical densities (approx. 1.62 OD), mean half-value layers (approx. 0.34 mm Al) or mean resolutions measured with the large focal spot (nominal size of 0.3 mm) either parallel (approx. 16 line pairs/mm) or perpendicular (approx. 14 line pairs/mm) to the cathode-anode axis of the x-ray tube, among the 3 types of facilities. CONCLUSION: Image quality is increased and variability is decreased in facilities participating in a province-wide screening program. PMID- 11780546 TI - Continuous quality improvement process to track lost radiographs and reduce losses. AB - OBJECTIVE: To describe a quality improvement process that was initiated in a Department of Radiology to reduce the number of incomplete or "lost" imaging studies and decrease the time from the initiation of an imaging study to printing of the final report. METHODS: Incomplete cases were defined as those imaging studies that did not have a signed final report more than 3 days and less than 90 days after imaging. A computer program was written to generate a monthly incomplete case list from the radiology information system database; each step in the process, from patient arrival to final report printing, was analyzed and a list of root causes (for the incomplete cases) was developed. Short- and long term interventions were introduced and the effects were monitored from 1992-1999. RESULTS: Problems were identified at each step in the process. Although some of the root causes originated outside the authority of the Department of Radiology, interventions we implemented within the department reduced the incomplete list by 72%, from a high of 2.8% of all imaging examinations to less than 0.8%. Continual monitoring of the problem is necessary to maintain this level. CONCLUSION: The number of incomplete or "lost" imaging studies can be decreased using a continuous quality improvement process. This leads to improved patient care and increased revenue. PMID- 11780547 TI - Radiologic placement of central venous catheters: rates of success and immediate complications in 3412 cases. AB - OBJECTIVE: To determine the success and immediate complication rates associated with 3412 central venous catheter placements performed in an interventional radiology suite. METHODS: Success and immediate complication rates were prospectively recorded for 3412 consecutive patients who had central venous catheters radiologically placed at a tertiary care centre between July 1993 and October 2000. The indication for placement and the insertion site were also recorded. RESULTS: The most common indication for both short- and long-term venous access was hemodialysis, and the right internal jugular vein was the most common site for catheter insertion. Placement was successful for 98.8% of tunnelled lines and 99.3% of temporary catheters. The rate for immediate complications (including pneumothorax, air emboli, bleeding and arterial puncture) for tunnelled catheter placements was 3.8% and for temporary catheter placements was 1.6%; no major complications were documented. CONCLUSION: Our results lend further evidence to the claim that the success and immediate complication rates of radiologically placed central venous catheters compare favourably with blind placement and surgical placement of central venous catheters. PMID- 11780548 TI - Computed tomography to assess pulmonary injury associated with concurrent chemo radiotherapy for inoperable non-small cell lung cancer. AB - OBJECTIVE: To characterize serial computed tomography (CT) findings of pulmonary injury after a uniform regimen of concurrent chemo-radiotherapy in inoperable non small cell lung cancer, and to compare the radiation-induced lung toxicity with other concurrent chemo-radiation regimens. METHODS: Twenty-four patients with advanced non-small cell lung cancer received 2 induction cycles of cisplatin and vinblastine, followed by 2 further cycles of cisplatin and vinblastine, concurrent with 60 Gy radiation at 2 Gy per fraction. Radiation-induced lung injury in the acute and chronic phases was assessed by serial CT scans and compared with preradiation baseline scans. Acute radiation pneumonitis was evaluated using the Common Toxicity Criteria, and chronic radiation fibrosis was graded according to the European Organisation for Research and Treatment of Cancer--Radiation Therapy Oncology Group Scale. RESULTS: Seventeen (81%) patients had characteristic CT findings of radiation-induced pulmonary damage, which were confined to the radiation ports. Although patchy nonhomogeneous and air-space opacities characterized acute radiation pneumonitis, and homogeneous opacities with loss of volume were typical for chronic fibrosis, ground-glass opacities were found frequently in both phases. Acute radiation pneumonitis grade 1 was seen in 29% and grade 2 in 9.5%. Chronic radiation fibrosis grades 1, 2 and 3 were found in 14%, 33% and 19% of the patients respectively. Median survival time was 13 months. CONCLUSION: CT enables detailed evaluation of radiation-induced pulmonary injury after concurrent chemo-radiation for inoperable non-small cell lung cancer. Although survival time with the present regimen is comparable to other concurrent chemo-radiation regimens, a high incidence of radiation injury was found, though the severity was not life threatening. PMID- 11780549 TI - Role of chest radiography after the insertion of a subclavian vein catheter for ambulatory chemotherapy. AB - OBJECTIVE: To determine the need for routine chest radiography after the insertion of a catheter via the subclavian vein for ambulatory chemotherapy. METHODS: The case notes of all patients who had undergone catheter insertion between 1994 and 1998 were reviewed retrospectively. RESULTS: Of 3844 cases, there were 52 (1.4%) complications detected on chest radiographs after catheter insertion, 46 of which were pneumothoraces; 15 of the 46 patients had a clinical risk factor at insertion (technical difficulty or symptoms), and 14 had a risk factor after insertion (respiratory symptoms and signs). For 22 (47.8%) pneumothoraces, there was no clinical risk factor identified; 3 of these patients required intercostal drain insertion. Other complications (n = 6) included catheter malposition and kinking, and chest radiography made an important contribution to management in at least 1 of these cases. CONCLUSION: In approximately 0.1% of cases of catheter insertion in the subclavian vein, chest radiography detected a clinically occult complication significant enough to require intervention. PMID- 11780550 TI - Staphylococcus aureus septic pulmonary emboli presenting as angioinvasive aspergillosis: case report. PMID- 11780551 TI - Technetium Tc 99m DTPA galactosyl human serum albumin to measure changes in hepatic functional reserve after transcatheter arterial embolization of the liver. AB - OBJECTIVE: To describe the acute and subacute changes in hepatic functional reserve using technetium Tc 99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m DTPA GSA) in patients with hepatocellular carcinoma and liver cirrhosis who had undergone transcatheter arterial embolization (TAE). METHODS: Sequential Tc-99m DTPA GSA hepatic scintigraphies were performed prospectively in 26 consecutive patients with hepatocellular carcinoma and liver cirrhosis approximately 1 week before, 2 days after and 1 month after TAE. Counts per 10 seconds of the heart region of interest on 3- and 15-min images and the liver region of interest on a 15-min image were calculated. RESULTS: Clearance index decreased (p < 0.001) and receptor index and modified receptor index increased 2 days after TAE (p < 0.001 and p = 0.004, respectively), but these changes did not persist 1 month later. CONCLUSION: This study has established an expected pattern of behaviour of the liver after TAE, which could be used to monitor progress of patients who undergo the procedure. PMID- 11780552 TI - Bone marrow failure and hematological abnormalities in alcoholic liver cirrhosis. AB - Long term alcohol abuse may result in bone marrow damage and hematologic abnormalities. In the study we evaluated bone marrow and peripheral blood changes in patients with alcoholic cirrhosis. Although majority of the patients (91%) presented with hematologic abnormalities such as leukopenia, thrombocytopenia, low hemoglobin level, only mild alterations in bone marrow were observed. The hematopoietic tissue was of high cellularity with features of activation and moderate myelofibrosis. PMID- 11780553 TI - Autoantibodies in chronic liver diseases. AB - 177 patients with chronic liver disease, among 115 with chronic hepatitis and 61 with liver cirrhosis were subjected to the autoantibodies examinations (ANA, AMA, ASMA, APCA, LKM, ATA) by means of immunofluorescent method (IFA). 25% of cases showed autoantibodies of autoimmunological disease index titre (1:80). Autoantibodies occurred more frequently in woman (75%), mainly in the age of 40 60. Patients with hepatic cirrhosis revealed autoantibodies as frequently as other patients. Among patients infected with hepatotropic viruses (HBV, HCV) with chronic liver diseases, autoantibodies were present in 23-28% of cases and in patients with chronic liver diseases of non-infectious etiology, autoantibodies were observed in 25% of cases. PMID- 11780554 TI - TNFRs and IL-6R transmembrane receptors expression and release of their soluble forms by neutrophils and mononuclear cells from cancer patients. AB - TNF-alpha and IL-6 are multipotential mediators involved in the control of many host's reactions to tumour. Their biological effects are mediated through the membrane-bound receptors (TNFRp55, TNFRp75 and IL-16R respectively) which can exist in soluble forms. In the present study we compared release of soluble sTNFRp55, sTNFRp75 and sIL-6R with expression of their membrane-bound on PMN and PBMC. Cells were isolated from patients with cancer diseases with a different location and histological classification. We have found that alterations of membrane-bound TNFRp75 expression and in the secretion of soluble TNFRp75 form, as opposed to other receptors examined, are characteristic features of neutrophils and mononuclear cells isolated from cancer patients. The similar changes observed in the expression of TNFRp75 by PMN and PBMC appear to confirm a significant role of PMN in the tumour response mediated by TNF-alpha. Furthermore, the altered membrane-bound TNFRp75 expression and sTNFRp75 secretion appear to depend on the tumour type. PMID- 11780555 TI - Does parasitic infection affect platelet factor 4 concentration? AB - Blood platelets actively participate in defense mechanisms of the organism, e.g. in antiparasitic immunity. Platelet stimulation may be a result of direct contact with parasite, increased IgG and/or IgE concentrations, the presence of complement, CRP or lymphokins. The aim of the study was to find out whether parasitic infection induces platelet activation. The study involved 35 patients (30 patients were infected with Giardia intestinalis and 5 patients were infected with Echinococcus granulosus). Blood for analysis was collected twice, before treatment (A1) and after it (A2). The concentrations of platelet factor 4 were assayed using a set of ASSERACHROM according to the immunoenzymatic method with labelled antibodies. The mean concentration of platelet factor 4 (PF4) was 20.3 +/- 9.4 IU/ml in the patients prior to the antiparasitic therapy and being reduced to 6.0 +/- 3.0 IU/ml after treatment. In the control group the mean PF4 concentration was 2.27 +/- 0.08 IU/ml. The differences between the values in control group and the two groups tested were statistically significant. Although platelets do not get into a direct contact with the parasite, an increase is observed in the concentration of platelet factor 4, which may indicate the involvement of platelets in the parasitic disease. PMID- 11780556 TI - Ethanol and N-acetylcysteine influence on the development of liver changes in experimental methanol intoxication. AB - The evaluation of ethanol and N-Acetylcysteine (NAC) influence on histopathological changes in rat liver intoxicated with 3 g of methanol/kg b.w. was conducted, based on morphological examinations in light and electron microscope. The rats received intragastrically 3.0 g of methanol/kg b.w. as a 50% solution, 10% ethanol for 24 hours before methanol and next 48 hours after methanol ingestion and NAC (150 mg/kg b.w.) after 15 min. methanol administrated. The results indicate that methanol intoxication causes pronounced morphological changes in the examined organ. Ethanol administered to methanol-intoxicated rats caused intensification of certain parameters of hepatocytes morphological damage. A simultaneous administration of methanol and NAC resulted in a lower degree of parenchymal damage. PMID- 11780557 TI - beta-Thromboglobulin in patients with acute myocardial infarction according to the treatment. AB - Many studies report on the increased activity of platelets in patients with heart disease, especially with acute myocardial infarction (MI). The aim of the present study was to evaluate dynamics of beta-thromboglobulin (beta-TG) concentration in patients with MI according to the disease duration and type of treatment. We investigated 29 patients, who were divided into two groups according to the type of treatment. beta-TG concentration was determined using the immunoenzymatic method (ELISA). Blood was taken 1st, 3rd, 5th, 8th and 11th day of infarction. Our results indicate that in the course of myocardial infarction there is a change in platelet activation. The treatment applied affects beta-TG concentration, and the thrombolytic therapy inhibits platelet activation. PMID- 11780558 TI - The superficial skin temperature of low extremities in patients with sciatica. AB - In some patients with lumbar disc herniation pain of various character and intensity is observed. Besides the pain a number of patients present burning or cold sensations. The superficial temperature of the lower extremities was evaluated in 39 patients with ischialgia, classified for surgical treatment. The differences of skin temperature, however not statistically significant, between the affected and non-affected limbs were found. PMID- 11780559 TI - Malignant and benign tumours of liver--problems of diagnostics, treatment and complications. AB - Non-invasive diagnostics development, and particularly introduction of ultrasound to everyday medical practice contributed to early detection of tumour lesions in the liver. The aim of the research was to analyse the patients with tumour lesions of livers in the north-eastern region of Poland. 325 patients with tumour lesions in livers underwent surgical treatment between year 1978 and 2000. In 197 patients metastatic malignant tumours were found in livers, while in 24 cases- primary malignant neoplasms of the organ. In the remaining cases benign tumours, mostly non-parasitic cysts were found. Out of 325 patients, who were surgically treated, 80 underwent resection procedures of liver parenchyma with tumour, 17- enucleation of tumour lesion with the enclosing capsula, 14--abscess drainage with necrotic mass evacuation. In 11 cases of non-parasitic as well as parasitic cysts fenestration was performed due to high risk of surgery, while in the remaining patients laparotomy was only performed and segments for histopathologic examination were taken due to the progression of the neoplasmatic disease. In the patients who had undergone resections of liver parenchyma in the postoperative course we noted complications such as: prolonged cholerrhagia from peritoneal cavity, stress duodenal ulcers complicated by bleeding, bleeding from liver parenchyma at the section line, jaundice as well as cisterns of fluid at the parenchyma section line. Mortality in the patients after the resection procedures of liver in our material was 7.5%. The development of diagnostics contributed to early detection and surgical treatment of tumour lesions of liver. The observation of our patients showed that resection procedures in benign tumours lead to complete recovery, while in malignant lesions--to clearly prolonged survival. PMID- 11780560 TI - gamma delta-Lymphocytes in the peripheral blood of patients with rheumatoid arthritis--correlation with clinical and laboratory parameters of the disease and with the treatment used. AB - Rheumatoid arthritis (RA) is a chronic, autoimmune disease in the pathogenesis of which T-lymphocytes are believed to play a crucial role. The aim of this work was to investigate a subpopulation of gamma delta-lymphocytes in the peripheral blood of patients with RA in the context of chosen parameters of the disease. Moreover, we studied the influence of disease modifying antirheumatic drugs (DMARDs) on the number of gamma delta-lymphocytes in the peripheral blood of patients with RA. The gamma delta-lymphocytes were studied using monoclonal anti-delta 1 antibodies labelled with fluorescein (Becton Dickinson) then counted under a fluorescence microscope (Olympus). We found a significant increase in the number of gamma delta-lymphocytes in the peripheral blood of patients with RA as compared with normal controls. The highest numbers were observed in patients with RA and extraarticular manifestation of the disease. Treatment with DMARDs led to a gradual normalisation of the elevated values of gamma delta-lymphocytes. PMID- 11780561 TI - Three-dimensional sonography in the diagnosis of hepatic hemangiomas. AB - The purpose of the study was to compare power 3-D with conventional 2-D sonography with color and power Doppler in assessment of tumor vascularity in small hepatic hemangiomas. The study group comprised 12 patients (7 males and 5 females) aged 28-60, (mean 44) with diagnosed hemangiomas. In all the patients 2 D and 3-D sonography was performed and their results were compared. Both color and power Doppler 2-D sonography failed to detect blood flow in the tumors. Blood flow signals were detected in 3-D power Doppler sonography. 3-D power Doppler is superior to 2-D color and power Doppler imaging in the detection of blood flow signal in hemangiomas. PMID- 11780562 TI - Surgical management of chronic pancreatitis. AB - During the past 21 years 222 patients with chronic pancreatitis have undergone surgery at the Department of General Surgery, Medical School Bialystok. In 117 cases (52.7%) resection was performed and 48 patients (21.6%) had anastomotic procedures and the rest of patients underwent bile duct anastomotic surgery or were re-operated on because of surgical complications. Based on the own clinical experience and the latest data from the world literature diagnostic criteria and indications for surgical treatment of chronic pancreatitis are shown below. Good results obtained in 192 cases (86%) strongly support our opinion that resection procedures in chronic pancreatitis are the most effective management however patients should be operated on in specialized centers with good diagnostic bases because a correct diagnosis is essential while choosing the appropriate line of treatment. PMID- 11780563 TI - Evaluation of polypeptide growth factors in the process of dental implant osseointegration. AB - The aim of the present study was to evaluate the concentration of three polypeptide growth factors: transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) in the blood of patients treated with Italian Logos system implants. The blood for analysis was collected three times: prior to the surgery, the day after and four months after the procedure before implant exposure for the prosthetic phase. The concentration of growth factors was assayed using ELISA method with R&D kits. The mean serum PDGF concentration on the first day and after 4 months following the procedure were comparable to the preliminary examination. The mean serum concentration of TGF beta in the second examination increased significantly compared to that before surgery. Four months later its mean concentration was lower than in the second examination, but still higher than in the preliminary examination. The mean serum FGF concentration in our patients remained similar throughout the study. Based on presented above data we conclude that inflammation process caused by tissue injure during implantation stimulates TGF beta release what can be detected by increase of it's concentration in blood serum. PMID- 11780564 TI - Clinical and radiographic evaluation of periodontal therapy using enamel matrix derivative (Emdogain). AB - The aim of the present study was to evaluate clinical and radiographic outcome following the application of enamel matrix derivative--Emdogain in the treatment of the bone defects due to periodontitis. The study included 25 generally healthy patients with advanced periodontitis. Clinical and radiographic examination was carried out twice: before the procedure and a year after treatment. The following clinical parameters were evaluated: probing pocket depth (PPD), clinical attachment level (CAL) and gingival recession (GR). Defect depth, width and bone defect fill were assessed on the radiographs. A year after surgery the follow-up examination found a significant improvement of clinical parameters. The mean depth of gingival pockets was reduced from 8.76 +/- 1.74 mm to 4.52 +/- 1.56 mm. The mean CAL value was also decreased from 10.72 +/- 1.56 mm to 7.82 +/- 1.68 mm. Analysis of radiographs showed a statistically significant reduction in depth and width of bone defects. Our results indicate a good clinical and radiographic effect following the application of Emdogain in the treatment of periodontal intrabony defects. PMID- 11780565 TI - Kallikrein-kinin system activation and its interactions with other plasma haemostatic components in the coronary artery disease. AB - Concentrations of kininogens, prekallikrein, fibrinogen and antigens of protease inhibitors as well as kininase, fibrinolytic and antipapain activities were estimated in blood plasma (or serum) of patients with coronary artery disease (CAD) before and after the exercise test. The study was conducted on 44 subjects with chronic, stable CAD and 54 myocardial infarction patients (15 treated with streptokinase and 39 subjected to primary percutaneous transluminal coronary angioplasty, PTCA). The patients were divided into two subgroups: treated and untreated with angiotensin I-converting enzyme inhibitor (ACE-I), enalapril. Activation of the fibrinolytic system and the prekallikrein during the exercise test was demonstrated. No significant kininogen consumption was observed. A decrease in kininase activity was found. The results suggest the possibilities of endothelial cells contribution to plasminogen activation in CAD patients. Kininogen and kallikrein directly, or through the released kinins, may participate in regulation of endothelial cell hemostatic functions. Conversion of plasminogen to plasmin may undergo under the influence of kallikrein. The bradykinin induces the tissue plasminogen activator (t-PA) secretion, which depends also on the increased blood flow during the exercise test. PMID- 11780566 TI - Variability of electrophoretical mobility of nuclei in human ontogenesis. AB - Estimation of human biological age is one of the most difficult objectives within the auksological sciences. The methods applied so far are not sufficient enough. Assessment of the electrophoretic mobility of cellular nuclei index (EMN index) offers new possibilities. The aim of the work was to examine the behaviour of EMN in various phases of human ontogenetic development. The study revealed that each of the age groups in consecutive phases of ontogenetic development presented specific values in EMN. PMID- 11780567 TI - Peripheral blood T, B lymphocytes and NK cells in primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) is an autoimmune disease with progressive destruction of the bile ducts and cholestasis. The most of epithelial cells in the bile ducts has molecule MHC I and II class expression which induced intensive immunological reaction and produced antimitochondrial autoantibodies (AMA). It leads to the destruction of own cells in PBC. The main part in the development of the disease have T cells, B cells, and NK cells. We analyzed subpopulation of lymphocytes in peripheral blood in 16 patients with PBC by flow cytometry. We noted statistically significant increase of NK CD16+ + CD56+ cell value and activated T CD3+ + HLA DR+ cell value in peripheral blood in PBC. Slightly increase in the value of CD4+ cells and slightly decreased CD8+ cell value were observed. However, the CD4/CD8 ratio was elevated statistically and it was 2.3 (healthy subjects--1.7). Lymphocyte T and B subpopulations remained normal. The results showed that the main role in PBC is played by NK cells and activated T cells. PMID- 11780568 TI - The influence of green tea on the activity of proteases and their inhibitors in plasma of rats after ethanol treatment. AB - Ethanol oxidation in the liver is accompanied by formation of acetaldehyde and free radicals. These compounds can react with biologically active proteins, including proteolytic enzymes and their inhibitors. The aim of this paper was to determine the influence of green tea on the activity of cathepsin G and elastase and their inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin, total antioxidant status and lipid peroxidation in plasma of young rats chronically intoxication with ethanol. The activity of cathepsin G and elastase was increased, while the activity of their inhibitors was reduced after ethanol treatment. AT the same time, the total antioxidant status was significantly decreased while lipid peroxidation measured as malondialdehyde and 4 hydroxynonenal was significantly increased. Giving green tea to rats did not change the proteases and their inhibitors activity, but significantly increased total antioxidant status and decreased lipid peroxidation. Drinking green tea with ethanol partially prevents the changes observed after ethanol intoxication. PMID- 11780569 TI - The concentration of C-terminal propeptide of type I procollagen in blood serum in the course of mandibular fracture healing (preliminary report). AB - One of the basic measures of quality of repairing processes of soft tissue and bone injury is collagen synthesis. C-terminal propeptide of type I procollagen (PICP) is admitted index of type I collagen biosynthesis. The aim of the study was estimation of PICP concentrations in the course of fracture repair process in relation to the treatment method. The material of investigations was blood serum of 25 men (age 20-30 years) with fracture of mandible. The patients were divided into 2 groups depending on the method of treatment: I group was patients treated non-surgical method (n = 12); II group--surgical method (n = 13). Blood samples in the first group were taken on 2nd, 14th, 42nd, 90th day of healing process and additionally on 2nd and 14th day after surgery--in the second group. The PICP concentrations in blood serum were determined by RIA method. Statistical analysis of results shown significant increase of PICP concentrations in I group of patients in 14th (167.1 +/- 42.8 micrograms/L) and in 42nd (216.0 +/- 59.1 micrograms/L) day of healing process in comparison to the values in the second day after injury--the first study (124.3 +/- 41.8 micrograms/L). In the II group of patients the statistically significant increase of PICP concentration in 14th day after surgical procedure (156.9 +/- 30.5 micrograms/L), 42nd (163.1 +/- 35.3 micrograms/L) and in 90th (153.1 +/- 40.2 micrograms/L) day of healing process after injury in comparison to the values in the second day after injury--the first study (119.9 +/- 35.8 micrograms/L). The results indicate, that a normal course of mandibular fracture healing influences the change in PICP concentrations in serum in examined men. A different dynamics of PICP concentrations, observed in the serum in patients with mandibular fractures treated surgically and non-surgically, suggests various mechanisms of bone tissue reconstruction connected with the method of treatment. PMID- 11780570 TI - Lichens of the Knyszynska Forest (NE Poland). AB - During the period 1991-1999 the lichen species composition of 26 reserves of the Knyszynska Forest were examined. 315 taxa, including 271 species were found. Epiphytic lichens were predominant, while epilithic species were the least common. Of the coniferous trees, pine (Pinus sylvestis) was the habitat which supported most species (67), and common larch (Larix decidua) the fewest (5). Only two species were found on juniper (Juniper communis). Of deciduous trees, the largest number of species developed on oak bark (Quercus robur) (102), the fewest on elm bark (Ulmus laevis) (2). In the case of deciduous bushes most lichen taxa were noted on hazel (Corylus avellana) (21) and only one on hawthorn (Crataegus monogyna). The commonest species were Hypogymnia physodes and Lecanora conizaeoides, which were encountered in all 26 reserves. PMID- 11780571 TI - Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL 8) in patients treated with dental implants. AB - The aim of the present study was to evaluate the levels of proinflammatory interleukins (IL)--IL-1, IL-6 and IL-8 in the blood of patients subjected to dental implant anchorage procedures. The study involved 10 generally healthy people aged 27-52, 4 men and 6 women. The patients were characterised by normal oral hygiene and lack of clinical symptoms of oral inflammation. Surgical procedures used Italian Logos system dental implants. The blood for analysis was collected three times: prior to surgery, one day and four months after the procedure before implant exposure. Interleukin levels were assayed with the ELISA method. The results were subjected to statistical analysis using Wicoxon's test. In all the cases examined soft tissue healing following the procedure was uneventful. The three consecutive examinations revealed similar IL-1 blood levels. Mean serum concentrations of IL-6 and IL-8 increased significantly in the second examination and returned to the close-to-initial values after 4 months. Increase of blood serum levels of IL-6 and IL-8 in the first day after implantation reflects local inflammation process caused by tissue impair. PMID- 11780572 TI - Insulin-like growth factor-I (IGF-I) in serum and bone tissue during rat mandible fracture healing. AB - Insulin-like growth factor-I (IGF-I) is potent stimulator of proliferation and differentiation of osteoblasts, the biosynthesis of collagen type-I and noncollagenous proteins and alkaline phosphatase activity. The role of IGF-I in bone repair has not as yet been clearly defined. The aim of the present study was the quantitative analysis of IGF-I in the serum and tissue in four phases of fractured jaws healing in rat models. IGF-I concentrations in the serum and bone extracts were determined by RIA. In respect to the control group (K) the significant increase of IGF-I occurred in the serum in phase I (211 +/- 68 ng/ml, K-153 +/- 50 ng/ml) (p < 0.05). At the tissue levels a statistically significant increase in IGF-I was confirmed in phase II (262 +/- 60 ng/g, K-182 +/- 56 ng/g) (p < 0.05). The present results demonstrate that in rat models with fractured jaws in the first two phases of healing elevated levels of IGF-I in the serum and bone tissue were observed which indicate the significant role of this polypeptide in the early healing stages. PMID- 11780573 TI - Histochemical and ultrastructural study of the effect of natrium fluoride on glycogen content in rat hepatocytes. AB - The aim of the study was to evaluate the effect of natrium fluoride (NaF) on glycogen content in hepatocytes of the offspring rats receiving fluoridated water, basing on histochemical (PAS reaction) and ultrastructural examinations. The experiment used 90 rats obtained from 30 mothers. The animals were given fluoridated water in two different concentrations: 10.6 mg NaF/l and 32.0 mg NaF/l. Material for analysis consisted of liver specimens collected on day 4, 14, 30, 60, 90 and 120 of rats' life. The rats were exposed to fluoride from the intrauterine life, during lactation, till full maturity. The experiment revealed the effect of super-optimal concentrations of natrium fluoride on carbohydrate metabolism of the rat. PMID- 11780574 TI - Adenosine deaminase activity in the gastric mucosa of duodenal ulcer patients in relation to the severity of chronic gastritis and gastric acid secretion. AB - Earlier reports suggested that adenosine deaminase activity in the gastric corpus mucosa depends upon either gastric acid secretion or severity of chronic gastritis. Knowing that gastric acid secretion corresponds well with histological status of the gastric mucosa, the aim of this study was to determine the enzyme activity in relation to these two factors evaluated simultaneously. The study was conducted on Helicobacter pylori positive duodenal ulcer patients treated for two weeks with either omeprazole alone or omeprazole in combination with amoxycillin and tinidazole. It was found that these two therapeutic regimens decreased adenosine deaminase activity only in the gastric corpus mucosa and a decline was more deeper in patients on omeprazole monotherapy. Moreover, omeprazole monotherapy inhibited completely basal gastric acid secretion and did not change the severity of chronic gastritis, while omeprazole-based eradication therapy decreased both the gastric acid secretion and severity of chronic gastritis. One month after completion of eradication therapy adenosine deaminase activity returned to the pretreatment values but severity of chronic gastritis decreased further. The results of the present study indicate that adenosine deaminase activity in the gastric corpus mucosa depends primarily upon gastric acid secretion but not upon the severity of Helicobacter pylori associated chronic gastritis. PMID- 11780575 TI - Aerosol hamycin is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. AB - Invasive pulmonary aspergillosis is a major life threatening complication among transplant recipient and patients receiving cancer chemotherapy. In a rat model of progressive pulmonary aspergillosis that is characterized by hyphal bronchopneumonia, aerosol hamycin (aero-H; 0.68 mg/kg given 2 days before infection) significantly delayed mortality in rats compared with animals in control group. The first death in the aero-H-treated group occurred on day 12, by which time six of the eight control animals had died. The same dose of aero-H given as treatment (0.68 mg/kg given 24 h after infection and than daily for 6 days) was also effective. In this trial, eight of the ten animals treated with aero-H survived for 7 day, whereas only one of ten control animals survived. Colony counts in lungs homogenates obtained 24 h after infection showed an 80 fold reduction in the number of viable spores in animals that had received 2.8 mg/kg doses of aero-H 2 days prior to infection. At 48 h after administrating a single 0.68 or 1.36 mg/kg dose of aero-H, mean lung concentrations were 1.25 and 2.60 mg/g tissue, respectively. From the results of the present study it was concluded that aero-H killed inhaled spores and delays the progression of pulmonary aspergillosis by inhibiting mycelial proliferation. PMID- 11780576 TI - Hamycin therapy of murine disseminated candidiasis: efficacy and interaction with fluconazole. AB - The efficacy of antifungal agent, hamycin, in a murine model of disseminated candidiasis was studied. Mice were intravenously infected with Candida albicans blastoconidia and treated for 14 days with intraperitoneal hamycin, oral fluconazole, or a combination of these two. Hamycin alone was most efficacious in prolonging survival and in decreasing renal colony counts, usually with complete sterilization of the kidneys by the end of the treatment period. Fluconazole improved survival rates and effected a decrease in renal colony counts, but kidneys were not microbiologically sterilized. Combination therapy with hamycin and fluconazole did not result in a decrease in the efficacy of hamycin by either end point (survival or renal colony counts). High-pressure liquid chromatographic analysis of Hamycin concentrations in serum indicated lowlevels of absorption of the drug. From the results of the present study, it can be concluded that hamycin is effective in the treatment of murine invasive candidiasis and that the theoretical concern about adverse interactions between the two drug does not apply to the dosages studied in these experiments. PMID- 11780577 TI - Cathepsin D activity in colorectal cancer. AB - Cathepsin D is one of the main proteolytic enzymes involved in the neoplastic process. The aim of the study was to evaluate the activity of cathepsin D in 36 colorectal adenocarcinomas (of the colon and rectum) at stage pT3 of clinical advancement and histological grade G2. The correlation of cathepsin D activity with the stage of anatomo-clinical advancement and the presence of chosen anatomo clinical properties of the tumour was also analysed. The activity of cathepsin D was found to be statistically significantly higher both in the neoplastic tissue cytosol and homogenate, compared to the cytosol and homogenate of adjacent healthy tissue. No correlation was noted between the activity of cathepsin D in neoplastic cells and other parameters analysed. PMID- 11780578 TI - The diagnosis and surgical management of diseases of the adrenal glands. AB - The authors present their own experience in the diagnosis and management of adrenal tumours and cysts. During the years 1980-2000, 74 patients were underwent surgical treatment. Of this group, 23 had Cushing's syndrome, 19 phaeochromocytomas, 4 Conn's syndrome, 2 virilising tumours, 2 adenocarcinomas, 2 ganglioneuromas, 7 adrenal cysts, 8 adenomas, 3 adenocortical carcinomas, 2 nodular hypertrophies, 1 myelolipoma and 1 liposarcoma. Treatment was effective in 73 (98.6%) of patients. We recommend the transperitoneal approach which allows the visual evaluation of both adrenals and extra adrenal tissue. We regard surgical intervention as being the only effective method of treating adrenal tumours. PMID- 11780579 TI - Tumour necrosis factor and cancer treatment: a historical review and perspectives. AB - At the end of 19th century William Coley, a New York surgeon, was the first to describe necrosis of the tumour induced by bacterial toxins. In 1975, a protein responsible for the induction of this process was identified and called tumor necrosis factor alpha (TNF-alpha). The application of recombinant DNA methodology has resulted in the production of large quantities of highly purified recombinant human TNF-alpha for both preclinical and clinical studies. Although TNF-alpha is still viewed by most investigators as a selective antitumor agent, its pleiotropic activities are admirably illustrated by numerous newly discovered functions of TNF-alpha in the host defenses, inflammation, pathogenesis, regulation of gene expression and differentiation. This literature survey discusses the discovery of TNF-alpha and its potential applications to antitumour therapy. PMID- 11780580 TI - Alpha-1-antitrypsin phenotypes in patients with ankylosing spondylitis. AB - Alpha-1-antitrypsin (A1AT) is the most important plasma inhibitor of serine proteases present in numerous polymorphic varieties. It is suggested that phenotypes may be found more frequently in the connective tissue diseases. The purpose of our study was to determine individually the A1AT phenotype and to establish the prevalence rate of A1AT phenotypes in the serum of 52 patients with ankylosing spondylitis (AS). The preliminary analysis of the data indicates that a different prevalence pattern of A1AT phenotypes is found in patients with AS in comparison with a control group. The MM2 phenotype, which is responsible for both normal A1AT concentration in serum and its function, is less frequent in these patients. The deficit phenotypes causing abnormal A1AT concentration were not found in AS patients, which may be due to the relatively small number of patients. PMID- 11780581 TI - Plasma and mucosal prostaglandin E2 as a surrogate marker of ulcerative colitis activity. AB - BACKGROUND: Enhanced production of prostaglandin E2 was observed in the course of inflammatory bowel diseases. The study was undertaken to determine whether mucosal and plasma concentrations of PGE2 can be considered as a surrogate marker of bowel inflammation activity in patients with ulcerative colitis. METHODS: Prostaglandin E2 concentration was measured with an EIA in biopsies of rectal mucosa and plasma of 79 patients with ulcerative colitis and 12 controls. Endoscopic picture was scored and compared with plasma and mucosal PGE2, as well as with possible laboratory markers of the disease activity, including C-reactive protein, albumin, gamma-globulin, haemoglobin concentrations, and sedimentation rate, white blood count and platelets count. RESULTS: Plasma and mucosal PGE2 demonstrated in ulcerative colitis exceeded control level over five and three fold respectively. They increased depending on the scored degree of mucosal injury, demonstrated through significant positive correlation (r = 0.437 and r = 0.525). Among other possible laboratory markers of the disease activity, only sedimentation rate revealed significant correlation (r = 0.288). CRP demonstrated weak association with the disease activity and there was almost lack of any association in respect to white blood count, and albumin or gamma-globulin concentrations. CONCLUSION: These data confirm possible usefulness of plasma or mucosal PGE2 measurement in patients with ulcerative colitis as a possible marker of inflammation. Moreover, as a prognostic factor it can reduce the number of endoscopic procedures. PMID- 11780582 TI - Isolation of MUC 1 antigen from human gastric juice. AB - Episialin (MUC 1 antigen) is a membrane bound mucin. It is located on the surface of the epithelium. It can also be detected in soluble form in body fluids. In our paper we present method of the purification of this antigen from human gastric juice. MUC 1 antigen was isolated from human gastric juice by the gel filtration on Sepharose 4B column and affinity chromatography with HMFG-1 antibody coupled to CNBr activated Sepharose 4B. Using presented methods for purification of MUC 1 antigen from gastric juice we received after immunostaining one diffuse band of about 400 kDa molecular weight. Our results revealed that presented method of isolation of MUC 1 antigen from gastric juice is a valuable and sufficient procedure for purification of soluble form of this antigen. PMID- 11780584 TI - A rare localization of Hodgkin's disease in the breast--a case report. AB - In this paper we present a rare localization of Hodgkin's disease--in the breast. An awareness of such unusual clinical presentation of Hodgkin's disease is important to prevent a delay in diagnosis and treatment. PMID- 11780583 TI - Relationship between TNF-alpha, IL-6 and their soluble receptors in the cultures of human PMN, PBMC and WBC. AB - Numerous clinical and experimental studies have focused on the measurement of cytokines as well as their regulatory proteins, produced by peripheral blood mononuclear cells (PBMC) or whole blood cells (WBC) as parameters for the immune cellular potential of the host. Much less is known about the contribution of neutrophils or polymorphonuclear leukocytes (PMN) in generating TNF-alpha and IL 6 as well as their soluble receptors. In order to compare the role of PMN to other cells of peripheral blood in the secretion of these mediators we estimated here their release by PMN, PBMC and WBC taken from the same blood samples of healthy donors. A significant similarity in the release of IL-6 by PMN, PBMC and WBC indicate that PMN could be an important source of this cytokine in inflammatory and immune reactions. Although PMN exhibited a lower ability to secretion of sIL-6R, TNF-alpha and sTNFRs, the similar relationships between them in the culture supernatants of PMN, PBMC and WBC indicate on the same ability for contribution in reactions controlled by IL-6 and TNF-alpha. Data presented here in data suggest the possibility of employing PMN to examination the cellular innate response of the host. PMID- 11780585 TI - Aryltriazole C-nucleosides with affinity to certain DNA sequence. II. Synthesis of 4-(beta-D-erythrofuranosyl)-2-(4-methyl-3-nitrophenyl)-1,2,3-triazole from D psicose. AB - The paper describes the synthesis of 4-(beta-D-erythrofuranosyl)-2-(4-methyl-3 nitrophenyl)-1,2,3-triazole. This compound is a starting material for synthesis of C-nucleosides, having a potential affinity with G-C base pair. PMID- 11780587 TI - Depth electroencephalography in selection of refractory epilepsy for surgery. Our experience with the suboccipital approach. AB - Despite new diagnostic tools, the precise localisation of an epileptic focal discharge remains an important step in the surgical treatment of epilepsy. Conventional EEG not always gives enough information to decide about surgery and more invasive methods have to be used. Epidural, subdural, and intra parenchymatous electrodes have been used to come closer to the epileptic foci. Superficial hemispheric foci are well recorded by conventional epidural or subdural, strip or grid electrodes. Deeper foci, located in the medial temporal lobe or limbic areas are much more difficult to access from surface electrodes and other methods have to be used. Stereotactic placed multielectrodes and foramen ovale electrodes are most commonly implanted. Since 1986 we have used multi-contact cylindrical soft subdural electrodes. At the beginning we made the electrodes in our Department. Later on they were commercially available. In our Clinic the electrodes are usually introduced via a suboccipital approach and directed to the medial aspects of the temporal lobes until the temporal poles on both sides. Usually a median electrode located in the interhemispheric fissure, and covering gyrus cinguli is also placed. Out of 60 procedures done for different kinds of epilepsy, including cases with tumour or other surgical epileptogenic lesions, a total of 14 patients with genuine temporal lobe epilepsy have been studied and operated by this method. The advantages of the method as compared to stereotactic intraparenchymatous implanted electrodes are: less risk of bleeding and the fact that the brain tissue in those sensitive areas remains intact. Compared to foramen ovale electrodes our technique covers larger area of the temporal lobes and allows to insert a medial limbic electrode, but demands 2 burr holes. A further advantage of our technique is that the electrodes remain in place until surgery, allowing for their use as anatomical landmarks for tailoring the extension of the resection. This approach has been found to be simple, safe and reliable. A further improvement may be the simultaneous use of PEG epidural electrodes to obtain an overall view of the electrical activity of the brain including surface, deep temporal and midline cortical areas. PMID- 11780586 TI - [Surgical outcome of temporal lobe epilepsy]. AB - Results of the surgical treatment of temporal lobe epilepsy--Authors present their own experience in the surgical treatment of temporal lobe epilepsy. 403 patients were operated upon. The age of the patients was not limited. The beginning of the epilepsy was in most cases in early childhood, however the conservative treatment was continued for a very long time, usually over 10 years. The modern diagnostic tools, especially MRI, make it possible to diagnose the temporal epileptic focus more often, than previously, especially in cases with morphological substrate. Temporal lobectomy with amygdalo-hippocampectomy was performed. The follow-up was at least 3 years after surgery. Outs of 343 patients examined in this period 175 were cured, without seizures after surgery. Next 61 patients had no more than 2 small attacks a year. So in 69% of patients the result was very good or satisfactory. The neuropsychological investigation revealed that in most patients the IQ improved. Their quality of life improved markedly according to their own opinion. PMID- 11780588 TI - [Glutamate receptor antagonists as potential antiepileptic drugs]. AB - Numerous antagonists of glutamate, belonging to N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists, were demonstrated to display anticonvulsant activity in various models of experimental epilepsy. Also, the glutamate antagonists enhanced the protective activity of conventional antiepileptic drugs against maximal electroshock-induced seizures in mice. However, some combinations of conventional antiepileptics with NMDA receptor antagonists resulted in profound adverse effects. In contrast, the antagonists from the non-NMDA receptor group potentiated the anticonvulsant activity of conventional antiepileptics, with no side-effects being observed. In some cases, the combined treatments were superior to the antiepileptic drugs alone, as regards adverse effects. In no case, glutamate antagonists affected the plasma levels of antiepileptic drugs. These data seem to indicate that non-NMDA receptor antagonists bear more important clinical potential as adjuvant antiepileptic drugs. PMID- 11780589 TI - Pharmacotherapy of epilepsy. AB - Epilepsy represents the most common serious neurologic complications affecting approximately 1% of the world's populations. Although standard therapy permits control of seizures in about 80% of affected individuals, millions of global population have uncontrolled epilepsy. In the United States alone, the uncontrolled epilepsy represents more than 500,000 people. In the past decade, we have witnessed an array of new generations of antiepileptic drugs (AEDs) with more favorable pharmacokinetics and pharmacodynamic parameters, providing wider option to neurologists/epileptologists for more clinically effective and safer treatment. This was in part due to our better understanding of neural and molecular mechanisms in recurrent seizures. The new generations of AEDs currently include tiagabine, vigabatrin, lamotrigine, zonisamide, felbamate, oxacarbazine, topiramate, and gabapentine. There will be newer generations of AEDs being developed by pharmaceutical companies in United States, Japan, and European countries and will enter into global market sometimes during this decade. Although more clinical trails concerning the existing new generations of AEDs are needed, the available data suggest that in principal, these agents offer advantageous in terms of seizure control, fewer side effects and drug-drug interactions compared to traditional agents phenytoin, carbamazepine, phenobarbital, and valproate. The new generations of AEDs are significantly more expensive than the traditional agents. The two most clinical concerns over the use of traditional AEDs include (i) deleterious adverse effects and (ii) drug interactions, however, these agents are widely used in the third world countries. A thorough understanding of clinical pharmacology of both traditional and new antiepileptic agents will enable clinicians to have better appreciation of their clinical use and the treatment outcome, especially when the traditional agents are pharmacoeconomically preferred. Clinical pharmacology of AEDs is a vast science in medicine consisted of two principal arms, (i) pharmacokinetics and (ii) pharmacodynamics. This article briefly describes the pros and cons of common AEDs in practice, with more emphasis on new AEDs. PMID- 11780590 TI - [Disturbances of glucose metabolism in epilepsy and other neurodegenerative diseases]. AB - Disturbances of glucose metabolism in epilepsy and other neurodegenerative diseases. Impairment of glucose and acetyl-CoA metabolism is a characteristic feature of several degenerative brain diseases. Presented paper provides experimental evidences that NO, aluminum and thiamine deficiency result in concordant disturbances in acetyl-CoA campartmentalisation as well as in nonquantal and quantal acetylcholine release in rat brain nerve terminals. Our findings indicate that simultaneous depression of acetyl-CoA synthesis and its increased utilisation for acetylcholine synthesis in the presence of neurotoxic factors is likely to make brain cholinergic neurones particularly prone to neurodegeneration. PMID- 11780591 TI - [Effects of corticosteroids on seizures and neurotoxicity]. AB - Neurosteroids are precursors or metabolites of steroid hormones, which influence the excitability of central nervous system via nongenomic mechanism. Neurosteroids which are positive allosteric modulators of GABAA receptors, show anticonvulsant effects in a variety of animal models of epilepsy. Furthermore, some neurosteroids can prevent excitatory amino acid- and oxidative stress induced neuronal damage both in vivo and in vitro. The efficacy and low intrinsic toxicity of neurosteroids, suggest their potential use in therapy of some neurological diseases. PMID- 11780592 TI - [Surgical treatment of symptomatic surgery in children using classical techniques versus extended lesion surgery and focal lesion surgery]. AB - In a series of 2400 children 80% had favourablly responded to medication, 60% are seizure-free and in 20% there was significant improvement in further 20% any medication has failed. 200 children have been operated upon because of epilepsy resistant to pharmacological treatment., in 80 = 3% classical methods of removal of the epileptogenic substrate (lobectomies, hemisphereectomies, topectomies and disconnective techniques) have been applied. In 120 cases verified symptomatic epilepsy associated with the leading symptom of untreatable attacks due to aetiological lesions as benign neoplasms, scars, angiomas, cysts lesionectomies extended by focectomies have been performed (with a seizure result of 77.6%). The pathological substrate of the epileptic excitation area has been localized and tailored by repeated diagnostic associated bioelectrical and neuroradiological procedures (EEG, BEAM, SPECT, NMR) Since at least many years after the operation nearly 2/3 of the patients remain seizure-free our methods have proven themselves as a useful and noninvasive tool for the focus localization. The plasticity of the developing brain has resulted in a very impressively favourable outcome particularly in the seizure-free children as far as it concerns the intellectual level and social validation. On neurological testing there was no deterioration. On psychological and neurolinguistic exploration there was an evident improvement of gnostic orientation and quality of life; speech functions are fairly good for current and fluent communication. PMID- 11780593 TI - [The mechanisms of neuronal death and advances in the neural protection in epilepsy]. AB - Epilepsias are chronic central nervous system diseases which manifest by recurrent seizures. They may be classified into channelopathies resulting from mutations of ionic channels or receptors for neurotransmitters, and epilepsias which are secondary to cortical damage and result from the reconstruction of cortical neural networks. Chronic or generalized seizures initiate processes called the "excititoxic cascade" the effector side of which, quite similar to that of the "ischemic cascade", may lead to neuronal death through either apoptosis or necrosis. Therefore, complementing pharmacological treatment of epilepsia with neuroprotective substances such as free radical scavenger or CDP choline which blocks the activation of phospholipase A2 may be indicated. PMID- 11780594 TI - [Gabaergic hypothesis of epilepsy and clinical experience: controversial actions of the new generation gabamimetic antiepileptic drugs]. AB - Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring significant qualitive change in the possibilities of pharmacotherapy. PMID- 11780595 TI - HIV among people with chronic mental illness. AB - Rates of HIV infection, STDs, and sexual and drug-use risk behaviors are high among people with severe mental illness. Clinicians often are in the best position to connect psychiatric patients to the particular HIV-related services they need. These may include prevention interventions, risk assessment, antibody test counseling, and medical care. This review article describes the AIDS epidemic and its underpinnings in this population in an effort to help clinicians to recognize when their patients are at risk for acquiring or transmitting the virus and to intervene appropriately and effectively with an array of relevant services. The importance of training to enhance clinicians' skills and comfort in delivering these services is emphasized. The lives and well-being of psychiatric patients are threatened by the AIDS epidemic, and there is much clinicians can do to minimize the devastating impact of HIV and AIDS on clients in hospitals, clinics, and other psychiatric treatment settings. PMID- 11780596 TI - Psychopharmacological treatment of patients with HIV and AIDS. AB - Psychopharmacological treatment of patients with HIV/AIDS is an important aspect of managing distress and enhancing quality of life. This article reviews the psychopharmacological management of depression, anxiety, mania, and psychosis in the context of HIV/AIDS, with a discussion of psychotropic-antiretroviral drug interactions. While psychopharmacological management of HIV/AIDS patients may be complex, there is a substantial amount of clinical and research information describing both conventional and novel approaches that are safe and effective. PMID- 11780597 TI - Clinical management of psychiatric disorders in patients with HIV disease. AB - HIV disease presents considerable challenges that can affect adjustment and health-related behaviors. This article provides an overview of clinical considerations in the treatment of comorbid psychiatric disorders and problems in adjustment in HIV patients. First, the research literature is reviewed with respect to biomedical, intrapersonal, and psychosocial factors associated with HIV-related psychological adjustment and psychiatric complications. Next, a brief description is presented regarding prevalence and types of co-occurring psychiatric disorders seen in HIV patients. The article concludes with a discussion of clinical assessment and treatment considerations for psychiatric clinicians who work with HIV patients. PMID- 11780598 TI - Challenges in the management of the HIV patient in the third decade of AIDS. AB - The epidemic of AIDS has been increasingly recognized as a major health and socioeconomic problem, not only in the United States or Africa, but also the rest of the world. The face of the epidemic has changed. The role that mental health providers play has also significantly grown as the epidemic continues on. Prior to the introduction of Highly Active Anti-Retroviral Therapy (HAART) and other advances in HIV care, the patients faced issues that related to death and dying. These advances brought with them renewed hope and resurrected lives. The patients fought with issues related to living new lives with HIV no longer an imminent death threat. In the third decade of AIDS, the struggles of the post-HAART era continue but bring with it more challenges. Mental health providers need to familiarize themselves with these issues so that they can better help HIV patients cope with this devastating disease. PMID- 11780599 TI - Characteristics of assaultive psychiatric patients: ten year analysis of the Assaulted Staff Action Program (ASAP). AB - Nearly thirty years of published research has documented the continuing presence of patient assaults on staff. These studies have included the traditional male patient with a diagnosis of schizophrenia and histories of violence and substance use disorder and the newer female, personality-disordered individual. This study reports on a ten-year longitudinal analysis of assaultive patients in one public sector mental healthcare system during a period which included the national shift toward managed care initiatives. Data were gathered in the context of the Assaulted Staff Action Program, a crisis intervention program for staff victims. Patient assailants in both inpatient and community settings included both the traditional and newer personality-disordered individuals. The majority of assailants were females. Managed care initiatives appeared to have had little impact on type of assailants. Implications for safety and treatment are discussed. PMID- 11780600 TI - Twin studies in psychiatry and psychology: science or pseudoscience? AB - Twin studies are frequently cited in support of the influence of genetic factors for a wide range of psychiatric conditions and psychological trait differences. The most common method, known as the classical twin method, compares the concordance rates or correlations of reared-together identical (MZ) vs. reared together same-sex fraternal (DZ) twins. However, drawing genetic inferences from MZ-DZ comparisons is problematic due to methodological problems and questionable assumptions. It is argued that the main theoretical assumption of the twin method -known as the "equal environment assumption"--is not tenable. The twin method is therefore of doubtful value as an indicator of genetic influences. Studies of reared-apart twins are discussed, and it is noted that these studies are also vulnerable to methodological problems and environmental confounds. It is concluded that there is little reason to believe that twin studies provide evidence in favor of genetic influences on psychiatric disorders and human behavioral differences. PMID- 11780601 TI - Keynote debate. The presidential election and its effect on health care. PMID- 11780602 TI - Health Management Awards 2001. Leading lights. PMID- 11780603 TI - Epithelial desquamation in asthma. PMID- 11780604 TI - CM plays a critical role in disaster planning. PMID- 11780605 TI - Certification among case managers on the upswing. PMID- 11780606 TI - Lifeline Registry: collaborative evaluation of endovascular aneurysm repair. AB - PURPOSE: The purpose of this study is to collect and analyze long-term outcome data on the safety and effectiveness of endovascular grafts used in abdominal aortic aneurysm repair in the United States and Canada. We aimed to help define appropriate patients for endograft therapy and to evaluate long-term device performance and patient outcome, thereby contributing to improving the care of patients with abdominal aortic aneurysms. METHODS: Data entered in the Registry include the electronic data collected under the endovascular graft manufacturers' clinical trials, prospective follow-up data of patients enrolled in these trials, both from the clinical centers and from interviews conducted at New England Research Institutes, and explant data, obtained primarily from analyses conducted by the Registry central pathology laboratory. SCOPE: The Registry records and analyzes the long-term follow-up data of patients in the clinical trials that lead to devices approved by the Food and Drug Administration. The Registry has also launched a feasibility study to expand the Registry to include patients receiving commercial endovascular grafts, the devices available following Food and Drug Administration marketing approval. PMID- 11780608 TI - My brilliant career--mental health. Soldiering on. PMID- 11780609 TI - Bibliography. Current world literature. Leukocyte biology. PMID- 11780607 TI - Second AAPS-NIH frontier symposium 1999: membrane transporters and drug therapy. American Association of Pharmaceutical Scientists. PMID- 11780610 TI - An adventure in excellence. 1962. PMID- 11780611 TI - [History of the foundation of the School of Medicine of the University of Puerto Rico]. PMID- 11780612 TI - KJ Smith, M Theal, A Mulji. Pericarditis presenting and treated as an acute anterospetal myocardial infarction. Can J Cardiol 2001;17(7):815-817. PMID- 11780613 TI - Radiation exposure of civilian airline crew members and associated biological effects due to the atmospheric ionizing radiation environment. AB - A study, currently in progress, on the radiation exposure and the associated biomedical effects due to the atmospheric ionizing radiation environment for the Italian civilian aviation flight personnel is sketched. After a presentation of the considered data sources, a description of the cohort is given, in terms of criteria for eligibility, and cohort construction, size and composition. Then the protocol for the Italian study is presented: the various ways of investigating the exposure and the health status of past and currently employed aircrew members and follow-up procedures are shown. An overview is given of the data management and processing philosophy with regards to flight routes, radiation dose evaluation along the flight path and exposure matrix building, as adopted in the Italian study. Potential side studies of interest are also shown. PMID- 11780614 TI - Radiation-dependent apoptosis on cultured thyroid cells. AB - Aim of this investigation is the study of the modifications and the DNA damage occurring in thyroid cells exposed to radiation. The FRTL-5 rat thyroid cell strain has been chosen for this study. Objects of this research are both Ionizing radiation, of fundamental interest for space missions, and the UV radiation, (also mutagen and frequent cause of several cancer forms). The present study of UV radiation represents a preliminarily tool to investigate the biological radiation damage. FRTL-5 cells have been irradiated with doses of UV-C (254 nm wavelength) ranging from 15 to 80 Joule/m2. The DNA damage has been analyzed with the 'DNA ladder by gel electrophoresis' technique. DNA has been extracted at 24 and 48 hours from irradiation. At 24h the apoptotic process is not detectable. At 48 h from irradiation, cells show the characteristic signs of apoptosis. The lower dose to which the apoptotic process is detectable, corresponds to 20 Joule/m2. At the higher doses a bigger percentage of cells undergoes apoptosis. These data confirms that the FRTL-5 biological system is particularly suitable for further studies on the biological mechanisms of radiation damage. PMID- 11780615 TI - X-ray-induced chromosome aberrations in human lymphocytes in vitro are potentiated under simulated microgravity conditions (Clinostat). AB - The influence of simulated microgravity weightlessness on the outcome of radiation-induced chromosomal aberrations was investigated using the clinostat as a tool to simulate weightlessness conditions. Treatments were performed in the G0 phase of human lymphocytes with 1.5 Gy of X-rays alone or in combination with the DNA synthesis inhibitor of 1-beta-D-arabinofuranosylcytosine (ara-C) to check also for possible specific radiation-induced DNA repair processes impairment (excision repair caused by base damage) under microgravity conditions. The results obtained, which confirmed previous findings, showed significantly higher increases of aberrant cells and hence total number of aberrations compared to the parallel treatments performed 'on ground'. For what concern ara-C its contribution in terms of potentiation in the induction of aberrant cells was equivalent in absolute terms under simulated microgravity conditions and 'on ground' indicating that excision repair caused by base damage and inhibited by ara-C is not affected by simulated microgravity. A possible explanation for this outcome could quote two major factors: i) Enhanced probability that under simulated microgravity conditions the reactive DSB are spatially brought together to better interact, hence increasing the probability of mis-rejoining. ii) Alternatively chromatin structure could be modified under simulated microgravity conditions generating different quality and quantities of DNA lesions compared to treatments performed 'on ground'. PMID- 11780616 TI - A device to study the effect of space radiation on photosynthetic organisms. AB - This research concerns the study of the effects of ionising space radiation on the oxygen-evolving activity of algae and cyanobacteria, focusing our attention on Photosystem II (PS-II), the oxygen-evolving complex. These microorganisms as higher plants, can use light energy to split water molecules and evolve oxygen in a process that produce storable energy-rich products from atmospheric carbon dioxide. Algae and cyanobacteria which can grow in the presence of nutrients and carbonate are expected to be utilised to maintain an oxygen-atmosphere and to constitute biomass in space shuttles. Irradiation was performed in gamma 60Co sources of different activities; fluorescence techniques in vivo and SDS-PAGE analysis in vitro were used to determine PS-II efficiency during radiation stress. We determined the radiation target on PS-II by immunoblot. We built a miniaturised growth box that preserves constant pressure and temperature to measure automatically photosynthetic activity by a fluorescence sensor, directly in space during a mission in an ASI balloon. PMID- 11780617 TI - Influence of the shielding on the space radiation biological effectiveness. AB - A research program in space radiobiology is described in this report. The program is focused on the effect of the shielding on the biological effects of heavy ions. Both experiments and models are included in the program. Experiments aim to determine genetic effects of heavy ions with or without shielding. Mathematical models, based on Monte Carlo codes, will be used to interpret the biological results. The final goal is to get a feasible model able to predict the radiation induced biological damage in space, given the free-space radiation field and the space vessel shielding. The grant is supported by the Italian Space Agency (ASI), and involves Italian radiation biophysics groups (Universities of Milan and Naples, National Institute of Health in Rome), in collaboration with NASA (USA), NIRS (Japan), CERN (Switzerland), Brookhaven National Laboratories (USA), and TERA (Italy). PMID- 11780618 TI - Mechanistic bases for modelling space radiation risk and planning radiation protection of astronauts. AB - The approaches generally adopted for planning radiation protection in ground based facilities cannot be applied straightforward for astronaut protection in space. Indeed in such extreme conditions, modelling methods and shielding design must be based on a detailed mechanistic knowledge of the peculiar astronauts irradiation conditions. Great help can derive from mechanistic modelling, generally aimed to better understand the intermediate steps leading from the initial energy depositions to different biological endpoints, up to organ and organism level. In the present work, criteria will be illustrated for using mechanistic approaches in developing practical tools for astronauts radioprotection, once the external field and the interaction cross sections with the spacecraft walls are known; particular attention will be given to the treatment of mixed fields. Techniques for integrating into condensed-history codes stochastic information provided by event-by-event simulations will be presented. PMID- 11780619 TI - An overview of recent charged-particle radiation biology in Italy. AB - Radiobiology with charged particles is being carried out in Italy since several decades, starting with the experiments with protons in Milan. Later, also other groups entered the field, such as those in Naples, in Legnaro (LNL) and in Rome. In the last 10-15 years the activities in the field began to grow in a significant way. This happened in concomitance with the involvement of various researchers and Institutions in European and international projects devoted to radiation protection aspects, such as those aimed at elucidating and modelling radiation action mechanisms (EC/EU) and those aimed at radiation protection in space (NASA). A special role has been played since then by the Laboratori Nazionali di Legnaro of the INFN, where a radiobiology facility for low energy light ions was set up and operated in 1985. A formidable stimulus for charged particle radiobiology was more recently given by the onset of plans for developing hadrontherapy Centres in Italy. The TERA Foundation first, and than the TOP Project at the Istituto Superiore di Sanita, at the same time favoured the spreading in Italy of radiobiology research with charged particles and encouraged co-operation among various groups. The Italian radiobiology community, though relatively small, developed a number of valuable activities with charged particles, mostly at the cellular and molecular levels, that span from mechanisms of radiation action to radiation protection in space and to therapy with charged hadrons. In this article, due to space limitations, we have just been able to list the present activities and to briefly review some research that forms a common background for the various areas. This includes the work on Chinese hamster V79 cells irradiated with light ions at LNL, that provided extensive data on the relationships between radiation quality, molecular damage and cellular effects, and the related work aimed at possible interpretation by mechanistic models. It appears that the multiplicity of objectives does not represent a factor of weakness for the relatively small Italian radiobiology community. Synergistic effects have been found because the basic radiobiology is the same for different areas such as radiation protection and hadrontherapy, and because the expertise and the methods developed for a given purpose may find useful applications in others. Though it is difficult to forecast the future development in Italy of the various areas that will take advantage of charged-particle radiobiology, it is expected that hadrontherapy and space radiation protection together, independently of their relative weight, will be important driving forces for the future development of the field in our Country. PMID- 11780620 TI - European dosimetry activities for the ISS. AB - In cooperation with the University of Kiel, the University GH of Siegen, the Physikalisch-Technische Bundesanstalt in Braunschweig, the Atomic Energy Research Institute in Budapest and the Institute for Biomedical Problems in Moscow, DLR performed measurements of the radiation environment inside and outside spacecrafts on numerous missions with the main objective to determine as precise as possible the radiation exposure of the astronauts. This report comprises some selected results of recent manned missions and indicates where improvements should be achieved and closes with the description of future measurements planned onboard the International Space Station (ISS). PMID- 11780621 TI - Radiation measurements on the International Space Station. AB - The International Space Station (ISS) is becoming a reality with the docking of the Russian Service module (Zarya) with the Unity module (Zaveda). ISS will be in a nominal 51.65-degree inclination by 400 km orbit. This paper reviews the currently planned radiation measurements, which are in many instances, based on experiments previously flown on the Space Shuttle. Results to be expected based on Shuttle measurements are presented. PMID- 11780622 TI - High LET radiobiology at NIRS--current status and future plan. AB - HIMAC synchrotron radiates not only physical beams to cancer patients but also attractiveness to healthy scientists. Our persistent interest to clarify the biologically significant damage caused by high LET radiation needs multilayered approaches including molecular, cellular and tissue levels; all the levels being deeply integrated with physics. The outcome of our research is important for (1) promoting the evidence-based radiotherapy and (2) clarifying the radiation risk in space. We are currently conducting the following experiments; LET-RBE relationship for cell kills, chromatin damages and mutation induction, mitochondrial damages, brain damages at cellular and behavioral level, and fractionated irradiation to skin, gut and tumors. Capacity of cells to repair DNA damages may play an important role in space radiation environment that is characterized as a long-term exposure at low dose rates with mixed LET radiation. Experiments using cells deficient of DNA repair suggested that a process of damage recognition is critical for biological effectiveness of high LET radiation. Specific for space radiation research, we have started a long-term exposure of cultured cells to secondary beams produced at the HIMAC Biology Room. A future plan using HIMAC beams is described. PMID- 11780623 TI - Ricky Ray Hemophilia Relief Fund Program. Adoption of interim final rule as final rule with amendments. AB - This document adopts the Ricky Ray Hemophilia Relief Fund Program interim final rule as a final rule with amendments. This final rule facilitates the petitioning process where health care history can be certified by physician assistants as well as by physicians or nurse practitioners; details the procedures by which the Secretary may resolve issues of eligibility or payment raised by a petition; ensures that payments made for the benefit of minors and other individuals who do not have the legal capacity to receive the payments are used for their benefit; and allows additional time for petitioners who are having difficulty obtaining needed medical or legal documentation to complete their petitions. PMID- 11780624 TI - Medicare program; negotiated rulemaking: coverage and administrative policies for clinical diagnostic laboratory services. Final rule. AB - This final rule establishes national coverage and administrative policies for clinical diagnostic laboratory services payable under Medicare Part B to promote Medicare program integrity and national uniformity, and simplify administrative requirements for clinical diagnostic laboratory services. This rule addresses public comments received on the proposed rule that was published March 10, 2000. A Negotiated Rulemaking Committee (the Committee) developed the policies as directed by section 4554(b)(1) of the Balanced Budget Act of 1997 (the BBA). PMID- 11780625 TI - A mechanism for stop codon recognition by the ribosome: a bioinformatic approach. AB - Protein synthesis in ribosomes requires two kinds of tRNAs: initiation and elongation. The former initiates the process (formylmethionine tRNA in prokaryotes and special methionine tRNA in eukaryotes). The latter participates in the synthesis proper, recognizing the sense codons. Synthesis is also assisted by special proteins: initiation, elongation, and termination factors. The termination factors are necessary to recognize stop codons (UAG, UGA, and UAA) and to release the complete protein chain from the elongation tRNA preceding a stop codon. No termination tRNA capable of recognizing stop codons by their anticodons is known. The termination factors are thought to do this. In the large ribosomal RNA, we found two sites that, like tRNAs, contain the anticodon hairpin but with triplets complementary to stop codons. One site is hairpin 69 from domain IV; the other site is hairpin 89, domain V. By analogy, we call them termination tRNAs: Ter-tRNA1 and Ter-tRNA2, respectively, even though they transport no amino acids, and suggest that they directly pair to stop codons. The termination factors only aid in this recognition, making it specific and reliable. A strong argument in favor of our hypothesis comes from vertebrate mitochondria. They are known to acquire two new stop codons, AGA and AGG. In the standard code, these are two out of six arginine codons. We revealed that the corresponding anticodons, UCU and CCU, have evolved in Ter-tRNA1 of these mitochondria. PMID- 11780627 TI - Escherichia coli RNase M is a multiply altered form of RNase I. AB - RNase M, an enzyme previously purified to homogeneity from Escherichia coli, was suggested to be the RNase responsible for mRNA degradation in this bacterium. Although related to the endoribonuclease, RNase I, its distinct properties led to the conclusion that RNase M was a second, low molecular mass, broad specificity endoribonuclease present in E. coli. However, based on sequence analysis, southern hybridization, and enzyme activity, we show that RNase M is, in fact, a multiply altered form of RNase I. In addition to three amino acid substitutions that confer the properties of RNase M on the mutated RNase I, the protein is synthesized from an rna gene that contains a UGA nonsense codon at position 5, apparently as a result of a low level of readthrough. We also suggest that RNase M is just one of several previously described endoribonuclease activities that are actually manifestations of RNase I. PMID- 11780626 TI - A genome-wide survey of RS domain proteins. AB - Domains rich in alternating arginine and serine residues (RS domains) are frequently found in metazoan proteins involved in pre-mRNA splicing. The RS domains of splicing factors associate with each other and are important for the formation of protein-protein interactions required for both constitutive and regulated splicing. The prevalence of the RS domain in splicing factors suggests that it might serve as a useful signature for the identification of new proteins that function in pre-mRNA processing, although it remains to be determined whether RS domains also participate in other cellular functions. Using database search and sequence clustering methods, we have identified and categorized RS domain proteins encoded within the entire genomes of Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae. This genome wide survey revealed a surprising complexity of RS domain proteins in metazoans with functions associated with chromatin structure, transcription by RNA polymerase II, cell cycle, and cell structure, as well as pre-mRNA processing. Also identified were RS domain proteins in S. cerevisiae with functions associated with cell structure, osmotic regulation, and cell cycle progression. The results thus demonstrate an effective strategy for the genomic mining of RS domain proteins. The identification of many new proteins using this strategy has provided a database of factors that are candidates for forming RS domain-mediated interactions associated with different steps in pre-mRNA processing, in addition to other cellular functions. PMID- 11780628 TI - Increased sensitivity to protein synthesis inhibitors in cells lacking tmRNA. AB - tmRNA (also known as SsrA or 10Sa RNA) is involved in a trans-translation reaction that contributes to the recycling of stalled ribosomes at the 3' end of an mRNA lacking a stop codon or at an internal mRNA cluster of rare codons. Inactivation of the ssrA gene in most bacteria results in viable cells bearing subtle phenotypes, such as temperature-sensitive growth. Herein, we report on the functional characterization of the ssrA gene in the cyanobacterium Synechocystis sp. strain PCC6803. Deletion of the ssrA gene in Synechocystis resulted in viable cells with a growth rate identical to wild-type cells. However, null ssrA cells (deltassrA) were not viable in the presence of the protein synthesis inhibitors chloramphenicol, lincomycin, spiramycin, tylosin, erythromycin, and spectinomycin at low doses that do not significantly affect the growth of wild-type cells. Sensitivity of deltassrA cells similar to wild-type cells was observed with kasugamycin, fusidic acid, thiostrepton, and puromycin. Antibiotics unrelated to protein synthesis, such as ampicillin or rifampicin, had no differential effect on the deltassrA strain. Furthermore, deletion of the ssrA gene is sufficient to impair global protein synthesis when chloramphenicol is added at sublethal concentrations for the wild-type strain. These results indicate that ribosomes stalled by some protein synthesis inhibitors can be recycled by tmRNA. In addition, this suggests that the first elongation cycle with tmRNA, which incorporates a noncoded alanine on the growing peptide chain, may have mechanistic differences with the normal elongation cycles that bypasses the block produced by these specific antibiotics. tmRNA inactivation could be an useful therapeutic target to increase the sensitivity of pathogenic bacteria against antibiotics. PMID- 11780629 TI - The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. AB - A major pathway of mRNA turnover in eukaryotic cells initiates with deadenylation, leading to mRNA decapping and subsequent 5' to 3' exonuclease digestion. We show that a highly conserved member of the DEAD box family of helicases, Dhh1p, stimulates mRNA decapping in yeast. In dhh1delta mutants, mRNAs accumulate as deadenylated, capped species. Dhh1p's effects on decapping only occur on normal messages as nonsense-mediated decay still occurs in dhh1delta mutants. The role of Dhh1p in decapping appears to be direct, as Dhh1p physically interacts with several proteins involved in mRNA decapping including the decapping enzyme Dcp1p, as well as Lsm1p and Pat1p/Mrt1p, which function to enhance the decapping rate. Additional observations suggest Dhh1p functions to coordinate distinct steps in mRNA function and decay. Dhh1p also associates with Pop2p, a subunit of the mRNA deadenylase. In addition, genetic phenotypes suggest that Dhh1p also has a second biological function. Interestingly, Dhh1p homologs in others species function in maternal mRNA storage. This provides a novel link between the mechanisms of decapping and maternal mRNA translational repression. PMID- 11780630 TI - A conserved role of a DEAD box helicase in mRNA masking. AB - Clam p82 is a member of the cytoplasmic polyadenylation element-binding protein (CPEB) family of RNA-binding proteins and serves dual functions in regulating gene expression in early development. In the oocyte, p82/CPEB is a translational repressor, whereas in the activated egg, it acts as a polyadenylation factor. Coimmunoprecipitations were performed with p82 antibodies in clam oocyte and egg lysates to identify stage-regulated accessory factors. p47 coprecipitates with p82 from oocyte lysates in an RNA-dependent manner and is absent from egg lysate p92-bound material. Clam p47 is a member of the RCK/p54 family of DEAD box RNA helicases. Xp54, the Xenopus homolog, with bona fide helicase activity, is an abundant and integral component of stored mRNP in oocytes (Ladomery et al., 1997). In oocytes, clam p47 and p82/CPEB are found in large cytoplasmic mRNP complexes. Whereas the helicase level is constant during embryogenesis, in contrast to CPEB, clam p47 translocates to nuclei at the two-cell stage. To address the role of this class of helicase in masking, Xp54 was tethered via 3' UTR MS2-binding sites to firefly luciferase, following microinjection of fusion protein and nonadenylated reporter mRNAs into Xenopus oocytes. Tethered helicase repressed luciferase translation three- to fivefold and, strikingly, mutations in two helicase motifs (DEAD--> DQAD and HRIGR-->HRIGQ), activated translation three to fourfold, relative to MS2. These data suggest that this helicase family represses translation of maternal mRNA in early development, and that its activity may be attenuated during meiotic maturation, prior to cytoplasmic polyadenylation. PMID- 11780631 TI - Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES dependent translation. AB - The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated, at least in part, by elF4G, which bridges the mRNA termini by simultaneous binding the poly(A)-binding protein (PABP) and the cap-binding protein, elF4E. The poly(A) tail also stimulates translation from the internal ribosome binding sites (IRES) of a number of picornaviruses. elF4G is likely to mediate this translational stimulation through its direct interaction with the IRES. Here, we support this hypothesis by cleaving elF4G to separate the PABP-binding site from the portion that promotes internal initiation. elF4G cleavage abrogates the stimulatory effect of poly(A) tail on translation. In addition, translation in extracts in which elF4G is cleaved is resistant to inhibition by the PABP-binding protein 2 (Paip2). The elF4G cleavage-induced loss of the stimulatory effect of poly(A) on translation was mimicked by the addition of the C-terminal portion of elF4G. Thus, PABP stimulates picornavirus translation through its interaction with elF4G. PMID- 11780633 TI - NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila. AB - The conserved family of NXF proteins has been implicated in the export of messenger RNAs from the nucleus. In metazoans, NXFs heterodimerize with p15. The yeast genome encodes a single NXF protein (Mex67p), but there are multiple nxf genes in metazoans. Whether metazoan NXFs are functionally redundant, or their multiplication reflects an adaptation to a greater substrate complexity or to tissue-specific requirements has not been established. The Drosophila genome encodes one p15 homolog and four putative NXF proteins (NXF1 to NXF4). Here we show that depletion of the endogenous pools of NXF1 or p15 from Drosophila cells inhibits growth and results in a rapid and robust accumulation of polyadenylated RNAs within the nucleus. Fluorescence in situ hybridizations show that export of both heat-shock and non-heat-shock mRNAs, as well as intron-containing and intronless mRNAs is inhibited. Depleting endogenous NXF2 or NXF3 has no apparent phenotype. Moreover, NXF4 is not expressed at detectable levels in cultured Drosophila cells. We conclude that Dm NXF1/p15 heterodimers only (but not NXF2 NXF4) mediate the export of the majority of mRNAs in Drosophila cells and that the other members of the NXF family play more specialized or different roles. PMID- 11780632 TI - A 250-nucleotide UA-rich element in the 3' untranslated region of Xenopus laevis Vg1 mRNA represses translation both in vivo and in vitro. AB - Xenopus laevis Vgl mRNA undergoes both localization and translational control during oogenesis. Vg1 protein does not appear until late stage IV, after localization is complete. To determine whether Vg1 translation is regulated by cytoplasmic polyadenylation, the RACE-PAT method was used. Vg1 mRNA has a constant poly(A) tail throughout oogenesis, precluding a role for cytoplasmic polyadenylation. To identify cis-acting elements involved in Vg1 translational control, the Vg1 3' UTR was inserted downstream of the luciferase ORF and in vitro transcribed, adenylated mRNA injected into stage III or stage VI oocytes. The Vg1 3' UTR repressed luciferase translation in both stages. Deletion analysis of the Vg1 3' UTR revealed that a 250-nt UA-rich fragment, the Vg1 translational element or VTE, which lies 118 nt downstream of the Vg1 localization element, could repress translation as well as the full-length Vg1 3' UTR. Poly(A) dependent translation is not necessary for repression as nonadenylated mRNAs are also repressed, but cap-dependent translation is required as introduction of the classical swine fever virus IRES upstream of the luciferase coding region prevents repression by the VTE. Repression by the Vg1 3' UTR has been reproduced in Xenopus oocyte in vitro translation extracts, which show a 10-25-fold synergy between the cap and poly(A) tail. A number of proteins UV crosslink to the VTE including FRGY2 and proteins of 36, 42, 45, and 60 kDa. The abundance of p42, p45, and p60 is strikingly higher in stages I-III than in later stages, consistent with a possible role for these proteins in Vg1 translational control. PMID- 11780634 TI - Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development. AB - We identified a temperature-sensitive allele of small bristles (sbr), the Drosophila ortholog of human TAP/NXF-1 and yeast Mex67, in a screen for mutants defective in mRNA export. We show that sbr is essential for the nuclear export of all mRNAs tested in a wide range of tissues and times in development. High resolution and sensitive in situ hybridization detect the rapid accumulation of individual mRNA species in sbr mutant nuclei in particles that are distinct from nascent transcript foci and resemble wild-type export intermediates. The particles become more numerous and intense with increasing time at the restrictive temperature and are exported very rapidly after shifting back to the permissive temperature. The mRNA export block is not due indirectly to a defect in splicing, nuclear protein import, or aberrant nuclear ultrastructure, suggesting that in sbr mutants, mRNA is competent for export but fails to dock or translocate through NPCs. We conclude that NXF-1 is an essential ubiquitous export factor for all mRNAs throughout development in higher eukaryotes. PMID- 11780635 TI - The specificity of nucleotide removal during RNA editing in Trypanosoma brucei. AB - RNA editing in Trypanosoma brucei produces mature mRNAs by posttranscriptional insertion and deletion of uridylates (Us) by a series of catalytic steps, which include endoribonucleolytic cleavage, 3' terminal addition or removal of Us, and RNA ligation. Preedited mRNA (pre-mRNA) and guide RNA (gRNA) that are mutated at or near the editing site (ES) were used to examine the effects on the specificity of in vitro editing. Sequences that are not predicted to form a gRNA/pre-mRNA base pair immediately 5' to the ES still supported accurate editing. Substitution of a non-U nucleotide at various positions within a stretch of Us that are normally removed from the ES resulted in deletion of only the Us that were 3' to the substituted nucleotide. Overall, ES selection by the endoribonuclease, the specificity of the 3' exoribonuclease for Us, and ligation appear to act in concert to ensure the production of accurately edited RNA. PMID- 11780636 TI - Interactions of mRNAs and gRNAs involved in trypanosome mitochondrial RNA editing: structure probing of an mRNA bound to its cognate gRNA. AB - Posttranscriptional editing of trypanosome mitochondrial messenger RNA is directed by small guide RNAs (gRNAs). Using crosslinking techniques, we have previously shown that the gRNA base pairs to the mRNA via a 5' anchor, whereas its 3' U-tail interacts with upstream purine-rich mRNA sequences. The incorporation of crosslinking data into RNA folding programs produced similar structure predictions for all gRNA/mRNA pairs examined. This suggests that gRNA/mRNA pairs can form common secondary structure motifs that may be important for recognition by the editing complex. In this study, the structure of CYb mRNA crosslinked to gCYb-558 was examined using solution-probing techniques. The mRNA/gRNA crosslinked molecules are efficient substrates for gRNA-directed cleavage. In addition, when the cleavage assay is performed in the presence or absence of additional UTP, the activities of both the U-specific exonuclease and terminal uridylyl transferase (tutase) can be detected. These results indicate that a partial editing complex can assemble and function on these substrates suggesting that the crosslink captured the molecules in a biologically relevant interaction. The structure probing data directly show that the U-tail protects several mRNA bases predicted to be involved in the U-tail-mRNA duplex. In combination with our previous studies, these new data provide additional support for the predicted secondary structure of interacting gRNA/mRNA pairs. PMID- 11780637 TI - Multiple snoRNA gene clusters from Arabidopsis. AB - Small nucleolar RNAs (snoRNAs) are involved in precursor ribosomal RNA (pre-rRNA) processing and rRNA base modification (2'-O-ribose methylation and pseudouridylation). In all eukaryotes, certain snoRNAs (e.g., U3) are transcribed from classical promoters. In vertebrates, the majority are encoded in introns of protein-coding genes, and are released by exonucleolytic cleavage of linearized intron lariats. In contrast, in maize and yeast, nonintronic snoRNA gene clusters are transcribed as polycistronic pre-snoRNA transcripts from which individual snoRNAs are processed. In this article, 43 clusters of snoRNA genes, an intronic snoRNA, and 10 single genes have been identified by cloning and by computer searches, giving a total of 136 snoRNA gene copies of 71 different snoRNA genes. Of these, 31 represent snoRNA genes novel to plants. A cluster of four U14 snoRNA genes and two clusters containing five different snoRNA genes (U31, snoR4, U33, U51, and snoR5) from Arabidopsis have been isolated and characterized. Of these genes, snoR4 is a novel box C/D snoRNA that has the potential to base pair with the 3' end of 5.8S rRNA and snoR5 is a box H/ACA snoRNA gene. In addition, 42 putative sites of 2'-O-ribose methylation in plant 5.8S, 18S, and 25S rRNAs have been mapped by primer extension analysis, including eight sites novel to plant rRNAs. The results clearly show that, in plants, the most common gene organization is polycistronic and that over a third of predicted and mapped methylation sites are novel to plant rRNAs. The variation in this organization among gene clusters highlights mechanisms of snoRNA evolution. PMID- 11780638 TI - The snoRNA domain of vertebrate telomerase RNA functions to localize the RNA within the nucleus. AB - Telomerase RNA is an essential component of the ribonucleoprotein enzyme involved in telomere length maintenance, a process implicated in cellular senescence and cancer. Vertebrate telomerase RNAs contain a box H/ACA snoRNA motif that is not required for telomerase activity in vitro but is essential in vivo. Using the Xenopus oocyte system, we have found that the box H/ACA motif functions in the subcellular localization of telomerase RNA. We have characterized the transport and biogenesis of telomerase RNA by injecting labeled wild-type and variant RNAs into Xenopus oocytes and assaying nucleocytoplasmic distribution, intranuclear localization, modification, and protein binding. Although yeast telomerase RNA shares characteristics of spliceosomal snRNAs, we show that human telomerase RNA is not associated with Sm proteins or efficiently imported into the nucleus. In contrast, the transport properties of vertebrate telomerase RNA resemble those of snoRNAs; telomerase RNA is retained in the nucleus and targeted to nucleoli. Furthermore, both nuclear retention and nucleolar localization depend on the box H/ACA motif. Our findings suggest that the H/ACA motif confers functional localization of vertebrate telomerase RNAs to the nucleus, the compartment where telomeres are synthesized. We have also found that telomerase RNA localizes to Cajal bodies, intranuclear structures where it is thought that assembly of various cellular RNPs takes place. Our results identify the Cajal body as a potential site of telomerase RNP biogenesis. PMID- 11780639 TI - Genetic interactions between the 5' and 3' splice site consensus sequences and U6 snRNA during the second catalytic step of pre-mRNA splicing. AB - The YAG/ consensus sequence at the 3' end of introns (the slash indicates the location of the 3' splice site) is essential for catalysis of the second step of pre-mRNA splicing. Little is known about the interactions formed by these three nucleotides in the spliceosome. Although previous observations have suggested that the G of the YAG/ interacts with the first nucleotide of the /GUA consensus sequence at the 5' end of the intron, additional interactions have not been identified. Here we report several striking genetic interactions between A+3 of the 5' /GUA with Y-3 of the 3' YAG/ and G50 of the highly conserved ACAGAG motif in U6 snRNA. Two mutations in U6 G50 of the ACAGAG can weakly suppress two mutations in A+3 of the 5' /GUA. This suppression is significantly enhanced upon the inclusion of a specific mutation Y-3 in the 3' YAG/. RNA analysis confirmed that the severe splicing defect observed in A+3 and Y-3 double mutants can be rescued to near wild-type levels by the mutations in U6 G50. The contributions of each mutation to the genetic interaction and the strong position specificity of suppression, combined with previous findings, support a model in which the 5' /GUA and the GAG of U6 function in binding the 3' YAG/ during the second catalytic step. PMID- 11780640 TI - PUM2, a novel murine puf protein, and its consensus RNA-binding site. AB - Members of the Puf family of RNA-binding proteins from Drosophila, Caenorhabditis elegans, and Dictyostelium are known to function as translational repressors. To identify mammalian proteins that might regulate posttranscriptional gene expression, we have characterized a novel murine Puf protein, PUM2. Pum2 transcripts were expressed in all murine tissues examined, suggesting the gene influences processes common to many cell types. Like all Puf family members, PUM2 contains a C-terminal RNA-binding domain related to the Drosophila Pumilio homology domain (PUM-HD). Two features found in the amino-terminus of PUM2, regions rich in serine and glutamine/alanine-rich regions, were also identified in most Puf family members. RNA sequences capable of binding with high affinity (6.5 nM) to a 48-kDa recombinant protein containing the PUM2 PUM-HD were isolated by using an iterative amplification-selection protocol (SELEX). The consensus sequence [UGUANAUARNNNNBBBBSCCS] of the PUM2 binding element (PBE) is related to, but distinct from, the 3' end of the Drosophila Nanos response element. The characterization of PUM2 and potential RNA-binding site will assist efforts to assess the extent and mechanism by which mammalian genes are regulated at a posttranscriptional level. PMID- 11780641 TI - Concurrent molecular recognition of the amino acid and tRNA by a ribozyme. AB - We have recently reported an in vitro-evolved precursor tRNA (pre-tRNA) that is able to catalyze aminoacylation on its own 3'-hydroxyl group. This catalytic pre tRNA is susceptible to RNase P RNA, generating the 5'-leader ribozyme and mature tRNA. The 5'-leader ribozyme is also capable of aminoacylating the tRNA in trans, thus acting as an aminoacyl-tRNA synthetase-like ribozyme (ARS-like ribozyme). Here we report its structural characterization that reveals the essential catalytic core. The ribozyme consists of three stem-loops connected by two junction regions. The chemical probing analyses show that a U-rich region (U59 U62 in J2a/3 and U67-U68 in L3) of the ribozyme is responsible for the recognition of the phenylalanine substrate. Moreover, a GGU-motif (G70-U72) of the ribozyme, adjacent to the U-rich region, forms base pairs with the tRNA 3' terminus. Our demonstration shows that simple RNA motifs can recognize both the amino acid and tRNA simultaneously, thus aminoacylating the 3' terminus of tRNA in trans. PMID- 11780642 TI - Elongation factor G-induced structural change in helix 34 of 16S rRNA related to translocation on the ribosome. AB - During the translocation step of the elongation cycle, two tRNAs together with the mRNA move synchronously and rapidly on the ribosome. The movement is catalyzed by the binding of elongation factor G (EF-G) and driven by GTP hydrolysis. Here we study structural changes of the ribosome related to EF-G binding and translocation by monitoring the accessibility of ribosomal RNA (rRNA) for chemical modification by dimethyl sulfate or cleavage by hydroxyl radicals generated by Fe(II)-EDTA. In the state of the ribosome that is formed upon binding of EF-G but before the movement of the tRNAs takes place, residues 1054,1196, and 1201 in helix 34 in 16S rRNA are strongly protected. The protections depend on EF-G binding, but do not require GTP hydrolysis, and are lost upon translocation. Mutants of EF-G, which are active in ribosome binding and GTP hydrolysis but impaired in translocation, do not bring about the protections. According to cryo-electron microscopy (Stark et al., Cell, 2000, 100:301-309), there is no contact of EF-G with the protected residues of helix 34 in the pretranslocation state, suggesting that the observed protections are due to an induced conformational change. Thus, the present results indicate that EF-G binding to the pretranslocation ribosome induces a structural change of the head of the 30S subunit that is essential for subsequent tRNA-mRNA movement in translocation. PMID- 11780643 TI - Questioning CDC's "select agent" criteria. PMID- 11780644 TI - HHMI's attention to Wiley's lab staff. PMID- 11780645 TI - A unified definition of biosecurity. PMID- 11780646 TI - Graduate student unions. PMID- 11780647 TI - Successes of newborn screening programs. PMID- 11780648 TI - Invited commentary. Uveal melanoma: implications of tumor doubling time. PMID- 11780649 TI - Association between nasal methicillin-resistant Staphylococcus aureus carriage and infection in liver transplant recipients. PMID- 11780650 TI - Expanding the boundaries: enhancing dentistry's contribution to overall health and well-being of children. AB - The Surgeon General's Report, Oral Health in America, is the first comprehensive assessment of oral, dental, and craniofacial health in the history of our nation. The intent of this report is to alert all Americans to the full meaning of oral health and its importance to general health and well-being across the life span. Moreover, the report has been released at a time of enormous changes in human history as well as opportunities. The convergence of public health policies, "quality of life" expectations, global informatics, a new century of biotechnology, the advent of nanotechnology, the completion of the human genome project, changes in the management of health care, and the acknowledgment of enormous health disparities heralds a call to action. These changes affect children and their caregivers and the elderly. They also affect the social, economic, and health issues associated with special patients, including those with developmental disabilities. This paper highlights dentistry's future and how oral health is broadening the impact on patient and community health and dental practice, with a focus on children's oral health. The paper provides recommendations and suggests a call to action. PMID- 11780651 TI - A revolution in biomedical assessment: the development of salivary diagnostics. AB - Since the early 1900s, saliva has proven to be a noninvasive medium from which to measure a wide range of hormones, pharmaceuticals, and antibodies. It has also proven to be a convenient source of host and microbial DNA. As we enter the era of genomic medicine, increasing use of salivary diagnostics will help catalyze a shift from disease diagnosis to health surveillance. However, with the advances in this technology comes the additional obligation to ensure the privacy and rights of patients. PMID- 11780652 TI - Replacing and renewing: synthetic materials, biomimetics, and tissue engineering in implant dentistry. AB - Hundreds of thousands of implantations are performed each year in dental clinical practice. Dental implants are a small fraction of the total number of synthetic materials implanted into the human body in all fields of medicine. Basically, these millions of implants going into humans function adequately. But longevity and complications still are significant issues and provide opportunities for the creation of improved devices. This manuscript briefly reviews the history of dental implant devices and the concepts surrounding the word "biocompatibility." It then contrasts the foreign body reaction with normal healing. Finally, the article describes how ideas gleaned from the study of normal wound healing can be applied to improved dental implants. In a concluding section, three scenarios for dental implants twenty years from now are envisioned. PMID- 11780653 TI - Making patients safe and comfortable for a lifetime of dentistry: frontiers in office-based sedation. AB - Conscious sedation administered in the office setting is one important method for helping people obtain necessary dental care. Patients who may benefit from sedation include the dentally fearful, young children, the behaviorally or medically challenged, and individuals who are undergoing invasive procedures or have problems with gagging or local anesthesia. In-office sedation is effective in reducing apprehension and can improve patient behavior without adversely affecting the patient's physiological status. Mortality and serious morbidity are exceedingly rare in modern practice. Although behavioral strategies are clearly more cost-effective for the patient receiving routine dental care, in-office sedation is usually the least expensive alternative for patients requiring pharmacologic management. Future advances in conscious sedation may include agents and techniques currently thought to be dangerous for nongeneral anesthesia trained dentists because of their ability to produce rapid changes in anesthetic depth. However, delivery devices such as infusion pumps for drugs like propofol, when coupled with computers to help regulate the infusion rate and monitor the sedative effect, may provide the necessary control for safe administration of propofol and similar drugs by these individuals. A final approach to drug delivery may involve patient-controlled sedation in which the patient self infuses small boluses incrementally until the desired effect is achieved. PMID- 11780654 TI - Long-term management of the fearful adult patient using behavior modification and other modalities. AB - This paper reviews reports on the treatment of fearful adult dental patients with special emphasis on behavioral and cognitive methods and long-term followup. A number of such treatment methods are available that can be used by dentists for the alleviation of fear and anxiety in their patients. At an "intuitive" level, many dentists probably use these methods frequently as a comprehensive part of everyday praxis. Considering the high number of fearful individuals visiting dentists regularly, a better knowledge of such methods would improve dental care for the majority of these patients. It would also help prevent aggravation of fears among individuals at risk. However, despite the success of treatment methods performed by specially trained dentists, it seems reasonable that there should be limits to what can be expected of a dentist in terms of psychological, diagnostic, and therapeutic competence. Dental phobia may constitute a complex psychological and odontological problem with far-reaching consequences for a relatively large proportion of fearful individuals. It therefore seems likely that optimal care of such patients can best be achieved by cross-disciplinary efforts involving both dentists and psychologists. PMID- 11780655 TI - Guiding and managing the child dental patient: a fresh look at old pedagogy. AB - Society's approach to children during the past half-century has changed dramatically, and a transformation of medical and hospital pediatric care has followed. Dentistry has been slower to incorporate sound, child-friendly approaches to care. Nonetheless, much has changed in dental practice pertaining to children. The regular involvement of parents in the surgical/therapeutic suite is one such change. Expanded communication to ensure informed consent for treatment as well as consent for type of management approach to children is the standard of care. Since sedation policies are becoming more complex, enhancing the skills of all dentists and staff members in the best methods of nonpharmacological child management will be essential in the next decades. Biobehavioral methods will gain prominence, along with better communication skills of the dental team. These changes will occur only if more time and resources are positioned to teach dental students, dentists, and staff the necessary skills. Emphasis must be placed on early, timely intervention; parental involvement; effective communication; cultural competence; and the "medical/dental home" concept as methods to reduce negative dental attitudes and behaviors of children. PMID- 11780656 TI - Pain and the neuromatrix in the brain. AB - The neuromatrix theory of pain proposes that pain is a multidimensional experience produced by characteristic "neurosignature" patterns of nerve impulses generated by a widely distributed neural network-the "body-self neuromatrix"-in the brain. These neurosignature patterns may be triggered by sensory inputs, but they may also be generated independently of them. Acute pains evoked by brief noxious inputs have been meticulously investigated by neuroscientists, and their sensory transmission mechanisms are generally well understood. In contrast, chronic pain syndromes, which are often characterized by severe pain associated with little or no discernible injury or pathology, remain a mystery. Furthermore, chronic psychological or physical stress is often associated with chronic pain, but the relationship is poorly understood. The neuromatrix theory of pain provides a new conceptual framework to examine these problems. It proposes that the output patterns of the body-self neuromatrix activate perceptual, homeostatic, and behavioral programs after injury, pathology, or chronic stress. Pain, then, is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain. Its output pattern is determined by multiple influences, of which the somatic sensory input is only a part, that converge on the neuromatrix. PMID- 11780657 TI - Chronic orofacial pain: is the puzzle unraveling? AB - Conditions involving chronic orofacial pain represent a major health problem, and patients with persistent pain are difficult to manage successfully. These conditions are often comorbid with additional health issues such as sleep disturbances, cardiovascular, gastrointestinal and reproductive system complaints, weight loss or weight gain, swelling, numbness, sweating and flushing, and concerns regarding loss of libido, drive, attention, and memory. Neuroendocrine and autonomic pain-stress responsivity and the consequences of pain for sensory, motor, immune and reproductive functions, and mood seem to account for the broad range of comorbid complaints. Susceptibility to a particular response appears to explain intra-individual differences in disease expression. Understanding of these regulatory, mostly adaptive processes will support novel treatments to manage many troublesome comorbid complaints for which current approaches are unsatisfactory. PMID- 11780658 TI - Pharmacologic advances in orofacial pain: from molecules to medicine. AB - The management of chronic orofacial pain often follows a pattern of claims of efficacy based on clinical observations superseded by equivocal findings of effectiveness or belated recognition of toxicity. While therapeutic innovation spurred by genomics and proteomics is likely to result in new drugs for pain, inflammation, and neuropathic pain, the process of drug development and approval takes five to ten years and is often unsuccessful. Therapeutic strategies for improving treatment for chronic orofacial pain are proposed, but recognition of impediments to changing clinical practices suggest the need for interim measures. Greater understanding of the molecular and genetic events that contribute to pain chronicity and interindividual variations in pain responsiveness may eventually result in individualized molecular pain medicine to prevent and treat chronic orofacial pain. PMID- 11780659 TI - Dental work force strategies during a period of change and uncertainty. AB - Both supply and demand influence the ability of the dental work force to adequately and efficiently provide dental care to a U.S. population growing in size and diversity. Major changes are occurring on both sides of the dental care market. Among factors shaping the demand for dental care are changing disease patterns, shifting population demographics, the extent and features of third party payment, and growth of the economy and the population. The capacity of the dental work force to provide care is influenced by enhancements of productivity and numbers of dental health personnel, as well as their demographic and practice characteristics. The full impact of these changes is difficult to predict. The dentist-to-population ratio does not reflect all the factors that must be considered to develop an effective dental work force policy. Nationally, the dental work force is likely to be adequate for the next several years, but regional work force imbalances appear to exist and may get worse. Against this backdrop of change and uncertainty, future dental work force strategies should strive for short-term responsiveness while avoiding long-term inflexibility. Trends in the work force must be continually monitored. Thorough analysis is required, and action should be taken when necessary. PMID- 11780660 TI - The dentist as biobehavioral clinician. AB - At the core of all clinical dental practice is the interpersonal interaction between dentist and patient. An expansion of the dentist's responsibility in the unique dentist-patient relationship is suggested. Such an expanded role encourages dentists to engage the emotional and behavioral health of dental patients who are appearing in dental offices for treatment of orofacial diseases and other conditions. The term "biobehavioral clinician" is used to refer to this broadened role for the dentist. It is suggested that such a biobehaviorally oriented dentist will be a powerful ally on behalf of the health of patients, attending to more dimensions of the patient's presentation and management than the diagnosis and treatment of oral pathobiology. It seems entirely appropriate that dentists have such a role in its future, engaging as they do millions and millions of Americans on a regular basis and a productive and collaborative dentist-patient relationship is already an accomplished fact for most dentists with most of their patients across all stages of the life span. The benefit to patients' overall health and well-being could be tremendous and would add an enriching and personally rewarding dimension to being a dentist. PMID- 11780661 TI - The role of dentists in dentistry. AB - The extent to which dentists influence the outcomes of dental care, compared to the effects of dental technology or patient variation, has not been well studied. A review of the literature on the personality and value structures of dentists and dental students reveals general trends involving preferences of concrete, utilitarian, unambiguous, and conventional situations that are classified and judged in terms of their potential for dentists' power and control and for relationships of helping others but avoiding mutual dependency. These findings are summarized in a hypothesis that dentists seek situations where they can exercise control and establish paternalistic relationships with others. The evidence about career satisfaction of dentists is difficult to interpret. Between 20 percent and 50 percent of dentists report that they would not choose to enter the profession again if given a chance. Yet the number leaving the profession voluntarily is less than the number of career changers in the general population by a factor of about 1 to 15. Career satisfaction of practitioners can be partially predicted from an understanding of dentists' personality and values. Factors such as uncooperative patients, incompetent staff, and government and insurance intrusions are major dissatisfiers; they threaten dentists' core need for control. Factors such as quality of work, which is under the control of dentists, are major satisfiers. The personalities and values of dentists and the expression of these in professional norms may function to limit our understanding of dentistry. Based on this analysis, eight predictions are offered about the profession. PMID- 11780662 TI - Dietary supplements reduce risk of vision loss from age-related macular degeneration. PMID- 11780663 TI - Use of a Shack-Hartmann aberrometer to assess the optical outcome of corneal transplantation in a keratoconic eye. AB - We report the optical outcome of corneal transplantation treatment on a keratoconic eye as measured with a Shack-Hartmann aberrometer, and we compare the results with the recovery of visual acuity after surgery. Before surgery, the naked keratoconic eye exhibited extremely large aberrations that could not be measured unless the patient wore a rigid gas-permeable contact lens. With the lens, the computed point-spread function of the eye was large and multimodal, and simulated retinal images confirmed the patient's subjective report of multiple, overlapping images. After full recovery from surgery, aberrations of the corrected eye were much smaller compared with the presurgical eye, which implied a more compact point-spread function and clearer retinal images. These optical changes were mirrored by an improvement in uncorrected visual acuity from 1.3 logarithm of the minimum angle of resolution (logMAR) before surgery to 0 logMAR with spectacle correction after full recovery. We conclude that the Shack Hartmann aberrometer provides an objective, quantitative assessment of the optical outcome of penetrating keratoplasty that allows the clinician to measure retinal image quality objectively and to accurately simulate the complex visual distortions associated with keratoconus. PMID- 11780664 TI - On-eye evaluation of optical performance of rigid and soft contact lenses. AB - A Shack-Hartmann aberrometer was used to assess the optical performances of eyes corrected with rigid or soft contact lenses compared with spectacles. Metrics of optical quality derived from the measured wave aberrations were consistent with the subjective rating of visual clarity by subjects. Optical aberration analysis illustrated the differences in aberration structures of eyes wearing different optical corrections. For our subjects, correction with a rigid gas-permeable lens yielded significantly better optical quality than did the soft contact lens or spectacle lens. This was due to a reduction in the eye's asymmetric (odd-order) aberrations and a reduction in the amount of the eye's positive spherical aberration. These observations can be explained by theoretical calculations of the aberrations of the eye plus lens optical system. We conclude that aberrometry provides a better understanding of the optical effects of contact lenses in situ and could be useful for optimizing future designs of contact lenses. PMID- 11780665 TI - Corneal and refractive error astigmatism in Singaporean schoolchildren: a vector based Javal's rule. AB - BACKGROUND: Traditional approaches to Javal's rule do not use data from subjects with oblique astigmatism and have not been used to make predictions about subjects with oblique astigmatism. Vector approaches to analyzing refractive error can circumvent these problems. METHODS: Subjects were 993 Singaporean schoolchildren. We performed linear regression of refractive error astigmatism on corneal astigmatism, using J0 vectors to describe with-the-rule and against-the rule astigmatism and J45 vectors to describe oblique astigmatism. RESULTS: We obtained the following statistically significant regression relationships: RJ0 = 0.931 x CJ0 - 0.276 and RJ45 = 0.638 x CJ45 + 0.010, where R and C denote refractive error astigmatism and corneal astigmatism, respectively. CONCLUSION: Our vector-based Javal's rule gives closer predictions of refractive astigmatism than the original Javal's rule and the simplified Javal's rule and can be applied in cases of corneal oblique astigmatism. PMID- 11780666 TI - Magnification, blur, and ray state at the retina for the general eye with and without a general optical instrument in front of it: 1. Distant objects. AB - PURPOSE: To derive general equations that characterize rays, magnification, and blur at the retina in the case of distant object points for a naked eye and for an eye looking through an arbitrary optical instrument. The eye and optical instrument may be astigmatic and noncoaxial. METHOD: The derivation is based on linear optics and makes use of the concept of the augmented ray transference of an optical system. Because the transference completely characterizes the linear optics, the analysis can claim completeness. RESULTS: Equations are presented for position and direction of rays at the retina from distant object points. They lead naturally to the definition of six properties that characterize blur, shape, size, orientation, and position of images of distant objects viewed by the naked eye and by the eye looking through an instrument. By way of example, the general equations are applied to the simple examples of a thin contact lens and a thin spectacle lens in particular. CONCLUSION: The analysis provides a framework, complete as far as linear optics is concerned, for the analysis of light arriving at the retina through any instrument from a distant point. In so doing, it unifies and generalizes concepts like blur and spectacle magnification, which, in the past, have been treated separately. PMID- 11780667 TI - Magnification, blur, and ray state at the retina for the general eye with and without a general optical instrument in front of it: 2. Near objects. AB - PURPOSE: To derive general equations that characterize rays, magnification, and blur at the retina in the case of near object points for the naked eye and for the eye in combination with a general optical instrument. METHOD: The paper draws on results obtained via linear optics in an accompanying paper. RESULTS: Equations are presented that completely characterize the state of rays at the retina from objects at any distance. They allow quantification of blur, size, shape, orientation, and magnification at the retina. CONCLUSION: The analysis provides a framework, complete in linear optics, for the analysis of light arriving at the retina of a general eye through any instrument from any object point. PMID- 11780668 TI - Perceived segment misalignment in anisometropic spectacle corrections. AB - In anisometropic bifocals or trifocals, the magnification difference between left and right lenses will often distort the perceived alignment of the segments. The effect is most noticeable with the segment tops in bifocals or the dividing line between near and intermediate fields in trifocals. The perceived misalignment occurs because off-axis image points are displaced unequal amounts in right and left fields, which forces the lines of sight to diverge to achieve fusion. Hence, the left and right segments will appear at different levels even though they may be perfectly aligned in the spectacle lenses. This article explains why the perceived misalignment occurs, how it can be determined and quantified, and how it can be reduced or eliminated. PMID- 11780669 TI - Word acuity threshold as a function of contrast and retinal eccentricity. AB - BACKGROUND: We determined word acuity thresholds as a function of contrast and retinal eccentricity to determine the rate of threshold alteration in the normal retinal periphery. METHODS: Subjects identified words presented foveally (0 degrees eccentricity) or above the point of fixation at retinal eccentricities of 0.5, 1, 2, 3, 6, and 8 degrees for three contrast levels of 10, 45, and 85%. A descending method of limits was used to determine thresholds for random four letter words flashed for 90 ms at the different retinal eccentricities. RESULTS: For high-contrast letters, word acuity displayed threshold elevation in the periphery similar to previous reports and similar threshold elevation to those reported for vernier acuity. Lower contrast levels displayed different threshold change as a function of eccentricity, approaching levels reported for grating acuity. When comparing the relative elevation of word acuity thresholds for the different contrast levels (85 vs. 45% and 85 vs. 10%), both comparisons showed that the most rapid decline in word acuity threshold occurs within 2 degrees of the fovea. CONCLUSIONS: The peripheral retina displays a reduction in word acuity threshold that is dependent on letter contrast and shows a change similar to those reported for higher cortical functions such as vernier thresholds. The greatest word threshold elevation occurs within the central 2 degrees of the fovea. PMID- 11780670 TI - Hypertension: a turning point in the history of medicine...and mankind. PMID- 11780671 TI - Recognizing and responding to an attack with a biological weapon. PMID- 11780672 TI - Delayed diagnosis of intracranial aneurysms. PMID- 11780673 TI - Hypertension 2001: pearls for the clinician. AB - Diuretics and beta-blockers are presently recommended as first-line therapy for the treatment of uncomplicated hypertension. JNC VII will probably consider ACE inhibitors worthy of this recommendation. In those at high risk for CHD or CHF, the initial use of an alpha-blocker or calcium antagonist will be recommended with caution. In those with systolic hypertension, who remain at increased risk of stroke, the initial use of CCB therapy continues to be supported by trial based evidence. A diuretic, based on outcome-based trials, should be included in most regimens to lower the risk of ischemic stroke. Since most patients will require two or more drugs to control their blood pressure, the initial agent chosen will assume less importance for the practicing physician. PMID- 11780674 TI - Renovascular hypertension: can we identify a population at high risk? AB - Renovascular hypertension is a common cause of secondary hypertension. However, diagnostic tests are limited by lack of sensitivity and specificity, cost, or invasiveness. Selecting patients with hypertension for evaluation of renal artery stenosis can be challenging. This review focuses on the sensitivity and specificity of commonly used screening tests for renal artery stenosis and on the clinical variables that are most likely to distinguish patients with renal artery stenosis from patients with other causes of their hypertension. This approach allows for the rational screening of patients at high and moderate risk for renal artery disease. PMID- 11780675 TI - Hypertension. Medication update. PMID- 11780676 TI - Antihypertensive medications. PMID- 11780677 TI - Hypertension. Annotated bibliography. PMID- 11780678 TI - Coding according to local medical review policy. PMID- 11780679 TI - Delayed diagnosis of intracranial aneurysms: confounding factors in clinical presentation and the influence of misdiagnosis on outcome. AB - The initial presentation of intracranial aneurysm can be missed in routine clinical practice. An underlying aneurysm may have a subtle presentation that warrants definitive diagnostic procedures. A retrospective review of 270 patients with aneurysms at our institution revealed 40 patients (14.8%) with a significant delay in diagnosis before definitive treatment. The delay due to missed diagnosis varied from 2 days to a few months. In retrospect, 58% had a Hunt and Hess grade I clinical presentation at readmission. Clinical status was rated as grade 0-I in the majority of patients (65%), grade II in 20%, and grade III in 12.5%. One patient had grade IV status. These grades are significantly different from the initial grade at which each of the patients first sought medical attention. The second admission significantly affected the outcome. A delay in diagnosis of aneurysmal subarachnoid hemorrhage resulting in poor clinical grade influenced neurologic outcome significantly. PMID- 11780680 TI - Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. AB - BACKGROUND: Increasing numbers of the adult population are using alternative or complementary health resources in the treatment of chronic medical conditions. Systemic hypertension affects more than 50 million adults and is one of the most common risk factors for cardiovascular morbidity and mortality. This study evaluates the antihypertensive effectiveness of oral coenzyme Q10 (CoQ), an over the-counter nutritional supplement, in a cohort of 46 men and 37 women with isolated systolic hypertension. METHODS: We conducted a 12-week randomized, double-blind, placebo-controlled trial with twice daily administration of 60 mg of oral CoQ and determination of plasma CoQ levels before and after the 12 weeks of treatment. RESULTS: The mean reduction in systolic blood pressure of the CoQ treated group was 17.8 +/- 7.3 mm Hg (mean +/- SEM). None of the patients exhibited orthostatic blood pressure changes. CONCLUSIONS: Our results suggest CoQ may be safely offered to hypertensive patients as an alternative treatment option. PMID- 11780681 TI - Rapidly progressive visual loss caused by a sellar arachnoid cyst: reversal with transsphenoidal microsurgery. AB - Rapidly progressive vision loss is an uncommon presentation of a parasellar lesion. This report describes a patient with a sellar arachnoid cyst with suprasellar extension in whom rapidly progressive loss of vision was reversed by transsphenoidal microsurgical decompression and cyst fenestration. The differential diagnosis of cystic lesions of the sella and parasellar area is discussed, with emphasis on the importance of early intervention for vision recovery. PMID- 11780682 TI - Antinuclear antibody-negative, drug-induced lupus caused by lisinopril. AB - The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL. PMID- 11780683 TI - Intravenous lidocaine in the treatment of hiccup. AB - The word "hiccup" refers to an involuntary, spasmodic contraction of the diaphragm that is followed by the abrupt closure of the glottis to produce the characteristic sound. Among the many documented causes of this occurrence are those due to neurogenic dysfunction. In the past few decades, lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms, including seizures, chronic pain, and arrhythmias. We describe a postsurgical patient in whom two successive intravenous infusions of lidocaine, 1.5 mg/kg followed the next day by 0.75 mg/kg, terminated his hiccup twice, whereas multiple other treatments failed to alleviate the problem. Various causes of this phenomenon are discussed, as well as a possible mechanism for the successful treatment. PMID- 11780684 TI - Reactions of Veterans Administration psychiatric patients to the September 2001 terrorist attacks. PMID- 11780685 TI - Central serous retinopathy following long-duration laser pointer exposure. PMID- 11780686 TI - Seastroke. PMID- 11780687 TI - Liddle syndrome: genetics and mechanisms of Na+ channel defects. AB - Our current understanding of Na+ transport defects has been greatly expanded over the last several years and has provided new insights into unusual clinical syndromes resulting from mutations of specific ion transporters. These genetic disorders affect Na+ balance, with both Na+ retaining and Na+ wasting conditions being the consequence. A major focus of these studies has been the epithelial sodium channel (ENaC), which can be directly affected by mutations (eg, Liddle syndrome, autosomal recessive pseudohypoaldosteronism, type I) or by changes in the response to (autosomal recessive pseudohypoaldosteronism, type I), or production of mineralocorticoids (apparent mineralocorticoid excess syndrome, glucocorticoid-remediable aldosteronism). As a result, we now have clearly defined syndromes in which ENaC activity is "dysregulated" with subsequent development of disorders of systemic blood pressure that can be attributed to a primary renal mechanisms. The focus of the current review is on Liddle syndrome ("pseudoaldosteronism"). PMID- 11780688 TI - 11beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. AB - Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may result in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11beta-hydroxysteroid dehydrogenase (11-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11-HSD. The liver or 11-HSD1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney or 11-HSD2 isozyme has high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, the in vitro enzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisone to cortisol metabolites in the urine, with age of diagnosis, and with birth weight. This suggests that the biochemical and clinical phenotype of AME is largely determined by genotype. PMID- 11780689 TI - Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes. AB - Inherited hypokalemic metabolic alkalosis, or Bartter syndrome, comprises several closely related disorders of renal tubular electrolyte transport. Recent advances in the field of molecular genetics have demonstrated that there are four genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Neonatal Bartter syndrome affects neonates and is characterized by polyhydramnios, premature delivery, severe electrolyte derangements, growth retardation, and hypercalciuria leading to nephrocalcinosis. It may be caused by a mutation in the gene encoding the Na-K-2Cl cotransporter (NKCC2) or the outwardly rectifying potassium channel (ROMK), a regulator of NKCC2. Classic Bartter syndrome is due to a mutation in the gene encoding the chloride channel (CLCNKB), also a regulator of NKCC2, and typically presents in infancy or early childhood with failure to thrive. Nephrocalcinosis is typically absent despite hypercalciuria. The hypocalciuric, hypomagnesemic variant of Bartter syndrome (Gitelman syndrome), presents in early adulthood with predominantly musculoskeletal symptoms and is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT). Even though our understanding of these disorders has been greatly advanced by these discoveries, the pathophysiology remains to be completely defined. Genotype-phenotype correlations among the four disorders are quite variable and continue to be studied. A comprehensive review of Bartter and Gitelman syndromes will be provided here. PMID- 11780690 TI - The calciuric response to dietary salt of Dahl salt-sensitive and salt-resistant female rats. AB - BACKGROUND: We have shown previously that the calciuric response to salt does not differ in Dahl salt-sensitive (S) and salt-resistant (R) male rats. Clinical studies with women, however, suggest an effect of salt sensitivity on the calciuric response to salt. The objective of this study was to determine whether there is an effect of salt sensitivity on the calciuric response to salt of female S and R rats. METHOD: Dahl S and R female rats were fed high- (8%) or low- (0.3%) salt diets for 3 weeks. The rats were placed in metabolic cages for 24 hour urine collection at baseline and weekly (for sodium and calcium determination). RESULTS: Blood pressure of female S rats was 177+/-3.0 mm Hg at week 3 of high salt intake compared with 96+/-1 mm Hg for female R rats. Female S rats excreted significantly more calcium than female R rats at baseline (P < 0.001), when fed a nonpurified diet, and during high salt intake (P = 0.004). Salt sensitivity significantly increased calcium excretion, water intake, and urine output when rats were fed a high-salt diet. Calcium excretion, water intake, and urine output of female S rats were time-dependent during high salt intake. Plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations were markedly lower in female S rats fed a high-salt diet, but not in female R rats. Plasma parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not significantly differ between female S and R rats, but plasma concentrations of these two hormones at week 3 were significantly higher in S rats fed a high salt diet compared with S rats fed a low-salt diet. CONCLUSIONS: Our data indicate that the calciuric response to salt is greater in female S compared with female R rats, thus supporting findings on the effect of salt sensitivity reported in several clinical studies with women. The greater calciuric response to salt of female S rats compared with female R rats, which was not seen in a previous study when male S rats were compared to male R rats, suggest a gender difference in the calciuric response to salt. PMID- 11780692 TI - Carboxyhemoglobin levels in patients with sickle-cell anemia: relationship to hemolytic and vasoocclusive severity. AB - BACKGROUND: When carbon monoxide binds to hemoglobin, it increases the affinity of hemoglobin for oxygen and shifts the oxygen dissociation curve to the left. The resulting decrease in sickling tendency could have clinical benefit, and carbon monoxide has been suggested as a treatment for sickle-cell disease. Furthermore, in sickle-cell disease, as in other hemolytic diseases, endogenous carbon monoxide production is increased because of increased heme catabolism. METHODS: In the present study, we measured carboxyhemoglobin levels in sickle cell patients and compared them with estimates of the hemolytic and the vasoocclusive severity of the disease. RESULTS: Significant correlation was found between carboxyhemoglobin (HbCO) levels and hematocrit, reticulocyte count, unconjugated bilirubin level, and percentage of irreversibly sickled cells. However, there was no significant correlation between carboxyhemoglobin levels and measures of the vaso-occlusive severity of the disease. CONCLUSIONS: The correlations between HbCO levels and measures of hemolytic severity are best explained by the known relationship between hemoglobin catabolism and CO production. The lack of correlation with vaso-occlusive severity may be due to the complex changes involved and the difficulty of quantifying vasoocclusive severity. PMID- 11780691 TI - Feasibility and reliability of rapid diagnosis of myocardial infarction. AB - BACKGROUND: Prevailing hospital practice dictates a protracted phase of observation for patients with chest pain to establish or exclude the diagnosis of myocardial infarction. Early diagnosis of acute myocardial infarction may improve patient care and reduce both complications and hospital costs. A study was performed to investigate the feasibility of early diagnosis of myocardial infarction within the first 9 hours of the hospital stay. METHODS: The records of all patients admitted with chest pain within one calendar year were analyzed. The timing of creatine kinase-MB (CK-MB) quantification was determined with reference to the initial phlebotomy (time 0). An enzymatic diagnosis of myocardial infarction was assigned if any determination of CK-MB exceeded the upper limit of normal, and the diagnosis of each patient at or before 9 hours (early diagnosis) was compared to the ultimate diagnosis at 14 to 24 hours (final diagnosis) beyond initial assessment. RESULTS: Of the 528 included patients, 523 patients (99.1%) had identical early and final diagnostic outcomes; 5 patients (0.9%) had conflicting results. An early diagnosis of myocardial infarction was assigned to 195 of the 528 patients (36.9%). Of these, 190 achieved the diagnosis within 9 hours (sensitivity 97.4%). The negative predictive value was 98.5%. CONCLUSION: Standard CK-MB mass measurements within 9 hours of arrival provided an accurate clinical assessment in > 99% of the cases. The high sensitivity and negative predictive values suggest that early diagnosis of myocardial infarction is feasible and reliable. PMID- 11780693 TI - Teaching doctor-patient interviewing skills using an integrated learner and teacher-centered approach. AB - BACKGROUND AND OBJECTIVE: We describe an approach for the resolution of difficulties that some preclinical medical students appeared to have when acquiring patient interviewing skills. SETTING: Two medical schools in Israel. TYPE OF STUDY: Descriptive. OBSERVATIONS: Students' difficulties were related to the inconsistency between the patient-centered approach that was emphasized in the preclinical teaching programs and the disease-centered (biomedical) approach that was practiced on the wards. Others were confused by ambiguous vocabulary and by the multiplicity of rules that they had to remember. Still others appeared to resent attempts to teach them what they thought was elementary courtesy, to reject counterintuitive interviewing rules, and to be bored by the repetitive nature of the practice sessions. TEACHING INTERVENTION: We used an integrated learner- and teacher-centered approach, which is based on the premise that students learn more effectively when autonomous and self-motivated than when responding to instructions from others. Rather than the students being lectured, they were asked to identify the problems in doctor-patient communication and to propose solutions. We conducted live demonstrations of patient- and disease centered interviews and encouraged students to discuss the advantages and disadvantages of each of them. Lastly, we supervised students as they interviewed patients with increasingly difficult communication problems. CONCLUSIONS: The described approach is consistent with current theories of adult learning. It permits the instructor's input and also supports students' autonomy in identifying and resolving problems in patient interviewing and in choosing the balance between patient- and disease-centered interviewing styles according to the patient's needs. The feasibility of our approach is conditional on the availability of instructors who feel comfortable conducting group discussions, are familiar with the literature on doctor-patient relations, and are experienced enough to demonstrate different interviewing techniques using live patients. PMID- 11780694 TI - Deep venous thrombosis: a review of the pathophysiology, clinical features, and diagnostic modalities. PMID- 11780695 TI - A 66-year-old man with hepatosplenomegaly and pancytopenia. PMID- 11780696 TI - Alpha-fetoprotein-producing male breast cancer accompanied with hepatocellular carcinoma: assessment by lectin-affinity profile. AB - An autopsy case associated with both male breast cancer and hepatocellular carcinoma in which serum alpha-fetoprotein (AFP) was extremely elevated is described. The source of AFP production was investigated. In lectin-affinity chromatography of the patient's serum, concanavalin A (ConA) binding pattern was not consistent with that of hepatocellular carcinoma, and lens culinaris agglutinin A (LCA) affinity indicated a similar pattern to hepatocellular carcinoma. The immunohistochemistry staining for AFP revealed positive reactivity in breast cancer cells, but was negative in hepatocellular carcinoma cells. To the best of our knowledge, there have been no reports of breast cancer exhibiting immunohistochemically positive AFP in breast cancer cells. In the present case, ConA binding test was useful for identification of the source of AFP production. Furthermore, corresponding aggravation of breast cancer to the elevation of AFP suggested the possibility that AFP might enhance breast cancer growth. PMID- 11780698 TI - Maximizing radiation benefit in breast cancer. PMID- 11780697 TI - Tuberculous arthritis mimicking neoplasm in a hemodialysis patient. AB - Hemodialysis patients are known to develop the complication of extrapulmonary tuberculosis more frequently than the general population. Tuberculous arthritis is a rare form of extrapulmonary tuberculosis and is reported to occur in approximately 1% of cases in nonuremic patients. Only 3 cases in dialysis patients, who were not proven by a bacterial culture or had died before treatment, have been reported. We report herein a culture-proven case of tuberculous arthritis developing at the sternoclavicular joint, which initially mimicked an apparent neoplasm in a hemodialysis patient. A favorable outcome was obtained after antituberculous therapy. Tuberculosis must be considered one of the most significant diagnoses in hemodialysis patients who present with a tumor like lesion. PMID- 11780699 TI - Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung cancer. AB - The role of adjuvant therapy following complete resection of node-positive (stage II/IIIA) non-small-cell lung cancer remains controversial. Five-year survival rates in pathologic stage II disease range from 30% to 50% and in resected stage IIIA disease from 10% to 30%. The majority of recurrences following surgery are distant metastases. This two-part review, which will conclude in the January 2002 issue, analyzes the role of adjuvant therapy in this setting, using an evidence based approach and focusing primarily on randomized trials and meta-analyses. The key variables in evaluating these studies are elucidated, ranging from the extent of mediastinal, systemic, and "molecular" staging to the quality of the adjuvant treatments administered. Some of the potential flaws inherent in meta-analyses are reviewed. To date, there is no convincing evidence that any therapy consistently improves survival in the adjuvant setting. Postoperative radiotherapy has been associated with a significant improvement in local control, particularly in patients with pathologic N2 disease. Chemotherapy should be offered to patients in appropriate clinical trials, and active phase III trials are reviewed. Future strategies include novel chemotherapy, methods to reduce toxicity, the emerging role of neoadjuvant therapy, and the promise of new biologic agents. PMID- 11780700 TI - Docetaxel combination produces 2-year survival advantage in NSCLC patients. PMID- 11780701 TI - Geriatric syndromes and assessment in older cancer patients. AB - Older individuals are at risk for adverse events in all settings where cancer is treated. Common geriatric syndromes can complicate cancer therapy, and thus, increase patient morbidity and the costs of care. Furthermore, cancer treatment can worsen geriatric syndromes. It is often difficult to determine whether declining health is a result of cancer treatment or the patient's underlying disease. Baseline assessment of multiple factors may facilitate detection of a decline in the patient's health status, which may be remediable. Geriatric syndromes may substantially affect quality of life and are also important in the prognosis and outcome of cancer therapy. This article reviews the assessment of cognitive syndromes (dementia and delirium), vision and hearing impairment, gait and balance difficulties, malnutrition, incontinence, depression, osteoporosis, sleep disorders, environmental and social issues, and functional decline. Although there are many geriatric domains and many focused assessment tools, assessment does not need to be time-consuming. Streamlined assessment tools have been developed; they are brief, inexpensive, and easily administered, and they may be valuable to the oncologist. Staff such as nurses, social workers, or office personnel could perform these assessments and minimize the impact on the physician's time. PMID- 11780702 TI - Clinical trials referral resource. Current clinical trials of fenretinide. PMID- 11780703 TI - Modulation of dose intensity in aerodigestive tract cancers: strategies to reduce toxicity. AB - Advances in diagnostic and therapeutic radiology and a better understanding of cell biology are being applied in practical ways to modulate treatment morbidity. Conformal radiotherapy targets the cancer precisely and can be combined with new systemically administered radiosensitizers. The successes of conventional chemoradiation programs support continued study of newer ways to deliver systemic radiosensitizing chemotherapy. However, chemoradiation creates a narrower therapeutic window compared to irradiation alone and increased treatment intensity, even with conformal chemoradiation techniques, can potentially result in frequent complications, detrimental treatment delays, and decreased quality of life. Treatment schedules employing a "best tolerated time" modelfor systemic administration of radiosensitizing chemotherapy, based on the concept of chronotolerance, offer attractive ways to address the challenging problem of normal tissue toxicity associated with conformal chemoradiation. This approach may be beneficial in the elderly and those medically unfit to tolerate traditional dose-intense combined-modality schedules. Further evaluation of this concept is warranted, based on existing data. PMID- 11780704 TI - Classification of cancer pain syndromes. AB - Cancer patients experience pain in multiple sites and from several pathophysiologies of the symptom complex. The fluctuating nature of cancer pain intensity is a relevant clinical feature and depends on disease patterns and pain mechanisms. Breakthrough pain is defined as episodes of pain that "break through" the control of an otherwise effective analgesic therapy. Traditional ways of classifying pain in the cancer population include distinguishing pain associated with the treatments, the tumor, or unrelated to both and between chronic and acute pain. In focusing on the care of the cancer patient with pain, it is useful to be familiar with the characteristics of the typical syndrome found in association with different tumor types and anatomic locations. An understanding of the etiology of pain in relation to the cancer is useful in recognizing these complications and in treating them. This article reviews the methods presently applied to the classification of cancer pain and highlights the need for more research in this area. PMID- 11780705 TI - Web-based tailored nutrition education: results of a randomized controlled trial. AB - There is ample evidence that printed, computer-tailored nutrition education is a more effective tool for motivating people to change to healthier diets than general nutrition education. New technology is now providing more advanced ways of delivering tailored messages, e.g. via the World Wide Web (WWW). Before disseminating a tailored intervention via the web, it is important to investigate the potential of web-based tailored nutrition education. The present study investigated the immediate impact of web-based computer-tailored nutrition education on personal awareness and intentions related to intake of fat, fruit and vegetables. A randomized controlled trial, with a pre-test-post-test control group design was conducted. Significant differences in awareness and intention to change were found between the intervention and control group at post-test. The tailored intervention was appreciated better, was rated as more personally relevant, and had more subjective impact on opinion and intentions to change than the general nutrition information. Computer literacy had no effect on these ratings. The results indicate that interactive, web-based computer-tailored nutrition education can lead to changes in determinants of behavior. Future research should be aimed at longer-term (behavioral) effects and the practicability of distributing tailored interventions via the WWW. PMID- 11780706 TI - Barriers to STD/HIV prevention on the Internet. AB - Using the Internet as a mode for health promotion is appealing. There are important methodological considerations to the approach, but there are also important reasons why people will and will not participate in Internet interventions. This is a report on data from 4601 people who completed an online survey of sexual risk behavior in 2000. Most indicated they would visit a website for STD/HIV prevention information (61%), but fewer would open an E-mail (45%) or chat (30%) about the topic. Top reasons for rejecting website, E-mail and chat room education about STD/ HIV are given. Logistic regression results showed men who have sex with men (MSM) and persons with a history of testing for STD are consistently more likely to endorse STD/HIV prevention through chat rooms (MSM 1.8, STD testers 1.3), E-mail (MSM 1.6, STD testers 1.2) and websites (MSM 1.8, STD testers 1.2). The data demonstrate the Internet may facilitate health promotion among MSM who may not be reached in a publicly funded STD prevention setting. The Internet may also act as a good adjunct to STD information obtained in clinic settings among those who seek STD testing. PMID- 11780707 TI - Consumer health information seeking on the Internet: the state of the art. AB - Increasingly, consumers engage in health information seeking via the Internet. Taking a communication perspective, this review argues why public health professionals should be concerned about the topic, considers potential benefits, synthesizes quality concerns, identifies criteria for evaluating online health information and critiques the literature. More than 70 000 websites disseminate health information; in excess of 50 million people seek health information online, with likely consequences for the health care system. The Internet offers widespread access to health information, and the advantages of interactivity, information tailoring and anonymity. However, access is inequitable and use is hindered further by navigational challenges due to numerous design features (e.g. disorganization, technical language and lack of permanence). Increasingly, critics question the quality of online health information; limited research indicates that much is inaccurate. Meager information-evaluation skills add to consumers' vulnerability, and reinforce the need for quality standards and widespread criteria for evaluating health information. Extant literature can be characterized as speculative, comprised of basic 'how to' presentations, with little empirical research. Future research needs to address the Internet as part of the larger health communication system and take advantage of incorporating extant communication concepts. Not only should research focus on the 'net-gap' and information quality, it also should address the inherently communicative and transactional quality of Internet use. Both interpersonal and mass communication concepts open avenues for investigation and understanding the influence of the Internet on health beliefs and behaviors, health care, medical outcomes, and the health care system. PMID- 11780708 TI - Receiving social support online: implications for health education. AB - Online support groups are expanding as the general public becomes more comfortable using computer-mediated communication technology. These support groups have certain benefits for users who may not be able to or do not have the desire to attend face-to-face sessions. Online support groups also present challenges when compared to traditional face-to-face group communication. Communication difficulties may arise resulting from lack of visual and aural cues found in traditional face-to-face communication. Online support groups have emerged within health care as a result of the need individuals have to know more about health conditions they are confronting. The proliferation of these online communities may provide an opportunity for health educators to reach target populations with specific messages. This paper reviews the development of health related online support groups, examines research conducted within these communities, compares their utility with traditional support groups and discusses the implications of these groups for health education. PMID- 11780709 TI - How individuals coping with HIV/AIDS use the Internet. AB - Although identified 20 years ago, HIV/AIDS remains among the most serious disease epidemics of modern times. Because of the stigmatization associated with infection, no health crisis has rivaled HIV/AIDS in underscoring the need for emotional, informational and instrumental support. The critical role that support plays in coping with HIV/AIDS is well documented. Adults with HIV/AIDS have utilized traditional means of support--family, friends and community-based service organizations--in coping with their illness. Recently, however, the Internet has been recognized as a potential avenue for support. Although the Internet may prove promising, little is known about how the wide array of resources available via the Internet is used. The purpose of this study was to investigate how individuals with HIV/AIDS use the Internet in coping with their illness. This research study employed a descriptive qualitative design that used in-depth, semi-structured, face-to-face interviews for data collection. The sample of 10 purposefully selected individuals living with HIV/AIDS reflected diversity in gender, age, race, education, employment, number of years living with HIV/AIDS and Internet use. Data analysis guided by the constant comparative method revealed four themes. Individuals with HIV/AIDS use the Internet for finding information, making social connections, advocating and escaping. PMID- 11780710 TI - Enhancing learning through use of interactive tools on health-related websites. AB - The Internet offers a unique means of health promotion through the use of interactive tools like chat rooms, E-mail, hyperlinks and the like. This paper reports a study examining links between learning and interactivity of health related websites. We address three research questions. First, are tools of interactivity present in health-related websites? Second, how prevalent is the occurrence of these interactive tools for three relevant top level domains (TLD) (e.g. .com, .gov and .org)? Finally, are there differences in how representative websites of diverse TLDs employ these interactive tools along nine dimensions of interactivity? A content analysis of 30 websites revealed that while the majority of sites in our sample do use interactive tools, overall the occurrence is quite low. An examination of the use of tools of interactivity across three different TLDs revealed that .com sites used a greater number of tools, followed by .gov sites and, lastly, .org sites. We also found support for our third research question, that different TLDs employ these tools of interactivity differently. How these differences may impact learning are discussed. PMID- 11780711 TI - Can health professionals learn qualitative evaluation methods on the World Wide Web? A case example. AB - The Enhancing Data Utilization Skills through Information Technology (EDUSIT) project trained Maternal and Child Health professionals to collect, analyze and interpret data via a year-long web-based course. The overall goal of the project was to strengthen the technology and analytic skills of the public health workforce. This article describes and analyzes a web-based module for training public health professionals to use qualitative research and evaluation methods that was one of six offered within the EDUSIT project. The qualitative module consisted of six units: overview of qualitative methods, planning qualitative studies, conducting field observations, qualitative interviewing, analyzing qualitative data and presenting qualitative findings. Evaluation results found no statistically significant changes in specific knowledge or beliefs about qualitative methods. However, the change in participants' self-efficacy was statistically significant. Participants' self-reports also showed significant changes in perceived skill levels in 'collecting qualitative data through an interview' and 'analyzing and interpreting qualitative data'. Most participants rated each lesson within the qualitative methods module as valuable, and most found the teaching methods used satisfactory, emphasizing the value of both the didactic teaching and the practical exercises and team project. The most common difficulty reported was finding the time to complete the module requirements while also working full-time. Implications of these findings for web-based teaching of public health professionals are discussed. PMID- 11780712 TI - Online research to guide knowledge management planning. AB - The current paper describes the process and results of an effort to find a way to effectively manage and diffuse prevention knowledge. This study shows the role that today's communication technologies can play in ensuring collaboration and participation in both the design and use of a knowledge management system (KMS) for prevention research, practice and policy. In the context of this study, 'prevention research' includes primary through tertiary prevention efforts consistent with general applied public health research in the US. An online Delphi study was used to engage a set of prevention research constituencies in the design of a mechanism to enhance the potential for effective technology transfer. A three-round Delphi was conducted with 58 stakeholders and key informants involved in prevention: government-level policy makers, researchers and front-line practitioners. The study resulted in consensus on 34 functions and 32 output/content elements of a proposed web-based KMS called PreventionEffects.net. The paper also describes the implications of both the processes of development and the benefits of the proposed system for those interested in prevention. PMID- 11780713 TI - Planning cancer prevention strategies based on epidemiologic characteristics: an Egyptian example. AB - BACKGROUND AND METHODS: We describe the epidemiology, cancer prevention strategies, and educational messages to be learned from four characteristic cancers in Egypt: urinary bladder, liver, lung, and early-onset colorectal cancers. RESULTS: For bladder cancer, effective and convenient treatment of schistosomiasis, using social marketing and mass media in public and medical education has contributed dramatically to primary prevention of bladder cancer in Egypt. For liver cancer, educating hospital administrators to remove structural barriers to good practice may help the control of hepatitis transmission and related liver cancer. For lung cancer, the 50-year American experience for controlling tobacco smoking, beginning with physicians, could be very effective in Egypt and other countries with increasing smoking rates in the young so as to avert the expected epidemics of lung cancer. For colorectal cancer, more attention to physician and public education about the importance of interviewing colorectal cancer patients about a family history of cancer and the screening of at-risk families could be very effective in early detection of colorectal cancer. CONCLUSION: Countries with similar cancer epidemiology experience should make use of successful cancer prevention and education strategies that could be translated from the Egyptian experience. PMID- 11780714 TI - A review of physical and mental health in homeless persons. AB - OBJECTIVE: To review the physical and mental status in homeless people. DATA SOURCES: A MEDLINE database search covering 5 decades was supplemented by tracing back through references from existing review work. Over 200 articles were extracted, and 106 were selected for review. MAIN FINDINGS: Homeless persons suffer frequently from physical health problems like tuberculosis, asthma, bronchitis, HIV infection, and as a consequence, they run an increased risk for premature mortality. The prevalence of mental disorders among homeless individuals varies from 80-95% in the USA, Australia, Canada, Norway, and Germany to 25-33% in Ireland and Spain. The most prominent mental disorders among the homeless, which vary from country to country, are depression, affective disorders, substance abuse, psychotic disorders, schizophrenia, and personality disorders. CONCLUSION: Homelessness is a major public health problem that should have our special interest. PMID- 11780715 TI - Cutaneous leishmaniasis in Israel in the era of changing environment. AB - BACKGROUND: Cutaneous leishmaniasis (CL) is a zoonotic disease, endemic and notifiable in Israel. The vectors are sandflies of the genus Phlebotomus, the hosts are mainly field rodents. The infective agents are Leishmania parasites. Ph. papatasi is the recognized vector of L. major, while Ph. sergenti is considered to be the vector of L. tropica. AIM: To increase awareness of leishmaniasis, enhance surveillance, and improve reporting. METHODS: Morbidity data were obtained from disease notifications reported to the Department of Epidemiology of the Israeli Ministry of Health. RESULTS: The annual number of reported CL cases during the period 1961-2000 varied between less than 10 to over 250, with rates varying between 0.13 to over 7 per 100,000. Two peaks, between 1967-1969 and 1980-1982, are clearly seen. These peaks reflect environmental changes caused by the introduction of non-immune people (mainly Jews) into the area of endemic foci, enhanced urbanization by expansion of settlements bordering this area, agricultural/industrial projects, and most probably the effect of Global Warming. Recently, an increasing trend in the prevalence of the disease has been reported also by the Palestinian Authority and countries in the Mediterranean basin, reflecting shared changes in modern demographic and environmental conditions. These factors include population growth and movements, as well as ecological changes. CONCLUSIONS: Cooperation of the Ministries of Health and Environment of the countries of the whole Middle East region in combating the vectors and the reservoirs in animal hosts are a major need. PMID- 11780716 TI - Characteristics of comorbidity in adult asthma. AB - BACKGROUND: Although asthma in adult patients is responsible for a large proportion of the morbidity in primary care practice, there is minimal published information on comorbid conditions associated with asthma. The objective of this study was to compare the prevalence of common medical conditions in adult asthmatic and non-asthmatic subjects. METHODS: A case control study was conducted on a population of 4341 men and women aged 18 years or older. The prevalence of 17 medical conditions was measured in asthmatics (n = 141) and non-asthmatic subjects (n = 423) registered with a primary care practice. RESULTS: The most prevalent conditions among asthmatics were: hypertension (22.7%), diabetes (16.3%), and hiatal hernia with or without gastroesophageal reflux (13.5%), while cerebrovascular accident (1.0%) and depression (0.7%) had the lowest prevalence. The most common conditions among non-asthmatics were: hypertension (25.1%), obesity (13.9%), and diabetes (12.5%), while sinusitis, and glaucoma (1.4%) had the lowest prevalence. The odds ratios in asthmatics vs. non-asthmatics were for hiatal hernia 5.83 (95% confidence interval [CI] 2.56-13.5, p < 0.0001), chronic bronchitis 6.31 (95% CI 2.58-15.70, p < 0.001), gastric ulcer 2.55 (95% CI 0.95 6.81, p < 0.04), sinusitis 6.3 (95% CI 1.69-25.29, p < 0.001), and glaucoma 3.1 (95% CI 0.90-11.0, p < 0.04). CONCLUSIONS: A different pattern of comorbid conditions was observed. Recognition of these conditions is essential for the proper management of asthma and coexisting disorders. PMID- 11780717 TI - Mantoux testing of 7th graders in Tel Aviv, Israel. AB - As part of a countrywide program of tuberculin testing of 7th graders, 10,133 children were examined in the Tel Aviv area over the 3-year period, Septemer 1991 June 1994. Of these, 655 were from families recently arrived from the former Soviet Union (I), and 9478 from long-time resident families of Israel (L). Of the I group 537 had received BCG at least once (82.0%), of the L group 5306 (56.0%). In the nonvaccinated I group 33.9% had reactions of 10 mm or more (clinically significant) while the rate was 6.1% in the L group, a statistically highly significant difference. In the vaccinated I group the rate of clinically significant reactions was 49.3% as compared to 10.3% in the L group, also statistically a highly significant difference. In general, the clinically significant reactions were more commonly found in the I group as opposed to the L group. Both BCG vaccination and prior place of residence appear to be statistically significant independent variables. No cases of tuberculosis occurred among the entire population tested. These data provide a base for surveillance of tuberculosis risk in Tel Aviv specifically and Israel in general. PMID- 11780718 TI - Calcium intake in preschool children--a study of dietary patterns in a low socioeconomic community. AB - BACKGROUND: There is a lack of published data on sources and quantity of calcium intake in preschool children. STUDY OBJECTIVES: To assess calcium intake compared with the Dietary Reference Intake (DRI), to identify major food sources of calcium, and to compare dietary patterns of healthy preschool children who do and do not meet the calcium DRI. DESIGN: Cross-sectional study. SETTING: Primary care pediatrics practice at a large urban medical center. SUBJECTS: A group of 228 children aged 44 to 60 months in a low socioeconomic community. METHODS: Diet was assessed using three or four 24-hour recalls administered approximately three months apart to the parents. Nutrient values were computed using a dietary analysis program based on USDA values. RESULTS: Mean daily calcium intake was 852 mg/day (S.D., 271) and 44% reported mean calcium intake less than the DRI of 800 mg/day. Milk consumption accounted for 64.3% and cheese for 6.7% of the daily calcium intake. Multiple linear regression analysis adjusting for age, sex, race, body mass index, and total caloric intake confirmed the main contribution of mainly milk and, to a much lesser extent, cheese consumption, as determinants of calcium intake. All of the children who consumed less than 1.2 servings of milk (288 ml) milk per day reported mean daily calcium intake below the DRI. CONCLUSIONS: Calcium intake below the DRI may be common in preschool children in low socioeconomic communities, and is associated primarily with lower milk intake. These findings indicate the need to promote the consumption of low-fat milk in preschool children. PMID- 11780719 TI - Evaluation of the severity of chronic heart failure by the reactivity of peripheral vessels. AB - We developed a method to evaluate the severity of chronic cardiac failure by Doppler image analysis. Doppler images of the whole arterial lumen were consecutively recorded on video tape and the power spectrum (sum of intensity multiplied by frequency) of each frame was considered as an index of the blood flow volume (VI). The right brachial artery was occluded for 15-60 seconds by a occluding cuff, and was released quickly. The VI was determined until the VI returned to the level at rest and total VI was calculated as an O2 repayment. The O2 repayment rate (R-Rate) was calculated as a ratio of the O2 repayment divided by total VI during interruption. The cardiac function was evaluated by sub maximal exercise using bicycle ergometer and was compared with the R-Rate. The subjects were 22 patients (18 males and 4 females) with chronic cardiac failure of NYHA class I (9), class II (6), class III (4), class IV (3) and 12 healthy controls. R-Rate was almost unchanged by the duration of occlusion and showed positive correlation with exercise capacity. R-Rate decreased as the class of NYHA advanced. In conclusion, determination of reactive hyperemia can be used for objectively evaluating the severity of cardiac failure. Doppler sonography; cardiac failure; reactive hyperemia; peripheral circulation PMID- 11780720 TI - A case of influenza subtype A virus-induced fulminant myocarditis: an experience of percutaneous cardio-pulmonary support (PCPS) treatment and immunohistochemical analysis. AB - A 64-year-old man was admitted to the emergency center of Furukawa City Hospital because of common cold-like symptoms and hypotension. He was diagnosed as fulminant myocarditis with cardiogenic shock and arrhythmia elicited by influenza virus subtype A. Cardiac angiography, echocardiography and biopsy also showed myocarditis, and serum antibody titer to influenza virus subtype A was increased to 4-fold in paired serums. Treatments of both percutaneous cardio-pulmonary support (PCPS) and intra-aortic balloon pumping (IABP) were carried out to sustain the general circulation. PCPS treatment was discontinued on the 25th day of the admission, but IABP was continued. Finally, he died of multiple organ failure. The autopsy revealed myocardial necrosis with a slight fibrosis and a small amount of lymphocytic infiltration into the ventricular wall, which were compatible with restrictive myocarditis. Moreover, immunohistochemical analysis also showed the presence of viral antigens in cardiac myocytes. This case clearly showed that PCPS and IABP can be beneficial to sustain the general circulation in fulminant myocarditis, but cardiac pumping function failed completely to recover from myocardial damage. PMID- 11780721 TI - Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease. AB - The aim of the present study is to clarify in situ expression of platelet-derived growth factor (PDGF) and its receptors in different phases of inflammatory bowel disease (IBD). Tissues samples were obtained from 20 patients with ulcerative colitis (UC) and 29 with Crohn's disease (CD) at surgery. In situ hybridization and immunohistochemistry on frozen sections were performed for PDGF-A and -B and its alpha and beta receptors (alphaR and betaR). The area of active inflammation was infiltrated by abundant polymorphonuclear and mononuclear leukocytes, of which the latter expressed mRNA and proteins of PDGF-A, -B, and -alphaR and mRNA for PDGF-betaR. The area of active fibrosis, characterized by activated fibroblasts/ myofibroblasts, was juxtaposed to ulceration, which is induced as a repair process to tissue destruction. In these areas, activated fibroblasts/myofibroblasts were positive for mRNA and protein of PDGF-A, -B, alphaR, and -betaR. The expression of PDGF-A, -B, and -alphaR declined significantly in the scar area. Our results suggest that PDGF is not only important as an inducer of fibrosis in the repair phase but also it is involved in the active inflammatory phase possibly as a chemoattractant for mononuclear inflammatory cells. PMID- 11780722 TI - Effect of intra-articular administration of hyaluronan and cortisone on secondary osteoarthritis of the infected rabbit's knee. AB - Hyaluronan is known to play an important role in the healing of degenerative osteoarthritis. But there is no clear consensus how it effects on osteoarthritis compare to cortisone. The purpose of the research was to determine the comparative effects of hyaluronan and cortisone on the healing of degenerative osteoarthritis. A rabbit model used in which a degenerative osteoarthritis were created in the articular cartilage by the inoculation of Staphylococcus Aureus (S. Aureus). The rabbits divided into two groups namely injected with hyaluronan (group A) and cortisone (group B) at days 20, 23 and 26. After hyaluronan and cortisone injections for treatment of osteoarthritis at day of 25 and 35 six rabbits (each of three injected with hyaluronan and cortisone) and at day 50 (six of injected with hyaluronan and five of cortisone) were sacrified. In biopsies obtained from these knees both articular cartilage degeneration and inflammation around the joint were examined by light microscopy. It was seen that the histopathologic findings were consistent with active chronic inflammation at day 10, followed by chronic inflammation. At day 5 of treatment the degeneration decreased (60%) in group A, and clinical findings disappeared after day 9 of treatment. At day 15 of hyaluronan treatment the degeneration degree regressed and at day 30 absolutely healed (all except one). In group B, at day 5 of treatment, the clinical findings disappeared and the healing rate was 72%. At day 15 of cortisone treatment, the degeneration slightly increased and at day 30 the degeneration degree increased more than that day of 15. The results showed that cortisone is effective in the treatment of cartilage degeneration and inflammation early in the course of the septic arthritis whereas the therapeutic effect of hyaluronan is higher late in the course of the disease. Further studies are required in order to understand the effectiveness of the combined or consecutive use of these drugs in degenerative osteoarthritis. PMID- 11780723 TI - Glomerular endothelial cells are maintained by vascular endothelial growth factor in the adult kidney. AB - Vascular endothelial growth factor (VEGF) is known to maintain endothelial cells of immature vessels and is constitutively expressed in the kidney from the embryo to adult. We tested the hypothesis that VEGF activity is needed to maintain glomerular endothelial cells in the adult. Neutralizing antibody to VEGF165 was intraperitoneally administered to mice for 3 days to strongly suppress its intrinsic activity. On the fourth day, mice were sacrificed and tissues were examined by light and electron microscopies. Vascular casts of renal vessels were observed by a scanning electron microscopy. Distribution of the administered antibody and expressions of VEGF and Flk-1 were examined immunohistochemically. The suppression of endogenous VEGF activity caused swelling and vacuolation of endothelial cells and obstruction of capillaries in the glomerulus. Other tissues were not impaired significantly. The administered antibody was specifically localized to the glomerulus, and was found more predominantly in the juxta medullary than in the cortical glomerulus. This pattern of antibody deposition was similar to that of Flk-1. VEGF expression in the glomerulus was compensatively elevated by the antibody treatment. These results show that demand for VEGF signaling in the glomerulus is much higher than in other tissues, probably to protect its endothelial cells against high tension for blood filtration. This demand may be fulfilled by enriched signaling through the Flk-1 in the glomerulus. PMID- 11780724 TI - Differential effects of chlorpromazine on two vasoconstrictor tones in the rat. AB - Hindquarter compensator tone (HCT) is referred to as the sympathetic vasoconstrictor tone to the hindquarters of the rat induced by such hypotensive interventions as pentobarbital anesthesia, nitrate administration and blood loss. The aim of this study is to observe whether chlorpromazine (CPZ) injected intravenously in rats (0.5 mg/kg) inhibits the following two different kinds of vasoconstrictor tone: HCT induced by pentobarbital and the renal tone which is normally present in the conscious state. Rats were implanted with an electromagnetic flow probe around the terminal aorta or the left renal artery. The right common carotid was cannulated for mean arterial pressure (AP). Regional peripheral resistance (hind-quarter resistance [HQR] or renal resistance [RR]) was calculated as AP divided by regional flow. In rats under pentobarbital anesthesia, after CPZ, ganglionic blockade with hexamethonium bromide (25 mg/kg) did not decrease HQR. However, in conscious rats after CPZ, blockade decreased RR significantly. These findings indicate that CPZ inhibits HCT almost completely but scarcely decreases the renal tone and further suggest that HCT and the renal tone are generated by different mechanisms. PMID- 11780725 TI - Acute abdominal pain preceding cutaneous manifestations of varicella zoster infection after allogeneic bone marrow transplantation. AB - The current communication describes clinical findings in two recipients of allogeneic bone marrow transplantation (BMT) with varicella zoster virus infection who complained of acute severe abdominal pain preceding cutaneous manifestations. Physical examination, laboratory data and gastroscopic findings were nonspecific. In these cases, acyclovir was very effective for the symptoms. Varicella zoster virus infection should be suspected in BMT recipients who have rebellant acute abdominal pain but no characteristic skin eruptions. PMID- 11780726 TI - Enhancing the control of force in putting by video game training. AB - Even if golf video games provide no proprioceptive afferences on actual putting movement, they may give sufficient substitutive visual cues to enhance force control in this skill. It was hypothesized that this usefulness requires, however, two conditions: the video game must provide reliable demonstrations of actual putts, and the user must want to use the game to make progress in actual putting. Accordingly, a video game was selected on the basis of its fidelity to the real-world game. It allowed two different methods of adjusting the virtual player's putting force in order to hole a putt: an analogue method that consisted of focusing on the virtual player's movement and a symbolic method that consisted of focusing on the movement of a gauge on a scale representing the virtual player's putting force. The participants had to use one of these methods with either the intention of making progress in actual putting or in a second condition to simply enjoy the game. Results showed a positive transfer of video playing to actual putting skill for the learning group and also, to a lesser degree, for the enjoyment group; but only when they used the symbolic method. Results are discussed in the context of how vision may convey force cues in sports video games. PMID- 11780727 TI - Dutch Musculoskeletal Questionnaire: description and basic qualities. AB - A questionnaire ('Dutch Musculoskeletal Questionnaire', DMQ) for the analysis of musculoskeletal workload and associated potential hazardous working conditions as well as musculoskeletal symptoms in worker populations is described and its qualities are explored using a database of 1575 workers in various occupations who completed the questionnaire. The 63 questions on musculoskeletal workload and associated potentially hazardous working conditions can be categorized into seven indices (force, dynamic and static load, repetitive load, climatic factors, vibration and ergonomic environmental factors). Together with four separate questions on standing, sitting, walking and uncomfortable postures, the indices constitute a brief overview of the main findings on musculoskeletal workload and associated potentially hazardous working conditions. Homogeneity of the indices is satisfactory. The divergent validity of the indices is fair when compared with an index of psychosocial working conditions and discomfort during exposure to physical loads. Worker groups with contrasting musculoskeletal loads can be differentiated on the basis of the indices and other factors. With respect to the concurrent validity, it appears that most indices and factors show significant associations with low back and/or neck-shoulder symptoms. This questionnaire can be used as a simple and quick inventory for occupational health services to identify worker groups in which a more thorough ergonomic analysis is indicated. PMID- 11780728 TI - Individual differences in tracking. AB - The present experiment compared differences in response strategy of participants performing a two-dimensional tracking task at three different levels of task difficulty. Twelve participants tracked an iconic aeroplane target as accurately as possible for nine repeated trials each of 5 min duration. The random input and individual response output were calculated in terms of direction and velocity. Specifically, for each 200-ms sample period, a calculated combination of eight trajectories and three velocities provided a 24 combinatorial description of both random input and participant response. Distributions across these combinations represent descriptive results and reflect individual characteristics. The distributions were compared using the technique of correspondence factor analysis. The outcome of this multidimensional method was that first, between participants discrimination was best served by the up-vertical and low-velocity combination and, second, that the former pattern typified poor performers, while more skilled individuals used all directional options at the highest velocity level. Implications for individualized controls are examined. PMID- 11780729 TI - Activity analysis of English Premiership rugby football union refereeing. AB - Little is known about the physiological demands placed on officials during sporting activities. The purpose of this study was to ascertain the movement activities of referees during English Premiership rugby football union matches, and to determine the frequency and duration of these activities. Nine referees who were ranked in the top 20 referees in England were videotaped during a total of 19 matches. During playback of the videotapes, a single observer coded the referees' activities into one of six distinct categories (standing, walking forwards, walking backwards, jogging, running and sprinting) using a computerized video editing system (Observer Video-Pro). The referees were timed over a 20 m distance for the modes of locomotory activity, and the average velocity of the referee for each activity was used to calculate the total distance covered in each mode of activity during matches. The total distance covered during a match was (chi +/- SD) 8581 +/- 668 m. The mean percentage of total playing time spent in each activity was: standing still, 37.0 +/- 11.0%; walking forward, 29.5 +/- 7.2%; walking backward, 9.9 +/- 3.2%; jogging, 12.8 +/- 3.2%; running, 9.8 +/- 2.3%; and sprinting, 1.0 +/- 0.4%. There were a total of 672 transitions between modes of activity during a match. The results of this study suggest that refereeing top English rugby football union matches is physically demanding. Although the major physiological load is placed on the oxygen transport system, frequent sprint bouts and the associated requirements for acceleration and deceleration impose additional metabolic demands on referees. This information may be used in the design of physical training programmes to optimize performance in referees. PMID- 11780730 TI - Technical note: repeatability of measurement in determining stature in sitting and standing postures. AB - The aim of this study was to determine the effect of sitting and standing postures on the repeatability of a stadiometer designed to detect small variations in spinal length. Two groups of ten healthy subjects, with no previous or known history of back problems, participated in this study. One group was measured in the standing posture, while the other group was measured in a sitting posture. All subjects gave informed consent to participate in this study. Subjects had a set of landmarks defining the spinal contour marked on their backs and then stood in the stadiometer for three series of ten measurements to be performed. At the end of each measurement, the subjects were requested to move away from and then be repositioned in the stadiometer. Subjects improved the repeatability across the measurement series. At the end of the second measurement series, all subjects presented mean standard deviations of 0.43 +/- 0.08 mm (range 0.30-0.50 mm) in the standing posture. In the sitting posture, deviations of less than 0.05 mm were obtained only at the end of the third measurement series (0.48 +/- 0.08 mm; range 0.34-0.62 mm), suggesting that this posture required three measurement series before repeatable measurements could be assured rather than two in the standing posture. PMID- 11780731 TI - A comparison of the coverage of clinical medicine provided by PASCAL BIOMED and MEDLINE. AB - The bibliographic databases PASCAL BIOMED and MEDLINE, available both at SilverPlatter, were compared for their coverage of clinical medicine. The main objective of the study was to identify the information in PASCAL BIOMED that is supplementary to MEDLINE. In PASCAL BIOMED and MEDLINE 10 searches were performed, all limited to publication year 1996. Search profiles in PASCAL BIOMED were free text only, while in MEDLINE they were mainly composed of MeSH headings, with additional free text. Search results were analysed for numbers of (relevant) references retrieved, unique and duplicate references, precision and uniqueness ratio. Also the presence of abstracts in both databases, and the abstract language and the presence of English descriptors and identifiers in PASCAL BIOMED were studied. MEDLINE contained more relevant information than PASCAL BIOMED on nearly all topics studied. The precision of the PASCAL BIOMED searches varied from 29 to 87% (median = 68%) and of the MEDLINE searches from 20 to 91% (median = 66%). The uniqueness ratio in PASCAL BIOMED varied from 0 to 33% (median = 20%) and in MEDLINE from 28 to 83% (median 37%). Considering the numbers of relevant and unique references retrieved, MEDLINE performed better than PASCAL BIOMED. Yet a sizeable proportion of the relevant references were unique to PASCAL BIOMED. Probably PASCAL BIOMED would have performed better if lists of descriptors had been accessible in the database, preferably with support to trace them. PMID- 11780732 TI - The Cunningham Fellowship: three international points of view. AB - The Medical Library Association Cunningham Fellowship Program provides funds for one medical librarian per year from outside the United States or Canada to work and learn in United States or Canadian medical libraries for a period of 4 months. An overview of the Cunningham Fellowship is presented from three different points of view-that of a Medical Library Association member who has worked closely with the Cunningham Fellowship programme, and two former Cunningham Fellows. Anita Verhoeven, who relates her impressions of American culture, architecture and art, was the 1998 MLA Cunningham Fellow and visited 33 libraries, met 171 librarians, visited prestigious universities and attended a Medical Library Association meeting. Ioana Robu, the 1997 Cunningham Fellow, visited 15 libraries in 13 cities during her experience. She describes the process of applying for the fellowship and assesses the impact that the 1997 Cunningham Fellowship has made on her life, her library and medical librarianship in Romania. An overview of the Cunningham Fellowship is also given, which includes the history, the application process, the requirements of the fellowship and the time table of the fellowship. PMID- 11780734 TI - Turning research priorities into answerable questions. PMID- 11780733 TI - Biomedical information @ the speed of light: implementing desktop access to publishers' resources at the Paterson Institute for Cancer Research. AB - Shortly after midnight every Thursday morning, a list server in Massachusetts delivers an electronic table of contents message to the Kostoris Medical Library at the Paterson Institute for Cancer Research in Manchester, UK. The messageins details of the latest edition of the New England Journal of Medicine, complete with hyperlinks to the full text of the content online. Publishers' electronic current awareness services have been integrated into the dissemination process of the Library service to enhance the speed of communication and access to full text content. As a means of promoting electronic journal use, a system of e-mail delivery coupled with fast Internet access has allowed a migration from paper based current awareness alerting to a seamless online product. PMID- 11780735 TI - REALISE-ing their potential?: Implementing local library projects to support evidence-based health care. AB - Librarian involvement in Evidence-based Health Care provides many opportunities at a local level. Unfortunately, the potential for innovative projects to inform future developments is generally lost by a failure to 'pass the baton'--to identify lessons learnt and transferable principles. The 'Library Support for Evidence-based Health Care' Project, funded by the NHS Executive Northern and Yorkshire, resulted in the implementation of locally responsive packages of hardware and software in six of the Region's libraries. The opportunity to evaluate the collective experience of these sites, and to synthesize principles of good practice, was provided by a separately funded post-hoc evaluation, the Research Evaluation to Audit Library and Information Support for EBHC (REALISE). This paper reports on how this evaluation was conducted, documents the strengths and weaknesses of the Project itself, and attempts to provide a checklist for use in similar projects. The paper concludes by outlining the relevance of the findings to the introduction of planned organizational approaches to quality (clinical governance) and the development of local implementation strategies across the UK, required by the NHS Information Strategy, Information for Health. PMID- 11780736 TI - Searching for high-quality evidence to prepare patient information. AB - OBJECTIVES: To help those preparing patient information by developing a search protocol for finding evidence on treatments that would maximize rigour, relevance and completeness. To apply the search protocol in one example area, 'early breast cancer'. METHODS: Development--a multidisciplinary group listed evidence sources and assigned them to 'rigour of methods' bandings and also assessed their completeness. A search protocol was made by ranking evidence sources by rigour and then by completeness. Application-the protocol was used to search for information on treatments for early breast cancer. RESULTS: Eighteen evidence sources provided details of their methods. Thirteen sources were assigned to Band A ('key source') and two sources to Band B ('some doubt about rigour but nevertheless useful'). The 15 Band A and B sources were ordered into a search protocol and used to identify 24 pieces of evidence about early breast cancer. Ten reviews were excluded (as irrelevant), leaving 14 useful pieces of evidence based information to help inform patient information. CONCLUSIONS: Those preparing patient information on treatments for early breast cancer would find 14 pieces of useful evidence. It remains to be seen how far these pieces of evidence would answer questions that patients might pose about treatments. PMID- 11780737 TI - Hospitals and consumer health information in New Zealand: the role of the library. AB - A research project was conducted with the primary objective of finding out what New Zealand hospitals are doing about providing consumer health information to patients, and specifically, the role played by hospital libraries. A database was compiled of all New Zealand hospitals, both public and privately funded. An individual responsible for consumer health information was identified at each hospital and a questionnaire sent directly to them. A 64% response rate was achieved, representing 196 hospitals. Fifty-four hospitals reported having an in house Library or Information Centre for patients, but the materials and services provided varied widely. Results from this survey show that the provision of consumer health information in the hospital sector in New Zealand is ad hoc, and libraries are not necessarily involved. PMID- 11780738 TI - Improving standards in the scientific biomedical community in Romania by using journal ranking to improve journal quality. AB - The paper articulates the problems of journal publication in a relatively small country such as Romania where locally (i.e. nationally) published journals include most of the national medical scientific output. The starting point was a study ordered by the Cluj University of Medicine and Pharmacy Scientific Council, for the purpose of obtaining an objectively ranked list of all current Romanian biomedical journals that could be used in the evaluation of the scientific activity of the university academic staff. Sixty-five current biomedical journals were identified--of which more than half were new titles that had appeared over the past 5 years. None of these are included in the Science Citation Index or Journal Citation Reports (JCR). A set of criteria was used for ranking the journals: peer review, inclusion in international databases, publication time lag, language of articles and abstracts, journal specific index and domestic impact factor. The period covered, along with tools and formulas used are presented. The problems of Romanian biomedical journals as well as ways of improving publishing standards are discussed. Also emphasized is the necessity for increased awareness in the medical scholarly community and the role of the library in this respect. PMID- 11780739 TI - Medical illustration: from caves to cyberspace. AB - The human body has been depicted in ancient cave-paintings, in primitively sculpted figures, and through all the ages in various forms of artistic expression. The earliest medical texts were descriptive but not illustrated. Later, as it became clear that knowledge of the human body and all its systems was essential to the practice of healing, texts were accompanied by illustrations which became an integral part of the teaching process. The illustrators included artists, whose interest was primarily artistic, but who were sometimes employed by surgeons or physicians to illustrate their texts. Occasionally, the physicians or scientists accompanied their texts with their own illustrations, and in the last century, medical illustration, in its infinite variety of techniques, has been developed as a profession in its own right. As knowledge was extended, permitted by social and cultural change, as well as by technological advances, the types of illustrations have ranged from gross anatomy through dissections showing the various organ systems, histological preparations, and radiological images, right up to the computerized digital imagery that is available today, which allows both static and dynamic two- and three-dimensional representations to be transmitted electronically across the world in a matter of seconds. The techniques used to represent medical knowledge pictorially have been as varied as the illustrators themselves, involving drawing, engraving, printing, photography, cinematography and digital processing. Each new technique has built on previous experience to broaden medical knowledge and make it accessible to an ever widening audience. This vast accumulation of pictorial material has posed considerable problems of storage, cataloguing, retrieval, display and dissemination of the information, as well as questions of ethics, validity, manipulation and reliability. This paper traces these developments, illustrating them with representative examples drawn from the inexhaustible store of documents accumulated over more than two millennia. PMID- 11780740 TI - History of medicine. PMID- 11780741 TI - Why historians of medicine need your help. PMID- 11780742 TI - Medical history for tomorrow--preserving the record of today. AB - This paper addresses the need to recognize the importance, and the challenges, of preserving the hugely expanding record of medicine today for historians of the future. We are faced not only with an increase in traditional publishing formats, but also with the rapid growth in electronic communications. Two celebrated medical cases, one from the late seventeenth century and one from the late twentieth, are used to illustrate the differences and the difficulties. The need for active and effective professional collaboration is stressed; libraries should work together to address these issues. PMID- 11780743 TI - Elizabeth Blackwell--the forgotten herbalist? AB - This article looks at the work of Elizabeth Blackwell (1707-1758), by all accounts the first British female herbalist. To raise funds to free her husband from debtors prison, she produced her hand drawn, engraved and coloured 'Curious Herbal' in 1735. Using the copies of the herbal in the British Library, the article will look at the circumstances surrounding production of the herbal, her influences and sources used, including the people who recommended production of the book to the Society of Apothecaries and some of the current projects to put her name back on the map. PMID- 11780744 TI - Standing on the shoulders of giants. PMID- 11780745 TI - A CD-ROM on medicine in literature. PMID- 11780746 TI - The Open University history of medicine CD-ROM. PMID- 11780748 TI - A healthy future for medical records? A view from South-West England. PMID- 11780749 TI - The Worshipful Society of Apothecaries of London and the history of medicine. PMID- 11780750 TI - Development of the national electronic library for mental health: providing evidence-based information for all. AB - There has been an explosion of mental health literature available on the Internet over the past 5 years, with current estimates placing the number of health related Websites at over 100,000. The scope and depth of each site is unique and this serves to contribute to the difficulty of finding reliable, high-quality literature. This paper details efforts being made within the UK to provide high quality, evidence-based mental health literature for patients, clinicians and health policy makers as part of the National electronic Library for Health project. PMID- 11780751 TI - Increasingly the health information professional's role in supporting evidence based practice requires familiarity with critical appraisal skills, resources and techniques. PMID- 11780752 TI - Molecular machinery involved in the insulin-regulated fusion of GLUT4-containing vesicles with the plasma membrane (review). AB - The GLUT4 facilitative glucose transporter protein is primarily expressed in muscle and adipose tissue and accounts for the majority of post-prandial glucose uptake. In the basal or non-stimulated state, GLUT4 is localized to intracellular membrane compartments sequestered away from circulating glucose. However, in response to agonist stimulation, there is a marked redistribution of the GLUT4 protein to the cell surface membrane providing a transport route for the uptake of glucose. This GLUT4 translocation can be divided into four general steps: (i) GLUT4 vesicle trafficking out of the storage pool, (ii) docking just below the cell surface, (iii) priming via the interactions of the SNARE proteins present on the vesicular and plasma membranes, and (iv) fusion of the GLUT4 vesicle with the plasma membrane. This review focuses on recent advances made in identification and characterization of the molecular events and protein interactions involved in these steps of insulin-stimulated GLUT4 translocation. PMID- 11780753 TI - The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review). AB - During the last 2 years, several novel genes that encode glucose transporter-like proteins have been identified and characterized. Because of their sequence similarity with GLUT1, these genes appear to belong to the family of solute carriers 2A (SLC2A, protein symbol GLUT). Sequence comparisons of all 13 family members allow the definition of characteristic sugar/polyol transporter signatures: (1) the presence of 12 membrane-spanning helices, (2) seven conserved glycine residues in the helices, (3) several basic and acidic residues at the intracellular surface of the proteins, (4) two conserved tryptophan residues, and (5) two conserved tyrosine residues. On the basis of sequence similarities and characteristic elements, the extended GLUT family can be divided into three subfamilies, namely class I (the previously known glucose transporters GLUT1-4), class II (the previously known fructose transporter GLUT5, the GLUT7, GLUT9 and GLUT11), and class III (GLUT6, 8, 10, 12, and the myo-inositol transporter HMIT1). Functional characteristics have been reported for some of the novel GLUTs. Like GLUT1-4, they exhibit a tissue/cell-specific expression (GLUT6, leukocytes, brain; GLUT8, testis, blastocysts, brain, muscle, adipocytes; GLUT9, liver, kidney; GLUT10, liver, pancreas; GLUT11, heart, skeletal muscle). GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intra-cellular compartments by dileucine motifs in a dynamin dependent manner. Sugar transport has been reported for GLUT6, 8, and 11; HMIT1 has been shown to be a H+/myo-inositol co-transporter. Thus, the members of the extended GLUT family exhibit a surprisingly diverse substrate specificity, and the definition of sequence elements determining this substrate specificity will require a full functional characterization of all members. PMID- 11780754 TI - Targeting motifs in GLUT4 (review). AB - The trafficking of the insulin-sensitive glucose transporter, GLUT4, is the paradigm of how cells control the movement of membrane proteins through intricate pathways of transport in response to external stimuli, and how, by doing so, regulate their function. The GLUT4 intracellularly sequestered in resting adipocytes and muscle cells becomes exposed on their surface in response to an increase in insulin levels and muscle contraction, where it facilitates glucose uptake. Ceasing of the stimuli is followed by endocytosis of the GLUT4 molecules exposed on the plasma membrane and their recycling to the original stores, where they are retained. This review discusses current understanding of the organelles that host GLUT4 and the motifs that mediate its trafficking. PMID- 11780756 TI - Apical transport of osteopontin is independent of N-glycosylation and sialylation. AB - Studies of how epithelial surface polarity into apical and basolateral domains is generated and maintained have proposed that carbohydrate modifications serve as apical targeting signals for proteins by interacting with lectin sorters. However, the experimental evidence in support of N-glycans, O-glycans and sialic acids mediating apical transport is still very controversial. This could be partly due to the fact that in most studies exogenously expressed proteins were analysed. One has, therefore, examined the role of carbohydrate moieties in apical targeting of the endogenous secretory protein osteopontin in MDCK cells. It was found, however, that sorting of osteopontin does not require N glycosylation of the protein itself nor that of other factors involved in the sorting process. Incubation of cells with the inhibitor of O-glycosylation benzyl alpha-GaINAc reduced the molecular weight of osteopontin by blocking sialic acid addition to O-glycans. Interestingly, also impairment of sialylation had no effect on polar secretion of the protein. Thus, the results show that both N glycans and sialic acids are not essential sorting signals, suggesting that inner core carbohydrates and/or a proteinaceous signal mediate apical targeting of osteopontin. PMID- 11780755 TI - GLUT2 in pancreatic and extra-pancreatic gluco-detection (review). AB - Detection of variations in blood glucose concentrations by pancreatic beta-cells and a subsequent appropriate secretion of insulin are key events in the control of glucose homeostasis. Because a decreased capability to sense glycemic changes is a hallmark of type 2 diabetes, the glucose signalling pathway leading to insulin secretion in pancreatic beta-cells has been extensively studied. This signalling mechanism depends on glucose metabolism and requires the presence of specific molecules such as GLUT2, glucokinase and the K(ATP) channel subunits Kir6.2 and SUR1. Other cells are also able to sense variations in glycemia or in local glucose concentrations and to modulate different physiological functions participating in the general control of glucose and energy homeostasis. These include cells forming the hepatoportal vein glucose sensor, which controls glucose storage in the liver, counterregulation, food intake and glucose utilization by peripheral tissues and neurons in the hypothalamus and brainstem whose firing rates are modulated by local variations in glucose concentrations or, when not protected by a blood-brain barrier, directly by changes in blood glucose levels. These glucose-sensing neurons are involved in the control of insulin and glucagon secretion, food intake and energy expenditure. Here, recent physiological studies performed with GLUT2-/- mice will be described, which indicate that this transporter is essential for glucose sensing by pancreatic beta-cells, by the hepatoportal sensor and by sensors, probably located centrally, which control activity of the autonomic nervous system and stimulate glucagon secretion. These studies may pave the way to a fine dissection of the molecular and cellular components of extra-pancreatic glucose sensors involved in the control of glucose and energy homeostasis. PMID- 11780758 TI - Considerations in measuring Potassium efflux from plant cells using 87Rb magnetic resonance. AB - In order to stay metabolically active, plant cells must transport Potassium ions across their plasmalemma. Ion transport is subject to many complex metabolic regulatory processes. Information on Potassium metabolism can be obtained with 87Rb NMR spectroscopy, using Rubidium as a congener for Potassium. However, due to the presence of the vacuole, another non-metabolic mechanism for ion flux regulation exists. Using simple biophysical arguments, it is shown that an increase in vacuole size, without a change in total cell volume, could initiate a change in Potassium efflux. This change in efflux can be significant, especially for large vacuoles. PMID- 11780757 TI - Expression, purification and secondary structure analysis of Saccharomyces cerevisiae vacuolar membrane H+-ATPase subunit F (Vma7p). AB - The vacuolar H+-ATPase is an acid pump found in virtually all eukaryotic cells. It shares a common macromolecular organization with the F1F0-ATPase, and some V ATPase subunits are structural and functional homologues of F-ATPase components. However, the vacuolar complex contains several subunits which do not resemble F ATPase subunits at the sequence level, and which currently have no specific function assigned. One example is subunit F, the Vma7p polypeptide of Saccharomyces cerevisiae. A recombinant form of Vma7p was expressed in Escherichia coli and purified to homogeneity. Mass spectroscopy confirmed a mass of 13460 Da for Vma7p, and dynamic light scattering showed that the polypeptide was globular and monodisperse even at high concentrations. Analysis of secondary structure by circular dichroism and FTIR showed that Vma7p comprises 30% alpha helix and 32-42% beta-sheet. The protein fold recognition programme 'Threader 2' produced highly significant matches between Vma7p and five alpha-beta sandwich folds. Relative proportions of secondary structure elements within these folds were broadly consistent with the spectroscopic data. Although Vma7p does not share sequence similarity with the F-ATPase epsilon subunit, the analysis suggests that the polypeptides not only have similar masses and assemble into homologous core complexes, but also share similar secondary structures. It is possible that the two polypeptides are homologous and perform similar functions within their respective ATPases. The production of high yields of homogeneous, folded, monodisperse protein will facilitate high resolution crystallography and NMR spectroscopy studies. PMID- 11780759 TI - Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine. AB - 1. Quercetin is a natural flavonoid present in vegetables, fruit and wine, and is known to inhibit sulphotransferase. Drugs are often taken orally and the intestinal mucosa is an early site of drug metabolism. The aims of this investigation were to study the inhibition of dopamine, (-)-salbutamol, minoxidil and paracetamol sulphation by quercetin in the duodenal mucosa and liver and to compare the IC50 in these tissues. 2. The rates (pmol min(-1) mg(-1)) of sulphation of 4-nitrophenol were 343+/-92 (liver) and 164+/-22 (duodenum; p = 0.031), of dopamine were 15+/-11 (liver) and 656+/-516 (duodenum; p = 0.049), of (-)-salbutamol 153+/-31 (liver) and 654+/-277 (duodenum; p = 0.018), of minoxidil were 156+/-47 (liver) and 105+/-7 (duodenum; n.s.), and of paracetamol were 229+/ 86 (liver) and 328+/-187 (duodenum; n.s.). 3. The IC50 of quercetin for 4 nitrophenol was 48+/-11 nM (liver) and 56+/-1 nM (duodenum, n.s.), for dopamine was 5.7+/-0.7 microM (liver) and 170+/-12 microM (duodenum, p < 0.0001), for (-) salbutamol was 54+/-4 nM (liver) and 16+/-8 microM (duodenum; p = 0.025), for minoxidil was 134+/-22 nM (liver) and 3+/-0.3 microM (duodenum, p = 0.013), and for paracetamol was 57+/-7 nM (liver) and 35+/-1 microM (duodenum; p = 0.0002). 4. Quercetin inhibited the sulphation of 4-nitrophenol, dopamine, (-)-salbutamol, minoxidil and paracetamol both in liver and duodenum. With dopamine, (-) salbutamol, minoxidil and paracetamol as substrates, quercetin was a more potent inhibitor in the liver than the duodenum. Such a difference may reflect the different composition of sulphotransferase forms in the liver and duodenum. PMID- 11780760 TI - Evaluation of the marmoset as a model species for drug glucuronidation. AB - 1. The in vitro glucuronidation of a wide range of compounds has been studied in microsomes prepared from marmoset liver and kidney. These studies have been undertaken to evaluate the marmoset as a model species for drug glucuronidation and for comparison with conjugation by other species. 2. The compounds studied were glucuronidated by marmoset liver microsomes to varying extents (e.g. naproxen CLint 0.4 microl min(-1) mg(-1), 1-naphthol CLint 43 microl min(-1) mg( 1)) Both marmoset and rat liver microsomes glucuronidated morphine at the 3 position (marmoset CLint 19 microl min(-1) mg(-1), rat CLint 6.3 microl min(-1) mg(-1)) but glucuronidation at the 6-position was below, the level of radiodetection in both species. 3. Interestingly, marmoset liver microsomes were able to catalyse the glucuronidation of the tertiary amine imipramine to a significant extent (0.05 nmol min(-1) mg(-1)). However, no glucuronidation was detected by rat liver microsomes. 4. Conjugation of a range of substrates was detectable by marmoset kidney microsomes in contrast to rat kidney microsomes, which only catalysed the glucurondation of bilirubin and 1-naphthol (CLint 17 microl min(-1) mg(-1) and 18 microl min(-1) mg(-1), respectively). 5. This report and previous work in dog and human tissue microsomes suggest that the marmoset may be an alternative animal model for human drug glucuronidation, especially when the pathway of drug glucuronidation is known to differ between lower laboratory species and man. PMID- 11780761 TI - Evaluation of 7-benzyloxy-4-trifluoromethylcoumarin, some other 7-hydroxy-4 trifluoromethylcoumarin derivatives and 7-benzyloxyquinoline as fluorescent substrates for rat hepatic cytochrome P450 enzymes. AB - 1. The aim of this study was to evaluate a number of derivatives of 7-hydroxy-4 trifluoromethylcoumarin (HFC) and 7-benzyloxyquinoline (7BQ) as novel fluorescent substrates for monitoring rat hepatic cytochrome P450 (CYP) enzyme specificity in a 96- well plate format. The HFC derivatives examined comprised 7-benzyloxy-4 trifluoromethylcoumarin (BFC), 2,5-bis(trifluoromethyl)-7-benzyloxy-4 trifluoromethylcoumarin (BFBFC), 3,5-bis(trifluoromethyl)-7-benzyloxy-4 trifluoromethylcoumarin (BTBFC), 2-(trifluoromethyl)-7-benzyloxy-4 trifluoromethylcoumarin (2TFBFC), 3-(trifluoromethyl)-7-benzyloxy-4 trifluoromethylcoumarin (3TFBFC) and 3-(trifluoromethoxy)-7-benzyloxy-4 trifluoromethylcoumarin (3TFMeOBFC). 2. The CYP specificity of the fluorescent probe substrates was examined using characterized liver microsomes from male Sprague-Dawley rats treated with beta naphthoflavone (BNF), sodium phenobarbitone (NaPB), isoniazid, pregnenolone-16alpha-carbonitrile (PCN), dexamethasone (DEX) and methylclofenapate to induce CYP1A, CYP2B, CYP2E, CYP3A, CYP3A and CYP4A forms, respectively. Studies were also performed with microsomes from baculovirus infected insect cells containing rat cDNA-expressed CYP1A1, CYP1A2, CYP2B1, CYP3A1 and CYP3A2. 3. BFC metabolism was most markedly induced by BNF and NaPB, whereas BFBFC metabolism was most markedly induced by PCN and DEX and BTBFC was not metabolized by rat liver microsomes. BFC was a high-affinity substrate for cDNA-expressed CYP1A1 and CYP2B1, whereas BFBFC exhibited a high affinity for CYP3A1 and CYP3A2. 4. The metabolism of 2TFBFC and 3TFBFC was induced by NaPB, PCN and DEX. 3TFBFC was a relatively specific substrate for cDNA-expressed CYP2B1, whereas 2TFBFC could be metabolized by CYP2B1, CYP3A1 and CYP3A2. 5. 3TFMeOBFC metabolism was markedly induced by BNF treatment and 3TFMeOBFC was extensively metabolized by cDNA-expressed CYP1A1. 6. The metabolism of 7BQ to 7 hydroxyquinoline was induced by treatment with PCN and DEX. 7BQ was a substrate for cDNA-expressed CYP3A2 and to a lesser extent for CYP3A1. 7. In summary, some of the HFC derivatives studied and 7BQ are useful fluorescent probe substrates for rat CYP enzymes. BFC appears to be a probe for CYP1A and CYP2B, 2TFBFC for CYP2B and CYP3A and 3TFBFC for CYP2B. While 3TFMeOBFC appears to be a relatively specific probe for CYP1A1, both BFBFC and 7BQ are good probes for the induction of CYP3A. PMID- 11780762 TI - Rapid conversion of tea catechins to monomethylated products by rat liver cytosolic catechol-O-methyltransferase. AB - 1. The metabolic O-methylation of several catechol-containing tea polyphenols by rat liver cytosolic catechol-O-methyltransferase (COMT) has been studied. 2. When (-)-epicatechin was used as substrate, its O-merthylation showed dependence on incubation time, cytosolic protein concentration, incubation pH and concentration of S-adenosyl-L-methionine. The O-methylation of increasing concentrations of (-) epicatechin followed typical Michaelis-Menten kinetics, and the apparent Km and Vmax were 51 microM and 2882 pmol mg protein(-1) min(-1), respectively, at pH 7.4, and were 17 microM and 2093 pmol mg protein(-1) min(-1), respectively, at pH 10.0. 3. Under optimized conditions for in vitro O-methylation, (-)-epicatechin, (+)-epicatechin and (-)-epigallocatechin were rapidly O-methylated by rat liver cytosol. In comparison, (-)-epicatechin gallate and (-)-epigallocatechin gallate vere O-methylated at significantly lower rates under the same reaction conditions. catalysed O-methylation of (-)-epicatechin and (-)-epigallocatechin was inhibited in a concentration-dependent manner by S-adenosyl-L-homocysteine, a demethylated product of S-adenosyl-L-methionine. The IC50 was approximately 10 microM. 5. In summary, the results showed that several catechol-containing tea polyphenols were rapidly O-methylated by rat liver cytosolic COMT. These observations raise the possibility that some of the biological effects of tea polyphenols may be exerted by their O-methylated products or may result from their potential inhibition of the COMT-catalysed O-methylation of endogenous catecholamines and catechol oestrogens. PMID- 11780763 TI - Plasma concentrations of individual tea catechins after a single oral dose in humans. AB - 1. Ten healthy volunteers ingested 1.5 mmole epicatechin gallate (ECg), epigallocatechin (EGC) or epigallocatechin gallate (EGCg) in a randomized crossover design. After deconjugation, catechins in plasma and 24-h urine samples were determined by high-performance liquid chromatography (HPLC). Antioxidant activity was measured in plasma by determining ferric reducing activity (FRAP). 2. The catechin levels in plasma after ingestion were significantly different: EGC rose quickly with a short elimination half-life (t1/2 elim = 1.7 h), ECg was intermediate in rise but slowest in decline (t1/2 elim = 6.9h), EGCg was slowest in rise but intermediate in decline (t1/2 elim = 3.9h). At 24h, EGC and EGCg had returned to base levels, but ECg was still elevated. Peak maximum varied between 1.3 (EGCg) and 5.0 micromol l(-1) (EGC). 3. Very limited interconversion (ECg- >epicatechin, EGCg-->EGC) occurred indicating that degallation is not required for uptake. 4. Up to 13.6% of the ingested EGC (partly methylated) was excreted in the urine, but ECg or EGCg were not detected. 5. EGC and ECg produced an increase in antioxidant activity in plasma, but with EGCg, no statistically significant effect was found. 6. The pattern of uric acid in plasma showed a clear resemblance with that of FRAP and linear regression analysis indicated a very significant relationship (R2 = 0.88, p < 0.0001). 7. It is concluded that tea catechins differ significantly in their pharmacokinetic behaviour. PMID- 11780764 TI - Evaluation of the strength of elbow flexors in patients with neuromuscular diseases. AB - In planning the optimum treatment for patients with neuromuscular diseases (NMD), it is essential to know as much as possible about their functional state. Assessment of the strength of certain muscles is the most direct measure of motor deficiency. In the development of normative data needed for patients with NMD, the use of torque measurements is required. Forty-nine patients (31 men and 18 women),f rom 18 to 54 years (mean age 33 +/- 8.9 years), were included in the study. Five groups of patients, each having one of five different NMDs, were formed. We tested unilaterally the biceps brachii muscle that normally generates the highest torque. For this purpose an eletronic brace enabling isometric measurements of torque during elbow flexion was designed. The patients produced three maximum voluntary elbow flexions that lasted about 3 s and separated by a pause of about 3 s. Force development was rapid with continuous build-up and isometric. About 15 s later the patients produced the last maximum voluntary elbow flexion, keeping it as stable aspossible for a period of 30 s. Patients with mitochondrial myopathy (MM), having the shortest mean half fatigue time (4.3 s), elicited the highest mean torque in both short maximum voluntary elbow flexions (1.34 Nm) as well as in the 30 s-long maximum voluntary elbow flexions. In contrast, patients with facioscapulohumeral muscular dystrophy (MD-FSH), having the longest mean half-fatigue time (15.4 s), elicited the lowest mean torque in both the short maximum voluntary (0.29 Nm) as well as in 30 s-long maximum voluntary elbow flexions. Patients with Becker muscular dystrophy (MD-B), having a mean half-fatigue time (11.1 s) slightly shorter than the patients with MD-FSH, elicited a higher mean torque in both the short (0.82 Nm) and the 30 s long elbow flexions. Finally, patients with limb-girdle muscular dystrophy (MD RM) and spinal muscular atrophy type 3 (SMA3), having a similar mean half-fatigue time (6.9 s for patients with MD-RM and 7.4 s for patients with SMA3), also elicited similar torque in both short (0.45 Nm for patients with MD-RM and 0.65 Nm for patient with SMA3) and 30 s-long elbow flexions. The results of the study show that the methodology developed to quantitative measure the torque of elbow flexions in patients with NMD enables the characteristics and natural course of NMD to be more objectively documented. Accordingly, the optimum treatmentforpatients with NMD could be restored. PMID- 11780765 TI - Correlation among Poincare plot indexes and time and frequency domain measures of heart rate variability. AB - PRIMARY OBJECTIVE: In order to corroborate the rported performance advantage of Poincare plot indexes as autonomic activity markers, the correlation among these indexes and those computed from the time and frequency domains were obtained. METHODS AND PROCEDURES: Starting from the RR series derived from the ECG of 21 healthy volunteers during five manoeuvres, longitudinal (L), transverse (T) axis, and autocorrelation (r) from Poincare plots, rMSSD and standard deviation (SD) in the temporal domain, and frequency domain indexes were computed. MAIN OUTCOMES AND RESULTS: Poincare plot indexes were correlated in a better way with the time indexes, rather than the spectral measures. A strong correlation (0.997) between L and SD was observed, while an underlying mathematical relationship was established for T vs rMSSD. CONCLUSIONS: Poincare plot indexes may be considered as equivalent or surrogates of the temporal ones, and they do not have a better performance as autonomic markers. PMID- 11780766 TI - Technical note: reference values of haematocrit in young people and relationship with altitude. AB - The purpose of this paper is to provide scientific basis for a unified standard reference value of haematocrit in young people in China. The reference values of haematocrit levels in healthy young people have been collected according to the Wintrobe methods; the relationship between the reference values of haematocrit in young people and altitude has been tested in this paper. It has been found that the reference value of haematocrit in young people increases when the altitude gradually increases, and such relationship is quite significant, The method of mathematical univariate regression analysis is used to deduce two regression equations: Y1 = 44.3 + 0.00357X +/- 3.7, and Y2 = 39.7+0.00318X +/- 2.6. If the altitude value of a s known, the particular area of China is known, the reference value of haematocrit in young people there can be calculated by means of the regression equations. Furhermore depending on the altitude, China can be divided into three districts: Qingzang District, Central District and Eastern District. PMID- 11780767 TI - Statistical analysis of healthy and malignant breast thermography. AB - Analysis of thermograms has often been subjective and has resulted in inconsistency in the diagnosis of breast diseases by thermography. The aim of this paper is to study the problem of subjective interpretation of breast thermograms and hence using thermography as an adjunct tool for breast cancer diagnosis. It ws proposed that the thermograms should be taken within the recommended screening period, classified and analysed in conjunction with an artificial neural network (ANN). Qualitative interpretation of thermal images can be carried out using an active contours algorithm. The 256 x 200 pixel image can be segmented as one of the inputs to the ANN. To achieve quantitative analysis of the breast thermograms, firstly the inputs of the ANN should be determined, so that the thermograms could be successfuly classified and based on the suggested inputs. PMID- 11780768 TI - Technical note: a compact data logger for ambulatory skin temperature measurement. AB - A miniature, body-worn data logger has been developed for multi-channel recording of small changes in skin surface temperature. The unit has been designed for small size, long battery life and high accuracy together with full programmability and an infra-red (contactless) transfer of parameters and data. Temperature is measured using thermistors with a resolution of 0.005 degrees C and an absolute accuracy of better than 0.05 degrees C. A comprehensive software package running on a laptop PC is used for initial setting of the logger parameters and downloading and displaying the temperature data. The present system records eight channels of temperature at intervals from 30 seconds to 99 minutes. It contains 64 K bytes of non-volatile memory allowing 3274 sets of readings including subject identification, battey status, date and time. The logger size is 55 mm x 31 mm x 9.5 mm and weighs 20 g. PMID- 11780769 TI - Technical note: simple vibroacoustic foetal stimulator. AB - PRIMARY OBJECTIVE: To build and test a simple vibroacoustic foetal stimulator. RESEARCH DESIGN: A vibroacoustic foetal stimulator was constructed and subjected to bench testing. Clinical trial was carried out in comparison to an electro laynx. MAIN OUTCOME AND RESULTS: Screening specificity of 98% and 100% sensitivity was achieved, with no decrease in specificity due to user's maladjustments. The device was characterized by simple use, maintenance and disinfection. CONCLUSIONS: The device is a good screening instrument for foetal health in prenatal care, despite its simplicity and low price. PMID- 11780770 TI - Technical note: a durable impeller pump with rolling bearing and purge system. AB - Our former works demonstrated that the authors' impeller pump could support the circulation of experimental animals for several months without harm to blood elements and organ function of the animals. The termination of the experiments was mostly related to wear of the mechanical bearing and the thrombosis along the bearing. To solve the bearing problem, a magnetic bearing was investigated in our laboratory, resulting in some new problems, such as complicated design and control, considerable energy consumption and lower reliability. Progress in developing an impeller pump for long-term application has been achieved recently. Instead of using a slide bearing, a rolling bearing system has been devised. Its service life is more than ten years due to a wear-proof roller made of ultra-high molecular weight poythene. In order to avoid thrombus formation, a special purge system was introduced to the bearing, thus saline with heparin can be infused through the bearing into the pump. Therefore, the bearing keeps working in the saline, and no thrombus will be formed along the beating. The animal experiments demonstrated that 30 cc fluid infusion per hour continuously or interruptedly is enough to prevent the thrombus formation. With these improvements, the impeller pump was continuously run for one year and no bearing wear was measured in the endurance test. The device weighing 150g is fully implantable, consumes around 9.6 W electric energy by delivering 9 l min(-1) blood flow against 120 mmHg mean pressure and reaches a highest total efficiency, 24.7%, of motor (including controller) and pump at this point, which can produce both pulsatile and non pulsatile flow according to the requirements. PMID- 11780771 TI - Effect of supra-lactate threshold training on the relationship between mechanical stride descriptors and aerobic energy cost in trained runners. AB - The aim of this study was to determine the effect of endurance training on the relationship between mechanical stride descriptors (stride rate and stride rate variability) and the aerobic energy cost that would be decreased by training in an all-out supra-lactate threshold run. Six long distance runners (175 +/- 6 cm; 72 +/- 9 kg; 27 +/- 4 years) performed two identical track tests before and after 8 weeks of supra-lactate threshold training: an incremental test and a constant load test at 50% of the velocity difference between the lactate threshold and *VO2max (vdelta50). During the constant load test, aerobic energy cost (EC), stride rate (SR) and stride rate variability (SRV) were measured. The constant load tests were carried out before and after training at the same absolute intensity, in order to compare stride mechanical descriptors. Our results show that after eight weeks of intermittent running at vdelta50, the velocity associated with *VO2max (v *V02max) increases (p = 0.03) due to the decrease of running economy (RE, p = 0.02), and not due to an increase in *VO2max (p = 0.5). EC remained unchanged with training (p > 0.1), but SRV was significantly reduced (p < 0.03). No relationship was observed before and after training between the stride rate variability and the aerobic energetic cost (rs < 0.5; p > 0.05). This study indicates that because of the initial level of the runners, endurance training has not induced an increased *VO2max but a decrease of the SRV. Further studies have to be conducted with more subjects in order to elucidate the mechanisms underlying this decrease in SRV which is observed with training. PMID- 11780772 TI - The action of isoprenaline on the electrophysiological properties of hypertrophied left ventricular myocytes. AB - The electrophysiological effects of the beta-agonist, isoprenaline, on hypertrophied left ventricular myocardium were measured to understand better the arrhythmic effects of beta-stimulation on the hypertrophied heart. Left ventricular hypertrophy was induced in guinea-pigs by constriction of the thoracic aorta. An age-matched sham-operated group served as controls. Isolated myocytes were held under voltage- and current clamp and the effect of isoprenaline on the L-type Ca2+ current, I(Ca), a Cl- current, I(Cl), and action potential morphology were measured. Cardiac growth was mirrored by cellular hypertrophy. I(Ca) and I(Cl) current density were reduced as myocyte hypertrophy progressed. The augmentation of I(Ca) and I(Cl) by isoprenaline was also reduced in hypertrophy, but no other characteristics of the two currents, or the dose dependency of the action of isoprenaline were a function of cardiac growth. Isoprenaline prolonged the action potential, but to a smaller extent in hypertrophied myocytes. This difference in action potential prolongation was abolished by glibenclamide. The changes to I(Ca) and I(Cl) in hypertrophy would not tend to increase triggered activity in this situation. Under maximum inotropic stimulation hypertrophied myocytes show action potential changes which are consistent with intracellular ATP depletion, and which could enhance the likelihood of re-entrant circuits. A simple diffusion model for oxygen is constructed to demonstrate the possibility of cellular hypoxia in hypertrophied myocytes. PMID- 11780773 TI - Transmission of rectal electric waves: is it through circular or longitudinal smooth muscle layers or both? AB - The rectum possesses electric activity in the form of pacesetter (PPs) and action potentials (APs). In recent studies we suggested that the waves are not initiated by the extrarectal autonomic innervation but might be triggered by a 'rectosigmoid pacemaker' and are transmitted in the rectal wall through the rectal musculature and not the enteric nerve plexus. To investigate whether the rectal waves are transmitted through the circular or longitudinal muscle layer, the rectum of 18 mongrel dogs was exposed under anesthesia through an abdominal incision. Three electrodes were applied to the rectal wall (longitudinal muscle layer) and another 3 electrodes to the circular muscle; the latter was exposed by splitting apart the fibers of the longitudinal muscle. Rectal electric activity and pressure were recorded from the 6 electrodes before and after performing individual myotomy of the rectal longitudinal (9 dogs), circular (9 dogs), and then the whole muscle layers (18 dogs). The myotomy was performed proximal to and between the electrodes. Pacesetter (PPs) and action potentials (APs) were recorded from the 3 electrodes on the longitudinal muscle but no waves were registered from those on the circular muscle. After longitudinal muscle myotomy was performed between electrodes 1 and 2, PPs and APs were recorded from electrode 1 but not 2 and 3 and when performed proximally to electrode 1, no waves were registered. The rectal pressure increased concomitantly with occurrence of APs. Circular muscle myotomy effected no change in the rectal electric activity recorded from the 3 electrodes applied to the longitudinal muscle. In total muscle myotomy, the electric waves were recorded from the electrodes proximal but not distal to the myotomy. We propose that the motile activity of the rectal longitudinal muscle is initiated by the electric activity which appears to be triggered by the rectosigmoid pacemaker, while that of the circular muscle fibers is believed to be initiated by the stretch reflex induced by rectal distension. This concept is evidenced not only by the current findings but also by the histologic structure of the rectal musculature being of the unitary type of smooth muscles. PMID- 11780774 TI - Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats. AB - Although accumulating evidence suggests that increased extracellular glutamate concentrations may play an important role in hypoxic-ischemic brain injury, dopamine and other catecholamines also seem to be involved. The N-methyl-D aspartate receptor antagonist MK 801 and moderate hypothermia (32-34 degrees C) are each known to be neuroprotective, but their combined effect on the release and metabolism of neurotransmitters is unknown. Seven-day-old pups (n: 150) underwent right common carotid artery ligation to induce hemispheric ischemia, and were later subjected to 120 minutes of hypoxia with 8% O2 and 92% N2O. Half the rats (Group I, n: 74) were subjected to normothermic conditions throughout the hypoxic period. Moderate hypothermia (30-32 degrees C) was induced in the other pups (Group II, n: 76) immediately after artery occlusion, and was maintained throughout the hypoxic period. Prior to inducing hypoxia, half of the rats in each group (Groups IA and IIA) received vehicle solution (0.9% NaCI) and the other rats (Groups IB and IIB) received MK 801 (0.5 mg/kg) subcutaneously at 45 and 120 minutes after occlusion. Intracerebral temperature was recorded every 15 minutes after occlusion. Infarct area (n: 40) was calculated after staining with 2% 2,3,5 triphenyltetrazolium chloride. Neuronal damage (n: 42) was assessed by quantifying CA1-CA3 neuronal loss at five hippocampal levels. The amount of damage to the monoamine system of the corpus striatum was determined based on the dopamine and 3,4 dihydroxyphenylacetic acid levels in the corpus striatum in both hemispheres (n: 46), as measured by high-pressure liquid chromatography and compared with normal control pups' values (n: 10). The normothermia/saline treated pups had significantly larger infarct areas than the MK 801 only, hypothermia only, or MK 801/hypothermia combination groups. Neuropathological examination and striatal tissue monoamine data also confirmed marked neuronal damage in this group. Although MK 801 treatment alone resulted in significantly smaller infarct area and less tissue damage than was observed in the normothermia/saline-treated group, the moderate hypothermia and the MK 801/hypothermia combination treatment groups both exhibited better neuronal protection, especially in the corpus striatum. The rats that received combined treatment also had a significantly lower mortality rate. PMID- 11780775 TI - Acute and delayed vasoconstriction after subarachnoid hemorrhage: local cerebral blood flow, histopathology, and morphology in the rat basilar artery. AB - The decreased local cerebral blood flow (LCBF) and cerebral ischemia that occur after subarachnoid hemorrhage (SAH) may be caused by acute and/or delayed vasospasm. In 36 Sprague-Dawley (350-450 g) rats SAH was induced by transclival puncture of the basilar artery. Mean arterial blood pressure (MABP), LCBF, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured in all rats for 30 min before and 60 min after SAH was induced. One set of control (n : 7) and experimental animals (n : 7) was sacrificed after the 60 min of initial post-hemorrhage measurements were recorded. Four days after SAH induction, LCBF and MABP were measured again for 60 min in subgroups of surviving experimental rats (n : 7) and control rats (n : 7). Histopathologic and morphologic examinations of the basilar artery were performed in each subgroup. There was a sharp drop in LCBF just after SAH was induced (55.50 +/- 11.46 mlLD/min/100 g and 16.1 +/- 3.6 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001). The flow then gradually increased but had not returned to pre-SAH values by 60 min (p < 0.05). At 4 days after SAH induction, although LCBF was lower than that observed in the control group and pre-SAH values, it was not significantly different from either of these flow rates (p > 0.05). ICP (baseline 7.05 +/- 0.4 mmHg) increased acutely to 75.2 +/- 7.1 mmHg, but returned to normal levels by 60 min after SAH. CPP (baseline 84.5 +/- 6.3 mmHg) dropped accordingly (to 18.6 +/- 3.1 mmHg), and then increased, reaching 72.2 +/- 4.9 mmHg at 60 min after SAH (p > 0.05). Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer in the early stage. LCBF in nonsurviver rats (n : 8) was lower than that in the animals that survived (p < 0.01). At 4 days post-hemorrhage, the rats' basilar arteries showed marked vasculopathy. The findings showed that acute SAH alters LCBF, ICP, and CPP, and that decreased LCBF affects mortality rate. Subsequent vasculopathy occurs in delayed fashion, and this was observed at 4 days after the hemorrhage event. PMID- 11780776 TI - Effects of interrupted and uninterrupted occlusion of the basilar artery on cerebral blood flow, and on neurological and histological outcome in rats with subarachnoid hemorrhage. AB - Most neurosurgeons consider temporary vessel occlusion for aneurysmal clipping an effective technique that facilitates dissection between the aneurysm and the parent vessel. It is generally believed that repeated short periods of cerebral ischemia are safer for the brain than a single long episode. The aim of this study was to identify whether interrupted and uninterrupted vessel occlusion differs with regard to changes in brain tissue and cerebral hemodynamics after subarachnoid hemorrhage (SAH). Fifty Spraque Dawley rats (300-350 g) were placed under general anaesthesia and ventilated. The basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values was measured, and then the basilar artery was punctured, causing subarachnoid hemorrhage (SAH). Group I (n = 24) was subjected to 60 min of interrupted basilar artery occlusion, defined as 5 min of reperfusion after every 10 min of occlusion, group II (n = 26) 60 min of uninterrupted artery occlusion. Three days after completion of the experiment, each rat was neurologically evaluated and decapitated. Coronal brain slices were obtained and stained to assess infarct volume. Immediately after SAH, LCBF fell by 58% in group I, and by 52% in group II. In group I, each ischemic insult brought a similar reduction in LCBF, and after each release of the occlusion there was a rapid rise in flow. In group II, the LCBF values dropped initially and remained at low levels until the end of the study. The 2,3,5 triphenyltetrazolium chloride stained sections showed similar volumes of brainstem infarction in both groups (38.3 +/- 9.2 mm3 vs. 34.3 +/- 8.7 mm3, respectively; p > 0.05). The results suggest that there is no neuroprotective advantage to either interrupted or uninterrupted temporary blockage of blood flow during neurovascular procedures after SAH in the basilar artery region. PMID- 11780777 TI - Ischemic brain injury caused by interrupted versus uninterrupted occlusion in hypotensive rats with subarachnoid hemorrhage: neuroprotective effects of citicoline. AB - This study investigated the neuroprotection provided by cytidine 5' diphosphocholine (citicoline) during interrupted and uninterrupted occlusion of the basilar artery after subarachnoid hemorrhage (SAH) in 121 hypotensive rats. Animals were anesthetized and the basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values were recorded, and then the basilar artery was punctured, causing SAH. Blood was drawn to induce hypotension [60-70 mmHg mean arterial blood pressure (MABP)]. Control rats received intraperitoneal (i.p.) injections of 0.5 ml saline immediately after SAH before hypotension induction and after 60 min of occlusion. Experimental rats received 400-mg/kg citicoline i.p. at the same time points. Control group I and treatment group III were subjected to 60 min of interrupted occlusion (5 min of reperfusion after each 10 min of occlusion). Control group II and treatment group IV were subjected to 60 min of uninterrupted occlusion. MABP and LCBF were recorded every 5 minutes. Brain edema was evaluated in seven rats from each group at 24 hours after ischemic injury. At 3 days after occlusion, another set of 28 rats was killed and coronal brain slices were stained to assess infarct volume. The groups' physiological and edema findings were similar. In all groups, LCBF fell immediately after SAH and remained below baseline throughout the experiment. In the citicoline-treated rats, arterial pressure increased significantly after 30-40 min of occlusion, and brain slices showed significantly smaller infarct volumes compared to control slices (p < 0.05). Mortality was significantly lower in the citicoline-treated animals (p < 0.001). The results suggest that citicoline provides significant neuroprotection during cerebral ischemia, and that it significantly reduces mortality. Part of the neuroprotective effect may be mediated by recovery of arterial pressure. PMID- 11780778 TI - Absorption of a protein gavage in Zucker lean rats. Influence of protein content in the diet. AB - The rate of protein absorption was measured in Zucker lean rats. Rats were fed with a bolus that contained ca. 300 mg of 14C-labelled protein at the beginning of the light cycle. Blood was extracted from the portal vein at intervals up to 9 hours after gavage. Label incorporation into tissue protein was monitored. The digestion and absorption of protein was slow, and 9 hours after the gavage, 20% of the bolus remained in the stomach. Forty percent of the protein was absorbed in the first hour. This was followed first by a linear absorption process, then by the amino acid incorporation into tissue proteins. The appearance of label in the portal vein increased progressively for up to four hours, shifting to a progressive decrease that coincides with the maintenance of this label in the tissues. The skin, the striated muscle and the liver showed the highest amounts of labelled proteins. The application of this model to animals fed low-(LP) or high-protein (HP) content diets showed that the HP group digested the protein faster than the LP group, and that catabolism of the amino acids was higher in the HP group. The LP group digested protein much more slowly than the RD (control) group, but protein accretion was more efficient. PMID- 11780779 TI - Effects of vitamins and common drugs on reduction of 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone in rat microsomes. AB - 4-(Methylnitrosamino)-1-(3-pyridyl)-butanone (NNK) is a tobacco-specific nitrosamino that requires metabolic activation by cytochrome P450 enzymes. The activation of NNK by cytochrome P450 enzymes leads to the formation of different metabolites. Detoxification of NNK usually occurs via carbonyl reduction to its hydroxyl product, 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL). In the present study, the influences of common vitamins and P450 modulators on the reduction of NNK by rat microsomes were studied. The formation of NNAL but not other metabolites was detected by the described HPLC method. Among the vitamins tested, vitamins E, A (retinol), B6 and B5 were found to be marginal effective upon reduction of NNK while vitamins A (cis-acid), A (trans-acid), D2, D3, K1, K3, B1 and A (crocetin) increased the formation of NNAL from 3 to 21%. The effect of vitamin C-palmitate (<10 microM) was most pronounced followed by crocetin upon reduction of NNK. Clonidine, tolbutamide and atropine slightly increased the reduction of NNK while cimetidine showed no effects. The modulation of NNK reduction could reduce the carcinogenic potential of NNK, since the main detoxification pathway of NNK involves carbonyl reduction. PMID- 11780780 TI - Glycosylated rat prolactin: isolation and structural characterization. AB - Isolation of glycosylated 26 kDa rat prolactin and subsequent proper carbohydrate characterization has so far not been reported. In the present work the hormone isoform was isolated to 95% homogeneity by preparative electrophoretic separation on Mini Prep Cell of rat pituitary homogenate. The isoform was then investigated by 2-mercaptoethanol gradient electrophoresis, Cleveland's sequential SDS-PAGE, digestion with endoproteinase Asp-N and N-glycanase. The glycosidic part of the isoform was examined in O-profiling and its monosaccharide composition obtained by FACE and HPAE-PAD analysis. The outcome of the experimental data is: 1) in contrast to unglycosylated 23 kDa rat prolactin, intra-chain S-S bridging is not affected in 26kDa rat prolactin, neither by transiting through a thiol gradient nor in sequential nonreducing/reducing SDS-PAGE; 2) the conformational availability of Asp residues involved in the endoproteinase Asp-N attack is the same in 23- and 26 kDa rat prolactin; the glycan moiety apparently does not cause steric hindrance at this level; 3) no glycosidic N-linkage could be detected, only O-linkage(s); 4) 26 kDa rat prolactin is no glycosyl-phosphaditylinositol anchored protein; 5) in O-profiling an oligosaccharide chain of Mr +/- 1.4 kDa was recorded; 6) the monosaccharide composition obtained in FACE is peculiar in the sense that next to Fuc, Man, GalNac, GlcNac and NeuAc also Rib was determined; 7) HPAE-PAD analysis identified NeuAc subtypes; 8) in vitro, glycosylation of rat prolactin modulates immune recognition through steric hindrance of the access to the epitope sites. PMID- 11780781 TI - 'Rules of conduct': some practical guidelines for testing motor-nerve conduction. PMID- 11780782 TI - Myofascial force transmission causes interaction between adjacent muscles and connective tissue: effects of blunt dissection and compartmental fasciotomy on length force characteristics of rat extensor digitorum longus muscle. AB - Muscles within the anterior tibial compartment (extensor digitorum longus: EDL, tibialis anterior: TA, and extensor hallucis longus muscles: EHL) and within the peroneal compartment were excited simultaneously and maximally. The ankle joint was fixed kept at 90 degrees. For EDL length force characteristics were determined. This was performed first with the anterior tibial compartment intact (1), and subsequently after: (2) blunt dissection of the anterior and lateral interface of EDL and TA. (3) Full longitudinal lateral fasciotomy of the anterior tibial compartment. (4) Full removal of TA and EHL muscles. Length-force characteristics were changed significantly by these interventions. Blunt dissection caused a force decrease of approximately 10% at all lengths, i.e., without changing EDL optimum or active slack lengths. This indicates that intermuscular connective tissue mediates significant interactions between adjacent muscles. Indications of its relatively stiff mechanical properties were found both in the physiological part of the present study, as well as the anatomical survey of connective tissue. Full lateral compartmental fasciotomy increased optimum length and decreased active slack length, leading to an increase of length range (by approximately 47%), while decreasing optimal force. As a consequence an increase in force for the lower length range was found. Such changes of length force characteristics are compatible with an increased distribution of fiber mean sarcomere length. On the basis of these results, it is concluded that extramuscular connective tissue has a sufficiently stiff connection to intramuscular connective tissue to be able to play a role in force transmission. Therefore, in addition to intramuscular myofascial force transmission, extramuscular force transmission has to be considered within intact compartments of limbs. A survey of connective tissue structures within the compartment indicated sheet-like neuro-vascular tracts to be major components of extramuscular connective tissue with connections to intramuscular connective tissue stroma. Removal of TA and EHL yielded yet another decrease of force (mean for optimal force approximately 10%). No significant changes of optimum and active slack lengths could be shown in this case. It is concluded that myofascial force transmission should be taken into account when considering muscular function and its coordination, and in clinical decisions regarding fasciotomy and repetitive strain injury. PMID- 11780783 TI - Disclosure of new and recurrent microbial metabolites by mass spectrometric methods. AB - The application of modern mass spectrometry methods (SI-CID-MS/MS; MSn) in the disclosure of new and recurrent microbial metabolites is discussed. Spray ion (SI) sources coupled to different kinds of mass analyzers enable the determination of molecular weights and chemical formulas of given samples even in mixtures. Diagnostic fragment formation by collision-induced dissociation (CID MS/MS) and MSn experiments using ion trap mass analyzers are shown as another indispensable source of structural information. Due to the development of benchtop-type mass spectrometers coupled to high-performance liquid chromatography (HPLC), MS can be practised in almost every laboratory as a powerful tool in natural product analysis. Examples are given for special MS applications in identification of bioactive metabolites from screening strains. PMID- 11780784 TI - Simocyclinones: diversity of metabolites is dependent on fermentation conditions. AB - Simocyclinones, a novel group of angucyclinone antibiotics, are produced by Streptomyces antibioticus Tu 6040. The compounds show antibacterial and antitumor properties. In submerged cultivation, the production of simocyclinones is strongly dependent on the carbon and nitrogen sources used in a chemically defined medium. Productivity of distinct components and diversity of simocyclinone compounds are influenced by the medium composition. Four series of simocyclinone compounds were detected by high-performance liquid chromatography (HPLC) diode array detector (DAD) and HPLC electrospray ionization (ESI) mass spectrometry (MS) analysis, isolated and the structures determined by nuclear magnetic resonance (NMR) techniques. Under optimized conditions, simocyclinone D8 was produced in an amount of 300 mg l(-1) and simocyclinone C4 in a concentration up to 50 mg l(-1). PMID- 11780785 TI - Myxobacteria, producers of novel bioactive substances. AB - Myxobacteria are soil bacteria that move by gliding and have an astonishing life cycle culminating in fruiting body formation. In a research program at the Gesellshaft fur Biotechnologische Forschung over the past 25 years the organisms have been shown to be a rich source of potentially useful secondary metabolites. So far about 80 different basic compounds and 450 structural variants have been characterized. Many of those compounds were new. It is particularly remarkable that myxobacteria specialize in mechanisms of action that are very rare with other producers. Thus 20 new electron transport inhibitors, 10 substances that act on the cytoskeleton, four inhibitors of nucleic acid polymerases, and one inhibitor of fungal acetyl-CoA carboxylase, a novel mechanism of action, have been found. PMID- 11780786 TI - Chemical diversity in lipopeptide antifungal antibiotics. AB - In the course of screening for antifungal antibiotics, we have discovered a novel series of lipopeptide compounds structurally related to, but highly superior to, echinocandin B in terms of their water solubility due to the presence of a sulfate residue. These compounds, WF11899s, WF738s, WF14573s, WF16616 and WF22210, and their derivatives have diversity in their nuclear structures and acyl side chains. The producing strains were classified into two groups, the Coleomycetes group and the Hyphomycetes group. Compound FK463, a derivative of WF11899A, is currently in Phase 3 clinical development as a novel antifungal antibiotic. PMID- 11780787 TI - Cross-genomic analysis of the translational systems of various organisms. AB - We have characterized the genes encoding ribosomal proteins (r-proteins) as well as other translation-related factors of 15 eubacteria and four archaebacteria, and the genes for the mitochondrial r-proteins of Saccharomyces cerevisiae by using the complete genomic nucleotide sequence data of these organisms. In eubacteria, including two species of Mycoplasma, the operon structure of the r protein genes is well conserved, while their relative orientation and chromosomal location are quite divergent. The operon structure of the r-protein genes in archaebacteria, on the other hand, is quite different from eubacteria and also among themselves. In addition, many archaebacterial r-proteins show similarity to rat cytoplasmic r-proteins. Nonetheless, characteristic features of several genes encoding proteins of functional importance are well conserved throughout the bacterial species including archaebacteria, as well as in S. cerevisiae. We searched for the genes encoding mitochondrial r-proteins in yeast by combining informatics and genetic experiments. Furthermore, we characterized some of the r proteins genes by exchanging portions between Escherichia coli and S. cerevisiae and performed functional analysis of some of the genes from different evolutionary points of view. Our work may be extended towards phylogenetic analysis of organisms producing secondary metabolites of various sorts. PMID- 11780788 TI - Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases. AB - The analysis of the incorporation of 13C-labeled precursors into avermectins indicates that the avermectin aglycons are synthesized by head-to-tail condensation of various acyl groups, which is similar to the biosynthesis of other polyketides. Polyketide synthases (PKS) use the appropriate CoA ester as a primer and add acetate units from malonyl-CoA and propionate units from methylmalonyl-CoA to assemble the polyketides. Avermectin aglycons are formed by addition to the starter unit (2-methylbutyrate or isobutyrate) of 12 acyl condensations in the order P-A-A-A-A-P-P-A-P-A-P-A (P, propionyl; A, acetyl). Within the 90-kb gene cluster for a vermectin biosynthesis, the central 65-kb segment was found to be required for aglycon biosynthesis by phenotypic analysis of strains containing deletion or insertion mutations in this region. A complete sequence analysis of the 65-kb segment indicated that this segment encodes avermectin PKS. The avermectin PKS genes are organized into two converging blocks of ORFs. From the results of sequencing analysis, a feature of the two regions, aveA1/aveA2 and avea3/aveA4, is that they encode four kinds of large multifunctional polypeptides containing 55 domains which possess putative fatty acid synthase-like activities. The avermectin PKS (AVES 1-4) appear to contain two, three, or four modules. AVES1 and 2 contain two and four modules, respectively, whereas AVES 3 and AVES 4 each contains three modules. The 12 modules correspond to the 12 cycles required for synthesis of the avermectin aglycon. PMID- 11780789 TI - The A-factor regulatory cascade and cAMP in the regulation of physiological and morphological development in Streptomyces griseus. AB - In the A-factor regulatory cascade leading to the onset of streptomycin biosynthesis and aerial mycelium formation in Streptomyces griseus, the A-factor receptor protein (ArpA) serves as a DNA-binding repressor and A-factor releases the repression by binding to ArpA and dissociating it from the DNA. Mutants defective in arpA therefore produce streptomycin and aerial hyphae in the absence of A-factor. A gene that inhibits streptomycin production and aerial hyphae formation in an arpA mutant was cloned on a high-copy-number plasmid and found to encode a eukaryotic-type adenylate cyclase (CyaA). Consistent with this, an exogenous supply of cAMP at high concentration almost abolished streptomycin production and aerial hyphae formation. On the other hand, cAMP at lower concentrations stimulated or accelerated these developmental processes. The effects of cAMP were detectable only in arpA mutants, and not in the wild -type strain; an exogenous supply of cAMP or cyaA disruption in the wild-type strain caused almost no effect on these phenotypes. Thus the effects of cAMP became apparent only in the arpA-defective background. cAMP at high concentrations inhibited stringent response factor ppGpp production, which is important for the onset of antibiotic biosynthesis. cAMP also influenced the timing of tyrosine phosphorylation of more than nine proteins. These findings show that a cAMP regulatory relay for physiological and morphological development functions in a concerted and interdependent way with other signal transduction pathways. PMID- 11780790 TI - Antibiotic biosynthesis: from natural to unnatural compounds. AB - The evolution of the field of biosynthesis from the unravelling of the mode of formation of natural products to the use of such knowledge to create new compounds is reviewed using examples from the author's laboratory. The discussion focuses on the mode of operation of type II (spore pigment PKS) and type I (rifamycin PKS) polyketide synthases and their diversion to generate unnatural products, and on the genetics and biochemistry of deoxysugar formation in granaticin biosynthesis as a prerequisite to combinatorial enzymatic synthesis of unusual glycosides. PMID- 11780791 TI - The CBT of delusional disorder: the relationship between schema vulnerability and psychotic content. AB - This paper reports the process, interventions, and outcome of the cognitive behavioural therapy of a patient who had a diagnosis of delusional disorder. The clinical features, process of therapy, and successful outcome are all discussed in relation to explanatory information processing models of delusion development and maintenance, and recent developments in formulation-driven CBT of delusions. The implications for therapy, service development, and training are discussed. Beliefs that mediate the relationship between core schemas and delusions may form a helpful focus for early therapeutic endeavour in psychosis. PMID- 11780792 TI - OCD patients and non-patient groups reporting obsessions and compulsions: phenomenology, help-seeking, and access to treatment. AB - This article offers a preliminary examination of factors that may be important to seeking help and receiving treatment for obsessive-compulsive symptoms. Community studies typically reveal individuals who display significant obsessive-compulsive symptomatology. Such individuals are often used in analogue research that attempts to understand various symptom dimensions and associated characteristics relevant to clinical obsessional states. This article questions why, if these non patient groups are sufficiently similar to patients in terms of phenomenology, there should exist a disparity in treatment status. This question is addressed in the following way: first, obsessive-compulsive symptoms and associated features that may be central to help-seeking are considered in both patient and non patient groups. A central argument in this part of the article is that cross study phenomenological comparisons are hindered by diversity in research selection criteria. Secondly, general factors that may be considered important to help-seeking for psychological distress are considered, as too are those factors that may be applied to the consideration of help-seeking for obsessive-compulsive problems specifically. Finally, the implications of these issues in the literature for research and clinical practice are considered. PMID- 11780793 TI - The role of shame and guilt in traumatic events: a clinical model of shame-based and guilt-based PTSD. AB - Post-traumatic stress disorder is currently classified as an anxiety disorder with fear as the predominant emotion. This has led to the development of treatment techniques such as exposure aimed at alleviating fear. This article highlights the need to address other emotional responses, in particular shame and guilt, when assessing and treating PTSD. Hence, it presents two clinical models of shame-based PTSD and guilt-based PTSD. These models are offered as aids to clinicians in assessing and formulating cases of PTSD where shame and guilt are salient issues. The models highlight the importance of assessing meaning in the context of pre-existing schemas and address two pathways to the development of shame and/or guilt: schema congruence and schema incongruence. Several treatment implications are drawn from the models. PMID- 11780794 TI - The effect of dissociation at encoding on intrusive memories for a stressful film. AB - The occurrence of memory intrusions after a trauma has been linked to peri traumatic dissociation. In this study, we attempted to induce dissociation experimentally and investigate the impact on intrusive memories. A total of 39 undergraduates were randomly assigned to watch a stressful film under standard conditions or under a dual-task condition in which they simultaneously performed a tapping task. They rated their distress post-film and again after 2 weeks, and kept a diary of intrusive memories. Contrary to prediction, there were no differences in levels of distress or explicit memory between the two conditions, and the dual-task condition was followed by significantly fewer memory intrusions. Dual-task conditions may not provide a good analogue to naturally occurring dissociation. The possible preventive effects of the tapping task are discussed in terms of the dual-representation theory of post-traumatic stress disorder. PMID- 11780795 TI - Mediation of depression by perceptions of defeat and entrapment in high-stress mothers. AB - Previous studies have demonstrated a causal role of stress in depression, and an association between depression and perceptions of defeat and entrapment. The present study was conducted to determine whether perceptions of defeat/entrapment mediate the relationship between stress and depression. Seventy-six mothers of children attending specialist educational provision for a range of special needs completed the Parenting Stress Index-Short Form (PSI-SF), Defeat and Entrapment Scales, the Beck Depression Inventory (BDI), and the Fawcett-Clark Pleasure Capacity Scale (FCPCS). Relative to population norms, respondents reported very high levels of stress, moderately high levels of defeat/entrapment, mild depression, and very low hedonic capacities. Most of these measures were more extreme in younger mothers and those with a prior history of depression. FCPCS scores were correlated negatively with stress, after controlling for levels of defeat/entrapment, but were not correlated with BDI scores, suggesting that the FCPCS may be an unsuitable instrument for use in the present participant population. Significant positive correlations were found between all measures of stress, defeat/entrapment and depression. After controlling for PSI-SF scores, correlations between BDI and defeat/entrapment scores remained highly significant. However, after controlling for defeat/entrapment, correlations between BDI and PSI-SF scores were non-significant. Hence, perceptions of defeat/entrapment mediate the relationship between stress and depression. This relationship was confirmed formally using regression analysis. Because respondents reported high levels of stress in contrast to mild levels of depression, a causal link can be inferred, running from stress via defeat/entrapment to depression. PMID- 11780796 TI - Affective states associated with bingeing and purging behaviours in Japanese patients with bulimia nervosa. AB - This study investigated the relationship between binge-purge episodes and the affective state by analysing the changes in affective states during the binge purge cycle. Thirty-seven Japanese patients with bulimia nervosa were surveyed for 22 types of affective states. Some negative affects were alleviated by bingeing or purging, while others were exacerbated by these behaviours. These findings suggest that one has to differentiate the temporal situations in the binge-purge cycle in considering the relationship between the affective states and binge-purge behaviours. The escape hypothesis and hopelessness hypothesis proposed by Beebe (1994) suggest some possible mechanisms. Binge and purge behaviours should be examined separately as defence functions to regulate negative moods and as acting out in response to intense negative affects. PMID- 11780797 TI - Attachment in anorexia nervosa: a transgenerational perspective. AB - Both clinical and empirical studies suggest that insecure attachment is common in eating disordered populations. Clinical studies have addressed mother-daughter interactions, but there has been little empirical research into the mother's own attachment patterns and whether there might be intergenerational transmission of these patterns. We aimed to examine the attachment status of patients with severe anorexia nervosa and their mothers, using the 'gold standard' Adult Attachment Interview (AAI). We predicted: (1) a high level of insecurity among the patients (women with anorexia nervosa with or without bulimic behaviours); (2) that the mothers would show a higher rate of insecurity than predicted by population norms; and (3) that there might be attachment style associations within mother daughter pairs. Twenty consecutive in-patients with a DSM-IV diagnosis of anorexia nervosa were interviewed using the AAI, as were 12 of their mothers. The mental state of daughters was rated by experienced clinicians, and that of mothers by the Clinical Interview Schedule (Revised). AAIs were transcribed and rated by expert raters. Nineteen (95%) daughters and 10 (83%) mothers were rated insecure on the AAI. Of these, 15 (79%) daughters and seven (70%) mothers were dismissive in type. We did not find an association between mothers' and daughters' attachment style. The incidence of unresolved loss was high among the mothers (67%). Idealization scores were high and reflective functioning scores low in both mother and daughter groups. Women with anorexia nervosa and their mothers commonly have a dismissive attachment style. Low levels of reflective functioning and high idealization scores are found in both groups, and may be learned (or transmitted) from mother to daughter. A difficulty in emotional processing, exemplified by unresolved loss, may be transmitted to daughters, and act as a risk factor for the development of anorexia nervosa. PMID- 11780798 TI - Body experience and mental representation of body image in patients with haematological malignancies and cancer as assessed with the Body Grid. AB - The domain of body image plays a central role in the quality of life of patients with haematological malignancies and metastasized cancer, since the disease itself as well as the enrolled therapies interfere with psychological and bodily well-being. We approached this highly subjective field by using the repertory grid technique and hypothesized that patients would display a restricted body image, focusing on functional aspects of the body. In all, 55 in-patients (27 men, 28 women, M age = 45.7 yrs, N = 46 with haematological malignancies, N = 9 with metastasized cancer), at the time of initial diagnosis, were included in the study and assessed with the Body Grid, an instrument specifically designed by us for the exploration of body image. The data were analysed by principal component analysis (PCA) and construct categorization. Further, 42 chronic tinnitus sufferers (20 male, 22 female, M age = 46.5 yrs) served as a comparison group. Based on the constructs elicited, six construct categories were formulated in the sense of a first attempt of a hierarchical model (emotion, control, activity, strength, function, appearance). The central constructs (373 construct pairs) were assigned to these categories by three inter-raters. The categories appeared in the following order of frequency: function (27.1%), emotion (20.4%), strength (20.1%), activity (15%), control (10.2%) and appearance (7.2%). PCA indicated that the patients mainly demonstrated a restricted view of their body. In the tinnitus group, the most frequent category proved to be activity (21.3%), closely followed by function (21.1%) and control (20.9%). The body image was also restricted (PCA). The restriction of body image, together with the specific construct choice, seen in the haematology and cancer patients reflects the existential threat of the disease and may serve as a coping strategy. The high percentage of emotional constructs may mirror the patients' need for further support. The distinct distribution of construct categories in the two different patient samples supports the applicability of the proposed preliminary model. PMID- 11780799 TI - Fatigue and patterns of pain in fibromyalgia: correlations with anxiety, depression and co-morbidity in a female county sample. AB - This study explored the prevalence of fibromyalgia, the relationship of anxiety and depression with two major symptoms (pain and fatigue), and the role of co morbidity. Participants were recruited from the Nord-Trondelag Health Study (The HUNT Study) in Norway (N = 92,936). They were females given the diagnosis of fibromyalgia by their doctor (N = 1,816), divided into one sample without (N = 977) and another with (N = 839) co-morbidity. Owing to colinearity between anxiety and depression, extreme groups were defined according to high vs. low anxiety and depression scores. About four-fifths of the initial sample were excluded by this approach, which permitted a two x two factorial split-plot ANCOVA for the assessment of the relations of anxiety and depression with pain and fatigue. The overall prevalence was 3.2%, which obscured a highly biased sex difference with 5.2% for females and .9% for males. Results from the sample without co-morbidity (N = 977) supported the idea of independent partial correlations of anxiety and depression with pain and fatigue. A different trend was indicated in the co-morbidity sample (N = 839) where fatigue was only significantly associated with depression, whereas pain was associated with anxiety. The idea of widespread pain was supported consistently only in participants without co-morbidity who scored low on anxiety. Age, incident pain and depression contributed to a discriminant function reflecting the status of co morbidity. PMID- 11780800 TI - Existential loneliness: a review of the concept, its psychosocial precipitants and psychotherapeutic implications for HIV-infected women. AB - While many of the most urgent psychological issues that women with HIV infection are forced to deal with are existential in nature, and therefore shared by humankind, the assault on their physical and psychological being may trigger these issues in large amounts and may overwhelm their defensive structure. Existential loneliness may be an important existential issue that arises for these women and needs to be given equal consideration alongside other forms of loneliness. In this paper, we review the concept of existential loneliness, discuss methods to measure the concept, delineate some central psychosocial precipitants of existential loneliness among HIV-infected women, and discuss psychotherapeutic implications. We conclude that incorporating an existential philosophical perspective into one's particular therapeutic stance may be especially appropriate with this population. PMID- 11780801 TI - Introduction of David J. Marcogliese as the Henry Baldwin Ward Medalist for 2001. PMID- 11780802 TI - Acceptance of the 2001 Henry Baldwin Ward Medal. PMID- 11780803 TI - Introduction of Dr. Brent B. Nickol, recipient of the Clark P. Read Mentor Award. PMID- 11780804 TI - Acceptance of the Clark P. Read Mentor Award: what makes a mentor? PMID- 11780805 TI - Presentation of the ASP Distinguished Service Award to Robert L. Rausch. American Society of Parasitologists. PMID- 11780806 TI - Lipid and protein composition at different developmental stages of Pediculus capitis (Arthropoda, Phthiraptera). AB - Protein and lipid compositions were studied at different developmental stages of Pediculus capitis De Geer 1778. Phosphatidylcholine was found to be the predominant lipid at all stages and in both sexes. Palmitic and oleic acids were the main fatty acids throughout the 3 stages studied. A marked decline was observed in the total lipid content and triacylglyceride concentration during development, suggesting that their consumption is an energy source. The electrophoretic mobility revealed the predominance of a 320-kDa protein in eggs and adult females, whereas 2 major proteins of 514 and 439 kDa were found in nymphs, as well as in male and female adults. Two very high density lipoprotein fractions were isolated by ultracentrifugation of egg cytosol in a density gradient of NaBr. Both reserve lipoproteins contained phospholipids and triacylglycerols as the predominant lipids and a protein band of around 320 kDa. The structure of this band is likely to be similar to that found in females in a vitellogenic state. PMID- 11780807 TI - Myoelectric response of the small intestine to the orad presence of the tapeworm Hymenolepis diminuta. AB - During its 24-hr migratory cycle in the small intestine, Hymenolepis diminuta is located in the orad part of the small intestine during the early morning hours and then in the caudad part of the small intestine during the late afternoon and early evening. During the later period, tapeworm-induced alterations of interdigestive myoelectric activity, a correlate of smooth muscle contraction or intestinal motility, are most intense in the ileal region. The hypothesis tested was that the tapeworm-induced changes in intestinal motility are local responses of the intestine responding to the close proximity of the lumenally positioned tapeworm and to the nutritional state of the host. The small intestine was monitored before and for 20 days after infection using electrodes implanted on the serosa of the small intestine. Myoelectric recordings were analyzed for the frequency of the normal patterns of interdigestive myoelectric spiking patterns and the altered myoelectric spiking related to tapeworm infection. During the morning hours, when the tapeworms are situated in the orad small intestine, no changes were observed during the normal myoelectric pattern of the digestive phase in any region of the intestine. When examined after the conversion of the digestive to interdigestive phase of motility, only on day 10 postinfection was the interdigestive phase significantly altered. It was concluded that the presence of the tapeworm in the orad small intestine during the satiety stage of the rat causes no changes in the electric events of the small intestine, with the exception of day 10 postinfection. Because tapeworms in the orad small intestine do not induce the tapeworm-altered myoelectric activity observed in the afternoon and evening with caudally positioned tapeworms, tapeworm-altered motility is not simply a response of the small intestine to the local presence of the tapeworm. PMID- 11780808 TI - Modulation of caudal intestinal permeability in the rat during infection by the tapeworm Hymenolepis diminuta. AB - Bidirectional movement of solutes between the intestinal lumen and systemic circulation is restricted by tissue barriers that may be altered under conditions such as intestinal infection. In a study using an in vitro everted sac preparation to assess small intestinal permeability in a lumen-to-serosa direction, 51Cr-EDTA movement was compared regionally in the jejunum and ileum of rats infected and uninfected by tapeworms. Whereas jejunal segments showed no significant differences in permeability to 51Cr-EDTA at 6, 15, or 32 days postinfection (dpi), ileal segments displayed an increased permeability on 15 and 32 dpi, but not 6 dpi. The alterations in permeability were not reversed 1 wk after removal of the tapeworm from the intestine. In conclusion, the strictly lumen-dwelling tapeworm infection allows increased movement of molecules from the lumen into ileal, but not jejunal, tissues by 15 dpi. PMID- 11780809 TI - Development of Onchocerca volvulus (Filarioidea: Onchocercidae) in the West African black fly Simulium yahense (Diptera: Simuliidae) in Liberia. AB - Simulium yahense black flies infected with microfilaria of Onchocerca volvulus were kept in a defined insectary environment in Liberia, West Africa. A daily sample of infected flies was dissected for larvae developing in the thoracic muscles and examined for growth in stadial development. Microfilariae ingested by black flies transformed to the L1 larval stage without molting. Successive larval development included molting to the L2 stage and, finally, to the L3 stage, which was infective in humans. The cephalic cap, consisting of a laterally located hook and central stoma, occurs in the first larval stage. The caudal appendix and the laterally located anal opening are apparent in the L1 larva. In the L2 stage, the cephalic cap is lost and the large circular stoma becomes surrounded with elevated flaps. The caudal appendix was lost after larvae molted to the L3 stage, and in its place, 3 terminal papillae developed. Sense organs, such as 2 opposing phasmids and 8 papillae that were arranged into 2 circles, developed in the cephalic region of the L3 larva. The evidence of pathological consequences due to the presence of the L3 larva in the fly host are illustrated and discussed. PMID- 11780810 TI - The guest playing host: colonization of the introduced Mediterranean gecko, Hemidactylus turcicus, by helminth parasites in southeastern Louisiana. AB - Parasite surveys of exotic hosts offer the opportunity to examine parasite colonization on different scales (i.e., host individual, host population, host species, and new geographic locality). Ten helminths (Macracanthorhynchus ingens, Mesocestoides lineatus, Oochoristica javaensis, Haematoloechus varioplexus, Mesocoelium monas, Telorchis corti, Cosmocercoides variabilis, Oswaldocruzia leidyi, Skrjabinoptera sp., and a larval acuariid nematode) were recovered from the exotic Mediterranean gecko Hemidactylus turcicus, in southeastern Louisiana. Only 1 exotic parasite, O. javaensis, colonized a new geographic locality, but 7 local helminths colonized a new host species. Helminth communities of H. turcicus were similar in structure to what has been hypothesized or observed for lizards. Thus, communities were composed of generalists and were depauperate (i.e., colonization of individual geckos or host populations was rare for most of the helminths); however, there was significant variation in community structure among local habitats. Although the gecko's behavioral and physiological attributes predict colonization by monoxenous helminths, only 2, C. variabilis and O. leidyi, were recovered. Eight heteroxenous helminths, 2 of which (the acuariid and O. javaensis) were the most widely distributed and abundant, were the better colonizers. The gecko's generalist diet may have exposed it to a diverse parasite fauna and thus been important in determining the helminths that could colonize. PMID- 11780811 TI - Kroeyerina deetsorum n. sp. (Copepoda: Kroyeriidae) from the olfactory sacs of Atlantic sharpnose sharks (Rhizoprionodon terraenovae) captured in the Gulf of Mexico and northwestern Atlantic and first report of copepodids representing Kroyeriidae. AB - Kroeyerina deetsorum n. sp. (Copepoda: Kroyeriidae) is described from female and male specimens collected from the olfactory sacs of Atlantic sharpnose sharks, Rhizoprionodon terraenovae (Richardson, 1836), captured in the Gulf of Mexico and northwestern Atlantic. Kroeyerina deetsorum is easily distinguished from known congeners by the extremely small size of its adults (i.e., females about 1.2 mm total length and males about 1.0 mm total length). Kroeyerina deetsorum is also distinguished from its congeners by possessing a subquadrate rostrum without lobes or upturned horns. It is suspected that K. deetsorum belongs to a clade within Kroeyerina whose members only infect sharks. This report also provides first descriptions of a nauplius representing Kroeyerina and copepodids representing Kroyeriidae. The early-stage copepodid of K. deetsorum lacks a frontal organ and frontal filament and uses its chelate antennae to attach to its host. PMID- 11780812 TI - Critical evaluation of five methods for quantifying chewing lice (Insecta: Phthiraptera). AB - Five methods for estimating the abundance of chewing lice (Insecta: Phthiraptera) were tested. To evaluate the methods, feral pigeons (Columba livia) and 2 species of ischnoceran lice were used. The fraction of lice removed by each method was compared, and least squares linear regression was used to determine how well each method predicted total abundance. Total abundance was assessed in most cases using KOH dissolution. The 2 methods involving dead birds (body washing and post mortem-ruffling) provided better results than 3 methods involving live birds (dust-ruffling, fumigation chambers, and visual examination). Body washing removed the largest fraction of lice (>82%) and was an extremely accurate predictor of total abundance (r2 = 0.99). Post-mortem-ruffling was also an accurate predictor of total abundance (r2 > or = 0.88), even though it removed a smaller proportion of lice (<70%) than body washing. Dust-ruffling and fumigation chambers removed even fewer lice, but were still reasonably accurate predictors of total abundance, except in the case of data sets restricted to birds with relatively few lice. Visual examination, the only method not requiring that lice be removed from the host, was an accurate predictor of louse abundance, except in the case of wing lice on lightly parasitized birds. PMID- 11780813 TI - Prevalence and abundance of Ixodes pacificus immatures (Acari: Ixodidae) infesting western fence lizards (Sceloporus occidentalis) in northern California: temporal trends and environmental correlates. AB - The prevalence and abundance of immature Ixodes pacificus ticks on western fence lizards (Sceloporus occidentalis) were examined in relation to time of year, host attributes (i.e., age, gender, and presence or absence of blood parasites), and 5 environmental characteristics, including topographic exposure and ground cover substrate, over a 2-year period in northern California. Lizards were infested with subadult ticks from early March until late July or early August, with peak median numbers of larvae and nymphs recorded in late April and early May of both years. Peak larval and nymphal abundances differed between years. The overall ratio of larvae to nymphs on adult male lizards was low, ranging from 0.80 in 1999 to 2.41 in 2000. Such intensive feeding of nymphs versus larvae on these lizards, which are reservoir-incompetent for Borrelia burgdorferi spirochetes, may explain previous observations of decreasing spirochetal infection prevalence from the nymphal to adult stage in northwestern California. Adult male lizards were more likely to be infested with nymphs and harbored greater abundances of larvae and nymphs than adult females. Lizards uninfected with blood parasites had more nymphs than infected lizards. The measured environmental characteristics could explain only a small percentage of the total variation observed in larval prevalence (22%) and in larval and nymphal abundance (12 and 3%, respectively). PMID- 11780814 TI - Effect of sex, size, and age of commensal rat hosts on the infestation parameters of their ectoparasites in a rural area of Egypt. AB - The present study was carried out in the Bilbeis area, Sharqiya Governorate, Egypt. A total of 127 male and 115 female black rats Rattus rattus and 124 male and 153 female Norway rats R. norvegicus was collected during the study period. A total of 20,643 and 40,997 ectoparasites was recovered from R. rattus and R. norvegicus, respectively. Three common mite species were recovered from both rat hosts: Ornithonyssus bacoti, Radfordia ensifera, and Laelaps nuttalli. Three common flea species were also recovered from both rat hosts: Echidnophaga gallinacea, Leptopsylla segnis, and Xenopsylla cheopis. Polyplax spinulosa was the only louse species that infested both rat hosts. Rats that lived more than 12 mo formed about 24 and 14% of the populations of the black and Norway rats, respectively. The prevalences and general indices of many ectoparasites were significantly higher on males than on females of both rat hosts. Seasonal differences in prevalences and general indices of many ectoparasites were recorded between the 2 sexes of both rat species. Prevalences and general indices of most ectoparasites on both rat species showed a tendency to increase with increasing size and age of rat hosts. The type and degree of correlation between prevalences and general indices on the one hand and each of body size and age on the other hand differed among the species of ectoparasites. PMID- 11780815 TI - Neural sarcocystosis in a straw-necked ibis (Carphibis spinicollis) associated with a Sarcocystis neurona-like organism and description of muscular sarcocysts of an unidentified Sarcocystis species. AB - A Sarcocystis neurona-like parasite was associated with acute sarcocystosis in the brain of an ibis (Carphibis spinicollis). Numerous schizonts and merozoites were found extravascularly in encephalitic lesions. These schizonts reacted positively with anti-S. neurona and anti-S. falcatula polyclonal antibodies in an immunohistochemical test. Sarcocysts of an unidentified Sarcocystis species were present in the brain, heart, and skeletal muscles. Sarcocysts in skeletal muscles were microscopic, and the sarcocyst wall was up to 3 microm thick. The villar protrusions on the sarcocyst wall were up to 4.5 microm long, constricted at the base, and expanded laterally. Schizonts and sarcocysts distinct from those of S. falcatula. PMID- 11780816 TI - Structure of Sarcocystis neurona sarcocysts. AB - The ultrastructure of Sarcocystis neurona sarcocysts was studied from muscle of an experimentally infected cat. The cat was killed 144 days after being fed sporocysts from a naturally infected opossum. Sarcocysts were microscopic, up to 700 microm long, and up to 50 microm wide. By light microscopy, the sarcocyst wall was 1-2 microm thick. Ultrastructurally, the sarcocyst wall consisted of numerous villar protrusions. The villar protrusions were up to 2.8 microm long and 0.4 microm wide, with a tapered end. Microtubules extended from the tip of the villus to the base and occasionally extended deep into the granular layer. The granular layer was approximately 0.5 microm thick. Longitudinally cut bradyzoites were 5.2 by 1.2 (4.8-6.5 by 1.0-1.3) microm in size. Micronemes in bradyzoites were numerous and located in the anterior 1/3 of the conoidal end. PMID- 11780817 TI - Monticellia ophisterni n. sp. (Cestoda: Monticelliidae) from the swamp-eel Ophisternon aenigmaticum (Synbranchiformes) from Mexico. AB - Monticellia ophisterni n. sp. is described from the swamp-eel Ophisternon aenigmaticum Rosen and Greenwood (Synbranchiformes: Synbranchidae) from Lake Catemaco, Veracruz, Mexico. The new species is placed into Monticellia because of the cortical position of the testes, ovary, and uterus. It differs from other Monticellia species (with the exception of Monticellia magna (Rego, Santos and Silva, 1974)) in the position of longitudinal musculature that crosses the vitelline follicles, making them paramuscular. The new species can be distinguished from M. magna--which possesses a similar number of testes (107 139), paramuscular vitelline follicles, and numerous gland cells distributed between the apex of the scolex and suckers--in the position of the genital pore (8-21% vs. 19-27%), in the presence of a weak internal longitudinal musculature, in the arrangement of the testes in the median field, and in the absence of a vaginal sphincter. This is the first proteocephalidean tapeworm reported from a synbranchid fish and the first species of Monticellia found in North America. PMID- 11780818 TI - Genetic variability of trypanosomatids isolated from phytophagous hemiptera defined by morphological, biochemical, and molecular taxonomic markers. AB - In the present study, we investigated the genetic variability among 49 new isolates of trypanosomatids from phytophagous Hemiptera by means of morphological characters, growth features, and biochemical (enzymes of ornithine-arginine cycle) and molecular markers (based on spliced-leader, and ribosomal genes). From 402 phytophagous insects dissected and examined for the presence of trypanosomatids, 228 species belonging to Pyrrhocoridae, Coreidae, Lygaeidae, and Pentatomidae families harbored trypanosomatids in their salivary glands, or digestive tubes. Among these insects, 211 carried promastigotes and only 17 had choanomastigote forms. The results show a strong association among morphology, growth features, and biochemical and molecular markers and reveal the genetic diversity of the isolates, which were assigned to Crithidia, Phytomonas, and Leptomonas; we found genetic polymorphism within all these genera, thus indicating high genetic variability among trypanosomatids from phytophagous insects. PMID- 11780819 TI - Salivary gland extract from Ixodes ricinus tick polarizes the cytokine profile toward Th2 and suppresses proliferation of T lymphocytes in human PBMC culture. AB - Tick salivary gland extract (SGE) was previously shown to inhibit murine T cell proliferation. In mice, SGE has an inhibitory effect on Th1 and a stimulatory effect on Th2 cytokine elaboration. In the present study, tick-mediated immunomodulation of human T cell proliferation and cytokine elaboration was analyzed using human peripheral blood mononuclear cells (PBMCs) stimulated with concanavalin A (Con A) or lipopolysaccharide (LPS). Using flow cytometry, tick saliva-induced changes were investigated in human mononuclear cell subpopulations. SGE from Ixodes ricinus dose-dependently inhibited human T cell proliferation. This finding supports the flow cytometry data, showing that the percentage of Con A-activated HLA-DR-CD3+ T lymphocytes and CD4+ CD8+ double positive T cells decreased after SGE treatment. SGE significantly inhibited the in vitro production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) secreted by Th1 lymphocytes. In contrast, the elaboration of IL-4, IL-6, and IL 10 secreted by Th2 lymphocytes was significantly stimulated by I. ricinus SGE. Similarly, the production of both IL-1alpha and IL-1beta was significantly stimulated after SGE treatment. These data indicate that the tick-induced immunomodulatory events in humans are similar to those previously described in a murine model. PMID- 11780820 TI - Infection behavior of the rhabditid nematode Phasmarhabditis hermaphrodita to the grey garden slug Deroceras reticulatum. AB - Infection behavior of the rhabditid nematode Phasmarhabditis hermaphrodita to the grey garden slug Deroceras reticulatum was studied. The dauer (enduring or nonaging) juveniles of P. hermaphrodita invade D. reticulatum within 8-16 hr following external exposure, with the posterior mantle region containing the shell cavity serving as the main portal of entry. The dauer juveniles can recover, multiply, and produce new dauer juveniles in the slug and slug feces homogenates, but not in the soil extract. These results demonstrate that P. hermaphrodita is a facultative parasite of the slug and can complete its life cycle under nonparasitic conditions associated with the host. Although the juvenile and adult nematodes can kill the slug if injected into the shell cavity of the host, only the dauer juvenile can serve as an infective stage in the natural environment. PMID- 11780821 TI - Pathogenicity of entomopathogenic fungi to different developmental stages of Rhipicephalus sanguineus (Acari: Ixodidae). AB - The pathogenicity of 4 species of entomopathogenic fungi (Hyphomycetes species: Beauveria bassiana, Metarhizium anisopliae, Metarhizium flavoviride, and Paecilomyces fumosoroseus) to various developmental stages of Rhipicephalus sanguineus (Acari: Ixodidae) ticks was compared under laboratory conditions. The most virulent isolate, M. anisopliae-108, caused 92-96% mortality to unfed larvae and nymphs on day 7 postinfection (PI) and 100% mortality to unfed adults and engorged females on day 21 PI. The pathogenicity of M. anisopliae-108 to engorged larvae and nymphs was lower--82.6 and 60%, respectively. All tested B. bassiana, M. flavoviride, and P. fumosoroseus isolates were significantly less virulent (P < 0.05) or avirulent toward most life stages of R. sanguineus. The M. anisopliae and M. flavoviride isolates also prevented or reduced the ability of the ticks to lay eggs several days before their deaths. Female ticks infected by the fungi achieved only 11.3-60.8% of their egg-laying capacity compared with the controls. PMID- 11780823 TI - The swimbladder nematode Anguillicola crassus in American eels (Anguilla rostrata) from middle and upper regions of Chesapeake Bay. AB - The patterns of infection of American eels Anguilla rostrata, with the introduced swimbladder nematode Anguillicola crassus, in tributaries of middle and upper Chesapeake Bay are described. A total of 423 subadult eels was collected from 8 Bay tributaries from spring 1998 to fall 1999. Also, 30 elvers were collected from Ocean City, Maryland, in spring 1998. The numbers of juvenile and adult specimens of A. crassus in the swimbladder wall and lumen were counted. No elvers were infected. In subadult eels, prevalence of adult and juvenile stages combined ranged from 13% to 82%; mean intensity ranged from 2.6 to 9.0 worms per eel. Infection levels were highest for Susquehanna River eels (northernmost river) and lowest in the southernmost sites: St. Jerome's Creek and the Pocomoke River. Although eels from these 2 localities were larger, the low infection rates there are most likely due to reduced transmission in higher salinity water and not to eel size. Eels with both adult and juvenile stages of A. crassus were more common than expected by chance. This might be explained by inhibition of juveniles migrating into the swimbladder lumen when adults are already present there. PMID- 11780824 TI - Seasonal transmission of gastrointestinal parasites of equids in southern Louisiana. AB - Parasite-naive pony foals were used as sentinels to monitor transmission of gastrointestinal parasites of equids in Louisiana during 4 seasons of the year. Two annual periods were studied, 1988-1989 and 1992-1993. Two or 3 foals each season were turned out to graze a contaminated pasture along with resident parasitized mares and their foals. After a grazing period of 8 wk, sentinel ponies were held in a parasite-free box stall for a period of 6 wk to allow parasites to develop, thus enhancing the evaluation of hypobiotic stages. Following this holding period, necropsies were performed for complete parasite recoveries. Data show that transmission of large and small strongyles occurs during all seasons in southern Louisiana, with highest levels of transmission occurring in the winter and only minimal transmission taking place in the summer. Numbers of mucosal cyathostomes, as well as total cyathostome numbers, were highest in the winter, and luminal cyathostome numbers were highest in the spring. Transmission of Anoplocephala perfoliata and Parascaris equorum occurred during all seasons of the year, although numbers of P. equorum were reduced in spring 1989 and 1993. Gasterophilus intestinalis instars were recovered from fall and winter sentinels only. Oxyuris equi L4 were found all seasons 1 yr, but only during the fall and winter of the final year. PMID- 11780822 TI - Further characterization of passively transferred resistance to Schistosoma mansoni in the snail intermediate host Biomphalaria glabrata. AB - A heat-labile plasma factor from genetically resistant 10-R2 Biomphalaria glabrata snails confers passively transferred resistance (PTR) to Schistosoma mansoni when injected into susceptible snails within 24-hr of exposure to miracidia. However, no additional details on PTR have emerged since the initial 1984 report, nor has the plasma resistance factor been characterized. In the present study, new information is provided on the occurrence of resistance factor in plasma of additional types of snails, effect of "priming" resistant plasma donors by prior exposure to miracidia, duration of PTR, molecular weight of resistance factor, and fate of sporocysts in snails with PTR. Susceptible NIH albino snails injected 24 hr prior to exposure to miracidia with individual samples of plasma from a different strain (Salvador B. glabrata) or a different species (B. obstructa) of nonsusceptible snail displayed infection prevalences of 49% or 59% of control levels, respectively, whereas injections of homologous plasma had no effect. PTR was not enhanced by prior exposure of resistant Salvador plasma donors to miracidia. Unexpectedly, PTR induced by injections of Salvador plasma persisted for at least 21 days. The molecular weight of the resistance factor(s) was between 10 and 30 kDa, based on results of centrifugal ultrafiltration. A significantly higher proportion of dead sporocysts occurred in histological sections of tentacles from snails injected with Salvador plasma than in tentacles of snails injected with NIH albino plasma at 7 days postexposure to miracidia. Most dead sporocysts in Salvador plasma-injected snails were undergoing gradual degeneration, rather than rapid, hemocyte-mediated destruction, as occurred in Salvador snails. PMID- 11780825 TI - Host associations of ticks parasitizing rodents at Borrelia burgdorferi enzootic sites in South Carolina. AB - A total of 237 rodents was collected in 4 regions of South Carolina from July 1994 through December 1995. Eight species were collected, including cotton mouse, hispid cotton rat, eastern woodrat, marsh rice rat, white-footed mouse, eastern harvest mouse, golden mouse, and black rat. Of the 1,514 ticks recovered from these hosts, Ixodes minor Neumann, including larvae, nymphs, and adults, was the most abundant species, representing 54% of the total. Only immature stages of other tick species were found, including larvae and nymphs of Dermacentor variabilis (Say), Amblyomma maculatum Koch, Ixodes affinis Neumann, and Ixodes scapularis Say. All 5 tick species parasitized cotton mice, cotton rats, and woodrats, which were the most important small mammal hosts for ticks at the localities studied. Rice rats were hosts of A. maculatum, D. variabilis, and L. minor. Amblyomma maculatum was more strongly associated with cotton rats than other rodent species. Ixodes scapularis was most strongly associated with cotton mice, and I. minor was more strongly associated with both woodrats and cotton mice than other species of rodents. Ixodes minor parasitized hosts in the Coastal Zone only, where among spirochete-infected hosts, it was present in significantly greater numbers than other ticks. Furthermore, I. minor was the only tick species that showed a statistically significant positive association with spirochetal infection in rodents. More I. affinis parasitized spirochete-infected hosts than I. scapularis, but fewer than I. minor. The findings discussed herein provide evidence that implicates I. minor as the possible primary enzootic vector of the Lyme disease spirochete Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt and Brenner in the Coastal Zone of South Carolina. They also indicate that the high level of B. burgdorferi infection in rodents from this region may be a function of the combined involvement of I. minor, I. affinis, and I. scapularis in the enzootic transmission of the spirochete. PMID- 11780826 TI - Sarcocystis neurona infections in sea otter (Enhydra lutris): evidence for natural infections with sarcocysts and transmission of infection to opossums (Didelphis virginiana). AB - Although Sarcocystis neurona has been identified in an array of terrestrial vertebrates, recent recognition of its capacity to infect marine mammals was unexpected. Here, sarcocysts from 2 naturally infected sea otters (Enhydra lutris) were characterized biologically, ultrastructurally, and genetically. DNA was extracted from frozen muscle of the first of these sea otters and was characterized as S. neurona by polymerase chain reation (PCR) amplification followed by restriction fragment length polymorphism analysis and sequencing. Sarcocysts from sea otter no. 1 were up to 350 microm long, and the villar protrusions on the sarcocyst wall were up to 1.3 microm long and up to 0.25 microm wide. The villar protrusions were tapered towards the villar tip. Ultrastructurally, sarcocysts were similar to S. neurona sarcocysts from the muscles of cats experimentally infected with S. neurona sporocysts. Skeletal muscles from a second sea otter failed to support PCR amplification of markers considered diagnostic for S. neurona but did induce the shedding of sporocysts when fed to a laboratory-raised opossum (Didelphis virginiana). Such sporocysts were subsequently fed to knockout mice for the interferon-gamma gene, resulting in infections with an agent identified as S. neurona on the basis of immunohistochemistry, serum antibodies, and diagnostic sequence detection. Thus, sea otters exposed to S. neurona may support the development of mature sarcocysts that are infectious to competent definitive hosts. PMID- 11780827 TI - A survey for Cyclospora spp. in Kenyan primates, with some notes on its biology. AB - From March 1999 through August 2000, 511 stool samples collected from 11 different primate species in 10 geographically distinct locations in Kenya, East Africa, were screened for the presence of Cyclospora spp. oocysts. Positive samples (43/102, 42%) were identified in vervet monkeys (Cercopithecus aethiops) in 4 of 4 locations; 19/206 (9%) in yellow and olive baboons (Papio cynocephalus, P. anubis, respectively) in 5 of 5 locations; and 19/76 (25%) in black and white colobus monkeys (Colobus angolensis, C. guereza, respectively) from 2 of 3 locations. DNA sequences obtained from 18 S rRNA coding regions from respective subsets of these positive samples were typed as Cyclospora cercopitheci (samples from Cercopithecus aethiops). Cyclospora papionis (samples from Papio cynocephalus and P. anubis), and Cyclospora colobi (samples from Colobus angolensis and C. guereza). Cyclospora oocysts were not detected in samples collected from patas, highland sykes, lowland sykes, blue sykes, DeBrazza, or red tailed monkeys. A coded map showing the geographic location of the collected samples is given. Stool samples from 1 troop of vervet monkeys were collected over a 12-mo period. Positive samples ranged between 21 and 63%. These results suggest that there is no strongly marked seasonality evident in Cyclospora infection in monkeys as has been noted in human infection. This is further confirmed by the recovery of positive samples collected from vervet monkeys, baboons, and colobus monkeys at all times of the year during this survey. This absence of seasonality in infection is especially notable because of the extreme weather patterns typical of Kenya, where marked rainy and dry seasons occur. A second noteworthy observation is that the striking host specificity of the Cyclospora species initially described was confirmed in this survey. Baboons were only infected with C. papionis, vervet monkeys with C. cercopitheci, and colobus monkeys with C. colobi, despite geographic overlaps of both the monkey and parasite species and wide geographic distribution of each parasite and monkey host. PMID- 11780828 TI - Adaptation of a strain of Plasmodium vivax from India to New World monkeys, chimpanzees, and anopheline mosquitoes. AB - A strain of Plasmodium vivax from India was adapted to develop in splenectomized Saimiri boliviensis, Aotus lemurinus griseimembra, A vociferans, A. nancymai, A. azarae boliviensis, hybrid Aotus monkeys, and splenectomized chimpanzees. Infections were induced via the inoculation of sporozoites dissected from the salivary glands of Anopheles stephensi and An. dirus mosquitoes to 12 Aotus and 8 Saimiri monkeys; transmission via the bites of infected An. stephensi was made to 1 Aotus monkey and 1 chimpanzee. The intravenous passage of infected erythrocytes was made to 9 Aotus monkeys and 4 chimpanzees. Gametocytes in 13 Aotus monkeys and 4 chimpanzees were infectious to mosquitoes. Infection rates were markedly higher in mosquitoes fed on chimpanzees. PCR studies on 10 monkeys injected with sporozoites revealed the presence of parasites before their detection by microscopic examination. The India VII strain of P. vivax develops in Aotus and Saimiri monkeys and chimpanzees following the injection of parasitized erythrocytes, or sporozoites, or both. The transmission rate via sporozoites to New World monkeys of approximately 50% may be too low for the testing of sporozoite vaccines or drugs directed against the exoerythrocytic stages. However, the strain is highly infectious to commonly available laboratory maintained anopheline mosquitoes. Mosquito infection is especially high when feedings are made with gametocytes from splenectomized chimpanzees. PMID- 11780829 TI - Life cycle of Genarchopsis goppo (Trematoda: Derogenidae) from Nara, Japan. AB - A cystophorous cercaria obtained from Semisulcospira libertina (Gould) from Tobihino, Nara, Honshu, Japan, was used to experimentally infect a freshwater goby Rhinogobius sp. OR via the copepods Mesocyclops leuckarti (Claus), Thermocyclops hyalinus (Rehberg), and Eucyclops sarrulatus (Fisher). It was shown to grow into Genarchopsis goppo Ozaki, 1925. The parasite was found to occur as a natural infection in the stomach of Rhinogobius sp. OR and Odontobutis obscura (Temminck and Schlegel) from Tobihino. PMID- 11780830 TI - Hoplopleura janzeni n. sp. (Phthiraptera: Anoplura), a new sucking louse from a Central American swimming mouse. AB - Both sexes of a new species of sucking louse Hoplopleura janzeni (Phthiraptera: Hoplopleuridae) are described and illustrated from the Central American ichthyomyine swimming mouse Rheomys raptor (Rodentia: Muridae) collected in Costa Rica. The morphology of the new species is compared with that of Hoplopleura exima Johnson, the only other species of sucking louse known to parasitize an ichthyomyine rodent. Hoplopleura janzeni is unique in having posteriorly directed spurs on the first antennal segment, the fore- and midcoxae, and the hind femora of both sexes. PMID- 11780831 TI - Cryptosporidium canis n. sp. from domestic dogs. AB - Oocysts of Cryptosporidium, from the feces of a naturally infected dog and from an HIV-infected human, were identified as the previously reported canine genotype of Cryptosporidium parvum, hereafter referred to as Cryptosporidium canis n. sp. Also among the oocysts from the dog, a trace amount of C. parvum bovine genotype was detected. Cryptosporidium canis oocysts from both the dog and human were infectious for calves. Oocysts excreted by calf 1 (dog source) were approximately 90% C. canis and 10% C. parvum, whereas those excreted by calf 3 (human source) were 100% C. canis. Oocysts from calf 1 infected calf 2 resulting in excretion by calf 2 of oocysts approximately 90% C. parvum and 10% C. canis. Oocysts of C. canis were not infectious for BALB/c neonatal mice or immunosuppressed C57 juvenile mice, although all control mice became infected with the C. parvum Beltsville isolate. Oocysts of C. canis from calf 1 and the human were structurally indistinguishable from oocysts of the C. parvum Beltsville isolate (bovine). However, C. canis oocysts differed markedly at the molecular level from all known species of Cryptosporidium based on sequence data for the 18S rDNA and the HSP 70 gene. The differences in genetics and host specificity clearly differentiate C. canis as a new species. PMID- 11780832 TI - Morphological and molecular description of Haematoloechus meridionalis n. sp. (Digenea: Plagiorchioidea: Haematoloechidae) from Rana vaillanti brocchi of Guanacaste, Costa Rica. AB - An undescribed species of Haematoloechus inhabits the lungs of Rana vaillanti in northwestern Costa Rica. The new species is most similar morphologically to H. medioplexus, having a very small, but well-developed, ventral sucker and lacking extracecal uterine loops, and apparently was mis-identified previously as H. medioplexus in Rana palmipes from Colombia. It differs from H. medioplexus, notably by (1) the shape of the oral sucker, which is elliptical in H. meridionalis and spherical in H. medioplexus; (2) the posterior extent of the vitelline fields, which terminate at the same level in H. medioplexus, but always at different levels in H. meridionalis; (3) the position of the testes, which are immediately posterior to the seminal receptacle and are close together in the new species and far from the seminal receptacle and separated from each other in H. medioplexus; and (4) the location of the genital pore, which is ventral to the cecal bifurcation in the new species and ventral to the pharynx in H. medioplexus. In addition, the new species is unique among members of Haematoloechus by having flaps of tissue on the interior margins of the ventral sucker. The new species shows almost 5% sequence divergence from H. medioplexus in the variable D1 region of the 28s rDNA, complementing the morphological differences. PMID- 11780833 TI - Syngnathinema californiense n. gen., n. sp. (Nematoda: Dracunculoidea) from the circulatory system of the bay pipefish Syngnathus leptorhynchus in California. AB - A new dracunculoid nematode Syngnathinema californiense, n. gen., n. sp., is described from gravid female parasites found inside the heart of wild-caught Bay pipefish Syngnathus leptorhynchus; histologically it was recorded from different sites of the host circulatory system (sinus venosus, atrium, and renal and hepatic veins). The new genus is characterized by the structure of the cephalic end (large oral aperture with a narrow peribuccal ring surrounded by 10 papillae in 2 circles, large circular amphids), division of the esophagus into muscular and glandular portions, location of the well-developed vulva posterior to the esophagus, monodelphic female reproductive organs, and the sharply pointed tail. Because males remain unknown, the genus is provisionally assigned to the Daniconematidae. PMID- 11780834 TI - Phylogenetic and biogeographical relationships among some holarctic frog lung flukes (Digenea: Haematoloechidae). AB - A phylogenetic study of 8 North American and European species of frog lung flukes belonging to Haematoloechus was conducted using approximately 850 to 1,000 bases of the intemal transcribed spacer region (ITS 1 + 5.8S + ITS 2) and 1,250 bases of the large subunit (LSU) of the nuclear ribosomal DNA. Adequate phylogenetic resolution could not be obtained from 5.8S or ITS 2 data. Analysis of ITS 1 data produced 2 equally parsimonious trees that differed only in the position of Haematoloechus breviplexus relative to H. medioplexus and H. varioplexus. Single, identical trees were produced by analysis of both LSU sequence data and a data set comprised of all ITS and LSU data. All trees demonstrated 3 distinct evolutionary lineages within the Holarctic Haematoloechus examined. The results confirmed the taxonomic validity of H. abbreviatus and demonstrated that the presence or absence of extracecal uterine loops is not a character meaningful to the recognition of evolutionary lineages or differentiation of genera. Examination of ITS sequence data revealed almost no intraspecific variation within 5 species of Haematoloechus and demonstrated an approximately 150-base indel common to the North American H. longiplexus and the European H. asper. Two of 3 clades revealed by the phylogenetic analyses are comprised of both European and North American species, indicating that lineages of Haematoloechus arose before the breakup of Laurasia and radiated after Eurasia and North America split. Within each of 3 evolutionary lineages, members share similar patterns of arthropod host specificity distinct from patterns found in the other lineages. This suggests that second intermediate host specificity may be a trait that has been conserved through evolutionary time. PMID- 11780835 TI - Nitrophenide (Megasul) blocks Eimeria tenella development by inhibiting the mannitol cycle enzyme mannitol-1-phosphate dehydrogenase. AB - Unsporulated oocysts of the protozoan parasite Eimeria tenella contain high levels of mannitol, which is thought to be the principal energy source for the process of sporulation. Biosynthesis and utilization of this sugar alcohol occurs via a metabolic pathway known as the mannitol cycle. Here, results are presented that suggest that 3-nitrophenyl disulfide (nitrophenide, Megasul), an anticoccidial drug commercially used in the 1950s, inhibits mannitol-1-phosphate dehydrogenase (M1PDH), which catalyzes the committed enzymatic step in the mannitol cycle. Treatment of E. tenella-infected chickens with nitrophenide resulted in a 90% reduction in oocyst shedding. The remaining oocysts displayed significant morphological abnormalities and were largely incapable of further development. Nitrophenide treatment did not affect parasite asexual reproduction, suggesting specificity for the sexual stage of the life cycle. Isolated oocysts from chickens treated with nitrophenide exhibited a dose-dependent reduction in mannitol, suggesting in vivo inhibition of parasite mannitol biosynthesis. Nitrophenide-mediated inhibition of MIPDH was observed in vitro using purified native enzyme. Moreover, MIPDH activity immunoprecipitated from E. tenella infected cecal tissues was significantly lower in nitrophenide-treated compared with untreated chickens. Western blot analysis and immunohistochemistry showed that parasites from nitrophenide-treated and untreated chickens contained similar enzyme levels. These data suggest that nitrophenide blocks parasite development at the sexual stages by targeting M1PDH. Thus, targeting of the mannitol cycle with drugs could provide an avenue for controlling the spread of E. tenella in commercial production facilities by preventing oocyst shedding. PMID- 11780836 TI - Isolates of Sarcocystis falcatula-like organisms from South American opossums Didelphis marsupialis and Didelphis albiventris from Sao Paulo, Brazil. AB - Isolates of Sarcocystis falcatula-like organisms from South American opossums were characterized based on biological and morphological criteria. Sporocysts from intestinal scrapings of 1 Didelphis marsupialis and 8 Didelphis albiventris from Sao Paulo, Brazil, were fed to captive budgerigars (Melopsittacus undulatus). Budgerigars fed sporocysts from all 9 isolates became ill and S. falcatula-like schizonts were identified in sections of their lungs by immunohistochemical staining. Sarcocystis falcatula-like organisms were cultured from lungs of budgerigars fed sporocysts from D. marsupialis and from lungs of budgerigars fed sporocysts from 3 of 8 D. albiventris. The 33/54 locus amplified by polymerase chain reaction from culture-derived merozoites contained both a HinfI endonuclease recognition site previously suggested to diagnose S. falcatula and a DraI site thought to diagnosed S. neurona. Development of the isolate from D. marsupialis was studied in cell culture; its schizonts divided by endopolygeny, leaving a residual body. Morphological and genetic variation differentiated this Sarcocystis isolate originating in D. marsupialis from the Cornell I isolate of S. falcatula. This is the first report of a S. falcatula infection in the South American opossum, D. marsupialis. PMID- 11780837 TI - Characterization and large-scale expression of the recombinant cysteine proteinase from adult Clonorchis sinensis. AB - Cysteine proteinases play important roles in the pathogenesis of several parasitic infections and have been proposed as targets for the structure-based approach of drug design. As the first step toward applying this strategy to design inhibitors as antiparasitic agents for Clonorchis sinensis, we overexpressed and characterized the 24-kDa cysteine proteinase from adult worms. First, the partial cysteine proteinase gene from C. sinensis was cloned by performing reverse transcription polymerase chain reaction (RT-PCR) with degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences. The 5' and the 3' regions of the cysteine proteinase gene were amplified using the PCR protocol for the rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR). The cDNA has an open reading frame of 981 bp, and the deduced amino acid sequence shares similarity with the cathepsin L like cysteine proteinases from Schistosoma mansoni, Paragonimus westermani metacercaria, Fasciola hepatica, and human cathepsin L by 52%, 47%, 34%, and 29%, respectively. The cysteine proteinase was then overexpressed in the yeast Pichia pastoris as an active enzyme on a large-scale basis (19.7 mg/L). The active recombinant enzyme was purified from culture media using a Ni2+-NTA-agarose affinity column and gel filtration chromatography. This 24-kDa recombinant protein exhibited a substrate preference for Z-Phe-Arg-AMC (benzyloxycarbonyl-L phenylalanyl-L-arginine-7-amino-4-methyl-coumarin) compared with Z-Arg-Arg-AMC, and the activity was inhibited by E-64 (L-trans-epoxysuccinylleucylamido(4 quanidino)butane). PMID- 11780838 TI - Occurrence of cattle Sarcocystis species in raw kibbe from Arabian food establishments in the city of Sao Paulo, Brazil, and experimental transmission to humans. AB - Fifty samples of raw kibbe from 25 Arabian restaurants in the city of Sao Paulo, Brazil, were examined for the presence of bovine Sarcocystis species, using light and electron microscopy, and for infectivity to humans. Sarcocysts were found in all 50 samples. Based on cyst wall structure, S. hominis (94%), S. hirsuta (70%), and S. cruzi (92%) were identified (mostly as mixed infections). Different raw kibbe samples, positive for S. hominis in fresh preparations, were offered as a meal for 7 human volunteers. Six volunteers (85.7%), 2 of whom developed diarrhea, excreted sporocysts in feces. The prepatent period lasted 10-14 (12 +/- 1.8) days and the patent period lasted 5-12 (8.8 +/- 1.1) days. PMID- 11780839 TI - Titration of subcutaneously administered eprinomectin against mature and immature nematodes in cattle. AB - Eprinomectin has been approved for use as a topically applied endectocide for beef and dairy cattle. To determine if eprinomectin has utility as an injectable anthelmintic, it was titrated at 0.05, 0.1, and 0.2 mg/kg s.c. against adult (Trial 1) and at 0.05, 0.1, 0.14, and 0.2 mg/kg s.c. against immature (Trial 2) stages of lung and gastrointestinal nematodes in cattle. In Trial 1, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Adult C. oncophora was the only exception. However, even against this species, the lowest dose of 0.05 mg/kg showed 93% efficacy, and the efficacious dose necessary to kill 95% (ED95) of adults was 0.056 mg/kg. In Trial 2, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against the immature stages of all of the above species of endoparasites. As a result, ED95 values could not be calculated. Consequently, the exquisite potency against endoparasites through parenteral administration suggests that eprinomectin may also have potential utility as an injectable product for cattle. PMID- 11780840 TI - Intestinal distribution of worms and host ingesta in Nippostrongylus brasiliensis. AB - The gastrointestinal nematode Nippostrongylus brasiliensis is thought to feed on host ingesta, and it is generally thought that the presence of ingesta determines the distribution of this parasite within the host intestine. However, these assertions have not been supported by direct evidence. The purpose of this study was to test the hypothesis that N. brasiliensis worms are preferentially found in regions of the host small intestine containing ingesta. The relationship between worm and ingesta distribution was investigated using mice infected with N. brasiliensis and killed on day 8 postinfection at 0130, 0730, 1330, or 1930 hr. There was an inverse relationship between worm and ingesta distributions, and the worms were distributed significantly more anteriad in the intestine than host ingesta, at all times during the 24 hr. To determine what the worms fed on, host ingesta, tissue, and blood were differentially labeled with the fluorescent dyes rhodamine B and Fluoresbrite. The results of this study suggest that N. brasiliensis feeds on the host's intestinal wall, and that habitat distribution of this parasite within the small intestine is not directly related to the presence of luminal ingesta. PMID- 11780841 TI - High-resolution typing of Toxoplasma gondii using microsatellite loci. AB - High-resolution typing of Toxoplasma gondii is essential to understand the effect of genetic differences among strains on the variation in disease manifestation and transmission patterns. Current typing methods discern 3 lineages with minimal within-lineage variation. Described here are 6 new variable loci. These loci, including a minisatellite and 5 microsatellites, were more polymorphic than allozymes, restriction fragment length polymorphisms, and sequence variation in introns. Most importantly, these loci revealed, for the first time, substantial within-lineage variation that was over 6-fold higher than that detected by other markers. Genotyping at these loci facilitates classification of isolates beyond the lineage level. PMID- 11780842 TI - Parasitemia and early tissue localization of Sarcocystis neurona in interferon gamma gene knockout mice fed sporocysts. AB - Early localization and parasitemia of Sarcocystis neurona were studied in gamma interferon gene knockout (KO) mice fed S. neurona sporocysts. Mice were examined for S. neurona infection histologically and immunohistochemically and by bioassay in KO mice. For bioassay, blood and tissue homogenates were inoculated subcutaneously into KO mice. Parasitemia was demonstrated by bioassay in KO mice 1-8 days after feeding sporocysts (DAFS). Sporozoites were seen in histologic sections of all regions of the small intestine and in cells in Peyer's patches of a mouse killed 6 hr after feeding sporocysts. At 1 DAFS, organisms were present in all regions of the small intestine and were also seen in mesenteric lymph nodes. At 3 DAFS, organisms had begun to invade extraintestinal tissues. Sarcocystis neurona was demonstrated histologically in mouse brain as early as 4 DAFS. PMID- 11780843 TI - Interaction between Gammarinema gammari (Nematoda), Microphallus papillorobustus (Trematoda) and their common host Gammarus insensibilis (Amphipoda). AB - The influence of the nematode Gammarinema gammari on survival, mating success, and fecundity of its host Gammarus insensibilis (Amphipoda) was investigated. The prevalence and the mean intensity of G. gammari were significantly higher in males than in females. There was a positive and significant relationship between the mean number of G. gammari and male body size, suggesting that accumulation of this parasite had no significant effect on the survival of its host. Males that harbored the metacercariae of the trematode Microphallus papillorobustus had a lower number of nematodes than those that did not harbor the trematode. Fecundity was significantly reduced in infected females, and unpaired females tended to be more frequently infected by G. gammari than paired ones. However, we found no evidence for parasite-mediated reduction in male competitiveness because the mean number of G. gammari was not significantly different between paired and unpaired males. PMID- 11780844 TI - Molecular detection of Ehrlichia phagocytophila genogroup organisms in larvae of Neotrombicula autumnalis (Acari: Trombiculidae) captured in Spain. AB - Twenty unfed larvae of Neotrombicula autumnalis (Acari: Trombiculidae) collected on vegetation in the north of Spain were examined by polymerase chain reaction for Borrelia burgdorferi (s.l.). rickettsiae, and the Ehrlichia phagocytophila genogroup. At least 10% of the larvae were found to contain granulocytic ehrlichiae. Because the larvae were unfed, they would necessarily have inherited the bacteria through a transovarian transmission pathway. PMID- 11780845 TI - Analysis of a growth-promoting factor for Babesia caballi cultivation. AB - Serum-free media were examined to culture Babesia caballi. Daigo's T (DT) basal medium supplemented with Daigo's GF21 (GF21) or GIT medium, which already contains GF21, supported the parasite propagation at 37 C in a humidified atmosphere under 5% CO2 in air. Growth of B. caballi was dependent of the suitable concentration (10-20%) of GF21. Therefore, GF21 was suggested as the growth-promoting factor for B. caballi. However, GIT medium did not support the growth of parasites from cryopreserved stabilates, and serum supplementation was essential for the retrieval of parasites. PMID- 11780846 TI - Isolation of Neospora caninum from the brain of a pregnant sheep. AB - Neospora caninum was isolated from the brain of a naturally infected pregnant sheep by inoculation of immunodeficient mice with a homogenate of the brain tissue. The ewe showed no clinical signs. Tachyzoites were observed in the tissues of the nu/nu mice injected with the brain tissue homogenate and the diagnosis was confirmed by immunohistochemical staining with anti-N. caninum antibodies and by detecting N. caninum-specific DNA by polymerase chain reaction. PMID- 11780847 TI - Non-isotopic detection of Tetramicra brevifilum (Microspora) DNA in turbot tissues. AB - A non-isotopic in situ hybridization (ISH) method was developed for detection of Tetramicra brevifilum, a commercially important parasite in farmed turbot Scophthalmus maximus. The probe relies on sequences from the small-subunit rRNA gene (SSUrDNA) of Tetramicra brevifilum and was obtained by polymerase chain reaction then labeled with digoxigenin. The results obtained demonstrate that the probe hybridizes well with genomic DNA of the spores; thus, it is an effective method for detecting multiorgan infections of turbot by T. brevifilum. PMID- 11780848 TI - Importance of gender and sex hormones in regulation of susceptibility of the small intestine to peroral infection with Toxoplasma gondii tissue cysts. AB - This study was performed to investigate whether the gender and sex hormones play a role in susceptibility of the small intestine of mice to peroral infection with Toxoplasma gondii tissue cysts. Female animals died significantly earlier than males, and early mortality of females was associated with greater numbers of tachyzoites and severe necrosis in their small intestines. Treatment of female mice with testosterone resulted in markedly reduced intestinal parasite numbers and pathology. Thus, the gender and sex hormones are important factors for determining susceptibility of the small intestine to T. gondii infection. PMID- 11780849 TI - Serological diagnosis of neosporosis in a herd of dairy cattle in southern Brazil. AB - Neospora caninum-specific antibodies were detected in 60 of 172 (34.8%) dairy cattle by enzyme-linked immunosorbent assay (ELISA) in a herd from Parana State, Brazil. The seropositive animals included 47 of 126 (37.3%) adult cows, 7 of 29 (24%) heifers (1-2 yr), 4 of 15 (27%) heifers (5 mo-1 yr), and 2 precolostral samples. Data collected over a 9-yr follow-up period revealed that the proportion of pregnancies ending in abortion was 20% (31/154) among ELISA seropositive cows and 8% (15/193) among seronegative cows. The farm recorded 46 abortions, of which 31 (67.3%) were from seropositive cows. All sera positive by ELISA (n = 60) and sera from cows (n = 11) that were ELISA-negative but that had aborted were tested by the indirect fluorescent antibody test (IFAT) at dilutions from 1:25 to 1:200. All sera from ELISA-positive cows (n = 47) had an IFAT titer of 1:25:35 (74%) of these sera were also seropositive at a dilution of 1:200 (IFAT). Cows seropositive by ELISA had a 4-fold increased risk of having aborted at least once, compared to ELISA-seronegative cows. This association was statistically significant (P = 0.0016). The attributable fraction for this association indicated that approximately 76% of the risk for a cow having a history of abortion was attributable to seroconversion to N. caninum. PMID- 11780850 TI - Seasonal fluctuations of incubation, healing delays, and clinical presentation of cutaneous leishmaniasis in French Guiana. AB - An investigation was conducted to determine whether seasonal variations affected the development of cutaneous leishmaniasis. Data from 499 cases treated between July 1994 and December 1998 were analyzed. The interval between infection and consultation and between treatment and clinical cure varied significantly between cases with an incubation period during the dry season compared with the rainy season (P < 0.001). When the incubation period occurred during the dry season, the standard pentamidine isethionate treatment seemed to be less effective (i.e.. the odds ratio for failure was 1.9 [1.1-3.4], P = 0.01). The presence of lymphangitis was more frequent during the dry season (i.e., the odds ratio was 0.26 [0.15-0.45], P < 0.001). These results suggested that the observed seasonal variations were due to variations in the host/parasite balance. Converging indirect elements that suggest a role for variations in solar ultraviolet radiation are discussed. PMID- 11780851 TI - Hunting practices increase the prevalence of Trichinella infection in wolves from European Russia. AB - From 1998 to 2000, 184 animals (82 wolves, 29 red foxes, 55 mustelids, 5 raccoon dogs, and 13 domestic dogs), mainly shot by hunters in the Tvier and Smoliensk regions of northwest European Russia, were tested for Trichinella larvae; 98 animals (53.3%) were found to be positive. The highest prevalence was detected in wolf (97.5%). Trichinella nativa was the most common species detected (98%). The diet of wolves was investigated by examining the stomach contents of 62 animals (75.6% of the total number of wolves examined for Trichinella). It consisted mainly of dog (36.4% of the total number of occurrences of all food items, PFO) and moose (31.2 PFO); however, during the hunting seasons of 1998-1999 and 1999 2000, skinned wolf carcasses were left in the forest as bait (567 carcasses, about 18,000 kg). This very high prevalence of Trichinella infection, the highest ever detected in a natural population of carnivores, could be explained by carnivore-carnivore transmission, influenced by the hunting practices adopted in the study area. PMID- 11780852 TI - Improving the rate of infectivity of Cryptosporidium parvum oocysts in cell culture using centrifugation. AB - Centrifugation was evaluated as a method to improve infectivity assays of Cryptosporidium parvum in cell culture using the focus detection method, an immunofluorescence-based method for detecting infectious C. parvum oocysts in vitro. Human ileocecal adenocarcinoma (HCT-8) cells were grown for 48 hr on 13-mm cover slips in 24-well microtiter plates and infected with bleach-treated C. parvum oocysts. Plates were centrifuged at 228 g for 10 min and incubated at 37 C for 5, 12, 18, 24, and 48 hr. Foci of infection were stained by immunofluorescence and enumerated using epifluorescent microscopy. Results were compared to noncentrifuged controls. Foci in centrifuged samples could be enumerated after 18 hr. According to most probable number (MPN) analysis, the number of infectious oocysts estimated at 48 hr (13,326 infectious oocysts) was reached by 18 hr in centrifuged samples. After 48 hr, there was no significant difference (P < 0.05) between centrifuged and noncentrifuged samples enumerated by number of foci or the MPN of infectious oocysts. Centrifugation may expedite detection during C. parvum infectivity assays. Furthermore, multiwell plate formats are more cost effective than traditional chamber slides. PMID- 11780853 TI - Politics and humanitarian aid. PMID- 11780854 TI - New humanitarianism: does it provide a moral banner for the 21st century? AB - There is a 'new humanitarianism' for the new millennium. It is 'principled', 'human-rights based' and politically sensitive. Above all it is new. It marks a break from the past and a rejection of the traditional principles that guided humanitarianism through the last century. New humanitarians reject the political naivety of the past, assess the long-term political impact of relief and are prepared to see humanitarian aid used as a tool to achieve human rights and political goals. New Humanitarianism is compelling, in tune with our times and offers a new moral banner for humanitarians to cling to as we enter the new millennium. Or does it? After outlining the key elements of new humanitarianism, including the human rights approach and developmental relief, the paper spells out some of the dangers. The author claims that new humanitarianism results in an overt politicisation of aid in which agencies themselves use relief as a tool to achieve wider political goals. The paper shows how this approach has spawned a new conditionality which allowsfor aid to be withheld and has produced a moral hierarchy of victims in which some are more deserving than others. The paper concludes with a plea for a revival of the principle of universalism as the first step to a new set of principles. PMID- 11780855 TI - Apples, pears and porridge: the origins and impact of the search for 'coherence' between humanitarian and political responses to chronic political emergencies. AB - During the 1990s a consensus emerged within the international humanitarian system that there was a need to enhance the 'coherence' between humanitarian and political responses to complex political emergencies. Closer integration between aid and political responses was seen to be necessary in order to address the root causes of conflict-induced crises, and to ensure that aid did not exacerbate political tensions. This paper explores the theory and practice of coherence over the past decade. It argues that, by sleight of hand, the coherence agenda has been reinterpreted such that humanitarian action has become the primary form of political action, rather than merely a substitute for it. The coherence agenda has been driven by geopolitical events, domestic policy considerations in donor countries and the more parochial concerns of aid policy, and is reflected in a number of substantive changes in the humanitarian architecture. Many of the tenets of this 'new humanitarianism' have been embraced by the majority of relief agencies, and thus legitimised it. The paper concludes that political humanitarianism, as opposed to active engagement by political and military actors, is flawed ethically and technically. It will provide neither an effective palliative for the ill effects of war, nor address its causes. PMID- 11780856 TI - Governing the borderlands: decoding the power of aid. AB - This article examines aid practice, that is, the public-private contractual networks that link donor governments, UN agencies, military establishments, NGOs, private companies and others, as a relation of global liberal governance. In order to fulfil this function, such networks embody what could be called the 'securitisation' of international assistance. Based upon ideas of human security and ameliorating the effects of poverty and vulnerability reduction, aid is now seen as playing a direct security role. Rather than being concerned with relations between states, the primary aim of this security paradigm is to modulate and change the behaviour of populations within them. In doing so, it is able to exploit the opportunities afforded by privatisation. At the same time, however, aid as security is confronted by its own particular problem of 'governing at a distance'; how can calculations made by leading states be transformed into actions at the global edge when a multitude of private and non government implementors now intervene? The article concludes by examining the contribution of risk analysis to solving this problem and, especially, the development of new contractual regimes based around technical standardisation, benchmarking and performance auditing. Through such technologies, metropolitan states are learning how to manage the public-private networks of aid practice and, as a result, to govern the borderlands in new ways. PMID- 11780857 TI - Politicisation of humanitarian aid and its consequences for Afghans. AB - This paper outlines the implications of international approaches to humanitarian assistance in Afghanistan, focusing in particular on the period since the Taliban assumed power. It argues that international efforts to use conditionality on humanitarian assistance have proved ineffective in influencing the Taliban's policies, and have been implemented despite the negative impact on the welfare of the whole population. Efforts to adopt a principled approach to aid programming in this environment have also raised many ethical dilemmas which are likely to remain major challenges in that country and elsewhere. PMID- 11780858 TI - Humanitarian war: a new consensus? AB - The NATO bombing operation Allied Force against Yugoslavia in March-June 1999 represents the final disappearance of the narrowing divide between humanitarianism and politics: a war initiated and justified on humanitarian grounds. Although unlikely to be repeated any time soon, the Kosovo case appears to have cemented an ideological shift on the international right and even necessity of sing military force to protect civilians within sovereign states. Rather than humanitarians acknowledging the political context and consequences of their work, however, the case suggests the embrace of humanitarian principles of universality and neutrality by military organisations. This article discusses some consequences of the new consensus: neglect of the political context (both local and foreign) of such operations, interaction between the operational dynamics of relief operations and the logic of war and the political consequences of using the humanitarian legitimation and mission in such cases. PMID- 11780859 TI - The challenge of civil-military relations in international peace operations. AB - The relationship between military and civilian humanitarian organisations has developed in an increasingly integrative way. Military initiatives to institutionalise the relationship, since the interventions in Somalia and the Balkans, entail a dilution of humanitarian independence as was manifested in practice in Kosovo. Further, the state-centric foundations of military intervention run counter to the potential for humanitarian organisations to foster a cosmopolitan ethos that would not only preserve humanitarian principles but also contest statist assumptions about conflict, development and power. PMID- 11780860 TI - Therapeutic governance: psycho-social intervention and trauma risk management,. AB - This paper critically analyses the significance of psycho-social intervention as a new form of international therapeutic governance based on social risk management. First, the paper examines the international psycho-social model and its origins in an Anglo-American therapeutic ethos. Second, the paper argues that psycho-social approaches jeopardise local coping strategies. Third, the paper highlights the potential political, social and psychological consequences of the pathologisation of war-affected societies. Finally the paper concludes that therapeutic governance represents the reduction of politics to administration. PMID- 11780861 TI - Complement activation in the human brain after traumatic head injury. AB - The complement cascade has been suggested to be involved in the development of secondary brain injuries following brain contusions, based on animal experiments. The aim of the present study was to examine the possible involvement of the complement cascade following traumatic head injury in the human brain. Sixteen patients were included in this study, 12-77 years of age, treated at the neurointensive care unit for traumatic brain contusions. All of these patients were operated with frontal or temporal lobe resection due to intractable intracranial hypertension. The resected tissue was analyzed with regard to components related to complement activation. The time interval between accident and operation was 2-82 h. Brain tissue from three patients operated with hippocampectomy due to epilepsy, including temporal lobe resection, were used as controls. We found increased immunoreactivity for complement components C1q, C3b, and C3d and the membrane attack complex (MAC), C5b-9, in the immediate vicinity of neurons in the penumbra area of the contusion. These findings constitute histological evidence for activation of the complement cascade in the penumbra of cortical contusions in the human brain. Using in situ hybridization, we also found C3-mRNA in the penumbra, suggesting a local synthesis of complement. Furthermore, upregulation of the endogenous complement regulator clusterin was found in some neurons in the same area. We suggest that unknown compounds in the debris from injured neurons or myelin breakdown products trigger complement activation, including formation of C5b-9. Activated complement components may stimulate accumulation of inflammatory cells and formation of brain edema, as well as having membrane destructive effects by the end product MAC, thereby being mediators in the development of secondary brain damage. PMID- 11780862 TI - Repinotan (BAY x 3702): a 5HT1A agonist in traumatically brain injured patients. AB - Repinotan is a high-affinity, selective, full agonist of the 5HT1A-receptor subtype with neuroprotective properties. This paper presents the results of a randomized, double-blind, placebo-controlled study examining the safety and tolerability of three different doses of repinotan in patients with severe traumatic brain injury. Sixty patients were enrolled to receive repinotan (0.5, 1.25, or 2.50 mg/day) or placebo, by continuous i.v. infusion for 7 days. Repinotan treatment had no apparent adverse effects on intracranial pressure, hemodynamic parameters or laboratory parameters. No seizures occurred during treatment, and the incidence and severity of adverse events was as expected for this indication. No serious adverse events were considered related to drug treatment, with the possible exception of one case of inappropriate ADH secretion. No further safety concerns were raised during the 3 months following treatment. On a descriptive basis, the proportion of patients having good outcome or moderate disability (Glasgow Outcome Scale) was somewhat greater in repinotan treated patients (60%) than in placebo (50%). PMID- 11780863 TI - Focal cerebral hyperemia in postconcussive amnesia. AB - Transient amnesia caused by minor head injury is commonly encountered in daily neurosurgical practice, but the mechanism of such amnesia has not been extensively studied. We measured the regional cerebral blood flow (rCBF) of patients with postconcussive amnesia with Xe/CT CBF to examine whether a focal disturbance of CBF exists. The Xe/CT CBF study was performed in eight patients with closed head injury without organic cerebral lesion while they were suffering from posttraumatic amnesia (concussion group). The time interval between accident and CBF measurement was less than 2 h in three patients, 5-6 h in two, 8-9 h in two, and 18 in one. The results were compared with those of nine normal volunteers and eight other age-matched patients who recovered without any neurological deficit despite the presence of hemorrhagic regions (mild hemorrhage group). The rCBF of the concussion group was significantly elevated in the bilateral mesial temporal cortex in comparison to the normal group. The rCBF in the mild hemorrhage group was lower than that of normal controls in all regions. The analysis of right-left difference in CBF indicated that there was significant asymmetry (right > left) in the frontal and temporal cortex in the concussion group, but not in the normal and mild hemorrhage group. This Xe/CT CBF study in acute stages of cerebral concussion, in which patients were amnestic, detected focal cerebral hyperemia. Such hyperemia in regions closely related to human memory function may be the result of vasoparalysis or the compensatory activation of memory circuits after denervation injury. PMID- 11780864 TI - Neuronal apoptosis inhibitory protein expression after traumatic brain injury in the mouse. AB - Apoptosis of brain cells is triggered by traumatic brain injury (TBI) and is blocked by caspase inhibitors. The neuronal apoptosis inhibitor protein (NAIP), which has been shown to inhibit apoptosis by both caspase-dependant and caspase independent mechanisms, is neuroprotective in rat models of cerebral ischemia and axotomy. In order to gain a better appreciation of CNS apoptosis following head injury in general and the possible involvement of NAIP specifically, we have configured a mouse model of TBI. In addition to demonstrating apoptosis, the spatiotemporal expression or levels of a number of proteins with apoptosis modulating effects have been determined. Apoptosis of neurons and oligodendrocytes following TBI was observed in brain sections which were triple stained with in situ end labeling, bisbenzimide and immunofluorescent stain for neuron specific nuclear protein and myelin-associated glycoprotein, respectively. Further evidence for apoptosis following TBI in this model was obtained in brain samples using ligation-mediated PCR amplification of DNA fragments and gel electrophoresis. The temporal profile of apoptosis was similar to the temporal profile of microglial activation determined by CD11b staining and TNFa expression induced by TBI. NAIP staining in sections of cerebral cortex and subcortical white matter increased at 6 h and decreased towards control levels at 24 h post TBI. Temporal changes in the expression of NAIP were also observed using Western blot analysis of brain samples removed from injured cortex and sub-cortical white matter. At the time that NAIP expression decreased markedly (24 h post-TBI), procaspase-3 levels also decreased, PARP cleavage increased, and the highest levels of apoptosis were observed. These findings have implications in our understanding of traumatically induced programmed cell death and may be useful in the configuration of therapies for this common injury state. PMID- 11780865 TI - Elevation of extracellular glutamate in the final, ischemic stage of progressive epidural mass lesion in cats. AB - Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to investigate the impact of intracranial pressure on accumulation of neuroactive substances, we gradually raised intracranial pressure in five halothane anesthetized cats by inflation of an epidural balloon. We evaluated in the parietal cortex contralateral to the site of balloon inflation, alterations of extracellular glutamate and purine catabolites and of the lactate/pyruvate ratio in relation to changes of intracranial, cerebral perfusion and mean arterial blood pressure. In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography. In this simplified mass lesion model, extracellular glutamate increased in all cats at a late, critical stage after tentorial herniation, when intracranial pressure had increased to more than 90 mm Hg, cerebral perfusion pressure had decreased below 40-50 mm Hg. Positron emission tomography assessments revealed that the ischemic threshold for glutamate accumulation was in the range of 15-20 mL/100 g/min. Purine catabolites and the lactate/pyruvate ratio increased somewhat earlier than glutamate, but also after reaching the critical, terminal stage. We conclude that in this model of progressive epidural compression, glutamate mediated excitotoxic processes at sites remote from the initial focal lesion depend on processes such as delayed ischemia in combination with tentorial herniation and systemic hypotension. These processes seem to be initiated by a decrease of cerebral perfusion pressure below a threshold of 40-50 mm Hg. PMID- 11780866 TI - Contrasting effects of dopamine therapy in experimental brain injury. AB - Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. This study therefore examined the effects of dopamine on physiological and MRI/MRS parameters in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion. Dopamine was capable of restoring CPP in the model of rapidly rising ICP. This CPP restoration was associated with a partial restoration of CBF. Two profiles of change in the Apparent Diffusion Coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Dopamine did not alter these profiles. MRI assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury; significantly in the group with a persistently low ADCw (p < 0.01). In contusional injury, dopamine significantly worsened edema in both the ipsi- and contralateral hippocampus and temporal cortex. This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated. PMID- 11780867 TI - The hypothalamo-pituitary-adrenal axis response to experimental traumatic brain injury. AB - Alterations in the hypothalamo-pituitary-adrenal (HPA) axis following traumatic brain injury have not been documented in detail. We used fluid percussion injury (FPI) to evaluate the early changes in components of the HPA axis following experimental traumatic brain injury. Wistar rats were sacrificed at 2 or 4 h following sham or FPI surgery. In situ hybridization histochemistry was used to determine the expression of mRNAs of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus and pro-opiomelanocortin (POMC) in the pituitary. A group of animals undergoing no surgery were used as control. Repeated blood sampling from an indwelling catheter demonstrated that plasma corticosterone (CORT) levels peaked 30 min following surgery in sham and FPI animals but there was no significant difference in CORT concentration between these groups at any time. Pituitary POMC expression was increased following sham and FPI surgery (compared with control non-operated animals) but with no significant difference between the two groups undergoing surgery. Hypothalamic CRH mRNA expression was significantly higher in animals undergoing FPI compared with sham surgery. Hypothalamic AVP mRNA expression was not significantly increased when compared with control nonoperated animals. These data indicate that the anaesthesia and/or surgery associated with FPI or sham surgery induces a generalised activation of the HPA axis. The selective increase in CRH mRNA in animals undergoing FPI may be due to specific effects of traumatic brain injury rather than a general stress response and may suggest an additional neurotransmitter role for CRH following head injury. The absence of an AVP response suggests that the effects of FPI may be mediated through the CRH-alone containing subpopulation of neurons. PMID- 11780868 TI - Kinematic analyses of air-stepping of neonatal rats after mid-thoracic spinal cord compression. AB - Although human infants suffer traumatic spinal cord injury, appropriate animal models have not been developed. The consequences of neonatal injury are not necessarily the same as in adults, so treatments designed for adults may not generalize to infants. Therefore, understanding the effects of traumatic injury to the developing cord is important. In this experiment, mid-thoracic spinal cords of 4-day-old rats were compressed with forceps by 0% (sham), 90% or 95% of the uncompressed width. On postoperative day (POD) 1 or 11, rats were suspended in harnesses and administered L-DOPA to activate locomotor circuits. Slight modifications of interlimb coordination remained on POD 11 following the lesser compression, whereas the amount of hindlimb air-stepping, step rates, step lengths and coordination were reduced and declined post-operatively following the greater compression. Lesions were proportional to severity of compression. Progressive motor dysfunction during air-stepping revealed deficits in descending control of lumbar circuits, whereas previous reports of recovery of overground walking probably reflect activation of reflex mechanisms caudal to the transection. PMID- 11780869 TI - A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. AB - This paper describes a modification of a balloon-compression technique to produce spinal cord injury in adult rats. A 2-French Fogarty catheter is inserted into the dorsal epidural space through a small hole made in T10 vertebral arch, advanced cranially to T8-9 spinal level, and inflated for 5 min. Spinal cord damage is graded by increasing the volume of saline used to inflate the balloon. Quantitative neurological and histopathological outcomes are presented with three different volumes (10, 15, and 20 microl of saline) to characterize the gradation of injury. Volume of 15 microl produced complete paraplegia followed by gradual recovery, finally reaching approximately the middle of the scale used to quantitate the locomotor performance. With these animals, after 4 weeks, the center of the lesion shows complete loss of grey matter and partial sparing of the white matter. We conclude that 15 microl volume produced submaximal injury that will be useful for studying the pathophysiology and effects of protective therapies with this compression-injury model. PMID- 11780870 TI - Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 2: illustrating their mechanism of action. PMID- 11780871 TI - Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases. AB - BACKGROUND: The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. METHOD: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement. Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. RESULTS: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature. and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. CONCLUSION: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders. PMID- 11780872 TI - Do vitamins or minerals (apart from lithium) have mood-stabilizing effects? PMID- 11780873 TI - Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. AB - BACKGROUND: To determine in open trials the therapeutic benefit of a nutritional supplement for bipolar disorder. METHOD: The sample consisted of 11 patients with DSM-IV-diagnosed bipolar disorder aged 19 to 46 years, who were taking a mean of 2.7 psychotropic medications each at study entry. Three additional patients dropped out prematurely. The intervention is a broad-based nutritional supplement of dietary nutrients, primarily chelated trace minerals and vitamins, administered in high doses. At study entry and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). RESULTS: For those who completed the minimum 6-month open trial, symptom reduction ranged from 55% to 66% on the outcome measures; need for psychotropic medications decreased by more than 50%. Paired t tests revealed treatment benefit on all measures for patients completing the trial: HAM-D mean score at entry = 19.0, mean score at last visit = 5.4, t = 5.59, df = 9, p < 01; BPRS mean score at entry = 35.3, mean score at last visit = 7.4, t = 2.57, df = 9, p <.05; YMRS mean score at entry = 15.1, mean score at last visit = 6.0, t = 4.11, df = 9, p < .01. The effect size for the intervention was large (> .80) for each measure. The number of psychotropic medications decreased significantly to a mean +/- SD of 1.0+/-1.1 (t = 3.54, df = 10, p < .01). In some cases, the supplement replaced psychotropic medications and the patients remained well. The only reported side effect (i.e., nausea) was infrequent, minor, and transitory. CONCLUSION: Some cases of bipolar illness may be ameliorated by nutritional supplementation. A randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway, as well as open trials in children. PMID- 11780874 TI - Indicators of suicide over 10 years in a specialist mood disorders unit sample. AB - BACKGROUND: There are few firm data to guide the clinician in identifying individual depressed patients who may be at high risk for completing suicide. In particular, there have been few prospective studies of well-characterized depressed patients to determine indicators of such future events. METHOD: Eight hundred thirteen patients with a major depressive episode (DSM-III, DSM-III-R, or DSM-IV criteria) were assessed in detail in a specialist Mood Disorders Unit (MDU) over a 10-year period. Follow-up at the end of that period (mean = 5.1 years) confirmed that 31 patients (3.8%) had completed suicide. The suicide completers were compared on a broad range of clinical and demographic variables obtained at baseline with (1) the total remaining depressed sample, (2) 31 age- and sex-matched subjects who were confirmed to be alive and had never attempted suicide, and (3) 24 age- and sex-matched living subjects who had made at least 1 suicide attempt. RESULTS: The most consistent finding, across all 3 comparisons, was that the suicide completers were more likely to have been inpatients at the time of the index MDU assessment. Other characteristics of completers were a greater number of prior admissions for depression, being older and in a relationship, and being male and married or female and single. Somewhat paradoxically, suicide completers also evidenced fewer previous suicide attempts and less suicidal ideation compared with living subjects who had attempted suicide at the time of index assessment. CONCLUSION: Overall, we were able to find few predictors of later suicide in this sample. Those who completed suicide demonstrated evidence of more severe illness over a lifetime (for example, having more admissions). but revealed less suicidal ideation at the time of the index MDU assessment. While these features were statistically significant, they are of limited usefulness in predicting suicide in an individual patient. PMID- 11780875 TI - The effect of stimulants on nocturnal motor activity and sleep quality in adults with ADHD: an open-label case-control study. AB - OBJECTIVE: Sleep disturbances are common in adults with attention deficit/hyperactivity disorder (ADHD). In a case-control study, adult ADHD was associated with increased nocturnal motor activity and reduced self-perceived quality of sleep. METHOD: Eight adults with DSM-IV-diagnosed ADHD (combined type, N = 7; inattentive type, N = 1) were treated with stimulants in open-label form at 8:00 a.m., 12:00 noon, and 4:00 p.m. The mean daily dose was 51 mg of methylphenidate (range, 30-90 mg) in 7 subjects and 30 mg of dextroamphetamine in 1 subject. Actimeters were used to assess nocturnal motor activity during 6 consecutive nights both at baseline and after 3 weeks of treatment. The data were compared with those of 8 matched normal controls. RESULTS: ADHD patients slept worse and showed significantly higher nocturnal motor activity at baseline compared with controls. No baseline differences between patients and controls were found in sleep latency, number of awakenings, and total time in bed. Changes from baseline to week 3 within the ADHD patients indicated improvement of sleep quality (p = .05) and reduction of Activity Level (p = .10) and Movement Index (p = .07) scores. When within-group changes were compared between ADHD subjects and controls, treatment with stimulants tended to be associated with a reduction of Activity Level (p < .01) and Movement Index (p = .04) scores and improved sleep quality (p = .02) in ADHD patients. Sleep latency, number of awakenings, and total time in bed were unaffected in within-group and between-group analyses. CONCLUSION: The results should be interpreted cautiously given the open-label design and small sample size. Further study is warranted into the influence of stimulants on sleep in larger samples of ADHD patients by using controlled designs, multiple dose levels, and polysomnographic measures. PMID- 11780876 TI - Demographic and clinical features of 131 adult pathological gamblers. AB - BACKGROUND: This study was constructed to detail the demographic and phenomenological features of pathological gamblers. METHOD: One hundred thirty one subjects with DSM-IV pathological gambling were administered a semistructured interview to elicit demographic data and information on the phenomenology, age at onset, course, associated features, treatment history, and response to treatment of the disorder, followed by the Structured Clinical Interview for DSM-IV. RESULTS: Seventy-eight female (59.5%) and 53 male (40.5%) (mean +/- SD age = 47.7+/-11.0 years) pathological gamblers were studied. The majority of subjects (55.7%) were married. Subjects gambled a mean of 16 hours per week. Slot machines (65%), cards (33%), and blackjack (26%) were the most popular forms of gambling. The mean length of time between first gambling behavior and onset of pathological gambling was 6.3+/-8.9 years. Approximately one half (46%) of the subjects reported that television, radio, and billboard advertisements were a trigger to gamble. Most gamblers had severe financial, social, or legal problems. The majority of the subjects (58%) had at least 1 first-degree relative who also exhibited symptoms of problematic gambling behavior. CONCLUSION: Pathological gambling is a disabling disorder associated with high rates of social and legal difficulties. PMID- 11780877 TI - Suicide attempts in bipolar patients. AB - BACKGROUND: Between 25% to 50% of patients with bipolar disorder make suicide attempts during their lives, but there are some controversies about factors related to suicide attempts in this group of patients. The aim of this study is to investigate the association between suicide attempts and the predictive factors previously described in the literature. METHOD: The sample included all 169 patients with DSM-III-R bipolar I disorder identified in a delimited area (northern Spain). Sociodemographic, clinical, and family history variables measured by Research Diagnostic Criteria-Family History were analyzed. Significant variables were introduced in a logistic regression analysis to control for the effects of other variables. RESULTS: There were 56 patients (33%) who had one or more suicide attempts. Early age at onset, history of hospital admission during depressive episodes, drug abuse, and family history were significantly associated with suicide in the univariate analyses (p < .05). A much higher proportion of patients with onset at or before 25 years of age than patients with onset after 25 years of age attempted suicide (23% vs. 10%). The age at onset was no longer significant after controlling for the other 3 variables included in the logistic regression analysis. CONCLUSION: Suicide attempts are highly prevalent in bipolar patients and are related to drug abuse, family history of affective disorders, and severe depressive episodes. This study suggests that the risk of suicide in patients with an early age at onset could reflect other variables such as drug abuse, a history of hospital admissions for depression, or family history. PMID- 11780878 TI - Neuroleptic-related dyskinesias in children and adolescents. AB - BACKGROUND: Few studies have investigated the comparative risk of neuroleptic related dyskinesias in children and adolescents receiving typical versus newer, atypical antipsychotics. This prospective study was completed to test whether clinical use of atypical antipsychotics is associated with less risk for developing neuroleptic-related dyskinesias than clinical use of typical neuroleptics in an unselected heterogeneous population of seriously emotionally disturbed youths admitted to acute residential treatment. We also tested a novel model of predictive risk for neuroleptic-related dyskinesias in children and adolescents. METHOD: 102 children and adolescents receiving typical neuroleptics, atypical antipsychotics, or the combination were studied. Youths developing neuroleptic-related dyskinesias were compared with youths free of dyskinesias over a 3-month study period on demographic, diagnostic, and treatment variables. Logistic regression was utilized to develop a novel model of predictive risk. RESULTS: Of neuroleptic-treated youths, 5.9% had probable tardive dyskinesia, a rate less than the prevalence of tardive dyskinesia in chronic neuroleptic treated adults. Use of typical neuroleptics was significantly (p = .03) associated with dyskinesia compared with use of atypical antipsychotics. Four variables including IQ, initial Abnormal Involuntary Movement Scale score, type of antipsychotic, and cumulative number of risk factors accounted for 35.8% of the variance when predicting dyskinetic status. CONCLUSION: Use of atypical antipsychotics appears to be associated with less dyskinesia risk than typical neuroleptics in an unselected group of seriously emotionally disturbed children and adolescents. Results support a cumulative risk model of neuroleptic-related dyskinesia in youths. PMID- 11780880 TI - Right versus left prefrontal transcranial magnetic stimulation for obsessive compulsive disorder: a preliminary investigation. AB - BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response. PMID- 11780879 TI - Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania. AB - BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania. PMID- 11780881 TI - Citalopram as adjunctive therapy in bipolar depression. AB - BACKGROUND: The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study. METHOD: The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 antipsychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram. RESULTS: Forty five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low. CONCLUSION: The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder. PMID- 11780882 TI - Citalopram in the maintenance treatment of major depressive disorder. PMID- 11780883 TI - Olanzapine, new-onset diabetes mellitus, and risk for insulin overdose. PMID- 11780884 TI - A pilot double-blind, dose-comparison study of risperidone in drug-naive, first episode schizophrenia. PMID- 11780885 TI - A multidisciplinary team approach to skull base chordomas. AB - OBJECT: A multidisciplinary team devised a protocol for long-term care of patients with skull base chordomas. In this study they describe their approach. METHODS: Forty-two patients presented between 1986 and 1998 and were treated by maximum surgical cytoreduction and photon radiation therapy. Tumor volume doubling time determined on the basis of magnetic resonance imaging, immunostaining, and cell proliferation (Ki67 labeling index [LI]) studies indicated growth rates of individual chordomas. The best outlook was associated with the greatest extent of tumor removal achieved during the first operation. There were no deaths associated with patients who underwent first-time surgery, but there was a 7.1% mortality rate associated with those who underwent subsequent operations. Cerebrospinal fluid leaks, additional cranial nerve palsies, and pharyngeal wound problems were the most difficult management problems encountered after second and subsequent surgeries. The time interval between operations was usually between 2 years and 3 years after the first surgery; very few patients required a second surgery, with a quiescent period in excess of 5 years. Life-table 5- and 10-year survival rates were 77% and 69%, respectively. CONCLUSIONS: The authors believe that this series of skull base chordomas provides new insights into the management of these lesions, particularly with regard to techniques that increase survival times and studies that aid in formulating prognoses. PMID- 11780886 TI - A multidisciplinary team approach to skull base chondrosarcomas. AB - OBJECT: The authors review their experience with treating skull base chondrosarcomas, which are much rarer than skull base chordomas and differ from them in prognosis and treatment. METHODS: Seventeen patients (12 male and five female patients) with histologically verified chondrosarcomas were followed up prospectively over a 12-year period. The mean age at presentation was 35.9 years. Most patients presented with cranial nerve palsies. Seven had undergone surgery prior to referral to the authors' unit. All underwent maximum surgical cytoreduction by the most direct surgical approach; only the two patients harboring the mesenchymal variant underwent radiotherapy. CONCLUSIONS: One patient died of a pulmonary embolus; the patients harboring mesenchymal chondrosarcomas died at 20 and 36 months, respectively, after treatment. Of the remaining patients, 93% were alive 5 years postsurgery and had a projected 10 year survival rate of 84% (mean survival time 9.3 years). These data emphasize the very slow progression of this tumor compared with skull base chordoma. PMID- 11780887 TI - A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. AB - OBJECT: The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time. METHODS: The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively. CONCLUSIONS: Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4-14.6 months), compared with 8.8 months (95% CI 7.4-10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1-3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4-5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable. PMID- 11780888 TI - Long-term outcome after gamma knife surgery for secondary trigeminal neuralgia. AB - OBJECT: This study was directed to evaluate the potential role of gamma knife surgery (GKS) in the treatment of secondary trigeminal neuralgia (TN). The authors have identified three anatomicoclinical types of secondary TN requiring different radiosurgical approaches. METHODS: Pain control was retrospectively analyzed in a population of patients harboring tumors of the middle or posterior fossa that involved the trigeminal nerve pathway. This series included 53 patients (39 women and 14 men) treated using GKS between July 1992 and June 1997. The median follow-up period was 55 months. Treatment strategies differed according to lesion type, topography, and size, as well as visibility of the fifth cranial nerve in the prepontine cistern. Three different treatment groups were established. When the primary goal was treatment of the lesion (Group IV, 46 patients) we obtained pain cessation in 79.5% of cases. In some patients in whom GKS was not indicated for treatment of the lesion, TN was treated by targeting the fifth nerve directly in the prepontine cistern if visible (Group II, three patients) or in the part of the lesion including this nerve if the nerve root could not be identified (Group III, four patients). No deaths and no radiosurgically induced adverse effects were observed, but in two cases there was slight hypesthesia (Group IV). The neuropathic component of the facial pain appeared to be poorly sensitive to radiosurgery. At the last follow-up examination, six patients (13.3%) exhibited recurrent pain, which was complete in four cases (8.8%) and partial in two (4.4%). CONCLUSIONS: The results of GKS regarding facial pain control are very similar to those achieved by microsurgery according to series published in the literature. Nevertheless, the low rate of morbidity and the greater comfort afforded the patient render GKS safer and thus more attractive. PMID- 11780890 TI - Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients. AB - OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa. PMID- 11780889 TI - Surgical anatomy of the cerebral arteries in patients with subarachnoid hemorrhage: comparison of computerized tomography angiography and digital subtraction angiography. AB - OBJECT: The purpose of this study was to compare computerized tomography (CT) angiography and digital subtraction (DS) angiography studies in patients with subarachnoid hemorrhage (SAH) to assess their vascular anatomy relevant to cerebral aneurysm surgery. METHODS: From a prospective series of 100 patients with SAH, the authors selected 73 patients whose CT angiography studies were of adequate quality and in whom DS angiography of both carotid arteries had been performed. Eleven patients with no DS angiographic studies of the vertebrobasilar artery were only evaluated for the anterior half of the circle of Willis. Anterior communicating arteries (ACoAs), both precommunicating anterior cerebral arteries (A1 segments), both posterior communicating arteries (PCoAs), and both precommunicating posterior cerebral arteries (P1 segments) were assessed on CT angiography and DS angiography by two independent observers. CONCLUSIONS: Computerized tomography angiography compares well with DS angiography for visualizing normal-sized arteries, and is superior for visualizing ACoAs and hypoplastic A1 and P, segments. Important preoperative aspects such as dominant A1 segments and PCoAs are equally well seen using either modality. Neither method enabled the authors to visualize more than 50% of PCoAs. Use of CT angiography can provide the required preoperative anatomical information for aneurysm surgery in most patients with SAH. PMID- 11780892 TI - Diagnosis and management of pituitary abscess: a review of twenty-four cases. AB - OBJECT: Pituitary abscess is a rare but serious intrasellar infection. To better determine the salient signs and symptoms that help in making the diagnosis, and to determine the most appropriate treatment, the authors reviewed their experience in a series of 24 patients treated at the University of California at San Francisco. METHODS: Nine of the patients were female and 15 were male, and their mean age was 41.2 years (range 12-71 years). Surprisingly, most patients in our series presented with complaints and physical findings consistent with a pituitary mass, but rarely with evidence of a serious infection. Headache, endocrine abnormalities, and visual changes were the most common clinical indicators; fever, peripheral leukocytosis, and meningismus were present in 33% or fewer of the patients. Imaging tests demonstrated a pituitary mass in all patients, but the features evident on computerized tomography and magnetic resonance studies did not distinguish pituitary abscesses from other, more common intrasellar lesions. Because of the ambiguous clinical features and imaging findings, most abscesses were not diagnosed before treatment; rather, the diagnosis was made during surgical exploration of the sella turcica, when the surgeon encountered a cystic mass containing pus. There were only two deaths in this series (8.3%). Patients presenting with headache and visual changes noted improvement in almost all cases; patients with endocrine dysfunction generally did not recover normal pituitary function, but were easily treated with hormone replacement therapy. CONCLUSIONS: Antibiotic therapy is suggested for patients who have symptoms of sepsis, or for patients in whom specific organisms are identified from cultures obtained during surgery. The transsphenoidal approach is recommended over open craniotomy for surgical drainage. PMID- 11780891 TI - Carbon dioxide reactivity, pressure autoregulation, and metabolic suppression reactivity after head injury: a transcranial Doppler study. AB - OBJECT: Contemporary management of head-injured patients is based on assumptions about CO2 reactivity, pressure autoregulation (PA), and vascular reactivity to pharmacological metabolic suppression. In this study, serial assessments of vasoreactivity of the middle cerebral artery (MCA) were performed using bilateral transcranial Doppler (TCD) ultrasonography. METHODS: Twenty-eight patients (mean age 33 +/- 13 years, median Glasgow Coma Scale score of 7) underwent a total of 61 testing sessions during postinjury Days 0 to 13. The CO2 reactivity (58 studies in 28 patients), PA (51 studies in 23 patients), and metabolic suppression reactivity (35 studies in 16 patients) were quantified for each cerebral hemisphere by measuring changes in MCA velocity in response to transient hyperventilation, arterial blood pressure elevation, or propofol-induced burst suppression, respectively. One or both hemispheres registered below normal vasoreactivity scores in 40%, 69%, and 97% of study sessions for CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.0001), respectively. Intracranial hypertension, classified as intracranial pressure (ICP) greater than 20 mm Hg at the time of testing, was associated with global impairment of CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.05). A low baseline cerebral perfusion pressure (CPP) was also predictive of impaired CO2 reactivity and PA (p < 0.01). Early postinjury hypotension or hypoxia was also associated with impaired CO2 reactivity (p < 0.05), and hemorrhagic brain lesions in or overlying the MCA territory were predictive of impaired metabolic suppression reactivity (p < 0.01). The 6-month Glasgow Outcome Scale score correlated with the overall degree of impaired vasoreactivity (p < 0.05). CONCLUSIONS: During the first 2 weeks after moderate or severe head injury, CO2 reactivity remains relatively intact, PA is variably impaired, and metabolic suppression reactivity remains severely impaired. Elevated ICP appears to affect all three components of vasoreactivity that were tested, whereas other clinical factors such as CPP, hypotensive and hypoxic insults, and hemorrhagic brain lesions have distinctly different impacts on the state of vasoreactivity. Incorporation of TCD ultrasonography-derived vasoreactivity data may facilitate more injury- and time specific therapies for head-injured patients. PMID- 11780893 TI - Surgery for temporal lobe epilepsy in older patients. AB - OBJECT: The goal of this study was to evaluate the efficacy of surgery for temporal lobe epilepsy (TLE) in older (> or = 50 years of age) patients. METHODS: The authors conducted a review of all patients 50 years of age or older with TLE surgically treated at the Montreal Neurological Institute and Hospital since 1981 by one surgeon (A.O.). Only patients without a mass lesion were included. Outcome parameters were compared with those of younger individuals with TLE, who were stratified by age at operation. In patients aged 50 years and older, the onset of complex partial seizures occurred 5 to 53 years (mean 35 years) prior to the time of surgery. Postoperatively, over a mean follow-up period of 64 months, 15 patients (83%) obtained a meaningful improvement, becoming either free from seizures or only experiencing a rare seizure. Most surgery outcomes were similar in both older and younger individuals, except for a trend to more freedom from seizures and increased likelihood of returning to work or usual activities in the younger patients. Note that a patient's long-standing seizure disorder did not negatively affect their ability to achieve freedom from seizures following surgery. CONCLUSIONS: Surgery for TLE appears to be effective for older individuals, comparing favorably with results in younger age groups, and carries a small risk of postoperative complications. PMID- 11780894 TI - Subduroperitoneal drainage for subdural hematomas in infants: results in 244 cases. AB - OBJECT: Subduroperitoneal drainage (SDPD) is commonly used in the treatment of infantile subdural hematomas (SDHs). Few studies have focused on this technique and most series have included SDHs of various origins in children of different ages. The surgical procedure is not standardized and results achieved using this technique have not been well documented. The authors reviewed their cases of traumatic SDH treated with SDPD in infants (< 2 years of age). Their standard technique includes bilateral SDPD whenever the SDH is bilateral, placement of a free shunt, and systematic removal of the drainage unit after a few months. METHODS: The authors performed SDPD in 244 infants with traumatic SDH. The patients' SDHs were controlled by SDPD in 241 cases, and 78.9% of the patients recovered to live a normal life. Complications of SDPD occurred in 38 patients (15.6%): obstruction in 22 cases (9%), infection in eight cases (3.28%), and internal hydrocephalus in eight cases (3.28%). Early complications could be ascribed to surgical technique, delayed complications were associated with the severity of the initial clinical presentation, and late complications were time dependent and unrelated to initial clinical severity. Poor clinical outcome was correlated to the severity of the initial presentation, but not to complications of surgery. CONCLUSIONS: Because of its efficacy and low complication rate, SDPD is the procedure of choice when subdural taps fail to control SDH. The authors prefer bilateral drainage because of the low rate of complications. Drains should be systematically removed after a few months to prevent long-term complications. PMID- 11780895 TI - Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. AB - OBJECT: Factors affecting the postoperative recurrence of chronic subdural hematomas (CSDHs) have not been sufficiently investigated. The authors have attempted to determine features of CSDHs that are associated with a high or low recurrence rate on the basis of the natural history of these lesions and their intracranial extension. METHODS: One hundred six patients (82 men and 24 women) harboring 126 CSDHs who were treated at Tokyo Kosei Nenkin Hospital between January 1989 and April 1998 were studied. Types of CSDHs were classified according to hematoma density and internal architecture, and the intracranial extension of the hematomas were investigated. The postoperative recurrence rate was calculated for each factor. Based on the internal architecture and density of each hematoma, the CSDHs were classified into four types, including homogeneous, laminar, separated, and trabecular types. The recurrence rate associated with the separated type was high, whereas that associated with the trabecular type was low. Chronic subdural hematomas are believed to develop initially as the homogeneous type, after which they sometimes progress to the laminar type. A mature CSDH is represented by the separated stage and the hematoma eventually passes through the trabecular stage during absorption. Based on the intracranial extension of each hematoma, CSDHs were classified into three types, including convexity, cranial base, and interhemispheric types. The recurrence rate of cranial base CSDHs was high and that of convexity CSDHs was low. CONCLUSIONS: Classification of CSDHs according to the internal architecture and intracranial extension may be useful for predicting the risk of postoperative recurrence. PMID- 11780896 TI - Role of dural fenestrations in acute subdural hematoma. AB - OBJECT: Patients with acute subdural hematomas (ASDHs) have higher mortality and lower functional recovery rates compared with those of other head-injured patients. Early surgical decompression and active intensive care treatment represent, so far, the best way to assist these patients. Paradoxically, one of the factors contributing to poor outcomes in cases of ASDHs could be rapid surgical decompression, owing to the severe extrusion of the brain through the craniotomy defect in response to acute brain swelling. To avoid the deleterious consequences of abrupt decompression of the subdural space with disruption of brain tissue, the authors have adopted a new surgical technique for evacuation of ASDHs. This procedure consists of creating multiple fenestrations of the dura (MFD) in a meshlike fashion and removing clots through the small dural openings that are left open, avoiding the creation of a wide dural opening and the disruption of and additional damage to brain tissue. METHODS: Thirty-one patients (26 male and five female patients with a mean age of 32.5 years) harboring ASDHs were treated using this method. On admission there were 16 patients (51.5%) with Glasgow Coma Scale (GCS) scores of 3 to 5, 11 patients (35.5%) with GCS scores of 6 to 8, and four patients (12.9%) with GCS scores of 9 to 12. Postoperative computerized tomography scans of the brain revealed evacuation of more than 80% of the hematoma in 29 of 31 patients. The overall mortality rate in this group was 51.6%. CONCLUSIONS: This preliminary report of a new surgical approach for patients who have sustained ASDHs should be considered to avoid abrupt disruption of the brain and to allow the gradual and gentle release of subdural clots. This is especially important in cases in which there are severe midline shifts and a tight brain. Further clinical studies should be conducted in a more selected series to estimate the impact of this new procedure on morbidity and mortality rates. PMID- 11780897 TI - Surgery on a saccular vertebral artery-posterior inferior cerebellar artery aneurysm via the transcondylar fossa (supracondylar transjugular tubercle) approach or the transcondylar approach: surgical results and indications for using two different lateral skull base approaches. AB - OBJECT: The authors report on the surgical results they achieved in caring for patients with vertebral artery-posterior inferior cerebellar artery (VA-PICA) saccular aneurysms that were treated via either the transcondylar fossa (supracondylar transjugular tubercle) approach or the transcondylar approach. In this report they clarify the characteristics of and differences between these two lateral skull base approaches. They also present the techniques they used in performing the transcondylar fossa approach, especially the maneuver used to remove the jugular tubercle extradurally without injuring the atlantooccipital joint. METHODS: Eight patients underwent surgery for VA-PICA saccular aneurysms (six ruptured and two unruptured ones) during which one of the two approaches was performed. Clinical data including neurological and radiological findings and reports of the operative procedures were analyzed. The Glasgow Outcome Scale was used to estimate the activities of daily living experienced by the patients. In all cases the aneurysm was successfully clipped and no permanent neurological deficits remained, except for one case of severe vasospasm. In seven of the eight patients, the transcondylar fossa approach provided a sufficient operative field for clipping the aneurysm without difficulty. In the remaining patient, in whom the aneurysm was located at the midline on the clivus at the level of the hypoglossal canal, the aneurysm could not be found by using the transcondylar fossa approach; thus, the route was changed to the transcondylar approach, and clipping was performed below the hypoglossal nerve rootlets. CONCLUSIONS: Both approaches offer excellent visualization and a wide working field, with ready access to the lesion. This remarkably reduces the risk of development of postoperative deficits. These approaches should be used properly; the transcondylar fossa approach is indicated for aneurysms located above the hypoglossal canal and the transcondylar approach is indicated for those located below it. PMID- 11780898 TI - Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease. AB - OBJECT: There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. METHODS: Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the "on" or "off' phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. CONCLUSIONS: Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits. PMID- 11780899 TI - Transsphenoidal surgery and adjuvant gamma knife treatment for growth hormone secreting pituitary adenoma. AB - OBJECT: The results of combined transsphenoidal surgery and adjuvant gamma knife surgery (GKS) for growth hormone (GH)-secreting adenoma were investigated using biochemical cure criteria for surgery and biological cure criteria for adjuvant GKS. METHODS: Ninety patients (42 male and 48 female patients), ranging from 11 to 75 years of age, underwent transsphenoidal surgery for GH-secreting pituitary adenoma. Preoperative and postoperative GH and insulin-like growth factor-I levels were measured, as was the postoperative GH level after the oral glucose tolerance test. Tumor size, cavernous sinus (CS) invasion, and residual tumor were evaluated using magnetic resonance (MR) imaging. Transsphenoidal microsurgery was performed, followed by adjuvant GKS when there was persistent biochemical evidence of GH hypersecretion with residual tumor detectable in the CS on MR imaging. Patients in whom GKS was contraindicated were treated with conventional radiotherapy or by medical means. CONCLUSIONS: The overall surgical cure rate was 57% based on recently accepted biochemical cure criteria. Patients with no CS invasion achieved a 100% cure rate, whereas patients with CS invasion achieved an 82% cure rate (14 of 17 patients) after adjuvant GKS. The combination of transsphenoidal microsurgery and adjuvant GKS is the optimal therapy for patients with GH-secreting adenoma. PMID- 11780900 TI - Diagnostic value of 201Tl-single-photon emission computerized tomography studies in cases of posterior fossa hemangioblastomas. AB - OBJECT: The 201Tl uptake index was evaluated for its usefulness in formulating a diagnosis of hemangioblastoma. Thallium-201-single-photon emission computerized tomography (SPECT) studies were performed in nine patients harboring hemangioblastomas in the posterior fossa and in five patients (six lesions) with gliomas in the posterior fossa. METHODS: The 201Tl uptake index was defined as the ratio of mean counts of isotope per pixel in the tumor to mean counts of isotope per pixel in the homologous region of the healthy brain. The 201Tl uptake indices of the early image (TlE) and that of the delayed image (TlD) were calculated. The isotope retention index (RI) was calculated as (TlE - TlD)/TlE. The TlE was 2.7 +/- 0.7 in hemangioblastomas and 2.9 +/- 1.7 in gliomas (mean +/- standard deviation). The TlD was 1.5 +/- 0.4 in hemangioblastomas and 2.4 +/- 1.6 in gliomas. There were no significant differences between hemangioblastomas and gliomas when TlEs and TlDs were compared. The isotope RI was 0.43 +/- 0.07 in hemangioblastomas and 0.15 +/- 0.1 in gliomas, showing a significantly higher RI in hemangioblastomas compared with gliomas (p < 0.01). CONCLUSIONS: Thallium-201 washout is significantly faster in hemangioblastomas. Hemangioblastoma is biologically benign, but contains a rich capillary network that forms a hypervascular tumor bed. Variations in its appearance on magnetic resonance images may cause difficulties in the differential diagnosis of hemangioblastoma. Thallium-201 SPECT studies can be used to distinguish hemangioblastomas from gliomas in the posterior fossa. PMID- 11780901 TI - A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein-13 adenoviral gene therapy. AB - OBJECT: Bone morphogenetic proteins (BMPs) are involved in the growth and development of many tissues, but it is their role in skeletal development and their unique ability to induce ectopic and orthotopic osteogenesis that have attracted the greatest interest. Expression of the BMP-13 gene is predominantly localized to hypertrophic chondrocytes in regions of endochondral bone formation during development, as well as in mature articular cartilage in the adult. In addition, the application of BMP-13 on a collagen carrier induces neotendon/neoligament formation when delivered subcutaneously or intramuscularly in rodents. The aim of the present study was to determine the histological and ultrastructural changes that occur after the intramuscular injection of a first generation BMP-13 adenoviral vector. METHODS: Athymic nude rats were injected with 3.75 x 10(10) plaque-forming units of adenovirus (Ad)-BMP-13 or Ad-beta galactosidase in the thigh musculature, and the region was examined using light and electron microscopy at various time points between 2 days and 100 days postinjection. As early as 2 days after injection of Ad-BMP-13, progenitor cells were observed infiltrating between the transduced muscle fibers. These cells subsequently proliferated, differentiated, and secreted large amounts of collagenous extracellular matrix. By 100 days postinjection, the treated tissue displayed the histological and ultrastructural appearance of neotendon/neoligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the treated tissue. A short-term bromodeoxyuridine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection. At all time points, the control AD-beta-gal injection sites were found to contain only normal muscle, without evidence of inflammation or mesenchymal cell proliferation. CONCLUSIONS: The results of this study indicate that in the future the use of the BMP-13 gene may have therapeutic utility for the healing of tendon and ligament tears and avulsion injuries. PMID- 11780902 TI - Transplantation of human fetal brain cells into ischemic lesions of adult gerbil hippocampus. AB - OBJECT: The goal of this study was to establish whether transplanted cells derived from fetal human brain can survive in an ischemic lesion. METHODS: Sixteen adult male Mongolian gerbils underwent transient bilateral common carotid artery occlusion. One week later, cell suspensions prepared from fetal human brain were injected using stereotactic guidance into the CA1 region of the hippocampus on one side. On the contralateral side injection of the cell suspension medium only was performed. One week after transplantation, the animals were perfusion fixed and their brains were processed for histological studies as well as expression of neuron and glia-specific antigens. Data from ischemic animals were compared with eight nonischemic gerbils that served as sham-operated controls. Last, the in vivo data were correlated with observations made from matching in vitro cultures of the fetal brain cell suspension. The in vivo data indicated that transplanted human fetus-derived brain cells survived in ischemic lesions of gerbil hippocampus after 1 week, provided that the host animal underwent adequate immunosuppression and the transplanted cells were not incorporated into the scar caused by the transplantation procedure. Unlike their in vivo counterparts, after 1 week, most cultured fetal brain cells expressed either neuron- or astrocyte-specific antigens. CONCLUSIONS: This work demonstrates that xenotransplanted fetal human brain cells are able to survive in an ischemic lesion in a rodent model. These data might be useful for future neural transplantation studies of treatments for cerebrovascular ischemia in humans. PMID- 11780903 TI - Neural regeneration along longitudinal polyglactin sutures across short and extended defects in the rat sciatic nerve. AB - OBJECT: The authors have previously shown that longitudinal sutures without artificial tube support regeneration across a 7-mm gap in the rat sciatic nerve. In the present study, the authors compared this new approach with the use of autologous nerve grafts across short defects and examined whether the approach could be used to support regeneration across extended gaps and whether the interposition of a short nerve segment (the stepping-stone procedure) was applicable in this model. METHODS: Longitudinal sutures were used to bridge 7- and 15-mm gaps in the rat sciatic nerve. Contralateral comparisons were made to nerve autografts in the 7-mm group and to sutures plus a short interposed nerve segment in the 15-mm group. Regeneration was evaluated at 2, 4, and 12 weeks by using immunocytochemical analysis for Schwann cells, neurofilament protein, and macrophages and at 12 weeks also by using histological examination, including morphometry in the distal tibial trunk and tetanic force measurements in the gastrocnemius muscle. CONCLUSIONS: The authors found that the results of regeneration after repair with longitudinal polyglactin sutures across short defects were not significantly different from those produced by the use of autologous nerve grafts. Regeneration, although poor, occurred along sutures across extended gaps and was significantly enhanced by an interposed nerve segment acting as a Schwann cell resource in this model. PMID- 11780904 TI - Neuroimaging of cerebellar liponeurocytoma. Case report. AB - Cerebellar liponeurocytoma is a newly recognized, rare clinicopathological entity. It manifests with posterior fossa symptoms in adults and is characterized histopathologically by advanced neuronal and focal lipomatous differentiation with a low level of mitotic activity. The authors analyzed the computerized tomography (CT) and magnetic resonance (MR) imaging findings in two patients with histopathologically proven cerebellar liponeurocytomas and review the literature. Cerebellar liponeurocytoma may be suspected on the basis of neuroimaging findings that demonstrate an intraaxial neoplasm with the propensity for exophytic growth into the adjacent subarachnoid spaces. On CT scans, the tumor commonly presents as a hypointense mass with intermingled areas exhibiting the attenuation values of fatty tissue. On T1-weighted MR images, the tumor is hypointense with scattered foci of hyperintense signal and displays moderate contrast enhancement. On T1-weighted MR images, the tumor is slightly hyperintense to cortex, and edema is usually absent. Areas of fat density as assessed on CT scans and of T1 hyperintensity seen on MR images help to distinguish this rare neoplasm from the more common adult medulloblastomas or ependymomas. The available follow-up data indicate a favorable clinical prognosis; therefore, knowledge and precise characterization of this tumor is important to avoid unnecessary adjuvant radio- or chemotherapy. PMID- 11780905 TI - Aggressive fibromatosis (desmoid tumor) of the radial nerve: favorable resolution. Case report. AB - Aggressive fibromatosis (desmoid tumor) of a peripheral nerve is a rarity. Isolated cases have been reported in which the tumor originated from neighboring structures and only secondarily invaded the nerves. The case described in this report is unusual because the tumor selectively invaded the patient's nerve fascicles, requiring removal and graft repair. The procedure was followed by an excellent clinical recovery and no recurrence as of the 6-year follow-up review. PMID- 11780906 TI - Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report. AB - The authors report the case of a 37-year-old woman who presented with amenorrhea and an increased level of serum prolactin. Magnetic resonance images of the pituitary revealed a lesion with characteristics consistent with those of a microadenoma. Transsphenoidal exploration was performed, but a prolactinoma was not found. After endocrinological review, the patient's hyperprolactinemia was found to be caused by the presence of macroprolactin and her amenorrhea was due to intense exercise and low body weight. Macroprolactin is an isoform of prolactin that is variably reactive in assays for prolactin, but displays minimum bioactivity in vivo. Patients with macroprolactin are mostly asymptomatic. This phenomenon may cause elevated prolactin values, which the authors view as apparent hyperprolactinemia. The presence of macroprolactin is an underrecognized problem, occurring in as many as 15 to 20% of patients with elevated prolactin values and often leading to unnecessary, expensive diagnostic procedures and inappropriate treatment. The presence of macroprolactin should always be suspected when the patient's clinical history or clinical or radiological data are incompatible with the prolactin value. Physicians dealing with diagnosis and treatment of hyperprolactinemia (general practitioners, gynecologists, neurosurgeons, endocrinologists, and biochemists) should be aware of the potentially misleading nature of macroprolactin. PMID- 11780907 TI - Segmental myoclonus as the sole manifestation of a choroid plexus papilloma in the posterior fossa. Case report. AB - The authors describe the case of a 22-year-old woman with involuntary contractions of the sternocleidomastoid and trapezius muscles that resulted in turning movements of the head. The jerks displayed the clinical and neurophysiological characteristics of segmental myoclonus (SM) restricted to muscles supplied bilaterally by the first four cervical segments. Magnetic resonance imaging disclosed a tumor in the midline above the cisterna magna that was later histologically proven to be a choroid plexus papilloma. The patient's involuntary movements did not extend to other muscle groups or, in particular, to the palate, as one might have expected in the case of brainstem lesions. Myoclonus was the sole clinical manifestation of the tumor in this patient; other signs and symptoms invariably reported in other cases of posterior fossa papilloma, such as increased intracranial pressure or cranial nerve palsies, were absent. Release from suprasegmental control is suggested as a possible pathophysiological mechanism in this case of SM. PMID- 11780908 TI - Recurrence of a neurenteric cyst with malignant transformation in the foramen magnum after total resection. Case report. AB - A 53-year-old man presented with recurrence of a neurenteric cyst with malignant transformation in the foramen magnum 3.5 years after total resection of the original tumor had been reported. For 2 years following the initial surgery, the patient had been in good condition, but then underwent ventriculoperitoneal shunt placement for intracranial hypertension. At the time there was no evidence of recurrence of the tumor on magnetic resonance (MR) images. One and one-half years later, he presented with headache and anorexia. A massive recurrent tumor was identified on MR images. The tumor was severely adhesive to the brainstem, cranial nerves, and vessels, allowing only partial resection. Histological examination of tumor specimens obtained during the first and second craniotomies indicated a malignant change from a typical neurenteric cyst with a one-layer epithelium in the first specimen to an adenocarcinoma with papillary proliferation in the second. The results of various immunohistochemical studies of the first specimen were typical of those of a neurenteric cyst. The second specimen displayed stronger staining of carbohydrate 19-9 and carcinoembryonic antigens than the initial specimen. The percentage of Ki-67 antigen (MIB-1) positive cells increased from 0% in the first specimen to 6.7% in the second. To the authors' knowledge this is the first case in which malignant transformation has been demonstrated after total resection of a neurenteric cyst in the foramen magnum. PMID- 11780909 TI - Associated arteriovenous malformation of the orbit and brain: a case of Wyburn Mason syndrome without retinal involvement. Case report. AB - Wyburn-Mason syndrome is a rare condition associated with multiple cerebral arteriovenous malformations. The disease, also called retinoencephalofacial angiomatosis, includes lesions of the retina, brain, and skin. This disorder stems from a vascular dysgenesis of the embryological anterior plexus early in the gestational period when the primitive vascular mesoderm is shared by the involved structures. The timing of the insult to the embryonic tissue determines which structures are affected. Extensions of the lesions vary widely but cutaneous lesions are unusual. Among reports in the literature, only three cases appear to have manifested without retinal involvement. The authors report the fourth case of Wyburn-Mason syndrome in which there was no retinal involvement and the first to involve neither the retina nor the face. PMID- 11780910 TI - Ossification of autologous pericranium used in duraplasty. Case report. AB - Pericranium is frequently used in duraplasty and is considered superior to the many other alternatives because of its easy availability and because it offers a watertight dural closure while minimizing the problems of adhesion, infection, and rejection. Although the osteogenic potential of all periosteal tissues is recognized, a review of the literature did not reveal a reported case of osseous formation following use of pericranium for duraplasty. The authors report the case of a 17-year-old man who presented with a self-inflicted gunshot wound to the head. He was obtunded, but moving all extremities purposefully. Computerized tomography scanning demonstrated bifrontal injury. A bicoronal craniotomy with debridement was performed on an emergency basis, with vascularized pericranium used for a duraplasty. Follow-up cranioplasty demonstrated significant ossification of the pericranium 5 months after the original surgery. Pericranium is an attractive material for duraplasty; however, its osteogenic potential may interfere with future cranioplasty and cosmesis. This may be especially relevant in young persons. PMID- 11780911 TI - Balloon angioplasty to treat vasospasm after transsphenoidal surgery. Case illustration. PMID- 11780912 TI - No ordinary time, no ordinary men: the relationship between Harvey Cushing and Franklin D. Roosevelt, 1928-1939. AB - The authors elucidate the strong personal relationship that developed between Dr. Harvey Cushing and Franklin Delano Roosevelt (FDR) from 1928 to 1939, as manifested in their frequent letters to each other. The relationship was initiated by the marriage of their children. Through his correspondence with FDR, Cushing was able to affect several medical issues of the period. The relationship of these two individuals is set within the historical, social, and political contexts of the times. PMID- 11780913 TI - Right temporal lobe function. PMID- 11780914 TI - Cerebrospinal fluid leak after acoustic surgery. PMID- 11780915 TI - Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. AB - The aim of the present prospective study was to determine whether subtle sperm morphological characteristics affect the outcome of intracytoplasmic sperm injection (ICSI), and if so, to identify those that are relevant. For this purpose, we developed a new method, the motile sperm organelle morphology examination (MSOME). The examination is performed in real time using an inverted light microscope equipped with high-power Nomarski optics enhanced by digital imaging to achieve a magnification up to 6300x. MSOME was applied to the leftover sperm fraction selected for microinjection in 100 random couples referred for ICSI treatment at 3 major in vitro fertilization centers. We found that the morphological normalcy of the entire sperm cell, according to MSOME criteria, was positively associated with ICSI fertilization rate (area under the receiver operating characteristics [ROC] curve, 88%) but not with pregnancy outcome. The morphological normalcy of the sperm nucleus, defined by MSOME, was significantly and positively associated with both fertilization rate and pregnancy outcome (areas under the ROC curve, 72% and 74%, respectively). These findings indicate that ICSI-associated pregnancy rate may be affected by subtle morphological malformations of the sperm nucleus, which may remain undetected by the embryologist during the routine selection procedure. PMID- 11780916 TI - Detection of DNA damage in response to cooling injury in equine spermatozoa using single-cell gel electrophoresis. AB - Single-cell gel electrophoresis (SCGE), or comet assay, has the ability to detect damage at the single cell level and has not been reported for equine sperm. The ability to detect nuclear damage at the single cell level could aid in the advancement of protocols for optimal semen preservation. The goals of these experiments were to adapt this assay for use with equine sperm and to utilize the assay for determining the integrity of equine sperm DNA following treatments with storage at various decreased temperatures (-20 degrees C and 5 degrees C). Results from experiments in which sperm were frozen (-20 degrees C) in the absence of cryoprotectants revealed that significantly more cells with fragmented tails of DNA, or comets, occurred among those exposed to 1, 3, and 5 freeze-thaw cycles (65% +/- 6%, 76% +/- 11%, 92% +/- 6%, respectively) compared with fresh, untreated sperm (19% +/- 16%, P < .05). In addition DNA damage was different (P < .05) between the three freeze-thaw treatments. Sensitivity of SCGE on equine sperm was further tested with known ratios of frozen-thawed and fresh cells. The amount of detectable DNA damage was positively correlated with the percentage of cryo-damaged cells in each treatment (r2 = 0.92, P < .05). Potential damage as a result of cooled storage was also investigated and results revealed that sperm stored for 48 hours (at 5 degrees C) had a higher percentage of comets than that of fresh sperm (63% +/- 13.9% and 28% +/- 15.6%, respectively, P < .05). The percentage of viable sperm also decreased linearly over time and was inversely correlated with percent of comets (r2 = 0.805, P < .001). Detection of sublethal and/or uncompensable fertility factors in semen, such as DNA fragmentation, could be useful for detecting male differences in semen for cooling or cryopreservation potential and could provide a tool for monitoring and preserving fertility for individual stallions. PMID- 11780917 TI - Protein kinase C increases 11beta-hydroxysteroid dehydrogenase oxidation and inhibits reduction in rat Leydig cells. AB - Glucocorticoid hormone controls Leydig cell steroidogenic function through a receptor-mediated mechanism. The enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD) plays an important role in Leydig cells by metabolizing glucocorticoids, and catalyzing the interconversion of corticosterone (the active form in rodents) and 11-dehydrocorticosterone (the biologically inert form). The net direction of this interconversion determines the amount of biologically active ligand, corticosterone, available for glucocorticoid receptor binding. We hypothesize that 11betaHSD oxidative and reductive activities are controlled separately in Leydig cells, and that shifts in the favored direction of 11betaHSD catalysis provide a mechanism for the control of intracellular corticosterone levels. Therefore, in the present study, we tested the dependency of 11betaHSD oxidative and reductive activities on protein kinase C (PKC) and calcium dependent signaling pathways. 11betaHSD oxidative and reductive activities were measured in freshly isolated intact rat Leydig cells using 25 nM radiolabeled substrates after treatment with protein kinase modulators. We found that PKC and calcium-dependent signaling had opposing effects on 11betaHSD oxidative and reductive activities. Stimulation of PKC using the PKC activator, 6-[N decylamino]-4-hydroxymethylinole (DHI), increased 11betaHSD oxidative activity from a conversion rate of 5.08% to 48.23% with an EC50 of 1.70 +/- 0.44 microM (mean +/- SEM), and inhibited reductive activity from 26.90% to 3.66% conversion with an IC50 of 0.22 +/- 0.05 microM. This indicated that PKC activation in Leydig cells favors 11betaHSD oxidation and lower levels of corticosterone. The action of DHI was abolished by the PKC inhibitor bisindolylmaleimide I. In contrast, addition of calcium to Leydig cells increased 11betaHSD reductive activity while decreasing oxidative activity, thereby favoring reduction and conversion of inert 11-dehydrocorticosterone into active corticosterone. The opposite effect was seen after elimination of calcium-dependent signaling, including removal of calcium by EGTA or addition of the calmodulin (calcium binding protein) inhibitor SKF7171A, or the calcium/calmodulin-dependent protein kinase I (CaMK II) inhibitor, KN62. We conclude that 11betaHSD oxidative and reductive activities are separately regulated and that, in contrast to calcium dependent signaling, PKC stimulates 11betaHSD oxidation while inhibiting 11betaHSD reduction. Maintenance of a predominantly oxidative 11betaHSD could serve to eliminate adverse glucocorticoid-induced action in Leydig cells. PMID- 11780918 TI - Cytogenetic investigations of infertile men with low sperm counts: a 25-year experience. PMID- 11780919 TI - Are we ready for cloning? PMID- 11780920 TI - Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. PMID- 11780921 TI - Andropause and testosterone supplementation for cognitive loss. PMID- 11780922 TI - As the number of treatment modalities for erectile dysfunction broadened to include the use of an effective oral pharmacologic agent, the surgical implantation of penile prostheses declined. PMID- 11780923 TI - Localization of the sperm protein SP22 and inhibition of fertility in vivo and in vitro. AB - We previously established that levels of the sperm membrane protein, SP22, are highly correlated with the fertility of sperm from the cauda epididymidis of rats exposed to both epididymal and testicular toxicants, and that a testis-specific SP22 transcript is expressed in postmeiotic germ cells. In this study, polyclonal and monoclonal antibodies were generated to study the expression of SP22 in the testis and epididymis, and to determine whether SP22 plays a coincidental or causal role in fertility. Polyclonal antiserum was raised in sheep against full length recombinant rat SP22 (rSP22). Hybridoma clones were generated from mice immunized with rSP22 and boosted with native SP22; positive clones were used for ascites production. Immunoblots indicated that affinity-purified anti-rSP22 immunoglobulin (Ig) and ascites Ig recognized denatured and native SP22, respectively. Linear epitope mapping of the 189-amino acid SP22 sequence revealed 3 distinct peptide sequences recognized by anti-rSP22 Ig, and 1 sequence recognized by ascites Ig. Cytoplasm of round spermatids and heads of elongating/elongated spermatids immunostained with both anti-rSP22 and ascites antibodies. Isolated rete testis sperm revealed discrete staining over the cytoplasmic droplet, whereas staining was apparent over the equatorial segment of the head by the time sperm reached the caput epididymidis. Clear cells were, interestingly, immunostained along the length of the epididymis. Ascites Ig and anti-SP22 Ig each recognized the equatorial segment of sperm heads from rat, hamster, bull, rabbit, and human. Ascites Ig and affinity-purified anti-rSP22 Ig each significantly inhibited the fertility of cauda epididymal sperm from the rat in vivo, as well as the fertilization rates of cauda epididymal sperm in vitro. Moreover, affinity-purified anti-rSP22 significantly inhibited in vitro fertilization of both zona-intact and zona-free hamster oocytes, suggesting that SP22 may play a role in both the zona penetration and membrane fusion steps of fertilization. PMID- 11780924 TI - P53 and Fas are sequential mechanisms of testicular germ cell apoptosis. AB - Testicular germ cell apoptosis in the cryptorchid testis is induced by abdominal heat stress. p53-dependent apoptosis appears responsible for the initial phase of germ cell loss in experimental cryptorchidism based on a 3-day delay of apoptosis in p53-/- mice. However, the mechanisms underlying the subsequent p53-independent apoptosis have not been identified. Although studies have suggested that Fas plays a role in testicular germ cell apoptosis, no direct evidence has been shown. To test the hypothesis that Fas is involved in testicular germ cell apoptosis and is responsible for the p53-independent phase of apoptosis in the cryptorchid testis, p53-/-, lpr/lpr (a spontaneous mutation in the Fas gene, which causes autoimmune disease) double-mutant mice were generated and unilateral cryptorchidism was induced in these mice. It was found that testicular weight reduction and germ cell apoptosis were delayed by an additional 3 days, and the Fas production increased in the time frame of p53-independent apoptosis in the experimental cryptorchid testis of wild-type mice. These results suggest that Fas is involved in testicular germ cell apoptosis, and that Fas-dependent apoptosis is responsible for the p53-independent phase of germ cell apoptosis in the cryptorchid testis. The cascade of testicular germ cell apoptosis in response to heat stress implies the existence of sequential quality control mechanisms in spermatogenesis. PMID- 11780925 TI - Sperm cryopreservation for men with nonmalignant, systemic diseases: a descriptive study. AB - Cytotoxic drugs and immunosuppressive therapies are used to treat patients with nonmalignant, nontesticular systemic diseases. These therapies can permanently suppress spermatogenesis. Sperm cryopreservation before treatment theoretically could give these men the opportunity to achieve a pregnancy with a woman later in life when the couple decides to do so. However, it is not known whether pretreatment sperm quality in these men is good enough to be used for assisted reproductive techniques. The main objective of this study was to determine the usefulness of cryopreservation in this patient population by: 1) assessing their pretreatment semen quality (eg, count, motility, and motion kinetics) and comparing it with that of healthy donors before and after cryopreservation; 2) comparing patients' pretreatment semen characteristics with World Health Organization reference values for normal sperm; and 3) examining the differences in semen parameters among patient groups. Semen specimens were obtained from 25 healthy donors and from 23 patients with a variety of disorders (12 had autoimmune disorders, 4 had kidney disorders, 3 had diabetes, 2 had ulcerative colitis, and 2 had heart transplants). All patients, except those with diabetes, required immunosuppressive or cytotoxic therapy. Although the pretreatment quality of the semen of these patients was not as good as that of donors, semen samples were within the normal reference range of the World Health Organization. No statistically significant differences in sperm parameters were found within the 4 patient groups except for those with diabetes (n = 3), who showed poorer sperm counts (P < .04). However, no conclusive evidence can be reached due to the small sample size. Our results indicate that pretreatment semen quality in these patients is adequate for reproductive techniques. We believe that cryopreservation should be offered to patients of reproductive age with disease or treatment regimens that may cause infertility. PMID- 11780926 TI - Pilot study of the endothelin-A receptor selective antagonist BMS-193884 for the treatment of erectile dysfunction. AB - Endothelins have been postulated to be important regulators of penile erectile function. The endothelin-A receptor antagonist BMS-193884 was evaluated as a treatment for mild-to-moderate erectile dysfunction in an animal model and in human volunteer subjects. In laboratory studies, organ bath preparations of rabbit and human penile cavernosal tissue strips were incubated with BMS-193884 and exposed to increasing concentrations of endothelins. In rabbit tissue, 1 microM BMS-193884 significantly inhibited contraction to ET-1, ET-2, and ET-3 by 34.5%, 42.9%, and 100%, respectively. In human tissue, 1 microM BMS-193884 inhibited contraction to ET-2 by 44.4%. In rabbit tissue strips contracted with 20 nM of ET-1 or ET-2, BMS-1 93884 caused dose-dependent relaxation with EC50 values of 107.2 +/- 32.3 nM and 1.7 +/- 0.5 nM, respectively. In anesthetized male rabbits, intravenous administration of BMS-193884 (systemic plasma concentration approximately 50 and 100 nM) increased the duration of pelvic nerve stimulated penile erection. To further assess the safety and efficacy of BMS 193884, 53 men diagnosed with mild-to-moderate erectile dysfunction were administered oral placebo or 100 mg BMS-193884 in a double-blind fashion. Evaluations were based on 1) erectile function testing during 2 in-office visits and 2) diary and questionnaire data of 4 intercourse attempts over 2-4 weeks of home use. Although the drug was well tolerated, BMS-193884 did not significantly improve erectile function during office visits or home use when compared to placebo. Thus, BMS-193884 facilitated cavernosal smooth muscle relaxation ex vivo and prolonged penile tumescence in vivo. In contrast, a pilot clinical study failed to show enhancement of erectile response in men with mild-to-moderate erectile dysfunction. The disparity between the laboratory and clinical studies suggests that there may be differences between species with regard to the role of endothelin in erectile function. PMID- 11780928 TI - Vitamin D and prostate cancer. AB - The original hypothesis of Schwartz and Hulka (1990) proposing that vitamin D deficiency may be a risk factor for prostate cancer has triggered many studies. Epidemiological studies have supported this hypothesis with findings that sunlight exposure is inversely proportional to prostate cancer mortality and that prostate cancer risk is greater in men with lower levels of vitamin D (Hanchette and Schwartz, 1992; Corder et al, 1993; Ahonen et al, 2000). Prostate cancer cells express receptors for 1,25(OH)2D3 and some cell lines are growth inhibited when treated with 1,25(OH)2D3 (reviewed in Blutt and Weigel, 1999). The mechanism of action of these growth inhibitory effects of 1,25(OH)2D3 in LNCaP cells involves G1 accumulation, induction of quiescence, and an increase in apoptosis of the cancer cells (Blutt et al, 1997, 2000a; Zhuang and Burnstein, 1998). In vivo, 1,25(OH)2D3 and its analogs slow tumor growth and hinder metastasis of prostate tumors in rodent models (Schwartz et al, 1995; Getzenberg et al, 1997; Lokeshwar et al, 1999; Blutt et al, 2000b), and 1,25(OH)2D3 may have clinically relevant effects (Gross et al, 1998). More work is required to elucidate the mechanism of 1,25(OH)2D3 action in prostate cancer cells and to identify optimal 1,25(OH)2D3 analogs in a search for compounds with a better separation of growth inhibitory effects from hypercalcemic effects. PMID- 11780927 TI - Testosterone release from a subcutaneous, biodegradable microcapsule formulation (Viatrel) in hypogonadal men. AB - Men with hypogonadism require testosterone replacement for optimal health. In the United States, testosterone is currently administered by daily transdermal patches, topical gels or intramuscular injections every 1-3 weeks. Biodegradable polylactide-co-glycolide microcapsules are currently used for long-term drug delivery in humans. Such microcapsules that contain testosterone could provide a better means of long-term testosterone therapy. We therefore studied the pharmacokinetics and pharmacodynamics of testosterone release from testosterone microcapsules in men with hypogonadism. Fourteen men who had been treated previously with testosterone were enrolled in an open-label, prospective study of testosterone microcapsule administration. Subjects were enrolled if 2 consecutive serum total testosterone levels were lower than 8.7 nmol/L after a 4-week washout from testosterone therapy. Subjects were injected with a single dose of either 267 mg (n = 7) or 534 mg (n = 7) of (Viatrel) testosterone microcapsule, and serum total testosterone, dihydrotestosterone, estradiol, sex-hormone binding globulin, luteinizing hormone, and follicle-stimulating hormone levels were determined at days -14, -7, and 0 before the injection; at days 1, 2, and 7 after the injection; and then weekly thereafter for 8-12 weeks. Mean serum total testosterone levels peaked immediately following injection on day 1 at 25.2 +/- 2.6 nmol/L in the 267 mg group and 34.7 +/- 2.4 nmol/L in the 534 mg group. Total serum testosterone levels declined gradually and fell below 8.7 nmol/L at 42 days after injection in the 267 mg group, and 70 days after injection in the 534 mg group. Estradiol and dihydrotestosterone levels followed a similar pattern. Mean serum free testosterone also peaked immediately following injection on day 1 at 0.51 +/- 0.05 nmol/L in the 267 mg group and 0.97 +/- 0.08 nmol/L in the 534 mg group. No significant adverse reactions were seen, although 2 subjects complained of transient tenderness and fullness at their injection sites. We conclude that a single injection of 534 mg of testosterone microcapsules to men with hypogonadism normalizes serum hormone levels for up to 10-11 weeks, albeit with a pronounced early peak and a relatively long period of low-normal serum total testosterone. Subcutaneously administered testosterone microcapsules may provide a safe and convenient method for the long-term treatment of male hypogonadism or testosterone replacement in male contraceptive regimens. PMID- 11780929 TI - Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase. AB - With the current understanding that nitric oxide (NO) mediates penile erection, the endothelial isoform of NO synthase (eNOS) has been implicated in this function. We undertook this study applying transgenic mice with targeted deletion of the eNOS gene (eNOS-/- mice) as an experimental approach to evaluate the importance of eNOS in cholinergically stimulated erectile function in vivo. Combined pharmacostimulation with intracavernosal carbachol (3 ng) administration and submaximal cavernous nerve (CN) electrical stimulation (16 Hz, 5 millisecond, 1 V) simultaneous with intracavernosal pressure (ICP) monitoring, and both biochemical assay of NO synthase activity and Western blot analysis of eNOS protein content in penile tissue, were performed on eNOS-/- mice and wild-type controls. Combined intracavernosal carbachol administration and submaximal CN electrical stimulation raised the recorded ICP, elicited by CN electrical stimulation alone in wild-type mice (from 35.7 +/- 2.7 to 48.1 +/- 5.5 mm Hg, P < .05) but not in eNOS-/ - mice (from 54.9 +/- 6.3 to 51.0 +/- 9.5 mm Hg, not significant [NS]). Pretreatment with the nonselective nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 100 mg intracavernosally) blocked electrically stimulated ICP responses in eNOS-/- mice to baseline levels (37.8 +/- 4.4 vs 12.7 +/- 4.0 mm Hg, P < .05). In penes of eNOS-/- mice, approximately 60% NO synthase activity of wild-type penis levels was retained (NS), and eNOS protein was absent. We concluded that eNOS-/- mice preserve erectile function on the basis of a noncholinergic but NO-dependent mechanism and that eNOS physiologically mediates penile erection under cholinergic stimulation. PMID- 11780931 TI - The effects of assisted reproduction on the trends and zygosity of multiple births in England and Wales 1974-99. AB - Assisted reproductive techniques have led to an increase in the proportion of maternities that are multiple. Though predominantly dizygotic, they are at greater risk of monozygotic division than those spontaneously conceived. England and Wales data 1974-99 on stillbirths and livebirths were analysed for 4 periods: 1974-80 (pre-assisted reproduction; 1982-8; 1989-91 (pre-redefinition of stillbirth); 1993-9 (post-redefinition of stillbirth). For twin data, Weinberg's rule was applied to estimate the proportions that were mono- (MZ) and dizygotic (DZ). Compared with the period before assisted reproduction, the most recent period shows an increase in twin maternities of 3.81 per 1,000 comprised of 3.22 (95% CI 3.10 to 3.33; p < 0.0001) DZ and 0.60 (95% CI 0.51 to 0.68; p < 0.0001) MZ twins. It is estimated that 15.7% of assisted reproduction twins are MZ. Higher order multiple births showed an increase of 3.06 (95% CI 2.85 to 3.29; p < 0.0001) per 10,000 maternities. Stillbirth rates in MZ twins are of the same order of magnitude as those in higher order multiple births but higher than those in DZ twins. The improvement in stillbirth rates over the 26 year study period is of the same order magnitude in singletons, DZ and MZ twins and higher order multiples. Assisted reproduction has led to a significant increase in the proportion of MZ twins. These are at high risk of fetal death and this needs to be considered when local stillbirth and perinatal mortality rates are used in auditing obstetric services. PMID- 11780930 TI - Induction of the acrosome reaction and zona-free hamster oocyte penetration by a bull with complete teratospermia versus a half brother with normal sperm. AB - A fertile bull producing normal sperm and a sterile half brother exhibiting 100% teratospermia were available to study an induced sperm acrosome reaction and oocyte penetration. Pedigree analysis indicated that this condition was inherited. Experiments were undertaken to study the induction of the acrosome reaction using dilaurylphosphatidylcholine (PC12) liposomes, because this procedure was previously established to be highly correlated with bull fertility. The sperm from each bull were incubated with several PC12 concentrations for varying time periods. The initial percentages of sperm from the sterile bull with intact, partially intact, and lost acrosomes were 67%, 18%, and 14%, respectively, vs 82%, 13%, and 5% for the fertile bull (P < .05). After incubation for 15 minutes with 50 microM PC12 liposomes the corresponding values were, respectively, 51%, 26%, and 19%; and 60%, 28%, and 12%. Thus, the differences after induction of the acrosome reaction, although significant (P < .05), were small. The number of sperm adhered to each oocyte averaged 22 and 10, respectively, for the fertile and sterile bulls, whereas 74% of the fertile bull sperm and only 11% of the sterile bull sperm penetrated oocytes. Mixing the sperm oocyte complex during incubation and increasing the sperm concentration during incubation to compensate for differences in sperm motility did not markedly affect oocyte penetration by teratogenic sperm, which is consistent with this bull being sterile. In other studies, microinjection of this type of sperm was demonstrated to induce fertilization, so the consequences of using sperm with hereditary defects in assisted reproductive programs to overcome human male sterility may be a concern. PMID- 11780932 TI - Multi-fetal pregnancy reduction does not influence perinatal results in twin pregnancies. AB - The objective of this study was to compare perinatal results in multifetal pregnancies where the reduction to twins was performed with non-reduced twin pregnancies. Perinatal results in 99 sets of twins after transabdominal multifetal pregnancy reduction of triple and higher-order multiple pregnancies performed in a single center were compared with a control group consisting of 151 twin pregnancies conceived in the same time period after infertility treatment, which were not a result of reduction. The main outcome measures were length of pregnancies, weight of the newborns, percentage of miscarriages and the mode of the delivery were analyzed. No significant difference could be found at a 5% level of significance regarding the average duration of pregnancy or average weight of the twins. Fisher test on 5% significance level did not ascertain any significant difference in the probability of miscarriage between the group with reduction (5.26%) and the group without reduction (12.84%). At a 5% level of statistical significance, no significant difference in probability of perinatal death of the fetus or delivery of a stillborn fetus was found. The percentage of cesarean sections did not differ significantly in both groups. The analysis of both groups demonstrated that reduction of multifetal pregnancies to twins may not influence perinatal results in comparison to twin pregnancies where reduction was not performed. PMID- 11780933 TI - The rate of preterm twin births (22-27 weeks) as a criterion for measuring the quality of prenatal care. AB - While the true figures are not well established, outcomes of twin pregnancies are directly dependent on a small number of preterm births between 22 and 27 weeks. Observation of perinatal outcomes in twin pregnancies yields two contradictory results. Firstly, it shows an improvement in perinatal mortality figures. Secondly, it reveals an increase in the rates of preterm deliveries. These findings result from the observation of 783 twin pregnancies followed and delivered in a level 3 perinatal centre in Paris between 1993 and 1998. Women followed since the beginning of pregnancy through the outpatient clinic of the institution are included in this number, as are women who were referred or transferred to the centre at a later date due to complications, This analysis reflects the influence of two contrasting policies. The first, and less recent policy is devoted to the prevention of preterm births, and is reflected by the low number of extremely preterm deliveries at 22-32 weeks. The second is the effect of our new approach to the prevention of foetal deaths in relation to foetal growth retardation in twins which has resulted in increased medical intervention such as the induction of labour or scheduled Caesarean birth. This has resulted in an increase in twin preterm births from 33 to 36 weeks, with the expected result of fewer foetal deaths. PMID- 11780934 TI - Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience. AB - With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants. PMID- 11780935 TI - Genetic and environmental influences on self-esteem in a Japanese twin sample. AB - The purpose of the present study is to clarify the mechanism of Japanese self esteem (SE) in genetic and environmental influences using twin methodology. Eighty-one pairs of adolescent twins, including 50 pairs of monozygotic (MZ) twins and 31 pairs of dizygotic (DZ) twins, participated in this study. Self esteem was assessed using the Rosenberg Self-Esteem Scale (RSES), translated into Japanese. As a result of using univariate twin analyses, model comparisons using the Akaike Information Criterion (AIC) indicated that the AE model was the best fit (AIC = -5.35). In the best-fitting AE model, the heritability (a2) of SE was revealed to be moderate, accounting for 49% of the variance; environmental influences (individual-specific environmental factors) explained 51% of the variance. These results are consistent with the findings of some behavioral genetics studies of SE in the West and show that there is no difference between Western and Japanese populations in the mechanism of SE considering genetic and environmental influences. The results also suggest the importance of considering both genetic and environmental factors in studies of Japanese SE. PMID- 11780936 TI - Examining the dimensions of intimacy in twin and peer relationships. AB - While it is widely assumed that twinsh p involves high levels of intimacy to the detriment of other relationships, an examination of twinship using measures of intimacy has not yet been conducted. Participants were 214 individua twins (128 MZ, 62 DZ same-sex, and 24 DZ mixed-sex) between 16-73 years of age. Twins completed measures of intimacy in reference to their co-twin, their closest same sex friend, and their closest other-sex friend. As expected, the highest level of intimacy was reported for the co-twin. Contrary to expectation, MZ twins did not report significantly higher levels of intimacy with their co-twin, or significantly lower levels of intimacy with their closest friends when compared to DZ same-sex or DZ mixed-sex twins. Furthermore, twins who reported high levels of intimacy with their co-twin did not report significantly lower levels of intimacy with their closest friends. Implications and directions for future research are discussed. PMID- 11780937 TI - Genetic and environmental influences on the associations between attention problems and other problem behaviors. AB - Problem behavior in children shows a high degree of co-occurrence, both within the domains of internalizing and externalizing behaviors and across domains. Maternal ratings of 207 same- and opposite-sex twin pairs on the Child Behavior Checklist (CBCL/4-18; Achenbach, 1991) were used to determine the etiology of these associations. In the current sample of 4- to 11-year-old children (mean age: 7.6 years) phenotypic correlations were .68 between Internalizing and Externalizing, between .41 and .66 within the internalizing scales, and between .58 and .71 within the externalizing scales. Correlations across domains on the scale level were of similar magnitude. Genetic and shared environmental correlations were generally high, with the exception of the somatic complaints scale which showed low genetic correlations with other scales. These findings of uniformly high shared etiology was seen within and across domains. For example, Attention Problems showed genetic correlations of .65 with Delinquent Behavior and .76 with Aggressive Behavior; the genetic correlations of Attention Problems with internalizing scales were .71 for Anxious/Depressed and .79 for Withdrawn; a low genetic correlation was only shown for the Somatic Complaints scale (r(g) = .16). Although the magnitude of shared environmental contributions was lower, the environmental correlations were close to unity, indicating that the same family environmental factors were involved in aspects of problem behavior when assessed across domains. Results for the Attention Problems scale were similar to other disruptive behavior, justifying its inclusion with the externalizing scales. PMID- 11780938 TI - Feasibility of using different approaches for recruiting younger twins to establish a population based twin register in Sri Lanka. AB - Identifying twins for a population-based register can be achieved through birth records or community surveys. We studied the feasibility and effectiveness of different methods of identifying and recruiting twins to establish a population based register. To trace twins a population survey was carried out using an interviewer administered questionnaire. We also inspected the birth registration certificates at a divisional secretariat reported from a specified hospital between the years of 1985-1997 and compared it to the birth register of this same hospital. To recruit twins a random sample of 75 twin pairs (150 twins) identified at the Divisional Secretariat were contacted through the post and 25 twin pairs (50 twins) were personally visited. The prevalence of twins was 6.5 twins per 1000 people in the area surveyed. The twinning rate at the hospital was 18.92 twins per 1000 births. A discrepancy of 38 multiples births between the hospital labour room records and those registered at the DS was noted. The response from the postal invitation for recruitment was 59% and the response from the personal invitation was 68%. (Difference 9.4% 95% CI; 7.06-11.73). Community survey and systematic inspection of birth records either at the hospital or the birth registration office was an effective method to trace twins. Once traced, personal contact was more effective than the postal invitation for recruitment of younger twins. A cost-effective approach would be to use a postal coverage followed by personal contact for non-responders. The alternative method, community coverage, would have financial implications. PMID- 11780939 TI - Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. AB - The classic twin study is sometimes described as "the perfect natural experiment" for the investigation of the aetiology of complex disease, but assumptions of the twin design need to be empirically tested if their results are to be considered unbiased and representative of singleton populations. In this study comparisons of disease and prevalence of lifestyle characteristics have been made between twin participants in the St Thomas' Hospital UK adult twin registry, the largest twin volunteer register in the UK for the study of diseases of ageing, and a parallel population-based study of singleton women. The only differences found were for weight, where monozygotic (MZ) twins were lighter and had a smaller variance than dizygotic (DZ) twins and singletons. For the other variables studied, volunteer twins were not found to differ from age-matched singleton women in distribution or prevalence of: bone mineral density, osteoarthritis, blood pressure, hypertensive drug use, height, history of hysterectomy and ovariectomy, menopausal status and current alcohol and overall tobacco consumption. We conclude that the results of twin studies can be generalised to singleton populations for these measures and disease outcomes. PMID- 11780940 TI - Twin studies of dietary behaviors: why we eat when we do. PMID- 11780941 TI - Redux: the James Shields Memorial Award for Twin Research. PMID- 11780942 TI - Postsurgical changes in self-reported mood and Composite IQ in a matched sample of patients with frontal and temporal lobe epilepsy. AB - Changes in self-reported mood assessed by the Beck Depression Inventory (BDI) were examined in a sample of 60 left-hemisphere speech-dominant patients who underwent epilepsy surgery (15 right frontal, 15 left frontal, 15 right temporal, 15 left temporal). Temporal lobectomy patients were matched to frontal lobectomy patients by presurgical BDI scores, premorbid K-BIT composite IQ, sex, age, and years since seizure onset. Overall, self-reported mood improved following surgery, with men showing a greater improvement than women. There were no differences among the four groups in terms of pre-surgical and post-surgical reported mood. However, frontal patients showed more extreme changes in mood in either direction than temporal patients. Additionally, while temporal patients showed gains in Composite IQ, no such gains were observed in frontal patients. Changes in mood in frontal patients were not related to postsurgical seizure outcome or time since surgery, but were related to changes in Composite IQ. PMID- 11780943 TI - Neuropsychological effects of prefrontal slow rTMS in normal volunteers: a double blind sham-controlled study. AB - Recent reports have suggested that repetitive transcranial magnetic stimulation (rTMS) is effective in major depression. Unlike ECT, rTMS does not involve a seizure and is associated with minimal side-effects, including cognitive difficulties. However, the effect of rTMS on cognitive functioning has not been systematically evaluated. This study was designed to examine the neuropsychological effects of slow rTMS in normal volunteers. Forty-six normal volunteers were randomly assigned to receive one session of right (N = 16) or left prefrontal (N = 15), or sham (N = 15) rTMS at 1 HZ. Patients were assessed before and after stimulation by a computerized neurospychological battery. All three groups showed significant improvement over time in processing speed (reaction time) and efficiency (correct responses per unit of time). However, no time by group interaction was found for any of the neuropsychological tests. These findings suggest that a single session of slow rTMS does not interfere with neurospychological functioning in normal volunteers, supporting clinical reports of no adverse cognitive effects. PMID- 11780944 TI - Inhibition of return in aging and Alzheimer's disease: performance as a function of task demands and stimulus timing. AB - Inhibition of return (IOR) is a phenomenon of spatial attention that biases attention toward novel events in the environment. Recent evidence suggests that the magnitude and timing of IOR varies as a function of task conditions (e.g., detection vs. discrimination tasks, short vs. long cue-target intervals, intrinsic vs. extrinsic cues). Although IOR appears relatively preserved with both normal aging and Alzheimer's disease (AD), it has been tested under relatively simple task conditions. To test whether IOR is resistant to age and / or AD when cognitive demands are increased, we employed a double-cue IOR paradigm that required categorization as well as detection responses. The stimulus onset asynchrony (SOA) between the cue and target events was varied to determine whether group differences existed in IOR effects over time. Younger normal adults and older normal adults exhibited significant IOR effects on both the detection task and the categorization task at a short cue-target SOA (950 ms). In contrast, AD patients exhibited significant IOR effects at the short SOA on the detection task but not on the categorization task. From the short to the long SOA (3500 ms), IOR effects exhibited by younger normal adults declined significantly during both the detection and the categorization tasks, suggesting that inhibition resolved over time. In contrast, neither older normal adults nor AD patients exhibited SOA-related IOR reductions on the detection task. These results suggest that IOR may show differential age- and AD-related vulnerabilities depending on task conditions and timing characteristics. PMID- 11780945 TI - The neurocognitive phenotype of the 22q11.2 deletion syndrome: selective deficit in visual-spatial memory. AB - The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is associated with a high frequency of learning disabilities. Although previous work has demonstrated that verbal skills are typically better preserved than non-verbal skills on both IQ and academic achievement testing in children with this syndrome, such measures are not sufficiently specific to determine a selective cognitive deficit. As part of an ongoing prospective study of patients with this syndrome, 29 children aged 5-17 with confirmed 22q11.2 deletions were assessed with a comprehensive neuropsychological test battery, including matched tasks of verbal and visuospatial memory. Results indicate that 22q patients displayed a selective deficit in visual-spatial memory, which was mirrored by deficits in arithmetic and general visual-spatial cognition. Further, a dissociation between visual-spatial and object memory was observed, indicating further selectivity of this pattern of deficit, and providing evidence for the dissociability of these components of visual cognition. These results indicate that children with 22q11.2 deletions display a specific neurocognitive phenotype, and suggest that this region of Chromosome 22q11 may harbor a gene or genes relevant to the etiology of nonverbal learning deficits. PMID- 11780946 TI - Influence of centrality and distinctiveness of actions on script sorting and ordering in patients with frontal lobe lesions. AB - In order to further investigate script knowledge in patients with frontal lobe lesions (FP), 30 participants with frontal brain damage, 14 controls with posterior brain damage (PC) and 30 normal controls (NC) were asked to sort script actions with various degrees of centrality and distinctiveness according to the script to which they belonged and their order of execution. Actions were given in 3 conditions: scripts with headers (SH), scripts without headers (SwH) and scripts with distractor header (SDH). Results confirmed the dual dissociation we observed in a previous study (Allain, Le Gall, Etcharry-Bouyx, Aubin, & Emile, 1999). Twelve FP made numerous errors in sequencing actions regardless of the conditions, but rejected the irrelevant title. Fourteen FP made few sequencing errors but used the irrelevant title. The last 4 FP performed as well as the PC and NC in every condition. Sorting errors made by the FP mainly concerned actions with low levels of centrality and distinctiveness. These data are consistent with the view that frontal lobe lesions selectively impair the syntactic component of script representation without affecting its semantic component. PMID- 11780947 TI - Associations to smell are more pleasant than to sound. AB - To assess and compare the quantitive and qualitative aspects of verbal associations of olfaction and audition, we conducted two verbal category fluency tasks, one consisting of the generation of 'smelling' associations and the other of 'auditory' associations. The responses of the 40 subjects on these fluency tasks were rated as pleasant or unpleasant by themselves as well as by an independent group of 40 subjects. In addition, all 80 healthy, right-handed subjects rated their momentary emotional state on a visual analog scale. The mean number of words generated by the 40 subjects did not differ between the two tasks, and in both tasks pleasant associations were more frequent than unpleasant associations. However, for all subjects, the proportion of pleasant associations was significantly higher in the olfactory compared to the auditory fluency task. The finding of more pleasant associations in both tasks confirms previous reports, but the pronounced effect in the olfactory task suggests that odors may be more hedonically coded than other sensory modalities, i.e., audition. Although there is evidence that the majority of odors are initially perceived as unpleasant, when retrieved from memory, pleasant connotations seem to dominate. The possible mechanisms for this dissociation are discussed. PMID- 11780948 TI - Are some memory deficits unique to lesions of the mammillary bodies? AB - The role of the mammillary bodies in human memory is still in debate. A recent model of human amnesia proposes similar functions for the mammillary bodies and the hippocampus. But the main evidence for this model comes from animal studies using the delayed non-matching to sample paradigm. We describe a patient who developed a severe memory impairment after surgical removal of a germinoma. Postsurgical high resolution MRI revealed bilaterally shrunken mammillary bodies and an infarct of the left mammillary body. There were no other relevant lesions. Neuropsychological testing showed mildly impaired frontal lobe functions (executive functions, working memory and word fluency), almost intact learning and recognition, but severely impaired free and delayed recall. Experimental investigations revealed a reduced but preserved release of proactive interference and a pronounced impairment of recency and source judgments. We conclude that the mammillary bodies do play a prominent role in human memory, although the role differs slightly from that of the hippocampus. PMID- 11780949 TI - Semantic priming in Parkinson's disease: evidence for delayed spreading activation. AB - Nineteen persons with Parkinson's disease (PD) and 19 matched control participants completed a battery of online lexical decision tasks designed to isolate the automatic and attentional aspects of semantic activation within the semantic priming paradigm. Results highlighted key processing abnormalities in PD. Specifically, persons with PD exhibited a delayed time course of semantic activation. In addition, results suggest that experimental participants were unable to implicitly process prime information and, therefore, failed to engage strategic processing mechanisms in response to manipulations of the relatedness proportion. Results are discussed in terms of the 'Gain/Decay' hypothesis (Milberg, McGlinchey-Berroth, Duncan, & Higgins, 1999) and the dopaminergic modulation of signal to noise ratios in semantic networks. PMID- 11780950 TI - Haptic perception in anorexia nervosa before and after weight gain. AB - Haptic perception of patients with anorexia nervosa (n = 10) was analyzed in a longitudinal study (T0-T1). The haptic explorations consisted of palpating the structure of 12 sunken reliefs in sequence with both hands, eyes closed. After each exploration the structure was reproduced on a piece of paper. In the anorexia group, mean exploration time was significantly shorter than in healthy control subjects. However, the reproductions of complex stimuli submitted by the anorexia group were of notably poorer quality than those of the healthy controls. This was also observed after weight gain (T1). The results of the haptic explorations can be interpreted as a cortical dysfunction and deficits in somatosensorical integration processing in patients with anorexia nervosa. This may be due to a disorder of tactual-spatial processing in the right parieto occipital regions. PMID- 11780951 TI - Meaning of reliability in terms of correct and incorrect clinical decisions: the art of decision making is still alive. AB - Examples using cut-off scores are presented to show the effects of measurement error (unreliability) on making correct and incorrect clinical decisions. These decisions are presented in terms of true positives (TPs), true negatives (TNs), false positives (FPs), and false negatives (FNs). A discussion of the difficulty in establishing reliability standards is presented. PMID- 11780952 TI - Discourse priming of homophones in individuals with dominant nonthalamic subcortical lesions, cortical lesions and Parkinson's disease. AB - An on-line priming experiment was used to investigate discourse-level processing in four matched groups of subjects: individuals with nonthalamic subcortical lesions (NSL) (n = 10), normal control subjects (n = 10), subjects with Parkinson's disease (PD) (n = 10), and subjects with cortical lesions (n = 10). Subjects listened to paragraphs that ended in lexical ambiguities, and then made speeded lexical decisions on visual letter strings that were: nonwords, matched control words, contextually appropriate associates of the lexical ambiguity, contextually inappropriate associates of the ambiguity, and inferences (representing information which could be drawn from the paragraphs but was not explicitly stated). Targets were presented at an interstimulus interval (ISI) of 0 or 1000 ms. NSL and PD subjects demonstrated priming for appropriate and inappropriate associates at the short ISI, similar to control subjects and cortical lesion subjects, but were unable to demonstrate selective priming of the appropriate associate and inference words at the long ISI. These results imply intact automatic lexical processing and a breakdown in discourse-based meaning selection and inference development via attentional/strategic mechanisms. PMID- 11780953 TI - The influence of task characteristics on the intermanual asymmetry of motor overflow. AB - The two studies reported here were designed to test the proposition that greater motor overflow occurs when movements are performed by the non-dominant hand. Unlike previous studies using normal adults, the task in these studies did not require force production. In the first study, a group of 19 right-handed participants performed unweighted finger lifting. That the frequency of motor overflow occurrence was the same regardless of which hand performed the task, did not support findings from other studies where tasks involving force production resulted in more overflow when performed by the non-dominant hand. To investigate further the influence of task characteristics on motor overflow occurrence, in the second study participants were required to remember and reproduce a prescribed sequence of four finger lifts. Left- and right-handed participants (N = 30) performed both single and sequenced finger lifting. The relative frequency of motor overflow (unintended lifts of fingers of the passive hand) was compared between hand preference groups, active hand and task type (single/sequenced). Contrary to the expectation that motor overflow would be greater for the sequenced finger lifting task, overflow was exhibited with a significantly greater frequency on single finger lifting. This finding indicates that task characteristics influence the pattern of overflow occurrence in normal adults. The task used in this study did not involve force production and did not result in an intermanual asymmetry of motor overflow. This contrasts with findings from other studies requiring adults to exert forces where greater overflow occurred when the non-dominant hand was active. However, this study confirms previous findings which show that left-handers produce greater overflow compared to right handers regardless of the task being performed and the hand performing the task. PMID- 11780954 TI - Enalapril: pharmacokinetic/dynamic inferences for comparative developmental toxicity. A review. AB - Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the second and third trimester of pregnancy in humans is associated with specific fetal and neonatal injury. The syndrome, termed "ACEI fetopathy" in humans, does not appear to have a similar counterpart in experimental animals. The present paper reviews pharmacokinetic and pharmacodynamic aspects of enalapril that are physiologically important during pregnancy and intrauterine development in humans and in experimental animal species with the aim of better understanding the comparability of the manifestations of enalapril developmental toxicity in animals and humans. The human fetus is at a disadvantage with regard to in utero enalapril exposure in comparison to some of the animal species for which gestational pharmacokinetic data are available. Important reasons for the higher vulnerability of the human fetus are its accessibility by enalapril and the earlier (relative to animal species) intrauterine development of organ systems that are specific targets of ACEI pharmacologic effect (the kidney and the renin-angiotensin system). In humans, these systems develop prior to calcarial ossification at the end of first trimester of pregnancy. The specific pharmacodynamic action of enalapril on these systems during fetal life is the chief determinant of the etiology and pathogenesis of ACEI fetopathy in humans. In contrast, in most of the studied animal species, these target systems are not developed until close to term when the fetus is relatively more mature (and therefore less vulnerable), so that the window of vulnerability is narrower in comparison to the human. Among animal species, the best concordance in fetal pharmacodynamics to the human is seen in the rhesus monkey, but further studies are necessary to determine if similar developmental pathology is induced in this animal model upon repeated administration of the drug during the relevant period of intrauterine development. Animal-human concordance of developmental toxicity is least likely in the rat because of greater disparities in enalapril availability to the fetus and the relative development of the kidney and skeletal ossification compared to that in humans. PMID- 11780956 TI - Developmental toxicity evaluation of unleaded gasoline vapor in the rat. AB - To evaluate the potential of unleaded gasoline vapor for developmental toxicity, a sample was prepared by slowly heating API 94-02 (1990 industry average gasoline) and condensing the vapor. The composition of this vapor condensate, which comprises 10.4% by volume of the starting gasoline, is representative of real-world exposure to gasoline vapor encountered at service stations and other occupational settings and consists primarily of volatile short chain (C4-C6) aliphatic hydrocarbons (i.e. paraffins) with small amounts of cycloparaffins and aromatic hydrocarbons. A preliminary study in rats and mice resulted in no developmental toxicity in either species. However, a slight reduction in maternal body weight gain in rats led to the selection of rats for this guideline study. Groups of pregnant rats (n = 24/group) were exposed to unleaded gasoline vapor at concentrations of 0, 1000, 3000, or 9000 (75% lower explosive limit) ppm equivalent to 0, 2653, 7960, or 23,900 mg/m3, for 6 h/day on gestation days 6-19. All rats were sacrificed on gestation day 20. No maternal toxicity was observed. Developmentally, there were no differences between treated and control groups in malformations, total variations, resorptions, fetal body weight, or viability. The maternal and developmental NOAEL is 9000 ppm. Under conditions of this study, unleaded gasoline vapors did not produce evidence of developmental toxicity. PMID- 11780955 TI - Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects sperm from DNA damage and apoptosis caused by benzo(a)pyrene. AB - Benzo(a)pyrene (BaP), an aryl hydrocarbon receptor (AhR) ligand present in cigarette smoke and car exhaust, is thought to have negative effects on male reproduction. We hypothesized that BaP damages sperm through AhR activation, phase I enzyme induction, DNA adduct formation, and increased germ cell apoptosis in the testis, and that resveratrol, a natural competitive inhibitor of the AhR found in some red wines, could prevent the adverse effects of BaP on sperm. Male Balb C mice were injected subcutaneously (s.c.) for 5 weeks with a range of BaP doses (0.5 mg/kg to 50 mg/kg). Live sperm were obtained from the vas deferens, counted, and stained to measure annexin-V positive (apoptotic) cells. In a subsequent study, mice were injected for 5 weeks with corn oil (control), BaP (5 mg/kg/week), or BaP plus resveratrol (50 mg/kg/week) (n = 3 per group). Immunohistochemistry (IHC) was performed on testis sections for the determination of CYP1A1, BaP diol epoxide (BPDE) DNA adducts, and apoptosis and the results quantified by using the HSCORE, a semiquantitative scoring system. Our results demonstrated that sperm counts after 5 weeks were inversely correlated to BaP dosage. BaP (0.5 to 5 mg/week) positively correlated with sperm apoptosis while higher doses increased sperm necrosis. CYP1A1 protein was observed mainly in interstitial cells of some testis sections, but there was no significant induction by BaP. BPDE DNA adducts were induced in all components of the seminiferous tubules by BaP and suppressed by resveratrol: median HSCORE (interquartile range) control 61 (52-71.5); BaP 213 (192-248), P = 0.01 compared to control; BaP plus resveratrol 83 (70-90). BaP significantly increased apoptosis, mainly in spermatogonia: medain HSCORE (interquartile range) BaP 189 (161-223) versus control 83 (57-93), P < 0.01; and this effect was abrogated by resveratrol. Median HSCORE for BaP plus resveratrol was 112 (range 99-121). In summary, BaP caused increased sperm cell BPDE DNA adduct formation and apoptosis in the mouse. The natural AhR antagonist, resveratrol diminished BaP-induced DNA adducts and apoptosis in seminiferous tubules. PMID- 11780957 TI - Gonadotropin regulation of glutathione synthesis in the rat ovary. AB - Glutathione (GSH), an antioxidant and conjugator of electrophilic toxicants, prevents toxicant-mediated destruction of ovarian follicles and oocytes. Ovarian GSH has previously been shown to change with estrous cycle stage in rats, suggesting that the gonadotropin hormones may regulate ovarian GSH synthesis. The present studies tested the hypotheses that [1] estrous cycle-related changes in ovarian GSH result from cyclic changes in protein and mRNA expression of the rate limiting enzyme in GSH synthesis, glutamate cysteine ligase (GCL, also called gamma-glutamylcysteine synthetase), and [2] that these changes result from gonadotropin-mediated regulation of GCL subunit expression. In the first experiment, ovaries were harvested from cycling adult female rats on each stage of the estrous cycle. In the second experiment immature female rats were injected with pregnant mare's serum gonadotropin (PMSG) to stimulate follicular development or with vehicle and killed 8, 24, or 48 h later. In both experiments the ovaries were harvested for [1] total GSH assay, [2] Western analysis for GCL catalytic (GCLc) and regulatory (GCLm) subunit protein levels, or [3] Northern analysis for Gclc and Gclm mRNA levels. Ovarian GSH concentrations and Gclc and Gclm mRNA levels, but not GCL subunit protein levels, varied significantly with estrous cycle stage. PMSG administration significantly increased ovarian GSH concentrations 24 and 48 h later. GCLm protein levels increased significantly at 24 h and 48 h following PMSG. GCLc protein levels did not increase significantly following PMSG. Gcl subunit mRNA levels were not significantly increased at any time point by the planned ANOVA; however, an increase in Gelc at 48 h was identified by t-testing. These results support the hypothesis that gonadotropins regulate ovarian GSH synthesis by modulating GCL subunit expression. PMID- 11780958 TI - Rat two-generation reproductive toxicity study of bisphenol A. AB - This study was conducted to determine the low-dose effects of bisphenol A (BPA) in a rat two-generation reproduction study. Groups of 25 male and 25 female Crj: CD (SD) IGS rats were given BPA at 0.2, 2, 20, or 200 microg/kg/day by gastric intubation throughout the study beginning at the onset of a 10- and 2-week premating period, in F0 males and females, respectively, and continuing through the mating, gestation, and lactation periods, for two generations. There were adult (F0, F1, F2) and postnatal day (PND) 22 (F1, F2) necropsies: the oldest F2 males and females being killed at postnatal weeks 7 and 14, respectively. No compound-related clinical signs or effects on body weight or food consumption were observed in any generation. There were no compound-related changes in surface righting reflex, negative geotaxis reflex, mid-air righting reflex, pinna detachment, incisor eruption, eye opening, testes descent, preputial separation, or vaginal opening in F1 and F2 generations, or behavior in the open field or water filled multiple T-maze in the F1 generation. No test compound-related changes in estrous cyclicity, copulation index, fertility index, number of implantations, gestation length, litter size, pup weight, pup sex ratio, pup viability, or other functional reproductive measures were noted in any generation. A few significant changes in the anogenital distance (AGD) per cube root of body weight ratio were found at 0.2 and 20 microg/kg in F1 males, at 2, 20, and 200 microg/kg in F1 females, and at 20 and 200 microg/kg in F2 females. However, the changes in the AGD were consistently small (within 5% of control values), and no continuous changes in the AGD or AGD/cube root of body weight ratio were detected. There were no compound-related changes in epididymal sperm counts or motility in F0 and F1 males. No compound-related necropsy findings or effects on organ weight including the reproductive organs were found in any generation. Histopathologic examinations revealed no evidence of compound-related changes in any organs including the reproductive organs of both sexes. The data indicate that oral doses of BPA of between 0.2 and 200 microg/kg over 2 generations did not cause significant compound-related changes in reproductive or developmental parameters in rats. PMID- 11780959 TI - Cisplatin exposure induces mitochondrial toxicity in pregnant rats and their fetuses. AB - High levels of cis-diamminedicholorplatinum II (cisplatin)-DNA adducts have previously been observed at term in mitochondrial DNA (mtDNA) from organs of pregnant rats, and from their offspring, after administration of a single injection of cisplatin 15 mg/kg body weight (bw) to the pregnant rat on day 18 of gestation. The consequences of such DNA damage may be clinically relevant as cisplatin is given to pregnant women discovered to have ovarian cancer during pregnancy. In this study, kidneys, livers, and brains of exposed pregnant rats and their offspring were examined for mitochondrial functional integrity. Consistent with previous literature, the most severe toxicity occurred in maternal kidney, where oxidative phosphorylation (OXPHOS) enzyme activities were significantly (approximately 50%) impaired for Complexes II, III, and IV, mtDNA levels in drug-exposed animals were higher than in the unexposed controls, and abnormal mitochondrial morphology was observed by transmission electron microscopy (TEM). In fetal kidneys and livers, cisplatin exposure did not alter mitochondrial morphology or mtDNA quantity, but specific activities of OXPHOS Complexes II and IV were significantly decreased. Fetal brain sustained no discernible mitochondrial toxicity. Therefore, cisplatin-induced mitochondrial toxicity in maternal rat kidney is severe, while damage to mitochondria in fetal kidney and liver, occurring as a result of the transplacental drug exposure, appears to be mild. PMID- 11780960 TI - Preputial separation and glans penis changes in normal growing Crj: CD (SD) IGS rats. AB - This study was designed to detect preputial separation and glans penis changes in normal growing SD rats. We examined the changes until 53 days after birth. The glans penis surface changed from a protruding os penis structure to a W shape, and from a W shape to a flattened surface with age. The protruding os penis structure changed gradually to the W shape from postnatal day (PND) 30, and all rats had the W shape by PND 35. The flattened surface was observed from PND 39, and all rats had this structure by PND 44. In all rats, the day of complete preputial separation exactly corresponded to the day of appearance of the flattened surface. PMID- 11780961 TI - In utero reproductive study in rats exposed to nonylphenol. AB - Alkylphenol ethoxylates are widely used non-ionic surfactants. Nonylphenol ethoxylate constitutes 82% of the production of all alkylphenol ethoxylates and the breakdown product of nonylphenol ethoxylate, nonylphenol (NP) has been shown to be estrogenic in both in vitro and in vivo screening assays. To determine the potential reproductive toxicity of NP, a one-generation in utero study was conducted. Rats were dosed from gestation day 11 through 18 with NP at 3, 15, or 75 mg/kg/day or diethylstilbestrol (DES) at 30 microg/kg/day. DES was used as a positive control. Both substances were given orally by gavage. Male offspring were sacrificed at postnatal day (PND) 11, 21, or 110 and reproductive parameters were evaluated. Pup birth weight and body weight and percent motile sperm at age of 110 day were significantly reduced by DES. The absolute weight of the right epididymis was significantly reduced in the DES group. The absolute weight of the right epididymis were also significantly decreased in the animals exposed to 75 or 15 mg/kg/day NP, effects which disappeared when organ weight was related to body weight. This study showed a dose-dependent effect of nonylphenol on male reproductive development at doses of 75 and 15 mg/kg bw/day based on absolute epididymal weight. PMID- 11780962 TI - Placental transfer of the estrogenic mycotoxin zearalenone in rats. AB - In order to study the possible placental transfer of the Fusarium mycotoxin zearalenone (ZON), Sprague Dawley rats were treated with a single dose (0.74 mg/kg b.w.) of ZON i.v. on day 12 or day 18 of pregnancy, or intragastrically (i.g.) on day 18 of pregnancy. Samples of placenta, foetus, and maternal liver and spleen were collected for chemical analyses 0.3 h after treatment on day 12, and 0.3, 4, and 24 h after treatment on day 18. Three rats were used for each pregnancy day, administration route, and exposure time. The concentrations of ZON and its metabolites alpha- and beta-zearalenol (-ZOL) were determined quantitatively by high-performance liquid chromatography (HPLC) after incubation with beta-glucuronidase and purification on immunoaffinity columns. Tissue distribution was studied by means of whole body autoradiography at 4 and 24 h after treatment with tritiated ZON (750 microCi/kg b.w; 7.4 mg/kg b.w.) on day 18 of pregnancy. ZON and alpha-ZOL were transferred into the foetus on both gestational days. However, a delay in distribution into the foetus, relative to the maternal tissue, was observed. Beta-ZOL was below the detection limit in the foetus. No specific site of foetal accumulation of ZON or its metabolites was apparent. In the maternal tissues, the highest levels of ZON and of alpha- and beta-ZOL were found in the liver. PMID- 11780963 TI - Differential effects of octylphenol, 17beta-estradiol, endosulfan, or bisphenol A on the steroidogenic competence of cultured adult rat Leydig cells. AB - In the current studies, we evaluated the effects of 4-tert-octylphenol (OP), endosulfan, bisphenol A (BPA), and 17beta-estradiol on basal or hCG-stimulated testosterone formation by cultured Leydig cells from young adult male rats. Exposure of Leydig cells to increasing concentrations of OP (1 to 2000 nM), 17beta-estradiol (1 to 1000 nM), endosulfan (1 to 1000 nM) or BPA (1 to 1000 nM), alone or with 10 mIU/mL hCG for 4 or 24 h, did not lower ambient testosterone levels, although cells exposed to higher OP concentrations + hCG for 24 h often had modest declines in testosterone (10 to 20%). Of interest, exposure to the highest concentration OP (2000 nM) alone for 4 or 24 h increased testosterone levels (approximately 2-fold in 4-h exposed cells). Whether prior exposure to OP + hCG for 24 h affects the subsequent conversion of steroid substrates to testosterone over 4 h was evaluated. Progressive declines in 1 microM 22(R) hydroxycholesterol, 1 microM pregnenolone, or 1 microM progesterone conversion to testosterone was observed beginning at 100 to 500 nM OP exposure (maximal declines of 40 to 12% of controls were observed); however, the conversion of 1 microM androstenedione to testosterone was not affected by OP. These results suggested that 24-h exposure to OP + hCG has no effect on 17beta-hydroxysteroid dehydrogenase, which converts androstenedione to testosterone, but that it inhibits the 17alpha-hydroxylase/C17-20 lyase step, which converts progesterone to androstenedione. In addition, potentially, OP could inhibit cholesterol side/chain cleavage activity, which converts cholesterol to pregnenolone, and/or 3beta-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone. Of interest, exposure to increasing concentrations of 17beta-estradiol (1 to 1000 nM), endosulfan (1 to 1000 nM), or BPA (1 to 1000 nM) + hCG for 24 h had no effect on subsequent conversion of 22(R)hydroxycholesterol to testosterone. Furthermore, the inhibiting effects of OP + hCG exposure on subsequent conversion of progesterone to testosterone was unaffected by concomitant exposure to the pure estrogen antagonist, ICI 182,780, or the antioxidants, ascorbate or dimethyl sulfoxide, suggesting that the actions of OP are not mediated through binding to estrogen receptor alpha or beta or by free radical induced damage to steroidogenic enzymes, respectively. These results demonstrate that direct exposure of adult Leydig cells to OP may have subtle effects on their ability to produce testosterone, which may not be detected by measuring ambient androgen levels. In addition, the effects of OP on Leydig cell testosterone formation appear to be different from those of the native estrogen, 17beta-estradiol, and from other reported weak xenoestrogens such as endosulfan and BPA. PMID- 11780964 TI - Current trends in differential expression proteomics: isotopically coded tags. AB - Isotopically coded tag methodology holds significant promise for differential expression proteomic experiments. This methodology has the potential for high sensitivity, high coverage, and high throughput. Although significant technical advances have been made in the past year, this approach must be viewed as an emerging technique. Advances in sample fractionation, both at the protein and peptide level, and improved data acquisition schemes, will all be required before the full potential of the method is realized. PMID- 11780965 TI - Matching peptide mass spectra to EST and genomic DNA databases. AB - The use of mass spectrometry data to search molecular sequence databases is a well-established method for protein identification. The technique can be extended to searching raw genomic sequences, providing experimental confirmation or correction of predicted coding sequences, and has the potential to identify novel genes and elucidate splicing patterns. PMID- 11780966 TI - Exploring the protein interactome using comprehensive two-hybrid projects. AB - Large-scale two-hybrid projects were used in an approach to examine protein protein interactions. Despite the various limitations of this approach, these projects revealed a wealth of novel interactions, and the protein interactome may be much larger than expected. PMID- 11780967 TI - BIA-MS-MS: biomolecular interaction analysis for functional proteomics. AB - One of the experimental processes of functional proteomics is the analysis of protein interaction. Here, we review a new analytical platform, BIA-MS, for protein interaction analysis. BIA-MS is an integration of a surface plasmon resonance biosensor for real-time interaction analysis and mass spectrometry for the subsequent identification of interacting molecules. PMID- 11780968 TI - What place for polyacrylamide in proteomics? AB - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) continues to deliver high quality protein resolution and dynamic range for the proteomics researcher. To remain as the preferred method for protein separation and characterization, several key steps need to be implemented to ensure quality sample preparation and speed of analysis. Here, we describe the progress made towards establishing 2D PAGE as the optimal separation tool for proteomics research. PMID- 11780969 TI - Solution and chip arrays in protein profiling. AB - The industrialization of proteomics demands reproducible, robust and high throughput profiling technologies that current two-dimensional gel electrophoresis cannot achieve. New technologies in protein arrays, either on chips or with self-encoded elements in solution, hold much promise for interrogating the diverse and immense proteome. PMID- 11780970 TI - Cancer proteomics: from signaling networks to tumor markers. AB - Along with the great strides that have been made towards understanding cancer, has come a realization of the complexity of molecular events that lead to malignancy. Proteomics-based approaches, which enable the quantitative investigation of both cellular protein expression levels and protein-protein interactions involved in signaling networks, promise to define the molecules controlling the processes involved in cancer. PMID- 11780971 TI - Proteomics of multiprotein complexes: answering fundamental questions in neuroscience. AB - Proteomics tools offer new ways to analyse networks of proteins that control important neurobiological phenomena such as learning and memory. In this review, we discuss how a combined proteomic, pharmacological and genetic approach reveals that multiprotein complexes process neural information and encode memories. Simultaneous analysis of multiple proteins enables the development of new concepts and approaches for neuroscience research. PMID- 11780972 TI - Peptidomics technologies for human body fluids. AB - Peptides play a central role in many physiological processes. In order to analyse comprehensively all peptides and small proteins of a whole organism or a subsystem (peptidome), the use of technologies other than 2D gel electrophoresis is necessary. Approaches that use liquid chromatography or affinity purification and mass spectrometric identification have now been developed and applied successfully to the analysis of human body fluids. PMID- 11780973 TI - Insights into protein function through large-scale computational analysis of sequence and structure. AB - Functional genomic and proteomic technologies are producing biological data relating to hundreds, or even thousands of proteins per experiment. Rapid and accurate computational analysis of the molecular function of these proteins is therefore crucial in order to interpret these data and prioritize further experiments. PMID- 11780974 TI - High-throughput structural proteomics using x-rays. AB - Following the recent sequencing of the human genome, the focus has shifted from the DNA level to the protein level, with the goal of elucidating function. Technical developments in x-ray crystallography mean that the crystal structures of these new proteins can now been determined at an unprecedented rate, which assists in functional analysis and rational drug-design programmes. PMID- 11780975 TI - Of human patients. PMID- 11780976 TI - Another view. PMID- 11780977 TI - North Carolina law. PMID- 11780978 TI - Virtual reality glasses. PMID- 11780979 TI - Amalgam restorations. PMID- 11780980 TI - Amalgam supporter. PMID- 11780981 TI - Heart of the matter. PMID- 11780982 TI - Retiring JADA editor receives association's Distinguished Service Award. PMID- 11780983 TI - JADA author earns award. PMID- 11780984 TI - In your practice, have you experienced what you regard as insurance-industry intrusions on the relationship between you and your patients? PMID- 11780985 TI - The future of dentistry: an overview of a new report. AB - BACKGROUND AND OVERVIEW: The 2001 Future of Dentistry, or FOD, report was commissioned by the American Dental Association in 1999, developed by an oversight committee, and presented to the ADA House of Delegates in October 2001. The FOD report was intended to describe the current status of the U.S. dental profession, observe the recent trends that have guided the profession, envision challenges that the profession will face in the next five to 15 years and, finally, make recommendations about how to meet those challenges. This article presents a digest of some of the issues that are perceived to be of greatest interest and concern to the country's practicing dentists. CONCLUSIONS: The analyses in the FOD report lead to the conclusion that the profession is strong and healthy and that revolutionary changes are not necessary. Rather, a concerted effort to address the areas of concern is important to assure the American people of access to the finest dental health care possible. This will require the cooperation of all those involved in the delivery of dental care--not only the profession itself, but also industry, policy-makers and the public. CLINICAL IMPLICATIONS: The FOD report is a road map that will give every practitioner in his or her office more tools to provide the best care to the public. All of the recommendations--whether they involve education, research, finance or clinical practice--are meant to stimulate thoughts and actions that will help dentists and their patients in the pursuit of optimal oral health. PMID- 11780986 TI - Assessing the economic return of specializing in orthodontics or oral and maxillofacial surgery. AB - BACKGROUND: The authors determined the economic returns from an educational investment in the specialties of orthodontics and oral an maxillofacial surgery. They also addressed problems found in previous studies. METHODS: The marginal return for specializing in orthodontics or oral and maxillofacial surgery was determined using net present value and internal rate of return, or IRR, with the income of the general dentist serving as the common opportunity cost. Extreme scenario, threshold and one-way sensitivity analyses were used to account for variation in the data. RESULTS: The median group of orthodontists broke even 5.9 years after specialty training and had a working lifetime net return of $271,536 above that of general dentists; the IRR for them was 10.36 percent. The median group of oral and maxillofacial surgeons broke even 2.3 years after training and had a working lifetime net return of $587,563 above that of general dentists; the IRR for them was 25.30 percent. CONCLUSIONS: Under the most likely conditions, the authors found a positive economic return to dentists in both specialties from their additional dental training. PRACTICE IMPLICATIONS: The positive financial returns brought by specialization indicate that the demand for additional dental education should continue within an environment of increased educational investment costs. PMID- 11780987 TI - Effects of oral habits' duration on dental characteristics in the primary dentition. AB - BACKGROUND: Studies dating to the 1870s have demonstrated that long-term nonnutritive sucking habits may lead to occlusal abnormalities, including open bite and posterior crossbite. However, little is known as to whether habits of shorter durations have lasting effects. METHODS: The authors collected longitudinal data on nonnutritive sucking among children through a series of questionnaires regularly completed by parents. Researchers examined the children at ages 4 to 5 years and obtained study models. The models were measured for dental arch parameters (including arch width, arch length and arch depth) and assessed for overjet, overbite and posterior crossbite. The authors compared the dental arch and occlusal conditions among groups of children with nonnutritive sucking habits of different durations. RESULTS: Children with nonnutritive sucking habits that continued to 48 months of age or beyond demonstrated many significant differences from children with habits of shorter durations: narrower maxillary arch widths, greater overjet and greater prevalence of open bite and posterior crossbite. In addition, compared with those who ceased their habit by 12 months of age, those with habits at 36 months of age had significantly greater mandibular canine arch widths, maxillary canine arch depths and overjet, while those with habits at 24 months and 36 months had significantly smaller palatal depths. Prevalence of anterior open bite, posterior crossbite and excessive overjet (> 4 millimeters) increased with duration of habits. CONCLUSIONS: While continuous nonnutritive sucking habits of 48 months or longer produced the greatest changes in dental arch and occlusal characteristics, children with shorter sucking durations also had detectable differences from those with minimal habit durations. CLINICAL IMPLICATIONS: It may be prudent to revisit suggestions that sucking habits continued to as late as 5 to 8 years of age are of little concern. PMID- 11780988 TI - Examining the prevalence and characteristics of abfractionlike cervical lesions in a population of U.S. veterans. AB - BACKGROUND: Abfraction is believed to be caused by biomechanical loading forces. It may be due to flexure and ultimate fatigue of tooth tissues that occur away from the point of occlusal loading. Other possible causes of cervical lesions include toothbrush abrasion and erosion. The purpose of this study was to investigate the characteristics and prevalence of abfraction-like lesions in a population of U.S. veterans. METHODS: The authors evaluated 103 teeth with noncarious cervical lesions in 32 subjects and characterized them based on the surface on which the lesion was located, history of toothbrush abrasion, size of the lesion, presence of plaque, surface texture, and presence and size of occlusal wear facets. RESULTS: Clinical examination revealed that adjacent control teeth had a significantly lower percentage of surfaces with plaque than did teeth with cervical lesions. Control teeth also had significantly less gingival recession than did affected teeth. Seventy-five percent of subjects reported a history of using a firm toothbrush, and 78.1 percent reported using a brushing technique that is known to cause toothbrush abrasion in the affected area. Affected teeth had neither significantly different occlusal wear facets nor occlusal contacts than control teeth. No significant correlations were found between cervical lesion dimensions and facet area. CONCLUSIONS: Toothbrush abrasion is strongly suspected as contributing to the formation of the majority of wedge-shaped lesions in this group of subjects. A small subset of lesions is thought to have resulted from some other phenomenon. Although the presence or contribution of occlusal stresses in the direct formation of these lesions could not be measured directly, the possibility of abfraction could not be eliminated. CLINICAL IMPLICATIONS: Because the existence of abfraction could not be ruled out in about 15 percent of the cases, teeth with noncarious, wedge-shaped lesions warrant careful occlusal evaluation, with the possible need for occlusal adjustment or bitesplint therapy to treat bruxism. PMID- 11780990 TI - Acupuncture: a unique effort to treat periodontal disease. AB - BACKGROUND: Acupuncture, a technique for conscious sedation, was introduced as a modality for pain control in 1958 in the United States. It has been used to treat illnesses in Asia for more than 3,000 years. CASE DESCRIPTION: This case report describes the use of acupuncture as a treatment for periodontal disease as prescribed and administered by a Korean practitioner. The patient was treated in 1991 by the insertion of multiple acupuncture needles in response to a diagnosis of "gum pain." Chronic, low-grade discomfort, diagnosed as a symptom of the disease, disappeared after the acupuncture treatment. The patient had minimal professional care in this country since the acupuncture therapy. She had experienced low-grade, but persistent, discomfort over the previous two years. CLINICAL IMPLICATIONS: The oral diagnosis is moderate to advanced generalized chronic periodontitis with primary occlusal trauma. The present findings tend to implicate parafunction as the etiology for the current pain and perhaps the etiology for the discomfort experienced 10 years ago. PMID- 11780989 TI - Complications of an intra-arterial injection from an inferior alveolar nerve block. AB - BACKGROUND: Unintended intravascular injections from inferior alveolar nerve blocks result in frustrating complications, both systemically and locally. It is imperative that the dentist diagnose the complication and treat it appropriately. Sometimes, several reactions occur simultaneously. CASE DESCRIPTION: The authors present a case report that illustrates some of the many complications resulting from inferior alveolar nerve block injections. In this case, complications developed from intra-arterial injection of local anesthetic. The facial skin, intraoral structures and eye were affected. Within 60 minutes of the injection, all structures returned to their normal state. Prompt diagnosis and reassurance usually calm the patient. CLINICAL IMPLICATIONS: Even when clinicians use the utmost care, by aspirating before the injection and noting anatomical landmarks, intra-arterial injections can occur during inferior alveolar nerve blocks. Fortunately, permanent damage to nerves, facial and oral tissues, and eyes is rare. The practitioner should diagnose and treat the problems appropriately to avoid any irreversible complications. PMID- 11780992 TI - A time-saving technique for making accurate temporary restorations. PMID- 11780991 TI - Chronic parotitis: diagnosis and treatment. AB - BACKGROUND: Chronic parotitis, or CP, is a nonspecific sialadenitis that often is seen first in the dental office. The cause, although not definitively determined, is most likely multifactorial and includes decreased salivation, stasis and an ascending retrograde duct infection. The authors present a case report to illustrate the symptomatology of CP to facilitate its differentiation from other entities that mimic CP. CASE DESCRIPTION: A 60-year-old woman with a 30-year history of recurrent swellings of her left parotid gland was diagnosed with CP. The diagnosis was based on history, clinical examination, salivary volume and chemistry, computerized tomographic scan and sialography. Treatment was palliative in nature. CLINICAL IMPLICATION: As a member of the health care team, the dentist must be familiar with the various causes of recurrent parotid infections. Early clinical recognition of CP leads to appropriate and successful care. PMID- 11780993 TI - Evaluation of a transoral delivery system for topical anesthesia. AB - BACKGROUND: The development of bioadhesives has allowed for the creation of a novel transoral topical anesthesia delivery system used to alleviate pain by needlestick injections and select dental procedures. METHODS: Sixty subjects evaluated the effectiveness of a lidocaine-containing bioadhesive patch, or L-BP, to alleviate pain caused by needlesticks, or Ns, with or without injection, and with scaling and root planing, or Sc/RP, instrumentation. The authors topically administered a commonly used benzocaine-containing gel, or B-G, preparation to analogous sites for direct comparison. Subjects rated their degree of pain/discomfort using verbal pain score, or VPS, measurements. RESULTS: Paired t tests and signed ranked tests revealed that the subjects' perception of pain was significantly reduced after the application of L-BP with placebo (P < .01) for both Ns and Sc/RP but was not significantly reduced by B-G with placebo. L-BP also significantly reduced the subjects' perception of pain caused by Ns and Sc/RP when compared directly with B-G (P < .01). The resultant tissue anesthesia by L-BP significantly reduced pain to Ns with or without anesthetic injection using 25- and 27-gauge needles. However, Ns in conjunction with anesthetic injections generated significantly greater pain than that caused by Ns alone (P < .01). VPS score differences between 25- and 27-gauge needles were not found. CONCLUSIONS: This study found that a lidocaine-containing bioadhesive system delivering topical anesthesia was highly effective in alleviating pain/discomfort arising from Ns, with and without concomitant injection, and select Sc/RP procedures. CLINICAL IMPLICATIONS: A new topical delivery system that effectively anesthetizes oral tissues may prove highly useful in allaying patient anxieties about and fear of select dental procedures. PMID- 11780994 TI - Artificial salivas. Xerostomia. PMID- 11780995 TI - Dental continuing education in the aftermath of Sept. 11. AB - The American people and our profession have been dealt a traumatic blow. The short-term effects of this incident are obvious: all aspects of our economy have slowed; travel and dental CE attendance are down; dentists are seeking other modes of CE that do not require travel. As the country recovers, I predict that dental CE will have a temporary lull, but that the desire for dental CE will continue to expand, and that the destination and local courses to which we have been accustomed will flourish again. PMID- 11780996 TI - Scientific debate and the First Amendment. PMID- 11780997 TI - Relative roles of microdamage and microfracture in the mechanical behavior of trabecular bone. AB - Compared to trabecular microfracture, the biomechanical consequences of the morphologically more subtle trabecular microdamage are unclear but potentially important because of its higher incidence. A generic three-dimensional finite element model of the trabecular bone microstructure was used to investigate the relative biomechanical roles of these damage categories on reloading elastic modulus after simulated overloads to various strain levels. Microfractures of individual trabeculae were modeled using a maximum fracture strain criterion, for three values of fracture strain (2%, 8%, and 35%). Microdamage within the trabeculae was modeled using a strain-based modulus reduction rule based on cortical bone behavior. When combining the effects of both microdamage and microfracture, the model predicted reductions in apparent modulus upon reloading of over 60% at an applied apparent strain of 2%, in excellent agreement with previously reported experimental data. According to the model, up to 80% of the trabeculae developed microdamage at 2% apparent strain, and between 2% and 10% of the trabeculae were fractured, depending on which fracture strain was assumed. If microdamage could not occur but microfracture could, good agreement with the experimental data only resulted if the trabecular hard tissue had a fracture strain of 2%. However, a high number of fractures (10% of the trabeculae) would need to occur for this case, and this has not been observed in published damage morphology studies. We conclude therefore that if the damage behavior of trabecular hard tissue is similar to that of cortical bone, then extensive microdamage is primarily responsible for the large loss in apparent mechanical properties that can occur with overloading of trabecular bone. PMID- 11780998 TI - The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur. AB - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF I by ovarian steroids is well known, however, their effect on local GH and IGF-I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF-I levels as well as on bone density in the rat. Nine month-old rats were ovariectomized (OVX) or sham operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17beta-estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF-I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF-I levels. Estradiol treatment increased femur GH and IGF-I levels compared to SHAM rats. Progesterone restored GH and increased IGF-I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF-I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone. PMID- 11780999 TI - Immature osteoblastic cells express the pro-alpha2(XI) collagen gene during bone formation in vitro and in vivo. AB - Type XI collagen is predominantly found in cartilage. However, expression of the pro-alpha2(XI) collagen gene (COL11A2) has recently been detected in various non cartilaginous tissues. We identified the differentiation stage at which COL11A2 was expressed in cultured fetal rat calvarial (FRC) cells and in rat femoral fracture calluses in order to investigate the involvement of COL11A2 during bone formation in vitro and in vivo. We also studied the alternative splicing of exons 6-8 in FRC cells and fracture calluses. In FRC cells, mineralized nodules stained with von Kossa stain were observed from day 9 after confluence. COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis. During rat femoral fracture repair, intramembranous ossification proceeded and newly formed woven bone was observed on the cortex on day 7 after fracture. In situ hybridization showed that COL11A2 signals were detected in osteoblastic cells in the newly formed woven bone. According to the maturation and remodeling of the woven bone into the trabecular bone, the distribution of the signal for COL11A2 mRNA was limited to the superficial osteoblastic cells of the newly formed trabecular bone. These results demonstrated that COL11A2 was expressed in relatively immature osteoblastic cells during bone formation in vitro and in vivo. RT-PCR showed that the shortest band corresponding to mRNA lacking exons 6-8 was clearly detected when using RNA from soft calluses. In contrast, the largest band corresponding to mRNA with exons 6-8 was predominant when using RNA from FRC cells or from hard calluses on days 7 and 14. These results indicate that the splicing pattern of exons 6-8 in osteoblastic cells is different from the pattern in chondrocytes. PMID- 11781000 TI - The role of collagen in determining bone mechanical properties. AB - The hypothesis of this study was that collagen denaturation would lead to a significant decrease in the toughness of bone, but has little effect on the stiffness of bone. Using a heating model, effects of collagen denaturation on the biomechanical properties of human cadaveric bone were examined. Prior to testing, bone specimens were heat treated at varied temperatures (37-200 degrees C) to induce different degrees of collagen denaturation. Collagen denaturation and mechanical properties of bone were determined using a selective digestion technique and three-point bending tests, respectively. The densities and weight fractions of the mineral and organic phases in bone also were determined. A repeated measures analysis of variance showed that heating had a significant effect on the biomechanical integrity of bone, corresponding to the degree of collagen denaturation. The results of this study indicate that the toughness and strength of bone decreases significantly with increasing collagen denaturation, whereas the elastic modulus of bone is almost constant irrespective of collagen denaturation. These results suggest that the collagen network plays an important role in the toughness of bone, but has little effect on the stiffness of bone, thereby supporting the hypothesis of this study. PMID- 11781001 TI - Shape and size of isolated bone mineralites measured using atomic force microscopy. AB - The inorganic phase of bone is comprised primarily of very small mineralites. The size and shape of these mineralites play fundamental roles in maintaining ionic homeostasis and in the biomechanical function of bone. Using atomic force microscopy, we have obtained direct three-dimensional visual evidence of the size and shape of native protein-free mineralites isolated from mature bovine bone. Approximately 98% of the mineralites are less than 2 nm thick displaying a plate like habit. Distributions of both thickness and width show single peaks. The distribution of lengths may be multimodal with distinct peaks separated by approximately 6 nm. Application of our results is expected to be of use in the design of novel orthopaedic biomaterials. In addition, they provide more accurate inputs to molecular-scale models aimed at predicting the physiological and mechanical behavior of bone. PMID- 11781002 TI - Subchondral bone thickness, hardness and remodelling are influenced by short-term exercise in a site-specific manner. AB - It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Adjacent osteochondral samples from each test site underwent histomorphometric analysis (for subchondral bone thickness, osteoid perimeter, osteoid seam width, eroded cavity area and eroded cement line surface length) and microhardness testing. Bone from horses undergoing high intensity training was thicker with a greater osteoid perimeter, and at individual sites had a smaller osteoid seam width and eroded cavity. Exercise-related differences were most marked at dorsal locations. Maximal differences in bone formation indices were observed at dorsal radial and medial third carpal locations. Overall subchondral bone from dorsal sites was thicker with a greater osteoid perimeter. Subchondral bone from dorsal sites was approximately 35% harder than bone from palmar sites. These results show topographical variations in subchondral bone structure, formation, resorption and material properties and a site-specific response to exercise. The maximal response to exercise was at high load sites with a clinical predisposition to injury. These findings indicate that the combined effect of exercise and local load variations within a joint may lead to maximal adaptive responses or overload of these responses at sites predisposed to injury. PMID- 11781003 TI - Tensile properties of the physis vary with anatomic location, thickness, strain rate and age. AB - The variable outcome of physeal distraction has raised questions as to the mechanism by which bone lengthening is achieved. Is it by stretching of the matrix or does it stimulate growth? In order to explore the contribution of matrix stretching, we sought to answer the following questions in an animal model: (a) Are the tensile properties of the lateral side of the proximal tibial physis different from the medial? (b) Are the tensile properties strain-rate dependent? (c) Does the growth plate fracture through any preferred zone in tension? (d) Are the tensile properties of the bovine growth plate a function of age? (e) Are thicker growth plates weaker in tension? (f) Are the tensile properties of the bovine growth plate comparable to those of a child's? We compared bone-cartilage-bone specimens (0.5 x 2.5 mm2 in cross-section) from the lateral, central and medial regions of the proximal tibial growth plates of 12- to 18-month heifers. 70 specimens were tested to failure in tension at 0.0004, 0.004 and 0.04 mm/s. Tensile strength and tangent modulus were 33% and 25% greater, respectively, on the lateral side compared with the medial, and both were increased at the higher strain rates. We found no difference in the ultimate strains by region or strain rate. Thicker growth plates were weaker. Scanning electron microscopy revealed a three-dimensional fracture pattern extending from the upper columnar into the reserve zone. Bundles of intact chondrons remained intact, but only on the metaphyseal side, having been torn from an interterritorial matrix which remained mostly on the epiphyseal side of the fracture. We compared 21 specimens of 12- to 18-month and 19 specimens of 5-month calves from similar regions of the proximal tibia. These were tested to failure in tension at 0.004 mm/s. The older bovine growth plate was 25% thinner, 34% stronger and failed at 65% greater strain. For comparison, we tested eight samples from the femoral capital growth plate of two cerebral palsy patients. These were twice as thick as our bovine samples and about half as strong, but with similar ultimate strain values. PMID- 11781004 TI - Weight-bearing alters the expression of collagen types I and II, BMP 2/4 and osteocalcin in the early stages of distraction osteogenesis. AB - This study was performed to investigate the effect of loading on the biology of newly forming bone during limb lengthening. Unilateral 2.0 mm femoral lengthenings were performed in 20 male Sprague Dawley rats. Half (n = 10) of the animals were allowed to bear weight freely, while the other half were prevented from weight-bearing via an ipsilateral through-knee amputation. The animals in each group were sacrificed after one (n = 5) or four (n = 5) days of consolidation (post-operative days seven and 10, respectively). In situ hybridization for osteocalcin and collagen I, and antibody staining for collagen II and BMP 2/4 were used to evaluate the molecular influence of loading. There was more new bone in the distraction gap of the weight-bearing animals than there was in the non-weight-bearing animals. BMP 2/4 expression, and the messages for collagen I and osteocalcin, were more abundant in tissue from the weight-bearing animals; collagen II was higher in the non-weight-bearing animals. This suggests that early regenerate tissue is capable of responding to loading, and that weight bearing appears to stimulate intramembranous ossification. These findings support the concept of early weight-bearing after limb lengthening. PMID- 11781005 TI - The angiogenic response to skeletal injury is preserved in the elderly. AB - Angiogenesis is essential for normal bone formation and repair. Avascularity characterizes aberrant fracture union in the elderly, while angiogenic mechanisms during cutaneous wound repair are attenuated in aged humans. We hypothesized that skeletal injury results in local (circulating) and systemic (fracture site) 'angiogenic' responses and that these reparative mechanisms are attenuated with advanced patient age. This prospective study examined peripheral blood and fracture hematoma from 32 patients, 16 under 40 years and 16 over the age of 75, undergoing emergent surgery for isolated fracture. The angiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were assayed. Endothelial cell cultures were supplemented with patient plasma and fracture hematoma and angiogenesis determined in vitro by measuring cell proliferation and blood vessel tube formation. Angiogenesis was determined in vivo using a murine dorsal wound pocket model and quantification of new blood vessel formation after 7 days. We found that all injured patients, irrespective of age, have elevated plasma and fracture hematoma levels of VEGF and PDGF. These elevated cytokine concentrations translate into biologically significant angiogenic effects, in vitro and in vivo. These effects are primarily VEGF mediated and are not dependent on patient age. The biological activity of these growth factors does not diminish with advanced age. Thus skeletal injury does result in local and systemic angiogenic responses whereby angiogenic cytokine availability and activity is preserved in the aged suggesting alternative mechanisms for the development of avascularity in delayed and fracture non-union in the elderly. PMID- 11781006 TI - Mechanobiology of initial pseudarthrosis formation with oblique fractures. AB - Mechanical stresses play an important role in regulating tissue differentiation in a variety of contexts during skeletal development and regeneration. It has been shown that some intermittent loading at a fracture site can accelerate secondary fracture healing. However, it has not been shown how the stress and strain histories resulting from mechanical loading of a fracture might, in some cases, inhibit normal fracture healing and induce pseudarthrosis formation. In this study, finite element analysis is used to calculate hydrostatic stress and maximum principal tensile strain patterns in regenerating tissue around the site of an oblique fracture. Using a mechanobiologic view on tissue differentiation, we compared calculated stress and strain patterns within the fracture callus to the histomorphology of a typical oblique pseudarthrosis. Tissue differentiation predictions were consistent with the characteristic histomorphology of oblique pseudarthrosis: in the interfragmentary gap. tensile strains led to "cleavage" of the callus; at the ends of both fracture fragments, hydrostatic pressure and tensile strain caused fibrocartilage formation, and, at discrete locations of the periosteum at the oblique fracture ends, mild hydrostatic tension caused bone formation. We also found that discrete regions of high hydrostatic pressure correlated with locations of periosteal bone resorption. When previous findings with distraction osteogenesis are considered with these observations, it appears that low levels of hydrostatic pressure may be conducive to periosteal cartilage formation but high hydrostatic pressure may induce periosteal bone resorption during bone healing. We concluded that tissue differentiation in pseudarthrosis formation is consistent with concepts previously presented for understanding fracture healing, distraction osteogenesis, and joint formation. PMID- 11781007 TI - Direction-dependent resistance to flow in the endplate of the intervertebral disc: an ex vivo study. AB - A comparison of the higher hydrostatic pressure in the nucleus of the healthy intervertebral disc during daily loading with the relatively lower osmotic swelling pressure in the disc during rest suggests the existence of direction dependent flow resistance such that all of the fluid exuded from the disc during loading is recovered during rest. In this study, this direction-dependent resistance was demonstrated for flows through the cartilage endplates and the underlying marrow contact channels in the bony endplates. Using an ex vivo sheep endplate model, the resistance ratio (Rout/Rin) for flow through the endplate was 39.0+/-3.8 (mean +/- S.E.). In addition, a path of fluid flow through the marrow contact holes was revealed using fluorescent staining. PMID- 11781008 TI - Characterization of nucleus pulposus-like tissue formed in vitro. AB - In order to be able to study the metabolism of nucleus pulposus (NP) tissue, we developed a cell culture system that resulted in the formation of NP-like tissue in vitro. NP cells were isolated from sheep lumbar spines and grown on filter inserts (Millicell CM). Histological examination showed that the cells accumulated extracellular matrix and formed a continuous layer of NP-like tissue. The accumulation of sulfated proteoglycans in the NP-like tissue continued up to 10 weeks and this was paralleled by an increase in tissue thickness and dry weight. DNA content remained stable during the first 4 weeks but then decreased over time. The amount of DNA, glycosaminoglycan (GAG) and collagen per mg dry weight of the tissue generated after 10 weeks in culture were 1.25+/-0.02, 301.6+/-27.7 and 411+/-65 microg, respectively, compared with 1.04+/-0.08, 320.6+/-21.2 and 399+/-4.4 microg (mean +/- SEM) for the in vivo tissue. There was no significant difference between in vitro and in vivo tissue. The cells in culture synthesized large proteoglycans (kav = 0.26+/-0.03, mean +/- S.D.) which were similar in size to those synthesized by cells in NP tissue in ex vivo culture (kav = 0.22+/-0.02, mean +/- S.D.) as determined by Sepharose CL-2B column chromatography. The in vitro generated tissue contained type II collagen as demonstrated by sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) and silver staining as well as Western blot analysis. NP cells grown on filters generate tissue similar in composition to the in vivo tissue, for the characteristics examined to date, and should be a suitable model to use to study NP metabolism and extracellular matrix turnover. PMID- 11781009 TI - Involvement of BMP-2 signaling in a cartilage cap in osteochondroma. AB - This study describes the distributions of bone morphogenetic protein (BMP)-2 as well as mRNAs for BMP receptor type IB (BMPRIB). collagen types II (Col II) and III (Col III) in a growing "cartilage cap" of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP-2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP-2 signaling in the pathogenesis of cartilage cap of osteochondroma. and suggests the role of BMP-2 in the growth of cartilage cap in osteochondroma. PMID- 11781010 TI - Integration of engineered cartilage. AB - The structure and function of cartilaginous constructs, engineered in vitro using bovine articular chondrocytes, biodegradable scaffolds and bioreactors, can be modulated by the conditions and duration of tissue cultivation. We hypothesized that the integrative properties of engineered cartilage depend on developmental stage of the construct and the extracellular matrix content of adjacent cartilage, and that some aspects of integration can be studied under controlled in vitro conditions. Disc-shaped constructs (cultured for 5+/-1 days or 5+/-1 weeks) or explants (untreated or trypsin treated cartilage) were sutured into ring-shaped explants (untreated or trypsin treated cartilage) to form composites that were cultured for an additional 1-8 weeks in bioreactors and evaluated biochemically, histologically and mechanically (compressive stiffness of the central disk, adhesive strength of the integration interface). Immature constructs had poorer mechanical properties but integrated better than either more mature constructs or cartilage explants. Integration of immature constructs involved cell proliferation and the progressive formation of cartilaginous tissue, in contrast to the integration of more mature constructs or native cartilage which involved only the secretion of extracellular matrix components. Integration patterns correlated with the adhesive strength of the disc-ring interface, which was markedly higher for immature constructs than for either more mature constructs or cartilage explants. Trypsin treatment of the adjacent cartilage further enhanced the integration of immature constructs. PMID- 11781011 TI - Controlled-release of IGF-I and TGF-beta1 in a photopolymerizing hydrogel for cartilage tissue engineering. AB - Photopolymerizing hydrogel systems provide a method to encapsulate cells and implant materials in a minimally invasive manner. Controlled release of growth factors in the hydrogels may enhance the ability to engineer tissues. IGF-I and TGF-beta1 were loaded in PLGA microspheres using a double emulsion technique. 125 ng and 200 pg of active IGF-I and TGF-beta, respectively, as measured by ELISA, were released over 15 days. The growth factor containing microspheres were photoencapsulated with bovine articular chondrocytes in PEO-based hydrogels and incubated in vitro for two weeks. Statistically significant changes in glycosaminoglycan (GAG) production compared to control gels either without microspheres or with blank spheres were observed after a 14 day incubation with IGF-I and IGF-I/TGF-beta microspheres combined, with a maximum density of 8.41+/ 2.5% wet weight GAG. Total collagen density was low and decreased with the IGF I/TGF-beta microspheres after two weeks incubation, but otherwise remained unchanged in all other experimental groups. Cell content increased 10-fold to 0.18+/-0.056 x 10(6) cells/mg wet weight and extracellular matrix (ECM) staining by H&E increased in hydrogels with IGF-I/TGF-beta microspheres. In conclusion, photoencapsulation of microspheres in PEO-based hydrogels provides a method to deliver molecules such as growth factors in porous hydrogel systems. PMID- 11781012 TI - Integrative cartilage repair: adhesive strength is correlated with collagen deposition. AB - Procedures to repair focal articular cartilage defects often result in poor integration between the host cartilage and the graft tissue, and this may be related to the lack of matrix deposition and the death of chondrocytes near a cut cartilage surface. The objective of this study was to determine if cartilage repair was related to deposition of newly synthesized collagen. The mechanical integration that occurred between two live adult bovine cartilage blocks cultured in partial apposition for two weeks was correlated with [3H]proline incorporation, a measure of protein synthesis, of which more than 66% was accounted for by collagen. A similar level of mechanical integration occurred in sample pairs consisting of a live and killed cartilage block, and this adhesive strength was also correlated with [3H]proline deposition into both the live and the killed blocks. In these samples, the [3H]proline deposited into the killed cartilage appeared to originate from chondrocytes in the live cartilage, since live cells were not detected in the killed cartilage block by either viability staining or [35S]sulfate incorporation. These results suggest a mechanism of integrative cartilage repair in which live chondrocytes within cartilage secrete matrix molecules that are components of a collagen network, and subsequent deposition of these molecules near the repair interface contributes to functional integration. PMID- 11781013 TI - Compressive properties and function-composition relationships of developing bovine articular cartilage. AB - The composition of cartilage is known to change during fetal and postnatal development. The objectives of this study were to characterize the compressive biomechanical properties of the 1 mm thick articular layer of cartilage of the distal femur from third-trimester bovine fetuses, from 1 to 3 week old bovine calf and from young adult bovine knees, and to correlate these properties with tissue components. The confined compression modulus increased 180% from the fetus to the calf and adult. The hydraulic permeability at 45% offset compression (relative to the free-swelling thickness) decreased by 70% from fetus to adult. These development-associated changes in biomechanical properties were primarily associated with a marked (approximately 2-3-fold) increase during development in collagen content and no detectable change in glycosaminoglycan (GAG) content. A role for collagen in the compressive properties of cartilage and the gradual increase in collagen during development suggest that collagen metabolism is critical for cartilage tissue engineering and repair therapies. PMID- 11781014 TI - Mechanisms of chondrocyte adhesion to cartilage: role of beta1-integrins, CD44, and annexin V. AB - The initial adhesion of transplanted chondrocytes to surrounding host cartilage may be important in the repair of articular defects. Adhesion may position cells to secrete molecules that fill the defect and integrate repair tissue with host tissue. While chondrocytes are known to become increasingly adherent to cartilage with time, the molecular basis for this is unknown. The objective of this study was to investigate the role of beta1-integrin, CD44, and annexin V receptors in chondrocyte adhesion to cartilage. Chondrocytes were cultured in high density monolayer, released with trypsin, and allowed to recover in suspension for 2 h at 37 degrees C. Under these conditions, flow cytometry analysis showed that chondrocytes expressed beta1-integrins, CD44, and annexin V. In a rapid screening assay to assess chondrocyte adhesion to cartilage, cell detachment decreased from 79% at 10 min following transplantation to 10% at 320 min. Treatment of cells with a monoclonal antibody to block beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls. Similarly, results from a parallel-plate shear flow adhesion assay showed that blocking beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls at each level of applied shear (0-70 Pa). In both assays, treatment of cells with reagents that block CD44 (hyaluronan oligosaccharides or monoclonal Ab IM7) or annexin V (polyclonal Ab #8958) had no detectable effect on adhesion. With cartilage treated with chondroitinase ABC, blocking beta1-integrins also increased chondrocyte detachment, while blocking CD44 and annexin V also had no detectable effect. Under the conditions studied here, beta1-integrins appear to mediate chondrocyte adhesion to a cut cartilage surface. Delineation of the mechanisms of adhesion may have clinical implications by allowing cell manipulations or matrix treatments to enhance chondrocyte adhesion and retention at a defect site. PMID- 11781015 TI - Deformation and rupture of the articular surface under dynamic and static compression. AB - Cartilage-on-bone samples were dynamically and statically compressed at various stress levels to determine the deformation and rupture behaviour of the articular surface (AS). Instantaneous deformations were captured photographically by using a transparent indenter in combination with a ultra high speed flash. Principal strains (PS) were evaluated using large deformation theory. The tensile strains induced indirectly in the AS were a function of the rate at which the direct compressive force was applied. At the same compressive stress the tensile strains induced statically were approximately twice those induced dynamically. Rupture of the AS occurred in about 60% of those specimens tested statically at 15 MPa and followed approximately the split-line direction. By contrast, no rupture was observed dynamically even at stresses as high as 28 MPa. In terms of joint function the research demonstrates that the AS is considerably more resistant to rupture under dynamic than under static loading. The biomechanical parameter governing rupture appears to be the level of indirectly induced surface strain rather than the directly applied compressive stress. The very different mechanisms controlling the compressive deformation of articular cartilage (AC) at high vs low rates of loading clearly influence the levels of in-plane strain induced in the AS. PMID- 11781016 TI - Biosynthetic response and mechanical properties of articular cartilage after injurious compression. AB - Traumatic joint injury is known to produce osteoarthritic degeneration of articular cartilage. To study the effects of injurious compression on the degradation and repair of cartilage in vitro, we developed a model that allows strain and strain rate-controlled loading of cartilage explants. The influence of strain rate on both cartilage matrix biosynthesis and mechanical properties was assessed after single injurious compressions. Loading with a strain rate of 0.01 s(-1) to a final strain of 50% resulted in no measured effect on the cells or on the extracellular matrix, although peak stresses reached levels of about 12 MPa. However, compression with strain rates of 0.1 and 1 s(-1) caused peak stresses of approximately 18 and 24 MPa, respectively, and resulted in significant decreases in both proteoglycan and total protein biosynthesis. The mechanical properties of the explants (compressive and shear stiffness) were also reduced with increasing strain rate. Additionally, cell viability decreased with increasing strain rate, and the remaining viable cells lost their ability to exhibit an increase in biosynthesis in response to low-amplitude dynamic mechanical stimulation. This latter decrease in reparative response was most dramatic in the tissue compressed at the highest strain rates. We conclude that strain rate (like peak stress or strain) is an important parameter in defining mechanical injury, and that cartilage injuriously compressed at high strain rates can lose its characteristic anabolic response to low-amplitude cyclic mechanical loading. PMID- 11781017 TI - Gait analysis after total hip arthroplasty with leg-length equalization in women with unilateral congenital complete dislocation of the hip--comparison with untreated patients. AB - Patients with Crowe Type-IV congenital dislocation of the hip (CDH) show significant clinical improvement after total hip arthroplasty (THA) because this surgery greatly reduces pain. Concomitant leg-length equalization in unilateral patients--a controversial procedure--theoretically should significantly improve these patients' ability to walk efficiently and comfortably. To understand the impact of leg-length equalization on these patients, we compared their gait parameters with those of untreated patients without pain but with leg-length discrepancy. Using a motion analysis system, three force platforms and computer calculation, the gait parameters during level walking of 22 women with unilateral Crowe Type-IV CDH were studied at an average of 58 months (27-98 months) following a successful cementless THA. The socket was placed in the best bone stock, which was close to the level of the true acetabulum. The leg-length discrepancy was equalized to within 2 cm in all patients. The Harris hip score averaged 94.8 (range, 88-100) at the time of the study. Nine women with untreated unilateral Crowe Type-IV CDH without major pain but with an average leg-length discrepancy of 4.7 cm (range, 2.5-6 cm) were also studied for comparison. The treated subjects (Group 1; THA and leg-length equalization) walked faster and had gait parameters with better bilateral symmetry than the untreated subjects (Group 2). We concluded that leg-length equalization in addition to THA in patients with unilateral Crowe Type-IV CDH significantly improves gait symmetry and efficiency. PMID- 11781018 TI - Mixed-mode failure response of the cement-bone interface. AB - Mechanical failure of the cement-bone interface can contribute to clinical loosening of cemented total hip replacements. The conditions that cause loosening are poorly understood, in part, due to a lack of information on the mechanical behavior of the cement bone interface. The purpose of this study was to determine the mechanical behavior of the cement-bone interface due to mixed-mode (combined tension and shear) loading and to develop a failure model for the cement bone interface. Laboratory tests of machined cement-bone test specimens were performed with mixed-mode loading conditions (loading angles of 22.5 degrees, 45 degrees, and 67.5 degrees) to determine the mechanical response in the pre-yield and post yield state. After accounting for the quantity of interdigitated bone as a covariate, the mixed-mode data were combined with previous tension (0 degrees) and shear data (90 degrees) to develop a failure model for the cement bone interface. The strength of the interface was positively correlated with the quantity of interdigitated bone (r2 = 0.70, 0.53, 0.49, for 22.5 degrees, 45 degrees, and 67.5 degrees, respectively). There was a significant increase in failure strength (P < 0.001) with increasing mixed-mode angle. When all data were incorporated into an elliptical failure criterion, the average error between the actual and predicted strength was 33%. These results can now be incorporated into constitutive models of the cement bone interface to determine the initiation and progression of interface failure in cemented total hip replacements. PMID- 11781019 TI - Accuracy and precision of radiostereometric analysis in the measurement of THR femoral component translations: human and canine in vitro models. AB - Radiostereometric analysis (RSA) is used to measure translations of joint replacement components with respect to the host bone in vivo. We used two cadaveric models of hip arthroplasty, one human and one canine, to evaluate the accuracy and precision of RSA-based estimates of translations of the femoral component with respect to the femur under ideal conditions. The femoral components were attached rigidly to a micrometer stage that provided standard displacements in increments of 25 and 50 microm in the interval from zero to 500 microm along three orthogonal axes. Radiostereometric examinations were performed for each increment. Accuracy was calculated as the 95% prediction intervals from regression analyses between the measured and actual displacements. Precision was evaluated as the standard deviation of five repeated measurements of a 200 microm displacement along each axis. Both accuracy and precision were best along the longitudinal axis, with a prediction interval of +/-47 microm in the human model and +/-45 microm in the canine model and a standard deviation of 30 microm in the human model and 40 microm in the canine model. The use of only the prosthetic head as a landmark (as opposed to three markers placed on the femoral stem) led to a 3-fold larger prediction interval in the human model and a 2-fold greater prediction interval in the canine model. PMID- 11781020 TI - Inducible displacements of cemented tibial components during weight-bearing and knee extension observations during dynamic radiostereometry related to joint positions and 2 years history of migration in 16 TKR. AB - The inducible displacements of the tibial component caused by active extension were studied in 16 knees 1 yr after an AMK total knee arthroplasty with either flat. concave or posterior-stabilised (PS) designs of the joint area. Continuous change of the position of the tibial component occurred with proceeding extension. Rocking, subsidence and lift-off at different localisations were observed. In 3 of 4 knees with flat inserts the tibial component tilted anteriorly from 45 degrees to 35 degrees of flexion. A similar anterior tilt was seen in 2 of 6 with concave inserts and 5 of 6 with the PS design, but the tilting started later, when the knee had 5-20 degrees more extension. From 45-15 degrees of flexion most components tilted into valgus. Three knees (1 concave with, 1 concave without PCL and 1 PS) showed a sudden tilt into varus direction followed by a rocking motion in the opposite direction. The other types of displacements studied showed a more uniform pattern. The inducible maximum translation (MTPM) at 20 degrees of extension tended to be associated with increased migration between 0 and 2 yr when measured with the same parameter (Spearman's rho = 0.54, P = 0.03). Increased medial displacement of the center of the proximal tibia at 25 degrees was associated with increased anterior tilt. This type of motion was most commonly seen with the concave design. Our observations demonstrate that the forces acting on the tibial component vary during active extension, which results in rocking movements. This will influence the migration and the patttern of wear, factors of importance for the clinical longevity of a total knee replacement (TKR). PMID- 11781021 TI - The gastrocnemius muscle is an antagonist of the anterior cruciate ligament. AB - Since the proximal tendon of the gastrocnemius muscle wraps around the posterior aspect of the tibia, its contraction could potentially strain the anterior cruciate ligament (ACL) by pushing the tibia anteriorly. However, the relationship between contraction of the gastrocnemius muscle and ACL strain has not been studied in vivo. The objectives of this study were to evaluate the ACL strain response due to isolated contractions of the gastrocnemius muscle and to determine how these strains are affected by cocontraction with the hamstrings and quadriceps muscles. Six subjects with normal ACLs participated in the study; they underwent spinal anesthesia to ensure that their leg musculature was relaxed. Transcutaneous electrical muscle stimulation (TEMS) was used to induce contractions of the gastrocnemius, quadriceps and hamstrings muscles while the strains in the anteromedial bundle of the ACL were measured using a differential variable reluctance transducer. The ACL strain values produced by contraction of the gastrocnemius muscle were dependent on the magnitude of the ankle torque and knee flexion angle. Strains of 2.8% and 3.5% were produced at 5 degrees and 15 degrees of knee flexion, respectively. The ACL was not strained at 30 degrees and 45 degrees. Changes in ankle angle did not significantly affect these strain values. Co-contraction of the gastrocnemius and quadriceps muscles produced ACL strain values that were greater than those produced by isolated activation of either muscle group when the knee was at 15 degrees and 30 degrees. Co contraction of the gastrocnemius and hamstrings muscles produced strains that were higher than those produced by the isolated contraction of the hamstrings muscles. At 15 degrees and 30 degrees of knee flexion. the co-contraction strain values were less than those produced by stimulation of the gastrocnemius muscle alone. This study verified that the gastrocnemius muscle is an antagonist of the ACL. Since the gastrocnemius is a flexor of the knee, this finding may have important clinical ramifications in ACL rehabilitation since flexor torques are generally thought to be protective of a healing ACL graft. PMID- 11781022 TI - A new device to measure knee laxity during weightbearing and non-weightbearing conditions. AB - The Vermont knee laxity device (VKLD) was developed to evaluate anterior posterior (A-P) displacement of the tibia relative to the femur (A-P laxity) during weightbearing and non-weightbearing conditions. The purposes of this study were to determine the repeatability and reliability of the VKLD measurements of A P laxity and to compare them with two devices currently in clinical use: the KT 1000 knee arthrometer and planar stress radiography. Two independent examiners tested six subjects with no history of knee injury. A-P laxity was measured on three separate days with the KT-1000 and the VKLD. With the VKLD, A-P laxity was measured in the weightbearing and non-weightbearing conditions. In addition, one examiner measured A P laxity in each subject on each day using a planar stress radiography technique. Similar A-P laxity values were obtained with the KT-1000 and the VKLD; however, the planar stress radiography technique measured less A-P laxity compared to the VKLD (9.2+/-2.2 mm versus 13.3+/-2.9 mm, P = 0.0004). None of the three devices showed significant differences in measuring A-P laxity between days. During weightbearing, A-P laxity was reduced by 65-70% compared to the non-weightbearing condition (P = 0.0001). Future investigations will use the VKLD to study subjects that have suffered injury to the anterior and posterior cruciate ligaments. PMID- 11781023 TI - Three-dimensional analysis of shoulder girdle and supraspinatus motion patterns in patients with impingement syndrome. AB - Alterations of the shoulder girdle motion have been suggested to be associated with shoulder disorders. The objective of this study was to perform a three dimensional (3D) motion analysis of the supraspinatus muscle and shoulder girdle in patients with different stages of impingement syndrome. 20 patients with unilateral impingement and 14 normal controls were investigated at 30 degrees, 90 degrees, and 120 degrees of abduction with and without abducting muscle activity. The spatial relationship between the shoulder girdle elements and the supraspinatus was quantified from open MRI data. No significant alterations in glenoid rotation were observed between the patients and asymptomatic volunteers. However, while in the healthy volunteers the values showed a normal distribution (28.5+/-3.6 degrees at 90 degrees abduction with muscle activity), the patients (30.5 degrees+/-9.7 degrees) contained a subset of five individuals with an obvious increase in glenoid rotation angle (>40 degrees) compared with controls (>2.5 standard deviations higher than the mean) and with the healthy contralateral side. These five patients also displayed alterations in the scapulo humeral rhythm and supraspinatus motion, but not in clavicular position. The study shows that only a specific subset of patients with impingement syndrome demonstrates complex changes in shoulder girdle and supraspinatus motion patterns, suggesting that this subset may benefit from an alternative type of treatment. PMID- 11781024 TI - BMP-12 gene transfer augmentation of lacerated tendon repair. AB - Bone morphogenetic protein (BMP) 12 is a recently discovered member of the human BMP family. It is the human homolog of mouse growth/differentiation factor (GDF) 7. Previously we reported that injection of mesenchymal progenitor cells transferred with the BMP-12 gene into the muscles of nude mice induced tendon like tissue formation. In this study, we further investigated the effect of BMP 12 gene transfer on tendon cells. We observed that adenovirus mediated in vitro BMP-12 gene transfer into chicken tendon cells increased type I collagen synthesis. No change in alkaline phosphatase activity was observed following BMP 12 gene transfer. We also determined that BMP-12 gene transfer into a complete tendon laceration chicken model resulted in a two-fold increase of tensile strength and stiffness of repaired tendons, indicating improved tendon healing in vivo. We conclude that BMP-12 gene transfer is a promising procedure for improving the tendon repair process. PMID- 11781025 TI - Neutrophils and macrophages accumulate sequentially following Achilles tendon injury. AB - Structural damage and inflammation occur following tendon injury. The purpose of this study was to determine the time course of inflammatory cell accumulation in two animal models of acute tendinopathy. In the first model, rat Achilles tendons were exposed by blunt dissection, injected with collagenase and sacrificed at 1, 3, 7, 14 and 28 days. In the second model, collagenase was injected percutaneously and rats were sacrificed after 1 and 3 days. Sham animals were sacrificed at 1 and 3 days in both models. Neutrophil and ED1 macrophage populations increased by 46- and 18-fold, respectively, after 1 day in surgically exposed Achilles tendons (EAT) injected with collagenase. Neutrophils dropped by 70% while the concentration of ED1 macrophages remained constant at day 3 post injury. Neutrophils and ED1+ macrophages returned to control values after 7 and 14 days, respectively. ED2+ macrophages showed a tendency to increase at day 28 although no significant difference was observed relative to ambulatory controls. Collagenase injected percutaneously reduced the extent of inflammation compared with operated animals. Thus, injured tendons exhibited a specific sequence of inflammatory cell accumulation which varied in intensity according to the modality used for collagenase injection. PMID- 11781026 TI - The comparison of the wear behavior of four different types of crosslinked acetabular components. PMID- 11781027 TI - Early cell adhesion events differ between osteoporotic and non-osteoporotic osteoblasts. AB - In osteoporosis, the regenerative capacity of bone is compromised, which may involve altered osteoblast (OB) activity. This could be attributed to an inappropriate synthesis and assembly of an extracellular matrix (ECM), altered cell adhesion to the ECM, or be due to inappropriate downstream activation of adhesion-mediated signaling cascades through proteins such as focal adhesion kinase (FAK). The purpose of our study was to compare early adhesion-mediated events using previously described and characterized clinically derived OBs obtained from human patients undergoing major joint arthroplasty for osteoporosis or osteoarthritis. The presence or absence of osteoporosis was established with a radiographic index. Using light microscopy and crystal violet staining, we show that OB cells derived from sites of osteoporosis do not attach and spread as well as non-osteoporotic (OP) OB cells. OP cells initially have a more rounded morphology, and show significantly less (P < 0.001) attachment to serum-coated tissue culture plastic over a 24 h time period. Immunofluorescent labeling after 24 h of attachment showed that OP OB focal adhesions (FAs) and stress fibers were less defined, and that the OP cells were smaller and had a more motile phenotype. When normalized protein lysates were Western blotted for phosphotyrosine (PY) a band corresponding to pp125FAK was identified. FAK tyrosine phosphorylation was evident at 6 h in both the OP and non-OP OBs, but decreased or was absent through 24 h in OP OBs. These results suggest early adhesion-mediated events, such as cell adhesion, attachment, and FAK signaling via PY may be altered in OP OBs. PMID- 11781028 TI - The current status of psychological assessment training in graduate and professional schools. AB - Test-based psychological assessment is threatened by the policies of managed care organizations; however, research has demonstrated that test-based psychological assessment is quite valuable and economically justified when conducted by well trained psychologists. This surfaces the question of the current status of graduate training in test-based psychological assessment. Results of this study indicate that clinical and counseling students currently receive almost equivalent training in test-based assessment. However, in a larger context, results indicate a lack of sound preparation in test-based assessment training for a large proportion of clinical and counseling students. These findings are discussed in terms of their implications for the field and, more specifically, for graduate and internship training. PMID- 11781029 TI - Internal consistency of the object relations and social cognition scales for the Thematic Apperception Test. AB - We examined 8 data sets to determine whether it is possible to attain acceptable levels of internal consistency (coefficient alpha) reliability for the 4 Object Relations and Social Cognition scales (ORSC; Westen, Lohr, Silk, Kerber, & Goodrich, 1989) for the Thematic Apperception Test (TAT; Murray, 1943) when cards are considered as items in a scale. Number of cards used in the data sets ranged from 4 to 10, and the Spearman-Brown prophecy formula was applied to estimate the number of cards that would be required to attain alpha levels of different magnitudes. The two more structural subscales (Complexity of Representations and Understanding of Social Causality) have somewhat higher consistencies than the two more affective ones (Affect Tone and Capacity for Emotional Investment and Moral Standards). The results suggest that the use of 10 to 12 cards provides internal consistencies of alpha > or = .70 across each of the 4 ORSC scales. PMID- 11781030 TI - The effectiveness of MMPI-A items in discriminating between normative and clinical samples. AB - The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992) was released in 1992 and has rapidly become the most widely used objective personality assessment instrument with adolescents. Although the MMPI-A reduced or eliminated several problems associated with the use of the original MMPI (Hathaway & McKinley, 1943) with adolescents, the MMPI-A does produce a high frequency of within normal limits basic scale profiles for individuals with substantial psychopathology including adolescents in inpatient psychiatric settings. To better understand the reasons for this phenomenon, we compared the item endorsement frequencies for the MMPI-A normative sample with results from two adolescent clinical samples, and these results were contrasted to the item endorsement frequencies for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) normative sample and a clinical sample of adult psychiatric inpatients. Results showed that the MMPI-A contains a substantial number of items that do not show a significant difference in item endorsement frequency between normative and clinical samples. Furthermore, MMPI-A basic and content scales generally show a much lower percentage of effective items than do the corresponding scales for the MMPI-2. We discuss the findings in relation to the frequent occurrence of low range MMPI-A profiles in clinical samples and the potential usefulness of these results in future efforts to develop viable short forms for the MMPI-A. PMID- 11781031 TI - Development of a spanish version of the Schwartz Outcome Scale-10: a brief mental health outcome measure. AB - The lack of culturally appropriate psychometric instruments for the assessment of cognitive and emotional functioning in minority populations has been a concern often discussed in the assessment literature. With the increased focus on the measurement of outcome in mental health treatment, the lack of appropriate instruments for minorities has become readily apparent in this venue as well. We report on the Spanish translation of a brief and reliable measure of psychological health and well-being that has been shown to be sensitive to treatment outcomes. The original and Spanish translated versions of this measure are highly correlated, providing clinicians and organizations with a instrument that can be used for assessment of psychological well-being and treatment outcomes with Hispanic patients. PMID- 11781032 TI - Assessment of disordered thinking in children and adolescents: the rorschach perceptual-thinking index. AB - The new Rorschach Perceptual-Thinking Index (PTI; Exner, 2000a, 2000b) was designed to assess thought disorders more accurately than the Schizophrenia Index (SCZI; Exner, 1993). Using a sample of child and adolescent inpatients, we examined the relation of Rorschach variables (PTI, SCZI, M-, and X- %) to thought disorder indexes on a behavior rating scale (Behavior Assessment System for Children; Reynolds & Kamphaus, 1992) and a self-report measure (Personality Inventory for Youth; Lachar & Gruber, 1995). Results indicate that, when used in a categorical manner, the PTI differentiated between those patients with and without elevated thought disorder scores on the other measures. Of all Rorschach variables, M- was most related to the other measures, indicating that this variable may be a particularly robust indicator of thought disorder among children and adolescents. PMID- 11781033 TI - Scoring accuracy using the comprehensive system for the Rorschach. AB - The Comprehensive System (CS; Exner, 1974, 1978) for scoring Rorschach responses is the most widely taught and most widely accepted system in use today. The complexity and labor- intensive nature of the CS makes the issue of scoring accuracy a central concern. Twenty-one graduate psychology students and 12 professionals scored 20 Rorschach responses drawn from normal and clinical protocols. In general. accuracy scores for both students and professionals were below acceptable levels. Accuracy scores were clearly better for the code categories of Location, DQ, Pairs, Popular, and Z than for Determinants, FQ, Content, and Special Scores. Responses from clinical protocols were subject to more error. The results suggest that high levels of scoring errors may exist in the field use of the CS. Training standards may need to be devised to insure scoring competence. PMID- 11781034 TI - Development and initial validation of the Self-harm Behavior Questionnaire. AB - Evaluation of suicide-related behaviors and thoughts about suicide with a newly developed self-report instrument is described. The Self-Harm Behavior Questionnaire (SHBQ; Gutierrez, 1998) generates detailed clinical information from an easy to administer and score self-report form. A sample of 342 participants were drawn from university undergraduate students enrolled in various psychology courses. Participants were then divided into a severe suicidal ideation group (n = 20) and a nonsuicidal control group (n = 20) to conduct subgroup and criterion-related validity analyses. Preliminary analyses indicate this new questionnaire is both valid and reliable when used with young adults drawn from a nonclinical population. The questionnaire should be of use to both clinicians and researchers due to the flexibility of the data generated. PMID- 11781035 TI - Clinical utility of the Rorschach with African Americans. AB - In this study we sought to identify Rorschach differences between African Americans and White Americans and to understand these differences within a social and cultural framework. Data from the Exner (1993) Comprehensive System normative sample (N = 700) was used to form a group of 44 African Americans and 44 White Americans matched for age, sex, education, and socioeconomic status. Twenty-three Rorschach variables were chosen a priori and group differences were analyzed. The only clinically significant difference found was that African Americans offered significantly less cooperative movement. This lower frequency of cooperative movement may suggest African Americans do not anticipate cooperative interactions with others as a routine event. This may reflect a shared feeling among African Americans that most members of our society are less likely to be sensitive to or responsive to their needs relative to others. However, the study demonstrates a striking similarity between the groups, supporting the clinical use of the Rorschach with African Americans. PMID- 11781036 TI - Use of the MMPI-A to detect substance abuse in a juvenile correctional setting. AB - In this study, we examined the ability of the MMPI-A (Butcher et al., 1992) to detect substance abuse problems in a juvenile correctional setting. Specifically, we evaluated the Alcohol/Drug Problem Acknowledgment scale (ACK; Weed, Butcher, & Williams, 1994), the Alcohol/Drug Problem Proneness scale (PRO; Weed et al., 1994), and the MacAndrew Alcoholism Scale-Revised (MAC-R; Butcher et al., 1992) in the prediction of substance abuse. In addition, the incremental validity of ACK in comparison to PRO was evaluated, as was the incremental validity of PRO in comparison to ACK. The sample consisted of 123 boys and girls from ajuvenile correctional facility in Northeastern Ohio. Results indicate that ACK and PRO, but not MAC-R, were related to interviewer ratings of substance abuse. Results point to the superiority of ACK over PRO in substance abuse identification. PMID- 11781037 TI - Adherence to substance abuse treatment: clinical utility of two MMPI-2 scales. AB - In this study, we examined the ability of the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Addiction Acknowledgment scale (AAS; Weed, Butcher, McKenna, & Ben-Porath, 1992) and Negative Treatment Indicators scale (TRT; Butcher, Graham, Williams, & Ben-Porath, 1990) to predict adherence to and outcomes from substance abuse treatment. There was no evidence that the AAS was related to treatment adherence or outcome in our sample. However, results did reveal a significant positive relation between scores on the TRT scale and readmission to the hospital. Further analyses identified an optimal score for use in similar clinical populations and settings, and characteristics of high and low scorers. Compared to low scorers, high TRT scorers were more likely to not return for treatment after an initial screening interview. If they did return for treatment, high TRT scorers were more likely to experience fewer treatment days and to be rated as having lower motivation, poorer participation, and poorer comprehension of program materials. These findings provide promising initial evidence of the utility of the TRT scale for identifying patients who may be at a high risk for unsuccessful substance abuse treatment. PMID- 11781038 TI - A critical review of the validity of ego development theory and its measurement. AB - Loevinger's (1976) theory of ego development represents an important and original approach to understanding personality development. More than 20 years have elapsed since the last substantial critical review of the validity of the theory and its measurement (Loevinger, 1979). Our article provides an updated critical review of the theory by reviewing the considerable body of research that has accumulated over the past 20 years. This review addresses the construct, predictive, and discriminant validity of ego development theory and the Washington University Sentence Completion Test (WUSCT; Loevinger & Wessler, 1970; Loevinger, Wessler, & Redmore, 1970) as its measurement. We conclude that there is substantial empirical support for the conceptual soundness of ego development theory and the WUSCT. PMID- 11781039 TI - Psychometric properties of the beck depression inventory-II with university students in Bahrain. AB - The Arabic version of the Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) was administered to 200 students enrolled at the University of Bahrain. Using exploratory and confirmatory factor analytic techniques, I obtained reasonable validity and reliability data for the BDI-II. Three oblique factors provided the most parsimonious and meaningful solution for students' responses. Findings of this study generally provide strong support for the psychometric soundness of the BDI-II as a measure of depression in college student populations even in Arabic culture, which differs dramatically from Western culture in both values and taboos. PMID- 11781040 TI - Hearing in the elderly: a population study. AB - An epidemiological study comparing speech audiometry with self-assessed hearing disability and an analysis of other factors influencing the quality of life was conducted. In the Veneto region (Italy), a representative sample of 2700 independently living individuals of 65 years of age and older was selected for the study. All participants were administered a comprehensive questionnaire and a brief examination at their home, including a general physical examination, speech audiometry, Sanders' Speech Disability test, part I and III, Mini Mental State Examination, CES-D scale for depression, visual acuity, self-reported diseases and physical function. Auditory function was worst in the older individuals: auditory performance was within acceptable limits up to the 75-79 age group, while it rapidly deteriorates in the older groups. This trend is consistent with self-reported auditory disability (Sanders' test). A detailed analysis of the type of errors made in the speech audiometry was conducted for each subject. Speech audiometry is a good indicator of real hearing difficulties faced by the elderly, and it might be preferred to pure-tone audiometry, since hearing deficits with age are not always limited to an increased detection threshold, but include other aspects of hearing such as distortion of sounds, comprehension of speech and noise discrimination. PMID- 11781041 TI - Determination and classification of the problems experienced by hearing-impaired elderly people. AB - The aim of this study was to determine whether participation restrictions and contextual factors could be elicited in an elderly hearing-impaired population using an open-ended questionnaire. The study also tested the value of the World Health Organization's ICF in the classification of the problems experienced by the elderly hearing-impaired. To this end, we administered the 'Life Effects Questionnaire', in which the subjects were asked to list the effects of their hearing loss on their lives. With this approach, significantly more participation restrictions, environmental factors and personal factors were elicited than with a traditional approach. ICF proved useful in classifying these, but the Activity and Participation Scales had a major weakness in terms of non-communication related hearing problems. Furthermore, a high proportion of the responses came into the personal factors, for which a formal classification does not exist within ICF. This highlights a significant need in that classification. PMID- 11781042 TI - Cochlear function and speech recognition in the elderly. AB - The aim of the current study was to evaluate the performance of elderly subjects in advanced tests that assess primary cochlear functions (temporal summation, frequency selectivity, cochlear mechanics) and relate them to speech recognition scores. The results show that measures of primary cochlear function in elderly subjects are worse than in young adults, suggesting that receptor failure primarily involved presbyacusis'. Moreover, the data suggest that significant changes in the conductive structures within the inner ear could be involved in age-related hearing loss. Peripheral function deterioration seems to be highly relevant for speech recognition; in fact, it was found that the elderly with the poorest speech recognition scores also had the worst frequency selectivity. PMID- 11781043 TI - Effect of ageing on otoacoustic emissions and efferent suppression in humans. AB - Transiently evoked otoacoustic emissions (TEOAEs) without and with contralateral acoustical stimulation, were recorded on 52 subjects ranging from 20 to 78 years. Subject selection was based on the hearing levels from 0.5 to 4 kHz being better than 25 dB HL, normal tympanograms and stapedial reflexes, presence of TEOAEs in at least one ear and no history of otological disease, noise exposure, ototoxic drugs, metabolic disease associated with hearing loss or a family history of hearing loss. The ear with better audiological thresholds was selected as the test ear. If there was no difference between the ears, the ear with stronger TEOAEs was selected. Subjects were divided into five age groups: 20-34 years (n=12, mean age 23.7), 35-44 (n=11, mean age 39.7), 45-54 (n=8, mean age 48.1), 55-64 (n=10, mean age 60), 65-78 (n=11, mean age 71). TEOAEs were never absent in the first two groups, but they were absent in two ears in the 45-54 group, and in one ear of the 55-64 and 65-78 groups. Mean TEOAE amplitude decreased with age, but the differences between the five groups were not significant. Contralateral white noise suppressed emission amplitude, but the amount of suppression was not significantly different between the five groups. A linear regression analysis showed a significant correlation between age and hearing levels, and a negative correlation between age and TEOAE amplitude. In addition, a significant negative correlation between hearing threshold and TEOAE amplitude was evident. No effect of age on the amplitude of the efferent suppression was found. PMID- 11781044 TI - Anatomical, metabolic and genetic aspects of age-related hearing loss in mice. AB - Because of their short lifespan and genetic homogeneity, mice can provide valuable insights into the biological basis of age-related hearing loss. In C57BL/6 mice, hair cell loss begins around 1-2 months of age and progresses rapidly along a base-to-apex gradient, whereas CBA mice show relatively little hair cell loss until late in life. This anatomical difference is reflected in dehydrogenase histochemistry, an indirect measure of aerobic energy metabolism. A small, but significant, decrease in hair cell dehydrogenase staining occurred in CBA mice between 1.5 and 18 months of age. Significantly, dehydrogenase levels in 1.5-month C57 mice were substantially lower than in CBA mice of any age. Thus, deficits in aerobic energy metabolism presage degeneration of the hair cells. The superoxide radical, O2*-, a normal byproduct of cellular metabolism, is potentially toxic and can cause cellular damage if it is not inactivated by superoxide dismutases. Cytosolic copper/zinc superoxide dismutase (SOD1) is highly expressed in the cochlea. Knockout mutant mice with a single (HET) or double deletion (KO) of the Sod1 gene coding for SOD1 showed greater age-related losses than wild-type (WT) mice. KO mice had the worst hearing, WT the best, and HETs were intermediate. KOs exhibited considerably greater hair cell loss than WT mice; however, losses in KOs were only slightly greater than in HETs. KO mice showed significantly greater loss of spiral ganglion cells and nerve fibers than WT mice. These results indicate that SOD1 and O2*- play important roles in age related hearing loss. Intervention strategies targeting O2*- may reduce age related hearing loss. PMID- 11781045 TI - Age-related histopathological changes of the stria vascularis: an experimental model. AB - The stria vascularis (SV) of 3-, 8- and 18-month-old C57 mice was examined with a fluorescence microscope in order to evaluate the capillary density and vessel diameter. The capillary density was significantly reduced in 18-month-old mice compared to 3-month-old (P<0.001) and to 8-month-old (P<0.001) mice. The difference between 3- and 18-month-old mice was significant for the basal, middle and apical cochlear turns, while the difference between 8- and 18-month-old mice was significant only for the middle and basal turns. Vessel diameter within the whole SV was significantly reduced in all turns in 18-month-old mice (P<0.01) versus 3-month-old animals, while vessel diameter was reduced only in the basal turn in 8-month-old versus 3-month-old mice. The results suggest that previously described histopathological changes in the organ of Corti of C57 mice may be related to modifications of strial capillaries. PMID- 11781046 TI - Apoptosis in the OC-k3 immortalized cell line treated with different agents. AB - The aim of this study is to outline the mechanisms leading cochlear cells to die. We utilized an immortalized cell line (OC-k3 cells) derived from the organ of Corti of transgenic mice in order to perform in-depth biochemical studies with no limitations on sample size and number. We probed these cells with cisplatin and gentamicin, two drugs which display in vivo undesired ototoxic side-effects. We investigated cell viability, reactive oxygen species (ROS) production and glutathione (GSH) levels and tested the effects of different concentrations of cisplatin and gentamicin from 0 to 48 h. Results show that cells undergo a dose- and treatment-time-dependent apoptosis characterized by nuclear fragmentation, integrity of the cell membrane and mitochondria, and absence of DNA endonuclease activity. During the early part of treatment, ROS production increases and intracellular GSH decreases, probably due to the activation of protein kinase C alpha. Use of antioxidants such as N-acetylcysteine, GSH and vitamin C rescues cells from apoptosis almost completely. Overall, these data indicate that ROS generation might play a central role in inducing inner ear cell apoptosis and may have an additive role in the ageing process. PMID- 11781047 TI - Lexical representation and processing of morphologically complex words: evidence from the reading performance of an Italian agrammatic patient. AB - The study of patients with acquired language disorders has provided crucial evidence for contemporary theories on mental lexical representation. This is particularly true for the representation of morphologically complex words. In this paper we analyzed the performance of a patient (M.B.) affected by agrammatism and dyslexia. M.B. was required to read aloud simple and morphologically complex words. The patient's pattern of errors was interpreted as the result of a predominant use of the lexical routine (phonological dyslexia). Three reading tasks were developed which allowed us to test M.B.'s ability to read morphologically complex words (reading of regular and irregular plurals; reading of high- and low-frequency singular and plural nouns; reading of evaluative suffixes). Errors were determined by frequency effect rather than by type of suffix (i.e., inflectional or derivational). High-frequency morphologically complex items seemed to meet stored representations, thus avoiding the parsing procedures that are required for less frequent items. These results are in keeping with dual route models of lexical representation of morphologically complex words. PMID- 11781048 TI - Does global context modulate cerebral asymmetries? A review and new evidence on word imageability effects. AB - In this article we examine whether the distribution of function across the right and left cerebral hemispheres for lexical processing is influenced by the global context within which words are presented. A review of previously published studies indicates that the ubiquitous right visual field (RVF)/left hemisphere advantage for word recognition may be reduced or eliminated for nouns, content words, or high image words, but only when such items are presented along with verbs, function words, or low image words. However, paradoxically, when the former items are presented in more homogeneous contexts, the RVF advantage is uniformly observed. We propose that the processing efficiency of a hemisphere for a given stimulus depends on that item's relation to the other stimuli provided, that is, the global context. This was examined in a visual half-field experiment that varied whether high and low image nouns were presented in homogeneous (blocked lists) or heterogeneous (mixed lists) contexts. An unvarying RVF advantage was observed for high image words in homogeneous contexts, but this advantage was eliminated when the same items were presented in heterogeneous contexts. We suggest that stimulus heterogeneity maximizes reliance on differing, but complementary, computational biases across hemispheres. Hence, the extent to which the left and right hemispheres are recruited for the recognition of individual word types can vary dynamically with variation in the stimulus environment. PMID- 11781049 TI - Spoken language outcomes after hemispherectomy: factoring in etiology. AB - We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology. PMID- 11781050 TI - Word length and vowel duration in apraxia of speech: the use of relative measures. AB - Previous research has established that the duration of stressed word stem vowels is shorter in polysyllabic words than in monosyllabic words for normal speakers and for speakers with aphasia and apraxia of speech (AOS). However, the results are inconsistent across studies with regard to the magnitude and pattern of the duration reduction for apraxic speakers. We hypothesized that this inconsistency may be explained based on different relative measures of duration reduction. A speech sample was obtained from 10 aphasic speakers with AOS, 10 aphasic speakers without AOS, and 10 normal controls. As predicted, the use of two different relative measures resulted in different vowel reduction patterns, both of which were consistent with previous reports. The results further indicate that the production of polysyllabic words is particularly taxing in AOS and is associated with a substantial reduction of speaking rate compared to other aphasic and normal speakers. PMID- 11781051 TI - The effects of scrambling on Spanish and Korean agrammatic interpretation: why linear models fail and structural models survive. AB - Several models of comprehension deficits in agrammatic aphasia rely heavily on linear considerations in the assignment of thematic roles to structural positions (e.g., the Trace-Deletion Hypothesis, the Mapping Hypothesis, and the Argument Linking Hypothesis). These accounts predict that constructions in languages with rules that affect syntactic structure but preserve relative linear order should be unimpaired. Other models [e.g., the Double-Dependency Hypothesis, (DDH)] do not resort to linearity but are purely structural in conception and therefore should be immune to word-order effects. We tested linear and nonlinear accounts with scrambling structures in Korean and topicalization structures in Spanish. The results are very clear. The (nonlinear) DDH is entirely compatible with the evidence, but the linear accounts are not. PMID- 11781052 TI - Acquired crossed aphasia in dextral children revisited. AB - In contrast to the estimated low incidence of crossed aphasia in dextral adults (among 1%), crossed aphasia in children has been considered a common finding for almost a century. However, reviewing the literature on crossed aphasia in dextrals (CAD) and its related topics from 1975 onward, we encountered only 5 children in a corpus of 180 cases (2.7%). Critical analysis rendered three of the reported cases ambiguous and hence not suitable to draw potentially relevant conclusions. In this review, the neurobehavioral manifestations of the two representative childhood CAD cases are analyzed and compared with adult CAD and acquired childhood aphasia (ACA). In the light of our findings, which support the position of innate cerebral specialization for language, the long-standing controversy as to whether lateralized hemispheric specialization for language is innate or develops progressively during maturation is briefly discussed. PMID- 11781053 TI - Mapping from sound to meaning: reduced lexical activation in Broca's aphasics. AB - Recent studies of lexical access in Broca's aphasics suggest that lexical activation levels are reduced in these patients. The present study compared the performance of Broca's aphasics with that of normal subjects in an auditory semantic priming paradigm. Lexical decision times were measured in response to word targets preceded by an intact semantically related prime word ("cat"-"dog"), by a related prime in which one segment was acoustically altered to produce a poorer phonetic exemplar ("c*at"-"dog"), and by a semantically unrelated prime ("ring"-"dog"). The effects of the locus of the acoustic distortion within the prime word (initial or final position) and the presence of potential lexical competitors ("cat" --> /gaet/versus "coat" --> "goat") were examined. In normal subjects, the acoustic manipulations produce a small, short-lived reduction in semantic facilitation irrespective of the position of the distortion in the prime word or the presence of a voiced lexical competitor. In contrast, Broca's aphasics showed a large and lasting reduction in priming in response to word initial acoustic distortions, but only a weak effect of word-final distortions on priming. In both phonetic positions, the effect of distortion was greater for prime words with a lexical competitor. These findings are compatible with the claim that Broca's aphasics have reduced lexical activation levels, which may result in a disruption of the bottom-up access of words on the basis of acoustic input as well as increased vulnerability to competition between acoustically similar lexical items. PMID- 11781054 TI - Complementarity of linguistic and prosodic processes in the intact brain. AB - Despite considerable speculation in the research literature regarding the complementarity of functional lateralization of prosodic and linguistic processes in the normal intact brain, few studies have directly addressed this issue. In the present study, behavioral laterality indices of emotional prosodic and traditional linguistic speech functions were obtained for a sample of healthy young adults, using the dichotic listening method. After screening for adequate emotional prosody and linguistic recognition abilities, participants completed the Fused Rhymed Words Test (FRWT; Wexler & Halwes, 1983) and the Dichotic Emotion Recognition Test (DERT; McNeely & Netley, 1998). Examination of the difference in ear asymmetries for these measures within individuals revealed a complementary pattern in 78% of the sample. However, the correlation between laterality quotients for the FRWT and DERT was near zero, supporting Bryden's model of "statistical" complementarity (e.g., Bryden, 1990). PMID- 11781055 TI - Production of stress retraction by left- and right-hemisphere-damaged patients. AB - An acoustic-perceptual investigation of a phonological phenomenon in which stress is retracted in double-stressed words (e.g., thirTEEN vs THIRteen MEN) was undertaken to identify the locus of functional impairments in speech prosody. Subjects included left-hemisphere-damaged (LHD) and right-hemisphere-damaged (RHD) patients and nonneurological controls. They were instructed to read sentences containing double-stressed target words in the presence of a clause boundary or its absence. Whereas all three groups of subjects were capable of manipulating the acoustic parameters that signal a shift in stress, there were some differences between the performance of the patient groups and that of the normal controls. Further, stress production deficits were more severe in LHD aphasic patients than in RHD patients. LHD speakers exhibited deficits in the control of both temporal and F0 cues. Their F0 disturbance appears to be secondary to a primary deficit in temporal control at the phase or sentence level, as an increased number of continuation rises found for the LHD patients seemed to arise from lengthy pauses within sentences. Findings are highlighted to address the nature of breakdown in speech prosody and the competing views of prosodic lateralization. PMID- 11781056 TI - Reperfusion of specific brain regions by raising blood pressure restores selective language functions in subacute stroke. AB - We report a series of six single subject studies examining the effects of pharmacological blood pressure elevation on regional brain perfusion and language function. Previous reports indicate that hypoperfusion of specific brain regions, as delineated by magnetic resonance perfusion weighted imaging (PWI), is associated with disruption of selective lexical functions. On this basis, we hypothesized that reperfusion of the same regions, in the absence of infarct in that region, would restore the associated lexical function. We present five patients with impaired lexical-semantics associated with poor perfusion, but not infarction, of Brodmann's area 22 (BA 22), and one patient with impaired lexical semantics and a superimposed deficit in retrieving the phonological representations of words, associated with poor perfusion Brodmann's area 37 (BA 37) as well as BA 22. Each patient was treated with induced blood pressure elevation to increase perfusion of the ischemic and dysfunctional tissue. Daily testing of naming and comprehension, with stimulus sets matched for frequency, familiarity, and length, showed improved lexical-semantics in the patients who showed reperfusion of BA 22 and improved oral naming (but not lexical-semantics) in the patient who showed reperfusion of BA 37. These cases illustrate that loss of function with hypoperfusion of a circumscribed area of the brain, and recovery of the same function with improved perfusion of that brain region, can reveal brain/language relationships prior to reorganization after brain injury. PMID- 11781057 TI - Phonology: a review and proposals from a connectionist perspective. AB - A parallel distributed processing (PDP) model of phonological processing is developed, including components to support repetition, auditory processing, comprehension, and language production. From the performance of the PDP reading model of Plaut, McClelland, Seidenberg, and Patterson (1996), it is inferred that the acoustic-articulatory motor pattern associator that supports repetition provides the basis for phonological sequence knowledge. From the observation that many patients make phonemic paraphasic errors in language production, as in repetition, it is argued that there must be a direct link between distributed concept representations (lexical semantic knowledge) and this network representation of sequence knowledge. In this way, both lexical semantic and phonotactic constraints are brought to bear on language production. The literature on phonological function in normal subjects (slip-of-the-tongue corpora) and in patients with aphasia is critically reviewed from this perspective. The relationship between acoustic and articulatory motor representations in the process of phonetic perception is considered. Repetition and reproduction conduction aphasia are reviewed in detail and extended consideration is given to the representation of auditory verbal short-term memory in the model. Finally, the PDP model is reconciled with information processing models of phonological processing, including that of Lichtheim, and with current knowledge of the anatomic localization of phonological processing. Although no simulations of the model were run, a number of simulation studies are proposed. PMID- 11781058 TI - The lateralized linguistic cerebellum: a review and a new hypothesis. AB - During the past 2 decades the collaboration across disciplines and the methodologic and conceptual advances of contemporary neuroscience have brought about a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Growing insights in the neuroanatomy of the cerebellum and its interconnections, evidence from functional neuroimaging and neurophysiological research, and advancements in clinical and experimental neuropsychology have established the view that the cerebellum participates in a much wider range of functions than conventionally accepted. This increase of insight has brought to the fore that the cerebellum modulates cognitive functioning of at least those parts of the brain to which it is reciprocally connected. This article reviews the recently acknowledged role of the cerebellum in cognition and addresses in more detail experimental and clinical data disclosing the modulatory role of the cerebellum in various non motor language processes such as lexical retrieval, syntax, and language dynamics. In agreement with the findings indicating a topographical organization of the cerebellar structures involved in language pathology we advance the concept of a "lateralized linguistic cerebellum." In our view crossed cerebral diaschisis processes, reflecting a functional depression of supratentorial language areas due to reduced input via cerebellocortical pathways, might represent the relevant pathomechanism for linguistic deficits associated with cerebellar pathology. PMID- 11781060 TI - Progressive encephalopathy in primary immunodeficiency disease. PMID- 11781061 TI - Insulin-specific tolerance in diabetes. AB - At present it is possible to predict the development of type 1A diabetes (immune mediated diabetes) in man and prevent the disorder in animals. Studies of immunity to insulin play a prominent role in both disease prediction and disease prevention. For both man and the NOD mouse, insulin autoantibodies usually precede the development of diabetes and can be utilized to assist in disease prediction. T cells clones recognizing insulin, both CD4 and CD8, can transfer disease to young mice or immunodeficient animals. Specific insulin peptides reacting with these clones have been identified, their crystal structure when bound to a human "diabetogenic" MHC allele has been determined, and specific peptides can be used either to induce or to prevent disease. Clinical trials of both insulin and an altered peptide ligand of insulin to prevent islet beta-cell destruction are underway. Insulin is one of a number of islet autoantigens, but it is likely that immune responses to insulin will be central to both pathogenesis and immunologic protection. PMID- 11781062 TI - Systemic and mucosal immune responses in mice after rectal and vaginal immunization with HIV-DNA vaccine. AB - We examined the feasibility of inducing local and systemic human immunodeficiency virus (HIV)-specific immune responses by rectal and vaginal application of an HIV DNA vaccine. Mice were immunized with an HIV-DNA vaccine preparation via a rectal or vaginal route. After several applications, HIV-specific antibodies were detected in sera, fecal extract solutions, and vaginal washes, and these antibodies were potent in inhibiting the syncytium formation of a CD4-positive human T cell line by a cell line capable of inducing HIV-1 infection. Spleen cells from rectally and vaginally immunized mice showed antigen-mediated IFN gamma-inducing activity. In addition, with rectal immunization, mononuclear cells from both the spleen and the regional lymph nodes of the rectal region were found to be potent at inducing a cytotoxic T lymphocyte response. These humoral and cell-mediated immune responses were enhanced by augmenting the vaccine with granulocyte-macrophage colony-stimulating factor-expressing plasmids or IL-12 expressing plasmid. Our results demonstrated that both rectal and vaginal immunization could induce systemic and mucosal immunity and that these responses were enhanced by the addition of the above cytokine-expressing plasmids. PMID- 11781063 TI - Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment. AB - We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended. PMID- 11781064 TI - 561del4 defines a novel small deletion hotspot in the interferon-gamma receptor 1 chain. AB - Patients with a dominant small deletion (818del4, hotspot) in the interferon gamma receptor 1 (IFNGR1) gene (6q23-q24) and increased susceptibility to mycobacterial infections have been recently reported. We describe a female patient homozygous for a 4-bp deletion in exon 5 of IFNGR1 (561del4) who developed postvaccinal disseminated Bacille Calmette-Guerin infection. She was born to unrelated Argentinean parents, each of whom was heterozygous for this mutation. 561del4 has been previously described as a maternally inherited mutation in a compound heterozygous German patient. By single nucleotide polymorphism analysis of the areas surrounding the deletion, we showed the independent inheritance of 561del4 in three heterozygous carriers. Polypurine runs and "direct repeats," previously shown to be associated with areas of recurrent small deletions, were found in the flanking region of 561del4. The independent inheritance of three identical mutational events defines 561del4 as a new hotspot in the IFNGR1 gene. PMID- 11781065 TI - Chlamydia trachomatis infection inhibits airway eosinophilic inflammation induced by ragweed. AB - While much progress has been achieved in controlling infectious diseases, there is a startling increase in the prevalence of allergic disorders in developed countries. Previous studies using experimental murine models of asthma have demonstrated that mycobacterial infections are capable of suppressing asthma-like reactions induced by ovalbumin (OVA). Using a different intracellular bacterium, Chlamydia trachomatis mouse pneumonitis (MoPn), we examined the effect of infection on the development of allergic responses to a common natural airborne allergen, ragweed (RW). The data showed that airway eosinophilia induced by ragweed sensitization/challenge was significantly reduced in MoPn-infected mice. MoPn-infected mice also exhibited significantly lower levels of allergen-driven Th2 cytokine production, namely IL-4, IL-5, IL-10, and IL-13, following ragweed exposure in comparison with those treated with ragweed only. Additionally, the production of eotaxin, a C-C chemokine for eosinophil chemoattraction following RW exposure, was significantly reduced in the lungs of MoPn-infected mice. However, MoPn infection did not reduce the levels of RW-specific IgE and IgG1 production in the sera, nor did it diminish the level of total serum IgE. These data provide evidence that the suppression of the allergic airway inflammation induced by a common environmental allergen is attainable through intracellular bacterial infection. PMID- 11781066 TI - Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck. AB - In cancer, regional lymph node (LN) cells are one of the first components of the immune system to have contact with tumor cells or their products. Therefore, the phenotype and functional properties of hematopoietic cells present within the tumor-draining LN are important to understanding their role in the control of malignant cells. Based on the locoregional metastatic behavior of squamous cell carcinoma of the head and neck (SCCH&N) region, we analyzed tumor-draining lymph nodes from SCCH&N patients to obtain insights into regional tumor immunity. Using a three-color fluorescent labeling technique, surface antigen expression was visualized in mononuclear cells of lymph nodes that were obtained from head and neck cancer patients and compared to mononuclear cells of normal lymph nodes. Cell cycle analyses were performed using propidium iodide. Proliferation after phytohemagglutinin stimulation was measured by a sodium tetrazolium-based assay. LN histology was correlated with flow cytometric findings. Regional lymph nodes of head and neck cancer patients undergo morphologic and functional changes. Flow cytometry revealed a decrease in CD8(+) T cells and in some lymph nodes the presence of second or third populations of larger cells with distinct size and granularity that expressed both T (gammadelta/alphabeta) and different natural killer cell markers. Moreover, cell cycle analyses and proliferation assays showed a diminished response to mitogenic stimuli. These changes were found in both metastatic and hyperplastic lymph nodes from head and neck cancer patients; however, no alterations were found in control lymph nodes or peripheral blood mononuclear cells from noncancer patients. The immune alterations detected in lymphocytes present within the draining lymph nodes of head and neck cancer patients may improve our understanding of how tumor cells escape host immunosurveillance. However, this dysfunction in local draining lymph nodes may not be detected systemically. PMID- 11781067 TI - Animal models of human disease: experimental autoimmune gastritis--a model for autoimmune gastritis and pernicious anemia. AB - Human autoimmune gastritis is an organ-specific autoimmune disease of the stomach. It is characterized by the development of disease-specific autoantibodies and a pathology that specifically targets specialized cells within the gastric environment. The autoantigens associated with this disease have been defined as the gastric H+/K+ ATPase and intrinsic factor. The development of experimental disease models has been pivotal in our contemporary understanding of autoimmunity. Here we review mouse models of autoimmune gastritis and their relevance to human autoimmune gastritis associated with pernicious anemia. We appraise some historical as well as recent studies of experimental autoimmune gastritis (EAG), highlighting key findings that have formed the basis of our current understanding of the etiology and mechanism(s) associated with autoimmune gastritis. A precise understanding of the pathogenesis of autoimmune gastritis will permit the design of innovative and rational therapeutic strategies to prevent, arrest, ameliorate or reverse the disease. PMID- 11781068 TI - Intravenous immunoglobulin therapy in patients with multiple mucosal involvement in mucous membrane pemphigoid. AB - Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is an autoimmune mucocutaneous, blistering disease which can lead to blindness and/or death from sudden asphyxiation, secondary to a scarring process. Conventional therapy for the treatment of MMP consists of high-dose systemic corticosteroids and/or immunosuppressive agents. Some patients do not respond to these treatments and develop multiple serious side effects, which can be potentially fatal. In such patients, alternative treatment modalities are needed. This study presents the use of intravenous immunoglobulin (IVIg) therapy in 15 patients with severe MMP whose disease was nonresponsive to the prolonged use of high-dose systemic corticosteroids and immunosuppressive agents and who developed multiple side effects to them. All 15 patients received an IVIg dose of 1-2 g/kg/cycle. The following objective parameters were used to assess the clinical outcome pre- and post-IVIg therapy: number of side effects, frequencies of recurrences and relapses, duration and total dosage of prednisone therapy, and the quality of life. The differences in these variables between the pre- and post IVIg data were statistically analyzed using the SAS UNIVARIATE software running the two-sided Wilcoxon signed-rank and sign tests. A statistically significant difference was observed between pre- and post-IVIg therapy data when comparing the aforementioned variables. All 15 patients had an effective clinical response, were able to discontinue previous systemic therapies, and eventually achieved a prolonged clinical remission. IVIg improved the quality of life in all 15 patients and demonstrated a steroid-sparing effect. No serious side effects were observed. IVIg therapy is a safe and effective alternative modality in the treatment of patients with nonresponsive and progressive MMP and can induce a sustained clinical remission. PMID- 11781069 TI - Decreased lamina propria effector cell responsiveness to interleukin-10 in ileal Crohn's disease. AB - We investigated whether a lack of IL-10 production or responsiveness could be involved in Crohn's disease pathogenesis. Lamina propria mononuclear cells, isolated from the ilea of Crohn's disease patients (n = 16) and controls (n = 13), were activated with anti-CD3 mAb in the presence of CD80 transfectants or LPS +/- IFN-gamma. No evidence for deficient IL-10 production by either T cells or macrophages in Crohn's disease was found. However, the efficacy of rhIL-10 to down-regulate IFN-gamma and especially TNF production in cell cultures from the involved tissues of Crohn's disease patients was poor, and the use of an anti-IL 10R mAb even provided evidence for proinflammatory effects of IL-10. This lack of IL-10 effect possibly results from IL-12 activity. We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohn's disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohn's disease patients. PMID- 11781070 TI - Animal model of sclerotic skin. V: Increased expression of alpha-smooth muscle actin in fibroblastic cells in bleomycin-induced scleroderma. AB - Scleroderma is a connective tissue disorder with unknown etiology. Myofibroblasts appear during fibrotic processes such as scleroderma, hypertrophic scarring, and wound healing. We previously established a mouse model for scleroderma by local injections of bleomycin. To determine the phenotype of the fibroblasts in sclerotic skin after bleomycin treatment, we examined the expression of alpha smooth muscle actin (alpha-SMA), a marker for myofibroblasts, in lesional skin as well as in fibrous lung in this model. Dermal sclerosis was induced by daily local injections of bleomycin (100 microg/ml) for 3 weeks in C3H mice. Immunohistochemical examination showed that alpha-SMA-reactive cells were detectable on fibroblastic cells in bleomycin-injected skin at 1 week. There was a significant increase in the immunoreactive fibroblastic cells for alpha-SMA in lesional skin in parallel with the induction of dermal sclerosis. After 3 weeks' treatment with bleomycin, the number of alpha-SMA-reactive fibroblasts showed an 11-fold increase compared with that in control PBS-treated mice. alpha-SMA positive cells were also detected in lung parenchyma after bleomycin treatment. Following concomitant treatment with anti-transforming growth factor-beta (TGF beta) antibody with bleomycin, the number of alpha-SMA-positive fibroblastic cells was significantly reduced up to 50%, along with the reduction of dermal sclerosis. To confirm the protein level of alpha-SMA, immunoblotting was carried out. Results showed an increase of alpha-SMA expression in lesional skin at 3 weeks of bleomycin treatment, which was reduced following anti-TGF-beta antibody treatment. These data suggest that fibroblastic cells are phenotypically altered into myofibroblasts during the fibrotic process in the experimental model of bleomycin-induced scleroderma, which was considered mediated, for the most part, by TGF-beta. Blockade of TGF-beta may be a therapeutic intervention for scleroderma. PMID- 11781071 TI - Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro. AB - Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro. Furthermore, we used ELISA to quantitate cytokine secretion after various passages in vitro. We demonstrate that in vitro culturing of established cell lines led to increases in the cell surface expression of MHC class I and ICAM-1 and secretion of IL-6 and TGF-beta(2). Furthermore, there were significant changes in the expression of MHC class I, MHC class II, B7-2, ICAM-1, and FasL when comparing ex vivo tumor cells to those after a single passage in vitro. After passaging once in vitro, there were also significant changes in the secretion of TGF-beta(2) and IL-10. This report indicates that in vitro culturing leads to significant changes in both cell surface molecules and secreted cytokines, which are known to affect the ability of immune cells to initiate an anti-tumor immune response. These changes in the immunological phenotype of glioblastomas after in vitro culturing may in part explain the limited success of immunotherapeutic strategies against glioblastomas in human clinical trials. PMID- 11781072 TI - Activated human CD4+ T cells induced by dendritic cell stimulation are most sensitive to transforming growth factor-beta: implications for dendritic cell immunization against cancer. AB - The secretion of immunosuppressive factors like transforming growth factor-beta (TGF-beta) by tumor cells has been recognized as one of the mechanisms involved in tumor immunological escape. This study aimed to examine whether dendritic cell (DC) immunization could reverse TGF-beta-induced immunosuppression by simulating the in vivo interaction among infused DCs, host T cells, and tumor-secreted TGF beta in an in vitro study. We found that both immature and mature DCs were relatively resistant to TGF-beta. The addition of TGF-beta to naive human CD4+ T cells, which are required by genetically modified DC to elicit antitumor immunity, resulted in their hyporesponsiveness to DC stimulation in a dose dependent manner. When activated by allogeneic DCs in the presence of TGF-beta, CD4+ T cells displayed a reduced capacity to proliferate. More importantly, activated CD4+ T cells induced by DC stimulation were very sensitive to TGF-beta, and this susceptibility was enhanced by their previous exposure to TGF-beta. The underlying mechanism was linked to TGF-beta-induced apoptosis of activated T cells. However, the presence of stimulation from DC or antibodies to CD3 plus CD28 could partly reverse the immunosuppressive effect of TGF-beta on activated CD4+ T cells. Taken together, our results indicate that the efficacy of DC immunization may be impaired by tumor-derived TGF-beta. PMID- 11781073 TI - Glucocorticoids suppress the inflammation-mediated tolerance to acute toxicity of cadmium in mice. AB - Several compounds have been shown to cause acute toxicity to cadmium (Cd). The mechanism of tolerance to Cd toxicity induced by glucocorticoids or by inflammation involves induction of metallothionein (MT) synthesis via glucocorticoid response elements or by inflammatory cytokines. We have demonstrated previously that the synthetic glucocorticoid dexamethasone suppresses inflammation-mediated induction of hepatic MT synthesis. Here we investigated the effect of glucocorticoid on tolerance to Cd induced by inflammation in mice. The LD50 of Cd for mice with induced inflammation by injection with turpentine oil (Tur-mice) was higher than the LD50 in control mice. Pretreatment of Tur-mice with dexamethasone to the Tur-mice (Dex+Tur-mice) resulted in a decrease in LD50 after Cd treatment. A significant increase in plasma alanine aminotransferase and aspartate aminotransferase levels in the Dex+Tur-mice was observed at lower doses of Cd than in the Tur-mice and at higher doses of Cd than in control mice. Dexamethasone did not suppress tolerance to cadmium toxicity in the testes of the Tur-mice. Pretreatment of Tur-mice with dexamethasone resulted in suppression of both plasma interleukin (IL)-6 elevation and in suppression of hepatic MT levels when induced by inflammation but not when induced by Cd. These data suggest that suppression of tolerance to Cd toxicity induced by glucocorticoid may involve hepatic MT synthesis mediated by inflammatory cytokines, such as IL-6. We suggest that the inflammatory response can modulate Cd toxicity by induction of MT by inflammatory cytokines. PMID- 11781074 TI - Chronic exposure to carbon monoxide and nicotine: endothelin ET(A) receptor antagonism attenuates carbon monoxide-induced myocardial hypertrophy in rat. AB - The aims of the present study were to determine the effects of endothelin ET(A) receptor antagonism on carbon monoxide (CO)-induced cardiac hypertrophy and endothelin-1 (ET-1) expression and to compare myocardial effects of chronic nicotine with CO exposure. Female Sprague-Dawley rats (n = 84) were randomized to three groups exposed 20 h/day to CO (200 ppm), nicotine (500 microg/m3), or air for 14 consecutive days. In each exposure group, animals were randomized to ET(A) receptor antagonist LU 135252 in drinking water (0.5 mg/ml) or placebo. Myocardial ET-1 and atrial natriuretic peptide (ANP) expression was measured by competitive RT-PCR and plasma ET-1 by immunoassay. Carboxyhemoglobin was 22.1 +/- 0.3% in CO-exposed animals and 2.8 +/- 0.3% in controls. Plasma nicotine was 57 +/- 7 ng/ml and plasma cotinine was 590 +/- 23 ng/ml in nicotine-exposed animals and below detection levels in controls. CO exposure induced a 21% increase in right ventricular hypertrophy (p < 0.01), a 7% increase in left ventricular hypertrophy (p < 0.01), a 25% increase in right ventricular ET-1 expression (p < 0.05), and an eightfold increase in ANP expression (p = 0.08). ET(A) receptor antagonism reduced right ventricular hypertrophy by 60% (p < 0.05) with no significant effect on left ventricular hypertrophy or myocardial ET-1 expression. Chronic nicotine exposure did not significantly affect cardiac weights or ANP and ET-1 expression. We conclude that ET(A) receptor antagonism reduces right ventricular hypertrophy induced by chronic CO exposure, whereas CO-induced myocardial ET-1 expression remains unchanged. PMID- 11781075 TI - Dioxin increases reactive oxygen production in mouse liver mitochondria. AB - Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) causes an oxidative stress response in liver and several extrahepatic tissues. The subcellular sources and underlying mechanisms of dioxin-induced reactive oxygen, however, are not well understood. In this study, we examined whether mitochondria, organelles that consume the majority of cellular oxygen, might be a source of dioxin-induced reactive oxygen. Female C57BL/6 mice were treated with dioxin (15 microg/kg body wt ip) on 3 consecutive days, and liver mitochondria were examined at 1, 4, and 8 weeks after the first treatment. Mitochondrial aconitase activity, an enzyme inactivated by superoxide, was decreased by 44% at 1 week, 22% at 4 weeks, and returned to control levels at 8 weeks. Dioxin elevated succinate-stimulated mitochondrial H2O2 production twofold at 1 and 4 weeks; H2O2 production remained significantly elevated at 8 weeks. The enhanced H2O2 production was due to neither increased Mn-superoxide dismutase activity nor decreased mitochondrial glutathione peroxidase activity. Dioxin treatment augmented mitochondrial glutathione, but not glutathione disulfide levels, a result that might be explained by increased mitochondrial glutathione reductase activity. Liver ATP levels were significantly lowered at 1 and 4 weeks, the peak times of mitochondrial reactive oxygen production. Increased dioxin-stimulated reactive oxygen at 1 and 4 weeks did not appear to be related to the observed decrease in cytochrome oxidase activity, since State 3 and State 4 respiration were not diminished. To our knowledge, this is the first report to show that dioxin increases mitochondrial respiration-dependent reactive oxygen production, which may play an important role in dioxin-induced toxicity and disease. PMID- 11781076 TI - Phytosterols act as endocrine and metabolic disruptors in the European polecat (Mustela putorius). AB - Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein-cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS. PMID- 11781077 TI - Chlorpyrifos oxon potentiates diacylglycerol-induced extracellular signal regulated kinase (ERK 44/42) activation, possibly by diacylglycerol lipase inhibition. AB - Chlorpyrifos oxon (CPO) activates extracellular signal-regulated kinase (ERK 44/42) in Chinese hamster ovary (CHOK1) cells but the mechanism is not defined. This study tests the hypothesis that diacylglycerol (DAG) is the secondary messenger responsible for CPO-induced ERK 44/42 activation. It is known that DAG is sequentially hydrolyzed by DAG lipase and monoacylglycerol (MAG) lipase, both of which are organophosphate sensitive. Inhibition of these enzymes might therefore lead to the accumulation of DAG and MAG, of which only DAG is a secondary messenger. The experiments show that treatment of CHOK1 cells with CPO significantly inhibits DAG/MAG lipase activity and elevates cellular DAG levels. Pretreatment of CHOK1 cells with CPO or a carbamate known to be a DAG lipase inhibitor, followed by treatment with a cell-permeable DAG (1,2-dihexanoyl-sn glycerol), results in synergistic activation of ERK 44/42. CPO-potentiated DAG induced ERK 44/42 activation is both time and concentration dependent. This activation is blocked by inhibitors of protein kinase C and mitogen-activated protein kinase kinase, suggesting that these enzymes are important in CPO/DAG cellular signaling. Activation by a stable DAG analogue (phorbol ester) was not altered by CPO, suggesting that DAG metabolism is the probable target for CPO potentiated DAG-induced ERK 44/42 activation. These observations support the hypothesis that CPO potentiates DAG signaling in CHOK1 cells by inhibiting a CPO sensitive DAG lipase, thereby providing a potential mechanism of toxicity not associated with acetylcholinesterase inhibition. PMID- 11781078 TI - Phospholipase A2-mediated Ca2+ influx by 2,2',4,6-tetrachlorobiphenyl in PC12 cells. AB - Polychlorinated biphenyls (PCBs) are a group of persistent and widespread environmental pollutants, and known to affect signaling molecules. Phospholipase A2 (PLA2) mediates cellular destructive processes as well as normal physiological responses in neuronal cells. In this study, we examined whether PLA2 can be activated by PCBs in PC12 cells. Of the congeners tested, ortho-substituted PCBs were found to induce PLA2 activation. PLA2 activation by 2,2',4,6 tetrachlorobiphenyl (TeCB), the most potent congener, was inhibited by bromoenol lactone (BEL), a calcium-independent PLA2 (iPLA2) inhibitor, and methyl arachidonyl fluorophosphonate (MAFP), a cytosolic PLA2 and iPLA2 inhibitor. In the case of Ca2+, although 2,2',4,6-TeCB increased [Ca2+]i in the presence of extracellular Ca2+, PLA2 activation was not inhibited by EGTA and 1,2-bis (o aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxy-methyl) ester, an extracellular and an intracellular Ca2+ chelator, respectively. On the other hand, 2,2',4,6-TeCB-induced Ca2+ increase was partially inhibited by BEL and MAFP. In addition, 2,2',4,6-TeCB induced apoptotic cell death in these cells. Taken together, our results suggest that ortho-substituted PCBs might induce apoptosis through PLA2-mediated Ca2+ influx, which provides a clue to understand the mechanism of neurotoxic effects of ortho-substituted PCBs. PMID- 11781079 TI - Lead-stimulated p38MAPK-dependent Hsp27 phosphorylation. AB - Lead (Pb2+) is a cytotoxic metal ion whose mechanism of action is not established. However, Pb2+ is known to interact with a wide variety of molecules involved in signal transduction. In this study the effect of Pb2+ on protein phosphorylation in bovine adrenal chromaffin cells and human SH SY5Y cells was examined. Cells were incubated with 32P(i) for 1 h in the presence of Pb2+ (1-10 microM) and the proteins were separated by two-dimensional PAGE. An increase in the phosphorylation of a number of proteins was observed in response to Pb2+, including three spots, MW 25 kDa, and pI's in the range 4.0-4.5. These proteins were immunoidentified as three isoforms of the heat-shock protein 27 kDa (Hsp27), and the identity of the most basic spot was confirmed by amino acid sequencing. Phosphorylation of p38MAPK was increased by Pb2+ and the effect of Pb2+ on Hsp27 phosphorylation was blocked by the p38MAPK inhibitor SB203580 (1 microM). The results were similar for bovine chromaffin cells and human SH SY5Y cells. This is the first report showing that Pb2+ can modulate the phosphorylation state of Hsp27 via activation of the p38MAPK pathway. PMID- 11781081 TI - Chromophore distortions in the bacteriorhodopsin photocycle: evolution of the H C14-C15-H dihedral angle measured by solid-state NMR. AB - In recent years, structural information about bacteriorhodopsin has grown substantially with the publication of several crystal structures. However, precise measurements of the chromophore conformation in the various photocycle states are still lacking. This information is critical because twists about the chromophore backbone chain can influence the Schiff base nitrogen position, orientation, and proton affinity. Here, we focus on the C14-C15 bond, using solid state nuclear magnetic resonance spectroscopy to measure the H-C14-C15-H dihedral angle. In the resting state (bR(568)), we obtain an angle of 164 +/- 4 degrees, indicating a 16 degrees distortion from a planar all-trans chromophore. The dihedral angle is found to decrease to 147 +/- 10 degrees in the early M intermediate (M(o)) and to 150 +/- 4 degrees in the late M intermediate (M(n)). These results demonstrate changes in the chromophore conformation undetected by recent X-ray diffraction studies. PMID- 11781080 TI - Acute exposure to methylmercury opens the mitochondrial permeability transition pore in rat cerebellar granule cells. AB - Cerebellar granule cells are preferentially targeted during methylmercury (MeHg) poisoning. Following acute MeHg exposure, granule cells in culture undergo an increase in intracellular Ca2+ concentration ([Ca2+]i) that apparently contributes to cell death. This effect consists of several temporally and kinetically distinct phases. The initial elevation arises from release of Ca2+(i) stores; the second phase results from entry of Ca2+(e). In these experiments, we tested the hypothesis that release of mitochondrial Ca2+ through the mitochondrial permeability transition pore (MTP) contributes to the initial release of Ca2+(i). Neonatal rat cerebellar granule cells in culture and single cell microfluorimetry were used to examine MeHg-induced changes in [Ca2+]i and mitochondrial membrane potential (Psi(m)). Pretreatment with the MTP inhibitor cyclosporin A (CsA, 5 microM) delayed the initial phase of increased [Ca2+]i induced by 0.2 and 0.5 microM MeHg, but not 1.0 microM MeHg. CsA (5 microM) also delayed the irreversible loss of Psi(m) induced by 0.5 microM MeHg. Ca2+(e) was not required for either effect, because the effect of CsA on the first phase increase in [Ca2+]i and loss of Psi(m) was not altered in nominally Ca2+-free buffer. Increasing concentrations of MeHg (0.2-2.0 microM) caused increasing incidence of cell death at 24 h postexposure. Treatment with CsA provided protection against cytotoxicity at lower MeHg concentrations (0.2-0.5 microM), but not at higher MeHg concentrations (1.0-2.0 microM). Thus, the MTP appears to play a significant role in the cellular effects following acute exposure of cerebellar granule neurons to MeHg. PMID- 11781082 TI - Carotenoid S(1) state in a recombinant light-harvesting complex of Photosystem II. AB - The carotenoid species lutein, violaxanthin, and zeaxanthin are crucial in the xanthophyll-dependent nonphotochemical quenching occurring in photosynthetic systems of higher plants, since they are involved in dissipation of excess energy and thus protect the photosynthetic machinery from irreversible inhibition. Nonetheless, important properties of the xanthophyll cycle carotenoids, such as the energy of their S(1) electronic states, are difficult to study and were only recently determined in organic solvents [Polivka, T. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 4914. Frank, H. A. (2000) Biochemistry 39, 2831]. In the present study, we have determined the S(1) energies of three carotenoid species, violaxanthin, lutein, and zeaxanthin, in their LHCII (peripheral light-harvesting complex of photosystem II) protein environment by constructing recombinant Lhcb1 (Lhc = light-harvesting complex) proteins containing single carotenoid species. Within experimental error the S(1) energy is the same for all three carotenoids in the monomeric LHCII, 13,900 +/- 300 cm(-1) (720 +/- 15 nm), thus well below the Q(y)() transitions of chlorophylls. In addition, we have found that, although the S(1) lifetimes of violaxanthin, lutein, and zeaxanthin differ substantially in solution, when incorporated into the LHCII protein, their S(1) states have in fact the same lifetime of about 11 ps. Despite the similar spectroscopic properties of the carotenoids bound to the LHCII, we observed a maximal fluorescence quenching when zeaxanthin was present in the LHCII complex. On the basis of these observations, we suggest that, rather than different photochemical properties of individual carotenoid species, changes in the protein conformation induced by binding of carotenoids with distinct molecular structures are involved in the quenching phenomena associated with Lhc proteins. PMID- 11781083 TI - Solvent kinetic isotope effects monitor changes in hydrogen bonding at the active center of yeast pyruvate decarboxylase concomitant with substrate activation: the substituent at position 221 can control the state of activation. AB - Substrate activation of yeast pyruvate decarboxylase has been studied extensively in the authors' laboratories providing strong evidence that interaction of substrate with residue C221 provides the trigger, and the information is then transmitted along the C221 to H92 to E91 to W412 to G413 pathway to the 4'-amino nitrogen of the thiamin diphosphate cofactor. Earlier, it was found that the C221S substitution reduced the Hill coefficient from 2.0 to 0.8-0.9, the C221A substitution to 1.0, even though C221 is located on the beta domain some 20 A from the active center thiamin diphosphate cofactor, which is at the interface of the alpha and gamma domains. Here are reported experiments on the C221D/C222A and C221E/C222A variants, in which a negative charge is built onto the C221 side chain, to better mimic the effect of a pyruvate molecule covalently bonded to C221 as a thiohemiketal. Both variants were purified to an optimal activity of 70% of the wild-type enzyme, higher activity than that with the earlier uncharged substitutions at this position. The Hill coefficient for both variants is exactly 1.0. The deuterium solvent kinetic isotope effects (SKIE) on k(cat) for these variants were similar to that for the wild-type enzyme and the C221A/C222A variant, suggesting that starting with the first irreversible step (decarboxylation) the rate-limiting transition states are very similar for all of these enzyme forms. In contrast, such SKIE on k(cat)/K(m) are quite different for the C221A/C222A variant (0.62) than for the C221E/C222A or C221D/C222A variants (0.80-0.82), clearly indicating the effect of the C221 substitutions on transition states starting with the binding of the first substrate to the enzyme and terminating with the decarboxylation step. The results provide strong additional evidence for the involvement of residue C221 in the substrate activation process and suggest that the C221D (C221E) substitution shifts the enzyme into a conformation that resembles the activated conformation. A comparison with SKIE for the wild-type enzyme provides insight to changes in hydrogen bonding at the active center as a result of substrate activation. PMID- 11781084 TI - A comprehensive model for the allosteric regulation of mammalian ribonucleotide reductase. Functional consequences of ATP- and dATP-induced oligomerization of the large subunit. AB - Reduction of NDPs by murine ribonucleotide reductase (mRR) requires catalytic (mR1) and free radical-containing (mR2) subunits and is regulated by nucleoside triphosphate allosteric effectors. Here we present a new, comprehensive, and quantitative model for allosteric control of mRR enzymatic activity based on molecular mass, ligand binding, and enzyme activity studies. In this model, nucleotide binding to the specificity site (s-site) drives formation of an active R1(2)R2(2) dimer, ATP or dATP binding to the adenine-specific site (a-site) results in formation of an inactive tetramer, and ATP binding to the newly described hexamerization site (h-site) drives formation of active R1(6)R2(6) hexamer. In contrast, an earlier phenomenological model [Thelander, L., and Reichard, P. (1979) Annu. Rev. Biochem. 67, 71-98] (the "RT" model) ignores aggregation state changes and mistakenly rationalizes ATP activation versus dATP inhibition as reflecting different functional consequences of ATP versus dATP binding to the a-site. Our results suggest that the R1(6)R2(6) heterohexamer is the major active form of the enzyme in mammalian cells, and that the ATP concentration is the primary modulator of enzyme activity, coupling the rate of DNA biosynthesis with the energetic state of the cell. Using the crystal structure of the Escherichia coliR1 hexamer as a model for the mR1 hexamer, a scheme is presented that rationalizes the slow isomerization of the tetramer form and suggests an explanation for the low enzymatic activity of tetramers complexed with R2. The similar specific activities of R1(2)R2(2) and R1(6)R2(6) are inconsistent with a proposed model for R2(2) docking with R1(2) [Uhlin, U., and Eklund, H. (1994) Nature 370, 533-539], and an alternative is suggested. PMID- 11781085 TI - Structure and orientation of sarcolipin in lipid environments. AB - Sarcolipin (SLN) is a 31 amino acid integral membrane protein that regulates Ca ATPase activity in skeletal muscle. Here, we report the three-dimensional structure and topology of synthetic SLN in lipid environments, as determined by solution and solid-state NMR spectroscopy. 2D solution NMR experiments were performed on SLN solubilized in sodium dodecyl sulfate (SDS) micelles. We found that SLN adopts a highly defined alpha-helical conformation from F9 through R27, with a backbone RMSD of 0.65 A and a side chain RMSD of 1.66 A. The N-terminus (M1 through L8) and the C-terminus (S28 through Y31) are mostly unstructured. The orientation of the SLN was determined using one-dimensional (15)N NMR solid-state spectroscopy. The protein was incorporated into phospholipid bilayers prepared from a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn glycero-3-phosphoethanolamine. The (15)N chemical shift solid-state spectra from selectively labeled SLN samples indicate that SLN orients perpendicularly to the plane of the membrane bilayers. These results support the proposed mechanism of Ca-ATPase regulation of SLN via protein-protein intramembranous interactions between the highly conserved transmembrane domains of the Ca-ATPase and the conserved transmembrane domain of SLN. PMID- 11781087 TI - Molecular mechanisms of chaperonin GroEL-GroES function. AB - The dynamics of the GroEL-GroES complex is investigated with a coarse-grained model. This model is one in which single-residue points are connected to other such points, which are nearby, by identical springs, forming a network of interactions. The nature of the most important (slowest) normal modes reveals a wide variety of motions uniquely dependent upon the central cavity of the structure, including opposed torsional rotation of the two GroEL rings accompanied by the alternating compression and expansion of the GroES cap binding region, bending, shear, opposed radial breathing of the cis and trans rings, and stretching and contraction along the protein assembly's long axis. The intermediate domains of the subunits are bifunctional due to the presence of two hinges, which are alternatively activated or frozen by an ATP-dependent mechanism. ATP binding stabilizes a relatively open conformation (with respect to the central cavity) and hinders the motion of the hinge site connecting the intermediate and equatorial domains, while enhancing the flexibility of the second hinge that sets in motion the apical domains. The relative flexibilities of the hinges are reversed in the nucleotide-free form. Cooperative cross correlations between subunits provide information about the mechanism of action of the protein. The mechanical motions driven by the different modes provide variable binding surfaces and variable sized cavities in the interior to enable accommodation of a broad range of protein substrates. These modes of motion could be used to manipulate the substrate's conformations. PMID- 11781088 TI - Antigene effect in K562 cells of a PEG-conjugated triplex-forming oligonucleotide targeted to the bcr/abl oncogene. AB - Triplex-forming oligonucleotides are able to modulate gene expression by site specific binding to genomic DNA. Their use as therapeutic agents is limited by inefficient cellular uptake, scarce nuclear internalization, and oligonucleotide self-aggregation. In this study, we demonstrate that a 13-mer AG motif oligonucleotide covalently linked to a high-molecular mass (9000 Da) polyethylene glycol (PEG ODN(13)) exhibits uptake and biological properties that are superior to those of the nonconjugated isosequence analogue (free ODN(13)). Band-shift and footprinting experiments showed that PEG ODN(13) forms a stable triple helix (apparent K(d) between 10(-6) and 10(-7) M in 50 mM Tris-acetate, 10 mM MgCl(2), pH 7.4, 37 degrees C) with a natural polypurine-polypyrimidine target located in the 5' flanking region of the human bcr/abl oncogene. Confocal laser microscopy performed on unfixed live cells stained with hexidium iodide as well as on glass fixed cells stained with propidium iodide showed that fluorescein-labeled PEG ODN(13) is far more efficiently taken up and internalized in the nucleus by K562 and HeLa cells than the nonconjugated free ODN(13). It was found that PEG ODN(13) specifically downregulated the transcription of bcr/abl mRNA at 65 +/- 5% with respect to control and inhibited cell growth by 32 +/- 3% in a 3 day liquid culture assay. Moreover, PEG ODN(13) was more resistant against S1 and fetal bovine serum nucleases than free ODN(13), and less inclined to self-associate into multistrand structures in solution. Taken together, these results provide useful elements for designing artificial transcription repressors with enhanced potency in vivo. PMID- 11781086 TI - alpha-Crystallin chaperone-like activity and membrane binding in age-related cataracts. AB - alpha-Crystallin, the major protein component of the vertebrate lens, is thought to play a critical role in the maintenance of transparency through its ability to inhibit stress-induced protein aggregation. However, during aging and cataract formation the amount of membrane-bound alpha-crystallin increases significantly while high molecular weight complexes (HMWCs) comprised of alpha-crystallin and other lens crystallins accumulate. These and other recent data suggest a possible link between cataract formation, the formation of high molecular weight alpha crystallin aggregates, and the progressive increase in membrane association of alpha-crystallin. To better understand these processes, we characterized the chaperone-like activity (CLA) and subunit exchange of membrane bound alpha crystallin. In addition, we measured the membrane binding properties of in vitro constituted HMWCs to understand the mechanism by which increased alpha-crystallin is bound to the membrane of old and cataractous lens cells in vivo. Membrane associated alpha-crystallin complexes have measurably reduced CLA compared to complexes in solution; however, membrane binding does not alter the time required for alpha-crystallin complexes to reach subunit exchange equilibrium. In addition, HMWCs prepared in vitro have a profoundly increased membrane binding capacity as compared to native alpha-crystallin. These results are consistent with a model in which increased membrane binding of alpha-crystallin is an integral step in the pathogenesis of many forms of cataracts. PMID- 11781089 TI - Role of residue 147 in the gene regulatory function of the Escherichia coli purine repressor. AB - The crystal structures of corepressor-bound and free Escherichia coli purine repressor (PurR) have delineated the roles of several residues in corepressor binding and specificity and the intramolecular signal transduction (allosterism) of this LacI/GalR family member. From these structures, residue W147 was implicated as a key component of the allosteric response, but in many members of the LacI/GalR family, position 147 is occupied by an arginine. To understand the role of this tryptophan at position 147, three proteins, substituted by phenylalanine (W147F), alanine (W147A), or arginine (W147R), were constructed and characterized in vivo and in vitro, and their structures were determined. W147F displays a decreased affinity for corepressor and is a poor repressor in vivo. W147A and W147R, on the other hand, are super repressors and bind corepressor 13.6 and 7.9 times more tightly, respectively, than wild-type. Each mutant PurR hypoxanthine-purF operator holo complex crystallizes isomorphously to wild-type. Whereas the apo corepressor binding domain (CBD) of W147F crystallizes under those conditions used for the wild-type protein, neither the apo CBD of W147R nor W147A crystallizes, although screened extensively for new crystal forms. Structures of the holo repressor mutants have been solved to resolutions between 2.5 and 2.9 A, and the structure of the apo CBD of W147F has been solved to 2.4 A resolution. These structures provide insight into the altered biochemical properties and physiological functions of these mutants, which appear to depend on the sometimes subtle preference for one conformation (apo vs holo) over the other. PMID- 11781090 TI - GTP hydrolysis of cell division protein FtsZ: evidence that the active site is formed by the association of monomers. AB - The essential prokaryotic cell division protein FtsZ is a tubulin homologue that forms a ring at the division site. FtsZ forms polymers in a GTP-dependent manner. Recent biochemical evidence has shown that FtsZ forms multimeric structures in vitro and in vivo and functions as a self-activating GTPase. Structural analysis of FtsZ points to an important role for the highly conserved tubulin-like loop 7 (T7-loop) in the self-activation of GTP hydrolysis. The T7-loop was postulated to form the active site together with the nucleotide-binding site on an adjacent FtsZ monomer. To characterize the role of the T7-loop of Escherichia coli FtsZ, we have mutagenized residues M206, N207, D209, D212, and R214. All the mutant proteins, except the R214 mutant, are severely affected in polymerization and GTP hydrolysis. Charged residues D209 and D212 cannot be substituted with a glutamate residue. All mutants interact with wild-type FtsZ in vitro, indicating that the T7-loop mutations do not abolish FtsZ self-association. Strikingly, in mixtures of wild-type and mutant proteins, most mutants are capable of inhibiting wild type GTP hydrolysis. We conclude that the T7-loop is part of the active site for GTP hydrolysis, formed by the association of two FtsZ monomers. PMID- 11781091 TI - Uncoupling the ATPase activity of the N-ethylmaleimide sensitive factor (NSF) from 20S complex disassembly. AB - The N-ethylmaleimide sensitive factor (NSF) plays a critical role in intracellular trafficking by disassembling soluble NSF attachment protein receptor (SNARE ) complexes. The NSF protomer consists of three domains (NSF-N, NSF-D1, and NSF-D2). Two domains (NSF-D1 and NSF-D2) contain a conserved approximately 230 amino acid cassette, which includes a distinctive motif termed the second region of homology (SRH) common to all ATPases associated with various cellular activities (AAA). In hexameric NSF, several SRH residues become trans elements of the ATP binding pocket. Mutation of two conserved arginine residues in the NSF-D1 SRH (R385A and R388A) did not effect basal or soluble NSF attachment protein (SNAP)-stimulated ATPase activity; however, neither mutant underwent ATP-dependent release from SNAP-SNARE complexes. A trans element of the NSF-D2 ATP binding site (K631) has been proposed to limit the ATPase activity of NSF-D2, but a K631D mutant retained wild-type activity. A mutation of the equivalent residue in NSF-D1 (D359K) also did not affect nucleotide hydrolysis activity but did limit NSF release from SNAP-SNARE complexes. These trans elements of the NSF-D1 ATP binding site (R385, R388, and D359) are not required for nucleotide hydrolysis but are important as nucleotide-state sensors. NSF-N mediates binding to the SNAP-SNARE complex. To identify the structural features required for binding, three conserved residues (R67, S73, and Q76) on the surface of NSF-N were mutated. R67E completely eliminated binding, while S73R and Q76E showed limited effect. This suggests that the surface important for SNAP binding site lies in the cleft between the NSF-N subdomains adjacent to a conserved, positively charged surface. PMID- 11781092 TI - Two glutamate residues, Glu 208 alpha and Glu 197 beta, are crucial for phosphorylation and dephosphorylation of the active-site histidine residue in succinyl-CoA synthetase. AB - Succinyl-CoA synthetase catalyzes the reversible reaction succinyl-CoA + NDP + P(i) <--> succinate + CoA + NTP (N denoting adenosine or guanosine). The enzyme consists of two different subunits, designated alpha and beta. During the reaction, a histidine residue of the alpha-subunit is transiently phosphorylated. This histidine residue interacts with Glu 208 alpha at site I in the structures of phosphorylated and dephosphorylated Escherichia coli SCS. We postulated that Glu 197 beta, a residue in the nucleotide-binding domain, would provide similar stabilization of the histidine residue during the actual phosphorylation/dephosphorylation by nucleotide at site II. In this work, these two glutamate residues have been mutated individually to aspartate or glutamine. Glu 197 beta has been additionally mutated to alanine. The mutant proteins were tested for their ability to be phosphorylated in the forward or reverse direction. The aspartate mutant proteins can be phosphorylated in either direction, while the E208 alpha Q mutant protein can only be phosphorylated by NTP, and the E197 beta Q mutant protein can only be phosphorylated by succinyl CoA and P(i). These results demonstrate that the length of the side chain at these positions is not critical, but that the charge is. Most significantly, the E197 beta A mutant protein could not be phosphorylated in either direction. Its crystal structure shows large differences from the wild-type enzyme in the conformation of two residues of the alpha-subunit, Cys 123 alpha-Pro 124 alpha. We postulate that in this conformation, the protein cannot productively bind succinyl-CoA for phosphorylation via succinyl-CoA and P(i). PMID- 11781093 TI - Crowding by trisaccharides and the 2:1 cytochrome c-cytochrome c peroxidase complex. AB - Proteins are designed to function under crowded conditions where the solute concentration can reach 400 g/L, but they are almost always studied in dilute solutions. To address this discrepancy, we have undertaken a series of studies to determine the effects of high solute concentrations on the thermodynamics of protein equilibria. Recently, we used isothermal titration calorimetry (ITC) to show that high concentrations of mono-, di-, and tetrasaccharides have a small stabilizing effect on the crystallographically defined cytochrome c binding site on yeast ferricytochrome c peroxidase [Morar, A. S., Wang, X., and Pielak, G. J. (2001) Biochemistry 40, 281-285]. Here, we use this technique to show that trisaccharides increase the apparent thermodynamic binding constants for both cytochrome c binding sites on the peroxidase. Mutagenesis studies confirm that the second site includes Asp 148 on the peroxidase. Binding of both cytochrome c molecules is exothermic. The data are interpreted by assuming either the presence or absence of intersite interactions. PMID- 11781094 TI - Unusual properties of plastocyanin from the fern Dryopteris crassirhizoma. AB - The effect of pH on the (1)H NMR spectrum, reduction potential, and self-exchange rate constant of the novel plastocyanin (PCu) from the fern plant Dryopteris crassirhizoma has been studied. The results are compared with those for the higher-plant PCu from parsley. In the (1)H NMR spectrum of D. crassirhizoma PCu(I), there is no sign that either of the His ligands is protonated at pH* down to 5.4. The reduction potentials of D. crassirhizoma and parsley PCu are 382 and 379 mV, respectively, at pH 7.4. When the pH value is decreased, the reduction potential of parsley PCu is seen to increase quite dramatically, consistent with protonation at His87 in PCu(I). A pK(a) of 5.8 is obtained from the electrochemistry data, consistent with a value of 5.6 determined by NMR. The reduction potential of D. crassirhizoma PCu exhibits a much less pronounced dependence on pH. The self-exchange rate constant of D. crassirhizomaPCu(I) is 3.4 x 10(3) M(-1) s(-1) at pH* 7.9. This is the smallest self-exchange rate constant reported to date for a PCu and can be rationalized by considering the altered distribution of charged residues on the surface of the D. crassirhizoma protein compared to the charge distributions of other higher-plant PCus. The self exchange rate constant increases to 9 x 10(3) M(-1) s(-1) at pH* 5.4, consistent with enhanced protein-protein association at lower pH*, and the absence of His87 protonation in D. crassirhizoma PCu(I) in the accessible pH range. PMID- 11781096 TI - Biosynthesis and post-translational processing of site-directed endoproteolytic cleavage mutants of Pro-CCK in AtT-20 cells. AB - Site-directed mutagenesis in which individual cleavage site P1 amino acids were changed to Ala was performed to delineate their importance in the processing of pro-CCK in mouse pituitary tumor AtT-20 cells. Individual substitution of cleavage sites on pro-CCK, viz., CCK 58 cleavage site R/A to A/A, CCK 33 cleavage site R/K to A/K, CCK 22 cleavage site K/N to A/N, and CCK 8 cleavage site R/D to A/D, did not inhibit pro-CCK expression or the production of some form of amidated CCK. Wild-type CCK cDNA expression in these cells results in production and secretion of CCK 8 and CCK 22. Substitution of the 58R/A cleavage site with A/A produces only CCK 33; 33A/K and 22A/N produce only CCK 8, whereas 8A/D produces CCK 12 and some CCK 22. Where the GRR residues on the C-terminus of CCK 8 were mutated to GAA, no amidated CCK was produced. Significant amounts of the pro-CCK, C-terminal peptide S9S was found in the medium of cells transfected with GAA mutant cDNA, indicating that this pro-CCK was cleaved at the GAA site probably by a nonprohormone convertase enzyme. Further analysis of the cells expressing the GAA mutant demonstrated that it is not extensively cleaved at other sites to produce CCK 8 GAA or larger peptides. In the mutant where the entire pro-CCK, C-terminal S9S was deleted, CCK 8 is processed and secreted normally. Thus, the cleavage at the C-terminal GRR site is essential for subsequent cleavages, and modification of other cleavage sites (58, 33, 22, and 8) has a major impact on pro-CCK processing. These results suggest that there is a temporal order of cleavages, and the structure of pro-CCK has a strong influence on where and whether pro-CCK is processed. PMID- 11781095 TI - Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C terminal PRK2 fragment. AB - The mechanism by which PDK1 regulates AGC kinases remains unclear. To further understand this process, we performed a yeast two-hybrid screen using PDK1 as bait. PKC-zeta, PKC-delta, and PRK2 were identified as interactors of PDK1. A combination of yeast two-hybrid binding assays and coprecipitation from mammalian cells was used to characterize the nature of the PDK1-PKC interaction. The presence of the PH domain of PDK1 inhibited the interaction of PDK1 with the PKCs. A contact region of PDK1 was mapped between residues 314 and 408. The interaction of PDK1 with the PKCs required the full-length PKC-zeta and -delta proteins apart from their C-terminal tails. PDK1 was able to phosphorylate full length PKC-zeta and -delta but not PKC-zeta and -delta constructs containing the PDK1 phosphorylation site but lacking the C-terminal tails. A C-terminal PRK2 fragment, normally produced by caspase-3 cleavage during apoptosis, inhibited PDK1 autophosphorylation by >90%. The ability of PDK1 to phosphorylate PKC-zeta and -delta in vitro was also markedly inhibited by the PRK2 fragment. Additionally, generation of the PRK2 fragment in vivo inhibited by >90% the phosphorylation of endogenous PKC-zeta by PDK1. In conclusion, these results show that the C-terminal tail of PKC is a critical determinant for PKC-zeta and -delta phosphorylation by PDK1. Moreover, the C-terminal PRK2 fragment acts as a potent negative regulator of PDK1 autophosphorylation and PDK1 kinase activity against PKC-zeta and -delta. As the C-terminal PRK2 fragment is naturally generated during apoptosis, this may provide a mechanism of restraining prosurvival signals during apoptosis. PMID- 11781097 TI - Eukaryotic initiation factor 2 alpha subunit associates with TGF beta receptors and 14-3-3 epsilon and acts as a modulator of the TGF beta response. AB - Schistosoma mansoni receptor kinase 1 (SmRK1) is a divergent member of the TGF beta receptor family. Intracellular proteins that associate with these receptors are likely to play an important role in signaling. 14-3-3 epsilon is a previously described cytoplasmic protein, which associates with both SmRK1 and the human type I TGF beta receptor (T beta RI); overexpression of 14-3-3 epsilon leads to enhanced TGF beta-mediated signaling by T beta RI. We now describe the identification of S. mansoni eukaryotic translation initiation factor 2 alpha subunit (eIF2 alpha), through its interaction with SmRK1 in a yeast two-hybrid assay. S. mansoni eIF2 alpha also interacts with human TGF beta receptors. Strongest association was demonstrated with kinase inactive receptors, particularly the type II TGF beta receptor (T beta RII). Both T beta RI and T beta RII phosphorylate eIF2 alpha in vitro, at sites other than the previously described eIF2 alpha phosphorylation sites. EIF2 alpha also modulates signaling by TGF beta receptors; however, in contrast to 14-3-3 epsilon, eIF2 alpha overexpression inhibits the TGF beta-driven response. These data suggest a novel function for eIF2 alpha in the TGF beta signaling pathway. In addition, we have demonstrated an independent interaction between eIF2 alpha and 14-3-3 epsilon. Coexpression of 14-3-3 epsilon with eIF2 alpha leads to the abrogation of the inhibitory effect of eIF2 alpha on TGF beta-mediated signaling. The interaction of these two regulatory proteins with each other and with the TGF beta receptors and their relative expression levels are likely to be important in fine-tuning the regulation of TGF beta signal transduction. PMID- 11781098 TI - Phe(303) in TMVI of the alpha(1B)-adrenergic receptor is a key residue coupling TM helical movements to G-protein activation. AB - We showed previously that Phe(303) in transmembrane segment (TM) VI of the alpha(1B)-adrenergic receptor, a highly conserved residue in G-protein-coupled receptors (GPCRs), is critically involved in receptor-activation and G-protein coupling [Chen, S. H., Lin, F., Xu, M., Hwa, J., and Graham, R. M. (2000) EMBO J. 19, 4265-4271]. Here, we show that saturation mutagenesis of Phe(303) results in a series of mutants with different levels of constitutive activity for inositol phosphate (IP) signaling. Mutants F303G and F303N showed neither basal nor agonist-stimulated IP turnover, whereas F303A displayed increased basal activity but an attenuated maximal response to (-)-epinephrine-stimulation. F303L, on the other hand, showed all features of a typical constitutively active GPCR with markedly increased basal activity and increased potency and efficacy of agonist stimulated IP signaling. All mutants displayed higher agonist-binding affinities than the wild-type receptor, and by thermal stability studies, those able to signal showed increased susceptibility to inactivation with an order of sensitivity (F303L > F303A > WT) directly related to their degree of constitutive activity. Using the substituted cysteine accessibility method (SCAM) and equilibrium binding studies, we further show that the F303A and F303L mutants result in TM helical movements that differ in accordance with their degree of constitutive activity. These findings, therefore, confirm and extend our previous data implicating Phe(303) as a key residue coupling TM helical movements to G protein-activation. PMID- 11781099 TI - Hydrolysis of ATP by polymerized actin depends on the bound divalent cation but not profilin. AB - Growing evidence suggests that the nucleotide bound to actin filaments serves as a timer to control actin filament turnover during cell motility (Pollard, T. D., Blanchoin, L., and Mullins, R. D. (2000) Annu. Rev. Biophys. Biomol. Struct. 29, 545-576). We re-examined the hydrolysis of ATP by polymerized actin using mechanical quenched-flow methods to improve temporal resolution. The rate constant for ATP hydrolysis by polymerized Mg actin is 0.3 s(-1), 3-fold faster than that measured manually. The ATP hydrolysis rate is similar when Mg ATP actin elongates either the pointed end or the barbed end of filaments. Polymerized Ca actin hydrolyzes ATP at 0.05 s(-1). Mg ATP actin saturated with profilin can elongate barbed ends at >60 s(-1), 2 orders of magnitude faster than ATP hydrolysis (0.3 s(-1)). Given that profilin binds to a surface on actin that is buried in the Holmes model of the actin filament, we expect that profilin will block subunit addition at the barbed end of a filament. Profilin must move from this site at rates much faster than it dissociates from monomers (4 s(-1)). ATP hydrolysis is not required for this movement. PMID- 11781100 TI - The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta. AB - To study whether protein kinase C (PKC) isoforms can interact with protein tyrosine-phosphatases (PTPs) which are connected to the insulin signaling pathway, we co-overexpressed PKC isoforms together with insulin receptor, docking proteins, and the PTPs SHP1 and SHP2 in human embryonic kidney (HEK) 293 cells. After phorbol ester induced activation of PKC isoforms alpha, beta 1, beta 2, and eta, we could show a defined gel mobility shift of SHP2, indicating phosphorylation on serine/threonine residues. This phosphorylation was not dependent on insulin receptor or insulin receptor substrate-1 (IRS-1) overexpression and did not occur for the closely related phosphatase SHP1. Furthermore, PKC phosphorylation of SHP2 was completely blocked by the PKC inhibitor bisindolylmaleimide and was not detectable when SHP2 was co overexpressed with kinase negative mutants of PKC beta 1 and -beta 2. The phosphorylation also occurred on endogenous SHP2 in Chinese hamster ovary (CHO) cells stably overexpressing PKC beta 2. Using point mutants of SHP2, we identified serine residues 576 and 591 as phosphorylation sites for PKC. However, no change of phosphatase activity by TPA treatment was detected in an in vitro assay. In summary, SHP2 is phosphorylated on serine residues 576 and 591 by PKC isoforms alpha, beta 1, beta 2, and eta. PMID- 11781101 TI - Trans membrane domain IV is involved in ion transport activity and pH regulation of the NhaA-Na(+)/H(+) antiporter of Escherichia coli. AB - We have previously shown that the activity of NhaA is regulated by pH and found mutations that affect dramatically the pH dependence of the rate but not the K(m) (for Na(+) and Li(+)) of NhaA. In the present work, we found that helix IV is involved both in ion translocation as well as in pH regulation of NhaA. Two novel types of NhaA mutants were found clustered in trans membrane segment (TMS) IV: One type (D133C, T132C, and P129L) affects the apparent K(m) of NhaA to the cations with no significant effect on the pH profile of the antiporter; no shift of the pH profile was found when the activity of these mutants was measured at saturating Na(+) concentration. In contrast, the other type of mutations (A127V and A127T) was found to affect both the K(m) and the pH dependence of the rate of NhaA whether tested at saturating Na(+) concentration or not. These results imply that residues involved in the ion translocation of NhaA may (A127) or may not (D133, T132, and P129) overlap with those affecting the pH response of the antiporter. All mutants cluster in the N-terminal half of the putative alpha helix IV, one type on one face, the other on the opposite. Cys accessibility test demonstrated that although D133C is located in the middle of TMS IV, it is inhibited by N-ethylmaleimide and is exposed to the cytoplasm. PMID- 11781102 TI - Structural features underlying the multisite phosphorylation of the A domain of the NF-AT4 transcription factor by protein kinase CK1. AB - The phosphorylation and dephosphorylation of the NF-AT family of transcription factors play a key role in the activation of T lymphocytes and in the control of the immune response. The mechanistic aspects of NF-AT4 phosphorylation by protein kinase CK1 have been studied in this work with the aid of a series of 27 peptides, reproducing with suitable modifications the regions of NF-AT4 that have been reported to be phosphorylated by this protein kinase. The largest parent peptide, representing the three regions A, Z, and L spanning amino acids 173-218, is readily phosphorylated by CK1 at seryl residues belonging to the A2 segment, none of which fulfill the canonical consensus sequence for CK1. An acidic cluster of amino acids in the linker region between domains A and Z is essential for high efficiency phosphorylation of the A2 domain, as shown by the increase in K(m) caused by a deletion of the linker region or a substitution of the acidic residues with glycines. Individual substitutions with alanine of each of the five serines in the A2 domain (S-177, S-180, S-181, S-184, and S-186) reduce the phosphorylation rate, the most detrimental effect being caused by Ser177 substitution which results in a 10-fold drop in V(max). On the contrary, the replacement of Ser177 with phosphoserine triggers a hierarchical effect with a dramatic improvement in phosphorylation efficiency, which no longer depends on the linker region for optimal efficiency. These data are consistent with a two phase phosphorylation mechanism of NF-AT4 by CK1, initiated by the linker region which provides a functional docking site for CK1 and allows the unorthodox phosphorylation of Ser177; once achieved, this phosphoserine residue primes the phosphorylation of other downstream seryl residues, according to a hierarchical mechanism typically exploited by CK1. PMID- 11781103 TI - G13A substitution affects the biochemical and physical properties of the elongation factor 1 alpha. A reduced intrinsic GTPase activity is partially restored by kirromycin. AB - The G13A substitution in the G13XXXXGK[T,S] consensus sequence of the elongation factor 1 alpha from the archaeon Sulfolobus solfataricus (SsEF-1 alpha) was introduced in order to study the reasons for selective differences found in the homologous consensus element AXXXXGK[T,S] of the other elongation factor EF-2 or EF-G. In a previous work, it was shown that the main effect of the A26G mutation was the activation of the intrinsic GTPase of SsEF-2 [De Vendittis, E., Adinolfi, B. S., Amatruda, M. R., Raimo, G., Masullo, M., and Bocchini, V. (1994) Eur. J. Biochem. 262, 600-605]. In this work, we found that, compared to the wild-type factor (SsEF-1 alpha wt), G13ASsEF-1 alpha shows (i) a reduced rate of [(3)H]Phe polymerization that was probably due to its reduced ability to form a ternary complex with heterologous aa-tRNA and (ii) a reduced intrinsic GTPase activity that was stimulated by high concentrations of NaCl (GTPase(Na)) [Masullo, M., De Vendittis, E., and Bocchini, V. (1994) J. Biol. Chem. 269, 20376-20379]. In addition, G13ASsEF-1 alpha showed an increased affinity for GDP and GTP. Surprisingly, the decreased intrinsic GTPase(Na) of G13ASsEF-1 alpha can be partially restored by kirromycin, an effect not found for SsEF-1 alpha wt. The temperature inducing a 50% denaturation of G13ASsEF-1 alpha was somewhat lower ( 5 degrees C) than that of SsEF-1 alpha wt, and the decrease in its thermophilicity was slightly more accentuated (-10 degrees C). These results indicate that the nature of the residue in position 13 is important for the functional and physical properties of SsEF-1 alpha. PMID- 11781104 TI - Efficiency of incision of an AP site within clustered DNA damage by the major human AP endonuclease. AB - A major DNA lesion induced by ionizing radiation and formed on removal of oxidized base lesions by various glycosylases is an apurinic/apyrimidinic site (AP site). The presence of an AP site within clustered DNA damage, induced following exposure to ionizing radiation or radiomimetic anticancer agents, may present a challenge to the repair machinery of the cell, if the major human AP endonuclease, HAP1, does not efficiently incise the AP site. In this study, specific oligonucleotide constructs containing an AP site located at several positions opposite to another damage [5,6-dihydrothymine (DHT), 8-oxoG, AP site, or various types of single strand breaks] on the complementary strand were used to determine the relative efficiency of the purified HAP1 protein in incising an AP site(s) from clustered DNA damage. A base damage (DHT and 8-oxoG) on the opposite strand has little or no influence on the rate of incision of an AP site by HAP1. In contrast, the presence of either a second AP site or various types of single strand breaks, when located one or three bases 3' to the base opposite to the AP site, has a strong inhibitory effect on the efficiency of incision of an AP site. The efficiency of binding of HAP1 to an AP site is reduced by approximately 1 order of magnitude if a single strand break (SSB) is located one or three bases 3' to the site opposite to the AP site on the complementary strand. If the AP site and either a SSB or a second AP site are located at any of the other positions relative to each other, a double strand break may result. PMID- 11781105 TI - Direct measurement of single-stranded DNA translocation by PcrA helicase using the fluorescent base analogue 2-aminopurine. AB - Use of the fluorescent base analogue 2-aminopurine has provided a direct demonstration of the translocation of PcrA helicase toward the 5'-end of single stranded DNA. Single 2-aminopurine bases are introduced into otherwise standard oligonucleotides and produce a fluorescence signal when PcrA reaches their position. We demonstrate that random binding of PcrA to ssDNA is followed by translocation in an ATP-dependent manner toward the 5'-terminus at 80 bases per second at 20 degrees C. The data also provide information on the kinetics of ssDNA binding to the helicase and of the protein dissociation from the 5'-end of ssDNA. A full kinetic model is presented for ATP-dependent DNA translocation by PcrA helicase. PMID- 11781106 TI - Biophysical characterization of the DNA binding and condensing properties of adenoviral core peptide mu. AB - Cationic peptides containing Lys and Arg residues interact with DNA via charge charge interactions and are known to play an important role in DNA charge neutralization and condensation processes. In this paper, we describe investigations of the interaction of the cationic adenovirus core complex peptide mu with a dodecameric ODN (12 bp) and pDNA (7528 bp) using a combination of fluorescence spectroscopy, circular dichroism spectroscopy, isothermal titration calorimetry, and photon correlation spectroscopy. Comparisons are made with protamine, a cationic peptide well-known for DNA charge neutralization and condensation. Equilibrium dissociation constants are derived independently by both CD and ITC methods for the interaction between protamine or mu with pDNA (K(d) = 0.6-1 microM). Thermodynamic data are also obtained by ITC, indicating strong charge-charge interactions. The interaction of protamine with pDNA takes place with decreasing entropy (-28.7 cal mol(-1) K(-1)); unusually, the interaction of mu with pDNA takes place with increasing entropy (Delta S degrees (bind) = 11.3 cal mol(-1) K(-1)). Although protamine and mu appear to destabilize pDNA double helix character to similar extents, according to CD thermal titration analyses, PCS studies show that interactions between mu and pDNA result in the formation of significantly more size-stable condensed particles than protamine. The enhanced flexibility and size stability of mu-DNA (MD) particles (80-110 nm) compared to protamine counterparts suggest that MD particles are ideal for use as a part of new nonviral gene delivery vectors. PMID- 11781107 TI - Solution structure of human apolipoprotein(a) kringle IV type 6. AB - The structure of apo(a) KIVT6 was investigated by two- and three-dimensional homo and heteronuclear NMR spectroscopy. The solution structure of apo(a) KIVT6 contains only a small amount of regular secondary structure elements, comprising a short piece of antiparallel beta-sheet formed by residues Trp62-Tyr64 and Trp72 Tyr74, a short piece of parallel beta-sheet formed by the residues Cys1-Tyr2 and Thr78-Gln79, and a small 3(10)-helix within residues Thr38-Tyr40. The backbone as well as the side chains are arranged in a way similar to those of apo(a) KIVT7, apo(a) KIVT10, and plasminogen K4. We determined additionally the K(d) value of 0.31 +/- 0.04 mM for the binding of epsilon-aminocaproic acid (EACA) to apo(a) KIVT6 and mapped the binding region on apo(a) KIVT6 by means of chemical shift perturbation. This lysine binding activity, which was reported to occur within apo(a) KIVT5-8, is functionally different from the lysine binding activity found for apo(a) KIVT10. PMID- 11781108 TI - Role of arginine 59 in the gamma-class carbonic anhydrases. AB - The functional role of the highly conserved active site Arg 59 in the prototype of the gamma-class carbonic anhydrase Cam (carbonic anhydrase from Methanosarcina thermophila) was investigated. Variants (R59A, -C, -E, -H, -K, -M, and -Q) were prepared by site-directed mutagenesis and characterized by size exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, and stopped-flow kinetic analyses. CD spectra indicated similar secondary structures for the wild type and the R59A and -K variants, independent of nondenaturing concentrations of guanidine hydrochloride (GdnHCl). SEC indicated that all variants purified as homotrimers like the wild type. SEC also revealed that the R59A and -K variants unfolded at > or = 1.5 M GdnHCl, compared to 3.0 M GdnHCl for the wild type. These results indicate that Arg 59 contributes to the thermodynamic stability of the Cam trimer. The R59K variant had k(cat) and k(cat)/K(m) values that were 8 and 5% of the wild-type values, respectively, while all other variants had k(cat) and k(cat)/K(m) values 10-100-fold lower than those of the wild type. The R59A, C, -E, -M, and -Q variants exhibited 4-63-fold increases in k(cat) and 9-120-fold increases in k(cat)/K(m) upon addition of 100 mM GdnHCl, with the largest increases observed for the R59A variant, which was comparable to the R59K variant. The kinetic results indicate that a positive charge at position 59 is essential for the CO(2) hydration step of the overall catalytic mechanism. PMID- 11781109 TI - Identification of active site residues involved in metal cofactor binding and stereospecific substrate recognition in Mammalian tyrosinase. Implications to the catalytic cycle. AB - Tyrosinase (Tyr) and tyrosinase-related proteins (Tyrps) 1 and 2 are the enzymes responsible for mammalian melanogenesis. They display high similarity but different substrate and reaction specificities. Loss-of-function mutations lead to several forms of albinism or other pigmentation disorders. They share two conserved metal binding sites (CuA and CuB) which, in Tyr, bind copper. To define some structural determinants for these differences, we mutated Tyr at selected residues on the basis of (i) conservation of the original residues in most tyrosinases, (ii) their nonconservative substitution in the Tyrps, and (iii) their possible involvement as an endogenous bridge between the copper pair. Two mutations at the CuA site, S192A and E193Q, did not affect Tyr activities, thus excluding S192 and E193 as endogenous ligands of the copper pair. Concerning CuB, the H390Q mutation completely abolished Tyr activity, whereas Q378H and H389L mutants showed 10-20% residual specific activities. Their kinetic behavior suggests that (i) H390 is the actual third ligand for CuB, (ii) H389 is critical for stereospecific recognition of o-diphenols but not monophenols, and (iii) the involvement in metal binding of the central extra H residue at the Tyrps CuB site is unlikely. However, replacement of Q (in Tyr) by H (in Tyrps) greatly diminished the affinity for L-dopa, consistent with the low/null tyrosinase activity of the Tyrps. These are the first data showing a physical difference in docking of mono- and o-diphenols to the Tyr active site, and they are used to propose a revised scheme of the catalytic cycle. PMID- 11781110 TI - Rates of oxygen and hydrogen exchange as indicators of TPQ cofactor orientation in amine oxidases. AB - This study presents the first detailed examination by resonance Raman (RR) spectroscopy of the rates of solvent exchange for the C5 and C3 positions of the TPQ cofactor in several wild-type copper-containing amine oxidases and mutants of the amine oxidase from Hansenula polymorpha (HPAO). On the basis of crystal structure analysis and differing rates of C5 [double bond] O and C3 [bond] H exchange within the enzyme systems, but equally rapid rates of C5 [double bond] O and C3 [bond] H exchange in a TPQ model compound, it is proposed that these data can be used to determine the TPQ cofactor orientation within the active site of the resting enzyme. A rapid rate of C5 [double bond] O exchange (t(1/2) < 30 min) and a slow (t(1/2) = 6 h) to nonexistent rate of C3 [bond] H exchange was observed for wild-type HPAO, the amine oxidase from Arthrobacter globiformis, pea seedling amine oxidase at pH 7.1, and the E406Q mutant of HPAO. This pattern is ascribed to a productive TPQ orientation, with the C5 [double bond] O near the substrate-binding site and the C3 [bond] H near the Cu. In contrast, a slow rate of C5 [double bond] O exchange (t(1/2) = 1.6-3.3 h) coupled with a fast rate of C3 [bond] H exchange (t(1/2) < 30 min) was observed for the D319E and D319N catalytic base mutants of HPAO and for PSAO at pH 4.6 (t(1/2) = 4.5 h for C5 [double bond] O exchange). This pattern identifies a flipped orientation, involving 180 degrees rotation about the C alpha-C beta bond, which locates the C3 [bond] H near the substrate-binding site and the C5 double bond] O near the Cu. Finally, fast rates of both C5 [double bond] O and C3 [bond] H exchange (t(1/2) < 30 min) were observed for the amine oxidase from Escherichia coli and the N404A mutant of HPAO, suggesting a mobile cofactor, with multiple TPQ orientations between productive and flipped. These results demonstrate that opposing sides of the TPQ ring possess different degrees of solvent accessibility and that the rates of C5 [double bond] O and C3 [bond] H exchange can be used to predict the TPQ cofactor orientation in the resting forms of these enzymes. PMID- 11781111 TI - On the birth of breast cancer. AB - Breast carcinoma is one of the most common neoplasms in women and is a leading cause of cancer related deaths worldwide. In recent years improved diagnostic tools have made it possible to detect breast cancers at early, even pre-invasive stages leading to a significant decrease in breast cancer mortality rates over the past decades. The increased number of patients diagnosed with pre-invasive breast tumors opened up new avenues in research and new dilemmas in clinical practice, since our understanding of the pathophysiology of such lesions is just beginning to emerge. Part of the delay and difficulty with analyzing pre-invasive tumors including ductal carcinoma in situ has been due to the lack of appropriate techniques suitable for studies of small, frequently microscopic size tumors. Recently developed technologies such as DNA microarrays and SAGE (serial analysis of gene expression) have made it possible to obtain comprehensive gene expression profiles of breast carcinomas of all stages. The application of these genomics approaches in combination with the complete sequence of the human genome and extensive molecular epidemiological studies is likely to further our understanding of the molecular basis of mammary tumorigenesis and will identify targets for risk prediction, cancer prevention and treatment. PMID- 11781112 TI - Epigenetics: unforeseen regulators in cancer. AB - The past several years have seen a tremendous advance in the understanding of the basic mechanisms of epigenetic regulation. A large number of studies have not only linked epigenetics with cell cycle regulation but also partially unravelled how epigenetics may regulate gene expression. The aim of this review is to provide an overview of the latest findings and current ideas on epigenetics with a focus on emphasizing the emerging influence epigenetics has on the onset and progression of cancer. PMID- 11781113 TI - Poly(ADP-ribose) polymerase: a guardian angel protecting the genome and suppressing tumorigenesis. AB - Poly(ADP-ribosyl)ation is an immediate cellular response to DNA damage generated either exogenously or endogenously. This post-translational modification is catalyzed by poly(ADP-ribose) polymerase (PARP, PARP-1, EC 2.4.2.30). It is proposed that this protein plays a multifunctional role in many cellular processes, including DNA repair, recombination, cell proliferation and death, as well as genomic stability. Chemical inhibitors of the enzyme, dominant negative or null mutations of PARP-1 cause a high degree of genomic instability in cells. Inhibition of PARP activity by chemical inhibitors renders mice or rats susceptible to carcinogenic agents in various tumor models, indicating a role for PARP-1 in suppressing tumorigenesis. Despite the above observations, PARP-1 knockout mice are generally not prone to the development of tumors. An enhanced tumor development was observed, however, when the PARP-1 null mutation was introduced into severely compromised immune-deficient mice (a mutation in DNA dependent protein kinase) or mice lacking other DNA repair or chromosomal guardian molecules, such as p53 or Ku80. These studies indicate that PARP-1 functions as a cofactor to suppress tumorigenesis via its role in stabilization of the genome, and/or by interacting with other DNA strand break-sensing molecules. Studies using PARP-1 mutants and chemical inhibitors have started to shed light on the role of this protein and of the specific protein post translational modification in the control of genomic stability and hence its involvement in cancer. PMID- 11781114 TI - Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. AB - Tumor cells often show a decrease in cell-cell and/or cell-matrix adhesion. An increasing body of evidence indicates that this reduction in cell adhesion correlates with tumor invasion and metastasis. Two main groups of adhesion molecules, cadherins and CAMs, have been implicated in tumor malignancy. However, the specific role that these proteins play in the context of tumor progression remains to be elucidated. In this review, we discuss recent data pointing to a causal relationship between the loss of cell adhesion molecules and tumor progression. In addition, the direct involvement of these molecules in specific signal transduction pathways will be considered, with particular emphasis on the alterations of such pathways in transformed cells. Finally, we review recent observations on the molecular mechanisms underlying metastatic dissemination. In many cases, spreading of tumor cells from the primary site to distant organs has been characterized as an active process involving the loss of cell-cell adhesion and gain of invasive properties. On the other hand, various examples of metastases exhibiting a relatively benign (i.e. not invasive) phenotype have been reported. Together with our recent results on a mouse tumor model, these findings indicate that 'passive' metastatic dissemination can occur, in particular as a consequence of impaired cell-matrix adhesion and of tumor tissue disaggregation. PMID- 11781115 TI - On not taking the world as you find it-epidemiology in its place. AB - Modern epidemiology has been criticized as being fragmented and reductionist, lacking coherent theories, and contributing little to the understanding of disease. These criticisms assume that epidemiology is a system of knowledge about health and disease, based on observation. In fact, consensus on the definition of the field is surprisingly elusive. A more practice-based approach would be to consider epidemiology as a field concerned with the methods for determining the causes of disease and for evaluating health services and treatments. The value of epidemiology is that it provides the tools for doing well-crafted research once the substantive hypothesis has been formulated. The focus of the discipline is thus methodological rather than conceptual. The major implication for the practitioner is that he or she must necessarily be more than an epidemiologist. Theoretical understanding must come from conceptual developments in the substantive fields of medicine, sociology, or biology and, more fundamentally, from fresh visions that transcend traditional categories of exposure and disease and accepted views of causation. PMID- 11781116 TI - Increased total mortality and cancer mortality in men with Dupuytren's disease: a 15-year follow-up study. AB - The aim of the present study was to evaluate the mortality rate and causes of death of individuals with Dupuytren's disease. In 1981/82, as part of The Reykjavik Study, a general health survey, 1297 males were examined for clinical signs of Dupuytren's disease. Based on the clinical evaluation the participants were classified into three groups: (1) those with no signs of Dupuytren's disease were referred to as the reference cohort; (2) those with palpable nodules in the palmar fascia were classified as having stage 1; and (3) those who had contracted fingers or had been operated on due to contractures were classified as having stage 2 of Dupuytren's disease. In 1997, after a 15- year follow-up period, the mortality rate and causes of death were investigated in relation to the clinical findings from 1981/82. Information about causes of death were obtained from the National Icelandic Death Registry and the Icelandic Cancer Registry. During the follow-up period, 21.5% (225/1048) of the reference cohort were deceased compared to 29.9% (55/184) of those with stage 1 and 47.7% (31/65) of those with stage 2 of Dupuytren's disease. When adjusted for age, smoking habits and other possible confounders, individuals with stage 2 of the disease showed increased total mortality [hazard ratio (HR) = 1.6; 95% CI 1.1-2.4]. Cancer deaths were increased (HR = 1.9; CI 1.0-3.6). In contrast, participants with stage 1 of Dupuytren's disease did not show increased mortality. A moderate but non-significant increase in cancer incidence was observed among individuals with stage 2 of Dupuytren's disease (HR = 1.5; 95% CI 0.9-2.4, P = 0.15). The study showed increased total mortality of individuals with Dupuytren's disease stage 2, where 42% of the excess in mortality could be attributed to cancer deaths. PMID- 11781117 TI - A novel approach to defining the relationship between lung function and symptom status in asthma. AB - We present a novel approach to estimating functional relationships between forced expiratory volume in 1 second (FEV(1)) and asthma-related symptoms on a population-wide basis. We used asthma-related clinical trials that reported estimates of mean lung function (measured as FEV(1) percent predicted) and symptoms (symptom score or percentage of symptom days or nighttime awakenings). Using average baseline values from each study in weighted linear regression analyses, we found a negative association between lung function and symptom score (P < 0.001) and the percentage of nighttime awakenings (P = 0.18), but no association between lung function and symptom days. We also found consistent relationships between the mean changes in lung function and symptoms at follow-up within the studies. Functional relationships between FEV(1) percent predicted and asthma-related symptoms can be useful for inferring the effect on the symptoms of a population associated with overall improvements in lung function. PMID- 11781118 TI - Comparison of metabolic risk profiles between subjects with fasting and 2-hour plasma glucose impairment: The Kinmen Study. AB - A two-step screening strategy was used to compare the metabolic risk profiles between subjects from Kinmen, Taiwan, who had fasting and 2-hr plasma glucose impairment and were considered at high risk of diabetes due to a fasting plasma glucose (FPG) between 5.6 and 7.8 mmol/l at the baseline screening. 1855 subjects without a previous diagnosis of diabetes who had an FPG of 5.6-7.8 mmol/l at the first step of screening were invited to undergo an Oral Glucose Tolerance Test (OGTT) for the second step of screening, and 1456 of these subjects (774 males and 682 females) completed the OGTT. Subjects who completed the OGTT were classified into normal, isolated impaired fasting glucose (isolated IFG), isolated impaired glucose tolerance (isolated IGT), both IFG and IGT, or undiagnosed diabetes groups. Sex-specific, age-adjusted mean values of metabolic risk profiles for various categories of glucose intolerance were calculated. The results for IFG and IGT agreed in only 20.8% of subjects. The clinical features of subjects with IGT (2-hr glucose impairment) were associated with cardiovascular risk profiles, while those subjects with isolated IFG (fasting glucose impairment only) were not. If the definition of IFG alone had been used for glucose intolerance screening, about 66.6% of subjects with IGT (i.e., isolated IGT with 2-hr glucose impairment and a normal fasting state) who had cardiovascular risk profiles would have been undetected. PMID- 11781119 TI - Risk tables for parkinsonism and Parkinson's disease. AB - We applied the incidence rates of parkinsonism and Parkinson's disease (PD) from Olmsted County, MN (1976-1990) to a hypothetical cohort undergoing the mortality rates observed in Minnesota, and computed the lifetime risk and the remaining lifetime risk of developing parkinsonism and PD. These risks were compared to cumulative incidences that do not take competing risks of death into account. The lifetime risk of developing parkinsonism from birth was 4.4% for men and 3.7% for women (ratio = 1.2). The corresponding risk of developing PD was 2.0% for men and 1.3% for women (ratio = 1.5). Because of the opposite effect of higher incidence and higher mortality rates in men, the lifetime risks were only slightly higher in men than in women. Lifetime cumulative incidences were consistently higher than lifetime risks; this difference was more pronounced in men and in older subjects. Lifetime risk estimates are useful in clinical practice, epidemiologic research, and public health. PMID- 11781120 TI - Development of a short osteoporosis quality of life questionnaire by equating items from two existing instruments. AB - This study aimed to develop a short Osteoporosis-Specific Quality of Life Questionnaire based on the assemblage (equating) of the items of two existing questionnaires (OQLQ and QUALEFFO). For this purpose, each questionnaire was administered by random assignment to a different group of female patients (OQLQ, n = 172; QUALEFFO, n = 166) with vertebral fractures due to osteoporosis. A common anchor test (SF-36) was also given to both groups. Seven different sets of OQLQ-QUALEFFO common items were defined by inspecting their own correlation with the scores of the eight dimensions of the SF-36. Within each set, equating consisted in connecting the OQLQ and QUALEFFO through their link with the SF-36. Equating was carried out through the Rasch mathematical model. Quantitative (item statistics) and qualitative reductions (expert opinion) of the equated sets resulted in a 16-item questionnaire. Although the new instrument requires further empirical validation, it provides a promising alternative to currently existing longer questionnaires for use in clinical practice. PMID- 11781121 TI - Features of excessive alcohol drinking in older adults distinctively captured by behavioral and biological screening instruments. An epidemiological study. AB - The entire > or =65-year-old population living in a small Italian town, where alcohol use is almost ubiquitous, was assessed with a frequency-quantity questionnaire for alcohol intake and with two screening instruments for alcohol problems, the CAGE questionnaire and the MCV-gammaGT test. Aim of the study was to assess whether these instruments identify different subsets of subjects with alcohol problems. Of the 649 participants, 19.1% were at-risk drinkers (average intake > 40 g/day in men and > 20 g/day in women). Both the screening instruments were positive in only a minority of participants. Of the 377 drinkers, 53 gave > or =1 affirmative response to the CAGE questionnaire, whereas 24 had a positive MCV-gammaGT test. The concordance between positive CAGE questionnaire and MCV gammaGT test was limited to seven subjects (kappa = 0.10), and these tests identified subjects who differed for several health and psychosocial characteristics. Participants aged > or =75 years drank less, but had similar prevalence of CAGE and MCV-gammaGT positive markers as compared to younger participants. In conclusion, excessive drinking is common in the elderly. Screening tests based on behavioral and biological markers identify two different sets of subjects with possible alcohol problems. This might indicate the opportunity to use these instruments in conjunction. PMID- 11781122 TI - Factors associated with self-reporting of chronic health problems in the French GAZEL cohort. AB - The objective of this study was to examine factors associated with self-reporting of chronic health problems. The self-reports were obtained from a questionnaire sent by mail to the French GAZEL cohort, composed of workers of a French company. The disorders reported in the questionnaire were compared with diagnoses from the sick-leave database of the company. Associations between self-reporting and characteristics were studied by multiple logistic regression analyses. Three types of characteristics were analyzed: individual, methodological and disorder related (i.e., prevalence of chronic disorders in the general population, probable disability and probable life risk scores). In 1992, the cohort consisted of 16,534 subjects aged 38 to 53 years. The reporting rate (number of self reports in the questionnaire divided by number of records in the sick-leave database for the disorder considered) varied from 8.9% to 100%. Self-reporting was associated with individual characteristics (gender, family status, place of residence, annual number of sick days and sick leaves), disorder-related characteristics (probable disability, prevalence) and methodological characteristics (precision of the formulation, delay between the last sick-day and the patient report). By body system, the characteristics associated with self reporting varied greatly but the annual number of sick days, probable disability and precision of formulation were the variables which remained most often in the models. These characteristics should be particularly taken into consideration in the interpretation of epidemiological results based on self-reporting. PMID- 11781123 TI - The influence of perceived well-being and reported symptoms on health care utilization: a population-based study. AB - The aim of this study was to evaluate the influence of reported well-being and symptoms on the utilization of health care, including alternative medicine. A random, age-stratified sample was drawn from the general population of Habo, a municipality in mid-Sweden. Of the 1312 subjects sampled, 827 responded to a postal questionnaire, providing information on health care utilization during the previous year, on a number of well-being variables and on perceived symptoms during the past 3 months. Subjects who reported low scores for perceived health and sleep had significantly more appointments with a physician than subjects reporting high scores. These results remained when the influence of age, sex, marital status, household size, educational level, occupational status and presence of chronic disease, shown to affect health care utilization in a previous report, was taken into account. In addition, multi-symptom reporters had higher odds for appointments with physicians or providers of alternative medicine than those with few symptoms when account was taken of potential confounders. The effect of perceived health was independent of symptom reporting on health care utilization, indicating that there is probably no simple chain of causation involved. Health care consumption, especially out-patient care, appears to be linked to perceived bad health and the multi-symptom reporting, factors that together with other known predictors perhaps might be used to estimate future health care needs. PMID- 11781124 TI - Reliability and validity of comprehensive health status measures in children: The Child Health Questionnaire in relation to the Health Utilities Index. AB - This study assesses the feasibility, reliability and validity of the Child Health Questionnaire-Parent Form (CHQ-PF50), consisting of 11 multi-item scales covering the physical, emotional and social well-being of children. The Health Utilities Index mark 2 (HUI2) was selected for comparison. Parents of 467 Dutch schoolchildren (age 5-13) were sent CHQ and HUI questionnaires. A subgroup of 79 parents of children aged 10-11 were sent a retest after 2 weeks. Feasibility: 78% response with few missing/non-unique CHQ-answers (<1%). Internal consistency: Cronbach's alphas of.39-.96 (mean.72). Item-own scale correlations were higher than item-other scale correlations. Test-retest ICCs were statistically significant for all but two CHQ scales (ICCs.31-.84). Test-retest CHQ-scale means did not show statistically significant differences except for one scale ("Behavior"). VALIDITY: the CHQ-scales, with one exception, correlated better with predefined parallel HUI domains (ICCs.26-.53), than with non-parallel domains. Six CHQ scales discriminated clearly between children with and without chronic conditions and three scales discriminated between high and low medical consumption. This was at least equivalent to the discriminative ability of the HUI2 in this study. Additional studies of test-retest reliability and responsiveness to change of the CHQ in varied populations are needed. From the present study and literature data on other (clinical) populations we conclude that psychometric properties of CHQ-based health status measurement justify application in pediatric outcome studies, in addition to clinical measures. PMID- 11781125 TI - Should systematic reviews include non-randomized and uncontrolled studies? The case of acupuncture for chronic headache. AB - We aimed to investigate: (1) whether patient and intervention characteristics, design-independent quality aspects, and response rates differ between randomized and non-randomized trials of acupuncture for chronic headache; (2) whether non randomized studies provide useful additional information (regarding long-term effects, prognostic factors, adverse effects, and generalizability); (3) reasons for potential differences in response rates. Studies including at least five patients and reporting clinical outcome data were identified through searches in Medline, Embase, the Cochrane Controlled Trials Register, other databases and checking of bibliographies. Twenty-four randomized trials and 35 non-randomized studies (five non-randomized controlled cohort studies, 10 prospective uncontrolled studies, 10 case series, and 10 cross-sectional surveys) met the inclusion criteria. Studies were heterogeneous regarding patients, interventions, outcome measurements and results. On average, randomized trials had smaller sample sizes, met more quality criteria, and had lower response rates (0.59 [95% confidence interval 0.48-0.69] vs. 0.78 [0.72-0.83]). Whether randomized or not, studies meeting more quality criteria had lower response rates. Non-randomized studies did not have significantly longer follow-up periods, three included an analysis of prognostic variables, only one reported on adverse effects, and the degree of generalizability was unclear. In the case of acupuncture for chronic headache, non-randomized studies confirmed the finding of a systematic review of randomized trials that the treatment is likely to be effective but provided little relevant additional information on long-term effects, prognostic factors, and adverse effects. PMID- 11781126 TI - A comparison of summary patient-level covariates in meta-regression with individual patient data meta-analysis. AB - OBJECTIVES: To compare meta-analysis of summary study level data with the equivalent individual patient data (IPD) analysis when interest lies in identification of binary patient characteristics related to treatment efficacy. DESIGN: A simulation study comparing meta-regression with IPD analyses of randomized controlled trials. METHODS: Twenty-seven different meta-analysis situations were simulated with 1000 repetitions in each case. The following parameters were varied: (1) the treatment effect magnitude for different patient risk groups; (2) sample sizes of individual studies; and (3) number of studies. The meta-regression and IPD results were then compared for each situation. RESULTS: The statistical power of meta-regression was dramatically and consistently lower than that of IPD analysis, with little agreement between the parameter estimates obtained from the two methods. Only in meta-analyses of large numbers of large trials, did meta-regression detect differential treatment effects between risk groups with any consistency. CONCLUSIONS: Meta-analysis of summary data may be adequate when estimating a single pooled treatment effect or investigating study level characteristics. However, when interest lies in investigating whether patient characteristics are related to treatment, IPD analysis will generally be necessary to discover any such relationships. In these situations practitioners should try to obtain individual-level data. PMID- 11781127 TI - Utilization of lipid-lowering drugs in men and women. a reflection of the research evidence? AB - This study analyzes the utilization of statin lipid-lowering drugs in a Canadian province using a population-wide drug prescription database. The utilization pattern is compared to the results of a systematic review of randomized controlled trials on their effectiveness. The study found that 74.7% of individuals prescribed a statin had no reported history of coronary heart disease (CHD). Women without CHD formed 23.1% of statins recipients; 32.9% of individuals filling a statin prescription were age 70 and over. Only 15.3% of men with CHD had been prescribed a statin. Based on the systematic review, 88.7% of the utilization of statins in this Canadian province was not supported by the results of the systematic review. Considering baseline lipid-levels does not substantially alter these findings. This study concludes that statins prescribing practices need to be realigned with research evidence. This implies refocusing utilization away from women and the elderly, towards men with CHD. PMID- 11781128 TI - The number needed to treat is value-laden. PMID- 11781130 TI - Statistical comments on a re-analysis of a previous meta-analysis of homeopathic RCTs. PMID- 11781132 TI - Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis. AB - Caveolae, the flask-shaped membrane invaginations abundant in endothelial cells, have acquired a prominent role in signal transduction. Evidence, that events occurring in caveolae participate in cell survival and angiogenesis, has been recently substantiated by the identification of two novel caveolar constituents: prostacyclin synthase (PGIS) and the cellular form of prion protein (PrP(c)). We have shown that PGIS, previously described as an endoplasmic reticulum component, is bound to caveolin-1 (cav-1) and localized in caveolae in human endothelial cells. By generating prostacyclin, PGIS is involved in angiogenesis. Previous observations regarding the localization of PrP(c) in caveolae-like membrane domains (CLDs) have been recently confirmed and extended. It has been demonstrated that PrP(c) is bound to cav-1 and, by recruiting Fyn kinase, can participate in signal transduction events connected to cell survival and differentiation. The new entries of PGIS and PrP(c) in caveolar components place caveolae and CLDs at the centre of a network, where cells decide whether to proliferate or differentiate and whether to survive or to suicide by apoptosis. PMID- 11781133 TI - Adenosine receptors: G protein-mediated signalling and the role of accessory proteins. AB - Ever since the discovery of the effects of adenosine in the circulation, adenosine receptors continue to represent a promising drug target. Firstly, this is due to the fact that the receptors are expressed in a large variety of cells; in particular, the actions of adenosine (or, respectively, of the antagonistic methylxanthines) in the central nervous system, in the circulation, on immune cells and on other tissues can be beneficial in certain disorders. Secondly, there exists a large number of ligands, which have been generated by introducing several modifications in the structure of the lead compounds (adenosine and methylxanthine), some of them highly specific. Four adenosine receptor subtypes have been identified by molecular cloning; they belong to the family of G protein coupled receptors, which transfer signals by activating heterotrimeric G proteins. It has been appreciated recently that accessory proteins impinge on the receptor/G protein interaction and thus modulate the signalling reaction. These accessory components may be thought as adaptors that redirect the signalling pathway to elicit a cell-specific response. Here, we review the recent literature on adenosine receptors and place a focus on the role of accessory proteins in the organisation of adenosine receptor signalling. These components have been involved in receptor sorting, in the control of signal amplification and in the temporal regulation of receptor activity, while the existence of others is postulated on the basis of atypical cellular reactions elicited by receptor activation. PMID- 11781134 TI - Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists. AB - Inhibitors of intracellular signalling events, including enzyme inhibitors, are often used to investigate signal transduction pathways. We examined whether some inhibitors that act on the ATP site of enzymes are also potent adenosine receptor antagonists. Competitive radioligand binding assays in membranes or brain sections show that genistein, chelerythrine, and SQ22536 [9-(tetrahydro-2'-furyl) adenine] block A(1), A(2A), and A(3) adenosine receptors in concentrations of these drugs commonly used to examine cellular signalling (K(i) of [(3)H]-DPCPX (1,3-dipropyl-8-cyclopentylxanthine) competition mean (95% confidence interval): 2.6 (1.5-4.8) microM, 5.7 (2.1-15.8) microM, 59.4 (17.3-203.8) microM; K(i) of [(3)H]-SCH58261 [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4 triazolo[1,5-c]pyrimidine] competition: 15.3 (8.1-28.8) microM, 37.6 (10.3-137.4) microM, 16.7 (11.5-24.3) microM for genistein, chelerythrine, and SQ22536, respectively). Given that adenosine receptors are present on most cells, that adenosine is often present, and that adenosine receptors interact functionally with several signalling pathways, these results may be of significance also when studying signalling via other receptors. PMID- 11781135 TI - Activation of Erk1/Erk2 and transiently increased p53 levels together may account for p21 expression associated with phorbol ester-induced transient growth inhibition in HepG2 cells. AB - In HepG2 cells grown in the presence of serum, enhanced Raf-activation correlated with transient growth inhibition. The activation of Raf was increased either by the phorbol ester-induced activation of protein kinase C (PKC) or by the addition of the PKC inhibitor bisindolylmaleimide I (BIM). Either of these treatments increased the cellular levels of p21 by an Erk1/Erk2 MAP kinase cascade-dependent way, since this increase was prevented by the MEK-inhibitor PD98059. Nevertheless, the growth inhibition correlated with the transient increase of p53 levels as well. Either the activation of PKC with phorbol ester or the addition of BIM to cells growing in serum induced a rapid but transient increase of p53 levels, which preceded growth inhibition. This increase of p53 levels was probably due to the transient stabilisation of p53 and did not require the activation of Erk1/Erk2. PMID- 11781136 TI - Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis. AB - Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) kinases (MEKKs) are serine/threonine kinases that are upstream regulators of MAPKs. Here, the role of the amino-terminal (N-terminal) domain of MEKK1-4 on the regulation of different intracellular signaling pathways, apoptosis, and cell proliferation has been assessed by comparing the responses induced by the full-length (FL) MEKKs to those induced by the kinase domains only. For each MEKK, the pattern of activation of NF kappa B, the ERK MAPK pathway, and the c-Jun N-terminal kinase (JNK) MAPK pathway markedly differed between the kinase domain and the FL form. Similarly, cell proliferation and apoptosis were differently regulated by the FL MEKK and the corresponding kinase domain. Our data show that the N-terminal domain of the MEKKs determines the specificity and the strength of activation of various intracellular signaling pathways and cellular responses. PMID- 11781137 TI - Calcium-dependent activation of Pyk2 by hypoxia. AB - The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID- 11781138 TI - Reciprocal mutations of highly conserved residues in transmembrane helices 2 and 7 of the alpha(2A)-adrenoceptor restore agonist activation of G(i1)alpha. AB - Fusion proteins were constructed between the alpha(2A)-adrenoceptor and the alpha subunit of the G-protein G(i1). Mutation of the highly conserved Asp(79) in transmembrane (TM) helix 2 of the receptor to Asn reduced the capacity of agonists to activate G(i1)alpha by 95% without altering [3H]antagonist or agonist ligand-binding affinity. A reciprocal mutation in TM helix 7 (Asn(422)Asp) was without effect on signalling effectiveness. Combination of these two mutations overcame the effect of the Asp(79)Asp mutation. By examining alterations in this helix 2-helix 7 microdomain, we further demonstrate the utility of receptor-G protein fusion proteins to quantitate mutational effects on receptor-G-protein interactions and information transfer. PMID- 11781139 TI - Human macrophage adhesion on fibronectin: the role of substratum and intracellular signalling kinases. AB - Fibronectin and Arg-Gly-Asp (RGD)- and/or Pro-His-Ser-Arg-Asn (PHSRN)-containing oligopeptides were immobilized onto physicochemically distinct substrata: polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role of selected signalling kinases in the adhesion of human primary blood-derived macrophages on these modified substrata was investigated. We demonstrated that the protein tyrosine kinase (PTK) or protein serine/threonine kinase (PSK) dependency and the PTK-PSK cross-talk compensation for macrophage adhesion varied dynamically with the substratum modification and the culture time. The inhibition of MAPK kinase (MAPKK) decreased macrophage adhesion on TCPS, whereas the inhibition of phosphoinositide-3 kinase (PI3 kinase) decreased macrophage adhesion on networks at 24 h. The PI3 kinase-protein kinase C (PKC)-MAPK cascade was involved in macrophage adhesion on fibronectin-preadsorbed TCPS or networks but not on fibronectin-grafted networks. This fibronectin-mediated adhesion signalling involved both RGD and PHSRN sequences in a form of G(3)RGDG(6)PHSRNG on TCPS but not on networks. Furthermore, G(3)RGDG(6)PHSRNG grafted onto networks evoked unique signalling in macrophage adhesion from that preadsorbed onto networks. Thus, macrophage adhesion and the role of selected signalling kinases were modulated by the substratum and the ligand conjugation method. PMID- 11781140 TI - XOD-catalyzed ROS generation mobilizes calcium from intracellular stores in mouse pancreatic acinar cells. AB - In fura-2 loaded isolated mouse pancreatic acinar cells, xanthine oxidase (XOD) catalyzed reactive oxygen species (ROS) generation caused an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) by release of Ca(2+) from intracellular stores. The ROS-induced Ca(2+) signals showed large variability in shape and time-course and resembled in part Ca(2+) signals in response to physiological secretagogues. ROS-induced Ca(2+) mobilization started at the luminal cell pole and spread towards the basolateral side in a wave manner. ROS evoked Ca(2+) responses were not inhibited by the phospholipase C (PLC) inhibitor U73122 (10 microM). Neither 2-aminoethoxy-diphenylborate (2-APB) (70 microM) nor ryanodine (50 microM) suppressed ROS-evoked Ca(2+) release. ROS still released Ca(2+) when the endoplasmic reticulum Ca(2+)-ATPase was blocked with thapsigargin (1 microM), or when rotenone (10 microM) was added to release Ca(2+) from mitochondria. Our results suggest that pancreatic acinar cells ROS do not unspecifically affect Ca(2+) homeostasis. ROS primarily affect Ca(2+) stores located in the luminal cell pole, which is also the trigger zone for agonist induced Ca(2+) signals. Release of Ca(2+) induces Ca(2+) waves carried by Ca(2+) induced Ca(2+) release and produces thereby global Ca(2+) signals. Under oxidative stress conditions, the increase in [Ca(2+)](i) could be one mechanism contributing to an overstimulation of the cell which could result in cell dysfunction and cell damage. PMID- 11781141 TI - CaMKII is activated and translocated to the secretory apical membrane during cholinergically conveyed gastric acid secretion. AB - The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is thought to be activated during the cholinergic stimulation of gastric acid secretion. The carbachol-induced acid production of cultured rabbit parietal cells was dose dependently inhibited by the CaMKII inhibitor KN-62 as measured by accumulation of the weak base [(14)C]aminopyrine ([(14)C]-AP). Inhibition by KN-62 was most efficient at concentrations of carbachol >10(-6) M. After carbachol stimulation, we observed an activation of CaMKII activity, and its translocation to the apical membrane of gastric mucosal cells. We found a doubling of the abundance of CaMKII to the stimulus-associated apical membrane (SA vesicles) compared to the apical membrane from the resting state after carbachol induction. This was shown by both an anti-CaMKII serum and the 1.8-fold increase of the CaMKII phosphotransferase activity in vitro. The SA vesicles exhibited a strong increase of autoactivated CaMKII probed with an anti-autoactivated CaMKII antibody. Additionally, we observed a colocalization of both CaMKII and the H(+)-K(+)-ATPase of SA vesicles similar to the colocalization of both enzymes to the tubulovesicles suggesting them as at least one pool for the SA vesicular CaMKII. Our data indicate that the activation of CaMKII and the carbachol-dependent redistribution of CaMKII to the SA vesicles are distinct processes that occur in parallel to regulate the activity and localization of CaMKII. These findings contribute to the model implicating an involvement for CaMKII in the intracellular dynamics of the acid secretion. PMID- 11781142 TI - Regulation of phospholipase C-gamma 2 via phosphatidylinositol 3-kinase in macrophages. AB - Phospholipase C-gamma (PLC-gamma) isoforms are thought to be activated by both tyrosine phosphorylation and phosphatidylinositol 3,4,5 trisphosphate (PtdIns 3,4,5 P(3)), the product of phosphatidylinositol 3-kinase (PtdIns 3-kinase). In this study, we show that stimulation of mouse macrophages with either zymosan beads or bacteria (Prevotella intermedia) induced tyrosine phosphorylation of PLC gamma 2. Zymosan stimulation also induced translocation to membrane and cytoskeleton fractions, which was inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY 294002. However, the tyrosine phosphorylation of PLC-gamma 2 induced by zymosan was not affected by the inhibitors wortmannin and LY 294002. In contrast to zymosan and bacteria, PLC-gamma 2 was not phosphorylated by stimulation with lipopolysaccharide (LPS), phorbol ester or calcium ionophore. Moreover, the PLC-gamma 1 isoform was not detected in mouse macrophages. These data indicate that PtdIns 3-kinase is critical for the translocation but not for the tyrosine phosphorylation of PLC-gamma 2 in mouse macrophages and that the latter may be insufficient for enzyme activation. PMID- 11781143 TI - Ser-474 is the major target of insulin-mediated phosphorylation of protein kinase B beta in primary rat adipocytes. AB - The mechanism of activation for protein kinase B (PKB), an important target for insulin signaling, has been scarcely investigated in primary cells. In this study, we have characterized the insulin-induced phosphorylation and activation of PKB beta in primary rat adipocytes. Insulin stimulation resulted in a translocation of PKB beta from cytosol to membranes, and phosphorylation and activation of PKB beta. Phosphoamino acid analysis and phosphopeptide mapping demonstrated that the phosphorylation occurred mainly on serines, also when using calyculin A, and that these were localized within one major phosphopeptide. Radiosequencing showed that the radioactivity was released in Cycle No. 7. In addition, the peptide was specifically immunoprecipitated from a tryptic digest of PKB beta using the anti-phospho-PKB (Ser-473) antibody. Taken together, these results show that rat adipocyte PKB beta mainly is phosphorylated on Ser-474 in response to insulin stimulation, in contrast to previous studies in human embryonic kidney (HEK) 293 cells demonstrating, in addition, phosphorylation of Thr-309. PMID- 11781144 TI - Human alpha-fetoprotein as a Zn(2+)-binding protein. Tight cation binding is not accompanied by global changes in protein structure and stability. AB - The binding of zinc to human alpha-fetoprotein (AFP) isolated from human umbilical cord serum was studied by fluorimetric Zn(2+)-titration. We found that the total number of strong binding sites for zinc on this protein was 5: AFP has one very strong (dissociation constant, K(d)<10(-8) M) and at least four lower affinity zinc binding sites (K(d)<10(-5) M). Fourier transform infrared (FTIR) analysis revealed that aspartate and histidine residues could be involved in the strong coordination of zinc. Intriguingly, binding of zinc to the protein does not induce structural changes that can be detected by circular dichroism, FTIR, intrinsic fluorescence or (1,1')-bi-(4-anilino)naphthalene-5,5'-disulfonic acid (bis-ANS) binding. Finally, scanning microcalorimetry measurements showed that stability of the protein is also unaffected by zinc binding in spite of the strength of the coordination. Such strong interactions without major structural consequences are highly unusual, and AFP may therefore be the first characterized representative of a new class of ligand-binding proteins. PMID- 11781145 TI - The inhibitory effects of immunosuppressive factors, dexamethasone and interleukin-4, on NF-kappaB-mediated protease production by oral cancer. AB - Matrix metalloproteinase-9 (MMP-9) produced by tumor cells is known to be implicated in the invasion of squamous cell carcinoma (SCC). In the process of searching for agents to inhibit MMP-9 in cancer, immunosuppressive factors, dexamethasone (DEX) and interleukin-4 (IL-4) were found to inhibit protein production as well as gene expression of MMP-9 in tumor necrosis factor alpha (TNFalpha)-stimulated SCC cells. DEX and IL-4 could also suppress the expression of urokinase type plasminogen activator (uPA) to prevent the conversion from the proenzyme form of MMP-9 to its active form. Regarding their mechanisms to inhibit the expression of MMP-9 and uPA, DEX and IL-4 had no effect on the cell surface levels of TNFalpha receptors, but inhibited the activation of NF-kappaB and NF kappaB-dependent gene expression. DEX, but not IL-4, could strongly augment the TNFalpha-induced expression of IkappaBalpha in SCC cells. These results suggest that DEX and IL-4 suppress not only immunological reactions, but also tumor invasion by targeting NF-kappaB. PMID- 11781146 TI - Metabolic consequence of long-term exposure of pancreatic beta cells to free fatty acid with special reference to glucose insensitivity. AB - Long-term exposure of the pancreatic beta cells to free fatty acid (FFA) reportedly inhibits glucose-stimulated insulin secretion. We here studied the impact of FFA on glucose and lipid metabolism in pancreatic beta cells with special reference to insulin secretion. Pancreatic beta-cell line MIN6 was exposed to various concentrations of palmitate for 3 days. Glucose-stimulated insulin secretion and insulin content were decreased corresponding to the concentration of the palmitate exposed. Glycolytic flux and ATP synthesis was unchanged, but pyruvate-stimulated change in NAD(P)H concentration was decreased. Pyruvate carboxylase was decreased at the protein level, which was restored by the removal of palmitate or the inhibition of beta-oxidation. Intracellular content of triglyceride and FFA were elevated, beta-oxidation was increased, and de novo lipogenesis from glucose was decreased. NADPH content and citrate output into the medium, which reflected pyruvate malate shuttle flux, were decreased, but malic enzyme activity was unaffected. The malic enzyme inhibitor alone inhibited insulin response to glucose. In conclusion, long-term exposure of FFA to beta cells inhibits glucose-stimulated insulin secretion via the decreased NADPH contents due to the inhibition of pyruvate carboxylase and malate pyruvate shuttle flux. PMID- 11781147 TI - Characterization of a missense mutation at histidine-44 in a pyruvate dehydrogenase-deficient patient. AB - Genetic defects in pyruvate dehydrogenase complex (PDC) cause lactic acidosis, neurological deficits, and often early death. Most mutations of PDC are localized in the alpha subunit of the pyruvate dehydrogenase (E1) component. We have kinetically characterized a patient's missense mutation alphaH44R in E1alpha by creating and purifying three recombinant human E1s (alphaH44R, alphaH44Q, and alphaH44A). Substitutions at histidine-15 resulted in decreased V(max) values (6% alphaH44R; 30% alphaH44Q; 90% alphaH44A) while increasing K(m) values for thiamine pyrophosphate (TPP) compared to wild-type (alphaH44R, 3-fold; alphaH44Q, 7-fold; alphaH44A, 10-fold). This suggests that the volume of the residue at site 15 is important for TPP binding and substitution by a residue with a longer side chain disrupts the active site more than the TPP binding site. The rates of phosphorylation and dephosphorylation of alphaH44R E1 by E1-kinase and phospho-E1 phosphatase, respectively, were similar to that of the wild-type E1 protein. These results provide a biochemical basis for altered E1 function in the alphaH44R E1 patient. PMID- 11781148 TI - A novel splicing mutation causes an undescribed type of analbuminemia. AB - Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous subjects. In this report we describe a new molecular defect that caused the analbuminemic trait in a newborn of Iraqi origin. When the parents' DNA was analyzed, both subjects were found to be heterozygous for the same mutation found in the infant. All the 14 exon and flanking intron sequences of the albumin gene were amplified via PCR and screened for mutations by SSCP and heteroduplex analysis. A mutation in the DNA region encoding exon 1 and its flanking intron was revealed by the presence of a heteroduplex. The fragment, which was directly DNA sequenced, contains a previously unreported single nucleotide change, consisting in a G to A substitution at nucleotide 118 in the structural gene of the human protein. This mutation, involving the first base of intron 1, destroys the GT dinucleotide consensus sequence found at the 5' end of most intervening sequences and causes the defective pre-mRNA splicing responsible for the analbuminemic trait. PMID- 11781149 TI - Presence of BRCA1 and BRCA2 proteins in human milk fat globules after delivery. AB - We evaluated BRCA1 and BRCA2 oncosuppressor protein expression in 26 milk samples in women just after delivery. The quantification of BRCA1 and BRCA2 proteins was performed in isolated milk fat globules using an affinity chromatography strategy. The amounts of BRCA1 and BRCA2 proteins were found to be similar. We explained the presence of BRCA1 and BRCA2 proteins in human milk fat globules by the fact that they are formed by exocytosis of lipids from epithelial cells of the mammary gland and are enveloped by plasma membrane from the apical part of the milk-secreting cells. This raises the possibility that BRCA1 and BRCA2 proteins are a protective response to proliferation and play a possible role in newborn nutrition. PMID- 11781150 TI - Effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts: (87)Rb MRI and (31)P MR spectroscopic study. AB - The study compared the effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts perfused by the Langendorff method. The left anterior descending artery (LAD) was cannulated and the LAD bed was perfused with the same specific flow as the whole heart. Following equilibration with normal Krebs-Henseleit buffer (KHB, pO(2) 568 mm Hg, pH 7.42) the perfusate was switched to one that contained Rb(+) (Rb-KHB). Simultaneously, perfusion through the LAD was carried out with hypoxic (pO(2)=31 mm Hg), an acidemic (pH 7.12) or normal (pO(2)=550 mm Hg) Rb-KHB for 120 min. (87)Rb images of the entire heart or localized (31)P spectra from the left ventricular anterior wall were acquired. Hypoxia decreased the maximal (87)Rb image intensity and Rb(+) flux in the anterior wall to 79+/-9% and 85+/-7%, respectively, of that in the posterior wall. Extracellular acidosis did not affect (87)Rb image intensity and reduced Rb(+) flux (83+/-10%). During hypoxia phosphocreatine and ATP decreased to 36+/ 10 and 50+/-15% of baseline, respectively and intracellular pH (pHi) decreased to 6.90+/-0.05. Extracellular acidosis did not affect the phosphocreatine or ATP levels but reduced pHi (7.06+/-0.18 vs. 7.26+/-0.06 in control). We suggest that intracellular acidosis plays a role in the inhibition of Rb(+) uptake during hypoxia. PMID- 11781151 TI - Renal function and cortical (Na(+)+K(+))-ATPase activity, abundance and distribution after ischaemia-reperfusion in rats. AB - The effects of ischaemic injury and reperfusion on renal function, cortical ATP content, alkaline phosphatase activity and (Na(+)+K(+))-ATPase activity and abundance in cortical homogenates and isolated basolateral and apical membranes were examined. Rats were submitted to 5 or 40 min of right renal artery occlusion and 60 min of reperfusion. Renal function of the ischaemic-reperfused kidney was studied by conventional clearance techniques. Our results show that 1 h of reperfusion after a short period of renal ischaemia (5 min) allows the complete restoration of the biochemical features of cortical cells and functional properties of the injured kidney. A longer period of ischaemia, such as 40 min, followed by 1 h of reperfusion showed functional and biochemical alterations. ATP recovered from 26% after 40 min of ischaemia to 50% of control values after 1 h reperfusion. However, renal function was strongly impaired. Brush border integrity was compromised, as suggested by AP excretion and actin appearance in urine. Although total cortical (Na(+)+K(+))-ATPase activity was not different from controls, its distribution in isolated apical and basolateral membranes was abnormal. Remarkably, we detected an increase in alpha-subunit protein abundance that may suggest that (Na(+)+K(+))-ATPase synthesis is promoted by ischaemia reperfusion. This increase may play an important role in the pathophysiology of ischaemic acute renal failure. PMID- 11781152 TI - Inhibition of cytochrome c oxidase activity in rat cerebral cortex and human skeletal muscle by D-2-hydroxyglutaric acid in vitro. AB - L-2-Hydroxyglutaric (LGA) and D-2-hydroxyglutaric (DGA) acids are the characteristic metabolites accumulating in the neurometabolic disorders known as L-2-hydroxyglutaric aciduria and D-2-hydroxyglutaric aciduria, respectively. Although these disorders are predominantly characterized by severe neurological symptoms, the neurotoxic mechanisms of brain damage are virtually unknown. In this study we have evaluated the role of LGA and DGA at concentrations ranging from 0.01 to 5.0 mM on various parameters of energy metabolism in cerebral cortex slices and homogenates of 30-day-old Wistar rats, namely glucose uptake, CO(2) production and the respiratory chain enzyme activities of complexes I to IV. DGA significantly decreased glucose utilization (2.5 and 5.0 mM) by brain homogenates and CO(2) production (5 mM) by brain homogenates and slices, whereas LGA had no effect on either measurement. Furthermore, DGA significantly inhibited cytochrome c oxidase activity (complex IV) (EC 1.9.3.1) in a dose-dependent manner (35-95%) at doses as low as 0.5 mM, without compromising the other respiratory chain enzyme activities. In contrast, LGA did not interfere with these activities. Our results suggest that the strong inhibition of cytochrome c oxidase activity by increased levels of DGA could be related to the neurodegeneration of patients affected by D-2-hydroxyglutaric aciduria. PMID- 11781153 TI - Changes in gene expression in rat thymocytes identified by cDNA array support the occurrence of oxidative stress in early magnesium deficiency. AB - Magnesium deficiency in experimental animals leads to inflammation, exacerbated immune stress response and a decrease of specific immune response. It also results in a significant increase in free radical species and subsequent tissue injury. An accelerated thymus involution was observed in Mg-deficient rats in relation to enhanced apoptosis and enhanced susceptibility to oxidative stress. To examine the stress-inducing effects of low Mg status on thymocytes, cDNA arrays were used to evaluate changes in gene expression in weaning rats submitted to Mg deficiency of short duration (2 days). Several genes exhibited changes in their expression caused by Mg deficiency before any perceptible modification in cell integrity and functions. The up-regulated genes included cytochrome c oxidase, glutathione transferase, CuZn superoxide dismutase, genes associated with the stress response (HSP70 and HSP84) and a gene involved in DNA synthesis and repair (GADD45). The down-regulated genes included Na/P cotransporter 1. These findings are consistent with altered cell growth, modifications of ion fluxes and oxidative stress described during Mg deficiency. The observation of induction of genes involved in protection and repair in cells from Mg-deficient animals provides additional evidence of the role of oxidative stress in the pathobiology of this deficiency. PMID- 11781154 TI - X Chromosomal short tandem repeat polymorphisms near the phosphoglycerate kinase gene in men with chronic prostatitis. AB - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) causes substantial morbidity afflicting approximately 10% of adult males. Treatment is often empirical and ineffective since the etiology is unknown. Other prostate and genitourinary diseases have genetic components suggesting that CP/CPPS may also be influenced by genetic predisposition. We recently reported a highly polymorphic short tandem repeat (STR) locus near the phosphoglycerate kinase gene within Xq11-13. Because this STR is in a region known to predispose towards other prostate diseases, we compared STR polymorphisms in 120 CP/CPPS patients and 300 control blood donors. Nine distinct allele sizes were detected, ranging from 8 to 15 repeats of the tetrameric STR plus a mutant allele (9.5) with a six base deletion in the flanking DNA sequence. The overall allele size distribution in the CP/CPPS patients differed from controls (Chi-square=19.252, df=8, P=0.0231). Frequencies of two specific alleles, 9.5 and 15, differed significantly in CP/CPPS vs. control subjects and allele 10 differed with marginal significance. Alleles 9.5 and 10 were both more common in CP/CPPS patients than controls while allele 15 was less common. These observations suggest that Xq11-13 may contain one or more genetic loci that predispose toward CP/CPPS. Further investigations involving family studies, larger patient populations, and other control groups may help elucidate this potential genetic predisposition in CP/CPPS. PMID- 11781155 TI - Systemic lupus erythematosus patients under immunosuppressive treatment express high levels of the immunoglobulin lambda variable IGLV8S1 gene with silent somatic mutations. AB - Systemic lupus erythematosus (SLE) patients express high titers of somatically mutated serum autoantibodies against nuclear structures including double-stranded DNA. These somatic mutations accumulate codons for basic amino acids in the immunoglobulin variable regions of both, heavy and light chains, facilitating binding to nucleic acids. The variable (V) immunoglobulin lambda 8 (IGLV8S1) gene contributes to autoreactive B-cell repertoire of auto-immune patients. Accumulation of immune complexes of these anti-DNA autoantibodies causes severe systemic inflammation in SLE. The current treatment of lupus disease is based on immunosuppressive drugs, but the precise role for this therapy remains to be defined. To evaluate the in vivo effect of combined immunosuppressive treatment on B-lymphocytes repertoire of SLE patients, we have developed an approach using the IGLV8S1 gene as a marker. The transcription of this gene in treated SLE patients was increased. However, we observed a trend, in these patients, to conserve complementarity determining regions (CDRs) and framework regions (FRs) of Vlambda8 polypeptide light chain deduced sequence, from its germline counterpart. Sequencing IGLV8S1 cDNA of untreated SLE patients, taken as a control for treatment effect, displayed a decreased frequency of silent somatic mutations (consequently high frequency of replacement mutations) in the Vlambda8 polypeptide chain deduced sequence. These data suggest that the immunosuppressive drug treatment modulates the positive selection of somatically mutated Vlambda8 light chain. PMID- 11781156 TI - P24, a glycogen synthase kinase 3 (GSK 3) inhibitor. AB - A heat resistant glycogen synthase kinase 3 (GSK 3) binding protein, p24, that inhibits its kinase activity at a low magnesium concentration (in a way similar to that of lithium) was found in microtubules from adult rat brains. This protein associates with GSK 3 in microtubules and corresponds to one previously described in the literature as p25, although it has a relative molecular weight of 23472. p24 is a poor substrate for GSK 3 but it could be phosphorylated by other protein kinases such as cAMP dependent protein kinase and cdk 5. Since p24 could form complexes with GSK 3, it may not only regulate GSK 3 activity but also it might act as an anchoring protein for the kinase. PMID- 11781157 TI - Sialyltransferase activity of human plasma and aortic intima is enhanced in atherosclerosis. AB - Sialyltransferase activity has been determined in membrane preparations containing the Golgi apparatus that were isolated from atherosclerotic and normal human aortic intima as well as in plasma of patients with documented atherosclerosis and healthy donors by measuring the transfer of N acetylneuraminic acid (NeuAc) from CMP-NeuAc to asialofetuin. The asialofetuin sialyltransferase activity was found to be 2 times higher in the atherosclerotic intima as compared to the normal intima and 2-fold higher in patients' plasma than in that from healthy donors. The mean values of the apparent Michaelis constant (K(m)) for the sialylating enzyme for both tissues did not differ and were close for the intima and plasma. In contrast, the maximal velocity (V(max)) was 2 times higher for the atherosclerotic intima than for the normal intima and 3 times higher for patients' plasma than for that of the donors. These results suggest that the activity of asialofetuin sialyltransferases of aortal intima is enhanced in atherosclerosis as is the secretion of their soluble forms into patients' plasma. PMID- 11781158 TI - Where the boys aren't: dioxin and the sex ratio. AB - The question of how exposure to dioxins might affect only males and why it affects preferentially male embryos in the Seveso data presented by Mocarelli et al. remains intriguing. This enigma can be explained by the ovopathy concept, which addresses the determination of both the sex and the condition of the progeny. Antiandrogenic properties of dioxin alter the sperm-transit time and mating behavior, which provoke delay of fertilization of the oocyte (postovulatory overripeness of the oocyte). Antiestrogenic properties of dioxin during mid-cycle compromise both mucus liquefaction and maturation of the oocyte (preovulatory overripeness ovopathy). A positive dose-response of male-biased pathologic conceptuses is often followed by a negative one due to "vanishing male conceptuses." This dose-response fallacy is present in animal experiments and explains many otherwise unexplained phenomena related to dioxin contamination and other high-risk conceptions. PMID- 11781159 TI - Starlink corn: a risk analysis. AB - Modern biotechnology has dramatically increased our ability to alter the agronomic traits of plants. Among the novel traits that biotechnology has made available, an important group includes Bacillus thuringiensis-derived insect resistance. This technology has been applied to potatoes, cotton, and corn. Benefits of Bt crops, and biotechnology generally, can be realized only if risks are assessed and managed properly. The case of Starlink corn, a plant modified with a gene that encodes the Bt protein Cry9c, was a severe test of U.S. regulatory agencies. The U.S. Environmental Protection Agency had restricted its use to animal feed due to concern about the potential for allergenicity. However, Starlink corn was later found throughout the human food supply, resulting in food recalls by the Food and Drug Administration and significant disruption of the food supply. Here we examine the regulatory history of Starlink, the assessment framework employed by the U.S. government, assumptions and information gaps, and the key elements of government efforts to manage the product. We explore the impacts on regulations, science, and society and conclude that only significant advances in our understanding of food allergies and improvements in monitoring and enforcement will avoid similar events in the future. Specifically, we need to develop a stronger fundamental basis for predicting allergic sensitization and reactions if novel proteins are to be introduced in this fashion. Mechanisms are needed to assure that worker and community aeroallergen risks are considered. Requirements are needed for the development of valid assays so that enforcement and post market surveillance activities can be conducted. PMID- 11781160 TI - Dioxins and endometriosis: a plausible hypothesis. AB - A potential connection exists between exposure to organochlorine chemicals and the increasing prevalence of endometriosis. Evidence shows that dioxin (2,3,7,8 tetrachlorodibenzo-p-dioxin) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of endometrial tissue implanted into rodents in a surgically induced model of endometriosis. The mechanism of the connection between organochlorine chemicals and endometriosis is not clear. Effects on growth factors, cytokines, and hormones (components of the immune and endocrine systems) are potential means of mediating the possible promotion of endometriosis by dioxins. Studies on epidemiology and on structure activity relationships of organochlorine chemicals and endometriosis have been additional approaches to this problem. In this regard, toxic equivalence (TEQ) appears to be an important determinant of the effects of organochlorine chemicals on endometriosis. In this article, we review the literature related to endometriosis and dioxins and attempt to integrate the various sources of information that bolster the hypothesis connecting dioxins and endometriosis. PMID- 11781161 TI - Exposure assessment to dioxins from the use of tampons and diapers. AB - Over the past several years there has been concern over exposure to dioxins through the use of tampons and other sanitary products. This article describes attempts to estimate dioxin exposures from tampons and infant diapers; we then compare exposure estimates to dietary dioxin exposures. We analyzed four brands of tampons and four brands of infant diapers obtained from commercial establishments in San Francisco, California, for dioxin concentrations. We estimated exposures to dioxins on the basis of a screening level analysis that assumed all dioxins present were completely absorbed. We also estimated exposures by using a more refined analysis that incorporates partition coefficients to estimate bioavailability. None of the products contained 2,3,7,8 tetrachlorodibenzo-p-dioxin, the most potent dioxin, although other dioxins were present at detectable concentrations in all samples. We observed minimal differences in the concentrations of dioxins between 100% cotton and cotton/pulp products. The refined exposure analysis indicates that exposures to dioxins from tampons are approximately 13,000-240,000 times less than dietary exposures. The refined exposure analysis showed that exposure to dioxins from the diet is more than 30,000-2,200,000 times the exposure through diapers in nursing infants. Although dioxins are found in trace amounts in both cotton and pulp sanitary products, exposure to dioxins through tampons and diapers does not significantly contribute to dioxin exposures in the United States. PMID- 11781162 TI - Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. AB - A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chemicals for EDC activities is now statutorily mandated. Computational chemistry tools are important to biologists because they identify chemicals most important for in vitro and in vivo studies. Here we used a computational approach with integration of two rejection filters, a tree-based model, and three structural alerts to predict and prioritize estrogen receptor (ER) ligands. The models were developed using data for 232 structurally diverse chemicals (training set) with a 10(6) range of relative binding affinities (RBAs); we then validated the models by predicting ER RBAs for 463 chemicals that had ER activity data (testing set). The integrated model gave a lower false negative rate than any single component for both training and testing sets. When the integrated model was applied to approximately 58,000 potential EDCs, 80% (approximately 46,000 chemicals) were predicted to have negligible potential (log RBA < -4.5, with log RBA = 2.0 for estradiol) to bind ER. The ability to process large numbers of chemicals to predict inactivity for ER binding and to categorically prioritize the remainder provides one biologic measure to prioritize chemicals for entry into more expensive assays (most chemicals have no biologic data of any kind). The general approach for predicting ER binding reported here may be applied to other receptors and/or reversible binding mechanisms involved in endocrine disruption. PMID- 11781163 TI - Attenuation of both apoptotic and necrotic actions of cadmium by Bcl-2. AB - We examined the effects of cadmium on the bcl-2 family of proteins--bcl-2, bax, bad, and bcl-xS/L--in cadmium-induced cytotoxicity. Addition of 10 microM cadmium to cultured porcine kidney LLC-PK(1) cells caused apoptosis. Western blot analyses revealed that cadmium markedly increased endogenous bcl-2 protein (to 3 4 times the level in wild-type cells) earlier than metallothionein induction, but that the metal did not enhance the induction of bax, bad, or bcl-xS proteins. Cadmium also induced the transcript of bcl-2, with the amount of bcl-2 reaching a maximum at 1-2 hr of exposure; this increase occurred earlier than cadmium induced increase in the protooncogene such as c-myc. A cadmium-induced increase in endogenous bcl-2 protein was also seen in rat primary thymocytes. Overexpression of the bcl-2 protein by gene transfection prevented cadmium induced apoptosis. Following the detection of apoptosis, lactate dehydrogenase release in the culture medium (a marker of necrosis) was observed, and this release was also inhibited by overexpression of bcl-2. Electron microscopic observations also supported the fact that cadmium induced apoptotic chromatin condensation at an early stage of exposure, followed by necrotic features of the cells, both of which were also inhibited by overexpression of bcl-2 proteins. Thus, our data demonstrated that both apoptotic and necrotic actions of cadmium were attenuated by bcl-2. PMID- 11781164 TI - Air conditioning and source-specific particles as modifiers of the effect of PM(10) on hospital admissions for heart and lung disease. AB - Studies on acute effects of particulate matter (PM) air pollution show significant variability in exposure-effect relations among cities. Recent studies have shown an influence of ventilation on personal/indoor-outdoor relations and stronger associations of adverse effects with combustion-related particles. We evaluated whether differences in prevalence of air conditioning (AC) and/or the contribution of different sources to total PM(10) emissions could partly explain the observed variability in exposure-effect relations. We used regression coefficients of the relation between PM(10) and hospital admissions for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and pneumonia from a recent study in 14 U.S. cities. We obtained data on the prevalence of AC from the 1993 American Housing Survey and data on PM(10) emissions by source category, vehicle miles traveled (VMT), and population density from the U.S. EPA. We analyzed data using meta-regression techniques. PM(10) regression coefficients for CVD and COPD decreased significantly with increasing percentage of homes with central AC when cities were stratified by whether their PM(10) concentrations peaked in winter or non-winter months. PM(10) coefficients for CVD increased significantly with increasing percentage of PM(10) emission from highway vehicles, highway diesels, oil combustion, metal processing, decreasing percentage of PM(10) emission from fugitive dust, and increasing population density and VMT/mile(2). In multivariate analysis, only percentage of PM(subscript)10(/subscript) from highway vehicles/diesels and oil combustion remained significant. For COPD and pneumonia, associations were less significant but the patterns of the associations were similar to that for CVD. The results suggest that air conditioning and proportion of especially traffic-related particles significantly modify the effect of PM(10) on hospital admissions, especially for CVD. PMID- 11781165 TI - Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats. AB - In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta), as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide ((232)Th), Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5 x 2.5 x 1.5 mm or 5.0 x 5.0 x 1.5 mm) or four pellets (2.0 x 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 x 5.0 x 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 x 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 x 2.5 mm DU squares and with 5.0 x 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 x 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats. PMID- 11781166 TI - Air pollution and daily mortality: a hypothesis concerning the role of impaired homeostasis. AB - We propose a hypothesis to explain the association between daily fluctuations in ambient air pollution, especially airborne particles, and death rates that can be tested in an experimental model. The association between airborne particulates and mortality has been observed internationally across cities with differing sources of pollution, climates, and demographies and has involved chiefly individuals with advanced chronic illnesses and the elderly. As these individuals lose the capacity to maintain stable, optimal internal environments (i.e., as their homeostatic capacity declines), they become increasingly vulnerable to external stress. To model homeostatic capacity for predicting this vulnerability, a variety of regulated physiologic variables may be monitored prospectively. They include the maintenance of deep body temperature and heart rate, as well as the circadian oscillations around these set-points. Examples are provided of the disruptive changes shown by these variables in inbred mice as the animals approach death. We consider briefly the implications that the hypothesis may hold for several epidemiologic issues, including the degree of prematurity of the deaths, the unlikelihood of a threshold effect, and the role that coarse, noncombustive particles may play in the association. PMID- 11781167 TI - A tale of two cities: effects of air pollution on hospital admissions in Hong Kong and London compared. AB - The causal interpretation of reported associations between daily air pollution and daily admissions requires consideration of residual confounding, correlation between pollutants, and effect modification. If results obtained in Hong Kong and London--which differ in climate, lifestyle, and many other respects--were similar, a causal association would be supported. We used identical statistical methods for the analysis in each city. Associations between daily admissions and pollutant levels were estimated using Poisson regression. Nonparametric smoothing methods were used to model seasonality and the nonlinear dependence of admissions on temperature, humidity, and influenza admissions. For respiratory admissions (> or = 65 years of age), significant positive associations were observed with particulate matter < 10 microm in aerodynamic diameter (PM(10), nitrogen dioxide, sulfur dioxide, and ozone in both cities. These associations tended to be stronger at shorter lags in Hong Kong and at longer lags in London. Associations were stronger in the cool season in Hong Kong and in the warm season in London, periods during which levels of humidity are at their lowest in each city. For cardiac admissions (all ages) in both cities, significant positive associations were observed for PM(10), NO(2), and SO(2) with similar lag patterns. Associations tended to be stronger in the cool season. The associations with NO(2) and SO(2) were the most robust in two-pollutant models. Patterns of association for pollutants with ischemic heart disease were similar in the two cities. The associations between O(3) and cardiac admissions were negative in London but positive in Hong Kong. We conclude that air pollution has remarkably similar associations with daily cardiorespiratory admissions in both cities, in spite of considerable differences between cities in social, lifestyle, and environmental factors. The results strengthen the argument that air pollution causes detrimental short-term health effects. PMID- 11781168 TI - The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production. AB - Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo. PMID- 11781169 TI - A consistent approach for the application of pharmacokinetic modeling in cancer and noncancer risk assessment. AB - Physiologically based pharmacokinetic modeling provides important capabilities for improving the reliability of the extrapolations across dose, species, and exposure route that are generally required in chemical risk assessment regardless of the toxic end point being considered. Recently, there has been an increasing focus on harmonization of the cancer and noncancer risk assessment approaches used by regulatory agencies. Although the specific details of applying pharmacokinetic modeling within these two paradigms may differ, it is possible to identify important elements common to both. These elements expand on a four-part framework for describing the development of toxicity: a) exposure, b) tissue dosimetry/pharmacokinetics, c) toxicity process/pharmacodynamics, and d) response. The middle two components constitute the mode of action. In particular, the approach described in this paper provides a common template for incorporating pharmacokinetic modeling to estimate tissue dosimetry into chemical risk assessment, whether for cancer or noncancer end points. Chemical risk assessments typically depend upon comparisons across species that often simplify to ratios reflecting the differences. In this paper we describe the uses of this ratio concept and discuss the advantages of a pharmacokinetic-based approach as compared to the use of default dosimetry. PMID- 11781170 TI - The characterization of upper-room ultraviolet germicidal irradiation in inactivating airborne microorganisms. AB - In this study, we explored the efficacy of upper-room ultraviolet germicidal irradiation (UVGI) in reducing the concentration of Serratia marcescens and Mycobacterium bovis bacille Calmette-Guerin (BCG) aerosols in enclosed places. We constructed a facility (4.5 m x 3 m x 2.9 m) in which both ceiling- and wall mounted UV fixtures (UV output: 10W and 5W respectively) were installed. The use of ceiling- and wall-mounted UV fixtures (total UV output: 15W) without mixing fan reduced the concentration of S. marcescens aerosols by 46% (range: 22-80%) at 2 air changes per hour (ACH) and 53% (range: 40-68%) at 6 ACH. The use of ceiling and wall-mounted UV fixtures with mixing fan increased the UV effectiveness in inactivating S. marcescens aerosols to 62% (range: 50-78%) at 2 ACH and to 86% (81-89%) at 6 ACH. For BCG aerosols, UV effectiveness in inactivating BCG aerosols at 6 ACH were 52% (range: 11-69%) by ceiling-mounted UV fixture only (total UV output: 10W) and 64% (51-83%) by both ceiling- and wall-mounted UV fixtures (total UV output: 15W). Our results indicated that the equivalent ventilation rate attributable to upper-room UVGI for BCG aerosols ranged from 1 ACH to 22 ACH for ceiling-mounted UV fixtures and from 6.4 ACH to 28.5 ACH for ceiling- and wall-mounted UV fixtures. Both generalized linear and generalized additive models were fitted to all our data. The regression results indicated that the number of UV fixtures, use of mixing fan, and air exchange rate significantly affected UV effectiveness (p < 0.01, 0.01, 0.01 respectively). However, the strain difference (S. marcescens vs. BCG) appeared less important in UV effectiveness (p = 0.26). Our results also indicated that UV effectiveness increased at higher temperature ((italic)p(/italic) < 0.01), lower dry-bulb temperature ((italic)p(/italic) = 0.21), and colder air from a supply grill located near the ceiling (p = 0.22). PMID- 11781171 TI - The effect of interior lead hazard controls on children's blood lead concentrations: a systematic evaluation. AB - Dust control is often recommended to prevent children's exposure to residential lead hazards, but the effect of these controls on children's blood lead concentrations is uncertain. We conducted a systematic review of randomized, controlled trials of low-cost, lead hazard control interventions to determine the effect of lead hazard control on children's blood lead concentration. Four trials met the inclusion criteria. We examined mean blood lead concentration and elevated blood lead concentrations (> or = 10 microg/dL, > or = 15 microg/dL, and > or = 20 microg/dL) and found no significant differences in mean change in blood lead concentration for children by random group assignment (children assigned to the intervention group compared with those assigned to the control group). We found no significant difference between the intervention and control groups in the percentage of children with blood lead > or = 10 microg/dL, 29% versus 32% [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.56-1.3], but there was a significant difference in the percentage of children with blood lead > or = 15 microg/dL between the intervention and control groups, 6% versus 14% (OR, 0.40; 95% CI, 0.21-0.80) and in the percentage of children with blood lead > or = 20 microg/dL between the intervention and control groups, 2% versus 6% (OR, 0.29; 95% CI, 0.10-0.85). We conclude that although low-cost, interior lead hazard control was associated with 50% or greater reduction in the proportion of children who had blood lead concentrations exceeding 15 microg/dL and > or = 20 microg/dL, there was no substantial effect on mean blood lead concentration. PMID- 11781173 TI - Blood lead concentration after a shotgun accident. AB - In an accidental shooting, a man in his late forties was hit in his left shoulder region by about 60 lead pellets from a shotgun. He had injuries to the vessels, the clavicle, muscles, and nerves, with total paralysis of the left arm due to axonal injury. After several surgical revisions and temporary cover with split skin, reconstructive surgery was carried out 54 days after the accident. The brachial plexus was swollen, but the continuity of the nerve trunks was not broken (no neuroma present). We determined the blood lead (BPb) concentration during a follow-up period of 12 months. The BPb concentration increased considerably during the first months. Although 30 lead pellets were removed during the reconstructive surgery, the BPb concentration continued to rise, and reached a peak of 62 microg/dL (3.0 micromol/L) on day 81. Thereafter it started to decline. Twelve months after the accident, BPb had leveled off at about 30 microg/dL. At that time, muscle and sensory functions had partially recovered. The BPb concentration exceeded 30 microg/dL for 9 months, which may have influenced the recovery rate of nerve function. Subjects with a large number of lead pellets or fragments embedded in the body after shooting accidents should be followed for many years by regular determinations of BPb. To obtain a more stable basis for risk assessment, the BPb concentrations should be corrected for variations in the subject's hemoglobin concentration or erythrocyte volume fraction. PMID- 11781172 TI - Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala. AB - In this study, we aimed to establish whether domestic use of wood fuel is associated with reduced birth weight, independent of key maternal, social, and economic confounding factors. We studied 1,717 women and newborn children in rural and urban communities in rural Guatemala. We identified subjects through home births reported by traditional birth attendants in six rural districts (n = 572) and all public hospital births in Quetzaltenango city during the study period (n = 1,145). All were seen within 72 hr of delivery, and data were collected on the type of household fuel used, fire type, and socioeconomic and other confounding factors. Smoking among women in the study community was negligible. Children born to mothers habitually cooking on open fires (n = 861) had the lowest mean birth weight of 2,819 g [95% confidence interval (CI), 2,790 2,848]; those using a chimney stove (n = 490) had an intermediate mean of 2,863 g (95% CI, 2,824-2,902); and those using the cleanest fuels (electricity or gas, n = 365) had the highest mean of 2,948 g (95% CI, 2,898-2,998) (p< 0.0001). The percentage of low birth weights (< 500 g) in these three groups was 19.9% (open fire), 16.8% (chimney stove), and 16.0% (electricity/gas), (trend (p = 0.08). Confounding factors were strongly associated with fuel type, but after adjustment wood users still had a birth weight 63 g lower (p = 0.05; 95% CI, 0.4-126). This is the first report of an association between biofuel use and reduced birth weight in a human population. Although there is potential for residual confounding despite adjustment, the better-documented evidence on passive smoking and a feasible mechanism through carbon monoxide exposure suggest this association may be real. Because two-thirds of households in developing countries still rely on biofuels and women of childbearing age perform most cooking tasks, the attributable risk arising from this association, if confirmed, could be substantial. PMID- 11781177 TI - New centers to focus on autism and other developmental disorders. PMID- 11781174 TI - The National Center for Toxicogenomics: using new technologies to inform mechanistic toxicology. PMID- 11781178 TI - Petroleum: possibilities in the pipeline. PMID- 11781179 TI - Renewable energy: empowering the developing world. PMID- 11781180 TI - Innovations: the gas is greener. PMID- 11781181 TI - Monocyte chemotactic protein-3. AB - Monocyte chemotactic protein-3 (MCP-3) belongs to the MCP subgroup of CC chemokines that are structurally closely related but, which differ in receptor usage and hence in biological activities. MCP-3 is one of the most pluripotent chemokines since it activates all types of leukocytes, by binding to at least four different chemokine receptors. The natural protein is heterogeneous due to glycosylation and NH2-terminal processing. Only small amounts of MCP-3 are induced in various cell types by endogeneous (cytokines) or exogeneous (bacteria, viruses) agents. Nevertheless, this omnipotent chemokine, inducible in most body compartments, might play an important role in normal homeostasis as well as in various pathologies including cancer, auto-immune diseases and chronic inflammation. PMID- 11781182 TI - Adenoviral supply of active transforming growth factor-beta1 (TGF-beta1) did not prevent lethality in transforming growth factor-beta1-knockout embryos. AB - In TGF-beta1-knockout mice, TGF-beta1-null conceptuses die during embryonic development with a penetrance of lethality that depends on the mouse genetic background. Studies have suggested that transplacental passage of maternal TGF beta1 could account for the rescue of some TGF-beta1-null embryos. Herein, we have used an adenovirus-based gene delivery system and a strain of mice where most TGF-beta1-null conceptuses die prior to parturition, to investigate whether an increase in maternal TGF-beta1 during pregnancy would rescue TGF-beta1-null embryos. A single intravenous injection of an adenovirus containing a modified version of TGF-beta1 cDNA (Ad-TGF-beta1S223/S225), coding for a biologically active form of the cytokine, induced a 20-fold increase in plasma TGF-beta1 (active and latent forms) levels for up to 3 months in adult mice. Similar levels of TGF-beta1 were detected in 13-day post coitum (dpc) embryos from Ad-TGF-beta1 treated mothers, demonstrating an efficient maternal/fetal transfer of the cytokine. However, no increase in the frequencies of TGF-beta1-null neonates nor in day 11.5 dpc TGF-beta1-null conceptuses was observed despite elevated levels of TGF-beta1 delivered throughout gestation. In addition, we show that the high levels of TGF-beta1-titrated in the plasma from Ad-TGF-beta1S223/S225-treated mice were partly the consequence of a stimulation of an autocrine production by exogenous bioactive TGF-beta1. These results indicate that transplacental passage of TGF-beta1 was not effective in rescuing TGF-beta1-null conceptuses from embryonic lethality. PMID- 11781183 TI - Absence of endogeneous interleukin-10 enhances the evolution of murine type-II collagen-induced arthritis. AB - Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 in the modulation of the inflammatory response in mice subjected to collagen-induced arthritis. Collagen-induced arthritis (CIA) was induced in mice lacking the gene for IL-10 (IL-10 "knock-out", IL-10KO) and in wild-type control (IL-10WT) mice by an intradermal injection of 100 mul of the emulsion (containing 100 mug of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. IL-10 wild type (WT) mice developed an erosive, hind paw arthritis when immunised with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged IL-10WT. The severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. IL-10KO mice experienced higher rates of clinical signs and more severe knee and paw injury as compared to IL-10WT. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Plasma levels of the proinflammatory cytokines, tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in comparison to wild-type mice. These data demonstrate that endogenous IL-10 exerts an anti-inflammatory role during chronic inflammation and tissue damage associated with collagen-induced arthritis, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation. PMID- 11781184 TI - Reduced adrenal response and increased mortality after systemic Klebsiella pneumoniae infection in interleukin-6-deficient mice. AB - During bacterial infections, both the immune system and the hypothalamus pituitary-adrenal (HPA) axis are activated. The role of IL-6 in the activation of the HPA axis during bacterial sepsis is not fully understood. The aim of the present study was to investigate the role of endogenous IL-6 in a potentially lethal infection with Klebsiella pneumoniae and the concomitant activation of the HPA axis. We examined the mortality of IL-6-/- and IL-6+/+ mice after intravenous (i.v.) infection with K. pneumoniae as well as the bacterial outgrowth in several organs. Subsequently, the influence of endogenous IL-6 on the effect of i.v. administration of K. pneumoniae on the plasma levels of corticosterone and the pro-inflammatory cytokines TNF-alpha and IL-1alpha was investigated in these mice. The present study demonstrates that IL-6-/- mice are more susceptible than IL-6+/+ mice to a systemic Gram-negative infection with K. pneumoniae, leading to increased outgrowth of microorganisms in the organs of the mice. Moreover, this infection is associated with a reduced adrenal response in IL-6-/- mice. We conclude that IL-6-/- mice are more susceptible to Gram-negative bacterial infections, which is mainly due to an impaired recruitment of granulocytes to the site of infection in the absence of IL-6. Furthermore, the reduced adrenal response may be an explanation for the strong inflammatory response with higher TNF-alpha plasma levels in IL-6-/- mice. PMID- 11781185 TI - Gamma-interferon induces apoptosis of the B lymphoma WEHI-279 cell line through a CD95/CD95L-independent mechanism. AB - Gamma-interferon (IFN-gamma) a cytokine produced by CD4+ T helper type 1 cells, CD8+ T cells and natural killer (NK) cells, plays a central role in the development of humoral and cell-mediated immunity. IFN-gamma participates in the maturation and differentiation of B cells, but it has been previously reported that IFN-gamma may inhibit the early stages of B cell activation. We report that the inhibition of the B lymphoma cell WEHI-279-proliferation induced by IFN gamma, involves the induction of typical features of apoptosis (nuclear chromatin condensation and fragmentation, cell shrinkage, phosphatidyl-serine (PS) exposure and mitochondrial membrane potential (delta psim) loss). IFN-gamma-mediated B cell apoptosis was decreased by the addition of the T helper type 2 cytokine, IL 4. WEHI-279 cells express CD95 and undergo apoptosis after treatment with either an agonistic anti-CD95 Ab or with a soluble recombinant CD95L. However, incubation with CD95-Fc or TRAIL-R1-Fc fusion proteins, did not prevent IFN-gamma mediated apoptosis, suggesting that IFN-gamma-mediated apoptosis occurs independently of CD95/CD95L and TRAIL-R/TRAIL interactions. IFN-gamma-mediated apoptosis is associated with caspase-3 activation that can be prevented by the addition of the broad caspase inhibitor zVAD-fmk. These data indicate that IFN gamma may play a major role in the regulation of B cell apoptosis, and suggest the involvement of an alternative pathway which is independent of the death receptors. PMID- 11781186 TI - IFN-beta stimulates the production of beta-chemokines in human peripheral blood monocytes. Importance of macrophage differentiation. AB - We investigated the effect of IFN-beta on beta-chemokine expression in differentiating human peripheral blood monocytes. MCP-1, MIP-1alpha and MIP-1beta were constitutively expressed in 1 day-cultured monocytes, and their secretion increased with time in culture despite any change in mRNA accumulation. IFN-beta treatment of differentiating monocytes resulted in a marked and dose-dependent increase of beta-chemokine secretion, which was regulated differently with respect to the differentiation stage. In particular, IFN-beta upregulated MCP-1 secretion in monocytes at all stages of differentiation although its effect was significantly higher in 1-day cultured monocytes as compared to monocyte-derived macrophages (MDM). In contrast, MIP-1alpha and MIP-1beta secretion was up regulated by IFN-beta only in MDM. Although MCP-1, MIP-1alpha and MIP-1beta mRNA expression was up-regulated by IFN-beta in both 1 day-cultured monocytes and MDM, no correlation was found between mRNA level and protein secretion. These results suggest that the regulation of beta-chemokine secretion in monocytes/macrophages by IFN-beta occurred through different mechanisms, involving both a direct effect of this cytokine on chemokine gene expression and translational/post translational steps of regulation more likely linked to the differentiation process. This finding reveals a novel role for this cytokine in the recruitment of specific cell types during the immune response, which may be relevant in the control of viral infections in vivo. PMID- 11781187 TI - Relationship between cell kinetics and apoptotic effects in TNF-alpha and IFN gamma-treated human tumour cell lines. AB - TNF-alpha is a potent inducer of apoptosis and also affects the transit of cells through the phases of the cell cycle. It is thought that the proliferation signalling pathway is related to the apoptosis pathway, the details of this cross talk are not yet fully understood. In this report, the effects of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human tumour cell lines with respect to proliferation and apoptosis are examined. The TNF-alpha sensitive cell lines Me-180 and MCF-7, the resistant cell line TCC-Sup, and the intermediate line 5637 were used. After a one day treatment, the transit through all phases of the cell cycle slowed down and after 3 days stopped completely, as measured with the BrdU-assay and flow cytometry. During the same time however, the levels of c-Myc and Ki-67 expression and the number of cells becoming apoptotic increased. Combined treatment with TNF-alpha and IFN-gamma augmented both the effects on the cell cycle and on apoptosis in the sensitive lines, and had only a minor additional effect on the resistant cell line as compared to single TNF-alpha treatment. The cells becoming apoptotic detached from the culture flask bottom and floated in the medium. Several apoptosis assays were used to prove that the floating cells were indeed apoptotic. As a subsidiary result of receptor measurement, we observed complexes of TNF-alpha receptors I with TNF-alpha receptors II using the related blocking antibodies and I125-TNF alpha as ligand. The association of proliferative parameters and apoptosis became obvious by plotting the levels of c-Myc expression versus remaining live cells after apoptotic cells were detached. Our data revealed a good linear correlation indicating that high levels of c-Myc render cells sensitive to apoptosis, independent of the treatment, TNF-alpha alone or TNF-alpha in combination with IFN-gamma. The quantitative linear correlation may point to a threshold mechanism. PMID- 11781188 TI - L-Buthionine-(S,R)-sulfoximine, an irreversible inhibitor of gamma glutamylcysteine synthetase, augments LPS-mediated pro-inflammatory cytokine biosynthesis: evidence for the implication of an IkappaB-alpha/NF-kappaB insensitive pathway. AB - The pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, contribute to the exacerbation of pathophysiological conditions in the lung. The regulation of cytokines involves the reduction oxidation (redox)-sensitive nuclear factor-kappaB (NF-kappaB), the activation of which is mediated through an upstream kinase that regulates the phosphorylation and subsequent degradation of inhibitory-kappaB (IkappaB)-alpha, the major cytosolic inhibitor of NF-kappaB. It was hypothesized that lipopolysaccharide (LPS)-induced biosynthesis of TNF-alpha and IL-6 in vitro is tightly regulated by redox equilibrium. Furthermore, the likely involvement of the IkappaB-alpha/NF kappaB signalling transduction pathway in mediating redox-dependent regulation of LPS-induced cytokine biosynthesis was revealed. Using alveolar epithelial cells, the role of L-buthionine-(S,R)-sulfoximine (BSO), a specific and irreversible inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in glutathione (GSH - an antioxidant thiol) biosynthesis, in regulating LPS-mediated TNF-alpha and IL-6 production and the IkappaB-alpha/NF-kappaB signalling pathway was investigated. Pre-treatment with BSO, prior to exposure to LPS augmented, in a dose-dependent manner, LPS-induced TNF-alpha and IL-6 biosynthesis, an effect associated with the induction of intracellular accumulation of reactive oxygen species (ROS). Interestingly, BSO blocked the phosphorylation of IkappaB-alpha, reduced its degradation, thereby allowing its cytosolic accumulation, and subsequently inhibited the activation of NF-kappaB. These results indicate that there are ROS and redox-mediated effects regulating pro-inflammatory cytokines, and that the IkappaB-alpha/NF-kappaB pathway is redox sensitive and differentially involved in mediating redox-dependent regulation of cytokine signaling. PMID- 11781190 TI - Regulation of Staphylococcus aureus-mediated activation of interleukin-18 in peripheral blood mononuclear cells. AB - Bacteria and bacterial antigens strongly induce cytokine secretion by peripheral blood leukocytes and thereby initiate an inflammatory cascade with potentially deleterious consequences for the host. The present study focussed on receptors and signal transduction pathways involved in activation of interleukin (IL)-18 by heat-inactivated Gram-positive Staphylococcus aureus Cowan strain I (SAC). Similarly to IL-12/IL-12p40, IL-10 and IFN-gamma, SAC dose-dependently activated IL-18. Secretion of IL-18 was independent of functional activity of IL-10, IL-12 or IFN-gamma. Lipoteichoic acid (LTA), a structural component of SAC, was not sufficient for activation of IL-18, while it dose-dependently induced IL-10. In contrast to IL-12, blockade of CD14 only partially diminished secretion of IL-18 and did not affect secretion of IL-10, suggesting involvement of other receptors (e.g., Toll-like receptors) in SAC responses. Further down-stream however, secretion of IL-10, IL-12 and IL-18 was uniformly inhibited by blockade of G protein-mediated kinase activation by mastoparan. Secretion of IL-18 required phosphatidylinositol-3'-kinase, and secretion of IL-12 phosphotyrosine kinase activity. The data demonstrate that SAC potently activates secretion of IL-18 by peripheral blood mononuclear cells with differential involvement of cell-surface receptors and signal transduction pathways as compared to other natural killer- and T cell-promoting cytokines. PMID- 11781189 TI - Endotoxin regulates the maturation of sterol regulatory element binding protein-1 through the induction of cytokines. AB - Endotoxin (LPS), by raising the levels of cytokines, markedly influences lipid metabolism. To clarify the molecular mechanism of this effect, we examined the action of endotoxin in vitro and in vivo on the regulation of sterol regulatory element binding protein-1 (SREBP-1). In HepG2 cells stimulated with LPS, a dose dependent increase in the level of the mature form of SREBP-1 was observed. For in vivo studies, endotoxin was administered intraperitoneally to CD1 mice fed with a standard or a cholesterol-enriched diet to increase the basal levels of circulating and liver cholesterol. Endotoxin raised cholesterol levels and stimulated the maturation of hepatic SREBP-1 in both normal and cholesterol-fed mice, indicating that the lipogenic effect of LPS was independent of endogenous sterol levels. To assess whether the lipogenic effect of endotoxin was linked to cytokine production, we administered LPS to C57Bl/6J endotoxin-sensitive and to C3H/HeJ endotoxin-resistant mice, which do not produce tumor necrosis factor in response to LPS. Significant induction of cholesterol levels and SREBP-1 activation was observed only in C57Bl/6J mice, indicating that cytokine production is crucial for the regulation of SREBP-1, and that the transcriptional activation of cholesterol biosynthesis may be part of the acute-phase response. PMID- 11781191 TI - Interleukine-6 (IL-6) synthesis and gp130 expression by human pericardium. AB - Growing evidence shows that cytokines of the IL-6 family play an important regulatory role in heart physiology such as inducing cardiomyocyte hypertrophy. The purpose of this study was to see if IL-6 and its soluble receptors (sIL-6R and sgp130) could be detected in pericardial fluids, and to see if they are produced by the pericardium. We report that human pericardial fluid from patients with coronary pathologies contained IL-6, sIL-6R, and sgp130. However, the levels present in sera and pericardial fluid did not correlate, which suggests local production. This observation was confirmed by in vitro studies demonstrating massive IL-6 production by cultured pericardial samples, which could be strongly inhibited by methylprednisolone. RT-PCR studies revealed that IL-6 was weakly expressed in fresh tissues and strongly induced after culture. In situ hybridisation and immunohistochemical analysis showed that IL-6 and gp130 were mainly present in mesothelial cells. sIL-6R and sgp130 were also produced by pericardium in vitro, and their synthesis was upregulated by methylprednisolone. Taken together, these results demonstrate that IL-6 is present in pericardial fluid and that its presence could be due to synthesis by pericardial tissue. In vitro studies suggest that IL-6 production by this tissue could be strongly induced and regulated. A potential paracrine role of these factors in cardiomyocyte functions in normal or pathological conditions is discussed. PMID- 11781192 TI - Plasmodium falciparum liver-stage antigen-1 peptide-specific interferon-gamma responses are not suppressed during uncomplicated malaria in African children. AB - Liver-stage antigen (LSA)-1 is a candidate vaccine molecule for Plasmodium falciparum malaria, but knowledge of the evolution of naturally acquired immune responses to LSA-1 in African children is lacking. We therefore assessed cellular immune responses to two defined T cell epitopes of LSA-1, during and after uncomplicated P. falciparum malaria in a group of Gabonese children. In terms of their prevalence, interferon (IFN)-gamma responses of peripheral blood mononuclear cells (PBMC) to an LSA-1 N-terminal peptide, T1, were significantly higher when measured during the acute phase compared with convalescence. IFN gamma responses to the LSA-J (hinge region) peptide showed a similar profile, but at a lower prevalence. Depletion experiments confirmed that CD8+ T cells are a major source of peptide-driven IFN-gamma, but both lymphoproliferation and the production of IL-10 in response to either of the peptides was low in all children at all times. PBMC from 25% of the children failed to produce IFN-gamma in response to either peptide at any time-point. The results suggest that lymphocytes producing IFN-gamma in response to at least one T cell epitope of LSA 1 are most frequent in the peripheral circulation during the acute phase of P. falciparum malaria. Thus, in this case, the generalised suppression of cell mediated responses which characterises acute malaria does not affect liver-stage antigen-specific IFN-gamma production. These findings imply that measurements of the frequency of parasite antigen-specific cellular immune responses in clinically healthy individuals may represent significant underestimations, which has important implications for the design of field-based vaccine antigen-related studies. PMID- 11781193 TI - Immunoexpressions of p21, Rb, mcl-1 and bad gene products in normal, hyperplastic and carcinomatous human prostates. AB - A comparative study of the expression of p21, Rb, mcl-1, and bad gene products, which are involved in the control of the cell cycle, was performed in normal, hyperplastic, and carcinomatous human prostates by means of a semiquantitative immunochemical study. This included Western blot, ELISA, and immunohistochemistry procedures. In normal prostates, immunoexpression of the four gene products was scanty or absent. In men with benign prostatic hyperplasia, immunoreactions to the four proteins studied were found in many epithelial cells and some stromal cells. In prostatic carcinoma, the immunostaining pattern was as in hyperplastic prostates but the numbers of both epithelial and stromal cells were higher. Present results indicate that immunoexpression of p21, Rb (both the phosphorylated and dephosphorylated forms), mcl-1, and bad gene products are markedly increased in prostates with proliferative alterations but that these proteins do not discriminate between benignant (hyperplasia) and malignant (adenocarcinoma) prostatic tumours, although immunoexpression is higher in prostatic carcinoma. PMID- 11781194 TI - Recombinant human interleukin-1 beta: new possibilities for the prophylaxis and correction of toxic myelodepression in patients with malignant tumors. I. Phase I II clinical trials of recombinant human interleukin-1 beta as a leukopoiesis stimulator in cancer patients receiving combination chemotherapy. AB - Human recombinant interleukin-1 beta (IL-1beta), administered by intravenous drop infusion, at doses of 10-20 ng/kg daily over 5 days, to a group of 67 patients suffering from malignant tumors and with grade II-IV toxic leukopenia, caused an increase in the leukocyte count to the normal value, within, on average, 8 +/- 1 days. The leukostimulatory effect of IL-1beta, administered subcutaneously at an average dose of 4.6 +/- 0.3 ng/kg (n = 16), appeared to be almost equal to that found for intravenous drop infusion at a dose of 10-20 ng/kg (n = 67). In patients receiving subcutaneous IL-1beta injections, the peripheral blood total leukocyte and granulocyte counts achieved normal values within 9 days. The side effects of IL-1beta at a dose of 0.1-20.0 ng/kg were well tolerated. PMID- 11781196 TI - French society of immunology, cytokines. June 7-8, 2001, Le Croisic, Port-Aux Rocs, France. PMID- 11781195 TI - Recombinant human interleukin-1 beta: new possibilities for the prophylaxis and correction of toxic myelodepression in patients with malignant tumors. II. Phase II study of the protective effect of recombinant human interleukin-1 beta on myelodepression induced by chemotherapy in cancer patients. AB - The clinical study of human recombinant IL-1beta as a leukopoiesis protector, administered intravenously and subcutaneously, simultaneously with the chemotherapy, confirmed the "protective" effect of this cytokine in patients with grade II leukopenia induced by previous cycles of chemotherapy. The highly protective effect of IL-1beta was proved by the normalization of absolute peripheral blood granulocyte counts over 5 days, from the start of hemostimulation in patients with leukopenia induced by previous cycles of chemotherapy, despite the continuation of cytostatic treatment. Changing the method of IL-1beta administration from the intravenous to the subcutaneous route had no statistically significant effect on the protective influence of IL-1beta. The time taken for complete restoration of leukopoiesis was almost the same for both methods, 5 +/- 1 days and 7 +/- 1 days for s.c. and i.v. methods respectively. This effect of IL-1beta, not seen in other hematopoietic growth factors such as GM-CSF and G-CSF, allows greater flexibility as regards chemotherapy and provides increased effectiveness of anticancer treatments. PMID- 11781197 TI - Editorial A brief history of EEG analysis before the 2001 odyssey. PMID- 11781198 TI - Dipole modeling of interictal and ictal EEG and MEG paroxysms. AB - Dipole modeling procedures can be used to statistically estimate the location and the orientation of intracerebral sources of electroencephalographic (EEG) and magnetoencephalographic (MEG) signals. These methods have been applied to interictal spikes for more than 20 years and suggest that interictal paroxysms might be generated by a network of cortical structures rather than by a focal area. In this review we address the questions of (1) the spatial extend of this network in different types of epilepsies, (2) the spatial relationship between this network and other structural of functional abnormalities as assessed by Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET), and (3) the reliability of dipole sources of interictal and ictal paroxysms. Dipole modeling results suggest that, in temporal lobe epilepsies, both neocortical and mesio-temporal structures are involved during interictal spikes; frontal lobe epilepsies are often characterized by more complex source distributions, that, in general, involve a large area and bilateral frontal structures. In addition, dipole modeling results are also found in close agreement with MRI data in cases where focal dysplasia or heterotopia are diagnosed. Nevertheless, in most other cases, sources of interictal spikes and MRI lesions, though overlapping in space, are not totally congruent. The best concordance between sources of interictal spikes and glucose hypometabolism on PET data is usually found for temporal lobe epilepsies. Most often, intracranial and intracerebral recordings validate both the localization and the time activation of interictal spike dipoles. However, results obtained for ictal discharges are less reliable, which therefore addresses the usefulness of dipole modeling procedures in assessing sources of ictal discharges. In conclusion, dipole modeling results can rarely be used in planning a selective surgery without invasive recordings. However, the studies reviewed in this paper strongly suggest that their analysis, in combination with other non-invasive data, might be useful to better delineate the epileptogenic zone, and help the implantation of intracerebral electrodes. PMID- 11781199 TI - Influence of the critical EEG pattern on blood flow variations measured by single photon computed emission tomography. AB - Anatomo-electro-clinical correlation's using stereo-electro-encephalography (SEEG) or electro-cortico-graphy (EcoG) are the gold standard for delineating the epileptic zone (EZ) in patients with partial epilepsy. These two techniques reflect the temporal and spatial dimensions of the epileptic fit. More recently, ictal Single Photon Computed Tomography (SPECT) compared with interictal SPECT allows anatomo-clinical correlations. SPECT reflects variations of the regional cerebral blood flow (rCBF) during the seizure. These variations of the rCBF are linked with the electrical activity but the relations between electrical activity and rCBF have not been well studied and it is still difficult to compare ictal/interictal SPECT with the SEEG and EcoG data to delineate the EZ. From the few published studies, we know that, if the injection of the SPECT tracer is performed at the onset of the seizure, while the fast ictal discharge is still going on, we shall observe a local hyperperfusion in the region where the discharge started and in the region where it propagated secondarily. If the tracer injection is performed late during the seizure, or after the end of it, we shall observe a local hypoperfusion in these regions, this has also a good localizing value. Time of injection must be known, as it represents a key issue for SPECT interpretation. PMID- 11781200 TI - Localization of distributed sources and comparison with functional MRI. AB - Functional mapping of the human brain has made tremendous progress in the past years thanks to new technical developments. Imaging methods are now available; they allow to study brain functions with high spatial and temporal resolution. Single photon emission computer tomography (SPECT), positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and high resolution electro- and magnetoencephalography (EEG and MEG) are currently intensively applied techniques to functional studies, each one having specific properties concerning spatial and temporal resolution. The success of these methods in basic neuroscience research has led to the demand for applying them to clinical questions. Diseases of the central nervous system that lead to brain dysfunction can be ideally explored using these techniques. Of particular importance are those diseases in which a focal neuronal dysfunction is the primary cause and where surgical resection of this focus might be the cure. This is often the case for epilepsy, where a discrete primary focus might exist from which pathological rhythms evolve and propagate throughout the brain, leading to seizures that severely handicap the patient. Surgical resection of the primary focus is only possible if the focus can be exactly localized and adequately separated from functionally important areas. This is where these new functional imaging tools become important. The use of SPECT and PET for focus localization has been most extensively studied and their specificity and sensitivity are intensively discussed. In the last few years functional MRI has evolved as a new interesting tool in epileptic focus localization. The most important limitation of these techniques, however, is the temporal resolution. Since epileptic activity can propagate very fast, several hyper- or hypoactive regions are seen in the images and primary areas cannot be distinguished from regions of propagation. The only methods that have sufficient temporal resolution to follow neuronal activity in real time are the electrophysiological measures, i.e. the EEG and the MEG. Localization of the sources in the brain that produced a given surface electromagnetic field has become possible through algorithms that solve the so called "inverse problem". Several different algorithms exist and many groups begun to apply them to epileptic data with the aim to localize the focus of the pathological electrical discharges. This review article discusses the use of distributed EEG source localization procedures in the presurgical evaluation of patients with intractable focal epilepsy. In contrast to equivalent dipole models, distributed localization methods do not localize one active point in the brain but rather assume extended active areas, which is generally the case in epileptic activity. The methods shown here are based on linear numerical methods and are therefore less prone to errors when working with scattered solution spaces such as the one defined by anatomical constraints. Solutions constraint to the gray matter determined in the individual MRI are shown here. We illustrate three methods to increase the spatial resolution of the source localization procedures: One is to increase the number of recording channels to more than 100, the second to use linear methods of high precision to detect focal sources (EPIFOCUS), and the third to combine EEG source localization with EEG-triggered functional magnetic resonance imaging. The importance of EEG source localization for the interpretation of fMRI data will be particularly discussed in view of the important difference of the temporal resolution by the two methods. The localization methods can be applied to interictal as well as to ictal activity. In case of analysis of ictal EEG we propose to use full scalp frequency analysis to determine the time period of seizure onset and to localize the sources of the initial dominant frequency. PMID- 11781201 TI - Event-related variations in the activity of EEG-rhythms. Application to the physiology and the pathology of movements. AB - The averaging of the ongoing activity of the electroencephalogram (EEG) allows extracting the potentials that are time-locked and phase-locked to an event. These potentials are described as evoked potentials. There is another type of change in the ongoing EEG, which is time-locked but not phase-locked to an event: the EEG rhythm reactivity, also called "Event-Related Desynchronization and Synchronization" (ERD/ERS) by Pfurtscheller. These changes are often visible to the naked eye but they cannot be extracted by the averaging technique. Their quantification requires another method, which was suggested by Pfurtscheller and Aranibar in 1977. This method consists in measuring the temporal evolution of the power of EEG signal within a given frequency band before, during, and after an event. ERD corresponds to the decrease in power of an EEG rhythm related to an event. Conversely, ERS corresponds to an increase in amplitude of an EEG rhythm related to the event. ERD represents the activation of the subjacent cortical areas. ERS would partly traduce the setting at rest of the cortex; it would also be related to the somesthetics afferents inputs. This method can be applied to the study of cortical activation in many situations: memory tasks, auditory processing, attention, anticipatory behavior, and voluntary movement. Thus, a voluntary self-paced movement of the dominant hand is preceded by an ERD of mu and beta rhythms occurring respectively 2 000 and 1 500 ms before the movement onset. This ERD is recorded over the contralateral central region. It becomes bilateral at the movement onset and reaches its maximum at the movement offset. It is then followed by an ERS of the beta rhythms. We show that ERD/ERS phenomena vary with the type of movement, and that their study allows exploring the modifications of cortical excitability that are observed in Parkinson's disease and in epilepsy with focal motor seizures. PMID- 11781202 TI - Modeling EEG signals and interpreting measures of relationship during temporal lobe seizures: an approach to the study of epileptogenic networks. AB - This work is focused on the study of the epileptogenic zone organization (EZ) in humans, based on the analysis of stereoelectroencephalographic (SEEG) signals with signal processing methods, and more specially those dedicated to the estimation of signal interdependencies. In order to evaluate quantities provided by these methods and in order to relate them to the notion of functional coupling between cerebral structures, we developed a neurophysiologically relevant model able to generate EEG signals from organized networks of neural populations. We showed [2, 3] that the model can produce realistic multichannel epileptiform signals (when compared to real SEEG signals) under certain conditions (excitation/inhibition ratio within populations, uni/bi-directional coupling between populations). In this paper, the model framework is used to evaluate the performance of nonlinear regression analysis as a method to characterize couplings between cerebral structures from SEEG signals they produce. Two quantities, a nonlinear correlation coefficient and a direction index, respectively related to coupling parameters in the model (degree/direction) are presented. These two quantities are measured on real SEEG signals recorded in patients suffering from temporal lobe epilepsy and candidate for surgical treatment. Results show that the characterization of functional couplings leads to the identification of networks referred to as "epileptogenic networks" and that might be responsible for the triggering of seizures. These results also corroborate our previous results on the classification of temporal lobe epilepsies [4, 5] showing that a recurrent seizure pattern exists that can be classified on the basis of interactions between medial and lateral neocortical structures. From the identified networks, it is also possible to describe "propagation networks" with a different organization is different and which play a major role in the clinical expression of seizures. PMID- 11781203 TI - Seizure anticipation by non-linear EEG analysis. AB - The study of dynamical changes in the neural activity preceding an epileptic seizure allows the characterization of a pre-ictal state several minutes prior to seizure onset. This opens new perspectives for studying the mechanisms of epileptogenesis as well as for possible therapeutic interventions which represent a major breakthrough. In this review we present and discuss the results from our group in this domain using nonlinear analysis of brain signals, as well as the limitations of this method and the remaining questions. PMID- 11781204 TI - Synchrony, from cognition to seizure. AB - It could seem strange that a same neuro-physiological mechanism provides for both normal and critical cerebral activity. While describing the basics of "cognitive" synchronies we will contrast them with the "critical" one for their differentiation and their non-rhythmic properties. Lastly we will speculate on their significance in the recently described seizure anticipation paradigm and on the possibility that they could share common generators. PMID- 11781205 TI - Preoperative rhinoplasty: evaluation and analysis. AB - In reality, the process of surgery is initiated at the moment patient and surgeon first meet. Patients arrive as candidates for surgery for a wide variety of reasons; motivational factors must be searched out and thoroughly evaluated by the surgeon. No completely accurate checklist exists to compute the psychologic makeup of individuals who seek facial plastic surgery. Before surgery is contemplated, significant education of patients is essential. This article examines the evaluative and analytical process of preoperative preparation for elective surgery. PMID- 11781206 TI - Local anesthetics for facial plastic procedures. AB - The use of local anesthetic in facial plastic surgical procedures is well established as an effective and safe mode of anesthesia delivery. Local infiltration of anesthesia may be used alone for minor surgical procedures, or it may be used with general anesthesia or intravenous sedation and analgesia for more complex, lengthy procedures. When considered independently, the use of local anesthetic agents has undeniable limitations. Local anesthetics can cause toxicity and side effects. Injection of local anesthetics for subcutaneous infiltration frequently is painful until sensory anesthesia occurs. Local anesthetics have limited efficacy with respect to the intensity and duration of sensory blockade that can be achieved. In some situations, use of local anesthesia with the maintenance of an awake patient also may be undesirable for the surgeon and impractical for the patient. Despite these shortcomings, local anesthetics are fundamentally ideal for use in facial plastic surgery. PMID- 11781207 TI - Update on chemical peels. AB - Facial skin rejuvenation continues to be a popular nonsurgical outpatient procedure performed by many facial plastic surgeons. Chemical peeling techniques continue to provide consistent and reliable results. By using variations of the Baker-Gordon solution and by varying the concentrations of TCA, several skin conditions may be treated. Because no one skin resurfacing procedure can be used for all patients, the most successful outcome is achieved when the treatment is individualized. Overall, skin resurfacing procedures remain one of the most rewarding procedures for the patient and surgeon. PMID- 11781208 TI - Collagen and injectable fillers. AB - Soft tissue augmentation of facial rhytids, scars, and deformities is a frequently performed office procedure. This article reviews the available biologic (collagen, Dermalogen, Autologen, Isolagen, autologous fat, Fibrel, hyaluronic acid derivatives, particulate fascia lata, micronized Alloderm) and alloplastic (silicone, Bioplastique, and Artecoll) soft tissue injectable fillers. PMID- 11781209 TI - Augmentation, enhancement, and implantation procedures for the lips. AB - Individual features of the face combine to capture the idealized image of youth and sensuality. In Western cultures, well-contoured lips contribute to this standard and are considered desirable attributes. In contrast, thin or drawn lips project a picture of aging and a severe countenance. In recent years, an increasing number of interventions have been introduced that seek to enhance lip fullness and shape. This article reviews the options available for lip augmentation with a focus on injectable and implantable materials. PMID- 11781210 TI - Cyanoacrylate tissue adhesives for skin closure in the outpatient setting. AB - Cyanoacrylate and fibrin tissue adhesives can aid the facial plastic surgeon performing surgery in the outpatient setting. Octyl-2-cyanoacrylate is ideal for superficial skin closure and eliminates the need for suture removal. Subcutaneous sutures are needed in most cases to provide the best cosmetic outcomes. Fibrin tissue adhesives can be used to aid in attaining hemostasis or to seal or fixate tissues. Cyanoacrylate and fibrin-based adhesives can simplify office-based facial plastic surgery. PMID- 11781211 TI - Laser skin resurfacing. AB - Laser skin resurfacing has become an important component of rejuvenation surgery. The laser allows for precise control of ablation depth and permits the surgeon to vary these depths as needed. The two wavelengths in common use are pulsed carbon dioxide and erbium:yttrium aluminum garnet. The principles and techniques of using these lasers for resurfacing and the practice of combining these wavelengths in sequence are described. Preprocedure and postprocedure measures also are discussed. PMID- 11781212 TI - Microepidermabrasion: an adjunct to medical skin care. AB - Microepidermabrasion has become a common modality in aesthetic skin care in doctor's offices as well as in the hands of skin care specialists. The basics of particle beam resurfacing are discussed, with an emphasis on patient selection, technique, and after care. Concerns about current technology are reviewed, and insight into the evolution of new technologies is given. PMID- 11781213 TI - Techniques in the removal of skin lesions. AB - The skin is one of the most easily accessible organs of the human body. Various skin lesions may be removed safely and easily in the office. This article describes various available methods, with suggestions regarding which method to use under selected circumstances. PMID- 11781214 TI - Botulinum toxin use in facial plastic surgery. AB - Botulinum toxin injection into specific mimetic facial muscle beds may be used alone or in conjunction with surgical modalities to rejuvenate the aging face and neck. PMID- 11781215 TI - Torn earlobe repair. AB - A variety of techniques have been described in the literature to repair torn earlobes. Some of these methods incorporate the reconstruction of the earring hole during earlobe repair, but many authors still recommend repiercing the earlobe at a later time. The present article is a comprehensive review of the published techniques for earlobe repair. Illustrations are provided to facilitate the description of the different methods and helpful recommendations are listed for a surgical approach to torn earlobes. PMID- 11781216 TI - Treatment of the keloid: what is new? AB - Keloids are benign lesions that represent an exuberant collagen response to injury. These benign lesions are plagued with high recurrence rates. Multitudes of options are available for treatment of these lesions, which supports the theory that there is no superior treatment. A variety of treatment options are discussed. PMID- 11781220 TI - Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry. AB - Acquired chromosomal anomalies (most commonly translocations) in lymphoma and leukemia usually result in either activation of a quiescent gene (by means of immunoglobulin or T-cell-receptor promotors) and expression of an intact protein product, or creation of a fusion gene encoding a chimeric protein. This review summarizes current immunocytochemical studies of these 2 categories of oncogenic protein, with emphasis on the clinical relevance of their detection in diagnostic samples. Among the quiescent genes activated by rearrangement, expression of cyclin D1 (due to rearrangement of the CCND1 [BCL-1] gene) is a near-specific marker of t(11;14) in mantle cell lymphoma; BCL-2 expression distinguishes follicular lymphoma cells from their nonneoplastic counterparts in reactive germinal centers and appears to be an independent prognostic marker in diffuse large cell lymphoma; and TAL-1 (SCL) expression identifies T-cell acute lymphoblastic neoplasms in which this gene is activated. The protein products of other genes activated by chromosomal rearrangement have a role as markers of either lineage (eg, PAX-5 [B-cell-specific activator protein] for B cells, including B-lymphoblastic neoplasms), or maturation stage (eg, BCL-6 for germinal center and activated B cells and MUM-1/IRF4 for plasma cells). Currently, no hybrid protein encoded by fusion genes is reliably detectable by antibodies recognizing unique junctional epitopes (ie, epitopes absent from the wild-type constituent proteins). Nevertheless, staining for promyelocytic leukemia (PML) protein will detect acute PML with t(15;17) because the microspeckled nuclear labeling pattern for PML-RARalpha is highly distinctive. Similarly, antibodies to the anaplastic lymphoma kinase (ALK) tyrosine kinase are valuable (because wild type ALK is not found in normal lymphoid tissue) in detecting neoplasms (CD30 positive large T-cell lymphomas) with t(2;5) or its variants. Thus, immunocytochemical detection of the products of many rearranged genes in lymphoma and leukemia can be clinically informative and provide information on cellular and subcellular protein expression that cannot be inferred from studies based on messenger RNA. PMID- 11781219 TI - Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells. AB - Hematopoietic stem cells (HSCs) represent an important target for the treatment of various blood disorders. As the source of critical cells within the immune system, genetic modification of HSCs can also be used to modulate immune responses. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. Self-inactivating (SIN) lentiviral vectors have been demonstrated to be capable of transducing mitotically inactive cells, including HSCs, and accommodating a nonviral promoter to control the transgene expression in transduced cells. In this study, we constructed 2 SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1alpha or the human HLA-DRalpha gene, which is selectively expressed in antigen-presenting cells (APCs). We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. When the EF.GFP vector was used, constitutive high-level GFP expression was obtained in all the human HSC progeny detectable in NOD/SCID mice and in subsequent in vitro differentiation assays, indicating that engrafting human HSCs have been transduced. In contrast, the DR.GFP vector mediated transgene expression specifically in human HLA-DR+ cells and highly in differentiated dendritic cells (DCs), which are critical in regulating immunity. Furthermore, human DCs derived from transduced and engrafted human cells potently stimulated allogeneic T-cell proliferation. This study demonstrated successful targeting of transgene expression to APCs/DCs after stable gene transduction of pluripotent HSCs. PMID- 11781221 TI - Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell-derived factor-1 and B lymphocyte chemoattractant. AB - Interleukin-10 (IL-10) is constitutively produced by peritoneal B1a lymphocytes, and stromal cell-derived factor-1 (SDF-1) by mesothelial cells. Independent studies have shown that both IL-10 and SDF-1 are involved in the persistence of the peritoneal B-lymphocyte compartment. This study shows that IL-10 and SDF-1 act in synergy on peritoneal B lymphocytes. Indeed, autocrine production of IL-10 was absolutely required for all effects of SDF-1 on these cells, including increased proliferation, survival, and chemotaxis. Moreover, adding IL-10 to peritoneal B lymphocytes increased the effects of SDF-1. Neither IL-5, IL-6, nor IL-9 affected the response of peritoneal B lymphocytes to SDF-1. IL-10 was chemokinetic for peritoneal B lymphocytes, increasing their random mobility. It also potentiated the SDF-1-induced reorganization of the cytoskeleton without affecting CXCR4 gene expression by peritoneal B lymphocytes. Despite its chemokinetic properties, IL-10 abolished the migration of peritoneal B lymphocytes in response to B-lymphocyte chemoattractant (BLC), a chemokine targeting B lymphocytes to lymphoid organ follicles. The ability of B1a lymphocytes to produce IL-10 constitutively, combined with the opposite effects of this cytokine on the responses to SDF-1 and BLC, may account for the selective accumulation of B1 lymphocytes in body cavities. PMID- 11781222 TI - Factor V Leiden: a genetic risk factor for thrombotic microangiopathy in patients with normal von Willebrand factor-cleaving protease activity. AB - Thrombotic microangiopathy (TM) is associated with abnormalities of von Willebrand factor-cleaving protease (VWCP) and other hemostatic factors. This study hypothesized that TM patients might have genetically determined thrombotic risk factors that predispose them to aberrant microvascular thrombosis. DNA samples from 30 white and 12 African American adult TM patients were analyzed for genetic alleles associated with vascular thrombosis, and plasma samples were analyzed for levels of VWCP activity. DNA was analyzed by using allele-specific polymerase chain reaction for factor V 1691A (Leiden), factor II 20 210A, methylenetetrahydrofolate reductase 667T, type 1 plasminogen activator inhibitor 4G/5G, and platelet GPIa 807T. Patients were segregated by race (white or African American) and plasma level of VWCP activity (normal or deficient). The prevalence of factor V Leiden was significantly increased among the white TM patients that had normal VWCP activity: 4 (36%) of 11 patients compared with 6 (3%) of 186 white control subjects possessed the factor V Leiden allele (P <.001; odds ratio, 17.1; 95% confidence interval, 5.4-54.0). No factor V Leiden alleles were detected in 19 white TM patients with intermediate or deficient levels of VWCP activity or in any of 12 African American patients. The prevalence of other thrombosis-associated alleles did not differ between TM patients and control subjects. These findings suggest that factor V Leiden may be a pathogenic risk factor in TM patients that have normal VWCP activity. PMID- 11781223 TI - Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state. AB - The inv(16) cytogenetic subtype of acute myeloid leukemia (AML) has a relatively good prognosis. Many patients achieve complete remission (CR). The prognostic uncertainty of negative qualitative reverse transcription-polymerase chain reaction (RT-PCR) assays suggests the need to identify prognostically significant critical thresholds by real-time RT-PCR. A reliable and sensitive (10(-5)) real time RT-PCR assay was set up for the evaluation of relevant CBFbeta-MYH11/ABL transcript ratios and was applied to the 21 patients with inv(16) AML routinely referred for cytogenetic and molecular monitoring in Seragnoli Institute (Bologna, Italy) since 1990. Among the 18 patients who underwent ablative chemotherapy, all achieved CR with a 3-year disease-free survival probability of 63% (95% CI, 40%-87%) and no recorded events after 26 months. Five patients had relapses; 2 died of disease and 3 entered second CR. Analysis of the 125 bone marrow (or peripheral blood) samples studied by real-time RT-PCR showed that transcript ratios of samples taken during CR at any time before a relapse were always greater than 0.12%, whereas those of samples taken during first or second CR from patients who did not subsequently have relapses were always less than 0.25%. This suggests that transcript ratios greater than 0.25% may correspond to high risk for relapse, whereas ratios below 0.12% might indicate the patient is in a curable state. If confirmed, such thresholds could open the way to a new phase in post-CR therapeutic decision making for patients with inv(16) AML. PMID- 11781224 TI - Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study. AB - Among patients with von Willebrand disease (VWD) who are unresponsive to desmopressin therapy, replacement with plasma-derived concentrates is the treatment of choice. Because prospective studies are lacking, such treatment has been largely empirical. A multicenter, prospective study has been conducted in 81 patients with VWD (15 patients with type 1, 34 with type 2, and 32 with type 3 disease) to investigate the efficacy of a high-purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate for treatment of bleeding and surgical prophylaxis. Two preparations of the concentrate-one virally inactivated with solvent detergent, the other with an additional heat-treatment step--were evaluated. Pharmacokinetic parameters were similar for both preparations. Using pre-established dosages based on the results of pharmacokinetic studies, 53 patients were administered either preparation for the treatment of 87 bleeding episodes, and 39 patients were treated prophylactically for 71 surgical or invasive procedures. Sixty-five (74.7%) and 10 (11.5%) of the bleeding episodes were controlled with 1 or 2 infusions, respectively. Patients with severe type 3 VWD typically required more infusions and higher doses, at shorter time intervals, than did patients with generally milder types 1 and 2. Among patients undergoing surgical procedures, blood loss was lower than that predicted prospectively, and losses exceeding the predicted value did not correlate with the postinfusion skin bleeding time. In conclusion, the concentrate effectively stopped active bleeding and provided adequate hemostasis for surgical or invasive procedures, even in the absence of bleeding time correction. PMID- 11781225 TI - Use of blood outgrowth endothelial cells for gene therapy for hemophilia A. AB - A culture of human blood outgrowth endothelial cells (BOECs) was established from a sample of peripheral blood and was transfected using a nonviral plasmid carrying complementary DNA for modified human coagulation factor VIII (B domain deleted and replaced with green fluorescence protein). BOECs were then chemically selected, expanded, cryopreserved, and re-expanded in culture. Stably transfected BOECs were administered intravenously daily for 3 days to NOD/SCID mice at 4 cell dose levels (from 5 x 10(4) to 40 x 10(4) cells per injection). In 156 days of observation, mice showed levels of human FVIII that increased with cell dose and time. Mice in all cell dose groups achieved therapeutic levels (more than 10 ng/mL) of human FVIII, and mice in the 3 highest dose groups acquired levels that were normal (100-200 ng/mL) or even above the normal range (highest observed value, 1174 ng/mL). These levels indicate that the BOECs expanded in vivo after administration. When the mice were killed, it was found that BOEC accumulated only in bone marrow and spleen and that these cells retained endothelial phenotype and transgene expression. Cell doses used here would make scale-up to humans feasible. Thus, the use of engineered autologous BOECs, which here resulted in sustained and therapeutic levels of FVIII, may comprise an effective therapeutic strategy for use in gene therapy for hemophilia A. PMID- 11781226 TI - Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver. AB - This article describes the isolation of a novel cell population (B220(lo)c kit(+)CD19(-)) in the fetal liver that represents 70% of T-cell precursors in this organ. Interestingly, these precursors showed a bipotent T-cell and natural killer cell (NK)- restricted reconstitution potential but completely lacked B and erythromyeloid differentiation capacity both in vivo and in vitro. Moreover, not only mature T-cell receptor (TCR)alphabeta(+) peripheral T cells but also TCRgammadelta(+) and TCRalphabeta(+)CD8alphaalpha(+) intestinal epithelial cells of extrathymic origin were generated in reconstituted mice. The presence of this population in the fetal liver of athymic embryos indicates its prethymic origin. The comparison of the phenotype and differentiation potential of B220(lo)c kit(+)CD19(-) fetal liver cells with those of thymic T/NK progenitors indicates that this is the most immature common T/NK cell progenitor so far identified. These fetal liver progenitors may represent the immediate developmental step before thymic immigration. PMID- 11781227 TI - Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5 deficient pre-B I-cell clones. AB - Pax5-deficient pre-B I-cell clones, transplanted into natural killer (NK)-cell deficient RAG2(-/-) IL-2Rgamma(-/-) hosts, populate the NK-cell compartment with functional NK cells. NK-cell generation from Pax5(-/-) pre-B I cells is also observed in NK-cell-proficient Balb/c RAG2(-/-) hosts. In the same Balb/c RAG2(-/ ) hosts, Pax5(-/-) pre-B I-cell clones not only populate the pre-B I-cell compartment and fill the deficient T-cell-lineage compartment in the thymus and the periphery of all hosts, as shown before, they also generate CD8alpha(-) and CD8alpha(+) dendritic cells (DCs), macrophages, and granulocytes in vivo in approximately half the hosts. In some recipients, practically all the mature myeloid cells are of Pax5(-/-) origin, indicating the effectiveness by which Pax5(-/-) pre-B I cells can compete with endogenous myeloid precursors. In a smaller percentage of hosts, the generation of Pax5(-/-) pre-B I-cell-derived erythrocytes is observed 4 to 6 months after transplantation. The results indicate that Pax5(-/-) pre-B I cells can develop in vivo in hosts that have undergone transplantation to erythroid, myeloid, and lymphoid cell lineages. Hence, the Pax5(-/-) mutation introduces an unusual instability of differentiation in pre-B I cells so that they appear to dedifferentiate as far back as the pluripotent hematopoietic stem cell. PMID- 11781228 TI - Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5. AB - Signal transducers and activators of transcription (STATs) are intracellular mediators of cytokine receptor signals. Because many early-acting growth factors have been implicated in STAT5 activation, this study sought to investigate whether STAT5 may be a transcriptional regulator of hematopoietic stem cell (HSC) long-term repopulating activity. To test this possibility, bone marrow (BM) and fetal liver (FL) cells from mice containing homozygous deletions of both STAT5a and STAT5b genes (STAT5ab(-/-)) were characterized for hematopoietic repopulating activities. BM and FL grafts were capable of repopulating lymphoid and myeloid lineages of lethally irradiated primary and secondary hosts, with defects observed primarily in T-lymphocyte engraftment. Because only a fraction of normal HSC function is required to reconstitute hematopoiesis, competitive repopulation assays of adult BM or FL cells were used against wild type adult BM or FL cells to quantitate stem cell function. In these analyses, average 25-, 28-, 45-, and 68-fold decreases in normal repopulating activity were evident in granulocyte (Gr 1(+)), macrophage (Mac-1(+)), erythroid progenitor (Ter119(+)), and B-lymphocyte (B220(+)) populations, respectively, with T lymphocytes (CD4(+)) always undetectable from the STAT5ab(-/-) graft. Consistent with previous reports of divergence between stem cell phenotype and function in cases of perturbed hematopoiesis, the absolute number of cells within Sca-1(+)c-kit(+)lin(-) or lin( ) Hoechst 33342 side population fractions was not significantly different between wild type and STAT5ab(-/-) BM or FL cells. These results demonstrate that a significant proportion of the growth factor signals required for multilineage reconstitution potential of HSCs is STAT5 dependent. PMID- 11781229 TI - Differential gene expression profiling of adult murine hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Five thousand cDNA clones with very low hybridization signals were selected for sequencing and further analysis using microarrays on glass slides. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. HSCs have the ability to self-renew, while MPP cells have lost the capacity for self renewal. A large number of genes that were differentially expressed by enriched populations of HSCs and MPP cells were identified. These included transcription factors, signaling molecules, and previously unknown genes. PMID- 11781231 TI - The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. AB - A promising and increasingly exploited property of hematopoietic stem cells is their ability to efflux the fluorescent dye Hoechst 33342. The Hoechst-negative cells are isolated by fluorescence-activated cell sorting as a so-called side "population" (SP) of bone marrow. This SP from bone marrow, as well as other tissues, is reported to contain immature stem cells with considerable plasticity. Some cell lines also efflux Hoechst and generate SP profiles. Reverse transcription-polymerase chain reaction (RT-PCR) and efflux inhibition studies with the lung carcinoma cell line, A549, implicated the ABCG2 transporter as a Hoechst efflux pump. Furthermore, it is shown that transient expression of ABCG2 generates a robust SP phenotype in human embryonic kidney (HEK293) cells. The results allow the conclusion that ABCG2 is a potent Hoechst efflux pump. Semiquantitative RT-PCR was used to characterize the developmental pattern of expression of ABCG2 in hematopoiesis. It is expressed at relatively high levels in putative hematopoietic stem cells (isolated as SP, 34+/38- or 34+/KDR+ populations) and drops sharply in committed progenitors (34+/38+, 34+/33+, or 34+/10+). Expression remains low in most maturing populations, but rises again in natural killer cells and erythroblasts. Comparison of messenger RNA (mRNA) levels for the 3 major multidrug-resistant efflux pumps, MDR1, MRP1, and ABCG2, in bone marrow SP cells reveals that ABCG2 is the predominant form in these cells. These data suggest that ABCG2 contributes significantly to the generation of the SP phenotype in hematopoietic stem cells. Furthermore, the sharp down-regulation of ABCG2 at the stage of lineage commitment suggests that this gene may play an important role in the unique physiology of the pluripotent stem cell. PMID- 11781230 TI - Molecular mechanism of transforming growth factor beta-mediated cell-cycle modulation in primary human CD34(+) progenitors. AB - The mechanisms by which transforming growth factor beta (TGF-beta) exerts a negative effect on cell-cycle entry in primary human hematopoietic stem/progenitor cells were examined at the molecular and cellular levels. After treatment of primary human CD34+ progenitors with TGF-beta there was a decrease in the levels of cyclin D2 protein and an increase in levels of the cyclin dependent kinase inhibitor (CDKI) p15 as compared to the levels in untreated cells. The converse was true after addition of neutralizing anti-TGF-beta antibody. Administration of TGF-beta to CD34+ cells in the presence of cytokines prevented retinoblastoma protein (pRb) phosphorylation, which occurred in the same cells treated with cytokines alone or cytokines and anti-TGF-beta antibody. Neutralization of TGF-beta during 24 to 48 hours of culture with cytokines significantly increased the number of colony-forming progenitors, but did not modulate the human stem cell pool, as measured in 6- to 12-month xenotransplantation assays. Equivalent numbers of human B, T, and myeloid cells were obtained after transplantation of cells treated with or without neutralization of TGF-beta. PMID- 11781232 TI - Enforced expression of the Ikaros isoform IK5 decreases the numbers of extrathymic intraepithelial lymphocytes and natural killer 1.1+ T cells. AB - The zinc-finger protein Ikaros plays an important role in lymphoid homeostasis, and loss of Ikaros expression through germline disruption impairs lymphoid development. However, the role played by Ikaros after commitment to the T-cell lineage is unclear. To address this question, this study used the lck proximal promoter to drive the expression in T-cell progenitors of a naturally occurring short Ikaros isoform (IK5), which lacks the DNA-binding domain, reasoning that IK5 will form heterodimers with long isoforms and perturb their function. The IK5 transgene led to a selective and dramatic decrease in extrathymic intestinal intraepithelial lymphocytes (IELs) and natural killer 1.1+ T (NK T) cells with little effect on conventional alphabeta T cells, which resembles the T-cell phenotype of interleukin-15 receptor alpha chain (IL-15Ralpha) and IL-2/IL-15 receptor beta chain (IL-2Rbeta) knockout mice. The expression of IL-2Rbeta on double-negative T-cell progenitors of bi-5 was reduced, but enforced expression of IL-2Rbeta did not rescue IELs or NK T cells in bi-5 transgenic mice, suggesting that Ikaros or Ikaros family members regulate the expression of additional genes that are essential for the development of IELs and NK T cells. The study concludes that modest changes in the ratio of short to long Ikaros isoforms can substantially perturb T-cell development, and the development of IELs and NK T cells is particularly sensitive to such changes. PMID- 11781233 TI - Cytokine-inducible CD40 expression in human endothelial cells is mediated by interferon regulatory factor-1. AB - Given the significance of CD40-CD40 ligand interactions in chronic inflammatory diseases including atherosclerosis, the transcriptional regulation of CD40 expression as a potential therapeutic target was investigated in human umbilical vein cultured endothelial cells. Exposure to interferon-gamma (IFN-gamma) plus tumor necrosis factor-alpha resulted in a marked synergistic de novo expression of CD40, which, according to electrophoretic mobility shift analysis, was attributable to activation of the transcription factors nuclear factor-kappaB (NF kappaB), signal transducer and activator of transcription-1 (STAT-1), and interferon regulatory factor-1 (IRF-1). Subsequent time-course studies revealed that de novo synthesis of IRF-1 preceded that of CD40. Decoy oligodeoxynucleotide (ODN) neutralization of STAT-1 or IRF-1, but not of NF-kappaB, inhibited cytokine stimulated CD40 expression by 60% at both the mRNA and protein levels, and this effect was mimicked by antisense ODN blockade of IRF-1 synthesis. In contrast, CD40 expression in response to IFN-gamma stimulation was sensitive to neutralization of STAT-1 only. These findings suggest that depending on the cytokine composition, CD40 expression in human endothelial cells under proinflammatory conditions is governed by STAT-1 either directly or indirectly through de novo synthesis of IRF-1. Moreover, decoy ODN neutralization of these transcription factors may provide a novel therapeutic option for interfering with CD40-CD40 ligand-mediated inflammatory responses in vivo. PMID- 11781234 TI - Plasma levels of endothelial protein C receptor respond to anticoagulant treatment. AB - The endothelial protein C receptor (EPCR) facilitates protein C activation and plays a protective role in the response to Escherichia coli-mediated sepsis in primates. Previously, a soluble form of EPCR (sEPCR) in human plasma was characterized, and several studies indicated that generation of sEPCR is regulated by inflammatory mediators, including thrombin-mediated up-regulation of surface metalloproteolytic activity in vitro. This study addressed the question of whether plasma sEPCR levels reflect changes in thrombin generation in patients undergoing anticoagulant treatment. The sEPCR levels in patients treated with coumarin-type oral anticoagulants were significantly lower than those in healthy asymptomatic adult volunteers (105.3 +/- 70.8 ng/mL [n = 55] versus 165.8 +/- 115.8 ng/mL [n = 200]; P <.0001). A similar decline in plasma sEPCR levels was found in patients treated with unfractionated heparin. In healthy volunteers, sEPCR levels declined to about 100 ng/mL within 3 days after initiation of an 8 day period of warfarin administration and increased within 2 days after its cessation. Plasma sEPCR levels returned to pretreatment values within 1 week, and the changes in plasma sEPCR levels mirrored changes in values for international normalized ratios. A similar decline in sEPCR levels with time was observed in 7 patients beginning treatment with warfarin for a thrombotic disorder. Prothrombin fragment 1 + 2 levels also decreased in volunteers and patients given warfarin. These results show that plasma sEPCR levels decline in response to treatment with anticoagulants whose mechanism of action is known to decrease in vivo thrombin production. PMID- 11781235 TI - Expression of the recombination-activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils. AB - V(D)J recombination in lymphocytes is mediated by 2 recombination-activating genes, RAG1 and RAG2, which are expressed during lymphocyte development in bone marrow and thymus. Prompted by studies reporting re-expression of the RAGs in germinal center B cells, the expression of RAGs and terminal deoxynucleotidyl transferase (TdT) in human lymphoid tissues was examined using in situ hybridization and immunohistochemistry, respectively. Here it is shown that RAGs and TdT are not reinduced in germinal center reactions. However, RAG(+)/TdT(+) cells are frequently present in extrafollicular areas of tonsils mainly at the boundary between lymphoid tissue and fibrous scaffold. Phenotypic analyses suggest that these cells are B cells. Finally, it is shown that RAG(+)/TdT(+) cells are found more frequently in tonsils than in other peripheral lymphoid tissues. This may reflect an increased influx of RAG(+)/TdT(+) cells as a result of higher antigenic stimulation at this site. Alternatively, this observation may indicate that the tonsils are an additional site of lymphocyte ontogeny. PMID- 11781236 TI - Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2--deficient mice. AB - Angiogenesis and enhanced microvascular permeability are hallmarks of a large number of inflammatory diseases. Although up-regulation of proangiogenic factors such as vascular endothelial growth factor and interleukin-8 have been previously reported in inflamed tissue, the biologic role of endogenous inhibitors of angiogenesis in inflammation has remained unclear. To investigate the biologic role of the potent angiogenesis inhibitor thrombospondin-2 (TSP-2) in the control of cutaneous inflammation, delayed-type hypersensitivity reactions were elicited in the ear skin of wild-type and TSP-2-deficient mice by topical sensitization and challenge with oxazolone. Cutaneous TSP-2 expression was up-regulated in the inflamed skin of wild-type mice, predominantly in dermal fibroblasts and microvessels. Lack of TSP-2 resulted in a significantly enhanced inflammatory response with increased angiogenesis, edema formation, and inflammatory infiltration. Ear swelling and inflammation persisted for more than 2 weeks in TSP-2-deficient mice, as compared with 1 week in wild-type mice. Although baseline vascular permeability was unchanged, significantly enhanced microvascular leakage was found in the inflamed skin of TSP-2-deficient mice. Moreover, the fraction of rolling leukocytes was significantly increased in the untreated skin of TSP-2-deficient mice. These results reveal an important role of TSP-2 in limiting the extent and the duration of edema formation, angiogenesis, and inflammatory cell infiltration during acute and chronic inflammation. PMID- 11781237 TI - Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development. AB - The present study investigated the potential role of stromal cell-derived factor 1 (SDF-1) in human intrathymic T-cell differentiation. Results show that SDF-1 is produced by human thymic epithelial cells from the subcapsular and medullary areas, and its receptor, CXCR4, is up-regulated on CD34(+) precursor cells committed to the T-cell lineage. Chimeric human-mouse fetal thymus organ culture (FTOC) seeded with purified CD34(+) thymic progenitors and treated with neutralizing antibodies against SDF-1 or CXCR4 showed a significant reduction of the number of human thymocytes and an arrested thymocyte differentiation in the transition between CD34(+) precursor cells and CD4(+) immature thymocytes. SDF-1 treated FTOC showed an increase of human thymocyte numbers, mainly affecting the most immature subpopulations. Moreover, these results suggest that CXCR4/SDF-1 signaling is not critical for the CD34(+) cell precursor recruitment to the thymus. On the other hand, SDF-1 significantly increased the viability of CD34(+) T-cell precursors modulating the expression of BCL-2 and BAX genes, and stimulated the proliferation of CD34(+) thymic precursor cells, particularly in synergy with interleukin 7 (IL-7), but not with other cytokines, such as stem cell factor or flt3-ligand. Accordingly, only IL-7 was able to up-regulate CXCR4 expression on CD34(+) thymic progenitors. In addition, deprivation of SDF-1 partially inhibited human thymocyte expansion induced by IL-7 in human-mouse FTOC. This study indicates that SDF-1/CXCR4 signaling is required for the survival, expansion, and subsequent differentiation of human early thymocytes and identifies a new mechanism by which IL-7 mediates its effects on human thymopoiesis. PMID- 11781238 TI - CD4(+)CD25(+) T-cell development is regulated by at least 2 distinct mechanisms. AB - It has recently been shown that CD4(+)CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T-cell-mediated organ-specific autoimmune diseases. In this study, the regulatory mechanism of CD4(+)CD25(+) T-cell development were investigated using T-cell receptor (TCR) transgenic mice. It was found that CD4(+)CD25(+) T cells preferentially expressed the endogenous TCRalpha chain in DO10(+) TCR transgenic mice compared with CD4(+)CD25(-) T cells. Moreover, it was found that CD4(+)CD25(+) thymocytes were severely decreased in DO10(+) TCR-alpha( /-) mice in positively selecting and negatively selecting backgrounds, whereas CD4(+)CD25(-) thymocytes efficiently developed by transgenic TCR in DO10(+) TCR alpha(-/-) mice in positively selecting backgrounds, indicating that the appropriate affinity of TCR to major histocompatibility complex (MHC) for the development of CD4(+)CD25(+) thymocytes is different from that of CD4(+)CD25(-) thymocytes and that a certain TCR-MHC affinity is required for the development of CD4(+)CD25(+) thymocytes. Finally, it was found that, in contrast to thymus, CD4(+)CD25(+) T cells were readily detected in spleen of DO10(+) TCR-alpha(-/-) mice in positively selecting backgrounds and that splenic CD4(+)CD25(+) T cells, but not CD4(+)CD25(+) thymocytes, were significantly decreased in B-cell deficient mice, suggesting that B cells may control the peripheral pool of CD4(+)CD25(+) T cells. Together, these results indicate that the development of CD4(+)CD25(+) T cells in thymus and the homeostasis of CD4(+)CD25(+) T cells in periphery are regulated by distinct mechanisms. PMID- 11781239 TI - Quantitative trait loci regulating relative lymphocyte proportions in mouse peripheral blood. AB - Relative proportions of peripheral blood (PB) B lymphocytes (B220%) as well as CD4 (CD4%) and CD8 (CD8%) T lymphocytes differ significantly among inbred mouse strains: B220% is high in C57BL/6J (B6) and C57BR/cdJ, intermediate in BALB/cByJ (BALB) and DBA/2J (D2), and low in NOD/LtJ (NOD) and SJL/J (SJL) mice, whereas CD4% and CD8% are high in NOD and SJL mice and low in the other 4 strains. By following segregating genetic markers linked to these traits in (B6 x D2) recombinant inbred (BXD RI) mice, the study defined 2 quantitative trait loci (QTLs) for the B220% phenotype: Pbbcp1 (peripheral blood B cell percentage 1, logarithm of odds [LOD] 4.1, P <.000 01) and Pbbcp2 (LOD 3.7, P <.000 04) on chromosome 1 (Chr 1) at about 63 cM and 48 cM; one suggestive locus for the CD4% phenotype (LOD 2.6, P <.000 57) on Chr 8 at about 73 cM; and one QTL for the CD8% phenotype: Pbctlp1 (peripheral blood cytotoxic T lymphocyte percentage 1, LOD 3.8, P <.000 02) on Chr 19 at about 12 cM. The study further segregated PB lymphocyte proportions in B6SJLF2 mice by using DNA markers adjacent to these mapped QTLs and found that the Pbbcp1 locus (LOD 5.6, P <.000 01) was also important in this mouse population. In both BXD RI and B6SJLF2 mice, QTLs regulating B-cell proportions showed no significant effect on T-cell proportions and vice versa. Thus, PB B- and T-lymphocyte proportions are regulated separately by different genetic elements. PMID- 11781240 TI - The different process of class switching and somatic hypermutation; a novel analysis by CD27(-) naive B cells. AB - The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27(-) naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27(-) nor cord blood B cells, which showed the unmutated Ig V-region genes, produced IgG, IgM, or IgA in response to conventional stimuli, they produced IgG and IgM but not IgA in the presence of Staphylococcus aureus Cowan strain (SAC) + interleukin-2 (IL-2) + IL 10 + anti-CD40 mAb + CD32 transfectants (CD40/CD32T). The naive B cells also produced IgE when combined with IL-4 + CD40/CD32T. In parallel with IgG production, the expression of mature gamma1 and gamma 2 transcripts was induced from naive B cells by the stimuli. The CD27 expression on human naive B cells was induced remarkably by CD40 signaling or B-cell receptor engagement, but somatic hypermutation could not be induced. The proliferation and differentiation into plasma cells were induced from naive B cells, whereas most of the plasma cells displayed very low levels of mutations in Ig V-region genes. CD27(-) naive B cells expressed activation-induced cytidine deaminase messenger RNA by the stimuli later than CD27(+) memory B cells. Our results demonstrate that CSR, but not noticeable somatic hypermutation, can be induced from CD27(-) naive B cells upon B-cell receptor engagement and CD40 signaling in cooperation with cytokines, suggesting that CSR and somatic hypermutation processes can occur independently, and the antibodies produced in this in vitro system are low-affinity antibodies. PMID- 11781241 TI - Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells. AB - The recombination activating gene-1 (RAG-1) and RAG-2 are expressed specifically in immature lymphoid cells undergoing the recombination of antigen receptor genes. The regulation of murine RAG-2 promoter was studied and it was revealed that the -41/-17 RAG-2 promoter region, which is conserved between humans and mice, was indispensable for the RAG-2 promoter activity in B-cell lines. The region contained 2 cis elements that bound c-Myb and Pax-5. Mutation in the c-Myb binding site in the promoter reduced the promoter activity in B-cell lines. Cooperative activation of the RAG-2 promoter was seen by a combination of c-Myb and Pax-5 in a human embryonic kidney cell line (293T), via their synergistic DNA binding. Deletion experiments showed that the C-terminus of c-Myb was responsible for their interaction. Furthermore, the dominant-negative c-Myb mutant suppressed the activation of the RAG-2 promoter in a pre-B-cell line as well as in 293T cells. These results suggest that cooperative binding of c-Myb and Pax-5 to the RAG-2 promoter is one of the mechanisms to direct the restricted expression of the RAG-2 in immature B cells. PMID- 11781242 TI - Tyrosine phosphorylation of B-cell adaptor for phosphoinositide 3-kinase is required for Akt activation in response to CD19 engagement. AB - CD19 is a coreceptor that amplifies signaling initiated by antigen cross-linking of the B-cell antigen receptor (BCR). CD19 can also signal independently of BCR coligation. This study shows that B-cell adaptor for phosphoinositide 3-kinase (BCAP), previously characterized as a substrate of the tyrosine kinases upon BCR engagement, is phosphorylated by cross-linking of CD19. Tyrosine phosphorylation of BCAP, mediated by Lyn, provides binding site(s) for phosphoinositide 3-kinase (PI3K), thereby participating in Akt activation. Thus, these results provide evidence that BCAP serves as an adaptor molecule for CD19 to activate the PI3K pathway in B cells. PMID- 11781243 TI - Adoptive transfer of simian immunodeficiency virus (SIV) naive autologous CD4(+) cells to macaques chronically infected with SIV is sufficient to induce long-term nonprogressor status. AB - Adoptive transfer of autologous preinfection-collected peripheral blood mononuclear cells (PBMCs) or activated CD4(+) T cells was performed in simian immunodeficiency virus (SIVmac239)-infected monkeys following short-term antiviral therapy with PMPA (9-R-[2-phosphonylmethoxypropyl] adenine). Short-term chemotherapy alone led to a transient decrease in plasma and cellular proviral DNA loads and transient rescue of gag/pol and env cytotoxic T-lymphocyte precursors (pCTLs). However, cessation of therapy allowed for SIV infection to resume its clinical course. PMPA chemotherapy coupled with infusions of either autologous pre-SIV infection-collected PBMCs or activated CD4(+) T cells led to extended control of plasma and cellular proviral DNA loads after infusion, in spite of the fact that the transfused cells were not primed against SIV. However, qualitatively different antiviral defenses were induced by infusion of unfractionated and unmanipulated PBMCs versus purified and activated CD4(+) T cells: PBMC infusions significantly favored development of SIVenv-specific pCTLs, neutralizing antibodies, and secretion of soluble noncytotoxic suppressor factors of SIV replication. In contrast, activated CD4(+) T cells predominantly promoted CTL responses to SIVgag/pol and SIVenv. In addition, infusion of influenza-primed activated CD4(+) T cells markedly enhanced influenza-specific pCTL responses, whereas infusion of similarly influenza-primed unfractionated PBMCs enhanced such pCTL responses only modestly, suggesting that the predominant immune defect after SIV infection lies in the T helper cell compartment rather than the effector cell compartment. Thus, adoptive immunotherapy with autologous "SIV naive" CD4(+) lymphocytes was sufficient to rescue cell-mediated immune responses and induce long-term anti-SIV control and immune responses in the absence of continued antiviral chemotherapy. PMID- 11781244 TI - Adenovirus type 5 vectors induce dendritic cell differentiation in human CD14(+) monocytes cultured under serum-free conditions. AB - To determine whether infection by a model virus is capable of initiating dendritic cell (DC) differentiation, human CD14(+) peripheral blood monocytes were infected with replication-defective type 5 adenovirus. Under serum-free conditions, this resulted in differentiation of a majority of cells toward a DC phenotype within 36 to 48 hours, without the need for cytokine-induced predifferentiation. Infection induced DC morphology and altered the expression of surface markers, including loss of CD14, de novo induction of CD83 and CD25, and strongly augmented expression of CD86, CD80, CD40, and HLA-DR and HLA class I molecules. Differentiated cells maintained immunophenotype without loss of viability for at least 2 days after removal of the differentiation agent and cytokines. A greatly enhanced capacity to stimulate T-lymphocyte alloproliferation and increased expression of the DC-associated transcription factor RelB were observed. Virus without transgene was found to induce changes similar to transgene-expressing viruses. RelB up-regulation and DC immunophenotype were sensitive to the antioxidant N-acetylcysteine, suggesting a critical role for nuclear factor kappaB. RNAse protection assays revealed elevated levels of messenger RNA for a number of chemokines and cytokines associated with DCs. Finally, during differentiation, adenovirus-infected monocytes were shown to secrete chemokines and cytokines, including tumor necrosis factor-alpha (TNF-alpha). Furthermore, a TNF-alpha-neutralizing antibody inhibited the expression of some DC surface markers, indicating a contributing role for this cytokine in the adenovirus-induced differentiation of DC from monocytes. These findings have implications for the biology of monocytes as precursors to DCs and also for the use of recombinant adenovirus in vaccines or gene therapy. PMID- 11781245 TI - HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas. AB - Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases characterized by a clonal accumulation of lymphocytes in the skin. Most CLs display a T(h)2 cytokine profile, including expression of interleukin-10 (IL-10). Because the up regulation of HLA-G, a nonclassical class Ib molecule inducible by IL-10, might account for the immunescape of the malignant clone, HLA-G and IL-10 expression has been investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell origin) with quantitative polymerase chain reaction (PCR) and immunohistochemistry. HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease. Except for neoplastic and infiltrating lymphocytes, other cells such as macrophages and dendritic cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which correlated with HLA-G protein presence (P <.001). HLA-G up-regulation together with IL-10 expression in CL might additionally contribute to the evasion of immunosurveillance and facilitate the transition from low- to high-grade lymphomas. PMID- 11781246 TI - Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. AB - The unique clinicopathologic features of Hodgkin lymphoma (HL) are due to the multiple cytokines produced by its neoplastic cells, the Hodgkin and Reed Sternberg (HRS) cells. Cytokine signaling is mediated through the signal transducer and activator of transcription (STAT) family of transcription factors. Immunoblotting and immunohistochemistry were used to examine cell lines and tissue sections derived from patients with HL and non-Hodgkin lymphoma (NHL) for expression of activated STAT proteins. Constitutive phosphorylation of STAT6 and STAT3 was common in HL. STAT6 was constitutively phosphorylated in 5 of 5 HL cell lines and in HRS cells from 25 of 32 (78%) classical HL cases. STAT3 was constitutively phosphorylated in 4 of 5 HL cell lines and in HRS cells from 27 of 31 (87%) classical HL cases. Only 4 of 24 NHL cases demonstrated constitutive STAT6 activation, whereas STAT3 activation was observed in 6 of 13 (46%) cases of B-cell NHL and 8 of 11 (73%) cases of T-cell NHL. Constitutive STAT5 phosphorylation was not a common feature of HL or NHL. STAT6 mediates signaling by interleukin 13 (IL-13), a cytokine frequently expressed by HRS cells. Antibody mediated neutralization of IL-13 resulted in significant decreases in both cellular proliferation and levels of phosphorylated STAT6 of HL cell lines. In conclusion, constitutive STAT6 phosphorylation is a common and distinctive feature of HRS cells in classical HL, whereas STAT3 activation was regularly present in both HL and NHL. These results suggest that IL-13 signaling is largely responsible for the constitutive STAT6 activation observed in HRS cells and further implicate IL-13 as an important growth factor in classical HL. PMID- 11781247 TI - Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. AB - Angioimmunoblastic T-cell lymphoma (AITL) is a systemic disease involving lymph nodes, spleen, and bone marrow. Although the histologic features have been well described, the diagnosis is often challenging, as there are no specific phenotypic or molecular markers available. This study shows that the neoplastic cells of AITL can be identified by aberrant CD10 expression. Archival material from 30 cases of AITL, 10 cases of peripheral T-cell lymphoma unspecified (PTL), and 10 cases of reactive lymphoid hyperplasia were reviewed. Single and double immunostaining for CD3, CD4, CD8, CD20, CD21, CD10, BCL6, Ki67, and LMP-1 in situ hybridization for Epstein-Barr early region and polymerase chain reaction (PCR) for T-cell receptor gamma chain gene and immunoglobulin heavy chain gene were performed. Three overlapping histologic patterns with hyperplastic follicles, depleted follicles, or without follicles were identified in AITL. Of the 30 cases of AITL, 27 contained CD10(+) T cells. No CD10(+) T cells were present in the cases of PTL or reactive hyperplasia. PCR confirmed a monoclonal or oligoclonal T cell population in 29 of 30 cases of AITL and a monoclonal B-cell population in 6 cases. Analysis of microdissected CD10(+) single cells showed that they belonged to the neoplastic clone. In conclusion CD10 is a phenotypic marker that specifically identifies the tumor cells in 90% of AITL, including the early cases. The presence of these cells distinguishes AITL from other PTLs. This finding provides an objective criterion for accurate and early diagnosis of AITL. PMID- 11781248 TI - Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappaB ligand on adult T-cell leukemia cells. AB - Hypercalcemia is one of the most frequent and serious complications in patients with adult T-cell leukemia (ATL) and is due to marked bone resorption by accumulation of osteoclasts (OCLs). Although several cytokines such as interleukin 1 and parathyroid hormone-related protein are thought to be involved in the development of high serum Ca(++) levels, its precise underlying mechanism remains unknown. This study analyzed the expression of various genes that are thought to regulate serum Ca(++) levels in ATL and showed that the overexpression of the receptor activator of nuclear factor kappaB (RANK) ligand gene correlated with hypercalcemia. ATL cells from patients with hypercalcemia, which highly expressed the transcripts of the RANK ligand (RANKL) gene, induced the differentiation of human hematopoietic precursor cells (HPCs) into OCLs in vitro in the presence of macrophage colony-stimulating factor (M-CSF). In contrast, ATL cells from patients without hypercalcemia did not induce such differentiation, suggesting that the induction of the differentiation correlated with the expression of the RANKL gene in ATL cells. Cell differentiation was suppressed by osteoprotegerin/Fc, an inhibitor of RANKL, indicating that such differentiation occurred through the RANK-RANKL pathway. In addition, direct contact between ATL cells and HPCs was essential for the differentiation, suggesting that not the soluble form but membrane-bound RANKL played a role in this process. These results strongly suggested that ATL cells induce the differentiation of HPCs to OCLs through RANKL expressed on their surface, in cooperation with M-CSF, and ultimately cause hypercalcemia. PMID- 11781249 TI - P-glycoprotein-actin association through ERM family proteins: a role in P glycoprotein function in human cells of lymphoid origin. AB - P-glycoprotein is a 170-kd glycosylated transmembrane protein, expressed in a variety of human cells and belonging to the adenosine triphosphate-binding cassette transporter family, whose membrane expression is functionally associated with the multidrug resistance phenotype. However, the mechanisms underlying the regulation of P-glycoprotein functions remain unclear. On the basis of some evidence suggesting P-glycoprotein-actin cytoskeleton interaction, this study investigated the association of P-glycoprotein with ezrin, radixin, and moesin, a class of proteins that cross-link actin filaments with plasma membrane in a human cell line of lymphoid origin and that have been shown to link other ion-pump related proteins. To this purpose, a multidrug-resistant variant of CCRF-CEM cells (CEM-VBL100) was used as a model to investigate the following: (1) the cellular localizations of P-glycoprotein and ezrin, radixin, and moesin and their molecular associations; and (2) the effects of ezrin, radixin, and moesin antisense oligonucleotides on multidrug resistance and P-glycoprotein function. The results showed that: (1) P-glycoprotein colocalized and coimmunoprecipitated with ezrin, radixin, and moesin; and (2) treatment with antisense oligonucleotides for ezrin, radixin, and moesin restored drug susceptibility consistently with inhibition of both drug efflux and actin-P-glycoprotein association and induction of cellular redistribution of P-glycoprotein. These data suggest that P-glycoprotein association with the actin cytoskeleton through ezrin, radixin, and moesin is key in conferring to human lymphoid cells a multidrug resistance phenotype. Strategies aimed at inhibiting P-glycoprotein actin association may be helpful in increasing the efficiency of both antitumor and antiviral therapies. PMID- 11781250 TI - The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element. AB - Cellular interleukin 6 (IL-6) is an important growth factor for Kaposi sarcoma- associated herpesvirus (KSHV)-associated neoplasms, which include human immunodeficiency virus (HIV)-related and -unrelated cases of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Increased IL-6 levels are found in tissues affected with these diseases, and KSHV exists in a latent state in the majority of virally infected cells. In addition, acute infection with KSHV up-regulates IL-6 expression in endothelial cells. Thus, the hypothesis was considered that a latent KSHV gene product up-regulates IL-6 expression. To evaluate this hypothesis, the KSHV latency-associated nuclear antigen (LANA) was expressed in human embryonal kidney 293 cells and a bone marrow stromal cell line. LANA up-regulates IL-6 expression by inducing transcription from the IL-6 promoter, and the AP1 response element within the IL 6 promoter is necessary for and mediates IL-6 up-regulation by LANA. Thus, LANA may play a key pathophysiologic role in KSHV-associated neoplasms by functioning to up-regulate expression of IL-6. PMID- 11781251 TI - Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release. AB - The purine nucleoside 2-chlorodeoxyadenosine (CdA) is often used in leukemia therapy. Its efficacy, however, is compromised by the emergence of resistant cells. In the present study, 3 CdA-resistant cell lines were generated and characterized. Their ability to accumulate 2-chloroadenosine triphosphate (CdATP) varied, reflecting differences in activities of deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Nonetheless, the selected lines were uniformly resistant to CdA-induced apoptosis, as assessed by caspase activation and DNA fragmentation. In contrast, cytosols from resistant cells were capable of robust caspase activation when incubated in the presence of cytochrome c and dATP. Moreover, replacement of dATP with CdATP also resulted in caspase activation in the parental and some of the resistant cell lines. Strikingly, CdA-induced decreases in mitochondrial transmembrane potential and release of cytochrome c from mitochondria were observed in the parental cells but not in any resistant lines. The lack of cytochrome c release correlated with an increased ability of mitochondria from resistant cells to sequester free Ca2+. Consistent with this enhanced Ca2+ buffering capacity, an early increase in cytosolic Ca2+ after CdA treatment of parental cells but not resistant cells was detected. Furthermore, CdA-resistant cells were selectively cross-resistant to thapsigargin but not to staurosporine- or Fas-induced apoptosis. In addition, CdA-induced caspase-3 activation and DNA fragmentation were inhibited by the Ca2+ chelator BAPTA-AM in sensitive cells. Taken together, the data indicate that the mechanism of resistance to CdA may be dictated by changes in Ca2+-sensitive mitochondrial events. PMID- 11781252 TI - Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. AB - The adenosine triphosphate binding-site-directed agent STI571 and the tyrphostin adaphostin are undergoing evaluation as bcr/abl kinase inhibitors. The current study compared the effects of these agents on the survival of K562 cells, bcr/abl transduced FDC-P1 cells, and myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared with healthy donors. Treatment of K562 cells with 10 microM adaphostin resulted in decreased p210(bcr/abl) polypeptide levels in the first 6 hours, followed by caspase activation and accumulation of apoptotic cells in less than 12 hours. By 24 hours, 90% of the cells were apoptotic and unable to form colonies. In contrast, 20 microM STI571 caused rapid inhibition of bcr/abl autophosphorylation without p210(bcr/abl) degradation. Although this was followed by the inhibition of Stat5 phosphorylation and the down-regulation of Bcl-x(L) and Mcl-1, only 7% +/- 3% and 25% +/- 9% of cells were apoptotic at 16 and 24 hours, respectively. Instead, the cytotoxic effects of STI571 became more pronounced with prolonged exposure, with IC90 values greater than 20 microM and 1.0 +/- 0.6 microM after 24 and 48 hours, respectively. Consistent with these results, 24-hour adaphostin exposure inhibited CML granulocyte colony-forming units (CFU-G) (median IC50, 12 microM) but not normal CFU-G (median IC50, greater than 20 microM), whereas 24-hour STI571 treatment had no effect on CML or normal CFU-G. Additional experiments revealed that STI571-resistant K562 cells remained sensitive to adaphostin. Moreover, the combination of STI571 + adaphostin induced more cytotoxicity in K562 cells and in CML CFU-G than either agent alone did. Collectively, these results identify adaphostin as a mechanistically distinct CML-selective agent that retains activity in STI571-resistant cell lines. PMID- 11781253 TI - Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils. AB - The exact mechanism of apoptosis in neutrophils (PMNs) and the explanation for the antiapoptotic effect of granulocyte colony-stimulating factor (G-CSF) in PMNs are unclear. Using specific fluorescent mitochondrial staining, immunofluorescent confocal microscopy, Western blotting, and flow cytometry, this study found that PMNs possess an unexpectedly large number of mitochondria, which are involved in apoptosis. Spontaneous PMN apoptosis was associated with translocation of the Bcl 2-like protein Bax to the mitochondria and subsequent caspase-3 activation, but not with changes in the expression of Bax. G-CSF delayed PMN apoptosis and prevented both associated events. These G-CSF effects were inhibited by cycloheximide. The general caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk) prevented caspase-3 activation and apoptosis in PMNs, but not Bax redistribution. PMN-derived cytoplasts, which lack a nucleus, granules, and mitochondria, spontaneously underwent caspase-3 activation and apoptosis (phosphatidylserine exposure), without Bax redistribution. zVAD-fmk inhibited both caspase-3 activation and phosphatidylserine exposure in cultured cytoplasts. Yet, G-CSF prevented neither caspase-3 activation nor apoptosis in cytoplasts, confirming the need for protein synthesis in the G-CSF effects. These data demonstrate that (at least) 2 routes regulate PMN apoptosis: one via Bax-to mitochondria translocation and a second mitochondria-independent pathway, both linked to caspase-3 activation. Moreover, G-CSF exerts its antiapoptotic effect in the first, that is, mitochondria-dependent, route and has no impact on the second. PMID- 11781254 TI - Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. AB - Janus kinase 3 (Jak3) is a cytoplasmic tyrosine (Tyr) kinase associated with the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)) that is activated by multiple T-cell growth factors (TCGFs) such as IL-2, -4, and -7. Using human T cells, it was found that a recently discovered variant of the undecylprodigiosin family of antibiotics, PNU156804, previously shown to inhibit IL-2-induced cell proliferation, also blocks IL-2-mediated Jak3 auto-tyrosine phosphorylation, activation of Jak3 substrates signal transducers and activators of transcription (Stat) 5a and Stat5b, and extracellular regulated kinase 1 (Erk1) and Erk2 (p44/p42). Although PNU156804 displayed similar efficacy in blocking Jak3 dependent T-cell proliferation by IL-2, -4, -7, or -15, it was more than 2-fold less effective in blocking Jak2-mediated cell growth, its most homologous Jak family member. A 14-day alternate-day oral gavage with 40 to 120 mg/kg PNU156804 extended the survival of heart allografts in a dose-dependent fashion. In vivo, PNU156804 acted synergistically with the signal 1 inhibitor cyclosporine A (CsA) and additively with the signal 3 inhibitor rapamycin to block allograft rejection. It is concluded that inhibition of signal 3 alone by targeting Jak3 in combination with a signal 1 inhibitor provides a unique strategy to achieve potent immunosuppression. PMID- 11781255 TI - HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease. AB - The HLA region has long been implicated in sporadic and familial Hodgkin disease (HD), with recent case-control studies suggesting that HLA class II loci predispose to sporadic nodular sclerosis HD (NSHD). To determine whether this predisposition extends to familial HD, HLA class II loci (DRB1, DQA1, DQB1, DRB3, DRB4, and DRB5) and transporter associated with antigen processing (TAP) loci (TAP1, TAP2) were investigated in 100 members of 16 families with at least 2 confirmed cases of HD. With the use of the transmission disequilibrium test, evidence for linkage disequilibrium with familial HD and, in particular, familial NSHD was obtained for the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, the TAP1 allele encoding Ile at residue 333, and the DRB5-0101 allele. These 3 markers were in linkage disequilibrium and may not represent independent susceptibility regions. Use of a family-based approach excludes population stratification as an explanation for these findings. PMID- 11781256 TI - PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac. AB - Fcgamma receptor-mediated phagocytosis is a model for the study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is known of the role of lipid phosphatases in the control of ITAM signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the dual-specificity phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in the signal transduction pathway leading to Fcgamma receptor IIA-mediated phagocytosis and the activation of Rac. The expression of wildtype PTEN completely abrogated the phagocytosis of immunoglobulin-G-sensitized sheep red blood cells, as compared with the catalytically inactive mutant of PTEN, which had no effect. This is the first direct evidence that PTEN, an inositol 3' phosphatase, regulates Fcgamma receptor mediated phagocytosis, an ITAM-based signaling event. The data suggest that PTEN exerts control over phagocytosis potentially by controlling the downstream conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac following ITAM stimulation. PMID- 11781257 TI - Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. AB - To assess the safety and efficacy of nonmyeloablative allogeneic transplantation in patients with HIV infection, a clinical protocol was initiated in patients with refractory hematologic malignancies and concomitant HIV infection. The results from the first 2 patients are reported. The indications for transplantation were treatment-related acute myelogenous leukemia and primary refractory Hodgkin disease in patients 1 and 2, respectively. Only patient 1 received genetically modified cells. Both patients tolerated the procedure well with minimal toxicity, and complete remissions were achieved in both patients, but patient 2 died of relapsed Hodgkin disease 12 months after transplantation. Patient 1 continues in complete remission with undetectable HIV levels and rising CD4 counts, and with both the therapeutic and control gene transfer vectors remaining detectable at low levels more than 2 years after transplantation. These results suggest that nonmyeloablative allogeneic transplantation in the context of highly active antiretroviral therapy is feasible in patients with treatment sensitive HIV infection. PMID- 11781258 TI - Severe coagulation factor V deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene. AB - A male infant with severe bleeding tendency had undetectable factor V activity. Sequence analysis of the proband's DNA revealed one base deletion in exon 13 (2952delT) and one base insertion in exon 16 (5493insG) in heterozygous form. Both mutations introduced a frameshift and a premature stop at codons 930 and 1776, respectively. The proband's father and mother were heterozygous for 2952delT and for 5493insG, respectively. Both mutations would result in the synthesis of truncated proteins lacking complete light chain or its C-terminal part. In the patient's plasma, no factor V light chain was detected by enzyme linked immunosorbent assay. The N-terminal portion of factor V containing the heavy chain, and the connecting B domain was severely reduced but detectable (1.7%). A small amount of truncated factor V-specific protein with a molecular weight ratio of 236 kd could be immunoprecipitated from the plasma and detected by Western blotting. This protein, factor V(Debrecen), corresponds to the translated product of exon 16 mutant allele. PMID- 11781259 TI - P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. AB - Human leukocytes express a receptor for extracellular nucleotides, named P2X7R, that in lymphocytes can either mediate cell death or proliferation, depending on the level of activation. The authors have investigated P2X7R expression and function in 21 patients affected by B-cell chronic lymphocytic leukemia, 13 with an evolutive and 8 with an indolent variant of the disease. Resting cytoplasmic Ca++ concentration was significantly higher in lymphocytes from patients with the evolutive compared with indolent variant. Furthermore, in the former, P2X7R stimulation triggered a Ca++ influx significantly larger. Higher Ca++ influx correlated with an increased P2X7R expression in the lymphocytes from patients with the evolutive form. Finally, incubation in the presence of extracellular adenosine triphosphate decreased spontaneous proliferation of lymphocytes from patients affected with the evolutive variant but had no effects on lymphocytes from patients with the indolent form. These results suggest that expression and function of P2X7R may correlate with the severity of B-cell chronic lymphocytic leukemia. PMID- 11781260 TI - Lentiviral gene transfer into peripheral blood-derived CD34+ NOD/SCID repopulating cells. AB - This study reports a lentiviral gene transfer protocol for efficient transduction of adult human peripheral blood (PB)-derived CD34+ NOD/SCID-repopulating cells (SRCs) using vesicular stomatitis virus-G protein (VSV-G)-pseudotyped lentiviruses encoding for enhanced green fluorescence protein (eGFP). Lentiviral stocks were concentrated by anion exchange chromatography, and transduction was performed under serum-free conditions at a multiplicity of infection (MOI) between 3 and 50. Similar transduction efficiencies were achieved in the presence and absence of cytokines. Transduction of PB-derived CD34+ cells at a MOI of 3 resulted in gene transfer efficiencies into SRCs of 9.2% and 12.0% in the absence and presence of cytokines, respectively. Using improved lentiviral vectors, transduction frequency varied between 42.0% (MOI 10) and 36.0% (MOI 50) with multilineage transgene expression within SRC-derived myeloid and lymphoid cells. The protocol described can be adapted for clinical application of lentiviral gene transfer into PB-derived CD34+ cells from adult patients. PMID- 11781261 TI - Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571. AB - Despite the efficacy of STI571 (Glivec, Novartis, Basle, Switzerland) in treating chronic myeloid leukemia (CML), drug resistance has already been noted both in vitro and in vivo. As plasma proteins, including alpha-1-acid glycoprotein (AGP), may reduce drug efficacy through binding, AGP was investigated for its ability to interact with STI571. At all stages of CML, AGP plasma level was significantly higher than in normal controls (P <.05). The glycoprotein was purified from normal plasma and individual chronic myeloid leukemia (CML) patients' plasma by low-pressure chromatography. The influence of alpha1-acid glycoprotein (AGP), in the presence of STI571, on the proliferation of Philadelphia chromosome-positive (Ph+) cells was examined. Normal AGP, even at supraphysiological concentrations, did not block the effect of STI571 on K562-cell proliferation in vitro. Moreover, CML-derived AGP failed to block the effect of STI571 on Ph+ cells in vitro. Thus, these in vitro findings suggest that AGP will not abrogate the antileukemic activity of STI571. PMID- 11781262 TI - Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells. AB - With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (S(mu)) region instead of the J(H) or D(H) gene segments was identified. Sequence analysis showed that the genomic breakpoint is localized between the S(mu) region of the IGH complex and the first intron of BCL2. Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site I(mu). Sequence analysis of the V(H) region of the functional nontranslocated IGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center. This is the first example of a t(14;18) translocation that results from an illegitimate IGH class switch recombination during the germinal center B-cell stage. PMID- 11781263 TI - Human hematopoiesis in murine embryos after injecting human cord blood-derived hematopoietic stem cells into murine blastocysts. AB - At different developmental stages, candidate human hematopoietic stem cells (HSCs) are present within the CD34+ CD38- population. By means of xenotransplantation, such CD34+CD38- cells were recently shown to engraft the hematopoietic system of fetal sheep and nonobese diabetic severe combined immunodeficient adult mice. Here it is demonstrated that, after their injection into murine blastocysts, human cord blood (CB)-derived CD34+ and CD34+ CD38- cells repopulate the hematopoietic tissues of nonimmunocompromised murine embryos and that human donor contribution can persist to adulthood. It is further observed that human hematopoietic progenitor cells are present in murine hematopoietic tissues of midgestational chimeric embryos and that progeny of the injected human HSCs activate erythroid-specific gene expression. Thus, the early murine embryo provides a suitable environment for the survival and differentiation of human CB CD34+ CD38- cells. PMID- 11781264 TI - Chlamydia pneumoniae and atherosclerosis: critical assessment of diagnostic methods and relevance to treatment studies. AB - A number of studies have found that inflammation of the vessel wall plays an essential role in both the initiation and progression of atherosclerosis and erosion and fissure and the eventual rupture of plaques. Chlamydia pneumoniae is one of the infectious agents that have been investigated as possible causes of this inflammation. Initial studies of the association of C. pneumoniae and cardiovascular disease (CVD) were seroepidemiologic, and these were followed by studies in which the organism was identified in vascular tissue from patients with CVD by electron microscopy, PCR and immunocytochemical staining (ICC). C. pneumoniae has also been isolated by culture from vascular tissue in a small number patients. However, no single serologic, PCR, or ICC assay has been used consistently across all studies. The assays used are also not standardized. Recent studies of serologic and PCR assays for diagnosis of C. pneumoniae infection have suggested that there may be substantial interlaboratory variation in the performance of these tests. It now appears that some of the inconsistency of results from study to study may be due, in part, to lack of standardized methods. Although initial seroepidemiologic studies demonstrated a significantly increased risk of adverse cardiac outcome in patients who were seropositive, subsequent prospective studies found either small or no increased risk. In addition to the lack of consistent serologic criteria, recent evaluations have demonstrated inherent problems with performance of the most widely used serologic methods. Most importantly, we do not have a reliable serologic marker for chronic or persistent C. pneumoniae infection. PMID- 11781266 TI - Recent advances in biology and immunobiology of Eimeria species and in diagnosis and control of infection with these coccidian parasites of poultry. AB - Avian coccidiosis, an intestinal disease caused by protozoan parasites of the genus Eimeria, occurs worldwide. It is considered to be one of the most economically important diseases of domestic poultry. For many years, prophylactic use of anticoccidial feed additives has been the primary means of controlling coccidiosis in the broiler industry and has played a major role in the growth of this industry, which now can produce about 7.6 billion chickens annually. However, development of anticoccidial resistance has threatened the economic stability of the broiler industry. Although there has been little effort by the pharmaceutical industry to develop new anticoccidials, the mounting problem of drug resistance of Eimeria species has prompted major research efforts to seek alternative means of control through increased knowledge of parasite biology, host response, and nutritional modulation. As a consequence, important advancements have been made, particularly in defining parasite antigens that have potential use in vaccines, defining the Eimeria genome, understanding the immunology of coccidial infections, and the practical applications of live vaccines. This review describes the progress in these areas, most of which has occurred within the past 10 to 15 years. PMID- 11781267 TI - Rapid diagnostic tests for malaria parasites. AB - Malaria presents a diagnostic challenge to laboratories in most countries. Endemic malaria, population movements, and travelers all contribute to presenting the laboratory with diagnostic problems for which it may have little expertise available. Drug resistance and genetic variation has altered many accepted morphological appearances of malaria species, and new technology has given an opportunity to review available procedures. Concurrently the World Health Organization has opened a dialogue with scientists, clinicians, and manufacturers on the realistic possibilities for developing accurate, sensitive, and cost effective rapid diagnostic tests for malaria, capable of detecting 100 parasites/microl from all species and with a semiquantitative measurement for monitoring successful drug treatment. New technology has to be compared with an accepted "gold standard" that makes comparisons of sensitivity and specificity between different methods. The majority of malaria is found in countries where cost-effectiveness is an important factor and ease of performance and training is a major consideration. Most new technology for malaria diagnosis incorporates immunochromatographic capture procedures, with conjugated monoclonal antibodies providing the indicator of infection. Preferred targeted antigens are those which are abundant in all asexual and sexual stages of the parasite and are currently centered on detection of HRP-2 from Plasmodium falciparum and parasite-specific lactate dehydrogenase or Plasmodium aldolase from the parasite glycolytic pathway found in all species. Clinical studies allow effective comparisons between different formats, and the reality of nonmicroscopic diagnoses of malaria is considered. PMID- 11781265 TI - Immunology of diseases associated with Malassezia species. AB - Malassezia species are members of the human cutaneous commensal flora, in addition to causing a wide range of cutaneous and systemic diseases in suitably predisposed individuals. Studies examining cellular and humoral immune responses specific to Malassezia species in patients with Malassezia-associated diseases and healthy controls have generally been unable to define significant differences in their immune response. The use of varied antigenic preparations and strains from different Malassezia classifications may partly be responsible for this, although these problems can now be overcome by using techniques based on recent work defining some important antigens and also a new taxonomy for the genus. The finding that the genus Malassezia is immunomodulatory is important in understanding its ability to cause disease. Stimulation of the reticuloendothelial system and activation of the complement cascade contrasts with its ability to suppress cytokine release and downregulate phagocytic uptake and killing. The lipid-rich layer around the yeast appears to be pivotal in this alteration of phenotype. Defining the nonspecific immune response to Malassezia species and the way in which the organisms modulate it may well be the key to understanding how Malassezia species can exist as both commensals and pathogens. PMID- 11781268 TI - Clinical aspects and pathophysiology of inflammatory bowel disease. AB - The chronic inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are recognized as important causes of gastrointestinal disease in children and adults. In this review we delineate the clinical manifestations and diagnostic features of IBD. In addition, we summarize important recent advances in our understanding of the immune mediators of intestinal inflammation. This information has led to new therapeutic approaches in IBD. Further, we discuss the considerable data that point to the significance of genetic factors in the development of IBD and the genetic loci which have been implicated through genome wide searches. The commensal bacterial flora also appears to be a critical element, particularly in regards to Crohn's disease, although the precise role of the bacteria in the disease manifestations remains unclear. Current investigations promise to yield fresh insights in these areas. PMID- 11781269 TI - Modulation of release of proinflammatory bacterial compounds by antibacterials: potential impact on course of inflammation and outcome in sepsis and meningitis. AB - Several bacterial components (endotoxin, teichoic and lipoteichoic acids, peptidoglycan, DNA, and others) can induce or enhance inflammation and may be directly toxic for eukaryotic cells. Bactericidal antibiotics which inhibit bacterial protein synthesis release smaller quantities of proinflammatory/toxic bacterial compounds than B-lactams and other cell wall-active drugs. Among the B lactams, compounds binding to penicillin-binding protein 2 (PBP-2) release smaller amounts of bacterial substances than antibacterials inhibiting PBP-3. Generally, high antibiotic concentrations (more than 10 times the MIC) induce the release of fewer bacterial proinflammatory/toxic compounds than concentrations close to the MIC. In several in vitro and in vivo systems, bacteria treated with protein synthesis inhibitors or B-lactams inhibiting PBP-2 induce less inflammation than bacteria treated with PBP-3-active B-lactams. In mouse models of Escherichia coli peritonitis sepsis and of Streptococcus pneumoniae meningitis, lower release of proinflammatory bacterial compounds was associated with reduced mortality. In conclusion, sufficient evidence for the validity of the concept of modulating the release of proinflammatory bacterial compounds by antibacterials has been accumulated in vitro and in animal experiments to justify clinical trials in sepsis and meningitis. A properly conducted study addressing the potential benefit of bacterial protein synthesis inhibitors versus B-lactam antibiotics will require both strict selection and inclusion of a large number of patients. The benefit of this approach should be greatest in patients with a high bacterial load. PMID- 11781270 TI - Bacterial endophthalmitis: epidemiology, therapeutics, and bacterium-host interactions. AB - Endophthalmitis is a severe inflammation of the interior of the eye caused by the introduction of contaminating microorganisms following trauma, surgery, or hematogenous spread from a distant infection site. Despite appropriate therapeutic intervention, bacterial endophthalmitis frequently results in visual loss, if not loss of the eye itself. Although the pathogenicity of bacterial endophthalmitis has historically been linked with toxin production during infection, a paucity of information exists as to the exact mechanisms of retinal toxicity and the triggers for induction of the intraocular immune response. Recently, research has begun to examine the bacterial and host molecular and cellular events that contribute to ocular damage during endophthalmitis. This review focuses on the causative agents and therapeutic challenges of bacterial endophthalmitis and provides current data from the analysis of the role of bacterial virulence factors and host inflammatory interactions in the pathogenesis of eye infections. Based on these and related studies, a hypothetical model for the molecular pathogenesis of bacterial endophthalmitis is proposed. Identifying and understanding the basic mechanisms of these bacterium host interactions will provide the foundation for which novel, information-based therapeutic agents are developed in order to prevent vision loss during endophthalmitis. PMID- 11781273 TI - Fecal incontinence: a neglected area of gastroenterology. PMID- 11781272 TI - Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients. AB - Cryptosporidium spp. are a major cause of diarrheal disease in both immunocompetent and immunodeficient individuals. They also cause waterborne disease in both the United States and United Kingdom. Studies on the mechanisms of immunity to cryptosporidiosis indicate the importance of the T-cell response. The spectrum and severity of disease in immunocompromised individuals with cryptosporidiosis reflect this importance since the most severe disease is seen in individuals with defects in the T-cell response. The most commonly studied group is that of patients with AIDS. These patients suffer from more severe and prolonged gastrointestinal disease that can be fatal; in addition, body systems other than the gastrointestinal tract may be affected. The widespread use of antiretroviral therapy does appear to be having a beneficial effect on recovery from cryptosporidiosis and on the frequency of infection in human immunodeficiency virus-positive patients. Other diseases that are associated with increased risk of severe cryptosporidiosis, such as primary immunodeficiencies, most notably severe combined immunodeficiency syndrome, are also predominantly associated with T-cell defects. Of the remaining groups, children with acute leukemia seem to be most at risk from cryptosporidiosis. There is less evidence of severe complications in patients with other malignant diseases or in those receiving immunosuppressive chemotherapy. PMID- 11781271 TI - Moraxella catarrhalis: from emerging to established pathogen. AB - Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of B-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen. PMID- 11781274 TI - Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. AB - BACKGROUND & AIMS: We investigated if inhibition of mitogen-activated protein kinases (MAPKs) was beneficial in Crohn's disease. METHODS: Inhibition of JNK and p38 MAPK activation with CNI-1493, a guanylhydrazone, was tested in vitro. Twelve patients with severe Crohn's disease (mean baseline, CDAI 380) were randomly assigned to receive either 8 or 25 mg/m(2) CNI-1493 daily for 12 days. Clinical endpoints included safety, Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire, and the Crohn's Disease Endoscopic Index of Severity. RESULTS: Colonic biopsies displayed enhanced JNK and p38 MAPK activation. CNI-1493 inhibition of both JNK and p38 phosphorylation was observed in vitro. Treatment resulted in diminished JNK phosphorylation and tumor necrosis factor production as well as significant clinical benefit and rapid endoscopic ulcer healing. No serious adverse events were noted. A CDAI decrease of 120 at week 4 (P = 0.005) and 146.5 at week 8 (P = 0.005) was observed. A clinical response was seen in 67% of patients at 4 weeks and 58% at 8 weeks. Clinical remission was observed in 25% of patients at week 4 and 42% at week 8. Endoscopic improvement occurred in all but 1 patient. Response was seen in 3 of 6 infliximab failures, 2 of whom showed remission. Fistulae healing occurred in 4 of 5 patients, and steroids were tapered in 89% of patients. CONCLUSIONS: Inflammatory MAPKs are critically involved in the pathogenesis of Crohn's disease and their inhibition provides a novel therapeutic strategy. PMID- 11781275 TI - Ulcerative colitis: female fecundity before diagnosis, during disease, and after surgery compared with a population sample. AB - BACKGROUND & AIMS: Women with ulcerative colitis generally have normal fertility. The aim of this study was to compare patients' fecundability before and after restorative proctocolectomy with ileal pouch-anal anastomosis with the fecundability of the general population. METHODS: Historical follow-up was performed on 343 consecutive female patients aged 10.6-40.5 years at surgery and a reference population of 1200 women aged 25-40 years. A total of 290 (85%) patients and 661 (55%) women in the reference population agreed to participate in a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. Cox regression and Kaplan-Meier plots were used for analysis. RESULTS: Surgery significantly reduced the ratio of patient to reference population fecundability, which decreased to 0.20 (P < 0.0001). Before diagnosis and from diagnosis until colectomy, the fecundability of the patients was similar to that of the reference population. CONCLUSIONS: Female patients with ulcerative colitis have normal fecundity before surgical treatment. Surgery severely reduces female fecundity. Information about this reduction in fecundity should be given before surgery, and if a woman has an unfulfilled wish for pregnancy after surgery, early referral to a gynecologist is recommended. PMID- 11781276 TI - Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. AB - BACKGROUND & AIMS: Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC. METHODS: Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8 week period; responders discontinued treatment and were followed up. RESULTS: Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001). CONCLUSIONS: Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria. PMID- 11781277 TI - Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review. AB - BACKGROUND & AIMS: The public health impact of past screening and surveillance practices on the outcomes of Barrett's related cancers has not previously been quantified. Our purpose was to determine the prior prevalence of Barrett's esophagus in reported cases of incident adenocarcinoma undergoing resection, as an indirect measure of impact. METHODS: We performed a systematic review of the literature from 1966 to 2000. Studies were included if they reported: (1) the number of consecutive adenocarcinomas resected, and (2) the number of those resected who had a previously known diagnosis of Barrett's. We generated summary estimates using a random effects model. RESULTS: We identified and reviewed 752 studies. Twelve studies representing a total of 1503 unique cases of resected adenocarcinomas met inclusion criteria. Using a random effects model, the overall percentage of patients undergoing resection who had a prior diagnosis of Barrett's was 4.7% +/- 2.9%. CONCLUSIONS: The low prior prevalence (approximately 5%) of Barrett's esophagus in this study population provides indirect evidence to suggest that recent efforts to identify patients with Barrett's-whether through endoscopic screening or evaluation of symptomatic patients-have had minimal public health impact on esophageal adenocarcinoma outcomes. The potential benefits of endoscopic surveillance seem to have been limited to only a fraction of those individuals at risk. These data thus provide a clear and compelling rationale for the development of effective screening strategies to identify patients with Barrett's esophagus. PMID- 11781278 TI - Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. AB - BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreas has attracted increasing interest because of its unique presentation. The differential diagnosis between malignant and benign tumors is extremely important in the determination of the therapy for IPMT. The aims of this study are to determine the usefulness of peroral pancreatoscopy (POPS) and intraductal ultrasonography (IDUS) in IPMT for the differentiation of malignant from benign disease, and to evaluate the significance of these techniques as new preoperative examinations. METHODS: Sixty histopathologically confirmed patients with IPMT underwent POPS and/or IDUS preoperatively. POPS was perfomed in all patients, and IDUS in 40. Findings of POPS and IDUS were compared with histopathology of resected specimens. The postoperative follow-up data were analyzed. RESULTS: Protruding lesions were detected by POPS in 40 patients. They were classified into 5 groups. Fish-egg-like type with vascular images, villous type, and vegetative type were considered to be malignant. By IDUS, lesions protruding 1 mm or more were observed in 36 patients. Of the lesions protruding 4 mm or more, 88% were malignant. Combination of POPS and IDUS improved the differential diagnosis between benign and malignant IPMT. The 3-year cumulative survival rate and disease-free survival rate were extremely high at 95% and 93%, respectively. CONCLUSIONS: The combination of POPS and IDUS results in a considerably improved differential diagnosis between malignant and benign IPMT and is useful for determining an effective therapeutic approach. These new techniques can contribute to improvements in postoperative results. PMID- 11781279 TI - Mucosal flora in inflammatory bowel disease. AB - BACKGROUND & AIMS: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. METHODS: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. RESULTS: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/microL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/microL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. CONCLUSIONS: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD. PMID- 11781280 TI - Gastroesophageal reflux disease in monozygotic and dizygotic twins. AB - BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) interferes with the quality of life and carries an increased risk for esophageal adenocarcinoma. We investigated genetic influence in the development of reflux. METHODS: We compared concordance for reflux in monozygotic (MZ) and dizygotic (DZ) twins. All twins age 55 and older in the nationwide Swedish Twin Registry were invited to participate. Data were collected by computer-assisted telephone interviews. Reflux disease was defined by symptomatic heartburn or acid regurgitation occurring at least weekly. RESULTS: A total of 2178 monozygotic, 3219 same-sex dizygotic, and 3014 unlike-sex dizygotic twin pairs provided information. Overall, 15.3% of the twins had reflux. In men, the intraclass correlation for reflux was 0.29 (95% confidence interval [CI], 0.15-0.43) for monozygotic and 0.13 (95% CI, 0.02-0.25) for dizygotic pairs. In women, the correlation was 0.33 (95% CI, 0.22-0.44) for monozygotic and 0.14 (95% CI, 0.04-0.24) for dizygotic pairs. For unlike-sex dizygotic pairs, the correlation was 0.06 (95% CI, -0.01 to 0.14). Concordance for reflux was not caused by inherited obesity or alcohol use; inherited smoking may be a minor factor. CONCLUSIONS: The increased concordance for reflux in monozygotic pairs, compared with dizygotic pairs, indicates genetic rather than shared environmental effects. Heritability accounted for 31% (23% 39%) of the liability to reflux disease in this population. PMID- 11781281 TI - Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. AB - BACKGROUND & AIMS: Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules. METHODS: In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival. RESULTS: We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P = 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors. CONCLUSIONS: Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate. PMID- 11781282 TI - Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. AB - BACKGROUND & AIMS: The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease. METHODS: All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993. RESULTS: Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000. CONCLUSIONS: Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma. PMID- 11781283 TI - Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis. AB - BACKGROUND & AIMS: The aim of the study is to compare the cost-effectiveness of aspirin and colonoscopy in the prevention of colorectal cancer. METHODS: A Markov process is used to follow a hypothetical cohort of 100,000 subjects aged 50 years until death. Four strategies are compared: (1) no intervention, (2) colonoscopy once per 10 years and every 3 years in subjects with polyps, (3) chemoprevention with 325 mg of daily aspirin, and (4) combination of the second and third strategies. The various strategies are compared calculating incremental cost effectiveness ratios (ICERs). RESULTS: The expected number of colorectal cancers is 5904 per 100,000 subjects. Colonoscopy prevents 4428 colorectal cancers and saves 7951 life-years at an ICER of $10,983 per life-year saved compared with no intervention. Aspirin prevents 2952 colorectal cancers and saves 5301 life-years at an ICER of $47,249 per life-year saved compared with no intervention. The cost of aspirin therapy plus management of aspirin-related complications was reported to be $172 per year per patient. Varying the annual aspirin-related costs between $50 and $200 results in ICER changes between $4617 and $57,080, with the 2 strategies breaking even at $70. Applying aspirin chemoprevention plus colonoscopy screening concomitantly yields an ICER of $227,607 per life-year saved compared with screening colonoscopy alone. CONCLUSION: As compared with colonoscopy once per 10 years, the use of aspirin to prevent colorectal cancer saves fewer lives at higher costs. The high complication cost and the lower efficacy of aspirin render screening colonoscopy a more cost-effective strategy to prevent colorectal cancer. PMID- 11781284 TI - Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. AB - BACKGROUND & AIMS: Recent studies have described the existence of endogenous cannabinoids with vasodilator activity because of their interaction with peripheral CB1 receptors, anandamide being the most extensively investigated. The study investigated whether endogenous cannabinoids are involved in the pathogenesis of the cardiovascular disturbances in experimental cirrhosis. METHODS: Arterial pressure, cardiac output, and total peripheral resistance were measured before and after the administration of a cannabinoid CB1 receptor antagonist to cirrhotic rats with ascites and to control rats. Blood pressure was also assessed in normotensive recipient rats after the intravenous administration of blood cells or isolated monocytes obtained from cirrhotic and control rats. Moreover, the endogenous content of anandamide was measured in circulating monocytes of cirrhotic and control rats by gas chromatography/mass spectrometry. RESULTS: CB1 receptor blockade did not modify systemic hemodynamics in control rats, but significantly increased arterial pressure and peripheral resistance in cirrhotic animals. Blood cell suspension or monocytes from cirrhotic animals, but not from controls, induced arterial hypotension in recipient rats. Finally, anandamide was solely detected in monocytes of cirrhotic animals. CONCLUSIONS: Monocytes of cirrhotic rats with ascites are activated to produce anandamide and this substance contributes to arterial hypotension in experimental cirrhosis. PMID- 11781285 TI - Distinct inflammatory mechanisms mediate early versus late colitis in mice. AB - BACKGROUND & AIMS: Progression from the acute to chronic phase of inflammatory bowel disease cannot be easily evaluated in patients and has not been characterized in animal models. We report a longitudinal study investigating changes in the mucosal immune response in an experimental model of colitis. METHODS: Severity of colitis, body mass, stool consistency and blood content, serum amyloid A, and tissue histology were examined in interleukin (IL)-10 deficient mice over 35 weeks. The corresponding production of IL-12, IL-18, interferon gamma, tumor necrosis factor alpha, IL-4, and IL-13 by lamina propria mononuclear cells in the inflamed intestine was measured. Administration of neutralizing antibody to IL-12 at distinct times during disease progression permitted evaluation of its therapeutic potential. RESULTS: The clinical manifestations and intestinal inflammation delineated an early phase of colitis (10-24 weeks), characterized by a progressive increase in disease severity, followed by a late phase (>25 weeks), in which chronic inflammation persisted indefinitely. Lamina propria mononuclear cells from mice with early disease synthesized progressively greater quantities of IL-12 and interferon gamma, whereas production of both cytokines dramatically declined and returned to pre disease levels in the late phase of colitis. Consistent with this pattern, neutralizing antibody to IL-12 reversed early, but not late, disease. In contrast, IL-4 and IL-13 production increased progressively from pre- to early to late disease. CONCLUSIONS: Colitis that develops in IL-10-deficient mice evolves into 2 distinct phases. IL-12 plays a pivotal role in early colitis, whereas its absence and the synthesis of IL-4 and IL-13 in late disease indicate that other immune mechanisms sustain chronic inflammation. PMID- 11781286 TI - Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats. AB - BACKGROUND & AIMS: Ethanol metabolism by pancreatic acinar cells and the role of its metabolites in ethanol toxicity to the pancreas remain largely unknown. Here, we characterize ethanol metabolism in pancreatic acinar cells and determine the effects of ethanol metabolites on nuclear factor kappa B (NF-kappa B) and activator protein (AP)-1, transcription factors that are activated in pancreatitis and mediate expression of inflammatory molecules critical for this disease. METHODS: We measured activities of fatty acid ethyl ester (FAEE) synthase and alcohol dehydrogenase (ADH), as well as accumulation of ethanol metabolites. We measured the effects of ethanol and its metabolites on NF-kappa B and AP-1 activation by using a gel shift assay. RESULTS: Pancreas metabolizes ethanol via both oxidative and nonoxidative pathways. Acinar cells are the main source of ethanol metabolism in the pancreas. Compared with the liver, FAEE synthase activity in the pancreas is greater, whereas that of ADH is much less. FAEEs activated NF-kappa B and AP-1, whereas acetaldehyde inhibited NF-kappa B activation. Ethanol decreased NF-kappa B binding activity in acinar cells, which was potentiated by cyanamide. CONCLUSION: Oxidative and nonoxidative ethanol metabolites regulate transcription factors differently in pancreatic acinar cells. Ethanol may regulate NF-kappa B and AP-1 positively or negatively, depending on which metabolic pathway's effect predominates. These regulatory mechanisms may play a role in ethanol toxicity to the pancreas. PMID- 11781287 TI - Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice. AB - BACKGROUND & AIMS: Reduced gastric acid predisposes the stomach to colonization by bacteria and inflammation. Therefore, we investigated how the chronic gastritis in mice made hypochlorhydric by either gastrin deficiency or omeprazole treatment modulates epithelial cell function. METHODS: The gastric pathology of 16-week-old wild-type gastrin-expressing (G+/+) and gastrin-deficient (G-/-) mice maintained in conventional housing was compared. G-/- mice were then treated with antibiotics for 20 days. In a separate experiment, G+/+ mice were treated with omeprazole for 2 months or treated with omeprazole and antibiotics. RESULTS: Compared with the G+/+ animals, the hypochlorhydric G-/- mice showed significant inflammation that resolved after 20 days of antibiotic treatment and correlated with a decrease in bacterial overgrowth. Elevated G- and parietal-cell numbers in the G-/- mice, quantified by flow cytometry, normalized after antibiotic treatment. G+/+ mice treated with omeprazole had increased bacteria and mucosal lymphocytes that resolved after antibiotic therapy. Quantitation of the gastric cells in these omeprazole-treated mice revealed a significant increase in G- and parietal-cell numbers. On resolution of the gastritis, a decrease in parietal and gastrin-expressing (G) cells was observed despite sustained hypochlorhydria in the presence of omeprazole. CONCLUSIONS: Genetic or chemical hypochlorhydria predisposes the stomach to bacterial overgrowth resulting in inflammation. The specific changes in parietal and G cells correlate with the presence of inflammation and not directly with gastric acid. Thus, the normal stomach responds to inflammation by increasing the number and function of cell types that are able to maximize gastric acid output. PMID- 11781288 TI - Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. AB - BACKGROUND & AIMS: Tumor necrosis factor (TNF) induces multiple effects including cell proliferation and death by ligation with TNF receptor type II (TNFR2). We studied the role of TNFR2 in chronic inflammation-induced colonic epithelial alteration. METHODS: TNFR2 expression in colonic epithelial cells (CECs) was assessed by ribonuclease protection assay (RPA) and immunohistochemistry (IHC) in patients with inflammatory bowel disease (IBD) and murine colitis models. TNFR2 expression was also analyzed using COLO205 cells. The role of TNFR2 in colonic epithelial homeostasis was examined by generating interleukin 6-deficient TCR alpha KO (alpha IL-6DKO) or TNFR2-deficient TCR alpha (alpha TNFR2DKO) mice. RESULTS: TNFR2 expression was up-regulated in CEC in both human ulcerative colitis and Crohn's disease. In vitro studies showed that TNFR2 expression was up regulated by a cooperative effect of key proinflammatory cytokines. By RPA, the increased expression of TNFR2 was detectable in TCR alpha KO mice with colitis compared with TCR alpha KO mice without colitis or wild-type mice. In alpha IL 6DKO mice, TNFR2 expression, proliferation, and nuclear factor kappa B activation of CECs were markedly reduced compared with TCR alpha KO mice. alpha TNFR2 mice also showed significantly less colonic epithelial proliferation compared with TCR alpha KO mice. CONCLUSIONS: Expression of TNFR2 is consistently increased on CECs in both murine colitis models as well as patients with IBD. TNFR2 may play an important role in colonic inflammation-associated alteration in the intestinal epithelium. PMID- 11781289 TI - Gastric acid secretion in L-histidine decarboxylase-deficient mice. AB - BACKGROUND & AIMS: Histamine, gastrin, and acetylcholine are known to be the primary secretagogues of gastric acid secretion, but how the roles are shared among these secretagogues remains to be fully clarified. To evaluate the cooperation between histamine and the other secretagogues, acid secretion responses induced by each secretagogue were measured in L-histidine decarboxylase (HDC)-deficient mice. METHODS: Acid secretion was measured by the titration of acid under anesthesia. The expression of selected genes involved in acid secretion was determined by Northern blot and/or immunoblot analysis. Histamine-2 (H(2)) receptor binding in the gastric mucosa was investigated using [(3)H]tiotidine. RESULTS: HDC-deficient mice showed low basal and high exogenous histamine-stimulated acid secretion. The mutant mice showed hypergastrinemia and did not undergo acid secretion upon treatment with exogenous gastrin. However, carbachol stimulated weak and transient acid secretion in the mutants. The Bmax values for H(2) and the expression of Gs alpha in gastric mucosal membranes were higher in the mutants than in the wild-type mice. CONCLUSIONS: This study confirms the concept that histamine production is essential for gastric acid secretion induced by gastrin, but not for that induced by carbachol. HDC deficient mice should be a suitable model for further functional analyses of the correlation between histamine and the other acid secretagogues. PMID- 11781290 TI - Thermal stress-induced HSP70 mediates protection against intrapancreatic trypsinogen activation and acute pancreatitis in rats. AB - BACKGROUND & AIMS: Prior thermal stress induces heat shock protein 70 (HSP70) expression in the pancreas and protects against secretagogue-induced pancreatitis, but it is not clear that this thermal stress-induced protection is actually mediated by HSP70 since thermal stress may have other, non-HSP related, effects. METHODS: In the present study, we have administered antisense (AS) oligonucleotides, which prevent pancreatic expression of HSP70 to rats, in vivo, to evaluate this issue. In a separate series of experiments, designed to examine the role of pancreatitis-induced HSP70 expression in modulating the severity of pancreatitis, rats not subjected to prior thermal stress were given AS-HSP70 before cerulein administration, and trypsinogen activation as well as the severity of pancreatitis were evaluated. RESULTS: Hyperthermia induced HSP70 expression, prevented intrapancreatic trypsinogen activation, and protected against cerulein-induced pancreatitis. Administration of AS-HSP70 but not sense HSP70 reduced the thermal stress-induced HSP70 expression, restored the ability of supramaximal cerulein stimulation to cause intrapancreatic trypsinogen activation, and abolished the protective effect of prior thermal stress against pancreatitis. In non-thermally stressed animals, pretreatment with AS-HSP70 before the induction of pancreatitis exacerbated all the parameters associated with pancreatitis. CONCLUSIONS: These findings lead us to conclude that HSP70 induction, rather than some other thermal stress-related phenomenon, mediates the thermal stress-induced protection against pancreatitis and that it protects against pancreatitis by preventing intrapancreatic activation of trypsinogen. The worsening of pancreatitis, which occurs when non-thermally stressed animals are given AS-HSP70 before cerulein, suggests that cerulein-induced HSP70 expression in nontreated animals acts to limit the severity of pancreatitis. PMID- 11781291 TI - Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells. AB - BACKGROUND & AIMS: In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells. METHODS: CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappa B and p53 activation was assessed by electromobility shift assays. RESULTS: Fractalkine mediated the MEK-1 and G alpha i-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappa B and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1 mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithelial cell monolayer. CONCLUSIONS: CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium. PMID- 11781292 TI - Sodium current in human jejunal circular smooth muscle cells. AB - BACKGROUND & AIMS: Sodium channels are key regulators of neuronal and muscle excitability. However, sodium channels have not been definitively identified in gastrointestinal smooth muscle. The aim of the present study was to determine if a Na(+) current is present in human jejunal circular smooth muscle cells. METHODS: Currents were recorded from freshly dissociated cells using patch-clamp techniques. Complementary DNA (cDNA) libraries constructed from the dissociated cells were screened to determine if a message for alpha subunits of Na(+) channels was expressed. Smooth muscle cells were also collected using laser capture microdissection and screened. RESULTS: A tetrodotoxin-insensitive Na(+) channel was present in 80% of cells patch-clamped. Initial activation was at -65 mV with peak inward current at -30 mV. Steady-state inactivation and activation curves revealed a window current between -75 and -60 mV. The Na(+) current was blocked by lidocaine and internal and external QX314. A cDNA highly homologous to SCN5A, the alpha subunit of the cardiac Na(+) channel, was present in the cDNA libraries constructed from dissociated cells and from smooth muscle cells collected using laser-capture microdissection. CONCLUSIONS: Human jejunal circular smooth muscle cells express a tetrodotoxin-insensitive Na(+) channel, probably SCN5A. Whether SCN5A plays a role in the pathophysiology of human gut dysmotilities remains to be determined. PMID- 11781293 TI - Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat. AB - BACKGROUND & AIMS: In pancreatitis-associated lung injury, neutrophils (PMN) access the lung by migration through endothelial basement membranes. We hypothesize that degeneration of the basement membrane by specific PMN-produced matrix metalloproteinases (MMPs) may facilitate this process. METHODS: Mild or severe pancreatitis was induced in rats and the consequent pulmonary injury characterized. MMP-2 and MMP-9 activity in supernatant of PMN cultures and homogenates of lungs were assessed by zymography and Western blot. Congruence of PMN and MMP expression in lung tissue was evaluated by neutrophil depletion and fluorescent immunohistochemistry (IHC). The contribution of MMPs to PMN transmigration and lung injury was tested with the MMP inhibitor batimastat (BB 94) in vitro (PMN transmigration across matrigel chambers) and in vivo (myeloperoxidase activity and Evans blue in broncho-alveolar lavage fluid). RESULTS: MMP-9 was highly expressed in lungs and supernatant of neutrophil cultures in severe pancreatitis, and, to a lesser degree, in mild pancreatitis. Lung IHC showed colocalization of MMP-9 and PMN. PMN depletion simultaneously reduced neutrophil infiltration and MMP-9 levels in lung tissue. Trypsin, interleukin 1 beta, and tumor necrosis factor (TNF)-alpha all potently stimulated MMP-9 release from PMN. BB-94 significantly reduced TNF-alpha-induced PMN transmigration across matrigel and ameliorated transendothelial PMN migration and protein leak in severe pancreatitis. CONCLUSIONS: MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity. MMP inhibition reduces PMN transmigration and reduces resultant alveolar-capillary leakage. These findings suggest an important role for MMP-9 from PMN in the pathogenesis of pancreatitis-associated lung injury. PMID- 11781294 TI - Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. AB - BACKGROUND & AIMS: Apoptosis of hepatocytes is a central feature of ischemic injury in the liver. The aim of this study was to identify extracellular inducers of apoptosis in the murine ischemic liver. METHODS: Involvement of tumor necrosis factor (TNF)-alpha and Fas signaling was evaluated using various knockout mice (TNF-receptor 1 [TNF-R1]-/-, Fas[lpr]-/-, and Fas ligand[gld]-/-) and wild-type mice pretreated with pentoxifylline, an inhibitor of TNF-alpha synthesis. RESULTS: Expression of TNF-alpha was increased after ischemia and reperfusion in wild-type mice and TNF-R1-deficient mice when compared with sham-operated animals. Pentoxifylline prevented up-regulation of TNF-alpha expression. Inhibition of TNF-alpha resulted in significant decrease of serum aspartate aminotransferase levels and prolonged animal survival. Markers of apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining, cytochrome C release, and caspase 3 activity) were consistently decreased, and animal survival was prolonged after blocking TNF alpha. In contrast, inhibition of Fas signaling did not alter parameters of tissue injury or apoptosis, and animal survival remained unchanged. CONCLUSIONS: We identify TNF-alpha as a crucial inducer of apoptotic cell death in the ischemic liver. A role for Fas could not be identified. These findings may lead to novel strategies to prevent ischemic injury of the liver. PMID- 11781295 TI - Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. AB - BACKGROUND & AIMS: Germline mutations in the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 are associated with susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). Because a significant proportion of hMLH1 mutations are missense, the assessment of their pathogenic role may be difficult. To date, functional analysis of missense mutations has been performed primarily in Saccharomyces cerevisiae. The aim of this study was to examine the biochemical properties of hMLH1 protein variants in a human expression system. METHODS: The HNPCC-related hMLH1 mutations T117M, V185G, R217C, G244D, R265C, V326A, and K618T, the polymorphisms I219V and R265H, and a hMLH1 splicing variant lacking exon 9 and 10 (hMLH1 Delta 9/10) were cloned. On transfection of these constructs into human 293T cells, which do not express hMLH1 because of promoter hypermethylation, the hMLH1 protein variants were analyzed by Western blotting and in a MMR assay. RESULTS: Transfection was successful for all hMLH1 constructs. As anticipated, the mutations K618T and T117M, which affect the highly conserved domains of hMLH1 that are necessary for interaction with hPMS2 or for adenosine triphosphate (ATP) binding, respectively, affected protein stability or its ability to complement MMR-deficient 293T-cell extracts. The V185G, G244D, and Delta 9/10 variants were also unable to complement MMR in 293T cells, whereas hMLH1 proteins carrying the I219V, R265H, R265C, R217C, and V326A mutations were MMR competent. CONCLUSIONS: These data show that the pathogenic role of hMLH1 missense mutations and splicing variants can be assessed by analyzing the biochemical properties of their protein products in a homologous expression system. PMID- 11781296 TI - Esophageal stenosis in childhood: dystrophic epidermolysis bullosa without skin blistering due to collagen VII mutations. AB - We report a 9-year-old girl who experienced recurrent dysphagia since infancy. Crohn's disease was suspected because she had aphthous ulcers of the mouth and anal dermatitis with hematochezia. After bougienages of esophageal stenoses and medication for inflammatory bowel disease proved unsuccessful, interdisciplinary re-examination revealed the cause of the symptoms to be an extracutaneous form of dystrophic epidermolysis bullosa, a genetic skin fragility disorder. Dystrophic epidermolysis bullosa is caused by mutations in the COL7A1 gene encoding collagen VII, a protein of the epidermal attachment complex, and typically manifests with trauma-induced skin blistering, scarring, nail dystrophy, and, in some cases, mucosal involvement. The present proband never developed skin blisters but had nail dystrophy and erosions of the oral, esophageal, and genitoanal mucosa, which healed with slight scarring. Mutation analysis disclosed compound heterozygosity for recessive mutations in the COL7A1 gene. The paternal mutation 425 A-->G caused abnormal splicing resulting in a premature stop codon. The maternal mutation G2775S led to the substitution of a glycine by a serine in the triple helical domain of collagen VII. This case shows that mucosal disease and esophageal strictures in childhood are not always acquired, but can also represent a genetic defect of dermal-epidermal adhesion, even in the absence of skin blistering. PMID- 11781297 TI - The impact of surgery for ulcerative colitis on fertility and sexual function in women. PMID- 11781298 TI - Unsettling facts of life: bacterial commensalism, epithelial adherence, and inflammatory bowel disease. PMID- 11781299 TI - The cost-effectiveness of aspirin for chemoprevention of colorectal cancer. PMID- 11781300 TI - Chemoprevention of intestinal polyposis by COX-2 inhibition: from mouse to man. PMID- 11781301 TI - Are two tests better than one? PMID- 11781302 TI - Interferon treatment of HCV: do we need a virological response? PMID- 11781303 TI - Elimination of Helicobacter pylori or acid in high-risk users of aspirin or nonsteroidal medications: final answer? PMID- 11781305 TI - Antiviral activity of interferon-alpha against hepatitis B virus can be studied in non-hepatic cells and Is independent of MxA. AB - It is well established that interferon-alpha can induce non-cytotoxic intracellular suppression of hepatitis B virus replication, but the mechanisms involved are unclear. Cell culture studies to characterize these mechanisms are restricted, in part because hepatitis B virus replicates almost exclusively in liver-derived cells. To overcome this limitation we used a cytomegalovirus promoter-controlled hepatitis B virus expression system, which leads to intracellular viral replication even in non-hepatic cell lines. In this experimental system interferon-alpha treatment specifically suppressed viral replication demonstrating that antiviral activities against hepatitis B virus are not restricted to hepatic cells. Furthermore, the interferon-inducible MxA protein was recently reported to play a key role in the antiviral action of interferon-alpha against hepatitis B virus. Our data demonstrate that interferon alpha also suppresses hepatitis B virus replication in MxA-deficient HEp2 cells, indicating that MxA is not essential for these activities. Taken together, our data imply that the experimental approach presented can also be adapted to established cell lines which are deficient in parts of the signal transduction pathway or other elements located further downstream, providing important insights into mechanisms specifically suppressing hepatitis B virus. PMID- 11781306 TI - Phosphatidylinositol (3,4,5)P3 is essential but not sufficient for protein kinase B (PKB) activation; phosphatidylinositol (3,4)P2 is required for PKB phosphorylation at Ser-473: studies using cells from SH2-containing inositol-5 phosphatase knockout mice. AB - Using bone marrow derived mast cells from SH2-containing inositol-5-phosphatase (SHIP) +/+ and minus sign/minus sign mice, we found that the loss of SHIP leads to a dramatic increase in Steel Factor (SF)-stimulated phosphatidylinositol 3,4,5 trisphosphate (PI(3,4,5)P(3)), a substantial reduction in PI(3,4)P(2), and no change in PI(4,5)P(2) levels. We also found that SF-induced activation of protein kinase B (PKB) is increased and prolonged in SHIP -/- cells, due in large part to more PKB associating with the plasma membrane in these cells. Pretreatment of SHIP -/- cells with 25 microm LY294002 resulted in complete inhibition of SF induced PI(3,4)P(2), while still yielding PI(3,4,5)P(3) levels similar to those achieved in SHIP+/+ cells. This offered a unique opportunity to study the regulation of PKB by PI(3,4,5)P(3), in the absence of PI(3,4)P(2). Under these conditions, PKB activity was markedly reduced compared with that in SF-stimulated SHIP+/+ cells, even though more PKB localized to the plasma membrane. Although phosphoinositide-dependent kinase 1 mediated phosphorylation of PKB at Thr-308 was unaffected by LY294002, phosphorylation at Ser-473 was dramatically reduced. Moreover, intracellular delivery of PI(3,4)P(2) to LY294002-pretreated, SF stimulated SHIP -/- cells increased phosphorylation of PKB at Ser-473 and increased PKB activity. These results are consistent with a model in which SHIP serves as a regulator of both activity and subcellular localization of PKB. PMID- 11781307 TI - Contribution of estrogen receptor alpha to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway. AB - We previously reported that enhanced transcriptional activation of estrogen receptor alpha (ERalpha) contributed to [(12)Val]K-Ras-mediated NIH3T3 cell transformation. Functional inactivation of ERalpha by a dominant negative mutant of ERalpha (DNER) in the presence of activated K-Ras 4B mutant arrested the cell cycle at G(0)/G(1), subsequently provoking replicative cell senescence, finally abrogating tumorigenic potential. p53-dependent up-regulation of p21 was implicated in this cell senescence induction. Alterations in the MDM2 protein in response to DNER accounted for this p21-mediated cell senescence induction. An oncogenic K-Ras 4B mutant significantly increased MDM2 proteins coprecipitated with p53, and suppressed p53 transcriptional activity. In turn, DNER exerted its function to decrease MDM2 proteins coprecipitated with p53, followed by the stimulation of p53 activity in the presence of the oncogenic K-Ras 4B mutant. In addition, overexpression of wild type ERalpha in NIH3T3 cells resulted in the significant increase in the MDM2 protein level and the resultant suppression of p53 transcriptional activity. Finally, we demonstrated that c-Jun expression overcame the suppression and resultant enhancement of p21 protein level in response to DNER. The data imply that the ERalpha-AP1 pathway activated by oncogenic K-Ras 4B mutant contributes to the NIH3T3 cells' transformation by modulating p53 transcriptional activity through MDM2. PMID- 11781308 TI - Activation mechanism of Gi and Go by reactive oxygen species. AB - Reactive oxygen species are proposed to work as intracellular mediators. One of their target proteins is the alpha subunit of heterotrimeric GTP-binding proteins (Galpha(i) and Galpha(o)), leading to activation. H(2)O(2) is one of the reactive oxygen species and activates purified Galpha(i2). However, the activation requires the presence of Fe(2+), suggesting that H(2)O(2) is converted to more reactive species such as c*OH. The analysis with mass spectrometry shows that seven cysteine residues (Cys(66), Cys(112), Cys(140), Cys(255), Cys(287), Cys(326), and Cys(352)) of Galpha(i2) are modified by the treatment with *OH. Among these cysteine residues, Cys(66), Cys(112), Cys(140), Cys(255), and Cys(352) are not involved in *OH-induced activation of Galpha(i2). Although the modification of Cys(287) but not Cys(326) is required for subunit dissociation, the modification of both Cys(287) and Cys(326) is necessary for the activation of Galpha(i2) as determined by pertussis toxin-catalyzed ADP-ribosylation, conformation-dependent change of trypsin digestion pattern or guanosine 5'-3-O (thio)triphosphate binding. Wild type Galpha(i2) but not Cys(287)- or Cys(326) substituted mutants are activated by UV light, singlet oxygen, superoxide anion, and nitric oxide, indicating that these oxidative stresses activate Galpha(i2) by the mechanism similar to *OH-induced activation. Because Cys(287) exists only in G(i) family, this study explains the selective activation of G(i)/G(o) by oxidative stresses. PMID- 11781309 TI - Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. AB - It was recently demonstrated that mutations in the human SPTLC1 gene, encoding the Lcb1p subunit of serine palmitoyltransferase (SPT), cause hereditary sensory neuropathy type I . As a member of the subfamily of pyridoxal 5'-phosphate enzymes known as the alpha-oxoamine synthases, serine palmitoyltransferase catalyzes the committed step of sphingolipid synthesis. The residues that are mutated to cause hereditary sensory neuropathy type I reside in a highly conserved region of Lcb1p that is predicted to be a catalytic domain of Lcb1p on the basis of alignments with other members of the alpha-oxoamine synthase family. We found that the corresponding mutations in the LCB1 gene of Saccharomyces cerevisiae reduce serine palmitoyltransferase activity. These mutations are dominant and decrease serine palmitoyltransferase activity by 50% when the wild type and mutant LCB1 alleles are coexpressed. We also show that serine palmitoyltransferase is an Lcb1p small middle dotLcb2p heterodimer and that the mutated Lcb1p proteins retain their ability to interact with Lcb2p. Modeling studies suggest that serine palmitoyltransferase is likely to have a single active site that lies at the Lcb1p small middle dotLcb2p interface and that the mutations in Lcb1p reside near the lysine in Lcb2p that is expected to form the Schiff's base with the pyridoxal 5'-phosphate cofactor. Furthermore, mutations in this lysine and in a histidine residue that is also predicted to be important for pyridoxal 5'-phosphate binding to Lcb2p also dominantly inactivate SPT similar to the hereditary sensory neuropathy type 1-like mutations in Lcb1p. PMID- 11781310 TI - Inhibition of transforming growth factor beta signaling and Smad-dependent activation of transcription by the Latent Membrane Protein 1 of Epstein-Barr virus. AB - Inhibition of transforming growth factor beta (TGFbeta) signaling by the Epstein Barr virus Latent Membrane Protein 1 (LMP1) may account, at least in part, for the oncogenic activity of LMP1. We found that LMP1 is a potent inhibitor of TGFbeta signaling and Smad-dependent activation of transcription in 293 epithelial cells and COS-7 fibroblasts. LMP1 strongly inhibited the uninduced and the Smad-inducible activity of the promoters of the human p21/WAF1/Cip1 gene and the mouse Smad7 gene. Inhibition of TGFbeta signaling and Smad-dependent activation of transcription by LMP1 was greatly reduced by deletion of both C terminal activating regions 1 and 2 of LMP1 as well as by overexpression of a non degradable form of IkappaB. In contrast, specific inhibitors of p38 kinase or MEK kinase did not reverse the inhibitory activity of LMP1. TGFbeta signaling was enhanced by overexpression of dominant negative forms of the LMP1 effectors TRAF2, NIK, and IKKbeta and was abolished by overexpression of p65/RelA or a p50/p65 fusion protein. Deletion of the transactivation domain of p65 abolished its inhibitory activity. Immunoblotting and immunofluorescence microscopy indicated that suppression of TGFbeta signaling and Smad transcriptional activity by LMP1 was not due to Smad degradation or cytoplasmic retention suggesting that LMP1 affects the nuclear function of Smad proteins. Our data are consistent with an essential role of NF-kappaB activation by LMP1 in the inhibition of TGFbeta signaling and Smad-mediated transcriptional responses. PMID- 11781311 TI - Essential cytoplasmic domains in the Escherichia coli TatC protein. AB - The twin-arginine translocation (Tat) system mediates the transport of proteins across the bacterial plasma membrane and chloroplast thylakoid membrane. Operating in parallel with Sec-type systems in these membranes, the Tat system is completely different in both structural and mechanistic terms, and is uniquely able to catalyze the translocation of fully folded proteins across coupled membranes. TatC is an essential, multispanning component that has been proposed to form part of the binding site for substrate precursor proteins. In this study we have tested the importance of conserved residues on the periplasmic and cytoplasmic face of the Escherichia coli protein. We find that many of the mutations on the cytoplasmic face have little or no effect. However, substitution at several positions in the extreme N-terminal cytoplasmic region or the predicted first cytoplasmic loop lead to a significant or complete loss of Tat dependent export. The mutated strains are unable to grow anaerobically on trimethylamine N-oxide minimal media and are unable to export trimethylamine-N oxide reductase (TorA). The same mutants are completely unable to export a chimeric protein, comprising the TorA signal peptide linked to green fluorescent protein, indicating that translocation is blocked rather than cofactor insertion into the TorA mature protein. The data point to two essential cytoplasmic domains on the TatC protein that are essential for export. PMID- 11781312 TI - Association of GM3 with Zap-70 induced by T cell activation in plasma membrane microdomains: GM3 as a marker of microdomains in human lymphocytes. AB - Recent evidence demonstrated that T cell activation leads to the redistribution of membrane and intracellular kinase-rich raft microdomains at the site of TCR engagement. In this investigation we demonstrated by high performance thin layer chromatography, gas chromatographic, and mass spectrometric analyses that GM3 is the main ganglioside constituent of these microdomains in human lymphocytes. Then we analyzed GM3 distribution and its interaction with the phosphorylation protein Zap-70. Human T lymphocytes were stimulated with anti-CD3 and anti-CD28. Immunofluorescence microscopy analysis revealed a clustered GM3 distribution over the cell surface and an intracellular localization resembling specific cytoplasmic compartment(s). Scanning confocal microscopy showed that T cell activation induced a significant association between GM3 and Zap-70, as revealed by nearly complete colocalization areas; very few colocalization areas were detected in unstimulated cells. Coimmunoprecipitation experiments revealed that GM3 was immunoprecipitated by anti-Zap-70 only after co-stimulation through CD3 and CD28 as detected by both thin layer chromatography and immunoblotting. Therefore, T cell activation does not promote a redistribution of glycosphingolipid-enriched microdomains but induces Zap-70 translocation in selective membrane domains in which Zap-70 may interact with GM3. These findings suggest that GM3 is a component of a multimolecular signaling complex involved in T cell activation. PMID- 11781313 TI - Characterization of the nuclear export signal of polypyrimidine tract-binding protein. AB - The polypyrimidine tract-binding protein (PTB) is a nuclear protein that regulates alternative splicing. In addition, it plays a role in the cytoplasm during infection by some viruses and functions as a positive effector of hepatitis B virus RNA export. Thus, it presumably contains a nuclear export signal (NES). Using a heterokaryon export assay in transfected cultured cells, we have shown that the N-terminal 25 amino acid residues of PTB function as an autonomous NES, with residues 11-16 being important for its activity. Unlike the heteronuclear ribonucleoprotein A1 NES, this NES is separable from the nuclear localization signal, which spans the entire N-terminal 60 residues of PTB. The PTB NES cannot be shown to bind to CAS or Crm1, cellular receptors known to export proteins from the nucleus, and it functions in the presence of leptomycin B, a specific inhibitor of Crm1-dependent export. PTB deleted of its NES, unlike wild type PTB, does not stimulate the export of hepatitis B virus RNA. Therefore, the PTB NES is a functionally important domain of this multifunctional protein that utilizes an unknown export receptor. PMID- 11781314 TI - Liver X receptors as insulin-mediating factors in fatty acid and cholesterol biosynthesis. AB - The nuclear receptor liver X receptor (LXR) alpha, an important regulator of cholesterol and bile acid metabolism, was analyzed after insulin stimulation in liver in vitro and in vivo. A time- and dose-dependent increase in LXRalpha steady-state mRNA level was seen after insulin stimulation of primary rat hepatocytes in culture. A maximal induction of 10-fold was obtained when hepatocytes were exposed to 400 nm insulin for 24 h. Cycloheximide, a potent inhibitor of protein synthesis, prevented induction of LXRalpha mRNA expression by insulin, indicating that the induction is dependent on de novo synthesis of proteins. Stabilization studies using actinomycin D indicated that insulin stimulation increased the half-life of LXRalpha transcripts in cultured primary hepatocytes. Complementary studies where rats and mice were injected with insulin induced LXRalpha mRNA levels and confirmed our in vitro studies. Furthermore, deletion of both the LXRalpha and LXRbeta genes (double knockout) in mice markedly suppressed insulin-mediated induction of an entire class of enzymes involved in both fatty acid and cholesterol metabolism. The discovery of insulin regulation of LXR in hepatic tissue as well as gene targeting studies in mice provide strong evidence that LXRs plays a central role not only in cholesterol homeostasis, but also in fatty acid metabolism. Furthermore, LXRs appear to be important insulin-mediating factors in regulation of lipogenesis. PMID- 11781315 TI - Cooperation of STAT-1 and IRF-1 in interferon-gamma-induced transcription of the gp91(phox) gene. AB - Interferon (IFN)-gamma induces the expression of the gp91(phox) gene both during myeloid differentiation and also in mature phagocytes through several cis elements and their binding proteins. To find new cis-elements for this induction, transient expression assays were performed using a reporter gene driven by serially truncated gp91(phox) promoters in U937 cells. The results suggest that a critical cis-element for induction exists in the region from bp -115 to -96 of the promoter. Site-directed mutagenesis showed that a gamma-activated sequence (GAS) element at bp -100 (-100GAS) of the gp91(phox) promoter plays a pivotal role for the IFN-gamma-dependent activity of the bp -115 to +12 region of the gp91(phox) promoter. Electrophoretic mobility shift assays using several GAS competitors and specific antibodies indicated that phosphorylated STAT-1alpha specifically binds to the -100GAS. Site-directed mutagenesis showed that an interferon-stimulated response element (ISRE) at bp -88 (-88ISRE) mediates the induction of the gene by IFN-gamma in cooperation with -100GAS. Electrophoretic mobility shift assay showed that IRF-1 dominantly binds to -88ISRE in an IFN gamma-dependent fashion. These results demonstrate a new mechanism for IFN-gamma induced transcription of the gp91(phox) gene by the cooperation of STAT-1alpha and IRF-1 binding to -100GAS and -88ISRE, respectively. PMID- 11781316 TI - Small molecule inhibitors induce conformational changes in the I domain and the I like domain of lymphocyte function-associated antigen-1. Molecular insights into integrin inhibition. AB - The beta(2) integrin lymphocyte function-associated antigen-1 (LFA-1) is a conformationally flexible alpha/beta heterodimeric receptor, which is expressed on the surface of all leukocytes. LFA-1 mediates cell adhesion crucial for normal immune and inflammatory responses. Intracellular signals or cations are required to convert LFA-1 from a nonligand binding to a ligand binding state. Here we investigated the effect of small molecule inhibitors on LFA-1 by monitoring the binding of monoclonal antibodies mapped to different receptor domains. The inhibitors were found to not only induce epitope changes in the I domain of the alpha(L) chain but also in the I-like domain of the beta(2) chain depending on the individual chemical structure of the inhibitor and its binding site. For the first time, we provide strong evidence that the I-like domain represents a target for allosteric LFA-1 inhibition similar to the well established regulatory L-site on the I domain of LFA-1. Moreover, the antibody binding patterns observed in the presence of the various inhibitors establish a conformational interaction between the LFA-1 I domain and the I-like domain in the native receptor that is formed upon activation. Differentially targeting the binding sites of the inhibitors, the L-site and the I-like domain, may open new avenues for highly specific therapeutic intervention in diseases where integrins play a pathophysiological role. PMID- 11781317 TI - Syncytium formation and HIV-1 replication are both accentuated by purified influenza and virus-associated neuraminidase. AB - The degree of sialylation has been shown previously to modulate the process of human immunodeficiency virus type-1 (HIV-1) infection by affecting the interaction between the virus and CD4-expressing target cells. In the present study, we investigated whether HIV-1 replication cycle was affected by neuraminidase (NA) derived from the human influenza (flu) virus. We first demonstrate that the level of HIV-1-mediated syncytium formation was greatly enhanced in the presence of purified flu NA. Pretreatment of established monocytic and lymphocytic cell lines as well as primary mononuclear cells with purified flu NA augmented also the process of virus infection. A comparable up regulating effect was observed when using several strains of UV-inactivated whole flu virus, thereby suggesting that virus-anchored NA enzymes positively modulate the HIV-1 life cycle. Furthermore, flu NA-mediated positive effect on HIV-1 biology was abrogated with zanamivir, a specific flu NA inhibitor. Our results provide a new model allowing the investigation of the potential benefit of using NA inhibitors in the treatment of HIV-1-infected patients suffering from coinfection with NA-bearing pathogens. PMID- 11781319 TI - The ankyrin-B C-terminal domain determines activity of ankyrin-B/G chimeras in rescue of abnormal inositol 1,4,5-trisphosphate and ryanodine receptor distribution in ankyrin-B (-/-) neonatal cardiomyocytes. AB - Ankyrins are a closely related family of membrane adaptor proteins that are believed to participate in targeting diverse membrane proteins to specialized domains in the plasma membrane and endoplasmic reticulum. This study addresses the question of how individual ankyrin isoforms achieve functional specificity when co-expressed in the same cell. Cardiomyocytes from ankyrin-B (-/-) mice display mis-localization of inositol 1,4,5-trisphosphate receptors and ryanodine receptors along with reduced contraction rates that can be rescued by expression of green fluorescent protein (GFP)-ankyrin-B but not GFP-ankyrin-G. We developed chimeric GFP expression constructs containing all combinations of the three major domains of ankyrin-B and ankyrin-G to determine which domain(s) of ankyrin-B are required for ankyrin-B-specific functions. The death/C-terminal domain of ankyrin B determined activity of ankyrin-B/G chimeras in localization in a striated pattern in cardiomyocytes and in restoration of a normal striated distribution of both ryanodine and inositol 1,4,5-trisphosphate receptors as well as normal beat frequency of contracting cardiomyocytes. Further deletions within the death/C terminal domain demonstrated that the C-terminal domain determines ankyrin-B activity, whereas deletion of the death domain had no effect. C-terminal domains are the most divergent between ankyrin isoforms and are candidates to encode the signal(s) that enable ankyrins to selectively target proteins to diverse cellular sites. PMID- 11781318 TI - Translation mediated by the internal ribosome entry site of the cat-1 mRNA is regulated by glucose availability in a PERK kinase-dependent manner. AB - The cationic amino acid transporter, Cat-1, is a high affinity transporter of the essential amino acids, arginine and lysine. Expression of the cat-1 gene is known to be regulated by amino acid availability. It is shown here that cat-1 gene expression is also induced by Glc limitation, which causes a 7-fold increase in cat-1 mRNA, a 30-fold induction of Cat-1 protein levels, and a 4-fold stimulation of arginine uptake. Glc limitation is known to induce the unfolded protein response (UPR) by altering protein glycosylation in the endoplasmic reticulum (ER). The studies here demonstrate that synthesis of Cat-1 occurs during the UPR when global protein synthesis is inhibited. The 5'-UTR of the cat-1 mRNA contains an internal ribosomal entry site (IRES) that is activated by amino acid starvation by a mechanism that involves phosphorylation of the translation initiation factor, eukaryotic initiation factor 2alpha, by the GCN2 kinase. It is shown here that translation from the cat-1/IRES is also induced by Glc deprivation in a manner dependent upon phosphorylation of eukaryotic initiation factor 2alpha by the transmembrane ER kinase, PERK. Because PERK is a key constituent of the UPR, it is concluded that induction of cat-1 gene expression is part of the adaptive response of cells to ER stress. These results also demonstrate that regulation of IRES activity in cellular mRNAs is part of the mechanism by which the UPR protects cells from unfolded proteins in the ER. PMID- 11781320 TI - Differential determinants for peptide and non-peptidyl ligand binding to the motilin receptor. Critical role of second extracellular loop for peptide binding and action. AB - The predicted second extracellular loop domain of the motilin receptor is of particular interest because it is a region that is quite distinct from the analogous regions in other family members that are most closely related and because the initial report of the photoaffinity labeling of a domain of this receptor included this region (Coulie, B. J., Matsuura, B., Dong, M., Hadac, E. M., Pinon, D. I., Feighner, S. D., Howard, A. D., and Miller, L. J. (2001) J. Biol. Chem. 276, 35518-35522). In the current work, motilin receptor constructs were prepared that included sequential deletions ranging from single residues to twelve amino acid segments throughout this 67 amino acid domain. Each construct was expressed in COS cells and characterized for motilin radioligand binding and motilin-stimulated intracellular calcium responses. The only segments that had negative impact on motilin binding and biological activity included deletion constructs DeltaCys(235), Delta179-182, and Delta241-246. Cys(235) is likely involved in the highly conserved and functionally important disulfide bond linking the first and second loops of G protein-coupled receptors. Alanine replacements for each of the amino acid residues in the other two segments revealed that the perimembranous residues at both ends of this loop, Val(179) and Leu(245) and Arg(246), were responsible for the negative impact on motilin binding and biological activity. Of note, these mutants responded normally to the non-peptidyl agonist, erythromycin. These data support important functional roles for both amino-terminal and carboxyl-terminal perimembranous regions of the second loop for responses to the natural agonist peptide, while supporting independent determinants for action of a non-peptidyl agonist ligand. PMID- 11781321 TI - Conserved residues in domain Ia are required for the reaction of Escherichia coli DNA ligase with NAD+. AB - NAD(+)-dependent DNA ligases are present in all bacteria and are essential for growth. Their unique substrate specificity compared with ATP-dependent human DNA ligases recommends the NAD(+) ligases as targets for the development of new broad spectrum antibiotics. A plausible strategy for drug discovery is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these components and thereby block the binding of NAD(+) to the ligase. The limitation to this strategy is that the structural determinants of NAD(+) specificity are not known. Here we show that reactivity of Escherichia coli DNA ligase (LigA) with NAD(+) requires N-terminal domain Ia, which is unique to, and conserved among, NAD(+) ligases but absent from ATP-dependent ligases. Deletion of domain Ia abolished the sealing of 3' OH/5'-PO(4) nicks and the reaction with NAD(+) to form ligase-adenylate but had no effect on phosphodiester formation at a preadenylated nick. Alanine substitutions at conserved residues within domain Ia either reduced (His-23, Tyr 35) or abolished (Tyr-22, Asp-32, Asp-36) sealing of a 5'-PO(4) nick and adenylyl transfer from NAD(+) without affecting ligation of pre-formed DNA-adenylate. We suggest that these five side chains comprise a binding site for the nicotinamide mononucleotide moiety of NAD(+). Structure-activity relationships were clarified by conservative substitutions. PMID- 11781322 TI - Identification of annexin II heterotetramer as a plasmin reductase. AB - Annexin II heterotetramer (AIIt) is a Ca(2+)- and phospholipid-binding protein that consists of two copies of a p36 and p11 subunit. AIIt regulates the production and autoproteolysis of plasmin at the cell surface. In addition to its role as a key cellular protease, plasmin also plays a role in angiogenesis as the precursor for antiangiogenic proteins. Recently we demonstrated that the primary antiangiogenic plasmin fragment, called A(61) (Lys(78)-Lys(468)) was released from cultured cells. In the present study we report for the first time that AIIt possesses an intrinsic plasmin reductase activity. AIIt stimulated the reduction of the plasmin Cys(462)-Cys(541) bond in a time- and concentration-dependent manner, which resulted in the release of A(61) from plasmin. Mutagenesis of p36 C334S and either p11 C61S or p11 C82S inactivated the plasmin reductase activity of the isolated subunits, suggesting that specific cysteinyl residues participated in the plasmin reductase activity of each subunit. Furthermore, we demonstrated that the loss of AIIt from the cell surface of HT1080 cells transduced with a retroviral vector encoding p11 antisense dramatically reduced the cellular production of A(61) from plasminogen. This is the first demonstration that AIIt regulates the cellular production of the antiangiogenic plasminogen fragment, A(61). PMID- 11781323 TI - Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. AB - Complete lack of transcription factor PDX-1 leads to pancreatic agenesis, whereas heterozygosity for PDX-1 mutations has been recently noted in some individuals with maturity-onset diabetes of the young (MODY) and in some individuals with type 2 diabetes. To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. NAD(P)H generation in response to glucose was reduced by 30% in PDX-1(+/-) mice. The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. The K(m) for insulin release was similar in wild type and PDX 1(+/-) mice. Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. However, insulin secretory responses to 10 mm 2-ketoisocaproate and 20 mm KCl were significantly reduced (by 61 and 66%, respectively). These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. PMID- 11781324 TI - The intermediate filament protein keratin 8 is a novel cytoplasmic substrate for c-Jun N-terminal kinase. AB - Keratins 8 (K8) and 18 are the primary intermediate filaments of simple epithelia. Phosphorylation of keratins at specific sites affects their organization, assembly dynamics, and their interaction with signaling molecules. A number of keratin in vitro and in vivo phosphorylation sites have been identified. One example is K8 Ser-73, which has been implicated as an important phosphorylation site during mitosis, cell stress, and apoptosis. We show that K8 is strongly phosphorylated on Ser-73 upon stimulation of the pro-apoptotic cytokine receptor Fas/CD95/Apo-1 in HT-29 cells. Kinase assays showed that c-Jun N-terminal kinase (JNK) was also activated with activation kinetics corresponding to that of K8 phosphorylation. Furthermore, K8 was also phosphorylated on Ser-73 by JNK in vitro, yielding similar phosphopeptide maps as the in vivo phosphorylated material. In addition, co-immunoprecipitation studies revealed that part of JNK is associated with K8 in vivo, correlating with decreased ability of JNK to phosphorylate the endogenous c-Jun. Taken together, K8 is a new cytoplasmic target for JNK in Fas receptor-mediated signaling. The functional significance of this phosphorylation could relate to regulation of JNK signaling and/or regulation of keratin dynamics. PMID- 11781325 TI - Acute agonist-mediated desensitization of the human alpha 1a-adrenergic receptor is primarily independent of carboxyl terminus regulation: implications for regulation of alpha 1aAR splice variants. AB - Despite important roles in myocardial hypertrophy and benign prostatic hyperplasia, little is known about acute effects of agonist stimulation on alpha(1a)-adrenergic receptor (alpha(1a)AR) signaling and function. Regulatory mechanisms are likely complex since 12 distinct human alpha(1a)AR carboxyl terminal splice variants have been isolated. After determining the predominance of the alpha(1a-1)AR isoform in human heart and prostate, we stably expressed an epitope-tagged alpha(1a-1)AR cDNA in rat-1 fibroblasts and subsequently examined regulation of signaling, phosphorylation, and internalization of the receptor. Human alpha(1a)AR-mediated inositol phosphate signaling is acutely desensitized in response to both agonist and phorbol 12-myristate 13-acetate (PMA) exposure. Concurrent with desensitization, alpha(1a)ARs in (32)P(i)-labeled cells are rapidly phosphorylated in response to both NE and PMA stimulation. Despite the ability of PKC to desensitize alpha(1a)ARs when directly activated with PMA, inhibitors of PKC have no effect on agonist-mediated desensitization. In contrast, involvement of GRK kinases is suggested by the ability of GRK2 to desensitize alpha(1a)ARs. Internalization of cell surface alpha(1a)ARs also occurs in response to agonist stimulation (but not PKC activation), but is initiated more slowly than receptor desensitization. Significantly, deletion of the alpha(1a)AR carboxyl terminus has no effect on receptor internalization or either agonist-induced or GRK-mediated receptor desensitization. Because mechanisms underlying acute agonist-mediated regulation of human alpha(1a)ARs are primarily independent of the carboxyl terminus, they may be common to all functional alpha(1a)AR isoforms. PMID- 11781326 TI - Determinants of L-aspartate and IMP recognition in Escherichia coli adenylosuccinate synthetase. AB - Adenylosuccinate synthetase governs the first committed step in the de novo synthesis of AMP. Mutations of conserved residues in the synthetase from Escherichia coli reveal significant roles for Val(273) and Thr(300) in the recognition of l-aspartate, even though these residues do not or cannot hydrogen bond with the substrate. The mutation of Thr(300) to alanine increases the K(m) for l-aspartate by 30-fold. In contrast, its mutation to valine causes no more than a 4-fold increase in the K(m) for l-aspartate, while increasing k(cat) by 3 fold. Mutations of Val(273) to alanine, threonine, or asparagine increase the K(m) for l-aspartate from 15- to 40-fold, and concomitantly decrease the K(i) for dicarboxylate analogues of l-aspartate by up to 40-fold. The above perturbations are comparable with those resulting from the elimination of a hydrogen bond between the enzyme and substrate: alanine mutations of Thr(128) and Thr(129) increase the K(m) for IMP by up to 30-fold and the alanine mutation of Thr(301) abolishes catalysis supported by l-aspartate, but has no effect on catalysis supported by hydroxylamine. Structure-based mechanisms, by which the above residues influence substrate recognition, are presented. PMID- 11781327 TI - Functional characterization of Delta3,Delta2-enoyl-CoA isomerases from rat liver. AB - The degradation of unsaturated fatty acids by beta-oxidation involves Delta(3),Delta(2)-enoyl-CoA isomerases (enoyl-CoA isomerases) that catalyze 3-cis --> 2-trans and 3-trans --> 2-trans isomerizations of enoyl-CoAs and the 2,5 --> 3,5 isomerization of dienoyl-CoAs. An analysis of rat liver enoyl-CoA isomerases revealed the presence of a monofunctional enoyl-CoA isomerase (ECI) in addition to mitochondrial enoyl-CoA isomerase (MECI) in mitochondria, whereas peroxisomes contain ECI and multifunctional enzyme 1 (MFE1). Thus ECI, which previously had been described as peroxisomal enoyl-CoA isomerase, was found to be present in both peroxisomes and mitochondria. This enzyme seems to be identical with mitochondrial long-chain enoyl-CoA isomerase (Kilponen, J.M., Palosaari, P.M., and Hiltunen, J.K. 1990. Biochem. J. 269, 223-226). All three hepatic enoyl-CoA isomerases have broad chain length specificities but are distinguishable by their preferences for one of the three isomerization reactions. MECI is most active in catalyzing the 3-cis --> 2-trans isomerization; ECI has a preference for the 3 trans --> 2-trans isomerization, and MFE1 is the optimal isomerase for the 2,5 - > 3,5 isomerization. A functional characterization based on substrate specificities and total enoyl-CoA isomerase activities in rat liver leads to the conclusion that the 3-cis --> 2-trans and 2,5 --> 3,5 isomerizations in mitochondria are catalyzed overwhelmingly by MECI, whereas ECI contributes significantly to the 3-trans --> 2-trans isomerization. In peroxisomes, ECI is predicted to be the dominant enzyme for the 3-cis --> 2-trans and 3-trans --> 2 trans isomerizations of long-chain intermediates, whereas MFE1 is the key enzyme in the 2,5 --> 3,5 isomerization. PMID- 11781328 TI - Stoichiometry and structural effect of the cyclic nucleotide binding to cyclic AMP receptor protein. AB - Cyclic AMP receptor protein (CRP) is a homodimeric protein, which is activated by cAMP binding to function as a transcriptional regulator of many genes in prokaryotes. Until now, the actual number of cAMP molecules that can be bound by CRP in solution has been ambiguous. In this work, we performed a nuclear magnetic resonance study on CRP to investigate the stoichiometry of cyclic nucleotide binding to CRP. A series of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the protein in the absence and in the presence of cAMP or cGMP were analyzed. The addition of cAMP to CRP induced a biphasic spectral change up to 4 equivalents, whereas the cGMP addition made a monophasic change up to 2 equivalents. Altogether, the results not only established for the first time that CRP possesses two cyclic AMP-binding sites in each monomer, even in a solution without DNA, but also suggest that the syn-cAMP binding sites of the CRP dimer can be formed by an allosteric conformational change of the protein upon the binding of two anti-cAMPs at the N-terminal domain. In addition, a residue specific inspection of the spectral changes provides some new structural information about the cAMP-induced allosteric activation of CRP. PMID- 11781329 TI - Phospholipid-cytochrome c interaction: evidence for the extended lipid anchorage. AB - Binding of cytochrome c (cyt c) to fatty acids and acidic phospholipid membranes produces pronounced and essentially identical changes in the spectral properties of cyt c, revealing conformational changes in the protein. The exact mechanism of the interaction of fatty acids and acidic phospholipids with cyt c is unknown. Binding of cyt c to liposomes with high contents (mole fraction X > 0.7) of acidic phospholipids caused spectral changes identical to those due to binding of oleic acid. Fluorescence spectroscopy of a cyt c analog containing a Zn(2+) substituted heme moiety and brominated lipid derivatives (9,10)-dibromostearate and 1-palmitoyl-2-(9,10)-dibromo-sn-glycero-3-phospho-rac-glycerol demonstrated a direct contact between the fluorescent [Zn(2+)-heme] group and the brominated acyl chain. These data constitute direct evidence for interaction between an acyl chain of a membrane phospholipid and the inside of the protein containing the heme moiety and provide direct evidence for the so-called extended-lipid anchorage of cyt c to phospholipid membranes. In this mechanism, one of the phospholipid acyl chains protrudes out of the membrane and intercalates into a hydrophobic channel in cyt c while the other chain remains in the bilayer. PMID- 11781330 TI - Myelination: some receptors required. AB - Feltri et al. (2001)(this issue) succeed in disrupting beta 1 integrin specifically in Schwann cells, and in so doing, demonstrate that it is required for normal myelination. Their results reveal that signaling by an extracellular matrix receptor plays a key role in the differentiation of myelinating Schwann cells. PMID- 11781331 TI - Micro-RNAs: small is plentiful. AB - Two small temporally regulated RNAs (stRNAs)* of approximately 22 nucleotides regulate timing of gene expression during development of the nematode C. elegans. This regulation occurs at a posttranscriptional, presumably translational, level and is distinct from RNA interference (RNAi). One of the two stRNAs, let-7, as well as its target gene, lin-41, are highly conserved even in humans, suggesting a wide employment of stRNA-mediated gene regulation. Recent reports indicate that these two stRNAs are indeed likely to represent only the tip of an iceberg with hundreds or more of additional micro-RNAs (miRNAs) existing in metazoans. miRNAs might thus be previously underestimated key participants in the field of gene regulation. PMID- 11781332 TI - Internal Ca(2+) release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. AB - Calcium ions, present inside all eukaryotic cells, are important second messengers in the transduction of biological signals. In mammalian cells, the release of Ca(2+) from intracellular compartments is required for signaling and involves the regulated opening of ryanodine and inositol-1,4,5-trisphosphate (IP3) receptors. However, in budding yeast, no signaling pathway has been shown to involve Ca(2+) release from internal stores, and no homologues of ryanodine or IP3 receptors exist in the genome. Here we show that hyperosmotic shock provokes a transient increase in cytosolic Ca(2+) in vivo. Vacuolar Ca(2+), which is the major intracellular Ca(2+) store in yeast, is required for this response, whereas extracellular Ca(2+) is not. We aimed to identify the channel responsible for this regulated vacuolar Ca(2+) release. Here we report that Yvc1p, a vacuolar membrane protein with homology to transient receptor potential (TRP) channels, mediates the hyperosmolarity induced Ca(2+) release. After this release, low cytosolic Ca(2+) is restored and vacuolar Ca(2+) is replenished through the activity of Vcx1p, a Ca(2+)/H(+) exchanger. These studies reveal a novel mechanism of internal Ca(2+) release and establish a new function for TRP channels. PMID- 11781333 TI - Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length. AB - Myosins are molecular motors that exert force against actin filaments. One widely conserved myosin class, the myosin-Vs, recruits organelles to polarized sites in animal and fungal cells. However, it has been unclear whether myosin-Vs actively transport organelles, and whether the recently challenged lever arm model developed for muscle myosin applies to myosin-Vs. Here we demonstrate in living, intact yeast that secretory vesicles move rapidly toward their site of exocytosis. The maximal speed varies linearly over a wide range of lever arm lengths genetically engineered into the myosin-V heavy chain encoded by the MYO2 gene. Thus, secretory vesicle polarization is achieved through active transport by a myosin-V, and the motor mechanism is consistent with the lever arm model. PMID- 11781334 TI - A predominantly nuclear protein affecting cytoplasmic localization of beta-actin mRNA in fibroblasts and neurons. AB - The localization of beta-actin mRNA to the leading lamellae of chicken fibroblasts and neurite growth cones of developing neurons requires a 54-nt localization signal (the zipcode) within the 3' untranslated region. In this study we have identified and isolated five proteins binding to the zipcode. One of these we previously identified as zipcode binding protein (ZBP)1, a 4-KH domain protein. A second is now investigated in detail: a 92-kD protein, ZBP2, that is especially abundant in extracts from embryonic brain. We show that ZBP2 is a homologue of the human hnRNP protein, KSRP, that appears to mediate pre-mRNA splicing. However, ZBP2 has a 47-amino acid (aa) sequence not present in KSRP. Various portions of ZBP2 fused to GFP indicate that the protein most likely shuttles between the nucleus and the cytoplasm, and that the 47-aa insert promotes the nuclear localization. Expression of a truncated ZBP2 inhibits the localization of beta-actin mRNA in both fibroblast and neurons. These data suggest that ZBP2, although predominantly a nuclear protein, has a role in the cytoplasmic localization of beta-actin mRNA. PMID- 11781335 TI - Induction of maturation-promoting factor during Xenopus oocyte maturation uncouples Ca(2+) store depletion from store-operated Ca(2+) entry. AB - During oocyte maturation, eggs acquire the ability to generate specialized Ca(2+) signals in response to sperm entry. Such Ca(2+) signals are crucial for egg activation and the initiation of embryonic development. We examined the regulation during Xenopus oocyte maturation of store-operated Ca(2+) entry (SOCE), an important Ca(2+) influx pathway in oocytes and other nonexcitable cells. We have previously shown that SOCE inactivates during Xenopus oocyte meiosis. SOCE inactivation may be important in preventing premature egg activation. In this study, we investigated the correlation between SOCE inactivation and the Mos-mitogen-activated protein kinase (MAPK)-maturation promoting factor (MPF) kinase cascade, which drives Xenopus oocyte maturation. SOCE inactivation at germinal vesicle breakdown coincides with an increase in the levels of MAPK and MPF. By differentially inducing Mos, MAPK, and MPF, we demonstrate that the activation of MPF is necessary for SOCE inactivation during oocyte maturation. In contrast, sustained high levels of Mos kinase and the MAPK cascade have no effect on SOCE activation. We further show that preactivated SOCE is not inactivated by MPF, suggesting that MPF does not block Ca(2+) influx through SOCE channels, but rather inhibits coupling between store depletion and SOCE activation. PMID- 11781336 TI - Characterization of Cep135, a novel coiled-coil centrosomal protein involved in microtubule organization in mammalian cells. AB - By using monoclonal antibodies raised against isolated clam centrosomes, we have identified a novel 135-kD centrosomal protein (Cep135), present in a wide range of organisms. Cep135 is located at the centrosome throughout the cell cycle, and localization is independent of the microtubule network. It distributes throughout the centrosomal area in association with the electron-dense material surrounding centrioles. Sequence analysis of cDNA isolated from CHO cells predicted a protein of 1,145-amino acid residues with extensive alpha-helical domains. Expression of a series of deletion constructs revealed the presence of three independent centrosome-targeting domains. Overexpression of Cep135 resulted in the accumulation of unique whorl-like particles in both the centrosome and the cytoplasm. Although their size, shape, and number varied according to the level of protein expression, these whorls were composed of parallel dense lines arranged in a 6-nm space. Altered levels of Cep135 by protein overexpression and/or suppression of endogenous Cep135 by RNA interference caused disorganization of interphase and mitotic spindle microtubules. Thus, Cep135 may play an important role in the centrosomal function of organizing microtubules in mammalian cells. PMID- 11781337 TI - Smitin, a novel smooth muscle titin-like protein, interacts with myosin filaments in vivo and in vitro. AB - Smooth muscle cells use an actin-myosin II-based contractile apparatus to produce force for a variety of physiological functions, including blood pressure regulation and gut peristalsis. The organization of the smooth muscle contractile apparatus resembles that of striated skeletal and cardiac muscle, but remains much more poorly understood. We have found that avian vascular and visceral smooth muscles contain a novel, megadalton protein, smitin, that is similar to striated muscle titin in molecular morphology, localization in a contractile apparatus, and ability to interact with myosin filaments. Smitin, like titin, is a long fibrous molecule with a globular domain on one end. Specific reactivities of an anti-smitin polyclonal antibody and an anti-titin monoclonal antibody suggest that smitin and titin are distinct proteins rather than differentially spliced isoforms encoded by the same gene. Smitin immunofluorescently colocalizes with myosin in chicken gizzard smooth muscle, and interacts with two configurations of smooth muscle myosin filaments in vitro. In physiological ionic strength conditions, smitin and smooth muscle myosin coassemble into irregular aggregates containing large sidepolar myosin filaments. In low ionic strength conditions, smitin and smooth muscle myosin form highly ordered structures containing linear and polygonal end-to-end and side-by-side arrays of small bipolar myosin filaments. We have used immunogold localization and sucrose density gradient cosedimentation analyses to confirm association of smitin with both the sidepolar and bipolar smooth muscle myosin filaments. These findings suggest that the titin-like protein smitin may play a central role in organizing myosin filaments in the contractile apparatus and perhaps in other structures in smooth muscle cells. PMID- 11781338 TI - The carboxyl-terminal isoforms of smooth muscle myosin heavy chain determine thick filament assembly properties. AB - The alternatively spliced SM1 and SM2 smooth muscle myosin heavy chains differ at their respective carboxyl termini by 43 versus 9 unique amino acids. To determine whether these tailpieces affect filament assembly, SM1 and SM2 myosins, the rod region of these myosin isoforms, and a rod with no tailpiece (tailless), were expressed in Sf 9 cells. Paracrystals formed from SM1 and SM2 rod fragments showed different modes of molecular packing, indicating that the tailpieces can influence filament structure. The SM2 rod was less able to assemble into stable filaments than either SM1 or the tailless rods. Expressed full-length SM1 and SM2 myosins showed solubility differences comparable to the rods, establishing the validity of the latter as a model for filament assembly. Formation of homodimers of SM1 and SM2 rods was favored over the heterodimer in cells coinfected with both viruses, compared with mixtures of the two heavy chains renatured in vitro. These results demonstrate for the first time that the smooth muscle myosin tailpieces differentially affect filament assembly, and suggest that homogeneous thick filaments containing SM1 or SM2 myosin could serve distinct functions within smooth muscle cells. PMID- 11781339 TI - p38 MAP kinase negatively regulates endothelial cell survival, proliferation, and differentiation in FGF-2-stimulated angiogenesis. AB - The p38 mitogen-activated protein kinase (p38) is activated in response to environmental stress and inflammatory cytokines. Although several growth factors, including fibroblast growth factor (FGF)-2, mediate activation of p38, the consequences for growth factor-dependent cellular functions have not been well defined. We investigated the role of p38 activation in FGF-2-induced angiogenesis. In collagen gel cultures, bovine capillary endothelial cells formed tubular growth-arrested structures in response to FGF-2. In these collagen gel cultures, p38 activation was induced more potently by FGF-2 treatment compared with that in proliferating cultures. Treatment with the p38 inhibitor SB202190 enhanced FGF-2-induced tubular morphogenesis by decreasing apoptosis, increasing DNA synthesis and cell proliferation, and enhancing the kinetics of cell differentiation including increased expression of the Notch ligand Jagged1. Overexpression of dominant negative mutants of the p38-activating kinases MKK3 and MKK6 also supported FGF-2-induced tubular morphogenesis. Sustained activation of p38 by FGF-2 was identified in vascular endothelial cells in vivo in the chick chorioallantoic membrane (CAM). SB202190 treatment enhanced FGF-2-induced neovascularization in the CAM, but the vessels displayed abnormal features indicative of hyperplasia of endothelial cells. These results implicate p38 in organization of new vessels and suggest that p38 is an essential regulator of FGF 2-driven angiogenesis. PMID- 11781341 TI - Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. AB - Using flow cytometry and single cell-based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self renewing pluripotent stem cells persist in the developing mouse liver and that such cells can be induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system. PMID- 11781342 TI - Killing the messenger: new insights into nonsense-mediated mRNA decay. PMID- 11781340 TI - The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure. AB - Chemokines are small cytokines primarily known for their roles in inflammation. More recently, however, they have been implicated in processes involved in development of the granulation tissue of wounds, but little is known about their functions during this process. Fibroblasts play key roles in this phase of healing: some fibroblasts differentiate into myofibroblasts, alpha-smooth muscle actin (SMA)-producing cells that are important in wound closure and contraction. Here we show that the CXC chemokine chicken chemotactic and angiogenic factor (cCAF) stimulates fibroblasts to produce high levels of alpha-SMA and to contract collagen gels more effectively than do normal fibroblasts, both characteristic properties of myofibroblasts. Specific inhibition of alpha-SMA expression resulted in abrogation of cCAF-induced contraction. Furthermore, application of cCAF to wounds in vivo increases the number of myofibroblasts present in the granulation tissue and accelerates wound closure and contraction. We also show that these effects in culture and in vivo can be achieved by a peptide containing the NH2-terminal 15 amino acids of the cCAF protein and that inhibition of alpha SMA expression also results in inhibition of N-peptide-induced collagen gel contraction. We propose that chemokines are major contributors for the differentiation of fibroblasts into myofibroblasts during formation of the repair tissue. Because myofibroblasts are important in many pathological conditions, and because chemokines and their receptors are amenable to pharmacological manipulations, chemokine stimulation of myofibroblast differentiation may have implications for modulation of functions of these cells in vivo. PMID- 11781343 TI - Stimulation and inhibition of immune responses: an intricate balancing act. PMID- 11781344 TI - Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases. PMID- 11781345 TI - Pituitary adenomas in man and mouse: oncogenic potential of a truncated fibroblast growth factor receptor 4. PMID- 11781346 TI - The buzz about BAFF. PMID- 11781347 TI - Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. AB - Pneumococcus is the most common and aggressive cause of bacterial meningitis and induces a novel apoptosis-inducing factor-dependent (AIF-dependent) form of brain cell apoptosis. Loss of production of two pneumococcal toxins, pneumolysin and H(2)O(2), eliminated mitochondrial damage and apoptosis. Purified pneumolysin or H(2)O(2) induced microglial and neuronal apoptosis in vitro. Both toxins induced increases of intracellular Ca(2+) and triggered the release of AIF from mitochondria. Chelating Ca(2+) effectively blocked AIF release and cell death. In experimental pneumococcal meningitis, pneumolysin colocalized with apoptotic neurons of the hippocampus, and infection with pneumococci unable to produce pneumolysin and H(2)O(2) significantly reduced damage. Two bacterial toxins, pneumolysin and, to a lesser extent, H(2)O(2), induce apoptosis by translocation of AIF, suggesting new neuroprotective strategies for pneumococcal meningitis. PMID- 11781348 TI - Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. AB - IL-9 is a pleiotropic cytokine with multiple functions on many cell types involved in the pathology of human asthma. The constitutive overexpression of IL 9 in the lungs of transgenic mice resulted in an asthma-like phenotype. To define the contribution of IL-9 to lung inflammation we generated transgenic mice in which lung-specific expression of the IL-9 transgene is inducible by doxycycline. Transgene induction resulted in lymphocytic and eosinophilic infiltration of the lung, airway epithelial cell hypertrophy with mucus production, and mast cell hyperplasia, similar to that seen in mice that constitutively expressed IL-9 in their lungs. Various cytokines, including IL-4, IL-5, and IL-13, were expressed in the lung in response to IL-9. Blockade of IL-4 or IL-5 following IL-9 induction reduced airway eosinophilia without affecting mucus production. In contrast, neutralization of IL-13 completely abolished both lung inflammation and mucus production. These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully. PMID- 11781353 TI - Presented antigen from damaged pancreatic beta cells activates autoreactive T cells in virus-mediated autoimmune diabetes. AB - The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged beta cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice harboring a diabetogenic T cell repertoire with either the islet-damaging agent streptozotocin (STZ) or poly I:C, which nonspecifically activates T cells. Significantly, only treatment of mice with STZ resulted in IDDM and mimicked the effects observed following CB4 infection. Furthermore, antigen-presenting cells from STZ-treated mice were shown to directly activate autoreactive T cells and induce diabetes. Therefore, the primary role of CB4 in the precipitation of IDDM is to damage tissue, causing release and presentation of sequestered islet antigen. These events stimulate autoreactive T cells and thereby initiate disease. PMID- 11781350 TI - Human HTm4 is a hematopoietic cell cycle regulator. AB - Proper control of cell cycle progression is critical for the constant self renewal, differentiation, and homeostasis of the hematopoietic system. Cells of all types share the common cell cycle regulators. The different expression patterns of common regulators, in a broad sense, define cell-type or lineage specificity. However, there remains the possibility of hematopoietic cell cycle regulators tailored to the demands of the hematopoietic system. Here we describe a novel protein, HTm4, which serves as a hematopoietic cell cycle regulator. Our data indicate that HTm4 is expressed in hematopoietic tissues and is tightly regulated during the differentiation of hematopoietic stem cells. It binds to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes, and the three proteins demonstrate similar patterns of cellular expression in human lymphoid tissues. HTm4 stimulates the phosphatase activity of KAP, and its C-terminal region is required for binding to KAP-CDK2 complexes and the modulation of KAP activity. Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition. PMID- 11781352 TI - Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis. AB - It is estimated that up to one in five individuals develop pituitary gland tumors. Despite the common occurrence of these tumors, the pathogenetic mechanisms underlying their development remain largely unknown. We report the identification of a novel pituitary tumor-derived, N-terminally truncated isoform of FGF receptor-4 (ptd-FGFR4). The corresponding mRNA results from alternative transcription initiation and encodes a polypeptide that lacks a signal peptide and the first two extracellular Ig-like domains. ptd-FGFR4 has a distinctive cytoplasmic residence, is constitutively phosphorylated, and is transforming in vitro and in vivo. Here we show that targeted expression of ptd-FGFR4, but not FGFR4, results in pituitary tumors that morphologically recapitulate the human disease. PMID- 11781349 TI - Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. AB - Ingestion of apoptotic cells in vitro by macrophages induces TGF-beta1 secretion, resulting in an anti-inflammatory effect and suppression of proinflammatory mediators. Here, we show in vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation. This enhancement appeared to require phosphatidylserine (PS) on the apoptotic cells and local induction of TGF beta1. Working with thioglycollate-stimulated peritonea or LPS-stimulated lungs, we examined the effect of apoptotic cell uptake on TGF-beta1 induction. Viable or opsonized apoptotic human Jurkat T cells, or apoptotic PLB-985 cells, human monomyelocytes that do not express PS during apoptosis, failed to induce TGF beta1. PS liposomes, or PS directly transferred onto the PLB-985 surface membranes, restored the TGF-beta1 induction. Apoptotic cell instillation into LPS stimulated lungs reduced proinflammatory chemokine levels in the bronchoalveolar lavage fluid (BALF). Additionally, total inflammatory cell counts in the BALF were markedly reduced 1-5 days after apoptotic cell instillation, an effect that could be reversed by opsonization or coinstillation of TGF-beta1 neutralizing antibody. This reduction resulted from early decrease in neutrophils and later decreases in lymphocytes and macrophages. In conclusion, apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-beta1 secretion, resulting in accelerated resolution of inflammation. PMID- 11781355 TI - Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. AB - To investigate the consequence of deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI), we generated homozygous TAFI-deficient mice by targeted gene disruption. Intercrossing of heterozygous TAFI mice produced offspring in the expected Mendelian ratio, indicating that transmission of the mutant TAFI allele did not lead to embryonic lethality. TAFI-deficient mice developed normally, reached adulthood, and were fertile. No gross physical abnormalities were observed up to 24 months of age. Hematological analysis of TAFI-deficient mice did not show any major differences including plasma fibrinogen level, prothrombin time, and activated partial thromboplastin time. TAFI-deficient mice did not suffer from excess bleeding as determined by blood loss following tail transection, although their plasma failed to prolong clot lysis time in vitro. In vivo, TAFI deficiency did not influence occlusion time in either an arterial or a venous injury model. TAFI deficiency did not improve survival rate compared with the wild-type in thrombin-induced thromboembolism, factor X coagulant protein induced thrombosis, and endotoxin-induced disseminated intravascular coagulation. Furthermore, TAFI deficiency did not alter kaolin-induced writhing response, implying that TAFI does not play a major role in bradykinin catabolism. The current study demonstrates that TAFI deficiency does not change normal responses to acute challenges. PMID- 11781351 TI - Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome. AB - BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjogren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis. PMID- 11781354 TI - Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin. AB - Metabolic acidosis causes a reversal of polarity of HCO(3)(-) flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, beta intercalated (HCO(3)(-)-secreting) cells are remodeled to functionally resemble alpha-intercalated (H(+)-secreting) cells. A similar remodeling of beta intercalated cells, in which the polarity of H(+) pumps and Cl(-)/HCO(3)(-) exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO(3)(-) flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO(3) exchange was abolished following acid incubation. Some cells also developed basolateral Cl(-)/HCO(3)(-) exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti hensin antibodies prevented the acid-induced changes in apical and basolateral Cl(-)/HCO(3)(-) exchange observed in the same cells and the corresponding suppression of HCO(3)(-) secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin. PMID- 11781357 TI - The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. AB - Recent evidence has defined an important role for PPARalpha in the transcriptional control of cardiac energy metabolism. To investigate the role of PPARalpha in the genesis of the metabolic and functional derangements of diabetic cardiomyopathy, mice with cardiac-restricted overexpression of PPARalpha (MHC PPAR) were produced and characterized. The expression of PPARalpha target genes involved in cardiac fatty acid uptake and oxidation pathways was increased in MHC PPAR mice. Surprisingly, the expression of genes involved in glucose transport and utilization was reciprocally repressed in MHC-PPAR hearts. Consistent with the gene expression profile, myocardial fatty acid oxidation rates were increased and glucose uptake and oxidation decreased in MHC-PPAR mice, a metabolic phenotype strikingly similar to that of the diabetic heart. MHC-PPAR hearts exhibited signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and transgene expression-dependent alteration in systolic ventricular dysfunction. These results demonstrate that (a) PPARalpha is a critical regulator of myocardial fatty acid uptake and utilization, (b) activation of cardiac PPARalpha regulatory pathways results in a reciprocal repression of glucose uptake and utilization pathways, and (c) derangements in myocardial energy metabolism typical of the diabetic heart can become maladaptive, leading to cardiomyopathy. PMID- 11781363 TI - Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein. AB - The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in approximately 170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2-mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection. PMID- 11781359 TI - Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. AB - A critical component of insulin action is the enzyme phosphoinositide (PI) 3 kinase. The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene. Heterozygous disruption of Pik3r1 improves insulin signaling and glucose homeostasis in normal mice and mice made insulin-resistant by heterozygous deletion of the Insulin receptor and/or insulin receptor substrate-1 (IRS1) genes. Reduced expression of p85 modulates the molecular balance between this protein, the p110 catalytic subunit of PI 3 kinase, and the IRS proteins. Thus, despite the decrease in p85alpha, PI 3-kinase activation is normal, insulin-stimulated Akt activity is increased, and glucose tolerance and insulin sensitivity are improved. Furthermore, Pik3r1 heterozygosity protects mice with genetic insulin resistance from developing diabetes. These data suggest that regulation of p85alpha levels may provide a novel therapeutic target for the treatment of type 2 diabetes. PMID- 11781364 TI - Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer cell functions. AB - Infection with hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Little is known about how this virus is able to persist or whether this persistence might be because of its ability to alter the early innate immune response. The major HCV envelope protein E2 has been shown to bind to CD81. Thus, HCV binding to natural killer (NK) cells could result in the cross linking of CD81. To explore this possibility, we investigated whether cross linking CD81 on NK cells could alter NK cell function. CD81 cross-linking by monoclonal antibody (mAb) specific for CD81 or by immobilized E2 have been shown to result in costimulatory signals for human T cells. In this study, we show that CD81 cross-linking via immobilized E2 or mAbs specific for CD81 inhibits not only non major histocompatibility complex-restricted cytotoxicity mediated by NK cells but also interferon (IFN)-gamma production by NK cells after exposure to interleukin (IL)-2, IL-12, IL-15, or CD16 cross-linking. These results show that CD81 cross-linking mediates completely different signals in NK cells versus T cells. Importantly, these results suggest that one mechanism whereby HCV can alter host defenses and innate immunity is via the early inhibition of IFN-gamma production by NK cells. PMID- 11781360 TI - Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. AB - Immature bone marrow-derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae. After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice. Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype. PMID- 11781356 TI - Diabetic LDL inhibits cell-cycle progression via STAT5B and p21(waf). AB - Modified LDL is a major cause of injury to the endothelium in diabetes. In the present study, we analyzed the effects on endothelial cells of LDL recovered from type 2 diabetic patients (dm-LDL) or from nondiabetic subjects (n-LDL). Treatment of human umbilical vein endothelial cells with dm-LDL, but not n-LDL, led to the accumulation of cells in G1. To dissect the molecular mechanisms of this effect, we analyzed the expression and function of the cyclin-dependent kinase inhibitor p21(waf), a cell cycle regulator known to be a target of the signal transducers and activators of transcription (STATs). dm-LDL led to transient STAT5 phosphorylation and the formation of a STAT5-containing complex and activated p21(waf) expression at the transcriptional level. Expression of the dominant negative form of STAT5B, but not of STAT5A, significantly decreased both p21(waf) expression and the fraction of cells in G1. Finally, immunofluorescence analysis demonstrated that activated STAT5 is expressed in newly formed intraplaque vessels and in endothelial cells lining the luminal side of the plaque. Similarly, p21(waf) immunoreactivity was found in the neointimal vasculature. Our results suggest a role of STAT5B as a regulator of gene expression in diabetes associated vascular disease. PMID- 11781362 TI - Plasmodium falciparum phospholipase C hydrolyzing sphingomyelin and lysocholinephospholipids is a possible target for malaria chemotherapy. AB - Sphingomyelinase (SMase) is one of the principal enzymes in sphingomyelin (SM) metabolism. Here, we identified a Plasmodium falciparum gene (PfNSM) encoding a 46-kD protein, the amino acid sequence of which is approximately 25% identical to that of bacteria SMases. Biochemical analyses of the recombinant protein GST PfNSM, a fusion protein of the PfNSM product with glutathione-S-transferase, reveal that this enzyme retained similar characteristics in various aspects to SMase detected in P. falciparum-infected erythrocytes and isolated parasites. In addition, the recombinant protein retains hydrolyzing activity not only of SM but also of lysocholinephospholipids (LCPL) including lysophosphatidylcholine and lysoplatelet-activating factor, indicating that PfNSM encodes SM/LCPL phospholipase C (PLC). Scyphostatin inhibited SM/LCPL-PLC activities of the PfNSM product as well as the intraerythrocytic proliferation of P. falciparum in a dose dependent manner with ID(50) values for SM/LCPL-PLC activities and the parasite growth at 3-5 microM and approximately 7 microM, respectively. Morphological analysis demonstrated most severe impairment in the intraerythrocytic development with the addition of scyphostatin at trophozoite stage than at ring or schizont stages, suggesting its effect specifically on the stage progression from trophozoite to schizont, coinciding with the active transcription of PfNSM gene. PMID- 11781365 TI - The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. AB - Interleukin (IL)-9 is a pleiotropic cytokine secreted by T helper (Th)2 cells and has been proposed as a candidate gene for asthma and allergy. We have used mice genetically deficient in IL-9 to determine the role of this cytokine in the pathophysiologic features of the allergic pulmonary response-airway hyperreactivity (AHR) and eosinophilia. We have demonstrated that IL-9 is not required for the development of a robust Th2 response to allergen in sensitized mice. IL-9 knockout mice developed a similar degree of eosinophilic inflammation and AHR to their wild-type littermates. Goblet cell hyperplasia and immunoglobulin (Ig) E production were also unaffected by the lack of IL-9. Moreover, levels of bronchoalveolar lavage (BAL) IL-4, IL-5, and IL-13 were comparable between wild-type and knockout mice. These findings indicate that IL-9 is not obligatory for the development of eosinophilia and AHR, and imply that other Th2 cytokines can act in a compensatory fashion. PMID- 11781358 TI - Multiple immuno-regulatory defects in type-1 diabetes. AB - Susceptibility to immune-mediated diabetes (IMD) in humans and NOD mice involves their inherently defective T cell immunoregulatory abilities. We have followed natural killer (NK) T cell numbers in patients with IMD, both by flow cytometry using mAbs to the characteristic junctions found in the T cell receptors of this cell subtype, and by semiquantitative RT-PCR for the corresponding transcripts. Both before and after clinical onset, the representation of these cells in patients' PBMCs is reduced. We also report low numbers of resting CD4(+) CD25(+) T cells in IMD patients, a subset of T cells shown to have important immunoregulatory functions in abrogating autoimmunities in 3-day thymectomized experimental mice. Whereas a biased Th1 to Th2 cytokine profile has been suggested to underlie the pathogenesis of IMD in both species, we found defective production of IFN-gamma in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-gamma and IL-4 deficiencies in V(alpha)24(+) NK T-enriched cells. These data suggest that multiple immunoregulatory T (Treg) cell defects underlie islet cell autoimmunity leading to IMD in humans and that these lesions may be part of a broad T cell defect. PMID- 11781361 TI - Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. AB - Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-alpha (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-alpha induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild type led to the induction of peptide-specific predominantly interleukin (IL)-10 producing CD4(+) T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF alpha results in incompletely matured DCs (semi-mature DCs) which induce peptide specific IL-10-producing T cells in vivo and prevent EAE. PMID- 11781368 TI - V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. AB - Most lymphoid malignancies are initiated by specific chromosomal translocations between immunoglobulin (Ig)/T cell receptor (TCR) gene segments and cellular proto-oncogenes. In many cases, illegitimate V(D)J recombination has been proposed to be involved in the translocation process, but this has never been functionally established. Using extra-chromosomal recombination assays, we determined the ability of several proto-oncogenes to target V(D)J recombination, and assessed the impact of their recombinogenic potential on translocation rates in vivo. Our data support the involvement of 2 distinct mechanisms: translocations involving LMO2, TAL2, and TAL1 in T cell acute lymphoblastic leukemia (T-ALL), are compatible with illegitimate V(D)J recombination between a TCR locus and a proto-oncogene locus bearing a fortuitous but functional recombination site (type 1); in contrast, translocations involving BCL1 and BCL2 in B cell non-Hodgkin's lymphomas (B-NHL), are compatible with a process in which only the IgH locus breaks are mediated by V(D)J recombination (type 2). Most importantly, we show that the t(11;14)(p13;q32) translocation involving LMO2 is present at strikingly high frequency in normal human thymus, and that the recombinogenic potential conferred by the LMO2 cryptic site is directly predictive of the in vivo level of translocation at that locus. These findings provide new insights into the regulation forces acting upon genomic instability in B and T cell tumorigenesis. PMID- 11781369 TI - Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. AB - Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow-derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2-deficient mice were still susceptible to sHA. In accordance, addition of an anti-TLR-4 mAb to human monocyte-derived DCs blocked sHA-induced tumor necrosis factor alpha production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-kappa B, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs. PMID- 11781366 TI - Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. AB - Receptor-stimulated generation of reactive oxygen species (ROS) has been shown to regulate signal transduction, and previous studies have suggested that T cell receptor (TCR) signals may involve or be sensitive to ROS. In this study, we have shown for the first time that TCR cross-linking induced rapid (within 15 min) generation of both hydrogen peroxide and superoxide anion, as defined with oxidation-sensitive dyes, selective pharmacologic antioxidants, and overexpression of specific antioxidant enzymes. Furthermore, the data suggest the novel observation that superoxide anion and hydrogen peroxide are produced separately by distinct TCR-stimulated pathways. Unexpectedly, TCR-stimulated activation of the Fas ligand (FasL) promoter and subsequent cell death was dependent upon superoxide anion, but independent of hydrogen peroxide, while nuclear factor of activated T cells (NFAT) activation or interleukin 2 transcription was independent of all ROS. Anti-CD3 induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2 required hydrogen peroxide generation but was unaffected by superoxide anion. Thus, antigen receptor signaling induces generation of discrete species of oxidants that selectively regulate two distinct redox sensitive pathways, a proapoptotic (FasL) and a proliferative pathway (ERK). PMID- 11781367 TI - T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis. AB - Dysregulated T cell responses to enteric bacteria have been implicated as a common mechanism underlying pathogenesis in rodent models of colitis. However, the bacterial species and T cell specificities that induce disease have been poorly defined. We have developed a model system in which target antigen, bacterial host, and corresponding T cell specificity are defined. OVA-specific T cells from DO11.RAG-2(-/-) TCR transgenic mice were transferred into RAG-2(-/-) recipients whose intestinal tracts were colonized with OVA-expressing or control Escherichia coli. Transfer of antigen-naive DO11.RAG-2(-/-) T cells into recipients colonized with OVA-E. coli resulted in enhanced intestinal recruitment and cell cycling of OVA-specific T cells; however, there was no development of disease. In contrast, transfer of polarized T helper (Th) 1 and Th2 populations resulted in severe wasting and colitis in recipients colonized with OVA expressing but not control E. coli. The histopathologic features of disease induced by Th1 and Th2 transfers were distinct, but disease severity was comparable. Induction of disease by both Th1 and Th2 transfers was dependent on bacterially associated OVA. These results establish that a single bacterially associated antigen can drive the progression of colitis mediated by both Th1 and Th2 cells and provide a new model for understanding the immunoregulatory interactions between T cells responsive to gut floral antigens. PMID- 11781370 TI - Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross presented by dendritic cells. AB - Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4(+) and CD8(+) T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4(+) T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2-restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159-167 of PDC-E2, induces specific MHC class I-restricted CD8(+) CTL lines from 10/12 HLA-A2(+) PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2-specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2-specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2-specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen-immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease. PMID- 11781376 TI - Molecular mechanisms of glucocorticoid antiproliferative effects: antagonism of transcription factor activity by glucocorticoid receptor. AB - Glucocorticoids (GCs) exert their anti-inflammatory and immunosuppressive effects by inhibiting the expression of cytokines and adhesion molecules. The molecular basis of GC action lies in their capacity to diffuse through the cell membrane and bind their cytosolic GC receptor (GR), which subsequently undergoes nuclear translocation and modulates transcriptional activation through association with promoter elements, GC response elements (GRE). GR also antagonized the activity of transcription factors, including NF-kappa B, NF-AT, and AP-1, through direct and indirect mechanisms. GCs induced the gene transcription and protein synthesis of the NF-kappa B inhibitor, I kappa B. Activated GR antagonized transcription factor activity through protein:protein interaction. This involved complexing with and inhibition of transcription factor binding to DNA (simple model), association with factor bound at its DNA site (composite model), and/or through interaction of GRE-bound GR with DNA-bound transcription factor (transmodulation model). Finally, GR competed with transcription factors for nuclear coactivators (competition model), including CBP and p300. Remarkably, GR did not affect the assembly of the preinitiation complex but acted proximally in inhibiting transcription factor activity and thus transcriptional initiation. PMID- 11781377 TI - Nutrients and their role in host resistance to infection. AB - Almost all nutrients in the diet play a crucial role in maintaining an "optimal" immune response, such that deficient and excessive intakes can have negative consequences on immune status and susceptibility to a variety of pathogens. Iron and vitamin A deficiencies and protein-energy malnutrition are highly prevalent worldwide and are important to the public health in terms of immunocompetence. There are also nutrients (i.e., glutamine, arginine, fatty acids, vitamin E) that provide additional benefits to immunocompromised persons or patients who suffer from various infections. The remarkable advances in immunology of recent decades have provided insights into the mechanisms responsible for the effects of various nutrients in the diet on specific functions in immune cells. In this review, we will present evidence and proposed mechanisms for the importance of a small group of nutrients that have been demonstrated to affect host resistance to infection will be presented. An inadequate status of some of these nutrients occurs in many populations in the world (i.e., vitamin A, iron, and zinc) where infectious disease is a major health concern. We will also review nutrients that may specifically modulate host defense to infectious pathogens (long-chain polyunsaturated n-3 fatty acids, vitamin E, vitamin C, selenium, and nucleotides). A detailed review of the effect of long-chain polyunsaturated n-3 fatty acids on host defense is provided as an example of how the disciplines of nutrition and immunology have been combined to identify key mechanisms and propose nutrient-directed management of immune-related syndromes. PMID- 11781375 TI - IL-17: prototype member of an emerging cytokine family. AB - IL-17 is a potent proinflammatory cytokine produced by activated memory T cells. The large-scale sequencing of the human and other vertebrate genomes has revealed the presence of additional genes encoding proteins clearly related to IL-17, thus defining a new family of cytokines. There are at least six members of the IL-17 family in humans and in mice. Initial characterization suggests that like IL-17, several of these newly identified molecules have the ability to modulate immune function. Neither the IL-17 family nor the cognate receptors that have been identified for these molecules bear obvious sequence similarity to other known families of proteins. Thus, they represent a distinct signaling system that appears to have been highly conserved across vertebrate evolution. The potent inflammatory actions that have been identified for several of these factors and the emerging associations with major human diseases suggest that these proteins may have significant roles in inflammatory processes. PMID- 11781372 TI - Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues. AB - Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of 'tissue-specific' adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattractant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4(+) effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and alpha 4 beta 7, respectively. We show that within 2 d of systemic immunization CD4(+) T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate alpha 4 beta 7, while those responding to antigen in intestinal lymph nodes selectively express high levels of alpha 4 beta 7 and acquire responsiveness to the intestinal chemokine thymus expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria. PMID- 11781378 TI - Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft-versus-host and host-versus-graft reactivity by anti-CD44v6. AB - T-cell maturation is accelerated in transgenic mice expressing rat CD44v4-v7 on T cells, the effect being blocked by anti-CD44v6. This finding suggested functional activity of CD44v6 in thymocyte development. We tested the hypothesis by antibody blocking and using mice with targeted deletion of CD44v6/v7 exon products (CD44v6/v7(-/-)). When lethally irradiated CD44v6/v7-competent (CD44v6/v7(+/+)) mice were reconstituted syngeneically, higher numbers of CD44v6/v7(-/-) than CD44v6/v7(+/+) BMC were required for survival, the period of reconstitution was prolonged, and regain of immunocompetence was delayed. Similar findings were observed in lethally irradiated, anti-CD44v6-treated syngeneic CD44v6/v7(+/+) hosts. Thus, CD44v6/v7 supports maturation and expansion of hematopoietic progenitor cells. Surprisingly, reconstitution with CD44v6/v7(-/-) BMC or anti CD44v6 treatment of the nonlethally irradiated allogeneic CD44v6/v7(+/+) host had only a minor impact on survival rates. When nonlethally irradiated CD44v6/v7(-/-) hosts received an allogeneic graft, survival rates were improved. These phenomena have been a result of reduced GvH reactivities when the donor was CD44v6/v7(-/-) and reduced HvG reactivities in the CD44v6/v7(-/-) host. Thus, although a deficit or blockade of CD44v6/v7 has a negative impact on hematopoietic reconstitution, a transient blockade will be of benefit for the allogeneically reconstituted host because of a strong reduction in GvH and HvG reactivities. PMID- 11781374 TI - Fc gamma receptors and cross-presentation in dendritic cells. PMID- 11781380 TI - Expression and functional characterization of CFTR in mast cells. AB - Mast cell activation requires Cl(-) flux, which maintains the driving force for entry of extracellular calcium and initiates release of mediators such as histamine. However, chloride channel expression in mast cells has been poorly understood. For the first time, reverse transcriptase-polymerase chain reaction shows that rat-cultured mast cells (RCMC) and peritoneal mast cells (PMC) contain mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR), an important chloride channel. Immunostaining with an anti-CFTR antibody indicates expression of CFTR in PMC and RCMC. Mast cell CFTR is a functional Cl(-) channel because it is capable of mediating Cl(-) flux in response to elevated cAMP. An inhibitor of CFTR-dependent Cl(-) flux, diphenylamine-2-carboxylate down regulates mast cell mediator release. These results show that rat mast cells express a functional CFTR, which might be important in mediator release. PMID- 11781379 TI - Laminin binding to the calreticulin fragment vasostatin regulates endothelial cell function. AB - Vasostatin, the 1-180 amino acids NH(2) domain of calreticulin, inhibits endothelial cell proliferation, angiogenesis, and tumor growth, but the mechanisms underlying these effects are unclear. We show that endothelial cells express the extracellular matrix protein laminin, including chains alpha 5 and gamma 1 and that vasostatin specifically binds to laminin. When added to endothelial cell cultures, vasostatin specifically inhibits endothelial cell attachment to laminin and by this mechanism, can reduce subsequent endothelial cell growth induced by basic fibroblast growth factor. As an angiogenesis inhibitor that specifically disrupts endothelial cell attachment to components of the extracellular matrix, vasostatin has a unique potential as a cancer therapeutic. PMID- 11781382 TI - (-)Epigallocatechin-3-gallate inhibits leukocyte elastase: potential of the phyto factor in hindering inflammation, emphysema, and invasion. AB - Flavanol (-)epigallocatechin-3-gallate is shown to be a potent natural inhibitor of leukocyte elastase that may be used to reduce elastase-mediated progression to emphysema and tumor invasion. This phyto-factor, abundant in green tea, exerts a dose-dependent, noncompetitive inhibition of leukocyte elastase at a noncytotoxic concentration and is effective in neutrophil culture. This inhibition shows an IC(50) of 0.4 microM, 30 times higher than the alpha1-protease inhibitor but lower than other known natural and synthetic elastase inhibitors. The flavanol inhibits leukocyte elastase at concentrations of 50, 150, and 2500 times lower than that effective on gelatinases (MMP-2 and MMP-9), thrombin, and cathepsin G, respectively, and also blocks elastase-mediated activation of MMP-9. PMID- 11781385 TI - Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism. AB - Nramp2 is a widely expressed metal-ion transporter that is involved in dietary iron absorption in the duodenum and iron uptake from transferrin in peripheral tissues. Nramp1 is a related gene involved in regulation of host pathogen interaction. Nramp2 has at least two alternatively spliced isoforms, one of which contains an iron-responsive element in its 3'-untranslated region. In this study, we investigated the regulation of both isoforms of Nramp2 in activated primary macrophages from mouse strains with wild-type (Bcg(r)) or mutant (Bcg(s)) alleles. The Nramp2-IRE and/or -nonIRE transcripts were up-regulated in all mouse strains analyzed after treatment with interferon-gamma and lipopolysaccharide. cDNA microarray analysis revealed that Nramp2 regulation is controlled discordantly from other iron-regulated genes and classical macrophage-activation genes in different mouse strains. We suggest that Nramp2 is regulated independently of known iron-responsive genes in macrophages, and its function in host defense is unrelated to Nramp1. PMID- 11781371 TI - Antitumor monoclonal antibodies enhance cross-presentation ofcCellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. AB - The mechanism of antitumor effect of monoclonal antibodies (mAbs) is not fully understood. Here we show that coating myeloma cells with anti-syndecan-1 antibody promotes cross-presentation of cellular antigens by dendritic cells (DCs) to autologous T cells from healthy donors. The tumor cells treated with anti syndecan-1 or isotype-matched control antibody were fed to HLA-mismatched monocyte-derived immature DCs. Tumor cell-loaded mature DCs induced a strong CD8(+) T cell response that was specific for the cancer-testis (C-T) antigens expressed in the tumor. The CD8(+) T cells killed peptide-pulsed targets, as well as myeloma tumor cells. Importantly, mAbs-coated tumor-loaded DCs were consistently superior to DCs loaded with peptides or dying cells for eliciting tumor-specific killer T cells. This enhanced cross-presentation was not due to enhanced tumor cell uptake or to DC maturation. When mixtures of NY-Eso-1 positive and -negative myeloma cells were captured by DCs, the anti-syndecan-1 antibody had to be on the NY-Eso-1-positive cells to elicit NY-Eso-1-specific response. Cross-presentation was inhibited by pretreatment of DCs with Fc gamma receptor blocking antibodies. Targeting of mAb-coated tumors to DCs may contribute to the efficacy of tumor-reactive mAb and offers a new strategy for immunotherapy. PMID- 11781383 TI - Mycobacterium avium infection of macrophages results in progressive suppression of interleukin-12 production in vitro and in vivo. AB - Interleukin-12 (IL-12) has been shown to have an important role in the host defense against Mycobacterium avium. We sought to determine if human monocyte derived macrophages produce IL-12 upon M. avium infection. Although IL-12 can be measured in supernatants of M. avium-infected macrophages at 24, 48, and 72 h following infection, intracellular staining showed that 24 to 48 h after infection, IL-12 was synthesized chiefly by uninfected macrophages in the monolayer, suggesting that M. avium infection inhibits IL-12 production. In addition, the data also suggest that the longer macrophage monolayers were infected, the less IL-12 they were able to produce. Stimulation of macrophages with IFN-gamma prior to infection with M. avium resulted in greater production of IL-12 compared with unstimulated macrophages. Culture supernatant of M. avium infected macrophage monolayers, but not control macrophages, partially inhibited IL-12 production by IFN-gamma-stimulated macrophages. This partial inhibition was not reversed by anti-interleukin-10 (anti-IL-10) and anti-transforming growth factor beta 1 (anti-TGF beta 1)-neutralizing antibodies. M. avium infection of macrophages in vitro also suppressed IL-12 synthesis induced by Listeria monocytogenes infection. Immunohistochemistry staining of spleen of infected mice showed that IL-12 production by splenic macrophages was more pronounced in the beginning of the infection but decreased later. Our data indicate that M. avium infection of macrophages suppresses IL-12 production by infected cells and that the suppression was not a result of the presence of IL-10 and TGF beta 1 in the culture supernatant. PMID- 11781381 TI - The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages. AB - Apoptosis of neurons and astrocytes has been found in patients undergoing AIDS dementia complex. We demonstrated that supernatants from human primary macrophages (M/M) infected by HIV-1 lead human astroglial cells to oxidative stress, as shown by elevated levels of malondialdehyde, and then to apoptosis. Electron microscopy of astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic blebbing, cytoplasmic loss, and chromatin condensation. Apoptosis was antagonized by pretreating astrocytes with the nonpeptidic superoxide dismutase (SOD) mimetic M40401 but not with anti-HIV-1 compounds, thus showing that apoptosis of astrocytes driven by HIV-1-infected M/M supernatants is mainly mediated by abnormal production of superoxide anions without relationship to HIV-1 replication in such cells. Overall results support the role of oxidative stress mediated by HIV-1-infected M/M as one of the leading causes of neurodegeneration in patients with HIV-1 and suggest the use of nonpeptidic SOD mimetics to counteract HIV-1-related neurological disorders. PMID- 11781386 TI - Shiga toxin 1-induced activation of c-Jun NH(2)-terminal kinase and p38 in the human monocytic cell line THP-1: possible involvement in the production of TNF alpha. AB - Shiga toxin-producing enterohemorrhagic E. coli infections cause bloody diarrhea, which may progress to life-threatening complications such as the hemolytic-uremic syndrome (HUS). HUS patients frequently have elevated levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) detectable in urine. Thus, sequelae may develop following the localized production of proinflammatory cytokines within the kidneys. A possible source of these cytokines are macrophages, which respond to the toxins by producing TNF-alpha. We have shown previously that THP-1 cells produce soluble TNF-alpha in response to the toxins, whose production requires host-cell tyrosine-kinase activity and toxin-enzymatic activity. To further examine signaling pathways involved in TNF alpha expression, we determined that JNK1 and -2 and p38, but not ERK1 or -2, were phosphorylated following toxin exposure. Blockade of p38 activation reduced TNF-alpha production following Shiga toxin 1 treatment. Finally, we present a model of the ribotoxic stress response triggered in human macrophages by Shiga toxins. PMID- 11781373 TI - The B lymphocyte adaptor molecule of 32 kD (Bam32) regulates B cell antigen receptor signaling and cell survival. AB - The B lymphocyte-associated adaptor protein 32 kD in size (Bam32) is expressed at high levels in germinal center (GC) B cells. It has an NH(2)-terminal src homology 2 (SH2) domain which binds phospholipase C (PLC)gamma 2, and a COOH terminal pleckstrin homology (PH) domain. Thus, Bam32 may function to integrate protein tyrosine kinase (PTK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways in B cells. To further define the role Bam32 plays in B cells, we generated Bam32-deficient DT40 cells. These Bam32(-/-) cells exhibited lower levels of B cell antigen receptor (BCR)-induced calcium mobilization with modest decreases in tyrosine phosphorylation of phospholipase C (PLC)gamma 2. Moreover, BCR-induced activation of extracellular signal-regulated kinase (ERK), c-jun NH2 terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways was impaired in Bam32(-/-) cells but not the activation of Akt-related pathways. Activation of downstream transcription factors such as nuclear factor of activated T cells (NF-AT) and nuclear factor of kappa binding (NF-kappa B) was also impaired in Bam32(-/-) cells. Furthermore, Bam32(-/-) cells were more susceptible to BCR-induced death. Taken together, these findings suggest that Bam32 functions to regulate BCR-induced signaling and cell survival most likely in germinal centers. PMID- 11781387 TI - Src kinases regulate PKB activation and modulate cytokine and chemoattractant controlled neutrophil functioning. AB - Tyrosine phosphorylation is thought to be critical in the regulation of neutrophil functioning, and members of the Src family of tyrosine kinases have recently been shown to be regulated in activated granulocytes. We have used a specific pharmacological inhibitor of Src kinases, pyrazolpyrimidine 1 (PP1), to evaluate the role of Src kinases in cytokine/chemoattractant-induced regulation of neutrophil function. PP1 inhibits PKB phosphorylation but not STAT5 phosphorylation or the activation of MAP kinases by fMLP or GM-CSF. Pretreatment of neutrophils with PP1 and with the PI3K inhibitor LY294002 resulted in a strong inhibition of fMLP-induced superoxide production and cytokine-mediated survival but not fMLP-induced migration. It is interesting that the kinetics of inhibition of actin polymerization and the respiratory burst are very similar. Although initiation of both processes was not affected, sustained activation was inhibited by PP1. Taken together, our results demonstrate a critical role for Src kinases in regulating neutrophil cytotoxic-effector functioning through PI3K-PKB. PMID- 11781388 TI - Activation of extracellular signal-related kinase by TNF-alpha controls the maturation and function of murine dendritic cells. AB - Functional roles of extracellular signal-related kinase (ERK) activation in dendritic-cell (DC) maturation have been unclear. In the present study, we investigated the ERK pathway in tumor necrosis factor (TNF)-alpha-induced maturation of murine spleen-derived DC. TNF-alpha increased surface expressions of major histocompatibility (MHC) and costimulatory molecules on DC in a dose dependent manner. High (40 ng/ml) and low (0.4 ng/ml) concentrations of TNF-alpha markedly enhanced ERK1/2 activation in DC, and this activation was blocked completely by PD98059, a selective inhibitor of the ERK pathway. When DC were treated with TNF-alpha at a low but not a high concentration, PD98059 notably enhanced surface expressions of the MHC and costimulatory molecules and allostimulatory capability of the DC. Interleukin (IL)-12 production was enhanced significantly by PD98059 in DC treated with low or high concentration of TNF alpha. These findings suggest that TNF-alpha-induced ERK activation negatively controls maturation and IL-12 production in murine DC. PMID- 11781389 TI - Identification of human CD93 as the phagocytic C1q receptor (C1qRp) by expression cloning. AB - CD93 is a approximately 120 kDa O-sialoglycoprotein that within the hematopoietic system is selectively expressed on cells of the myeloid lineage. So far, its primary structure and function were unknown. We used retroviral-expression cloning to isolate the CD93 cDNA. Sequence analysis revealed that CD93 is identical to a protein on human phagocytes termed C1q receptor (C1qRp). C1qRp was shown previously to mediate enhancement of phagocytosis in monocytes and was suggested to be a receptor of C1q and two other structurally related molecules. When studying CD93 transductants and control cells, we found that cells expressing CD93 have enhanced capacity to bind C1q. Furthermore, we show that immature dendritic cells (DC) express CD93/C1qRp, and mature DC, known to have reduced capacity for antigen uptake and to have lost the ability to phagocytose, show weak-to-negative CD93/C1qRp expression. PMID- 11781384 TI - Regulation of gelatinase B in human monocytic and endothelial cells by PECAM-1 ligation and its modulation by interferon-beta. AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and gelatinase B are coexpressed at sites of inflammation, where an intense interaction occurs between leukocytes and endothelial cells. To investigate whether a functional link exists between PECAM-1 activation and gelatinase B production, the regulatory role of PECAM-1, IFN-gamma, IFN-beta, LPS, and PMA on the production of gelatinase B (MMP-9) was studied in vitro in normal human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs), and in a human monocytic leukemia cell line. In THP-1 cells, progelatinase B levels were slightly up-regulated by immobilized PECAM-1-specific monoclonal antibody (mAb) and soluble recombinant PECAM-1 when compared with strong induction by LPS and PMA. IFN-beta inhibited the induced and basal gelatinase B production but had no modulating effect on the expression of PECAM-1. HUVECs mainly produced progelatinase A (proMMP-2). Treatment with LPS and triggering of the endothelial cells with PECAM-1 mAb or recombinant PECAM-1 had no effect on gelatinase A or B production, whereas PMA stimulated the production of progelatinase B. IFN-beta significantly up-regulated the expression of PECAM-1 in HUVECs but did not affect gelatinase secretion. Finally, in PBMCs, progelatinase B production was increased by soluble PECAM-1 mAb, recombinant PECAM-1, LPS, and PMA, whereas IFN-beta reduced gelatinase B secretion. IFN-beta did not alter PECAM-1 expression on PBMCs. Thus, PECAM-1 and gelatinase B are differently regulated in leukocytes and endothelial cells. PMID- 11781392 TI - AP-1 is essential for p67(phox) promoter activity. AB - The cytosolic NADPH oxidase cofactor p67(phox) has been shown to be one of the limiting factors in assembly and activation of this multi-protein enzyme complex and, therefore, must be highly regulated at the transcriptional level. In the present studies, we have further characterized the promoter for human p67(phox). Genomic sequence upstream of the translational start site (TLS; 2 kb) was cloned, and RACE was used to identify and compare the transcriptional start site (TSS) in two myeloid cell lines, HL-60 and PLB-985. Two major TSS were identified within the first intron for both cell lines, and one transcript isolated from PLB-985 cells started approximately 34 bp 5' of exon 1 and contained no intron 1 sequence. To identify regulatory regions of the promoter, a luciferase reporter was used to assay a series of promoter deletion constructs. The greatest transcriptional activity was observed for fragments containing at least 500 bp upstream of the TLS. Sequence analysis of the p67(phox) promoter revealed consensus binding sites for previously described transcription factors including AP-1 and PU.1. Site-directed mutagenesis of the AP-1 site demonstrated that this site was essential for basal transcription. EMSA, competition, and super-shift assays showed that this site was specifically recognized by nuclear factors of the AP-1 family. EMSA analysis and promoter-reporter assays with the PU.1 consensus sites at positions -176, -283, and -328 demonstrate that PU.1 binds the site at position -283 with high affinity. Mutagenesis of any one of the PU.1 sites reduced the basal transcriptional activity by approximately 50%, demonstrating that, although none of these sites is singularly responsible for the basal transcriptional activity, all three sites play some role in the transcriptional activity of the p67(phox) promoter. In support of this conclusion, mutagenesis of all three sites completely abrogated transcriptional activity. PMID- 11781391 TI - NF-kappa B-mediated transcriptional regulation of human beta-defensin-2 gene following lipopolysaccharide stimulation. AB - beta-Defensins are cationic peptides with broad-spectrum antimicrobial activities that contribute to innate host defense. Among human beta-defensins (hBDs), hBD-2 is up-regulated in epithelial tissues and mononuclear phagocytes in response to bacterial infection and proinflammatory cytokines. However, little is known about the molecular mechanism of hBD-2 gene regulation. Here, we investigated lipopolysaccharide (LPS)-mediated transcriptional regulation of the hBD-2 gene by focusing on the roles of NF-kappa B, STAT, and NF-IL-6 sites in mononuclear phagocytes using RAW264.7 cells, which are sensitive to LPS. Luciferase reporter analyses demonstrated that two NF-kappa B sites were essential for full LPS responsiveness of the hBD-2 gene. Further, both NF-kappa B sites were also crucial for basal transcriptional activity. In contrast, neither the NF-IL-6 nor STAT binding site was required for LPS-induced hBD-2 transcription. Electrophoretic mobility shift assay indicated that in unstimulated cells, NF kappa B p50 homodimer bound to both NF-kappa B sites, whereas the p65-p50 heterodimer formed complexes with these sites following LPS stimulation. Together, these observations indicate that NF-kappa B plays an important role in the regulation of hBD-2 gene expression in response to LPS. PMID- 11781394 TI - Idiopathic intracranial hypertension: an answer to, "the chicken or the egg?". PMID- 11781390 TI - Potential role for Duffy antigen chemokine-binding protein in angiogenesis and maintenance of homeostasis in response to stress. AB - CXC chemokines, which induce angiogenesis, have glutamine-leucine-arginine amino acid residues (ELR motif) in the amino terminus and bind CXCR2 and the Duffy antigen chemokine-binding protein. Duffy, a seven transmembrane protein that binds CXC and CC chemokines, has not been shown to couple to trimeric G proteins or to transduce intracellular signals, although it is highly expressed on red blood cells, endothelial cells undergoing neovascularization, and neuronal cells. The binding of chemokines by Duffy could modulate chemokine responses positively or negatively. Positive regulation could come through the presentation of chemokine to functional receptors, and negative regulation could come through Duffy competition with functional chemokine receptors for chemokine binding, thus serving as a decoy receptor. To determine whether Duffy has a role in angiogenesis and/or maintenance of homeostasis, we developed transgenic mice expressing mDuffy under the control of the preproendothelin promoter/enhancer (PPEP), which directs expression of the transgene to the endothelium. Two PPEP mDuffy-transgenic founders were identified, and expression of the transgene in the endothelium was verified by Northern blot, RT-PCR, and immunostaining of tissues. The phenotype of the mice carrying the transgene appeared normal by all visual parameters. However, careful comparison of transgenic and nontransgenic mice revealed two phenotypic differences: mDuffy-transgenic mice exhibited a diminished angiogenic response to MIP-2 in the corneal micropocket assay, and mDuffy-transgenic mice exhibited enhanced hepatocellular toxicity and necrosis as compared with nontransgenic littermates in response to overdose of acetaminophen (APAP; 400 mg/kg body weight). Morover, APAP treatment was lethal in 50% of the mDuffy-transgenic mice 24 h post challenge, and 100% of the nontransgenic littermates survived this treatment at the 24 h time point. Our data suggest that enhanced expression of mDuffy on endothelial cells can lead to impaired angiogenic response to chemokines and impaired maintenance of homeostasis in response to toxic stresses. PMID- 11781396 TI - Infections and MS: clinical trials move to center stage. PMID- 11781397 TI - Brain death: still-unresolved issues worldwide. PMID- 11781398 TI - Practice parameter: initiation of treatment for Parkinson's disease: an evidence based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. AB - In 1993, the last AAN Practice Parameter on medical treatment of Parkinson's disease (PD) concluded that levodopa was the most effective drug for management of this disorder. Since then, a number of new compounds including non-ergot dopamine agonists (DA) and sustained-release levodopa have been released and studied. Thus, the issue of treatment in de novo PD patients warrants reexamination. Specific questions include: 1) does selegiline offer neuroprotection; 2) what is the best agent with which to initiate symptomatic treatment in de novo PD; and 3) is there a benefit of sustained release levodopa over immediate-release levodopa? Using evidence-based principles, a literature review using MEDLINE, EMBASE, and the Cochrane Library was performed to identify all human trials in de novo PD between 1966 and 1999. Only articles that fulfilled class I or class II evidence were included. Based on this review, the authors conclude: 1) Selegiline has very mild symptomatic benefit (level A, class II evidence) with no evidence for neuroprotective benefit (level U, class II evidence). 2) For PD patients requiring initiation of symptomatic therapy, either levodopa or a DA can be used (level A, class I and class II evidence). Levodopa provides superior motor benefit but is associated with a higher risk of dyskinesia. 3) No evidence was found that initiating treatment with sustained release levodopa provides an advantage over immediate-release levodopa (level B, class II evidence). PMID- 11781400 TI - Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. AB - OBJECTIVE: To survey brain death criteria throughout the world. BACKGROUND: The clinical diagnosis of brain death allows organ donation or withdrawal of support. Declaration of brain death follows a certain set of examinations. The code of practice throughout the world has not been systematically investigated. METHODS: Brain death guidelines in adults in 80 countries were obtained through review of literature and legal standards and personal contacts with physicians. RESULTS: Legal standards on organ transplantation were present in 55 of 80 countries (69%). Practice guidelines for brain death for adults were present in 70 of 80 countries (88%). More than one physician was required to declare brain death in half of the practice guidelines. Countries with guidelines all specifically specified exclusion of confounders, irreversible coma, absent motor response, and absent brainstem reflexes. Apnea testing, using a PCO(2) target, was recommended in 59% of the surveyed countries. Differences were also found in time of observation and required expertise of examining physicians. Additional provisions existed when brain death was due to anoxia. Confirmatory laboratory testing was mandatory in 28 of 70 practice guidelines (40%). CONCLUSION: There is uniform agreement on the neurologic examination with exception of the apnea test. However, this survey found other major differences in the procedures for diagnosing brain death in adults. Standardization should be considered. PMID- 11781401 TI - Manometry combined with cervical puncture in idiopathic intracranial hypertension. AB - OBJECTIVE: To determine by cerebral venography and manometry in patients with idiopathic intracranial hypertension the cause of the previously demonstrated venous hypertension in the superior sagittal and proximal transverse sinuses. METHODS: Cerebral venous sinus pressure was measured before and immediately after C1-2 puncture with removal of 20 to 25 mL of CSF. RESULTS: Lowering the intracranial pressure by lateral C1-2 puncture during manometry has shown that the venous hypertension resolves immediately. CONCLUSION: These studies indicate that the venous hypertension is due to compression of the transverse sinuses by raised intracranial pressure and not due to a primary obstructive process in the cerebral venous sinuses. PMID- 11781402 TI - A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS. AB - OBJECTIVE: To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study. BACKGROUND: It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS. METHODS: Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints. RESULTS: The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group. CONCLUSIONS: Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2 year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity. PMID- 11781403 TI - Prevalence, expenditures, utilization, and payment for persons with MS in insured populations. AB - OBJECTIVE: To determine the prevalence, expenditures, and utilization of enrollees with MS relative to all enrollees in privately insured, Medicare, and Medicaid populations. METHODS: The authors used insurer administrative billing data to identify persons with MS, their insured medical expenditures and utilization, and benchmark general insured population expenditures and utilization. Three samples of insurer billing data were analyzed: nationally representative samples for the privately insured (1994 through 1995) and Medicare (1996 though 1997) populations, and Medicaid data for disabled (1991 through 1996) populations from six states. RESULTS: Using 2 years of diagnoses on claims, the prevalence of MS in the privately insured population was 24 per 10,000, 36 per 10,000 in the Medicare population, and 71 per 10,000 in the Medicaid disabled population. Annual insured expenditures were $7,677 per privately insured enrollee with MS vs $2,394 for all privately insured enrollees, $13,048 per Medicare beneficiary with MS compared with $6,006 for all Medicare beneficiaries, and $7,352 per Medicaid disabled recipient with MS vs $4,088 per disabled recipient without MS. Home health expenditures were very high for Medicare beneficiaries with MS and nursing facility expenditures were very high for Medicaid disabled recipients with MS. A small proportion of enrollees with MS accounted for most expenditures. CONCLUSIONS: Insured enrollees with MS are two to three times more expensive than average insured enrollees. If the premiums that employers or governments pay health insurers and the capitation amounts that insurers pay health care providers do not account for these higher costs, a disincentive is created for the enrollment and care of persons with MS. PMID- 11781404 TI - Familial lipodystrophy associated with neurodegeneration and congenital cataracts. AB - BACKGROUND: The lipodystrophies are characterized by loss of body fat and metabolic disturbances, but the CNS is seldom affected. METHODS: An investigation of a family with partial lipodystrophy and neurologic abnormalities included lipid analysis, dual-energy x-ray absorbtiometry (DEXA) for adiposity, insulin resistance, karyotype and other genetic analyses, peroxisomal function, glycosylation pattern of transferrin and thyroglobulin, and muscle biopsy. RESULTS: The propositus, a 28-year-old woman with congenital partial lipodystrophy and cataracts, presented with a spastic-ataxic gait and lower extremity paresthesiae at age 18. Laboratory investigation revealed a type V hyperlipidemia pattern, insulin resistance, and high alpha-tocopherol levels. A similar syndrome in other family members suggested an autosomal dominant pattern of inheritance. DISCUSSION: The progressive neurologic degenerative condition associated with this autosomal dominant, partial lipodystrophy may be misdiagnosed as MS or spinocerebellar degeneration. Search for a few relevant candidate genes was unrevealing. A genome-wide search to determine the molecular etiology can be undertaken if other similar cases are identified. PMID- 11781405 TI - Older people with impaired mobility have specific loci of periventricular abnormality on MRI. AB - BACKGROUND: Recent investigations using MRI suggest that older persons with mobility impairment have a greater volume of abnormal cerebral white matter compared with persons with normal mobility, thus raising the possibility that those with impairment have lesions in areas critical for the control of mobility. OBJECTIVE: To utilize automated image analysis methods to localize the specific regions of abnormal white matter that distinguish subjects with lower mobility from subjects with higher mobility. METHODS: Tissue classification was performed on subjects' dual-echo long repetition time spin-echo MRI using computer algorithms operating on intensity criteria integrated with anatomic information. Statistical analysis of group differences was obtained after spatially normalizing each brain to a standard reference brain. RESULTS: Four discrete periventricular regions, including bilaterally symmetric frontal and bilateral occipitoparietal regions, were identified as being sensitive (frontal) or specific (occipitoparietal) in discriminating the subjects with lower mobility from subjects with higher mobility. The symmetry of these lesions in individual subjects suggested pathology other than arteriolar infarction. CONCLUSIONS: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging. PMID- 11781406 TI - Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia. AB - OBJECTIVE: To compare the rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (VaD) (n = 79), AD (n = 113), or stroke without dementia (SWD) (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations. METHODS: Study patients were diagnosed using established criteria for dementia and were administered cognitive screening, functional screening, and neuropsychological measures. Baseline dementia severity was rated using the Clinical Dementia Rating Scale. Random effects modeling was used to examine rates of decline and to compare the rates of decline in the three groups. RESULTS: Both patients with VaD and those with AD showed significant cognitive and functional decline during follow-up; patients with VaD declined at a slower rate than patients with AD; and patients diagnosed with SWD at baseline did not show cognitive or functional decline during follow-up. CONCLUSIONS: Patients with VaD decline at a slower rate than patients with AD. Patients who do not meet criteria for dementia soon after stroke may not be at high risk for developing dementia. Future studies are needed to follow VaD patients with longitudinal, specialized MR protocols, concurrent neuropsychological examinations, and neuropathologic examination to determine possible neuroimaging predictors of progressive cognitive and functional decline and to assess the contribution of Alzheimer's pathology to decline in patients diagnosed with VaD. PMID- 11781407 TI - Alzheimer's disease and related dementias increase costs of comorbidities in managed Medicare. AB - OBJECTIVES: To analyze the relationship between comorbid conditions and costs for patients with AD and related dementias (ADRD) in a Medicare managed care organization (MCO). To derive implications for improving management of patients with ADRD. METHODS: Retrospective analysis was carried out on administrative data for 3,934 patients with ADRD and 19,300 age/sex-matched control subjects enrolled in a large Medicare MCO. Patients with ADRD were identified from diagnoses on medical claims and encounter data for a 2-year period. Control subjects were selected from health plan members without dementia. Comorbid conditions were based on the diagnostic classifications from the Charlson comorbidity index. Health care costs and utilization for MCO-covered services for cases were compared with those of control subjects. RESULTS: Prevalence of ADRD was 4.4%, substantially higher than reported in previous studies of Medicare managed care and similar to population-based estimates. After controlling for comorbid conditions, age, and sex, annual costs were $4,134 higher for ADRD patients, resulting in excess costs of $16 million to the MCO. For the 10 most prevalent comorbidities in ADRD patients, adjusted costs were higher for ADRD patients compared with control subjects with the same condition. Higher costs were attributable to higher inpatient and skilled nursing facility utilization. CONCLUSIONS: In this study, prevalence rates for ADRD mirrored population estimates. Costs for patients with ADRD in this Medicare MCO varied considerably by comorbid condition and were substantially higher for patients with both AD and comorbid diseases commonly targeted for disease management, indicating that AD increases costs through effects on the management of comorbid illnesses. These findings indicate that better treatment and care management of AD could reduce the costs of comorbid illnesses commonly experienced by the frail elderly. PMID- 11781408 TI - Lesions of the fusiform face area impair perception of facial configuration in prosopagnosia. AB - BACKGROUND: Prosopagnosia, the inability to recognize faces, is associated with medial occipitotemporal lesions, especially on the right. Functional imaging has revealed a focal region in the right fusiform gyrus activated specifically during face perception. OBJECTIVE: The study attempted to determine whether lesions of this region were associated with defects in face perception in patients with prosopagnosia. METHODS: Five patients with acquired prosopagnosia were tested. They were asked to discriminate faces in which the spatial configuration of features had been altered. This was contrasted with their discrimination of changes in feature color, an alteration that does not affect spatial relations. RESULTS: All four patients whose lesions included the right fusiform face area were severely impaired in discriminating changes in the spatial position of features. The one patient with anterior bilateral lesions was normal in this perceptual ability. For three of the five patients, accuracy was normal for changes in eye color. When subjects knew that only changes in mouth position would be shown, performance improved markedly in two of the four patients who were impaired in the initial test. CONCLUSION: Perception of facial configuration is impaired in patients with prosopagnosia whose lesions involve the right fusiform gyrus. This deficit is especially manifest when attention must be distributed across numerous facial elements. It does not occur with more anterior bilateral temporal lesions. Loss of this ability may contribute to the recognition defect in some forms of prosopagnosia. PMID- 11781409 TI - Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study. AB - OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease. PMID- 11781410 TI - Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. AB - OBJECTIVE: Based on previous findings implicating abnormalities of cortico striatal-thalamo-cortical circuitry in Tourette syndrome (TS), the authors performed a volumetric analysis of frontal and nonfrontal tissue (gray + white matter) in boys with TS, with and without attention deficit hyperactivity disorder (ADHD). METHODS: Frontal and nonfrontal gray and white matter compartment volumes, obtained by a MRI protocol, were analyzed with a 2 x 2 factorial multivariate analysis of variance approach for associations with a TS or ADHD factor in 11 boys with TS only, 14 with TS + ADHD, 12 with ADHD only, and 26 healthy boys. RESULTS: In subjects with TS, the right frontal lobe showed a larger proportion of white matter. In addition, results were consistent with previous reports of reduced frontal lobe volumes associated with ADHD. Our analyses suggested these reductions to be mainly the consequence of smaller gray matter volumes, particularly on the left. CONCLUSIONS: These findings, suggesting the volumetric composition of frontal lobe tissue to be different in TS, support the hypothesis proposing frontostriatal pathway involvement in the pathophysiology of the disorder. Differences in composition of right frontal lobe attributable to white matter do not definitively implicate the hypothesized fiber pathways; however, considered in the context of the unilateral directionality of frontal-striatal circuitry, these results suggest the white matter connections as one explanation for basal ganglia anomalies (loss of normal left > right asymmetry) in TS. PMID- 11781411 TI - Clinical features and changing patterns of neurodegenerative disorders on Guam, 1997-2000. AB - BACKGROUND: In the 1950s, high-incidence ALS and Parkinson-dementia complex (PDC) were identified among Chamorros, the native inhabitants of Guam. Brains of patients with these syndromes showed widespread neurofibrillary tangles. Although ALS and PDC were reported to have dramatically declined in the 1980s, new cases are still encountered. Late-life dementia has received little study among Chamorros. METHODS: From 1997 to 2000, the authors evaluated newly referred and previously identified patients. They screened first-degree relatives of previous registries, and subjects aged 60 or older. Subjects who scored below a cognitive test cutoff or had symptoms or signs consistent with parkinsonism or ALS underwent psychometric testing, assessment by a neurologist, and laboratory studies as appropriate. Consensus diagnoses were made. RESULTS: The authors identified 194 Chamorros with ALS (n = 10), PD (n = 11), PDC (n = 90), or late life dementia (n = 83). Mean ages at onset were 55 for ALS, 68 for PDC, 63 for PD, and 74 for dementia. Late-life dementia was more common in women, and met criteria for probable or possible AD. The APOE-epsilon 4 allele frequency was uniformly low regardless of neurologic diagnosis. CONCLUSIONS: The rapid decline of high-incidence ALS on Guam over the past 40 years suggests the contribution of a modifiable environmental factor. PDC remains relatively common, with an unchanged clinical picture apart from later age at onset. Dementia among elderly Chamorros (termed "Mariana dementia") resembles AD. Autopsy studies will clarify whether this dementia is related to AD pathology or represents a late-life neurofibrillary tangle syndrome more closely allied to PDC. PMID- 11781412 TI - Complications of invasive video-EEG monitoring with subdural grid electrodes. AB - OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate. PMID- 11781413 TI - Age of meningitis or encephalitis is independently predictive of outcome from anterior temporal lobectomy. AB - BACKGROUND: The occurrence of meningitis or encephalitis in early childhood, i.e., < or =4 years of age, may be associated with both the development of medial temporal lobe epilepsy (MTLE) and an excellent operative outcome following an anterior temporal lobectomy (ATL). However, whether the predictive value of this risk factor for partial epilepsy is independent of the finding of mesial temporal sclerosis (MTS) on MRI is not known. METHODS: Consecutive patients (n = 39) with a remote history of meningitis or encephalitis who underwent an ATL were compared with 78 sex- and age-matched control subjects who had not experienced a CNS infection before ATL. All patients in both groups had nonlesional temporal lobe epilepsy and were followed up for at least 12 months postoperatively. RESULTS: There was a trend for the patients with a history of meningitis or encephalitis to have a lower frequency of class I postoperative outcome (61.5% vs 73.1%, p = 0.21). In the meningitis or encephalitis group, a class I outcome was more frequent in those with a history of meningitis or encephalitis at a young age (<4 years) (19/23 vs 5/16, p = 0.002), those with MTS detected on a preoperative MRI (22/31 vs 2/8, p = 0.04), and those with a history of meningitis (16/21 vs 8/18, p = 0.05). Multivariate logistic regression analysis found that a history of meningitis or encephalitis at a young age (b = 2.0, O.R. = 7.5, p = 0.048) was predictive of a class I outcome independent of the presence of MRI-identified MTS (b = 2.0, O.R. = 7.3, p = 0.07). CONCLUSION: The age of occurrence of a remote history of meningitis or encephalitis, but not the type of infection, is predictive of outcome after an ATL independent of the finding of MTS on the preoperative MRI. PMID- 11781414 TI - Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome. AB - BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects. PMID- 11781416 TI - TorsinA immunoreactivity in brains of patients with DYT1 and non-DYT1 dystonia. AB - A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. TorsinA immunohistochemistry was used to examine a case of DYT1, and several cases of non DYT1, dystonia. No evidence was found for alterations of immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA. PMID- 11781415 TI - Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. AB - OBJECTIVE: To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease. BACKGROUND: SN affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy. METHODS: Sixty two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase. RESULTS: IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time. CONCLUSIONS: IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials. PMID- 11781417 TI - A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm. AB - Abnormalities in dopamine neurotransmission are thought to underlie the generation of dystonic movements. The authors performed a case-control allelic association study in patients with the focal dystonia blepharospasm, using polymorphisms in the dopamine receptor and transporter genes. Allele 2 of a DRD5 dinucleotide repeat was significantly associated with blepharospasm. This may indicate a pathogenic role for this receptor. PMID- 11781418 TI - Increased CSF levels of prostaglandin E(2) in variant Creutzfeldt-Jakob disease. AB - The concentration of the cyclooxygenase product prostaglandin E(2) was sixfold higher in CSF samples from 18 cases of variant Creutzfeldt-Jakob disease (CJD) than in a group of eight subjects with other noninflammatory neurologic diseases, and comparable to those found in a group of six patients affected by diseases with a known inflammatory component. This finding suggests that cyclooxygenase activity may have a role in variant CJD pathogenesis, as previously reported in sporadic CJD. PMID- 11781419 TI - Cerebral vasoconstriction and stroke after use of serotonergic drugs. AB - Serotonin (5-hydroxytryptamine) is a potent vasoconstrictor amine. The authors report three patients who developed thunderclap headache, reversible cerebral arterial vasoconstriction, and ischemic strokes (i.e., the Call-Fleming syndrome). The only cause for vasoconstriction was recent exposure to serotonergic drugs in all patients, and to pseudoephedrine in one patient. These cases, and the literature, suggest that the use of serotonin-enhancing drugs can precipitate a cerebrovascular syndrome due to reversible, multifocal arterial narrowing. PMID- 11781420 TI - The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke. AB - The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. Overall, tirilazad had no significant effect on infarct volume. In the subgroups of male patients and of those with a cortical infarct, tirilazad significantly reduced infarct volume. These effects were reduced to nonsignificant trends after adjustment for imbalances in baseline characteristics. In conclusion, early treatment of patients with tirilazad has no effect on infarct volume. PMID- 11781421 TI - Prevalence estimates for MS in the United States and evidence of an increasing trend for women. AB - The purpose of this study was to provide current age-, sex-, and region-specific MS prevalence estimates and to identify trends using the National Health Interview Survey. The overall prevalence estimate was 85/100,000 population, or approximately 211,000 (+/-20,000) persons. A 50% increase was observed in the number of women reporting MS for 1991 through 1994 vs 1982 through 1986. The observed trend in higher numbers of self-reported MS among women is consistent with recent observations of higher prevalence and incidence. PMID- 11781422 TI - Predictors of functional disability and mortality after status epilepticus. AB - The authors identified predictors of functional disability and mortality after status epilepticus in a multivariate analysis of 83 episodes in 74 patients. Twenty-one percent (14/85) of episodes were fatal. Increased age (OR = 1.1; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 6.0; 95% CI, 1.2 to 30.3) were predictors of mortality. Functional outcome at discharge deteriorated in 23% (16/69) of nonfatal episodes. Increased length of hospitalization (OR = 1.04; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 3.9; 95% CI, 1.0 to 14.7) were predictors of functional disability. PMID- 11781424 TI - Meningioma disguised as cerebral hematoma. PMID- 11781423 TI - Plasma exchange for severe attacks of CNS demyelination: predictors of response. AB - The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained. PMID- 11781425 TI - Subtherapeutic free phenytoin levels following fosphenytoin therapy in status epilepticus. PMID- 11781426 TI - Paraneoplastic stiff-person syndrome: no tumor progression over 5 years. PMID- 11781427 TI - Sporadic CJD clinically mimicking variant CJD with bilateral increased signal in the pulvinar. PMID- 11781428 TI - Presentation of myasthenia gravis mimicking blepharospasm. PMID- 11781429 TI - Anti-basal ganglia antibodies are absent in patients with primary blepharospasm. PMID- 11781432 TI - Handicap after acute whiplash injury. PMID- 11781437 TI - An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. PMID- 11781438 TI - Handicap after acute whiplash injury. PMID- 11781439 TI - Recertification for neurologists. PMID- 11781440 TI - Perilymph fistula associated with pulse-synchronous eye oscillations. PMID- 11781441 TI - Treatment of drug-induced psychosis with quetiapine and clozapine in Parkinson's disease. PMID- 11781442 TI - Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. PMID- 11781445 TI - Dicaesium silver zinc thiocyanate, Cs2[AgZn(SCN)5]. AB - The title compound, dicaesium(I)-mu-thiocyanato-kappa2N:S-zinc(II)-tetra-mu thiocyanato-kappa2S:N-argentate(I), crystallizes in the orthorhombic space group Pmn2(1) and contains units of composition AgZn(SCN)3 lying on a mirror plane and bonded together through Cs+ ions and thiocyanate groups. The crystal studied contained equal numbers of inversion twins. PMID- 11781446 TI - Ca3Mn2O7. AB - The tricalcium dimanganese heptaoxide (Ca3Mn2O7) member of the Ruddlesden-Popper series Ca(n+1)Mn(n)O(3n+1), i.e. with n = 2, was previously reported with an I centred tetragonal lattice [a(t) = 3.68 and c(t) = 19.57 A] by Fawcett, Sunstrom, Greenblatt, Croft & Ramanujachary [Chem. Mater. (1998), 10, 3643-3651]. It is now found to be orthorhombic, with an A-centred lattice [a = 5.2347 (6), b = 5.2421 (2) and c = 19.4177 (19) A]. The structure has been refined in space group A2(1)am using X-ray single-crystal diffraction data and assuming the existence of twin domains related by the (1-10) plane. A comparison with the basic perovskite structure CaMnO3 (n = infinity) is proposed. PMID- 11781447 TI - The mixed oxide MoVAlO7. AB - A single crystal of MoVAlO7, vanadium aluminium molybdate, has been grown. The present structure determination is more precise than a previous powder-pattern investigation [Knorr, Jacubus, Dabrowska & Kurzawa (1998). Eur. J. Solid State Inorg. Chem. 35, 519-530]. A three-dimensional [MoAlO6](3n-)n network surrounds infinite strings of [VO]3+ groups [V-O = 1.586 (4) A] lying in the mirror planes. PMID- 11781448 TI - Synchrotron-radiation study of the two-leg spin-ladder (VO)2P2O7 at 120 K. AB - The crystal structure of the ambient-pressure phase of vanadyl pyrophosphate, (VO)2P2O7, has been precisely determined at 120 K from synchrotron X-ray diffraction data measured on a high-quality single crystal. The structure refinement unambiguously establishes the orthorhombic space group Pca2(1) as the true crystallographic symmetry. Moreover, it improves the accuracy of previously published atomic coordinates by one order of magnitude, and provides reliable anisotropic displacement parameters for all atoms. Along the a axis, the structure consists of infinite two-leg ladders of vanadyl cations, (VO)2+, which are separated by pyrophosphate anions, (P2O7)4-. Parallel to the c axis, the unit cell comprises two alternating crystallographically inequivalent chains of edge sharing VO5 square pyramids bridged by PO4 double tetrahedra. No structural phase transition has been observed in the temperature range between 300 and 120 K. PMID- 11781449 TI - Beta-Sm(OH)2Cl: a new lamellar variety. AB - Crystals of dihydroxysamarium chloride were synthesized hydrothermally at 473 K. The orthorhombic structure was determined by single-crystal X-ray diffraction analysis. Beta-Sm(OH)2Cl exhibits a lamellar structure built up from the stacking of neutral slabs; all the atoms lie on crystallographic mirror planes. The structure is stabilized by strong hydrogen bonds between the OH groups and the Cl ions of adjacent layers. PMID- 11781450 TI - AgCo3PO4(HPO4)2. AB - The structure of the hydrothermally synthesized compound AgCo3PO4(HPO4)2, silver tricobalt phosphate bis(hydrogen phosphate), consists of edge-sharing CoO6 chains linked together by the phosphate groups and hydrogen bonds. The three-dimensional framework delimits two types of tunnels which accommodate Ag+ cations and OH groups. The title compound is isostructural with the compounds AM3H2(XO4)3 (A = Na or Ag, M = Co or Mn, and X = P or As) of the alluaudite structure type. PMID- 11781451 TI - Monoclinic AlPO4 tridymite at 473 and 463 K from X-ray powder data. AB - Upon cooling from its hexagonal high-temperature modification, AlPO4 (aluminium phosphate) tridymite successively transforms to several displacively distorted forms, including a normal structure-incommensurate-lock-in phase transition sequence. The space-group symmetries in this series are P112(1), P112(1)(alphabeta0) and P2(1)2(1)2(1), respectively. The distortion pattern of the intermediate P112(1) phase can be described as alternate shifts of adjacent layers of tetrahedra coupled with tilting of the tetrahedra. The symmetry and direction of the shifts are different from the analogous SiO2 tridymite modification. The atomic displacement parameters of the O atoms are strongly anisotropic due to thermal motions of the rigid tetrahedra. Condensation of a lattice vibration mode results in the formation of an incommensurate structural modulation below 473 K. The 3+1 superspace-group symmetry of the modulated phase is P112(1)(alphabeta0). PMID- 11781452 TI - Calcium dicaesium silver thiocyanate dihydrate. AB - The title compound, CaCs2[Ag2(SCN)6]*2H2O, forms a continuous structure where the Ag atoms form chains with S atoms in the c-axis direction. The chains are bonded together through Cs and Ca atoms. The crystal water of the structure is bonded to the Ca atoms, which lie on centers of symmetry. PMID- 11781453 TI - Hydrogen-bonded adducts of ferrocene-1,1'-diylbis(diphenylmethanol): monomeric and polymeric adducts with 1,2-bis(4-pyridyl)ethene and 1,6-diaminohexane. AB - In the adduct ferrocene-1,1'-diylbis(diphenylmethanol)-1,2-bis(4-pyridyl)ethene (1/1), [Fe(C18H15O)2]*C12H10N2, there is an intramolecular O-H...O hydrogen bond in the ferrocenediol component and a single O-H...N hydrogen bond linking the diol to the diamine, which is disordered over two sets of sites, so forming a finite monomeric adduct. In the adduct ferrocene-1,1'-diylbis(diphenylmethanol) 1,6-diaminohexane (2/1), 2[Fe(C18H15O)2]*C6H16N2, the amine lies across a centre of inversion in space group P-1. There is an intramolecular O-H...O hydrogen bond in the ferrocenediol, and the molecular components are linked by O-H.N and N-H.O hydrogen bonds, one of each type, into a C3(3)(13)[R6(6)(12)] chain of rings. PMID- 11781454 TI - Hydrogen-bonded adducts of ferrocene-1,1'-diylbis(diphenylmethanol): a finite cyclic 1:1 adduct with 2,2'-dipyridylamine. AB - In ferrocene-1,1'-diylbis(diphenylmethanol)-2,2'-dipyridylamine (1/1), [Fe(C18H15O)2]*C10H9N3, (I), there is an intramolecular O-H...O hydrogen bond [H...O 2.03 A, O...O 2.775 (2) A and O-H...O 147 degrees ] in the ferrocenediol component, and the two neutral molecular components are linked by one O-H...N hydrogen bond [H...N 1.96 A, O...N 2.755 (2) A and O-H...N, 157 degrees ] and one N-H...O hydrogen bond [H...O 2.26 A, N.O 3.112 (2) A and N-H...O 164 degrees ] forming a cyclic R3(3)(8) motif. One of the pyridyl N atoms plays no part in the intermolecular hydrogen bonding, but participates in a short intramolecular C H...N contact [H...N 2.31 A, C...N 2.922 (2) A and C-H...N 122 degrees ]. PMID- 11781455 TI - A dinuclear uranium(IV) complex of the chelating ligand 1,2,3,4-tetramethyl-5-(2 pyridyl)cyclopentadiene. AB - The ligand 1,2,3,4-tetramethyl-5-(2-pyridyl)cyclopentadiene (cp*py) forms a dinuclear complex with U(IV), i.e. di-mu-oxo-bis[chloro(diethyl ether kappaO)[(eta5,kappaN)-1,2,3,4-tetramethyl-5-(2 pyridyl)cyclopentadienyl]uranium(IV)], [U2Cl2O2(C14H16N)2(C4H10O)2], in which cp*py acts as a chelating ligand, being bound to the metal atom by the cyclopentadienyl unit and also by the N atom of the pyridyl ring. PMID- 11781456 TI - Bis[2-(pyrazol-3-yl)phenolato-kappa2N2,O]copper(II) dimethanol solvate. AB - The title compound, [Cu(C9H7N2O)2]*2CH3OH, contains a crystallographically centrosymmetric near-regular square planar Cu(II) centre with trans-disposed chelating ligands. The complex molecules associate into a one-dimensional polymeric chain via hydrogen bonding to the solvent molecules. PMID- 11781457 TI - Mu1,3-azido-diazidotetrakis(1,10-phenanthroline)dicopper(II) azide tetrahydrate. AB - In the title compound, [Cu2(mu-(1,3)-N3)(N3)2(phen)4](N3)*4H2O (phen is 1,10 phenanthroline, C12H8N2), each of the two Cu atoms is surrounded by two N atoms of two azide anions and by four N atoms of two 1,10-phenanthroline ligands [Cu-N distances are 1.964 (3), 2.009 (3), 2.018 (3), 2.054 (3), 2.306 (3) and 2.759 (4) A], forming an elongated CuN6 octahedron. An ideally linear mu(1,3)-azide anion bridges two Cu atoms to form a dimeric structure with the central N atom located on a centre of inversion. Moreover, the adjacent dimeric units are connected by hydrogen-bond interactions to produce one-dimensional chains. A two-dimensional supramolecular array is formed by pi-pi interactions between the aromatic rings of 1,10-phenanthroline ligands of adjacent dimeric units. PMID- 11781458 TI - trans-Bis(diethanolamine-N,O)bis(saccharinato-N)cadmium(II). AB - The structure of the title complex consists of isolated [Cd(C7H4NO3S)2(C4H11NO2)2] units. The Cd2+ cation lies on an inversion centre and is octahedrally coordinated by two N,O-bidentate diethanolamine (dea) and two N bonded saccharinate (sac) ligands [saccharin is 1,2-benzisothiazol-3(2H)-one 1,1 dioxide]. The dea ligands constitute the equatorial plane of the octahedron, forming two five-membered chelate rings around the Cd(II) ion, while the sac ligands are localized at the axial positions. The Cd-N(sac), Cd-N(dea) and Cd O(dea) bond distances are 2.3879 (12), 2.3544 (14) and 2.3702 (13) A, respectively. The H atoms of the free and coordinated hydroxyl groups of the dea ligands are involved in hydrogen bonding with the carbonyl and sulfonyl O atoms of the neighbouring sac ions, while the amine H atom forms a hydrogen bond with the free hydroxyl O atom. The individual molecules are held together by strong hydrogen bonds, forming an infinite three-dimensional network. PMID- 11781459 TI - Bis(pyridine-2,6-dimethanol-N,O,O')cobalt(II) and -copper(II) disaccharinate dihydrate: three-dimensional structures with extensive hydrogen bonds and aromatic pi-pi-stacking interactions. AB - Bis(pyridine-2,6-dimethanol-N,O,O')cobalt(II) disaccharinate dihydrate, [Co(C7H9NO2)2](C7H4NO3S)2*2H2O, (I), and bis(pyridine-2,6-dimethanol N,O,O')copper(II) disaccharinate dihydrate, [Cu(C7H9NO2)2](C7H4NO3S)2*2H2O, (II), collectively [M(dmpy)2](sac)2*2H2O (where M is Co(II) or Cu(II), sac is the saccharinate anion and dmpy is pyridine-2,6-dimethanol), are isostructural. The [M(dmpy)2]2+ cations exhibit distorted octahedral geometry in which the two neutral dmpy species act as tripodal N,O,O'-tridentate ligands. The crystal packing is determined by hydrogen bonding, as well as by weak pyridine saccharinate pi-pi-stacking interactions. PMID- 11781460 TI - Sodium p-nitrobenzoxasulfamate monohydrate. AB - The title compound, alternatively named sodium 6-nitro-3H-1,2,3-benzoxathiazole 2,2-dioxide monohydrate, Na+*C6H3N2O5S-*H2O, consists of chains of NaO7 units, with the seven donor-O atoms coming from two water molecules and five p nitrobenzoxasulfamate anions. The seven-coordinate geometry around the Na+ ion is described as monocapped trigonal prismatic, but with a large distortion from ideal geometry. Each triangular face is defined by one O atom each from a water molecule, a nitro group and a sulfonyl group. An O atom from a sulfonyl group caps one of the square faces of the trigonal prism in an unsymmetrical fashion. The water molecules and one sulfonyl O atom are involved in bridging adjacent units, as is the nitro group of the anion. The sulfamate ions adopt an antiparallel alignment between the NaO7 units and are connected to each other by C-H...O and pi-pi interactions. The three-dimensional crystal structure is stabilized by a network of strong O-H...N hydrogen bonds. PMID- 11781461 TI - Tetrakis[phthalocyaninato(2-)antimony(III)] hexadecaiodotetraantimony(III). AB - Crystals of a new antimony(III) phthalocyanine complex with the formula [Sb(C32H16N8)]4(Sb4I16), or (SbPc)4+*[Sb(4)I(16)]4-, where Pc is phthalocyaninate, have been obtained by the reaction of pure powdered antimony with phthalonitrile under a stream of iodine vapour. The crystals are built up from separate but interacting (SbPc)+ cations and centrosymmetric [Sb4I16]4- anions. Each Sb atom of two independent (SbPc)+ units is bonded to the four isoindole N atoms of the phthalocyaninate(2-) macrocycle and lies 1.0 A out of the plane defined by four isoindole N atoms. The anionic part of the complex consists of four SbI6 distorted octahedra joined together into a centrosymmetric [Sb4I16]4- anion. The arrangement of oppositely charged moieties in the crystal is mainly determined by ionic attraction and by a set of distinct donor-acceptor interactions between (SbPc)+ and [Sb4I16]4- ions. PMID- 11781462 TI - Two orthopalladated chromophores. AB - The title compounds, [5-(dimethylamino)-2-[N-(4 methoxyphenyl)iminomethyl]phenyl][N-(4-methoxyphenyl)-4 nitrosalicylaldiminato]palladium(II), [Pd(C14H11N2O4)(C16H17N2O)], (I), and [4 (diethylamino)-N-(4-methoxyphenyl)salicylaldiminato][2-[N-(4 methoxyphenyl)iminomethyl]-5-nitrophenyl]palladium(II) dichloromethane hemisolvate, [Pd(C14H11N2O3)(C18H21N2O2)]*0.5CH2Cl2, (II), both contain push-pull chromophores coordinated to Pd in a square-planar arrangement. In both compounds, the five-membered orthopalladated ring is essentially planar, while the coordinated six-membered ring is not. Deviations from a coplanar arrangement of the phenylene rings of the coordinated Schiff bases are observed in both (I) and (II) as a result of intramolecular steric interactions. PMID- 11781463 TI - Hexa-mu-chloro-mu4-oxo-tetrakis[(4,5-dihydro-2-methyl-1,2-thiazole kappaN)copper(II)]. AB - The title compound, [Cu4Cl6O(C4H7NS)4], was obtained by the reaction of CuCl2*2H2O with 2-methyl-2-thiazoline in methanol. The complex has twofold crystallographic symmetry and contains a tetrahedron of four Cu(II) atoms coordinating a central mu4-O atom, with the six edges of the tetrahedron bridged by Cl atoms. Distance ranges are Cu-O 1.917 (4)-1.920 (4) and Cu-Cl 2.370 (2) 2.445 (2) A. PMID- 11781464 TI - Diacetatobis(trimethylenethiourea)zinc(II) monohydrate. AB - In the title compound, [Zn(CH3COO)2(C4H8N2S)2]*H2O, the Zn atom is tetrahedrally coordinated in the ZnO2S2 form. N-H...O and O-H...O intramolecular and intermolecular hydrogen bonds are formed by the four N atoms and the water molecule. N-H...O intermolecular hydrogen bonds and C-H...S and C-H...O intermolecular interactions interconnect columns formed by the molecules into layers. Adjacent layers are then linked by other N-H...O and O-H...O intermolecular hydrogen bonds to form a three-dimensional framework throughout the structure. The orientations of the acetate planes are such that the Zn atom lies within them. PMID- 11781465 TI - Aqua(nitrilotriacetato)(1,10-phenanthroline)iron(III) monohydrate: a seven coordinate iron(III) complex. AB - Reaction of 1,10-phenanthroline (phen) with iron trichloride in the presence of sodium nitrilotriacetate (NTA) resulted in the formation of red crystals of the title complex, [Fe(C6H6NO6)(C12H8N2)(H2O)]*H2O. The Fe atom has a distorted capped trigonal prismatic coordination comprised of one tetradentate NTA, one bidentate phen molecule and a water molecule. Intermolecular O-H...O hydrogen bonds link the molecules into infinite chains. The chains are crosslinked by hydrogen bonds involving the solvent water molecule, leading to an infinite ladder packing mode. PMID- 11781466 TI - Poly[[[tri(urea-kappaO)manganese(II)]-mu-thiocyanato-kappa2N:S-mercury(II)]-tri mu-tetrathiocyanato]. AB - The title complex, [MnHg(SCN)4(CH4N2O)3]n, consists of slightly distorted octahedral MnN3O3 and tetrahedral HgS4 units. The Mn(II) atom is coordinated by the O atoms of three urea molecules and by the N atoms of three SCN- ions; Hg(II) is coordinated by four S atoms from SCN- ions. Each pair of Mn(II) and Hg(II) atoms is connected by an -SCN- bridge, forming infinite two-dimensional -Mn-NCS Hg- networks. PMID- 11781467 TI - Aquabromo(6-carboxypyridine-2-carboxylato-O,N,O')mercury(II). AB - The title compound, [HgBr(C7H4NO4)(H2O)], was obtained by the reaction of an aqueous solution of mercury(II) bromide and pyridine-2,6-dicarboxylic acid (picolinic acid, dipicH(2)). The shortest bond distances to Hg are Hg-Br 2.412 (1) A and Hg-N 2.208 (5) A; the corresponding N-Hg-Br angle of 169.6 (1) degrees corresponds to a slightly distorted linear coordination. There are also four longer Hg-O interactions, three from dipicH(-) [2.425 (4) and 2.599 (4) A within the asymmetric unit, and 2.837 (4) A from a symmetry-related molecule] and one from the bonded water molecule [2.634 (4) A]. The effective coordination of Hg can thus be described as 2+4. The molecules are connected to form double-layer chains parallel to the y axis by strong O-H.O hydrogen bonds between carboxylic acid groups of neighbouring molecules, and by weaker hydrogen bonds involving both H atoms of the water molecule and the O atoms of the carboxylic acid groups. PMID- 11781468 TI - A dimeric constrained-geometry titanium complex linked by double Ti-CH2-Al-CH2 heterocycles. AB - In the structure of bis([N-[dimethyl(1eta5-2,3,4,6 tetramethylindenyl)silyl]cyclohexylamido-1kappaN](methyl-3kappaC)-di-mu3 methylene-1:2:3kappa3C;1:3:3'kappa3C-tris(pentafluorophenyl-2kappaC)titanium) benzene disolvate, [Me2Si(eta5-2,3,4,6-Me4C9H2)(C6H11N)]Ti[(mu3 CH2)Al(C6F5)3][AlMe(mu3-CH2)]2 or [Ti2(C21H7AlF15)2(C21H31NSi)2].2C6D6, the dimer is located on an inversion center, and the two Ti centers are linked by double Ti(mu3-CH2)Al(C6F5)3AlMe(mu3-CH2) heterocycles. The electron-deficient Ti centers are further stabilized by two alpha-agostic interactions between Ti and one H atom of each bridging methylene group. PMID- 11781469 TI - N-(ferrocenecarbonyl)-N'-(quinolin-8-yl)thiourea. AB - In the title compound, [Fe(C5H5)(C16H12N3OS)], the 8-aminoquinoline and acylthiourea moieties are almost planar. There are two perpendicular arrangements of the molecules in the crystal with slightly different conformations. The two cyclopentadienyl rings in each molecule are parallel and eclipsed. PMID- 11781470 TI - Barium(II)-2,4-dinitrophenolate-18-crown-6 at 183 K. AB - The title compound, bis(2,4-dinitrophenolato-kappa2O,O')(1,4,7,10,13,16 hexaoxadecane-kappa6O)barium(II), [Ba(C6H3N2O5)2(C12H24O6)], is a 1:1 complex of barium(II)-2,4-dinitrophenolate and 1,4,7,10,13,16-hexaoxacyclooctadecane (18 crown-6). Its structure is located on a crystallographic inversion centre. The temperature dependence of the crystal structure has been studied. The monoclinic beta angle of the P2(1)/n space group increases with increasing temperature. The packing structure of the complex is stabilized by intermolecular C-H...O interactions. PMID- 11781471 TI - trans-bis(benzoato-O)tetrakis(methanol-O)iron(II): ligand bulk is not structure determining. AB - The title compound, [Fe(C7H5O2)2(CH4O)4], is a centrosymmetric six-coordinate Fe(II) complex coordinated by two axial monodentate benzoate ligands and four methanol ligands in the equatorial plane [Fe-O(benzoate) 2.0935 (7) A, and Fe O(methanol) 2.1310 (7) and 2.1290 (7) A]. The benzoate ligands adopt monodentate ligation, rather than a bridged polymeric structure, because of strong intra- and intermolecular hydrogen bonds to the methanol ligands. This structure is nearly identical to that obtained with a much bulkier carboxylate ligand [Chavez, Que & Tolman (2001). Chem. Commun. pp. 111-112]. PMID- 11781472 TI - A triboluminescent europium(III) complex. AB - The crystal structure of (4,4'-dimethyl-2,2'-bipyridyl)tris[3,3,3-trifluoro-1-(2 thenoyl)propan-2-onato]europium(III), or more commonly (4,4'-dimethyl-2,2' bipyridyl)tris(2-thenoyltrifluoroacetonato)europium(III), [Eu(C8H4F3O2S)3(C12H12N2)], has been determined. Crystals of the complex emit vivid red light when scratched or fractured. This triboluminescent activity seems to correlate with the non-centrosymmetric crystal structure and disorder of the thienyl rings and CF3 groups which is present here and in similar compounds. While modeling the thienyl-ring disorder, it was noted that the bond angle at the C atom replaced by S is a sensitive sign of even small rotational ring disorder. The coordination geometry of the Eu(III) ion can be described as square antiprismatic, with coordination by the six O atoms of the three chelating beta diketonate ligands and the two N atoms of the neutral bipyridyl ligand. PMID- 11781473 TI - A second polymorph of 1,1,4,4-tetramethylpiperazinium pentabromothallate(III). AB - A new polymorph of the title compound, (C8H20N2)[TlBr5], contains cations located about crystallographic centres of inversion and trigonal-bipyramidal anions which have a C2 axis passing through the equatorial plane of the anion. The anion has the least distorted geometry seen so far in any structure possessing this anion and the axial Tl-Br bonds are about 0.13 A longer than the equatorial Tl-Br bonds, consistent with related structures. The anion in the initially reported polymorph has lower symmetry and a greater distortion of the trigonal-bipyramidal coordination. PMID- 11781474 TI - trans-diacetonitrilebis(di-2-pyridyl sulfide-N,N')ruthenium(II) bis(tetrafluoroborate) monohydrate. AB - The title complex, [Ru(C10H8N2S)2(CH3CN)2](BF4)2*H2O, is the product of the solvolysis of [Ru(dps-N,N)2(dps-N,S)](PF(6))2 (dps is di-2-pyridyl sulfide) in the presence of HBF4 in acetone-acetonitrile at room temperature. There are two independent cations, with the Ru atoms on inversion centres; each Ru atom has an octahedral geometry with the dps molecules behaving as N,N'-bidentate ligands and assuming a trans arrangement. PMID- 11781475 TI - Di-mu-chloro-bis([2-[N,N-bis(2-aminoethyl)amino-kappa3N]ethylaminium]-copper(II)) bis(naphthalene-1,5-disulfonate) pentahydrate. AB - The title compound, [Cu2(C6H19N4)2Cl2](C10H6O6S2)2*5H2O, is comprised of discrete [Cu2(tren)2Cl2]2+ dimers [tren is 2-[N,N-bis(2-aminoethyl)amino]ethylaminium] and naphthalene-1,5-disulfonate anions. Two Cl- anions bridge two Cu(II) ions, each of which is also coordinated by two of the primary and the tertiary amino N atoms of the tren ligand, giving each metal atom a distorted square-pyramidal coordination geometry. The cation lies about an inversion centre and the asymmetric unit also has two independent anions lying about inversion centres. PMID- 11781477 TI - Adducts of 1,1,1-tris(4-hydroxyphenyl)ethane with 1,2-bis(4-pyridyl)ethane and 1,2-bis(4-pyridyl)ethene: continuously interwoven structures in three dimensions. AB - In the adduct 1,2-bis(4-pyridyl)ethane-1,1,1-tris(4-hydroxyphenyl)ethane (1/2), C12H12)2*2C20H18O3, the bipyridyl component lies across an inversion centre in P 1. The tris-phenol molecules [systematic name: 4,4',4"-(ethane-1,1,1 triyl)triphenol] are linked by O-H...O hydrogen bonds to form sheets built from R4(4)(38) rings, and symmetry-related pairs of sheets are linked by the bipyridyl molecules via O-H...N hydrogen bonds to form open bilayers. Each bilayer is interwoven with two adjacent bilayers, forming a continuous three-dimensional structure. In the adduct 1,2-bis(4-pyridyl)ethene-1,1,1-tris(4 hydroxyphenyl)ethane-methanol (1/1/1), C12H10N2*C20H18O3*CH4O, the molecules are linked by O-H...O and O-H...N hydrogen bonds into three interwoven three dimensional frameworks, generated by single spiral chains along [010] and [001] and a triple-helical spiral along [100]. PMID- 11781476 TI - catena-poly[[[[N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2 yl)glycinato-O]pentaaquastrontium]-mu-N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4 oxopyrimidin-2-yl)glycinato-O:O'] monohydrate]: coordination polymer chains linked by hydrogen bonds into a three-dimensional framework. AB - In the title compound, [Sr(C7H8N5O4)2(H2O)5]*H2O, one of the anionic (C7H8N5O4)- ligands acts as a simple monodentate ligand coordinated via a carboxyl O atom, while the other acts as a bridging ligand between pairs of Sr atoms, utilizing one carboxyl O and the nitroso O atom, so generating a one-dimensional coordination polymer. Five water molecules are coordinated to Sr, resulting in eight-coordination in the form of a distorted square antiprism, while the sixth water molecule is hydrogen bonded to a coordinated water. The coordination polymer chains are reinforced by O-H.N and O-H...O hydrogen bonds and are linked into a three-dimensional framework by an extensive series of N-H...O and O-H...O hydrogen bonds. PMID- 11781479 TI - Phthalimide at 120 K: perforated molecular ribbons containing three different ring motifs. AB - Molecules of phthalimide [1H-isoindole-1,3(2H)-dione], C8H5NO2, are linked by N H...O hydrogen bonds [H...O 2.02 A, N...O 2.8781 (16) A and N-H...O 167 degrees ] and by C-H...O hydrogen bonds [H...O 2.54 and 2.56 A, C...O 3.3874 (18) and 3.4628 (19) A, and C-H...O 149 and 159 degrees ] into molecular ribbons, which are pierced by three different ring motifs; there are two centrosymmetric R2(2)(8) rings, each containing a single hydrogen bond, N-H...O in one case and C H...O in the other, and R2(2)(9) rings containing all three hydrogen bonds. PMID- 11781478 TI - A structural hierarchy in the hydrogen-bonded adduct N,N'-dimethylpiperazine tartaric acid-water (1/2/2): an N-component N-dimensional structure (N =3) with substructures having N = 1 and 2. AB - In the hydrated adduct N,N'-dimethylpiperazine-1,4-diium bis(3-carboxy-2,3 dihydroxypropanoate) dihydrate, [MeNH(CH2CH2)2NHMe]2+*2(C4H5O6)-*2H2O or C6H16N2(2+)*2C4H5O6-*2H2O, formed between racemic tartaric acid and N,N' dimethylpiperazine (triclinic P-1, Z' = 0.5), the cations lie across centres of inversion. The anions alone form chains, and anions and water molecules together form sheets; the sheets are linked by the cations to form a pillared-layer framework. The supramolecular architecture thus takes the form of a family of N dimensional N-component structures having N = 1, 2 or 3. PMID- 11781480 TI - A novel binucleating macrocyclic ligand with two alcohol pendants. AB - A novel binucleating 24-membered macrocyclic ligand, 6,20-bis(2-hydroxyethyl) 3,6,9,17,20,23-hexazatricyclo[23.3.1.1(11,15)]triaconta-1(29),11(30),12,14,25,27 hexaene (L), was synthesized and crystallized as the tetrahydrobromide salt, i.e. 6,20-bis(2-hydroxyethyl)-6,20-diaza-3,9,17,23 hexaazoniatricyclo[23.3.1.1(11,15)]triaconta-1(29),11(30),12,14,25,27-hexaene tetrabromide tetrahydrate, C28H50N6O2(4+)*4Br(-)*4H2O. A crystallographic inversion center is located in the macrocyclic cavity and the two hydroxyethyl pendants are on opposite sides of the macrocyclic plane. The benzene rings of the macrocycle are parallel to each other and a pi-pi-stacking interaction exists between the benzene rings of adjacent macrocycles, which are separated by 3.791 (9) A. An infinite intermolecular hydrogen-bond network stabilizes the crystal. PMID- 11781481 TI - Bis[2-(2-hydroxyphenoxy)ethyl] ether methanol solvate. AB - The title compound, 2,2'-(3-oxapentane-1,5-diyldioxy)diphenol, crystallizes as a methanol solvate, C16H18O5*CH4O. The methanol molecule, roughly perpendicular to the mean plane of the polyether molecule, is hydrogen bonded to the two polyether OH groups and to the central ether O atom. Possible C-H...pi intermolecular interactions are present. PMID- 11781482 TI - An anthracene dimer with a fused 1,3-dithiole ring at 193 K. AB - The first butterfly-shaped anthracene dimer including S atoms,8,9-dihydro 3a,8[1',2']:9,13b[1",2"]dibenzenodibenzo[3,4:7,8]cycloocta[1,2-d]-1,3-dithiole, C29H20S2, contains an exceptionally long Csp3-Csp3 bond of 1.672 (2) A in the fused 1,3-dithiole ring. The length of the other bond bridging the anthracene moieties is 1.604 (3) A. PMID- 11781483 TI - Powder diffraction study of the hydrogen bonds in nitroxoline and its hydrochloride. AB - The crystal structures of 8-hydroxy-5-nitroquinoline, C9H6N2O3, (I), and 8 hydroxy-5-nitroquinolinium chloride, C9H7N2O3+*Cl-, (II), have been determined from X-ray powder data. In (I), the molecules are linked via moderately strong hydrogen bonds to form dimers. Such a packing motif is likely to be responsible for the low solubility of (I) in water. In (II), the inversion-related cations form stacks, and anions fill the interstack channels. PMID- 11781484 TI - (+)-3-oxo-4-pregnene-20beta-carboxylic acid: catemeric hydrogen bonding in a steroidal keto acid. AB - The title keto acid, (+)-23,24-dinor-3-oxochol-4-en-22-oic acid, C(22)H(32)O(3), forms carboxyl-to-ketone hydrogen-bonding catemers [O...O = 2.699 (4) A and O H...O = 173 degrees ], linking molecules screw-related in b. The four molecules in the cell form two parallel counter-directional chains, screw-related in a. Intermolecular C-H...O=C close contacts to different neighboring molecules were found for the ketone and the acid. PMID- 11781485 TI - 1,1'-diacetyl-3-hydroxy-2,2',3,3'-tetrahydro-3,3'-bi(1H-indole)-2,2'-dione. AB - In the title compound, C20H16N2O5, both of the 1-acetylisatin (1-acetyl-1H-indole 2,3-dione) moieties are planar and form a dihedral angle of 74.1 (1) degrees. Weak intermolecular hydrogen bonds and C-H...pi interactions stabilize the packing in the crystal. PMID- 11781486 TI - 4-[3-(3,4-dimethoxyphenyl)prop-2-enoyl]phenyl methacrylate and 4-[3-(2 bromophenyl)prop-2-enoyl]phenyl methacrylate. AB - Chalcones (alpha,beta-unsaturated ketones) are effective antitumour agents. It has been proved that having halogen or methoxy groups substituted in various positions of the phenyl ring enhances the activity of chalcones many times. The title compounds, C21H20O5 and C19H15BrO3, respectively, were chosen for crystallographic study in order to determine their structures and conformations. In both compounds, the keto group is in the s-cis conformation and is almost planar. There are weak intramolecular interactions in both structures. PMID- 11781487 TI - 2,4-dihydroxy-1,3-bis(methoxycarbonylmethoxy)calix[4]arene and 1,3 bis(ethoxycarbonylmethoxy)-2,4-dihydroxycalix[4]arene chloroform solvate. AB - The two title calix[4]arene compounds, C34H32O8, (I), and C36H36O8*CH3Cl, (II), respectively, which differ only in the size of the alkyl function on the pendant ester group, are compared. Compound (I) forms a novel supramolecular array, whilst (II) fails to do so due to accommodating a chloroform guest molecule in the lower-rim cavity. PMID- 11781488 TI - Azinyl sulfides. LXVII. 1-methylpyridine-4(1H)-thione. AB - The title compound, C6H7NS, is planar, with endo-C-N-C bond angles of 118.7 (2) degrees and 118.8 (2) degrees, and C-S bond lengths of 1.697 (2) and 1.692 (2) A for the two symmetrically independent molecules. 1-methylpyridinium-4-thiolate is the major contributor to the molecular structure in the solid state. PMID- 11781489 TI - 2,6-diphenylpyridine-4-carboxylic acid. AB - The distinctive feature of the crystal structure of 2,6-diphenylpyridine-4 carboxylic acid, C18H13NO2, is the formation of intermolecular O-H...O hydrogen bonds that lead to the formation of centrosymmetric cyclic dimers with R2(2)(8) topology. Molecules related by translation along the b axis exhibit strong pi-pi stacking of aromatic rings, with an average interplanar distance of 3.3 A. PMID- 11781490 TI - 2,2'-[2,3-dihydro-2-(prop-2-enyl)-1H-isoindole-1,3 diylidene]bis(propanedinitrile)-tetrathiafulvalene (1/1), TCPI-TTF. AB - The title complex, C17H9N5*C6H4S4, contains pi-deficient bis(dinitrile) and TTF molecules stacked alternately in columns along the a-axis direction; the interplanar angle between the TTF molecule and the isoindolinyl C4N[C(CN)2]2 moiety is 1.21 (4) degrees. The N-allyl moiety in the TCPI molecule is oriented at an angle of 87.10 (10) degrees with respect to the five-membered C4N ring, and the four C[triple-bond]N bond lengths range from 1.134 (3) to 1.142 (3) A, with C C[triple-bond]N angles in the range 174.3 (3)-176.9 (2) degrees. In the TTF system, the S-C bond lengths are 1.726 (3)-1.740 (3) and 1.751 (2)-1.763 (2) A for the external S-C(H) and internal S-C(S) bonds, respectively. PMID- 11781491 TI - Supramolecular structures of 5-[3-(4-methylphenyl)- and 5-[3-(4-chlorophenyl)-2 propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione. AB - 2,2-dimethyl-5-[3-(4-methylphenyl)-2-propenylidene]-1,3-dioxane-4,6-dione, C16H16O4, crystallizes in the triclinic space group P-1, with two molecules in the asymmetric unit. These molecules and a centrosymmetrically related pair, linked together by weak C-H...O hydrogen bonds, form a tetramer. 5-[3-(4 Chlorophenyl)-2-propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione, C15H13ClO4, also crystallizes in the triclinic space group P-1, with one molecule in the asymmetric unit. Centrosymmetrically related molecules are linked together by weak C-H...O hydrogen bonds to form dimers which are further linked by yet another pair of centrosymmetrically related C-H...O hydrogen bonds to form a tube which runs parallel to the a axis. PMID- 11781492 TI - A comparison of the supramolecular structures of 1-(6-amino-1,3-benzodioxol-5-yl) 3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one and 1-(6-amino-1,3-benzodioxol-5-yl)-3 [4-(N,N-dimethylamino)phenyl]prop-2-en-1-one. AB - 1-(6-amino-1,3-benzodioxol-5-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, C19H19NO6, (I), contains an intramolecular N-H...O hydrogen bond and a weak C H...O hydrogen bond, which forms a C10 chain motif running parallel to the c axis. The 6-amino-1,3-benzodioxol-5-yl moieties are involved in pi-pi stacking. 1 (6-amino-1,3-benzodioxol-5-yl)-3-[4-(N,N-dimethylamino)phenyl]prop-2-en-1-one, C18H18N2O3, (II), crystallizes with two molecules in the asymmetric unit. The main feature of the supramolecular structure of (II) is the formation of a centrosymmetric hydrogen-bonded tetramer with an R8(4)(16) motif. PMID- 11781493 TI - Hexamethylenetetraminium 2,4,6-trinitrophenolate. AB - In the title complex, the 1:1 ionic adduct of hexamethylenetetraminium and 2,4,6 trinitrophenolate, C6H13N4+*C6H2N3O7-, the cation acts as a donor for bifurcated hydrogen bonds to the O atoms of the phenolate and one of the nitro groups of the 2,4,6-trinitrophenolate anion. The crystal structure is built from sheets of cations and anions, and is stabilized by intermolecular C-H...O and C-H...pi interactions. PMID- 11781494 TI - A 1:1 adduct of hexamethylenetetramine and 4-hydroxy-3-methoxybenzaldehyde. AB - In the title complex, C6H12N4*C8H8O3, the hexamethylenetetramine molecule accepts a single intermolecular O-H...N hydrogen bond from the hydroxy group of the 4 hydroxy-3-methoxybenzaldehyde moiety. The non-centrosymmetric crystal structure is built from alternating molecular sheets of 4-hydroxy-3-methoxybenzaldehyde and hexamethylenetetramine molecules, and is stabilized by intermolecular O-H...N, C H...O and C-H...pi interactions. PMID- 11781495 TI - Conformational polymorphism in a chiral spiro-cis-ansa-bridged cyclotriphosphazene derivative. AB - The reaction of spermidine with 2,2,4,4-tetrachloro-6,6 diphenylcyclotriphosphazene produces a mixture of products of which one of the fractions is a spiro-cis-ansa derivative, namely 12-chloro-14,14-diphenyl 2,6,11,13,15,16-hexaaza-1,12-diphosphatricyclo[10.3.1.0(1,6)]hexadeca-12,14 diene, C19H26ClN6P3. Recrystallization of this fraction from different solvents results in the formation of two different crystalline forms. The rod morphology formed in dichloromethane-n-hexane (1:1) produces a triclinic structure with three molecules in the asymmetric unit. These three molecules adopt different conformations as a result of two NH groups flipping in an ansa-bridged ring system. The plate morphology crystals, grown in dichloromethane-n-hexane-ethyl acetate (1:1:1), produce a C-centred monoclinic structure that adopts a conformation that is essentially the same as one of the forms in the triclinic structure. PMID- 11781496 TI - Macrocalyxin I. AB - The title compound, 2-[1,2,3,4,4a,4b,5,6,7,8,8a,9-dodecahydro-7-hydroxy-4b,8,8 trimethylphenanthren-2-yl]propenoic acid, C20H30O3, is a naturally occurring diterpenoid which was isolated from Rabdosia macrocalyx. The hydroxy and carboxy groups, which are located at the two ends of the molecule, both serve as simultaneous hydrogen-bond donors and acceptors. Two intermolecular O-H...O hydrogen bonds are present and link each molecule to four neighbours, thus forming an extensive hydrogen-bond network within the crystal. PMID- 11781497 TI - Purine-rich exon sequences are not necessarily splicing enhancer sequence in the dystrophin gene. AB - Purine-rich sequences within exons are proposed to promote proper splicing as splicing enhancers. In order to test this supposition in the dystrophin gene, which is characterized by the large size of its introns, purine-rich sequences from three exons (exons 43, 46 and 53) were examined for their splicing enhancer activity by using a Drosophila doublesex pre-mRNA. The most powerful activating effect on upstream intron splicing was seen with a sequence from exon 43. A sequence from exon 53 showed relatively low activity, whilst that from exon 46 had little effect. To characterize the splicing enhancer sequences in exons 53 and 46 further, entire exons were divided into 30nt fragments that were examined separately for their splicing enhancer activity. In exon 53, two fragments located at the 5' and 3' ends, respectively, had strong splicing enhancer activity, although they were not the most purine-rich regions of the exon. In contrast, all of the fragments derived from exon 46 had little activity. These results suggest that different exons in the dystrophin transcript are subject to different mechanisms of control by the splicing machinery. PMID- 11781498 TI - Tranilast inhibits TGF- A1 secretion without affecting its mRNA levels in conjunctival cells. AB - The present study was conducted to assess the effect of Tranilast, a drug developed as anti-keloid and anti-hypertrophic scar agent, on the level of transforming growth factor- A1 (TGF- A1) mRNA, and on TGF- A1 secretion in Chang Conjunctiva cells. TGF- A1 mRNA was not detected in Chang Conjunctiva cells by Northern blot analysis, but reverse transcriptase-polymerase chain reaction (RT PCR) analysis confirmed the presence of TGF- A1 mRNA. Tranilast, whereas the drug had no effect on the levels of TGF- A1 mRNA and cellular protein, time- and dose dependently inhibited TGF- A1 secretion from Chang Conjunctiva cells in the enzyme-linked immunosorbent assay (ELISA) analysis. TGF- A1 is suggested to cause fibroblast proliferation, that obstructs aqueous humor filtration route after glaucoma filtration surgery. Tranilast, potentially inhibiting TGF- A1 secretion, therefore, could be a promising drug to prevent from scarring after glaucoma filtration surgery. PMID- 11781499 TI - Unsaturated free fatty acids inhibit Ca2+ mobilization and NO release in endothelial cells. AB - Circulating free fatty acids (FFAs) are elevated in various disorders like states of insulin resistance, and an increase of FFAs has been reported to be associated with endothelial dysfunction. To investigate the effect of FFAs on vascular endothelial cells, we measured nitric oxide (NO) release and intracellular free calcium concentration ([Ca2+]i ) in cultured bovine aortic endothelial cells (BAECs). Monounsaturated FFAs such as oleic acid (OA) and polyunsaturated FFAs such as linoleic acid (LA) dose-dependently (10-100 Emol/L) inhibited NO release from BAECs stimulated by adenosine 5'-(3-O-thio)triphosphate (ATP AS) whereas saturated FFAs such as palmitic acid had no effect on NO release. ATP AS induced a biphasic increase in [Ca2+]i, which consisted of a rapid increase followed by a sustained increase. OA and LA inhibited ATP AS-induced Ca2+ release from intracellular Ca2+ stores and increase in Ca2+ influx from extracellular space. In addition, OA and LA rapidly decreased sustained increase in [Ca2+]i induced by ATP AS when OA or LA was added after stimulation with ATP AS. Impaired Ca2+ mobilization by unsaturated FFAs (UFFAs) was completely reversed by treatment with bovine serum albumin (1 mg/ml) indicating that inhibitory effect of FFAs was not caused by cytotoxic effect. In spite of this inhibitory effect of UFFAs, neither OA nor LA had any effect on phosphoinositide hydrolysis evoked by ATP AS. From these results, elevated UFFA may contribute to impaired NO production through inhibition of receptor-mediated Ca2+ mobilization and Ca2+ influx in pathological conditions such as multiple risk factor syndrome and insulin resistance. PMID- 11781500 TI - Usefulness of volume-rendered three-dimensional computed tomographic angiography for surgical planning in treating unruptured paraclinoid internal carotid artery aneurysms. AB - Paraclinoid internal carotid artery aneurysms are difficult to treat and difficult to visualize by using DSA, MRA, or surface-rendered 3D-CTA. Because those aneurysms are surrounded by bone, the dural ring (proximal and distal), the optic nerve, the oculomotor nerve, and the cavernous sinus. This report represents the first attempt to assess the verification of volume-rendered 3D-CTA for surgical planning in treating paraclinoid internal carotid artery aneurysms. From January, 1996 to October, 2001, we treated 15 cases of unruptured paraclinoid internal carotid artery aneurysms at Kobe University Hospital. Twelve of the patients were women and three were men, ranging age from 33 to 70 (55.7 /10.3). We studied used volume-rendered 3D-CTA to examine five patients and surface-rendered 3D-CTA for ten. Volume-rendered 3D-CTA allowed observation of the aneurysms and their necks and the surrounding structures in all cases (P<0.001), while surface-rendered 3D-CTA allowed partial observation of the aneurysms in 5 cases (50%). Volume-rendered 3D-CTA enabled virtual removal of bones by using the clip-plane editing and allowed the aneurysms to be viewed from various angles. When the pterional approach is used and the neck of the aneurysm is found to be remote from the anterior clinoid process, the anterior clinoid process need not be removed. In conclusion, for paraclinoid internal carotid artery aneurysms, volume-rendered 3D-CTA is superior to surface-rendered 3D-CTA, MRA and digital subtraction angiography in terms of visualization of the aneurysm and surrounding bones. It was great help for surgical planning in treating paraclinoid internal carotid artery aneurysms. PMID- 11781501 TI - Confirmation of correlations and common quantitative trait loci between neurotensin receptor density and hypnotic sensitivity to ethanol. AB - BACKGROUND: In previous studies, genetic correlations were observed between hypnotic sensitivity to ethanol and high-affinity neurotensin receptor (NTS1) binding. Provisional quantitative trait loci (QTLs) were identified for these traits, and some of these QTLs were found on common chromosomal regions. In continued efforts to examine the relationship between NTS1 binding capacity and hypnotic sensitivity to ethanol, studies were designed to confirm correlations between NTS1 densities in the brain, duration of ethanol-induced loss of righting reflex (LORR), and blood ethanol concentrations at regain of righting reflex (BECRR). Another purpose of the study was to confirm QTLs for these traits. METHODS: ILS X ISS F2 mice and HAS X LAS F2 rats as well as the progenitors were tested for LORR, BECRR, and NTS1 densities. Phenotypic correlations were calculated between LORR and BECRR and between these measures and NTS1 densities in striatum from both mice and rats. The F2 mice were genotyped by using polymorphic markers for five previously reported QTLs for LORR to confirm QTLs for BECRR and NTS1 densities in striatum, ventral midbrain, and frontal cortex. RESULTS: Phenotypic correlations were found between LORR and BECRR (r = -0.66 to 0.74, p < 10(-9)) and between these measures and NTS1 densities in striatum (r = 0.28-0.38, p < 10(-2)) from both mice and rats. QTLs for LORR and BECRR (lod score = 2-6) were found in common regions of chromosomes 1, 2, and 15. By using the combined results from a previous LSXSS RI study and the current results, a suggestive QTL (lod score = 3.1) for striatal NTS1 receptor densities was found on chromosome 15 at approximately 60 cM, in the same region as the chromosome 15 LORR/BECRR QTL. CONCLUSIONS: The results are in agreement with previously reported correlations and QTLs for NTS1 receptor densities and measures of hypnotic sensitivity to ethanol in mice and extend those correlations to another species, the rat. These findings support a role for NTS1 in genetically mediated differences in hypnotic sensitivity to ethanol. PMID- 11781502 TI - GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. AB - BACKGROUND: The gamma-aminobutyric acid type A receptors (GABARs) are involved in mediating some of the behavioral effects of beverage alcohol (ethanol). However, the unique pharmacological and behavioral responses conferred by each of the various receptor subunits are not well understood. METHODS: To address the role of the GABAR delta subunit in mediating ethanol responses, gene knockout mice that lack this subunit were tested for a variety of ethanol-induced behavioral responses. RESULTS: Our results indicate that, compared with controls, delta deficient mice (delta-/-) have (1) reduced ethanol consumption, (2) attenuated withdrawal from chronic ethanol exposure, and (3) reduced anticonvulsant (seizure protective) effects of ethanol. These mice demonstrate a normal anxiolytic response to ethanol and a normal hypothermic response to ethanol, and they develop both chronic and acute tolerance. CONCLUSIONS: These results further establish the link between GABARs and specific behavioral responses to ethanol and begin to reveal the role of the delta subunit in these responses. PMID- 11781503 TI - Alcohol dehydrogenase-2*2 allele is associated with decreased prevalence of fetal alcohol syndrome in the mixed-ancestry population of the Western Cape Province, South Africa. AB - BACKGROUND: Fetal alcohol syndrome (FAS) is particularly common among the mixed ancestry population of the Western Cape Province of South Africa and occurs at a frequency of 0.0392-0.0429 (39.2-42.9 of 1000) among 5- to 9-year-old school entrants. While FAS is clearly caused by an environmental insult, studies in twins and mice support a significant genetic contribution to risk for FAS. It is likely that the development of FAS following excessive alcohol exposure is influenced by genetic factors in both the mother and the child. Known polymorphisms of the alcohol dehydrogenase-2 (ADH2) gene resulting in isozymes with different alcohol oxidizing capacities were investigated as possible candidates for influencing the risk for FAS. METHODS: Genotyping was undertaken for the ADH2 locus in 56 FAS-affected children, their 56 mothers, and 178 control individuals of mixed ancestry from the same geographic region. The ADH2 alleles were analyzed for the three groups and the allele frequencies of the mother and FAS-affected children were independently compared with the control group. RESULTS: The ADH2*2 allele was found to be significantly more common in the control group than in the mothers of FAS-affected children (p = 0.025 +/- 0.004) and in the FAS subjects (p = 0.025 +/- 0.004). The ADH2*3 allele frequency was low and was not significantly different between the groups. CONCLUSION: The ADH2*2 allele is significantly more common in control individuals, suggesting that it may either confer protection or be a marker for a protective effect against FAS among individuals of mixed ancestry in the Western Cape Province of South Africa. PMID- 11781504 TI - Protein binding of alpha-hydroxyethyl free radicals. AB - BACKGROUND: The auto-oxidation of ethanol is likely to proceed via the initial formation of hydroxyethyl radicals (HERs), the one-electron oxidation product. In the laboratory, HERs can be generated by the Fenton reaction (H2O2+ Fe+2) in the presence of ethanol. We report studies on the binding of HERs to serum albumin, generated under Fenton and non-Fenton conditions. METHODS: The generation of HER was determined by electron paramagnetic resonance spectroscopy. The formation of ethanol-derived protein adducts was determined by 14C-ethanol incorporation into serum albumin and by the binding of antibodies raised against HER adducts. RESULTS: We report that serum albumin, used as a model protein, is an effective trapping agent of HERs. In addition, HER radicals covalently bind to albumin to form acid stable adducts. Unexpectedly, we found that under aerobic conditions, the incubation of 50 mM ethanol and phosphate buffer (which contains iron traces) in the absence of the Fenton reagent yields HER radicals as shown by electron paramagnetic resonance spectroscopy and the formation of acid stable protein adducts that are recognized by antibodies raised against HER radical adducts. CONCLUSIONS: Proteins (serum albumin used as a model) are avid trapping agents of HER. There are minimal requirements for the generation of HER, because in the presence of oxygen and a phosphate buffer that contains traces of iron, ethanol readily generates HERs. Thus, HER production is likely to occur in many tissues. The ability of proteins to bind this ethanol radical should be valuable in the diagnosis of alcohol abuse and may be relevant to some of the chronic effects of ethanol. PMID- 11781505 TI - Carbohydrate deficient transferrin in abstaining patients with end-stage liver disease. AB - BACKGROUND: Carbohydrate deficient transferrin (CDT), a biochemical marker of chronic alcohol consumption, is used by researchers and clinicians alike in a variety of populations. Levels of CDT may be affected by certain types of medical illnesses and conditions. Thus the interpretation of CDT results may need to be carefully examined in these populations. Because CDT is synthesized, glycosylated, and secreted by the liver, the use of CDT values in patients with liver disease has been an area of focused interest. METHODS: We evaluated the CDT values of 79 abstaining patients with end-stage liver disease. These patients were recruited from a liver transplant clinic while they were listed and waiting for transplantation. Patients were determined to be abstaining both by interview and by random blood alcohol levels in those with a diagnosis of alcoholic liver disease. The severity of the liver disease was categorized by the Child-Pugh score. Correlations were determined between CDT values and liver enzymes, and Child-Pugh scores and liver diagnosis. RESULTS: Nearly 50% of the patients had a CDT value of 2.6% or above, indicating a clinically positive value. There were strong correlations between CDT and a number of biochemical and physical variables, most importantly the Child-Pugh score (r = 0.52, p = 0.000). Specific liver diseases were not associated with absolute CDT values. However, patients with hepatitis C (HCV) had a significantly higher chance of having a clinically positive CDT compared with patients with other types of liver diseases. CONCLUSIONS: These results suggest that an elevated CDT value may not accurately represent alcohol consumption in patients with advanced liver disease. In fact, in such patients, the CDT may become a marker for the degree of liver impairment in alcoholic and nonalcoholic liver disease. CDT values should be viewed with caution in any patient with liver disease especially when the degree of cirrhosis reaches a Child-Pugh score of C (total score of 10 or above). PMID- 11781506 TI - Classification and course of alcohol problems among adolescents in addictions treatment programs. AB - BACKGROUND: This study tested whether adolescents in addictions treatment programs could be reliably classified into milder and more severe alcohol problem categories using latent class analysis, and examined the relation of latent class structure to DSM-IV alcohol diagnoses. Transition probabilities among the latent classes at 1-year follow-up and their predictors were used to characterize the short-term course of alcohol problems. METHODS: Adolescents recruited from addictions treatment were administered a modified section of the Structured Clinical Interview for the DSM (SCID) alcohol use disorders (AUD) during or shortly after addictions treatment and at 1-year follow-up. DSM-IV lifetime conduct disorder diagnosis was assessed at baseline using a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K SADS). RESULTS: A 3-class solution that represented increasing severity of alcohol problems (i.e., asymptomatic, mild, and severe) provided the best fit to the alcohol symptom data, and was consistent across gender, ethnicity, and presence of conduct disorder. Cross-classification of latent class membership with DSM-IV alcohol diagnosis indicated only a fair level of agreement. There was an overall decrease in alcohol problem severity from baseline to follow-up. Conditional transition probabilities indicated that males and those with conduct disorder, particularly for those in the severe class at baseline, had a lower likelihood of transitioning to the asymptomatic class at 1-year follow-up. CONCLUSIONS: The latent class structure of alcohol problems in an adolescent clinical sample was best represented by a 3-class severity-based model. Cross classification of latent class membership with DSM-IV alcohol diagnosis suggests the potential utility of re-organizing diagnostic criteria to better distinguish the relative severity of abuse and dependence diagnoses. Transitions between latent classes were fairly common at 1-year follow-up, and characterized by a general reduction in alcohol symptoms. PMID- 11781507 TI - Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey. AB - BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies. PMID- 11781508 TI - Expression and cytoskeletal association of integrin subunits is selectively increased in rat perivenous hepatocytes after chronic ethanol administration. AB - BACKGROUND: For normal function and survival, hepatocytes require proper cell extracellular matrix (ECM) contacts mediated by integrin receptors and focal adhesions. Previous studies have shown that chronic ethanol consumption selectively impairs perivenous (PV) hepatocyte attachment and spreading on various ECM substrates but increases expression of the beta1 integrin subunit, the common beta subunit for two major hepatocyte-ECM receptors, alpha1beta1 and alpha5beta1 integrins. This study examined the effects of ethanol treatment on the expression and cytoskeletal distribution of alpha1, alpha5, and beta1 integrin subunits, the epidermal growth factor receptor (EGF-R), and the cytoskeletal proteins focal adhesion kinase, paxillin, vinculin, and actin in periportal and PV hepatocytes. METHODS: Periportal and PV hepatocytes were isolated from control and ethanol-fed rats. For expression analysis, lysates were examined by SDS-PAGE and immunoblotting procedures. For cytoskeletal distribution studies, Triton-soluble and -insoluble (cytoskeletal) fractions from hepatocytes cultured on collagen IV were analyzed by SDS-PAGE and immunoblotting. RESULTS: Chronic ethanol administration caused PV-specific increases in expression and cytoskeletal association of the integrin subunits. Although ethanol treatment did not affect expression of the EGF-R in either cell type, it did increase the association of the EGF-R with the cytoskeleton selectively in PV hepatocytes. Ethanol treatment had no significant effect on either the expression or the cytoskeletal distribution of focal adhesion kinase, paxillin, vinculin, or actin in either cell type. CONCLUSIONS: The increases in integrin expression and cytoskeletal association observed after chronic ethanol administration suggest that a process downstream of integrin-ECM interactions is impaired selectively in PV hepatocytes, possibly involving altered focal adhesion assembly or turnover, processes essential for efficient cell-ECM adhesion. Alterations in these processes could contribute to the impaired hepatocyte function and structure observed after chronic ethanol administration. PMID- 11781509 TI - Ethanol consumption alters electroretinograms and depletes neural tissues of docosahexaenoic acid in rhesus monkeys: nutritional consequences of a low n-3 fatty acid diet. AB - BACKGROUND: Alcohol amblyopia is a rare neuropathy characterized by the development of blurred vision and a reduction in visual acuity. Further diagnostic details of this condition have shown abnormalities in the electroretinogram (ERG) that include an increase in implicit times in the a- and b-waves and a depression of b-wave amplitude. METHODS: Periodically, the ERGs and the fatty acyl composition of nervous tissue were analyzed from alcohol-consuming rhesus monkeys (Macaca mulatta) (mean consumption 2.6 g kg/day over a 5-year period) and controls that were maintained on a nutritionally sufficient diet that had low, yet adequate, amounts of linoleic acid but very low alpha-linolenic acid. RESULTS: Animals consuming alcohol had increased a- and b-wave implicit times and decreased b-wave amplitudes in their electroretinograms compared with those of the dietary control group at 2.5 and 5 years. The fatty acyl composition of brain specimens obtained by surgical biopsy at baseline, 2.5 years, and 5 years demonstrated that docosahexaenoic acid (DHA) had decreased in both groups of animals compared with baseline values. In the brains of the alcohol-treated animals, DHA was even further decreased (2.5 years: -20%; 5 years: -33%) compared with the diet controls. In the retinas of the alcohol-consuming animals at 5 years, there was a similar decrease in DHA (-35%) compared with controls. Generally, the n-6 fatty acid, docosapentaenoic acid (DPAn-6) increased in these tissues, apparently compensating for the loss of DHA. CONCLUSIONS: A reciprocal change in the DHA/DPAn-6 ratio is known to be associated with abnormal electroretinograms in a number of species. Thus, a marginal intake of n-3 fatty acids in some alcohol abusers may, in part, be responsible for the biochemical changes that underlie the diminished retinal function associated with the visual abnormalities observed in alcohol-amblyopic patients. PMID- 11781510 TI - Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFNgamma levels. AB - BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells were isolated by Ficoll density gradient and monocytes by adherence. Alcohol (0.8 g/kg body weight, an equivalent of approximately three drinks) was given to nonalcohol-consuming individuals and blood samples were collected before, 4 hr, or 18 hr after alcohol consumption. Alcohol in vitro was administered at concentrations of 25-100 mM. RESULTS: T-cell proliferation in MLR was significantly reduced in the presence of physiologically relevant concentrations of alcohol in vitro (25-100 mM ethanol) (p < 0.05). In vivo alcohol consumption also depressed proliferation in the MLR when stimulator cells were obtained 4 hr after alcohol consumption. MLR was not decreased, however, in the presence of alcohol-exposed responder cells and normal stimulator cells, suggesting that the accessory cell population and not T cells are affected by alcohol. Decreased accessory cell function was further evidenced by reduced superantigen-induced (SEB) but not mitogen-induced (PHA) T-cell proliferation in samples obtained 18 hr after alcohol intake (35% reduction). Reduced accessory cell function was not due to changes in surface expression of monocyte costimulatory molecules (HLA class I, HLA-DR, CD80, CD86, CD40). We found reduced IFNgamma, elevated IL-10, and unchanged IL-4 levels during T-cell proliferation in samples obtained 18 hr after alcohol consumption. Acute alcohol treatment resulted in increased IL-13 in the MLR. CONCLUSION: These data suggest that even on one occasion moderate alcohol intake can reduce allostimulatory T-cell activation via decreasing accessory cell function. Increased IL-10 and IL-13 plus the reduced IFNgamma production after acute alcohol use are likely to contribute to both the reduced T-cell proliferation and monocyte accessory cell function. These accessory cell mediated defects in T-cell activation may result in impaired antiviral and antitumor immunity after moderate acute alcohol use. PMID- 11781511 TI - Association of the ADH2*3 allele with a negative family history of alcoholism in African American young adults. AB - BACKGROUND: Two of the class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode for multiple isozymes that differ in their kinetic properties. Polymorphisms at both of these gene loci have been linked to alcoholism and/or alcohol-induced disabilities in some populations. At the ADH2 locus, three polymorphisms are present (ADH2*1, ADH2*2, ADH2*3). ADH2*3 allele codes for a high Km and Vmax variant that has been reported to occur exclusively in African Americans and some tribes of Native Americans. In African Americans, the presence of the ADH2*3 allele is associated with protection from alcohol-related birth defects. However, its relationship to risk for alcoholism in African Americans remains relatively unexplored. METHODS: The participants were 97 African American young adults (18-25 years old). A structured interview was used to gather information on demographics, psychiatric diagnoses, personal drinking and drug use history, and familial history of alcohol use disorders. A blood sample was obtained from each participant and leukocyte DNA extracted and genotyped for the presence of ADH2*3 alleles. The specific aim of the study was to investigate the associations between the presence of the ADH2* 3 allele and personal and family history of alcohol use/abuse. RESULTS: Thirty participants (31%) had at least one ADH2*3 allele and two were homozygous for the allele. A significant association between the presence of an ADH2*3 allele and a negative family history of alcoholism was uncovered (p < 0.04). No significant associations of an ADH2*3 allele with personal history of alcohol use disorders or with current drinking were found; however, power to detect associations was limited in this population because half the population did not drink regularly. CONCLUSIONS: Because family history of alcoholism is one of the best predictors of the development of alcohol use disorders, this pilot study suggests that, in this sample of African American young adults, the ADH2*3 allele may be associated with a lowered risk for the development of alcoholism. PMID- 11781512 TI - Summary report of a symposium: genes and gene delivery for diseases of alcoholism. AB - This article represents a summary of a symposium on genes and gene delivery for diseases of alcoholism that was held at the University of North Carolina, Chapel Hill, on May 7-10, 2001. The purpose of the meeting was to examine two key technologies: gene chip-microarrays and gene delivery. Three main pathologies associated with alcoholism--addiction, liver disease, and birth defects--were discussed. This summary of the meeting is grouped into sections on the brain, liver, and fetus. PMID- 11781513 TI - The research community and the private sector: a hands-on or hands-off relationship? AB - This article summarizes a symposium held at the 2001 Annual Meeting of the Research Society on Alcoholism (RSA) in Montreal, Canada, and was prepared on behalf of the symposium participants. The discussion focused the relationship between research and the private sector, addressing whether such a relationship is possible or even desirable and how concerns regarding the implementation of any such arrangement can be met. Although participants represented a range of views, there was general agreement on two issues--the need to keep the source of funding separate from the research itself, and the requirement for disclosure and complete transparency. PMID- 11781515 TI - The fruits of our labors: distinguishing endometrial from endocervical adenocarcinoma. PMID- 11781516 TI - Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. AB - We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction. PMID- 11781517 TI - A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas. AB - The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma. PMID- 11781518 TI - Ovarian teratomas with florid benign vascular proliferation: a distinctive finding associated with the neural component of teratomas that may be confused with a vascular neoplasm. AB - Prominent benign vascular proliferations associated with neural tissue in five cases of ovarian teratoma are described. The ages of the patients ranged from 15 to 35 years. Three of the five had tumors confined to the ovary, one had peritoneal implants, and one had widespread metastatic immature teratoma. Two of the patients are alive and well, 8 and 9 years postoperatively. Follow-up is unavailable in two cases and the final case was recent. The tumor in three of the cases had features of mature cystic teratoma including abundant mature neural tissue and, in one instance, microscopic foci of primitive neuroepithelium. The tumor in the fourth case was an immature teratoma with abundant primitive neuroepithelium, and in the fifth case was a mixed germ cell tumor, composed mostly of immature teratoma with a minor component of yolk sac tumor. In all the tumors there was a prominent vascular proliferation composed of long thin-walled, curved vessels or a solid glomeruloid arrangement. Immunohistochemistry done in two cases confirmed the vascular nature of the proliferation. Angiogenesis, likely as an expression of vascular endothelial growth factors, is a well-known phenomenon in a variety of neural and neuroendocrine neoplasms, in particular high-grade gliomas. However, very few cases of this phenomenon have been described in association with neural tissue in the ovary. Recognition of this proliferation as a benign secondary one is important to avoid misdiagnosis of a vascular neoplasm or an immature teratoma, as happened in one of our cases. PMID- 11781519 TI - Proliferative activity of benign and neoplastic endocervical epithelium and correlation with HPV DNA detection. AB - Recent studies have indicated that the use of the MIB-1 immunostaining may be useful in distinguishing endocervical neoplasia from benign nonneoplastic lesions. We sought to investigate this finding further with a specific emphasis on the common benign processes that may result in a nonspecific increase of MIB-1 staining. In this study we quantified the MIB-1 immunostaining in the mucinous endocervical epithelium (n=45) and in tubal metaplasia (n=28) during the proliferative and secretory phases (hormonal influence), in the mucinous endocervical epithelium in cases of cervicitis (inflammation) (n=10), in cases with a history of a recent biopsy (regeneration) (n=15), endocervical polyps (benign growth) (n=8), in the endocervical glands adjacent to a squamous intraepithelial lesion (human papilloma virus [HPV] infection) (n=63), and in in situ and invasive cervical adenocarcinomas (n=30). All cases with increased MIB-1 staining were subsequently tested for the presence of HPV DNA. The range of MIB-1 staining in the benign endocervical epithelium was from 0% to 48% and in the neoplastic epithelium from 25% to 84%. MIB-1 staining below 10% always reflected a benign process and MIB-1 staining higher than 50% was always associated with a neoplasia. Rare benign cases (tubal metaplasia during the proliferative phase, glands adjacent to squamous intraepithelial lesions, and cases with a history of a recent biopsy) had increased MIB-1 index, which overlapped with the neoplastic cases. In conclusion, MIB-1 is a useful marker of endocervical neoplasia, although in rare cases an overlap between benign and neoplastic cases may exist. PMID- 11781520 TI - A semiautomated test for microsatellite instability and its significance for the prognosis of sporadic endometrial cancer in northern Norway. AB - Archival histologic material from 105 women (median age 62 years) treated for endometrial cancer was investigated for the replication error phenotype indicated by the observation of widespread microsatellite instability (MSI). Polymerase chain reaction (PCR) of DNA isolated from paraffin-embedded tissue was analyzed for MSI using six microsatellite loci with a fluorescent-based detection system. Flow cytometry and morphometric investigation were performed in the same material for each of the patients. Twenty percent (21 of 105) of screened endometrial cancers were found to have high MSI at two or more of the loci tested. The mean detection frequency per marker was highest in the dinucleotide repeat sequence, D2S123, and the mononucleotide repeat sequences amplified by Bat 25 and Bat 26. Death from endometrial cancer was not related to the occurrence of MSI (p=0.6). There was no significant association between MSI and FIGO stage (p=0.5), myometrial invasion depth (p=0.8), histological grade (p=0.3), or vessel invasion (p=0.5). There were, however, more MSI cases among the group of diploid cases compared with the aneuploid and tetraploid group. MSI is not a valuable prognosticator for survival of sporadic endometrial cancer, and diploid cases are significantly more often MSI positive than aneuploid and tetraploid cases. PMID- 11781521 TI - Adenomatoid tumors of the uterus: an analysis of 60 cases. AB - Sixty cases of uterine adenomatoid tumors (ATs) are reported. All except four were incidental findings in hysterectomy specimens, three of these being discovered preoperatively as large multicystic tumors. ATs were classified into two distinctive macroscopic patterns: small, solid tumors and large, cystic ones. The 56 small, solid ATs ranged from 0.2 to 3.5 cm, (average 2.1 cm); 48 were nodular and 8 diffuse. The four large, cystic tumors ranged from 7 to 10 cm. Inflammation occurred in 65% of the tumors, and a smooth muscle reaction, identified by an increased Ki-67 index, was present in most cases. Both types were histologically similar except for the presence of short papillae in cystic tumors, which also showed serosal involvement. Both were immunoreactive for cytokeratins, calretinin, HMBE-1, and vimentin. Estrogen and progesterone nuclear receptors and EMA were negative. These tumors represent a spectrum ranging from small and solid to large and cystic ATs in the female genital tract, whereas outside the genital tract they are morphologically similar to multicystic mesothelioma. Although a reactive origin for ATs often seems plausible, especially when inflammation is present, their neoplastic nature should not be ignored. PMID- 11781522 TI - CD10 is a marker for normal and neoplastic endometrial stromal cells. AB - Using the immunohistochemical technique, we investigated the expression of CD10 in normal female genital tissues, chorionic villi and decidua of early gestation, endometriotic lesions, and uterine mesenchymal tumors. The cytoplasm of normal endometrial stromal cells was consistently positive for CD10. During early gestation, decidualized endometrial stromal cells were negative or only focally positive for CD10, whereas nondecidualized stromal cells were diffusely positive. Syncytiotrophoblast was positive for CD10 on the apical surface, whereas chorionic mesenchymal cells were diffusely positive within the cytoplasm. Cytotrophoblast and intermediate trophoblast were negative for CD10. Groups of stromal cells surrounding cervical glands were often positive for CD10. Myometrium, endometrial and cervical glands, cervical squamous epithelia, and tubal epithelia and stroma exhibited no reactivity for CD10. In endometriosis and adenomyosis, ectopic endometrial stromal cells were usually positive for CD10. Endometrial stromal tumors, including undifferentiated uterine sarcomas, mostly showed diffuse immunoreactivity for CD10. Leiomyomas and leiomyosarcomas were negative or focally (< 5% of cells staining) positive (8/12 leiomyomas and 4/8 leiomyosarcomas) for CD10, except for 1 myxoid leiomyosarcoma that showed CD10 staining in the myxoid areas. These data suggest that diffuse CD10 staining is characteristic of normal and neoplastic endometrial stromal cells, unless they are decidualized. PMID- 11781523 TI - Epithelioid endometrial and endometrioid stromal tumors: a report of four cases emphasizing their distinction from epithelioid smooth muscle tumors and other oxyphilic uterine and extrauterine tumors. AB - Three endometrial and one extrauterine endometrioid stromal tumors (three sarcomas and one stromal nodule) with a prominent component of epithelioid cells with abundant eosinophilic cytoplasm are described. The patients were 39, 48, 56 and 86 years of age. The endometrial sarcomas were described grossly as an ill defined tan nodule and "ragged and papillary," respectively, and had the typical infiltrative pattern of low-grade endometrial stromal sarcoma. The stromal nodule was a 13-cm, well circumscribed, yellow, fleshy mass. The extrauterine tumor was probably primary in the sigmoid colon. Oval to polygonal epithelioid cells with abundant eosinophilic cytoplasm accounted for 50% to 90% of the tumor cells. The cytoplasm was granular in one case. None of the tumors contained cells with a rhabdoid appearance. Nuclear and other features did not differ from those of usual endometrial-endometrioid stromal tumors except in one case in which there was greater nuclear pleomorphism. There was strong diffuse cytoplasmic immunoreactivity of all four tumors for vimentin and for CD10 in three of three tumors tested, as well as extensive and moderate reactivity for NK1/C3 and focal weak reactivity for CD68 in two of three tumors tested. Muscle actin positivity was very focal to extensive and weak to strong in all three tumors tested, mainly in the epithelioid areas; alpha-smooth muscle actin was focally to extensively positive in the epithelioid areas of two of three tumors tested; and focal strong desmin positivity (interpreted as indicating smooth muscle metaplasia) was found in the epithelioid areas of one of four tumors. A vaginal recurrence in one case had similar cytologic features to the primary tumor but when examined initially in the absence of adequate history posed diagnostic difficulty, as did evaluation of the uterine tumor in two other cases and the extrauterine tumor in the final case. The differential in these cases is primarily with an epithelioid smooth muscle tumor when they are uterine primaries. The typical infiltration facilitates this distinction in the cases of endometrial stromal sarcomas, but this feature is usually only evident in hysterectomy specimens. In limited samples such as biopsy or curettage specimens, and in some cases of recurrent tumor, awareness that endometrial-endometrioid stromal tumors can have epithelioid cells is crucial in the formulation of the differential diagnosis. Diverse oxyphilic tumors, including deciduoid malignant mesothelioma, can potentially be in the differential diagnosis with extrauterine (endometrioid) stromal sarcomas with epithelioid cells. Immunohistochemical evaluation may potentially provide major aid in diagnosis. PMID- 11781524 TI - Pseudoxanthomatous and xanthogranulomatous salpingitis of the fallopian tube: a report of four cases and a literature review. AB - The clinical and pathological features of four cases of pseudoxanthomatous salpingitis (PXS) and xanthogranulomatous salpingitis (XGS) are described. The women with PXS underwent salpingectomy for primary sterility (Case 1) and endometriosis (Case 2). The two women with XGS presented with pelvic inflammatory disease (PID) and an adnexal mass and were initially treated with antibiotics. Shortly thereafter, a left salpingo-oophorectomy (Case 3) and total abdominal hysterectomy with bilateral salpingo-oophorectomy (Case 4) were performed. In Cases 1 and 2, histological examination revealed expansion of the tubal plicae with numerous pigmented histiocytes (PXS). In Cases 3 and 4, the tubal mucosa was infiltrated by foamy histiocytes admixed with other inflammatory cells (XGS). A review of the literature revealed that most patients with PXS have a clinical history of long-standing endometriosis, whereas XGS is an unusual manifestation of chronic PID. Although PXS can be confused on histological examination with XGS, the two processes should be distinguished because of their different clinical associations and pathogenesis. PMID- 11781525 TI - Mullerianosis of inguinal lymph nodes: report of a case. AB - We report a case of florid mullerianosis involving inguinal lymph nodes, a simulator of metastatic adenocarcinoma. The patient was a 48-year-old woman with symptomatic leiomyomas and enlarged right inguinal lymph nodes. Microscopically two lymph nodes were partially or completely replaced by cystically dilated and small glands, many of which contained mucin. The larger of the two lymph nodes was completely replaced by cystically dilated structures and long branching tubular glands that focally displayed well-defined lobular and papillary patterns. The glands were lined predominantly by a single layer of columnar cells similar to those of the endocervical epithelium. The columnar cells had bland basal nuclei and abundant mucin-containing cytoplasm. Admixed with these cells were others similar to those of tubal epithelium. Some of the glands were partially surrounded by a cellular ovarian-like stroma. There was focal cytologic atypia but no mitotic figures were seen. There was also focal oxyphil cell metaplasia with atypical hobnail cells. Some cystically dilated glands that contained abundant mucin were lined by flat epithelial cells. Because of gland rupture, mucin extravasated into the stroma but did not elicit a desmoplastic response. Surgical pathologists should be aware of mullerianosis in lymph nodes to avoid confusing it with metastatic adenocarcinoma. PMID- 11781526 TI - Primary peritoneal mullerian adenosarcoma with sarcomatous overgrowth associated with endometriosis: a case report. AB - We report a primary peritoneal mullerian adenosarcoma with sarcomatous overgrowth associated with endometriosis in a 50-year-old female. The tumor formed multiple peritoneal masses occupying the pelvis and subdiaphragmatic space. Histologically, the tumor was composed of benign-appearing mullerian glands surrounded by a sarcomatous stroma. In addition, one perisplenic mass was largely devoid of the epithelial component and was of higher grade than the remaining lesions. Multiple foci of endometriosis were associated with the pelvic masses. To our knowledge, primary peritoneal mullerian adenosarcoma with sarcomatous overgrowth associated with endometriosis has not been previously reported. PMID- 11781527 TI - Epithelioid angiomyolipoma of the ovary: a case report and literature review. AB - Angiomyolipoma (AML) is a benign mesenchymal neoplasm that mainly occurs in the kidney either sporadically or in patients with tuberous sclerosis complex (TSC). Extrarenal AML is uncommon. We describe a 39-year-old female with a history of TSC and bilateral multicentric renal AML who presented with a persistent cystic ovarian mass that fluctuated in size during 2 years of ultrasonographic observation before its removal by salpingo-oophorectomy. The 4.5-cm mass was solid and cystic and tan-yellow. Microscopic examination showed an admixture of epithelioid cells, smooth muscle bundles, large thick-walled blood vessels, and mature adipose tissue. The epithelioid cells had abundant eosinophilic cytoplasm and many had bizarre atypical nuclei including multinucleated forms. Mitoses were rare. Typical smooth muscle cells and the epithelioid cells were strongly immunoreactive for HMB-45. To our knowledge, this represents the first report of an AML arising in the ovary. The differential with other oxyphilic tumors of the ovary is discussed. PMID- 11781528 TI - Mature cystic teratoma of the ovary with struma and benign Brenner tumor: a case report with immunohistochemical characterization. PMID- 11781529 TI - Ovarian mixed germ cell tumor with predominance of polyembryoma: a case report with literature review. AB - An ovarian mixed germ cell tumor in a 34-year-old woman contained a predominant component of polyembryoma as well as foci of choriocarcinoma, yolk sac tumor, and immature teratoma. No previous cases of identical composition have been found in the literature. PMID- 11781530 TI - Immature teratoma of the ovary with a minor rhabdomyosarcomatous component and fatal rhabdomyosarcomatous metastases: the first case in a child. AB - A case of ovarian immature teratoma with rhabdomyosarcomatous recurrence in a 6 year-old girl is described. The primary tumor consisted of a dermoid cyst and a solid nodule composed of mature and immature mesenchymal tissue. The most immature mesenchymal cells showed no distinctive differentiation except for focal rhabdomyoblastic differentiation. The primary tumor was diagnosed as immature teratoma, grade 2, stage IIa. Despite left oophorectomy and excision of uterine serosal implants, chemotherapy, and radiation, four intrapelvic recurrences developed within 3 years. Although the primary tumor contained only a few rhabdomyoblasts, the recurrent tumors became increasingly rhabdomyosarcomatous. The patient died of systemic disease 3 years after presentation. This case and previous reports indicate that the prognosis of patients with ovarian immature teratoma with rhabdomyosarcomatous recurrence is poor and similar to that of primary ovarian rhabdomyosarcoma. PMID- 11781531 TI - Polypoid Brenner tumor of the uterus. AB - Extraovarian Brenner tumors (BT) are very rare. We report such a tumor that was an intracavitary polyp in the uterus of a 63-year-old woman. The differential diagnosis included a pure transitional cell tumor, a mixed mullerian tumor, and a uterine tumor resembling an ovarian sex cord tumor. The histogenesis of BT remains controversial; in this particular case the location of the BT suggests a mullerian origin. PMID- 11781532 TI - History of gynecological pathology. XI. Dr. Oskar Frankl. PMID- 11781535 TI - Homosexual orientation in males: evolutionary and ethological aspects. AB - Evolutionary theory proposes that adaptive traits are reproduced more successfully than maladaptive traits. Accordingly, natural selection should favor heterosexuality as it facilitates reproduction and the propagation of genes. However, the question becomes, what has maintained homosexuality in a small but consistent percentage of the human population? Research into the evolutionary and hormonal factors associated with a homosexual orientation have yielded provocative but inconsistent results. It also suggests that human sexual orientation, and in particular homosexual orientation, is too complex to be described by one simple model or a single research discipline. The current paper treads a new path and emphasizes an integrative approach for the understanding of homosexuality. The authors examine the combined effects of evolutionary factors and neurohormonal processes on the development of a homosexual orientation. It is suggested that research into the topic could benefit from an examination of and change in some of the assumptions upon which much past research has been based. PMID- 11781536 TI - Genetic and epigenetic effects on sexual brain organization mediated by sex hormones. AB - Alterations of sex hormone levels during pre- or perinatal sexual brain organization - responsible for long-term changes of gonadotropin secretion, sexual orientation, and gender role behavior - can be caused by: 1. Genetic effects, i.e. mutations or polymorphisms of a) 21-hydroxylase genes on chromosome 6, b) 3beta-hydroxysteroid dehydrogenase genes in chromosome 1 or c) X chromosomal genes, and 2. Epigenetic effects, such as a) stressful situations - especially in combination with mutations - and b) endocrine disrupters, e.g. the pesticide DDT and its metabolites, which display estrogenic, antiandrogenic, and inhibitory effects on the enzyme 3beta-hydroxysteroid dehydrogenase leading to increased levels of dehydroepiandrosterone and its sulfate as precursors of endogenous androgens and estrogens. In connection with the introduction and extensive use of the pesticide DDT, the following findings were obtained in subjects born before as compared to those born during this period: 1. The prevalence of patients with polycystic ovaries (PCO), idiopatic oligospermia (IO), and transsexualism (TS) increased significantly (about 3-4 fold). 2. Partial 21-hydroxylase deficiencies were observed in most patients with PCO and TS and some patients with IO born before this period. 3. In contrast, most patients with PCO and TS and several patients with IO born during the period of massive use of DDT displayed clearly increased plasma levels of dehydroepiandrosterone sulfate (DHEA-S) and DHEA-S/cortisol ratios suggesting partial 3beta-hydroxsteroid dehydrogenase (3beta-HSD) deficiencies. Interestingly enough, geneticists could not find any mutations of 3beta-HSD genes in such subjects. However, o,p'-DDT and/or its metabolite o,p'-DDD are strong inhibitors of 3beta-HSD, indicating their possible co-responsibility for such life-long ontogenetic alterations. Finally, some data suggest that endocrine disrupters may also be able to affect the development of sexual orientation. PMID- 11781537 TI - Biology of cancer: thermodynamic answers to some questions. AB - All the theories of carcinogenesis have properly described this event from methodologically different points of view (medical, biological, social, biochemical psychological etc.). The point is that one should understand the thermodynamical rules underlying each of these approaches. On this level of knowledge, quantum thermodynamics combines matter and energy, while technical quantization in a novel way differentiates precancerous states as the dissipathogenic ones from the neoplasms as the newly formed dissipative structures (systems). From the essential nature of the neoplasm one can derive some general rules of therapy which focus mainly on: 1 degrees prevention and therapy of the dissipathogenic states, 2 degrees strengthening of the regenerative and defensive mechanisms of the organism and, finally, 3 degrees removal of neoplastic changes as widely as necessary but also as sparingly as possible. For a long time, these rules have been observed in reverse order. That cannot improve the medical outcome, which has not changed for a few dozen years, i.e. recovery depending on the clinical level at the moment of the diagnosis. PMID- 11781539 TI - Changes in the sensitivity of gonadotrophin axis to leptin during sexual maturation in female rats. AB - OBJECTIVES: The aim of the present paper was to determine the sensitivity of the GnRH-LH axis to leptin administration during sexual maturation in female rats. METHODS: For this purpose the hypothalamic concentration of GnRH, the pituitary content and the plasmatic levels of LH were determined in prepubertal (15 days of age) and peripubertal female rats (30 days of age), treated with leptin at a dose of 30 microg/kg. i.p. in a single injection, 90 min before sacrifice. RESULTS: The results indicate that leptin significantly increased the GnRH concentration at 15 days of age (p <0.01). At 30 days of age the hormone did not significantly modify the hypothalamic GnRH content. Leptin increased the pituitary LH levels, both in prepubertal and peripubertal rats. Nevertheless, while the increase at 15 days of age was around 180%, in peripubertal rats it was about 51,2 %. In spite that leptin significantly increased LH plasmatic levels at both ages (p < 0.01 ), in rats of 15 days of age leptin increased LH in about 244%, at 30 days of age this increase was only about 102%. CONCLUSION: These results clearly demonstrated that leptin has stimulatory effect on gonadotrophin axis been higher in prepubertal than in peripubertal rats. On these basis, and on the results of previous papers, (in which it has been demonstrated that the hypothalamic control of gonadotrophins by neurotransmitters and neuromodulators also showed qualitative and quantitative changes during sexual maturation), it is proposed that these differences are connected with the maturation of the neuroendocrine mechanisms involved in the regulatory action of leptin on the gonadotrophins axis. PMID- 11781538 TI - Aflatoxin B1 induces apoptosis in rat liver: protective effect of melatonin. AB - OBJECTIVES: A study of liver apoptosis after aflatoxin B1 (AFB1) administration and the effect of melatonin (MEL) was investigated in male rats. METHODS: Five groups of 15 rats each were used: controls, MEL Soln-treated rats (MEL dose,5 mg/Kg body wt), AFB1-treated rats (50 microg/Kg body wt), MEL Soln+AFB1-treated rats, and MEL micro-capsules (MEL-MC)+ AFB1-treated rats. After 8 weeks of treatment, biochemical measurements in liver homogenates and histopathological examination of liver sections of different groups using light and transmission electron microscope were done. The caspase-3 enzyme activity, apoptotic marker, was determined in liver tissues. Because hepatic antioxidants represent the major defence against toxic liver injury, and they act as anti-apoptosis. So, the levels of glutathione (GSH) and zinc (Zn) and the enzyme activities of glutathione reductase (GR), glutathione peroxidase (GSPx) and glutathione-S transferase (GST) were determined. In addition, the levels of malondialdehyde (MDA), a lipid peroxidation product, and nitric oxide (NO) levels were measured. RESULTS: The levels of caspase-3 activities in AFB1 group were significantly higher than control group. The apoptosis was associated with degenerative and necrotic changes in the hepatocytes. Concomitantly, the levels of MDA and NO in liver tissues were significantly increased while the levels of GSH, Zn and enzyme activities of GSPx and GR in liver tissues were significantly decreased in AFB1 group compared to their levels in controls. Caspase-3 activity was positively correlated with MDA while negatively correlated with GSH, GSPx and GR in rat livers treated with AFB1. The apoptotic rate was significantly reduced when MEL co-administrated with AFB1. In rats which received MEL with AFB1, the levels of MDA and NO in liver tissues were significantly reduced while GSH and Zn levels and GSPx, GR and GST activities were significantly increased compared to AFB1 group. When MEL-MC co-administrated with AFB1 appeared more effective in reduction of apoptotic rate as detected by decline of caspase-3 activities (inhibition 66.82%) and confirmed by histopathology. CONCLUSION: AFB1 can lead to direct or indirect caspase-3 activation and consequently to apoptosis in rat liver. MEL treatment of rats could enhance hepatic antioxidant/detoxification system which consequently reduce the apoptotic rate and the necrobiotic changes in the liver. MEL-MC exhibited an efficient protective effect against AFB1. Thus, clinical application of MEL as therapy should be considered in cases of aflatoxicosis. PMID- 11781540 TI - Melatonin shortens the survival rate of Ehrlich ascites-inoculated mice. AB - OBJECTIVES Pineal gland may have a role in organism's protection against cancer. Melatonin as well as still unidentified low-weight molecular pineal substance(s) have been reported to have growth inhibitory effect on different tumor cells. We tested the influence of melatonin and of a bovine pineal extract on the survival rate of AKR mice inoculated with Ehrlich ascites. The tumor is known to have an accelerated development after pinealectomy. MATERIAL AND METHODS: Male AKR mice, kept under a 14/10 hours - Light /Dark cycle, were inoculated intraperitoneally (i.p.) with 1.5x 10(6) Ehrlich ascites cells. On day three after inoculation the animals were divided in three groups (n=10). Each animal received i.p. daily (20.00H), until their death, 250 microl of solution containing melatonin (250 microg), pineal extract (equivalent of 1 bovine pineal gland) or saline. RESULTS: The average survival rate of the animals treated with melatonin was shorter (14.8+/-2.23 days) compared to control animals (21.9+/-2.21 days)(p=0.01). The animals treated with the pineal extract had a longer survival rate (22.6 +/- 1.8 days) but not statistically significant. The pineal extract was not available for testing at higher doses. CONCLUSION: In our model, melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions. PMID- 11781541 TI - GnRH pulsality and the differential activation of the rat luteinizing hormone subunit genes in the anterior pituitary gland. AB - Detailed studies have been focused on the mechanisms by which the rat alpha and LHbeta genes are differentially regulated by GnRH and indicate that differential sensitivity to the second messenger exists in a physiological context. Differential signaling from the GnRH receptor may be a mechanism for preferential regulation of luteinizing hormone subunit gene transcription; however which of these genes are specifically regulated by PKC or calcium and how GnRH pulsatility could preferentially activate individual pathways of second messengers within gonadotrope cells remain unclear. Several transcription factors that have profound effects on basal and/or GnRH-stimulated LHbeta gene promoter activity have been identified: SF-1, Egr-1, Sp-1. A model explaining possible interactions among them in mediating GnRH responsiveness of the LHbeta gene has been proposed: Sp1, SF-1 and Egr-1 form a tripartite GnRH response element which is sensitive to the spacing changes between the upstream Sp1 binding sites and the downstream SF 1/Egr-1 binding elements and SF-1 plays a critical role in integrating the effects of Sp1 and Egr-1. GnRH responsive element located on LHbeta gene promoter in position between -495 to -342 has been identified. At 3'-end of the promoter three Sp-1 binding sites have been identified: position -416, sequence: GGGGGCTGGG and two sites almost completely overlapping, position -403, sequence; GGGGCGGCGCCCA while at the 5'region of the promoter one Sp-1 binding site exists: position -450, sequence: ACCACACCCATTTTTGG. The 5'Sp1 site overlaps a CArG box (at -443 to -434, sequence: CCATTTTTGG) which seems to be essential in LHbeta gene sensitivity for pulsatile GnRH stimulation. PMID- 11781542 TI - The effect of light regimen and melatonin on the development of spontaneous mammary tumors in HER-2/neu transgenic mice is related to a downregulation of HER 2/neu gene expression. AB - OBJECTIVES AND DESIGN: The effect and the mechanism of light regimen and melatonin on the development of mammary tumors in HER2/neu transgenic mice were investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen (LD) or constant light illumination (LL) and a part of each group was given melatonin (20 mg/l) during the night time. RESULTS: The exposure to LL failed to change the incidence of spontaneous mammary adenocarcinoma development, the size of mammary tumors, as well as the incidence and size of lung metastases. However, the number of tumors per mouse was significantly increased in the LL group as compared to the LD group. The number of mice bearing 4 and more tumors was higher in the LL group than in the LD group, whereas the number of mice bearing 1 to 3 tumors was lower in the LL group in comparison with the LD group. Melatonin decreased the incidence and size of mammary adenocarcinomas, and the incidence of lung metastases in the LD group but not in the LL group. The mean number of tumors per mouse was not changed by melatonin treatment in both light regimens. The number of mice bearing 4 and more tumors was reduced by melatonin more significantly in the LL group than in LD group. Melatonin treatment resulted in a 2.5-fold reduction in the expression of HER-2/neu mRNA in mammary tumors from HER-2 /neu transgenic mice. CONCLUSION: The data demonstrate the influence of the LD light regiment and melatonin treatment in the development of spontaneous mammary tumors in HER-2/neu mice suggesting a melatonin-dependent modulation of HER-2/neu gene expression in mammary adenocarcinoma. PMID- 11781543 TI - Effects of pinealectomy on the circadian release pattern of leptin in male rat. AB - OBJECTIVES: Exogenous and endogenous melatonin decrease leptin release. It is not known whether melatonin also has an effect on circadian release pattern of leptin. So, this study was planned to investigate the possible changes in the circadian release of leptin following pinealectomy. METHODS: A group of rats were surgically pinealectomized while some others were exposed to sham operation. The animals were decapitated at 13.30 p.m. and 01.30 a.m. Serum leptin levels were measured by radioimmunoassay. RESULTS: Serum leptin levels at 13.30 p.m. were lower than the values at 01.30 a.m. in both pinealectomized (P<0.002) and sham rats P<0.001). Serum leptin levels measured at 13.30 p.m. and 01.30 a.m. were significantly elevated (P<0.05 and P<0.01, respectively) in the pinealectomized rats in comparison to sham animals. CONCLUSION: The circadian release of leptin does not seem to be regulated by melatonin release from the pineal gland whereas melatonin, physiologically released, may have a decreasing effect on leptin release. PMID- 11781544 TI - Cellular localization of a renin-like enzyme in leeches. AB - OBJECTIVES: The purpose of this study was to localize in leeches the renin-like enzyme previously characterized as well as the leech angiotensin-converting like enzyme (ACE). METHODS: Immunocytochemical as well as whole mount experiments were performed with an antibody raised against a fragment of the leech renin-like enzyme (VLWAAEKTQLDTGSS) and with anti-leech ACE. RESULTS: Anti-leech renin stains the vascular pole of the glomerulus and the afferent arteriole of the rat kidney. Immunostaining of leech sections revealed labeling in neurons and glial cells of the central nervous system (CNS), immunocytes and the nephridial canal, canaliculi and the periphery of the ciliated funnel, as well as the epithelium lining nephridia. Co-localization between antibodies raised against this fragment and a fragment of leech angiotensin-converting enzyme was demonstrated in neurons and glial cells of the leech CNS, as in vertebrates MAIN FINDING: Leech renin is localized in leeches like in vertebrate in the excretory system and in the nervous system. CONCLUSIONS: Our findings suggest the presence of a renin angiotensin system involved in osmoregulation in leeches. PMID- 11781545 TI - Neurotrophin and GDNF expression increases in rat adrenal glands during experimental colitis. AB - OBJECTIVES: Neurotrophins and GDNF have been recently recognized as important local regulators of inflammatory processes of the gut. RESULTS: We now demonstrate that experimental TNBS-colitis is associated with the increased expression of neurotrophins and GDNF in the adrenal glands. In histological sections of the adrenals from untreated control animals, faint immunolabeling for BDNF, NT-3 and NGF was detectable in the adrenal cortex, with some additional labeling for NGF over the adrenal medulla, whereas GDNF immunolabeling was confined to the adrenal medulla. Induction of TNBS-colitis markedly increased NGF, BDNF, and NT-3 expression within the adrenal cortex after 8 h. NGF declined to basal levels after 7 days. In case of BDNF and NT-3 basal expression levels were reached after 14 days. GDNF expression was robustly upregulated in the adrenal medulla 8 h after induction of colitis and stayed elevated for up to 14 days. CONCLUSION: Together these observations suggest that neurotrophins and GDNF might act as local modulators of components of the HPA-axis during peripheral inflammation. PMID- 11781546 TI - Neuroimmunology of opioids from invertebrates to human. AB - There is today growing evidence that the nervous and the immune systems can exchange information, mainly through small molecules, either cytokines or neuropeptides. Furthermore, it appears that some so-called neurotransmitters like neuropeptides can function as endogenous messengers of the immune system, and that they most likely participate in an important part in the regulation of the various components of the immune response. In this context, it is widely accepted that all organisms have processes that maintain their state of health. Failure of these processes, such as those involving naturally occurring antibacterial peptides, may lead to pathological events. The presence of antibacterial peptides on both proenkephalin invertebrate (Leeches) and vertebrate (Human) neuropeptide precursors such like enkelytin, peptide B, further supports the hypothesis that some of neuropeptide precursors are implicated in immune response. Indeed, their peptides, with their high antibacterial activities further associate opioid peptides with immune related activities. We surmise that immune signalling molecule may lead to enhanced proenkephalin proteolytic processing by prohormone convertase freeing both opioid peptides and antibacterial peptides during innate immune response. However, because it is necessary to modulate inflammation, invertebrates like leeches are also able to synthesize panoply of messengers that modulate inflammation e.g. endocannabinoids, opiates and pro-opiomelanocortin derived peptides such like adenocorticotrophin and melanostimulating hormone. This demonstrates that the equilibrium between the stimulation and the inhibition of the immune response has evolved sooner that it can be thought. PMID- 11781548 TI - Acute changes in systolic and diastolic events during clinical coronary angioplasty: a comparison of regional velocity, strain rate, and strain measurement. AB - Ultrasound-derived natural strain rate and strain are new Doppler myocardial imaging (DMI) parameters, which can measure local deformation independently of overall heart motion and thus could better characterize local contractility than DMI velocities alone. This study was undertaken to evaluate the relative benefits of regional velocity, strain rate, and strain measurements in detecting the range of acute changes in regional myocardial function in the "at-risk" zone during coronary angioplasty. Sixty-one patients (aged 63 +/- 12, 18 women) with stable angina pectoris were studied before, at the end of, and during recovery from a 60 second percutaneous transluminal coronary angioplasty (PTCA) balloon occlusion. High frame rate (147 fps) color DMI regional velocity data were derived from basal posterior (parasternal view) and mid, apical septal (apical view) "at-risk" segments as well as from the corresponding segments in healthy subjects and analyzed offline for velocity (VEL), strain rate (SR), and strain (epsilon) measurements. Coronary occlusion resulted in the reduction in VEL(SYS), SR(SYS), and epsilon(SYS) values for both radial (RCA/CX occlusion) and longitudinal data (LAD occlusion) in all segments analyzed. Velocity parameters alone failed to distinguish between baseline and occlusive measurements in the "at-risk" segments with visually abnormal baseline function. SR(SYS) and epsilon(SYS) had a higher diagnostic accuracy (sensitivity 75%, 80% and specificity 80%, 82%, respectively) than VEL(SYS) velocity alone (sensitivity 68%, specificity 65%,) for identifying acute ischemia in either baseline normal and abnormal segments. DMI-derived indexes can identify and quantify the spectrum of acute systolic and diastolic ischemic changes induced during clinical PTCA. The quantitation of regional deformation rather than motion would appear to be more appropriate in detecting and quantifying acute ischemic changes in myocardial function, especially in segments with pre-existing abnormal function. PMID- 11781549 TI - Strain rate imaging for the assessment of preload-dependent changes in regional left ventricular diastolic longitudinal function. AB - BACKGROUND: Strain rate imaging is a new and intriguing way of displaying myocardial deformation properties by means of echocardiography. With high frame rate strain rate imaging we observed a spatial inhomogeneity in diastolic longitudinal strain rates in healthy persons. A base-to-apex time delay in diastolic lengthening could be seen both in early diastole and at atrial contraction. METHODS AND RESULTS: We investigated this consistent finding and its dependence on loading conditions in 20 healthy volunteers. Propagation velocities of lengthening of 91 +/- 31 cm/s (E-wave) and 203 +/- 11 cm/s (A-wave) at rest (equal to time delays of 104 +/- 29 ms and 56 +/- 24 ms, respectively) increased significantly to 101 +/- 27 cm/s (E) and 283 +/- 17 cm/s (A) with lifting the volunteers' legs. Applying nitroglycerin sublingually and sitting upright significantly decreased propagation velocities (E-wave 76 +/- 20 cm/s, A-wave 172 +/- 93 cm/s and E-wave 66 +/- 17 cm/s, A-wave 150 +/- 64 cm/s, respectively). Free lateral walls showed a lower propagation velocity than septal walls. CONCLUSION: We conclude that the propagation velocities of left ventricular lengthening waves are dependent on preload changes and increase with increasing preload. PMID- 11781550 TI - Quantification of regional left and right ventricular radial and longitudinal function in healthy children using ultrasound-based strain rate and strain imaging. AB - BACKGROUND: Noninvasive assessment of left (LV) and right (RV) ventricular function in children could benefit from a technique that would characterize local myocardial deformation. Color Doppler myocardial imaging (CDMI) allows the calculation of either local longitudinal or radial Strain Rate (SR) and Strain (epsilon). To determine the clinical feasibility and reproducibility of longitudinal and radial SR and epsilon, the following study was carried out. METHODS: CDMI data were obtained from 33 healthy children (4-16 years). To quantify regional longitudinal and radial function SR and epsilon data were obtained from apical and parasternal views respectively. From the extracted SR curves, peak values for systole, early diastole, and late diastole were calculated. From the extracted epsilon curves the systolic, early and late diastolic epsilon values were calculated. RESULTS: LV longitudinal deformation were homogeneous for LV basal, mid and apical segments (peak systolic SR: -1.9 +/ 0.7 s(-1), systolic epsilon -25% +/- 7%). Longitudinal SR and epsilon values were significantly higher and heterogeneous in the RV (compared with LV walls) and were maximal in the mid part of the RV free wall (peak systolic SR: -2.8 +/- 0.7 s(-1), systolic epsilon -45% +/- 13%). The RV inferior wall showed homogeneous but lower longitudinal SR and epsilon values. The LV systolic and diastolic SR and epsilon values were higher for deformation in the radial direction compared with the longitudinal direction (radial peak systolic SR: 3.7 +/- 0.9 s(-1), radial systolic epsilon 57% +/- 11%; P <.0001). The interobserver variability for radial systolic epsilon and SR was 10.3% and 13.1%, respectively. CONCLUSION: Ultrasound-based Strain SR/epsilon imaging is a practical, reproducible clinical technique, which allows the calculation of regional longitudinal and radial deformation from both LV and RV segments. The combination of regional SR/epsilon indices and the timing of specific systolic or diastolic regional events may offer a new noninvasive approach to quantifying regional myocardial function in congenital and acquired heart disease in children. PMID- 11781551 TI - Influence of body size and age on maximal diastolic velocity of mitral annulus motion. AB - BACKGROUND: Maximal long-axis relaxation velocity (RV(m)), measured from the mitral annulus motion (MAM), has recently been suggested as an index of left ventricular (LV) diastolic function. M-mode recording and pulsed tissue Doppler have been used. Regarding the M-mode method, reference values have not been presented previously. In the current study, therefore, the influence on RV(m) of such variables as age, body size, heart rate, and blood pressure was investigated to obtain adequate reference values. METHODS AND RESULTS: Fifty-seven healthy subjects were included in the study. RV(m) was recorded by M-mode echocardiography from apical 4- and 2-chamber views from 4 sites of the mitral annulus. Multiple regression analysis showed that heart rate ought to be taken into account when reference values are calculated for children and adolescents, and age must be considered in adults. For reference values in children and adolescents, the following equation is suggested: RV(m) = 171 - 0.54 x heart rate (SEE = 18.7). In adults over 18 years, the suggested equation is RV(m) = 163 - 1.29 x age (SEE = 8.4.) PMID- 11781552 TI - Myocardial texture analysis in idiopathic dilated cardiomyopathy: prediction of contractile reserve on dobutamine echocardiography. AB - Conventional resting echocardiography is not able to predict contractile reserve (CR) of patients with idiopathic dilated cardiomyopathy. The aim of this study was to investigate whether the videodensitometric myocardial texture analysis could predict the CR of these patients. Myocardial texture analysis was performed on echocardiographic digitized images of 27 patients with IDC through a calibrated 256 gray level digitization system. Cyclic variation (CV) index of myocardial mean gray level (MGL) was calculated according to the formula: (MGL(diast) - MGL(syst))/ MGL(diast) x 100. CR was defined as the %-change of ejection fraction by 10 microg/kg per minute dobutamine infusion. A clinical follow-up was also performed for all patients for an average of 8 +/- 3 months. CR ranged from -1.8% to 50.3%. CV index of both septum and posterior wall (PW) was the single parameter significantly correlated to CR (r = 0.69 and r = 0.77, respectively, P <.0001 for both). The mean resting CV index of septum and PW were significantly lower in patients with CR less than 17%-median value of all subjects-(5.7 +/- 5.6 vs 16.9 +/- 7.9 and 5.4 +/- 5.9 vs 16.1 +/- 6.4, respectively, P <.0001 for both). A CV index of 10% for both septum and PW yielded a sensitivity of 77% and 84%, and a specificity of 84% and 84% for predicting diminished CR, respectively. The event-free survival rate was significantly lower in patients with CR less than 17% (61.5% vs 92.8%, P <.05). The CV index of both septum and PW were also significantly lower in patients with cardiac events (13.6 +/- 8 vs 4.3 +/- 6, P <.05 and 14.7 +/- 7 vs 4.1 +/- 7, P <.01, respectively). Ultrasonic myocardial texture analysis in idiopathic dilated cardiomyopathy has a high ability to discriminate the patients with and without preserved CR, and patients with unfavorable outcome as well. PMID- 11781553 TI - Use of atropine to maintain higher heart rate after exercise during treadmill stress echocardiography. AB - The sensitivity of treadmill stress echocardiography (SE), which is extensively used as a noninvasive test to detect myocardial ischemia, is contingent on the rapid acquisition of 2-dimensional echocardiographic (2D) images immediately after exercise, before a substantial decrease in heart rate (HR). This test is technically challenging and needs proficient sonographers to obtain the images rapidly. This study was designed to determine whether administration of atropine at peak exercise would maintain a higher HR longer after exercise, thereby facilitating acquisition of images. Two comparable groups of patients were randomized to receive either 0.5 mg atropine intravenously (i.v.) (n = 20), or no medication (n = 19) at peak exercise. HR was significantly higher in the atropine group compared with the control group (P <.05) at 60, 90, and 120 seconds after exercise. There were no serious complications in either group. Atropine can be safely used to maintain a higher HR after exercise during SE, thus reducing the technical challenge of obtaining postexercise 2D images while HR remains elevated. PMID- 11781554 TI - Importance of transducer displacement and tilting on three-dimensional echocardiographic volume assessment using apical or off-axis rotational acquisition: an in vitro study. AB - OBJECTIVE: The goal of this study was to assess effects of translation (horizontal displacement) and angulation (transducer tilting) on 3-dimensional (3D) echocardiographic volumes of both balloons and human left ventricles after autopsy. METHODS: Six water-filled (non-) aneurysmatic balloons of 150, 250, and 350 mL and 3 hearts of different sizes and shapes were suspended upright in a water bath. Angulation and/or translation was performed respectively by tilting the transducer with a mechanical arm in a vertical plane relative to the balloon tip or true apex of the hearts and by shifting the water bath in the same vertical plane. For balloon and left ventricular (LV) volume assessment, a 3D conical data set was obtained by TomTec rotational acquisition in combination with a HP Sonos 5500 ultrasound machine. RESULTS: For the 6 balloons, translation from 1 to 4 cm yielded volumes of up to 74% of the optimal volume (100%); angulation of 10 degrees or 20 degrees, volumes of up to 80% and 34%. Translation with 10-degree angulation yielded volumes up to 64%; for 20-degree angulation and translation, there was no volume loss. Results were similar for the left ventricles. CONCLUSIONS: Even minor angulation or translation of the transducer yields substantial underestimation of the true volume. Off-axis para-apical views, however, defined as angulation of 20 degrees and greater than 0.5 cm translation in this in vitro model, obviate volume underestimation. Such views in patients, if obtainable, may be an attractive alternative for conventional apical 3D acquisition, especially in dilated and aneurysmatic hearts. PMID- 11781555 TI - Direct quantification of transmitral flow volume with dynamic 3-dimensional digital color Doppler: a validation study in an animal model. AB - Accurately quantifying transmitral flow volume is clinically important not only as a measure of cardiac output, but also as a value from which to subtract aortic flow, for determining the severity of mitral regurgitation. However, controversy exists over the accuracy of pulsed Doppler for mitral flow quantification because of the complexity of mitral flow geometry and dynamic changes in flow profile and flow area. To explore the feasibility of directly quantifying transmitral flow volume with a newly developed dynamic 3-dimensional digital color Doppler technique, this in vivo experimental study was conducted to validate the method. Eight open chest sheep were imaged with a multiplane transesophageal (TEE) probe placed on the heart for digital 3-dimensional gated acquisition of mitral inflow over a 180-degree acquisition. The digital velocity data were contour detected for flow area after computing the velocity vectors and flow profile perpendicular to a spherical 3-dimensional surface across the mitral annulus. Flow areas and actual velocities were then integrated in time and space and the resulting flow volumes were compared with those obtained by a reference electromagnetic flowmeter on the aorta for 26 steady hemodynamic states. The flow volumes correlated closely to the electromagnetic references (y = 0.87x + 2.49, r = 0.92, SEE = 1.9 Ml per beat). Our study shows that transmitral flow volume can be accurately determined in vivo by this dynamic 3-dimensional digital color Doppler flow quantification method. PMID- 11781556 TI - Rapid quantitative assessment of myocardial perfusion: spectral analysis of myocardial contrast echocardiographic images. AB - We described a novel rapid spectral analysis technique performed on raw digital in-phase quadrature (IQ) data that quantitatively differentiated perfused from nonperfused myocardium based on the simultaneous comparison of local fundamental and harmonic frequency band intensity levels. In open-chest pigs after ligation of the left anterior descending coronary artery (LAD) and continuous venous contrast infusion, the fundamental-to-harmonic intensity ratio (FHIR) for samples placed within the left ventricular (LV) cavity (10.8 +/- 1.7 dB) and perfused myocardium (13.7 +/- 1.6 dB) were significantly (P <.001) lower than for nonperfused myocardium (27.1 +/- 2.9 dB). In attenuated images, the FHIR for the LV cavity and perfused myocardium were also significantly (P <.05) lower than for the nonperfused myocardium (21.4 +/- 3.0 dB, 34.4 +/- 3.2 dB, and 40.2 +/- 4.4 dB, respectively). Spectral properties of contrast microbubbles, as characterized by the FHIR, allow for rapid quantitative assessment of myocardial perfusion from data contained in a single-image frame, without requiring background image subtraction and image averaging. PMID- 11781557 TI - Left anterior descending coronary artery flow and its relation to age in children. AB - Recent advances in Doppler and color echocardiographic techniques enable coronary flow dynamics to be estimated even in children. To assess quantitatively left anterior descending coronary artery (LAD) volumetric flow and to determine its relation to age and left ventricular (LV) mass, healthy children participated in a study that used high-frequency transthoracic echocardiography. We also studied whether Doppler echocardiography can reliably measure LAD flow in a clinical setting. In 57 healthy children, 2-dimensional echocardiography was used to measure the diameter and cross-sectional area of the LAD and LV mass. LAD peak flow velocity, flow velocity integral, and flow volume were measured by Doppler echocardiography. We then calculated the ratio of LAD cross-sectional area to LV mass and the ratio of LAD flow volume to LV mass. In 12 patients with Kawasaki disease, LAD flow velocity and flow velocity integral were measured by Doppler echocardiography at the time of Doppler guide wire examination. There were significant correlations between echocardiographic and Doppler guide wire methods for flow velocity and flow velocity integral (r = 0.77 and 0.83, P <.01, respectively). The LAD flow velocity decreased significantly with age (r = -0.43, P <.01). The LAD flow volume per minute increased significantly with age (r = 0.55, P <.01). However, LAD flow volume/LV mass ratio in younger infants was high and decreased significantly with age (r = -0.66, P <.01). This study shows that LAD flow patterns can be reliably assessed by transthoracic Doppler echocardiography in the majority of pediatric subjects. In the current study, the LAD flow velocity and the ratio of LAD flow volume to LV mass in infants was high and decreased with age, suggesting high myocardial perfusion. High LAD peak velocity in infants may be related with high resting coronary flow. Age-related changes in the LAD flow characteristics must be taken into consideration in the study of the coronary circulation in children. PMID- 11781558 TI - A retrospective experience of right atrial and superior vena caval thrombi diagnosed by transesophageal echocardiography. AB - Central venous catheter (CVC) thrombosis and infection has become a frequent finding in immunosuppressed and chronically ill medical patients, particularly those with end-stage renal disease. Transesophageal echocardiography (TEE), as the only reliable noninvasive method of imaging the superior vena cava (SVC) is appreciated to be very useful in the evaluation of these lesions. We retrospectively review our findings of TEE for this purpose, with regard to frequency of positive findings, patient characteristics, and microbiologic findings from SVC and right atrial thrombi and vegetations associated with CVCs. PMID- 11781559 TI - Experience with an ultrasound stethoscope. AB - BACKGROUND: To test the diagnostic potential of the SonoHeart, a battery-powered hand-held ultrasound imaging device, in an outpatient clinic setting. METHODS: A total of 114 patients with a variety of cardiac diseases were examined by 2 independent cardiologists with the hand-held device using the standard echocardiographic system (SE) as a reference. Global right ventricular (RV) and left ventricular (LV) function (scored as normal, mildly to moderately, or severely reduced) and internal cavity dimensions were assessed. Regional wall motion of 6 segments using a 2-point score (1 = normal wall motion, 2 = abnormal wall motion) was evaluated in 34 patients on-line. RESULTS: There was a good agreement between the 2 imaging devices for evaluation of global LV (93%) and RV function (99%), regional wall motion (90%), dimensions of the LV (99%) and the RV (99%), and the left (96%) and right atria (99%). Furthermore, SonoHeart identified hypertrophic cardiomyopathy, pericardial effusion, and abnormalities of valves. CONCLUSION: The SonoHeart device allows rapid and accurate diagnosis, whenever needed in the outpatient clinic. PMID- 11781560 TI - Clinical and echocardiographic aspects of double-outlet left atrium. AB - Double outlet left atrium is a very rare complex atrial malformation. We present 3 cases of double outlet left atrium with 2 atrioventricular valves diagnosed by transthoracic and transesophageal echocardiography. PMID- 11781561 TI - Quadricuspid aortic valve abnormality associated with aortic stenosis and aortic insufficiency. AB - Quadricuspid aortic valve is a rare congenital malformation of the aortic valve. Transthoracic 2-dimensional echocardiography can delineate aortic valve and diagnose most quadricuspid aortic valves. This article is a report of a quadricuspid aortic valve associated with aortic stenosis and aortic insufficiency diagnosed by transthoracic echocardiography. PMID- 11781562 TI - Unusual cases of infective endocarditis. AB - We report 2 patients with unusual cases of infective endocarditis. The first patient had a large, mural vegetation on left ventricle that was diagnosed with transthoracic echocardiography; and the second patient had a large, mobile vegetation in the descending prosthetic aorta with an abscess cavity around the vessel, diagnosed by transesophageal echocardiography. This report confirms the usefulness of transthoracic and transesophageal echocardiography in the diagnosis and management of uncommon cases of endocarditis. PMID- 11781563 TI - Pseudoaneurysm of the mitral-aortic fibrosa: myocardial ischemia secondary to left coronary compression. AB - In the current study we describe the cases of 2 patients operated on for left sided endocarditis, who later had myocardial ischemia develop secondary to left coronary artery compression from a pseudoaneurysm of the mitral-aortic fibrosa. Because the symptoms of angina persisted despite medical treatment, both patients had second surgeries. Myocardial revascularization was performed in 1 patient; the other patient, who had a severely depressed ventricular function, was given an orthotopic cardiac transplant. PMID- 11781564 TI - Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase 1. AB - Excitotoxic brain lesions initially result in the primary destruction of brain parenchyma, after which microglial cells migrate towards the sites of injury. At these sites, the cells produce large quantities of oxygen radicals and cause secondary damage that accounts for most of the loss of brain function. Here we show that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, regulated by the nuclear enzyme poly(ADP ribose) polymerase-1 (PARP-1) through the formation of a nuclear PARP-NF-kappaB protein complex. Downregulation of PARP or CD11a by transfection with antisense DNA abrogated microglial migration almost completely and prevented neurons from secondary damage. PMID- 11781565 TI - Feedback regulation of the MBF transcription factor by cyclin Cig2. AB - The Mlu1-binding factor (MBF) from the fission yeast Schizosaccharomyces pombe contains the proteins Res1p and Res2p and binds to the Mlu1 cell-cycle box (MCB) element in DNA, activating the transcription of genes required for S phase. We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. Deletion of MCB elements in the cig2 promoter perturbed the expression not only of cig2 but also of other MBF-dependent genes, indicating that Cig2p could regulate MBF activity. Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle. PMID- 11781566 TI - MAP kinase dynamics in response to pheromones in budding yeast. AB - Although scaffolding is a major regulator of mitogen-activated protein kinase (MAPK) pathways, scaffolding proteins are poorly understood. During yeast mating, MAPK Fus3p is phosphorylated by MAPKK Ste7p, which is activated by MAPKKK Ste11p. This MAPK module interacts with the scaffold molecule Ste5p. Here we show that Ste11p and Ste7p were predominantly cytoplasmic proteins, while Ste5p and Fus3p were found in the nucleus and the cytoplasm. Ste5p, Ste7p and Fus3p also localized to tips of mating projections in pheromone-treated cells. Using fluorescence recovery after photobleaching (FRAP), we demonstrate that Fus3p rapidly shuttles between the nucleus and the cytoplasm independently of pheromones, Fus3p phosphorylation and Ste5p. Membrane-bound Ste5p can specifically recruit Fus3p and Ste7p to the cell cortex. Ste5p remains stably bound at the plasma membrane, unlike activated Fus3p, which dissociates from Ste5p and translocates to the nucleus. PMID- 11781567 TI - Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration. AB - Multicellular animal development depends on integrins. These adhesion receptors link to the actin cytoskeleton, transmitting biochemical signals and force during cell migration and interactions with the extracellular matrix. Many integrin cytoskeleton connections are formed by filamins and talin. The beta7 integrin tail binds strongly to filamin and supports less migration, fibronectin matrix assembly and focal adhesion formation than either the beta1D tail, which binds strongly to talin, or the beta1A tail, which binds modestly to both filamin and talin. To probe the role of filamin binding, we mapped the filamin-binding site of integrin tails and identified amino acid substitutions that led to selective loss of filamin binding to the beta7 tail and gain of filamin binding to the beta1A tail. These changes affected cell migration and membrane protrusions but not fibronectin matrix assembly or focal adhesion formation. Thus, tight filamin binding restricts integrin-dependent cell migration by inhibiting transient membrane protrusion and cell polarization. PMID- 11781568 TI - A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. AB - Asymmetric cell division requires the orientation of mitotic spindles along the cell-polarity axis. In Drosophila neuroblasts, this involves the interaction of the proteins Inscuteable (Insc) and Partner of inscuteable (Pins). We report here that a human Pins-related protein, called LGN, is instead essential for the assembly and organization of the mitotic spindle. LGN is cytoplasmic in interphase cells, but associates with the spindle poles during mitosis. Ectopic expression of LGN disrupts spindle-pole organization and chromosome segregation. Silencing of LGN expression by RNA interference also disrupts spindle-pole organization and prevents normal chromosome segregation. We found that LGN binds the nuclear mitotic apparatus protein NuMA, which tethers spindles at the poles, and that this interaction is required for the LGN phenotype. Anti-LGN antibodies and the LGN-binding domain of NuMA both trigger microtubule aster formation in mitotic Xenopus egg extracts, and the NuMA-binding domain of LGN blocks aster assembly in egg extracts treated with taxol. Thus, we have identified a mammalian Pins homologue as a key regulator of spindle organization during mitosis. PMID- 11781569 TI - Desmoplakin is essential in epidermal sheet formation. AB - We have generated an epidermis-specific desmoplakin (DP) mouse knockout, and show that epidermal integrity requires DP; mechanical stresses to DP-null skin cause intercellular separations. The number of epidermal desmosomes in DP-null skin is similar to wild type (WT), but they lack keratin filaments, which compromise their function. DP-null keratinocytes have few desmosomes in vitro, and are unable to undergo actin reorganization and membrane sealing during epithelial sheet formation. Adherens junctions are also reduced. In vitro, DP transgene expression rescues these defects. DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion. PMID- 11781570 TI - Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. AB - Although nuclear envelope (NE) assembly is known to require the GTPase Ran, the membrane fusion machinery involved is uncharacterized. NE assembly involves formation of a reticular network on chromatin, fusion of this network into a closed NE and subsequent expansion. Here we show that p97, an AAA-ATPase previously implicated in fusion of Golgi and transitional endoplasmic reticulum (ER) membranes together with the adaptor p47, has two discrete functions in NE assembly. Formation of a closed NE requires the p97-Ufd1-Npl4 complex, not previously implicated in membrane fusion. Subsequent NE growth involves a p97-p47 complex. This study provides the first insights into the molecular mechanisms and specificity of fusion events involved in NE formation. PMID- 11781571 TI - Import of adenovirus DNA involves the nuclear pore complex receptor CAN/Nup214 and histone H1. AB - Adenovirus type 2 (Ad2) imports its DNA genome through the nuclear pore complex (NPC) of cells in interphase for viral production. Here we identify the NPC filament protein CAN/Nup214 as a docking site for incoming Ad2 capsids. Binding to CAN is independent of cytosolic factors. Capsids disassemble at NPCs to free their DNA for import. This process requires binding of nuclear histone H1 to the stably docked capsids and involves H1-import factors, restricting this irreversible process to the proximity of the nucleus. Our results provide a molecular mechanism for disassembly of Ad2 and reveal an unexpected function of histone H1 in virus-mediated DNA import. PMID- 11781573 TI - Design and application of a cytokine-receptor-based interaction trap. AB - Ligand-induced clustering of type I cytokine receptor subunits leads to trans phosphorylation and activation of associated cytosolic janus kinases (JAKs). In turn, JAKs phosphorylate tyrosine residues in the receptor tails, leading to recruitment and activation of signalling molecules. Among these, signal transducers and activators of transcription (STATs) are important in the direct transmission of signals to the nucleus. Here, we show that incorporation of an interaction trap in a signalling-deficient receptor allows the identification of protein-protein interactions, using a STAT-dependent complementation assay. Mammalian protein-protein interaction trap (MAPPIT) adds to existing yeast two hybrid procedures, as originally explored by Fields and Song, and permits the detection of both modification-independent and of phosphorylation-dependent interactions in intact human cells. We also demonstrate that MAPPIT can be used to screen complex complementary DNA libraries, and using this approach, we identify cytokine-inducible SH2-containing protein (CIS) and suppressor of cytokine signalling-2 (SOCS-2) as interaction partners of the phosphotyrosine 402 (Tyr 402)-binding motif in the erythropoietin receptor (EpoR). Importantly, this approach places protein-protein interactions in their normal physiological context, and is especially applicable to the in situ analysis of signal transduction pathways. PMID- 11781572 TI - The GM130 and GRASP65 Golgi proteins cycle through and define a subdomain of the intermediate compartment. AB - Integrating the pleomorphic membranes of the intermediate compartment (IC) into the array of Golgi cisternae is a crucial step in membrane transport, but it is poorly understood. To gain insight into this step, we investigated the dynamics by which cis-Golgi matrix proteins such as GM130 and GRASP65 associate with, and incorporate, incoming IC elements. We found that GM130 and GRASP65 cycle via membranous tubules between the Golgi complex and a constellation of mobile structures that we call late IC stations. These stations are intermediate between the IC and the cis-Golgi in terms of composition, and they receive cargo from earlier IC elements and deliver it to the Golgi complex. Late IC elements are transient in nature and sensitive to fixatives; they are seen in only a fraction of fixed cells, whereas they are always visible in living cells. Finally, late IC stations undergo homotypic fusion and establish tubular connections between themselves and the Golgi. Overall, these features indicate that late IC stations mediate the transition between IC elements and the cis-Golgi face. PMID- 11781574 TI - Differential contribution of cytoplasmic Ca2+ and Ca2+ influx to gamete fusion and egg activation in maize. AB - In multicellular organisms, gamete fusion triggers a set of events, collectively known as egg activation, that leads to the development of a new individual. Every species that has been studied shows at least one rise in cytoplasmic Ca2+ concentration ([Ca2+]Cyt) after gamete fusion which is believed to be involved in activation. Yet the source and regulation of this Ca2+ signal and the way it is transduced inside the zygote are controversial. In higher plants, in vitro fertilization (IVF) has enabled the description of a rise in [Ca2+]Cyt (ref. 4) that is sufficient for activation, and of a Ca2+ influx that spreads as a wavefront from the fusion site The relationship between these two responses is unknown. Using a new combination of methods that simultaneously monitor the extracellular flux with a Ca2+-vibrating probe, and [Ca2+]Cyt by widefield imaging, we directly determined that the Ca2+ influx precedes the [Ca2+]Cyt elevation by 40-120 s. In addition, results from experiments using the Ca2+ channel inhibitor gadolinium (Gd3+) suggest that the Ca2+ influx may be necessary for sperm incorporation. We also present evidence for a putative sperm-dependent Gd3+-insensitive localized Ca2+ influx confined to the fusion point. PMID- 11781575 TI - The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling. AB - The PTEN tumour suppressor and pro-apoptotic gene is frequently mutated in human cancers. We show that PTEN transcription is upregulated by Egr-1 after irradiation in wild-type, but not egr-1-/-, mice in vivo. We found that Egr-1 specifically binds to the PTEN 5' untranslated region, which contains a functional GCGGCGGCG Egr-1-binding site. Inducing Egr-1 by exposing cells to ultraviolet light upregulates expression of PTEN messenger RNA and protein, and leads to apoptosis. egr-1-/- cells, which cannot upregulate PTEN expression after irradiation, are resistant to ultraviolet-light-induced apoptosis. Therefore, Egr 1 can directly regulate PTEN, triggering the initial step in this apoptotic pathway. Loss of Egr-1 expression, which often occurs in human cancers, could deregulate the PTEN gene and contribute to the radiation resistance of some cancer cells. PMID- 11781576 TI - Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. AB - The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin. Presenilin mediates transmembrane cleavage of single-pass transmembrane proteins with short extracellular domains, including the ligand-activated form of the receptor Notch and beta-amyloid precursor protein (beta-APP). Transmembrane cleavage of Notch is essential for signal transduction, and transmembrane cleavage of beta-APP generates pathogenic amyloid peptides implicated in Alzheimer's disease. Here, we investigate the requirement for Nicastrin in Presenilin-mediated transmembrane cleavage. We show that, in Drosophila, loss of Nicastrin activity blocks the accumulation of Presenilin associated with the apical plasma membrane, abolishes Presenilin-dependent cleavage of the transmembrane domains of Notch and beta-APP, and abrogates Notch signal transduction. PMID- 11781577 TI - Milestones in cell division. PMID- 11781578 TI - Welcome to the nucleus: CAN I take your coat? PMID- 11781579 TI - Mitochondrial fission in life and death. PMID- 11781580 TI - Deconstructing desmoplakin. PMID- 11781581 TI - Natural sunscreen revealed. PMID- 11781582 TI - The nuclear envelope: filling in gaps. PMID- 11781586 TI - The evolution of diverse biological responses to DNA damage: insights from yeast and p53. AB - The cellular response to ionizing radiation provides a conceptual framework for understanding how a yeast checkpoint system, designed to make binary decisions between arrest and cycling, evolved in a way as to allow reversible arrest, senescence or apoptosis in mammals. We propose that the diversity of responses to ionizing radiation in mammalian cells is possible because of the addition of a new regulatory control module involving the tumour-suppressor gene p53. We review the complex mechanisms controlling p53 activity and discuss how the p53 regulatory module enables cells to grow, arrest or die by integrating DNA damage checkpoint signals with the response to normal mitogenic signalling and the aberrant signalling engendered by oncogene activation. PMID- 11781587 TI - [Medical - Psychological Consultation at San Roque Hospital] AB - This paper has been done to comunicate a conception of Interconsultation (Liaison) developed in the Metal Health Service from San Roque Hospital. It begins with a general review around theoretical and technical evolution about Interconsultation in a general Hospital. Then it describes our theoretical point of view and its instrumentation, with especial enphasis in the idea of "to include the human being of our sick subject". The article affirms the necessity of thransferencial relantionship among Interconsultator and Interconsultant. All process is representated by diagrams. In them, we can see the identification of problems, the strategies and tactics that determine courses of action, and how to evaluate these procedures. PMID- 11781588 TI - ? PMID- 11781589 TI - ? PMID- 11781590 TI - ? PMID- 11781591 TI - [III Brazilian Guidelines on Dyslipidemias and Guideline of Atherosclerosis Prevention from Atherosclerosis Department of Sociedade Brasileira de Cardiologia]. PMID- 11781592 TI - Morphologic and morphometric evaluation of pancreatic islets in chronic Chagas' disease. AB - PURPOSE: Hyperglycemia and abnormal glucose tolerance tests observed in some patients with chronic Chagas' disease suggest the possibility of morphological changes in pancreatic islets and/or denervation. The purpose of this study was to describe the morphology and morphometry of pancreatic islets in chronic Chagas' disease. METHODS: Morphologic and computerized morphometric studies were performed in fragments of the head, body, and tail regions of the pancreas obtained at necropsies of 8 normal controls and 17 patients with chronic Chagas' disease: 8 with the digestive form (Megas) and 9 with the congestive heart failure form. RESULTS: The Megas group had a larger (p < 0.05) pancreatic islet area in the tail of the pancreas (10649.3 +/- 4408.8 micrometer2) than the normal control (9481.8 +/- 3242.4 micrometer2) and congestive heart failure (9475.1 +/- 2104.9 micrometer2) groups; likewise, the density of the pancreatic islets (PI) was greater (1.2 +/- 0.7 vs. 0.9 +/- 0.6 vs. 1.9 +/- 1.0 PI/mm2, respectively). In the tail region of the pancreas of patients with the Megas form, there was a significant and positive correlation (r = +0.73) between the area and density of pancreatic islets. Discrete fibrosis and leukocytic infiltrates were found in pancreatic ganglia and pancreatic islets of the patients with Chagas' disease. Trypanosoma cruzi nests were not observed in the examined sections. Individuals with the Megas form of Chagas' disease showed increased area and density of pancreatic islets in the tail of the pancreas. CONCLUSION: The observed morphometric and morphologic alterations are consistent with functional changes in the pancreas, including glycemia and insulin disturbances. PMID- 11781593 TI - Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency. AB - Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4) and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone. PMID- 11781594 TI - Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases. AB - INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion. PMID- 11781595 TI - Vancomycin monitoring in term newborns: comparison of peak and trough serum concentrations determined by high performance liquid chromatography and fluorescence polarization immunoassay. AB - INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower. PMID- 11781596 TI - Prostate carcinoma with neuroendocrine differentiation: case report and literature review. AB - Neuroendocrine differentiation in prostatic carcinomas generally confers a more aggressive clinical behavior and less favorable prognosis than usual prostatic carcinomas. In this manuscript, we report a case of a 58-year-old man with prostatic carcinoma who died 1 year after initial diagnosis. Autopsy showed a disseminated prostatic carcinoma with neuroendocrine differentiation. There were metastasis to the spleen, an organ infrequently involved by disseminated epithelial neoplasms. Neuroendocrine differentiation was demonstrated by immunohistochemical studies in the biopsy and autopsy material. PMID- 11781597 TI - Persistence of the embryonic lateral marginal vein: report of two cases. AB - PURPOSE: Congenital venous malformations of the lower limbs represent a particular challenge for the vascular surgeon. Persistence of fetal veins is a rare malformation, and the most common is the persistence of the lateral marginal vein usually observed in patients with Klippel-Trenaunnay Syndrome. The persistence of this embryonic vein as an isolated venous malformation without the other characteristics of the Klippel-Trenaunnay Syndrome has not yet been reported. This paper describes two cases. METHODS: Two patients, a 17-year-old male patient and a 16-year-old female, have had since their birth a large venous trunk in the lateral aspect of the right leg and thigh. The limbs underwent duplex scanning and phlebography. The surgical removal of the lateral marginal vein was performed. RESULTS: Surgical treatment resulted in very good functional and aesthetic results. Follow-up at 26 months showed no evidence of varicose vein recurrence. CONCLUSIONS: To achieve good results, surgical intervention may be indicated in cases of orthopedic deformity, hemorrhage, symptomatic, and unaesthetic lesions. PMID- 11781598 TI - Biological and genetic characteristics of uropathogenic Escherichia coli strains. AB - The aim of the present study was to determine biological characteristics such as expression of fimbriae, Congo red binding, production of hemolysin and aerobactin, adhesion to HeLa and uroepithelial cells and invasion of HeLa cells by Escherichia coli isolates obtained from patients showing clinical signs of urinary tract infection (UTI). Also, the presence of genes (apa, afa, spa) for fimbria expression and cytotoxic necrotizing factors (CNF1, CNF2) was assayed using specific primers in PCR. The data obtained were compared with the clonal relationships obtained by analysis of multilocus enzyme electrophoresis (MLEE), restriction fragment length polymorphism (RFLP) of the rDNA (ribotyping) and enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). All isolates but one presented a combination of at least two of the characteristics studied, a fact suggesting the presence of pathogenicity islands (PAIs). Diffuse adherence type to HeLa cells was observed to occur in most of the strains, but adhesion to uroepithelial cells seems to be a more reliable test to verify pathogenicity. Although four strains seemed to be able to invade HeLa cells when assayed by light microscopy, electron microscopy studies demonstrated that these strains were not invasive. MLEE, RFLP and ERIC-PCR were able to group the isolates differently into main clusters that were not correlated with the presence of pathogenic traits. PMID- 11781599 TI - Outbreak of influenza type A (H1N1) in Iporanga, Sao Paulo State, Brazil. AB - From June to July 1999 an outbreak of acute respiratory illness occurred in the town of Iporanga. Out of a total of 4,837 inhabitants, 324 cases were notified to the Regional Surveillance Service. Influenza virus was isolated from 57.1% of the collected samples and 100% seroconversion to influenza A (H1N1) was obtained in 20 paired sera tested. The isolates were related to the A/Bayern/07/95 strain (H1N1). The percentages of cases notified during the outbreak were 28.4%, 29.0%, 20.7%, 6.2% and 15.7% in the age groups of 0-4, 5-9, 10-14, 15-19 and older than 20 years, respectively. The highest proportion of positives was observed among children younger than 14 years and no cases were notified in people older than 65 years, none of whom had been recently vaccinated against influenza. These findings suggest a significant vaccine protection against A/Bayern/7/95, the H1 component included in the 1997-98 influenza vaccine for elderly people. This viral strain is antigenically and genetically related to A/Beijing/262/95, the H1 component of the 1999 vaccine. Vaccines containing A/Beijing/262/95 (H1N1) stimulated post-immunization hemagglutination inhibition antibodies equivalent in frequency and titre to both A/Beijing/262/95-like and A/Bayern/7/95-like viruses. Thus, this investigation demonstrates the effectiveness of vaccination against influenza virus in the elderly. PMID- 11781600 TI - Effectiveness of influenza vaccination in elderly outpatients in Sao Paulo city, Brazil. AB - To investigate the effectiveness of the influenza vaccine in a population of elderly outpatients, we compared the occurrence and frequency of influenza like illness (ILI), respiratory illness and hospitalization in vaccinated and non vaccinated subjects. All the outcomes were clinically defined. The two groups were similar with respect to demographics, health situation and habits. The influenza vaccine contributed to the protection of the elderly investigated, since the vaccinated subjects referred a significantly lower number of ILI than the non-vaccinated. There is a need for more studies about the effectiveness of the influenza vaccine in our country in elderly and other groups of our population. PMID- 11781601 TI - Detection of enteroviruses in cases of neurological disorders in the State of Para, Brazil. AB - Eighty-one cerebrospinal fluid (CSF) samples mainly from cases of aseptic meningitis and motor deficiency syndrome were sent to the Virology Section of Evandro Chagas Institute, Belem Para, in the period of January 1995 to January 1996 in order to isolate viruses. All samples were inoculated onto HEp-2 cell culture and newborn mice, with negative results. The probability of isolating viruses by these methods is reduced because of the low concentration of viral particles in these specimens. In order to obtain more information about the etiology of these cases, a group of 23 samples were selected to be tested by a more sensitive technique than the virus isolation - the reverse transcription polymerase chain reaction (RT-PCR). Specific primers directed to conserved regions in the enterovirus genome were used, considering that this group of viruses is frequently associated with these neurological disorder. The age of the patients ranged from 1 to 55 years and nearly all of them lived in Belem, State of Para, North of Brazil. Of 15 samples analyzed by RT PCR nine (60%) were positive; of these, 6 (66.6%) had motor deficiency and 3 (33.3%) developed aseptic meningitis. These results show that it is important to investigate enterovirus as cause of these syndromes. PMID- 11781602 TI - Serologic survey for hantavirus infections among wild animals in rural areas of Sao Paulo State, Brazil. AB - A serosurvey was conducted in wild animals captured close to two areas where hantavirus cardiopulmonary syndrome (HCPS) occurred in Sao Paulo State, Brazil. Serum samples from a total of 43 mammals were tested for antibodies reactive with Sin Nombre (SN) hantavirus using a strip immunoblot assay. RNAs from the blood clots of the positive samples were submitted to reverse transcriptase-polymerase chain reaction (RT-PCR). Two rodents of the genus Oligoryzomys were positive for hantavirus antibodies. These animals were captured in the Iguape region and represented 16.7% (2/12) of the sera from rodents and 100.0% (2/2) of the Oligoryzomys captured in that area. RT-PCR failed to amplify any viral cDNA. These results are in agreement with other data that suggest that members of this genus are important reservoirs of hantaviruses in Brazil. PMID- 11781603 TI - Snakebites by Bothrops spp in children in Campinas, Sao Paulo, Brazil. AB - From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04). PMID- 11781604 TI - Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B. AB - BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 +/- 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT. PMID- 11781605 TI - An indirect immunofluorescence assay to detect antibodies against St. Louis Encephalitis virus. AB - An in house indirect immmunofluorescence assay ( IFA ) in relation to neutralization (NT) reference test, was assessed as a fast and cheap method to carry out serological surveys for St. Louis Encephalitis virus (SLE). Sera obtained from 213 blood donors were analyzed by both tests. The prevalence of seropositivity obtained with IFA was lower than (30.98%) that observed on NT (41.78%). The relative specificity rate of IFA was 96.77% whereas its relative sensitivity rate was 69.66%. Kappa index showed a good correlation between both tests. The results indicate that neutralization assay is still the serological test with the highest sensitivity and specificity relative rates for detecting antibodies against SLE virus. Nevertheless, the IFA could be useful as an alternative test in order to learn the circulation of the Flavivirus genus in a certain area. PMID- 11781606 TI - Identification of Cryptosporidium spp. oocysts in fecal smears stained with Heidenhain's iron hematoxylin. AB - There is no paucity of methods for diagnosing Cryptosporidium spp. infection. The merits of immunoassays notwithstanding, microscopic identification of Cryptosporidium spp. oocysts in fecal samples remains an important diagnostic procedure. It owes the persistence of its use to such characteristics as dispensing with expensive equipment and kits, requiring only basic laboratory facilities, and having a low probability of false positive results when permanent slides are prepared, which can be re-examined in case of doubt. Cryptosporidium spp. oocysts can be readily identified in fecal smears prepared according to a regressive iron hematoxylin staining technique. The number of steps and their duration, as well as costs, were reduced to a minimum without loss of image quality and permanence of the preparations. PMID- 11781607 TI - Liver abscess caused by Ascaris lumbricoides: case report. AB - A case is reported of a woman who lived in a rural area with a chronic illness that consisted of weight loss and abdominal pain in the epigastrium and upper right quadrant. The initial diagnosis was a mass in the liver, which was later, demonstrated, both by direct and histological examination, to be an abscess caused by Ascaris lumbricoides. Eggs of Ascaris lumbricoides and abundant Charcot Leyden Crystals were found. PMID- 11781608 TI - Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling. AB - In this paper, we address methods of multivariate regression. We discuss the value of regression compared to matched pairs analysis, methods of coding variables, basic concepts of the Cox model and interpretation of results of the Cox model. We present methods of handling variables whose effect changes with time. We present methods to check the assumptions of the Cox regression. Finally, and perhaps most importantly, we provide suggestions for presenting the results in clear and thorough tables and graphs. PMID- 11781609 TI - Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation. AB - Published data suggest that the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment in children receiving busulfan as a conditioning agent for bone marrow transplantation (BMT). We previously found in children that a Bu Css <600 ng/ml correlated with autologous recovery/mixed chimerism; there was no correlation between Bu Css and regimen-related toxicity (RRT). In a cohort continuous with the previous trial, we prospectively evaluated targeted busulfan concentrations in 32 pediatric patients (age 0.6-18.5 years) with AML (n = 6), CML (n = 6) and non-malignant disorders (n = 20) receiving HLA closely matched donor grafts. In this trial, individual busulfan pharmacokinetics were performed prior to admission. Busulfan doses were then adjusted to achieve a Bu Css target range of 600-900 ng/ml +/- 10% depending on donor source and disease. A repeat study was done following dose 1 of the conditioning regimen. Thirty of thirty-two (94%) patients achieved target concentrations. Total busulfan doses ranged from 10.9 to 29 mg/kg. Thirty of thirty-two patients (94%) have durably engrafted. Grade 3/4 RRT occurred in seven patients (21%). Targeting Bu Css ranges of 600-900 ng/ml significantly improved our rate of successful engraftment from 74% to 94% (P = 0.043). These results indicate that targeted busulfan dosing optimizes allogeneic engraftment in children. PMID- 11781610 TI - Enumeration of bone marrow 'homing' haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation. AB - Expression of the chemokine receptor CXCR4 on human haemopoietic stem cells (HSC) may play a crucial role in localising these cells to the bone marrow. To evaluate whether CXCR4 expression is clinically relevant we have enumerated CXCR4-positive HSC used for allogeneic transplantation and sought any relationship with the rate of subsequent haemopoietic reconstitution. CD34-positive progenitor cells were isolated from peripheral blood stem cell (PBSC) collections from 16 normal donors. The proportion of cells co-expressing CXCR4 was enumerated and the times to recipient haemopoietic reconstitution measured. The median frequency of CD34 positive cells co-expressing CXCR4 was 41% (range 16% to 76%) and the median number of CXCR4 CD34 double-positive cells infused at transplantation was 2.5 x 10(6) cells/kg (range 0.8-10.3). Patients receiving >2.5 x 10(6) CXCR4 CD34 double-positive cells/kg demonstrated a significant shortening of time to platelet engraftment compared to the recipients of the lower cell doses (10 days vs 14.5 days, respectively, P = 0.02) with all but one of the recipients of the higher cell doses achieving platelet engraftment by day 11. Co-expression of CXCR4 on CD34-positive progenitor cells may be an important determinant of post transplant engraftment and in our hands transplantation of a minimum of 2.5 x 10(6) CXCR4 CD34 double-positive cells/kg ensured rapid post-transplant platelet recovery. PMID- 11781611 TI - High-dose chemotherapy and CD34-selected peripheral blood progenitor cell transplantation for patients with breast cancer metastatic to bone and/or bone marrow. AB - Fifty women with breast cancer metastatic to bone or bone marrow involvement on light microscopy at the time of initial evaluation were treated with high-dose chemotherapy (HDC) and peripheral blood progenitor cell (PBPC) transplantation with CD34(+) cell selection using the Isolex 300i system. All patients received induction chemotherapy. PBPC were mobilized with chemotherapy and granulocyte colony-stimulating factor. The median CD34(+) progenitor purity was 94.7% (range 72-98.7%) and recovery 38.4% (range 21-60%). Forty-eight hours after HDC with cyclophosphamide, cisplatin and carmustine, PBPC were reinfused. Median time to neutrophil count >0.5 x 10(9)/l was 9 (range 9-12) days and to platelet transfusion independence 11 (4-30) days. These data demonstrate that selected CD34(+) PBPCs allow rapid hematologic reconstitution after HDC. During follow-up, 23% of patients developed herpes zoster. Two patients developed cytomegalovirus infections. Three patients developed fungal infections. The development of these infections was not associated with steroid use but appeared more frequently in patients with diabetes mellitus. Seventy-four per cent of patients received steroids for pulmonary toxicity. Treatment-related mortality was 4%. Progression free survival and overall survival at 35 months was 22.4% and 40.5%, with a median of 11.4 months and 15.4 months, respectively. PMID- 11781612 TI - Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant. AB - Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age <18 and <2 organ toxicities were marginally predictive of better survival. We conclude that BMT from PMRD is a reasonable option for patients with refractory AML post autograft. PMID- 11781613 TI - Peripheral blood stem cell transplantation in children with beta-thalassemia. AB - Fifteen patients with beta-thalassemia received an allogeneic peripheral blood stem cell transplant. Median age was 3.5 years (1-15 years). Six were class I, four class II and five class III according to the Pesaro criteria. All of the donors were HLA-phenotypically identical (13 siblings and two parents). Nine patients were given BU + CY and six BU + CY plus ATG as conditioning. All patients received MTX (+1, +3, +6) and CsA (9-12 months) post transplant for GVHD prophylaxis. The median neutrophil and platelet engraftment times were day 12 and day 16, respectively. cGVHD was observed in three patients. Two patients died. Thirteen patients are well, and transfusion-independent 2-30 months after PSCT. No recurrences of thalassemia have been seen. Overall and event-free survival were 86.6%. In conclusion, we suggest that PSCT can be considered a safe and effective treatment for children with beta- thalassemia. PMID- 11781614 TI - Serum cholinesterase is an early and sensitive marker of graft-versus host disease (GVHD) and transplant-related mortality (TRM). AB - Serum cholinesterase (CHE) has been reported to be a significant indicator of liver function and prognosis in patients with cirrhosis. On the other hand, liver complications are frequent following allogeneic stem cell transplantation (HSCT). We therefore tested whether CHE was predictive of graft-versus-host disease and outcome in HSCT recipients. We studied 689 patients receiving a HSCT from an HLA identical sibling (SIB) (n = 511), an alternative donor (n = 173) or a syngeneic twin (n = 5). Acute graft-versus-host disease (GVHD) was scored as 0-I, II, III IV in 325 (47%), 279 (41%), and 85 patients (12%) respectively; 190 (28%) patients died of transplant-related complications (TRM). On day -7 the median CHE serum level was comparable in patients who either survived or died of TRM (5900 IU/l). On day 0, serum CHE levels were respectively 2310 and 2120 IU/l (P = NS) indicating the impact of the conditioning regimen. On day +7 after HSCT, the median level for surviving patients was 2598 IU/l vs 2309 IU/l for patients who subsequently died (P = 0.0002), on day +21 CHE levels were respectively 3348 vs 2528 IU/l (P < 0.00001), on day +50, 3575 vs 2358 IU/l (P < 0.00001) and on day +100 4193 vs 2729 IU/l (P < 0.00001). CHE levels on day +50 strongly correlated with aGVHD (3803 vs 3070 vs 1933 IU/l for patients with GVHD grade 0-I, II, and III-IV, respectively (P < 0.00001) and relapse (3569 for patients relapsing vs 3115 IU/l for patients not relapsing, P = 0.0006). In conclusion, (1) serum cholinesterase is a simple and reliable marker of acute GVHD and transplant related complications; and (2) high CHE levels on day +50 predict relapse. If confirmed, the latter patients may be eligible for early reduction of immunosuppressive therapy. PMID- 11781615 TI - Clinical importance of confirming or excluding the diagnosis of chronic graft versus-host disease. AB - Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation. The presentation of this disease is varied, and it requires histological confirmation for diagnosis. In addition, cGVHD can often mimic other diseases, and vice versa. We have conducted a retrospective analysis of 123 patients referred to the GVHD clinic at the Johns Hopkins Oncology Center from 1994 to 1998 with a diagnosis of active cGVHD. Of these, nine patients (7%) had no evidence of cGVHD, and 25 patients (20%) had inactive cGVHD. Many of these patients were found to have other processes accounting for their ongoing symptoms. We conclude that since the therapy for this disease has significant toxicities and since what appears to represent cGVHD may actually be another disease, correct diagnosis of cGVHD or exclusion of this diagnosis is essential. PMID- 11781616 TI - Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT. AB - Late CMV disease remains a major concern in allogeneic BMT recipients. Few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. We evaluated the occurrence of antigenemia (AG) recurrences until day +365 in 76 patients who received pre-emptive ganciclovir (GCV) therapy prompted by AG > or = 2 positive cells. Sixty-two episodes of AG recurrences were detected in 33 of the 52 patients who had positive AG. Survival analysis showed a 45.4% probability of AG recurrence on day +100, 64.8% on day +180 and 71.2% on day +365. The median time for AG recurrences was 113 (35 to 343) days. Thirty-five of the 62 episodes (56.4%) occurred after day +100. More than 70% of the patients responded to a 2-week course of GCV and no CMV disease was observed shortly after discontinuation of GCV. The Cox proportional model showed a significant effect of AG recurrences on patient's follow-up only when the patient developed chronic GVHD (P = 0.012). Extended surveillance favored early introduction of GCV and late CMV pneumonia occurred in only one of the 76 patients (1.3%). AG recurrences are frequent after day +100 and extended surveillance until day +365 is recommended for patients who develop chronic GvHD. PMID- 11781617 TI - Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support. AB - Considerable progress has been made in improving the control of chemotherapy induced emesis. The impact of available antiemetic options for patients receiving stem cell transplants is unclear, as few prospective data have been collected. We prospectively evaluated antiemetic outcome in patients receiving stem cell transplantation over a 7-day period following the initiation of chemotherapy. The primary endpoints were the number of emetic episodes and the extent of nausea measured on a four-point scale. Eighty-two patients were evaluated. Ninety-five percent of patients had nausea during the first week of treatment; 80% had at least one emetic episode. The percentage of patients with emesis was as follows: day 1: 13%, day 2: 21%, day 3: 30%, day 4: 38%, day 5: 44%, day 6: 39%, day 7: 18%. In multivariate analysis, gender, emesis with prior chemotherapy, history of morning or motion sickness, type of transplant (auto vs allo), use of total body irradiation, or use of dexamethasone did not effect emesis control. Most patients receiving high-dose chemotherapy experience incompletely controlled emesis. Control of nausea and emesis progressively worsened with each subsequent day following initiation of chemotherapy, reaching a nadir on day 5. New treatment approaches are needed to improve emesis control in this patient population. PMID- 11781618 TI - Double lumen port access in patients receiving allogeneic blood stem cell transplantation. AB - We performed a prospective trial investigating the feasibility of a double lumen port access in 26 patients with hematological malignancies or solid tumors receiving either standard conditioning (n = 9, median age 49 years (range 19-65)) or dose-reduced conditioning (n = 17, median age 56 years (range 35-66)) followed by allogeneic blood stem cell transplantation. The port system was implanted within 3 months (n = 20, range 7-91 days) before transplantation or as indicated at different time points after transplantation (n = 6, range 28-680 days). Most infusions, including the graft itself and all blood drawings, were performed via the port. Over a cumulative duration of 5622 days (1310 days after standard conditioning (range 56-349) and 4431 days after dose-reduced conditioning (range 49-489)) two port systems of patients receiving standard conditioning were removed due to early postimplantation pocket infection on day 6 and 8 after insertion, respectively. In the dose-reduced conditioning group only one late removal (day 287) of a port was required. Most of the patients in both groups reported less pain and a higher degree of comfort compared to peripheral or central venipuncture. The use of double lumen port access during conditioning and in an outpatient setting after allogeneic hemopoietic stem cell transplantation is feasible and advantageous for both patient and medical staff. Implantation several weeks before the start of conditioning might help in avoiding early infectious complications after conventional myeloablative conditioning. PMID- 11781619 TI - Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts. AB - Currently, bone marrow (BM), cord blood (CB), and G-CSF-mobilized peripheral blood progenitor cells (PBPCs) are the most commonly used sources for allogeneic stem cell transplantation (SCT). The aim of this study was to assess the yields and distribution of lymphocyte subsets, lymphocyte progenitors and hematopoietic stem cells (HSC) in each type of allograft by three-color flow cytometry. The yields of CD34(+)CD38(-) HSCs did not differ significantly between BM grafts (2.80 +/- 0.74 x 10(6)) and leukapheresis products (LPs) (1.82 +/- 0.64 x 10(6)), and were lowest in CB grafts (0.21 +/- 0.05 x 10(6)). For most lymphocyte subsets yields were lowest in CB grafts and significantly higher in LPs than in BM grafts. BM grafts, however, contained the highest yields of CD34(+)CD19(+)CD20(-) B cell progenitors and CD19(+)CD20(-) B cells. The relative frequencies of the naive CD45RA(+)CD45RO(-) phenotype among CD4(+) and CD8(high) T cells were highest in CB grafts (P < or = 0.001), and higher in LPs than in BM grafts (P < or = 0.02). The latter finding was in accordance with a preferential G-CSF mobilization of naive T cells relative to the total lymphocyte population (P < or = 0.014). CD3(+)CD8(low) and CD3(+)CD8(low)CD4(-) subsets, which facilitate engraftment in murine transplantation models, demonstrated a tendency towards lower frequencies among T cells in CB grafts and LPs compared to BM grafts. This observation coincided with a significantly reduced mobilization of subsets potentially enriched for facilitating cells as compared to the total lymphocyte population (P < or = 0.036). The CD34(+) compartment of CB grafts contained a significantly higher percentage (12.1%) of CD34(+)CD7(+)CD3(-) T cell progenitors than those of BM grafts (5.1%) and LPs (3.6%). In addition, CB lymphocytes contained the highest fraction of CD3(-)CD16/56(+) NK cells (P < or = 0.013) and almost no CD3(+)CD16/56(+) NKT cells (P < 0.001) compared to adult cell sources. In summary, LPs, CB allografts and BM allografts differ widely with respect to the cellular composition of their lymphocyte compartments, which is partially affected by a varying mobilization efficiency of G-CSF for distinct lymphocyte subsets. PMID- 11781620 TI - Intensive chemotherapy for progressive chronic lymphocytic leukemia administered early after a nonmyeloablative allograft. AB - A 51-year-old patient with refractory CLL elected to participate in a trial of nonmyeloablative trans- plantation from an HLA-matched unrelated donor. He received low-dose fludarabine/TBI, with infusion of donor PBPC and cyclosporin (CsA)/MMF. Early post transplant he experienced explosive tumor growth with respiratory insufficiency. After immunosuppression discontinuation and rituximab administration, no response was observed. This prompted treatment with cyclophosphamide (2 g/m(2)/day x 2), paclitaxel (250 mg/m(2) over 24 h), doxorubicin (50 mg/m(2)), solumedrol (500 mg/day), and a second dose of rituximab, from days +11 to +14. A rapid response was achieved. Chemotherapy did not cause an obvious compromise of donor stem cell engraftment or establishment of stable donor chimerism. PMID- 11781621 TI - Influence of transplantation regimen on prognostic significance of high-level minimal residual disease before allogeneic stem cell transplantation in children with ALL. AB - High MRD levels before transplantation in children receiving T cell-depleted unrelated grafts for relapsed ALL were associated with a 100% relapse risk. We report on two children with relapsed ALL who underwent non T cell-depleted BMT from unrelated donors. Despite a high residual tumor load pre- transplant and the occurrence of only aGVHD grade I, they are still in second complete remission 2.7 and 5.2 years after transplantation, respectively. Thus, we propose that the transplant regimens influence the prognostic significance of high MRD levels pre BMT. PMID- 11781622 TI - Lactoferrin for gut GVHD. PMID- 11781623 TI - Controversy in multiple myeloma transplants: tandem autotransplants and mini allografts. AB - Autologous stem cell transplantation appears to enhance outcome in multiple myeloma patients. To improve upon these results, various groups have utilized tandem autografts, as well as used reduced-conditioning allogeneic stem cell transplantation. These two approaches, discussed herein, have been promising. Inherent patient selection, however, appears to play a role and much of the data have not yet been subjected to peer-review scrutiny. At present, these strategies remain investigational and cannot be considered the standard-of-care for multiple myeloma patients. PMID- 11781624 TI - The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning. AB - The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD. PMID- 11781626 TI - Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients. AB - Tacrolimus is an immunosuppressant commonly used in the prevention of graft versus-host disease (GVHD) following allogeneic HCT. Unfortunately, the use of tacrolimus is associated with variable immunosuppression and toxicity. The purpose of this study was to describe tacrolimus population pharmacokinetic parameters, to identify relationships between clinical covariates and pharmacokinetic estimates, and to develop a model to predict tacrolimus clearance in HCT patients. Steady-state whole blood tacrolimus concentrations (n = 1625) obtained during intravenous and oral therapy were analyzed in 122 patients. Population clearance (CL) was 5.22 l/h and bioavailability (F) was 0.28. The influence of clinical covariates on population estimates of CL and F of tacrolimus were tested with nonlinear mixed effects models (NONMEM). CL was significantly reduced by elevations in total bilirubin 2.0-9.9 mg/dl (CL * 0.797), bilirubin > or = 10 mg/dl (CL * 0.581), serum creatinine > or = 2 mg/dl (CL * 0.587), grade III/IV graft-versus-host disease (CL * 0.814) and veno occlusive disease (CL 0.814). No covariates were predictive of oral F. The interindividual variabilities in CL and F were 33% and 44%, respectively. Residual variability was 27.5% and 16.8% at tacrolimus concentrations of 10 microg/l and 20 microg/l, respectively. These models may be used to predict tacrolimus clearance and doses in adult patients following HCT. PMID- 11781625 TI - Improved clinical outcome of paediatric bone marrow recipients using a test dose and Bayesian pharmacokinetic individualization of busulfan dosage regimens. AB - In order to control busulfan pharmacokinetic variability and toxicity, a specific monitoring protocol was instituted in our bone marrow transplant BMT paediatric patients including a test dose, daily Bayesian forecasting of busulfan plasma levels, and Bayesian individualization of busulfan dosage regimens. Twenty-nine children received BMT after a busulfan-based conditioning regimen. Individual pharmacokinetic parameters were obtained following a 0.5 mg*kg test dose and were used for daily individualization of dosage regimens during the subsequent 4-day course of treatment. Doses were adjusted to reach a target mean AUC per 6 h between 4 and 6 microg.h.ml(+1). Plasma busulfan assays were performed by liquid chromatography. Pharmacokinetic analysis used the USC*PACK software. The performance of the test dose to predict AUC during the busulfan regimen was evaluated. Incidence of toxicity, chimerism and relapse, overall Kaplan-Meier survival, and VOD-free survival were compared after matching our patients (group A) with patients conditioned by using standard doses of busulfan (group B). Busulfan doses were decreased in 69% of patients compared to conventional doses. Expected AUC was significantly correlated with observed AUC and predictability of the test dose was 101.9 +/- 17.9%. Incidence of VOD in group A was 3.4% vs 24.1% in group B, while the incidence of stomatitis was similar. Engraftment was successful in all patients in group A. The rate of full engraftment at 3 months post-BMT was higher in group A (P = 0.012). Long-term overall survival did not differ between the two groups, in contrast to the 90-day survival. VOD-free survival was higher in group A (P = 0.026). Pharmacokinetic monitoring and individualization of busulfan dosage regimen are useful in improving clinical outcome and reducing early mortality in paediatric bone marrow transplant recipients. PMID- 11781627 TI - Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study. AB - Infections with the paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can result in serious morbidity and mortality after haemopoietic stem cell transplant (HSCT). Once pneumonia develops, the outcome of these infections is often poor despite anti-viral therapy. Aerosolised ribavirin has been evaluated as pre-emptive therapy for post-transplant RSV infections with some success. Due to the financial and logistic burden involved with the use of aerosolised ribavirin, we explored the efficacy and toxicity of oral ribavirin for pre-emptive therapy of post-transplant RSV and PIV infections in a dose escalating schedule (15-60 mg/kg/day). Five episodes each of RSV and PIV were treated in seven patients. Five patients were receiving treatment for GVHD and two acquired the infection in the pre-engraftment period. All the episodes of RSV infection improved with oral ribavirin with dose escalation to 30-45 mg/kg in three of them. On the other hand, only two of the five PIV infections improved with oral ribavirin. Of the three non-responders, two infections were acquired in the pre-engraftment period with one death from PIV pneumonia. Reversible anaemia was the only side-effect noted in patients treated for over 2 weeks. Thus, the use of oral ribavirin was well tolerated in the post-transplant period with no untoward toxicities. There was a trend towards better response in RSV infections, which needs to be further explored in controlled studies. PMID- 11781628 TI - CMV monitoring after peripheral blood stem cell and bone marrow transplantation by pp65 antigen and quantitative PCR. AB - We prospectively monitored 74 consecutive allogeneic and 50 autologous patients after bone marrow/stem cell transplantation from May 1999 to October 2000 at our institution with quantitative CMV PCR and pp65 antigen assay once weekly from conditioning therapy to days 120 and 80 after transplantation, respectively. Written informed consent was obtained from every patient. CMV prophylaxis consisted of acyclovir during transplant. Additionally all patients received only platelet products from CMV-negative donors. In the case of CMV infection preemptive therapy with gancyclovir was applied. In the case of CMV disease high dose immunoglobulin was given as well. In the allogeneic setting 16 out of 74 (22%) patients developed a positive PCR. Seven episodes of a positive pp65 antigen assay occurred in six allograft recipients. In the autologous setting no positive assay was found during the whole observation period. Additionally, in 6/16 patients a lymphoproliferative assay was performed during CMV infection. Two patients showed a positive (15 and 5.4) and four a negative (2,1.6,1,1.8) stimulation index. PMID- 11781629 TI - Oral eicosapentaenoic acid for complications of bone marrow transplantation. AB - The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome. PMID- 11781630 TI - Antibody responses to vaccinations given within the first two years after transplant are similar between autologous peripheral blood stem cell and bone marrow transplant recipients. AB - As a consequence of the significantly larger inoculum of lymphoid cells present in peripheral blood stem cell (PBSC) harvests compared to bone marrow (BM), it is possible that autoPBSCT recipients may have an earlier and*or enhanced response to vaccines. Until data to confirm this become available, the European Blood and Marrow Transplantation Association (EBMT) recommend that all transplant recipients be immunized in the same way regardless of stem cell source. We performed a prospective study comparing serological responses to influenza, pneumococcal polysaccharide and tetanus toxoid vaccines between autoPBSCT with autoBMT recipients. Antibody responses in sibling HLA-matched allogeneic BMT (alloBMT) survivors were also evaluated. All vaccines were administered within the first 2 years after stem cell transplantation. Fifty patients were enrolled. The time of vaccination after transplant was similar between autoPBSCT (mean 11 months for each vaccine) and autoBMT recipients (mean 12 months except 13 months for tetanus toxoid) (P = NS). Serological responses were poor and no significant difference in response to any of the vaccines used was seen between the three transplant cohorts. We provide no evidence that current EBMT guidelines be modified. Large prospective vaccine studies are needed to address the issue more fully. PMID- 11781631 TI - Successful non-myeloablative stem cell transplantation for a heavily transfused woman with severe aplastic anemia complicated by heart failure. AB - A 30-year-old Japanese woman weighing 35 kg with severe hemochromatosis due to multiple transfusions was referred to our clinic for treatment of severe aplastic anemia (SAA). The patient had heart failure with an ejection fraction of 36% requiring diuretics and a severe liver dysfunction with an indocyanine green clearance rate of 18%, as well as other transfusion-related complications such as chronic hepatitis due to hepatitis C virus and diabetes mellitus. She was treated with a non-myeloablative preparative regimen that included fludarabine monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-matched sister. The regimen was well tolerated, and engraftment rapidly occurred without any therapy-related complications. Chimerism analysis on day 14 after transplant showed reconstitution with 100% donor cells. She no longer needed transfusion after day 23 and has been well in 90% Karnofsky status at 4 months post transplant. The clinical course of this patient indicates that this preparative regimen enables SAA patients with severe organ failure to safely undergo allogeneic stem cell transplantation. PMID- 11781632 TI - Testicular germ cell tumor with rhabdomyosarcoma successfully treated by disease adapted chemotherapy including high-dose chemotherapy: case report and review of the literature. AB - Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified autologous PBSCT (APBSCT) and pamidronate. To date, remission has lasted for 4 years. Tumor adapted CHT including HD-CHT with APBSCT can induce long term remissions in high risk patients with transformed GCT. A review of the literature is given. PMID- 11781633 TI - Remission of severe, intractable autoimmune haemolytic anaemia following matched unrelated donor transplantation. AB - Immune-mediated haemolytic anaemia presenting post allogeneic bone marrow transplantation is often alloimmune in origin due to ABO or minor red cell incompatibilities. Autoimmune haemolytic anaemia is also recognised, is frequently difficult to treat and overall prognosis is often poor, usually from associated problems. Here, we present a case report of autoimmune haemolysis presenting in an 8-year-old boy 6 months post allogeneic bone marrow transplant requiring 4 years of immunosuppressive therapy before remission of haemolysis. This case report highlights the fact that it is possible for haemolysis to resolve post transplant even after years of immunosuppressive therapy. PMID- 11781634 TI - Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigen pulsed donor lymphocytes. AB - Allogeneic cell-mediated immunotherapy with donor lymphocyte infusion (DLI) can successfully reverse chemoradiotherapy-resistant relapse in patients with chronic myeloid leukemia treated by allogeneic bone marrow transplantation (BMT). We describe the first successful attempt in 1992 to treat DLI-resistant relapse in a patient with CML in full hematologic relapse, using immunized donor lymphocytes. Donor lymphocytes were pulsed in vitro with a mixture of irradiated peripheral blood lymphocytes (PBL) obtained from both parents, in order to trigger alloactivation of donor lymphocytes against host alloantigens presented by parental cells, using as stimulating cells maternal PBL expressing the shared maternal haplotype and paternal PBL expressing the shared paternal haplotype of the patient. Full hematologic, cytogenetic and molecular remission was induced for the first time, independently of GVH, and has persisted for more than 9 years. To the best of our knowledge, this report represents the first successful immunotherapy with donor lymphocytes activated against host-type antigens. We suggest that immune donor PBL may be superior to DLI, possibly effective even when all other modalities fail, perhaps even independently of GVHD. PMID- 11781635 TI - Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient. AB - A 45-year-old matched unrelated BMT recipient had sequential mucocutaneous herpes simplex virus (HSV) type 2 infections. Five months after BMT, a penile lesion occurred and was cured using acyclovir, as expected from in vitro susceptibility results. The same lesion recurred 1 month later but worsened with acyclovir. The HSV isolate was resistant to acyclovir (IC(50) = 105 microM), and a nucleotide (G) was added to the thymidine kinase gene leading to a premature stop codon. The lesion improved markedly with foscarnet. During this treatment a second HSV infection occurred on the buttocks 2 weeks after the first one and healed completely with acyclovir. This course correlated with in vitro results of the buttock HSV isolate which was foscarnet-resistant (IC(50) = 300 microg/ml) and acyclovir-sensitive. Surprisingly, no mutation gene of the foscarnet-resistant isolate was detected in the DNA polymerase gene. This case shows that an HSV acyclovir-resistant infection may be followed by an acyclovir-sensitive one. Determination of antiviral susceptibility is needed to monitor the treatment of various HSV infections in immunocompromised BMT recipients. PMID- 11781636 TI - Platelet glycoprotein complex Ia/IIa antibodies cause neonatal alloimmune thrombocytopenia but do not inhibit megakaryopoiesis and platelet recovery after allogeneic cord blood stem cell transplantation. AB - A sibling cord blood (CB) transplantation was performed in a boy with Wiskott Aldrich syndrome. The CB (31 x 10(6) CD34(+) cells) derived from a newborn sister with neonatal alloimmune thrombocytopenia (NAIT) with 40,000 platelets/microl, caused by a maternal anti-HPA-5b and HLA-A2 antibody. Maternal serum did not inhibit clonogenicity after in vitro testing of megakaryopoiesis. Accordingly, this CB was accepted for sibling transplantation. The transplantation showed a good course with fast and sustained hematopoietic reconstitution (granulocytes >500/microl on day +16, platelets >50,000/microl on day +30). This case demonstrates a successful CB transplantation from a donor suffering from NAIT. PMID- 11781637 TI - Intraoral psoralen ultraviolet A irradiation (PUVA) treatment of refractory oral chronic graft-versus-host disease following allogeneic stem cell transplantation. PMID- 11781638 TI - Lymphoproliferative disorder presenting as pulmonary nodules after bone marrow transplantation. PMID- 11781639 TI - Gemtuzumab Ozogamicin (Mylotarg) and hepatic veno-occlusive disease: take two acetaminophen, and... PMID- 11781640 TI - Stem cell transplantation for mantle cell lymphoma: should it ever be used outside clinical trials? AB - The outlook for patients with mantle cell lymphoma is poor. The reported median survival in most published series is only 3 to 4 years, and even the most favorable prognostic groups have median survival rates of only 5 years, with no evidence of cure. The use of autologous and allogeneic stem cell transplantation in this disease has increased dramatically in recent years. Despite encouraging reports from single centers and registries, the impact of stem cell transplantation on the outcome for mantle cell lymphoma is unclear. Optimal first line regimens for mantle cell lymphoma have yet to be defined, and it is therefore difficult to place the role of first remission transplantation in an appropriate context. Prospective randomized trials have been difficult to design and conduct in the absence of a well-defined 'standard' treatment. The role of stem cell transplantation as a salvage strategy is also unknown, although available data suggest that it does not improve survival in heavily pre-treated patients. In the absence of clear evidence for a survival advantage for patients receiving stem cell transplants for mantle cell lymphoma, entry into clinical trials should be a priority. PMID- 11781641 TI - Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation. AB - Busulfan pharmacokinetic parameters are useful in predicting the outcome of allogeneic bone marrow transplantation (BMT). Standard pharmacokinetic measurements require multiple blood samples. Various limited sampling models (LSM) have been proposed for reducing the sample number required for these measurements, essentially for patients with malignant disorders undergoing BMT. This study was undertaken to evaluate the existing LSM for busulfan pharmacokinetics to find out the most suitable method for patients with thalassaemia major undergoing BMT. Busulfan levels in plasma samples were analysed by HPLC. The AUC calculated by non-compartmental analysis using the program 'TOPFIT' was compared with previously published LSMs. Our seven sample pharmacokinetic data for AUC calculation was compared with the published LSMs. The three sample models suggested by Chattergoon et al and Schuler et al showed significant agreement with AUC TOPFIT (R(2) = 0.98 and 0.94, respectively) in our clinical context. Other models resulted in significant over or under representation of observed values (Vassal's model R(2) = 0.61; Chattergoon's two sample model R(2) = 0.84; four sample model R(2) = 0.83; Schuler's two sample model R(2) = 0.79). By these data the three sample LSM proposed by Chattergoon et al and Schuler et al are suitable for calculation of the AUC in patients with thalassaemia major undergoing BMT conditioned with oral busulfan. PMID- 11781642 TI - Excessive T cell depletion of peripheral blood stem cells has an adverse effect upon outcome following allogeneic stem cell transplantation. AB - We evaluated the outcome of two modes of T cell depletion for HLA-identical sibling stem cell transplants in 34 consecutive adult patients: group A (n = 11) received PBSC post CliniMACs immuno-magnetic enrichment of CD34(+) cells and group B (n = 23) received bone marrow following in vitro incubation with CAMPATH 1M and complement. All patients received an identical conditioning regimen which consisted of in vivoCAMPATH-1H 20 mg over 5 days, thiotepa 10 mg/kg, cyclophosphamide 120 mg/kg and 14.4 Gy TBI. No additional graft-versus-host disease prophylaxis was given. The mean T cell dose administered was 0.02 +/- 0.05 x 10(6)/kg for group A and 2.8 +/- 2.8 10(6)/kg for group B (P < 0.001). With a median follow-up of 28 months overall survival was 36.4% for group A at 12 months compared to 78.3% for group B (P = 0.001). Transplant-related mortality in group A at 12 months was 63.6% as compared to 18.0% in group B (P = 0.003). Most of the procedure-related deaths in group A occurred secondary to infection. These results suggest that extensive in vitro T cell depletion of peripheral blood stem cells in combination with in vivo T cell depletion may have profound effects upon the incidence of infections following allogeneic stem cell transplantation and this may adversely effect transplant-related mortality. PMID- 11781643 TI - DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma. AB - DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high dose programs for multiple myeloma. PMID- 11781644 TI - Allogeneic transplantation for multiple myeloma: further evidence for a GVHD associated graft-versus-myeloma effect. AB - We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median follow-up period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P = 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P = 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect. PMID- 11781645 TI - High-dose therapy in patients with Hodgkin's disease: the use of selected CD34(+) cells is as safe as unmanipulated peripheral blood progenitor cells. AB - Register data suggest that patients with Hodgkin's disease (HD) given high-dose therapy (HDT) with peripheral blood progenitor cells (PBPC) have a less favourable prognosis as compared to those given bone marrow as stem cell support. Since this can be due to infusion of tumour cells contaminating the PBPC grafts, we initiated a feasibility study in which PBPC grafts from HD patients were purged by CD34(+) cell enrichment. Controversy exists about whether the use of CD34(+) enriched stem cells leads to a delayed haematological and immune reconstitution. We compared these parameters, including risk of infections and clinical outcome after HDT, in patients with HD given either selected CD34(+) cells or unmanipulated PBPC as stem cell support. From October 1994 to May 2000, 40 HD patients with primary refractory disease or relapse were treated with HDT and supported with either selected CD34(+) cells (n = 21) or unmanipulated PBPC (n = 19) as stem cell support. All patients had chemosensitive disease at the time of transplantation. A median of 5.8 (range 2.7-20.0) vs 4.5 (range 2.3-17.6) x 10(6) CD34(+) cells per kilo were reinfused in the CD34(+) group and PBPC group, respectively. No difference was observed between the two groups with regard to time to haematological engraftment, reconstitution of B cells, CD56(+) cells and T cells at 3 and 12 months and infectious episodes after HDT. Two (5%) treatment-related deaths, one in each group, were observed. The overall survival at 4 years was 86% for the CD34(+)group and 74% for the PBPC group with a median follow-up of 37 months (range 1-61) and 46 months (range 4-82), respectively (P = 0.9). The results of this study demonstrate that the use of CD34(+) cells is safe and has no adverse effects either with respect to haematological, immune reconstitution or to infections after HDT. PMID- 11781646 TI - Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer. AB - This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m(2) over 96 h (days -12 to -8), etoposide 700 mg/m(2) every day x3 (days -6 to -4), and cyclophosphamide 4.2 g/m(2) on d -3 was followed by stem cells and granulocyte colony-stimulating factor. The median days of granulocyte count <500/microl was 14 (range 10-42) and platelets <20,000/microl was 13 (range 2-80). Median numbers of red cell and platelet transfusions were 15 (5-16) and 14 (4-103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values <50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0-56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1-68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal. PMID- 11781647 TI - Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer. AB - Early absolute lymphocyte count (ALC) recovery at day 15 post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival in multiple myeloma and non-Hodgkin's lymphoma. The relationship of ALC with clinical outcomes in metastatic breast cancer is unknown. We evaluated all 29 patients with metastatic breast cancer who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, from 1994 to 1999. The ALC threshold was set at 500 cells/microl on day 15 post-ASCT based on previous experience with hematologic malignancies. All patients were followed for a minimum of 2 years or until death, with a median follow-up for living patients of 2.25 years. Of the 29 patients, 17 have died with disease progression, two are alive and have progressed, and 10 are alive without progression. The median overall and progression-free survival times were significantly better for the 20 patients with ALC > or = 500 cells/microl compared with the nine patients with ALC <500 cells/microl (not reached vs 14 months, P < 0.0001; 24 vs 7 months, P < 0.0015, respectively). In conclusion, ALC > or = 500 cells/microl on day 15 post-ASCT was associated with significantly better survival in patients with metastatic breast cancer, suggesting the importance of early immune recovery post-ASCT in these patients. PMID- 11781648 TI - Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. AB - Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non susceptible Candida species was seen. PMID- 11781649 TI - Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections. AB - Pre-emptive antiviral therapy for CMV infection following allogeneic stem cell transplantation is an effective strategy for preventing CMV disease. This entails the logistic difficulty of daily intravenous therapy with ganciclovir or foscarnet to clinically asymptomatic patients. Cidofovir (CDV) is effective against CMV in vitro and has the practical advantage of weekly administration. However, there are limited data on the pre-emptive use of CDV in CMV infections. We carried out a pilot study exploring the efficacy and toxicity of CDV as primary pre-emptive therapy for CMV infections monitored by PCR-based assays. CDV was used at 5 mg/kg with probenecid and hydration, weekly for a maximum of 4 weeks, followed by fortnightly maintenance treatment. Four patients were treated with CDV and two of them responded. Both the non-responders developed CMV disease. There was no renal toxicity noted in any of the patients, but three patients had severe vomiting and one developed uveitis, which precluded maintenance treatment in the two responders. Following failure of CDV, foscarnet was effective in controlling the CMV infection in both patients, although the infection recurred in both. Thus, larger randomised studies are required before CDV can be recommended as a primary pre-emptive therapy for post-transplant CMV infections. PMID- 11781650 TI - Infectious complications in breast cancer patients undergoing peripheral blood stem cell transplantation: a single center retrospective analysis towards outpatient strategy. AB - Infectious complications were retrospectively analyzed in 129 transplants, performed in 90 patients, to identify characteristics that qualify breast cancer patients for outpatient-based PBSCT. Thirty-one cases (24%) did not develop fever. Of the remaining 98 cases, 84.7% developed fever during severe neutropenia. On univariate analysis, disease stages II-III, first PBSCT, mucositis grades II-IV and the use of two alkylators were associated with a higher risk of fever development. The latter two factors also affected fever occurrence on multivariate analysis. A longer median time to fever onset was observed in patients conditioned with single as compared to double alkylating agent-containing regimens (respectively 8th vs 6th day, P < 0.00001). As compared with metastatic breast cancer (MBC), high risk breast cancer showed a 2.3-fold increased risk of developing early fever during neutropenia (CI 2.3-3.8), remaining the only variable still significant on multivariate analysis (P = 0.0039). Combination antibiotic therapy was equivalent to single agent therapy. Patients suffering from microbiologically documented fever were at higher risk of undergoing second-line antibiotic therapy. In conclusion, MBC patients treated with a conditioning regimen containing only one alkylating agent and adequate prophylaxis for mucositis may qualify for outpatient-based PBSCT on the basis of a lower risk of infection. PMID- 11781651 TI - Organ dysfunction following stem cell transplantation: relationship to plasma cytokine concentrations. AB - Patients receiving high-dose preparation for stem cell transplantation are at risk for organ dysfunction (OD). Signs of early OD include hypoxia, mental status changes, and liver dysfunction. These early signs have not been correlated with potential cytokine mediators. We compared plasma concentrations of IL-6, TNF alpha, and IL-10 in OD patients and controls. Cytokines were measured before preparation, 5 days before OD, day of OD, and 5 days after OD. TNF-alpha and IL 10 were not measurable prior to preparation. IL-10 was more likely to be measurable in OD patients than in controls 5 days prior to onset of OD (P = 0.039), on the day of OD (P = 0.023), and 5 days later (P < 0.0001). TNF-alpha was more likely to be measurable only on the day of OD (P = 0.0035). IL-6 was significantly elevated in OD patients at all time points. Patients who had measurable IL-6 on admission were 5.1 times more likely to develop OD (95% CI = 1.4-17.9; P = 0.011). Five days prior to OD for each 100 pg/ml increase in IL-6, patients were 2.75 times more likely to develop OD (95% CI = 1.3-5.8; P = 0.0087). The early elevation of IL-6 in patients who develop OD may help identify a high risk group where preventive therapies can be evaluated. PMID- 11781652 TI - Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia. AB - Mylotarg (gemtuzumab zogamicin) is a conjugated monoclonal antibody that has recently become available for use in patients with relapsing or refractory acute myeloid leukemia. Reversible hepatotoxicity is common after administration. We describe the first report of hepatic veno-occlusive disease (HVOD) developing after Mylotarg infusion in a patient who underwent hematopoietic stem cell transplantation 8 months earlier. Certain antineoplastic agents have been implicated as a cause of HVOD, but the disease is most commonly seen within 30 days after hematopoietic stem cell transplantation. The possible association between Mylotarg infusion and HVOD is discussed. PMID- 11781653 TI - A novel type of metastatically spreading subcutaneous aspergillosis without epidermal lesions following allogeneic stem cell transplantation. AB - Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients. PMID- 11781654 TI - Allogeneic stem cell transplantation for Evans syndrome. AB - Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities. PMID- 11781655 TI - A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters. AB - Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of an attenuated mutant of diphtheria toxin A (tox176). Low expression levels of the DT-tox176 result in significant protein synthesis inhibition reflected by a decreased expression of the luciferase activity of a simultaneously transfected CMV luciferase construct. ID50 (dose of plasmid with 50% luciferase inhibition) was calculated for each promoter construct in different cell lines. Highest transactivational activity (ID50 <75 ng) was found for the CMV promoter in all cell lines, which is in agreement with the dual luciferase assay findings. Unlike the dual luciferase findings, however, the DT-tox176 assay showed protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells indicating "leakiness" of these promoter constructs. Low basal promoter activity in nonprostate cell lines was found for the minimal PSA promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better predict basal promoter activity compared to less sensitive dual luciferase assay. PMID- 11781656 TI - Ex vivo purging by adenoviral p53 gene therapy does not affect NOD-SCID repopulating activity of human CD34+ cells. AB - Co-incubation of a replication-deficient, recombinant adenovirus carrying the wild-type p53 gene (rAd-p53) and hematopoietic stem cell (HSC) products from patients with breast cancer can significantly reduce tumor cell contamination. Whereas this approach provides a powerful tumor cell purging strategy, potential detrimental effects on the HSC population have not been investigated. The ability of human HSC to reconstitute hematopoiesis in severe combined immunodeficient (SCID) mice and to undergo secondary transplantation provides the only nonclinical measure of self-renewing, stem cell function. The objective of this study was to investigate whether co-incubation with rAd-p53 compromised the SCID repopulating activity (SRA) of HSC. Granulocyte colony-stimulating factor mobilized human CD34+ cells were co-cultured with rAd-p53 at our targeted clinical dose, and the ability of these cells to establish multilineage hematopoiesis in sublethally irradiated, nonobese diabetic (NOD)-SCID mice was investigated. The persistence of human cells in the mice was investigated by flow cytometry, granulocyte-macrophage colony-forming unit assay, and polymerase chain reaction of human Alu sequences. Further, limiting dilution analysis provided a quantitative comparison between the SRA of CD34+ cells co-incubated with rAd-p53 and control CD34+ cells (no rAd-p53 co-incubation). We conclude that co incubation with rAd-p53 has little effect on the SRA of HSC. PMID- 11781657 TI - Rapid induction of cytotoxic T-cell response against cervical cancer cells by human papillomavirus type 16 E6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector. AB - We have shown that the pulsing of dendritic cells (DCs) with human papillomavirus type 16 (HPV-16) antigen proteins by lipofection stimulates class I-restricted cytotoxic T lymphocyte (CTL) response against primary cervical cancer cells. Also, we have shown that adeno-associated virus (AAV) was able to effectively deliver a cytokine gene into DCs. It has been our hypothesis that the delivery of antigen genes into DCs, resulting in endogenous and continuous antigen protein expression, may result in an improvement in T-cell priming by DCs. Here, DCs are pulsed (infected) with an AAV vector containing the HPV-16 E6 gene. After infection, transduced E6 gene mRNA expression and vector chromosomal integration could be identified in infected DCs. Furthermore, priming rosettes formed at early times when the AAV/E6 vector was used. Most importantly, AAV/E6 vector pulsing of DCs induced, after only 7 days of priming, a strong CTL response against primary cervical cancer cell lines, compared to bacterial E6 protein lipofection. Killing was significantly blocked by the addition of anti-MHC class I antibodies. Fluorescence-activated cell sorter (FACS) analysis of resulting primed cell populations revealed higher levels of CD8+ T cells by AAV-based pulsing, with little evidence of CD56 (NK). FACS analysis of the DC populations revealed that AAV/E6 vector-pulsed DCs had higher levels of CD80 and lower levels of CD86 than protein-pulsed DCs. These data suggest that rAAV may be appropriate for antigen pulsing of DCs for immunotherapy protocols. Finally, our protocol represents an advance in regards to the time needed for generating a CTL response compared to other techniques. PMID- 11781658 TI - Potentiation of a recombinant oncolytic parvovirus by expression of Apoptin. AB - The oncotropic and oncolytic behaviors of certain autonomous rodent parvoviruses make them promising vectors for anticancer gene therapies. However, these parvoviruses are often not potent enough to kill all tumor cells equally well. With the aim of enhancing the intrinsic antitumor effect and the range of natural parvoviruses, a recombinant H1 parvovirus vector was constructed that produces the Apoptin protein, a tumor cell-specific, p53-independent, Bcl-2-insensitive apoptotic effector. We compared the apoptotic activity exerted by a recombinant hH1/Apoptin virus with that of a Green Fluorescent Protein (GFP)-transducing recombinant virus, hH1/GFP, in three human tumor cell lines differing in their susceptibility to wild-type parvovirus H1-induced killing. We found that in cells that were rather resistant to the basal cytotoxic effect of wild-type H1 or the GFP recombinant virus, a parvovirus that expressed Apoptin caused a pronounced, additional cytotoxic effect. In contrast to its enhanced cytotoxicity toward tumor cells, hH1/Apoptin virus was not more toxic to normal human fibroblasts than was the wild-type H1 virus. Taken together, these data indicate that enhancing the oncotropic behavior of wild-type H1 parvoviruses with the tumor specific apoptotic potency of Apoptin should lead to an effective replicative parvoviral vector. PMID- 11781659 TI - Retroviral transduction of human dihydropyrimidine dehydrogenase cDNA confers resistance to 5-fluorouracil in murine hematopoietic progenitor cells and human CD34+-enriched peripheral blood progenitor cells. AB - Severe 5-fluorouracil (5-FU) toxicity has been reported among patients lacking dihydropyrimidine dehydrogenase (DPD) enzymatic activity. DPD is the principal enzyme involved in the degradation of 5-FU to 5'-6'-dihydrofluorouracil, which is further metabolized to fluoro-beta-alanine. We demonstrate here that overexpression of human DPD confers resistance to 5-FU in NIH3T3 cells, mouse bone marrow cells, and in human CD34+-enriched hematopoietic progenitor cells. An SFG-based dicistronic retroviral vector containing human DPD cDNA, an internal ribosomal entry site (IRES), and the neomycin phosphotransferase (Neo) gene was constructed (SFG-DPD-IRES-Neo). Transduced NIH3T3 cells demonstrated a 2-fold (ED50) increase in resistance to a 4-hour exposure of 5-FU in comparison to nontransduced cells. Expression of DPD was confirmed by Northern and Western blot analyses, and DPD enzyme activity was detectable only in transduced cells. Infection of mouse bone marrow cells with this retroviral construct resulted in an increased number of 5-FU-resistant CFU-GM colonies, compared to mock transduced bone marrow in both 4-hour and 12- to 14-day exposures. Infection of human CD34+-enriched cells with this construct and incubation with 5-FU (10(-6) M) for 14 days also resulted in an increased number of 5-FU-resistant colonies. Retroviral transduction of human hematopoietic progenitor cells with a cDNA expressing human DPD conferred resistance to 5-FU in NIH3T3 cells, mouse bone marrow cells, and human CD34+-enriched cells. These results encourage the use of this gene as a method to protect patients from 5-FU myelotoxicity. PMID- 11781660 TI - Induction of systemic antitumor immunity by gene transfer of mammalian heat shock protein 70.1 into tumors in situ. AB - Heat shock proteins (hsps) chaperone cytosolic peptides, forming complexes that stimulate antitumor immunity. Hsps facilitate signal 1 in the two-signal model of T-cell costimulation, whereas cell adhesion molecules such as B7.1 provide secondary (signal 2) costimulatory signals. B7.1 gene transfer into tumors in situ has been shown to eradicate small (<0.3 cm in diameter) tumors in mice, and induce systemic antitumor immunity, but is ineffective against larger tumors. We examine whether mammalian hsps, as facilitators of T-cell costimulation, also exhibit this ability, and whether simultaneously stimulating both signal 1 (hsp facilitated antigen presentation) and signal 2 (B7.1-mediated costimulation) enhances antitumor immunity compared to that achieved with either monotherapy. Prophylactic vaccination of mice with an hsp preparation from an EL-4 lymphoma weakly retarded tumor growth, to the same extent as that achieved with a single EL-4-derived peptide (AQHPNAELL), previously shown to induce antitumor immunity establishing that a preparation of EL-4 hsp-peptide complexes has antitumor activity. Here we show that injection of rat hsp70.1 into mouse tumors in situ causes the complete eradication of tumors, and generates potent systemic antitumor immunity mediated by CD4+ and CD8+ T cells. Unexpectedly, simultaneous gene transfer of hsp70.1 and B7.1 compromised the efficacy of hsp-mediated tumor rejection--a problem which could be partially overcome by the timed delivery of hsp70.1 and B7.1. Thus, gene transfer of hsp70 into tumors can be employed to generate potent systemic antitumor immunity, but further consideration is required if this approach is to be successfully combined with immunotherapies employing other T-cell costimulators. PMID- 11781661 TI - Evaluation of endostatin antiangiogenesis gene therapy in vitro and in vivo. AB - Progressive growth and metastasis of solid tumors require angiogenesis, or the formation of new blood vessels. Endostatin is a 20-kDa carboxy-terminal fragment of collagen XVIII that has been shown to inhibit endothelial cell proliferation and tumor angiogenesis. Replication-deficient recombinant adenovirus (rAd) vectors were constructed, which encoded secreted forms of human and mouse endostatin (HECB and MECB, respectively), and, as a control, human alkaline phosphatase (APCB). Accumulation of endostatin was demonstrated in supernatants of cultured cells infected with the endostatin rAds. These supernatants disrupted tubule formation, inhibited migration and proliferation, and induced apoptosis in human dermal vascular endothelial cells or human vascular endothelial cells. Endostatin-containing supernatants had no effect on the proliferation of MidT2-1 mouse mammary tumor cells in vitro. A pharmacokinetic study of MECB in immunocompetent FVB mice demonstrated a 10-fold increase of serum endostatin concentrations 3 days after intravenous administration of 1x10(10) particles of this rAd (215-257 ng/mL compared to 12-38 ng/mL in control rAd-treated mice). Intravenous administration of MECB reduced b-FGF stimulated angiogenesis into Matrigel plugs by 38%. Intratumoral MECB inhibited growth of MidT2-1 syngeneic mammary tumors in FVB mice, but had minimal impact on the growth of MDA-MB-231 human breast tumors in SCID mice. Intravenous therapy with MECB also initially inhibited growth of MidT2-1 tumors, but this activity was subsequently blocked by induced anti-rAd antibodies. In summary, endostatin gene therapy effectively suppressed angiogenic processes in vitro and in vivo in several model systems. PMID- 11781662 TI - Midkine and cyclooxygenase-2 promoters are promising for adenoviral vector gene delivery of pancreatic carcinoma. AB - Midkine (MK), a heparin binding growth factor, and cyclooxygenase-2 (COX-2), a key enzyme in the conversion of arachidonic acid to prostaglandin, are both up regulated at the mRNA or protein level in many human malignant tumors. Here, we investigated the tumor specificity of both MK and COX-2 promoters in human pancreatic cancer, with the aim to improve the selectivity of therapeutic gene expression. We constructed recombinant adenoviral (Ad) vectors containing either the luciferase (Luc) reporter gene under the control of the COX-2 or MK promoter or the herpes simplex virus thymidine kinase (HSV Tk) gene under the control of the COX-2 promoter and compared the expression with the cytomegalovirus (CMV) promoter. AdMKLuc achieved moderate to relatively high activity upon infection to both primary and established pancreatic carcinoma cells. Of the two COX-2 promoter regions (COX-2M and COX-2L), both revealed a high activity in primary pancreatic carcinoma cells, whereas in the established pancreatic carcinoma cell lines, COX-2L has an approximately equal high activity compared to CMV. In addition, both AdCOX-2M Tk and AdCOX-2L Tk induced marked cell death in response to ganciclovir (GCV) in three of four established pancreatic carcinoma cell lines. From these results, and because it has been reported that AdMKTk and AdCOX 2L Tk in combination with GCV did not reveal significant liver toxicity, we conclude that the MK as well as the COX-2 promoters are promising tumor-specific promoters for Ad vector-based gene therapy of pancreatic cancer. PMID- 11781666 TI - Head and Neck Imaging. PMID- 11781663 TI - Tissue-specific expression of a suicide gene for selective killing of neuroblastoma cells using a promoter region of the NCX gene. AB - The human NCX gene, a homologue of the murine neural crest homeobox (Ncx/Hox11L.1) gene whose expression is restricted to a subset of neural crest derived tissues, was expressed in human neuroblastoma cells but not in other tumors or fibroblasts. A 4.5-kb genomic fragment in the 5'-flanking region of the NCX gene efficiently transcribed the fused luciferase reporter gene in human neuroblastoma cells but not in non-neuroblastoma cells. Sequential deletion of this regulatory region from the 5' side demonstrated that a 1.7-kb fragment upstream from the start codon retained the preferential promoter activity in neuroblastoma cells. The transcriptional activation by the NCX promoter was stronger than that by the SV40 T antigen promoter in human neuroblastoma cells. Transfection of neuroblastoma cells with the NCX promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene increased their sensitivity to ganciclovir. The regulatory region of the NCX gene is thus useful for neuroblastoma-specific suicide gene therapy. PMID- 11781668 TI - The influence of fish, meat and polyunsaturated fat intakes on platelet phospholipid polyunsaturated fatty acids in male Melbourne Chinese and Caucasian. AB - OBJECTIVE: The aims of this study were to investigate (1) platelet phospholipid (PL) polyunsaturated fatty acid (PUFA) composition in subjects who were the Melbourne Chinese migrants, compared with those who were the Melbourne Caucasians and (2) the relationship between platelet PL PUFA and intake of fish, meat and PUFA. DESIGN: Cross-sectional comparison of the Melbourne Chinese and Caucasians. SETTING: Free-living male subjects. SUBJECTS: Ninety-seven Melbourne Chinese migrants and 78 Melbourne Caucasians who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The platelet PUFA was measured by gas-liquid chromatography. RESULTS: The Melbourne Chinese had significantly higher proportions of platelet PL 20:5n-3 (P=0.006), 22:6n-3 (P<0.0001), total n-3 (P=0.027) and 22:5n-6 (P=0.0002), and a significantly higher intake of fish (P=0.012) and white meat (P=0.0045) compared with the Melbourne Caucasians. In addition, the Melbourne Chinese had significantly lower proportions of 20:3n-6 (P=0.023), 20:4n-6 (P<0.002), 22:4n-6 (P<0.0001), total n-6 (P=0.037), 22:5n-3 (P<0.0001) and ratio of n-6/n-3 (P=0.011), and a significantly lower intake of red and total meat (P<0.0001) than the Melbourne Caucasians. Fish consumption was significantly positively correlated with platelet PL 20:5n-3 and 22:6n-3, and significantly negatively correlated with 22:5n-3 (P<0.05). Meat consumption was significantly positively correlated with 22:5n-3 and significantly negatively correlated with 22:5n-6, 20:5n-3 and 22:6n-3 (P<0.05). Dietary PUFA intake was significantly positively correlated with 20:3n-6, 22:4n-6 and 22:5n-3, and significantly negatively correlated with 22:5n-6, 20:5n-3 and 22:6n-3 (P<0.05). CONCLUSIONS: Compared with Caucasians, the Melbourne Chinese had a significantly higher level of platelet PL n-3 PUFA, which might contribute to the low CVD mortality in this population. Platelet PL 20:5n-3 and 22:6n-3 were significantly positively correlated with fish intake, and negatively significantly correlated with dietary intake of meat and PUFA, while 22:5n-3 was significantly positively correlated with dietary meat and PUFA intake, and significantly negatively correlated with fish intake. Dietary intake of PUFA and fish are potential confounding factors for assessing the effects of meat consumption on platelet PL individual PUFA. Dietary intake of PUFA and meat did not influence the incorporation of fish long chain n-3 PUFA to platelet PL in this study population. SPONSORSHIP: Palm Oil Research Institute of Malaysia, Meat Research Corporation Australia. PMID- 11781669 TI - The molar ratio of serum retinol-binding protein (RBP) to transthyretin (TTR) is not useful to assess vitamin A status during infection in hospitalised children. AB - OBJECTIVE: To assess the usefulness of the molar ratio of serum retinol-binding protein (RBP) to transthyretin (TTR) to determine vitamin A (VA) status during infection. DESIGN: We took advantage of previously collected data during a randomised double-blind, placebo-controlled clinical trial to conduct a secondary analysis of the RBP/TTR ratio and its relationship to infection and VA status. In this clinical trial, children were randomly assigned to one of three groups and received either one single oral high dose of VA (200 000 IU) on the day of admission and subsequently a placebo daily until discharge or daily oral low doses of VA (5000 IU) from admission until discharge or a placebo daily from admission until discharge. SETTING: Lwiro pediatric hospital, Province of South Kivu, Democratic Republic of Congo. SUBJECTS: A total of 900 children aged 0-72 months hospitalised consecutively between March 1994 and March 1996. MAIN OUTCOME MEASURES: RBP/TTR molar ratio after 7 days hospitalisation. RESULTS: After 7 days hospitalisation, molar RBP:TTR ratio (mean+/-s.d.) of infected children (C reactive proteins>10 mg/l) was 0.67+/-0.31 in the high-dose group (n=81), 0.74+/ 0.44 in the low dose group (n=71) and 0.73+/-0.39 in the placebo group (n=81). These values did not differ significantly (one-way ANOVA P=0.472). In patients with baseline serum retinol concentrations<0.70 micromol/l, changes in RBP:TTR ratio between admission and day 7 were not statistically different in the three groups (one-way ANOVA P=0.548). CONCLUSIONS: In this population of malnourished hospitalised children, molar RBP:TTR ratio does not appear to be useful to assess VA status during infection. SPONSORSHIP: Our research was partially supported by a grant from the Fonds de la Recherche Scientifique et Medicale (contract 3.4505.94) and the David and Alice Van Buuren Foundation. PMID- 11781670 TI - Nutritional treatment for acquired immunodeficiency virus infection using an enterotropic peptide-based formula enriched with n-3 fatty acids: a randomized prospective trial. AB - OBJECTIVE: Dietary counseling and intervention based on application of conventional criteria have been ineffective in preventing the progressive weight loss associated with HIV infection. The aim of the study was to compare the progression of clinical and nutritional indicators during nutritional supplementation with or without an enterotropic peptide-based formula enriched with n-3 fatty acids. DESIGN: Randomized trial. SETTING: Tertiary care. SUBJECTS: Ninety-one patients were screened for the study. Twenty-three did not meet the inclusion criteria, therefore 74 patients were randomized. Of these, 38 were randomized to group I (standard formula) and 36 were randomized to group II supplementation (enterotropic peptide-based formula enriched with n-3 fatty acids). INTERVENTIONS: Group I received standard enteral formula and group II received a enterotropic peptide-based enteral formula. The volume was the same (3 cans/day, 236 ml per can). In both groups enteral supplementation were recommended in conjunction with a registered dietitian under a dietary counseling program based on standard nutrition principles. Patients received a prospective serial assessment of nutrition status, nutritional intake with 24 h written food records, GI symptoms, immune function, anthropometric status and intercurrent health events including infections and hospitalization. These determinations were performed at baseline and at 3 months. RESULTS: Treatment with both supplements resulted in a significant and sustained increase in weight (3.2% in group I and 3.1% in group II); this increase was mostly due to fat mass (12.8% in group I) and (7.5% in group II). Total body water and fat free-mass remained unchanged. CD4 counts remained stable in group I, while a significant increase was detected in group II (576+/-403 vs 642+/-394 cells/mm(3); P<0.05). After the 3 month period CD4 counts remained higher in group II. Hospitalization events (infections) were also followed during the 3 month period. Group II had fewer hospitalizations than group I, but no statistical differences were found. CONCLUSIONS: Oral nutritional supplements for a 3 month period were well tolerated and resulted in body weight gain in HIV-infected patients. Supplement enriched formula, with peptides and n-3 fatty acids, increased CD4 count. PMID- 11781671 TI - Nutrition and cognitive deficit in the elderly: a population study. AB - OBJECTIVE: To investigate the association between a healthy diet indicator and the prevalence of cognitive impairment in the elderly. DESIGN: Cross-sectional study. SETTING: Population based. SUBJECTS: A total of 1651 subjects (560 men and 1091 women) including everybody aged 70 y or more, and a random sample of people (about 40%) aged 65-69 y resident in four rural towns in the province of Pavia, Italy in 1992-1993. INTERVENTIONS: The healthy diet indicator based on the WHO guidelines for the prevention of chronic diseases was calculated as reported by Huijbregts et al (1998; Eur. J. Clin. Nutr. 52, 826-831). Food intake was estimated by means of a 180-item food-frequency questionnaire and nutrient intake was calculated using the food composition database compiled for epidemiologic studies in Italy. The cognitive function was categorized into four levels-normal cognition, mild, moderate and severe cognitive deficit-according to the neuropsychological test score. The relationship between the dietary and the ordinal cognitive function variables was studied using the proportional-odds model. RESULTS: After adjustment for age, sex, education, total energy intake, cigarette smoking, alcohol consumption and physical activity, a better healthy diet score was associated with a lower prevalence of cognitive deficit. The cumulative odds ratio was 0.85 (95% CI 0.77-0.93). CONCLUSIONS: Our results suggest an association between a globally satisfactory diet and better cognitive performance in the elderly. However, the specific aspects of a 'healthy diet' for the elderly should be clarified. SPONSORSHIP: National Research Council (Italy), 'Invecchiamento' Project no. 95.01048.PF40. PMID- 11781672 TI - The energy expenditure of postmenopausal women classified as restrained or unrestrained eaters. AB - OBJECTIVE: Restrained eating is a common dietary practice among individuals who are attempting to prevent weight gain, but little is known about differences in energy physiology and regulation between restrained and unrestrained eaters. We investigated this issue in non-obese free-living postmenopausal women classified as long-term restrained (n=26) or unrestrained (n=34) eaters group matched for body mass index (BMI). MEASUREMENTS: Measurements were made of total energy expenditure (TEE), resting energy expenditure (REE), body composition, reported leisure time activity, maximal aerobic capacity (VO2max) and weight change during the study period. In addition, physical activity level (PAL) and nonexercise activity thermogenesis (NEAT) were calculated from measured variables. RESULTS: There were no significant differences between the groups in body composition, weight change, aerobic capacity or total leisure time activity. Relationships between fat-free mass (FFM) and both REE and TEE, and the relationship between work load and energy expenditure in the test of maximal oxygen consumption, were also not different between groups. However, restrained eaters had a significantly lower PAL (equal to TEE/REE, 1.72+/-0.04 vs 1.84+/-0.04, P<0.05). In addition, in multiple regression models predicting NEAT, NEAT was significantly lower in restrained eaters than unrestrained eaters and there was a positive relationship between NEAT and weight change in unrestrained eaters but no relationship in restrained eaters (P<0.05). CONCLUSIONS: In contrast to a previous report, we found no significant difference in TEE between restrained and unrestrained eaters. PAL was slightly lower in restrained eaters, apparently due to reduced NEAT, and restrained eaters also lacked the positive association between NEAT and body weight change seen in unrestrained eaters. This latter finding, if confirmed in future studies, could help explain an increased susceptibility of restrained eaters to weight gain. SPONSORSHIP: NIH grants AG12829, DK46124 and T32AG00209, and US Cooperative Agreement number 58-1950-9-001. PMID- 11781673 TI - Haemoglobin status of adult non-pregnant Kazakh women living in Kzyl-Orda region, Kazakhstan. AB - OBJECTIVE: To estimate the prevalence of anaemia among adult non-pregnant women in the Kzyl-Orda region of Kazakhstan, and to determine the association between haemoglobin concentration and anthropometric, socioeconomic, reproductive and dietary factors. DESIGN: A cross-sectional study using a randomly selected sample. Subjects were interviewed, and finger-prick blood samples and anthropometric measurements were collected. Associations between haemoglobin concentration and anthropometric and questionnaire data were evaluated by sequential linear regression analysis. SETTING: Health centres in Kazalinsk, Djalagash and Zhanakorgan districts of Kzyl-Orda region, Kazakhstan. SUBJECTS: Three-thousand six-hundred and twenty-five non-pregnant women aged 18-45 y randomly selected from health centre records. RESULTS: Iron deficiency anaemia, as reflected by low haemoglobin levels (Hb<12 g/dl), was detected in 40.2% of the total sample. There was a significant curvilinear relationship between haemoglobin concentration and age, with the nadir of the curve in the 30-40 y age group. Haemoglobin concentration was found to be positively associated with body mass index (BMI) and socioeconomic factors. Significant negative associations were found between haemoglobin concentration and duration of menses, use of the intra-uterine contraceptive device and the consumption of tea. CONCLUSIONS: This study demonstrates that iron deficiency anaemia is present at considerable levels among adult women living in Kzyl-Orda region, Kazakhstan, and provides important baseline information for future research and public health interventions. SPONSORSHIP: Funding was provided by the United States Agency for International Development, Office of Nutrition, the United Kingdom Department for International Development, and the Polden-Puckham Trust. PMID- 11781674 TI - The glycaemic index values of Vietnamese foods. AB - OBJECTIVE: To determine and compare the glycaemic index (GI) values of a range of Vietnamese foods in two racial groups. DESIGN AND SUBJECTS: Twelve healthy subjects (six Asian and six Caucasian) consumed 50 g carbohydrate portions of a reference food (glucose sugar) and nine Vietnamese foods (three rices, three noodle products and three sweet foods) in random order after an overnight fast. The reference food was tested on two separate occasions, and the Vietnamese foods were each tested once. Capillary blood samples were taken at time 0 (fasting), 15, 30, 45, 60, 90 and 120 min from the start of each meal. Samples were analysed for plasma glucose and the incremental areas under the plasma glucose curves (AUC) were used to calculate the GI values of the test foods, using glucose as the reference food (ie GI value of glucose=100). The mean GI value of each food was calculated for the entire group of subjects (n=12) and for both racial groups (n=6). RESULTS: The three rices had surprisingly high GI values (86-109), whereas the noodle products had relatively low GI values (39-61). The sugar-rich foods produced intermediate GI values (54-79). The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other (P=0.26). CONCLUSIONS: The GI values derived from Caucasian subjects are likely to be applicable to Asian populations. Varieties of imported rice from Thailand were found to have high GI values. Alternative low-GI staples, such as rice noodles, may be preferable for Asian/Vietnamese people with diabetes. SPONSORSHIP: This study was funded by the University of Sydney. PMID- 11781675 TI - Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. AB - OBJECTIVES: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine. DESIGN: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g) containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested. SUBJECTS: Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2. MAIN OUTCOME MEASURES: Plasma lipids, plasma sterols, plasma carotenoids and tocopherols. RESULTS: Study 1-median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison). CONCLUSION: 1. Plant sterol esters and non esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study. SPONSORSHIP: Meadow Lea Foods, Australia. PMID- 11781676 TI - Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. AB - OBJECTIVE: We asked whether women self-reporting the recommended consumption of vitamin D from milk and multivitamins would be less likely to have low wintertime 25-hydroxyvitamin D (25(OH)D) levels. METHODS: This cross-sectional study enlisted at least 42 young women each month (age 18-35 y, 796 women total) through one year. We measured serum 25(OH)D and administered a lifestyle and diet questionnaire. RESULTS: Over the whole year, prevalence of low 25(OH)D (<40 nmol/l) was higher in non-white, non-black subjects (25.6% of 82 women) than in the white women (14.8% of 702 white women, P<0.05). Of the 435 women tested during the winter half of the year (November-April), prevalence of low 25(OH)D was not affected by vitamin D intake: low 25(OH)D occurred in 21% of the 146 consuming no vitamin D, in 26% of the 140 reporting some vitamin D intake, up to 5 microg/day (median, 2.5 microg/day), and in 20% of the 149 women reporting vitamin D consumption over 5 microg/day (median, 10 microg/day). INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. Vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration. PMID- 11781677 TI - Fractional zinc absorption using a single isotope tracer. AB - BACKGROUND: Fractional absorption of zinc (Zn) has been measured using dual isotopes of Zn given simultaneously. An oral test dose and an intravenous (i.v.) reference dose are administered, followed by the measurement of the double isotopic enrichment (E) in urine 48 h after administration. We postulated that an estimate of the %E in urine for a given i.v. dose of Zn may be used to eliminate the need for venipuncture and the second Zn isotope. OBJECTIVES: To determine a constant (k) for the Zn enrichment of urine after i.v. administration of a dose of labeled Zn in Zn-replete subjects. To use 'k' to calculate fractional absorption of Zn, and to compare these values to values obtained using the standard dual isotope method. DESIGN: Single-arm cohort. SETTING: The Hospital for Sick Children, Toronto, Canada. SUBJECTS: Twenty-three healthy adults were recruited from the Metropolitan Toronto area. Seventeen subjects completed the study. INTERVENTIONS: A 2.29 mg i.v. dose of (67)Zn followed immediately by a 2.50 mg oral dose of (70)Zn. RESULTS: Population mean percentage enrichment (%E) of (67)Zn in urine was 1.43 (95% CI 1.26, 1.60). The ratio of the i.v. dose to mean %E in urine (k) was estimated to be 1.60 mg (95% CI 1.43, 1.82). There was no difference in the mean fractional absorption of Zn calculated using the single compared to the dual isotope method: 12.58% (95% CI 2.22, 22.94) vs 12.68% (95% CI 4.52, 20.85), respectively (P=0.89). The correlation coefficient between the two methods was 0.81 (P<0.0001). CONCLUSIONS: The dual isotope method may be replaced by using a constant (k) and a single oral dose of isotopic-enriched Zn to estimate fractional absorption of Zn within a population. SPONSORSHIP: Gerber Products Company, Fremont, MI. PMID- 11781678 TI - Sociodemographic and health behaviour factors among dietary supplement and natural remedy users. AB - OBJECTIVE: To investigate which subgroups of the Swedish adult population use dietary supplements and natural remedies, taking into account sociodemographic and health behaviour factors. DESIGN: A cross-sectional survey conducted in 1996/1997 by Statistics Sweden was used for the analyses. In face-to-face interviews participants reported consumption of dietary supplements and natural remedies during the previous 2 weeks. SETTING: Sweden SUBJECTS: A nationally representative sample of 11 422 adults (5596 men, 5826 women) aged 16-84 y. The response rate was 78%. RESULTS: Overall, 33% of Swedish women and 22% of Swedish men reported use of dietary supplements; prevalence of natural remedy users was 14 and 7%, respectively. The best predictors for use of dietary supplements and natural remedies were age, sex and subjective health. Women and older individuals were more likely to be dietary supplement and/or natural remedy users. Obese men and women were less likely to use dietary supplements than underweight ones. Among men subjective health was significantly related to use of these preparations. Men who reported excellent health ate less than men reporting poor health. This association was weaker among women. Exercise was another important factor. Both men and women (except female dietary supplement users) who reported moderate or heavy exercise were significantly more frequent users of these preparations than those who reported practically no exercise. CONCLUSION: Use of dietary supplements and natural remedies is associated with several sociodemographic and health behaviour factors. SPONSORSHIP: Karolinska Institutet Research Fund. PMID- 11781679 TI - Evaluation of nonglucose carbohydrates in parenteral nutrition for diabetic patients. AB - OBJECTIVE: There is little information on the advantages of nonglucose carbohydrates in total parenteral nutrition (TPN) for diabetic patients. The aim of this study is to evaluate glycemic control and insulin requirements in diabetic patients who received TPN with different sources of carbohydrates, and to determine whether insulin requirements are different when septic and non septic diabetic patients are studied. MATERIALS AND METHODS: One-hundred and thirty-eight patients were randomly divided into two groups receiving either glucose (G), n=71, or glucose-fructose-xylitol 2:1:1 (GFX), n=67. There were no differences between the demographic or anthropometric characteristics of the groups, nor between the patients with diabetes mellitus type 1 and type 2, nor the initial TPN composition. Acceptable glycemic control was considered when glycemia reached <200 mg/dl. RESULTS: Glycemic control was attained in 79.7% of patients (74.6 vs 85.1%), in the same period of treatment. At the end of treatment, insulin requirements were not different (45+/-19 vs 45+/-26 UI/day) in both groups, while similar amounts of carbohydrates (191+/-36 vs 187+/-45 g/day) were infused. The ratio insulin/body weight and insulin/carbohydrates were equal in both groups. In the GFX group nonseptic and septic patients needed less and more insulin, respectively, than their counterparts in the G group. No major adverse events related to carbohydrate infusions were observed. CONCLUSIONS: Either G or GFX could be used in TPN for diabetic patients, providing glycemic control in most cases with similar insulin requirements. GFX mixtures were slightly more beneficial to attain glycemic control in nonseptic patients, but septic diabetic patients had higher insulin needs in this group. PMID- 11781682 TI - Medical genomics. PMID- 11781683 TI - Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease. AB - Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37x10(-4)) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1. PMID- 11781684 TI - Identification of a nonsense mutation in the PAX9 gene in molar oligodontia. AB - Development of dentition is controlled by numerous genes, as has been shown by experimental animal studies and mutations that have been identified by genetic studies in man. Here we report a nonsense mutation in the PAX9 gene that is associated with molar tooth agenesis in a Finnish family. The A340T transversion creates a stop codon at lysine 114, and truncates the coded PAX9 protein at the end of the DNA-binding paired-box. All the affected members of the family were heterozygous for the mutation. The tooth agenesis phenotype involves all permanent second and third molars and most of the first molars and resembles the earlier reported phenotype that was also associated with a PAX9 mutation. The phenotype is presumably a consequence of haploinsufficiency of PAX9. In another Finnish family with molar tooth agenesis, we could not find similar sequence changes in PAX9. PMID- 11781685 TI - Mapping of the second locus for the Van der Woude syndrome to chromosome 1p34. AB - The Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, cleft lip and/or cleft palate. It is the most common cleft syndrome. VWS has shown remarkable genetic homogeneity in all populations, and so far, all families reported have been linked to 1q32-q41. A large Finnish pedigree with VWS was recently found to be unlinked to 1q32-q41. In order to map the disease locus in this family, a genome wide linkage scan was performed. A maximum lod score of 3.18 was obtained with the marker D1S2797, thus assigning the disease locus to chromosomal region 1p34. By analyses of meiotic recombinants an approximately 30 cM region of shared haplotypes was identified. The results confirm the heterogeneity of the VWS syndrome, and they place the second disease locus in 1p34. This finding has a special interest because the phenotype in VWS closely resembles the phenotype in non-syndromic forms of cleft lip and palate. PMID- 11781686 TI - A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. AB - Seckel syndrome (MIM 210600) is a rare autosomal recessive disorder with a heterogeneous appearance. Key features are growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance. We have performed a genome-wide linkage scan in a consanguineous family of Iraqi descent. By homozygosity mapping a new locus for the syndrome was assigned to a approximately 30 cM interval between markers D18S78 and D18S866 with a maximum multipoint lod score of 3.1, corresponding to a trans-centromeric region on chromosome 18p11.31-q11.2. This second locus for Seckel syndrome demonstrates genetic heterogeneity and brings us a step further towards molecular genetic delineation of this heterogeneous condition. PMID- 11781687 TI - A genome-wide scan for preeclampsia in the Netherlands. AB - Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New Zealand (NZ). The current study reports on a genome-wide scan of Dutch affected sib-pair families. In total 67 Dutch affected sib-pair families, comprising at least two siblings with proteinuric preeclampsia, eclampsia or HELLP-syndrome, were typed for 293 polymorphic markers throughout the genome and linkage analysis was performed. The highest allele sharing lod score of 1.99 was seen on chromosome 12q at 109.5 cM. Two peaks overlapped in the same regions between the Dutch and Icelandic genome wide scan at chromosome 3p and chromosome 15q. No overlap was seen on 2p. Re analysis in 38 families without HELLP-syndrome (preeclampsia families) and 34 families with at least one sibling with HELLP syndrome (HELLP families), revealed two peaks with suggestive evidence for linkage in the non-HELLP families on chromosome 10q (lod score 2.38, D10S1432, 93.9 cM) and 22q (lod score 2.41, D22S685, 32.4 cM). The peak on 12q appeared to be associated with HELLP syndrome; it increased to a lod score of 2.1 in the HELLP families and almost disappeared in the preeclampsia families. A nominal peak on chromosome 11 in the preeclampsia families showed overlap with the second highest peak in the Australian/NZ study. Results from our Dutch genome-wide scan indicate that HELLP syndrome might have a different genetic background than preeclampsia. PMID- 11781688 TI - DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations. AB - The present study investigates the molecular basis of the G3m polymorphism expressed by the heavy constant domains of human immunoglobulins gamma 3 chains. By using a new protocol allowing the specific cloning of IGHG3 genes, a total of 51 full-length IGHG3 genomic sequences (about 2 kb) isolated from African, Siberian, West Asian and European population samples were sequenced. IGHG3 sequences were assigned precise G3m haplotypes on the basis of specific associations between G3m allotypes and IGHG3 RFLPs. Specific DNA substitutions involved in the expression of G3m(5), G3m(6), G3m(15), G3m(16), G3m(21), G3m(24) and G3m(28) allotypes were then deduced, elucidating almost completely the determination of the G3m polymorphism at the DNA level. The molecular evolution of G3m haplotypes was investigated by a maximum likelihood phylogeny of IGHG3 sequences. Sequence clusters are shown to be G3m haplotype-specific, corroborating the Gm molecular model deduced from serology, and showing that populations differentiation is much more recent than G3m haplotypes differentiation. The widely distributed G3m(5,10,11,13,14) haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas. PMID- 11781689 TI - Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families. AB - The 999del5 mutation is the single, strong BRCA2 founder mutation in Iceland and the most common BRCA1/2 founder mutation in Finland. To evaluate the origin and time since spreading of the 999del5 mutation in Iceland and in Finland, we constructed haplotypes with polymorphic markers within and flanking the BRCA2 gene in a set of 18 Icelandic and 10 Finnish 999del5 breast cancer families. All Icelandic families analysed shared a common core haplotype of about 1.7 cM. The common ancestors for the Icelandic families studied were estimated to trace back to 340-1000 years, not excluding the possibility that the mutation was brought to Iceland during the settlement of the country. Analysis of the Finnish families revealed two distinct haplotypes. A rare one, found in three families in the old settlement region in southwestern Finland, shared a four-marker (0.5 cM) core haplotype with the Icelandic 999del5 haplotype. A distinct approximately 6 cM haplotype was shared by seven 999del5 Finnish families estimated to have a common ancestry 140-300 years ago. These families cluster in two geographical regions in Finland, in the very same area as those with the rare haplotype and also in the most eastern, late settlement region of Finland. The results may indicate a common ancient origin for the 999del5 mutation in Iceland and in Finland, but distinct mutational events cannot be ruled out. The surprising finding of the same mutation in two completely different haplotypes in a sparsely populated area in Finland may suggest gene conversion. PMID- 11781690 TI - Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms. AB - Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. The aims of this study were to identify the factors affecting MPO serum concentration, to study the familial resemblance of MPO levels and to investigate the association between newly described MPO polymorphisms as well as the G-463A one and MPO levels in a healthy population. MPO serum concentrations were measured by an enzymatic immuno-assay (EIA) in 82 healthy families of the STANISLAS Cohort and MPO genotype, determination was performed using PCR-restriction fragment length polymorphism or allele specific oligonucleotide assay. MPO concentrations were significantly higher in parents than in offspring. The factors affecting MPO levels were age, the number of white cells, smoking in fathers and oral contraceptive intake in mothers. They explain from 12.4% up to 35.9% of MPO variability in men and women, respectively. Family correlations of MPO concentrations were of similar magnitude. The -129A allele of a newly described G-129A substitution was significantly associated with decreased MPO levels, whereas the -463A allele was suggested to be associated with increased levels of lipid variables. In this study, we identified factors affecting MPO serum concentrations and showed that molecular variations of the gene have only a weak influence on MPO variability. In contrast, the association between the G-463A polymorphism and lipid levels would suggest a possible implication of MPO in the risk of cardiovascular diseases. These results have to be confirmed and further investigations will be conducted in that way. PMID- 11781691 TI - The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation. AB - The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cM. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cM was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the P(excess) and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago. PMID- 11781692 TI - Absence of the HIV-1 protective Delta ccr5 allele in most ethnic populations of India. AB - Recent epidemiological data and projections indicate that HIV infection will spread rapidly in India. An allele Delta ccr5 of the beta-chemokine receptor gene CCR5 has been found to confer protection against HIV-1. We find that this protective allele is absent in most ethnic populations of India, except some populations of the northern and western regions where this allele may have been introduced by Caucasian gene flow. The implications of this finding are discussed in the light of increasing HIV prevalence in India. PMID- 11781693 TI - The angiotensin converting enzyme I/D polymorphism in Russian athletes. AB - The deletion (D) allele of the human ACE gene is associated with higher ACE activity than the insertion (I) allele. There is controversy as to whether the ACE genotype may be associated with elite athletic status; recent studies have identified no significant associations amongst those drawn from mixed sporting disciplines. However, such lack of association may reflect the mixed nature of such cohorts, given that an excess frequency of the I allele has been reported amongst elite endurance athletes, and an excess of the D allele amongst those engaged in more power-orientated sports. We examined this hypothesis by determining ACE I/D allele frequency amongst 217 Russian athletes (swimmers, skiers, triathletes and track-and-field participants) prospectively stratified by performance ('outstanding' or 'average'), and the duration of their event (SDA (<1 min), MDA (1 to 20 min), and LDA (>20 min): short, middle and long distance athletes respectively). ACE genotype and allele frequencies were compared to 449 controls. ACE genotype frequency amongst the whole cohort, or the outstanding athletes alone, was no different to that amongst sedentary controls. However, there was an excess of the D allele (frequency 0.72, P=0.001) amongst the outstanding SDA group, and an excess of the I allele (frequency 0.63, P=0.032) amongst the outstanding MDA group. These findings were replicated in the outstanding swimmers, with track and field SDA similarly demonstrating an excess of the D allele (P=0.01). There was no association found between the outstanding LDA and ACE genotype (P=0.27). These data not only confirm an excess of the D allele in elite SDA, and I allele in elite MDA, but also offer an explanation as to why any such association may be hard to detect amongst a heterogeneous cohort of mixed athletic ability and discipline. PMID- 11781694 TI - Investigations of a CA repeat in the oestrogen receptor beta gene in patients with Alzheimer's disease. AB - Several studies have shown that oestrogen treatment after menopause decreases the risk for Alzheimer's disease (AD). It is also known that oestrogen stimulates the outgrowth of nerve cells and that apolipoprotein E (Apo E) synthesis and amyloid precursor protein (APP) metabolism are regulated by oestrogen. Recently a new oestrogen receptor was identified, oestrogen receptor beta (ERbeta), located at chromosome 14q22-24. Several genes close to this chromosomal region have been implicated in AD, but the results are conflicting. Our hypothesis was that variations in the ERbeta gene could be the underlying cause to the positive findings in these genes and we have therefore investigated a CA repeat(1) in intron 5 of the ERbeta gene. Three hundred and thirty-six AD cases and 110 healthy age-matched controls were included in this study. Fourteen different alleles were found with frequencies between 0.1 and 37%. There was no significant difference between AD cases and controls when all alleles were compared. However, allele 5 was seen in 13.6% of the controls but only in 8.0% of AD cases (P=0.014; odds ratio (OR)=0.55). No AD patient homozygous for this allele was seen but three controls were homozygous. In conclusion, our findings suggest the ERbeta allele 5 to be a protective factor. However, this has to be confirmed in a larger population. PMID- 11781695 TI - An mtDNA mutation, 14453G-->A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome. AB - We report a novel point mutation in the gene for the mitochondrially encoded ND6 subunit of the NADH:ubiquinone oxidoreductase (complex I of the respiratory chain) in a patient with MELAS syndrome. The mutation causes a change from alanine to valine in the most conserved region of the ND6 subunit. The patient was heteroplasmic for the mutation in both muscle and blood, but the mutation was not detected in the patient's mother. A marked reduction of complex I activity was found in the patient's muscular tissue. This is the first report of a mutation in the ND6 subunit causing MELAS. Our data confirm the genetic heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes syndrome, and confirms that MELAS can be caused by mutation in polypeptide-coding mtDNA genes. PMID- 11781696 TI - High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. AB - We report here a comparison of serum endostatin levels in Down syndrome patients to normal control subjects. We analysed serum samples from 35 patients with Down syndrome and 54 normal control subjects and found that although serum levels of endostatin vary widely in a normal human population, serum endostatin levels are significantly elevated in patients with Down syndrome. This result may explain the relative decrease in incidence of various solid tissue tumours observed in Down syndrome, given the role of endostatin as a potent inhibitor of tumour induced angiogenesis in both human and animal models. Based upon these data, we propose that an increase of about one-third of normal endostatin serum levels may represent an effective therapeutic dose to significantly inhibit many solid tumours. PMID- 11781697 TI - LDL receptor-GFP fusion proteins: new tools for the characterisation of disease causing mutations in the LDL receptor gene. AB - The function of a series of LDL receptor GFP fusion proteins with different, flexible, unstructured spacer regions was analysed. An optimised version of the fusion protein was used to analyse the effect of an LDL receptor mutation (W556S) found in FH patients and characterised as transport defective. In cultured liver cells this mutation was found to inhibit the transport of LDL receptor GFP fusion protein to the cell surface, thus leading to impaired internalisation of fluorescent labelled LDL. Co-localisation studies confirmed the retention of the mutant protein in the endoplasmic reticulum. Wild type (WT) and W556S LDL receptor GFP fusion proteins were expressed in mouse liver by means of hydrodynamic delivery of naked DNA. Two days after injection liver samples were analysed for GFP fluorescence. The WT LDL receptor GFP protein was located on the cell surface whereas the W556S LDL receptor GFP protein was retained in intracellular compartments. Thus, the GFP-tagged LDL receptor protein allows both detailed time lapse analysis and evaluations in animals for the physiological modelling of mutations. This method should be generally applicable in functional testing of gene products for aberrant processing. PMID- 11781698 TI - Analysis of TSC2 stop codon variants found in tuberous sclerosis patients. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations. PMID- 11781699 TI - Polymorphism of trinucleotide repeats in loci DM, DRPLA and SCA1 in East European populations. AB - A normal polymorphism at three triplet repeat loci (myotonic dystrophy (DM), dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 1 (SCA1)) were examined in healthy unrelated individuals from the Siberian Yakut (Mongoloid) population, the Adygei (Caucasian) population and nine East European populations: populations from Russia (Holmogory, Oshevensk, Kursk, Novgorod, Udmurts, Bashkir), two Ukrainian populations (Lviv and Alchevsk) and one Belarussian. The distribution of alleles for DRPLA and SCA1 were similar for all East-European populations. For the DM locus, East European populations had typical allele distribution profiles with two modes, (CTG)5 and (CTG)11-14, but some differences were found for the Bashkir population where alleles containing 11-14 CTG repeats had relatively higher frequency. The Yakut population had different allele spectra for all types of repeats studied. Higher heterozygosity levels and insignificant differences between expected and observed heterozygosity were found for all tested loci. The latter led us to suggest that the trinucleotide repeat loci analysed are not influenced by selection factors and could be useful for genetic relationship investigations in different populations. PMID- 11781700 TI - Familial defective apolipoprotein B-100 in a group of hypercholesterolaemic patients in Poland. Identification of a new mutation Thr3492Ile in the apolipoprotein B gene. AB - The prevalence of the familial defective apolipoprotein B-100 (FDB) Arg3500Gln mutation in 525 unrelated hypercholesterolaemic Polish subjects was evaluated. DNA samples were screened for FDB mutation using SSCP method. Presence of mutation was confirmed using a mismatch MspI PCR strategy. Plasma lipid levels and clinical characteristics of 13 patients identified as carriers of the mutation and of their 23 affected relatives were analysed and compared with non affected ones. In the affected individuals a variable expression of lipid concentrations and of atherosclerosis symptoms were observed. The prevalence of FDB Arg3500Gln mutation in hypercholesterolaemic Polish subjects (3.7%) seems to be similar to the frequency reported in other Caucasian hypercholesterolaemic populations. The estimated prevalence of the mutation in general Polish population is relatively high being 1/250. The same haplotype at the apoB locus in the carriers of this mutation in Poland as in other populations from Western Europe suggests its common origin. In one hypercholesterolaemic subject a non hitherto described mutation was identified. It consisted in C-->T transition in apoB codon 3492 leading to threonine to isoleucine substitution in 3492 position of apoB gene (Thr3492Ile). PMID- 11781701 TI - Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the North and South of Portugal. AB - An earlier study of reference values of iron parameters in Portugal showed significant differences between populations from northern and southern villages. This study addresses the question of the geographical distribution in Portugal of the two main mutations (C282Y and H63D) of the hereditary hemochromatosis gene, HFE. For that purpose, a stratified sample of 640 anonymous dried blood spot samples was randomly selected from the major regions of Portugal: North, Center, Lisbon and the Tagus Valley, Alentejo and Algarve. Differences in the geographical distribution of these two mutations were observed thus confirming the presumed differences between the age of the two mutations which is compatible with the postulated Celtic/Nordic origin of the C282Y mutation. The finding of a significantly higher allelic frequency of the C282Y mutation in the North (0.058) than in the South (0.009) could also point to an effect of differential selective forces acting in the different geographical areas of the country. Data on archaeological, ethnographic and linguistic records and on the North/South distribution of Portuguese cattle breeds of European or African origin have also been reported. In addition to their interest for population genetics, the results represent a reminder of the need to take into account regional differences in the design of strategies for population screening of hereditary hemochromatosis. PMID- 11781702 TI - Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations. AB - Familial Mediterranean Fever (FMF) is a recessively inherited disorder, characterized by episodic fever, abdominal and arthritic pain, as well as other forms of inflammation. Some FMF patients present higher IgD serum levels, and it is not yet known whether such an elevation is related to specific genotypes or correlated with a specific phenotype. In order to evaluate the association between known FMF-related mutations and IgD levels in confirmed patients, as well as the correlation between those levels and the presence of specific clinical signs, genotypic analysis and IgD plasma measurements were performed for 148 Lebanese and Jordanian FMF patients. Most common mutational patterns were M694V heterozygotes (19%) and homozygotes (17%), and V726A heterozygotes (18%) and homozygotes (5%), with an additional 11% combining both mutations. Twenty-one patients had higher IgD levels (superior to 100 microg/ml). The risk for higher IgD levels was significantly associated with M694V homozygote status (OR = 6.25) but not with heterozygotic one (OR = 1). Similarly, the risk for higher IgD was also found with V726A homozygotes (OR = 2.2) but not with heterozygotes (OR = 1.05). The use of colchicine was not statistically associated with IgD levels. Clinically, hyper IgD was also found significantly associated with arthritis (OR = 18). Thus, homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use. Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis. PMID- 11781703 TI - Effect of misspecification of gene frequency on the two-point LOD score. AB - In this study, we used computer simulation of simple and complex models to ask: (1) What is the penalty in evidence for linkage when the assumed gene frequency is far from the true gene frequency? (2) If the assumed model for gene frequency and inheritance are misspecified in the analysis, can this lead to a higher maximum LOD score than that obtained under the true parameters? Linkage data simulated under simple dominant, recessive, dominant and recessive with reduced penetrance, and additive models, were analysed assuming a single locus with both the correct and incorrect dominance model and assuming a range of different gene frequencies. We found that misspecifying the analysis gene frequency led to little penalty in maximum LOD score in all models examined, especially if the assumed gene frequency was lower than the generating one. Analysing linkage data assuming a gene frequency of the order of 0.01 for a dominant gene, and 0.1 for a recessive gene, appears to be a reasonable tactic in the majority of realistic situations because underestimating the gene frequency, even when the true gene frequency is high, leads to little penalty in the LOD score. PMID- 11781704 TI - ATB(0)/SLC1A5 gene. Fine localisation and exclusion of association with the intestinal phenotype of cystic fibrosis. AB - The Na+-dependent amino acid transporter named ATB(0) was previously found to be located in 19q13.3 by fluorescence in situ hybridisation. Genetic heterogeneity in the 19q13.2-13.4 region, syntenic to the Cystic Fibrosis Modulator Locus 1 (CFM1) in mouse, seemed to be associated to the intestinal phenotypic variation of cystic fibrosis (CF). We performed fine chromosomal mapping of ATB(0) on radiation hybrid (RH) panels G3 and TNG. Based on the most accurate location results from TNG-RH panel, mapping analysis evidenced that ATB(0) is localised between STS SHGC-13875 (D19S995) and STS SHGC-6138 in 19q13.3, that corresponds with the immediately telomeric/distal segment of the strongest linkage region within the human CFM1 (hCFM1) syntenic region. Regarding to the genomic structure and exon organisation, our results show that the ATB(0) gene is organised into eight exons. The knowledge of the genomic structure allowed us to perform an exhaustive mutational analysis of the gene. Evaluation of the possible implication of ATB(0) in the intestinal phenotype of CF was performed on the basis of the functional characteristics of the encoded protein, its apparent relevance to meconium ileus (MI) and position in relation to the hCFM1 syntenic region. We have analysed this gene in samples from CF patients with and without MI. Several sequence variations in the ATB(0) gene were identified, although none of them seemed to be related to the intestinal phenotype of CF. Even though no particular allele or haplotype in ATB(0) appears to be associated to CF-MI disease, new SNPs identified should be useful in segregation and linkage disequilibrium analyses in families affected by other disorders caused by the impairment of neutral amino acid transport. PMID- 11781705 TI - Indication of linkage and genetic heterogeneity of asthma according to age at onset on chromosome 7q in 107 French EGEA families. AB - It is generally believed that an early age at the onset of disease is associated with a stronger genetic component. Our aim here was to investigate both linkage and genetic heterogeneity of asthma, the latter corresponding to different genotype relative risks of a putative linked gene according to age at onset of asthma. This analysis was conducted in 107 French EGEA families with at least two asthmatic siblings, considering 157 markers that were part of our previous genome screen, using the TTS (the Triangle Test Statistic) which has been developed to detect both linkage and intra-sibpair genetic heterogeneity. This test has been applied to 38 asthmatic sib-pairs discordant for age at the onset of asthma. To confirm the existence of genetic heterogeneity, we also used the predivided sample test (PST) which compares the IBD (identity by descent) distribution of marker alleles between asthmatic sib-pairs concordant (67) and discordant (38) for the age at onset. The cutoff point used for the age at onset was 4 years, the median age at onset in our sample of asthmatic sibs. Linkage and genetic heterogeneity for a region located on chromosome 7q (at 109 cM from pter) were indicated by both tests, TTS (P=0.005, P>0.5 after correction for multiple testing) and PST (P=0.0001, 0.015 after correction). These results suggest a genetic factor on 7q involved in asthma with genotype relative risks differing according to age at onset of disease. PMID- 11781706 TI - A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia. AB - We investigated the molecular basis of hyperekplexia (STHE), an inherited neurological disorder characterised by neonatal hypertonia and an exaggerated startle response, in a kindred and identified a novel missense mutation in the pore-lining M2 domain of the alpha1 subunit of the glycine receptor (GLRA1). Sequencing analysis of all exons of the GLRA1 gene revealed a G1158A base transition in affected, heterozygous patients. The base transition results in a valine to methionine substitution at codon 260 in the middle of the M2 transmembrane domain. The location within the M2 domain suggests for this substitution a likely role in altering ion channel properties. PMID- 11781707 TI - Evidence of a normal mean telomere fragment length in patients with Ullrich Turner syndrome. AB - Clinical and epidemiological studies suggest that premature ageing and increased morbidity and mortality is present in Ullrich-Turner syndrome. We studied telomere restriction fragment length (TRFL) in 30 women with Ullrich-Turner syndrome and 30 age-matched control women. All Turner women had the 45,X karyotype verified by karyotyping. We found no difference in the mean TRFL in the young age group (TS: 7011+/-521 vs C: 7285+/-917 bp, P = 0.3), or in the older age group (TS: 7357+/-573 vs C: 7221+/-621 bp, P = 0.6). In conclusion, our data suggest that Ullrich-Turner syndrome is not associated with excessive telomere loss, at least when studied in peripheral blood leucocytes, and thus quite different from other premature ageing syndromes. PMID- 11781708 TI - TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients. AB - A small proportion of patients infected with Helicobacter pylori or using non steroidal anti-inflammatory drugs (NSAIDs) develops peptic ulcer disease. Since family studies have shown the importance of the genetic background of the host in the development of gastric and duodenal ulcers, immunogenetic factors involved in the regulation of inflammation deserve further study. Polymorphisms in the genes encoding tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) have been shown to contribute to the severity of infectious disease. Our aim was to study four bi allelic polymorphisms in the TNF and LTA genes, which occur as five haplotypes, in patients with peptic ulcer disease. A total of 130 patients with duodenal ulcer, 50 with gastric ulcer and 102 ethnically-matched Spanish Caucasian healthy controls were studied. H. pylori infection was determined by invasive and non invasive tests. Odds ratios were obtained by logistic regression analysis. H. pylori was detected in 91.8% of peptic ulcer patients and in 73.3% of controls (P < 0.001). Patients with gastric ulcer had a lower frequency of the TNF-308 allele 2 and a higher frequency of the LTANcoI 2.2 genotype when compared with duodenal ulcer patients (P < 0.01 and P = 0.03, respectively). Carriers of haplotype TNF-I were more frequent in gastric ulcer patients (49%) than in controls (28%) (P < 0.05) and the haplotype TNF-E was significantly more frequent in duodenal ulcers than in gastric ulcers (27% vs 8.2%; P < 0.01). Logistic regression analysis identified haplotype TNF-I carrier status as an independent risk factor for peptic ulceration in H. pylori-infected patients (OR: 4.2; 95%CI: 1.7-10.2). These results suggest that TNF and LTA gene polymorphisms are related to the development of gastric and duodenal ulcer and may determine disease outcome in H. pylori infection. PMID- 11781709 TI - Unexpected and variable phenotypes in a family with JAK3 deficiency. AB - Mutations of the Janus kinase 3 (JAK3) have been previously described to cause an autosomal recessive variant of severe combined immunodeficiency (SCID) usually characterized by the near absence of T and NK cells, but preserved numbers of B lymphocytes (T-B+SCID). We now report a family whose JAK3 mutations are associated with the persistence of circulating T cells, resulting in previously undescribed clinical presentations, ranging from a nearly unaffected 18-year-old subject to an 8-year-old sibling with a severe lymphoproliferative disorder. Both siblings were found to be compound heterozygotes for the same deleterious JAK3 mutations: an A96G initiation start site mutation, resulting in a dysfunctional, truncated protein product and a G2775(+3)C mutation in the splice donor site sequence of intron 18, resulting in a splicing defect and a predicted premature stop. These mutations were compatible with minimal amounts of functional JAK3 expression, leading to defective cytokine-dependent signaling. Activated T cells in these patients failed to express Fas ligand (FasL) in response to IL-2, which may explain the accumulation of T cells with an activated phenotype and a skewed T cell receptor (TcR) Vbeta family distribution. We speculate that residual JAK3 activity accounted for the maturation of thymocytes, but was insufficient to sustain IL-2-mediated homeostasis of peripheral T cells via Fas/FasL interactions. These data demonstrate that the clinical spectrum of JAK3 deficiency is quite broad and includes immunodeficient patients with accumulation of activated T cells, and indicate an essential role for JAK3 in the homeostasis of peripheral T cells in humans. PMID- 11781710 TI - Epstein-Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFkappaB pathway. AB - Epstein-Barr virus (EBV) is associated with several human malignancies including Burkitt's lymphoma (BL), Hodgkin's disease (HD) and nasopharyngeal carcinoma. A variety of cytokines and receptors have been described to be activated by EBV. Here we show that the IL-2 receptor (IL-2R) alpha-chain, which is weakly expressed on normal resting lymphoid cells, is activated by EBV. Comparison of EBV-negative BL cell lines and their EBV convertants showed an enhanced CD25 expression in EBV-positive BL cells. Transient expression of the oncogenic virus protein latent membrane protein-1 (LMP1) in L428 Hodgkin's lymphoma cells and in Burkitt's lymphoma cells (BL2, BL41, BL30) cells leads to enhanced CD25 expression. Both C-terminal activating regions (CTARs) of LMP1 are involved in CD25 activation. Inhibition of LMP1-mediated NFkappaB enhancement by a constitutive repressive form of IkappaB-alpha resulted in decreased CD25 surface expression, indicating that NFkappaB is involved in CD25 gene regulation. Furthermore, LMP1-mediated CD25 activation was associated with enhanced levels of the soluble form of CD25 (sCD25) in L428 Hodgkin's lymphoma cells but not in BL cells. LMP1 associated enhanced expression of membrane CD25 and soluble CD25 may have immunomodulatory functions and could be involved in biology of EBV associated diseases. PMID- 11781711 TI - Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients. AB - This study describes the importance of mannose-binding lectin (MBL) variant alleles for systemic lupus erythematosus (SLE) and accompanying infections in a population-based cohort. MBL alleles were determined in 99 SLE patients recruited from a representative Danish region. Patients were classified according to the 1982 revised ACR criteria as definite SLE (D-SLE) (n = 77) fulfilling > or =4 criteria and incomplete SLE (I-SLE) (n = 22) with 0.99, respectively). A meta analysis of eight previously published studies suggested that the presence of MBL variant alleles confer a 1.6 times overall increased risk for D-SLE (P < 0.00001). MBL variant allele carriers had higher disease activity (SLEDAI-index) in a 2-year follow-up period (P = 0.02) and had an increased risk of acquiring complicating infections in general (P = 0.03) and respiratory infections in particular (P = 0.0006). Only in SLE patients fulfilling > or =4 ACR criteria an increased frequency of MBL variant alleles was found. MBL variant alleles were also associated with increased risk of disease activity and of complicating infections indicating that the MBL gene is an SLE disease modifier locus. PMID- 11781712 TI - Linkage analysis suggests a region of importance for multiple sclerosis in 3p14 13. AB - Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region. PMID- 11781713 TI - Identification of novel polymorphisms in the beta7 integrin gene: family-based association studies in inflammatory bowel disease. AB - Linkage studies from five groups worldwide have confirmed the presence of an inflammatory bowel disease susceptibility locus on chromosome 12q. Beta 7 integrin is a strong candidate gene within this region, and is involved in lymphocyte homing to the gut and retention of intra-epithelial lymphocytes. Monoclonal antibodies to beta7 integrin ameliorate colitis in animal models. We obtained genomic sequence for beta7 integrin, and screened all 16 exons and 1.7 kb of 5' promoter region for polymorphisms in 24 individuals. Fourteen single nucleotide polymorphisms were identified in total and, of these, two common (frequency > or =10%) intronic and two amino acid changing polymorphisms were assessed for potential disease associations. Data were available from 102 multiply affected inflammatory bowel disease families (affected sibling pairs) and 362 simplex (one affected proband) families containing 254 ulcerative colitis, 13 indeterminate colitis and 300 Crohn's disease trios (parents + affected child). No significant associations with any disease phenotype were found with the transmission disequilibrium test. Beta 7 integrin is unlikely to be involved in the genetic susceptibility to inflammatory bowel disease, and therefore future studies on chromosome 12 should focus on other positional candidate genes. PMID- 11781714 TI - Variations in the human CC chemokine eotaxin gene. AB - The CC chemokine eotaxin (CCL11) plays a major role in the recruitment and activation of eosinophils in allergic disorders. In the present study, we performed polymorphism screening of the coding and promoter regions of the eotaxin gene (SCYA11). A G to A single nucleotide substitution was detected at position 67, which resulted in a non-conservative amino acid change of Ala at position 23 to Thr (A23T) within the signal peptide. Two single nucleotide substitutions, ie, C to T at position -426 (-426C>T), and A to G at position -384 (-384A>G), were detected in the 5'-flanking regions. Significant linkage disequilibrium was observed between positions -426 and -384, and also between 384 and +67. No significant association was observed between these variations and susceptibility to asthma. PMID- 11781715 TI - Octamer proteins inhibit IL-4 gene transcription in normal human CD4 T cells. AB - The balance of Th1 (eg, interleukin-2 (IL-2)) and Th2 (eg, IL-4) cytokines produced by CD4 T cells markedly influences the outcome of the adaptive immune response. Although octamer transcription factor proteins increase IL-2 transcription in T cells, their role in IL-4 gene transcription remains controversial. We have previously shown and now confirm that the proximal octamer binding site of the human IL-4 promoter, which separates the two most proximal NFAT binding sites, is bound prior to, but not after, activation in vivo. Since these two NFAT sites are essential for optimal IL-4 promoter activity, this suggested that prior engagement by octamer proteins might prevent adjacent NFAT binding and inhibit IL-4 gene transcription. In support of this hypothesis, here we show that NFAT proteins are unable to bind to a combined octamer/NFAT site unless the octamer proteins are competed away. Moreover, activity of an IL-4 reporter gene mutated in the proximal octamer binding site is increased compared to the wild-type promoter in human peripheral blood CD4 T cells. In addition, over-expression of either Oct-1 or Oct-2 decreased wild-type IL-4 promoter activity, while increasing IL-2 promoter activity. No decrease in promoter activity was seen when Oct-1 or Oct-2 was over-expressed with the octamer-mutant IL-4 reporter gene. Thus, octamer proteins are candidates to promote a Th1 rather than Th2 pattern of cytokine gene expression by activated CD4 T cells. PMID- 11781716 TI - Three polymorphisms in the 3' UTR of the TRAIL (TNF-related apoptosis-inducing ligand) gene. AB - Screening of the TRAIL (TNF-related apoptosis inducing ligand/Apo-2L) gene revealed three single nucleotide polymorphisms (SNPs) in the 3' UTR at nucleotides 1525G/A, 1588G/A, and 1591C/T. Over 50 individuals from each of two populations, Caucasian and African Americans, were genotyped for these three polymorphisms and allele frequencies were determined. PMID- 11781741 TI - Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. AB - Optimal treatment of erectile dysfunction (ED) following radical prostatectomy remains a subject of much controversy and is a significant concern for prostate cancer patients requiring surgical intervention. Neural stimulation involving nitric oxide synthase (NOS) is a crucial aspect of the normal erection process. In this study NOS isoform interaction was evaluated to improve our understanding of molecular changes pertaining to erection post radical prostatectomy. Bilateral cavernous nerve (CN) resected and control adult male Sprague-Dawley rats were killed 7, 14 and 21 days after injury. RT-PCR, in situ hybridization, Western blot and immunohistochemical analysis were used to evaluate changes in NOS isoform expression and distribution. NOS-I protein was dramatically decreased after CN injury while NOS-III and NOS-II remained unchanged. A profound decrease in smooth muscle and endothelium was observed in the corpora. To our knowledge this is the first report of differential altered NOS isoform protein abundance under conditions which mimic radical prostatectomy. These results show the importance of maintaining at least partial innervation of the penis after surgical intervention and that endothelial and smooth muscle changes resulting from loss of innervation may account for the ED observed in prostatectomy patients. PMID- 11781743 TI - Perturbation of cell cycle regulators in Peyronie's disease. AB - Peyronie's disease is a fibromatosis of the tunica albuginea, characterized by development of a plaque consisting primarily of collagen. It has been suggested that trauma to the erect penis is the inciting event. More recent research has focused on the cellular events leading to the dysregulated wound healing and plaque formation. Previous work has shown chromosomal aneusomies and this combined with an increased S-phase in plaque derived cell cultures suggests a perturbation in the cell cycle in this condition. The p53 protein has been shown to be an important cell cycle regulator and pro-apoptotic factor. Aberrant p53 function leading to cell immortalization and proliferation has been implicated in several human malignancies. We hypothesized that abnormal p53 function may explain the high proliferative ability of fibroblasts derived from Peyronie's plaques. This study was undertaken to study the presence and function of p53 and its downstream elements (p21, mdm-2) in Peyronie's disease cell cultures. Plaque derived fibroblasts have been established in culture and characterized. These cells and control neonatal foreskin fibroblasts were subjected to 5 Gy of gamma radiation to induce DNA damage. After fixation, antibodies to p53 and its transcriptional elements were used to stain irradiated and non-irradiated cells and levels of p53, p21 and mdm-2 were quantified using combined immunofluorescence and flow cytometry. Non-irradiated plaque fibroblasts demonstrated the presence of p53, p21 and mdm-2 at baseline. In control foreskin fibroblasts no p53 or mdm-2 were detectable at baseline. In irradiated foreskin derived cells significant changes in all elements were demonstrated indicating a fully functional p53 pathway and cell cycle checkpoint system in these cells. In contrast, plaque-derived cells showed no such alterations in levels of cell cycle regulators following irradiation. This is highly suggestive of an aberration of the p53 pathway in plaque-derived fibroblasts. Peyronie's plaque-derived fibroblasts demonstrated stabilization and defunctionalization of p53 protein combined with appropriate responses of its transcriptional elements. These findings may explain the high cell proliferation rates in these cells and suggests a role for perturbation of the p53 pathway in the pathogenesis of Peyronie's disease. PMID- 11781742 TI - Decreased penile erection in DOCA-salt and stroke prone-spontaneously hypertensive rats. AB - Numerous etiological studies have established a positive clinical association between hypertension and erectile dysfunction. However, to date, the mechanism underlying this dysfunction remains to be established. In this study, we demonstrate the presence of erectile dysfunction in two rat models of hypertension, and hypothesize that increased vasoconstrictor signaling via Rho kinase contributes to the decreased erectile response. We found deoxycorticosterone-salt and stroke prone-spontaneously hypertensive rats to exhibit a decreased erectile response, recorded as intracavernosal pressure/mean arterial pressure (ICP/MAP) upon electrical stimulation of the major pelvic ganglion. As previously shown, inhibition of Rho-kinase activity by intracavernosal injection of the selective inhibitor, Y-27632, resulted in an increase in ICP/MAP. However, Y-27632 was significantly less effective at increasing ICP/MAP in the hypertensive as compared to normotensive rats. Additionally, intracavernosal injection of Y-27632 potentiated the voltage stimulated increase in ICP/MAP in both hypertensive and normotensive rats, but was less effective at potentiating the voltage-mediated erectile response in the hypertensive rats. Altogether, our data demonstrate a decreased erectile response in a mineralocorticoid and genetic model of hypertension, and suggest the role of increased cell signaling by Rho-kinase in the vasoconstrictor activity of erectile dysfunction associated with hypertension. PMID- 11781744 TI - Vasoconstrictors in erectile physiology. AB - The erectile response of the penis depends on a balance between vasoconstrictor agents which cause cavernosal smooth muscle to contract limiting blood inflow, and vasodilators which relax cavernosal smooth muscle leading to increased blood inflow and erection. This review emphasizes the role of vasoconstrictors in the penis and shows that both endothelin-1 (ET-1) and the alpha-adrenergic agonist, methoxamine (METHOX) exert strong vasoconstrictor actions in the cavernosal circulation. We recently reported the vasoconstrictor actions of exogenous ET-1 and METHOX to be mediated by the RhoA/Rho-kinase pathway in the cavernosal circulation. While it is widely held that the nitric oxide-cyclic GMP-protein kinase G (NO-cGMP-PKG) pathway mediates vasorelaxation and penile erection, the interaction between this pathway and the vasoconstrictor process remains to be fully elucidated. Our studies also have shown that, during erection, the vasoconstrictor action of METHOX and ET-1 are inhibited and that NO is likely responsible for this inhibition. We hypothesize that the NO-cGMP-PKG pathway controls erection by acting in two distinct ways-by lowering intracellular levels of calcium leading to vasorelaxation and by inhibiting Rho-kinase mediated vasoconstriction. PMID- 11781745 TI - Penile prosthesis implantation and infection for Sexual Medicine Society of North America. AB - Penile prosthetics have developed over the past three decades into an effective treatment for erectile dysfunction with high reliability and patient satisfaction rates. The morbidity of these devices is principally limited to mechanical malfunction and the most feared complication of prostheses infection. Most penile prosthesis infections are caused by gram positive skin contaminations such as Staphylococci. The signs and symptoms of these infections may be difficult to identify in early stages, but late infections may lead to tissue loss and poor prognosis for prosthesis replacement. Treatment of penile prosthesis infections is best carried out with a salvage technique including aggressive lavage and prosthesis replacement. The success of this technique is salvage of prosthesis and return to function in more than 80% of cases. While penile prosthesis infection continues to be a dreaded complication, early diagnosis and aggressive surgical treatment may salvage the majority of these implants. PMID- 11781746 TI - Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism. AB - PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities. PMID- 11781747 TI - Clinical approaches to women's sexual dysfunctions. AB - OBJECTIVES: (1) to delineate the female sexual dysfunctions; (2) to present methods of identifying and treating female sexual problems or concerns. PMID- 11781748 TI - Sexual dysfunction in the diabetic patient. AB - The incidence of diabetes mellitus is increasing at an alarming rate, and diabetic men already make up a quarter of the men in our own specific medically oriented population of erectile dysfunction. The incidence of sexual dysfunction in men with diabetes approaches 50%, and this is only slightly lower in diabetic women. Hypertension is a frequent risk co-factor, being seen between 40% and 60% of diabetics in the literature. Obesity and hyperlipidemia are other frequent co factors. Interestingly, these risk factors are the same as those for coronary artery disease. The final common pathway for most of these factors is endothelial cell dysfunction. PMID- 11781749 TI - Is smoking an independent risk factor for erectile dysfunction? PMID- 11781753 TI - Food intake patterns and body mass index in observational studies. AB - OBJECTIVE: To review studies of patterns of food intake, as assessed by diet index, factor analysis or cluster analysis, and their associations with body mass index or obesity (BMI/Ob). DESIGN: Systematic literature review MEDLINE search with crosscheck of references. STUDIES: Thirty observational studies relating food intake patterns to anthropometric information were identified and reviewed. Food intake patterns were defined using a diet index, factor or cluster analysis in 12, nine and nine studies, respectively. Measures of body mass were made concurrently with the diet assessment in all studies, and only in a few cases were the primary outcomes related to BMI/Ob. RESULTS: The food intake patterns identified could, in most factor or cluster analysis studies, be categorised as: (a) meat, fatty, sweet or energy dense foods; (b) vegetables, fruit, whole grain and low-fat foods; or (c) by high alcohol consumption. The diet indexes were designed to capture a high diversity and/or food combinations matching the recommendations. The relationships with BMI/Ob were inconsistent-ten studies found that intake patterns, which we categorised as fatty, sweet or energy dense were positively associated with BMI/Ob, while similar patterns in four other studies were negatively associated with BMI. The significant associations between diet index score and BMI/Ob were consistently negative, while the associations between factor scores or cluster membership and BMI/Ob were less clear in terms of food intake pattern. Men and women had similar food intake patterns, but food intake patterns were less often positively associated with BMI/Ob in women. In 11 studies, there were no significant associations between food intake pattern and BMI/Ob. CONCLUSION: This review showed that no consistent associations could be identified between BMI or Ob and food intake patterns, derived from diet index, factor analysis or cluster analysis. However, the heterogeneity of food intake patterns identified by such analyses and the lack of gold standards for the application of these techniques hampers consistent analysis of a relation between food intake patterns and health. PMID- 11781754 TI - Negative and independent influence of apolipoprotein E on C-reactive protein (CRP) concentration in obese adults. Potential anti-inflammatory role of apoE in vivo. AB - BACKGROUND: Obesity is frequently associated with an increase in the early inflammation marker C-reactive protein (CRP), insulin resistance and changes in lipoprotein metabolism. Increased CRP is known as an independent cardiovascular risk factor. Since the apolipoproteins (apo) E and CIII components of HDL are associated with reduced cardiovascular risk and since apoE has in vitro anti inflammatory effect, we have investigated the relationships between apoE, apoCIII (in apoB and non apoB containing lipoproteins) and CRP in obese adults. METHODS: The following parameters from 34 healthy obese fasting women (age 22-64 y, body mass index (BMI) 28-68 kg/m2) were measured: (1) ApoE and apoCIII, in total plasma, in apoB- (E LpB, CIII LpB) and non-apoB-containing lipoproteins (E LpnonB, CIII LpnonB); (2) CRP and cytokine secreted by adipose tissue (TNF-alpha and its soluble receptor TNFR2); (3) triglyceride, HDL-cholesterol, systolic blood pressure, diastolic blood pressure, waist and hip circumferences, insulin, glucose. HOMA, a marker of insulin sensitivity, and the ratio E/CIII in LpB and LpnonB were calculated. RESULTS: CRP was positively correlated with BMI (P<0.05), waist circumference (WC, P<0.05), triglyceride (P<0.05) and negatively correlated with apoE (P<0.01) and E LpnonB (P<0.05). Two multiple regression models including parameters related to CRP with a P<0.25 were run stepwise to assess their independent contribution to CRP concentration. In the first model (including BMI, WC, HOMA, insulin, triglyceride, apoE, E LpnonB), apoE was the best predictor of CRP (P=0.01) together with triglyceride (P=0.02) and BMI (P=0.08). The second model took into account E/CIII LpnonB ratio with the parameters included in the first model. In this second model, E/CIII LpnonB was the best predictor of CRP (P=0.007), explaining 39% of CRP variance. CONCLUSION: ApoE is strongly correlated with CRP and could have an anti-inflammatory effect in vivo in obese subjects. This correlation could be limited to LpnonB lipoproteins, depending on their apoE and CIII relative content. PMID- 11781755 TI - Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. AB - OBJECTIVE: To study whether an increase of plasma leptin concentrations, as observed in the case of increased body weight, is associated with an inflammatory state. SUBJECTS: Sixty-three healthy subjects with body mass index (BMI) ranging from 20 to 61 kg/m2. MEASUREMENTS: Plasma concentrations of leptin, the inflammatory parameter soluble TNF-alpha receptors (TNFR55 and TNFR75), the acute phase proteins lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), alpha-acid glycoprotein (AGP), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1) and the anti-inflammatory soluble Interleukin-1 decoy receptor (sIL-1RII) were measured. RESULTS: As expected, BMI correlated significantly with leptin (r=0.823, P<0.001), but also with all acute phase proteins, both soluble TNF receptors and PAI concentrations. After correction for BMI and sex, no significant correlation between leptin and the acute phase proteins was seen. Interestingly, however, leptin strongly correlated with both TNF receptors (r=0.523, P<0.001 for TNFR55 and r=0.438, P<0.001 for TNFR75). CONCLUSIONS: This study shows the development of a pro-inflammatory state with increasing body weight. The BMI independent relationship between leptin and both soluble TNF-receptors is consistent with a regulatory role for leptin in the inflammatory state in morbidly obese subjects. PMID- 11781756 TI - Gender differences in diurnal triglyceridemia in lean and overweight subjects. AB - AIMS: Increased fasting and postprandial triglyceridemia is one of the cardiovascular risk factors for patients with insulin resistance. Since triglyceride (TG) metabolism largely depends on gender, we have investigated diurnal TG changes in patients with and without overweight, focusing on gender differences. METHODS: Twenty-two males and 22 females with overweight (mean body mass index (BMI) 28.0+/-2.3 kg/m2) measured capillary TG concentrations at six fixed time points on three different days. Diurnal TG profiles were calculated as area under the capillary TG curves (TGc-AUCs). The control group consisted of 24 males and 21 females who were not overweight (mean BMI 22.4+/-1.5 kg/m2). Biochemical and anthropometric parameters associated with insulin resistance were measured. RESULTS: Lean males and lean females had comparable fasting insulin levels (6.9+/-2.6 and 8.1+/-4.7 mU/l, respectively), but females had a more favorable fasting lipoprotein profile when compared to males. Diurnal TG profiles were lower in lean females than in lean males (16.9+/-4.3 vs 20.3+/-5.7 mMh, respectively, P<0.05). Overweight males and females had comparable fasting insulin levels (10.3+/-3.4 and 12.1+/-4.9 mU/l, respectively), which were higher than in lean subjects. Overweight females also had a more favorable fasting lipoprotein profile compared to overweight males. Diurnal TG profiles were similar in overweight females and overweight males (31.1+/-15.6 and 32.9+/-13.2 mMh, respectively). Stepwise multiple regression analysis showed that in both males and females, waist circumference was the strongest determinant of diurnal TG profiles when fasting TG concentrations were excluded from the model (R2=0.49 for males and R2=0.33 for females). These results suggest that overweight resulted in a 'male diurnal TG profile' in females due to abdominal fat accumulation. CONCLUSION: Insulin resistance in overweight subjects partly mitigates the gender differences of fasting and postprandial TG metabolism. The significant positive association between diurnal triglyceridemia and waist circumference supports the view that especially abdominal fat associated with insulin resistance enhances postprandial lipemia. PMID- 11781757 TI - Enhanced glucose uptake into adipose tissue induced by early growth restriction augments excursions in plasma leptin response evoked by changes in insulin status. AB - OBJECTIVE: The study used a rat model of moderate protein restriction exclusively during fetal and early neonatal life, which has been established to cause intrauterine early growth retardation, to investigate possible association between adipocyte glucose utilisation and leptin secretion in vivo. DESIGN: These rats, termed early protein restricted, were transferred to a diet containing the standard amount of protein at weaning and remained on this diet til adulthood, at which time adipocyte glucose utilisation and leptin secretion was compared with that of age-matched controls. Insulin status was modulated by acute (2 h) insulin infusion at a constant rate (4.2 mU/min per kg) to elevate insulin to the high physiological range. Euglycaemia was maintained by variable glucose infusion. MEASUREMENTS: Glucose utilisation was measured in vivo in conscious unrestrained rats using 2-deoxy[1-3H] glucose. Leptin concentrations (measured by radioimmunoassay) and whole-body glucose kinetics (measured using [3-3H] glucose) were studied in the postabsorptive state and after acute insulin stimulation. RESULTS: Adipose-tissue glucose utilisation rates in vivo tended to be higher in the post-absorptive state and were consistently 1.8-3.0-fold higher after insulin stimulation in the early-protein-restricted group compared with the control group. Both the absolute increase in leptin concentration elicited by hyperinsulinaemia and the magnitude of the effect of insulin to elevate plasma leptin levels were greater in the early-protein-restricted group compared with the control group (by 2.2-fold and 1.6-fold, respectively). The effect of insulin to stimulate R(d) was much greater in the early-protein-restricted group (4.1 fold) than in the control group (2.2-fold) and the absolute increase in R(d) elicited by insulin was 43% higher in the early-protein-restricted group than in the control group. CONCLUSIONS: It is concluded that poor early growth enhances the acute leptin response to changes in insulin status through programmed changes in adipocyte glucose handling. PMID- 11781758 TI - Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality. AB - OBJECTIVES: To evaluate whether there is one central abnormality contributing to the conditions associated with the metabolic syndrome (MES), or whether one abnormality is contributing on multiple levels. METHODS: We recruited 145 Chinese subjects aged 17-68 y with varying degrees of insulin-sensitivity (IS): 33 healthy, 59 with type 2 diabetes mellitus, 32 essential hypertensives and 21 dyslipidaemics. IS was evaluated by the short insulin sensitivity test using a 0.1 U/kg intravenous bolus dose of insulin. Blood pressure, anthropometric measures and biochemical parameters associated with IS were also measured. Exploratory factor analyses (EFA) were performed in the entire group of 145 subjects and in the 76 with normal glucose tolerance. RESULTS: EFA in all 145 subjects defined three distinct, independent factors. Factor 1 was interpreted as general and central adiposity, impaired IS and glucose intolerance, Factor 2 was associated with hypertension and general and central obesity, whilst Factor 3 was strongly related to low HDL-cholesterol and high triglyceride concentrations and weakly to waist circumference. In patients with impaired glucose tolerance, only two factors were identified; factor 1 related to reduced IS, impaired glucose tolerance, dyslipidaemia and general and central adiposity, and factor 2 which was related to blood pressure and general and central adiposity. CONCLUSIONS: These models suggest that the clustering of variables in MES is a result of multiple factors linked by adiposity and not a single aetiology. Furthermore, increases in blood pressure are related to obesity in these Chinese subjects rather than decreased IS per se. PMID- 11781759 TI - Central obesity predicts the worsening of glycemia in southern Chinese. AB - AIMS: The association between obesity and type 2 diabetes has been found to be consistent across different ethnic populations. Our aim was to study the contribution of obesity to the development of type 2 diabetes in a non-obese Chinese population with a high prevalence of diabetes (9.8% in 1995-1996). METHODS: Six-hundred and forty-four non-diabetic subjects were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (1995-1996). This was a community-based population study which involved the use of a 75 g oral glucose tolerance test and 1985 World Health Organization diagnostic criteria. Their glycemic status was reassessed at 2 y. RESULTS: In subjects with impaired glucose tolerance (n=322), the annual progression rate to diabetes (4.8%; 95% CI 2.5 7.1%), was 8-fold that in control subjects (0.6%; 95% CI 0.0-1.4%; P<0.001). Baseline waist-hip ratio (WHR; OR per unit increase=1.05; 95% CI 1.02-1.07, P=0.0003) and post-load 2 h plasma glucose (OR per unit increase=2.02; 95% CI 1.76-2.34, P<0.0001) were significantly associated with glycemic status at 2 y in stepwise polytomous logistic regression analysis. Subjects with high baseline waist circumference or WHR (> or =median) were more likely to have worsening of glucose tolerance at 2 y than those with low waist circumference (60 treated for a variety of internal medical complaints in an acute geriatric hospital were examined with the help of comprehensive somatic diagnostics, the Impairment Score (IS), self evaluation scales and a semistructured biographical interview. 27.5% (n = 43) of the study participants were classified as cases of psychogenic illness. 22 (14.1%) of them fulfilled diagnostic criteria for depressive disorder. Depressive patients were physically more impaired, reported rare and less satisfying social contacts and different coping strategies than the other study participants. With regard to their biographical reconstructions, cases reported more experienced burden and less experienced support. In discrimination analysis, 78.4% of the study participants were correctly classified as cases vs. non-cases of psychogenic illness by one biographical variable and two coping strategies. Results are discussed as risk factors or protective factors for psychic health in old age considering their clinical relevance. PMID- 11781893 TI - [Not Available]. AB - The changing life conditions of elderly women and the increasing treatment of them requires a further explication of the psychodynamic conflicts, characterizing this developmental phase. Starting from the concept of ego ideal a difference between ego ideal and wishful seif is pointed. These two concepts mark a relevant shift, that is often experienced in the second half of life. This thesis is exemplified with a 59 year old patient. Last some considerations of psychotherapy treatment are pointed out. PMID- 11781894 TI - [Not Available]. AB - This contribution is aimed to put forward the theoretical position that general perceptions of stressfulness in the actual life Situation do not simply reflect concrete episodes, experiences and events, but are at least in part result of former coping processes, initiated to maintain or (re-)establish a personal satisfying perspective on life. In a first step we describe stressful episodes, experiences and events in the actual life Situation of 150 dependent old. In the following parts the relationship between an objective measure of stress and perceptions of stressfulness in actual life Situation, the impact of the quality of medical treatment and social Services on this relationship, and proposals for a possible improvement of medical treatment and social Services are discussed. Results do confirm our hypothesis that quality of medical treatment and social Services can be conceptualized as a personal resource buffering the impact of specific episodes, experiences and events on general perceptions of stressfulness. PMID- 11781895 TI - [Not Available]. AB - Facing the increasing number of single-parent-families we investigated the impact of fathers absence within the first six years of childhood on psychic/psychosomatic impairment in later life. We used data from the Mannheim Cohort Study on the Epidemiology of Psychogenic (neurotic spectrum) Disorders for a comparison of extreme groups with a favourable or bad course of clinical impairment. In adition we performed regression analysis of the long term course of clinical impairment for the total follow-up sample (mean follow-up intervall 11 years, N=301) with psychometric, clinical and childhood variables. The absence of the probands father (> six months within the first six years of life) was a significant independend predictor of clinical impairment in later life, accompanied by clinical and psychometric variables. A significant and increasing impairment existed even in 73 of 125 older probands (birth cohort 1935), who missed their father in early childhood. The sociopolitical implications of these findings are discussed. PMID- 11781896 TI - [Not Available]. AB - From the theoretical perspective of this contribution, analyses of psychological adjustment and coping in holocaust survivors should not only focus on the presence versus absence of diagnostic criteria of mental disorders. Coping with traumatic reminiscence in holocaust survivors is conceptualized as human behavior reflecting competences and resources as well as chances and limits of successful adjustment provided by life-long development and a given Status in society. On the basis of a clusteranalysis five pattems of coping are distinguished. The number of persons characterized by specific coping pattems indicates that most extermination camp survivors do possess effective coping abilities that allow them to establish or maintain a personal satisfying perspective on life. Coping pattems are influenced by biographical factors as well as by specific characteristics of reminiscence, health Status, social integration and financial resources. PMID- 11781897 TI - [Not Available]. AB - Theoretical issues and research emphasis within the field of attachment theory have shifted from attachment behavior "to the level of representation" (Bretherton, 1985) since the middle of the 80ies. The paper presents an overview on basic assumptions, research methodology and empirical findings in the field of attachment research. Four issues are addressed, which are relevant for psychosomatic research. These concern: (1) The prevalence of insecure attachment representation in psychosomatic disorders; (2) the association between insecure attachment representation and an increased psychophysiological reactivity; (3) the potential link between attachment and affect regulation and (4) the question, whether the classification of attachment representations may increase our understanding of specific aspects of illness behavior in psychosomatic conditions such as somatoform disorders. PMID- 11781898 TI - [Not Available]. AB - Infertility means psychological stress for both sexes if their wish to have a child remains unfulfilled. The way men cope with infertility is partly due to the psychodynamics of their motives for parenting. In the paper, these motives are analysed by a combination of statistical and qualitative methods (content analysis). 137 Patients addressing an andrological outpatient department were asked to fill in a questionnaire of their motives for parenting. A cluster analysis yielded a four cluster solution, two of them being contrary to each other. One was interpreted as characterising "ambivalence towards the child", the other as "child-dependent or offspring-fixated". This interpretation was validated by qualitative data drawn from content analyses of psychodynamic interviews performed with a subgroup of 80 andrological patients. The results do have clinical relevance; they allow to better understand the psychological and psychodynamic sequelae of male infertility thus providing some cues for specific therapeutic interventions. In addition, the study is of methodological interest, because of the combination of quantitative and qualitative empirical methods. PMID- 11781899 TI - [Not Available]. AB - Since the 70 years approximately 50 000 children have been born in the Federal Republic of Germany after artificial insemination by donor. The most studies of substantial collectives describe an inconspicious mental and emotional development of the children. However, due to examinations of Special cases, negative effects on the development of the children are expected as a result of the behaviour of social fathers to keep the insemination secret and to turn away from them. In a follow-up study six years after the treatment of insemination 22 successful couples of parents of originally 57 couples (before insemination) could be reexamined. They rated their children by a detailed interview, as well as by a variant of the repertory grid technique, which permits an estimation of object relations. Under an idiographic aspect, the use of the repertory grid technique made it possible to learn the individual meaning of the children to the respective couple. As a group examination it allowed generalizable Statements to judge the children in relation to the self-image of the parents. The major part of the parents judged their children as "close" to their seif and their self ideal. Any indication of retreat by social fathers could not be given. PMID- 11781900 TI - [Not Available]. AB - Endometriosis is one of the most frequent gynecological disorders in the reproductive age. Discrepancies between clinical findings and subjective Symptoms cause the question of the determing factors for the subjective experience. In the present study an hermeneutic, sense-orientated approach was employed by using qualitative methods of research. Eleven interviews with endometriosis patients were recorded on tape and transcribed, followed by an individual-case and a comparative analysis in partly deductively and inductively defined categories. The psychosexual development has been found as negatively influenced. Endometriosis patients show conflicting concepts of their sex-specific role. A found aggression conflict manifests itself in the pain Sensation, at an intrapsychic land an interpersonnel level: it influences the relations with other persons, in particular, the doctor-patient relationship. Changes of sense in the doctor-patient-relationship and recent concepts of psychosomatic disorders are discussed. PMID- 11781901 TI - [Not Available]. AB - Duodenal and gastric ulcers are associated with gastric Helicobacter pylori infection in 92% or 73% of the patients, respectively. Without eradication, the relapse rate after one year is about two thirds for duodenal ulcers and more than 50% for gastric ulcers. Successful eradication of Helicobacter pylori reduces the relapse rate to 0-6%. These data confirm the importance of an infectious agent in peptic ulcers. However, only of minority of Helicobacter pylori infected subjects develop an ulcer. Besides predisposing physical factors, chronic psychosocial stress is a weil documented ulcerogenic co-factor. Several interactions between stress and Helicobacter have been suspected to be involved in ulcer formation, and some of them are supported by preliminary empirical data. Acute psychological stress has also been associated with increased risk of gastric ulcers. Like a solely infectious concept, purely psychogenetic models of ulcer development as weil run the risk of reductionism. lnstead, every single patient needs individual assessment of infectious, somatic, and psychosocial risk. This biopsychosocial risk assessment offers the opportunity of individualized treatment, including psychotherapy in certain patients. However, the effect of individualized psychotherapy in ulcer treatment still needs to be evaluated in systematic intervention studies. PMID- 11781902 TI - Isolated fluid in the cul-de-sac: how well does it predict ectopic pregnancy? AB - We examined the risk of ectopic pregnancy among patients with isolated abnormal cul-de-sac fluid at transvaginal ultrasound. We conducted a retrospective cohort study of all ED patients presenting January 1995 to August 1999 with abdominal pain or vaginal bleeding and a positive beta-hCG test. The risk of ectopic pregnancy in patients with a moderate volume of anechoic fluid was compared with those with either a large volume of anechoic fluid or any echogenic fluid. Ectopic pregnancy was diagnosed in 16/38: 42%(95% CI 26%-59%) of patients with isolated cul-de-sac fluid, 5/23: 22% (95% CI 7%-42%) of patients with moderate amount of anechoic fluid, and 11/15: 73% (95% CI 45%-92%) of patients with a large volume of fluid or any echogenic fluid. These differences were significant (P =.005). Patients with isolated abnormal cul-de-sac fluid are at moderate risk for ectopic pregnancy. The risk increases if the fluid is echogenic or the volume is large. PMID- 11781903 TI - Variable diagnostic approach to suspected pulmonary embolism in the ED of a major academic tertiary care center. AB - The purpose of this study is to retrospectively examine the patterns of diagnostic modality utilization in the setting of suspected acute pulmonary embolism (PE) by physicians in the emergency department (ED) of a major academic tertiary care center. All patients (n=180) with a hospital discharge diagnosis of PE that were admitted through the ED during 1997 to 1999 were included. Overall test frequency and distribution, ancillary testing used when the initial ventilation-perfusion (V/Q) scan or spiral computed tomography (sCT) angiogram was nondiagnostic, concordance of V/Q and sCT, and sensitivities of D-dimer assays, arterial blood gas analysis, and deep venous imaging were assessed. There was a wide discrepancy in practice, most pronounced when first-line radiological studies were nondiagnostic. There was a poor correlation of PE detection between sCT and V/Q. D-dimer assay, arterial blood gas analysis, and deep venous imaging are insensitive tests for PE, and "gold standard" pulmonary angiography is rarely used. PMID- 11781904 TI - The "prudent layperson" definition of an emergency medical condition. AB - The study objectives, based on federal and state legislative language, were to objectively define symptoms and signs commonly agreed on by "prudent laypersons" as "emergency medical conditions." After comprehensive tabulation of symptom classifications from the International Classification of Diseases (ICD-9), we performed a survey of nonmedical laypersons. Data analysis included descriptive statistics, proportional calculations, and 95% confidence intervals. A minority of symptoms and signs (25/87, 29%) were considered emergency medical conditions by more than half of nonmedical survey respondents who were self-defined as prudent laypersons. The leading conditions deemed emergencies were loss of consciousness, seizure, no recognition of one side of the body, paralysis, shock, gangrene, coughing blood, trouble breathing, chest pain, and choking. Pain, except for renal colic or chest pain, was not considered an emergency. No symptoms or signs specifically related to gynecologic disorders were considered emergencies. Most symptoms and signs tabulated in the diagnostic coding manual, ICD-9, are not considered emergency medical conditions by self-designated prudent laypersons. These include many conditions that are commonly investigated and treated in the emergency department setting. Use of the prudent layperson standard for reimbursable emergency health services may not reflect the actual scope of symptoms necessitating emergency care. PMID- 11781905 TI - Geriatric trauma in the State of Illinois: substance use and injury patterns. AB - As the elderly population increases and they lead more active and healthy lifestyles, their exposure to the threats of injury multiply. Undoubtedly, the geriatric population will comprise a growing percentage of trauma patients. The role of alcohol and drug use in geriatric trauma has not been clearly defined. The purpose of this study is to determine the incidence of alcohol and illicit drug use in association with mechanism of injury in all elderly trauma patients presenting to level I and II trauma centers in the State of Illinois over 3 years. A retrospective analysis was performed on 3 years of data (January 1, 1994 to December 31, 1996), provided by the Illinois Department of Public Health as the Illinois Trauma Registry, which describes consecutive trauma patients presenting to level I and II trauma facilities in the State of Illinois. During the study period, there were a total of 134,846 trauma patient entries. Of these 32,382 (24.0%) were for patients 65 years of age or older. In those patients 65 and older, 1699 (5.2%) were tested for the presence of alcohol and 845 (49.7%) tested positive. Of the elderly patients who tested positive for alcohol, 71.8% were considered intoxicated (BAC >80 mg/dL). Urine toxicology screens were performed on 1785 (5.5%) elderly trauma patients, and 208 (11.6%) were positive. Besides alcohol, benzodiazipines and opiates were the most frequently detected drugs. For elderly patients under the influence of alcohol falls (49.5%) and motor vehicle crashes (36.7%) were the most common mechanism of injury. For geriatric patients testing negative for alcohol, motor vehicle crashes were a much more common mechanism of injury than falls (65.0% v 25.1%). Falls were a much more common cause of injury in elderly patients using alcohol than in those not using alcohol. Alcohol and substance abuse are possibly significant factors in geriatric trauma. Although only 5% of elderly trauma patients were tested for alcohol, nearly half had alcohol present on presentation to a trauma center, and the majority of these patients were intoxicated. Prospective studies are needed to determine the true incidence of alcohol use/abuse in the geriatric trauma population and the need for routine alcohol screening of these patients. Detection of alcohol abuse in elderly trauma patients could help identify individuals in need of counseling and rehabilitative treatment. It may also reduce future injuries in these patients. PMID- 11781906 TI - Evaluation of patient satisfaction and outcomes after assessment for acute ankle injuries. AB - Physicians argue that patient preferences influence their test ordering and their potential for compliance with clinical practice guidelines (CPG). This study was conducted to evaluate patient satisfaction with clinical practice in emergency department (ED) settings using a validated and widely publicized set of CPGs. Patients presenting to 4 hospital EDs were eligible if they had sustained acute ankle or foot injuries. All sites were involved with the dissemination of radiography CPG, and use of radiography was determined by treating physicians. Telephone follow-up was attempted for all patients who did not receive ankle or foot radiography (Group 1). A random sample of 25% of patients who had a normal radiograph interpretation (Group 2) was also chosen for follow-up. Structured telephone interviews were administered and included information on post-encounter health care utilization, subsequent radiography, and patient satisfaction. A structured questionnaire was administered to all ED physicians (N = 60) to elicit their perspectives on the clinical practice guidelines. In Group 1, 342 (69%) of 494 non-radiographed patients were successfully contacted. In Group 2, 623 (77%) of 812 patients with normal ED radiographs, were successfully contacted. After ED discharge, 86 (25%) Group 1 and 191 (31%) Group 2 patients had visited another physician within 2 weeks of the initial ED encounter (P =.07). Subsequent ankle radiography was similar between the groups (38 [11%] in Group 1 vs. 59 [10%] in Group 2; P =.38). Patients appeared to be similarly highly satisfied with physician care (P =.58) and with discharge instructions (P =.12) in both groups. Overall, 76% of physicians supported the use of CPGs; however, 78% reported that patient expectations influenced their application of the Ottawa Ankle Rules. This study suggests that patients are equally satisfied with care, access additional health care services similarly and obtain the same percentage of radiographs irrespective of the initial ED ankle/foot radiograph ordering. These results may help physicians in re-evaluating their perceptions that patient expectation influence utilization and have important implications in guideline development. PMID- 11781907 TI - Ability of paramedics to treat patients with congestive heart failure via standing field treatment protocols. AB - The objective of the study was to determine if paramedics can accurately select the appropriate standing field treatment protocol (SFTP) in lieu of on-line medical direction (OLMD) for patients with congestive heart failure. A prospective case series over 18 months determined the sensitivity and positive predictive value (PPV) of paramedics' treatment of CHF patients using SFTPs. All patients who were treated under the "rales" protocol and transported to our base hospital were evaluated for appropriateness of field treatment with correlation to discharge diagnosis. During this same time interval all patients ultimately diagnosed with CHF and treated by paramedics under any SFTP were studied. A total of 104 patients met the inclusion criteria with 102 available for analysis. Of the 58 patients treated under the rales protocol 50 (86%) had an ED diagnosis of CHF and 8 (13%) had a primary respiratory diagnosis. The remaining 44 (43%) of the 102 patients studied were treated under an SFTP other than rales but had a discharge diagnosis of CHF. Overall sensitivity for paramedics' correctly identifying CHF was 53%. Their PPV was 86%. In this study paramedics correctly identified only about half of the dyspneic patients who proved to have CHF, but their assessment of CHF did have a higher positive predictive value when this diagnosis was made. Further training and quality improvement efforts need to be directed towards improving paramedic performance with this challenging group of patients, with consideration given to requiring OLMD for patients presenting with rales. PMID- 11781909 TI - Contribution of ED admissions to inpatient hospital revenue. AB - Emergency department (ED) practices are traditionally profiled in terms of their patient encounters. Such evaluations reflect a preponderance of outpatient visits while crediting income from admitted patients to traditional hospital-based services. This study evaluates the contribution of ED admissions to inpatient hospital revenue. The study was set at an urban tertiary care community hospital with university affiliation. Information referable to ED patients was collected from the hospital's Universal Billing Code (UB-92)-based patient information warehouse. Data fields referable to hospital charges, insurance type, and disposition were used for analysis of a 1-year period from September 1, 1998 to August 31, 1999. Statistical analysis was through chi square and ANOVA. During the study period 33,174 patients were treated in the ED with 6,671 (20%) admitted to inpatient services. Total hospital charges for all ED patients during this time were $107 million dollars with $9.1 million (8.5%) generated from discharged patients and $98.0 million (91.5%) from admitted ED patients (P <.001). Mean charges for individual discharged patients were $344.10 whereas for individual admitted patients mean charges were $14,692.28. (P <.001) Medicaid and self pay represented 55.4% of the insurance coverage for discharged ED patients whereas these same insurance classes accounted for only 16.3% of admitted patients. (P <.001) Medicare visits accounted for 12.7% of discharged ED patients but 60.7% of admitted patients (P <.001). Total hospital gross revenue for inpatient services for the study period was $288 million of which 34% was contributed from admitted ED patients. ED services represent a major source of inpatient hospital revenue. The recognition of the ED's potential in this area may be lost if income from patients admitted through the ED is credited to traditional hospital-based services. PMID- 11781908 TI - Can specific patient variables be used to predict outcome of intracranial hemorrhage? AB - The study objective was to identify the demographic, physiologic, and anatomic variables associated with outcomes of patients with intracranial hemorrhages. We performed a prospective study of all patients with known or suspected intracranial hemorrhages transferred from a community hospital to the neurosurgical service of tertiary care centers in Toronto. Outcomes measured were patient disposition (admitted v discharged immediately), management (neurosurgical interventions v observation) and survival until discharge v death. Patient variables recorded pre- and post-transfer were analyzed using the statistical programs C.H.A.I.D. and C.A.R.T.(Answer-Tree Software, SPSS Inc.Headquarters, Chicago, IL). Two linear regression trees were constructed to reveal associations with each outcome. Sixty-seven patients between the ages of 24 and 89 were included in the study. Of these, 1 was referred for an epidural bleed, 20 for subdural bleeds, 21 for subarachnoid hemorrhages, and 25 for intracerebral hemorrhages. Thirteen of the patients in the study died or remained with permanent, severe neurological deficits. Of these, none had epidural hemorrhages, 4 had subdural hemorrhages, 5 had subarachnoid hemorrhages, and 4 had intracerebral hemorrhages. The linear regression tree constructed with C.A.R.T. revealed that the most important predictor of outcome was the GCS score of the patient on arrival at the neurosurgical center. Specifically, 71.43% of individuals arriving with a GCS score less than or equal to 7 died or remained with a severe neurological deficit, whereas only 5.66% of individuals arriving with a GCS score greater than or equal to 8 had such an outcome (P<.11). The regression tree constructed using C.H.A.I.D. revealed a similar result. Patients with a GCS score less than or equal to 5 on arrival at the neurosurgical center had a 70% chance of dying or remaining with a severe neurological deficit, whereas those with a GCS score greater than or equal to 13 had a 0% chance of having such an outcome (P <.0001). Furthermore, 100% of patients with post transfer GCS scores less than or equal to 5 and an absent gag reflex died or remained with a severe neurological deficit compared with only 25% of those with a GCS score less than or equal to 5 with an intact gag reflex (P =.0005). This study also revealed a number of incidental findings. The presence of bilateral unreactive pupils, absent corneal reflex or absent vestibulo-ocular reflex (dolls eye) independently predicted mortality in 100% of patients (not statistically significant). No patient with any of the following characteristics: any pupillary abnormality or age > 62 with a GCS < 5, achieved a normal functional outcome. Within the population of patients referred from community hospitals to a neurosurgical center for evaluation of intracranial hemorrhage, specific clinical findings are powerful predictors of mortality and poor functional outcome. Patients with a post-transfer GCS score <= 5 and an absent gag reflex had a 100% incidence of death or severe, permanent neurological dysfunction compared with only 25% of those arriving with GCS scores <= 5 with an intact gag reflex (P =.0005). Additionally, The presence of bilateral unreactive pupils, absent corneal reflex and absent vestibulo-ocular reflex independently predicted mortality in 100% of patients (not statistically significant). Other clinical findings including any pupillary abnormality and GCS <=5 combined with age => 62 negated the possibility of normal functional outcome (not statistically significant). These findings may have wide-ranging implications regarding the transfer and treatment of patients with intracranial hemorrhages, use of resources and counseling of families. PMID- 11781910 TI - Child safety seats: do doctors know enough? AB - The purpose of the study was to assess the knowledge of physicians in training about child safety seats and to test the effectiveness of a brief didactic session on improving that knowledge. Pre-post quasi experimental design was used. A 25-minute didactic session on the need for and appropriate use of child safety seats was presented. Subjects took a multiple-choice test before and immediately after the lecture. Tests were scored and baseline differences as well as differences in score improvements were analyzed by subgroup. Basic fund of knowledge was poor with a mean pretest score of 54%. Mean posttest score improved to 81.5% (P <.001). The only significant difference among groups was that pediatric residents had higher pretest scores (65%, P =.011), than their colleagues in other specialties. Medical students and residents in many specialties, including emergency medicine, have little baseline knowledge on the appropriate use of child safety seats. Knowledge can be improved with a brief didactic session. PMID- 11781911 TI - Reciprocal ST segment depression: impact on the electrocardiographic diagnosis of ST segment elevation acute myocardial infarction. AB - Acute myocardial infarction (AMI) is one of many causes of electrocardiographic ST segment elevation (STE) in ED chest pain (CP) patients; at times, the electrocardiographic diagnosis may be difficult. Coexistent ST segment depression has been reported to assist in the differentiation of non-infarction causes of STE from AMI-related ST segment elevation. The objective was to determine the effect of AMI diagnosis on the presence of STD among ED CP patients with electrocardiographic STE. Adult CP patients with electrocardiographic STE in at least 2 anatomically distributed leads were reviewed for the presence or absence of ST segment depression in at least 1 lead and separated into 2 groups, both with and without ST segment depression. A comparison of the 2 groups was performed in 2 approaches: all STE patients and then only with STE patients who lacked confounding electrocardiographic pattern (bundle branch block [BBB], left ventricular hypertrophy [LVH], or right ventricular paced rhythm [VPR]). All patients in the study underwent prolonged observation in the ED (at least 8 hours) with 3 serial troponin T determinations and 3 electrocardiograms (ECG). AMI was diagnosed by abnormal serum troponin T values (>0.1 mg/dL); electrocardiographic STE diagnoses of non-AMI causes were determined by medical record review. There were 171 CP patients with STE were entered in the study with 112 (65.5%) individuals show ST segment depression. When considering all study patients, ST segment depression was present at statistically equal rates in AMI and non-AMI situations (P = NS). The sensitivity, specificity, positive predictive value, and negative predictive value for the electrocardiographic diagnosis of AMI were 63%, 34%, 30%, and 67%, respectively. Patients with confounding patterns (LVH 46, BBB 19, and VPR 6) were removed from the analysis group, leaving 100 patients for analysis; 38 of these patients had ST segment depression. When considering this group of study patients, ST segment depression was present significantly more often in AMI patients (P <.0001). The sensitivity, specificity, positive predictive value, and negative predictive value for the electrocardiographic diagnosis of AMI were 69%, 93%, 93%, and 71%, respectively. Clinical diagnoses were as follows: 56 AMI, 50 USAP, and 65 noncoronary syndrome. When all CP patients with electrocardiographic STE are considered, the presence of ST segment depression is not helpful in distinguishing AMI from non-AMI. If one considers only patterns which lack electrocardiographic ST segment depression caused by altered intraventricular conduction, the presence of ST segment depression strongly suggests the diagnosis of AMI. In these cases, reciprocal ST segment depression is of considerable value in establishing the electrocardiographic diagnosis of STE AMI. PMID- 11781912 TI - A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. AB - In a recent case series, we reported that intramuscular droperidol appeared to be an effective therapy for the treatment of acute migraine headache. The objective of the study was to further assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. The study design was a randomized, clinical trial set in a community-based ED. The population was a convenience sample of ED patients who met International Headache Society acute migraine criteria. Exclusions included pregnancy, use of narcotic or phenothiazine medications within 24 hours. For the protocol, patients were randomized to 1 of 2 treatment groups. Patients and physicians were blinded as to the treatment provided. Patients recorded their initial pain on a 100mm Visual Analog Scale (VAS) Patients were randomized to receive either 2.5 mg droperidol intramuscularly; the other group received 1.5 mg/kg meperidine intramuscularly. After 30 minutes patients recorded their pain on the VAS and recorded their preference for the medication on a Likert Scale. Physicians recorded the incidence of any side effects and the need for rescue medication. Statistical analysis consisted of categorical variables that were analyzed by chi-square, continuous interval data by t-tests and ordinal data by Mann-Whitney U test. The primary outcome parameters were mean VAS score change and the percentage of patients who wanted to go home without rescue medication. The study had an 80% power to detect a 26 mm difference in the mean change in VAS between groups. Of the 29 patients who were enrolled, 15 received droperidol. Both groups were similar with respect to age (30.7 +/- 8.9 years droperdol v 32.7 +/- 9.9 years meperidine; P =.59), female sex (73% v 71%; P =.91), mean headache duration (24.7 +/- 28.3 v 18.3 +/- 25.8 hours; P =.55). The droperidol group had a higher mean initial VAS score (88 v 76 mm; P =.03). The 2 groups were similar with regard to outcome, including: mean change in VAS score (47 v 37 mm; P =.33), average Likert score (1.1 v 1.9; P =.85), and the percentage of patients who did not want rescue medication (67% v 57%; P =.61). The incidence of sedation was 6.7 v 14.3%. Akathisia occurred in 13.3% of pts who received droperidol. We found that intramuscular droperidol was similar in efficacy to meperidine with a low incidence of side effects. PMID- 11781913 TI - Serial electrocardiography. AB - During the past 15 years, medicine has witnessed several important advances in coronary artery reperfusion therapy for acute myocardial infarction (AMI). Both percutaneous transluminal coronary angioplasty (PTCA) and thrombolytic therapy have made significant advances in the early treatment of the AMI patient. Given both the shown benefit of these treatment modalities and the cardiac injury that they can prevent, it behooves the emergency physician (EP) to make a timely diagnosis of AMI to restore adequate perfusion and to salvage the maximum amount of myocardium. A correct diagnosis is dependent on EP expertise in the evaluation of the chest pain patient--in large part, the electrocardiogram. PMID- 11781914 TI - Orthopedic pitfalls in the ED: pediatric growth plate injuries. AB - Musculoskeletal injuries are frequently the reason children and adolescents seek care in the emergency department. In the skeletally immature patient, injury to the open growth plate can occur. When missed or mismanaged, these injuries can result in growth plate arrest. The emergency physician needs to remain vigilant for these injuries. This review article examines the clinical presentation, diagnostic techniques, and management options applicable to the emergency physician. PMID- 11781915 TI - Acute myocardial infarction presenting as subarachnoid hemorrhage. PMID- 11781916 TI - Massive intracerebral hematoma and extradural hematoma in amphetamine abuse. PMID- 11781917 TI - Preliminary results using the laryngeal tube for supraglottic ventilation. PMID- 11781918 TI - Dissecting aortic aneurysm presenting with unconsciousness. PMID- 11781919 TI - Transdermal fentanyl abuse and misuse. PMID- 11781920 TI - Ultrasound-guided reduction of a Spigelian hernia in a difficult case: an unusual use of bedside emergency ultrasonography. PMID- 11781921 TI - Dextromethorphan can produce false positive phencyclidine testing with HPLC. PMID- 11781922 TI - Primary epiploic appendagitis. PMID- 11781923 TI - Dientamoeba fragilis: a significant pathogen. PMID- 11781924 TI - Ovarian hyperstimulation syndrome: acute onset dyspnea in a young woman. PMID- 11781925 TI - Air in the spinal canal after skull base fracture. PMID- 11781926 TI - Acute aconitine poisoned patients with ventricular arrhythmias successfully reversed by charcoal hemoperfusion. PMID- 11781927 TI - Hemodialysis reversal of lithium overdose cardiotoxicity. PMID- 11781928 TI - Chemical burn misdiagnosed as brown recluse spider bite. PMID- 11781929 TI - The reticulocyte count: is it needed for evaluating typical sickle cell crisis presenting to the ED? PMID- 11781930 TI - A method for assembling a collaborative research team from multiple disciplines and academic centers to study the relationships between ECG estimation and MRI measurement of myocardial infarct size. AB - A method has been developed for establishing a "University Without Walls" for the purpose of studying the relationship between electrocardiographic estimation and magnetic resonance imaging measurements of myocardial infarct size. The research team includes faculty and students from 4 medical centers, with expertise extending from clinical to technical. Weekly interactive videoconferences provide the key research communication method. Study patients are recruited from 2 of the sites, and the correlations between their electrocardiographic and magnetic resonance imaging data are considered by the research team in conference. Outcomes of this program are both scientific publications in international peer review journals and formal postdoctoral degree attainment by the research trainees. PMID- 11781931 TI - A dynamic three-dimensional display of ventricular excitation and the generation of the vector and electrocardiogram. AB - Computer models, such as those produced by Solomon and Selvester, have helped increase our understanding of the heart's electrical activity. In the present report, we describe a dynamic three-dimensional computerized display of the myocardial excitation sequence that is based on this fundamental research. The display is based on the vectors of the potential differences generated in the various parts of the myocardium during its excitation. The sums of these individual vectors form composite vectors that are related to the ECG signals recorded from the body's surface. The display simultaneously portrays the temporal changes of the composite vectors in 3 dimensions and in each plane (the transverse, frontal and left sagittal). It also shows the corresponding changes in the QRS complexes in each of the 12 scalar ECG leads. The display shows the patterns of activation of the normal heart and an example of posterolateral myocardial infarction. The technique facilitates the understanding of myocardial activation and how it is modified by specific pathological conditions. It is believed that this method of presentation and visualization of the generation of the ECG will be of value in the teaching of this process. PMID- 11781932 TI - The grades of ischemia on the presenting electrocardiogram of patients with ST elevation acute myocardial infarction. AB - Patients with acute myocardial infarction who have terminal QRS distortion in addition to ST-segment elevation (grade III ischemia) on their presenting electrocardiogram have higher mortality and larger final infarct size than patients with ST-segment elevation without changes in the terminal portion of the QRS complex (grade II ischemia). This article discusses the data concerning the prognostic significance of the grades of ischemia on the presenting electrocardiogram and the possible underlying mechanism of terminal QRS distortion. Patients with grade III ischemia have more severe ischemia and faster progression of necrosis than patients with grade II ischemia. This might be related to less protection by "ischemic preconditioning" or presence of collateral circulation. PMID- 11781933 TI - Predictive value of T-wave morphology variables and QT dispersion for postmyocardial infarction risk assessment. AB - Different attempts have been made to use the 12-lead surface electrocardiogram (ECG) for risk stratification of patients prone to sudden cardiac death. Among others, QT dispersion (QTd) has been proposed as a simple risk marker, eg, in patients postmyocardial infarction (MI). To overcome the methodological limitations of QTd, novel T-wave morphology variables have been recently developed based on technologies that better quantify the substrate of a pathologically changed repolarization. In 280 post-MI patients with 27 events (death or nonfatal sustained ventricular tachycardia/ventricular fibrillation) during long-term follow-up (32 +/- 10 months), a 12-lead ECG was recorded before discharge and converted into a digital format. The prognostic value of digitally measured QTd and other conventional variables, and that of novel ECG variables of T-wave loop morphology was assessed. The latter included fully automatic and reproducible analysis of variables defining spatial and temporal T-wave variation as well as its wavefront direction. Among the 5 variables studied, the total cosine R to T (TCRT--describing the global angle between repolarization and depolarization orientations) and the T-wave loop dispersion were univariately associated (P = .0002 and P < .002) with events. Comparison of Kaplan Meier curves for patient strata above and below the median confirmed the strong discrimination of risk by TCRT and T-wave loop dispersion values (P < .003 and P < .001). On Cox regression analysis entering other univariately predictive risk stratifiers including age, left ventricular ejection fraction, heart rate, reperfusion therapy, beta adrenergic blocker treatment, and SDNN from Holter, TCRT (P < .03) yielded independent predictive value while T-wave loop dispersion was of borderline independence (P = .064). Heart rate (P < .02), left ventricular ejection fraction (P < .02), and reperfusion therapy (P <.02) also remained in the final model. In contrast, none of the conventional variables of repolarization dispersion including QTd and rate-corrected QTd revealed prognostic value on univariate or Kaplan Meier analysis despite optimized digital processing techniques. Computerized analysis of T-wave loop morphology from the 12-lead resting ECG permits independent assessment of post-MI risk and should replace the poorly conceptualized measurement of QTd. PMID- 11781934 TI - Current-density estimation of exercise-induced ischemia in patients with multivessel coronary artery disease. AB - Magnetocardiographic and body surface potential mapping data measured in 6 patients with multivessel coronary artery disease were used in equivalent current density estimation (CDE). Patient-specific boundary-element torso models were acquired from magnetic resonance images. Positron emission tomography data registrated with anatomical magnetic resonance imaging data provided the gold standard. Discrete current-density estimation values were computed on the epicardial surface of the left ventricle from difference (stress-rest) ST-segment maps. The ill-posed inverse problem was regularized with 3 different methods (Tikhonov regularization with an identity or a surface Laplacian operator and a maximum a posteriori estimator). Comparisons with positron emission tomography studies showed that the maximum a posteriori estimator is superior to other regularizations, provided that a suitable a priori information is available. In general, good correspondence was found for segments of high and low amplitude in current-density estimations, and the viable and scar areas in positron emission tomography, respectively. PMID- 11781935 TI - The role of heart rate in myocardial ischemia from restricted coronary perfusion. AB - Despite many years of study, certain aspects of myocardial ischemia remain incompletely understood. One observation that motivated this study is that acute, complete occlusion produces elevations but never depression of the ST-segment potentials in electrocardiographic leads over the ischemic zone. Limited flow, on the other hand, leads to ST-segment depression, both in in situ experiments and during clinical stress tests. The prevailing biophysical theory of ischemia suggests that complete occlusion should produce at least transient ST-segment depression, a finding we have neither observed in our own studies nor uncovered in the literature. Our goal with these experiments was to understand the difference between complete occlusion and reduced coronary flow, specifically the behavior at the transition between the two. We have performed experiments by using isolated dog hearts with a cannulated left anterior descending artery suspended in a human shaped electrolytic tank. To create a range of ischemic conditions, we changed coronary flow rates both suddenly and in controlled sequences and varied the heart rate of the isolated heart. The main finding was that in the isolated heart preparation, epicardial ST-segment depression over the ischemic zone arose only under conditions of combined restricted flow and elevated heart rate. Reduced coronary flow alone never produced ST-segment depression. These findings suggest that heart rate and probably metabolic work create the conditions necessary for subendocardial ischemia that reduced flow alone cannot provoke. They furthermore suggest that the degree of ST-segment depression for a given restriction in coronary flow may depend on heart rate, which supports the notion of rate correction for clinical stress electrocardiogram testing. PMID- 11781937 TI - Slow conduction in cardiac tissue: insights from optical mapping at the cellular level. AB - Under physiological conditions, slow conduction is essential for the function of the atrioventricular (AV) node, whereas, under pathophysiological conditions, slow conduction contributes importantly to the generation of life-threatening reentrant arrhythmias. This article addresses characteristics of slow conduction at the cellular network level during (a) a reduction of excitability, (b) a reduction of gap junctional coupling, and (c) in the setting of branching tissue structures. Microscopic impulse propagation in these settings was studied by using multiple site optical recording of transmembrane voltage in conjunction with patterned growth cultures of neonatal rat ventricular myocytes. In linear cell strands, a reduction of excitability slowed conduction by approximately 70% before block occurred. In contrast, critical reduction of gap junctional coupling induced a much higher degree of slowing (>99%) before block of conduction. Interestingly, a similar degree of conduction slowing was also observed in branching tissue structures under conditions of reduced excitability (98%). The finding of extremely slow but nevertheless safe conduction in these structures might be explained by a "pull and push" effect of the branches: by drawing electronic current from the activation wavefront, they first act as current loads which slow conduction at the branch points ("pull" effect). Then, on activation, they turn into current sources which feed current back into the system, thus supporting downstream activation and enhancing the safety of propagation ("push" effect). This "pull and push" mechanism may play a significant role in slow conduction in the AV node and in structurally discontinuous myocardium, such as the border regions of infarct scars. PMID- 11781938 TI - The ionic mechanisms of conduction in cardiac tissue. AB - Computer simulations are used to characterize conduction of the cardiac action potential under the following conditions: 1. Acute myocardial ischemia, 2. Reduced membrane excitability, 3. Reduced intercellular coupling, and 4. Propagation through inhomogeneous tissue structures. PMID- 11781939 TI - Changes in anisotropic conduction caused by remodeling cell size and the cellular distribution of gap junctions and Na(+) channels. AB - Because gene therapy presents a new frontier in the treatment of arrhythmias, it has become important to know how manipulation of the cellular distribution of proteins changes electrical events within individual cells, and whether these cellular changes affect conduction at the larger macroscopic size scale. However, experimental limitations in cardiac bundles prevent measurement of conduction delays across specific gap junctions, as well as the intracellular distribution of the maximum rate of rise of the action potential (V(max)). In view of these limitations, we used immunohistochemical morphological results as a basis to develop two-dimensional cellular models of neonatal and mature canine ventricular muscle in order to obtain insight into the electrophysiological effects of changes in the cellular distribution of proteins; eg, the major protein of cardiac gap junctions, connexin43. Morphological results showed that when the cells enlarged after birth, the gap junctions shifted from the sides to the ends of ventricular myocytes. At birth, V(max) was not different during longitudinal and transverse propagation. However, growth hypertrophy produced a selective increase in mean transverse V(max) with no significant change in longitudinal V(max). Two-dimensional cellular computational models of neonatal and mature ventricular muscle showed that the observed changes in the cellular distribution of the gap junctions and change in cell size accounted for the experimental results. The results unexpectedly showed that cellular scaling (cell size) is as important (or more so) as changes in gap junction distribution in determining the properties of transverse propagation. The results suggest that in pathological states that are arrhythmogenic, maintenance of cell size during remodeling the distribution of gap junctions is important in sustaining a maximum rate of rise of the action potential. PMID- 11781940 TI - Remodeling of cardiac gap junctions: the relationship to the genesis of ventricular tachycardia. AB - Cardiac gap junctions are responsible for normal conduction properties of the ventricles. Alteration in gap junction distribution (remodeling) in ischemic heart disease is likely to be an important cause of life threatening ventricular arrhythmias. PMID- 11781941 TI - PEDMEANS: a computer program for the interpretation of pediatric electrocardiograms. AB - The interpretation pediatric electrocardiograms (ECGs) is complicated because of the strong age-dependency of the diagnostic criteria. We wanted to develop and evaluate a computer program for the interpretation of pediatric 12-lead ECGs. Continuous age-dependent normal limits were established based on ECGs from 1,912 healthy Dutch children. Additionally, a reference interpretation was obtained for 1,718 ECGs recorded at the Sophia Children's Hospital. The total set of ECGs was divided in a training set of 1076 ECGs and a test set of 642 ECGs. All ECGs were recorded at a sampling rate of 1,200 Hz. Based on the normal limits and the training set, diagnostic rules were formalized in an iterative process by using expert interviews and automatic rule induction. The resultant rules were evaluated on the test set. The performance of the program, on our study population, appears to justify its use in a clinical setting. Preferably, the program should also be evaluated in other clinical centers. PMID- 11781942 TI - T-wave alternans in LQTS: repolarization-rate dynamics from digital 12-lead Holter data. AB - T-wave alternans (TWA) is a harbinger of ventricular vulnerability and an important prognostic indicator for torsade de pointes and likely sudden death in patients with LQTS. We analyzed the occurrence of TWA in 18 patients with LQTS (7 males, 11 females, ages ranging from 6 months to 32 years--median 8.4 years). Analysis was performed with software to investigate dynamics of cycle length mediated repolarization changes. Digital Holter ECG analysis revealed macroscopic, true TWA in 3 of 18 patients. TWA showed a variable morphological expression. One patient had continuous changes of T wave polarity, but not on a periodic beat-to-beat basis. Onsets of macroscopic TWA were preceded by long/short cycle length sequences and tachycardic rates above 130 to 140 bpm. Impact of ventricular premature beats on TWA onset was insignificant. Two of the identified patients with TWA had sudden cardiac death during follow-up (one refused PM therapy). At present, TWA cannot be detected automatically from Holter ECGs and therefore may be missed, despite the potential danger for the individuals. The observation that predominantly high beat rates and not beat rate changes, per se, triggered episodes of TWA renders difficult general therapeutic recommendations for the identified patients at risk. PMID- 11781943 TI - Optimal electrocardiographic leads for detecting acute myocardial ischemia. AB - This study identifies the most sensitive electrocardiographic leads for monitoring ST-segment changes caused by acute coronary ischemia. The data set consisted of 120-lead electrocardiograms (ECGs) digitally recorded during balloon inflation angioplasty in 3 groups of patients with single-vessel disease (left anterior descending [LAD], 32; right coronary artery [RCA], 36; left circumflex [LCx], 23). The ST deviation was measured in all recorded leads during baseline and ischemic states, and its difference between these 2 states (DeltaST) was calculated at 352 sites and plotted as DeltaST maps. The patients in each group were divided, by means of DeltaST criteria, into subgroups of "responders" and "nonresponders." Mean DeltaSTs for each group/subgroup were calculated and standardized by the corresponding standard deviation (SD); these values were plotted as mean DeltaST and t maps. Sites where extrema of DeltaST occurred most frequently were sought in bootstrap trials, performed in each group/subgroup. The results suggest that the optimal sites for the ischemia-sensitive leads are: V(3) (+) and just below V(8) (-) for LAD-related ischemia; the left iliac crest (+) and above V(3) at the third intercostal space (-) for RCA-related ischemia; and just below V(8) (+) and above V(2) at the third intercostal space (-) for LCx related ischemia. Three "optimal" bipolar leads using these sites registered, in the responders from the LAD, RCA, and LCx groups, mean DeltaST (+/-SD) of 232 +/- 59, 245 +/- 96 and 158 +/- 91 microV, respectively; the corresponding t values were 15.14, 9.90, and 6.75. In the 12-lead ECG, only lead V(3) approached optimal DeltaST and t values for the LAD responders (187 +/- 61 microV; t = 11.75) and lead III for the RCA responders (191 +/- 76 microV; t = 9.73), but even these values were significantly suboptimal (P = 0.0011 and P = 0.0120, respectively). We found that the "optimal" bipolar leads can be derived, to an excellent approximation, from the 12 standard leads or from 3 EASI leads (with 3 electrodes at Frank's transverse level and 1 on the manubrium), by using precalculated regression coefficients. By means of bootstrap trials, we estimated the mean sensitivity (SE) and the mean positive predictive value (PPV) with which 3 "optimal" vessel-specific leads could identify ischemia related to the LAD, RCA, and LCx arteries, in the test set, as (SE/PPV) 94.7/92.8%, 78.7/80.9%, and 81.5/80.9%. A similar diagnostic performance can be achieved by vessel-specific leads derived from the 12-lead ECG (93.0/93.4%, 76.6/82.0%, and 82.7/77.1%) and, interestingly, from the EASI lead system (97.8/88.4%, 78.0/80.2%, and 76.8/83.2%). Thus, although the "optimal" bipolar leads for detecting ischemia related to each of the 3 coronary arteries were found to require sampling outside the 12-lead ECG, these leads can be derived from the full set of 12 standard leads or--for clinical monitoring applications--from the EASI lead system by using fewer electrodes at convenient locations. PMID- 11781944 TI - T-wave morphology differences between patients with and without arrhythmic complication of ischemic heart disease. AB - The study investigated the differences in T-wave morphology between normal controls, patients with an uncomplicated follow-up after a myocardial infarction (MI), and patients with ischaemic heart disease and a history of ventricular tachycardia/fibrillation (VT/VF). The study population consisted of 164 healthy patients (age 53.4 +/- 18.7 years old, 80 women), 123 VT/VF patients (age 63.8 +/ 10.1 years old, 15 women), and 196 MI patients (age 59.2 +/- 10.0 years old, 23 women). In all patients, supine resting signal-averaged orthogonal electrocardiograms were obtained. After singular value decomposition of electrocardiogram signal, 2 T-wave morphology descriptors were calculated: total cosine R to T describing the global angle between repolarisation and depolarisation loops, and percentage of loop area expressing the irregularity of the T-wave loop (a more irregular wave results in a lower percentage of loop area value). Both parameters were practically uncorrelated (Controls: r = - .106, MI r = .161, and VT/VF r = .173) and different between individual groups of patients: total cosine R to T (Control vs. MI: P = 4.3 x 10(-8), Control vs. VT/VF: P = 2.7 x 10(-16), MI vs. VT/VF: P = 3.1 x 10(-6)), percentage of loop area (Control vs. MI: P = 0.07, Control vs. VT/VF: P = 1.1 x 10(-8), MI vs. VT/VF: P = 2.9 x 10( 5), all nonparametric Mann-Whitney test). The comparisons of cumulative histograms also revealed significant differences between all three groups for both parameters (Kruskal-Wallis ANOVA test). Thus, these numerical descriptors of T-wave morphology are powerful indicators of arrhythmic complications among patients with ischaemic heart disease. They also differentiate between patients with stable uncomplicated ischaemic heart disease and healthy controls. PMID- 11781945 TI - A real-time ST-segment monitoring algorithm for implantable devices. AB - Continuous ST-segment monitoring by implantable devices may lead to clarification of the substrate of arrhythmias, clarification of the origin of nonspecific chest pain, and titration or preventative application of established anti-ischemic therapies. Although ST-segment monitoring algorithms are available for surface electrocardiogram, the computational demand of algorithms for implantable devices must be minimized for considerations of device longevity. The new algorithm first locates a fiducial point (FPT) at the dominant peak of each QRS complex. The ST segment deviation (measured at 2 rate-adaptive delays after FPT, eg, FPT + 96 ms and FPT + 152 ms at 60 BPM) with respect to the isoelectric level (measured at the minimum slope preceding the QRS) is then measured. The following features are also quantified by simple operations: R-R interval, R-wave slope, R-wave amplitude, ST-segment slope, and noise content during the isoelectric segment. Inconsistencies in these features relative to their adaptive normal ranges are used to reject noisy or ectopic beats and sudden morphology changes. Finally, the ST-segment deviation over time is filtered to reject rates of change that are not likely attributable to human ischemia. Performance of the algorithm was evaluated on the European Society of Cardiology ST-T Database, which contains 180 hours of ambulatory electrocardiogram with 250 expert-annotated ischemic episodes. The sensitivity was 79% [74% 84%] (mean [95% CI]) and positive predictivity was 81% [76% 86%]. This performance is statistically equivalent to that of published electrocardiogram algorithms that were validated on the same dataset. Estimates of computational burden suggest that the algorithm could process two channels of electrogram continuously for more than 5 years with current implanted device technology. In conclusion, we have developed an algorithm for ST-segment monitoring that can be implemented in current implantable devices with sensitivity and positive predictivity that are comparable with the state-of-the art. PMID- 11781946 TI - Ablation strategies reflect evolving concepts of atrial fibrillation mechanisms. AB - Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice and results in the largest number of arrhythmia related hospital admissions. Despite the enormity of its impact on patients and the health care system, current medical therapy for AF is inadequate. Therapeutic approaches have been guided by understanding of fibrillation mechanisms. AF results from multiple simultaneous reentrant wavefronts. This is a diffuse and dynamic substrate with no discrete anatomic target. The catheter mediated "Maze" procedure employs creation of linear lesions to divide the atria into segments too small to support reentrant activation. Using current catheter technology this is a challenging procedure with low success rates and high complication rates. The observation that rapid focal firing of atrial myocytes within the pulmonary veins initiates fibrillation in the majority of paroxysmal AF patients has led to an entirely new ablation strategy. The sites of firing that initiate AF are targeted for ablation. Thus the paradigm for AF ablation has changed dramatically from altering the substrate of ongoing fibrillation to elimination of the triggers that initiate fibrillation. Initial experience revealed that multiple sites in the pulmonary veins are capable of rapid firing. Unfortunately not all sites fire during an ablation procedure. Sites that are quiescent during an ablation procedure may result in AF recurrence despite acute success. Ablation strategy has thus changed yet again to electrical isolation of all pulmonary venous tissue from the left atrium. The evolution of ablation strategies has paralleled our understanding of AF mechanisms. Elucidation of the mechanisms responsible for venous firing may lead to more specific therapy for the prevention of AF in the future. PMID- 11781947 TI - Functional anatomy of AV conduction: changing concepts in the ablation era. AB - Transitional cell populations (TCs) are located adjacent to the compact AV node in the rabbit. TCs located superior to the compact AV node and inferior to the interatrial septum (midpathway) have the longest Wenckebach cycle length (WBCL) (208 +/- 12 ms), but fail to determine AV WB when the posterior and/or anterior inputs remain intact. When all 3 TC populations remain intact, AV WB is determined at a shorter CL (195 +/- 15 ms) by TCs of the posterior input. With transection of the posterior TC input into the compact AV node, AV conduction is maintained at a longer AV WBCL consistent with WB within TCs located superior and anterior to the compact AV node. AV conduction remains intact in most hearts after transection of posterior and anterior TC populations from the compact AV node, with AV WB determined by TC input from the midpathway at a prolonged CL (214 +/- 10 ms) consistent with the pretransection midpathway WBCL. In a separate set of experiments, surgical separation of the 3 TC inputs from each other was performed while maintaining connection of the 3 individual TC inputs to the compact AV node remained intact. Stimulation of the proximal input from any 2 of the 3 TC inputs summated to produce a longer AV WBCL than observed from either AV nodal input alone. Data provided by the ablation of AV nodal inputs show the existence of 3 anatomically and functionally distinct populations of TCs providing independent and summated atrial input into the compact AV node. PMID- 11781948 TI - Effect of radiofrequency current on previously implanted pacemaker and defibrillator ventricular lead systems. AB - We compared the response of endocardial lead systems to radiofrequency (RF) current delivered during atrio-ventricular junction ablation (AVJA) for atrial fibrillation with uncontrolled ventricular rate in 107 patients. The mean age was 67 +/- 11 years and the mean ejection fraction 42 +/- 15%. Patients were divided into 3 groups based on the type of ventricular lead present at the time of ablation: a previously implanted defibrillator lead (group 3, n = 13), a previously implanted pacemaker lead (group 2, n = 46) or a temporary lead (group 1, n = 48), which was subsequently followed by a permanent lead implantation. During AVJA, a median of 5 RF applications (44 +/- 8 W) were given via 4-5-mm electrodes. All but 1 patient had right-sided lesions, while 6 patients also had left sided lesions. Ventricular pacing thresholds were evaluated immediately pre- and post-ablation at 24 hours and at 1 to 3 months. Increases in ventricular pacing voltage thresholds were noted in all 3 groups over time, with the greatest mean increase in group 3 patients: [table: see text]. A greater than 2-fold increase in pacing thresholds was observed only with previously implanted leads, usually within the first 48 hours. It occurred significantly more often in patients with group 3 (6/13 [46%]) compared to group 2 (6/46 [13%], odds ratio 7.6, P = 0.006). A progressive rise in pacing threshold required lead revision in 2/13 group 3 patients (15%) and 2/46 group 2 patients (4%). While RF current has only minor effects on pacing threshold in most patients with previously implanted ventricular lead systems, clinically important alterations requiring device reprogramming or lead revision may occur. Group 3 are significantly more vulnerable to RF current, though the mechanisms are unclear. Group 1 during AVJA, followed by permanent lead implantation appears advisable. Pts with a previously implanted group 3 who require AVJA should be monitored closely. PMID- 11781950 TI - Arrhythmogenic inherited heart muscle diseases in children. AB - The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure, leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device, or cardiac transplantation. In the majority of patients the origin is unknown, leading to the term idiopathic dilated cardiomyopathy. During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30% to 40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy, the genetic basis is beginning to unfold. To date, 2 genes for X-linked familial dilated cardiomyopathy (dystrophin, G4.5) have been identified and 4 genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In 1 form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators, and dystrophin cleavage play a role in the development of LV dysfunction. This review describes the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype. PMID- 11781951 TI - Long QT syndrome in children. AB - The long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval on electrocardiogram and a propensity to ventricular tachyarrhythmias, which may lead to cardiac events defined as syncope, cardiac arrest, or sudden death. Children are very frequently affected by LQTS accounting for about 50% of probands and 40% to 50% affected family members enrolled in the International LQTS Registry. LQTS probands stratified by age 0 to 5 years, 6 to 10 years, and 11 to 15 years showed that QTc is longer in the youngest group only when using Bazett's heart rate correction. However, when using Rautaharju's or Karjalainen's corrections, which adjust better for higher heart rate than Bazett's correction does, this difference is no longer present. Gender influences the risk of cardiac events in LQTS children with boys having significantly higher risk than girls by age 15 years, despite similar magnitude of QT prolongation. Genotype also influences clinical course of LQTS with LQT1 and LQT2 carriers having higher risk than LQT3 carriers. The risk varies by age among 3 genetic types of LQTS: LQT1 carriers are at higher risk of cardiac events between age 5 to 15 years than below age of 5 years, LQT2 carriers have the highest risk of cardiac events at age 10 to 15, and LQT3 carriers have infrequent cardiac events below age of 10 years. This pattern is observed in both boy and girl LQTS children. In conclusion, there is substantial age, gender, and genotype effect on the clinical course of LQTS children indicating the need of adjusting for those factors in clinical practice. PMID- 11781952 TI - Catecholamines in children with congenital long QT syndrome and Brugada syndrome. AB - Catecholamines have long been used as a provocative test in some forms of tachyarrhythmias including long QT syndrome (LQTS). In contrast, catecholamines are reported to decrease ST-segment elevation in leads V1-V3 in some patients with Brugada syndrome. Differential effects of catecholamines on QT interval, action potential duration, transmural dispersion of repolarization and Torsade de Pointes between LQT1, LQT2, and LQT3 forms of the LQTS were shown in experimental models of the LQTS by using arterially-perfused wedge preparations as well as in patients with congenital LQTS including children. In our preliminary result of patients with Brugada syndrome including a child, isoproterenol infusion was effective to decrease the ST-segment elevation in leads V1-V2 and to suppress the electrical storm of ventricular fibrillation. PMID- 11781953 TI - Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children. AB - Sudden cardiac death accounts for 19% of sudden deaths in children between 1 and 13 years of age and 30% of sudden deaths that occur between 14 and 21 years of age. The incidence of sudden cardiac death displays 2 peaks: one between 45 and 75 years of age, as a result of coronary artery disease, and the other between birth and 6 months of age, caused by sudden infant death syndrome. The role of cardiac arrhythmias in sudden infant death syndrome has long been a matter of debate and the role of cardiac arrhythmias in children in general is not well defined. Recent findings point to a contribution of primary electrical diseases of the heart including the Brugada and long QT syndromes to sudden death in infants and children. Mutations in SCN5A and HERG and KvLQT1 have been shown to be associated with life-threatening arrhythmias and long QT intervals in young infants. These mutations cause changes in sodium and potassium currents that amplify intrinsic electrical heterogeneities within the heart, thus providing a substrate as well as a trigger for the development of reentrant arrhythmias, including Torsade de Pointes (TdP), commonly associated with the long QT syndrome (LQTS). Mutations in SCN5A have also been shown to cause the sodium channel to turn off prematurely and thus to set the stage for the development of a rapid polymorphic ventricular tachycardia/ventricular fibrillation in patients with the Brugada Syndrome. In LQTS, ion channel mutations cause a preferential prolongation of the M cell action potential that contributes to the development of long QT intervals, wide-based or notched T waves, and a large transmural dispersion of repolarization, which provides the substrate for the development of TdP. An early afterdepolarization-induced triggered beat is thought to provide the extrasystole that precipitates TdP. In the Brugada syndrome, mutations in SCN5A reduce sodium current density, causing premature repolarization of the epicardial action potential due to an all or none repolarization at the end of phase 1. The loss of the action potential dome in epicardium, but not endocardium, creates a dispersion of repolarization across the ventricular wall, resulting in a transmural voltage gradient that manifests in the electrocardiogram (ECG) as an ST-segment elevation and in the development of a vulnerable window during which reentry can be induced. Under these conditions, loss of the action potential dome at some epicardial sites but not others gives rise to phase 2 reentry, which provides an extrasystole capable of precipitating ventricular tachycardia/ventricular fibrillation (or rapid TdP). The practical importance of identifying infants and children with Brugada and LQTS syndromes lies in the fact that most deaths due to these congenital defects can be prevented. A simple ECG is often sufficient to permit diagnosis and thus to prevent the development of life-threatening arrhythmic events. Mass ECG screening of neonates and children however has been the subject of debate focused on issues ranging from the emotional impact of dealing with false positives to those concerning socio-economic and medico-legal factors. These issues are discussed in other articles. These concerns notwithstanding, it is important that we continue to question whether the economic inefficiencies of current screening methodologies supersede the value of a young life. PMID- 11781954 TI - Some legal, social, and ethical issues related to the genetic testing revolution, as exemplified in the long QT syndrome. AB - Molecular Biology is revolutionizing medicine. There are a number of conditions, particularly exemplified by the long QT syndrome, where there is no structural abnormality but where a subset of patients is prone to sudden death. The issues of appropriate care are very complex, because there is tremendous overlap between patients with prolongation of the QT who remain asymptomatic and those with prolongation who are very symptomatic. Furthermore, even those who are prone to have one of the abnormal genes, may be asymptomatic. A large literature has developed, from both legal and ethical aspects, related to the fact that in genetic disease per se, not only is the person at risk, but so are many members of his or her family. A large literature has also developed as to which should be prime, the patient's privacy or the responsibility to make sure the entire family is knowledgeable and perhaps tested. At the present moment our care is based upon the fact that the precise identification of the gene is not yet available on a routine basis. This of course, may soon change. But we will still have difficult decisions to make. Obviously, we have a responsibility as physicians to be as precise as our discipline allows, but we have a responsibility to be flexible. Relief of anxiety, as an example, has to be a prime issue. This is certainly the case now when any information related to infants with potential sudden death is still incomplete. We must not approach the care of the patient in such a way that protection of the physician may interfere with appropriate care. The discussion necessarily includes a variety of aspects. PMID- 11781955 TI - From cell to body surface: a fully coupled approach. AB - Different types of equivalent cardiac sources are often used in the forward problem of electrocardiology. These may not be adequate to accurately reproduce the body surface potentials that are the result of cellular electrical activity, because they do not guarantee current conservation across the myocardial surfaces. Presented here are the outlines of 2 new coupling techniques that seek to overcome this problem by creating a continuous electrical pathway from the cellular level through to the body surface. The first technique directly couples the extracellular cardiac bidomain region to the surrounding passive torso regions creating a single system of equations without the need for matrix inversions. The second technique uses a fixed point iteration across each myocardial surface that has the goal of matching the potential fields and current flows across the cardiac boundaries into the neighbouring tissues. These techniques can be combined, directly coupling some regions and iterating across other region boundaries. Simulations on a transverse two-dimensional slice through a human male torso are presented, showing the convergence of these methods. PMID- 11781956 TI - Computer-assisted ECG interpretation for confirmation of premature atrial complexes. AB - Current programs for computerized ECG analysis are not interactive. We developed custom software for computer-assisted ECG interpretation that functioned interactively with an observer directing the computerized process. The software was first used for recognition of PACs superimposed on ST-T waveforms. The interactive process included 6 steps. 1) The computer displayed the 12-lead ECG and the user selected the most frequent QRS-T waveforms for averaging. 2) The computer generated and displayed the averaged QRS-T waveform. 3) The user selected waveforms suspected to have PACs superimposed on the ST-T segments. 4) The computer generated and displayed the difference waveform by subtracting the average waveform from the suspect waveforms. 5) The user recognized and p-waves in the difference waveform and marked the onset and offset by positioning the cursor and clicking. 6) The computer then measured p-wave amplitudes, durations, and areas and displayed the recognized p-wave. The program was developed using digital data from 2 ECGs and tested on 39 ECGs with suspected PACs and 26 control ECGs. RESULTS: The software and user interaction recognized 79 PACs in the suspect group. Control ECGs were analyzed using 3 complexes with the same leads and onsets as the test group. Of the 79 PACs found in the suspect group, mean values included an area under the curve of 4.0 +/- 3.2 microV-s for the test group versus 0.4 +/- 0.4 microV-s for the control (P < 0.001) and peak-to-trough voltage amplitudes of 104 +/- 66 microV versus 15 +/- 7 microV for the control (P < 0.001). The average time of onset of the premature complexes was 282 +/- 120 msec, and their duration was 100 +/- 28 msec. CONCLUSION: Custom software combined the superior human pattern recognition with the digital signal processing of the computer. This enhanced recognition of ectopic atrial activity. PMID- 11781957 TI - Automatic detection of artifacts in heart period data. AB - A major consideration before analyzing heart period data or RR intervals is the removal of artifact. Automatic artifact rejection becomes critical when analyzing huge data sets where manual inspection is impossible. This study developed an efficient, automatic algorithm which uses both a +/-20% criteria and the median of 25 surrounding RRs to set the boundary for a normal RR interval. The newly developed algorithm is compared with 5 previously developed artifact detection algorithms. Thirty minutes of simultaneous electrocardiogram and RR interval data from 10 infants of the Collaborative Home Infant Monitoring Evaluation (CHIME) study group are used to test the performance. Both real artifacts in the infant RR interval and fake artifacts are used to assess the performance of the algorithms. Sensitivity, specificity, and accuracy are used to quantify the performance. The newly developed algorithm performs better than other algorithms for detecting real artifacts in infant RR interval data, providing the best balance between sensitivity and specificity (73.46% and 99.17%, respectively), greatly improving specificity with only a slight loss in sensitivity. It works extremely well for detecting missing and extra beats (100% and 97.44% sensitivity, respectively) even on very noisy data. In terms of detecting fake missing beats and extra beats, high sensitivity is achieved in most situations, and there is not much difference in specificity among the algorithms. PMID- 11781959 TI - Correction of ECG variations caused by body position changes and electrode placement during ST-T monitoring. AB - BACKGROUND: Electrocardiogram variations (ECG) due to body position changes and electrode placements are common problems of continuous ST-T monitoring. Body position changes may cause QRS and ST-T changes and trigger false alarms. Placement of arm and leg electrodes in a coronary care unit environment is usually near the thorax instead of standard position at the wrists and ankles. This may affect the limb leads and complicate diagnostic interpretation. The purpose of this study was to assess the effects of these sources of ECG variation and to correct for them. Continuous 12-lead ECG recordings were obtained from 160 patients admitted to the coronary care unit. Each patient underwent a body position test (supine, left-lateral, and upright position). Scalar and spatial approaches were investigated for reconstruction of the ECG in supine position. The scalar approach uses linear regression. The spatial approach transforms the ECG into a derived vestorcardiogram. The spatial QRS-loop is then rotated and scaled to match the vector loop in supine position and transformed back to a 12 lead ECG. MATERIALS AND METHODS: To assess the effect of electrode placement, monitoring and standard limb leads were simultaneously recorded in a group of 80 patients. To map the monitoring leads to standard leads, general and patient specific reconstruction coefficients were derived by linear regression from half of the patients and tested on the other half. Similarity between the reference and reconstructed ECGs was measured by correlation, similarity coefficient [(SC=1 RMS(residual error)/RMS(signal)], and difference in frontal QRS-Axis. RESULTS AND CONCLUSION: Only 14% (23 of 160) of the patients showed marked ECG changes (ST elevations, QRS-axis shifts, T-wave inversions). The scalar method (median correlation > 0.994, SC > 0.902, QRS axis difference 0 degrees) performed better than spatial (median correlation 0.946, SC > 0.792, QRS axis difference 0 degrees). Monitoring leads can be mapped to standard limb leads in good to excellent approximaiton. General reconstruction (median correlation 0.993 and SC 0.764) performed slightly worse than patient-specific reconstruction (median correlation 0.997 and SC 0.908). PMID- 11781960 TI - Genesis of the T wave as based on an equivalent surface source model. AB - This article shows the use of the equivalent surface source model in its application to the genesis of the surface ECG in which the sources are of the double layer type. This model has previously been shown to yield an accurate description of body surface potentials during the QRS interval. Its application to the genesis of the T wave is now worked out in greater detail. In this source model, the full spatio-temporal character of the cardiac electric generator is expressed by means of an equivalent double layer situated at the boundary of ventricular tissue. The timing of local depolarization and of repolarization of the cells near this boundary is used to simulate the surface ECG. The background of this source model is discussed, as well as its validity. A matrix formulation is presented of the forward problem of computing the resulting body surface potentials. Based on this forward formulation, an inverse computation of the timing of the repolarization process was performed. Simulated T waves, based on this timing, showed a close correspondence with measured body surface potentials. By taking the inversely computed timing of repolarization as representing the true situation, the model can be used to study in which way perturbations in the timing of local repolarization effect the shape of T waves. An analysis based on this model indicates that the amplitude of the T wave is proportional to the dispersion of the repolarization times at the ventricular surface. The model is also shown to be capable of simulating the ECG changes during local ischemia. PMID- 11781961 TI - A new method to incorporate age and gender into the criteria for the detection of acute inferior myocardial infarction. AB - Recent studies have shown that younger women are more likely to die during and after hospitalization for acute myocardial infarction (MI) than older women and men of all ages. This may be partly due to incorrect diagnosis or late detection of acute MI in younger women. At high specificity levels (>98%), the sensitivity of the initial ECG to detect acute MI may be as low as 30% when using traditional criteria by both physicians and computerized interpretation programs. This study examines if women of different age groups have a similar ECG presentation to men during acute inferior MI and if the diagnostic accuracies of the initial ECG are comparable. We analyzed chest pain ECGs from Mayo Clinic and Medical College of Wisconsin, which included 1,339 patients with acute inferior MI and 1,169 age matched controls with noncardiac chest pain. We subdivided all groups by age (below and above 60 years) and compared ECG parameters (ST elevation, ST depression, QRS duration, R-wave amplitude, Q-wave duration and amplitude, QT interval) between genders. For inferior MI patients under age 60, women had lower ST elevations at the J point in lead II than men (57 +/- 91 microV vs. 86 +/- 117 microV, P < .02). This trend was reversed for patients over age 60 (lead a VF: 102 +/- 126 microV vs. 84+/-117 microV, P < .04; Lead III: 130+/-146 microV vs. 103+/-131 microV, P < .007). A neural network method was used to identify the most significant group of ECG parameters for detecting acute MI. An adaptive fuzzy logic method was developed for adapting to the threshold differences among the different gender and age groups. The new algorithm improved the sensitivity of acute inferior MI detection by more than 25% relative to old algorithm, while maintaining the high specificity around 98% for noncardiac chest pain patients. PMID- 11781962 TI - Age, sex, and the ST amplitude in health and disease. AB - Electrocardiograms (ECGs) from 1,338 apparently healthy adults were analyzed to calculate limits of normality of a variety of ECG measurements. A second set of ECGs from 503 healthy Chinese individuals was also available for comparison of selected normal ranges. It was found that the normal limits of the ST amplitude in healthy individuals decrease with increasing age and, in general terms, are lower in women than in men, particularly in the precordial leads. For example, the upper limit of normal ST amplitude in V3 in a 25-year-old man is 0.31mV but is only 0.11 mV in a woman of the same age. On the other hand, the age-dependent contribution to variation in the upper limit of normal of ST amplitude is effectively confined to men. The one exception to this appears to be the mean ST slope in V2, which decreases with increasing age in both men and women and is higher in the former compared to the latter. Recommended ECG related criteria, particularly in V1, for administration of thrombolytic therapy appear to be neither age nor sex dependent, which is a significant shortcoming given the foregoing information. PMID- 11781963 TI - Validation of advanced ECG diagnostic software for the detection of prior myocardial infarction by using nuclear cardiac imaging. AB - The investigators report the diagnostic performance of the latest version (Version 2.5) of the recently developed Cardiovise algorithm for detecting prior myocardial infarction (MI). The Cardiovise 2.5 prior MI algorithm, a component of Cardiovise Cardiac Diagnostic System (Inovise Medical, Inc, Newberg, OR), uses scalar QRS, scalar T wave, and vectorcardiographic QRS criteria for detecting, sizing, and localizing prior MI. In this study only the detection part of the algorithm's performance was evaluated, using 105 patients with and 98 patients without prior MI as indicated by the results of cardiac imaging with Sestamibi. The specificity, and sensitivity of Cardiovise 2.5 for detecting prior MI in this population of patients are 97% and 79%, respectively. The sensitivity and overall diagnostic performance of Cardiovise 2.5 was significantly better than those of a total of 6 human readers (3 cardiologists and 3 primary care physicians) and to 2 commercially available ECG diagnostic algorithms. PMID- 11781964 TI - Using 12-lead ECG and synthesized VCG in detection of right ventricular hypertrophy with terminal right conduction delay versus partial right bundle branch block in the pediatric population. AB - In pediatric electrocardiogram (ECG) analysis, mild right ventricular hypertrophy (RVH) and especially mild RVH with terminal right conduction delay (RVHtcd) are often confused with partial right bundle branch block (PRBBB). This is problematic for computer ECG analysis algorithms and even for most experienced pediatric cardiologists. This study was designed to achieve better classification of mild RVHtcd and PRBBB by combining the 12-lead synthesized vectocardiogram (VCG) transverse plane measurements with scalar ECG measurements. Pediatric ECGs used in the study were recorded with 15 leads and a 500 Hz sampling rate at the Lucile Salter Packard Children's Hospital, Stanford University Medical Center. Out of 4,200 ECGs collected consecutively over a period of 18 months, 447 RVH, 335 RBBB and 589 Normal were interpreted by expert pediatric cardiologists, and were included in the study. Statistical comparison of ECG and VCG measurements were done in stratified ECG sets (412) that have a visually indistinguishable waveform pattern, 117 RVHtcd, 96 PRBBB and 199 normal, showed significant differences in initial and terminal vectors in the transverse plane. The mean angle of the initial vector was anterior (57.2 degrees +/- 41.8) in the normal group, left anterior in the PRBBB group (34.4 degrees +/- 39.5) and in the RVHtcd group (31.9 degrees +/- 41.0) and. The mean angle of the terminal vector was right anterior (158.3 degrees +/- 36.8) in the PRBBB group, rightward (179.7 degrees +/- 29.9) in the RVHtcd group and right posterior (212.6 degrees +/- 37.8) in the normal group. These are clearly applicable features for a classification algorithm. Significantly improved classification results were obtained from a new algorithm using combined ECG and VCG measurements versus an existing algorithm. The limitation of this study stems from the unavailability of a more reliable gold standard. It may be necessary to used body surface potentials obtained with a large number of electrodes to accurately differentiate the study groups. PMID- 11781965 TI - Electrocardiographic measures of repolarization revisited: why? what? how? AB - Ventricular repolarization continues to be an enigma to clinical cardiologists and cardiac electrophysiologists. On the one hand, a century of experience has documented an association between abnormal T-wave morphology, QT prolongation and dispersion, T-wave alternans, and nonspecific ST-T waves with arrhythmia risk or negative prognostic outcome. On the other hand, recent advances in molecular electrophysiology have definitively implicated abnormal function and structure of cardiac ion channels associated with repolarization as primary arrhythmogenic mechanisms in long QT syndrome, Brugada's Syndrome, and idiopathic ventricular fibrillation and ventricular tachycardia. In spite of this extensive clinical experience and newly established mechanistic knowledge, robust measurements of repolarization and sensitive algorithms for reliable assessment of risk and prediction of arrhythmia occurrence have remained elusive. New insights into electrocardiographic waveform that reflect and capture the underlying spatial and dynamic characteristics of repolarization offer opportunity to devise clinical indices of repolarization that might be more predictive of risk or outcome than those currently used. Experimental and model data show evidence that the location and size of repolarization lesions may be deduced from T waveform. The changes of repolarization induced by altered activation sequence, and cycle length mediated alterations to repolarization offer additional means to assess the magnitude and significance of such lesions that are linked to increased arrhythmogenic risk. This article explores indices of repolarization that are sensitive to repolarization and its change and that provide opportunity to better characterize and assess repolarization for risk stratification. PMID- 11781966 TI - The Yosemite ISCE 2000 meeting experience: progress report for 2001 and future directions. Presidential address in Hutchinson Island 2001. PMID- 11781968 TI - A comparison of palatal adaptation in acrylic resin denture bases using conventional and anchored polymerization techniques. AB - PURPOSE: The study investigated the effects of palatal depth and a resin anchoring system on the adaptation of denture base resin to the master cast after compression molding and heat polymerization. MATERIALS AND METHODS: Forty-eight virtually identical polymethyl methacrylate dentures were fabricated on master casts with either a deep or shallow palatal vault. One half of the master casts of each palate type were altered by the addition of anchoring holes along the posterior land area, as well as perpendicularly in the midsaggital area. Anchoring holes were made with a #8 round bur to a depth of 5 mm. Twenty-four hours after polymerization, the bases on their casts were sectioned at the posterior border and evaluated for degree of adaptation using a traveling microscope. Maladaptation at the interface of the denture base and master cast was measured at predetermined mediolateral locations. A split-plot analysis of variance (alpha = 0.05) was performed followed by a post-hoc Dunn Multiple Comparison Test. RESULTS: In general, depth of the palatal vault did not significantly influence denture palatal discrepancy (p =.0780), but the use of the anchoring system significantly reduced mean gap distances (p =.000). At lateral and midpalate locations, gap distances between the denture bases and their casts were reduced from approximately 0.3 mm to approximately 0.1 mm when the anchoring system was used. CONCLUSIONS: Mean gap distances for steep palate dentures were significantly less than shallow palate dentures at vestibule and lateral palate locations, and anchoring holes placed in an edentulous master cast along the posterior land area and at the midline significantly improved the adaptation of denture bases. PMID- 11781969 TI - Color stability of provisional restorative materials after accelerated aging. AB - PURPOSE: Color of 11 provisional restorative materials (4 acrylic resins and 7 resin composites) was evaluated by reflection spectrophotometry immediately after fabrication, after aging for 15 kJ/m(2), and after aging for 60 kJ/m(2) to determine relative color stability under experimental aging conditions. MATERIALS AND METHODS: Specimens of provisional restorative materials were polymerized according to manufacturers' instructions and aged in an artificial aging chamber with exposure to a total ultraviolet irradiation of 60 kJ/m(2) in increments of 15 kJ/m(2). Color was measured by CIE L*a*b* on a reflection spectrophotometer before and after aging. Color change (Delta E*) was calculated and analyzed statistically by analysis of variance with repeated measures after 15 and 60 kJ/m(2) intervals of aging. RESULTS: Statistically significant changes in color were observed after accelerated aging at both the initial and final aging intervals. Five of the 11 provisional materials tested showed perceptible color change (Delta E* from 3.6 to 9.3) after accelerated aging of 15 kJ/m(2). Seven of the 11 provisional materials tested showed perceptible color change (Delta E* from 3.4 to 9.4) after accelerated aging of 60 kJ/m(2). CONCLUSIONS: Clinically perceptible color changes (Delta E* Delta 3.3) can be expected in some acrylic resin and composite resin provisional materials after accelerated aging. PMID- 11781970 TI - A comparison of 3 alloy surface treatments for resin-bonded prostheses. AB - PURPOSE: The most frequent cause of clinical failure of resin-bonded fixed partial dentures is a debonding at the metal-cement interface. The purpose of this in vitro study was to compare the tensile bond strengths of 3 different alloy-surface treatments when cemented to human enamel with a resin cement. MATERIALS AND METHODS: Cylinders of a nickel-chromium-beryllium (Ni-Cr-Be) and a gold-palladium (Au-Pd) alloy were fabricated and assigned to different surface treatment groups as follows: Group 1: Ni-Cr-Be, chemically etched; Group 2: Au Pd, airborne particle-abraded and tin-plated; and Group 3: Au-Pd, airborne particle-abraded and treated with the Alloy Primer (Kuraray Co, LTD, Osaka, Japan). The cylinders were bonded to the enamel surfaces of extracted, human third molars and stored in normal saline at 37 degrees C for 48 hours. The tensile bond strength of 21 specimens from each group was measured on a Universal Testing Machine (Instron, Canton, MA). Three failed specimens of each group were evaluated using scanning electron microscopy and energy dispersive spectroscopy. RESULTS: Statistically significant differences (p <.05) were found between all 3 treatment groups. The mean tensile bond strengths (+/- the standard error of mean) recorded as follows: Group 1: 10.6 MPa (+/-1.3), Group 2: 0.9 MPa (+/-0.2), and Group 3: 13.4 MPa (+/-1.0). Specimens from groups 1 and 3 revealed a trend towards mixture of cohesive, within the resin cement, and adhesive failures at the metal-cement interface. Group 2 specimens exhibited primarily adhesive failures at the metal-cement interface. CONCLUSIONS: The tensile bond strength of Au-Pd alloy specimens was significantly increased with the Alloy Primer. PMID- 11781971 TI - Analyzing the etiology of an extremely worn dentition. AB - Patients requiring extensive restorative care frequently exhibit significant loss of tooth structure. Specific clinical findings in an extremely worn dentition may vary widely and are often confusing. Severe wear can result from a mechanical cause, a chemical cause, or a combination of causes. The location of the wear, the accompanying symptoms and signs, and information gained from the patient interview are essential components in determining the etiology. A diagnostic decision tree facilitates a systematic analysis and diagnosis of dental wear. PMID- 11781972 TI - Fabricating a provisional restoration for a 2-stage, single-tooth implant with less than optimal angulation. AB - A technique is presented for fabricating a provisional restoration for a buccally angulated implant. This technique describes the fabrication of a provisional restoration for a labially angulated implant. This technique helps the prosthodontists to achieve esthetics and soft-tissue health until the definitive restoration is available. PMID- 11781973 TI - A new device to improve cast articulation procedures. AB - Achieving accurate cast articulation is a challenge for dentists and dental technicians. To ensure accuracy, a convenient, efficient, and predictable technique is needed to stabilize dental casts together, even when the casts are wet. The purpose of this article is to describe the use of a device specifically designed to secure casts together during the articulation process. PMID- 11781974 TI - The history of articulators: from facebows to the gnathograph, a brief history of early devices developed for recording condylar movement: part I. PMID- 11781977 TI - Heparin-binding EGF-like growth factor is present in human amniotic fluid and breast milk. AB - BACKGROUND/PURPOSE: Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) family that has been implicated in the healing of various organ injuries. Endogenous HB-EGF production is upregulated in response to injury to the kidney, liver, brain, skin, and intestine. Exogenous administration of HB-EGF protects against intestinal epithelial cell apoptosis and necrosis and intestinal ischemia/reperfusion (I/R) injury. This study examines the presence of endogenous HB-EGF in human amniotic fluid and breast milk, fluids that are in intimate contact with the developing and neonatal gastrointestinal tract. METHODS: Breast milk samples were collected from lactating women and amniotic fluid was gathered from full-term uteri (cesarian sections) or preterm uteri (amniocentesis). Crude and partially purified breast milk and amniotic fluid samples were analyzed for HB-EGF levels using an HB-EGF specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis results showed detectable HB-EGF levels in human amniotic fluid and breast milk, ranging from 0.2 to 230 pg/mL. Breast milk and amniotic fluid subjected to heparin affinity or HB-EGF-affinity column chromatography showed bioactivity eluting at positions consistent with those known for native HB-EGF. CONCLUSIONS: This study represents the first report of detectable HB-EGF in human amniotic fluid and breast milk. The presence of HB-EGF in these fluids may serve a role in the development of the gastrointestinal tract in utero, and in protection against gut mucosal injury after birth. PMID- 11781978 TI - Delayed institution of extracorporeal membrane oxygenation is associated with increased mortality rate and prolonged hospital stay. AB - BACKGROUND/PURPOSE: Severe meconium aspiration syndrome (MAS) is a frequent indication for extracorporeal membrane oxygenation (ECMO). Trials of less invasive cardiopulmonary support may result in fewer infants treated with ECMO but could delay institution of ECMO. The authors hypothesized that those infants with severe MAS who are treated with ECMO early will have a lower mortality rate and a shorter hospital course than those who receive delayed ECMO. METHODS: A retrospective review of all patients with MAS in the national extracorporeal life support (ELSO) registry for the decade 1989 through 1998 was performed. Data from the ELSO registry were examined for demographics, clinical parameters, and treatment course. Patients were divided into 3 groups based on the time from birth to institution of ECMO: group 1, 0 to 23 hours; group 2, 24 to 96 hours; and group 3, greater than 96 hours. These groups were compared for survival, duration of extracorporeal support, and duration of ventilatory support after ECMO. Statistical relevance was determined by analysis of variance (ANOVA) and Tukey's post-hoc test. RESULTS: A total of 3,235 of 4,002 patients with MAS had complete information on duration of mechanical ventilation. Overall mortality rate was 5.8%. The mortality rate in group 1 (n = 1,266) was 4.8%, group 2 (n = 1,568) 6.0%, and group 3 (n = 401) 7.7%. An increased time to ECMO was associated with a significant increase in mortality rate (P <.05). This also was associated with significant increases in the length of the ECMO run (157 +/- 4 v 130 +/- 2 hours, P =.02) and duration of post-ECMO ventilation (157 +/- 17 v 118 +/- 3 hours; P <.001). Those patients in groups 1 and 2 who did not respond to a trial of high-frequency oscillatory ventilation had significantly longer ECMO runs (129 +/- 2 v 113 +/- 1 hours; P =.001) and longer post-ECMO ventilator courses (137 +/ 2 v 114 +/- 1 hours; P =.002) than those who did not. CONCLUSIONS: Delay in institution of ECMO for MAS results in prolonged ECMO and need for post-ECMO ventilation. Consideration should be given to instituting ECMO earlier in patients with severe MAS. PMID- 11781979 TI - Pulmonary effects of in utero tracheal occlusion are dependent on gestational age in a rabbit model of diaphragmatic hernia. AB - PURPOSE: The authors investigated the effect of gestational age on lung development and maturation after in utero tracheal occlusion (TO) in a rabbit model of congenital diaphragmatic hernia (CDH). METHODS: In 46 fetal rabbits, CDH was created at 23 days' gestational age (GA; term, 31 days), corresponding to the pseudoglandular phase of lung development. A second intervention was performed at either 26, 27, or 28 days on 6 fetuses in each GA group. At that time, either TO (CDH + TO), or a sham operation (CDH + sham) was performed. Nonoperated littermates served as internal normal controls (CTR). All fetuses were delivered by cesarean section at 30 days GA to assess lung response by lung-to-body-weight ratio, pulmonary morphometry, and the density of type II pneumocytes. RESULTS: After TO, the lungs were significantly larger than in CDH animals; their weight was proportional to the duration of TO. Pulmonary morphometry in TO fetuses was comparable with that of controls. The density of type II cells was inversely related to the gestational age at which TO was performed, with normal values with TO at GA at 28 days. CONCLUSION: Timing of TO is critical to subsequent pulmonary development: early in gestation TO leads to pulmonary overgrowth and type II pneumocyte depletion, whereas normal values are obtained when TO is delayed till 28 of 32 days. PMID- 11781980 TI - Ex vivo testing of a temperature- and pressure-controlled amnio-irrigator for fetoscopic surgery. AB - BACKGROUND: Currently, amnioinfusion fluids used in operative fetoscopy usually are preheated to body temperature. As the complexity of procedures increases, purposed designed devices should be designed that allow control of pressure and temperature during amnioinfusion or amnioexchange. In the current study, a prototype amnio-irrigator and fluid heater were evaluated. METHODS: The medical fluid heater heats fluid by conduction up to 37 degrees C. The maximum irrigation pressure and flow rates can be preset. Actual irrigation pressure (0 to 30 mm Hg) and flow rate (0 to 300 mL/min) can be read on the front panel. A series of ex vivo experiments were set up to determine the relationship between the flow rate (FR) and lumen of the instruments as well as the maximum flow rate (MFR) with and without the pressure control. Further, the relationship between FR and the irrigation pressure (IP) was determined. In an artificial pseudoamniotic sac the relationship between FR and change in temperature was measured, with and without the use of the medical fluid heater. RESULTS: When the IP was limited to 24 mm Hg, FR and pressure were correlated (r = 0.34; P <.001). The larger the functional lumen of the fetoscopic instrumentation, the higher the flow (r = 0.43; P <.001) and the lower the increase in IP (r = -0.47; P <.001). A quadratic relation between flow and temperature was observed both for preheated fluid as when using the fluid heater (r(2) = 0.71 and r(2) = 0.88; P <.001). However, at low flow rates, a thermal decrease of over 3 degrees C was observed when the fluid heater was not used. CONCLUSIONS: The current study quantifies an expected relationship between the diameter of the irrigation channel and achievable flow rates. It also shows that a medical fluid heater is needed when strict control of temperature would be desired. PMID- 11781981 TI - The management of fetal ovarian cysts. AB - BACKGROUND/PURPOSE: Ovarian torsion causing the loss of an ovary represents the most common complication of fetal ovarian cysts and occurs more frequently before than after birth. Thus, treatment of fetal simple ovarian cysts should be performed antenatally; however, criteria for prenatal decompression still need to be evaluated. Previous experience of the authors showed that large simple cysts have a poor outcome, whereas preliminary attempts of their "in utero" aspiration were all successful and uneventful. The authors evaluated the outcome of fetal simple ovarian cysts after prenatal aspiration and considered criteria for this procedure. The outcome of cysts showing a prenatal ultrasound pattern of torsion also was studied. METHODS: This prospective study includes 73 ovarian cysts (48 simple, 25 showing torsion) diagnosed in 72 fetuses from June 1992 to June 1999, and followed up until spontaneous resolution or surgery. Prenatal aspiration was performed in the case of simple cysts >/=5 cm in diameter. The outcome of these cysts was compared with that of similar cysts not aspirated in the authors previous study (X(2). Cysts with an US pattern of torsion persisting at birth were operated on. The outcome of simple cysts less than 5 cm and cysts with a prenatal ultrasound appearance of torsion also was evaluated. RESULTS: Prenatal decompression was performed without any complications in 14 cases: 12 (86%; 95% CI: 0.68 to 1.00) regressed subsequently; 2 (14%; 95% CI: 0.00 to 0.32) showed torsion postnatally. This outcome is significantly better than that of similar cysts not aspirated in the authors' previous study(10) (P =.0002). Among the 34 simple cysts less than 5 cm, 26 (76%; 95% CI: 0.62 to 0.90) resolved spontaneously; 8 (24%; 95% CI: 0.10 to 0.38) had complications, 7 of which showing torsion (diameter at evidence of torsion, 4.4 cm [median]; range, 3.3 to 5.2 cm). Among the 34 cysts showing torsion (25 with initial US pattern of torsion + 9 subsequently complicated simple cysts), 24 (71%; 95% CI: 0.56 to 0.86) required oophorectomy; 9 (26%; 95% CI: 0.11 to 0.41) spontaneously disappeared at ultrasound, one of which required surgery for intestinal obstruction secondary to adhesion of a necrotic ovary; one patient (3%; 95% CI: 0.00 to 0.09) was lost to follow-up. CONCLUSIONS: Prenatal aspiration of ovarian cysts appears effective and safe: a "cutoff" of 4 cm should be investigated. Cysts with ultrasound pattern of torsion persisting postnatally require surgery; options for their management, when sonographically disappearing and asymptomatic, need to be investigated. PMID- 11781982 TI - Meconium dependence of bowel damage in gastroschisis. AB - BACKGROUND/PURPOSE: Increasing evidence of physiologic in utero defecation supports the hypothesis that bowel damage in gastroschisis may be meconium dependent. In this study, the author investigated the role of meconium on parameters of bowel damage in a fetal rat model of gastroschisis. METHODS: Pregnant rats underwent laparotomy at 18 1/2 days gestational age (GA). There were 4 experimental groups of 11 fetuses each; the G(M) group consisted of fetuses with isolated gastroschisis and was considered to have moderate meconium contamination of the amniotic fluid (MCAF); the G(L) group consisted of fetuses with gastroschisis and anal ligation, performed to prevent MCAF; the G(H) group consisted of fetuses with gastroschisis and colon perforation, performed to increase MCAF; and the Sham group consisted of sham operated controls. All fetuses were harvested by cesarean section at 21 1/2 days GA, and the fetal intestine was assessed for peel, intestinal length, intestinal weight per unit length, and histologic appearance. RESULTS: The authors achieved the following fetal survival rates: G(M) group, 91% (10 of 11); G(L) group, 78% (7 of 9, the ligation was not successful in 2 fetuses); G(H) group, 82% (9 of 11). Sham group, 100% (11 of 11). Intestinal length was decreased in fetuses with gastroschisis, and this reduction was related directly to the grade of MCAF (Sham, 18.4 +/- 0.6; G(L), 11.5 +/- 0.5; G(M), 10.2 +/- 0.6; G(H), 9.1 +/- 0.6 cm; P <.01). In contrast, intestinal weight per unit length increased in fetuses with gastroschisis, and this increase was related directly to the grade of MCAF (Sham, 7.8 +/- 0.5; G(L), 9.4 +/- 0.5; G(M), 11.3 +/- 0.5; G(H), 16.9 +/- 0.7 mg/cm; P <.01). In comparison with the G(M) group, the degree of peel coverage and bowel adherence were increased markedly in the G(H) group, whereas the fetuses of the G(L) group had neither peel nor bowel adherence. CONCLUSIONS: All bowel damage parameters were affected by MCAF supporting the hypothesis that bowel damage in gastroschisis is at least partially dependent on meconium exposure. Further research is required to clarify other factors that contribute to bowel damage and to identify risk factors that may allow prenatal identification of severely affected fetuses. PMID- 11781983 TI - Acute acalculous cholecystitis in children: Diagnosis and treatment. AB - PURPOSE: In this study, 12 patients with acute acalculous cholecystitis (AAC) who underwent diagnosis and treatment at the authors' clinic were discussed. METHODS: Nine of these patients were boys, and 3 were girls. The mean age was 7.8 years. Almost all had fever, abdominal pain, and tenderness. Other manifestations included vomiting (75%) and jaundice (41%). Results of laboratory tests showed leucocytosis (83%) and abnormal liver function (66%). Three patients (25%) had previous operations (2 perforated appendicitis and 1 osteomylitis), and 4 (33%) had a previous blunt abdominal trauma. Five patients (41%) had underlying infectious disease. Diagnosis was suspected clinically and confirmed by ultrasonography (USG). USG criteria for AAC consisted of gallbladder (GB) distension, GB wall thickness (>3.5 mm), nonshadowing echogenic materials or sludge, and pericholecystic fluid collections. All patients were treated initially nonoperatively with nasogastric suction, intravenous fluids and antibiotics. They were followed by daily USG examinations, clinical condition, physical examinations, and laboratory findings for determining the timing of operative intervention. RESULTS: GB distension was found in 50% of patients, a thickened GB wall in 100%, nonshadowing echogenic materials or sludge in 50%, and pericholecystic fluid in 41% at first USG examinations of patients. The combination of the least 2 USG criteria was noticed in all patients. Daily USG examinations also were helpful in confirming the diagnosis in our series. In contrast to the other 9 patients, daily USG examinations found a progressive increasing GB wall thickness and distension, or a persistent appearance of the nonshadowing echogenic materials or sludge and pericholecystic fluid in 3 (25%). Cholecystectomy was performed in these patients. In the other 9 patients (75%), daily USG examinations found a progressive improvement in the previous USG findings. They recovered fully and complete resolution of symptoms and signs related to AAC with nonoperative treatment resulted. CONCLUSIONS: USG is the most reliable method of early diagnosis of AAC. In addition, follow-up USG criteria are earlier and much more reliable in determining the most favorable time for operative intervention than those of clinical and laboratory criteria used conventionally in AAC patients who had underlying diseases. So, the authors suggest that initially nonoperative treatment of AAC is safe and effective in most cases. PMID- 11781984 TI - Individual inactivation of the sphincteric component of the gastroesophageal barrier causes reflux esophagitis in piglets. AB - BACKGROUND/PURPOSE: The lower esophageal sphincter and the diaphragmatic crural sling form the gastroesophageal barrier. This work shows that division of the sphincteric component alone suffices to induce reflux esophagitis in piglets. METHODS: Male piglets underwent either sham operation (n = 7) or extramucosal myotomy of the gastroesophageal junction (n = 8). Before and 1 week after the operation, pull-through manometry was performed under sedation. Pressures taken on the 4 quadrants at 20 1-mm intervals on both time endpoints were compared by pairwise Wilcoxon tests. The distal esophagus was studied histologically after 8 weeks. RESULTS: The pressure profiles did not change after sham operation. In contrast, they were significantly flattened in the distal half of the high pressure zone after myotomy reflecting disappearance of the sphincteric component of the barrier. Esophagitis was seen in all myotomized piglets but in none from the sham group. CONCLUSIONS: Lower esophageal sphincter myotomy alone with preservation of the crural sling induces reflux esophagitis in piglets. This animal, widely available and not too costly, is an excellent model for gastroesophageal research. PMID- 11781985 TI - The application of vascular technology to esophageal and airway strictures. AB - BACKGROUND/PURPOSE: Strictures of the esophagus and airway tract can be dilated if the strictures can be traversed and dilators passed. Unfortunately, using standard methods, not all strictures can be traversed. The authors set out to find a safe, expeditious, and reproducible way to traverse otherwise impassable strictures of the esophagus and airway. METHODS: Eight patients (n = 8), over a 2 year period, with strictures were entered prospectively into the study. One patient (n = 1) had a main stem bronchial stricture, and 7 patients (n = 7) had esophageal strictures from the following etiologies: esophageal atresia/tracheoesophageal fistula (EA/TEF) repair, Lye ingestion (n = 2), EA/TEF with gastroesophageal reflux, esophageal atresia without fistula, lye ingestion with colon interposition (n = 2), and iron pill inhalation lodged in left main bronchus. None of the strictures could be passed with conventional maneuvers or instrumentation including endoscopy, guide wires, Fogarty catheters, and filliform and followers. Results of barium studies showed no flow into the stomach. In the bronchial case, no lumen could be identified at bronchoscopy. RESULTS: Utilizing the "Vascular Surgery Glidewire/Berenstein Catheter System" under fluoroscopy and utilizing the "spinning top" dynamic maneuver intrinsic to this system, all of the strictures were traversed easily. The passage of the wire/catheter system thus allowed sequential dilation of the previously impassable strictures. The mean time to cross the strictures with the wire/catheter system was 1 minute, 10 seconds. (t = 70 seconds). All of the procedures were done in the operating room under general endotracheal anesthesia by the same 2 attending pediatric surgeons. CONCLUSIONS: The use of vascular surgical technology in difficult, otherwise impassable strictures of the esophagus and upper airway proved to be an extremely effective, easy-to-perform, and reproducible method of therapy. This procedure may obviate the need for resectional surgery in this setting. PMID- 11781986 TI - Diagnosing childhood tumors: A review of 147 cutting needle biopsies in 110 children. AB - BACKGROUND/PURPOSE: The aims of this study were to evaluate the diagnostic accuracy and safety of cutting needle biopsy for diagnosis in children with tumors suspected for malignancy. METHODS: Medical records and biopsy slides recorded from 1988 to 1999 were reviewed. One hundred ten patients had undergone a total of 147 cutting needle biopsies. The biopsy was performed under ultrasound guidance, using a 1.2-mm (18 gauge) Biopsy-cut biopsy needle. The diagnoses were benign tumors (n = 8), malignant tumors (n = 84), and nonneoplastic diseases (n = 18), with repeat biopsy performed in 24 patients. RESULTS: The diagnostic accuracy of cutting needle biopsies was 89% (131 of 147). The accuracy for pretreatment diagnosis was 88% (102 of 116), and for confirming or excluding a recurrence or metastasis 93% (26 of 28). The sensitivity of this method was 82% (86 of 105), and the positive predictive value 99% (86 of 87). Nondiagnostic cutting needle biopsy (n = 16) was not related to the age of the patient, experience of the radiologist, number of needle insertions, or site of puncture. No patient exhibited tumor growth along the needle tract. Complications occurred in 10 cases (7%) and pain in 20 (14%). CONCLUSION: Cutting needle biopsy is an accurate and safe procedure with a low learning threshold that is recommended for diagnosing malignancies in childhood. PMID- 11781987 TI - Feasibility of partial nephrectomy for Wilms' tumor in children with Beckwith Wiedemann syndrome who have been screened with abdominal ultrasonography. AB - BACKGROUND: Children with Beckwith-Wiedemann syndrome (BWS), a congenital syndrome associated with Wilms' tumor commonly are screened with abdominal sonography resulting in detection of tumor at a lower stage. Wilms' tumors have been traditionally treated with complete nephrectomy; however, smaller tumors are amenable to nephron-sparing surgery. Because Wilms' tumors may be metachronous and nonmalignant disease may compromise renal function in BWS, nephron-sparing approaches may be desirable as the first option. METHODS: Seven patients with BWS and Wilms' tumor underwent nephrectomy. The preoperative computed tomography (CT) or ultrasound scan were evaluated by a pediatric surgeon to assess whether partial nephrectomy would have been feasible. The determining criteria included tumor involving one third or less of the kidney and no involvement of either hilar or vascular structures. RESULTS: Seven patients underwent complete nephrectomies. The remaining patient, who had undergone a left nephrectomy before the initiation of screening had salvage chemotherapy after biopsy results showed right kidney involvement with Wilms' tumor. CONCLUSIONS: Nephron-sparing surgery is reasonable to consider in children with Beckwith-Wiedemann syndrome who are screened at intervals of 4 months or less. The relative benefits of partial nephrectomy for children with Wilms' tumor-predisposing conditions only can be assessed in the setting of a cooperative clinical trial. PMID- 11781989 TI - Proctocolectomy and J-pouch ileo-anal anastomosis in children. AB - BACKGROUND/PURPOSE: The choice of ileo-anal reconstruction method in children undergoing proctocolectomy remains controversial. Although in adults ileo-anal pouch reconstruction has gained overall acceptance, many paediatric surgeons still advocate straight ileo-anal pull-through. The aim of this study was to assess the outcome and long-term functional results in children who have undergone proctocolectomy and ileo-anal anastomosis (IAA) with a J-pouch. METHODS: Medical records of 40 consecutive children who had proctocolectomy and J pouch IAA between 1991 and 1999 were reviewed for early and late complications, fecal frequency, day- and night-time continence, and pouchitis. The indication for surgery was ulcerative colitis (UC) in 29 (median age at operation, 13 years; range, 9 to 16), Hirschsprung's disease (HD) in 10 (median age at operation, 1.5 years; range, 1 month to 5 years), and familial adenomatous polyposis (FAP) in 1 (age at operation, 6 years). Six of the HD patients had primary pull-through for total colonic aganglionosis and 4 a redo operation for failed primary reconstruction of long segment aganglionosis. RESULTS: There were no fatalities. Early complications (wound infection, early bowel obstruction, prolonged fever) occurred in 12 of 29 (41%) and late complications (bowel obstruction 9, pouch fistula 2) in 11 of 29 (38%) of the UC patients. Overall, 16 of 29 (53%) of the UC patients had complications. All patients with early complications were on systemic steroids at the time of the operation. Pouchitis occurred in 30% of the patients. None of the pouches had to be removed. At last follow-up all patients were continent during the day, 2 patients used protective pads during the night because of occasional staining. The median bowel frequency per 24 hours was 4 (range, 2 to 7); only 2 patients (7%) had to empty their bowel during the night. One (10%) of the HD patients had wound infection, and 3 had episodes of postoperative enterocolitis. Pouchitis-type symptoms have not occurred in HD patients. The median bowel frequency for 24 hours was 3 (range, 2 to 5). None of the HD patients needs to evacuate during the night. The 4 HD patients who are older than 3 years of age are continent. CONCLUSIONS: J-pouch IAA is a feasible method of reconstruction in children requiring proctocolectomy. Major complication are common but occur mainly in immunosuppressed patients suffering from UC. Despite high incidence of complications, long-term functional results in terms of continence and bowel frequency are excellent and ensure good quality of life in the great majority of patients. PMID- 11781988 TI - Excellent long-term outcome for survivors of apple peel atresia. AB - BACKGROUND: Apple peel atresia is the rarest type of small bowel atresia. Because of its rare occurrence and high mortality rate, little is known about the long term outcome of these children. METHODS: The patient charts, operative reports, and office notes of 15 children with apple peel atresia from 6 pediatric surgical centers in the Netherlands were reviewed. Long-term follow-up was assessed through review of office notes and through questionnaires. RESULTS: The median age at the time of operation was 1.5 days. Postoperatively, 53% suffered from cholestasis, and 40% were septic. Three patients died (20%). At follow-up at a median age of 24 months, 1 child showed growth retardation and 2 children suffered from short bowel syndrome. At the time of the questionnaire, all children showed normal growth and development. CONCLUSIONS: Even though children with apple peel atresia often suffer serious morbidity like short bowel syndrome and sepsis during the postoperative course, late morbidity turned out to be low. If the patients survive the operative and direct postoperative period, and survive the morbidity associated with malnutrition and the long-term use of total parenteral nutrition, they have a good chance of having normal bowel function with normal growth and development. PMID- 11781990 TI - Do prognostic factors exist for total colonic aganglionosis with ileal involvement? AB - BACKGROUND/PURPOSE: Total colonic aganglionosis with ileal involvement is estimated at 1 case in 50,000 living births. This pathology has a very variable prognosis, and patients often need long-term parenteral nutrition. The aim of this study is to define prognostic factors for this disease. METHODS: This is a retrospective study from 1980 to 1999, based on 26 cases of total colonic aganglionosis with ileal involvement. The authors analyzed birth term, sex, birth weight, ileal involvement in centimeters, delay to correct level enterostomy, the total parenteral nutrition duration, and the need for constant rate nutritional assistance. The authors studied the following items: Weight, height, complications, clinical state, and nutritional issues. The statistic test is: LOG RANK (analysis of censored data and comparison of survival diagram). RESULTS: The only prognostic factor is the length of ileal involvement. All the children with ileal involvement less than 50 cm, except for 2, did not need long-term nutritional assistance; for those with ileal resection over 50 cm, long-term nutritional assistance was needed. Total colonic aganglionosis is a very serious illness (2 children had a small bowel transplantation, and 2 are waiting for one). The prognosis is even worse when associated with a polymalformation syndrome (50% of the children died). CONCLUSION: The major prognostic factor is the length of small bowel not involved in the total colonic aganglionosis. PMID- 11781991 TI - Surgical management of chronic unremitting constipation and fecal incontinence associated with megarectum: A preliminary report. AB - BACKGROUND/PURPOSE: Functional constipation with associated fecal incontinence responds poorly to medical management once megarectum has developed. The authors describe resecting the dilated rectum and inserting a cecostomy button for antegrade enemas in this difficult condition. METHODS: Four children, ages 9 to 15 years, with a history of unremitting constipation and fecal incontinence were referred for evaluation after not responding to medical management. All patients had exhibited normal lumbosacral magnetic resonance images (MRI) and open rectal biopsies; however, all 4 patients had a megarectum on contrast enema. In addition, anorectal manometry was consistent with functional fecal retention. The dilated rectum was resected by anastamosing the nondilated sigmoid colon to the distal rectum, and a standard gastrostomy button was inserted into the cecum for antegrade enemas. Mean follow-up was 35 months (range, 8 to 60 months). RESULTS: Constipation and incontinence resolved within 6 months in all patients, and all children remained continent without the aid of cathartic agents. There were no postoperative episodes of fecal impaction. The only complication was antibiotic associated diarrhea in 1 patient. Cecostomy buttons were removed at 1 year postplacement in all 4 patients with continued success. Three patients underwent repeat anorectal manometry; all 3 had normal rectal sensory threshold volumes and anorectal inhibitory reflexes. Barium studies also were obtained in the 3 patients without evidence of recurrent rectal dilation. CONCLUSIONS: Refractory constipation and incontinence associated with megarectum may be amenable to surgical intervention in selected patients. The authors' limited experience suggests that proctectomy and button cecostomy is an effective treatment option that improves the quality of life in these patients. Furthermore, proctectomy alone may be curative. PMID- 11781992 TI - Evaluation of the location of the anus by a modified technique in the neonate. AB - PURPOSE: The aim of the current study was to bring to notice the anterior displacement of the anus and to recommend the measurement of anal position index in the neonate by a modified method. METHODS: Sixty newborns (34 girls and 26 boys) were taken into study, and the anal position index (API), which is the ratio of anus-fourchette (scrotum) distance to coccyx fourchette (scrotum) distance, was measured. To obtain the measurement, a transparent adhesive tape was placed along the midline on the long axis, covering the anus. The upper and lower tips and the center of the anal circle was marked and measured using a caliber. RESULTS: API was found as 0.46 (SD +/- 0.08) and 0.53 (SD +/- 0.05) in female and male neonates, respectively. Because an index of 0.34 in girls and 0.46 in boys are considered abnormal, the 3 female babies in the study group with API indices of 0.18, 0.28, and 0.33 were subjected to further examination. The abnormality was seen not to be rare in the Aegean region. CONCLUSIONS: An abnormal index alone cannot be the sole cause of constipation mentioned in the literature and therefore not an indication for operation. Anal position index in the neonates could be measured more accurately by the current modified method. If an anterior location of the anus is found early in infancy the baby should undergo follow-up accordingly. PMID- 11781993 TI - The presentation and management of juvenile-onset chronic inflammatory bowel disease in Northeastern Scotland. AB - PURPOSE: This study reviews the presentation and management of juvenile onset chronic inflammatory bowel disease and identifies changes in incidence of the disease over a 20-year period. METHODS: This was a retrospective study of all patients aged 16 and under with chronic inflammatory bowel disease diagnosed in 1 health region between 1980 and 1999. The patients were identified from computer records and the following variables studied: age, sex, mode of presentation, medical and surgical management, and length of follow-up. RESULTS: One hundred seven patients were identified: 77 with Crohn's disease and 30 with ulcerative colitis. The incidence of ulcerative colitis and Crohn's disease has risen from 0.7 in 100,000 and 2.2 in 100,000, respectively, in the years 1980 through 1989 to 1.5 in 100,000 and 4.4 in 100,000 in the period 1990 through 1999. The median age at presentation was 10.1 years for ulcerative colitis and 10.8 years for Crohn's disease. The majority of disease was diagnosed within 1 year of the onset of symptoms, which were principally abdominal pain, diarrhea, and rectal bleeding. The average length of follow-up was 6.9 years. Analysis of the surgical management of Crohn's patients has shown a low rate of surgical intervention. CONCLUSIONS: This study has shown an increasing incidence of chronic inflammatory bowel disease in the Grampian region of Scotland coupled with a low rate of surgical intervention in Crohn's disease. These findings could be the result of early referral and diagnosis, with the disease being documented earlier in its course or more aggressive preemptive medical therapy. PMID- 11781994 TI - Release of toxic metals from button batteries retained in the stomach: An in vitro study. AB - BACKGROUND: Ingestion of button batteries by children is a rapidly growing problem, and opinions differ on how button batteries distal to the gastroesophageal junction should be managed. The authors therefore performed an experimental study to determine the cumulative load of various toxic elements released from retained button cells in simulated gastric juice. METHODS: Eight different groups of button cells were immersed in simulated gastric juice. Analyzed elements included Al, Ba, Cd, Cr, Cu, Fe, Hg, Li, Mg, Mn, Ni, Pb, Sb, Sn, Sr, Te, TI, V, W; and Zn. Inductively coupled plasma mass spectrometry (ICP MS) was used to evaluate the residual amounts of elements after 4, 24, 72, and 120 hours. RESULTS: At 4 hours, leakage was seen with almost all batteries, with the levels increasing in a time-dependent manner. The highest detected levels at 4 hours were 1.20 microgram for Cd, 280.51 ng for Hg, and 2.63 microgram for Pb. Dissolution, holes, and defragmentation were seen within 24 to 72 hours. Battery weight loss varied between 22 and 104 mg over the course of the study. CONCLUSIONS: Toxic elements contained in button cells are released quickly in gastric juice. This finding might change the current policy of watchful waiting or conservative management of batteries lodged in the stomach. PMID- 11781995 TI - The prognostic importance of trauma scoring systems for morbidity in children with penetrating abdominal wounds: 17 years of experience. AB - BACKGROUND/PURPOSE: Risk factors that may independently predict morbidity in children with penetrating abdominal wounds (PAW) have not been elucidated fully. The aim of this study was to identify not only correlated risk factors for morbidity in children with PAW, but also to evaluate the independent predictive value of 3 different trauma scoring systems: the Injury Severity Score (ISS), the Penetrating Abdominal Trauma Index (PATI), and the Pediatric Trauma Score (PTS). METHODS: Between January 1983 and November 2000, 119 children (99 boys, 20 girls) presenting with PAW were reevaluated by an analysis of the relationship between overall morbidity and potential risk factors. RESULTS: Wounds were caused by firearm trauma in 85 children and stabbing in 34. Univariate analysis found that age greater than 10 years, trauma mechanism, number of intraabdominal organs injured (NOI) greater than 2, presence of penetrating injury, and ISS and PATI score were associated with greater than 3-fold increased incidence of morbidity (P <.05). The relative risk of a postoperative septic complication was higher than 2 for the following risk factors: age greater than 10 years, shotgun injury, number of organs injured greater than 2, presence of colon injury, ISS greater than 15, and PATI score greater than 15. Multivariate analysis showed that only ISS (P =.02), and PATI score (P =.03) were independently significant in predicting morbidity. CONCLUSION: ISS and PATI score were the most important indicators found to be independently associated with morbidity. PMID- 11781996 TI - Genital and perineal burns in children: 10 years of experience at a major burn center. AB - PURPOSE: The aim of this report is to review a decade of experience in the management of perineal and genital burns at a major burn center. METHODS: Seventy eight children who sustained perineal or genital burns admitted to the Shriners Hospitals for Children in Galveston are discussed. RESULTS: Genital and perineal burns occurred in the context of major burns and were rarely isolated. A total of 64.1% were caused by hot liquids (scalds), 29.5% were flame burns, 3.8% contact burns, and 2.6% electrical burns. A total of 61% of the burns could be treated conservatively with loose debridement, topical, and parenteral antibiotics with satisfactory outcomes. Foley catheterization did not increase the morbidity in these patients except in children less than 1 year of age. Testicular involvement was associated with the most severe burns. Child abuse was found in 46% and 48% of boys and girls, respectively, younger than 2 years that had sustained scald burns to the perineum and, or genitals. CONCLUSIONS: Most perineal and genital burns in children can be treated successfully with a conservative approach. Child abuse should be vigorously investigated. PMID- 11781997 TI - Staged proximal hypospadias repair: Modified thiersch duplay with midline incision in urethral plate followed by Mathieu urethroplasty. AB - PURPOSE: Functional results, complications, cosmesis, operating time, and hospital stay were analyzed after staged urethroplasty for proximal hypospadias. METHODS: Seventeen consecutive boys, mean age 17.7 +/- 1.6 months underwent a staged urethroplasty in the past 5 years. Urethral plate was tubularized and proximal hypospadias converted to distal. Hooded dorsal prepuce was buttonholed and transposed ventrally to cover the neo-urethra. Subsequently, a parameatal based flip flap urethroplasty completed the urethral reconstruction at mean age of 26.7 +/- 4.1 months. RESULTS: Mean follow-up time was 2.8 +/- 1.7 years. Eighty-eight percent of boys who are now toilet trained and standing to void have a good caliber straight single stream of urine in a forward direction. Urethrocutaneous fistula was seen in 1 child (6%), and a simple fistulectomy with double layered closure was successful at first attempt of fistula closure. Cosmetic appearance of a natural vertical slit glanular meatus situated at normal position on the glans was achieved in all patients. Total mean operating time was 193.5 +/- 42.9 minutes and total mean duration of hospital stay was 3.4 +/- 0.6 days. CONCLUSION: Staged urethroplasty for proximal hypospadias results in a normal penis with good function, minimal complications, and excellent cosmesis. PMID- 11781999 TI - An asymmetric ballooning of the neck: Jugular vein aneurysm. AB - The differential diagnosis and treatment of a 2-year-old boy with a left-sided cystic neck bulge enlarged in size while straining, coughing, and crying is presented. Contemporary diagnostic tools were of little value, whereas its location, variability in size, and consistency at physical examination played a major impact. Simple excision of the venous aneurysm was sufficient in its treatment. PMID- 11781998 TI - Chromobacterium violaceum infection: A rare but frequently fatal disease. AB - The authors report a rare case of Chromobacterium violaceum infection in a 2 month-old child. She presented with an apparently localized abscess, which appeared to respond well to therapy. However, the infection recurred later with a fulminant course. The organism frequently is dismissed as a contaminant or not identified properly, and the fatality rates are high. A high degree of awareness about this infection needs to be created, especially among pediatricians and pediatric surgeons, because children appear to be infected more commonly than adults, and aggressive therapy is needed to save these patients. PMID- 11782000 TI - Giant ileal duplication with extensive gastric heterotopia. AB - A rare case of ileal duplication in a 6-year-old boy is presented. The duplicated area is just like an additional ectopic stomach both in radiologic and pathologic examination. The patient was operated on because of intestinal obstruction. PMID- 11782001 TI - A new variant of esophageal atresia associated with esophageal heterotopic pancreas. AB - An infant with esophageal atresia (EA) and absence of gas on abdominal radiographs was found to have an obliterated distal tracheoesophageal fistula (TEF). Preoperative bronchoscopy and surgical exploration found that the reason for gasless abdomen was the atresia of the distal portion of lower esophagus, which also contained heterotopic pancreatic tissue. The type of trachea/esophageal anomaly found in this patient, with the association of esophageal heterotopic pancreas (EHP), has not yet been reported in the literature. PMID- 11782002 TI - A rare cause of gastric outlet obstruction in the newborn: Pyloric ectopic pancreas. AB - This report describes a case of symptomatic pyloric ectopic pancreas simulating infantile hypertrophic pyloric stenosis (IHPS) in an 1-month-old boy. There are few cases reported in the English-language literature with the same clinical presentation during the neonatal period. Rarely is the entity symptomatic, and it should be kept in mind in differential diagnosis of nonbilious vomiting, especially in neonates. The ectopic pancreas should be removed because of the late complications when found incidentally. PMID- 11782003 TI - Epidermoid cyst of the testis in an adolescent: Case report and review of the evolution of the surgical management. AB - Epidermoid cyst, a tumorlike lesion, is a rare benign testicular tumor with typical, distinctive ultrasonographic appearance. When the preoperative features are highly suggestive of epidermoid cyst, testicular sparing surgery after strict oncologic guidelines is warranted. The authors report a case of a preoperatively suspected epidermoid cyst in an adolescent and review the literature concerning the changing paradigm of management. PMID- 11782004 TI - Myofibroblastic tumors involving bilateral adrenal glands and skin in a patient with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) is a heterogeneous form of primary immune deficiency characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome have an increased incidence of autoimmune diseases and malignancy. A patient with CVID in whom myofibroblastic tumors affecting both adrenal glands and skin is presented. PMID- 11782005 TI - Wilms' tumor of the ovary: A case report. AB - The occurrence of true extrarenal Wilms' tumor is extremely rare. The most frequently noted extrarenal sites are the retroperitoneal and inguinal regions. In the female genital tract, the occurrence of Wilms' tumor has been documented in the uterus, endocervix, and ovary in isolated case reports. In this article the authors describe a case of ovarian Wilms' tumor in a 3.5-year-old girl. Her abdominal ultrasound scan and computed tomography scan showed a solid mass with cystic components on the left lower quadrant. Total excision was performed with left salpingo-oophorectomy. There was no other mass and also no evidence of metastasis. To the best of the authors' knowledge, this patient is the first reported case of primary ovarian Wilms' tumor arising in childhood. PMID- 11782006 TI - Transient renal insufficiency by bilateral renal cysts and posterior urethral valves. AB - Renal insufficiency developed in a newborn with huge bilateral renal cysts and posterior urethral valves. Definitive therapy consisted of laser coagulation of the valves and transient percutaneous drainage of the cysts. PMID- 11782007 TI - Two cases of anal fistula in girls evaluated for sexual abuse. AB - Anal fistulae are seen infrequently in the pediatric population. They are most commonly encountered in otherwise healthy boys less than 1 year of age. In the scant literature regarding pediatric anal fistulae, the majority of studies and case reports involve children less than 1 year of age. Within a 2-year period 2 school age girls presented to the authors' clinic with anal fistulae without history of a perianal abscess and without predisposing factors. Both of these children had a history of sexual abuse. We believe that in an otherwise healthy school age girl the appearance of an anal fistula should raise concern for the possibility of sexual abuse. PMID- 11782008 TI - Testicular artery sparing laparoscopic varicoceletomy (LV) in adolescents. PMID- 11782009 TI - An elegant method of reducing surgical trauma when dealing with a large simple neonatal ovarian cyst. PMID- 11782010 TI - Traumatic tear of aorta, trachea, and esophagus in a 7-year-old survivor. AB - In August 1996, a 7-year-old boy was crushed from behind into the steering wheel of a go-cart, suffering a tear of his right innominate artery into the aortic arch, a 2-inch tear of the posterior trachea into left main bronchus, and 2 4 inch tears in the esophagus. These were all repaired on cardiopulmonary bypass through a sternotomy; a Gor-tex (W. L. Gore and Associates, Flagstaff, AZ) graft was required for the arterial repair. His recovery was complicated by a midesophageal stricture and a nearby fistula to the left main bronchus, which caused frequent lung infections and 12 hospital admissions over 2(1/2) years. During this time he had his stricture dilated 5 times and resected twice, his fistula surgically closed twice and glued 4 times, and an antireflux procedure, pyloroplasty, and gastrostomy for his persistent gastroesophageal reflux. He also had 2 esophageal stents placed; the first (titanium) lasted 4 months and the second (SILASTIC(R) [Dow Corning, Midland, MI]) 1 year later lasted 9 months, solving both the stricture and fistula problems and spontaneously passing through and out of his gastrointestinal tract. Throughout this recovery time, his nutrition was maintained mostly by gastrostomy feeding, supplemented by total parenteral nutrition and oral feeding when able. After 2(1/2) years of treatment, all has returned to normal, and he has remained well for the last 2(1/2) years (April 2001). He still is on Omeprazole. PMID- 11782011 TI - Intestinal atresia presenting as bilateral scrotal pneumatocele: A case report. AB - The authors report on a newborn baby with congenital hydrocele in whom pneumoscrotum developed. Air and meconium were found over the hernia sac, owing to ileal atresia with perforation. Gas in the scrotum usually is inside herniated bowel, but it can be the first sign of pneumoperitoneum. PMID- 11782012 TI - Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor-specific antigens. AB - The Human MHC Project aims at comprehensive cataloging of peptides presented within the context of different human leukocyte antigens (HLA) expressed by cells of various tissue origins, both in health and in disease. Of major interest are peptides presented on cancer cells, which include peptides derived from tumor antigens that are of interest for immunotherapy. Here, HLA-restricted tumor specific antigens were identified by transfecting human breast, ovarian and prostate tumor cell lines with truncated genes of HLA-A2 and HLA-B7. Soluble HLA secreted by these cell lines were purified by affinity chromatography and analyzed by nano-capillary electrospray ionization-tandem mass spectrometry. Typically, a large peptide pool was recovered and sequenced including peptides derived from MAGE-B2 and mucin and other new tumor-derived antigens that may serve as potential candidates for immunotherapy. PMID- 11782013 TI - Requirement of Fas expression in B cells for tolerance induction. AB - Fas is a death receptor that belongs to the tumor necrosis factor receptor family and is expressed in various cell types, in particular, in lymphoid cells. A loss of-function mutation in the Fas gene (lpr mutation) causes lymphadenopathy and splenomegaly, and accelerates autoimmune diseases in some strains of mice such as MRL. In this report, Fas cDNA driven by murine lck distal promoter was used to establish transgenic MRL-lpr mouse lines. The transgenic mice expressed functional Fas in mature T cells and B cells. The lymphadenopathy and splenomegaly caused by accumulation of abnormal T cells in the lpr mice were rescued in the transgenic mice. The number of B cells in the periphery as well as the serum IgG level were significantly reduced, and the autoimmune symptoms and mortality were ameliorated. These results indicate that both mature B cells and T cells must undergo Fas-mediated apoptosis to prevent the development of autoimmune diseases. PMID- 11782014 TI - Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. AB - To reach the site of antigen deposition at epithelial surfaces, dendritic cells (DC) have to traverse the endothelial barrier, progress through the tissue (i.e., dermis) and cross the dermo-epithelial junction (basal membrane). In the present study, we demonstrate that (1) circulating blood DC and monocytes express high levels of CCR2 and primarily respond to monocyte chemotactic protein (MCP) and not to macrophage inflammatory protein (MIP)-3alpha/CCL20; (2) while the CD34(+) hematopoietic progenitor cells (HPC)-derived CD1a(+) precursors committed to Langerhans cell differentiation primarily respond to MIP-3alpha/CCL20, the HPC derived CD14(+) precursors respond to both MCP and MIP-3alpha/CCL20; (3) in concordance with the sequential expression of CCR2 and CCR6, the HPC-derived CD14(+) precursors initially acquire the ability to migrate in response to MCP 4/CCL13 and subsequently in response to MIP-3alpha/CCL20; and (4) in vivo, in inflamed epithelium, MCP-4/CCL13 and MIP-3alpha/CCL20 form complementary gradients, with MCP-4/CCL13 expressed in basal epithelial cells at the contact of blood vessels, while MIP-3alpha/CCL20 expression is restricted to epithelial cells bordering the external milieu. These observations suggest that the recruitment of DC to the site of infection is controlled by the sequential action of different chemokines: (i) CCR2(+) circulating DC or DC precursors are mobilized into the tissue via the expression of MCP by cells lining blood vessels, and (ii) these cells traffic from the tissue to the site of pathogen invasion via the production of MIP-3alpha/CL20 by epithelial cells and the up regulation of CCR6 in response to the tissue environment. PMID- 11782015 TI - The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross. AB - The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjogren's syndrome. In humans, Sjogren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis. In the present study the genetic control of sialadenitis in mice was compared to that of arthritis. We have previously reported a NOD locus, identified in an F2 cross with the H2(q) congenic NOD (NOD.Q) and C57BL/10.Q (B10.Q) strains, that promoted susceptibility to collagen induced arthritis. The sialadenitis in NOD.Q showed a similar histological phenotype as in NOD, whereas no submandibular gland infiltration was found in B10.Q. The development of sialadenitis was independent of immunization with type II collagen and established arthritis. To identify the genetic control of sialadenitis, a gene segregation experiment was performed on an (NOD.QxB10.Q)F2 cross and genetic mapping of 353 F2 mice revealed one significant locus associated with sialadenitis on chromosome 4, LOD score 4.7. The NOD.Q allele mediated susceptibility under a recessive inheritance pattern. The genetic control of sialadenitis seemed to be unique in comparison to diabetes and arthritis, as no loci associated with these diseases have been identified at the same location. PMID- 11782016 TI - The S128R polymorphism of E-selectin mediates neuraminidase-resistant tethering of myeloid cells under shear flow. AB - E-selectin mediates the rolling of circulating leukocytes on vascular endothelial cells. A polymorphism, in which serine is substituted for arginine at position 128 (S128R) in the EGF domain, has been associated with both early-onset atherosclerosis and SLE. We investigated whether the substitution alters the ligand-binding properties of E-selectin under shear flow by studying the capacity of Chinese hamster ovary cell transfectants expressing wild type (WT) or S128R E selectin to support interactions of neutrophils, K562 cells or HL60 cells. We initially chose to study non-fucosylated K562 cells. No interactions were observed on WT E-selectin, whereas S128R supported a transient tethering interaction of K562 cells, which was resistant to digestion with either neuraminidase or O-sialoglycoprotein endopeptidase, and, in turn, could result in firm adhesion in the presence of a beta2-integrin. HL60 cells exhibited increased rolling on S128R E-selectin. Although neuraminidase treatment inhibited all HL60 interactions with WT E-selectin, it unmasked transient tethers on S128R. We further observed that S128R recruited significantly more neutrophils than WT E selectin, without affecting neutrophil rolling velocity. This polymorphism may therefore amplify leukocyte-endothelial cell interactions and may be a factor linking the S128R polymorphism to vascular disease. PMID- 11782017 TI - Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis. AB - IL-12(p70), a heterodimer composed of two subunits (p35 and p40), is a key cytokine for Th1 mediated inflammatory responses. We dissected the role of IL-12 in the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis by studying mice deficient in IL-12p40, IL-12p35, or IL-12Rbeta1. TNBS-treated IL 12Rbeta1(-/-) and IL-12p35(-/-) mice developed only a mild disease associated with low level IL-18 expression in IL-12p35(-/-) mice. In contrast, IL-12p40(-/-) mice developed more severe colitis than wild-type mice associated with high level colonic IL-18 expression. Administration of IL-12p40 neutralizing mononuclear antibody dramatically increased pathology in IL-12p35(-/-) mice similar to disease scored in IL-12p40(-/-) mice. Numbers of IFN-gamma-producing cells infiltrating the lamina propria were comparably augmented in the different groups of IL-12-mutant and wild-type mice. These results demonstrate that IL-12p40, in contrast to IL-12p70, inhibits TNBS-induced colitis and IL-18 expression independent of IFN-gamma. PMID- 11782018 TI - Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy. AB - More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy. PMID- 11782019 TI - Peptide-pulsed splenic dendritic cells prime long-lasting CD8(+) T cell memory in the absence of cross-priming by host APC. AB - Immunization with cells expressing endogenous antigens can stimulate long-lived CD8(+) T cell memory. In many cases, the response is also stimulated by host antigen-presenting cells (APC) that have processed antigen from internalized apoptotic cells or cell fragments. This study investigated whether immunization with peptide-pulsed dendritic cells (DC) could prime long-lasting, peptide specific CD8(+) T cell immunity in the absence of cross-priming by host APC. C57BL / 6 female mice immunized with syngeneic male splenic DC pulsed with the H 2K(b)-restricted ovalbumin peptide OVA(257 - 264) made memory CD8(+) CD44(high) T cell responses to OVA(257 - 264) and the male antigen HY more than 1 year after immunization. Establishment and maintenance of peptide-specific CD8(+) T cell memory did not require antibody or B cells. Immunization of H-2(bxd) mice with OVA(257 - 264)-pulsed minor-incompatible H-2(b) or H-2(d) DC demonstrated that CD8(+) T cells were primed exclusively by the injected cells, and not by peptide transferred to host APC, even though there was very effective cross-priming for CD8(+) T cell responses to the minor antigens expressed by the DC. Thus peptide pulsed DC can prime long-lasting CD8(+) memory responses without any requirement for cross-priming by other APC. PMID- 11782020 TI - GL7 defines the cycling stage of pre-B cells in murine bone marrow. AB - We have identified a novel subset of early B lineage cells in the mouse bone marrow (BM) by GL7 expression on cell surface. GL7(+)B220(low) BM cells have a large cell size and are CD43(-to low), CD95(-), Sca-1(-), I-A(low), IgM(-) and IgD(-), suggesting that they are large pre-B cells. These BM cells express lambda5 and VpreB but not terminal deoxytransferase (TdT) and Bcl-2, and approximately 50 % of them are in cell cycle. This fraction was not detected in BM cells of Rag-1-deficient and Scid mice, supporting that GL7(+)B220(low) BM cells belong to fraction C' and D according to Hardy's criteria or to an early large pre-B-II fraction according to Melchers-Rolink's criteria. Furthermore, GL7(+)B220(low) BM cells can differentiate into IgM(+) immature B cells in co culture with stromal cells. These results suggest that B lymphocytes pass through the GL7(+) pre-B cell stage during differentiation in the BM. Thus, GL7 is the critical marker to define the proliferation stage of large pre-B cells. PMID- 11782021 TI - Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin. AB - Ankylosing spondylitis (AS) is highly associated with HLA-B27. We have previously shown that peripheral blood lymphocytes from AS patients respond to stimulation with a peptide from the sequence of HLA-B27. Here we report on molecular mimicry of peptides from HLA-B27 and cytokeratin, the latter being specifically expressed in synovial membranes and eyes, the main targets of the autoaggressive immune response in AS patients. Immunization of rats with these peptides induced an inflammatory response in joints, spine and eyes, resembling the symptoms in AS. Furthermore, both HLA-B27- and cytokeratin-derived peptides, are effective oral tolerogens: feeding these peptides ameliorated arthritis and uveitis induced with the cytokeratin peptide. Our model might elucidate the role of peptides from the sequence of HLA-B27 as an antigen of the immune response in AS, introducing a new aspect of antigenic mimicry between HLA-B27 and tissue-specific antigens. We propose this as a mechanism directing a systemic autoimmune response to specific target organs by antigenic mimicry of T cell epitopes. PMID- 11782024 TI - Bruno de Finetti: the mathematician, the statistician, the economist, the forerunner. AB - Bruno de Finetti is possibly the best known Italian applied mathematician of the 20th century, but was he really just a mathematician? Looking at his papers it is always possible to find original and pioneering contributions to the various fields he was interested in, where he always put his mathematical "formamentis" and skills at the service of the applications, often extending standard theories and models in order to achieve more general results. Many contributions are also devoted to educational issues, in mathematics in general and in probability and statistics in particular.He really thought that mathematics and, in particular, those topics related to uncertainty, should enter in everyday life as a useful support to everyone's decision making. He always imagined and lived mathematics as a basic tool both for better understanding and describing complex phenomena and for helping decision makers in assuming coherent and feasible actions. His many important contributions to the theory of probability and to mathematical statistics are well known all over the world, thus, in the following, minor, but still pioneering, aspects of his work, related both to theory and to applications of mathematical tools, and to his work in the field of education and training of teachers, are presented. PMID- 11782025 TI - Comparison of smoothing techniques for CD4 data in a Markov model with states defined by CD4: an example on the estimation of the HIV incubation time distribution. AB - Multi-state models defined in terms of CD4 counts are useful for modelling HIV disease progression. A Markov model with six progressive CD4-based states and an absorbing state (AIDS) was used to estimate the cumulative probability of progressing to AIDS in 158 HIV-1 infected haemophiliacs with known seroconversion (SC) dates. A problem arising in such analysis is how to define CD4-based states, since this marker is subject to measurement error and short timescale variability. Four approaches were used: no smoothing, ad hoc smoothing (to move to a later/previous state two consecutive measurements to later/previous states are needed), kernel smoothing and random effects (RE) models. The estimates were compared with the Kaplan-Meier estimate based solely on data concerning time to AIDS. There was an apparent lack of agreement between the Kaplan-Meier and the "no smoothing" estimate. With the exception of the "no smoothing" method, "ad hoc", kernel and RE estimates fell within the range of the 95 per cent CIs of the Kaplan-Meier curve. Simulations demonstrated that the use of raw CD4 counts provides overestimated transition intensities. Compared to the kernel method, ad hoc is easier to implement and overcomes the problem of the choice of bandwidth. The RE approach leads to simple models, since it usually results in very few transitions to previous states, and can handle individuals with sparse data by smoothing their predictions towards the population mean. Ad hoc was the method that performed better, in terms of bias, than the other smoothing approaches. PMID- 11782026 TI - Modelling cause-specific hazards with radial basis function artificial neural networks: application to 2233 breast cancer patients. AB - The clinical course of a disease is often characterized by the possible occurrence of different types of events acting in a competing way. From a statistical point of view this translates into the need of modelling the dependence of cause-specific hazards as a function of covariates. Generalized linear models with Poisson error have previously been adopted for the analysis of competing risks as a function of discrete covariates. In the present paper an artificial neural network extension for the flexible joint estimation of cause specific hazards depending on both discrete and continuous covariates is proposed. This approach is based on radial basis function networks which have the advantage of allowing parameter estimation by the adoption of standard software for generalized linear models. We have applied this method to data from 2233 breast cancer patients to investigate the effects of age, tumour size, number of metastatic axillary nodes, histology and tumour site on cause-specific hazards for intra-breast tumour recurrences and distant metastases. The adoption of a radial basis function network made it possible to highlight effects that were not considered by previous analyses of the same data. PMID- 11782027 TI - Estimation of bivariate measurements having different change points, with application to cognitive ageing. AB - Longitudinal studies of ageing make repeated observations of multiple measurements on each subject. Change point models are often used to model longitudinal data. We demonstrate the use of Bayesian and profile likelihood methods to simultaneously estimate different change points in the longitudinal course of two different measurements of cognitive function in subjects in the Bronx Aging Study who developed Alzheimer's disease (AD). Analyses show that accelerated memory decline, as measured by Buschke Selective Reminding, begins between seven and eight years before diagnosis of AD, while decline in performance on speeded tasks as measured by WAIS Performance IQ begins slightly more than two years before diagnosis, significantly after the decline in memory. PMID- 11782028 TI - Impact of missing data due to drop-outs on estimators for rates of change in longitudinal studies: a simulation study. AB - Many cohort studies and clinical trials are designed to compare rates of change over time in one or more disease markers in several groups. One major problem in such longitudinal studies is missing data due to patient drop-out. The bias and efficiency of six different methods to estimate rates of changes in longitudinal studies with incomplete observations were compared: generalized estimating equation estimates (GEE) proposed by Liang and Zeger (1986); unweighted average of ordinary least squares (OLSE) of individual rates of change (UWLS); weighted average of OLSE (WLS); conditional linear model estimates (CLE), a covariate type estimates proposed by Wu and Bailey (1989); random effect (RE), and joint multivariate RE (JMRE) estimates. The latter method combines a linear RE model for the underlying pattern of the marker with a log-normal survival model for informative drop-out process. The performance of these methods in the presence of missing data completely at random (MCAR), at random (MAR) and non-ignorable (NIM) were compared in simulation studies. Data for the disease marker were generated under the linear random effects model with parameter values derived from realistic examples in HIV infection. Rates of drop-out, assumed to increase over time, were allowed to be independent of marker values or to depend either only on previous marker values or on both previous and current marker values. Under MACR all six methods yielded unbiased estimates of both group mean rates and between group difference. However, the cross-sectional view of the data in the GEE method resulted in seriously biased estimates under MAR and NIM drop-out process. The bias in the estimates ranged from 30 per cent to 50 per cent. The degree of bias in the GEE estimates increases with the severity of non-randomness and with the proportion of MAR data. Under MCAR and MAR all the other five methods performed relatively well. RE and JMRE estimates were more efficient(that is, had smaller variance) than UWLS, WLS and CL estimates. Under NIM, WLS and particularly RE estimates tended to underestimate the average rate of marker change (bias approximately 10 per cent). Under NIM, UWLS, CL and JMRE performed better in terms of bias (3-5 per cent) with the JMRE giving the most efficient estimates. Given that markers are key variables related to disease progression, missing marker data are likely to be at least MAR. Thus, the GEE method may not be appropriate for analysing such longitudinal marker data. The potential biases due to incomplete data require greater recognition in reports of longitudinal studies. Sensitivity analyses to assess the effect of drop-outs on inferences about the target parameters are important. PMID- 11782029 TI - Current and future challenges in the design and analysis of cluster randomization trials. AB - Randomized trials in which the unit of randomization is a community, worksite, school or family are becoming widely used in the evaluation of life-style interventions for the prevention of disease. The increasing interest in adopting a cluster randomization design is being matched by rapid methodological developments. In this paper we describe several of these developments. Brief mention is also made of issues related to economic analysis and to the planning and conduct of meta-analyses for cluster randomization trials. Recommendations for reporting are also discussed. PMID- 11782030 TI - Modification of the sample size and the schedule of interim analyses in survival trials based on data inspections. AB - A method is presented which allows us to adapt the sample size as well as the number and time points of interim analyses to the treatment difference observed at an interim look during the course of a clinical trial with censored survival time as the endpoint. The method allows the inclusion of data inspections during the course of the trial and redesign of the trial on the basis of the observed treatment difference without affecting the type I error risk. Formulae for recalculating the required number of events and the number of further patients to be randomized as a function of the observed hazard rates and the detectable hazard ratio are given. PMID- 11782031 TI - Accounting for correlation and compliance in cluster randomized trials. AB - This paper discusses causal inference with survival data from cluster randomized trials. It is argued that cluster randomization carries the potential for post randomization exposures which involve differentially selective compliance between treatment arms, even for an all or nothing exposure at the individual level. Structural models can be employed to account for post-randomization exposures, but should not ignore clustering. We show how marginal modelling and random effects models allow to adapt structural estimators to account for clustering. Our findings are illustrated with data from a vitamin A trial for the prevention of infant mortality in the rural plains of Nepal. PMID- 11782032 TI - Application of random effect ordinal regression model for outcome evaluation of two randomized controlled trials. AB - Cluster randomization is often used in intervention trials, yet when individuals nested within clusters are considered as the units of analysis for outcome evaluation, it cannot be assumed that the observations are statistically independent. Observations that are not statistically independent also result when repeated measures are taken over time for the same individual. Ignoring clustered observations when performing data analysis can lead to the erroneous conclusion that the intervention under study had a statistically significant effect. Moreover, individual responses are often collected on ordinal scales; thus models for continuous or categorical data are usually not appropriate. We applied a random effect ordinal regression model to data sets from two randomized controlled intervention trials that measured graded scale non-independent responses. The first trial compared two school programmes for AIDS prevention in terms of impact (i.e., changes in the frequency of condom use). The second trial used the MOS-HIV questionnaire to measure the quality of life of new AIDS cases four times over a one-year follow-up period (only results of the role-functioning scale are reported). Regarding the first data set, the effect of the intervention was not significant, and the post-intervention frequency of condom use was mainly attributable to the pre-intervention frequency (p<0.01), with no differences among schools. Regarding the second data set, a borderline significant increase in the role-functioning scale scores was observed over the follow-up period; the results differed only slightly by intervention group; a significant (p<0.01) intra-individual correlation of 0.4 was found. PMID- 11782033 TI - Prospective application of Bayesian monitoring and analysis in an "open" randomized clinical trial. AB - We describe the prospective application of Bayesian monitoring and analysis in an ongoing large multi-centre, randomized trial in which interim results are released to investigators. Substantial variability in prior opinion led us to reject the use of elicited clinical priors for monitoring, in favour of archetypal prior distributions representing reasonable scepticism and enthusiasm. Likelihoods for odds ratios for different covariate values are derived from a logistic regression model, which allows us to incorporate information from prognostic factors without resorting to specialized software. Priors, likelihoods and posterior distributions are regularly reported to both an independent Data Monitoring Committee and the trial investigators. PMID- 11782034 TI - Analysis of ambulatory blood pressure monitor data using a hierarchical model incorporating restricted cubic splines and heterogeneous within-subject variances. AB - Hypertensive disorders of pregnancy are associated with significant maternal and foetal morbidity. Measurement of blood pressure remains the standard way of identifying individuals at risk. There is growing interest in the use of ambulatory blood pressure monitors (ABPM), which can record an individual's blood pressure many times over a 24-hour period. From a clinical perspective interest lies in the shape of the blood pressure profile over a 24-hour period and any differences in the profile between groups. We propose a two-level hierarchical linear model incorporating all ABPM data into a single model. We contrast a classical approach with a Bayesian approach using the results of a study of 206 pregnant women who were asked to wear an ABPM for 24 hours after referral to an obstetric day unit with high blood pressure. As the main interest lies in the shape of the profile, we use restricted cubic splines to model the mean profiles. The use of restricted cubic splines provides a flexible way to model the mean profiles and to make comparisons between groups. From examining the data and the fit of the model it is apparent that there were heterogeneous within-subject variances in that some women tend to have more variable blood pressure than others. Within the Bayesian framework it is relatively easy to incorporate a random effect to model the between-subject variation in the within-subject variances. Although there is substantial heterogeneity in the within-subject variances, allowing for this in the model has surprisingly little impact on the estimates of the mean profiles or their confidence/credible intervals. We thus demonstrate a powerful method for analysis of ABPM data and also demonstrate how heterogeneous within-subject variances can be modelled from a Bayesian perspective. PMID- 11782035 TI - Analysis of recurrent failure times data: should the baseline hazard be stratified? AB - Over the past two decades, a variety of fruitful statistical methods for the analysis of recurrent events has been proposed for the estimation of covariates effect using the Cox proportional hazard model. Besides frailty modelling, two simple trends of modelling have been developed: the first one uses stratification on the rank of the event, whereas the second one, more closely related to Poisson processes theory, does not use stratification. Although they both take into account the correlation of the unit failure times, each of these approaches emphasizes a different aspect of the underlying point process and there is still an ongoing debate concerning the most appropriate method. The aim of this paper is to stress current interests and trends concerning these two approaches. For each model, main statistical methods for estimating the covariates effects are presented. Methods are illustrated and compared in two randomized clinical trials which involve recurrences of severe adverse events following chemotherapy in 938 patients with chronic lymphocytic leukaemia, and recurrences of infectious rhinitis episodes in 327 patients. The discussion, based on the previous examples and on the properties of underlying statistical inference, deals with the appropriateness of the model choice, which is closely related to the data structure. PMID- 11782036 TI - On the use of Cox regression in the presence of an irregularly observed time dependent covariate. AB - We consider the joint modelling of longitudinal and event time data. The longitudinal data are irregularly collected and the event times are subject to right censoring. Most methods described in the literature are quite complex and do not belong to the standard statistical tools. We propose a more practical approach using Cox regression with time-dependent covariates. Since the longitudinal data are observed irregularly, we have to account for differences in observation frequency between individual patients. Therefore, the time elapsed since last observation (TEL) is added to the model. TEL and its interaction with the time-dependent covariate show a strong effect on the hazard. The latter indicates that older recordings have less impact than recent recordings. Pros and cons of this methodology are discussed and a simulation study is performed to study the effect of TEL on the hazard. The fitted Cox model serves as a starting point for the prediction of future patient's events. Our method is applied to a study on chronic myeloid leukaemia (CML) with longitudinal white blood cell counts (WBC) as time-dependent covariate and patient's death as event. PMID- 11782037 TI - Construction of a single global scale for multi-item assessments of the same variable. AB - Complex health-related concepts are commonly measured by means of multi-item scales or questionnaires. As the item scales of an instrument cover different aspects of the same variable, a single global response value is required of the concept to be measured. In this paper, different approaches that take into account the non-metric properties of ordered categorical data when aggregating multi-item scales into global scaling were suggested. A single score of equally important items is easily defined by the median. When the multi-items are constructed to identify the most serious sign of a particular state, the maximum categorical level of the items could be an appropriate single score of the variable. By means of the joint response scheme over two aspects of the same variable, a global scale with an optional number of ordered categories could be defined. Some of the multi-item scales of the Short-Form Health Survey (SF-36) and Euro-QoL were used for illustrations to the proposed approaches. PMID- 11782038 TI - Residual mass histology in testicular cancer: development and validation of a clinical prediction rule. AB - After chemotherapy for metastatic non-seminomatous testicular cancer, surgical resection is a generally accepted treatment to remove remnants of the initial metastases, since residual tumour may still be present (mature teratoma or viable cancer cells). In this paper, we review the development and external validation of a logistic regression model to predict the absence of residual tumour. Three sources of information were used. A quantitative review identified six relevant predictors from 19 published studies (996 resections). Second, a development data set included individual data of 544 patients from six centres. This data set was used to assess the predictive relationships of five continuous predictors, which resulted in dichotomization for two, and a log, square root, and linear transformation for three other predictors. The multiple logistic regression coefficients were reduced with a shrinkage factor (0.95) to improve calibration, based on a bootstrapping procedure. Third, a validation data set included 172 more recently treated patients. The model showed adequate calibration and good discrimination in the development and in the validation sample (areas under the ROC curve 0.83 and 0.82). This study illustrates that a careful modelling strategy may result in an adequate predictive model. Further study of model validity may stimulate application in clinical practice. PMID- 11782039 TI - A comparison of methods for adaptive sample size adjustment. AB - In fixed sample size designs, precise knowledge about the magnitude of the outcome variable's variance in the planning phase of a clinical trial is mandatory for an adequate sample size determination. Wittes and Brittain introduced the internal pilot study design that allows recalculation of the sample size during an ongoing trial using the estimated variance obtained from an interim analysis. However, this procedure requires the unblinding of the treatment code. Since unblinding of an ongoing trial should be avoided whenever possible, there should be some benefit of this design compared with blinded sample size recalculation procedures to justify the unveiling of the treatment code. In this paper, we compare several sample size recalculation procedures with and without unblinding. The simulation results indicate that the procedures behave similarly. In particular, breaking of the blind is not required for an efficient sample size adjustment. We also compare these pure sample size adaptation procedures with study designs which additionally allow for early stopping. Evaluation of the cumulative distribution function of the resulting sample sizes shows that the option for early stopping may lead to lower expectation but generally to a higher variability. The procedures are illustrated by an example of a trial in the treatment of depression. PMID- 11782040 TI - A refined method for the meta-analysis of controlled clinical trials with binary outcome. AB - For the meta-analysis of controlled clinical trials with binary outcome a test statistic for testing an overall treatment effect is proposed, which is based on a refined estimator for the variance of the treatment effect estimator usually used in the random-effects model of meta-analysis. In simulation studies it is shown that the proposed test keeps the prescribed significance level much better than the commonly used tests in the fixed-effects and random-effects model, respectively. Moreover, when using the test it is not necessary to choose between fixed effects and random effects approaches in advance. The proposed method applies in the same way to the analysis of a controlled multi-centre study with binary outcome, including a possible interaction between drugs and centres. PMID- 11782041 TI - Analysis of the infection system of human T-cell leukaemia virus type I based on a mathematical epidemic model. AB - Human T-cell leukaemia virus type I (HTLV-I) is a retrovirus that causes adult T cell leukaemia (ATL). HTLV-I has existed in Japanese people for thousands of years. In order to prevent an epidemic of HTLV-I, it is important to explain the infection system by a mathematical approach. By considering the main infection routes in Japan, that is: (i) mother-to-child transmission; (ii) male (husband) to-female (wife) transmission; and (iii) female (wife)-to-male (husband) transmission, a mathematical model for describing the time-dependent change of the infection proportion can be constructed. An upper bound of the present infection rate per year in male-to-female transmission and that in female-to-male transmission is given by the model, and theoretical results related to HTLV-I infection are also deduced from the mathematical model. A simulation study based on the present model demonstrates the theoretical results relating to the HTLV-I infection. PMID- 11782042 TI - Sensitivity analysis of longitudinal binary quality of life data with drop-out: an example using the EORTC QLQ-C30. AB - Analysing quality of life data (QOL) may be complicated for several reasons. Quality of life data not only involves repeated measures but is also usually collected on ordered categorical responses. In addition, it is evident that not all patients provide the same number of assessments, due to attrition caused by death or other medical reasons. In the recent statistical literature, increasing attention is given to methods which can handle non-continuous outcomes in the presence of missing data. The aim of this paper is to investigate the effect on statistical conclusions of applying different modelling techniques to QOL data generated from an EORTC phase III trial. Treatment effects and treatment differences are of major concern. First, a random-effects model is fitted, relating a binary longitudinal response (derived from the physical functioning scale of the QLQ-C30) to several covariates. In a second approach, marginal models are fitted, retaining the response variable and the mean structure used before. The fitted marginal models only differ with respect to the considered estimation procedure: generalized estimating equations (GEE); weighted generalized estimating equations (WGEE), and maximum likelihood (ML). PMID- 11782043 TI - Towards a curriculum for the consultant biostatistician: identification of central disciplines. AB - The variation in the background of biostatistical consultants is huge. This varying background in formal education complicates communication. It may obscure clients' expectations as well as any discussion on qualifications and registration. To tackle these disadvantages as well as to facilitate the training of a new colleague, we need to find common ground. The aim of this paper is to identify the central disciplines which constitute the foundation of biostatistical consultancy. Any task-aimed curriculum should be based on these disciplines. Curriculum design theory was used to guarantee a logical and rational process. The result is the identification of a sextet of disciplines: applied statistics; methodology; epidemiology; communication; computational science, and personal effectiveness. PMID- 11782044 TI - Intention-to-treat: methods for dealing with missing values in clinical trials of progressively deteriorating diseases. AB - Since it came up in the 1960s, the principle of intention-to-treat (ITT) has become widely accepted for the analysis of controlled clinical trials. In this context the question of how to perform such an analysis in the presence of missing information about the main endpoint is of major importance. Uncritical use of several ad hoc strategies for dealing with missing values is common in the practice of clinical trials. On the other hand, little is known about possible dangers and problems of applying these strategies. We therefore performed a detailed investigation of different methods for dealing with missing values in order to develop recommendations for their practical use. A simulation study was performed investigating possible consequences on type I error and power of applying different methods for dealing with missing values. The simulations were based on a clinical trial of osteoporosis, a progressively deteriorating disease. The strategies examined can be roughly classified into numerical imputation strategies (last observation carried forward, mean and regression based methods) and non-parametric strategies (rank and dichotomization based methods). Different drop-out mechanisms and different types of progression of disease are considered. The type I error increases drastically for the different strategies, especially if the courses of disease vary between treatment groups. The loss in power can be substantial. There is no strategy which is adequate for all different combinations of drop-out mechanisms, drop-out rates and courses of disease over time. For drop-out rates less than 20 per cent and similar courses of disease in the treatment groups, missing values might be replaced by the mean of the other group, or counted as treatment failures after dichotomization of the endpoint. For larger drop-out rates or less similar courses of disease, no adequate recommendations can be given. Because of the drastic consequences of increasing drop-out rates, it has to be a primary goal in clinical trials to keep missing values to a minimum. Unobserved information cannot be reliably regained by any methodological resources. As there are no strategies for universal use, reasons for the choice of a certain method have to be provided when designing and analysing clinical trials. PMID- 11782045 TI - Number needed to treat (NNT): estimation of a measure of clinical benefit. AB - The number needed to treat (NNT) is becoming increasingly popular as an index for reporting the results of randomized trials and other clinical studies. It represents the expected number of patients who must be treated with an experimental therapy in order to prevent one additional adverse outcome event (or, depending on the context, to expect one additional beneficial outcome), compared to the expected event rates under the control therapy. Although NNT is a clinically useful measure, little work has been done on its statistical properties. In this paper, alternative NNT-type measures are defined for use with discrete or continuous data. Estimators and their variances are obtained for these measures in cross-over or parallel group designs. The ideas are illustrated with data on quality of life in asthma patients. PMID- 11782047 TI - Marginal estimation for multi-stage models: waiting time distributions and competing risks analyses. AB - We provide non-parametric estimates of the marginal cumulative distribution of stage occupation times (waiting times) and non-parametric estimates of marginal cumulative incidence function (proportion of persons who leave stage j for stage j' within time t of entering stage j) using right-censored data from a multi stage model. We allow for stage and path dependent censoring where the censoring hazard for an individual may depend on his or her natural covariate history such as the collection of stages visited before the current stage and their occupation times. Additional external time dependent covariates that may induce dependent censoring can also be incorporated into our estimates, if available. Our approach requires modelling the censoring hazard so that an estimate of the integrated censoring hazard can be used in constructing the estimates of the waiting times distributions. For this purpose, we propose the use of an additive hazard model which results in very flexible (robust) estimates. Examples based on data from burn patients and simulated data with tracking are also provided to demonstrate the performance of our estimators. PMID- 11782048 TI - Evaluating inter-hospital variability in mortality rates over time, allowing for time-varying effects. AB - In outcome studies, quality of care in various institutions is typically assessed by comparing observed to expected outcome rates, after adjusting for patients' case-mix factors in logistic regression models. However, differences in patterns of outcome rates over time, especially when there is a distinction between the determinants affecting early and later events, are rarely studied. We use six month mortality after coronary artery bypass graft operation (CABG) as an example. We present a statistically valid approach to estimate expected survival curves for different subgroups, based on a Cox survival model with time-varying effects. Bootstrap confidence intervals around the expected survival curves are constructed. This approach is applied for examining the pattern of deviation of high-mortality hospitals after CABG. Implications for quality assessment in comparative outcome studies are discussed. PMID- 11782049 TI - Sample size requirements for matched case-control studies of gene-environment interaction. AB - Consideration of gene-environment (GxE) interaction is becoming increasingly important in the design of new epidemiologic studies. We present a method for computing required sample size or power to detect GxE interaction in the context of three specific designs: the standard matched case-control; the case-sibling, and the case-parent designs. The method is based on computation of the expected value of the likelihood ratio test statistic, assuming that the data will be analysed using conditional logistic regression. Comparisons of required sample sizes indicate that the family-based designs (case-sibling and case-parent) generally require fewer matched sets than the case-control design to achieve the same power for detecting a GxE interaction. The case-sibling design is most efficient when studying a dominant gene, while the case-parent design is preferred for a recessive gene. Methods are also presented for computing sample size when matched sets are obtained from a stratified population, for example, when the population consists of multiple ethnic groups. A software program that implements the method is freely available, and may be downloaded from the website http://hydra.usc.edu/gxe. PMID- 11782050 TI - An extension of the continual reassessment method using decision theory. AB - The primary goal of a phase I trial is to find the maximally tolerated dose (MTD) of a treatment. The MTD is usually defined in terms of a tolerable probability, q(*), of toxicity. Our objective is to find the highest dose with toxicity risk that does not exceed q(*), a criterion that is often desired in designing phase I trials. This criterion differs from that of finding the dose with toxicity risk closest to q(*), that is used in methods such as the continual reassessment method. We use the theory of decision processes to find optimal sequential designs that maximize the expected number of patients within the trial allocated to the highest dose with toxicity not exceeding q(*), among the doses under consideration. The proposed method is very general in the sense that criteria other than the one considered here can be optimized and that optimal dose assignment can be defined in terms of patients within or outside the trial. It includes as an important special case the continual reassessment method. Numerical study indicates the strategy compares favourably with other phase I designs. PMID- 11782051 TI - A testing procedure for survival data with few responders. AB - In the course of designing a clinical trial, investigators are often faced with the possibility that only a fraction of the patients will benefit from the experimental treatment. A proper clinical trial design requires prospective specification of the testing procedures to be used in the analysis. In the absence of reliable prognostic factors capable of identifying the appropriate subset of patients, there is a need for a test procedure that will be sensitive to a range of possible fractions of responders. Focusing on survival data, we propose guidelines for selecting a proper test procedure based on the anticipated proportion of responding patients. These guidelines suggest that the logrank test should be used when the fraction of responders is expected to be greater than 0.5, otherwise procedures based on weighted linear rank tests are preferable. Overall this approach provides good power properties when the treatment affects only a small proportion of patients while protecting against substantial loss of power when all patients are affected. Use of the procedure is illustrated with data from two published randomized studies. PMID- 11782052 TI - Two goodness-of-fit tests for logistic regression models with continuous covariates. AB - Assessing goodness-of-fit in logistic regression models can be problematic, in that commonly used deviance or Pearson chi-square statistics do not have approximate chi-square distributions, under the null hypothesis of no lack of fit, when continuous covariates are modelled. We present two easy to implement test statistics similar to the deviance and Pearson chi-square tests that are appropriate when continuous covariates are present. The methodology uses an approach similar to that incorporated by the Hosmer and Lemeshow goodness-of-fit test in that observations are classified into distinct groups according to fitted probabilities, allowing sufficient cell sizes for chi-square testing. The major difference is that the proposed tests perform this grouping within the cross classification of all categorical covariates in the model and, in some situations, allow for a more powerful assessment of where model predicted and observed counts may differ. A variety of simulations are performed comparing the proposed tests to the Hosmer-Lemeshow test. PMID- 11782053 TI - A model for foetal growth and diagnosis of intrauterine growth restriction. AB - A model for foetal growth is developed and used to construct tools for diagnosis of intrauterine growth restriction. Foetal weight estimates are first transformed to normally distributed z-scores. The covariance structure over gestational ages is then estimated using a novel regression model. The diagnostic tools include individual growth curves with error bounds, probabilities to assess whether a foetus is small for its gestational age, and residual scores to determine whether current growth rates are unusual. The methods were developed sing data from 13593 ultrasound examinations involving 7888 foetal subjects. The model shows that median foetal growth velocity increases up to a gestational age of 35 weeks and then decreases during the final weeks of pregnancy. When growth is expressed as change in log weight, or equivalently as change proportional to current weight, the model reveals a constant deceleration as gestational age increases from 14 to 42 weeks. PMID- 11782054 TI - Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients. AB - Chronic rejection in lung transplant recipients is monitored by repeated measurement of forced expiratory volume in one second (FEV1). This marker is measured at irregular intervals and is also affected by covariates and short-term fluctuation. This paper describes the use of hidden Markov models for the underlying staged functional decline. Maximum likelihood methods are used to simultaneously estimate disease progression rates and the effects of mismeasurement and covariates. PMID- 11782055 TI - Item response models for joint analysis of quality of life and survival. AB - A complication when assessing quality of life data longitudinally is that in many trials a substantial percentage of patients die before completing all of the assessments. Furthermore, a patient's risk of dying might be predicted by his current quality of life. This suggests jointly modelling quality of life and survival, and using this combined information to summarize the outcome. The aim of this paper is to address the complicated issues, such as death, present in analysing multiple-item ordinal quality of life data in clinical trials while recognizing the psychometric properties of the quality of life instrument being used. This is done by combining an item response model and Cox's proportional hazard model, where a latent variable process for quality of life determines the probability of selecting various options on quality of life items, and also serves as a time-dependent covariate in the survival model. We accomplish this by using Markov chain Monte Carlo methods to obtain parameter estimates. Then we compute a summary measure, area-under-QOL curve, to compare the efficacy of the treatments. The methods are illustrated with analysis of data from the Vesnarinone trial of patients with severe heart failure, in which quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire. PMID- 11782056 TI - Covariance models for nested repeated measures data: analysis of ovarian steroid secretion data. AB - We consider several covariance models for analysing repeated measures data from a study of ovarian steroid secretion in reproductive-aged women. Urinary oestradiol and serum oestrogen were repeatedly observed over three or four menstrual periods, each period separated by one year. For each menstrual period, daily first morning urine specimens were collected 8 to 18 times, and serum specimens 2 to 5 times. Thus, measurements were repeatedly observed over menstrual cycle days within menstrual periods. Owing to missing observations, the number of observations differed from subject to subject. In this study, there were two repeat factors: menstrual cycle day and menstrual period. The first repeat factor, cycle day, is nested within the second repeat factor, menstrual period. In analysing these nested repeated measures data, the correlation structure should be modelled that will account for both repeat factors. We present several covariance models for defining appropriate covariance structures for these data. PMID- 11782057 TI - On the inappropriateness of an EM algorithm based procedure for blinded sample size re-estimation. AB - When planning a clinical trial the sample size calculation is commonly based on an a priori estimate of the variance of the outcome variable. Misspecification of the variance can have substantial impact on the power of the trial. It is therefore attractive to update the planning assumptions during the ongoing trial using an internal estimate of the variance. For this purpose, an EM algorithm based procedure for blinded variance estimation was proposed for normally distributed data. Various simulation studies suggest a number of appealing properties of this procedure. In contrast, we show that (i) the estimates provided by this procedure depend on the initialization, (ii) the stopping rule used is inadequate to guarantee that the algorithm converges against the maximum likelihood estimator, and (iii) the procedure corresponds to the special case of simple randomization which, however, in clinical trials is rarely applied. Further, we show that maximum likelihood estimation leads to no reasonable results for blinded sample size re-estimation due to bias and high variability. The problem is illustrated by a clinical trial in asthma. PMID- 11782058 TI - Group sequential monitoring of years of life saved with paired censored survival data. AB - This research develops non-parametric methodology for sequential monitoring of paired time-to-event data when comparing years of life saved, or years where any unpleasant outcome is delayed, is of interest. The recommended family of test statistics uses integrated differences in survival estimates that are available during the study period, where adjustments are made for dependence in the survival and censoring outcomes under comparison. In the context of paired censored survival data, the joint asymptotic closed form distribution of these sequentially monitored test statistics is developed and shown to have a dependent increments structure. Simulations verifying nice operating characteristics of the proposed monitoring methods also reveal consequences of ignoring an underlying paired data structure in terms of size and power properties. A motivating example is also presented via the Early Treatment Diabetic Retinopathy Study, which did not have methods available for sequentially monitoring paired censored survival data at the time. PMID- 11782059 TI - Analysis of ulcer data using hierarchical generalized linear models. AB - In multi-centre clinical trials, heterogeneities in individual hospital treatment effects can be modelled as random effects. Estimates of the individual hospital treatment effects and estimate of the mean treatment effect, allowing for the presence of overall hospital differences, are required, together with some measure of their uncertainty. Systematic inferences from the hierarchical likelihood are now possible, using hierarchical generalized linear models. We show how to construct profile likelihoods for the treatment effects of individual hospitals. PMID- 11782060 TI - Complete imputation of missing repeated categorical data: one-sample applications. AB - Longitudinal studies with repeated measures are often subject to non-response. Methods currently employed to alleviate the difficulties caused by missing data are typically unsatisfactory, especially when the cause of the missingness is related to the outcomes. We present an approach for incomplete categorical data in the repeated measures setting that allows missing data to depend on other observed outcomes for a study subject. The proposed methodology also allows a broader examination of study findings through interpretation of results in the framework of the set of all possible test statistics that might have been observed had no data been missing. The proposed approach consists of the following general steps. First, we generate all possible sets of missing values and form a set of possible complete data sets. We then weight each data set according to clearly defined assumptions and apply an appropriate statistical test procedure to each data set, combining the results to give an overall indication of significance. We make use of the EM algorithm and a Bayesian prior in this approach. While not restricted to the one-sample case, the proposed methodology is illustrated for one-sample data and compared to the common complete-case and available-case analysis methods. PMID- 11782061 TI - Non-linear hierarchical models for monitoring compliance. AB - As biomarkers transformable by specific drug agents increasingly become available, so their usefulness also increases for monitoring compliance in clinical and prevention trials, and for subsequent monitoring in the general population if a treatment is found successful. Marker levels measured over the course of a treatment yield a longitudinal trajectory that is typically non linear, with varying velocities during the phase-in and steady-state periods of treatment, followed by decays back to normal in the presence of non-compliance. There is often considerable between-individual variability both in the mean parameters of the trajectory and the variability over time. An example is the biomarker mean corpuscular volume (MCV), which increases by 20 per cent from the drug zidovudine (AZT), and has been used to monitor compliance to AZT. Using MCV data from a previous AIDS clinical trial as an example, we describe a non-linear hierarchical growth model suitable for biomarkers that exhibit sigmoidal and/or asymptotic growth behaviour and show how such models can be supplemented with a change-point to identify potential times of non-compliance. We perform a fully Bayesian analysis to obtain a variety of posterior summaries for the behaviour of the longitudinal trajectory and the times of non-compliance, and describe how to obtain predictions of non-compliance for new individuals. PMID- 11782062 TI - Tests for equivalence or non-inferiority for paired binary data. AB - Assessment of therapeutic equivalence or non-inferiority between two medical diagnostic procedures often involves comparisons of the response rates between paired binary endpoints. The commonly used and accepted approach to assessing equivalence is by comparing the asymptotic confidence interval on the difference of two response rates with some clinical meaningful equivalence limits. This paper investigates two asymptotic test statistics, a Wald-type (sample-based) test statistic and a restricted maximum likelihood estimation (RMLE-based) test statistic, to assess equivalence or non-inferiority based on paired binary endpoints. The sample size and power functions of the two tests are derived. The actual type I error and power of the two tests are computed by enumerating the exact probabilities in the rejection region. The results show that the RMLE-based test controls type I error better than the sample-based test. To establish an equivalence between two treatments with a symmetric equivalence limit of 0.15, a minimal sample size of 120 is needed. The RMLE-based test without the continuity correction performs well at the boundary point 0. A numerical example illustrates the proposed procedures. PMID- 11782063 TI - Standardization using the harmonically weighted ratios: internal and external comparisons. AB - Standardization of rates is a basic tool for epidemiologists. The most frequently used methods are the 'direct standardization' (with summary index of comparative mortality figure, CMF) and the 'indirect standardization' (with summary index of standardized mortality ratio, SMR). The CMF facilitates a valid comparison between populations or across time periods, yet, it suffers from the problem of instability. By contrast, the SMR is stable and can be used for external comparison. However, it cannot guarantee a valid internal comparison. In this paper, the author proposes a new standardized measure, the 'harmonically weighted ratio' (HWR). The HWR can be used for external as well as internal comparisons- with the assumption of rate-ratio homogeneity, or with heterogeneity but dominance of one population over another. Simulation shows that its performance in terms of pairwise comparisons is the best among the three methods or compares favourably to that of the SMR. The author also examines the behaviours of the HWR when used for hypothesis testing (the 'HWR test'). The HWR can be considered for standardization when the purpose of the standardization is solely for comparison and when the universe of the comparisons can be clearly defined. PMID- 11782064 TI - A local likelihood proportional hazards model for interval censored data. AB - We discuss the use of local likelihood methods to fit proportional hazards regression models to right and interval censored data. The assumed model allows for an arbitrary, smoothed baseline hazard on which a vector of covariates operates in a proportional manner, and thus produces an interpretable baseline hazard function along with estimates of global covariate effects. For estimation, we extend the modified EM algorithm suggested by Betensky, Lindsey, Ryan and Wand. We illustrate the method with data on times to deterioration of breast cosmeses and HIV-1 infection rates among haemophiliacs. PMID- 11782065 TI - Bias adjustment in analysing longitudinal data with informative missingness. AB - The recent biostatistical literature contains a number of methods for handling the bias caused by 'informative censoring', which refers to drop-out from a longitudinal study after a number of visits scheduled at predetermined intervals. The same or related methods can be extended to situations where the missing pattern is intermittent. The pattern of missingness is often assumed to be related to the outcome through random effects which represent unmeasured individual characteristics such as health awareness. To date there is only limited experience with applying the methods for informative censoring in practice, mostly because of complicated modelling and difficult computations. In this paper, we propose an estimation method based on grouping the data. The proposed estimator is asymptotically unbiased in various situations under informative missingness. Several existing methods are reviewed and compared in simulation studies. We apply the methods to data from the Wisconsin Diabetes Registry Project, a longitudinal study tracking glycaemic control and acute and chronic complications from the diagnosis of type I diabetes. PMID- 11782066 TI - Cure model analysis in cancer: an application to data from the Children's Cancer Group. AB - The most commonly used statistical methods for evaluating treatment or prognostic effects on cancer outcome--the logrank test and Cox regression analysis--rely on the proportional hazards (PH) assumption in that they have maximal power in this circumstance. Implicitly, these methods emphasize covariate effects on failure times rather than their effects on the proportion of long-term survivors ('cures'), which may be of equal or primary interest. In paediatric cancer, treatment has progressed dramatically in recent decades, and in many diagnoses cures are obtained in a large fraction of patients. A primary focus of clinical research is therefore the achievement of cure. Parametric cure model (PCM) analysis, introduced 50 years ago, is arguably better suited to the analytic requirements of clinical research in paediatric and other cancers where cure is achieved. In this paper two classes of PCMs are described and used to analyse examples from the Children's Cancer Group. These are compared to analyses using Cox regression analysis. Results from PCM analyses are similar or identical to Cox regression analysis when the PH assumption is appropriate. When it is not, PCMs can provide a coherent way to investigate and report covariate effects on the proportion cured separately from their effect on time to failure. Despite their reliance on explicit parametric forms, PCMs often provide a good description of cancer outcome, and are insensitive to lack of fit provided that follow-up is sufficient. PMID- 11782067 TI - Residual-based tree-structured survival analysis. AB - Extensions of various non-parametric regression techniques (for example, additive models, trees, MARS) have been devised for right censored survival data. These approaches directly handle the difficulties posed by censoring. However, it is possible to bypass these difficulties by utilizing standard non-parametric regression procedures applied with (say) martingale residuals as outcome. Analytic correspondences between the direct and residual-based approaches have been established for additive models while more qualitative comparisons have been provided for MARS. Here we develop such correspondences for tree-structured regression. In particular, we provide an analytic relationship between logrank and martingale residual sum-of-squares split functions that explains the widely observed similarity of the resultant trees. Further investigation is provided by simulation and an illustrative example using time to AIDS with data deriving from a Western Australian HIV cohort study. PMID- 11782068 TI - Introduction to the biology of regeneration in echinoderms. PMID- 11782069 TI - Autotomy as a prelude to regeneration in echinoderms. AB - 'Autotomy' refers to the adaptive detachment of animal body parts where this serves a defensive function, is achieved by an intrinsic mechanism, and is nervously mediated. With regard to each echinoderm class, this article itemises those structures that are autotomous, evaluates the extent to which autotomy precedes regeneration in natural populations, reviews current knowledge of the morphology of autotomy planes and mechanisms that effect fracture at autotomy, and comments on autotomy-related issues arising from studies of the cellular events of regeneration. Each autotomy plane can be regarded as an assemblage of breakage zones traversing the individual anatomical components of the autotomous structure. In any one autotomy plane some breakage zones are permanent sites of weakness that are fractured by external forces and some are potential sites of weakness that undergo a loss of tensile strength only at the time of autotomy. The latter occur predominantly in mutable collagenous structures, although there are a few examples of muscles that undergo an endogenous rupturing process. Available evidence indicates that autotomy is by far the commonest proximate cause of structural loss in echinoderms. Most echinoderm regeneration is therefore necessitated by autotomy and proceeds from the retained side of a fractured autotomy plane. Due to a lack of relevant research there is as yet little evidence for or against the presence of specific regeneration-promoting adaptations at autotomy planes, although it is argued that an autotomy plane designed primarily to effect rapid detachment would by itself increase regenerative efficiency. PMID- 11782070 TI - Fossil record of echinoderm regeneration with special regard to crinoids. AB - Regeneration of skeletal parts of fossil echinoderms is reviewed. Among regenerations of various fossil echinoderms, those of crinoids are most common and many examples have been reported. Mesozoic and Cenozoic crinoids, the subclass Articulata, are characterized by the dominance of muscular articulations in the arms and they have only a small number of ligamentary articulations in localized positions that are specialized for autotomy. The dominance of muscular articulations is most conspicuous in the family Isocrinidae and comatulid (stalkless) crinoids. Most of the regenerated arms of articulate crinoids start on this ligamentary articulation. In contrast, most Paleozoic crinoids have many more ligamentary articulations and fewer muscular articulations in their arms than the Mesozoic to Recent crinoids. The ligamentary articulations of Paleozoic crinoids were probably not capable of autotomy. Fossil and recent stalked crinoids provide data on the degree and style of regeneration after loss of body parts. If the aboral nerve center in the basal part of crown is retained, the entire calyx and arms can be regenerated. In contrast, if the aboral nerve center is lost and only the stalk is preserved, some skeletal parts can only be generated imperfectly and irregularly. This type of imperfect regeneration is better termed as overgrowth. PMID- 11782071 TI - Microscopic overview of crinoid regeneration. AB - Crinoids are well known for their striking regenerative potential and can rapidly and completely regenerate arms lost following self-induced or traumatic amputation. Thus they provide a valuable experimental model for investigation of the regenerative process from the macroscopic to the molecular level. In these last years we have studied in detail the overall process of arm regeneration in the comatulid Antedon mediterranea. This phenomenon can be described on the whole as a typical blastemal regeneration in which new structures develop from migratory pluripotential, actively proliferating cells in the presence of presumptive regulatory factors. The overall process can be subdivided into three main phases: a repair phase, an early regenerative phase, and an advanced regenerative phase, whose crucial aspects are related to common fundamental mechanisms such as cell migration and proliferation, intervention of stem cells and/or dedifferentiated cells, contribution of putative growth factors, particularly in terms of specific neurally derived factors, and mechanisms of pattern formation. This article focuses on the main aspects of the phenomenon and gives a brief account of the most recent and relevant results. Our approach employs classical methods of light (LM) and electron (TEM and SEM) microscopy, immunocytochemistry, and histofluorescence on experimentally induced arm regenerations of standard or abnormal type obtained in significantly different experimental conditions, including extreme mutilations (explants) or exposure to pseudo-estrogenic environmental contamination. PMID- 11782072 TI - Regeneration of spines and pedicellariae in echinoderms: a review. AB - Morphogenesis of tissues during regeneration of echinoderm spines and pedicellariae is reviewed. Regeneration of the skeleton is rather well documented while that of associated soft tissues is poorly investigated. In particular, little information is available on the early regeneration stages which follow wound healing. From the available information, it is suggested that regeneration of broken spines proceeds through a morphallactic process of which the organizational information, as well as the involved cells, lies in the stump. In contrast, regeneration of removed spines and pedicellariae may depend on an epimorphic process whose organizational information could be located in the mutable connective tissue that joins the appendage to the main body wall. PMID- 11782073 TI - Visceral regeneration in holothurians. AB - Holothurians, or sea cucumbers, exhibit two processes that have intrigued biologists for decades: autotomy and regeneration. Autotomy includes the loss of body parts by evisceration or fission, and regeneration is the extraordinary process by which the lost organs are replaced. In this article, we review the literature on evisceration, transection, and visceral regeneration in holothurians and compare these processes in different orders and lower taxa. Focusing mainly on the digestive tube, we analyze regeneration from a cellular perspective, considering especially the origin, migration, and proliferation of the cellular components of the regenerated organ. The data highlight the most interesting aspects of holothurian regeneration and indicate those critical problems requiring new information and new approaches. PMID- 11782074 TI - Muscle regeneration in holothurians. AB - The muscle system of holothurians includes visceral (coelomic epithelium) and somatic (longitudinal muscle bands, retractors of aquapharyngeal complex) musculature. Visceral musculature regeneration is achieved by the transformation of myoepithelial cells via their dedifferentiation, migration, proliferation, and redifferentiation. During somatic muscle regeneration the new muscle bundles are formed due to dedifferentiation, migration, and immersion of the coelomic epithelial cells into the connective tissue. While submerging, the epithelial cells transform into myocytes and begin to produce myofibrils in their cytoplasm. Concomitantly, a basal lamina is formed around the group of myogenic cells, separating them from the surrounding extracellular matrix. The myohistogenesis is accompanied by a conspicuous DNA-synthetic activity. Proliferation is insignificant and seems to be of no essential importance for muscle regeneration. The synthesis of DNA followed by no cytokinesis results in an increase in the amount of DNA of myocyte nuclei. PMID- 11782075 TI - Regeneration in echinoderm larvae. AB - The ability of echinoderms to regenerate missing body parts has been a subject of interest to scientists for many years. Asexual reproduction (by fission or budding) is a phenomenon that involves regeneration of missing structures. Although asexual reproduction and regeneration have been the focus of many studies in adult echinoderms, there have been comparatively fewer studies examining these phenomena in echinoderm larvae, and most of these have been conducted in the last few years. In this article we review regeneration in larval echinoderms. We also discuss larval asexual reproduction. PMID- 11782076 TI - Molecular approach to echinoderm regeneration. AB - Until very recently echinoderm regeneration research and indeed echinoderm research in general has suffered because of the lack of critical mass. In terms of molecular studies of regeneration, echinoderms in particular have lagged behind other groups in this respect. This is in sharp contrast to the major advances achieved with molecular and genetic techniques in the study of embryonic development in echinoderms. The aim of our studies has been to identify genes involved in the process of regeneration and in particular neural regeneration in different echinoderm species. Our survey included the asteroid Asterias rubens and provided evidence for the expression of Hox gene homologues in regenerating radial nerve cords. Present evidence suggests: 1) ArHox1 expression is maintained in intact radial nerve cord and may be upregulated during regeneration. 2) ArHox1 expression may contribute to the dedifferentiation and/or cell proliferation process during epimorphic regeneration. From the crinoid Antedon bifida, we have been successful in cloning a fragment of a BMP2/4 homologue (AnBMP2/4) and analysing its expression during arm regeneration. Here, we discuss the importance of this family of growth factors in several regulatory spheres, including maintaining the identity of pluripotent blastemal cells or as a classic skeletal morphogenic regulator. There is clearly substantial scope for future echinoderm research in the area of molecular biology and certain aspects are discussed in this review. PMID- 11782077 TI - Invasive squamous-cell carcinoma in ThinPrep specimens: diagnostic clues in the cellular pattern. AB - Despite the increasing utilization of the ThinPrep Pap Test (TP), limited data exist regarding the cytomorphologic features and patterns of invasive squamous cell carcinoma in TP specimens. We analyzed a series of TP specimens from patients with histologically confirmed invasive squamous carcinomas of the cervix. Patients with biopsy-proven invasive squamous-cell carcinoma of the cervix with a TP cervical cytologic specimen within the previous 2 mo were identified. The TP slides were analyzed for overall cellularity (percent circle coverage by epithelial cells), tumor cellularity, tumor diathesis, inflammation, coexistent dysplasia, and keratinization. Tumor cellularity was defined as <5%, 5 50%, and >50% of slide cellularity. In all 13 cases that were identified, a cytologic diagnosis of either invasive squamous-cell carcinoma or suspicious for invasive squamous-cell carcinoma was made. In 7/13 cases (54%), epithelial cells covered <40% of the slide circle. Epithelial cells covered >40% of the slide circle in 6/13 cases (46%). Tumor cellularity covered <5% of the slide circle in 4/13 cases (31%), 5-50% in 7/13 cases (54%), and >50% in 2/13 cases (15%). A tumor diathesis was present in 12/13 cases (92%). Inflammation was absent in 1/13 cases (8%), mild in 8/13 cases (62%), moderate in 2/13 cases (15%), and severe in 1/13 cases (8%). Coexistent dysplasia was identified in 12/13 cases (92%). Keratinization was identified in 9/13 specimens (69%). In the vast majority of patients, a diagnosis of squamous-cell carcinoma was rendered on the TP cervical specimen, despite a pattern of decreased cell coverage. It could be hypothesized that tumor diathesis and inflammation may be the etiology for decreased cellularity by blocking filter coverage by epithelial cells. This cellular pattern with diathesis in the ThinPrep smear may be a useful clue to look carefully for diagnostic cells of squamous-cell carcinoma. PMID- 11782078 TI - Role of flow cytometry in the diagnosis of lymphadenopathy in children. AB - To evaluate the combination of fine-needle aspiration (FNA) and flow cytometric immunophenotyping (FCI) in the diagnosis of lymphadenopathy in children, we reviewed a total of 71 FNA specimens from pediatric patients with persistent lymphadenopathy. Two cases were deemed inadequate. In the remaining 69 cases, 54 (78%) were diagnosed as benign lesions, 9 (13%) as Hodgkin's lymphoma, 4 (6%) as non-Hodgkin's lymphoma or leukemic infiltrate, and 2 as metastatic tumors. Of the 69 cases, 25 cases (38%) were diagnosed based on cytomorphology alone, 30 (43%) by combined cytomorphology and FCI, and 19 (28%) by surgical biopsy. In conclusion, FNA is an easy, safe, and reliable procedure in the diagnosis of lymphadenopathy in children. In difficult cases, FCI can be used to exclude non Hodgkin's lymphomas. PMID- 11782079 TI - Well-differentiated villoglandular adenocarcinoma of the uterine cervix: cytomorphologic observation of five cases. AB - We retrospectively examined the cytologic findings of well-differentiated villoglandular adenocarcinoma (VGA) treated in our hospital. Cervical smears of four cases and a touch preparation of another case of VGA formed the materials for the study. The cytologic features were correlated with the histomorphology of VGA. Architecturally, long slender papillae and cohesive branching epithelial sheets with smooth borders and a lack of feathery edge were observed. Crowding and overlapping of nuclei were noted. The nuclei were uniform, small, and round to oval-shaped, with evenly distributed granular chromatin. Nucleoli were absent or inconspicuous. Mitoses were occasionally seen in all but one case. As the features of VGA are distinctive, the diagnosis could be possible on cytological grounds. Examination of cervical smears would be helpful for an early diagnosis of VGA or to suggest the coexistence of other neoplastic components. PMID- 11782080 TI - Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure. AB - The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period. PMID- 11782081 TI - Reproducibility of cervicovaginal ThinPrep cellularity assessment. AB - Criteria for judging the squamous cellularity adequacy of cervicovaginal ThinPreps using cell counts in representative fields have been proposed. We compared the interobserver reproducibility in the designation of ThinPreps as satisfactory (SAT), satisfactory but limited by (SBLB), or unsatisfactory (UNS) for interpretation. Three reviewers independently assessed 145 cervicovaginal ThinPreps accessioned from 1997-1999 at the University of Kentucky cytopathology laboratory. Scant specimens were retrieved by computer search and more cellular specimens were added to make 145. Adjacent fields on a diameter including center at 10x and 40x were counted for sufficiently preserved and unobscured cells. A specimen was designated UNS if four or more fields at 10x had less than 10 squamous cells, and SBLB if four or more fields at 40x had less than five squamous cells. All three observers agreed on the adequacy designation in 76% of cases and the overall kappa was 0.73 (near excellent). Complete interobserver agreement was present in 86% (63/73) of UNS cases, 79% (33/42) of SAT, but only 47% (14/30) of SBLB slides. When SBLB and UNS categories were combined, the discrimination from the SAT category was excellent (kappa = 0.87) with pairwise k values of 0.94-0.97. In conclusion, adjacent field cell count methods to judge ThinPrep cellularity provide near excellent interobserver reproducibility. While we have designated both UNS and SBLB adequacy categories, criteria could easily be revised to set one threshold to separate SAT and UNS ThinPreps. PMID- 11782082 TI - Dirofilariasis of breast: report of two cases diagnosed by fine-needle aspiration biopsy. AB - We report on 2 cases of dirofilariasis of the breast occurring in adult Chinese females residing in Hong Kong. The diagnosis was made by fine-needle aspiration biopsies. The direct smears contained numerous acute inflammatory cells, including eosinophils. A partially necrotic adult nematode of about 400-450 microm in diameter was identified in the cell-block sections of each case. The worm was characterized by a thick cuticle with longitudinal cuticular ridges and fine transverse surface striations, abundant somatic muscle, an intestine, and a reproductive tube or uterus. The morphologic features of this round worm were most compatible with those of Dirofilaria repens. While the clinical and radiologic findings of dirofilariasis of the breast are nonspecific and mimic those of breast neoplasms or inflammatory conditions, a definitive diagnosis is possible with fine-needle aspiration biopsy. A correct diagnosis of dirofilariasis may help to spare patients from unnecessary medical and surgical interventions. PMID- 11782083 TI - Diagnostic difficulties in spontaneous infarction of a fibroadenoma in an adolescent: case report. AB - Spontaneous infarction is an uncommon complication occurring in fibroadenoma of the breast. Although infarction following fine-needle aspiration has been reported in the literature, to the best of our knowledge this is the first reported case where infarction was encountered on first-time aspiration. It is necessary to distinguish infarcted fibroadenoma from mastitis, duct ectasia, mammary tuberculosis, and carcinoma on cytology smears. Lack of knowledge of this entity may lead to an erroneous diagnosis of inflammatory lesion or carcinoma. We report the first case of cytological and histological findings in spontaneous infarction of fibroadenoma in 13-yr-old female. PMID- 11782084 TI - Fine-needle aspiration cytology of benign and malignant adenomyoepithelioma: report of two cases. AB - Cytological features of a malignant spindle-cell variant and a benign tubular variant of adenomyoepithelioma were examined to improve diagnosis of this tumor. Fine-needle aspiration cytology, of both a malignant and a benign case, characterized cellular and cohesive cell clusters composed of epithelial and myoepithelial cells. The smears of the malignant case were rich in spindle-shaped myoepithelial cells, admixed with a few epithelial cells. In about a fourth of the clusters, atypical cells with enlarged hyperchromatic nuclei and prominent nucleoli comprised more than 20% of cells. The smears of the benign case were composed of tubular epithelial cells surrounding one to several layers of myoepithelial cells with clear cytoplasm. Mild atypia was occasionally noticed. A review of the literature showed that a cytological diagnosis of malignancy is not warranted, if nuclear atypia is not generally severe. Focal severe atypia is not definitively indicative of benignity or malignancy. PMID- 11782085 TI - Abnormal cervicovaginal smears due to endometriosis: a continuing problem. AB - Endometriosis may be challenging when identified on cervicovaginal smears (CVS), leading to an incorrect interpretation of high-grade squamous intraepithelial lesion (HSIL), or atypical glandular cells of undetermined significance (AGUS) including adenocarcinoma in situ (AIS). Awareness of cervical endometriosis, particularly in predisposed patients, is crucial for a correct diagnosis. While cervical endometriosis has been reported to be a diagnostic pitfall of glandular abnormalities, its characteristic features are still not well-established. This may partially be attributed to the varied cytomorphologic features endometriosis shows, depending on menstrual cycle hormonal changes. We describe our experience with three examples where CVS were interpreted as either AGUS or HSIL, which led to a hysterectomy in 2 of 3 patients. Cervical endometriosis needs to be considered with other well-known benign conditions that mimic glandular abnormalities, including cervicitis, tubal metaplasia, lower uterine segment sampling, and microglandular hyperplasia. Published series and our own experience lead us to suggest that these smears will continue to present diagnostic difficulties. PMID- 11782086 TI - Diagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytology. AB - The thyroid fine-needle aspiration (FNA) diagnosis of "follicular neoplasm" does not differentiate between a benign and malignant tumor. Often cases diagnosed as "follicular or Hurthle-cell neoplasm" undergo surgical excision for further characterization. The aim of this study was to identify clinical features that may help in predicting malignancy in patients with an FNA diagnosis of follicular neoplasm. One hundred eighty-four cases in 167 patients were diagnosed as "follicular neoplasm" among 1,024 thyroid FNA evaluated with on-site interpretation from 1998-2000. The cases were evaluated for the following variables: histologic diagnosis, age, sex, and size of the nodule. One hundred thirty-nine patients were female, and 28 were male (age range, 23-80 yr). Among 122 patients (67%) undergoing surgical excision (lobectomy, 96; total thyroidectomy, 26), malignancy was identified in 37 cases (31%). Nonpapillary (follicular/Hurthle) carcinoma was diagnosed in 11 (9%), follicular variant of papillary carcinoma in 25, and medullary carcinoma in 1 case. The risk of malignancy was greater in males (47% vs. 29%, P < 0.0004) than females, in nodules measuring 3 cm or more (55% vs. 23%, P < 0.0001), than in nodules measuring less than 3 cm, and in patients 40 or more yr old (20% vs. 10%, P = 0.0001) than in patients younger than 40 years. The diagnosis "follicular neoplasm" is indeterminate, and the majority of cases (70% in the current study) are benign. However, clinical features, including gender, nodule size, and age, can be a part of the decision analysis in selecting patients for surgery. PMID- 11782088 TI - Cervical biopsy/cytology correlation data can be collected prospectively and shared clinically. AB - Cervical cytology (Cy) and biopsy (Bx) correlation is used by institutions for the evaluation of their cytodiagnostic capabilities as a part of overall laboratory quality improvement (QI). However, the data obtained from correlation are not routinely included in most surgical pathology (SP) reports. Our laboratory's procedure is to include the correlation of the patient's previous (most recent) cytology smear in the surgical pathology report of all/any gynecologic surgical pathology specimens. We reviewed this process for the time period between July 1998-June 1999. Any noncorrelating cases were assigned a correlation review code by the reviewing cytopathologist: major Cy diagnostic error (DE1), minor Cy diagnostic error (DE2), Cy sampling error (Cy SE), or biopsy sampling error (Bx SE). Of 3,486 cases reviewed, 3,229 cases were satisfactory for correlation studies. Concordant results were found in 86.9%. Cy DE1 due to either Cy screening or interpretation errors or both were found in 0.2% (n = 7) of all cases, while Cy DE2 due to the same were found in 1% (n = 32). Bx SE accounted for discrepancies in 6.8% (n = 220) of all cases, while 5.1% (n = 164) of the total cases were discrepancies due to Cy SE. Follow-up Bx was available in 97.2% (n = 214) of the Bx SE, and showed 16.4% (n = 35) to be major discrepancies and 83.6% (n = 179) to be minor discrepancies. Cervical Cy/Bx correlation is useful for the evaluation of a laboratory's QI. It is also useful for the identification of either Cy or Bx SE. While QI data exist as "internal use only" documents, SE data (as part of the CC (correlation comment) included in SP reports) are vital to a specific/given patient. Bx SE was identified in 6.3% of our patients, indicating a possible need for rebiopsy. This type of QI data may be shared clinically, and may direct the management for maximum diagnostic and patient benefit. PMID- 11782087 TI - Institutional review of outside cytology materials: a retrospective analysis of two institutions' experiences. AB - Discrepancy rates between original and review histopathologic diagnoses have been well-studied, and range as high as 30% in some studies. While the sensitivity and specificity rates for a variety of cytologic specimens are well-known, few data exist as to the discrepancy rates associated with in-house, second-opinion reviews of outside material. We studied the 2-yr experience of two university based medical centers' reviews of outside cytology materials. A total of 146 cases underwent second-opinion review. The majority were fine-needle aspiration specimens obtained from the breast, thyroid, lung, and hematobiliary system. Nine cases were cervical vaginal specimens, 19 were bronchial brushes, washings, or lavage specimens, 13 were pleural fluid specimens, 5 were bile duct brushings, and the remainder were exfoliative cytologies, including those from the cerebrospinal fluid, urine, and pelvis. In all, 24 disagreements were encountered, 11 of which were considered major in that a significant change in therapy occurred due to an alteration in diagnosis, while 13 were considered minor in that a different diagnosis or subclassification was given by the consultant pathologist, but this diagnostic change did not significantly alter therapy. The overall diagnosis disagreement rate of 16% is similar to the diagnostic discrepancy rate encountered in second-opinion reviews of surgical pathology specimens. The 8% major discrepancy rate is slightly higher than that seen in similar studies of surgical pathology material. PMID- 11782089 TI - Endocervical component: is it a determinant of specimen adequacy? AB - There is controversy in the literature concerning the presence or absence of an endocervical component as a determinant of the adequacy of cervical cellular samples. The purpose of this retrospective 2-yr study (January 1, 1999-December 31, 2000) was to evaluate the diagnostic accuracy of ThinPrep Pap Tests with the presence or absence of an endocervical component from 151 women with subsequent tissue-verified cervical intraepithelial neoplasia (CIN) II/III. Of the 138 Pap Tests containing an endocervical component, 100 (73%) showed exact cyto/histologic correlation and 38 (27%) were discordant. Of the 13 Pap Tests lacking an endocervical component, 10 (77%) showed exact correlation and 3 (23%) were discordant. Statistical analysis showed no significant difference in the detection of a high-grade squamous intraepithelial lesion (HSIL) in those ThinPreps that contained an endocervical component from those that did not (P > 0.5). Further analysis of the 41 discordant ThinPrep Pap Tests showed no significant difference between negative Pap Tests and discordant, yet abnormal Pap Tests (atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesions) and the presence or absence of an endocervical component (P = 0.25). The results of this study seem to indicate that the issue of the lack of an endocervical component as a determinant of cervical specimen adequacy should be revisited. PMID- 11782090 TI - Usefulness of Auto Cyto Fix (membrane filter method) for the application of immunohistochemistry. AB - We developed the Auto Cyto Fix (ACF) 1000 as an experimental model, which was adapted as a membrane filter method for automatically making smear preparations fixed with 95% ethanol. In this study, immunohistochemistry was applied to the cells smeared on the membrane filter, and effectiveness was examined. Twenty-four effusions and HeLa 229 cells were used. These cell samples were produced by the ACF1000 on the membrane filter and stained by the Papanicolaou method. After observation, these were decolored and stained by immunohistochemical techniques. Antibodies included CEA, EMA, and MIB-1. CEA and EMA were detected by the indirect method, and were colored by DAB, AEC, and new fuchsin. MIB-1 was detected by the immunoperoxidase (LSAB) and the immunofluorescence method. A uniformly stabilized immunoreaction was obtained and was equivalent to or better than that of the conventional technique. In addition, there was no background staining on the membrane filter. Based on these results, the membrane filter preparation produced by the ACF1000 was also effectively applied to immunohistochemical observations. PMID- 11782091 TI - Comparison of three commonly used cytologic preparations in effusion immunocytochemistry. AB - Discrepant results in effusion immunocytochemistry are often the result of specimen processing. Smears, cytospins, cell blocks, and monolayer preparations have all been used in various published studies; thus, there is no consistency in the immunostaining process for cytology to compare with the surgical pathology "gold standard" results. We sought to evaluate optimal specimen preparation for the immunostaining of effusion samples. Fourteen reactive and 15 malignant effusion samples (various epithelial/mesothelial neoplasms) were each prepared in three forms: air-dried cytospins (postfixed in ethanol), formalin-fixed, paraffin embedded cell blocks, and liquid-based thin-layer (ThinPrep, CYTYC, Boxborough, MA) processing. All slides were immunostained with antibodies commonly used in effusion cytology: HBME-1, calretinin, E-cadherin, BerEP4, B72.3, LeuM1, and CA19 9. Cytospin and ThinPrep samples performed in a similar manner: high background staining was encountered in 66% of cases, most evident in three-dimensional clusters of cells. In addition, membrane staining patterns were difficult to interpret. Cell blocks provided the best milieu for morphologic interpretation, with less background staining (only 17% of cases) and results that most closely approximated those reported in the surgical pathology literature. The cost per test for cell block immunocytochemistry was also the most economical for our laboratory. PMID- 11782092 TI - Pathogenesis of nodular histiocytic hyperplasia in serous effusions. PMID- 11782093 TI - Abortion, distant peoples, and future generations. PMID- 11782094 TI - Why abortion is immoral. PMID- 11782095 TI - Sensationalized philosophy: a reply to Marquis's "Why abortion is immoral. PMID- 11782096 TI - Does a fetus already have a future-like-ours? PMID- 11782097 TI - Killing, abortion, and contraception: a reply to Marquis. PMID- 11782098 TI - Abortion and simple consciousness. PMID- 11782101 TI - In vitro cytokine secretion in individuals with schizophrenia: results, confounding factors, and implications for further research. AB - The present paper reviews the results of all publications on in vitro cytokine secretion in patients with schizophrenia, as published by March 2001. The authors supply easy to read tables with respect to the individual cytokines and soluble cytokine receptors investigated, the in vitro methodology used, characterization of the patient samples, and the results on cytokine secretion as stated in these studies. Inconsistent results, e.g., regarding in vitro secretion of IL-2 with 11/18 studies finding decreased secretion, 5/18 finding no change, and 2/18 finding increases, cannot systematically be correlated with any methodological procedures nor any diagnostic subtypes, per se. However, factors such as medication and cigarette smoking are likely to play a role. The authors suggest that more hypothesis-driven research, together with more carefully designed studies, as well as better communication between basic or animal researchers and clinicians might help to answer the question of whether there are meaningful peripheral changes in the immune system related to schizophrenia. PMID- 11782102 TI - Review of immunological and immunopathological findings in schizophrenia. AB - The involvement of immunological and immunopathological mechanisms in the etiopathogenesis of schizophrenia has been a matter of research, with recently increasing effort. This article reviews the findings focusing on postmortem neuropathology, the blood-brain barrier, antibodies, acute phase proteins, immunocompetent cells, and activation markers of immunocompetent cells. Evidence for the two primarily postulated hypotheses (the infectious hypothesis and the autoimmune hypothesis) is critically discussed. On the basis of the findings, perspectives for future research are outlined aiming at a precise and consequent strategy to elucidate a potential involvement of immune mechanisms in the etiopathogenesis of schizophrenia. PMID- 11782103 TI - T-helper-1 and T-helper-2 responses in psychiatric disorders. AB - The expanding field of psychoneuroimmunology has markedly increased knowledge about the interference of the central nervous system and the immune system. Immunological abnormalities in psychiatric patients have been repeatedly described in the last century. Modern concepts of immunology and the growing knowledge of psychoneuroimmunology may help in understanding the distinct immunological mechanisms in psychiatric disorders. One of these concepts regarding the adaptive immune system is the discrimination between Th1-like cell mediated and Th2-like antibody-related immune responses. This article systematically describes alterations of Th1- or Th2-specific parameters in the major psychiatric disorders schizophrenia, major depression, and Alzheimer's disease. There are several hints of associations of these two distinct arms of immune response with subgroups of schizophrenia and major depression. The immunological research in Alzheimer's disease has already led to a preclinical model of immunotherapy. Categorization of immune parameters may also help to identify a possible immune-related pathophysiology in psychotic and affective disorders, resulting in specific treatment strategies. PMID- 11782104 TI - Behavioral effects of cytokines. PMID- 11782105 TI - Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. AB - Increasingly, abnormalities of glial cell function have been implicated in pathological studies of the major mental illnesses (schizophrenia, bipolar disorder, and major depression). In a recent proteomic study, four isoforms of astrocytic glial fibrillary acidic protein (GFAP) were decreased in one or more of these diseases. In the current study, we sought to determine the immunohistochemical localization of phosphorylated GFAP (pGFAP) in the prefrontal cortex and hippocampus and to describe possible disease-related changes in the distribution of pGFAP containing astrocytes. In the prefrontal cortex, interlaminar astrocytes in layer I and stellate astrocytes in layers II and VI were labeled. Labeled cells were also present adjacent to blood vessels in the gyral white matter and in underlying white matter generally. In the hippocampus, labeled cells were present in the polymorphic layer of the dentate gyrus. In the prefrontal cortex, schizophrenia and major depression were characterized by decreased labeling of astrocytes adjacent to blood vessels. There were no significant differences between the diagnostic groups in the other prefrontal layers or in the hippocampus. These results suggest that reduced numbers or functional regulation of pGFAP containing astrocytes occurs in schizophrenia and major depression. The mechanism by which this deficit occurs is not known, but it may adversely effect the regulation of neuronal metabolism, communication, and response to injury. PMID- 11782106 TI - The schizophrenia-rheumatoid arthritis connection: infectious, immune, or both? AB - Schizophrenia and rheumatoid arthritis share an impressive number of similarities. Both are chronic, relapsing diseases of unknown etiology. Both became prominent in the early 19th century and have prevalences of approximately 1% in North America and Europe. Both run in families, have pairwise concordance rates of approximately 30% among monozygotic twins, and are more common among individuals born in urban areas. For both diseases, studies have reported greater exposure to cats in childhood than in controls. Both diseases have been associated with similar class II HLA antigens. Both have also been suspected of having infectious etiology, with similar agents--retroviruses, herpesviruses including EBV, and Toxoplasma gondii--having been associated in some cases. Since there is also a well-documented inverse correlation between these two diseases, it is possible that they share a common infectious and/or immune etiology and that once a person gets one of the diseases then they are relatively immune to the other. PMID- 11782107 TI - Maternal cytokine levels during pregnancy and adult psychosis. AB - We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1-beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t = 2.22, p =.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6, or IL 8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring. PMID- 11782108 TI - New human teeth from Middle Stone Age deposits at Klasies River, South Africa. AB - Since 1984, the main site at Klasies River has been re-investigated. Human remains, animal bones and stone artefacts have been collected from the LBS, SAS and other stratigraphic members, and these discoveries help to establish the antiquity of anatomically near-modern populations practicing a Middle Stone Age way of life on the southern coast of Africa. Several teeth found in the lower SAS levels in 1989-1991 can be matched in recent South African populations. Two complete upper molars representing one individual have crowns that are relatively short mesiodistally. These specimens are small in comparison to black South African homologues, but MD and BL dimensions fall close to the averages for San burials. This evidence confirms that several of the Klasies individuals have very small molars, while others have cheek teeth that are close to the upper limits for size variation in recent Africans. The new material is in keeping with the view that sex dimorphism within this Middle Stone Age population may be pronounced. PMID- 11782109 TI - Adaptive and phylogenetic significance of ontogenetic sequences in Archaeolemur, subfossil lemur from Madagascar. AB - Among the best known of recently extinct Malagasy lemurs is Archaeolemur, which is represented by many hundreds of specimens. The phylogenetic affinities of this taxon are unclear, especially in light of recent preliminary analysis of ancient DNA which does not support its previously accepted close relationship with the living Indridae. We examined the nearly complete skeletons of two adults and one juvenile and other less complete specimens to reconstruct aspects of the ontogeny of Archaeolemur. To compare the development of Archaeolemur to that of living strepsirrhines we collected data on Propithecus verreauxi, Eulemur fulvus, and Lemur catta. Additionally, because Archaeolemur exhibits some morphological convergences with distantly related papionins, we tested for convergence in the developmental patterns of Archaeolemur and Macaca fascicularis. Data include the status of tooth eruption, craniofacial sutural closure, and postcranial epiphyseal fusion, as well as linear measurements. We used discriminant function analysis and other tools to explore ontogenetic similarities and differences. The adaptive and phylogenetic significance of ontogenetic information is discussed. Our analysis shows that Archaeolemur displays a clear strepsirrhine pattern of development with only minor macaque convergences. Among the Strepsirrhini, Archaeolemur is slightly more similar developmentally to E. fulvus and L. catta than to P. verreauxi. Some of the distinctive features of the ontogeny of Archaeolemur may be related to diet, while others bear apparent testimony to a relatively rapid absolute pace of growth and development. PMID- 11782110 TI - Astragalar morphology of late Eocene anthropoids from the Fayum Depression (Egypt) and the origin of catarrhine primates. AB - The phylogenetic relationships of the late Eocene anthropoids Catopithecus browni and Proteopithecus sylviae are currently a matter of debate, with opinion divided as to whether these taxa are stem or crown anthropoids. The phylogenetic position of Catopithecus is of particular interest, for, unlike the highly generalized genus Proteopithecus, this taxon shares apomorphic dental and postcranial features with more derived undoubted catarrhines that appear in the same region 1 2 Ma later. If these apomorphies are homologous and Catopithecus is a stem catarrhine, the unique combination of plesiomorphic and apomorphic features preserved in this anthropoid would have important implications for our understanding of the crown anthropoid morphotype and the pattern of morphological character transformations that occurred during the early phases of stem catarrhine evolution.Well-preserved astragali referrable to Proteopithecus, Catopithecus, and the undoubted early Oligocene stem catarrhine Aegyptopithecus have provided additional morphological evidence that allows us to further evaluate competing hypotheses of interrelationships among Eocene-Oligocene Afro Arabian anthropoids. Qualitative observations and multivariate morphometric analyses reveal that the astragalar morphology of Proteopithecus is very similar to that of early Oligocene parapithecids and living and extinct small-bodied platyrrhines, and strengthens the hypothesis that the morphological pattern shared by these taxa is primitive within crown Anthropoidea. In contrast, Catopithecus departs markedly from the predicted crown anthropoid astragalar morphotype and shares a number of apomorphic features (e.g., deep cotylar fossa, laterally projecting fibular facet, trochlear asymmetry, mediolaterally wide astragalar head) with Aegyptopithecus and Miocene-Recent catarrhines. The evidence from the astragalus complements other independent data from the dentition, humerus and femur of Catopithecus that support this taxon's stem catarrhine status, and we continue to maintain that oligopithecines are stem catarrhines that constitute the sister group of a clade containing propliopithecines and Miocene-Recent catarrhines. PMID- 11782111 TI - Recently identified postcranial remains of Paranthropus and early Homo from Swartkrans Cave, South Africa. AB - Fifteen newly recognized hominid postcranials from Swartkrans are described here and compared with a sample of previously described early hominids, African apes and modern humans. Ten of the new specimens are from Member 1. Two are from Member 2 and three are from Member 3. Nine of the fossils are referred to Paranthropus, three to Homo, and three specimens cannot be assigned at present. The collection of hominid postcranials from Members 1-3 at Swartkrans now numbers more than 70 specimens. With the description of two new, small femoral heads, SKW 19 and SK 3121, there are now four proximal femora from Swartkrans. When SK 82 and SK 97 are compared with SKW 19 and SK 3121, the two sets offer important insights into body size and sexual dimorphism in Paranthropus robustus.A new distal femur, SK 1896 and other bones attributed to Homo cf. erectus, indicate that male Homo were larger than Paranthropus at Swartkrans. PMID- 11782112 TI - An early bone tool industry from the Middle Stone Age at Blombos Cave, South Africa: implications for the origins of modern human behaviour, symbolism and language. AB - Twenty-eight bone tools were recovered in situ from ca. 70 ka year old Middle Stone Age levels at Blombos Cave between 1992 and 2000. These tools are securely provenienced and are the largest collection to come from a single African Middle Stone Age site. Detailed analyses show that tool production methods follow a sequence of deliberate technical choices starting with blank production, the use of various shaping methods and the final finishing of the artefact to produce "awls" and "projectile points". Tool production processes in the Middle Stone Age at Blombos Cave conform to generally accepted descriptions of "formal" techniques of bone tool manufacture. Comparisons with similar bone tools from the Later Stone Age at Blombos Cave, other Cape sites and ethnographic collections show that although shaping methods are different, the planning and execution of bone tool manufacture in the Middle Stone Age is consistent with that in the late Holocene. The bone tool collection from Blombos Cave is remarkable because bone tools are rarely found in African Middle or Later Stone Age sites before ca. 25 ka. Scarcity of early bone tools is cited as one strand of evidence supporting models for nonmodern behaviour linked to a lack of modern technological or cognitive capacity before ca. 50 ka. Bone artefacts are a regular feature in European sites after ca. 40 ka, are closely associated with the arrival of anatomically modern humans and are a key behavioural marker of the Upper Palaeolithic "symbolic explosion" linked to the evolution of modern behaviour. Taken together with recent finds from Klasies River, Katanda and other African Middle Stone Age sites the Blombos Cave evidence for formal bone working, deliberate engraving on ochre, production of finely made bifacial points and sophisticated subsistence strategies is turning the tide in favour of models positing behavioural modernity in Africa at a time far earlier than previously accepted. PMID- 11782113 TI - High-precision U-series dating of Locality 1 at Zhoukoudian, China. AB - Thermal ionization mass spectrometric(230)Th/(234)U dating has been carried out on intercalated speleothem samples from the limestone cave occupied by Homo erectus at Zhoukoudian, China. The samples were recently collected in proper stratigraphic context after detailed field examinations. The results show that the age of the No. 5 Skull from Layer 3 is >400 ka, possibly in the range of about 400-500 ka, and that the hominid fossils from the lower strata are at least 600 ka and possibly >800 ka, much older than previously thought. The near equilibrium(230)Th/(234)U ratios and internal consistency of the dates and stratigraphy lend credence to the results and allow us to comment on their important implications for human evolution. PMID- 11782114 TI - A new cranium of Dryopithecus from Rudabanya, Hungary. PMID- 11782116 TI - Outer membrane-like vesicles secreted by Actinobacillus actinomycetemcomitans are enriched in leukotoxin. AB - Actinobacillus actinomycetemcomitans is associated with early onset periodontal diseases and secretes membranous vesicles that appear to contain several virulence-associated proteins. However, the composition of these vesicles and the process leading to their secretion are not well defined. Electron micrographs of thin sectioned bacterial cells and purified vesicle preparations showed that vesicles are spherical lipid bilayers, 50-100 nm in diameter, that appear to form by budding from the outer membrane of the bacterium. Thin layer chromatography identified the predominant lipid components of vesicles as lipopolysaccharide, phosphatidylethanolamine and cardiolipin, similar to the main lipid constituents of the outer membrane. However, vesicles also contained minor lipids that were not detected in outer membrane samples. The major protein constituents of vesicles co-migrated with proteins in outer membrane extracts of A. actinomycetemcomitans, but the outer membrane preparations possessed polypeptides that were not detected in vesicles. Three vesicle proteins were identified; the heat-modifiable OmpA homologue of A. actinomycetemcomitans, a 28 kDa lipoprotein related to the major outer membrane lipoprotein of Mannheimia haemolytica and leukotoxin. Incubation of leukotoxin-sensitive human HL60 cells with vesicles from A. actinomycetemcomitans strains JP2 and 652 resulted in cell lysis, indicating that vesicle-associated leukotoxin is biologically active. Vesicles from the highly leukotoxic strain JP2 were five- to 10-fold more toxic than vesicles from the minimally leukotoxic 652 strain. Furthermore, the specific leukotoxic activity of JP2 vesicles was approximately four- to five-fold higher than isolated outer membrane preparations from JP2, suggesting that vesicles are enriched in leukotoxin. Together, these results suggest that the formation of A. actinomycetemcomitans vesicles occurs by a process that results in the enrichment of leukotoxin. PMID- 11782117 TI - Excess production of interleukin-12 subunit p40 stimulated by the virulence plasmid of Salmonella enterica serovar Typhimurium in the early phase of infection in the mouse. AB - The production of interleukin-12 (IL-12) and its subunits in response to Salmonella enterica serovar Typhimurium infection in the BALB/c mouse was examined. Unlike wild-type Typhimurium, a plasmidless strain, isolated by curing of the virulence plasmid (pSTV), did not stimulate excess IL-12p40 production. When a Tn 5 tagged pSTV was transferred back to the plasmidless strain, the ability to stimulate IL-12p40 production was restored. However, a strain harbouring another Tn50pSTV failed to stimulate excess IL-12p40 production. This Tn 5 insertion area, located on fragment H3 of pSTV, was designated spf (stimulation of protein forty). The ability to stimulate IL-12p40 production was restored in a partial diploid that carried a wild-type fragment covering the spf site. There is one known gene, repA, a locus, rsk, and two putative ORFs, in the vicinity of the Tn 5 insertion site; however, these are not spf. The precise location of the spf locus is still unknown. PMID- 11782118 TI - Pseudomonas aeruginosa-induced lung injury: role of oxidative stress. AB - Pseudomonas aeruginosa is a Gram-negative pathogen that can cause lung injury in immunocompromised patients, primarily by inducing a release of host-derived mediators responsible for the influx of phagocytes to the lung. These phagocytes exert their antimicrobial actions by releasing toxic metabolites, including reactive oxygen species and proteases, which can also cause cell injury. This study was carried out to assess the pulmonary oxidant-antioxidant status of male adult Sprague-Dawley rats infected with different numbers of P. aeruginosa (10(4) 10(7)cfu/animal). Intratracheal instillation of P. aeruginosa resulted in lung injury, as evidenced by increases in wet lung weight and decreases in the lung activities of angiotensin converting enzyme and alkaline phosphatase, enzymes localized primarily in pulmonary endothelial and alveolar type II epithelial cells, respectively. The P. aeruginosa -induced lung injury was directly related to the infiltration of neutrophils, as indicated by increases in myeloperoxidase activity. The challenge of animals with P. aeruginosa resulted in increases in lipid peroxidation and decreases in glutathione content, which were associated with the indices of lung injury and neutrophil infiltration. Such a challenge also resulted in weakening the antioxidant defence system, as evidenced by decreases in superoxide dismutase, catalase and glutathione peroxidase activities. These data suggest that changes in the pulmonary oxidant-antioxidant status may play an important role in the P. aeruginosa -induced lung injury. PMID- 11782119 TI - Increased frequency of intestinal Escherichia coli carrying genes for S fimbriae and haemolysin in IgA-deficient individuals. AB - Persons with selective IgA deficiency carry an increased risk of coeliac disease, inflammatory bowel disease and perhaps also gastrointestinal malignancies. Inflammatory bowel disease is associated with an increased carriage of adherent and haemolytic Escherichia coli in the intestinal microflora. This study was designed to investigate whether IgA-deficient individuals carry E. coli with virulence-associated properties in their gut flora. The last free-lying colony of E. coli isolates obtained from rectal flora of 25 IgA-deficient and 20 age matched control individuals was assayed by multiplex PCR for genes for the following adhesins or virulence determinants: P, type 1 and S fimbriae, Dr haemagglutinin, haemolysin, aerobactin and the capsular types K1 and K5. E. coli strains from the intestinal microflora of IgA-deficient individuals more often had the gene for S fimbriae (36% of the strains compared with 0% in control subjects, P=0.003) as well as for haemolysin (40 vs 10% of the strains, P=0.040). IgA-deficient individuals had instead lower frequencies of E. coli carrying genes for type 1 fimbriae in their microflora (68 vs 90%, P=0.14). The results suggest that IgA-deficient individuals carry an increased frequency of E. coli with potentially inflammatogenic properties in their microflora, which may contribute to the development of gastrointestinal disorders such as inflammatory bowel diseases. PMID- 11782120 TI - Mannose-receptor positive and negative mouse macrophages differ in their susceptibility to infection by Chlamydia species. AB - It has been shown that N-linked high mannose type oligosaccharides competitively inhibits attachment to and infectivity of chlamydiae in HeLa cells. To further study whether mannose moieties are involved in the infectivity of chlamydiae, the susceptibility of mannose-receptor negative J774A and positive J774E mouse macrophages to Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae was evaluated. C. trachomatis infected mannose-receptor positive cells better than mannose-receptor negative cells. C. psittaci infected both mannose-receptor negative and positive cells equally well, while C. pneumoniae infected mannose receptor negative cells better than mannose-receptor positive cells. Further studies using this system may provide insight into the role of mannose-receptor in attachment, entry and survival of chlamydiae in macrophages. PMID- 11782121 TI - Reactive oxygen species as mediators in asthma. AB - This review describes production and effects of reactive oxygen species (ROS) on airway function. ROS are important in many physiological processes but can also have detrimental effects on airway cells and tissues when produced in high quantities or during the absence of sufficient amounts of anti-oxidants. Therefore, these mediators play a prominent role in the pathogenesis of various inflammatory airway disorders, including asthma. Effects of ROS on airway function in asthma have been studied with isolated airway cells and tissues and with animal models and patients. With the use of inhibitors, transgenic animals and measurements of the release of ROS within the airways, it became clear that oxidative stress contributes to the initiation and worsening of inflammatory respiratory disorders. PMID- 11782122 TI - The Non-neuronal cholinergic system: an emerging drug target in the airways. AB - The non-neuronal cholinergic system is widely expressed in human airways. Choline acetyltransferase (ChAT) and/or acetylcholine are demonstrated in more or less all epithelial surface cells (goblet cells, ciliated cells, basal cells), submucosal glands and airway smooth muscle fibres. Acetylcholine is also demonstrated in the effector cells of the immune system (lymphocytes, macrophages, mast cells). Epithelial, endothelial and immune cells express nicotinic and muscarinic receptors. Thus the cytomolecule acetylcholine can contribute to the regulation of basic cell functions via auto-/paracrine mechanisms (proliferation, differentiation, ciliary activity, secretion of water, ions and mucus, organization of the cytoskeleton, cell-cell contact). Acetylcholine also modulates immune functions (release of cytokines; proliferation, activation and inhibition of immune cells). Preliminary experimental evidence suggests that mucosal inflammation may be associated with raised acetylcholine levels, impairing cell and organ homeostasis. It should be considered that anti-muscarinic drugs which are applied for the treatment of chronic airway diseases antagonize the effect of both neuronal and non-neuronal acetylcholine. Non-neuronal acetylcholine, however, is still active, possibly directly within the cell cytosol and also via nicotinic receptors localized on various non-neuronal cells. It is an essential task to clarify the pathophysiological role of the non-neuronal cholinergic system in more detail to develop new drugs which can target the synthesis, release, inactivation and cellular activity of non-neuronal acetylcholine. PMID- 11782123 TI - The development and evaluation of a new aerosol irritant assay with minimal animal stress. AB - Current aerosol irritant assays trap animals in noxious atmospheres and put a lot of stress on them. For this reason, the Minimal Animal Stress Irritant Assay Chamber (MASIAC) was developed based on the principle of avoidance, and evaluated. The MASIAC reproducibly detected citric acid with more sensitivity than conventionally used assays. With a group of mice tested simultaneously, the responses were not significantly affected by the presence of other mice. In addition, following multiple exposures to citric acid, the mice either sensitized to the irritant, or learned to avoid it. This suggests a number of areas where the MASIAC could be applied, including behavioral and asthma research. If this new method turns out to be as good as currently used assays, it could provide investigators with an alternative, more humane method of evaluating pulmonary irritants. PMID- 11782124 TI - Auxotonic contractile responses of rat tracheal and bronchial airway smooth muscle. AB - The purposes of the present study were to directly compare: (1) the degree of trachealis muscle shortening and changes in tracheal dimensions and (2) ACh mediated auxotonic contraction of trachea and intraparenchymal bronchi. The auxotonic contractile properties of tracheal and bronchial airway smooth muscle were assessed from 1-2 mm thick tracheal sections and;1 mm thick lung slices using videomicrometry in vitro at 37 degrees C. Acetylcholine resulted in reductions in luminal area, perimeter, mean radius, length, and breadth (22.0, 10.0, 11.9, 10.7 and 12.0%, respectively). Trachealis muscle shortening reached a maximum of 39.8+/-4.3%. The K(+)channel blocker 4-aminopyridine significantly augmented the ACh-mediated reductions in tracheal luminal dimensions. In response to ACh (10(-3)m), reductions in bronchial dimensions were significantly greater than those of the trachea for luminal area, perimeter and mean radius (44.6 vs. 18.6, 32.0 vs. 8.0 and 28.9 vs. 9.9%, respectively). These data indicate that auxotonic contractile responses of rat tracheal smooth muscle differ from those previously reported in the dog and guinea pig, that ACh-mediated auxotonic contraction of tracheal smooth muscle is augmented by 4-aminopyridine, and that proportionate reductions in luminal dimensions in response to ACh are considerably greater for bronchial than tracheal airways. PMID- 11782125 TI - Respiratory effects of halothane in a patient with refractory status asthmaticus. AB - We describe the case of a 36 year old patient who was admitted to the intensive care unit (ICU) for an acute asthma attack that failed to respond to conventional treatment and required mechanical ventilation. The patient's condition improved after halothane was administered; treatment with this inhalational anaesthetic lasted 7 h, and the beneficial effect was obtained by employing concentrations between 0.5 and 2%. Under constant mechanical ventilator settings, a highly significant linear correlation between peak airway pressure and arterial pCO(2)(r: 0.98 P<0.001) was observed. The decrease in p(a)CO(2)induced by halothane may be explained by the diminished dead space that results from the drop in peak airway pressure. Arterial hypotension, which improved with inotropic agents, was the only complication that seemed related to the inhaled anaesthetic. The patient was extubated 24 h after her arrival to the ICU and discharged 72 h later. A causal relationship between the administration of halothane and clinical improvement is suggested. PMID- 11782126 TI - Inhalation of alpha(1)-protease inhibitor in cystic fibrosis does not affect surfactant convertase and surface activity. AB - The inhalation of alpha(1)-protease inhibitor (alpha(1)-PI) was assessed in a pilot study to restore the protease-antiprotease balance in the lungs of cystic fibrosis (CF) patients. In addition, the effect of this treatment on the surface active properties of lung surfactant and the metabolic conversion of aggregate forms was studied. Eight young adults with CF inhaled 100 mg of alpha(1)-PI twice daily over 8 weeks and bronchoalveolar lavages (BAL) were obtained before and 12 h after the last inhalation. Large aggregate (LA) forms of surfactant were isolated from the in vivo material by ultracentrifugation and their conversion into small aggregates (SA) was assessed by an in vitro surface area cycling assay. Although alpha(1)-PI partially restored the protease-anti-protease imbalance and reduced BAL protein content, no effects were noted on the impaired minimal surface tension and on the in vivo and in vitro conversion of LA to SA. Antiserum against the specific carboxyl esterase ES-2, previously identified in mice and rats as the putative surfactant convertase, did not detect a protein of the appropriate size in CF BAL. Whereas short-term inhalation of alpha(1)-PI was beneficial for the proteolytic aspects of CF lung injury, this appeared not to be the case for surfactant conversion and surface activity. PMID- 11782127 TI - Enzyme-like catalysis by molecularly imprinted polymers. PMID- 11782128 TI - The chemistry of azetidin-3-ones, oxetan-3-ones, and thietan-3-ones. PMID- 11782129 TI - Solid phase heterocyclic chemistry. PMID- 11782130 TI - Electronic requirements for macropolyhedral boranes. PMID- 11782131 TI - High oxidation state multiple metal-carbon bonds. PMID- 11782132 TI - Multiply charged anions in the gas phase. PMID- 11782133 TI - Synthesis and properties of phosphetanes. PMID- 11782134 TI - Atomic and molecular electron affinities: photoelectron experiments and theoretical computations. PMID- 11782136 TI - New crown-shaped polyoxovanadium(V) cluster cation with a mu(6)-sulfato anion and zwitterionic mu-(beta-alanine): crystal structure of [V(6)O(12)(OH)(3)(O(2)CCH(2)CH(2)NH(3))(3)(SO(4))][Na][SO(4)].13H(2)O. AB - Treatment of vanadium(V) oxide with an ethanol-concentrated sulfuric acid mixture, followed by the addition of an equimolar amount of beta-alanine and sodium hydroxide, and finally raising the pH to 3.9 with sodium carbonate solution, under continuous heating in a water bath and in the presence of air, leads to the polyionic sodium cyclo-[mu(6)-(sulfato-O,O',O'')tris[mu-(beta alanine-O,O')-mu-oxo]tris(mu-hydroxo-mu-oxo)hexa[oxovanadium(V)]] sulfate tridecahydrate which crystallizes in the monoclinic P2(1)/n space group [a = 9.5192(4), b = 20.1185(9), c = 22.6174(9) A, beta = 97.011(1) degrees; Z = 4]. The crown-shaped polyoxovanadium(V) cluster cation, with carboxylate-bridging amino acid ligands, has an Anderson structure with two unique capping sulfato ligands. Its structural analysis, together with IR, UV-vis, and preliminary data on its solution properties, is presented. PMID- 11782138 TI - Photochemistry of trimethyltin iodide in polar media: orbital parentage and observed reactivity. AB - (CH(3))(3)SnI exists as individual tetrahedral molecules in hexane but reacts with the silanol moieties present on the surface of porous glass and with the hydroxyl group of ethanol and hexanol to form five-coordinate adducts. With the exception of slight shifts to higher energy, formation of the adduct has little effect on the electronic spectrum of the complex, and the wavelength and O(2) dependencies of the quantum yield of (CH(3))(3)SnI disappearance indicate that the photochemistry of the complex initiates from the ligand-to-metal charge transfer (LMCT) state populated on absorption in each medium. Nevertheless, 254 nm excitation in hexane leads to I(2) and ((CH(3))(3)Sn)(2), whereas excitation of the five-coordinate adduct on the glass surface leads to I(2), I(3)(-), ((CH(3))(3)Sn)(2), and (CH(3))(3)Sn-OSi[triple bond](OSi[triple bond]represents a surface siloxyl), while in ethanol, I(3)(-) is the only detectable product. Regardless of the medium, the ground state is polarized and population of the LMCT state creates a more uniform charge distribution from which homolytic cleavage of the (CH(3))(3)Sn-I bond is the dominant reaction pathway in each medium. In hexane, the (CH(3))(3)Sn(*) and I(*) radicals couple to form ((CH(3))(3)Sn)(2) and I(2), whereas adsorbed onto the glass, a fraction of the radical pairs thermalize via electron transfer to form I(3)(-) and a surface bound (CH(3))(3)Sn-OSi[triple bond] species. In ethanol, excitation of the solvent adduct (CH(3))(3)Sn-OHC(2)H(5) leads to homolytic cleavage and I(2) formation, which reacts thermally with (CH(3))(3)Sn-OHC(2)H(5) to form an [(CH(3))(3)Sn(+), I(3)(-)] ion pair. PMID- 11782137 TI - Kinetics, mechanism, and spectroscopy of the reversible binding of nitric oxide to aquated iron(II). An undergraduate text book reaction revisited. AB - A detailed kinetic and mechanistic analysis of the classical "brown-ring" reaction of [Fe(H(2)O)(6)](2+) with NO was performed using stopped-flow and laser flash photolysis techniques at ambient and high pressure. The kinetic parameters for the "on" and "off" reactions at 25 degrees C were found to be k(on) = 1.42 x 10(6) M(-1) s(-1), DeltaH(++)(on) = 37.1 +/- 0.5 kJ mol(-1), DeltaS(++)(on) = -3 +/- 2 J K(-1) mol(-1), DeltaV(++)(on) = +6.1 +/- 0.4 cm(3) mol(-1), and k(off) = 3240 +/- 750 s(-1), DeltaH(++)(off) = 48.4 +/- 1.4 kJ mol(-1), DeltaS(++)(off) = 15 +/- 5 J K(-1) mol(-1), DeltaV(++)(off) = +1.3 +/- 0.2 cm(3) mol(-1). These parameters suggest that both reactions follow an interchange dissociative (I(d)) ligand substitution mechanism, which correlates well with the suggested mechanism for the water exchange reaction on [Fe(H(2)O)(6)](2+). In addition, Mossbauer spectroscopy and EPR measurements were performed on the reaction product [Fe(H(2)O)(5)(NO)](2+). The Mossbauer and EPR parameters closely resemble those of the [FeNO](7) units in any of the other well-characterized nitrosyl complexes. It is concluded that its electronic structure is best described by the presence of high-spin Fe(III) antiferromagnetically coupled to NO(-) (S = 1) yielding the observed spin quartet ground state (S = (3)/(2)), i.e., [Fe(III)(H(2)O)(5)(NO( ))](2+), and not [Fe(I)(H(2)O)(5)(NO(+))](2+) as usually quoted in undergraduate text books. PMID- 11782139 TI - Syntheses and solid state structures of tris(pyrazolyl)methane complexes of sodium, potassium, calcium, and strontium: comparison of structures with analogous complexes of lead(II). AB - The reaction of NaI with 2 equiv of HC(pz)(3) or HC(3,5-Me(2)pz)(3) (pz = pyrazolyl ring) leads to the formation of [[HC(pz)(3)](2)Na](I) (1) and [[HC(3,5 Me(2)pz)(3)](2)Na](I) (2), respectively. Both compounds have trigonally distorted octahedral arrangements about the sodium. A similar reaction of KPF(6) with HC(3,5-Me(2)pz)(3) results in the formation of [[HC(3,5-Me(2)pz)(3)](2)K](PF(6)) (3), a complex also shown crystallographically to have a trigonally distorted octahedral arrangement about the potassium, which is an unusually low coordination number for this large metal ion. The complex [[HC(pz)(3)](2)Sr](BF(4))(2) (4) forms in the reaction of Sr(acac)(2) (acac = acetylacetonate) with HBF(4).Et(2)O followed by 2 equiv of HC(pz)(3). The structure is highly distorted, showing kappa(3) bonding of both tris(pyrazolyl)methane ligands and, in addition, interactions with the metal from three fluorine atoms from the BF(4)(-) counterions. The symmetrical structure of 1 and the nine-coordinate structure of 4 are both very different from the distorted, six-coordinate structure [[HC(pz)(3)](2)Pb](BF(4))(2), indicating that for this compound the lone pair on lead(II) is influencing the structure. The reaction of M(acac)(2) (M = Sr, Ca) with H[B[3,5-(CF(3))(2)C(6)H(3)](4)] followed by 2 equiv of HC(pz)(3) produces [[HC(pz)(3)](2)(Hacac)Sr][B[3,5 (CF(3))(2)C(6)H(3)](4)](2) (5) (when the reaction is done in CH(2)Cl(2)), [[HC(pz)(3)](2)(Me(2)CO)(2)Sr][B[3,5-(CF(3))(2)C(6)H(3)](4)](2) (6) (when the reaction is done in acetone), and [[HC(pz)(3)](2)(Hacac)Ca][B[3,5 (CF(3))(2)C(6)H(3)](4)](2)(7), respectively. The structures of all three complexes show a distorted eight-coordinate arrangement of the ligands about the metal. Crystal data: 1 is orthorhombic, Pnma, a = 16.931(1), b = 22.368(3), c = 7.937(2) A, alpha = 90, beta = 90, gamma = 90 degrees, Z = 4; 2 is trigonal, R3, a = 10.7483(8), b = 10.7483(8), c = 35.395(4) A, alpha = 90, beta = 90, gamma = 120 degrees, Z = 3; 3 is monoclinic, P2(1)/c, a = 9.144(4), b = 13.377(6), c = 15.988(7) A, alpha = 90, beta = 92.291(10), gamma = 90 degrees, Z = 2; 4 is hexagonal, P6(5), a = 9.42530(10), b = 9.42530(10), c = 55.3713(5) A, alpha = 90, beta = 90, gamma = 120 degrees, Z = 6; 5 is monoclinic, P2/n, a = 14.1601(3), b = 13.1756(3), c = 27.1826(6) A, alpha = 90, beta = 90.1744(7), gamma = 90 degrees, Z = 2; 6 is monoclinic, P2/n, a = 14.2709(7), b = 13.2646(7), c = 27.4189(13) A, alpha = 90, beta = 90.3850(10), gamma = 90 degrees, Z = 2; 7 is monoclinic, P2/n, a = 14.2388(2), b = 13.1919(2), c = 26.7879(3) A, alpha = 90, beta = 90.0650(8), gamma = 90 degrees, Z = 2. PMID- 11782140 TI - Trivalent lanthanide compounds with fluorinated thiolate ligands: Ln-F dative interactions vary with Ln and solvent. AB - The fluorinated tris-thiolate compounds Ln(SC(6)F(5))(3) can be isolated as THF, pyridine, or DME coordination complexes. In THF, the larger Ce forms dimeric [(THF)(3)Ce(SC(6)F(5))(3)](2) (1) with bridging thiolate ligands, while the smaller lanthanides (Ln = Ho (2), Er (3)) form monometallic (THF)(3)Ln(SC(6)F(5))(3) compounds. There is a tendency for fluoride to coordinate to Ln throughout the lanthanide series (Ce-Er). The cerium compound 1 contains a pair of bridging thiolates connecting two eight-coordinate Ce(III) ions. Of the two terminal thiolates, only one exhibits a distinct Ce-F bond. In contrast, the Ho derivative (THF)(3)Ho(SC(6)F(5))(3) is a molecular compound in the solid state, with two monodentate thiolates and one thiolate that again coordinates through both S and F atoms. Incorporation of a stronger Lewis base reduces but does not necessarily eliminate the tendency to form Ln-F bonds. Structural characterization of the eight-coordinate (pyridine)(4)Sm(SC(6)F(5))(3) (4) reveals a single, clearly defined Ln-F interaction, while in (pyridine)(4)Yb(SC(6)F(5))(3) (5) there are no Yb-F bonds. In the structure of (DME)(2)Er(SC(6)F(5))(3) (6) the DME ligands completely displace F from the Er coordination sphere. PMID- 11782141 TI - Syntheses and crystal structures of two topologically related modifications of Cs(2)[(UO(2))(2)(MoO(4))(3)]. AB - Two polymorphs of Cs(2)(UO(2))(2)(MoO(4))(3) have been synthesized by hydrothermal (alpha-phase) and high-temperature (beta-phase) routes. Both were characterized by single-crystal X-ray diffraction: alpha Cs(2)(UO(2))(2)(MoO(4))(3), orthorhombic, Pna2(1), a = 20.4302(15) A, b = 8.5552(7) A, c = 9.8549(7) A, Z = 4; beta-Cs(2)(UO(2))(2)(MoO(4))(3), tetragonal, P4(2)/n, a = 10.1367(8) A, c = 16.2831(17) A, Z = 4. The structures of both phases consist of linked UO(7) pentagonal bipyramids and MoO(4) tetrahedra: alpha Cs(2)(UO(2))(2)(MoO(4))(3) is a framework compound with large channels parallel to the c axis. Two cesium sites are located in these channels and are coordinated by 8 and 10 oxygen atoms. The structure of beta-Cs(2)(UO(2))(2)(MoO(4))(3) contains corrugated [(UO(2))(2)(MoO(4))(3)] sheets that are parallel to (001). The cesium cations are located between the sheets and are coordinated by eight oxygen atoms. The structures are topologically related; both can be described in terms of chains of 5-connected UO(7) pentagonal bipyramids and 3- and 4-connected MoO(4) tetrahedra. PMID- 11782142 TI - Synthesis, characterization, photophysical properties, and biological labeling studies of a series of luminescent rhenium(I) polypyridine maleimide complexes. AB - We report the synthesis, characterization, and photophysical properties of a series of rhenium(I) polypyridine maleimide complexes [Re(N-N)(CO)(3)(py-3 mal)](CF(3)SO(3)) [N-N = 1,10-phenanthroline, phen (1), 2,9-dimethyl-1,10 phenanthroline, 2,9-Me(2)-phen (2), 3,4,7,8-tetramethyl-1,10-phenanthroline, 3,4,7,8-Me(4)-phen (3), 4,7-diphenyl-1,10-phenanthroline, 4,7-Ph(2)-phen (4), 2,9 dimethyl-4,7-diphenyl-1,10-phenanthroline, 2,9-Me(2)-4,7-Ph(2)-phen (5), 2,2' biquinonine, biq (6); py-3-mal = N-(3-pyridyl)maleimide]. The X-ray crystal structure of complex 2 has been investigated. Upon excitation, the complexes exhibit intense and long-lived photoluminescence in fluid solutions at 298 K. The emission wavelengths range from 514 to 654 nm, and the emission lifetimes fall in the microsecond time scale. The luminescence is assigned to originate from a metal-to-ligand charge-transfer MLCT [dpi(Re) --> pi*(diimine)] triplet excited state. As the maleimide group can react with the sulfhydryl group to form a stable thioether moiety, these complexes have been used as thiol-specific luminescent labels for a thiolated oligonucleotide, glutathione, and bovine serum albumin and human serum albumin. The photoluminescence properties of the labeled biological species have also been investigated. PMID- 11782143 TI - Molybdenum complexes with linked cycloheptatrienyl-phenolate ligands. AB - The tropylium salt (2-hydroxy-3,5-dimethylphenyl)cycloheptatrienylium tetrafluoroborate (3) has been synthesized in three steps from THP-protected 2,4 dimethylphenol and tropylium tetrafluoroborate, (C(7)H(7))BF(4). In CH(2)Cl(2) solution, the unexpected formation of tricyclic 2,4 dimethylbenzo[b]cyclohepta[d]furanylium tetrafluoroborate (5) has been observed, which must have formed from 3 by loss of H(2). 5 was characterized by an X-ray crystal structure determination and could independently be synthesized by treatment of 3 with NaHCO(3) to give 2,4-dimethylbenzo[b]cyclohepta[d]furan (4) followed by acidification with HBF(4).Et(2)O. The arene transfer reaction of 3 with [(eta-p-xylene)Mo(CO)(3)] furnished the cycloheptatrienyl complex [(HOC(6)H(2)Me(2)-eta(7)-C(7)H(6))Mo(CO)(3)]BF(4) (6), which could be converted into the chiral chelate complexes [(OC6H2Me2-eta7-C7H6)Mo(CO)(PR3)](9a, R = Ph; 9b, R = c-C(6)H(11); 9c, i-Pr) by subsequent treatment with NaI, PR(3), and NaH. The linked cycloheptatienyl-phenolate ligand in 9a could be protonated at the coordinated oxygen atom employing HBF(4).Et(2)O to yield [(HOC6H2Me2-eta7 C7H6)Mo(CO)(PPh3)]-BF4 (10). In 10, the appended phenol group is coordinated in a hemilabile fashion, which allowed the introduction of 2,6-dimethylphenyl isocyanide and CO and formation of complexes [(HOC(6)H(2)Me(2)-eta(7) C(7)H(6))Mo(CO)(PPh(3))L]BF(4) (11, L = XyNC; 12, L = CO). On thermal reaction of [(HOC(6)H(2)Me(2)-eta(7)-C(7)H(6))Mo(CO)(2)I] (7) with dppe, the addition of the diphosphine was observed together with the simultaneous formation of the molydenum-oxygen bond to yield [(OC6H2Me2-eta3-C7H6)Mo(CO)2(dppe)] (13), in which the cycloheptatrienyl ring has reduced its hapticity from seven to three. The pseudooctahedral complex 13 exhibits an interesting fluxional behavior in solution, which has been studied by means of variable-temperature (31)P and (1)H NMR spectroscopy. A eta(3) --> eta(7) hapticity reversion could be achieved by UV irradiation of a solution of 13 in THF to give the electron-rich complex [(OC6H2Me2-eta7-C7H6)Mo(dppe)] (14). 14 was readily oxidized with ferrocenium hexafluorophosphate, and the resulting paramagnetic monocationic complex 15 has been studied by means of ESR spectroscopy and X-ray diffraction. In addition, the X-ray crystal structures of complexes 9a, 10.2CH(2)Cl(2), 12, and 13 are reported. PMID- 11782144 TI - N-(ferrocenylmethyl)-N-methylaminocyclotriphosphazenes. AB - The reactions of N-(ferrocenylmethyl)-N-methylamine, C(5)H(5)FeC(5)H(4)CH(2)(Me)NH, with hexachlorocyclotriphosphazene, N(3)P(3)Cl(6), led to the formation of the N-(ferrocenylmethyl)-N-methylaminocyclotriphosphazene derivatives, N(3)(-)P(3)Cl(6-n)[N(Me)CH(2)C(5)H(4)FeC(5)H(5)](n) (n = 1-3). Only small amounts of higher degrees of substitution could be detected. In the case of the disubstituted products, the ratio of isomers was dependent on the polarity of the solvent. In nonpolar solvents the ratio was trans > geminal > cis while in acetonitrile only equal amounts of trans and cis isomers were observed. The reaction of N-(ferrocenylmethyl)-N-methylamine with (methacryloylbutenedioxy)pentachlorocyclotriphosphazene, N(3)P(3)Cl(5)O(CH(2))(4)OC(O)C(Me)=CH(2), gives the surprising geminal isomer 2,2 N(3)P(3)Cl(4)[O(CH(2))(4)OC(O)C(Me)=CH(2)]N(Me)CH(2)C(5)H(4)FeC(5)H(5) and the tris derivative 2,2',4 N(3)P(3)Cl(3)[O(CH(2))(4)OC(O)C(Me)=CH(2)][N(Me)CH(2)C(5)H(4)FeC(5)H(5)](2). All of the phosphazene derivatives were characterized by elemental analyses, mass spectrometry, IR and NMR ((1)H, (13)C, (31)P) spectroscopy, and electrochemical techniques (cyclic, normal pulse, and differential pulse voltametry). The compounds all undergo a single, reversible oxidation reduction process. PMID- 11782145 TI - Formation of metallaboranes from the group IV transition metals and pentaborane(9): crystal and molecular structure of [(Cp(2)Zr)(2)B(5)H(8)][B(11)H(14)]. AB - The reactions between [(C(5)H(5))(2)MCl(2)] (where M = Ti, Zr, Hf) and Li[B(5)H(8)] in a variety of solvents have been investigated. In the case of Zr, a pale orange solid, mu-(Cp(2)ClZr)B(5)H(8) (1), is formed in 70% yield. Compound 1 exists as a B(5)H(9) cage with a Cp(2)ClZr moiety replacing a bridging H atom. The variable temperature NMR spectra of 1 reveal two fluxional processes, one (DeltaG(++) = 54 kJ mol(-1)) which renders a plane of symmetry in the molecule and a higher temperature one (DeltaG(++) = 48 kJ mol(-1)) which renders all the basal B atoms equivalent. Dynamic processes are suggested to account for these observations. Passage of a CH(2)Cl(2) solution of 1 through silica gel affords 2, [(Cp(2)Zr)(2)B(5)H(8)][B(11)H(14)], a yellow, air-stable, crystalline solid, in 14% yield. The cation in 2, [(Cp(2)Zr)(2)B(5)H(8)](+), consists of a distorted spiro[2.2]pentane-like B(5) moiety comprising two B(3) triangles sharing a naked boron vertex. The two triangles are twisted 73 degrees with respect to each other, and the two [Cp(2)Zr] groups bond in a trihapto arrangement to the two opposite B-B-B edges. Each exterior B-Zr edge is H-bridged, and the B atoms possess terminal hydrogens. Reactions of Cp(2)HfCl(2) with Li[B(5)H(8)] lead to the formation of the analogue of 2, [(Cp(2)Hf)(2)B(5)H(8)][B(11)H(14)] (3). The precursor to 3, that is, the Hf analogue of 1, is not observed. Reaction between Li[B(5)H(8)] and Cp(2)TiCl(2) afforded no identifiable products, but reaction with CpTiCl(3) resulted in cage coupling and the formation of B(10)H(14). PMID- 11782146 TI - Synthesis and structural characterization of the [[Rh(5)(CO)(14)] (H(2)N(CH(2))(4)NH(2))-[Rh(5)(CO)(14)])](2-) and [Rh(5)(CO)(13)(H(2)N(CH(2))(2)NH(2))](-) anions (as [PPh(4)](+) salts): an unprecedented example of carbonyl substitution by alkylamines in a homoleptic metal carbonyl cluster anion. AB - The substitution of one or two carbonyls by many different primary and secondary alkylamines and -diamines has been established for the first time in a homoleptic carbonyl cluster anion, the trigonal bipyramidal [Rh(5)(CO)(15)](-). Two derivatives, the bis-monosubstituted [[Rh(5)(CO)(14)]-(H(2)N(CH(2))(4)NH(2)) [Rh(5)(CO)(14)]](2-) dianion (1) and the disubstituted chelated [Rh(5)(CO)(13)(H(2)N(CH(2))(2)NH(2))](-) monoanion (2), have been structurally characterized, both in the solid state (as [PPh(4)](+) salts) and in solution, revealing that the sites of the substitution are the cluster apexes. (13)C NMR spectra of 2 revealed localized fluxionality of the CO ligands over the temperature range 298-183 K. PMID- 11782147 TI - Syntheses, crystal structures, and density functional theory calculations of the closo-[1-M(CO)(3)(eta(4)-E(9))](4-) (E = Sn, Pb; M = Mo, W) cluster anions and solution NMR spectroscopic characterization of [1-M(CO)(3)(eta(4)-Sn(9))](4-) (M = Cr, Mo, W). AB - The closo-[1-M(CO)(3)(eta(4)-E(9))](4-) (E = Sn, Pb; M = Mo, W) anions have been obtained by extracting the binary alloys KSn(2.05) and KPb(2.26) in ethylenediamine (en) in the presence of 2,2,2-crypt or in liquid NH(3) followed by reaction with M(CO)(3).mes (M = Mo, W) or Cr(CO)(3).tol in en or liquid NH(3) solution. Crystallization of the molybdenum and tungsten salts was induced by vapor diffusion of tetrahydrofuran into the en solutions. The salts [2,2,2-crypt K](4)[1-M(CO)(3)(eta(4)-Sn(9))].en (M = Mo, W) crystallize in the triclinic system, space group P1, Z = 4, a = 16.187(3) A, b = 25.832(4) A, c = 29.855(5) A, alpha = 111.46(1) degrees, beta = 102.84(2) degrees, gamma = 92.87(2) degrees at 95 degrees C (M = Mo) and a = 17.018(3) A, b = 27.057(5) A, c = 28.298(6) A, alpha = 66.42(3) degrees, beta = 76.72(3) degrees, gamma = 87.27(3) degrees at 20 degrees C (M = W). The salts (CO)(3)M(en)(2)[2,2,2-crypt-K](4)[1-M(CO)(3)(eta(4) Pb(9))].2.5en (M = Mo, W) crystallize in the triclinic system, space group P1, Z = 2, a = 16.319(3) A, b = 17.078(3) A, c = 24.827(5) A, alpha = 71.82(3) degrees, beta = 83.01(3) degrees, gamma = 81.73(3) degrees at -133 degrees C (M = Mo) and a = 16.283(4) A, b = 17.094(3) A, c = 24.872(6) A, alpha = 71.62(2) degrees, beta = 82.91(2) degrees, gamma = 81.35(2) degrees at -153 degrees C (M = W). The [1 M(CO)(3)(eta(4)-Sn(9))](4-) anions were also characterized in liquid NH(3) solution by (119)Sn, (117)Sn, and (95)Mo NMR spectroscopy. Unlike their fluxional precursor, nido-Sn(9)(4-), NMR studies show that the [1-M(CO)(3)(eta(4)-Sn(9))](4 ) anions are rigid on the NMR time scale. All possible inter- and intraenvironmental couplings, J((119,117)Sn-(119,117)Sn), J((119,117)Sn-(183)W), and one J((119,117)Sn-(95)Mo) coupling, have been observed and assigned. Complete spin-spin coupling constant assignments were achieved by detailed analyses and simulations of all spin multiplets that comprise the (119)Sn and (117)Sn NMR spectra and that arise from natural abundance tin isotopomer distributions and from natural abundance (183)W, in the case of [1-W(CO)(3)(eta(4)-Sn(9))](4-). Both the solid state and solution structures of the [1-M(CO)(3)(eta(4)-Sn(9))](4 ) anions are based on a closo-bicapped square antiprismatic structure in which the transition metal occupies a cap position. The cluster structures are consistent with Wade's rules for 22 (2n + 2) skeletal electron systems. Electron structure calculations at the density functional theory (DFT) level provide fully optimized geometries that are in agreement with the experimental structures. Complete assignment of the NMR spectra was also aided by GIAO calculations. The calculated vibrational frequencies of the E(9)(4-) and [1-M(CO)(3)(eta(4) E(9))](4-) anions are also reported and are used to assign the solid-state vibrational spectra of the [1-M(CO)(3)(eta(4)-E(9))](4-) anions. PMID- 11782148 TI - Bromite ion catalysis of the disproportionation of chlorine dioxide with nucleophile assistance of electron-transfer reactions between ClO(2) and BrO(2) in basic solution. AB - The rate of ClO(2) conversion to ClO(2)(-) and ClO(3)(-) is accelerated by BrO(2)(-), repressed by ClO(2)(-), and greatly assisted by many nucleophiles (Br( ) > PO(4)(3-) > HPO(4)(2-) > CO(3)(2-) > Cl(-) approximately OH(-) > CH(3)COO(-) approximately SO(4)(2-) approximately C(5)H(5)N >> H(2)O). The kinetics (at p[H(+)] = 9.3-12.9) show that the first step of the mechanism is an electron transfer between ClO(2) and BrO(2)(-) (k(1) = 36 M(-1) s(-1)) to give ClO(2)(-) and BrO(2). This highly reversible reaction (k(1)/k(-1) = 1 x 10(-6)) accounts for the observed inhibition by ClO(2)(-). The second step is an electron transfer between ClO(2) and BrO(2) to regenerate BrO(2)(-) and form ClO(3)(-). A novel aspect of the second step is the large kinetic contribution from nucleophiles (k(Nu)) that assist the electron transfer between ClO(2) and BrO(2). The k(Nu) (M(-2) s(-1)) values at 25.0 degrees C vary from 2.89 x 10(8) for Br(-) to 2.0 x 10(4) for H(2)O. PMID- 11782149 TI - Kinetics and mechanism of ligand interchange in pentacyano-L-osmate(II) complexes (L = H(2)O, NH(3), N-heterocyclic ligands). AB - The new complex, K(3)[Os(CN)(5)NH(3)].2H(2)O, a convenient precursor for the pentacyano-L-osmate(II) series, was prepared and characterized by chemical analysis, cyclic voltammetry, and IR and UV-vis spectroscopies. By controlled aquation in weakly acidic medium, the [Os(CN)(5)H(2)O](3-) ion was generated. Weak absorptions in the UV region for L = H(2)O, NH(3), and CN(-) were found at 287, 272, and 240 nm, respectively, and were assigned to d-d transitions, in terms of a model for tetragonally distorted ions also valid for the members of the iron and ruthenium series. The kinetics of the formation and dissociation reactions of the [Os(CN)(5)L](n-) ions, L = pyridine (py), pyrazine (pz), N methylpyrazinium (mpz(+)), etc., were studied. At 25.0 degrees C, the formation rate constants for the neutral ligands pz and isonicotinamide were ca. 0.13 M(-1) s(-1) and slightly increased for L = mpz(+) and decreased for isonicotinate. The enthalpies of activation were ca. 22.0 kcal mol(-1), independently of the entering L, and the activation entropies were all positive, ca. 11-13 cal K(-1) mol(-1). The dissociation reactions showed a saturation rate behavior of k(obs) (s(-1)) as a function of the concentration of the scavenger ligand. The specific dissociation rate constant at 25.0 degrees C was 1.06 x 10(-7) s(-1) for L = NH(3) and around 10(-9) s(-1) for py, pz, and mpz(+) (extrapolated to 25.0 degrees C from values measured in the range 60-95 degrees C). These small values are associated with high activation enthalpies (range 30-35 kcal mol(-1)) and positive activation entropies (range 10-20 cal K(-1) mol(-1)). The evidence for both the formation and dissociation processes shows that dissociative mechanisms are operative, as for the iron and ruthenium analogues. PMID- 11782150 TI - Chalcogen rich lanthanide clusters from halide starting materials (II): selenido compounds. AB - Lanthanides reduce mixtures of I(2) and PhSeSePh in THF, and the resultant heteroligand mixture reacts further with elemental Se in pyridine to give (THF)(6)Ln(4)I(2)(SeSe)(4)(mu(4)-Se).THF (Ln = Tm, Ho, Er, Yb). These selenium rich clusters contain a square array of Ln(III) ions connected through a single (mu(4)-Se) ligand. There are two I(-) ligands coordinating nonadjacent Ln(III) ions on the side of the cluster opposite the (mu(4)-Se), and the edges of the square are bridged by mu(2)-SeSe groups. The electronic spectrum of the Yb compound contains two absorption maxima that can tentatively be assigned as Se(2 ) to Yb and SeSe to Yb charge-transfer absorptions, by comparison with the featureless absorption spectra of the Tm, Ho, and Er derivatives. With a 1/1/1/1 Yb/I/Ph(2)S(2)/Se stoichiometry, chalcogen rich compounds are not obtained, but instead, in Yb chemistry, the selenido cluster (THF)(10)Yb(6)Se(6)I(6) can be isolated in 51% yield. The molecular structure of this compound contains a Yb(4)Se(4) cubane fragment, with an additional Yb(2)Se(2) layer capping one face of the cube. Each Yb coordinates a terminal I(-). This intensely colored compound also has an absorption maximum in the visible spectrum. Upon thermolysis, the selenium rich compounds give Ln(2)Se(3) that is free of iodide contamination. PMID- 11782151 TI - Ferrocene bis(phosphonite)s: synthesis and characterization of a novel class of sterically congested ligands. PMID- 11782153 TI - Electrochemistry of cycloaddition products of olefins with nickel dithiolenes: a reinvestigation of the reduction of the 1:1 adduct between Ni(S(2)C(2)(CF(3))(2))(2) and norbornadiene. PMID- 11782152 TI - Photophysical and photochemical properties of W(0) and Re(i) carbonyl complexes incorporating ferrocenyl-substituted pyridine ligands. PMID- 11782154 TI - Hydrothermal synthesis and crystal structure of a novel two-dimensional vanadium oxide complex with a 6,14-net sinusoidal ruffling anionic layer: [Ni(phen)(2)V(4)O(11)] (phen = 1,10-phenanthroline). PMID- 11782155 TI - Synthesis and characterization of Cs(5)P[Mo(4)O(14)(OH)](2).2H(2)O: a new molybdophosphate cluster with face-sharing MoO(6) octahedra. PMID- 11782156 TI - Coupling of edge-sharing bioctahedral dirhenium(II) units through the agency of [N(CN)(2)](-), [C(CN)(3)](-), and [Ni(CN)(4)](2-) linkages. PMID- 11782157 TI - Can semiempirical quantum mechanics be used to predict the spin state of transition metal complexes? An application of de novo prediction. PMID- 11782158 TI - Direct observation of host-guest hydrogen bonding in the zeolite NaY/chloroform system by neutron scattering. AB - The differential H pair distribution function obtained from neutron scattering contrast measurements on hydrogenous and deuterated chloroform adsorbed into zeolite NaY (two molecules per supercage) reveals direct evidence for hydrogen bonding between hydrogen atoms on the sorbate molecule and oxygen atoms of the zeolite framework. A vector between the hydrogen and framework Si/Al atoms is also observed. The results confirm the conclusions drawn from previous vibrational spectroscopy and computer modeling studies. PMID- 11782159 TI - Single-molecule precipitation of transition metal(I) chlorides in water clusters. AB - Metal ions in unusual oxidation states can be introduced into water clusters using a standard laser vaporization source. Such nanosolutions of a single ion in typically 50 water molecules are comparable to a 1 M bulk solution, and their chemistry can be studied in the ion trap of a Fourier transform ion cyclotron resonance mass spectrometer. We find that a strong acid like hydrogen chloride oxidizes the early transition metal vanadium to the more common +III state, while later first row transition metals retain their unusual +I oxidation state, and the binary metal chlorides M(I)Cl precipitate. PMID- 11782160 TI - A mild and efficient catalytic alkylative monofunctionalization of cyclic anhydrides. AB - Substituted succinic and glutaric anhydrides undergo a nickel-catalyzed monofunctionalization with organozinc reagents as nucleophiles. The reaction proceeds readily with a variety of substrates, employs commercially available or readily attainable reagents, tolerates sensitive functionality on both partners, and affords the product ketoacids in moderate to high yields. The use of a chiral phosphinooxazoline results in a desymmetrization of a meso anhydride to provide the ketoacid in 85% yield and 79% ee. PMID- 11782161 TI - A new and efficient method for the selective olefination of aldehydes with ethyl diazoacetate catalyzed by an iron(II) porphyrin complex. AB - Olefination of aromatic and aliphatic aldehydes with ethyl diazoacetate was achieved in excellent yields with triphenylphosphine and catalytic amounts of iron(II) meso-tetra(p-tolyl)porphyrin. The reaction conditions are mild and the process is efficient and highly selective (>90%) for the synthesis of the trans olefin isomer. Results of mechanistic studies are discussed. PMID- 11782162 TI - Novel synthesis and characterization of five isomers of (C(70))(2) fullerene dimers. AB - The synthesis and characterization of dimers and polymers, wherein two or more cages are linked, represent an important frontier in the chemistry of fullerene derivatives. A simple and novel method that requires no special apparatus has been developed for the dimerization of [70]fullerene to (C70)2. Upon grinding [70]fullerene in a mortar and pestle in the presence of K2CO3, five structural isomers of (C70)2 have been produced. These isomers are separated from one another via high performance liquid chromatography and are characterized by 13C NMR, UV-vis-NIR absorption and mass spectroscopy. PMID- 11782163 TI - A general strategy to determine a target DNA sequence of a short peptide: application to a d-peptide. AB - Short peptides could potentially provide a novel element to read-out DNA sequences from the major groove. However, it is difficult to determine sequence preference of de novo designed monomeric short peptides. Because DNS-binding affinity and specificity of short peptides are usually much lower than those of native DNA-binding proteins, determining the sequence-preference of short peptides by conventional methods utilized to deduce the target sequence of proteins often produces an unclear outcome. We report here a general strategy to defining the sequence-preference of a DNA-binding short peptide by using the heterodimers. A GCN4 basic region peptide tethers a low-affinity DNA-binding peptide adjacent to a GCN4 binding sequence through the cyclodextrin-adamantane association, thereby increasing local concentration of the low-affinity peptide on degenerated DNA sequences. An increase of the local concentration allows one to select a preferential sequence for the low-affinity DNA binding peptide. The method successfully identified specific sequences of short peptides derived from native DNA-binding proteins. The usefulness of this approach has been demonstrated by identifying preferred DNA targets for a peptide composed only of d-amino acids. The method is potentially applicable not only to artificial peptides, but also to other synthethic ligands. PMID- 11782164 TI - Crystallographic evidence for oxygen acceptor directionality in oxyanion hydrogen bonds. AB - A survey of 2632 D-H...O-A hydrogen bonds in crystal structures (where D is any atom and A is the central atom of a trigonal planar (A = C, N) or tetrahedral (A = P, S, Cl, As, Se, Cr, Mo) oxyanion, has established the existence of a distinct directionalities at the oxygen atom acceptors. The directionality depends primarily on the geometry of the oxyanion. With the trigonal planar oxyanions NO3 , HCO3-, and CO32-, the average H...O-A angle is 115 +/- 12 degrees and there is a clear preference for the hydrogen to lie within the plane of the anion. With the tetrahedral oxyanions H2PO4-, HPO42-, HSO4-, SO42-, ClO4-, H2AsO4-, HAsO42-, AsO43-, HSeO4-, SeO42-, CrO42-, and MoO42-, the average H...O-A angle is 122 +/- 12 degrees , and there is a weak preference for eclipsed H...O-X-O dihedral angles. The observed directionality closely coincides with minima on electrostatic potential surfaces calculated for the anions. PMID- 11782165 TI - A highly enantioselective intramolecular Heck reaction with a monodentate ligand. AB - An efficient enantioselective intramolecular Heck reaction of cyclohexadienones, using readily available and modular TADDOL-based mono- and bidentate phosphoramidites as chiral ligands and not requiring any additives, has been developed. Excellent enantioselectivities up to 96% ee are reached for the first time in a Heck reaction with monodentate ligands. PMID- 11782166 TI - Ruthenium-catalyzed intramolecular oxidative amination of aminoalkenes enables rapid synthesis of cyclic imines. AB - [RuCl2(CO)3]2/dppp is shown to be a highly effective catalyst system for the first intramolecular oxidative amination of a variety of aminoalkenes when it is used concomitantly with K2CO3 and allyl acetate in N-methylpiperidine, to give the corresponding cyclic imines and indoles in excellent yields. For example, the reaction of 2,2-diphenyl-4-pentenyl-1-amine performed in the presence of 2 mol % of [RuCl2(CO)3]2, 4 mol % of dppp, K2CO3, and allyl acetate in N-methylpiperidine at 140 degrees C for 8 h gives 4,4-diphenyl-2-methyl-1-pyrroline in quantitative (>99%) yield. PMID- 11782167 TI - Oxidative addition of water to novel Ir(I) complexes stabilized by dimethyl sulfoxide ligands. AB - The oxidative addition of water to novel Ir(I) DMSO complexes is described. IrCl(DMSO)3 (1) is synthesized in 90% yield when treating a toluene slurry of [Ir2Cl2(COE)4] (COE = cyclooctene) with excess DMSO. Its dimer, [Ir2Cl2(DMSO)4] (2) is obtained in 95% yield starting from 1. The cationic complex [Ir(DMSO)4]PF6 (6) is prepared in situ from [Ir(COE)2(O=CMe2)2]PF6 (5). These complexes add water at room temperature, giving rise to the oxidative addition products syn [(DMSO)2HIr(mu-OH)2(mu-Cl)IrH(DMSO)2] [IrCl2(DMSO)2] (3) and anti [(DMSO)2(DMSO)HIr(mu-OH)2IrH(DMSO)2(DMSO)](PF6)2 (7), respectively. Reductive elimination in pyridine leads to quantitative isolation of mixed Ir(I) DMSO pyridine complexes IrCl(py)(DMSO)2 (4) and [Ir(py)2(DMSO)2]PF6 (8), respectively. Compounds 1, 3, and 7 have been characterized by X-ray crystallography. 3 and 7 show dimeric structures with the hydroxo ligands bridging the iridium atoms and in 7 both O- and S-bonded DMSO ligands are present. PMID- 11782168 TI - An enantioselective total synthesis of (+)- and (-)-saudin. Determination of the absolute configuration. AB - A short efficient enantioselective synthesis of both (+)- and (-)-saudin, a naturally occurring hypoglycemic diterpene, is described. This synthesis establishes the absolute configuration of natural (-)-saudin for the first time. The key steps include the enantioselective construction of a dimethyl Hagemann's ester by an asymmetric Michael reaction and establishment of the key 1,3 disposed quaternary centers by means of a novel Ti(IV) promoted Claisen rearrangement. The assembly of the polycyclic ketal skeleton was likely under kinetic control proceeding via formation of the C1oxygen-C7 bond through an oxonium ion intermediate in the final stage. PMID- 11782169 TI - Effects of the protein environment on the structure and energetics of active sites of metalloenzymes. ONIOM study of methane monooxygenase and ribonucleotide reductase. AB - As the first application of our recently developed ONIOM2(QM:MM) and ONIOM3(QM:QM:MM) codes to the metalloenzymes with a large number of protein residues, two members of the non-heme protein family, methane monooxygenause and ribonucleotide reductase, have been chosen. The "active-site + four alpha-helical fragments" model was adopted which includes about 1000 atoms from 62 residues around the Fe-centered spheres. Comparison of the active-site geometries of MMOH and R2 units optimized with this model with those obtained with the "active site only" (with only 39-46 atoms) model and the X-ray results clearly demonstrates the crucial role of the active site-protein interaction in the enzymatic activities. PMID- 11782170 TI - Structural characterization of a photoinduced molecular switch. AB - The crystal structures in both irradiated and nonirradiated states of a photoinduced molecular switch based on the spin-crossover phenomenon are presented. From the structural point of view, the light-induced metastable high spin state of the spin-crossover complex [Fe(phen)2(NCS)2] (phen = 1,10 phenanthroline) shows significant differences with the low-spin state but also with the thermally induced high-spin state. PMID- 11782171 TI - Dimers of dipyrrometheneboron difluoride (BODIPY) with light spectroscopic applications in chemistry and biology. AB - A ground-state dimer (denoted D(I)) exhibiting a strong absorption maximum at 477 nm (epsilon = 97 000 M(-1)cm(-1)) can form between adjacent BODIPY groups attached to mutant forms of the protein, plasminogen activator inhibitor type 1 (PAI-1). No fluorescence from excited D(I) was detected. A locally high concentration of BODIPY groups was also achieved by doping lipid phases (micelles, vesicles) with BODIPY-labeled lipids. In addition to an absorption band located at about 480 nm, a new weak absorption band is also observed at ca. 570 nm. Both bands are ascribed to the formation of BODIPY dimers of different conformation (D(I) and D(II)). Contrary to D(I) in PAI-1, the D(II) aggregates absorbing at 570 nm are emitting light observed as a broad band centered at about 630 nm. The integrated absorption band of D(I) is about twice that of the monomer, which is compatible with exciton coupling within a dimer. The Forster radius of electronic energy transfer between a BODIPY excited monomer and the ground-state dimer (D(I)()) is 57 +/- 2 A. A simple model of exciton coupling suggests that in D(I) two BODIPY groups are stacked on top of each other in a sandwich-like configuration with parallel electronic transition dipoles. For D(II) the model suggests that the S(0) --> S(1) transition dipoles are colinear. An explanation for the previously reported (J. Am. Chem. Soc. 1994, 116, 7801) exceptional light spectroscopic properties of BODIPY is also presented. These are ascribed to the extraordinary electric properties of the BODIPY chromophore. First, changes of the permanent electric dipole moment (Delta(mu) approximately 0.05 D) and polarizability (-26 x 10(-40) C m(2) V(-1)) between the ground and the first excited states are small. Second, the S(0) <--> S(1) electronic transition dipole moments are perpendicular to Delta(mu). PMID- 11782172 TI - Calorimetric and structural studies of 1,2,3-trisubstituted cyclopropanes as conformationally constrained peptide inhibitors of Src SH2 domain binding. AB - Isothermal titration calorimetry and X-ray crystallography have been used to determine the structural and thermodynamic consequences associated with constraining the pTyr residue of the pYEEI ligand for the Src Homology 2 domain of the Src kinase (Src SH2 domain). The conformationally constrained peptide mimics that were used are cyclopropane-derived isosteres whereby a cyclopropane ring substitutes to the N-Calpha-Cbeta atoms of the phosphotyrosine. Comparison of the thermodynamic data for the binding of the conformationally constrained peptide mimics relative to their equivalent flexible analogues as well as a native tetrapeptide revealed an entropic advantage of 5-9 cal mol(-1) K(-1) for the binding of the conformationally constrained ligands. However, an unexpected drop in enthalpy for the binding of the conformationally constrained ligands relative to their flexible analogues was also observed. To evaluate whether these differences reflected conformational variations in peptide binding modes, we have determined the crystal structure of a complex of the Src SH2 domain bound to one of the conformationally constrained peptide mimics. Comparison of this new structure with that of the Src SH2 domain bound to a natural 11-mer peptide (Waksman et al. Cell 1993, 72, 779-790) revealed only very small differences. Hence, cyclopropane-derived peptides are excellent mimics of the bound state of their flexible analogues. However, a rigorous analysis of the structures and of the surface areas at the binding interface, and subsequent computational derivation of the energetic binding parameters, failed to predict the observed differences between the binding thermodynamics of the rigidified and flexible ligands, suggesting that the drop in enthalpy observed with the conformationally constrained peptide mimic arises from sources other than changes in buried surface areas, though the exact origin of the differences remains unclear. PMID- 11782173 TI - Synthesis and characterization of sulfur-voided cubanes. Structural analogues for the MoFe(3)S(3) subunit in the nitrogenase cofactor. AB - A new class of Mo/Fe/S clusters with the MoFe(3)S(3) core has been synthesized in attempts to model the FeMo-cofactor in nitrogenase. These clusters are obtained in reactions of the (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et (I), (n)Pr (II)] clusters with CO. The new clusters include those preliminarily reported: (Cl(4)-cat)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (III), (Cl(4) cat)(O)MoFe(3)S(3)(PEt(3))(3)(CO)(5) (IV), (Cl(4) cat)(Pyr)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (VI), and (Cl(4) cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(4) (VIII). In addition the new (Cl(4) cat)(O)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(5) cluster (IVa), the (Cl(4) cat)(O)MoFe(3)S(3)(PEt(3))(2)(CO)(6)cluster (V), the (Cl(4) cat)(O)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (Va), the (Cl(4) cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VIa), and the (Cl(4) cat)(P(n)Pr(3))MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VII) also are reported. Clusters III-VIII have been structurally and spectroscopically characterized. EPR, zero-field (57)Fe-Mossbauer spectroscopic characterizations, and magnetic susceptibility measurements have been used for a tentative assignment of the electronic and oxidation states of the MoFe(3)S(3) sulfur-voided cuboidal clusters. A structural comparison of the clusters with the MoFe(3)S(3) subunit of the FeMo-cofactor has led to the suggestion that the storage of reducing equivalents into M-M bonds, and their use in the reduction of substrates, may occur with the FeMo-cofactor, which also appears to have M-M bonding. On the basis of this argument, a possible N(2)-binding and reduction mechanism on the FeMoco-cofactor is proposed. PMID- 11782174 TI - The effect of mechanical interlocking on crystal packing: predictions and testing. AB - The first statistical analyses of the X-ray crystal structures of mechanically interlocked molecular architectures, the first molecular mechanics-based solid state calculations on such structures and atomic force microscopy (AFM) experiments are used in combination to predict and test which types of benzylic amide macrocycle-containing rotaxanes possess mobile components in the crystalline phase and thus could form the basis of solid-state devices that function through mechanical motion at the molecular level. The statistical studies and calculations show that crystals formed by rotaxanes possess similarities and unanticipated differences with respect to the crystal packing of noninterlocked molecules. Trends in the rotaxane series correlate quantities related to crystal packing, molecular size, stoichiometry, and H-bonding. In accordance with the findings of Gavezzotti et al. for conventional molecular architectures, a principal component analysis (PCA) showed that three vectors related to the size, packing parameters, and stoichiometry are sufficient to describe the crystal properties of benzylic amide macrocycle-containing rotaxanes. When hydrogen bond-related quantities are included in a second PCA, they combine with the size and the stoichiometry vectors but not with packing related parameters, indicating that the intramolecular "saturation" of the H bonds (between the interlocked components) takes precedence over crystal assembly (i.e., intermolecular packing) in these systems. However, cluster analyses also suggest a major role for the energy of interaction between the macrocycle and its crystal environment. The identification of such a "privileged" interaction is of fundamental importance to the development of rotaxanes with in-crystal mobility of one or more of their interlocked components, a prerequisite for the exploitation of molecular level mechanical motion in the solid state. The set of trends found, together with the calculated energies, was used to propose guidelines for which benzylic amide macrocycle-containing rotaxanes are best suited to become building blocks for systems with mobile submolecular units in the crystalline phase. An experimental test of the predictive power of such guidelines was carried out using AFM on a rotaxane and its thread, identified by the study as a promising candidate for solid-state mobility. Intuitively, the rotaxane should be less mobile in the solid state since it has multiple sets of both hydrogen bond donors and acceptors that can form strong inter- and intramolecular H-bonds. Conversely, the thread has no hydrogen bond donors and cannot form such bonds. The AFM experiments, however, confirm the statistical analysis prediction that the rotaxane is considerably more mobile in the solid than the thread. PMID- 11782175 TI - Product distribution of peroxynitrite decay as a function of pH, temperature, and concentration. AB - The decay of peroxynitrite [O=NOO(-), oxoperoxonitrate(1-)] was examined as a function of concentration (0.050-2.5 mM), temperature (5-45 degrees C), and pH (2.2-10.0). Below 5 degrees C and pH 7, little amounts of the decomposition products nitrite and dioxygen are formed, even when the peroxynitrite concentration is high (2.5 mM). Instead, approximately > or =90% isomerizes to nitrate. At higher pH, decomposition increases at the expense of isomerization, up to nearly 80% at pH 10.0 at 5 degrees C and 90% at 45 degrees C. Much less nitrite and dioxygen per peroxynitrite are formed when the peroxynitrite concentration is lower; at 50 microM and pH 10.2, < or =40% decomposes. In contrast to two other reports (Pfeiffer, S.; Gorren, A. C. F.; Schmidt, K.; Werner, E. R.; Hansert, B.; Bohle, D. S.; Mayer, B. J. Biol. Chem. 1997, 272, 3465-3470, and Coddington, J. W.; Hurst, J. K.; Lymar, S. V. J. Am. Chem. Soc. 1999, 121, 2438-2443), we find that the extent of decomposition is dependent on the peroxynitrite concentration. PMID- 11782176 TI - Mediated electrochemistry of horseradish peroxidase. Catalysis and inhibition. AB - A precise determination of the complex mechanism of catalysis and inhibition involved in the reaction of HRP with H(2)O(2) as substrate and an outersphere single electron donor ([Os(bpy)(2)pyCl](+)) as cosubstrate is made possible by a systematic analysis of the cyclic voltammetric responses as a function of the scan rate and of the substrate and cosubstrate concentrations, complemented by spectrophotometric steady-state and stopped-flow experiments. The bell-shaped calibration curve relating the electrochemical response to the concentration of H(2)O(2) is qualitatively and quantitatively explained by taking into account the conversion of the catalytically active forms of the enzyme into the inactive oxyperoxidase in addition to the primary catalytic cycle. These characteristics should be kept in mind in biosensor applications of HRP. The ensuing analysis and data allow one to predict biosensor amperometric responses in all practical cases. From a mechanistic standpoint, conditions may, however, be defined which render inhibition insignificant, thus allowing an electrochemical characterization of the primary catalytic cycle. At very low concentrations of H(2)O(2), its diffusion tends to control the electrochemical response, resulting in proportionality with H(2)O(2) concentration instead of the square root dependence characteristic of the classical catalytic currents. Intriguing hysteresis and trace crossings behaviors are also quantitatively explained in the framework of the same mechanism. As a consequence of the precise dissection of the rather complex reaction mechanism into its various elementary steps, a strategy may be devised for gaining a better understanding of the mechanism and reactivity patterns of each elementary step. PMID- 11782177 TI - A joint structural, kinetic, and thermodynamic investigation of substituent effects on host-guest complexation of bicyclic azoalkanes by beta-cyclodextrin. AB - Derivatives of the azoalkane 2,3-diazabicyclo[2,2,2]oct-2-ene (1a) with bridgehead 1,4-dialkyl (1b), 1,4-dichloro (1c), 1-hydroxymethyl (1d), 1 aminomethyl (1e), and 1-ammoniummethyl (1f) substituents form host-guest inclusion complexes with beta-cyclodextrin. They were employed as probes to assess substituent effects on the kinetics and thermodynamics of this complexation by using time-resolved and steady-state fluorimetry, UV spectrophotometry, induced circular dichroism (ICD) measurements, and (1)H NMR spectroscopy. The kinetic analysis based on quenching of the long-lived fluorescence of the azoalkanes by addition of host provided excited-state association rate constants between 2.6 x 10(8) and 7.0 x 10(8) M(-)(1) s(-)(1). The binding constants for 1a (1100 M(-1)), 1b (900 M(-1)), 1c (1900 M(-1)), 1d (180 M(-1)), 1e (250 M(-1)), and 1f (ca. 20 M(-1)) were obtained by UV, NMR, and ICD titrations. A positive ICD signal of the azo absorption around 370 nm was observed for the beta-cyclodextrin complexes of 1a, 1d, and 1f with the intensity order 1a >> 1d approximately 1f, and a negative signal was measured for those of 1b, 1c, and 1e with the intensity order 1c < 1b approximately 1e. The ICD was employed for the assignment of the solution structures of the complexes, in particular the relative orientation of the guest in the host (co-conformation). PMID- 11782178 TI - Consequences of correlated solvation on the structures and reactivities of RLi diamine complexes: 1,2-addition and alpha-lithiation reactions of imines by TMEDA solvated n-butyllithium and phenyllithium. AB - 6Li and (13)C NMR spectroscopic studies were carried out on [(6)Li]n-BuLi and [(6)Li]PhLi (RLi) in toluene-d(8) containing the following diamines: N,N,N',N' tetramethylethylenediamine (TMEDA), N,N,N',N'-tetraethylethylenediamine, 1,2 dipyrrolidinoethane, 1,2-dipiperidinoethane, N,N,N',N'-tetramethylpropanediamine, trans-(R,R)-N,N,N',N'-tetramethylcyclohexanediamine, and (-)-sparteine. Dimers of general structure (RLi)(2)S(2) (S = chelating diamine) are formed in each case. Treatment of RLi with two different diamines (S and S') affords homosolvates (RLi)(2)S(2) and (RLi)(2)S'(2) along with a heterosolvate (RLi)(2)SS'. Relative binding constants and associated free energies for the sequential solvent substitutions are obtained by competing pairs of diamines. The high relative stabilities of certain heterosolvates indicate that solvent binding to the RLi dimer can be highly correlated. Rate studies of both the 1,2-addition of RLi/TMEDA to the N-isopropylimine of cyclohexane carboxaldehyde and the RLi/TMEDA mediated alpha-lithiation of the N-isopropylimine of cyclohexanone reveal monomer based transition structures, [(RLi)(TMEDA)(imine)], in all cases. The complex relationships of solvent binding constants and relative reactivities toward 1,2 additions and alpha-lithiations are discussed. PMID- 11782179 TI - Cu(II)-mediated intramolecular carbene cation radical formation: relevance to unimolecular metal-ligand radical intermediates. AB - We report the syntheses of the photochemically labile 9-diazo-4,5-diazafluorene (1) framework and the corresponding Cu(9-diazo-4,5-diazafluorene)(2)(NO(3))(2) compound (2). The X-ray structure of 2 reveals a 6-coordinate, tetragonal geometry with one nitrogen donor of an asymmetrically chelated diazafluorene in the equatorial position and the other defining the weak Jahn-Teller axis. The nitrate counterions bind in a monodentate fashion in the equatorial plane to complete the coordination sphere. Extended Huckel calculations reveal that the unusual solid-state structure derives from the enlarged bite angle of the fluorene skeleton and steric interactions between the adjacent hydrogen atoms in the higher energy (0.45 eV) symmetrically coordinated state. This is in contrast to Cu(py)(4)(NO(3))(2) which is 1.3 eV more stable with the nitrate counterions bound along the Jahn-Teller axis. Electron paramagnetic resonance (EPR) studies in solution reveal that the nitrates dissociate to yield 6-coordinate CuN(2)X(2)N(2)' structures with either a bound chloride ion (g(x) = 2.10, g(y) = 2.04, g(z) = 2.23, A(z) = 177 x 10(-4) cm(-1)) or a mixture of counterion and solvent (g(x)(a) = 2.05, g(y)(a) = 2.06, g(z)(a) = 2.29, A(z)(a) = 170 x 10(-4) cm(-1); g(x)(b) = 2.07, g(y)(b) = 2.08, g(z)(b) = 2.34, A(z)(b) = 155 x 10(-4) cm(-1)). Photolyses of 1 and 2 indicate loss of N(2) and formation of either carbene ([D/hc] = 0.408 cm(-1), [E/hc] = 0.0292 cm(-1)) or Cu(I)-L(*)(+) (S = (1)/(2), g = 2.0019) intermediates, which are identified by EPR, UV-vis, and time dependent density functional theory methods. The results illustrate the important role redox active transition metals play in determining the nature of fundamental metal-ligand radical intermediates. PMID- 11782180 TI - 17O ENDOR detection of a solvent-derived Ni-(OH(x))-Fe bridge that is lost upon activation of the hydrogenase from Desulfovibrio gigas. AB - Crystallographic studies of the hydrogenases (Hases) from Desulfovibrio gigas (Dg) and Desulfovibrio vulgaris Miyazaki (DvM) have revealed heterodinuclear nickel-iron active centers in both enzymes. The structures, which represent the as-isolated (unready) Ni-A (S = (1)/(2)) enzyme state, disclose a nonprotein ligand (labeled as X) bridging the two metals. The bridging atom was suggested to be an oxygenic (O(2)(-) or OH(-)) species in Dg Hase and an inorganic sulfide in DvM Hase. To determine the nature and chemical characteristics of the Ni-X-Fe bridging ligand in Dg Hase, we have performed 35 GHz CW (17)O ENDOR measurements on the Ni-A form of the enzyme, exchanged into H(2)(17)O, on the active Ni-C (S = (1)/(2)) form prepared by H(2)-reduction of Ni-A in H(2)(17)O, and also on Ni-A formed by reoxidation of Ni-C in H(2)(17)O. In the native state of the protein (Ni-A), the bridging ligand does not exchange with the H(2)(17)O solvent. However, after a reduction/reoxidation cycle (Ni-A --> Ni-C --> Ni-A), an (17)O label is introduced at the active site, as seen by ENDOR. Detailed analysis of a 2-D field-frequency plot of ENDOR spectra taken across the EPR envelope of Ni A((17)O) shows that the incorporated (17)O has a roughly axial hyperfine tensor, A((17)O) approximately [5, 7, 20] MHz, discloses its orientation relative to the g tensor, and also yields an estimate of the quadrupole tensor. The substantial isotropic component (a(iso)((17)O) approximately 11 MHz) of the hyperfine interaction indicates that a solvent-derived (17)O is indeed a ligand to Ni and thus that the bridging ligand X in the Ni-A state of Dg Hase is indeed an oxygenic (O(2)(-) or OH(-)) species; comparison with earlier EPR results by others indicates that the same holds for Ni-B. The small (57)Fe hyperfine coupling seen previously for Ni-A (A((57)Fe) approximately 0.9 MHz) is now shown to persist in Ni-C, A((57)Fe) approximately 0.8 MHz. However, the (17)O signal is lost upon reductive activation to the Ni-C state; reoxidation to Ni-A leads to the reappearance of the signal. Consideration of the electronic structure of the EPR-active states of the dinuclear center leads us to suggest that the oxygenic bridge in Ni-A(B) is lost in Ni-C and is re-formed from solvent upon reoxidation to Ni-A. This implies that the reductive activation to Ni-C opens Ni/Fe coordination sites which may play a central role in the enzyme's activity. PMID- 11782181 TI - Computational assessment of the electronic structures of cyclohexa-1,2,4-triene, 1-oxacyclohexa-2,3,5-triene (3delta(2)-pyran), their benzo derivatives, and cyclohexa-1,2-diene. An experimental approach to 3delta(2)-pyran. AB - The six-membered cyclic allenes given in the title have been studied theoretically by means of an MR-CI approach. For all compounds, the allene structures were found to be the ground states in the gas phase. In the cases of cyclohexa-1,2-diene (1), the isobenzene 2, and the isonaphthalene 7, the most stable structures having a planar allene moiety are the diradicals 1b, 2b, and 7b, representing the transition states for the racemization of 1a, 2a, and 7a and being less stable than the latter by 14.1, 8.9, and 11.2 kcal/mol, respectively. At variance with this order, the 3delta(2)-pyran 4 and the chromene 5 have the zwitterions 4c and 5c as the most stable planar structures, which lie only 1.0 and 5.4 kcal/mol above 4a and 5a, respectively. According to the simulation of the solvent effect, 4c even becomes the ground state of 4 in THF solution. The frontier orbitals of the respective states of 2 and 4 suggest different rates and sites for the reaction with nucleophiles. For the first time, the pyran 4 has been generated and trapped. As a precursor for 4, 3-bromo-4H-pyran (9) was chosen, the synthesis of which was achieved on two routes from 4H-pyran. The treatment of 9 with potassium tert-butoxide (KOt-Bu)/18-crown-6 gave 4-tert butoxy-4H-pyran as the only discernible product, whether styrene or furan was present, indicating the interception of 4 by KOt-Bu. Finally, the disagreement between the experiment and the theory concerning the heat of formation and the electronic nature of the isobenzene 2 is resolved by demonstrating that the experimental data can provide only an upper limit of the DeltaH(f) degrees value. PMID- 11782182 TI - Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by (2)H NMR and molecular dynamics simulations. AB - Polyunsaturated phospholipids are known to be important with regard to the biological functions of essential fatty acids, for example, involving neural tissues such as the brain and retina. Here we have employed two complementary structural methods for the study of polyunsaturated bilayer lipids, viz. deuterium ((2)H) NMR spectroscopy and molecular dynamics (MD) computer simulations. Our research constitutes one of the first applications of all-atom MD simulations to polyunsaturated lipids containing docosahexaenoic acid (DHA; 22:6 cis-Delta(4,7,10,13,16,19)). Structural features of the highly unsaturated, mixed-chain phospholipid, 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3 phosphocholine (PDPC), have been studied in the liquid-crystalline (L(alpha)) state and compared to the less unsaturated homolog, 1-palmitoyl-2-oleoyl-sn glycero-3-phosphocholine (POPC). The (2)H NMR spectra of polyunsaturated bilayers are dramatically different from those of less unsaturated phospholipid bilayers. We show how use of MD simulations can aid in interpreting the complex (2)H NMR spectra of polyunsaturated bilayers, in conjunction with electron density profiles determined from small-angle X-ray diffraction studies. This work clearly demonstrates preferred helical and angle-iron conformations of the polyunsaturated chains in liquid-crystalline bilayers, which favor chain extension while maintaining bilayer flexibility. The presence of relatively long, extended fatty acyl chains may be important for solvating the hydrophobic surfaces of integral membrane proteins, such as rhodopsin. In addition, the polyallylic DHA chains have a tendency to adopt back-bended (hairpin-like) structures, which increase the interfacial area per lipid. Finally, the material properties have been analyzed in terms of the response of the bilayer to mechanical stress. Simulated bilayers of phospholipids containing docosahexaenoic acid were less sensitive to the applied surface tension than were saturated phospholipids, possibly implying a decrease in membrane elasticity (area elastic modulus, bending rigidity). The above features distinguish DHA-containing lipids from saturated or monounsaturated lipids and may be important for their biological modes of action. PMID- 11782183 TI - Formation of a stable surface oxametallacycle that produces ethylene oxide. AB - Temperature programmed desorption, high-resolution electron energy loss spectroscopy (HREELS), and density functional theory (DFT) were used to investigate the adsorption and reaction of ethylene oxide (EO) on the Ag(111) surface. When EO is dosed onto Ag(111) at 140 K it adsorbs molecularly, desorbing without reaction at approximately 200 K. On the other hand, when EO is dosed at 250 K, the ring-opening of EO is activated, and a stable surface intermediate is formed. This intermediate reacts at 300 K to re-form EO plus a few other products. HREELS and DFT studies suggest that this stable intermediate is a surface oxametallacycle. Moreover, the activation energies observed for the reaction of the oxametallacycle to form EO are in an excellent agreement with the values reported for the steady-state ethylene epoxidation process. This work represents the first demonstration of surface oxametallacycle ring-closure to form EO. Comparison of the spectroscopic results obtained from silver single crystals and supported catalysts strongly suggests that oxametallacycles are important intermediates in silver-catalyzed ethylene epoxidation. PMID- 11782184 TI - Polyunsaturated fatty acids in lipid bilayers: intrinsic and environmental contributions to their unique physical properties. AB - Polyunsaturated lipids are an essential component of biological membranes, influencing order and dynamics of lipids, protein-lipid interaction, and membrane transport properties. To gain an atomic level picture of the impact of polyunsaturation on membrane properties, quantum mechanical (QM) and empirical force field based calculations have been undertaken. The QM calculations of the torsional energy surface for rotation about vinyl-methylene bonds reveal low barriers to rotation, indicating an intrinsic propensity toward flexibility. Based on QM and experimental data, empirical force field parameters were developed for polyunsaturated lipids and applied in a 16 ns molecular dynamics (MD) simulation of a 1-stearoyl-2-docosahexaenoyl-sn-glyerco-3-phosphocholine (SDPC) lipid bilayer. The simulation results are in good agreement with experimental data, suggesting an unusually high degree of conformational flexibility of polyunsaturated hydrocarbon chains in membranes. The detailed analysis of chain conformation and dynamics by simulations is aiding the interpretation of experimental data and is useful for understanding the unique role of polyunsaturated lipids in biological membranes. The complete force field is included as Supporting Information and is available from http://www.pharmacy.umaryland.edu/faculty/amackere/research.html. PMID- 11782185 TI - An ab initio study of amide proton shift tensor dependence on local protein structure. AB - Ab initio shielding tensor calculations were carried out on residues in human ubiquitin. Reported experimental data on isotropic and anisotropic components of the amide proton chemical shifts were used as benchmarks to test the validity of the chosen basis sets as well as methods in structure optimization and shielding calculations. The best agreement with the experimental values was observed when the 6-311**G and 6-311++G(2d,2p) basis sets were used to optimize the structure and to calculate the shielding tensor, respectively. The same method was employed in subsequent model calculations to characterize the dependence of amide proton shielding to the local structure. Both the isotropic and the anisotropic components of the symmetric tensor were found to depend very strongly on the hydrogen bond length. A weaker dependence can also be observed for the hydrogen bond angle. Antisymmetric tensor elements were found to be relatively small. This study permits separation of various local structure contributions to the amide proton shielding tensor that complements scarce experimental data. PMID- 11782186 TI - Dynamics of the gas-phase reactions of chloride ion with fluoromethane: high excess translational activation energy for an endothermic S(N)2 reaction. AB - Guided ion beam tandem mass spectrometry techniques are used to examine the competing product channels in the reaction of Cl(-) with CH(3)F in the center-of mass collision energy range 0.05-27 eV. Four anionic reaction products are detected: F(-), CH(2)Cl(-), FCl(-), and CHCl(-). The endothermic S(N)2 reaction Cl(-) + CH(3)F --> CH(3)Cl + F(-) has an energy threshold of E(0) = 181 +/- 14 kJ/mol, exhibiting a 52 +/- 16 kJ/mol effective barrier in excess of the reaction endothermicity. The potential energy of the S(N)2 transition state is well below the energy of the products. Dynamical impedances to the activation of the S(N)2 reaction are discussed, including angular momentum constraints, orientational effects, and the inefficiency of translational energy in promoting the reaction. The fluorine abstraction reaction to form CH(3) + FCl(-) exhibits a 146 +/- 33 kJ/mol effective barrier above the reaction endothermicity. Direct proton transfer to form HCl is highly inefficient, but HF elimination is observed above 268 +/- 95 kJ/mol. Potential energy surfaces for the reactions are calculated using the CCSD(T)/aug-cc-pVDZ and HF/6-31+G(d) methods and used to interpret the dynamics. PMID- 11782187 TI - Experimental and theoretical studies on the reaction of H(2) with NiO: role of O vacancies and mechanism for oxide reduction. AB - Reduction of an oxide in hydrogen is a method frequently employed in the preparation of active catalysts and electronic devices. Synchrotron-based time resolved X-ray diffraction (XRD), X-ray absorption fine structure (NEXAFS/EXAFS), photoemission, and first-principles density-functional (DF) slab calculations were used to study the reaction of H(2) with nickel oxide. In experiments with a NiO(100) crystal and NiO powders, oxide reduction is observed at atmospheric pressures and elevated temperatures (250-350 degrees C), but only after an induction period. The results of in situ time-resolved XRD and NEXAFS/EXAFS show a direct NiO-->Ni transformation without accumulation of any intermediate phase. During the induction period, surface defect sites are created that provide a high efficiency for the dissociation of H(2). A perfect NiO(100) surface, the most common face of nickel oxide, exhibits a negligible reactivity toward H(2). The presence of O vacancies leads to an increase in the adsorption energy of H(2) and substantially lowers the energy barrier associated with the cleavage of the H-H bond. At the same time, adsorbed hydrogen can induce the migration of O vacancies from the bulk to the surface of the oxide. A correlation is observed between the concentration of vacancies in the NiO lattice and the rate of oxide reduction. These results illustrate the complex role played by O vacancies in the mechanism for reduction of an oxide. The kinetic models frequently used to explain the existence of an induction time during the reduction process can be important, but a more relevant aspect is the initial production of active sites for the rapid dissociation of H(2). PMID- 11782188 TI - An experimental and computational evaluation of the energetics of the isomeric methoxyphenylcarbenes generated in carbon atom reactions. AB - Carbon atom reactions with anisole and methoxybenzaldehyde demonstrate the reversible ring expansion of methoxyphenylcarbene (CH(3)O-C(6)H(4)-C-H). Trapping with HBF(4) yields the methoxytropylium ion, analogous to the well-known reactions of phenylcarbene. For instance, in the reaction of carbon atom with p methoxybenzaldehyde, which proceeds by deoxygenation of the carbonyl group and formation of the corresponding arylcarbene, the products formed are methoxytropylium fluoroborate, p-methoxytoluene and m-methoxytoluene in yields of 69.4, 7.6, and 22.9%, respectively. Gas-phase density functional theory calculations were also carried out. The observed product yields from the uniquely generated p- and m-methoxyphenylcarbenes are in good agreement with the calculations. In the case of o-methoxyphenylcarbene, however, the calculations indicate that formation of dihydrobenzofuran is the most facile rearrangement on the ground-state singlet surface. In contrast, ring expansion is observed to be the major reaction path experimentally. The exothermicity of the deoxygenation step for carbon atom reaction with methoxybenzaldehyde ( approximately 100 kcal/mol) can allow for an excited singlet state to be formed initially. This excited singlet state of the methoxyphenylcarbene will resemble open-shell phenylnitrene, which is known to undergo ring expansion much more readily than phenylcarbene. On the basis of this analogy, we reconcile the difference in reactivity of the arylcarbene predicted by density functional theory calculations with the reactivity observed experimentally. PMID- 11782189 TI - Rapid, low cost thin-layer chromatographic screening method for the detection of ochratoxin A in green coffee at a control level of 10 microg/kg. AB - A thin-layer chromatographic (TLC) screening method was developed for the detection of ochratoxin A (OTA) in green coffee at a control level of 10 microg/kg. The method is based on extraction of OTA with a mixture of phosphoric acid and dichloromethane, purification by liquid-liquid partition into sodium hydrogen carbonate, separation by normal-phase TLC, and detection by visual estimation of fluorescence intensity under a UV lamp at 366 nm. The method was validated by performing replicate analyses of uncontaminated green coffee material spiked at 3 different levels of OTA (5, 10, and 20 microg/kg), and also by comparing results obtained on a series of test trial green coffees naturally contaminated with OTA (range 0.2 to 136.7 microg/kg) with those measured by a quantitative immunoaffinity/HPLC method. The agreement between the two methods was excellent, and neither false positive nor false negative results were recorded. This screening method is rapid, simple, robust, and very cheap, which makes it particularly well adapted for implementation in coffee-producing countries. PMID- 11782190 TI - Using a modified ferrous oxidation-xylenol orange (FOX) assay for detection of lipid hydroperoxides in plant tissue. AB - The ferrous oxidation-xylenol orange (FOX) assay was adapted for quantifying lipid hydroperoxides (LOOHs) in plant extracts. Excised pieces of several fruit and vegetable species were exposed to 83 kJ m(-2) day(-1) of biologically effective ultraviolet B irradiance (UV-B(BE)) for 10-12 days to induce cellular oxidation. The LOOH and thiobarbituric acid reactive substance (TBARS) concentrations of these plant tissues were assessed with the FOX and iodometric assays for the former and a modified TBARS assay for the latter. There was generally good agreement between the FOX and iodometric methods both prior to and following the UV exposure. However, the iodometric assay appeared to have some difficulty in consistently quantifying lower LOOH levels (<11 microM), whereas the FOX assay measured LOOH concentrations as low as 5 microM. All tissues exhibited UV-induced increases in TBARS, indicating a marked degree of cellular oxidation in the exposed tissue segments. Compared with the iodometric assay, the FOX method consistently generated less variable LOOH values. The presence of authentic linoleic acid-OOHs in spiked avocado and spinach samples (11 microM) was identified with liquid chromatography-mass spectrometry techniques, which validated corresponding FOX assay results. The FOX method is inexpensive, is not sensitive to ambient O2 or light levels, and can rapidly generate LOOH measurements. The physiological value of the FOX assay resides in its ability to measure initial rather than more advanced fatty acid oxidation; hence, early membrane-associated stress events in plant tissue can be detected. PMID- 11782191 TI - Studies on the constituents of a Brazilian folk infusion. Isolation and structure elucidation of new triterpene saponins from Ilex amara leaves. AB - The isolation of three new triterpene saponins 3beta-O-beta-D-glucopyranosyl-(1- >3)-alpha-L-2-O-acetylarabinopyranosylolean-12-en-28-oic acid 28-O-beta-D glucopyranosyl ester (2), 3beta-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-O arabinopyranosylurs-12-en-28-oic acid (3), and 3beta-O-beta-D-glucopyranosyl-(1- >2)-beta-D-O-galactopyranosylurs-12-en-28-oic acid (4) together with five known saponins and one flavonoid glycoside from the aqueous infusion of Ilex amara (Vellozo) Loes. leaves is reported. All structures were elucidated by spectroscopic methods, including the concerted application of one-dimensional (1H, TOCSY, 13C, and 13C DEPT NMR) and two-dimensional NMR techniques (DQF-COSY, HSQC, and HMBC). PMID- 11782192 TI - Factors affecting the resolution of dl-menthol by immobilized lipase-catalyzed esterification in organic solvent. AB - Among 10 lipases tested, Candida rugosa lipase exhibited the best ability to catalyze the resolution of dl-menthol in organic solvent. The lipase was immobilized on different carriers, and the experiment was carried out with different acyl donors. The high yield and optical purity of the product were achieved in cyclohexane with valeric acid as acyl donor using C. rugosa lipase immobilized on DEAE-Sephadex A-25. The conversion of dl-menthol depended on the water content of immobilized lipase and on the pH of the aqueous solution from which lipase was immobilized. The operational stability of the DEAE-Sephadex A-25 immobilized lipase in catalysis of the esterification reaction showed that >85% activity remained after 34 days of repeated use. The resolution of racemic menthol in organic medium catalyzed by immobilized C. rugosa lipase-catalyzed esterification is very convenient, and it represents a significant improvement in the use of enzyme for the preparative production of optically active menthol. This process is readily applicable to large-scale preparation. PMID- 11782193 TI - Arabinoxylan-lipids-based edible films and coatings. 2. Influence of sucroester nature on the emulsion structure and film properties. AB - This work is a contribution to better knowledge of the influence of the structure of films on their functional properties obtained from emulsions based on arabinoxylans, hydrogenated palm kernel oil (HPKO), and emulsifiers. The sucroesters (emulsifiers) have a great effect on the stabilization of the emulsified film structure containing arabinoxylans and hydrogenated palm kernel oil. They improve the moisture barrier properties. Several sucroesters having different esterification degrees were tested. Both lipophilic (90% of di and tri ester) and hydrophilic (70% of mono-ester) sucrose esters can ensure the stability of the emulsion used to form the film, especially during preparation and drying. These emulsifiers confer good moisture barrier properties to emulsified films. PMID- 11782194 TI - Changes in cell wall pectins accompanying tomato (Lycopersicon esculentum Mill.) paste manufacture. AB - The texture of processed tomato products is influenced by the size and solubility characteristics of soluble and particle-bound cell wall polysaccharides they contain. The acidic (pectin) polysaccharides are important contributors to texture because of their gel-forming capability and the fact that they can form aggregates. The present work describes the pectins in ripe tomato fruits and then follows changes in several classes of pectins as the fruits are subjected to hot break and the juice is subsequently concentrated to a 30 degrees Brix paste. Continued processing leads to progressive solubilization and depolymerization of polysaccharides so that the ionically and covalently bound materials that are the major pectin classes of ripe fruit are substantially reduced in amount with the concomitant increase in the more soluble water-soluble pectins of the paste product. Juice content of soluble solids ( degrees Brix) rose steadily as water content was reduced during processing. Juice content of polymeric uronic acids (i.e., pectin) also rose with concentration, but to a lesser degree than the increase in soluble solids. This indicates that processing leads to almost complete pectin depolymerization and/or the alteration of uronic acid structures so that this assay could no longer detect them. It was concluded that reductions in heat input during processing would lead to pastes with greater pectin integrity and enhanced textural characteristics. PMID- 11782195 TI - Is the application of carbendazim harmful to healthy plants? Evidence of weak phytotoxicity in tobacco. AB - To understand the phytotoxic effects that certain bezimidazole fungicides exert on plant growth, the aim of the present study was to determine the effect of the fungicide carbendazim, on foliar biomass, pigment content, and nutrient levels in tobacco plants (Nicotiana tabacum L. cv. Tennessee 86). The fungicide applied was carbendazim with a purity of 100%, at three different rates: 1.3 mM (carb1), 2.6 mM (the recommended concentration, carb2), and 5.2 mM (carb3). The control treatment was without carbendazim. The application of dosages of this fungicide lower than recommended (1.3 mM) resulted, on the one hand, in greater dry weight and, on the other, higher carotenoid concentrations, as well as higher N and K concentrations with respect to control. On the contrary, the application of the carbendazim dosage higher than recommended (5.2 mM) caused a decrease in dry weight and in all of the foliar pigments, as well as all of the nutrients, with respect to the other dosages and control. These results appear to indicate that besides its direct antibiotic action against pathogens, the effects of this fungicide in plants could be dangerous, especially at higher dosages. Nevertheless, the negative effects of carbendazim can be avoided by reducing the amount applied in current agriculture. PMID- 11782196 TI - Nature of impurities in fertilizers containing EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+) chelates. AB - Iron chelates derived from ethylenediaminedi(o-hydroxyphenylacetic) acid (EDDHA), ethylenediaminedi(o-hydroxy-p-methylphenylacetic) acid (EDDHMA), ethylenediaminedi(2-hydroxy-5-sulfophenylacetic) acid (EDDHSA), and ethylenediaminedi(5-carboxy-2-hydroxyphenylacetic) acid (EDDCHA) are remarkably efficient in correcting iron chlorosis in plants growing in alkaline soils. This work reports the determination of impurities in commercial samples of fertilizers containing EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+). The active components (EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+)) were separated easily from other compounds present in the fertilizers by HPLC. Comparison of the retention times and the UV-visible spectra of the peaks obtained from commercial EDDHSA/Fe(3+) and EDDCHA/Fe(3+) samples with those of standard solutions showed that unreacted starting materials (p-hydroxybenzenesulfonic acid and p hydroxybenzoic acid, respectively) were always present in the commercial products. 1D and 2D NMR experiments showed that commercial fertilizers based on EDDHMA/Fe(3+) contained impurities having structures tentatively assigned to iron chelates of two isomers of EDDHMA. These findings suggest that current production processes of iron chelates used in agriculture need to be improved. PMID- 11782198 TI - Aroma extracts from oyster Crassostrea gigas: comparison of two extraction methods. AB - The study of the aroma of oysters is of great economic interest in France because it enables their organoleptic quality to be verified. The aim of this study is to optimize the extraction methods of the volatile compounds of oysters Crassostrea gigas in order to obtain an extract with an odor as close as possible to that of the original oysters'. Oyster aroma is rarely studied, and its sensory profile has not been investigated to date. Two extraction methods were studied: vacuum hydrodistillation carried out at 20 degrees C with noncrushed oyster using ultrapure water and dynamic headspace carried out using noncrushed oyster during a 30 min purge. They were compared with regard to their sensory characteristics by a panel of seven judges, all trained in seafood aroma recognition. This study has shown that vacuum hydrodistillation is the better method to obtain an extract closest in aroma to the oyster reference. PMID- 11782197 TI - Adsorption of imidazolinone herbicides on smectite-humic acid and smectite ferrihydrite associations. AB - Adsorption of imazapyr (IMZ), imazethapyr (IMZT), and imazaquin (IMZQ) was studied on two smectite-humic acid and two smectite-ferrihydrite binary systems prepared by treating a Wyoming smectite with a humic acid extracted from soil (4 and 8% w/w of the smectite) and with just-precipitated synthetic ferrihydrite (8 and 16% w/w of the smectite). Adsorption of the three herbicides on the smectite was not measurable at pH >4.5, presumably because of negative charges on the surface of the smectite. Adsorption on the smectite-humic acid systems was also not measurable, presumably because of negative charges on the surface, despite the high affinity of the three herbicides for humic acid, the adsorption order of which was IMZ < IMZT << IMZQ. Adsorption decreased in the order IMZ < IMZT < IMZQ on the smectite-ferrihydrite systems and IMZQ < IMZT < IMZ on ferrihydrite, although here the differences were small. These results show that even though pure smectite cannot adsorb herbicides, it modifies the adsorption capacity of ferrihydrite. The mutual interaction of active phases such as humic acid, ferrihydrite, and smectite alters the characteristics of the resulting surface and hence the adsorption process. Investigations of herbicide adsorption have been seen to produce more reliable results if conducted on polyphasic systems rather than on single soil components. PMID- 11782199 TI - Volatile flavor components of stored nonfat dry milk. AB - Nonfat dry milk (NDM) is widely used both as an ingredient in other preparations and for direct consumption. Flavor quality of NDM is a critical parameter because it can directly impact final product quality. Flavors can be formed in NDM during subsequent storage. Identification of compounds responsible for storage-induced flavors is necessary to correlate sensory quality with potential sources of the flavors. Six NDM samples were selected for volatile flavor analysis based on sensory analysis and storage time. Volatile components were extracted by direct solvent extraction/high vacuum distillation. Volatile extracts were separated into neutral/basic and acidic fractions and analyzed by gas chromatography olfactometry (GCO) and aroma extract dilution analysis (AEDA). A variety of aldehydes, ketones, and free fatty acids were responsible for generation of flavors in stored NDM. The following compounds exhibited high aroma impact by AEDA: 3-(methylthio)propanal (boiled potato); o-aminoacetophenone (corn tortilla); 2,5-dimethyl-4-hydroxy-3(2H)-furanone and 2-methyl-3-hydroxy-4H-pyran 4-one (burnt sugar); butanoic acid (cheesy); pentanoic acid (sweaty); acetic and hexanoic acids (sour/vinegar); octanoic, decanoic, and dodecanoic acids (waxy); p cresol (cowy/barny); 3-methylindole (fecal); dimethyl trisulfide (cabbage); (E,E) 2,4-decadienal (fried/fatty); furfuryl alcohol (rubber/vitamin); phenylacetic acid (rose-like); and 1-octen-3-one (mushroom). PMID- 11782200 TI - Improvement of the bitter taste of amino acids through the transpeptidation reaction of bacterial gamma-glutamyltranspeptidase. AB - The tastes of several bitter amino acids and their gamma-glutamyl derivatives were compared. The bitterness of Phe, Val, Leu, and His was reduced, sourness was produced, and preferences were increased by gamma-glutamylization. Because the effect of gamma-glutamylization of bitter amino acids was most obvious for Phe, which is an atypical bitter amino acid, an enzymatic method for the synthesis of gamma-glutamylphenylalanine (gamma-Glu-Phe) involving bacterial gamma glutamyltranspeptidase was developed. The optimum reaction conditions were 200 mM Gln, 200 mM Phe, and 0.5 unit/mL GGT, pH 10.4. After 1.5-h of incubation at 37 degrees C, 140 mM gamma-Glu-Phe was obtained, the yield being 70%. gamma-Glu-Phe was purified on a Dowex 1x8 column and then identified by NMR. PMID- 11782201 TI - Chemical interactions between odor-active thiols and melanoidins involved in the aroma staling of coffee beverages. AB - Comparative aroma dilution analyses of the headspaces of aqueous solutions containing either the total volatiles isolated from a fresh coffee brew, or these volatiles remixed with the melanoidins isolated from coffee brew, revealed a drastic decrease in the concentrations of the odorous thiols 2-furfurylthiol, 3 methyl-2-butenthiol, 3-mercapto-3-methylbutyl formate, 2-methyl-3-furanthiol, and methanethiol when melanoidins were present. Among these thiols, 2-furfurylthiol was affected the most: e.g., its concentration decreased by a factor of 16 upon addition of melanoidins. This was accompanied by a decrease in the overall roasty sulfury aroma. Quantitations performed by means of stable isotope dilution assays confirmed the rapid loss of all thiols with increasing time while keeping the coffee brew warm in a thermos flask. Using [2H2]-2-furfurylthiol as an example, [2H]-NMR and LC/MS spectroscopy gave strong evidence that thiols are covalently bound to the coffee melanoidins via Maillard-derived pyrazinium compounds formed as oxidation products of 1,4-bis-(5-amino-5-carboxy-1-pentyl)pyrazinium radical cations (CROSSPY). Using synthetic 1,4-diethyl diquaternary pyrazinium ions and 2 furfurylthiol, it was shown that 2-(2-furyl)methylthio-1,4-dihydro-pyrazines, bis[2-(2-furyl)methylthio]-1,4-dihydro-pyrazines, and 2-(2-furyl)methylthio hydroxy-1,4-dihydro-pyrazines were formed as the primary reaction products. Similar results were obtained for models in which either 1,4-diethyl diquaternary pyrazinium ions were substituted by Nalpha-acetyl-L-lysine/glycolaldehyde, or the 2-furfurylthiol by 2-methyl-3-furanthiol and 3-mercapto-3-methylbutyl formate. On the basis of these results it can be concluded that the CROSSPY-derived pyrazinium intermediates are involved in the rapid covalent binding of odorous thiols to melanoidins, and, consequently, are responsible for the decrease in the sulfury-roasty odor quality observed shortly after preparation of the coffee brew. PMID- 11782202 TI - pH-dependent interaction of fumonisin B1 with cholesterol: physicochemical and molecular modeling studies at the air-water interface. AB - Langmuir film balance technology was used to study the interaction between the mycotoxin fumonisin B1 (FB1) and cholesterol. FB1 was added in the aqueous subphase underneath a monomolecular film of cholesterol, and the interaction was measured as an increase in the surface pressure of the film. Above pH 9, a strong inhibition of the reaction was observed. Similar results were obtained with the bile salt sodium taurocholate. The FB1-cholesterol complex was reinforced by NaCl but was destabilized by NaF, a salt known to break hydrogen bonds. These data suggest that the molecular association between FB1 and cholesterol involves both hydrophobic interactions and a hydrogen bond between the NH3(+) group of FB1 and the OH group of cholesterol. Molecular mechanics simulations of the FB1 cholesterol complex were consistent with this hypothesis. These data may shed some light on the mechanisms involved in the intestinal absorption of FB1 and its biliary excretion. PMID- 11782203 TI - Genotypic variation in fatty acid content of blackcurrant seeds. AB - The fatty acid composition and total fatty acid content of seeds from 36 blackcurrant genotypes developed at the Scottish Crop Research Institute were examined. A rapid small-scale procedure, involving homogenization of seeds in toluene followed by sodium methoxide transesterification and gas chromatography, was used. There was considerable variation between genotypes. The gamma-linolenic acid content generally varied from 11 to 19% of the total fatty acids, but three genotypes had higher values of 22-24%, levels previously not reported for blackcurrant seed and similar to those for borage seed. Other nutritionally important fatty acids, stearidonic acid and alpha-linolenic acid, varied from 2 to 4% and 10-19%, respectively. The mean total fatty acid contents ranged from 14 to 23% of the seed, but repeatability was poor. The results are discussed. Blackcurrant seeds are mainly byproducts from juice production, and the study shows the potential for developing blackcurrant genotypes with optimal added value. PMID- 11782204 TI - Pasting properties of gamma-irradiated rice starches as affected by pH. AB - Changes in the viscosity properties of gamma-irradiated rice starches (from 1 to 25% amylose content) from four genotypes (JY293, Jiayu 293; XS, Xiushui; ZF504, Zhefu 504; and ZXN, Zaoxiannuo) during pasting in water (pH 7) or in different pH solutions were studied using a rapid visco analyzer. Peak viscosity (PV) of all native rice starches was little affected at pH 4 and 10, while hot paste viscosity (HPV) and cool paste (final) viscosity (CPV) were generally lower at pH 4 and higher at pH 10 as compared with that at pH 7. The PV, HPV, and CPV of gamma-irradiated starches were higher at pH 4 and lower at pH 10 than pH 7. All viscosity characteristics of native rice starches were reduced in stronger alkali (pH 11.5) or acidic (pH 2.5) solutions. However, the gamma-irradiated starches were substantially higher at pH 2.5 but lower at pH 11.5, indicating that the effect of irradiation was highly pH dependent. The swelling volume of irradiated ZF504 and JY293 starch at all irradiation levels was higher at pH 4 than pH 7, while the values were lowest at pH 2.5. The irradiated ZXN and XS starches had higher swelling volumes at pH 4 and pH 2.5 than pH 7. Differential scanning calorimetry analysis showed that gamma-irradiation caused progressively lower gelatinization peak temperature (T(p)) and higher gelatinization range (T(r)) at pH 7. T(p) was higher and T(r) was lower at a much stronger acidic condition (pH 1) for both native and irradiated starches. The possibility of using viscosity changes in low pH for the detection of irradiated starch was discussed. PMID- 11782205 TI - Pectic methyl and nonmethyl esters in potato cell walls. AB - Because pectins are released from potatoes and other plants under conditions that cleave ester linkages, it has been suggested that there are other galaturonoyl ester cross-links between pectin chains in addition to the known non-cross linking methyl esters. A microscale titration method and a copper binding method were developed for the measurement of total polymer carboxyl (essentially pectic) ester content in potato cell walls. Relative to the uronic acid content of the cell walls, the degree of total esterification was 57-58%. Comparison with levels of methanol released on ester hydrolysis allowed nonmethyl uronoyl esters to be estimated to be 14-15% relative to total uronic acid. The possibility of nonmethyl-esterified linkages being formed in potato cell walls by a side reaction catalyzed by pectin methyl esterase (PME) was investigated, but no increase in nonmethyl-esterified pectin was observed under conditions where pectin was being effectively de-esterified by endogenous PME activity. PMID- 11782206 TI - Nutritional and physicochemical characteristics of dietary fiber enriched pasta. AB - The relationship between pasta texture and physicostructural characteristics was determined in relation to potential starch degradation and subsequent glucose release. Pastas with added soluble and insoluble dietary fiber ingredients were evaluated in relation to biochemical composition, cooking properties, and textural characteristics. Results show that both the type and amount of added fiber influence the overall quality of both raw and cooked pasta. Glucose release may be significantly reduced by the addition of soluble dietary fiber. PMID- 11782207 TI - Monoacylglycerol from Punica granatum seed oil. AB - The seeds of Punica granatum, known as hap roman in the Arabian Peninsula, are commonly eaten as a dessert. As part of an ongoing project to find nonnutritional natural products which have health benefits, or that can be exploited to protect crops, the chloroform-soluble extract of the fermented seeds of P. granatum was found to be rich in 1-O-trans,cis,trans-9,11,13-octadecatrienoyl glycerol (1). The seed oil is not lethal to brine shrimp larvae. 1-O-isopentyl-3-O-octadec-2 enoyl glycerol (2) and the known cis-9-octadecenoic, octadecanoic, and eicosanoic acids were also detected in small amounts in the seed oil by LC and MS. The structure of 1 was determined from NMR and MS spectral data. PMID- 11782208 TI - Characterization of starch from tubers of yam bean (Pachyrhizus ahipa). AB - Detailed studies of the starch present in tubers of six accessions of Pachyrhizus ahipa (ahipa) have been carried out using starches from tubers of P. erosus (Mexican yam bean) and seeds of ahipa and wheat for comparison. Starch accounted for 56-58% of the tuber dry weight with granules occurring in a range of geometric forms and in sizes from below 5 microm to about 35 microm (mean about 10 microm in all accessions except two). The amylose content ranged from 11.6 to 16.8% compared with 16.9% in P. erosus tubers and over 23% in the seed starches. X- ray diffraction analysis showed A-type or C(A)-type diffraction patterns. The chain-length distribution of the amylopectin after enzyme debranching showed a peak at DP11 similar to that of wheat starch, but had a less marked shoulder at DP 21-22 and contained a higher proportion of longer chains. Differential scanning calorimitry showed an endothermic peak corresponding to gelatinization with T(max) ranging from 59 to 63 degrees C, which was similar to the T(max) of wheat (about 64 degrees C). The composition of the ahipa starch may mean that it is suitable for food applications that require low amylose content and low retrogradation after processing. PMID- 11782209 TI - Extraction and purification of squalene from amaranthus grain. AB - Grain amaranth has been suggested as an alternative to marine animals as a natural source of squalene. Oil contents, squalene contents, and fatty acid profiles were determined in 11 genotypes of four grain amaranth species. Although the oil contents of grain amaranth were low (from 5.1% in Amaranthus tricolor to 7.7% in Amaranthus cruentus) as compared to other oil-containing grains, high concentrations of squalene were found in total lipids, ranging from 3.6% in Amaranthus hypochondriacus to 6.1% in A. tricolor. The major fatty acids in Amaranthus oil consisted of palmitic acid (19.1-23.4%), oleic acid (18.7-38.9%), and linoleic acid (36.7-55.9%). A high degree of unsaturation was observed in Amaranthus oils, with S/U ratios of 0.26-0.32. A method to isolate and purify the squalene from Amaranthus oil was developed. After the saponification of K112, the squalene content increased from 4.2% in the crude oil to 43.3% in the unsaponifiables by the removal of the saponifiables. The unsaponifiables were fractionated by silica gel column chromatography to get highly purified squalene. The squalene purity in certain fractions was as high as 98%. Combining the fractions rich in squalene gave a 94% squalene concentrate, with a yield of 90%. The structure of squalene in the purified sample was confirmed by comparison of its ultraviolet spectrum with a standard and from its nuclear magnetic resonance spectra. PMID- 11782210 TI - Antioxidant activity of polyphenols in carob pods. AB - We extracted polyphenols from carob (Ceratonia siliqua L.) pods, and evaluated the in vitro antioxidant activity of the crude polyphenol fraction (CPP). The total polyphenol content in CPP determined by the Folin-Ciocalteu method was 19.2%. The condensed tannin content determined by the vanillin and proanthocyanidin assay systems was 4.37% and 1.36%, respectively. beta-Carotene bleaching, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, inhibition of lipid peroxidation by the erythrocyte ghost, and microsomal assay systems were used to evaluate the antioxidant activity. CPP showed a stronger inhibitory effect against the discoloration of beta-carotene than other polyphenol compounds such as catechins and procyanidins. CPP had weaker antioxidant activity in the DPPH free radical scavenging, the erythrocyte ghost, and microsomal systems than authentic polyphenol compounds at the same concentrations. The activity adjusted by the polyphenol concentration was, however, comparable to that of authentic polyphenol compounds. Considering most carob pods are discarded and not effectively utilized at present, these results suggested that carob pods could be utilized as a functional food or food ingredient. PMID- 11782211 TI - Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. AB - The objective of this study was to compare the modulatory effect of garlic oil and its three organosulfur compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), on rat hepatic detoxification enzyme activity, and protein and mRNA expression. Rats were orally administered garlic oil (80 or 200 mg/kg bw), DAS (20 or 80 mg/kg bw), DADS (80 mg/kg bw), or DATS (70 mg/kg bw) three times a week for 6 weeks. Control rats received corn oil. According to the results, garlic oil and DAS in dosages of 200 and 80 mg/kg bw, respectively, significantly increased pentoxyresorufin O-dealkylase (PROD) activity as compared with the that of the control rats (P < 0.05). In contrast, N nitrosodimethylamine demethylase activity in rats that received DADS and DATS was significantly lower than that in the control rats (P < 0.05). Ethoxyresorufin O deethylase and erythromycin demethylase activities were not influenced by garlic oil, DAS, DADS, or DATS. To the phase II enzyme, garlic oil, DADS, and DATS significantly increased the glutathione S-transferase (GST) activity toward ethacrynic aicd (P < 0.05). Immunoblot assay showed that the protein contents of cytochrome P450 1A1, 2B1, and 3A1 were increased by garlic oil and each of three allyl sulfides, and the change among the allyl sulfides was in the order of DAS > DADS > DATS. The placental form of GST (PGST) level was also increased by garlic oil and the three allyl sulfides, but the increase among the allyl sulfides was DATS congruent with DADS > DAS. P450 2E1, however, was suppressed by each garlic component. Northern blot results indicated that the changes in P450 1A1, 2B1, 3A1, and PGST mRNA levels by garlic components were similar to those noted in the protein levels. These results indicate that the modulatory effect of garlic oil on hepatic drug-metabolizing enzymes can be attributed to its three major allyl sulfide components DAS, DADS, and DATS. These three allyl sulfides vary in modulatory activity, and this variation is related to the number of sulfur atoms in the molecule. PMID- 11782212 TI - Biological activity of alpha-galactoside preparations from Lupinus angustifolius L. and Pisum sativum L. seeds. AB - Biological activity tests were performed on alpha-galactoside preparations obtained from Lupinus angustifolius L. cv. Mirela (alkaloid-rich) and Pisum sativum L. cv. Opal seeds. The studies included the following tests: acute toxicity, cytotoxic test, delayed type hypersensitivity (DTH), plaque-forming cell number (IgM-PFC), and influence on the growth of bifidobacteria and coliform presence in rat colon. Results of these studies showed that alpha-galactosides from lupin and pea seeds were essentially nontoxic. Their acute toxicity (LD(50)) in mice was >4000 mg kg(-1) of body weight. alpha-galactoside preparations were not cytotoxic for mouse thymocytes in vitro. The in vitro test shows that oligosaccharides from lupin and pea are utilized by selected beneficial colon bacterium strains. The in vivo experiment demonstrated that alpha-galactosides from legume significantly influenced the growth of bifidobacteria in rats colon. Simultaneously, the decrease of the coliform presence was observed. The chemical composition of the tested preparations had no significant effect on their biological activity. PMID- 11782213 TI - Inhibition of iron uptake by phytic acid, tannic acid, and ZnCl2: studies using an in vitro digestion/Caco-2 cell model. AB - The objective of this study was to document the effects of phytic acid, tannic acid, and zinc on iron uptake in an in vitro digestion/Caco-2 cell culture model. The effects of phytic acid and tannic acid on iron uptake were measured at increasing molar ratios of FeCl3 to phytic acid or tannic acid. Maximal inhibition of iron uptake by phytic acid occurred at a 1:10 ratio of Fe to phytic acid. Dialyzable Fe decreased with a low Fe to phytic acid ratio but increased with Fe:phytic acid ratios greater than 1:3 indicating that more iron was soluble at higher phytic acid levels but less available. As in human studies, heme iron was less inhibited by phytic acid than nonheme iron. Tannic acid was a more potent inhibitor of nonheme iron uptake, as maximal inhibition (97.5%) of iron uptake occurred at a ratio of 1:1 or less. The addition of ZnCl2 to the digest at ratios of 1:0.5 and 1:1 decreased iron uptake by 57 and 80%, respectively. Overall, the results agree qualitatively with studies in humans and demonstrate the relative effects of these compounds on iron uptake in this model system. This study provides key information for determining iron availability under more complex meal conditions. PMID- 11782214 TI - A novel zwitterionic anthocyanin from evergreen blackberry (Rubus laciniatus Willd.). AB - A novel zwitterionic anthocyanin was isolated from evergreen blackberry (Rubus laciniatus Willd.) and structurally characterized as cyanidin 3 dioxalylglucoside. During short-term storage in acidified methanol, methyl esterification of the carboxyl group of the terminal oxalyl unit occurred, providing additional information for structural elucidation. Until now, oxalic acid as an acyl moiety of anthocyanins has been reported only in orchid flowers (Orchidaceae) but never in fruits or in the Rosaceae. This is the first report of an anthocyanin diacylated with oxalic acid, establishing a more widespread occurrence of anthocyanins substituted with aliphatic acids than hitherto believed. PMID- 11782215 TI - Basis for a new procedure to eliminate diarrheic shellfish toxins from a contaminated matrix. AB - The natural contamination of shellfish with diarrheic shellfish toxins (DSP) has important public health implications. To avoid the economic effects of toxic episodes on shellfish farmers and the related industry, research on artificial methods alternative to the natural detoxification of shellfish is needed. Because the usual thermal processes are not efficient, alternative technologies have to be studied. Here preliminary results are presented about the lability of the DSP toxin okadaic acid in a supercritical atmosphere of carbon dioxide with acetic acid. Most of the toxin is eliminated (up to 90%), and the biological activity against its target enzyme is also severely affected (up to 70% reduction). Detoxification of contaminated shellfish requires a partial dehydration, and the detoxification yield is lower than that obtained with free toxin. Mass spectrometry experiments suggest that acetylation of the toxin molecule is not the basis of the inactivating mechanism, but a conformational change is suggested. This is the first report of the use of supercritical fluids to inactivate toxins. PMID- 11782216 TI - Screening and mass spectral confirmation of beta-lactam antibiotic residues in milk using LC-MS/MS. AB - Milk is typically screened for beta-lactam antibiotics by nonspecific methods. Although these methods are rapid and sensitive, they are not quantitative and can yield false positive findings. A sensitive and specific method for the quantitation and mass spectral confirmation of five beta-lactam and two cephalosporin antibiotics commonly or potentially used in the dairy industry is described using high-performance liquid chromatography with tandem mass spectrometry. The antibiotics studied were ampicillin, amoxicillin, penicillin G, penicillin V, cloxacillin, cephapirin, and ceftiofur. The antibiotics were extracted from milk with acetonitrile, followed by reversed-phase column cleanup. The extract was analyzed by liquid chromatography coupled with a mass spectrometer, using a water/methanol gradient containing 1% acetic acid on a C-18 reversed-phase column. Determination was by positive ion electrospray ionization and ion trap tandem mass spectrometry. Quantitation was based on the most abundant product ions from fragmentation of the protonated ion for amoxicillin, cephapirin, ampicillin, and ceftiofur and on the fragmentation of the sodium adduct for penicillin G, penicillin V, and cloxacillin. The method was validated at the U.S. FDA tolerance or safe level and at 5 or 2.5 ng/mL for these compounds in bovine milk. Theoretical method detection limits in milk based on a 10:1 signal to noise ratio were 0.2 ng/mL (ampicillin), 0.4 ng/mL (ceftiofur), 0.8 ng/mL (cephapirin), 1 ng/mL (amoxicillin and penicillin G), and 2 ng/mL (cloxacillin and penicillin V) using a nominal sample size of 5 mL. PMID- 11782217 TI - Chronic open angle glaucoma: risk factors in addition to intraocular pressure. PMID- 11782218 TI - Short wavelength automated perimetry. AB - Short Wavelength Automated Perimetry (SWAP) utilizes a blue stimulus to preferentially stimulate the blue cones and a high luminance yellow background to adapt the green and red cones and to saturate, simultaneously, the activity of the rods. This review describes the theoretical aspects of SWAP, highlights current limitations associated with the technique and discusses potential clinical applications. Compared to white-on-white (W-W) perimetry, SWAP is limited clinically by: greater variability associated with the estimation of threshold, ocular media absorption, increased examination duration and an additional learning effect. Comparative studies of SWAP and W-W perimetry have generally been undertaken on small cohorts of patients. The conclusions are frequently unconvincing due to limitations for SWAP in the delineation of abnormality and of progressive field loss. SWAP is almost certainly able to identify glaucomatous visual field loss in advance of that by W-W perimetry although the incidence of progressive field loss is similar between the two techniques. Increasing evidence suggests that functional abnormality with SWAP is preceded by structural abnormality of the optic nerve head and/or the retinal nerve fibre layer. SWAP appears to be beneficial in the detection of diabetic macular oedema and possibly in some neuro-ophthalmic disorders. PMID- 11782219 TI - Refractive error and glaucoma. AB - PURPOSE: To study the association between refractive error, glaucoma damage and IOP in a large population. METHODS: We examined 32,918 citizens of the city of Malmo, Sweden, 57-79 years of age, searching for individuals with undetected glaucoma. Refraction was measured with autorefractors. Glaucoma damage was defined as reproducible visual field defects with the Humphrey Full Threshold 24 2 program. RESULTS: Glaucoma prevalence was clearly associated with refractive state, increasing gradually with increasing myopia. This was seen both in males and females and persisted over the full age range. Glaucoma was significantly more common in myopic than in hyperopic eyes with low IOP readings (p=0.024). The overrepresentation of glaucoma in myopic eyes declined with increasing IOP and no relationship was observed in eyes with IOP > or =31 mmHg. CONCLUSION: In this large population, the prevalence of glaucoma increased with increasing myopia. The association between myopia and glaucoma was strong at lower IOP levels, and weakened gradually with increasing IOP. Our findings indicate that myopia is an important risk factor for glaucoma and particularly for normal tension glaucoma. PMID- 11782220 TI - Intraocular pressure over 24 hours after single-dose administration of latanoprost 0.005% in healthy volunteers. A randomized, double-masked, placebo controlled, cross-over single center study. AB - PURPOSE: To measure the effect on intraocular pressure (IOP) over 24 hours after single-dose administration of latanoprost 0.005%. PATIENTS AND METHODS: A randomized, double-masked placebo-controlled cross-over study was carried out. Twenty healthy volunteers were randomly assigned to receive a single drop of latanoprost 0.005% or placebo, with a 2-week wash-out period before switching therapy. After hospitalization, the IOP was measured repeatedly over 24 hours, and again after 36 and 48 hours. RESULTS: The maximum IOP reduction for latanoprost occurred 12 hours after the dose with IOP 11.7+/-0.5 mmHg (least square mean+/-standard standard error of the mean [SEM]) for latanoprost and 13.5+/-0.5 mmHg for placebo. The difference of 1.8+/-0.6 mmHg was statistically significantly in favor of latanoprost (p=0.01; ANCOVA, confidence interval (CI) [ 3.1; -0.5] mmHg). The average time to onset of action, defined as 50% of the maximal IOP reduction, was 6.0 hours for latanoprost. Latanoprost consistently reduced IOP over 24 hours after drop application with a difference in IOP reduction of 1.1+/-0.5 mmHg (p=0.03, CI [-2.1, 0.1]) at 24 hours. The corresponding IOP difference at 36 hours was 0.7+/-0.5 mmHg (p=0.20, CI [-1.7, 0.3]), and at 48 hours 0.8+/-0.5 mmHg (p=0.04, CI [-1.5, 0.0]). CONCLUSIONS: Latanoprost applied as a single dose reduced IOP over 24 hours in healthy subjects compared with placebo. The IOP reduction was still present, however, less pronounced, 48 hours after drug application. PMID- 11782221 TI - Increased aqueous humor basic fibroblast growth factor and hyaluronan levels in relation to the exfoliation syndrome and exfoliative glaucoma. AB - PURPOSE: To quantify the concentrations of basic fibroblast growth factor (bFGF) and hyaluronan (HA) in the aqueous humor of patients with the exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). METHODS: Aqueous humor bFGF and HA levels were measured in 13 patients with XFS and in 7 patients with XFG. The results were compared with those obtained from 17 healthy controls. RESULTS: Mean bFGF levels were significantly higher in the XFG patients than those in the XFS patients, which in turn were higher than the bFGF levels in the healthy individuals. Aqueous humor HA levels in both patients with the XFS and the XFG were significantly higher compared to the controls. CONCLUSION: We suggest that bFGF plays an important role in the pathogenesis of XFS and XFG, as well as in the synthesis of secreted HA, which may result in connective tissue degradation that affects the ocular anterior segment. PMID- 11782222 TI - Anterior chamber depth estimation by Scheimpflug photography. AB - PURPOSE: To obtain a model suitable for evaluation of the anterior chamber depth (ACD) maintaining capacity of viscoelastic substances--a critical parameter in cataract surgery. METHODS: ACD was estimated using an anterior segment analysis system (EAS-1000, Nidek Co Ltd, Japan). Variation was studied as an effect of batch number and eye within batch, storage, globe fixation, globe position, and repeated analyses of Scheimpflug images. RESULTS: Considerable variation in ACD was found between eyes, batches, and as a result of prolonged storage (biological factors). Different IOPs before surgery caused significant alterations in ACD after overfilling with a viscoelastic substance. No significant differences were found when the globe position was altered or when the ACD was re-estimated repeatedly from the same photograph. CONCLUSION: Differences due to biological factors are more important than methodological errors caused by the Scheimpflug instrument. To reduce these variations when viscoelastics are evaluated, all measurements should be calculated as % of ACD before surgery and the anterior chamber should be overfilled with a viscoelastic solution. PMID- 11782223 TI - The Swedish national survey of surgical excision for submacular choroidal neovascularization (CNV). AB - PURPOSE: To compare the visual outcome after surgical removal of subfoveal choroidal neovascularization (CNV) in patients younger and older than 50 years of age. METHODS: Patient records from all Swedish centers performing submacular CNV surgery were reviewed and 90 patients treated between 1992-1999 with a follow-up of 6 months or more were included. The results obtained in 49 patients aged 51-89 years (median=72 years) with neovascular disease caused by age-related macular degeneration (AMD) were compared with the outcome of 41 patients aged 6-49 years (median=36 years) with CNV secondary to non-AMD causes. The main outcome measure was the improvement or deterioration in visual acuity (standardized in logMAR units) at 6 months following surgery. Secondary endpoints were recurrent CNV and surgical complications. RESULTS: The level of preoperative visual acuity was not significantly different between younger patients with CNV associated with non-AMD and older patients with visual loss due to AMD (p=0.069). However, visual acuity at 6 months after surgery was better (p=0.0042) in younger patients (median improvement=0.19 logMAR) than in older patients (median improvement=0.0 log MAR). Marked visual improvement (>1 log MAR unit) was seen in 29% of non-AMD patients <50 years compared to 0% in the AMD group >50 years. CONCLUSION: Surgical removal of submacular CNV does not appear to improve visual acuity in patients > 50 years of age. However, it may be beneficial for younger patients where a substantial improvement of visual acuity is seen in a subset of these patients. Further studies are required to assess the long-term outcome. PMID- 11782224 TI - Thyroid associated ophthalmopathy: botulinum toxin A in the treatment of upper eyelid retraction--a pilot study. AB - PURPOSE: Eyelid retraction in patients with thyroid associated ophthalmopathy is a common cause of eye discomfort and a disfigured facial appearance. The aim of this pilot study was to evaluate the effects and safety of inducing a temporary partial ptosis of the eyelid through injection of botulinum toxin A into the levator palpebrae superioris muscle. METHODS: Nine patients were treated. They were followed up with ophthalmologic examinations and self-assessment questionnaires until the point at which they either required renewed treatment or had no residual effect of the first injection. Maximum follow-up time was twenty weeks. RESULTS: In all eyes but one there was a lowering of the eyelid position one week after treatment and all these patients reported an improvement of eye appearance and symptoms. There was variability in the degree of lowering of the eyelid with the same dose of injected botulinum toxin A. It was also difficult to predict the time interval needed for re-treatment. Ptosis impairing visual acuity was not a consequence of the treatment in any of the patients. One week after treatment two patients experienced increased diplopia but only one showed transient change in Lees screen measurement of eye motility. CONCLUSION: Botulinum toxin A injection may be used to lower the upper eyelid position in patients awaiting eyelid surgery. The treatment safely relieved symptoms and improved eye appearance. However, treatment was short term and difficult to predict. There is also an inherent risk of transient diplopia. PMID- 11782225 TI - Visual acuity, residual amblyopia and ocular pathology in a screened population of 12-13-year-old children in Sweden. AB - PURPOSE: To establish the distribution of visual acuity and the prevalence of residual amblyopia and other ocular disorders in a vision-screened population group of 12-13-year-old children. METHODS: In total 1046 children were examined in a field study in Sweden. The examination included visual acuity, stereopsis, cover testing, red reflex, refractive retinoscopy and examination of the posterior pole. In selected cases VEP was also performed. RESULTS: Visual acuity > or =1.0 in at least one eye was present in 98% of cases. Residual amblyopia (< or =0.5) was found in 1.1% of the population. Manifest strabismus was found in 2.7%. There were only a small number of ocular opacities and posterior pole abnormalities. Ocular albinism was found in 7 cases. In 15 children the cause of subnormal VA was unexplained. CONCLUSION: Results for visual acuity, residual amblyopia and other ocular disorders are very similar to previous Nordic, vision screened populations. PMID- 11782226 TI - Classification of the spectrum of Coats' disease as subtypes of idiopathic retinal telangiectasis with exudation. AB - PURPOSE: An increasing variety of eponymous terms have been used to describe atypical cases of Coats' disease. A group of typical cases of Coats' disease and other cases of differing severity were classified as one of four subtypes of idiopathic retinal telangiectasis with exudation and compared with regard to clinical outcome. METHODS: In a retrospective clinical review patients with typical and atypical Coats' disease were classified as severe, focal, juxtafoveal or associated (with another disease) forms of idiopathic retinal telangiectasis with exudation. RESULTS: 53 eyes in 50 patients were examined of which 62% (n=31) were male. 12 eyes were classified as severe (group 1), 22 focal (group 2), 12 juxtafoveal (group 3) and 7 associated (group 4). The mean age at diagnosis was lowest in group 1 eyes (6.8 years). The best visual acuity at presentation was 6/60 in group 1 whereas high proportions of eyes in the other groups had initial visual acuities of 6/24 or better. In group 1 only one eye was treated, the majority of eyes were blind or had been enucleated whereas 34 (79%) of eyes in the other groups were suitable for treatment and 29 eyes (67%) retained pre treatment visual acuity or better at last follow-up. CONCLUSIONS: Idiopathic retinal telangiectasis with exudation is a spectrum of disease, which is synonymous with Coats' disease. In this retrospective study eyes with severe idiopathic retinal telangiectasis with exudation corresponding to typical Coats' disease, have poorer vision at presentation, are less suitable for treatment and have worse outcomes than eyes with other subtypes. The spectrum of disease severity seen in idiopathic retinal telangiectasis with exudation may be due to second somatic mutations in genes with an existing germline mutation (the two hit theory) and a mosaic phenotype. PMID- 11782227 TI - Repeated UVR exposures cause keratocyte resistance to apoptosis and hyaluronan accumulation in the rabbit cornea. AB - PURPOSE: To evaluate hyaluronan (HA) production and level of apoptosis of corneal cells after repeated UVR exposures. METHODS: Fifteen albino rabbit corneas were exposed to 310 nm UVR at a dose that causes biomicroscopically significant keratitis (0.47 J/cm2). Nine rabbits received a single dose of UVR. Six rabbits were irradiated 3 times at 7-day intervals. Rabbits exposed to the single dose of UVR, were sacrificed 24 hours, 7 and 14 days after irradiation. Rabbits exposed to the repeated doses of UVR, were sacrificed 24 hours and 14 days after the last irradiation. The corneal tissue specimens were processed for histological analysis using specific staining for HA, and the TdT-dUTP terminal nick-end labeling (TUNEL) assay. RESULTS: Corneas exposed to a single UVR dose showed extensive positive TUNEL staining 24 hours after exposure. Almost all basal epithelial cells, keratocytes throughout the entire thickness of the stroma, and endothelial cells were TUNEL-positive. No HA was found 24 hours after exposure. Extracellular HA staining of high intensity was found at day 7 throughout the entire central stroma, except the anterior one-fourth. At day 14 only a faint HA staining was detected in the posterior stroma, close to Descemet's membrane. Corneas exposed to repeated UVR doses showed at 24 hours positive TUNEL staining only in epithelial cells and in very few stromal cells. The majority of stromal cells and endothelial cells were unaffected. At the same time HA staining of very high intensity was found both at 24 hours and day 14, and it was evenly distributed throughout the entire thickness of the stroma. CONCLUSION: Repeated UVR exposures lead to increased production and accumulation of HA in the corneal stroma. The repopulated keratocytes are much more resistant to apoptosis than the native ones. HA accumulation may be a sign of long-term changes in the cornea. PMID- 11782228 TI - Corneal grafting for keratoconus in mentally retarded patients. AB - PURPOSE: To compare the results of penetrating and non-penetrating corneal grafting procedures in mentally retarded keratoconus patients. METHODS: In the years 1974-2000 41 mentally retarded patients with keratoconus (33 with Down syndrome) were operated with corneal grafting. Mean age at operation was 36.7+/ 10.8 years. Three different surgical procedures were used (no randomization): penetrating keratoplasty (n=16), lamellar keratoplasty (n=5) and epikeratophakia (n=20). In a retrospective study, the non-penetrating procedures (lamellar keratoplasty and epikeratophakia) were compared to the penetrating keratoplasties with regard to graft survival and frequency of serious complications. Mean follow up time of all grafting procedures was 80+/-58 months. RESULTS: All cases of serious complications (irreversible rejection, wound leakage or perforation) occurred in the penetrating keratoplasty group (p=0.0005). Older age at operation (p=0.011) adversely influenced the frequency of serious complications. Overall five-year survival was 74.9%. Graft survival was not related to surgical procedure, but rather to age at operation (poorer survival in older age, p=0.012) and degree of retardation (poorer survival in patients with more severe retardation, p=0.051). CONCLUSIONS: Because of the safety and low frequency of complications, epikeratophakia is recommended as the grafting procedure of choice in the majority of mentally retarded with keratoconus. In selected cases (good cooperation, age < or =40 years, and a good peripheral corneal thickness) penetrating keratoplasty may be performed, which, if uncomplicated, often will give better functional/optical results. PMID- 11782229 TI - Biometric measurements of the eyes in teenagers and young adults with Down syndrome. AB - PURPOSE: To examine ocular biometric variables in subjects with Down syndrome. METHODS: In a population-based study we have compared ocular biometric variables in a group of 47 individuals with Down syndrome (20.0+/-3.9 years) with 51 control subjects (21.0+/-4.6 years). RESULTS: A thinner cornea (0.48+/-0.04 mm vs. 0.55+/-0.03 mm, p<0.001) and higher keratometry values (46.39+/-1.95 D vs. 43.41+/-1.40 D, p<0.001) were found in the Down syndrome group than in the control group. Oblique astigmatism was commonly found in the Down syndrome individuals, showing a strong right-left specificity (right eyes' axes in the 135 degrees -meridian, left eyes' axes in the 45 degrees -meridian). The lens was thinner (3.27+/-0.29 mm vs. 3.49+/-0.20 mm) and the calculated lens power was weaker (17.70+/-2.36 D vs. 19.48+/-1.24 D) in the Down syndrome group than in the control group (p<0.001 in both cases). CONCLUSIONS: Thinning of the corneal stroma may account for the steeper cornea and the high frequency of astigmatism in Down syndrome due to lower corneal rigidity. It may also be of etiological importance to the increased incidence of keratoconus in Down syndrome. PMID- 11782230 TI - Neoplasia versus hyperplasia of the retinal pigment epithelium. A comparison of two cases. AB - PURPOSE: To present the clinical and histopathological characteristics of two different tumor-like lesions of the retinal pigment epithelium (RPE). METHODS: Two cases of tumor-like lesions of the RPE were identified in the files of the Eye Pathology Institute. The clinical characteristics and the light- and electron microscopical morphology of the lesions were compared and the diagnoses were re evaluated applying modern immunostainings. RESULTS: Clinically, both adenoma and tumor-like hyperplasia of the RPE may present with prominent retinal feeder arterioles. The lesions are hypofluorescent in the filling phases and have multiple hyperfluorescent zones in the late phase in fluorescein angiography. They show high internal reflectivity by A-scan and appear as solid tumors by B scan ultrasonography. Histologically, the two presented lesions of the RPE are different. The first is an adenoma of the vacuolated subtype. The other lesion is a hyperplasia of the RPE disclosing a tubular morphology. The pathologically active cells in both cases were positive for the reaction with antibodies against: cytokeratin, NSE, vimentin, S-100, HMB-45, desmin and SMA. However, only the adenoma was sporadic melan-A positive. CONCLUSION: Adenomas and tumor-like hyperplastic lesions of the RPE are very rare lesions. They share many morphological and immunohistological characteristics. Of the presented cases only the RPE adenoma is sporadic melan-A positive. PMID- 11782231 TI - Stabilisation of refractive power after penetrating keratoplasty. PMID- 11782233 TI - Treatment strategies for post-traumatic stress disorder: need for brief and effective interventions. PMID- 11782234 TI - Post-traumatic stress disorder: a review of psychobiology and pharmacotherapy. AB - OBJECTIVE: To review the literature on the psychobiology and pharmacotherapy of PTSD. METHODS: Relevant studies were identified by literature searches (Pub-med, Web of Science) and through reference lists. The search was ended by May 2001. RESULTS: There is evidence of involvement of opioid, glutamatergic, GABAergic, noradrenergic, serotonergic and neuroendocrine pathways in the pathophysiology of PTSD. Medications shown to be effective in double-blind placebo-controlled trials includes selective serotonin reuptake inhibitors, reversible and irreversible MAO inhibitors, tricyclic antidepressants and the anticonvulsant lamotrigine. Still more agents appear promising in open-label trials. CONCLUSION: The complexity of the psychobiology is reflected by the difficulties in treating the disorder. According to the present knowledge, suggestions for drug treatment of PTSD are made. PMID- 11782235 TI - Effectiveness of psychological debriefing. AB - OBJECTIVE: To identify literature concerning the effectiveness of psychological debriefing (PD) and analyse results according to different criteria of success and different uses of the intervention format. METHOD: Literature search was made in databases PubMed, PsycInfo and Psychlit. Twenty-five studies were selected for a thorough description. Forty-two studies provided additional information. RESULTS: Results indicate that, in general, debriefing does not prevent psychiatric disorders or mitigate the effects of traumatic stress, even though people generally find the intervention helpful in the process of recovering from traumatic stress. The intervention holds potential as a screening procedure, and there may be economic arguments for continued use. When used with adherence to traditional descriptions of treatment group, events, group format, leadership and time spent, a preventive effect emerges. No tendency according to timing was found. CONCLUSION: Current uses of PD are problematic. The concept needs to be redefined, and the scope of application must be revised. The objectives for use need to be clarified. PMID- 11782236 TI - Psychological consequences of the 1998 landslide in Sarno, Italy: a community study. AB - OBJECTIVE: This community study assessed the prevalence of post-traumatic stress disorder (PTSD) and the psychosocial consequences of the landslide which occurred in Sarno, Southern Italy, in May 1998. METHOD: A random sample (n=272) of the population living in the highest risk area of Sarno, and a control group recruited in a small town situated near the disaster area, but not affected by the event, were assessed 1 year after the disaster by standardized instruments. RESULTS: Of the subjects recruited in Sarno, 27.6% met DSM-IV criteria for PTSD; 59% subjects recruited in Sarno and 35% of the control group were identified as "probable cases" by the GHQ-30 (P<0.0001). Subjects recruited in Sarno had significantly higher scores on the four GHQ-30 subscales identified by factor analysis. CONCLUSION: This study emphasizes the negative impact of a natural catastrophic event on mental health, and the need for preventive interventions. PMID- 11782237 TI - Increasing rates of suicide in Western Australian psychiatric patients: a record linkage study. AB - OBJECTIVE: To investigate the risk of suicide following contact with mental health services and whether it has changed over time. METHOD: Record linkage was used to obtain the records of previous hospital admissions and mental health service contacts for deaths due to suicide in the period 1980-98. Standardized incidence rates were calculated for the general population and for users of mental health services. Proportional hazards regression was used to assess risk factors within the cohort of people with mental health service contact. RESULTS: Suicide risk was significantly increased in users of mental health services (rate ratio 6.66 in males and 7.52 in females). Suicide risk was highest in the first 7 days after discharge from in-patient care, and decreased exponentially with time since discharge. Suicide risk in users of mental health services has increased over the study period. CONCLUSION: These results highlight the importance of adequate follow-up of patients discharged from in-patient services, and the need for adequate resources for community-based services. PMID- 11782238 TI - The validity of proxy-based data in suicide research: a study of patients 50 years of age and older who attempted suicide. II. Life events, social support and suicidal behavior. AB - OBJECTIVE: To investigate the validity of proxy respondent reports of stressful life events, social support and suicidal behavior among individuals who attempted suicide. METHOD: Subjects were 80 psychiatric in-patients admitted following a suicide attempt. Data based on structured interviews with proxy respondents were compared with data based on interviews with subjects (gold standard). RESULTS: Specificity was higher than sensitivity across life event categories, and agreement was substantial for public and observable events (e.g. parent's death) but lower for more ambiguous events. Proxies were good judges of subject reports of frequency of social interaction but not perceived emotional support. Proxies were good judges of past history of suicide attempts and level of suicidal intent. CONCLUSION: Results support proxy-based data on suicidal behavior and certain aspects of social support and stressful life events in research of suicidal behavior in this age group, with potential implications for interpreting postmortem research of completed suicide. PMID- 11782240 TI - Mental abilities of male relatives of psychotic patients. AB - OBJECTIVE: Exploration of academic and creative potentials of first-degree relatives of hospital-treated psychotic patients in Iceland. METHOD: Relatives identified in a previously published family study of psychosis are evaluated, using records available at the National Archives and National Library in Reykjavik. Performance of groups of relatives is compared to that of the general population. RESULTS: Healthy relatives of patients are found to excel over others in authorship of books of fiction or poetry, in general school performance at age 20 years and in mathematics. These findings apply to both schizophrenia and affective illness. CONCLUSION: Relatives of psychotic patients often exhibit good mental abilities. PMID- 11782239 TI - Psychopharmacological treatment and psychiatric morbidity in 390 cases of suicide with special focus on affective disorders. AB - OBJECTIVE: The aim of this study was, on the basis of data from health-care registers, to describe the adequacy of psychopharmacological treatment in suicides. METHOD: Data on consecutive suicides in a Danish County (Funen) in the period of 1 April 1991-31 December 1995 were identified in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense University Pharmacoepidemiological Database. RESULTS: Twenty-five per cent of the suicides previously hospitalized due to affective disorders and 3% of the suicides without psychiatric hospitalizations at all, received an apparently adequate treatment with antidepressants the month before suicide. CONCLUSION: The most striking finding was the insufficiency of treatment with antidepressants in the group of suicides without psychiatric hospitalization, in particular in light of the fact that depression is assumed to be present in at least 50% of all suicides. PMID- 11782241 TI - Donepezil in schizophrenia--is it helpful? An experimental design case study. AB - OBJECTIVE: To assess the clinical and cognitive effects of adding donepezil, a reversible acetylcholinesterase inhibitor, to the risperidone treatment of a high functioning stable out-patient with schizophrenia. METHOD: Case study using an experimental ABAB design. Assessments were completed objectively by standardized neuropsychological tests and clinical rating scales and subjectively with visual analogue scales. RESULTS: Strong improvements attributable to donepezil were found for verbal fluency and the patient's subjective response. No adverse changes were noted in psychiatric symptoms or side effects. CONCLUSION: Cholinergic enhancement as an adjunctive treatment in schizophrenia should be explored in larger controlled trials. PMID- 11782242 TI - Thromboembolism after physical restraint. PMID- 11782243 TI - Non-human primates: essential partners in biomedical research. PMID- 11782244 TI - Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications. AB - Opsonization of particulate pathogens by antibodies and complement can lead to their binding to the complement receptor (CR1), specific for C3b, on primate erythrocytes (E). This process of immune adherence may play a role in immunologic defense by immobilizing bacteria and viruses, thus preventing them from leaving the bloodstream to invade susceptible tissue and organs. Immune adherence of C3b opsonized and immune complexed pathogens to E may also facilitate their transfer to, and destruction by, fixed tissue macrophages. We have used mAbs specific for CR1 crosslinked with pathogen specific mAbs to generate heteropolymers (HP) which can bind a wide range of substrates to primate erythrocytes. Both prototype and bonafide pathogens bound to primate E via HP are handled in the circulation of non-human primates in a manner which appears to be virtually identical to the mechanism by which C3b-opsonized substrates bound to E CR1 are cleared. In this process of focused phagocytosis, Fc receptors on the phagocytic cell engage the E bound complex, CR1 is removed by proteolysis, and the entire immune complex and CR1 are internalized while sparing the E. It may be possible to use HP to target pathogens in the bloodstream in a wide range of therapeutic applications. PMID- 11782246 TI - Species-specific evolution of MHC class I genes in the higher primates. AB - Humans express three highly polymorphic 'classical' (HLA-A,B and C) and three conserved 'non-classical' (HLA-E, F and G) MHC class I genes. Their comparison with the MHC class I genes of apes and monkeys reveals the differential extent to which MHC class I genes have been preserved during primate evolution. African apes have orthologues of all six human genes, and although allelic lineages of the A and C loci are shared, these species share none of the human alleles. In Asian apes, several MHC class I genes show significant differences from the human genes, a trend which continues with the Old World monkeys, and even more so in the New World monkeys, where E and F are the only human gene orthologues. The C locus is confined to humans and apes. Multiple A-related and B-related loci have been identified in apes and Old World monkeys showing that duplication of these loci has been a common event during primate evolution. Certain of the daughter loci exhibit low polymorphism, suggesting they have adopted a non-classical function. The differing rates at which MHC class I genes have evolved during primate evolution likely reflects their differing functions in the immune response. PMID- 11782245 TI - The KIR and CD94/NKG2 families of molecules in the rhesus monkey. AB - Natural killer (NK) cells and a subset of T cells express families of receptors that are capable of detecting major histocompatibility complex (MHC) class I expression on the surface of cells. Molecules of the killer cell immunoglobulin like receptor (KIR) family bind directly to MHC class I, while those of the CD94/NKG2 family recognize MHC class I signal sequences bound to HLA-E. Both the KIR and CD94/NKG2 families are composed of activating and inhibitory molecules that serve to regulate the function of NK cells as a result of their MHC class I recognition. Here we review the recently described KIR and CD94/NKG2 family members in the rhesus monkey. PMID- 11782247 TI - The evolution of the MHC-G gene does not support a functional role for the complete protein. AB - The study of the MHC-G gene evolution during nearly 40 million years does not support a role for the full molecule. The MHC-G-like proteins of New World monkeys are probably classical presenting molecules. Old World Cercopithecinae monkeys do not have a full MHC-G molecule and human individuals homozygous for the HLA-G null allele are healthy and do not show birth pathologies. PMID- 11782248 TI - Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies. AB - The rhesus macaque is an important preclinical model in transplantation research and in investigations of chronic and infectious diseases that need a well characterised major histocompatibility complex (MHC-Mamu). In a large population of pedigreed rhesus macaques, 70 Mamu-DRB, 18 -DQA1, 24 -DQB1, and 14 -DPB1 alleles were detected. In humans, five HLA-DRB region configurations are present, displaying diversity with regard to number and combinations of loci. The HLA-DRB1 gene of each of these configurations is highly polymorphic. For rhesus monkeys, at least 31 Mamu-DRB region configurations have been determined. In contrast to humans, most Mamu-DRB region configurations display no or only limited allelic polymorphism. Segregation analyses revealed 28 Mamu-DQA1/DQB1 pairs, each pair linked to a limited number of Mamu-DRB region configurations and vice versa. In comparison with humans, the degree of freedom of recombination between Mamu-DQA1 and -DQB1 is extremely low and equivalents of HLA-DQA2/DQB2 are absent. The Mamu DPA1 gene is invariant and -DPB1 manifests only moderate allelic variation, whereas the HLA-DPA1 gene is oligomorphic and HLA-DPB1 highly polymorphic. Thus, both species used different evolutionary strategies to create polymorphism and diversity at the MHC class II loci in order to cope with pathogens. PMID- 11782249 TI - Chimpanzee models for human disease and immunobiology. AB - Chimpanzees have greater than 98% genomic sequence homology with humans but have significantly more favorable responses to human immunodeficiency virus (HIV)-1 and hepatitis B virus (HBV) and an apparently low incidence of epithelial malignancy. Although there are few shared major histocompatibility complex (MHC) alleles between human and chimp, there is considerable overlap in binding repertoires for epitopes of HIV-1 and HBV. This indicates that differences in viral handling may be due to involvement of cells other than T lymphocytes. Similar mechanisms may be involved in host response to dysplastic or malignant cells. In seeking to understand these differences, most attention has been focused on comparing and contrasting well-characterized steps in immune response. As an additional possibility, alterations in cell-cell interactions dependent upon sialic acid binding proteins known to be involved in immune responses should also be considered. The lack of a particular sialic acid structure (N-glycolyl neuraminic acid, or Neu5Gc) in humans, due to a gene mutation in an essential synthetic enzyme, has potentially altered the kinetics of cellular responses dependent upon these lectins. The absence of Neu6Gc represents the only known major biochemical difference between humans and chimpanzees. PMID- 11782250 TI - Determining the immune mechanisms of protection from AIDS: correlates of immunity and the development of syngeneic macaques. AB - The AIDS pandemic is a global emergency and a preventive vaccine is urgently needed. CD4 and CD8 T-cell responses appear important in controlling human immunodeficiency virus (HIV)-1 in humans and simian immunodeficiency virus (SIV) in macaques. The utility of vaccines that induce high levels of SIV- or HIV specific T cells has recently become clearer. Since T cells recognize virus infected cells rather than free virus, T-cell-based vaccines only have the capacity to control infections (non-sterilizing immunity) and to prevent continuing or persisting infection. An HIV/SIV infection of macaques that is partially controlled by vaccine-induced T-cell responses permits a critical window of opportunity for the efficient generation and recruitment of additional T- and B-cell immune responses to the incoming viral inoculum. Although CD8 depletion experiments in macaques have defined the utility of CD8 T responses in control of SIV infections in macaques, direct evidence on the utility of either CD4 or CD8 T-cell responses in protective immunity to SIV following vaccination is lacking. The availability of genetically identical macaques would allow cell transfer studies and help define with more certainty the role of cellular immune responses in protection from AIDS. The review also focuses on the development of syngeneic macaques by twinning and cloning technologies. PMID- 11782251 TI - Virus replication and evolution drive the kinetics and specificity of SIV specific cytotoxic T lymphocytes. AB - SIV (simian immunodeficiency virus) infection of cynomolgus macaques provides an excellent model for investigating the basis of protective immunity against HIV (human immunodeficiency virus). We explored the protective role of cytotoxic T lymphocytes (CTL) against the pathogenic molecular clone SIVmac-J5. Vaccine induced CTL precursors (CTLp) against Env, Gag or Nef did not protect macaques against intravenous challenge. However, detection of Rev-specific CTLp in infected macaques was associated with effective virus containment. Furthermore, CTL against an immunodominant Gag/p26 epitope (amino acids 242-250) resulted in the emergence of a mutant virus that uniformly replaced wild-type virus in the spleen and partially escaped recognition. During primary infection, CTLp detection in blood coincided with decreasing viremia. After 12 months, two outcomes emerged. In one group of macaques, persistent viremia was associated with high viral load in lymphoid organs and declining CD4+ T-cell counts. CTLp were maintained in asymptomatic macaques, but declined in the symptomatic phase of infection. In a second group, loss of detectable viremia was associated with low-level virus reservoirs in lymphoid organs, asymptomatic status and maintained CD4+ T-cell counts. CTLp peaked in the first 4 months of infection and subsequently declined in this group. These studies provide insights into the complex interplay between virus replication and host immunity. PMID- 11782252 TI - Understanding cytotoxic T-lymphocyte escape during simian immunodeficiency virus infection. AB - Infection of rhesus macaques with simian immunodeficiency virus (SIV) is an excellent model system for studying viral adaptation to immune responses. In this review, we discuss how the SIV-infected macaque has provided unequivocal evidence for cytotoxic T-lymphocyte (CTL) selection of viral escape variants. This improved understanding of CTL escape may influence human immunodeficiency virus (HIV) vaccine design as well as our understanding of HIV pathogenesis. PMID- 11782253 TI - Baboons as an animal model for human immunodeficiency virus pathogenesis and vaccine development. AB - Baboons (Papio cynocephalus) provide a valuable animal model for the study of human immunodeficiency virus (HIV) pathogenesis because HIV-2 infection of baboons causes a chronic viral disease that progresses over several years before clinical signs of acquired immunodeficiency syndrome (AIDS) appear. Since HIV-2 infected baboons develop a chronic viral infection, insights into the immuno biology of viral latency, clinical stages of disease, virus infection of lymphatic tissue and HIV transmission can be gained using this animal model. The development of an AIDS-like disease in baboons is viral isolate and baboon subspecies dependent. Thus, viral virulence factors and host resistance can be studied as well as the mechanisms of innate and acquired immunity. The control of virus infection is dependent upon cytotoxic and non-cytotoxic antiviral activity of CD8+ T cells. In this regard, some of the HIV-2-infected baboons develop potent antiviral cellular immune responses that have a similar magnitude to that found in HIV-1-infected long-term survivors (or non-progressors). In our laboratory, baboons have been used to study DNA vaccine strategies using new cationic liposome formulations and granulocyte macrophage-colony stimulating factor and B7-2 as genetic adjuvants. The results demonstrate the value of using baboons as an animal model of AIDS pathogenesis and vaccine development. PMID- 11782254 TI - Immune evasion strategies of the primate lentiviruses. AB - Individuals infected with human immunodeficiency virus (HIV) and macaques infected with simian immunodeficiency virus (SIV) make vigorous virus-specific antibody and cellular immune responses. Despite these responses, virus replication continues at all stages of infection and ultimately leads to immunological collapse, onset of opportunistic infections and death of infected hosts. Thus, the strategies by which HIV and SIV evade antiviral immune surveillance are fundamental to understanding lentiviral pathogenesis and crucial for our ability to develop effective strategies. It has become increasingly clear that the primate lentiviruses have evolved multiple and complementary mechanisms to circumvent host immune responses. Here we review these mechanisms of immune evasion considering contributions from both human and non-human primate systems. PMID- 11782255 TI - Experimental allergic encephalomyelitis in the New World monkey Callithrix jacchus. AB - Models that adequately reflect the complexity of human multiple sclerosis (MS) are needed, especially for preclinical testing of immunomodulatory drugs. Our group has created a unique experimental system in a New World outbred primate, the common marmoset Callithrix jacchus (C. jacchus). Following immunization with myelin, these monkeys develop a chronic, relapsing-remitting form of experimental allergic encephalomyelitis (EAE), which pathologically recapitulates the hallmark features of lesions of human MS. The MS-like lesion in C. jacchus results from a complex immune response against myelin antigens and requires both T cells and pathogenic antibodies. Studies of C. jacchus EAE have permitted the identification of a major target for pathogenic autoantibodies in MS, the myelin/oligodendrocyte glycoprotein. Other advantages of the model include a natural bone-marrow chimerism, which permits T-cell adoptive transfers between siblings, and the possibility of using different antigens to produce either inflammatory or demyelinating phenotypes of EAE. Despite their small size, sequential in vivo imaging and immunological studies are possible in these monkeys, and have been used to monitor efficacy in preclinical trials. Due to close phylogeny and high homology of immune and nervous system genes with humans, this model should fast-track the development of novel therapeutics for MS. PMID- 11782256 TI - Non-human primate models of multiple sclerosis. AB - The phylogenetic proximity between non-human primate species and humans is reflected by a high degree of immunological similarity. Non-human primates therefore provide important experimental models for disorders in the human population that are caused by the immune system, such as autoimmune diseases. In this paper we describe non-human primate models of multiple sclerosis, a chronic inflammatory and demyelinating disease of the human central nervous system. While reviewing data from the literature and our own research we will discuss the unique role of such models in the research of basic disease mechanisms and the development of new therapies. PMID- 11782257 TI - The rhesus model of Lyme neuroborreliosis. AB - Similarity of pathology and disease progression make the non-human primate (NHP) model of Lyme neuroborreliosis appropriate and valuable. In the NHP model of Lyme neuroborreliosis, spirochetal density in the nervous system and other tissues has been measured by polymerase chain reaction and correlated to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid and to inflammation in tissues. Despite the demonstrable presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, only minor inflammation of the central nervous system occurs, though inflammation can be demonstrated in other tissues. Infected animals also develop anti-Borrelia burgdorferi antibody in the serum, although increased amplitude of antibody is not predictive of higher levels of infection. The NHP model continues to provide important insight into the disease process in humans. PMID- 11782258 TI - Tolerance and near-tolerance strategies in monkeys and their application to human renal transplantation. AB - Studies in non-human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non-human primates are T-cell depletion by anti-CD3 immunotoxin and co-stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non-human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non-human primates. However, there has not been a one-to-one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non-human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non human primates. PMID- 11782259 TI - Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates. AB - Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co stimulatory molecules, especially the CD40-CD154 pathway, have great potential for clinical adaptation. While the combination of anti-CD154 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40-CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical trials. Work in the non human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. It also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunomodulatory approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic. PMID- 11782260 TI - STEALTH matters: a novel paradigm of durable primate allograft tolerance. AB - We review a novel strategy for tolerance induction developed in rhesus macaques and termed STEALTH. We summarize the evolution of the STEALTH model, the results of successful trials in inducing long-term, stable transplant tolerance in rhesus kidney and diabetic islet recipients and discuss information related to the mechanism by which durable tolerance is induced. STEALTH tolerance is induced by a 3-day treatment course of CD3epsilon immunotoxin (IT) combined with a 14-day treatment with deoxyspergualin (DSG). IT causes profound depletion of sessile lymph node T cells as well as the more accessible circulating T cells. DSG, an inhibitor of HSC 70-mediated NF-kappaB nuclear translocation, arrests maturation of myeloid dendritic cells, blocks production of proinflammatory cytokines induced by IT administration, and promotes systemic production of Th2 type cytokines that persist indefinitely. Such Th2 cytokine deviation has not been reported in NHP transplant recipients. These studies provide proof of principle in a preclinical model that prevention of both acute and chronic allograft rejection, for at least 2.2-4.9 years of follow-up, can be achieved in NHP in the absence of chronic immunosuppressive drugs or other interventions. This strategy for inducing NHP tolerance is discussed in relation to current tolerance paradigms. PMID- 11782262 TI - "On-line or non-line". PMID- 11782263 TI - Asymptomatic hypoechoic regions on patellar tendon ultrasound: A 4-year clinical and ultrasound followup of 46 tendons. AB - Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47+/-11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management. PMID- 11782264 TI - Non-operative treatment regime including eccentric training for lateral humeral epicondylalgia. AB - In a pilot study 38 patients with lateral humeral epicondylalgia were randomly allocated to two treatment groups. Group S (stretching) was treated with a contract-relax-stretching program while group E (eccentric exercise) underwent an eccentric exercise program. Both groups also received forearm bands and wrist support nightly. The programs were carried out daily at home during 12 weeks. Evaluation before and 3, 6 and 12 months after treatment, included subjective assessment of symptoms using visual analogue scales and grip strength measurements. Thirty-five patients were available for follow-up. Five patients, three in group S and two in group E, did not complete the programs due to increased pain while 30 (86%) reported complete recovery or improvement. Reduced pain and increased grip strength were seen in both treatment groups but 12 out of 17 patients (71%) in group E rated themselves as completely recovered as compared to 7 out of 18 (39%) in group S (P=0.09), and in group E the increase in grip strength after 6 months was statistically significantly larger than in group S. In a second study the eccentric training regime was used in a consecutive series of 129 patients with lateral epicondylalgia. The patients were divided into two groups with one group consisting of patients with less than one year duration of symptoms and the other comprised patients with a duration of symptoms for more than one year. The results of treatment were evaluated in the same way as in the pilot study, and also after 3.4 years using the scoring system by Verhaar et al. At the end of the treatment period statistically significant improvements were seen in all VAS recordings and in grip strength. After 3.4 years 38% had excellent, 28% good, 25% fair and 9% poor results according to the score. In the self-rated outcome 54% regarded themselves as completely recovered, 43% improved, 2% unchanged and 2% worse. No significant differences were seen between patients with a duration of symptoms for more than one year compared to patients with symptoms for less than one year. The eccentric training regime can considerably reduce symptoms in a majority of patients with lateral humeral epicondylalgia, regardless of duration, and is possibly superior to conventional stretching. PMID- 11782265 TI - The effects of three different training modalities on the cross-sectional area of the paravertebral muscles. AB - The purpose of this study was to determine the effect of different training schedules on the cross-sectional area (CSA) of the paravertebral muscles (PA) in chronic low back pain (CLBP) patients. To achieve this goal 59 patients were randomly assigned to three different 10-week rehabilitation programs: stabilization training (group 1, n=19), stabilization training combined with dynamic resistance training (group 2, n=20) and stabilization training combined with dynamic-static resistance training (group 3, n=20). The CSA of the PA was derived from standard computerized tomography (CT) images at three different levels. The CSA of the PA was found to increase statistically in group 2 (upper end-plate of L4) and group 3 (upper end-plate of L3 and lower end-plate of L4). In contrast, no statistical differences over time were found in group 1. Since stabilization exercises have no effect on the CSA of the PA, intensive lumbar resistance training seems to be necessary to restore the size of the PA in CLBP patients with atrophied back muscles. No systematic difference in hypertrophy between dynamic and dynamic-static strengthening training modes was found. PMID- 11782266 TI - Functional outcome of anterior cruciate ligament reconstruction in recreational and competitive athletes. AB - The aim of this study was to compare the outcome after anterior cruciate ligament reconstruction in recreational and competitive athletes, with a minimum follow-up of two years. Forty-nine patients (24 males and 25 females) who, at the time of the index injury, were classified as recreational athletes (Tegner level 2-5) were compared with 226 patients (61 females and 165 males) who, at the time of the index injury, were classified as competitive athletes (Tegner level 9-10). At the follow-up, no significant differences were found between the study groups in terms of the Lysholm score, IKDC evaluation system, one-leg-hop test, KT-1000 laxity measurements, anterior knee pain and the patients' subjective evaluation of the results. However, the competitive athletes displayed a significantly higher reduction in Tegner activity level than the recreational athletes. The functional and objective results after anterior cruciate ligament reconstruction were comparable for the recreational and competitive athletes. We, therefore, conclude that anterior cruciate ligament reconstruction could be recommended for recreational athletes as well as competitive athletes. PMID- 11782267 TI - The effect of short-term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels. AB - The effect of strength training and endogenously elevated hormone levels (plasma testosterone, growth hormone (GH) and cortisol) was studied in 16 young untrained males, divided into an arm only training group, A, and a leg plus arm training group, LA, in order to increase circulating levels of anabolic hormones. Both groups performed the same one-sided arm training for 9 weeks, twice a week. Group A trained only one arm (AT), the contralateral arm serving as control (AC), whereas group LA additionally trained their legs following the training of the one arm (LAT), with the contralateral arm serving as control (LAC). In spite of the attempt to match the two groups, the initial isometric arm strength was 20 25% lower for group LA compared to group A (significant for the arm to be trained). Isometric strength increased significantly in LAT and LAC by 37% and 10%, respectively, while the 9% and 2% increases in AT and AC, respectively, remained insignificant. Isokinetic strength increased at one out of three velocities tested for the trained arm relative to the untrained arm in both group A and group LA (P<0.05). Functional strength increased significantly by 20% in LAT, 18% in LAC, 19% in AT, and 17% in AC. Hormonal responses were monitored during the first and last training sessions. Resting hormone levels remained unchanged for both groups. However, during the first training session plasma testosterone as well as plasma cortisol increased significantly in group LA but not in group A. Plasma GH rose in all exercise tests, except during the last test in group LA, but was significantly higher in group LA than in group A in the first training session. In conclusion, a larger relative increase in isometric strength was found in the group having the highest hormonal response. However, due to the initial difference in isometric strength caution must be taken with the interpretation of this finding, which may only indicate a possible link between anabolic hormones and muscle strength with training. PMID- 11782268 TI - Specific pulmonary responses during the cycle-run succession in triathletes. AB - The aim of the present study was to investigate the relationship between alterations in pulmonary function (i.e., diffusing capacity for carbon monoxide and pulmonary volumes) and the ventilatory response elicited during the cycle-run succession in triathletes. Ten well-trained triathletes performed three exercises: 1) 30 min cycling plus 20 min of running, termed the cycle-run succession; 2) 30 min cycling; and 3) 20 min running. Before and 10 min after each trial, the triathletes underwent pulmonary function testing, including spirometry and diffusing capacity for carbon monoxide. During all trials, ventilatory data were collected every minute using an automated breath-by-breath system. The ventilatory response was significantly higher in the run subsequent to cycling as compared with the run performed independently (P<0.001). There was no change in pulmonary volumes before and after exercises; however, the diffusing capacity for carbon monoxide and the transfer coefficient were similarly decreased (P<0.05) after cycling and the cycle-run succession, but not decreased after running. The increase in minute ventilation in the run segment of the cycle run succession versus in running alone was significantly correlated with the decrease in diffusing capacity for carbon monoxide measured after versus before the cycle-run succession (P<0.01). This same increase in ventilation was also correlated with the decrease in diffusing capacity measured after the cycle-run succession versus after cycling alone (P<0.03). These results suggest the possibility that the DLCO decrease contributes in part to the ventilatory increase noted in the run after cycling during the cycle-run succession of the triathlon. PMID- 11782269 TI - Effects of 12-week shooting training and mode of feedback on shooting scores among novice shooters. AB - The mode of feedback has been shown to have an effect on motor skill learning. This study investigated effects of an intensive 12-week shooting training period, and of the mode of feedback on scores in standing and running target shooting among 30 novices with limited shooting experience. They were divided into one control (no training) and three training groups. One out of the three training groups received only KR (knowledge of results) while the two other groups received KR+KP (knowledge of performance). One of the KR+KP groups received additional visual feedback (FB-II group), which included videos, graphic and written materials about kinematic and kinetic characteristics of their respective shooting techniques compared to performance of international level shooters. Each training group improved their scores in the running target shooting. There were no significant differences between the three training groups in improvements of sum scores (performance outcome). The current study showed that among novice shooters both KR alone and KR+KP improved running target shooting outcome, and that KR and KP together did not lead to a significantly better shooting performance than KR alone. PMID- 11782270 TI - Sports medicine update. PMID- 11782272 TI - HLA class II polymorphism in Aka Pygmies and Bantu Congolese and a reassessment of HLA-DRB1 African diversity. AB - HLA-DRB1, -DQB1 and -DPB1 polymorphisms were investigated in two African populations, the Basse Lobaye Aka Pygmies of the Central African Republic, and a Bantu-speaking group from the Democratic Republic of Congo Kinshasa. Allelic and haplotypic frequency distributions reveal marked differences between the two populations in spite of their geographical proximity: the Aka exhibit high frequencies for several alleles, especially at the DPB1 locus (0.695 for DPB1*0402), probably due to rapid genetic drift, while the Bantu distributions are more even. Genetic distances computed from DRB1 allelic frequencies among 21 populations from North and sub-Saharan Africa were applied to a multidimensional scaling analysis. African populations genetic structure is significantly shaped by linguistic differentiation, as confirmed by an analysis of molecular variance. However, selective neutrality tests indicate that many African populations exhibit an excess of heterozygotes for DRB1, which is likely to explain the genetic similarity observed between some North African and Bantu populations. Overall, this study shows that natural selection must be taken into account when interpreting the patterns of HLA diversity, but that this effect is probably minor in relation to the stochastic events of human population differentiations. PMID- 11782273 TI - The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations. AB - The Caucasus and the Iberian peninsula have been connected from a linguistic (Basque and Kvartelian languages), toponimic and historic perspectives. They also represent places (e.g. Dmanisi in Georgia and Atapuerca in Northern Spain) where the oldest hominoid remains in Europe are being discovered and studied. These circumstances prompted us to study the genetic background of the Svans (living on the southern slopes of the Greater Caucasus in the Republic of Georgia) in comparison with Basques from the semi-isolated Arratia valley as well with other Northern Spanish and Western European populations. DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*1301-DQA1*0103-DQB1*0603 haplotypes were found in Svans at the highest frequency. The second most frequent three-locus haplotypes in this population were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1301-DQA1*0103-DQB1*0602. Furthermore, the following 5-locus extended haplotypes were not found in other populations: A3-B8-DRB1*11-DQA1*0501-DQB1*0301, A2-B8-DRB1*13-DQA1*0103 DQB1*0603, A2-B40-DRB1*14-DQA1*0104-DQB1*0501, A2-B51-DRB1*08-DQA1*0401 DQB1*0402, A3-B7-DRB1*03-DQA1*0501-DQB1*0201 and A24-B39-DRB1*08-DQA1*0401 DQB1*0402. Other haplotypes present in Svans were also frequently observed in Northern Spain and in other Western European countries. However, haplotypes reported as characteristic for Basques were not found in the Svans. A dendrogram using HLA class II alleles places the closest genetic distance observed between Svans and Czechs, whereas Slovenes and other Mediterranean populations (Jews, Hungarians, Frenchmen, Sardinians and Greeks) have the greatest genetic distance. When both HLA class I and class II alleles from 17 populations were compared, the smallest genetic distances were with Rumanians, Czechs and Armenians. Northern Spanish populations were placed closer to each other and clearly separated from Svans. In conclusion, the Svan population shows considerable polymorphism. These observations suggest a mixture of alleles in Svans from geographically distinct areas, and probably do not support a common ancestor for these Caucasian inhabitants and people from Northern Spain. PMID- 11782274 TI - CD27 expression in the human splenic marginal zone: the infant marginal zone is populated by naive B cells. AB - The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants and children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM-1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone. Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response. PMID- 11782275 TI - MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. AB - MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by gammadelta T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA-B and TNFalpha. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA-B gene, in patients of Caucasoid origin with Crohn's disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis. We could also not discover any associations of specific two point or three-point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample. PMID- 11782276 TI - HLA-DRB fluorotyping by dark quenching and automated analysis. AB - In fluorescence-based sequence-specific primed polymerase chain reaction (PCR), referred to as fluorotyping for HLA typing, a major problem is the overlap of the emission spectra of the single dyes. In order to increase the robustness of the previously described HLA-DRB1,3,4,5 low-resolution fluorotyping method, we have constructed two probes quenched by the non-fluorescent acceptor dye DABCYL. The HLA-DRB-specific probe was labeled with FAM, and the internal control probe with TAMRA, respectively, as reporter fluorescent dyes. TAMRA was replaced by DABCYL as a quencher, which led to increased robustness and better discrimination between negative and positive amplification results. ROX was used as a reference to normalize the fluorescence of the reporter dyes. Moreover, as FAM and TAMRA differ strongly by their emission maxima, HLA-DRB-specific and internal control amplification could be clearly distinguished. To further automate data analysis, the software of the TaqMan system 7700 was supplemented by an EXCEL-based calculation table, which directly took over the data. Using modified fluorotyping chemistry and automated data analysis, a total of 201 DNA samples was typed correctly. In summary, HLA-DRB fluorotyping by dark quenching and automated analysis proved to be a robust and reliable tool for research and routine purposes. PMID- 11782277 TI - Identification of novel single nucleotide substitutions in the NKp30 gene expressed in human natural killer cells. AB - Cytotoxicity of natural killer (NK) cells is regulated by a balance of signals from two kinds of NK receptors, activating receptors and inhibitory receptors. Natural cytotoxicity receptors (NCR) family, which consists of NKp30, NKp44 and NKp46, is a major human activating NK receptor. NKp30 has been mapped to the HLA class III region near tumor necrosis factor (TNF) family loci. We have analyzed the NKp30 gene of healthy Japanese and found two synonymous substitutions in the coding region, c.111G>A and c.156C>T, and also identified two single-nucleotide polymorphisms (SNPs) in the promotor region, -201G>A and -163G>C. Furthermore, it was confirmed that these polymorphisms of the NKp30 gene show strong linkage disequilibria with each other and with HLA-DRB1 or TNFA polymorphisms. Since susceptibilities to certain diseases were mapped near this region, the NKp30 polymorphisms could be useful genetic markers. PMID- 11782278 TI - New insights regarding HLA-B27 diversity in the Asian population. AB - A polymerase chain reaction-sequence-specific primer (PCR-SSP) method which distinguishes all B27 alleles described at present (B*2701-23) has been developed. The distribution of B27 alleles was characterised in six different Asian populations. HLA-B*2705, 02, 04, 07, 22 (formerly B*2706) subtypes found in Asian populations differ in their ethnic distribution, which may be the result of different genetic and geographic origins. Furthermore, two novel B27 alleles were found in this study. B*2714 was identified in two Siberians, one of whom was a patient with ankylosing spondylitis. B*2715 was found in two patients with ankylosing spondylitis in Thais. These associations have not previously been reported in either ethnic group. PMID- 11782279 TI - Identification of a novel HLA-B*2722 allele from a Filipino cell. AB - We present the novel HLA-allele B*2722 amplified and sequenced from a Filipino individual. This DNA was included several times in the International Cell Exchange, UCLA, and typed at the time as B*27 or B*2706 by the majority of the participating laboratories. The second HLA-B allele of this person is B*3802. B*2704/06 or B*2704/06/10 were suggested by approximately one-third of the laboratories. As we were investigating the intron 3 sequences of B*27 alleles, we also sequenced exon 4 of this Filipino DNA and found a single nucleotide exchange in exon 4 (pos. 704) which was not in concordance with the previous B*2706 typing. Our sequencing results showed that the coding sequence of B*2722 is identical to B*2706 in exon 1, 2 and 3. In exon 4 the B*2722 sequence is identical to B*2704. HLA-B*2704 differs from B*2706 in one base at position 704, a G in B*2704 and a C in B*2706, respectively. PMID- 11782280 TI - Identification of a novel HLA-DQB1*06 allele, DQB1*0618. AB - We report here the identification of a novel DQB1*06 allele, DQB1*0618, found in a bone marrow donor. The new allele was detected during routine DNA-based HLA typing by an ambiguous pattern of probe hybridization, obtained by polymerase chain reaction using sequence-specific oligonucleotides (PCR-SSO). Molecular cloning and sequencing confirmed that the new allele is identical to DQB1*0609 at exon 2 except for 3 nucleotide substitutions at positions 353, 356 and 367, also found in other alleles. These nucleotide changes may explain its anomalous reactivity. PMID- 11782281 TI - Three new DP alleles identified in a study of 800 unrelated bone marrow donor recipient pairs. AB - HLA-DP genotyping of 800 unrelated donor-recipient pairs in phase 5 of a retrospective analysis of unrelated bone marrow transplantation, sponsored by the National Marrow Donor Program (NMDP), has identified two new DPB1 alleles (DPB1*8701 and DBP1*8801) and one new DPA1 (DPA1*0108) allele. Sequencing confirmed that all three of these new alleles represent novel combinations of previously described sequence motifs, reinforcing the notion that "gene conversion-like" events play an important role in generating HLA allelic diversity. The identification of these new alleles brings the total number of DPA1 alleles to 20 and the total number of DPB1 alleles to 94. PMID- 11782282 TI - Nomenclature for factors of the HLA system, update June 2001. PMID- 11782283 TI - Nomenclature for factors of the HLA system, update July 2001. PMID- 11782284 TI - A model combining cell physiology and population genetics to explain Escherichia coli laboratory evolution. AB - BACKGROUND: Laboratory experiments under controlled conditions during thousands of generations are useful tools to assess the processes underlying bacterial evolution. As a result of these experiments, the way in which the traits change in time is obtained. Under these conditions, the bacteria E. coli shows a parallel increase in cell volume and fitness. RESULTS: To explain this pattern it is required to consider organismic and population contributions. For this purpose we incorporate relevant information concerning bacterial structure, composition and transformations in a minimal modular model. In the short time scale, the model reproduces the physiological responses of the traits to changes in nutrient concentration. The decay of unused catabolic functions, found experimentally, is introduced in the model using simple population genetics. The resulting curves representing the evolution of volume and fitness in time are in good agreement with those obtained experimentally. CONCLUSIONS: This study draws attention on physiology when studying evolution. Moreover, minimal modular models appear to be an adequate strategy to unite these barely related disciplines of biology. PMID- 11782285 TI - A necdin/MAGE-like gene in the chromosome 15 autism susceptibility region: expression, imprinting, and mapping of the human and mouse orthologues. AB - BACKGROUND: Proximal chromosome 15q is implicated in neurodevelopmental disorders including Prader-Willi and Angelman syndromes, autistic disorder and developmental abnormalities resulting from chromosomal deletions or duplications. A subset of genes in this region are subject to genomic imprinting, the expression of the gene from only one parental allele. RESULTS: We have now identified the NDNL2 (also known as MAGE-G) gene within the 15q autistic disorder susceptibility region and have mapped its murine homolog to the region of conserved synteny near necdin (Ndn) on mouse Chr 7. NDNL2/MAGE-G is a member of a large gene family that includes the X-linked MAGE cluster, MAGED1 (NRAGE), MAGEL2 and NDN, where the latter two genes are implicated in Prader-Willi syndrome. We have now determined that NDNL2/Ndnl2 is widely expressed in mouse and human fetal and adult tissues, and that it is apparently not subject to genomic imprinting by the PWS/AS Imprinting Center. CONCLUSION: Although NDNL2/MAGE-G in the broadly defined chromosome 15 autistic disorder susceptibility region, it is not likely to be pathogenic based on its wide expression pattern and lack of imprinted expression. PMID- 11782287 TI - Prenatal diagnosis of Caudal Regression Syndrome : a case report. AB - BACKGROUND: Caudal regression is a rare syndrome which has a spectrum of congenital malformations ranging from simple anal atresia to absence of sacral, lumbar and possibly lower thoracic vertebrae, to the most severe form which is known as sirenomelia. Maternal diabetes, genetic predisposition and vascular hypoperfusion have been suggested as possible causative factors. CASE PRESENTATION: We report a case of caudal regression syndrome diagnosed in utero at 22 weeks' of gestation. Prenatal ultrasound examination revealed a sudden interruption of the spine and "frog-like" position of lower limbs. Termination of pregnancy and autopsy findings confirmed the diagnosis. CONCLUSION: Prenatal ultrasonographic diagnosis of caudal regression syndrome is possible at 22 weeks' of gestation by ultrasound examination. PMID- 11782286 TI - Effect of paper quality on the response rate to a postal survey: a randomised controlled trial. ISRCTN 32032031. AB - BACKGROUND: Response rates to surveys are declining and this threatens the validity and generalisability of their findings. We wanted to determine whether paper quality influences the response rate to postal surveys METHODS: A postal questionnaire was sent to all members of the British Society of Gynaecological Endoscopy (BSGE). Recipients were randomised to receiving the questionnaire printed on standard quality paper or high quality paper. RESULTS: The response rate for the recipients of high quality paper was 43/195 (22%) and 57/194 (29%) for standard quality paper (relative rate of response 0.75, 95% CI 0.33-1.05, p = 0.1 CONCLUSION: The use of high quality paper did not increase response rates to a questionnaire survey of gynaecologists affiliated to an endoscopic society. PMID- 11782288 TI - Effects of de-industrialization on unemployment, re-employment, and work conditions in a manufacturing workforce. AB - BACKGROUND: The purpose of this study was to investigate the impact of a 20-year process of de-industrialization in the British Columbia (BC) sawmill industry on labour force trajectories, unemployment history, and physical and psychosocial work conditions as these are important determinants of health in workforces. METHODS: The study is based on a sample of 1,885 respondents all of whom were sawmill workers in 1979, a year prior to commencement of de-industrialization and who were followed up and interviewed approximately 20 years later. RESULTS: Forty percent of workers, 64 years and under, were employed outside the sawmill sector at time of interview. Approximately one third of workers, aged 64 and under, experienced 25 months of more of unemployment during the study period. Only, 1.5% of workers were identified as a "hard core" group of long-term unemployed. Workers re-employed outside the sawmill sector experienced improved physical and psychosocial work conditions relative to those employed in sawmills during the study period. This benefit was greatest for workers originally in unskilled and semi-skilled jobs in sawmills. CONCLUSIONS: This study shows that future health studies should pay particular attention to long-term employees in manufacturing who may have gone through de-industrialization resulting in exposures to a combination of sustained job insecurity, cyclical unemployment, and adverse physical and psychosocial work conditions. PMID- 11782289 TI - Isolation and characterization of a novel lepidopteran-selective toxin from the venom of South Indian red scorpion, Mesobuthus tamulus. AB - BACKGROUND: Scorpion venom contains insect and mammal selective toxins. We investigated the venom of the South Indian red scorpion, Mesobuthus tamulus for the purpose of identifying potent insecticidal peptide toxins. RESULTS: A lepidopteran-selective toxin (Buthus tamulus insect toxin; ButaIT) has been isolated from this venom. The primary structure analysis reveals that it is a single polypeptide composed of 37 amino acids cross-linked by four disulfide bridges with high sequence homology to other short toxins such as Peptide I, neurotoxin P2, Lqh-8/6, chlorotoxin, insectotoxin I5A, insect toxin 15 and insectotoxin I1. Three dimensional modeling using Swiss automated protein modeling server reveals that this toxin contains a short alpha-helix and three antiparallel beta-strands, similar to other short scorpion toxins. This toxin is selectively active on Heliothis virescens causing flaccid paralysis but was non toxic to blowfly larvae and mice. CONCLUSION: This is the first report of a Heliothine selective peptide toxin. Identification of diverse insect selective toxins offer advantages in employing these peptides selectively for pest control. PMID- 11782290 TI - Manipulation of gene expression by an ecdysone-inducible gene switch in tumor xenografts. AB - BACKGROUND: Rapid, robust and reversible induction of transgene expression would significantly facilitate cancer gene therapy as well as allow the in vivo functional study of newly discovered genes in tumor formation and progression. The popularity of the ecdysone inducible gene switch system has led us to investigate whether such a system can successfully regulate gene expression in a syngeneic tumor system in vivo. RESULTS: MBT-2 and Panc02 carcinoma cells were transfected with components of a modification of the ecdysone switch system driving firefly luciferase (F-Luc). In vitro luciferase expression +/- ecdysone analog GS-E indicated a robust induction with minimal baseline activity and complete decay after 24 hours without drug. In vitro selection of MBT-2 transfected cell clones which had complete absence of F-Luc expression in the absence of stimulation but which expressed this gene at high levels in response to GS-E were chosen for in vivo evaluation. Tumors from engineered MBT-2 cells were grown to 5 mm in diameter prior to GS-E administration, animals euthanized and tumors removed at 6, 12 and 24 hours after GS-E administration and assayed for F-Luc activity. GS-E resulted in a maximal induction of F-Luc activity at 6 hours in tumor tissue with almost complete reversion to control levels by 12 hours. CONCLUSIONS: This study is the first demonstration that robust and reversible transgene expression in tumors is feasible using the ecdysone system, allowing future rapid in vivo functional characterization of gene function or gene therapy applications. PMID- 11782291 TI - Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation. AB - BACKGROUND: Transgenic mice have been used extensively to analyze gene function. Unfortunately, traditional transgenic procedures have only limited use in analyzing alleles that cause lethality because lines of founder mice cannot be established. This is frustrating given that such alleles often reveal crucial aspects of gene function. For this reason techniques that facilitate the generation of embryos expressing such alleles would be of enormous benefit. Although the transient generation of transgenic embryos has allowed limited analysis of lethal alleles, it is expensive, time consuming and technically challenging. Moreover a fundamental limitation with this approach is that each embryo generated is unique and transgene expression is highly variable due to the integration of different transgene copy numbers at random genomic sites. RESULTS: Here we describe an alternative method that allows the generation of clonal mouse embryos harboring a single-copy transgene at a defined genomic location. This was facilitated through the production of Hprt negative embryonic stem cells that allow the derivation of embryos by tetraploid embryo complementation. We show that targeting transgenes to the hprt locus in these ES cells by homologous recombination can be efficiently selected by growth in HAT medium. Moreover, embryos derived solely from targeted ES cells containing a single copy LacZ transgene under the control of the alpha-myosin heavy chain promoter exhibited the expected cardiac specific expression pattern. CONCLUSION: Our results demonstrate that tetraploid embryo complementation by F3 hprt negative ES cells facilitates the generation of transgenic mouse embryos containing a single copy gene at a defined genomic locus. This approach is simple, extremely efficient and bypasses any requirement to generate chimeric mice. Moreover embryos generated by this procedure are clonal in that they are all derived from a single ES cell lines. This facilitates the comparative analysis of lethal alleles and thereby advances our ability to analyze gene function in mammals. PMID- 11782292 TI - Pervasive influence of large-scale climate in the dynamics of a terrestrial vertebrate community. AB - BACKGROUND: Large-scale climatic variability has been implicated in the population dynamics of many vertebrates throughout the Northern Hemisphere, but has not been demonstrated to directly influence dynamics at multiple trophic levels of any single system. Using data from Isle Royale, USA, comprising time series on the long-term dynamics at three trophic levels (wolves, moose, and balsam fir), we analyzed the relative contributions of density dependence, inter specific interactions, and climate to the dynamics of each level of the community. RESULTS: Despite differences in dynamic complexity among the predator, herbivore, and vegetation levels, large-scale climatic variability influenced dynamics directly at all three levels. The strength of the climatic influence on dynamics was, however, strongest at the top and bottom trophic levels, where density dependence was weakest. CONCLUSIONS: Because of the conflicting influences of environmental variability and intrinsic processes on population stability, a direct influence of climate on the dynamics at all three levels suggests that climate change may alter stability of this community. Theoretical considerations suggest that if it does, such alteration is most likely to result from changes in stability at the top or bottom trophic levels, where the influence of climate was strongest. PMID- 11782293 TI - Functional evolution of two subtly different (similar) folds. AB - BACKGROUND: The function of proteins is a direct consequence of their three dimensional structure. The structural classification of proteins describes the ways of folding patterns all proteins could adopt. Although, the protein folds were described in many ways the functional properties of individual folds were not studied. RESULTS: We have analyzed two beta-barrel folds generally adopted by small proteins to be looking similar but have different topology. On the basis of the topology they could be divided into two different folds named SH3-fold and OB fold. There was no sequence homology between any of the proteins considered. The sequence diversity and loop variability was found to be important for various binding functions. CONCLUSIONS: The function of Oligonucleotide/oligosaccharide binding (OB) fold proteins was restricted to either DNA/RNA binding or sugar binding whereas the Src homology 3 (SH3) domain like proteins bind to a variety of ligands through loop modulations. A question was raised whether the evolution of these two folds was through DNA shuffling. PMID- 11782294 TI - Oral health behavior patterns among Tanzanian university students: a repeat cross sectional survey. AB - PURPOSE: This study examines oral health behavioral trends and the development of sociodemographic differences in oral health behaviors among Tanzanian students between 1999 and 2000. METHODS: The population targeted was students attending the Muhimbili University College of Health Sciences (MUCHS) at the University of Dar es Salaam (UDSM), Dar es Salaam, Tanzania. Cross-sectional surveys were conducted and a total of 635 and 981 students, respectively, completed questionnaires in 1999 and 2001. RESULTS: Cross-tabulation analyses revealed that in 1999, the rates of abstinence from tobacco use, and of soft drink consumption, regular dental checkups, and intake of chocolate/candy were 84%, 51%, 48%, and 12%, respectively, among students of urban origin and 83%, 29%, 37%, and 5% among their rural counterparts. The corresponding rates in 2001 were 87%, 56%, 50%, and 9% among urban students and 84%, 44%, 38%, and 4% among rural ones. Multiple logistic regression analyses controlling for sex, age, place of origin, educational level, year of survey, and their interaction terms revealed a significant increase in the rate of soft drink consumption, implementation of oral hygiene measures, and abstinence from tobacco use between 1999 and 2001. Social inequalities observed in 1999, with urban students being more likely than their rural counterparts to take soft drinks and go for regular dental checkups, had leveled off by 2001. CONCLUSION: This study provides initial evidence of oral health behavioral trends, that may be utilized in the planning of preventive programs among university students in Tanzania. PMID- 11782296 TI - [Study on the intestinal microbial colonization resistance in patients with chronic severe hepatitis]. AB - OBJECTIVE: To investigate the changes of microbial colonization resistance of the bowel in patients with chronic severe hepatitis. METHODS: The fecal flora bifidobacteria, enterobacteriaceae, enterococci, and yeasts of subjects (chronic severe hepatitis, chronic hepatitis, and healthy volunteers) were quantitatively and qualitatively analyzed by Mitsuoka's methods. While the ratio of bifidobacterium to enterobacteriaceae ( B/E ratio ) was calculated. RESULTS: The number of bifidobacteria and the B/E ratio in chronic severe hepatitis group was significantly deceased compared with that of the control group (P<0.001). The number of enterobacteriaceae and yeasts was significantly increased compared with that of control group (P<0.001 and P<0.01, respectively). CONCLUSIONS: The results suggest that the intestinal microbial colonization resistance in patients with chronic severe hepatitis is seriously impaired. PMID- 11782295 TI - [Imaging evaluation and interventional therapy of hepatic metastases from small intestinal leiomyosarcoma]. AB - OBJECTIVE: To evaluate the imaging appearances and the short-term curative effect of hepatic metastases from small intestine leiomyosarcoma treated by interventional methods. METHODS: Seven cases with 46 lesions of hepatic metastases from small intestinal leiomyosarcoma were analyzed retrospectively. The diameters of the metastases were from 2 cm to 18 cm. CT triphasic scan and hepatoarterial angiography were performed in all cases. The interventional therapy methods included transcatheter arterial chemoembolization (TACE) (all 7 cases), percutaneous left subclavian artery port-catheter system implantation (PCS) (1 case). Three cases were also treated with percutaneous tumor necrosis drainage (PTND) because of obvious liquefaction necrosis within the tumor. RESULTS: The lesions were substantial occupation and some were mixed density with cystic component. The cystic component increased in the larger tumor. The hepatic metastases were enhanced remarkably during the hepatic arterial-dominant phase scan and had abundant tumor vascular and tumor stain on hepatoarterial angiography. The size of tumor in 4 cases was reduced after TACE. The tumor in the patient who was treated with PCS had no changed. The size of the tumor in 3 cases was slightly enlarged. The tumors in the 3 patients treated with PTND were reduced remarkably. CONCLUSIONS: The predominant blood-supply of the hepatic metastases from small intestinal leiomyosarcoma is the hepatic artery abundant in blood vessels. TACE, PCS and PTND are effective methods to treat hepatic metastases from small intestinal leiomyosarcoma. PMID- 11782297 TI - [Significance of lung perfusion scanning with technetium labeled macroaggregated albumin and pulmonary function assay for diagnosis of early hepatopulmonary syndrome]. AB - OBJECTIVE: To evaluate the values of pulmonary function assay and dynamic pulmonary perfusion imaging with technetium labeled macroaggregated albumin ((99m)TcMAA) in the early diagnosis of hepatopulmonary syndrome (HPS). METHODS: The pulmonary function assay and (99m)TcMAA scans were performed in 28 patients with HPS, 30 cirrhotic patients (CP) without HPS, and 21 healthy controls (HC). RESULTS: In the patients with HPS, PaO(2), SaO(2) and diffusion capacity for carbon monoxide of lungs (DLco) was significantly lower than that in CP (P<0.01) and HC (P<0.01), and alveolar-arterial gradient [P((A-a))O(2)] was significantly increased (P<0.001). Results from (99m)TcMAA scans showed that the radionuclides were distributed over the spleen, kidney, liver and brain, and the ratios of arterivenous shunt were significantly higher than that in CP (P<0.001) and NC (P<0.001). In cirrhotic patients, DLco significantly decreased (P<0.05), P((A a))O(2) and shunt ratios increased (P<0.01 and 0.001). CONCLUSIONS: Pulmonary function assay and dynamic pulmonary perfusion imaging with (99m)TcMAA are sensitive methods for diagnosis of the early HPS. PMID- 11782298 TI - [Accurate diagnosis of stages of hepatic fibrosis by measuring levels of serum hyaluronic acid, procollagen type III, and collagen type IV]. AB - OBJECTIVE: To study the accurate diagnosis of various stages of hepatic fibrosis by measuring serum hyaluronic acid (HA), procollagen type III (PC III), and collagen type IV (CIV). METHODS: The concentrations of serum HA, PC III, CIV in 253 patients with chronic liver disease were measured by radioimmunoassay. Liver biopsies were performed in all of the patients at the same time. According to the results of liver pathological diagnosis, we assessed the ability of serum HA, PC III and CIV to identify correctly patients with hepatic fibrosis (staging >or=S(2)) or cirrhosis (S(4)). RESULTS: The cutoff value of HA, PC III and C IV to identify correctly patients with hepatic fibrosis was 90 microg/L, 90 microg/L, 75 microg/L respectively. The sensitivity (Se) was 80.4%, 82%, 63.1%; the specificity (Spe) was 70.2%, 60.8%, 83.8%; the positive prediction value (PPV) was 86.7%, 83.5%, 90.4%; the negative prediction value (NPV) was 59.8%, 58.4%, 48.4%, respectively. The cutoff value to identify patients with cirrhosis was: HA 210 microg/L, Se 96.2%, Spe 85.3%, PPV 65.4%, NPV 98.8%; PC III 150 microg/L, Se 76.4%, Spe 68.7%, PPV 40.4%, NPV 91.3%; C IV 90 microg/L, Se 80%, Spe 75.8%, PPV 47.8%, NPV 93.2%, respectively. CONCLUSIONS: The determination of serum HA, PC III and C IV can make relatively accurate diagnosis to various stages of hepatic fibrosis. HA is the best for diagnosis of liver cirrhosis. PMID- 11782299 TI - [Role of tumor necrosis factor receptor 1 and Fas antigen in hepatocellular apoptosis of viral hepatitis B patients]. AB - OBJECTIVE: To evaluate the role of tumor necrosis factor receptor 1 (TNFR1) and Fas antigen in hepatocellular apoptosis and necrosis in viral hepatitis B. METHODS: Seventy paraffin sections from patients with HBV infection were studied. Five cases of normal liver tissues were studied as control. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). TNFR1 and Fas antigen were determined by immunohistochemistry. RESULTS: Hepatocellular apoptosis and the expression of TNFR 1 and Fas antigen on hepatocytes were not detected in normal liver tissues. In contrast, there was a strong reaction in TUNEL assay and TNFR1 or Fas antigen expressed on hepatocytes in liver tissues infected with HBV. The degree of apoptosis and the expression of TNFR 1 or Fas antigen on hepatocytes had distinct difference in different hepatitis (P<0.005). There was a positive correlation between degrees of the expression of Fas and hepatic apoptosis (P<0.005), but the similar result was not observed in the expression of TNFR 1 and hepatocellular apoptosis. Our observations also showed that TNFR1 was detected in cytoplasm and cell membrane similarly, and Fas antigen was mainly detected in cytoplasm. There was not positive correlation between degrees of the expression of TNFR1 and Fas antigen on hepatocytes. It was showed that 60.9% (28/46) hepatocytes with strong reaction in TUNEL assay expressed both TNFR1 and Fas antigen. CONCLUSIONS: The degrees of hepatocellular apoptosis and necrosis induced by Fas antigen are stronger than that induced by TNF. The expression of Fas and TNFR 1 on hepatocytes simultaneously may enhance hepatocellular apoptosis in hepatitis B patients. PMID- 11782300 TI - [Pathological changes between HBeAg and anti-HBe in patients with chronic hepatitis B]. AB - OBJECTIVE: To observe the differences of pathological changes between HBeAg and anti-HBe in chronic hepatitis B. METHODS: Liver biopsy was performed in patients with chronic hepatitis B. The histopathological grading and staging were carried out. Serum markers of viral hepatitis were tested. RESULTS: (1) The histopathological grading and staging were closely correlated with the appearance of serum HBeAg and anti-HBe. The number of G(3-4) and S(3-4) in anti-HBe cases was significantly higher than that of G(1-2) and S(1-2), respectively. The number of G(1-2) and S(1-2) in HBeAg cases was significantly higher than that of G(3-4) and S(3-4), respectively. Significant differences were found between the group of anti-HBe cases and the group of HBeAg cases (P<0.005). (2) HBV DNA was detected in 126 of 151 HBeAg positive patients (83.4%), and the positive rate of HBV DNA in anti-HBe positive patient was 29% only. CONCLUSIONS: (1) Severe inflammatory, necrosis and fibrosis of hepatic tissue are observed in patients with anti-HBe positive chronic hepatitis B. (2) Although HBV DNA is positively correlated to HBeAg, HBV-DNA can be detected in part of anti-HBe positive patients. PMID- 11782301 TI - [Influence of staphylococcal enterotoxin A on immunogenicity of hepatocellular carcinoma cells]. AB - OBJECTIVE: To transduce the gene of staphylococcal enterotoxin A (SEA) into a HCC cell line HHCC and to make the cells to express the molecules of SEA for the purpose of improving the immunogenicity and inducing immune rejection of HCC. METHODS: Construct retroviral vector containing the gene of SEA and transduce it into HHCC cells. Then the integration, transcription and expression of recombinant were analyzed. At last cytotoxicity test of peripheral blood mixed lymphocytes was carried out. RESULTS: We obtained the retroviral vector pLXSN SEA, transduced into HHCC cells and obtained the HCC cell line that expressed SEA toxin protein. The content of SEA in supernatant was at the level of pg. The cytotoxicity of HHCC transduced with SEA by T lymphocytes was 45.6%, which was higher than that of HHCC (20.7%). The Km value of T lymphocytes against HHCC transduced with SEA and without SEA was 5.18 x 10(4) and 2.92 x 10(5), separately. The difference had statistical significance. CONCLUSIONS: After transducing the SEA gene, although tiny quantity of expression is detected, the cytotoxicity assay proves that the expression of SEA lead to a robust immune response. PMID- 11782302 TI - [Construction of a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma tissue]. AB - OBJECTIVE: To construct a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma (HCC) tissue. METHODS: Using the suppression subtractive hybridization (SSH), a novel technique has been described recently. cDNA fragments of missing or low expressing tumor suppressor genes in HCC tissue were isolated using paracancerous normal liver tissue and HCC tissue as targets. Then these cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of E.coli by high voltage electroperforation. One hundred positive bacteria clones were randomly picked and identified using enzyme restriction method. RESULTS: The amplified library contained more than 4,000 positive bacteria clones. Random analysis of 100 clones with enzyme restriction method showed that all clones contained 200-600 bp inserts. CONCLUSIONS: A subtracted cDNA library of differentially expressed genes in human normal liver tissue and HCC tissue is constructed successfully with SSH and T/A cloning techniques. The library is efficient and lays solid foundation for screening and cloning new and specific missing or low expressing tumor suppressor genes of HCC. PMID- 11782303 TI - [Changes of the expression of integrin alpha6beta1 and the activity of focal adhesion kinase in the liver sinusoidal endothelial cell in experimental fibrotic rats]. AB - OBJECTIVE: To investigate the expression of integrin alpha(6)beta(1) and the activity of focal adhesion kinase (FAK) in liver sinusoidal endothelial cells (SECs) from experimental fibrotic rats induced by CCl(4). METHODS: By in situ collagenase perfusion and two-step Percoll gradient centrifugation, SECs were isolated and cultured from normal and CCl(4) -treated Wistar rats. The expression of integrin alpha(6)beta(1) was determined by cell-ELISA, and the activity of FAK was assessed by immunoprecipitation-tyrosine kinase assay. RESULTS: The integrin alpha(6)beta(1) was almost absent in the normal SECs and was up-regulated during the fibrotic process; SECs from experimental fibrotic rats possessed higher expression level of integrin alpha(6)beta(1) than normal SECs (P<0.05). The FAK activity in SECs from experimental fibrotic rats increased significantly as compared with the normal controls (P<0.05). CONCLUSIONS: The expression of integrin alpha(6)beta(1) on SECs and the increase of FAK in SECs may be important in the phenotype and function changes of SECs during hepatic fibrogenesis. PMID- 11782304 TI - [Differences of nitric oxide synthase expression and activity between splanchnic arterial and venous vessels of cirrhotic rats]. AB - OBJECTIVE: To understand the implication of differences of nitric oxide synthase (NOS) expression and activity between splanchnic arterial and venous vessels in the pathogenesis of portal hypertension. METHODS: Cirrhosis was induced in 100 Wistar rats by subcutaneously administration of carbon tetrachloride. NOS localization, activity and gene expression in the mesenteric artery and the portal vein vessels of both cirrhotic and normal rats were investigated by immunohistochemistry, chemoluminescence and reverse transcription-polymerase chain reaction, respectively. RESULTS: There was inducible NOS enzyme isoform in al1 layers of splanchnic vessels of cirrhotic rats, whereas endothelial NOS isoform largely in vascular endothelia. NOS activity and its mRNA expression all were significantly increased in cirrhotic rats when compared with normal rats (P<0.05 or 0.01).Moreover, the activities of general and constitutive NOS and the expression of endothelial NOS mRNA in cirrhotic rats were significantly higher in the mesenteric artery than in the portal vein (P<0.01). CONCLUSIONS: Enhanced expression and activity of endothelial NOS enzyme isoform may be mainly responsible for increased NO production of splanchnic vessels in cirrhotic rats, and the differences of NOS expression and activity between the mesenteric artery and the portal vein vessels may be one of the pathogeneses of portal hypertension in which NO might be involved. PMID- 11782305 TI - [Different serum lipid adjustment drugs for the treatment of hyperlipidemic fatty liver]. AB - OBJECTIVE: To research the effect of different serum lipid adjustment drugs, Simvastatin and Fenofibrate, on hyperlipidemic fatty liver. METHODS: The rat models of hyperlipidemic fatty liver induced by high fat diet were treated with Fenofibrate and Simvastatin respectively to investigate the change of the liver index, liver function, the serum and liver lipid, MDA, and pathologic histology. RESULTS: The liver index and the content of triglyceride (TC1.80 +/-0.20/2.10+/ 0.33), total cholesterol (TG 0.76+/-0.18/1.09+/-0.31), MDA both in the serum and the liver in the model group were significantly higher than those in control group. Slight or moderate hepatic steatosis was observed in model group. Fenofibrate decreased serum triglyceride, total cholesterol, and MDA both in serum and liver significantly, but increased the ALT, ALP, liver index, liver lipids, and finally leading to severe hepatic steatosis. Simvastatin lowered the level of lipid and MDA both in serum and liver, and liver histology was improved nearly to normal. Moreover, little side effect on the liver was observed. CONCLUSIONS: Simvastatin can be applied for prevention and treatment of hyperlipidemic fatty liver safely and effectively, while Fenofibrate can not. PMID- 11782306 TI - Quality control of receptor-kinase signaling complexes. AB - The erythropoietin receptor transduces signals leading to the growth, differentiation, and survival of red blood cell precursors via interaction with Janus kinase 2 (JAK2). This interaction was thought to occur only at the plasma membrane. Recent evidence, however, shows that JAK2 assembles with newly synthesized erythropoietin receptors in the endoplasmic reticulum, and that this assembly is essential for efficient expression of the receptors at the cell surface. PMID- 11782307 TI - Regulating sister chromatid separation by separase phosphorylation. AB - A recent paper in Cell highlights a second mechanism of regulation of separase in addition to the bound inhibitor securin. This second pathway involves separase phosphorylation and is dependent on CDC2. PMID- 11782308 TI - Cytokinesis: closing in on the central spindle. AB - The central spindle is important for the completion of cytokinesis. Genetic and biochemical approaches have identified a tetrameric complex, made up of a mitotic kinesin-like protein and a Rho-GTPase activating protein, that mediates central spindle assembly. PMID- 11782309 TI - Membrane-associated MMP regulators: novel cell adhesion tumor suppressor proteins? AB - Matrix metalloproteinases are enzymes that regulate tissue behavior by interactions with extracellular matrix proteins. RECK, a membrane-anchored inhibitor of MMPs was recently characterized for its role in development, tissue homeostasis, and for tumor angiogenesis. PMID- 11782310 TI - Model organisms as a guide to mammalian aging. AB - Recent studies on aging in model systems such as yeast and roundworms have revealed conserved regulation of the process in response to nutrient availability and specific genes that appear to mediate this regulation. Here we review these findings with a focus on the nematode Caenorhabditis elegans and the budding yeast Saccharomyces cerevisiae and highlight general features of the regulation of aging that may have implications for mammals. PMID- 11782311 TI - Plant development meets cell proliferation in Madrid. AB - Cell division is intimately intertwined with plant development, and the mechanisms that link the control of cell proliferation and differentiation with the processes of organogenesis, morphogenesis, and growth are starting to be understood. A recent Juan March meeting explored this interface, and revealed a rich seam of exciting work that is leading toward an integrated view of the role of cell proliferation in the unfolding of developmental programs. PMID- 11782312 TI - Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2. AB - We demonstrate that Rca1 is an essential inhibitor of the anaphase-promoting complex/cyclosome (APC) in Drosophila. APC activity is restricted to mitotic stages and G1 by its activators Cdc20-Fizzy (Cdc20(Fzy)) and Cdh1-Fizzy-related (Cdh1(Fzr)), respectively. In rca1 mutants, cyclins are degraded prematurely in G2 by APC-Cdh1(Fzr)-dependent proteolysis, and cells fail to execute mitosis. Overexpression of Cdh1(Fzr) mimics the rca1 phenotype, and coexpression of Rca1 blocks this Cdh1(Fzr) function. We show that Rca1 and Cdh1(Fzr) are in a complex that also includes the APC component Cdc27. Previous studies have shown that phosphorylation of Cdh1 prevents its interaction with the APC. Our data reveal a different mode of APC regulation by Rca1 at the G2 stage, when low Cdk activity is unable to inhibit Cdh1(Fzr) interaction. PMID- 11782313 TI - Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. AB - A late step in cytokinesis requires the central spindle, which forms during anaphase by the bundling of antiparallel nonkinetochore microtubules. Microtubule bundling and completion of cytokinesis require ZEN-4/CeMKLP-1, a kinesin-like protein, and CYK-4, which contains a RhoGAP domain. We show that CYK-4 and ZEN-4 exist in a complex in vivo that can be reconstituted in vitro. The N terminus of CYK-4 binds the central region of ZEN-4, including the neck linker. Genetic suppression data prove the functional significance of this interaction. An analogous complex, containing equimolar amounts of a CYK-4 ortholog and MKLP-1, was purified from mammalian cells. Biochemical studies indicate that this complex, named centralspindlin, is a heterotetramer. Centralspindlin, but not its individual components, strongly promotes microtubule bundling in vitro. PMID- 11782314 TI - A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. AB - The mechanism during apoptosis by which cytochrome c is rapidly and completely released in the absence of mitochondrial swelling is uncertain. Here, we show that two distinct pathways are involved. One mediates release of cytochrome c across the outer mitochondrial membrane, and another, characterized in this study, is responsible for the redistribution of cytochrome c stored in intramitochondrial cristae. We have found that the "BH3-only" molecule tBID induces a striking remodeling of mitochondrial structure with mobilization of the cytochrome c stores (approximately 85%) in cristae. This reorganization does not require tBID's BH3 domain and is independent of BAK, but is inhibited by CsA. During this process, individual cristae become fused and the junctions between the cristae and the intermembrane space are opened. PMID- 11782315 TI - Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor. AB - Nicastrin is genetically linked to Notch/lin-12 signaling in C. elegans and is part of a large multiprotein complex along with Presenilin. Here we describe the isolation and characterization of Drosophila Nicastrin (Nic) mutants. Nic mutants and tissue clones display characteristic Notch-like phenotypes. Genetic and inhibitor studies indicate a function for Nicastrin in the gamma-secretase step of Notch processing, similar to Presenilin. Further, Nicastrin is genetically required for signaling from membrane-anchored activated Notch. In the absence of Nicastrin, Presenilin is destabilized and mature C-terminal subunits are absent. Nicastrin might recruit gamma-secretase substrates into the proteolytic complex as a prerequisite for Presenilin maturation and active complex assembly. PMID- 11782316 TI - Drosophila nicastrin is essential for the intramembranous cleavage of notch. AB - The catalytic subunit of gamma-secretase is thought to be Presenilin, which is required for both the cleavage of APP and in the processing of Notch. Presenilin is found in a multisubunit complex that also contains Nicastrin. Nicastrin has been implicated in APP processing, but its role in Notch signaling remains unclear. Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step. Partially processed Notch accumulates apically in nicastrin and presenilin mutant follicle cells. nicastrin and presenilin mutations also disrupt the spectrin cytoskeleton, suggesting that the gamma-secretase complex has another function in Drosophila in addition to its role in processing Notch and APP. PMID- 11782317 TI - Creation of a Sog morphogen gradient in the Drosophila embryo. AB - A variety of genetic evidence suggests that a gradient of Decapentaplegic (Dpp) activity determines distinct cell fates in the dorsal region of the Drosophila embryo, and that this gradient may be generated indirectly by an inverse gradient of the BMP antagonist Short gastrulation (Sog). It has been proposed that Sog diffuses dorsally from the lateral neuroectoderm where it is produced, and is cleaved and degraded dorsally by the metalloprotease Tolloid (Tld). Here we show directly that Sog is distributed in a graded fashion in dorsal cells and that Tld degradation limits the levels of Sog dorsally. In addition, we find that Dynamin dependent retrieval of Sog acts in parallel with degradation by Tld as a dorsal sink for active Sog. PMID- 11782318 TI - An allelic series at the PDGFalphaR locus indicates unequal contributions of distinct signaling pathways during development. AB - A central issue in signal transduction is the physiological contribution of different growth factor-initiated signaling pathways. We have generated knockin mice harboring mutations in the PDGFalpha receptor (PDGFalphaR) that selectively eliminate its capacity to activate PI3 kinase (alpha(PI3K)) or Src family kinases (alpha(Src)). The alpha(PI3K) mutation leads to neonatal lethality due to impaired signaling in many cell types, but the alpha(Src) mutation only affects oligodendrocyte development. A third knockin line containing mutations that eliminate multiple docking sites does not increase the severity of the alpha(PI3K) mutation. However, embryos with mutations in the PI3K binding sites of both PDGFRs (alpha and beta) recapitulate the PDGFalphaR null phenotype. Our results indicate that PI3K has a predominant role in PDGFalphaR signaling in vivo and that RTK-activated signaling pathways execute both specific and overlapping functions during mammalian development. PMID- 11782319 TI - Ectodermal syndecan-2 mediates left-right axis formation in migrating mesoderm as a cell-nonautonomous Vg1 cofactor. AB - Heparan sulfate proteoglycans expressed on the Xenopus animal cap ectoderm have been implicated in transmitting left-right information to heart and gut primordia. We report here that syndecan-2 functions in the ectoderm to mediate cardiac and visceral situs, upstream of known asymmetrically expressed genes but independently of its ability to mediate fibronectin fibrillogenesis. Left-right development is dependent on a distinct subset of glycosaminoglycan attachment sites on syndecan-2. A novel in vivo approach with enterokinase demonstrates that syndecan-2 functions in left-right patterning during early gastrulation. We describe a cell-nonautonomous role for ectodermal syndecan-2 in transmitting left right information to migrating mesoderm. The results further suggest that this function may be related to the transduction of Vg1-related signals. PMID- 11782320 TI - Anesthesiology and hyperbaric medicine. PMID- 11782321 TI - Endomyocardial pH and right ventricular ischemia: not just another tool? PMID- 11782322 TI - The oxygen concentrator is a suitable alternative to oxygen cylinders in Nepal. AB - PURPOSE: To review the efficacy and reliability of oxygen concentrators used over the last six years in Nepal. The apparatus used was a DeVilbiss(R) oxygen concentrator that provided O(2) for anesthesia supplemented with compressed air to drive a Penlon Manley Multivent Ventilator(R). It remains difficult to supply oxygen in cylinders to peripheral hospitals in Nepal due to lack of proper roads. METHODS: We conducted a retrospective analysis of a sample of 378 cases anesthetized at the Bir Hospital and at a private hospital in Kathmandu from April through October 1999. The Bain circuit or its modification was used in adults, and Bain or Ayre's T piece in children. High flows from the oxygen concentrator used with the Bain and Ayre's T-circuits were reduced to 2 L/min, delivered through the halothane vaporizer, supplemented by room air in the modified Bain circuit. Positive pressure ventilation was provided with an Ambubag, Oxford Inflating Bellows or Penlon Manley Multivent Ventilator. Blood pressure, electrocardiogram, FiO(2) and SpO(2) were monitored in all cases. RESULTS: Surgery included urologic, general surgery, obstetrics and gynecological procedures, neurosurgery and closed mitral valvotomy. Age ranged from six months to 78 yr. The anesthetic time lasted from 45 min to 12 hr. The FiO(2) ranged from 0.5 to 0.6 in the Bain and Ayre's T circuits, and from 0.34 to 0.40 in the modified Bain circuit with a flow of oxygen of 2 L/min from the concentrator. CONCLUSION: With regular maintenance and servicing done locally, the oxygen concentrator can be used safely in adults and children. Use of the oxygen concentrator is a suitable alternative to oxygen cylinders in the developing world. PMID- 11782323 TI - Titration of isoflurane using BIS index improves early recovery of elderly patients undergoing orthopedic surgeries. AB - PURPOSE: This study was designed to investigate the effect of bispectral index (BIS) monitoring on the recovery profiles, level of postoperative cognitive dysfunction, and anesthetic drug requirements of elderly patients undergoing elective orthopedic surgery with general anesthesia. METHODS: Sixty-eight patients over the age of 60 were randomized into one of two groups. In the standard practice (SP) group, the anesthesiologists were blinded to the BIS value, and isoflurane was titrated according to standard clinical practice. In the BIS group, isoflurane was titrated to maintain a BIS value between 50-60. RESULTS: The total isoflurane usage was 30% lower in the BIS group compared to the SP group (5.6 +/- 3 vs 7.7 +/- 3 mL, P <0.05). The time to orientation was faster in the BIS group compared to the SP group (9.5 +/- 3 vs 13.1 +/- 4 min, P <0.001). There were no differences in the postoperative psychometric tests between the two groups. CONCLUSIONS: There was no difference in the level of postoperative cognitive dysfunction between the two groups. However, titration of isoflurane using the BIS index decreased utilization of isoflurane and contributed to faster emergence of elderly patients undergoing elective knee or hip replacement surgery. PMID- 11782324 TI - Fat embolism syndrome and elective knee arthroplasty. AB - PURPOSE: To report a case of fat embolism syndrome (FES) following elective left knee arthroplasty and review the diagnosis, investigation, prevention and perioperative management of this condition. CLINICAL FEATURES: A 76-yr-old lady presented for left total knee arthroplasty under general anesthesia. After an uneventful anesthetic and initial recovery, she developed respiratory and neurological complications six hours postoperatively necessitating supportive care in the intensive care unit. Following extensive investigation, a clinical diagnosis of FES was made 48 hr postoperatively supported by the development of diffuse encephalopathy, thrombocytopenia, hypoxemia, chest petechiae and chest x ray changes. A magnetic resonance imaging scan five days postoperatively confirmed this diagnosis. Her postoperative course showed gradual improvement consistent with a slowly resolving encephalopathy. Previous published cases of FES associated with knee arthroplasty present either with intraoperative cardiorespiratory collapse or, as with this patient, in the postoperative period with respiratory, cardiovascular and/or cerebral dysfunction. CONCLUSIONS: The clinical diagnosis of FES is essentially one of exclusion, supported by laboratory and radiological investigations. Preoperative identification of at risk patients, use of appropriate invasive perioperative monitoring and modified surgical techniques may minimize the development of the syndrome. Treatment is supportive. PMID- 11782325 TI - Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations. AB - PURPOSE: To compare two protocols of epidural administration of racemic methadone for postoperative analgesia (continuous infusion and intermittent bolus), focussing on plasma concentration, analgesic efficacy and side effects. METHODS: Ninety patients undergoing abdominal or lower-limb surgery were randomly assigned to two groups in a prospective double-blind design. The continuous infusion patients (n=60) received initial doses of 3 to 6 mg followed by 6 to 12 mg by continuous infusion over 24 hr. The bolus administration patients (n=30) received repeated boluses of 3 to 6 mg of racemic methadone every eight hours. Pain intensity was assessed on a visual analog scale. Amount of supplementary analgesia was recorded, as was the incidence of side effects. Plasma methadone concentrations were determined by high performance liquid chromatography. Treatment was continued for 72 hr. RESULTS: Pain relief was good and comparable in both groups throughout the three days of treatment. No accumulation of plasma racemic methadone was observed in either group, although the concentrations were significantly higher in the bolus group. Miosis was significantly more frequent in the bolus group. CONCLUSION: Plasma methadone concentrations were significantly lower with continuous infusion. Plasma methadone accumulation, which is considered the main disadvantage for its purported influence on the incidence of side effects, did not occur at the doses used over the three days of treatment that we report. PMID- 11782326 TI - A systematic review of adjuncts for intravenous regional anesthesia for surgical procedures. AB - PURPOSE: To review the use of adjuncts to intravenous regional anesthesia (IVRA) for surgical procedures in terms of their intraoperative effects (efficacy of block and tourniquet pain) and postoperative analgesia. SOURCE: A systematic search (Medline, Embase, reference lists) for randomized, controlled and double blinded studies using adjuncts to IVRA for surgical procedures was conducted. Data were collected on intraoperative effects (onset/offset and quality of block and tourniquet pain), postoperative effects (pain intensity and analgesic consumption) and side effects recorded. Statistical significance as indicated in the original report and likely clinical relevance were taken into account to arrive at a judgment of overall benefit. PRINCIPAL FINDINGS: Twenty-nine studies met all inclusion criteria. Data on 1,217 study subjects are included. Adjuncts used were opioids (fentanyl, meperidine, morphine, sufentanil), tramadol, non steroidal anti-inflammatory drugs (NSAIDs; ketorolac, tenoxicam, acetyl salicylate), clonidine, muscle relaxants (atracurium, pancuronium, mivacurium), alkalinization with sodium bicarbonate, potassium and temperature. There is good evidence to recommend NSAIDs in general and ketorolac in particular, for improving postoperative analgesia. Clonidine 1 microg/kg also appears to improve postoperative analgesia and prolong tourniquet tolerance. Opioids are poor by this route; only meperidine 30 mg or more has substantial postoperative benefit but at the expense of postdeflation nausea, vomiting and dizziness. Muscle relaxants improve intraoperative motor block and aid fracture reduction. CONCLUSION: Using NSAIDs or clonidine as adjuncts to IVRA improves postoperative analgesia and muscle relaxant improves motor block. PMID- 11782328 TI - Examining the evidence in anesthesia literature: a survey and evaluation of obstetrical postdural puncture headache reports. AB - PURPOSE: To describe a bibliographic database on the literature of postdural puncture headache (PDPH) in the obstetrical population, to describe the research architecture in this field, and to evaluate the quality of case-control studies, cohort studies, and controlled clinical trials on PDPH. METHODS: Computerized bibliographic searches, citation review, and hand searches were conducted to find all relevant citations on incidence, clinical course, prevention, or treatment of PDPH in parturients. The study design and topic(s) covered by each study were evaluated. Case-control studies and cohort studies were evaluated using the Quality Index; clinical trials were evaluated using the Jadad scale. RESULTS: One hundred ninety-six relevant citations were published between 1949 and 1999. Research on PDPH has been increasing rapidly with the majority of studies published in the 1990's. Incidence and prevention were the focus of over half of all citations. Optimal study designs were infrequently utilized. The methodological quality was poor for observational studies (Quality Index 10/29) and clinical trials (Jadad scale 2/5). CONCLUSION: Although the amount of research on PDPH in parturients is increasing, use of optimal study designs and improvement in methodology is needed. PMID- 11782329 TI - Addition of bupivacaine 1.25 mg to fentanyl confers no advantage over fentanyl alone for intrathecal analgesia in early labour. AB - PURPOSE: a) To evaluate the effect of adding 1.25 mg of bupivacaine to intrathecal fentanyl on the duration of analgesia in an Asian population and b) to examine if the baricity of the local anesthetic at this dose has any bearing on the duration and quality of block. METHODS: Forty-eight parturients in early labour received combined spinal epidural (CSE) analgesia to evaluate a) the effect of adding 1.25 mg of bupivacaine to intrathecal (IT) fentanyl 25 microg on the duration of analgesia and b) the effect of baricity of intrathecal local anesthetic on the duration and quality of the block. Patients were randomly allocated to receive: IT fentanyl 25 microg plus normal saline (Group f, n=16), IT fentanyl 25 microg plus plain bupivacaine 1.25 mg (Group f+pb, n=16) and IT fentanyl 25 microg plus heavy bupivacaine 1.25 mg (Group f+hb, n=16). The two components of the IT injectate (total of 2.25 mL) were given sequentially. RESULTS: Group f+hb had the lowest sensory dermatomal block (T7 vs T4 (Group f), T5 (Group f+pb), P <0.01). There were no differences in the duration of analgesia and incidence of side effects among the groups. CONCLUSION: We found no advantage of adding 1.25 mg bupivacaine to fentanyl 25 microg. At this dose, the baricity of bupivacaine has no effect on the duration of analgesia. PMID- 11782330 TI - Sevoflurane inhibits contraction of uterine smooth muscle from pregnant rats similarly to halothane and isoflurane. AB - PURPOSE: The present study was designed to clarify the direct effects of the volatile anesthetics halothane, isoflurane and sevoflurane on oxytocin-induced uterine smooth muscle contraction from pregnant rats. METHODS: Longitudinal smooth muscle layers were obtained from pregnant rats. Intracellular concentration of free Ca++ ([Ca++](i)) was measured, using a fluorescence technique, simultaneously with muscle tension. Inward Ba++ current (I(Ba)) through voltage-dependent Ca++ channels (VDCCs) was measured using a whole cell patch clamp technique. After incubation with 20 nM oxytocin, halothane, isoflurane or sevoflurane (1, 2, and 3%) was introduced into the tissue bath. RESULTS: All volatile anesthetics significantly inhibited muscle contraction concomitant with a decrease in [Ca++](i). Volatile anesthetics also inhibited the peak I(Ba). When the anesthetic concentrations were expressed as multiples of minimum alveolar concentrations, there were no differences in the inhibitory potencies of the three volatile agents tested for muscle tension and VDCC. CONCLUSIONS: Volatile anesthetics halothane, isoflurane and sevoflurane reduce the oxytocin-induced contraction of pregnant uterine smooth muscle. Inhibition of the contraction by the volatile anesthetics is due, at least in part, to the decrease in [Ca++](i), and the decrease in [Ca++](i) may be mediated by inhibition of VDCC activity. PMID- 11782331 TI - Lidocaine with fentanyl, compared to morphine, marginally improves postoperative epidural analgesia in children. AB - PURPOSE: To compare the epidural administration of fentanyl (1 microg/mL) combined with lidocaine 0.4% to preservative-free morphine for postoperative analgesia and side effects in children undergoing major orthopedic surgery. METHODS: In a prospective, double-blind study, 30 children, ASA I-II, 2-16-yr old, were randomly allocated to receive immediately after surgery either epidural F-L (epidural infusion at a rate of 0.1-0.35 mL/kg/hr of 1 microg/mL of fentanyl and lidocaine 0.4%) or epidural M (bolus of 20 microg/kg of morphine in 0.5 mL/kg saline every eight hours). Both groups received 40 mg/kg of iv metamizol (dipyrone) every six hours. In the F-L Group, blood samples were taken on the second and third postoperative day to determine total lidocaine concentrations. Adequacy of analgesia using adapted pediatric pain scales (0-10 score) and side effects were assessed every eight hours postoperatively. RESULTS: Resting pain scores were under 4, 95% of the time in the F-L Group and 87% of the time in the M Group (Chi square=4.674, P <0.05). The frequency of complications was very similar in both groups. The F-L Group total plasma lidocaine concentrations were directly related to the dose received, and below the toxic range in all patients. CONCLUSIONS: Postoperative epidural fentanyl with lidocaine infusion provides slightly better analgesia than conventional bolus administration of epidural morphine. Side-effects or risk of systemic toxicity were not augmented by the addition of lidocaine to epidural opioids. PMID- 11782332 TI - Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia. AB - PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups. PMID- 11782333 TI - Anesthetic management for a patient with Jansky-Bielschowsky disease. AB - PURPOSE: To describe the anesthetic management of a patient with Jansky Bielschowsky disease (JBD), the late infantile form of neuronal ceroid lipofuscinosis, characterized by dementia, severe and drug resistant grand mal, myoclonic seizures, and blindness. CLINICAL FEATURES: A 14-yr-old girl with JBD was scheduled for resection of a gingival tumour and an infected sinus in the sacral area. Her preanesthetic examination revealed extreme muscle atrophy and dementia. Grand mal, myoclonic seizures, and upper airway obstruction were frequent. Following iv induction with thiamylal, anesthesia was maintained with sevoflurane, N(2)O and O(2). Her trachea was intubated without using muscle relaxants. Muscle relaxants were not used during the operation. Apart from an intractable hypothermia, the intraoperative course was uneventful. The emergence of anesthesia was smooth, except for persisting seizures. CONCLUSION: General anesthesia using thiamylal and sevoflurane provided satisfactory conditions during operation in a patient with JBD. Intraoperative hypothermia required particular attention. PMID- 11782334 TI - Epi and endomyocardial pH allows the detection of acute right ventricular ischemia in pigs: a new evaluation method. AB - BACKGROUND: Techniques which identify acute right ventricular (RV) ischemia may help elucidate the pathophysiology of RV dysfunction. This study's goal was to validate an acute RV ischemia or infarction detection technique. Could RV endomyocardial and epimyocardial (interstitial) pH electrodes detect RV pH changes in an animal model of RV infarction produced by right coronary artery ligation? METHODS: In ten adult anesthetized pigs, RV interstitial (pHepi) and transmural endomyocardial pH (pHendo) were measured before and serially after right coronary occlusion. RESULTS: pHendo and pHepi fell significantly following coronary occlusion. The absolute and relative rates of change were greater for pHendo (mean pH decreased from 7.36 to 7.04) compared to pHepi ( mean pH of 7.28 vs 7.08; P <0.002). pH was unchanged in control experiments where the electrode was placed in the right atrial or ventricular chamber, and in sham-operated animals. These data suggest that coronary ligation induced RV ischemia produces RV myocardial pH changes, which can be recorded from an electrode placed against the RV wall via a central vein, or in the interstitium. CONCLUSION: This newly described technique may be helpful in developing more discriminating tools to identify acute RV ischemia. PMID- 11782336 TI - Effective nasotracheal intubation using a modified transillumination technique. AB - PURPOSE: Difficult intubation is a major problem in anesthesia. In case of limited mouth opening only a few intubating devices are available. Our study was designed to evaluate the effectiveness and safety of a modified transillumination technique for nasotracheal intubation (NTI). METHODS: One hundred twenty-three patients needing NTI were studied, 76 in group A: NTI with no expected intubation difficulty; and 47 in group B: limited mouth opening (<20 mm). All intubations were performed with the Trachlight(TM). Patients in group A were under general anesthesia while deep sedation (maintaining spontaneous breathing) was used in patients in group B. The standard transillumination technique was modified by keeping the metallic stylet in place and personalizing the length and the angle of the short arm of the J shaped endotracheal tube-transillumination lightwand (ETT-TL) assembly. RESULTS: The overall rate of success was 98.4% and 92.6% of intubations were successful on the first attempt. The average duration of intubation was 28 sec +/- 15 sec. Success rate and duration of intubation were similar in both groups. CONCLUSION: Modification of the technique facilitated transillumination and placement of the ETT. The simplicity and high success rate of NTI by transillumination with the TL suggest our modified technique is a valuable alternative for NTI in patients with difficult airway. PMID- 11782337 TI - Cerebral arterial gas embolism following diagnostic bronchoscopy: delayed treatment with hyperbaric oxygen. AB - PURPOSE: To describe a clinical scenario consistent with the diagnosis of cerebral arterial gas embolism (CAGE) acquired during an outpatient bronchoscopy. Our discussion explores the mechanisms and diagnosis of CAGE and the role of hyperbaric oxygen therapy. CLINICAL FEATURES: A diagnostic bronchoscopy was performed on a 70-yr-old man who had had a lobectomy for bronchogenic carcinoma three months earlier. During the direct insufflation of oxygen into the right middle lobe bronchus, the patient became unresponsive and developed subcutaneous emphysema. Immediately, an endotracheal tube and bilateral chest tubes were placed with resultant improvement in his oxygen saturation. However, he remained unresponsive with extensor and flexor responses to pain. Later, in the intensive care unit, he exhibited seizure activity requiring anticonvulsant therapy. Sedation was utilized only briefly to facilitate controlled ventilation. Investigations revealed a negative computerized tomography (CT) scan of the head, a normal cerebral spinal fluid examination, a CT chest that showed evidence of barotrauma, and an abnormal electroencephalogram. Fifty-two hours after the event, he was treated for presumed CAGE with hyperbaric oxygen using a modified United States Navy Table 6. Twelve hours later he had regained consciousness and was extubated. He underwent two more hyperbaric treatments and was discharged from hospital one week after the event, fully recovered. CONCLUSION: A patient with presumed CAGE made a complete recovery following treatment with hyperbaric oxygen therapy even though it was initiated after a significant time delay. PMID- 11782338 TI - Intracranial subdural hematoma after unintended durotomy during spine surgery. AB - PURPOSE: To report a case of intracranial subdural hematoma occurring after a spinal dural tear that was made unintentionally during the course of a posterior laminectomy and spinal fusion at the L(5)-S(1) level. The possible physiopathological mechanisms are discussed. CLINICAL FEATURES: On the fourth postoperative day, a 59-yr-old woman displayed persistent headache following unintended durotomy during spine implant revision. Perioperative blood loss was 2840 mL and intravascular replacement was about 3000 mL. She was hydrated with iv fluids and treated with non-steroidal anti-inflammatory drugs. The symptoms improved but persisted. With the aggravation of the headache complicated with unconsciousness and the appearance of focal neurological signs on the eighth day, a computed tomography was obtained and revealed a right subdural hematoma. Following surgical drainage, the patient made an uneventful recovery. CONCLUSION: This case reminds us that subdural hematoma formation can complicate durotomy during spine surgery. Neurological deterioration in the postoperative period should prompt clinicians to rule out the diagnosis and intervene rapidly as appropriate. PMID- 11782341 TI - Cost containment in obstetric analgesia. PMID- 11782342 TI - Thoracoabdominal retroperitoneal lymph node dissection (RPLND) and hemodynamic instability in the postoperative period. PMID- 11782343 TI - Fat embolism and postoperative coagulopathy. PMID- 11782344 TI - Do preoperative anxiety and depression affect quality of recovery and length of stay after hip or knee arthroplasty? PMID- 11782345 TI - Radial artery cannulation in edematous patients. PMID- 11782346 TI - Airway loss during tracheostomy. PMID- 11782348 TI - Inhibition of benzo(a)pyrene-induced lung tumorigenesis in A/J mice by dietary N acetylcysteine conjugates of benzyl and phenethyl isothiocyanates during the postinitiation phase is associated with activation of mitogen-activated protein kinases and p53 activity and induction of apoptosis. AB - Recent studies in cell culture have shown that isothiocyanates (ITCs) induce apoptosis via activation of mitogen-activated protein (MAP) kinases and p53 pathways, suggesting a potential for ITCs or their conjugates to inhibit tumorigenesis during the postinitiation phase. To evaluate whether ITC compounds administered after carcinogen treatment inhibit lung tumorigenesis, we investigated in A/J mice the effects of the N-acetylcysteine (NAC) conjugates of benzyl (BITC-NAC) and phenethyl ITC (PEITC-NAC) in the diet (15 micromol/g) administered after a single dose of 20 micromol benzo(a)pyrene [B(a)P]. The formation of lung adenomas was examined 140 days after B(a)P dosing. Both the BITC-NAC and PEITC-NAC-treated groups showed a significant reduction in lung tumor multiplicity from 6.1 +/- 3.1 tumors/mouse in the B(a)P group fed the control diet to 3.7 +/- 2.9 and 3.4 +/- 2.7 tumors/mouse (P = 0.018 and 0.006, respectively). To investigate the mechanisms of tumor inhibition, lung tissues were obtained at 21, 84, and 140 days at interim sacrifices during the bioassay. These tissues showed a significant increase in apoptosis as determined by in situ end-labeling for both ITC-NAC-treated groups. The MAP kinase pathway was activated in the ITC-NAC-treated groups. The activation of c-Jun NH(2)-terminal kinase was higher in the BITC-NAC and PEITC-NAC groups when compared with B(a)P treated control. The phosphorylation of p38 and extracellular signal-regulated kinases (ErKs) 1 and 2 was also induced by these treatments. To determine the downstream target of MAP kinases, activator protein-1 (AP-1) and nuclear factor kappaB activities were evaluated by gel shift assay. The AP-1 binding activity was remarkably increased in lung tissue from both the BITC-NAC and PEITC-NAC groups. No change in nuclear factor-kappaB binding activity was found, however. Phosphorylation of p53 was also higher than the constitutive levels in both ITC NAC-treated groups, but no induction of p53 expression was detected. This study demonstrates the chemopreventive efficacy of the NAC conjugates of PEITC and BITC administered in the diet after a single dose of B(a)P for lung tumorigenesis and provides the first in vivo evidence that activation of MAP kinases, AP-1 transcription factors, p53 phosphorylation, and the induction of apoptosis may be involved in the chemopreventive activity of these compounds. PMID- 11782349 TI - Systemic tumor suppression by the proapoptotic gene bik. AB - Metastatic breast cancer requires systemic treatment. We have developed a systemic gene therapy approach for breast cancer, consisting of a nonviral gene delivery system (SN) and a proapoptotic gene, bik. The transfection efficiency of SN carrying a reporter gene was 5-10 times higher than the common nonviral agents Fugene-6 and Lipofectamine in the presence of serum. The SN-bik gene complex induced significant apoptosis in four breast cancer cell lines in vitro as well as in orthotopic tumor tissues in nude mice. Systemically administrated SN-bik significantly inhibited the growth and metastasis of human breast cancer cells implanted in nude mice and prolonged the life span of the treated animals. This study demonstrates that SN-bik is a promising approach for further development as a potential therapeutic agent of cancer. PMID- 11782350 TI - Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival. AB - Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. Our results reveal a new hBUB1 missense mutation (Ala130Ser) but not any hBUBR1 coding sequence mutations. hBUB1 and hBUBR1 mRNA levels were reduced to < 10% of the neighboring normal tissues in 3 of 103 and 3 of 109 carcinomas, respectively, and to < 50% in 7 and 7 carcinomas, whereas the overall expression levels were markedly higher in cancers than in normal tissues. Carcinomas with reduced hBUB1 and/or hBUBR1 mRNA levels, as well as the colon carcinoma harboring the hBUB1 mutation, were associated with lymph node metastasis (P < 0.005) and shorter relapse-free survival after surgery (P = 0.006). Thus, hBUB1 and hBUBR1 may contribute to a specific driving force in tumor metastasis and progression as a result of nonmutational, as well as mutational, inactivation. PMID- 11782351 TI - Smac is required for cytochrome c-induced apoptosis in prostate cancer LNCaP cells. AB - Release of cytochrome c from mitochondria to cytosol has been identified as one of the central events of apoptosis. Direct injection of cytochrome c induces apoptosis in some but not in all cell types. We observed that LNCaP prostate cancer cells failed to undergo apoptosis induced by cytochrome c microinjections. Microinjection of cytochrome c with another mitochondrial protein, Smac, was sufficient to activate caspases, however. Smac is believed to function as a neutralizer of caspase inhibitors, and mass spectrometry analysis identified XIAP as a predominant Smac binding protein in LNCaP cells. These findings are consistent with a requirement for a release of Smac from mitochondria to enable caspase activation in prostate cells. Indeed, translocation of Smac from mitochondria to cytosol was observed in LNCaP cells that undergo apoptosis and was inhibited by epidermal growth factor, which is a survival factor for these cells. These results further emphasize the central role of mitochondria in the regulation of apoptosis in prostate cancer cells. PMID- 11782352 TI - Development of spontaneous uterine tumors in low molecular mass polypeptide-2 knockout mice. AB - The presentation of antigenic peptides by MHC class I molecules is important for tumor rejection by CTLs. Such antigenic peptides are generated as a result of the degradation of intracellular proteins by the proteasome pathway, a process that is influenced by the IFN-gamma-inducible low molecular mass polypeptide-2 (LMP2) subunit of the proteasome complex. LMP2 knockout mice thus exhibit a defect in proteasome function. Female LMP2(-/-) mice are now shown to develop uterine neoplasms, with a disease prevalence of approximately 36% by 12 months of age. This observation indicates that proteasome function is essential for MHC class I mediated tumor rejection by CTLs. PMID- 11782353 TI - Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. AB - Accumulating evidence indicates that overproduction of prostanoids attributable to overexpression of cyclooxygenase-2 (COX-2) plays an important role in colon carcinogenesis. We have shown recently that the prostaglandin (PG) E receptor, EP(1), but not EP(3), is involved in mouse colon carcinogenesis. In line with our previous study, here we examined the role of prostanoid receptors in colon carcinogenesis using six additional lines of knockout mice deficient in prostanoid receptors EP(2), EP(4), DP, FP, IP, or TP. The animals were treated with the colon carcinogen, azoxymethane (AOM), and examined for the development of aberrant crypt foci (ACFs), putative preneoplastic lesions in the colon. Formation of ACFs was decreased only in the EP(4)-knockout mice, to 56% of the wild-type level. To confirm these results, we also examined the inhibitory effects of an EP(4)-selective antagonist, ONO-AE2-227, in the diet on the formation of AOM-induced colon ACFs in C57BL/6Cr mice and on the development of intestinal polyps in Min mice. ONO-AE2-227 at a dose of 400 ppm reduced the formation of ACFs to 67% of the control level, and intestinal polyp numbers in Min mice receiving 300 ppm were decreased to 69% of the control level. Plating efficiency assays showed that addition of 1.0 microM ONO-AE1-329, an EP(4) selective agonist, resulted in a 1.8-fold increase in the colony number of the human colon cancer cell line, HCA-7, similar to the effect of PGE(2). Moreover, EP(4) mRNA expression was clearly observed in normal colon mucosa and colon tumors in mice. Our previous and present results indicate that PGE(2) contributes to colon carcinogenesis through its actions mediated through EP(1) and EP(4) receptors; therefore, antagonists for these two receptors may be good candidates as chemopreventive agents against colon cancer. PMID- 11782354 TI - The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15). AB - The nucleoporin gene, NUP98, has been reported to be fused to seven partner genes in hematological malignancies with 11p15 translocations. We report here a novel NUP98 partner gene, HOXD11, not HOXD13, in a pediatric patient with de novo AML having t(2;11)(q31;p15), using a cDNA panhandle PCR. The HOXD11 gene is one of the HOXD cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain. Reverse transcription (RT)-PCR analysis showed that two alternatively spliced 5'-NUP98 transcripts were fused in frame to the HOXD11 gene. Both proteins consist of an NH(2)-terminal phenylalanine-glycine repeat motif of NUP98 and COOH-terminal homeodomain of HOXD11. RT-PCR analysis in various leukemic cell lines showed that expression of the HOXD11 gene was significantly more frequent in BCR-ABL-positive than in BCR-ABL-negative leukemic cell lines (P = 0.028). Our results revealed that t(2;11)(q31;p15) was not a single chromosomal abnormality and that the NUP98-HOXD fusion genes encode similar fusion proteins, which suggests that the NUP98-HOXD11 as well as NUP98 HOXD13 fusion protein play a role in leukemogenesis through similar mechanisms. PMID- 11782355 TI - Mutational analysis of promoters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients: identification of three novel germ-line mutations in promoter of the hMSH2 gene. AB - The human DNA mismatch repair genes hMSH2 and hMLH1 are responsible for the development of hereditary nonpolyposis colorectal cancer (HNPCC). Although genetic alteration of the coding region of hMSH2 and hMLH1 has been well investigated in HNPCC patients, the regulatory regions of these genes have been poorly investigated, though recent studies have defined and characterized the core promoter regions of hMSH2 and hMLH1. Therefore, to investigate the presence of germ-line mutations, we screened the core promoter regions of hMSH2 and hMLH1 from 157 nonmalignant control individuals, 40 cases of HNPCC, 56 suspected HNPCC cases, and 45 sporadic early onset colorectal cancer patients. Three novel germ line mutations of the hMSH2 promoter were identified in two suspected HNPCC cases and one sporadic early onset colorectal cancer patient but not in the 157 nonmalignant controls, namely, an A insertion at position -80, a G-to-A transition at position -190, and a G-to-C transversion at position -225. Tumors from patients containing the promoter mutations displayed microsatellite instability. The A insertion at -80 is within a sequence homologous to the consensus sequence for E1AF and very close to the major transcription start point. Luciferase assay demonstrated that the -80A insertion and the -190A allele decreased the transcriptional efficiency by 82 and 77%, respectively, and the 225C allele increased the transcriptional efficiency by 466%. The -80A insertion allele was detected only in affected members within the family and showed novel transcription factor binding ability. Furthermore, the loss of single nucleotide polymorphism allelic expression was identified in blood of the patient containing the -80A insertion. Our results indicate that mutations in the promoter region of hMSH2 have a limited role in development of suspected HNPCC and sporadic early onset colorectal cancer. PMID- 11782356 TI - Psoriasin expression in mammary epithelial cells in vitro and in vivo. AB - We determined, by serial analysis of gene expression (SAGE) analysis of normal and DCIS (ductal carcinoma in situ) mammary epithelial cells, that psoriasin and several other genes implicated in psoriasis are aberrantly expressed in high grade, comedo DCIS. Real-time PCR, mRNA in situ hybridization, and immunohistochemical analysis of breast carcinomas confirmed that psoriasin is frequently overexpressed in estrogen receptor-negative tumors. To gain insight into regulatory pathways that control psoriasin expression, we developed polyclonal and monoclonal antibodies and investigated mechanisms that may account for elevated levels of psoriasin in DCIS. Here, we report that loss of attachment to extracellular matrix, growth factor deprivation, and confluent conditions dramatically up-regulate psoriasin expression in MCF10A mammary epithelial cells. All of these conditions are characteristic of high-grade DCIS and psoriatic skin lesions; therefore, the same mechanisms may be responsible for increased expression of psoriasin in vitro and in vivo. PMID- 11782357 TI - Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. AB - CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that is involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Because CTCF targets include oncogenes and tumor suppressor genes, we screened over 100 human tumor samples for mutations that might disrupt CTCF activity. We did not observe any CTCF mutations leading to truncations/premature stops. Rather, in breast, prostate, and Wilms' tumors, we observed four different CTCF somatic missense mutations involving amino acids within the ZF domain. Each ZF mutation abrogated CTCF binding to a subset of target sites within the promoters/insulators of certain genes involved in regulating cell proliferation but did not alter binding to the regulatory sequences of other genes. These observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function." PMID- 11782358 TI - Low-level microsatellite instability occurs in most colorectal cancers and is a nonrandomly distributed quantitative trait. AB - About 10-15% of colorectal cancers show high-level microsatellite instability. The characteristics and very existence of low-level instability (MSI-L) are unclear, although some studies have found associations between MSI-L and molecular characteristics, notably more frequent K-ras mutations and a low level of allele loss near APC. We have attempted to define a MSI-L group of tumors by analyzing 107 sporadic colorectal carcinomas at 44 microsatellites. Ten (9.7%) MSI-H cancers were identified, but there was no evidence for a discrete MSI-L group. However, the 97 non-MSI-H cancers showed greater variation in the frequency of MSI than was expected by chance. Most cancers (68%) in the non-MSI-H group showed some MSI and could therefore be classed as nominally MSI-L. No association was found between MSI-L (or the level of MSI) and any clinicopathological or molecular variable, including K-ras mutation and loss of heterozygosity at APC. The causes of variation in level of the MSI in non-MSI-H colorectal cancers are unknown, but the differences are quantitative and probably reflect the evolutionary histories of the cancers rather than qualitatively different genetic pathways of tumorigenesis. PMID- 11782359 TI - Primary prostate stromal cells modulate the morphology and migration of primary prostate epithelial cells in type 1 collagen gels. AB - The effects of human primary prostatic stromal cells on the migration and morphogenesis of human prostatic epithelial cells, derived from tumor or benign prostatic hyperplasia tissue, were studied using a three-dimensional coculture system. Epithelial cells from tumor or benign tissue migrated efficiently into collagen gels populated with stromal cells from benign tissue. Only epithelial cells from benign prostate formed acinus-like structures that exhibited differentiated prostatic function and strong expression of membrane-associated E cadherin. In gels populated by stromal cells from tumor tissue, migration of primary prostatic epithelial cells did not occur. In the absence of stromal cells, primary epithelial cells were unable to proliferate. This three dimensional culture system allows closely controlled manipulation and analysis in vitro of interactions between prostatic epithelial and stromal cells. PMID- 11782360 TI - Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth. AB - Cyclooxygenase, involved in tumor growth and angiogenesis, converts arachidonic acid to prostaglandin (PG)H(2), which is immediately converted to bioactive prostanoids including PGE(2), PGD(2), thromboxane (TX)A(2) and PGI(2). To test the hypothesis that changes in the prostanoid profile alter cancer growth, we transduced the retroviral vectors carrying TXA(2) synthase cDNA or PGI(2) synthase cDNA to colon-26 adenocarcinoma cells and subsequently inoculated each transformant to syngeneic BALB/c mice. Tumors derived from TXA(2) synthase transformants grew faster (280%, day 8, versus null-vector control; P < 0.05) and showed more abundant vasculature (204%, versus null-vector control; P < 0.01), whereas tumors from PGI(2) synthase transformants presented opposite effects. These effects by the transgenes were reversed by administration of specific inhibitors. These results suggest that the profile of downstream metabolites of cyclooxygenase in cancer cells can be a determinant for tumor development. PMID- 11782361 TI - Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. AB - The essential requirement for polyamines for normal cell growth and differentiation may be partly attributed to their influence on gene expression, a process regulated by the acetylation state of nucleosomal histones. We used transgenic mice to examine the effects of constitutive expression of ornithine decarboxylase (ODC), a key rate-limiting enzyme in polyamine biosynthesis, on histone acetylation in epithelial cells in skin. As compared with the skin of normal littermate mice, both intrinsic histone acetyltransferase (HAT) and deacetylase activities are elevated in ODC transgenic skin. Skin tumors that form spontaneously in ODC/Ras double transgenic mice exhibit exceptionally high HAT activity having a distinct specificity for Lys-12 in the tail domain of histone H4, which may have implications for gene transcription. However, acetylation of histones by HAT enzymes was impeded in cultured ODC transgenic keratinocytes, and there were only modest changes in levels of acetylated histones in the skin of ODC transgenic mice. Treatment with the ODC enzyme inhibitor alpha difluoromethylornithine, which results in regression of ODC/Ras tumors, reverses the effects on HAT and deacetylase enzyme function, implicating polyamine biosynthesis in the regulation of histone acetylation. Polyamines do not directly stimulate the enzymatic activity of either p300 or p300/CREB-binding protein (CBP)-associated factor, members of two distinct classes of HAT enzymes, implying that the elevated CBP/p300-associated HAT activity detected in ODC transgenic skin is attributable to indirect influence of polyamines. These results suggest that multiple mechanisms exist by which endogenous polyamines influence chromatin in mammals. Furthermore, they suggest that the elevated polyamine levels inherent in many solid tumors alter chromatin structure, likely affecting gene expression and promoting the neoplastic process. PMID- 11782362 TI - Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts. AB - Stimulation of the Ras-mitogen-activated protein kinase (MAPK) pathway by growth factors, phorbol esters, and oncoproteins results in the phosphorylation of histone H3. Rsk-2 and MSK1 have been reported to be H3 kinases activated by the Ras-MAPK signal transduction pathway. In this study, we used inhibitors of Rsk-2 and MSK1 to decide which of these kinases was responsible for the 12-O tetradecanoylphorbol-13-acetate (TPA)-induced phosphorylation of H3 in 10T(1/2) and Ciras-3 (H-ras-transformed 10T(1/2)) mouse fibroblasts. These studies demonstrated that MSK1, but not Rsk-2, was the H3 kinase activated in these cells. Furthermore, assays with Rsk-2 showed that this kinase phosphorylates H2B but not H3 in vitro. H89, a potent MSK1 inhibitor, prevented TPA induction of H3 phosphorylation and diminished the TPA-induced expression of the c-fos and urokinase plasminogen activator genes. We propose that persistent activation of the Ras-MAPK pathway and MSK1 resulting in the elevation of phosphorylated H3 levels may contribute to the aberrant gene expression observed in the oncogene transformed cells. PMID- 11782363 TI - Effect of normal endometrial stroma on growth and differentiation in Ishikawa endometrial adenocarcinoma cells. AB - Endometrial cancer is characterized by alterations in the stromal cells and the supporting extracellular matrix in addition to the intrinsic alterations of the malignant epithelial cells. We have developed a cell culture model that demonstrates the role of stromal cells in the regulation of proliferation, hormone responsiveness, and differentiation of an endometrial adenocarcinoma cell line (Ishikawa). Conditioned medium (CM) was collected from normal primary human endometrial stromal cells grown on plastic or within the basement membrane extract, Matrigel. The CM produced by stromal cells cultured in contact with Matrigel markedly inhibited Ishikawa cell proliferation compared with CM from stromal cells cultured on plastic. Ishikawa cell proliferation varied with steroid hormone treatment in the presence of CM from stromal cells embedded in Matrigel. When the Ishikawa cells were placed in coculture in contact with stromal cells in Matrigel, production of a differentiated epithelial secretory product, glycodelin, was induced. Gene expression of stromal cell hormone receptors, growth factors, and integrins was analyzed by reverse transcription PCR in the presence of Matrigel to determine the potential factors involved in stromal regulatory function. These combined studies imply that the phenotype of the Ishikawa cells can be induced to differentiate to more closely resemble normal endometrial epithelium by reintroduction of stromal factors and appropriate extracellular matrix. Additionally, the study shows that basement membrane proteins influence the regulatory function of stromal cells as they mediate epithelial cell growth. PMID- 11782364 TI - Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. AB - Carcinogenesis involves a multistep process whereby a normal healthy cell undergoes both immortalization and oncogenesis to become fully transformed. Immortalization results from the subversion of critical cell cycle regulatory checkpoints, thereby allowing a cell to extend its finite life span and to maintain telomeric length. Oncogenesis is the manifestation of additional genetic events that are capable of conferring upon the cell an actual growth advantage. Such an advantage may relieve a cell of its normal requirements for a particular growth factor or may enhance the ability of a cell to proliferate outside of its normal microenvironment. To further investigate this multistep process, we developed an immortalized mammary epithelial cell line by overexpressing the catalytic subunit of telomerase (human telomerase reverse transcriptase) in primary human mammary epithelial cell lines. We present evidence that the overexpression of human telomerase reverse transcriptase was sufficient to extend the life span of the cells and allow for additional events that lead to immortalization. The result was the establishment of an IMEC line. Biochemical analysis of these cells indicates a basal epithelial phenotype with expression of high molecular weight cytokeratins. We show that continued growth of the IMECs is rigorously dependent upon both insulin and epidermal growth factor, and that the mitogenic effects of these factors on the IMECs are mediated in part by AKT. In addition, IMECs express the p53 family member DeltaN-p63-alpha, which is found in basal epithelial cells of many tissues and has been implicated as playing an essential role in normal epithelial development. Our studies suggest that the immortalization of basal epithelial cells of the mammary gland may be an early step in the initiation of a subset of breast cancers with a basal epithelial phenotype. PMID- 11782365 TI - Distinct spectrum of mutations induced by crocidolite asbestos: clue for 8 hydroxydeoxyguanosine-dependent mutagenesis in vivo. AB - DNA damage due to reactive oxygen or nitrogen species is proposed to be involved in the molecular mechanism of asbestos-induced carcinogenicity. However, indications for this hypothesis came mainly from in vitro assays using cultured cells or cell-free systems. In the present study, the mutagenicity of crocidolite fibers and the underlying molecular mechanisms were investigated in vivo. Mutation frequencies were determined in DNA of omenta, a relevant target tissue for mesothelioma carcinogenesis, using lacI transgenic rats. The mutagenic effect of 2 and 5 mg of crocidolite asbestos was demonstrated, with a maximal relative increase in mutation frequency of 3.4 compared with the control group. The molecular analysis of the mutations revealed striking differences according to mutation types between asbestos-induced mutations and spontaneous mutations. Therefore, a specific molecular mechanism induced by crocidolite that differs from that induced by the generation of spontaneous mutations can be proposed. G to T transversions, which are known to be induced by the premutagenic DNA adduct 8-hydroxydeoxyguanosine (8-OHdG), were the most prominent mutation type (29%) within crocidolite-induced mutations. In additional experiments, 8-OHdG in DNA of omenta from rats treated with 1 or 2 mg of crocidolite asbestos was determined. Levels of 8-OHdG in animals treated with crocidolite were significantly increased compared with negative controls. These data give strong evidence for the involvement of reactive oxygen or nitrogen species in crocidolite-induced mutagenesis in vivo. PMID- 11782366 TI - Comparative aflatoxin B(1) activation and cytotoxicity in human bronchial cells expressing cytochromes P450 1A2 and 3A4. AB - Some epidemiological evidence suggests a link between the inhalation of aflatoxin B(1) (AFB(1))-contaminated grain dusts and increased lung cancer risk. However, the mechanisms of AFB(1) activation and action in human lung are not well understood. We compared AFB(1) action in SV40 immortalized human bronchial epithelial cells (BEAS-2B) with two transfected cell lines that stably express human cytochromes P450 (CYPs) 1A2 (B-CMV1A2) and 3A4 (B3A4), the principal CYPs thought to activate this mycotoxin in human liver. All three cell types retained catalytically active glutathione S-transferase, the key phase II enzyme that detoxifies metabolically activated AFB(1). B-CMV1A2 and B3A4 cells expressed methoxyresorufin-O-demethylase (MROD) and nifedipine oxidase activities, respectively, and were 3000- and 70-fold more susceptible, respectively, to the cytotoxic effects of AFB(1) than the control cell line (BEAS-2B). When cultured with a range of low, environmentally relevant AFB(1) concentrations (0.02-1.5 microM), control cells formed barely detectable AFB(1)-DNA adducts, whereas B CMV1A2 cells formed significantly more adducts than B3A4 cells. In B-CMV1A2 cells, formation of AFB(1)-DNA adducts was inhibited by the CYP 1A2 inhibitor 7,8 benzoflavone, whereas formation of AFB(1)-DNA adducts in B3A4 cells was inhibited by the CYP 3A4 inhibitor 17alpha-ethynylestradiol. Competitive reverse transcription-PCR analysis showed that only the CYP-transfected cell lines expressed CYP mRNA. When adjusted for CYP mRNA expression, B-CMV1A2 cells were more efficient in the formation of cytotoxic and DNA-alkylating species at low AFB(1) concentrations, whereas B3A4 cells were more efficient at high concentrations. Our results affirm the hypothesis that, as in human liver microsomes, CYP 1A2 in human lung cells appears to have a more important role than CYP 3A4 in the bioactivation of low AFB(1) concentrations associated with many human exposures. Therefore, it is possible that under conditions in which appropriate CYPs are expressed in lung, inhalation of AFB(1) may result in increased risk of lung cancer in exposed persons. PMID- 11782368 TI - Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. AB - The factors controlling epithelial proliferation in ductal carcinoma in situ (DCIS) are unclear. Antiestrogens are effective in the prevention of the majority of estrogen receptor-positive, but not estrogen receptor (ER)-negative breast cancers, which suggests that other factor(s) are promoting proliferation in ER negative DCIS. Mutated or overexpressed tyrosine kinases are frequently associated with tumor development. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved with mitogenesis and is expressed in ER negative DCIS. We hypothesized that EGFR is central in driving proliferation in ER-negative/EGFR-positive DCIS. The purpose of this study was to establish whether the EGFR tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (Iressa), can reduce epithelial proliferation and increase apoptosis in EGFR-positive DCIS. Breast tissue from 16 women undergoing surgery for DCIS were implanted into 16-32 immunosuppressed mice/experiment (8 xenografts/mouse). Treatment commenced 2 weeks after implantation and consisted of once daily oral gavage with ZD1839 at doses ranging from 10 to 200 mg/kg for 14-28 days; appropriate controls were present. Xenografts were removed on days 14, 21, 28, and 42 after implantation and then assessed for proliferation (LI) by Ki67 immunostaining and apoptosis index (AI) by morphology. All Ps reported are two-sided. Overall, a 56% reduction in epithelial proliferation was seen with Iressa in EGFR-positive DCIS. EGFR-TK inhibition compared with vehicle controls resulted in a fall in Geometric Mean Labeling Index (LI) after 14 days (day 28) of treatment both in ER-negative/EGFR positive DCIS [6.5% interquartile range (IQR, 3.8-11.1) versus 13.9% (IQR, 12.0 16.3%); F(1,3) = 103; P = 0.002] and ER-positive/EGFR-positive DCIS [4.6% (IQR, 3.9-5.2%) versus 11.7% (IQR, 9.2-15.5); F(1,2) = 32.3; P = 0.03]. EGFR-TK inhibition had similar effects on the "at risk" normal breast epithelium adjacent to DCIS in the treated epithelium LI day 28 [ZD1839 2.2% (IQR, 1.7-3.3%) compared with control 3.8% (IQR, 2.4-5.4%); F(1,14) = 29.2; P = 0.00009] and in addition increased epithelial apoptotic index at day 21 [ZD1839 0.38 (0.23-0.83) compared with control 0.19 (0.1-0.25); F(1,6) = 12.2; P = 0.013]. The effect on epithelial proliferation was still significant after 28 days of treatment [for both DCIS (F1,29) = 24; P = 0.039 and normal breast F(1,6) = 47.3; P = 0.0005]. EGFR-TK inhibition with ZD1839 offers a novel approach to the treatment of EGFR-positive DCIS, regardless of ER status, and provides a potential new chemopreventative approach in patients at high risk of breast cancer. PMID- 11782367 TI - Activation of the aromatic hydrocarbon receptor pathway is not sufficient for transcriptional repression of BRCA-1: requirements for metabolism of benzo[a]pyrene to 7r,8t-dihydroxy-9t,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. AB - Reduction of BRCA-1 expression through nonmutational events may be a predisposing event in the onset of sporadic breast cancer. In this study, we investigated the mechanisms through which the environmental carcinogen benzo[a]pyrene (B[a]P) lowered BRCA-1 mRNA levels in breast cancer MCF-7 cells. We report that B[a]P does not compromise the stability of BRCA-1 mRNA, but represses transcriptional activity of a 1.69-kb BRCA-1 (pGL3-BRCA-1) promoter fragment that contains both exon-1A and exon-1B transcription start sites. The loss of BRCA-1 promoter activity was accompanied by accumulation of CYP1A1 and BAX-alpha mRNA and p53 and p21 protein, whereas levels of Bcl-2 mRNA were reduced. The aromatic hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is not metabolized, did not affect BRCA-1 promoter activity or the cellular levels of BRCA-1 and p53 protein, but it did induce a CYP1A1-like promoter. Conversely, treatment with the B[a]P metabolite 7r,8t-dihydroxy-9t,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE) repressed BRCA-1 promoter activity and protein, while increasing p53 and p21 protein levels. Transient expression of dominant negative p53 ((175)Arg-->His) counteracted the detrimental effects of BPDE on BRCA-1 promoter activity and protein levels. Similarly, treatment with B[a]P, TCDD, or BPDE failed to repress transcription from the pGL3-BRCA-1 construct transfected into ZR75.1 breast cancer cells containing mutated p53 ((152)Pro- >Leu). We conclude that activation of the aromatic hydrocarbon receptor is not sufficient for down-regulation of BRCA-1 transcription, which is, however, inhibited by the B[a]P metabolite BPDE through a p53-dependent pathway. PMID- 11782369 TI - Quantitation of metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone after cessation of smokeless tobacco use. AB - Two major metabolites of the tobacco-specific lung carcinogen 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were previously shown to be highly persistent in human urine after cessation of cigarette smoking. We hypothesized that NNK or its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanol (NNAL), was sequestered in the lung. In this study, we further evaluated this hypothesis by quantifying the NNK metabolites, NNAL and its glucuronides (NNAL-Gluc), in urine and plasma after cessation of smokeless tobacco use, in which NNK is administered p.o. rather than by inhalation. Thirteen male nonsmokers, 11 snuff dippers and 2 tobacco chewers, participated in the study. Urine and plasma were obtained at baseline and at intervals 2-126 days after cessation of smokeless tobacco use. The distribution half-lives t(1/2alpha) (days) of NNAL (1.32 +/- 0.85 versus 3.35 +/- 1.86) and NNAL-Gluc (1.53 +/- 1.22 versus 3.89 +/- 2.43) were significantly shorter in smokeless tobacco users than in smokers. There were no significant differences in the terminal half-lives t(1/2beta) (days) of NNAL (26.3 +/- 16.7 versus 45.2 +/- 26.9) and NNAL-Gluc (26.1 +/- 15.1 versus 39.6 +/- 26.0) in smokeless tobacco users and smokers. Baseline levels as well as renal clearance of the NNK metabolites correlated with number of tins or pouches of smokeless tobacco consumed. Ratios of (S)-NNAL:(R) NNAL and (S)-NNAL-Gluc:(R)-NNAL-Gluc in urine were significantly (3.1-5.7 times) higher 7 days after cessation than at baseline in both smokeless tobacco users and smokers, indicating stereoselective retention of (S)-NNAL. Collectively, the results of this study suggest that there is a receptor in the human body, possibly in the lung, for (S)-NNAL, the more carcinogenic NNAL enantiomer. These data may have considerable implications for understanding mechanisms of tumor induction by NNK. PMID- 11782370 TI - Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. AB - Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT SSX fusion type, pathology, and clinical course in a retrospective multi institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be the single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the associations of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences. PMID- 11782371 TI - p300 Modulates the BRCA1 inhibition of estrogen receptor activity. AB - We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER alpha) in human breast and prostate cancer cell lines but only weakly inhibits ER alpha activity in cervical cancer cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999). We now report that the ability of BRCA1 to repress ER-alpha activity correlates with its ability to induce down-regulation of the cellular levels of the transcriptional coactivator p300 in breast and prostate, but not in cervical cancer cells. On the other hand, BRCA1 failed to alter the expression of the CREB binding protein (CBP), the structural and functional homologue of p300, in any of these cell types. Ectopic expression of either p300 or CBP "rescued" (i.e., reversed) the BRCA1 inhibition of ER-alpha activity, whereas two other nuclear receptor coactivators, the p300/CBP-associated factor (PCAF) and the glucocorticoid receptor-interacting protein-1 (GRIP1), failed to rescue the ER alpha activity. The rescue function mapped to the cysteine-histidine rich domain CH3, a region of p300/CBP that we found to interact directly with the conserved COOH-terminal activation domain (AF-2) of ER-alpha. p300 and ER-alpha were also found to interact in vivo and to colocalize within the nucleus in breast cancer cells. These findings suggest that the cofactors p300 and CBP modulate the ability of the BRCA1 protein to inhibit ER-alpha signaling. They further suggest that the BRCA1 inhibition of ER-alpha activity may be attributable, at least in part, to the down-regulation of p300. PMID- 11782372 TI - The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. AB - XRCC1, a protein directly involved in the repair of DNA base damage, contains at least three common polymorphisms. One of these, the codon 399 arg-->gln variant, has been associated with several cancer-related biomarkers, suggesting it may have functional significance in exposure-induced cancers. However, results from case-control studies have yielded conflicting results. We investigated the XRCC1 arg399gln polymorphism and its interaction with carcinogen exposure in a large, population-based case-control study of non-melanoma skin cancer. Cases were derived from an incident survey of all newly diagnosed non-melanoma skin cancer in New Hampshire, and controls were population based and frequency matched to cases on age and sex (n = 1176). Exposure information was derived from a detailed interviewer-administered questionnaire, and XRCC1 genotype was determined from blood-derived DNA using a PCR-RFLP method. Overall, the XRCC1 homozygous variant gln399gln genotype was related to a significantly reduced risk of both basal cell [BCC; odds ratio (OR) 0.7, 95% confidence interval 0.4-1.0] and squamous cell carcinoma (SCC; OR 0.6, 95% confidence interval 0.3-0.9). There was no significant gene-environment interaction of the variant XRCC1 genotype and a history of therapeutic X-ray exposure. However, there was a statistically significant multiplicative interaction of XRCC1 genotype and lifetime number of sunburns in SCC [likelihood ratio test (2 d.f.), P < 0.02]. Although the absolute risk of SCC associated with sunburns was similar across genotypes, the relative risk of SCC associated with painful sunburn history was significantly higher for homozygous variants than wild types (OR 6.8 for gln399gln and 1.5 for arg399arg). In summary, our data show that the homozygous XRCC1 variant (gln399gln) is associated with a lower risk of non-melanoma skin cancer and suggest that the etiology of sunburn-related SCC may be significantly different by XRCC1 genotype. These data, using the classic skin carcinogenesis model, provide new insight on the role of the XRCC1 399 polymorphism in neoplasia and may help explain the conflicting results relating this polymorphism to cancer risk at various sites. PMID- 11782373 TI - Mechanisms of cell cycle arrest by methylseleninic acid. AB - Methylseleninic acid (MSA) is a monomethylated form of selenium effective in inhibiting cell growth in vitro and experimental mammary carcinogenesis in vivo. MSA offers particular advantage in cell culture experiments because it is stable in solution and provides a monomethylated form of selenium that can be reduced by cellular reducing systems and released nonenzymatically within a cell. In the present study, MSA was used to elucidate the mechanisms of cell growth inhibition by selenium. These studies were performed using a mouse mammary hyperplastic epithelial cell line, TM6. MSA induced a rapid arrest of synchronized cells in the G(1) phase of the cell cycle. This effect was accompanied by a reduction in total cellular levels of cyclin D1. Whereas MSA had no effect on total levels of the cyclin-dependent kinase (CDK)4, the amount of CDK4 immunoprecipitated with cyclin D1 in MSA-treated cells was decreased as was the kinase activity of the immunoprecipitated complex. MSA did not significantly affect cyclin E or associated regulatory molecules. Treatment with MSA suppressed the hyperphosphorylated form of retinoblastoma (Rb) with a commensurate increase in the hypophosphorylated form. Levels of E2F-1 bound to Rb also were elevated. Levels of insulin-like growth factor-I receptor and phosphorylated Akt were reduced by MSA. It is concluded that MSA induces a G(1) arrest in the cell cycle. This effect may be induced by MSA via its modulation of insulin-like growth factor-I-mediated signal transduction leading to inhibition of Akt activation and limitation of cyclin D1-CDK4-mediated phosphorylation of Rb. PMID- 11782374 TI - Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. AB - The inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) are overexpressed in colonic tumors of humans, as well as in colon tumors that develop in rats after the administration of the colon-specific carcinogen, azoxymethane (AOM). iNOS may regulate COX-2 production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to assess the potential chemopreventive properties of highly selective iNOS inhibitors, administered individually and in combination with a selective COX-2 inhibitor, on the development of AOM-induced colonic aberrant crypt foci (ACF). F344 rats were fed experimental diets containing one of the following: 0, 10, 30, or 100 parts/million (ppm) of the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine tetrazole-amide (SC-51); 1800 ppm of the less potent, selective iNOS inhibitor aminoguanidine (AG); 500 ppm of the COX-2 inhibitor celecoxib; 320 ppm of the nonsteroidal anti-inflammatory sulindac (positive control); or 30 ppm of SC-51 with 500 ppm of celecoxib, and 100 ppm of SC-51 with 500 ppm of celecoxib. One and 2 weeks later, rats received s.c. injections of AOM at a dose of 15 mg/kg of body weight. At 17 weeks of age, all rats were sacrificed. Colons were evaluated for ACF, and colonic mucosae were assayed for COX and NOS isoform enzyme activities. Samples of venous blood, collected at various time points, were analyzed for these agents. SC-51, administered alone, demonstrated dose-dependent inhibition of the incidence of colonic ACF. The highest doses of SC-51 (100 ppm) and AG (1800 ppm) significantly suppressed the incidence of colonic ACF (P < 0.01 and < 0.001, respectively) and crypt multiplicity in terms of numbers of aberrant crypts/focus (P < 0.0001). Importantly, the combination of either low or high effective doses of SC-51 (30 or 100 ppm) and celecoxib (500 ppm) suppressed AOM-induced colonic ACF formation (P < 0.05 and < 0.001, respectively) and reduced multiplicity of four or more aberrant crypts/focus (P < 0.0001) to a greater extent than did these agents administered individually. As expected, sulindac inhibited colonic ACF formation (P < 0.001) and reduced the multiplicity of four or more aberrant crypts (P < 0.0001) to approximately 45%. The enzymatic activities of COX-2 and iNOS were significantly induced in the AOM-treated animals, and administration of the iNOS inhibitors, SC-51 and AG, significantly inhibited the activities of both iNOS and COX-2 in the colonic mucosa. The combined administration of SC-51 and celecoxib inhibited the COX-2 activity to a greater extent than did either of these agents administered alone. These findings support the hypothesis that selective iNOS inhibitors may have chemopreventive properties and that coadministration with a selective COX-2 inhibitor may have additional chemopreventive potential. PMID- 11782375 TI - Tumor-targeted gene therapy for nasopharyngeal carcinoma. AB - The unique feature of human nasopharyngeal carcinoma (NPC) is its almost universal association with the EBV, which is expressed in a latent form exclusively in cancer cells, and not in the surrounding tissues. We have exploited this differential by constructing a novel replication-deficient adenovirus vector (ad5.oriP) in which transgene expression is under the transcriptional regulation of the family of repeats domain of the origin of replication (oriP) of EBV. When EBNA1, one of the latent gene products of EBV, binds to the family of repeats sequence, this activates transcription of downstream genes. Vector constructs were made using the beta-galactosidase and luciferase reporter genes (ad5oriP.betagal and ad5oriP.luc) or the p53 tumor suppressor gene (ad5oriP.p53). 5-Bromo-4-chloro-3-indolyl-beta-D galactopyranoside staining demonstrated extensive expression only in EBV-positive NPC cells, specifically in response to the presence of EBNA1. The relative difference in expression between EBV-positive and -negative cell lines is approximately 1000-fold. This selective expression was corroborated in EBV positive and -negative tumor models, along with an absence of transgene expression in the host liver. Significant cytotoxicity was achieved using the adv.oriP.p53 therapeutic gene only in EBV-positive NPC cells, which was enhanced with the addition of ionizing radiation. Cytotoxicity was mediated primarily by induction of apoptosis. These results demonstrate that the oriP sequence can achieve high levels of gene expression targeted specifically to EBV-positive NPC cells in the context of the adv vector. This has now provided the tumor-specific expression system from which additional interventions can be evaluated in future treatment strategies for patients with nasopharyngeal cancers. PMID- 11782376 TI - Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11) induced diarrhea. AB - The therapeutic efficacy of irinotecan (CPT-11), a DNA topoisomerase inhibitor, is often limited by the induction of severe late-onset diarrhea. This prodrug and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), have a labile alpha-hydroxy-lactone ring that undergoes pH-dependent reversible hydrolysis. At physiological pH and higher, equilibrium favors the less toxic carboxylate form, whereas at acidic pH, the more potent lactone form is favored. We have reported previously that the initial uptake rate of CPT-11 and SN-38 by intestinal cells was significantly different between the respective lactone and carboxylate form. Results from the present study in HT-29 cells further demonstrate the correlation between the CPT-11/SN-38 initial uptake rate and the induced toxicity, cell cycle alteration, apoptosis, and colony-forming efficiency. The exposure of HT-29 cells to SN-38 for a limited period of time (<2 h) was sufficient to induce these events. Because the decreased initial uptake of SN-38 carboxylate resulted in a reduced cellular toxicity, we postulated that the CPT-11-induced diarrhea was preventable by influencing the equilibrium toward the carboxylate form and, thus, reducing its intestinal uptake. In the golden Syrian hamster model, p.o. sodium bicarbonate supplementation (5 mg/ml in drinking water) led to alkalization of the intestinal contents. In addition, this alkalization resulted in the reduction of the histopathological damage to the mucosa of the small and large intestine, as well as a 20% reduction of the intestinal SN-38 lactone concentration of animals receiving CPT-11 (20-50 mg/kg x 7 days). Taken together, these results from in vitro and in vivo studies support intestinal alkalization by sodium bicarbonate supplementation as a preventive mechanism against CPT-11-induced diarrhea. In addition, this provides a strong rationale for the usage of this measure as an adjunct to CPT-11 treatment. PMID- 11782377 TI - Pharmacologic mitogen-activated protein/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase inhibitors interact synergistically with STI571 to induce apoptosis in Bcr/Abl-expressing human leukemia cells. AB - Interactions between the kinase inhibitor STI571 and pharmacological antagonists of the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) cascade have been examined in human myeloid leukemia cells (K562 and LAMA 84) that express the Bcr-Abl kinase. Exposure of K562 cells to concentrations of STI571 that minimally induced apoptosis (e.g., approximately 200 nM) resulted in early suppression (i.e., at 6 h) of p42/44 MAPK phosphorylation followed at later intervals (i.e., > or =24 h) by a marked increase in p42/44 MAPK phosphorylation/activation. Coadministration of a nontoxic concentration of the MEK1/2 inhibitor PD184352 (5 microM) prevented STI571-mediated activation of p42/44 MAPK. Cells exposed to STI571 in combination with PD184352 for 48 h demonstrated a very dramatic increase in mitochondrial dysfunction (e.g., loss of DeltaPsim and cytosolic cytochrome c release) associated with procaspase-3 activation, poly(ADP-ribose) polymerase cleavage, and the appearance of the characteristic morphological features of apoptosis. Similar results were obtained using other pharmacological MEK1/2 inhibitors (e.g., PD 98059 and U0126) as well as another leukemic cell line that expresses Bcr-Abl (e.g., LAMA 84). However, synergistic induction of apoptosis by STI571 and PD184352 was not observed in human myeloid leukemia cells that do not express the Bcr-Abl kinase (e.g., HL-60 and U937) nor in normal human peripheral blood mononuclear cells. Synergistic potentiation of STI571-mediated lethality by PD184352 was associated with multiple perturbations in signaling and apoptotic regulatory pathways, including caspase-dependent down-regulation of Bcr-Abl and Bcl-2; caspase-independent down-regulation of Bcl-x(L) and Mcl-1; activation of JNK, p38 MAPK, and p34(cdc2); and diminished phosphorylation of Stat5 and CREB. Significantly, coexposure to PD184352 strikingly increased the lethality of a pharmacologically achievable concentration of STI571 (i.e., 1-2 microM) in resistant K562 cells expressing marked increases in Bcr-Abl protein levels. Together, these findings raise the possibility that treatment of Bcr-Abl expressing cells with STI571 elicits a cytoprotective MAPK activation response and that interruption of the latter pathway (e.g., by pharmacological MEK1/2 inhibitors) is associated with a highly synergistic induction of mitochondrial damage and apoptosis. They also indicate that in the case of Bcr-Abl-positive cells, simultaneous interruption of two signal transduction pathways may represent an effective antileukemic strategy. PMID- 11782379 TI - Down-regulation of antihost alloreactivity after bone marrow transplant permits relapse of hematological malignancy. AB - Relapse of leukemia remains a common event after allogeneic bone marrow transplantation, despite potential donor antihost alloreactivity present in most transplants. This work examined posttransplant relapse of the DBA/2 P815 mastocytoma in a murine model of MHC-matched, minor histocompatibility antigen (mHAg)-mismatched bone marrow transplantation (BALB/c donors into DBA/2 recipients). Antihost alloreactivity was associated with reduction of posttransplant tumor burden and prolongation of survival, but posttransplant relapse commonly occurred. No evidence of acquired resistance to immune control was found in 12 relapse reisolates. Relapse tumors remained sensitive to donor antihost CTLs in vitro, suggesting continued expression of mHAgs. Reisolates also continued to express Fas. However, loss of posttransplant alloreactivity was observed at 3 weeks. This was temporally associated with the time of relapse. Antihost alloreactivity could be reactivated in stable graft-versus-host disease free recipients by immunization with host cells. The results of this study suggest that one mechanism for relapse after bone marrow transplant is acquired tolerance of allogeneic minor histocompatibility antigens and that posttransplant immunotherapy directed against mHAgs may induce antitumor activity. PMID- 11782378 TI - Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. AB - Overexpression of the epidermal growth factor receptor (EGFR) has been shown previously to correlate with enhanced malignant potential of many human tumor types, including glioblastoma multiforme (GBM). Anti-EGFR targeting has been demonstrated to enhance apoptosis and reduce both cellular invasion and angiogenic potential. It remains unclear whether absolute EGFR expression levels are sufficient to predict which tumors will respond best to anti-EGFR therapy. We have identified two primary GBM cell lines with equivalent EGFR expression levels with very different sensitivities to the EGFR receptor tyrosine kinase inhibitor, AG1478. This was apparent despite similar reductions in EGFR signaling in both cell lines, as measured by phospho-EGFR levels. AG1478 enhanced both spontaneous and radiation-induced apoptosis and reduced invasive potential in the GBM(S), but not in the GBM(R), cell line. The resistant GBM(R) cell line demonstrated an up regulation of insulin-like growth factor receptor I (IGFR-I) levels on AG1478 administration. This resulted in sustained signaling through the phosphoinositide 3-kinase pathway, resulting in potent antiapoptotic and proinvasion effects. Cotargeting IGFR-I with EGFR greatly enhanced both spontaneous and radiation induced apoptosis of the GBM(R) cells and reduced their invasive potential. Akt1 and p70(s6k) appeared to be important downstream targets of IGFR-I-mediated resistance to anti-EGFR targeting. These findings suggest that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy. PMID- 11782380 TI - NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells. AB - The NY-ESO-1 gene product is expressed by a range of human tumors and is recognized by antibodies from sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and MHC class II restricted tumor epitopes recognized by T lymphocytes. In particular, we previously reported that the NY-ESO-1 119-143 peptide contains at least two HLA DRB1*0401-presented epitopes that are recognized by melanoma-reactive CD4+ T cells. Here we report that the NY-ESO-1 119-143 peptide can be presented in the context of multiple HLA-DR alleles to stimulate tumor-reactive CD4+ T cells. The NY-ESO-1 119-143 peptide is able to bind to several DR molecules. The NY-ESO-1 119-143 peptide is also capable of inducing specific CD4+ T cells in vitro from peripheral blood lymphocytes of normal donors and patients with melanoma who express these HLA-DR alleles. These CD4+ T cells recognize NY-ESO-1(+), HLA matched or autologous melanoma cell lines, as well as autologous antigen presenting cells fed with the NY-ESO-1 protein. We also demonstrate that the NY ESO-1 119-143 peptide stimulates in vitro both Th1-type and Th2-type CD4+ T-cell responses from peripheral blood lymphocytes of normal donors and melanoma patients. Taken together, these data suggest a key role of the NY-ESO-1 119-143 peptide sequence in the induction of cellular and humoral responses against NY ESO-1-expressing tumors. They support the relevance of cancer vaccine trials with the NY-ESO-1 119-143 peptide in the large number of cancer patients with NY-ESO-1 expressing tumors. PMID- 11782381 TI - Elevated levels of Rad51 recombination protein in tumor cells. AB - Rad51 is the key enzyme for homologous recombination, an evolutionarily conserved mechanism for the repair of DNA damage and the generation of genetic diversity. Given the observation that many tumors become resistant to radiation therapy and DNA-damaging chemotherapeutics and also that tumor cell populations can acquire a high number of genetic alterations and then expand clonally, dysfunction of the mammalian Rad51 recombinase could play a major role in the multistep process of tumorigenesis. The data we present provide further strong support for this hypothesis. Using anti-Rad51 immunofluorescence staining, widely different tumor cell lines displayed increased numbers of nuclei with focally concentrated Rad51 protein compared with nonmalignant control cell lines. These nuclear foci are thought to represent a repairosome-type assembly of Rad51 and other proteins required for recombinational DNA repair. By Western blot analyses, the net amount of Rad51 protein was increased 2-7-fold in all tested tumor cell lines. Inhibition of de novo protein synthesis by cycloheximide treatment showed a similar half-life of Rad51 protein in normal and tumor cells. Fluorescence in situ hybridization experiments did not detect Rad51 gene amplifications in tumors. Because Northern blot analysis demonstrated highly elevated Rad51 mRNA levels, we conclude that the increases in Rad51 protein and nuclear foci formation in tumor cells are the result of transcriptional up-regulation. PMID- 11782382 TI - Osteonectin/SPARC induction by ectopic beta(3) integrin in human radial growth phase primary melanoma cells. AB - Expression of the beta(3) integrin subunit in melanoma in situ has been found to correlate with tumor thickness, the ability to invade and metastasize, and poor prognosis. Transition from the radial growth phase (RGP) to the vertical growth phase (VGP) is a critical step in melanoma progression and survival and is distinguished by the expression of beta(3) integrin. The molecular pathways that operate in melanoma cells associated with invasion and metastasis were examined by ectopic induction of the beta(3) integrin subunit in RGP SBcl2 and WM1552C melanoma cells, which converts these cells to a VGP phenotype. We used cDNA representational difference analysis subtractive hybridization between beta(3) positive and -negative melanoma cells to assess gene expression profile changes accompanying RGP to VGP transition. Fourteen fragments from known genes including osteonectin (also known as SPARC and BM-40) were identified after three rounds of representational difference analysis. Induction of osteonectin was confirmed by Northern and Western blot analysis and immunohistochemistry and correlated in organotypic cultures with the beta(3)-induced progression from RGP to VGP melanoma. Expression of osteonectin was also associated with reduced adhesion to vitronectin, but not to fibronectin. Osteonectin expression was not blocked when melanoma cells were cultured with anti-alpha(v)beta(3) LM609 mAb, mitogen activated protein kinase, or protein kinase C inhibitors, indicating that other signaling pathway(s) operate through alpha(v)beta(3) integrin during conversion from RGP to VGP. PMID- 11782383 TI - Global gene expression analysis of gastric cancer by oligonucleotide microarrays. AB - To gain molecular understanding of carcinogenesis, progression, and diversity of gastric cancer, 22 primary human advanced gastric cancer tissues and 8 noncancerous gastric tissues were analyzed by high-density oligonucleotide microarray in this study. Based on expression analysis of approximately 6800 genes, a two-way clustering algorithm successfully distinguished cancer tissues from noncancerous tissues. Subsequently, genes that were differentially expressed in cancer and noncancerous tissues were identified; 162 and 129 genes were highly expressed (P < 0.05) >2.5-fold in cancer tissues and noncancerous tissues, respectively. In cancer tissues, genes related to cell cycle, growth factor, cell motility, cell adhesion, and matrix remodeling were highly expressed. In noncancerous tissues, genes related to gastrointestinal-specific function and immune response were highly expressed. Furthermore, we identified several genes associated with lymph node metastasis including Oct-2 or histological types including Liver-Intestine Cadherin. These results provide not only a new molecular basis for understanding biological properties of gastric cancer, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric cancer. PMID- 11782384 TI - Abolishment of the Tyr-15 inhibitory phosphorylation site on cdc2 reduces the radiation-induced G(2) delay, revealing a potential checkpoint in early mitosis. AB - cdc2 is inactivated before mitosis by phosphorylation at its inhibitory sites, Thr-14 and Tyr-15. Irradiation prevents HeLa cells from completing the G(2)-M transition, and they arrest in G(2). Whereas phosphorylation at both of these sites occurs during the G(2) arrest, the individual role of each site in the G(2) delay has not previously been investigated. We have shown that the radiation induced G(2) delay is preserved in wild-type or cdc2-AY-transfected cells (which retain Tyr-15); this delay is abolished in cdc2-TF- or cdc2-AF-transfected cells (which lack Tyr-15). Thus Tyr-15, but not Thr-14, appears to be essential for development of a G(2) delay after radiation. Abolishment of the G(2) delay by mutation at Tyr-15 resulted in the accumulation of cells with condensed chromatin and disrupted lamin B, suggesting that these cells may be blocked at a second G(2)-M checkpoint in early mitosis (i.e., prophase). These data suggest (a) that the two inhibitory phosphorylation sites have distinct functions and that Tyr-15 phosphorylation, in particular, has a key role in the radiation-induced G(2) delay, and (b) that a second G(2)-M checkpoint exists in early mitosis and that activation of this checkpoint by radiation prevents cells that enter mitosis from progressing further. PMID- 11782385 TI - Heterogeneous expression of MAGE-A genes in occult disseminated tumor cells: a novel multimarker reverse transcription-polymerase chain reaction for diagnosis of micrometastatic disease. AB - Systemically disseminated tumor cells have become the subject of intensive research as the presumed seminal precursors of later distant metastasis. We describe here a novel sensitive multimarker nested reverse transcription (RT)-PCR capable of detecting the individual expression of human MAGE-A genes MAGE-1, -2, 3/6, -4, and -12 by rare, disseminated tumor cells in bone marrow and blood of patients with many different types of cancer. We analyzed bone marrow aspirates from 106 patients with breast, lung, colorectal, and prostate cancer and with different sarcomas. Heterogeneous expression of the different MAGE genes was found frequently in all those kinds of malignancies, in sharp contrast to 30 bone marrow and 20 blood samples from healthy donors, which were completely MAGE negative. Expression of at least one MAGE gene in bone marrow was more frequent than cytokeratin-positive tumor cells detected by immunocytochemistry, although the results of both tests overlapped considerably. In 30 patients with clinically localized prostate cancer, analysis by the multimarker MAGE RT-PCR of bilateral bone marrow aspirates from the right and left iliac crest revealed a positivity rate of 60%, which was twice as high as that obtained with either an established prostate-specific antigen RT-PCR or by cytokeratin-based immunocytochemistry. Analysis of primary prostate cancer revealed MAGE expression patterns considerably concordant with those found in the corresponding bone marrow aspirates. Prostate cancer patients carrying an exceptionally high risk of metastatic relapse, as defined by clinical prognostic factors, were significantly more often MAGE positive than patients with a distinctly lower risk (P = 0.02, Fisher's exact test). More frequent MAGE expression in the peripheral blood of patients with metastatic prostate cancer compared with those with clinically localized disease added further evidence for the prognostic impact of the multimarker MAGE RT-PCR. Moreover, MAGE-positive bone marrow samples from a small group of seven sarcoma patients demonstrated the relevance of our multimarker RT PCR in nonepithelial tumors. Because MAGE antigens can induce autologous cytolytic T lymphocytes in vivo, the determination of individual MAGE expression patterns in cancer patients may furthermore identify candidate vaccine targets for adjuvant immunotherapy. PMID- 11782386 TI - Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. AB - To identify novel tumor suppressor genes involved in ovarian carcinogenesis, we generated four down-regulated suppression subtraction cDNA libraries from two early-stage (stage I/II) and two late-stage (stage III) primary ovarian tumors, each subtracted against cDNAs derived from normal ovarian epithelial cell brushings. Approximately 600-700 distinct clones were sequenced from each library. Comparison of down-regulated clones obtained from early- and late-stage tumors revealed genes that were unique to each library which suggested tumor specific differences. We found 45 down-regulated genes that were common in all four libraries. We also identified several genes, the role of which in tumor development has yet to be elucidated, in addition to several under expressed genes, the potential role of which in carcinogenesis has been described previously (Bagnoli et al., Oncogene, 19: 4754-4763, 2000; Yu et al., Proc. Natl. Acad. Sci. USA, 96: 214-219, 1999; Mok et al., Oncogene, 12: 1895-1901, 1996). The differential expression of a subset of these genes was confirmed by semiquantitative reverse transcription-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control in a panel of 15 stage I and 15 stage III tumors of mixed histological subtypes. Chromosomal sorting of library sequences revealed that several of the genes mapped to known regions of deletion in ovarian cancer. Loss of heterozygosity (LOH) analysis revealed multiple genomic regions with a high frequency of loss in both early- and late-stage tumors. To determine whether loss of expression of some of the genes corresponds to loss of an allele by LOH, we used a microsatellite marker for one of the novel genes on 8q and have shown that loss of expression of this novel gene correlates with loss of an allele by LOH. In conclusion, our analysis has identified down-regulated genes, which map to known as well as novel regions of deletions and may represent potential candidate tumor suppressor genes involved in ovarian cancer. PMID- 11782387 TI - Identification of frequent G(2) checkpoint impairment and a homozygous deletion of 14-3-3epsilon at 17p13.3 in small cell lung cancers. AB - Accumulating evidence suggests that a coordinately controlled G(2) checkpoint prevents cells with damaged DNA from entering mitosis, thus playing an important role in the maintenance of chromosomal integrity. In the study presented here, we identified a homozygous deletion of the 14-3-3epsilon gene, which resides within a previously identified, commonly deleted region at 17p13.3 in lung cancers, in two small cell lung cancer cell lines that originate from distinct metastatic sites of the same patients. The introduction of 14-3-3epsilon induced significantly restored G(2) checkpoint responses, which resulted in the reduction of mitotic cells as well as of aberrant mitotic figures in the X-ray-irradiated 14-3-3epsilon-null small cell lung cancer cell line. Interestingly, we also found that the G(2) checkpoint response is frequently impaired to various degrees in a large fraction of small cell lung cancer cell lines. These findings suggest the possible involvement of the perturbed G(2) checkpoint in the pathogenesis of this aggressive form of human lung cancers. PMID- 11782388 TI - Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor dependent transcription in esophageal cancer cells. AB - beta-Catenin plays an important role in signal transduction pathways that regulate cellular differentiation and proliferation. The increased concentration of this protein in the cytoplasm favors its binding to the T-cell factor (TCF) family of DNA-binding proteins, and it subsequently translocates to the nucleus, where it induces transcription of specific genes. We explored mechanisms that lead to activation of beta-catenin/TCF-dependent transcription in esophageal squamous cell carcinoma (ESCC) independent of adenomatous polyposis coli and beta catenin mutation. Electrophoresis mobility shift assay demonstrated that TCF4 and beta-catenin form a complex and have DNA binding activity. However, there was no constitutive activation of beta-catenin/TCF-dependent transcription. Coculture experiments demonstrated that Wnt-1, but not Wnt-5A and Wnt-7A, activated the TCF reporter gene. Additionally, when cultured with Wnt-1-conditioned media, ESCC cell lines showed an accumulation of beta-catenin in the cytoplasm. Although both Wnt and epidermal growth factor inactivate glycogen synthase kinase 3beta, activation of epidermal growth factor receptor did not stabilize beta-catenin. A comparison of extracellular stimuli suggests that specific Wnt family members stabilize beta-catenin with resulting activation of TCF-dependent transcription in ESCC. PMID- 11782389 TI - Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts. AB - The bone and bone marrow are the most common sites of metastasis in breast cancer. Matrix metalloproteinases (MMPs), particularly MMP-2, produced by cancer cells or, more typically, induced in the adjacent normal stroma are necessary for the degradation of extracellular matrix essential for cancer metastasis. Here we describe a mechanism by which breast cancer cells can rapidly use MMP-2 produced by bone marrow fibroblasts (BMFs). MMP-2 is stored in an inactive conformation in association with the cell surface or extracellular matrix of BMFs. Cocultures of BMFs and the human breast cancer cell line MDA-MB-231 induce release of MMP-2 into the culture supernatant without up-regulation of MMP-2 synthesis in either cell. MMP-2 is present on the surface of BMFs and is displaced by MDA-MB-231 cells or by fibronectin or fragments of fibronectin containing the fibronectin type II modules. Moreover, when fibronectin is eluted from the surface of MDA-MB 231 cells, they lose the ability to induce the release of MMP-2 from BMFs. These data are consistent with the displacement of inactive MMP-2 bound to normal fibroblasts via its collagen-binding domain by fibronectin type II modules of cancer cell-associated fibronectin. Cancer cells can then use the proteinase to facilitate tissue invasion. Because an identical mechanism can be demonstrated using fibroblasts from different sources, it is likely to be important for the rapid movement of malignant cells into a variety of normal tissues. PMID- 11782390 TI - TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells. AB - Initial studies have identified TSP50 as a human testes-specific gene that is demethylated in breast cancer. In this study, we will present new data related to the TSP50 gene. We have found that the TSP50 gene product shares a similar enzymatic structure with many serine proteases. However, the most critical catalytic site, serine, has been replaced by threonine. Western analysis revealed that in human testes, the TSP50 antibody detected two closely positioned protein bands whose estimated molecular masses were 37 kDa, whereas in a large portion of breast cancer tissues, but not normal control tissues, only one band was present. Immunohistochemistry assays found TSP50 proteins located in the spermatocytes of human testes, whereas in situ hybridization and immunohistochemistry confirmed that gene activation in breast tumors took place in malignant mammary epithelial cells. These results suggested that the normal function of the TSP50 gene was involved in spermatogenesis, whereas the up-regulation of TSP50 in many breast cancer patients not only indicated that it might be a novel biomarker for this disease but also encouraged us to further explore the possibility of whether it was an oncogene. PMID- 11782391 TI - Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. AB - Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. Currently, no methods are available for measuring hK11 in biological fluids and tissues. Our aim was to develop immunological reagents and assays for measuring hK11 and examine if the concentration of this kallikrein is altered in disease states. We produced recombinant hK11 protein in a baculovirus system and used it to develop monoclonal and polyclonal antibodies against hK11. We then developed an immunofluorometric procedure for measuring hK11 in biological fluids and tissue extracts with high sensitivity and specificity. We further quantified hK11 in various biological fluids and in serum of patients with various cancers. The hK11 immunofluorometric assay is highly sensitive (detection limit, 0.1 microg/l) and specific (no detectable cross-reactivity for other homologous kallikreins). We established the tissue expression pattern of hK11 at the protein level and found the highest levels in the prostate, followed by stomach, trachea, skin, and colon. We have immunohistochemically localized hK11 in epithelial cells of various organs. We further detected hK11 in amniotic fluid, milk of lactating women, cerebrospinal fluid, follicular fluid, and breast cancer cytosols. However, highest levels were seen in prostatic tissue extracts and seminal plasma. hK11 in seminal plasma and prostatic extracts is present at approximately 300-fold lower levels than prostate-specific antigen and at approximately the same levels as hK2. hK11 expression in breast cancer cell lines is up-regulated by estradiol. Elevated serum levels of hK11 were found in 70% of women with ovarian cancer and in 60% of men with prostate cancer. This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma. PMID- 11782392 TI - Id2 is critical for cellular proliferation and is the oncogenic effector of N-myc in human neuroblastoma. AB - Perturbation of the function of the retinoblastoma (Rb) protein is found in most human tumors. Id2 is a natural target of the Rb protein that is recruited by Myc oncoproteins to bypass the tumor suppressor function of Rb. Here we report that an "N-Myc-Id2 pathway" persists during late development of the nervous system and parallels the rising levels of active Rb in neuronal precursors withdrawing from the cell cycle. An immunohistochemical analysis of primary neuroblastoma from 47 patients shows that expression of Id2 is strongly predictive of poor outcome, irrespective of other clinical and biological variables. Overexpression of Id2 mediates cellular transformation and is required to maintain the malignant behavior of neuroblastoma cells. Correspondingly, embryonic fibroblasts from Id2 null mice display impaired ability to proliferate. We suggest that Id2 overexpression may be a better prognostic indicator than N-myc gene amplification in neuroblastoma. Thus, disrupting Id2 function may lead to new and useful therapeutic strategies for cancer patients. PMID- 11782393 TI - Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels. AB - Therapeutic regimens such as radiation or chemotherapy attempt to exploit the physiological differences between normal and malignant tissue. Tissue redox status and pO(2) are two factors that are hypothesized to be different in normal and malignant tissues. Methods that can detect subtle differences in the above physiological parameters would greatly aid in devising appropriate treatment strategies. We have previously used in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques and shown that tumor tissues are highly reducing and hypoxic compared with normal tissues (P. Kuppusamy et al., Cancer Res., 58: 1562-1568, 1998). The purpose of the present study was to obtain spatially resolved redox data from normal and tumor tissues of radiation-induced fibrosarcoma (RIF-1) tumor-bearing mice and to examine the role of intracellular glutathione (GSH) on the tissue redox status. Experiments were performed using low-frequency (1.3 GHz) in vivo EPR spectroscopy and imaging techniques with a nitroxide redox probe. L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH synthesis, was used to deplete tissue GSH levels. The results show the existence of significant heterogeneity of redox status in the tumor tissue compared with normal tissue. The tumor tissues show at least 4-fold higher concentrations of GSH levels compared with normal tissues in the tumor-bearing mice. Also BSO treatment showed a differential depletion of GSH and reducing equivalents in the tumor tissue. Thus, it appears that there is significant heterogeneity of tumor redox status and that manipulation of the tumor redox status may be important in tumor growth and therapy. PMID- 11782394 TI - Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines. AB - We have reported previously that sigma-2 receptors are expressed in high densities in a variety of tumor cell types (B. J. Vilner et al., Cancer Res., 55: 408-413, 1995) and that various sigma ligands have cytotoxic effects (B. J. Vilner et al., J. Neurosci., 15: 117-134, 1995). Other investigators have demonstrated increased expression of sigma-2 receptors in rapidly proliferating tumors (R. H. Mach et al., Cancer Res., 57: 156-161, 1997) and the ability of some sigma ligands to inhibit proliferation (P. J. Brent and G. T. Pang, Eur. J. Pharmacol., 278: 151-160, 1995). We demonstrate here the ability of sigma-2 receptor agonists to induce cell death by a mechanism consistent with apoptosis. In breast tumor cell lines that are sensitive (MCF-7) and resistant (MCF-7/Adr-, T47D, and SKBr3) to antineoplastic agents, incubation with the sigma-2 subtype selective agonists CB-64D and CB-184 produced dose-dependent cytotoxicity (measured by lactate dehydrogenase release into medium). The EC(50) for this response was similar across cell lines, irrespective of p53 genotype and drug resistance phenotype. CB-64D and the subtype nonselective sigma-2 agonists haloperidol and reduced haloperidol induced terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining in MCF-7 and T47D cells, indicating that cell death occurs via apoptosis. Apoptosis was also indicated by increases in Annexin V binding caused by CB-64D. In MCF-7 cells, cytotoxicity and Annexin V binding induced by the antineoplastics doxorubicin and actinomycin D was partially or completely abrogated by certain specific and general inhibitors of caspases. In contrast, caspase inhibitors had no effect on sigma-2 receptor mediated (CB-64D and CB-184) cytotoxicity or Annexin V binding. Marked potentiation of cytotoxicity was observed when a subtoxic dose of CB-184 was combined with doxorubicin or actinomycin D, both in drug-sensitive (MCF-7) and drug-resistant (MCF-7/Adr-) cell lines. Haloperidol potentiated doxorubicin only in drug-resistant cells. These findings suggest the involvement of a novel p53- and caspase-independent apoptotic pathway used by sigma-2 receptors, which is distinct from mechanisms used by some DNA-damaging, antineoplastic agents and other apoptotic stimuli. These observations further suggest that sigma-2 receptors may be targets that can be therapeutically exploited in the treatment of both drug-sensitive and drug-resistant metastatic tumors. PMID- 11782395 TI - The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. AB - A workshop on childhood atypical teratoid/rhabdoid tumors of the central nervous system, sponsored by the National Cancer Institute and the Pediatric Brain Tumor Foundation of the United States, was held on January 29, 2001 in Bethesda, Maryland. Drs. Malcolm Smith, Jaclyn Biegel, and Roger Packer hosted the meeting. There were 22 participants from 14 institutions. The sessions were designed to review what was known about the biology and clinical behavior of rhabdoid tumors and to begin to develop treatment strategies that might be effective against this clinically aggressive group of malignancies. This report summarizes the biology sessions from the meeting. A detailed summary of the discussions regarding diagnostic studies and the roles for radiation therapy, chemotherapy, and bone marrow or stem cell transplant in the treatment of rhabdoid tumors will be published separately. PMID- 11782396 TI - Morphogenetic pattern formation during ascidian notochord formation is regulative and highly robust. AB - The ascidian notochord forms through simultaneous invagination and convergent extension of a monolayer epithelial plate. Here we combine micromanipulation with time lapse and confocal microscopy to examine how notochord-intrinsic morphogenetic behaviors and interactions with surrounding tissues, determine these global patterns of movement. We show that notochord rudiments isolated at the 64-cell stage divide and become motile with normal timing; but, in the absence of interactions with non-notochordal tissues, they neither invaginate nor converge and extend. We find that notochord formation is robust in the sense that no particular neighboring tissue is required for notochord formation. Basal contact with either neural plate or anterior endoderm/lateral mesenchyme or posterior mesoderm are each alone sufficient to ensure that the notochord plate forms and extends a cylindrical rod. Surprisingly, the axis of convergent extension depends on the specific tissues that contact the notochord, as do other patterns of cell shape change, movement and tissue deformation that accompany notochord formation. We characterize one case in detail, namely, embryos lacking neural plates, in which a normal notochord forms but by an entirely different trajectory. Our results show ascidian notochord formation to be regulative in a fashion and to a degree never before appreciated. They suggest this regulative behavior depends on a complex interplay between morphogenetic tendencies intrinsic to the notochord plate and instructive and permissive interactions with surrounding tissues. We discuss mechanisms that could account for these data and what they imply about notochord morphogenesis and its evolution within the chordate phylum. PMID- 11782397 TI - Polarized basolateral cell motility underlies invagination and convergent extension of the ascidian notochord. AB - We use 3D time-lapse analysis of living embryos and laser scanning confocal reconstructions of fixed, staged, whole-mounted embryos to describe three dimensional patterns of cell motility, cell shape change, cell rearrangement and tissue deformation that accompany formation of the ascidian notochord. We show that notochord formation involves two simultaneous processes occurring within an initially monolayer epithelial plate: The first is invagination of the notochord plate about the axial midline to form a solid cylindrical rod. The second is mediolaterally directed intercalation of cells within the plane of the epithelial plate, and then later about the circumference of the cylindrical rod, that accompanies its extension along the anterior/posterior (AP) axis. We provide evidence that these shape changes and rearrangements are driven by active extension of interior basolateral notochord cell edges directly across the faces of their adjacent notochord neighbors in a manner analogous to leading edge extension of lamellapodia by motile cells in culture. We show further that local edge extension is polarized with respect to both the AP axis of the embryo and the apicobasal axis of the notochord plate. Our observations suggest a novel view of how active basolateral motility could drive both invagination and convergent extension of a monolayer epithelium. They further reveal deep similarities between modes of notochord morphogenesis exhibited by ascidians and other chordate embryos, suggesting that cellular mechanisms of ascidian notochord formation may operate across the chordate phylum. PMID- 11782398 TI - Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target. AB - Migration of primordial germ cells (PGCs) from their site of specification towards the developing gonad is controlled by directional cues from somatic tissues. Although in several animals the PGCs are attracted by signals emanating from their final target, the gonadal mesoderm, little is known about the mechanisms that control earlier steps of migration. We provide evidence that a key step of zebrafish PGC migration, in which the PGCs become organized into bilateral clusters in the anterior trunk, is regulated by attraction of PGCs towards an intermediate target. Time-lapse observations of wild-type and mutant embryos reveal that bilateral clusters are formed at early somitogenesis, owing to migration of PGCs towards the clustering position from medial, posterior and anterior regions. Furthermore, PGCs migrate actively relative to their somatic neighbors and they do so as individual cells. Using mutants that exhibit defects in mesoderm development, we show that the ability to form PGC clusters depends on proper differentiation of the somatic cells present at the clustering position. Based on these findings, we propose that these somatic cells produce signals that attract PGCs. Interestingly, fate-mapping shows that these cells do not give rise to the somatic tissues of the gonad, but rather contribute to the formation of the pronephros. Thus, the putative PGC attraction center serves as an intermediate target for PGCs, which later actively migrate towards a more posterior position. This final step of PGC migration is defective in hands off mutants, where the intermediate mesoderm of the presumptive gonadal region is mispatterned. Our results indicate that zebrafish PGCs are guided by attraction towards two signaling centers, one of which may represent the somatic tissues of the gonad. PMID- 11782399 TI - Beta-catenin, MAPK and Smad signaling during early Xenopus development. AB - Knowledge of when and where signaling pathways are activated is crucial for understanding embryonic development. In this study, we have systematically analyzed and compared the signaling pattern of four major pathways by localization of the activated key components beta-catenin (Wnt proteins), MAPK (tyrosine kinase receptors/FGF), Smad1 (BMP proteins) and Smad2 (Nodal/activin/Vg1). We have determined semi-quantitatively the distribution of these components at 18 consecutive stages in Xenopus development, from early blastula to tailbud stages, by immunofluorescence on serial cryosections. The image obtained is that of very dynamic and widespread activities, with very few inactive regions. Signaling fields can vary from large gradients to restricted areas with sharp borders. They do not respect tissue boundaries. This direct visualization of active signaling verifies several predictions inferred from previous functional data. It also reveals unexpected signal patterns, pointing to some poorly understood aspects of early development. In several instances, the patterns strikingly overlap, suggesting extensive interplay between the various pathways. To test this possibility, we have manipulated maternal beta-catenin signaling and determined the effect on the other pathways in the blastula embryo. We found that the patterns of P-MAPK, P-Smad1 and P-Smad2 are indeed strongly dependent on beta-catenin at this stage. PMID- 11782400 TI - Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. AB - The mouse develops five pairs of mammary glands that arise during mid-gestation from five pairs of placodes of ectodermal origin. We have investigated the molecular mechanisms of mammary placode development using Lef1 as a marker for the epithelial component of the placode, and mice deficient for Fgf10 or Fgfr2b, both of which fail to develop normal mammary glands. Mammary placode induction involves two different signaling pathways, a FGF10/FGFR2b-dependent pathway for placodes 1, 2, 3 and 5 and a FGF10/FGFR2b-independent pathway for placode 4. Our results also suggest that FGF signaling is involved in the maintenance of mammary bud 4, and that Fgf10 deficient epithelium can undergo branching morphogenesis into the mammary fat pad precursor. PMID- 11782401 TI - Specific heparan sulfate structures involved in retinal axon targeting. AB - Heparan sulfate (HS), a structurally diverse molecule comprising distinct sequences of sulfated disaccharide units, is abundant in the developing brain and binds to axon guidance molecules. Addition of HS to the developing Xenopus optic pathway causes severe targeting errors yet it is not known how the structural diversity of this molecule relates to its role in axon guidance. We have used an in vivo brain assay to identify the structural characteristics of HS that induce aberrant axon targeting. Inhibiting sulfation of endogenous HS with chlorate causes axons to bypass their target, the tectum, and treatment with chemically modified heparins reveals that 2-O- and 6-O-sulfate groups have potent bypass inducing activity. Experiments with purified heparin saccharides show that bypass inducing activity correlates with distinct structures, particularly those containing a combination of 2-O- and 6-O-sulfate groups. Taken together the results indicate that specific sequences, rather than gross structural composition, are critical for activity. In situ hybridisation revealed that HS 6 O-sulfotransferase is regionally expressed along the border of the dorsal optic tract whereas 2-O-sulfotransferase is expressed broadly. Our results demonstrate that specific HS sequences are essential for regulating retinotectal axon targeting and suggest that regionalised biosynthesis of specific HS structures is important for guiding axons into the tectum. PMID- 11782402 TI - MASK, a large ankyrin repeat and KH domain-containing protein involved in Drosophila receptor tyrosine kinase signaling. AB - The receptor tyrosine kinases Sevenless (SEV) and the Epidermal growth factor receptor (EGFR) are required for the proper development of the Drosophila eye. The protein tyrosine phosphatase Corkscrew (CSW) is a common component of many RTK signaling pathways, and is required for signaling downstream of SEV and EGFR. In order to identify additional components of these signaling pathways, mutations that enhanced the phenotype of a dominant negative form of Corkscrew were isolated. This genetic screen identified the novel signaling molecule MASK, a large protein that contains two blocks of ankyrin repeats as well as a KH domain. MASK genetically interacts with known components of these RTK signaling pathways. In the developing eye imaginal disc, loss of MASK function generates phenotypes similar to those generated by loss of other components of the SEV and EGFR pathways. These phenotypes include compromised photoreceptor differentiation, cell survival and proliferation. Although MASK is localized predominantly in the cellular cytoplasm, it is not absolutely required for MAPK activation or nuclear translocation. Based on our results, we propose that MASK is a novel mediator of RTK signaling, and may act either downstream of MAPK or transduce signaling through a parallel branch of the RTK pathway. PMID- 11782403 TI - Early subdivisions in the neural plate define distinct competence for inductive signals. AB - Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying the regionally distinct competence for two such organizing signals, Fibroblast growth factor 8 (Fgf8) and Sonic hedgehog (Shh), using chick embryos. First, we demonstrated that FGF receptor 1 (Fgfr1) and Fgfr3, expressed differentially in the developing brain, possess an equivalent potential to induce the regionally distinct Fgf8-responsive genes, depending on the anterior-posterior dimension of the brain. Next we found that homeodomain transcription factors Six3 and Irx3 can alter the regional responses to both Fgf8 and Shh in the forebrain. Six3 confers the ability to express Bf1, a gene essential for the telencephalon and eye development, and Nkx2.1, which is required for development of the hypothalamus. In contrast, Irx3 confers the ability to express En2 and Nkx6.1 in response to Fgf8 and Shh, respectively. Furthermore, an alteration in the region-specific response to Fgf8 upon misexpression of Irx3 resulted in transformation of diencephalic and possibly telencephalic tissues into the optic tectum. Finally, we demonstrated that Six3 and Irx3 can mutually repress their expression, which may contribute to the establishment of their complementary expression domains in the neural plate. These repressive interactions are specific, as Six3 did not repress Gbx2, and Irx3 did not disturb Otx2 expression. These findings provide evidence that the early embryonic forebrain is demarcated into two domains with distinct genetic programs, which argues against the authentic telendiencephalic subdivision. PMID- 11782404 TI - Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. AB - To examine the consequences of repressing beta-catenin/Lef1 signalling in mouse epidermis, we expressed a DeltaNLef1 transgene, which lacks the beta-catenin binding site, under the control of the keratin 14 promoter. No skin abnormalities were detected before the first postnatal hair cycle. However, from 6 weeks of age, mice underwent progressive hair loss which correlated with the development of dermal cysts. The cysts were derived from the base of the hair follicles and expressed morphological and molecular markers of interfollicular epidermis. Adult mice developed spontaneous skin tumours, most of which exhibited sebaceous differentiation, which could be indicative of an origin in the upper part of the hair follicle. The transgene continued to be expressed in the tumours and beta catenin signalling was still inhibited, as evidenced by absence of cyclin D1 expression. However, patched mRNA expression was upregulated, suggesting that the sonic hedgehog pathway might play a role in tumour formation. Based on our results and previous data on the consequences of activating beta-catenin/Lef1 signalling in postnatal keratinocytes, we conclude that the level of beta-catenin signalling determines whether keratinocytes differentiate into hair or interfollicular epidermis, and that perturbation of the pathway by overexpression of DeltaNLef1 can lead to skin tumour formation. PMID- 11782405 TI - Clonal separation and regionalisation during formation of the medial and lateral myotomes in the mouse embryo. AB - In vertebrates, muscles of the back (epaxial) and of the body wall and limbs (hypaxial) derive from precursor cells located in the dermomyotome of the somites. In this paper, we investigate the mediolateral regionalisation of epaxial and hypaxial muscle precursor cells during segmentation of the paraxial mesoderm and myotome formation, using mouse LaacZ/LacZ chimeras. We demonstrate that precursors of medial and lateral myotomes are clonally separated in the mouse somite, consistent with earlier studies in birds. This clonal separation occurs after segmentation of the paraxial mesoderm. We then show that myotome precursors are mediolaterally regionalised and that this regionalisation precedes clonal separation between medial and lateral precursors. Strikingly, the properties of myotome precursors are remarkably similar in the medial and lateral domains. Finally, detailed analysis of our clones demonstrates a direct spatial relationship between the myocytes in the myotome and their precursors in the dermomyotome, and earlier in the somite and presomitic mesoderm, refuting several models of myotome formation, based on permanent stem cell systems or extensive cell mingling. This progressive mediolateral regionalisation of the myotome at the cellular level correlates with progressive changes in gene expression in the dermomyotome and myotome. PMID- 11782406 TI - Cell specification in the Arabidopsis root epidermis requires the activity of ECTOPIC ROOT HAIR 3--a katanin-p60 protein. AB - The Arabidopsis root is composed of radial cell layers, each with distinct identities. The epidermal layer is composed of rows of hair cells flanked on either side by rows of non-hair epidermal cells. The development of hair and non hair cells is dependent on domains of positional information with strict boundaries. The pattern of cell differentiation and the expression of molecular markers of cell fate is altered in the ectopic root hair 3 (erh3) mutant epidermis indicating that ERH3 is required for the specification of cell fates from early in development (in the meristem) through differentiation. Furthermore the expression of molecular markers indicates that the specification of cell identities is defective within other radial cell layers. ERH3 encodes a p60 katanin protein that is expressed throughout the plant. Katanin proteins are known to sever microtubules, and have a role in the organisation of the plant cell wall since mutants with decreased katanin activity have been shown to have defective walls. We suggest that microtubules are involved in the specification of cell identities in cells of the Arabidopsis root. Microtubules may be required for the localization of positional cues in the wall that have previously been shown to operate in the development of the root epidermis. Alternatively microtubules may be involved in another as yet undefined process required for the specification of cell identity in plants. PMID- 11782407 TI - myoblasts incompetent encodes a zinc finger transcription factor required to specify fusion-competent myoblasts in Drosophila. AB - We report a new gene, myoblasts incompetent, essential for normal myogenesis and myoblast fusion in Drosophila. myoblasts incompetent encodes a putative zinc finger transcription factor related to vertebrate Gli proteins and to Drosophila Cubitus interruptus. myoblasts incompetent is expressed in immature somatic and visceral myoblasts. Expression is predominantly in fusion-competent myoblasts and a loss-of-function mutation in myoblasts incompetent leads to a failure in the normal differentiation of these cells and a complete lack of myoblast fusion. In the mutant embryos, founder myoblasts differentiate normally and form mononucleate muscles, but genes that are specifically expressed in fusion competent cells are not activated and the normal downregulation of twist expression in these cells fails to occur. In addition, fusion-competent myoblasts fail to express proteins characteristic of the general pathway of myogenesis such as myosin and Dmef2. Thus myoblasts incompetent appears to function specifically in the general pathway of myogenesis to control the differentiation of fusion competent myoblasts. PMID- 11782408 TI - Eyes closed, a Drosophila p47 homolog, is essential for photoreceptor morphogenesis. AB - Starting with a mutation impacting photoreceptor morphogenesis, we identify here a Drosophila gene, eyes closed (eyc), as a fly homolog of p47, a protein co factor of the p97 ATPase implicated in membrane fusion. Temporal misexpression of Eyc during rhabdomere extension early in pupal life results in inappropriate retention of normally transient adhesions between developing rhabdomeres. Later Eyc misexpression results in endoplasmic reticulum proliferation and inhibits rhodopsin transport to the developing photosensitive membrane. Loss of Eyc function results in a lethal failure of nuclear envelope assembly in early zygotic divisions. Phenotypes resulting from eyc mutations provide the first in vivo evidence for a role for p47 in membrane biogenesis. PMID- 11782409 TI - Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development. AB - In Schwann cells (SC), myelination is controlled by the transcription factor gene Krox20/Egr2. Analysis of cis-acting elements governing Krox20 expression in SC revealed the existence of two separate elements. The first, designated immature Schwann cell element (ISE), was active in immature but not myelinating SC, whereas the second, designated myelinating Schwann cell element (MSE), was active from the onset of myelination to adulthood in myelinating SC. In vivo sciatic nerve regeneration experiments demonstrated that both elements were activated during this process, in an axon-dependent manner. Together the activity of these elements reproduced the profile of Krox20 expression during development and regeneration. Genetic studies showed that both elements were active in a Krox20 mutant background, while the activity of the MSE, but likely not of the ISE, required the POU domain transcription factor Oct6 at the time of myelination. The MSE was localised to a 1.3 kb fragment, 35 kb downstream of Krox20. The identification of multiple Oct6 binding sites within this fragment suggested that Oct6 directly controls Krox20 transcription. Taken together, these data indicate that, although Krox20 is expressed continuously from 15.5 dpc in SC, the regulation of its expression is a biphasic, axon-dependent phenomenon involving two cis-acting elements that act in succession during development. In addition, they provide insight into the complexity of the transcription factor regulatory network controlling myelination. PMID- 11782410 TI - Disruption of Gja8 (alpha8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation. AB - The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, alpha8 (Cx50), alpha3 (Cx46) and alpha1 (Cx43), and which are encoded by three different genes. In a previous study, we reported that, with a disruption of Gja3 (alpha3 connexin), mice developed nuclear cataracts with a normal sized lens. We show that Gja8tm1 (alpha8-/-) mice develop microphthalmia with small lenses and nuclear cataracts, while the alpha8 heterozygous (+/-) mice have relatively normal eyes and lenses. A comparative study of these alpha3 and alpha8 knockout mice showed that the protein levels of both alpha3 and alpha8 were independently regulated and there was no compensation for either the alpha3 or alpha8 protein from the wild-type allele when the other allele was disrupted. More interestingly, western blotting data indicated that the presence of alpha8 in the lens nucleus is dependent on alpha3 connexin, but not vice versa. The staining of the knock-in lacZ reporter gene showed the promoter activity of alpha8 connexin is much higher than that of alpha3 connexin in embryonic lenses and in adult lens epithelium. More importantly, a delayed denucleation process was observed in the interior fibers of the alpha8-/- lenses. Therefore, alpha8 connexin is required for proper fiber cell maturation and control of lens size. PMID- 11782411 TI - Mechanism of activation of the Drosophila EGF Receptor by the TGFalpha ligand Gurken during oogenesis. AB - We have analyzed the mechanism of activation of the Epidermal growth factor receptor (Egfr) by the transforming growth factor (TGF) alpha-like molecule, Gurken (Grk). Grk is expressed in the oocyte and activates the Egfr in the surrounding follicle cells during oogenesis. We show that expression of either a membrane bound form of Grk (mbGrk), or a secreted form of Grk (secGrk), in either the follicle cells or in the germline, activates the Egfr. In tissue culture cells, both forms can bind to the Egfr; however, only the soluble form can trigger Egfr signaling, which is consistent with the observed cleavage of Grk in vivo. We find that the two transmembrane proteins Star and Brho potentiate the activity of mbGrk. These two proteins collaborate to promote an activating proteolytic cleavage and release of Grk. After cleavage, the extracellular domain of Grk is secreted from the oocyte to activate the Egfr in the follicular epithelium. PMID- 11782412 TI - The stem-loop binding protein CDL-1 is required for chromosome condensation, progression of cell death and morphogenesis in Caenorhabditis elegans. AB - Histones play important roles not only in the structural changes of chromatin but also in regulating gene expression. Expression of histones is partly regulated post-transcriptionally by the stem-loop binding protein (SLBP)/hairpin binding protein (HBP). We report the developmental function of CDL-1, the C. elegans homologue of SLBP/HBP. In the C. elegans cdl-1 mutants, cell corpses resulting from programmed cell death appear later and persist much longer than those in the wild type. They also exhibit distinct morphological defects in body elongation and movement of the pharyngeal cells toward the buccal opening. The CDL-1 protein binds to the stem-loop structures in the 3'-UTR of C. elegans core histone mRNAs, and the mutant forms of this protein show reduced binding activities. A decrease in the amount of core histone proteins phenocopied the cdl-1 mutant embryos, suggesting that CDL-1 contributes to the proper expression of core histone proteins. We propose that loss-of-function of cdl-1 causes aberrant chromatin structure, which affects the cell cycle and cell death, as well as transcription of genes essential for morphogenesis. PMID- 11782413 TI - Ypsilon Schachtel, a Drosophila Y-box protein, acts antagonistically to Orb in the oskar mRNA localization and translation pathway. AB - Subcellular localization of mRNAs within the Drosophila oocyte is an essential step in body patterning. Yps, a Drosophila Y-box protein, is a component of an ovarian ribonucleoprotein complex that also contains Exu, a protein that plays an essential role in mRNA localization. Y-box proteins are known translational regulators, suggesting that this complex might regulate translation as well as mRNA localization. Here we examine the role of the yps gene in these events. We show that yps interacts genetically with orb, a positive regulator of oskar mRNA localization and translation. The nature of the genetic interaction indicates that yps acts antagonistically to orb. We demonstrate that Orb protein is physically associated with both the Yps and Exu proteins, and that this interaction is mediated by RNA. We propose a model wherein Yps and Orb bind competitively to oskar mRNA with opposite effects on translation and RNA localization. PMID- 11782414 TI - Specification and determination of limb identity: evidence for inhibitory regulation of Tbx gene expression. AB - Limb-type-specific expression of Tbx5/Tbx4 plays a key role in drawing distinction between a forelimb and a hindlimb. Here, we show insights into specification and determination during commitment of limb-type identity, in particular that median tissues regulate Tbx expressions. By using the RT-PCR technique on chick embryos, the onset of specific Tbx5/Tbx4 expression in the wing/leg region was estimated to be stage 13. Specification of the limb-type identity is thought to occur before stage 9, since all explants from stage 9 through 14 expressed the intrinsic Tbx gene autonomously in a simple culture medium. The results of transplantation experiments revealed that axial structures medial to the lateral plate mesoderm at the level of the wing region are capable of transforming leg identity to wing identity, suggesting that a factor(s) from the median tissues is involved in the limb-type determination. Nevertheless, the transplanted wing region was not converted to leg identity. The results of the transplantation experiments also suggested that wing-type identity is determined much earlier than is leg-type identity. Finally, we also found that inhibitory effects of median tissues mediate the specific expression of Tbx5/Tbx4 in the presumptive wing/leg region. We propose a model for limb-type identification in which inhibitory regulation is involved in restricting one Tbx gene expression by masking the other Tbx expression there. PMID- 11782415 TI - DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity. AB - The daf-9 gene functions to integrate transforming growth factor-beta and insulin like signaling pathways to regulate Caenorhabditis elegans larval development. Mutations in daf-9 result in transient dauer-like larval arrest, abnormal reproductive development, molting defects and increased adult longevity. The phenotype is sterol-dependent, and dependent on the activity of DAF-12, a nuclear hormone receptor. Genetic tests show that daf-9 is upstream of daf-12 in the genetic pathways for larval development and adult longevity. daf-9 encodes a cytochrome P450 related to those involved in biosynthesis of steroid hormones in mammals. We propose that it specifies a step in the biosynthetic pathway for a DAF-12 ligand, which might be a steroid. The surprising cellular specificity of daf-9 expression (predominantly in two sensory neurons) supports a previously unrecognized role for these cells in neuroendocrine control of larval development, reproduction and life span. PMID- 11782416 TI - Neural stem cell lineages are regionally specified, but not committed, within distinct compartments of the developing brain. AB - Regional patterning in the developing mammalian brain is partially regulated by restricted gene expression patterns within the germinal zone, which is composed of stem cells and their progenitor cell progeny. Whether or not neural stem cells, which are considered at the top of the neural lineage hierarchy, are regionally specified remains unknown. Here we show that the cardinal properties of neural stem cells (self-renewal and multipotentiality) are conserved among embryonic cortex, ganglionic eminence and midbrain/hindbrain, but that these different stem cells express separate molecular markers of regional identity in vitro, even after passaging. Neural stem cell progeny derived from ganglionic eminence but not from other regions are specified to respond to local environmental cues to migrate ventrolaterally, when initially deposited on the germinal layer of ganglionic eminence in organotypic slice cultures. Cues exclusively from the ventral forebrain in a 5 day co-culture paradigm could induce both early onset and late onset marker gene expression of regional identity in neural stem cell colonies derived from both the dorsal and ventral forebrain as well as from the midbrain/hindbrain. Thus, neural stem cells and their progeny are regionally specified in the developing brain, but this regional identity can be altered by local inductive cues. PMID- 11782417 TI - Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. AB - The expression of the Dlx homeobox genes is closely associated with neurons that express gamma-aminobutyric acid (GABA) in the embryonic rostral forebrain. To test whether the Dlx genes are sufficient to induce some aspects of the phenotype of GABAergic neurons, we adapted the electroporation method to ectopically express DLX proteins in slice cultures of the mouse embryonic cerebral cortex. This approach showed that ectopic expression of Dlx2 and Dlx5 induced the expression of glutamic acid decarboxylases (GADs), the enzymes that synthesize GABA. We also used this method to show cross-regulation between different Dlx family members. We find that Dlx2 can induce Dlx5 expression, and that Dlx1, Dlx2 and Dlx5 can induce expression from a Dlx5/6-lacZ enhancer/"reporter construct. PMID- 11782418 TI - SEUSS, a member of a novel family of plant regulatory proteins, represses floral homeotic gene expression with LEUNIG. AB - Proper regulation of homeotic gene expression is critical for pattern formation during both animal and plant development. A negative regulatory mechanism ensures that the floral homeotic gene AGAMOUS is only expressed in the center of an Arabidopsis floral meristem to specify stamen and carpel identity and to repress further proliferation of the floral meristem. We report the genetic identification and characterization of a novel gene, SEUSS, that is required in the negative regulation of AGAMOUS. Mutations in SEUSS cause ectopic and precocious expression of AGAMOUS mRNA, leading to partial homeotic transformation of floral organs in the outer two whorls. The effects of seuss mutations are most striking when combined with mutations in LEUNIG, a previously identified repressor of AGAMOUS. More complete homeotic transformation of floral organs and a greater extent of organ loss in all floral whorls were observed in the seuss leunig double mutants. By in situ hybridization and double and triple mutant analyses, we showed that this enhanced defect was caused by an enhanced ectopic and precocious expression of AGAMOUS. Using a map-based approach, we isolated the SEUSS gene and showed that it encodes a novel protein with at least two glutamine rich domains and a highly conserved domain that shares sequence identity with the dimerization domain of the LIM-domain-binding transcription co-regulators in animals. Based on these molecular and genetic analyses, we propose that SEUSS encodes a regulator of AGAMOUS and functions together with LEUNIG. PMID- 11782419 TI - A rice heterochronic mutant, mori1, is defective in the juvenile-adult phase change. AB - We have identified five recessive allelic mutations, mori1-1 to mori1-5, which drastically modify the shoot architecture of rice. The most remarkable feature of mori1 plants is a rapid production of small leaves and short branches. The mori1 plants are about 5 cm in height even 7 months after sowing. No reproductive growth was attained in mori1 plants even if inductive short-day treatment was applied. Leaves of mori1 at any position were very small and the size and shape were comparable to those of the wild-type 2nd leaf. The stem of mori1 7 months after sowing did not differentiate node and internode and had randomly oriented vascular bundles, which were characteristic of the basal part of the wild-type stem where 2nd and 3rd leaves were inserted. These structural characteristics indicate that mori1 maintains the 2nd-leaf stage (juvenile phase) of the wild type. The short plastochron and high cell division activity in the shoot apical meristem further confirmed the juvenility of mori1, corresponding to the 2nd-leaf differentiation stage in the wild-type embryo. Furthermore, the apparent photosynthetic rate in mori1 leaves was low as in the wild-type 2nd leaf. Thus, mori1 is a heterochronic mutation that suppresses the induction of adult phase and the termination of the juvenile phase. Therefore, MORI1 plays an important role in the juvenile-adult phase change. The importance of heterochronic mutations in modifying shoot architecture is discussed. PMID- 11782420 TI - Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber. AB - Reovirus attaches to cellular receptors with the sigma1 protein, a fiber-like molecule protruding from the 12 vertices of the icosahedral virion. The crystal structure of a receptor-binding fragment of sigma1 reveals an elongated trimer with two domains: a compact head with a new beta-barrel fold and a fibrous tail containing a triple beta-spiral. Numerous structural and functional similarities between reovirus sigma1 and the adenovirus fiber suggest an evolutionary link in the receptor-binding strategies of these two viruses. A prominent loop in the sigma1 head contains a cluster of residues that are conserved among reovirus serotypes and are likely to form a binding site for junction adhesion molecule, an integral tight junction protein that serves as a reovirus receptor. The fibrous tail is mainly responsible for sigma1 trimer formation, and it contains a highly flexible region that allows for significant movement between the base of the tail and the head. The architecture of the trimer interface and the observed flexibility indicate that sigma1 is a metastable structure poised to undergo conformational changes upon viral attachment and cell entry. PMID- 11782421 TI - Cooperative kinetics of both Hsp104 ATPase domains and interdomain communication revealed by AAA sensor-1 mutants. AB - AAA proteins share a conserved active site for ATP hydrolysis and regulate many cellular processes. AAA proteins are oligomeric and often have multiple ATPase domains per monomer, which is suggestive of complex allosteric kinetics of ATP hydrolysis. Here, using wild-type Hsp104 in the hexameric state, we demonstrate that its two AAA modules (NBD1 and NBD2) have very different catalytic activities, but each displays cooperative kinetics of hydrolysis. Using mutations in the AAA sensor-1 motif of NBD1 and NBD2 that reduce the rate of ATP hydrolysis without affecting nucleotide binding, we also examine the consequences of keeping each site in the ATP-bound state. In vitro, reducing k(cat) at NBD2 significantly alters the steady-state kinetic behavior of NBD1. Thus, Hsp104 exhibits allosteric communication between the two sites in addition to homotypic cooperativity at both NBD1 and NBD2. In vivo, each sensor-1 mutation causes a loss-of-function phenotype in two assays of Hsp104 function (thermotolerance and yeast prion propagation), demonstrating the importance of ATP hydrolysis as distinct from ATP binding at each site for Hsp104 function. PMID- 11782422 TI - Plasmodium falciparum activates endogenous Cl(-) channels of human erythrocytes by membrane oxidation. AB - Intraerythrocytic survival of the malaria parasite Plasmodium falciparum requires that host cells supply nutrients and dispose of waste products. This solute transport is accomplished by infection-induced new permeability pathways (NPP) in the erythrocyte membrane. Here, whole-cell patch-clamp and hemolysis experiments were performed to define properties of the NPP. Parasitized but not control erythrocytes constitutively expressed two types of anion conductances, differing in voltage dependence and sensitivity to inhibitors. In addition, infected but not control cells hemolyzed in isosmotic sorbitol solution. Both conductances and hemolysis of infected cells were inhibited by reducing agents. Conversely, oxidation induced identical conductances and hemolysis in non-infected erythrocytes. In conclusion, P.falciparum activates endogenous erythrocyte channels by applying oxidative stress to the host cell membrane. PMID- 11782423 TI - A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis. AB - INI1 (integrase interactor 1)/hSNF5 is a component of the mammalian SWI/SNF complex and a tumor suppressor mutated in malignant rhabdoid tumors (MRT). We have identified a nuclear export signal (NES) in the highly conserved repeat 2 domain of INI1 that is unmasked upon deletion of a downstream sequence. Mutation of conserved hydrophobic residues within the NES, as well as leptomycin B treatment abrogated the nuclear export. Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro. A mutant INI1 [INI1(1-319) delG950] found in MRT lacking the 66 C-terminal amino acids mislocalized to the cytoplasm. Full-length INI1 but not the INI1(1-319 delG950) mutant caused flat cell formation and cell cycle arrest in cell lines derived from MRT. Disruption of the NES in the delG950 mutant caused nuclear localization of the protein and restored its ability to cause cell cycle arrest. These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis. PMID- 11782424 TI - Shy1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh's syndrome. AB - SHY1 codes for a mitochondrial protein required for full expression of cytochrome oxidase (COX) in Saccharomyces cerevisiae. Mutations in the homologous human gene (SURF1) have been reported to cause Leigh's syndrome, a neurological disease associated with COX deficiency. The function of Shy1p/Surf1p is poorly understood. Here we have characterized revertants of shy1 null mutants carrying extragenic nuclear suppressor mutations. The steady-state levels of COX in the revertants is increased by a factor of 4-5, accounting for their ability to respire and grow on non-fermentable carbon sources at nearly wild-type rates. The suppressor mutations are in MSS51, a gene previously implicated in processing and translation of the COX1 transcript for subunit 1 (Cox1) of COX. The function of Shy1p and the mechanism of suppression of shy1 mutants were examined by comparing the rates of synthesis and turnover of the mitochondrial translation products in wild-type, mutant and revertant cells. We propose that Shy1p promotes the formation of an assembly intermediate in which Cox1 is one of the partners. PMID- 11782425 TI - CREB activation induced by mitochondrial dysfunction is a new signaling pathway that impairs cell proliferation. AB - We characterized a new signaling pathway leading to the activation of cAMP responsive element-binding protein (CREB) in several cell lines affected by mitochondrial dysfunction. In vitro kinase assays, inhibitors of several kinase pathways and overexpression of a dominant-negative mutant for calcium/calmodulin kinase IV (CaMKIV), which blocks the activation of CREB, showed that CaMKIV is activated by a mitochondrial activity impairment. A high calcium concentration leading to the disruption of the protein interaction with protein phosphatase 2A explains CaMKIV activation in these conditions. Transcrip tionally active phosphorylated CREB was also found in a rho0 143B human osteosarcoma cell line and in a MERRF cybrid cell line mutated for tRNA(Lys) (A8344G). We also showed that phosphorylated CREB is involved in the proliferation defect induced by a mitochondrial dysfunction. Indeed, cell proliferation inhibition can be prevented by CaMKIV inhibition and CREB dominant-negative mutants. Finally, our data suggest that phosphorylated CREB recruits p53 tumor suppressor protein, modifies its transcriptional activity and increases the expression of p21(Waf1/Cip1), a p53-regulated cyclin-dependent kinase inhibitor. PMID- 11782426 TI - Regulation of Raf-1 activation and signalling by dephosphorylation. AB - The Raf-1 kinase is regulated by phosphorylation, and Ser259 has been identified as an inhibitory phosphorylation site. Here we show that the dephosphorylation of Ser259 is an essential part of the Raf-1 activation process, and further reveal the molecular role of Ser259. The fraction of Raf-1 that is phosphorylated on Ser259 is refractory to mitogenic stimulation. Mutating Ser259 elevates kinase activity because of enhanced binding to Ras and constitutive membrane recruitment. This facilitates the phosphorylation of an activating site, Ser338. The mutation of Ser259 also increases the functional coupling to MEK, augmenting the efficiency of MEK activation. Our results suggest that Ser259 regulates the coupling of Raf-1 to upstream activators as well as to its downstream substrate MEK, thus determining the pool of Raf-1 that is competent for signalling. They also suggest a new model for Raf-1 activation where the release of repression through Ser259 dephosphorylation is the pivotal step. PMID- 11782427 TI - PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2. AB - Heregulin (HRG)-induced tyrosine phosphorylation of the Gab2 docking protein was enhanced by pretreatment with wortmannin, indicating negative regulation via a PI3-kinase-dependent pathway. This represents phosphorylation by the serine/threonine kinase protein kinase B (PKB), since PKB constitutively associates with Gab2, phosphorylates Gab2 on a consensus phosphorylation site, Ser159, in vitro and inhibits Gab2 tyrosine phosphorylation. However, expression of Gab2 mutated at this site (S159A Gab2) not only enhanced HRG-induced Gab2 tyrosine phosphorylation and association with Shc and ErbB2, but also markedly increased tyrosine phosphorylation of ErbB2 and other cellular proteins and amplified activation of the ERK and PKB pathways. The impact of this negative regulation was further emphasized by a potent transforming activity for S159A Gab2, but not wild-type Gab2, in fibroblasts. These studies establish Gab2 as a proto-oncogene, and a model in which receptor recruitment of Gab2 is tightly regulated via an intimate association with PKB. Release of this negative constraint enhances growth factor receptor signalling, possibly since Gab2 binding limits dephosphorylation and disassembly of receptor-associated signalling complexes. PMID- 11782428 TI - BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor. AB - B-cell activation mediated through the antigen receptor is dependent on activation of protein tyrosine kinases (PTKs) such as Lyn and Syk and subsequent phosphorylation of various signaling proteins. Here we report on the identification and characterization of the B-cell scaffold protein with ankyrin repeats (BANK), a novel substrate of tyrosine kinases. BANK is expressed in B cells and is tyrosine phosphorylated upon B-cell antigen receptor (BCR) stimulation, which is mediated predominantly by Syk. Overexpres sion of BANK in B cells leads to enhancement of BCR-induced calcium mobilization. We found that both Lyn and inositol 1,4,5-trisphosphate receptor (IP(3)R) associate with the distinct regions of BANK and that BANK promotes Lyn-mediated tyrosine phosphorylation of IP(3)R. Given that IP(3)R channel activity is up-regulated by its tyrosine phosphorylation, BANK appears to be a novel scaffold protein regulating BCR-induced calcium mobilization by connecting PTKs to IP(3)R. Because BANK expression is confined to functional BCR-expressing B cells, BANK-mediated calcium mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development. PMID- 11782429 TI - LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation. AB - LNX is a RING finger and PDZ domain containing protein that interacts with the cell fate determinant Numb. To investigate the function of LNX, we tested its RING finger domain for ubiquitin ligase activity. The isolated RING finger domain was able to function as an E2-dependent, E3 ubiquitin ligase in vitro and mutation of a conserved cysteine residue within the RING domain abolished its activity, indicating that LNX is the first described PDZ domain-containing member of the E3 ubiquitin ligase family. We have identified Numb as a substrate of LNX E3 activity in vitro and in vivo. In addition to the RING finger, a region of LNX, including the Numb PTB domain-binding site and the first PDZ domain, is required for Numb ubiquitylation. Expression of wild-type but not mutant LNX causes proteasome-dependent degradation of Numb and can enhance Notch signalling. These results suggest that the levels of mammalian Numb protein and therefore, by extension, the processes of asymmetric cell division and cell fate determination may be regulated by ubiquitin-dependent proteolysis. PMID- 11782430 TI - IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors. AB - Mice that lack the transcription factors encoded by the E2A gene or the receptor for interleukin 7 (IL-7R) have severe overlapping defects in lymphocyte development. Here, we show that E2A proteins are required for the survival of early T-lineage cells; however, they function through a pathway that is distinct from the survival pathway initiated by IL-7R signaling. While E2A proteins are required to suppress caspase 3 activation, ectopic expression of the anti apoptotic protein Bcl-2 is not sufficient to overcome the lymphopoietic defects observed in the absence of E2A. Remarkably, mice that lack both IL-7Ralpha and E47 display a synergistic decrease in the number of T-cell, NK-cell and multipotent progenitors in the thymus, indicating that these distinct survival pathways converge to promote the development of multipotent lymphoid progenitors. PMID- 11782431 TI - BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation. AB - CDO is a cell surface receptor-like protein that positively regulates myogenic differentiation. Reported here is the identification of BOC, which, with CDO, defines a newly recognized subfamily within the immunoglobulin superfamily. cdo and boc are co-expressed in muscle precursors in the developing mouse embryo. Like CDO, BOC accelerates differentiation of cultured myoblast cell lines and participates in a positive feedback loop with the myogenic transcription factor, MyoD. CDO and BOC form complexes in a cis fashion via association of both their ectodomains and their intracellular domains. A soluble fusion protein that contains the entire BOC ectodomain functions similarly to full-length BOC to promote myogenic differentiation, indicating that the intracellular region is dispensable for its activity in this system. Furthermore, a dominant-negative form of CDO inhibits the pro-myogenic effects of soluble BOC, suggesting that BOC is dependent on CDO for its activity. CDO and BOC are proposed to be components of a receptor complex that mediates some of the cell-cell interactions between muscle precursors that are required for myogenesis. PMID- 11782432 TI - T-cell receptor sequences that elicit strong down-regulation of premature termination codon-bearing transcripts. AB - The nonsense-mediated decay (NMD) RNA surveillance pathway detects and degrades mRNAs containing premature termination codons (PTCs). T-cell receptor (TCR) and immunoglobulin transcripts, which commonly harbor PTCs as a result of programmed DNA rearrangement during normal development, are down-regulated much more than other known mammalian gene transcripts in response to nonsense codons. Here, we demonstrate that this is not because of promoter or cell type but instead is directed by regulatory sequences within the rearranging VDJ exon and immediately flanking intron sequences of a Vbeta8.1 TCR-beta gene. Insertion of these sequences into a heterologous gene elicited strong down-regulation (>30-fold) in response to PTCs, indicating that this region is sufficient to trigger robust down-regulation. The rearranging Vbeta5.1 exon and the flanking intron sequences from another member of the TCR-beta family also triggered strong down-regulation, suggesting that down-regulatory-promoting elements are a conserved feature of TCR genes. Importantly, we found that the Vbeta8.1 down-regulatory-promoting element was position dependent, such that it failed to function when positioned downstream of a PTC. To our knowledge, this is the first class of down-regulatory elements identified that act upstream of nonsense codons. PMID- 11782433 TI - Acute glucose starvation activates the nuclear localization signal of a stress specific yeast transcription factor. AB - In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism. PMID- 11782434 TI - Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif. AB - Transforming growth factor-beta (TGF-beta)/activin-induced Smad2/Smad4 complexes are recruited to different promoter elements by transcription factors, such as Fast-1 or the Mix family proteins Mixer and Milk, through a direct interaction between Smad2 and a common Smad interaction motif (SIM) in the transcription factors. Here we identify residues in the SIM critical for Mixer-Smad2 interaction and confirm their functional importance by demonstrating that only Xenopus and zebrafish Mix family members containing a SIM with all the correct critical residues can bind Smad2 and mediate TGF-beta-induced transcriptional activation in vivo. We identify significant sequence similarity between the SIM and the Smad-binding domain (SBD) of the membrane-associated protein SARA (Smad anchor for receptor activation). Molecular modelling, supported by mutational analyses of Smad2 and the SIM and the demonstration that the SARA SBD competes directly with the SIM for binding to Smad2, indicates that the SIM binds Smad2 in the same hydrophobic pocket as does the proline-rich rigid coil region of the SARA SBD. Thus, different Smad2 partners, whether cytoplasmic or nuclear, interact with the same binding pocket in Smad2 through a common proline-rich motif. PMID- 11782435 TI - In vivo RNA-directed transcription, with template switching, by a mammalian RNA polymerase. AB - These studies support the interpretation that a host polymerase, most likely RNA polymerase II, can not only carry out transcription that is RNA directed, but also achieve template switching on a discontinuous RNA template, and even perform non-templated nucleotide incorporation. As part of an in vivo analysis of the initiation of replication of the RNA genome of human hepatitis delta virus (HDV), a series of linear RNAs containing HDV sequences was tested in order to explain the ability of this host polymerase to initiate RNA-directed RNA synthesis in vivo and produce replicating circular HDV species. The data support the hypothesis that the input linear template RNAs were not converted to circles before transcription but rather that in the process of transcription, the polymerase was able to make an intra-molecular template switch. Furthermore, in certain cases this switch produced small deletions of template sequences, and in some cases even insertion of non-templated sequences. Thus, in an in vivo situation, polymerase II has several important capabilities in addition to what is considered typical DNA-directed transcription. PMID- 11782436 TI - The mammalian exosome mediates the efficient degradation of mRNAs that contain AU rich elements. AB - HeLa cytoplasmic extracts contain both 3'-5' and 5'-3' exonuclease activities that may play important roles in mRNA decay. Using an in vitro RNA deadenylation/decay assay, mRNA decay intermediates were trapped using phosphothioate-modified RNAs. These data indicate that 3'-5' exonucleolytic decay is the major pathway of RNA degradation following deadenylation in HeLa cytoplasmic extracts. Immunodepletion using antibodies specific for the exosomal protein PM-Scl75 demonstrated that the human exosome complex is required for efficient 3'-5' exonucleolytic decay. Furthermore, 3'-5' exonucleolytic decay was stimulated dramatically by AU-rich instability elements (AREs), implicating a role for the exosome in the regulation of mRNA turnover. Finally, PM-Scl75 protein was found to interact specifically with AREs. These data suggest that the interaction between the exosome and AREs plays a key role in regulating the efficiency of ARE-containing mRNA turnover. PMID- 11782437 TI - A role for RAD54B in homologous recombination in human cells. AB - In human somatic cells, homologous recombination is a rare event. To facilitate the targeted modification of the genome for research and gene therapy applications, efforts should be directed toward understanding the molecular mechanisms of homologous recombination in human cells. Although human genes homologous to members of the RAD52 epistasis group in yeast have been identified, no genes have been demonstrated to play a role in homologous recombination in human cells. Here, we report that RAD54B plays a critical role in targeted integration in human cells. Inactivation of RAD54B in a colon cancer cell line resulted in severe reduction of targeted integration frequency. Sensitivity to DNA-damaging agents and sister-chromatid exchange were not affected in RAD54B deficient cells. Parts of these phenotypes were similar to those of Saccharomyces cerevisiae tid1/rdh54 mutants, suggesting that RAD54B may be a human homolog of TID1/RDH54. In yeast, TID1/RDH54 acts in the recombinational repair pathway via roles partially overlapping those of RAD54. Our findings provide the first genetic evidence that the mitotic recombination pathway is functionally conserved from yeast to humans. PMID- 11782438 TI - Four new subunits of the Dam1-Duo1 complex reveal novel functions in sister kinetochore biorientation. AB - We show here that Ask1p, Dad2p, Spc19p and Spc34p are subunits of the budding yeast Duo1p-Dam1p- Dad1p complex, which associate with kinetochores and localize along metaphase and anaphase spindles. Analysis of spc34-3 cells revealed three novel functions of the Duo1-Dam1p-Dad1p subunit Spc34p. First, SPC34 is required to establish biorientation of sister kinetochores. Secondly, SPC34 is essential to maintain biorientation. Thirdly, SPC34 is necessary to maintain an anaphase spindle independently of chromosome segregation. Moreover, we show that in spc34 3 cells, sister centromeres preferentially associate with the pre-existing, old spindle pole body (SPB). A similar preferential attachment of sister centromeres to the old SPB occurs in cells depleted of the cohesin Scc1p, a protein with a known role in facilitating biorientation. Thus, the two SPBs are not equally active in early S phase. We suggest that not only in spc34-3 and Deltascc1 cells but also in wild-type cells, sister centromeres bind after replication preferentially to microtubules organized by the old SPB. Monopolar attached sister centromeres are resolved to bipolar attachment in wild-type cells but persist in spc34-3 cells. PMID- 11782439 TI - Becoming fat. PMID- 11782440 TI - DNA methylation patterns and epigenetic memory. PMID- 11782441 TI - C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. AB - PPARgamma and C/EBPalpha are critical transcription factors in adipogenesis, but the precise role of these proteins has been difficult to ascertain because they positively regulate each other's expression. Questions remain about whether these factors operate independently in separate, parallel pathways of differentiation, or whether a single pathway exists. PPARgamma can promote adipogenesis in C/EBPalpha-deficient cells, but the converse has not been tested. We have created an immortalized line of fibroblasts lacking PPARgamma, which we use to show that C/EBPalpha has no ability to promote adipogenesis in the absence of PPARgamma. These results indicate that C/EBPalpha and PPARgamma participate in a single pathway of fat cell development with PPARgamma being the proximal effector of adipogenesis. PMID- 11782442 TI - PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. AB - To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the gamma2-specific promoter, P2. In 3T3-L1 cells, expression of ZFP55 resulted in >50% reduction in gamma2 expression but had no effect on gamma1, whereas adipogenesis was similarly reduced by 50%. However, ZFP54 virtually abolished both gamma2 and gamma1 expression, and completely blocked adipogenesis. Overexpression of exogenous gamma2 in the ZFP54-expressing cells completely restored adipogenesis, whereas overexpression of gamma1 had no effect. This finding clearly identifies a unique role for the PPARgamma2 isoform. PMID- 11782443 TI - TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. AB - Recent reports suggest that a cross-talk exists between apoptosis pathways mediated by mitochondria and cell death receptors. In the present study, we report that mitochondrial events are required for apoptosis induced by the cell death ligand TRAIL (TNF-related apoptosis-inducing ligand) in human cancer cells. We show that the Bax null cancer cells are resistant to TRAIL-induced apoptosis. Bax deficiency has no effect on TRAIL-induced caspase-8 activation and subsequent cleavage of Bid; however, it results in an incomplete caspase-3 processing because of inhibition by XIAP. Release of Smac/DIABLO from mitochondria through the TRAIL-caspase-8-tBid-Bax cascade is required to remove the inhibitory effect of XIAP and allow apoptosis to proceed. Inhibition of caspase-9 activity has no effect on TRAIL-induced caspase-3 activation and cell death, whereas expression of the active form of Smac/DIABLO in the cytosol is sufficient to reconstitute TRAIL sensitivity in Bax-deficient cells. Our results show for the first time that Bax-dependent release of Smac/DIABLO, not cytochrome c, from mitochondria mediates the contribution of the mitochondrial pathway to death receptor-mediated apoptosis. PMID- 11782444 TI - WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. AB - WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich, heparin-binding, secreted proteins associated with the extracellular matrix, and can interact with cellular integrins. Expression of WISP-1 in some cells results in transformation and tumorigenesis. Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. It also is demonstrated that WISP-1 can prevent cells from undergoing apoptosis following DNA damage through inhibition of the mitochondrial release of cytochrome c and up-regulation of antiapoptotic Bcl-X(L). Furthermore, the results show that WISP-1 protects cells from p53-dependent cell death, but not Fas-ligand activated cell death, suggesting that there may be cross talk between the tumor suppressor protein p53 and WISP-1 signaling pathways. WISP-1 acts to block cell death at a late stage in the p53-mediated apoptosis pathway. PMID- 11782445 TI - A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre-mRNP to stimulate 3'-end processing. AB - The stem-loop binding protein (SLBP) is the posttranscriptional regulator of histone mRNA in metazoan cells. SLBP binds histone pre-mRNAs and facilitates 3' end processing by promoting stable association of U7 snRNP with the pre-mRNA. To identify other factors involved in histone pre-mRNA processing, we used a modified yeast two-hybrid assay in which SLBP and its RNA target were coexpressed as bait. A novel zinc finger protein, hZFP100, which interacts with the SLBP/RNA complex but not with free SLBP, was cloned. The interaction requires regions of SLBP that are important for histone pre-mRNA processing. Antibodies to hZFP100 precipitate U7 snRNA, and expression of hZFP100 in Xenopus oocytes stimulates processing of histone pre-mRNA, showing that hZFP100 is a component of the processing machinery. PMID- 11782446 TI - The KH-type RNA-binding protein PSI is required for Drosophila viability, male fertility, and cellular mRNA processing. AB - Direct interactions between RNA-binding proteins and snRNP particles modulate eukaryotic pre-mRNA processing patterns to control gene expression. Here, we report that the conserved U1 snRNP-interacting RNA-binding protein PSI is essential for Drosophila viability. A null PSI mutation is recessive lethal at the first-instar larval stage, and lethality is fully rescued by transgenes expressing the PSI protein. A mutant transgene that lacks the PSI-U1 snRNP interaction domain restores viability but shows courtship behavior abnormalities and meiosis defects during spermatogenesis, resulting in a complete male sterility phenotype. Using cDNA microarrays, we have identified specific target mRNAs with altered expression profiles in these mutant males. A subset of these transcripts is also found associated with PSI in endogenous immunopurified ribonucleoprotein complexes. One specific target, the hrp40/squid transcript, shows an altered pre-mRNA splicing pattern in PSI mutant testes. We conclude that a functional association between the PSI protein and the spliceosomal U1 snRNP particle is required for normal Drosophila development and for the processing of specific PSI-interacting cellular transcripts. These results also validate the use of cDNA microarrays to characterize in vivo RNA-processing defects and alternative pre-mRNA splicing patterns. PMID- 11782447 TI - Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae. AB - Budding yeast centromeres are comprised of approximately 125-bp DNA sequences that direct formation of the kinetochore, a specialized chromatin structure that mediates spindle attachment to chromosomes. We report here a novel role for the histone deposition complex chromatin assembly factor I (CAF-I) in building centromeric chromatin. The contribution of CAF-I to kinetochore function overlaps that of the Hir proteins, which have also been implicated in nucleosome formation and heterochromatic gene silencing. cacDelta hirDelta double mutant cells lacking both CAF-I and Hir proteins are delayed in anaphase entry in a spindle assembly checkpoint-dependent manner. Further, cacDelta and hirDelta deletions together cause increased rates of chromosome missegregation, genetic synergies with mutations in kinetochore protein genes, and alterations in centromeric chromatin structure. Finally, CAF-I subunits and Hir1 are enriched at centromeres, indicating that these proteins make a direct contribution to centromeric chromatin structures. PMID- 11782448 TI - Ctf3p, the Mis6 budding yeast homolog, interacts with Mcm22p and Mcm16p at the yeast outer kinetochore. AB - The budding yeast kinetochore is composed of an inner and outer protein complex, which binds to centromere (CEN) DNA and attaches to microtubules. We performed a genetic synthetic dosage lethality screen to identify novel kinetochore proteins in a collection of chromosome transmission fidelity mutants. Our screen identified several new kinetochore-related proteins including YLR381Wp/Ctf3p, which is a member of a conserved family of centromere-binding proteins. Ctf3p interacts with Mcm22p, Mcm16p, and the outer kinetochore protein Ctf19p. We used chromatin immunoprecipitation to demonstrate that Ctf3p, Mcm22p, and Mcm16p bind to CEN DNA in a Ctf19p-dependent manner. In addition, Ctf3p, Mcm22p, and Mcm16p have a localization pattern similar to other kinetochore proteins. The fission yeast Ctf3p homolog, Mis6, is required for loading of a CENP-A centromere specific histone, Cnp1, onto centromere DNA. We find however that Ctf3p is not required for loading of the budding yeast CENP-A homolog, Cse4p, onto CEN DNA. In contrast, Ctf3p and Ctf19p fail to bind properly to the centromere in a cse4-1 mutant strain. We conclude that the requirements for CENP-A loading onto centromere DNA differ in fission versus budding yeast. PMID- 11782449 TI - Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. AB - Sonic hedgehog (Shh) is a secreted signaling molecule for tissue patterning and stem cell specification in vertebrate embryos. Shh mediates both long-range and short-range signaling responses in embryonic tissues through the activation and repression of target genes by its Gli transcription factor effectors. Despite the well-established functions of Shh signaling in development and human disease, developmental target genes of Gli regulation are virtually unknown. In this study, we investigate the role of Shh signaling in the control of Myf5, a skeletal muscle regulatory gene for specification of muscle stem cells in vertebrate embryos. In previous genetic studies, we showed that Shh is required for Myf5 expression in the specification of dorsal somite, epaxial muscle progenitors. However, these studies did not distinguish whether Myf5 is a direct target of Gli regulation through long-range Shh signaling, or alternatively, whether Myf5 regulation is a secondary response to Shh signaling. To address this question, we have used transgenic analysis with lacZ reporter genes to characterize an Myf5 transcription enhancer that controls the activation of Myf5 expression in the somite epaxial muscle progenitors in mouse embryos. This Myf5 epaxial somite (ES) enhancer is Shh-dependent, as shown by its complete inactivity in somites of homozygous Shh mutant embryos, and by its reduced activity in heterozygous Shh mutant embryos. Furthermore, Shh and downstream Shh signal transducers specifically induce ES enhancer/luciferase reporters in Shh responsive 3T3 cells. A Gli-binding site located within the ES enhancer is required for enhancer activation by Shh signaling in transfected 3T3 cells and in epaxial somite progenitors in transgenic embryos. These findings establish that Myf5 is a direct target of long-range Shh signaling through positive regulation by Gli transcription factors, providing evidence that Shh signaling has a direct inductive function in cell lineage specification. PMID- 11782451 TI - A. thaliana TRANSPARENT TESTA 1 is involved in seed coat development and defines the WIP subfamily of plant zinc finger proteins. AB - Seeds of the Arabidopsis thaliana transparent testa 1 mutant (tt1) appear yellow, due to the lack of condensed tannin pigments in the seed coat. The TT1 gene was isolated by reverse genetics using an En-1 transposon mutagenized A. thaliana population. TT1 gene expression was detected in developing ovules and young seeds only, and the gene was shown to encode a nuclear protein. Mutant seeds displayed altered morphology of the seed endothelium in which brown tannin pigments accumulate in wild-type plants, indicating that TT1 is involved in the differentiation of this cell layer. When overexpressed in transgenic A. thaliana plants, TT1 caused aberrant development and organ morphology. The protein contains a novel combination of two TFIIIA-type zinc finger motifs. Closely related motifs were detected in a number of putative proteins deduced from plant genomic and EST sequences. The new protein domain containing this type of zinc finger motifs was designated WIP, according to three strictly conserved amino acid residues. Our data indicate the existence of a small gene family in A. thaliana which is defined by the occurrence of the WIP domain. WIP genes may play important roles in regulating developmental processes, including the control of endothelium differentiation. PMID- 11782450 TI - An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors. AB - The ETS transcription factors perform distinct biological functions despite conserving a highly similar DNA-binding domain. One distinguishing property of a subset of ETS proteins is a conserved region of 80 amino acids termed the Pointed (PNT) domain. Using enzyme kinetics we determined that the Ets-1 PNT domain contains an ERK2 docking site. The docking site enhances the efficiency of phosphorylation of a mitogen-activated protein kinase (MAPK) site N-terminal to the PNT domain. The site enhances ERK2 binding rather than catalysis. Three hydrophobic residues are involved in docking, and the previously determined NMR structure indicates that these residues are clustered on the surface of the Ets-1 PNT domain. The docking site function is conserved in the PNT domain of the highly related Ets-2 but not in the ets family member GABPalpha. Ablation of the docking site in Ets-1 and Ets-2 prevented Ras pathway-mediated enhancement of the transactivation function of these proteins. This study provides structural insight into the function of a MAPK docking site and describes a unique activity for the PNT domain among a subset of ets family members. PMID- 11782452 TI - Antiplasmin activity of a peptide that binds to the receptor-binding site of angiogenin. AB - It has been suggested that angiogenin binds to an actin-like molecule present on the surface of endothelial cells. Actin inhibits plasmin activity, but the angiogenin-actin complex is not active. In this report, we found that plasmin inhibits the interaction between angiogenin and actin suggesting a possibility that both angiogenin and plasmin may bind to a similar site on actin. Here we report that chANG, an antiangiogenin peptide that binds to the actin-binding site of angiogenin, inhibits the proteolytic activity of plasmin without any apparent effect on the activities of plasminogen activators and matrix metalloproteases. Its antiplasmin activity is comparable with that of actin. chANG inhibits plasmin activity via its binding to plasmin kringle domains while scrambled chANG does not bind to plasmin. chANG also inhibits the invasion of angiogenin-secreting human fibrosarcoma and colorectal carcinoma cells without effecting migration. Furthermore, chANG blocks angiogenesis induced by fibrosarcoma cells and metastasis of colorectal carcinoma cells to the liver. Therefore, the 11-amino acid peptide chANG has both antiangiogenin and antiplasmin activity, and could be useful in the development of anticancer agents. PMID- 11782453 TI - Kinetic and structural characterization of adsorption-induced unfolding of bovine alpha -lactalbumin. AB - Conformational changes of bovine alpha-lactalbumin induced by adsorption on a hydrophobic interface are studied by fluorescence and circular dichroism spectroscopy. Adsorption of bovine alpha-lactalbumin on hydrophobic polystyrene nanospheres induces a non-native state of the protein, which is characterized by preserved secondary structure, lost tertiary structure, and release of calcium. This partially denatured state therefore resembles a molten globule state, which is an intermediate in the folding of bovine alpha-lactalbumin. Stopped-flow fluorescence spectroscopy reveals two kinetic phases during adsorption with rate constants k(1) approximately 50 s(-1) and k(2) approximately 8 s(-1). The rate of partial unfolding is remarkably fast and even faster than unfolding induced by the addition of 5.4 m guanidinium hydrochloride to native alpha-lactalbumin. The large unfolding rates exclude the possibility that unfolding of bovine alpha lactalbumin to the intermediate state occurs before adsorption takes place. Stopped-flow fluorescence anisotropy experiments show that adsorption of bovine alpha-lactalbumin on polystyrene nanospheres occurs within the dead time (15 ms) of the experiment. This shows that the kinetic processes as determined by stopped flow fluorescence spectroscopy are not affected by diffusion or association processes but are solely caused by unfolding of bovine alpha-lactalbumin induced by adsorption on the polystyrene surface. A scheme is presented that incorporates the results obtained and describes the adsorption of bovine alpha-lactalbumin. PMID- 11782454 TI - Molecular dynamics characterization of the C2 domain of protein kinase Cbeta. AB - Protein kinase C (PKC) isozymes comprise a family of related enzymes that play a central role in many intracellular eukaryotic signaling events. Isozyme specificity is mediated by association of each PKC isozyme with specific anchoring proteins, termed RACKs. The C2 domain of betaPKC contains at least part of the RACK-binding sites. Because the C2 domain contains also a RACK-like sequence (termed pseudo-RACK), it was proposed that this pseudo-RACK site mediates intramolecular interaction with one of the RACK-binding sites in the C2 domain itself, stabilizing the inactive conformation of betaPKC. BetaPKC depends on calcium for its activation, and the C2 domain contains the calcium-binding sites. The x-ray structure of the C2 domain of betaPKC shows that three Ca(2+) ions can be coordinated by two opposing loops at one end of the domain. Starting from this x-ray structure, we have performed molecular dynamics (MD) calculations on the C2 domain of betaPKC bound to three Ca(2+) ions, to two Ca(2+) ions, and in the Ca(2+)-free state, in order to analyze the effect of calcium on the RACK binding sites and the pseudo-RACK sites, as well as on the loops that constitute the binding site for the Ca(2+) ions. The results show that calcium stabilizes the beta-sandwich structure of the C2 domain and thus affects two of the three RACK-binding sites within the C2 domain. Also, the interactions between the third RACK-binding site and the pseudo-RACK site are not notably modified by the removal of Ca(2+) ions. On that basis, we predict that the pseudo-RACK site within the C2 domain masks a RACK-binding site in another domain of betaPKC, possibly the V5 domain. Finally, the MD modeling shows that two Ca(2+) ions are able to interact with two molecules of O-phospho-l-serine. These data suggest that Ca(2+) ions may be directly involved in PKC binding to phosphatidylserine, an acidic lipid located exclusively on the cytoplasmic face of membranes, that is required for PKC activation. PMID- 11782456 TI - Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers. AB - Integrin binding to extracellular matrix proteins induces formation of signaling complexes at focal adhesions. Zyxin co-localizes with integrins at sites of cell substratum adhesion and is postulated to serve as a docking site for the assembly of multimeric protein complexes involved in regulating cell motility. Recently, we identified a new member of the zyxin family called TRIP6. TRIP6 is localized at focal adhesions and overexpression of TRIP6 slows cell migration. In an effort to define the molecular mechanism by which TRIP6 affects cell migration, the yeast two-hybrid assay was employed to identify proteins that directly bind to TRIP6. This assay revealed that both TRIP6 and zyxin interact with CasL/HEF1, a member of the Cas family. This association is mediated by the LIM region of the zyxin family members and the SH2 domain-binding region of CasL/HEF1. Furthermore, the association between p130(Cas) and the two zyxin family members was demonstrated to occur in vivo by co-immunoprecipitation. Zyxin and Cas family members may cooperate to regulate cell motility. PMID- 11782455 TI - Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments. AB - MEKK1, a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase, generates anti-apoptotic signaling as a full-length protein but induces apoptosis when cleaved by caspases. Here, we show that caspase-dependent cleavage of MEKK1 relocalizes the protease-generated 91-kDa kinase fragment from a particulate fraction to a soluble cytoplasmic fraction. Relocalization of MEKK1 catalytic activity is necessary for the pro-apoptotic function of MEKK1. The addition of a membrane-targeting signal to the 91-kDa fragment inhibits caspase activation and the induction of apoptosis but does not change the activation of JNK, ERK, NFkappaB, or p300. These results identify the caspase cleavage of MEKK1 as a dynamic regulatory mechanism that alters the subcellular distribution of MEKK1, changing its function to pro-apoptotic signaling, which does not depend on the currently described MEKK1 effectors. PMID- 11782457 TI - Isolation and characterization of the two major intracellular Glut4 storage compartments. AB - In rat adipose cells, intracellular Glut4 resides in two distinct vesicular populations one of which contains cellugyrin whereas another lacks this protein (Kupriyanova, T. A., and Kandror, K. V. (2000) J. Biol. Chem. 275, 36263--36268). Cell surface biotinylated MPR and (125)I-labeled transferrin are accumulated in cellugyrin-positive vesicles and to a lesser extent in cellugyrin-negative vesicles. An average cellugyrin-positive vesicle carries not more than one molecule of either Glut4, insulin-responsive aminopeptidase (IRAP), or transferrin receptor (TfR), whereas cellugyrin-negative vesicles contain five to six molecules of Glut4, more than 10 molecules of IRAP, and still one molecule of TfR per vesicle. Cellugyrin-negative vesicles are translocated to the cell surface after insulin stimulation, whereas cellugyrin-positive vesicles maintain intracellular localization both in the absence and in the presence of insulin and, therefore, may be involved in interendosomal protein transport. Both cellugyrin-positive and cellugyrin-negative vesicles are present in extracts of non-homogenized cells and therefore may represent the major form of Glut4 storage in vivo. PMID- 11782458 TI - Conservation of the phosphate-sensitive elements in the arrestin family of proteins. AB - Arrestins play a key role in the homologous desensitization of G protein-coupled receptors (GPCRs). These cytosolic proteins selectively bind to the agonist activated and GPCR kinase-phosphorylated forms of the GPCR, precluding its further interaction with the G protein. Certain mutations in visual arrestin yield "constitutively active" proteins that bind with high affinity to the light activated form of rhodopsin without requiring phosphorylation. The crystal structure of visual arrestin shows that these activating mutations perturb two groups of intramolecular interactions that keep arrestin in its basal (inactive) state. Here we introduced homologous mutations into arrestin2 and arrestin3 and found that the resulting mutants bind to the beta(2)-adrenoreceptor in vitro in a phosphorylation-independent fashion. The same mutants effectively desensitize both the beta(2)-adrenergic and delta-opioid receptors in the absence of receptor phosphorylation in Xenopus oocytes. Moreover, the arrestin mutants also desensitize the truncated delta-opioid receptor from which the C terminus, containing critical phosphorylation sites, has been removed. Conservation of the phosphate-sensitive hot spots in non-visual arrestins suggests that the overall fold is similar to that of visual arrestin and that the mechanisms whereby receptor-attached phosphates drive arrestin transition into the active binding competent state are conserved throughout the arrestin family of proteins. PMID- 11782459 TI - Dissecting the chemistry of nicotinic receptor-ligand interactions with infrared difference spectroscopy. AB - The physical interactions that occur between the nicotinic acetylcholine receptor from Torpedo and the agonists carbamylcholine and tetramethylamine have been studied using both conventional infrared difference spectroscopy and a novel double-ligand difference technique. The latter was developed to isolate vibrational bands from residues in a membrane receptor that interact with individual functional groups on a small molecule ligand. The binding of either agonist leads to an increase in vibrational intensity at frequencies centered near 1663, 1655, 1547, 1430, and 1059 cm(-1) indicating that both induce a conformational change from the resting to the desensitized state. Vibrational shifts near 1580, 1516, 1455, 1334, and between 1300 and 1400 cm(-1) are assigned to structural perturbations of tyrosine and possibly both tryptophan and charged carboxylic acid residues upon the formation of receptor-quaternary amine interactions, with the relatively intense feature near 1516 cm(-1) indicating a key role for tyrosine. Other vibrational bands suggest the involvement of additional side chains in agonist binding. Two side-chain vibrational shifts from 1668 and 1605 cm(-1) to 1690 and 1620 cm(-1), respectively, could reflect the formation of a hydrogen bond between the ester carbonyl of carbamylcholine and an arginine residue. The results demonstrate the potential of the double-ligand difference technique for dissecting the chemistry of membrane receptor-ligand interactions and provide new insight into the nature of nicotinic receptor agonist interactions. PMID- 11782460 TI - Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival. AB - Huntington's disease (HD) is one of eight established triplet repeat neurodegenerative disorders, which are collectively caused by the genetic expansion of polyglutamine repeats. While the mechanism(s) by which polyglutamine expansion causes neurodegeneration in each of these disorders is being intensely investigated, the underlying cause of polyglutamine toxicity has not been fully elucidated. A number of studies have focused on the potential role of protein aggregation and disruption of the proteasome proteolytic pathway in polyglutamine mediated neurodegeneration. However, at present it is not clear whether polyglutamine-mediated protein aggregation is sufficient to induce cell death, nor has it been clearly determined whether proteasome inhibition precedes, coincides, or occurs as the result of the formation of polyglutamine-associated protein aggregation. To address these important components of polyglutamine toxicity, in the present study we utilized neural SH-SY5Y cells stably transfected with polyglutamine-green fluorescent protein constructs to examine the effects of polyglutamine expansion on protein aggregation, proteasome activity, and neural cell survival. Data from the present study demonstrate that polyglutamine expansion does not dramatically impair proteasome activity or elevate protein aggregate formation under basal conditions, but does significantly impair the ability of the proteasome to respond to stress, and increases stress-induced protein aggregation following stress, all in the absence of neural cell death. PMID- 11782461 TI - Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals. AB - To investigate the molecular mechanisms of gangliosides for the regulation of cell proliferation, Swiss 3T3 cells were transfected with GM2/GD2 synthase and GM1 synthase cDNAs, resulting in the establishment of GM1-expressing (GM1(+)) lines. Compared with the vector control (GM1(-)) cell lines, GM1(+) cells exhibited reduced cell proliferation by stimulation with platelet-derived growth factor (PDGF). In accordance with the reduced cell growth, GM1(+) cells showed earlier decreases in the phosphorylation levels of PDGF receptor and less activation of MAP kinases than GM1(-) cells. To analyze the effects of GM1 expression on the PDGF/PDGF receptor (PDGFR) signals, the glycolipid-enriched microdomain (GEM) was isolated and the following results were obtained. (i) PDGFR predominantly distributed in the non-GEM fraction in GM1(+) cells, while it was present in both GEM and non-GEM fractions in GM1(-) cells. (ii) Activation of PDGFR as detected by anti-phosphotyrosine antibody occurred almost in parallel with existing amounts of PDGFR in each fraction. (iii) GM1 binds with PDGFR in GEM fractions. These findings suggested that GM1 regulates signals via PDGF/PDGFR by controlling the distribution of PDGFR in- and outside of GEM, and also interacting with PDGFR in the GEM fraction as a functional constituent of the microdomain. PMID- 11782462 TI - Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium-derived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5. AB - We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. Here we report that K5 down-regulates an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF) and up-regulates an angiogenic inhibitor, pigment epithelium-derived factor (PEDF) in a dose-dependent manner in vascular cells and in the retina. The regulation of VEGF and PEDF by K5 in the retina correlates with its anti-angiogenic effect in a rat model of ischemia-induced retinopathy. Retinal RNA levels of VEGF and PEDF are also changed by K5. K5 inhibits the p42/p44 MAP kinase activation and nuclear translocation of hypoxia-inducible factor-1alpha, which may be responsible for the down-regulation of VEGF. Down-regulation of endogenous angiogenic stimulators and up-regulation of endogenous angiogenic inhibitors, thus leading toward restoration of the balance in angiogenic control, may represent a mechanism for the anti-angiogenic activity of K5. PMID- 11782463 TI - Sickle hemoglobin polymer stability probed by triple and quadruple mutant hybrids. AB - As part of an effort to understand the interactions in HbS polymerization, we have produced and studied a recombinant triple mutant, D6A(alpha)/D75Y(alpha)/E121R(beta), and a quadruple mutant comprising the preceding mutation plus the natural genetic mutation of sickle hemoglobin, E6V(beta). These recombinant hemoglobins expressed in yeast were extensively characterized, and their structure and oxygen binding cooperativity were found to be normal. Their tetramer-dimer dissociation constants were within a factor of 2 of HbA and HbS. Polymerization of these mutants mixed with HbS was investigated by a micromethod based on volume exclusion by dextran. The elevated solubility of mixtures of HbS with HbA and HbF in dextran could be accurately predicted without any variable parameters. Relative to HbS, the copolymerization probability of the quadruple mutant/HbS hybrid was found to be 6.2, and the copolymerization probability for the triple mutant/HbS hybrid was 0.52. The pure quadruple mutant had a solubility slightly above that of its hybrid with HbS. One way to explain these results is to require significant cis-trans differences in the polymer and that HbA assemble above 42.5 g/dl. A second way to explain these data is by the modification of motional freedom, thereby changing vibrational entropy in the polymer. PMID- 11782464 TI - Association of chemokine-mediated block to HIV entry with coreceptor internalization. AB - Chemokines inhibit entry of HIV into CD4(+) T cells more effectively than into macrophages or transfected adherent cells. Here, we tested whether chemokine receptor internalization could account for cell type differences in the effectiveness of chemokines. Infection of CEM T cells expressing stably transduced wild-type CCR5 was much more readily inhibited by chemokine than were transduced HOS cells. This response correlated with the efficiency of CCR5 internalization. A mutated CCR5, termed M7-CCR5, in which the Ser/Thr phosphorylation sites in the cytoplasmic tail were changed to Ala, did not internalize in response to MIP-1alpha. M7-CCR5 was expressed at slightly higher levels than wild-type on stably transduced cell lines and was somewhat more potent as an HIV-1 coreceptor. The mutated receptor mobilized intracellular Ca(2+) in response to chemokine to a level 4-fold higher than did the wild type CCR5. Unexpectedly, the receptor was desensitized as efficiently as wild type, suggesting that desensitization does not require cytoplasmic tail phosphorylation. Entry of R5 HIV-1 reporter virus into cells stably expressing M7 CCR5 was largely resistant to blocking by MIP-1alpha. As much as 80% of entry inhibition was attributed to receptor internalization. Aminooxypentane (AOP)-MIP 1alpha was able to induce a low level of M7-CCR5 internalization in HOS and to weakly inhibit HIV-1 entry. Introduction of dominant negative dynamin into HOS cells reduced the ability of chemokine to inhibit infection. The inefficiency of internalization of chemokine receptors in some cell types could allow virus to replicate in vivo in the presence of endogenous chemokine. Last, M7-CCR5 is a useful tool for discriminating coreceptor internalization from binding site masking in the evaluation of small molecule inhibitors of HIV-1 entry. PMID- 11782465 TI - ERK activation by G-protein-coupled receptors in mouse brain is receptor identity specific. AB - In transfected cells and non-neuronal tissues many G-protein-coupled receptors activate p44/42 MAP kinase (ERK), a kinase involved in both hippocampal synaptic plasticity and learning and memory. However, it is not clear to what degree these receptors couple to ERK in brain. G(s)-coupled beta-adrenergic receptor activation of ERK in neurons is critical in the regulation of synaptic plasticity in area CA1 of the hippocampus. In addition, alpha(1)- and alpha(2)-adrenergic receptors, present in CA1, could potentially activate ERK. We find that, like the beta-adrenergic receptor, the G(q)-coupled alpha(1)AR activates ERK in adult mouse CA1. However, activation of the G(i/o)-coupled alpha(2)AR does not activate ERK, nor does activation of a homologous G(i/o)-coupled receptor enriched in adult mouse CA1, the 5HT(1A) receptor. In contrast, the nonhomologous G(i/o) coupled gamma-aminobutyric acid type B receptor does activate ERK in adult mouse CA1. Surprisingly, activation of alpha(2)ARs in CA1 from immature animals where basal phospho-ERK is low induces ERK phosphorylation. These data suggest that although most G-protein-coupled receptor subtypes activate ERK in non-neuronal cells, the coupling of G(i/o) to ERK is tightly regulated in brain. PMID- 11782466 TI - Affinity alkylation of the Trp-B4 residue of the beta -subunit of the glutaryl 7 aminocephalosporanic acid acylase of Pseudomonas sp. 130. AB - Glutaryl 7-aminocephalosporanic acid acylase of Pseudomonas sp. 130 (C130) was irreversibly inhibited in a time-dependent manner by two substrate analogs bearing side chains of variable length, namely 7beta-bromoacetyl aminocephalosporanic acid (BA-7-ACA) and 7beta-3-bromopropionyl aminocephalosporanic acid (BP-7-ACA). The inhibition of the enzyme with BA-7-ACA was attributable to reaction with a single amino acid residue within the beta subunit proven by comparative matrix assisted laser desorption/ionization-time of flight mass spectrometry. Further mass spectrometric analysis demonstrated that the fourth tryptophan residue of the beta-subunit, Trp-B4, was alkylated by BA-7 ACA. By (1)H-(13)C HSQC spectroscopy of C130 labeled by BA-2-(13)C-7-ACA, it was shown that tryptophan residue(s) in the enzyme was alkylated, forming a carbon carbon bond. Replacing Trp-B4 with other amino acid residues caused increases in K(m), decreases in k(cat), and instability of enzyme activity. None of the mutant enzymes except W-B4Y could be affinity-alkylated, but all were competitively inhibited by BA-7-ACA. Kinetic studies revealed that both BA-7-ACA and BP-7-ACA could specifically alkylate Trp-B4 of C130 as well as Tyr-B4 of the mutant W-B4Y. Because these alkylations were energy-requiring under physiological conditions, it is likely that the affinity labeling reactions were catalyzed by the C130 enzyme itself. The Trp-B4 residue is located in the middle of a characteristic alphabetabetaalpha sandwich structure. Therefore, a large conformational alteration during inhibitor binding and transition state formation is likely and suggests that a major conformational change is induced by substrate binding during the course of catalysis. PMID- 11782467 TI - p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300. AB - The tumor suppressor p53 recruits the cellular coactivator CBP/p300 to mediate the transcriptional activation of target genes. In this study, we identify a novel p53-interacting region in CBP/p300, which we call CR2, located near the carboxyl terminus. The 95-amino acid CR2 region (amino acids 2055--2150) is located adjacent to the C/H3 domain and corresponds precisely with the minimal steroid receptor coactivator 1 (SRC1)-interacting domain of CBP (also called IBiD). We show that the region of p53 that participates in the CR2 interaction resides within the first 107 amino acids of the protein. p53 binds strongly to the CR2 domain of both CBP and the highly homologous coactivator p300. Importantly, an in-frame deletion of CR2 within the full-length p300 protein strongly compromises p300-mediated p53 transcriptional activation from a chromatin template in vitro. The identification of the p53-interacting CR2 domain in CBP/p300 prompted us to ask if the human T-cell leukemia virus (HTLV-I) Tax protein, which also interacts with CR2, competes with p53 for binding to this domain. We show that p53 and Tax exhibit mutually exclusive binding to the CR2 region, possibly contributing to the previously reported Tax repression of p53 function. Together, these studies identify and molecularly characterize a new p53 binding site on CBP/p300 that participates in coactivator-mediated p53 transcription function. The identity of the p53.CR2 interaction indicates that at least three distinct sites on CBP/p300 may participate in mediating p53 transactivation. PMID- 11782468 TI - Methylseleninate is a substrate rather than an inhibitor of mammalian thioredoxin reductase. Implications for the antitumor effects of selenium. AB - Biochemical and clinical evidence indicates that monomethylated selenium compounds are crucial for the tumor preventive effects of the trace element selenium and that methylselenol (CH(3)SeH) is a key metabolite. As suggested by Ganther (Ganther, H. E. (1999) Carcinogenesis 20, 1657-1666), methylselenol and its precursor methylseleninate might exert their effects by inhibition of the selenoenzyme thioredoxin reductase via the irreversible formation of a diselenide bridge. Here we report that methylseleninate does not act as an inhibitor of mammalian thioredoxin reductase but is in fact an excellent substrate (K(m) of 18 microm, k(cat) of 23 s(-1)), which is reduced by the enzyme according to the equation 2 NADPH + 2 H(+) + CH(3)SeO(2)H --> 2 NADP(+) + 2 H(2)O + CH(3)SeH. The selenium-containing product of this reaction was identified by mass spectrometry. Nascent methylselenol was found to efficiently reduce both H(2)O(2) and glutathione disulfide. The implications of these findings for the antitumor activity of selenium are discussed. Methylseleninate was a poor substrate not only for human glutathione reductase but also for the non-selenium thioredoxin reductases enzymes from Drosophila melanogaster and Plasmodium falciparum. This suggests that the catalytic selenocysteine residue of mammalian thioredoxin reductase is essential for methylseleninate reduction. PMID- 11782469 TI - Insulin stimulates phosphorylation of the beta 2-adrenergic receptor by the insulin receptor, creating a potent feedback inhibitor of its tyrosine kinase. AB - Insulin counterregulates catecholamine action at several levels, primarily in liver, fat, and adipose tissue. Herein we observe that expression of increased levels of beta(2)-adrenergic receptor increasingly inhibits insulin-stimulated phosphorylation of its primary downstream substrates (IRS-1,2). In Chinese hamster ovary cells, the insulin receptor phosphorylates dominantly Tyr(364) in the C-terminal cytoplasmic domain of the beta-receptor. A Y364A mutant form of the beta(2)-adrenergic, in contrast, loses it ability to inhibit insulin stimulated phosphorylation of IRS-1,2. Upon phosphorylation, the C-terminal cytoplasmic domain of the beta(2)-adrenergic receptor demonstrates a potent inhibitory feedback action that can block both insulin-stimulated autophosphorylation of the insulin receptor and phosphorylation of IRS-1,2 in NIH mouse 3T3-L1 adipocyte membranes. Studies in vitro with purified insulin receptor and the C-terminal cytoplasmic domain of the beta(2)-adrenergic receptor demonstrate that the tyrosine-phosphorylated beta-receptor domain is a potent counterregulatory inhibitor of the insulin receptor tyrosine kinase. PMID- 11782470 TI - Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins. AB - Expression levels of Gb3/CD77 synthase together with Gb3/CD77 antigen were analyzed using human hematopoietic tumor cell lines and normal cells. Among about 40 kinds of cells, Burkitt lymphoma cells showed the highest gene expression concomitant with the expression levels of Gb3/CD77. Unexpectedly, megakaryoblastic leukemia lines also expressed fairly high levels of mRNA of Gb3/CD77 synthase and its product. A megakaryoblastic leukemia line, MEG-01 was sensitive to verotoxins from Escherichia coli O157 and apoptosis was induced via the caspase pathway. We also demonstrated that the cell surface Gb3/CD77 expression was reduced on differentiated MEG-01 although the mRNA level of the alpha1,4Gal-T gene increased. In this case, the localization of Gb3/CD77 was changed from the cell surface to the cytoplasm as stained with a granular pattern, co-localizing with platelet GPIIb-IIIa, indicating that some of them were platelet precursors. Small particles outside of cells also showed similar staining patterns. These results agreed with the previous report that platelets produced in mature megakaryoblasts abundantly contained Gb3/CD77 antigen. Here, we propose the possibility that verotoxins bind immature megakaryoblasts and induce their apoptosis, leading to the arrest of platelet generation in the bone marrow. This may be one of the causes of thrombocytopenia in patients with hemolytic uremic syndrome. PMID- 11782471 TI - Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca2+ binding domain. AB - Chondrocytes from pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) patients display an enlarged rough endoplasmic reticulum that accumulates extracellular matrix proteins, including cartilage oligomeric matrix protein (COMP). Mutations that cause PSACH and EDM1 are restricted to a 27-kDa Ca(2+) binding domain (type 3 repeat). This domain has 13 Ca(2+)-binding loops with a consensus sequence that conforms to Ca(2+)-binding loops found in EF hands. Most disease-causing mutations are found in the 11-kDa C-terminal region of this domain. We expressed recombinant native and mutant forms of the type 3 repeat domain (T3) and its 11-kDa C-terminal region (T3-Cterm). T3 and T3-Cterm bind approximately 13 and 8 mol of Ca(2+)/mol of protein, respectively. CD, one dimensional proton, and two-dimensional (1)H-(15)N HSQC spectra of Ca(2+)-bound T3-Cterm indicate a distinct conformation that has little helical secondary structure, despite the presence of 13 EF hand Ca(2+)-binding loops. This conformation is also formed within the context of the intact T3. 19 cross-peaks found between 9.0 and 11.4 ppm are consistent with the presence of strong hydrogen bonding patterns, such as those in beta-sheets. Removal of Ca(2+) leads to an apparent loss of structure as evidenced by decreased dispersion and loss of all down field resonances. Deletion of Asp-470 (a mutation found in 22% of all PSACH and EDM1 patients) decreased the Ca(2+)-binding capacity of both T3 and T3 Cterm by about 3 mol of Ca(2+)/mol of protein. Two-dimensional (1)H-(15)N HSQC spectra of mutated T3-Cterm showed little evidence of defined structure in the presence or absence of Ca(2+). The data demonstrate that Ca(2+) is required to nucleate folding and to maintain defined structure. Mutation results in a partial loss of Ca(2+)-binding capacity and prevents Ca(2+)-dependent folding. Persistence of an unstructured state of the mutated Ca(2+) binding domain in COMP is the structural basis for retention of COMP in the rough endoplasmic reticulum of differentiated PSACH and EDM1 chondrocytes. PMID- 11782472 TI - TGTCACA motif is a novel cis-regulatory enhancer element involved in fruit specific expression of the cucumisin gene. AB - Cucumisin, a subtilisin-like serine protease, is expressed at high levels in the fruit of melon (Cucumis melo L.) and accumulates in the juice. We investigated roles of the promoter regions and DNA-protein interactions in fruit-specific expression of the cucumisin gene. In transient expression analysis, a chimeric gene construct containing a 1.2-kb cucumisin promoter fused to a beta glucuronidase (GUS) reporter gene was expressed in fruit tissues at high levels, but the promoter activities in leaves and stems were very low. Deletion analysis indicated that a positive regulatory region is located between nucleotides -234 and -214 relative to the transcriptional initiation site. Gain-of-function experiments revealed that this 20-bp sequence conferred fruit specificity and contained a regulatory enhancer. Gel mobility shift experiments demonstrated the presence of fruit nuclear factors that interact with the cucumisin promoter. A typical G-box (GACACGTGTC) present in the 20-bp sequence did not bind fruit protein, but two possible cis-elements, an I-box-like sequence (AGATATGATAAAA) and an odd base palindromic TGTCACA motif, were identified in the promoter region between positions -254 and -215. The I-box-like sequence bound more tightly to fruit nuclear protein than the TGTCACA motif. The I-box-like sequence functions as a negative regulatory element, and the TGTCACA motif is a novel enhancer element necessary for fruit-specific expression of the cucumisin gene. Specific nucleotides responsible for the binding of fruit nuclear protein in these two elements were also determined. PMID- 11782473 TI - Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes. AB - Peroxisome proliferator-activated receptor-alpha (PPARalpha)activators, fish oil feeding, or fibrate administration up-regulated mitochondrial uncoupling protein (UCP2) mRNA expression in mouse liver by 5-9-fold, whereas tumor necrosis factor alpha (TNFalpha) also up-regulated UCP2 in liver. In this study, the mechanisms for PPARalpha activators-induced up-regulation of UCP2 mRNA, related to TNFalpha and reactive oxygen species (ROS), were investigated. PPARalpha activators induced UCP2 up-regulation in mouse/rat liver tissues was due to their increases in hepatocytes but not in non-parenchymal cells. Addition of PPARalpha activators, WY14,643 or fenofibrate, to cultured hepatocytes up-regulated UCP2 mRNA by 5-10-fold. PPARalpha activators-induced up-regulation of UCP2 mRNA was not due to increased mRNA stability and required cycloheximide-sensitive short term turnover protein(s). However, expression of PPARalpha/retinoid X receptor alpha and PGC-1 was not rate-limiting for WY14,643-induced UCP2 up-regulation. In primary hepatocytes, an exogenous oxidant, tert-butyl-hydroperoxide (TBHP), which increased ROS production, up-regulated UCP2 mRNA, whereas WY14,643 treatment did not produce detectable ROS under the condition that fibrate markedly up-regulated UCP2. In in vivo studies, PPARalpha activators moderately up-regulated TNFalpha mRNA expression in mouse liver. An anti-oxidant pyrrolidine dithiocarbamate ammonium salt injection completely prevented their TNFalpha mRNA increases but did not prevent most of their UCP2 mRNA increases. These data indicate that PPARalpha activators up-regulate UCP2 expression in hepatocytes through unknown proteins by increased transcription, and neither ROS nor TNFalpha production are the major causes for PPARalpha activators-induced UCP2 up-regulation. PMID- 11782474 TI - FOXC1 transcriptional regulation is mediated by N- and C-terminal activation domains and contains a phosphorylated transcriptional inhibitory domain. AB - Mutations in the FOXC1 gene result in Axenfeld-Rieger malformations of the anterior segment of the eye and lead to an increased susceptibility of glaucoma. To understand how the FOXC1 protein may function in contributing to these malformations, we identified functional regions in FOXC1 required for nuclear localization and transcriptional regulation. Two regions in the FOXC1 forkhead domain, one rich in basic amino acid residues, and a second, highly conserved among all FOX proteins, were necessary for nuclear localization of the FOXC1 protein. However, only the basic region was sufficient for nuclear localization. Two transcriptional activation domains were identified in the extreme N- and C terminal regions of FOXC1. A transcription inhibitory domain was located at the central region of the protein. This region was able to reduce the trans activation potential of the C-terminal activation domain, as well as the GAL4 activation domain. Lastly, we demonstrate that FOXC1 is a phosphoprotein, and a number of residues predicted to be phosphorylated were localized to the FOXC1 inhibitory domain. Removal of residues 215-366 resulted in a transcriptionally hyperactive FOXC1 protein, which displayed a reduced level of phosphorylation. These results indicate that FOXC1 is under complex regulatory control with multiple functional domains modulating FOXC1 transcriptional regulation. PMID- 11782475 TI - Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs. AB - Tristetraprolin (TTP), the prototype of a small family of CCCH tandem zinc finger (TZF) domain proteins, is a physiological stimulator of instability of the mRNAs encoding tumor necrosis factor-alpha and granulocyte/macrophage colony stimulating factor in certain cell types. TTP stimulates mRNA turnover after binding to class II AU-rich elements (AREs) within the 3'-untranslated regions of both mRNAs. In turn, this binding is dependent upon the key CCCH residues in the TZF domain. To evaluate other primary sequence requirements for ARE binding in this novel mRNA-binding domain, we mutated many of the conserved residues within the TZF domain of human TTP and evaluated the effects of these mutations on RNA binding in a cell-free system and TTP-induced mRNA instability in cell transfection experiments. These mutations revealed a number of conserved amino acids that were required for binding and begin to define the primary protein sequence requirements for this novel mRNA-binding motif. Unexpectedly, all of the point mutations that prevented TTP binding to RNA also caused an increase in steady-state levels of ARE-containing mRNAs in cell transfection experiments. Actinomycin D experiments suggested that this effect was due to inhibition of mRNA turnover. Although expression of the mutant form of TTP could also inhibit the destruction of tumor necrosis factor-alpha mRNA by wild-type TTP, the primary mechanism did not involve heterodimerization with wild-type TTP because the 293 cells used in these studies express no detectable endogenous TTP. These data suggest that TTP may act, at least in part, by physically interacting with an enzyme activity or protein complex and functionally stimulating its ability to deadenylate class II ARE-containing mRNAs. PMID- 11782476 TI - Food deprivation-induced expression of minoxidil sulfotransferase in the hypothalamus uncovered by microarray analysis. AB - We used oligonucleotide microarrays to analyze comprehensively hypothalamic gene expression changes that correlate with energy homeostasis. We compared the hypothalamic gene expression profiles of freely fed and 48-h fasted rats using 26,379 oligonucleotide probe sets. Expression of 96 genes was up-regulated and expression of 73 genes was down-regulated in a statistically significant manner with fasting. The gene encoding the enzyme minoxidil sulfotransferase, an enzyme that catalyzes the transfer of sulfonate groups to biogenic amines and other substrates, was foremost among a set of genes whose mRNAs were uniformly detectable and displaying the greatest transcriptional changes with fasting. Northern blot analysis indicated that minoxidil sulfotransferase mRNA is up regulated in the fasted rat and mouse, ob/ob mouse, and fa/fa rat. Results of reverse transcription quantitative PCR indicated that minoxidil sulfotransferase mRNA is also up-regulated in the microdissected arcuate and paraventricular nuclei of the fasted rat. Several index genes known to be either up-regulated (neuropeptide Y) or down-regulated (amphetamine-regulated transcript and proopiomelanocortin) with fasting were also found to be present among our set of "differentially expressed" genes. This study identifies a novel gene induced by fasting and demonstrates the feasibility of using oligonucleotide microarrays for the study of complex neuronal processes. PMID- 11782477 TI - Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. AB - To evaluate possible fibrogenic effects of CYP2E1-dependent generation of reactive oxygen species, a model was developed using co-cultures of HepG2 cells, which do (E47 cells) or do not (C34 cells) express cytochrome P450 2E1 (CYP2E1) with stellate cells. There was an increase in intra- and extracellular H(2)O(2), lipid peroxidation, and collagen type I protein in stellate cells co-cultured with E47 cells compared with stellate cells alone or co-cultured with C34 cells. The increase in collagen was prevented by antioxidants and a CYP2E1 inhibitor. CYP3A4 did not mimic the stimulatory effects found with CYP2E1. Collagen mRNA levels remained unchanged, and pulse-chase analysis indicated similar half-lives of collagen I protein between both co-cultures. However, collagen protein synthesis was increased in E47 co-culture. Hepatocytes from pyrazole-treated rats (with high levels of CYP2E1) induced collagen protein in primary stellate cells, and antioxidants and CYP2E1 inhibitors blocked this effect. These results suggest that increased translation of collagen mRNA by CYP2E1-derived reactive oxygen species is responsible for the increase in collagen protein produced by the E47 co-culture. These co-culture models may be useful for understanding the impact of CYP2E1-derived ROS on stellate cell function and activation. PMID- 11782478 TI - Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors. AB - The basic helix-loop-helix/Per-Arnt-Sim homology (bHLH/PAS) protein family comprises a group of transcriptional regulators that often respond to a variety of developmental and environmental stimuli. Two murine members of this family, Single Minded 1 (SIM1) and Single Minded 2 (SIM2), are essential for postnatal survival but differ from other prototypical family members such as the dioxin receptor (DR) and hypoxia-inducible factors, in that they behave as transcriptional repressors in mammalian one-hybrid experiments and have yet to be ascribed a regulating signal. In cell lines engineered to stably express SIM1 and SIM2, we show that both are nuclear proteins that constitutively complex with the general bHLH/PAS partner factor, ARNT. We report that the murine SIM factors, in combination with ARNT, attenuate transcription from the hypoxia-inducible erythropoietin (EPO) enhancer during hypoxia. Such cross-talk between coexpressed bHLH/PAS factors can occur through competition for ARNT, which we find evident in SIM repression of DR-induced transcription from a xenobiotic response element reporter gene. However, SIM1/ARNT, but not SIM2/ARNT, can activate transcription from the EPO enhancer at normoxia, implying that the SIM proteins have the ability to bind hypoxia response elements and affect either activation or repression of transcription. This notion is supported by co-immunoprecipitation of EPO enhancer sequences with the SIM2 protein. SIM protein levels decrease with hypoxia treatment in our stable cell lines, although levels of the transcripts encoding SIM1 and SIM2 and the approximately 2-h half-lives of each protein are unchanged during hypoxia. Inhibition of protein synthesis, known to occur in cells during hypoxic stress in order to decrease ATP utilization, appears to account for the fall in SIM levels. Our data suggest the existence of a hypoxic switch mechanism in cells that coexpress hypoxia-inducible factor and SIM proteins, where up-regulation and activation of hypoxia-inducible factor-1alpha is concomitant with attenuation of SIM activities. PMID- 11782479 TI - The contribution of factor Xa to exosite-dependent substrate recognition by prothrombinase. AB - Kinetic studies support the concept that protein substrate recognition by the prothrombinase complex of coagulation is achieved by interactions at extended macromolecular recognition sites (exosites), distinct from the active site of factor Xa within the complex. We have used this formal kinetic model and a monoclonal antibody directed against Xa (alphaBFX-2b) to investigate the contributions of surfaces on the proteinase to exosite-mediated protein substrate recognition by prothrombinase. alphaBFX-2b bound reversibly to a fluorescent derivative of factor Xa (K(d) = 17.1 +/- 5.6 nm) but had no effect on active site function of factor Xa or factor Xa saturably assembled into prothrombinase. In contrast, alphaBFX-2b was a slow, tight binding inhibitor of the cleavage of either prethrombin 2 or meizothrombin des-fragment 1 by prothrombinase (K(i)(*) = 0.55 +/- 0.05 nm). Thus, alphaBFX-2b binding to factor Xa within prothrombinase selectively leads to the inhibition of protein substrate cleavage without interfering with active site function. Inhibition kinetics could adequately be accounted for by a kinetic model in which prethrombin 2 and alphaBFX-2b bind in a mutually exclusive way to prothrombinase. These are properties expected of an exosite-directed inhibitor. The site(s) on factor Xa responsible for antibody binding were evaluated by identification of immunoreactive fragments following chemical digestion of human and bovine Xa and were further confirmed with a series of recombinantly expressed fragments. These approaches suggest that residues 82-91 and 102-116 in the proteinase domain contribute to alphaBFX-2b binding. The data establish this antibody as a prototypic exosite-directed inhibitor of prothrombinase and suggest that the occlusion of a surface on factor Xa, spatially removed from the active site, is sufficient to block exosite dependent recognition of the protein substrate by prothrombinase. PMID- 11782480 TI - The structural basis for the specificity of retinoid-X receptor-selective agonists: new insights into the role of helix H12. AB - Ligands that specifically target retinoid-X receptors (RXRs) are emerging as potentially powerful therapies for cancer, diabetes, and the lowering of circulatory cholesterol. To date, RXR has only been crystallized in the absence of ligand or with the promiscuous ligand 9-cis retinoic acid, which also activates retinoic acid receptors. Here we present the structure of hRXRbeta in complex with the RXR-specific agonist LG100268 (LG268). The structure clearly reveals why LG268 is specific for the RXR ligand binding pocket and will not activate retinoic acid receptors. Intriguingly, in the crystals, the C-terminal "activation" helix (AF-2/helix H12) is trapped in a novel position not seen in other nuclear receptor structures such that it does not cap the ligand binding cavity. Mammalian two-hybrid assays indicate that LG268 is unable to release co repressors from RXR unless co-activators are also present. Together these findings suggest that RXR ligands may be inefficient at repositioning helix H12. PMID- 11782481 TI - The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch. AB - Tight junctions create a highly selective diffusion barrier between epithelial and endothelial cells by preventing the free passage of molecules and ions across the paracellular pathway. Although the regulation of this barrier is still enigmatic, there is evidence that junctional transmembrane proteins are critically involved. Recent evidence confirms the notion that occludin, a four pass integral plasma-membrane protein, is a functional component of the paracellular barrier. The overall hydrophilicity of occludin predicts two extracellular loops bounded by NH(2)- and COOH-terminal cytoplasmic domains. To date, the binding of the COOH terminus of occludin to intracellular proteins is well documented, but information concerning the function of the cytoplasmic NH(2) terminus is still lacking. Using yeast two-hybrid screening we have identified a novel interaction between occludin and the E3 ubiquitin-protein ligase Itch, a member of the HECT domain-containing ubiquitin-protein ligases. We have found that the NH(2)-terminal portion of occludin binds specifically to a multidomain of Itch, consisting of four WW motifs. This interaction has been confirmed by our results from in vivo and in vitro co-immunoprecipitation experiments. In addition, we provide evidence that Itch is specifically involved in the ubiquitination of occludin in vivo, and that the degradation of occludin is sensitive to proteasome inhibition. PMID- 11782482 TI - Purine and pyrimidine salvage in whole rat brain. Utilization of ATP-derived ribose-1-phosphate and 5-phosphoribosyl-1-pyrophosphate generated in experiments with dialyzed cell-free extracts. AB - The object of this work stems from our previous studies on the mechanisms responsible of ribose-1-phosphate- and 5-phosphoribosyl-1-pyrophosphate-mediated nucleobase salvage and 5-fluorouracil activation in rat brain (Mascia, L., Cappiello M., Cherri, S., and Ipata, P. L. (2000) Biochim. Biophys. Acta 1474, 70 74; Mascia, L., Cotrufo, T., Cappiello, M., and Ipata, P. L. (1999) Biochim. Biophys. Acta 1472, 93-98). Here we show that when ATP at "physiological concentration" is added to dialyzed extracts of rat brain in the presence of natural nucleobases or 5-fluorouracil, adenine-, hypoxanthine-, guanine-, uracil , and 5-fluorouracil-ribonucleotides are synthesized. The molecular mechanism of this peculiar nucleotide synthesis relies on the capacity of rat brain to salvage purine and pyrimidine bases by deriving ribose-1-phosphate and 5-phosphoribosyl-1 pyrophosphate from ATP even in the absence of added pentose or pentose phosphates. The levels of the two sugar phosphates formed are compatible with those of synthesized nucleotides. We propose that the ATP-mediated 5 phosphoribosyl-1-pyrophosphate synthesis occurs through the action of purine nucleoside phosphorylase, phosphopentomutase, and 5-phosphoribosyl-1 pyrophosphate synthetase. Furthering our previous observations on the effect of ATP in the 5-phosphoribosyl-1-pyrophosphate-mediated 5-fluorouracil activation in rat liver (Mascia, L., and Ipata, P. L. (2001) Biochem. Pharmacol. 62, 213-218), we now show that the ratio [5-phosphoribosyl-1-pyrophosphate]/[ATP] plays a major role in modulating adenine salvage in rat brain. On the basis of our in vitro results, we suggest that massive ATP degradation, as it occurs in brain during ischemia, might lead to an increase of the intracellular 5-phosphoribosyl-1 pyrophosphate and ribose-1-phosphate pools, to be utilized for nucleotide resynthesis during reperfusion. PMID- 11782484 TI - Plasmin reduction by phosphoglycerate kinase is a thiol-independent process. AB - Phosphoglycerate kinase (PGK) is secreted by tumor cells and facilitates reduction of disulfide bond(s) in plasmin (Lay, A. J., Jiang, X.-M., Kisker, O., Flynn, E., Underwood, A., Condron, R., and Hogg, P. J. (2000) Nature 408, 869 873). The angiogenesis inhibitor, angiostatin, is cleaved from the reduced plasmin by a combination of serine- and metalloproteinases. The chemistry of protein reductants is typically mediated by a pair of closely spaced Cys residues. There are seven Cys in human PGK, and mutation of all seven to Ala did not appreciably affect plasmin reductase activity, although some of the mutations perturbed the tertiary structure of the protein. Cys-379 and Cys-380 are close to the hinge that links the N- and C-terminal domains of PGK. Alkylation/oxidation of Cys-379 and -380 by four different thiol-reactive compounds reduced plasmin reductase activity to 7--35% of control. Binding of 3-phosphoglycerate and/or MgATP to the N- and C-terminal domains of PGK, respectively, triggers a hinge bending conformational change in the enzyme. Incubation of PGK with 3 phosphoglycerate and/or MgATP ablated plasmin reductase activity, with half maximal inhibitory effects at approximately 1 mm concentration. In summary, reduction of plasmin by PGK is a thiol-independent process, although either alkylation/oxidation of the fast-reacting Cys near the hinge or hinge bending conformational change in PGK perturbs plasmin reduction by PGK, perhaps by obstructing the interaction of plasmin with PGK or perturbing conformational changes in PGK required for plasmin reduction. PMID- 11782483 TI - Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. AB - Two treatments, fasting/refeeding and administration of liver X receptor (LXR) agonists, elevate the mRNA for sterol regulatory element-binding protein-1c (SREBP-1c) and enhance lipid synthesis in liver. These treatments do not affect the mRNA for SREBP-1a, an alternative transcript from the same gene. Through homologous recombination, we eliminated the exon encoding SREBP-1c from the mouse genome, leaving the SREBP-1a transcript intact. On a normal diet, livers of SREBP 1c(-/-) mice manifested reductions in multiple mRNAs encoding enzymes of fatty acid and triglyceride synthesis, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). In contrast, SREBP-1c(-/-) livers showed a compensatory increase in hepatic SREBP-2 mRNA, accompanied by increased mRNA levels for cholesterol biosynthetic enzymes. In fasted/refed animals, ACC and FAS mRNAs rose, but not to the same extent as in wild-type livers. The refeeding-induced increase in SREBP-1c(-/-) mice was greater than in mice lacking SREBP cleavage activating protein (SCAP), in which all nuclear SREBPs are absent. Thus, SREBP-2 and/or SREBP-1a can substitute partially for SREBP-1c in permitting an insulin mediated increase in ACC and FAS mRNAs. In contrast, mRNAs for several other lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme, glycerol-3 phosphate acyltransferase, and stearoyl-CoA desaturase-1) showed a complete failure of the normal inductive response to refeeding, indicating specific reliance on SREBP-1c. Moreover, these mRNAs, as well as multiple other lipogenic mRNAs, showed a markedly blunted response to the LXR agonist T090137, indicating an essential role of SREBP-1c in the LXR response. PMID- 11782485 TI - Genes encoding calmodulin-binding proteins in the Arabidopsis genome. AB - Analysis of the recently completed Arabidopsis genome sequence indicates that approximately 31% of the predicted genes could not be assigned to functional categories, as they do not show any sequence similarity with proteins of known function from other organisms. Calmodulin (CaM), a ubiquitous and multifunctional Ca(2+) sensor, interacts with a wide variety of cellular proteins and modulates their activity/function in regulating diverse cellular processes. However, the primary amino acid sequence of the CaM-binding domain in different CaM-binding proteins (CBPs) is not conserved. One way to identify most of the CBPs in the Arabidopsis genome is by protein-protein interaction-based screening of expression libraries with CaM. Here, using a mixture of radiolabeled CaM isoforms from Arabidopsis, we screened several expression libraries prepared from flower meristem, seedlings, or tissues treated with hormones, an elicitor, or a pathogen. Sequence analysis of 77 positive clones that interact with CaM in a Ca(2+)-dependent manner revealed 20 CBPs, including 14 previously unknown CBPs. In addition, by searching the Arabidopsis genome sequence with the newly identified and known plant or animal CBPs, we identified a total of 27 CBPs. Among these, 16 CBPs are represented by families with 2-20 members in each family. Gene expression analysis revealed that CBPs and CBP paralogs are expressed differentially. Our data suggest that Arabidopsis has a large number of CBPs including several plant-specific ones. Although CaM is highly conserved between plants and animals, only a few CBPs are common to both plants and animals. Analysis of Arabidopsis CBPs revealed the presence of a variety of interesting domains. Our analyses identified several hypothetical proteins in the Arabidopsis genome as CaM targets, suggesting their involvement in Ca(2+) mediated signaling networks. PMID- 11782486 TI - Regulation of mesangial cell hexokinase activity and expression by heparin binding epidermal growth factor-like growth factor: epidermal growth factors and phorbol esters increase glucose metabolism via a common mechanism involving classic mitogen-activated protein kinase pathway activation and induction of hexokinase II expression. AB - Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogen-activated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (> or =10 nm) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the uniform requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury. PMID- 11782487 TI - Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia. AB - In models of type 2 diabetes the expression of beta-cell genes is altered, but these changes have not fully explained the impairment in beta-cell function. We hypothesized that changes in beta-cell phenotype and global alterations in both carbohydrate and lipid pathways are likely to contribute to secretory abnormalities. Therefore, expression of genes involved in carbohydrate and lipid metabolism were analyzed in islets 4 weeks after 85-95% partial pancreatectomy (Px) when beta-cells have impaired glucose-induced insulin secretion and ATP synthesis. Px rats after 1 week developed mild to severe hyperglycemia that was stable for the next 3 weeks, whereas neither plasma triglyceride, non-esterified fatty acid, or islet triglyceride levels were altered. Expression of peroxisome proliferator-activated receptors (PPARs), with several target genes, were reciprocally regulated; PPARalpha was markedly reduced even at low level hyperglycemia, whereas PPARgamma was progressively increased with increasing hyperglycemia. Uncoupling protein 2 (UCP-2) was increased as were other genes barely expressed in sham islets including lactate dehydrogenase-A (LDH-A), lactate (monocarboxylate) transporters, glucose-6-phosphatase, fructose-1,6 bisphosphatase, 12-lipoxygenase, and cyclooxygenase 2. On the other hand, the expression of beta-cell-associated genes, insulin, and GLUT2 were decreased. Treating Px rats with phlorizin normalized hyperglycemia without effecting plasma fatty acids and reversed the changes in gene expression implicating the importance of hyperglycemia per se in the loss of beta-cell phenotype. In addition, parallel changes were observed in beta-cell-enriched tissue dissected by laser capture microdissection from the central core of islets. In conclusion, chronic hyperglycemia leads to a critical loss of beta-cell differentiation with altered expression of genes involved in multiple metabolic pathways diversionary to normal beta-cell glucose metabolism. This global maladaptation in gene expression at the time of increased secretory demand may contribute to the beta cell dysfunction found in diabetes. PMID- 11782488 TI - Hydrogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells: potential role in cell survival following oxidative insults. AB - Reactive oxygen species, generated by reduction-oxidation (redox) reactions, have been recognized as one of the major mediators of ischemia and reperfusion injury in the brain. Reactive oxygen species-induced cerebral events are attributable, in part, to the change in intracellular signaling molecules including mitogen activated protein (MAP) kinases. Big MAP kinase 1 (BMK1), also known as ERK5, is a newly identified member of the MAP kinase family and has been reported to be sensitive to oxidative stress. In the present study, we examined the effect of H(2)O(2) on BMK1 activity in PC12 cells, and we investigated the pathophysiological implication of BMK1. Findings showed that BMK1 was rapidly and significantly activated by H(2)O(2) in a concentration-dependent manner in PC12 cells. BMK1 activation by H(2)O(2) was inhibited by both PD98059 and U0126, which were reported to inhibit MEK5 as well as MEK1/2. c-Src was suggested to be involved in BMK1 activation from the experiments with herbimycin A and PP2, specific inhibitors of Src family kinases. Transfection of kinase-inactive Src also inhibited H(2)O(2)-induced BMK1 activation. In addition, H(2)O(2) treatment of cells induced an enhancement of DNA binding activity of MEF2C, a downstream transcription factor of BMK1 in PC12 cells. Finally, pretreatment of cells with PD98059 and U0126 resulted in an increase in cell death including apoptosis by H(2)O(2) in ERK1/2 down-regulated cells as well as in intact PC12 cells. These findings suggest that c-Src mediated BMK1 activation by H(2)O(2) may counteract ischemic cellular damage probably through the activation of MEF2C transcription factor. PMID- 11782490 TI - Dynacortin is a novel actin bundling protein that localizes to dynamic actin structures. AB - Dynacortin is a novel protein that was discovered in a genetic suppressor screen of a Dictyostelium discoideum cytokinesis-deficient mutant cell line devoid of the cleavage furrow actin bundling protein, cortexillin I. While dynacortin is highly enriched in the cortex, particularly in cell-surface protrusions, it is excluded from the cleavage furrow cortex during cytokinesis. Here, we describe the biochemical characterization of this new protein. Purified dynacortin is an 80-kDa dimer with a large 5.7-nm Stokes radius. Dynacortin cross-links actin filaments into parallel arrays with a mole ratio of one dimer to 1.3 actin monomers and a 3.1 microm K(d). Using total internal reflection fluorescence microscopy, GFP-dynacortin and the actin bundling protein coronin-GFP are seen to concentrate in highly dynamic cortical structures with assembly and disassembly half-lives of about 15 s. These results indicate that cells have evolved different actin-filament cross-linking proteins with complementary cellular distributions that collaborate to orchestrate complex cell shape changes. PMID- 11782489 TI - Long term regulation of aquaporin-2 expression in vasopressin-responsive renal collecting duct principal cells. AB - Fine regulation of water reabsorption by the antidiuretic hormone [8 arginine]vasopressin (AVP) occurs in principal cells of the collecting duct and is largely dependent on regulation of the aquaporin-2 (AQP2) water channel. AVP inducible long term AQP2 expression was investigated in immortalized mouse cortical collecting duct principal cells. Combined RNase protection assay, Western blot, and immunofluorescence analyses revealed that physiological concentrations of AVP added to the basal side, but not to the apical side, of cells grown on filters induced both AQP2 mRNA and apical protein expression. The stimulatory effect of AVP on AQP2 expression followed a V(2) receptor-dependent pathway because [deamino-8-d-arginine]vasopressin (dDAVP), a specific V(2) receptor agonist, produced the same effect as AVP, whereas the V(2) antagonist SR121463B antagonized action of both AVP and dDAVP. Moreover, forskolin and cyclic 8-bromo-AMP fully reproduced the effects of AVP on AQP2 expression. Analysis of protein degradation pathways showed that inhibition of proteasomal activity prevented synthesis of AVP-inducible AQP2 mRNA and protein. Once synthesized, AQP2 protein was quickly degraded, a process that involves both the proteasomal and lysosomal pathways. This is the first study that delineates induction and degradation mechanisms of AQP2 endogenously expressed by a renal collecting duct principal cell line. PMID- 11782491 TI - Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. AB - The Nf2 tumor suppressor gene product merlin is related to the membrane cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42 dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. PMID- 11782492 TI - E. coli O157 persistence in the environment. PMID- 11782494 TI - 2001 Fred Griffith review lecture. Immigration control of DNA in bacteria: self versus non-self. PMID- 11782495 TI - The enigma of the origin of life and its timing. PMID- 11782496 TI - Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. AB - High-affinity iron uptake by a ferrous permease in the opportunistic pathogen Candida albicans is required for virulence. Here this iron uptake system has been characterized by investigating three distinct activities: an externally directed surface ferric reductase, a membrane-associated PPD (p-phenylenediamine) oxidase and a cellular ferrous iron transport activity. Copper was required for the PPD oxidase and ferrous transport activities. In contrast, copper was not required for iron uptake from siderophores. Addition of iron to the growth medium repressed ferric reductase and ferrous transport, indicating homeostatic regulation. To identify the genes involved, orthologous mutants of Saccharomyces cerevisiae were transformed with a genomic library of C. albicans. CFL95, a gene with sequence similarity to ferric reductases, restored reductase activity to the orthologous S. cerevisiae mutant. CaFTR2 and CaFTR1, genes with homology to ferrous permeases, conferred ferrous transport activity to the orthologous S. cerevisiae mutant. However, neither a genomic library nor CaFET99, a multicopper oxidase homologue and candidate gene for the PPD oxidase, complemented the S. cerevisiae mutant, possibly because of problems with targeting or assembly. Transcripts for CFL95, CaFTR1 and CaFET99 were strongly repressed by iron, whereas the CaFTR2 transcript was induced by iron. Deletion of the TUP1 regulator perturbed the homeostatic control of reductive iron uptake. Incidentally, iron starvation was noted to induce flavin production and this was misregulated in the absence of TUP1 control. The opposite regulation of two iron permease genes and the role of TUP1 indicate that the process of iron acquisition by C. albicans may be more complex and potentially more adaptable than by S. cerevisiae. PMID- 11782497 TI - Secretion of active anti-Ras single-chain Fv antibody by the yeasts Yarrowia lipolytica and Kluyveromyces lactis. AB - Yarrowia lipolytica and Kluyveromyces lactis secretion vectors were constructed and assessed for the expression of heterologous proteins. An anti-Ras single chain antibody fragment (scFv) coding sequence was fused in-frame to different pre- or prepro-regions, or downstream from a reporter secretory gene (Arxula adeninivorans glucoamylase), separated by a Kex2 protease (Kex2p)-like processing sequence. Both organisms are able to secrete soluble scFv, with yields depending on the nature of the expression cassette, up to levels ranging from 10 to 20 mg l(-1). N-terminal sequence analysis of the purified scFv showed that fusions are correctly processed to the mature scFv by a signal peptidase or a Kex2p-type endoprotease present in Y. lipolytica and K. lactis. The scFv protein also retains the capacity to bind to a glutathioneS-transferase (GST)-Harvey Ras(Val12) fusion, indicating that the antibody is functional. These results indicate that the yeasts Y. lipolytica and K. lactis have potential for industrial production of soluble and active scFv. PMID- 11782498 TI - The candicidin gene cluster from Streptomyces griseus IMRU 3570. AB - A 205 kb DNA region from Streptomyces griseus IMRU 3570, including the candicidin biosynthetic gene cluster, was cloned and partially sequenced. Analysis of the sequenced DNA led to identification of genes encoding part of a modular polyketide synthase (PKS), genes for thioesterase, macrolactone ring modification, mycosamine biosynthesis and attachment to the macrolide ring, candicidin export and regulatory proteins. It represents the first extensive genetic characterization of an aromatic polyene macrolide antibiotic biosynthetic gene cluster. Of particular interest is the presence of the CanP1 loading domain (the first described as responsible for the activation of an aromatic starter unit) and the polypeptide CanP3 (carrying modules for the formation of five out of seven conjugated double bonds). Disruption of the pabAB gene that encodes the starter unit of candicidin abolished its production [which was restored when exogenous p-aminobenzoic acid (PABA) was supplied to the culture] and resulted in an enhanced production of another antifungal compound that is barely detected in the wild-type. PMID- 11782499 TI - Characterization of the attP site of the integrative element pSAM2 from Streptomyces ambofaciens. AB - pSAM2 is integrated into the Streptomyces ambofaciens chromosome through site specific recombination between the element (attP) and the chromosomal (attB) site. The 43 kDa integrase protein encoded by pSAM2 catalyses this recombination event. Tools have been developed to study site-specific recombination in Escherichia coli. In vivo studies showed that a 360 bp fragment of attP is required for efficient site-specific recombination and that int can be provided in trans. pSAM2 integrase was purified and overexpressed in E. coli and Int binding at the attP site was studied. DNaseI footprinting revealed two sites that bind integrase strongly and appear to be symmetrical with regard to the core site. These two P1/P2 arm-type sites both contain a 17 bp motif that is identical except at one position, GTCACGCAG(A/T)TAGACAC. P1 and P2 are essential for site specific recombination. PMID- 11782500 TI - Investigation of in vivo cross-talk between key two-component systems of Escherichia coli. AB - Intracellular signal transfer in bacteria is dominated by phosphoryl transfer between conserved transmitter and receiver domains in regulatory proteins of so called two-component systems. Escherichia coli contains 30 such systems, which allow it to modulate gene expression, enzyme activity and the direction of flagellar rotation. The authors have investigated whether, and to what extent, these separate systems form (an) interacting network(s) in vivo, focussing on interactions between four major systems, involved in the responses to the availability of phosphorylated sugars (Uhp), phosphate (Pho), nitrogen (Ntr) and oxygen (Arc). Significant cross-talk was not detectable in wild-type cells. Decreasing expression levels of succinate dehydrogenase (reporting Arc activation), upon activation of the Pho system, appeared to be independent of signalling through PhoR. Cross-talk towards NtrC did occur, however, in a ntrB deletion strain, upon joint activation of Pho, Ntr and Uhp. UhpT expression was demonstrated when cells were grown on pyruvate, through non-cognate phosphorylation of UhpA by acetyl phosphate. PMID- 11782501 TI - Fast lysis of Escherichia coli filament cells requires differentiation of potential division sites. AB - Periodic activation of zonal peptidoglycan (murein) synthesis at division sites in Escherichia coli has been reported recently. Zonal synthesis is responsible for septum formation, whereas elongation of the cell sacculus is performed by diffuse insertion of precursors. Zonal synthesis can be triggered in ftsA, ftsQ and ftsI (pbpB) division mutants growing as filaments at the restrictive temperature, but not in ftsZ mutant strains. The lytic response to beta-lactams of cells able or unable to periodically trigger a zonal mode of murein synthesis could be substantially different. Therefore, we investigated the response to the bacteriolytic beta-lactam cefsulodin of ftsZ and ftsI mutants growing at the restrictive (42 degrees C) temperature. The ftsI cells lysed early and quickly after addition of the antibiotic. Sacculi of lysed cells were transversely cut in a very sharp way. In contrast the ftsZ strain lysed late and slowly after addition of the antibiotic and sacculi showed a generalized weakening of the murein network and extended breaks with a frayed appearance. No transversely cut sacculi comparable to those seen in the ftsI samples were found. Our results strongly support that beta-lactam-induced lysis occurs preferentially at division sites because of the activation of zonal murein synthesis at the initiation of septation. PMID- 11782502 TI - Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. AB - Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR by expression of an unstable version of the green-fluorescent protein (Gfp). Gfp-based reporter technology has been applied for non-destructive, single-cell-level detection of quorum sensing in laboratory-based P. aeruginosa biofilms. It is reported that a synthetic halogenated furanone compound, which is a derivative of the secondary metabolites produced by the Australian macroalga Delisea pulchra, is capable of interfering with AHL-mediated quorum sensing in P. aeruginosa. It is demonstrated that the furanone compound specifically represses expression of a PlasB-gfp reporter fusion without affecting growth or protein synthesis. In addition, it reduces the production of important virulence factors, indicating a general effect on target genes of the las quorum sensing circuit. The furanone was applied to P. aeruginosa biofilms established in biofilm flow chambers. The Gfp based analysis reveals that the compound penetrates microcolonies and blocks cell signalling and quorum sensing in most biofilm cells. The compound did not affect initial attachment to the abiotic substratum. It does, however, affect the architecture of the biofilm and enhances the process of bacterial detachment, leading to a loss of bacterial biomass from the substratum. PMID- 11782503 TI - kdsA mutations affect FtsZ-ring formation in Escherichia coli K-12. AB - No one has, as yet, addressed the relationship between the nature of the outer membrane and cell division. kdsA encodes 3-deoxy-D-manno-octulosonic acid (KDO) 8 phosphate synthetase which catalyses the first step in the synthesis of KDO, the linker between lipid A and oligosaccharide of lipopolysaccharide (LPS). Seven temperature-sensitive mutants containing missense mutations in kdsA were affected in the production of KDO and all mutants stopped dividing at 41 degrees C and formed filaments with either one or no FtsZ ring. All observed defects were reversed by the plasmid-borne wild-type kdsA gene. Western blotting analysis, however, demonstrated that the amount of FtsZ protein was not affected by the mutation. The mutants were more susceptible to various hydrophobic materials, such as novobiocin, eosin Y and SDS at 36 degrees C. Methylene blue, however, restored kdsA mutant growth. Plasmid-borne wild-type msbA, encoding a lipid A transporter in the ABC family, partially suppressed kdsA mutation. A mutation of lpxA, functioning at the first stage in lipid A biosynthesis, inhibited both cell division and growth, producing short filaments. These results indicate that the instability of the outer membrane, caused by the defect in KDO biosynthesis, affects FtsZ-ring formation. PMID- 11782504 TI - The starvation-stress response of Salmonella enterica serovar Typhimurium requires sigma(E)-, but not CpxR-regulated extracytoplasmic functions. AB - Starvation of Salmonella enterica serovar Typhimurium (S. Typhimurium) for an exogenous source of carbon and energy (C-starvation) induces the starvation stress response (SSR). The SSR functions to (i) maintain viability during long term C-starvation and (ii) generate cross-resistance to other environmental stresses. The SSR is, at least partially, under the control of the alternative sigma factor, sigma(S). It is hypothesized that C-starvation causes cell envelope stresses that could induce the sigma(E) and/or Cpx regulons, both of which control extracytoplasmic functions and, thus, may play a role in the regulation of the SSR. In support of this hypothesis, Western blot analysis showed that the relative levels of sigma(E) increased during C-starvation, peaking after approximately 72 h of C-starvation; in contrast, CpxR levels remained relatively constant from exponential phase up to 72 h of C-starvation. To determine if sigma(E), and thus the regulon it controls, is an essential component of the SSR, several mutant strains were compared for their abilities to survive long-term C starvation and to develop C-starvation-induced (CSI) cross-resistances. An rpoE mutant strain was significantly impaired in both long-term C-starvation survival (LT-CSS) and in CSI cross-resistance to challenges with 20 mM H(2)O(2) for 40 min, 55 degrees C for 16 min, pH 3.1 for 60 min and 870.2 USP U polymyxin B ml( 1) (PmB) for 60 min, to varying degrees. These results suggest that C-starvation can generate signals that induce the rpoE regulon and that one or more members of the sigma(E) regulon are required for maximal SSR function. Furthermore, evidence suggests that the sigma(E) and sigma(S) regulons function through separate mechanisms in the SSR. In contrast, C-starvation does not appear to generate signals required for Cpx regulon induction which support the findings that it is not required for LT-CSS or cross-resistance to H(2)O(2), pH 3.1 or PmB challenges. However, it was required to achieve maximal cross-resistance to 55 degrees C. Therefore, sigma(E) is a key regulatory component of the SSR and represents an additional sigma factor required for the SSR of Salmonella. PMID- 11782505 TI - Regulation of carbon utilization by sulfur availability in Escherichia coli and Salmonella typhimurium. AB - Different pleiotropic transcriptional regulators are known to function in the coordination of regulons concerned with carbon, nitrogen, sulfur, phosphorus and iron metabolism, but how expression profiles of these different regulons are coordinated with each other is not known. The basis for the effects of cysB mutations on carbon utilization in Escherichia coli and Salmonella typhimurium was examined. cysB mutations affected the utilization of some carbon sources more than others and these effects could be partially, but not completely, reversed by the inclusion of cysteine or djenkolate in the growth medium. Assays of transport systems and enzymes concerned with glucitol and alanine utilization showed that these activities were depressed in cysB mutants relative to isogenic wild-type strains, and cysteine or djenkolate present in the growth media partially restored these activities. Using transcriptional fusions to the fdo (formate dehydrogenase) and gut (glucitol) operons, it was shown that decreased expression resulted from defects at the transcriptional level. Furthermore, the effects of loss of CysB were much less pronounced under conditions of catabolite repression than in the absence of a catabolite-repressing carbon source, and cAMP largely reversed the effect of the loss of CysB. Comparable effects were seen for E. coli lacZ gene expression under the control of its own native promoter, and sulfur limitation in a cysB mutant depressed net cAMP production in a cAMP phosphodiesterase mutant. Adenylate cyclase thus appears to be responsive to sulfur deprivation. These observations may have physiological significance allowing carbon and sulfur regulon coordination during the growth of enteric bacteria in response to nutrient availability. PMID- 11782506 TI - AcnC of Escherichia coli is a 2-methylcitrate dehydratase (PrpD) that can use citrate and isocitrate as substrates. AB - Escherichia coli possesses two well-characterized aconitases (AcnA and AcnB) and a minor activity (designated AcnC) that is retained by acnAB double mutants and represents no more than 5% of total wild-type aconitase activity. Here it is shown that a 2-methylcitrate dehydratase (PrpD) encoded by the prpD gene of the propionate catabolic operon (prpRBCDE) is identical to AcnC. Inactivation of prpD abolished the residual aconitase activity of an AcnAB-null strain, whereas inactivation of ybhJ, an unidentified acnA paralogue, had no significant effect on AcnC activity. Purified PrpD catalysed the dehydration of citrate and isocitrate but was most active with 2-methylcitrate. PrpD also catalysed the dehydration of several other hydroxy acids but failed to hydrate cis-aconitate and related substrates containing double bonds, indicating that PrpD is not a typical aconitase but a dehydratase. Purified PrpD was shown to be a monomeric iron-sulphur protein (M(r) 54000) having one unstable [2Fe-2S] cluster per monomer, which is needed for maximum catalytic activity and can be reconstituted by treatment with Fe(2+) under reducing conditions. PMID- 11782507 TI - Fur-mediated transcriptional and post-transcriptional regulation of FeSOD expression in Escherichia coli. AB - Fur (ferric uptake regulation protein) activates sodB expression, increasing expression levels by a factor of seven and sodB transcript stability by a factor of three. Post-transcriptional regulation of sodB was investigated by searching for endoribonucleases that might be involved in sodB mRNA degradation. The activation of sodB expression was significantly reduced if both the RNaseE and RNaseIII genes were mutated. This correlated with cleavage at a palindromic sequence located in the 5' untranslated region of the sodB transcript. An RNA binding assay showed that Fur did not directly protect the sodB transcript. It was hypothesized that the persistence of Fur-mediated activation of sodB expression in the RNase double mutant was probably due to an effect at the transcriptional level. Therefore, it was investigated whether Fur had a direct transcriptional effect in vitro. Fur bound the sodB promoter region with low affinity, but it was not able to increase sodB transcription. H-NS-mediated repression of sodB expression, which has been shown to be Fur-dependent, was characterized. No DNA-bending region was identified in the sodB promoter region. H-NS did not interfere with the post-transcriptional effect of Fur. Fur-dependent H-NS and the Fur post-transcriptional effect were not additive. This suggests that Fur and H-NS effects are indirect and may be mediated by a common intermediate. PMID- 11782508 TI - Immunodominant membrane proteins from two phytoplasmas in the aster yellows clade (chlorante aster yellows and clover phyllody) are highly divergent in the major hydrophilic region. AB - The mechanisms by which phytoplasmas interact with their hosts are not understood. Mollicute membrane proteins may play a role in such interactions and therefore the amp genes encoding immunodominant proteins from two phytoplasmas, aster yellows and clover phyllody, which fall within the largest taxonomic subclade of the phytoplasmas, have been cloned and characterized. The putative translation products, antigenic membrane proteins (Amps), of these genes have properties which are typical for bacterial membrane proteins, and which suggest that each has a single large extracellular hydrophilic domain held by a transmembrane region near the C-terminus, with only a short C-terminal intracellular sequence. Both of the Amps characterized here have bacterial leader sequences which are cleaved during maturation. Whilst the signal peptide and transmembrane regions of the two proteins are very similar, the major hydrophilic domains are highly divergent in both size and sequence. The Amps from the two phytoplasmas are also different in structure and sequence from the immunodominant membrane proteins of three other phytoplasmas whose genes have been cloned previously. PMID- 11782509 TI - Immunological response mounted by Aboriginal Australians living in the Northern Territory of Australia against Streptococcus pyogenes serum opacity factor. AB - Streptococcus pyogenes (Group A streptococcus) interacts with host fibronectin via a number of distinct surface components. The streptococcal serum opacity factor (SOF) is a cell-surface protein of S. pyogenes which causes opalescence of human serum and mediates bacterial binding to fibronectin. In this study, hexahistidyl-tagged fusion proteins encompassing full-length SOF, and domains of SOF encompassing opacity factor activity and fibronectin-binding regions, were used in the characterization of the Aboriginal immune response to SOF. Anti-SOF serum IgG responses were found to be significantly higher (P<0.0001) in Aboriginal adults and children when compared to a non-Aboriginal adult group. The Aboriginal immune response against the fibronectin-binding region of SOF was significantly reduced when compared to the response against the whole SOF protein and N-terminal domains examined in this study (P<0.001). This pattern of immune response was also observed in rabbits immunized with recombinant SOF. Comparison of the deduced amino acid sequence of SOF from a number of common Australian isolates with other SOF sequences revealed that the N-terminus of SOF exhibits sequence similarity values ranging from 42.9% to 96.5%. The C-terminus containing the fibronectin-binding domain and membrane-spanning regions was more highly conserved, exhibiting sequence similarity values ranging from 84.6% to 100% within the fibronectin-binding repeats. These data suggest that the immune response against SOF is directed toward the variable N-terminus of the SOF protein. Phylogenetic analysis indicated that the sof genes of S. pyogenes do not exhibit geographical variation. PMID- 11782510 TI - Differentiation of plasmids in marine diazotroph assemblages determined by randomly amplified polymorphic DNA analysis. AB - Nitrogen fixation by diazotrophic bacteria is a significant source of new nitrogen in salt marsh ecosystems. Recent studies have characterized the physiological and phylogenetic diversity of oxygen-utilizing diazotrophs isolated from the rhizoplanes of spatially separated intertidal macrophyte habitats. However, there is a paucity of information regarding the traits encoded by and the diversity of plasmids occurring in this key ecological functional group. Five hundred and twenty-one isolates cultivated from the rhizoplanes of Juncus roemarianus, Spartina patens and different growth forms (short-form and tall form) of Spartina alterniflora were screened for the presence of plasmids. One hundred and thirty-four diazotrophs carrying plasmids that ranged in size from 2 to >100 kbp were identified. The majority of the marine bacteria contained one plasmid. Diazotrophs from the short-form S. alterniflora rhizoplane contained significantly fewer plasmids relative to isolates from tall-form S. alterniflora, J. roemarianus and S. patens. Although some plasmids exhibited homology to a nifH gene probe, the majority of the plasmids were classified as cryptic. Two oligonucleotide primers were developed to facilitate genotypic typing of the endogenously isolated marine plasmids by the randomly amplified polymorphic DNA (RAPD)-PCR technique. These primers proved to be more effective than 21 commercially available primers tested to generate RAPD-PCR patterns. Analysis of the RAPD-PCR patterns indicated as many as 71 different plasmid genotypes occurring in diazotroph bacterial assemblages within and between the four different salt marsh grass rhizoplane habitats investigated in this study. PMID- 11782511 TI - Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans. AB - The Ras1 signal transduction pathway controls the ability of the pathogenic fungus Cryptococcus neoformans to grow at high temperatures and to mate. A second RAS gene was identified in this organism. RAS2 is expressed at a very low level compared to RAS1, and a ras2 mutation caused no alterations in vegetative growth rate, differentiation or virulence factor expression. The ras2 mutant strain was equally virulent to the wild-type strain in the murine inhalational model of cryptococcosis. Although a ras1 ras2 double mutant strain is viable, mutation of both RAS genes results in a decreased growth rate at all temperatures compared to strains with either single mutation. Overexpression of the RAS2 gene completely suppressed the ras1 mutant mating defect and partially suppressed its high temperature growth defect. After prolonged incubation at a restrictive temperature, the ras1 mutant demonstrated actin polarity defects that were also partially suppressed by RAS2 overexpression. These studies indicate that the C. neoformans Ras1 and Ras2 proteins share overlapping functions, but also play distinct signalling roles. Our findings also suggest a mechanism by which Ras1 controls growth of this pathogenic fungus at 37 degrees C, supporting a conserved role for Ras homologues in microbial cellular differentiation, morphogenesis and virulence. PMID- 11782512 TI - Multiple origins of hybrid strains of Cryptococcus neoformans with serotype AD. AB - Cryptococcus neoformans is a major pathogen of humans throughout the world. Using commercial mAbs to capsular epitopes, strains of C. neoformans manifest five distinct serotypes--A, B, C, D and AD. Previous studies demonstrated significant divergence among serotypes A, B, C and D, which are thought to be haploid. In this study the origins and evolution of strains of serotype AD were investigated. A portion (537 bp) of the laccase gene was cloned and sequenced from 14 strains of serotype AD. Each strain contained two different alleles and sequences for both alleles were obtained. These sequences were compared to those from serotypes A, B, C and D. This analysis indicated that each of the 14 serotype AD strains contained two phylogenetically distinct haplotypes: one haplotype was highly similar to the serotype A group and the other to the serotype D group. To explain the origins of these serotype AD strains, genealogical analysis is consistent with at least three recent and independent hybridization events. The results demonstrate that the evolution of C. neoformans is continuing and dynamic. PMID- 11782513 TI - Antisense repression in Cryptococcus neoformans as a laboratory tool and potential antifungal strategy. AB - Antisense repression was used as a method to alter gene function in the human pathogenic fungus Cryptococcus neoformans. The calcineurin A gene (CNA1) and the laccase gene (LAC1) were targeted since disruption of these loci results in phenotypes that are easy to screen (temperature sensitivity and lack of melanin, respectively). Serotype D yeasts were transformed with a plasmid containing the CNA1 cDNA in an antisense orientation under the control of the inducible GAL7 promoter, and serotype A yeasts were transformed with a plasmid containing the LAC1 cDNA in an antisense orientation under the control of the constitutive actin promoter. The calcineurin transformants demonstrated a temperature-sensitive phenotype only when grown on galactose, and the laccase transformants had decreased melanin production. Northern blot analysis of the calcineurin antisense transformants confirmed that the inducible phenotype was associated with a decrease in the native CNA1 transcript levels. Furthermore, it was possible to modestly impair growth of C. neoformans at 37 degrees C by using a 30 bp antisense oligonucleotide targeting CNA1. Antisense repression is now available as a tool for molecular studies in this organism, and may be applicable to other human-pathogenic fungi that have less amenable genetic systems. PMID- 11782514 TI - Evidence for degradation of 2-chlorophenol by enrichment cultures under denitrifying conditions. AB - Although chlorophenol (CP) degradation has been studied, no bacterium responsible for degradation of CP under denitrifying conditions has been isolated. Moreover, little substantial evidence for anaerobic degradation of CPs coupled with denitrification is available even for mixed cultures. Degradation of CP [2-CP, 3 CP, 4-CP, 2,4-dichlorophenol (DCP) or 2,6-DCP] under denitrifying conditions was examined in anaerobic batch culture inoculated with activated sludge. Although 3 CP, 4-CP, 2,4-DCP and 2,6-DCP were not stably degraded, 2-CP was degraded and its degradation capability was sustained in a subculture. However, the rate of 2-CP degradation was not significantly enhanced by subculturing. In 2-CP-degrading cultures, nitrate was consumed stoichiometrically and concomitantly during 2-CP degradation, and a dechlorination intermediate was not detected, suggesting that 2-CP degradation was coupled with nitrate reduction. A 2-CP-degrading enrichment culture degraded 2-CP in the presence of nitrate, but did not in the absence of nitrate or the presence of sulfate. This suggests that the enrichment culture strictly requires nitrate for degradation of 2-CP. The apparent specific growth rate of the 2-CP degrading species was 0.0139 d(-1). Thus the apparent doubling time of the 2-CP-degrading population in the enrichment culture was greater than 50 d, which may explain difficulty in enrichment and isolation of micro-organisms responsible for CP degradation under denitrifying conditions. PMID- 11782515 TI - A broad-host-range vector of incompatibility group Q can work as a plasmid vector in Neisseria meningitidis: a new genetical tool. AB - Plasmid pHT128, a derivative of the broad-host-range IncQ vector pGSS33, was successfully introduced into Neisseria meningitidis. Under optimal conditions, pHT128 was transferred from Escherichia coli to N. meningitidis by triparental conjugation at a frequency of 10(-5)-10(-6). The copy number of pHT128 in N. meningitidis was almost the same as in E. coli, in which the copy number of IncQ plasmids per chromosome is estimated to be 10. pHT128 was maintained as an episome in N. meningitidis in the presence of chloramphenicol, a marker of the plasmid. It was also shown that an opc or pilE1 gene cloned on pHT128 could be expressed in N. meningitidis under control of the tac promoter and could complement a mutation of opc or pilE1, respectively. In addition, the conjugational introduction of pHT128 into N. meningitidis was demonstrated to be independent of natural transformation competence. All the results indicate that pHT128 is a useful vector for N. meningitidis as a new genetical tool. PMID- 11782516 TI - Clostridium perfringens alpha-toxin induces rabbit neutrophil adhesion. AB - Clostridium perfringens alpha-toxin, which is one of the main agents involved in the development of gas gangrene, stimulates O(2)(-)production in neutrophils. Exposure of rabbit neutrophils to the alpha-toxin induced firm adhesion of the cells to fibrinogen and fibronectin. Incubation of rabbit neutrophils and neutrophil lysates with alpha-toxin led to the production of diacylglycerol (DG) and L-alpha-phosphatidic acid (PA), respectively. The toxin-induced DG and PA formation preceded the toxin-induced adhesion of the neutrophils to fibrinogen and fibronectin, and the production of O(2)(-). Pertussis toxin inhibited the alpha-toxin-induced formation of PA, the adhesion of the neutrophils to fibrinogen and production. GTP gamma S stimulated the events induced by the alpha toxin, whereas GDP beta S inhibited them. The alpha-toxin stimulated phosphorylation of a protein with a molecular mass of about 40 kDa. In addition, treatment of the cells with 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol-12,13 dibutyrate (PDBu) stimulated cell adhesion, production of and phosphorylation of the 40 kDa protein, but had no effect on the formation of PA. The events induced by the presence of OAG and PDBu were not inhibited by pertussis toxin. Protein kinase C inhibitors, H-7, staurosporine and chelerythrine, blocked alpha-toxin induced adhesion, production of O(2)(-)and phosphorylation of the 40 kDa protein. These observations suggested that alpha-toxin-stimulated adhesion to the matrix and production were due to the formation of DG, through activation of phospholipid metabolism by a pertussis-toxin-sensitive GTP-binding protein, followed by activation of protein kinase C by DG. PMID- 11782517 TI - A newly described cellulosomal cellobiohydrolase, CelO, from Clostridium thermocellum: investigation of the exo-mode of hydrolysis, and binding capacity to crystalline cellulose. AB - The sequence of the celO gene from Clostridium thermocellum F7 was determined. The gene product, cellulase CelO (Ct-Cel5F), had a modular structure consisting of a carbohydrate-binding module of the CBM3 family and a catalytic domain of the glycosyl hydrolase family 5. The presence of the dockerin module indicated that the enzyme was a component of the cellulosome complex. The thermostable recombinant gene product was active on cellodextrins, barley beta-glucan, carboxymethylcellulose and insoluble cellulose. Cellobiose was the only product released from amorphic and crystalline cellulose, cellotetraose and higher cello oligosaccharides, identifying CelO as a cellobiohydrolase. The cleavage pattern of p-nitrophenyl beta-D-cellotetraoside, blockage of the hydrolysis of NaBH(4) reduced cellopentaose and the reduction in substrate viscosity suggested activity from the reducing end in a processive mode after making random cuts. Binding to insoluble, i.e. amorphous, and crystalline cellulose was mediated by the carbohydrate-binding module CBM3b, with a preference for the crystalline substrate. PMID- 11782518 TI - Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. AB - The design and evaluation of a set of universal primers and probe for the amplification of 16S rDNA from the Domain Bacteria to estimate total bacterial load by real-time PCR is reported. Broad specificity of the universal detection system was confirmed by testing DNA isolated from 34 bacterial species encompassing most of the groups of bacteria outlined in Bergey's Manual of Determinative Bacteriology. However, the nature of the chromosomal DNA used as a standard was critical. A DNA standard representing those bacteria most likely to predominate in a given habitat was important for a more accurate determination of total bacterial load due to variations in 16S rDNA copy number and the effect of generation time of the bacteria on this number, since rapid growth could result in multiple replication forks and hence, in effect, more than one copy of portions of the chromosome. The validity of applying these caveats to estimating bacterial load was confirmed by enumerating the number of bacteria in an artificial sample mixed in vitro and in clinical carious dentine samples. Taking these parameters into account, the number of anaerobic bacteria estimated by the universal probe and primers set in carious dentine was 40-fold greater than the total bacterial load detected by culture methods, demonstrating the utility of real-time PCR in the analysis of this environment. PMID- 11782519 TI - Quantitative speciation of sulfur in bacterial sulfur globules: X-ray absorption spectroscopy reveals at least three different species of sulfur. AB - X-ray absorption near edge structure (XANES) spectroscopy at the sulfur K-edge was applied to probe the speciation of sulfur of metabolically different sulfur accumulating bacteria in situ. Fitting the spectra using a least-square fitting routine XANES reveals at least three different forms of sulfur in bacterial sulfur globules. Cyclooctasulfur dominates in the sulfur globules of Beggiatoa alba and the very recently described giant bacterium Thiomargarita namibiensis. A second type of sulfur globules is present in Acidithiobacillus ferrooxidans: here the sulfur occurs as polythionates. In contrast, in purple and green sulfur bacteria the sulfur mainly consists of sulfur chains, irrespective of whether it is accumulated in globules inside or outside the cells. These results indicate that the speciation of sulfur in the sulfur globules reflects the different ecological and physiological properties of different metabolic groups of bacteria. PMID- 11782520 TI - Effect of nutrient limitation on biofilm formation and phosphatase activity of a Citrobacter sp. AB - A phosphatase-overproducing Citrobacter sp. (NCIMB 40259) was grown in an air lift reactor in steady-state continuous culture under limitation of carbon, phosphorus or nitrogen. Substantial biofilm formation, and the highest phosphatase activity, were observed under lactose limitation. However, the total amount of biofilm wet biomass and the phosphatase specific activity were reduced in phosphorus- or nitrogen-limited cultures or when glucose was substituted for lactose as the limiting carbon source. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) showed differences in cell and biofilm morphology in relation to medium composition. Electron microscopy suggested that the differences in biofilm formation may relate to differential expression of fimbriae on the cell surface. PMID- 11782521 TI - The metabolism of 2-methyladenosine in Mycobacterium smegmatis. AB - 2-Methyladenosine (methyl-ado) has demonstrated selective activity against Mycobacterium tuberculosis, which indicates that differences in the substrate preferences between mycobacterial and human purine metabolic enzymes can be exploited to develop novel drugs for the treatment of mycobacterial diseases. Therefore, in an effort to better understand the reasons for the anti mycobacterial activity of methyl-ado, its metabolism has been characterized in Mycobacterium smegmatis. In a wild-type strain, methyl-ado was phosphorylated by adenosine kinase to methyl-AMP, which was further converted to methyl-ATP and incorporated into RNA. In contrast, a mutant strain of M. smegmatis was isolated that was resistant to methyl-ado, deficient in adenosine kinase activity and was not able to generate methyl-ado metabolites in cells treated with methyl-ado. These results indicated that phosphorylated metabolites of methyl-ado were responsible for the cytotoxic activity of this compound. Methyl-ado was not a substrate for either adenosine deaminase or purine-nucleoside phosphorylase from M. smegmatis. Treatment of M. smegmatis with methyl-ado resulted in the inhibition of ATP synthesis, which indicated that a metabolite of methyl-ado inhibited one of the enzymes involved in de novo purine synthesis. These studies demonstrated the importance of adenosine kinase in the activation of methyl-ado to toxic metabolites in M. smegmatis. PMID- 11782522 TI - Bacillus amyloliquefaciens orthologue of Bacillus subtilis ywrO encodes a nitroreductase enzyme which activates the prodrug CB 1954. AB - A nitroreductase with distinct properties that can activate the prodrug 5 aziridinyl-2,4-dinitrobenzamide (CB 1954) was isolated from Bacillus amyloliquefaciens. The encoding gene was identified as a homologue of the ywrO of Bacillus subtilis, and was obtained as a PCR product by reverse genetics, cloned and the entire nucleotide sequence determined. The gene was found to reside between homologues of the B. subtilis alsD and yswB genes; however, the ywrO and yswB genes of B. amyloliquefaciens were not separated by a fourth gene, ywsA. The B. amyloliquefaciens ywrO gene was overexpressed, the recombinant protein purified and its properties were compared with those of two CB 1954-activating enzymes, Escherichia coli B nitroreductase (NTR) and Walker DT-diaphorase (DTD). In common with these enzymes menadione was an electron acceptor (K(m) 3 microM) and activity with this substrate was inhibited by the presence of dicoumarol (K(i) 1.0 microM). In contrast, YwrO showed a marked preference for NADPH as a cofactor (K(m) 40 microM) and therefore could not be classified as a DTD (EC 1.6.99.2). The flavin FMN was an acceptor with high affinity. B. amyloliquefaciens YwrO was shown to be a flavoprotein with a monomeric molecular mass of 21.5 kDa by calculation and SDS-PAGE. The cytotoxic 4-hydroxylamine derivative was the single CB 1954 reduction product, but B. amyloliquefaciens YwrO was inactive with the bischloroethyl analogue of CB 1954, SN 23862. In both of these properties B. amyloliquefaciens YwrO more closely resembles DTD than NTR. Its K(m) for CB 1954 was lower than that of NTR (617 microM compared to 862 microM). Enhanced in vitro cytotoxicity of CB 1954 was demonstrated on incubation of V79 cells with prodrug, NADPH and B. amyloliquefaciens YwrO. The work has led to the identification of a previously unknown nitroreductase, B. amyloliquefaciens YwrO, with distinct properties which will aid the rational selection of appropriate genes for applications in directed enzyme prodrug therapy (DEPT). PMID- 11782523 TI - Killing of spores of Bacillus subtilis by peroxynitrite appears to be caused by membrane damage. AB - During an infection of a higher eukaryote, dormant spores of a Bacillus species have been previously shown to be present in cells that can generate the toxic agent peroxynitrite (PON). Dormant spores of Bacillus subtilis were much more resistant to killing by PON than were growing cells, and spore-coat alteration or removal greatly decreased PON resistance. Spores were not killed by PON through DNA damage and lost no dipicolinic acid (DPA) during PON treatment. However, PON killed spores lost DPA during subsequent heat treatments that caused much less DPA release from untreated spores. Although dead, the PON-killed spores germinated and initiated metabolism but never went through outgrowth; the great majority of germinated PON-killed spores also took up propidium iodide, indicating that they had suffered significant membrane damage and were dead. Together these data suggest that spore killing by PON is through some type of damage to the spore's inner membrane. PMID- 11782524 TI - Establishment of a functional symbiosis between the cyanobacterium Nostoc punctiforme and the bryophyte Anthoceros punctatus requires genes involved in nitrogen control and initiation of heterocyst differentiation. AB - Three mutant strains (ntcA, hetR, hetF) of the cyanobacterium Nostoc punctiforme unable to differentiate heterocysts were characterized and examined for their ability to form a symbiotic association with the bryophyte Anthoceros punctatus. Previously unknown characteristics of the N. punctiforme hetR mutant include differentiation of chilling-resistant akinetes, while vegetative cells of the ntcA mutant randomly lysed, yielding short filaments, following ammonium deprivation. Strains with mutations in hetF and hetR infected A. punctatus with similar frequency to that of wild-type N. punctiforme but did not support growth of the plant partner. These results confirm that the infection of A. punctatus by hormogonia leading to the establishment of an association is physiologically uncoupled from the development of a functional diazotrophic association. They also indicate that heterocyst regulatory elements downstream from HetR and HetF are required in both free-living and symbiotic heterocyst differentiation and nitrogenase expression. A strain with a mutation in the global nitrogen regulator ntcA did not infect A. punctatus despite its ability to differentiate hormogonia at a low frequency. When complemented with one or more copies of ntcA, the mutant strain infected A. punctatus at a similar frequency as the wild-type and supported growth of the plant partner in the absence of combined nitrogen. These results established a connection between the presence of a functional copy of ntcA and the magnitude of hormogonium differentiation, and the behaviour of the formed hormogonia. PMID- 11782525 TI - NAD(P)H regeneration is the key for heterolactic fermentation of hexoses in Oenococcus oeni. AB - Oenococcus oeni (formerly Leuconostoc oenos) can perform malolactic fermentation, converting L-malate to L-lactate and carbon dioxide, in wines. The energy and redox potential required to support the growth of the micro-organism are supplied mainly by the consumption of carbohydrates via the heterolactic pathway. In the first steps of hexose metabolism two molecules of NAD(P)(+) are consumed, which must be regenerated in later reactions. The aim of this work was to test if aerobic growth of O. oeni promotes higher cell yields than anaerobic conditions, as has been shown for other lactic acid bacteria. O. oeni M42 was found to grow poorly under aerobic conditions with glucose as the only carbohydrate in the medium. It was demonstrated that O(2) inactivates the enzymes of the ethanol forming pathway, one of the two pathways which reoxidizes NAD(P)(+) cofactors in the heterolactic catabolism of glucose. These results suggest that the regeneration of cofactors is the limiting factor for the aerobic consumption of glucose. When external electron acceptors, such as fructose or pyruvate, were added to glucose-containing culture medium the growth of O. oeni was stimulated slightly; fructose was converted to mannitol, oxidizing two molecules of NAD(P)H, and pyruvate was transformed to lactate, enabling the regeneration of NAD(+). The addition of cysteine seemed to suppress the inactivation of the ethanol-forming pathway enzymes by O(2), enabling glucose consumption in aerobic conditions to reach similar rates to those found in anaerobic conditions. PMID- 11782526 TI - Methanol and acriflavine resistance in Dictyostelium are caused by loss of catalase. AB - Various chemicals with harmful effects are not themselves toxic, but are metabolized in vivo to produce toxic products. One example is methanol in Dictyostelium, which is lethal to cells containing the acrA gene, but relatively harmless to acrA mutants. This makes methanol resistance one of the tightest genetic selections in DICTYOSTELIUM: Loss of acrA also confers cross-resistance to unrelated compounds such as acriflavine and thiabendazole. We have used insertional mutagenesis to demonstrate that the acrA locus encodes the peroxisomal catalase A enzyme. Disruption of the catA gene results in parallel resistance to acriflavine. Molecular and biochemical studies of several previously characterized methanol-resistant strains reveal that each lacks catalase activity. One allele, acrA2, contains a 13 bp deletion which introduces a frameshift in the middle of the gene. The involvement of catalase in methanol resistance in Dictyostelium compares with its role in methanol metabolism in yeast and rodents. However, this is the first study to show that catalase is required for the toxicity of acriflavine. Our results imply that acriflavine and thiabendazole are precursors which must be oxidized to generate biologically active species. The catA/acrA gene is also a potentially invaluable negative selectable marker for Dictyostelium molecular genetics. PMID- 11782527 TI - Archaeal dUTPase enhances PCR amplifications with archaeal DNA polymerases by preventing dUTP incorporation. AB - We discovered a thermostable enzyme from the archaeon Pyrococcus furiosus (Pfu), which increases yields of PCR product amplified with Pfu DNA polymerase. A high molecular mass (>250 kDa) complex with PCR-enhancing activity was purified from Pfu extracts. The complex is a multimer of two discrete proteins, P45 and P50, with significant similarity to bacterial dCTP deaminase/dUTPase and DNA flavoprotein, respectively. When tested in PCR, only recombinant P45 exhibited enhancing activity. P45 was shown to function as a dUTPase, converting dUTP to dUMP and inorganic pyrophosphate. Pfu dUTPase improves the yield of products amplified with Pfu DNA polymerase by preventing dUTP incorporation and subsequent inhibition of the polymerase by dU-containing DNA. dUTP was found to accumulate during PCR through dCTP deamination and to limit the efficiency of PCRs carried out with archaeal DNA polymerases. In the absence of dUTP inhibition, the combination of cloned Pfu DNA polymerase and Pfu dUTPase (PfuTurbo DNA polymerase) can amplify longer targets in higher yield than Taq DNA polymerase. In vivo, archaeal dUTPases may play an essential role in preventing dUTP incorporation and inhibition of DNA synthesis by family B DNA polymerases. PMID- 11782528 TI - Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides. AB - Here we present a combinatorial approach to evolve a stable beta-hairpin fold in a linear peptide. Starting with a de novo-designed linear peptide that shows a beta-hairpin structure population of around 30%, we selected four positions to build up a combinatorial library of 20(4) sequences. Deconvolution of the library using circular dichroism reduced such a sequence complexity to 36 defined sequences. Circular dichroism and NMR of these peptides resulted in the identification of two linear 14-aa-long peptides that in plain buffered solutions showed a percentage of beta-hairpin structure higher than 70%. Our results show how combinatorial approaches can be used to obtain highly structured peptide sequences that could be used as templates in which functionality can be introduced. PMID- 11782529 TI - Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase. AB - The genetic code is established by the aminoacylation reactions of tRNA synthetases. Its accuracy depends on editing reactions that prevent amino acids from being assigned to incorrect codons. A group of class I synthetases share a common insertion that encodes a distinct site for editing that is about 30 A from the active site. Both misactivated aminoacyl adenylates and mischarged amino acids attached to tRNA are translocated to this site, which, in turn, is divided into subsites--one for the adenylate and one for the aminoacyl moiety attached to tRNA. Here we report that a specific mutation in isoleucyl-tRNA synthetase prevents editing by blocking translocation. The mutation alters a widely conserved residue that is believed to tether the amino group of mischarged tRNA to its subsite for editing. These and other data support a model where editing is initiated by translocation of the misacylated amino acid attached to tRNA to create an "editing complex" that facilitates subsequent rounds of editing by translocation of the misactivated adenylate. PMID- 11782530 TI - Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice. AB - Susceptibility of activated T cells to apoptosis must be tightly regulated to ensure sufficient T cell progeny for an effective response, while allowing a rapid depletion of them at the end of the immune response. We show here that a previously isolated, NF-kappa B/rel target gene IEX-1 (Immediate Early response gene X-1) is highly expressed in T cells at early stages of activation, but declines with a prolonged period of activation time, coincident with an increased susceptibility of T cells to apoptosis during the late phases of an immune response. Transgenic expression of IEX-1 specifically in lymphocytes impaired apoptosis in activated T cells, extended a duration of an effector-phase of a specific immune response, and increased the accumulation of effector/memory-like T cells and the susceptibility to a lupus-like autoimmune disease. Our study demonstrated an antiapoptotic effect of IEX-1 on T cell apoptosis triggered by ligation of Fas and T cell receptor (TCR)/CD3 complex. The ability of extending life expectancy of T effectors, in line with a decrease in its expression following prolonged T cell activation, suggests a key role for IEX-1 in regulating T cell homeostasis during immune responses. PMID- 11782531 TI - Transcription-coupled repair in RNA polymerase I-transcribed genes of yeast. AB - Nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers (CPDs) was measured in the individual strands of transcriptionally active and inactive ribosomal genes of yeast. Ribosomal genes (rDNA) are present in multiple copies, but only a fraction of them is actively transcribed. Restriction enzyme digestion was used to specifically release the transcriptionally active fraction from yeast nuclei, and selective psoralen crosslinking was used to distinguish between active and inactive rDNA chromatin. Removal of CPDs was followed in both rDNA populations, and the data clearly show that strand-specific repair occurs in transcriptionally active rDNA while being absent in the inactive rDNA fraction. Thus, transcription-coupled repair occurs in RNA polymerase I-transcribed genes in yeast. Moreover, the nontranscribed strand of active rDNA is repaired faster than either strand of inactive rDNA, implying that NER has preferred access to the active, non-nucleosomal rDNA chromatin. Finally, restriction enzyme accessibility to active rDNA varies during NER, suggesting that there is a change in ribosomal gene chromatin structure during or soon after CPD removal. PMID- 11782532 TI - Suppressors of transcriptional transgenic silencing in Chlamydomonas are sensitive to DNA-damaging agents and reactivate transposable elements. AB - In the unicellular green alga Chlamydomonas reinhardtii, the epigenetic silencing of transgenes occurs, as in land plants, at both the transcriptional and posttranscriptional levels. In the case of single-copy transgenes, transcriptional silencing takes place without detectable cytosine methylation of the introduced DNA. We have isolated two mutant strains, Mut-9 and Mut-11, that reactivate expression of a transcriptionally silenced single-copy transgene. These suppressors are deficient in the repression of a DNA transposon and a retrotransposon-like element. In addition, the mutants show enhanced sensitivity to DNA-damaging agents, particularly radiomimetic chemicals inducing DNA double strand breaks. All of these phenotypes are much more prominent in a double mutant strain. These observations suggest that multiple partly redundant epigenetic mechanisms are involved in the repression of transgenes and transposons in eukaryotes, presumably as components of a system that evolved to preserve genomic stability. Our results also raise the possibility of mechanistic connections between epigenetic transcriptional silencing and DNA double-strand break repair. PMID- 11782533 TI - Improved recognition of native-like protein structures using a family of designed sequences. AB - The goal of the inverse protein folding problem is to identify amino acid sequences that stabilize a given target protein conformation. Methods that attempt to solve this problem have proven useful for protein sequence design. Here we show that the same methods can provide valuable information for protein fold recognition and for ab initio protein structure prediction. We present a measure of the compatibility of a test sequence with a target model structure, based on computational protein design. The model structure is used as input to design a family of low free energy sequences, and these sequences are compared with the test sequence by using a metric in sequence space based on nearest neighbor connectivity. We find that this measure is able to recognize the native fold of a myoglobin sequence among different globin folds. It is also powerful enough to recognize near-native protein structures among non-native models. PMID- 11782534 TI - Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. AB - Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. ES cell-derived DA neurons caused gradual and sustained behavioral restoration of DA-mediated motor asymmetry. Behavioral recovery paralleled in vivo positron emission tomography and functional magnetic resonance imaging data demonstrating DA-mediated hemodynamic changes in the striatum and associated brain circuitry. These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease. PMID- 11782535 TI - Implications of CD94 deficiency and monoallelic NKG2A expression for natural killer cell development and repertoire formation. AB - Natural killer (NK) cells are believed to achieve self-tolerance through the expression of self-MHC-specific inhibitory receptors, such as members of the Ly49 and CD94/NKG2 families. Individual Ly49 genes are stochastically expressed by NK subsets and are expressed in a monoallelic fashion, but little is known about the mechanisms underlying CD94/NKG2A expression. We show here that, like Ly49 genes, mouse Nkg2a is stochastically and monoallelically expressed. Thus, a single general mechanism controls expression of all known MHC-specific receptors by mouse NK cells. In addition, we find that DBA/2J mice are naturally CD94 deficient and do not express cell-surface CD94/NKG2A receptors, even on neonatal NK cells. Thus, self-tolerance of neonatal NK cells cannot be attributed to CD94/NKG2A expression. Taken together, the results lead to a reconsideration of current models of NK cell development and self-tolerance. PMID- 11782536 TI - tRNA elements mediate the assembly of an icosahedral RNA virus. AB - tRNAs, the adapter molecules in protein synthesis, also serve as metabolic cofactors and as primers for viral RNA-directed DNA synthesis. The genomic and subgenomic RNAs of some plant viruses have a 3'-terminal tRNA-like structure (TLS) that can accept a specific amino acid and serve as a site for initiation of replication and as a simple telomere. We report a previously undescribed role for the TLS of brome mosaic virus (BMV), and potentially for cellular tRNA, in mediating the assembly of its icosahedral virions. BMV genomic RNAs and subgenomic RNA lacking the TLS failed to assemble into virions when incubated with purified BMV coat protein. Assembly was restored by addition of a 201-nt RNA containing the BMV TLS. TLSs from two other plant viruses as well as tRNAs from wheat germ and yeast were similarly active in the BMV virion assembly reaction, but ribosomal RNA and polyadenylate did not facilitate assembly. Surprisingly, virions assembled from TLS-less BMV RNA in the presence of tRNAs or TLS containing short RNA did not incorporate the latter molecules. Consistent with a critical role for the BMV TLS in virion assembly, mutations in the BMV genomic RNAs that were designed to disrupt the folding of the TLS also abolished virion assembly. We discuss the likely roles of the TLS in early stages of virion assembly. PMID- 11782537 TI - Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1). AB - Mice with inactivation of the gene encoding the suppressor of cytokine signaling 1 (SOCS-1) die in neonatal life with an IFN-gamma-dependent inflammatory disease dominated by fatty degeneration and necrosis of the liver. To establish the long term pathological consequences of loss of SOCS-1 in mice, where initial survival was made possible by also deleting the IFN-gamma gene, a comparison was made of the lifespan of groups of SOCS-1(-/-) IFN-gamma(-/-), SOCS-1(+/+) IFN-gamma(-/-) and SOCS-1(+/+) IFN-gamma(+/+) mice. Mice lacking the genes for both SOCS-1 and IFN-gamma exhibited an accelerated death rate compared with control groups. Disease states developing selectively in SOCS-1(-/-) IFN-gamma(-/-) mice were polycystic kidneys, pneumonia, chronic skin ulcers, and chronic granulomas in the gut and various other organs. Mice of all three groups developed cataracts, but disease development was accelerated in the groups lacking IFN-gamma. SOCS-1(-/-) IFN-gamma(-/-) mice exhibited a slightly increased predisposition to the development of T lymphoid leukemia, either spontaneous or radiation-induced. The development of polycystic kidneys may be caused by a developmental defect in renal-tubule organization noted in neonatal SOCS-1(-/-) mice. The chronic infections and granulomas of SOCS-1(-/-) IFN-gamma(-/-) mice may be based on autoaggression of SOCS-1(-/-) T lymphoid and related cells or a functional deficiency of these cells when lacking SOCS-1. PMID- 11782538 TI - Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. AB - Hemoglobin degradation is a metabolic process that is central to the growth and maturation of the malaria parasite Plasmodium falciparum. Two aspartic proteases that initiate degradation, plasmepsins (PMs) I and II, have been identified and extensively characterized. Eight additional PM genes are present in the P. falciparum genome. To better understand the enzymology of hemoglobin degradation, it is necessary to determine which of these genes are expressed when hemoglobin degradation is occurring, which encode active enzymes, and which gene products are found in the food vacuole where catabolism takes place. Our genome-wide analysis reveals that PM I, II, and IV and histo-aspartic protease encode hemoglobin-degrading food vacuole proteases. Despite having a histidine in place of one of the catalytic aspartic acids conserved in other aspartic proteases, histo-aspartic protease is an active hydrolase. PMID- 11782539 TI - Activated glycogen synthase-3 beta suppresses cardiac hypertrophy in vivo. AB - The adult myocardium responds to a variety of pathologic stimuli by hypertrophic growth that frequently progresses to heart failure. The calcium/calmodulin dependent protein phosphatase calcineurin is a potent transducer of hypertrophic stimuli. Calcineurin dephosphorylates members of the nuclear factor of activated T cell (NFAT) family of transcription factors, which results in their translocation to the nucleus and activation of calcium-dependent genes. Glycogen synthase kinase-3 (GSK-3) phosphorylates NFAT proteins and antagonizes the actions of calcineurin by stimulating NFAT nuclear export. To determine whether activated GSK-3 can act as an antagonist of hypertrophic signaling in the adult heart in vivo, we generated transgenic mice that express a constitutively active form of GSK-3 beta under control of a cardiac-specific promoter. These mice were physiologically normal under nonstressed conditions, but their ability to mount a hypertrophic response to calcineurin activation was severely impaired. Similarly, cardiac-specific expression of activated GSK-3 beta diminished hypertrophy in response to chronic beta-adrenergic stimulation and pressure overload. These findings reveal a role for GSK-3 beta as an inhibitor of hypertrophic signaling in the intact myocardium and suggest that elevation of cardiac GSK-3 beta activity may provide clinical benefit in the treatment of pathologic hypertrophy and heart failure. PMID- 11782540 TI - A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants. AB - Conformationally compromised oncogenic mutants of the tumor suppressor protein p53 can, in principle, be rescued by small molecules that bind the native, but not the denatured state. We describe a strategy for the rational search for such molecules. A nine-residue peptide, CDB3, which was derived from a p53 binding protein, binds to p53 core domain and stabilizes it in vitro. NMR studies showed that CDB3 bound to p53 at the edge of the DNA binding site, partly overlapping it. The fluorescein-labeled peptide, FL-CDB3, binds wild-type p53 core domain with a dissociation constant of 0.5 microM, and raises the apparent melting temperatures of wild-type and a representative oncogenic mutant, R249S core domain. gadd45 DNA competes with CDB3 and displaces it from its binding site. But this competition does not preclude CDB3 from being a lead compound. CDB3 may act as a "chaperone" that maintains existing or newly synthesized destabilized p53 mutants in a native conformation and then allows transfer to specific DNA, which binds more tightly. Indeed, CDB3 restored specific DNA binding activity to a highly destabilized mutant I195T to close to that of wild-type level. PMID- 11782541 TI - Brucella melitensis: a nasty bug with hidden credentials for virulence. PMID- 11782542 TI - Structured intermittent treatment for HIV disease: Necessary concession or premature compromise? PMID- 11782543 TI - Bacterial chemotaxis and the question of gain. PMID- 11782544 TI - In our genes. PMID- 11782546 TI - The large GTPase dynamin regulates actin comet formation and movement in living cells. AB - The large GTPase dynamin (Dyn2) has been demonstrated by us and others to interact with several different actin-binding proteins. To define how Dyn2 might participate in actin dynamics in livings cells we have expressed green fluorescent protein (GFP)-tagged Dyn2 in cultured cells and observed labeling of comet-like vesicles and macropinosomes. The comet structures progressed with a constant velocity and were reminiscent of actin comets associated with motile vesicles in cells expressing type I phosphatidylinositol phosphate 5-kinases. Based on these observations we sought to determine whether Dyn2 is an integral component of actin comets. Cells expressing type I phosphatidylinositol phosphate 5-kinase and Dyn2-GFP revealed a prominent colocalization of Dyn2 and actin in comet structures. Interestingly, comet formation and motility were normal in cells expressing wild-type Dyn2-GFP but altered markedly in Dyn2 mutant expressing cells. Dyn2K44A-GFP mutant cells displayed a significant reduction in comet number, length, velocity, and efficiency of movement. In contrast, comets in cells expressing Dyn2DeltaPRD-GFP appeared dark and did not incorporate the mutant Dyn2 protein, indicating that the proline-rich domain (PRD) is required for Dyn2 recruitment. Further, these comets were significantly longer and slower than those in control cells. These findings demonstrate a role for Dyn2 in actin based vesicle motility. PMID- 11782547 TI - Translocation of Cockayne syndrome group A protein to the nuclear matrix: possible relevance to transcription-coupled DNA repair. AB - Transcription-coupled repair (TCR) efficiently removes a variety of lesions from the transcribed strand of active genes. By allowing rapid resumption of RNA synthesis, the process is of major importance for cellular resistance to transcription-blocking genotoxic damage. Mutations in the Cockayne syndrome group A or B (CSA or CSB) gene result in defective TCR. However, the exact mechanism of TCR in mammalian cells remains to be elucidated. We found that CSA protein is rapidly translocated to the nuclear matrix after UV irradiation. The translocation of CSA was independent of Xeroderma pigmentosum group C, which is specific to the global genome repair subpathway of nucleotide excision repair (NER) and of the core NER factor Xeroderma pigmentosum group A but required the CSB protein. In UV-irradiated cells, CSA protein colocalized with the hyperphosphorylated form of RNA polymerase II, engaged in transcription elongation. The translocation of CSA was also induced by treatment of the cells with cisplatin or hydrogen peroxide, both of which produce damage that is subjected to TCR but not induced by treatment with dimethyl sulfate, which produces damage that is not subjected to TCR. The hydrogen peroxide-induced translocation of CSA was also CSB dependent. These findings establish a link between TCR and the nuclear matrix mediated by CSA. PMID- 11782545 TI - Dynamin at actin tails. AB - Dynamin, the product of the shibire gene of Drosophila, is a GTPase critically required for endocytosis. Some studies have suggested a functional link between dynamin and the actin cytoskeleton. This link is of special interest, because there is evidence implicating actin dynamics in endocytosis. Here we show that endogenous dynamin 2, as well as green fluorescence protein fusion proteins of both dynamin 1 and 2, is present in actin comets generated by Listeria or by type I PIP kinase (PIPK) overexpression. In PIPK-induced tails, dynamin is further enriched at the interface between the tails and the moving organelles. Dynamin mutants harboring mutations in the GTPase domain inhibited nucleation of actin tails induced by PIPK and moderately reduced their speed. Although dynamin localization to the tails required its proline-rich domain, expression of a dynamin mutant lacking this domain also diminished tail formation. In addition, this mutant disrupted a membrane-associated actin scaffold (podosome rosette) previously shown to include dynamin. These findings suggest that dynamin is part of a protein network that controls nucleation of actin from membranes. At endocytic sites, dynamin may couple the fission reaction to the polymerization of an actin pool that functions in the separation of the endocytic vesicles from the plasma membrane. PMID- 11782548 TI - A role for biliverdin IXalpha in dorsal axis development of Xenopus laevis embryos. AB - The determinants of Xenopus laevis embryos that act before their first cell division are mandatory for the formation of mRNas required to establish the dorsal axis. Although their chemical identities are unknown, a number of their properties have long been recognized. One of the determinants is present in the cytoplasm and is sensitive to UV light. Thus, exposing stage 1 embryos to either standard 254-nm or, as shown here, to 366-nm UV light during the 0.3-0.4 time fraction of their first cycle inactivates the cytoplasmic determinant. As a consequence, both types of irradiated embryos fail to express dorsal markers, e.g., goosecoid and chordin, without affecting formation of ventral markers, e.g., Vent-1. The developmental outcome is dorsal axis-deficient morphology. We report here that biliverdin IXalpha, a normal constituent of cytoplasmic yolk platelets, is photo-transformed by irradiation with either 254- or 366-nm UV light and that the transformation triggers the dorsal axis deficiency. When the 254- or 366-nm UV-irradiated embryos, fated to dorsal axis deficiency, are incubated solely with microM amounts of biliverdin, they recover and form the axis. In contrast, incubation with either in vitro photo-transformed biliverdin or biliverdin IXalpha dimethyl ester does not induce recovery. The results define an approach to produce dorsal axis-deficient embryos by photo-transforming its biliverdin by irradiation with 366-nm UV light and identify an unsuspected role for biliverdin IXalpha in X. laevis embryogenesis. PMID- 11782549 TI - Disappearance of insectivorous birds from tropical forest fragments. AB - Determining the impact of forest disturbance and fragmentation on tropical biotas is a central goal of conservation biology. Among tropical forest birds, understory insectivores are particularly sensitive to habitat disturbance and fragmentation, despite their relatively small sizes and freedom from hunting pressure. Why these birds are especially vulnerable to fragmentation is not known. Our data indicate that the best determinant of the persistence of understory insectivorous birds in small fragments is the ability to disperse through deforested countryside habitats. This finding contradicts our initial hypothesis that the decline of insectivorous birds in forest fragments is caused by impoverished invertebrate prey base in fragments. Although we observed significantly fewer insectivorous birds in smaller fragments, extensive sampling of invertebrate communities (106,082 individuals) and avian diets (of 735 birds) revealed no important differences between large and small fragments. Neither habitat specificity nor drier fragment microclimates seemed critical. Bird species that were less affected by forest fragmentation were, in general, those that used the deforested countryside more, and we suggest that the key to their conservation will be found there. PMID- 11782550 TI - Evolution of sociality in a primitively eusocial lineage of bees. AB - Eusociality is a major evolutionary innovation involving alterations in life history, morphology, and behavior. Advanced eusocial insects, such as ants, termites, and corbiculate bees, cannot provide insights into the earliest stages of eusocial evolution because eusociality in these taxa evolved long ago (in the Cretaceous) and close solitary relatives are no longer extant. In contrast, primitively eusocial insects, such as halictid bees, provide insights into the early stages of eusocial evolution because eusociality has arisen recently and repeatedly. By mapping social behavior onto well-corroborated phylogenies, I show that eusociality has arisen only three times within halictid bees (contrary to earlier estimates of six or more origins). Reversals from eusocial to solitary behavior have occurred as many as 12 times, indicating that social reversals are common in the earliest stages of eusocial evolution. Important attributes of social complexity (e.g., colony size, queen/worker dimorphism) show no obvious association with phylogeny, and some reversals to solitary nesting are related to host-plant switches (from polylecty to oligolecty). These results provide a glimpse of social evolution in its earliest stages and provide insights into the early evolution of advanced eusocial organisms. PMID- 11782551 TI - Amino acid runs in eukaryotic proteomes and disease associations. AB - We present a comparative proteome analysis of the five complete eukaryotic genomes (human, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana), focusing on individual and multiple amino acid runs, charge and hydrophobic runs. We found that human proteins with multiple long runs are often associated with diseases; these include long glutamine runs that induce neurological disorders, various cancers, categories of leukemias (mostly involving chromosomal translocations), and an abundance of Ca(2 +) and K(+) channel proteins. Many human proteins with multiple runs function in development and/or transcription regulation and are Drosophila homeotic homologs. A large number of these proteins are expressed in the nervous system. More than 80% of Drosophila proteins with multiple runs seem to function in transcription regulation. The most frequent amino acid runs in Drosophila sequences occur for glutamine, alanine, and serine, whereas human sequences highlight glutamate, proline, and leucine. The most frequent runs in yeast are of serine, glutamine, and acidic residues. Compared with the other eukaryotic proteomes, amino acid runs are significantly more abundant in the fly. This finding might be interpreted in terms of innate differences in DNA-replication processes, repair mechanisms, DNA-modification systems, and mutational biases. There are striking differences in amino acid runs for glutamine, asparagine, and leucine among the five proteomes. PMID- 11782553 TI - Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. AB - Over the past decade xenotransplantation systems have been used with increasing success to gain a better understanding of human cells that are able to initiate and maintain the hematopoietic system in vivo. The nonobese diabetic/severe combined immunodeficiency (SCID) mouse has been a particularly useful model. Human cells capable of hematopoietic repopulation in this mouse, termed SCID repopulating cells, have been assumed to represent the most primitive elements of the hematopoietic system, responsible for long-term maintenance of hematopoiesis. However, we demonstrate that SCID-repopulating cells present in the CD34(+) cell fraction of cord blood can be segregated into subpopulations with distinct repopulation characteristics. CD34(+)/CD38(+) progenitors can repopulate recipients rapidly, but can only maintain the graft for 12 weeks or less and have no secondary repopulation potential. Conversely, the more primitive CD34(+)/CD38( ) subpopulation repopulates recipients more gradually, can maintain the graft for at least 20 weeks, and contains cells with serial repopulation potential throughout the engraftment period. Additionally, a much higher frequency of T cell precursors are found among SCID-repopulating cells in the CD34(+)/CD38(-) subpopulation. These findings demonstrate that cells with variable repopulation potential comprise the human CD34(+) population and that short- and long-term potential of human precursors can be evaluated in the mouse model. PMID- 11782552 TI - HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. AB - To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Delta32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor. PMID- 11782554 TI - Phylogenetic relationships among domesticated and wild species of Cucurbita (Cucurbitaceae) inferred from a mitochondrial gene: Implications for crop plant evolution and areas of origin. AB - We have investigated the phylogenetic relationships among six wild and six domesticated taxa of Cucurbita using as a marker an intron region from the mitochondrial nad1 gene. Our study represents one of the first successful uses of a mtDNA gene in resolving inter- and intraspecific taxonomic relationships in Angiosperms and yields several important insights into the origins of domesticated Cucurbita. First, our data suggest at least six independent domestication events from distinct wild ancestors. Second, Cucurbita argyrosperma likely was domesticated from a wild Mexican gourd, Cucurbita sororia, probably in the same region of southwest Mexico that gave rise to maize. Third, the wild ancestor of Cucurbita moschata is still unknown, but mtDNA data combined with other sources of information suggest that it will probably be found in lowland northern South America. Fourth, Cucurbita andreana is supported as the wild progenitor of Cucurbita maxima, but humid lowland regions of Bolivia in addition to warmer temperate zones in South America from where C. andreana was originally described should possibly be considered as an area of origin for C. maxima. Fifth, our data support other molecular results that indicate two separate domestications in the Cucurbita pepo complex. The potential zone of domestication for one of the domesticated subspecies, C. pepo subsp. ovifera, includes eastern North America and should be extended to northeastern Mexico. The wild ancestor of the other domesticated subspecies, C. pepo subsp. pepo, is undiscovered but is closely related to C. pepo subsp. fraterna and possibly will be found in southern Mexico. PMID- 11782555 TI - Toll-like receptors. AB - The ability of a host to sense invasion by pathogenic organisms and to respond appropriately to control infection is paramount to survival. In the case of sepsis and septic shock, however, an exaggerated systemic response may, in fact, contribute to the morbidity and mortality associated with overwhelming infections. The innate immune system has evolved as the first line of defense against invading microorganisms. The Toll-like receptors (TLRs) are a part of this innate immune defense, recognizing conserved patterns on microorganisms. These TLRs and their signaling pathways are represented in such diverse creatures as mammals, fruit flies, and plants. Ten members of the TLR family have been identified in humans, and several of them appear to recognize specific microbial products, including lipopolysaccharide, bacterial lipoproteins, peptidoglycan, and bacterial DNA. Signals initiated by the interaction of TLRs with specific microbial patterns direct the subsequent inflammatory response. Thus, TLR signaling represents a key component of the innate immune response to microbial infection. PMID- 11782556 TI - Carbon monoxide-dependent signaling. AB - It has become accepted that nitric oxide serves important functions in biological systems as a second messenger. Another diatomic gaseous molecule, carbon monoxide (CO), is also rapidly gaining acceptance as a signaling agent. Some of the activities of CO are analogous to those of nitric oxide in the vascular system and the brain, but CO also behaves in novel ways. Like nitric oxide, CO is capable of activating soluble guanylyl cyclase. This mechanism of CO signaling is important in vasodilation and neurotransmission. There is growing evidence, however, that CO also acts independently of soluble guanylyl cyclase. CO has been shown to protect against septic shock and lung injury in animal models, and the mitogen-activated protein kinase system appears to mediate this cytoprotective effect. Although much remains to be elucidated about the mechanisms of cell signaling by CO, the pace of discovery in this field is making the picture clearer with every passing day. PMID- 11782557 TI - The IKK/NF-kappa B pathway. PMID- 11782558 TI - Macrophage migration inhibitory factor. AB - Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF. PMID- 11782559 TI - High-mobility group-I/Y proteins: potential role in the pathophysiology of critical illnesses. AB - High-mobility group (HMG) proteins are architectural factors that have been shown to play a role in the transcriptional regulation of various mammalian genes. One family of HMG proteins, HMG-I/Y, is known to facilitate the initiation of gene transcription by modifying the conformation of DNA and recruiting transcription factors into an organized complex on transcriptional regulatory regions of specific genes. In many circumstances, the nuclear factor-kappa B family of transcription factors is involved in gene regulation that is mediated by HMG-I/Y. We will review the mechanisms by which HMG-I/Y proteins regulate gene transcription, give an overview of selected genes regulated by HMG-I/Y, summarize the potential roles of these genes in critical illnesses, and provide more detailed information about the role of HMG-I/Y in the regulation of nitric oxide synthase-2 during an inflammatory response, such as endotoxemia/sepsis. PMID- 11782560 TI - Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. AB - OBJECTIVE: Life-threatening conditions cause severe changes in the organization and conformation of macromolecules, creating urgent requirements for protein repair to ensure survival. As molecular chaperones, heat shock proteins (HSP) that have specialized functions in protein folding are now well established to restore homeostasis in cells and organisms. Augmentation of HSP synthesis is tightly regulated by stress-inducible heat shock factors (HSF), which are part of a transcriptional signaling cascade with both positive (e.g., HSP) and negative (e.g., proinflammatory cytokines) properties. In this review, we discuss the biological roles and mechanisms of HSP-mediated protection in pathophysiologic conditions (ischemia, sepsis, and preeclampsia) and the regulation for stress dependent HSP synthesis and speculate about future applications for harnessing HSF and HSP partners as cytoprotective agents. DATA SOURCES: Reactive oxygen species are major pathogenic factors in cell death pathways (e.g., necrosis, apoptosis), in part, because of proteotoxic effects. In intact organisms, forced overexpression of HSP per se affords effective counterbalance against ischemia challenges (e.g., heart and brain) and systemic conditions (e.g., sepsis). Besides stressful conditions, gene-targeting studies have uncovered new functions for heat shock transcription factors (e.g., maintenance of intrauterine pregnancy) in mammals. In parallel, pharmacologic studies using small molecules are paving the way for future prospects to exploit the beneficial properties of HSP, albeit an important but presently elusive goal. CONCLUSIONS: Together, HSF and HSP partners are attractive targets in therapeutic strategies designed to stimulate endogenous protective mechanisms against deleterious consequences of oxidative stress. With further technological advances, it is anticipated that the spotlight on HSP, alone or in combination with other stress response pathways, could, ultimately, reduce injury and accelerate functional recovery of susceptible organs in living organisms including humans. PMID- 11782561 TI - Functional genomics of critical illness and injury. PMID- 11782562 TI - Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. AB - Interleukin (IL)-10 is a pleiotropic cytokine produced by both T cells and macrophages and possesses both anti-inflammatory and immunosuppressive properties. IL-10 circulates in the blood of patients with sepsis syndromes, and increased concentrations of IL-10 have been associated with an adverse clinical outcome. Experimental studies in rodents and primates have demonstrated that endogenously produced and exogenously administered IL-10 can reduce the magnitude of the inflammatory response and improve outcome, primarily in models of endotoxemic and bacteremic shock. However, endogenous IL-10 production and systemic administration can also exacerbate T-cell dysfunction, decrease T-cell apoptosis, reduce antimicrobial function, and increase mortality in other less acute bacterial models of sepsis or after thermal injury. Targeted delivery of IL 10 to individual tissues may obviate the adverse effects of systemic delivery. The potential anti-inflammatory properties of IL-10 will have to be carefully weighed against its immunosuppressive properties when considering its use in patients with acute inflammation and sepsis syndromes. PMID- 11782563 TI - Endotoxin tolerance: a review. AB - Endotoxin tolerance was initially described when it was observed that animals survived a lethal dose of bacterial endotoxin if they had been previously treated with a sublethal injection. In animal models, two phases of endotoxin tolerance are described, an early phase associated with altered cellular activation and a late phase associated with the development of specific antibodies against the polysaccharide side chain of Gram-negative organisms. Recently, there has been a tremendous resurgence of interest in the mechanisms responsible for altered responsiveness to bacterial endotoxin. Host immune cells, particularly macrophages and monocytes, that are exposed to endotoxin for 3 to 24 hrs are rendered "tolerant" and manifest a profoundly altered response when rechallenged with bacterial endotoxin or lipopolysaccharide. The "lipopolysaccharide-tolerant" phenotype is characterized by inhibition of lipopolysaccharide-stimulated tumor necrosis factor production, altered interleukin-1 and interleukin-6 release, enhanced cyclooxygenase-2 activation, inhibition of mitogen-activated protein kinase activation, and impaired nuclear factor-kappa B translocation. Human monocytes and macrophages can be induced to become tolerant, and there is increasing evidence that monocytic cells from patients with systemic inflammatory response syndrome and sepsis have many characteristics of endotoxin tolerance. PMID- 11782564 TI - Mitogen-activated protein kinases. AB - The cellular control switches are regulated through an extensive network of interactive intracellular signal transduction pathways, such as the mitogen activated protein kinase (MAPK) family. The MAPK pathways may play an important role in the inappropriate inflammatory responses that lead to systemic inflammatory response syndrome or multiple organ dysfunction syndrome. Therefore, elucidating the activation status of the MAPK pathways may be a method to identify patients at risk for systemic inflammatory response syndrome/multiple organ dysfunction syndrome. Also, manipulating the proper pathways may improve patients' outcomes. However, the MAPK family is part of a complex interactive network, which may initiate an unpredictable reaction to the indiscriminate inhibition or activation of a single component. A major challenge is to elucidate the principles by which the network is assembled, so a more tissue- and temporal specific approach can be used. PMID- 11782565 TI - Phosphatases: counterregulatory role in inflammatory cell signaling. AB - Cellular responses to external stimuli proceed through multiply complex signal transduction networks. The manner by which signals are propagated from the cell's surface to the nuclei is, in large part, dependent on the phosphorylation of signaling proteins mediated by kinases. As in most biological systems, this process of kinase-mediated phosphorylation is balanced by the presence of a dephosphorylating system comprised of a number of families of phosphatases. The purpose of this review is to describe the various members of the main classes of phosphatases and to examine their role in regulating signal transduction pathways relevant to critical illness. Because recent work has provided key insight into the role of kinase-mediated signaling pathways, such as the mitogen-activated protein kinase and inhibitor of nuclear factor-kappa B kinase pathways, in inflammatory states, emphasis has been placed on the regulation of these events. It is hoped that deriving novel insight into the regulatory phosphatases will allow a greater understanding of inflammatory cell signaling events and potentially identify novel sites for therapeutic intervention in the future. PMID- 11782566 TI - Interactions between the heat shock response and the nuclear factor-kappa B signaling pathway. AB - The heat shock response (HSR) and the nuclear factor (NF)-kappa B signaling pathway are two fundamental cellular responses. Various laboratories have documented in vitro and in vivo interactions between the HSR and NF-kappa B activation when they are activated sequentially. For example, induction of the HSR before a proinflammatory signal inhibits NF-kappa B activation and NF-kappa B dependent proinflammatory gene expression. The central point of control appears to be at the level of I kappa B alpha phosphorylation as demonstrated by HSR mediated inhibition of I kappa B kinase activation and HSR-mediated induction of intracellular phosphatase activity. In addition, induction of the HSR can independently increase de novo expression of the I kappa B alpha gene, thereby providing another potential mechanism through which the HSR can modulate cellular proinflammatory signaling. Another level of interaction is illustrated by the observation that various pharmacologic inhibitors of the NF-kappa B pathway are capable of simultaneously inducing the HSR. In direct contrast, induction of the HSR after a proinflammatory signal can lead to programmed cell death. Further understanding of how these two fundamental cellular responses interact at the molecular level holds the potential to elucidate some of the molecular interactions that occur during disease states common to critical care medicine. PMID- 11782567 TI - Helicobacter pylori, NSAIDs and gastrointestinal haemorrhage. AB - Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) cause the majority of bleeding ulcers. Whether the presence of H. pylori infection would affect the risk of ulcers in patients taking NSAIDs is important for both theoretical and practical reasons. However, the results have been so conflicting that there is no consensus on the management of patients requiring NSAIDs who are infected with H. pylori. The controversy is largely due to the variable study design and marked heterogeneity of the study population. Studying the interaction between H. pylori and NSAIDs without considering these factors often leads to erroneous conclusions. Current evidence suggests that H. pylori contributes to an increased ulcer risk for patients who are about to start NSAID treatment, whereas NSAIDs probably account for the majority of ulcer disease in patients who are already taking long-term NSAIDs. In the light of the reduced gastric toxicity of COX-2 inhibitors, the relative importance of H. pylori in the pathogenesis of ulcers is expected to increase. Furthermore, recent evidence suggests that H. pylori contributes to ulcer bleeding associated with low-dose aspirin. Among H. pylori-positive patients with a history of ulcer bleeding who are taking low-dose aspirin, the eradication of H. pylori has been shown to be comparable to omeprazole in preventing recurrent bleeding. PMID- 11782568 TI - Prokinetics and reflux: a promise unfulfilled. AB - Gastro-oesophageal reflux disease (GORD) has been described as a motility disorder of the upper gastrointestinal tract. Disturbances of lower oesophageal sphincter function, lower oesophageal body motility, oesophageal clearance and gastric emptying are well accepted. Cisapride improves most of these but its clinical benefits have been relatively modest. Some recent studies have indicated that the improvements achieved with cisapride may be less marked than originally thought. Furthermore, the agent has no effect on transient lower oesophageal sphincter relaxations, nor on other important factors influencing gastro oesophageal junction competence, such as the external sphincter function of the diaphragmatic crus and mechanical influences such as lower oesophageal sphincter length exposed to intra-abdominal pressure changes. More potent, specific and predictable prokinetic agents would be welcome, but are unlikely to be effective as single agents across the range of GORD. There is certainly a need for such agents, including cisapride, as adjuncts to acid suppression in patients who fail to respond to the latter. PMID- 11782569 TI - The effect of cisapride on oesophageal motility and lower sphincter function in patients with gastro-oesophageal reflux disease. AB - OBJECTIVES: To evaluate the efficiency by which the 5-HT4 agonist cisapride affects important motor functions involved in the control of gastro-oesophageal reflux. METHOD: Thirty patients with proven gastro-oesophageal reflux disease (endoscopy and 24 h pH-metry) were included in a randomized, double-blind, placebo controlled study with a cross-over design. Cisapride, 20 mg b.i.d., during 4 weeks was compared with placebo. At baseline, as well as after 4 and 8 weeks all patients underwent symptom assessments, sleeve manometry with concomitant oesophageal pH-monitoring and an acid clearance test. RESULTS: Despite adequate plasma levels cisapride had no significant effect on swallow induced peristaltic amplitude, duration, propagation speed, the elicitation of secondary peristalsis nor on acid clearance. Neither the basal tone of the lower oesophageal sphincter nor the number of transient lower oesophageal sphincter relaxations induced by gas distension of the stomach was affected by the administered dose of cisapride. CONCLUSION: Although cisapride has been alleged to improve symptoms as well as the oesophagitis in patients with gastro oesophageal reflux disease, we found the compound (20 mg b.i.d.) devoid of effects on important motor mechanisms involved in the pathogenesis of the disease. PMID- 11782570 TI - Infrequent p16/CDKN2 alterations in squamous cell carcinoma of the oesophagus. AB - Loss of heterozygosity (LOH) on chromosome 9 and p16 (MTS1/CDKN2) gene mutations have been reported in various human cancers. The present study aimed to determine the prevalence of LOH in 100 oesophageal squamous cell carcinomas (OSCCs) by typing microsatellite loci and mutations of the p16 gene. The methods used included denaturing gradient gel electrophoresis (DGGE) and DNA sequencing of exon 2. LOH was found in 14.7% of the OSCC cases. Six gene alterations were identified in exon 2. They consisted of three deletions and the same polymorphism in three samples. The relatively low rate of p16 mutation compared with the frequency of LOH suggests the possible involvement of another tumour suppressor gene located on chromosome 9 in oesophageal carcinogenesis. PMID- 11782571 TI - Transjugular liver biopsy with an automated trucut-type needle: comparative study with percutaneous liver biopsy. AB - OBJECTIVE: Transjugular liver biopsy using the suction method usually produces small specimens with excessive fragmentation, hence the diagnosis adequacy of specimens and the clinical impact of performing the biopsy have been questioned. An alternative biopsy needle, the Quick-Core needle system, which uses an automated trucut-type mechanism, has been shown to produce non-fragmented tissue specimens. The aim of the present study was to evaluate the safety, adequacy and clinical impact of the transjugular liver biopsy by comparing it with the standard percutaneous liver biopsy. DESIGN: We recruited all patients who underwent liver biopsies by percutaneous or transjugular routes in the Department of Medicine, Princess Margaret Hospital, Hong Kong between January 1998 and December 1999. METHOD: We recorded demographics and clinical features of patients, indications and complications, and the clinical impact of the liver biopsy procedure. All liver biopsy specimens were reviewed by the histopathologist, who was blinded to the approach of taking the biopsy. All variables between patients undergoing transjugular and percutaneous liver biopsies were compared. RESULTS: During the study period, 50 percutaneous and 18 transjugular liver biopsies were performed. All transjugular liver biopsies were performed successfully with adequate tissue for diagnosis. Although specimens obtained by the transjugular technique tended to be shorter (10 mm v. 18 mm by the percutaneous approach, P < 0.001), the presence of fragmentation was similar to that in biopsies obtained by the percutaneous approach. Respectively, 100% and 98% of specimens obtained by the transjugular and percutaneous approaches were considered to be adequate for histological assessment. The clinical impact of transjugular and percutaneous liver procedures was comparable (89% v. 76%, P = 0.25). CONCLUSION: Specimens obtained by a transjugular automated trucut needle are sufficient for histological assessment, and carry clinical impact in patient management. PMID- 11782572 TI - Simulation of hepatitis C based on a mandatory reporting system. AB - OBJECTIVE: Hepatitis C is a major cause of liver disease in European countries. We aimed to assess the current and future disease burden of hepatitis C. SETTING: A representative data set of hepatitis C was applied to a validated computer model. METHODS: The mandatory reporting of positive hepatitis C virus (HCV) test results by all medical laboratories in Switzerland and the clinical data obtained by questionnaire for each positive test from the treating physicians created a unique, representative epidemiological database allowing the determination of the age distribution of acute (i.e. newly acquired) and chronic HCV infections. Based on these data and a simulation model of the natural history of hepatitis C, we estimated the prevalence of HCV infection, future morbidity/mortality from cirrhosis/hepatocellular carcinoma and costs. RESULTS: Our analysis estimates a prevalence of anti-HCV in Switzerland of 1.25-1.75%, which is slightly higher than prior reports (0.5-1%) derived by extrapolation from selected populations. Although new HCV infections decreased after 1990, our analysis predicts that HCV related morbidity and mortality will increase by 70-90%, reaching a maximum in 2015-2020, largely from complications in cases already prevalent in 1998. The model predicts that the incidence of cirrhosis will begin to decrease after 2005 2010. Antiviral treatment reduces disease burden by approximately 5%. Undiscounted HCV-related annual direct costs will more than double and reach a maximum of almost US$33 million in 2020. CONCLUSIONS: The incidence of HCV related cirrhosis is predicted to decrease after 2005-2010, while disease burden and costs due to complications are estimated to continue to increase until 2015 2020. PMID- 11782573 TI - Increased incidence of anti-LKM autoantibodies in a consecutive cohort of hepatitis C patients from central Greece. AB - OBJECTIVES: In Greece, there are insufficient data regarding the presence of non organ and liver-related autoantibodies in hepatitis C patients. This study in a consecutive cohort of 39 such patients from central Greece investigates (1) the prevalence of non-organ and liver-related autoantibodies, and (2) the reactivity of anti-liver-kidney microsomal type 1 antibodies (in the case of positivity with at least one of the methods used) against their molecularly defined antigens. DESIGN: All serum samples were tested by standard and molecular assays for the presence of anti-nuclear antibodies, smooth muscle antibodies, anti-liver-kidney microsomal type 1 antibodies, antibodies against parietal cells, anti-CYP2A6, anti-CYP1A2 and anti-CYP2D6 autoantibodies. METHODS: Indirect immunofluorescence, competitive enzyme-linked immunosorbent assays, immunoblotting and novel radioligand assays based on immunoprecipitation of [35S]-methionine labelled recombinant CYP2A6, CYP1A2 and CYP2D6 His-taq fusion proteins produced by in vitro transcription/translation were used. RESULTS: Seven out of 39 patients (17.9%) tested positive for smooth muscle antibodies, 2/39 (5.1%) tested positive for anti-nuclear antibodies, 1/39 (2.5%) tested positive for parietal cell antibodies, and 4/39 (10.3%) were found to be anti-liver-kidney microsomal positive (with at least one of the methods used). All sera were negative for anti CYP2A6 and anti-CYP1A2 autoantibodies. Three out of four anti-liver-kidney microsomal positive samples had the typical liver-kidney microsomal staining pattern shown by indirect immunofluorescence. However, none tested positive for anti-CYP2D6 autoantibodies using the competitive CYP2D6 enzyme-linked immunosorbent assay, the specific CYP2D6 radioligand assay, and western blot using either human microsomes or recombinant CYP2D6. The fourth patient tested negative for anti-liver-kidney autoantibodies by either indirect immunofluorescence or the competitive enzyme-linked immunosorbent assay, but was repeatedly positive for anti-CYP2D6 autoantibodies by the sensitive and specific radioligand assay. Western blot experiments using human microsomes in this patient serum revealed two bands of 50 kDa and 55 kDa that documented as anti CYP2D6 and anti-uridine triphosphate glucuronosyltransferase autoantibodies when recombinant CYP2D6 and recombinant uridine triphosphate glucuronosyltransferase autoantigens were used for immunoblot, respectively. CONCLUSIONS: A relatively high incidence of anti-liver-kidney microsomal autoantibodies (10.3%) was found in a consecutive sample of Greek patients with hepatitis C. The expanded panel of assays, however, failed to document CYP2D6 as the target autoantigen of anti liver-kidney microsomal autoantibodies in most patients. We report for the first time the detection of parietal cell antibodies and both anti-CYP2D6 (anti-liver kidney microsomal type 1) and anti-uridine triphosphate glucuronosyltransferase (anti-liver-kidney microsomal type 3) autoantibodies in patients who were hepatitis C positive/hepatitis D negative. Further studies are needed to confirm our findings and to determine whether these preliminary results have a clinical importance or not. PMID- 11782574 TI - Increased rate of bone loss at the femoral neck in patients with chronic liver disease. AB - OBJECTIVE: Patients with chronic liver disease (CLD) have an increased prevalence of osteoporosis. The aim of this study was to evaluate prospectively the rate of bone loss and potential predictors of increased bone loss in a cohort of patients with CLD. DESIGN: Bone mineral density (BMD) was measured at baseline and at follow-up by dual-energy X-ray absorptiometry at the lumbar spine and the femoral neck. RESULTS: Forty-three patients (31 female, 12 male) were available for a second measurement of BMD, with a median of 25 months (range 18-41) between the measurements. Mean annual bone loss at the lumbar spine and the femoral neck, respectively, was 0.6 +/- 2.0% and 1.5 +/- 2.4% in females and 0.8 +/- 1.9% and 2.9 +/- 2.0% in males. The BMD Z score decreased significantly over time at the femoral neck (P = 0.005 and P = 0.02 for females and males, respectively). Bone loss was increased significantly at the lumbar spine in patients classified as Child-Pugh B + C compared with those classified as Child-Pugh A (P = 0.04). Serum levels of bilirubin correlated independently and positively, and 25-hydroxy vitamin D3 levels negatively, with bone loss at the femoral neck. CONCLUSIONS: Patients with CLD have increased bone loss at the femoral neck. Advanced liver disease is associated with increased bone loss, and hyperbilirubinaemia and low levels of vitamin D3 are predictors of increased bone loss. PMID- 11782575 TI - In the European population HLA-class II genes are not associated with Helicobacter pylori infection. AB - OBJECTIVE: Genetic variability influences susceptibility to several diseases and depends on the specific ethnic background of individuals. HLA-class II genes have repeatedly been investigated as candidate genes for predisposition to Helicobacter pylori infection. Certain HLA-DQA1 alleles have been reported to be associated with gastric and duodenal ulcer disease in infected patients in the Japanese population. But conflicting results were reported on European and Japanese populations. METHODS: HLA-DRB1 typing of 382 German individuals with well-defined H. pylori status and different clinical course of the disease was performed by polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULTS: No association with the infection status itself was observed in the German cohort. Similar results have been found in other European populations. In contrast, re-analysis of published data in a Japanese cohort revealed a highly significant association of DRB1*1501 with uninfected controls (P = 0.00035). In the German population, the carrier frequency of DRB1*15 was higher in H. pylori-positive individuals with gastric or duodenal ulcer but without statistical significance (gastric ulcer: odds ratio, 2.13; chi2 = 3.77; P = 0.05; Bonferroni correction, Pc = not significant; and duodenal ulcer: odds ratio, 2.15; chi2 = 3.4; P = 0.06; Pc = not significant). In infected individuals, autoantibodies to gastric mucosa were investigated, but no statistical significant difference in carrier frequencies of HLA-DRB1 alleles was evident. CONCLUSION: The DRB1*1501-DQA1*01021-DQB1*0602 haplotype seems to provide protection from H. pylori infection in the Japanese population, whereas genetic variability in HLA-class II genes has only a minor impact on H. pylori infection and its clinical course in the European population. PMID- 11782576 TI - One-year prognosis of primary care dyspepsia: predictive value of symptom pattern, Helicobacter pylori and GP management. AB - BACKGROUND AND AIMS: Dyspepsia is a highly prevalent, heterogeneous condition with a poorly defined clinical course in family practice. We observed its clinical outcome and identified prognostic factors. PATIENTS: We studied 583 patients presenting to their general practitioner (GP) with a new episode of dyspeptic complaints. METHODS: A validated dyspepsia severity score was used to observe deterioration of dyspepsia. Furthermore, the general health status and the patient's perception of no improvement were registered. As prognostic determinants, demographic characteristics, concomitant conditions, and management were studied. Univariate and multivariate analyses were performed. RESULTS: A total of 518 (89%) patients completed the 1-year follow-up. Of these, 111 patients (22%, 95% CI 18% to 25%) had a negative change in their dyspepsia score after 1 year; 46 patients (9%, 95% CI 6% to 11%) noted impairment of general health; and 122 patients (24%, 95% CI 20% to 28%) regarded complaints as not improved. Frequent dyspepsia (>1 episode/year) and a history of peptic ulcer predicted deterioration of dyspepsia, while smoking and little psychological distress predicted impairment of general health. Eradication of Helicobacter pylori reduced the chance of patient's negative judgement for especially those with frequent dyspepsia. CONCLUSION: One-quarter of the dyspepsia patients had an unfavourable 1-year prognosis, which was predictable because of frequent complaints and previously diagnosed ulcers. Psychological factors need to be identified, since they are related to general health improvement. The observed benefit of H. pylori eradication on perceived improvement of complaints may well be placebo effect. PMID- 11782577 TI - Efficacy of Helicobacter pylori eradication in uninvestigated chronic dyspeptic staff members of a large factory: a prospective, long-term, follow-up, workplace outcome study. AB - BACKGROUND: Current European guidelines propose Helicobacter pylori eradication for the initial management of patients under 45 years with uninvestigated dyspepsia without alarm symptoms. Until now, no study has assessed this strategy in occupational medicine. AIM: To investigate the outcome of H. pylori eradication in staff members of a large factory with uninvestigated chronic dyspepsia in a prospective, open, controlled, workplace outcome study in terms of the 1 year follow-up of dyspepsia and quality of life. METHODS: In 267 subjects with uninvestigated chronic dyspepsia (229 males, mean age 42 years; range 22-62 years) H. pylori status was assessed by using the 13C-urea breath test at baseline. H. pylori-positive subjects were offered 1 week eradication therapy with omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d., and were retested after 2 months. Subjects with a negative 13C-urea breath test at 2 months were H. pylori-responders; subjects still H. pylori positive at this time were H. pylori-nonresponders. H. pylori-negative subjects at baseline were included as a reference. Dyspeptic symptoms, quality of life and health care utilization were assessed by questionnaires at baseline (T0), and at 2 (T2) and 12 months (T12). RESULTS: One hundred and eleven of 267 (41.65%) subjects were H. pylori-positive at baseline. The infection was cured in 85 of 94 (90.4%) subjects. Upper abdominal pain and dyspeptic symptoms were significantly reduced and quality of life significantly increased in H. pylori responder subjects at T12 compared to baseline and to reference subjects (P < 0.01). At T12 42.3% of H. pylori responder subjects showed complete relief of epigastric pain compared to 9.2% in the reference group (P < 0.001). Furthermore, disease-related absence from work, visits to family physicians, and antacid consumption significantly decreased in H. pylori responder subjects compared with reference subjects (P < 0.05). CONCLUSION: These data suggest that an H. pylori test-and treat strategy in occupational medicine is effective for improving uninvestigated dyspepsia and quality of life and it may reduce dyspepsia related health care costs at a level of occupational medicine. PMID- 11782578 TI - Tissue transglutaminase and endomysial autoantibodies measured in an historical cohort of children and young adults in whom coeliac disease was suspected. AB - OBJECTIVE: To evaluate whether anti-endomysial and anti-transglutaminase antibodies are relevant important markers of coeliac disease in an historical group of patient sera. DESIGN: Sera from 196 children suspected to suffer from coeliac disease were analysed for these antibodies. METHODS: A total of 233 serum samples were obtained simultaneously with a biopsy. Coeliac disease was confirmed in 37 (19%) patients. Antibodies against guinea pig transglutaminase were determined by enzyme-linked immunosorbent assay (ELISA); endomysial antibodies were determined by immunofluorescence. RESULTS: In 17 samples, immunoglobulin A (IgA) anti-transglutaminase levels were increased; 16 of these came from coeliac patients. High levels correlated with high prediagnostic or challenge-related gluten intake. The additional anti-transglutaminase-positive patient was assumed to suffer from sequelae to gastroenteritis. CONCLUSIONS: Raised IgA anti transglutaminase levels were correlated with presence of coeliac disease. Negative tests were seen in some coeliac patients when on a gluten-containing diet. The IgA anti-transglutaminase test using guinea pig antigen was less sensitive than anti-endomysial antibodies but rather specific for active coeliac disease. In our study, anti-endomysial antibodies were more specific than anti transglutaminase antibodies for active coeliac disease. PMID- 11782579 TI - Giant benign cystic mesothelioma: a case report and review of literature. AB - A 28-year-old man was admitted because of weight loss and a huge abdominal mass. The abdominal cavity was filled by a large number of cysts with a maximum diameter of 10 cm as diagnosed by ultrasound and computed tomography. Laparotomy was performed and a 33 kg cystic tumour originating from the peritoneum was resected en bloc. Histopathological work-up showed multiple cysts covered by cubic or flat mesothelial cells with uniform nuclei. The final diagnosis was benign cystic mesothelioma. Twenty-three months after surgical debulking, a follow-up computed tomography scan showed recurrence of the disease. In this report, we describe the characteristics, aetiology and differential diagnosis of this rare lesion. PMID- 11782580 TI - Spontaneous bacterial peritonitis caused by quinolone-resistant Escherichia coli: could steroid therapy play a role? AB - Prophylaxis with norfloxacin has been shown to be effective in preventing spontaneous bacterial peritonitis (SBP) in liver cirrhosis. This therapy is associated with the appearance of quinolone-resistant Escherichia coli. However, only four cases of SBP caused by quinolone-resistant E. coli have been reported so far. We present four cases of quinolone-resistant E. coli SBP in three patients receiving oral quinolones, and who were on corticosteroid therapy to treat associated disorders. PMID- 11782581 TI - Giant benign true cyst of the spleen with high serum level of CA 19-9. AB - We report the case of a 21-year-old woman with a giant (20 cm) benign mesothelial splenic cyst and a high CA 19-9 serum level (1240 U/ml). The patient underwent resection of the cyst and splenectomy. True non-parasitic splenic cysts are very rare. Only 10 cases of benign true splenic cysts, with a high CA 19-9 serum level, have ever been published in the medical literature written in English. These are reviewed in this paper. We believe that the inner cellular lining of the cyst wall produces CA 19-9, which causes the high CA 19-9 serum level. This is supported by the facts that (1) the inner cellular lining is strongly positive for immunohistochemistry with CA 19-9, and (2) the CA 19-9 serum level returned to normal after resection of the cyst. PMID- 11782582 TI - The accuracy of the Helicobacter pylori stool antigen test in diagnosing H. pylori in treated patients. PMID- 11782584 TI - Nonpathogenic lion and puma lentiviruses impart resistance to superinfection by virulent feline immunodeficiency virus. AB - Lion lentivirus (LLV) and puma lentivirus (PLV) exist as highly divergent virus clades among populations of indigenously infected nondomestic Felidae. The feline immunodeficiency virus (FIV) is highly divergent from LLV and PLV and is pathogenic for domestic cats. When domestic cats are infected with LLV or PLV, they have immunologically and clinically silent persistent infections. We examined whether LLV or PLV infection might impart resistance to FIV superinfection in vitro by infecting domestic cat lymphoid cells with PLV and assessing resistance of these cells to FIV. We found that infection with FIV was highly restricted by prior established PLV infection. To examine whether this resistance applied in vivo, domestic cats were asymptomatically infected with either LLV or PLV and then challenged with pathogenic FIV. Although all cats became infected with FIV, prior LLV or PLV exposure blunted CD4 + cell depletion and suppressed plasma and peripheral blood mononuclear cell FIV loads relative to FIV-challenged controls not infected with LLV or PLV, despite the lack of prechallenge neutralizing antibody activity against FIV. Thus, as compared with naive controls, cats previously infected with LLV or PLV were able to more effectively control FIV infection and resist its immunologic effects, despite the substantial genetic divergence between these lentiviruses-raising the possibility that superinfection may impart resistance to lentivirus infection by heightening innate immune mechanisms. PMID- 11782585 TI - Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails. AB - Amdoxovir ([-]-beta-D-2,6-diaminopurine dioxolane [DAPD]) is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against HIV-1. DAPD is deaminated in vivo by adenosine deaminase to (-)-beta-D-dioxolane guanosine (DXG), a highly active anti-HIV compound. The median 50% effective concentrations (EC 50 ) +/- SD (representing antiviral activity against a laboratory-derived HIV-1 isolate) for DAPD and DXG in peripheral blood mononuclear cells were 4.0 +/- 2.2 micromol/L and 0.25 +/- 0.17 micromol/L, respectively. The 50% cytotoxic dose (CC 50 ) of both DAPD and DXG was >500 micromol/L. Recombinant viruses and clinical isolates of HIV-1 from patients for whom NRTI therapy and/or nonnucleoside reverse transcriptase inhibitor (NNRTI) combination therapies failed remained susceptible to inhibition by DXG (less than fourfold change in EC 50). Similar analysis showed that recombinant viruses harboring mutations known to confer resistance to NRTIs (zidovudine, lamivudine, and abacavir) and NNRTIs (efavirenz and nevirapine) as well as the multidrug resistance-associated mutation Q151M and double codon insertions (SS and SG) were also susceptible to inhibition by DXG. Resistance to DXG was observed only in recombinant isolates containing the 65R and 151M double mutations. Phenotypic analysis of a site-directed mutant containing only the 151M mutation demonstrated moderate resistance to DXG (<10 fold change in EC 50). We also examined site-directed mutants containing only L74V or K65R, the characteristic resistance mutations for DXG. The L74V mutant remained susceptible to inhibition by DXG, and the K65R mutant demonstrated moderate resistance to DXG. PMID- 11782587 TI - Leptin and adipose tissue maldistribution in HIV-infected male patients with predominant fat loss treated with antiretroviral therapy. AB - BACKGROUND: Metabolic disturbances and fat maldistribution are main features of the antiretroviral-related lipodystrophy syndrome (LDS). Different phenotypes of fat distribution abnormalities can be observed: fat loss, fat accumulation, or a mixed pattern. In patients with predominant loss of fat, the roles of leptin, lipids, and glucose homeostasis disturbances have not yet been clearly established. METHODS: The study comprised 34 HIV-infected male patients receiving antiretroviral treatment that included protease inhibitors. A lipoatrophic phenotype, defined as fat loss in face or extremities, both normal weight and waist:hip ratio, and absence of fat accumulation elsewhere, was present in all cases. Fat distribution disturbances were confirmed by abdominal and midthigh computed tomography-calculated adipose tissue content. Fasting plasma glucose, insulin, proinsulin, total leptin, testosterone, and lipid profiles were measured. After 2 hours, 75-g oral glucose tolerance test (OGTT), glucose, insulin, and proinsulin levels were also obtained. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA-r) method. Both healthy study subjects ( n = 385) and antiretroviral-naive HIV positive patients ( n = 13) were used as controls. RESULTS: Of these LDS patients, 5.8% showed diagnostic criteria for diabetes and 17.8% for impaired glucose tolerance. A lipid pattern characterized by high total cholesterol and high low density lipoprotein (LDL) plasma levels, hypertriglyceridemia, and normal high density lipoprotein (HDL) levels was observed. Fasting insulin and 2 hour post OGTT insulin levels, and insulin resistance index were significantly higher in LDS patients than in antiretroviral-naive HIV-positive patients. Plasma leptin levels were significantly lower in lipoatrophic patients than in healthy control individuals. Patients with LDS presented with significant midthigh fat reduction and visceral fat accumulation compared with findings in antiretroviral naive HIV-positive patients. A significant correlation was found between plasma leptin levels and midthigh fat content. CONCLUSION: Peripheral fat loss in extremities in LDS patients with lipoatrophic phenotype is also associated with low plasma leptin levels, visceral fat accumulation, and metabolic disturbances related to an increased cardiovascular risk. In LDS patients, plasma leptin levels could be a marker of subcutaneous adipose tissue content. PMID- 11782586 TI - Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1 infected patients treated with two nucleoside reverse transcriptase inhibitors. AB - BACKGROUND: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). OBJECTIVES: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. DESIGN: Prospective cohort study. PATIENTS AND METHODS: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. RESULTS: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p =.004). The risk of developing any BHC was significantly higher in female patients (p <.0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p =.04) and in those who had previously received ART (p =.02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p =.02), whereas age was associated with the development of hyperglycemia (p =.0096). CONCLUSIONS: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved. PMID- 11782588 TI - Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. AB - To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection. PMID- 11782589 TI - Cellular immune response in HIV-infected patients with histoplasmosis. AB - The relationship of immunity to Histoplasma capsulatum and CD4 count in HIV-1 infected patients is unknown. Samples of blood from people with HIV infection and from HIV-negative volunteers were assessed for immune responsiveness to the histoplasmin antigen using proliferation and interferon-gamma production as indicators of immunity. Results of histoplasmin skin tests, lymphoproliferative responses (LPR), and interferon-gamma production were positive in 9 of 20 (45%) HIV-negative controls, and in vitro measurements agreed highly with skin test reactivity. Among HIV-1-infected patients with recent histoplasmosis, skin test results were positive in none, LPR results were positive in 14%, and interferon gamma production in 18%. Among HIV-1-infected patients with CD4 counts between 200 and 500 cells/mm(3), LPR was positive in 8% and interferon-gamma production in 33%, and among those with CD4 counts >500 cells/mm(3), LPR was positive in 31% and interferon-gamma production in 46%. In conclusion, immune responsiveness to H. capsulatum was depressed in HIV-1-infected persons with CD4 counts between 200 and 500 cells/mm(3), but approached normal in those with CD4 counts >500 cells/mm(3). PMID- 11782590 TI - Anemia in HIV-infected patients receiving highly active antiretroviral therapy. AB - BACKGROUND: Anemia is common in HIV infection, particularly in advanced disease states. We wished to determine how highly active antiretroviral therapy (HAART) and other factors affected the level of hemoglobin in HIV infection. METHODS: We analyzed data from 905 patients receiving care at Johns Hopkins in Baltimore, Maryland after July 1, 1996. Analyses were done of hemoglobin levels obtained at baseline and during 1 year of follow-up in patients who received and did not receive a HAART regimen. Use of HAART and other demographic and clinical factors were examined. RESULTS: Eleven percent of patients had a hemoglobin count <10 g/dL, 27% had a hemoglobin count 10 to 12 g/dL, and 21% had a hemoglobin count of >14 g/dL at baseline before HAART was started. During 1 year of follow-up, use of HAART was associated with a hemoglobin levels >14 g/dL in 42% of patients, irrespective of use of zidovudine as part of HAART regimen, compared with 31% of patients who did not use HAART. In multivariate analysis, use of HAART was strongly associated with not having anemia during 1 year of follow-up, adjusting for patient gender, race, injection drug use history, baseline CD4 and HIV-1 RNA levels, and anemia treatments. CONCLUSIONS: HAART is an effective treatment of the anemia of HIV infection. Patients who continue to have symptomatic anemia while receiving HAART may need additional intervention. PMID- 11782591 TI - Brief report: two-year outcome of a multidrug regimen in patients who did not respond to a protease inhibitor regimen. AB - In most studies, people who have not responded virologically to a protease inhibitor (PI)-containing regimen have tended to experience poor virologic responses to subsequent regimens. We describe the 2-year viral load, CD4 count, and clinical outcome of a multidrug regimen used in 60 people who had not responded virologically to a PI-containing regimen. At baseline, median CD4 count was 126/mm(3) (nadir 30/mm(3) ) and median viral load was 320,000 copies/mL. A median of five antiretroviral drugs had previously been used, of which a median of two were PIs. Of these patients, 16% had previously used another nonnucleoside reverse transcriptase inhibitor besides efavirenz. The multidrug regimen (median 5 drugs) started most commonly included efavirenz (100%), at least one PI (92%, usually indinavir/ritonavir), didanosine (78%), and hydroxyurea (74%). At year 2, 5 patients had died and 5 had no measure available. Nine patients developed a new AIDS event and 10 patients were known to have stopped all antiretroviral therapy. Thirty-one patients (52% of the whole group, 72% of those remaining on therapy with viral load value available) had viral load <50 copies/mL. Thus, a substantial proportion of patients who had failed to respond virologically to PI containing regimens can achieve profound and sustained virologic suppression with a multidrug regimen. PMID- 11782592 TI - HIV infection in young men in northern Thailand, 1991-1998: increasing role of injection drug use. AB - Epidemic HIV-1 infections were first recognized in Thailand in 1988 but increased dramatically in the 1990s primarily as a result of sexual transmission. The Ministry of Public Health instituted programs, including condom promotion during commercial sex, and health education to prevent HIV transmission. We assessed the HIV infection prevalence and risk behaviors among eight cohorts of 21-year-old randomly selected male military conscripts in northern Thailand between 1991 and 1998 to evaluate temporal trends in HIV infection and risk behavior. The prevalence of HIV was 11.4% to 11.9% in 1991 through 1993 and progressively fell to 2.4% in 1998. The men reported progressive decreases in commercial sex from 80% in 1991 to 38% in 1998, increases in condom use for commercial sex to greater than 95% in 1998, and decreases in lifetime history of a sexually transmitted infection from 42% in 1991 to 4.4% in 1997. There was an increasing proportion of men who reported a history of injecting illicit drugs, however, which involved 1.0% of the men in 1991 but 4.2% in 1997. The population attributable risk of drug use for HIV infection increased in recent years; the proportion of HIV positive men with a history of drug use increased from 1.0% in 1991 to 25.8% in 1998. The public health program to prevent the sexual transmission of HIV in Thailand continues to be highly successful. Nevertheless, injection drug use has emerged as an important risk behavior and is maintaining endemic HIV transmission in Thailand. PMID- 11782593 TI - Use of highly active antiretroviral therapy in HIV-infected women: impact of HIV specialist care. AB - OBJECTIVES: To evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care. DESIGN: Cross sectional analysis of the 1998 interview from the HIV Epidemiology Research Study (HERS) cohort. METHODS: Data from 273 HIV-infected women in the HERS were analyzed by multiple logistic regression to calculate predictors of the use of HIV specialist care providers. Variables included study site, age, education, insurance status, income, substance abuse, depression, AIDS diagnosis, CD4 + lymphocyte count, and HIV-1 viral load. In addition, medical indications for therapy and medical advice to begin antiretroviral therapy were assessed. RESULTS: Of 273 women, 222 (81%) used HIV specialists and 51 (19%) did not. Having health insurance, not being an injection drug user, and being depressed were predictive of using HIV specialist care (all p < or = .05). Although medical indications for therapy in the two groups were comparable, the rate of highly active antiretroviral therapy (HAART) use was significantly higher in women using HIV specialist care (27%) compared with those not using HIV specialists (7.8%). Women using HIV specialists received significantly more advice to begin antiretroviral therapy (ART) in the 6 months prior to the interview compared with those not using specialists (relative risk, 2.4; 95% CI = 1.3-4.6). CONCLUSIONS: Having insurance, not being an injection drug user, and being depressed all increased the likelihood of women receiving HIV specialty care, which, in turn, increased the likelihood of receiving recommended therapies. The level of HAART use (23%) and any ART use (47%) in these HIV-infected women was disturbingly low. Despite comparable medical indications, fewer women obtaining care from other than HIV specialists received HAART. These data indicate substantial gaps in access to HIV specialist care and thereby to currently recommended antiretroviral treatment. PMID- 11782594 TI - Repeat HIV testing, risk behaviors, and HIV seroconversion among young men who have sex with men: a call to monitor and improve the practice of prevention. AB - OBJECTIVES: We compared recent risk behaviors and HIV seroconversion among young men who have sex with men (MSM) who were first-time, infrequent, and repeat HIV testers. METHODS: Male adolescents and young men aged 15 to 22 years were randomly sampled, interviewed, counseled, and tested for HIV at 194 gay identified venues in seven U.S. cities from 1994 through 1998. Analyses were restricted to MSM who reported having never tested or last tested HIV-negative. RESULTS: Of 3430 participants, 36% tested for the first time, 39% had tested infrequently (one or two times), and 26% had tested repeatedly (> or = three times). Compared with first-time testers, repeat testers were more likely to report recent risk behaviors and to acquire HIV (7% versus 4%). Over 75% of repeat testers who seroconverted acquired HIV within 1 year of their last test. Compared with repeat testers, first-time testers reported similar use of health care but delayed testing for nearly 2 additional years after initiating risk. CONCLUSIONS: Many young MSM soon acquire HIV after repeated use of HIV counseling and testing services. Providers must strengthen practices to identify, counsel, and test young MSM and provide enhanced behavioral interventions for those with persistent risks. PMID- 11782595 TI - Incarceration and risk for HIV infection among injection drug users in Bangkok. AB - OBJECTIVE: To assess potential multiple relationships between incarceration and HIV infection among injecting drug users (IDUs) in Bangkok. Previous cross sectional studies have shown strong relationships between incarceration and HIV infection but have not been able to assess potential causal pathways. METHODS: Injection drug users seen at methadone treatment programs in Bangkok were screened during 1995 to 1996 for enrollment into the study. With informed consent, 1,209 seronegative IDUs were enrolled in a cohort study to determine HIV incidence and identify factors associated with incident infections. Follow-up visits were conducted every 4 months, with HIV testing and assessment of risk behaviors. RESULTS: Overall incidence rate was 5.8 per 100 person-years (95% confidence interval [CI], 4.8-6.8) of follow-up. A four-step "injection risk" scale was constructed that included less frequent than daily injection, daily injection, daily injection with reported sharing of injection equipment, and injection while incarcerated. This scale was strongly related to HIV incidence, with incidence approximately doubling for each step in the scale. Incidence rate for follow-up periods that contained drug injection while incarcerated was 35/100 person-years at risk. In multivariate analyses, incarceration was related to incident HIV infection in multiple ways: previous incarceration and recent incarceration without drug injection, and the injection risk scale were all independently predictors of incident HIV infection. CONCLUSIONS: Incarceration is related to incident HIV infection through multiple pathways. Previous incarcerations are likely to serve as markers for unmeasured high-risk behaviors, and it is also highly likely that HIV is transmitted during periods of incarceration. Programs to reduce HIV transmission in jails and prisons, including drug abuse treatment of inmates and programs to reduce the likelihood of incarceration of IDUs, are needed urgently. Given the current diffusion of injecting drug use, of HIV infection among drug injectors, and of the common policy of incarcerating drug users, it is very likely that the problem of HIV transmission in jails and prisons is increasing in many countries throughout the world. PMID- 11782596 TI - The association of socioeconomic status and use of crack/cocaine with unprotected anal sex in a cohort of men who have sex with men in Rio de Janeiro, Brazil. AB - To evaluate the relation between illicit drug use, sexual practices, and socioeconomic status, we analyzed data from the baseline interview of a cohort of 675 men who have sex with men conducted from 1994 to 1999 in Rio de Janeiro, Brazil. Bivariate analyses of factors associated with crack/cocaine use with sex revealed that men who reported crack/cocaine use were significantly ( p <.05) more likely than men who did not report drug use to be unemployed (42.7% vs. 29.1%), to have an income of <$250 per month (70.7% vs. 60.9%), to have <8 years of education (69.5% vs. 50.9%), to report bisexual activity (81.7% vs. 41.7%), and to engage in commercial sex (72.0% vs. 37.9%). Multivariate analysis of factors associated with unprotected anal sex with casual male partners in the last 6 months demonstrated that the following variables were associated with this outcome: an income <$250 per month (adjusted odds ratio [AOR] = 1.73, 95% confidence interval [CI]: 1.04-2.87), less than 8 years of education (AOR = 2.21, CI: 1.38-3.53), a greater sense of vulnerability (AOR = 2.58, CI: 1.54-4.33), a willingness to participate in vaccine trials (AOR = 1.91, CI: 1.20-3.05), and use of crack/cocaine (AOR = 1.91, CI: 1.05-3.46). Our findings suggest that HIV prevention programs for these men need to address drug use and how drug use may influence sexual behaviors. PMID- 11782597 TI - Pharmacokinetic variability caused by gender: do women have higher indinavir exposure than men? PMID- 11782598 TI - Multidrug-resistant HIV-1 RNA and proviral DNA variants harboring new dipeptide insertions in the reverse transcriptase pol gene. PMID- 11782599 TI - How many people are at risk for HIV in the United States? The need for behavioral surveys of at-risk populations. PMID- 11782600 TI - Excess mortality from liver disease and other non-AIDS-related diseases among HIV infected individuals in Italy. PMID- 11782601 TI - Laparoscopic surgery and the nuances of systemic immunity. PMID- 11782602 TI - Dysplasia of the gut: the diagnosis is harder than it seems. AB - Preneoplastic epithelia of the gut have been given several different names, but the one most often used is dysplasia. Dysplasias of the gut are diagnosed by pathologists, using a set of cytologic and architectural features, and are divided into two grades: low- and high-grade. Although the definitions imply that all low-grade dysplasias are similar (as are all high-grades), in reality, there is significant heterogeneity in the appearances of each grade of dysplasia. Thus, separating low-from high-grade epithelium may be difficult. In addition, the features that characterize low-grade epithelia are very similar to many examples of epithelial regeneration, and so these may not be readily separable. Such cases may be classified as being indefinite for dysplasia. For these reasons, and because the implications for patient care are significant, the interpretations of biopsies taken for dysplasia surveillance are considered challenging by most pathologists. Clinicians must understand the challenging nature of these biopsies, communicate with the pathologists who will interpret such biopsies, and obtain an adequate sample of the mucosa to ensure that dysplasia, if present, will be biopsied and appropriately diagnosed. PMID- 11782603 TI - The role of eicosanoids, cyclooxygenases, and nonsteroidal anti-inflammatory drugs in colorectal tumorigenesis and chemoprevention. AB - There is mounting evidence from studies on experimental cancer in rodents, interventional studies in patients with familial adenomatous polyposis, and some, but not all, epidemiologic investigations, that suggests a chemopreventive effect of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer. In addition, the mechanisms by which these agents modulate tumorigenesis are being elucidated in laboratory experiments. Currently available NSAIDs are unlikely to have an acceptable benefit-to-risk ratio for long-term use in an asymptomatic population. Once the discrete chemopreventive mechanisms are established and the genetic background and risk factor profile of individuals who will benefit from chemoprevention are clarified, a low-dose combination of NSAIDs with different targets may optimize efficacy and minimize toxicity. At present, however, colectomy is still the treatment of choice for patients with familial adenomatous polyposis, and early screening and regular surveillance colonoscopies are the choices for those at risk for hereditary nonpolyposis colorectal cancer. In the average-risk individual, endoscopic screening and surveillance will remain the core of efforts to prevent sporadic colorectal cancer. PMID- 11782604 TI - Gastrointestinal uses of botulinum toxin. AB - Botulinum toxin was initially used in medicine to produce a potent neuromuscular blockade. It was later found to interfere with acetylcholine release in the myenteric plexus and inhibit contraction in gastrointestinal smooth muscle, leading to its use in the treatment of various conditions. It is frequently used in the treatment of achalasia in elderly patients who may be poor surgical candidates. It has been used successfully in the management of various conditions, including anal fissure and biliary dyskinesia. Large controlled trials are needed to establish the role of botulinum toxin and its safety in gastroenterology. PMID- 11782605 TI - Recurrence of Helicobacter pylori infection and the long-term outcome of peptic ulcer after successful eradication in Japan. AB - Recurrence of peptic ulcer after successful eradication of Helicobacter pylori is closely associated with reinfection. The aim of this study was to examine the recurrence of peptic ulcer and reinfection with H. pylori after successful eradication. To eradicate H. pylori infection, patients with active peptic ulcer disease were assigned to two treatment groups depending on the year of their enrollment (AM group and OAMR group). Patients in the AM group received 400 mg of cimetidine twice per day, 300 mg of amoxicillin three times per day, and 250 mg of metronidazole three times per day for 2 weeks. Patients in the OAMR group received 20 mg of omeprazole once per day, 500 mg of amoxicillin granules three times per day, 250 mg of metronidazole three times per day, and 150 mg of roxithromycin twice per day for 1 week. After endoscopy verified ulcer scarring and successful eradication of H. pylori infection, study patients were followed up monthly and did not undergo acid-suppressive therapy. Endoscopy was performed at 6-month intervals for the 1st year. After the 1st year, follow-up endoscopies were performed annually. In total, 107 patients with peptic ulcer (duodenal ulcer [DU], 65; gastric ulcer [GU], 42) were followed up for a mean period of approximately 2 years. Recurrence of infection occurred in 10 (9.3%) of 107 patients (AM group, 9; OAMR group, 1) after 210 patient-years of follow-up; the recurrence rate was 4.8% per patient-year. Recurrence of H. pylori infection was significantly higher in the AM group (23.1%) than in the OAMR group (1.5%). H. pylori infection recurred in two patients 6 months after eradication therapy, in seven 1 year after, and in one 2 years after. Thereafter, no further cases of H. pylori recurrence were observed. During follow-up periods, seven cases of ulcer recurrence were observed (DU, 4; GU, 3). The rate of peptic ulcer recurrence within 2 years after eradication therapy was significantly higher than that after more than 2 years. Four cases of ulcer recurrence (DU, 3; GU, 1) also had recurrence of H. pylori infection. One recurrent case of DU without reinfection was associated with nonsteroidal anti-inflammatory drugs. The remaining two cases of GU recurred without H. pylori reinfection. In conclusion, peptic ulcer recurrence rarely occurred (3 [2.9%] of 103) in patients cured of H. pylori infection. Reinfection after apparent successful eradication was rarely noted when a powerful therapeutic regimen in eradication was used. Therefore, to eradicate H. pylori, a highly effective therapeutic regimen should always be used. PMID- 11782606 TI - A comparative study between conventional and laparoscopic cholecystectomy: evaluation of phagocytic and T-cell-mediated antibacterial activities. AB - Over the past few years, many reports have pointed out that open, but not minimally invasive, cholecystectomy was associated with reduced immune functions. Also, after laparoscopic surgery, a reduced impairment of T cell functions and lower levels of proinflammatory cytokines, epinephrine, and norepinephrine were found in comparison with those detected in patients who underwent conventional cholecystectomy. We investigated polymorphonuclear cell- and monocyte-mediated phagocytosis and killing and T-cell-mediated antibacterial activity in 12 patients who underwent open cholecystectomy versus another group of 12 patients who underwent laparoscopic cholecystectomy. Our data show that polymorphonuclear and monocyte killing activities are preserved or are less affected in patients who undergo laparoscopy when compared with patients who undergo conventional operation. On the other hand, in both groups of patients, T-cell-mediated antibacterial activity was significantly reduced in the preoperative period, and, therefore, we could not draw conclusions on the effects of the surgical techniques used on the above immune parameter. The overall data suggest that laparoscopic cholecystectomy is a valid alternative to open surgery because of the moderate postoperative immune suppression and decreased risk of postsurgical infections. PMID- 11782607 TI - Detection of pyloric metaplasia may improve the biopsy diagnosis of Crohn's ileitis. AB - BACKGROUND: Pyloric metaplasia (PYME) is seen frequently in ileal resections from patients with Crohn's disease (CD). It represents a nonspecific reparative reaction in intestinal ulcers. The presence of PYME in terminal ileum biopsies (TIbxs) of CD has not received much attention and has been considered a rare finding. STUDY: We reviewed 45 TIbxs from 45 adult patients with indisputable clinicopathologic diagnosis of CD. Endoscopic biopsies were obtained with an Olympus CIF 140 videoscope. The samples were fixed in 10% buffered formalin and were processed routinely. RESULTS: Pyloric metaplasia was identified in 10 TIbxs from 10 patients. Most of the metaplastic glands formed small aggregates in the mucosal base, and they were frequently noted below regenerating crypts and in the vicinity of granulation tissue and ulceration. CONCLUSIONS: In our material, 22.2% of the TIbxs revealed PYME. The single previous study with similar data showed an incidence of 2.27%. The difference could reflect the stage of the disease or the thoroughness of the endoscopic and pathologic examinations. Pyloric metaplasia, despite its lack of specificity, remains a sensitive indicator of persistent ulceration with inflammation. Because PYME is not as rare as previously thought, it should be carefully looked for in TIbxs to support the diagnosis of CD in the appropriate clinical setting. PMID- 11782608 TI - Laparoscopy-assisted replacement of percutaneous endoscopic gastrostomy. AB - Laparoscopy-assisted percutaneous endoscopic gastrostomy was successfully performed to replace gastrostomy tubes that had been inadvertently withdrawn. With this less-invasive surgical technique, gastrostomy tubes in elderly patients can be replaced safely and definitely without laparotomy. We suggest that this technique be performed when indicated. PMID- 11782609 TI - Monoclonal gammopathy of undetermined significance predisposing to Helicobacter pylori-related gastric mucosa-associated lymphoid tissue lymphoma. AB - Gastric mucosa-associated lymphoid tissue (MALT)-associated B-cell proliferation may range from benign to malignant, and Helicobacter pylori is the only identified critical antigenic stimulus to the development of gastric MALT. Monoclonal gammopathy of undetermined significance (MGUS) is characterized by B cell hyper-activation and clonal expansion and is know to predispose to B-cell malignancies. We report a patient with MGUS and H. pylori infection in whom we noted the progression of gastritis to acquired gastric MALT and gastric MALT to MALT lymphoma during a 3-year follow-up. PMID- 11782610 TI - Endoscopic ultrasonography in multiple lymphomatous polyposis. AB - Two cases of multiple lymphomatous polyposis (MLP) are presented, involving different segments of the gastrointestinal tract. Both cases display the characteristic clinical and pathologic features of MLP. In addition, we were able to document, for the first time, the endoscopic ultrasonographic findings in this disease. This new ancillary diagnostic technique was found to be very helpful in the evaluation of the structural changes of the wall of the gastrointestinal tract and in the detection of affected lymph nodes. PMID- 11782611 TI - Low-grade follicular lymphoma of the small intestine. AB - BACKGROUND: Although the gastrointestinal tract is the most common site of extranodal non-Hodgkin's lymphoma (NHL), primary small intestine lymphomas remain relatively rare, especially localized low-grade follicular B-cell lymphomas. When lymphomas do occur at this site, most are high grade and require aggressive therapy. We report three cases of small intestinal follicular lymphoma diagnosed on endoscopic biopsy and review the clinical history, pathologic features, and treatment outcome. STUDY: A review of the medical records and pathology from three cases of small intestine follicular NHL was performed. The pathology specimens were formalin-fixed, paraffin-embedded tissues processed for routine microscopic examination, immunohistochemical staining, and molecular analysis. RESULTS: Histologic and immunophenotypical studies were diagnostic of grade 1 follicular lymphoma (Revised European-American Lymphoma classification/World Health Organization classification). All cases expressed bcl-2 protein, and polymerase chain reaction analysis supported the diagnosis in two cases with adequate DNA. With 23.3 months' median follow-up, one untreated and one treated patient were alive without symptoms; a third untreated patient died of a nonlymphoma cause. CONCLUSION: Isolated indolent lymphomas of the small intestine are rare. Accurate pathologic staging and histologic classification are paramount in delineating treatment options. PMID- 11782612 TI - Giant nonpancreatic pseudocyst causing acute anuria. AB - Giant intraabdominal cysts masquerading as ascites are not uncommon. We present a unique case of a giant intraabdominal pseudocyst that resulted in acute abdominal compartment syndrome, leading to anuria and acute renal failure. A 52-year-old woman with known severe cardiac dysfunction presented with generalized edema, marked abdominal distension, and decreased urine output. She was initially presumed to have congestive heart failure with refractory ascites. She became completely anuric. A diagnosis of intraabdominal compartment syndrome from a giant cyst was ultimately made after careful review of her abdominal imaging. Urgent drainage and subsequent marsupialization of the giant pseudocyst resulted in immediate diuresis and a subsequent return to her baseline renal function. As this case illustrates, differentiation of pseudoascites from true ascites may be difficult in a clinical setting or using laboratory studies. A clear differentiation can usually be made using imaging studies, mainly magnetic resonance imaging, computerized axial tomography, or ultrasound. To our knowledge, this is the first case report of a nonrenal pseudocyst or cyst leading to acute renal failure from extrinsic compression. Abdominal compartment syndrome needs to be considered in the differential diagnosis of patients with acute renal failure and presumed large-volume ascites. PMID- 11782613 TI - Collagenous colitis associated with lansoprazole. AB - BACKGROUND: Collagenous colitis is a diarrheal illness of unknown cause. The purpose of this report is to describe a case of collagenous colitis related to lansoprazole exposure. STUDY: Case report. RESULTS: A patient is described who developed clinical and pathologic findings of collagenous colitis during treatment with lansoprazole and omeprazole. Symptoms of diarrhea and histopathologic abnormalities resolved after drug withdrawal and recurred with re exposure to lansoprazole. CONCLUSIONS: The observations are compatible with collagenous colitis or lymphocytic colitis associated with exposure to lansoprazole. PMID- 11782614 TI - Prognostic factors in acute pancreatitis. AB - The assessment of the severity of acute pancreatitis (AP) is a critical early step in its management, as severity of AP predicts prognosis. A range of options are available for assessment of severity in AP, including clinical evaluation, standardized prognostic criteria, computed tomography (CT), and biochemical markers. Clinical assessment has limited accuracy for predicting severity early in the course of AP. Therefore, additional assessment using biochemical and radiologic criteria in combination with standardized criteria is appropriate to determine severity and prognosis in AP; a strategy emphasizing daily assessment of severity should be used. The APACHE II is the scoring system of choice for evaluating severity in AP, although it remains an imperfect tool. Computed tomographic grading of AP and the development of the CT severity index allow for heightened accuracy in the prediction of severity. C-Reactive protein is the standard for serum marker assessment of severity and prognosis in AP; other markers, including interleukin-6, polymorphonuclear elastase, and trypsinogen activation peptide, hold promise. The focus of this review is to examine the role of diagnostic tests in evaluating severity and predicting prognosis among patients with AP and to provide a diagnostic algorithm for initial management. PMID- 11782615 TI - High-dose interferon alfa-2b and ribavirin in patients previously treated with interferon: results of a prospective, randomized, controlled trial. AB - BACKGROUND: Kinetic studies have demonstrated a more rapid reduction in hepatitis C virus (HCV) RNA levels among patients taking high daily doses of interferon compared with those taking standard-dose interferon. GOALS: To compare the efficacy and safety of high-dose interferon alfa-2b and ribavirin with standard dose interferon alfa-2b and ribavirin in chronic hepatitis C patients previously treated with interferon. STUDY: One hundred seven patients (30 interferon relapsers and 77 interferon nonresponders) were randomized to take either high dose interferon alfa-2b in combination with ribavirin (group A) (consisting of 5 MU/d for 4 weeks, 5 MU three times weekly for 8 weeks, and then 3 MU three times weekly for 36 weeks) or standard-dose interferon alfa-2b and ribavirin (group B) for 48 weeks. Serum alanine transaminase (ALT), HCV RNA levels, and safety data were prospectively collected and compared during treatment and at week 24 of follow-up. RESULTS: The mean serum ALT and HCV RNA levels, as well as the proportion of patients with genotype 1 and cirrhosis and who were African American, were similar in the two treatment groups at study entry. The rates of suppression of HCV RNA to undetectable levels at weeks 4, 12, and 48 were similar. In addition, the sustained virologic response rates at week 24 of follow up were similar in groups A and B (29% vs. 39%, respectively, p = 0.277). Clinical variables that correlated with a sustained virologic response included a history of relapse to previous interferon therapy and non-1 HCV genotype ( p < 0.01). CONCLUSIONS: Short-term, high-dose interferon alfa-2b and ribavirin failed to demonstrate a tangible benefit compared with standard-dose interferon alfa-2b and ribavirin. However, our study results and others suggest that standard-dose interferon and ribavirin for 48 weeks should be considered for selected patients who did not respond to previous interferon therapy. PMID- 11782616 TI - The clinical and cholangiographic picture of hepatic clonorchiasis. AB - BACKGROUND: Hepatic clonorchiasis is endemic in areas of the Far East, including Taiwan, where people commonly eat raw or partially cooked freshwater fish. GOALS: To analyze and explore the cholangiographic findings of hepatic clonorchiasis with respect to the clinical data. STUDY: From February 1990 to May 1999, 64 patients were diagnosed with hepatic clonorchiasis in the Kaoshiung Veterans General Hospital. Eighteen of the 64 patients were indicated for endoscopic retrograde cholangiopancreatography (ERCP). The final diagnosis was confirmed by identification of ova in bile or worms in the biliary tract. RESULTS: Fifteen (83%) of 18 patients had history of raw fish consumption and seven patients (39%) came from an endemic area. Clinically, cholangitis (8 of 18) was the most frequent indication for ERCP. All of the patients were diagnosed by the presence of ova in bile. Only seven (39%) patients had peripheral eosinophilia, and seven (39%) had ova in stool. The most characteristic cholangiographic finding of hepatic clonorchiasis in ERCP is filamentous or elliptic filling defects of the biliary tract (16 of 18). CONCLUSION: When presented with biliary symptoms, a history of raw fish consumption in an endemic area should arouse suspicion of hepatic clonorchiasis. Filamentous filling defects in ERCP with bile analysis may confirm the diagnosis. PMID- 11782617 TI - Paraesophageal hernia repair and deep vein thrombosis. PMID- 11782618 TI - Radiotherapy-induced gastroparesis: an unusual complication. PMID- 11782619 TI - Helicobacter pylori seroprevalence in patients with pulmonary tuberculosis. PMID- 11782620 TI - Lamivudine therapy for chronic hepatitis B in a Mediterranean population. PMID- 11782621 TI - Hemobilia and jaundice caused by acalculous cholecystitis. PMID- 11782622 TI - Pierre Robin syndrome and portal hypertension: a rare association. PMID- 11782623 TI - Jejunocolic fistula: an unreported complication of acquired immunodeficiency syndrome-associated lymphoma. PMID- 11782625 TI - The role of plain films and computed tomography in the evaluation of scapular neck fractures. AB - OBJECTIVE: To assess the ability of plain films and computed tomography scans to show the pattern, displacement, and angulation of scapular neck fractures. To assess the ability of computed tomography to identify concomitant occult shoulder injuries. DESIGN: Masked retrospective radiographic review. SETTING: Level I trauma center. PARTICIPANTS: Three orthopaedic surgeons (two attending physicians and one senior resident) and one musculoskeletal radiology attending physician reviewed the imaging studies of scapula neck fractures in twenty patients treated at our institution. MAIN OUTCOME MEASURES: Kappa analysis of agreement of fracture characteristics and benefits of computed tomography for scapular neck fractures. RESULTS: The mean weighted kappa coefficient for interobserver reliability of fracture displacement was 0.49 when the fractures were assessed by plain films alone, 0.15 when they were assessed by computed tomography scans alone, and 0.35 when they were assessed by plain films and computed tomography scans. The mean weighted kappa coefficients for fracture angulation were 0.30, 0.23, and 0.16, respectively. The mean simple kappa coefficients for fracture classification were 0.81, 0.20, and 0.33, respectively. Concomitant injury to the superior shoulder suspensory complex was seen in 57 percent of cases, including nine clavicle fractures, one coracoid fracture, and three acromion process fractures. The coracoid fracture and two of the acromion process fractures were minimally displaced and seen on computed tomography scans only. CONCLUSION: Scapular neck fracture displacement, angulation, and anatomic classification showed moderate interobserver reliability by plain films but were not enhanced by computed tomography. Computed tomography confused, rather than clarified, the assessment of these characteristics. Computed tomography may be useful to identify associated injuries to the superior shoulder suspensory complex, which can be missed by plain films alone. Routine computed tomography in patients with scapular neck fractures cannot be recommended based on this study. Computed tomography of scapular neck fractures may be useful in selected cases in which intraarticular extension is noted on plain films. PMID- 11782624 TI - Teleradiology in orthopaedic surgery: impact on clinical decision making for acute fracture management. AB - OBJECTIVE: To determine whether teleradiology improved clinical decision making for the treatment of patients with acute fractures. DESIGN: Prospective cohort. SETTING: Level 1 trauma center. PATIENTS: One-hundred eight consecutive patients with 123 acute fractures who visited our Level 1 trauma center, when the first author was the attending orthopedic surgeon on call, and had orthopaedic consultations were included. MAIN OUTCOME MEASURES: In each case, an orthopaedic junior resident performed the emergency department consultation. Radiographs were digitized and electronically transmitted to the attending orthopaedist. Treatment plans were formulated and recorded by the attending surgeon at three different times. The original plan was defined after traditional verbal communication of physical and radiographic findings. A revised plan was defined after the radiographic images were reviewed by the attending surgeon, and the final plan was defined after review of the original radiographs. Two different types of deviations from the original plan were distinguished. Changes in the acute management were defined as any emergency department procedures, emergent operative procedures, or dispositions that were not part of the original plan. Changes in the ultimate management were defined as changes to the original plan that did not affect emergency department treatment, emergent operative procedures, or the disposition of the patient. RESULTS: In twenty-six of the 123 fractures (21 percent), the additional information provided by viewing electronically transmitted images of radiographs changed the acute management or the ultimate management. In none of the 123 cases did subsequent review of original radiographs result in any further changes to the treatment plan. CONCLUSIONS: The routine use of electronically transmitted digitized radiographic images has the potential to improve clinical decision making for the care of patients with acute fractures. PMID- 11782626 TI - Treatment outcome of nonclostridial gas gangrene at a Level 1 trauma center. AB - OBJECTIVE: To evaluate the results of treatment of nonclostridial gas gangrene at a Level 1 trauma center. DESIGN: Retrospective. SETTING: Level 1 trauma center. PATIENTS: Seven patients with nonclostridial gas gangrene were studied. The average age of all patients at the time of admission was 40.3 years (range 14 to 67 years). RESULTS: Three of seven patients had posttraumatic infection, and the remaining four were strongly associated with underlying diseases: diabetes mellitus in three and paraplegia as the result of a spinal cord injury in two. The time of symptom onset was clearly defined in four cases, and the average interval between symptom onset and transfer to our hospitals was six days (range 2 to 10 days). Surgical debridement was performed immediately on admission in six patients (86 percent). A triple antibiotic regimen consisting of penicillin, gentamicin, and clindamycin was used initially in all patients. In three patients, hyperbaric oxygen therapy was also used. The overall mortality rate was 42.9 percent (three of seven patients). In these patients, the interval from onset of symptom to transfer to our hospital was ten days in one patient, which was longer than average, and was not accurately known in the other two patients. CONCLUSION: Nonclostridial gas gangrene is extremely rare but life-threatening. The greatest pitfall for the emergency department physician is failure to suspect it clinically. Aggressive treatment, including surgical debridement and intravenous antibiotics with or without hyperbaric oxygen therapy, must be initiated immediately to minimize morbidity and mortality. PMID- 11782627 TI - Modified tibial nails for treating distal tibia fractures. AB - OBJECTIVE: To determine the biomechanical consequences of cutting one centimeter off the tip of a tibial nail when treating distal tibia fractures with intramedullary nails. DESIGN: Randomized laboratory investigation using matched pairs of cadaveric tibias with osteotomies made to resemble distal tibia fractures extending to four and five centimeters from the tibiotalar joints. INTERVENTION: The smaller (four-centimeter) distal tibias were stabilized using ten-millimeter diameter tibial nails that had been modified by removing the distal one centimeter of the nail. The five-centimeter distal tibias were stabilized with standard ten-millimeter diameter tibial nails. Each tibia was tested in elastic compression, rotation, and compression-bending on a servohydraulic materials testing machine. MAIN OUTCOME MEASUREMENTS: Stiffness was calculated for each type of loading to compare stability of the modified nail construct to that of the standard nail construct. RESULTS: Four-centimeter distal tibia fragments stabilized with modified nails have comparable stiffness in compression and in torsion to five-centimeter distal tibia fragments stabilized with standard tibial nails. The stiffness in compression-bending was surprisingly low in both groups and differed by only 3.7 percent. CONCLUSIONS: Removal of one centimeter from the tip of a tibial nail allows placement of two distal interlocking screws in tibial fractures located four centimeters from the tibiotalar joint. The fixation strength achieved is comparable to that of standard intramedullary nailing of tibial fractures located five centimeters from the tibiotalar joint using two distal interlocking screws. Fixation strength with these distal fractures, however, is not strong enough to resist moderate compression-bending loads. Thus, patients with distal tibia fractures treated with intramedullary nailing must follow weight-bearing restrictions until significant fracture healing occurs to prevent coronal plane malalignment of the fracture. PMID- 11782628 TI - Anatomic assessment of the proper insertion site for a tibial intramedullary nail. AB - OBJECTIVES: To locate the proper insertion point for a tibial intramedullary nail in the coronal plane. DESIGN: Fifty-seven cadaveric lower legs were disarticulated at the knee and ankle and stripped of their soft tissue. Each tibia was nailed in a retrograde fashion through the center of the tibial plafond with a seven-millimeter sharp-tipped rod through the proximal tibia. The exit point of the nail was measured in the coronal plane in relation to the tibial tubercle. RESULTS: Except for one tibia, the intramedullary nail exit point was always located medial to the center of the tibial tubercle with the average being eight millimeters +/- six millimeters medial to the center of the tibial tubercle. Forty-six percent of the nails exited medial to the whole tibial tubercle. CONCLUSIONS: The insertion point of a tibial nail should be over the medial aspect of the tibial tubercle in the coronal plane. Our data supports using a medial or patellar splitting approach for nail insertion. Insertion sites lateral to the tibial tubercle should be avoided. PMID- 11782629 TI - Percutaneous pin placement in the medial calcaneus: is anywhere safe? AB - OBJECTIVE: To redefine the medial calcaneal anatomic safe zone for pin placement with respect to reproducible palpable landmarks. DESIGN: Anatomic study. SETTING: Medical school anatomy laboratory. INTERVENTIONS: Thirty-three fresh-frozen adult cadaveric feet were used. Three palpable anatomic landmarks were identified on each ankle and labeled as Point A (posteroinferior medial calcaneus), Point B (inferior medial malleolus), and Point C (navicular tuberosity). The medial neurovascular bundle was carefully dissected, and the medial calcaneal nerve, the most posterior branch of the lateral plantar nerve, the lateral plantar nerve, the medial plantar nerve, and the posterior tibial artery were identified. These structures were recorded at the point at which they transected a line from Point A to B and from Point A to C. Based on the findings of the first thirty-three feet, two pins were placed percutaneously into the medial calcaneus of ten additional feet. Pin 1 was placed one half the distance from Point A to B. Pin 2 was placed one third the distance from Point A to C. The neurovascular structures were then dissected and identified in relation to the pin position. RESULTS: The medial calcaneal, most posterior branch of the lateral plantar, and lateral plantar nerves are at significant risk for abutting the pins or being directly injured at the margins of these relative safe zones. CONCLUSION: The medial calcaneus provides a small window for safe percutaneous pin placement. Posterior to the halfway point from Point A to B and posterior to the one-third mark from Point A to C remain the relatively safest regions; a more posterior placement in the safe zone is safest. Careful blunt dissection and the use of cannulas may help to avoid neurovascular injury. PMID- 11782630 TI - Change over time of SF-36 functional outcomes for operatively treated unstable ankle fractures. AB - OBJECTIVE: Ankle fractures are one of the most common operatively treated lower extremity fractures. Several studies indicate that patients often have residual effects after this injury. The purpose of this study is to use the SF-36 questionnaire at two times to assess patients' functional recovery and residual effects after operative stabilization of an unstable ankle fracture. DESIGN: Twenty adult patients with an isolated unstable ankle fracture (OTA 44B/C) who had operative stabilization completed an SF-36 questionnaire when they were released from orthopaedic follow-up at approximately four months from injury. These same patients again completed the SF-36 at a longer follow-up, twenty months on average. Both SF-36 scores were compared with U.S. population norms. SETTING: Level II Community Hospital. INTERVENTION: Internal fixation of unstable ankle fractures. MAIN OUTCOME MEASURES: SF-36 questionnaire. RESULTS: Patients had significant improvement (p < 0.5) in all domains of the SF-36 questionnaire at the later follow-up, except for general health, which was unchanged. Patients still had significant differences in SF-36 scores compared with the U.S. population at the time of release from routine follow-up. The scores of all the domains of the SF-36 at the later follow-up were not significantly different from U.S. population norms except for the domain of physical functioning. CONCLUSIONS: This study indicates that patients have significant improvement in functional outcome after release from orthopaedic follow-up but have a residual physical effect at twenty months after injury. These data are important to guide a patient's expectations after this injury and are also important in considering medicolegal and workers' compensation issues. Patients continue to have improvement in function after we have routinely released them from orthopaedic follow-up. Maximal medical improvement appears to be longer than four months from this injury. PMID- 11782631 TI - Quality of life related to fracture displacement among elderly patients with femoral neck fractures treated with internal fixation. AB - OBJECTIVE: To determine differences in outcome between undisplaced (Garden I and II) and displaced (Garden III and IV) femoral neck fractures in elderly patients treated with internal fixation. SETTING: University hospital. DESIGN: Prospective clinical study. PATIENTS: Ninety patients with an acute femoral neck fracture after a fall. The inclusion criteria were age older than sixty-five years, absence of severe cognitive dysfunction, independent living, and unhindered walking capability preoperatively. The mean follow-up was twenty-six months. INTERVENTION: The patients were treated with closed reduction and percutaneous internal fixation with two cannulated screws. MAIN OUTCOME MEASUREMENTS: Fracture healing complications, pain (visual analogue scale), walking capability, activities of daily living, and quality of life according to EuroQol. RESULTS: The rate of fracture healing complications in displaced femoral neck fractures in patients available at the final follow-up was 36 percent compared with 7 percent in patients with undisplaced fractures. The quality of life, according to EuroQol, of patients with uneventfully healed fractures was significantly lower in patients with primarily displaced fractures (0.51) than in patients with undisplaced ones (0.76). CONCLUSION: There was a major difference in outcome on comparing undisplaced and displaced femoral neck fractures in elderly patients treated with internal fixation. The rate of fracture healing complications in patients with undisplaced fractures was low, and patients with healed fractures regained their prefracture quality of life level. The rate of fracture healing complications and reoperations in patients with displaced fractures was high, and even in patients with uneventfully healed fractures, there was a substantial decrease in the quality of life. PMID- 11782632 TI - The relationship between admission hemoglobin level and outcome after hip fracture. AB - OBJECTIVE: To determine the effect of admission hemoglobin level on patient outcome after hip fracture. STUDY DESIGN: Prospective, consecutive. PATIENTS: From July 1991 to June 1997, 395 community-dwelling patients sixty-five years of age or older who had sustained an operatively treated femoral neck or intertrochanteric fracture were prospectively followed up. MAIN OUTCOME MEASUREMENTS: Postoperative complications, in-hospital mortality rate, hospital length of stay, hospital discharge status, place of residence at one year, and mortality and recovery of ambulatory ability and activities of daily living status at three, six, and twelve months. RESULTS: Women with admission hemoglobin levels below 12.0 grams per deciliter and men with admission hemoglobin levels below 13.0 grams per deciliter were classified as anemic. One hundred eighty patients (45.6 percent) were considered anemic on admission. Patients who were anemic were more likely to have an American Society of Anesthesiologists rating of III or IV and have sustained an intertrochanteric fracture. Hospital length of stay and mortality rate at six and twelve months were significantly higher for patients who were anemic on admission. There were no differences in the incidence of postoperative complications, hospital discharge status, place of residence at one year, in-hospital mortality rate, and three-month mortality rate between patients who were and were not anemic on admission. In addition, there were no differences in the recovery of ambulatory ability and of basic and instrumental activities of daily living status at three, six, and twelve months between the two patient groups. CONCLUSIONS: Patients at risk for poor outcomes after hip fracture can be identified by assessing hemoglobin levels at hospital admission. PMID- 11782633 TI - Circumferential pelvic antishock sheeting: a temporary resuscitation aid. AB - Acute traumatic pelvic ring instability causes severe pain and associated hemorrhage. Circumferential pelvic sheeting provides patient comfort and noninvasive, rapid, and temporary pelvic ring stability. A bed sheet is readily available, inexpensive, easily applied around the pelvis, and disposable. PMID- 11782634 TI - Femoral head avulsion fracture with malunion to the acetabulum: a case report. AB - The case of a patient who sustained an avulsion fracture of the femoral head (Pipkin Type I) that was unrecognized is described. The patient was referred to the authors' institution four months after injury, and radiographic studies showed a malunited avulsion fracture of the femoral head to the acetabulum. The patient subsequently went on to an excellent result after surgical debridement. The authors recommend additional radiographic studies in cases to exclude unrecognized fractures where a possible hip subluxation may have occurred. PMID- 11782635 TI - Retrieval of an intact, intraarticular bullet by hip arthroscopy using the lateral approach. AB - A twenty-seven-year-old man sustained a gunshot wound to the left gluteal region. Both plain films and a computed tomography (CT) scan confirmed that the bullet was in the hip joint. Using the lateral approach, the patient underwent hip arthroscopy, and the bullet was removed without difficulty. After surgery, the patient went on to an uneventful recovery. The use of arthroscopy for bullet removal minimized the surgical dissection, avoided an extensive capsulotomy, and reduced the associated risk of injury to the blood supply of the femoral head and osteonecrosis. This report illustrates the application of hip arthroscopy in the removal of retained bullets with minimal associated morbidity and further expands the indications for this procedure. PMID- 11782636 TI - Posteromedial dislocation of the elbow with associated intraarticular entrapment of the lateral epicondyle. AB - Traumatic elbow dislocation is relatively common in adolescents. Most cases occur in a posterolateral direction. Elbow dislocation is often accompanied by fractures, most frequently of the medial epicondyle. The authors report a rare case of posteromedial elbow dislocation and associated fracture of the lateral humeral epicondyle trapped within the joint. PMID- 11782637 TI - Midpalmar space hematoma mimicking compartment syndrome of the hand. AB - A hematoma in the midpalmar space following a crush injury produced the signs and symptoms of compartment syndrome. The clinical presentation, findings at surgery, and likely pathogenesis are discussed. PMID- 11782638 TI - Acute indirect ankle injuries in the adult. 1981. PMID- 11782640 TI - Multiaxis muscle strength in ACL deficient and reconstructed knees: compensatory mechanism. AB - PURPOSE: It is unclear how muscle strength in tibial rotation and knee abduction change following anterior cruciate ligament (ACL) injury and reconstruction. Such strength changes are likely, considering the oblique orientation of the ACL and the constraint provided by the ACL at various tibial rotation and adduction positions. The purposes of this study were to evaluate multiaxis muscle strength in ACL deficient and reconstructed knees and to gain insights into potential compensatory mechanisms adopted by the patients. METHODS: Muscle strength in tibial internal-external rotation, abduction-adduction, and flexion-extension were investigated in 19 chronic ACL deficient, 18 acute ACL deficient, 21 ACL reconstructed, and 23 normal subjects. The strength ratios of flexion/extension, abduction/adduction, and internal/external rotation were determined for each subject and compared across the different populations. RESULTS: The chronic ACL deficient patients showed significantly lower strength ratio in internal/external rotation than that of the normal controls and acute ACL deficient subjects (P = 0.02), indicating a compensatory mechanism developed by the patients to unload the ACL and/or to avoid unstable knee positions. For ACL reconstructed patients, the internal/external rotation strength ratio became closer to their counterparts in normal controls than that of chronic ACL deficient patients, presumably reflecting the reduced need for compensation after reconstruction. Furthermore, compared with strength reduction in knee extension, reductions in tibial rotation and abduction strength following ACL reconstruction were less severe and more easy to recover. CONCLUSION: A better understanding of changes in multiaxis muscle strength and the associated compensatory mechanism will help us evaluate treatment outcome more accurately and develop more effective treatment modalities with focus on muscles that help protect and unload the ACL. PMID- 11782641 TI - Hip muscle imbalance and low back pain in athletes: influence of core strengthening. AB - PURPOSE: The influence of a core-strengthening program on low back pain (LBP) occurrence and hip strength differences were studied in NCAA Division I collegiate athletes. METHODS: In 1998, 1999, and 2000, hip strength was measured during preparticipation physical examinations and occurrence of LBP was monitored throughout the year. Following the 1999-2000 preparticipation physicals, all athletes began participation in a structured core-strengthening program, which emphasized abdominal, paraspinal, and hip extensor strengthening. Incidence of LBP and the relationship with hip muscle imbalance were compared between consecutive academic years. RESULTS: After incorporation of core strengthening, there was no statistically significant change in LBP occurrence. Side-to-side extensor strength between athletes participating in both the 1998-1999 and 1999 2000 physicals were no different. After core strengthening, the right hip extensor was, on average, stronger than that of the left hip extensor (P = 0.0001). More specific gender differences were noted after core strengthening. Using logistic regression, female athletes with weaker left hip abductors had a more significant probability of requiring treatment for LBP (P = 0.009) CONCLUSION: The impact of core strengthening on collegiate athletes has not been previously examined. These results indicated no significant advantage of core strengthening in reducing LBP occurrence, though this may be more a reflection of the small numbers of subjects who actually required treatment. The core program, however, seems to have had a role in modifying hip extensor strength balance. The association between hip strength and future LBP occurrence, observed only in females, may indicate the need for more gender-specific core programs. The need for a larger scale study to examine the impact of core strengthening in collegiate athletes is demonstrated. PMID- 11782642 TI - Resistance exercise and bone turnover in elderly men and women. AB - PURPOSE: This investigation examined the effect of 6 months of high- or low intensity resistance exercise (REX) on bone mineral density (BMD) and biochemical markers of bone turnover in adults aged 60-83 yr. METHODS: Sixty-two men and women (68.4 +/- 6 yr) were stratified for strength and randomly assigned to a control (CON, N = 16), low-intensity (LEX, N = 24), or high-intensity (HEX, N = 22) group. Subjects participated in 6 months of progressive REX training. Subjects trained at either 50% of their one repetition maximum (1-RM) for 13 repetitions (LEX) or 80% of 1-RM for 8 repetitions (HEX) 3 times x wk(-1) for 24 wk. One set each of 12 exercises was performed. 1-RM was measured for eight exercises. BMD was measured for total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry (DXA). Serum levels of bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and pyridinoline cross-links (PYD) were measured. RESULTS: 1-RM significantly increased for all exercises tested for both the HEX and LEX groups (P < and = 0.050). The percent increases in total strength (sum of all eight 1-RMs) were 17.2% and 17.8% for the LEX and HEX groups, respectively. Bone mineral density (BMD) of the femoral neck significantly (P < 0.05) increased by 1.96% for the HEX group. No other significant changes for BMD were found. OC increased by 25.1% and 39.0% for the LEX and HEX groups, respectively (P < 0.05). BAP significantly (P < 0.05) increased 7.1% for the HEX group. CONCLUSION: These data indicate high-intensity REX training was successful for improving BMD of the femoral neck in healthy elderly subjects. Also, these data suggest REX increased bone turnover, which over time may lead to further changes in BMD. PMID- 11782643 TI - Association of physical activity and bone: influence of vitamin D receptor genotype. AB - PURPOSE: The aim of the study was to investigate the interaction between leisure physical activity and a BsmI polymorphism at the vitamin D receptor (VDR) gene on the modulation of bone mineral density (BMD). METHODS: We studied 575 unrelated healthy postmenopausal women. Lumbar spine and femoral neck BMD were measured by dual-energy x-ray absorptiometry (DXA), and results were expressed as age-and weight-adjusted (Z-score). VDR BsmI genotype was determined by polymerase reaction chain on peripheral blood leukocytes. RESULTS: Overall, no significant association was found between the level of leisure physical activity or VDR genotypes and adjusted BMD at both bone sites. However, in active women, there was a trend for an association between VDR genotypes and adjusted BMD at the lumbar spine. Active women, who exercised three times or more a week, carrying the "bb" genotype had a lower BMD at the lumbar spine than active women carrying "BB" genotype (ANOVA; P = 0.04). No significant difference in crude or adjusted BMD at both bone sites was found between VDR genotypes in sedentary or moderately active women. Furthermore, classification of women according to the median-age of the sample (63.1 yr) revealed a significant interaction between the level of leisure physical activity and VDR genotype on adjusted lumbar spine BMD in the older active postmenopausal women (N = 137). Older active women carrying the "bb" genotype showed a lower adjusted BMD at the lumbar spine compared with active women carrying the "BB" genotype (P = 0.007). CONCLUSION: These results suggested that gene-environment interactions such as leisure physical activity and VDR genotype may play a role in maintaining the BMD at the lumbar spine in active postmenopausal women, especially in older active women. PMID- 11782644 TI - The prevention of shin splints in sports: a systematic review of literature. AB - PURPOSE: To review the published and unpublished evidence regarding risk factors associated with shin splints, assess the effectiveness of prevention strategies, and offer evidence-based recommendations to coaches, athletes, and researchers. METHODS: We searched electronic data bases without language restriction, identified citations from reference sections of research papers retrieved, contacted experts in the field, and searched the Cochrane Collaboration. Of the 199 citations identified, we emphasized results of the four reports that compared methods to prevent shin splints. We assessed the methodologic quality of these reports by using a standardized instrument. RESULTS: The use of shock-absorbent insoles, foam heel pads, heel cord stretching, alternative footwear, as well as graduated running programs among military recruits have undergone assessment in controlled trials. There is no strong support for any of these interventions, and each of the four controlled trials is limited methodologically. Median quality scores in these four studies ranged from 29 to 47, and serious flaws in study design, control of bias, and statistical methods were identified. CONCLUSION: Our review yielded little objective evidence to support widespread use of any existing interventions to prevent shin splints. The most encouraging evidence for effective prevention of shin splints involves the use of shock-absorbing insoles. However, serious flaws in study design and implementation constrain the work in this field thus far. A rigorously implemented research program is critically needed to address this common sports medicine problem. PMID- 11782645 TI - Effect of mouthguards on dental injuries and concussions in college basketball. AB - PURPOSE: Dental injuries can be permanent and disfiguring. They are also universally expensive to treat. Many dentists, sports physicians, and athletic trainers recommend mouthguards for athletes participating in certain competitive sports, including men's college basketball, because of a common perception that mouthguards afford protection from dental injuries, and even some concussions. However, there are few reliable reports of the incidence of dental injuries and concussions in men's college basketball, and good evidence that mouthguards reduce the risk of these injuries in this population of athletes is notably lacking. This study prospectively recorded dental injuries and concussions among 50 men's Division I college basketball teams during one competitive season, then compared injury rates between mouthguard users and nonusers. METHODS: During the 1999 to 2000 basketball season, athletic trainers from 50 men's Division I college basketball programs used an Internet Web site to submit weekly reports of the number of athlete exposures, mouthguard users, concussions, oral soft tissue injuries, dental injuries, and dentist referrals. RESULTS: Response rate was 86%. There were 70,936 athlete exposures. Athletes using custom-fitted mouthguards accounted for 8663 exposures. Injury rates were expressed as number of injuries per 1000 athlete exposures. There were no significant differences between mouthguard users and nonusers in rates of concussions (0.35 vs 0.55) or oral soft tissue injuries (0.69 vs 1.06). Mouthguard users had significantly lower rates of dental injuries (0.12 vs 0.67; P < 0.05) and dentist referrals (0.00 vs 0.72; P < 0.05) than nonusers. CONCLUSION: Custom-fitted mouthguards do not significantly affect rates of concussions or oral soft tissue injuries, but can significantly reduce the morbidity and expense resulting from dental injuries in men's Division I college basketball. PMID- 11782646 TI - Soft tissue thermodynamics before, during, and after cold pack therapy. AB - BACKGROUND: Cold packs are commonly used by clinicians, trainers, and others, often as an interim treatment for many acute conditions, but the extent of temperature change associated with this form of treatment remains poorly understood. METHODS: In 16 healthy male and female volunteers aged 25.4 +/- 3.6 yr, we monitored skin temperature, and recorded the temperature of the quadriceps muscle at 1, 2, and 3 cm depths below the skin, before, during, and after 20 min of cold pack treatment. RESULTS: The results revealed a slight rise in temperature at all four levels during the 5 min pretreatment period, but significant temperature falls at the skin and 1 cm levels beginning from 8 min of treatment (P < 0.001). There was no significant change in tissue temperature at the 2.0 cm or 3.0 cm depths throughout treatment. However, after treatment, cutaneous temperature and the temperature at 1.0 cm depth rose rapidly, returning to baseline levels at variable intersubject times. As these superficial temperatures rose, there were concurrent falls in the temperatures at the 2.0 cm and 3.0 cm levels. Thus, the deeper tissues lost heat (cooled) simultaneously as the superficial tissues rewarmed; to the extent that 40 min after treatment, the deeper levels were cooler than the cutaneous and 1.0 cm levels. CONCLUSION: 1) Cold pack therapy produces significant temperature falls in cutaneous and subcutaneous superficial tissues without directly changing the temperature of tissues at or more than 2.0 cm below the skin; and 2) the temperature gradients of both layers of tissue reverses after treatment, indicating that the deep tissue beneath is at least one of the sources of heat used to rewarm the cooled superficial tissue. The latter finding underscores the importance of the hemodynamic interchange between superficial and deep tissues, and offers an explanation for the reduction of pain, muscle spasm, and edema observed with cold therapy in several clinical situations. PMID- 11782647 TI - Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. AB - PURPOSE: Previous studies in chronic fatigue syndrome (CFS) have reported reductions in maximal oxygen uptake (VO(2max)), yet often the testing procedures have not followed accepted guidelines, and gender data have been pooled. The present study was undertaken to reevaluate exercise capacity in CFS patients by using "gold standard" maximal exercise testing methodology and stratifying results on a gender basis. METHODS: Sixteen male and 17 female CFS patients and their gender-, age-, and mass-matched sedentary controls performed incremental exercise to volitional exhaustion on a stationary cycle ergometer while selected cardiorespiratory and metabolic variables were measured. RESULTS: VO(2max) in male CFS patients was not different from control values (CFS: 40.5 +/- 6.7; controls: 43.3 +/- 8.6; mL x kg(-1) x min(-1)) and was 96.3 +/- 17.9% of the age predicted value, indicating no functional aerobic impairment (3.7 +/- 17.9%). In female CFS patients, VO(2max) was lower than control values (CFS: 30.0 +/- 4.7; controls: 34.2 +/- 5.6; mL x kg(-1) x min(-1), P = 0.002), but controls were higher than the age-predicted value (112.6 +/- 15.4%, P = 0.008) whereas the CFS patients were 101.2 +/- 20.4%, indicating no functional aerobic impairment (-1.2 +/- 20.4%). Maximal heart rate (HR(max)) in male CFS patients was lower than their matched controls (CFS: 184 +/- 10; controls: 192 +/- 12; beats x min(-1); P = 0.016) but was 99.1 +/- 5.5% of their age-predicted value. In female CFS patients, HR(max) was not different from controls (CFS: 183 +/- 11; controls: 186 +/- 10; beats x min(-1)) and was 98.9 +/- 5.1% of the age-predicted value. The VO(2) at the lactate threshold (LT) in each gender group, whether expressed in mL x kg(-1) x min(-1) or as a percentage of VO(2max), was not different between CFS patients and controls. CONCLUSIONS: In contrast to most previous reports, the present study found that VO(2max), HR(max), and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age. PMID- 11782648 TI - Implementation of the Ottawa ankle rule in a university sports medicine center. AB - PURPOSE: The Ottawa ankle rule (OAR) is a clinical decision rule used in emergency departments to identify which patients with acute ankle/midfoot injury require radiography. The purpose of this study was to implement the OAR, with a modification to improve the specificity for identifying malleolar fractures (the "Buffalo rule"), in a sports medicine center and measure impact on physician practice and cost savings. METHODS: All pediatric and adult patients presenting to a university sports medicine walk-in clinic with acute (< or = 10 d old) ankle/midfoot injury had the rule applied by primary care providers. Exclusion criteria included pregnancy, isolated skin injury, > 10 d since injury, second evaluation for same injury, obvious deformity of ankle or foot, or altered sensorium. RESULTS: In 217 patients (mean age, 23.3 +/- 8.5 yr; range, 10-64 yr) there were 24 clinically significant (i.e., nonavulsion) fractures (fracture rate 3.7% per year for 3 yr), all of which were identified by the rule (100% sensitivity). In 193 patients with malleolar pain, the sensitivity for malleolar fracture (with 95% confidence intervals) was 100% (78-100%) and specificity was 45% (43-46%). In 24 patients with midfoot pain, sensitivity was 100% (65-100%) and specificity was 35% (21-49%). Thirty-five percent of radiographic series (76 of 217) were foregone for a cost savings of almost $6000. One hundred percent follow-up on those patients for whom x-rays were obtained found no missed fractures and they were subjectively satisfied with their care. CONCLUSION: The OAR reduced radiography in acute ankle/midfoot injury and saved money in relatively younger patients in the outpatient sports urgent care setting without missing any clinically significant fractures. The specificity of the Buffalo malleolar rule in the present implementation study, however, was not a significant improvement over the OAR malleolar rule. Widespread application of the OAR could save substantial resources without compromising quality of care. PMID- 11782649 TI - Concentric or eccentric training effect on eccentric exercise-induced muscle damage. AB - PURPOSE: The purpose of this study was to compare changes in muscle damage indicators following 24 maximal eccentric actions of the elbow flexors (Max-ECC) between the arms that had been previously trained either eccentrically or concentrically for 8 wk. METHODS: Fifteen subjects performed three sets of 10 repetitions of eccentric training (ECC-T) with one arm and concentric training (CON-T) with the other arm once a week for 8 wk using a dumbbell representing 50% of maximal isometric force of the elbow flexors (MIF) determined at the elbow joint of 90 degrees (1.57 rad). The dumbbell was lowered from a flexed (50 degrees, 0.87 rad) to an extended elbow position (180 degrees, 3.14 rad) in 3 s for ECC-T, and lifted from the extended to the flexed position in 3 s for CON-T. Max-ECC was performed 4 wk after CON-T and 6 wk after ECC-T. Changes in MIF, range of motion (ROM), upper arm circumference (CIR), muscle soreness (SOR), and plasma creatine kinase (CK) activity were compared between the ECC-T and CON-T arms. RESULTS: The first ECC-T session produced larger decreases in MIF and ROM, and larger increases in CIR and SOR compared with CON-T. CK increased significantly (P < 0.01) and peaked 4 d after the first training session, but did not increase in the following sessions. All measures changed significantly (P < 0.01) following Max-ECC; however, the changes were not significantly different between ECC-T and CON-T arms. CONCLUSION: These results showed that ECC-T did not mitigate the magnitude of muscle damage more than CON-T, and CON-T did not exacerbate muscle damage. PMID- 11782650 TI - The response of rabbit patellar tendons after autologous blood injection. AB - PURPOSE: Blood is a rich source of growth factors that can stimulate fibrocyte migration and help induce neovascular ingrowth. These properties may be able to stimulate a healing response in chronic degeneration of a tendon (tendonosis). The purpose of this study was to assess the biomechanical and histological effects of autologous blood injection on animal tendons. METHODS: New Zealand white rabbit left side patellar tendons were injected with 0.15 cc of autologous blood. We then compared the mechanical properties and histology to the normal right patellar tendon at 6 and 12 wk. RESULTS: At 6 and 12 wk after the injection, there were no differences in the histology compared with normal tendon tissue, and there were no significant changes in tendon stiffness. Biomechanically, the tendons were not damaged at 6 wk after the injection. By 12 wk, tendons that were injected with blood were significantly (P < 0.014) stronger. CONCLUSION: We found that injecting blood directly into normal tendons appears safe. Further evaluation of this technique would appear indicated. PMID- 11782651 TI - Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study. AB - PURPOSE: To investigate the influences of menopause, hormone replacement, and endurance exercise training on cardiovascular hemodynamics and oxygen uptake parameters during exercise in women. METHODS: Subjects were 338 premenopausal women, 29 postmenopausal women taking hormone replacement, and 28 postmenopausal women not taking hormone replacement, all enrolled in the HERITAGE Family Study. Hemodynamic and oxygen uptake data were gathered on a cycle ergometer at 50 watts (W), 60% peak oxygen uptake, and at peak exercise, both before and after a 20-wk regimen of endurance exercise training on a cycle ergometer. RESULTS: Systolic blood pressure (SBP) during peak exercise was found to be an average of 14 mm Hg less in postmenopausal women receiving hormones than in those not receiving hormones. Furthermore, menopause was associated with a 26.2 mm Hg higher SBP at 50 W power output, which remained physiologically significant after adjustment for age. At 50 W, postmenopausal women not taking hormones showed a 13.8 mm Hg greater training-induced reduction in SBP than those taking hormones. CONCLUSION: It was concluded that hormone replacement may be associated with a vasodilatory reserve at high exercise intensities and that endurance exercise training elicits favorable hemodynamic and oxygen uptake adaptations during exercise that are, in most instances, independent of menstrual status or hormone replacement. PMID- 11782652 TI - Adaptations to short-term high-fat diet persist during exercise despite high carbohydrate availability. AB - PURPOSE: Five days of a high-fat diet produce metabolic adaptations that increase the rate of fat oxidation during prolonged exercise. We investigated whether enhanced rates of fat oxidation during submaximal exercise after 5 d of a high fat diet would persist in the face of increased carbohydrate (CHO) availability before and during exercise. METHODS: Eight well-trained subjects consumed either a high-CHO (9.3 g x kg(-1) x d(-1) CHO, 1.1 g x kg(-1) x d(-1) fat; HCHO) or an isoenergetic high-fat diet (2.5 g x kg(-1) x d(-1) CHO, 4.3 g x kg(-1) x d(-1) fat; FAT-adapt) for 5 d followed by a high-CHO diet and rest on day 6. On day 7, performance testing (2 h steady-state (SS) cycling at 70% peak O(2) uptake [VO(2peak)] + time trial [TT]) of 7 kJ x kg(-1)) was undertaken after a CHO breakfast (CHO 2 g x kg(-1)) and intake of CHO during cycling (0.8 g x kg(-1) x h(-1)). RESULTS: FAT-adapt reduced respiratory exchange ratio (RER) values before and during cycling at 70% VO(2peak); RER was restored by 1 d CHO and CHO intake during cycling (0.90 +/- 0.01, 0.80 +/- 0.01, 0.91 +/- 0.01, for days 1, 6, and 7, respectively). RER values were higher with HCHO (0.90 +/- 0.01, 0.88 +/- 0.01 (HCHO > FAT-adapt, P < 0.05), 0.95 +/- 0.01 (HCHO > FAT-adapt, P < 0.05)). On day 7, fat oxidation remained elevated (73 +/- 4 g vs 45 +/- 3 g, P < 0.05), whereas CHO oxidation was reduced (354 +/- 11 g vs 419 +/- 13 g, P < 0.05) throughout SS in FAT-adapt versus HCHO. TT performance was similar for both trials (25.53 +/- 0.67 min vs 25.45 +/- 0.96 min, NS). CONCLUSION: Adaptations to a short-term high fat diet persisted in the face of high CHO availability before and during exercise, but failed to confer a performance advantage during a TT lasting approximately 25 min undertaken after 2 h of submaximal cycling. PMID- 11782653 TI - Determination of the exercise intensity that elicits maximal fat oxidation. AB - PURPOSE: The aim of this study was to develop a test protocol to determine the exercise intensity at which fat oxidation rate is maximal (Fat(max)). METHOD: Eighteen moderately trained cyclists performed a graded exercise test to exhaustion, with 5-min stages and 35-W increments (GE(35/5)). In addition, four to six continuous prolonged exercise tests (CE) at constant work rates, corresponding to the work rates of the GE test, were performed on separate days. The duration of each test was chosen so that all trials would result in an equal energy expenditure. Seven other subjects performed three different GE tests to exhaustion. The test protocols differed in stage duration and in increment size. Fat oxidation was measured using indirect calorimetry. RESULTS: No significant differences were found in Fat(max) determined with the GE(35/5), the average fat oxidation of the CE tests, or fat oxidation measured during the first 5 min of the CE tests (56 +/- 3, 64 +/- 3, 58 +/- 3%VO(2max), respectively). Results of the GE(35/5) protocol were used to construct an exercise intensity versus fat oxidation curve for each individual. Fat(max) was equivalent to 64 +/- 4%VO(2max) and 74 +/- 3%HR(max). The Fat(max) zone (range of intensities with fat oxidation rates within 10% of the peak rate) was located between 55 +/- 3 and 72 +/- 4%VO(2max). The contribution of fat oxidation to energy expenditure became negligible above 89 +/- 3%VO(2max) (92 +/- 1%HR(max)). When stage duration was reduced from 5 to 3 min or when increment size was reduced from 35 to 20 W, no significant differences were found in Fat(max), Fat(min), or the Fat(max) zone. CONCLUSION: It is concluded that a protocol with 3-min stages and 35-W increments in work rate can be used to determine Fat(max). Fat oxidation rates are high over a large range of intensities; however, at exercise intensities above Fat(max), fat oxidation rates drop markedly. PMID- 11782654 TI - Ventilatory and gas exchange responses during heavy constant work-rate exercise. AB - PURPOSE: At constant work-rates below the gas exchange threshold (VO(2 theta)), VO(2) normally achieves steady-state values within 3 min, whereas at heavier work rates, VO(2) may continue to rise. The VO(2) response to heavy exercise can be described by a three-exponential model with the slow phase usually commencing 2-3 min after the onset of exercise. The aim of our study was to estimate precisely the VO(2), VCO(2), VE and f(C) required for above-VO(2 theta) exercise from the relationship of the specific variable to work-rate below VO(2 theta) and to compare this with the actual value achieved. METHODS: Nine cyclists performed five constant work-rates of 8 min duration, four below VO(2 theta) (40, 80, 120, 160 W) and one midway between VO(2 theta) and VO(2max) (295 +/- 34 W). The VO(2), VCO(2), VE and f(C) were averaged for the final 2 min of each below-VO(2 theta) test and were found to be linear with respect to work-rate (average r2 >0.95). Variables for the above-VO(2 theta) work-rate were predicted by extrapolation and compared with the actual measured values at the end of the exercise bout. RESULTS: VO(2) exceeded the predicted value by 0.48 +/- 0.21 L x min(-1) (12.4 +/ 5.1%), VCO(2) by 0.78 +/- 0.26 L x min(-1) (23.2 +/- 7.2%), VE by 40.3 +/- 16.3 L x min(-1) (51.0 +/- 23.1%), and f(C) by 12.2 +/- 12.5 beats x min(-1) (8.8 +/- 9.3%), all P < 0.0001 except f(C) P < 0.02, paired t-test. The point at which VO(2) during above-VO(2 theta) exercise exceeded the predicted value (145.7 +/- 64.9 s) agreed with the point at which the slow component of VO(2) began, as determined by nonlinear regression analysis (131.5 +/- 44.3 s, P = NS, ANOVA). CONCLUSION: There is an excessive metabolic response to heavy exercise over and above that predicted by extrapolation from light-moderate exercise and this excess VO(2) approximates on average to the slow phase of a three-compartment exponential model. PMID- 11782655 TI - Vertical jump coordination: fatigue effects. AB - PURPOSE: The aim of this study was to investigate the segmental coordination of vertical jumps under fatigue of the knee extensor and flexor muscles. METHODS: Eleven healthy and active subjects performed maximal vertical jumps with and without fatigue, which was imposed by requesting the subjects to extend/flex their knees continuously in a weight machine, until they could not lift a load corresponding to approximately 50% of their body weight. Knee extensor and flexor isokinetic peak torques were also measured before and after fatigue. Video, ground reaction forces, and electromyographic data were collected simultaneously and used to provide several variables of the jumps. RESULTS: Fatiguing the knee flexor muscles did not reduce the height of the jumps or induce changes in the kinematic, kinetic, and electromyographic profiles. Knee extensor fatigue caused the subjects to adjust several variables of the movement, in which the peak joint angular velocity, peak joint net moment, and power around the knee were reduced and occurred earlier in comparison with the nonfatigued jumps. The electromyographic data analyses indicated that the countermovement jumps were performed similarly, i.e., a single strategy was used, irrespective of which muscle group (extensor or flexors) or the changes imposed on the muscle force generating characteristics (fatigue or nonfatigue). The subjects executed the movements as if they scaled a robust template motor program, which guided the movement execution in all jump conditions. It was speculated that training programs designed to improve jump height performance should avoid severe fatigue levels, which may cause the subjects to learn and adopt a nonoptimal and nonspecific coordination solution. CONCLUSION: It was suggested that the neural input used in the fatigued condition did not constitute an optimal solution and may have played a role in decreasing maximal jump height achievement. PMID- 11782656 TI - Alteration of the position sense at the ankle induced by muscular fatigue in humans. AB - PURPOSE: The purpose of this study was to investigate how an isometric exhaustion test affects the position sense at the ankle using an active matching task. METHODS: Eight male subjects with a mean age 24.6 yr participated in the study. Subjects' ability to match the right ankle with the position of the left reference ankle position-determined using signed and absolute errors and variability-was investigated. This task was realized for four ankle angular values (in degrees), two in dorsiflexion (P(-20), P(-10)) and two in plantarflexion (P(20), P(10)) and for two experimental conditions: 1) normal and 2) fatigue. Muscular fatigue was induced in tibialis anterior (TA) of the right leg (ankle dorsiflexor) by using an isometric test. Subjects were instructed to maintain a workload of 70% of their maximal voluntary contraction in series of 40 s. RESULTS: With fatigue, subjects produced ankle movements characterized by greater absolute errors for movements of large amplitude in dorsiflexion and for movements of small amplitude in plantarflexion. In addition, using a "worst-case scenario" analysis, results showed that errors were significantly greater than the normal functioning range for 20 degrees dorsiflexion and 10 degrees plantarflexion positioning. CONCLUSIONS: The acuity of the position sense at the ankle is reduced subsequent to a fatigue protocol. The influence and the potential deleterious effects of muscular fatigue on position sense are discussed. PMID- 11782657 TI - Foot strike patterns after obstacle clearance during running. AB - PURPOSE: Running over obstacles of sufficient height requires heel strike (HS) runners to make a transition in landing strategy to a forefoot (FF) strike, resulting in similar ground reaction force patterns to those observed while landing from a jump. Identification of the biomechanical variables that distinguish between the landing strategies may offer some insight into the reasons that the transition occurs. The purpose of this study was to investigate the difference in foot strike patterns and kinetic parameters of heel strike runners between level running and running over obstacles of various heights. METHODS: Ten heel strike subjects ran at their self-selected pace under seven different conditions: unperturbed running (no obstacle) and over obstacles of six different heights (10%, 12.5%, 15%, 17.5%, 20%, and 22.5% of their standing height). The obstacle was placed directly before a Kistler force platform. Repeated measures ANOVAs were performed on the subject means of selected kinetic parameters. RESULTS: The statistical analysis revealed significant differences (P < 0.004) for all of the parameters analyzed. The evaluation of the center of pressure and the ground reaction forces indicated that the foot strike patterns were affected by the increased obstacle height. Between the 12.5% and 15% obstacle conditions, the group response changed from a heel strike to a forefoot strike pattern. CONCLUSIONS: At height > 15%, the pattern was more closely related to the foot strike patterns found in jumping activities. This strategy change may represent a gait transition effected as a mechanism to protect against increased impact forces. Greater involvement of the ankle and the calf muscles could have assisted in attenuating the increased impact forces while maintaining speed after clearing the obstacle. PMID- 11782658 TI - A three-dimensional shank-foot model to determine the foot motion during landings. AB - PURPOSE: The purposes of this study were a) to develop a model of the foot capable of describing the foot motion during dynamic movements and b) to study the influence of different mats on foot motion during landing in gymnastics. METHODS: Six female gymnasts (height: 1.63 +/- 0.04 m, weight: 58.21 +/- 3.46 kg) participated in this study. All six gymnasts carried out barefoot landings, falling from 80 and 115 cm onto three mats each with a different stiffness (hard, medium, and soft). Three synchronized digital high-speed video cameras (250 Hz) captured the motion of the left shank and foot. At the same time, the reaction forces between mat and foot at the forefoot and rearfoot were measured by two instrumented insoles (Paromed, 1000 Hz). The kinematics of the tibiotalar, talonavicular, and calcaneocuboid joints were examined. The lower leg and the foot were modeled by means of a multi-body system, comprising seven rigid bodies. For each joint, two joint coordinate systems attached on each of the connected segments were defined. RESULTS: The mat stiffness did not show any influence on the maximal reaction forces or on the kinematics of the tibiotalar joint. For the soft mat, higher maximal eversion angles at the talonavicular and the calcaneocuboid joints were measured. CONCLUSIONS: The relative motion between forefoot and rearfoot was influenced by changing mat stiffness. Therefore, the construction of the mat influenced the motion of the foot. The observation of only the tibiotalar joint is not enough when studying the influence of different mats on foot motion. The functional benefit of the mechanical advantages of a soft mat (higher energy absorption) includes a decrease in stability. The surface of the landing mat should, therefore, be reinforced by a stabilizing mechanism. PMID- 11782659 TI - Children's OMNI Scale of Perceived Exertion: walking/running evaluation. AB - PURPOSE: The Children's OMNI-walk/run Scale of Perceived Exertion (category range, 0-10) was evaluated using male and female children (6-13 yr of age) during a treadmill graded exercise test. METHODS: A cross-sectional, perceptual estimation paradigm using a walking/running test protocol was administered. Oxygen uptake (VO(2), mL x min(-1)), %VO(2max), ventilation (VE, L x min(-1)), respiratory rate (RR, breaths x min(-1)), respiratory exchange ratio (RER), heart rate (HR, beats x min(-1)), V(E)/VO(2) ratio, and ratings of perceived exertion (RPE) measurements were made every minute throughout the test. RESULTS: Significant correlations were found between OMNI-walk/run Scale RPE responses and VO(2), %VO(2max), HR, V(E)/VO(2) ratio, and RR throughout the maximal treadmill exercise test. The strongest correlations were found between RPE and %VO(2max) (r = 0.41-0.60, P < 0.001) and HR (r = 0.26-0.52, P < 0.01). CONCLUSION: The psychophysiological responses provide validity evidence for use of the Children's OMNI-walk/run Scale over a wide range of exercise intensities during both walking and running. PMID- 11782660 TI - Predicted maximal aerobic power in youth is related to age, gender, and ethnicity. AB - PURPOSE: To determine the effects of age, gender, and ethnicity on the predicted aerobic power of youth as they age from 8 to 16 yr. METHODS: The sample was a multicohort group of 2540 African Americans (N = 543) and Caucasians (N = 1997), 1279 (50.4%) girls and 1261 (49.6%) boys. Heights, weights, and sum of skin folds (triceps + subscapular) were measured. Aerobic power ((p)VO(2max)), expressed in relative (mL x kg(-1) x min(-1)) or absolute (L x min(-1)) terms, was predicted from a three-stage cycle ergometry test. RESULTS: Quadratic mixed-model analysis indicated that boys had higher relative and absolute (p)VO(2max) than the girls (P = 0.0004). The African American subjects had a higher absolute (p)VO(2max) (L x min(-1)) than the Caucasians, but their relative (p)VO(2max) was lower than the Caucasians (P = 0.031). Finally, age had a significant effect on (p)VO(2max) (P = 0.0001). The absolute (p)VO(2max) of the girls increased 9%.yr(-1) until age 14; but their relative (p)VO(2max) declined approximately 1.2 mL x kg(-1) x min(-1) x yr(-1). The absolute (p)VO(2max) for the boys increased yearly by approximately 14% from ages 8 to 16 yr, but the relative (p)VO(2max) of the African American males was stable from ages 8 to 11, then dropped, and stabilized again between ages 12 and 16 yr. The relative (p)VO(2max) of the Caucasian boys declined from ages 8 to 10, but then increased slightly from age 12 to 16 yr. In addition, the interactions of age and gender, and age squared and gender were significant (P < 0.02). CONCLUSION: These data indicate that although absolute (p)VO(2max) (L x min(-1)) increases from age 8 to 16 yr, relative (p)VO(2max) (mL x kg(-1) x min( 1)) declines. The decline appears to be related to increased fat mass. Similarly, the higher relative (p)VO(2max) (mL x kg(-1) x min(-1)) of the Caucasian youth compared with the African American youth was related to lower weights and skin folds of the Caucasian youth. PMID- 11782661 TI - VO(2) reserve and the minimal intensity for improving cardiorespiratory fitness. AB - PURPOSE: The American College of Sports Medicine has stated that aerobic training needs to occur at a minimum threshold intensity of 50% VO(2max) for most healthy adults and at 40% VO(2max) for those with a very low initial fitness. Recently, the concept of VO(2) reserve (%VO(2R), i.e., a percentage of the difference between maximum and resting VO(2)) has been introduced for prescribing exercise intensity. This analysis was designed to determine the threshold intensity for improving cardiorespiratory fitness expressed as %VO(2R) units. METHODS: Previous studies in healthy subjects (N = 18) that evaluated the results of training at low-to-moderate intensities (i.e., < or = 60% VO(2max)) were identified. The original studies described the intensity of exercise variously as %VO(2max), %HRR, %HR(max), or as a specific HR value. In each case, the intensity was translated into %VO(2R) units. RESULTS: Exercise training intensities below approximately 45% VO(2R) were consistently ineffective at increasing VO(2max) in studies that used subjects with mean initial VO(2max) values > 40 mL x min(-1) x kg(-1). In studies using subjects with mean initial VO(2max) values < 40 mL x min(-1) x kg(-1), no intensity was found to be ineffective. For this latter group of subjects, the lowest intensities examined were approximately 30% VO(2R). CONCLUSION: Although evidence for a threshold intensity was not strong, this analysis of training studies supports the use of 45% VO(2R) as a minimal effective training intensity for higher fit subjects and 30% VO(2R) for lower fit subjects. PMID- 11782662 TI - Occupational physical activity is related to physical fitness in young workers. AB - PURPOSE: We evaluated the association between occupational physical activity and fitness in young workers, taking into account leisure-time physical activity, body size, and smoking. METHODS: The study population comprised 2188 men and 1987 women, members of the Northern Finland birth cohort 1966, who participated in the 1997-1998 follow-up survey and were employed at the time of the survey. Cardiorespiratory fitness was measured by a 4-min step test and muscular fitness by tests of maximal isometric handgrip and isometric trunk extension. Information on occupational and leisure-time physical activity and smoking was obtained by questionnaire, and body height and weight were measured during medical examination. The data were analyzed by analysis of variance and Cox regression. RESULTS: Men doing heavy physical work scored better in cardiorespiratory fitness, handgrip strength, and trunk muscle endurance than men doing lighter work; the finding for cardiorespiratory fitness was similar in women. The associations were independent of leisure-time physical activity, body weight and height, and smoking. CONCLUSION: A positive association was found between heavy physical work and a high level of fitness in young workers. Due to limitations of the study setting, causality cannot be asserted, but a training effect of heavy work would not seem unreasonable. Previous studies have suggested a reversal of the positive effect of heavy work on fitness with advancing age. Therefore, regular monitoring of workers' fitness at an early phase is justified to enable assessment of workers' capacity for heavy jobs and any possible need for fitness improving activities. PMID- 11782663 TI - Knee and ankle joint stiffness in sprint running. AB - INTRODUCTION: Stiffness has often been considered as a regulated property of the neuromuscular system. The purpose of this study was to examine the ankle and knee joint stiffness regulation during sprint running. METHODS: Ten male sprinters ran at the constant relative speeds of 70, 80, 90, and 100% over a force platform, and ground reaction forces, kinematic, and EMG parameters were collected. RESULTS: The results indicated that with increasing running speed the average joint stiffness (change in joint moment divided by change in joint angle) was constant (7 N x m x deg(-1)) in the ankle joint and increased from 17 to 24 N x m x deg(-1) (P < 0.01) in the knee joint. CONCLUSION: The observed constant ankle joint stiffness may depend on (constant) tendon stiffness because of its dominating role in triceps surae muscle-tendon unit. Thus, we conclude that in sprint running the spring-like behavior of the leg might be adjusted by changing the stiffness of the knee joint. However, in complicated motor task, such as sprint running, ankle and knee joint stiffness might be controlled by the individual mechanical and neural properties. PMID- 11782664 TI - Bone density in female elite gymnasts: impact of muscle strength and sex hormones. AB - PURPOSE: The aim of this study was to investigate BMD in Danish female elite gymnasts and the relationships to maximal muscle strength, sex hormone concentrations, and menstrual status. METHODS: Six artistic gymnasts, five rhythmic gymnasts, and six controls aged 15-20 yr served as subjects. BMD (g x cm(-2)) of lumbar spine, proximal femur, distal radius, and whole body were measured by dual-energy x-ray absorptiometry (DXA) scanning. Maximal muscle strength (Nm) was measured in isokinetic trunk extension, trunk flexion, and knee extension. Serum concentrations of estrogen and progesterone in follicular and luteal phases were evaluated. RESULTS: Three out of six artistic gymnasts had amenorrhea, and two artistic and one rhythmic gymnast experienced oligomenorrhea. BMD in artistic gymnasts was greater than controls (24-45%, P < 0.05) in all sites except whole body. BMD in rhythmic gymnasts was greater than controls (4 26%, P < 0.05) in all sites except distal radius. In gymnasts, BMD correlated to both maximal muscle strength (0.60 < r < 0.85, P < 0.05) and serum progesterone (0.65 < r < 0.75, P < 0.05). CONCLUSION: In spite of oligomenorrhea or amenorrhea, it is possible for female gymnasts to maintain a high BMD in both the axial (L2-L4) and appendicular skeleton. The correlations between BMD and maximal muscle strength and progesterone concentration in gymnasts may indicate that within the same athletic group, progesterone concentration has a permissive role in bone formation, thus affecting the positive impact of muscle strength. PMID- 11782665 TI - Re: Bell, DG, I Jacobs, and K Ellerington. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc.33:1399-1403, 2001. PMID- 11782667 TI - Detection of gsp somatic mutation through direct sequencing of heteroduplex alleles disclosed by denaturing gradient gel electrophoresis. AB - BACKGROUND: The identification of somatic mutations in tissues is often difficult when the number of normal alleles in the tissue far exceeds the number of mutant ones. We found that the identification of gsp mutation was not possible by direct sequencing and present a new approach that improves the identification of gsp somatic mutations. MATERIAL/METHODS: Genomic DNA was extracted from frozen tissue of a human ovarian stromal Leydig cell tumor. Exons 8 and 9 of the Gsa gene were amplified by PCR and despite the abnormal migration pattern at this first DGGE, direct sequencing of the PCR product did not reveal mutations, probably due to the small amount of mutant alleles. To improve this amount, the PCR products were re-amplified using as template the excised products of the mutant homoduplex and heteroduplex bands obtained at the first DGGE. RESULTS: This approach resulted in the enhancing of the mutant homoduplex bands whereas the heteroduplex bands remained unchanged at the second DGGE. Direct sequencing of the second round PCR clearly identified the mutation R201C in the ovarian Leydig cell tumor. CONCLUSIONS: We have demonstrated a relatively rapid, convenient and reliable method to improve gsp somatic mutation detection combining a second DGGE of the PCR products obtained from the heteroduplexes and mutant homoduplex bands disclosed in a first DGGE followed by direct sequencing. PMID- 11782666 TI - NOC/oFQ activates PKC and generates superoxide to impair hypotensive cerebrovasodilation after hypoxia/ischemia. AB - BACKGROUND: Previous studies have observed that hypotensive pial artery dilation was blunted following global cerebral ischemia in the piglet. In unrelated studies, superoxide (O-2) contributed to impaired hypotensive cerebrovasodilation following traumatic brain injury in the rat while the opioid nociceptin/orphanin FQ (NOC/oFQ) generated O-2 via activation of protein kinase C in the piglet. This study determined the contribution of NOC/oFQ, PKC activation and O-2 generation in hypoxic ischemic hypotensive cerebrovasodilation impairment. MATERIAL/METHODS: Anesthetized newborn pigs equipped with a closed cranial window were used. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia, via inhalation of nitrogen, decreased PO2 to 34I3 mmHg. RESULTS: Topical NOC/oFQ (10 10M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44I2%) induced pial artery dilation (33I1 vs 19I2%). Coadministration of the PKC inhibitor chelerythrine (10-7M) or the O-2 scavenger polyethylene glycol superoxide dismutase and catalase (SODCAT) with NOC/oFQ (10 10M) partially prevented hypotensive pial dilation impairment (34I2 vs 28I1% for SODCAT). Hypotensive pial artery dilation was blunted by hypoxia/ischemia but such dilation was partially protected by the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH2 (10-6M), chelerythine or SODCAT (34I1 vs 7I2 vs 21I2% for sham, H/I and H/I + SODCAT, respectively). CONCLUSIONS: These data show that PKC activation and generation of O-2 contributes to hypoxia/ischemia impairment of hypotensive pial artery dilation. These data suggest that NOC/oFQ activates PKC and generates O-2 to impair hypotensive cerebrovasodilation after hypoxia/ischemia. PMID- 11782668 TI - Mechanism of the contractile effects of galantide and Galanin(1-14) [alpha aminobutyric acid]scyliorhinin-I in rat isolated fundus strips. AB - BACKGROUND: The study was undertaken to establish the pharmacological basis of the stimulatory activity of galantide (M15) and galanin(1-14)-(a-aminobutyric acid8-[Abu8])scyliorhinin-I [Scy-I] in gastric smooth muscle. MATERIAL/METHODS: Isotonic contractions of the isolated, longitudinal rat gastric fundus strips were recorded. RESULTS: Galanin, galanin(1-15)-NH2, M15 and galanin(1-14) [Abu8]Scy-I elicited concentration-dependent contractions. Their EC50s equaled 12.95, 174, 70.06 and 187 nM respectively. Hill's coefficients for galanin and galanin(1-15)-NH2 were not different from unity, indicating an interaction of one peptide molecule with one receptor according to the principles of classical receptor theory. Hill's coefficients were 0.73 and 1.56 for M15 and galanin (1 14)-[Abu8]Scy-I, respectively, a value significantly different from unity. Cold storage denervation, tetrodotoxin-TTX (1 mM), spantide (100 mM) and NK1-3 receptor antagonists SR140333, 48968, 142801 (up to 10 mM) notably diminished M15, galanin(1-14)-[Abu8]Scy-I, SP(5-11) and [Abu8]-Scy-I evoked contractions without affecting activities of galanin and galanin(1-15)-NH2. Additionally, cross-desensitization experiments attenuated activity of M15 and galanin(1-14) [Abu8]Scy-I without any noticeable action on galanin or galanin(1-15)-NH2. CONCLUSIONS: The action of chimeric peptides on the smooth muscle of the rat gastrointestinal tract depended not only on the myogenic interaction of those peptides with galanin binding sites, but also on the activation of tachykinin receptors or the release of endogenous mediators from the presynaptic terminals. PMID- 11782669 TI - Use of secretin in the treatment of childhood autism. AB - The paper presents current views concerning childhood autism. The authors present the concepts of etiology of this disorder, emphasizing the role of negative psychical stimuli in early childhood and the role of mother's contact with the child. Organic factors, including genetic background, developmental abnormalities of the nervous system, teratogenic factors and perinatal traumas are also taken into consideration. The role of metabolic factors and enterohormones, particularly those belonging to the secretin group and their effect on the function of the gastrointestinal tract and central nervous system is emphasized. We discuss signs which may be indicative of first symptoms of autism in different age groups. A typical symptom of autism is no development of speech, observed from infancy, taking the form of complete mutism at later stages. It has been emphasized that most pathologic symptoms result from altered perception of external stimuli, which arouse fear and anxiety. Autistic patients may suffer from gastrointestinal tract disturbances such as abdominal pains and diarrhea. Methods used hitherto in the therapy of childhood autism, mainly by psychologists and psychiatrists, as well as some attempts of pharmacological treatment, are presented. The structure and function of secretin, as well as its effects on the motor and secretory function of the stomach and the exocrine function of the pancreas are discussed. The role of secretin in diagnostic tests, among others in the diagnosis of gastrinoma, is emphasized. We also present the history of the application of secretin in the therapy of childhood autism. PMID- 11782670 TI - Soluble cytokine receptors in renal vasculitis and lupus nephritis. AB - BACKGROUND: The activation of various cytokines, e.g. TNFalpha, IL-1 and/or IL-6, may play an important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). The systemic effect of these cytokines may be modulated by their circulating soluble receptors. The plasma levels of cytokine receptors may thus also be markers of the activation of these cytokines. MATERIAL/METHODS: The plasma levels of TNFalpha, its soluble receptor p75 (sTNF-RII), IL-6, and the soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 patients with ANCA positive renal vasculitis (12 active - ANCA-A, 7 in remission ANCA-R), 9 patients with active lupus nephritis (LN), and 5 healthy subjects. RESULTS: Patients with LN had increased plasma levels of TNFalpha, sTNF-RII, IL-6 and sIL-6R in comparison with controls. Patients with ANCA-A also had increased plasma levels of TNFalpha, sTNF-RII and sIL-6R in comparison with controls, but the increase in the plasma level of IL-6 was not statistically significant, due to the large standard deviation. Patients with ANCA-R had increased plasma levels of sTNF-RII in comparison to controls, but the plasma levels of TNFalpha were significantly lower in ANCA-R than in ANCA-A. While the ratio of TNFalpha to sTNF-RII was significantly lower in all groups of patients than in the controls, the ratio of IL-6 to sIL-6R was significantly increased only in LN in comparison to controls. CONCLUSIONS: While increased plasma levels of TNFalpha may be a nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are also increased in patients with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may inhibit the systemic effects of TNFalpha, but may also prolong the half-life of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is much less pronounced than that of sTNF-RII and cannot effectively block the systemic effects of IL-6. PMID- 11782672 TI - Usefulness of immunohistochemical testing and electron microscopy in the diagnosis of embryonal rhabdomyosarcoma. AB - BACKGROUND: This article presents the results of histological, immunohistochemical, and ultrastructural examinations of embryonal rhabdomyosarcoma. MATERIAL/METHODS: 20 tumors were tested histologically, 13 immunohistochemically, and 5 under electron microscopy. RESULTS: We found that in cases when the entire tumor or large specimens were obtained for estimation, it was possible by examining many areas of the neoplasm to establish a diagnosis on the basis of testing paraffined sections, routinely HE stained. Our evaluation of the value of certain additional histological methods indicated only slight diagnostic usefulness for tumors of this kind. Among the immunohistochemical methods we evaluated, the desmin assay had the greatest practical applicability, due to the fact that this antigen is also expressed in highly immature cells; in second place was myoglobin. Differences are pointed out in the results obtained by assaying myoglobin using DAB and the DAKO kit. Ultrastructural examinations revealed myofilaments of myosin and actin in all types of cells, including immature cells. Particular attention is drawn to the possibility of using material fixed in formalin for ultrastructural examination. The preservation of intact myofilaments in material prepared in this way constitutes an essential diagnostic aid. CONCLUSIONS: In diagnosing embryonal rhabdomyosarcoma the most useful examination, apart from histological examination, is electron microscopy, followed by immunomorphological examination. PMID- 11782671 TI - Electron microscope investigation of the role of Chlamydia sp. in the process of rebuilding the arterial wall. Neoangiogenesis in atherosclerotic plaques in human cervical artery walls. AB - BACKGROUND: The inflammatory process has an essential impact on the development of atherosclerosis. Three mechanisms are mentioned: 1) possibility of direct development of Chlamydia infection in the vicinity of the blood vessel wall; 2) impact of persistent or recurrrent Chlamydia infection on the increased blood concentration of risk factors for atherosclerosis; 3) an autoimmunological reaction. MATERIAL/METHODS: Electron microscope examinations were performed on specimens from atherosclerotic lesions of the interior cervical arteries, collected from patients who had undergone endarterectomy. The material came from 8 patients (age from 58 to 72). The specimens were fixed for electron microscopy, and after dehydration were immersed in Spurr resin. Ultrathin slices were examined under a transmission electron microscope. RESULTS: In the successive tested layers nearest the lumen of the vessel we found erythrocytic elements, fibrin, and lipid membranes. In deeper layers there were lymphocytic cells, monocytes, and macrophages loaded with phagocyted lipid material. Under this layer we found in some specimens a coating which had undergone mineralization: calcium structures and cholesterol were overlaid on a proteoglycanate base. Smooth muscles cells had undergone the heaviest proliferation among the cells on artery wall. In the tested material we detected diversified morphological forms of Chlamydia sp. Particular attention should be drawn to the appearance of very young vessel forms, which suggests a process of angiogenesis in the atherosclerotic plaques. CONCLUSIONS: We found that one of the pathogens that may lead to atherosclerotic lesions is Chlamydia sp. The process of atherogenesis in cervical arteries is accompanied by angiogenetic processes. PMID- 11782673 TI - Activity of serum lipase [EC 3.1.1.3] and the diversity of serum lipid profile in psoriasis. AB - BACKGROUND: In the course of psoriasis the loss of scales from the skin surface is observed. This may be related to lipid disorders in epidermis and in blood serum. The aim of the study was to find out if serum lipid profile disturbances occur in psoriatic patients. MATERIAL/METHODS: We studied 26 male and 15 female normolipidemic psoriatic patients, and 29 male and 28 female healthy normolipidemic volunteers. The concentrations of serum pancreatic lipase, total cholesterol, HDL cholesterol, LDL cholesterol, total phospholipids, HDL phospholipids, LDL phospholipids and triglycerides were measured with enzymatic methods. RESULTS: The study of male patients demonstrated a statistically significant decrease in HDL cholesterol concentration and statistically significant increase in triglyceride concentration. In psoriatic females, we observed a statistically significant decrease in HDL cholesterol concentration, a statistically significant decrease in HDL phospholipid concentration, and a statistically significant increase in pancreatic lipase concentration. In addition, the pancreatic lipase concentration increased insignificantly in the male group. We found lipid profile disturbances in the groups of psoriatic patients, in comparison with the age-, sex-, and BMI-matched control groups. CONCLUSIONS: The obtained results suggest the necessity of careful administration of medicines to psoriatic patients suffering from systemic diseases and treated with drugs affecting lipid metabolism. PMID- 11782674 TI - An evaluation of the impact of supplementation with antioxidant vitamins on oxidation stress parameters in children with chronic recurrent gastroduodenitis. AB - BACKGROUND: The purpose of our research was to evaluate the impact of supplementation with antioxidative vitamins in children with chronic recurrent gastroduodenitis on the concentration of malon-dialdehyde (MDA) in plasma and erythrocytes, and on activity of the antioxidant enzymes: dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). MATERIAL/METHODS: We studied 19 children (age from 13 to 16), diagnosed with chronic recurrent gastroduodenitis. The concentration of MDA was measured by Buege and Aust method, while the antioxidant enzyme activity was measured before and after a two-month course of supplementation with vitamins C and E: SOD by the Misra and Fridovich method, CAT by the Bears and Seizer method, and GSH-Px by the Paglia and Valentine method. RESULTS: The average concentration of MDA in erythrocytes in the studied children was significantly higher (38.59 nM/gHb) than in control group (24.07 nM/gHb), but after supplementation was significantly reduced (p<0.05). The average SOD activity in the experimental group was significantly lower both before (885 U/gHb) and after supplementation (923.3 U/gHb) than in the control group (1240 U/gHb). The activity of the remaining enzymes did not differ significantly in experimental and control groups. CONCLUSIONS: The increased erythrocyte concentration of MDA in children with chronic recurrent gastroduodenitis may point to the generation of active forms of oxygen due to the low activity of the anti-oxidant enzyme SOD. Supplementation with the antioxidant vitamins C and E in children with a low antioxidant potential and chronic recurrent gastroduodenitis reduces the generation of free oxygen radicals. PMID- 11782675 TI - Evaluation of bladder instability in children with recurrent urinary tract infections. AB - BACKGROUND: Impairment in the functions of the lower urinary tract can be the cause of recurrent urinary tract infections (UTI) and vesicoureteral reflux (VUR) in children. The purpose of our research was to evaluate the frequency of occurrence of bladder instability in children with UTI. MATERIAL/METHODS: The research involved 114 children (21 boys, 93 girls), ranging in age from 5 to 16. Group I consisted of 61 children with a history of recurrent UTI, while Group II included 53 children with recurrent UTI and VUR. Urodynamic tests (uroflowmetry and cystometry) were done on all the children, while in selected cases profilometry was also performed, using a Duet apparatus (Dantec Medical A/S). RESULTS: Abnormal functioning of the lower urinary tract was found in 45 children (74%) from Group I and 44 children (84%) from Group II. The most common dysfunction was instability of the detrusor muscle, which was found in 52 children (45%), including 23 (38%) from Group I and 29 (55%) from Group II. In 19 children detrusor instability was accompanied by reduced bladder volume, and in 8 cases there was a lack of detrusor-sphincter coordination. In both groups ca. 20% of the children did not present with symptoms indicating urination dysfunctions. Ca. 80% reported various symptoms, of which the most common were nocturnal wetting and urinary urgency. In half of the children from Group I and one-fourth of the children from Group II there were several co-occurring symptoms: nocturnal and diurnal wetting, pollakiruria, and urinary urgency, or all three symptoms simultaneously. CONCLUSIONS: The most common disturbance of lower urinary tract functioning in these children with recurrent UTI was instability of the detrusor muscle, which occurred more often in children with VUR. PMID- 11782676 TI - Acute renal failure in patients with rhabdomyolysis. AB - BACKGROUND: Rhabdomyolysis is a relatively rare, not always diagnosed cause of acute renal failure (ARF). This fact motivated us to present the results of ARF treatment in the course of this polyetiological clinical syndrome. MATERIAL/METHODS: The analysis was performed on 84 patients (6 F, 78 M) ranging in age from 18 to 82 years (mean 46.5), in whom rhabdomyolysis was diagnosed based on clinical manifestation and laboratory test results (CPK, GTP, GOT, LDH). RESULTS: The most frequent cause of rhabdomyolysis was alcoholic intoxication (41 patients), often accompanied by hypothermia (15 patients) or trauma (30 patients). Isolated trauma was found in 30 patients, epileptic seizure in 5, and physical exercise in 1 case. In 17 patients, besides alcohol consumption, trauma or epileptic seizure, the use of tranquilizers, anticonvulsants, or narcotic drugs was additionally noted. 78 patients developed ARF requiring dialysis therapy; 49 patients recovered, 5 required maintenance dialysis, and 30 died. CONCLUSIONS: During the initial phase of ARF in the course of rhabdomyolysis dynamic increases in serum urea and creatinine were observed, as well as a tendency to hyperkalemia. The treatment results and mortality rate in our study group were primarily influenced by the patients' general condition at admission, as well as the extent of organ damage caused by the primary etiological factor. Favorable treatment results were obtained especially in those patients who were hospitalized in a nephrological center, while the worst outcomes were noted in those patients dialyzed in intensive care units, most with multiple trauma. PMID- 11782677 TI - The influence of controlled hypotension on splanchnic mucosal perfusion using gastric tonometry in patients undergoing resection of meningioma. AB - BACKGROUND: The aim of our research was to evaluate the influence of general anesthesia with controlled nitroglycerin-induced hypotension on splanchnic mucosal perfusion using gastric tonometry. MATERIAL/METHODS: In six patients (1 female, 5 males, median age 46 years, range 32-62) undergoing elective resection of meningiomas, measurements of gastric mucosal perfusion were taken by nasogastric tonometry. Controlled hypotension was initiated after craniotomy and terminated prior to hemostasis procedures. The mean arterial blood pressure (MAP) was maintained 25-30% below initial parameters during controlled hypotension. The adequacy of perfusion was defined by the intramucosal pH (pHi) and the difference between arterial and intramucosal pH (pHGAP). All parameters were analyzed before the induction of controlled hypotension, after the 1st, 2nd, and 3rd hour, and 1 hour after the termination of controlled hypotension. RESULTS: The MAP decreased during controlled hypotension by ca. 26.5% (min. 21.1%; max 31.6%). The lower MAP was accompanied by a statistically significant increase in heart rate. A significant increase from baseline in regional prCO2 was seen after the 1st, 2nd, and 3rd hour of controlled hypotension. Intramucosal pH values decreased significantly during the same period, from 7.428+/-0.032 to 7.372+/-0.015. Despite these statistically significant differences during controlled hypotension, the pHi values were always greater than 7.35, and the pHGAP values were lower than 0.05, which were recognized as being within the normal range. CONCLUSIONS: Controlled hypotension allows accurate evaluation of the blood flow quality at the level of microcirculation. Mild controlled hypotension slightly alters splanchnic mucosal perfusion, but does not lead to ischemia and hypoxia in tissues. PMID- 11782678 TI - Prevalence of cryoglobulinemia in patients with chronic HCV infection. AB - BACKGROUND: The purpose of our research was to determine the prevalence of cryoglobulins in patients with chronic hepatitis C (CHC) at different levels of activity and stage of fibrosis and to identify their association with the extrahepatic clinical manifestations. MATERIAL/METHODS: 87 patients with CHC were investigated for the presence of cryoglobulins. Cryocrit was measured by the Weiner method. AntiHCV, HCV RNR, conventional biochemical tests and liver biopsy were also performed. RESULTS: Cryoglobulins were found in a total of 44 patients: 16 from Group I, 11 from Group II, and 17 from Group III. A low level of cryoglobulinemia (Cg) (cryocritL2%) was detected in 16 patients: 9 from Group I, 3 from Group II, and 4 from Group III. Moreover, a high Cg (cryocrit >5-10%) or very high Cg (cryocrit >10%) was found in a total of 13 patients: 1 patient from Group I, 3 from Group II, and 9 from Group III. Cryo positivity was found in 5 patients with F 1-2, in 13 with F 2-3, in 4 with F 3-4, and in 17 with F 4. CONCLUSIONS: Our findings confirmed the high prevalence of Cg in CHC patients in Lithuania, a clear association between Cg and the stage of fibrosis, the higher prevalence of Cg in cirrhotic patients, and the occurrence of several typical extrahepatic manifestations. The impact of Cg on the course of chronic hepatitis C is not clearly understood; therefore, further studies are needed to clarify this issue. PMID- 11782679 TI - Comparative study of early Lyme disease: Erythema migrans in New York State and Northeastern Poland. AB - BACKGROUND: The objective was to compare the clinical features of early local Lyme Disease: Erythema Migrans (EM) between two highly endemic areas: New York State and Northeastern Poland. Study was based on self reporting questionnaires, physical examination, and laboratory results. MATERIAL/METHODS: Group I (n=27) consisted of citizens from New York State presenting with EM, referred to the study by their physicians. Group II (n=25) consisted of patients treated as outpatients in 1998-1999 at the Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Poland. The diagnosis of EM was based on patient history and clinical picture. RESULTS: Depending on the immune reaction of the host, the clinical picture is variable. The initial symptoms range from discrete to strongly expressed. The inflammatory reaction at the site of tick-bite seems to be milder in Europe than in North America, which is reflected in the prevalence of the annular form of rash and milder expression of general symptoms. Mild or absent general symptoms and the prevalence of the annular over homogenous form are observed in those areas of Europe where Ixodes ricinus is the main vector. In the endemic area of New York State, where Ixodes scapularis mainly occurs, uniform EM with flu-like symptoms is more common. CONCLUSIONS: There are distinct differences in the typical clinical pictures between the two separated endemic areas of New York State and Northeastern Poland, due to different vectors (saliva components?), bacterial genospecies, likely intermediate hosts and climatic differences. Familiarity with the presenting form of the disease can be very important, especially for primary care physicians. PMID- 11782680 TI - Active and passive executive function disorder subsequent to closed-head injury. AB - BACKGROUND: Executive dysfunction is one of the most destructive sequelae of closed head injuries (CHI), often impeding or even preventing the patient's return to normal functioning. On the basis of extensive clinical testing of patients with neurobehavioral disturbances resulting from CHI, the authors propose a new typology of executive dysfunction based on the primary behavioral distinction between active ('acting without thinking') and passive ('thinking without acting') forms of executive function disorder. MATERIAL/METHODS: Two patients were selected for detailed presentation. Both present with mild to moderate motor and cognitive symptoms resulting from closed head injury. The medical histories of the two patients are similar (educated professionals, mid 40s, married with children, injuries suffered in a traffic accident, 2 months in coma) except for the location of focal injuries. RESULTS: Despite considerable progress in rehabilitation, the extent of functional disorder is disproportionately large in comparison to the degree of objective disability measured by standard instruments. It is suggested that the reason for this disparity lies in executive dysfunction. In particular, a model for executive functioning will be presented to explain why and how selective destruction of particular anatomical/functional components leads to the behavioral consequences known as 'executive dysfunction'. CONCLUSIONS: Executive dysfunction is a distinct clinical syndrome which occurs in at least two distinguishable varieties, active and passive. PMID- 11782681 TI - The 'CARFEM' vascular index as a predictor of coronary atherosclerosis. AB - BACKGROUND: The purpose of the study was detection of coronary atherosclerosis and identification of persons at risk by means of non-invasive examination of the carotid and peripheral arteries. MATERIAL/METHODS: Investigation of 366 patients: 229 males and 137 females divided into groups according to age and the severity of the coronary atherosclerotic lesions. Only patients with a coronary stenosis of more than 90%, who needed angioplasty or coronary bypass surgery, were included. Group I consisted of patients with normal coronary arteries; Group II, critical one-vessel disease; Group III, two-vessel disease; Group IV, critical three-vessel disease. By means of a vascular duplex scan we measured bilaterally the intima-media thickness of the posterior wall of the common carotid artery. In order to provide a more accurate estimation of the total atherosclerotic burden we have created the 'CARFEM' index (combination index of intima media thickness of carotid artery and total wall thickness of the superficial femoral artery). RESULTS: The anthropometric data were identical among the different groups. There are statistically highly significantly differences in the intima-media thickness of the common carotid artery when patients with normal coronary arteries are compared with patients with three-vessel coronary disease. By calculating the 'CARFEM' index not only we can differentiate between patients with normal coronary arteries and patients with critical three-vessel disease, but there are also ways to differentiate between different subgroups and to assess possible one vessel, two-vessel or three-vessel coronary artery disease. CONCLUSIONS: The determination of the intima-media thickness of the common carotid artery clearly enables us to detect possible coronary atherosclerosis and to predict its severity in a non-invasive way. The combined assessment of the carotid and the femoral arterial walls permits us to make a distinction between the different subgroups, divided according to the severity of the underlying coronary atherosclerosis. PMID- 11782682 TI - Evaluation of the usefulness of the ELISA method for detection of enterovirus antibodies in serum samples of patients with myocarditis. AB - BACKGROUND: Enteroviruses are among the etiological factors in myocarditis. In the majority of cases it is impossible to obtain a direct confirmation of the presence of the virus, and typologically specific methods are of limited applicability, due both to the number of enteroviruses that can cause myocarditis, and to the serological cross reactions among them. The goal of our research was to determine the usability of the ELISA test and the complement fixation reaction (CFR) in diagnostic testing of the serum of patients with myocarditis. MATERIAL/METHODS: The research material consisted of 117 serum samples collected from patients with myocarditis. In all these samples we measured the concentration of IgG and IgM enterovirus antibodies using the ELISA method, and the height of the titer using the CFR method. RESULTS: The presence of IgM antibodies is a confirmation of current infection. A positive result was obtained for 61% of the patients. On the other hand, if one accepts as confirmation of infection a titer significantly different from the level observed in the healthy population, namely > or =16 for CFR and > or =11 for ELISA-IgG (cf. positive results of 33% for CFR and 18.8% for ELISA IgG in our patients), the results may be disproportional. If one assumes as a test criterion a significant increase in titer, the presence of infection was confirmed in 28.5% of cases for CFR and 62% for ELISA-IgG. CONCLUSIONS: An analysis of the results obtained here justify the conclusion that neither the height of the CFR titer nor the concentration of IgG antibodies constitutes a clear confirmation of infection, if the criterion of evaluation is based on a measure in a single serum sample. In this case it is necessary to test for a significant increase in the titer. The use of the average titer for the population at large to evaluate results leads to both false positives and false negatives. Testing for IgM antibodies in a single serum sample is a faster method which confirms the current presence of infection. Our results indicate that the ELISA test can be used to diagnose myocarditis, since it is more sensitive and faster than CFR, and allows for the differentiation of antibody classes. PMID- 11782683 TI - Prediction of the biomechanical properties of cancellous bone using ultrasound velocity and bone mineral density--an in vitro study. AB - BACKGROUND: Recent experimental studies have suggested that the combination of DXA (dual energy X-ray absorptiometry) and ultrasound (US) measurements could improve the prediction of bone strength. The aim of this study was to investigate the ability of bone density and US velocity, measured by the phalangeal US system, to predict the Young's modulus and strength of cancellous bone. MATERIAL/METHODS: 35 cubes of bovine cancellous bone from the distal radii were prepared using a diamond cutting saw. The US velocity (Speed of Sound - SoS [m/s]) was measured for the three orthogonal directions (proximal-distal - PD; anterior-posterior - AP; medial-lateral - ML) using a DBM Sonic 1200 device (Igea, Italy). Bone mineral density (BMD [g/cm2]) was measured by DXA, as well as the apparent volumetric BMD (v-BMD [g/cm3], as the ratio of BMD to sample thickness). Young's modulus (E[MPa]) and ultimate strength (s[MPa]) were measured in the PD and AP directions by the uniaxial compressive test. RESULTS: The SoS and biomechanical parameters were significantly higher (p<0.0001) for the PD direction than for horizontal directions. In the PD direction, SoS, BMD and v-BMD correlated significantly with E (r=0.79-0.84, p<0.001) and s (r=0.68-0.80, p<0.01). In the AP direction, SoS and v-BMD correlated significantly (r=0.75 0.77, p<0.05) and BMD correlated almost significantly (r=0.66, p=0.05) with s, whereas their correlations with E were nonsignificant. In the PD direction, the predictive value of SoS or bone density alone for E and s was generally weaker than in the case of the combination of SoS with BMD or v-BMD (63-70% and 46-64% vs. 75-79% and 59-64%, respectively), as was also the case for the AP s (43-60% vs. 66-70%). CONCLUSIONS: The knowledge of both the US velocity and bone density improves the prediction of the biomechanical properties of cancellous bone. PMID- 11782684 TI - An assessment of the effectiveness of magnetic resonance imaging in delayed sequences after administration of Gd-DTPA contrast in the detection of metastatic lesions in the brain. AB - BACKGROUND: Advances in oncology in recent years have made it possible to undertake radical interventions even in advanced cases. Local treatment, surgical or radiosurgical, is applied ever more frequently in cases of metastases to the brain. This requires accurate determination of the number and location of metastases by means of imaging techniques. The goal of our research was to establish whether the use of sequences delayed by 20-30 minutes after gadolinium injection improves the number of metastatic lesions detected in the brain by MRI. MATERIAL/METHODS: Twenty-eight patients were studied, ranging in age from 24 to 72 years, diagnosed with malignant tumors and suspected metastases to the brain. MRI examinations were performed with a 2T unit in SE T1 immediately after i.v. administration of a 0.1 mmol/kg dose of gadolinium, and again 20-30 minutes after contrast injection; both sequences were done in axial projection in layers identical as in the SE T1 sequence made before gadolinium injection. The focal lesions were counted and classified by size. The number of detected lesions was calculated in each group, comparing early and late phases after contrast injection. RESULTS: The number of all nodules found in the delayed sequences was significantly higher in comparison to the early phase after gadolinium injection. CONCLUSIONS: Delayed sequence should be used to supplement basic sequences in the diagnosis of malignant metastases to the brain in selected oncological cases. PMID- 11782685 TI - Comparative study of cefaclor AF vs. cefuroxime axetil in acute exacerbations of chronic bronchitis. AB - BACKGROUND: Acute exacerbations of chronic bronchitis (AECB) are the most common complication of chronic bronchitis. The majority of AECB are caused by infection. The choice of appropriate antibacterial therapy for AECB is becoming more difficult and is usually empirically. Cefaclor and cefuroxime are used for ambulatory treatment of AECB. MATERIAL/METHODS: This multicenter, randomized, single blind study was undertaken in order to compare efficacy and safety of cefaclor AF (500 mg BID) and cefuroxime axetil (250 mg BID) in 10 days treatment of ambulatory patients with AECB. 170 adults were enrolled into the study. Clinical responses were assessed on 17th-24th day after randomization. RESULTS: Both antibiotics had high over 97% effectiveness in the treatment of AECB. There was statistically significant 1.7 times higher rate of patients with cough release after cefaclor treatment compared to cefuroxime (p<0.03). There was a significantly 2.25 higher rate of patients with AECB symptoms release like: increasing dyspnea, sputum volume and sputum purulence or cough in cefaclor group compared to cefuroxime (p<0.0187). Both treatments resulted in significant improvement of pulmonary peak expiratory flow (PEF). There were no differences between the rates of gastrointestinal and other side effects in both groups. CONCLUSIONS: 1. Cefaclor and cefuroxime have similar high efficacy and safety in 10 days treatment of patients with AECB. 2. Cefaclor treatment significantly higher 2.25 times reduces the rate of principle symptoms of AECB compared to cefuroxime. 3. Both antibiotics treatment significantly increase PEF, with higher tendency observed in after cefaclor treatment. PMID- 11782686 TI - Detecting the replication of the hepatitis B virus using the ImmunoMax technique following treatment with interferon-alpha in children with chronic hepatitis. AB - BACKGROUND: Children with HBV in Poland are treated with preparations of interferon-alpha (IFN-alpha). The continuing lack of complete response to this type of anti-viral therapy remains to be explained. The application of cell biology techniques to identify the viral components in situ makes it possible to clarify the association between the distribution of the virus and morphological injury to the liver, the immune response of the host, and clinical symptoms in the natural course of infection. Our study was intended to evaluate HBV expression in liver biopsies taken an average of two years after completion of IFN-a therapy in 10 children with serological markers of persistent HBV infection. MATERIAL/METHODS: For the immunocytochemical detection of HBcAg and for the hybridocytochemical detection of HBV-DNA, the avidin-biotin-peroxidase (ABC) technique was employed, as well as classical in situ hybridization, both additionally amplified using the ImmunoMax technique. HBcAg and HBV-DNA levels were estimated using a semiquantitative technique. RESULTS: Our study demonstrated persistent active replication of HBV in the liver in all examined children. A mixed pattern of HBcAg localization prevailed (noted in cell nuclei, cytoplasm and cell membranes) with a somewhat lower proportion of involved cells and a more evident membrane localization of HBcAg, as compared to results obtained before treatment. HBV-DNA was observed in the cytoplasm of a fraction of hepatocytes similar to that noted before therapy. CONCLUSIONS: The ImmunoMax technique was found to be highly suitable for in situ monitoring of HBV replication after termination of IFN-a treatment. Children with focal distribution of HBcAg and HBV-DNA have the potential for earlier eradication of the virus from their livers. PMID- 11782687 TI - Chronic mesenteric ischemia: diagnosis and treatment with balloon angioplasty and stenting. AB - BACKGROUND: The goal of our research was to evaluate the efficacy of endovascular treatment in stenosis of the superior mesenteric artery and the celiac trunk. MATERIAL/METHODS: During the period 1996-2001, 6 patients (1 woman, 5 men, ages 46 to 73) were referred to our department with abdominal angina. Angiograms were performed in order to establish the reasons. All these patients presented with postprandial abdominal pain and weight loss. Angiography showed stenosis in the superior mesenteric artery in 2 patients, in the celiac trunk in 1 patient, and in both vessels in 3 patients. Typical balloon angioplasty (PTA) was performed with a balloon catheter, 5-8 mm in diameter, inflated up to 18 atm. If more than 30% stenosis remained after PTA, the patient was referred for stenting. RESULTS: In 5 of the 6 patients (83%) PTA was successful. In one patient (17%) with poor results from PTA, a Perflex stent (diameter 7 mm) was implanted in the superior mesenteric artery. The follow-up protocol included clinical and Doppler ultrasonographic examination at 6, 12, and 18 months after surgery. A good clinical and ultrasound outcome was found in 6 patients at 6 and 12 months, and in 4 patients at 18 months. CONCLUSIONS: Balloon angioplasty and stent placement seem to be efficient and safe methods of treatment for abdominal angina in stenosis of the superior mesenteric artery and celiac trunk. PMID- 11782688 TI - Tonal nitric oxide and health--a free radical and a scavenger of free radicals. AB - Basal/tonal nitric oxide (NO) production helps maintain particular microenvironments, i.e., vascular. Besides NO's function in controlling the activation state of various tissues such as immune cells, its presence appears to modulate other free radical levels, i.e., H2O2, in these same tissues and indeed these processes may be one and the same. Thus, by being a free radical, along with the ability to scavenge other free radicals, NO is placed in a pivotal regulatory position. We surmise that in the absence of adequate NO release other free radicals may go 'unchecked' and, therefore, initiate tissue damage. Furthermore, under these circumstances, proinflammatory events will occur due to heightened cell sensitivity and a diminished control of NF-kappaB. In an excess situation, and one without an appropriate circumstance, i.e., microbial action, NO may become the harmful agent. Hence, balancing basal NO production in body compartments may represent a fundamental process in maintaining general, long term health. PMID- 11782689 TI - Markers of inflammation and coronary artery disease. AB - Many recent experimental and clinical studies have provided evidence for the presence of inflammation in atherosclerotic lesions. Ongoing inflammatory reactions within coronary atherosclerotic plaques are increasingly thought to be crucial determinants of the clinical course of patients with coronary artery disease (CAD). These facts lead to a search for reliable markers reflecting the inflammatory process in the atherosclerotic plaques. Circulating markers may consist of cytokines directly released from inflammatory cells present in the plaques and tissues exposed to recurrent ischemia as well as other reactants produced in response to these cytokines such as adhesion molecules and acute phase proteins. Recent studies suggest that markers of inflammation may reflect different aspects of the atherothrombotic process at different points in the continuum of acute coronary syndromes, have a potential role for the prediction of risk for developing CAD, and may correlate with severity and future risk for CAD. In spite of these findings, the clinical utility of measuring these markers is limited by the availability of reproducible diagnostic test assays. In addition, it remains to be determined whether markers of inflammation actually have a causal relation with cardiovascular disease, or simply reflect the underlying disease process. Such determination becomes important with the potential use of these markers in targeting preventive therapies. Therefore, further well-designed prospective evaluation of each of these markers is needed before their use in routine practice. PMID- 11782690 TI - Thrombolysis research--new objectives after a shift of accent. AB - The methods of increasing the efficacy of thrombolysis under clinical and experimental conditions are have been discussed in the light of analysis of current tendencies in the investigation and development of thrombolytic and adjunctive therapy. Analysis of the data obtained in the search for novel plasminogen activators for thrombolytic enzyme therapy has shown a decrease and depletion of this search. The reserves for further increase in thrombolysis efficiency have been notified. Special attention is paid to the purposes, realms and problems of adjunctive therapy, which is a promising breakthrough area in the effort of increasing the efficacy of thrombolysis. PMID- 11782691 TI - Religious sensitivity pitted against the need to know: autopsy of Jewish children in Israel. AB - BACKGROUND: The aim of the study was to compare autopsy findings with antemortem findings in children who died in a pediatric intensive care unit. MATERIAL/METHODS: Consecutive series of patients who died in the pediatric intensive care unit during 2-year period were used. The study was conducted as a retrospective chart review at community, regional-referral, university-affiliated tertiary medical center of 1200 bed in Israel. RESULTS: Permission was given to perform autopsies on only 10 children (23.8%, mean age 85.7 months) out of the 42 who died during the study period. The mean length of stay in the pediatric intensive care unit prior to death was 13.3 days. Cardiac or hemato-oncologic diseases comprised the major pre-admission diagnoses. The autopsy revealed a major finding that, if known before death, would have altered clinical management in 50% of the patients: pneumonia, pneumonitis as well as intestinal perforation or necrosis. No correlation was found between patient length of stay in the intensive care unit and the autopsy disclosed information. CONCLUSIONS: Our findings support the importance of autopsy assessment in the pediatric intensive care setup. We believe that postmortem examination is also essential for improving the quality of pediatric patient care. PMID- 11782692 TI - Brain imaging: can it help select patients for carotid surgery? PMID- 11782693 TI - Extraperitoneal approach reduces intestinal and renal dysfunction in elective abdominal aortic aneurysm repair. AB - BACKGROUND: Intestinal mucosal barrier dysfunction observed in patients undergoing transperitoneal abdominal aortic aneurysm (AAA) repair may contribute to the development of the systemic inflammatory response syndrome and dysfunction of various organs. The aim of this study is to investigate whether an extraperitoneal approach reduces intestinal mucosal barrier and renal dysfunction in elective infrarenal AAA repair. METHODS: Twenty patients admitted for elective infrarenal AAA repair were randomized into either the transperitoneal approach (n=10) or the extraperitoneal approach (n=10). Intestinal permeability was measured preoperatively, and at day 1 and day 3 after surgery using the lactulose/mannitol test by calculating the differential urinary excretion ratio of the two sugars after oral administration. Renal dysfunction was assessed by measuring the urinary albumin/creatinine ratio (ACR) at the same time points. RESULTS: Intestinal permeability was significantly increased in the transperitoneal group at day 1 [0.124+/-0.035 (mean+/-s.e.m.)] compared to the preoperative level (0.020+/-0.003), (p=0.001) and to the extraperitoneal group at day 1 (0.025+/-0.008), (p<0.05) which showed no change in comparison with the preoperative level (0.020+/-0.003). The ACR was also significantly increased in the transperitoneal group at day 1 (16.69+/-5.12) compared to the preoperative level (5.71+/-2.89), (p<0.05) and to the extraperitoneal group at day 1 (4.33+/ 1.49), (p<0.05) which showed no significant change at any of the times examined. No correlation was observed between the lactulose/mannitol ratio and the albumin/creatinine ratio, or between age, operating time, aortic clamping time, amount of blood lost or blood transfused. CONCLUSIONS: These results support the suggestion that minimising intestinal manipulation using an extraperitoneal approach in AAA repair preserves intestinal mucosal barrier and renal glomerular functions. PMID- 11782694 TI - Naftidrofuryl in quality of life (NIQOL). A Belgian study. AB - BACKGROUND: Using a disease specific questionnaire, the Claudication Scale (CLAU S), we undertook a double blind, placebo controlled study in patients with intermittent claudication (IC) to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. METHODS: Following an initial one month placebo run-in 235 patients, with stable IC for at least 3 months, were randomized to either naftidrofuryl (Praxilene), at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and at 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients known to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared in respect to difference between the initial and final values. RESULTS: Two hundred and twenty patients (108 naftidrofuryl, 112 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions Daily living, Pain and Social life (all p<0.01). For the dimensions complaints, disease specific fears and mood, there were no significant differences between naftidrofuryl and placebo. A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p=0.047). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with IC. PMID- 11782695 TI - Occult aorto-iliac disease in patients with symptomatic coronary artery disease. AB - BACKGROUND: Atherosclerosis may affect the entire cardiovascular system despite absence of symptoms. Early changes in the wall of the carotid artery have been related to a higher morbidity and mortality from coronary artery disease (CAD). This study was conducted to investigate the relationship between the presence of occult aorto-iliac disease (OAID) and certain risk factors with the severity of CAD. METHODS: Two hundred and eighty-four consecutive patients subjected to coronary angiography (CA) were studied. Additional images of the aorto-iliac arterial segment were taken. Patients with negative CA or symptomatic lower limb arterial disease (LLAD) were excluded from further analysis. In the remaining patients, the risk factors (age, smoking, diabetes mellitus, hypertension, hyperlipidemia and positive family history for atherosclerosis) and the severity of coronary artery disease (CAD) were analyzed in relation to the presence or absence of OAID. RESULTS: Twelve patients with impaired renal function were excluded from the study. Negative CA was found in 12% (32/272) and symptomatic LLAD was present in 14% (37/272). Eligible for further analysis were 203 patients with positive CA and no LLAD. A hundred and ten of them had a positive CA and the presence of OAID whereas the remaining 93 patients had only a positive CA. The patients with OAID had more severe CAD on CA (p=0.003). There was no difference between the two groups concerning age and gender. The most common risk factors in both groups were hypercholesterolemia and a positive family history but with a significantly higher prevalence in the patients with OAID (p=0.008 and p<0.001, respectively). CONCLUSIONS: The presence of OAID in coronary patients was associated with more severe CAD and with a significantly higher prevalence of hypercholesterolemia and positive family history for atherosclerosis. This subset of patients may represent those with more aggressive atherosclerosis. PMID- 11782696 TI - A role for near infrared spectroscopy in the assessment of intermittent claudication. AB - BACKGROUND: Near infrared spectroscopy (NIRS) can be used to monitor muscle oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and cytochrome oxidase (CytOx) oxidation. We evaluated the changes in NIRS in patients with intermittent claudication (IC) pre- and postexercise. Microalbuminuria is an index of endothelial dysfunction. Therefore, we also assessed whether the urinary excretion of albumin increased postexercise in patients with IC. METHODS: Each participant (14 patients with IC and 10 controls) underwent a treadmill test; NIRS was continuously recorded. The urinary albumin:creatinine ratio (ACR) and ankle: brachial systolic pressure index (ABPI) were measured pre- and postexercise. RESULTS: The ABPI in the claudicants dropped significantly (p<0.001) postexercise. The pre-exercise ACR did not differ between claudicants and controls but postexercise, the ACR increased significantly (p<0.001) in the claudicants. There was a significant (p<0.001) difference in the degree of HbO2 deoxygenation between claudicants and controls; the rate of deoxygenation was significantly higher in claudicants than in controls (-8.4 vs. -3.4 mol/L.min, p=0.024). The period of recovery of HbO2 postexercise was also significantly slower in claudicants (192 vs 68 sec, p=0.003). There was a significant correlation between the increase in the ACR and time of recovery of HbO2 levels postexercise (r=0.86, p<0.001, n=24). A similar pattern was seen with CytOx. CONCLUSIONS: NIRS may provide a simple, non-invasive assessment of the severity of IC. Furthermore, because the ACR is a marker of endothelial damage, it is possible that NIRS changes also reflect endothelial integrity. These applications of NIRS technique should be assessed in a larger study. PMID- 11782697 TI - Raynaud's phenomenon (primary or secondary to systemic sclerosis). The usefulness of laser-Doppler flowmetry in the diagnosis. AB - BACKGROUND: Raynaud's phenomenon (RP) consists of painful vascular spasms of the extremities stressed by cold exposure. It is often a symptom, in many cases the onset, of systemic sclerosis (SSc). The aim of this study was to evaluate the role that laser-Doppler flowmetry (LDF) could have in the differential diagnosis of these disorders and to characterize the functional behaviour of the microvessels in RP. METHODS: In this study we examined 52 patients (five males and 47 females, aged 17-57) affected by primary RP, 21 patients (three males and 18 females, aged 31-63) affected by RP secondary to SSc as defined by Wouda in 1987 and 20 healthy subjects (three males and 17 females, aged 26-58) by means of LDF with an appropriate cold-test (11 degrees C for 2 min). RESULTS: We show that the cold test applied at hand level can distinguish RP patients from healthy subjects. Data show that basal blood flow of patients affected by SSc is diminished in its medium value and presents a typical tracing without vasomotion in comparison to healthy subjects and also to patients affected by primary RP. On the basis of our data among the primary RP patients we can also distinguish a group that show basal blood flow tracing very similar to that of sclerodermic patients. These subjects should be carefully followed-up. CONCLUSIONS: In conclusion, it could be stimulating for the future to introduce LDF as a complementary method for the diagnosis of RP and possibly for early discrimination between the primary disease and that secondary to SSc. PMID- 11782698 TI - Detection of myocardial involvement in systemic lupus erythematosus: mismatch between normal perfusion scans with 201Thallium and pathological 18FDG uptake. AB - BACKGROUND: Systemic lupus erythematosus (SLE) patients can frequently present cardiac symptoms, however its etiology is not well known. METHODS: EXPERIMENTAL DESIGN: prospective study. SETTINGS: specialized out-patient unit for SLE patients at an university hospital. PATIENTS: 15 SLE patients (13 females, 2 males; age range 18-64 years). INTERVENTIONS: metabolic studies of the heart were done using 18F-deoxy-glucose (18FDG, 296-333 MBq on a 2-head hybrid system) as well as heart perfusion studies (111MBq 201Tl). Additional studies: resting ECG, echocardiography, stress ECG, immunological activity parameters, antibody analyses (ANA, ENA, anti-cardiolipin antibodies), CPK, troponin-T, and lipid profiles. MEASURES: degree of correlation between conventional diagnostics and the imaging techniques. RESULTS: Abnormal ECG in 10 cases, pericardial involvement in 11 cases, elevated CPK in 1 case. ANTIBODY PROFILES: anti cardiolipin in 10/15, ENA in 9/15, ANA in 14/15. None of these changes were associated with parameters of immune activation. In the majority of cases (10/15) the 18FDG scan showed a speckled, inhomogeneous pattern of distribution, which contrasted sharply with a normal 201Tl scan. A similar pattern was observed in the patients with ocular mitochondrial myopathy, the anti-phospholipid syndrome as well as in dermatomyositis. CONCLUSIONS: Our preliminary results suggest that SLE patients with cardiac symptoms may have an abnormal glucose metabolism of the myocardium as shown by a pathological 18FDG scan, whereas perfusion appears to be normal (reversed mismatch). The lack of correlation with acute elevation of cardiac enzymes or with ECG changes suggest a chronic process. PMID- 11782699 TI - Sclerosants in microfoam. A new approach in angiology. AB - BACKGROUND: The aim of this work was to study the outcomes of echosclerosis using sclerosants in microfoam incompetent long saphenous veins, hypertensive venous ulcers and inoperable venous malformations and to record any secondary effects. METHODS: We examined the records, pre- and post-treatment and follow-up colour photographs, and echo Doppler images for: 415 patients with incompetent long saphenous veins of diameter more than 9 mm in 265 patients suffering from postsurgical recurrence of varicose saphenous veins; 72 patients with venous ulcers; and 31 with venous malformations. All patients had been treated with ultrasound-guided injections of sclerosants in microfoam. RESULTS: After 4-6 years follow-up, 80% of the long saphenous veins were obliterated and all superficial branches had disappeared in 95% of legs. In the post-surgical recurrence group, 81% of recurrent veins were obliterated and 90% of the branches had disappeared. Among the patients with ulcers, the latter remain closed after a mean of 2.5 years treatment in 77% of the cases; recurrence in the remainder was due to recanalisation of perforating veins. All venous malformations were reduced in size and 9 of them had disappeared completely. Minor transient adverse effects included coughing, inflammation and photopsia. There were no serious complications, such as deep vein thrombosis or pulmonary embolism or scotoma. CONCLUSIONS: The quality and stability of the outcomes and the low complication rate observed in this preliminary study may make sclerotherapy with microfoam the therapeutic approach of choice for the anatomical and functional elimination of an extensive range of venous pathology. Controlled trials on a standardised sclerosant microfoam are now required to confirm these results to make the method widely available. PMID- 11782700 TI - Recurrent carotid artery stenosis: natural history and predisposing factors. A long-term follow-up study. AB - BACKGROUND: The aim of this study was to evaluate the impact of various risk factors, excluding the type of closure of the arteriotomy, on the development of recurrent carotid stenosis after carotid endarterectomy. TYPE OF STUDY: single center, open prospective. METHODS: Three hundred and eight patients, who underwent a total of 338 carotid endarterectomies, were evaluated postoperatively with color duplex 1 month after the operation and every 6 months thereafter, the mean duration of follow-up being 52 months (range: 6-144). Only patients submitted to primary closure of the arteriotomy were included. Statistical analysis was performed using the Kaplan Meier method, the log rank test and Cox regression analysis. RESULTS: Three patients (0.9%) died during the perioperative period. Three (0.9%) patients had a transient ischemic attack and 7 (2.1%) a nonfatal stroke. Recurrent carotid stenosis of >50% was identified in 11 patients, leading to a 21.6% cumulative restenosis rate at 10 years of follow-up. Only one of the 11 patients with restenosis developed neurological symptoms during the follow-up period. Both univariate and multivariate analyses showed that coronary artery disease was significantly associated with restenosis, while patients with uniformly echogenic plaques as well as those with hypercholesterolemia showed a lower incidence of restenosis. CONCLUSIONS: The cumulative recurrent stenosis rate following carotid endarterectomy was 21.6% at 10 years of follow-up. Restenosis was symptomatic in 1 patient. Coronary artery disease was associated with an increased risk of restenosis, while uniformly echogenic plaques and hypercholesterolemia were associated with a lower risk. PMID- 11782702 TI - Intravenous leiomyoma with cardiac involvement. AB - We report a case of intravenous leiomyomatosis (IVL) in a 44-year-old woman, presenting with cardiothoracic clinical manifestations. Such a rare neoplastic condition most often arises from the uterine veins. At times it may reach the right cavities of the heart and it must be considered in the differential diagnosis with a cardiac myxoma or a thrombus. PMID- 11782701 TI - Clinical and hemorheological effects of buflomedil in diabetic subjects with intermittent claudication. AB - BACKGROUND: Changes in blood rheology have been described in diabetes mellitus. Buflomedil, a vasoactive substance with hemorheological properties, has been widely used in the treatment of intermittent claudication. The aim of this study was to evaluate the effect of buflomedil on clinical and hemorheological parameters in subjects with type 2 diabetes and intermittent claudication. METHODS: Forty patients were randomly assigned to oral buflomedil or matching placebo for six months in a double-blind manner. Initial and absolute walking distances were assessed by a standard treadmill testing protocol. Erythrocyte deformability was estimated with a whole blood filtration technique. ADP- and collagen-induced platelet aggregation was assessed with an aggregation profiler. beta-thromboglobulin and platelet factor-4 were measured with radioimmunoassays. All tests were performed at baseline and after three and six months of treatment. RESULTS: A significant increase in the mean initial (71%) and absolute (68%) walking distance was achieved only in the buflomedil group. ADP- and collagen induced platelet aggregation was significantly reduced in the buflomedil group, while no significant changes in erythrocyte deformability, beta-thromboglobulin and platelet factor-4 levels were noticed. However, beta-thromboglobulin levels increased significantly in the placebo group. CONCLUSIONS: These findings suggest the therapeutic efficacy of buflomedil in diabetic subjects with intermittent claudication. The inhibition of platelet aggregation and the influence on platelet activity exerted by the drug could play an important role in its clinical effect and may be of value in the treatment of such patients. PMID- 11782703 TI - Late non-anastomotic false aneurysm formation in femoropopliteal polyethylene terephthalate grafts. AB - Despite the proven reliability of polyethylene terephthlate (PET) grafts, structural defects resulting in graft rupture and false aneurysm formation have been sporadically described. Two cases of late, non anastomotic, false aneurysms of PET femoropopliteal grafts, are reported. The diagnosis is readily apparent on clinical examination and imaging studies, which display an aneurysm along the course of the graft, remote from the anastomosis. The extent of the repair depends on the extent of the degenerative process. PMID- 11782704 TI - Successful surgical repair of a ruptured abdominal aortic aneurysm in a nonagenarian. AB - Mortality due to the surgical treatment of ruptured abdominal aortic aneurysms (RAAA) is high, more than 40%, especially in elderly patients. The literature concerning RAAA in very elderly patients is analyzed by Internet research (Medline). Only rare examples of emergency surgical management in nonagenarian patients are reported, and even fewer reports of successfully operated patients. A case report of a successful surgical repair of RAAA in a nonagenarian is presented. After ultrasound (US) and CT scans, the patient (in good condition as regards blood pressure, respiratory, cardiac and renal function) underwent uneventful aneurysmectomy and reconstruction of the aorta and common iliac arteries by means of a bifurcated prosthesis. The length of hospitalization was 30 days and the patient is still alive and in good condition four years and two months after the operation. The advisability of emergency surgical repair in these patients, questionable because of the excessive surgical risk and poor survival benefit, is discussed. However many other factors affect the outcome of emergency repair (mainly cardiac, respiratory and renal function), independently of age. The authors conclude that age per se does not limit the indication for or success of surgery in very elderly patients. PMID- 11782705 TI - [Radioisotopic imaging of neuroendocrine tumours. Which radiopharmaceutical and which diagnostic procedure?]. AB - Neuroendocrine tumours can be visualized by several nuclear medicine modalities based on different mechanisms of cellular uptake. The most widely used radiopharmaceutical are the metaiodobenzylguanidine (123I/131I MIBG) and pentetreotide (111In pentetreotide). The first tracer follows the metabolic pathway of norephinephrine while the second one binds to somatostatin receptors which are expressed with high intensity on the neuroendocrine tissue. Some radiopharmaceuticals (Anti-CEA, Anti-CgA, Anti-GD2 monoclonal antibodies) have today only an experimental value, others such as 99mTc(V)DMSA had in the past very limited indications (medullary thyroid cancer) but at present their production is going to be stopped. An interesting series of new peptides showing a great affinity for the receptors/structures expressed by the neuroendocrine tissue is under evaluation in order to obtain a better tumour specificity. Among the positron-emitting radiopharmaceuticals, the 18F-fluorodeoxyglucose (FDG), in spite it is considered the most widely used tracer for clinical PET in oncology, did not show a satisfactory uptake in the well differentiated neuroendocrine tissues. On the contrary 18F-FDG is the best radiopharmaceutical to visualize those rare poorly differentiated neurondocrine tumours with a high proliferative index. For this reason also in this area, new radiopharmaceuticals have been studies and developed. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. Another radiopharmaceutical in development for PET is 11C L-DOPA which seems to be useful in visualizing endocrine pancreatic tumours. 18F-DOPA whole body PET may be a more promising imaging approach. Aim of this review is to summarize the potential of nuclear medicine techniques in the diagnosis of neuroendocrine tumours and to stresses the renewed role of nuclear medicine in the management of this disease. PMID- 11782706 TI - [State of the art and therapeutic prospects in neuroectodermal tumours and other neuroendocrine pathologies]. AB - The clinical and biological characteristics of neuroectodermal tumours (NETs) are such that their treatment is necessarily multidisciplinary. Surgery is the first therapeutic choice given that it is the only potentially curative treatment for this type of neoplasm. Medical treatment is mainly indicated in the treatment of metastatic disease and must be separated into three basic options: chemotherapy, immunotheraphy and hormone treatment. Owing to the low proliferative index generally found in NETs, chemotherapy is not very effective as a means of controlling tumour growth. Data in the literature on interferon suggest that it plays a limited role in the treatment of NETs, as do the preliminary results from studies on the association of interferon + chemotherapy. The introduction of somatostatin analogs in clinical practice represents an effective tool in the therapeutic strategy for NETs and has opened new possibilities for the management of other neoplasms. One particularly interesting aspect of the octreotide mediated antitumour action concerns the blocking of tumour neo-angiogenesis. The majority of non-endocrine tumours also express specific somatostatin receptors and in theory it is possible to hypothesise an antiproliferative action also in tumours without these receptors mediated by the indirect antiproliferative effects of somatostatin. PMID- 11782707 TI - [Somatostatin analogues for the treatment of gastro-entero-pancreatic neuroendocrine tumours]. AB - Somatostatin has represented a significant breakthrough in the treatment of patients with hormone-acting, neuroendocrine gastro-intestinal-pancreatic (NEGEP) neoplasms, even if its short half-life made it impractical in the clinical practice. Over the last recent years new long-acting formulations have been developed from the native peptide. Octreotide, lanreotide and vapeotide are octapeptides with similar biological activity, remarkable stability and longer half-life; an extended-release formulation of octreotide (Octreotide-LAR) and lanreotide (Lanreotide-SR) have been more recently developed by incorporating the peptide in microspheres of a biodegradable polymer. This formulation was conceived to provide patients with the convenience of a once-a-month or twice-a month injection and to ensure a stable serum concentration between injections and good clinical control of NEGEP tumours symptoms. Nowadays, somatostatin long acting analogues represent the first treatment option in those patients who doesn't underwent radical surgery; in addition, these substances present no important side effects, ameliorate the prognosis and can exert some degree of tumour growth control. PMID- 11782708 TI - [New therapeutic strategies in gastroenteropancreatic neuroendocrine tumours]. AB - Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the time of diagnosis when they are inoperable, accompanied by severe symptoms, sometimes of an endocrine nature. Current therapeutic procedures include surgery, embolisation of hepatic metastases, local radiotherapy, biotherapy and chemotherapy. Over the years somatostatin analogs, of which octreotide is the first form, have become increasingly important in the treatment of patients with neuroendocrine tumours. A major step forward in analog treatment is represented by the development of slow-release formulas which do not require multiple daily injections and reduce the onset of resistance. The treatment of neuroendocrine tumours in the future will be based on the increased use of somatostatin analogs alone or in association with interferon or chemotherapy, and will also include surgery, radiometabolic therapy and targeted irradiation of the tumour. PMID- 11782709 TI - [New therapeutic prospects in microcytoma]. AB - The therapeutic efforts of the past thirty years have been directed at improving the scant prognosis of patients suffering from microcytoma (SCLC) using a combination of chemotherapy and radiotherapy. Studies have shown that the longest survival rates are achieved when radiotherapy is administered concomitantly with chemotherapy. No clear correlation has been identified between the 3-year disease free survival rate and the type of chemotherapy used. The standard treatment for patients suffering from SCLC is currently polychemotherapy using protocols with cisplatin, with or without radiotherapy. Among the new protocols that have been proposed, an increase in dose intensity, weekly therapy and alternating chemotherapy appear to give the most promising results, even if no studies have so far actually demonstrated their ability to improve results. PMID- 11782710 TI - [The role of surgery in the treatment of small cell lung cancer]. AB - Small cell lung cancer (SCLC) is a biologically aggressive tumor with a low long term survival rate. SCLC is highly responsive to chemotherapy and surgery has a very limited role in its treatment because the disease is usually widely disseminated at the diagnosis. Good results from surgery have been reported in the small subgroup of T1-2 N0 M0 patients. In N1 peripheral SCLC, surgery in combination with other treatments, can obtain fair results. Surgical treatment does not influence the prognosis in SCLC as stage III and IV. PMID- 11782711 TI - [Current role of radiotherapy in the treatment of SCLC]. AB - Microcytoma (SCLC) is generally regarded as a disease requiring chemotherapy and is only treated with radiotherapy using combined protocols. A number of different approaches have been proposed, changing timing, dose and fractionation. A different role is played by irradiation of the brain in the treatment of metastases. The authors discuss the role of radiotherapy in the treatment of SCLC and in study protocols through an analysis of a personal series. PMID- 11782712 TI - [New therapeutic strategies in microcytoma]. PMID- 11782713 TI - [Role of the surgeon in the treatment of small cell lung carcinoma]. AB - Surgery has never played a precise and well consolidated role in the planned treatment of lung microcytoma (SCLC). The acknowledged therapeutic strategy associates local treatment (radiotherapy) with general treatment (chemotherapy). Exeresis is particularly indicated in limited or peripheral forms, followed by intensive polychemotherapy. Scintigraphy with octreotide may be used for the initial screening of patients with widespread disease. Another minor role played by surgery is in the treatment of neoplastic foci remaining after chemotherapy. In some cases the use of a radioguided method which, after intravenous injection of radiolabeled octreotide, allows the accumulation of somatostatin analog in neoplastic foci to be assayed intraoperatively using a manual probe, might help the surgeon to check the radical nature of the operation. In addition, octreotide can be used as a radiotherapeutic pharmacological agent or to enhance the efficacy of chemotherapy in microcytoma and other lung tumours with neuroendocrine differentiation. PMID- 11782714 TI - [CT in findings intestinal carcinoids]. AB - CT findings in intestinal carcinoids are various. While recognition of the primary tumour is a rare event, the contribution of CT in evaluating patients with suspected intestinal carcinoid is relevant, both for loco-regional staging and during long-term follow-up. Moreover, in the relatively frequent cases with an aspecific clinical onset, CT may be findings useful to direct diagnosis. PMID- 11782715 TI - [Somatostatinergic control of Kaposi's sarcoma growth through the inhibition of angiogenesis]. AB - Somatostatin and its analogs are active in the inhibition of the proliteration of sst receptor positive endocrine neoplasms, however their activity and mechanism in non-endocrine tumors is not clear. Somatostatin effectively inhibited the growth of a Kaposi's sarcoma xenograft in nude mice, yet in vitro the tumor cells did not express any known somatostatin receptors and were not growth inhibited by somatostatin. Histological examination revealed limited vascularization in the somatostatin treated tumors as compared to the controls. Somatostatin was a potent inhibitor of angiogenesis in an in vivo assay. In vitro, somatostatin inhibited endothelial cell growth and invasion. Migration of monocytes, important mediators of the angiogenic cascade, was also inhibited by somatostatin. Both cells types expressed somatostatin receptor mRNAs. These data demonstrate that somatostatin is a potent anti-tumor angiogenesis compound directly affecting both endothelial and monocytic cells. The debated function of somatostatin in tumor treatment and the design of therapeutic protocols should be reexamined considering these data. PMID- 11782716 TI - [The activation of the phosphotyrosine phosphatase eta is responsible for the somatostatin inhibition of PCCl3 thyroid cell proliferation]. AB - BACKGROUND: This study was aimed to identify possible intracellular effectors of the somatostatin (SST) antiproliferative activity, in PCCl3 thyroid cells. METHODS: To prove the involvement of r-PTPeta in SST's effect, we studied th proliferative activity of subclones of PCCl3 cells that do or do not express this PTP. RESULTS: SST inhibited PCCl3 TSH+insulin-dependent cell proliferation through the induction of a phosphotyrosine phosphatase (PTP) activity, detected using the synthetic substrate pNPP (+150%, p<0.01). Conversely, PCCl3 cells stably expressing the v-mos oncogene (PCmos) were completely insensitive to SST antiproliferative effects due to the incapability of SST to increase PTP activity, that correlated with the abolishment of the expression of the receptor like PTP, r-PTPeta. In the cells in which r-PTPeta was transfected (PCmos/ PTPeta) SST inhibited cell proliferation showing a dose-dependence similar to that observed in PCCl3 cells. Conversely, the transfection of a catalytically inactive mutant of r-PTPeta did not restore the responsivity to SST. Also in PCmos/PTPeta cells SST, treatment increased membrane PTP activity. CONCLUSIONS: SST inhibition of PCC13 cell proliferation requires the activation of r-PTPeta. PMID- 11782717 TI - [Role of radio-guided surgery with 111In-octreotide in the treatment of thoracic neoplasms]. AB - The study evaluates the role of radio-guided surgery (RGS) with 111In-octreotide in the treatment of lung neoplasms. RGS with octreotide appears to be useful in surgery, above all during the intraoperative staging of the tumour; it can define with greater precision the extent of the resections extended towards the lung wall and ensure a radical approach in minimal lung resections. PMID- 11782718 TI - [Comparison between integrated 24-hour concentrations of growth hormone, insulin like growth factor I and prolactin in acromegalic patients treated with octreotide and patients treated with octreotide LAR]. AB - The current therapeutic options for acromegalic patients (surgery, radiation therapy and/or pharmacological treatment) do not always lead to a definitive resolution of the disorder. Recently, octreotide (OC) and, more recently, octreotide LAR (OC-LAR), a new slow-release formulation of the long-acting somatostatin analog, have been regarded as the primary treatment for acromegaly. This study reports our observations of the integrated 24-hour concentrations of GH, IGF-I and prolactin (PRL) in acromegalic patients treated with octreotide (OC) and octreotide LAR (OC-LAR), highlighting lower percentages of apparent remissions. PMID- 11782720 TI - [Carotid glomus tumours. Personal experience in the surgical treatment of chemodectoma]. AB - The authors present 6 cases of carotid glomus tumours referred to their attention over the past 10 years. Their experience shows that colour ultrasonography (using both morphological and functional evaluation) is the diagnostic key for defining the treatment of paraganglioma. More recent experience highlights the role of 111In Pentreotride using a multidisciplinary therapeutic approach. PMID- 11782719 TI - [Efficacy of somatostatin analogs in the treatment of neuroendocrine tumours and paraneoplastic syndromes]. AB - BACKGROUND: The authors report their experience with octreotide LAR in the adjuvant treatment of 10 patients suffering from neuroendocrine tumours and paraneoplastic syndromes. METHODS: All patients were studied preoperatively using traditional radiology and scintigraphy using octreoscan. RESULTS: Octreoscan was positive in all cases for somatostatin receptors. All patients with neuroendocrine tumours underwent surgery of the primary neoplasm; treatment with somatostatin was commenced at a later stage. CONCLUSIONS: The authors' experience with octreotide LAR proved to be an efficacious means of controlling symptoms and stabilising disease without collateral effects. They conclude by affirming that octreotide LAR represents a valid therapeutic choice in the symptomatic treatment of neuroendocrine tumours. PMID- 11782723 TI - In search of miracles: a physician volunteer at Ground Zero. PMID- 11782724 TI - World Trade Center perspective from a Manhattan emergency medicine resident. PMID- 11782725 TI - The bar at Ground Zero. PMID- 11782726 TI - A randomized, controlled trial of clinical information shared from another institution. AB - STUDY OBJECTIVE: Emergency physicians often must deliver medical care with minimal access to historical clinical information. We demonstrate the feasibility and potential value of increased access to patients' clinical information from another hospital while they are receiving care in the emergency department. METHODS: We conducted a pilot randomized, controlled trial of providing information from a large, longitudinal, computer-based patient record system of clinical data from an urban hospital to emergency physicians at either of 2 urban EDs. We randomized patients seen at either ED to have the information from the computer-based patient record system provided to their physician or to not have the information provided. We delivered information to the emergency physician both as a printed abstract and by means of online access to the computer-based patient record. We assessed charges, hospital admissions, repeat visits to EDs, and the emergency physicians' satisfaction with the information. RESULTS: Under certain assumptions, the intervention was estimated to decrease charges for ED care by approximately $26 per encounter (P =.03) at 1 hospital, but there was no effect on charges at the other hospital. This result was likely because of marked differences in the workflows and information access at these 2 EDs. We demonstrated no differences in admission rates or repeat visits to the ED. Emergency physicians identified that remembering their passwords and the time required to search for the information were significant barriers to accessing clinical information online. CONCLUSION: Our pilot study is the first to demonstrate the feasibility of sharing clinical information between different health care systems. We observed a trend toward cost savings at 1 of 2 hospitals and no differences in the quality measures we studied. Our experience underscores the difficulties inherent in studying the effects of community-wide health care interventions on cost and quality of ED care. PMID- 11782727 TI - Managed care gatekeeping, emergency medicine coding, and insurance reimbursement outcomes for 980 emergency department visits from four states nationwide. AB - STUDY OBJECTIVE: We analyzed 980 emergency department visits for 951 patients with managed care insurance to document gatekeeping interactions and compare ED coding with professional fee billing reimbursements. METHODS: A prospective cohort study was performed at 12 academic and community hospital EDs in 4 states involving consecutive ED patients with managed care insurance. The main outcomes measured were gatekeeper decisions, coding levels, and reimbursement. RESULTS: Preauthorization for payment was required from managed care gatekeepers for 876 (89%) patients. Authorization was granted for 490 (56%) of these visits and denied in 176 (20%) visits; gatekeepers were not available for 210 (24%) visits. Reimbursement was initially denied for 211 (43%) of the ED visits preapproved by managed care gatekeepers. Reimbursement was initially denied for most (634 or 65%) visits, and downcoding occurred in the other 346 (35%) visits. Appeals for 560 (57%) visits resulted in a decrease in the number of unreimbursed ED visits to 193 and an increase in the number of reimbursed ED visits to 787. CONCLUSION: Preauthorization gatekeeping is not predictive of whether managed care third party payers will initially reimburse ED visits. Overall, almost two thirds of all ED claims were initially denied, and reimbursed claims were uniformly downcoded. On appeal, reimbursement was often reinstated or increased, although billing services only appealed about half of ED visits. PMID- 11782728 TI - Health status and intimate partner violence: a cross-sectional study. AB - STUDY OBJECTIVE: We identify health variables associated with a history of intimate partner violence (IPV) using self-reported and laboratory measures. METHODS: This study used a cross-sectional design. Participants were a randomized sample of English-speaking women between the ages of 18 and 50 years who presented to a large urban emergency department. Potential participants were screened in the ED for a history of physical abuse and coded as having experienced no IPV (No IPV), as having a recent history of IPV (occurring in the previous 12 months; IPVA), or as having a remote history (most recent occurrence >12 months ago; IPVHx). Participants were interviewed several days later in an outpatient setting regarding demographics, medical care use, and physical and mental health variables. Participants also received urine and blood tests and a pelvic examination. RESULTS: Self-reported health was poorest among women reporting IPVA and best among women reporting no IPVA. Women in the IPVA group differed from women with no IPV history with respect to cocaine use (odds ratio [OR] 4.8; 95% confidence interval [CI] 1.4 to 17.3), sexually transmitted diseases (OR 5.1; 95% CI 1.5 to 20.3), and nightmare frequency (OR 11.6; 95% CI 2.3 to 83.4). Women reporting IPVHx were more likely to report a history of sexually transmitted diseases than women with no IPV history (OR 4.1; 95% CI 1.6 to 11.4) and had more frequent nightmares (OR 5.0; 95% CI 1.3 to 24.9). Urine and blood tests identified only 2 variables (hemoglobin levels, mean corpuscular volume) that differed significantly between groups by IPV history; these differences were not clinically significant. CONCLUSION: Women with a recent history of IPV reported a poorer health status than women with no IPV history; laboratory testing detected few differences. PMID- 11782729 TI - The prosecution of sexual assault cases: correlation with forensic evidence. AB - STUDY OBJECTIVE: We sought to determine the association between historical and physical evidence with judicial outcome in sexual assault cases. METHODS: A population-based, retrospective review of forensic evidence was conducted for all sexual assault cases reported in Duval County, FL, during a 2-year period. Variables examined included age, race of victim, evidence of trauma (body, genital, or both), presence of spermatozoa at the time of the forensic examination, weapon use, and whether the victim knew the assailant. In cases in which an arrest was made, logistic regression was used to estimate the strength of association with the outcome of conviction in sexual assault cases. RESULTS: During the study period, 821 sexual assaults were reported, and 801 forensic examinations were performed. The victims were predominantly female (776; 97%), with 409 (51%) being black, 376 (47%) white, and 16 (2%) other minorities. A suspect was identified in 355 (44%) of the 801 cases for which a sexual assault forensic examination was conducted. No suspect was identified in 446 (56%) of these cases. There were 271 arrests made. The police did not have enough evidence to arrest a suspect after detention in 84 cases. For those cases in which a suspect was arrested, 153 had charges dropped, 89 were found guilty, 2 were found not guilty, and 27 cases were still pending or the files were sealed and unavailable for review. There was evidence of trauma in 202 (57%) of the examinations, and spermatozoa were found at the time of the forensic examination in 110 (31%) of the cases in which a suspect was identified. Logistic regression found that victims aged younger than 18 years, the presence of trauma, and the use of a weapon by the assailant were significantly associated with successful prosecution. There was a trend toward conviction if the victim was white. CONCLUSION: Emergency physicians have an obligation to provide care for victims of sexual assault cases. This care includes a possible legal defense. To that end, emergency physicians should be vigilant in the documentation of the history of the event (eg, weapon use) and in the documentation of traumatic injuries because these factors can assist in a successful prosecution. PMID- 11782730 TI - The effect of an education program on violence in the emergency department. AB - STUDY OBJECTIVE: We examine whether a specific educational effort reduces emergency department violence in the short term and quantify the amount of violence in the ED. METHODS: Cross-sectional prospective surveys were conducted at a tertiary referral center at baseline (1998) and at 3 and 6 months (1999) after the Prevention and Management of Aggressive Behavior Program (PMABP). ED staff on all shifts for 7 alternate days in a 2-week period were surveyed. We measured the total and mean number of physical and violent events per survey. A generalized estimating equation Poisson regression model examined the effect of the program on the numbers of physically and verbally violent events per shift per employee, after adjusting for other covariates. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Physical violence events per survey at baseline, 3 months posttraining, and 6 months posttraining were 0.27, 0.10, and 0.21, respectively. The number of reported violent interactions at the same intervals were 49, 19, and 46 (adjusted OR 1.0, 0.35 [95% CI 0.15 to 0.84], and 0.79 [95% CI 0.48 to 1.40]), respectively. Verbal violence events per survey at baseline, 3 months posttraining, and 6 months posttraining were 0.85, 0.31, and 0.51, respectively. The number of reported interactions involving verbal violence at the same intervals were 154, 58, and 69 (adjusted OR 1.0, 0.31 [95% CI 0.21 to 0.46], and 0.47 [95% CI 0.33 to 0.66]), respectively. CONCLUSION: Violent events are frequent in the ED. Education programs may reduce the number of events at least temporarily but do not clearly reduce violence in the long term. PMID- 11782731 TI - Violence-inflicted injuries: reporting laws in the fifty states. AB - STUDY OBJECTIVE: Physicians have an important role in the diagnosis, treatment, and documentation of violence-inflicted injuries. Physicians may also be legally mandated to report these assault-related injuries to law enforcement. Previous studies have shown that physicians may not be aware of the reporting laws in their state. The objective of this study was to review the reporting laws for violence-inflicted injuries in adults in the 50 states and the District of Columbia, with particular emphasis on domestic violence. METHODS: Members of a domestic violence research interest group contacted individual state legislatures regarding mandated reporting by health providers of violence-inflicted injuries in adults. This information was then verified by each state's domestic violence coalition. Statutes regarding child abuse or sexual assault and statutes concerning injuries in incapacitated adults were not included in this study. RESULTS: Five states (Alabama, New Mexico, South Carolina, Washington, and Wyoming) have no specific reporting requirements for health providers treating patients with assault-related injuries. Forty-two states have reporting requirements for injuries resulting from firearms, knives, or other weapons. Twenty-three states have reporting requirements for injuries resulting from crimes. Seven states have statutes that specifically require health providers to report injuries resulting from domestic violence. CONCLUSION: Forty-five states have laws that mandate physician reports of injuries caused by weapons, crimes, or domestic violence. Physicians need to be aware of the existence of these laws and of their state's specific requirements. PMID- 11782732 TI - Do all emergency physicians have an obligation to provide care for victims of sexual assault or is there a more effective alternative? PMID- 11782733 TI - Amusement park injuries and deaths. AB - Media coverage of amusement park injuries has increased over the past several years, raising concern that amusement rides may be dangerous. Amusement park fatalities and increases in reported injuries have prompted proposed legislation to regulate the industry. Since 1979, the medical literature has published reports of 4 subdural hematomas, 4 internal carotid artery dissections, 2 vertebral artery dissections, 2 subarachnoid hemorrhages, 1 intraparenchymal hemorrhage, and 1 carotid artery thrombosis with stroke, all related to roller coaster rides. In this article, we review reports of amusement park injuries in the medical literature and Consumer Product Safety Commission data on the overall risk of injury. We also discuss the physics and the physiologic effects of roller coasters that may influence the type and severity of injuries. Although the risk of injury is low, emergency physicians are advised to include participation on thrill rides as part of their history, particularly when evaluating patients presenting with neurologic symptoms. PMID- 11782734 TI - Type IV renal tubular acidosis presenting as dyspnea in two older patients taking angiotensin-converting enzyme inhibitors. AB - The evaluation of dyspnea most often leads to a cardiac or pulmonary diagnosis. In the elderly, however, the cause is commonly multifactorial. The emergency physician should always consider noncardiopulmonary etiologies when treating such patients. We present 2 cases of new-onset type IV renal tubular acidosis (RTA) in older patients taking lisinopril who presented to the emergency department as dyspnea. Both patients had chronic cardiopulmonary illnesses and were initially diagnosed as having either congestive heart failure, asthma exacerbations, or both. The laboratory results for RTA are specific and the diagnosis can be made in the ED. PMID- 11782735 TI - Evidence-based medicine. A primer for the emergency medicine resident. PMID- 11782736 TI - Cellular telephone use survey. PMID- 11782737 TI - Malaria deaths following inappropriate malaria chemoprophylaxis--United States, 2001. PMID- 11782738 TI - Lungs is just for breathin'. PMID- 11782739 TI - The conservation of matter. PMID- 11782740 TI - Bolus ejection: a method for removing sea urchin spines. PMID- 11782741 TI - Beyond left bundle-branch block: looking for the acute transmural myocardial infarction. PMID- 11782742 TI - Beyond left bundle-branch block: looking for the acute transmural myocardial infarction. PMID- 11782743 TI - Electrocardiographic diagnosis of acute myocardial infarction in the presence of left bundle-branch block: can we "treat all" patients? PMID- 11782745 TI - In defense of patient privacy. PMID- 11782746 TI - Clinical policy: critical issues in the evaluation and management of patients presenting to the emergency department with acute headache. AB - This clinical policy focuses on critical issues in the evaluation and management of patients with acute headache. A MEDLINE search was performed, abstracts were reviewed, and appropriate full-text articles were read; references from reviewed articles were searched for additional material. This policy focuses on 4 areas of current interest and/or controversy in acute headache management: (1) response to headache therapy as an indicator of underlying pathology, (2) clinical findings predictive of increased intracranial pressure, (3) indications for emergent neuroimaging in patients with a complaint of headache, and (4) indications to pursue emergent diagnostic studies in patients with thunderclap headache but with normal findings on a head computed tomography (CT) scan and negative findings on a lumbar puncture. Recommendations for patient management are provided for each of these 4 topics based on strength of evidence. Level A recommendations represent patient management principles that reflect a high degree of clinical certainty, Level B recommendations represent patient management principles that reflect moderate clinical certainty, and Level C recommendations represent other patient management strategies based on preliminary, inconclusive, or conflicting evidence, or based on panel consensus. This guideline is intended for physicians working in hospital-based emergency departments. PMID- 11782747 TI - Christiaan Neethling Barnard (1922-2001). PMID- 11782748 TI - Innovative techniques to enhance lung preservation. PMID- 11782749 TI - Congenital heart disease outcome analysis: methodology and rationale. PMID- 11782750 TI - Comparing apples and oranges. PMID- 11782751 TI - Unrealistic expectations arising from mortality data reported in the cardiothoracic journals. AB - BACKGROUND: This study was undertaken to ascertain whether mortality data in the cardiac surgical literature mirror data reported in national databases. METHODS: This was a review of articles with 50 or more subjects reporting single-center mortality data for coronary artery bypass or aortic or mitral valve replacement published in the three major cardiothoracic surgical journals from 1997 through 2000. Mortality data and trends were examined. RESULTS: One hundred sixty-nine articles were found (coronary artery bypass, n = 119; aortic valve replacement, n = 34; mitral valve replacement, n = 16). Articles were predominantly case series (N = 95), with smaller numbers of comparative retrospective studies (n = 34), randomized trials (n = 29), and prospective noncomparative studies (n = 11). The median mortality figures for these studies were 1.5% (interquartile range, 0.3% 2.6%) for coronary artery bypass, 3.4% (interquartile range, 2.0%-5.3%) for aortic valve replacement, and 4.7% (interquartile range, 2.1%-6.9%) for mitral valve replacement. In contrast, the national registry mortality figures were 2.9%, 4.0%, and 6.0%, respectively, in the United States and 2.6%, 4.5% and 6.3%, respectively, in the United Kingdom. Coronary bypass studies with samples smaller than 100 patients reported lower mortality figures (median 0%) than did those with more than 100 patients (1.8%). Exploration with graphical plots suggested a bias toward reporting and publication of studies with below average mortality. CONCLUSIONS: Particularly for coronary artery bypass, published data tend to underrepresent the risk of death as seen in most centers. Outcomes and magnitudes of effects as reported in these research studies may not be replicable to the same degree in most centers. In particular, extreme caution should be taken in extrapolating results from studies with fewer than 100 patients to larger surgical populations. PMID- 11782752 TI - Prospective randomized comparison of CarboMedics and St Jude Medical bileaflet mechanical heart valve prostheses: an interim report. AB - OBJECTIVE: This is a midterm report of a study comparing the clinical performance of CarboMedics and St Jude Medical heart valve prostheses through a projected 10 year period. METHODS: Between 1992 and 1996, a total of 485 patients undergoing mechanical valve replacement were prospectively randomly assigned to receive either CarboMedics (n = 234) or St Jude Medical (n = 251) prostheses for aortic (n = 288), mitral (n = 160), or double (n = 37) valve replacements and were followed up annually. RESULTS: Baseline and operative characteristics were similar between the two groups with respect to major demographic characteristics, preoperative clinical status, and operative data. Mean follow-up was 50 +/- 22 months for the CarboMedics group (97% complete) and 47 +/- 20 months for the St Jude Medical group (96% complete), yielding a total of 1959 patient-years. The 30 day mortality, and 5-year actuarial survival, and linearized survival were 6.0%, 82.4% +/- 2.6%, and 4.3% per patient-year in the CarboMedics group and 4.4%, 79.9% +/- 2.8%, and 4.7% per patient-year in the St Jude Medical group (log-rank P =.7). Freedom at 5 years from valve-related mortality, major thromboembolism, hemorrhage, and other nonstructural valve dysfunction was, respectively, 96.7% +/ 1.4% (0.7% per patient-year), 90.9% +/- 2.1% (2.2% per patient-year), 87.3% +/- 2.5% (3.6% per patient-year), and 96.1% +/- 1.4% (0.7% per patient-year) in the CarboMedics group and 95.9% +/- 1.5% (1.0% per patient-year), 92.5% +/- 1.8% (2.0% per patient-year), 82.6% +/- 2.8% (4.3% per patient-year), and 96.0% +/- 1.3% (0.6% per patient-year) in the St Jude Medical group, with no overall intergroup differences. No statistically significant intergroup differences in international normalized ratio values were detected during the study period. CONCLUSIONS: This study shows no significant differences in the early and midterm clinical outcomes between patients who received CarboMedics valve prostheses and those who received St Jude Medical mechanical prostheses. Choices with respect to valve type can be based on considerations other than patient outcome. PMID- 11782753 TI - One-year appraisal of a new aortic root conduit with sinuses of Valsalva. AB - OBJECTIVES: We evaluate the clinical results 1 year after an anatomic reconstruction of the aortic root in which we used a specifically designed aortic root prosthesis that incorporates the sinuses of Valsalva. MATERIAL AND METHODS: The new aortic Dacron prosthesis has a proximal portion in the Dacron conduit that expands on implantation, creating pseudosinuses. During a 12-month period, 28 patients (mean age 59 +/- 14 years) underwent a Bentall operation (12 cases), a remodeling procedure (7 cases), and a reimplantation procedure (9 cases) with the use of a new aortic root conduit. All patients had aortic root aneurysm with an anatomically normal (for the valve-sparing procedure) or diseased aortic valve (for the Bentall operation). Five patients had aortic dissection and 5 had Marfan disease. The mean follow-up was 6 +/- 3 months. All patients underwent postoperative transesophageal and transthoracic echocardiographic studies. RESULTS: All patients survived and were in good clinical condition at the latest follow-up. Postoperative echocardiography showed a marked reduction in ventricular volumes in all patient groups (P <.0005). In the Bentall group the new prosthesis appeared to reduce the tension on the coronary ostial sutures. In patients undergoing both types of valve-sparing procedures a similar normal anatomy of the aortic root was reconstructed. In the reimplantation group the anulus was smaller than in the remodeling group (P =.01). Patients undergoing the reimplantation procedure had less bleeding and a lower incidence of residual valve insufficiency. CONCLUSIONS: The new aortic root prosthesis allowed the reconstruction of the aortic root anatomy in all types of surgical techniques with low postoperative morbidity. PMID- 11782754 TI - Methicillin-resistant Staphylococcus aureus infection in a cardiac surgical unit. AB - BACKGROUND: Increased antibiotic resistance of common bacteria is attributed in part to the widespread use of various antibiotic agents. Prophylactic and therapeutic antibiotic treatments are routinely used in cardiac surgical units, and it is no surprise that methicillin-resistant Staphylococcus aureus infection is becoming a major cause of surgical infections in cardiac patients. METHODS: We reviewed our experience with patients who underwent cardiac surgery and experienced infection caused by methicillin-resistant Staphylococcus aureus. Between 1992 and 2000 at the Montreal Heart Institute, 39 patients had methicillin-resistant Staphylococcus aureus surgical infections, and 13,199 patients underwent cardiac surgery. The yearly incidence of methicillin-resistant Staphylococcus aureus infection, the relative risk of acute mediastinitis and of superficial wound infections or other types of methicillin-resistant Staphylococcus aureus infection episodes, and the effect of preventive measures were analyzed. RESULTS: The annual incidence of methicillin-resistant Staphylococcus aureus acute mediastinitis decreased from 0.37% (5/1321) of cardiac patients in 1992 and 0.44% (6/1355) in 1993 to 0% between 1994 and 1997, 0.13% (2/1528) in 1999, and 0% (0/1700) in 2000. The total incidence of methicillin-resistant Staphylococcus aureus infection, including mediastinitis, superficial and deep sternal and leg wound infection, and all systemic infection episodes ranged from 0.68% of patients in 1992 and 0.96% of patients in 1993 to 0.46% of patients in 1999 and 0.53% of patients in 2000. The relative risk of severe mediastinal methicillin-resistant Staphylococcus aureus infection to all other methicillin-resistant Staphylococcus aureus infection episodes decreased from 1.65 in 1992 to 0.41 in 1999 and 0 in 2000. Beginning in 1993, all patients given a diagnosis methicillin-resistant Staphylococcus aureus infection and all nasal carriers of methicillin-resistant Staphylococcus aureus were strictly isolated on the surgical unit, and vancomycin was used as the prophylactic antibiotic agent for cardiac surgery in these patients. Moreover, since 1998, all patients admitted in the hospital were screened, and nasal carriers were isolated and treated with topical antibiotic ointment. CONCLUSION: Mediastinal and other infections caused by methicillin-resistant Staphylococcus aureus have a significant morbidity in cardiac surgical patients. After an outbreak of methicillin-resistant Staphylococcus aureus mediastinal infections, several preventive measures to control methicillin-resistant Staphylococcus aureus contamination of surgical patients were implemented (nasal screening, preventive isolation, application of mupirocin, prophylaxis with vancomycin and alcohol gels) and were effective in decreasing the incidence of methicillin-resistant Staphylococcus aureus infection and mediastinitis after cardiac surgery. PMID- 11782755 TI - Effect of target stenosis and location on radial artery graft patency. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of target vessel characteristics on radial artery patency when used as a composite T graft. METHODS: Between October 1993 and March 2001, 1022 patients underwent coronary bypass with the internal thoracic artery-radial artery composite T graft. Of these, angiography has been performed on 109 patients at a mean 27.1 months (range, 2-70 months) postoperatively for symptoms of ischemia. By means of Cox proportional hazard models, the relationships between anastomotic patency and target vessel location, proximal stenosis, target diameter, and quality were assessed. RESULTS: A total of 231 radial artery anastomoses were evaluated. The mean stenosis for patent anastomoses was 82% compared with 71% for occluded anastomoses (P <.001). Anastomotic patency for targets with moderate stenosis (< or = 70%) was worse than that for vessels with critical stenosis (> or = 90%; relative risk, 1.7; 95% confidence interval, 1.3-2.2; P <.001). Patency for targets of the right coronary artery was statistically inferior to that for targets of the left anterior descending artery (relative risk, 1.8; 95% confidence interval, 1.2-2.9; P =.01) and bordered on significance versus that for the circumflex artery distribution (relative risk, 1.6; 95% confidence interval, 1.0-2.8; P =.06). When directed toward critically stenosed targets of the left anterior descending or circumflex arteries, radial artery patency was not statistically different that that of the internal thoracic artery (P =.19). CONCLUSION: Radial artery patency is sensitive to both target location and proximal target stenosis. Selective use of the radial artery to targets of the left anterior descending and circumflex distributions remains encouraging. Radial artery grafts to targets of the right coronary artery or those with moderate stenosis appear to be at particularly high risk of failure. PMID- 11782756 TI - Preserved myocardial blood flow and oxygen supply-demand balance with active coronary perfusion during simulated off-pump coronary artery bypass grafting. AB - BACKGROUND: During off-pump coronary artery bypass surgery, concern remains about the possible myocardial injury associated with the transient occlusion and stabilization of the target vessels. Although intraluminal shunts are used to avoid ischemia during graft anastomosis, blood flow through the shunts can be affected by upstream pressure and inherent resistance, resulting in reduced blood flow during hypotension or severe proximal stenosis. METHODS: In anesthetized dogs regional myocardial blood flow (microspheres), oxygen consumption, lactate extraction, and systolic shortening (sonomicrometry) were measured in the myocardium served by the left anterior descending coronary artery with native perfusion after interposition of a 2.25-mm shunt (> or = 90% of left anterior descending diameter) and during active coronary perfusion with a constant flow pump. Measurements were made under normotension and hypotension produced by partial caval occlusion to reduce arterial pressure by 50%. RESULTS: Interposition of the shunt reduced blood flow by 67.8%, regional oxygen delivery by 59.8%, and systolic shortening by 45.6% relative to baseline, but lactate extraction (31.0% vs 31.2%) and oxygen supply-consumption (O(2)S/myocardial oxygen consumption ratio, 2.7 +/- 0.5 vs 2.6 +/- 0.5) were comparable with baseline values. Hypotension further decreased these physiologic values and was associated with local lactate production (-67.4% extraction) and decreased O(2)S/myocardial oxygen consumption ratio (1.3 +/- 0.1). Active coronary perfusion was associated with regional blood flow, oxygen delivery, systolic shortening, and lactate extraction comparable with baseline values. In contrast to the shunt, active perfusion maintained myocardial flow, oxygen delivery, and lactate extraction during hypotension and normalized the O(2)S/myocardial oxygen consumption ratio, although systolic shortening decreased as a result of ventricular unloading. CONCLUSION: Intraluminal shunts may impede oxygen delivery to the target myocardium, which precipitates regional ischemia during transient hypotension. Active coronary perfusion provides adequate oxygen supply independent of systemic blood pressure. PMID- 11782757 TI - Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass. AB - OBJECTIVE: To determine whether myocardial protection is improved by restoring physiologic variability to the cardioplegia pressure signal during cardiopulmonary bypass, we compared cardiac function in pigs in the first hour after either conventional cold-blood cardioplegia (group CC) or computer controlled biologically variable pulsatile cardioplegia (group BVC). METHODS: Invasive monitors and sonomicrometry crystals were placed, and cardiopulmonary bypass was initiated. The aorta was crossclamped, and cold blood cardioplegic solution was infused intermittently through the aortic root with either conventional cardioplegia (n = 8) or biologically variable pulsatile cardioplegia (n = 8; mean pressure, 75 mm Hg for 85 minutes). The crossclamp was released, cardiac function was restored, and separation from cardiopulmonary bypass was completed. With stable temperature and arterial blood gases, hemodynamics and systolic and diastolic indices were compared at 15, 30, and 60 minutes after cardiopulmonary bypass. RESULTS: Diastolic stiffness doubled from 0.027 +/- 0.016 mm Hg/mm (mean +/- SD) at baseline to 0.055 +/- 0.036 mm Hg/mm (P =.003) at 1 hour after bypass in group CC, associated with increased left ventricular end diastolic pressure from 9 +/- 2 to 11 +/- 2 mm Hg (P =.001), mean pulmonary artery pressure from 14 +/- 2 to 20 +/- 3 mm Hg (P =.003), and serum lactate levels from 2.0 +/- 0.5 to 5.6 +/- 2.3 mmol/L (P =.008). Systolic function was not affected. In group BVC diastolic stiffness, left ventricular end-diastolic pressure, and pulmonary artery pressure values were not different from control values at any time after bypass, and serum lactate levels were significantly less than with conventional cold blood cardioplegia. Peak pressure variability with biologically variable pulsatile cardioplegia fit a power-law equation (exponent = -3.0; R(2) = 0.97), indicating fractal behavior. CONCLUSION: Diastolic cardiac function is better preserved after cardiopulmonary bypass with biologically variable pulsatile cardioplegia and fractal perfusion. This may be attributed to enhanced microcirculatory perfusion with improved myocardial protection. A model supporting these results is presented. PMID- 11782758 TI - Determinants of maximal right ventricular function: role of septal shift. AB - BACKGROUND: Right heart failure can occur after orthotopic heart transplantation and can complicate implantation of left ventricular assist devices. The functional codeterminants of right ventricular function are not fully understood. We investigated the effects of left ventricular preload and afterload, systemic pressure, and the contribution of the interventricular septum to right ventricular function. METHODS AND RESULTS: In vivo studies were conducted in 12 dogs by using a highly defined, isovolumic right heart preparation. At any given arterial pressure, maximal right ventricular developed pressure was not influenced by left heart output; however, right ventricular volumes at which peak right ventricular developed pressure occurred differed significantly between the volume-loaded versus the unloaded left ventricle (P <.05). A correlation was found between peak right ventricular developed pressure and mean arterial pressure. The shift of the interventricular septum toward the left ventricle is delayed under the influence of left ventricular volume load, but the maximal interventricular septal deformation does not differ at maximal right ventricular developed pressure. There was a substantial and significant decrease in peak right ventricular developed pressure when the interventricular septum was inactivated (P <.05). CONCLUSIONS: Right ventricular function has multiple determinants, including the right ventricular free wall, the left ventricle, and the interventricular septum. Changes in right ventricular performance caused by alterations in left ventricular volume load and mean arterial pressure are mediated partially through the interventricular septum, as well as through perfusion of the right ventricular free wall; inactivation of the interventricular septum leads to a significant decrease in right ventricular function. Maintaining left ventricular developed pressure and hence the contribution of the interventricular septum to right ventricular function may be important in the management of right ventricular failure. PMID- 11782759 TI - Improved right heart function after myocardial preservation with 2,3-butanedione 2-monoxime in a porcine model of allogenic heart transplantation. AB - BACKGROUND: Right heart dysfunction is a major cause for early morbidity and mortality after heart transplantation. Experiments were designed to evaluate the influence of the calcium-desensitizing drug 2,3-butanedione 2-monoxime (BDM) on right heart function in a porcine model of heart transplantation. METHODS: Donor hearts of domestic pigs were arrested with BDM in Krebs solution (n = 7) and with BDM in Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution (n = 6). There were 2 control groups: University of Wisconsin (UW, n = 6) and HTK (n = 6). An isovolumic model was used in which the right ventricular volume was precisely controlled in vivo with an intracavitary high-compliance balloon. After 4 hours of ischemia, hearts were transplanted into recipients. After 1 and 2 hours of reperfusion, the right ventricular balloon volume was increased in 10-mL increments until right ventricular failure occurred and the developed pressures were recorded. RESULTS: Maximal right ventricular developed pressures were significantly different after 2 hours of reperfusion (UW: 35 +/- 13 mm Hg; HTK: 47 +/- 8 mm Hg; Krebs+BDM: 49 +/- 9 mm Hg; HTK+BDM: 50 +/- 6 mm Hg; P =.04). Hearts subjected to BDM could be loaded with a significantly increased volume after 1 hour and after 2 hours (UW: 57 +/- 10 mL vs HTK: 43 +/- 8 mL vs Krebs+BDM: 70 +/- 10 mL vs HTK+BDM: 67 +/- 15 mL; P =.002). Postischemic right ventricular enddiastolic compliance was significantly increased in groups treated with BDM after 1 hour (P =.02) and after 2 hours (P =.039). CONCLUSIONS: The drug BDM significantly improves right ventricular function in a heart transplantation model. The increase in volume load and developed right ventricular pressure achieved by BDM application would translate into a decreased risk of right ventricular failure after clinical transplantation. PMID- 11782760 TI - Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy. AB - OBJECTIVE: Hypertrophic obstructive cardiomyopathy has been proposed to be the result of gene mutations of contractile proteins. However, we have previously shown significant elevation of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) at the messenger RNA, protein, and receptor levels in patients with hypertrophic obstructive cardiomyopathy when compared with myocardium from patients without this disorder. We hypothesized that this growth factor overexpression is a regional phenomenon. To test this hypothesis, we compared levels of IGF-I and TGF-beta1 in hypertrophic and nonhypertrophic myocardium within the same group of patients with hypertrophic obstructive cardiomyopathy. METHODS: Two biopsy specimens were obtained from each patient undergoing septal myectomy for severely symptomatic hypertrophic obstructive cardiomyopathy, from hypertrophied septum and from nonhypertrophied myocardium (8 patients in total). Clinical data were prospectively recorded. Messenger RNA levels for growth factor were quantified by means of multiplex reverse transcriptase-polymerase chain reaction, expressed as a densitometric ratio of growth factor/glyceraldehyde-3-phosphate dehydrogenase. Protein levels were quantified by means of chemiluminescent slot blot analysis. Growth factor proteins were used to generate a standard curve. RESULTS: IGF-I messenger RNA and protein levels in hypertrophic myocardium were 2.6 and 2.9 times greater, respectively, than in nonhypertrophic myocardium of the same patients (both P <.01). TGF-beta 1 messenger RNA and protein levels in the hypertrophic myocardium were 2.5 and 2.8 times greater, respectively, than the levels in the nonhypertrophied myocardium (both P <.01). There was a significant correlation between the IGF-I protein ratio (hypertrophic/nonhypertrophic myocardium) and the inducible left ventricular outflow tract gradients measured at cardiac catheterization (r = 0.77, P =.025). CONCLUSIONS: Myocardial overexpression of IGF-I and TGF-beta1 is a regional phenomenon in patients with hypertrophic obstructive cardiomyopathy and is likely involved in the pathogenesis of the disorder. PMID- 11782761 TI - Totally endoscopic mitral valve repair. PMID- 11782762 TI - Surfactant function in lung transplantation after 24 hours of ischemia: advantage of retrograde flush perfusion for preservation. AB - OBJECTIVE: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. METHODS: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. RESULTS: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO(2)/FIO(2) (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. CONCLUSION: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group. PMID- 11782763 TI - Experimental study on size matching in a canine living-donor lobar lung transplant model. AB - OBJECTIVE: In an effort to address the donor-shortage issue, living-donor lobar lung transplants have been performed with satisfactory results. The use of small grafts is potentially problematic because it could cause high pulmonary artery pressure, resulting in lung edema. The purpose of this study was to evaluate the effect of small grafts on early pulmonary function and to identify the predictor for acceptable size discrepancy. METHODS: Seventeen pairs of mongrel dogs with various donor-recipient sizes were used. Body weight, height, chest circumference, and lung weight were measured as size parameters. Right middle, lower, and cardiac lobes were implanted as a right lung of the recipient and the left lower lobe was implanted as a left lung without use of cardiopulmonary bypass. Pulmonary function of the recipient was measured for 6 hours after reperfusion. RESULTS: A significant negative correlation was found between donor/recipient body-weight ratio and mean pulmonary artery pressure at 1 hour (r = -0.594, P =.025). A significant correlation was found between donor/recipient body-weight ratio and PaO(2) at 6 hours (r = 0.704; P =.007). There was no significant correlation between the other 3 size parameters and postoperative pulmonary function. All 8 recipients with a donor/recipient body-weight ratio of 1.2 or greater survived the 6-hour assessment period, and their PaO(2) exceeded 500 mm Hg at 6 hours. CONCLUSIONS: Donor/recipient weight ratio is an important predictor of early pulmonary function in a canine living-donor lobar lung transplant model. PMID- 11782764 TI - Consensus-based method for risk adjustment for surgery for congenital heart disease. AB - OBJECTIVE: The aim was to develop a consensus-based method of risk adjustment for in-hospital mortality among children younger than 18 years after surgery for congenital heart disease (designated RACHS-1). METHODS: An 11-member national panel of pediatric cardiologists and cardiac surgeons used clinical judgment to place surgical procedures into six risk categories. Categories were refined after review of information from the Pediatric Cardiac Care Consortium and three statewide hospital discharge data sets. The effects of including additional clinical variables were explored by comparing areas under receiver-operator characteristic curves. RESULTS: Among 4602 surgical patients in the Pediatric Cardiac Care Consortium data set and 4493 in the hospital discharge data, 3767 (81.9%) and 3832 (85.3%), respectively, had a single cardiac procedure, and 98.5% and 89.2%, respectively, were able to be assigned to one of six risk categories defined by the panel. Mortality rates showed expected trends (P <.001). For the Pediatric Cardiac Care Consortium data, mortality rates were 0.4% in category 1, 3.8% in 2, 8.5% in 3, 19.4% in 4, and 47.7% in 6; rates were similar in the hospital discharge data. There were too few cases in category 5 to estimate mortality rates. In multivariable models, younger age, prematurity, and the presence of a major noncardiac structural anomaly added to the risk of in hospital death predicted by risk category alone. Best performance was obtained when cases with multiple procedures were placed in the risk category of the most complex procedure. CONCLUSION: The RACHS-1 method should adjust for baseline risk differences and allow meaningful comparisons of in-hospital mortality for groups of children undergoing surgery for congenital heart disease. PMID- 11782766 TI - Use of extracorporeal membrane oxygenation in pediatric thoracic organ transplantation. AB - OBJECTIVE: Mechanical cardiorespiratory support is occasionally required before or after pediatric thoracic organ transplantation. Extracorporeal membrane oxygenation is the most commonly used mechanical support technique in children. The goal of this study was to examine the indications for initiation and outcomes after peritransplant use of extracorporeal membrane oxygenation. METHODS: A retrospective study was conducted of 65 patients who received peritransplant extracorporeal membrane oxygenation between November 1994 and June 2000. The pretransplant group included 45 patients (average age, 38 months) supported with extracorporeal membrane oxygenation and listed for transplantation (31 heart, 8 lung, and 6 heart-lung), and the post-transplant group included 20 patients (average age, 83 months) who required extracorporeal membrane oxygenation after thoracic organ transplantation (12 heart, 6 lung, and 2 heart-lung transplants). Hospital course and outcomes were evaluated. RESULTS: With regard to pretransplant extracorporeal membrane oxygenation, patients listed for heart transplants were more likely to survive to transplantation than were those listed for lung or heart-lung transplants (12/31 [39%] vs 1/14 [7%], P =.03). There was no difference in long-term survival between heart transplant patients after extracorporeal membrane oxygenation and those without extracorporeal membrane oxygenation (12-month actuarial survival, 83% vs 73%; P =.68). Patients who survived for prolonged periods on extracorporeal membrane oxygenation (>250 hours) typically received heart transplants (7/8 [88%]). With regard to post transplant extracorporeal membrane oxygenation, patients receiving lung or heart lung transplants had better short-term outcomes than those receiving heart transplants (63% survived to discharge vs 33%). All 3 patients with early graft dysfunction receiving lung transplants survived to discharge. CONCLUSIONS: Long term outcomes among those undergoing heart transplantation after support with an extracorporeal membrane oxygenator are comparable with those of patients not receiving extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation can be a useful post-transplant support device, particularly in patients undergoing lung transplants. PMID- 11782765 TI - Delivery of a non-potassium modified maintenance solution to enhance myocardial protection in stressed neonatal hearts: a new approach. AB - OBJECTIVES: This study was undertaken to compare conventional cardioplegic strategies with a new approach that uses a modified non-potassium maintenance solution between cardioplegia doses in stressed neonatal hearts. METHODS: Thirty five neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass. In 10 animals bypass was discontinued without further ischemia (stress control group). The other 25 received a warm blood cardioplegic induction and were separated into 5 groups. In 5 animals cardiopulmonary bypass was discontinued without further ischemia (cardioplegia control group); the remaining 20 underwent an additional 70 minutes of cold blood cardioplegic arrest. Five received only intermittent cardioplegia every 20 minutes, whereas 15 also received cold blood maintenance infusions between cardioplegic doses (integrated strategy). In 5 of these animals the blood was unmodified, whereas in 10 a modified non-potassium "cardioplegia-like" solution was delivered either antegradely (n = 5) or retrogradely (n = 5). Myocardial function was assessed by pressure-volume loops (expressed as percentage of control); vascular function was assessed by coronary vascular resistance. RESULTS: All piglets that underwent hypoxic ischemic stress alone (controls) died. Warm induction alone (cardioplegic controls) partially repaired the stress injury. Intermittent cardioplegia preserved the depressed systolic function (end-systolic elastance 40% vs 39%), increased diastolic stiffness (255% vs 239%), reduced adenosine triphosphate (10.6 vs 12.2 microg/g tissue), and elevated coronary vascular resistance at levels identical to warm induction alone; infusing unmodified blood between cardioplegia doses (standard integrated) improved results slightly. In contrast, infusion of a cold modified solution (antegrade or retrograde) between cardioplegia doses (modified integrated) completely restored systolic function (end-systolic elastance 100% and 97%, P <.001 vs intermittent and standard integrated), only minimally increased diastolic stiffness (159% and 156%, P <.001 vs intermittent and standard integrated), restored adenosine triphosphate (18.8 and 16.6 microg/g, P <.001 vs intermittent and standard integrated), and normalized coronary vascular resistance (P <.001 vs intermittent and standard integrated). This strategy was used in 72 consecutive hypoxic patients (21 arterial switch operations, retrograde; 51 Fontan procedures, antegrade) with a 2.8% mortality. CONCLUSIONS: Infusion of a cold modified solution between cardioplegic doses (modified integrated protection) significantly improved myocardial protection in the stressed neonatal heart, was effective delivered either antegradely or retrogradely, and was used successfully for hypoxic (stressed) pediatric patients. PMID- 11782767 TI - Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children. AB - OBJECTIVES: Ischemia-reperfusion injury after cardiopulmonary bypass is known to provoke an inflammatory response, which can be attenuated with steroid pretreatment. Cardiopulmonary bypass is also known to stimulate apoptosis. Induction of the cellular apoptotic cascade occurs via interaction between two membrane receptors: Fas and Fas ligand. Both molecules also exist in soluble forms, whose significance remains undetermined; however, both may have a proinflammatory role. We aimed to document the temporal profile of soluble Fas and soluble Fas ligand after cardiopulmonary bypass and to investigate whether steroid pretreatment alters this response. METHODS: The study was of a non randomized, non-blinded, prospective nature. Twenty-seven infants were monitored prospectively, of whom 13 received dexamethasone at induction of anesthesia. Soluble Fas, soluble Fas ligand, and interleukin 6 were measured from induction of anesthesia until 24 hours after admission to the intensive care unit. Data on clinical and laboratory variables were also collected at the same time intervals. RESULTS: As expected, dexamethasone pretreatment attenuated interleukin 6 release and the clinical systemic inflammatory response after bypass. Soluble Fas showed a remarkably similar profile to interleukin 6, in terms of temporal release and attenuation with steroids. There was also a correlation between maximum soluble Fas and markers of capillary leak (colloid requirement and drain loss). Conversely, soluble Fas ligand release was unchanged by cardiopulmonary bypass and steroid administration. However, patients with higher soluble Fas ligand levels exhibited a more dramatic drop and delayed recovery in monocyte count, consistent with the role of this molecule in apoptosis. CONCLUSIONS: Release of soluble Fas and soluble Fas ligand follows a markedly different temporal profile after cardiopulmonary bypass. The similarity between soluble Fas and interleukin 6, together with the attenuation of both with steroids, may suggest a role for soluble Fas as a proinflammatory marker. PMID- 11782768 TI - Management of congenital tracheal stenosis by means of slide tracheoplasty or resection and reconstruction, with long-term follow-up of growth after slide tracheoplasty. AB - OBJECTIVE: The difficult problem of congenital tracheal stenosis is infrequent and has been managed with several methods. Patch tracheoplasty has been favored in recent years. Alternative experience with a simpler program of slide tracheoplasty for long-segment stenosis or resection and reconstruction for short segment stenosis is described and proposed as preferable. Long-term growth after slide tracheoplasty was studied. METHODS: Eleven consecutive patients aged 10 days to 23 years with varied patterns of stenosis (including concurrent pulmonary artery sling, anomalous right upper lobe bronchus, and bridge bronchus) had their stenoses corrected, 8 by means of slide tracheoplasty and 3 by means of resection and anastomosis. Retrospective review was made of hospital course, complications, and long-term results, with observation of growth in 4 patients (from more than 1(1/2)-7(3/4) years). RESULTS: All patients are alive and enjoy good airways. Only 3 patients who needed concomitant cardiovascular procedures and 1 with poor ventricular function required bypass. Eight were extubated immediately or on the day of the operation, 1 at 3 days, and 1 at 8 days. A patient with complex anomalies needed 10 days of ventilation. Three had anastomotic granulomas successfully treated by means of a single bronchoscopy. Long-term airway growth was entirely satisfactory after slide tracheoplasty in 4 infants and small children (aged 10 days, 3 months, 6 months, and 3(1/2) years, respectively). CONCLUSIONS: Slide tracheoplasty gives excellent short- and long-term results because long congenital stenosis is reconstructed with native tracheal tissue and is therefore immediately stable and lined with normal epithelium, and the operation is accomplished more simply and with a generally more benign postoperative course. Wholly satisfactory growth of the repaired segment occurs. Less common short congenital stenosis is effectively managed with resection and anastomosis. PMID- 11782769 TI - Successful allotransplantation of cryopreserved tracheal grafts with preservation of the pars membranacea in nonhuman primates. AB - OBJECTIVE: This study was performed to confirm the feasibility of cryopreserved tracheal allotransplantation in primates, the anatomy and immunology of which are considered to be more closely related to those of humans than those of other animals. METHODS: Cryopreserved tracheal allotransplantations were performed in 3 recipient primates. In the control group fresh tracheal allotransplantations were performed in 2 primates (control A), and a tracheal allotransplantation with a simply frozen tracheal graft was performed in 1 primate (control B). Monthly bronchoscopic examinations, histologic examinations, electron microscopic examinations, and immunohistochemical investigations were performed in each of the primates. RESULTS: In the cryopreserved tracheal allotransplantation group, 3 recipient monkeys were killed on the 35th, 144th, and 387th postoperative days, respectively. All grafts were incorporated by the recipient trachea without stenosis in the cryopreserved group. In the control group 2 recipient monkeys were killed on the 93rd postoperative day (control A), and one was killed on the 84th postoperative day (control B). Severe stenosis was observed after the transplantation in all of the control monkeys. Immunologic reactions appeared to be attenuated by the cryopreservation, whereas T cell-mediated immunologic rejection (control A) and loss of cartilage viability (control B) were considered to be the causes of graft failure in the control group. CONCLUSION: The immunogenicity of the tracheal allografts was reduced by cryopreservation, and cryopreserved tracheal allotransplantation was successful in our primate model. Further investigation of cryopreserved tracheal allotransplantation with regard to proper clinical applications and the limitations of the procedure should be performed. PMID- 11782770 TI - New tubular bioabsorbable knitted airway stent: biocompatibility and mechanical strength. AB - OBJECTIVE: This study examines the biocompatibility and suitability of a new tubular bioabsorbable knitted stent made of poly-L -lactic acid in normal rabbit airways and examines the mechanical strength of this stent in vitro. METHODS: A tubular knitted airway stent (group B, n = 15) made of poly-L -lactic acid wire was implanted operatively in New Zealand White rabbits intratracheally; silicone stents served as controls (group A, n = 8). The cervical trachea was exposed, and the stent was implanted. Up to 40 weeks after stent implantation, the rabbits were killed, at which time bronchoscopy, histologic examination, and scanning electron microscopic study was done. We tested poly-L -lactic acid stents and silicone stents for their mechanical strength in vitro. We subjected stents to area loads and measured their mechanical strengths. RESULTS: In group A, which received silicone stents, 3 (37.5%) rabbits died within 4 weeks of stent implantation as a result of airway obstruction by secretions inside the stent lumen. In group B, poly-L -lactic acid stents, 1 (6.7%) rabbit died 3 weeks after implantation because of weakness caused by anorexia. In the remaining animals, except for 1 animal with stent trouble, the bronchial lumen was fully open until the 40th week after implantation. After 40 weeks of follow-up, the stents disappeared, except for nonabsorbable suture in the bronchial wall. None of the animals in group B died of airway complication. Histologic examination and scanning electron microscopic examination of the group A silicone stents showed marked regression of ciliated cells under the stent. In group B the ciliated epithelium was preserved, and there were numerous capillary blood vessels in the submucosa. In scanning electron microscopy of the group B poly-L -lactic acid stents, the ciliated cells were preserved between the mesh holes of the stent. For diameters between 4 and 6 mm, the mechanical strength of silicone stents was greater than that of poly-L -lactic acid stents. However, the mechanical strength of poly-L -lactic acid stents increased as a function of their diameter. CONCLUSION: A new tubular bioabsorbable stent made of poly-L -lactic acid is biocompatible in normal rabbit airways, indicating that poly-L -lactic acid is a promising material for airway stents for clinical use. PMID- 11782771 TI - Enhancement of Apo2L/TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in non-small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein. AB - OBJECTIVE: Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer drug that promotes apoptosis specifically in tumor cells. Because not all cancer cells are susceptible to Apo2L/TRAIL, the aim of our study was to determine whether non-small cell lung cancer cells can be sensitized by chemotherapeutic agents for Apo2L/TRAIL-induced apoptosis. In addition, endogenous expression levels of the caspase-inhibiting cellular protease caspase-8 inhibitory protein (C-FLIP) were measured to investigate partial resistance to Apo2L/TRAIL. METHODS: Six human lung cancer cell lines (A549, NCI-H358, Calu1, Calu6, SkMes1, and SkLu1) were incubated with soluble Apo2L/TRAIL and two different concentrations each of cisplatin, paclitaxel, doxorubicin, 5-fluorouracil, and camptothecin. After 24 hours the rate of apoptosis was measured by annexin V/propidium iodide staining followed by FACScan analysis. Expression levels of C-FLIP in cell lines and lung cancer biopsy specimens were determined by Western blotting. RESULTS: Treatment of lung cancer cells with Apo2L/TRAIL alone resulted in apoptotic cell death in four cell lines (P <.001). Combining Apo2L/TRAIL and chemotherapeutic agents enhanced the rate of apoptosis significantly. Statistical analysis revealed a synergistic effect of Apo2L/TRAIL in combination with 1.8 mmol/L camptothecin and 100 micromol/L cisplatin, each in four of the six cell lines (P <.002). Western blot analysis showed that sensitization to Apo2L/TRAIL did not correlate with the expression of cellular protease caspase-8 inhibitory protein. Furthermore, no increased cellular protease caspase-8 inhibitory protein levels relative to those in normal lung tissue could be found in non-small cell lung cancer specimens from 12 patients. CONCLUSION: Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cell lines is significantly enhanced by chemotherapeutic agents. Resistance and sensitization to Apo2L/TRAIL are not correlated with the endogenous expression level of cellular protease caspase-8 inhibitory protein, implying that in non small cell lung cancer other mechanisms are responsible for inhibition of the Apo2L/TRAIL pathway. Even though the molecular mechanism remains unclear, the combination of Apo2L/TRAIL with chemotherapy may be a promising treatment modality for non-small cell lung cancer. PMID- 11782772 TI - Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy. AB - OBJECTIVES: Some patients and oncologists choose to treat localized esophageal cancer with definitive chemotherapy and radiation therapy rather than surgery. A subset of these patients have local relapse without distant metastases and therefore have no other curative intent treatment option but salvage esophagectomy. METHODS: We reviewed our experience with salvage esophagectomy from 1987 to 2000 at M.D. Anderson Cancer Center (n = 13, salvage after chemotherapy and radiotherapy group) and compared the data with those of patients receiving esophagectomy in a planned fashion 4 to 6 weeks after preoperative chemotherapy and radiation therapy (n = 99, preoperative chemotherapy and radiotherapy group). RESULTS: Increases in morbidity were seen after resection in the salvage after chemotherapy and radiotherapy group relative to the preoperative chemotherapy and radiotherapy group: mechanical ventilation (9.0 days vs 3.3 days, P =.08), intensive care unit stay (11.2 days vs 5.1 days, P =.07), hospital stay (29.4 days vs 18.4 days, P =.03), and anastomotic leak rates (5/13 [39%] vs 7/99 [7%], P =.005). Operative mortality (within 30 days) also tended to be increased statistically nonsignificantly (2/13 [15%] vs 6/99 [6%], P =.2). Salvage esophagectomy resulted in long-term survival (25% 5-year survival) in a subset of patients. Improved survival after salvage esophagectomy was associated with early pathologic stage (T1 N0, T2 N0), prolonged time to relapse, and R0 surgical resection. CONCLUSION: Patients who undergo salvage esophagectomy for relapse of tumor after definitive chemoradiation therapy have increased morbidity, mortality, and hospital use relative to patients undergoing planned esophagectomy after preoperative chemoradiation. Nevertheless, long-term survival can be achieved in this group, and such treatment should be considered for carefully selected patients at an experienced center. PMID- 11782773 TI - Extrapleural pneumonectomy for lung cancer with carcinomatous pleuritis. PMID- 11782774 TI - Extensive corrosive injuries of the upper airways and gastrointestinal tract. PMID- 11782775 TI - Extralobar infradiaphragmatic pulmonary sequestration with a digestive communication. PMID- 11782776 TI - Intrathoracic jugular vein avulsion after blunt chest trauma. PMID- 11782777 TI - Rastelli repair for transposition of the great arteries: Still the best choice? PMID- 11782778 TI - Fistulectomy for pulmonary arteriovenous fistula: historical context. PMID- 11782779 TI - Normothermic cardiopulmonary bypass in pediatric surgery. PMID- 11782780 TI - Neurologic complications after radial artery harvesting. PMID- 11782781 TI - Effect of substance P on intravenous self-administration of morphine in different rat strains. AB - We studied the effects of substance P on intravenous self-administration of morphine in WAG/G and Fischer-344 rats. By the end of week 2 the daily amount of self-administered morphine in WAG/G rats was higher than in Fischer-344 rats. Treatment with substance P markedly suppressed self-injection of morphine, particularly in low doses. The most pronounced effects were observed in Fischer 344 rats. Substance P did not change food-procuring behavior of animals in the same experimental chambers. Since the content of substance P in the hippocampus, hypothalamus, and midbrain of Fischer-344 rats is much lower than in WAG/G rats, and morphine addiction in Fischer-344 rats is less pronounced than in WAG/G rats, the degree of opiate addiction is not determined by the content of substance P in rat brain. However, in our experiments treatment with substance P abolished morphine addiction, particularly in animals with low content of this compound in the brain. PMID- 11782782 TI - Relationships between venous return and blood pressure in caval veins and right atrium during pressor stimulation. AB - The dynamics of changes in blood flow and pressure in the superior and inferior vena cava, total venous return, and right atrial pressure in response to pressor stimuli were studied in acute experiments on cats. It was shown that blood flow and pressure in caval veins changed synchronously and unidirectionally, while shifts in the right atrial pressure did not depend on direction and magnitude of changes in caval flow and pressure and total venous return. Our results suggest that right atrial pressure does not play a role in the regulation of venous return. PMID- 11782783 TI - Effect of amylin on mast cell secretion as a possible mechanism increasing gastric mucosa resistance. AB - Water-immersion restraint stress increased secretory activity of mast cells and led to the formation of erosive lesions in the gastric mucosa. Intraperitoneal administration of amylin in a dose of 0.5 microg/kg 1 h before stress suppressed degranulation of mast cells and decreased the severity of gastric mucosa damages. In in vitro experiments amylin abolished the activating effects of acetylcholine and bradykinin on mast cell degranulation. Amylin-induced stabilization of activated mast cells probably underlies its protective effects during ulceration. PMID- 11782784 TI - Effect of amylin on the tone of rat aorta ring preparation. AB - Amylin (10(-10)M) induced relaxation of norepinephrine-precontracted rat aortic rings by more than 50%. This effect was preserved after blockade of NO-synthase and even after denudation of the vessel. Thus amylin-induced vasodilation is an endothelium-independent process not mediated by NO. PMID- 11782785 TI - Interrelation between different stages of atherogenesis in rabbits with high and low resistance to dyslipidemia. AB - Changes in lipid metabolism and morphofunctional state of neuroregulatory and circulatory systems during dyslipidemia were studied in rabbits with high and low resistance to this risk factor. It was found that impairment of neuroregulatory systems plays an important role in initiation and progression of microcirculatory disorders and atherosclerosis. Atherogenic index is the most informative parameter for evaluation of pathological changes in the vascular system during dyslipidemia. PMID- 11782786 TI - Postresuscitation changes in neuronal hippocampal populations in rats with different learning ability. AB - The state of pyramidal cell populations in CA1 and CA4 hippocampal fields was studied in resuscitated and intact rats with different learning ability. Morphometry showed that postresuscitation damage to neurons was more pronounced in good learners compared to poor learners. Interferometry revealed higher protein content in neurons in poor learners compared to successfully trained rats. It was hypothesized that different neuronal resistance to ischemia in rats characterized by different learning ability is determined by some peculiarities in protein metabolism preexisting in intact animals and manifesting in the postresuscitation period. PMID- 11782787 TI - Changes in the antioxidant state and intensity of lipid peroxidation in the blood and liver during 30-day hypokinesia. AB - Thirty-day hypokinesia was accompanied by an increase in plasma antioxidant activity and inactivation of liver antioxidant enzymes. The observed activation of blood antioxidant enzymes during hypokinesia was associated with increased resistance to acute hypoxic hypoxia. PMID- 11782788 TI - Course of shock in rats with different resistance to shockogenic trauma during Crush syndrome. AB - Experiments on narcotized rats with crush syndrome showed that low resistant animals developed pronounced hypovolemia, hemoconcentration, blood hyperviscosity, impairment of oxygen metabolism, and central and peripheral hemodynamic disturbances, whereas in highly resistant rats the hemodynamics and oxygen supply to tissues were maintained at a sufficient level, while hemoconcentration and the increase in blood viscosity were less pronounced. PMID- 11782789 TI - Effect of transplantation of human fetal tissues on prooxidant-antioxidant equilibrium in the liver and blood rats after partial hepatectomy in rats. AB - We studied the effect of transplantation of fetal liver cells and postnuclear cytoplasmic fraction from human fetal soft tissues on the prooxidant-antioxidant equilibrium in the liver and blood of rats after partial hepatectomy. The preparations increased antioxidant activity and decreased the intensity of lipid peroxidation, which probably contributes to their therapeutic effects. PMID- 11782790 TI - Isolation of toxins from Buthus occitanus sp. scorpion and their action on excitability of myelinated nerve. AB - A series of short neurotoxins (molecular weight 3500-5000 D) was isolated from Vietnamese scorpion B. occitanus sp. All these toxins blocked generation of action potentials (this effect depended on their molecular weight), but did not change conduction velocity and excitation threshold of the nerve. PMID- 11782791 TI - Inhibitor of beta-hydroxy-beta-methylglutaryl coenzyme A reductase decreases energy supply to the myocardium in rats. AB - Hypocholesterolemic preparations, inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl coenzyme A reductase (statins), block the synthesis of ubiquinone Q10, intermediate electron carrier in the mitochondrial respiratory chain. This should decrease energy supply to tissues. Daily peroral administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor simvastatin (24 mg/kg perorally) for 30 days had no effect on the contents of macroergic phosphates (ATP and creatine phosphate) in the liver, but decreased these parameters in the myocardium. PMID- 11782792 TI - Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration. AB - Experiments on rats trained passive avoidance task showed that N-phenyl-acetyl-L prolyl-glycyl ethyl ester, peptide analog of piracetam (GVS-111, Noopept) after oral administration retained antiamnesic activity previously observed after its parenteral administration. Effective doses were 0.5-10 mg/kg. Experiments on a specially-developed model of active avoidance (massive one-session learning schedule) showed that GVS-111 stimulated one-session learning after single administration, while after repeated administration it increased the number of successful learners among those animals who failed after initial training. In this respect, GVS-111 principally differs from its main metabolite cycloprolylglycine and standard nootropic piracetam. PMID- 11782793 TI - Modification of humoral immune response in C57Bl/6 mice with a complex of alpha fetoprotein and retinoid acid derivatives. AB - Amides of all trans-retinoic acid and O-phospho-L-threonine, O-phospho-L tyrosine, and O-phosphoethanolamine injected intravenously in a dose of 6.8 microg/kg 1.5-3.4-fold increased the count of antibody-producing cells in the spleen of C57Bl/6 mice (primary immune response to sheep erythrocytes). Activity of the complex containing alpha-fetoprotein and L-threonine ligand did not differ from that of free retinoid. This complex holds much promise as a prototype of immunomodulators with a wide range of activity. PMID- 11782794 TI - Role of activation of the sympathoadrenal system in the realization of immune reactions during acute poisoning with organophosphorus compounds. AB - Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyldichlorovinylphosphate (0.2 and 0.8 LD50) was accompanied by suppression of the major immune reactions. Increasing the concentration of epinephrine and norepinephrine in the plasma produced less pronounced opposite effects, except for the influence on natural killer activity. PMID- 11782795 TI - Modulatory effects of autologous plasma on functional activity of human immunocompetent cells. AB - Blast transformation of peripheral blood lymphocytes stimulated with phytohemagglutinin and concanavalin A was studied in children with pyelonephritis and glomerulonephritis. Activity of natural killer cells from children with pyelonephritis was estimated before and after treatment with 50% autologous plasma. The autologous plasma modulated blast transformation of lymphocytes and activity of natural killer cells, which depended on the stage of diseases. PMID- 11782797 TI - Modulation of exploratory behavior in mice during activation of cell immune response. AB - We revealed a modulating effect of cell immune response on exploratory activity of (CBA degrees C57Bl/6)F1 mice depending on their initial behavioral profile. The formation of BCG-induced delayed-type hypersensitivity was accompanied by stimulation of the exploratory behavior in animals with initially low or intermediate activity, but did not change this parameter in behaviorally active mice. PMID- 11782796 TI - Effects of low-molecular-weight thymic RNA on T cell-dependent antibody formation. AB - We proposed a method for isolation of low-molecular-weight RNA from mammalian thymus. Physicochemical properties and regulatory activity of these RNA in immunological test of T cell-dependent antibody formation were evaluated. PMID- 11782798 TI - Regulation of type 1 pili expression as exemplified by Escherichia coli strain m17. AB - Studies of E. coli strain M17 colibacterin and its derivatives showed that fimH gene regulates morphological characteristics of type 1 fimbria and cell piliation on the whole. Gene fimH has a negative effect and decreased the percentage of piliated cells in the population and piliation of individual cells, which does not agree with its role of a positive regulator. PMID- 11782799 TI - Effects of type 1A serotonin receptor agonist 8-OH-DPAT on immune response. AB - The selective agonist of type 1 A serotonin receptors 8-hydroxy-2-(di-n-propyl amino)tetra-lin (8-OH-DPAT) suppressed the immune response. Intraperitoneal administration of 1 mg/kg 8-OH-DPAT to Wistar rats over 2 days after immunization decreased the count of plaque- and rosette-forming cells on day 5. Our results indicate that type 1A serotonin receptors are involved in the realization of the immunosuppressive effects of the serotoninergic system. PMID- 11782800 TI - Immunosorbent for removal of b2-microglobulin from human blood plasma. AB - Immunosorbent removing beta2-microglobulin from human blood plasma was synthesized on the basis of sheep monospecific polyclonal antibodies to beta2 microglobulin and conditions ensuring effective regeneration of the immunosorbent for its repeated use were selected. Relationships between adsorption capacity and the volume of immobilized ligand, antigen concentration in the solution, and duration of incubation were studied. The adsorbent can be used for effective and specific removal of beta2-microglobulin from the plasma of patients on chronic hemodialysis. PMID- 11782801 TI - Effects of hydrocortisone on peritoneal phagocytizing cells in rats under conditions of beta-adrenoceptors blockade. AB - Hydrocortisone decreased the count of peritoneal mononuclear phagocytes and mast cells and total phagocytic activity of peritoneal phagocytes in rats, but had no effect on the nitroblue tetrazolium test. beta-Adrenoceptor blockade abolished the suppressive effect of hydrocortisone on phagocytosis and prevented the decrease in the count of mast cells, but markedly reduced the number of neutrophils and parameters of stimulated nitroblue tetrazolium test. PMID- 11782802 TI - Soluble Fas antigen (sFAS) in the serum from patients with adrenal tumors. AB - Serum content of soluble Fas antigen was measured by enzyme immunoassay in 60 healthy donors, 31 patients with adrenal tumors, and 16 patients with diffuse-and nodular hyperplasia of the adrenal cortex accompanying primary aldosteronism and Cushing's disease. sFas was more often detected in the serum from patients with tumors of the adrenal cortex and medulla and diffuse-and-nodular hyperplasia of the adrenal cortex and its content varied in a wider range in patients compared to healthy donors. No correlations were found between the incidence of sFas, its content, sex, and age of healthy donors and patients. The highest content of sFas was found in patients with pheochromocytoma and primary aldosteronism. sFas probably plays a role in the pathogenesis of adrenal tumors and hyperplasia. PMID- 11782803 TI - Effect of a novel antineoplastic drug olipifat on antitumor immunity in mice. AB - Olipifat is an antineoplastic drug containing pyrophosphate and a product of special lignin processing. Donor C57Bl/6J mice with syngeneic B16 melanoma received a single 5-day course of olipifat. Effect of olipifat on antitumor resistance was evaluated by local neutralization test [3]. In animals with rapid melanoma growth, splenic cells from intact donors stimulated tumor growth. Olipifat abolished this growth-stimulating effect of splenocytes. In animals with slow melanoma growth, splenocytes had no effect on the growth of melanoma or Lewis lung cancer. In this case, splenocytes from olipifat-treated donors completely arrested the growth of melanoma B16 and decelerated the growth of Lewis lung carcinoma. PMID- 11782804 TI - Peculiarities of carnosine metabolism in a patient with pronounced homocarnosinemia. AB - The article describes a case of homocarnosinemia with increased liquor and plasma content of homocarnosine, increased urinary excretion of homocarnosine, and low activity of serum carnosinase. These metabolic disturbances were accompanied by moderate neurological disorders. Changes in carnosine metabolism in family members were less pronounced and not accompanied by neuropathological symptoms. PMID- 11782805 TI - Transplantation of cultured human neural progenitor cells into rat brain: migration and differentiation. AB - We studied the fate in vitro cultured human stem/progenitor cells after transplantation into rat brain. The cells from human fetuses at 8-12 weeks' gestation were cultured in vitro for 14 days and transplanted into the brain of 10-day-old and adult rats. Microscopic examination showed that human stem/progenitor cells migrated into various regions of rat brain. Immunohistochemical assay demonstrated that some cells differentiated into astrocytes and neurons, while others retained the embryonic phenotype. PMID- 11782806 TI - Pathomorphological peculiarities of microcirculatory bed in bronchial wall in workers employed in mining and chemical industry. AB - Morphological alterations of microvessels in bronchial mucosa and blood capillaries of alveolar septa during endobronchitis were examined in workers employed at a plutonium plant and not employed residents (Zheleznogorsk, Krasnoyarsk Region). Alterative, destructive, and dysadaptive changes in pulmonary vessels of workers were paralleled by developing reparative and adaptive processes in neighboring capillaries. PMID- 11782807 TI - Structural and metabolic characteristic of nephrocytes during peritonitis of various genesis. AB - Structural and metabolic changes in nephrocytes during peritonitis were studied on early autopsy material. Unspecific morphological changes in the kidneys were presented by circulatory disturbances and damage to the tubular epithelium. The changes in dehydrogenase activity in nephrocytes of the proximal and distal tubules depended on the cause of peritonitis. PMID- 11782808 TI - Ultrastructural changes in erythrocytes in patients with mental disorders. AB - Transmission electron microscopy of peripheral blood erythrocytes from patients with paranoid and residual schizophrenia, mental retardation, and neurotic disturbances revealed nonspecific ultrastructural changes in the membrane and matrix of red blood cells. PMID- 11782809 TI - Ischemia-induced changes in synaptoarchitectonics of brain cortex and their correction with ascovertin and Leuzea extract. AB - Peroral administration of 70 mg/kg ascovertin and 150 mg/kg Leuzea extract to rats with cerebral ischemia for 5 days prevented destructive changes and decrease in the density of synapses in the cerebral cortex. These preparations activated compensatory and reparative mechanisms underlying plasticity of the synaptic pool, which was realized through hypertrophy and destruction of synaptic contacts. Ascovertin possessed more pronounced cerebroprotective activity than Leuzea extract. PMID- 11782810 TI - Morphological changes in myocardium in rats with different resistance to hypoxia after ligation of the coronary artery. AB - We studied morphological changes in the myocardium during experimental myocardial infarction in rats with different resistance to hypoxia. Microscopic examination showed that morphological changes in the ischemic zone and adjacent tissues are different in rats with high and low resistance to acute ischemia. In highly resistant rats, necrotic changes in cardiomyocytes included focal contracture and loosening. These changes were followed by the formation of focal necroses with well-defined boundaries, dense demarcation infiltrates, and pronounced hypertrophy of cardiomyocytes in the adjacent tissue. In low resistant rats, pronounced edema in the ischemia zone and numerous hemorrhages in the interstitial tissue developed in the early stage after coronary occlusion. These changes were followed by the formation of more extensive necrotic areas with diffuse boundaries, less pronounced demarcation, and irregular hypertrophy of cardiomyocytes in the surrounding tissue. PMID- 11782812 TI - Bioterrorism 2002. PMID- 11782813 TI - Biological and chemical agents: a brief synopsis. AB - The objective of this article is to provide a concise overview of the most likely biological and chemical agents that could be used as biochemical weapons. The diagnosis, pathology, prevention, decontamination, treatment, and disposition of these biological and chemical agents are presented in a tabular format for quick reference purposes. The information provided outlines the bare essentials needed to deal with any emergency or catastrophic event involving these agents. PMID- 11782814 TI - Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid in the presence of Co-administered ciprofloxacin. AB - Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid (INH) in the absence and presence of ciprofloxacin (CP) were investigated in healthy female volunteers. Results obtained indicated an absorption form of interaction between INH and CP. This led to delay in gastric emptying and onset of absorption of INH in the upper part of the gastrointestinal tract, resulting in a corresponding delay in the onset of salivary and urinary excretion of the drugs. There was a 1-hour reduction in the time to attain peak saliva concentration of INH (tmax), an insignificant difference in peak saliva concentration (Cmax), and a significant (P = 0.05) increase in AUC(0-24h) of INH in the presence of CP. Cumulative amount of INH excreted in the urine increased approximately 38% in the presence of CP. The calculated plasma-saliva concentration ratios of INH were reduced in the presence of CP and were slightly lower than the experimental values. This indicates increased amount of the drug secreted into saliva in the presence of CP and possible buccal partitioning of the drug. Overall, results of the current study indicate that CP delayed the onset but not the extent of INH absorption. Therefore, concurrent administration of the two drugs was considered relatively safe, and the absorption interaction that may have occurred may not be of reasonable clinical consequence. PMID- 11782815 TI - Rapid determination of partition coefficients between n-octanol/water for cardiovascular therapies. AB - The lipid solubility of a pharmaceutical may greatly influence its tissue activity. To evaluate lipid solubility of a group of cardiovascular agents a procedure to determine partition coefficients in n-octanol/water for a series of cardiovascular compounds was described. Ultraviolet absorbance measurements were used to assess partitioning between the two liquid phases of these compounds. In this study, sotalol was found to be the most hydrophilic (n-octanol/water ratio of 0.33) and fosinopril-sodium was the most lipophilic (ratio of 6.19). This is a versatile method permitting the evaluation of lipophilicity and, thus, parameters governing the events leading to pharmacologic actions such as gastrointestinal dissolution, absorption, and bioavailability. These observations can be related to a drug series, composed of several compounds having structural similarities or minor variations. The lipid solubility of a compound can markedly alter its side effects profile, especially because lipophilic drugs enter the central nervous system with facility. Additionally, lipophilic agents may enter target tissue with greater ease than nonlipophilic compounds and thus possess local intracellular effects in addition to a macro systemic action. PMID- 11782816 TI - Serum iron, transferrin saturation, ferritin, and dietary data in age-related macular degeneration. AB - Iron (Fe) is a tightly metabolically controlled mineral and growth factor for all living cells. Iron not bound in erythrocyte hemoglobin is transported by the plasma iron transport protein transferrin (Tf) and bound within cells by ferritin. Apo-Tf and apo-hemopexin are also known to be made locally in the retina. Free Fe is cytotoxic, promotes oxidation/lipid peroxidation, has been implicated as a risk factor in cardiac disease, and is itself associated with age related macular degeneration (ARMD), the leading cause of blindness in aging western societies. The authors evaluated Fe overload serum markers and dietary intake in patients with atrophic ARMD. After obtaining informed consent, an Fe panel consisting of serum Fe, total Fe binding capacity (TIBC), and ferritin was performed on 75 veterans (70 men, five women) with an average age of 75 years with a diagnosis of atrophic ARMD by combined criteria of International Retinal Classification and psychophysical/symptom abnormalities. Tf saturation was calculated by dividing serum Fe concentration by TIBC. Dietary iron with and without supplementation and vitamin C intake were determined for 86 patients using the Harvard School of Public Health/Department of Nutrition Food Frequency Questionnaire. Statistically significant correlations (P <0.1) were found between serum and dietary Fe (r = -.26), between serum Fe and serum ferritin (r =.34), and between dietary Fe and dietary vitamin C (r =.30). The data on mostly male geriatric veterans with atrophic ARMD indicate that single time-point assessment of systemic Fe status and dietary Fe is not useful. However, serial multiple-year data, correlating Fe markers with disease, may still be important. Also, because Fe transport proteins do not cross the blood-retina barrier, the local cellular toxic effects of Fe must also be considered. PMID- 11782817 TI - 4-aminopyridine influences heart rate variability in long-standing spinal cord injury. AB - Humans with traumatic spinal myelopathy exhibit intralesional conduction block and autonomic failure as pathophysiologic sequelae of their injury. Analysis of heart rate variability (HRV) provides a means of assessing changes in the function of the autonomic nervous system (ANS) and the cardiac sequelae of injury. Thirteen patients with long-standing spinal cord injury (SCI) and 13 able bodied controls were studied. Each patient received a single 10-mg dose of an immediate release (IR) formulation of 4-aminopyridine (4-AP). Twenty-four hour heart rate (HR) and HRV data were acquired using a Holter ambulatory electrocardiographic (ECG) monitor. Analysis of acquired data was carried out using a minicomputer programmed to separate ECG R-R intervals into frequency patterns that appear as peaks dispersed along a frequency range of 0.0 to 1.0 Hz. Twenty-four hour baseline, pretreatment low-frequency (LF) HRV power was diminished in all patients with SCI compared with able-bodied-controls and was significantly decreased in tetraplegic patients (P = 0.03). This difference in LF HRV power disappeared during the 24 hours immediately after administration of 4 AP, and mean LF HRV power in tetraplegic patients became indistinguishable from LF HRV power in controls. 4-Aminopyridine appears to influence ANS function and LF HRV in humans with long-standing SCI. PMID- 11782818 TI - Interspecies scaling: predicting oral clearance in humans. AB - The objective of this study was to test the interspecies scaling approach for a wide variety of drugs to predict oral clearance in humans from animal data. This study is an attempt to evaluate whether the rule of exponents of Mahmood and Balian for the prediction of systemic clearance can also be applied for the prediction of oral clearance in humans. Three different methods were used to generate log-log plots to scale up the clearance values: (1) clearance versus body weight (simple allometric equation), (2) the product of clearance and maximum life-span potential (MLP) versus body weight, and (3) the product of clearance and brain weight versus body weight. Data from 32 drugs were analyzed, and it was concluded that the oral clearance of drugs could be best predicted using one of the allometric equations. PMID- 11782819 TI - Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. AB - Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2-specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patient's global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients. PMID- 11782821 TI - Crossover studies with continuous variables: power analysis. AB - The crossover design is a sensitive means of determining the efficacy of new drugs because it eliminates between-subject variability. However, if the response in the first period carries on into the second (carryover effect) or if time factors cannot be kept constant in a lengthy crossover (time effects), its statistical power may be jeopardized. This may be equally true if a negative correlation exists between treatment responses. We recently demonstrated that the crossover design with binary variables is a powerful method even if correlation between treatment responses is negative. Power analysis of crossover trials with continuous variables has not been explicitly studied. Using the Scheffe model for the assessment of treatment effect, carryover effect, and time effect, we drew power curves of hypothesized crossover studies with different levels of correlation between drug response. We demonstrate that the sensitivity of testing is largely dependent on the levels of correlation between drug response. When positive, we have a great deal of sensitivity with which to test treatment effect and little sensitivity to test carryover or time effect. When negative, the opposite is observed. The correlation level in a crossover comparison is a major determinant of the sensitivity of testing. Treatments from one class with one mode of action frequently have a positive correlation and should be particularly considered for crossover comparisons. With treatment comparisons of totally different classes of drugs/modes of action, the opposite is true. It is hoped that this work affects the design of future crossover trials. PMID- 11782820 TI - Meperidine: a critical review. AB - Meperidine was initially synthesized as an anticholinergic agent but was soon discovered to have analgesic properties. Although meperidine's anticholinergic effects were demonstrated in vivo, the anticholinergic effects on the biliary and renal tracts have not been demonstrated in vivo. Studies have clearly demonstrated that meperidine is no more efficacious in treating biliary or renal tract spasm than comparative mu opioids. The initial studies demonstrating the analgesic efficacy of meperidine were mostly case reports and not double-blind, randomized, controlled trials in specific populations. Subsequent comparative studies failed to demonstrate any advantages of meperidine over comparable doses of other analgesics. Meperidine was portrayed in practice and teaching as having unique clinical advantages. The analgesic effects of meperidine are not pronounced, and, in addition, meperidine use is complicated by unique side effects including serotonergic crisis and normeperidine toxicity. Meperidine's poor efficacy, toxicity, and multiple drug interactions have resulted in a movement to replace meperidine with more efficacious and less toxic opioid analgesics. PMID- 11782822 TI - Serial electrocardiographic changes as a predictor of cardiovascular toxicity in acute tricyclic antidepressant overdose. AB - Tricyclic antidepressant agents continue to be a leading cause of significant morbidity and mortality in reported poisonings involving pharmaceutical agents. Although the history and physical examination play an important role in the assessment of patients with tricyclic antidepressant overdose, the presence of anticholinergic features on examination cannot predict the severity of the overdose. Several clinical variables, in particular electrocardiographic (ECG) changes, have been proposed as a guide to determine the severity of the tricyclic antidepressant poisoning. The authors describe a patient with tricyclic antidepressant overdose who presented with altered mental status and whose serial ECG changes played a significant role in diagnosing and predicting the impending cardiovascular toxicity. The role of ECG changes in making the diagnosis and assessing the severity of the tricyclic antidepressant overdose is reviewed. PMID- 11782824 TI - Continuous therapeutic ultrasound accelerates repair of contraction-induced skeletal muscle damage in rats. AB - OBJECTIVE: To examine the effect of ultrasonography on the repair of muscle injured through repeated eccentric contractions. DESIGN: Randomized, case-control study. SETTING: Laboratory animal facility. ANIMALS: Thirty-three Sprague-Dawley rats. INTERVENTIONS: Specimens were anesthetized and each foot strapped, in turn, onto a motorized foot pedal, which moved the ankle repeatedly through a range of 110 degrees. Extensor digitorum longus muscles were injured by stimulating the peroneal nerve during foot plantarflexion. Continuous 1.0MHz ultrasound treatments at 0.5W/cm(2) were applied through water submersion technique to 1 limb daily for 3, 5, or 7 days postinjury. The contralateral limb served as an injured control. MAIN OUTCOME MEASURES: Extensor digitorum longus maximum isometric tetanic force (P(o)) was measured in vitro from all extensor digitorum longus muscles and used as a functional index of muscle injury. RESULTS: Analysis of variance and Tukey post hoc analysis showed no significant differences in P(o) between treated and untreated limbs at 3 and 5 days, but at 7 days postinjury, P(o) of ultrasound-treated muscle was significantly higher than was untreated muscle. CONCLUSION: Seven days of continuous therapeutic ultrasound improved force production after contraction-induced muscle injury. PMID- 11782825 TI - Transcutaneous electric nerve stimulation: the effect of intensity on local and distal cutaneous blood flow and skin temperature in healthy subjects. AB - OBJECTIVE: To determine what effect transcutaneous electric nerve stimulation (TENS) intensity has on local and distal cutaneous blood flow and skin temperature. DESIGN: Double-blind conditions. SETTING: University research laboratory. PARTICIPANTS: Forty subjects (20 men, 20 women) randomly assigned to 1 of 4 groups (10 per group): control, above-motor-threshold TENS, below-motor threshold TENS, or perception-threshold TENS. INTERVENTION: TENS (4Hz, 200micros) was applied over the median nerve of the right forearm for 15 minutes. MAIN OUTCOME MEASURES: Blood flow measured by laser Doppler flowmeter and skin temperature measured by skin thermistor were recorded during TENS and for 15 minutes after it. RESULTS: Significant differences occurred between groups for forearm (P <.0001; repeated-measures analysis of variance) but not fingertip cutaneous blood flow. Post hoc Fisher tests showed a significant increase in forearm blood flow during TENS application in the above-motor-threshold TENS group compared with the other 3 groups. No significant differences between groups for skin temperature data were observed. CONCLUSIONS: The effect of TENS on cutaneous blood flow depends on whether muscle activity is induced. Low-frequency TENS applied above the motor threshold significantly increases local cutaneous blood flow. There were no significant differences between groups for skin temperature. PMID- 11782826 TI - The Wheelchair Skills Test: a pilot study of a new outcome measure. AB - OBJECTIVE: To evaluate the practicality, safety, reliability, validity, and usefulness of a new Wheelchair Skills Test (WST). DESIGN: A pilot study with within-subject comparisons. SETTING: Rehabilitation center. PATIENTS: Twenty-four wheelchair users (11 with amputations, 4 with stroke, 3 with musculoskeletal disorders, 3 with spinal cord injury, 3 with neuromuscular disorders). INTERVENTION: The WST. MAIN OUTCOME MEASURES: Subjects were videotaped while performing 33 skills twice (>10d apart). Their ability to perform each skill was rated on a 3-point ordinal scale. The test-retest, intra-, and interrater reliabilities were determined. Each subject's occupational therapist completed a visual analog scale (VAS), reflecting a global rating of the subject's manual wheelchair skills. We assessed validity by evaluating whether the WST detected expected changes (construct validity) and how well the total WST scores correlated with the occupational therapists' global ratings (concurrent validity). Each occupational therapist also used a VAS to quantify the usefulness of the WST. RESULTS: The mean time required to administer the WST was 29 minutes. There were no adverse incidents. For the test-retest, intra-, and interrater reliabilities, the correlations for the total scores were .65 (P =.001), .96 (P <.001), and .95 (P <.001), respectively. The 9 therapists unanimously endorsed 30 (91%) of the 33 WST skills. The correlation between the mean changes in the WST and global rating scores was .45 (P <.05). There was a slight negative relationship between total WST score and age (P <.05). There were no significant differences related to the diagnoses accounting for wheelchair use. Wheelchair users with more than 3 weeks of experience with their wheelchairs scored higher than those with less experience (P =.0085). The correlations between the WST and global rating scores ranged from .40 to .54 (P <.05). Through Rasch analysis, we eliminated 6 skills, with the remaining skills comprising a unidimensional screening test of wheelchair ability. The mean VAS score for perceived usefulness was 59%. CONCLUSIONS: The WST is practical, safe, well tolerated, exhibits good to excellent reliability, excellent content validity, fair construct and concurrent validity, and moderate usefulness. This pilot study makes an important contribution toward meeting the need for a well-validated outcome measure of manual wheelchair ability. PMID- 11782827 TI - Oral creatine supplementation enhances upper extremity work capacity in persons with cervical-level spinal cord injury. AB - OBJECTIVE: To examine the effects of short-term creatine monohydrate supplementation on the upper extremity work capacity of persons with cervical level spinal cord injury (SCI). DESIGN: Randomized, double-blind, placebo controlled, crossover design study. Consists of 2 treatment phases lasting for 7 days, separated by a 21-day washout period. SETTING: University research laboratory trial. PARTICIPANTS: Sixteen men with complete cervical-level SCI (C5 7). INTERVENTION: Subjects were randomly assigned to 1 of 2 groups and received either 20g/d of creatine monohydrate supplement powder or placebo maltodextrin powder for the first treatment phase; the treatment was reversed in the second phase. Incremental peak arm ergometry tests, using 2-minute work stages and 1 minute recovery periods, were performed immediately before and after each treatment phase (total of 4 assessments). The initial stage was performed unloaded, with power output progressively increased 10 watts/stage until subjects had achieved volitional exhaustion. MAIN OUTCOME MEASURES: Peak power output, time to fatigue, heart rate, and metabolic measurements, including oxygen uptake (VO2), minute ventilation, tidal volume (VT), and respiration frequency. RESULTS: Significantly greater values of VO2, VCO2, and VT at peak effort after creatine supplementation (P <.001). CONCLUSIONS: Creatine supplementation enhances the exercise capacity in persons with complete cervical-level SCI and may promote greater exercise training benefits. PMID- 11782828 TI - Mothers with spinal cord injuries: impact on marital, family, and children's adjustment. AB - OBJECTIVE: To evaluate how mothers with spinal cord injury (SCI) adjust to parenting, their marriages, and their families, and how their children adjust to their mothers' disability. DESIGN: Randomized control study of mothers with SCI and their children, matched to able-bodied mothers and their children on key demographic variables. SETTING: Subjects were selected from 7 regional Spinal Cord Injury Model Systems from across the United States. PARTICIPANTS: A total of 310 volunteers (experimental: 88 mothers with SCI, 46 partners, 31 children; matched controls: 84 able-bodied mothers, 33 partners, 28 children). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Children's adjustment, gender role identity; self-esteem; children's attitude toward mother and father; dyadic and family adjustment; parenting stress; and satisfaction. RESULTS: No significant differences were found between mothers with SCI and able-bodied mothers. Moreover, there were no significant differences between children raised in families with mothers with SCI and children raised in families with able bodied mothers. Also, no significant differences were found in dyadic or family functioning with mothers with SCI or able-bodied mothers. CONCLUSIONS: SCI in mothers does not appear to affect their children adversely in terms of individual adjustment, attitudes toward their parents, self-esteem, gender roles, and family functioning. Our results may challenge health care providers, social policy makers, and the general public to end negative stereotyping of children, couples, and families with a disabled mother and wife. PMID- 11782829 TI - Leukocyte subtypes in electroejaculates of spinal cord injured men. AB - OBJECTIVES: To determine the level of leukocytospermia and seminal leukocyte subtypes in men with spinal cord injury (SCI) and to compare the findings with those of fertile, able-bodied controls. DESIGN: Prospective, controlled clinical trial. SETTING: University infertility practice. PARTICIPANTS: Thirteen able bodied fertile men age matched to 17 men with SCI seeking reproductive rehabilitation. INTERVENTIONS: Vibratory stimulation and antegrade electroejaculation for SCI group; manual ejaculation for controls. MAIN OUTCOME MEASURES: Immunoperoxidase technique on a panel of antileukocyte monoclonal antibodies to obtain the leukocyte subpopulations: B cells, T cells, neutrophils, and macrophages. Immunohistochemical staining and scoring to obtain the mean number of leukocytes and spermatozoa per high power field. The ratios of leukocyte to sperm and leukocyte subtype to sperm were tabulated. RESULTS: Total white blood cells, neutrophils, and macrophages in the SCI population were significantly higher than those in the ejaculates of controls. Although not significantly elevated, all the other evaluated subsets were higher in the SCI group then in the controls. CONCLUSIONS: Leukocytospermia appears to be a pervasive abnormality in the semen recovered from men with SCI. The SCI group had significant elevations of total seminal leukocytes after electroejaculation. Compared with controls, men with SCI had significantly more seminal neutrophils and macrophages. Asthenospermia, universally observed in men with SCI, may be attributable, among other causes, to leukocytospermia. PMID- 11782830 TI - Treatment of pressure ulcers by serial casting in patients with severe spasticity of cerebral origin. AB - OBJECTIVE: To assess the effectiveness of serial casting in the treatment of pressure ulcers caused by severe spasticity. DESIGN: Case series. SETTING: A clinic for the rehabilitation of persons with neurologic disorders. PATIENTS: Nine patients with 11 pressure ulcers resulting from severe cerebral spasticity, the ulcers being intractable to conventional management because of repeated friction and/or inaccessibility. INTERVENTION: Serial casting of the limb(s) with the pressure ulcer(s), with either fenestration or a cast arch providing access to the wound. MAIN OUTCOME MEASURES: Improved healing of pressure ulcers, as quantified with the National Pressure Ulcer Advisory Panel classification system. RESULTS: Within a mean of 4.6 weeks, 7 ulcers healed completely and 4 improved markedly. The casting caused no complications. Moreover, extension deficits improved markedly in all patients (105 degrees +/- 27 degrees to 17 degrees +/- 10 degrees ). CONCLUSION: Serial casting may be a valuable tool in the treatment of pressure ulcers at the extremities of patients with severe cerebral spasticity. PMID- 11782831 TI - The relationship between pressure ulcers and skin blood flow response after a local cold provocation. AB - OBJECTIVE: To study the relationship between an impaired blood flow response after a local cold stimulus, testing nerve regulation of the local blood flow response, and an increased risk of developing pressure ulcers. DESIGN: An observational, longitudinal, prospective study. SETTING: Dutch nursing home. PATIENTS: Eighty-two newly admitted somatic nursing home patients, age 60 years and older. INTERVENTION: A local cold stimulus (17 degrees C) applied to the trochanter major. MAIN OUTCOME MEASURES: On admission, blood flow response to a local cold stimulus. As the stimulus was withdrawn, the temperature measured at the skin increased asymptotically toward the final temperature, T(f). The velocity of this rise was characterized by the time constant, tau, of the process. On admission, and weekly during a 4-week follow-up period, the presence or absence of pressure ulcers was verified. RESULTS: The blood flow response time correlated significantly with the risk of developing pressure ulcers. The patients who developed pressure ulcers during the follow-up period had a significantly longer response time than the patients who did not. CONCLUSIONS: Malfunction of the nervous regulatory mechanisms of the local blood flow is partially responsible for an increased susceptibility to pressure ulcer formation. PMID- 11782832 TI - Physical performance tasks: what are the underlying constructs? AB - OBJECTIVES: To investigate the structural validity of a battery of physical performance tasks and to investigate the construct validity of the resulting factors. DESIGN: A measurement study. SETTING: A large, private orthopedic clinic and a physical therapy clinic in an urban area. PARTICIPANTS: One hundred three consecutive adult patients with low back pain who were referred for physical therapy assessment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The physical performance battery was composed of the 50-foot speed walk, 5-minute walk, repeated trunk flexion, sit to stand, loaded reach, rollover tasks, and Sorensen upper-body lift. Participants also completed 5 self-report measures. RESULTS: Two correlated (.74) factors, speed and coordination and endurance and strength, were derived from the physical performance tasks. The Sorenson upper body lift task was the only indicator that was not useful in defining the factors. Both factors had statistically significant correlations with measures of physical disability, lack of self-efficacy, and negative affect. Both factors had a trivial correlation with a numeric rating of pain intensity. CONCLUSIONS: There is support for 2 meaningful empiric groupings (ie, the derived factors) of the performance tasks. Pain intensity had a trivial overlap with speed-coordination and endurance-strength factors. PMID- 11782833 TI - Balance loss when lifting a heavier-than-expected load: effects of lifting technique. AB - OBJECTIVES: To compare the lifting techniques of subjects who did and did not maintain their balance with an unexpectedly heavy load, and to examine whether the balance loss increased low back loading. DESIGN: Repeated-measures design. SETTING: A research laboratory. PARTICIPANTS: Fourteen healthy volunteers were assigned to 2 groups in the post hoc analysis. Group 1 (7 men; mean age, 25.6 +/- 4.2yr; height, 1.78 +/-.08m; weight, 83.0 +/- 8.5kg; lifting capacity, 63.2 +/- 8.0kg) maintained balance and was matched to group 2 (7 men; mean age, 26.3 +/- 4.1yr; height, 1.75 +/-.06m; weight, 78.2 +/- 5.3kg; lifting capacity, 64.7 +/- 4.9kg) who lost balance. INTERVENTIONS: Subjects lifted boxes of 5%, 20%, and 35% of their lifting capacity. Load magnitude was expected or unexpected. MAIN OUTCOME MEASURES: Center of mass (COM), lower body mechanics, ground reaction forces, and angular and horizontal momentum. RESULTS: Group 1 consistently showed greater lumbar flexion, less knee flexion, and a higher COM just before and after load liftoff. During the heavier-than-expected 35% lift, the trunk angular velocities lifts indicated that both groups experienced eccentric trunk extensor muscle contractions. CONCLUSIONS: The semisquat technique may protect against balance loss when lifting unexpectedly heavy loads. Eccentric muscle contractions and rapid increases in lumbar joint reaction moments may increase the risk of low back injury when there is a large, unexpected increase in the weight of the lifted load. PMID- 11782834 TI - Scapular behavior in shoulder impingement syndrome. AB - OBJECTIVE: To quantify the contribution of each scapular rotation to the scapular total range of motion (ROM) in both shoulders of persons with a unilateral shoulder impingement syndrome (SIS), to compare 3-dimensional (3D) scapular attitudes of their symptomatic and asymptomatic shoulders in flexion and in abduction, and to characterize the scapular behavior of these subjects by classifying them into subgroups based on scapular tilting differences between their symptomatic and asymptomatic shoulders. DESIGN: Comparisons of 3D scapular attitudes, scapular total ROM, and percentage of contributions of each scapular rotation to the scapular total ROM. SETTING: A motricity laboratory. PARTICIPANTS: Fifty-one subjects, including 41 with a SIS (29 had an asymptomatic contralateral shoulder) and 10 healthy subjects. INTERVENTIONS: The 3D scapular attitudes were calculated with the subjects in a standardized seated position; with the arm at rest; or at 70 degrees, 90 degrees, and 110 degrees of shoulder flexion and abduction. Axial rotation angles were calculated using a fixed set of Cardanic angles. MAIN OUTCOME MEASURES: At 90 degrees of arm elevation, data from 10 shoulders of healthy subjects were used to set up normative values (99% confidence interval of mean 3D scapular attitudes) to compare with 3D scapular attitudes of symptomatic and asymptomatic shoulders of SIS subjects. We analyzed the scapula behavior of subjects with SIS and classified them into subgroups based on scapular anterior tilting asymmetry. RESULTS: In flexion, almost half of the scapular total ROM was provided by anterior tilting (48.2%-51.3%), whereas in abduction, external rotation (40.3%-42.4%) was the main contributor. Scapular total ROM was higher in abduction than in flexion in all arm positions for both shoulder groups (P <.01). Also, 3D scapular attitude patterns of both shoulders of SIS subjects were different from those of healthy subjects. At 90 degrees, scapular asymmetry in anterior tilting allowed us to classify SIS subjects with respect to more (lead) or less (lag) scapular tilting in the affected side (P <.0001) or no difference (P =.11) between the sides (symmetrical). No significant differences (P >.05), except for a small 2 degrees difference in transverse rotation during arm flexion at 110 degrees (P =.002), were observed in 3D scapular attitudes and scapular total ROM between both shoulders of SIS subjects. Patterns of 3D scapular attitudes and scapular total ROM were significantly different between flexion and abduction arm positions (P <.05). CONCLUSIONS: The contribution of rotations and scapular total ROM differed according to the plane of arm elevation in SIS subjects. Group analyses revealed no differences in 3D scapular attitudes between symptomatic and asymptomatic shoulders of subjects with unilateral SIS. This could be caused by the use, in SIS subjects, of inappropriate neuromuscular strategies affecting both shoulders. However, individual analyses revealed scapular asymmetry in the sagittal plane, which suggests that SIS subjects with less anterior tilting in the symptomatic shoulder, as compared with the asymptomatic contralateral one, may be at high risk of developing chronic SIS. This last finding provides scientific evidence to focus rehabilitation protocols toward a restoration of anterior tilting. PMID- 11782835 TI - Comparative responsiveness of locomotor tests and questionnaires used to follow early recovery after total knee arthroplasty. AB - OBJECTIVES: To compare the responsiveness of 3 locomotor tests and 2 questionnaires in the early stage after a total knee arthroplasty (TKA) and to determine if the 4 responsiveness statistics ranked the measures similarly. DESIGN: Longitudinal study. SETTING: Rehabilitation institute. PARTICIPANTS: Twenty-five men and 40 women with knee osteoarthritis scheduled for a first TKA. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Six-minute gait distance, in-laboratory gait speed and stair ascent duration, Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index difficulty subscale, and Medical Outcomes Study Short-Form 36-Item Health Survey role-physical and physical functioning subscale scores. Effect size, standardized response mean, paired t test, and relative efficiency statistics were computed for 3 time intervals: (1) before TKA to 2 months after TKA, (2) 2 to 4 months after TKA, and (3) before TKA to 4 months after TKA. RESULTS: Responsiveness varied according to tests and intervals considered. For all intervals, the WOMAC difficulty subscale was the most responsive questionnaire and the 6-minute gait test was the most responsive locomotor test. Stair ascent duration was the least responsive measure. Of the responsiveness indices used, only effect size ranked the tests differently. CONCLUSIONS: The 6-minute gait test and the WOMAC difficulty subscale are recommended for outcome assessment during the early recovery period after TKA. Because interpretation guidelines are available and confidence intervals can be calculated for it, the standardized response mean is the most useful statistic. PMID- 11782836 TI - Reflex sympathetic dystrophy of the left hand and motor impairments of the unaffected right hand: impaired central motor processing? AB - OBJECTIVE: To test whether central motor processing can be impaired in chronic reflex sympathetic dystrophy (RSD). DESIGN: Experimental 2-group analysis. SETTING: Tertiary care center in the Netherlands. PARTICIPANTS: Five patients with stage 3 RSD of the left forearm, free of symptoms and complaints in the right forearm; and 10 healthy control subjects. INTERVENTION: On a digitizer, RSD patients and controls had to draw 3 sequences of graphemes of different complexity with their (unaffected) dominant right hand. The drawing tracks were segmented in time periods between points of velocity minima of the pen tip. MAIN OUTCOME MEASURES: Mean velocity, coefficients of variation of both length and movement time per segment, and mean intersegmental pausing time were calculated for each sequence. RESULTS: A repeated-measures analysis of variance by using the multivariate method yielded a 35% lower mean velocity (F(1,13) = 5.83, P =.031), a 110% larger segment length variability (F(1,13) = 9.72, P =.008) and a 60% larger variability of movement time per segment (F(1,13) = 5.78, P =.032) in RSD patients. No group difference was found for intersegmental pausing time or any interaction effect with the type of task. CONCLUSION: Patients with chronic RSD have a normal ability to preprogram sequential movements of their unaffected hand; but with impaired temporospatial coding and movement execution. We concluded that cortical mechanisms may be involved in motor impairments in patients with chronic RSD. PMID- 11782837 TI - Vitamin K deficiency and osteopenia in vitamin D-deficient elderly women with Parkinson's disease. AB - OBJECTIVE: To assess the influence of vitamin K on bone mineral density (BMD) in vitamin-D-deficient women with Parkinson's disease (PD). DESIGN: Cross-sectional study. SETTING: Neurology department at a university medical center in Japan. PARTICIPANTS: Sixty-two women with PD (mean age, 70.7yr) and 62 age-matched controls. Patients were divided into 2 groups according to their functional capabilities: group A (independent: stages I-II of Hoehn and Yahr stages of Parkinson's disease, n = 26); and group B (dependent: Hoehn and Yahr stages 3-5; n = 36). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sera were analyzed to relate vitamin K concentrations to bone-related biochemical indices. BMD was measured by computed radiograph densitometry. RESULTS: Group B had significantly lower metacarpal BMD (P <.0001) lower serum concentrations of vitamin K1 (P <.01) and 25-hydroxyvitamin D (25-OHD; P <.0001) than group A. Serum undercarboxylated osteocalcin levels were higher in group B than in group A (P <.0001). The serum concentration of vitamin K1 correlated positively with that of 25-OHD (r =.735, P <.0001), and negatively with undercarboxylated osteocalcin (r = -.751, P <.0001) and Hoehn and Yahr stages (r =.787, P <.0001). Multiple regression analysis identified Hoehn and Yahr stages, vitamin K1, 25-OHD, and undercarboxylated osteocalcin as independent determinants of BMD (P <.0364.0003). CONCLUSION: In functionally dependent women with PD, nutritional vitamin K1 deficiency is believed to reduce production of fully carboxylated osteocalcin, causing reduced BMD. PMID- 11782838 TI - Evaluating the effectiveness of stroke rehabilitation: choosing a discriminative measure. AB - OBJECTIVE: To evaluate the discriminative ability of several measures of physical disability used to determine quality of outcome for poststroke rehabilitation. DESIGN: A comparative study, using Rasch analysis, of the discriminative ability of functional status and mobility measures in rehabilitation patients with stroke. SETTING: A 26-bed rehabilitation unit, on site of a tertiary teaching hospital in Melbourne, Australia. PARTICIPANTS: A consecutive sample of 106 patients with acute stroke admitted for rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch analysis of the motor subscale of the FIM instrument, Motor Assessment Scale, Functional Ambulation Classification, gait velocity, and gait endurance. RESULTS: The more difficult items of the FIM motor scale adequately discriminated among higher functioning patients. The gait velocity measure further distinguished 9% of the sample, who functioned at a higher level than could be indicated by FIM motor subscale. The other measures did not add levels of discrimination to that provided by the FIM motor. Ability estimates provided by Rasch analysis of the FIM motor scale were a more accurate indication of ability than raw scores. Raw scores underestimated change in ability observed at higher levels of ability. CONCLUSION: Rasch estimates of the FIM motor subscale provide a discriminative measure for evaluating outcomes and change in ability achieved in stroke rehabilitation. PMID- 11782839 TI - Course of functional improvement after stroke, spinal cord injury, and traumatic brain injury. AB - OBJECTIVE: To examine functional improvement patterns of persons with stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). DESIGN: Statistical analysis of data from a multisite study evaluating rehabilitation outcomes. SETTING: Eight inpatient rehabilitation facilities. PARTICIPANTS: A total of 314 consecutive admissions of persons with stroke, SCI, and TBI who received acute medical rehabilitation between 1994 and 1998. INTERVENTION: Calibration of motor and cognitive items from the FIM instrument, grouping of cases by number of weeks of rehabilitation (length of stay [LOS] groups), and plotting of weekly averages across time. MAIN OUTCOME MEASURES: Weekly motor and cognitive functional status. RESULTS: With the exception of cognitive functioning for persons with SCI, LOS was related to initial functional status, with patients with greater disability having longer LOS (eg, initial motor status for persons with stroke was 48.3 for those with a 2-week stay, 36.8 for a 6-week stay, with the averages between decreasing monotonically). With the exception of cognitive gains for person with TBIs, the amount of functional gain during rehabilitation was essentially the same for all LOS groups (eg, the overall average total motor gain for persons with SCI is 22.3, with no patterns of increase or decrease across LOS groups); however, the rate of improvement in motor (but not cognitive) functioning differed across LOS groups, with patients with shorter stays having the greater rates of improvement (eg, the overall average weekly motor gain for persons with SCI was 3.6, with the averages by LOS group monotonically decreasing from 6.4 for those with 4-week stays to 2.7 for those with 9-week stays). CONCLUSIONS: When examined separately for persons grouped by LOS, functional status improved linearly during the rehabilitation stay, with differences in rate of improvement depending on initial functional status. PMID- 11782840 TI - Return to productive activity after traumatic brain injury: relationship with measures of disability, handicap, and community integration. AB - OBJECTIVES: To identify which factors are associated with successful return to productive activity (RTPA) 1 year after hospitalization with traumatic brain injury (TBI) and to examine the relations between successful RTPA and other measures of impairment, disability, handicap, and integration into the community. DESIGN: Prospective study with 1-year follow-up. SETTING: Level I trauma center. PARTICIPANTS: One hundred five respondents from a cohort of 378 adults hospitalized with TBI admitted between September 1997 and May 1998. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Return to productive work 1 year after injury; Disability Rating Scale (DRS); and Community Integration Scale (CIQ). RESULTS: Of the 105 participants, 72% achieved RTPA. Logistic regression showed an association between RPTA and the following factors: premorbid educational level, premorbid psychiatric history, violent mechanism of injury, discharge status after acute hospitalization, prior alcohol and drug use, and injury severity. Handicap and community integration at 1-year postinjury, as measured by subscales of the DRS and the CIQ, were also associated with RTPA. CONCLUSION: Premorbid and injury-related variables and measures of handicap and community integration were associated with RTPA at 1 year. To understand and effectively support vocational pursuits in the TBI population, future studies are needed to define further causality and origin of these relationships. PMID- 11782841 TI - The effects of proprioceptive stimulation on cognitive processes in patients after traumatic brain injury. AB - OBJECTIVE: To investigate the hypothesis that proprioceptive stimulation may be effective in the treatment of brain injury, using neurophysiologic and neuropsychologic measures. DESIGN: Cohort analytic study. SETTING: Patients recovering from traumatic brain injury (TBI) in a neurologic rehabilitation hospital were examined. PARTICIPANTS: Eleven patients with TBI (Glasgow Coma Scale score > 3) and 11 healthy control subjects matched for age and education. INTERVENTIONS: Subjects were examined with the event-related potential (ERP) technique during a computerized choice-reaction-time task, in which they had to discriminate between even and odd digits. There were experimental runs with and without vibratory stimuli applied to the left forearm serving as proprioceptive stimulation. In addition, ERPs were recorded to vibratory stimuli without any additional task. MAIN OUTCOME MEASURES: Outcome measures included latencies and amplitudes of the P300 ERP component and of the late negative component. RESULTS: In the passive vibration condition, both groups showed the same ERP distribution. In the choice-reaction-time task, latencies and amplitudes of the P300 differed between the 2 groups. The patient group showed longer P300 latencies, which were shortened by vibratory stimuli. In contrast, the control subjects were not affected by vibratory stimuli. CONCLUSION: Our findings support the hypothesis that pathologic cognitive processes after TBI can be improved by proprioceptive stimulation. Muscle vibration has positive effects on pathologically slowed cognitive processes but not in healthy subjects. PMID- 11782842 TI - Bone density in competitive figure skaters. AB - OBJECTIVES: To compare the bone mineral density (BMD) of competitive female teenage figure skaters with a history of fracture with the BMD of skaters without fracture and to compare each group to age-matched, nonathletic controls. DESIGN: Retrospective age-matched cohort. SETTING: Tertiary care medical center and 3 local skating clubs. PARTICIPANTS: Thirty-six adolescent female competitive skaters (10 with fracture, 26 without fracture) to 22 age-matched controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD was estimated by quantitative ultrasound. RESULTS: Skaters who had suffered stress fractures had BMD values comparable with those of healthy nonathletic controls. However, skaters who had not suffered stress fractures had calcaneal BMD values 15% to 24% greater than either the controls or skaters with fractures. Among the skaters without fracture, there was a 14% to 19% higher calcaneal BMD in skaters who executed triple jumps relative to skaters who performed only double jumps. Furthermore, there was 7% to 11% greater BMD in the landing foot of the skaters relative to the takeoff foot. CONCLUSIONS: Stress fractures in adolescent skaters are not caused by low bone mass but may result from excessive forces placed on a normal skeleton. Our findings also support the hypothesis that higher peak forces are applied to the landing foot relative to the takeoff foot. PMID- 11782843 TI - Antimicrobial prophylaxis for urinary tract infection in persons with spinal cord dysfunction. AB - OBJECTIVE: To assess the benefits and harms of antimicrobial prophylaxis to prevent urinary tract infections (UTIs) in persons with neurogenic bladders caused by spinal cord dysfunction. DATA SOURCES: A broad search strategy with no language restriction was conducted of MEDLINE (1966-January 1998), EMBASE (1974 January 1998), and CINAHL (1982-July 1998) using the general search terms urinary tract, urinary tract infections, bacteriuria, paraplegia, quadriplegia, spinal cord injuries, multiple sclerosis, neurogenic bladder, and neuropathic bladder. Additional articles were identified by experts and by reviewing reference lists of articles obtained from searches. STUDY SELECTION: Criteria included human studies of adults and adolescents who had neurogenic bladder due to spinal cord dysfunction; the studies had to address antimicrobial prophylaxis of UTI and include bacteriuria or UTI as an outcome. We excluded any study that was clearly not a controlled trial or that only included children under the age of 13 years. Two reviewers independently abstracted data, and disagreements were resolved by consensus. DATA EXTRACTION: Two reviewers independently abstracted data, and disagreements were resolved by consensus. Studies were graded by 1 project investigator according to quality criteria developed by Jadad and Schulz. DATA SYNTHESIS: The sizes of the effect of antimicrobial prophylaxis on weekly infection rates from 15 trials that met the inclusion criteria were pooled by using a random effects model. Antimicrobial prophylaxis did not significantly decrease symptomatic infections. Prophylaxis was associated with a reduction in asymptomatic bacteriuria among acute patients (<90d after spinal cord injury; P <.05); 1 patient would require 3.7 weeks of treatment on average to prevent 1 asymptomatic infection. For nonacute patients, the reduction approached statistical significance (P =.06). Prophylaxis resulted in an approximately twofold increase in antimicrobial-resistant bacteria. CONCLUSIONS: The regular use of antimicrobial prophylaxis for most patients who have neurogenic bladder caused by spinal cord dysfunction is not supported. A clinically important effect, however, has not been excluded. Future research should focus on randomized trials in those patients who have recurrent UTIs that limit their daily functioning and well-being. PMID- 11782844 TI - Alendronate increases bone density in chronic spinal cord injury: a case report. AB - Over the first 6 to 16 months after spinal cord injury (SCI), up to a third of bone mass may be lost because of demineralization, resulting in an increased risk for fractures. Studies in postmenopausal women have shown the efficacy of oral alendronate, an aminobisphosphonate, in increasing bone mass. However, the efficacy of alendronate in reversing bone density loss has not been shown in patients with chronic SCI. This article reports on the efficacy of alendronate in increasing bone mass in a patient with neurologically incomplete American Spinal Injury Association class D SCI and Brown-Sequard's syndrome. Bone mass change over 2 years while taking alendronate is compared for a weak extremity (majority of muscles grade 2/5) and strong extremity (majority of muscles grade 4/5) and spine. There was a greater increase in bone mineral density in the weaker lower extremity compared with the stronger one; the spine had the greatest increase overall. PMID- 11782845 TI - Subjective hearing loss and history of traumatic brain injury exhibits abnormal brainstem auditory evoked response: a case report. AB - A 30-year-old woman presented with long-standing subjective unilateral auditory difficulties 13 years after sustaining closed head trauma. The battery of audiologic tests indicated normal hearing, but brainstem auditory evoked response (BAER) tests revealed abnormal neurogenic potentials in the symptomatic ear. The discrepancy between a normal pure tone audiogram and abnormal BAERs suggests that a site of neurologic injury could be causing the patient's problem with auditory perception. Imaging studies with gadolinium enhancement, however, did not document any abnormalities in the brainstem. Our present findings and previously published literature help identify the specific site of a neurologic deficit when routine audiologic tests and imaging studies detect no significant abnormality. PMID- 11782846 TI - Therapeutic uses of magnets. PMID- 11782849 TI - Looking back and looking forward. PMID- 11782850 TI - Quality of care and hospital readmission in congestive heart failure: an explicit review process. AB - BACKGROUND: The effect of hospital quality of care on hospital readmission for patients with congestive heart failure (CHF) has not been widely studied. METHODS AND RESULTS: We examined the effects of clinical factors, hospital quality of care, and cardiologist involvement on 3-month readmission rates in patients with CHF by using a 125-item explicit review instrument comprising 3 major domains: admission work-up, evaluation and treatment, and readiness for discharge. During the 3 months after discharge, 59 (30%) of 205 patients were readmitted for CHF. The average evaluation and treatment score was lower for readmitted patients (63% v 58%; P = .04). The specific quality criteria differing between patients readmitted or not readmitted included the performance of any diagnostic evaluation, performance of echocardiography in patients with unknown ejection fraction or suspected valvular disease, and therapy with an angiotensin converting enzyme inhibitor on discharge. Patients with or = 7.0 mmol/L had already been found in 7 women, 17 participants were diagnosed on that occasion as having new diabetes, 38 had impaired fasting glucose (IFG), and the remaining 248 presented normal fasting glucose values (NFG). Diabetic women showed a worse cardiovascular risk profile, with higher values of triglycerides, body mass index, and diastolic blood pressure than either normoglycemic or IFG subjects. The frequency of atherosclerotic plaques (IMT > 1.2 mm) increased as glucose homeostasis worsened. In multivariate logistic regression analyses, only diabetes mellitus was associated with a significantly increased risk of carotid atherosclerosis (odds ratio [OR], 11.5; 95% confidence interval [CI], 1.4 to 92.7). Our findings suggest a definite association between diabetes mellitus, as defined by the new ADA diagnostic criteria and early carotid structural changes. Furthermore, the condition of IFG does not seem to identify subjects at significantly increased atherosclerotic risk. PMID- 11782873 TI - Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man. AB - In the liver, paracrine interaction between Kupffer cells and hepatocytes influences glucose metabolism. In vitro in rats, nitric oxide (NO), a paracrine mediator, inhibits several pathways of hepatic glucose production. The role of NO on glucose production has not been studied in vivo in humans. Glucose production was measured during N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA) infusion, an inhibitor of NO synthesis in vivo, in 6 healthy men fasting 23 hours in a saline-controlled crossover study. During L-NMMA infusion, NO output decreased 40% to 50%, peripheral vascular resistance increased approximately 22%, and cardiac output (CO) decreased approximately 14%. The decrease in glucose production was not different between L-NMMA and saline. Glucose concentration, substrate supply, and glucoregulatory hormone concentrations were not different; epinephrine was lower with L-NMMA. A 40% to 50% inhibition of NO synthesis in vivo in humans does not affect glucose production during short-term fasting. The hypothesis that NO is an important modulator of basal glucose production in healthy humans in vivo should therefore be rejected. PMID- 11782874 TI - The stimulation of tumor necrosis factor and inhibition of glucose transport and lipoprotein lipase in adipose cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is found throughout the environment in industrialized countries, and most people have had some exposure. TCDD has very high lipid solubility and is concentrated in adipose tissue. Because an epidemiologic association between TCDD exposure and diabetes has been described, we examined the effects of TCDD in adipocytes. The addition of TCDD to 3T3-F442a cells, both at the initiation of differentiation and after cells were fully differentiated, resulted in a 2-fold increase in the secretion of tumor necrosis factor (TNF). When added during differentiation, there was also a 25% decrease in lipid accumulation. In addition to the stimulation of TNF, TCDD affected glucose transport and lipoprotein lipase (LPL) activity. When added to cultures of cells that were undergoing differentiation, TCDD inhibited total 2-deoxyglucose transport in a dose-dependent fashion, with 50% inhibition of glucose transport when added to cultures for 48 hours at 5 nmol/L TCDD. In addition, when cells were exposed to 50 nmol/L TCDD for 48 hours, there was a 40% reduction in LPL activity. Thus, the addition of TCDD to adipocyte cultures resulted in an increase in TNF secretion and a decrease in glucose transport and LPL activity. Because TCDD is concentrated in adipose tissue, these studies provide a possible physiologic mechanism for epidemiologic studies that link dioxin to diabetes. PMID- 11782875 TI - Appendicular lean tissue mass and the prevalence of sarcopenia among healthy women. AB - Studies indicate that deficient skeletal muscle mass or sarcopenia is a major cause of disability and morbidity among the elderly. In part, due to the lack of generally applicable normal values, there is still insufficient epidemiologic data available on the frequency and severity of sarcopenia in health and under various disease-related conditions. The objectives of the present study were to (1) characterize the age- and menopause-related variations in appendicular lean tissue mass (LTM(A)), (2) provide young-normal means and estimate the age specific prevalence of sarcopenia among healthy women. A total of 754 healthy women were included in the study of cross-sectional design. LTM(A) was estimated by dual-energy x-ray absorptiometry (DEXA). Physical characteristics and menopausal status were also registered. LTM(A) as well as height showed significant negative correlation with age with Pearson's r values of -0.43 and 0.06, respectively (P <.05). Trend of finding lower mean values with advancing age remained even when LTM(A) was adjusted for height(2) (ht(2)). Menopause did not seem to have any influence on LTM(A). Young-normal means were obtained from 216 premenopausal women aged 18 to 39 years. Prevalence rates of sarcopenia in healthy women were determined with reference to a cut-off line corresponding to LTM(A) or LTM(A)/ht(2) less than young-normal mean 2 SD and were found to be 40.2% and 12.3%, respectively, among the healthy elderly (>70 years of age). Results of the present study provide further evidence that sarcopenia exists even among otherwise healthy women with increasing age-specific prevalence. Further studies are needed (1) to estimate the prevalence of sarcopenia under various health and disease-related conditions with reference to the hereby given cut-off values and (2) to find therapeutic strategies with beneficial effects in conserving skeletal muscle mass. PMID- 11782876 TI - Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity. AB - Intercellular adhesion molecule-1 (ICAM-1) is 1 of the possible factors linking obesity and diabetes with cardiovascular disease, however, the mechanism of the increase in ICAM-1 concentration in obesity remains unclear. Therefore, the aim of the present study was to assess plasma soluble ICAM-1 (sICAM-1) levels in obese subjects with normal glucose tolerance and to evaluate whether those levels may be related to insulin resistance and tumor necrosis factor-alpha (TNFalpha) system activity. The study was performed in 8 lean and 15 obese subjects. Anthropometric and biochemical parameters were measured, and insulin sensitivity was evaluated using the euglycemic hyperinsulinemic clamp technique (insulin infusion, 50 mU x kg(-1) x h(-1)). Obese subjects were markedly more hyperinsulinemic and insulin resistant and had higher plasma soluble TNF receptor 2 (sTNFR2) and sICAM-1 levels. sICAM-1 was related positively to body mass index (BMI), waist-to-hip ratio (WHR), percent of body fat, glycated hemoglobin (HbA(1c)), plasma insulin and triglycerides (TG), TNFalpha, and sTNFR2 and negatively to insulin sensitivity. Multiple regression analysis showed that only sTNFR2 and insulin sensitivity were independent predictors of sICAM-1 concentrations and were responsible for 66% of sICAM-1 variability. We conclude that an increase in plasma sICAM-1 concentration in obesity is related to TNFalpha system activation and insulin resistance. PMID- 11782877 TI - The cytoskeleton and the regulation of gluconeogenesis: a hypothesis. AB - Previous data from our laboratory indicated a role for the cytoskeleton in the hormonal stimulation of gluconeogenesis. To gain further insight into the role of the cytoskeleton in the regulation of gluconeogenesis, we performed further experiments to examine the possibility that the cytoskeleton is involved in the glucagon-mediated changes in calcium distribution. Perfused livers or isolated liver cells were pretreated with either cytochalasin B or colchicine, agents that disrupt microfilaments and microtubules, respectively. Pretreatment with either agent significantly decreased the glucagon-evoked efflux of labeled calcium. Pretreatment with colchicine was more effective in blocking the influx of calcium into the cells than pretreatment with cytochalasin B. These drugs also prevented the characteristic increase in O(2) uptake, which is usually observed after glucagon administration. Thus, an intact cytoskeleton seems to be a prerequisite for the glucagon-evoked changes in calcium distribution to occur. These changes in calcium fluxes were shown previously to be an essential link in the chain of events leading to the metabolic effects of glucagon. Based on these results and on data obtained by others, a hypothesis is presented here. The hypothesis presumes that the cytoskeleton plays a crucial role in the regulation of gluconeogenesis. The hypothesis further assumes that the cytoskeleton influences gluconeogenesis in 3 ways: (1) by influencing the process of calcium signaling; (2) by changing the rate of enzymatic reactions through association and dissociation of enzymes with the cytoskeleton; and (3) by altering the position of intracellular organelles and the movements of molecules. Each of these points is discussed separately. It is known that the intracellular environment exists as a dense mesh in dynamic motion. According to our hypothesis, hormonal stimulation changes this environment by affecting the ionic composition in the cytosol and the structure of the cytoskeleton. Motion and conformational changes by the cytoskeleton play crucial regulatory functions, influencing metabolic processes. PMID- 11782878 TI - Improved bone biomechanical properties in xylitol-fed aged rats. AB - Our previous studies have shown that dietary xylitol protects against weakening of bone biomechanical properties in experimental postmenopausal osteoporosis. To study whether xylitol preserves bone biomechanics also during aging, a long-term experimental study was performed with rats. Twenty-four male Sprague-Dawley rats were divided into 2 groups. The rats in the control group (NON-XYL group) were fed a basal rat and mouse no. 1 maintenance (RM1) diet, while the rats in the experimental group (XYL group) were continuously fed the same diet supplemented with 10% xylitol (wt/wt). The rats were killed after 20 months. Their femurs were prepared for biomechanical analyses and scanning analyses with peripheral quantitative computed tomography (pQCT). In 3-point bending of the femoral diaphysis, maximum load, maximum elastic load, stiffness, energy absorption, elastic energy absorption, ultimate stress, and yield stress were significantly greater in the XYL group than in the NON-XYL group. This indicates a xylitol induced improvement of both structural and material strength properties of cortical bone. Accordingly, the maximum load of femoral neck was significantly greater in the XYL group. In the pQCT analysis of femoral diaphysis, cortical bone area, cortical thickness (CtTh) periosteal circumference, and cross sectional moment of inertia were greater in the XYL group. The endosteal circumference was smaller in the XYL group. In the pQCT analysis of the femoral neck cortical area of the midneck was significantly greater in the XYL group. This data indicates that xylitol exerted beneficial effects on the cross sectional architecture of the bones. In conclusion, continuous moderate dietary xylitol supplementation leads to improved bone biomechanical properties in aged rats concerning both bone structural and material strength properties. PMID- 11782879 TI - Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo. AB - Alcohol can be considered as a nutritional toxin when ingested in excess amounts and leads to skeletal muscle myopathy. We hypothesized that altered protease activities contribute to this phenomenon, and that differential effects on protease activities may occur when: (1) rats at different stages in their development are administered alcohol in vivo; (2) acute ethanol treatment is superimposed on chronic alcohol-feeding in vivo; and (3) muscles are exposed to alcohol and acetaldehyde in vivo and in vitro. In acute studies, rats weighing approximately 0.1 kg (designated immature) or approximately 0.25 kg (designated mature) body weight (BW) were dosed acutely with alcohol (75 mmol/kg BW; intraperitoneal [IP], 2.5 hours prior to killing) or identically treated with 0.15 mol/L NaCl as controls. In chronic studies, rats (approximately 0.1 kg BW) were fed between 1 to 6 weeks, with 35% of dietary energy as ethanol, controls were identically treated with isocaloric glucose. Other studies included administration of cyanamide (aldehyde dehydrogenase inhibitor) in vivo or addition of alcohol and acetaldehyde to muscle preparations in vitro. At the end of the treatments, cytoplasmic (alanyl-, arginyl-, leucyl-, prolyl-, tripeptidyl aminopeptidase and dipeptidyl aminopeptidase IV), lysosomal (cathepsins B, D, H, and L, dipeptidyl aminopeptidase I and II), proteasomal (chymotrypsin-, trypsin like, and peptidylglutamyl peptide hydrolase activities) and Ca(2+)-activated (micro- and milli-calpain and calpastatin) activities were assayed. (1) Acute alcohol dosage in mature rats reduced the activities of alanyl-, arginyl- and leucyl aminopeptidase (cytoplasmic), dipeptidyl aminopeptidase II (lysosomal), and the chymotrypsin- and trypsin-like activities (proteosomal). No significant effects were observed in similarly treated immature rats. (2) Alcohol feeding in immature rats did not alter the activities of any of the enzymes assayed at 6 weeks. (3) In immature rats, activities of cathepsins B and D were not overtly affected at either 3, 7, 14, 28, or 42 days. (4) Superimposing acute (2.5 hours) on chronic (4 weeks feeding of immature rats) ethanol treatment (ie, chronic + acute) reduced the activities of cytoplasmic proline aminopeptidase and the chymotrypsin- and trypsin-like activities of the proteasome. (5) Cathepsin D activities were reduced in muscle homogenates upon addition of alcohol and acetaldehyde in vitro. (6) Cyanamide pretreatment in combination with alcohol dosage in immature rats did not significantly alter any protease activities. The data suggests that mature rats are more sensitive to the effects of acute alcohol on muscle proteases. Protease activities may be affected by acetaldehyde or alcohol levels as indicated by in vitro experiments. The reduction in muscle protease activities in chronic + acute alcohol superimposition may reflect the effect of acute alcohol dosage alone. Overall, there was no evidence for increased protease activity in any of the experimental situations. PMID- 11782880 TI - Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers. AB - Changes in thyroid function are often described in elderly subjects; however, their pathophysiologic significance and the possible contributory role of both malnutrition and nonthyroidal illness are still debated. The aim of this cross sectional study was to investigate thyroid function in relationship to some markers of the nutritional status in a group of healthy old subjects and in some centenarians living in nursing homes. Patients included 24 clinically healthy elderly women (age, 71 to 93 years), 24 clinically healthy centenarian women (age, 100 to 106 years), and 20 healthy young subjects (age, 22 to 33 years). Blood samples were drawn from each subject for the evaluation of thyroid stimulating hormone (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4),) reverseT(3) (rT3), autoantibodies against thyroglobulin (AbTg) and against thyroid peroxidase (AbTPO), and for the main humoral nutritional markers. TSH and thyroid hormones were assayed by fluoroimmunometric method; rT3 and thyroid autoantibodies by radioimmunoassay (RIA) and enzyme chemiluminescent immunometric assay, respectively. The mean values of TSH, FT(3) and FT(4) fell within the normal range in both groups. However, by comparison to old controls, in centenarian subjects, TSH levels were significantly lower, whereas rT(3) concentrations were slightly, but significantly, increased. Autoantibodies positivity was found in 4.16% of centenarians and in 10.4% and 13.6% of old and young controls. Thus, the incidence of thyroid autoantibodies was lower in centenarians than in old controls. Except for transferrin, lower than the normal range in centenarians, all of the other nutritional markers evaluated fell within the laboratory range of normality. Total cholesterol levels were significantly reduced in centenarians by comparison to old controls. Our results showed an age related decline of the TSH levels and a significant increase of the rT(3) concentrations in centenarians by comparison to old controls. These findings may be related to an age-dependent reduction of the 5'-deiodinase activity rather than to important changes of nutritional markers. PMID- 11782881 TI - The antilipolytic agent 3,5-dimethylpyrazole inhibits insulin release in response to both nutrient secretagogues and cyclic adenosine monophosphate agonists in isolated rat islets. AB - This study intended to test the hypothesis that intracellular lipolysis in the pancreatic beta cells is implicated in the regulation of insulin secretion stimulated by nutrient secretagogues or cyclic adenosine monophosphate (cAMP) agonists. Indeed, although lipid signaling molecules were repeatedly reported to influence beta-cell function, the contribution of intracellular triglycerides to the generation of these molecules has remained elusive. Thus, we have studied insulin secretion of isolated rat pancreatic islets in response to various secretagogues in the presence or absence of 3,5-dimethylpyrazole (DMP), a water soluble and highly effective antilipolytic agent, as previously shown in vivo. In vitro exposure of islets to DMP resulted in an inhibition (by approximately 50%) of the insulin release stimulated not only by high glucose, but also by another nutrient secretagogue, 2-ketoisocaproate, as well as the cAMP agonists 3-isobutyl 1-methylxanthine and glucagon. The inhibitory effect of DMP, which was not due to alteration of islet glucose oxidation, could be reversed upon addition of sn-1,2 dioctanoylglycerol, a synthetic diglyceride, which activates protein kinase C. The results provide direct pharmacologic evidence supporting the concept that endogenous beta-cell lipolysis plays an important role in the generation of lipid signaling molecules involved in the control of insulin secretion in response to both fuel stimuli and cAMP agonists. PMID- 11782882 TI - Relative contribution of insulin sensitivity and beta-cell function to plasma glucose and insulin concentrations during the oral glucose tolerance test. AB - Plasma glucose and insulin concentrations have been used in genetic studies as quantitative phenotypic traits and also as surrogates for insulin sensitivity and beta-cell function. However, the significance of these traits in relation to insulin sensitivity and beta-cell function was unknown. We examined how insulin sensitivity and beta-cell function affected plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). This is a cross sectional study enrolling 105 glucose-tolerant subjects (64 females; age, 18 to 40 years; body mass index, 17.58 to 37.57 kg/m(2); waist-to-hip ratio, 0.649 to 1.033 cm/cm). They participated in both OGTTs and hyperglycemic clamps. The relationship between plasma glucose and insulin concentrations and indices of insulin sensitivity and beta-cell function was examined. Univariate analyses showed that insulin sensitivity index (ISI) had some influence on plasma insulin concentrations (r(2) =.2623 to.3814) during the OGTT; however, it had only modest impacts on plasma glucose levels at 60, 90, and 120 minutes (r(2) =.0537 to.1300). Neither first phase (1stIR) nor second phase insulin response (2ndIR) affected plasma glucose concentrations. Multivariate analyses showed an independent impact (all P <.0001) of ISI on plasma glucose concentrations at 60, 90, and 120 minutes and on plasma insulin concentrations at every time point except at 30 minutes. Except for plasma insulin concentration at 30 minutes, of which 24% of the variation can be explained by 1stIR, beta-cell function (either 1stIR or 2ndIR) only had a very modest impact on 30-, 60-, 90- and 120-minute plasma glucose concentrations and on plasma insulin concentration at 60 minutes. In glucose-tolerant subjects, ISI plays an important role in determining postchallenged plasma glucose concentrations at 60, 90, and 120 minutes, as well as plasma insulin concentrations at fasting, 60, 90, and 120 minutes. However, beta-cell function is only reflected in plasma insulin concentration at 30 minutes through 1stIR. Therefore, we conclude that it is essential to measure beta-cell function in vivo if one plans to study the genetic influence of beta cell dysfunction. PMID- 11782883 TI - Glucokinase gene transfer to skeletal muscle of diabetic Zucker fatty rats improves insulin-sensitive glucose uptake. AB - Skeletal muscle has a prime role in glucose homeostasis. We have previously demonstrated that adenovirus-mediated glucokinase (GK) gene transfer to skeletal muscle of Wistar rats enhances muscle glucose uptake and whole body glucose disposal under conditions of hyperglycemia and hyperinsulinemia. In this study, we have tested whether GK gene transfer to the muscle of the Zucker Diabetic Fatty rat (ZDF), a genetic model of obesity and type 2 diabetes, could improve glycemic control and prevent the onset of hyperglycemia in obese males. We show that GK delivery results in a doubling of total gastrocnemius muscle glucose phosphorylating activity 9 weeks after gene transfer. GK-treated rats exhibited slightly reduced weight and normal insulin-sensitive glucose uptake, as assessed during an insulin tolerance test, whereas age-matched rats treated with a control virus were clearly insulin resistant. The improved glucose uptake in GK expressing rats was associated with higher gastrocnemius lactate content, whereas glycogen and triacylglyceride (TAG) levels were unmodified. Remarkably, GK treated rats showed increased expression of both hexokinase II (HKII) and GLUT4, in accordance with a glucose-dependent regulation of these proteins. Thus, our data show that delivery of GK, despite improving insulin-sensitive glucose disposal in muscle, is not sufficient to prevent or delay the appearance of elevated glucose and insulin levels associated with severe obesity in male ZDF animals. PMID- 11782885 TI - Seminars in Clinical Neuropsychiatry. Introduction. PMID- 11782884 TI - Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. AB - The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach. PMID- 11782886 TI - Assessment and measurement in neuropsychiatry: a conceptual history. AB - Since the time the parent discipline of psychiatry became organized as a profession, one of its ludi saeculares (neuropsychiatry) has enjoyed at least 4 vogues. On each, neuropsychiatry has been known to ally itself to a cause: currently it is the big business of neurobiology. This move can be seen as scientific progress or as a side-effect of the (professional rather than scientific) infighting that affected neuromedicine during the late 19(th) century and which led to the construction of the notion of "neurological disease." Alienists responded to this variously: some, like Kahlbaum and Kraepelin accepted the split and returned to the more botanico approach; others, like Ziehen chose psychology; yet others, like Freud, delved in hermeneutics; lastly, there were those, like Meynert, Wernicke, Von Monakow, and Liepmann who sought an accommodation with neurology. Born out of this compromise, neuropsychiatry has remained a blurred activity (whose definitions range from "psychiatry of neurology" to a crusade for the "naturalization of the mind"). Neuropsychiatric assessment is a methodology designed to collect information about patients whose mental symptoms are thought to be caused by brain disease. When it first appeared, it was torn by the debate between "nomothetic versus idiographic" science. For a time, the neuropsychiatry assessment techniques stuck to the old personalized narratives characteristic of 19(th) century "casenotes" (trying to meet its descriptive, explanatory, therapeutic, legal, and ethical obligations). But during the late 19(th) century, measurement and quantification became part of the new rhetoric of science. Soon enough this affected psychology in general and neuropsychology in particular and neuropsychiatric assessment followed suit. It has changed little since except that now and again old tests and markers are replaced by more "reliable" ones and phenomenological data are squeezed out further. Its laudable enthusiasm for objectivity and truth was ab initio justified by 19(th) century Positivism; currently, it seems to be supported by a naive version of Popperian falsificationism. In the meantime, the scientific worth of the neuropsychiatric assessment remains unclear; indeed, in an age of evidence-based medicine, it is surprising that both its informational and communicational value and its efficiency as a general epistemic tool have not been subjected to any serious empirical testing. PMID- 11782887 TI - Clinical presentations in neuropsychiatry. AB - In this report, the special clinical presentations found in neuropsychiatry are discussed. The point is made that conventional diagnostic schedules such as DSM IV do not serve neuropsychiatry well, and have contributed to a failure to view neuropsychiatry as an independent specialist discipline. In this review some of the characteristic neuropsychiatric syndromes seen in epilepsy, movement disorders, demyelinating, and cerebrovascular diseases are described, followed by a brief discussion of conversion disorder. A plea is made that any future diagnostic schedules contain references to neuropsychiatric disorders and presentations. PMID- 11782888 TI - Physical and neurologic examinations in neuropsychiatry. AB - The direct physical examination of psychiatric patients is underutilized by clinicians and underinvestigated by researchers. Both clinicians and researchers thus bypass important information. The authors review the literature on physical and neurologic examinations, with attention to aspects of these examinations that might specifically enhance the understanding of the psychiatric patient. Coverage includes the "minor" physical anomalies and "soft" neurologic signs. Findings related to the psychiatric conditions themselves are given precedence over findings of general medical importance. Some of the available physical and neurologic examination schedules are reviewed. A unified examination protocol is presented, incorporating physical and neurologic examinations pertinent to both general medical and specifically psychiatric assessment. PMID- 11782889 TI - Electrophysiological assessment of neuropsychiatric disorders. AB - In this article the clinical usefulness and limitations of the routine electroencephalogram (EEG) are discussed. Emphasis is placed on 3 specific clinical situations where EEG can be most useful: the differential diagnosis of dementia versus pseudodementia, the evaluation of episodic behavior disorders including aggressive episodes, and acute confusional states. An atypical clinical presentation is emphasized as the most important indiction for obtaining an EEG evaluation. The issue of controversial EEG waveforms is discussed in some detail. The need for well-designed, controlled studies to further examine these EEG patterns is emphasized. Finally, the limitations of the routine EEG are discussed. The article concludes with a brief mention of the future promise of other electrophysiological testing modalities such as quantified EEG, evoked potentials, and sleep studies. PMID- 11782890 TI - Neuroimaging in neuropsychiatry. AB - Advances in physics, computing, and signal processing have provided a range of computerized brain imaging technologies that facilitate examination of the brain as a dynamical system. This article provides a review of brain imaging advances and their application in neuropsychiatry. The review encompasses (1) a description of the imaging technologies used in neuropsychiatry; (2) an outline of their temporospatial complementarity; (3) application to clinical applications; and (4) suggested future directions including an "integrative neuroscience" approach to neuropsychiatry (in which theoretical models, data and information concerning mechanisms are integrated). In the absence of a unified theory of the brain, an integrated approach is presented as one means of exploring converging brain-imaging evidence in relation to neuropsychiatric disorders. PMID- 11782891 TI - The three cognitive examinations. AB - Cognitive dysfunction is a core feature of neuropsychiatric illness. We offer a framework or conceptualizing cognitive function and discuss bedside examination and neuropsychological assessment, as well as the limitations of these tools. We stress the clinical importance of executive cognitive dysfunction, and we provide guidance or its assessment. PMID- 11782893 TI - Interferon-gamma therapy: evaluation of routes of administration and delivery systems. AB - Although different routes and delivery systems have been used to deliver interferon-gamma (IFN-gamma) for the treatment of a variety of viral and neoplastic diseases, little has been reported regarding the most efficient and least toxic routes and drug delivery modes required to achieve these goals. To have a greater understanding of the best strategies to use to administer this cytokine in an efficient, stable, and safe manner, this review details aspects of IFN-gamma concerning its mechanism of action, physical properties, and pharmacokinetics. One important conclusion that is drawn from this analysis is that a consistent, local concentration of IFN-gamma is necessary to achieve an optimal therapeutic response. A critical discussion covering the advantages and limitations of the currently used methodologies to deliver IFN-gamma in such a fashion is presented. PMID- 11782894 TI - Pharmacokinetic/pharmacodynamic studies in drug product development. AB - In the quest of ways for rationalizing and accelerating drug product development, integrated pharmacokinetic/pharmacodynamic (PK/PD) concepts provide a highly promising tool. PK/PD modeling concepts can be applied in all stages of preclinical and clinical drug development, and their benefits are multifold. At the preclinical stage, potential applications might comprise the evaluation of in vivo potency and intrinsic activity, the identification of bio-/surrogate markers, as well as dosage form and regimen selection and optimization. At the clinical stage, analytical PK/PD applications include characterization of the dose-concentration-effect/toxicity relationship, evaluation of food, age and gender effects, drug/drug and drug/disease interactions, tolerance development, and inter- and intraindividual variability in response. Predictive PK/PD applications can also involve extrapolation from preclinical data, simulation of drug responses, as well as clinical trial forecasting. Rigorous implementation of the PK/PD concepts in drug product development provides a rationale, scientifically based framework for efficient decision making regarding the selection of potential drug candidates, for maximum information gain from the performed experiments and studies, and for conducting fewer, more focused clinical trials with improved efficiency and cost effectiveness. Thus, PK/PD concepts are believed to play a pivotal role in streamlining the drug development process of the future. PMID- 11782895 TI - Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. AB - Daflon 500 mg, is a micronized purified flavonoid fraction, containing 90% w/w diosmin and 10% w/w of flavonoids expressed as hesperidin, used clinically in the treatment of chronic venous insufficiency and hemorrhoidal disease. This study was designed to investigate the influence of particle size on the overall absorption of diosmin after oral administration of micronized (mean particle size = 1.79 microm, with 80% of particles having a size lower than 3.45 microm) and nonmicronized diosmin (mean particle size = 36.5 microm, with 80% of particles comprised between 19.9 and 159 microm). In a double blinded, cross-over study design, 500 mg tablets containing trace amounts (approximately 25 nCi) of (14)C diosmin were administered to 12 healthy male volunteers as a single oral dose. Accelerator mass spectrometry and liquid scintillation counting were used for the measurement of (14)C-diosmin in urine and feces. Absorption of (14)C-diosmin from the gastrointestinal tract, measured by the urinary excretion of total radioactivity, was significantly improved with the micronized (57.9 +/- 20.2%) compared with the nonmicronized material (32.7 +/- 18.8%). Statistical comparison of the urinary excretion of the two pharmaceutical formulations showed this difference to be highly significant (p = 0.0004, analysis of variance). The overall excretion of the radiolabeled dose was 100% with mean +/- SD of 109 +/- 23% and 113 +/- 20% for the micronized and nonmicronized forms, respectively. The results of this study show: 1. the impact of a reduction of particle size on the extent of absorption of diosmin, giving a pharmacokinetic explanation to the better clinical efficacy observed with the micronized formulation, and 2. the use of accelerator mass spectrometry in conjunction with liquid scintillation counting in measurement of bioavailability in a human cross-over study comparing two drug formulations containing trace amounts of radioactivity. PMID- 11782896 TI - Pharmacokinetics and pharmacological effect of lerisetron, a new 5-HT3 antagonist, in rats. AB - The pharmacokinetics of lerisetron, a novel 5HT(3) antagonist, are studied together with its efficacy in inhibiting the serotonin (5-HT)-evoked transient bradycardia reflex (von Bezold-Jarisch reflex) in Sprague Dawley rats. [(14)C]Lerisetron (50, 100, and 200 microg/kg) was given to rats by intravenous (iv) injection and plasma levels of unchanged (UL) and total (unchanged + changed, TL) drug were measured by liquid chromatography with radioactivity monitoring and scintillation counting, respectively. Linearity of UL and TL pharmacokinetics over the dose range was established by noncompartmental analysis. Protein binding of lerisetron was measured in vitro by ultrafiltration. The unbound fraction was 14.4 +/- 1.4%. A nonlinear mixed effects ("population") bicompartmental pharmacokinetic analysis showed that volume of distribution and clearance (CL) were high for both forms of the drug, but CL was significantly smaller for TL [(mean +/- SEM) 0.014 +/- 0.03 L/min for UL versus 0.006 +/- 0.03 L/min for TL, p < 0.05)]. Large interindividual variabilities were observed for both forms. The response to lerisetron administration (inhibition of bradycardia) was evaluated at different doses (2, 3, 5, 6, and 10 microg/kg, iv) at times 2 180 min after dose administration and related to simulated concentrations. Inhibition was 100% 5 min after the 10-microg/kg dose and, 3 h later, it was still > 10%. Response to lerisetron was dose related in the range studied. Pharmacodynamic parameters were estimated by a sigmoid E(max) naive-pooled model. The parameters were also different between the two forms: EC(50) was 0.44 ng/mL (CV = 5.9%) for UL and 0.88 ng/mL (CV = 4.9%) for TL. We conclude that UL and TL pharmacokinetics were linear and that the differences in the kinetics and dynamics between the two forms suggest the presence of at least one metabolite. PMID- 11782897 TI - Different Mg to Fe ratios in the mixed metal MgFe hydroxy-carbonate compounds and the effect on phosphate binding compared with established phosphate binders. AB - Due to the side effects of the current oral phosphate binders, there is a need for effective alternatives. A number of mixed metal hydroxy-carbonate compounds (MMHCs) based on Mg and Fe have recently been established as effective phosphate binders. We have now carried out further studies on the MMHCs with different ratios of Mg(2+):Fe(3+) in different forms to assess for phosphate binding efficacy and ionic release in aqueous solution and food slurries. The compounds that provide the most promise are those with Mg(2+):Fe(3+) ratios of 2:1 and 4:1 in the unaged/dry form. Their phosphate binding efficacy was compared with a wide range of established phosphate binders, such as aluminum hydroxide [Al(OH)(3)], calcium carbonate (CaCO(3)), calcium acetate (CaAc(2)), magnesium hydroxide [Mg(OH)(2)], and lanthanum carbonate [La(2)(CO(3))(3)] in various food slurries. The results showed that the MgFe compounds were much more effective (on a weight for weight basis) than the established binders, and their properties were relatively pH independent. Calcium compounds (CaCO(3) and CaAc(2)) were ineffective under the experimental conditions. Mg(OH)(2) was effective at low pH but not at pHs greater than 5.0, and also released two- to threefold more magnesium than the MgFe compounds. Al(OH)(3) showed some degree of efficacy, but the binding capacity was, at best, less than 50% of the MMHCs. La(2)(CO(3))(3) required at least a 10-fold increase in weight to give comparable binding to the MMHCs. In conclusion, MgFe hydroxy-carbonate compounds are effective phosphate binders and may provide a better alternative to both existing and emerging binders for combating hyperphosphataemia. PMID- 11782898 TI - Maximizing the in vivo efficiency of gene transfer by means of nonviral polymeric gene delivery vehicles. AB - We have screened many synthetic and natural polymers for their ability to facilitate gene delivery in vivo into subcutaneous tissue. We postulated that gene delivery polymeric vehicles could control the chemical and biological stability of plasmid as well as their colloidal and surface properties, and this may lead to enhanced gene delivery in vivo. The screening was based on reporter gene (luciferase) expression using a plasmid containing the cytomegalovirus promoter. The control of charge density of resulting particles was achieved by selecting different ratios of polymer to plasmid mass as well as polymer chemistry. As opposed to in vitro observations, only polymers that lead to negatively charged particles exhibited an in vivo activity, in opposite to in vitro case. Such polymers exhibited relatively low positive charge chemistry (or neutral charge). The most potent polymeric vehicles were members of a Tetronic polymer series (synthetic polyethylene-polypropylene block copolymers; BASF, Mount Olive, NJ) or from a noncharged polyvinylpyrrolidine formulation. Plasmid dose response and time relationships were established for some polymers. Results were applied to the redesign of particles for biolistic (gene gun) plasmid gene delivery. PMID- 11782899 TI - Peppermint oil enhances cyclosporine oral bioavailability in rats: comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole. AB - Peppermint oil inhibits cyclosporine metabolism in vitro. The current work compared the effects of peppermint oil, ketoconazole, and D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) on cyclosporine oral bioavailability. Male Sprague-Dawley rats were administered cyclosporine (25 mg/kg) as the Sandimmune formulation. Peppermint oil (100 mg/kg) tripled the mean cyclosporine maximum concentration (C(max)) from 0.60 to 1.6 microg/mL and increased the area under the concentration versus time curve (AUC(0-infinity)) from 8.3 to 24.3 microg x h/mL. The median time to reach C(max) (t(max)) was increased from 2 to 6 h. Terminal half-life (10 h) and mean residence time (MRT; 15 h) were unaffected. Coadministration of TPGS (50 mg/kg) with cyclosporine in a saline vehicle doubled cyclosporine C(max) from 1.3 to 2.9 microg/mL and increased AUC(0-infinity) from 28.5 to 59.7 microg x h/mL. The t(max) was unchanged (3 h). Terminal half-life and MRT were increased by 44% (15.4 versus 10.7 h) and 24% (19.9 versus 16.0 h), respectively. Cyclosporine pharmacokinetics were not altered when corn oil was used instead of saline as a gavage vehicle, however the TPGS effect was abolished. Ketoconazole (10 and 20 mg/kg) had no effect on cyclosporine absorption. The lack of a significant ketoconazole effect may reflect poor metabolism of cyclosporine in rat intestinal tissue and suggests that inhibition of cytochrome P450 3A is not the only means by which peppermint oil enhances cyclosporine oral bioavailability. PMID- 11782900 TI - Synergistic effect of low-frequency ultrasound and surfactants on skin permeability. AB - Low-frequency ultrasound (20 kHz) and surfactants have been individually shown to enhance transdermal drug transport. In this study, we investigated the synergistic effect of ultrasound and surfactants on transdermal drug delivery. Surfactants with different head group chemistries including anionic, cationic, and nonionic with varying tail lengths (8-16-carbon atoms) were studied. We found that surfactants possessing anionic and cationic head groups were more potent than those possessing nonionic head groups in increasing skin conductivity in the presence of ultrasound. Furthermore, for surfactants possessing the same head group, those with a 14-carbon tail length were found to be most effective in enhancing skin permeability. The data presented in this report show that ultrasound and surfactants synergistically enhance skin permeability. Two mechanisms are shown to play a role in this synergistic effect. First, ultrasound enhances surfactant delivery (enhanced delivery) into the skin and, second, ultrasound disperses surfactant (enhanced dispersion) within the skin. In general, surfactants that are potent enhancers by themselves are potent enhancers in the presence of ultrasound as well. We performed imaging experiments to assess the effect of ultrasound on delivery of a model permeant, sulforhodamine B, into the skin. These experiments show that ultrasound enhances surfactant delivery and dispersion in the skin. PMID- 11782901 TI - Topical formulation studies with DEET (N,N-diethyl-3-methylbenzamide) and cyclodextrins. AB - The purpose of this study was to investigate the utility of cyclodextrins as a safer alternative to the commonly used cosolvent ethanol in topical N,N-diethyl-3 methylbenzamide (DEET) formulations. Ethanol is a known penetration enhancer and would ideally not be used in a formulation containing DEET, a compound known for its potential toxicity. DEET formulations were prepared containing up to 20% w/w gamma-cyclodextrin (GCD) or 30% w/w hydroxypropyl-beta-cyclodextrin (HPBCD). These formulations were evaluated by determining the release rate of DEET from its vehicle through a synthetic membrane into a receiver medium with a high affinity for DEET using a fully automated Franz-diffusion cell system. DEET release was measured by ultraviolet spectrophotometry at 260 nm. Both the traditional Higuchi release model and an alternate repeated measures analysis of variance with nested factors were used to analyze the data. The influence of the cyclodextrins on the volatility of DEET was determined by solid-phase microextraction. Morphological characterization of the formulations was performed by light microscopy. Physical stability of the formulations was evaluated by rheology in an accelerated study performed at 50 degrees C for 28 days. The cyclodextrins caused a decrease in the release of DEET from its vehicle compared with an ethanol-containing formulation. This effect became more pronounced as the amount of cyclodextrin in the formulation was increased. The addition of the cyclodextrins resulted in a cream-like product compared with the ethanol formulation, which was a lotion. The DEET formulations had the following rank order of volatility: ethanol < DEET = GCD < HPBCD. Examination of the formulations by light microscopy indicated that the CD-based formulations produced a smaller and more homogeneous droplet size distribution than the ethanol-based formulations. The accelerated physical stability study indicated that cyclodextrin-based formulations are both technically and commercially feasible. Cyclodextrins are a promising alternative to ethanol in DEET-containing formulations. The reduced release rate of DEET from these formulations suggests that the toxic potential of DEET may be decreased in these products, while its repellency and stability are maintained. PMID- 11782902 TI - Preformulation study of epigallocatechin gallate, a promising antioxidant for topical skin cancer prevention. AB - Epigallocatechin gallate (EGCG) is a potent polyphenolic antioxidant extracted from green tea. Due to its antimutagenic and antitumor activities, it is a promising candidate for use in topical formulations for skin cancer prevention. The overall goal of this study was therefore to determine the influence of several factors on the stability of EGCG in solution to obtain information that would facilitate the subsequent development of topical formulations. Our first objective was to determine the influence of pH, temperature, and ionic strength on the aqueous stability of EGCG. A second objective was to determine the stability of EGCG in various solvents in the presence and absence of different antioxidants. A simple and rapid stability indicating high-performance liquid chromatography assay for EGCG was developed. Stability studies were performed in 0.05 M aqueous buffers at pH 3, 5, 7, and 9 at 4, 25, and 50 degrees C. The effect of ionic strength on EGCG stability was evaluated in 0.05 M acetate buffer, pH 5, adjusted to the desired ionic strength with sodium chloride. An accelerated stability study of EGCG was performed at 50 degrees C in the organic solvents glycerin and Transcutol P in the presence of antioxidants. The degradation of EGCG increased rapidly as temperature and solution pH were increased. Ionic strength increases also caused an accelerated degradation. The solution stability of EGCG was prolonged in glycerin and Transcutol P compared with an aqueous environment. The addition of 0.1% concentrations of several antioxidants in combination with 0.025% EDTA caused variable effects on EGCG stability. Butylated hydroxytoluene in glycerin produced the greatest stability improvement for EGCG. The t(90) (time for 10% degradation to occur) was 76.1 days at 50 degrees C. It can be concluded that glycerin-based vehicles are suitable for stabilizing EGCG. PMID- 11782903 TI - Investigation of the coordinated functional activities of cytochrome P450 3A4 and P-glycoprotein in limiting the absorption of xenobiotics in Caco-2 cells. AB - The coordination of the functional activities of intestinal CYP3A4 and P-gp in limiting the absorption of xenobiotics in Caco-2 cells was investigated. Growing Caco-2 cells were exposed to increasing concentrations of doxorubicin (1-2 microM) in plastic flasks to encourage a subpopulation of cells, that displayed an intrinsically higher multidrug resistance (mdr) phenotype than the parent cells, to survive and grow. Doxorubicin-exposed (hereinafter referred to as type I cells) and nonexposed Caco-2 cells (parent cells) on collagen-coated inserts were also treated with either 0 (control) or 0.25 microM 1alpha,25 dihydroxyvitamin D(3) to promote cellular CYP3A4 expression. Increased P-gp protein expression, as detected by Western blotting, was noted in type I cells (213 +/- 54.35%) compared to that of parent cells (100 +/- 6.05%). Furthermore, they retained significantly less [(3)H]vincristine sulphate (p < 0.05), a P-gp substrate, after efflux (272.89 +/- 11.86 fmol/mg protein) than the parent cells (381.39 +/- 61.82 fmol/mg protein). The expression of CYP3A4 in parental cells after 1alpha,25-dihydroxyvitamin D(3) treatment was quantified to be 76.2 +/- 7.6 pmol/mg protein and comparable with that found in human jejunal enterocytes (70.0 +/- 20.0 pmol/mg protein). Type I cells, however, expressed a very low quantity of CYP3A4 both before and after the treatment that was beyond the minimum detection limit of Western blotting. Functionally, the rates of 1-hydroxylation of midazolam by CYP3A for both cell types ranged from 257.0 +/- 20.0 to 1057.0 +/ 46.0 pmol/min/mg protein. Type I cells, although having a higher P-gp expression and activity comparatively, metabolized midazolam less extensively than the parent cells. The results suggested that there were noncoordinated functional activities of intestinal CYP3A4 and P-gp in Caco-2 cells, although they both functioned independently to minimize intestinal epithelial absorption of xenobiotics. PMID- 11782904 TI - Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. AB - In drug discovery and nonclinical development the volume of distribution at steady state (V(ss)) of each novel drug candidate is commonly determined under in vivo conditions. Therefore, it is of interest to predict V(ss) without conducting in vivo studies. The traditional description of V(ss) corresponds to the sum of the products of each tissue:plasma partition coefficient (P(t:p)) and the respective tissue volume in addition to the plasma volume. Because data on volumes of tissues and plasma are available in the literature for mammals, the other input parameters needed to estimate V(ss) are the P(t:p)'s, which can potentially be predicted with established tissue composition-based equations. In vitro data on drug lipophilicity and plasma protein binding are the input parameters used in these equations. Such a mechanism-based approach would be particularly useful to provide first-cut estimates of V(ss) prior to any in vivo studies and to explore potential unexpected deviations between sets of predicted and in vivo V(ss) data, when the in vivo data become available during the drug development process. The objective of the present study was to use tissue composition-based equations to predict rat and human V(ss) prior to in vivo studies for 123 structurally unrelated compounds (acids, bases, and neutrals). The predicted data were compared with in vivo data obtained from the literature or at Roche. Overall, the average ratio of predicted-to-experimental rat and human V(ss) values was 1.06 (SD = 0.817, r = 0.78, n = 147). In fact, 80% of all predicted values were within a factor of two of the corresponding experimental values. The drugs can therefore be separated into two groups. The first group contains 98 drugs for which the predicted V(ss) were within a factor of two of those experimentally determined (average ratio of 1.01, SD = 0.39, r = 0.93, n = 118), and the second group includes 25 other drugs for which the predicted and experimental V(ss) differ by a factor larger than two (average ratio of 1.32, SD = 1.74, r = 0.42, n = 29). Thus, additional relevant distribution processes were neglected in predicting V(ss) of drugs of the second group. This was true especially in the case of some cationic-amphiphilic bases. The present study is the first attempt to develop and validate a mechanistic distribution model for predicting rat and human V(ss) of drugs prior to in vivo studies. PMID- 11782905 TI - Intracellular uptake and trafficking of Pluronic micelles in drug-sensitive and MDR cells: effect on the intracellular drug localization. AB - The intracellular uptake and localization of a fluorescently labeled Pluronic P 105 in HL-60 leukemia cells and in A2780 drug-sensitive and A2780/ADR MDR ovarian carcinoma cells were characterized by flow cytometry and fluorescence microscopy. Pluronic P-105 molecules were labeled with a pH-sensitive fluorescent label, 5 (and 6-)carboxy-2'7'-dichlorofluorescein. The fluorescence intensity of labeled Pluronic was about twofold higher at pH 7.4 than at pH 5.5. At Pluronic concentrations exceeding the critical micelle concentration (cmc), flow cytometry histograms manifested bimodal distribution of cell fluorescence for all types of cells. Cell population characterized by higher fluorescence intensity presumably resulted from Pluronic transfer from the acidic environment of cytoplasmic vesicles (endosomes or lysosomes) into the neutral environment of the cytoplasm and cell nuclei, which suggested the permeabilization of the membranes of acidic vesicle by Pluronic molecules. For the MDR cells, the bimodal distribution of cell fluorescence was already observed at very low Pluronic concentrations in the incubation medium (i.e., below the cmc). The data suggest that the membranes of acidic vesicles of MDR cells are more susceptible to the action of polymeric surfactants than those of drug-sensitive cells. Permeabilization of acidic vesicles had a dramatic effect on the intracellular trafficking of drugs: when delivered in PBS, the anthracyclin drug ruboxyl (Rb) sequestered in cytoplasmic vesicles and was excluded from cell nuclei; however, when delivered in Pluronic micelles, drug accumulated in cell nuclei. Drug uptake from/with Pluronic micelles was substantially enhanced by ultrasound. These findings suggest that the nuclear accumulation of drugs internalized via fluid-phase endocytosis can be enhanced by the application of Pluronic micelles and can be further augmented by ultrasonic irradiation. PMID- 11782906 TI - New oligoethylene ester derivatives of 5-iodo-2'-deoxyuridine as dermal prodrugs: synthesis, physicochemical properties, and skin permeation studies. AB - Five new oligoethylene ester derivatives (9-13) of 5-iodo-2'-deoxyuridine (IDU) were synthesized and assayed to determine their lipophilicity by both experimental lipophilicity indices (log K') and calculated partition coefficients (CLOGP). In vitro experiments were carried out to evaluate the chemical and enzymatic stability and fluxes through excised human skin of these new IDU derivatives. Esters 9-13 showed increased lipophilicity compared with the parent drug (IDU), had good stability in phosphate buffer (pH 7.4), and were readily hydrolyzed by porcine esterase. No correlation between lipophilicity and skin permeation fluxes of synthesized esters 9-13 was observed. Results from in vitro percutaneous absorption studies showed that, among all esters synthesized, only esters 9 and 10 significantly increased the cumulative amount of IDU that penetrated through excised human skin compared with the parent drug (IDU). PMID- 11782907 TI - The effect of salts on the micellization temperature of aqueous poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) solutions and the dissolution rate and water diffusion coefficient in their corresponding gels. AB - Studies were performed to examine the effect of ionic salts on phase transitions, dissolution rates, and diffusion coefficients of water in gels of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) with polymer concentrations ranging from 22 to 32% w/w and salt concentrations ranging from 0 to 1.5% w/w. Salts tested include Na(3)PO(4), Na(2)SO(4), Na(2)HPO(4), NaH(2)PO(4), NaCH(3)CO(2), NaCl, and KI. Micellization transition temperatures were obtained using differential scanning calorimetry. The dissolution rates were obtained by measurement of the surface erosion rates, and diffusion coefficients were obtained by using a method to analyze the intrusion of water into the aqueous gels. It was found that salts had no effect on the dissolution rate of the polymer gels into deionized water. However, when the salt concentration in the aqueous dissolution media was adjusted to match the concentration in the gels, the dissolution rate of the polymer gel decreased with increasing salt concentration. The salts also had a profound effect on the critical micellization temperature (CMT) and the diffusion coefficient of water within the gel. The diffusion coefficient and CMT decreased in the presence of salts. The magnitude of these effects was comparable to their placement on the Hofmeister, or lyotropic series for salts. The effects of polymer and salt concentrations on the CMT were quantified, and a single correlation was proposed to predict the micellization temperatures for a wide range of salt and polymer concentrations. PMID- 11782908 TI - Enhanced human nail drug delivery: nail inner drug content assayed by new unique method. AB - The purpose of this study was to develop an assay method of the human inner nail plate and to compare nail drug penetration by a penetrating enhancing formulation (the test carrier formulation). The test carrier and saline formulations were tested using radiolabeled urea, ketoconazole, and salicylic acid. After twice dosing daily for 7 days on human nail plates, the under inner section of the nail plate was assayed for absorbed drug content using a unique drilling/removal system. Results show that the weight-normalized radioactivity contents of three chemicals in the inner intermediate nail plate center in the carrier formulation were two fold higher than those from saline (p < 0.05). Total radioactivity recovery of dosed [(14)C]-salicylic acid was 89 +/- 2% in the carrier formulation and 88 +/- 5% in saline. In saline formulation, salicylic acid showed greater binding to the outer nail, making it less bioavailable for the inner nail area. This didn't occur with carrier formulation. In conclusion, topical treatment of nail diseases such as onychomycosis is not yet sufficiently effective, likely because of minimal drug penetration into the inner nail plate where the disease perpetuates. The assay system has the unique characteristic of being able to assay the inner part of the nail where the disease resides. PMID- 11782909 TI - A recirculatory model for local absorption and disposition of ciprofloxacin by measuring portal and systemic blood concentration difference. AB - A recirculatory model for the portal-systemic blood concentration difference (P-S difference) was developed to separately evaluate the rate and extent of absorption from the gastrointestinal tract into the portal system and disposition of a drug in the body. To apply this model to pharmacokinetic analysis, ciprofloxacin was selected as a model drug possessing a moderate intestinal absorption, and renal and hepatic elimination. The portal and systemic blood samples were simultaneously taken from rats at appropriate time points after intravenous and oral administration of ciprofloxacin at a dose of 5 mg/kg. After intravenous administration, little or no difference in the concentrations between the portal and systemic blood was observed, whereas after oral administration the concentrations of ciprofloxacin in the portal blood were consistently higher than those in the systemic blood over the time studied. This difference observed after oral administration is attributed to the absorption of ciprofloxacin from the gastrointestinal tract into the portal system. On the basis of the moment analysis deduced from the recirculatory model, the portal blood flow rate (Q(p)), the local absorption ratio from the gastrointestinal tract into the portal system (F(a)), the hepatic recovery ratio (F(h)), and bioavailability (BA) were then estimated. The obtained Q(p) of 2.81 L/h/kg, F(a) of 32.6, F(h) of 68.1, and BA of 22.2% were found to be in good agreement with the reported values. Furthermore, the mean local absorption time from the gastrointestinal tract into the portal system (t(a)) calculated by a nonlinear least-squares program [MULTI (FILT)] was almost identical with that by the global moments. These results suggest that the model proposed in this study would be useful for evaluating both in vivo absorption and disposition of drugs. PMID- 11782910 TI - Investigation of protein/carbohydrate interactions in the dried state. 1. Calorimetric studies. AB - Isoperibol calorimetry was used to evaluate protein/carbohydrate interactions after freeze drying. rh-DNase, rh-GH, rh-MetGH, and rh-IGF-I were freeze dried with either mannitol, sucrose, trehalose, or dextran at concentrations ranging from 0% to 100% (w/w). Enthalpies of solution for both freeze-dried and physical mixtures were measured in water at 25 degrees C. Differential scanning calorimetry was used to monitor changes in the melting or crystallization temperatures of the lyoprotectants. Linear relationships between enthalpies of solution and the percentage of protein in the formulations were observed for all physical mixtures. In contrast, nonlinear relationships between the enthalpies of solution and protein content were observed for the freeze-dried mixtures. Mannitol-containing mixtures were characterized by negative deviation from linearity, while positive deviations were detected for mixtures containing sucrose or trehalose. Using DSC, sucrose was found to be amorphous at low and not detected at high protein content in the freeze-dried mixtures. Melting of mannitol was observed through almost all of the protein concentration range examined. Two melting endotherms, however, were observed for mannitol at most protein/mannitol ratios, indicating the presence of protein/mannitol interactions. This work suggests that direct interactions occur between proteins and carbohydrates in lyophilized mixtures. PMID- 11782911 TI - Intestinal absorption and presystemic elimination of the prokinetic agent, EM574, in the rabbit. AB - The purpose of this study was to characterize the pharmacokinetics and dose proportionality of the prokinetic macrolide, EM574, in rabbits following intravenous dosing, and to determine the intestinal absorption and intestinal and hepatic first-pass elimination of EM574 in rabbits. Two doses (0.05 and 0.25 mg/kg) of EM574 were given to rabbits intravenously in a crossover study. In a separate gut perfusion study, rabbit duodenal or jejunal segments were perfused with EM574 solution at 0.2 mL/min for 130 min. Plasma levels of EM574 were determined by a validated LC-MS/MS assay, and concentrations in perfusate were determined by HPLC with UV detection. The absorptive clearance (PeA) of EM574 was calculated from the steady-state rate of disappearance from the gut lumen during perfusion. The cumulative amount (A(app)) of drug appearing in the systemic circulation was calculated by deconvolution, where the input response was the plasma concentration-time profile during intestinal perfusion and the unit impulse response was the mean profile following intravenous bolus dosing to sham operated rabbits in a separate experiment. F(g)F(h) was calculated from the ratio of A(app) to the total amount disappeared from gut lumen during perfusion. Hepatic first-pass elimination was measured by intraportal venous infusion. EM574 exhibits linear kinetics over the dose range studied. CL, V(ss), and terminal half-life (mean +/- SD) of EM574 were 68.6 +/- 15.5 mL/min/kg, 13.4 +/- 3.0 L/kg, and 2.7 +/- 0.8 h, respectively. EM574 is expected to be absorbed completely from the rabbit small intestine based on its high jejunal PeA values (8.1 +/- 2.2, and 5.5 +/- 1.5 microL/min/cm following low and high dose perfusion, respectively). The first-pass extraction of EM574 was substantial and dose independent. Mean F(g) and F(h) were 0.14 and 0.20, respectively, suggesting that the intestinal and hepatic first-pass elimination of EM574 were comparable. Deconvolution was successfully applied in the determination of gut wall and hepatic first-pass elimination of EM574. PMID- 11782912 TI - The solid-state stability of amorphous quinapril in the presence of beta cyclodextrins. AB - The major objective of this study was to investigate the effects of beta cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the solid-state chemical reactivity of the drug, quinapril, when amorphous samples are prepared by colyophilization of quinapril and each of these beta-CDs. For comparison, a physical mixture with beta-CD and colyophilized mixtures with trehalose and dextran were also prepared and subjected to a similar chemical stability test at 80 degrees C followed by HPLC analysis. Significant inhibition of degradation was observed only for colyophilized miscible mixtures with beta-CD and HP-beta-CD at molar ratios in excess of 1:1. Colyophilized mixtures with trehalose and dextran, shown to have phase separated, and the physical mixture with beta-CD exhibited no inhibiting effects. This suggests that specific molecular complexation is responsible for the significant inhibition by the beta CDs. The tendency of quinapril to form molecular complexes in solution with the beta-CDs was measured by (1)H solution NMR, by estimating complexation constants from the chemical shift of specific groups on quinapril. Supporting evidence for solid-state complexation was provided by FTIR analysis. DSC and TSC measurements indicated that the beta-CDs do not have high enough glass transition temperatures to reduce reactivity by reducing molecular mobility. PMID- 11782913 TI - Interaction of nonpeptidic delta agonists with P-glycoprotein by in situ mouse brain perfusion: liquid chromatography-mass spectrometry analysis and internal standard strategy. AB - Many opioids are substrates of the efflux transporter P-glycoprotein (P-gp) in the blood-brain barrier (BBB). In situ brain perfusion in wild-type and mdr 1a(-/ ) P-gp-deficient mice was utilized to investigate potential P-gp-mediated transport of novel nonpeptidic delta agonists (AR-M delta compounds). Because radioactive compounds were not available for this series, liquid chromatography mass spectrometric detection (LC-MS) was the assay methodology of choice. Verapamil in the perfusion buffer (0.5 microM) served as a positive control for P gp-mediated efflux and as an experimental internal standard for P-gp modulation by AR-M delta compounds. LC-MS provided excellent assay sensitivity with no significant interferences. In P-gp-competent mice, the brain extraction of AR-M delta compounds ranged from 1.1 to 96%. The ratio of initial brain uptake clearances (Cl(up)) in P-gp-deficient and wild-type mice (P-gp effect) ranged from 0.96 to 4.91. Some compounds increased the Cl(up) of verapamil in P-gp competent mice, consistent with P-gp inhibition. These results demonstrate that LC-MS is an appropriate assay methodology for mouse brain perfusion samples, that AR-M delta compounds may interact with P-gp in the BBB, and that the internal strategy can provide useful information concerning P-gp modulation by compounds of interest. PMID- 11782914 TI - New findings on degradation of famotidine under basic conditions: identification of a hitherto unknown degradation product and the condition for obtaining the propionamide intermediate in pure form. AB - The degradation behavior of famotidine (1) was investigated in 25% ammonia solution and in 2 M NaOH. The hydrolysis of the drug in ammonia resulted in separation of [3-[[2-[(diaminomethylene)amino]-4 thiazolyl]methyl]thio]propionamide (3), an impurity listed in British Pharmacopoeia. The treatment with 2 M NaOH resulted in formation of [3-[[[2 [(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionyl]sulfamide (2) and 3. These products further decomposed to [3-[[2-[(diaminomethylene)amino]-4 thiazolyl]methyl]thio]propionic acid (4) and a heretofore unknown product, 5. The latter separated out in the reaction mixture as brown shiny crystals. Proton and carbon-13 nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis of the charcoal-treated product established the structure. The formation of 5 is postulated to involve abstraction of a proton from the alpha carbon of intermediates 2 and 3 followed by elimination of the thiol moiety. PMID- 11782915 TI - Improvement of dissolution and oral absorption of ER-34122, a poorly water soluble dual 5-lipoxygenase/cyclooxygenase inhibitor with anti-inflammatory activity by preparing solid dispersion. AB - Several formulation approaches were attempted to improve the dissolution and the oral absorption of ER-34122, which is a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity. The solid dispersion of ER 34122 with hydroxypropylmethylcellulose (TC-5RW), which is an inert solid carrier, resulted in a significant improvement in the dissolution rate of ER 34122. The solid dispersion was prepared by a solvent evaporation method using ethanol and water. The solid-state characteristics of the solid dispersion, the corresponding physical mixture, and ER-34122 alone were investigated by X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and an automated controlled-atmosphere microbalance. The X-ray powder diffraction patterns suggest that the solid dispersion exists in a totally amorphous state and the others exist in a crystalline state. The FTIR spectra results suggest that ER-34122 can interact with TC-5RW through intermolecular hydrogen bonding in the solid dispersion. This interaction may cause a stabilization of ER-34122 in the higher-energy, faster-dissolving amorphous state. The dissolution rate of ER 34122 from the solid dispersion was significantly greater than that from the physical mixture or the pure drug. Furthermore, when orally administrated to beagle dogs, ER-34122 showed about a 100-fold increase in both maximum concentration (C(max)) and area under the curve of concentration versus time (AUC) compared with the pure drug. Consequently, it was determined that the solid dispersion technique with TC-5RW provides a promising way to increase the dissolution rate and the oral absorption of poorly water-soluble drugs such as ER 34122. PMID- 11782916 TI - Mechanism of lidocaine release from carbomer-lidocaine hydrogels. AB - Rheology, acid-base behavior, and kinetics of lidocaine release of carbomer lidocaine (C-L) hydrogels are reported. A series of (C-L)(x) (x = mol% of L = 25, 50, 75, 100) that covers a pH range between 5.33 and 7.96 was used. Concentrations of ion pair ([R-COO(-)LH(+)]) and free species (L) and (LH(+)) were determined by the selective extraction of (L) with cyclohexane (CH) together with pH measurements, i.e., CH in a ratio CH/hydrogel 2:1 extracted 48% of the whole concentration of lidocaine [L(T)] of a (C-L)(100), [[L(T)] = ([R-COO( )LH(+)]) + (L) + (LH(+))]. The remaining species in the aqueous phase were distributed as: (L) 3.82%, (LH(+)) 14.5%, and [R-COO(-) LH(+)] 81.7%. Rheology and pH as a function of (C-L) concentration are also reported. Delivery rates of free base L were measured in a Franz-type bicompartmental device using water and NaCl 0.9% solution as receptor media. (C-L) hydrogels behave as a reservoir that releases the drug at a slow rate. pH effects on rate suggest that, under the main conditions assayed, dissociation of [R-COO(-)LH(+)] is the slow step that controls releasing rates. Accordingly, release rate was increased upon addition of a second counterion (i.e., Na(+)), or through the diffusion of neutral salts such as NaCl, into the matrix of the gel. PMID- 11782917 TI - Identification of the most relevant factors that affect and reflect the quality of granules by application of canonical and cluster analysis. AB - The production of granules by wet granulation in a fluidized bed was assessed according to two statistical techniques to identify the most relevant factors that affect the quality of the granules. The statistics used include Canonical Analysis and Cluster Analysis. The factors studied, according to a center of gravity design, included the solubility of a model drug, different grades of polyvinylpirrolidone (PVP), the polarity and the rate of administration of the granulation solution, the atomizing air pressure, the inlet air pressure and rate. The properties of the granules considered were the yield, the assay of the drug, the size, the densities (true, bulk and tapped), the friability, the flowability and one compressibility index. Statistical analysis of the factors evaluated has shown that the solubility of the materials and the pressure of the atomizing air in the nozzle were the most critical parameters affecting the quality of the granules. Less relevant were the granulation solution and the grade of PVP. The properties of the granules that best described their quality were the yield and the densities. From the Cluster Analysis it was possible to divide the granules in two clusters, where cluster 1 was identifiable by the yield, the assay, the flowability, and the friability, whereas cluster 2 was better identified by the size of the granules. PMID- 11782918 TI - Starch acetate--a novel film-forming polymer for pharmaceutical coatings. AB - Starch acetates (SA) have been investigated as novel, multifunctional excipients for the direct compression tableting process. In this study, the film-forming ability of SA (DS 2.8) and the effect of commonly used plasticizers on the physical properties of SA films were evaluated. The results were compared with the properties of ethylcellulose (EC). Free films were prepared by a solvent-cast method. Mechanical studies, water vapor and drug permeability tests, and thermal analysis (DSC) were used to characterize the film-forming ability of SA and efficiency of tested plasticizers. SA films were tougher and stronger than EC films at the same plasticizer concentration. Also, in most cases, the water vapor permeability of SA films was lower than that of EC films. DSC thermograms supported the findings of the tensile test: plasticizers with several small ester groups (e.g., triacetin and triethyl citrate) were the most compatible with SA. Due to the good mechanical properties, low water vapor, and drug permeabilities of the films, SA seems to be a promising film-former for pharmaceutical coatings. The toughness of SA films may result from their dense film structure, which is due to strong interaction forces between adjacent SA molecular chains. PMID- 11782919 TI - In vitro assessment of intestinal IGF-I stability. AB - Insulin-like growth factor (IGF-I) is a 7648-Da polypeptide consisting of 70 amino acids. Clinically, IGF-I might be used in type II diabetes, which requires a life-long treatment. Therefore, delivery routes other than parenteral injections are highly desirable. For convenience, the peroral route is the most attractive. Therefore, in an attempt to answer the feasibility of oral delivery of IGF-I we examined the metabolism of this polypeptide in the gut in the presence of crude porcine pancreatic enzymes (CPPE) and flushings of the small and large intestine from pig, rat, and dog. Moreover, incubation studies with purified pancreatic enzymes that are present in the intestine were performed to determine the most active enzymes responsible for the intestinal cleavage of IGF I. IGF-I was mainly degraded by chymotrypsin (t(1/2) = 2.7 min) and trypsin (t(1/2) = 34.6 min), whereas in the presence of aminopeptidase M and carboxypeptidase A IGF-I was stable up to 90 min. IGF-I was degraded in flushings from the jejunum, ileum, and colon. However, there were no significant differences in the stability of IGF-I between the examined intestinal segments. The addition of serine protease inhibitors such as a combination of aprotinin, soybean trypsin inhibitor, and Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), as well as casein profoundly improved the stability. Because we were able to improve the stability of IGF-I in vitro in all species at the same degree we speculate that a similar extension of half-life might also be possible in the human intestinal system. PMID- 11782921 TI - Development and significance of resistance to protease inhibitors in HIV-1 infected adults under triple-drug therapy in clinical practice. AB - Development of drug resistance is considered a major cause for failure of antiretroviral therapy in human immunodeficiency virus type 1 (HIV-1)-infected patients adherent to treatment. However, the rate of emergence and the significance of HIV-1 drug resistance in clinical practice have been not investigated thoroughly. Selection of HIV-1 variants that are genotypically resistant to protease inhibitors was studied in all the patients (n = 169) who completed at least 18 months of treatment with a protease inhibitor plus two nucleoside reverse transcriptase inhibitors at two urban Italian hospitals. HIV-1 carrying primary protease inhibitor resistance mutations was detected in 70 (41.4%) patients. The estimated proportion of patients developing genotypic resistance to protease inhibitors at 12 and 24 months was 18.3% (95% CI, 12.5 24.2%) and 33.9% (95% CI, 26.4-41.5%), respectively. Independent predictors of development of resistance to protease inhibitors were higher HIV-1 RNA levels at the nadir (P < 0.0001) and inclusion of ritonavir or saquinavir versus indinavir in the starting regimen (P = 0.0313). Resistance to protease inhibitors was strongly associated with a lower response to treatment, as shown by HIV-1 RNA load (P = 0.0001) and CD4 cell counts (P = 0.005). However, a linear increase in CD4 cell counts was maintained up to the end of follow-up even in the protease inhibitor-resistant population. Resistance to protease inhibitors develops in a relevant proportion of patients under long-term triple-drug therapy in clinical practice and is associated with virological treatment failure and limitation of CD4 cell increase. PMID- 11782922 TI - Molecular epidemiology of molluscum contagiosum virus and analysis of the host serum antibody response in Spanish HIV-negative patients. AB - Molluscum contagiosum virus (MCV) lesions from Spanish human immunodeficiency virus (HIV)-negative patients were clinically examined and analyzed for virus detection and typing. In a study of 147 patients, 97 (66%) were children under 10 years, of whom 49% had atopic dermatitis. MCV lesions were morphologically indistinguishable among the different age groups, but atopic patients presented larger lesions compared with patients without the disorder. In adults, lesions were observed mainly on the genitals. MCVI was the predominant subtype. The deduced MCVI/MCVII ratio (146:1) was much higher than that found in other geographical areas. Protein preparations of the virus-induced lesions were immunoblotted with sera from 25 MCVI patients. The host-serum antibody response was weak and variable, although no significant differences were found between atopic and nonatopic patients. Three immunoreactive proteins of 74/80, 60, and 35 kDa were detected in almost all the analyzed sera. The 35 and 74/80-kDa proteins were virus specific, whereas the 60-kDa protein band was composed of a mix of human keratins. Immunoblotting of MCV lesions and vaccinia virus-infected cell extracts with either MCV patient serum or a rabbit antiserum against vaccinia virus showed no cross-reactivity of these two human poxviruses at the antigenic level. PMID- 11782923 TI - Molecular epidemiology of hepatitis B virus in Amsterdam 1992-1997. AB - To gain insight into the spread of hepatitis B among various risk groups in Amsterdam a 6-year (1992-1997) retrospective DNA sequencing study was carried out on isolates from stored sera from reported primary cases of acute hepatitis B infection. Cases were classified according to risk behavior, as determined in interviews. Of the available serum, a selected region of hepatitis B-virus-DNA was amplified and sequenced. The nucleotide alignments were subjected to phylogenetic tree analysis. When nucleotide alignments were subjected to phylogenetic analysis, the strains of 54 isolates, 26% of the 204 reported primary cases, clustered in five genotypes: A, C, D, E, and F. In genotype A, a cluster related to men having sex with men was identified. In genotype D, two subclusters could be identified: one was related to injecting drug use and another was related to the Moroccan population in Amsterdam. The remaining strains showed a high genetic variability within three different genotypes: F, E, and C. Of the 14 identical isolates in the "homosexual men cluster," one was isolated from a female heterosexual. Of the 14 identical strains in the "drug users strain," six were from non-drug using heterosexual active individuals. In the cluster of twelve isolates related to hepatitis B-endemic areas, probable modes of transmission were varied. Sequence analysis provides important insight into the spread of hepatitis B among various high-risk groups. The analysis indicates that the prevention strategy in The Netherlands fails to stop transmission of hepatitis B from persistently infected individuals originating from hepatitis B endemic countries. PMID- 11782924 TI - Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen using a novel electron spin resonance technique. AB - We developed a highly sensitive enzyme immunoassay (EIA), the p-AP/HHTIO method, that detects serum hepatitis B surface antigen (HBsAg) by measuring stabilized nitroxide radicals using a novel electron spin resonance technique [Matsuo et al. (1998) Free Radic Biol Med 25:929-935]. To demonstrate the clinical significance of this method and to reveal occult hepatitis B virus (HBV) infection in patients, we used the method to analyze serum samples of 30 patients with acute or fulminant hepatitis who were negative for HBsAg by standard EIA, and those of seven chronic HBV carriers who became negative for HBsAg during a follow-up period by standard EIA. We also examined serum HBV DNA by amplification of the HBV S gene, using the polymerase chain reaction (PCR) technique. The p-AP/HHTIO method showed that 9 of 20 (45%) patients with acute hepatitis and 2 of 10 (20%) with fulminant hepatitis were positive for HBsAg; PCR detected HBV DNA in these HBsAg-positive patients. Antibody against hepatitis B core antigen was detected in one patient with fulminant hepatitis. The p-AP/HHTIO method demonstrated prolonged seropositivity of HBsAg even after standard EIA showed a loss of HBsAg in all seven HBV carriers. Our p-AP/HHTIO method is useful for screening and diagnosing HBV infection in patients with liver diseases who are negative for conventional HBV-related serological markers. PMID- 11782925 TI - Mutations in the X region and core promoter are rare and have little impact on response to interferon therapy for chronic hepatitis B. AB - Therapy for chronic hepatitis B with interferon-alpha (IFN) may result in viral clearance and hepatitis B e seroconversion in 30-40% of patients. It is still unclear whether viral genetic variability influences response rates. However, certain core promoter mutations were recently associated with a better response to IFN. In the present study, the entire X region, including the core promoter, of hepatitis B virus (HBV) from 26 HBeAg-positive patients treated with IFN for 12 weeks, was sequenced. Serum samples pre-treatment, at end-of-treatment, and at follow-up of 18 sustained and 8 nonsustained responders were analyzed. Most patients were of European origin and had moderate aminotransferase elevation (mean 2.4 x upper limit of normal) and genotype A infection. Before treatment, 16 patients had an X region identical to a consensus sequence of the corresponding genotype; in the remaining 10 patients, a median of 1.5 mutations were found. After treatment, 1-4 new mutations (mean 1.8) had emerged in 5 patients. There was no association between specific mutations, or the number of mutations, and response to IFN. The low frequency of mutations indicates that analysis of this region is of limited clinical value and that emerging mutations in this region are not major determinants of response to treatment with IFN-alpha. PMID- 11782926 TI - Hepatitis C virus infection and genotypes among human immunodeficiency virus high risk groups in Cameroon. AB - Parenteral transmission of HCV is well established but other possible routes such as heterosexual transmission are still questioned. The Central African region is characterised by a high HCV endemicity without any evidence on the route of transmission. The information on HCV genotypes that circulate in this area is also limited and controversial. HIV infection is very frequent in this region and mostly acquired via the heterosexual route. The aim of this work was to investigate the trend of HCV infection and genotypes among HIV high-risk groups from Cameroon. Four hundred eighty-two patients including 229 tuberculosis clinic attendants, 184 sexually transmitted disease clinic attendants, and 69 HIV clinical suspects from another clinic were enrolled. All plasma samples were screened for antibodies to HCV and HCV RNA. Genotypes were assigned by sequencing a 5'UTR amplified fragment. The overall prevalence of HCV markers was 11.6% and a significant increasing trend with respect to age was observed. A proportion of 64.1% (34/53) of HCV antibody positive samples was viraemic. HCV RNA was found in 3 samples that were indeterminate in RIBA 3.0. One was negative in the antibody screening test and the two others were weakly positive. The data on HCV genotypes revealed that genotype 1 was involved in 57% of viraemias, genotype 2 in 24%, while genotypes 4 and 5a accounted for 16 and 3%, respectively. In contrary to the predominance of genotype 4 reported in some African countries and even the neighbouring countries, these data demonstrate clearly that HCV infection in Cameroon is dominated by genotypes 1 and 2. No association was found between the HCV markers and the presence of HIV infection. It is concluded, therefore, that the heterosexual route plays a minor role in HCV transmission in this country. PMID- 11782927 TI - Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo. AB - Many viruses can inhibit protein synthesis in their host cells by targeting translation ("translational shutoff"). There are few reports on the effects of hepatitis C virus (HCV) infection on protein synthesis, because of the lack of a reproducible tissue culture system for HCV. In this study, the influence of seven HCV proteins (core, NS2, NS3, NS4A, NS4B, NS5A, NS5B) on protein synthesis was examined using a reporter assay. In addition, it was determined whether the HCV proteins inhibit protein synthesis via transcription or translation using an RNase protection assay and the effect of HCV proteins on translation from the HCV internal ribosome entry site (IRES) was also examined using a bicistronic reporter. Of the seven HCV proteins, NS4A and NS4B proteins inhibited cellular protein synthesis by targeting the process of translation. They also inhibited translation from the HCV IRES. Moreover, NS4A protein, induced under the control of doxycycline, inhibited the proliferation of HeLa cells. In conclusion, HCV NS4A and NS4B proteins have an effect of translational inhibition. This novel function may be involved in HCV infection and help its survival in host cells. PMID- 11782929 TI - Antibody responses against B-cell epitopes of the hypervariable region 1 of hepatitis C virus in self-limiting and chronic human hepatitis C followed-up using consensus peptides. AB - A rare collection of serum samples from patients with hepatitis C virus (HCV) infection followed up from the onset of clinical symptoms was acquired. RNA corresponding to the hypervariable region 1 (HVR1) of E2 protein of HCV isolated from nine patients was reverse-transcribed, amplified, sequenced, and HVR1 amino acid sequences were deduced. These sequences and a selection of HVR1 amino acid sequences of matching HCV genotypes from protein and translated DNA sequence databanks were used to create the HVR1 amino acid consensus. The degenerated peptides mimicking N- and C-termini of the consensus were synthesized. Most (76%) of 17 patients followed up for the period from 1 week to a minimum of 7 months from the onset of acute symptoms developed antibodies reacting with peptides representing N- and/or C- termini of HVR1. Antibody recognition of the consensus HVR1 peptides indicates that the variability of HVR1 sequence on the protein level is limited with certain conserved structure(s) being untouched. A tendency was observed for a slower development of anti-HVR1 antibody response in patients developing chronic HCV, as compared to those with self-limiting HCV infection. PMID- 11782928 TI - Mixed cryoglobulinaemia and chronic hepatitis C virus infection: the rheumatic manifestations. AB - The prevalence of rheumatologic symptoms in patients with mixed cryoglobulinaemia associated to chronic hepatitis C virus (HCV) infection was investigated. One hundred fourteen patients (96 female, mean age 63.5 years) with chronic HCV infection and cryoglobulinaemia were recruited. The presence, concentration, and type of cryoglobulins were tested by immunofixation. Rheumatoid factor (RF) and antinuclear antibody (ANA) were also measured. Rheumatological related symptoms were investigated by anamnesis and clinical evaluation. HCV genotype was determined by polymerase chain reaction (PCR) with genotype specific primer. Type II cryoglobulinaemia was identified in 39 cases and it was of type III in 58. HCV RNA genotype was determined in 62 patients: 47 (76%) were infected by genotype1b, 8 (13%) by genotype 2a, while other genotypes were less common. RF and ANA were, respectively, present in 36 (31.5 %) and 4 (3.5 %) patients at low titre (RF < 50 UI/ml, ANA < 1:80). Of the 114 patients, 51 (44.7%) complained for rheumatological symptoms. The mean cryocrit value in these patients was 2,6 %, while in patients with HCV infection, liver disease, and cryoglobulinaemia without rheumatological symptoms the cryocrit value was lower than 0.5% in 50% of cases. It is concluded that patients with chronic HCV infection reported a wide variety of rheumatological manifestations, impairing their quality of life, with discrete frequency. These results suggest that HCV infection should be considered in the differential diagnosis of rheumatological symptoms of unknown origin. PMID- 11782930 TI - Human recombinant myeloperoxidase antiviral activity on cytomegalovirus. AB - In vitro incubation of human cytomegalovirus (Towne strain) with 8 U/ml human recombinant myeloperoxidase plus sodium chloride and glucose nearly abolished viral infectivity. To assay the effect on intracellular infection, cell toxicity of the enzymes was first studied. Even the high dose of 16 U/ml of recombinant myeloperoxidase plus 10 mU/ml glucose oxidase did not decrease MRC5 cell growth. By contrast, this dose reduced proliferation of activated THP1 cells. Even half of the myeloperoxidase dose proved slightly toxic to these cells. Non-cytotoxic concentrations of the reagents were used to monitor their effect on cytomegalovirus infection. In MRC5 cells, even the low dose of 4 U/ml myeloperoxidase plus glucose oxidase inhibited synthesis of cytomegalovirus early antigens, as tested by immunofluorescence. Viral release in the supernatant was decreased by 4 logs. In THP1 cells, which produce endogenously hydrogen peroxide, myeloperoxidase alone (8 U/ml) decreased the formation of early and late antigens by 53 and 44%, respectively. PMID- 11782931 TI - Enteroviral meningitis in Northern Jordan: prevalence and association with clinical findings. AB - During the summer-autumn of 1999, 390 specimens of cerebrospinal fluid were taken from infants and children younger than 15 years of age. They were suspected of having meningitis and were admitted to Princess Rahma Hospital, Northern Jordan. They were investigated for the presence of enteroviruses using shell vial culture and indirect immunofluorescence assays. Most cases (46.9%) occurred in children younger than 1 year of age in which males represented 71.9%. The common symptoms were fever, vomiting, and headache. Enteroviruses were isolated from 32 (8.2%) cases, coxsackievirus B types 2, 4, and 5 from 15 (46.9%) cases, and echovirus 9 (31.3%) was the most common identified serotype. The virus isolation rate was directly proportional to the number of leukocytes in the cerebrospinal fluid. However, enteroviral isolation was demonstrated in 4 (12.5%) of 32 cerebrospinal fluid specimens without pleocytosis. Leukocyte differential count revealed a predominance of polymorphonuclear cells in 71.4% of the cases. Hospitalization ranged from 1 day to 25 days with a mean of 7 days. The majority of enterovirus infected patients (88.9%) were treated with at least one type of antibiotic. These results emphasize the importance of shell vial culture assay for diagnosing enteroviruses, especially in laboratories that do not have access to advanced techniques such as polymerase chain reaction. PMID- 11782932 TI - In vitro antiviral activity of dermaseptins against herpes simplex virus type 1. AB - The in vitro antiviral activity of dermaseptins (S1-S5) against herpes simplex virus type 1 (HSV1) was investigated. These peptides were incubated with the virus and its target cells under various conditions, and their effects were examined by the cytopathic effect inhibition assay or by reduction in virus yield in Hep-2 cell cultures as well as by direct immunofluorescence. Dermaseptin S4 displayed the strongest antiviral effect against HSV1, at micromolar doses. Experiments including acyclovir as a reference antiviral agent were performed to investigate the mode of action of this dermaseptin. In contrast to acyclovir, dermaseptin S4 showed its inhibitory effect only when applied to the virus before, or during virus adsorption to the target cells. This suggested that the activity of this dermaseptin was exerted at a very early stage of the viral multiplication cycle, most likely at the virus-cell interface. PMID- 11782933 TI - HHV-8 subtypes in South Africa: identification of a case suggesting a novel B variant. AB - Human herpesvirus 8 (HHV-8) has been identified as the causative agent for all forms of Kaposi's sarcoma and is also associated with the development of body cavity-based B-cell lymphomas and multicentric Castleman's disease. HHV-8 genomes are now classified into five major subtypes (A-E) that reflect sequence heterogeneity in the highly variable open reading frame (ORF) K1. To identify HHV 8 subtypes associated with different forms of Kaposi's sarcoma, we compared the ORF 26 and ORF-K1 gene sequences from South African patients with the prototype strains of the major subtypes, as well as published sequences from other African strains. DNA prepared from Kaposi's sarcoma biopsies and/or peripheral blood lymphocytes were available from 14 patients with postrenal transplant (iatrogenic) Kaposi's sarcoma, six patients with the African endemic form, and one patient with AIDS-related body cavity-based B-cell lymphoma. We identified a B2 subtype in six patients, four of whom also had a novel B5 type ORF 26 polymorphism. Two patients had B2 type patterns for both the ORF 26 and ORF-K1 genes. The ORF-K1 subtype A5 was identified in samples from three patients with a B3/C2 type polymorphism in the ORF 26 gene. A novel ORF-K1 B variant strain was identified in a patient with African endemic Kaposi's sarcoma, who also had a B3/C2 class ORF 26 pattern. In 58.3% of iatrogenic Kaposi's sarcoma patients, a B5-type ORF 26 gene sequence pattern was identified. No association was found among particular subtypes, geographical origin of patients, or clinical presentation. PMID- 11782934 TI - Epidemiological survey of neonatal non-polio enterovirus infection in the Netherlands. AB - The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1 to December 1 with a peak in the summer months. Sixty-five percent (n = 78) of neonates became ill within the first 2 weeks of life. Echoviruses and Coxsackie virus type B were isolated most frequently, in 77 (65%) and 29 (24%) infants, respectively. Diagnosis was made by viral isolation from stool, nasopharyngeal swab, cerebrospinal fluid, and blood. One hundred four (87%) infants developed fever and 25 (21%) infants had diarrhea. A clinical diagnosis of sepsis was made in 42 (35%) infants and meningitis was diagnosed in 28 (24%) cases. The great majority of sepsis cases (36/86%) occurred in infants less than 15 days of age. In conclusion, non-polio enteroviruses (especially echoviruses) are a common and underreported cause of neonatal infection in the Netherlands in the summer months and are associated with a clinical diagnosis of sepsis or meningitis cases in the first 2 weeks of life in a high proportion of cases. PMID- 11782935 TI - Baculovirus expression of erythrovirus V9 capsids and screening by ELISA: serologic cross-reactivity with erythrovirus B19. AB - Diagnosis of erythrovirus B19 (B19) relies on serology and the detection of viral DNA. Recently, a distinct erythrovirus isolate termed V9, markedly different from erythrovirus B19 (> 11% nucleotide disparity), was isolated. Standard B19 PCR assays were inconclusive and serologic tests failed to categorize V9 as an acute B19-like infection. Sequencing, combined with PCR studies, have since demonstrated the need for specific and differentiated techniques when examining samples for possible B19 or V9 viremia. The antigenic properties of the V9 capsid proteins have not been characterized previously. To address this question, V9 VP1 and VP2 open reading frames were cloned and expressed in insect cells using a baculovirus vector. Large quantities of purified recombinant V9 capsid protein were produced and electron micrographs revealed self-assembly of V9 VP1/VP2 and VP2 capsids into empty icosahedral erythrovirus-like particles with a diameter of approximately 23 nm. Screening of a panel of 270 clinical samples for the presence of V9 IgM and IgG antibodies in ELISA showed 100% serologic cross reactivity between B19 and V9 when comparing V9 VP2 capsids to a commercial B19 VP2 assay. This suggests that both a V9 and a B19 antibody response may be diagnosed equally well by ELISA using either V9 or B19 recombinant capsids as antigen source. Retrospectively, translation of the V9 sequence indicates that despite a significant genetic variation on the DNA level, the majority of the discrepant DNA sequence represents silent mutations leading to an amino acid sequence very similar to the known B19 strains (96-97% homology). PMID- 11782936 TI - HTLV-II infection associated with a chronic neurodegenerative disease: clinical and molecular analysis. AB - HTLV II is a retrovirus endemic in some Amerindian tribes and spread worldwide with a high prevalence among intravenous drug abusers. It has three different genetic subtypes a, b, and d, defined mainly by the long terminal repeat (LTR) region. HTLV II has been associated with a neurodegenerative disease in few cases. We describe the first well-documented case in Brazil where the virus is endemic in isolated ethnic groups. The patient is a 55-year-old woman with a chronic and painful syndrome characterized by spastic paraparesis, hyperactive reflexes and spastic bladder. Somatosensory evoked potential indicates a thoracic spinal cord lesion. Computer tomography showed periventricular demyelination. Enzyme-linked immunosorbent assay was positive for HTLV I/II whereas the discriminatory Western blot was indeterminate. Molecular analysis of the Tax region revealed a HTLV II pattern that was also confirmed through sequencing the LTR region. Phylogenetic analysis of the LTR sequence shows an HTLV IIa subtype that clustered with the virus isolated from Kayapo Indians and Brazilian urban intravenous drug users. Indeterminate Western blots are frequently found using commercial kits, therefore we recommend that all cases in which a myelopathy is associated with an indeterminate serological result should be evaluated by PCR to determine the actual number of HTLV II associated myelopathy cases. PMID- 11782937 TI - GB virus C and TT virus infections in Japanese patients with autoimmune hepatitis. AB - The association of the newly identified viruses, GB virus C (GBV-C) and TT virus (TTV), with autoimmune hepatitis remains to be elucidated. Sera from 20 Japanese patients with autoimmune hepatitis and 50 volunteer blood donors were assayed for GBV-C RNA, antibodies to the GBV-C second envelope protein (E2), and TTV DNA. GBV C RNA was examined by reverse-transcription polymerase chain reaction (PCR). Anti GBV-C E2 (a marker of past infection) was tested by an enzyme-linked immunosorbent assay. TTV DNA was amplified by PCR using two different sets of primers: one derived from the original N22 sequence (Set A) and the other from the untranslated region (Set B). None of the patients or controls had GBV-C RNA. Anti-GBV-C E2 was found significantly more often in patients with autoimmune hepatitis (3/20) than in controls (1/50; P = 0.034). The prevalence of TTV DNA detected by primers Set A and that detected with either Set A or B were similar among patients with autoimmune hepatitis (4/20 and 16/20, respectively) and controls (9/50 and 40/50, respectively). Clinical characteristics did not differ in association with any of these viral markers. Of the 13 TTV isolates amplified with Set A, seven were classified as genotype 1a, four as genotype 1b, and 2 as genotype 3; no particular strain was associated with autoimmune hepatitis. These findings provide no compelling evidence that GBV-C or TTV has a pathogenic role in autoimmune hepatitis. PMID- 11782938 TI - Virological and serological analysis of rhinovirus infections during the first two years of life in a cohort of children. AB - The occurrence of rhinovirus infections in a cohort of 329 children during the first 2 years of life was determined by virus detection and serological methods. Rhinovirus detection on nasopharyngeal aspirates and middle ear fluids comprised a combination of virus isolation in HeLa Ohio cells and a reverse transcription polymerase chain reaction (RT-PCR)-hybridization assay on the inoculated cell cultures. Nasopharyngeal aspirates were collected when the child was referred to the study clinic because of respiratory symptoms. Nasopharyngeal aspirates and middle ear fluids were collected after clinical diagnosis of an acute otitis media. Complement-fixing antibodies to rhinovirus were determined from scheduled serum specimens collected at 6, 12, 18, and 24 months of age and from paired sera taken in the cases of acute otitis media. Rhinovirus infections were shown to be common in infants, 24% of the children had complement-fixing antibodies at the age of 6 months and 22% had had at least one rhinovirus episode indicated by virus detection. At the age of 2 years, 91.3% of the children had rhinovirus specific antibodies, while 79% of the children had experienced rhinovirus infection as judged by the virus detection tests. However, the complement fixation assay was poor as a diagnostic test. Of 458 acute otitis media episodes studied, 41% were shown to be associated with a rhinovirus by RT-PCR hybridization, while significant fourfold rise in rhinoviral antibodies was detected only in 7% of the cases. PMID- 11782939 TI - Detection of human group C rotaviruses in Nigeria and sequence analysis of their genes encoding VP4, VP6, and VP7 proteins. AB - In a survey on the etiology of acute gastroenteritis in infants and young children in Nigeria, group C human rotaviruses were detected in two of 112 rotavirus positive stool specimens collected between 1999 and 2000. The VP7, VP6, and VP4 genes of the two Nigerian human group C rotavirus strains (Jajeri and Moduganari) were sequenced in this study. Comparative sequence analysis with other published human group C rotaviruses showed that the genes encoding the three structural proteins were remarkably conserved in primary structure with few mutations. The VP4 and VP7 genes from the two Nigerian strains were related more closely to each other than to those of other published strains, and formed a separate cluster on the phylogenetic tree. In contrast, it was of note that VP6 gene of strain Moduganari was related more closely to the Brazilian strain Belem than to the other Nigerian strain Jajeri. This is the first report of identification of human group C rotavirus in Nigeria and constitutes the first sequence data of human group C rotaviruses in the African continent. PMID- 11782940 TI - TT virus: preferential distribution in CD19(+) peripheral blood mononuclear cells and lack of viral integration. AB - In order to determine whether peripheral blood mononuclear cells (PBMC) contain proviral DNA or double-stranded replicative forms of TT virus (TTV) and to define which cell subset harbors TTV, we analyzed 126 PBMC DNA samples by PCR, using the NG059/NG061/NG063 and the T801/T935 primer sets. TTV sequences were detected in nearly 20% (25/126) of PBMC DNA samples. Analysis of PBMC subsets revealed that TTV was preferentially distributed in CD19(+) cells. TTV DNA was also detected in CD3(+)/CD19(+) double-depleted cells but was undetectable in CD3(+) cells. After degradation of single-stranded DNA using mung bean nuclease (MBN), TTV could not be detected in previously TTV-positive PBMC DNA samples nor in DNA from CD19(+) cells, CD3(+)-depleted, and CD3(+)/CD19(+) double-depleted cells, indicating the lack of TTV DNA integration and the absence of viral double-stranded replicative intermediates in PBMC or PBMC subset cells. Our data indicate that PBMC and PBMC subsets are not the major sites of TTV replication. PMID- 11782941 TI - Early acquisition of TT virus in infants: possible minor role of maternal transmission. AB - This study assessed the prevalence of TT virus (TTV) viremia in pregnant women and evaluated the role of maternal transmission in early acquisition of TTV in infants in Taiwan. Two groups of pregnant women were screened for TTV using polymerase chain reaction. The first group included 135 healthy pregnant women attending the obstetrics department for routine prenatal care and the second group from 25 GB virus-C/hepatitis G virus (GBV-C/HGV)-infected mothers. In both groups, when TTV infection was found in mothers, serial serum samples were collected for the infants at regular intervals until 1 year of age and were tested for TTV DNA. The results showed that 40% (54/135) of the women undergoing routine prenatal care and 56% (14/25) of GBV-C/HGV-infected pregnant women were positive for TTV DNA (P = 0.137). Of the 54 TTV-infected mothers in the routine prenatal group, 29 and their 30 infants received regular follow-up. The positive rate of TTV DNA in infants was 40% (12/30) in the routine prenatal group and 29% (4/14) in the group with GBV-C/HGV-infected mothers (P = 0.463). All but 2 of the 16 TTV-infected infants had normal serum alanine aminotransferase levels during follow-up. The phylogenetic analysis in 7 mother-infant pairs showed that the homology was diverse in each pair and a close genetic relatedness was found in 2 mother-infant pairs. In conclusion, TTV viremia is common in pregnant Taiwanese women and their infants. However, the results suggest that maternal transmission may play only a minor role in early acquisition of TTV in infants. PMID- 11782943 TI - Taming the fierce roller: an "enhanced" understanding of cellular differentiation in Volvox. AB - Few organisms offer a better opportunity to explore the mechanisms of cellular differentiation, and their origins, than Volvox. Volvox consists of just two cell types, germ and soma, and is the most complex member of a family of green algae that includes unicellular and multicellular relatives. At the heart of the cell fate determination program of Volvox carteri is the regA gene, which encodes a putative transcriptional repressor that prevents somatic cells from expressing reproductive functions. Stark et al. have dissected the regA gene to determine how its expression is restricted to somatic cells. Their results suggest that regA expression is controlled by multiple enhancers, the most important of which prevents transcription in reproductive cells. While these findings shed light on Volvox development, they also raise a new set of questions about the mechanisms that control the germ-soma dichotomy in this organism. PMID- 11782944 TI - Shedding light on sheddases: role in growth and development. AB - The extracellular domains of several integral membrane proteins are released from the cell surface by a group of enzymes known as "sheddases" through a process called "ectodomain shedding". Because many transmembrane growth and differentiation factors, including members of the epidermal growth factor (EGF) family that play a crucial role in development, require ectodomain shedding for proper action in vivo, proteolysis is now viewed as a regulatory mechanism in the developing embryos. Two recent reports by Zhao et al. provide evidence for the role of cell surface proteolysis by an ADAM (a disintegrin and metalloprotease) in the development of murine lung. Inhibition of tumor necrosis factor-alpha converting enzyme (TACE, ADAM17) by the hydroxamic acid-based metalloprotease inhibitor (TAPI), or a targeted mutation in Zn(2+)-binding domain of TACE, disrupts two essential epithelial functions in lung development: branching morphogenesis and cytodifferentiation. Evidence for the role of ADAMs as sheddases in development and growth factor signaling is discussed. PMID- 11782945 TI - Fat facets does a Highwire act at the synapse. AB - Neuromuscular synapses are highly dynamic structures that respond to both intercellular and intracellular cues to manipulate synaptic form. A variety of post-translational modifications of synaptic proteins are used to regulate synaptic plasticity. A recent report by DiAntonio et al. shows that two ubiquitin pathway proteins, Highwire and Fat facets, may be mutually antagonistic regulators of presynaptic growth at the Drosophila neuromuscular junction. This work adds support to the emerging idea that ubiquitin, a polypeptide that targets proteins for proteasomal degradation, regulates synaptic development. PMID- 11782946 TI - Integrin control of cell cycle: a new role for ubiquitin ligase. AB - Receptor tyrosine kinases and integrins are activated by growth factors and extracellular matrix, respectively. Their activation leads to signal transduction cascades that control many aspects of cell phenotype, including progression through the G(1) phase of the cell cycle. However, the signalling cassettes driven by growth factors and matrix do not work independently of each other. Integrin triggering is essential to facilitate kinase- and GTPase-mediated signals and thereby drive efficient transfer of information through the growth factor-cyclin axis. A recent study indicates that an additional type of player has a key role in adhesion-regulated control of cell cycle, namely ubiquitin ligase. PMID- 11782947 TI - Growth, hedgehog and the price of GAS. AB - Embryonic development in a given species is orchestrated by genes regulating growth and differentiation in a stereotyped and conserved manner, resulting in embryos of consistent size and shape. Several signaling pathways, including that of Sonic Hedgehog (SHH), have been implicated in these processes. Recent experiments with Gas1 indicate that it may act as a growth-inducing gene, challenging its previous function as a gene specifically involved in growth arrest. Moreover, GAS1, a GPI-linked membrane protein, can bind SHH, suggesting an interacting link between growth and patterning through SHH and GAS1. PMID- 11782948 TI - Coordination of cell proliferation and cell fate decisions in the angiosperm shoot apical meristem. AB - A unique feature of flowering plants is their ability to produce organs continuously, for hundreds of years in some species, from actively growing tips called apical meristems. All plants possess at least one form of apical meristem, whose cells are functionally analogous to animal stem cells because they can generate specialized organs and tissues. The shoot apical meristem of angiosperm plants acts as a continuous source of pluripotent stem cells, whose descendents become incorporated into organ primordia and acquire different fates. Recent studies are unveiling some of the molecular pathways that specify stem cell fate in the center of the shoot apical meristem, that confer organ founder cell fate on the periphery, and that connect meristem patterning elements with events at the cellular level. The results are providing important insights into the mechanisms through which shoot apical meristems integrate cell fate decisions with cellular proliferation and global regulation of growth and development. PMID- 11782949 TI - Cell proliferation and growth in C. elegans. AB - The cell division and differentiation events that occur during the development of the nematode Caenorhabditis elegans are nearly identical between different individuals, a feature that distinguishes this organism from larger and more complex metazoans, such as humans and Drosophila. In view of this discrepancy, it might be expected that the regulation of cell growth, division and differentiation in C. elegans would involve mechanisms separate from those utilized in larger animals. However, the results of recent genetic, molecular and cellular studies indicate that C. elegans employs an arsenal of developmental regulatory mechanisms quite similar to those wielded by its arthropod and vertebrate relatives. Thus, the nematode system is providing both novel and complementary insights into the general problem of how growth and patterning events are integrated in development. This review offers a general perspective on the regulation of cell division and growth in C. elegans, emphasizing recent studies of these crucial aspects of development. PMID- 11782950 TI - Control of growth and organ size in Drosophila. AB - Transplantation experiments have shown that developing metazoan organs carry intrinsic information about their size and shape. Organ and body size are also sensitive to extrinsic cues provided by the environment, such as the availability of nutrients. The genetic and molecular pathways that contribute to animal size and shape are numerous, yet how they cooperate to control growth is mysterious. The recent identification and characterization of several mutations affecting growth in Drosophila melanogaster promises to provide insights. Many of these mutations affect the extrinsic control of animal size; others affect the organ intrinsic control of pattern and size. In this review, we summarize the characteristics of some of these mutations and their roles in growth and size control. In addition, we speculate about possible connections between the extrinsic and intrinsic pathways controlling growth and pattern. PMID- 11782951 TI - Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. AB - It has generally been observed that cells grow to a certain size before they divide. In the last few years, the PI3K signal transduction pathway has emerged as one of the main signaling routes utilized by cells to control their increase in size. Here we focus on two components of this pathway, PKB and S6K, and briefly review the experiments that initially uncovered their roles in cell size control. In addition, we discuss a number of recent observations suggesting that the generic models used to describe this pathway to date may have been oversimplified. Indeed, recent observations in Drosophila and mouse support a more complex interaction between these signaling components in development. Finally, we have utilized two contemporary studies involving PKB- and S6K deficient mice as a paradigm to underscore the importance of cell size and to accurately delineate the connections between signaling pathways for human disease, such as diabetes mellitus. PMID- 11782952 TI - Growth and death in the developing mammalian kidney: signals, receptors and conversations. AB - Because the kidney (metanephros) starts to function before completing development, its patterning and morphogenesis need to be closely integrated with its growth. This is achieved by blast cells at the kidney periphery generating new nephrons that link up to the extending collecting-duct arborisation, while earlier-formed and more internal nephrons are maturing and beginning to filter serum. This pattern of development requires that cell division and apoptosis be co-ordinated in the various kidney compartments (collecting-ducts, blast cells, metanephric mesenchyme, nephrons and vascular system). The underlying regulatory networks for cell proliferation are beginning to be unravelled, mainly through expression studies, mutation analysis and experimentation in vitro. This article summarises current knowledge of kidney growth and apoptosis, and analyses some of the 80 or so ligand-receptor pairings that seem to sustain development and growth. It also points to some unanswered questions, the most intriguing being what role does apoptosis play during normal kidney development? PMID- 11782953 TI - Derangement of growth and differentiation control in oncogenesis. AB - Human neoplasms develop following the progressive accumulation of genetic and epigenetic alterations to oncogenes and tumor suppressor genes. These alterations confer a growth advantage to the cancer cell, leading to its clonal proliferation, invasion into surrounding tissues, and spread to distant organs. Genes that are altered in neoplasia affect three major biologic pathways that normally regulate cell growth and tissue homeostasis: the cell cycle, apoptosis, and differentiation. While each of these pathways can be defined by a unique set of molecular events, they are not biologically separate. Rather, they function more as an integrated molecular network, and perturbations in one pathway can have profound consequences on another. Insights into what distinguishes the regulation of growth and differentiation in a normal cell versus a cancer cell have led to the development of novel anticancer therapies. PMID- 11782954 TI - The intestinal epithelial stem cell. AB - This article considers the role of the adult epithelial stem cell, with particular reference to the intestinal epithelial stem cell. Although the potential of adult stem cells has been revealed in a number of recent publications, the organization and control of the stem cell hierarchy in epithelial tissues is still not fully understood. The intestinal epithelium is an excellent model in which to study such hierarchies, having a distinctive polarity and high rate of cell proliferation and migration. Studies on the small intestinal crypt provide insight into the characteristics of the stem cells in normal and regenerating circumstances and demonstrate why a thorough understanding of these cells is an essential pre-requisite for stem cell based therapeutic approaches. PMID- 11782955 TI - Report on the 17(th) European Drosophila research conference. PMID- 11782956 TI - Activators antagonize heterochromatic silencing: reply to Eissenberg. PMID- 11782957 TI - Pharmacodynamics of citicoline relevant to the treatment of glaucoma. AB - Citicoline (exogenous CDP-choline) is a nontoxic and well-tolerated drug used in pharmacotherapy of brain insufficiency and some other neurological disorders, such as stroke, brain trauma, and Parkinson's disease. A few reports indicate that citicoline treatment may also be beneficial in glaucoma. Currently glaucoma is considered a neurodegenerative disease in which retinal ganglion cells (RGC) slowly die, likely in the apoptotic mechanism. Endogenous CDP-choline is a natural precursor of cellular synthesis of phospholipids, mainly phosphatydylcholine (PtdCho). Enhancement of PtdCho synthesis may counteract neuronal apoptosis and provide neuroprotection. Citicoline, when administered, undergoes a quick transformation to cytidine and choline, which are believed to enter brain cells separately and provide neuroprotection by enhancing PtdCho synthesis; similar effect may be expected to occur in glaucomatous RGC. Furthermore, citicoline stimulates some brain neurotransmitter systems, including the dopaminergic system, and dopamine is known as a major neurotransmitter in retina and postretinal visual pathways. In a double-blind, placebo-controlled study, treatment of glaucoma resulted in functional improvement in the visual system noted with electrophysiological methods. Development of citicoline as a treatment for glaucoma is indicated. PMID- 11782958 TI - Light-induced changes in glutamate release from isolated rat retina is regulated by cyclic guanosine monophosphate. AB - Isolated rat retina was preloaded with [(14)C]glutamate and subsequently superfused to follow release of glutamate (Glu). After 20 min of superfusion in the dark, exposure of the [(14)C]Glu preloaded rat retina to a single train of white light pulses reduced Glu efflux significantly in the absence as well as in the presence of low (4 microM) and high (0.5 mM) concentrations of the Glu uptake inhibitor trans-L-pyrrolidine-2,4-dicarboxylate (t-PDC). The dark-light response was the highest in the presence of 4 microM t-PDC by establishing a plateau at 75% +/- 7% of the tonic Glu release in the dark (100%). Displaying transient to saturating responses with increasing relative luminance, time series of four trains of white light pulses arrived at a plateau of 85% +/- 10%. The cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor Zaprinast (200 microM) antagonized the effect of the light series, leading to a plateau of 115% +/- 9%. Exposure of the retina to the guanylyl cyclase inhibitor LY83583 (30 and 100 microM) showed fast, transient responses characterized by peaks at 90% +/- 1% and 80% +/- 3%, respectively. PMID- 11782959 TI - Osteopontin: a novel axon-regulated Schwann cell gene. AB - Osteopontin (OPN) is a RGD-containing glycoprotein with cytokine-like, chemotactic, and pro-adhesive properties. During wound healing, OPN is abundantly expressed by infiltrating macrophages and has been implicated in posttraumatic tissue repair. To delineate a role in the regenerative response to axotomy we examined the expression of OPN in Wallerian degeneration of the sciatic nerve in rats. Unexpectedly, we found high constitutive expression of OPN by myelinating Schwann cells (SCs) in uninjured control nerves. OPN mRNA expression was confirmed in primary cultures of rat SCs. Upon axotomy, SC-expressed OPN in the degenerating distal nerve stump transiently increased during the first days after injury, but was continuously downregulated thereafter, reaching its minimum at Day 14. Macrophages invading axotomized nerves were OPN-negative. During late stages after axotomy, SC-OPN was reexpressed in regenerating but not permanently transected nerves. We also found OPN expression by myelinating SCs in human sural nerves with a dramatic reduction in severe axonal polyneuropathies. Taken together, our study identifies OPN as a novel Schwann cell gene regulated by axon derived signals. The lack of OPN induction in infiltrating macrophages indicates fundamental differences in tissue repair between axonal injury in the peripheral nervous system and structural lesions in other organ systems. PMID- 11782960 TI - Impaired sensory function in heterozygous P0 knockout mice is associated with nodal changes in sensory nerves. AB - Mice heterozygously deficient in the major myelin component P0 are an established model of an inherited neuropathy and show signs of myelin degeneration in motor nerves. Unlike the case in patients, the sensory nerves are only mildly affected in the mouse mutants and do not show features indicative of myelin degeneration. Unexpectedly, by applying established behavioral tests, we found sensory deficits, as reflected by raised withdrawal thresholds to mechanical and thermal stimuli, whereas behavioral signs of a painful neuropathy were not detectable. By electron microscopy of longitudinal sections of sensory nerves, we found abnormalities in nodes of Ranvier comprising enlarged nodal gaps and poorly developed nodal Schwann cell microvilli. These alterations might be causally linked to the sensory deficits in the absence of profound myelin degeneration in the sensory nerves of the mutants. PMID- 11782961 TI - Recovery of adult oligodendrocytes is preceded by a "lag period" accompanied by upregulation of transcription factors expressed in developing young cells. AB - Cell cultures prepared from oligodendrocytes directly obtained from adult rat brain are composed of mature cells that lose their cell processes and myelin membrane during their isolation and therefore represent a very useful model to investigate the factors that could stimulate their recovery. We have observed that mature oligodendrocytes isolated from adult animals remain as round cells that lack processes for the first 3-4 days in culture. At the end of this lag period, however, the majority of the adult oligodendrocytes show a remarkable recovery, rapidly growing complex and extensive cell processes. Interestingly, the end of this lag period is accompanied by a dramatic upregulation in the expression of thyroid hormone (T(3)) receptor (TR). The functional importance of this increase in TR levels is supported by the observation that the majority of the cells cultured in the presence of T(3) show significantly more extensive and complex process outgrowth than the control cells in cultures lacking this hormone. In addition, this reactivation of the adult cells was also preceded by an increased expression of glucocorticoid receptor (GR) and cyclic AMP-response element binding protein (CREB), two transcription factors that together with TR appear to play important roles in the control of neonatal oligodendrocyte development. Thus, it is possible to hypothesize that upregulation of these proteins may be part of the metabolic changes that occur during the lag period required for recovery of the adult oligodendrocytes. These observations raise the question of whether these transcription factors may play any significant role during remyelination after demyelinating lesions of adult CNS. PMID- 11782962 TI - Differential regulation of myelin phagocytosis by macrophages/microglia, involvement of target myelin, Fc receptors and activation by intravenous immunoglobulins. AB - Macrophages/microglia are the key effector cells in myelin removal. Differences exist in the amount and time course of myelin uptake in the central (CNS) and peripheral nervous system (PNS), the basis of this difference, however, is not yet clarified. In the present experiments we studied the phagocytosis rate of CNS or PNS myelin by macrophages and microglia in vitro. Additionally, the effects of intravenous immunoglobulins (IVIg) on this process were investigated. In the PNS experiments, sciatic nerves were cocultured with peritoneal macrophages. Optic nerve fragments were used to characterize the myelin-removing properties of microglia. Cocultures with peritoneal macrophages aimed at investigating the differences in phagocytosis between resident microglia and added macrophages. The myelin phagocytosis in sciatic nerve fragments was higher than in optic nerves, indicating differences in the myelin uptake rate between peripheral macrophages and microglia. IVIg increased the phagocytosis of PNS myelin by macrophages, but not by microglia in optic nerves. The addition of peritoneal macrophages to optic nerve fragments did not lead to an increase in the phagocytosis of CNS myelin either. The IVIg induced phagocytosis of PNS myelin by peripheral macrophages was associated with an increased expression of macrophage Fc receptors measured by FACS. Blocking of Fc receptors by anti-Fc receptor antibody reduced the IVIg induced PNS myelin phagocytosis to basic levels, indicating that the induced but not the basic myelin uptake by macrophages is Fc receptor dependent. In contrast to peripheral macrophages, IVIg did not increase Fc receptor density on microglia. These data indicate that phagocytosis of PNS and CNS myelin by macrophages or microglia is differentially regulated. Local factors within the CNS or PNS may affect this process by modulating the surface receptor profile and activation state of the phagocytic cell or the structure of the myelin sheath. PMID- 11782963 TI - Beneficial effect of modified peptide inhibitor of alpha4 integrins on experimental allergic encephalomyelitis in Lewis rats. AB - An important event in the pathogenesis of the autoimmune disease multiple sclerosis (MS) is the recruitment of lymphocytes and inflammatory macrophages to the central nervous system (CNS). Recruitment requires adhesive interactions between the leukocytes and the microvascular endothelium, perivascular cells, and astrocytes in the CNS parenchyma. Previous studies using an animal model of MS, experimental allergic encephalomyelitis (EAE), have shown the involvement of the alpha4 integrin VLA-4 (beta4beta1). In the present study, the effect of a modified peptide inhibitor of alpha4 integrins on the clinical course and leukocyte infiltration during EAE is investigated. EAE was either induced actively, by immunizing Lewis rats with whole guinea pig MBP, or passively, by transfer of an MBP-specific T cell line. Treatment with the inhibitor (CS1 ligand mimic) completely prevented both clinical signs and cellular infiltration in passively induced EAE. Peptide treatment of actively induced EAE, which has a more severe disease course than the transfer model, significantly reduced clinical signs although the recruitment of inflammatory cells and induction of MHC class II expression was not prevented. The alpha4 inhibitor did inhibit the adhesion of lymphocytes to primary astrocytes in vitro suggesting a role for astrocyte-leukocyte interactions in the pathogenesis of induced EAE. Astrocytes were found to express an extracellular matrix protein distinct from fibronectin, which shows immune cross-reactivity with the CS1 domain of fibronectin. Our results show that small-molecule inhibitors of alpha4 integrins act therapeutically in EAE possibly by interfering with cell adhesion events involved in this autoimmune disease. PMID- 11782964 TI - Astrocytic and microglia cells reactivity induced by neonatal administration of glutamate in cerebral cortex of the adult rats. AB - Recent studies confirm that astrocytes and neurons are associated with the synaptic transmission, particularly with the regulation of glutamate (Glu) levels. Therefore, they have the capacity to modulate the Glu released from neurons into the extracellular space. It has also been demonstrated an intense astrocytic and microglia response to physical or chemical lesions of the central nervous system. However, the persistence of the response of the glial cells in adult brain had not been previously reported, after the excitotoxic damage caused by neonatal dosage of monosodium glutamate (MSG) to newborn rats. In this study, 4 mg/g body weight of MSG were administered to newborn rats at 1, 3, 5, and 7 days after birth, at the age of 60 days the astrocytes and the microglia cells were analyzed with immunohistochemical methods in the fronto-parietal cortex. Double labeling to glial fibrillary acidic protein (GFAP) and BrdU, or isolectin B(4) and BrdU identified astrocytes or microglia cells that proliferated; immunoblotting and immunoreactivity to vimentin served for assess immaturity of astrocytic intermediate filaments. The results show that the neonatal administration of MSG-induced reactivity of astrocytes and microglia cells in the fronto-parietal cortex, which was characterized by hyperplasia; an increased number of astrocytes and microglia cells that proliferated, hypertrophy; increased complexity of the cytoplasm extension of both glial cells and expression of RNAm to vimentin, with the presence of vimentin-positive astrocytes. This glial response to neuroexcitotoxic stimulus of Glu on the immature brain, which persisted to adulthood, suggests that the neurotransmitter Glu could trigger neuro-degenerative illnesses. PMID- 11782965 TI - Lack of prion protein expression results in a neuronal phenotype sensitive to stress. AB - The prion protein is a highly conserved glycoprotein expressed most highly in the synapse. Evidence has recently been put forward to suggest that the prion protein is an antioxidant. However, the functional importance of the prion protein has been disputed; it is claimed that mice genetically ablated to lack prion protein expression are normal and have no specific phenotype. We have reexamined the phenotype of prion protein knockout mice and found that there are multiple biochemical changes in the mice, including increased levels of nuclear factor NF kappaB and Mn superoxide dismutase, COX-IV decreased levels of Cu/Zn superoxide dismutase activity, decreased p53, and altered melatonin levels. Additionally, cultured cells from these mice are more sensitive to a range of insults, all linked to increased neuronal sensitivity to oxidative stress. These results imply that prion protein knockout mice are more sensitive to oxidative stress and have an altered phenotype that must be taken into account when considering the additional effects of increased levels of proteins such as Doppel. The implication of these results is that the consequence of genetic ablation of genes must include biochemical analysis as well as analyses of possible developmental and behavioral changes. PMID- 11782966 TI - Analysis of gene expression in the rat hippocampus using Real Time PCR reveals high inter-individual variation in mRNA expression levels. AB - In mammals, gene transcription is a step subjected to tight regulation mechanisms. In fact, changes in mRNA levels in the central nervous system (CNS) can account for numerous phenotypic differences in brain function. We performed a high-resolution analysis of mRNA expression levels for 37 genes selected from a normal rat hippocampus cDNA library. mRNA amounts were quantified using a Real Time PCR SYBR Green assay. We found that, in general, individuals from an inbred rat population (n = 20) have shown 2-3 times differences in the basal level of expression of the genes analyzed. Up to several fold differences among individuals were observed for certain genes. These inter-individual differences were obtained after correction for the different amounts of mRNA in each sample. Power calculations were performed to determine the number of individuals required to detect reliable differences in expression levels between a control and an experimental group. These data indicated that, depending on the variability of the candidate gene selected, it was necessary to analyze from five to 135 individuals in each group to detect differences of 50% in the levels of mRNA expression between two groups investigated. The comparison of mRNA abundance from different genes revealed a wide range of expression levels for the 37 genes, showing a 26,000-fold difference between the highest and lowest expressed gene. PMID- 11782967 TI - Constitutive overexpression of the basic helix-loop-helix Nex1/MATH-2 transcription factor promotes neuronal differentiation of PC12 cells and neurite regeneration. AB - Elucidation of the intricate transcriptional pathways leading to neural differentiation and the establishment of neuronal identity is critical to the understanding and design of therapeutic approaches. Among the important players, the basic helix-loop-helix (bHLH) transcription factors have been found to be pivotal regulators of neurogenesis. In this study, we investigate the role of the bHLH differentiation factor Nex1/MATH-2 in conjunction with the nerve growth factor (NGF) signaling pathway using the rat phenochromocytoma PC12 cell line. We report that the expression of Nex1 protein is induced after 5 hr of NGF treatment and reaches maximal levels at 24 hr, when very few PC12 cells have begun extending neurites and ceased cell division. Furthermore, our study demonstrates that Nex1 has the ability to trigger neuronal differentiation of PC12 cells in the absence of neurotrophic factor. We show that Nex1 plays an important role in neurite outgrowth and has the capacity to regenerate neurite outgrowth in the absence of NGF. These results are corroborated by the fact that Nex1 targets a repertoire of distinct types of genes associated with neuronal differentiation, such as GAP-43, betaIII-tubulin, and NeuroD. In addition, our findings show that Nex1 up-regulates the expression of the mitotic inhibitor p21(WAF1), thus linking neuronal differentiation to cell cycle withdrawal. Finally, our studies show that overexpression of a Nex1 mutant has the ability to block the execution of NGF induced differentiation program, suggesting that Nex1 may be an important effector of the NGF signaling pathway. PMID- 11782968 TI - Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation. AB - After target ablation by olfactory bulbectomy (OBX), the murine olfactory epithelium (OE) undergoes degenerative changes leading to apoptosis of olfactory receptor neurons (ORNs) followed by regenerative changes that include proliferation of progenitor cells leading to neurogenesis and ORN replacement. Macrophages recruited to the OE after OBX are involved in both the degenerative and regenerative processes. Relative quantitative RT-PCR was used to demonstrate that within hours of OBX, mRNAs encoding three key components in the leukemia inhibitory factor (LIF) signaling pathway, including LIF, LIF receptor (LIFR), and STAT3, as well as cyclin D1, a growth factor sensor indicative of progenitor cell transformation, were upregulated. These mRNAs reached peak levels of expression on or before day 3 post-OBX, coincident with the peak time for macrophage recruitment and progenitor cell proliferation. Cells expressing LIF mRNA in the OE of mice at 3 days post-OBX, the time point at which LIF mRNA expression peaked, were identified using non-isotopic in situ hybridization. LIF mRNA was localized in infiltrating macrophages; near-adjacent sections exhibited macrophages immunoreactive for F4/80, a marker for activated macrophages, in numbers commensurate with those expressing LIF mRNA. LIF mRNA was also localized in surviving ORNs, identified by their expression of olfactory marker protein (OMP) mRNA and protein in near-adjacent sections. Our data suggest that LIF functions as a mitogen originating from recruited macrophages through an intercellular signaling pathway that stimulates proliferation of progenitor cells leading to neurogenesis and regeneration, and as an intracellular survival factor for traumatized ORNs. PMID- 11782969 TI - Effects of IL-1beta, IL-6 or LIF on rat sensory neurons co-cultured with fibroblast-like cells. AB - Inflammation may affect the local presence of sensory nerve fibers in situ and inflammatory mediators influence sensory neurons in vitro. In the present study we have investigated effects of the cytokines interleukin-1beta (IL-1beta, interleukin-6 (IL-6), and leukemia inhibitory factor (LIF) on survival of and neurite growth from neonatal rat sensory neurons co-cultured with fibroblast-like cells prepared from neonatal rat skin (sFLCs) or perichondrium (pFLCs). The results showed that both FLC types expressed receptors for all three cytokines. Five ng/ml of either cytokine, but not lower or higher concentrations, supported survival of DRG neurons co-cultured with sFLCs. Neuronal survival was also enhanced by addition of the soluble IL-6 receptor (rsIL-6R) with or without IL-6. In co-cultures with pFLCs neuronal survival was promoted by IL-6, increasing with cytokine concentration. Addition of rsIL-6R without IL-6 did also stimulate neuronal survival. The growth of neurites from DRG neurons co-cultured with sFLCs was stimulated by 0.5 ng/ml LIF, unaffected by 5 ng/ml LIF and inhibited by 50 ng/ml LIF. Considering DRG neurons co-cultured with pFLCs, 50 ng/ml of either of the three cytokines, as well as rsIL-6R conditioned medium, stimulated neurite outgrowth. Some of the cytokine effects observed were reduced by application of antibodies against nerve growth factor (NGF). We conclude that that the cytokines examined affect DRG neurons in terms of survival or neuritogenesis, that the effects are influenced by cytokine concentration and the origin of the FLCs and that some of the effects are indirect, probably being mediated by factors released from FLCs. PMID- 11782970 TI - Tumor necrosis factor expressed by primary hippocampal neurons and SH-SY5Y cells is regulated by alpha(2)-adrenergic receptor activation. AB - Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA) differentiated SH-SY5Y cells were examined. Intracellular levels of TNF mRNA accumulation, as well as TNF protein and that released into the supernatant were quantified by in situ hybridization, immunocytochemistry and bioanalysis, respectively. Both neuron cultures demonstrated constitutive production of TNF. Activation of the alpha(2)-adrenergic receptor increased intracellular levels of TNF mRNA and protein in SH-SY5Y cells after addition of graded concentrations of the selective agonist, Brimonidine (UK-14304) to parallel cultures. Intracellular levels of mRNA were increased in a concentration-dependent fashion within 15 min of UK-14304 addition and were sustained during 24 hr of receptor activation. In addition, the levels of TNF in the supernatant were increased in both types of neuron cultures within 15 min of alpha(2)-adrenergic receptor activation. Furthermore, levels of TNF significantly increased in the supernatants of both neuron cultures after potassium-induced depolarization. A reduction in this depolarization-induced release occurred in hippocampal neuron cultures after exposure to the sympathomimetic tyramine with media replacement to deplete endogenous catecholamines. This finding reveals a role for endogenous catecholamines in the regulation of TNF production. Potassium-induced depolarization resulted in the release of TNF in hippocampal neuron cultures within 15 min but not until 24 hr in SH-SY5Y cultures demonstrating a temporally mediated event dependent upon cell type. Neuron expression of TNF, regulated by alpha(2)-adrenergic receptor activation demonstrates not only how a neuron controls its own production of this pleiotropic cytokine, but also displays a normal role for neurons in directing the many functions of TNF. PMID- 11782971 TI - Dual mechanisms of Ca(2+) increases elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons. AB - Cortical primary cultures were loaded with the fluorescent indicator fluo-3 for assessment of intracellular-free Ca(2+) ions with the aid of a confocal laser scanning microscope. The addition of N-methyl-D-aspartic acid (NMDA) markedly increased the number of fluorescent cells in a manner sensitive to prevention by both an NMDA channel blocker and MgCl(2). In the absence of added MgCl(2), NMDA induced a sustained increase in the number of fluorescent cells with a transient increase by KCl in cells cultured for 3 days in vitro (DIV). Both nifedipine and dantrolene were more potent in preventing the increase by NMDA in cortical preparations cultured for 9 DIV than those for 3 DIV. These results suggest that activation of NMDA receptors may lead to a sustained increase in intracellular free Ca(2+) concentrations in immature cultured neurons, in a manner less dependent on the influx through L-type voltage-dependent channels as well as the release from intracellular stores than in mature neurons. PMID- 11782973 TI - Reporting clinical trials: full access to all the data. PMID- 11782975 TI - Parkinson's genetics: an embarrassment of riches. PMID- 11782976 TI - Is the therapeutic application of neurotrophic factors dead? PMID- 11782978 TI - Thrombolysis in stroke beyond three hours: Targeting patients with diffusion and perfusion MRI. PMID- 11782979 TI - PARK6-linked parkinsonism occurs in several European families. AB - The Parkin gene on 6q25.2-27 is responsible for about 50% of autosomal recessive juvenile parkinsonism and less than 20% of sporadic early-onset cases. We recently mapped a novel locus for early-onset parkinsonism (PARK6) on chromosome 1p35-p36 in a large family from Sicily. We now confirm linkage to PARK6 in eight additional families with Parkin-negative autosomal recessive juvenile parkinsonism from four different European countries. The maximum cumulative pairwise LOD score was 5.39 for marker D1S478. Multipoint linkage analysis gave the highest cumulative LOD score of 6.29 for marker D1S478. Haplotype construction and determination of the smallest region of homozygosity in one consanguineous family has reduced the candidate interval to a 9cM region between markers D1S483 and D1S2674. No common haplotype could be detected, excluding a common founder effect. These families share some clinical features with the phenotype reported for European Parkin-positive cases, with a wide range of ages at onset (up to 68 yrs) and slow progression. However, features typical of autosomal recessive juvenile parkinsonism, including dystonia at onset and sleep benefit, were not observed in PARK6-linked families, thus making the clinical presentation of late-onset cases indistinguishable from idiopathic Parkinson's disease. PARK6 appears to be an important locus for early-onset parkinsonism in European Parkin-negative patients. PMID- 11782980 TI - In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus mediated gene transfer of neurotrophin-3. AB - Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation with a replication-incompetent, genomic herpes simplex virus-based vector containing the coding sequence for neurotrophin-3 to transduce sensory neurons of the rat dorsal root ganglion in vivo, and found that expression of neurotrophin-3 from the vector protected peripheral sensory axons from neuropathy induced by intoxication with pyridoxine assessed by electrophysiological (foot sensory response amplitude, and conduction velocity, and H-wave), histological (nerve morphology and morphometry), and behavioral measures of proprioceptive function. In vivo gene transfer using herpes simplex virus vectors provides a unique option for treatment of diseases of the sensory peripheral nervous system. PMID- 11782981 TI - Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke. AB - Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute brain ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of > or = 7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy. PMID- 11782982 TI - Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy. AB - A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during exercise. We investigated whether aerobic forearm exercise would result in an abnormal increase in venous effluent O(2) in patients with impaired skeletal muscle oxidative phosphorylation attributable to mitochondrial disease. We monitored the partial pressure of O(2) (PO(2)) in cubital venous blood at rest, during handgrip exercise, and during recovery in 13 patients with mitochondrial myopathy and exercise intolerance and in 13 healthy control and 11 patient control subjects. Resting and recovery venous effluent PO(2) were similar in all subjects, but during exercise venous PO(2) paradoxically rose in mitochondrial myopathy patients from 27.2 +/- 4.0mmHg to 38.2 +/- 13.3mmHg, whereas PO(2) fell from 27.2 +/- 4.2mmHg to 24.2 +/- 2.7mmHg in healthy subjects and from 27.4 +/- 9.5mmHg to 22.2 +/- 5.2mmHg in patient controls. The range of elevated venous PO(2) during forearm exercise in mitochondrial myopathy patients (32 to 82mmHg) correlated closely with the severity of oxidative impairment as assessed during cycle exercise. We conclude that measurement of venous PO(2) during aerobic forearm exercise provides an easily performed screening test that sensitively detects impaired O(2) use and accurately assesses the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance. PMID- 11782983 TI - Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. AB - We evaluated a kindred with X-linked mental retardation and epilepsy. Seven affected males with mild to moderate mental retardation developed seizures (primarily generalized, tonic-clonic, and atonic) that began on average at 6.8 months of age (range, 4 to 14 months). These patients did not have a history of infantile spasms. There were no dysmorphic features. Other than mental retardation, the neurological examination was unremarkable, with exception of 2 affected subjects who had mild generalized rigidity and ataxia. We identified tight linkage to a group of markers on Xp21.1-p11.4. A maximum two-point LOD score of +3.83 at straight theta = 0 was obtained for markers DXS8090, DXS1069, DXS8102, and DXS8085. This locus spans 7.7cM between DXS1049 and DXS8054 and does not overlap the locus for X-linked West syndrome. The tetraspanin gene, implicated in nonspecific mental retardation, is mapped to this region. We sequenced the tetraspanin coding sequence in subjects with X-linked mental retardation and epilepsy and did not identify disease-specific mutations. The syndrome we describe, designated X-linked mental retardation and epilepsy, is clinically and genetically distinct from X-linked West syndrome and other X linked mental retardation-epilepsy syndromes. PMID- 11782984 TI - N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve. AB - Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells. PMID- 11782985 TI - Modulation of use-dependent plasticity by d-amphetamine. AB - Use-dependent plasticity, thought to contribute to functional recovery after brain injury, is elicited by motor training. The purpose of this study was to determine if administration of d-amphetamine facilitates the effects of motor training on use-dependent plasticity. Healthy human volunteers underwent a training period of voluntary thumb movements under the effects of placebo or d amphetamine in different sessions in a randomized double-blind, counterbalanced design. Previous work in a drug-naive condition showed that such training causes changes in the direction of thumb movements evoked by transcranial magnetic stimulation and in transcranial magnetic stimulation-evoked electromyographic responses. The endpoint measure of the study was the magnitude of training induced changes in transcranial magnetic stimulation-evoked kinematic and electromyographic responses in the d-amphetamine and in the placebo conditions. Motor training resulted in increased magnitude, faster development and longer lasting duration of use-dependent plasticity under d-amphetamine compared to the placebo session. These results document a facilitatory effect of d-amphetamine on use-dependent plasticity, a possible mechanism mediating the beneficial effect of this drug on functional recovery after cortical lesions. PMID- 11782986 TI - Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve. AB - Regeneration in the peripheral nervous system is often incomplete though it is uncertain which factors, such as the type and extent of the injury or the method or timing of repair, determine the degree of functional recovery. Serial electrophysiological techniques were used to follow recovery from median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time to earliest muscle reinnervation) on the final recovery of the outcome measures. Nerve gap distance and the repair type, individually and concertedly, strongly influenced the time to earliest muscle reinnervation, and only time to reinnervation was significant when all three variables were included as outcome predictors. Thus, nerve gap distance and repair type exert their influence through time to muscle reinnervation. These findings emphasize that factors that control early axonal outgrowth influence the final level of recovery attained years later. They also highlight that a time window exists within which axons must grow through the distal nerve stump in order for recovery after nerve lesions to be optimal. Future work should focus on interventions that may accelerate the growth of axons from the lesion site into the distal nerve stump. PMID- 11782988 TI - Impaired brain GABA in focal dystonia. AB - Patients with task-specific dystonia (writer's cramp) have impaired cortical inhibition likely arising from striatal dysfunction. However, the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brains of these patients are not known. In this study, we evaluated 7 patients with right-sided focal, task-specific dystonia and 17 normal control subjects. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy revealed that brain GABA levels are decreased in specific brain regions of the focal dystonia patients compared to normal controls. A significant decrease in GABA level was observed in the sensorimotor cortex and lentiform nuclei contralateral to the affected hand, while there was only a small nonsignificant decrease in the ipsilateral sensorimotor cortex and lentiform nuclei. GABA changes in the posterior occipital region of patients were not significant. The impaired cortical GABA level correlates with prior physiologic studies showing reduced intracortical inhibition. Reduced GABA in the striatum is consistent with striatal dysfunction since GABA is a principal neurotransmitter in that region. The reduction of brain GABA in dystonia patients may explain the clinical symptomatology of focal dystonia. Magnetic resonance spectroscopy may be a useful noninvasive tool in the evaluation of regional brain GABA changes and in monitoring the effects of various therapies. PMID- 11782987 TI - Melatoninergic neuroprotection of the murine periventricular white matter against neonatal excitotoxic challenge. AB - Periventricular leukomalacia is one of the main causes of cerebral palsy. Perinatal white matter lesions associated with cerebral palsy appears to involve glutamate excitotoxicity and excess free radical production. When injected intracerebrally into newborn mice, the glutamatergic analog ibotenate induces white matter cysts mimicking human periventricular leukomalacia. Melatonin acts on specific receptors. It also exhibits intrinsic free radical scavenging properties. The goal of the present study is to determine whether melatonin can protect against excitotoxic lesions induced by ibotenate in newborn mice. Mice that received intraperitoneal melatonin had an 82% reduction in size of ibotenate induced white matter cysts when compared with controls. Although melatonin did not prevent the initial appearance of white matter lesions, it did promote secondary lesion repair. Axonal markers supported the hypothesis that melatonin induced axonal regrowth or sprouting. The protective effects of melatonin were suppressed by coadministration of luzindole, a melatonin receptor antagonist. Forskolin, an adenylate cyclase activator, prevented the protective effects of melatonin; inhibitors of protein kinase C and mitogen-associated protein kinase had no detectable effect. Melatonin and derivatives that block cAMP production through activation of melatonin receptors could represent new avenues for treating human periventricular leukomalacia. PMID- 11782989 TI - Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. AB - We investigated the basis for a novel form of the slow-channel congenital myasthenic syndrome presenting in infancy in a single individual as progressive weakness and impaired neuromuscular transmission without overt degeneration of the motor endplate. Prolonged low-amplitude synaptic currents in biopsied anconeus muscle at 9 years of age suggested a kinetic disorder of the muscle acetylcholine receptor. Ultrastructural studies at 16 months, at 9 years, and at 15 years of age showed none of the typical degenerative changes of the endplate associated with the slow-channel congenital myasthenic syndrome, and acetylcholine receptor numbers were not significantly reduced. We identified a novel C-to-T substitution in exon 8 of the delta-subunit that results in a serine to phenylalanine mutation in the region encoding the second transmembrane domain that lines the ion channel. Using Xenopus oocyte in vitro expression studies we confirmed that the deltaS268F mutation, as with other slow-channel congenital myasthenic syndrome mutations, causes delayed closure of acetylcholine receptor ion channels. In addition, unlike other mutations in slow-channel congenital myasthenic syndrome, this mutation also causes delayed opening of the channel, a finding that readily explains the marked congenital weakness in the absence of endplate degeneration. Finally, we used serial morphometric analysis of electron micrographs to explore the basis for the progressive weakness and decline of amplitude of endplate currents over a period of 14 years. We demonstrated a progressive widening and accumulation of debris in the synaptic cleft, resulting in loss of efficacy of released neurotransmitter and reduced safety factor. These studies demonstrate the role of previously unrecognized mechanisms of impairment of synaptic transmission caused by a novel mutation and show the importance of serial in vitro studies to elucidate novel disease mechanisms. PMID- 11782990 TI - Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. AB - Apolipoprotein E has been implicated in modifying neurological outcome after traumatic brain injury, although the mechanisms by which this occurs remain poorly defined. To investigate the role of endogenous apolipoprotein E following acute brain injury, noninvasive magnetic resonance imaging was performed on anesthetized mice following closed head injury. Effacement of the lateral ventricle was used as a radiographic surrogate for cerebral edema. At 24 hours following injury, apolipoprotein E-deficient animals had a greater degree of cerebral edema as compared to matched controls. In addition, the brains of apolipoprotein E-deficient animals had a significantly greater upregulation of tissue necrosis factor alpha messenger ribonucleic acid as compared to controls as early as 1-hr post injury. Thus, modulation of the endogenous central nervous system inflammatory response may be one mechanism by which apolipoprotein E affects outcome following acute brain injury. PMID- 11782991 TI - Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. AB - The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA(Ile) gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject. PMID- 11782992 TI - Increase in hand muscle strength of stroke patients after somatosensory stimulation. AB - It has been proposed that somatosensory input in the form of peripheral nerve stimulation can influence functional measures of motor performance. We studied the effects of median nerve stimulation on pinch muscle strength (a function mediated predominantly by median nerve innervated muscles) in the affected hand of chronic stroke patients. A 2-hour period of median nerve stimulation elicited an increase in pinch strength that outlasted the stimulation period. The improvement in muscle strength correlated with stimulus intensity and was identified in the absence of motor training. These results suggest that somatosensory stimulation may be a promising adjuvant to rehabilitation of the motor deficits in stroke patients. PMID- 11782993 TI - Selective hippocampal neuron loss in dementia with Lewy bodies. AB - Hippocampal volume and neuron number were measured using stereological techniques in pathologically confirmed dementia with Lewy bodies (n = 8), Parkinson's disease only (n = 4), and controls (n = 9). We, and others, have previously shown considerable cell loss in the CA1 and subiculum subregions in Alzheimer's disease. In contrast, these regions were spared in dementia with Lewy bodies where a selective loss of lower presubiculum pyramidal neurons was found. These findings suggest a selective loss of frontally projecting hippocampal neurons in dementia with Lewy bodies versus those projecting to temporal lobe regions in Alzheimer's disease. PMID- 11782994 TI - A novel, blood-based diagnostic assay for limb girdle muscular dystrophy 2B and Miyoshi myopathy. AB - Limb girdle muscular dystrophy 2B and Miyoshi myopathy were recently found to be allelic disorders arising from defects in the dysferlin gene. We have developed a new diagnostic assay for limb girdle muscular dystrophy 2B and Miyoshi myopathy, which screens for dysferlin expression in blood using a commercially available monoclonal antibody. Unlike current methods that require muscle biopsy for immunodiagnosis, the new method is simple and entails a significantly less invasive procedure for tissue sampling. Moreover, it overcomes some of the problems associated with the handling and storage of muscle specimens. In our analysis of 12 patients with limb girdle muscular dystrophy 2B or Miyoshi myopathy, the findings obtained using the new assay are fully consistent with the results from muscle immunodiagnosis. PMID- 11782995 TI - Association studies of multiple candidate genes for Parkinson's disease using single nucleotide polymorphisms. AB - We studied 20 single nucleotide polymorphisms in 18 candidate genes for association with Parkinson's disease. We found that homozygosity for the V66M polymorphism of the brain-derived neurotrophic factor (BDNF) gene occurs more frequently in patients with Parkinson's disease than in unaffected controls (chi(2) = 5.46) and confirmed an association with the S18Y polymorphism of the UCH-L1 gene. Our results provide genetic evidence supporting a role for BDNF in the pathogenesis of Parkinson's disease. PMID- 11782996 TI - Monozygous twins discordant for epilepsy. PMID- 11782997 TI - Discontinuing chronic aspirin therapy: another risk factor for stroke? PMID- 11782998 TI - MRI in Leigh syndrome with SURF1 gene mutation. PMID- 11783000 TI - Parallel concept of migraine pathogenesis. PMID- 11783003 TI - Progress in sequencing the mouse genome. PMID- 11783004 TI - Cell and tissue requirements for the gene eed during mouse gastrulation and organogenesis. AB - Mouse embryos homozygous for the allele eed(l7Rn5-3354SB) of the Polycomb Group gene embryonic ectoderm development (eed) display a gastrulation defect in which epiblast cells move through the streak and form extraembryonic mesoderm derivatives at the expense of development of the embryo proper. Here we demonstrate that homozygous mutant ES cells have the capacity to differentiate embryonic cell types both in vitro as embryoid bodies and in vivo as chimeric embryos. In chimeric embryos, eed mutant cells can respond to wild-type signals and participate in normal gastrulation movements. These results indicate a non cell-autonomous function for eed. Evidence of mutant cell exclusion from the forebrain and segregation within somites, however, suggests that eed has cell autonomous roles in aspects of organogenesis. A requirement for eed in the epiblast during embryonic development is supported by the fact that high contribution chimeras could not be rescued by a wild-type extraembryonic environment. PMID- 11783005 TI - Prolonged survival of mouse epididymal spermatozoa stored at room temperature. AB - The viability and fertility of isolated mouse epididymal spermatozoa kept for up to 7 days at various temperatures (4 degrees C, 22 degrees C, and 37 degrees C) were determined. Spermatozoa kept for 3 days at 22 degrees C were still active, while those kept at 37 degrees C or 4 degrees C exhibited great reduction in motility within 2 days after isolation. In vitro fertilizing abilities of spermatozoa left for 0, 1, 2, and 3 days at 22 degrees C were 69.2, 32.5, 9.5, and 4.9%, respectively, when the cleavage rate to two-cell stage was examined. Transfer of two-cell embryos produced in vitro with spermatozoa left for 1, 2, and 3 days at 22 degrees C resulted in production of fetuses with efficiencies of respectively 30.2, 11.5, and 16.7%, which were lower (63.3%) than that of embryos derived from in vitro fertilization with fresh spermatozoa. These findings indicate that spermatozoa kept for up to 3 days at 22 degrees C can fertilize oocytes, although at relatively low efficiency. PMID- 11783006 TI - Multiple enhancers contribute to expression of the NK-2 homeobox gene ceh-22 in C. elegans pharyngeal muscle. AB - Gene expression in the pharyngeal muscles of C. elegans is regulated in part by the NK-2 family homeodomain factor CEH-22, which is structurally and functionally related to Drosophila Tinman and the vertebrate Nkx2-5 factors. ceh-22 is expressed exclusively in the pharyngeal muscles and is the earliest gene known to be expressed in this tissue. Here we characterize the ceh-22 promoter region in transgenic C. elegans. A 1.9-kb fragment upstream of ceh-22 is sufficient to regulate reporter gene expression in a pattern identical to the endogenous gene. Within this promoter we identified two transcriptional enhancers and characterized their cell type and temporal specificity. The distal enhancer becomes active in the pharynx near the time that ceh-22 expression initiates; however, it becomes active more broadly later in development. The proximal enhancer becomes active after the onset of ceh-22 expression, but it is active specifically in the ceh-22-expressing pharyngeal muscles. We suggest these enhancers respond to distinct signals that initiate and maintain ceh-22 gene expression. Proximal enhancer activity requires a short segment containing a CEH 22 responsive element, suggesting that CEH-22 autoregulates its own expression. PMID- 11783007 TI - Toucan protein is essential for the assembly of syncytial mitotic spindles in Drosophila melanogaster. AB - The toc gene of Drosophila melanogaster encodes a 235-kD polypeptide with a coiled-coil domain, which is highly expressed during oogenesis (Grammont et al., 1997, 2000). We now report the localization of the Toucan protein during early embryonic development. The Toucan protein is present only during the syncytial stages and is associated with the nuclear envelope and the cytoskeletal structures of the syncytial embryo. In anaphase A, Toucan is concentrated at the spindle poles near the minus end of microtubules. This microtubule association is very dynamic during the nuclear cell cycle. Mutant embryos lacking the Toucan protein are blocked in a metaphase-like state. They display abnormal and nonfunctional spindles, characterized by broad poles, detachment of the centrosomes, and failure of migration of the chromosomes. These results strongly suggest that Toucan represents a factor essential for the assembly and the function of the syncytial mitotic spindles. PMID- 11783009 TI - [Chromosome locus of ATRA-induced gene RA109 and intracellular localization of RA109 protein]. AB - OBJECTIVE: To define chromosome locus of ATRA-induced gene RA109 and intracellular localization of its encoding protein. METHODS: Chromosome locus was defined by radiation hybrid mapping method and protein localization by green fluorescence protein (GFP) as reporter molecule. RESULTS: RA109 gene was mapped to chromosome 5q35 and its protein was localized in cell nucleus. CONCLUSION: RA109 gene is mapped by radiation hybrid technique to a chromosome region that is rich in disease-related genes. The RA 109-encoding protein is a nucleoprotein. PMID- 11783008 TI - Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. AB - Nkx2-5, one of the earliest cardiac-specific markers in vertebrate embryos, was used as a genetic locus to knock in the Cre recombinase gene by homologous recombination. Offspring resulting from heterozygous Nkx2-5/Cre mice mated to ROSA26 (R26R) reporter mice provided a model system for following Nkx2-5 gene activity by beta-galactosidase (beta-gal) activity. beta-gal activity was initially observed in the early cardiac crescent, cardiomyocytes of the looping heart tube, and in the epithelium of the first pharyngeal arch. In later stage embryos (10.5-13.5 days postcoitum, dpc), beta-gal activity was observed in the stomach and spleen, the dorsum of the tongue, and in the condensing primordium of the tooth. The Nkx2-5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes. PMID- 11783010 TI - [Expression and function of protein kinase C-alpha and beta I isoenzymes in drug resistant gastric cancer cells]. AB - OBJECTIVE: To study the expression and function of PKC-alpha and beta I isoenzymes in drug-resistant cells of gastric cancer. METHODS: Two tumor cell lines were used in the study: gastric cancer SGC7901 and its drug-resistant counterpart SGC7901/VCR stepwise-selected by various concentrations of vincristine. The expression of PKC-alpha and beta I isoenzymes in SGC7901 and SGC7901/VCR was detected by immunohistochemistry, laser confocal scanning microscopy and Western blot. The effects of anti-PKC-alpha or beta I antibody on adriamycin accumulation in SGC7901/VCR cells were determined by flow cytometric analysis. RESULTS: SGC7901 cells exhibited positive staining of PKC-alpha. The staining of PKC-alpha in SGC7901/VCR was stronger than that in SGC7901 cells. The higher the concentrations of vincristine, the stronger staining of PKC-alpha was observed on SGC7901/VCR cells. Both SGC7901 and SGC7901/VCR cells were positive for PKC-beta I, but without difference in staining intensity. Comparing with SGC7901, SGC7901/VCR cells showed decreased adriamycin accumulation; the decrease was more marked with the increase in concentrations of vincristine for selection of cells. Increased adriamycin accumulation in SGC7901/VCR was observed when co incubated with anti-PKC-alpha but not anti-PKC-beta I antibodies. CONCLUSION: PKC alpha may play a role in multidrug resistance of gastric cancer cells SGC7901/VCR. PMID- 11783011 TI - [Cloning of drug resistance-related gene fragments differentially expressed on lung adenocarcinoma cell line A549 and its DDP-resistant counterpart A549DDP]. AB - OBJECTIVE: To clone drug resistance-related genes of lung adenocarcinoma. METHOD: The difference in gene expression between A549 and A549DDP was identified by mRNA differential display technique. Genes differentially expressed were cloned and confirmed by Northern blot. RESULTS: Four cDNA fragments of differentially expressed genes were obtained and sequenced. Of the 4 cDNA fragments, 2 (A1 and D1) did not show sequence homology with the existing genes in the GeneBank, one (A2) was 89% homologous with interleukin 1 beta converting enzyme (ICE) gene, and the other (D2) was identical to mouse musculus 45s pre-rRNA (MM45srRNA) gene. Both cDNA fragments A1 and A2 were expressed in A549 but not or barely expressed in A549DDP, while fragments D1 and D2 were expressed in A549DDP but not in A549. CONCLUSION: Four differentially expressed gene fragments between lung adenocarcinoma cell line and its cisplatin-resistant counterpart were identified by mRNA differential display technique. It remains to be studied whether the newly identified gene fragments and those showing sequence homology to ICE and MM45srRNA are indeed positively or negatively related to drug resistance. PMID- 11783012 TI - [Investigation on the relationship between MDR and expression of N glycosphingolipids in vincristine resistant KBv200 cell line]. AB - OBJECTIVE: To study the relationship between MDR and expression of N glycosphingolipids (H-GSLs) in tumor cells. METHODS: Ribozyme with specific catalytic activity, capable of cleaving mdr1 mRNA, was transfected into KBv200 cells. RNA dot blot was used to detect the expression of ribozyme in the transfected cells. Northern blot and immunocytochemistry were employed to examine the expression of mdr1 mRNA and P-glycoprotein. Cellular N-GSLs was isolated and purified with a modified Hakamori's method and analysed by high performance TLC. The effect of DL-PPMP, a glycolipids synthase inhibitor, on the reversion of MDR was assayed by MTT method. RESULTS: The ribozyme stably expressed in KBv200/5mR3 cells decreased the level of mdr1 mRNA expression by 81.9% and inhibited the formation of P-glycoprotein. The levels of monohexosylceramide (CMH) and dihexosylceramide (CDH) in KBv200 cells were increased as compared to those in KB cells. When MDR was reversed by the ribozyme, the KBv200/5mR3 showed a sharply decreased level of CMH. PPMP could reverse MDR by inhibiting synthesis of CMH. CONCLUSION: CMH is a kind of MDR-related glycolipid. Inhibition of its expression in tumor cells may be a new approach to reverse MDR. PMID- 11783013 TI - [Experimental study of anti-metastasis effect of urokinase amino-terminal fragment gene on human breast cancer cells]. AB - OBJECTIVE: To explore the suppressive effects of urokinase amino-terminal fragment (ATF) gene on metastatic potential of human breast cancer cell line MCF 7. METHODS: A pcDNA3-ATF plasmid containing ATF cDNA under CMV promotor/enhancer control was constructed and transfected into MCF-7 cells by lipofectin. The expression of of uPA/uPAR and ATF in MCF-7 cells were analyzed by RT-PCR and Western blot. The effect of ATF expression on invasiveness in vitro, tumorigenesis and metastasis in vivo of MCF-7 cell was investigated. RESULTS: MCF 7 cells displayed an overexpression of uPA/uPAR. Expression of ATF was detected after ATF gene-transfection. The invasive capacity of ATF gene-transfected MCF-7 cells was decreased significantly. Although the tumorigenesis was not affected, the in vivo metastasis of ATF gene-transfected MCF-7 cells was remarkably inhibited. CONCLUSION: Suppression of invasiveness and metastasis of ATF transfected MCF-7 cells is perhaps due to a competitive inhibition of interaction with endogenous uPA/uPAR. PMID- 11783014 TI - [Anti-tumor immune response against mouse melanoma to xenogeneic vaccination]. AB - OBJECTIVE: To study the inhibition of melanoma growth in mice by vaccination with xenogeneic melanocytes. METHODS: Xenogeneic vaccine was prepared from pig eye melanocytes. It was used before or after B16 melanoma challenge in C57 mice. The size of tumor was monitored. Cytotoxic T lymphocyte (CTL) activity of mouse spleen cells was measured by 51Cr release assay. Antibody response against pig melanocytes and B16 melanoma cells were detected by indirect ELISA. RESULTS: Preventive vaccination resulted in inhibition of tumor growth in 90% of the immunized mice, while therapeutic vaccination inhibited tumor growth in 50% of the treated mice. Specific CTL activity and antibodies in the immunized mice were detected. CONCLUSION: Anti-tumor immune response capable of inhibiting melanoma growth can be induced by xenogeneic melanocyte vaccination. PMID- 11783015 TI - [Expression of extraneuronal monoamine transporter gene and DNA repair gene vis-a vis with antitumor efficacy of SarCNU in human tumor xenografts]. AB - OBJECTIVE: To clarify if there are any correlations between extraneuronal monoamine transmitters (EMT), DNA repair gene expressions and SarCNU antitumor efficacy. METHODS: EMT, DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) and excision repair cross-complementing rodent repair deficiency gene (ERCC1-6) expressions in 9 human xenograft tumor models were determined by RT PCR. The results were compared with the antitumor effects of SarCNU on these tumor xenografts. RESULTS: Multiple regression analysis revealed significant correlations of SarCNU antitumor activity with different combinations of gene expression. The most significant correlation was observed with all of the 4 genes expressed. CONCLUSION: The results suggest that expression of both EMT and DNA repair genes, specifically, MGMT, ERCC2 and ERCC4, are important determinants of SarCNU activity against human tumors. While DNA repair decreases SarCNU's activity by repairing damaged DNA, EMT appears to enhance its antitumor efficacy. PMID- 11783016 TI - [Influence of focal adhesion kinase (FAK) on the biological behaviors of human hepatocellular carcinoma cells]. AB - OBJECTIVE: To study the effect of reducing FAK expression on the malignant biological behaviors of FAK-overexpressed hepatocellular carcinoma cell line SMMC 7721. METHODS: FAK expression of different hepatocelluar carcinoma cell lines was detected by Western blot analysis. Antisense plasmid of FAK was constructed and transfected into SMMC-7721. RESULTS: SMMC-7721 expressed much more FAK than did hepatocyte line L02. When transfected with autisense FAK, it showed reduced growth rate and colony formation in soft agar, and the number of cells in S phase was reduced by 15%. The adhesion ability of antisense FAK-transfeected cells was also decreased with no change of integrin expression. CONCLUSION: FAK is overexpressed in the human hepatocellular carcinoma cell line SMMC-7721. Reducing the FAK expression can partly reverse the malignant behaviors of the cell line. PMID- 11783017 TI - [Abnormal expression of p53, Ki67 and iNOS in human esophageal carcinoma in situ and pre-malignant lesions]. AB - OBJECTIVE: To investigate alterations in expression of Ki67, p53 and iNOS proteins in esophageal carcinogenesis. METHODS: The expression of Ki67, p53 and iNOS proteins was detected by immunohistochemical staining of 366 endoscopic biopsy specimens of the esophagus collected from high incidence area of esophageal cancer in China. If the intensity of staining was scored as > or = ++, it was regarded as overexpression. RESULTS: The overespression rate of Ki67 was 0 for normal epithelium(NE), 2.7% for mild dysplasia (MD), 11.2% for moderate dysplasia (MoD), 41.2% for severe dysplasia (SD), and 58.8% for carcinoma in situ(CIS), respectively. That of p53 and iNOS proteins was 0 and 0 for NE, 10.1% and 4.0% for MD, 24.5% and 7.5% for MoD, 39.2% and 2.5% for SD, 48.7% and 1.4% for CIS, respectively. There was significant difference in the expression of Ki67 and p53 between normal epithelium and dysplasia of various degrees and CIS. Overexpression of Ki67 and p53 correlated well with the pathological grading of the lesions. Positive correlation was also found between p53 and Ki67 overexpressions. CONCLUSION: Overexpression of Ki67 and p53, but not iNOS, is associated with carcinogenesis of the esophagus. They are early events in esophageal carcinogenesis and useful biomarkers for early detection. PMID- 11783018 TI - [Study of loss of heterozygosity at chromosome 11q13 in nasopharyngeal carcinoma]. AB - OBJECTIVE: To analyze the loss of heterozygosity (LOH) from STS sites at 11q13 in nasopharyngeal carcinoma(NPC). METHODS: Relatively pure tumor tissues were obtained by microdissetion. PCR was used to perform microsatellite analysis of NPC samples using D11S4946, PYGM, D11S449 and INT-2 as primers, which span the MEN-1 gene. RESULTS: Thirty-six of 38 cases studied showed LOH in at least one of the loci analyzed. Among the primers used, D11S4946 had the highest frequency of LOH, (78.8%). The LOH frequency was 51.5% for INT-2, 45.5% for PYGM and 45.7% for D11S449, respectively. CONCLUSION: The high frequency of loss of heterozygosity at 11q13 in NPC implies that there may be some tumor suppressor gene(s) involved in NPC tumorigenesis. PMID- 11783019 TI - [Deletion mapping of chromosome 18q and Smad proteins expression analysis in urinary bladder carcinomas]. AB - OBJECTIVE: To investigate the role of loss of heterozygosity (LOH) on chromosome 18q in the carcinogenesis and progression of urinary bladder cancer and to provide clues for early detection and positional cloning of related genes. METHODS: Deletion mapping was performed on 18q using 12 microsatellite markers. Immunohistochemistry staining was used to evaluate the expression level of two tumor suppressor candidates Smad 2 and Smad 4 in this region. RESULTS: LOH in at least one of the 12 microsatellites on 18q was detected in 84.2% (32/38) of patients with bladder cancer. The minimal deletion region included tumor suppressor candidate Smad 4. Immunohistochemical study revealed that 21.1% (8/38) of the cases had up-regulated Smad 2 protein and 34.2% (13/38) of the cases had down-regulated Smad 2 protein. Smad4 protein expression was down-regulated in 68.4% (26/38) of the cases but up-regulated Smad 4 expression was seen in only one case. CONCLUSIONS: LOH on 18q was closely linked with bladder cancer. The irregular expression of tumor suppressor candidates Smad 2 and Smad 4 may play important role in the initiation and progression of bladder neoplasms. PMID- 11783020 TI - [Expression level of c-erbB-2 protein correlates with the prognosis of patients with colorectal cancer]. AB - OBJECTIVE: To study the expression level of c-erbB-2 gene in colorectal cancer and its correlation to prognosis. METHODS: In 173 colorectal carcinoma patients, c-erbB-2 protein was examined immunohistochemically and patients' prognosis was evaluated by retrospective analysis combined with follow-up data. RESULTS: The immunohistochemical staining of c-erbB-2 protein was found in the cytoplasm and membrane with a positive rate of 52% in tumor tissue. The 1-, 3-, 5- and 10-year survival rate of patients with negative c-erbB-2 expression was 98.7%, 92.4%, 87.1% and 84.1% respectively; that of the patients with weakly positive c-erbB-2 expression was 94.5%, 76.1%, 72.3% and 68.3%, respectively. In contrast, that of patients with strongly positive c-erbB-2 expression was 91.0%, 43.5%, 36.8% and 23.4%, respectively. The survival rates among the three groups of patients were statistically different. Multivariate survival analysis by Cox regression model showed that c-erbB-2 expression level was a risky prognostic factor for colorectal cancer. CONCLUSION: The expression level of c-erbB-2 protein is an independent prognostic factor in colorectal carcinoma. PMID- 11783021 TI - [Study of the route of intrahepatic metastasis of primary hepatic carcinoma]. AB - OBJECTIVE: To study the relationship between pylic countercurrent blood-flow and intrahepatic metastasis of hepatocarcinoma. METHODS: Portal vein-hepatic artery fistula and pylic countercurrent blood flow in the liver were examined by color Doppler ultrasound. Patients examined were divided into four groups: group 1, hepatocarcinoma with background of hepatitis, group 2, hepatocarcinoma without background of hepatitis, group 3, hepatitis and group 4, normal liver. RESULTS: Pylic countercurrent flood flow was most frequently observed in group 1 patients. Intrahepatic metastasis was more frequent in group 1 than in group 2 patients. There was no statistically significant difference in the frequency of portal vein hepatic artery fistula formation around and inside of tumor between group 1 and group 2 patients. CONCLUSION: Intrahepatic metastasis of hepatocarcinoma is due to countercurrent blood flow in the portal system. PMID- 11783022 TI - [CT virtual bronchoscopy in the diagnosis of central lung cancer]. AB - OBJECTIVE: To evaluate the clinical application of CT virtual bronchoscopy(VB) in the diagnosis of centrally located lung cancer. METHODS: Forty-five cases confirmed by fiberoptic bronchoscopy and pathology underwent volume scanning using spiral CT (HiSpeed Advantage CT/i. GE Medical Systems, U.S.A). The patients examined included 33 with central lung cancer, 8 with post-operative residual bronchial stumps, 2 with post-radiotherapy lung cancer, and 2 with tracheal carcinoma. Data were transferred to computer workstation (GE Advantage Windows 3.1) and CT virtual bronchoscopic (CTVB) images with pseudocolor encoding were generated using Navigator Smooth soft-ware. RESULTS: CTVB could reveal 100% segmental bronchus and 80% subsegmental bronchus simulating fiberoptic bronchoscopy. The tumors appeared as masses or nodules, causing bronchial wall thickening and occlusions. Post-operative residual bronchial stumps showed smooth end without recurrence of tumors or appeared as nodular protrusion if tumor recurred. The post-radiotherapy bronchial wall was uneven and there was narrowing of bronchial lumen. CONCLUSION: CTVB is a noninvasive method of observing the airway. It stimulates the images observed under fiberoptic bronchoscopy and com be used partly in lieu of it. Associated with multiplanar reformat, CTVB can demonstrate extraluminal invasion of the tumor. The limitations of CTVB are that it is not possible to observe mucosal abnormalities and perform biopsy. PMID- 11783023 TI - [Microscopic measurement of the surgical resection margins of laryngeal carcinomas]. AB - OBJECTIVE: To investigate the relationship between the primary sites of laryngeal carcinomas and the surgical resection margins, to obtain quantitative data of the safe distance of surgical margins for supraglottic and glottic carcinomas. METHODS: In this series, 33 cases of surgical specimens of laryngeal carcinomas were examined and measured microscopically by means of cutting strips of tissues adjacent to the tumor and longitudinal serial sections. RESULTS: The pattern and extent of invasion of supraglottic carcinoma were quite different from those of glottic carcinoma. Under microscopic measurement, the tumor invasion distance in 95% of the supraglottic carcinoma samples was within 10.52 mm, while that of 95% of the glottic carcinoma samples was within 4.41 mm. CONCLUSIONS: The local invasion of laryngeal carcinomas appears to be primary tumor site-dependent. The safe distance of surgical resection margins may be set at 12.52 mm and 6.41 mm for supraglottic and glottic carcinomas, respectively. PMID- 11783024 TI - [Clinical study of topotecan in the treatment of small cell lung cancer and recurrent ovarian cancer]. AB - OBJECTIVE: To evaluate the effect and adverse reaction of China made topotecan in the treatment of small-cell lung cancer (ACLC) and recurrent ovarian cancer (OV). METHODS: From January to July, 2000, topotecan was used to treat 141 patients at a dose of 1.2 mg/m2, given daily as 30-min i.v. infusion for 5 days. Treatment was repeated once every 3 weeks. Of the 141 patients, 118 were evaluable for therapeutic efficacy. All the patients received a total of 286 cycles of treatment were assessable for analysis of adverse reactions. RESULTS: Among the evaluable patients, there were 5 CR, 35 PR, with an overall response rate (RR) of 33.8%. There were 3 CR and 26 PR in 89 patients with SCLC (RR 32.5%). The response rate of patients with or without prior chemotherapy was 15.6% and 50%, respectively. In 29 patients with recurrent OV, there were 2 CR and 9 PR (RR 37.9%). The major toxic effect was myelosuppression. Non-hematopoietic toxicities were mild and tolerable. CONCLUSION: Topotecan is an effective drug for the treatment of SCLC and recurrent OV. It is still efficacious in some patients who previously received standard chemotherapy. The major dose-limiting toxicity is myelosuppression. The response rate and toxicity of the domestically made topotecan are comparable with those of the imported one. PMID- 11783025 TI - [Mobilization of autologous peripheral blood stem cells by combined chemotherapy and rhG-CSF]. AB - OBJECTIVE: To study the effect of cyclophosphamide (CTX) combination chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on autologous peripheral blood stem cells (APBSC) mobilization. METHODS: CTX(2.5 +/- 1.0) g/m2 on day 1, VP-16,600-800 mg and/or Ara-C 1.0-2.0 g/m2 on day 2 were injected i.v. rhG-CSF 300 micrograms/d was injected s.c. when the white blood cell (WBC) count reached nadir until one day before APBSC harvest. When the WBC count was over 3.0 x 10(9)/L, peripheral blood mononuclear cell (MNC) collection was performed once per day until the number of MNC collected was > 4 x 10(8)/kg. CFU-GM colony formation and CD34+ cell enumeration were performed. RESULTS: Twenty cases were studied. The lowest level of WBC was (1.2 +/- 0.8) x 10(9)/L on day 8.5 +/- 1.5 following chemotherapy. rhG-CSF was given from day 9.0 +/- 2.0 and continued for 6.0 +/- 1.0 days. APBSC harvest began on day 12.0 +/- 2.0 and continued for 4.0 +/- 1.0 days. A total of (6.14 +/- 2.34) x 10(8)/kg MNC and (23.25 +/- 30.56) x 10(6)/kg CD34+ cells was procured. Peak level of CD34+ cells was observed 14.6 +/- 1.8 days after chemotherapy and 4.9 +/- 1.6 days after rhG CSF administration. CFU-GM was (21.68 +/- 15.39) x 10(4)/kg when rhG-CSF was given for 4.9 +/- 1.6 days. No severe toxic reaction was observed. Hematopoietic reconstitution was very well in all patients received APBSC transplantation. CONCLUSION: CTX combination chemotherapy followed by rhG-CSF was safe and feasible for APBSC mobilization. PMID- 11783026 TI - [Carcinoma of kidney collecting duct: an analysis of 10 cases]. AB - OBJECTIVE: To study the clinicopathologic characteristics of renal collecting duct carcinoma (CDC). METHODS: A retrospective study was done in 10 cases of CDC. RESULTS: Among 466 cases of renal cell carcinoma admitted in our Institute between January 1989 and June 30, 1999, 10(2.1%) cases of CDC were identified. Seven presented with gross hematuria and 3 with abdominal pain. Radical nephrectomy was done in 9 patients, enucleation of tumor in one. The primary tumor was located predominantly in the renal medulla. Histologic examination showed prominent tubular or tubulopapillary structures. Sarcomatoid carcinoma, cystadenocarcinoma, nests and cords of tumor cells in desmoplastic stroma were identified in some cases. High molecular weight cytokeratin 34 beta E12 was positive in 8 cases and peanut agglutinin in 7 cases. According to Fuhrman's nuclear grade, one was in G2, 4 were in G3 and 5 in G4. Six patients died of metastases within 3 to 23 months (mean 13.3 months), one died of heart disease with tumor free after 19 months, two survived with tumor free for 14 months and 39 months, respectively, one lost from follow-up. CONCLUSION: CDC is a distinctive renal cell carcinoma with prominent clinical appearance and progressive clinical course. PMID- 11783027 TI - [Transarterial chemoembolization with high dose iodized oil for the treatment of large hepatocellular carcinoma]. AB - OBJECTIVE: To report the method and result of high dose iodized oil chemoembolization for the treatment of large hepatocellular carcinoma. METHODS: From 1993 to 1998, 163 patients with unresectable hepatocellular carcinoma were treated by transarterial chemoembolization (TACE) with more than 20 ml lipiodol. RESULTS: TACE with high dose lipiodol was well tolerated by the treated patients. In patients whose liver function was of Child A stage, or in patients whose residual indocyanine green level 15 min after injection was less than 20%, the frequency of post-treatment hepatic insufficiency was not significantly different from that of patients treated with routine dose of lipiodol. On CT scan at 4 wk after TACE, more lipiodol was located in the liver. The 1-, 2-,3-year survival rate of patients in Child A stage was 79.8%, 50.3%, and 38.5%, respectively, as compared to 57.5%, 24.8% and 8.37%, respectively in patients treated with routine dose of lipiodol (P = 0.0136). CONCLUSION: High dose lipiodol TACE for the treatment of large hepatocellular carcinoma is practically acceptable with better therapeutic effect but its use should be limited to those patients with compensated liver function. PMID- 11783028 TI - [Therapeutic effect on glioblastoma of chemotherapy on the basis of brain irradiation]. AB - OBJECTIVE: To study the efficacy of chemotherapy for glioblastoma on the basis of brain irradiation. METHODS: It was previously reported that the permeability of the blood brain barrier (BBB) to methotrexate could be increased by brain irradiation. In this study, glioblastoma patients were divided into 2 groups, 28 patients in each group. On group of patients was treated with CCNU or BCNU after having given 20-40 Gy irradiation to the brain. The other group of patients received radiation treatment alone. RESULTS: The 1-, 3-, and 5-year survival rate of the two groups of patients was 57.1%, 22.5%, 15.0% and 17.9%, 7.1%, 3.6%, respectively. The median survival time was 29.7 +/- 7.0 and 9.7 +/- 3.5 months, respectively (P < 0.001). CONCLUSION: Increase in permeability of the BBB after 20-40 Gy brain irradiation may provide an optimal chance for intracranial chemotherapy of glioblastoma. PMID- 11783029 TI - [A comparative clinical study of carboplatin solution and carboplatin powder]. AB - OBJECTIVE: To observe the efficacy and side effects of carboplatin solution in comparison with carboplatin powder. METHODS: A multicenter, open randomized controlled trial was carried out. A total of 121 patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and breast cancer (BC) were randomized into carboplatin injection group (study group) and carboplatin powder group (control group), treated with CE, CIE and CAF protocol, respectively. The same drugs and dosage were used in the two groups. RESULTS: The response rate of the study group and the control group was 94% and 67% in SCLC (P > 0.05), 12% and 22% in NSCLC (P > 0.05) and 71.4% and 67% in BC (P > 0.05), respectively. The major side effects were myelosuppression and gastrointestinal reactions, the frequency and intensity of which were statistically not different in the 2 groups of patients. CONCLUSION: Carboplatin solution is as effective as carboplatin powder for the treatment of cancer. PMID- 11783030 TI - [The relationship between cyanotoxin (microcystin, MC) in pond-ditch water and primary liver cancer in China]. AB - OBJECTIVE: To explore the relationship between primary liver cancer (PLC) and MC in drinking pond-ditch water. METHODS: Epidemiological and ecological assays, Meta-analysis and risk assessment were used in this study. Cyanotoxin (Microcystin, MC) in the water of different sources was detected by ELISA. The F344 and HBVx transgenic mice were used to confirm the promotion effect on PLC and the synthetically carcinogenic effect of HBV, aflatoxin and MC. RESULTS: Using Meta-analysis the results of six case-control studies showed that the pooled odds ratio (OR) was 2.46 (95% CI 1.69-2.59), population attributable rick (PAR) was 30.39% (95% CI, 23.30%-37.47%), heterogeneity test P > 0.05. Eutrophication led to cyanobacterial bloom in the pond-ditch water. Cyanotoxin released from dead cyanobacteria was hepatotactic tumor promoter. In HBVx transgenic rats, hepatocellular carcinoma was induced by the joint administration of aflatoxin B1 and cyanotoxin. Epidemiological study showed that the recombined index of HBsAg, aflatoxin-albumin adducts and drinking of pond-ditch water correlated with PLC mortalities in 13 townships. CONCLUSION: Microcystin in the pond-ditch water is a hepatotactic toxin which can induce hepatitis and promote development of hepatocellular carcinoma. The combined effect of microcystin, HBV and aflatoxin may be responsible for the endemicity of PLC. PMID- 11783031 TI - [Sanitary characteristics of bottled drinking water]. AB - In this communication we intend to highlight the main characteristics of the natural mineral waters, the spring waters, the prepared potable waters and the public consumption waters conjuncturally bottled, all of then admitted by the Spanish legislation as "bottled drinking waters", among which we do not find mineral medicinal waters, due to their widely known therapeutical effectiveness, which places them in an independent group. It is made reference to the "table waters", nice to the taste and favorable for the health but without concrete therapeutical effects. Among these waters we can to detach the carbogaseoses waters. Finally, the importance of the bottled drinking waters is fundamental in the extreme ages of life: in the baby born children and also in their first months of life as well as in the elderly. PMID- 11783032 TI - [Cellular polarization]. AB - The principal ideas of Dr. Santiago Ramon y Cajal are commented. 1. Theory of the dynamic polarization. 2. Transmission of electric signals in the neuronal synapsis. 3. The static description is guided by a dynamic concern. 4. In cancer patients without hope, the positive effect of our metabolic treatment is impressive. 5. Two cases are presented that could avoid cardiac transplantation with our treatment. 6. The nice poem of Alfonso Camin, entitled "We went to bury him to a mountain" is presented. PMID- 11783033 TI - [The wild children: myth or reality?]. AB - Although Car von Linne described in 1758 on his Systema Naturae the feral man because their characters hirsutus, tetrapus and mutus, he done this work upon 9 children lifted in the forest and suckled by animals. Malson, in 1964, described 53 wild children. The author of these paper, after an analysis of the history and general facts of the actually known wild children, arrives to the deduction that survival and characters of the wild children find the explanation in the recent memetric theory. PMID- 11783034 TI - [Is it possible to measure illness intensity degree?]. AB - First Dr. Abad gave thanks to his teachers, to Excelentisimo Mr. President and to the Illustrious Academics of the Royal National Academy of Medicine, to other people and to the auditory. This investigation belongs to Objective Medicine being applicable to Medicine, Pharmacy and Veterinary, that is to say, to the Sciences of the Health. After examining the clinical history he made an analysis of the selected research premises. Among others he analysed what are denominated bigger and smaller symptoms, what means the penetration and the symptomatic invasion, what is a hidden illness, the metastatic condition, what is typical and atypical of a clinical diagram, the problem of previous illnesses with repercussion on the current one (comorbility), the influence of the syntomatology, the immunity and the psyche about the quality of life; lastly the histopatologic factors. These concepts belong to the nosology and the propedeutics (semiotecnics and semiology). The material of the investigation consists on a database, for the time being of more that 6.600 terms, corresponding to the pathology, which is enlargeable and amendable. Each term has been classified by seven concepts. It has been proceeded to an unification of the language, avoiding the polisemia, by means of another database of more than 5.000 key-words that later on have transformed in determinants. The Method, starting from the determinants, built a Biological Scientific Model of 30 groups, applicable to the Medicine which produces a Virtual Real Image of the sintomatology. The results obtained are those that next are described. Grouping the data of the 30 groups he finally obtained a Virtual Real Image of the illness, of eight bases, denominated Nosoma which indicates the variations, from the psychic to the organic field, during the evolution and pursuit of the illness. You can make a quality of life analysis on the different stages of the illness that, together with the value of the symptoms, by means of an algorithm, produces an Nosometric Index, which indicates a valuation of improvement or sick person worsening. This index serves as a control of the therapeutic effectiveness on studies or clinical rehearsals. The system also obtains the valuation of sequels and inabilities upon an illness or accident, and either it's adequate to value patient's death caused by illness in course or for the comorbility, confronting it with the autopsy. By means of this Index, together with the data describing patient's evolution obtained by the computer's program, it's possible to establish doctor's defence parameters against juridical problems. PMID- 11783035 TI - [Drug treatment of Alzheimer's disease]. AB - The Alzheimer's disease is caused by a today unknown plurietiopathology that does not allow to establish an effective treatment. In the last years, important advances about neuronal physiology and its molecular bases of functioning has been attempt. At the same time, the research and finding of medicaments which used individually or together allow us to advance from a symptomatic treatment to influence and be effective etiopathologically in the Alzheimer's disease. A few are trying to maintain the structure and function of the neurons (synapsis). Others are concentrated on prevent their death or substitute the damaged cells by embryonic mother cells. Nowadays, there are important projects in an experimental stage of research with the hope that "they will be useful for everything" or unless to slow down or stop the Alzheimer's disease. We are going to talk about these medicaments in this article. PMID- 11783036 TI - [Medical errors or deviations in daily health care practice]. AB - There is since 1991 an increasing preoccupation in the English medical literature on adverse events and it has caused that the Institute of Medicine (IOM) has written in 1998 a report that has driven the American Government to make some national plans to find a solution to the problem and to create a committee which deal with the Quality of Health Care in America with the participation of outstanding figures of the policy, sanitary administration, and medical scientific societies. There are deviations between 3.7 and 45.8 in hospital stay. They have Mortality between 4.9 and 5.6. From those between, a 51% and a 54% can be avoided. Only a 27% can be considered as negligence. Deviations happen only a few times because of an isolated personal human factor, but they are associated with many different ocassional and underlying reasons. The analysis of those reasons is essential to understand and to help preventing repetition of that facts. Adverse events does not in many cases mean a training failure but an error in the way that a physician act at a certain moment. The cognitive psychology tries to explain the way that memory behaves, reasoning, and human performance. Adverse events could be not so often, if all the efforts could be driven in direction of prevention, and not in direction of legal punishment. The industry have a lot of experience in applying norms, which could be adapted to any sanitary system, as it is shown in civil aviation industry. All the sanitary personnel should collaborate and this is fundamental to know the facts and the circumstances. However it requires confidentiality and absence of retaliation. It is a fact that there are deviations and its importance requires a cultural change to transform a traditionally defensive attitude into a collaborating conduct in order to improve the quality of the attendance. PMID- 11783037 TI - [Giving up life in the labyrinth]. AB - A brief historic survey of the labyrinth, from prehistoric images carved in stone, to gardens, Renaissance drawings and architectonic constructions will presented. The metaphor of the labyrinths, which began with Theseus killing the Minotaur with the help of Ariadne, can be applied to all: scientific investigation, artistic creation, wickedness, theology ... to life. In these eculiar and chaotic designs, structural simplicity and functional complexity coincide and therefore may produce repeated erroneous decisions. To wander successfully through these labyrinths, caution and repeated decision-makings are required to enable the traveller to reach the desired and elusive center. In each instant, decisions are made in our mind as a consequence of complex cerebral systems, activated by stimuli which originate in the intimate regions of the mind, the most complex labyrinth of all. These types of mental labyrinths are immaterial, without paths or walks, where each successive decision made facing multiple bifurcations, causes the mental traveller to advance until reaching the center. This center deceptively becomes the entrance to another of the innumerable and unknown mental labyrinths that the intimate life proposes. PMID- 11783038 TI - [The remarkable symptoms of the temporal lobe dysfunction]. AB - From all the cerebral regions, except the orbito-frontal area of the frontal lobe, especially on the right hemisphere, the temporal lobe is the best connected region of the cerebral cortex with the limbic system. The disorders of the temporal lobe produce symptoms which affect many behaviors, like sexuality, visual perceptions, recognizing familiar faces, perception of emotional expressions, and even religious beliefs. They can also affect personal relationships, the perception of the "ego", with depersonalization and derealization phenomena; in short, behaviors which are essential to the human being. PMID- 11783039 TI - [What are the prions?]. PMID- 11783041 TI - [Pathological anatomy of spongiform encephalopathies]. PMID- 11783040 TI - [Spongiform encephalopathies in humans]. PMID- 11783042 TI - [Bovine spongiform encephalopathy]. AB - An historical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID- 11783043 TI - [Spongiform encephalitis]. AB - The authors present a personal interpretation of the pathogeny of prionic processes, showing the role played by heredity. They also present the very surprising fact that a protein codified by a mutant gene can act as transmissible agent in a serious illness opening new chapters to the pathology of a series of important diseases. This is a completely new perspective in the biology. PMID- 11783044 TI - [Socio-sanitary considerations on bovine spongiform encephalopathies and new variant of Creutzfeldt-Jakob disease]. PMID- 11783045 TI - Calcium signals and synaptic short-term plasticity in the central nervous system. AB - Plastic changes in the connectivity between neurons underly the adaptive information processing of the central nervous system. The shortest forms of such plasticity are synaptic depression and facilitation, which happen on the subsecond time scale. New techniques allow to study synaptic transmission at unprecedented resolution and to dissect its various components, such as presynaptic Ca++ currents, Ca++ signals, and transmitter stores. Precise knowledge on the components, which are altered during plastic changes, is essential for understanding these important mechanisms. PMID- 11783046 TI - [Bile duct injury is a disaster for both the patient and the surgeon. Routine intraoperative radiography in cholecystectomy is recommended]. PMID- 11783047 TI - [No documented therapeutic effect of immunoglobulin in severe sepsis and septic shock. Cochrane review is a shot that hit the post!]. PMID- 11783048 TI - [Comment to a Cochrane review. HFOV or conventional ventilation for newborn infants with severe respiratory failure]. AB - The Cochrane review of the use of high frequency oscillatory ventilation in newborns more than 34 weeks gestation only included one randomized study and therefore gives an incomplete picture of the use of HFOV as rescue therapy for this patient group. The study was stopped prematurely due to difficulties in patient recruitment. There is a real need for more randomized studies but increasing use of HFOV has made these studies very difficult to perform. From the existing data routine use of HFOV in this patient group cannot be recommended. Experience of using HFOV in one Swedish tertiary care center during the years 1993-1998 is described. Eighty seven newborns were treated with HFOV rescue with 69 percent patient survival while 91 percent of the surviving infants were extubated directly to nasal continuous positive airway pressure. Intraventricular hemorrhage was seen in 9 patients. PMID- 11783049 TI - [An observational study requires careful consideration by the reader]. AB - The observational study has its merits when randomized controlled studies are impossible to perform. This review discusses its merits and weaknesses for a reader of such studies. The reader has to consider the internal and external validity of the study and its role in the establishment of causal relationships and estimations of risks. The reader is recommended to primarily evaluate the quality of study design, confounding and measurement bias, rather than to try to understand if an advanced statistical analysis is correct. The possibilities of misleading results are discussed. PMID- 11783050 TI - [High number of bile duct injuries in cholecystectomy. There is a connection with the use of the laparoscopic technique]. AB - During the 1990s 152 cases with injuries of the bile ducts in connection with cholecystectomy in 81% performed via laparoscopic technique were reported to the Swedish Patients' Insurance Company. In 116 cases there was a lesion of the common duct, in 24 cases there was a defect in the duct. A peroperative cholangiogram was carried out in more than two thirds of the cases. Lesions of the common duct could in most cases be repaired with suture and drainage. In 44 cases, however, a Roux anastomosis to the small intestine had to be performed. To prevent bile duct injuries during cholecystectomy, the anatomy of the operative field must be clarified before tubular structures are divided. Peroperative cholangiography as routine during cholecystectomy is recommended. PMID- 11783051 TI - [Ruptured abdominal aortic aneurysm. Endovascular treatment under local anesthesia]. AB - We report on endovascular repair of a ruptured abdominal aortic aneurysm. A bifurcated stent graft was inserted under local anesthesia. Aortic clamping is rapidly provided by percutaneous placement of an aortic occlusion balloon catheter. Carbon dioxide can usually replace conventional contrast in patients with renal insufficiency. This minimally invasive procedure may reduce perioperative morbidity and mortality in patients with ruptured aortic aneurysms. The advantages and limitations of this novel technique are discussed. PMID- 11783052 TI - [Therapeutic program for ascites. Recommendations from the Swedish Society of Gastroenterology and Gastrointestinal Endoscopy]. AB - As ascites is related to liver cirrhosis in 80% of the patients, the present therapeutic guidelines are focused on ascites in liver cirrhosis. A combination of spironolactone and furosemide is recommended as first line therapy in patients with mild to moderate ascites and is effective in 90% of patients. In patients with pronounced or tense ascites, first line treatment is total paracentesis with intravenous infusion of human albumin as colloid replacement. Maintenance therapy for the prevention of recurrent ascites is based on spironolactone with or without furosemide. The indications for peritoneovenous shunt, or transjugular intrahepatic stent-shunt (TIPSS), are limited and only recommended in strictly selected patients with refractory ascites. Ascites in liver cirrhosis is a symptom of advanced liver disease, and liver transplantation should always be considered in eligible patients. PMID- 11783053 TI - [Both risky and "healthy" factors in the allergy prevention counseling]. AB - Most recommendations in order to prevent childhood allergy are based on data gained in retrospective studies. In future it is important that such recommendations are based on intervention studies. Results from prospective birth cohort studies may also be used, since ethical issues must be taken into consideration when interfering on matters like parental smoking, breast-feeding, the keeping of furred pets and the unsuitability of living in damp houses. PMID- 11783054 TI - [Difficulties in the treatment of psychosis in young patients with epilepsy]. AB - Diagnostic considerations and treatment strategies in adolescents with partial complex epilepsy and emerging psychosis are discussed. We will argue for considering clozapine early in treatment if other antipsychotics have failed based on two cases; these patients both developed epilepsy in early childhood and schizophrenia in mid adolescence. Their partial complex epilepsy were unsuccessfully treated with different antiepileptic drugs. Clozapine was tried with a distinct improvement in psychotic symptoms and functional level. In both cases there was an early unexpected improvement in seizure control on clozapine. It appears that a reduction of psychotic activity improved seizure control. Later on, there appeared to be a trade off between clozapines effect on psychotic symptoms and recurrence of seizure activity. CONCLUSION: A schizophrenic development must be taken into consideration if psychiatric symptoms emerge in adolescents with a partial complex epileptic disorder. Clozapine treatment can be considered if other antipsychotic drugs are ineffective or cause motor side effects. PMID- 11783055 TI - [Autism-spectrum disorder is not rare, can be traced early and requires early intervention!]. PMID- 11783056 TI - [Prone position doesn't improve survival of patients with acute respiratory failure]. PMID- 11783057 TI - [Crimean-Kongo hemorrhagic fever in Kosovo]. PMID- 11783058 TI - [To grow without growing taller. How far will the striving of perfectionism go?]. PMID- 11783059 TI - [Microsatellite instability in renal cell carcinoma and its mechanisms]. AB - OBJECTIVE: To study the expression of microsatellite instability (MSI) in renal cell carcinoma (RCC) and its relationship with gene mutation. METHODS: Tumor samples from 34 patients with RCC were analyzed for MSI by PCR. RT-PCR was used to evaluate the expression of mRNA of 5 human mismatch repair (MMR) genes in RCC and RCC cell lines. Mutation of hMLH1 gene coding regions was detected by PCR SSCP. PCR was used to check the mutations of TGF-beta R II gene and BAX gene in 15 MSI-positive samples of RCC. RESULTS: Microsatellite changes were detected in 15 of 34 patients with RCC (44.1%). It might be associated with the progression of this disease. There were 3 of 15 MSI-positive RCC cases without expression of MMR gene hMLH1, and in 3 of 15 cases its expression was decreased. All 5 MMR genes were expressed in normal and RCC 949 cell line. There were three mutations in 15 MSI-positive cases. Frame shift mutation of TGF beta R II gene and BAX gene was found in 6 and 4 of the 15 cases with MSI, respectively, but it was not found in MSI-negative RCC and normal tissue. CONCLUSION: MSI and expression of MMR genes are associated events in RCC. The effect of gene mutation on tumorgenerasis may be related to MSI. PMID- 11783060 TI - [A study on cyclooxygenase-2 protein expression in esophageal carcinoma and premalignant lesions]. AB - OBJECTIVE: To investigate cyclooxygenase-2(Cox-2) protein expression in esophageal cancer and precancerous lesions. METHODS: One hundred twenty biopsy specimens from patients with esophageal carcinoma, 113 from patients with esophageal premalignant lesions, 27 from individuals with normal esophageal mucosa and 3 from Barrett's esophagus were examined for Cox-2 protein expression by immunohistochemistry. RESULTS: Cox-2 protein was not observed in normal esophageal squamous and glandular epithelium, hyperplasia from mild to severe dysplasia lesions and carcinoma in situ. Positive Cox-2 expression was found in 4 of 60 specimens of invasive squamous-cell carcinomas, 21 of 30 specimens of esophageal adenocarcinomas and in 3 of 3 Barrett's esophageal tissues. CONCLUSION: The Cox-2 protein expression may be associated with the development of the esophageal adenocarcinomas but not esophageal squamous-cell carcinomas. PMID- 11783061 TI - [Preliminary study on skeletal muscle derived tumor suppressor]. AB - OBJECTIVE: To investigate the effect of new born rat skeletal muscle conditioned medium (MCM) on proliferation of tumor cells, and its physicochemical characteristics and mechanisms of action. METHODS: The effects of MCM were tested on a variety of cells by MTT assay. MCM was also tested following ultrafiltration, boiling at 100 degrees C and treatment with trypsin. Morphology and apoptosis of the MCM-treated cells were examined. RESULTS: Proliferation of mouse myeloma SP2/0, rat carcino-sarcoma Walker 256, and tumor cell lines of human origin, including leukemia K562 and HL-60, colon adenocarcinoma LS-174-T, prostatic carcinoma PC3-M, and lung adenocarcinoma with low(PLA801-C) and high(PLA801-D) metastatic potential were significantly decreased when cultured with MCM(P < 0.01-0.05) in a dose-dependent manner. The proliferation of normal cells(RGP-2 rabbit joint epiphysial disk cells) was not affected by MCM. Proliferation of the lung adenocarcinoma with high metastatic potential was more susceptible to the growth inhibitory effect of MCM as compared to that with low metastatic potential. On ultrafiltration, the inhibitory activity of MCM existed in the fraction with a molecular weight < or = 10,000. It was trypsin resistant but thermolabile. Apoptosis was not seen but the cytoplasmic membrane of tumor cells was destroyed after cultured in MCM. CONCLUSION: Rat skeletal muscle cells produce low molecular weight tumor suppressor(s) capable of selectively inhibiting tumor cell proliferation in vitro. Its activity is neither species- nor tumor-specific. The skeletal muscle derived tumor suppressor(s) may play a key role in the rarity of tumor metastases in skeletal muscles. PMID- 11783062 TI - [The effect of rhIL-11 on hematopoiesis of rhesus monkeys irradiated with 60Co gamma-rays]. AB - OBJECTIVE: To study the therapeutic effect of recombinant human interleukin-11 (rhIL-11) on acute radiation sickness in monkeys. METHODS: rhIL-11 (30, 60, 120 micrograms.kg-1.d-1, s.c., on days 0-13 after TBI) or vehicle was administered to rhesus monkeys irradiated with 3.0 Gy 60Co gamma-rays. RESULTS: The nadirs of platelet count were significantly improved after treatment with rhIL-11. The duration of platelet and leukocyte numbers below 50% of their baseline values was shortened. Erythrocyte recovery was also accelerated. Semi-solid bone marrow cell culture demonstrated that rhIL-11 could stimulate monkey's bone marrow cell to form more CFU-MK, CFU-Mix, CFU-E and BFU-E in vitro, especially at the dose of 60 micrograms.kg-1.d-1. Histopathological observation revealed that bone marrow of the untreated controls showed large area of bleeding whereas that of the rhIL-11 treated monkeys was in active proliferation. CONCLUSION: rhIL-11 can accelerate hematopoietic recovery of monkeys received 3.0 Gy total body gamma-rays irradiation. PMID- 11783063 TI - [Telomerase activity of common malignant tumors]. AB - OBJECTIVE: To study the usefulness of detection of telomerase activity in the diagnosis of malignant tumors. METHODS: Modified telomeric repeat amplification protocol (TRAP) was employed to examine telomerase activity in 283 malignant tumor tissues, 42 adjacent tissues and 61 benign tumor tissues. RESULTS: Of the 283 malignant tumors and 42 adjacent tissues, telomerase was positive in 264 (93.3%) and 11 (26.1%), respectively. Only 4 of the 62 (6.6%) benign tumors were telomerase positive. CONCLUSION: Telomerase activity may be used as tumor marker in the diagnosis of malignant tumors. PMID- 11783064 TI - [Preliminary assessment of articles reporting cancer diagnostic tests]. AB - OBJECTIVE: To improve the quality of papers on clinical diagnostic tests. METHODS: Articles of diagnostic tests published in the Chinese Journal of Oncology in the year 1990 were surveyed by cluster sampling method. RESULTS: In the 23 articles surveyed, immunoassays constituted the largest category, accounting for 39.1% (9/23), followed by biochemical markers and radiological tests, accounting for 17.4% (4/23) and 13.0%(3/23), respectively. Of the 23 articles, 19 (82.6%) employed a well-defined "gold standard", 14 (60.9%) correctly calculated sensitivity and specificity. The interpretation of the test was stated to be "blind" in only 39.1%(9/32). In only one paper were all the seven methodologic criteria adhered. Less than 60% of the articles followed more than four of the seven methodologic criteria, and in 2 articles only one of the criteria was met with. CONCLUSION: Although due attention has been paid to the methodologic criteria of assessing diagnostic tests, the quality of the articles surveyed needs to be improved. PMID- 11783065 TI - [mRNA expression and mutation of MTA1 and nm23H1 genes in ovarian carcinoma in relation to lymph node metastasis]. AB - OBJECTIVE: To investigate mRNA expression and mutation of MTA1 and nm23H1 genes in ovarian carcinoma (OC) in relation to lymph node (LN) metastasis. METHODS: A panel of eight normal ovarian tissues, twenty primary OC specimens and twenty corresponding LNs was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by using RT-PCR and RT-PCR-SSCP. The level of expression was determined by the relative optic density (ROD) of the PCR products. RESULTS: The frequency of MTA1 overexpression was 100% (7/7) in primary OC with metastasis but only 38.5% (5/13) in those without metastasis (P = 0.0103). Overexpression of MTA1 was observed in 87.5% (6/7) of LNs with metastasis but in only 23% (3/13) of LNs without metastasis (P = 0.0118). In contrast with MTA1, low expression of nm23H1 mRNA was seen in 7 of 7 OC with metastasis but only in 4 of 13 (30%) of those without metastasis (P = 0.0043). Low nm23H1 expression was also seen in 7 of 7 LNs with metastasis but only in 5 of 13 (38.5%) nonmetastatic LNs (P = 0.0102). The ROD ratio of MTA1 to nm23H1 increased with the development of metastasis. No mutation of MTA1 and nm23H1 was found by SSCP analysis. CONCLUSION: The mRNA expression of MTA1 and nm23H1 is positively and negatively correlated with LN metastasis, respectively. Expression abnormalities but not mutation of the two genes are frequent events related to LN metastasis of ovarian cancer. PMID- 11783066 TI - [The clinical significance of E-cadherin and alpha-catenin expression in human gastric cancer]. AB - OBJECTIVE: To evaluate the expression of cell adhesion molecules E-cadherin (E CD) and alpha-catenin (alpha-CA) in relation to biologic behavior of gastric cancer. METHODS: The level of E-CD and alpha-CA expression was examined in 70 cases of primary gastric cancer by immunohistochemical technique. RESULTS: The rate of E-CD and alpha-CA expression was significantly reduced in gastric cancer with more prominent malignant phenotype, such as tumor in stage III/IV with poor cell differentiation, invasion through serosa and lymph node (LN) metastasis. With the increase in the number and frequency of LN metastasis and its dissemination distal to second group LNs, the reduction in expression of the two adhesion molecules was increasingly significant. The frequency of LN metastasis and shed cancer cells in the peritoneum in patients with E-CD(-)/alpha-CA(-) and E-CD(+)/alpha CA(-) cancer were significantly higher than those in patients with E-CD(+)/alpha-CA(+) tumor. Liver metastasis was most frequent in all cases with E CD(+)/alpha-CA(-) tumor. CONCLUSION: Down regulation of E-CD and/or alpha-CA correlates with the malignant behavior of gastric cancer. Examination of E-CD and alpha-CA expression in primary gastric cancer helps evaluate its intensity of LN metastasis, TNM staging and prognosis. PMID- 11783067 TI - [Expression of glutathione S-transferase-pi in human esophageal squamous cell carcinoma]. AB - OBJECTIVE: To evaluate the expression of glutathione S-transferase-pi (GST-pi) in human esophageal squamous cell carcinoma (ESCC) and its correlation with the clinicopathological data. METHODS: Immunohistochemical method (labeled avidin biotin method) and ELISA were used to detect the expression of glutathione S transferase-pi (GST-pi) in 143 cases of formalin fixed, paraffin embedded ESCC tissue sections. Serum GST-pi was determined before and after operation in 43 patients with ESCC. RESULTS: GST-pi was positively stained immunohistochemically in 58.7%(84/143) of ESCC and 79.6%(109/139) of surrounding noncancerous esophageal tissues (P < 0.05). The expression level of GST-pi was significantly higher in well differentiated than poorly differentiated carcinomas(P < 0.05). No significant correlation was observed between GST-pi levels and lymph node metastasis, pathological staging or long term survival. The preoperative and postoperative mean serum GST-pi levels in ESCC patients were significantly higher than those in 34 normal subjects (P < 0.05, P < 0.025); the mean serum GST-pi level in postoperative patients was lower than that in preoperative patients, but the difference was not significant. CONCLUSION: GST-pi is a useful tumor marker for human ESCC. PMID- 11783068 TI - [Extent of lymphadenectomy in stage I-IIIA non-small cell lung cancer: a randomized clinical trial]. AB - OBJECTIVE: To study the role of radical systematic mediastinal lymphadenectomy for non-small cell lung cancer (NSCLC). METHODS: All 504 operable eligible cases with NSCLC were randomly divided to a radical lymphadenectomy (RL) group and a conventional lymph node dissection group (control) treated between Aug. 1989 and Dec. 1995. For patients postoperatively eligible, thirteen parameters (operation type, pathological type and grade, tumor size, total number of dissected lymph nodes, number of metastatic lymph nodes, metastasis ratio of lymph nodes, postoperative TNM staging, adjuvant therapy, recurrence or metastasis, morbidity, survival and life quality) were evaluated. The end point of follow-up was Dec. 31, 1998. Lost follow-up rate was 1.9%. The results were analyzed with soft were SPSS7.5. The cumulative survival was calculated by the Kaplan-Meier method and compared by the log rank test. The prognostic factors were analyzed by the Cox model. RESULTS: There were 320 cases, 160 cases in each group, who entered the study. The mean numbers of dissected lymph nodes was 9.49 in the RL group and 3.63 in the control group. For stage I NSCLC patients, the 1,3,5,9-year survival rate was 91.8%, 86.9%, 81.4%, 74.2% respectively in the RL group and 88.7%, 72.5%, 58.5%, 52.1% respectively in the control group (P < 0.014). However, no statistically significant difference in survival rates between RL and control groups of patients with stage II and IIIA NSCLC. The postoperative TNM staging, metastasis ratio of lymph nodes, extent of lymphadenectomy were the factors influencing long term survival upon multivariable analysis. CONCLUSION: Classical lobectomy or pneumonectomy with radical systematic mediastinal lymphadenectomy is the surgical treatment of choice for NSCLC. PMID- 11783069 TI - [Clinical significance of CD44 expression in ovarian epithelial tumors]. AB - OBJECTIVE: To study the clinical significance of the adhesion molecule CD44 expression in ovarian epithelial tumors and its relation to the clinical manifestation of ovarian cancer. METHODS: The expression of CD44 protein and mRNA was examined by immunohistochemistry, RT-PCR, nested PCR and densitometric scanning. The correlation between CD44 expression and clinicopathological features was analyzed. RESULTS: In comparison with benign ovarian tumors, CD44H protein expression was significantly higher in ovarian cancer in terms of positive rate as well as the level of expression. The levels of mRNA expression in ovarian cancer positively correlated with the grade and stage. The CD44H mRNA expression level in primary tumor correlated with that in the metastatic lesions. High levels of expression of CD44H mRNA predicted poor survival probability. The expression rate of CD44V3, CD44V4/5 and CD44V6 protein was 21.2%, 19.2% and 15.4% respectively in ovarian cancer as compared to 3.1%, 12.5% and 0 in benign tumors. There was significant difference between the two groups in CD44V6. CONCLUSION: Epithelial carcinoma of ovary expresses high level of CD44H. The amount of CD44H mRNA expression increased with progression of ovarian cancer. It can serve as a predictor of prognosis. It may play an important role in the peritoneal dissemination of ovarian cancer. Expression of CD44V6 is characteristic of malignant ovarian epithelial tumor. PMID- 11783070 TI - [Distal intramural spread of rectal cancer studied on large slices]. AB - OBJECTIVE: To study the length of distal intramural spread of rectal cancers, and provide evidence for anal-preserving operations. METHODS: Specimens of ninety eight patients with rectal cancers who had been operated from August, 1996 to October, 1997, were collected and their large pathologic slices examined. The length of intramural spread distal to rectal cancers was measured under light microscope. The actual length of spread in live conditions was estimated according to equal proportional shrinkage. RESULTS: In 48 of the 98 patients, distal intramural spread of the tumor was observed. The length of spread varied from 0.1 cm to 2.5 cm. In 77% of the 48 patients, the length of tumor spread was < 0.5 cm. In only 5 patients was the distance of spread > or = 1.0 cm. Four different ways of tumor invasion were observed: contiguous, lymphatic, neural and venous invasion. Distal intramural spread could be via mucosa, submucosa, inner circular muscular layer, outer longitudinal muscular layer or serosa, either separately or concomitantly. CONCLUSION: Distal intramural spread of rectal cancers can be detected in about 1/2 of the specimens examined on large pathologic slice. In most of them the distance of spread is < 0.5 cm. Occasionally it may be > or = 1 cm. To set the edge of resection > or = 3 cm distal to the rectal cancers is relatively safe in anal-preserving operations. PMID- 11783071 TI - [Immunoelectron microscopic analysis of P-glycoprotein, p53, and Bcl-2 proteins expressions in lung cancer]. AB - OBJECTIVE: To determine the ultrastructural localization of P-gp, p53 protein, and Bcl-2 protein in lung cancer cells, their relation to multidrug resistance and possible mechanisms of action. METHODS: Expression of P-gp, p53, and Bcl-2 proteins was examined in 8 NSCLC surgical specimens and 7 SCLC bronchoscopically biopsied specimens using postembedding PAG immunolabelling technique for electron microscopy. RESULTS: P-gp was detected on the cell membrane and the periphery of endoplasmic reticulum (ER). P53 protein was observed not only in the nuclei associated with heterochromatin but also in the cytosol. Bcl-2 protein immunoreactivity was associated with mitochondria and ER. P-gp, p53, and Bcl-2 were detected in 5(33%), 9(60%), and 4 (26.7%) out of the 15 samples examined, respectively. In 8 normal lung tissues, these three proteins were detected. Of 5 P-gp positive samples 4 were NSCLC, only 1 was SCLC after chemotherapy. CONCLUSION: P-gp, p53, and Bcl-2 proteins are detectable immuno-electron microscopically in lung cancer cells. No correlation in expression existed between of p53 and P-gp, nor did that between p53 and Bcl-2. The plasma membrane localization of P-gp supports its action as a transmembrane drug efflux pump. P gp may play a role in MDR in lung cancer. PMID- 11783072 TI - [An analysis of clinicopathologic features affecting prognosis of thymoma]. AB - OBJECTIVE: To discuss the relationship between the clinicopathologic characteristics and prognosis of thymoma. METHODS: One hundred and thirty cases of thymoma were analyzed in terms of myasthenia gravis(MG), tumor size, necrosis, mitosis, capsule, histologic type according to the Lattes-Bernatz(L-B) classification and Muller-Hermelink(M-H) classification, staging according to Masaoka. RESULTS: Association with MG, size of tumor, necrosis, mitosis and L-B classification were of no prognostic significance. The survival rate was higher in patients with a well encapsulated tumor. According to the M-H subtypes, the prognosis was better in patients in medullary type than in patients with cortical type thymoma. In patients with well-differentiated thymic carcinoma(WDTC), their 5-year survival rate was 43.4%, and none survived at 10 years. The survival of patients decreased with the increase in clinical stage of the disease. Cell atypia and invasion of neighboring organs were of prognostic impact on survival. CONCLUSION: Histologic typing according to M-H classification and clinical staging according to Masaoka, cell atypia and invasion to neighboring organs are of prognostic value in patients with thymoma. PMID- 11783073 TI - [Detection and diagnosis of small peripheral lung cancers less than 15 mm in diameter]. AB - OBJECTIVE: To assess the value of chest film, conventional CT (CCT), Spiral CT (SCT) and high resolution CT (HRCT) for detection and diagnosis of small peripheral lung cancers less than 15 mm in diameter. METHODS: Chest film, CCT, SCT and HRCT were taken in 59 cases of peripheral lung cancers less than 15 mm in diameter confirmed by operation and pathology. Their value in the diagnosis was analysed retrospectively. RESULTS: In 47% of chest films and 17% of CCT, the small lung cancer was not detected. However no tumor escaped detection by SCT. HRCT was superior for showing density and detailed image signs compared to chest film and CCT. The CT features of small peripheral lung cancers was different from those of larger peripheral lung cancers. CONCLUSION: The SCT is the best method for detection, and HRCT for diagnosis of small peripheral lung cancers less than 15 mm in diameter. PMID- 11783074 TI - [Evaluation of methods of detection for prostate neoplasm]. AB - OBJECTIVE: To evaluate the significance of serum prostate specific antigen (PSA), digital rectal examination (DRE), transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) as guide to perform prostate needle biopsy. METHODS: One hundred forty-eight patients suspicious of prostate neoplasm were undergone transrectal ultrasound-guided prostate needle biopsy. The pathologic diagnosis was analyzed in association with the results of PSA, DRE, TRUS and MRI in various combinations. RESULTS: The positive rate of biopsy was 43.9%. While abnormal DRE or PSA contributed in the detection of prostate cancer, serum PSA became more reliable when combined with DRE, TRUS or MRI, but the contribution of each of the three diagnostic procedures was not significantly different. The sensitivity of MRI was higher than that of DRE or TRUS, whereas TRUS was more specific than PSA or MRI. CONCLUSION: RE and PSA can be used for preliminary screening of prostate cancer. When combined with TRUS and MRI, the positive rate of diagnosis is increased. So is the specificity of the diagnosis which helps avoid unnecessary needle biopsy. PMID- 11783075 TI - [Evaluation of intraperitoneal chemotherapy in stage IV gastrointestinal cancer]. AB - OBJECTIVE: To evaluate the short term and long term therapeutic effects of intraperitoneal versus intravenous chemotherapy in 56 cases with stage IV gastrointestinal cancer. METHODS: The patients were randomly divided into two groups: 35 cases in the intraperitoneally treated group and 21 cases in the intravenously treated group. The short term effects and side effects were observed. The survival time of the patients was also recorded. The survival function was estimated by Kaplan-Meier method, and the significance test was done by Log rank method. RESULTS: There was no significant difference between the two groups in short term effects, and liver and kidney damages. Nausea, vomiting and bone marrow suppression were more severe in the intravenously treated group, while abdominal distension and pain were the major side effects in the intraperitoneally treated group. The median survival time and one year survival rate of patients in the intraperitoneally treated group were higher than those in the intravenously treated group. CONCLUSION: For patients with stage IV gastrointestinal cancer, intraperitoneal administration of chemotherapeutic agents is a better treatment of choice. PMID- 11783077 TI - [Diagnosis and treatment of primary trigeminal neurilemmoma]. AB - OBJECTIVE: A series of 51 patients with trigeminal neurillemmoma were analyzed with respect to the clinical manifestations, radiologic features, operative approaches and factors influencing tumor total resection. METHODS: Three different approaches were used to remove the tumors according to the site of tumor growth. Tumors in middle fossa were removed via extended middle fossa approach or extended transpterion approach. Dumbbel tumors on petrosal bone were resected by presigmoid approach. Retrosigmoid approach was used to excise tumors in posterior fossa. RESULTS: Tumors removed completely in 80.0% of patients, 75.0% of the patients had a normal cranial nerve function after operation. Tumors recurred in two patients 2 years after operation. CONCLUSION: The new operative approach increases the complete tumor resection rate. PMID- 11783076 TI - [Carcinoid of trachea and bronchus: a report of 20 cases]. AB - OBJECTIVE: To understand the biologic and clinical characteristics of carcinoid tumor of trachea and bronchus and to find out rational surgical indications and approaches. METHODS: The clinical materials of 20 surgically treated patients with carcinoid of trachea and bronchus were retrospectively analyzed. RESULTS: All but one patient received radical tumor resection. Operative complication occurred in 2 patients. Of the 20 patients, 13 suffered from typical carcinoids (TC) and 7 from atypical carcinoids (AC). Immunochemical staining revealed that both the typical and atypical carcinoids were of neuroendocrine origin. The 5-, 10- and 15-year survival rate of TC patients was 100.0%, 7/8 and 3/4 respectively. Of the 7 patients with AC, 6 had not yet been 5 years after operation but were still alive, and one patient died of remote metastasis 2 years after operation. CONCLUSION: Surgical resection of carcinoid is indicated not only for early cases, but also for patients in stage III a and III b. The age and pulmonary function of the patients are the chief factors determining the surgical approach. PMID- 11783078 TI - [Experience and evaluation of extended resection and lymph nodes dissection in stage T3-4N2M0 lung cancer]. AB - OBJECTIVE: To report our experience of surgical treatment for stage T3-4N2M0 lung cancer. METHODS: One hundred thirty one patients with lung cancer in stage T3 4N2M0 were surgically treated by extended tumor resection, lymph nodes dissection and resection of ipsilateral mediastinal pleura and fatty tissue. RESULTS: The 3 year survival rate of patients in stage T3N2M0 with squamous-cell carcinoma and adenocarcinoma was 34% and 18%, respectively. That for stage T4N2M0 patients was only 13% and 5%, respectively. The survival rate was not improved in patients who received combination treatment in addition to surgery. CONCLUSION: The indication of extended resection with lymph node dissection in the treatment of T3-4N2M0 lung cancer is limited. PMID- 11783079 TI - [Mechanisms of arsenic trioxide-induced apoptosis in myeloma cells]. AB - OBJECTIVE: To investigate the possible mechanisms of arsenic trioxide (As2O3) induced apoptosis in multiple myeloma (MM) cell line, and the interactions between As2O3 and all-trans retinoic acid (ATRA) or interferon(IFN)-alpha. METHODS: Multiple myeloma cell lines RPMI 8226 and U266 were treated with As2O3 in combination with dithiothreitol (DTT), buthionine sulfoximine (BSO), ATRA and IFN-alpha. Cell viability was counted by trypan-blue exclusion. Apoptosis was assessed by cell morphology and flow cytometry. Mitochondrial transmembrane potentials (delta psi m) were measured by cellular rhodamine 123 staining intensity on flow cytometry. RESULTS: Glutathione depleting agent BSO at 1.0 mmol/L enhanced, while disulfide bond-reducing agent DTT at 0.2 mmol/L partially antagonized As2O3-induced decline of delta psi m and apoptosis in MM cells. ATRA also induced RPMI 8226 cell apoptosis, but it could not synergize with As2O3. On the other hand, As2O3-induced apoptosis did not occur in U266 cells. In addition, IFN-alpha itself did not inhibit the growth and viability of MM cells, nor did it influence the effects of As2O3 on MM cells. CONCLUSION: As2O3-induced apoptosis of RPMI 8226 multiple myeloma cells involves sulphyhydryl groups. ATRA and IFN alpha do not synergize with As2O3 in the induction of apoptosis of MM cells. PMID- 11783080 TI - [Subcellular distribution of daunorubicin in the P-glycoprotein-mediated multidrug-resistant cell line K562/ADR]. AB - OBJECTIVE: To examine subcellular distribution of daunorubicin (DNR) in P glycoprotein-mediated multidrug-resistant cell line K562/ADR and its relation to multidrug resistance. METHODS: The subcellular distribution of DNR in K562/ADR was studied by confocal scanning laser microscopy (CSLM), fluorometry, RT-PCR. Rhodamine 123, NBD-ceramide and neutral red as fluorescent probes to stain the mitochondria, Golgi apparatus and lysosomes respectively were used to identify the subcellular compartments wherein DNR was sequestered. Effect of verapamil, chloroquine and brefeldin A on DNR distribution and accumulation was examined. RESULTS: Compared with the drug-sensitive cell K562/S in which DNR fluorescence diffusely appeared in the nucleus and cytoplasm, DNR in K562/ADR cells was distributed to the perinuclear region and peripheral cytoplasm, It was scenty in the nucleus and other cytoplasmic regions, as suggested by the distribution of Rhodamine123. Only verapamil, but not chloroquine and brefeldin A, could markedly restore diffuse cytoplasmic and nuclear fluorescence distribution in the resistant cell line. CONCLUSION: Altered subcellular distribution of DNR in drug resistant cell line may participate in the generation of multidrug resistance in which P-glycoprotein plays an important role. PMID- 11783081 TI - [Immunogenicity of phage-displayed tumor antigen-mimic peptide]. AB - OBJECTIVE: To determine the immunogenicity of phage-displayed tumor antigen-mimic peptide, and to lay experimental foundation for the development of gastric cancer vaccine. METHODS: Based on previous studies, two phage-displayed peptide libraries were screened and 12 and 30 positive phage clones obtained from two libraries respectively. All the positive phages were purified and used them to immunize Balb/c mice. The immune serum was screened by immunohistochemical with tissue sections of human gastric cancer expressing MG7 antigen. The result was further confirmed by fluorescence labeling and ELISA. RESULTS: Through immunohistochemical screening of immune sera with tissue sections of human gastric cancer, one phage displayed mimic peptide was able to elicit production of antibody specific for human gastric cancer. CONCLUSION: The result demonstrates that it is possible to develop tumor vaccine based on antigen epitope mimic peptide with immunogenicity. PMID- 11783082 TI - [Docitaxol-induction apoptosis of osteosarcoma]. AB - OBJECTIVE: To study the growth inhibition and apoptosis induction effect of docitaxol on osteosarcoma cells. METHODS: The effect of docitaxol on osteosarcomat cell line PL-1 was examined by cell count, morphologic observation, flow cytometry (FCM) and electronmicroscopy. RESULTS: Docitaxol inhibited the growth of PL-1 in a time and dose-dependent manner. The osteosarcoma cells were blocked at G1 phase of the cell cycle. The treated cells presented features typical of apoptosis. Cells recultured shortly after being treated with docitaxol were more apt to undergo apoptosis than cells treated with docitaxol continuously. CONCLUSION: The growth inhibiting effect of docitaxol is due to its ability to induce apoptosis. It shows great potential in the treatment of osteosarcoma. PMID- 11783083 TI - [Apoptosis-related genes cloned by improved subtractive hybridization]. AB - OBJECTIVE: To clone apoptosis-related genes induced by all-trans retinoic acid (ATRA) from human breast cancer cell line MCF-7, and to analyze the association between the cloned genes and apoptosis. METHODS: An apoptotic cell model of MCF-7 cells was constructed with ATRA induction. The apoptosis-related genes were cloned by improved PCR-based subtractive hybridization. RESULTS: Twelve differentially expressed clones were screened out. After exclusion of false positive clones by reverse dot blotting, 5 clones containing fragments of 0.5-1.5 kb were sequenced. The results of sequencing were compared with BLAST. A novel gene, named apmcf-1, coding for 47 amino acids was identified. This gene was accepted by GenBank, (Accession number: AF141882). The result of reverse dot blotting showed that it was related to apoptosis. The other 4 genes were already known. Three of them were related to apoptosis as previously reported. Two of them, hsp-90 and rb-L3, had little information about their relationship with apoptosis. CONCLUSION: ATRA-induced tumor cell apoptosis is a complex process with multiple genes involved. PMID- 11783084 TI - [beta-elemene induces apoptosis of K562 leukemia cells]. AB - OBJECTIVE: To investigate the apoptosis-inducing effect of beta-elemene on K562 leukemia cells. METHODS: Hoechst 33342 and PI fluorescence staining, DNA fragmentation, electron microscopy, flow cytometry, and immunocytochemistry were used to evaluate the effect of beta-elemene on K562 cells. RESULTS: beta-elemene heatment induced the formation of apoptotic bodies and DNA ladder. The effect was dose- and time-dependent. The expression of bcl-2 was decreased in beta-elemene treated cells as compared with the untreated control cells. CONCLUSION: beta elemene exerts its cytotoxic effect on K562 leukemic cells by the induction of apoptosis. PMID- 11783085 TI - [EBV latent membrane protein 1 induces p53 expression via NF-kappa B in nasopharyngeal carcinoma]. AB - OBJECTIVE: To ascertain if EBV-encoded latent membrane protein 1 (LMP1) induces p53 expression via NF-kappa B signaling. METHODS: A nasopharyngeal carcinoma cell line, Tet-on-LMP1 HNE2, transfected with LMP1, the expression of which was regulated by tetracycline, was used in this study. Functional activity of NF kappa B was determined by luciferase reporter assay and expression of p53 and bcl 2 was detected by Western blot. RESULTS: LMP1 induced p53 expression via NF-kappa B signaling pathway. Induction of p53 expression could be blocked by phosphorothiate analogs of antisense oligonucleotides to NF-kappa B p65 and LMP1, but not by NF-kappa B p50. However, it seemed that LMP1 had no influence on bcl-2 expression in nasopharyngeal carcinoma. CONCLUSION: Induction expression of p53 by EBV-encoded LMP1 implies that p53 may act as a mediator in apoptosis triggered by LMP1, which brings about a complex balance in nasopharyngeal carcinogenesis. PMID- 11783086 TI - [Expression of two types of melanoma antigens in hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the expression of melanoma antigen MAGE-4 and MAGE-10 mRNA in Chinese human hepatocellular carcinoma (HCC). METHODS: The expression of MAGE-4 and MAGE-10 mRNA in HCC tissues and the adjacent non-HCC liver tissues was studied using RT-PCR in 48 samples of HCC. Ten samples of cirrhosis and 10 samples of normal liver tissues were examined. The PCR products were sequenced. RESULTS: Of the 48 HCC samples studied, 15 (31.3%) and 14 (29.2%) expressed MAGE 4 and MAGE-10 mRNA respectively. In contrast, none of the HCC adjacent non tumorous liver tissues were MAGE-4 and MAGE-10 mRNA detectable. Nor did liver tissues from cirrhosis and normal liver samples. The expression of the two genes in HCC showed no correlation with the serum level of AFP and the tumor size. CONCLUSION: MAGE-4 and MAGE-10 mRNA are specifically expressed in Chinese HCC samples. PMID- 11783087 TI - [Frequent chromosomal gain of 4q and loss of 1p in primary nasopharyngeal carcinoma]. AB - OBJECTIVE: To reveal the genetic changes of nasopharyngeal carcinoma (NPC) in Cantonese. METHODS: Comparative genomic hybridization (CGH) was performed on 17 primary NPC biopsy specimens to find out any gain or loss of genetic material. RESULTS: A novel copy number gain on chromosome 4q and loss of chromosome 1p were found at high frequency (> 50%). The other more common genetic alterations included gain of chromosomes 4q, 12q, and 1q as well as loss of chromosomes 1p, 3p, 11q, 14q, 15q, 13q, Xq, 9q, 10p, 10q, and 16q. CONCLUSION: Current analysis has revealed a comprehensive profile of the chromosomal changes in NPC. Frequently altered loci may encode oncogenes or tumor suppressor genes involved in the development of primary NPC. PMID- 11783088 TI - [Expression of VEGF, bFGF and ER in endometrial carcinoma]. AB - OBJECTIVE: To investigate the expression of VEGF, bFGF and ER in endometrial carcinoma and its relation to the clinico-pathological manifestations and prognosis. METHODS: A total of 66 specimens of endometrial carcinoma and 19 normal endometrium was studied by immunohistological technique with polyclonal antibodies against VEGF and bFGF, and monoclonal antibody against ER. RESULTS: Positive expression rate of VEGF in endometrial carcinoma was 80.3%. Expression of VEGF was positively correlated with tumor grade (P < 0.01). Expression of VEGF was positively correlated with that of bFGF (P < 0.05). Negative correlation was observed between ER expression and tumor grade (P < 0.05). Prognosis of patients with negative ER expression was poor. No correlation existed between ER expression and that of VEGF and bFGF. CONCLUSION: Expression of VEGF and bFGF may indicate that both of them contribute in the angiogenesis of endometrial carcinoma. Expression of ER has prognostic significance. PMID- 11783089 TI - [Bax gene expression in endometrial carcinoma]. AB - OBJECTIVE: To study the relationship between bax gene expression and endometrial carcinoma. METHODS: Bax mRNA expression was evaluated by RT-PCR in a series of 8 normal proliferative endometrium (NPE), 6 simple and complex hyperplasia (SCH), 6 atypical hyperplasia (AH) and 42 endometrial carcinoma (EC). RESULTS: All of the 8 NPE showed moderate bax mRNA expression. In 1 of 6 SCH, 2 of 6 AH and 27 of the 42 EC (64.3%), there was overexpression of bax mRNA. In endometrial carcinoma, with the progression of clinical stage, increase in histologic grade and in depth of invasion to muscle layer, and lymph node metastasis, the positive rate of bax overexpression was correspondingly increased. CONCLUSION: The results suggest that bax expression affects the balance between the endometrial cell proliferation and apoptosis. Bax might play an important role in carcinogenesis and tumor progression of endometrial carcinoma. As a high risk factor it can be used to evaluate the biological behavior of endometrial carcinoma. PMID- 11783090 TI - [CAG microsatellite polymorphisms of androgen receptor gene and the stage and grade of prostate cancer]. AB - OBJECTIVE: To explore the relationship between the CAG microsatellite in androgen receptor (AR) gene and the stage and grade of prostate cancer(PC). METHODS: The number of CAG repeats in exon 1 of the AR gene was measured in 37 PC tissues by PCR-SSCP analysis, and its association with stages and grades of PC determined. RESULTS: The average number of CAG repeats of AR gene differed significantly between PC in stage B (25.04 +/- 1.88) and in stage C-D (24.14 +/- 2.64) (P = 0.002). The frequency of short CAG(< 22) was 13.0% (3/23) in stage B and 28.6%(4/14) in stage C-D, while that of long CAG(> or = 22) was 87.0% (20/23) and 71.4% (10/14) (P = 0.029), respectively. The average number of CAG repeats increased with the decrease in tumor cell differentiation. The frequency of short CAG repeats dropped with the increase in tumor cell differentiation while the opposite was true for that of long CAG repeats. CONCLUSION: The number of CAG repeats in AR gene may be one of the factors determining the biologic characteristics PC. Short CAG repeats may signify aggressiveness of PC. PMID- 11783091 TI - [Detection of HPV in human esophageal cancer in high-incidence area and its correlation with p53 expression]. AB - OBJECTIVE: To investigate the association of HPV with the development of esophageal cancer (EC) in a high-incidence area of EC and to elucidate its correlation with p53 overexpression. METHODS: Thirty EC specimens were collected from Anyang, Henan. Four pairs of primers were designed to perform in situ hybridization (ISH) and in situ PCR(ISPCR). Immunohistochemical staining was used to detect p53. RESULTS: HPV L1, HPV-16-E6 and HPV-16-E7 was detected in 10.0%, 60.0% and 63.3% of the EC samples, respectively. The detection rate of HPV-18-E6 was low(6.7%) and no EBV was detected. Overexpression of p53 was identified in 73.3% EC. With ISH or ISPCR, HPV-16-E6 was positive in 53.3% of EC. CONCLUSION: The low detection rate of HPV L1 and high detection rate of HPV-16-E6 and E7 genes suggest that HPV may be partially lost when integrating into tumor cell genome, while E6 and E7 genes are intact. The results support a role of HPV-16 in the pathogenesis of EC in high incidence area. Although p53 mutation takes an important part in tumor pathogenesis, it is not consistent with the HPV existence in the EC cells. PMID- 11783092 TI - [Expression of nm23 in breast cancer: correlation with distant metastasis and prognosis]. AB - OBJECTIVE: To investigate the relationship between expression of nm23 gene and distant metastasis and prognosis in breast cancer. METHODS: To detect nm23 protein expression in 101 patients with breast cancer by means of immunohistochemistry and nm23 mRNA expression in 68 patients with breast cancer by RT-PCR. RESULTS: Expression of nm23 gene was inversely correlated with distant metastasis and lymph node metastasis. Among 9 patients with negative node but with distant metastasis, 7 had low expression of nm23. In 29 patients with positive nodes but without distant metastasis, 24 had high expression of nm23, while 6 of 6 patients with positive nodes and distant metastasis expressed high levels of nm23 mRNA. CONCLUSION: Expression of nm23 gene, tumor size and status of axillary lymph node are independent prognostic indicators to breast cancer prognosis. PMID- 11783093 TI - [Transrectal ultrasound examination of the prostate in 100 cases of prostate cancer]. AB - OBJECTIVE: To evaluate the clinical value of transrectal ultrasound (TRUS) examination of the prostate in the diagnosis of prostate cancer (PCA). METHODS: The sonographic and clinical data of 100 patients with PCA were analyzed retrospectively. RESULTS: There was single lesion in 59 patients, diffuse lesion in 17 patients. The size of tumor in 35 patients was < or = 1.5 cm. TRUS in the diagnosis of PCA had an accuracy of 76.0%, specificity of 89.4%, false positive rate of 10.6% and negative predictive value of 88.9%. The level of prostate specific antigen (PSA) increased with the increase in the size of the tumor (P < 0.05). The PSA level of patients with poorly differentiated PCA was significantly higher than that in patients with well differentiated PCA. CONCLUSION: TRUS examination is a convenient procedure for the diagnosis of PCA in its early stage. PMID- 11783094 TI - [The clinical usefulness of helical CT multiplanar reformation, three-dimensional reconstruction and virtual laryngoscopy in laryngeal and hypopharyngeal carcinomas]. AB - OBJECTIVE: To evaluate the clinical applications of helical CT multiplanar reformation (MPR), three-dimensional reconstruction (3D) and virtual laryngoscopy (CTVL) in laryngeal and hypopharyngeal carcinoma. METHODS: Axial helical CT scan was performed in 24 patients with laryngeal or hypopharyngeal carcinoma, meanwhile MPR, 3D and CTVL were performed on each patient. The results were compared with the fiberoptic laryngoscopic and surgical findings. RESULTS: Axial helical CT combined with MPR images, the accuracy of preoperative tumor staging and detection of metastatic lymph nodes were both 96%. In 25% of the cases, MPR was more informative than axial images about the extent of tumor invasion. The 3D image three-dimensionally displayed the extent of tumor invasion, and its relation to blood vessels and airway. On CTVL, the location, size and extent of intraluminal tumors of the larynx and hypopharynx when observed from above corresponded well with those observed under laryngoscope. In 4 patients, CTVL observed from below, demonstrated the relationship between the tumor and vocal cords and anterior commissure inaccessible to fiberoptic laryngoscopy. CONCLUSION: Helical CT axial scanning combined with MPR, 3D and CTVL images, can provide more comprehensive information about laryngeal and hypopharyngeal carcinoma. PMID- 11783095 TI - [Intraoperative ultrasonographic detection of liver metastasis from tumors of the digestive tract]. AB - OBJECTIVE: To ascertain the value of intraoperative ultrasonography to early detect liver metastasis from tumors of the digestive tract. METHODS: Intraoperative ultrasonography (US) of the liver was performed in 176 patients with confirmed diagnosis of cancer of the stomach and colon. All the nodules detected were either resected or needle biopsied for histological diagnosis. The results of the liver US were compared with those of pre-operative trans-abdominal US, CT scanning and intraoperative exploration. RESULTS: Liver metastasis was detected by intraoperative US in 43 of the 176 patients (24.4%), with a total of 81 nodules found. Liver metastasis was confirmed histologically in 42 of the 43 cases (97.7%), the frequency of which was significantly higher than that of preoperative transabdominal US, CT scan and surgical exploration (P < 0.05, P < 0.01). It was particularly superior for the detection of liver metastasis less than 2 cm in diameter. CONCLUSION: Intraoperative ultrasonography is sensitive enough to early detect tumors of the stomach and colon metastasized to the liver. PMID- 11783096 TI - [Pathological study of extracorporeally ablated hepatocellular carcinoma with high-intensity focused ultrasound]. AB - OBJECTIVE: To investigate the pathological changes of hepatocellular carcinoma (HCC) after extracorporeal ablation with high-intensity focused ultrasound (HIFU). METHODS: A total of 56 patients with HCC was treated with HIFU. Of the 56 patients treated, 6 underwent surgical resection of the tumor 5 to 18 days following HIFU treatment The resected specimens were examined under light and electron microscope. RESULTS: Light microscope examination showed clear boundary between the treated and untreated area. Outside of the boundary the hepatic parenchyma was almost normal. In the treated area, all tumor cells appeared irreversibly dead in the forms of nuclear pyknosis, debris, and dissolution. The blood sinusoids were collapsing with endothelial cell damage. Granulation tissue was formed with the presence of immature fibroblasts and new capillaries in the boundary region between treated and untreated area. Eighteen days after HIFU treatment, the ultrasound damaged area was partially replaced by the proliferative repair tissue. Electronic microscopic examination showed the distorted tumor cells with severe destruction of cell organelles and nuclei. The cytoplasm was irregularly vesiculated, and the membranes of the organelles were broken. Cell membrane and nuclear membrane disintegration, as well as nucleus disruption were generally observed. CONCLUSION: Extracorporeal treatment of HCC with HIFU proved safe, effective, and feasible. This modality could potentially provide a new and noninvasive therapy for HCC. PMID- 11783097 TI - [Multivariate analysis of prognosis of patients with stage IE non-Hodgkin's lymphomas of the nasal cavity]. AB - OBJECTIVE: To analyze the factors affecting prognosis of patients with primary non-Hodgkin's lymphomas (NHL) of the nasal cavity. METHODS: From Jan. 1968 to Dec. 1997, a total of 71 patients with stage IE(Ann Arbor staging system, 1971) primary non-Hodgkin's lymphomas of the nasal cavity were treated in the Tumor Hospital of Sun Yat-sen University of Medical Sciences. In 37 of the 71 patients, the lesions were limited in the nasal cavity (limited IE), and in 34, the lesions were locally extended involving the adjacent structures (extended IE) Forty-four patients were treated with radiotherapy and 27 with radiotherapy plus chemotherapy. Survival analysis was done by the Kaplan-Meier method, and multivariate analysis was carried out using Cox proportional hazard model. RESULTS: The 5- and 10-year survival rate was 71.9% and 59.7% respectively in patients who had complete response to radiotherapy. The 5- and 10-year survival rate was both 13.9% in patients who had residual tumors after treatment. The 5- and 10-year survival rate was 69.8% and 56.7% in patients with limited IE lesions, but 40.7% and 35.6% in those with extended IE lesions. The prognosis was better in younger (< 44 years) than in older patients. The 10-year survival rate of patients received radiotherapy alone and those combined with chemotherapy was 52.0% and 75.0% respectively for limited IE as compared to 37.6% and 45.0% for extended IE. B symptoms did not significantly affect clinical outcome. Multivariate analysis showed that the immediate response to radiotherapy, invasion of the primary tumor outside of nasal cavity and patients' age were independent prognostic factors. CONCLUSION: Radiotherapy is the main treatment method for stage IE non-Hodgkin's lymphoma of the nasal cavity. Addition of chemotherapy can improve long-term survival. The local tumor response to radiotherapy, clinical staging and age of patients have significant influence on patients' prognosis. PMID- 11783098 TI - [Prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma]. AB - OBJECTIVE: To explore the prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma (NPC). METHODS: From Jan. 1987 to Dec. 1994, 197 previously untreated NPC patients were examined by CT scan. The prognostic factors ware evaluated by univariate and multivariate analyses on SPSS 8.0 software. RESULTS: The actual survival rate, disease-free survival rate and local failure-free rate were negatively affected by the presence of parapharyngeal space involvement (P = 0.0115, P = 0.0035, P = 0.0367). The 5-year actual survival rate, disease-free survival rate and local failure-free rate in patients without tumor invasion to parapharyngeal space was 87.9%, 88.0% and 96.9%, respectively. The survival rate in patients with tumor invasion to prestyloid space was 75.0%, 71.2% and 93.7%, respectively. That in patients with tumor invasion to poststyloid space was 60.5%, 57.7% and 86.8%, respectively. The 5-year distant metastasis-free survival rate was 88.1% in patients without poststyloid involvement as compared to 73.8% in those with poststyloid involvement. CONCLUSION: The survival and local tumor control are affected by parapharyngeal space involvement. Distant metastasis is more likely to occur when the tumor growth involves poststyloid space. PMID- 11783099 TI - [Clinical significance of sentinel lymph node biopsy for breast cancer]. AB - OBJECTIVE: To study the significance of sentinel lymph node(SLN) biopsy (SLNB) in determining the extent of axillary dessection for cN0 breast cancer patients. METHODS: In 96 patients with cN0 breast cancer, sentinel lymph nodes identified by patent blue-V or methylene blue staining were excised for biopsy. patients then received operations for breast cancer including axillary dessection. RESULTS: SLN was identified in 91 patients. The total number of SLN identified was one in 54 cases(59.3%), 2 in 23 cases(25.3%) and > or = 3 in 14 cases(15.4%). In 24 of the 91 patients, SLN was positive for metastasis. In 13 the 24 patients, only SLN provided evidence of lymph node metastasis. The sensitivity of SLN biopsy was 87.5%, the specificity was 100%. It had 100% positive predictability and 95.7% negative predictability of lymph node metastasis. The accuracy rate of intraoperative imprint cytology examination of SLN was 92.1%, with a false negative rate of 10.0% and a false positive rate of 7.1%. The accuracy rate of frozen-section examination of SLN was 98.7% during operation, with a false negative rate of 5.0% but without false positive result. Immunohistochemical assay did not help demonstrate metastasis in SLN negative on routine pathologic examination. CONCLUSION: The SLN status can generally be a representation of axillary metastasis, SLNB is useful to determine the extent of axillary dessection in cN0 breast cancer patients. Methylene blue is as effective as patent blue-V in the identification of SLN. PMID- 11783100 TI - [The clinical effect of Tropisetron in the prevention of nausea and vomiting induced by anti-cancer drugs]. AB - OBJECTIVE: To compare the efficacy and adverse effects of Tropisetron with Kytril in the prevention of nausea and vomiting induced by anti-cancer drugs. METHODS: In a clinical randomized controlled cross-over trial, 34 patients (19 among them treated with regimens containing cisplatin) were randomized into A and B group. In group A, Tropisetron was given in the first cycle and Kytril in the second cycle, while in group B Kytril was given in the first and Tropisetron in the second cycle of the same chemotherapy. RESULTS: In the Tropisetron treated group, the response rate was 97.1% with 4.5 episodes of vomiting on the first day of chemotherapy, while that in the Kytril treated patients was 94.1% with 3 episodes of vomiting. There was no statistical difference between the 2 groups. Control of delayed emesis and other adverse reactions were comparable in both arms and there was no notable difference between Tropisetron and Kytril. CONCLUSION: Tropisetron is an effective anti-emetic drug to prevent nausea and vomiting caused by anti tumor agents, and its adverse reactions are mild. PMID- 11783101 TI - [A randomized clinical study of preoperative chemotherapy for esophageal carcinoma]. AB - OBJECTIVE: To evaluate the effect of preoperative chemotherapy on the prognosis of stage II or III patients with esophageal carcinoma. METHODS: From February 1991 to June 1994, 50 patients with stage II, III esophageal carcinoma were treated with preoperative combination (CDDP) chemotherapy and compared with 50 patients received operation alone. RESULTS: The 5-year survival rate of the operation group and preoperative chemotherapy group was 32% and 46%, respectively. The difference was statistically significant. CONCLUSION: Preoperative chemotherapy improves survival of surgically treated esophageal cancer patients. PMID- 11783102 TI - [Clinical and pathological characteristics of head and neck malignant melanoma]. AB - OBJECTIVE: To investigate the clinical and pathological characteristics of head and neck malignant melanoma. METHODS: Sixty-eight cases of head and neck malignant melanoma were reviewed. There were 33 patients with melanoma in the nasal cavity and oral cavity, 35 patients with melanoma in the skin. The age fastigium of the patients was from 41 to 60 years. Surgical specimens in 52 cases and biopsy specimens in 16 cases were studied pathologically. S-100, HMB45 and NSE were examined immunohistochemically. RESULTS: Histopathology studies showed that the cell morphology was pleomorphic as well as polymorphic both in shape and size of the cells. Immunohistochemical studies helped diagnosis as all of the 42 melanoma specimens were posture for S-100 and 90.5% positive for HMB45. In 52 of the 68 cases, the tumor was excised surgically, with additional radiotherapy in 13 cases or chemotherapy in 21 cases. Ten cases were treated with radiotherapy alone. In 56 patients followed-up, 12 survived for 5 years, including 9 cases of skin melanoma and 3 cases of nasal and oral melanoma. CONCLUSION: The histo pathological features of malignant melanoma vary significantly. Immunohistochemical staining helps diagnosis and differential diagnosis. The prognosis of malignant melanoma in nasal cavity and oral cavity is poor as compared to that in the skin of head and neck region. PMID- 11783103 TI - [Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer]. AB - OBJECTIVE: To ascertain if any difference exists in clinical characteristics between resected non-small cell lung cancer (NSCLC) with either skip or ordinary mediastinal lymph node metastases. METHODS: Among 176 patients with stage IIIAN2 disease between 1982-1994 treated in our hospital, 53 had no metastasis at the hilar lymph nodes [skip(+) group] while 123 had [skip(-) group]. To investigate the extent of nodal involvement, the mediastinal lymph nodes were divided into three regions. RESULTS: In the skip(+) group, mediastinal node metastasis was found in only one region in 49 of the 53 patients(92.4%), whereas 45 of the 123 patients(36.6%) from the skip (-) group revealed medinastinal metastasis at two or three regions The overall survival rate at 5 years after operation was 29.3% in the skip(+) group and 12.2% in the skip (-) group (P = 0.038). Furthermore, regarding patients with mediactint node metantion in one region, the skip(+) group had a better prognosis than the skip (-) group (32.1% vs 15.3%, P = 0.042). CONCLUSION: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease. PMID- 11783104 TI - [Increase of EGFR expression by Epstein-Barr virus LMP1 in nasopharyngeal carcinoma cells]. AB - OBJECTIVE: To investigate the effect of LMP1 on the expression of epidermal growth factor receptor (EGFR) in HNE2-LMP1 cells. METHODS: Stable transfectant HNE2 cell line expressing LMP1 (HNE2-LMP1) or its mutants (HNE2 del 187-351, HNE2 1-231, HNE2 1-187) were used as cell models. The expression of EGFR was detected by Western blot method. The characteristics of EGFR expression were analyzed when HNE2-LMP1 LMP1 cells were transiently transfected with TRAF1, 2, 3 or TRAF1, 2, 3 dominant negative mutants (DN-TRAF1, 2, 3). The growth characteristics of HNE2 LMP1 and vector controls were analyzed on serum-free media supplemented with EGF. RESULTS: Stable expression of LMP1 in HNE2 cells increased the expression of EGFR. LMP1 CTAR1 domain, being identical to the TRAF interaction domain, was essential to the induction of EGFR. The CTAR2 domain did not induce expression of EGFR. Overexpression of either TRAF1, 3 or an dominant negative mutant of TRAF1, 3 inhibited the expression of EGFR, while TRAF2 or negative mutants of TRAF2 did slightly so. In HNE2-LMP1 cells, LMP1 expression increased the proliferative response to EGF while the vector control cells exhibited very low level of viability and did not proliferate. CONCLUSION: The induction of EGFR by LMP1 CTAR1 may be an important component of EBV infection via an TRAF1, 2, 3 mechanism in the epithelial cells and may contribute to the development of epithelial malignancies such as nasopharyngeal carcinoma. PMID- 11783106 TI - [Activation of PKA pathway inhibits reactivity of human myeloma cell line-U266 to IL-6]. AB - OBJECTIVE: To study the effects of PKA pathway activation on the biological function and signal transduction of IL-6 in a human myeloma cell line-U266. METHODS: The effect of IL-6 on the growth of U266 cells was shown by MTT; electrophoretic mobility shift assay (EMSA) was used to detect the activation of two transcription factors(TFs)-STAT3 and the NF-IL-6 by IL-6, which were involved in the JAK/STAT and Ras/NF-IL-6 signal transduction pathways. Then, the cells were treated with IL-6 and Forskolin (FK), an agonist of the PKA pathway. The changes in the cell growth and activation of the two TFs were exhibited by MTT and EMSA. RESULTS: (1) IL-6 could promote the proliferation of U266 cells, (2) both JAK/STAT and Ras/NF-IL-6 signal transduction pathways were activated by IL-6 in the U266 cells and (3) Cell proliferation and activation of the two IL-6 signal transduction pathways were inhibited by Forskolin; down-regulating the actiration of these two signal transduction pathways at the same time. CONCLUSION: The inhibition of cell growth, mediated by the activation of the PKA pathway, is related to the down-regulated activation of the two IL-6 signal transduction pathways. PMID- 11783105 TI - [Gene apoptosis expression profiles in liver cancer and their comparison to normal peri-cancerous liver tissues]. AB - OBJECTIVE: To describe a few gene expression profiles related to apoptosis and to demonstrate their difference between the liver cancer and its adjacent normal tissues. METHODS: cDNA, labeled as a-32P dATP was synthesized from the total RNA of cancer and adjacent normal tissues and, then, hybridized individually with two identical array membranes of Atlas human cancer dDNA expression containing 588 known genes. The method involving gene-specific semi-quantitative reverse transcription in the polymerase chain reaction (RT-PCR) was used to confirm the expression pattern of three known genes. RESULTS: Autoradiographic results were analyzed by specific AtlasImage (version 1.01a) software. Among 69 genes that were found to be related to apoptosis, 4 were up-related, including Aktl, and 19 were down-related, including BAK, Caspase-3, etc., all being related to cancer. The RT-PCR results showed that the expression pattern of all genes was in agreement with the results of Atlas expression array. CONCLUSION: The result obtained from Atlas microarray provides a liver cancer-specific expression profile related to apoptosis. The discovery about the apoptosis related genes may yield some clues on the oncogenetic mechanism of liver cancer in the future. The differential hybridization technique of cDNA expression array involving the Atlas human cancer can become a useful method in the understanding of the development and progression of human cancer. PMID- 11783107 TI - [Differential display of vincristine-resistant proteins in gastric cancer cell line SGC7901]. AB - OBJECTIVE: To find out new multidrug-resistant proteins in gastric cancer cells SGC7901 and to explain the new multidrug-resistant mechanism of gastric cancer cells. METHODS: Two-dimensional gel electrophoresis was used with immobilized pH gradients (IPG) to compare the differential expression of multidrug-resistant proteins in gastric cancer cells SGC7901 and Vincristine-resistant SGC7901 cells (SGC7901/VCR) induced by vincristine sulfate. 2-D gels were used to silver stain the protein. RESULTS: Approximately, 680 protein spots were identified in each of the 2-D gel patterns by silver stain. With most of them showing no difference in composition, shape or density, twenty-five proteins were found to differ in quantity (6 higher in SGC7901/VCR cells; 19 higher in 7901 cells). Five proteins were seen to be unique in one region or the others (3 in SGC7901/VCR cells, 2 in 7901 cells). The coordinate position of 30 protein spots in the 2-D gels were listed. CONCLUSION: The results suggest that these differential proteins be related to the vincristine-resistant mechanism in human gastric cancer cell line SGC7901/VCR. PMID- 11783108 TI - [Bispecific McAb mediated multiple tumor cytotoxicity in gastric cancer]. AB - OBJECTIVE: McAb against CD3 and McAb against TNP were combined into bispecific McAb by chemical methods. With this bispecific McAb, human peripheral blood lymphocytes (PBLS) were introduced to in vitro and in vivo cytotoxic test of any tumor cells by different TNP-McAb against gastric cancer. METHODS: The activity of bispecific McAb prepared by chemical method, was detected by enzyme-linked immunosorbent assay (ELISA). The bispecific McAb was identified by bridge ELISA. Ouchterlony test and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Cytotoxic test of tumor cells in vitro and tumor growth inhibition test in vivo were performed for the bispecific McAb function. RESULTS: Anti-CD3 and Anti-TNP McAbs were successfully combined into bispecific McAb which could conjugate any TNP-McAb against gastric cancer and induce PBLS to cytotoxic test of gastric cancer cells in vitro and in vivo. CONCLUSION: The bispecific McAb may very will be useful in the immuno-biotherapy of tumors. PMID- 11783109 TI - [Relationship among telomerase activity, telomerase RNA and telomerase catalytic subunit gene expression and their significance in non small-cell lung cancer]. AB - OBJECTIVE: To study telomerase activity (TA), telomerase RNA (hTR) and telomerase catalystic subunit (hTRT/hEST2) code gene expression in non-small cell lung cancer (NSCLC), their relationship and significance. METHODS: Telomerase repeat amplification protocol PCR (TRAP-PCR) for TA, RT-PCR for hTR and in situ hybridization for hTRT/hEST2 mRNA expression were performed. RESULTS: Positive rates of TA, hTR and hTRT/hEST2 were 68.4%(26/38), 51.7%(32/58) and 74.2%(43/58) in NSCLC. But, the adjacent and benign lung tissues were negative for expression of TA, hTR and hTRT/hEST2. A statistically significant positive correlation between TA and hTRT/hEST2 was observed(r = 0.84, P = 0.01), though there was no statistically significant positive association between TA and hTR (r = 0.16, P = 0.23). The median survivals of TA and hTRT/hEST2 positive groups (10.4 months, 7.5 months) were shorter than the negative ones (13.5 months, 14.7 months). However, only the hTRT/hEST2 group was found to show statistical significance to be an independent prognostic factor by multivariate Cox regression analysis. CONCLUSION: Telomerase activity, hTR expression and hTRT/hEST2 are frequently detected at higher levels in NSCLC than the pericancerous normal tissues. There is a positive correlation between TA and hTRT/hEST2, both of which are markers of poor magnificent phenotype of NSCLC. The hTRT/hEST2 has an independent prognostic significance. PMID- 11783110 TI - [Alterations in DPC4 gene in pancreatic cancers]. AB - OBJECTIVE: To examine the alterations in the DPC4 gene in pancreatic cancers. METHODS: Five pancreatic adenocarcinoma cell lines (P1, P2, P3, P4, and P7) and 11 fresh frozen pancreatic cancer tissues were monitored with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) analysis to demonstrate the sequence of deletion and mutation in 6 exons (1, 2, 3, 4, 8, and 11) of the DPC4 gene. RESULTS: Mutation in the DPC4 gene was found in 3 of 5 cells lines (P1, P2, and P3). Three of eleven fresh-frozen tissues showed homozygous deletions and two showed intragenic mutations, with a gene alteration frequency of 45.5% (5/11). CONCLUSION: Alterations in tumor-suppressor gene DPC4 may play an important role during the tumorigenesis of pancreatic cancer. PMID- 11783111 TI - [Suppression subtractive hybridization in the cloning of gene fragments in relation to lung cancer metastasis]. AB - OBJECTIVE: In order to provide important information about early diagnosis and treatment of tumor metastasis, a study on the biological regulation of metastasis at the molecular level was carried out by isolating and identifying human metastatic suppressor gene or related DNA sequences from a pair of cell clones with different metastatic phenotypes. METHODS: Suppression subtractive hybridization technique (SSH), gene cloning and analysis by bioinformatics were applied to this study. Two cell clones of pulmonary giant cell carcinoma originating from the same patient were used. The PLA-801C cell clone which shows lower metastatic potentiality was used as tester and the PLA-801D as a driver. RESULTS: Five cDNA clones so obtained were expressed on much higher levels in the poorly metastatic cancer cell clone than the highly metastatic one. Homology analysis of all five cDNA fragments by BLASTN through GenBank showed high homology with the known human genes. CONCLUSION: Through using SSH, we have identified five cDNA fragments which are expressed at much higher levels in the poorly metastatic cancer cell clone than the highly metastatic variety. Therefore, it is supposed that they might play an important role in the suppression of metastatic tumor cells and may very well have potential application in the diagnosis and treatment of metastasis. PMID- 11783112 TI - [Correlation between the biological behavior and invasion potential in three mouse melanoma cell lines]. AB - OBJECTIVE: To study the correlation between biological behavior and invasion potential in three homologous mouse melanoma cell lines (B16, B16F10, B16BL6). METHODS: The invasion potential of melanoma cells was assayed in a Transwell cell culture chamber. Melanin content was determined by the A value (optical density) at 470 nm in spectrophotometry. Tumor cells migration within the 3-D collagen matrix was microscopically recorded with a time-lapse video recorder and computer assisted cell tracking system. Gelatin zymography was adopted to assay the type IV collagenase secretion. A PCR-based telomeric repeat amplification protocol (TRAP) was used for assaying telomerase activity. RESULTS: B16BL6 and B16F10 cells showed higher invasion potential than B16, but the melanin content in B16F10 was very low. B16F10 and B16BL6 possessed a higher migration ability, secreting much more type IV collagenase than the B16 though without significant difference as discovered in telomerase activity of the three melanomas cell lines. CONCLUSION: Invasion capability of mouse melanoma is closely correlated to tumor cells migration ability and secretion of type IV collagenase. Melanin content and telomerase activity are not related to the invasion ability of mouse melanoma cells. PMID- 11783113 TI - [Comparison of stepwise and pulse induced cisplatin-resistant ovarian cancer cell sublines]. AB - OBJECTIVE: To investigate the mechanism responsible for acquired cisplatin resistance induced in human ovarian cancer cell lines by different methods. METHODS: Two resistant cell lines, Skov3/CDDP-P and Skov3/CDDP-50, were established by pulse or stepwise exposures of ovarian cancer cell line Skov3 to cisplatin (CDDP) for 10-12 months with the drug sensitivity monitored by MTT test. The growth rate and cell cycle were compared. The intracellular drug concentration was measured by FACS after 1 hour incubation in 20 mumol/L ADM. The drug-resistance-associated genes: MDR1, MRP, LRP and GST-pi were monitored by RT PCR and western blotting. RESULTS: The resistance indexes (RI) of Skov3/CDDP-P and Skov3/CDDP-50 were 3.7 and 48.6 to cisplatin, 4.0 and 33.0 to Taxol, 2.2 and 7.3 to adriamycin, 1.5 and 3.4 to VP16, and the intracellular ADM concentration was lowered by 34.6% and 47.2% respectively. Both resistant cell lines grew slowly and exhibited changes in morphology and cell cycle. The expression of the resistance-associated genes MDR1, MRP and LRP was enhanced in both resistant cell lines. However, Skov3/CDDP-50 showed greater increase in MDR1 but Skov3/CDDP-P showed more in MRP. There were no significant changes in GST-pi expression either at mRNA or protein level. The TOPO II activity decreased slightly in both resistant cell lines. CONCLUSION: Stepwise induction of cisplatin resistance in ovarian cancer is more readily acquired in which multiple drug-resistance associated genes are involved. PMID- 11783114 TI - [Comparative study on liquid-based cytology for cervical carcinoma screening in a high-risk area of China]. AB - OBJECTIVE: To evaluate the efficacy of liquid-based cytology (ThinPrep Pap Test) for cervical carcinoma screening in a high incidence area, Xiangyuan county of Shanxi province. METHODS: This study was performed on 1997 women residing in Xiangyuan county, a high incidence of cervical carcinoma. Exfoliative cervical samples and subsequent colposcopic biopsies were taken from all subjects. Cervical samples were collected into a liquid buffer for both ThinPrep Pap Test cytologic screening and human papilloma virus (HPV) DNA test. All tests were carried out independently and blindly of which the results were compared with those of HPV DNA detection and colposcopic biopsies. RESULTS: When the cytologic diagnosis of atypical squamous cells of determined significance (ASCUS) was taken as the detection threshold and compared with the "standard" biopsy, the ThinPrep slides were able to detect 100%(12/12) of squamous cell carcinoma (SCC) and 93.2% high grade squamous intraepithelial lesions (HSIL) which included 96.8% (30/31) CIN III, 90.7% (39/43) CIN II and 72.4%(92/127) low grade squamous intraepithelial lesions (LSIL). When cytologic diagnosis of HSIL was used as the detection threshold, the ThinPrep slides were able to detect 100% (12/12) SCC and 87%(27/31) CIN III. CONCLUSION: Cervical specimens collected into a liquid buffer are suitable for both cytologic screening and human papilloma virus test. The ThinPrep cytology demonstrates a high sensitivity for the detection of high grade squamous intraepithelial lesions and squamous cell carcinoma. PMID- 11783115 TI - [Value of P-glycoprotein and glutathione S-transferase-pi as chemo-resistant indicators in ovarian cancers]. AB - OBJECTIVE: This study was conducted to assess the predictive value of P glycoprotein (P-gp) and glutathione S-transferase-pi(GST-pi) as indicators of resistance to chemotherapy in ovarian cancers. METHODS: Expressions of P-gp and GST-pi were immunohistochemically studied in paraffin sections from 30 normal ovaries and 74 resected specimens of primary epithelial ovarian cancer from patients who had not received any chemotherapy before surgery. RESULTS: There were no detectable P-gp or GST-pi expression in the 30 patients with normal ovaries. In 74 cases of ovarian cancer tissue, P-gp was positive in 14 (18.9%) and GST-pi positive in 55 (74.3%) showing a highly significant correlation (P < 0.01). However, expression of P-gp and GST-pi was not associated with any of the clinicopathological parameters, such as clinical stage, histologic or tumor grade (P > 0.05). The evaluation of chemotherapy for postoperative residual ovarian cancer patients showed that all the six lesions showing P-gp positive were drug resistant whereas only nine of the twenty-one tumors showing negative results were drug-resistant. Of 27 clinically measurable resected lesions, this difference in the response rates of the two groups was significant (P < 0.05). The predictive value of positive P-gp stain for drug resistance was 100% (6/6), and that of negative stain for objective responders was 57.1%(12/21). The response rate to chemotherapy of the GST-pi positive group (13.3%-2/15) was significantly lower than that of the SGT-pi negative group (83.3%-10/12, P < 0.01). The predictive value of positive GST-pi stain for drug resistance was 86.7%(13/15) and that of negative stain for objective responders was 83.3%(10/12). The survival rates of P-gp negative and GST-pi negative tumor patients were significantly higher than those of P-gp positive and GST-pi positive tumor patients (P < 0.01, P < 0.05, respectively). CONCLUSION: These data suggest that P-gp and GST-pi expression in tumor cells are related to drug resistance in epithelial ovarian cancer. They are useful indicators of resistance to chemotherapy. PMID- 11783116 TI - [Mammaglobin mRNA measurement in the detection of micrometastasis in peripheral blood of breast cancer patients]. AB - OBJECTIVE: To investigate mammanglobin (hMAM) mRNA as a marker for the detection of carcinoma cells by reverse transcriptase chain reaction (RT-PCR) in the peripheral blood of breast cancer patients. METHODS: Blood samples from 63 breast cancer patients obtained at various stages of their disease, blood samples from 8 breast hyperplasia, 5 breast adenofibroma, 25 other cancers (stomach, colon, esophagus, lung, ovary) and 31 healthy volunteers were screened for hMAM mRNA by a nested RT-PCR combined with fluorescence quantitative PCR (FQ-PCR) assay. RESULTS: Among 63 breast carcinoma patients, 19(30.2%) were RT-PCR positive for hMAM mRNA which was elevated with the tumor stage. None of the other cancer patients or those suffering from benign breast diseases were positive but only 1 of the 31 healthy volunteers gave detectable hMAM mRNA findings. hMAM mRNA was not detectable in the peripheral blood after operation in 6(32%) of 19 patients whose pre-operative test had been positive even though the hMAM mRNA expression increased with tumor stage. These results did not correlate with patients' stage, estrogen or pregnant receptor status. CONCLUSION: hMAM transcripts are detectable in the peripheral blood of some breast cancer patients. hMAM may be a novel candidate and a clinically useful breast tumor marker, especially in detecting micrometastasis. PMID- 11783117 TI - [Correlation between cell-functional differentiation phenotype and pathobiological behavior of gastric carcinoma]. AB - OBJECTIVE: To demonstrate the correlation between cell-functional differentiation features and invasion, metastasis of gastric carcinoma (GC) by establishing a new classification based on cell-functional differentiation. METHODS: According to the direction and condition of cell-functional differentiation, 361 gastric carcinomas were divided into five types to show their respective pathobiological behavior. RESULTS: (1) Absorptive functional differentiation type (AFDT): 22.7%(82). 13.6% of the male patients developed liver metastasis, (2) Mucin secreting functional differentiation type (MSFDT): 15%(54). 98.1% of GC showed serosa invasion, (3) Absorptive and mucin-producing double functional differentiation type (AMPFDT): 49.9% (180). Women infliction (34.4%) and estrogen receptor (ER) expression (71.7%) in this group were more common than in the other types (P < 0.01). 19.4% of these female patients were complicated with ovarian metastasis, (4) Specific functional differentiation type (SFDT): 3.6%(13). 69.2% of these tumors derived from (high) A (amine content) + (high) P (precursor) U (uptake from the ambient medium) + (presence of) D (decarboxylase) (APUD) system and (5) non-functional differentiation type (NFDT): 8.9%(32). 59.4% developed lymphatic metastasis. The 5-year survival rates of these types were 58.5%, 28.6%, 24.7%, 60.0% and 28.1%, respectively. CONCLUSION: This new cell-functional classification of gastric cancer is helpful by indicating their pathobiological behavior and characteristics of invasion and metastasis. Further study is needed to clarify the correlation between cell-functional differentiation phenotypes and their relevant genotypes as well as the inherent relationship between the biological behavior. PMID- 11783118 TI - [Clinico-pathologic study on extended radical resection for rectal cancer]. AB - OBJECTIVE: To justify clinico-pathologically the extended radical resection for rectal cancer. METHODS: Resected lymphatic specimens obtained by the triple approach in the radical resection for advanced rectal cancer was studied by routine pathological method. The outcome of this extended radical resection, guided by the route of lymphatic metastasis are presented in the justification. RESULTS: The incidence of lymphatic metastasis in advanced rectal cancer in the Chinese was 45.0%, with 44.0%, 14.0%, 10.0% and 9.0% in the upper 1, 2, 3 and the lateral third groups. Lymphatic metastasis from rectal cancer was related to the extent, depth and pathological type. The 5- and 10-year survival rates were 68.0% and 47.0%, which are much higher than those of the conventional radical resection. CONCLUSION: Extended radical resection for the rectal cancer, removing all the lymphatics, is able to prevent possible metastasis, thereby improving the survival rate significantly, This extended radical resection is an optimal type of operation. PMID- 11783120 TI - [Transcatheter arterial chemoembolization for postoperative residual tumor of hepatocellular carcinoma]. AB - OBJECTIVE: To understand and analyze the survival and prognostic factors of postoperative residual tumor of hepatocellular carcinoma treated by transcatheter arterial chemoembolization. METHODS: Transcatheter arterial chemoembolization was performed in 74 patients who were identified as having residual lesions by ultrasonography, hepatic arterial angiography or enhanced computed tomography about two months after resection of hepatocellular carcinoma. Kaplan-Meier method was used for survival and Cox regression model for prognostic factors. RESULTS: The 1-, 2- and 3-year survival rates were 78.0%, 57.6%, 37.0%, with a median survival of 33 months. Univariate analysis indicated that a primary tumor over > 5 cm in diameter, vascular involvement by the primary tumor and TNM extent of the residual lesion were important factors indicating a bad prognosis, where as the combination of other treatment methods such as percutaneous ethanol injection (PEI), and/or radiotherapy indicated a better prognosis. However, multivariate analysis showed that vascular involvement by the primary tumor and the other combined local treatments were independent factors of prognosis. CONCLUSION: Transcatheter arterial chemoembolization is effective in treating the postoperative residual tumor of hepatocellular carcinoma. Further improvement is observed if combined with other local therapies such as percutaneous ethanol injection or radiotherapy. PMID- 11783119 TI - [p53 and vascular endothelial growth factor expression in astrocytoma and their relation to angiogenesis]. AB - OBJECTIVE: This investigation was done to show the pathological importance of p53 protein detection, vascular endothelial growth factor expression (VEGF) and intratumoral microvessel density (IMVD) in astrocytoma. METHODS: The surgical specimens from 60 brain astrocytoma patients were stained immunohistochemically for p53 and IMVD expressions. IMVD was calculated by labeling the endothelial cells of the blood vessels within the tumor. RESULTS: p53, VEGF expression were closely correlated with histopathological grade of astrocytoma. Positive p53 protein accumulation and VEGF expression were found in 45.0% (27/60) and 65.0% (39/60) of tumors. The conformation rate of p53 and VEGF was 70.0% (42/60). IMVD was significantly higher in the p53-positive or VEGF-positive tumors than in the negative ones (P < 0.05). Comparing the IMVD in p53+/VEGF+ group, p53-/VEGF+ group and p53+/VEGF- group, p53-/VEGF- group, its difference was also highly significant (P < 0.05). CONCLUSION: (1) p53 protein detection, VEGF expression and IMVD can be considered as a biological indicator of malignant potential in brain astrocytoma patients and (2) p53 and VEGF expressions, both contributing to the tumor neovascularization, may be helpful in the understanding of intra tumoral angiogenetic mechanism in the future. PMID- 11783121 TI - [Treatment of stage II non-Hodgkin's lymphoma: analysis of 268 patients]. AB - OBJECTIVE: To seek the optimum treatment for patients with stage II non-Hodgkin's Lymphoma (NHL). METHODS: 268 patients with stage II NHL, treated from January 1987 to December 1993, received radiation alone (R-50), radiation plus chemotherapy (R + C - 73), chemotherapy followed by radiation then by chemotherapy (C + R + C - 72), chemotherapy plus radiation (C + R - 61) or chemotherapy alone (C-12). A total of 206 patients was treated with combined treatment. RESULTS: The 1-, 2-, 3-, 4-, 5- and 6-year survival rates were 95.1%, 87.8%, 87.8%, 85.4%, 82.9%, 53.6% in C + R + C group for patients with stage II high grade NHL, which were much better than those in the R group, R + C group and C + R group (P < 0.01). For patients with stage II intermediate grade NHL, the 1 , 2-, 3-, 4-, 5- and 6-year survival rates were 89.3%, 75.0%, 67.8%, 60.6%, 57.1%, 46.4% in the C + R + C group, which were better than those in the R group, R + C group and C + R group (P > 0.05). However, for patients with low grade NHL, the survival rates were similar both in the R group and the combination groups. CONCLUSION: For patients with stage II intermediate and high grade NHL, combination therapy of C + R + C is recommended. Radiation alone can only be used for patients with stage II low grade NHL. PMID- 11783122 TI - [Surgical management for colon cancer complicated with acute obstruction]. AB - OBJECTIVE: To evaluate the feasibility of tumor resection and stage-I anastomosis for colon cancer complicated with acute obstruction. METHODS: Seventeen colon cancer patients complicated with acute obstruction admitted from 1994-1998 into our hospital, together with 1,872 cases collected from 40 reports published in the same interval in China, a total of 1,889 cases were analyzed as to the results of their surgical management. RESULTS: In the whole group, there was an incidence of 3.1% anastomotic leak, 6.6% wound infection and 1.1% pulmonary infection. Ninety-three patients died of operation with an operation mortality of 4.9%. Postoperative 5-year survival rate was 26.0%-48.0% in patients with stage-I operation. It was 20.0%-38.0% in staged operation. CONCLUSION: Tumor resection with stage-I anastomosis for colon cancer complicated with acute obstruction is acceptable giving relatively satisfactory results. Technique, bowel cleansing during the operation, rational use of antibiotics and adherence to proper indications are crucial for stage-I operation. PMID- 11783123 TI - [Second primary lung cancer in laryngeal cancer patients: report on 36 cases]. AB - OBJECTIVE: To discuss the development, treatment and prognosis of a second primary lung cancer in laryngeal carcinoma patients. METHODS: A total of 36 patients with a second primary lung cancer was discovered in 2,182 laryngeal cancer patients. For comparison, a group of 15,541 lung cancers was also reviewed for the presence of a second primary laryngeal cancer. All patients have been followed for over five years. RESULTS: From 1958 to 1999, out of 2,182 laryngeal carcinoma patients, 36 synchronous (3) or metachronous (33) second primary malignancies of the lung were found. This represented 1.65% of all largngeal cancers observed or 45.0% of all the second primary cancers developed. Their pathology was: squamous cell carcinoma (32-88.9%), adenocarcinoma(2-5.6%), small cell carcinoma(1-2.8%) and large cell carcinoma (1-2.8%). The c-TNM stages were: stage I (7-19.4%), stage II (12-33.3%), stage III (9-25.0%) and stage IV (8 22.2%). The 2- and 5-year survival rates were 41.7% and 8.3%, with an average survival of 23 months. The interval from the treatment of the initial laryngeal carcinoma to the development of the new second primary carcinoma of lung ranged from 1 to 14 years, with an average of 44 months. CONCLUSION: Synchronous or metachronous second malignancies of the lung are sometimes encountered in laryngeal cancer patients while the occurrence of a laryngeal second primary following a lung cancer is not observed. The development of the second primary lung cancer is not related to the treatment of the initial laryngeal malignancies. Surgery plus external radiotherapy provides better results than surgery or radiotherapy alone. PMID- 11783124 TI - [Bronchioloalveolar carcinoma: a retrospective analysis of 52 patients]. AB - OBJECTIVE: To present the treatment and prognosis of bronchioloalveolar carcinoma (BAC). METHODS: A retrospective study was conducted on 52 bronchioloalveolar carcinoma patients admitted from April 1990 to April 2000 with emphasis on clinical manifestations, treatment and survival. All lesions were pathologically proved as either localized or diffused type. RESULTS: These 52 cases comprised 2.5% lung tumors treated in the same period. Its clinical symptoms were similar to those of the other lung cancers. Short of breath and positive physical chest findings were more common in the diffused type. Forty-seven of these 52 patients underwent surgery and 5, chemotherapy. Follow-up showed that 28 (53.8%) patients have died; 10 (19.2%) of recurrence and 18 (34.6%) of metastasis with a median survival of 24.3 months for the localized type and 5.3 months for the diffused type (P < 0.05), The median survival of stage II BAC was 26.8 months in contrast of 42.5 months of stage II non-BAC adenocarcinoma group(P < 0.05). However, there was no significant difference in the overall survival rates of BAC and non-BAC squamous carcinoma (P > 0.05). Even though, trend analysis still showed that there is a tendency of decline in the survival rates from squamous cancer, non BAC and BAC though (P < 0.05). CONCLUSION: Localized BAC gives a better prognosis than diffused BAC of which the biological characteristics are different from those of the non-BAC. Compared with the non-BAC, a more active postoperative treatment should be considered for the BAC patients, such as postoperative chemotherapy and or radiotherapy, especially for stage II BAC lesions. PMID- 11783125 TI - [Detection of transfusion transmitted virus infection and genotypes in pregnant women]. AB - OBJECTIVE: To clarify the frequency, the routes of transmission from mother to infant, the correlation factors and distribution of genotypes of transfusion transmitted virus (TTV) infection. METHODS: Nested-polymerase chain reaction (n PCR) was performed to detect TTV DNA and genotypes in serums and breast milks from 160 cases of pregnant women. RESULTS: TTV DNA in serum and breast milk was detected in 64 (40.0%) and 60 (37.5%) of 160 cases of pregnant women respectively. The positive rates of TTV DNA from HBV markers (+) and normal groups were 50.0%, 43.1% and 13.6%, 22.7% respectively in serums and breast milk. There were significant difference between the two groups (P < 0.05). The TTV genotypes were type I in all 124 samples of TTV DNA detected. CONCLUSIONS: TTV infection is common in the pregnant women and a high prevalence of TTV infection in pregnant women with positive HBV markers has been demonstrated. TTV infection is correlated with HBV. TTV is probably transmitted from mother to their children by breast feeding. All of TTV genotypes detected in pregnant women is genotype I. PMID- 11783126 TI - [Transfusion transmitted virus infection in mother-to-infant transmission]. AB - OBJECTIVE: To investigate the perinatal infection of transfusion transmitted virus (TTV) in the mother-to-infant transmission and molecular evidence. METHODS: TTV was examined in serum from 104 mothers and umbilical blood of their infants by a semi-nested polymerase chain reaction technique. TTV nucleotide sequences isolated from two sets of mother/infant pairs were analyzed. RESULTS: The TTV detection rate was 13.46% (15/104), and it was 4.81% (5/104) in the umbilical blood of their newborns. Homology analysis was done by sequencing between positions 1,915 and 2,185 of the published TTV genome, Analysis of TTV sequences from the 2 pairs of mother and infant both infected confirmed a genetic link between the virus of the infected mother and their infected infants. CONCLUSIONS: There is a possibility of vertical maternal-fetal transmission of TTV. PMID- 11783127 TI - [Study on infection of transfusion transmitted virus in serum, breast milk of pregnant women and umbilical venous blood from their newborns]. AB - OBJECTIVE: To study transfusion transmitted virus (TTV) infection in pregnant women and their newborns, and the route of transmission. METHODS: Serum, breast milk from 150 pregnant women and umbilical venous blood from their newborns were collected. TTV DNA was amplified by semi-nested-polymerase chain reaction, and the positive products were sequenced directly. RESULTS: The positive rate of TTV DNA in pregnancy serum was 11.3% (17/150). Among the 17 serum positive cases, TTV DNA was detected in 11 breast milk samples, and none in all the umbilical blood. The homologous of partial nucleotide sequence of TTV DNA between the 3 serum samples and their breast milk were 97.6%-99.2%. Compared the 5 serum positive samples (A1-A5) with N22 segments of Japanese original isolate, the homologous of partial nucleotide and amino acid sequence were 71.5%-92.8%, 71.5%-92.8%, respectively. CONCLUSION: There exists TTV infection in pregnancy serum and breast milk. Transmission by breast feeding may be one of the main pathway causing TTV infection. PMID- 11783128 TI - [Clinical analysis of idiopathic thrombocytopenic purpura with pregnancy]. AB - OBJECTIVE: To study the optimal management of pregnant women with idiopathic thrombocytopenic purpura (ITP). METHODS: The outcomes of 37 pregnancies with ITP about 10 years from (1990 to 1999) were analysed. RESULTS: Among the 37 cases, vaginal delivery and cesarean section were done in 16 and 21 cases respectively. Neonatal thrombocytopenia was diagnosed in 3 newborns. None of them had intracranial hemorrhage. The incidences of postpartum hemorrhage and infection were 8.1% and 2.7%, respectively. No maternal mortality was noted. CONCLUSIONS: In view of very low morbidity in babies of ITP mothers, we suggest that they be delivered vaginally if there is no obstetrical complications. Selected cesarean delivery should be performed in severely thrombocytopenic cases when there are sufficient fresh blood and platelet. The invasive interventions should not be used to avoid newborn thrombocytopenia. PMID- 11783129 TI - [Placental expression of epidermal growth factor receptor in pregnancy induced hypertension]. AB - OBJECTIVE: To clarify the expression of epidermal growth factor receptor (EGFR) in placenta from women with pregnancy induced hypertension (PIH). METHODS: EGFR of placenta was determined by immunohistological method and compared between normal pregnancies (34 cases) and pregnancies accompanied by PIH (30 cases). RESULTS: Positive immunostain of EGFR was located on cytoplasm, and membrane of syncytiotrophoblast and a small part of cytotrophoblast. Compared with that of normal pregnancy, the expression of EGFR in placenta from pregnancies complicated with PIH decreased significantly (P < 0.05). No significant differences of EGFR expression in placenta were found among women with mild, moderate and severe PIH (P > 0.5). No significant correlation was found between expression of EGFR and neonatal birthweight, placental weight (P > 0.01, for both). CONCLUSION: Decreased expression of placental EGFR was found in women with PIH, and that may play a role in the pathogenesis of PIH. PMID- 11783130 TI - [Non-invasive prenatal diagnosis of fetal Down syndrome by dual-color fluorescence in situ hybridization with co-denaturation]. AB - OBJECTIVE: To explore the possibility of non-invasive prenatal diagnosis of Down syndrome by dual color fluorescence in situ hybridization with co-denaturation. METHODS: Fetal nucleated red blood cells labeled by anti-glycophorin a monoclonal immunomagnetic microbeads were enriched from maternal peripheral blood by magnetic activated cell sorting. The ploidy of chromosome 21 and sex of fetuses were determined using two-color fluorescence in situ hybridization with 21 and Y chromosome probes denatured by codenaturation. The accuracy of prediction was verified according to the karyotype of fetuses by analysis of amniotic cells. RESULTS: The ploidy of chromosome 21 of fetuses from 11 pregnant women was predicted normal. The results were correctly identified by the fetal karyotypes. 5 pregnant women were predicted carrying male fetuses. The number and mean number of male fetal nucleated red blood cells were 9-65 and 25 per 2 ml, respectively. The purity of male fetal erythrocytes enriched from maternal peripheral blood was 1.4%-18.8%; 6 pregnant women were predicted carrying female fetuses, and no male fetal nucleated red blood cell was found. The results of sex prediction were consistent with the kayotypes of fetuses by analysis of amniotic cells. CONCLUSION: It is possible to predict the ploidy of chromosome 21 and the sex of fetuses when fetal nucleated erythrocytes enriched by direct immunomagnetic labeling followed by magnetic activated cell sorting are analyzed using two-color fluorescence in situ hybridization with Y and 21 chromosome probes through codenaturation. PMID- 11783131 TI - [Combining transvaginal sonography and endometrial cytology in the diagnosis of endometrial disorders in postmenopausal women]. AB - OBJECTIVE: To evaluate the combined use of transvaginal sonography and endometrial cytology for the diagnosis of endometrial disorders in postmenopausal women. METHODS: One hundred forty-three patients with postmenopausal uterine bleeding were studied prospectively. Transvaginal sonography was used to measure the endometrial thickness (double layers), followed by use of the ori endometrial sampler. The results were compared to the histopathologic diagnosis of specimens obtained by dilatation and curettage. RESULTS: When the cutoff point of endometrial thickness was set at 5 mm to detect endometrial malignancy and premalignancy, transvaginal sonography showed a 100.0% sensitivity and 56.9% false positive rate. Endometrial cytology showed a 96.3% specificity but it had a 2.5% false negative rate. The combined use of transvaginal sonography and endometrial cytology can decrease false positive rate of transvaginal sonography from 56.9% to 43.2% (P < 0.01). CONCLUSION: The combined use of transvaginal sonography and endometrial cytology is a good method to screen endometrial malignancy and premalignancy. PMID- 11783132 TI - [Relationship between estrogen receptor genotypes and female bone mineral density]. AB - OBJECTIVE: To observe the relationship between polymorphyism of estrogen receptor (ER) gene and bone mineral density (BMD) in women. METHODS: Seventy-eight postmenopausal women, 23 perimenopausal women, and 52 young women (aged 25-35 years) were enrolled into the study. BMD was measured by dual energy X-ray absorptiometry at lumbar spine, proximal femur, fore-arm and total body. We also examined the restriction fragment length polymorphism of the polymerase chain reaction product (PCR-RFLPs) of the ER gene with XbaI or PvuII enzyme in these women. RESULT: There was no significant relationship between RFLP by PvuII or XbaI and BMD in 78 postmenopausal women. In young healthy women, the mean BMD at Ward triangle of genotype pp (0.823 +/- 0.095) g/cm2 was higher than that of genotype PP greater trochanter(0.665 +/- 0.071) g/cm2(P = 0.037). The BMD at total body, lumbar, hip, trochanter, and Ward of genotype xxpp were significantly higher than those of other genotypes (P < 0.05). But such differences were not found in postmenopausal women. CONCLUSION: The genotype xxpp might indicate a higher BMD at total body, lumbar, hip, greater trochanter, and Ward in young women. There is no significant effect of ER genotype polymorphism defined by PvuII or XbaI on BMD in postmenopausal women. PMID- 11783133 TI - [Observation of preventing of bone loss during early postmenopause by percutaneous estradiol in Chinese postmenopausal women]. AB - OBJECTIVE: To investigate the optimal regimen for application of percutaneous estradiol gel in preventing bone loss in Chinese postmenopausal women. METHODS: A 3-year open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA). Sixty healthy women (naturally menopause for 1 to 5 years) were recruited and divided into four groups according to estrogen dosage and two kinds of progestin. All were given for 25 d/month. The cortical bone mineral density (BMD) of right radius was measured by single photon absorptiometry. The trabecular BMD in lumbar vertebrae was measured by quantitative CT. The spine and hip BMD were also measured by dual energy X-ray absorptiometry at baseline, 6, 12, 18, 24 and 36 months, respectively. The bone metabolic markers, scores of menopausal symptoms were also evaluated. RESULTS: Fifty-nine patients (98%) completed 1 year and 56 patients (93%) 2 years, 51 (85%) 3 years of study. The symptoms were alleviated by 80% after 6 months treatment on average. By the end of 24 month, the mean increases of BMD ranged from 4.3% to 7.5% in trabecular bone, and by the end of 36 month 4.2% to 6.2% in the lumbar (L) 2-4, 1.6% to 3.8% in the femur neck, with significant differences (P < 0.05). Comparing the 4 groups with each other, no significant differences (P > 0.05) were found in improvement of symptoms, bone markers and BMD. CONCLUSIONS: Both daily estrogen containing 0.75 mg and 1.5 mg E2 are effective to prevent the early postmenopausal bone loss and improve the menopausal symptoms. During 3 years treatment, the BMD of lumbar increased continuously and the BMD of hip increased in the first 2 years and then plateau. PMID- 11783134 TI - [Effects of ovulation induction on expression of integrins alpha 4 beta 1 in endometrium]. AB - OBJECTIVE: To study the effect of clomiphene citrate (CC) and human menopausal gonadotropin (hMG) on the expression of integrins alpha 4 beta 1 during implantation window in endometrium. METHODS: Endometrium integrin alpha 4 beta 1 expression was detected by immunohistochemistry method in the mid-secretory phase of 48 normal natural cycles. CC + hCG or CC + hMG + hCG cycles in 30 polycystic ovary syndrome (PCOS) patients and 48 normal women. RESULTS: The expression of endometrial integrin alpha 4 beta 1 was stronger in the natural cycles than those of ovulation induction cycles with CC + hCG or CC + hMG + hCG. So was the pregnancy cycles as compared with the non-pregnant cycles. CONCLUSION: The endometrial receptivity in the min luteal phase and pregnant rate declined during ovulation induction by CC + hCG or CC + hMG + hCG in either normal women or PCOS patients. PMID- 11783135 TI - [Prevention and management of severe hemorrhage during gynecological operations]. AB - OBJECTIVE: To investigate the prevention and management of severe bleeding during gynecological operations. METHODS: A retrospective study of 85,505 gynecological operations from 21 hospitals in China during the period of 1990-1999 was analyzed. RESULTS: There were 683 cases with bleeding more than 1,000 ml during surgery, an incidence of 0.80% (range 0.07%-6.98%). Operation for removal of malignant ovarian tumor was the commonest cause of severe bleeding (42.31%); followed by cervical carcinoma (28.71%); endometrial carcinoma (16.11%). Only 6 transvaginal surgeries (0.88%) had severe bleeding. The most common site of bleeding was massive oozing from the raw wound surface, then the paracervical area (15.7%), around sacral ligament (12.14%). CONCLUSIONS: Advanced malignant tumors, tumors located at retroperitoneal or with extensive adhesion were the main causes of profuse bleeding during operation. Good surgical skill and well understanding of the pelvic anatomy are the basic key points for surgeons, and a supportive anesthesia is also important in reducing hemorrhage during operations. Once bleeding occurs, to stop the bleeding accurately and promptly by pressing, clamping, and suturing, and internal iliac artery ligation may be needed occasionally. Special attention should be paid to the hemostasis of the venous plexus of pelvic floor. PMID- 11783136 TI - [Treatment of childhood genital malignancies]. AB - OBJECTIVE: To present the clinical profile and the result of treatment in childhood genital malignancies. METHODS: Twenty seven childhood patients (< 12 years) with genital malignancies diagnosed and treated in Peking Union Medical College hospital were analyzed retrospectively focusing on the clinical characteristics and outcome of the treatment. RESULTS: Patients ranged in age from 2 to 12 years with mean 6.5 years at diagnosis. Of the 27 patients, 23 had ovarian malignancies including 21 (77.8%) germ cell tumor. Four of the patients had extragonadal tumors with 2 endodermal sinus tumor of the vagina, and 2 embryonic rhabdomysarcoma. In ovarian malignancies, abdominal mass and abdominal pain were main clinical features accounting for 77.8% and 74.1% respectively. In vaginal malignancies, vaginal bleeding and polypoid tumor of the vagina were important clinical manifestations. 91.3% (21/23) of the patients underwent only unilateral salpingo-oophorectomy with preservation of contralateral ovary and the uterus. Childhood genital malignancies were very sensitive to the chemotherapy. Postoperative vincristine, actinomycine, cyclophosphamide (VAC) or cisplatine, vincristine, blyomycine (PVB) chemotherapy was individualized according to the tumor site, International Federation of Gynecology and obstetrics stage and histopathology. Survival rate in our series was 71.4% during the follow-up time (mean 47.4 months). CONCLUSIONS: Malignant germ cell tumor of the ovary is the most common tumor in the childhood genital malignancies. Principle of primary surgery is preservation of fertility and chemotherapy is also considered as a very important treatment modality. PMID- 11783137 TI - [Application of mRNA differential display technique in screening related gene of endometrial carcinoma]. AB - OBJECTIVE: To screen related gene of endometrial cancer by mRNA differential display (DD)-polymerase chain reaction (PCR). METHODS: Individual mRNA from normal and neoplastic endometrium obtained from the same patient were comparatively studied by DD methodology. The mRNAs were isolated from the tissues, reverse transcribed to cDNA, and then amplified by PCR. The PCR products were displayed on a polyacrylamid gel by silver staining, and the differentially expressed bands were retrieved and reamplified. Subsequently we selected four bands for sequencing and making further investigation. RESULTS: cDNA homology was analysed by searching through GenBank sequence databases and indicated that tumor fragment (T1.7) has no significant sequence homology with any sequence of known function. Acession number is AF315581. Further study showed that T1.7 expressed more abundantly in endometrial cancer than hyperplasia endometrium, but not expressed in normal endometrium. CONCLUSIONS: T1.7 is a new expressed sequence tag. It may be related gene fragment of endometrial cancer. PMID- 11783138 TI - [Reversion of HBV-related liver fibrosis and early cirrhosis by baicao rougan capsule]. AB - OBJECTIVE: To observe the therapeutic effect of herbal compound, Baicao Rougan Capsule on human liver fibrosis and early cirrhosis associated with chronic hepatitis B. METHODS: Forty-two patients with liver fibrosis and 10 cases early cirrhosis were treated with a herbal compound for six months. Two liver biopsies were performed before and after treatment, their serum samples were collected before, in the middle of and after the treatment, all samples were measured at the same time. RESULTS: Improvement of clinical symptoms and signs occurred in 75% to 91% of the patients, serum ALT lowered to normal level in 68%. The serum level of type IV collagen, laminin and hyaluronic acid were significantly reduced by the end of treatment (P < 0.05). Grading score was reduced from 7.79 +/- 6.15 to 5.36 +/- 3.95 after treatment (P < 0.05), while staging score was reduced from 7.39 +/- 5.55 to 5.26 +/- 4.36 (P < 0.05). CONCLUSION: Chinese herbal compound Baicao Rougan Capsule is effective in the treatment, and in the reversal of HBV related liver fibrosis and early cirrhosis. PMID- 11783139 TI - [Immunoregulation of Youguiyin, Sijunzitang, Taohong Siwutang in treating patients with deficiency of kidney, spleen and blood stasis syndrome]. AB - OBJECTIVE: To study the different immunoregulatory effects of Youguiyin, Sijunzitang, Taohong Siwutang to patients with deficiency of Kidney, Spleen and blood stasis Syndrome respectively. METHODS: The treated group, 40 patients in each with deficiency of Kidney, Spleen and blood stasis were treated with Youguiyin, Sijunzitang and Taohong Siwutang respectively. Three control groups (20 patients each) were established respectively. Peripheral venous level of complement C3, circulating immunocomplex (CIC), interleukin-2 (IL-2), interferon gamma (IFN-gamma), lymphocyte transformation rate (LTR), the activity of natural killer (NK) cell, and the phagocytic function of neutrophil were measured before and after treatment. RESULTS: Sijunzitang could reduce the level of CIC (P < 0.01), raise the activity of NK cell and LRT (P < 0.01) of the patients with deficiency of Spleen syndrome; the same did the Youguiyin to that of patients with deficiency of Kidney syndrome. Also, Sijunzitang could increase the level of IL-2 in blood and the phagocytic function of neutrophil (P < 0.05); the Taohong Siwutang could lower the level of CIC to patients with blood stasis syndrome (P < 0.01), increase the activity of NK cells (P < 0.05). CONCLUSION: Youguiyin, Sijunzitang could enhance the immunoregulatory function of the patients with deficiency of Spleen and Kidney, particularly the cellular immune functions, in which the Sijunzitang effect is more complete and significant, while Taohong Siwutang eliminated the effect of CIC in blood better. PMID- 11783140 TI - [Clinical study on relationship of blood stasis syndrome with plasma endothelin and nitric oxide changes in acute pancreatitis patients]. AB - OBJECTIVE: To study the relationship of blood stasis Syndrome with plasma endothelin (ET) and nitric oxide (NO) in acute pancreatitis patients. METHODS: A healthy control group and three groups of patients with three different Syndromes of TCM were established. Patients' ET and NO were determined by radioimmunoassay and reversed-phase high performance liquid chromatography respectively before and after treatment. The NO level was represented by the sum of NO2 and NO3. RESULTS: ET and ET/NO ratio were not changed significantly in patients with Liver-Spleen Qi Stagnant Syndrome, but increased significantly in patients with Liver-Spleen Damp-Heat Syndrome or with Spleen Stomach excessive Heat Syndrome (P < 0.05 or P < 0.01). CONCLUSION: ET and ET/NO ratio might be the important objective markers of the existence of blood stasis Syndrome in acute pancreatitis patients. PMID- 11783141 TI - [Study on relationship between two different syndromes and three soluble cytokine receptors in patients with rheumatoid arthritis]. AB - OBJECTIVE: To study the relationship between two different Syndromes (Cold-Damp Syndrome and Damp-Heat Syndrome) and three soluble cytokine receptors (sCKR, soluble interleukin-2 receptor, sIL-2R, soluble interleukin-6 receptor, sIL-6R, soluble tumor necrosis factor receptor 1, sTNFR1) in rheumatoid arthritis (RA). METHODS: The serum levels of three soluble receptors were measured by ELISA in patients with RA. RESULTS: The serum levels of 3 sCKR were significantly elevated in RA patients compared to healthy controls and obviously lowered after treatment (P < 0.01). The level of sIL-2R was significantly higher in Cold-Damp Syndrome than that in Damp-Heat Syndrome (P < 0.01), but serum sTNFR1 was significantly higher in Damp-Heat Syndrome than that in Cold-Damp Syndrome, there was no obvious difference between sIL-6R of two Syndromes. CONCLUSION: The high serum sIL-2R and low sTNFR1 might be a criterion of Cold-Damp Syndrome, but the high sTNFR1 and low sIL-2R might be a criterion of Damp-Heat Syndrome, these criteria reflected some states of different functions in immune system in patients with RA. PMID- 11783142 TI - [Effect of Baoyuan Qiangshen capsule no. II on tubular interstitial injury in chronic renal failure patients]. AB - OBJECTIVE: To investigate the protective effect and mechanism of Baoyuan Qiangshen Capsule No. II (BYQS) in treating chronic renal failure (CRF). METHODS: Sixty patients of CRF were divided into 2 groups randomly, the tested group treated with BYQS combined with Lotensin and the control group treated with essential amino acid combined with Lotensin. Changes of renal function and tubular marked proteins were observed. RESULTS: The markedly effective rate and total effective rate of the tested group were 63.3% and 93.3% respectively and those of the control group were 30.0% and 56.7% respectively, the effect of the tested group was markedly better than that of the control group (P < 0.01). In the tested group after treatment, BUN, SCr and CCr were improved significantly, urine retinol binding protein and beta 2-microglobulin and N-acetyl-beta-D glucosamindase decreased significantly (P < 0.01), while Tamm-Horfau protein increased significantly (P < 0.05). CONCLUSION: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF. PMID- 11783143 TI - [Clinical observation on therapeutical effect of prepared rhubarb in treating pregnancy induced hypertension]. AB - OBJECTIVE: To study the effect of prepared rhubarb in treating patients with pregnancy induced hypertension (PIH) and its therapeutic mechanisms. METHODS: Prepared rhubarb and nifedipine were given to the study group, while the nifedipine was given to the control group alone. The blood lipid, renal function, blood coagulation, fibrinolysis and immunological parameters were monitored. RESULTS: In the study group, (1) Levels of triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) decreased and high density lipoprotein cholesterol (HDL-C) level increased significantly; (2) Plasma level of fibronectin (FN) and plasminogen activator inhibitor (PAI) lowered significantly, plasma antithrombin (AT-III) level unchanged; (3) Serum beta 2 microglobulin (beta 2-MG) level and urinary level of N-acetyl-beta-D-glucosaminidase (NAG) and interleukin-6 (IL-6) decreased significantly; (4) CD8 of blood increased, CD4/CD8 and circulating immune complex (CIC) of blood reduced obviously. All of the above mentioned parameters in the study group were significantly different from that of the control group. CONCLUSION: The prepared rhubarb could reduce the vascular endothelial cell's damage significantly and alter the immune balance, which is effective in treating the PIH. PMID- 11783144 TI - [Clinical and experimental study on Yinhua mixture aerosol in treating infantile viral pneumonia]. AB - OBJECTIVE: To explore the therapeutic effect of using Yinhua mixture aerosol in treating infantile viral pneumonia and its mechanism. METHODS: Comparing sixty nine infantile viral pneumonia patients using Yinhua mixture aerosol with 33 infantile viral pneumonia patients using gentamycin, pharmacodynamical animal experiments of anti-tussis and anti-asthma were also observed. RESULTS: The markedly effective rate of Yinhua mixture aerosol and gentamycin aerosol were 58.0% and 27.3% respectively, while the total effective rate of these two drugs was 95.7% and 69.7% respectively. Experimental study revealed that Yinhua mixture was effective in antifebrile, anti-asthma and expectorative effect, which was better than that of gentamycin (P < 0.05). CONCLUSION: Yinhua mixture aerosol is effective in antifebrile, anti-asthma, and expectorative effect. PMID- 11783145 TI - [Clinical and experimental study on effect of burn Jinhuang liquid in treating wound of II degree of burns]. AB - OBJECTIVE: To explore therapeutic effect of Chinese herbal drug Burn Jinhuang Liquid (BJHL) in treating II degree (II- and II+ degree) burn injury. METHODS: One hundred and twenty II degree burn patients were treated with BJHL, the clinical effect was compared with that of moist exposure burn ointment (MEBO). Animal experiments on the effect of BJHL were conducted. RESULTS: To compare with MEBO, BJHL has a better effect of bacteria inhibition and declining rate of wound infection and shortening time of wound healing through clinical and experimental study. There was no irritation to the burn wound, and it has no side and toxic effects to the liver and kidney. CONCLUSION: BJHL has a comprehensive effect of bacteria inhibition, analgesis and wound healing improvement. PMID- 11783146 TI - [Effect of replenishing liver and kidney, supplementing qi and activating blood circulation recipe on proliferation and relevant gene expression of vascular smooth muscle cells]. AB - OBJECTIVE: To study the effect of replenishing Liver and Kidney, supplementing Qi and activating blood circulation recipe (TCM) on the proliferation and relevant gene expression of vascular smooth muscle cells (VSMC). METHODS: Using 3H-TdR incorporation to investigate the VSMC proliferation, using Northern blotting and reverse Polymerase Chain Reaction (RT-PCR) to detect the effect of serum with TCM on induced NO synthase (iNOS), endothelin (ET) induced c-jun and proliferation cell nucleus antigen (PCNA) gene expression. RESULTS: The 3H-TdR incorporation value of VSMC treated by serum with TCM was lower than that of control serum (P < 0.05). Rich iNOS mRNA was detected in the VSMC stimulated by serum with TCM. Expressions of c-jun and PCNA gene induced by ET in the VSMC were significantly inhibited by serum with TCM. CONCLUSION: The TCM could significantly inhibit VSMC proliferation. PMID- 11783147 TI - [Effect of Yiqi Zishen granule on ultrastructure of glomeruli of IgA nephropathy in mice]. AB - OBJECTIVE: To study the effect and therapeutical mechanism of Yiqi Zishen granule (YQZSG) in treating IgA nephropathy. METHODS: One hundred and fifty mice were divided into 5 groups randomly, in every treatment group, the relevant drugs were given. Their kidney tissues were observed with light microscope and electron microscope in batches at the 3rd, 6th, 9th and 12th week. RESULTS: The glomerular mesangial cells and mesangial matrix were proliferative in the model group at the 6th, 9th and 12th week. The light density of glomeruli, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in the model group were obviously higher, the change of large and small dosage YQZSG group and positive Chinese drug group were similar, but milder in pathological degree. The light density of glomerulus area, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in large dosage YQZSG group were significantly lower than those in the model group (P < 0.05 or P < 0.01). CONCLUSION: YQZSG could inhibit the proliferation of mesangial cells and the mesangial matrix in IgA nephropathy. PMID- 11783148 TI - [Effect of acupuncture on enzymology of motor neuron of anterior horn of experimental spinal cord injury in rats]. AB - OBJECTIVE: To study the effect of acupuncture on enzymology of the motor neuron of anterior horn of injured spinal cord in rats. METHODS: Chemical staining method was used to quantitatively analyze the acetylcholinesterase (ACHE), succinate dehydrogenase (SDH), acid phosphatase (ACP), changes in motor neuron of anterior horn of spinal cord simultaneously, and auto-analysis photogram apparatus was used to quantitatively analyze. RESULTS: After spinal cord was injured, the AchE and SDH reduced, ACP raised; in the acupuncture group, ACHE and SDH were increased and ACP was lowered after acupuncture (P < 0.05, P < 0.01). CONCLUSION: Acupuncture could regulate enzymology of the motor neuron of anterior horn of injured spinal cord. Acupuncture could inhibit or delay the deterioration of neuron, and also could promote the recovery. PMID- 11783149 TI - [Integrated traditional Chinese and Western medical diagnosis and treatment of relapsed natural abortion]. PMID- 11783150 TI - [Advances in the study of reversal of multidrug resistance in neoplasm with Chinese herbal drugs]. PMID- 11783151 TI - [The raising of evidence-based medicine inspires the integration of traditional and Western medicine]. PMID- 11783152 TI - [Clinical observation of the treatment of infantile viral myocarditis with puerarin]. AB - OBJECTIVE: To observe the clinical effect of the treatment of infantile viral myocarditis with puerarin. METHODS: Puerarin was administered intravenously together with conventional treatment in the treated group, while that of conventional treatment solely was given in the control group. Creatine kinase isoenzyme, lactate dehydrogenase isoenzyme, cardiac function and clinical manifestations before and after treatment were observed. RESULTS: Puerarin could significantly relieve the symptoms of patients of infantile viral myocarditis, enhance the metabolism of myocardium and improve the cardiac function. The total effective rate of the treated group was 87.04%, significantly higher than that of the control group, the difference between them was significant (P < 0.05). CONCLUSION: Puerarin can be used to treat patients with infantile viral myocarditis with a satisfactory result. PMID- 11783153 TI - [Effect of puerarin on fibrinolytic activity and lipid peroxide in patients with coronary heart disease]. AB - OBJECTIVE: To observe the effect of puerarin on superoxide dismutase (SOD), lipid peroxidation (LPO), tissue plasminogen (TPA) and plasminogen activator inhibitor (PAI-1) of coronary heart disease (CHD) patients. METHODS: Forty-eight patients were divided into two groups (treated group and control group). Treated group was given intravenously 600 mg puerarin, once daily for one week, also the same treatment as that of control was given. Nitrite colorimetric method, radioimmunoassay (RIA), TBA fluorescent development process and fibrinolysin specific colorbase substrate decomposition development process were used to determine SOD activity, SOD, LPO, TPA and PAI-1. RESULTS: After the treatment with puerarin, SOD activity was increased, LPO reduced, while without any changes in the control group. There was insignificant changes of SOD between the treated and the control groups. TPA and PAI-1 were increased significantly in the treated group, but was insignificantly changed in the control group. CONCLUSION: Puerarin can increase the SOD activity, decrease LPO level and enhance the activity of fibrinolysis. PMID- 11783154 TI - [Effect of tongxinluo capsule in treating variant angina pectoris patients and its influence on endothelial function]. AB - OBJECTIVE: To assess the efficacy of Tongxinluo capsule (TXLC) in treating variant angina pectoris and its effect on endothelial function. METHODS: Sixty four patients with variant angina pectoris were enrolled in the study for four weeks by a randomized clinical trial treatment with TXLC or isosorbide mononitrate. RESULTS: (1) The symptoms of both groups were significantly improved, the total effective rate of TXLC and isosorbide were 86.67% and 87.10% respectively; (2) The level of serum nitric oxide was increased, and the serum endothelin was decreased after treatment, there was no significant difference between these two groups. CONCLUSION: TXLC could effectively improve the symptoms of variant angina pectoris, the mechanism of which may likely be mediated by nitric oxide and endothelin. PMID- 11783155 TI - [Effects of shenmai injection on plasma neuropeptide Y, endothelin and atrial natriuretic polypeptide in heart failure patients]. AB - OBJECTIVE: To investigate the effect of Shenmai injection (SMI) on neuroendocrine function in the patients with heart failure (HF). METHODS: Sixty patients with HF were randomly divided into the treated group administered with SMI combined with western medicine, and the control group administered with western medicine alone. The change of cardiac function was observed, and plasma neuropeptide Y (NPY), endothelin (ET) and atrial natriuretic polypeptide (ANP) were determined by immunoradiometric assay. RESULTS: The total effective rate and markedly effective rate were higher in the treated group than that of the control group, the level of NPY, ET and ANP of both groups were higher than healthy subjects. The plasma NPY, ET and ANP of both groups were significantly reduced after treatment, the effect of treated group was better than that of control group. CONCLUSION: SMI could improve the HF patient's cardiac function, reduce the level of plasma NPY, ET and ANP, their neuroendocrine activity was affected at the same time. PMID- 11783156 TI - [Clinical observation of the effect of shuxinsu capsule in treating angina pectoris]. AB - OBJECTIVE: To observe the therapeutic effect of Shuxinsu capsule (SXSC) in treating angina pectoris patients. METHODS: One hundred and fifty angina pectoris patients were divided into two groups. Group A (80 cases), randomly divided into two subgroups, SXSC treated and Yixin oral liquid (YXOL) control group, each group consisted of 40 cases. Group B (70 cases) was an openly treated group (OTG). RESULTS: 17 cases were markedly effective in the SXSC treated group in relieving the symptoms, effective were 16, the total effective rate was 82.50%, while in the control group, the markedly effective cases, the effective cases and the total effective rate were 13, 16 and 72.50% respectively; there was significant difference between these two groups (u = 1.99, P < 0.05). In the treated group (SXSC and OTG) of 110 cases, the markedly effective, effective cases on ECG were 34 and 30 respectively. The total effective rate was 58.18%, higher than that of the control group, which was 55.00%, but the difference was insignificant. The activity of SOD in RBC and the amount of plasma LPO were significantly different after treatment in the SXSC group. Both of the medications had effect to reduce serum total cholesterol (TC) and triglyceride (TG), the TC was lower and high density lipoprotein-cholesterol (HDL-C) higher significantly after treatment in the SXSC group. CONCLUSION: SXSC has significant effect on angina pectoris. PMID- 11783157 TI - [Histocytopathological study on gastric mucosa of spleen deficiency syndrome]. AB - OBJECTIVE: To explore the pictures of gastric mucosa of Spleen deficiency syndrome, and the relationship between the degree of pathological changes of gastric mucosa and types of Spleen deficiency syndrome. METHODS: One hundred and eighty-eight Spleen deficiency patients with organic diseases of heart, lung, liver, gallbladder, pancreas, intestine and kidney excluded were examined their gastric mucosa. Tests of histopathology and subcellular ultrastructure were conducted by using optical microscope, electron scanning microscope, electron transmission microscope and histochemical staining methods. RESULTS: The gastric mucosa of Spleen Qi deficiency and Spleen Yang deficiency patients could either be affected with organic lesion (type G) or unaffected (type F); the gastric mucosa of Spleen Yin deficiency and Spleen deficiency with Qi stagnation were both affected by gastric lesions, and the degree of their lesions was more serious than that of Spleen Qi deficiency of type G and Spleen Yang deficiency of type G, P < 0.05-0.01. CONCLUSION: Pathological changes did not necessarily occur in the gastric mucosa of Spleen deficiency patients; the degree of pathological changes was relevant with the evolution of Spleen deficiency types. PMID- 11783158 TI - [Clinical and experimental study on the treatment of myelodysplastic syndromes with fuzheng quxie tablet]. AB - OBJECTIVE: To study the mechanism of Fuzheng Quxie Tablet (FZQXT) in treating myelodysplastic syndromes (MDS). METHODS: Thirty-three cases of MDS were treated with FZQXT, changes of peripheral blood cells, morphology of bone marrow smear, bone marrow pathology and immunology were monitored before and after treatment. The effects of FZQXT on hematopoietic stem cells of mice were also observed. RESULTS: The remission rate and total effective rate were 24.24% and 72.72% respectively. FZQXT had obvious effect in promoting the proliferation of colony forming unit-erythrocytes (CFU-E). CONCLUSION: The beneficial effect of FZQXT in treating refractory anemia might be reached through promoting the proliferation of erythrocytic hematopoietic stem cells. PMID- 11783159 TI - [Cyclosporin A and erhuang sangshenzi decoction in treating 32 cases of severe aplastic anemia]. PMID- 11783160 TI - [Effects of garlicin tablet on plasma endothelin and nitric oxide in patients with coronary heart disease and angina pectoris]. PMID- 11783161 TI - [Effects of Astragaloside in treating myocardial injury and myocardial Sarco/Endoplasmic Ca(2+)-ATPase of viral myocarditis mice]. AB - OBJECTIVE: To investigate the effects on myocardial injury and sarcoplasmic reticulum (SR) Ca(2+)-ATPase of viral myocarditis mice treated with Astragaloside (AS) and Astragalus Injection (AI). METHODS: Viral myocarditis model was created by intraperitoneal inoculation with coxsackievirus B3m (CVB3m) solution and were divided into model, AS, AI and normal control groups. The mortality, myocardial pathological changes, serum cardiac troponin I (cTnI) and the activity of myocardial Sarco/Endoplasmic Ca(2+)-ATPase (SERCA) were observed. RESULTS: The mortality of model was higher than that of the normal control (P = 0.0042), AS and AI (P < 0.05). The serum level of cTnI of model was significantly higher than that of the normal control (P < 0.001), AS (P < 0.025) and AI (P < 0.05). The myocardial necrosis and inflammatory changes of AS and AI groups were alleviated than that of model (P < 0.01). The activity of myocardial SERCA of model were significantly lower than that of normal control (P < 0.001), AS (P < 0.01) and AI (P < 0.05). CONCLUSIONS: AS and AI have some protecting effects on myocardial injury of viral myocarditis mice. AS is the effective component of Astragalus membranaceus in treating viral myocarditis. One of the mechanisms of Astragalus membranaceus and AS for viral myocarditis mice depriving of the myocardial injury may be due to improve the activity of myocardial SERCA in the mice. PMID- 11783162 TI - [Experimental study of yishou tiaozhi tablet on free radical metabolism in aging model mice]. AB - OBJECTIVE: To observe the effect of Yishou Tiaozhi tablet (YSTZT) on the metabolism of free radical in mice of aging model. METHODS: Using the aging model induced by hypodermic injection of 5% D-Galactose in mice for forty days. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum, activity of monoamine oxidase B (MAO B), Na(+)-K(+)-ATPase in brain were investigated after the treatment. RESULTS: In comparing to the aging model group, it showed that YSTZT could obviously inhibit the increase of level of MDA in serum and the activities of MAO-B in brain; and enhance the activities of SOD, GSH-Px in serum, and the activities of Na(+)-K(+) ATPase in brain. Furthermore, YSTZT could obviously elevate the tolerance to fatigue and hypoxia in mice. CONCLUSIONS: YSTZT can effectively improve the free radical metabolism of senile body, it is an ideal and effective medicine in preventing aging, which is also one of the experimental basis in proving the theory of "Spleen and Kidney deficiency complicated with stasis and phlegm cause aging". PMID- 11783163 TI - [Effect of dingxin recipe on arrhythmia and injury induced by ischemia and reperfusion in rabbits]. AB - OBJECTIVE: To investigate the protective effect of Dingxin Recipe (DXR) on arrhythmia and injury induced by ischemia and reperfusion. METHODS: Rabbits were randomly divided into four groups and administered orally with DXR of high dose, low dose, propanolol and distilled water. Two-step coronary artery ligature was used to form ischemia and reperfusion model. Superoxide dismutase (SOD), cyclic adenosine monophosphate (cAMP), norepinephrine (NE), dopamine (DA), 5 hydroxytryptamine (5-HT), myocyte ultrastructural injury and occurrence of arrhythmia were investigated. RESULTS: DXR could obviously antagonize arrhythmia induced by myocardial infarction or ischemia and reperfusion in rabbits. Compared with the control group, DXR of high and low doses could improve the changes in ST T. In rabbits treated with DXR, the levels of SOD were elevated while cAMP, NE, DA, 5-HT and the whole blood viscosity were lowered. CONCLUSIONS: DXR could obviously antagonize arrhythmia and injury induced by ischemia and reperfusion, DXR may clear oxygen free radical, regulate the second messenger, inhibit sympathetic nerve system, improve local circulation, protect mitochondria and prevent the activation of lysosome and safeguard the cardiac myocyte to be free from injury. PMID- 11783164 TI - [Experimental study on effect of guyubao in promoting the fracture healing in kidney deficiency rabbits]. AB - OBJECTIVE: To study the effect of Guyubao (GYB) in promoting the fracture healing of Kidney deficiency (KD) rabbits. METHODS: Fifty-seven rabbits were randomly divided into three groups: The blank group (A), the control group (B) and the experimental group (C). After the periosteum was peeled off, 0.73 cm middle section defects on both radius were removed. One week after operation, the experiment was begun: Group A was fed normally; group B fed normally plus 6 mg/(kg.d) prednisolone; group C fed with food mixed with GYB and 6 mg/(kg.d) prednisolone. The general state and body weight were observed. The rabbits were sacrificed at three and six weeks after the beginning of experiment. Both radius were observed with X-ray and histologic examination. RESULTS: In group A, no KD appeared, group B gradually developed KD, and mild KD appeared in group C but adjusted rapidly. The healing of radial defect in order were C, A, B from higher to lower degree. CONCLUSION: The results revealed that the GYB could correct the KD and promote fracture healing. PMID- 11783165 TI - [Molecular standard of chemical essence in Chinese traditional medicine]. PMID- 11783166 TI - [Treatment of post-operational restenosis of percutaneous transluminal coronary angioplasty with traditional Chinese medicine]. PMID- 11783167 TI - [Increasing aging population creating social and health problems in society]. PMID- 11783168 TI - [Traditional Chinese and Western integrated medicine will stride forward to the world in the 21st century]. PMID- 11783169 TI - [Clinical study on effect of xianlong capsule on senile vascular dementia]. AB - OBJECTIVE: To assess the efficacy of Xianlong Capsule (XLC) in treating the senile vascular dementia (VD). METHODS: Forty-six cases of VD were randomly divided into two groups. The XLC group (24 patients) were treated with XLC and the control group (22 patients) were treated with Hydergine. Mini-mental state examination (MMSE), Hamilton depression scale (HDS) marks and clinical symptoms were observed in different groups. RESULTS: XLC could markedly increase MMSE and HDS marks of VD patients. XLC had the effect of improving balance and gait ability of VD patients. CONCLUSION: XLC had certain effect on VD and its effect was better than that of Hydergine. PMID- 11783170 TI - [Clinical observation on effect of yiqi huoxue decoction in comprehensive treatment on advanced stage of esophageal cancer]. AB - OBJECTIVE: To observe the effect of Yiqi Huoxue (Replenishing Qi and activating blood circulation, YQHX) decoction in patients with advanced stage esophageal cancer treated with radiotherapy (RT) and intervention chemotherapy (ICT). METHODS: In comparing 31 patients who were treated with RT and ICT (Group A), and 31 patients treated with RT and ICT plus YQHX decoction (Group B). RESULTS: Immediate effective rate were 48.4% in Group A and 64.5% in Group B (P > 0.05). The function of bone marrow in Group B was obviously higher than that in Group A. The 1 year metastasis rate in Group A was higher than that in Group B, but the long-term survival rate of Group B was obviously higher than that in Group A (P < 0.05). CONCLUSION: YQHX decoction could reduce the inhibition of bone marrow caused by radiotherapy and intervention chemotherapy, lower the metastasis rate, prolong the long-term survival rate and improve the quality of life. PMID- 11783171 TI - [Study on early application of Chinese medicinal herbs after total gastrectomy]. AB - OBJECTIVE: To evaluate the effect of Chinese medicinal herbs on digestive function, nutritional status, immune function and complication rate in patients after total gastrectomy. METHODS: Thirty-nine patients of gastrectomy were divided into two groups and were intubated into small intestine for administering postoperatively. Twenty-one of them belonged to the treated group and were dripped with Chinese medicinal herbs intraluminally during the early postoperative stage, while 18 cases of the control group were dripped with 0.9% sodium chloride. RESULTS: The digestive function of the treated group recovered rapidly, and the nutritional status and immune function improved markedly as compared with those of the control group (P < 0.001-0.05). CONCLUSION: Early application of Chinese medicinal herbs after total gastrectomy could promote the digestive function to recover to normal, the nutritional status and immune function to improve. The occurrence of complication was reduced. PMID- 11783172 TI - [Clinical and experimental study on treatment of Helicobacter pylori infected gastritis by xialian yiyou capsule]. AB - OBJECTIVE: To observe the therapeutic effect of Xialian Yiyou Capsule (XLYYC) on helicobacter pylori (HP) infected gastritis to develop the serial Chinese classical recipe. METHODS: HP infected patients were divided into two groups, 136 patients in the XLYYC group treated with XLYYC and 90 patients in the control group treated with Lizhu Dele Capsule, for 4 weeks as one therapeutic course, the clinical therapeutic effect was observed, and corresponding animal experiments were done. RESULTS: Clinical effect of the XLYYC group was better than that of the control group in improving clinical symptoms, relieving inflammation of gastric mucosa and eliminating HP (P < 0.05, P < 0.01). Results of animal experiment showed that XLYYC was superior than the control significantly in anti inflammation, analgesia, stomach emptying and curing gastric ulcer model (P < 0.05, P < 0.01). Without any adverse reaction has been found in acute toxicologic study. CONCLUSION: The therapeutic effect of XLYYC in treating HP infected gastritis was definite and safe, non-toxic. PMID- 11783173 TI - [Experimental study on the effect of yiyuan shengxue capsule on gamma-interferon and tumor necrosis factor-alpha in patients with chronic aplastic anemia]. AB - OBJECTIVE: To explore the effect of Yiyuan Shengxue capsule (YYSXC) on peripheral gamma-interferon (gamma-IFN) and tumor necrosis factor-alpha (TNF-alpha) in patients with chronic aplastic anemia (CAA). METHODS: Applying the assay of microcell lesion inhibitory and L595 cytotoxicity test to detect gamma-IFN and TNF-alpha level 36 thirty-six cases with CAA before and after treatment with YYSXC. RESULTS: To compare the test group with the normal group, the difference was significant before treatment (P < 0.05, P < 0.01), but after treatment, the difference was insignificant between these two groups (P < 0.05). To compare the group of Kidney Yin Deficiency with Kidney Yang Deficiency, both the difference of before and after treatment were significant. For the therapeutic effective rate, the group of Kidney Yang Deficiency was higher than that of Kidney Yin Deficiency. CONCLUSION: YYSXC could treat CAA through reducing the level of peripheral gamma-IFN and TNF-alpha of CAA patients, and the effect was through regulating the dysfunctional immune state. PMID- 11783174 TI - [Effects of ligustrazine on plasma platelet aggregation rate, thromboxane B2, 6 keto-prostaglandin F1 alpha and von Willebrand's factor in patients with acute onset of cor pulmonale]. AB - OBJECTIVE: To study the effect on large dose of Ligustrazine on the function of platelet and endothelial cells of patients with acute onset of cor pulmonale. METHODS: Platelet aggregation rate (PAR), thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), von Willebrand's factor (vWF), PaO2 and PaCO2 were assayed in 30 patients with acute onset of cor pulmonale and 26 cases of control before and after treatment of large dose of Ligustrazine. RESULTS: PAR, vWF, TXB2, TXB2/6-keto-PGF1 alpha and PaCO2 decreased (P < 0.05, P < 0.01), and 6-keto-PGF1 alpha, PaO2, SaO2 increased (P < 0.01) after treatment of Ligustrazine, and only PaCO2 decreased in control. CONCLUSION: Ligustrazine had the function of antiplatelet and protecting the endothelial cells. Large dose (800 mg/d) had no side-effects. PMID- 11783175 TI - [Clinical study on the interventional treatment of non-traumatic femoral head mecrosis by integrated traditional Chinese and Western medicine]. PMID- 11783176 TI - [Efficacy of Chinese recipes of replenishing kidney and activating blood circulation in female rats with osteoporosis induced by ovariectomy]. AB - OBJECTIVE: To investigate the efficacy of Chinese recipe of replenishing Kidney and activating blood circulation (RKABC) in female rats with osteoporosis induced by ovariectomy. METHODS: Fifty female SD rats at 12 months of age were chosen, and were divided into 5 groups; control, model, model plus nylestriol, RKABC (high dose) and RKABC (low dose). The model of osteoporosis was established by ovariectomy in rats for 12 weeks, and then was given different kinds of liquid and administered approximately for 12 weeks. General bone mineral density (GBMD), femur bending strength (FBS), serum-BGP and urine-Hyp/Cr were measured. RESULTS: GMBD, FBS in 3 treatment groups were significantly higher than those in the model group (P < 0.05), but lower than those in the normal control group (P < 0.05); GBMD, FBS in 2 RKABC groups were slightly higher than those in nylestriol's group (P > 0.05). Compared with model group, levels of serum BGP in 2 RKABC groups increased (P < 0.05) and in RKABC (H) treatment group increased almost the same as those in the control group (P > 0.05). In comparison with model group, levels of U-Hyp/Cr in 3 treatment groups decreased (P < 0.05, P < 0.01) but 2 RKABC treatment groups still significantly higher than those in the normal control group (P < 0.05). CONCLUSION: It indicated that RKABC could control osteoporosis in female rats induced by ovariectomy and seems to promote bone formation. PMID- 11783177 TI - [Comparative study of the regulation of kidney tonic and promoting blood circulation recipe on apoptosis in T cells of old rats]. AB - OBJECTIVE: To investigate the mechanism responsible for the observed reduction in T cell function of the Kidney Deficiency Syndrome. METHODS: After 18th activation with anti-CD3 mAb, the qualitative and quantitative analysis of apoptoses in T cells were performed by using DNA gel electrophoresis, TdT-mediated dUTP nick end labelling (TUNEL) and flow cytometry. RESULTS: The percentage of apoptotic cells was 47.0% in the old and 22.2% in the young group (P < 0.01). In the Kidney tonic group, the mean percentage of apoptotic cells was 31.2%, significantly lower than that in the aged group (P < 0.05). The mean percentage of apoptotic cells in the promoting blood circulation group was 43.3% and no significant difference was seen in the percentages of apoptotoic T cells from the promoting blood circulation group compared with the old group. CONCLUSION: Activation-induced excessive apoptosis of T cells is one of the mechanisms elucidating decreased T cell function of the Kidney Deficiency Syndrome and aging, the retardation of immune senescence by Kidney tonic recipe could be accounted for by down regulation of activation-induced apoptosis in T cells. PMID- 11783178 TI - [Effect of compound Chinese drug bailong on the expression of tumor suppressor genes and relationship with prekallikrein activator signal pathway in human gastric carcinoma BGC82-3 cell line]. AB - OBJECTIVE: To study the effect of compound Chinese drug Bailong on the transcription of Cyclin Dependent Kinase Inhibitor (CKI) p16INK4a, p21 and Rb, c myc genes, and the relationship between gene expression and cAMP-PKA pathway. METHODS: Using the traditional molecular biology methods (cell synchronization, molecular hybridization--Western blotting, Northern blotting, etc.) examine the gene expression. RESULTS: Bailong promoted the expression (both mRNA and protein) of p16INK4a obviously in G1 phase cells. When prekallikrein (PKA) inhibitor was added in the cells which were treated by Bailong, the mRNA and protein level of p16INK4a decreased. It was shown that the inhibited proliferation of BGC82-3 cell by Bailong may come from the enhanced p16INK4a gene expression in G1 phase. Being same as p16INK4a, tumor suppressor genes Rb, p21 and oncogene c-myc expression were all affected by Bailong. When PKA inhibitor was added, the results were reversed. CONCLUSION: Bailong can affect many anticancer genes (including p16INK4a, p21 and Rb genes) and oncogenes (including c-myc) transcription by regulating cAMP-PKA pathway. PMID- 11783179 TI - [Effect of caoguo zhimu decoction on N-methyl-D-aspartate receptor gene expression of epileptic kindling model in rats]. AB - OBJECTIVE: To explore the effect of Caoguo Zhimu decoction (CGZMD) on N-methyl-D aspartate (NMDA) receptor gene expression of epileptic model on rat brain. METHODS: Adopting the pentylenetetrazol (PTZ) kindling model to observe the NMDAR1 mRNA gene expression by situs hybridization. RESULTS: After 28 days of CGZMD treatment, the NMDAR1 mRNA gene expression on CA1, CA2, CA3 part of rat hippocampus reduced obviously, the comparison between experimental group and the model control group showed significant difference (P < 0.05). CONCLUSION: CGZMD decreased NMDAR1 mRNA gene expression, it may be caused the NMDA receptor decline, hence revealed its anti-epileptic effect. PMID- 11783180 TI - [Progress on the treatment of tumor with biological therapy medicated by Chinese herbal medicine]. PMID- 11783181 TI - [Clinical study on jinmaitong composita on diabetic peripheral neuropathy]. AB - OBJECTIVE: To verify the effect of Jinmaitong composita (JMTC) on red blood cell aldolase reductase activity (RBC-AR), RBC sorbitol (RBC-S) and nerve conductive velocity in diabetic peripheral neuropathy (DN). METHODS: Sixty-six patients with DN were divided randomly into two groups, 33 patients in treated group treated with JMTC and 33 cases in the control group treated with Jinkui Shenqi (JKSQ), RBC-AR, RBC-S and nerve transmission speed were observed before and after three months treatment. RESULTS: Level of RBC-AR, RBC-S apparently decreased and nerve conductive velocity increased (P < 0.05, P < 0.01) after TMTC treatment. CONCLUSION: JMTC was able to improve the nerve conduction significantly with a lowering of RBC-AR and RBC-S and has good result in treating Diabetic peripheral neurophathy. PMID- 11783182 TI - [Staging-syndrome differentiation in treating diabetic foot disorder and its effect on hemodynamic changes of lower extremities with arterial ultrasonic Doppler diagnostic apparatus]. AB - OBJECTIVE: To observe the therapeutic effect of staging-Syndrome Differentiation of TCM in treating the diabetic foot disorder and the corresponding hemodynamic changes in lower extremities. METHODS: Chromatic ultrasonic Doppler diagnostic apparatus (ATL-ULTRAMARK 9 HDI, made in USA) was used to determine the arterial hemodynamic changes and clinical effect on the treatment of diabetic foot disorder in 60 non-insulin dependent diabetes mellitus (NIDDM) patients, among them 30 were treated by staging-Syndrome Differentiation of TCM, and the other 30 as control group treated with 654-2, and the 30 cases of nondiabetic foot disorder as normal control group in comparison. RESULTS: Compared to the normal control, the intravascular diameter, blood flow of both treated groups reduced, maximal and minimal speed of blood flow, and the mean speed were accelerated. Values in dorsal pedis artery had present the most sensitive one. In the comparison between before and after treatment, both treated groups were hemodynamic improvement in the lower extremities' artery, more obviously the dorsal pedis artery, while the comparison between these two groups showed that TCM staging-Syndrome Differentiation had a superior effect on lower extremities' hemodynamics to that of 654-2 group. The comprehensive assessment revealed that the treated groups was also significant different in comparing to that of normal control group (P < 0.05). CONCLUSION: The comprehensive TCM treatment of staging Syndrome Differentiation as the main therapeutic component was prominently better than that of 654-2 application in the treatment. PMID- 11783183 TI - [Clinical study on tangshen mixture in treating diabetic nephropathy]. AB - OBJECTIVE: To investigate the effects of Tangshen Mixture (TSM) on the serum glucose, quantity of proteinuria per 24 h, hypercoagulative status and oxidative injury in patients with diabetic nephropathy (DN). METHODS: Ninety-three patients with DN were randomly divided into treated group and control group. 48 patients in the former were treated with insulin and TSM, while the latter was treated with insulin alone. Before and after treatment, the levels of fasting blood glucose (FBG), 2 h after meal blood glucose (PBG), 24 h urinary albumin (24 h pro), endothelin (ET), alpha-granule membrane glycoprotein-140 (GMP-140), erythrocyte superoxide dismutase (ESOD), lipid peroxidase (LPO) were measured. RESULTS: After two months treatment, compared with the control group the levels of ET and GMP-140, LPO, and 24 h-pro lowered obviously (P < 0.01, P < 0.05), and the level of ESOD increased (P < 0.05) in the treated group, no obvious change was found in control grout after treatment. CONCLUSION: TSM could improve the hypercoagulative status, alleviate the renal free radical disturbances, and reduce the urinary protein loss. PMID- 11783184 TI - [Significance of platelet CD62p, CD63 assessment in type 2 diabetes mellitus patients with blood stasis]. AB - OBJECTIVE: To study the relationship between blood stasis and platelet activation and the influential factors on the latter in type 2 diabetes mellitus (DM) patients. METHODS: Platelet CD62p, CD63 expressions were determined in 30 patients of type 2 DM with blood stasis, 27 patients of type 2 DM without blood stasis and 20 normal controls by flow cytometry. RESULTS: CD62p, CD63 levels were significantly higher in type 2 DM with blood stasis group than that without blood stasis group and in normal controls. CD62p was positively correlated with CD63, while positive correlation existed between HbA1c, LDL-C and CD62p in DM patients with blood stasis. CONCLUSION: The increased level of platelet activation was the primary molecular basis in type 2 DM. It was important to perform the Syndrome Differentiation of blood stasis and treatment of activating blood circulation to remove blood stasis in type 2 DM. PMID- 11783185 TI - [Effect of running granule on repairing capacity of neuro-endocrine-immunity and DNA in treating mastoplasia]. AB - OBJECTIVE: To explore the clinical effect and therapeutic mechanism of Runing Granule (RNG) in treating mastoplasia to elucidate its pathogenesis. METHODS: One hundred and eighty-seven patients suffering from mastoplasia were randomly divided into the RNG treated group (treated group, 147 cases), and the tabellae tamoxifen control group (control group, 40 cases). The follow-up underwent for 3 months. Before and after treatment, changes of levels of plasma neurotransmitters, serum endocrine hormone, peripheral lymphocyte unscheduled DNA synthesis, the count of T lymphocyte subsets in the luteal phase during the menstrual cycle of 104 cases were measured, their clinical effects were also observed. RESULTS: Before treatment, these cases showed disturbances in the secretion of 5-hydroxytryptamine (5-HT), epinephrine (E), estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), and the levels of norepinephrine (NE), prolactin (PRL), inducer-helper T lymphocytes (OKT4+), suppressor T lymphocytes (OKT3+), were significantly increased, progesterone (P), testosterone (T), total T cells (OKT3+), OKT4+/OKT8+ ratio, unscheduled DNA synthesis (UDS) were obviously reduced (P < 0.05, P < 0.01) in mastoplasia patients. After treatment, RNG showed regulation on disturbances of these parameters, the curative rate of the treated group was higher than that of the control group; the metabolic disturbances of 5-HT/NE, E2/P, T, OKT3+ in the treated group were improved more significantly than those in the control group (P < 0.05). During the period of clinical observation, no obvious side effect and toxicity of RNG were found. CONCLUSIONS: Mastoplasia is caused by the interactions among multi-factors in which the neuro-endocrine-immune network plays a key role in the pathogenesis of mastoplasia. RGN was effective in treating mastoplasia, the mechanism probably lays on the regulation of comprehensive coordination from the multi-layers, multi-links and multiple pathways in the neuro-endocrine-immunity network and elevation of internal environment-stabilizing capacity of the body. PMID- 11783186 TI - [Clinical observation on treatment of endometriosis by tonifying qi and promoting blood circulation to remove stasis and purgation principle]. AB - OBJECTIVE: To explore the therapeutic mechanism of endometriosis by the treatment of Yiqi Huoxue Huayu Tongfu Principle (YQHXHYTFP, tonifying Qi and promoting blood circulation to remove stasis and purgation therapy) with Neiyi 1+ pill. METHODS: Forty-five cases with endometriosis were divided randomly into TCM group (30 cases, treated with Neiyi 1+ pill) and the control group (15 cases, treated with tamoxifen). The activity of natural killer cell of peripheral blood, T lymphocyte subsets, secreting interleukin-II and the EmAb were determined. RESULTS: Endometriosis is associated with immunologic disturbance. After treatment, the activity of NK cells and the count of T-suppressor cells were significantly increased (P < 0.01), the count of T-helper cells, the secretion of interleukin-II and TH/TS ratio were significantly reduced (P < 0.01). Over 50% of the cases whose EmAb was positive eventually turned to negative. The effective rate of this therapy was 90%. There was no significant difference between TCM group and the control group. CONCLUSION: YQHXHYTF therapy could modulate the immunologic disturbance in women with endometriosis, improve the clinical symptoms and signs obviously. It is a safe and effective therapy. PMID- 11783187 TI - [Clinical and experimental research on chronic atropic gastritis treated by weiyan mixture]. PMID- 11783188 TI - [Effect of tripterine on concentration of free calcium and hydrogen in vascular smooth muscle cells]. AB - OBJECTIVE: To investigate the effects of tripterine on concentration of free calcium (Ca2+) and hydrogen (H+) in vascular smooth muscle cells (VSMC). METHODS: By using fluorescence staining method, changes of the free calcium and hydrogen in single VSMC were studied with laser confocal scanning analyzer after different concentrations of fetal calf serum (FCS), tripterine and FCS plus tripterine were added into the culture pools respectively. RESULTS: The concentration of intracellular Ca2+ increased rapidly, sequentially and significantly after addition of 30% FCS (P < 0.05), 0.3 mg/L tripterine plus 30% FCS had inhibition effect on the concentration of the intracellular Ca2+, 20% FCS reduced the concentration of intracellular H+ significantly (P < 0.05), and 0.2 mg/L tripterine caused a significant increasing concentration of H+ (P < 0.05). CONCLUSION: Tripterine has an antagonistic action on the increasing concentration of intracellular Ca2+ induced by FCS, the inhibitory effect of tripterine on the Ca2+ channel of VSMC membrane may be responsible for this new mechanism. PMID- 11783189 TI - [Effect of alum on intestinal microecological balance in mice]. AB - OBJECTIVE: To observe the degree of microecological imbalance induced by alum in normal intestine of mice, and the bacterial adherence activity in the intestine of the mice administered orally with alum. METHODS: The mice were medicated orally with alum of small and large doses (0.25 g/kg and 1 g/kg) for 8 weeks, then 5 weeks after stopping administration of alum, microflora analysis and bacterial adherence to intestinal mucosal epithelial cells were carried out respectively. RESULTS: Eight weeks after administration with alum, the counts of Bifidobacteria and Lactobacilli decreased significantly, but the numbers of pathogenetic E. Coli increased significantly. The adherence rate of Bifidobacteria to the enterocytes of mice reduced markedly, but E. Coli was on the contrary of Bifidobacteria. Five weeks after the ceasing of medication, the intestinal flora were balanced, the adherence rate of both strains as mentioned above recovered to normal level. CONCLUSION: The imbalance of intestinal flora of mice administered with alum for a long time were only the transient change of bacterial counts. The imbalance of intestinal flora and the adherence rate of bacteria regained normal status five weeks after cancelling action factor. PMID- 11783190 TI - [Study on antitumor activity and mechanism of Ganoderma polysaccharides B]. AB - OBJECTIVE: To study the antitumor activity and mechanism of Ganoderma polysaccharides (GL-B). METHODS: Both in vivo and in vitro experiments were conducted in the study. Proliferation of tumor cells was detected by MTT method, tumor necrosis factor alpha (TNF alpha) was detected by biological assay, and interferon gamma (IFN gamma) by enzyme-linked immunosorbent assay (ELISA). The level of mRNA was detected with the method of reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: (1) GL-B 50, 100, 200 micrograms/ml inhibited the growth of implanted sarcoma 180 in vivo significantly and dose-dependently. (2) GL-B directly adding to the cultured medium neither induced HL-60 apoptosis nor restrained its proliferation in vitro. (3) The macrophages and T lymphocytes cultured medium treated with GL-B significantly induced HL-60 apoptosis and inhibited its proliferation. GL-B significantly increased TNF alpha and IFN gamma release and their mRNA expression in the cultured medium. CONCLUSION: The anti tumor activity of GL-B was derived from promoting mRNA expression of TNF alpha and IFN gamma, resulting in TNF alpha and IFN gamma release. PMID- 11783191 TI - [Clinical epidemiological principle and method should be taken as an important measure in scientific research of traditional Chinese medicine]. PMID- 11783192 TI - [Treatment of acute hemorrhagic apoplexy with recipe of activating blood circulation to remove stasis]. PMID- 11783193 TI - [The teratogenic, mutagenic effects and injury of cyclophosphamide and protection of Chinese herbal medicine against them]. PMID- 11783194 TI - [Clinical and experimental study of jianruling in treating hyperplasia of mammary gland]. AB - OBJECTIVE: To observe the therapeutic effect of Jianruling (JRL) on hyperplasia of mammary gland (HMG) and to explore its mechanism in regulating sex hormones. METHODS: Clinical changes of HMG were observed and serum sex hormones measured before and after JRL treatment. In experimental study, the effect of JRL was estimated by using electron microscope, pathologic and radioimmunoassay. RESULTS: JRL could not only cure HMG, but also regulate the sex hormone secretion both in HMG patients and in rats. Clinical study showed that the clinical cure rate was 72.5%, and the total effective rate was 90.8%, it demonstrated a significant difference in comparing with the control group, P < 0.01. The estradiol and prolactin levels of patients lowered significantly after JRL treatment, P < 0.05, while progestogen and testosterone increased significantly, P < 0.05, but no significantly change of follicle-stimulating hormone and luteinizing hormone was found. JRL showed marked effect in treating and preventing experimental HMG in rats, it could modulate the secretive function of sex hormone, and improve the construction of mammary gland. CONCLUSION: JRL has significant effect in treating HMG, it can adjust the endogenous sex hormone level, delay the development of chronic cystic hyperplasia of mammary gland. PMID- 11783195 TI - [Observation on effect of integrated Chinese and Western medicine in treating patients with peripheral atherosclerosis obliterans]. AB - OBJECTIVE: To observe the therapeutic effect of integrated traditional Chinese and western medicine (TCM-WM) and its influence on plasma endothelin-1 (ET-1), nitric oxide (NO) and apoproteins. METHODS: Ninety patients of peripheral atherosclerosis obliterans (ASO) were divided into three groups randomly and treated with Salvia injection (SI), prostaglandin E1(PGE1) and SI + PGE1 respectively. The clinical manifestation of patients was observed dynamically, plasma level of ET-1, NO and apoprotein were tested before and after treatment by radioimmunoassay, Griss method, immuno-transmission method and enzyme method. RESULTS: The cure rate of the SI, PGE1 and TCM-WM group was 26.67%, 33.33% and 46.67% respectively, the effective rate of them was 26.67%, 40.00% and 43.33% respectively. The therapeutic effect of the TCM-WM group was better than that of the SI and PGE1 group, P < 0.01. The plasma level of ET-1, NO and apoprotein was positively correlated with the stage altering of ASO, it was normalized gradually when ASO was alleviating effectively. CONCLUSION: The TCM-WM therapy has good clinical effect in treating ASO. To observe the change of ET-1, NO and apoprotein level before and after treatment dynamically is helpful to judge the severity, progress of disease and effect of treatment, and has high clinical significance. PMID- 11783196 TI - [Preliminary study on Chinese herb induced apoptosis of thyrocytes in Graves' disease]. AB - OBJECTIVE: To investigate the cellular and molecular mechanisms of some Chinese herbs on apoptosis of thyrocytes in Graves' disease. METHODS: Thirteen patients of Graves' disease were treated by anti-thyroid drugs and Chinese herbs were added in the therapeutic period for 2-10 weeks. Thyroid tissue of patient was sucked by percutaneous aspiration before and after adding Chinese herbs for observing the cellular morphology by fast red tablet staining, monitoring the cell apoptotic ratio by flow cytometry and terminal uridine deoxynucleotidyl end labelling (TUNEL) method to observe the effect of anti-thyroid drugs combined with Chinese herbs on Graves' disease. RESULTS: Compared with that treated with anti-thyroid drugs alone, after the combined therapy, the size of thyroid decreased significantly, P < 0.01. Typical apoptosis appearance, such as vacuolated cell, marginal nuclei, chromatin condensation and nuclear fragmentation, could be seen under light microscopy. The apoptotic rate before and after adding Chinese herbs was (2.11 +/- 1.78)% and (18.66 +/- 20.01)% respectively (P < 0.01). TUNEL positive cells were detectable for up to 2-20 weeks after Chinese herbal treatment. CONCLUSION: Some Chinese herbs could induce cell apoptosis when used in combination with antithyroid drugs in treating Graves' disease. PMID- 11783197 TI - [Influence of pre-operational medicated dachengqi granule on inflammatory mediator in tumor patients]. AB - OBJECTIVE: To find a simple, effective, with few side effect method of pre cleaning intestine for surgical operation of abdominal malignancy. METHODS: Thirty-five patients of abdominal malignant tumor were divided into two groups randomly and treated with Dachengqi Granule (DCQG) and routine western management (including oral taking antibiotics and enema with soap solution) respectively. Serum level of nitric oxide (NO), tumor necrosis factor (TNF), intercellular adhesive molecule-1 (ICAM-1), and enteric function recovering of patients were observed before operation, and 1, 3 and 7 days after operation. RESULTS: Time of borborygmus recovering and gas discharging after operation in the DCQG group was earlier than that of the control group, P < 0.05. Serum NO level was raised in both groups after operation, and reaching peak level at 3rd day post operationally, as compared with pre-operation, P < 0.05, the difference between the two groups was insignificant. Serum TNF level lowered in both groups, but more apparent in the DCQG group, the inter-group difference was significant at the first day of operation, P < 0.05. Serum ICAM-1 level in the DCQG group decreased at the day 3 after operation with significant difference in comparison with pre-operational level, P < 0.05, but in the control group, change of ICAM-1 before and after operation was insignificant. The mean ICAM-1 level of the DCQG group at the day 3 post-operationally was significantly lower than that of the control group, P < 0.05. CONCLUSIONS: Compared with the routine management of western medicine, using DCQG for intestine pre-cleaning before operation could obviously lower the operation induced inflammatory reaction of tumor patients, reduce the secretion of inflammatory mediator, improve the recovery of enteric function and reduce the post-operational complication. Therefore, applying DCQG for pre-operational enteric preparing could provide a satisfactory effect in surgical operation of abdominal malignancy. PMID- 11783198 TI - [Discussion and preliminary application on standard for comprehensive efficacy assessment of traditional Chinese medicine in treating malignant tumor]. AB - OBJECTIVE: To establish a comprehensive efficacy assessment standard on premise of patients' survival period and referring to the response of tumor and host to traditional Chinese medicine (TCM) therapy. METHODS: A standard was established by taking change of tumor size, tumor related symptoms, Karnofsky scoring and body weight of patient as criteria for evaluation. The standard was used to evaluate the comprehensive effect on advanced tumor patients, received various therapeutic regimen of TCM treatment in Xiyuan Hospital from March 1997 to August 1998, and compared with that evaluated by objective response rate (RR) of tumor. RESULTS: By the new standard, comprehensive therapeutic effect of 55 advanced tumor patients was: effective in 17 cases (30.91%), stable in 10 (18.18%) and exacerbative in 28 (50.91%), while by RR, it was completely response in 0, partial response in 3 (5.45%), no change in 41 (74.55%) and progressive disease in 11 (20.00%). Results of evaluation made by the two standard was different significantly, P < 0.005. The median survival period of 18 cases of advanced lung carcinoma patients was 11.5 months. Patients survived longer than the median survival period, mostly were tumor-bearing survival, were attributed to no change by RR, but were listed as effective by the new standard. CONCLUSION: The new standard laid more stress on quality of life than the RR, it reflects better response of tumor and host to treatment, and the prognosis of patients, and associated with the survival period, therefore, it could be conducted as the standard for comprehensive efficacy assessment in treating advanced malignant tumor in clinical practice after further improving. PMID- 11783199 TI - [Clinical observation on effect of step respiration exercise combined Chinese drug therapy in treating pulmonary heart disease and exploration on its therapeutic mechanism]. AB - OBJECTIVE: To introduce an auto-electrocardial counterpulsation device, which is non-invasive, nonmedicative and easy to operate, to patients of pulmonary heart disease. And to observe the therapeutic effect of the step respiration exercise (SRE) induced by the device combined with Chinese drug therapy (CDT) on pulmonary heart disease. METHODS: Fifty cases of chronic pulmonary heart disease were divided into SRE group, CDT group and CDT combined SRE group. Blood gas analysis and color ultrasonic Doppler cardiovascular function test were carried out in patients before and after treatment. RESULTS: After 3 courses of treatment, the effect of CDT combined SRE group revealed better than that of the other two groups. CONCLUSIONS: Respiration activity has definite influence on cardiovascular function of patients. SRE can significantly lower the heart rate, reduce the afterload, increase the pressure on coronary orifice by raising arterial diastolic pressure, enhance stroke output and alleviate the work of the heart. CDT can enhance the effect of SRE by synergetically removing pathogens to liberate the Lung, arresting the reversed Qi flow to remove Phlegm and relieve asthma, and replenishing the Kidney to control the reversed Qi. PMID- 11783200 TI - [Effect of tiangui recipe on serum leptin and pituitary gonadotropin in androgen sterilized rats]. AB - OBJECTIVE: To explore the effect of Tiangui Recipe (TGR) on obesity and reproductive function in androgen-sterilized rats (ASR). METHODS: ASR model was established by subcutaneous injection of testosterone propionate to SD female rats of 9 days age. Change of serum leptin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in model rats of 115 days old before and after feeding TGR was measured by radioimmunoassay (RIA). Meanwhile, criteria of energy state, including diurnal food intake, retroperitoneal fat depot weight and body weight, were measured and evaluated. RESULTS: ASR had the characteristics of high metabolic rate, energy imbalance and obesity. Serum level of leptin increased and FSH, LH decreased significantly (P < 0.01) in model rats as compared with the normal rats. Significant positive correlation between leptin level and body weight (r = 0.8977, P < 0.001) was observed, and negative correlation was seen between FSH, LH and leptin (r = -0.7517, P < 0.001; r = -0.8444, P < 0.001, respectively). The endocrinous changes of ASR all returned to normal range after the TGR treatment. CONCLUSION: Obesity and concerned hypogonadotropic hypogonadal anovulation were expressed in ASR. TGR may play an important role in reducing weight and inducing ovulation. PMID- 11783201 TI - [Apoptosis inducing effect of meisoindigo on K562 cells]. AB - OBJECTIVE: To study the effect of meisoindigo on human chronic myelogenous leukemia (CML) cell line K562 cells for exploring the mechanism of meisoindigo in treatment of CML. METHODS: Multiple methods, including dose-response curve, trypan blue exclusion, cytomorphology, DNA electrophoresis, flow cytometry and TUNEL (TdT mediated dUTP nick and labeling), were used to observe the effect of meisoindigo on K562 cells. RESULTS: Meisoindigo can inhibit the proliferation and induce the apoptosis of K562 cells. CONCLUSION: The therapeutic mechanism of meisoindigo in treating CML may be related with its proliferation inhibiting and apoptosis inducing effect in CML cells. PMID- 11783202 TI - [Influence of flavonoid of Astragalus membranaceus's stem and leaves on the function of cell mediated immunity in mice]. AB - OBJECTIVE: To investigate the immune regulation of flavonoid of Astragalus membranaceus's stem and leaves (FAM). METHODS: Changes of total T cell count and subsets in mice were determined by monoclonal antibody assay before and after treatment with FAM, and the LAK activity was tested simultaneously by isotope technique. RESULTS: FAM could promote the proliferation of lymphocytes induced by ConA, raise the T cell count and regulate the T cell subsets disorder, elevate the LAK activity induced by IL-2. CONCLUSION: FAM possesses the effect of immune stimulation and immune regulation in treating immunosuppressive mice. This study provides the experimental basis for clinical application of FAM. PMID- 11783203 TI - [Experimental study on multi-infarct dementia treated with reinforcing essence to refresh mental activity method]. AB - OBJECTIVE: To explore the mechanism of multi-infarct dementia (MID) treated with reinforcing essence to refresh mental activity method (RERM). METHODS: MID rat models were established by injecting sterile dry blood clots into common carotid artery and screening by the first jumping-off latency of diving platform reflex. Effect of RERM on model rats in learning, memory, serum and brain malondialdehyde (MDA), superoxide dismutase (SOD) level, brain monoamine neurotransmitter content, and brain morphosis were observed. RESULTS: Obvious malfunction of learning and memory was found in MID rat models, and there were also significant decreasing of monoamine neurotransmitters content in partial brain zones, decreasing of SOD activity in brain and increasing of MDA content in serum and brain. RERM could obviously improve learning and memory, raise SOD activity and monoamine neurotransmitters content in brain tissue, lower MDA content in serum and brain of MID rat models, protect brain morphosis of multi-infarction rats. CONCLUSION: RERM might treat MID by restraining lipid peroxidation, improving monoamine neurotransmitters content in partial brain zones and decreasing ischemic damage of brain tissue. PMID- 11783204 TI - [Therapeutic study of gastric precancerous condition]. PMID- 11783205 TI - [Endothelin and study of Chinese traditional medicine]. PMID- 11783206 TI - [Current situation and prospect of researches on tumor cell differentiation induced by Chinese herbal medicine]. PMID- 11783207 TI - [Clinical study on treatment of rectal carcinoma with Chinese herbal medicine and high dose fluorouracil emulsion via rectal infusion]. AB - OBJECTIVE: To study the clinical significance of rectal infusion of Chinese herbal medicine (CHM) plus high dose fluorouracil emulsion in treating rectal carcinoma. METHODS: The 86 patients of rectal carcinoma were randomly divided into CHM plus chemotherapy group and single chemotherapy group, and the changes of T-lymphocyte cell subset, natural killer (NK) activity, pathologic picture and clinical symptoms were analysed statistically before and after treatment. RESULTS: In the single chemotherapy group, the CD3 cell and NK activity decreased after treatment and most of the peri-carcinoma cellular infiltration were in grade I. In the CHM plus chemotherapy group, the CD3, CD4/CD8 and NK activity restored and CD8 lymphocyte decreased markedly after treatment in comparing with those before treatment (P < 0.05, P < 0.01), and most of the peri-carcinoma cellular infiltration concentrated in grade III. CONCLUSION: Chemotherapy alone could suppress cellular immune function significantly, significant immunoregulation and improvement of symptoms (as mucous-bloody stool, frequent defecation) could be obtained by combination therapy of CHM and chemotherapy. PMID- 11783209 TI - [Clinical and experimental study on treatment of retention enema for chronic non specific ulcerative colitis with quick-acting kuijie powder]. AB - OBJECTIVE: To study the clinical effect and mechanism of retention enema with quick-acting Kuijie powder (QAKJP) in treating chronic non-specific ulcerative colitis (CUC). METHODS: A treatment group of 156 patients treated with QAKJP and a control group of 78 patients treated with sulfasalazine orally were established randomly and their scores of main symptoms and signs were measured and compared before and after treatment. Animal experiments were conducted at the same time. RESULTS: The total effective rate in the treatment and the control group was 98.7% and 70.5% respectively, the clinical cure rate was 78.2% and 6.4% and the recurrence rate was 5.3% and 20.0% respectively. The effect of the treatment group was markedly superior to that of the control group, P < 0.01. Experimental study showed QAKJP could rapidly alleviate the congestion and edema of intestinal mucosa, promote the healing of ulcer, inhibit spasm of colon and had significant antidiarrheal action and antagonist effect against allergic mediator histamine. CONCLUSION: Retention enema with QAKJP has good effect on CUC, low recurrence rate and no toxic and side effect. PMID- 11783208 TI - [Clinical observation on radio- or chemotherapy plus Traditional Chinese medicine in treating brain metastatic tumor]. AB - OBJECTIVE: To observe the clinical efficacy of radio- or chemotherapy plus traditional Chinese medicine (TCM) by Syndrome Differentiation in treating brain metastatic tumor. METHODS: Forty-one patients were randomized into four groups: Group A treated with chemotherapy plus TCM, Group B with radiotherapy plus TCM, Group C with chemotherapy alone and Group D with radiotherapy alone. The efficacies of the four groups were compared. RESULTS: The short-term response rate, living quality, 1-, 2-, 3- and 4-year survival rate, median survival period and immunity of the Group A and B were significantly higher than those of the Group C and D (P < 0.05). CONCLUSION: Radio- or chemotherapy plus TCM by Syndrome Differentiation has the effect of tumor growth inhibition, survival period extension and living quality enhancement in treating brain metastases. PMID- 11783210 TI - [Clinical and experimental study on treatment of ankylosing spondylitis]. AB - OBJECTIVE: To explore the effect and mechanism of Gubiyin (GBY) in treating ankylosing spondylitis (AS). METHODS: The 70 patients of AS were randomly divided into two groups, 40 patients in the GBY group were treated with GBY and 30 patients treated with indomethacin for control. Animal experiments were also conducted. RESULTS: Clinical observation showed that the markedly effective rate of the GBY group (57.5%) was higher than that of the control group (23.3%, P < 0.01), but the total effective rate of the two groups were similar. The effects of GBY in relieving symptoms of joints, improving function of joints, preventing degeneration of bone and improving laboratory parameters were better than those of indomethacin. In animal experiments, GBY showed its inhibition on granuloma formation, adjuvant arthritis in mice, and IL-1 production of abdominal macrophage and IL-2 production of spleen cell in rats. CONCLUSION: GBY has effects of anti-inflammation, analgesic, immunoregulation, inflammation mediator inhibition and hemorrheology improvement. PMID- 11783211 TI - [Light puncture combined with longhu xingnao granules in treating acute traumatic intracranial hematoma]. AB - OBJECTIVE: To confirm the clinical therapeutic effectiveness of Longhu Xingnao Granule (LHXNG) medicated after light puncture in treating acute traumatic intracranial hematoma. METHODS: Patients were randomly divided into two groups, 30 patients of the tested group were treated with LHXNG after light puncture and 20 patients of the control group treated with western medicine alone. RESULTS: The effect of the tested group was evidently superior to the control group (P < 0.05) and with a markedly shortened resuscitation time (P < 0.05). CONCLUSION: LHXNG has the function of promoting blood circulation and arresting bleeding, and improving resuscitation. In coordination with light puncture, it could improve the living quality of patients, shorten the resuscitation and treatment time, so as to reduce the maim and death rate. PMID- 11783212 TI - [Effect of nourishing kidney to inducing resuscitation method on psychic evaluation table in patients of vascular dementia]. AB - OBJECTIVE: To probe the effect of the nourishing Kidney to inducing resuscitation (NKIR) on psychic evaluation table in patients of vascular dementia. METHODS: Modified Sanjiasan Granule (MSG), a representative recipe of NKIR, was used to treat 26 patients with vascular dementia, 7 g per day orally for one month as one therapeutic course, and the effect of treatment was evaluated by psychic evaluation table. RESULTS: MSG could increase the total scoring of Hagayakawa Dementia Scale and mini mental state examination (MMSE) as well as the single entry scoring of MMSE. It could reverse the process of vascular dementia in psychic evaluation table. CONCLUSION: MSG has good effect in improving intelligence and anti-dementia. PMID- 11783213 TI - [Enhancing effect of Chinese herbal medicine mixture on peripheral blood lymphocyte proliferation and interleukin-2 production in patients of burn]. AB - OBJECTIVE: To study the regulatory effect of Chinese herbal medicine mixture (CHMM) on cell-mediated immune function in patients of burn. METHODS: Patients of burn were treated with CHMM and the therapeutic effect was evaluated by their peripheral blood T-lymphocyte (PBL) proliferation and interleukin-2 (IL-2) production determination. RESULTS: The PBL proliferation began to increase after 5 days of medication and the response was significant between the 10th to 20th day, which was in accordance with the change of IL-2 production. CONCLUSION: CHMM has immune regulatory effect on cell-mediated immune function in patients of burn. PMID- 11783214 TI - [Clinical comparative observation on duodongning and Ritalin in treating child hyperkinetic syndrome]. AB - OBJECTIVE: To study the effect and side-effect of Duodongining (DDN), a Chinese herbal preparation, in treating child hyperkinetic syndrome. METHODS: Double blind method was used in observation on effect of DDN and compared with that of Ritalin. RESULTS: In the 37 patients treated with DDN, 17 (45.9%) were markedly effective and 16 (43.2%) were effective. In the 33 Patients treated with Ritalin, the respective case numbers were 15 (45.5%) and 14 (42.4%). The Conners Hyperactive Index of the DDN group before treatment was 2.01 +/- 0.83, and after treatment 1.17 +/- 0.76, while that of the Ritalin group was 2.07 +/- 0.91 before treatment and 1.47 +/- 0.79 respectively after treatment. There were no significant difference between the two groups both in effect and in Conner Index, P > 0.05. The main side-effect was lack of appetite, it revealed in 3 cases of the DDN group and 7 cases of the Ritalin group, and was severer in the latter. CONCLUSION: The effect of DDN and Ritalin were not different significantly, but the side-effect of Ritalin was severer than that of DDN. PMID- 11783215 TI - [Serapharmacological effect of fuzheng huayu 319 Decoction on expression of type I collagen and transforming growth factor beta 1 in hepatic stellate cells]. AB - OBJECTIVE: To investigate the main serapharmacological mechanism of antifibrotic action of Fuzheng Huayu 319 Decoction (FHD) at cellular and molecular level. METHODS: Hepatic stellate cells (HSC) were isolated from the normal rats and subcultured. Normal rats were medicated with FHD and their blood serum collected to prepare the medicated serum, which was incubated with the subcultured HSC. Then, the extra- and intracellular collagen synthetic rates were assayed with collagenase digestion method, type I collagen content in the medium measured with ELISA, transforming growth factor beta 1 (TGF beta 1) protein production semiquantified by immunocytochemistry stain and image analysis system, the gene expressions of type I procollagen and TGF beta 1 analyzed by RT-PCR. RESULTS: FHD medicated serum could obviously inhibit the extra- and intracellular collagen synthetic rates, decreased type I procollagen mRNA expression and its secretion, downregulate TGF beta 1 mRNA and its protein expression. CONCLUSION: FHD could inhibit HSC activation markedly, the main mechanism of its antifibrotic action may be the medicated serum inhibition on type I procollagen and TGF beta 1 gene expression. PMID- 11783216 TI - [Effect of regulation of kidney-yin and kidney-yang on hypothalamus-pituitary adrenal-thymus axis in monosodium L-glutamate rats]. AB - OBJECTIVE: To study the interrelationship between hypothalamus-pituitary-adrenal thymus (HPAT) axis and Kidney-Yang and Kidney-Yin in arcuate nucleus destroyed rats. METHODS: Monosodium glutamate (MSG) 4 mg/g body weight was given subcutaneously to neonatal rats at 2, 4, 6, 8 and 10th day after born to destroy the ARC, and Zuogui pill or Yougui pill (5 g/kg daily) was given respectively by gastrogavage when the model rats entered adulthood. RESULTS: Immunohistochemical staining showed that in the model group the number of corticotropin-releasing hormone (CRH) positive neurons in hypothalamic paraventricular nucleus and anterior pituitary adrenotrophin (ACTH) positive secretory cells, which stained deeply, were more than those in the control group, the adrenal fasciculate zone disturbed with increased cells and obviously dilated sinusoid. The thymus atrophied with lymphocyte proliferation apparently lower, blood corticosterone, ACTH content and hypothalamic CRF level higher in the model than those in the control. Zuogui pill could improve above-mentioned pathophysiologic changes effectively but Yougui pill could not. CONCLUSION: Process of pathophysiology of HPA axis hyperfunction accompanied cell-mediated immunodeficiency may belong to the category of Kidney-Yin Deficiency Syndrome. PMID- 11783217 TI - [Effect of bailong recipe on proliferation phenotype of human gastric carcinoma BGC82-3 cell line]. AB - OBJECTIVE: To observe the reversive effect of Composite Bailong recipe (BR), a preparation of Chinese herbal medicine, on proliferation phenotype of human gastric carcinoma BGC82-3 cell line. METHODS: Observation was conducted by using growth curve, colony on soft agar and nude mice oncogenesis experiment. RESULTS: Growth curve showed the proliferation of BGC82-3 cell was obviously inhibited by BR, the inhibiting rate reached 86% in the 5th day. The colony was few and small on soft agar after treated with BR, only accounted for 52% as compared with that of nontreated. BR obviously inhibited the oncogenesis of BGC82-3 cells in nude mice, the inhibition rate being 50%. CONCLUSION: Composite BR has obvious inhibiting action on malignant proliferation of human gastric BGC82-3 cell line. PMID- 11783218 TI - [Preventive effect of radix Astragali on insulin resistance caused by tumor necrosis factor-alpha]. AB - OBJECTIVE: To investigate the preventive effect of Radix Astragali (RA) on insulin resistance caused by tumor necrosis factor-alpha (TNF-alpha). METHODS: Normal rats were pretreated with RA or distilled water by intragastric infusion for one week. Glucose-insulin tolerance test was conducted in the rats 4 h after low dose TNF-alpha injection by caudal vein to estimate the change in insulin sensitivity. Meanwhile, the plasma glucagon, ACTH, blood lipid, and glycogen, triglyceride in tissue were also observed. RESULTS: Exogenous TNF-alpha could induce hyperinsulinemia in normal rats. K value in glucose-insulin tolerance test decreased, serum ACTH, glucagon, blood lipid increased, glycogen content in liver and red quadriceps muscles decreased, the liver triglyceride level increased in the TNF-alpha treated rats. RA could improve all the above-mentioned changes significantly except the blood lipid and triglyceride depots in liver. CONCLUSION: RA has obvious preventive effect on insulin resistance caused by TNF alpha, it may be due to its action in decreasing insulin antagonistic hormones and increasing glycogen synthesis in tissue. PMID- 11783219 TI - [Integrated traditional Chinese medicine and Western medicine in the prevention and treatment of malignant tumor in 21st century]. PMID- 11783220 TI - [Significance of aldose-reductase inhibition with traditional Chinese and Western drugs in the treatment of diabetic peripheral neuropathy]. PMID- 11783221 TI - [Clinical and experimental studies on huodan tablet in treating pediatric viral myocarditis]. AB - OBJECTIVE: To study the effect of Huodan Tablet in treating pediatric viral myocarditis. METHODS: Clinical manifestations and physical signs as well as laboratory examinations have been observed. RESULTS: The markedly effective rate was 68%, the total effective rate was 91.67% in therapeutic group, while in control group, the markedly effective rate was 30.83% and the total effective rate 70.84%. According to Ridit analysis, significant difference was shown between the two groups. r-therapeutic group = 0.5000, r-control group = 0.295 + 2 x 0.025, respectively. CONCLUSION: Huodan Tablet has no toxic and side-effect and can be taken safely and conveniently, it complies with the demands of WHO on new drug for prevention and cure of myocarditis. PMID- 11783222 TI - [Clinical observation on treatment of 304 patients suffered from acute myocardial infarction with integrated Traditional and Western Medicine]. AB - OBJECTIVE: To make a retrospective survey study on clinical effect and regular pattern of TCM treatment based on Syndrome Differentiation in treating patients of acute myocardial infarction (AMI), admitted in Xiyuan Hospital from January 1978 to December 1997 with integrated traditional Chinese and western medicine. METHODS: Statistical analysis was made in the following items of 304 patients: age, sex, location of infarction, complication, cause of death, mortality, as well as TCM Syndrome, principle of treatment, prescription and medicinal herbs used. RESULTS: The incidences of complications in this group for arrhythmia, pump failure, thrombosis were 68.75%, 36.84% and 0.66% respectively, while those in patients treated with western medicine reported by literature in China were 86% 100%, 50% and 2% respectively. Mortality in this group after using thrombolytic therapy was reduced from 17.32% (35/202) to 10.78% (11/102). Types of disease, according to Syndrome Differentiation of TCM, were mainly the Qi-deficiency type, blood stasis type and turbid-phlegm type. And the principle of TCM treatment was mainly to supplement Qi, activate blood circulation and resolve phlegm. CONCLUSION: Integrated traditional Chinese and western medicine treatment of AMI could reducing incidence of complications, such as arrhythmia, pump failure and thrombosis, and thrombolytic therapy could reduce mortality of patients. The frequently encountered TCM Syndrome types and the corresponding therapeutic methods and prescriptions used in treating AMI have also been summarized in this paper. PMID- 11783223 TI - [Clinical observation on 51 patients of acute myocardial infarction treated with thrombolytic therapy combined with Chinese herbal medicine]. AB - OBJECTIVE: To assess the efficacy of thrombolytic therapy combined with Chinese herbal medicine (CHM) in treating acute myocardial infarction (AMI). METHODS: One hundred and one cases of AMI were divided randomly into two groups. The treated group treated with thrombolytic therapy combined with CHM and the control group treated with thrombolytic therapy alone. The criteria of patency of coronary artery were conducted according to the referential standard of thrombolytic therapy in treating AMI introduced by Chinese Angiocardiopathy Medical Journal, 1991. RESULTS: The patency rate of coronary artery of the two groups were 68.63% and 56.00%, the four-week mortality 3.92% and 10.00%, hemorrhage occurrence 1.96% and 10.00%, congestive heart failure occurrence 5.88% and 16.00%, severe arrhythmia occurrence 11.76% and 22.00%, and the shock occurrence 3.92% and 8.00% respectively. The difference between the two groups was significant, P < 0.01, P < 0.05. CONCLUSION: The effect of the treated group was better and the complication occurrence of the treated group was lower than those of the control group. PMID- 11783224 TI - [Relationship between endothelins, nitric oxide and other endothelial active factors and blood stasis syndrome in patients with atherosclerosis obliterans]. AB - OBJECTIVE: To observe the levels of plasma endothelin (ET), nitric oxide (NO), intercellular adhesion molecule (ICAM) and other endothelial active factors, and to investigate the nature of atherosclerosis obliterans (ASO)-blood stasis Syndrome (BSS) from the point of vascular endothelia and molecules. METHODS: Ninety-eight patients with ASO-BSS were divided into 3 groups (mild, moderate and severe) and 3 clinical Syndrome subtypes (Qi stagnation BSS, Qi deficiency BSS and Damp-Heat BSS). The circulating endothelial count (CEC), ET, NO and other plasma active factors were determined by density gradient method, radioimmunoassay, enzyme immunoassay method. RESULTS: The patients with ASO-BSS had high CEC and ET levels, low levels of NO, and had alterations of hemorheology, particularly in those with severe BSS and Damp-Heat BSS. CONCLUSION: ASO-BSS patients have endothelial injuries, endothelial dysfunction, and alterations of hemorheology, which may be the pathogenetic mechanism of ASO BSS. Observation on these parameter changes will be helpful to evaluate severity, to distinguish the clinical types in TCM, and to clarify the nature of BSS. PMID- 11783225 TI - [Clinical study on effect of Chinese herbal medicine for supplementing kidney and qi and activating blood circulation in treating intrauterine growth retardation of fetus]. AB - OBJECTIVE: To explore the therapeutic effect and its possible mechanism on using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). METHODS: Fifty-five cases of IUGR were observed, 30 of them were treated with CHM and 25 treated with amino acid for control. RESULTS: The neonatal birth weight in the CHM group was markedly greater than that in the control group. Not only the maternal fundal height and abdominal circumference, but also the fetal growth parameters, including biparietal diameter, head circumference, abdominal circumference, femur length in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) were close to the normal pregnancy group, but the levels in the control group were significantly different from the normal range. The umbilical venous plasma concentration of essential amino acids was markedly improved after treatment, however, the improvement in the CHM group was more significant than that in the control group. No adverse effect of CHM was found both in mother and fetus. CONCLUSION: CHM for supplementing Kidney and Qi, and activating blood circulation was more effective in the improvement of placental function and amino acid transportation than those of amino acid. PMID- 11783226 TI - [Clinical study on treatment of mid-late stage gastric carcinoma by composite xiansu capsule combined with chemotherapy]. AB - OBJECTIVE: To assess the effect and mechanism of composite Xiansu Capsule (CXSC) combined with chemotherapy in treating gastric carcinoma of mid-late stage. METHODS: The 61 patients of the test group were treated by CXSC combined with chemotherapy and 30 patients of the control group treated with chemotherapy alone. The effect of treatment and cell mediated immunity of patients were observed. RESULTS: The effective rate of the test group and the control group was 32.8% and 13.3% respectively (P < 0.05), the chemotherapy caused toxic reaction occurrence was less in the former than that in the latter group (P < 0.01). The CD3 level of patients in the test group was decreased, and CD4/CD8 level was raised obviously, which suggested that CXSC had immuno-regulating effect on T cells. CONCLUSION: CXSC could enhance the efficacy and reduce the toxic side effect of chemotherapy. To regulate the cell mediated immunity of patients is possibly its mechanism. PMID- 11783227 TI - [Ailing No. I in treating 62 cases of acute promyelocytic leukemia]. AB - OBJECTIVE: To obtain further knowledge on the effect, mechanism and toxic side effect of Ailing No. I (AL), a preparation of As2O3, in treating acute promyelocytic leukemia (APL). METHODS: AL was used in induction and consolidation treatment of 62 cases of APL, the effect of treatment and the changes of clinical symptoms, peripheral blood and bone marrow pictures, T-lymphocyte subset, and immunofunctions of patients after treatment were observed. RESULTS: Twenty-seven cases out of the 31 patients who received induction treatment got complete remission (CR), the CR rate being 87.1%. Of the 31 cases who received consolidation treatment, the longest remission period was 37 months, and 7 cases relapsed within one month to 2 years. Peripheral white blood cell count raised after one week but lowered after 4 weeks of induction treatment, but in receiving consolidation treatment, it started to lower after one week and raised after 4 weeks of treatment. No obvious change on hemoglobin level was observed. Platelet count significantly increased after treatment. The treatment showed no obvious inhibition on bone marrow. The T-lymphocyte subsets and immunoglobulin level were changed insignificantly after treatment. Various side-effects were shown clinically, particularly those digestive tract involved symptoms were prominent, and liver damage was shown in a certain degree. CONCLUSION: AL has good and protracted effect in treating APL with high CR rate, the mechanism may be related with its cytotoxicity and action of differentiation induction. PMID- 11783228 TI - [Clinical and experimental study on treatment of chronic pyogenic tympanitis with shenlian ear-drops]. AB - OBJECTIVE: To study the effect and mechanism of Shenlian Ear-Drops (SLED), a composite preparation of Chinese herbal medicine, in treating chronic pyogenic tympanitis (CPT). METHODS: The 201 patients of CPT enrolled were divided randomly into two groups. The treated group were treated with SLED, three times per day, and the control group treated with ofloxacin ear-drop, three times per day. The changes in symptoms, signs and bacterial culture after treatment were observed. Experimental studies on anti-inflammatory, detumescent effect and skin mucosa irritation test, and bacteriostasic activity of SLED were also conducted. RESULTS: The curative effect in the treated group was higher than that in the control group with shorter time of medication. The improvement of symptoms and signs in the former was also better than that in the latter (P < 0.05 or P < 0.01). Experimental study showed SLED had obvious anti-inflammatory and detumescent effect, apparent bacteriostasic activity against often encountered pathogens of CPT, and with no side-effect such as irritation on skin, mucosa of external acoustic meatus or tympanic cavity, and was non-ototoxic. CONCLUSION: SLED has good curative effect in treating CPT. PMID- 11783229 TI - [Experimental studies on improving heart preservation effect of Astragalus saponins]. AB - OBJECTIVE: To observe the effect of heart preservation of Astragalus saponins (AS) in modified Euro-Collins solution (mEC) containing AS. METHODS: Wistar rats were randomly divided into mEC and AS group. After preserving isolated rat hearts 6 hours by simple cold storage with mEC and mEC containing AS respectively, Langendorff's isolated rat heart model was used to reperfuse for 30 minutes to study cardiac function after preservation and the effect of preventing oxygen free radical injury. RESULTS: To compare AS group with mEC group, cardiac function and coronary flow of the hearts after preservation were better than mEC group (P < 0.05), in AS group the water content of myocardium was decreased very significantly (P < 0.01), myocardial lactate dehydrogenase and creatine phosphokinase release were reduced greatly (P < 0.05 and P < 0.01), myocardial superoxide dismutase activity was increased very significantly (P < 0.01) and the content of lipid peroxide was decreased significantly (P < 0.05). CONCLUSION: AS could improve the effect of heart preservation of mEC solution, its mechanism might be associated with the effect of negative contractile strength and preventing oxygen free radical injury. PMID- 11783230 TI - [Effect of Astragalus Angelica Mixture on lipoprotein lipase and lecithin cholesterol acyltransferase of nephrotic rats]. AB - OBJECTIVE: To investigate the mechanism of Astragalus Angelica Mixture (AAM) effect of regulating lipid metabolism disturbance in nephrotic rats. METHODS: To examine the effects of AAM on serum albumin, lipid levels, and activities of lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT), which are key enzymes for catabolism of lipid, in immune-induced nephrotic hyperlipidemia rats and exogenous hyperlipidemia rats. RESULTS: Serum albumin was reduced, lipid increased significantly, LPL activity decreased significantly and the LCAT activity was relatively insufficient in nephrotic rats. Activities of LPL and LCAT increased significantly in AAM treated nephrotic rats. There were no change of activities of LPL and LCAT in exogenous hyperlipidemia rats and AAM showed no effect on the activities of these two enzymes. CONCLUSION: The effect of AAM in regulating lipid metabolism might be due to enhancing the clearance of triglyceride and cholesterol-rich lipoprotein by improving the activities of LPL and LCAT. PMID- 11783231 TI - [Effects of kidney nourishing and spleen invigorating recipes on glucocorticoid receptors of pulmonary tissue and plasma corticosterone in asthmatic rats]. AB - OBJECTIVE: To observe the effects of Guiqi San (GQS, a Chinese herbal preparation with effect of Kidney Nourishing and Spleen Invigorating), Bushen Dingchuan Tang (BSDCT, with effects of Kidney Nourishing) and Liujunzi Tang (LJZT, with effect of Spleen Invigorating) on glucocorticoid receptor (GCR) and plasma corticosterone (PCC) in asthmatic rats. METHODS: The asthmatic model of rats made by intraperitoneal injection of ovalbumin two weeks before, and the asthma consecutively challenged daily with spray inhalation of 1% ovalbumin for 7 days. The asthmatic rat treated with above-mentioned three recipes (per os) and Beclomethasone dipropionate (BDP) were taken as treated groups and the asthmatic rat as control group. GCR density of the pulmonary tissue and PCC were determined by radioligand-binding assay and competitive protein radio-binding assay. RESULTS: The RT value of GCR reduced gradually and PCC lowered also after asthma being developed. On day 7th, the three recipes could markedly up-regulate the RT of GCR and PCC. There was significant difference statistically as compared the pulmonary tissue GCR density and PCC of GQS (P < 0.01, P < 0.05), BSDCT (P < 0.05, P < 0.05) and LJZT (P < 0.05, P < 0.05) groups with those of control (asthmatic group) on the 7th day. CONCLUSION: GQS, BSDCT and LJZT played an up regulate role of GCR density and improvement of adrenocortical function in asthmatic rats in the management of asthma attacks. PMID- 11783232 TI - [On the upperstream and downstream engineering projects in developing Chinese new drugs]. PMID- 11783233 TI - [Current status of pain relief with Chinese herbal drugs in patients with cancer]. PMID- 11783234 TI - [Review on experimental studies of Chinese drugs in antagonizing bone marrow inhibition caused by chemicals]. PMID- 11783235 TI - [Trends of research on immunology of Chinese materia medica]. PMID- 11783236 TI - [Cell differentiation and apoptosis of tumor cells]. PMID- 11783237 TI - [Relationship of cytokines and cold-heat syndrome differentiation in patients of duodenal ulcer]. AB - OBJECTIVE: To explore the relationship of cytokines and Cold-Heat Syndrome in patients of duodenal ulcer. METHODS: Cold-Heat Syndrome Differentiation was done in 48 patients of duodenal ulcer, and the levels of interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor (TNF), malonyldialdehyde (MDA), marrow peroxidase (MPO) in gastric mucosa biopsy were measured and compared with those of 10 normal subjects. RESULTS: Levels of IL-8, TNF, MPO and MDA in Heat Syndrome were higher than those in Cold Syndrome (P < 0.05), while IL-6 level showed no significant relationship with Cold-Heat Syndrome. CONCLUSION: Cytokines IL-8, TNF, MPO and MDA are correlated with Cold-Heat Syndrome in duodenal ulcer patients and which might be one of the molecular mechanisms of Cold-Heat Syndrome Differentiation. PMID- 11783238 TI - [Effect of sijunzi decoction on serum soluble intercellular adhesive molecule-1, interleukin-15 and monocyte antibody-dependent cell-mediated cytotoxicity in patients of spleen-deficiency]. AB - OBJECTIVE: To study the effect of Sijunzi Decoction (SJZD) on serum soluble intercellular adhesive molecule-1 (sICAM-1), interleukin-15 (IL-15) and monocyte antibody-dependent cell-mediated cytotoxicity (ADCC) in patients of Spleen Deficiency. METHODS: Serum sICAM-1, IL-15 and monocyte ADCC of 66 Spleen Deficiency patients were determined by enzyme-linked immunosorbent assay and modified thiazole blue test. RESULTS: Serum sICAM-1 of Spleen-Deficiency patients increased, IL-15 secretion decreased and monocyte ADCC function reduced, which displayed as lowered immune function. After SJZD treatment, all the above mentioned parameters were normalized. CONCLUSION: SJZD could enhance immune function of organism by strengthening Spleen and tonifying Qi. PMID- 11783239 TI - [Clinical study on preventive effect of taozhi zhipu mixture on postoperative intestinal adhesion]. AB - OBJECTIVE: To study the clinical effect of Taozhi Zhipu Mixture (TZM) in preventing postoperative intestinal adhesion. METHODS: Three hundred and ninety six patients who had received abdominal operation were randomly divided into the treated group (188 cases) and the control group (208 cases). Same treatment was given to both groups excepting that the treated group received TZM orally or by nasogastric tube. The time of borborygmus recovering and first passing of flatus defecation after operation was recorded. Patient's gastro-intestinal motion was observed by isotope tracing with I131 capsule. The frequency and intensity of borborygmus were measured by a tracer. All patients had been followed up for 2-3 years. RESULTS: The recovery of borborygmus, the first passing of flatus defecation were much earlier, the I131 capsule passed gastro-intestinal tract more quickly, and tracer showed higher frequency and intensity of borborygmus in the treated group than those in the control group. Follow-up study also showed the treated group was better than the control group in the non-adhesion rate and the total effective rate (P < 0.05). CONCLUSION: TZM has good effect on stimulating postoperational gastro-intestinal peristalsis and preventing the occurrence of postoperational intestinal adhesion. PMID- 11783240 TI - [Clinical study on effect of Chinese herbal medicine on liver damage caused by hepatic artery chemoembolization]. AB - OBJECTIVE: To observe the effect of Chinese herbal medicine on hepatic artery chemoembolization caused liver damage. METHODS: One hundred and ten patients, who received hepatic artery chemoembolization, were divided into two groups, 60 patients in the treated group were treated with Qinggan Jiedu Sanjie Decoction and the other 50 Patients in the control group treated with routine western medicine. The changes of liver function, cirrhosis incidence and exacerbation rate of both groups were observed. RESULTS: The total liver function deterioration rate of the treated group, according to Child's grading standard, was 46.67%, while that of the control group was 68.00%, the former was much lower than the latter (P < 0.05). The cirrhosis incidence and exacerbation rate in the treated group were 35.00% (7/20) and 50.00% (20/40) respectively, while in the control group, they were 65.00% (13/20) and 76.67% (23/30) respectively. The difference between the two groups was also significant (P < 0.05). CONCLUSION: Qinggan Jiedu Sanjie Decoction has some effect on alleviating and preventing hepatic damage caused by hepatic artery chemoembolization. PMID- 11783241 TI - [Study on essence of syndrome of traditional Chinese medicine in liver cirrhotic patients]. AB - OBJECTIVE: To explore the essence of Syndrome of traditional Chinese medicine (TCM) in cirrhostic patients. METHODS: Eighty patients of post-hepatitis-B cirrhosis were classified, according to Syndrome Differentiation of TCM, into three types: the Liver-Qi Stagnancy and Spleen-Deficiency type (A), the Qi Stagnancy and blood stasis type (B) and the Heat Stagnancy and blood stasis type (C), serum hyaluronic acid (HA), adenosine deaminase (ADA), glutathione-s-epoxide transferase (GST), N-acetyl-beta-D-glucosaminidase (NAG), hydroxyproline (HYP) and procollagen type III (PC III) of 52 patients were determined before and after treatment based on Syndrome Differentiation. RESULTS: Serum HA, ADA, GST and PC III of patients were significantly higher than those of the healthy control (P < 0.01), and the change of these parameters were closely associated with types of Syndrome, which were, in turn, C > B > A > control, the difference between groups was significant (P < 0.05, P < 0.01). After treatment, the liver function and above-mentioned serologic parameters were significantly improved (P < 0.05, P < 0.01). CONCLUSIONS: Syndrome of cirrhosis patients has its inherent essential content. Serum HA, ADA, GST and PC III could serve as objective indexes for establishing Syndrome Differentiation and guiding treatment. TCM treatment of cirrhosis based on Syndrome Differentiation has good effect with beneficial anti fibrotic action. PMID- 11783242 TI - [Effect of Angelica sinensis injection on CD11c and CD14 expression in alveolar macrophage membrane of chronic bronchitis patients]. AB - OBJECTIVE: To explore the effect of Angelica sinensis injection (ASI) in CD11c and CD14 expression in alveolar macrophage (AM) membrane of chronic bronchitis patients. METHODS: AM from 10 chronic bronchitis patients (remmision stage) and 10 healthy subjects was obtained by bronchoalveolar lavage. After had cultured for 24 hours with ASI or/and lipopolysaccharide (LPS), CD11c and CD14 expression and intracellular calcium ion concentration in AM were analyzed by flow cytometry. RESULTS: CD11c and CD14 expression levels of patients' AM membrane (n = 10) were (39.17 +/- 5.56)% and (35.73 +/- 8.05)% respectively, which were significantly higher than those of the control [n = 10, (16.29 +/- 3.78)% and (15.26 +/- 5.96)%], P < 0.05. LPS could increase the elevation of CD11c expression of patients [(47.25 +/- 7.00)%, P < 0.05], while ASI could reduce the increment [LPS Plus ASI group (27.61 +/- 8.64)%, P < 0.05]. The basic calcium level of AM cytoplasma of patients was (189.47 +/- 23.69) nmol/L (n = 7), which was higher than that of healthy control (99.65 +/- 32.21) nmol/L (n = 6), P < 0.05. The intracellular calcium ion elevation in AM of patients could be induced by LPS, and ASI could inhibit the elevation. The calcium level in LPS group was (288.47 +/- 43.68) nmol/L, in ASI Plus LPS group, (236.68 +/- 28.60) nmol/L, P < 0.05. CONCLUSIONS: ASI could reduce the CD11c expression in AM of chronic bronchitis patients by inhibiting LPS induced intracellular calcium ion elevation in AM, suggesting that ASI may inhibit non-specific inflammation of respiratory tract. PMID- 11783243 TI - [Effect of composite salviae dropping pill on endothelin gene expression in circulating endothelial cells of patients with coronary heart disease]. AB - OBJECTIVE: To explore the effect of composite salviae dropping pill (CSDP) on endothelin (ET-1) gene expression in circulating endothelial cells. METHODS: Seventy cases of stable angina pectoris were randomly divided into 2 groups, the CSDP group and the isosorbide dinitrate (ID) group. They were treated with CSDP and ID respectively, their ET-1 gene expression in endothelial cells of peripheral circulation was measured before and after treatment by reverse transcriptase-Polymerase Chain Reaction and compared between the two groups as well as with that of 30 healthy subjects. RESULTS: Electrophoresis banding of 546 bp cDNA procured from 69 cases of 70 patients was positive, while no positive banding was obtained from healthy subjects. Six cases from the 29 patients treated with CSDP had their banding turned to negative, while in the ID group, no one had turned to negative after treatment. And ET-1 PCR product (absorbed optic density) in the CSDP group was markedly lower than that in the ID group, P < 0.05. CONCLUSION: DSP could inhibit ET-1 gene expression in endothelial cells of peripheral circulation directly. PMID- 11783244 TI - [Effect of xuefu zhuyu decoction on function of platelet and endothelial cell]. AB - OBJECTIVE: To explore the effect of Xuefu Zhuyu Decoction (XFZYD) on function of platelet and endothelial cell. METHODS: Through incubation of XFZYD, in different concentration, with platelet and human umbilical vein endothelial cell, the platelet membrane glycoprotein II b/III a complex and thrombomoduline (TM) of human umbilical vein endothelial cell were determined by radioimmunoassay. RESULTS: XFZYD in 40 mg/ml or 80 mg/ml could obviously inhibit the adenosine diphosphate induced glycoprotein II b/III a molecular expression, as compared with the control group, the difference was significant (P < 0.05, P < 0.01), but it did not influence the TM level significantly. CONCLUSION: XFZYD could inhibit the adenosine diphosphate induced activation of platelet through blocking the exposure of glycoprotein II b/III a complex. PMID- 11783245 TI - [Study on preventive and therapeutic effect of radix salviae miltiorrhizae on recurrence and metastasis of liver cancer]. AB - OBJECTIVE: To study the inhibitory effect of Radix Salviae Miltiorrhizae (RSM) on adhesive and invasive ability of SMMC-7721 liver cancer cells, and on the metastasis and recurrence on post-hepatectomy liver cancer in nude mice. METHODS: Effect of RSM on SMMC-7721 cell membrane intercellular adhesive molecule-1 (ICAM 1) expression was observed by immunofluorescence flow cytometry; effect on invasive ability and of SMMC-7721 cell and the detachment of which attached to fibronectin (FN) by cell migration experiment; effcet on adhesion of SMMC-7721 cell with FN by MTT method and effect on adhesion between 7721-7721, 7721 lymphocyte and 7721-endothelial cell by cell adhesion experiment. LCI-D20 human liver cancer metastasis model, after hepatectomy, was used to observe the effect of RSM on recurrence and metastasis of liver carcinoma in nude mice. RESULTS: ICAM-1 expression in SMMC-7721 cells incubated with RSM was significantly lower than that in cells did not treated with RSM. RSM could inhibit the invasive ability of SMMC-7721 cell and made the cells already attached to FN exfoliated. It could also inhibit the adhesion of 7721-7721, 7721-lymphocyte and 7721 endothelial cell. And RSM showed preventive and therapeutic effect on intrahepatic and remote metastasis/recurrence of early and late human post hepatectomy liver cacer in nude mice. CONCLUSION: RSM could inhibit the invasion and adhesion of SMMC-7721 cell and could also prevent and inhibit metastasis and recurrence of human liver cancer after hepatectomy in nude mice. PMID- 11783246 TI - [Experimental study on apoptosis induced by ursolic acid isolated from asparagus in HL-60 cells]. AB - OBJECTIVE: To study the inhibitory effect of ursolic acid isolated from Asparagus on the proliferation of HL-60 cells. METHODS: Effects of ursolic acid on the growth and apoptosis were evaluated by MTT assay, DNA gel electrophoresis and morphology observation respectively. RESULTS: The IC50 value of ursolic acid for HL-60 cells was found to be 8.26 mumol/L and 10-50 mumol/L of ursolic acid could induce apoptosis of HL-60 cells expressed to ursolic acid for 1 day. CONCLUSION: Ursolic acid can markedly inhibit HL-60 cells as well as induction of cells apoptosis. PMID- 11783247 TI - [Effect of shenshuaining on proliferation and autocrine interleukin-1 secretion of human mesangial cells]. AB - OBJECTIVE: To explore the effect of Shenshuaining (SSN), on the proliferation of human mesangial cells (HMC) and the autocrine secretion of interleukin-1 (IL-1). METHODS: SSN, a preparation of Chinese herbal drug having actions of Qi supplementing, origin consolidation, blood stasis resolving and turbid substance removing, medicated serum of animal was extracted by pharmacologic method and its effect on proliferation and autocrine IL-1 secretion of HMC was observed. RESULTS: SSN could inhibit the proliferation and IL-1 autocrine secretion of HMC, and the inhibition was dose-dependent. CONCLUSION: Mesangial cell is the important target cell for action of SSN, the inhibition on HMC may be one of the mechanisms of SSN in prevention and treatment of chronic renal failure. PMID- 11783248 TI - [Experimental study on protective effect of Chinese herbal medicine on glucocorticoid receptor]. AB - OBJECTIVE: To probe the relationship of glucocorticoid receptor and some Chinese medicinal herbs. METHODS: The models of Qi-Yang exhaustion and Qi-Yin exhaustion were made with hemorrhagic rats and heat-stressed rats respectively. The effect of Shenfu Decoction (SFD) and Shengmai Powder (SMP) on plasma glucocorticoid (GC) and its receptor (GcR) in hepatic cytosol of the models were measured respectively. RESULTS: The activity of GcR decreased in both models, while their blood level of GC increased markedly. SFD and SMP showed no regulating effect on blood GC, but displayed obvious up-regulation on GcR level in both models. CONCLUSION: SFD and SMP could up-regulate the activity of GcR in Qi-Yang and Qi Yin exhaustion models. PMID- 11783249 TI - [Research on the clinical evaluation of Chinese materia medica in view of international quality control]. PMID- 11783250 TI - [Auriculo-acupoint diagnosis and its development]. PMID- 11783251 TI - [Clinical study on effect of shenqi fuzheng injection combined with chemotherapy in treating gastric cancer]. AB - OBJECTIVE: To assess the clinical effect of Shenqi Fuzheng Injection (SQFZI) combined with chemotherapy in treating gastric cancer. METHODS: One hundred and twenty patients were randomly divided into 3 groups, the combined therapy group (Group A), the chemotherapy group (Group B) and the SQFZI group (Group C) and the effect on remission and stabilization of patients were observed. RESULTS: The remission rate and stabilizing rate of Group A were 16.1% and 87.1%, those of Group B were 13.5% and 64.9%, the difference between the two groups was significant, P < 0.05. The symptom and living quality improving rate of Group A were 75.8% and 43.5% respectively, those of Group C were 61.9% and 57.1% and of Group B were 35.1% and 29.7% respectively. SQFZI showed good protective effect on hemopoietic system, 4.8% patients in Group A with WBC count lower than 4 x 10(9)/L, while the percentage reached 21.6% in Group B, the difference between the two groups was significant, P < 0.05. Moreover, SQFZI could raise activity of NK cell, macrophage and T-lymphocyte subgroups, without any injury on heart, liver and kidney function or other adverse reaction. CONCLUSION: SQFZI combined with chemotherapy has certain effect of remission and stabilization on gastric cancer, the clinical effect is significant to patients with Qi-Deficiency, and is reliable and safe. PMID- 11783252 TI - [Clinical observation and experimental study on treatment of malignant tumor with bailong tablet]. AB - OBJECTIVE: To observe the clinical efficacy of treating moderate and advanced malignant tumors with the compound Chinese herbal medicine, Bailong tablet (BLT) and to explore its mechanism. METHODS: Therapeutic effect of BLT in treating 34 cancer patients was analyzed according to the criteria of therapeutic effect for solid tumor, and changes on their living quality and immune function were observed clinically. In the experimental studies, the effect of BLT on human lymphocyte, celiac macrophage of mice and human gastric cancer cells in vitro were observed. RESULTS: The total remission rate was 11.8%, the remission stationary rate was 82.3%, the living quality improved and immune function of organism enhanced, the difference between before and after treatment was significant (P < 0.05 or P < 0.01). Experimental study revealed that comparing with the control group, BLT can induce the activated human lymphocyte to kill target cell, promote the proliferation of T-lymphocyte, activate the phagocytosis of celiac macrophage in vitro(P < 0.05 or P < 0.01). CONCLUSIONS: BLT has definite therapeutic effect for moderate and advanced cancer, its anti-tumor effect was related to a series of cell biologic mechanisms, such as the immune function enhancement, T-lymphocyte proliferation and macrophage activation. PMID- 11783253 TI - [Potentiated effects of total saponins of Panax Ginseng on inhibition of leukemic cells by cytotoxic drugs]. AB - OBJECTIVE: To investigate the potentiated effects of total saponins of Panax Ginseng (TSPG) on inhibition of leukemic progenitor cells by cytotoxic drugs in acute myelocytic leukemia. METHODS: Using bone marrow culture of colony forming unite-acute myeloid leukemia (CFU-AML) method, the sensitivity of leukemic cells obtained from 18 patients to homoharringtonin (HHr), cytarabine (Ara), adriamycin (Adr) and etoposide (VP-16) were detected separately. RESULTS: TSPG alone (20 micrograms/ml) could stimulate proliferation of CFU-AML obviously, and increase the colony numbers by 37.98% over the non-TSPG control (P < 0.01). In the presence of TSPG, the inhibition rates of CFU-AML of HHr, Ara, Adr and VP-16 were 51.2%-62.0% respectively, which were significantly higher than 30.4%-47.4% of non TSPG control (all P < 0.01). In the combination of TSPG with cytotoxic drugs, the leukemic progenitor cells became more sensitive to cytotoxic drugs, CFU-AML colony numbers at 1.84-2.23 fold as more as those of non-TSPG control were inhibited by HHr, Ara, Adr and VP-16. Sensitivity test of 17 among 72 drugs reversed from resistant (suppression rate less than 30%) to sensitive (suppression rate more than 30%) by TSPG. CONCLUSIONS: TSPG could drive non cycling leukemic progenitors to enter cell cycle, and thereby enhance their susceptibility to cytotoxic drugs. PMID- 11783254 TI - [Clinical observation on treatment of 38 cases of postoperational large intestinal cancer by fuzheng yiai decoction combined with chemotherapy]. AB - OBJECTIVE: To investigate the clinical value of Fuzheng Yiai Decoction (FZYAD) in postoperational large intestinal Cancer after treatment. METHODS: Thirty-eight cases treated by FZYAD combined with chemotherapy in the treated group were observed and compared with 30 patients in the control group treated with chemotherapy alone. RESULTS: After treatment, patients' physical strength of the treated group was better than that of the control group (P < 0.01), meanwhile, the median survival time was longer (31.4 months vs 18 months, P < 0.01), the survival rate higher (P < 0.05), and the recurrence rate lower (21.05% vs 48.34%, P < 0.05) in comparison of the treated group and the control group. Moreover, the cellular immune function of the treated group was improved after treatment. CONCLUSIONS: In treatment of postoperational large intestinal cancer, the effect of FZYAD combined chemotherapy is better than that of chemotherapy alone in immune function regulation, cancer inhibition, relapse prevention and survival time prolongation. PMID- 11783256 TI - [Effect of integrated Traditional Chinese and Western medicine on immune function in patient of acute cerebral infarction]. AB - OBJECTIVE: To investigate the change of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) in acute cerebral infarction patients treated with integrated traditional Chinese and western medicine (TCM-WM). METHODS: Serum sVCAM-1 level of patients treated with TCM-WM or western medicine alone was measured by ELISA, and compared with that of healthy person. RESULTS: TCM-WM could reduce the sVCAM-1 level in patients with cerebral infarction (P < 0.05). The therapeutic effect of TCM-WM was better than that of western treatment alone, P < 0.05. CONCLUSION: The therapeutic mechanism of TCM-WM may be related with the modulation on immune status of patients. PMID- 11783255 TI - [Clinical study on therapeutic mechanism of Sini Decoction in treating post percutaneous transluminal coronary angioplasty ischemia-reperfusion injury in terms of syndrome typing of TCM]. AB - OBJECTIVE: To study the mechanism of Sini Decoction (SND) in prevention and treatment of post-percutaneous transluminal coronary angioplasty (PTCA) ischemia reperfusion injury with different Syndrome typing of TCM. METHODS: Forty patients received PTCA were randomly divided equally into the SND group and the control group, in each group, there were 10 of Excess Syndrome (ES) and 10 of Deficiency Syndrome (DS). Twenty-five ml of SND was given daily to the SND group from 3 days before operation to the third day after operation. The blood superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content of patients were determined before PTCA, and 1 hrs, 12 hrs, 24 hrs, 48 hrs and 72 hrs after PTCA. RESULTS: Before PTCA, the cases of DS were characterized by low SOD activity and high MDA content, as compared with the patients of ES, P < 0.05. SND could relieve the post-PTCA deprivation of SOD activity and NO content and the elevation of MDA level of both ES and DS patients, the amplitude of elevation of SOD activity in DS patients was higher than that in ES patients (P < 0.05). CONCLUSION: SND has antagonisting effect on post-PTCA ischemia-reperfusion injury, which is more effective in treating patients with DS. PMID- 11783257 TI - [Clinical study on treatment of chronic idiopathic thrombocytopenic purpura by Decoction of Nourishing Blood and Eliminating Purpura]. AB - OBJECTIVE: To observe the clinical effect of treatment of chronic idiopathic thrombocytopenic purpura (CITP) by Decoction of Nourishing Blood and Eliminating Purpura (DNBEP), and study the possible mechanism. METHODS: Effect of 55 patients of CITP in treatment group treated by DNBEP and 22 patients in the control group treated by Antaisu were observed and compared. Their immunologic indexes were determined for exploring the mechanism. RESULTS: The markedly effective, improved and total effective rate of the treatment group were 32.7%, 20.0% and 87.3%, while those of the control group were 4.5%, 9.1% and 45.5% respectively, the difference between the two groups was significant (P < 0.001). The effect of the treatment group was better than the control group in platelet count restoring, hemorrhagic symptoms improving and effect initiating, P < 0.01. Immunologic test showed that the humoral and cell immune function as well as platelet function were abnormal in CITP patients. These functions were improved after treatment, and the effectiveness of the treatment group was significantly superior to that of the control group. CONCLUSIONS: DNBEP is reliable in treating CITP clinically. Its mechanism might be better due to its selective suppression of humoral immune function, bi-directional regulation of cell immune function and recovery of platelet function. PMID- 11783258 TI - [Effect of kidney deficiency caused by ovariectomy on serum osteocalcin level and tumor necrosis factor in mice with collagen induced arthritis]. AB - OBJECTIVE: To explore the effect of ovariectomy caused Kidney Deficiency on the metabolism of bone in mice with collagen induced arthritis. METHODS: The mice for experiment were immunized with subcutaneous injection of type II collagen to induce arthritis after ovariectomy. Severity of joint swelling, radioimmunoassay of serum estradiol (E2), osteocalcin (OC) and tumor necrosis factor (TNF), and pathological changes of joint, including changes on synovia, articular cartilage and bone, were observed once weekly. RESULTS: The E2 level of ovariectomized mice dropped down obviously, while the contents of OC and TNF increased significantly. Severe pathological changes can be seen in synovial tissues, cartilage and bone. CONCLUSION: Kidney Deficiency caused by ovariectomy exacerbated the pathological changes of collagen-induced arthritis in mice. PMID- 11783259 TI - [Experimental study on anti-cancer effect of Cantharidine derivatives and platinum complex]. AB - OBJECTIVE: To certify the anti-tumor effects of the four Cantharidine derivatives and platinum complex on transplanted tumor in mice to search for new anti-tumor drugs. METHODS: Complex of four Cantharidine derivatives (Dpt 1-15, Dpt 5-10, Dpt 12-3 and Dpt6-2) and platinum were given to tumor beating mice of transplanted S180 sarcoma, H22 solid hepatocarcinoma and ascites hepatocarcinoma through intraperitoneal or intravenous injection, and the effect of treatment on tumor weight and survival of animal were observed. Cisplatin was used as positive control and 0.9% normal saline used as negative control. All data were treated with t test. RESULTS: All the four complex had anti-tumor effect. The inhibition rate of Dpt5-10 and Dpt1-15 on S180 sarcoma and H22 solid hepatocarcinoma and the survival prolongation rate of Dpt5-10 on H22 ascites hepatocarcinoma were similar to those of cisplatin. The toxicity of effective dose of Dpt1-15 was rather high. CONCLUSIONS: Cantharidine derivatives and platinum complex is new effective anti tumor drug, among them the Dpt5-10 is the most effective one. Further study for improving the solubility of drug is necessary and study the difference of cross resistance between the new complex and cisplatinum. PMID- 11783260 TI - [Protective effect of Radix Salviae multiorrhizae on myocardial ischemia reperfusion injury]. PMID- 11783261 TI - [Influence of xiaoke granule on hemorrheology of mice with diabetes mellitus]. PMID- 11783262 TI - [Research on biotherapeuticeffect anticancerous remedies]. PMID- 11783263 TI - [On the role and significance of studies in exploring the material basis and therapeutical mechanism of composite recipe of Chinese herbal drugs]. PMID- 11783264 TI - [Study on relationship between insulin-resistance and syndrome differentiation typing in hypertensive patients]. AB - OBJECTIVE: To find the relationship between insulin-resistance and Syndrome Differentiation typing (SDT) in hypertensive patients. METHODS: Two hundred and nine patients of early stage hypertension with no complication of heart, brain or kidney were selected and classified into 4 types according to SDT, the Liver-Fire exuberant type (A), the Phlegm-Dampness abundant type (B), the Yin-Deficiency and Yang-Excess type (C) and the both Yin-Yang Deficiency type (D). Their insulin sensitivity were examined and compared with that of 40 healthy subjects. RESULTS: (1) Compared with healthy subjects, all hypertensive patients had apparent insulin resistance (P < 0.05). If the insulin sensitivity of healthy subjects was defined as 1, that of patients of type A, B, C and D were 0.54, 0.58, 0.65 and 0.80 respectively. (2) Comparison between the insulin sensitivity of type A, B and C showed no significant difference, while they were compared with type D, the difference was significant (P < 0.05), that is, the insulin sensitivity of type D was close to that of healthy subjects. (3) The fasting blood insulin of type D was obviously lower and the insulin sensitivity of type D was obviously higher than that of the other three types (P = 0.0001). (4) After adjusting age, sex and body mass indexes, multivariate regression analysis demonstrated that insulin sensitivity was closely correlated with SDT (P = 0.0001). CONCLUSION: Insulin resistance is one of the pathological basis for SDT in hypertension. PMID- 11783265 TI - [Clinical study on effect of scalp-acupuncture in treating acute cerebral hemorrhage]. AB - OBJECTIVE: To study the therapeutic effect of scalp-acupuncture in treating acute cerebral hemorrhage and its mechanism. METHODS: Sixty-four patients were divided into two groups, the acupuncture group and the control group. All were treated with mannitol and furosemide to reduce intracranial pressure, p-aminomethyl benzoic acid for hemostasis. The acupuncture group received scalp-acupuncture additionally. Neurofunction deficit scoring (NDS), hemorheology, thromboxane, prostacyclin, endothelin and transcranial Doppler (TCD) ultrasonic examination were taken before and after treatment. RESULTS: NDS of the acupuncture group was markedly better than that of the control group, especially in function recovering of limbs and speech. Blood viscosity, thromboxane and endothelin level of the acupuncture group lowered obviously, as compared with the control group, the difference was significant, P < 0.05. TCD showed that the cerebral blood flow was markedly improved in the acupuncture group. CONCLUSION: Scalp-acupuncture is safe and effective in treating acute cerebral hemorrhage, it is particularly effective in recovering limb paralysis and speech disturbance caused by cerebral hemorrhage. PMID- 11783266 TI - [Clinical observation on treatment of postcardiotomic complications with Chinese herbal medicine based on syndrome differentiation with angiocardiopathy]. AB - OBJECTIVE: To study the effect of Chinese herbal medicine (CHM) based on Syndrome Differentiation on postcardiotomic complications in patients with angiocardiopathy. METHODS: Aimed at the frequently encountered postcardiotomic complications including fever, cough and expectoration, belching, abdominal distension, palpitation, short breath, etc. CHM treatment was applied in combination with routine western drugs treatment (cardiac tonic, diuretics, vascular dilatator and anticoagulant). RESULTS: Twenty out of 22 patients with protracted fever and irresponsive to multi-antibiotics therapy were cured, the other one with hydrothorax received other therapy and the another one with drug fever was natural cured after stopping medication. Among 23 patients complicated mainly with respiratory symptoms, 17 were cured and 6 improved, among 15 with digestive symptoms, 12 cured and 3 improved, and among 7 with cardiovascular symptoms, 3 cured, 2 improved and 2 ineffective. CONCLUSION: CHM has good effect on postcardiotomic complications, it could improve the functional recovery of heart and lung. PMID- 11783268 TI - [Clinical study on acute upper respiratory tract infection treated with qingkailing injection]. AB - OBJECTIVE: To explore the effect of Qingkailing injection (QKLI) in treating acute fever. METHODS: Four hundred cases of acute upper respiratory tract infection were divided into three groups treated with QKLI 120 ml/d, 160 ml/d and 200 ml/d respectively, and compared with a control group treated with lincomycin 1.8 g/d. RESULTS: The markedly effective rate of QKLI was 84.14% which was better than that of lincomycin (75.83%). The mean initial time of QKLI (12.6 h) was shorter than that of lincomycin (17.6 h). Effect of QKLI on patients with disease course within one day was better than that within 3 days. No significant difference revealed between effects in groups treated with different dosage of QKLI. The effect of QKLI in lowering white blood cell count was similar to that of lincomycin. For patients with positive throat swab culture of pathogenic bacteria, QKLI displayed good antibacterial action in vivo. CONCLUSION: QKLI is a highly effective with rapid action drug for treatment of acute respiratory infection. PMID- 11783267 TI - [Effect of ginseng injection in treating congestive heart failure and its influence on thyroid hormones]. AB - OBJECTIVE: To observe the effect of Ginseng injection on congestive heart failure (CHF) and its influence on thyroid hormones. METHODS: Fifty-four Patients of CHF were divided into two groups. On the basis of conventional treatment of western medicine, the Ginseng injection was given to the treated group additionally. Blood level of triiodothyronine (T3), thyroxine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone (TSH) of all patients were determined before and after treatment by radioimmunoassay. RESULTS: There were significant difference between the treated group and the control group in cure rate and mean course of therapy. The levels of T3 and T4 of all patients were lower than those of the normal control before treatment, and rT3 were higher. Two weeks after treatment, T3 and T4 level in all patients increased significantly and rT3 level significantly decreased(P < 0.05, P < 0.01). CONCLUSION: Ginseng injection has a good effect on patients with CHF. It also has regulatory effect on thyroid hormones. PMID- 11783269 TI - [Study on prevention and treatment of middle and aged women diabetes with kidney deficiency and bone metabolic disturbance]. AB - OBJECTIVE: To Study the therapeutic effect of Chinese herbal medicine (CHM) for supplementing Qi, activating blood circulation and tonifying Kidney on prevention and treatment of middle and aged women diabetes with Kidney Deficiency and bone metabolic disturbance. METHODS: Clinical observation was taken in 52 patients, who were divided into two groups, the control group (treated with hypoglycemic agent alone) and the treated group (treated with hypoglycemic agent and CHM). RESULTS: Before treatment, patients of both groups showed obvious higher blood alkaline phosphatase, beta 2-microglobulin (beta 2-MG) level, urinary beta 2-MG, calcium and phosphorus level, but lower serum estradiol level than those in normal subjects. After 3 months' treatment, no apparent change on serum estradiol level was observed, but other parameters were all lowered obviously in the two groups, the changes revealed more obvious in the treated group. The symptoms of Kidney Deficiency, such as lumbodorsal pain, general fatigue, palpitation and vertigo, were improved after treatment, and the improvement was also more obvious in the treated group. CONCLUSION: CHM for supplementing Qi, activating blood circulation and tonifying Kidney was effective in improving Kidney Deficiency and mineral substance loss of bone in middle and aged women diabetes patients. The CHM and western drugs may acted synergistically. PMID- 11783270 TI - [Clinical study on retarding aging effect of tongbu recipe to traditional Chinese medicine]. AB - OBJECTIVE: To study the mechanism of Tongbu No. 1 (TB1, a prescription for reinforcing Kidney and Spleen, clearing up the bowel viscera to send Turbid downward and regulating Qi and blood) in retarding aging. METHODS: A controlled, multiple indexes study was conducted in 56 old subjects randomized into 3 groups. RESULTS: TB1 (containing ginseng leaf, cistanche, fleeceflower root, immature bitter orange, rhubarb, etc) could improve various symptoms of aging, and had the effect in regulating immune and endocrinal function, scavenging free radicals and adjusting coli flora. The effects of TB1 and TB2 (containing ginseng leaf, cistanche and fleeceflower root) were different significantly (P < 0.05, P < 0.01). CONCLUSION: TB1 has a good comprehensive effect in retarding aging. PMID- 11783271 TI - [Effect of total flavonoids of Astragalus on nitroxide in ischemia reperfusion injury]. AB - OBJECTIVE: To study the protective effect of total flavonoids of Astragalus (TFA) on ischemia/reperfusion injury. METHODS: Change of nitrite (NO2-), the terminal product of nitric oxide (NO) metabolism, and the effect of TFA and chloroquine (a phospholipase A2 inhibitor) on it were observed with hemorrhagic shock/reperfusion injury (S/R) rabbit model. RESULTS: Plasma NO2- content was positively correlated with blood pH and total carbon dioxide content lowering. TFA and chloroquine could block the decrease of NO in certain degree and might have some effect on maintaining acid-base balance of body. CONCLUSION: TFA has protective effect on ischemia/reperfusion injury. PMID- 11783272 TI - [Effect of baicalin and tetramethylpyrazine on intracranial hypertension of infectious brain edema in rabbits]. AB - OBJECTIVE: To evaluate the effects of mannitol (MN), baicalin (BC) and tetramethylpyrazine (TMPZ) on intracranial hypertension (ICH) of infectious brain edema induced by Pertussis bacilli (PB) in rabbits. METHODS: Forty-five rabbits were divided randomly into five groups: the normal saline group (A); the pertussis bacilli group (B); the MN treated group (C); the TMPZ treated group (D) and the BC treated group (E). PB was injected into the left internal carotid artery of rabbits to establish the infectious brain edema model, their intracranial pressure (ICP) was monitored continuously by fiberoptic ICP monitor. Treatments were given intravenously 1 hour after injecting PB, and changes of ICP, brain water content (WC), Evans blue (EB), Na+, K+ and morphology were observed within 4 hours after PB or NS injection. RESULTS: MN, TMPZ and BC all could reduce the brain edema and ICH in rabbits induced by PB, the effect of MN was the most rapid and obvious one, but it lasted for rather shorter time, while the effect of TMPZ and BC was initiated later but lasted for a longer time. The ICP of Group C in 2nd to 4th hour was higher than that of Group D and Group E, but lower than that of Group B. The ICP of Group E in 3rd to 4th hour was lower than that of group D. At the same time of lowering ICP, brain WC, EB, Na+ contents and pathologic morphologic change were also alleviated. CONCLUSION: Both BC and TMPZ could reduce ICP in infectious brain edema, the effect of BC was better than that of TMPZ. PMID- 11783273 TI - [Effect of Panax notoginseng saponin on Ca2+, CaM in craniocerebral injury]. AB - OBJECTIVE: To explore the change of nerve cell Ca(2+)-overload, Ca(2+)-CaM and the effect of Panax Notoginseng saponin (PNS) on it in craniocerebral injury. METHODS: Blood and brain contents of Ca2+, CaM were examined by radio-immunoassay (RIA) and atomic absorption spectrometry(AAS), and effect of PNS on these parameters was observed in craniocerebral injury rabbits. RESULTS: The levels of Ca2+ and CaM in blood and those in brain were significantly positively correlated. PNS could reduce Ca2+ and CaM contents in blood and in cerebral tissue. CONCLUSION: PNS could block the Ca(2+)-overload and Ca(2+)-CaM complex production in nerve cell after cranial cerebral injury, thereby to protect the injured brain in a certain degree. Blood CaM level is an objective index for assessment of Ca(2+)-overload in nerve cell. PMID- 11783275 TI - [On the integration of functional and morphologic syndrome differentiation]. PMID- 11783274 TI - [On three necessities in the procedure of preparation of new Chinese herbal drugs]. PMID- 11783276 TI - [Prevention and treatment of pulmonary hypertension with Radix Salviae multiorrhiazae]. PMID- 11783277 TI - [Research on prematurity in childhood]. PMID- 11783278 TI - [Clinical and experimental study on zhixie buye mixture in treating infantile diarrhea complicated with dehydration]. AB - OBJECTIVE: To observe the therapeutic effect of Zhixie Buye mixture (ZXBYM) on infantile diarrhea patient with mild and middle degree of dehydration. METHODS: The controlled observation method was adopted in the clinical and experimental study. RESULTS: There was no significant difference in the treatment of dehydration between the ZXBYM group and ORS group (P > 0.05), while it was more effective for ZXBYM to eliminate the symptoms such as vomiting and abdominal distension (P < 0.01). In addition, it was confirmed that the ion concentration of sodium, potassium, chlorine, glucose and osmotic pressure in the mixture was similar to those in ORS. Animal experiment showed that it has the effect of rat intestine peristalsis suppression and water absorption promotion in colon for ZXBYM. And there was statistical difference in antidiarrhea effect between the mixture and ORS (P < 0.01). CONCLUSION: The ZXBYM is an effective mixture in the treatment of diarrhea with dehydration. It has a good prospect of development and application. PMID- 11783279 TI - [Clinical study of treating infantile acute nephritis with antipyretic and detoxication, cooling blood and diuretic principle]. AB - OBJECTIVE: To find out the relationship between nitric oxide and onset of infantile acute nephritis, and the effect of traditional Chinese medicine (TCM) and Western medicine (WM) combination therapy. METHODS: Dividing 44 infantile acute nephritis patients into two groups. Group 1 was treated with cooling blood and diuretic principle, together with WM, Group 2 was treated with antipyretic and detoxication, cooling blood and diuretic principle, together with WM. The content of nitrite/nitrate iron (Fe NO2/NO3) in blood before and after treatment were determined through Griess nitrate reduction method, then compared with that of 28 healthy children. RESULTS: The content of Fe NO2/NO3 being in acute nephritis period was obvious higher than that of control group and reconvalecent period, P < 0.01. The macroscopic hematuria was higher than that of microscopic hematuria, P < 0.01. Urinary alexin third element (C3) and alpha 2-macroglobulin (alpha 2-M) positive patients Fe NO2/NO3 was higher than that of negative ones, P < 0.01. Those complicated with infection Fe NO2/NO3 was higher than that without infection P < 0.01. Short term cure rate of group 2 was higher than that of group 1, P < 0.05. Nitric oxide may participate the onset and pathogenesis of infantile acute nephritis. CONCLUSION: TCM-WM combination therapy, especially antipyretic and detoxication, cooling blood and diuretic principle, could restrain nitric oxide from damaging tissue and remitting disease. PMID- 11783280 TI - [Clinical study on hyperthyroidism of yang hyperactivity type due to yin deficiency treated by jiakang ning capsule]. AB - OBJECTIVE: To investigate the effect of Jiakang Ning (JKN) capsule on hyperthyroidism. METHODS: Eighty-five cases of hyperthyroidism were divided into JKN group (24 cases), JKN with low dose Tapazol group (35 cases) and Tapazol control group (26 cases) at random. The effects were evaluated by total effective rate, using principal symptoms, body weight, EKG, thyroid hormone and atrial natriuretic peptide (ANP) after 6 months. RESULTS: The total effective rates of three groups were 83.8%, 97.1%, 88.5% respectively, and there were insignificant difference among them statistically (P > 0.05). The first two groups had better effect in principal symptoms than Tapazol control group (P < 0.05). There were similar results in adjusting thyroid dysfunction and abnormal EKG, decreasing ANP and increasing body weight among those three groups (P > 0.05). CONCLUSION: The effect on hyperthyroidism treatment by JKN capsule was satisfactory. The combination of Chinese herbs with western medicine could enhance the curative effect of hyperthyroidism without obvious side-effects. PMID- 11783281 TI - [Clinical observation on treatment of bile regurgitational gastritis with danwei capsule]. AB - OBJECTIVE: To evaluate the therpeutic effect of Danwei capsule in treating bile regurgitational gastritis. METHODS: One hundred and thirty-four patients with bile regurgitational gastritis were divided into two groups. Danwei capsule was used in therapeutic group and Motilium was used in control group. RESULTS: The total effective rate in therapeutic group was 92.59%, and 71.70% in control group (P < 0.01). The improvement in symptoms, physical findings and bile regurgitation in therapeutic group was better than that of control. CONCLUSION: Curative effect of Danwei capsule was better than that of Motilium, which should be used widely. PMID- 11783282 TI - [Study on effect and mechanism of essential garlic oil in inhibiting monocyte vascular endothelial cell adhesion induced by interleukin-1 alpha]. AB - OBJECTIVE: To observe the effects of essential garlic oil (EGO) on vascular cell adhesive molecule-1 (VCAM-1) expression of endothelial cell and monocyte adhesion induced by interleukin-1 alpha (IL-1 alpha). METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated by pancreatin digestion method and co cultured with U937 monocyte and IL-1 alpha or EGO + IL-1 alpha respectively. The adhesion rate of monocyte to endothelial cell was measured and mean fluorescent intensity of immuno-stained of VCAM-1 was determined by ACAS 570. RESULTS: EGO showed significant inhibition on VCAM-1 expression induced by IL-1 alpha either in simple culture with HUVEC or in co-culture with HUVEC + U937, and could obviously down regulate the monocyte-endothelial cell adhesion under effect of IL 1 alpha. CONCLUSION: EGO has the effect of antagonizing against adhesion of monocyte and vascular endothelial cell, it may be due to the inhibition of EGO on adhesive molecular expression on endothelial cell. PMID- 11783283 TI - [Exploring into relationship between serum lipoprotein electrophoretogram and the differentiation as phlegm stasis syndrome of aged coronary heart disease patients]. AB - OBJECTIVE: To observe the relationship between dynamic balance of the disturbance of serum lipoprotein and the 5 syndrome-types during Phlegm stasis syndrome (PSS) differentiation. METHODS: There were 171 patients, among them 81 cases were performed coronary arteriography (CAG). The serum lipoprotein electrophoretogram (SLPG) was examined by the double gradient polyacrylamide gel electrophoresis and the serum total cholesterol (TC) was determined with enzymatic method. RESULTS: (1) Comparing the PSS with the control group, there was significant difference in the abnormal items (P < 0.05-0.01). The blood stasis syndrome, PSS, and the Qi stagnation blood stasis syndrome were more than the phlegm syndrome and the non PSS ones. The abnormal index of SLP (SLPI) had the following order: PSS(SLPI 1.941) > Qi stagnation blood stasis syndrome (1.901) > blood stasis syndrome (1.643) > phlegm syndrome (1.357) > non-PSS(1.105) and > the control syndrome (0.056). (2) The positive cases in CAG was 64 patients, in SLPG, it was 59 cases (92.19%). The negative in CAG was 17 cases, but the positive in SLPG, it was 14 cases (82.35%). (3) As the PSS developed further, the TC had an increasing tendency, but their average was less than 2100 mg/L, under the critical level. CONCLUSION: As the risk factor of the aged CHD, the TC was not an ideal criteria, the SPLG was an effective index. It was related with the PSS differentiation of the aged CHD. PMID- 11783285 TI - [Analysis in pulmonary ventilatory function from 100 patients with ano-rectal diseases caused by deficiency of qi]. AB - OBJECTIVE: To explore the pathogenesis of ano-rectal diseases caused by deficiency of Qi, which is correlated with obstruction of pulmonary ventilation. METHODS: The pulmonary ventilatory function was measured in 100 patients with the internal piles, the interno-external hemorrhoid and prolapse of rectum, the prolapse of anus was the principal symptom of them. RESULTS: Data from the 100 patients showed that 67% of them were diagnosed with the obstruction of pulmonary ventilation, the ratio was far less in the health control group. FEV 1.0 (mean +/ s) (2011.65 +/- 875) ml, MMF (1.84 +/- 1.24) L/s and PEF (2.34 +/- 1.51) L/s in male patients, (1551.54 +/- 514) ml, (1.57 +/- 0.62) L/s and (1.85 +/- 0.92) L/s in female patients, but those values were higher in the control than in the patients. The statistical analysis was performed and the difference was significant between patients and the control group (P < 0.01). CONCLUSION: The patients with ano-rectal diseases caused by deficiency of Qi accompanied with obstruction of pulmonary ventilation in different degree and varied sorts, it confirmed that the pathogenesis of ano-rectal diseases caused by deficiency of Qi is related with "sinking of pectoral Qi". PMID- 11783284 TI - [Clinical and experimental study on the treatment of endometriosis with dan'e mixture]. AB - OBJECTIVE: To find a medicine to treat endometriosis effectively with less side effect. METHODS: Dan'e mixture (DEM, consists of Radix Salviae Miltiorrhizae and Rhizoma Zedoariae) was used to treat 189 cases of endometriosis and the change of symptom and sign, the B ultrasonograph, the anti-endometrium antibody and endometriosis quantitative diagnostic index were observed, another 160 cases were treated with Danazol as control, also using animal model to treat with DEM and Danazol. RESULTS: One hundred and eighty-nine cases were treated for 9 months. According to National Standards, 39 cases (20.6%) were cured, 67 cases (35.4%) were markedly effective, 67 cases (35.4%) were effective, and 16 cases (8.4%) were ineffective. Compared with 160 cases treated with Danazol for 9 months, the total effective rates were 95% and 91.5% respectively, the difference between them was insignificant. Animal experiments showed the similar results to the clinical ones. CONCLUSION: SZM is a safe and effective medicine to treat endometriosis, which deserves further study and development. It is particularly helpful for diagnosis, treatment and prevention of endometriosis in the early stage. PMID- 11783286 TI - [Effect of three composite recipes on content of monoamine transmitters in hypothalamus induced by intracerebroventricular injection of interleukin-1 of rats]. AB - OBJECTIVE: To explore the different effects of Youguiyin decoction, Sijunzi decoction, Taohong Siwu decoction on the content of monoamine transmitters in the hypothalamus induced by cytokines. METHODS: A reactive status of hypothalamic monoamine transmitters to cytokine in rat was built by observing the content change of monoamine transmitters in hypothalamic homogenate after intracerebroventricular (icv) injection of human recombinant interleukin-1 beta(IL-1 beta). On this basis, the different effect of three composite recipes on this status was observed. RESULTS: The content of norepinephrine (NE) declined significantly compared with control group after icv injection of IL-1. Compared with IL-1 group, Youguiyin further reduced the content of NE induced by icv injection of IL-1, while Taohong Siwu decoction and Sijunzi decoction did not show any effect on this status. CONCLUSIONS: It seems that Youguiyin for tonifying Kidney could increase the reactivity of hypothalamic NE neuron, Sijunzi decoction for invigorating Spleen and Taohong Siwu decoction for promoting blood circulation did not show this effect. PMID- 11783287 TI - [Effect of tongbiling on synoviocyte function in adjuvant arthritis rats]. AB - OBJECTIVE: To study the effect of Tongbiling (TBL) on the proliferation of synovial fibroblast and interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha) and postaglandin E2(PGE2) secretion by synoviocytes in adjuvant arthritis (AA) rats. METHODS: Synovial fibroblasts was derived from culture of tissue piece. The effect of primary synoviocyte culture supernatants on the fibroblast proliferation were assayed and IL-1, TNF-alpha bioactivity and PGE2 content of supernatants of cultured synoviocytes were measured. RESULTS: TBL could inhibit significantly the synovial fibroblast proliferation (P < 0.001), and down regulated IL-1, TNF-alpha and PGE2 productions (P < 0.01); indomethacin could promote obviously the synovial fibroblast proliferation (P < 0.001). It inhibited significantly PGE2 production, but further up-regulated the IL-1 and TNF-alpha secretion by synoviocytes (P < 0.01). CONCLUSION: The therapeutical effect of TBL on AA might be associated with its down-regulating the secretory function of synoviocyte, then restoring the abnormal proliferation of fibroblast to normal levels. PMID- 11783288 TI - [Experimental study on effect of yishen shengxue tablet in treating aplastic anemia]. AB - OBJECTIVE: To study the mechanism of Yishen Shengxue Tablet (YSSXT) in treating aplastic anemia. METHODS: Observing the effect of YSSXT on hematopoietic, immunologic, anti-infection and body resistance of model mice of aplastic anemia. RESULTS: YSSXT had marked effect of promotion on recovering myleran injury induced reduction of colony forming unit-spleen (CFU-S), colony forming unit culture (CFU-C), colony forming unit-erythrocyte (CFU-E), markedly promoting the peritoneal macrophage phagocytosis of normal mice, also markedly lower the mortality of Staphylococcus aureus inoculated mice, and elevate the anoxia resistant ability under normal pressure of anoxic mice, prolonging their survival time. CONCLUSION: Using YSSXT to treat aplastic anemia that the effectiveness might be realized through promoting the proliferation of hematopoietic stem cells of bone marrow, enhancing the non-specific immunity, and the anti-infection as well as body resistance. PMID- 11783289 TI - [Exploring the complements of traditional Chinese medicine]. PMID- 11783290 TI - [Progress of clinical basic study of acupuncture in the treatment of gastrointestinal diseases]. PMID- 11783291 TI - [Effect of composite blood-activating decoction on expression of adherent molecule and cyclin in bone marrow hematopoietic cells in mice of immune-induced aplastic anemia]. AB - OBJECTIVE: To study the effect of composite blood-activating decoction (CBAD) on expression of adherent molecule CD49 d and cyclin D2 in bone marrow hematopoietic cells in experimental immune-mediated aplastic anemia (AA) mice. METHODS: After the model of AA was established, the animals were fed with 0.2 ml of 100% CBAD, twice a day for 12 days. Te CD49 d and cyclin D2 expression level of bone marrow hematopoietic cells in model mice were measured by flow cytometor analysis system at the 13th day of experiment. RESULTS: CD49 d expression level in CBAD group was significantly higher than that in the AA group (P < 0.05), and was similar to that in the normal group (P > 0.05). The expression of cyclin D2 in CBAD group was significantly higher than that in the AA group (P < 0.01), but the cell count of G0 + G1 phase was significantly lower in the CBAD group, as compared with the AA group, P < 0.01. CONCLUSION: CBAD can increase the expression of adherent molecule CD49 d and cyclin D2 in bone marrow hematopoietic cells, and promote the growth of hematopoietic cells. PMID- 11783292 TI - [Influence of blood-activating drugs on adhesion and invasion of cells in lung cancer patients]. AB - OBJECTIVE: To investigate the influence of some blood-activating drugs like Tetramethylpyrazine, Tanshinone II A, Hirudin and thrombin on adhesive and invasive behavior of PGCL3 and PAa cell lines. METHODS: Using the above-mentioned blood-activating drugs in various concentration to treat PGCL3 and PAa cells, and the changes in adhesion to fibronectin and invasion in Boyden Chamber of these cells, alone or after interacted with human platelets, were observed. RESULTS: Tetramethylpyrazine, Hirudin and thrombin could increase the adhesion of cells to fibronectin and Tanshinone II A decrease it. Tetramethylpyrazine, Tanshinone II A and Hirudin inhibited the invasion of PGCL3 cells in Boyden Chamber, and thrombin augmented the process. CONCLUSION: The blood-activating drugs may either inhibit or promote the invasion and metastasis of PGCL3 and PAa cells in the light of various conditions. PMID- 11783293 TI - [Biomechanical experimental study on effective fraction of radix salviae miltiorrhizae on healing of bone fracture]. AB - OBJECTIVE: To assess the effect of Danshen-9403 (DS-9403, an effective fraction of Radix Salviae Miltiorrhizae) on healing of bone fracture. METHODS: Standardized radial fracture was performed in 120 Wistar rats. The model animals were randomized into four groups: group A was fed with DS-9403, group B injected with Staphylococcus Aureus, group C with normal saline, and group D with Salviae injection. The treatment began at the first day of fracture. The rats were sacrificed on the 25th, 39th and 50th day separately in batches and their intact radii were removed by dissection for detecting load and stress of three-point bending test with autograph universal material testing machine (Shimazu, Japan). RESULTS: The parameters of load in DS-9403 treated groups on the 39th day and that of stress at 25th, 39th and 50th day were (6.20 +/- 1.32) N, (5.71 +/- 3.58) N/mm2, (8.27 +/- 2.42) N/mm2 and (66.25 +/- 26.21) N/mm2 respectively, which were significantly higher than those in other groups, P < 0.05. CONCLUSION: DS-9403 has the action of increasing the strength of fracture healing site. PMID- 11783295 TI - [Relation between modernization of traditional Chinese medicine and syndrome differentiation of integrated traditional Chinese and Western medicine]. PMID- 11783294 TI - [The ideal index on quality control of new ingredients in compound medicine]. PMID- 11783296 TI - [Effect of Chinese herbal medicine on immuno-inhibition caused by chemotherapy and radiotherapy]. PMID- 11783297 TI - [Comparative study on therapeutic effects of gandou tablet I and dimercaptosuccinate acid in treating Wilson disease]. AB - OBJECTIVE: To compare the effects of Gandou I (GD, a Chinese herbal preparation) and dimercaptosuccinate acid (DMSA) in treating Wilson disease (WD). METHODS: Ninety-four patients with WD were divided into 2 groups, 32 cases in the GD group and 62 in the DMSA group, they were treated with GD and DMSA respectively. The therapeutic course was 4 weeks for both groups. Modified Goldstein's Degree was adopted to evaluate the clinical effect. RESULTS: The total effective rate of the GD group was 71.9%, which was similar to that of the DMSA group (77.4%, P > 0.05). But the adverse reaction occurred in the latter group was more than that in the former. CONCLUSION: GD is a low toxic and highly effective drug for long term treatment of WD. PMID- 11783298 TI - [Direct determination of serum content of ferulic acid treated with boiling water in HPLC in volunteers after oral Administration of Coronary Heart No. II decoction]. AB - OBJECTIVE: To develop a new method for clinical pharmacokinetic detection of chemical component of Coronary Heart NO. II in serum after oral administration in healthy person. METHODS: Content of ferulic acid (FA) in serum, which had been treated with boiling water bath, was determined directly by high performance liquid chromotography (HPLC) and spectrophotometer. After qualitative detection performed by using Bi- and tri-dimensional HPLC and ultraviolet spectrophotometer, the quantitative detection was determined with the internal standard (coumarin). RESULTS: When eluted by mobile phase of a mixture of methanol, acetic acid and water (38:0.3:61.7 in ratio), and stationary phase of C18(ODS2), column (150 mm x 4.6 mm, 5 microns), the minimal detectable limit of free methanol FA was 6 ng (N/S = 3), and the minimal detectable serum FA concentration, after 10 min of boiling water bath, was 20.2 micrograms/L, with a linearity of 33.7-2156.8 micrograms/L, r = 0.9993. The mean recovery of serum FA was (93.59 +/- 2.36) micrograms/L. The RSD within day and day-to-day were all less than 8.44%. CONCLUSION: In comparing with sample Preparation of acetonitrile, this method is simple, rapid, sensitive, cheap, accurate, specific, reproducible and no toxic. PMID- 11783299 TI - [Observation of preventing and treating effect of Salvia miltiorrhiza composita on patients with ischemic coronary heart disease undergoing non-heart surgery]. AB - OBJECTIVE: To observe the preventing and treating effect of Salvia miltiorrhiza composita (SMC) on patients with ischemic coronary heart disease (CHD) undergoing non-heart surgery. METHODS: The 108 patients were randomly divided into the control group and treatment group. In the treatment group, each patient of 54 were administered SMC intravenously during the operation. ECG, HR, MAP and SpO2 were observed and bleeding quantity was measured perioperatively. RESULTS: Effective rate of ECG in treatment group was 90.7% (49/54 cases) and the control group was 35.2% (19/54 cases). There was significant difference between the two groups (P < 0.01). HR of the treatment group was no great flutter but control group became faster (P < 0.05). MAP and SpO2 of the two groups were no significant difference perioperatively. There was no significant difference to bleeding quantity between the two groups. CONCLUSIONS: SMC could effectively improve and protect myocardial ischemia in patients with CHD undergoing non-heart surgery, and no side effect was found. PMID- 11783300 TI - [Clinical observation of side effects of Tripterygium preparation]. AB - OBJECTIVE: To observe the side effects of Tripterygium preparation (TP) in the course of treatment. METHODS: Two hundred and seventy-one cases of patients with rheumatoid arthritis (RA) were treated using various TP to observe the occurrence of adverse reaction. RESULTS: The influence on reproductive system with TP extracted from the leaf ester tab were less than that from the root (TP tab and TP multiglycoside tab, TPMG). In group of TPMG the rate of side effect of 60 mg daily dosage was more than 30 mg daily (P < 0.01). The main influence on digestive tract and irregular menstruation was before age of 50 years and on renal function was after age of 50 years. Those adverse reactions mainly occur within first ten years in long therapy period. The side effects of TPMG produced in the Dampness-Heat type of RA were lower than Yin-Deficiency of Liver and Kidney type of RA (P < 0.05). CONCLUSION: TP ester tab is available for young woman and TPMG tab is suitable for the Dampness-Heat type of RA with lower dosis maintenance therapy. PMID- 11783301 TI - [Clinical and experimental study on effect of Shuguan granule on mid-late rheumatoid arthritis]. AB - OBJECTIVE: To explore the therapeutic mechanism of Shuguan Granule (SGG) in treating mid-late rheumatoid arthritis. METHODS: Based on the principle of reinforcing Kidney to treat arthritis, removing phlegm to remove stasis, two SGG, Shuguan Wenjing granule (SW) and Shuguan Qingluo granule (SQ) were prepared and used to treat mid-late 44 and 43 patients of rheumatoid arthritis respectively. The clinical result was compared with that of Wangbi Granule. Animal experiments on the effect of the two SGG were conducted. RESULTS: The total effective rate of the SW, SQ and control group was 88.64%, 93.02% and 73.17% respectively. Results of experimental studies in rats with adjuvant-induced arthritis showed that the two SGG obviously raise the level of serum SOD, and lowered the levels of serum interleukin-1, plasma prostaglandin E2 and thromboxane B2, as compared with the model group, the difference was significant (P < 0.05, P < 0.01). CONCLUSION: The two SGG have a comprehensive function of anti-inflammatory, analgesia, antioxidation, antihypercoagulation and immunoregulation. PMID- 11783302 TI - [Study on relationship between Deficiency Syndrome of TCM and the biological behavior in patients of esophageal carcinoma]. AB - OBJECTIVE: To investigate the relation between Deficiency Syndrome (DS) of TCM and the invading depth, lymphnode metastasis, TNM stage and prognosis prediction of esophageal carcinoma. METHODS: According to Syndrome Differentiation of TCM, 101 patients of esophageal carcinoma were evaluated before operation and divided into two groups, the DS group and the non-DS group. RESULTS: Thirty-eight cases in the 101 patients were DS, among them, 14 were Qi-Deficiency, 10 Yin Deficiency, 10 Qi-Yin Deficiency, 2 Qi- and blood Deficiency, 1 Yang-Deficiency and 1 Yin-Yang Deficiency. There were significant differences between the DS group and non-DS group in the invading depth (deeper in DS), metastasis of lymphnode (severer in DS) and TNM stage (later in DS) of esphageal carcinoma, (P < 0.05). CONCLUSION: There is a significant relation between DS and the biological behavior of esophageal carcinoma. The prognosis of DS patients is poorer than that of the non-DS patients. PMID- 11783303 TI - [Effect of TCM on plasma beta-endorphin and placental endocrine in threatened abortion]. AB - OBJECTIVE: To explore the effect of TCM on plasma beta-endorphin (beta-EP) and placental endocrine function in patients of threatened abortions (TA). METHODS: Changes of plasma beta-EP, gonadotrophin releasing hormone (GnRH), human chorionic gonadotrophin (HCG), progesterone (P4) levels were measured with RIA in 40 cases of TA with a history of recurrent spontaneous abortion treated with Chinese herbal medicine for reinforcing Kidney and Qi, hemostasis and antiabortion. And the results were compared with those of normal early pregnant women and patients with incomplete abortion as control. RESULTS: The plasma beta EP level in TA was significantly higher than that in normal pregnant women, P < 0.01. On the contrary, plasma GnRH, HCG and P4 were obviously lower in TA as compared with those of the normal cases, P < 0.01. After treatment, 36 of the 40 patients succeeded in the continuity of pregnancy, their symptoms of TA disappeared, and the above-mentioned four criteria measured at 10-12th week of gestation were similar to those of normal cases, P > 0.05. CONCLUSION: TCM treatment can regulate plasma beta-EP and placental endocrine function in threatened abortion. PMID- 11783304 TI - [Clinical and experimental study of yushen jiangtang tablet in treating non insulin dependent diabetes mellitus]. AB - OBJECTIVE: To evaluate the therapeutic effect and safety of Yushen Jiangtang Tablet (YSJTT) in treating non-insulin dependent diabetes mellitus (NIDDM) of Qi Yin Deficiency Syndrome (QYD). METHODS: One hundred and one patients of NIDDM with QYD were treated with YSJTT and compared with 60 patients of the control group treated with Shenqi Jiangtang Tablet. The experimental study on pharmacologic effect and toxicity of YSJTT was also conducted. RESULTS: The total effective rate of the YSJTT group was 87.12% and the markedly effective rate 44.55%, while those of the control group were 70.00% and 18.33% respectively, comparison between the two groups showed that the effect of the YSJTT group was superior to that of the control group, P < 0.01. No acute or chronic toxic or side effect was found in animal experiment. Pharmacologic study showed that YSJTT had obvious effect in decreasing blood glucose and serum triglyceride levels in rats with alloxan induced diabetes. CONCLUSION: YSJTT is effective in treating NIDDM, and apparent toxic-side effect of it was not found. PMID- 11783305 TI - [Clinical and experimental study on treatment of asthma with juanxiao tablet]. AB - OBJECTIVE: To evaluate the therapeutic effect of Juanxiao Tablet (JXT) in treating asthma. METHODS: Clinical observation on 447 cases of asthma was done by double- or single-blind control method, and the therapeutic effect and safety of JXT were analysed. The effect of JXT in antiasthma, expectorant, antisepsis, hypoxia tolerance was studied, and its acute and chronic toxicity also examined. RESULTS: The clinical control rate in patients treated with JXT was 38.2%, its markedly effective rate 31.2% and total effective rate 93.4%, while in patients treated with Oleum Vitex Negundo, the respective data were 13.3%, 20.0% and 68.5%. Results of pulmonary function and IgE measurement were consistent with clinical effect. Experimental study showed that the JXT has the action of anti asthma, expectorant, antisepsis and hypoxia tolerance enhancement, its LD50 was (40.48 +/- 5.17) g/kg. CONCLUSION: JXT is a new Chinese herbal preparation of good effect, less toxic-side reaction for asthma treatment. PMID- 11783306 TI - [Experimental study of influence of yiqi huoxue serial recipes on basement membrane in membranous nephritis in rabbits]. AB - OBJECTIVE: To clucidate the mechanism of the therapeutic effect of Yiqi Huoxue (YQHX) serial recipes on membranous nephritis. METHODS: Forty-nine New Zealand male rabbits were made to menbranous nephritis model by cation bovine serum albumin and divided into 5 groups, the group A (treated by Qingre Moshen granule), B (treated by Bushen Moshen granule), C (treated by steroid), D (the control group) and E (the normal group). Twenty-four hours' urinary protein content of the animals was determined every week, and plasma albumin, blood lipid, renal function and prostaglandins were tested by the end of experiment. And pathological changes of basement membrane were observed by using light, electronic and immunofluorescent microscopy with polyethylene imine stain. RESULTS: The 24 hours urinary protein content, plasma albumin and blood lipid in the group A and B were lower than those in the control group significantly, P < 0.01 or 0.05, while those in the group C and the D were similar, P > 0.05. In comparing the group A and B with the group C, the difference was also significant, P < 0.05. Light, electronic and immunofluorescent microscopic examination all showed that the pathologic changes in the group A, B and C were lesser than that of the control, the effect was in the order A > B > C. CONCLUSION: YQHX serial recipes can reduce urinary protein content, elevate plasma albumin level, restore the charge barrier effect of and attenuate the immune complex deposition on the basement membrane of glomeruli. PMID- 11783307 TI - [Clinical observation of tiaojining recipe in combination with corticosterone in infantile primary nephrotic syndrome]. AB - OBJECTIVE: To investigate the effects of Tiaojining recipe (TJNR) combined with corticosterone (CS) in treating infantile primary nephrotic syndrome (IPNS). METHODS: Sixty inpatients with IPNS were divided into two groups, which consisted of 30 cases as the treated group treated by TJNR combined with CS and 30 cases of the control group were treated by CS alone for 8 weeks. The changes of urinary protein, serum albumin, blood cholesterol, platelet and blood pressure before and after treatment were observed. RESULTS: The total effective rate of the treated group was significantly higher than that of the control group (P < 0.01). The times for urinary protein disappearance of the treated group was significantly shorter than that of the control group (P < 0.05). Compared with the control group. TINR could prevent hypertension, lower lipidemia and platelets (P < 0.01). CONCLUSION: TJNR could enhance the curative effects of CS on IPNS and reduce the side-effects of CS safely and effectively. PMID- 11783308 TI - [Effect of emodin on human kidney fibroblast proliferation]. AB - OBJECTIVE: To study the effect of emodin on proliferation of human kidney fibroblasts in vitro. METHODS: After human kidney fibroblasts were cultured, isolated and identified, both the effects of five different concentrations of emodin (10, 30, 50, 80 and 100 micrograms/ml) on 3H-TdR incorporation, and the effects of three different concentrations of emodin (10, 50 and 100 micrograms/ml) on cell cycle by flow cytometry were investigated. RESULTS: The exposure of human kidney fibroblasts to emodin (10-100 micrograms/ml) caused a dose-dependent reduction in 3H-TdR (r = 0.995, P < 0.01), and could delay the progress of human kidney fibroblasts from G1 to S phase. CONCLUSIONS: Emodin inhibited the proliferation of human kidney's fibroblasts by inhibiting the cell DNA synthase and delaying the progress of cell cycle. These findings might provide part of experimental basis for the clinical use of emodin. PMID- 11783309 TI - [Investigation of urinary interleukin-6 level in chronic renal failure patients and the influence of Rheum palmatum in treating it]. AB - OBJECTIVE: To assess the clinical significance of urinary interleukin-6 (IL-6) level in chronic renal failure (CRF) patients and the effect of Rheum palmatum (RP) in treating it. METHODS: RP and captopril were given to the study group, while captopril was given to the control group alone, and level of urinary IL-6 was determined by sandwich-ELISA. RESULTS: Urinary IL-6 level in CRF patients was obviously higher, than that in healthy control (P < 0.01). After treatment, the urinary IL-6 and serum creatinine reduced significantly in the study group (P < 0.05), and there was significant difference compared with that in the control group (P < 0.05). CONCLUSIONS: Determination of urinary IL-6 level is useful in studying the severity of immune inflammation of CRF. RP improves renal function by inhibiting the production of IL-6 and lowering immune inflammation. PMID- 11783310 TI - [Clinical study on the expression level of lymphocyte function-related antigen of breast cancer patients]. AB - OBJECTIVE: To explore the protein expression level of the lymphocyte function related antigen CD11a, CD18, CD54 of breast cancer patients' blood, cancer tissue and drainage lymph node, and the effect of chemotherapy as well as Yiqi Yangxue Granule on its expression level. METHODS: The immunohistochemical assay and flow cytometry were used to determine the change of the protein expression level of CD11a, CD18, CD54 on the lymphocyte of blood, cancer tissue and lymph node between before and after chemotherapy and chemotherapy plus Yiqi Yangxue Granule in 72 patients suffering from breast cancer. RESULTS: In breast cancer patients, the level of CD54 was increased more obviously than that of control group, the CD11a, CD18, CD54 of lymphocytes in cancer tissue increased remarkably, while the CD54 expression positive rate reached 100%, the expression level of CD11a, CD18, CD54 which increased significantly in negative lymph node obviously higher than that of positive lymph node. CONCLUSION: The level of adherence cell was markedly abnormal in breast cancer patients, whose immune adherence function disturbed. Although chemotherapy kills the tumor cells, it damages the immune adherence function, Yiqi Yangxue Granule could improve the immune function and enhance the anti-cancer effect of patients. PMID- 11783311 TI - [Improvement and application of multi-infarct dementia model in rats]. AB - OBJECTIVE: To improve the method of inducing the multi-infarct dementia (MID) model in rats to observe the pharmacodynamic effect of Jiannao Yizhi (JNYZ) granule on MID. METHODS: Retrograde injection with the homologous embolus through the external carotid artery initiated the multi-infarct dementia in rats. The experiment of behavior and morphology were conducted. RESULTS: The extensive and multiple foci of infarction and the obviously declining ability of learning and memory were observed in the model group; the action of JNYZ granule and hydergine could obviously improve them. CONCLUSION: This model is useful to carry out basic research and screen new drugs in treating MID. PMID- 11783312 TI - [Effects of xiaopi yishen oral liquid on hypothalamus-pituitary-adrenal gland thymus axis in stressed rats]. AB - OBJECTIVE: To investigate the effect of Xiaopi Yishen (XPYS) oral liquid on the rats under repeated forced cold water swimming (RFCWS) stress. METHODS: The changes of serum monoamine, ascorbic acid levels in adrenal gland, monoamine levels in hypothalamus and hypophysis, and thymus index were determined. RESULTS: XPYS lowered the increasing of serum DA, 5-HT, improved the reducing of ascorbic acid in adrenal gland and NE, HVA, 5-HT, 5-HITT in hypothalamus and hypophysis of RFCWS-stressed rats. CONCLUSION: The mechanism of XPYS is in connection with the regulation of hypothalamus-pituitary-adrenal gland-thymus axis. PMID- 11783313 TI - [Protective effects of tongli gongxia herbs on gut barrier in rat with multiple organ dysfunction syndrome]. AB - OBJECTIVE: To explore the protective effects of Tongli Gongxia (TLGX) herbs on gut barrier with multiple organ dysfunction syndrome (MODS). METHODS: The MODS models were induced by intraperitoneal injection of Zymosan A, and Dachengqi decoction (DCQD) was used in treating MODS models. The levels of endotoxin in the peripheral and portal blood, and the contents of diamine oxidase (DAO), xanthine oxidase (XOD), malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor (TNF), the permeability of intestinal mucosa and enterocytes, and the histopathologic changes were observed. RESULTS: The gut barrier function in MODS rats were severely damaged. DCQD could significantly reduce the levels of endotoxin in the blood (P < 0.01), the contents of XOD, MDA and TNF in the blood and intestinal tissue were lowered (P < 0.01), but the levels of GSH in blood and intestinal tissue were raised (P < 0.05). Levels of DAO in the intestinal tissue was markedly increased (P < 0.01). DCQD could reduce the permeability of intestinal mucosa and enterocytes, and attenuate the histopathologic changes of intestinal mucosa in MODS rats. CONCLUSION: TLGX herbs have apparently protective effects on the gut barrier in MODS rats. PMID- 11783314 TI - [Effect of kintop on gastrointestinal movement and its significance]. AB - OBJECTIVE: To study the effect of obesity-reducing drug Kintop on gastrointestinal movement in rats. METHODS: Eighteen Wistar rats were divided into high dose (200 mg/100 g) Kintop group, low dose (125 mg/100 g) Kintop group, and control group. After anesthesia, stomach emptying time was directly observed using methylene blue as indicator. The frequency and amplitude of intestinal movement, and movement speed of intestinal content were detected. The serum tumor necrosis factora (TNF alpha) level was measured by ELISA. RESULTS: After administration of Kintop, the stomach emptying time was prolonged markedly, movement speed of intestinal content accelerated, time of dejection increased, the intestinal movement frequency and amplitude increased. There was a negative correlation between intestinal movement frequency and serum TNF alpha level (r = 0.91, P < 0.05). CONCLUSIONS: Kintop could significantly prolong the stomach emptying time, accelerate intestinal movement. These effects are correlated with not only the increased time of dejection but also the lowered serum TNF alpha level. PMID- 11783315 TI - [Effect of 962 capsule on liver peroxidation, thymus and spleen index]. AB - OBJECTIVE: To investigate the effect of 962 capsule, a TCM compound recipe, on liver peroxidation and weight of thymus and spleen (thymus index, spleen index) in aged rats, and observe the anti-oxidation effect and the influence on immunological function in rats. METHODS: Rats were divided into young control, aged model, positive control (piracetam), 962 middle (0.9 g/kg) dose and high dose (1.8 g/kg) groups, and the medicated rats used in each group were aged rats. All tested drugs were administered for 1 month by gastrogavage. The liver peroxidation was determined by thiobarbituric acid method. The thymus index and spleen index were determined by weighing method. RESULTS: Middle and high dose of 962 capsule attenuated liver peroxidation, their liver MDA lowered, increased the thymus index of aged rats. There was no effect on spleen index in all medicated groups. CONCLUSIONS: 962 capsule could reduce liver lipid peroxidation and increase thymus index. It is suggested that 962 capsule might be beneficial in retarding aging process. PMID- 11783316 TI - [Study on 515 anti-tumor recipe in inducing leukemic HL-60 cells apoptosis]. AB - OBJECTIVE: To observe the efficacy of 515 anti-tumor recipe on inducing human myeloid leukemic HL-60 cells apoptosis. METHODS: The morphological change of apoptotic cells was observed by light microscopy and transmission electromicroscopy (TEM), and flow cytometry and TUNEL reaction to further confirm the apoptosis of HL-60 cells. RESULTS: Typical apoptosis appeared such as marginal nuclei, chromatin condensation and nuclear fragmentation could be seen by light microscopy and TEM. The drug concentration was between 0.013-0.04 g/ml. The apoptosis rate is 30% in 0.04 g/ml group at the 72nd hour, but it was only 0.8% in the control group at the same time (P < 0.01). CONCLUSIONS: The 515 anti tumor recipe can induce apoptosis in HL-60 cells. The apoptosis rate increased as the time extended. There was an enhanced efficiency of apoptosis in a dose dependent manner. PMID- 11783318 TI - [Clinical research on the integration of traditional Chinese medicine and Western medicine]. PMID- 11783317 TI - [Effect of inflammatory factor and yishen huoxue xiezhuo decoction on growth of glomerular mesangial cells in rats]. AB - OBJECTIVE: To explore the part of inflammatory factors (cytokines) and Yishen Huoxue Xiezhuo (YSHXXZ) Decoction on the proliferation of extracorporeal cultured mesangial cells (MCs) in rats. METHODS: The effects of lipopolysaccharide (LPS) and interleukin-6 (IL-6) as stimulating factors, its action on the proliferation of rat MCs were investigated by using the technique of 3H-TdR incorporation. Meanwhile, adopting serum pharmacology assay, the medicated serum of rat, containing YSHXXZ decoction was extracted and its effects on the growth of MCs were also studied. RESULTS: LPS and IL-6, in a dose-dependent and time-dependent manner, could markedly stimulate the MCS proliferation, while this stimulatory effects could be strongly antagonized by the serum containing YSHXXZ decoction. CONCLUSION: Mesangial cell is the main target cell of the action of YSHXXZ decoction, and the inhibition on MCs might be one of the mechanisms of the YSHXXZ decoction in preventing the progression of chronic glomerulonephritis. PMID- 11783319 TI - [Vascular endothelial cell injury and blood-stasis syndrome]. PMID- 11783320 TI - [Key of the study on modernization of Chinese herbal drugs: to establish a scientific modern theoretical system--hypothesis of molecular essence of drugs]. PMID- 11783321 TI - [Study on molecular mechanism of ganyang shangkang syndrome in hypertension]. AB - OBJECTIVE: To investigate the molecular mechanism of Ganyang Shangkang (Liver Yang ascending, GYSK) syndrome in hypertension. METHODS: The plasma norepinephrine (NE), epinephrine (E) contents in patients with GYSK syndrome or Ganshen Yinxu (Liver and Kidney Yin Deficiency, GSYX) syndrome who were suffered from hypertension, and normal controls were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD). The polymorphism of tyrosine hydroxylase (TH) gene in the three groups were analyzed by Southern Blot assay. The polymorphism of TH and MAOA, MAOB gene microsatellite in these groups were analyzed by polymerase chain reaction (PCR)-SSCP; meanwhile, the GYSK model by administration of single TCM preparation, Radix Aconiti preparate (RAP) in spontaneous hypertension rats (SHR). The adrenal gland medulla were examined for their TH expression at the protein level after ABC immuno histochemical staining with the TH monoclonal antibody (McAb). The adrenal TH gene mRNA expression was demonstrated by in situ hybridization with the synthesized TH oligonucleic acid probe. The results of immunohistochemistry and in situ hybridization were analyzed with the image analysis system (IAS). RESULTS: The plasma NE, E contents in patients with GYSK were more significantly increased than that in GSYX and normal controls. The TH gene amplified and the type A1 TH microsatellite D11S4046 was increased more remarkably than other groups. The TH mRNA protein expression in their adrenal tissue of the single TCM preparation RAP induced GYSK model in SHR were elevated. CONCLUSIONS: The GYSK syndrome of hypertension possesses the character as amplified TH gene and increased TH mRNA and protein. It suggested that the hyperexpression of TH is probably the mechanism of GYSK syndrome in hypertension. PMID- 11783322 TI - [Effect of longshoudan on serum tumor necrosis factor and circulating endothelial cell levels in acute cerebral infarction patients]. AB - OBJECTIVE: To investigate the effect of Longshoudan (LSD) on the serum tumor necrosis factor (TNF) and circulating endothelial cell (CEC) levels in acute cerebral infarction (ACI) patients, and the mechanism of LSD in treating ACI. METHODS: The levels of serum TNF-alpha and CEC in 40 ACI patients before and after LSD oral administration were measured by radioimmunoassay, and compared with 20 routinely treated ACI patients, and 20 healthy subjects as control group. RESULTS: (1) The levels of serum TNF-alpha and CEC in ACI patients were significantly higher than those in the control group, there was significant correlation between the increased extent and infarction size, the larger the size, the higher the levels of serum TNF-alpha and CEC; (2) In ACI patients, the serum TNF-alpha level was positively correlated with CEC level (r = 0.68, P < 0.01); (3) The serum TNF-alpha and CEC level of all ACI patients after 4 weeks were reduced, and LSD treated group was significantly lower than that of routinely treated group (P < 0.01). CONCLUSION: LSD could protect cerebrovascular endothelial cells and ischemic neurons through lowering the increased levels of serum TNF-alpha and CEC in ACI patients, and alleviate the damage of cerebrovascular endothelial cells. PMID- 11783323 TI - [Observation of therapeutic effect of Salviae miltiorrhiza and cytosine diphosphate-choline injection on patients with hypertensive cerebral hemorrhage]. AB - OBJECTIVE: To assess the effect of Salviae miltiorrhiza (SM) injection in the treatment of hypertensive cerebral hemorrhage (HCH). METHODS: Fifty-one cases (age 50-78 years, 61.2 years on average) of HCH were randomly divided into three groups (SM + cytosine diphosphate-choline (CDP-C) group and para-aminomethyl benzoic acid (PAMBA) + CDP-C group as treated group, CDP-C group as control group) to observe the outcome of the clinical treatment, hematoma absorbability and changes of ADP-platelet agglutination rate (Pag), prothrombin time(PT) and function of the liver and kidney. RESULTS: The rate of good result (GR) and moderate disability (MD) in SM group was 85.71% with the method of Glasgow outcome score (GOS), others were 47.06% and 61.54% separately, they have significant difference, P < 0.05. Among them, SM group had best result. Compared the rate of hematoma absorbability of SM group with that of PAMBA, CDP-C groups, the difference was significant, P < 0.05. It did not affect the platelet coagulative function in SM group. CONCLUSION: SM injection could effectively improve the condition of patients with HCH, and without any side effect. It is worthwhile to be used in the clinical practice. PMID- 11783324 TI - [Effect of huanyuan injection on plasma endothelin and plasma calcitonin gene related peptide in acute intracerebral hemorrhage]. AB - OBJECTIVE: To study the mechanism of Huanyuan injection in treating acute intracerebral hemorrhage. METHODS: Forty-five patients were divided into Huanyuan group and mannitol group who were treated with Huanyuan injection and mannitol intravenously for two weeks respectively. Meanwhile, the two groups were also treated with vitamin C, potassium chloride, etc, intravenously. Plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) levels were determined before and after treatment. RESULTS: After treatment for two weeks, changes of plasma ET and CGRP in mannitol group was insignificant (P > 0.05). Compared with the two treated group, There was obvious significance in plasma ET levels and CGRP content (P < 0.05). CONCLUSION: Therapeutic mechanism of Huanyuan injection in treating acute intracerebral hemorrhage were correlated to reduce plasma ET and raise the CGRP levels. PMID- 11783325 TI - [Clinical observation of elderly idiopathic nephrotic syndrome treated with integrated traditional Chinese and Western medicine]. AB - OBJECTIVE: To observe the clinical effect of integrated traditional Chinese and western medicine (TCM-WM) in treating the elderly idiopathic nephrotic syndrome (INS). METHODS: Eighty-two patients of the elderly INS were randomly divided into the TCM-WM group and the control group. Forty-one patients of the TCM-WM group were treated with prednisone, Cytoxan (CTX) and Chinese medicinal herbs according to Syndrome-type, the other 41 patients of the control group were treated with WM alone. Clinical remission rate, adverse reaction, recurrence rate and remission period were observed. RESULTS: The complete remission rate and total remission rate of the TCM-WM group were 58.5% and 85.4%, significantly higher than those of the control group (39.0%, 63.4%, P < 0.01). The adverse reaction rate of the TCM WM group (36.6%) was significantly lower than that of the control group (80.5%, P < 0.01). A follow-up of 35.1 +/- 9.7 months showed that there was no significant difference in the recurrence rate between two groups (P > 0.05), but the average remission period (30.6 +/- 3.8 months) of the TCM-WM group was significantly longer than that of the control group (12.7 +/- 3.7 months, P < 0.01). CONCLUSION: TCM-WM treatment is obviously superior to treatment with WM alone in increasing clinical remission rate, relieving adverse reaction rate and extending remission period. PMID- 11783326 TI - [Cardiac protective effects of tetramethylpyrazine in patients performed open heart operation with cardiopulmonary bypass]. AB - OBJECTIVE: To study the cardiac protective effects of tetramethylpyrazine (TMP) on patients undergoing cardiac operation. METHODS: Twelve patients with rheumatic heart disease were randomly divided into the TMP group and the control group, 6 in each group. The changes of hemodynamics, serum creatine phosphokinase (CPK), creatine phosphokinase isoenzyme (CPK-MB) levels were observed before, during and 72 hours after operation. RESULTS: The hemodynamic indexes in the TMP group were better than those in the control group after operation, the serum CPK, CPK-MB levels measuring 12 h, 24 h and 48 h after operation in the TMP group were lower than those in the control group. CONCLUSION: TMP has good cardiac protective function in patients undergoing cardiac operation in improving cardial function and reducing the release of myocardial enzymes. PMID- 11783327 TI - [Effect of 2/100 Hz transcutaneous electrical nerve stimulation on sexual dysfunction and serum sex hormone of heroin addicts]. AB - OBJECTIVE: To evaluate the effect of 2/100 Hz electrical stimulation produced by Han's acupoint nerve stimulator (HANS) in treating heroin induced sex dysfunction. METHODS: Thirty-three heroin addicts were randomly divided into 2 groups to receive either buprenorphine (BPN group, n = 16) or HANS plus small dose of BPN (HANS group, n = 17) for 14 days. The doses of BPN were tailored according to individual requirement that could totally abolish withdrawal syndrome. The frequency of HANS was 2 Hz and 100 Hz shifting automatically, each lasting for 3 seconds. The stimulation was applied to 8 acupoints, the Hegu and Laogong of one upper limb, Neiguan and Waiguan of another limb, Sanyinjiao and Xingjian of both lower limbs, for 30 min. The therapy was carried out 3-4 times per day in the initial two weeks of treatment, and reduced to 1-2 times per day in the following 2 weeks. RESULTS: (1) The urine analysis for morphine in both groups turned to negative 14 days after treatment. (2) After 2 weeks of treatment, the composite score (Visual Analog Scale, VAS) of sexual function in HANS group showed a 102% increase (P < 0.01) compared with before treatment and was 107% of that in the BPN group (P < 0.01). (3) After 4 weeks treatment the serum concentration of luteinizing hormone (LH) and testosterone (T) in the HANS group showed a 137% and 118% increase respectively compared with those before treatment (P < 0.05), and the level of LH was 79.6% of that in the BPN group (P < 0.05). CONCLUSION: The 2/100 Hz transcutaneous electrical stimulation produced by Han's acupoint nerve stimulator could improve the recovery of sexual function and raise the serum concentration of LH and T in heroin addicts. PMID- 11783328 TI - [Effect of xinmaitong capsule on total ischemia burden in coronary heart disease patients with myocardial ischemia and analysis of its therapeutical mechanism]. AB - OBJECTIVE: To assess the effect of Xinmaitong (XMT) capsule in treating ischemical cardiac disease. METHODS: Sixty coronary heart disease (CHD) patients with myocardial ischemia were divided randomly into two groups. XMT group (30 cases) was treated with XMT plus western medicine, and control group (30 cases) with western medicine alone. The changes of the scores for clinical symptoms, the total ischemia burden (TIB), the plasma endothelin (ET), the nitric oxide (NO), the superoxide dismutase (SOD), and the malonyldialdeyde (MDA) levels were observed before and after treatment. RESULTS: After treatment with XMT the scores of clinical symptoms, TIB, ET and MDA levels were significantly decreased (P < 0.01), the levels of NO and SOD were significantly increased (P < 0.01) in the XMT group, comparing with the control group these changes were statistically different (P < 0.01). CONCLUSIONS: XMT capsule can act against myocardial ischemia effectively, one of the mechanisms of which is protecting the function of vascular endothelium and resisting lipid peroxidation injury. The effects of adding XMT capsule on conventional treatment of western medicine were better than those of using western medicine alone. PMID- 11783329 TI - [Clinical observation on therapeutic effect of xinyikang oral liquid in treating 92 patients of viral myocarditis]. AB - OBJECTIVE: To observe the clinical effect of Xinyikang Oral Liquid (XYK) in treating viral myocarditis patients of Qi-Yin Deficiency and Evil-Toxin Encroaching Heart Type. METHODS: Randomized controlled method was adopted, the 92 cases in the XYK group received XYK and 30 cases in the control group received Qidong Yixin oral liquid treatment for 4 weeks as a therapeutic course. Their symptoms, signs, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), lactate, aspartate aminotransferase (AST) dehydrogenase (LDH), creatine phosphokinase (CPK), creatine phosphokinase isoenzyme (CPK-MB), electrocardiogram (ECG) and dynamic ECG changes before and after treatment were observed. RESULTS: The improvement on chest stuffiness, short breath, fatigue and spontaneous perspiration in the treatment group was better than those in the control group (P < 0.05) and XYK showed obvious improving effect on ESR, AST, LDH, CPK and CPK-MB (P < 0.01 or 0.05). There was no adverse reaction or side-toxic effects revealed in using XYK. CONCLUSION: XYK has significant therapeutic effect in treating viral myocarditis. PMID- 11783330 TI - [Effect of tetramethylpyrazine on platelet agglutination of patients undergoing cardiac valve replacement operation]. PMID- 11783331 TI - [Clinical and experimental studies on clearing away stomach-heat purging fire and nourishing yin principle in treating patients of recurrent aphthae]. AB - OBJECTIVE: To observe the therapeutic effect of Kouchuangping granule (KCP) on recurrent aphthae and explore its mechanism. METHODS: One hundred and forty-eight patients treated with KCP were observed and compared with 49 patients treated with tripterygii multiglycoside tablet as control in controlling relapse, prolonging intermittent period, improving local symptom and the influence on humoral and cellular immunity. In animal experiment, the effects of KCP on immunologic function, anti-exudation, anti-inflammation and analgesia were studied. RESULTS: The clinical markedly effective and cure rate of the KCP group was 62.8% and the total effective rate was 89.9%, which were significantly higher than those of the control group (40.8% and 75.5%, P < 0.01, P < 0.05). In the KCP group, the intermittent period of aphthous ulcer recurrence was prolonged to 6 months and the local symptoms were markedly improved, the differences were significant as compared with those before treatment and those in the control group (P < 0.01 or 0.05). The KCP showed effects in suppressing humoral immunity and enhancing cellular immunity. Results of experimental study showed that KCP could inhibit the supernormal reaction of cellular immunity to prevent and treat the hypersensitivity caused erosion and ulceration of mucosae, inhibit capillary permeability and WBC migration and abate the 5-hydroxytryptamine (5-HT) and histamine induced local swelling and pain. CONCLUSION: KCP has a significant effect in treating recurrent aphthae, the mechanism might be related with its effect on immunoregulation, anti-inflammation and anti-exudation. PMID- 11783332 TI - [Stress on scientific morality, advocate the practical and realistic style]. PMID- 11783333 TI - [Influence of feiliuping No. 2 on platelet surface glycoprotein expression in mid late stage lung cancer patients]. AB - OBJECTIVE: To explore the influence of Feiliuping NO. 2 (FLP), a Chinese herbal preparation for reinforcing Qi, nourishing Yin, activating blood circulation and detoxifying, on surface glycoprotein expression (SGPE) and activated condition of platelet in mid-late stage lung cancer patients. METHODS: Changes of platelet surface expression of CD41/CD42a, CD36/TSP, CD62/CD63, CD9 and CD31 were measured before and after FLP treatment by using flow cytometer in 30 cases of mid-late stage lung cancer. RESULTS: The SGPE and activated condition of platelet in mid late stage lung cancer patients were significantly higher than those of healthy person, and both could be reduced partly by FLP. CONCLUSION: FLP could influence the SGPE and activate condition of platelet in lung cancer patients. PMID- 11783335 TI - [Effect of gandou decoction on copper metabolism of skin fibroblast of hepatolenticular degeneration model]. AB - OBJECTIVE: To explore the cytological mechanism of Gandou Decoction (GDD) in treating hepatolenticular degeneration (HLD). METHODS: Twenty-three in vitro models of cultured skin fibroblast of HLD were established to observe the intracellular change of microelements (Cu2+, Zn2+, etc.) content before and after adding rabbit's serum containing GDD. RESULTS: After being treated with GDD contained serum for 24 hours, the intracellular content of Cu2+ decreased from (80.94 +/- 34.76) ng/mg to (46.90 +/- 22.14) ng/mg, P < 0.01, while that of Zn2+ increased from (140.43 +/- 33.81) ng/mg to (151.43 +/- 37.83) ng/mg, P < 0.01. CONCLUSION: GDD is quite effective in removing the intracellular copper and increasing the intracellular zinc. PMID- 11783334 TI - [Clinical observation on ganrening granule in treating common cold]. AB - OBJECTIVE: To explore the therapeutic effect of Ganrening Granule (GRN) in treating common cold. METHODS: Four hundred cases of common cold were randomly divided into three groups, the GRN group (160 Patients), the control group (100 Patients) and the opened group (140 Patients). The changes in symptoms and body temperature of patients were observed before and after treatment by single blind method, and the therapeutic effect was assessed according to the "Guideline of Clinical Research of TCM New Drugs". RESULTS: The markedly effective rate and total effective rate of the GRN group were 81.25% and 96.88% respectively, while those of the control group were 44.44% and 88.00% respectively. The difference between the two groups was significant (P < 0.01). GRN showed significant effect in subsiding fever. CONCLUSION: GRN has good effect in treating common cold (Syndrome of both Weifen and Qifen). No adverse effect was found in the clinical trial. PMID- 11783336 TI - [Effect of xiaoqinglong decoction drug-serum on degranulation and histamine releasing of peritoneal mastocyte in sensitized rats]. AB - OBJECTIVE: To study the mechanism of anti-allergic effect of Xiaoqinglong Decoction (XQLD). METHODS: The influence of XQLD drug-serum frozen powder on degranulation and histamine releasing of peritoneal mastocyte in sensitized rats was examined by morphologic and fluorimetric method. RESULTS: The drug-serum prepared by serum obtained 2 hours after medication for 15 min has obvious inhibitory effect on degranulation and histamine releasing of peritoneal mastocyte which showed a basically unified time-effect relationship. CONCLUSION: The anti-allergic effect of XQLD is related with the allergic medium (histamine) inhibition of releasing of peritoneal mastocyte. PMID- 11783337 TI - [Experimental study on effect of bushen yijing recipe in delaying senility of bone and brain of aged male rats]. AB - OBJECTIVE: To evaluate the effect of Bushen Yijing recipe (BSYJR) in delaying senility of bone and brain of aged male rats and infer its mechanism in delaying systemic senility. METHODS: Forty male SD rats, 24 months old were randomly divided into 4 groups, the baseline control group, the aged control group (30 months old), the BSYJR high dose group and the BSYJR low dose group. The latter two groups received BSYJR treatment from 24 months old to 30 months old. Bone indexes (bone density of the proximal, middle and distal segments of left femur and break bending load of right femur) and brain indexes (binding capacity of M receptor and cholinesterase activity of brain) were measured after responding treatment. RESULTS: In bone, BSYJR could not only increase the bone mineral density in various segments of femur, but also raise the bending break load of femur dose-effect dependently. In brain, BSYJR could both up-regulate the binding capacity of M receptor and inhibit the activity of cholinesterase. CONCLUSION: BSYJR could delay the senility of bone and brain in male rats, inferring that it might regulate integrally the abnormality of aging in Kidney Asthenia and Essence Deficiency through mediation of nerve-endocrine-immunity network. PMID- 11783338 TI - [Effect of kidney-replenishing herbs on ovarian function of dexamethasone-induced osteoporosis in rats]. AB - OBJECTIVE: To investigate the effect of Kidney-replenishing herbs (KRH) on ovarian function of experimental rats with dexamethasone-induced osteoporosis (OP). METHODS: Radioimmunoassay was used to analyse blood level of growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), testosterone (T) and prolactin (PRL) of animals and data of three groups, the normal control group, the pathologic control group (non treated OP model) and the treated group (model rats treated with KRH) were compared. Weight and histomorphological features of ovary and uterus of the rats were also observed. RESULTS: As compared with the normal control group, levels of GH, LH, FSH, E2 and P in the pathologic control group were significantly lowered (P < 0.05), and the weight of ovary and uterus decreased (P < 0.05). In comparison of the treated group and the pathologic group, GH, LH, FSH, E2 and P levels were significantly higher and weight of ovary and uterus heavier in the treated group (P < 0.05). No obvious changes occurred in T and PRL levels. KRH showed markedly improving effect on the ovarian and uterine morphological construction of rats. CONCLUSIONS: KRH could elevate the level of GH, LH, FSH, E2 and P, increase the weight and improve the histomorphologic features of ovary and uterus in OP rats, it demonstrated that KRH has therapeutic effect in treating dexamethasone-induced OP rats. PMID- 11783339 TI - [Contrast study on effect of shenkang injection and benazepril on human glomerular mesangial extracellular matrix]. AB - OBJECTIVE: To explore the intensity of inhibition of Shenkang Injection (SKI) and Benazepril on various ingredients of human glomerular mesangial extracellular matrix (ECM). METHODS: Effect of SKI, a herbal preparation for lowering adverse Qi, despelling turbidness, supplementing Qi and activating circulation, and Benazepril were observed by cultured glomerular mesangial cell technique in vitro. RESULTS: SKI could inhibit the fibronetin, laminin, and type IV collagen of ECM, and the action was dose-dependent. Benazepril could also inhibit the fibronetin and type IV collagen of ECM but was weaker in intensity. CONCLUSION: The effect of SKI was superior to Benazepril in inhibiting ECM. PMID- 11783340 TI - [Treatment of bacterial peritonitis with dachengqi decoction and rhubarb in mice]. AB - OBJECTIVE: To observe the antiseptic effect of Dachengqi Decoction (DCQD) or rhubarb, one of the ingredients of DCQD in mice. METHODS: The model mice were established by peritoneal injection of Escherichia coli (10(8)/ml) or Proteus vulgaris (10(6)/ml) respectively. DCQD or rhubarb was given from 2 days before to 2 days after modelling for preventing and treating. RESULTS: The mortality and bacteremia occurrence of the treatment group were significantly lower than those of the control group (P < 0.05). Both DCQD and rhubarb showed protective effect on Escherichia. coli or Proteus vulgaris infection in mice. The cardiac blood smear and culture of survival mice in prevention plus treatment group and model group showed negative (bacteria) results but those of dead mice showed positive result. CONCLUSION: DCQD and rhubarb have excellent bactericidal effect. PMID- 11783341 TI - [Puzzle and countermeasure in studying principle and methods of traditional Chinese medicine treatment]. PMID- 11783342 TI - [Current status of researches on essence of typing of hypertension based on syndrome differentiation of traditional Chinese medicine]. PMID- 11783343 TI - [Current status and prospects of experimental study of psychological stress in traditional Chinese medicine]. PMID- 11783344 TI - [Secretion and regulation of nitric oxide in ovarian granular cell]. AB - OBJECTIVE: To investigate the relationship between nitric oxide (NO) secreted by ovarian granular cell and interleukin-1 beta (IL-1 beta), and their functions in estrogen synthesis. METHODS: The human ovarian granular cells recovered from follicular fluid were cultured with IL-1 beta or NO donor. RESULTS: The quantity of NO cultured with or without IL-1 beta addition were (537 +/- 23) mumol/L, (411 +/- 15) mumol/L respectively. The former was significantly higher than the latter (P < 0.01). The estradiol, progesterone synthesis and aromatizing enzyme activity in the media with the addition of NO donor were (1,234 +/- 136) micrograms/L, (988 +/- 103) micrograms/L, (0.422 +/- 0.052) Ci/ml, while as they were (1,792 +/ 103) micrograms/L, (2,486 +/- 123) micrograms/L, (0.833 +/- 0.012) Ci/ml, in the media without the addition of NO donor. The estradiol progesterone synthesis and aromatizing enzyme activity in the media with NO donor decreased significantly as compared with the group without NO donor (P < 0.01, P < 0.001, P < 0.01). CONCLUSIONS: Ovarian granulosa cells may secrete NO, and the secretion may be regulated by IL-1 beta. They may be involved in the ovulation at the preovulatory stage and regulation of ovary steroids synthesis. PMID- 11783345 TI - [Clinical and pathological analysis on 106 cases with uterine sarcoma]. AB - OBJECTIVE: To analyze the clinical features and factors affecting the prognosis of uterine sarcoma with different histological types. METHODS: One hundred and six cases with uterine sarcoma treated were analyzed retrospectively, among which there were 67 cases with leiomyosarcoma (63.2%), 23 with malignant endometrial interstitial sarcomas (21.7%), 16 with malignant Mullerian mixed tumor (15.1%). According to Union Internationale Contre le Cancer (UICC) staging, 70 cases were on stage I, 12 cases were on stage II, 19 cases belonged to stage III, and 5 cases belonged to stage IV. RESULTS: (1) The patients with leiomyosarcoma and endometrial interstitial sarcoma were relatively younger, the patients of them aged under 50 amounted to 70.1% (47/67) and 60.9% (14/23) respectively, and those aged under 40 amounted to 29.9% (20/67) and 39.1% (9/23) respectively. The patients usually manifested with abnormal vaginal bleeding (67.0%), palpable mass of lower abdomen (32.1%), vaginal discharge (27.4%), pain on lower abdomen (28.4%), symptoms of oppression (25.5%), and discomfort feeling (28.3%). (2) The rate of preoperative diagnosis was 65.9%, especially that of leiomyosarcoma was lowest (42.9%). (3) In treatment, 16.0% of patients was treated by hysterectomy; bilateral salpingo-oophorectomy and pelvic lymphadenectomy; 75.5% of them by hysterectomy and bilateral salpingo-oophorectomy; after operation, 74.5% of them were treated by chemotherapy, 11.3% by radiotherapy, 6.6% by additional progesterone. (4) The survival period of the patients was related to pathologic types and clinical stages and ages of the patients. The prognosis of the patients with leiomyosarcoma younger earlier stage was better. CONCLUSIONS: The clinical symptom of uterine sarcoma is nonspecific (mostly abnormal vaginal bleeding) and the prognosis is poor. The patients with leiomyosarcoma are younger and have better prognosis, but the rate of preoperative diagnosis is low. The prognosis of uterine sarcoma is related to pathologic types, clinical stage and ages of the patients. PMID- 11783346 TI - [Expression of estrogen receptor beta mRNA in endometrial carcinoma and its significance]. AB - OBJECTIVE: To investigate the expression of estrogen receptor beta (ER beta) mRNA and its significance in endometrial carcinoma. METHODS: Thirty-six normal and 45 cancer tissue samples of endometrium were obtained, and the RNA was isolated from the tissues by the acid guanidium thiocyanate-phenol-chloroform extraction method. Reverse-transcription polymerase chain reaction (RT-PCR) was used to amplify the ER beta exon 5 wild type mRNA (ER beta WT) and splicing variant mRNA (ER beta E5SV). Electrophoresis of polymerase chain reaction product was performed and the ratio of ER beta E5SV/ER beta WT was calculated. The sequencing of ER beta E5SV and ER beta WT was carried out by express DNA sequencer. RESULTS: ER beta E5SV and ER beta WT were both expressed in normal endometrium and endometrial cancer tissues. A region of 139 bp from base pair 812 to 950 (the hormone-binding domain) was found to be deleted in ER beta E5SV sequence as compared to ER beta WT. The quantity of ER beta E5SV was more than that of ER beta WT in every normal endometrium, and was less in every endometrial cancer, the ratio of ER beta E5SV/ER beta WT was 2.47 +/- 0.99 in normal endometrium, and 0.55 +/- 0.12 in endometrial cancer (P < 0.0001). The ratio of ER beta E5SV/ER beta WT decreased with the grade from 1 to 3 (P < 0.01). CONCLUSION: Overexpression of ER beta WT relative to ER beta E5SV may correlate with the genesis of endometrial carcinoma. PMID- 11783347 TI - [Anti-tumor immune response to cervical carcinoma induced by costimulatory molecule B7 gene in mice]. AB - OBJECTIVE: To investigate the effects of B7 costimulatory molecule on inducing anti-tumor immune response to cervical carcinoma in vivo. METHODS: We transfected mouse B7 gene into murine cervix carcinoma cell line U14 by electroporation, and obtained several high-expressed mB7 U14 cell clonal strains (B7+ U14) detected by reverse transcription polymerase chain reaction (RT-PCR). In vivo experiments: (1) 1 x 10(7) B7+ U14 cells were inoculated into the back of inbred 615-strain mice by subcutaneously injection to determine their tumorigenicity (n = 6). (2) The mice primed by B7+ U14 (1 x 10(6)) cells were re-challenged with 1 x 10(7) wild type U14 to observe the immune protection of these mice against the wild type U14 (n = 6). As control, (3) wild type U14 cells were inoculated the same as the experimental group (1) (n = 6). (4) The mice both primed and re-challenged with 1 x 10(7) wild type U14 the same as the experimental group (2) (n = 6). All mice lifetime and tumor sizes were recorded. In vitro cytotoxiaty assay: the mice were immunized with B7+ U14 or the wild type U14 by intraperitoneal injection (n = 4 x 2) and two weeks late those mice spleen cells were obtained and cultured for two days. The cytotoxiaty of these cells against the wild U14 was detected by methyl thiazolyl tetrazolium assay. RESULTS: RT-PCR showed positive results in B7+ U14 cells, while negative in U14 cells. In vivo experiment: (1) after the inoculation of the B7+ U14 cells into the back of inbred mice, they lost their tumorigenicity greatly compared to wild type U14 (P < 0.01). (2) Primed by B7+ U14, mice protected themselves effectively against rechallenged (P < 0.01). In vitro cytotoxiaty assay, the cytotoxic T lymphocytes (CTLs) induced by B7+ U14 had a higher cytotoxiaty against the wild type U14 than that induced by wild type U14 (P < 0.01). CONCLUSIONS: Cervical carcinoma cells transfected with constimulatory molecules B7 gene can decrease their tumorigenicity greatly, and induce anti-tumor immune protection of inbred mice against wild type U14 cells re challenged. The results suggest that to transfect B7 gene into cervical cancer expression may be an effect method for treating cervical cancer in clinical. PMID- 11783348 TI - [The evaluation of fetal cardiac function in diabetic pregnancies]. AB - OBJECTIVE: To assess fetal cardiac hypertrophy and ventricular function in fetuses of diabetic mothers. METHODS: Study group was consist of 23 fetuses of diabetic pregnancies. Control group was consist of 108 fetuses of normal pregnancies. Cardiac size was measured by ultrasound as inter-ventricular septal (IVS) thickness and ventricular diastolic and systolic (VD and VS) dimensions and perimeter. Cardiac function was expressed as ventricular shortening fraction 1 (VSF1) (ventricular diastolic perimeter-ventricular systolic perimeter/ventricular diastolic perimeter) and ventricular shortening fraction 2 (VSF2) (ventricular diastolic dimension-Ventricular systolic dimension/ventricular diastolic dimension). Fetal birth weight was recorded. RESULTS: IVS of study group (6.1 +/- 0.7) mm, which was significantly thicker than IVS of control group (4.4 +/- 0.7) mm. Left ventricular diastolic dimension (LVDD) and Left ventricular systolic dimension (LVSD) of study group were (3.3 +/ 0.8) cm2 and (2.2 +/- 0.6) cm2, which were greater than those of control group (2.6 +/- 0.6) cm2 and (2.0 +/- 0.5) cm2. Right ventricular diastolic dimension (RVDD) and Right ventricular systolic dimension (RVSD) of study group were (3.9 +/- 0.7) cm2 and (2.6 +/- 0.7) cm2, which were also greater than those of control group (3.5 +/- 0.5) cm2 and (2.4 +/- 0.7) cm2. Left ventricular shortening fraction 1 of left ventricular (LVSF1) of study group was 0.20 +/- 0.07, which was greater than that of control group (0.12 +/- 0.04). LVSF2 of study group was 0.35 +/- 0.11, which was greater than that of control group too (0.23 +/- 0.10). Right ventricular shortening fraction 1 of left ventricular (RVSF1) of study group was 0.19 +/- 0.05, which was greater than that of control group (0.13 +/- 0.11). RVSF2 of study group was 0.33 +/- 0.09, which was greater than that of control group (0.23 +/- 0.14). Estimated fetal birth weight of study group was (4,076 +/- 608) g, which was greater than that of control group (3,440 +/- 377) g. CONCLUSION: These findings showed that fetal hyperinsulinemia result in fetal weight increasing, global cardiac enlarger inter-ventricular septal thickness larger and revealed hypercontractilty of ventricle in fetuses of diabetes mothers. PMID- 11783349 TI - [Study on association of vascular endothelial growth factor with the pathogenesis of pregnancy induced hypertension]. AB - OBJECTIVE: To investigate relationship between the vascular endothelial growth factor (VEGF) and the pathogenesis of pregnancy induced hypertension syndrome (PIHs). METHODS: Twenty-three women with PIHs and twenty normal pregnant women were studied. The levels of VEGF in maternal and umbilical venous serum, placenta and decidual tissue from normal pregnancy and PIHs women were detected by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry. Furthermore, the expression of VEGF mRNA in placenta and decidua was examined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: (1) The levels of VEGF in maternal blood were significantly lower in PIHs women than that in normal pregnancies women (10.4 +/- 3.8) ng/L and (17.0 +/- 9.3) ng/L (P < 0.01). (2) The average gray of VEGF was determined on sections of placenta and decidua from PIHs or pregnancies women by computer image analysis. The expression of VEGF in placenta and decidua (69.0 +/- 8.9) and (55.0 +/- 7.3) was decreased significantly in PIHs women than that in normal pregnancies women (75.0 +/- 9.0) and (60.5 +/- 6.4, P < 0.05). (3) The transcription levels of the VEGF mRNA in placenta and decidua were increased significantly in PIHs women than those in normal pregnancies women (4.6 +/- 3.2 vs 2.8 +/- 1.0; 6.3 +/- 2.9 vs 3.9 +/- 1.5, P < 0.01). CONCLUSIONS: These findings suggested that the abnormal expression of VEGF in PIHs occurred within the low-stream of genic transcription. It was considered that the abnormal expression of VEGF may play an important role in the pathogenesis of placental ischemia in PIHs. PMID- 11783350 TI - [Application of inter-fluorescence in situ hybridization of chromosome 13/21 alpha satellite probe in amniotic cells for prenatal diagnosis trisomy 21 syndrome]. AB - OBJECTIVE: To investigate the prenatal diagnosis of trisomy 21 syndrome using chromosome 13/21 alpha satellite probe fluorescence in situ hybridization (FISH) on uncultured interphase cells from amniotic fluid. METHODS: The interphase amniocytes of 10 fetuses who were detected normal and 3 fetus who were detected trisomy by prenatal cytogenetic diagnosis were selected. We did FISH which used chromosome 13/21 alpha satellite probe directly on the uncultured amniocytes of these 13 samples. RESULTS: The total rate of the hybridization was 36.7% and 38.6% in control group and observation group respectively, showed no significantly difference. There were four signals in the nucleus, two groups were 36.5% and 3.9% respectively, there were five signals in the nucleus, two groups were 4.0% and 36.1% respectively. The control group and observation group showed significantly difference by the statistical chi 2 values (P < 0.01). Trisomy 21 syndrome was diagnosed when nucleus of five signals accounted for more than 36.1%. CONCLUSION: FISH with Chromosome 13/21 alpha satellite probe is a valuable method for rapid prenatal diagnosis of trisomy 21 syndrome. PMID- 11783351 TI - [Effect of hypoxia-ischemia on cysteinyl aspartate-specific proteinases activity in cerebral tissue of neonatal rat]. AB - OBJECTIVE: To study the effect of hypoxia-ischemia on cysteinyl aspartate specific proteinases (caspase-3) activity in cerebral tissue of neonatal rat and probe into its significance. METHODS: To induce hypoxio-ischemic brain damage (HIBD), the left carotid artery of rats at day 7 was ligated and animals were exposed to 8% oxygen for 2 hours. 0.5, 12, 24, and 48 hours after HIBD, both ipsilateral and contralateral cerebral tissue were ditected and homogenized, caspase-3 activity was measured by cleavage of the colorimetric substrate DEVD pNA. RESULTS: Caspase-3 activity in ipsilateral cerebral tissue increased gradually after HIBD and peaked at 24 hours, and then decreased significantly at 48 hours(P < 0.001). There were no significant changes in caspase-3 activity in the contralateral tissue at all time points (P > 0.05). CONCLUSIONS: Significant activation of caspase-3 after cerebral hypoxia-ischemia strongly suggests that apoptosis is involved in HIBD. Application of caspase inhibitors or other anti apoptotic agents may become a new therapeutics of HIBD. PMID- 11783352 TI - [Expression of endometrial leukaemia inhibitory factor gene in patients with unexplained infertility]. AB - OBJECTIVE: To investigate the expression of endometrial leukaemia inhibitory factor(LIF) gene in patients with unexplained infertility. METHODS: By a quantitative reverse transcription-polymerase chain reaction (RT-PCR), the expression of LIF gene on endometrium during mid-luteal phase was detected in 35 unexplained infertility (infertility group) cases and 20 infertile cases due to tubal obstruction or male factor (control group). RESULTS: The level of LIF mRNA expression on endometrium during mid-luteal phase in infertility group was 0.448 +/- 0.239, significantly lower than those in the control group (1.093 +/- 0.761, P < 0.01). CONCLUSIONS: Our findings suggested LIF might play an important role in the process of implantation. The decreased expression of LIF gene might be one of the major causes of unexplained infertility. PMID- 11783353 TI - [Study on the distribution of lymphocyte subsets in the eutopic and ectopic endometrium of women with endometriosis]. AB - OBJECTIVE: To investigate the abnormal distribution of lymphocytes in eutopic and ectopic endometrium of patients with endometriosis and its significance. METHODS: In 43 cases, biopsies of ectopic tissues were taken by laparoscopy and laparotomy from patients with endometriosis and eutopic endometrium by curettage at the same time. In 19 cases, eutopic endometrium was taken from hysterectomy for myomatous uterus. Immunohistochemical techniques were employed to demonstrate the difference in the number and ratio of the lymphocyte subsets between the patients with endometriosis and the controls. RESULTS: In the patients with endometriosis, in the proliferative phase, ectopic endometrium contained respectively CD3+ CD8+ T cells and CD68+ macrophages (67.2 +/- 13.5)/5 HP, (45.0 +/- 14.0)/5 HP and (37.2 +/- 10.6)/5 HP, significantly higher then that in the eutopic endometrium (52.4 +/- 11.3)/5 HP (P < 0.01), (32.5 +/- 10.0)/5 HP (P < 0.05), and (30.7 +/- 10.3)/5 HP, and also higher as compared with the control group (52.1 +/- 14.9)/5 HP (P < 0.05), (28.9 +/- 12.7)/5 HP (P < 0.01), (26.3 +/- 9.3)/5 HP (P < 0.05); in the secretory phade, CD8+/CD4+, and CD68+ content was respectively 3.5 +/- 1.2, (40.3 +/- 12.2)/5 HP, higher than that in the control group, 3.2 +/- 0.8 (P < 0.05), (28.6 +/- 10.6)/5 HP (P < 0.01). The number of macrophages was also significantly increased. No cyclic changes in the number of lymphocytes in each subpopulation in ectopic endometrium were found. CONCLUSIONS: In the patients with endometriosis, the changes in T lymphocytes and macrophages are mainly on the endometriotic sites. The infiltration of many lymphocytes and macrophages into the ectopic endometrium formed a chronic inflammatory process. The lymphocytes are not able to clear the ectopic endometrium in the late stages of endometrium, on the contrary, they stimulate the further growth of the endometrium. PMID- 11783354 TI - [Expression of monocyte chemotacticp protein-1 in the eutopic endometrium of women with endometriosis]. AB - OBJECTIVE: To examine the expression of monocyte chemotactic protein-1 (MCP-1) messenger ribonucleic acid (mRNA) in the endometrium of patients with and without endometriosis. METHODS: A reverse transcription-polymerase chain reaction (RT PCR) method was utilized to examine and quantitate MCP-1 mRNA expressions and levels in the eutopic endometrium. Thirty patients with endometriosis were included as study group, and 20 patients without endometriosis selected as control group. RESULTS: 26 (87%) of 30 samples of endometrium from patients with endometriosis expressed MCP-1 mRNA, 19 of which were strong expression, while 15 (75%) of 20 samples of endometrium from patients without endometriosis express MCP-1 mRNA (P > 0.05). When endometriosis were grouped by Revised American Fertility Society (RAFS) stages, there was no obvious correlation between stage and MCP-1 mRNA expression level (P > 0.05). Semi-quantitative PCR showed the expression level of MCP-1 in endometrium of patients with endometriosis were higher than those of patients without endometriosis (0.746 +/- 0.345 Vs 0.460 +/- 0.341 respectively, P < 0.05). CONCLUSIONS: The MCP-1 mRNA is over expressed in the eutopic endometrium from patients with endometriosis, which may play some roles on the pathogenesis of endometriosis. PMID- 11783355 TI - [Application of sequential culture in assisted reproductive technique]. AB - OBJECTIVE: To investigate the effects of sequential culture technique on the outcomes of in vitro fertilization-embryo transfer(IVF-ET). METHODS: Sequential culture media were used in 47 IVF-ET cycles, and conventional medium in 114 cycles. The fertilization rate, cleavage rate and speed, good embryo rate and pregnancy rate were compared between these 2 groups. RESULTS: There were significantly higher embryo cleavage and quality score rate, pregnancy rate (97.9%, 64.4%, 46.7%) in sequential media group as compared those in conventional medium group (89.7%, 40.2%, 28.2%). CONCLUSION: Sequential culture system is more suitable for the development of cultured human oocytes and embryos. PMID- 11783356 TI - [Effects of leptin on estradiol and progesterone production by human luteinized granulosa cells in vitro]. AB - OBJECTIVE: To investigate the effects of leptin on steroidogenesis of human luteinized granulosa cell in vitro. METHODS: Human luteinized granulosa cells were isolated from follicular fluid obtained during oocyte retrieval of in vitro fertilization-embryo transfer program and were cultured with M199 medium plus various concentration of leptin (0, 10, 30, 100, 300 ng/ml), human menopausal gonadotropin (hMG, 0, 0.1, 0.2, 0.5, 1, 2, 5, 10 IU/ml) and testosterone 100 micrograms/ml. For 2 days the media were collected for estradiol and progesterone measurements. RESULTS: Addition of leptin alone did not alter estradiol and progesterone production (P > 0.05) by human luteinized granulosa cells. Leptin of 10-30 ng/ml concentrations caused a dose-dependent inhibition of estradiol production (P < 0.05) while greater than 0.5 IU/ml of hMG were added. There was no effect of leptin on hMG-stimulated progesterone production (P > 0.05). CONCLUSION: Leptin can directly inhibit hMG-stimulated estradiol production by human luteinized granulosa cells in vitro, but has no effect on progesterone production. Leptin may play an important role in follicle development and luteinization. PMID- 11783357 TI - [Relationship between follicular development and insulin like growth factor I receptor in stimulated cycles]. AB - OBJECTIVE: To investigate the number of follicles and insulin-like growth factor I receptor (IGF-I R) in stimulated cycles. METHOD: IGF-I R mRNA and IGF-I R in granulosa cells obtained during oocyte retrieval were respectively measured by reverse transcript polymerase chain reaction (RT-PCR) and Western blot technique. RESULTS: The expression of IGF-I R mRNA in poor responders (follicles < or = 3) was much lower than in normal responders (follicles 4-13) and high responders (follicles > or = 14) (1.70 +/- 0.23, 2.92 +/- 0.49, 4.22 +/- 1.50 respectively). Similar results were obtained for IGF-I R (1.32 +/- 0.31, 2.01 +/- 0.72, 4.39 +/- 2.31 respectively). CONCLUSION: The expression of IGF-I R correlated with the effects of gonadotropin hormone on follicular development. PMID- 11783358 TI - [The recent research on etiology of pregnancy induced hypertension disorders]. PMID- 11783359 TI - [The national symposium on pregnancy induced hypertension]. PMID- 11783360 TI - [The placental immunopathology of intrauterine growth retardation]. AB - OBJECTIVE: To observe the immune complex distribution in placenta of intrauterine growth retardation (IUGR). METHOD: Using immunohistochemical technique (SP method), authors studied the deposition of IgG and IgM in the placenta of idiopathic IUGR patients (including 8 samples of (ACA)-positive and 14 samples of ACA-negative) and patients with Pregnancy induced hypertension (PIH) complicated IUGR. RESULTS: There is no significant difference of IgG deposition in villous vessels among the three groups. The positive rate of IgM in villous vessels, the positive rate of IgG, IgM in decidual vessels and the deposition of IgM in syncytiotrophoblast of both idiopathic IUGR and PIH complicated IUGR were much higher than those of control group (P > 0.05). The positive rates of IgG, IgM in decidual vessels and villous vessels between the ACA-positive group and ACA negative group in the idiopathic IUGR were not significantly different. CONCLUSIONS: The immunopathological lesion in placenta might play an important role in the development of IUGR. Idiopathic IUGR and PIH complicated IUGR have the similar placental immunopathological changes. The etiology of IUGR induced by ACA needs more studies. PMID- 11783361 TI - [Changes of plasma level of neuropeptide Y in patients with pregnancy induced hypertension]. AB - OBJECTIVE: To investigate the changes and its clinical significance of plasma neuropeptide Y (NPY) concentration in patients with pregnancy induced hypertension (PIH). METHODS: Plasma NPY levels were detected by radioimmunoassay in 30 patients with PIH, 20 normal non-pregnant women and 23 normal pregnant women. The PIH group was subdivided into mild, moderate and Severe subgroups, and the NPY concentration was also measured in these subgroups respectively at admission and one week after delivery. RESULTS: The plasma NPY levels in patients with PIH [(164.16 +/- 68.32) ng/L] were significantly higher than those of normal non-pregnant women and normal pregnancies [(86.60 +/- 20.65) ng/L, (82.42 +/- 12.46) ng/L, P < 0.01, respectively]. There was significant difference among plasma NPY levels among the patients with mild, moderate, and severe PIH at admission (P < 0.01). At one week after delivery the concentrations of plasma NPY were significantly decreased in the moderate and severe subgroups compared with the value measured at admission (P < 0.01). Moreover, the NPY levels in patients with severe PIH after delivery were still higher than those of normal non pregnant women. CONCLUSIONS: The results suggested that the level of NPY in plasma is increased in women with PIH. Elevated plasma NPY levels may play a key role in the development of PIH. PMID- 11783362 TI - [The role of plasma placental isoferritin in pathogenesis of preeclampsia and its predictive value for preeclampsia]. AB - OBJECTIVE: To investigate the effect of placental isoferritin in pathogenesis of preeclampsia and its predictive value. METHODS: A prospective double-blinded study was performed. There were 120 initial normal pregnant women at earlier third trimester (from 24 to 34 weeks) in this study. Their plasma placental isoferritin and nitric oxide (NO) metabolites (nitrite/nitrate) (NO2-/NO3-) were examined by enzyme linked immunoabsorbent assay (ELISA) and Griess assay respectively. The outcomes of pregnancies were followed up. RESULTS: In 120 initial normal pregnant women, 19 pregnant women occurred preeclampsia (preeclampsia group), and 101 cases were normal (normal group) at follow up. The levels of plasma placental isoferritin (PLF) were significantly decreased in preeclampsia group (285.31 +/- 53.73 mg/L) than that of normal group (699.05 +/- 203.03) mg/L, P < 0.01. The levels of plasma NO were significantly increased in preeclampsia group (54.57 +/- 32.71 mumol/L) than that of normal group (38.89 +/- 30.00) mumol/L, P < 0.05. The significant negative correlation between the plasma placental isoferritin and NO levels was observed(r = 0.329, P < 0.01). At the cut point of 400 mg/L PLF level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index of PLF level predicting on the outcomes of pregnancy with preeclampsia were 100%, 85.15%, 55.88%, 100%, 0.645. CONCLUSIONS: The decrease of plasma placental isoferritin levels is associated with preeclampsia, and the endothelial cell damage may be one of its mechanism. The PLF may be an earlier predictor of preeclampsia at 24-34 gestational weeks. PMID- 11783363 TI - [The change of plasma von Willebrand factor and endothelin levels in patients with pregnancy induced hypertension]. AB - OBJECTIVE: To study the association of plasma von willebrand factor (vWF) and endothelin-1 (ET-1) levels in patients with pregnancy induced hypertension (PIH). METHODS: Plasma vWF and ET-1 were studied by ELISA method and immunoradiological method respectively in 36 patients with PIH, 18 normal pregnant women and 19 normal non-pregnant women. RESULTS: Circulation levels of vWF and ET-1 were increased with increasing severity of the PIH. In mild PIH patients, the levels of plasma vWF [(135.9 +/- 30.9)%, (P > 0.05)] weren't significantly higher than those in healthy pregnant women [(131.6 +/- 39.2)%, (P > 0.05)], but the levels of ET-1 [(63.7 +/- 4.8) pg/L] were significantly higher than those in healthy pregnant women [(47.1 +/- 4.7) pg/L, (P < 0.01)]. There were significant differences between groups of moderate-severe PIH [vWF (174.4 +/- 35.4)%, ET-1 (92.6 +/- 19.1) pg/L]. There was a positive correlation between the plasma vWF level and ET-1 level. CONCLUSION: The results suggested that plasma vWF and ET-1 concentration could be used as indicators for the severity of PIH. PMID- 11783364 TI - [The effect of human follicular fluid on mouse embryo culture]. AB - OBJECTIVE: To evaluate the effect of human follicular fluid (HFF) on mouse embryo culture. METHODS: Compare the effects of HFF and serum as a protein supplement on the in vitro development of mouse embryos. Measure the concentration of the epidermal growth factor (EGF) in HFF and human serum. RESULTS: HFF significantly enhanced the developmental potential of mouse embryos in vitro, even in the presence of meiotic inhibitors. HFF significantly increased frequency of development from the 2-cell stage to the 8-cell stage (72.9%), blastocyst stage (50.9%) and hatching (26.3%), compared with human serum(48.0%, 24.5%, 6.9%, P < 0.05). There was higher concentration of EGF with an average of 0.50 microgram/L in HFF group compared with human serum (0.26 microgram/L, P < 0.05). CONCLUSION: Human follicular fluid is effective in increasing the developmental potential of mouse embryos in vitro. PMID- 11783365 TI - [Effects of mifepristone on expression of estrogen receptor and progesterone receptor in cultured human eutopic and ectopic endometria]. AB - OBJECTIVE: To investigate the effects of mifepristone on expression of estrogen receptor (ER) and progesterone receptor (PR) in cultured human eutopic and ectopic endometria. METHODS: Endometrial (n = 22) and endometriotic (n = 12) tissues, obtained from patients with endometriosis, were cultured with and without mifepristone (1 x 10(-6) mol/L, 1 x 10(-4) mol/L) for 7-10 days. The expressions of ER, PR were determined by semi-quantitative immunocytochemistry method. Thirteen normal endometrial samples served as controls. RESULTS: The expressions of ER and PR in normal and eutopic endometrial cells showed the same cyclic pattern. The only difference was the significantly higher PR glandular content in eutopic endometria of endometriosis patients, as compared with normal controls [histochemistry score (H-score) 2.77 +/- 0.32 Vs 2.20 +/- 0.26 P < 0.05]. On the contrary, the ER, PR expressions in ectopic endometrial cells were significantly lower only during the proliferative phase (ER: gland 0.65-2.17 Vs 1.50-3.23, stroma 0.45-1.03 Vs 0.80-1.96; PR: gland 0.55-1.77 Vs 1.55-3.34, stroma 0.40-1.27 Vs 0.98-2.50; P < 0.05-0.01); significantly higher only during the late secretory phase (ER: gland 3.27 +/- 0.31 Vs 0.28 +/- 0.11, stroma 1.87 +/- 0.31 Vs 0.26 +/- 0.15; PR: gland 3.33 +/- 0.23 Vs 0.36 +/- 0.23) as compared with those of eutopic endometria. 10(-6)-10(-4) mol/L of mifepristone significantly suppressed the expressions of ER, PR in both eutopic and ectopic endometrial cells of endometriosis patients (P < 0.01) in a dose-dependent manner. CONCLUSIONS: Expression of ER, PR of endometriotic cells differed significantly from that of endometrial cells of patients with or without endometriosis. The down-regulatory effect on ER and PR may be one of the therapeutic mechanism of mifepristone on endometriosis. PMID- 11783366 TI - [A prospective, randomized controlled study comparing the effects of gonadotropin releasing hormone agonist long and short protocols for in vitro fertilization]. AB - OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH a) long and short protocols as part of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. METHODS: One hundred and nine infertile couples accepted a prospective, randomized comparative study for IVF or ICSI treatment were divided into GnRH-a long protocol group (55 cases) and GnRH-a short protocol group (54 cases). GnRH-a long protocol group: GnRH-a was taken by nasal spray 0.9 mg/day starting on day 21 of the previous menstrual cycle. Once the patient was down regulated, gonadotropin (Gn) injection was started. GnRH-a short protocol group: GnRH-a was taken by nasal spray 0.45 mg/day starting on day 2 of the menstrual cycle, and Gn was started on the same day. Two groups had human chorionic gonadotrophin (hCG) administered when the leading follicle was at least 18 mm in diameter. Oocytes were retrieved 36 hours after hCG administration guided by transvaginal ultrasounography. IVF/ICSI were performed as routine. RESULTS: Serum follicle stimulating hormone and luteinizing hormone (LH) levels on the day of starting Gn were lower in the long protocol group comparing with the short protocol group [(4.4 +/- 1.2) IU/L Vs (6.3 +/- 1.7) IU/L, (2.7 +/- 1.5) IU/L Vs (4.4 +/- 2.8) IU/L, P < 0.01 respectively]. The levels of serum estradiol (E2), LH and E2 per oocyte on the day of hCG injection were lower in the long protocol group comparing with the short protocol group [(7,119 +/- 3,584) pmol/L Vs (9,523 +/- 3,587) pmol/L, (1.0 +/- 1.0) IU/L Vs (4.0 +/- 3.4) IU/L, (610 +/- 315) pmol/L Vs (935 +/- 450) pmol/L, P < 0.01 respectively]. Patients treated with short protocol were stimulated for a shorter period, required fewer Gn ampoules than the long protocol group [(10.1 +/- 1.5) d Vs (11.1 +/- 1.2) d, (23.4 +/- 8.7) Amps Vs (28.0 +/- 8.6) Amps, P < 0.01 respectly]. There are no statistically differences between the two groups in the numbers of oocytes retrieved, metaphase of second meiosis oocytes, fertilized oocytes, cleaved embryos, high quality embryos and pregnancy rates. CONCLUSIONS: The GnRH-a long and short protocols have equal effects on controlled ovarian hyperstimulation for in vitro fertilization. Patients who received GnRH-a short protocol required fewer ampoules of gonadotrpins and shorter period of treatment than those who received the GnRH-a long protocol. PMID- 11783367 TI - [The effect of tamoxifen of endometrium]. AB - OBJECTIVE: To evaluate the effect of tamoxifen on the endometrium. METHODS: Hysteroscopy and endometrial biopsies were performed in 26 patients with breast cancer receiving tamoxifen and having vaginal bleeding or endometrial thickness detected by ultrasound. In addition 78 women with postmenopausal bleeding without receiving tamoxifen underwent the same examination. RESULTS: Thirteen (50.0%) patients receiving tamoxifen had endometrial or endocervical polyps, whereas 14 cases(17.9%) not receiving tamoxifen developed the polyps (P < 0.05). Nine (34.6%) patients receiving tamoxifen had thyperplasias, which was significantly higher than that of women not receiving tamoxifen (P < 0.05). CONCLUSIONS: The incidence of endometria disease in the patient with breast cancer receiving tamoxifen was increased. These patients should be closely monitored by transvaginal sonography and hysteroscopy. PMID- 11783368 TI - [Gene transfer of CD80 into a human ovarian cancer cell line and induction of cytotoxic T lymphocyte in vitro]. AB - OBJECTIVE: To investigate the proliferation and cytotoxicity of cytotoxic T lymphocyte (CTL) induced by ovarian cancer cells transfected with a CD80 gene containing retroviral vector. METHODS: The ovarian cancer cell line TYK cells were transfected with retro-virus vector PLXSN-hCD80. After geneticin (G418) selection, the CD80 expression of the transfectants was confirmed by flow cytometry. CTL was induced by co-culture of CD80-expressing TYK cells (TYK-hCD80) and peripheral-blood mononuclear cells (PBMC) in the presence of anti-CD3 monoclonal antibody (McAb). Proliferation of PBMC was measured using 3H-Thymidine incorporation assay. The lysis activity of CTL toward tumor cells was determined using methyl thiazolyl tetrazolium (MTT) assay. RESULTS: After transfection and G418 selection, the CD80 expression was proved by flow cytometry. The highest rate of CD80 expression was 84.9%. The TYK cell line expressing high CD80 was named TYK-hCD80. In the presence of anti-CD3 McAb, TYK-hCD80 significantly enhanced proliferation of PBMC than TYK cells (3H-Thymidine incorporation, (40,604 +/- 842) vs (8,000 +/- 594) cpm (P < 0.05). The lysis activity of CTL activated by TYK-hCD80 was higher than that of TYK(P < 0.05). CONCLUSIONS: Ovarian cancer cells expressing CD80 can induce the production of CTLs which have high lysis activity and high proliferation rate in the presence of anti-CD3 McAb. This study may provide the experimental basis for immunogenic therapy of ovarian cancer. PMID- 11783369 TI - [Phosphorylation of gap junction gene connexin 43 protein and dissociated calcium in HeLa cell line by all-trans-retinoic acid]. AB - OBJECTIVE: To investigate the regulation effect on signal transduction pathway of gap junction gene connexin (Cx)43 in human cervical carcinoma cell line HeLa by all-trans-retinoic acid(ATRA). METHODS: Cell culture, Fluo-3 AM loading and laser scanning confocal microscope, flowcytometer(FCM) and western blot were employed to detect expression and regulation effect on signal transduction pathway of gap junction gene connexin Cx43 in HeLa cells by retinotic acid(RA). RESULTS: After treated with ATRA, the intercellular second messenger dissociated calcium ([Ca2+]i) was much higher in HeLa cells (58.16 mumol/L) than untreated cell (35.73 mumol/L). A detectable and up-regulation of Cx43 of 43,000 protein in HeLa cells increased from 1.9% to 26.3% in RA-treated cells than untreated cell examined by FCM and western blot. Immunoblot analysis showed that only the treated cells had phosphorylated form of Cx43 protein. CONCLUSION: The anti-tumor effect of ATRA in HeLa cells might be due to up-regulation of Cx43 gene and its signal transduction pathway which medials gap junction intercellular communication. PMID- 11783371 TI - [Problems in connection with diagnosis and treatment of cervical lesions]. PMID- 11783370 TI - [A cross-sectional study on the promotion and execution of "the practiced guidelines for the management of common malignant gynecological tumors"]. AB - OBJECTIVE: To evaluate the promotion and execution of "the practice guidelines for the management of common malignant gynecological tumors (draft)" (guidelines). METHODS: Cross sectional study was applied. All obstetricians and gynecologists (Obs/Gyns) who attended the Chinese Medical Association's Senior Workshop for Department Chairmen of Obstetrics and Gynecology were included. RESULTS: Three hundred and fifty Obs/Gyns were inquired, while two hundred and eighty-one questionnaires were available. Ninety percent (253/281) of Obs/Gyns declared that they had read the guidelines, and 96.4% (271/281) of them thought it necessary to establish the guidelines. In those Obs/Gyns who read the guidelines, 87.7% (222/253) of them managed gynecological tumors according to the guidelines. In those who did not read the guidelines, most were obstetricians or worked in special hospitals, while all gynecological oncologists read the guidelines. In addition, there were still many suggestions on the guidelines. CONCLUSION: The guidelines has been playing a role in the management of common malignant gynecological tumors and need to be revised regularly. PMID- 11783372 TI - [Evaluation of cervical conization in diagnosis and management of cervical intraepithelial neoplasia]. AB - OBJECTIVE: To determine whether cervical conization can be instead of colposcopic multiple biopsies and to evaluate the clinical value of cervical conization in diagnosis and management of cervical intraepithelial neoplasia. METHODS: Fifty four patients with cervical intraepithelial neoplasia (CIN) diagnosed and treated at Peking Union Medical College hospital were retrospectively analyzed focusing on the comparative study in pathology between cerical conization and colposcopic multiple biopsies. RESULTS: Of the 54 patients, there was a correlation in pathology between cervical conization and colposcopic multiple biopsies in 22 cases (40.7%), but there was not much correspondence between cervical conization and colposcopic multiple biopsies in 32 cases (59.3%). In 31 cases conization performed for ruling out invasive cancer, there was a correlation in pathology between cervical conization and colposcopic multiple biopsies in only 13 cases (41.9%). After conization radical hysterectomy was performed in 2 cases (3.7%) because of early invasive carcinoma and simple hysterectomy was performed in 13 cases (24.1%) because of CINIII involved the gland and microinvasive carcinoma of the cervix. 39 cases (73.2%) were closely followed-up postoperatively with preservation of fertility. During the mean follow-up time of 18.3 months, no cytology abnormality was detected and 3 patients had pregnancy and delivery. Postoperative hemorrhage was main side effect for conization. CONCLUSIONS: Cervical conization plays a very important role in diagnosis and treatment of CIN and it can not be instead of colposcopic multiple biopsies. Cervical conization is a good choice for patient with CINIII and desired childbearing. PMID- 11783373 TI - [Study on nuclear DNA content and image cytometry in cervical cancer and precursor lesions]. AB - OBJECTIVE: The aim of this research was to study the biological and clinical features of cervical cancer and precursor lesions. METHODS: Nuclear DNA was analyzed by image cytometry (ICM) in 125 embedded tissue 5 microns sections stained with Feulgen stain. Samples included normal cervical squamous epithelium (n = 11), cervical intraepithelial neoplasia I (CIN I) (n = 22), CINII (n = 17) and CINIII (n = 13), cervical neoplasm (n = 62). RESULTS: The mean DNA content, nuclear area increased progressively from normal cervical epithelium, CINI, CINII, CINIII to invasive squamous carcinoma. Statistical analysis revealed significant difference (P < 0.05, < 0.01). Histograms of cellular DNA ploidy distribution showed different pattern, where 9 components (9C) cells were observed in cervical cancer and CINIII. No differences in DNA mean ploidy (DMP), DNA index (DI) and nuclear area were observed between cervical neoplasm. CONCLUSIONS: It is increased progressively from normal cervical epithelium to cancer, in which CINIII is turning point. PMID- 11783374 TI - [Loop electrosurgical excision procedure: a valuable method for the treatment of cervical intraepithelial neoplasia]. AB - OBJECTIVE: To determine the effectiveness and safety of loop electrosurgical excision procedure (LEEP) for the management of cervical intraepithelial neoplasia (CIN) and the significance of positive margins in cervical cone biopsy specimens with the relationship of prognosis. METHODS: LEEP under local anesthesia and colposcopic guidance was performed in an outpatient of colposcopic clinic. Records of 135 patients treated between Feb 1992 and Jul 1999 were reviewed prospectively. RESULTS: The median age of patients in this study was 42 years (range 18-67 years), parity 2.2 times (range 0-8 times). High-grade squamous intraepithelial lesion (HGSIL) accounted for majority of diagnosis according to pap smear (65.9%) and colposcopy (75.6%) respectively. The results of LEEP demonstrated negative histology in 7 patients (5.2%), human papilloma virus (HPV) infection in 2 patients (1.5%), CINI in 15 patients (11.1%), HGSIL in 108 patients (80.0%) which including 20 patients (14.8%) of CINII, 88 patients (65.2%) of CINIII, microinvasion in 3 patients (2.2%). Clear resection margin of lesion in cervix was noted in 78 (57.8%) patients. Unclear margins were appeared in 57 (42.2%) patients including 21 cases (15.6%) of resection margin positive and 36 cases(26.7%) of resection margin undetermined. HGSIL accounted for the majority (54 cases, 94.7%) in this kind of patients. The residual CIN occurred in 1 patient (4.8%) with the resection margin positive and 3 patients(8.3%) with the resection margin undetermined respectively. In 2 patients (2.6%) with the resection margin clear. Recurrence CIN occurred in 1 patient (4.8%) with the resection margin positive and 2 patients (5.6%) with the resection margin undetermined respectively, none of the patients (0.0%) with the resection margin clear. The overall cure rate in this study was 93.3% after first LEEP done. The residual CIN was identified in 6 (4.4%) patients. The recurrence CIN occurred in 3 (2.2%) patients. Complications of LEEP occurred in 14.1% (19/135) patients in this study. CONCLUSIONS: LEEP is a kind of effective and safe method for the treatment of cervical intraepithelial neoplasia. The status of resection margin should be concerned. Margin involvement of specimen is the risk factor for residual and recurrence of CIN. PMID- 11783375 TI - [Telomerase activity in cervical intraepithelial neoplasia]. AB - OBJECTIVE: To investigate the relationship between telomerase expression and the carcinogenesis of cervix, and the possibility of using telomerase as a marker to evaluate the natural history of cervical intraepithelial neoplasia (CIN). METHODS: Use the telomere repeat amplification protocol (TRAP) assay to detect cervical lesion in cervical scraping samples and cervical biopsy tissues. RESULTS: Sixty two point five percent, 60.0 percent, 82.4 percent and 61.9 percent cervical scraping samples exhibited telomerase activity in CINI, CINII, CINIII and cervical cancer, respectively, compared 50.0 percent, 45.0 percent, 96.4 percent and 95.2 percent in cervical biopsy tissue. In contrast, 20.0 percent and 26.7 percent in cervical scraping samples and cervical biopsy tissues of normal cervix. With the development of cervical lesion, the expression of tolemerase activation was increasing (P < 0.05). There was no significant difference between CINI and CINII (P > 0.05). There were significant differences between CINIII and CINI, CINII (P < 0.05) Telomerase activity was coincidence between the cervical scraping samples and cervical biopsy tissues. CONCLUSIONS: These results seem to suggest that the Telomerase expression may associate with the carcinogenesis of cervix. The telomerase activity assay of cervical scraping sample could be used as a marker to monitor and predicate the transit of CIN in clinical practice. PMID- 11783376 TI - [Video colposcopy in diagnosis of cervical squamous intraepithelial lesions]. AB - OBJECTIVE: To study the accuracy and efficiency of video colposcopy in diagnosis of cervical squamous intraepithelial lesions and clinical significance of seven colposcopic signs. METHODS: Two hundred and seventy-five patients with an abnormal cervical smear or vulva condyloma acuminata were re-evaluated by video colposcopy. 265 cervical biopsies performed under the guidance of video colposcopy for pathological study, as well 8 endocervical curettage (ECC) and 237 loop electrosurgical excision procedure (LEEP). RESULTS: The sensitivity, specificity and positive rate of video colposcopy in evaluation of cervical squamous intraepithelial lesions were 95.9%, 77.7%, and 84.5%. Video colposcopy diagnostic accuracy was 93.8% tally with the pathological results in observing normal transformation zone. False negative rate was 6.1%. 76.2% of cases with subclinical papillomavirus infection by acetowhite epithelium, while false negative rate was 23.7%. Twin signs, triple signs and cervical carcinoma were 100.0% tallying with the diagnosis of cervical lesions. CONCLUSIONS: Video colposcopy can be a very accurate diagnostic method in clinical practice. It is quite sensitive in diagnosis of severe cervical lesions. However, there was a relative high false negative rate in diagnosing mild cervical lesions. PMID- 11783377 TI - [Study on effect of delivery way on thyrotropin levels in pregnant women and their newborns]. AB - OBJECTIVE: To investigate the effect on thyrotropin (TSH) levels of pregnant women and their newborns in different delivery ways. METHODS: The serum TSH levels of 213 pregnant women and the umbilical cord blood TSH levels of their newborns (140 cases from normal vaginal delivery, 38 cases from cesarean section, 35 cases from low forceps delivery) were tested by immunoradiometric assay. Urinary iodine was detected from pregnant women before delivery. RESULTS: In pregnant women, the mean serum level of TSH in the forceps group [(4.13 +/- 0.69) mU/L] was significantly higher than those of the normal birth group [(2.58 +/- 0.87) mU/L, P < 0.01] and the cesarean section group [(2.81 +/- 0.45) mU/L, P < 0.01]. There was no difference in TSH level between the normal birth group and the cesarean section group. In newborns, the mean TSH level in the forceps group [(8.85 +/- 2.48) mU/L] was significantly higher than those of the normal birth group [(5.36 +/- 2.23) mU/L, P < 0.01] and the cesarean section group [(3.84 +/- 2.16) mU/L, P < 0.01]. The mean TSH level in the normal birth group was significantly higher than that of the cesarean section group (P < 0.05). The serum TSH levels of pregnant women were positively correlated with the umbilical cord blood TSH levels of their newborns in three groups. CONCLUSIONS: The contraction of uterus is the stimulus for the surge in TSH levels of pregnant women and their newborns after delivery. It's reliable that the TSH levels of newborns could be evaluated by monitoring the TSH levels of pregnant woman. PMID- 11783378 TI - [Clinical assessment of the effect of intravenous patient controlled intravenous analgesia and epidural patient controlled epidural analgesia in postoperative analgesia]. AB - OBJECTIVE: To compare the clinical effect and side-effect of intravenous patient controlled intravenous analgesia (PCIA) with patient controlled epidural analgesia (PCEA). METHODS: Two hundred and forty postoperative patients, who were randomly divided into three groups: group PCIA, group PCEA and control, 80 cases for each group, and the recovery of bowel movement, urinary retention, nausea, vomiting, pruritus, respiratory depression, postpartum hemorrhage, lactation and recovery of uterus were observed after operation. RESULTS: Overall patients in two PCA groups were satisfied with the postoperative analgesia. The incidence of urinary retention in group PCIA were significantly lower than that in group PCEA(P < 0.05). The recovery of bowel movement in group PCEA (17.51 +/- 10.33) was much bigger than that in group PCIA (28.70 +/- 16.36) (P < 0.05). There were no remarkable differences between two PCA groups in nausea, vomiting, respiratory depression and pruritus (P > 0.05). There were no remarkable differences between two PCA groups and control in the incidence of postpartum hemorrhage, lactation and recovery of uterus. CONCLUSIONS: Both PCIA and PCEA have excellent analgesic effect. PCIA has lower incidence of urinary retention, and has higher sedative incidence compared with PCEA. PMID- 11783379 TI - [Study on the relationship between leptin and neonatal weight and the expression of leptin in placenta]. AB - OBJECTIVE: To investigate the relationship between the leptin level and neonatal weight and the expression of leptin in placenta. METHODS: The concentrations of leptin in 100 maternal blood and umbilical blood of the term pregnant women were examined by radioimmunoassay (RIA). According to the neonatal weight to divide into the large for gestational age (LGA) group 19 cases, the appropriate for gestational age (AGA) group 65 cases, the small for gestational age (SGA) 16 cases. The level of leptin mRNA in 41 placental tissue was examined by Reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The expression level of leptin mRNA in placenta was 0.97 +/- 0.04, which was positively related to the neonatal weight significantly (r = 0.43, P < 0.01). The expression level of the LGA group (1.01 +/- 0.03) was significantly higher than the AGA group (0.97 +/- 0.02), (P < 0.01). The expression level of the SGA group (0.93 +/- 0.03) was significantly lower than AGA group, (P < 0.01). (2) The concentration of leptin in maternal blood was (14.22 +/- 7.66) micrograms/L, which was not related to the neonatal weight (r = 0.11, P > 0.05). (3) The concentration of leptin in umbilical blood was (7.58 +/- 5.15) micrograms/L, which was positively related to the neonatal weight (r = 0.57, P < 0.01). The concentration of leptin of LGA group was significantly higher than that of AGA group, which was (7.40 +/- 4.45) micrograms/L (P < 0.01). The concentration of leptin of SGA group was (2.79 +/- 1.54) micrograms/L, significantly lower than that of AGA group, (P < 0.01). CONCLUSIONS: The level of leptin in umbilical blood and placenta is closely related to the growth state of fetus. The level of leptin in maternal blood is not related to the neonatal weight. The placenta of pregnant woman is an important resource of leptin. PMID- 11783380 TI - [Analysis of factors influencing the clinical in a frozen thawed embryo transfer program]. AB - OBJECTIVE: To analyze the factors influencing the outcome in a frozen thawed embryo transfer (FTET) program. METHODS: Sixty FTET cycles performed in 53 cases from September 1997 to May 2000 were analyzed retrospectively. The related parameters were compared between the conceived and non-conceived cycles. RESULTS: One hundred and seventy eight out of 252 thawed embryos were survival. Embryo transfers were undergone in 57 cycles (53 patients), resulting in 17 pregnancies (30% per transfer or 28% per thawed cycle). There were no significant difference between conceived and non-conceived cycles in terms of the controlled ovarian hyperstimulation protocols, numbers of developed follicle and oocyte retrieved, fertilization rate, numbers of frozen embryo and the luteinizing hormone, estradiol, progesterone levels on human chorionic gonadotropin triggering day. The percentage of good quality embryo before freezing and after thawing and survival thawed embryos were higher in conceived cycles than those in non conceived cycles (83.8% Vs 60.7%, 76.8% Vs 50.0%, 82.4% Vs 66.3%, respectively P < 0.05). CONCLUSIONS: Good quality of frozen-thawed embryos and the trilaminar sonographic pattern of endometrium may be reliable predictors of success in pregnancy. PMID- 11783381 TI - [The study on human leucocyte antigen DQ region genes polymorphism in unexplained habitual abortion patients]. AB - OBJECTIVE: To investigate whether human leucocyte antigen DQ (HLA-DQ) genes polymorphism are related to the susceptibility to unexplained habitual abortion. METHODS: HLA-DQA1 and HLA-DQB1 gene typings are performed by polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP) technique in 32 cases of unexplained habitual abortion and 54 women with normal pregnancy history. RESULTS: In unexplained habitual abortion group, the frequency of DQB1 * 0604, 0605 allele is increased significantly compared with that of controls(12.5% and 2.8%, P < 0.05) and the frequency of DQB1 * 0501, 0502 allele is decreased significantly (3.1% and 11.1%, P < 0.05). The frequency of DQA1 alleles do not differ significantly between two groups. Furthermore, the frequency of DQA1 * 01/DQB1 * 0604,0605 haplotype in patients is significantly increased than that of controls (12.5% and 2.8%, P < 0.05). CONCLUSION: The results suggest that DQB1 * 0604,0605 allele and DQA1 * 01/DQB1 * 0604,0605 haplotype may be a susceptible gene and haplotype of unexplained habitual abortion, while DQB1 * 0501,0502 allele may be a protective factor for habitual abortion. PMID- 11783382 TI - [Effects of metformin on hyperinsulinemic anovulation]. AB - OBJECTIVE: To investigate the effects of metformin on serum testosterone (T) levels and ovulation in hyperinsulinemic women. METHODS: Twenty-nine patients with hyperinsulinemic anovulation were treated with metformin for 12 weeks. Among them 19 had history of clomiphene(CC) treatment with 11 cases failure. CC was given again after one month of metformin treatment. Serum T, luteinizing hormone, follicle-stimulating hormone, insulin(Ins) levels were measured after 4 weeks of treatment. Basic body temperature was also observed. RESULTS: Serum T and Ins levels declined significantly after 4 weeks of metformin treatment [(2.7 +/- 1.6) nmol/L Vs (1.9 +/- 1.0) nmol/L, (49.2 +/- 34.1) mU/L Vs (25.3 +/- 23.9) mU/L, P < 0.05, P < 0.05 respectively]. Eight cases ovulated spontaneously and 8 cases with history of CC failure became ovulatory during CC treatment. CONCLUSIONS: Metformin is effective for suppressing serum T levels and improving the outcome of ovulation. PMID- 11783383 TI - [Correlation of the metabolism of oxygen free radical in ovary, uterine muscle and vein blood with the pathogenesis of endometriosis or endometrioma]. AB - OBJECTIVE: To investigate the correlation of metabolism disturbance of oxygen free radical (OFR) with endometriosis and endometrioma, to provide an evidence for the diagnosis and treatment. METHODS: (1) The lipid peroxide (LPO), selenium (Se), superoxide dismutase (SOD) and vitamin E (VE) levels were respectively in the vein blood, ovary tissue of the chocolate cyst wall and chocolate cyst fluid in 32 operated patients with endometriosis (endometriosis group). (2) The levels above were determined separately in 23 operated patients with endometrioma (endometrioma group) and 30 cases of hysteroma (control group). RESULTS: (1) The LPO levels in vein blood and ovary tissue of endometriosis group were (6.357 +/- 1.251) mumol/L and (3.735 +/- 1.546) nmol/g protein. Which significantly higher than those of control group (P < 0.01). On the other hand, the Se. SOD. VE levels in endometriosis group were significantly lower than those in control group (P < 0.01-< 0.05). (2) The LPO level in ovary chocolate cyst fluid was higher than that in vein blood itself and control group. (P < 0.01). (3) The LPO levels in vein blood and uterine muscle of endometrioma was (5.882 +/- 1.711) mumol/L and (2.937 +/- 1.577) nmol/g protein, they were higher-than these in control group (3.547 +/- 1.640) mumol/L, (1.754 +/- 0.833) nmol/g protein, (P < 0.01). While, the Se. VE. SOD level tween the SOD level in uterine muscle tissue of endometriomin vein blood is significantly higher than those in control group (P < 0.01). There is no difference bea and control group (P > 0.05). CONCLUSION: The endome triosis and endometrioma is related to the produce or metabolistic imbalance of oxygen free radical, and so to the increasing of lipid peroxide. PMID- 11783384 TI - [The role of CA125 in the differential diagnosis of primary ovarian carcinoma and metastatic ovarian carcinoma originated from the gastrointestinal tract]. AB - OBJECTIVE: To assess the role of CA125 monoclonal antibody in the differential diagnosis of primary ovarian carcinoma and metastatic ovarian carcinoma originated from the gastrointestinal tract. METHODS: Immunohistochemical study using CA125 monoclonal antibody was performed on 33 primary ovarian cancer and 50 metastatic ovarian cancer of gastrointestinal origin. RESULTS: The positivity of CA125 was 84.5% in 33 cases of primary ovarian carcinoma, while in 50 metastatic ovarian carcinoma cases, only 4.0% was CA125 positive. The positivity of CA125 was significantly higher in primary ovarian carcinoma than metastatic ovarian carcinoma (P < 0.001). CONCLUSION: CA125 monoclonal antibody is useful in the differential diagnosis of ovarian carcinoma. PMID- 11783385 TI - [Transcatheter arterial embolization in intractable postpartum hemorrhage]. AB - OBJECTIVE: To asses the value of transcatheter arterial embolization treatment in intractable postpartum hemorrhage. METHODS: Fourteen patients of postpartum hemorrhage failed to the drugs treatment were performed transcatheter arterial embolization (TAE). Superselective catheterization to the bilateral uterial arteries or anterior branches of internal iliac arteries was carried out after intubation to single-side femoral artery by Seldinger's technique. When the catheter tip was proved in right place by digital substraction angiography (DSA) techniques, antibiotic solution was poured into arteries and then the arterial embolization with gelfoam particles was followed. RESULTS: All the patients were performed TAE successfully. The duration of TAE was 30-50 minutes [mean (41.8 +/- 6.4) minutes]. Bleeding was found in DSA mostly as diffuse intrauterine flow outward sign from one side or both side of uterial artery branches. After one time of TAE, the vaginal bleeding of all patients was stopped in 3-10 minutes [mean (6.1 +/- 3.6) minutes]. The follow-up showed that all patients had normal menstrual periods in 2-60 months and no serious complications were found. CONCLUSION: With the characteristic of fast homeostasis and less complications, TAE was proved to be an effective method for intractable postpartum hemorrhage. PMID- 11783386 TI - [Incidence of pregnancy induced hypertension and the effects on mother and fetus in Shanghai during 1989-1998]. AB - OBJECTIVE: To investigate the incidence of pregnancy induced hypertension (PIH) in Shanghai during 1989-1998. METHODS: The data were analyzed retrospectively from three municipal general hospitals and five special hospitals obstetrics and gynecology. RESULTS: There were 158,790 deliveries in ten years. The total numbers of PIH were 8,852 cases. The incidence of PIH was 5.57%. The rate of mild, moderate and severe PIH was 55.83%, 29.39%, and 14.78% respectively. There were 114 cases (1.29%) complicated with eclampsia. The rate of cesarean section was 66.97% in PIH patients. The complications of PIH were as following: abruptio of Placenta 0.52%, heart failure 0.34%, renal failure 0.20%, DIC 0.07% hemolysis, elevated liver enzymes and low platelet count(HELLP) syndrome 0.03%, maternal death one case. There were 9,197 birth of 8,852 cases of PIH (twin 343 cases, triplets one cases). The perinatal death 66 occurred in cases (7.18@1000) in which fetal death 48 cases, stillbirth 12 and neonatal death 6. CONCLUSION: The incidence of PIH and the rate of perinatal infant death can be reduced by strengthen antenatal monitoring, prevention, early diagnosis and treatment of PIH. PMID- 11783387 TI - [Ultrasonic measurement of fetal liver length and its clinical significance]. AB - OBJECTIVE: To establish the normal growth velocity of fetal liver length and compare them with those of intrauterine growth retardation, pregnant diabetes and maternal-fetal blood types imcompatible. METHOD: Three hundred and five normal pregnant women and 24, 10, 16 pathological pregnant women of intrauterine growth retardation (IUGR), gestational diabetes and maternal-fetal blood types incompatible respectively had ultrasonographic measurement of fetal liver length at 18 to 42 weeks' gestation. RESULTS: Normal fetal liver length has a linear relation to gestational age, and showed a significantly rapid increase after 28th week with a growth rate of 1.76 mm per week, and 1.00 mm per week before 28th week (P < 0.05). The growth rate of IUGR group before and after therapy were 1.19 mm and 1.23 mm per week, significantly lower than those of normal group (P < 0.05). The growth rate of pregnant diabetes group before and after therapy were 1.63 mm and 1.63 mm per week, no statistical significance with normal group (P > 0.05). The growth rate of maternal-fetal blood types incompatible group before therapy was 1.98 mm, showed no difference with normal group (P > 0.05), but after therapy, the growth rate of fetal liver was 1.38 mm per week, significantly lower than normal group (P < 0.05). CONCLUSION: Dynamic measurement of fetal liver length can help us to understand whether the fetus grow well in uterus and whether the treatments are effective. PMID- 11783388 TI - [Role of vascular endothelial growth factor in the genesis of pregnancy induced hypertension and its relationship with nitric oxide]. AB - OBJECTIVE: To study the role of vascular endothelial growth factor in the genesis of pregnancy induced hypertension (PIH) and its relationship with nitric oxide. METHODS: Serum vascular endothelial growth factor(VEGF) levels in 41 women with PIH and 20 normal pregnant women were measured by enzyme linked immunosorbent assay. The concentrations of nitric oxide (NO) in placental tissues were assayed by nitrite reductase. RESULTS: (1) Serum levels of vascular endothelial growth factor VEGF in PIH group were significantly lower than those in normal pregnancy. There was no difference between the mild PIH and normal group in the concentrations of VEGF. VEGF levels in moderate (23.1 +/- 4.1) ng/L and severe PIH (14.8 +/- 3.9) ng/L were significantly lower than those in normal group (P < 0.01). (2) The concentrations of NO in placental tissues in PIH group were significantly lower than those in normal pregnancy (P < 0.01). There was no difference between the concentrations of NO in mild PIH and those in normal pregnancy (P > 0.05). NO levels in moderate PIH (9.1 +/- 2.1) mumol/g and severe PIH (5.6 +/- 1.8) mumol/g were significantly lower than those in control group. (3) The serum levels of VEGF positively correlated with the concentration of NO in placental tissues. (r = 0.65, P < 0.01). CONCLUSION: The serum levels of VEGF and the concentrations of NO in women with PIH are both suppressed. The changes of VEGF levels might play an important role in the pathogenesis of PIH. PMID- 11783389 TI - [Complications in laparoscopic gynecologic surgery: analysis of 34 cases]. AB - OBJECTIVE: To investigate retrospectively the complication rate of gynecological laparoscopies at Peking union medical college (PUMC) hospital over 6-year period. METHODS: 1,769 laparoscopic surgeries were carried out from Jan. 1994 through Oct. 1999. The procedures included 1,421 adnexal surgeries, 52 myomectomies and 296 laparoscopic assisted vaginal hysterectomy (LAVH). Complication was defined as an event that had modified the usual course of the procedure or of the postoperative period. RESULTS: Complications occurred in 34 cases, the overall complication rate was 1.9%. Unintended laparotomies occurred in 6 cases (0.3%). Complication rate was 0.9%, 1.9% and 6.8% in adnexal surgeries, myomectomies and LAVH respectively. 12 (35.3%) complications related to puncture and pneumoperitoneum, including five severe emphysema, 7 injuries to epigastric blood vessels of abdominal wall and omental blood vessel, this figure represented 35.3% of all complications of this series. 5 (14.7%) intraoperative, complications occurred during the laparoscopic surgery (3 severe bleedings, 1 bladder injury and 1 skin burn of leg related to the electrode plate), laparotomy was required in 4 of these cases. 17 (50.0%) complications occurred during postoperative stage: 2 intraperitoneal hemorrhages needing re-laparotomy, 2 bowel complications, 4 nerve paresis and 9 febrile morbidities. CONCLUSIONS: In our experience, operative gynecologic laparoscopy is associated with acceptable morbidity rate, but can not be overlooked. Complications seems related to advanced procedures such as LAVH. PMID- 11783390 TI - [Study on polymorphism of human leukocyte antigen I in patients with endometriosis]. AB - OBJECTIVE: To study the possibility of a correlation between polymorphism of human leukocyte antigen (HLA)-I antigen and occurrence of endometriosis (Em). METHODS: Polymorphism of HLA-I A and B locations were detected by mini lymphocytotoxin test in 40 surgically proven Em patients and 50 normal controls. The frequency of different antigens on both A and B sites were compared between the 2 groups. RESULTS: No significant difference of the antigen frequency at HLA I A site was shown between Em and control groups. However, at HLA-I B site, frequency of B46 antigen in Em group was significantly higher [33% Vs 16%, P < 0.05, relative risk (RR) 2.5278] and frequency of B48 antigen in Em group was significantly lower (3% Vs 16% P < 0.05, RR 0.1346) as compared with those of the controls. CONCLUSIONS: The occurrence of Em may be associated with the presence of HLA-I B46 antigen. On the contrary, the HLA-I B48 antigen might play a protective role against Em. PMID- 11783391 TI - [Retrospective analysis of endometrial neoplasms treated by different therapeutic modalities]. AB - OBJECTIVE: To compare the therapeutic effects of different remedies in patients with endometrial carcinoma. METHODS: Total of 386 patients with metracarcinoma underwent 3 different treatments: (1) operation only 145 cases; (2) operation and complemental radiotherapy 161 cases; (3) radiotherapy only 80 cases. Then they were followed up for 5 years and more. RESULTS: The 5-year survival rates of operation group were 78.9% (56/71), 61.0% (25/41) and 18.2% (6/33) in stage I, stage II, and stage III-IV respectively, for operation and complemental radiotherapy, they were 75.0% (33/44), 59.5% (44/74) and 48.8% (21/43), for radiotherapy, 34.8% (8/23), 18.8% (3/16) and 0.0% (0/41). There was no difference between operation group and operation plus radiotherapy in patients with stage I and stage II (P > 0.05). However the 5-year survival rates were significantly higher in operation plus complemental radiotherapy group and those only received operation in stage III stage IV patients (P < 0.001). And no matter in what stages, the therapeutic effect was worse in radiotherapy group than other two groups (P < 0.001). CONCLUSION: The remedies with operation as main measure are the best choice for metacarcinoma, radiotherapy merely is fit with those who can not be operated on. PMID- 11783392 TI - [Clinical analysis of 25 cases of leiomyoma of the vagina]. AB - OBJECTIVE: To study the histologic source, clinical features and treatment methods of leiomyoma of the vagina. METHODS: From January of 1988 to January of 1999, 25 patients with leiomyoma of the vagina were retrospectively analyzed. RESULTS: The clinical features of leiomyoma of the vagina were slow in growth and solitary in number. Leiomyoma of the vagina can be recurrence and sarcomatous change. The symptoms of leiomyoma of the vagina depended on the size and location of the leiomyoma. Treatment consisted of surgical excision by vagina. CONCLUSIONS: Leiomyoma of the vagina is a rare condition. Whenever such a tumor is detected, it has to be removed immediately to prevent further growing and sarcomatous change in the future. PMID- 11783393 TI - [Radiotherapy in the treatment of uterine sarcomas]. AB - OBJECTIVE: To study radiotherapy in the treatment of uterine sarcomas and response to radiation in primary or recurrent uterine sarcomas. METHODS: A total of 102 uterine sarcomas treated in the Cancer Hospital from May 1960 to June 1999. A retrospective review of 45 patients receiving surgery alone, 29 patients for postoperative radiotherapy, 4 radiotherapy alone, 24 recurrent sarcomas receiving radiotherapy. RESULTS: The 5-year overall survival for 45 patients treated with surgery alone and 29 patients managed by postoperative radiotherapy were 56.7% and 58.6% respectively (P > 0.05). The addition of radiotherapy significantly reduced the local recurrence rate from 42.2% to 20.7% (P < 0.05). The tumor was disappeared completely by treatment of radiotherapy alone in 3 patients of primary uterine cervix sarcomas. 1 patient was free of disease at 36 months. Other 2 patients died 9 and 11 months later because of distant metastases. The complete and partial response rate of radiotherapy was 50.0% for recurrent tumors. The radiotherapeutic sensibility of endometrial stromal sarcomas, mixed mesodermal sarcomas and leiomyosarcomas was downward tendency in turn. CONCLUSIONS: The postoperation adjuvant radiotherapy reduced the pelvic recurrent significantly. Radiotherapy should be used in the treatment of uterine sarcomas as an important part of combination therapy. PMID- 11783394 TI - [Effect of a risk of malignancy index in preoperative diagnosis of ovarian cancer]. AB - OBJECTIVE: To evaluate the ability of a risk of malignancy index (RMI), based on a serum CA125 level, ultrasound findings and menopausal status, to discriminate a benign from a malignant pelvic mass. METHODS: One hundred and forty women with a pelvic mass, 30 years or older, admitted between January 1998 and June 1999, were studied. The sensitivity, specificity and positive predictive value of serum CA125 level, ultrasound findings and the menopausal status separately and combined into the RMI, to diagnose ovarian cancer. RESULTS: RMI was more accurate than any individual criterion in diagnosing cancer. Using a RMI cut-off level of 200 to indicate malignancy, the RMI derived from this data set gave a sensitivity of 87.3%, specificity of 84.4%, and positive predictive value of 82.1%. CONCLUSIONS: RMI is able to correctly discriminate between malignant and benign pelvic mass. It can be introduced easily into clinical practice to facilitate the selection of patients for primary surgery. PMID- 11783395 TI - [Therapeutic effects of adenovirus-bcl-xs gene to the ascites tumor of nude mice model of human ovarian carcinoma]. AB - OBJECTIVE: To investigate the effects of adenovirus-bcl-xs gene on the ascites tumor growth inhibition and survival rate of nude mice with human ovarian carcinoma transplanted intraperitoneally. METHODS: Making an adenovirus-bcl-xs gene vector infected in JH293T cell and reproduced in it. After having detected the inhibitory potential of adenovirus-bcl-xs gene on NUTU-19 cell we use it to transfer intraperitoneally to ascites tumor model of human ovarian carcinoma transplanted in nude mice. Detected the ascites formation, the survival time and survival rate of nude mice with the human ascites tumour. The weight and toxic adverse systemically effects of nude mice was observed and morphology of adenovirus was observed by electromicroscope and the gene expression was detected by immunocell chemistry. RESULTS: The adenovirus-bcl-xs gene could reproduce in JH293T cell and had inhibitory potential on NUTU-19 cell, the survival time of nude mice was longer and the survival rate was higher, and the time of ascites formation was retarted. There was no obvious alternation in the weight and systemic toxic-adverse effects observed. CONCLUSIONS: The data suggests that the transfer of adenovirus-bcl-xs gene to the ascites tumour of nude mice with human ovarian carcinoma could improve the survival rate of nude mice and retard the time of ascites formation. It may be a useful method of gene therapy in the treatment of ovarian carcinoma. PMID- 11783396 TI - Evolution in health and disease: work in progress. AB - This article surveys progress in Darwinian medicine since 1991. Evolutionary thinking has been providing an increasing flow of fresh ideas into medical science, ideas that would not be suggested by other perspectives. Recent contributions have shed new light on the evolution of virulence, of antibiotic resistance, of oocytic atresia, of menopause, of the timing of the expression of genetic disease, of links between mate choice and disease resistance, and of genomic conflict between mother and fetus over resource provisioning. An important consequence of changes from the environment of evolutionary adaptedness concerns reproductive cancers; the incidence of reproductive cancers may be linked to changes in the frequency of menstruation in postindustrial societies. Other intriguing developments include some unanticipated and undesirable consequences of good hygiene, hope from an unexpected quarter for progress on nerve and muscle regeneration, evolutionary interpretations of mental disease, and insights from functional genomics into the nature of tradeoffs. The application of evolutionary thinking to problems in medical research and practice has thus yielded an abundant and growing harvest of insights. Some are well founded, others remain speculative. The field is moving from an initial phase dominated by speculation and hypothesis formation into a more rigorous phase of experimental testing of explicit alternatives. Currently the most promising areas, those in which experimental rigor can be applied efficiently, include experimental evolution and functional genomics. The pioneers can be proud of what they have set in motion. PMID- 11783397 TI - Evolution in changing environments: the "synthetic" work of Clausen, Keck, and Hiesey. AB - The studies of Clausen, Keck, and Hiesey (CKH) have been widely cited as exemplars of ecotypic differentiation in textbooks and in the primary literature. However, the scope of their findings and achievements is significantly greater than this. In this paper we analyze the research program of CKH, highlighting their major findings during the years when the modern synthesis of evolution was taking shape. That synthesis, curiously, drew little from their examples, although their studies at the Carnegie Institution represent conceptual and methodological work that is still relevant. The works of CKH not only embodied the principles of the nascent synthesis, but often provided needed supporting data. Their classic work, especially on Achillea and Potentilla, produced abundant evidence on population differentiation of many quantitative traits and plant phenotypes, as well as demonstrating the now commonly reported distinction between environmental and genetic determination of traits. Their ecological genetic investigations of quantitative traits in plants were in sharp contrast to contemporaneous animal studies on adaptation that focused on discrete polymorphisms--with correspondingly little influence of the environment on phenotypic expression. Of utmost importance was the demonstration by CKH of adaptive differentiation by natural selection and their approaches to understanding the genetic structure of populations. PMID- 11783398 TI - The hormetic zone: an ecological and evolutionary perspective based upon habitat characteristics and fitness selection. AB - Fitness varies nonlinearly with environmental variables such as temperature, water availability, and nutrition, with maximum fitness at intermediate levels between more stressful extremes. For environmental agents that are highly toxic at exposures that substantially exceed background levels, fitness is maximized at concentrations near zero--a phenomenon often referred to as hormesis. Two main components are suggested: (1) background hormesis, which derives from the direct adaptation of organisms to their habitats; and (2) stress-derived hormonesis, which derives from metabolic reserves that are maintained as an adaptation to environmental stresses through evolutionary time. These reserves provide protection from lesser correlated stresses. This article discusses illustrative examples, including ethanol and ionizing radiation, aimed at placing hormesis into an ecological and evolutionary context. A unifying approach comes from fitness-stress continua that underlie responses to abiotic variables, whereby selection for maximum metabolic efficiency and hence fitness in adaptation to habitats in nature underlies hormetic zones. Within this reductionist model, more specific metabolic mechanisms to explain hormesis are beginning to emerge, depending upon the agent and the taxon in question. Some limited research possibilities based upon this evolutionary perspective are indicated. PMID- 11783399 TI - [Neuroimmunology at the turn of the century: a prologue to the 21st century]. PMID- 11783400 TI - [Prognostic significance of early CT changes in ischemic stroke patients]. AB - The aim of the study was to establish the prognostic value of early CT findings in predicting the 30-day mortality after stroke, to assess the prevalence of these findings in acute stroke patients, and to examine the correlation between these findings and the clinical status. 134 patients (mean age 67.5 +/- 12.1) with supratentorial ischaemic stroke and CT performed within 12 hours from onset of the symptoms were included into the study. The neurological deficit and consciousness disturbances were assessed by means of Scandinavian Stroke Scale. The 30-day mortality was registered. CT findings were found in 84 (63.7%) patients, including hypodense lesions in 74 (55.5%), mass effect in 55 (41.0%) and hyperdense middle cerebral artery sign in 5 (3.7%) cases. Patients with mass effect had greater neurological deficit on admission (p < 0.0001), more frequently developed disorders consciousness (p = 0.001) and had greater 30-day mortality (p < 0.0001). Patients with hypodense lesions of at least two types presented with greater neurological deficit observed on the second day of hospitalization (p < 0.05) and had also greater 30-day mortality (p = 0.01). On multivariate analysis mass effect seen in early CT, as well as older age and greater neurological deficit appeared to be independent predictors of 30-day mortality. PMID- 11783401 TI - [Incidence of dementia in Parkinson disease]. AB - The aim of our study was to assess the frequency of dementia in a highly selected (according to diagnostic criteria of Parkinson's disease and other causes of dementia) group of patients. MATERIAL AND METHODS: 46 patients (F 18, M 28), mean age--63.9 (39-80) years, with good response to L-Dopa. Besides the neurological examination, all patients underwent CT and psychological tests (Wechsler Bellevue, Mini Mental and Hamilton test--to exclude severe depression as cognitive problem cause). In the group with dementia thyroxine and cholesterol tests and EEG were performed. RESULTS: Within the whole group the features of dementia (the index of deterioration in Wechsler test > 25% and/or 23 or less points in Mini-Mental) were recognized in 11 (23.9%) patients. In comparison to the rest of the patients, in the group with dementia the mean age was 8.1 years higher, mean age at onset of the disease was 6.4 years higher, mean time of the disease 1.5 years longer and the severity of the disease measured in Hoehn-Yahr rating scale was 0.76 points higher (2.20 vs 2.96). In the whole group severe depression (> 18 points in Hamilton test) was revealed in 6%, whereas moderate (8 17 points) occurred in 71%. CONCLUSIONS: Older age, later onset of symptoms and more advanced disease are the risk factors of dementia. Other causes--like dementia of Alzheimer's type may be suspected or two distinctive forms of Parkinson's Disease with and without dementia exist. PMID- 11783402 TI - [Chemokines MIP-1 and MCP-1 and patients with multiple sclerosis treated with interferon beta-1a]. AB - Chemokines: MCP-1 and MIP-1 alpha may play an important role in the pathogenesis of multiple sclerosis, influencing migration of lymphocytes to the CNS. One of possible mechanisms of interferon beta action may be an effect on chemokines. We measured MCP-1 and MIP-1 alpha chemokines in sera of 24 patients with MS treated with interferon beta-1a before and after 3 months of therapy and in 15 control patients. There was a significant increase of MIP-1 alpha concentration in sera of MS patients in comparison with control group. After 3 months of therapy with interferon beta-1a, MIP-1 alpha and MCP-1 levels did not differ from the values before therapy. Investigations will be continued after longer time of treatment with interferon beta. PMID- 11783403 TI - [EEG value in cases of epileptic seizures in early phase of stroke]. AB - The aim of our work was to assess the usefulness of EEG in patients with seizures in acute phase of stroke. EEG patterns of 54 patients with epileptic seizures at the onset of stroke were evaluated: 45 of ischaemic, 6 of haemorrhagic origin and 3 with lacunar stroke as confirmed by CT or MR examination. Out of 40 patients, who had a single or multiple seizures at the onset of stroke, EEG revealed focal slow waves in 90% and in 22.5% they were accompanied by interictal epileptiform discharges. None of those patients had recurrent seizures during the time of hospitalisation irrespectively of applying antiepileptic drugs. In the remaining 14 patients prolonged disturbances of consciousness were observed. EEG examination revealed simple partial status epilepticus (SE) in 10 and complex partial SE in 4 of them. In 11 of those patients EEG disclosed fragments of periodic lateralized epileptiform discharges (PLED) interrupted by seizure activity. The findings indicate that in patients with seizures in the acute phase of stroke EEG examination is very helpful in making the proper therapeutic decision by recognizing the SE. The introduction of antiepileptic drugs is generally not necessary in stroke patients with single seizures. PMID- 11783404 TI - [MRI in the diagnosis of congenital white matter diseases and other neurodegenerative diseases]. AB - The results of cranial magnetic resonance imaging in 76 children (aged 3 weeks- 17 years) with neurometabolic or other neurodegenerative diseases are presented. The number of diagnosed diseases was 22. MR symptomatology of 11 of them is presented. The list of characteristic images includes metachromatic leukodystrophy, mucopolysaccharidoses, X-linked adrenoleukodystrophy, Leigh, Menkes and Pelizaeus-Merzbacher diseases, glutaric aciduria type I, Canavan disease, neuronal ceroid lipofuscinosis, Hallervorden-Spatz and Huntington diseases. The diagnosis of neurometabolic/neurodegenerative diseases cannot be based on MRI alone but in some of them (metachromatic leukodystrophy, adrenoleukodystrophy, Leigh and Menkes diseases, glutaric aciduria type I, Canavan and Hallervorden-Spatz diseases) MRI can strongly suggest the diagnosis. PMID- 11783405 TI - [Dysontogenetic tumors of the vertebral column]. AB - 13 patients were managed surgically for dysontogenetic tumours of vertebral column between 1970 and 1997. 6 males and 7 females aged from 3 to 45 years (average age = 28.46 +/- SD 12.81 years). At the cranio-vertebral junction one tumour was localised. Other tumours were in different segments of vertebral column as follows: 3 cases in thoracic segment, 6--in lumbar and 2--in lumbo sacral region. X-ray examination revealed coexistence of dysraphic or other spinal defects in 10 cases. Surgery was carried out in all cases using various technique. Histological examination disclosed: epidermoid cyst 6, dermoid cyst 3 and teratoma 4. Good results of treatment were achieved in 11 patients, while in 2 cases neurological deficit symptoms were exacerbated. In patients after teratoma removal post-operative radiotherapy was indicated. PMID- 11783406 TI - [Surgery of multi-sutured craniosynostosis in childhood]. AB - According to own critical experience with the treatment of craniosynostoses (1954 81), using various methods from partial morcellement to total ablation of the cranial vault, the author applied (1982-2000) compound surgical decompression in 40 cases of turricephalic craniostenosis due to multisutural craniosynostosis. The surgical approach to the problem was supported by pre- and postoperative observations of computed three-dimensional bone reconstruction, furthermore by investigation of alterations of SPECT detecting the critical areas of most pronounced intracranial tightness of the skull leading to localized and general cerebral blood flow impairment of the developing brain. The application of newer diagnostic methods contributed to deeper understanding of mechanisms concerning neurodevelopmental retardation and behaviour or defect, disturbances as epilepsy, cranial nerve palsy, spastic paresis, hypothalamic-pituitary insufficiency or poor intelectual performance. This made the possible treatment of preoperative clinical symptoms more efficient. By an early operation we solve the disproportion between the too small skull volume limited by premature ossification of sutures which resulted previously in compression of the growing in size, of the maturing brain. In cases of more complex pathology orbitotomies, with a reconstructive advancement of the orbital rim and maxillas should be performed with multidisciplinary cooperation. PMID- 11783407 TI - [Functional magnetic resonance imaging in the assessment of motor centers in patients with brain tumors in motor area]. AB - Magnetic resonance imaging (MRI) is become recognised as the most sensitive and specific imaging modality for the examination of central nervous system pathology. Blood oxygen level-dependent (BOLD) contrast imaging is a non-invasive functional MRI technique for localising active neuronal brain centres. The aim of our study was to determine usefulness of fMRI in detecting hand movements cortical activity in hemisphere with brain tumour and comparison with corresponding one. Six right-handed patients with brain tumours of central sulcus area, aged 20-50 years were examined using a commercial 1.5 T scanner. All patients underwent both conventional and functional magnetic resonance imaging (MRI) examinations. Simple hand movements were examined separately for right and left hand at a self-paced rate. Significant increase of signal intensity was found in: a) contralateral primary motor cortex in all cases during both motor tasks, b) ipsilateral primary motor cortex, supplementary motor cortex and premotor cortex of both hemispheres in a part of the cases c) displacement of the activity in the affected hemisphere in comparison to the opposite one was noticeable depending on the localisation and size of the tumour and accompanied oedema. Usefulness of functional MRI in detecting primary motor area in patients with brain tumours was proved. There is a difference between activation in affected cortex and corresponding normal cortex in the opposite hemisphere. PMID- 11783409 TI - [The importance of brain stem evoked potentials in the diagnosis of neurosurgical patients]. AB - The technique of Brainstem Electric Response Audiometry (BERA) is a non-invasive electrophysiologic method used in comatose patients for localization of areas of neuronal and synaptic dysfunction not evident in clinical evaluation. This test has a diagnostic and prognostic value in detection of abnormalities and evaluation of comatose head-injured patients at a reversible clinical stage. In contrast to most clinical signs, brainstem auditory evoked potentials are independent of levels of consciousness, analgesics, sedatives. This test is aetiologically non-specific and must be carefully integrated into the clinical situation. Generators of brainstem auditory evoked potentials are located in the auditory nerve (waves I and II) and brainstem (waves III-V). Patients in acute posttraumatic coma are assessed by means of Glasgow Coma Score (GCS), which is reliable in forecasting a favourable outcome. Patients with a score 8 points have an unfavourable outcome in 16%. Brainstem auditory evoked potentials are reliable predictors of unfavourable outcome. Subsequent brainstem auditory evoked potential testing provides relevant prognostic information, since improvement of graded brainstem auditory evoked potentials indicates a favourable outcome. Progressive deterioration of brainstem auditory evoked potentials indicates irreversible damage and is associated with unfavourable outcome, whereas singular abnormal evoked potentials may result from reversible neuronal dysfunction. The absence of waves III-V associated with the end EEG activity is the proof of brain death. Serial BERA monitoring has been used to evaluate progressive clinical syndromes, such as "uncal herniation" and evolving brain death. The use of serial BERA recordings appeared to improve the outcome predictions in comparison with single BERA tests. A combination of brainstem auditory evoked potentials, somatosensory and visual evoked potentials (multimodality evoked potentials-MEP) provides more information for management of a patient than a single evoked potential modality. The main goal to use BERA is early detection of secondary deterioration in comatose patients suffering from intracranial lesions. The results of brainstem auditory evoked potentials and clinical examination of patients obtained within the acute phase after head injury may indicate increased intracranial pressure (ICP) and incipient transtentorial herniation but do not always predict outcome (GOS). The outcome can be better evaluated later, 3-6 days after head injury. In summary, BERA is a non-invasive, safe and objective method of evaluating patients after severe head injury and adds valuable information for assessment of their outcome. PMID- 11783408 TI - [The role of tumor infiltrating lymphocytes in the immunopathology of gliomas]. AB - Immune response was studied to human glioblastoma with an accumulation of lymphocytes at the tumour site. The anti-tumour activity of the tumour infiltrating lymphocytes was confirmed by results from numerous investigations. The role of lymphocytes in gliomas is still widely discussed. Recent studies suggest a potential role of infiltrating lymphocytes as cellular effectors of angiogenesis. In this paper the authors discuss the immune response abnormalities especially with regard to the role of lymphocytes in angiogenesis. PMID- 11783410 TI - [Pathomechanism and clinical presentation of neurobehavioral disturbances in a patient with MELAS syndrome]. AB - The authors present the results of a longitudinal study of the neurobehavioral disturbances seen in K.S., a 22-year-old female patient with a mitochondrial cytopathy (MELAS) caused by the novel mutation C8293T. K.S. became ill in 1994 at the age of 16. She was referred for diagnosis to several different clinics. Four years after onset, the clinical diagnosis was established in the Department of Medical Rehabilitation at the Cracow Rehabilitation Center; the diagnosis was not confirmed until six years after onset, following the discovery of the mutation in the patient's mtDNA at Columbia University. Since 1996 the patient has presented with progressive dementia and periodic stroke-like episodes that produced fluctuating neurological symptoms. The essential pathomechanism of the neurobehavioral disturbances consists in the fragmentation of complex cerebral processes into their constituent elements; individual functions are frequently correctly executed on a lower level of cerebral organization, but the patient is unable to combine them into a sensible whole. The authors discuss the theoretical and clinical significance of the results presented here. PMID- 11783411 TI - [Brain stem syndrome after cervical chiropractic manipulations]. AB - This is a case report of a 41-year old man who had ischaemic lesion in the pons following chiropractic manipulation. He had brainstem syndrome with right hemiparesis. He improved. After 4 a year follow-up he is in a very good condition. PMID- 11783412 TI - [Selective mechanical dilatation of brain arteries: intracranial angioplasty]. AB - Intracranial vascular stenosis of haemodynamic significance is underappreciated both clinically and diagnostically. It is thought to be the cause of cerebral ischaemia in 8% of patients. Now it is possible to perform dilatation of the intracranial arterial stenosis by modern intraarterial angioplasty. Two cases are presented of successful dilatation of middle cerebral artery trunk stenosis. Diagnostic problems, follow up and pharmacological treatment as well as technique of intravascular treatment is described. PMID- 11783413 TI - [Spontaneous spinal epidural hematoma. Report of two cases]. AB - In the paper 2 cases of non-traumatic spinal epidural haematomas are presented. The possible aetiological factors--vascular malformation, coagulopathy, anticoagulants and neoplasm are discussed. Neurological state, diagnostic procedure and treatment are described. Taking into account our experience we state that only early diagnosis and operation-surgical decompression of spinal cord, could result in complete recovery. PMID- 11783415 TI - [Intracranial dissemination as the first important clinical sign of thoracic cord ependymoma in a boy aged 8]. AB - This paper reports a case of the rare entity of a cerebral metastasizing ependymoma of the thoracic spinal cord in a 8 year old boy. PMID- 11783414 TI - [Pituitary adenoma penetrating the sphenoidal sinus and nasal cavity: a case report]. AB - We describe a case of pituitary adenoma penetrating to the sphenoidal sinus and nasal cavity in a patient with recurrent nasal polyps. Histopathological examination of the removed polyps revealed transitional carcinoma. CT and MRI of the head showed a solid tumour filling the spheniodal sinus and the sella, penetrating to posterior ethmoid cells and superior nasal duct. In hormonal investigations increased concentration of prolactin (PRL) was found. Histopathological examination performed after neurosurgical operation revealed pituitary adenoma, and the diagnosis of pituitary adenoma was established. About 30% of tumour cells gave positive reaction with anti-PRL antibody in the immunocytochemical investigation. The immunocytochemical investigation of the nasal polips was also done--similarly about 30% of cells showed strong positive reaction with anti-PRL antibody. The investigations indicate the presence of pituitary macroadenoma (prolactinoma), manifesting initially as nose tumour. Considering cases of ectopic pituitary adenomas covered with transitional epithelium (for example some nasal tumours and paranasal sinuses tumours) immunocytochemical investigations are recommended in such cases. PMID- 11783416 TI - [Paranoid syndrome in a patient with tumor in anterior part of corpus callosum. Case report]. AB - The reported case was a patient with tumour situated in the region of the corpus callosum, with symptoms diagnosed initially as affective syndrome and later on as paranoid syndrome. With this diagnosis he was treated for 12 years in psychiatric out-patient clinics and hospitals with antidepressants and and neuroleptics. Brain imaging (CT and MRI) performed only after an epileptic seizure demonstrated a tumour in the anterior part of the corpus callosum with a broad oedema area. Neuropsychological examination revealed disturbances of emotional-motivation processes and defects in cognitive functions. Following surgical treatment only a slight improvement of functioning was noted. Histological diagnosis (PNET) suggested that the tumour was expanding during many years. Much earlier diagnosis with neurosurgical intervention could result in a better therapeutic effect. PMID- 11783417 TI - Molecular aging. PMID- 11783418 TI - Vascular viewpoint. A systematic review of intra-arterial thrombolytic therapy for lower-limb ischemia. PMID- 11783419 TI - Abstracts of the 10th European Workshop on Neonatology. Toledo, October 25-27, 2001. PMID- 11783421 TI - [Education in Biological Sciences: it demands urgent changes]. PMID- 11783423 TI - Lung cancer incidence in the world. PMID- 11783424 TI - Genotyping and drug response: use of single nucleotide polymorphisms (SNPs) versus haplotypes to predict albuterol efficacy. PMID- 11783425 TI - UGT1A1 polymorphism predicts irinotecan toxicity: evolving proof. PMID- 11783426 TI - The MDR1 C3435T polymorphism: effects on P-glycoprotein expression/function and clinical significance. PMID- 11783427 TI - Are certain genetic patterns more common in persons with irritant contact dermatitis? A study in metal worker trainees. PMID- 11783428 TI - Effect of patch test type on irritation potential. PMID- 11783429 TI - Orally elicited allergic contact dermatitis to tetraethylthiuramdisulfide. PMID- 11783430 TI - Occupational photoallergic contact dermatitis to olaquindox. PMID- 11783431 TI - Relaxer-induced alopecia. PMID- 11783432 TI - Abstracts of the 53rd Annual Conference of the Cardiological Society of India. December 6-9, 2001, Hyderabad. PMID- 11783433 TI - A growing set of platelet-activating bacterial proteins. PMID- 11783434 TI - Terminal plasmocytoid differentiation of malignant B cells induced by autotumor reactive CD4(+) T cells in one case of splenic marginal zone B-cell lymphoma. PMID- 11783435 TI - Cytomegalovirus infection in cancer patients receiving granulocyte transfusions. PMID- 11783436 TI - Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. PMID- 11783437 TI - Blood levels of vascular endothelial growth factor in obstructive sleep apnea hypopnea syndrome. PMID- 11783438 TI - Oxygen saturation in the bone marrow of healthy volunteers. PMID- 11783439 TI - Localization of peripheral dopamine D1 and D2 receptors in rat and human seminal vesicles. AB - Dopamine, an established neurotransmitter in the central nervous system, is recognized for its role in penile erection and ejaculation in rats. However, its complete mechanism of action in the genitourinary tract is unknown. The objective of this study was to investigate the existence and expression of peripheral dopamine D1 and D2 receptor messenger RNAs (mRNAs) and corresponding proteins in rat and human seminal vesicles. The seminal vesicle tissues of male Sprague Dawley rats and human radical prostatectomy specimens were used to extract total RNA and proteins, and to prepare slide sections. Rat hypothalamus tissue served as a control for dopamine D1 and D2 receptors. Testing for the presence and expression of peripheral dopamine D1 and D2 receptor mRNAs in rat and human seminal vesicle tissues was performed by reverse transcription-polymerase chain reaction. Western blotting was used to detect corresponding proteins of D1 and D2 receptors. Immunohistochemical staining using rabbit antipeptide polyclonal antibodies was employed to identify and anatomically localize dopamine D1 and D2 receptor proteins in rat and human seminal vesicles. Dopamine D1 and D2 receptor transcripts were detected in both human and rat seminal vesicle tissues. Western blot analysis demonstrated that peripheral dopamine D1 and D2 receptor proteins exist in both human and rat seminal vesicle tissues. Immunohistochemical analysis demonstrated the localization of peripheral dopamine D1 and D2 receptors to the smooth muscle layer of human and rat seminal vesicles. The results of this study demonstrate that peripheral dopamine D1 and D2 receptors are present in the seminal vesicle tissue in both rats and humans. Although these results suggest that seminal emission may be mediated in part by the stimulation of peripheral dopamine receptors located in the seminal vesicles, the functional significance of dopamine in male reproductive tract has yet to be fully defined. PMID- 11783440 TI - Peptidergic innervation of blood vessels and interstitial cells in the testis of the cat. AB - We studied the innervation of the cat testis using a panel of antisera against the following neuronal markers: protein gene product 9.5 (PGP), neuropeptide Y, C terminal peptide of neuropeptide Y, galanin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide, and substance P. Immunoreactivity against PGP, a general neuronal label, demonstrated the arrangement of fibers from the superior spermatic nerve (SSN) in the testicular pedicle and the cephalic testicular pole, and those of the inferior spermatic nerve (ISN) along the vas deferens and the inferior testicular ligament. The testicular parenchyma exhibited a very rich innervation, mainly distributed to blood vessels and Leydig cell nests, but also in close association with seminiferous tubules. Numerous peptidergic fibers were present in the SSN and ISN, albeit in different proportions. Thus, VIP immunoreactive fibers were almost absent in the SSN, but were the most abundant subpopulation of the ISN. The testicular interstitium contained numerous peptidergic fibers, associated with blood vessels, interstitial Leydig cells, and seminiferous tubules. Similar fibers were related to the rete testis. Parenchymatous VIP-immunoreactive nerves disappeared after bilateral vasectomy. Stimulation of the ISN under experimental conditions was associated with an increase of blood flow, and induced a large release of VIP into the spermatic vein. The extensive and selective distribution of nerve fibers within the cat testicular parenchyma supports the importance of spermatic nerves for testicular function. Furthermore, the differences in the fiber composition of the SSN and ISN can be correlated with their opposing effects on testosterone secretion and testicular blood flow. PMID- 11783441 TI - Motor imagery during hypnotic arm paralysis in high and low hypnotizable subjects. AB - Previous research suggests that conversion disordered patients with hand/arm paralysis exhibit slowed reaction times for mental hand-rotation tasks that correspond to their affected arm when the tasks are explicitly instructed and not when they are implicitly cued. Because of the many similarities between hypnotic phenomena and conversion symptoms, the authors tested whether similar motor imagery impairment would occur among normal high hypnotizable subjects when paralysis is suggested. Nine high and 8 low hypnotizable subjects were administered an implicit and an explicit mental hand-rotation task during hypnotically suggested paralysis of the right arm. On the implicit task, there were no significant reaction time (RT) differences between highs and lows. On the explicit task, only highs showed a significantly larger RT increase per degree of rotation with the paralyzed arm, compared to the normal arm. These preliminary findings suggest that the motor imagery impairment observed in conversion paralysis can be induced in highs using hypnosis. PMID- 11783442 TI - Angular range for reflection of p-polarized light at the surface of an absorbing medium with reflectance below that at normal incidence. AB - The range of incidence angle, 0 < phi < phi(e), over which p-polarized light is reflected at interfaces between transparent and absorbing media with reflectance below that at normal incidence is determined. Contours of constant phi(e) in the complex plane of the relative dielectric constant epsilon are presented. A method for determining the real and imaginary parts of the complex refractive index, epsilon(1/2) = n + jk, which is based on measuring phi(e) and the pseudo-Brewster angle phi(pB), is viable in the domain of fractional optical constants, n, k < 1. PMID- 11783443 TI - Canadian Society of Otolaryngology--Head and Neck Surgery 2000-2001 membership guide. PMID- 11783444 TI - Abstracts of the 10th Annual Meeting of the Israel Society of Neurosciences. Eilat, Israel, December 16-18, 2001. PMID- 11783454 TI - Brain-Gut Axis in Gastrointestinal Protection and Damage. 15 September 2001, Cracow, Poland. Abstracts. PMID- 11783455 TI - Nisin resistance distinguishes Mycoplasma spp. from Acholeplasma spp. and provides a basis for selective growth media. AB - The sensitivity of 11 Mycoplasma and 5 Acholeplasma species to the bacteriocin nisin was determined. When applied on filter paper discs to lawns of acholeplasma cells, nisin (20 nmol per disc) gave 3.5- to 7.0-mm zones of growth inhibition. The inclusion of 0.2 mM nisin in agar medium reduced the number of Acholeplasma laidlawii colonies by a factor of more than 10(6), and in a salts solution, 75 microM nisin killed more than 99.9% of cells within 1 min. Under similar conditions, nisin had no significant effect upon the growth or survival of Mycoplasma species. At low concentrations (1 to 3 microM), nisin stimulated glucose oxidation by A. laidlawii and Acholeplasma oculi. However, in comparison with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a recognized protonophore and uncoupler of respiration, the maximum extent of stimulation was low, < or = 20%, compared with up to 180% for CCCP. Also, in contrast to results obtained with CCCP, at concentrations only slightly above those causing stimulation of acholeplasma oxygen uptake, nisin strongly inhibited respiration. Inhibition of oxygen uptake was greater for A. laidlawii cells grown in the absence of cholesterol, and on agar medium, growth inhibition by nisin decreased with increasing concentrations of cholesterol. Nisin resistance may be a valuable characteristic in the selection and identification of Mycoplasma spp. PMID- 11783456 TI - Nedocromil sodium in golfers with seasonal allergic conjunctivitis. AB - To evaluate nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis, 24 golfers with documented ragweed-pollen allergy instilled eyedrops twice daily for 4 days prior to golf-course intervention and 15 minutes before playing a round of golf during peak ragweed season. Ocular symptoms were scored at baseline (7 days before golfing), prior to instillation on the day of golf, and 30 minutes, and 1, 4, 8, and 12 hours after tee-off. Physician assessment was performed prior to tee-off, before tee-off on the ninth hole, and at the end of the 18th hole. Itching, burning, grittiness, tearing, redness, and light sensitivity were significantly decreased after nedocromil administration, as were erythema, edema, conjunctival hyperemia, and overall findings in the conjunctiva. Symptom severity scores fell approximately 30 minutes after instillation, with improvements persisting 8 and 12 hours after treatment. Most patients (92%) rated the treatment moderately or completely effective, and 83% were willing to continue its use. Physician assessments of effectiveness agreed with those of the patients. In this open-label study, nedocromil sodium eyedrops relieved the ocular symptoms of seasonal allergic conjunctivitis for up to 12 hours, well beyond a usual round of golf. PMID- 11783457 TI - Effects of common ophthalmic preservatives on ocular health. AB - Preservatives are an important component of ophthalmic preparations, providing antimicrobial activity in the bottle and preventing decomposition of active drug. Often underrecognized, however, are the significant cytotoxic effects of preservatives associated with long-term therapy and especially use of multiple preserved drugs. The most common preservatives in ophthalmic preparations for glaucoma and surface eye disease-benzalkonium chloride (BAK), chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC)-were reviewed. Compared with other preservatives, SOC caused the least amount of damage to rabbit corneal epithelial cells. BAK has demonstrated cytotoxic effects in cell culture, as well as in animal and human studies. Physicians should consider treatment with new generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications. PMID- 11783459 TI - Addition of conjugated linoleic acid to a herbal anticellulite pill. AB - This study investigated the effect of a herbal anticellulite pill on visible cellulite in the thighs. Sixty female volunteers took a herbal anticellulite pill or a herbal anticellulite pill plus supplements of conjugated linoleic acid for 60 days. The combination treatment had a beneficial effect in as many as 75% of the women. The appearance of the skin improved significantly, and thigh circumference was reduced by an average of 0.88 inch. Further investigation in a larger, longer placebo-controlled trial is warranted. PMID- 11783458 TI - Over-the-counter oral nonsteroidal anti-inflammatory drugs: a pharmacoepidemiologic study in southern Italy. AB - The Pharmacoepidemiologic Service of the Second University of Naples analyzed the use and tolerability of over-the-counter (OTC) oral nonsteroidal anti inflammatory drugs (NSAIDs) purchased in Campania, a region of southern Italy. Forty private pharmacies uniformly distributed throughout the region were recruited. The study was conducted by means of a questionnaire completed by purchasers and lasted from December 1, 1999 to March 31, 2000; 2,053 questionnaires were collected. The age of respondents averaged 45.3 +/- 3.49 years (range, 17-85 years). The NSAIDs analyzed were acetylsalicylic acid, paracetamol, ibuprofen, ketoprofen, diclofenac, and piroxicam. Adverse effects, mainly gastrointestinal symptoms, were reported by 5.5% of the users and occurred primarily with diclofenac, piroxicam, ibuprofen, and ketoprofen. Because the use and availability of OTC NSAIDs are increasing, further studies of the tolerability of this important drug class are warranted. PMID- 11783460 TI - Carob pulp preparation for treatment of hypercholesterolemia. AB - The lipid-lowering effect of a carob pulp preparation rich in insoluble dietary fiber and polyphenols was investigated in a noncomparative, open-label pilot study. Over 8 weeks, 47 volunteers with moderate hypercholesterolemia (total cholesterol 232-302 mg/dL) consumed 15 g of carob per day in three products (breakfast cereal, fruit muesli bar, powdered drink) as a supplement to their regular diet. After 4 weeks, reductions of 7.1% in mean total cholesterol and 10.6% in LDL cholesterol were noted; respective decreases after 6 weeks were 7.8% and 12.2% (all P<.001). HDL cholesterol and triglyceride levels remained unchanged. Overall compliance was good. Only 3 volunteers (6%) reported a sensation of fullness, which led to 2 of the 3 dropouts. The carob preparation may have value in the dietary treatment of hypercholesterolemia. PMID- 11783461 TI - Purine and pyrimidine metabolism between millennia: what has been accomplished, what has to be done? PMID- 11783462 TI - Purine nucleotide catabolism in rat liver. PMID- 11783463 TI - Further refinement on the engineering of adenosine phosphorylase from purine nucleoside phosphorylase. PMID- 11783464 TI - Mutations in the hypoxanthine-guanine phosphoribosyltransferase gene in Spanish HPRT deficient families. PMID- 11783465 TI - Human guanine deaminase: cloning, expression and characterisation. PMID- 11783466 TI - The human NUDT family of nucleotide hydrolases. Enzymes of diverse substrate specificity. PMID- 11783467 TI - Inhibitors of NTPDase: key players in the metabolism of extracellular purines. PMID- 11783468 TI - Apoptosis-inducing cleavage of caspases by trimidox, an inhibitor of ribonucleotide reductase. PMID- 11783469 TI - Increased visceral fat accumulation in patients with primary gout. PMID- 11783470 TI - Serum uric acid levels and microalbuminuria in mild hypertensive patients. PMID- 11783471 TI - Guanosine-5'-triphosphate increases in red blood cells of heart transplant recipients treated with mycophenolate mofetil. PMID- 11783472 TI - Adenine incorporation in endothelial cells. PMID- 11783473 TI - TNF-alpha reduces the activity of ecto-5'-nucleotidase in human endothelial cells. PMID- 11783474 TI - The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. PMID- 11783475 TI - Influence of age and heat stress on cardiac function and nucleotide levels. PMID- 11783476 TI - The role of 5'-deoxy-5'-methyl thioadenosine phosphorylase in cardiac adenosine breakdown and adenine production. PMID- 11783477 TI - The effect of adenosine metabolism inhibition and nucleotide precursor supply on adenosine production in human heart endothelial cells. PMID- 11783478 TI - Enhanced endogenous adenosine production and protection of the heart after transplantation. PMID- 11783479 TI - Role of bovine hemoglobin enriched cardioplegia in myocardial preservation. PMID- 11783481 TI - Genomic structure of galectin-9 gene. Mutation analysis of a putative human urate channel/transporter. PMID- 11783480 TI - Identification of the potential sensitive urate/PAH transporter from LLC-PK1 kidney epithelial, cells. PMID- 11783482 TI - Effect of losartan and furosemide on the urinary excretion of oxypurinol and uric acid. PMID- 11783483 TI - P2y and P2x purinoceptors are respectively implicated in endothelium- dependent relaxation and endothelium independent contraction in human corpus cavernosum. PMID- 11783484 TI - ATP-triggered calcium signals in human neutrophils. PMID- 11783485 TI - The role of A1/A3 adenosine receptor activation in reduction of cardiomyocyte injury caused by hypoxic stress and in induction of apoptosis in rat cardiomyocyte cultures. PMID- 11783486 TI - Blockade of A1 receptors by caffeine induces c-fos, zif-268 and ARC expression in the striatum through different interactions with the dopamine system. PMID- 11783487 TI - Role of K(ATP) channels in the induction of ischemic tolerance by the 'adenosine mechanism' in neuronal cultures. PMID- 11783488 TI - Adenosine-induced caspase activity in N1E-115 cells. PMID- 11783489 TI - Effect of adenosine receptor agonists and antagonists on transport of adenosine in bovine heart microvascular endothelial cells. PMID- 11783490 TI - Deletion in the hypoxanthine phosphoribosyltransferase gene caused by Alu-Alu recombination in two Japanese patients with Lesch-Nyhan syndrome. PMID- 11783491 TI - Defects of pyrimidine degradation: clinical, molecular and diagnostic aspects. PMID- 11783493 TI - Dihydropyrimidine dehydrogenase (DPD) deficiency: novel mutations in the DPD gene. PMID- 11783492 TI - Confirmation of the enzyme defect in the first case of beta-ureidopropionase deficiency. Beta-alanine deficiency. PMID- 11783494 TI - Dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil associated toxicity. PMID- 11783495 TI - Isoforms of human CTP synthetase. PMID- 11783496 TI - Polyclonal antibodies against the ultrafast multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster. PMID- 11783497 TI - Inhibition and localization of human and rat dihydroorotate dehydrogenase. PMID- 11783498 TI - 6-mercaptopurine: efficacy and bone marrow toxicity in childhood acute lymphoblastic leukemia. Association with low (thio)purine enzyme activity. PMID- 11783499 TI - Recovery of SK-N-BE(2)c cells from treatment with cyclopentenyl cytosine. PMID- 11783500 TI - Effect of phosphorylation on deoxycytidine kinase activity. PMID- 11783501 TI - The role of deoxycytidine kinase in gemcitabine cytotoxicity. PMID- 11783502 TI - Novel genetic mutations responsible for the HPRT deficiency and the clinical phenotypes in Japanese. PMID- 11783503 TI - Thymidine phosphorylase in angiogenesis and drug resistance. Homology with platelet-derived endothelial cell growth factor. PMID- 11783504 TI - Secretion of thymidine by hybridoma cells. PMID- 11783506 TI - 2-chlorodeoxyadenosine (2-CdA) does not change the expression of Fas antigen on chronic lymphocytic leukaemia cells. PMID- 11783505 TI - Thymidylate synthase inhibition induces p53 dependent and independent cell death. PMID- 11783507 TI - Cyclopentenyl cytosine increases the phosphorylation and incorporation into dna of arabinofu-ranosyl cytosine in a myeloid leukemic cell-line. PMID- 11783508 TI - Cyclopentenyl cytosine induces apoptosis and secondary necrosis in a T lymphoblastic leukemic cell-line. PMID- 11783509 TI - Thiopurine methyl transferase: activity and genotyping in patients with acute lymphoblastic leukemia. PMID- 11783510 TI - Hyperthermy increase the phosphorylation of deoxycytidine in the membrane phospholipid precursors and decrease its incorporation into DNA. PMID- 11783511 TI - Purine nucleotide metabolism in chronic lymphocytic leukemia lymphocytes. PMID- 11783512 TI - Inhibition of dna methylation by 5-aza-2'-deoxycytidine correlates with induction of K562 cells differentiation. PMID- 11783513 TI - Evidence of inhibition of DNA methylation by fludarabine. PMID- 11783514 TI - Adenoviruses encoding HPRT correct the biochemical abnormalities fully only in HPRT-deficient human cell lines: importance of species differences. PMID- 11783515 TI - The cytotoxic effect of purine riboside on COS-7 cells. PMID- 11783516 TI - Methylated and non methylated thiopurine nucleotide ratio (Me6-MPN/6-TGN): usefulness in the monitoring of azathioprine therapy? PMID- 11783517 TI - Organ preservation during experimental liver transplantation. PMID- 11783518 TI - Extraction and purification of ecto-5'-nucleotidase from human lymphocytes. PMID- 11783519 TI - HPLC/ESI tandem-MS of liquid urine or urine soaked filter-paper strips for the detection of thymine-uraciluria and dihydropyrimidinuria. PMID- 11783520 TI - Screening for purine and pyrimidine disorders using dried urine spots. PMID- 11783521 TI - Determination of methylated purine bases in urine from healthy subjects. PMID- 11783522 TI - Decrease in urinary uric acid concentrations after urine storage. PMID- 11783523 TI - Mass spectrometry for analysis of purine and pyrimidine compounds. PMID- 11783524 TI - Biochemical and immunological abnormalities in purine nucleoside phosphorylase deficient mice. PMID- 11783526 TI - Cell type-specific differential expression of human PRPP synthetase (PRPS) genes. PMID- 11783525 TI - Carrier erythrocyte entrapped adenosine deaminase therapy in adenosine deaminase deficiency. PMID- 11783527 TI - ADA activity and DATP levels in erythrocytes after bone marrow transplantation. PMID- 11783528 TI - Adenosine deaminase-deficient mice: models for the study of lymphocyte development and adenosine signaling. PMID- 11783529 TI - Inhibition of fetal thymic caspases abrogates the consequences of adenosine deaminase deficiency. PMID- 11783530 TI - Erythrocyte amp deaminase deficiency in Japanese: a compound heterozygote responsible for the complete deficiency. PMID- 11783531 TI - Effect of uridine administration to a patient with adenylosuccinate lyase deficiency. PMID- 11783532 TI - Adenylosuccinate lyase deficiency: from the clinics to molecular biology. PMID- 11783533 TI - Polymorphic markers in the XDH gene as diagnostic tools for typing classical xanthinuria. PMID- 11783534 TI - NAPDD patients exhibit altered electrophoretic mobility of cytosolic 5' nucleotidase. PMID- 11783535 TI - Purines, lactate and myo-inositol in CSF might reflect excitotoxicity in inherited metabolic disorders. PMID- 11783536 TI - Cerebrospinal fluid purines, pyrimidines, organic acids and amino acids in neonatal citrullinaemia. PMID- 11783537 TI - Old age from an existential-analytical perspective. AB - Aging confronts humans with specific existential issues. They frequently cause suffering in old age. Not dealing with or insufficiently dealing with these existential themes may result in crisis, psychological disorders, and illness. By integrating existential themes of aging into the understanding of one's own life, the process of aging contributes to personal maturity. PMID- 11783538 TI - Attitudes towards handicaps in South African and Indian university students. AB - 327 first-year students in South Africa showed a significantly more favourable attitude towards handicaps than 205 first-year Indian students. PMID- 11783539 TI - A developmental model of vulnerability to suicide: consistency with some recurrent findings. AB - Converging evidence from family, twin, adoption, brain biochemistry, and nuclear biological studies suggests that vulnerability to suicide may be genetically determined. Secondly, there is evidence that the predisposition to suicide remains latent until it becomes activated during puberty. Thirdly, for a suicide attempt to occur, the activated predisposition must be triggered by a stressor. This three-stage developmental model is shown to be consistent with some major demographic, epidemiological, and other correlates of suicide. PMID- 11783540 TI - Attitudes toward animal research among psychology students in Spain. AB - Animal research plays a central role in psychology, and its use, prevalence and quality depends on the attitudes of students who enter psychology in Spain. Attitudes among psychology students about the use of laboratory animals are not known, so the aim of this work was to analyze the attitudes of Spanish psychology students toward animal research. An attitude questionnaire of 15 items was given to 661 undergraduate students of the School of Psychology at the University of Malaga, Spain. Several results were found: (a) 65.7% of the respondents strongly agreed or agreed with animal research. General support for animal research was significantly higher by men than by women. (b) Support for animal research was higher for senior students, suggesting that the psychology curriculum or self selection to remain in the program might influence students' attitudes. (c) Attitudes toward animal research were similar among students independent of the type of animal being used for research in biological or psychological studies. (d) 58% considered that laboratory animals never or almost never are inappropriately handled. (c) 55.6% indicated that research in psychology on animals could be generalized to humans. Overall, these results suggest that among Spanish psychology students animals research is considered important for the advancement of the science. Likewise, a majority of students displayed positive attitudes toward animal research. PMID- 11783541 TI - Conjunctive measurement of aquatic exercise in an office setting. AB - The Hydrotrack, a treadmill immersed in a water bath, is designed to provide an in-office approach to aquatic therapy. 24 clinical clients in an outpatient sports medicine practice were invited to use the Hydrotrack as part of their rehabilitation treatment. Our purpose was to describe the way(s) in which the Hydrotrack is useful in rehabilitation treatment. Exercise protocols designed by a physical therapist were used for each subject. We monitored an external criterion, heart rate, to measure the subjects' exertion during the exercise process. Self-reported ratings of exercise efficacy and exertion were also used to quantify the subjects' performance on the Hydrotrack. Heart-rate values and self-report ratings supported the usefulness of this device in physical therapy. PMID- 11783542 TI - Comparison of French and Japanese individuals with reference to Hofstede's concepts of Individualism and Masculinity. AB - The purpose was to examine whether Japanese individuals were oriented toward collective and masculine values attributed to cultures by Hofstede by comparing them with those of French individuals. There were 110 French participants (54 men, 56 women) and 128 Japanese participants (41 men, 87 women), selected from undergraduate students, employed workers, housewives, and retirees. Their occupational proportion and their ranges of age were balanced in both countries. Scales for Individualism and Masculinity dealt not only with work-related but also general items for workplace, culture, education, and family. Analyses generally showed that the Japanese individuals scored higher on the Masculinity scale and French participants scored higher on the Individualism scale. There was a mean difference between Japanese men and women in how they answered questions about the work-related items concerning Masculinity. PMID- 11783543 TI - Women report being more likely than men to model their relationships after what they have seen on TV. AB - Students (21 men and 50 women) anonymously answered questions about imitating relationships seen on TV. The women were more likely than men to report trying to model family life after what they saw on TV situational comedies and to expect their significant other to act as those seen on TV. They also more frequently reported experiencing a significant other acting as those on TV. There was no difference by sex in current age, parents' marital status during the students' formative years, or age of separation, divorce, or widowing if any occurred. For neither women nor men did a broken home during the formative years correlate with looking to TV for information on relationships. PMID- 11783544 TI - Relationship between male infants' vocal responses to mother and stranger at three months and self-reported academic attainment and adjustment measures in adulthood. AB - This study explored whether 3-mo.-old male infants' differential vocal response to mother vs a female stranger, which has been related to cognitive and academic functioning up to 12 years of age, is also related to adult development. Of the 12 subjects who had been seen from infancy through 12 years, 10 were located at Ages 21 and 28 years and were asked about their high school grade point average, scores on the SAT, years of schooling, emotional adjustment, substance abuse, and if they were in a stable relationship by the age 28. Responses showed 3-mo.-olds' differential vocal response was related positively to high school grade point average, scores on the SAT, years of completed education by age 28, and stability of relationship by age 28, and negatively related to substance abuse. No relationship was found between differential vocal response and reported emotional problems. Results suggest that early infant social interactions may be linked to adult development or adjustment. PMID- 11783545 TI - Beyond the gambling paradigm: internal controllability in decision-making. AB - Much research within decision-making has used the standard gambling paradigm, where decision outcomes depend only on chance. Many real life decisions, however, imply personal control over decision outcomes. This paper addressed the question of how internal controllability influences decision-making. Internal controllability is assumed (i) to enhance unrealistic optimism and (ii) to result in a better cost:benefit ratio. Both tendencies support each other and predict an enhanced attractiveness for internal and controllable choice options. Participants read a scenario and made a decision afterwards. Results supported the prediction: decision-makers take the option they can personally control. This finding widens the narrow perspective inherent in much previous research based on the gambling paradigm. PMID- 11783546 TI - A robust method for the analysis of experiments with ordered treatment levels. AB - A robust approach for the analysis of experiments with ordered treatment levels is presented as an alternative to existing approaches such as the parametric Abelson-Tukey test for monotone alternatives and the nonparametric Terpstra Jonckheere test. The method integrates the familiar Spearman rank-order correlation with bootstrap routines to provide magnitude of association measures, p values, and confidence intervals for magnitude of association measures. The advantages of this method relative to five alternative approaches are pointed out. PMID- 11783547 TI - Screening for major depressive disorders in adolescent psychiatric inpatients with the mood modules from the Primary Care Evaluation of Mental Disorders and the Patient Health Questionnaire. AB - The mood modules from the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Patient Health Questionnaire (PHQ) were administered to 17 (52%) female and 16 (48%) male adolescent (13-17 years old) psychiatric inpatients. The internal consistencies of both were good (KR-20 for PRIME-MD=.80, Cronbach coefficient alpha for Patient Health Questionnaire=.85). The correlation between the PRIME-MD and Patient Health Questionnaire total scores was .87 (p<.001), and the point-biserial correlation of both questionnaires' total scores with being diagnosed with a Major Depressive Disorder was .54 (p<.001). Both mood modules appeared to be equally effective in screening for a Major Depressive Disorder. PMID- 11783548 TI - Development of reading proficiency in English by bilingual children and their monolingual peers. AB - The semantic, syntactic, and graphophonic cueing techniques employed by 55 bilingual children and 39 monolingual peers when reading aloud in English were identified through miscue analysis. In contrast to earlier research in 1999 by Cline and Cozens no significant differences were found between the two groups on any of the techniques. Both bilingual and monolingual readers consistently used more graphophonic cues than syntactic or semantic cues but not significantly so. The authors discuss possible extraneous variables which may account in part for this unexpected result. PMID- 11783549 TI - Predicting suicidal ideation in high school students. AB - In a sample of 77 high school students, current suicidal ideation was predicted by depression, music preferences, and reasons for living scores. PMID- 11783550 TI - Loneliness and self-efficacy in education majors. AB - The aim of the study was to investigate the relationship between loneliness and self-efficacy for a sample of 314 French Canadian education majors who were administered French Canadian versions of the UCLA Loneliness Scale and Teacher Efficacy Scale. Analysis yielded, as expected, a negative and significant correlation of -.25 between scores on loneliness and self-efficacy. PMID- 11783551 TI - Attitudes toward abortion. AB - In a sample of 60 undergraduates, opposition to abortion was associated with trust and reliance in God rather than the government or oneself. PMID- 11783552 TI - On the far reaching effects of using biased estimates of score reliability: an examination of the problem in 20 data analyses. AB - Violation of either of two basic assumptions in classical test theory may lead to biased estimates of reliability. Violation of the assumption of essential tau equivalence may produce underestimates, and the presence of correlated errors among measurement units may result in overestimates. The ubiquity of circumstances in which this problem may occur is not fully comprehended by many workers. This article surveys a variety of settings in which biased reliability estimates may be found in an effort to increase awareness of the prevalence of the problem. PMID- 11783553 TI - Biographical factors of occupational independence. AB - The present study examined biographical factors of occupational independence including any kind of nonemployed profession. Participants were 59 occupationally independent and 58 employed persons of different age (M = 36.3 yr.), sex, and profession. They were interviewed on variables like family influence, educational background, occupational role models, and critical events for choosing a particular type of occupational career. The obtained results show that occupationally independent people reported stronger family ties, experienced fewer restrictions of formal education, and remembered fewer negative role models than the employed people. Implications of these results are discussed. PMID- 11783554 TI - Blocking the box: an informal look. AB - Data for 32 1-hr. observations in a residential community showed about 200 violations of a traffic regulation requiring motorists to keep intersections clear. Women driving vans were the least compliant--accounting for approximately 40% of the total. PMID- 11783555 TI - Raising the graduation bar for the schools: expectations vs outcomes. AB - Educational reform is an ongoing concern of parents, educators, policy makers, and the public at large. The past 50 years have ushered in a new era of reform, whose major objective was to improve students' performance based on the use of statewide standardized testing and changes in graduation requirements. This study examined one such reform movement, initially developed during the late 1970s, which developed minimum competency testing standards as well as increased course demands to specify graduation requirements for public high school students. The outcomes for this reform model, both in terms of students' achievement and failure, did not meet expectations. PMID- 11783556 TI - Tuberculosis and suicide. AB - Formerly eastern European nations had higher rates of mortality from suicide and tuberculosis in 1990 and 1995 and a greater increase in these rates over the 5 yr. period than western European nations. PMID- 11783557 TI - Does supervision by a lifeguard make a difference in rule violations? Effects of lifeguards' scanning. AB - Systematic observations were made of five lifeguards at indoor public swimming pools. Scanning by lifeguards was associated with lower incidences of rule violations by swimmers. Greater numbers of lifeguards patrolling the pool areas tended to reduce violations. Rules violations tended to be fewer when adult-to child ratios were low, suggesting that monitoring by a parent or an adult may encourage rule compliance. PMID- 11783558 TI - Vicarious stress: patterns of disturbance and use of mental health services by those indirectly affected by the Oklahoma City bombing. AB - This study explored the intermediate psychological effects of terrorism on adults not directly affected by the Oklahoma City bombing by examining the course of PTSD and subthreshold PTSD symptoms over time and whether treatment affected this course. The respondents were interviewed at 3-mo. intervals for 18 mo. following an initial 6-mo. survey. Analysis suggested avoidance, re-experiencing, and increased arousal symptoms in this population were limited over time, declining with or without treatment between 6 and 9 mo. Conversely, victimization symptoms remained high without mental health intervention for the first year after the disaster. The study also examined the nature and occurrence of comorbidity in groups seeking and not seeking treatment. PMID- 11783559 TI - Prevalence of cigarette smoking in Iran. AB - The current research assessed the prevalence of cigarette smoking in Shiraz, Iran by randomly selecting 1,335 subjects (782 men and 553 women) from the city for a face-to-face interview and completion of a questionnaire. Of the participants, 205 (26%) of the men and 20 (3.6%) of the women reported being current smokers. The mean ages of smokers and nonsmokers were 41.8 and 37.0 yr., respectively (range between 16 and 90 years for smokers and nonsmokers). The mean age of starting to smoke cigarettes was 21.3 yr. (range of 10 to 60). The most common reasons for current cigarette smoking were Need to avoid withdrawal symptoms, Release of tension, and Pleasurable purposes. Foreign filter-tipped cigarettes were the most common type consumed. The mean number of cigarettes per day was 13.4 (SD = 10.3). Reports for onset of cigarette smoking included Modeling, Release of tension, and Pleasurable purposes. Cigarette smoking was reported by more males than females. The most common reason for onset of cigarette smoking was different from that for current smoking. Frequencies of smokers within age groups were varied. PMID- 11783560 TI - Aversive and attractive properties of electrical stimulation for Paramecium caudatum. AB - Although there are data to show that mild electrical stimulation from a cathode source can serve as positive or attractive stimulus for paramecia, the properties of anode stimulation have not been clear. This research gives evidence to support the previously reported positive properties of cathode stimulation but showed that anode stimulation has opposite (negative or aversive) properties. PMID- 11783561 TI - A longitudinal study of active treatment of adaptive skills of individuals with profound mental retardation. AB - A longitudinal study indicated that a single group of adults living in a large state institution (O'Berry Center in Goldsboro, North Carolina) benefited from receiving active treatment, although no control group was permitted. After five years, 59 individuals with profound mental retardation improved their skills in six general areas of dressing, grooming, eating, toileting, communication, and social interaction. After five more years of active treatment, 51 persons who had remained in the program maintained their skills in dressing, grooming, eating, and communication. Significant improvement in the use of toilet and a loss in social interaction were observed. Although the participants were 10 years older at the end of this study, their adaptive behaviors, in comparison to the date of entry, either improved or were maintained. Therefore, aging was not associated with decline in skills. PMID- 11783562 TI - Prevalence of childhood and adolescent sexual abuse among sex offenders. AB - A simple nonstandardized questionnaire was developed and administered to 150 men convicted of various sexual offenses currently on probation or parole, living in the community, admitting their offenses and attending treatment. The hypothesis that men who engaged in sexual activity as adolescents with women would be at a higher risk of committing statutory rape-type sexual offenses was not substantiated. PMID- 11783563 TI - Substance use among Iranian psychiatric inpatients. AB - This study evaluated substance use among a sample of 205 psychiatric inpatients (70 women and 135 men) chosen randomly. The subjects (who had schizophrenia or mood disorders) were evaluated on a confidential questionnaire by interview. Their mean age was 35 yr. (SD= 10.4, range 16 to 69). Of these participants, 76% of the 135 men and 34% of the 70 women admitted use of substances: cigarettes (74% of men, 31.4% of women), opiates (31.9% of men, 4.3% of women), alcohol (23.7% of men, 4.3% of women), hashish (8.9% of men, no women), marijuana (3.7% of men, no women), and cocaine or LSD by none. Only 27% of the women and 63% of the men reported still using substances regularly; some reported using more than one substance. Of the current users, 61.8% of the schizophrenics, 20% of unipolar depressed, and 37.5% of bipolar patients reported current use. The reasons for substance use in order of frequencies of mention were release of tension, seeking pleasure, and need (to avoid withdrawal symptoms) by men and habit, seeking pleasure, and need by women. PMID- 11783564 TI - Relationship between television viewing frequency and scores on shyness among Philippine high school students. AB - The association between frequency of watching TV and scores on a measure of shyness was estimated for a sample of 3,307 Philippine high school students (1,267 boys and 1,819 girls). Students who watched more than 5 hours of TV a day scored significantly higher on shyness than students who watch less TV. PMID- 11783565 TI - Diversity and the handicapped: an informal look. AB - Data for viewings of 58 television game shows suggests none of the 157 observed contestants to be physically handicapped. PMID- 11783566 TI - Prediction of three social cognitive-motivational structure types. AB - Previously, using interviews from Baumrind's longitudinal study, three cognitive motivational structures (CMSs) were predicted in 68 adolescents from caregiving settings and from the CMS types of their mothers, based on the mothers' interviews elicited six years earlier. CMS theory proposes that during Piaget's Concrete Operational Period care-receiving influences the child's adoption of a social cognitive style, which corresponds to one of Piaget's stages of cognitive development. One who is classified as an Operational experiences the caregiving setting as tuned to the child's long-term interests, becomes focused on function and control of function and grasps the distinctions between and gradations of social attributes. One classified as future Intuitive experiences the caregiving as insufficient or unreliable and becomes focused on getting and having, and assesses social situations based on current striking dimensions. A person classified as being future Symbolic experiences the caregiving as out of tune with the self or the world, becomes focused on identity and emotional closeness, and may define self or object by a single attribute. This previous study did not distinguish between the influence of caregiving (including mothers' CMS) on the formation of adolescent CMS type and the possible constancy of CMS type from ages 9 to 15 years. The current study was designed to distinguish between these two possibilities, using data from 67 of the same mothers. Mothers' interviews were purged of descriptions of her child's behavior. Another interview was composed of the purged descriptions of child behavior. This was also done for interviews held when the child was 4 and 15 as well as at 9. From interviews with descriptions of child behavior purged, mother's CMS type at the child's age of 4 and 9 yr. agreed with her adolescent's previously assigned CMS type (p<.05), and caregiving setting at 9 years predicted the adolescent's CMS type (p<.05). From interviews composed of descriptions of only the child's behavior, adolescent CMS type agreed with previously assigned adolescent CMS type (p<.01). Findings were consonant with the idea that CMS type formation is influenced at about Age 9 and sufficiently established to be recognized at Age 15. PMID- 11783567 TI - Construct validity for self-acceptance and fear of negative evaluation. AB - For 55 students (13 men, 42 women) there was a significant inverse correlation for scores on the Self-acceptance Scale and scores on the Fear of Negative Evaluation Scale, thereby giving credence to the construct validity of both scales, that is, the more one accepts oneself, the less negative evaluation there is of oneself. PMID- 11783568 TI - A scale for measuring students' anti-intellectualism. AB - Two studies were conducted which report the development and testing of the Student Anti-Intellectualism Scale, designed as a measure of anti-intellectual attitudes in students enrolled in higher education. The first study analyzed an initial 25-item scale to assess internal consistency and factorial structure. The second study examining a final version of the scale was conducted to test reliability and factorial structure, in addition to assessing evidence of construct validity. The second study also assessed temporal stability and social desirability response set. The studies indicated the scale had a fundamentally unidimensional structure and considerable internal consistency and also provided support for the validity of the anti-intellectualism constrict. Anti intellectualism is discussed in the context of personality theory, and suggestions are offered with reference to establishing anti-intellectualism as a trait relative to the five-factor model of personality. PMID- 11783569 TI - Controlling decremental and inflationary effects in reliability estimation resulting from violations of assumptions. AB - Two assumptions in classical test theory, essential tau-equivalence and independence of measurement errors, when violated may produce attenuated or inflated estimates of reliability, respectively. Inflation stemming from correlated errors can be controlled by a procedure in which systematically created equivalent halves of a given measuring instrument are administered across two occasions. When poor approximations to equivalent halves are constructed for this purpose, however, distortion in the opposite direction may result, being sometimes quite large when measuring instruments are not essentially tau equivalent (or, at the practical level, unidimensional). The nature of these decrements are discussed and illustrated, and a number of procedures for eliminating them introduced. PMID- 11783570 TI - Development of a questionnaire to measure concern for dental appearance. AB - 100 adults, selected for cosmetic dental treatment in a general dental practice, completed a 42-item questionnaire designed, on the basis of previous research and the author's clinical experience, to measure concern for dental appearance. This had high internal consistency and was reduced to a questionnaire of 23 items with internal consistency shown by a standardised Cronbach alpha of .84. An exploratory factor analysis with varimax rotation identified six factors, the main one appearing to be a measure of concern for dental appearance. The high internal consistency suggests that the total score for the revised questionnaire is a measure of a construct, concern for dental appearance. Although the simplest measure of that may be contained in the items for the first factor, a much larger sample would be necessary to confirm the complex factor structure and so the questionnaire's total score is probably the more reliable measure at present. A study is summarised showing that the total score provides a measure that, in statistical regression analysis, may predict the intentions of adults to take care of the appearance of their teeth. PMID- 11783571 TI - Prevalence of child psychological, physical, emotional, and ritualistic abuse among high school students in Mpumalanga Province, South Africa. AB - Based on self-reports the prevalence during childhood of psychological, physical, emotional, and ritualistic abuse among 559 high school students in Standards 7, 8, 9, and 10 of three high schools in the Mpumalanga Province of South Africa was examined. The questionnaire asked for the demographic information and experiences of psychological, physical, and emotional abuse by their parents or adult caretakers as well as ritualistic abusive experiences before they were 17 years of age plus an estimate of self-perceived abuse during childhood and an overall rating of their own childhood. Analysis showed the self-reported prevalence rates to be as follows: 70.7% psychologically abused (but 14.4% for extreme cases), 27.0% physically abused, 35.3% emotionally abused, and 10.0% ritualistically abused. 13.4% of those who reported themselves as psychologically abused, 20.7% of the physically abused, 19.3% of the emotionally abused, and 35.8% of the ritualistically abused perceive themselves as not abused in any form during childhood. Yet, of the psychologically abused 23.4%, of the physically abused 18.2%, of the emotionally abused 22.0%, and of the ritualistically abused 28.3% rated their childhood as 'very unhappy'. It appears these various forms of abuse are experienced by the participants as widespread, suggesting that a much more serious problem may exist than has been recognised. More research into those forms of child abuse in this Province and elsewhere is needed for a clear appreciation of the problems and the effects of such abuse in children's behavior. PMID- 11783572 TI - Violent versus nonviolent methods for suicide. AB - Violent and nonviolent suicide rates in the American states in 1980 showed different social correlates, but both patterns were different from those for homicide rates. PMID- 11783573 TI - Representation of the serial killer on the Italian Internet. AB - The representation of serial killers was examined from the analysis of 317 Web pages in the Italian language to study how the psychological profiles of serial killers are described on the Italian Internet. The correspondence analysis of the content of these Web pages shows that in Italy the serial killer is associated with words such as "monster" and "horror," which suggest and imply psychological perversion and aberrant acts. These traits are peculiar for the Italian scenario. PMID- 11783574 TI - The military participation rate and suicide rates in Italy, 1864-1913. AB - In Italy for the period 1864-1913, suicide rates were positively associated with the military participation rate. PMID- 11783575 TI - Discrepancy scores of reliabilities of the WAIS-III. AB - Internal consistency reliabilities for the WAIS-III IQ, Index, and subtest discrepancy scores are provided. The reliabilities range from .44 to .88. PMID- 11783576 TI - Measuring improvement or decline on the WAIS-R in inpatient psychiatry. AB - Psychologists in inpatient psychiatric settings sometimes are asked to assess whether patients improve or decline in intellectual functioning. The impetus for this referral question may be a perceived change in psychiatric status, an acute neuropathological event, e.g., a head injury, or a suspicion of an early dementing process. For this study, data from 100 inpatients who completed the WAIS-R on two separate admissions were used to calculate confidence bands for measurement error surrounding test-retest difference scores. The analysis indicated that, if the retest interval is three months or less, significant practice effects must be factored into the interpretation of difference scores. A table for the interpretation of difference scores at different testing intervals is provided PMID- 11783577 TI - A new sesquiterpene lactone glucoside from Ixeris sonchifolia. AB - A new sesquiterpene lactone glucoside, Ixerin Z1 (1), was isolated from the whole plants of Ixeris sonchifolia (Bge.) Hance, along with 15 known compounds. The structure of 1 was elucidated as 1(10),3,11(13)-guaiatriene-12,6-olide-2-one-3-O [6'-(p-hydroxyphenylacetyl)]-glucopyranoside by spectroscopic methods including 2D-NMR techniques. PMID- 11783578 TI - Structures of two new benzofuran derivatives from the bark of mulberry tree (Morus macroura Miq.). AB - Two new benzofuran derivatives, macrourins A (1) and B (2), together with two known stilbene derivatives, were isolated from the barks of Morus macroura Miq. Their structures were elucidated by means of spectroscopic evidence. PMID- 11783579 TI - A new naphthoquinone from Bombax malabaricum. AB - A new naphthoquinone 1 together with 7-hydroxycadalene (2) and 8-formyl-7-hydroxy 5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (3) were isolated from the heartwood of Bombax malabaricum. The new naphthoquinone was characterized as 7 hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (1) based on spectral and chemical studies. PMID- 11783580 TI - Annonaceous acetogenins of the seeds from Annona muricata. AB - Muricatenol (1) is a new C37 non-THF ring acetogenin with four hydroxyls and one isolated double bond in the long aliphatic chain. 2,4-cis-Gigantetrocinone (2) and 2,4-trans-gigantetrocinone (3) have been isolated as their acetates by preparative TLC. 2,4-trans-Isoannonacin-10-one (4) and 2,4-trans-isoannonacin (5) have been isolated as only 2,4-trans-form for the first time (no cis-form). Also four known acetogenins, gigantetrocin-A (6), gigantetrocin-B (7), annomontacin (8), gigantetronenin (9) and a mixture of N-fatty acyl tryptamines have been isolated (10). Their structures have been established on the basis of spectral analyses. The CHCl3 fraction of the seeds showed strong antitumor activities. PMID- 11783581 TI - Chemical constituents of Typhonium giganteum Engl. AB - A new cerebroside, named typhonoside (1), was isolated from the root tuber of Typhonium giganteum Engl. along with three known compounds dipalmitin (2), alpha monopalmitin (3) and 2,6-diamino-9-beta-D-ribofuranosylpurine (4). The structure of 1 was determined to be 1-O-beta-D-glucopyranosyl-(2S,3S,4R,8Z)-2-[(2'-hydroxyl docosanoyl)amino]-8-otadecene-1,3,4-triol on the basis of spectral data. PMID- 11783582 TI - A new sesquiterpene lactone from Tsoongiodendron odorum Chun. AB - A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5alpha, 6alpha, 7beta, 10beta- 11alpha, 13-dihydro-4(15) eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines. PMID- 11783583 TI - Quinquenoside L9 from leaves and stems of Panax quinquefolium L. AB - During additional chemical investigation on the saponin composition of leaves and stems of Panax quinquefolium L, a new minor dammarane saponin, quinquenoside L9 (1) has been obtained. By means of physico-chemical evidences and spectral analysis, its structure was elucidated 6-O-[alpha-L-rhamnopyranosyl-(1-2)-beta-D glucopyranosyl]-dammara-3beta, 6beta,12beta,20(S),24zeta,25-hexaol (1). PMID- 11783584 TI - Constituents from Limonia crenulata. AB - A new indole alkaloid, crenulatine (1), along with twenty known compounds, was isolated from the stems of Limonia Crenulata. Their structures were identified by spectral means. Those compounds include four alkaloids, four coumarins, two flavanones, three tetranortriterpenoids, one triterpenoid, three steroids, two lignans and two aromatic compounds. PMID- 11783585 TI - Chemical constituents from the leaves of Magnolia denudata. AB - 20 compounds were isolated from the leaves of Magnolia denudata including 16 lignans, which belong to 6 structural types. Except for (7R, 8S, 1'S)-delta8' 1', 4'- dihydro-5'-methoxy-3,4-methylenedioxy-4'-oxo-7.0.2', 8.1'-neolignan (6), magliflonenone (9), 2, 5'-diene-2', 8'-epoxy-5'-methoxy-8-methyl-4'-oxo-3,4- methylenedioxy-spiro (5, 5)-undecane (10), veraguensin (16) and beta-sitosterol (20), the other 15 compounds were obtained from this species for the first time. The absolute configurations of 3 compounds (1, 4, 10) were determined by CD spectroscopy for the first time. The anti-inflammatory activities of compounds 1, 2 and 16 were assessed and 2 was shown to have significant inhibition effect on mice hind-paw edema induced by carrageenan. PMID- 11783586 TI - A novel eleven-membered-ring triterpene dilactone, pseudolarolide F and A related compound, pseudolarolide E, from Pseudolarix kaempferi. AB - A novel eleven-membered-ring triterpene dilactone, pseudolarolide F (1), and a related compound, pseudolarolide E (2), were isolated from the seeds of Pseudolarix kaempferi, a plant indigenous to eastern China. Their structures and stereochemistry were established by spectroscopic studies, which included UV, IR, HREIMS, 2D NMR correlation methods (1H-1H COSY, 13C-H COSY, NOESY, HMQC, and HMBC), and single-crystal X-ray analysis. PMID- 11783587 TI - A new bicoumarin from Stellera chamaejasme L. AB - Thirteen compounds were isolated from roots of Stellera chamaejasme L. (Thymelaeaceae). They are 3-sitosterol (2), simplexin (3), pimelea factor P2 (4), daucosterol (5), (+)-3-hydroxy-1,5-diphenyl-1-pentanone (6), 4-ethoxy-benzoic acid (7), 2,4,6-Trimethoxy-benzoic acid (8), (+)-afzelechin (9), fumaric acid (10), N,N-dimethyl-L-aspartic acid (11), umbelliferone (12), daphniretin (13) and a novel bicoumarin named bicoumastechamin (1). Among the known compounds, 7, 8, 9, 10 and 11 were first isolated from this plant, and 6 was first isolated from the natural resources. Their structures have been elucidated on the basis of spectral data. In vitro bioassays showed that 4 inhibited cancer cell growth, 13 exhibited immunomodulatory activity, and 6 exhibited both immunomodulatory and anti-tumor activity. PMID- 11783588 TI - A new flavone glycoside, 5-hydroxy 7,3',4',5'-tetra-methoxyflavone 5-O-beta-D xylopyranosyl-(1-->2)-alpha-L-rhamnopyranoside from Bauhinia variegata Linn. AB - A new flavone glycoside m.f. C(30)H(36)O(15) m.p. 252-253 degrees C, [M]+ 636 (EIMS) was isolated from the acetone soluble fraction of the concentrated 95% ethanolic extract of the seeds of Bauhinia variegata (Linn). It was identified as 5-hydroxy7,3',4',5'-tetra-methoxyflavone 5-O-beta-D-xylopyranosyl-(1-->2)-alpha-L rhamnopyranoside (1) by various colour reactions, chemical degradations and spectral techniques. PMID- 11783589 TI - Triterpenoid saponin from Primula elatior subsp. meyeri. AB - A new triterpenoid saponin, protoprimuloside B (2), has been isolated from the roots of Primula elatior subsp. meyeri and its structure deduced as 3beta-O [[alpha-L-rhamnopyranosyl-(1-2)-beta-D-galactopyranosyl-(1-3)]-[beta-D glucopyranosyl-(1-2)]-beta-D-glucopyranosyl]-protoprimuloside B by means of spectral data, especially NMR (400 MHz), including 1H, 13C, DEPT, COSY, HMBC, HMQC, NOESY techniques and (+)FAB-MS spectrum. PMID- 11783590 TI - An in vitro study of the structure-activity relationships of sulfated polysaccharide from brown algae to its antioxidant effect. AB - In this paper, the structure-activity relationships of chemically modified uronic acid polymer fragments from brown algae with regard to their antioxidant effects on H2O2-damaged lymphocyte were studied. The results indicated that the most potent antioxidant activity was obtained from the sulfated polysaccharide with ratio of mannuronate blocks (M-blocks) to guluronate blocks (G-blocks) of 3 to 1 and carboxyl residue unesterified. The sulfated G-blocks with esterified carboxyl residue also prevented lymphocyte from injury. However, the sulfated G-blocks bearing unesterified carboxyl residue hardly exerted antioxidant activity. These findings suggested that both M-blocks and esterified carboxyl residue were determinant structures in preventing lymphocyte from being oxidized by H202, indicating that the existence of M-blocks was more important in scavenging free radicals. PMID- 11783591 TI - Pumps and lymphedema. PMID- 11783592 TI - Ultrasonography of arm edema after axillary dissection for breast cancer: a preliminary study. AB - This work examined whether ultrasonography (US) provides detailed information about physical characteristics of lymphedema and whether there is agreement between imaging and clinical data. The study population included 46 women with chronic arm edema after axillary dissection for breast cancer. US showed in each patient an increase of subcutaneous tissue thickness compared with the contralateral arm. Fluid accumulation was seen in 16 patients (34.7%), fibrosis in 12 (26.0%), and a mixed picture (fibrosis and fluid) in 18 (39.1%). Correlation with clinical information ("soft," "medium," "hard, "and "pitting" edema) demonstrated that US documented interstitial fluid in 68.4% of soft edema, mixed fluid and fibrosis in 64.2% of medium edema, and fibrosis in 76.9% of hard edema. Ultrasonography also showed that in soft and medium edema, fibrosis may already have formed. US is useful to follow progression, composition, and management of arm lymphedema after axillary dissection. PMID- 11783593 TI - A retrospective study of the effects of the Lymphapress pump on lymphedema in a pediatric population. AB - We studied the effects of the Lymphapress pump (LP; Global Medical Imports, Digby, NS, Canada) retrospectively on 16 children with primary or secondary lymphedema of the upper or lower extremities by measuring the volume and circumference of the limbs before and after treatment. We reviewed medical charts for data on age, sex, length of disease process, grade of lymphedema, frequency and duration of treatment, and pump pressures used. We recorded changes in limb size before and after pumping in terms of the mean percentage difference between the affected and unaffected limb at both time points to allow for growth of the child and the extremity. On volumetric measures, thirteen (93%) of the subjects showed a clinical trend towards sustained maintenance or reduction in size of the lymphedematous limb(s). The reduction in the pump pressure at start of the treatment to that required to maintain the size of the limb was statistically significant (p = 0.0036). Fourteen (88%) of the subjects had no complications directly attributable to the pump, whereas two had complications that were probably unrelated to LP. Overall, there was a clinical trend towards reduction or maintenance of the lymphedematous limb size in children using LP without notable adverse sequelae. PMID- 11783594 TI - Lymphogenous cyst-vein shunt in the management of chylothorax and chylorrhea. AB - A 36 year-old woman developed marked lymphedema and chylous cysts of the lower abdominal wall, groin, labia, accompanied by chylorrhea. After cyst excision and transplantation of the greater omentum, a left chylothorax occurred. After thoracic duct ligation and left pleurodesis, pleural effusion recurred and worsened. Lymphangioscintigraphy and conventional lymphography suggested that undrained enlarged retroperitoneal lymphatics in the right iliac fossa had disrupted and lymph had leaked into the left chest from the right iliac fossa. Treatment by a lymphatic cyst-vein anastomosis redirected excess chylous lymph into the blood circulation and chylothorax initially remitted. Several years later with recurrence of chylorrhea, the anastomosis was found to be occluded. After a second operative connection between a lymphogenous cyst and the greater saphenous vein, chylorrhea subsided and chylothorax has remitted for more than 4 years. PMID- 11783595 TI - Microlymphatic aneurysms in patients with lipedema. AB - "Lipedema," a special form of obesity syndrome, represents swelling of the legs due to an increase of subcutaneous adipose tissue. In 12 patients with lipedema of the legs and in 12 healthy subjects (controls), fluorescence microlymphography was performed to visualize the lymphatic capillary network at the dorsum of the foot, at the medial ankle, and at the thigh. Microaneurysm of a lymphatic capillary was defined as a segment exceeding at least twice the minimal individual diameter of the lymphatic vessel. In patients with lipedema, the propagation of the fluorescent dye into the superficial lymphatic network of the skin was not different from the control group (p > 0.05). In all 8 patients with lipedema of the thigh, microaneurysms were found at this site (7.9 +/- 4.7 aneurysms per depicted network) and in 10 of the 11 patients with excessive fat involvement of the lower leg, multiple microlymphatic aneurysms were found at the ankle region. Two obese patients showed lymphatic microaneurysms in the unaffected thigh and in only 4 patients were microaneurysms found at the foot. None of the healthy controls exhibited microlymphatic aneurysms at the foot and ankle, but in one control subject a single microaneurysm was detected in the thigh. Multiple microlymphatic aneurysms of lymphatic capillaries are a consistent finding in the affected skin regions of patients with lipedema. Its significance remains to be elucidated although its occurrence appears to be unique to these patients. PMID- 11783596 TI - Measuring lymphatic leukocytes in inflammation. PMID- 11783597 TI - Human afferent lymph contains apoptotic cells and "free" apoptotic DNA fragments- can DNA be reutilized by the lymph node cells? PMID- 11783598 TI - Low protein diets and outcome of renal patients. AB - Protein-restricted diets have been proposed in patients with chronic renal failure (CRF) to correct uremic symptoms and to slow the progression of CRF thus delaying the initiation of dialysis. Questions have been raised about the compliance to such diets, their nutritional safety and efficacy. In two-thirds of selected and motivated patients, satisfactory compliance is observed; however, in the overall predialysis population, compliance is fair and does not exceed 50%. When patients are carefully monitored, protein-restricted diets, rather than inducing malnutrition, may prevent it. Moreover, the outcome of these patients, when treated by dialysis, is not affected by prior dietary prescription. A small but real beneficial effect of low protein diet (LPD) on the rate of progression of CRF is observed in nondiabetic renal diseases, but their beneficial effect seems to be greater in diabetic renal disease. Meta-analyses confirm that LPD can effectively postpone renal replacement therapy by moderately slowing the decline in GFR and also by substantially delaying the onset of uremic symptoms. PMID- 11783599 TI - Clinical course and treatment of IgA nephropathy. AB - Impairment of renal function, severe proteinuria and arterial hypertension are the strongest clinical predictors of an unfavorable outcome in IgA nephropathy (IgAN). Glomerulosclerosis and interstitial fibrosis are the most reliable histologic prognostic markers. Metabolic syndrome and insulin resistance probably affect the clinical course of the disease. Among the known gene polymorphism it seems that there is a link between the ACE gene D allele and the progression of IgAN. Elevated blood pressure should be actively treated. The target blood pressure is 130/80 mmHg or less and the goal should also be to reduce proteinuria. Several large-scale trials are currently testing corticosteroids and other drugs in the treatment of IgAN. PMID- 11783600 TI - Treatment of IgA nephropathy with angiotensin converting enzyme inhibitors: design of a prospective randomized multicenter trial. AB - Although several in vitro studies and clinical observations suggest that ACE inhibitors (ACE-I) are a promising treatment for IgA nephropathy (IgAN), meta analysis of published data is not yet conclusive. Therefore, a European double blinded, prospective, randomized therapeutic trial was designed to evaluate ACE-I treatment benefits in young IgAN patients (<35 years old) with persistent moderate proteinuria (>1<3.5 g/day/1.73 m2) and fair renal function (creatinine clearance >50 mL/min/1.73 m2). Patients enrolled are randomly assigned to benazepril (0.2 mg/kg/day) or placebo. Patients should be enrolled within a five year recruitment period (end on December 2003) for a total duration of follow-up of six years (end on December 2004). Hypertension and some genetic, histological and immunological factors will be evaluated to clarify their eventual role in the final response to ACE-I treatment. PMID- 11783601 TI - Pirfenidone reduces in vitro rat renal fibroblast activation and mitogenesis. AB - BACKGROUND: Fibroblasts have been universally recognised in tubulointerstitial injury, where their presence has been shown to be a marker of disease progression. Recently, pirfenidone (PF) has been shown to both ameliorate progressive fibrosis and reduce established scarring after ureteric obstruction (UUO) in the rat, suggesting that it is a novel anti-fibrotic agent. The objective of this study was therefore to determine if these effects include down regulation of fibroblast function. METHODS: Cortical fibroblasts were obtained from outgrowth cultures of renal tissue isolated from kidneys 3 days after UUO and constituted 100% of cells studied. Functional studies examined the effects of 20 and 200 microg/ml PF on basal serum stimulated activity. Activation was examined by western blotting for alpha smooth muscle actin (alphaSMA) and connective tissue growth factor (CTGF). Cell proliferation, collagenase activity and collagen production were determined from kinetic studies, zymography for MMP2 and [3H] proline incorporation in collagenous proteins respectively. RESULTS: Proliferation, as measured by [3H] thymidine incorporation, was reduced in dose dependent manner by 20 and 200 microg/ml PF (p<0.05; 200 vs 0 microg/ml). Likewise, 200 microg/ml PF reduced cell population growth over 5 days of culture (p<0.05 vs 0 microg/ml). PF (200 microg/ml) decreased alphaSMA and CTGF protein expression to 66+/-13 and 37+/-26% of basal levels respectively (both p<0.05 vs 0 microg/ml). Synthesis of collagen was unaffected by PF. Maximal dose of PF produced a modest reduction in MMP2 lytic activity (p=0.05). Effects of PF were independent of cell toxicity. CONCLUSIONS: Down-regulation of renal fibroblast activation and proliferation are specific actions of PF. PMID- 11783603 TI - Lecithin: cholesterol acyltransfer, dyslipoproteinaemia and membrane lipids in uraemia. AB - BACKGROUND: Dyslipoproteinaemia is the most important complication linked to the increased morbidity and mortality of uraemic patients from cardiovascular disease. Many factors contribute to the dyslipoproteinaemia, including increased production of very low density lipoproteins (VLDL), decreased lipolysis and impaired low density lipoprotein (LDL) receptor activity. In this study, the role of decreased lecithin:cholesterol acyltransferase (LCAT) activity in relation to plasma and membrane lipid changes is examined. METHODS: Fasted blood samples were taken from 65 uraemic patients, including roughly equal numbers of haemodialysis, peritoneal dialysis and undialysed subjects, and from 29 apparently healthy individuals. Plasma total and free cholesterol, cholesteryl esters (CE), total and individual phospholipids, high density lipoprotein (HDL)-, LDL- and VLDL cholesterol were all measured, as were erythrocyte and lymphocyte free cholesterol and phospholipids. RESULTS: More than half of all patients, including those both on haemodialysis and peritoneal dialysis, as well as untreated individuals, had relative plasma concentrations of CE below the normal mean - 2SD. These patients had significantly decreased LDL- (2.62 +/- 1.04 compared to 3.61 +/- 0.97 mmol/L; p < 0.001) and HDL-cholesterol (0.71 +/- 0.30 compared to 0.94 +/- 0.27 mmol/L; p < 0.01) and increased VLDL-cholesterol (0.60 +/- 0.50 compared to 0.47 +/- 0.26 mmol/L; p < 0.05) as well as significant increases in membrane cholesterol and cholesterol/phospholipid molar ratio in erythrocytes (3.30 +/- 0.49 and 0.87 +/- 0.08 compared to 2.95 +/- 0.18 mmol/g wet weight and 0.76 +/- 0.04 mol/mol respectively, both p < 0.001) and cholesterol/phospholipid molar ratio of lymphocytes (0.58 +/- 0.14 compared to 0.45 +/- 0.04 mol/mol; p < 0.001). They were markedly deficient in LCAT activity (56.1 +/- 20.4 compared to 105.5 +/- 17.5 nmol/ml/h; p < 0.001). The LCAT activity in plasma of patients with high CE was higher than for those with low CE, but it was also significantly less than normal and this group showed smaller changes in other lipid parameters. CONCLUSIONS: LCAT deficiency is common in uraemia and is associated with changes not just in plasma lipids, but also in membrane lipids which may be relevant to the progression of the disease. PMID- 11783602 TI - Evidence of a threshold value of glycated hemoglobin to improve the course of renal function in type 2 diabetes with typical diabetic glomerulopathy. AB - We recently observed that the course of glomerular filtration rate (GFR) rapidly declines in a subgroup of Type 2 diabetic patients (D) with abnormalities of albumin excretion rate (AER) and typical diabetic nephropathy, despite tight blood pressure control. The aim of this study was to evaluate whether amelioration of blood glucose control, using insulin, improves the course of GFR. GFR decay was measured by spline modeling analysis of the plasma clearance rate of 51CR-EDTA, assessed every 6 months. We identified two groups of D using morphometric analysis of renal biopsy, who had values of glomerular basement membrane (GBM) and fractional mesangial volume (Vv mes/glom) respectively below (Group A: 38) or above (Group B: 50) the mean+2SD of values found in 27 kidney donors (GBM: 389 nm; Vv mes/glom: 0.25), as previously described in detail. Median AER was similar at base line in the 2 groups (109 microg/min, 29-1950, in Group A, 113 microg/min, 37-1845, in Group B; n.s.). Conventional metabolic therapy (sulphonylureas and/or biguanides) was used both in Group A and B during a 3 year follow-up period (Period 1). Group B was further divided in two subgroups with body mass index below (Group B, a) and above (Group B, b) the value of 30 kg/m2. Mean +/- SD HbA1c was 8.2 +/- 1.6% in Group A, 8.3 +/- 1.7% in Group B (a) (n.s.) and 9.1 +/- 1.7% in Group B (b) (n.s.). Tight blood pressure control was achieved and maintained using angiotensin converting enzyme inhibitors and/or beta blockers and/or calcium antagonists and/or thiazides. The mean arterial blood pressure (MAP) was 92 +/- 3 mmHg in Group A and 91 +/- 4 mmHg in Group B (n.s.). GFR decay was significantly greater in Group B than in Group A (Group A vs B: +1.21 +/- 0.71 vs -5.86 +/- 1.61 ml/min/1.73 m2/year). Median AER significantly rose in Group B (177 microg/min, p<0.05 vs base line) but not in Group A (134 microg/min, n.s.) during the third year of follow-up. Groups A and B were then followed over 4.1 years (range 3.1-4.4) (Period 2) maintaining the above described antihypertensive regimen, resulting in MAP values similar to those described during Period 1. Group A patients were treated with the same conventional glycemic control during Period 2. Group B (a) was conversely treated with intensive insulin therapy to achieve a HbA1c value below 7.5% (3 daily injections of regular and 1 or 2 daily injections of intermediate acting insulin associated with metformin 500 mg twice daily in 64% of the patients). Group B (b) patients were only treated by metformin (850 mg thrice daily) to achieve a HbA1c value below 7.5%. HbA1c decreased below the 7.5% target value in Group B (a) (7.0 +/- 1.6%, p<0.01 vs Period 1), but not in Group B (b) (8.0 +/- 1.6%, p<0.05 vs Period 1) and in Group A (8.3 +/- 1.7%, n.s. vs Period 1). The GFR decay of Group B, a during Period 2 was lower than that during Period 1 (Period 1 vs Period 2: 5.9 +/- 1.8 vs -1.8 +/- 0.7 ml/min/1.73 m2/year, p<0.01). GFR decay during Period 2 was similar to that observed during Period 1 in Group A (Period 1 vs Period 2: +1.21 +/- 0.71 vs +0.7 +/- 0.6 ml/min/1.73 ml/year, n.s.) and in Group B (b) (Period 1 vs Period 2: -4.4 +/- 0.71 vs -4.2 +/- 0.6 ml/min/1.73 m2/year, n.s.). Median AER did not significantly change in the fourth year of Period 2 , either in Group A or B (Group A vs B: 141 vs 152 microg/min, n.s.). In conclusion, our findings seem to suggest that amelioration of blood glucose control is attained both by insulin and metformin intensive treatment, but only insulin decreases and maintains HbA1c levels below 7.5%. These pattens of HbA1c appear to be a threshold value in order to significantly blunt GFR decay in a subgroup of Type 2 diabetic patients with typical diabetic glomerular lesions, who are less responsive to tight blood pressure control alone. Conversely, the cohort of patients with less severe diabetic glomerulopathy steadily show constant GFR patterns, despite similar abnormalities of albumin excretion rate, and HbA1c average values above 7.5%. PMID- 11783604 TI - Continuous urea monitoring in hemodialysis: a model approach to forecast dialytic performance. Results of a multicenter study. AB - BACKGROUND: A urea biosensor, inserted into the ultrafiltrate collection-line of paired filtration dialysis (PFD), not only allows on-line dialysis quantification, but also forecasts final (Cend) and 30 min equilibrated urea concentration (Ceq), the most reliable value for calculating dialysis efficiency. The urea biosensor processes plasma ultrafiltrate continuously, delivering a large amount of data to the computer, which estimates the parameters by a mathematical model, thus predicting the whole urea profile with rebound. METHODS: A multicenter randomized trial on 41 patients was conducted to ascertain the ability of a two-pool variable-volume urea model to forecast Cend and Ceq at 60 and 90 min after the start of dialysis. Two alternative dialytic treatments, A or B, were chosen, the latter being more efficient. Each treatment included six serial PFD. The accuracy of forecasting was evaluated through four indices based on forecast errors, calculated as the difference between observed and forecasted urea values: mean percent error (MPE) (%), mean absolute deviation (MAD) (mg/dl), mean absolute percent error (MAPE) (%) and root mean squared error (RMSE) (mg/dl). RESULTS: Forecasted urea concentrations were lower than those measured by the biosensor. MPE for Cend was negligible in A (+1.2%) and much higher in B (+7.2%); both values improved at 90 min, +1.0% and +5.8%, respectively. MAD for Cend was similar in both treatments and improved slightly at 90 min, ranging from 4.9 to 5.9 mg/dl. MPE for Ceq was +4% in A and and more than doubled in B (+11.5%); both values improved at 90 min, +3.7% and +9.7%, respectively. MAD for Ceq was 7.5 mg/dl in A and 8.5 mg/dl in B; both improved at 90 min, 6.7 and 7.4 m g/dl, respectively. The other indices, MAPE and RMSE, showed similar results. Comparison between the errors of the two treatments with analysis of variance (ANOVA) for repeated measures gave no significant results. CONCLUSIONS: Our model forecasts of urea concentrations were overall lower than the measured ones: the bias was negligible for A-Cend, greater for the A-Ceq and when the more efficient treatment B was used. The 60 min predictions improved at 90 min. The comparison between the prediction errors in the two treatments were not statistically significant. The recirculation measurement would probably reduce the bias if it were properly incorporated into the model. PMID- 11783605 TI - Heart rate response to hemodialysis-induced changes in potassium and calcium levels. AB - BACKGROUND: It is well known that hemodialysis affects cardiovascular functions, mainly because of excess body water removal. Conversely, the role of hemodialysis induced modifications in body fluid characteristics is not yet well-grounded. In particular, the impact of modifications in plasma electrolytes on the pacemaking rhythm of the sinus node has not yet been evaluated. METHODS: Eight patients on regular hemodialysis treatment were studied along a two-hour diffusive dialysis study session without fluid removal. Biochemical (metabolic and hormonal) as well as hemodynamic parameters were measured during the treatment. A computer model of the sinus node cell electrical activity was used to analyse the experimental data. The measured changes in electrolyte concentrations and pH were imposed as model inputs and the model-computed heart rate changes were validated against the measured ones. After validation, numerical simulation was used to obtain a quantitative evaluation of the comparative weight of calcium and potassium on heart rate changes, by simulating treatments leading to different changes in plasma concentrations of such electrolytes. RESULTS: A significant heart rate increase (11%) was obtained following potassium, calcium and pH changes, with no significant variations in indices of autonomic activity. Simulation results revealed that calcium load and potassium removal both accelerate sinoatrial pacemaker beating. Concurrent changes in these electrolyte concentrations may cause heart rate to increase up to 30% at the end of hemodialysis. Heart rate sensitivity to extracellular potassium changes appears to be strictly dependent upon calcium concentration. CONCLUSIONS: Hemodialysis-induced changes in calcium and potassium concentrations may greatly affect the rhythm of the sinus node pacemaker. PMID- 11783606 TI - Takayasu's arteritis: a changing disease. AB - Takayasu's arteritis (TA) is a chronic, giant-cell vasculitis of unknown etiology, which primarily involves the aorta, its main branches and coronary and pulmonary arteries. This review focuses on the epidemiological, diagnostic, and clinical aspects of the disease, which have been changed since the first description made by Mikito Takayasu in 1908. The article also summarizes the data collected by the Italian Registry of TA in the period 1993-1998. PMID- 11783607 TI - Pathogenesis of Takayasu's arteritis. AB - Takayasu's arteritis is an inflammatory disease of the arteries that involves large vessels. The inflammatory lesions in Takayasu's arteritis originate in the vasa vasorum and are followed by cellular infiltration, mainly composed of T cells (gammadelta lymphocytes, cytotoxic T lymphocytes, T helper cells), but also of natural killer cells, dendritic cells, monocytes and granulocytes, invading the outer layer of the media and/or its neighbouring adventitia. At this stage, positive production of inflammatory cytokines and/or adhesion molecules around these areas is remarkable. According to data available--in Takayasu's arteritis- interleukin-6, interleukin-1 and RANTES are released in large amounts by infiltrating inflammatory cells within damaged tissue, as well as by circulating inflammatory cells, and very likely help maintain the aberrant immune activation, by promoting endothelial cells activation and by inducing lymphocyte infiltration. Although the nature of the antigen that triggers the auto-immune process is still unknown, the infiltrating T lymphocytes may recognize one or a few self-antigens processed and presented in association with HLA. A considerable percentage of patients with Takayasu's arteritis have immune complexes in sera; moreover, on peripheral blood lymphocyte, Fc receptors and antibodies reactive against human endothelial cells (AECA) have been detected. This observation raised the possibility that AECA might have a role in endothelial cell activation and expression of adhesion molecules, which will facilitate leukocyte traffic. PMID- 11783608 TI - The role of radiology in the diagnosis and management of Takayasu's arteritis. AB - In the last years new computer-based imaging techniques, like color Doppler sonography, Computed Tomography, and Magnetic Resonance, have allowed a non invasive approach to vascular diseases, partially replacing angiography, and increasing the role of radiology in the diagnosis and management of many chronic diseases, such as Takayasu's arteritis. Simultaneous evaluation of luminal and vascular wall changes may now allow a simpler diagnosis of this condition also in its early phase and the effective therapy monitoring. Application of new procedures of interventional radiolgy provides a safer and more conservative correction of late steno-occlusive complications. Familiarity with the different imaging features of Takayasu arteritis will permit a more accurate clinical diagnosis and management of this insidious disorder. PMID- 11783609 TI - Takayasu's arteritis: therapeutic strategies. AB - Takayasu's arteritis (TA) is a chronic inflammatory disease of unknown origin, primarily affecting the walls of large vessels. TA can be a severe and life threatening disease, and has relevant consequences for the patient's life-style. Mortality and morbidity depend on both the direct effect of the vascular lesions and the following complications. The mainstay of TA therapy is based on the use of glucocorticoids alone or in association with cytotoxic drugs. Unfortunately, in the majority of cases, only a partial control of the disease is obtained. The therapeutic strategy may vary in different countries, and in Japan, where the disease was first described, high dose glucocorticoids are preferred to glucocorticoids in association with cytotoxic agents. We present here a review of the pharmacologic strategies most commonly adopted for the treatment of TA in America, Italy and Japan, together with our experience on 31 TA patients, who have been followed in the last two decades. The discussion is also open on which criteria are more accurate in measuring disease activity. PMID- 11783610 TI - Vascular access for hemodialysis: an indepth review. PMID- 11783611 TI - Markers of progression in IgA nephropathy. PMID- 11783612 TI - Evaluation of trabecular bone orientation in wrists of young volunteers using MR relaxometry and high resolution MRI. PMID- 11783613 TI - Simulation of osteoporosis bone changes: effects on the degree of anisotropy. PMID- 11783614 TI - Changes in bone remodeling rate influence the degree of mineralization of bone which is a determinant of bone strength: therapeutic implications. PMID- 11783615 TI - Synchrotron radiation microCT: a reference tool for the characterization of bone samples. PMID- 11783616 TI - Prediction of distal radius failure with microFE models based on 3d-PQCT scans. PMID- 11783617 TI - Visualization and analysis of trabecular bone architecture in the limited spatial resolution regime of in vivo micro-MRI. PMID- 11783618 TI - The effects of PTH (1-34) on bone structure and strength in ovariectomized monkeys. PMID- 11783619 TI - Experimental measurement of three-dimensional continuum-level strain fields in trabecular bone. PMID- 11783620 TI - Engineering microstructures to evaluate and replace trabecular bone. PMID- 11783621 TI - Micro-FE analyses of bone: state of the art. AB - The ability to provide a complete characterization of elastic properties of bone has vastly improved our understanding of trabecular bone mechanical properties. Based on this information, it was possible to validate several mechanical concepts related to the elastic behavior of trabecular bone that could not be validated earlier. With recently developed micro-CT scanners and the availability of large parallel computer systems, this technique has also enabled the determination of physiological bone tissue loading conditions from very large microFE models that can represent whole human bones in detail. Such analyses can provide the data needed for a better understanding of bone failure processes or cell mediated load adaptive remodeling processes. Computational demands for whole bone analyses, however, are still excessive. Unlike linear stress and strain analyses, the application of PFE to study non-linear processes, in particular bone failure mechanisms, is still in an early phase Results of recent studies, however, are promising and indicate that an accurate prediction of bone failure with these techniques is possible. Compelling features of such analyses are that they enable multi-axial failure criteria at the apparent level to be developed using primarily computational methods as well as that they can provide a basis for detailed analysis of micro-mechanics associated with trabecular failure at the apparent level. The application of microFE techniques to analyze bone in vivo is in an early stage as well. First results have indicated that, although the resolution of presently available in vivo imaging techniques (i.e. pQCT and MR) is much less than that of images used so far for uFE analyses, the technique can provide meaningful elastic properties of trabecular bone in vivo in most cases. It is expected that the remaining uncertainties in the microFE results can be eliminated as soon as the resolution of in vivo images is improved. With the fast developments in pQCT(47) and MR scanning, this will probably be in the near future. PMID- 11783622 TI - In vivo micro tomography. PMID- 11783623 TI - Changes in trabecular bone structure assessed by high-resolution MRI in patients after transplantation. PMID- 11783624 TI - Direct measures of trabecular bone architecture from MR images. PMID- 11783625 TI - Evaluation of mechanical properties of trabecular and cortical bone. PMID- 11783626 TI - Three-dimensional digital topolgical analysis of trabecular bone. PMID- 11783627 TI - Hierarchical structure of bone and micro-computed tomography. AB - Bone is highly complex, with multiple hierarchical levels of structure. Micro-CT has been able to provide much information about the properties of bone at several of these levels at the mid-range of bone's hierarchical structure, and it will continue to provide a valuable tool for further characterizing bone in various conditions and explaining mechanisms of bone failure. PMID- 11783628 TI - Central control of bone mass: brainstorming of the skeleton. PMID- 11783629 TI - Micro-computed tomography to evaluate bone remodeling and mineralization. PMID- 11783630 TI - Assessment of bone quality, quantity, and turnover with multiple methodologies at multiple skeletal sites. PMID- 11783631 TI - Fracture healing and micro architecture. PMID- 11783632 TI - Toxic potency assessment of non- and mono-ortho PCBs, PCDDs, PCDFs, and PAHs in northwest Mediterranean sediments (Catalonia, Spain). AB - Forty-five marine sediments from the Catalonian coast were analyzed for non-ortho and mono-ortho chlorine substituted PCB congeners, PCDDs and PCDFs, and 16 PAHs. Concentrations of total PCBs ranged from 1.1 to 311 ng/g dry weight (d.w.), and the levels of the sum of the 16 PAHs analyzed ranged between 13.4 ng/g d.w. and 16.7 microg/g d.w. The PCB and PAH contamination was greater near the sites of urban and industrial impact. Total toxicity equivalent (TEQ) values were calculated using the toxicity equivalent factors (TEFs) proposed by WHO for dioxin-like PCBs, PCDDs, and PCDFs. These levels ranged between 0.03 and 24.8 pg WHO-TEQ/g d.w. for PCBs and from 0.4 to 39.2 pg WHO-TEQ/g d.w. for PCDDs/PCDFs. Therefore, the suggested sediment quality guideline was sometimes exceeded. Moreover, TEA values were calculated for PAH concentrations, applying different TEFs proposed by the literature. The results obtained were between 0.3 pg TEQ/g d.w. and 18.4 ng TEQ/g d.w. and showed that the TEQ(PCDD/F) and TEQ(PCB) values were several times lower than the TEQ(PAH) values in the marine sediment samples investigated. PMID- 11783633 TI - Atmospheric lifetimes and fates of selected fragrance materials and volatile model compounds. AB - Fragrance materials are semivolatile organic compounds widely used in consumer products. Despite their generally low volatility, it is expected that a fraction of these compounds will volatilize into the atmosphere, where they can photolyze, react with OH radicals, NO3 radicals and O3, and/or undergo wet and dry deposition. Using relative rate methods, rate constants have been measured at 296 +/- 2 K for the gas-phase reactions of OH radicals, NO3 radicals, and 03 with the fragrance materials 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2 naphthalenyl)ethanone (OTNE), acetyl cedrene [(3R-(3a,3ab,7b,8aa))-1 (2,3,4,7,8,8a-hexahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl)ethan-1 one], and HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethycyclopenta-[gamma]-2 benzopyran) as well as with isochroman which is structurally related to HHCB. Measured rate constants (in cm3 molecule(-1) s(-1) units) are OH radical reactions [OTNE, (9.85 +/- 0.88) x 10(-11); acetyl cedrene, (7.7 +/- 1.6) x 10( 11); HHCB, (2.6 +/- 0.6) x 10(-11); and isochroman, (3.7 +/- 0.6) x 10(-11)], NO3 radical reactions [OTNE, (1.71 +/- 0.19) x 10(-11) and acetyl cedrene, (4.1 +/- 1.0) x 10(-15)], and O3 reactions [OTNE, (2.1 +/- 0.5) x 10(-18) and acetyl cedrene, <2.2 x 10(-18)] where the error limits are two least-squares standard deviations. Rate constants for the OH radical reactions predicted by a structure reactivity estimation method agree well with the measured values. The dominant tropospheric loss processes for the compounds studied are calculated to be in a reaction with OH radicals during daytime and, for OTNE and acetyl cedrene, with NO3 radicals during nighttime. The calculated atmospheric lifetimes due to daytime reaction with the OH radical are a few hours or less for the fragrance materials studied and indicate that these specific compounds will not undergo long-range transport in the atmosphere. PMID- 11783634 TI - Dioxin-like PCBs released from waste incineration and their deposition flux. AB - To investigate the formation and decomposition behaviors of dioxin-like PCBs during incineration of municipal solid wastes in a recently constructed facility, the concentrations of dioxin-like PCBs were measured in municipal solid waste before incineration and in the incinerator emission gas and residues. Using these values, release/inflow ratios of dioxin-like PCB congeners (ratio of the amount released from the incinerator to the amount flowing into the incinerator through waste) were calculated. For PCB congeners 126, 169, and 189, these ratios were greater than 1. In contrast, ratios of the other dioxin-like congeners were much less than 1. To take into account atmospheric sources, the amounts of dioxin-like PCBs released via emissions from municipal solid waste incineration were compared with atmospheric depositions in the Kyoto City area. Most of the PCDD/F congeners and homologue groups were deposited in amounts similar to those found in emissions from the waste incinerator. Deposition of dioxin-like PCB congeners 81, 126, 169, and 189 were also found in amounts similar to those released via the waste incinerator emissions. However, depositions of congeners 105, 114, and 118 greatly exceeded the amounts released via waste incinerator emissions. In reviewing the congener profiles of industrial PCB products and emission gas, the following general trends were observed: (i) For congeners whose contents are high in industrial PCB products (e.g., 105 and 118), the amounts deposited were much higher than the amounts released with waste incineration emission gas. (ii) For congeners whose percentages were high in the waste incineration emission gas (e.g., 126 and 189), the amounts deposited were similar to the amounts released in the waste emission gas. PMID- 11783635 TI - Chemical fractionation of metals in wetland sediments: Indiana Dunes National Lakeshore. AB - Tessier-type (1979) sequential extractions for heavy metals (Cd, Cr, Cu, Fe, Mn, Pb, and Zn) were conducted on sediments from two wetland sites, one inundated and the other drained, within the Indiana Dunes National Lakeshore (IDNL), NW Indiana, with the objective of (i) evaluating extraction techniques on organic rich sediments, (ii) determining the geochemistry and mobility of potentially biotoxic trace metals in a contaminated environment, and (iii) considering the implications of different restoration strategies on the potential for heavy metal remobilization. Long and repeated extractions were needed to effectively degrade the organic-rich sediments (up to 75% of the sediment by mass). Analysis of sulfur fractionation revealed that it was predominantly sequestered along with the organically bound fraction (renamed oxidizable). Metal recovery was good with the sum of the extractant steps typically within 20% of the total metal concentration determined after total microwave digestion. Results showed metal fractionation to be both metal- and site-specific, The oxidizable fraction is dominant for Cu, Cr, and Fe (>65% of the nonresidual fraction for almost all samples) and overall is most important also for Cd and Pb. The iron/manganese oxide fraction is important for Pb, Mn, and Zn, particularly at the drained site. The carbonate bound fraction is relatively insignificant at both sites, except for Cd and Mn, although it is more important at the drained site. The exchangeable fraction is significant in the uppermost sediments at the drained site, particularly for Cd (3-24%), Pb (3-14%), and Zn (36-45%); whereas, for the inundated site, it ranged only from 0 to 1% Zn, with no detectable Cd or Pb. Chromium, Cu, and Fe exist in forms not likely to be remobilized, whereas Cd, Mn, Pb, and Zn are potentially mobile if drained wetland sites are reflooded (and pH and redox potential altered). Simple mass balance calculations illustrate the potential for the removal of approximately 84,375 kg of exchangeable Zn if currently drained sites across the IDNL are reflooded, with concentrations in water draining into Lake Michigan as high as 5 ppm. PMID- 11783636 TI - Carbon isotope ratios for chloromethane of biological origin: potential tool in determining biological emissions. AB - Chloromethane (CH3Cl) with a global atmospheric burden of 5.3 million t is the most abundant halocarbon in the atmosphere. However, the origin of ca. 50% of the estimated annual global input of 4 million t of the gas to the atmosphere has yet to be determined. As the oceanic contribution to the global CH3Cl flux is now tightly constrained, an important terrestrial source is either underestimated or unrecognized. It has recently been proposed that higher plants may represent a CH3Cl source of sufficient magnitude to resolve the global budget imbalance. A potentially useful tool in validating CH3Cl emission flux estimates is comparison of the carbon isotope ratio of atmospheric CH3Cl with those of CH3Cl originating from various sources. Here we report the first measurements of delta13C for CH3Cl produced biologically. The CH3Cl released by the higher plant species Batis maritima and Solanum tuberosum was dramatically depleted in 13C with respect to plant tissue (delta13C = -36.8/1000 and -34.5/1000, respectively); CH3Cl released by the fungus Phellinus pomaceus also showed significant 13C depletion with respect to the wood growth substrate (delta13C = -17.9/1000). When reliable delta13C values for the other major sources of atmospheric CH3Cl become available, the distinctive isotopic signature of plant-derived CH3Cl should help constrain the contribution to the atmospheric burden from this source. PMID- 11783637 TI - Identification and quantification of estrogen receptor agonists in wastewater effluents. AB - Total concentrations of several known xenobiotic estrogen receptor (ER) agonists and natural and synthetic estrogen were measured in water by use of a combination of instrumental and bioanalytical approaches. Samples from 3 municipal wastewater treatment plants (WWTPs) in south central Michigan (upstream and effluent); 4 point source locations on the Trenton Channel of the Detroit River, MI; and 5 locations in Lake Mead, NV were analyzed. Organic compounds were extracted from 5 L water samples using solid-phase extraction disks and separated into three fractions based on polarity. Whole extracts and fractions were tested for ER agonist potency using the MVLN in vitro bioassay. ER agonist potency was characterized by comparing the magnitude of induction elicited by the extract or fraction to the maximum induction caused by 17beta-estradiol (E2). The greatest concentrations of ER agonists were associated with the most polar fraction (F3). Instrumental analyses and further fractionation were used to identify specific ER agonists associated with bioassay responses. Bioassay data were compared to extract concentrations in order minimize variability associated with the extraction procedure. Concentrations of endogenous estrogen, E2, and the synthetic estrogen ethynylestradiol (EE2) ranged from nondetectable to 14.6 ng/mL extract (nondetectable to 3.66 ng/L water) and represented from 88 to 99.5% of the total estrogen equivalents in the water samples analyzed. Concentrations of alkylphenols (APs) ranged from nondetectable to 148 microg/mL extract (nondetectable to 37,000 ng/L water). In general, alkylphenols contributed less than 0.5% of the total estrogen equivalents in the water samples. Both bioassay directed fractionation results and comparison of ER agonist concentrations, adjusted for their known relative potencies, support the conclusion that E2 and EE2 were the dominant environmental estrogens in water samples from mid-Michigan and Lake Mead, NV. PMID- 11783638 TI - Characterization of secondary aerosol from the photooxidation of toluene in the presence of NOx and 1-propene. AB - Secondary organic aerosol (SOA) from the photooxidation of toluene in a hydrocarbon-NOx mixture was generated in a 190 m3 outdoor Teflon chamber. The photooxidation reaction of toluene in the gas phase leads to substituted aromatics (TOL-AR), nonaromatic ring retaining (TOL-R), and ring opening products (TOL-RO). In this work, the following ring opening oxycarboxylic acids were newly identified: glyoxylic acid, methylglyoxylic acid, 4-oxo-2-butenoic acid, oxo-C5 alkenoic acids, dioxopentenoic acids, oxo-C7-alkadienoic acids, dioxo-C6-alkenoic acids, hydroxydioxo-C7-alkenoic acids, and hydroxytrioxo-C6-alkanoic acids. The newly characterized TOL-R and TOL-RO products included methylcyclohexenetriones, hydroxymethylcyclohexentriones, 2-hydroxy-3-penten-1,5-dial, hydroxyoxo-C6 alkenals, hydroxy-C5-triones, hydroxydioxo-C7-alkenals, and hydroxy-C6 tetranones. Products in both the gas and aerosol phases were derivatized with O (2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) for carbonyls and pentafluorobenzyl bromide (PFBBr) for carboxylic acid and phenol groups and analyzed using a gas chromatograph/mass spectrometry (GC/MS) in an electron impact mode (EI) and a gas chromatograph/ion trap mass spectrometry (GC/ITMS) in both chemical impact and EI modes. To confirm different isomers, the PFBHA derivatives of products were rederivatized by silylation using N,O bis(trimethylsilyl)trifluoroacetamide (BSTFA). The Fourier transform infrared spectroscope (FTIR) was used to obtain additional functional group information for SOA products impacted on a zinc selenide FTIR disk. The major SOA products under the high NOx conditions of the above experiment included methylnitrophenols, methyldinitrophenols, methylbenzoquinones, methylcyclohexenetriones, 4-oxo-2-butenoic acid, oxo-C5-alkenoic acids, hydroxy C3-diones, hydroxyoxo-C5-alkenals, hydroxyoxo-C6-alkenals, and hydroxydioxo-C7 alkenals. Of the major SOA products, the experimental partitioning coefficients (iKp) of aldehyde products were much higher and deviated more from predicted iKp values. This is an extremely important result, because it shows that aldehyde products can further react through heterogeneous processes, which may be a very significant SOA generation mechanism from the oxidation of aromatics in the atmosphere. PMID- 11783639 TI - Influences of land use on water quality of a diverse New England watershed. AB - Analysis of variations in major ion chemistry in the Mill River watershed reveals the importance of anthropogenic activities in controlling streamwater chemistry. Average concentrations of NO3- and SO4(2-) show a positive correlation with percent catchment area altered by human land uses, and concentrations of Cl- increase with road density. Water removal from municipal reservoirs increases the downstream concentration of NO3- and SO4(2-) over that predicted by land use changes, showing that removal of high quality upstream water concentrates pollutants downstream. In salt-impacted streams, Cl- exceeds Na- by 10-15% due to cation exchange reactions that bind Na+ to soil. The net effect of nonpoint source pollution is to elevate ANC in the most developed areas, which impacts the natural acidity of a large swamp. The sum of base cations (C(B)) exceeds ANC for all samples. Plotting C(B) against ANC and subtracting Cl- quantifies the impact of road salt from the impact of the addition of strong acids. PMID- 11783640 TI - Isolation and partial characterization of dissolved copper-complexing ligands in streamwaters. AB - We have separated two groups of copper-complexing ligands (the weak and strong ligands) from streamwaters in the Lake Biwa watershed by modified immobilized metal ion affinity chromatography (IMAC). The weak ligands were about 0.54-1.21% of the total dissolved organic matter (DOM), as determined by UV absorbance, and the strong ligands were about 0.06-0.21%. The results show that the stronger ligands were retained longer on the IMAC column, eluted later, and were accompanied by shorter wavelength UV absorbers, fluorescence maxima patterns with shorter wavelength excitation, and relatively "fresher" organic matter. The weak ligands with logK'(CuL) values of 6.6-7.7 had predominant humic-like fluorescence and may have been considerably degraded, while stronger ligands with logK'(CuL) values of 8.9-9.3 had only protein-like fluorescence and were relatively newly produced, labile material, as indicated from their amino acid composition. The protein-like fluorescence was mainly due to aromatic tryptophan probably bound to proteins or peptides. The results presented here have significant implications regarding the possible sources and biogeochemical role of organic ligands in aquatic environments. PMID- 11783641 TI - Volatilization of toxaphene from Lakes Michigan and Superior. AB - The pesticide toxaphene was used extensively on cotton in the southern United States until its use was restricted in 1982. It was previously reported that the upper Great Lakes have received toxaphene by gas absorption following long-range transport from the south and are currently saturated with respect to toxaphene. However, the rate of loss of toxaphene from Lakes Michigan and Superior had been estimated using sparse or estimated data, and thus, these estimates had high uncertainties. For this investigation, samples were collected to provide extensive data on air, water, and sediment concentrations of toxaphene for the upper Great Lakes for the period 1997-98. These data were used to calculate the annual and seasonal fluxes of toxaphene from water to air and sediment. Lake Superior is 200-1000% saturated with toxaphene, and Lake Michigan is 200-500% saturated. It seems clear that both lakes will outgas toxaphene into the atmosphere for some considerable time in the future, and Lake Superior, because of its generally lower water temperatures and higher toxaphene concentration, will outgas toxaphene even longer than will Lake Michigan. PMID- 11783642 TI - Effect of ozone on algae as precursors for trihalomethane and haloacetic acid production. AB - The effect of ozone on the trihalomethane (THM) and haloacetic acid (HAA) formation of two algae species was investigated. Scenedesmus quadricauda (green alga) and Cyclotella sp. (diatom) were cultured under controlled conditions and harvested in the log or late log growth phase. Experiments examined the formation of disinfection byproducts (DBPs) from the algal suspensions with and without preozonation. Preozonation with 1 mg/L increased chloroform formation from Scenedesmus by 17-44%. For Cyclotella, chloroform production increased by 5-26% with 1 mg/L ozone and by 39-109% with 3 mg/L ozone. Chlorinated HAA yields were not significantly increased after 1 mg/L ozone but increased by 38-76% for Cyclotella after 3 mg/L ozone. As compared to other sources of organic matter, algae under bloom conditions may contribute significantly to the DBP precursor pool. However, the majority of the DBP precursors (70%) were attributable to the cellular material, and thus removal of algae cells from a drinking water supply priorto oxidation will substantially reduce algal precursor concentrations. PMID- 11783643 TI - Sorption of antimony onto hydroxyapatite. AB - We prepared synthetic hydroxyapatite [HAP; Ca5(PO4)(3-x)(CO3)x(OH)(1+x) (x = 0.3)] and then investigated this material's ability to remove trivalent antimony [Sb(III)] from water. The HAP was characterized by X-ray diffraction analysis, scanning electron microscopy, X-ray energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy. The sorption of Sb(III) to HAP was measured over an Sb(III) concentration range of 0.05-50 mg L(-1), at constant ionic strength (I = 0.01 mol dm(-3)) in equilibrated aqueous suspensions (34 g dm(-3)) for 5 < pH < 8 in vessels that were closed to the atmosphere. Under these conditions, we found that HAP particles were enriched in Ca after incongruent dissolution of the solid. More than 95% of the Sb(III) in solution adsorbed to the solid-phase HAP in <30 min. The equilibrium distribution of Sb(III) (solid vs liquid phase) was characterized by a Langmuir model with gamma(max) = 6.7 +/- 0.1 x 10(-8) mol m(-2) (1.4 +/- 0.2 x 10(-4) mol dm(-3) g( 1)) and K(ads) = 1.5 +/- 0.2 x 10(3) dm3 mol(-1). As Sb adsorption occurred, the pH of the isoelectric point (pH(iep)) of the HAP suspensions declined from 7.7 to 6.9. This finding supports the idea that the negative surface potential of the HAP increased due to the adsorption of Sb as a charged species. The decline in pH(iep) during Sb adsorption plus the thermodynamic description of the Sb(III) HAP-H2O system suggest likely surface reactions for the interaction of Sb with HAP. We discuss the efficiency of Sb removal from water by HAP in the context of phosphate enrichment. PMID- 11783644 TI - Microbial populations associated with the reduction and enhanced mobilization of arsenic in mine tailings. AB - Microbial reduction of arsenate [As(V)] to arsenite [As(III)] and the subsequent effects on As mobilization in contaminated mine tailings were studied under transport conditions. Molecular analysis of bacterial populations and traditional isolation techniques were used in conjunction with column experiments designed to observe relationships among pH (limed vs unlimed treatments), redox potential (Pt electrode), and mobilization of As. Liming increased pH values from approximately 4 to 8, resulting in a 5-fold increase in total As eluted from sterile columns. Elution of As from limed columns was further enhanced by microbial activity. As(III) was the predominant As species eluted from oxic, nonsterile columns. Conversely, in sterile treatments, As(V) was the predominant valence state in column effluent. Denaturing gradient gel electrophoresis coupled with sequence and phylogenetic analysis of 16S rRNA gene segments revealed that liming of the mine tailings stimulated specific Caulobacter-, Sphingomonas-, and Rhizobium-like populations. Pure culture isolates of these bacteria demonstrated the ability to rapidly reduce As(V) in aerated serum bottles. An intracellular As detoxification pathway was implicated in the reduction of As(V) by these isolates. These results indicate that microbial reduction of As(V) in As-contaminated soils may occur under aerobic conditions over relatively short time scales resulting in enhanced As mobilization. PMID- 11783645 TI - Degradation characteristics of humic acid during photo-Fenton processes. AB - Changes in the molecular and structural characteristics of humic acid (HA) during photo-Fenton processes were studied. When aqueous solutions at pH 5.0, which contained HA, Fe(III), and H2O2, were irradiated (lambda > 370 nm), the concentrations of total organic carbon (TOC) decreased with increasing irradiation time, indicating that a portion of the HA was mineralized to CO2 during this process. To investigate the changes in molecular and structural characteristics, the HA was reisolated from the reaction mixtures after each period of irradiation. The increased elution volumes required for isolation by gel permeation chromatography indicated that the molecular size of HA decreased as a result of the irradiation. In the FTIR spectra, ether and epoxide functional groups were identified, after irradiation. These products could be formed via radical coupling and/or via peroxy radical addition reactions to the unsaturated groups in the HA, such as vinyl and aromatic groups. Moreover, an analysis of structural fragments in HA by pyrolysis-GC/MS showed that the cinnamic acid moieties (CA) disappeared, as a result of irradiation. In the molecular weight fractionated HA, the majority of the iron species were complexed with the high molecular weight HA fraction, and the CA levels of the high molecular weight fraction were larger than those in the low molecular weight fraction. These results are consistent with residues, as the reactive sites in the photo-Fenton systems. Therefore, the degradation of these sites in the high molecular weight fraction may serve as a factor in decreasing the molecular size of HA. PMID- 11783646 TI - Time-resolved laser fluorescence spectroscopy study of the sorption of Cm(III) onto smectite and kaolinite. AB - For long-term performance assessment of nuclear waste repositories knowledge concerning interactions of actinides with mineral surfaces is imperative. The mobility and bioavailability of released radionuclides is strongly dependent on sorption/desorption processes onto mineral surfaces. Therefore it is necessary to characterize the surface species formed and to elucidate the reaction mechanisms involved. The high fluorescence spectroscopic sensitivity of Cm(III) has attracted our interest regarding the complexation process of Cm(III) onto smectite and kaolinite as a model system for the sorption of trivalent actinides in the trace concentration range. We conclude that at low pH Cm(III) is sorbed onto kaolinite and smectite as an outer-sphere complex and retains its complete primary hydration sphere. With increasing pH inner-sphere adsorption onto kaolinite and smectite occurs via the aluminol edge sites. The same evolution of the Cm(III)-clay surface species as a function of pH was observed for both minerals. Starting at a pH > or = 5 we observe the formation of a [triple bond]Al O-Cm2+(H2O)5 surface complex, which is replaced by a second species at higher pH. The second surface complex may be a monodentate [triple bond]Al-O-Cm+(OH)(H2O)4 species or bidentate [triple bond](Al-O)2-Cm+(H2O)5 species. The Cm(III)/clay surface complexes are characterized bytheir emission spectra (peak maxima at 598.8 and 603.3 nm) and their fluorescence lifetime (both 110 +/- 7 micros). An important result in view of the mobility and bioavailability of radionuclides is that no incorporation of Cm(III) into the bulk clay structure was observed. PMID- 11783647 TI - Degradation of 4-nonylphenol in homogeneous and nonhomogeneous mixtures of soil and sewage sludge. AB - Sewage sludge is frequently applied as fertilizers to cultivated land. However, municipal sewage sludge often contains organic contaminants including nonylphenol (NP), an intermediate from nonionic surfactant degradation. Knowledge about NP degradation in sludge-amended soil is an important prerequisite for adequate risk assessments. In this study, mineralization of 14C-labeled NP in homogenized and nonhomogenized sludge-soil mixtures was investigated. NP was degraded within 38 days in aerobic homogenized mixtures. In nonhomogeneous mixtures containing sludge aggregates, the degradation of NP was retarded and was generally not completed within 3 months (119-126 days). No detectable amounts of NP were transported from the sludge aggregates to the surrounding soil (detection limit: <0.04 mg of NP/kg dw of soil). Oxygen penetration into sludge aggregates was monitored for 50 days with an oxygen microelectrode. An extrapolation of the oxygen data suggested that more than 1 year was required to obtain fully aerobic conditions in a 2-cm sludge aggregate. Since NP is considered persistent in the absence of oxygen, residual amounts of NP may be present in the anaerobic center of aggregates for prolonged periods. The results demonstrate that sludge aggregate size and thus oxygen availability will be a major controlling factor for NP degradation in soil amended with sewage sludge and that the mobility of NP from sludge aggregates to the surrounding soil is negligible. PMID- 11783648 TI - Kinetic modeling of homogeneous mercury oxidation: the importance of NO and H2O in predicting oxidation in coal-derived systems. AB - This paper develops and evaluates an elementary reaction mechanism for homogeneous Hg0 oxidation that accounts for major interactions among Cl-species and other pollutants in coal-derived exhausts. Most importantly, interactions among NO and Cl-species were found to exert a strong and previously unrecognized impact on homogeneous Hg0 oxidation under some but not all conditions. The proposed oxidation mechanism is subjected to quantitative evaluations against all the available laboratory datasets that characterize homogeneous Hg0 oxidation when HCl is the primary chlorinated species. The simulations depict the reported extents of oxidation for broad ranges of HCl and temperature within useful quantitative tolerances without any heuristic parameter adjustments. The predicted pool of Cl-atoms was found to be governed by the chemistries of moist CO oxidation, Cl-species transformations, and NO production. However, an artificial initiation scheme was needed to depict the temperature dependence observed in one set of literature data. This indicates that either the kinetic mechanisms are incomplete or that heterogeneous initiation came into play under these test conditions. The evaluations further show that Hg oxidation is primarily through a Cl atom recycle process, with Cl and Cl2 concentrations both playing an important role. Oxygen weakly promotes homogeneous Hg oxidation, whereas moisture is a stronger inhibitor. NO can promote or inhibit homogeneous Hg oxidation, depending on its concentration. In the presence of NO, extents of Hg oxidation increased for progressively faster quenching. Conversely, without NO, extents of oxidation diminished for faster quenching. PMID- 11783649 TI - Artificial aging of phenanthrene in porous silicas using supercritical carbon dioxide. AB - Expedited artificial aging is described and demonstrated using a novel system that circulates a solution of supercritical carbon dioxide and a hydrophobic organic sorbate (phenanthrene) through a closed loop containing a porous substrate. Unlike traditional methods used to simulate the natural aging process, our approach allows for real-time monitoring of sorption equilibria, and the process is highly accelerated due to the unique physical properties of supercritcal carbon dioxide. The effectiveness of the system to simulate aging was demonstrated with a series of experiments in which three silicas with varying particle and pore sizes were loaded with phenanthrene. Batch aqueous desorption experiments were used to evaluate the extent of the aging process. For the two types of particles containing the largest pores (i.e., mean diameters of 202 and 66 A), 95% and 86%, respectively, of the phenanthrene was released to the aqueous fraction within 3 h. In contrast, only 16% of the phenanthrene was released from particles having a mean pore diameter of 21 A after 24 h. These results were confirmed by the results from an aqueous column desorption experiment. Confounding factors that might contribute to slow aqueous desorption such as the hydration state of the particles' surfaces, the chemical form of the loaded phenanthrene, and the organic carbon content were investigated and/or normalized for all three particle types. Consequently, we were able to attribute the slow desorption behavior and the presence of the resistant fraction in the 21 A silica to pore effects. With properly designed experiments, the results of this study suggest that the supercritical fluid system could be extended to the study of contaminant aging and bioavailability in natural soils and sediments. PMID- 11783650 TI - Synergistic effect of cationic surfactants on perchloroethylene degradation by zero-valent iron. AB - Zero-valent iron (ZVI) as a permeable barrier material for degradation of chlorinated organic compounds has been extensively studied recently. One of the focal areas in ZVI studies is to increase the contaminant reduction rate. In this research, batch tests were performed to evaluate the synergistic effect of sorbed cationic surfactants on degradation of perchloroethylene (PCE). Sorption of cationic surfactants on ZVI was a function of hydrophobic chain length of the surfactanttail group. Minimal counterion sorption indicated that the sorbed surfactant molecules form a patchy monolayer on ZVI. Both PCE and trichloroethylene (TCE) degradation by ZVI with and without sorbed surfactant followed pseudo-first-order reaction kinetics. In general, the PCE degradation rate increases as the chain length of sorbed surfactant increases. Compared to unmodified ZVI, both apparent rate constants of PCE degradation and TCE accumulation increased by an order of magnitude when ZVI was modified by hexadecyltrimethylammonium. The rate of PCE degradation by ZVI modified to lower surfactant loading was relatively higher than that by ZVI modified to higher surfactant loading. It was speculated that longer chain length will result in better admicelle formations, and thus, promote PCE partition and increase PCE surface concentration or surface admicelle catalysis, while low surfactant loading makes significant amounts of surface reduction sites still available. The PCE reduction rate constants were not affected by solution ionic strength, but high initial solution pH, buffered by sodium carbonate and sodium bicarbonate, significantly reduced the PCE degradation rate. PMID- 11783651 TI - Modeling the long-term frequency distribution of regional ozone concentrations using synthetic meteorology. AB - A new method is developed to generate the meteorological input fields required for use with photochemical airshed models that seek to predict the effect of pollutant emissions on the long-term frequency distribution of peak O3 concentrations. Instead of using meteorological fields derived from interpolation of direct weather observations, this method uses synthetically generated meteorological data. These synthetic meteorological fields are created by first constructing a semi-Markov process that generates a time series of large-scale synoptic weather conditions that statistically resemble the occurrence and persistence of synoptic weather patterns during specific months of the year. Then for each day within each synoptic weather category, local weather variables indicative of the meteorological potential for ozone formation are drawn from the approximated joint distribution of the summation of three pressure gradients across the airshed and the 850 mb temperature measured in the early morning. The synthetic initial conditions are combined with boundary values that are extracted from historical days that match the chosen synoptic class, temperature, and pressure gradient values as closely as possible for use in a prognostic mesoscale meteorological model. The prognostic mesoscale meteorological model generates the meteorological input fields necessary for the photochemical airshed model. The airshed model driven by synthetically generated meteorological data is executed for a 31 day period that statistically resembles weather during the month of August in Southern California using pollutant emissions data from the year 1987. The procedure produced a frequency of occurrence of peak 8 h average ozone concentrations that compared well both to that produced by the deterministic model as well as to the O3 concentrations observed over the August months of the years 1984-1990. PMID- 11783652 TI - Integrated exposure and dose modeling and analysis system. 3. Deposition of inhaled particles in the human respiratory tract. AB - Detailed information on the composition-resolved size distribution of particulate matter deposited along the human respiratory tract can help linking epidemiological, toxicological, and pathological studies and thus potentially improve the understanding of the origin of pulmonary disorders induced by respirable pathogens. For this purpose, a new mechanistic dosimetry model describing the dynamics of respirable particles in the human airways was developed. Model predictions of transport and fate of inhaled aerosols are based on solutions of the aerosol general dynamic equation, which describes changes in particle size and mass distributions resulting from processes such as nucleation, condensation, coagulation, gas phase chemical reaction, and deposition. To compensate for approximating the three-dimensional problem by considering only axial variations along the airways, boundary layer effects are introduced via appropriate dimensionless transport parameters. The architecture of the human lung is described by Weibel's simple regular dichotomous model. An important advantage of the present approach is that it allows testing the significance of intersubject lung morphology and ventilation variability for particle deposition and dose calculations. The model predicts the evolution of size and composition distributions of inhaled particles and the deposition profile along the human lower respiratory tract: in general, model predictions are in qualitative and quantitative agreement with tracheobronchial and alveolar deposition data. PMID- 11783653 TI - Multicomponent remote sensing of vehicle exhaust by dispersive absorption spectroscopy. 2. Direct on-road ammonia measurements. AB - Remote sensing was employed for the first time to measure NH3 levels in the exhaust of on-road light duty motor vehicles. The sensor also measured the concentration of CO2, CO, hydrocarbons, and NO, among other pollutants, in the emitted exhaust. Field measurements were conducted at a Los Angeles freeway on ramp; vehicles traveled at cruise speeds between 20 and 25 m s(-1) (45-55 mi h( 1)). Mean fleet NH3 levels of 44.7 +/- 4.1 ppm were observed. These emissions exhibited a highly skewed distribution: 50.1% of the emitted NH3 was contributed by 10% of the sampled fleet. The pollutant distribution among high NH3 emitters is analyzed to identify the conditions that lead to three-way catalyst malfunction and, hence, NH3 formation. In contradiction with previous reports, we found that high NH3 emissions could not be attributed to vehicles running under rich air-fuel conditions. We estimate a mean fleet NH3 mass emission rate of 667 +/- 57 mg L(-1) (Er = 94 +/- 8 mg km(-1)). These findings could have significant implications on air quality in the South Coast Air Basin (SoCAB) of California, since they support the hypothesis that emissions from motor vehicles constitute a dominant regional source of NH3, between 20 and 27% of total daily emissions. As NH3 is the predominant atmospheric base, tropospheric levels play a key role in the buffering capacity of the atmosphere and, hence, the formation of fine aerosol. Our results could explain the ubiquitous distribution of ammonium fine particles observed during fall stagnation conditions in the SoCAB. PMID- 11783654 TI - Polyoxymethylene solid phase extraction as a partitioning method for hydrophobic organic chemicals in sediment and soot. AB - During the past few years, the presence of soot in sediments has received growing interest. Soot is thought to serve as a strong partitioning medium for specific organic contaminants (PAHs). The precise extent of sorption to this material, however, is poorly known because soot/water distribution coefficients for native PAHs have not been determined yet. Measuring these coefficients using existing partitioning methods is problematic due to the nature of soot. Therefore, the objective of this study was to develop a method for the determination of distribution coefficients for organic contaminants in soot/water (but also sediment/water) systems. The method is based on solid phase extraction (SPE) of chemicals onto the plastic polyoxymethylene (POM). Sorption experiments with POM showed monophasic sorption kinetics, linear isotherms covering several orders of magnitude, and a linear relationship between distribution coefficients for POM and the octanol/water distribution coefficient. Therefore, the sorption process can be considered to be true partitioning. Application of POM for the determination of distribution coefficients for soot and sediment (POM-SPE method) resulted in highly reproducible values. The method was validated by comparing values for sediment with results for the same sediment determined using the cosolvent method. This comparison resulted in an almost 1:1 relationship, proving the method's validity. PMID- 11783655 TI - Synthesis of polybrominated diphenyl ethers and their capacity to induce CYP1A by the Ah receptor mediated pathway. AB - Polybrominated diphenyl ethers (PBDEs) have become widely distributed as environmental contaminants due to their use as flame retardants. Their structural similarity to other halogenated aromatic pollutants has led to speculation that they might share toxicological properties such as hepatic enzyme induction. In this work we synthesized a number of PBDE congeners, studied their affinity for rat hepatic Ah receptor through competitive binding assays, and determined their ability to induce hepatic cytochrome P-450 enzymes by means of EROD (ethoxyresorufin-O-deethylase) assays in human, rat, chick, and rainbow trout cells. Both pure PBDE congeners and commercial PBDE mixtures had Ah receptor binding affinities 10(-2)-10(-5) times that of 2,3,7,8-tetrachlorodibenzo-p dioxin. In contrast with polychlorinated biphenyls, Ah receptor binding affinities of PBDEs could not be related to the planarity of the molecule, possibly because the large size of the bromine atoms expands the Ah receptor's binding site. EROD activities of the PBDE congeners followed a similar rank order in all cells. Some congeners, notably PBDE 85, did not follow the usual trend in which strength of Ah receptor binding affinity paralleled P-450 induction potency. Use of the gel retardation assay with a synthetic oligonucleotide indicated that in these cases the liganded Ah receptor failed to bind to the DNA recognition sequence. PMID- 11783656 TI - Monitoring of phthalic acid monoesters in river water by solid-phase extraction and GC-MS determination. AB - An analytical method for monitoring 10 phthalic acid monoesters in river water was investigated by solid-phase extraction, methylation with diazomethane, and GC MS. Two cartridge-type solid phases packed with octadesyl-coated silica (C18) and styrenedivinyl polymer (PS-2) and one disk-type solid phase made from octadesyl coated styrenedivinylbenzene polymer (SDB-XD) were investigated in solid-phase extraction. PS-2 gave the highest recoveries of the three solid phases, and recoveries of more than 80% of the monoesters in filtered water samples were obtained at pH 2 to 3 with PS-2 at the spiked level of 0.1 microg L(-1), except for monomethyl-phthalate (MMP), in which more than 72% of the monoesters were recovered. For the monoesters in the suspended solids (SS), an acidic methanol extract of SS was added to purified water acidified to pH 2, and the monoesters were extracted with PS-2. The recoveries of the monoesters in SS were more than 80%, but the recoveries of MMP were more than 57%. The method detection limit (MDL) of each phthalic acid monoester in 500 mL of water sample and in 2 mg of dry weight of SS ranged from 0.010 to 0.030 microg L(-1) and from 1 to 11 microg g(-1), respectively. Monitoring of phthalic acid monoesters in the Tama River in Tokyo was conducted every month from March 1999 to February 2000 using the present method. MMP, mono-n-butyl-phthalate (MBP), and mono-(2-ethylhexyl) phthalate (MEHP) were detected at concentrations of 0.030-0.0340, 0.010-0.480, and 0.010-1.30 microg L(-1), respectively, in the filtered water samples but were not detected in SS. Dimethyl-phthalate (DMP), di-n-butyl-phthalate (DBP), and di (2-ethylhexyl)-phthalate (DEHP) were detected in the river water at concentrations of 0.010-0.092, 0.008-0.540, and 0.013-3.60 microg L(-1), respectively. Diethyl-, di-iso-butyl-, and benzylbutyl-phthalates were also detected at concentrations of nanograms per liter, whereas the corresponding monoesters did not appear. The concentrations of MBP and MEHP in the river water were slightly lower than those of the corresponding diesters at the majority of sampling sites and sampling times. PMID- 11783657 TI - The development of iodine based impinger solutions for the efficient capture of Hg0 using direct injection nebulization-inductively coupled plasma mass spectrometry analysis. AB - Inductively coupled plasma mass spectrometry (ICP/MS) with direct injection nebulization (DIN) was used to evaluate novel impinger solution compositions capable of capturing elemental mercury (Hg0) in EPA Method 5 type sampling. An iodine based impinger solution proved to be very efficient for Hg0 capture and was amenable to direct analysis by DIN-ICP/MS. Hg0 capture efficiency using aqueous iodine (I3-) was comparable to Hg0 capture using acidified potassium permanganate impinger solutions which were analyzed by cold vapor atomic absorption spectrometry (CVAAS), with greater than 98% capture of Hg0 in the first oxidizing impinger. Using DIN-ICP/MS, it was demonstrated for the first time that iodine can be generated just prior to impinger sampling for efficiently oxidizing Hg0 and retaining it in solution as HgI4(2-). Due to the increased interest in Hg speciation from combustion sources and the potential for using DIN ICP/MS for multiple metals analyses, an impinger sampling train for gaseous Hg speciation and multiple metals analyses using DIN-ICP/MS analyses is presented. The unique feature of such a sampling train is that each impinger solution in the series is amenable to direct analysis by DIN-ICP/MS. A bituminous coal was combusted in a bench scale coal system, and gaseous Hg species (oxidized and elemental) were determined using the proposed impinger train. The DIN-ICP/MS instrumental detection limit was 0.003 ppb, and MDLs ranged from 0.007 to 0.116 microg/L (ppb) in a variety of impinger solutions used for Hg capture. PMID- 11783658 TI - Filtration artifacts caused by overloading membrane filters. AB - The conventional practice of using 0.45 or 0.40 microm membranes to distinguish between the particulate and dissolved phases in natural waters neglects the importance of colloids. Many of the colloids in natural waters pass through 0.45 or 0.40 microm membranes, but a significant fraction at the upper end of the colloidal particle size range is retained. Membrane clogging during filtration decreases the effective pore size and can cause the retention of increasing amounts of colloids. This filtration artifact can cause serious errors in sampling and in assigning trace metals to various particle size classes. We evaluated the effect of membrane loading for two common membrane types (0.45 microm Millipore Durapore and 0.40 microm Nuclepore) on the retention of colloidal Fe, Al, Mn, and OM in three Connecticut rivers. In addition, we used a 1.0 microm Nuclepore membrane to estimate the amount of colloids in the 0.40-1.0 microm size fraction that are retained by membranes during conventional filtration. All samples were collected with clean techniques, and all filtrations were carried out in a class 100 clean room. A peristaltic pump, set at an initial flow rate of 120 mL/min, was used to pump samples through 47 mm diameter inline Teflon filter holders. Back pressure and flow rate were monitored during filtration, and both are good indicators for the onset of membrane clogging. The results show a consistent correlation between increasing back pressure and decreasing concentration of colloidal Fe and sometimes Al, Mn, and OM in the filtrate for all membrane types. Although the shape of the loading-retention curves varied dramatically by site and by membrane type, the essential relationship between back pressure, flow rate, and filtration artifacts during membrane clogging remained the same. PMID- 11783659 TI - Dense medium plasma environments: a new approach for the disinfection of water. AB - The levels to which microbial colony forming units are permitted in various waters fit for human contact are carefully regulated. Conventional chemical and physical approaches usually are complex processes with significant limitations due to the generation of toxic side-products. In this contribution a novel plasma reactor--dense medium plasma reactor--is described, and its efficiency for the disinfection of contaminated water is discussed. It has been shown that owing to the intense stirring of the reaction medium (e.g. contaminated water), as a result of the specially designed spinning electrode and gas-flow system, a volume character discharge is created, which can efficiently kill bacteria. It has been demonstrated that treatment times as low as 20 s are enough for the total inactivation of microorganisms for 200 mL of 10(5) bacteria/mL contaminated water. PMID- 11783660 TI - Biomass byproducts for the remediation of wastewaters contaminated with toxic metals. AB - Pollution of the environment with toxic metals is widespread and often involves large volumes of wastewater. Remediation strategies must be designed to support high throughput while keeping costs to a minimum. Biosorption is presented as an alternative to traditional physicochemical means for removing toxic metals from wastewater. We have investigated the metal binding qualities of two biomass byproducts that are commercially available in quantity and at low cost, namely "spillage", a dried yeast and plant mixture from the production of ethanol from corn, and ground corn cobs used in animal feeds. The biomass materials effectively removed toxic metals, such as Cu, Cs, Mo, Ni, Pb, and Zn, even in the presence of competing metals likely to be found in sulfide mine tailing ponds. The effectiveness of these biosorbents was demonstrated using samples from the Berkeley Pit in Montana. Investigations included column chromatography and slurry systems, and linear distribution coefficients are presented. X-ray spectroscopy was used to identify the binding sites for metals adsorbed to the spillage material. The results of our experiments demonstrate that the biosorption of metals from wastewaters using biomass byproducts is a viable and cost-effective technology that should be included in process evaluations. PMID- 11783661 TI - Reductive dechlorination of tetrachloroethylene in soils by Fe(II)-based degradative solidification/stabilization. AB - Fe(II)-based degradative solidification/stabilization (DS/S) is a modification of conventional solidification/stabilization (S/S) that uses Fe(II) as a reducing agent for chlorinated organics while immobilizing inorganic contaminants. Feasibility of the Fe(II)-based DS/S technology in treating soils contaminated with tetrachloroethylene (PCE) was tested in this study. The results of the PCE degradation experiments conducted in the presence of a humic acid suggest that natural organic matter would not significantly interfere with the degradative reaction by the Fe(II)-containing reactive species in DS/S systems. Solid-phase degradation experiments showed that the DS/S technology could effectively treat PCE in soils without substantial production of chlorinated intermediates. A pseudo-first-order rate law reasonably described degradation kinetics. The half lives of PCE ranged from 13 to 335 days, which are within time spans allowable for typical in-situ DS/S application. Trichloroethylene (TCE) was the only chlorinated product observed in the solid-phase experiments, and its presence was generally transitory with the amount being less than 7% of the initial amount of PCE on a molar basis. A surface reaction appears to control observed PCE degradation kinetics rather than mass transfer to the reactive surface. PMID- 11783662 TI - Formation of chloropyromorphite in a lead-contaminated soil amended with hydroxyapatite. AB - Conversion of soil Pb to pyromorphite [Pb5(PO4)3Cl] was evaluated by reacting a Pb contaminated soil collected adjacent to a historical smelter with hydroxyapatite [Ca5(PO4)3OH]. In a dialysis experiment where the soil and hydroxyapatite solids were placed in separate dialysis bags suspended in 0.01 M NaNO3 solution a crystalline precipitate, identified as chloropyromorphite, formed on the dialysis membrane containing the soil. The aqueous composition of the solution indicated that dissolution of solid-phase soil Pb was the rate limiting step for pyromorphite formation. Addition of hydroxyapatite to the soil caused a decrease in each of the first four fractions of sequential extractable Pb and a 35% increase in the recalcitrant extraction residue. After a 240-d incubation at field-moisture content there was a further increase in the recalcitrant extraction residue fraction of the hydroxyapatite-amended soil to 45% of the total soil Pb. The increase in the extraction residue fraction in the hydroxyapatite amended 0-d incubated soil as compared to the control soil illustrates that the chemical extraction procedure itself caused changes in extractability. Thus, the chemical extraction procedure cannot easily be utilized to confirm changes occurring in amended soils. The further increase after the 240 d incubation implies that the reaction also occurs in the soil during incubation. Extended X-ray absorption fine structure (EXAFS) spectroscopy indicated that after the 240-d incubation the hydroxyapatite treatment caused a change in the average, local molecular bonding environment of soil Pb. Low-temperature EXAFS spectra (chi data and radial structure functions--RSFs) showed a high degree of similarity between the chemical extraction residue and synthetic pyromorphite, providing additional evidence that the change of soil Pb to pyromorphite is possible by simple amendments of hydroxyapatite to soil. PMID- 11783664 TI - Real risks: the need for health leadership and security. PMID- 11783663 TI - Persistence of the insecticide Dimilin 45 ODC on conifer forest foliage in an Atlantic-climate ecosystem. AB - The oil formulation of diflubenzuron (Dimilin 45 ODC) persisted for 10-12 weeks on the foliage of a conifer forest in an Atlantic-climate ecosystem. Within 22-30 days following treatment, 55-80% of the insecticide had been removed from the foliage. During this period, the concentration of diflubenzuron was higher than 370 ng g(-1). Aerial application at 56.3 g of Al ha(-1) resulted in deposition levels of the insecticide ranging from 867.5 to 1824.4 ng g(-1), depending upon forest characteristics. The results showed that aerial application is only a suitable technique for the treatment of forest areas with dense foliage and/or high tree density and no more than 15% of tree-free area. The only metabolite detected was 2,6-difluorobenzamide, and this persisted on foliage until the first rainfalls occurred. An empirical mathematical correlation was found to express the influence of meteorological variables--rainfall, solar radiation and temperature--on the persistence of the insecticide. These results suggested that degradation of diflubenzuron on foliage could be due to photodegradation. Some recommendations were made to optimize the deposition of the insecticide on foliage and to minimize its persistence and the off-site spray drift. PMID- 11783665 TI - Campaign exposure and interpersonal communication as factors in contraceptive use in Bolivia. AB - Two mass media campaigns concerning reproductive health were broadcast in Bolivia from March 1994 to June 1996. Data were collected at three time points from both cross-sectional and panel samples of randomly selected, married, urban women. Campaign exposure and interpersonal communication with spouse, friends, and others were associated with contraceptive knowledge and use, but not attitudes. Campaign exposure was associated with perceptions that members of one's personal network used contraception. This study provides a more contextual view of campaign effects by linking mass media and personal network communication. PMID- 11783666 TI - Relational control in difficult physician-patient encounters: negotiating treatment for pain. AB - Many physicians report feelings of frustration and anger resulting from encounters with patients during which there is disagreement over the use of narcotics to treat pain. In this article, investigators report a relational control analysis of transcripts of three encounters of this type in order to explore the control dimension of these interactions. Similar analyses in the literature have reported that patients in general attempt to gain control of the interaction more often than previously thought. Results of this analysis, however, were remarkable in that nearly half of the transactions were characterized by competition for control. In addition, a descriptive analysis of the control-gaining strategies revealed physician strategies of giving instructions and orders, explicitly rejecting or disagreeing, providing reasons, and attempting to negotiate; patient strategies included explicitly rejecting or disagreeing and providing reasons. Communication skills training may enhance physicians' ability to understand their feelings of discomfort in this type of interaction as well as train them to be more effective communicators during interactions in which there is a struggle for control. PMID- 11783667 TI - Addressing cultural orientations in fear appeals: promoting AIDS-protective behaviors among Mexican immigrant and African American adolescents and American and Taiwanese college students. AB - Fear appeals threatening the individual have been shown to be powerful persuasive devices in the cultures where they have been studied. However, most fear appeal research has been conducted with members of individualist cultures. Individualist cultures place self-needs above group concerns, while collectivist cultures place group needs above self-concerns. Little is known about the effectiveness of fear appeals (or other persuasive strategies) in collectivist cultures. Two studies assessed the effectiveness of AIDS-prevention fear appeals threatening the self versus fear appeals threatening the group (i.e., family) on members of individualist and collectivist cultures. The first study focuses on African American and Mexican immigrant junior high school youth. The second study focuses on U.S. and Taiwanese college undergraduates. The results indicated that fear appeals should address cultural orientation (i.e., individualist versus collectivist orientation) to achieve maximum effectiveness. The results also indicate that one cannot assume cultural orientation based on ethnicity. PMID- 11783668 TI - Doctors' beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention. AB - AIMS: To assess the attitudes of Australian doctors towards the use of antithrombotic drug therapy for stroke prevention in patients with non-valvular atrial fibrillation (AF), and investigate the barriers to prescribing warfarin. METHODS: A postal survey was undertaken among approximately 10% of all registered general practitioners (GPs), cardiologists and physicians in Australia. The anonymous questionnaire used case scenarios to assess doctors' knowledge of current guidelines for the therapeutic management of AF and sought opinions on potential barriers to the use of anticoagulation. RESULTS: Completed questionnaires were received from 711 doctors (30% response rate). The GPs performed better than the cardiologists and other specialists in estimating the risk of stroke in case scenarios. However, the cardiologists were more likely to select the recommended treatment, with GPs being more hesitant to use anticoagulation and tending to underestimate its reported benefit for stroke prevention in non-valvular AF. The GPs were also more likely to overestimate the reported risk of major bleeds with warfarin. In contrast, over one-third of the cardiologists went as far as to give warfarin to a low-risk patient and they were more likely to overestimate the reported benefit of aspirin and warfarin in AF. Only half the doctors correctly classified a patient without a previous stroke (but with other risk factors) as being at high risk. Increased experience as a registered medical practitioner was generally related to a poorer performance on classifying patients according to the risk of stroke. The principal barriers to the use of anticoagulation were nominated as: (i) active gastrointestinal bleeding, (ii) previous intracranial haemorrhage, (iii) alcoholism, (iv) a history of daily falls, (v) liver disease, (vi) severe anaemia and (vii) concurrent use of non-steroidal anti-inflammatory drugs. CONCLUSION: There is scope for improvement in doctors' knowledge about the appropriate use of antithrombotic drug therapy in non-valvular AF and awareness of the results of recent clinical trials. Compilation and dissemination of clear guidelines and focused education on some of the other risk factors (apart from previous stroke or transient ischaemic attacks) in patients with non-valvular PMID- 11783669 TI - Outcome of a smoking cessation programme run in a routine hospital setting. AB - BACKGROUND: Although tobacco smoking remains the largest preventable cause of mortality in Australia, resources to assist with cessation remain scarce. Research studies have demonstrated improved cessation rates with interventions such as counselling and pharmacotherapy, but there is little information on success in routine clinical practice. AIMS: To determine the outcome of a smoking cessation programme run in a routine hospital outpatient setting. METHODS: A prospective audit of patients referred to an outpatient smoking cessation programme by hospital specialists or general practitioners. The programme consisted of fortnightly counselling sessions, with nicotine replacement therapy when clinically indicated. Self-reported abstinence rates were determined by contacting patients by letter or telephone at 3 and 12 months. Abstinence was confirmed, whenever possible, by measuring the expired carbon monoxide (CO) concentration. RESULTS: Over 12 months, 226 new patients were seen through the programme. There was a correlation between the number of cigarettes smoked and the baseline Fagerstrom score (r = 0.49, P < 0.001). Approximately 40% of subjects could not be contacted for follow up. At 3 months the self-reported abstinence rate was 31%, falling to 19% by 12 months. Measurement of expired CO concentrations proved that self-reported abstinence was reliable. CONCLUSIONS: The abstinence rates achieved by our programme compared well with those previously reported in the literature, demonstrating the effectiveness of a smoking cessation programme run in routine clinical practice. There was an increasing relapse rate during the period of follow up. PMID- 11783671 TI - Why do we need clinical practice improvement? A medical perspective. PMID- 11783670 TI - Cost comparison of at-home treatment of deep venous thrombosis with low molecular weight heparin to inpatient treatment with unfractionated heparin. AB - AIMS: Low molecular weight heparins (LMWH) permit safe and effective treatment of uncomplicated deep venous thrombosis (DVT) at home. The aim of this study was to evaluate the cost minimization, cost shifting and patient satisfaction associated with at-home DVT treatment using the LMWH enoxaparin, compared to standard inpatient care in an Australian health-care setting. METHODS: Subjects presenting with a principal diagnosis of uncomplicated DVT to the Emergency Department at The Queen Elizabeth Hospital, Adelaide, were recruited over 1997-1999. Costs to the hospital, to Federal funding (Medicare) and to patients were tracked prospectively, and satisfaction was also measured. Subjects were matched to historical controls (1994-1997) for age, gender and level of comorbidity (same or lower) by two medical officers who were blinded to costs. Control costs were obtained using the clinical costing system Trendstar, and adjusted for consumer price index. RESULTS: Twenty-eight subjects participated in the at-home programme. Of these, 26 were discharged without any inpatient admission (including one who agreed to self-injection) and two were admitted briefly. Audit demonstrated that only 29% of eligible subjects were managed at home. Mean (SEM) total treatment cost was $756 (76) per patient for at-home, and $2,208 (146) for controls. Minimal cost shifts to patients and to Medicare occurred, and satisfaction was high. CONCLUSIONS: At-home treatment of uncomplicated DVT using enoxaparin in an Australian metropolitan setting provides effective cost minimization, with little cost-shifting. Our cost minimisation estimates are conservative as most at-home subjects received enoxaparin twice daily (now used once per day) and controls had at least as high comorbidity. However, uptake of the at-home programme was limited. PMID- 11783672 TI - Changing roles and challenges faced by women in medical specialties. PMID- 11783673 TI - Tobacco control in Australia: bullseye on the wrong target. PMID- 11783674 TI - Spondyloarthropathies: an overview. AB - Spondyloarthropathies are important and common inflammatory arthropathies that occur in approximately 2% of the population. They are often underrecognized. The diagnosis features the presence of asymmetrical, predominately lower limb arthritis and/or inflammatory back pain. The spondyloarthropathies can be subdivided into several disease subcategories, including ankylosing spondylitis, Reiter's/reactive arthritis, psoriatic arthritis, inflammatory bowel disease associated arthritis and a large group of undifferentiated spondyloarthritis. The interactions between infectious agents and the individual's genetic background are important aetiological factors. Therapies for these conditions include physical therapy, non-steroidal anti-inflammatories and disease-modifying drugs. PMID- 11783675 TI - Immunoproliferative small intestinal disease, two cases in the Northern Territory. PMID- 11783676 TI - Gastroesophageal cancer, palmar fasciitis and a matrix metalloproteinase inhibitor. PMID- 11783677 TI - Severe diabetic retinopathy: a rare complication of acromegaly. PMID- 11783678 TI - Junior doctors, prescribing resources and the Australian Medicines Handbook. PMID- 11783679 TI - Bone markers in patients with multiple myeloma and monoclonal gammopathy of undetermined significance. PMID- 11783680 TI - Smallpox and Australia. PMID- 11783681 TI - Feasibility study of the early detection and treatment of renal disease by mass screening. AB - AIM: To determine whether mass screening for proteinuria may be worthwhile in the detection of early renal disease in Australians. METHODS: A feasibility study was conducted using systematic review, meta-analysis and cost-effectiveness methods. RESULTS: End-stage renal disease (ESRD) develops in about 1500 Australians each year. Of these, about 1000 are over 50 years of age (an incidence of about 200 per million, per year). Proteinuria, which is present in about 5% of the general population, confers an approximately 15-fold increased risk for ESRD. Twelve randomized trials of angiotensin-converting enzyme inhibitors (ACEi), in 1943 patients with varying degrees of renal impairment, hypertension and proteinuria, showed that the risk of developing ESRD can be reduced by about 30% over a 2- to 3-year period. In a general-practice-based screening model involving: (i) an opportunistic single dipstick test for protein, (ii) a confirming 24-h urine test for protein and (iii) commencement of ACEi in appropriate individuals, 20 000 people over 50 years of age would need to be screened to prevent one case of ESRD. To achieve this, approximately 100 people would need to be treated with ACEi for 2 to 3 years, and 1,000 would need to have a 24-h urine protein test (and of these, 700 would be false positives). Such a strategy may save health dollars but some critical research questions are still unanswered. What is an individual's risk of developing ESRD, given values for proteinuria, blood pressure and renal function? What is the benefit of ACEi in screen-detected cases, which are at low risk of ESRD? What psychological and physical harm is caused by screening, including the specific renal investigations and treatments that follow on from proteinuria detection? CONCLUSIONS: Given available data, screening middle-aged and older Australians for proteinuria and treating some with ACEi is, at best, a promising primary prevention strategy for preventing ESRD. However, a large population-based cohort study, with nested trial of ACEi, is still required to evaluate whether this model of screening for renal disease does more harm than good. PMID- 11783682 TI - Evidence-based practice: new opportunities, new responsibilities. PMID- 11783683 TI - Preventing perinatal transmission of HIV: an evidence-based update for midwives. AB - This article presents an update on human immunodeficiency virus care in the United States, with an emphasis on care during pregnancy and strategies to prevent perinatal transmission. Common drug regimens are reviewed. Obstetric factors related to transmission, such as mode of delivery, also are discussed. Guidelines for collaboration between midwives and human immunodeficiency virus specialists are outlined. PMID- 11783684 TI - Monitoring the fetus in labor: evidence to support the methods. AB - Electronic fetal monitoring (EFM) was implemented across the United States in the 1970s. By 1998, it was used in 84% of all U.S. births, regardless of whether the primary caregiver was a physician or a midwife. Numerous randomized trials have agreed that continuous EFM in labor increases the operative delivery rate, without clear benefit to the baby. Intermittent auscultation (IA) is safe and effective in low-risk pregnancies and may play a role in helping birth remain normal. Clinicians and educators are encouraged to reconsider the use of IA in the care of healthy childbearing women. PMID- 11783685 TI - Labor and delivery nurses' attitudes toward intermittent fetal monitoring. AB - Fetal monitoring is a routine procedure overseen by labor and delivery nurses and upon which they exert considerable influence. There is a discrepancy, however, between the type of fetal monitoring routinely used and the evidence provided by current research and professional organization recommendations. This study provides the first look at labor and delivery nurses' attitudes toward fetal monitoring in more than 20 years. A descriptive, correlational study was conducted at five southeastern Michigan hospitals to evaluate attitudes toward intermittent fetal monitoring and the effect of selected demographic variables on their attitudes. Of the labor and delivery nurses who participated (N = 145), 72.4% agreed that intermittent fetal monitoring should be the standard of care. Although 87% of the respondents stated that they were willing to provide intermittent monitoring, 53.9% indicated that nurse/patient ratios were a problem in providing this service. Nurses' attitudes were significantly influenced by education level (P = .004), and 48% were unsure about current research findings related to intermittent auscultation. Nurses have a positive attitude toward intermittent monitoring, although safe nurse/patient ratios and clear policies need to be addressed. Lack of knowledge regarding the current evidence and other barriers may contribute to intermittent auscultation not being used routinely, despite the fact that its use for women of low obstetrical risk is supported by current research and professional organizations. PMID- 11783686 TI - Management of the third stage of labor: an evidence-based approach. AB - The third stage of labor usually is eclipsed by the excitement of the birth of a baby. Evidence shows that management of this stage can directly influence important maternal outcomes such as blood loss, need for manual removal of the placenta, and postpartum hemorrhage. Most of the large trials have compared active management of the third stage to expectant management. Active management includes routine use of cord traction and uterotonins, whereas expectant management can be characterized as one of watchful waiting. The use of herbal therapies and homeopathic remedies lack study; additional factors such as site of birth and hydrotherapy also remain to be explored. However, on the basis of current evidence, if a decrease in postpartum bleeding or avoidance of manual removal is desired, an active approach to third stage is the one that should be adopted until and unless contradictory findings are published. PMID- 11783687 TI - Perineal trauma: prevention and treatment. AB - This article examines two aspects of routine midwifery practice: management of the perineum at the end of the second stage of labor and management and repair of perineal injury. Although some aspects of perineal management and repair have been researched and there is reliable evidence on which to base practice, there remains a considerable and urgent collaborative clinical research agenda that midwives should actively pursue. PMID- 11783688 TI - Current best evidence: a review of the literature on umbilical cord clamping. AB - Immediate clamping of the umbilical cord can reduce the red blood cells an infant receives at birth by more than 50%, resulting in potential short-term and long term neonatal problems. Cord clamping studies from 1980 to 2001 were reviewed. Five hundred thirty-one term infants in the nine identified randomized and nonrandomized studies experienced late clamping, ranging from 3 minutes to cessation of pulsations, without symptoms of polycythemia or significant hyperbilirubinemia. Higher red blood cell flow to vital organs in the first week was noted, and term infants had less anemia at 2 months and increased duration of early breastfeeding. In seven randomized trials of preterm infants, benefits associated with delayed clamping in these infants included higher hematocrit and hemoglobin levels, blood pressure, and blood volume, with better cardiopulmonary adaptation and fewer days of oxygen and ventilation and fewer transfusions needed. For both term and preterm infants, few, if any, risks were associated with delayed cord clamping. Longitudinal studies of infants with immediate and delayed cord clamping are needed. PMID- 11783689 TI - An evidence-based approach to male circumcision: what do we know? AB - Midwives care for women throughout their childbearing years, guiding them through decisions made about themselves and their newborn children. The decision to circumcise a male infant depends on a number of factors, including medical, social, cultural, and religious considerations. Data surrounding medical benefits and risks of this surgery are inconsistent and, therefore, confusing. However, substantial data exist to support the conclusions that uncircumcised males have greater incidences of urinary tract infections, especially in the first 6 months of life when complications are greatest, greater incidences of ulcerative sexually transmitted infections, and increased transmission of human immunodeficiency virus. This article reviews available research on the medical benefits and risks of infant circumcision. Informed consent is essential for all parents who must make this decision. PMID- 11783690 TI - Midwifery management of breastfeeding: using the evidence. AB - Strong evidence supports breastfeeding as the appropriate health choice for both mothers and infants. However, the mechanics of breastfeeding are frequently less well understood. This review of both the research and clinical evidence regarding appropriate breastfeeding management is designed to aid the midwife and other health care professionals in providing care and teaching, which will optimize maternal and infant health. PMID- 11783691 TI - Bacteremia due to Leptotrichia trevisanii sp. nov. AB - A thin, filamentous, non-motile, aerotolerant, anaerobic, gram-negative bacterium was isolated from the blood of a 46-year-old man who was diagnosed as having acute myeloid leukemia. The organism had a positive catalase reaction but was negative in indole and oxidase tests. A commercially available system failed to identify the bacterium, but 16S rRNA gene sequencing showed it to be most closely related (97% similarity) to a recently isolated Leptotrichia sp. The DNA base composition was 29.7% mol G+C, and the organism produced lactate as the sole end product of glucose fermentation. These data indicate the isolate is a new species of Leptotrichia for which the name Leptotrichia trevisanii sp. nov. is proposed. PMID- 11783692 TI - Pre- and in-hospital management of community-acquired pneumonia in southern France, 1998-99. AB - A prospective, hospital-based, multicenter study was undertaken to identify the reasons for hospital admission, to describe antibiotic treatment before and during hospitalization, and to determine the outcome of community-acquired pneumonia (CAP). Data collected included prehospital management of CAP, Pneumonia Outcome Research Team (PORT) classification on admission, in-hospital antibiotic treatment, and predictors of death within 30 days. Among the 215 patients (mean age, 66.7 years; M:F ratio, 1.1) recruited, 24 (11.2%) were living in nursing homes. CAP had been diagnosed prior to admission in 55 (25.6%) patients. At admission, 75 (34.9%) patients had a low risk of death (PORT classification I II). A pathogen was isolated for 55 (25.6%) patients, primarily Streptococcus pneumoniae (n=18), atypical agents (n=16), influenza virus (n=10), and respiratory syncytial virus (n=4). Amoxicillin (with or without clavulanate), cefotaxime, or ceftriaxone monotherapy was prescribed to 121 (56.3%) patients. Dual combination therapy was prescribed to patients at higher risk of death (PORT classification III-V; OR, 3.09). Mortality was 7%. Logistic-regression analysis identified nursing-home residency (OR, 8.36), serum creatinine > or =88 micromol/l (OR, 7.88), and Pneumonia Outcome Research Team classification (OR, 1.02) as independent predictors of death. CAP remains a serious disease for elderly persons living in nursing homes. This population should benefit from immunization with pneumococcal and influenza vaccines. PMID- 11783693 TI - Predicting tuberculosis among HIV-infected patients admitted to hospital: comparison of a model with clinical judgment of infectious disease specialists. AB - The aim of this prospective study was to compare a model based on clinical variables with the clinical judgment of infectious disease specialists to identify HIV-infected patients requiring isolation at admission in order to prevent the nosocomial transmission of tuberculosis. Clinical, epidemiological and radiological variables available at admission were recorded for 362 admissions of 274 HIV-infected patients. Using multiple logistic regression analysis, a model to identify patients with tuberculosis was developed based on four clinical variables (node enlargement, constitutional symptoms, intravenous drug use, history of previous correct therapy for tuberculosis) and a positive auramine sputum stain. This model was applied to each of the 362 admissions studied. The decision made by the infectious disease specialist at admission was also recorded. The results indicate that application of the model would have allowed physicians to correctly identify and isolate 24 of 27 patients with tuberculosis, while 5.4 patients without tuberculosis would have been unnecessarily isolated for every patient with tuberculosis. The results for the infectious disease specialists were slightly better, with 26 of 27 patients with tuberculosis being identified and isolated correctly and only 3.2 patients being isolated unnecessarily for every patient with tuberculosis. Thus, a simple model based on clinical variables may be useful in helping physicians identify tuberculosis carriers among HIV-infected patients, but infectious disease specialists are able to identify them more efficiently. PMID- 11783694 TI - Control of nosocomial multiresistant Enterobacteriaceae using a temporary restrictive antibiotic agent policy. AB - An observational study on the epidemiology of multiresistant Enterobacteriaceae was conducted in the neurology and neurosurgery wards of a university hospital to determine the impact of hospital hygiene measures and an additional temporary restrictive antibiotic agent policy on the sudden rise in incidence of these bacteria. The incidence and prevalence of patients with multiresistant Enterobacteriaceae were assessed, and patient isolates were typed phenotypically and by random amplified polymorphic DNA analysis. All hospital hygiene measures implemented were recorded, and the influence of the restrictive policy on antibiotic use was analyzed. This policy consisted of a prior authorization requirement and the withdrawal of all antibiotics with a possible selective pressure on multiresistant strains (gentamicin, tobramycin, quinolones, cotrimoxazole, broad-spectrum penicillins, and cephalosporins). This ban left only carbapenems and amikacin for treatment. Typing showed that 17 of the 61 (28%) patients involved were infected or colonized with a single multiresistant strain of Klebsiella oxytoca, for which an environmental source was identified. The isolates recovered from the other patients comprised eight different species, and subsequent genotyping yielded a great variety of strains. The increased incidence could not be controlled with hospital hygiene measures alone. Only after implementation of the restrictive antibiotic policy did the epidemic strain vanish and the endemic incidence of multiresistant Enterobacteriaceae decrease to <50% of the level before intervention. In the years since, the incidence has remained at this low level, and the antibiotic costs have decreased to a level lower than before intervention. PMID- 11783695 TI - Sabin type 2 polioviruses with intertypic vaccine/vaccine recombinant genomes. AB - Attenuated strains of the Sabin oral poliovirus vaccine replicate in the human gut and, in rare cases, cause vaccine-associated paralytic poliomyelitis. In the present study, 15 vaccine-derived strains isolated from patients with vaccine associated paralytic poliomyelitis and from healthy vaccinees were examined. Four distant sequences of the poliovirus genome (5' NCR, VP3/VP1, VP1/2A, and 3DPol/3' NCR) were targeted, and the reverse-transcribed segments were amplified by polymerase chain reaction followed by restriction fragment length polymorphism analysis with four restriction enzymes. Among the 15 isolates (11 Sabin type 2, 3 Sabin type 1, and 1 Sabin type 3), four Sabin type 2 isolates (36%) were found to be intertypic vaccine/vaccine recombinant in the 3DPol/3' NCR region of the viral genome. The recombinant genotypes identified were S2/S2/S1 for two isolates and S2/S2/S2/S3 and S2/S2/S1/S2 for each of the other two isolates, respectively. Recombinant viruses with unmodified segments in the 5' NCR and the VP3/VP1 regions of the viral genome, a modified segment in the VPI/2A region only for one strain, and an often recombinant segment in the 3DPol/3' NCR parts of the genome were so identified. These findings provide strong evidence that recombination is a frequent phenomenon in type 2 poliovirus vaccine strains and suggest that recombination may be an important mechanism of the natural evolution of polioviruses of Sabin type 2 origin, perhaps even one of the mechanisms of reversion of attenuated vaccine strains toward neurovirulence. PMID- 11783696 TI - Phase I clinical trial with HIV-1 gp160 plasmid vaccine in HIV-1-infected asymptomatic subjects. AB - The aim of the study was to investigate the safety of an HIV-1 gp160 plasmid vaccine. Four asymptomatic HIV-1-infected subjects with CD4+ lymphocyte counts >500/microl were injected with four times 400 microg of HIV-1 modified gp160 env and rev coding DNA vaccine at 0, 4, 10 and 28 weeks. Safety parameters, including autoimmune antibodies as well as CD4+/CD8+ cell counts and HIV-1 plasma concentrations, were monitored for 52 weeks after the first vaccine application. Follow-up data for more than 3 years are now available. The DNA vaccine proved to be safe and, specifically, did not induce anti-DNA autoimmune antibodies. Vaccination had no long-term effects on the CD4+/CD8+ lymphocyte counts, plasma HIV-1 RNA concentrations or disease progression. The present data supplement published data from Philadelphia, USA, where a dose-escalating study (30-300 microg) with the same HIV-1 DNA vaccine was performed. PMID- 11783697 TI - Ceftazidime- and imipenem-induced endotoxin release during treatment of gram negative infections. AB - To determine whether ceftazidime and imipenem, which target two different penicillin-binding proteins, result in different amounts of endotoxin and cytokine release in patients with gram-negative infection, plasma endotoxin, interleukin-6, and tumor necrosis factor alpha were measured during the first 24 h of antibiotic therapy in 27 patients with gram-negative infection who had been randomized to receive either ceftazidime 2 g t.i.d. (n=12) or imipenem/cilastatin 1 g t.i.d. (n=15). The source of infection was the digestive tract (n=13), the urinary tract (n=5), the respiratory tract (n=2), soft tissue (n=2), i.v. line (n=2), or other (n=3). After the first antibiotic injection, a significant increase in the median concentration of plasma interleukin-6 and plasma tumor necrosis factor alpha was noted, without significant differences related to the antibiotic administered. Antibiotic-induced endotoxemia was detectable in nine patients (including 7 with bacteremia). In conclusion, ceftazidime and imipenem had similar effects on endotoxin and cytokine release during the treatment of gram-negative infections. PMID- 11783698 TI - Unusual nosocomial transmission of Mycobacterium tuberculosis. AB - This case report describes how a late diagnosis of a tuberculous abscess combined with daily irrigation of the wound without barrier precautions led to nosocomial transmission of Mycobacterium tuberculosis. Among 372 hospital contacts, 16 had a tuberculin skin test conversion and two developed active pulmonary tuberculosis with the same strain as that isolated from the index patient's abscess. When a culture from an abscess remains negative, Mycobacterium tuberculosis infection should be considered. Furthermore, wound irrigation should be done with proper barrier precautions because infectious aerosols can be created during the irrigation process. PMID- 11783699 TI - Fatal Aspergillus fumigatus Myositis in an immunocompetent patient. AB - A 69-year old farmer developed Aspergillus myositis in the right psoas and paravertebral muscles extending to the retroperitoneum and the fifth lumbar vertebra. The infection appeared after two local instillations of steroid for back pain. Although the patient was not immunocompromised, surgical drainage and antifungal therapy failed to cure him; he died of a bacterial pulmonary superinfection while cultures of the abscess drainage fluid grew Aspergillus. The likely portal of entry in this patient was direct inoculation during infiltration of the steroid; the steroid probably caused a local impairment in host defenses. Only six cases of Aspergillus myositis have been reported previously. All of them occurred in severely immunosuppressed patients and the outcome was fatal in all cases. PMID- 11783700 TI - Comparative in vitro potency of gemifloxacin and fluoroquinolones against recent European clinical isolates from a global surveillance study. AB - Gemifloxacin, a new fluoroquinolone with enhanced activity against gram-positive aerobes, was compared to ciprofloxacin, levofloxacin and ofloxacin against 21,464 recent isolates from 16 European countries. Gemifloxacin was the most potent fluoroquinolone against streptococci including penicillin-, macrolide- and ciprofloxacin-resistant Streptococcus pneumoniae, Staphylococcus aureus, coagulase-negative staphylococci, Acinetobacter spp., Haemophilus spp. and Moraxella catarrhalis. This drug was more potent than or comparable to ciprofloxacin against members of the family Enterobacteriaceae, Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Gemifloxacin is a promising fluoroquinolone with potent in vitro activity. PMID- 11783701 TI - European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. AB - A multicentre in vitro survey was carried out in 1998 in 22 European centres in order to assess the variation in the prevalence of Helicobacter pylori resistance. The susceptibility of 1,274 isolates to metronidazole, clarithromycin and amoxicillin was determined by the E test. The mean rate of resistance to metronidazole was 33.1% (95% CI, 7.5-58.9), to clarithromycin 9.9% (95% CI, 0 28.1) and to amoxicillin 0.8% (95% CI, 0-8.9). Resistance to metronidazole was significantly higher in females (P<0.001), while resistance to clarithromycin was significantly higher in children and teens (P<0.05). Resistance to both agents also tended to be higher in strains isolated from patients from southern European countries than in those isolated from patients from central or northern Europe. Overall, these results emphasize the need for further surveys of Helicobacter pylori sensitivity to antibiotics at a national and regional level. PMID- 11783702 TI - Penicillin-susceptible and erythromycin-resistant Streptococcus pneumoniae in children with acute mastoiditis. AB - Resistance to erythromycin is usually associated with resistance to penicillin in Streptococcus pneumoniae isolates. Over the last few years, however, an increase has been detected in the number of Streptococcus pneumoniae isolates obtained from children with acute otitis media complicated by acute mastoiditis. These isolates are characterized by a penicillin-susceptible and erythromycin-resistant antibiotic profile. This observation prompted a review of the microbiology database and analysis of all Streptococcus pneumoniae isolates with this peculiar antibiotic profile at a university hospital in Madrid, Spain. PMID- 11783703 TI - Treatment options for Streptococcus pneumoniae strains resistant to macrolides, tetracycline, quinolones, or trimethoprim/sulfamethoxazole. PMID- 11783704 TI - Retrospective analysis of early-onset neonatal sepsis in very low birth-weight infants. PMID- 11783705 TI - Retrospective analysis of severe intraventricular hemorrhage and early-onset neonatal sepsis in very low birth-weight infants. PMID- 11783706 TI - Early-stage elephantiasis in bancroftian filariasis. PMID- 11783707 TI - Invasive group B streptococcal disease in nonpregnant adults. PMID- 11783708 TI - Evaluation of a rapid immunochromatographic assay for detection of Streptococcus pneumoniae antigen in urine samples. PMID- 11783709 TI - XML-based visualization of design and completeness in medical databases. AB - PURPOSE: mdplot (medical database plot) visualizes both structure and quality of data in medical databases by means of a summary representation of design and completeness in XML format. The goal is to identify attributes suitable for evaluation and to aid in creating open data models. METHODS: A three-stage visualization approach is applied. First, an overview of all classes in a database, second a detailed view of a specific class and third an analysis of individual attributes. Missing data is identified to enable specific efforts to improve data quality prior to analysis. For each class number of patients, attributes, and records per patient are provided. A condensed bar chart for each category of attributes (categorical, numerical, text and other) visualizes available content: The abscissa corresponds to the sequence of attributes; the ordinate represents completeness per attribute. By selection of a specific class, a detailed description is provided including mean completeness in each category as well as completeness per attribute. To analyse attributes that are collected at several time points per patient, a frequency distribution of records per patient can be generated. RESULTS: The new methodology was applied to two clinical research databases consisting of 292 attributes (955 patients) and 224 attributes (610 patients), respectively, and resulted in major restructuring of the systems. A public website is provided for generation of mdplots. PMID- 11783710 TI - Teleophthalmology link between a primary health care centre and a reference hospital. AB - We have evaluated a teleophthalmology service linking a primary health care centre and an eye clinic at a reference hospital. General practitioners at the primary care centre serving a population of 15,000 and ophthalmologists at the reference hospital participated in this study. Eye fundus digital images were taken from 278 eye fundi of 139 consecutive patients with clinical conditions that could potentially produce fundus alterations. Fundus images were obtained with a non-mydriatic fundus camera (Canon CR6-45M) and were electronically sent reference hospital where ophthalmologist inspected the images and returned the diagnosis. In 18 patients (13%) the images did not have good enough quality to exclude eye fundus lesions. In 24 patients (17%) clear eye fundus alterations were found in at least one eye. In 14 patients (10%) there were image features suggesting retinal alterations that could not be confirmed by image inspection. Media opacity (13 eyes, 5%, seven patients, 5%) was the most common cause of poor image quality. The most difficult assessment was the evaluation of optic nerve head cupping. Retinal oedema was not observable in the digital images. In our experience teleopthalmology services seem to be an effective alternative for eye fundus diagnosis and patient follow-up. PMID- 11783711 TI - Technical aspects of internet-based knowledge presentation in radiotherapy. AB - Three-dimensional radiotherapy planning is a complex and time-consuming optimization process which requires much experience. To simplify and to speed up the process of treatment planning as well as to exchange experience and therapeutic knowledge, the department of Medical Physics at the German Cancer Research Centre (DKFZ) in Heidelberg is developing an Internet-based 3D Radiotherapy planning and Information System (IRIS). IRIS designed internet-based client-server application, implemented using Java, CORBA and PVM. The concept of IRIS combines the functionality of an interactive tutorial with a discussion forum, teleconferencing tool and an atlas of dose distributions. Furthermore an integral knowledge-based system provides automatically generated, preoptimized treatment plans. This paper explains the technical design of the system and gives an overview of experiences gained by the technical realization of a first prototype using currently available internet technology. The prototype is currently running for testing in the intranet of DKFZ. PMID- 11783712 TI - Using the Internet to teach parents and children about constipation and encopresis. AB - Since 1995, we have maintained a tutorial about chronic childhood constipation and encopresis on our web site. The tutorial is directed at parents and older children and includes a feedback form comprised of six multiple-choice questions and a free-text comment field. Between 1 January 1998 and 30 April 2000, we received 1,142 completed feedback forms. The vast majority of respondents identified themselves as parents or guardians of a child with constipation or encopresis. All respondents felt the tutorial was clear and easy to understand. 98% of respondents felt the tutorial helped them understand why children develop constipation and/or encopresis and 91% of respondents felt the tutorial made them better able to take care of a child suffering from constipation and/or encopresis. More than 99% of respondents felt this type of tutorial was a good way to teach people about health problems. 74% of respondents sent us comments about the tutorial. Most often, the comments expressed thanks for having this information available in clear and understandable language, however a significant number of people inquired about a particular child's difficulties or asked a general question not clearly pertaining to a particular child. The results of this study indicate that many people are searching the Internet for information concerning childhood encopresis and that the World Wide Web can provide families with useful information about this common paediatric problem. PMID- 11783713 TI - DTDs go XML schema--a tools perspective. AB - Document Type Definitions (DTDs) are widely used to describe the structure of XML documents. The Clinical Document Architecture (CDA) and the Guideline Element Model (GEM) are examples from the healthcare domain. XML schemas provide another way to describe types of XML documents. In this paper we aim to advocate XML schemas from the perspective of an ANSI standard, the XML based CDA from HL7 (ANSI/HL7 CDA R1.0-2000). It turned out that existing tools do not fully exploit the knowledge contained in DTDs and XML schemas. The result of this study is a set of tools (DTD to XML Schema translator, DTD and XML schema browser, XML editor), which can be downloaded from the official W3C site and which work with any DTD and XML schema. PMID- 11783714 TI - A web-based database for diagnosis of haematologic neoplasms using immunophenotyping by flow cytometry. AB - The interpretation of immunophenotyping results by flow cytometry involves pattern recognition of different haematologic neoplasms that may have similar immunologic marker patterns. The numerous markers available in the flow cytometry laboratory make these patterns difficult to remember, especially for those of uncommon neoplasms. We describe the design and implementation of a Web-based database for diagnosis of haematologic neoplasms using results of immunophenotyping by flow cytometry. This database aims to assist pathology and haematology residents in interpreting flow cytometry data, and is designed to reach a wide base of users who use a variety of browsers on different computer platforms. Five modules are developed in this comprehensive program: (a) differential diagnosis: to generate a list of differential diagnoses that closely match the marker results in a given case; (b) display of disorders: typical results of markers for each disorder; (c) display of markers: relevant information of each immunologic marker; (d) display of archived cases for a disorder: marker results of cases previously diagnosed for a disorder; and (e) display of summary for archived cases: summary of marker results of all the archived cases for each disorder. Our experience with this Web-based database in teaching pathology residents has been very encouraging. Since the World Wide Web is increasingly more accessible to computer users, it has become an ideal medium for distribution of clinical decision-support software. PMID- 11783715 TI - Cost effectiveness of a medical digital library. AB - The rapid increase in the price of electronic journals has made the optimization of collection management an urgent task. As there is currently no standard procedure for the evaluation of this problem, we applied the Reading Factor (RF), an electronically computed indicator used for consultation of individual articles. The aim of our study was to assess the cost effective impact of modifications in our digital library (i.e. change of access from the Intranet to the Internet or change in editorial policy). The digital OVID library at Rouen University Hospital continues to be cost-effective in comparison with the interlibrary loan costs. Moreover, when electronic versions are offered alongside a limited amount of interlibrary loans, a reduction in library costs was observed. PMID- 11783716 TI - Contribution of the neural cell adhesion molecule to neuronal and synaptic plasticity. AB - The neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM contribute to many aspects of the development and plasticity of the central nervous system. This includes mechanisms of cell differentiation and migration, neurite outgrowth, establishment of specific patterns of synaptic connections, synaptic plasticity and long-term potentiation. How NCAM and PSA-NCAM contribute to regulate all these different mechanisms remains essentially unknown. Adhesive properties appear to be important, but recent studies also point to possible interactions between NCAM and PSA-NCAM with intracellular signalling cascades that are essential to biological functions. Some of these mechanisms are discussed and a hypothesis is proposed based on the existence of cross-talk between these molecules and signalling pathways mediated by growth factors. PMID- 11783717 TI - Hippocampal plasticity in Alzheimer's disease. AB - During recent years, many reports have indicated that in addition to the progressive neuropathology observed in Alzheimer's disease (AD), there are also plasticity-related changes in the AD brain. It is thought that these plastic events are an attempt by the brain either to try to restore structure and function or to compensate for the damage caused by the disease. Alternatively, it is possible that these changes are a part of the disease's pathologic cascade. Here we discuss our recent findings on highly polysialylated neural cell adhesion molecule (PSA-NCAM) and neuronal-expressed calcium-binding proteins in the hippocampus and entorhinal cortex of controls and patients with AD in relation to the other findings which suggest that structural plasticity is an integral part of the disease process of AD. PMID- 11783718 TI - Extracellular signal-regulated kinase, synaptic plasticity, and memory. AB - The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), has been studied extensively in recent years for its involvement in synaptic plasticity and memory function. Activation of ERK is coupled to stimulation of cell-surface proteins via several different upstream signaling pathways, and contributes to the regulation of diverse cellular processes, ranging from cell excitability to gene expression. We herein review evidence for ERK's role in different forms of synaptic plasticity and different types of learning paradigms, drawing on examples from different systems in molluscs as well as the mammalian brain. The picture that emerges is that ERK activation in response to conditions that give rise to synaptic and behavioral modification contributes to that modification in a multitude of functionally distinct ways. The functional diversity is likely to be achieved by the operation of multiple, parallel ERK cascades that differ with respect to the subcellular compartments in which ERK exerts its effects and the temporal windows during which the effects are manifested. We conclude that our understanding of the mechanisms by which ERK contributes to synaptic plasticity and memory has much to gain by further study of the signaling events up- and downstream of ERK activation and the spatiotemporal characteristics of ERK activation in association with activity dependent synaptic modification and information processing. PMID- 11783719 TI - Directing place representation in the hippocampus. AB - Theoretical models of rodent navigation consider location information and directional heading to be essential. Indeed, the existence of location-selective 'place cells' and orientation-selective 'head direction cells' is well documented. Different models suggest different forms of interaction between information about location and heading direction. However, until recently, there were no clear empirical data that could be used to distinguish the different models in terms of the nature of the integration of location and directional heading information. Recently, Leutgeb et al. provided evidence that head direction and place signals coexist within the CA1 region of hippocampus, and that the head direction signals are likely to be generated by a subpopulation of interneurons. This finding opens up new possibilities for clarifying current models and for developing biologically plausible theories of synaptic interactions between location and head direction codes. In this paper, we first present the issue concerning the nature of the interaction between location and head direction signals, followed by a selective review of place and head direction cell research. The finding of Leutgeb et al. is then summarized, and its implications for current models are discussed. Finally, a view is presented that considers place fields to be a product not only of (external and internal) sensory input, but also of non-spatial variables such as motivation and responses. The finding of Leutgeb et al. and many earlier anatomical studies suggest that hippocampal head direction, motivation and response information may be represented by the interneuron population. Thus, these factors may have strong impact on the location codes of hippocampal pyramidal neurons. Their influence may further define the behavioral context of the current spatial environment. PMID- 11783720 TI - The function of dreaming. AB - Theories on the function of REM sleep and dreaming, with which it has a contingent relationship, remain diverse. They include facilitation of memory storage, reverse learning, anatomical and functional brain maturation, catecholamine restoration, psychoanalytical (wish fulfilment or otherwise). It is possible that one function is grafted onto another as the personality develops. Given a close relationship between REM sleep and dreaming, and given that the neonate spends 18 hours asleep per day, of which 12 hours are spent in REM sleep, it is logical to look in the neonate for a primary function of dreaming. The two constants in the dreaming process are: 1) the dreamer is always present as first person observer; 2) there is always a topographical setting. Based on the foregoing, it is proposed that a major function of REM sleep is the development and maintenance of a sense of personal identity, through creating a 'being there' environment at regular intervals during prolonged periods of absence from a waking state in topographical surrounds. The infant cannot forget who he/she is. Thus, he/she develops a clear sense of his/her own identity, or the 'I'ness of me', and a sense of his/her separateness from the topographical world. At the same time, by largely forgetting the dreams, he/she is not burdened by the need for an elaborate method of storage of the vicarious and bizarre experiences. PMID- 11783721 TI - Traditional engineering in the biological century: the biotraditional engineer. AB - The increasing importance of life science in all engineering is prompting departments in the traditional engineering disciplines to offer life science as part of their curricula. Students who take advantage of this opportunity- "biotraditional engineers"--will be well positioned for careers in their discipline and in related areas of bioengineering. The founder engineering societies, such as the Bioengineering Division of ASME, are responding to this trend by broadening their scope and working increasingly across interdisciplinary borders. PMID- 11783722 TI - Stress-modulated growth, residual stress, and vascular heterogeneity. AB - A simple phenomenological model is used to study interrelations between material properties, growth-induced residual stresses, and opening angles in arteries. The artery is assumed to be a thick-walled tube composed of an orthotropic pseudoelastic material. In addition, the normal mature vessel is assumed to have uniform circumferential wall stress, which is achieved here via a mechanical growth law. Residual stresses are computed for three configurations: the unloaded intact artery, the artery after a single transmural cut, and the inner and outer rings of the artery created by combined radial and circumferential cuts. The results show that the magnitudes of the opening angles depend strongly on the heterogeneity of the material properties of the vessel wall and that multiple radial and circumferential cuts may be needed to relieve all residual stress. In addition, comparing computed opening angles with published experimental data for the bovine carotid artery suggests that the material properties change continuously across the vessel wall and that stress, not strain, correlates well with growth in arteries. PMID- 11783723 TI - Mechanical properties and microstructure of intraluminal thrombus from abdominal aortic aneurysm. AB - Accurate estimation of the wall stress distribution in an abdominal aortic aneurysm (AAA) may prove clinically useful by predicting when a particular aneurysm will rupture. Appropriate constitutive models for both the wall and the intraluminal thrombus (ILT) found in most AAA are necessary for this task. The purpose of this work was to determine the mechanical properties of ILT within AAA and to derive a more suitable constitutive model for this material. Uniaxial tensile testing was carried out on 50 specimens, including 14 longitudinally oriented and 14 circumferentially oriented specimens from the luminal region of the ILT, and 11 longitudinally oriented and 11 circumferentially oriented specimens from the medial region. A two-parameter, large-strain, hyperelastic constitutive model was developed and used to fit the uniaxial tensile testing data for determination of the material parameters. Maximum stiffness and strength were also determined from the data for each specimen. Scanning electron microscopy (SEM) was conducted to study the regional microstructural difference. Our results indicate that the microstructure of ILT differs between the luminal, medial, and abluminal regions, with the luminal region stronger and stiffer than the medial region. In all cases, the constitutive model fit the experimental data very well (R2>0.98). No significant difference was found for either of the two material parameters between longitudinal and circumferential directions, but a significant difference in material parameters, stiffness, and strength between the laminal and medial regions was determined (p<0.01). Therefore, our results suggest that ILT is an inhomogeneous and possibly isotropic material. The two parameter, hyperelastic, isotropic, incompressible material model derived here for ILT can be easily incorporated into finite element models for simulation of wall stress distribution in AAA. PMID- 11783724 TI - Modeling passive mechanical interaction between aqueous humor and iris. AB - Certain forms of glaucoma are associated with displacement of the iris from its normal contour. We present here a mathematical model of the coupled aqueous humor iris system that accountsfor the contribution of aqueous humor flow and passive iris deformability to the iris contour. The aqueous humor is modeled as a Newtonian fluid, and the iris is modeled as a linear elastic solid. The resulting coupled equation set is solved by the finite element method with mesh motion in response to iris displacement accomplished by tracking a pseudo-solid overlying the aqueous humor. The model is used to predict the iris contour in healthy and diseased eyes. The results compare favorably with clinical observations, supporting the hypothesis that passive iris deformation can produce the iris contours observed using ultrasound biomicroscopy. PMID- 11783725 TI - Steady flow and wall compression in stenotic arteries: a three-dimensional thick wall model with fluid-wall interactions. AB - Severe stenosis may cause critical flow and wall mechanical conditions related to artery fatigue, artery compression, and plaque rupture, which leads directly to heart attack and stroke. The exact mechanism involved is not well understood. In this paper a nonlinear three-dimensional thick-wall model with fluid-wall interactions is introduced to simulate blood flow in carotid arteries with stenosis and to quantify physiological conditions under which wall compression or even collapse may occur. The mechanical properties of the tube wall were selected to match a thick-wall stenosis model made of PVA hydrogel. The experimentally measured nonlinear stress-strain relationship is implemented in the computational model using an incremental linear elasticity approach. The Navier-Stokes equations are used for the fluid model. An incremental boundary iteration method is used to handle the fluid-wall interactions. Our results indicate that severe stenosis causes considerable compressive stress in the tube wall and critical flow conditions such as negative pressure, high shear stress, and flow separation which may be related to artery compression, plaque cap rupture, platelet activation, and thrombus formation. The stress distribution has a very localized pattern and both maximum tensile stress (five times higher than normal average stress) and maximum compressive stress occur inside the stenotic section. Wall deformation, flow rates, and true severities of the stenosis under different pressure conditions are calculated and compared with experimental measurements and reasonable agreement is found. PMID- 11783726 TI - Distribution of hepatic venous blood in the total cavo pulmonary connection: an in vitro study into the effects of connection geometry. AB - The total cavo pulmonary connection, or TCPC, is a surgical correction to congenital heart defects. The geometry of this connection has been shown to determine the fluid power loss as well as the distribution of hepatic fluid that enters through the inferior vena cava. In vitro studies were performed to measure the power loss and hepatic fluid distribution in models of the TCPC with four different geometries. It was found that a zero offset straight geometry provided good hepatic fluid distribution but large power loss. A zero offset flared geometry provided low power loss but poor hepatic fluid distribution. The optimal geometry from those tested was found to be the zero offset cowl geometry whereby an enlargement was made on one side of the inferior and superior vena cava. So long as the cowl was directed toward the pulmonary artery of lowest flow rate, low power loss and relatively good distribution of hepatic flow could be obtained. PMID- 11783727 TI - A computational study of the hemodynamics after "edge-to-edge" mitral valve repair. AB - Edge-to-edge mitral valve repair consists in suturing the free edge of the leaflets to re-establish coaptation in prolapsing valves. The leaflets are frequently sutured at the middle and a double orifice valve is created. In order to study the hemodynamic implications, a parametric model of the left heart has been developed. Different valve areas and shapes have been investigated. Results show that the simplified Bernoulli formula provides a good estimation of the pressure drop and that the pressure drop may be predicted on the basis of the pre operative geometric and hemodynamics data by means of customized models. PMID- 11783728 TI - A numerical analysis of phonation using a two-dimensional flexible channel model of the vocal folds. AB - A two-dimensional flexible channel model of the vocal folds coupled with an unsteady one-dimensional flow model is presented for an analysis of the mechanism of phonation. The vocal fold is approximated by springs and dampers distributed in the main flow direction that are enveloped with an elastic cover. In order to approximate three-dimensional collision of the vocal folds using the two dimensional model, threshold values for the glottal width are introduced. The numerical results show that the collision plays an important role in speech sound, especially for higher resonant frequency components, because it causes the source sound to include high-frequency components. PMID- 11783729 TI - Liquid plug flow in straight and bifurcating tubes. AB - A finite-length liquid plug may be present in an airway due to disease, airway closure, or by direct instillation for medical therapy. Air forced by ventilation propagates the plug through the airways, where it deposits fluid onto the airway walls. The plug may encounter single or bifurcating airways, an airway surface liquid, and other liquid plugs in nearby airways. In order to understand how these flow situations influence plug transport, benchtop experiments are performed for liquid plug flow in: Case (i) straight dry tubes, Case (ii) straight pre-wetted tubes, Case (iii) bifurcating dry tubes, and Case (iv) bifurcating tubes with a liquid blockage in one daughter. Data are obtainedfor the trailing film thickness and plug splitting ratio as a function of capillary number and plug volumes. For Case (i), the finite length plug in a dry tube has similar behavior to a semi-infinite plug. For Case (ii), the trailing film thickness is dependent upon the plug capillary number (Ca) and not the precursor film thickness, although the shortening or lengthening of the liquid plug is influenced by the precursor film. For Case (iii), the plug splits evenly between the two daughters and the deposited film thickness depends on the local plug Ca, except for a small discrepancy that may be due to an entrance effect or from curvature of the tubes. For Case (iv), a plug passing from the parent to daughters will deliver more liquid to the unblocked daughter (nearly double, consistently) and then the plug will then travel at greater Ca in the unblocked daughter as the blocked. The flow asymmetry is enhanced for a larger blockage volume and diminished for a larger parent plug volume and parent-Ca. PMID- 11783730 TI - An analysis of the effect of lower extremity strength on impact severity during a backward fall. AB - At least 280 000 hip fractures occur annually in the U.S. at an estimated cost of $9 billion. While over 90 percent of these are caused by falls, only about 2 percent of all falls result in hip fracture. Evidence suggests that the most important determinants of hip fracture risk during a fall are the body's impact velocity and configuration. Accordingly, protective responses for reducing impact velocity and the likelihood for direct impact to the hip, strongly influence fracture risk. One method for reducing the body's impact velocity and kinetic energy during a fall is to absorb energy in the lower extremity muscles during descent, as occurs during sitting and squatting. In the present study, we employed a series of in verted pendulum models to determine: (a) the theoretical effect of this mechanism on impact severity during a backward fall, and (b) the effect on impact severity of age-related declines (or exercise-induced enhancements) in lower extremity strength. Compared to the case of a fall with zero energy absorption in the lower extremity joints, best-case falls (which involved 81 percent activation of ankle and hip muscles, but only 23 percent activation of knees muscles) involved 79 percent attenuation (from 352 J to 74 J) in the body's vertical kinetic energy at impact (KEv), and 48 percent attenuation (from 3.22 to 1.68 m/s) in the downward velocity of the pelvis at impact (v(v)). Among the mechanisms responsible for this were: (1) eccentric contraction of lower extremity muscles during descent, which resulted in up to 150 J of energy absorption; (2) impact with the trunk in an upright configuration, which reduced the change in potential energy associated with the fall by 100 J; and (3) knee extension during the final stage of descent, which "transferred" up to 90 J of impact energy into horizontal (as opposed to vertical) kinetic energy. Declines in joint strength reduced the effectiveness of mechanisms (1) and (3), and thereby increased impact severity However, even with reductions of 80 percent in available torques, KEv was attenuated by 50 percent. This indicates the importance of both technique and strength in reducing impact severity. These results provide motivation for attempts to reduce elderly individuals' risk for fall-related injury through the combination of instruction in safe falling techniques and exercises that enhance lower extremity strength. PMID- 11783731 TI - Three-dimensional dynamic simulation of total knee replacement motion during a step-up task. AB - A three-dimensional dynamic model of the tibiofemoral and patellofemoral articulations was developed to predict the motions of knee implants during a step up activity. Patterns of muscle activity, initial joint angles and velocities, and kinematics of the hip and tinkle were measured experimentally and used as inputs to the simulation. Prosthetic knee kinematics were determined by integration of dynamic equations of motion subject to forces generated by muscles, ligaments, and contact at both the tibiofemoral and patellofemoral articulations. The modeling of contacts between implants did not rely upon explicit constraint equations; thus, changes in the number of contact points were allowed without modification to the model formulation. The simulation reproduced experimentally measured flexion-extension angle of the knee (within one standard deviation), but translations at the tibiofemoral articulations were larger during the simulated step-up task than those reported for patients with total knee replacements. PMID- 11783732 TI - A microstructural finite element simulation of mechanically induced bone formation. AB - A finite element method to simulate the formation of an interconnected trabectular bone microstructure oriented with respect to applied in vivo mechanical forces is introduced and quantitatively compared to experimental data from a hydraulic bone chamber implant model. Randomly located 45 microm mineralized nodules were used as the initial condition for the model simulations to represent an early stage of intramembranous bone formation. Boundary conditions were applied consistent with the mechanical environment provided by the in vivo bone chamber model. A two-dimensional repair simulation algorithim that incorporated strain energy density (SED), SED gradient, principal strain, or principal strain gradient as the local objective criterion was utilized to simulate the formation of an oriented trabecular bone microstructure. The simulation solutions were convergent, unique, and relatively insensitive to the assumed initial distribution of mineralized nodules. Model predictions of trabecular bone morphology and anisotropy were quantitatively compared to experimental results. All simulations produced structures that qualitatively resembled oriented trabecular bone. However only simulations utilizing a gradient objective criterion yielded results quantitatively similar to in vivo observations. This simulation approach coupled with an experimental model that delivers controlled in vivo mechanical stimuli can be utilized to study the relationship between physical factors and microstructural adaptation during bone repair. PMID- 11783733 TI - Modeling modulus reduction in bovine trabecular bone damaged in compression. AB - Loading bone beyond its yield point creates microdamage, leading to reduction in stiffness. Previously, we related microdamage accumulation to changes in mechanical properties. Here, we develop a model that predicts stiffness loss based on the presence of microdamage. Modeling is done at three levels: (1) a single trabecula, (2) a cellular solid consisting of intact, damaged, and fractured trabeculae, and (3) a specimen with a localized damage band. Predictions of a reduced modulus agree well with experimental measured modulus reductions of post-yield compression of bovine trabecular bone. The predicted reduced modulus is relatively insensitive to changes in the input parameters. PMID- 11783734 TI - Evaluation of cement stresses in finite element analyses of cemented orthopaedic implants. AB - Stress analysis of the cement fixation of orthopaedic implants to bone is frequently carried out using finite element analysis. However the stress distribution in the cement layer is usually intricate, and it is difficult to report it in a way that facilitates comparison of implants for pre-clinical testing. To study this problem, and make recommendations for stress reporting, a finite element analysis of a hip prosthesis implanted into a synthetic composite femur is developed. Three cases are analyzed: a fully bonded implant, a debonded implant, and a debonded implant where the cement is removed distal to the stem tip. In addition to peak stresses, and contour and vector plots, a stressed volume and probability-of-failure analysis is reported. It is predicted that the peak stress is highest for the debonded stem, and that removal of the distal cement more than halves this peak stress. This would suggest that omission of the distal cement is good for polished prostheses (as practiced for the Exeter design). However, if the percentage of cement stressed above a certain threshold (say 3 MPa) is considered, then the removal of distal cement is shown to be disadvantageous because a higher volume of cement is stressed to above the threshold. Vector plots clearly demonstrate the different load transfer for bonded and debonded prostheses: A bonded stem generates maximum tensile stresses in the longitudinal direction, whereas a debonded stem generates most tensile stresses in the hoop direction, except near the tip where tensile longitudinal stresses occur due to subsidence of the stem. Removal of the cement distal to the tip allows greater subsidence but alleviates these large stresses at the tip, albeit at the expense of increased hoop stresses throughout the mantle. It is concluded that a thorough analysis of cemented implants should not report peak stress, which can be misleading, but rather stressed volume, and that vector plots should be reported if a precise analysis of the load transfer mechanism is required. PMID- 11783735 TI - Frictional insertion kinetics of bone biopsy needles. AB - Patients undergoing a percutaneous bone biopsy often complain of pain during needle insertion, despite local anesthesia. Bone biopsy needles are typically inserted with combined axial and twisting motions. These motions could cause pain through frictional heating or direct mechanical irritation. The hypothesis of this study is that the insertion energy of bone biopsy needles can be reduced by modifying the insertion kinetics or by adding a friction-lowering coating to the needles. Jamshidi bone biopsy needles were driven into a bone analog model by an MTS materials testing machine operating under axial and rotational displacement control. The load/torque recordings showed that, to significantly decrease insertion energy and peak resistance to needle insertion, axial velocity and angular frequency had to be decreased to one quarter of the baseline, typical usage parameters. However the increased insertion time may not be acceptable clinically. The majority of the insertion energy was associated with the needle axial thrust rather than with needle twisting. Overcoming friction against the side of the needle consumed much more of the insertion energy than did the process of cutting per se. None of five needle coatings tested succeeded in appreciably lowering the insertion energy, and none achieved a substantial decrease in peak resisting force. PMID- 11783736 TI - Effect of plaque composition on fibrous cap stress in carotid endarterectomy specimens. PMID- 11783737 TI - Stress, strain, and mechanotransduction in cells. AB - It is widely accepted that numerous cell types respond to mechanical stimuli, yet there is no general agreement as to whether particular cells respond directly to stress, strain, strain-rate, strain-energy, or other mechanical quantities. By recalling the definitions of the mathematical (not physical) concepts of stress and strain, it is suggested herein that cells cannot respond directly to these continuum metrics or to quantities derived from them--mechanistic models will need to be based on more fundamental quantities, as, for example, inter-atomic forces or conformational changes of the appropriate molecules. Nonetheless, the concepts of stress and strain should continue to play an important role in mechanobiology, both in the identification of empirical correlations and in the development of phenomenological constitutive models, each of which can contribute to our basic understanding as well as help in the design of future experiments and some clinical interventions. It is important to remember, therefore, that empirical correlations and most constitutive relations in continuum mechanics do not seek to model the actual physics--rather, their utility is in their predictive capability, which is often achieved via different relations in terms of different metrics for the same material under different conditions. Hence, with regard to quantifying cellular responses to mechanical stimuli, we must delineate between the identification of fundamental mechanisms and the formulation of phenomenological correlations, the latter of which only requires convenient metrics that need not be unique or physical. PMID- 11783740 TI - The social contextual approach and rural adolescent substance use: implications for prevention in rural settings. AB - Adolescents in rural areas use substances at rates comparable to urban adolescents; understanding causes of rural adolescent substance use is critical if prevention efforts are to succeed. The present review has three primary goals: (1) to define rural, (2) to evaluate the empirical evidence regarding correlates and causes of rural adolescent substance use from a social contextual framework (L. V. Scaramella, R. D. Conger, R. Spoth, & R. L. Simons, in press), and (3) to discuss the malleability of theoretically based risk or protective factors in rural settings. The review concludes with a discussion of the difficulties and challenges of implementing prevention programs in rural areas. PMID- 11783739 TI - An examination of the tripartite model of anxiety and depression and its application to youth. AB - The ability to differentiate anxiety and depression has been a topic of discussion in the adult and youth literatures for several decades. The tripartite model of anxiety and depression proposed by L. A. Clark and D. Watson (1991) has helped focus the discussion. In the tripartite model, anxiety is characterized by elevated levels of physiological hyperarousal (PH), depression is characterized by low levels of positive affect (PA), and negative affect (NA) or generalized emotional distress is common to both. The advent of the model led to the development of measures of tripartite constructs and subsequent validity studies. The tripartite model and resultant activity concerning the model was largely devoted to adult samples. However. those interested in anxiety and depression among youth are now incorporating the tripartite model in their work. This paper examines the current influence of the tripartite model in the youth literature, especially with regard to measuring anxiety and depression. PMID- 11783741 TI - A cross-cultural and developmental analysis of self-esteem in Chinese and Western children. AB - In this review, we examine the construct of self-esteem from a cross-cultural perspective in Chinese and Western children and adolescents. We also explore the role of childrearing practices in the development of self-esteem in these different cultures. In doing so, we first review the concepts of emic (i.e., variations in patterns of behavior within a given culture) and etic research (i.e., variations in common patterns of behavior or activities across cultures). Then, we invoke Berry's notions of "imposed-etic" and "derived-etic" approaches (J. Berry, 1989) in understanding crucial cross-cultural differences that are evident in the literature. We pose basic questions such as: (1) What does self esteem "look" like in Chinese children? (2) How do childrearing practices in China influence the development of self-esteem in children? And, (3) what are the limitations of cross-cultural research in understanding a phenomenon such as self esteem? We suggest that self-esteem does not "mean" the same things across these collectivist and individualistic cultures. We conclude our discourse with specific recommendations for clinical theory, research, and practice. PMID- 11783738 TI - Families of children with attention-deficit/hyperactivity disorder: review and recommendations for future research. AB - This review integrates and critically evaluates what is known about family characteristics associated with childhood Attention-Deficit/Hyperactivity Disorder (ADHD). Evidence suggests that the presence of ADHD in children is associated to varying degrees with disturbances in family and marital functioning, disrupted parent-child relationships, specific patterns of parental cognitions about child behavior and reduced parenting self-efficacy, and increased levels of parenting stress and parental psychopathology, particularly when ADHD is comorbid with conduct problems. However, the review reveals that little is known about the developmental mechanisms that underlie these associations, or the pathways through which child and family characteristics transact to exert their influences over time. In addition, the influence of factors such as gender, culture, and ADHD subtype on the association between ADHD and family factors remains largely unknown. We conclude with recommendations regarding the necessity for research that will inform a developmental psychopathology perspective of ADHD. PMID- 11783742 TI - Should abstinence be the goal for alcohol treatment? Affirmative viewpoint. PMID- 11783743 TI - Should abstinence be the goal for alcohol treatment? Negative viewpoint. PMID- 11783744 TI - Effect of opioid dependence pharmacotherapies on zidovudine disposition. AB - Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l-alpha-acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p = .75), buprenorphine (p = .37), or naltrexone (p = .34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity. PMID- 11783745 TI - Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients. AB - The goal of his study was to evaluate in 1,951 acute psychiatric inpatients the reliability, construct, convergent, and predictive validity of substance-induced psychiatric syndrome ratings made by clinical attending pschiatrists. The primary admitting condition for each subject was categorically rated by clinical attendings as not, mildly, moderately, or mostly substance-induced at both admission and discharge. Individual substance categories were associated with characteristic demographic, clinical treatment response, and length of stay, findings indicating good construct, predictive validity, and clinical utility. A linear dimensional approach to rating substance-induced syndromes in acute clinical populations may be preferable to the simple dichotomous approach used in DSM-IV. PMID- 11783746 TI - Screening for drug and alcohol abuse among older adults using a modified version of the CAGE. AB - This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over draw from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down'' item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse. PMID- 11783747 TI - Anger and depressive states among treatment-seeking drug abusers: testing the psychopharmacological specificity hypothesis. AB - The aim of this study was to examine the self-medication hypothesis (SMH) of substance abuse. The SMH suggests that drug abuse is driven by an attempt to alleviate specific psychological distress. One prediction from the SMH hypothesis is that drugs of abuse, because of their different pharmacological properties, attract specific patient subgroups. Specifically, this study tested the hypothesis' that opiate abusers experience difficulty managing aggression and that cocaine abusers suffer from distress associated mostly with depression. The State-Trait Anger Expression Inventory (STAXI) and the Beck Depression Inventory II were used to examine levels of anger and depression among three groups of substance abusers (opiates, cocaine, cannabis), defined by their primary drug of abuse. Anger and depression scores were elevated, but contrary to Khantzian's hypothesis, there were few differences between groups, and if anything, opiate addicts were more depressed and the cocaine abusers were angrier on several subscales. Data are discussed in terms of diagnosis and clinical treatment implications. PMID- 11783748 TI - Motivational interviewing to enhance treatment initiation in substance abusers: an effectiveness study. AB - Sixty individuals referred for a substance abuse evaluation by a child welfare worker were randomly assigned to either a standard evaluation or an evaluation enhanced by Motivational Interviewing techniques, each delivered in a single session. Participants who received the enhanced evaluation were significantly more likely to attend at least one additional treatment session after the initial evaluation (59% versus 29%). This finding suggests that comparatively inexpensive modifications of "standard" initial evaluations with substance-using parents may increase engagement of substance-abusing parents in treatment. Moreover, this study adds to an overwhelmingly positive literature supporting Motivational Interviewing with alcohol-using populations and extends prior findings to non research community settings. PMID- 11783749 TI - Gamma-aminobutyric acidA and benzodiazepine receptor alterations in the rat brain after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. AB - Gamma-aminobutyric acidA (GABA(A)) and benzodiazepine (BZ) receptors and dopamine uptake sites in 6-hydroxydopamine-treated rat brains were studied by receptor autoradiography using [3H]muscimol, [3H]flunitrazepam and [3H]mazindol binding, respectively. The rats were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks post-lesion. Degeneration of the nigrostriatal pathway after 6-hydroxydopamine treatment caused a significant loss of dopamine uptake sites in the ipsilateral striatum and substantia nigra (SN) in the lesioned animals. In the contralateral side, however, dopamine uptake sites showed no significant changes in the brain throughout the experiments. On the other hand, no significant changes in GABA(A) receptors were observed in the brain of both the ipsilateral and contralateral sides during post-lesion. In contrast, BZ receptors were observed significantly increased in the ventromedial part of striatum of the ipsilateral side from 2 to 4 weeks post-lesion. Furthermore, a transient increase in BZ receptors was found in the ipsilateral SN only at 2 weeks post-lesion. In contralateral side, most regions examined showed no significant changes in BZ receptors throughout the experiments except for a transient increase in the SN at 1 week post-lesion. These results demonstrate that 6-hydroxydopamine can cause severe functional damage in dopamine uptake sites in the nigrostriatal pathway. Our results also suggest that the change in BZ receptors is more pronounced than that in GABA(A) receptors in the brain after 6-hydroxydopamine treatment. Furthermore, our findings suggest that the increase in BZ receptors in the brain of 6-hydroxydopamine-treated model may be due to the additional disruption of the nigrostriatal dopamine system. Thus, investigations into possible changes in neurotransmitter receptors other than dopaminergic receptors appear to be important for the elucidation of pathogenesis of Parkinsons disease. PMID- 11783750 TI - Epidemiology of traumatic brain injuries: Indian scenario. AB - Traumatic brain injuries (TBIs) are a leading cause of morbidity, mortality, disability and socioeconomic losses in India and other developing countries. Specific topics addressed in this paper include magnitude of the problem, causes, context of injury occurrence, risk factors, severity, outcome and impact of TBIs on rapidly transforming societies. It is estimated that nearly 1.5 to 2 million persons are injured and 1 million succumb to death every year in India. Road traffic injuries are the leading cause (60%) of TBIs followed by falls (20%-25%) and violence (10%). Alcohol involvement is known to be present among 15%-20% of TBIs at the time of injury. The rehabilitation needs of brain injured persons are significantly high and increasing from year to year. India and other developing countries face the major challenges of prevention, pre-hospital care and rehabilitation in their rapidly changing environments to reduce the burden of TBIs. PMID- 11783751 TI - CNS child abuse: epidemiology and prevention. AB - The problem of child abuse and the central nervous system implications are reviewed from a multidimensional approach. Statistics regarding prevalence, risk factors, epidemiological considerations, and physiological aspects are studied. The incidence is reviewed in the United States and in other countries where incidence and social services are also described. Implications for prevention efforts are considered. PMID- 11783752 TI - Result of nationwide survey of the management of severe head injury in Japan. AB - A nationwide survey of the management of severe head injury was carried out in 1988 by sending the questionnaires to 1,088 main neurosurgical hospitals in Japan. The items of the survey included annual number of patients with closed severe head injury (GCS score of 8 or less), place of patients' care, type of neuromonitorings, medical and surgical treatments, severity and outcome measures. Out of 1,088 questionnaires, 457 (42% response rate) were collected and analyzed. Characteristic features of the management status were the scarcity of patients annually in each institution, limited use of specific neuromonitorings, and variety of the actual managements. Aggressive managements such as hyperventilation, barbiturate and/or hypothermia have been employed in many hospitals to control high ICP. External and internal decompression are also used widely for intradural hematomas. These results clarified not only present status of Japan but also the problems to be solved in the actual managements. PMID- 11783753 TI - Epidemiology, prevention and countermeasures against severe traumatic brain injury in Japan and abroad. AB - On the basis of accurate statistical reports in regard to traffic accidents and safety in Japan, it is clear that traffic accidents on the road, injured victims and all other losses due to these accidents have been increasing since around 1980. Nevertheless, the number of deaths due to traffic accidents has been gradually declining over the last six years. More detailed analysis of data revealed that the most significant factor for the recent reduction of traffic accident deaths was the marked reduction of deaths related to head injury. From the neurosurgical viewpont, the Japanese Data Bank Committee for Traumatic Brain Injury began its formal activity in 1998. Although the registered number of severe head injuries is statistically too small at present to arrive at conclusions, some interesting points draw our attention. As for intracranial pathology diagnosed by the image of cranial CT scans, two thirds of nontraffic cases have focal brain lesions alone. On the other hand, in traffic cases one third of patients have focal lesions alone and one fourth have diffuse brain lesion exclusively. In this study, in 23% of traffic accidents and 12% of nontraffic accidents, consumption of alcohol led indirectly to head injuries. The schedule and details of countermeasures taken against traffic accidents are discussed from an international viewpoint. PMID- 11783754 TI - Surgical treatment of primary supratentorial intracerebral hemorrhage in stuporous and comatose patients. AB - Primary supratentorial intracerebral hemorrhage can be considered as one of the most devastating forms of cerebrovascular disease. Reduction in intracranial volume buffering capacity and severe intracranial pressure are the most important factors related to a poor prognosis in cases with huge hematoma and altered state of consciousness. The role of surgery in the management of such cases appears still controversial. Nevertheless, it is conceivable that some cases with poor natural outcome might benefit from surgical evacuation. Fifty patients with altered state of consciousness and primary supratentorial intracerebral hemorrhage ranging from 24 to 75 ml were submitted to surgical evacuation of the hematoma. The decision to operate was based on the presence of signs indicating an oncoming severe intracranial hypertension. In 15 patients, in whom a progression in brain swelling was expected to occur after the hematoma evacuation, a decompressive craniectomy, associated with dural enlargement, was performed after the initial surgical procedure. The overall analysis of the clinical results at one year after surgery showed 40% of complete recovery and 38% of improvement. A significant statistical correlation was found between outcome and pre-operative neurological status. The association of decompressive craniectomy and dural enlargement to hematoma evacuation, proved very useful in a group of severely compromised patients. Surgical treatment of patients with primary supratentorial intracerebral hemorrhage and altered state of consciousness can have a positive role, in selected cases, by minimizing the life threatening progression of intracranial hypertension. PMID- 11783755 TI - Surgical management of cavernous malformations of the brainstem. AB - Cavernomas are well circumscribed lesions formed by sinusoidal vascular channels. They tend to slowly expand in size and carry a 0.7% to 1.1% annual risk of hemorrhage. Only 10% to 30% of intracranial cavernomas are located in the posterior fossa. When located in the brainstem they can cause recurrent hemorrhages and devastating neurological deficits. The authors report a series of cavernomas located in the brainstem and present a review on their epidemiology, pathogenesis, natural history, and methods of diagnosis and treatment. Although the surgical treatment of brainstem cavernomas can be associated with a significant risk, surgical resection is recommended of the lesions that have hemorrhaged or grown producing progressive deficits. The authors' experience on the surgical treatment of cavernous hemangiomas of the brainstem, indicating important aspects of intra-operative surgical techniques, is presented, including a clinical and anatomical correlation of different surgical approaches to brainstem cavernomas. PMID- 11783756 TI - Brain injury: analysis of imaging modalities. AB - Advances in imaging have had a significant impact not only on the diagnosis of but also on the management of patients with brain injury. Various modalities are available to image the brain; however, it is not always clear which imaging modality (CT, MRI, SPECT, PET, etc.) is optimal for a specific aspect of traumatized brain. The purpose of this paper is to analyze the over 20,000 imaging studies done in brain injury and to compare the results with the experience in the literature. A detailed comparison has been done relative to CT, MRI, SPECT and PET in traumatic brain injury. PMID- 11783757 TI - Ischemic stroke in elderly patients treated with a free radical scavenger glycolytic intermediate solution: a preliminary pilot trial. AB - The safety and tolerability of a free radical scavenger with Na+ channel blocking activity (dimethyl sulfoxide (DMSO)) combined with a glycolytic intermediate and high energy substrate (fructose 1,6-disphosphate (FDP)) were assessed in a mostly elderly patient group presenting with acute and subacute ischemic stroke. Eleven patients (average age 65) were given i.v. infusions of DMSO-FDP twice daily for an average of 12 days, while five control patients (average age 63) were given standard therapy. Safety and tolerability were evaluated by clinical adverse effects to drug therapy. Efficacy of DMSO-FDP was assessed by MRI lesion size, by magnetic resonance angiography of ischemic territory, and by a 5-point neurologic recovery scale that rated sensory-motor function and level of consciousness. Results suggest that DMSO-FDP administration is safe, well-tolerated and may be of benefit when given within 12 h after the onset of stroke symptoms. No significant changes in blood pressure, EKG, heart rate or hematology and chemistry profiles, were recorded in any patient receiving DMSO-FDP. Neurologic evaluation at 1, 3 and 6 months after treatments revealed that 7 of 11 (63%) patients given DMSO-FDP achieved 'improved' or 'markedly improved' status while 1 of 5 (20%) standard treated patients showed 'improved' status and only at the 3 month follow-up. This preliminary trial indicates that DMSO-FDP is well tolerated by this group of elderly patients and could be of benefit in reducing neurologic disability after stroke. PMID- 11783758 TI - Astrocytes mediate cerebral cortical neuronal axon and dendrite growth, in part, by release of fibroblast growth factor. AB - Astrocytes occupy a central role in central nervous system (CNS) function. In particular astyrocytes can support neurite growth, in part, by release of diffusable factors. We therefore performed biochemical analysis of astrocyte conditioned medium to examine possible mechanisms of astrocyte mediated axon and dendrite growth in the mammalian CNS. Culture medium was conditioned on purified astrocyte monolayers derived from P3 rat cerebral cortex or on fibroblasts. Conditioned medium (CM) was subject to protein denaturation, molecular weight fractionation, and heparin affinity chromatography. E18 mouse cerebral cortical neurons were then cultured in the various media or directly on astrocyte monolayers and axon and dendrite growth from 50 neurons in each condition quantified after 3 DIV using double-labeled immunohistochemical techniques. Axon and dendrite growth was supported by astrocyte CM and both were significantly greater than process growth from neurons incubated in fibroblast CM. Protein denaturation significantly reduced astrocyte CM support of axon and dendrite growth. Following ultrafiltration and dialysis dendrite and axon growth was observed in the molecular weight fraction between 10 and 100 kDa. Axon growth also was observed in the CM molecular weight fraction greater than 100 kDa. Conditioned medium was eluted on a heparin column; when the bound fragment was reconstituted in chemically defined medium extensive dendrite and axon growth was observed. Since fibroblast growth factor (FGF) has these biochemical characteristics we added anti-bFGF neutralizing antibodies to astrocyte monolayers or CM; this significantly reduced astrocyte support of process growth. By contrast, the addition of heparin, which helps activate FGF receptors, to astrocyte CM further enhanced process growth. Western blot analysis confirmed that bFGF was present in astrocyte CM. We then examined axon and dendrite growth from cortical neurons after the addition of various growth factors to chemically defined medium. Axon and dendrite growth, similar to that found in astrocyte CM was observed after the addition of bFGF or aFGF. Astrocyte support of cerebral cortical neuron axon and dendrite growth in vitro may be explained, in part, by FGF release. PMID- 11783759 TI - Main subunits of ionotropic glutamate receptors are expressed in isolated rat brain microvessels. AB - Excitatory amino acids are known to modulate blood-brain barrier (BBB) permeability, however, the information on glutamate receptors in cerebral capillaries is inconsistent. In the present study, freshly isolated microvessels obtained from saline-perfused rat brains were used. Gene expression of the main N methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole-4 propionic acid (AMPA) receptor subunits NMDAR1 and GLUR1, respectively, were investigated by reverse transcription-polymerase chain reaction (RT-PCR). The results confirmed the presence of both NMDAR1 and GLUR1 mRNAs in microvessels of seven brain regions studied. Moreover, specific binding of [3H]glutamate to capillary membranes and its displacement by AMPA, NMDA and metabotropic, but not kainate receptor agonists were observed. These results suggest that rat brain capillaries and/or albuminally adhering astrocyte processes possess functional glutamate receptors. Thus, the effects of glutamate agonists and antagonists in modulation of BBB function might be mediated directly by cerebral microvessels. PMID- 11783761 TI - Compassion and mercy in the practice of medicine. PMID- 11783760 TI - A model of global forebrain ischemia/reperfusion in the awake rat. AB - Anesthesia is an essential element during the induction of ischemia/reperfusion and cerebral blood flow (CBF) measurement in most animal models. Cerebral neuroprotection and intrinsic effects on CBF afforded by anesthetics are confounding variables in those models. A new model of global forebrain ischemia/reperfusion (GFIR) in awake rats is presented and characterized. Rats underwent permanent occlusion of the basilar, and the paired pterygopalatine, external carotid, and occipital arteries. Inflatable balloon occluders were inserted around both common carotids, the nine-vessel occlusion (9VO) preparation. A subgroup of 9VO rats underwent placement of a laser Doppler flowmetry (LDF) probe for measurement of cortical CBF. Twenty-four hours later, while awake, 9VO rats were subjected to 10 min of ischemia by occluding both common carotid arteries. Blood gases, glucose and hematocrit were analyzed before and during ischemia, and for up to 90 min during reperfusion. Behavioral observations and continuous LDF CBF and mean arterial blood pressure determinations during ischemia and reperfusion were made. Rats were rendered comatose and decerebrate rigidity was observed during 9VO. Following balloon deflation, rats immediately regained the righting reflex and achieved complete recovery in the next 24 h. Moderate hyperglycemia was observed at 5 min of ischemia and up to 90 min reperfusion in 9VO rats. LDF CBF decreased to 5% of baseline and remained unchanged during ischemia. The 9VO is a reproducible recovery model of GFIR. Behavioral and LDF CBF correlates are consistent and survival studies are feasible. PMID- 11783762 TI - Acidosis correction with a new 25 mmol/l bicarbonate/15 mmol/l lactate peritoneal dialysis solution. AB - OBJECTIVE: The aim of this study was to evaluate the effects of a combined 25 mmol/L bicarbonate/15 mmol/L lactate-based solution (Bic/Lac), compared to a 35 mmol/L lactate solution (Lac)--the most commonly used solution for patients in southern Europe--on the venous plasma bicarbonate level in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This was a randomized, parallel, controlled, open-label study, with patients studied for a period of 3 months preceded by a 1-month baseline and followed by a 1-month follow-up. Patients used the 35 mmol/L lactate solution during baseline and follow-up periods. SETTING: Four Spanish nephrology centers. PATIENTS: Thirty-one (20 Bic/Lac, 11 Lac) well-dialyzed (creatinine clearance > 55 L/week/1.73 m2 body surface area) CAPD patients. INTERVENTIONS: Blood samples were taken for biochemistry tests at all visits. A physical examination was completed at baseline and month 3, and a medical update was completed after 1, 2, and 3 months, and at the follow-up visit. Adverse-event monitoring and notation of prescription changes were carried out continuously. MAIN OUTCOME MEASURE: Effect on venous plasma bicarbonate level. RESULTS: Venous plasma bicarbonate rose by 3.1 mmol/L (confidence intervals 1.6-4.8),from a baseline level of 23.0 mmol/L during the treatment period in those patients treated with Bic/Lac (p < 0.05 vs Lac). The number of acidotic patients (venous plasma bicarbonate < 24 mmol/L) was statistically significantly reduced at every treatment period visit in the Bic/Lac group (p < 0.05). There were no adverse findings with respect to vital signs, physical examination, or clinical symptoms, apart from one death in the control group. CONCLUSIONS: The new Bic/Lac solution allowed better correction of acid-base status than the lactate solution. PMID- 11783763 TI - Emergence of mupirocin-resistant Staphylococcus aureus in chronic peritoneal dialysis patients using mupirocin prophylaxis to prevent exit-site infection. AB - OBJECTIVE: To determine the prevalence of the carriage of Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and mupirocin-resistant Staphylococcus aureus (MuRSA) in chronic peritoneal dialysis (CPD) patients after 4 years of prophylactic mupirocin application to the exit site, in a peritoneal dialysis unit. METHODS: Three swabs were collected from the nares, axillae/groin, and exit site, respectively, from 149 patients on CPD between May and July 2001. All swabs were cultured on solid selective agar (mannitol salt agar) and in mannitol salt broth. Staphylococcus aureus isolates were tested for methicillin resistance using oxacillin screening plates, and mupirocin resistance using E test strips. Low-level MuRSA was defined as minimum inhibitory concentration (MIC) of 4 mg/mL or more, and high-level MuRSA as MIC of 256 mg/mL or more. RESULTS: Staphylococcus aureus was isolated from 26 (17%) patients (25 from nares/axilla/groin, and 1 from the exit site). High-level MuRSA was isolated from 4 patients (3% of the total study population; 15% of total SA isolates). No MRSA was detected. One patient with high-level MuRSA had peritonitis due to SA, resulting in treatment failure and catheter loss, soon after the swabs were collected for the study. CONCLUSION: We report the emergence of high-level MuRSA in CPD patients after a 4-year practice of continuous use of mupirocin in a small number of patients in our unit. Our results may have significant implications for the future practice of prophylactic use of mupirocin by CPD patients to prevent exit-site infection. PMID- 11783764 TI - Dialysate cancer antigen 125 concentration as marker of peritoneal membrane status in patients treated with chronic peritoneal dialysis. AB - OBJECTIVE: This study reviews publications on the history of cancer antigen 125 (CA125), the background of its use as a marker of mesothelial cell mass, determination in peritoneal effluent, and its practical use in both the follow-up of peritoneal dialysis (PD) patients and as a marker of in vivo biocompatibility of dialysis solutions. DESIGN: Review article. RESULTS: CA125 is a high molecular weight glycoprotein. Previous studies in ascites suggested its release by mesothelial cells. In vitro studies with cultured mesothelial cells showed constitutive production, the majority of which was dependent on mesothelial cell mass. Serum CA125 is normal in PD patients, but its concentration in peritoneal dialysate suggests local release, probably from mesothelial cells. Effluent CA125 can be considered a marker of mesothelial cell mass in stable PD patients, but large amounts are found during peritonitis, due probably to necrosis of mesothelial cells. The majority of studies found no relationship between dialysate CA125 and peritoneal transport parameters. Some cross-sectional studies reported a relationship with duration of PD, but others were unable to confirm this, due probably to the large interindividual variability. Longitudinal follow up has shown a decrease in dialysate CA125, indicating loss of mesothelial cell mass. Application of theoretically more-biocompatible PD solutions causes an increase in dialysate CA125. CONCLUSIONS: Dialysate CA125 is a mesothelial cell mass marker. The concentration of CA125 should be determined after a standardized dwell. A single low value is not informative. A decrease with time on PD suggests loss of mesothelial cell mass. Dialysate CA125 is a marker of in vivo biocompatibility of (new) dialysis solutions. More research is necessary on the best methodology for measuring low concentrations and establishing normal values and a significant change. PMID- 11783765 TI - The choice of dialysis solutions in pediatric chronic peritoneal dialysis: guidelines by an ad hoc European committee. AB - OBJECTIVE: To provide guidelines on choosing dialysis solutions for children on chronic peritoneal dialysis (PD). SETTING: European Paediatric Peritoneal Dialysis Working Group. DATA SOURCE: Literature on the application of PD solutions in children (Evidence), and discussions within the group (Opinion). CONCLUSIONS: Glucose is the standard osmotic agent for PD in children (Evidence). The lowest glucose concentration needed should be used (Opinion). Low calcium solution (1.25 mmol/L) should be applied, wherever possible, with careful monitoring of parathyroid hormone levels (Opinion). The use of amino acid containing dialysis fluids can be considered in malnourished children, although aggressive enteral nutrition is preferred (Opinion). There is insufficient evidence documenting the efficacy of intraperitoneally administered amino acids (Evidence). When ultrafiltration and/or solute removal are insufficient, polyglucose solutions are a welcome addition to the treatment of children on nocturnal intermittent PD (Evidence). However, in the absence of any reported long-term experience with children, their use must be closely monitored (Opinion). Bicarbonate would appear to be the preferred buffer for PD in children, but more in vivo studies are required before it replaces the present lactate-containing solutions (Evidence/Opinion). PMID- 11783766 TI - Effects of two simplified methods of dialysate sampling on estimations of adequacy indices in automated peritoneal dialysis. AB - OBJECTIVE: To assess the effects of two simplified methods of dialysate sampling on the estimation of adequacy markers in automated peritoneal dialysis (APD). DESIGN: Cross-sectional noninterventional study. SETTING: Tertiary-care hospital. PATIENTS: Forty-nine patients undergoing standard APD therapy (36 nontidal, 13 tidal with low reserve volume). INTERVENTION: We estimated creatinine clearance (CCr), Kt/V urea, sodium removal, and peritoneal protein loss using two simplified methods. We calculated separate diurnal and nocturnal adequacies. Nocturnal concentrations of urea, creatinine, sodium, and proteins were extrapolated from dialysate samples taken after the first (method A) or the last (method B) cycle of the night. For the reference method, we estimated adequacy from a complete 24-hour dialysate collection. RESULTS: Spearman correlations versus the reference method were, for CCr, 0.82 for method A and 0.87 for method B; and for Kt/V, 0.78 (A) and 0.72 (B). Method A overestimated CCr by 19.6% (4.5 L/week)(median values) and Kt/V by 8.8% (0.12). Method B overestimated CCr by 5.0% (1.7 L/week) and Kt/V by 4.4% (0.06). Both methods estimated sodium removal accurately, but estimated protein loss poorly. Tidal APD was associated with a clear overestimation of adequacy indices with both methods. In fact, when only nontidal patients were considered, method B slightly underestimated CCr and Kt/V. CONCLUSIONS: In APD, estimation of nocturnal adequacy from dialysate samples taken after the first cycle is inaccurate. Estimation from samples taken after the last cycle yields suboptimal but acceptable results; the deviation is small and the dose of dialysis delivered to the patients is not overestimated. PMID- 11783767 TI - Recovery of renal function in Black South African patients with malignant hypertension: superiority of continuous ambulatory peritoneal dialysis over hemodialysis. AB - OBJECTIVE: To describe recovery of renal function (RC) in Black South African patients with primary malignant hypertension (MHT) and end-stage renal failure, according to the type of dialysis provided. DESIGN: A retrospective analysis of the records of 31 patients with MHT. SETTING: A university-based, large tertiary care hospital and its community-based satellite continuous ambulatory peritoneal dialysis (CAPD) clinics. PATIENTS: Only patients with renal failure caused by MHT and who were on dialysis between January 1997 and June 2000. There were 11 patients on peritoneal dialysis (PD) that regained renal function; 11 patients on hemodialysis (HD), none of whom recovered renal function; and 9 patients on PD who did not recover renal function during the same time period. OUTCOME MEASURES: The groups were investigated for variables that might predict RC. RESULTS: Peritoneal dialysis compared with HD was highly significant as an indicator of RC (p < 0.0001), with 60% of patients on PD regaining renal function, versus 0% on HD. Median time to recovery was 300 (150 -365) days. There was no significant difference in decline of mean arterial pressure (MAP) between the groups; MAP declined significantly in all groups (p = 0.00002). All groups received similar drug therapy. In the RC group, initial MAP, kidney size, and urine output tended to be higher and creatinine lower (p = not significant). Dialysis adequacy was similar in the different groups. CONCLUSIONS: This retrospective study suggests there may be benefit from PD as the primary form of dialysis when patients have MHT as a cause of their renal failure. Possible predictors of RC include blood pressure control, initial MAP, initial serum creatinine, initial urine output, and kidney size. Time should be allowed for RC before transplantation is undertaken. Prospective studies are needed to confirm the benefit of CAPD in patients with MHT. PMID- 11783768 TI - Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients. AB - OBJECTIVE: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate cefazolin and gentamicin in Thai continuous ambulatory peritoneal dialysis (CAPD) patients treated following the International Society for Peritoneal Dialysis (ISPD) 1996 recommendations for the empiric therapy of CAPD-related peritonitis. DESIGN: Prospective and descriptive study. SETTING: Institutional level of clinical care. PATIENTS: CAPD related peritonitis patients were diagnosed by dialysate effluent white cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 18 patients, all at least 15 years of age, entered; all completed the study. INTERVENTION: In accordance with the ISPD 1996 recommendations, the antibiotic regimen included continuous intraperitoneal (IP) cefazolin and once daily IP aminoglycoside. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate, respectively. Gentamicin, 0.6 mg/kg body weight, was given IP once daily. Duration of treatment was 120 hours. MAIN OUTCOME MEASURES: Serum and dialysate effluent samples of the 18 CAPD patients with peritonitis were measured and used for the synthesis of pharmacokinetic equations that could predict drug concentrations at any treatment time. RESULTS: Following administration according to the ISPD 1996 treatment recommendations, serum cefazolin reached levels higher than the recommended levels (8 microg/mL) at 3.3 minutes after drug administration, and persisted through the 5-day duration of the study. Dialysate cefazolin levels during the studied period also were persistently higher than the recommended values. The peak serum gentamicin levels were lower than the suggested values of 4 microg/mL, whereas the trough serum gentamicin levels were higher than the minimal toxic concentrations (2 microg/mL). Dialysate gentamicin levels were higher than therapeutic concentrations for only 4.75 hours in each day. It was difficult, using pharmacokinetic studies, to adjust the dosage regimen of gentamicin to achieve appropriately therapeutic levels in both serum and dialysate. CONCLUSIONS: The ISPD 1996 recommended dosage of continuous IP cefazolin could be appropriate for the treatment of CAPD-related peritonitis. Once-daily IP gentamicin administration, however, has less therapeutic benefit and should be re evaluated. PMID- 11783769 TI - Changes in employment status in end-stage renal disease patients during their first year of dialysis. AB - OBJECTIVE: To assess employment status in new end-stage renal disease (ESRD) patients at the start of dialysis and after 1 year, and to determine whether demographic and clinical variables and physical and psychosocial functioning at the start of dialysis are risk factors for loss of employment after 1 year of dialysis. DESIGN: Prospective follow-up study in which 38 of 48 Dutch dialysis centers participate. PATIENTS: 659 patients who had started on dialysis and who were between 18 and 65 years old were included. Patients were re-examined after 12 months. MAIN OUTCOME MEASURES: Demographic data, physical and psychosocial functioning with the Short-Form Health Survey (SF-36), and data on employment status were obtained using questionnaires. Nephrologists provided the clinical data. RESULTS: At the start of dialysis, 35% of patients were employed, in contrast to 61% of the general Dutch population. Within 1 year, the proportion of employed patients decreased from 31% to 25% of hemodialysis patients, and from 48% to 40% of peritoneal dialysis patients. In patients who were working at the start of dialysis, independent risk factors for loss of work within 1 year were impaired physical and psychosocial functioning [odds ratio physical: 3.4, 95% confidence interval (% CI), 1.0-11.2; odds ratio psychosocial: 4.2, 95% CI, 1.2 14.2]. CONCLUSIONS: As the percentage of employed patients at the start of dialysis is about half the expected percentage, loss of work is an important issue in both predialysis and dialysis patients. Improvements in physical and psychosocial functioning are potentially preventive of loss of work in patients who are employed when they start dialysis. PMID- 11783770 TI - Patient and technique survival on CAPD in Turkey. AB - OBJECTIVE: To analyze the status of continuous ambulatory peritoneal dialysis (CAPD) in 12 centers in Turkey. DESIGN: Retrospective study of CAPD technique and patient outcome. SETTING: University hospital renal units. PATIENTS: 334 patients [205 males (61%),129 (39%) females; mean age 42.2 +/- 13.8 years; mean follow-up time 23.5 +/- 18.3 months] beginning CAPD between March 1992 and December 1999, and having a minimum follow-up of 3 months. OUTCOME MEASURE: Patient survival, technique survival, and duration of hospitalization. RESULTS: Mean weekly Kt/V urea was 1.9 +/- 0.8, weekly creatinine clearance was 62.9 +/- 8.5 L/1.73 m2, and mean serum albumin level was 3.7 +/- 0.6 g/dL. 93 patients (28%) were withdrawn from peritoneal dialysis due to death (12.6%), transplantation (3.9%), transfer to hemodialysis (8.7%), patient failure to adapt (1.5%), and other reasons (1.2%). The major causes of death were cardiovascular disease (60%), infection (19%), malignancy (2%), and others (19%). Cox proportional hazard model analysis indicated age, serum albumin levels, comorbidity, and functional status affected survival and hospitalization (p < 0.05), whereas gender and Kt/V did not (p > 0.05). Estimation of patient survival by Kaplan-Meier analysis showed 94.2%, 88.6%, 84.5%, and 68.9% at 1, 2, 3, and 5 years respectively. Technique survival estimate by Kaplan-Meier analysis was 96.6%, 91.1%, 90.4%, and 77.4% at 1, 2, 3, and 5 years respectively. CONCLUSION: Peritoneal dialysis is an acceptable method of renal replacement therapy in Turkey. There is controversy regarding the usefulness of Kt/V in predicting mortality and morbidity. PMID- 11783771 TI - Glucose degradation products in peritoneal dialysis fluids may have both local and systemic effects: a study of residual fluid and mesothelial cells. AB - OBJECTIVE: When peritoneal dialysis (PD) fluids are heat sterilized, glucose is degraded to carbonyl compounds. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end products. However, little is known about what actually happens with glucose degradation products (GDPs) after infusion into the peritoneal cavity. The aim of the present study was to investigate possible targets for GDPs in the peritoneal cavity. DESIGN: In vitro reactions between residual fluid and GDPs were studied by incubating unused PD fluid with overnight dialysate. Confluent monolayer cultures of human mesothelial cells were used as a model to study the reactions of GDPs with the cells lining the peritoneal cavity. METHODS: Samples were analyzed, using high pressure liquid chromatography, for the presence of formaldehyde, acetaldehyde, 5-hydroxymethyl-2-furaldehyde (5-HMF), methylglyoxal, and 3-deoxyglucosone (3-DG). Cytotoxicity was determined as inhibition of proliferation of cultured fibroblasts. RESULTS: None of the analyzed GDPs reacted with overnight dialysate. Formaldehyde and methylglyoxal, in contrast to 3-DG and 5-HMF, reacted with the cultured mesothelial cells. CONCLUSIONS: Low molecular weight carbonyls such as formaldehyde and methylglyoxal most probably react with the mesothelial cells lining the peritoneal cavity, and could be responsible for the disappearance of these cells during long-term treatment. 3-Deoxyglucosone showed remarkably low reactivity and was most probably transported within the patient. PMID- 11783772 TI - Effect of nandrolone decanoate on the lipid profile of male peritoneal dialysis patients. PMID- 11783773 TI - Acyclovir-valaciclovir equilibrium between peritoneal fluid and plasma. PMID- 11783775 TI - Correction of migrated peritoneal dialysis catheters using lunderquist guidewire: a preliminary report. PMID- 11783774 TI - Success of prolonged hibernation of subcutaneously-placed peritoneal dialysis catheters. PMID- 11783776 TI - The icodextrin black line sign. PMID- 11783777 TI - Validation of a scoring system for exit-site evaluation. PMID- 11783778 TI - Serum amino acids in dialysis patients: the tryptophan/serotonin disorder hypothesis and implications for uremic anorexia. PMID- 11783779 TI - Peritoneal dialysis in patients with refractory ascites. PMID- 11783780 TI - Successful treatment of CAPD peritonitis caused by rhodotorula mucilaginosa. PMID- 11783781 TI - Direct white cell count in peritoneal effluent. A simple technique to diagnose and monitor peritonitis. PMID- 11783782 TI - Literature: November-December 2001. PMID- 11783783 TI - 2,4-Toluene diamines--their carcinogenicity, biodegradation, analytical techniques and an approach towards development of biosensors. AB - 2,4-Toluene diamine (TDA), a class A carcinogen, is a major raw material for the production of toluene diisocyanate (TDI), which is one of the precursors for the production of polyurethane foams (PU). This review deals with 2,4-toluene diamine's (TDA) carcinogenicity, analytical techniques, biodegradation and use as a biosensor for biogenic and synthetic amines, emphasizing various carcinogenicity studies by 2,4-TDA on animals and humans. This review reports some publications of the analysis of body fluid samples of workers from a PU producing factory for presence of TDA and TDI, since TDI gets absorbed into the worker's body, getting metabolized into TDA. Biodegradations of 2,4-TDA by various researchers are reported and also our own research experience with biodegradation of 2,4-TDA using Aspergillus nidulans isolated from soil site at a polyurethane foam dumping site have been discussed in this review. Biosensors for various biogenic and synthetic amines are discussed. PMID- 11783785 TI - Stepwise determination of quaternary ammonium salts and aromatic amines in pharmaceuticals by ion association titration. AB - A stepwise titrimetric method has been developed for the simultaneous determination of pharmaceutical quaternary ammonium salts (R4N+) and aromatic amines (R3N). The method is based on the solvent extraction of R4N+ and R3NH+ with an ion association reagent. Sodium tetrakis(4-fluorophenyl)borate and sodium tetraphenylborate were used as titrants and potassium tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. The ion associate which formed between R4N+ ion and TBPE made a blue color in 1,2-dichloroethane, while the ion associate formed between R3NH+ and TBPE showed a red-violet one. Sample solutions containing quaternary ammonium and/or amine compounds were titrated with sodium tetrakis(4-fluorophenyl)borate or sodium tetraphenylborate. When one drop of excess titrant was added, the color of the organic phase turned from blue or red violet to yellow at the equivalence point. On the other hand, in the mixture of R4N+ and R3N, the color changed from blue to red-violet at the first equivalence point, and then its color turned to yellow at the second equivalence point. The quaternary ammonium compound and aromatic amine in pharmaceuticals could be simultaneously and successfully determined by the proposed titration method. PMID- 11783784 TI - Determination of nucleic acids using calcein-neodymium complex as a fluorescence probe. AB - A novel fluorometric method has been developed for rapid determination of DNA and RNA with calcein-neodymium complex as a fluorescence probe. The method is based on the fluorescence enhancement of calcein-Nd(III) complex in the presence of DNA or RNA, with maximum excitation and emission wavelength at 489 nm and 514 nm, respectively. Under optimal conditions, the calibration graphs are linear over the range 0.5 - 3.0 microg/ml for both DNA and yeast RNA, 0.4 - 2.0 microg/ml for fish sperm DNA (FS DNA) and 0 - 3.0 microg/ml for calf thymus DNA (CT DNA). The corresponding detection limits are 15.1 ng/ml for DNA, 21.2 ng/ml for yeast RNA, 10.5 ng/ml for FS DNA and 8.9 ng/ml for CT DNA. The interaction mechanism for the binding of calcein-Nd(III) complex to DNA is also studied. The results of absorption spectra, fluorescence polarization measurements and thermal denaturation experiments, suggested that the interaction between calcein-Nd(III) complex and DNA is an electrostatic interaction. PMID- 11783786 TI - A handy detection cell for end-column electrochemical detection in capillary electrophoresis. AB - A handy and simple detection cell was constructed using a mixing joint for end column electrochemical detection in capillary electrophoresis (CE). The cell allows for positioning of the working electrode at the end of the separation capillary without the aid of micropositioners. The design facilitates the exchange of electrodes and capillaries without the need to refabricate the entire capillary-electrode setup. The cell can be assembled in a short period of time. Alignment with the joint screw proved to be reproducible for working electrodes of copper and gold. The advantages of reduced time and low cost make the device very attractive for the routine analysis of electroactive species, such as carbohydrates and their derivatives, purine bases and nucleosides, amino acids, and catecholamines etc. by CE with electrochemical detection. PMID- 11783787 TI - A non-potentiometric sensing method for the determination of pentoxyverine with PQC sensors based on ion-pair complexes. AB - The construction and general performance characteristics of three piezoelectric quartz crystal sensors responsive to the pentoxyverine are described here. This kind of non-potentiometric sensing method is based on use of ion-pair complexes of the pentoxyverine cation with three counter anions, namely, tungstophosphate, tetraphenylborate and picrolonate. The complexes were embedded in a PVC matrix. Adsorption of the pentoxyverine ion on the complex caused a frequency decrease of the crystal. The frequency decrease was proportional to the amount of adsorbed analyte. The influencing factors were investigated in detail, and then optimized. The proposed sensors exhibit reasonable selectivity and a higher sensitivity than the potentiometric sensors. For a sensor modified with pentoxyverine phosphotungstate, the calibration graph was linear over concentration of 1.0 x 10(-7) - 5.0 x 10(-5) M with a detection limit of 6 x 10(-8) M at pH 5.4. PMID- 11783788 TI - Comparison of different digestion methods for total decomposition of siliceous and organic environmental samples. AB - A comparison was made of different digestion methods for the total decomposition of siliceous and organically environmental samples prior to their analysis by inductively coupled plasma optical emission spectrometry (ICP-OES). In the present study, three different digestion methods, including microwave-assisted, hot plate heating and pressurized digestion (pressure bomb), were employed for the determination of nine heavy metals, i.e. Ag, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn in sediment, soil, sludge and oil. The investigation of different combinations of acids through their analytical performance demonstrated that HCl plays a vital role in the determination of silver. The combination of HNO3 and HCl possesses more reactive ability in oxidizing organic matter. The recoveries of all elements of interest in sediment (NIST 2704) obtained by different digestion methods were found to be 86% to 113%, while microwave assisted digestion with various combinations of HNO3-HCl-HF and HNO3-HClO4-HF was considered to be a viable alternative to the conventional digestion systems because of its more intensive reaction conditions. The analytical results of four certified reference materials with different matrices, including sediment (GBW 07305), soil (GBW 07411), sludge (BCR R-143) and oil (NIST 1085a), by the microwave-assisted acid digestion method indicated that the recoveries of all elements of interest were more than 85% and the throughput of applied analytical method could be elevated significantly. PMID- 11783789 TI - A unified ion chromatographic system for the determination of acidity and alkalinity. AB - A unified ion chromatographic (IC) system was developed for the determination of acidity or alkalinity. Separation column used was a reversed-phase ODS packed column, which had been modified by saturating it with lithium dodecylsulfate. A slightly acidified LiCl (50 mM LiCl and 0.05 mM H2SO4) aqueous solution was used as the eluent. By conditioning the separation column in this way, both H+ and Li+ ions became bound to the stationary phase. Dodecylsulfate groups with Li+ counterions acted as cation-exchange sites for the separation of hydrogen ions (free acidity determination). The remaining dodecylsulfate groups, with H+ counterions acted as a titrant, which reacted with basic species (total alkalinity determination). The acidity or alkalinity of each sample was measured according to the change in conductance from the eluent baseline level. A positive peak was observed from those samples with a free acidity greater than their total alkalinity, due to the separation/elution of free H+ ions. A negative peak was observed from those samples with a free acidity less than their total alkalinity. This was due to an equivalent amount of eluent H+ ions being re-supplied to the stationary phase while the "solid titrant" consumed by the acid-base reaction was regenerated. The retention time for the peak corresponding to the acidity or alkalinity was governed by the retention time for H+ ions in this IC system. Samples with a free acidity greater than 2.25 microM (tested by determination of H+ ions in pure water in equilibrium with atmospheric CO2) could be analyzed by this method. A very similar detection level was obtained for alkalinity (tested by analyzing standard aqueous NaHCO3 solutions). Aqueous solutions of some strong acid/strong-base inorganic salts were found to be slightly alkaline. This was measured as a percentage, relative to an NaHCO3 solution at the same concentration. Solutions of NaClO4, Na2SO4, NaI, NaNO3, and NaCl, gave comparative alkalinity values of 8.75%, 1.83%, 0.42%, 0.35%, and 0.33%, respectively. PMID- 11783790 TI - Liquid ionization mass spectrometry of some triorganotin carboxylates. AB - and ESI, in which [M + H]+ were not observed or the spectra were complicated. The liquid ionization mass spectra of triorganotin carboxylates varied with solvents and sample concentrations. For instance, the fragment ions [M + (C4H9)3Sn]+ of dimeric ions were observed with chloroform used as a solvent, while the [M + H]+ were observed as the base peak using ethylene dichloride. Spectra useful for the differentiation of isomers [CgH7O3Sn(C4Hg)3] were obtained by the formation of characteristic adduct ions, such as [M + EA + H]+ and [M + 2EA + H]+, with a reagent like 2-aminoethanol. Collision-induced dissociation (CID) spectra observed by ESI and LPI mass spectrometry were similar and provided less information than adduct ions did. PMID- 11783791 TI - Effects of electrolytes on the configuration change of cobalt(II)-halide complexes in chloroform/water reverse micelle systems. AB - The effects of various salts and HClO4 on the configuration change of cobalt(II) halide complexes in CHCl3/CTAC or CTAB/H2O reverse micelle systems were examined at 25 degrees C by means of spectrophotometry, where CTAC and CTAB represent cetyltrimethylammonium chloride and bromide, respectively. The formation of the [CoCl4]> or [CoBr4]2- species of the tetrahedral configuration from [Co(H2O)6]2+ of the octahedral configuration in the reverse micelles was greatly promoted not only by a decrease in the W value (W = [H2O]/[surfactant]), but also, at a constant W value (e.g., W = 2.0), by the addition of relatively low concentrations of salts or the acid (e.g., 4.0 mol dm(-3) in the aqueous phase or 4.0 x 10(-2) mol dm(-3) in the whole reverse micelle system). The effects of perchlorate salts increased as Na+ < or = Li+ approximately H+ < Sr2+ < Ca2+ < Mg2+. Non-metallic salts, various tetraalkylammonium (R4N+) salts at lower concentrations, gave minor effects. The enhanced effects of metal salts on the configuration change of the cobalt(II)-halide complexes were interpreted by a further distortion of the hydrogen-bonded structure of the water in a "water pool" in the presence of salts of even relatively low concentrations. A conformation change with increasing temperature was also attributed to a further distortion of the water structure. An almost completed formation of [CoBr4]2- as well as [CoCl4]2- was attained in the reverse micelles at a low W value of 0.69 containing LiClO4 or HClO4. A partial transfer of the [CoX4]2- species from a "water pool" into the CHCl3 phase by the addition of the metal salts may be suspected. An examination of cobalt(II)-bromide complexes in dichloromethane/CTAB/H2O at W = 1.3 - 5.55 justified all the arguments concerning the chloroform systems. The Raman spectra of D2O containing concentrated LiBr and LiClO4 have supplied conclusive evidence that the hydrogen-bonded structure of the bulk water is completely distorted by extremely concentrated salts. PMID- 11783792 TI - Determination of trace amounts of boron in steel by reversed-phase high performance liquid chromatography with azomethine-H as a precolumn derivatizaion agent. AB - The determination of trace amounts of boron in steel by reversed-phase high performance liquid chromatography (HPLC) is described. As a derivatizing reagent for the HPLC determination of boron, 8-hydroxy-1-(salicylideneamino)-3,6 naphtalenedisulfonic acid (azomethine-H) was used with a spectrophotometric detection. A peak of boron-azomethine-H chelate was resolved from other peaks using an acetonitrile-water (29 + 71 m/m) eluent containing 8 x 10(-3) mol kg(-1) tetrabutylammonium bromide and 5 x 10(-3) mol kg(-1) acetate buffer (pH 5.0). The lower determination limit (10sigma) of boron was 3.3 x 10(-8) mol dm(-3) for a solution injected into HPLC, which is translated to 0.09 microgB/g when 0.1 g of a steel sample was subjected to the analysis. The analytical results of certified steel samples were in good agreement with the guaranteed values. The addition of ethylenediamine-N,N,N',N'-tetraacetate as a masking agent for the iron(III) matrix with the optimized eluent enables one to achieve the direct determination of trace amounts of boron in such steel sample solutions without any tedious matrix removal or preconcentration. PMID- 11783793 TI - Determination of hydrogen peroxide by iron(III) complex of thiacalix[4]arenetetrasulfonate on a modified ion-exchanger with peroxidase-like catalytic activity. AB - An iron(III) complex of thiacalix[4]arenetetrasulfonate on a modified anion exchanger (Fe3+-TCAS(A-500)) has shown high peroxidase-like activity at pH 5 - 6 for the reaction of quinoid-dye formation between 3-methyl-2-benzothiazolinone hydrazone and N-(3-sulfopropyl)aniline in the presence of hydrogen peroxide. Utilizing the peroxidase-like activity of Fe3+-TCAS(A-500) for this reaction, a method using Fe3+-TCAS(A-500) was applied for the spectrophotometric determination of hydrogen peroxide. The calibration curve by the method using Fe3+-TCAS(A-500) was linear over the range from 1 to 10 microg of hydrogen peroxide in a 1 ml sample solution. The apparent molar absorptivity for hydrogen peroxide was 2.4 x 10(4) l mol(-1) cm(-1). which was about 80% of that by peroxidase under the same conditions. This determination method of hydrogen peroxide using Fe3+-TCAS(A-500) was applied for the determination of glucose in diluted normal and abnormal control serum I and II. PMID- 11783794 TI - Determination of phosphorus based on the formation of a reduced keggin-type 12 molybdophosphate complex in an aqueous-organic solution. AB - A very simple, easy and sensitive spectrophotometric manual determination method of phosphorus for the P04(3-) ion, based on the formation of the reduced 12 molybdophosphate complex, was developed. The effect of the kind of water-miscible organic solvent and the concentration of organic solvent, ascorbic acid and HCl on the formation of the complex was investigated. The optimum determination condition was confirmed based on these results. In an aqueous-CH3CN solution, a P PO4(3-) of 0.01-20 mg l(-1) could thus be determined. It was noted that the determination range of this study was wider than that of the phosphoantimonylmolybdenum blue method (0.032-1 mg l(-1)). The effect of foreign ions on the absorbance was examined. The P-PO4(3-) in river water and seawater sampled in Kochi was determined by this method. The results were also compared with those of the phosphoantimonylmolybdenum blue method and capillary electrophoresis with an indirect detection method using K2CrO4. PMID- 11783795 TI - A kinetic method for the determination of nitrite by its catalytic effect on the oxidation of chlorpromazine with nitric acid. AB - A catalytic spectrophotometric method for the determination of trace amounts of nitrite is proposed. In acidic solution, chlorpromazine (CP) is oxidized by nitric acid to form a red compound, which is further oxidized to a colorless compound. The reaction is accelerated by trace amounts of nitrite and can be followed by measuring the absorbance at 525 nm: nitrite ion is regenerated and multiplied by nitric acid. The absorbance of the reaction increased with an increase in the reaction time, reached a maximum and decreased rapidly. Since the time required for the absorbance to reach the maximum decreased with increasing nitrite concentration, this value was used as the measured parameter for the nitrite determination. Under the optimum experimental conditions (2.3 M nitric acid, 1.2 x 10(-5) M CP, 40 degrees C), nitrite can be determined in the range 0 100 microg l(-1). The relative standard deviations (n = 6) are 4.7 and 1.8% for 40 and 100 microg l(-1) nitrite, respectively. The detection limit of this method (3sigma) is 1.2 microg l(-1). This method was successfully applied to a determination of nitrite in natural water samples. PMID- 11783796 TI - High-resolution spectra of bromo methane and methyl bromide obtained by a continuously tunable 10-bar CO2 laser based photoacoustic spectrometer. AB - High resolution spectral data of 100 ppmV (10(-6) per volume) concentrations of the trace gases bromo methane (BM, CH3Br), and methyl bromide (DME, (CH3)2O), buffered in synthetic air (80% N2, 20% O2) at atmospheric pressure and room temperature are reported. The spectra are recorded with a continuously tunable 10 bar CO2 laser based photoacoustic (PA) spectrometer. The tuning range covers 76 cm(-1) between 9.2 microm (1087 cm(-1)) and 10.7 microm (935 cm(-1)) at a constant narrow line-width of 0.018 cm(-1) (540 MHz). The non-resonant PA measuring cell employs an in-line 10-microphone array. The estimated detection limits for BM and DME are approximately 2 ppmV for a signal-to-noise ratio (SNR) of 3. This corresponds to a calculated detection limit of approximately 76 ppbV for ethylene. PMID- 11783797 TI - Development of a direct competitive microcystin immunoassay of broad specificity. PMID- 11783798 TI - Fluorescence determination of hydrogen peroxide using hemoglobin as a mimetic enzyme of peroxidase. PMID- 11783800 TI - Extraction equilibria of uni- and bivalent metal picrates with 15,15-dimethyl-16 crown-5 in benzene/water system. PMID- 11783799 TI - Selective recognition of endocrine disruptors by fluorogenic gamma-cyclodextrin having pyrene-tosyl substituents on hetero rims. PMID- 11783801 TI - Simultaneous determination of phosphate and silicate by first-derivative spectrophotometry. PMID- 11783802 TI - New orthorhombic form of 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid (diclofenac acid). PMID- 11783803 TI - Crystal and molecular structure of (-)-17-hydroxy-neo-clerod-3-en-15-oic acid from Gymnosperma glutinosum. PMID- 11783804 TI - Crystal structure of Bi(III) complex of a pyridine containing self-assembling system. PMID- 11783806 TI - Crystal structure of 3,4-diphenyl-N-cyclohexylpyrrole-2,5-dione. PMID- 11783805 TI - Crystal structure of 1,3,4-triphenyl-pyrrole-2,5-dione. PMID- 11783807 TI - Combining somatic and psychosocial treatment for chronic pain patients: perhaps 1 + 1 does = 3. PMID- 11783808 TI - Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature. AB - OBJECTIVE: To assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain. DESIGN: Systematic review of the literature. METHODS: Extensive search of several electronic databases located both controlled and uncontrolled studies. Efficacy was assessed through meta analysis of randomized controlled trials (RCTs), whereas the effectiveness of gabapentin in uncontrolled studies was assessed via a novel system of dichotomous classification of "bad" versus "good" results. FINDINGS: Thirty-five papers involving 727 patients with multiple neuropathic pain conditions met the inclusion criteria. The meta-analysis of the 2 high-quality, placebo-controlled RCTs showed positive effect of gabapentin in diabetic neuropathy and post herpetic neuralgia. The addition of 2 low-quality, placebo-controlled RCTs did not alter the magnitude or direction of observed effect. The uncontrolled studies demonstrated positive effect on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain; highest dose administered and rate-of-dose escalation showed wide variability between prescribers. Fewer and less severe side effects were reported in the uncontrolled studies. CONCLUSIONS: Gabapentin seems to be effective in multiple painful neuropathic conditions. The variable prescribing patterns of the uncontrolled studies raise the suspicion that effectiveness may be reduced if one limits administration of the drug to very low doses, whereas rapid dose escalation may be associated with increased central nervous system side effects. Well-designed controlled trials may provide insight into differential symptom sensitivity to the drug. PMID- 11783809 TI - Acupuncture for chronic low back pain: a randomized placebo-controlled study with long-term follow-up. AB - OBJECTIVE: The authors sought to determine whether a series of needle acupuncture treatments produced long-term relief of chronic low back pain. DESIGN: A blinded placebo-controlled study with an independent observer. The patients were randomized to receive manual acupuncture, electroacupuncture, or active placebo (mock transcutaneous electrical nerve stimulation). Subjects were examined and monitored by an investigator who was blinded to the treatment given. SETTING: A tertiary-level pain clinic at a Swedish university hospital. PATIENTS: Fifty consecutive patients (33 women, 17 men; mean age, 49.8 years) with chronic low back pain (mean pain duration, 9.5 years) and without rhizopathy or history of acupuncture treatment were included in the study. INTERVENTIONS: Treatments were given once per week for 8 weeks. Two further treatments were given during the follow-up assessment period of 6 months or longer. OUTCOME MEASURES: The independent observer made a global assessment of the patients 1, 3, and 6 months after treatment. The patients kept pain diaries to score pain intensity twice daily, analgesic intake, and quality of sleep daily, and activity level weekly. RESULTS: At the 1-month independent assessment, 16 of 34 patients in the acupuncture groups and 2 of 16 patients in the placebo group showed improvement (p <0.05). At the 6-month follow-up assessment, 14 of 34 patients in the acupuncture groups and 2 of 16 patients in the placebo group showed improvement (p <0.05). A significant decrease in pain intensities occurred at 1 and 3 months in the acupuncture groups compared with the placebo group. There was a significant improvement in return to work, quality of sleep, and analgesic intake in subjects treated with acupuncture. CONCLUSIONS: The authors found a long-term pain-relieving effect of needle acupuncture compared with true placebo in some patients with chronic nociceptive low back pain. PMID- 11783810 TI - Central hypersensitivity in chronic pain after whiplash injury. AB - OBJECTIVE: The mechanisms underlying chronic pain after whiplash injury are usually unclear. Injuries may cause sensitization of spinal cord neurons in animals (central hypersensitivity), which results in increased responsiveness to peripheral stimuli. In humans, the responsiveness of the central nervous system to peripheral stimulation may be explored by applying sensory tests to healthy tissues. The hypotheses of this study were: (1) chronic whiplash pain is associated with central hypersensitivity; (2) central hypersensitivity is maintained by nociception arising from the painful or tender muscles in the neck. DESIGN: Comparison of patients with healthy controls. SETTING: Pain clinic and laboratory for pain research, university hospital. PATIENTS: Fourteen patients with chronic neck pain after whiplash injury (car accident) and 14 healthy volunteers. OUTCOME MEASURES: Pain thresholds to: single electrical stimulus (intramuscular), repeated electrical stimulation (intramuscular and transcutaneous), and heat (transcutaneous). Each threshold was measured at neck and lower limb, before and after local anesthesia of the painful and tender muscles of the neck. RESULTS: The whiplash group had significantly lower pain thresholds for all tests. except heat, at both neck and lower limb. Local anesthesia of the painful and tender points affected neither intensity of neck pain nor pain thresholds. CONCLUSIONS: The authors found a hypersensitivity to peripheral stimulation in whiplash patients. Hypersensitivity was observed after cutaneous and muscular stimulation, at both neck and lower limb. Because hypersensitivity was observed in healthy tissues, it resulted from alterations in the central processing of sensory stimuli (central hypersensitivity). Central hypersensitivity was not dependent on a nociceptive input arising from the painful and tender muscles. PMID- 11783811 TI - Quantitative sensory testing in fibromyalgia patients and in healthy subjects: identification of subgroups. AB - OBJECTIVE: To determine perception and pain thresholds in patients with fibromyalgia syndrome and in healthy controls, and to investigate whether patients with fibromyalgia syndrome can be grouped with respect to thermal hyperalgesia and whether these subgroups differ from healthy controls and in clinical appearance. DESIGN: The authors conducted a quasi-experimental clinical study. SUBJECTS: Twenty-nine women patients with fibromyalgia syndrome and 21 healthy pain-free age-matched women participated in the study. METHODS: Quantitative sensory testing using a Thermotest instrument was performed on the dorsum of the left hand. Sleep and pain intensity were rated using visual analog scales. RESULTS: Cold and heat pain but not perception thresholds differed significantly between patients with fibromyalgia syndrome and healthy subjects. Based on thermal pain thresholds, two subgroups could be identified in fibromyalgia syndrome using cluster analysis. CONCLUSION: Patients with fibromyalgia syndrome were subgrouped by quantitative sensory testing (i.e., thermal pain thresholds). Subgroups show clinical differences in pain intensities, number of tender points, and sleep quality. Cold pain threshold was especially linked to these clinical aspects. PMID- 11783812 TI - High-concentration tetracaine for the management of trigeminal neuralgia: quantitative assessment of sensory function after peripheral nerve block. AB - OBJECTIVE: This study examined the effects of peripheral nerve block with high concentration tetracaine for the management of trigeminal neuralgia, and evaluated sensory function by measuring the postblock current perception threshold. METHODS: Five infraorbital nerve blocks were performed in five elderly patients using 4% tetracaine dissolved in saline or 0.5% bupivacaine. The authors used a neurometer to compare postblock current perception threshold between the block side and the contralateral healthy side, and used cold tests to assess the sensory level. RESULTS: The analgesic effect of tetracaine blocks continued for a median period of 2 months (range, 1.5-months). Hypesthesia was observed in all patients after the block but resolved within a mean period of 2.2 weeks. Although differences in current perception threshold values between sides were not significant in any patient, block-side values in two patients were clinically higher than contralateral-side values (250 vs. 5 Hz) for some time before returning to normal levels. CONCLUSION: Peripheral nerve block with high concentration tetracaine is a relatively safe and useful technique in the management of trigeminal neuralgia, particularly among older patients and those with systemic problems. PMID- 11783813 TI - Chemical sympathectomy for neuropathic pain: does it work? Case report and systematic literature review. AB - OBJECTIVE: To determine if chemical sympathectomy successfully reduces limb neuropathic pain. DESIGN: Systematic literature review of the effectiveness of phenol or alcohol sympathectomy for extremity neuropathic pain. PATIENT: A 29 year-old female with complex regional pain syndrome of both lower extremities after back surgery who was submitted to bilateral lumbar chemical sympathectomy. SEARCH STRATEGY: The Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, Medline, and EMBASE were systematically searched. OUTCOME MEASURES: (1) For the patient in question: spontaneous pain, allodynia, pinprick hyperalgesia, pressure evoked pain; (2) For the literature review: meaningful versus nonmeaningful pain relief based on degree and duration (>2 weeks) of pain relief. RESULTS: (1) The case reported experienced partial temporary relief of pain primarily related to selective modulation of allodynia, but not deep pain or pinprick hyperalgesia; (2) 44% of 66 patients in 13 studies that met the authors' inclusion criteria experienced meaningful pain relief. Whereas 19% experienced no meaningful relief, for the remaining 37% of the patients no conclusions regarding duration and degree of relief could be drawn due to poor reporting of outcomes. CONCLUSIONS: Based on the case reported and systematic literature review, chemical sympathectomy seems to have at best a temporary effect, limited to cutaneous allodynia. Despite the popularity of chemical sympatholysis, only few patients and poorly defined outcomes are reported in the literature, substantiating the need for well-designed studies on the effectiveness of the procedure. PMID- 11783814 TI - Headache continuum: concept and supporting evidence from recent study of chronic daily headache. AB - A headache continuum on the basis of the dynamic nature of headache is presented, with episodic headaches developing into daily headaches and vice versa. The concept is supported by evidence from recent study of (gradual-onset) chronic daily headache. PMID- 11783815 TI - Depression and functional disability in chronic pediatric pain. AB - OBJECTIVES: The primary aim of this study was to describe pain characteristics, coping strategies, depression, and functional disability in children and adolescents with chronic pain and to examine potential factors that are associated with functional disability in a pediatric pain population. The secondary aim of this study was to compare functional disability in two chronic pain conditions: localized musculoskeletal pain and chronic daily headaches. SUBJECTS: The participants in this study were 73 pediatric pain patients with a variety of chronic pain conditions. Subjects in the second part of the study were a subset of patients (N = 44) from the pain clinic sample with chronic localized musculoskeletal pain and a subset of patients (N = 38) from the headache center of the same hospital who had chronic daily headaches. DESIGN: Patients completed self-report measures of pain intensity, depression, coping strategies, coping efficacy, and functional disability. RESULTS: Results indicated that chronic pain had a substantial impact on the children's lives and that depression was strongly associated with functional disability. Maladaptive coping was correlated with depression and disability; however, maladaptive coping was not independently associated with functional disability. A comparison between the two groups found significant differences in pain intensity and functional disability. The localized musculoskeletal pain group reported higher levels of disability and more difficulty coping than the chronic daily headache group. CONCLUSIONS: The implications for treatment of chronic pain in children are discussed with an emphasis on greater attention to developmental issues and their relation to coping, emotional functioning, and disability in pediatric pain. Further research examining differences in coping and disability between different pediatric pain groups is also warranted. PMID- 11783816 TI - Relations between behavioral and cardiac autonomic reactivity to acute pain in preterm neonates. AB - OBJECTIVE: The purpose of this study was to assess relations and concordance between behavioral and physiologic reactivity to pain in preterm neonates at 32 weeks postconceptional age as a function of gestational age at birth. SETTING: Level III neonatal intensive care unit. DESIGN/PATIENTS: The study group comprised 136 preterm neonates (mean [range] birthweight, 1,020 g [445-1,500 g]: gestational age at birth, 28 weeks [23-32 weeks]) separated into three groups according to gestational age at birth as follows: 23 to 26 weeks (n = 48), 27 to 29 weeks (n = 52), and 30 to 32 weeks (n = 36). OUTCOME MEASURES: Reactivity to routine blood collection at 32 weeks postconceptional age was assessed using bedside-recorded behavioral and autonomic measures. Coders who were blinded to the study design scored behavioral responses (facial activity using the Neonatal Facial Coding System, sleep/waking state, and finger splay). Autonomic reactivity was assessed by change in heart rate and spectral analysis of heart rate variability (change in low-frequency and high-frequency power, and the ratio of low-frequency to high-frequency power during blood collection). RESULTS: Facial activity and state correlated moderately with change in heart rate across gestational age groups (r = 0.41-0.62). Facial activity and state did not correlate significantly with change in low-frequency and high-frequency power, or the ratio of low-frequency to high-frequency power (r = 0.00-0.31). Finger splay did not correlate with any autonomic recording (r = 0.03-0.41). Concordance between established biobehavioral measures of pain revealed individual differences. Although some neonates showed high behavioral but low physiologic reactivity, other neonates displayed the opposite reaction; however, the majority displayed concordant reactions. CONCLUSIONS: The study findings confirm the value of measuring domains independently, especially in neonates born at a very young gestational age. PMID- 11783817 TI - The role of childhood and adulthood abuse among women presenting for chronic pain management. AB - OBJECTIVE: This study investigated the association between repeated childhood and adulthood abuse and somatic symptom reporting, mental health care use, and substance use among women with chronic pain. DESIGN: A survey of a consecutive sample. PATIENTS: Ninety consecutive women patients presenting for chronic pain management at a multidisciplinary pain management center. OUTCOME MEASURES: The authors assessed the presence or absence of physical or sexual abuse (using the Drossman Physical-Sexual Abuse Survey), period of abuse, demographics, mental health care use, drug or alcohol use and substance abuse, and the presence or absence of physical, pain, and anxiety (somatic) symptoms. RESULTS: The response rate among patients surveyed was 64%. Of the 43 respondents (48%) who reported abuse, 17 (40%) cited childhood abuse, 12 (28%) cited adulthood abuse, and 14 (33%) cited repeated abuse. Women describing long-term abuse reported a significantly greater number of physical, pain, and anxiety symptoms and were more likely to report a history of substance abuse than women reporting abuse during childhood or adulthood alone. CONCLUSIONS: These data indicate a significant association between health status and reported abuse among women presenting to a multidisciplinary pain center for pain management. This finding is consistent with those of previous investigators, and emphasizes the importance of routine evaluation of the presence of long-term abuse as a possible predictor of the onset of chronic pain states. PMID- 11783818 TI - Psychometric properties of a Spanish version of the McGill Pain Questionnaire in several Spanish-speaking countries. AB - OBJECTIVE: Versions of the McGill Pain Questionnaire are available in a several languages and are used in clinical studies and sociocultural or ethnic comparisons of pain issues. However, there is a lack of studies that compare the validity and reliability of the instrument in the countries where it is used. The current study investigates the psychometric properties of a Spanish version of the McGill Pain Questionnaire in five Spanish-speaking countries. DESIGN: The authors conducted a multicenter and transnational study with one investigator in each center. Patients were evaluated once with a Spanish version of the McGill Pain Questionnaire, a visual analog scale, and a verbal rating scale. SETTING: The study was performed in pain clinics and acute pain units of four Latin American countries (Argentina, Costa Rica, Mexico, and Panama) and Spain. PATIENTS: The study included 205 patients (84 with acute pain, 121 with chronic pain) from Latin America. Their data were compared with those of 282 Spanish patients. INTERVENTIONS: The McGill Pain Questionnaire, visual analog scale, and verbal rating scale were administered once to all patients. The McGill Pain Questionnaire was administered again to patients from Latin America countries to ascertain descriptor comprehension. OUTCOME MEASURES: Demographic data, McGill Pain Questionnaire parameters, and visual analog scale and a verbal rating scale scores were obtained from patients with chronic and acute pain. Psychometric properties of the Spanish version of the McGill Pain Questionnaire were established for each country by calculating the ordinal consistency by means of rank-scale correlation (Spearman test), intercategory correlation, and interparameter correlation (Pearson test). Concurrent validity was also calculated by comparing scores from the visual analog scale (Pearson test) and verbal rating scale (Spearman test) with questionnaire parameters (qualitative-to quantitative comparisons). RESULTS: The Spanish version of the McGill Pain Questionnaire maintained a high internal validity when tested in different countries. Ordinal consistency, intercategory, interparameter, and qualitative-to quantitative parameter correlations were similar in all countries. Few descriptors were considered to be inappropriate or difficult to understand. CONCLUSIONS: The psychometric properties of the Spanish version of the McGill Pain Questionnaire assessed in different Latin-American countries suggest that the questionnaire may be used to evaluate Spanish-speaking patients. The validity of this test should be extended with reliability studies to further establish its usefulness in the evaluation of pain. PMID- 11783819 TI - A case of a methadone-induced movement disorder. AB - OBJECTIVE: To increase awareness of the possibility of opioid induced movement disorders. SETTING: A university-affiliated Veterans Affairs Hospital. PATIENT: A patient with upper extremity pain due to complex regional pain syndrome type I (reflex sympathetic dystrophy). INTERVENTIONS: Attempted pain control with methadone. RESULTS AND CONCLUSIONS: After failing many attempts at control, the authors were able to provide their patient significant pain relief from her complex regional pain syndrome type I using methadone. Unfortunately, the patient eventually developed a movement disorder, characterized by tremor, choreiform movements, and a gait abnormality, probably related to this opioid. The authors conclude that, while this type of movement disorder is uncommon, clinicians need to be aware of opioid-induced movement disorders, because they are disturbing to patients and often easily treated. PMID- 11783820 TI - Screening of patients with complex regional pain syndrome for antecedent infections. PMID- 11783821 TI - Etiology, prevention, treatment, and disability management of chronic pain. Introduction. PMID- 11783822 TI - Chronic pain and the concept of disablement. PMID- 11783823 TI - Acupuncture, transcutaneous electrical nerve stimulation, and laser therapy in chronic pain. AB - OBJECTIVE: The purpose of this review was to determine how effective acupuncture, transcutaneous electrical nerve stimulation, acupuncture-like transcutaneous nerve stimulation, laser therapy, electrical nerve stimulation, and neuroreflexotherapy are in the management of chronic pain. METHODOLOGY: The literature search identified six systematic reviews of the literature and four randomized controlled trials to provide evidence for this review. RESULTS: The systematic reviews included different methodologies and heterogeneity of study groups, but studies were generally of poor methodology. Although sham acupuncture may have analgesic effects, it was used as a control in many studies. CONCLUSIONS: In general, the evidence was contradictory or inadequate, reflecting poor study methodologies. No positive conclusion could be reached for acupuncture, transcutaneous electrical nerve stimulation, acupuncture-like transcutaneous nerve stimulation, laser therapy, or neuroreflexotherapy. A single randomized controlled trial provided limited evidence (level 3) that electrical nerve stimulation is effective for pain relief in myofascial pain syndrome for up to 4 weeks, but further study in humans is needed. Future randomized controlled trials and systematic reviews should include subgroup analyses of sham acupuncture and inert placebos as controls. PMID- 11783824 TI - Biopsychosocial approaches to the treatment of chronic pain. AB - BACKGROUND: Biopsychosocial treatments address the range of physical, psychological, and social components of chronic pain. OBJECTIVE: This review sought to determine how effective unimodal and multimodal biopsychosocial approaches are in the treatment of chronic pain. METHODOLOGY: The literature search identified three systematic reviews of the literature and 21 randomized controlled trials to provide the evidence for this review. RESULTS: The systematic reviews and 12 randomized controlled trials reported on chronic low back pain. Other randomized controlled trials studied fibromyalgia (three trials) and back or other musculoskeletal disorders (five trials). Biopsychosocial components reviewed were electromyogram feedback and hypnosis as unimodal approaches, and behavioral and cognitive-behavioral treatments and back school, or group education, as multimodal approaches for chronic low back pain. For other chronic pain disorders, cognitive-behavioral treatments were reviewed. Comparisons were hindered by studies with heterogeneous subjects, varied comparison groups, different cointerventions and follow-up times, variable outcomes, and a range of analytic methods. CONCLUSIONS: Multimodal biopsychosocial treatments that include cognitive-behavioral and/or behavioral components are effective for chronic low back pain and other musculoskeletal pain for up to 12 months (level 2). There is limited evidence (level 3) that electromyogram feedback is effective for chronic low back pain for up to 3 months. The remaining evidence of longer-term effectiveness and of effectiveness of other interventions was inadequate (level 4a) or contradictory (level 4b). Future studies of cognitive-behavioral treatments should be condition specific, rather than include patients with different pain conditions. PMID- 11783825 TI - Interventions for disability management. AB - BACKGROUND: With an increasing prevalence of low back pain, management can include modified work, work-conditioning, or work-hardening programs. Modified work programs, or employer's worksite interventions or clinic-based programs under medical supervision, provide a gradual increase of workload. Work conditioning programs, or unimodal physical conditioning and function activities, promote return to work. Work-hardening programs, or graded work simulations and psychological interventions, are used as part of an interdisciplinary program addressing physical and functional needs. OBJECTIVE: The objective of the review was to determine how effective modified work programs, work hardening, and work conditioning are in the management of chronic pain disability. METHODOLOGY: The literature search identified two systematic literature reviews to provide the evidence about these interventions for disability management. RESULTS: Studies of work conditioning showed methodological variability, heterogeneous subjects, variable definitions of modified work, and limited outcome measures. Using return to-work outcomes, 8 of the 11 studies of adequate methodological quality reported positive effects of modified work programs, mostly light duty. For work conditioning and work hardening, studies showed methodological variability combined with heterogeneous subjects, including varying times out of work and varying work ethics from different countries. Most study results were uncertain, though results of three of the four medium-quality studies were positive. CONCLUSIONS: Modified work programs may improve return-to-work rates of workers with work-related injuries for 6 months or longer (level 2). There is inadequate evidence (level 4a) to determine what particular aspects of modified work programs are helpful. Work conditioning and work hardening may or may not improve the return to work of more chronically disabled workers (level 4b). PMID- 11783826 TI - Demographic variables and chronic pain. AB - OBJECTIVE: Are demographic variables (age, gender, sex, and marital status) predictors of chronic pain and chronic pain disability? METHODOLOGY: The literature search identified one systematic review plus 12 observational studies (11 back or spinal pain and 1 whiplash) to provide evidence about this question. RESULTS: The role of predictive factors varied with different patient groups, settings, and interventions. Analytic methods also varied. Most studies evaluated age, sex, and marital status with other nondemographic variables. CONCLUSIONS: The studies provided limited and conflicting evidence (level 4b) that either increasing age or sex correlates with chronic pain and chronic pain disability. Marital status and education both showed conflicting evidence (level 4b) of a correlation with chronic pain. Age and sex express different risks for disease, severity of injury, and occupational opportunities and choices. Demographic factors can modify the effect of other factors with which they interact. Future identification of predictors of chronic pain should include control for age and gender (level 3). PMID- 11783827 TI - Medical history and chronic pain. AB - OBJECTIVE: Can either a history of previous similar injury, including recurrence of injury, or an individual's symptoms, including time off work, predict chronic pain and/or chronic pain disability? METHODOLOGY: The literature search identified one systematic review and six observational studies (5 low back pain and 1 chronic shoulder pain) to provide evidence about these questions. RESULTS: Only one study evaluated subjects before a painful event. Other studies evaluated subjects over a range of time from onset of pain, including some selected for clinic treatment. This variability as well as the use of different outcome measures without blinding limited the quality of the evidence. CONCLUSIONS: The studies provide moderate evidence (level 2) that a history of previous similar pain predicts subsequent reports of pain and limited evidence (level 3) that a history of similar pain predicts poorer outcomes after recurrent injury. The studies also provide moderate evidence (level 2) that longer duration of pain predicts the occurrence of subsequent reports of pain and limited evidence (level 3) that longer time off work before treatment predicts poorer activity and poorer participation outcomes after recurrent injury. PMID- 11783828 TI - Physical symptoms and signs and chronic pain. AB - OBJECTIVE: Do physical findings that are used to indicate location and extent of tissue damage and a measure of the severity of initial pain predict subsequent reports of pain and of disability? METHODOLOGY: A standardized literature search identified one systematic review and 12 observational studies (9 low back pain, 2 neck pain, and 1 carpal tunnel syndrome) to provide evidence about these questions. RESULTS: Most studies were of specific populations. These studies were useful studies of predictors, but they have limited generalizability. Exclusions and loss of subjects at follow-up in some studies also limited generalizability. Conclusions were made cautiously, because some factors with statistical correlations with chronic pain were not plausible predictors. CONCLUSIONS: The studies provide moderate evidence (level 2) that reports of the intensity of pain in acute musculoskeletal injury predict subsequent reports of pain. There is limited evidence (level 3) that the location and extent of injury predict reports of pain and poor functional activity outcomes. There is moderate evidence (level 2) that physical symptoms and signs cannot be considered individual predictors of chronic pain disability as measured by participation outcomes. Instead, in the transition from subacute to chronic pain disability, functional disability and psychological distress play a more important role than pain intensity. PMID- 11783829 TI - Psychological factors and the development of chronic pain. AB - OBJECTIVE: What is the role of psychological factors in chronic pain and chronic pain disability? METHODOLOGY: The literature search identified 20 observational studies to provide evidence about this question. RESULTS: Most studies evaluated psychological variables as predictors of return to work. Most studies were prospective cohort studies, including those providing the most data about etiology. In some studies, weak methods and analyses limited the conclusions. In addition, the methodologic criteria of the literature search excluded some well known reports about this subject. CONCLUSIONS: Because of the small number of studies, there was inadequate evidence that chronic pain results from a prior psychiatric disorder (level 4a). The studies provided limited evidence (level 3) that chronic depression plays a role in the development of new pain locations (although not for low back pain); that prior nervousness and past negative life events predict work disability; and that depression, anxiety, and a sense that control rests outside of one's own self may predict slower recovery from pain and disability. These findings do not prove that psychological factors have a role in the development of chronic pain. Psychological impairment may precede the onset of pain. Based on current knowledge, it may also arise as a complication of chronic pain. PMID- 11783830 TI - Employment-related factors in chronic pain and chronic pain disability. AB - BACKGROUND: Disability is a multifactorial phenomenon. Social scientists suggest that nonclinical factors, including age, education, and job status, correlate with disability. OBJECTIVE: Do employment-related factors predict chronic pain and/or chronic pain disability? METHODOLOGY: The literature search identified 15 observational studies to provide the evidence about this question. RESULTS: Review topics included job satisfaction, type of work, modified work and work autonomy, other employment-related factors, and socioeconomic status. Most subjects in the studies had low back pain. The studies used return to work as an outcome predicting chronic pain disability. CONCLUSIONS: Lack of modified work and lack of work autonomy predicted chronic pain disability (level 2). There was limited evidence (level 3) that lack of job satisfaction, perception of difficult job conditions and demands, heavy physical demands of the job, private rather than public employment, and lower socioeconomic group predict chronic pain disability. The number of years employed varied as a predictor in different studies (level 4b). PMID- 11783831 TI - Compensation and chronic pain. AB - BACKGROUND: The literature contains many different viewpoints on the impact of compensation on recovery from chronic pain. OBJECTIVE: What is the role of compensation in chronic pain and/or chronic pain disability? METHODOLOGY: The literature search identified 11 observational studies to provide evidence about this question. RESULTS: There is a paucity of high-quality data on the subject of the impact of compensation on chronic pain. This subject was reviewed under the headings of (1) injury claim rate and duration; (2) recovery; and (3) rehabilitation treatment programs. The studies were of subjects with musculoskeletal pain, mainly low back pain. CONCLUSIONS: Filing a compensation claim for costs, retaining a lawyer, or higher pain intensities were limited predictors of longer claims (level 3). As the ratio of compensation to preinjury wage increases, there is moderate evidence (level 2) that the duration of the claim increases and that disability is more likely. Compensation status, particularly combined with higher pain intensities, is associated with poorer prognosis after rehabilitation treatment programs (level 3). PMID- 11783832 TI - The concept of pain. PMID- 11783833 TI - Prevention of chronic pain: the unexplored frontier. PMID- 11783834 TI - Manipulation and mobilization in the treatment of chronic pain. AB - OBJECTIVE: The purpose of this review was to determine how effective manipulation and mobilization are in the treatment of chronic pain. METHODOLOGY: The literature search identified three systematic reviews addressing the effectiveness of manipulation and mobilization for low back pain, two systematic reviews addressing chronic neck pain, three randomized controlled trials addressing post-traumatic headache and neck pain, and one systematic review and one randomized controlled trial addressing upper limb (including shoulder) disorders. RESULTS: Most studies lacked details of the specific interventions, which were often combined with other interventions, and this could have enhanced or masked effectiveness. Subject groups were heterogeneous, and investigators did not indicate effectiveness for subgroups. Systematic reviews of chronic low back pain found evidence of effectiveness compared with placebo and with usual care. Evidence from the systematic reviews for chronic neck pain and from the systematic review and randomized controlled trial for chronic soft tissue shoulder disorders was contradictory. For post-traumatic headache, the randomized controlled trials reported a time-limited positive benefit or no different effects than comparison treatment. CONCLUSIONS: Manipulation and mobilization are more effective for chronic low back pain than placebos or usual care for up to 6 months (level 2). For chronic post-traumatic headache, evidence of effectiveness of manipulation and mobilization is limited (level 3). Manipulation and mobilization may or may not be effective for either chronic neck pain or chronic soft tissue shoulder disorders (level 4b). PMID- 11783835 TI - Exercise in the treatment of chronic pain. AB - OBJECTIVE: The purpose of this review was to determine how effective exercise is in the treatment of chronic pain. METHODOLOGY: The literature search identified three systematic reviews and three randomized controlled trials addressing the effectiveness of exercise for the management of chronic low back pain, one systematic review and one randomized controlled trial addressing chronic neck pain, two systematic reviews and three randomized controlled trials addressing upper extremity pain, and three randomized controlled trials addressing fibromyalgia. RESULTS: Randomized controlled trials were better than systematic reviews for providing details of patient subgroups and of exercise programs, but there was a general lack of evaluation of the different subgroups. The studies also failed to assess the different duration and frequency of exercise programs. For chronic low back pain, a systematic review and two of the three randomized controlled trials found exercise to be effective: other findings were uncertain. For chronic neck pain, both the systematic review and the randomized controlled trial provided generally uncertain results, with only one positive-result study in the systematic review. For upper extremity, positive effects of exercise were shown for chronic lateral epicondylitis and for specific soft tissue shoulder disorders. For fibromyalgia, two of the three randomized controlled trials showed effectiveness of exercise. CONCLUSIONS: Exercise is effective for the management of chronic low back pain for up to 1 year after treatment and for fibromyalgia syndrome for up to 6 months (level 2). There is conflicting evidence (level 4b) about which exercise program is effective for chronic low back pain. For chronic neck pain and for chronic soft tissue shoulder disorders and chronic lateral epicondylitis, evidence of effectiveness of exercise is limited (level 3). PMID- 11783836 TI - Pathophysiology of chronic pain disorders. PMID- 11783837 TI - Systemic drug treatment for chronic musculoskeletal pain. AB - OBJECTIVE: The purpose of this review was to determine how effective different classes of analgesic agents are in the management of chronic pain. METHODOLOGY: The literature search identified five systematic reviews and 18 randomized controlled trials to provide evidence about systemic drug treatment for chronic pain. RESULTS: Studies in the systematic reviews were mainly of low back pain, and studies in the randomized controlled trials were mainly of fibromyalgia. Other studies investigated of rheumatic pain, musculoskeletal pain, chronic low back pain, and temporomandibular pain. Classes of analgesic agents reviewed were antidepressants, nonsteroidal anti-inflammatory drugs, muscle relaxants, opioid analgesics, and a number of miscellaneous agents. CONCLUSIONS: For chronic pain, opioid analgesics provide benefit for up to 9 weeks (level 2). For chronic low back pain, the evidence shows that various types of nonsteroidal antiinflammatory drugs are equally effective or ineffective, and that antidepressants provide no benefit in the short to intermediate term (level 2). Muscle relaxants showed limited effectiveness (level 3) for chronic neck pain and for chronic low back pain for up to 4 weeks. For fibromyalgia, there is limited evidence (level 3) of the effectiveness of amitryptiline, ondansetron, zoldipem, or growth hormone, and evidence of no effectiveness for nonsteroidal anti-inflammatory drugs, malic acid with magnesium, calcitonin injections, or s-adenyl-L-methionine. For temporomandibular pain, oral sumatriptan is not effective (level 2). The remaining evidence was inadequate (level 4a) or contradictory (level 4b). PMID- 11783838 TI - Injections and surgical therapy in chronic pain. AB - OBJECTIVE: The purpose of this review was to determine how effective surgery and injection therapy are in the management of chronic pain. METHODOLOGY: A standardized literature search identified seven systematic reviews of the literature and six randomized controlled trials to provide evidence about surgery and injection therapy for chronic pain. RESULTS: Some study subjects had highly specific diagnoses, whereas other study subject groups had nonspecific pain, including multiple conditions. The timing of treatment interventions was generally unclear, and few studies analyzed subgroups. Overall, there was a lack of methodologically sound studies of surgery and injection therapies. CONCLUSIONS: Standard discectomy compared with conservative treatment for proven disc herniation (< or = 1 year) and local triamcinolone injection for lateral epicondylitis (< or = 12 weeks) are both effective for pain relief (level 2). There was limited evidence of effectiveness (level 3) of intraoperative steroid at discectomy, epidural steroid injection for sciatica with low back pain, caudal steroid injection for low back pain, local glycosaminoglycan polyphosphate injection for lateral epicondylitis, intraarticular steroid injection for shoulder arthritis, subacromial steroid injections for rotator cuff tendinitis, nonspecific injections for painful shoulder, systemic growth hormone for fibromyalgia, and intravenous adenosine for fibromyalgia. There was limited evidence (level 3) that there is no additional benefit of adding steroid to local anesthetic in caudal epidural injections. There is limited evidence (level 3) that intravenous adenosine is ineffective for fibromyalgia. The remaining evidence was inadequate (level 4a) or contradictory (level 4b). PMID- 11783839 TI - History of modern genetics in Germany. AB - The history of modern genetics in Germany during the 20th century is a story of missed chances. In the USA the genetic revolution opened a fascinating new field for ambitious scientists and created a rapidly growing new industry. Meanwhile Germany stood aside, combating with political and social restrictions. Promising young scientists who wanted to work in the field left Germany for the US, and big companies moved their facilities out of the country. Up until the middle of the 1990s molecular biology in Germany remained a "sleeping beauty" even though many brilliant scientists did their jobs very well. Then a somewhat funny idea changed everything: the German minister for education and science proclaimed the BioRegio contest in order to award the most powerful biotechnology region in Germany concerning academia and especially industry. Since then Germany's biotechnology industry has grown constantly and rapidly due to the foundation of a number of small biotech companies; big companies have returned their interests and their investments to Germany, paralleled by an improvement in academic research because of more funding and better support especially for younger scientists. In respect to biotechnology and molecular biology, Germany is still a developing country, but it has started to move and to take its chances in an exciting global competition. PMID- 11783840 TI - Enzyme catalysis in reverse micelles. AB - Water in oil microemulsions with reverse micelles provide an interesting alternative to normal organic solvents in enzyme catalysis with hydrophobic substrates. Reverse micelles are useful microreactors because they can host proteins like enzymes. Catalytic reactions with water insoluble substrates can occur at the large internal water-oil interface inside the microemulsion. The activity and stability of biomolecules can be controlled, mainly by the concentration of water in these media. With the exact knowledge of the phase behaviour and the corresponding activity of enzymes the application of these media can lead to favourable effects compared to aqueous systems, like hyperactivity or increased stability of the enzymes. PMID- 11783841 TI - Perspectives in liquid membrane extraction of cephalosporin antibiotics. AB - In this paper an overview of the developments in liquid membrane extraction of cephalosporin antibiotics has been presented. The principle of reactive extraction via the so-called liquid-liquid ion exchange extraction mechanism can be exploited to develop liquid membrane processes for extraction of cephalosporin antibiotics. The mathematical models that have been used to simulate experimental data have been discussed. Emulsion liquid membrane and supported liquid membrane could provide high extraction flux for cephalosporins, but stability problems need to be fully resolved for process application. Non-dispersive extraction in hollow fiber membrane is likely to offer an attractive alternative in this respect. The applicability of the liquid membrane process has been discussed from process engineering and design considerations. PMID- 11783842 TI - Biosynthesis of triterpenoid saponins in plants. AB - Many different plant species synthesise triterpenoid saponins as part of their normal programme of growth and development. Examples include plants that are exploited as sources of drugs, such as liquorice and ginseng, and also crop plants such as legumes and oats. Interest in these molecules stems from their medicinal properties, antimicrobial activity, and their likely role as determinants of plant disease resistance. Triterpenoid saponins are synthesised via the isoprenoid pathway by cyclization of 2,3-oxidosqualene to give primarily oleanane (beta-amyrin) or dammarane triterpenoid skeletons. The triterpenoid backbone then undergoes various modifications (oxidation, substitution and glycosylation), mediated by cytochrome P450-dependent monooxygenases, glycosyltransferases and other enzymes. In general very little is known about the enzymes and biochemical pathways involved in saponin biosynthesis. The genetic machinery required for the elaboration of this important family of plant secondary metabolites is as yet largely uncharacterised, despite the considerable commercial interest in this important group of natural products. This is likely to be due in part to the complexity of the molecules and the lack of pathway intermediates for biochemical studies. Considerable advances have recently been made, however, in the area of 2,3-oxidosqualene cyclisation, and a number of genes encoding the enzymes that give rise to the diverse array of plant triterpenoid skeletons have been cloned. Progress has also been made in the characterisation of saponin glucosyltransferases. This review outlines these developments, with particular emphasis on triterpenoid saponins. PMID- 11783843 TI - Three-phase oxygen absorption and its effect on fermentation. AB - The absorption rate of oxygen in the presence of a second, dispersed, organic phase can be significantly increased due to the higher solubility and diffusivity of oxygen in the organic phase. The oxygen supply of micro-organisms, which is very often a limiting factor during fermentation, can be improved, and the critical level of oxygen in the fermentation broth can be avoided by using dispersed organic phase. This paper reviews the models of the enhanced absorption rates and their integration into mass balance equations of fermentation. Several calculations were carried out to illustrate the effect of the dispersed organic phase and kinetic parameters on the absorption rates and on fermentation with double-substrate-limitation kinetics applying batch and continuous operation modes. Using software taking from the literature, the effect of the organic phase on the baker's yeast production is also presented in fed-batch mode. PMID- 11783844 TI - Microbial sensors on a respiratory basis for wastewater monitoring. AB - In respect of their rapidity, their online capabilities, and their moderate costs, biosensing systems generally offer an attractive alternative to the existing methods of water analysis. Additionally, one particular advantage of microbial biosensors is the ability to measure direct effects on living cells, e.g., their respiratory activity and its alteration caused by environmental pollutants. It is true that microbial sensors, often do not provide the optimum solution for the determination of individual analytes when compared to established physico-chemical analysis methods. However, these biosensing devices are predestined for the summary determination of environmentally relevant compounds and their complex effects, respectively. For this reason, microbial sensors allow an integral evaluation of the degree of environmental pollution including the interaction of various compounds. Moreover, in some cases specific metabolic pathways in microorganisms are used, resulting in the development of microbial sensors for the more selective analysis for those compounds or pollutants, which cannot be measured by simple enzyme reactions, e.g., the determination of aromatic compounds and heavy metals. This chapter gives an overview of microbiological biosensors on respiratory basis for the measurement of the following environmentally relevant compounds: inorganic N-compounds, heavy metals, organic xenobiotics and the estimation of sum parameters or so-called complex parameters such as BOD, ADOC, N-BOD, and the inhibition of nitrification. PMID- 11783845 TI - Risk perception. PMID- 11783847 TI - On target cell numbers in radiation-induced H4-RET mediated papillary thyroid cancer. AB - Radiation-induced human papillary thyroid cancer (PTC) is associated with chromosomal inversions that involve the genetic loci H4 and RET on chromosome 10. Recently, experimental data has shown that these loci lie in very close spatial proximity in a high proportion of adult human thyroid cells. Applying the generalized formulation of dual radiation action to this H4-to-RET geometric distance data, we predict here the radiation dose-response of H4-RET induction. The predicted H4-RET dose-response has a linear-to-quadratic transition dose of approximately 7 Gy, suggesting the validity of linear risk extrapolations to very low doses for H4-RET mediated radiation-induced PTC. In conjunction with A-bomb survivor data, the predicted H4-RET dose-response yields estimates of the number of PTC target cells that are of the order of approximately 10(6) to approximately 10(7) cells, i.e. considerably less than the total number of follicular cells in the thyroid gland. PMID- 11783846 TI - Radiotherapy of childhood haemangiomas: from active treatment to radiation risk estimates. AB - Childhood skin haemangiomas have been subjected to many different kinds of active treatment. From the beginning of the twentieth century and up to 1960-1970, radiotherapy maintained a dominating place in this treatment, although during the latter part of this period its role was more and more questioned. Starting in 1958, I felt that, based on the scientific literature and on my own observations at Malmo University Hospital, active therapy including radiotherapy should be abandoned since it had turned out to be unnecessary and, furthermore, could be harmful. This viewpoint resulted from an increased knowledge of the natural history of the disease. I then got the possibility to establish a follow-up study cohort at Sahlgrenska University Hospital in Goteborg with the aim of gaining information on early and late radiation effects following childhood radiotherapy. Later, the study cohort was enlarged by pooling with similar cohorts originating from Stockholm and Paris. A summary of the results of the epidemiological studies is also presented here. This historical overview reflects half a century of radiation therapy and radiation protection philosophy. It contains a basic message pointing to the value of proper and reliable collection of medical data and to the importance of local, regional and national registers, to preserve the information. PMID- 11783848 TI - Monte Carlo simulations and measurement of DNA damage from x-ray-triggered auger cascades in iododeoxyuridine (IUdR). AB - We investigated the DNA damage from Auger electrons emitted from incorporated stable iodine (127I), following photoelectric absorption of external x-rays. The effectiveness of the Auger electrons in producing DNA double-strand breaks (DSB) was determined theoretically, using Monte Carlo simulations of the radiation physics and chemistry, and was shown to be in reasonable agreement with DNA damage measured using the comet assay. The DSB yields were measured in CHO cells for 60Co (as a non-Auger-promoting radiation) and for tungsten-filtered 100 kVp x rays capable of producing Auger electron emission. The theoretical study showed that on average, 2.5 Auger electrons were emitted for N-shell orbital vacancies and up to 10 Auger electrons were emitted from L1-shell vacancies. These Auger bursts produced approximately 0.03 DSB per N-shell vacancy and 0.3 DSB per K shell or L-shell vacancy. The calculated yield of DSB from Auger cascades per unit dose (1 Gy) in water was approximately 1.7 for tungsten-filtered 100 kVp x rays, assuming 20% IUdR substitution of thymidine. The comet assay yielded an experimental value of 3.6+/-1.6 per 1 Gy for the same conditions. The Monte Carlo simulations also demonstrated a high complexity of DSB produced by Auger cascades with virtually all DSB from inner shell orbitals (i.e. K, L shells) accompanied by compounded strand breakage and base damage, indicating a difficult lesion to repair. This finding agrees well with comet assay results of DNA repair, where an increase in the DSB yield in IUdR-sensitized cells was shown to persist after a time of 24 h. We conclude that Auger cascades in iodine produce a modest increase in the number of initial strand breaks of the order of 10% but the complex nature of these DSB makes them very difficult to repair or potentially prone to misrepair. The accentuated DNA damage may have major consequences for cell survival and may be exploitable in kilovoltage photon activation therapy (PAT) of tumors sensitized with iodine. PMID- 11783849 TI - Microdosimetric calculation of absorption fraction and the resulting dose conversion factor for radon progeny. AB - It is an established fact that radon progeny can induce lung cancers. However, there is a well-known discrepancy between the epidemiologically derived dose conversion factor for radon progeny (4 mSv/WLM) and the dosimetrically derived value (15 mSv/WLM) (mSv is a unit of the dose while WLM is a unit of exposure to radon progeny). Up to now there is no satisfactory explanation to this. In the present study we propose that microdosimetry will help reduce the discrepancy significantly. The ICRP Human Respiratory Tract Model (HRTM) has been applied to calculate the effective dose conversion factor. All parameters have been kept at their best estimates. Modifications were made in the calculation of the absorbed fractions of alpha particles. In contrast to the ICRP approach where the energy has been considered to be deposited in the layer containing the sensitive cells, we used a microdosimetric approach in which the alpha particles deposit their energy only in the nuclei of sensitive cells. This modification alone has lowered the dose conversion factor by about one-third (from 15 mSv/WLM down to approximately 10 mSv/WLM). PMID- 11783850 TI - Micro-organisation of the membrane after radiation-induced apoptosis: a flow cytometry study. AB - The aim of this study was to detect membrane fluidity modifications in blood lymphocytes that had been exposed to gamma-radiation, at a graded series of depths from the surface to the centre of the membrane bilayer and as a function of cell viability. A time course was performed to verify the contribution of the membrane to radiation-induced apoptosis. In comparison with spectrofluorimetry, flow cytometry proved to be a reliable method for measuring radiation-induced membrane alterations. Late apoptotic lymphocytes were characterised by a significant decrease of the 3-SA, 6-SA and 9-SA fluorescence anisotropy values, compared to viable lymphocytes. Moreover, a highly significant difference was observed in the early apoptotic lymphocyte subpopulation between the fluorescence anisotropy values measured 24 h (radiation-induced apoptosis) and those measured 1 h (spontaneous apoptosis) after irradiation. The simultaneous assessment of cellular viability and membrane fluidity using n-(9-anthroyloxy) fatty acid probes, may be relevant for the investigation of interactions which may exist between membrane modifications and the apoptotic process. Our observations support the specificity of radiation-induced apoptosis compared to spontaneous apoptosis in terms of biophysical modifications of membrane properties. PMID- 11783851 TI - Effect of fractionated exposure to carbon ions on the frequency of chromosome aberrations in tobacco root cells. AB - The induction of chromosome aberrations in tobacco root tip cells was measured after exposure to either 18 MeV/n carbon ions or 2 MeV electrons. The RBE value for acute exposure was found to be about 10. Splitting the dose into two fractions did not produce any significant effect on the yield of aberrations following carbon-ion exposure, whereas a clear decrease was observed after exposure to electrons thereby indicating an induction/activation of error-free repair after the first fraction. Moreover, this decrease appeared to be independent of the types of chromosome aberrations. On the other hand, it was suggested that the lack of any significant effect on the yield of aberrations is either due to a lack of error-free repair or to a less efficient damage repair after exposure to carbon ions. PMID- 11783852 TI - Temporal and spatial prediction of radiocaesium transfer to food products. AB - A recently developed semi-mechanistic temporal model is used to predict food product radiocaesium activity concentrations using soil characteristics available from spatial soil databases (exchangeable K, pH, percentage clay and percentage organic matter content). A raster database of soil characteristics, radiocaesium deposition, and crop production data has been developed for England and Wales and used to predict the spatial and temporal pattern of food product radiocaesium activity concentrations (Bq/kg). By combining these predictions with spatial data for agricultural production, an area's output of radiocaesium can also be estimated, we term this flux (Bq/year per unit area). Model predictions have been compared to observed data for radiocaesium contamination of cow milk in regions of England and Wales which received relatively high levels of fallout from the 1986 Chernobyl accident (Gwynedd and Cumbria). The model accounts for 56% and 80% of the observed variation in cow milk activity concentration for Gwynedd and Cumbria, respectively. Illustrative spatial results are presented and suggest that in terms of food product contamination areas in the North and West of England and Wales are those most vulnerable to radiocaesium deposition. When vulnerability is assessed using flux the spatial pattern is more complex and depends upon food product. PMID- 11783853 TI - Migration of fallout-radionuclides in the soil: effect of non-uniformity of the sorption properties on the activity-depth profiles. AB - Experimentally observed activity-depth profiles of fallout radionuclides in the soil frequently exhibit a comparatively fast moving tail in soil layers below the peak concentration (tailing). Monte Carlo calculations on the basis of the convection-dispersion model show that this phenomenon can be explained by assuming that either the hydraulic properties of the soil (characterised by the diffusion/dispersion coefficient and pore water velocity) or the sorption properties of the soil (characterised by the distribution coefficient Kd), or both, exhibit a horizontal variability according to a log-normal distribution. Modifications of the activity-depth profile due to a Kd value which decreases linearly with depth were examined by using a random walk approach, based also on the convection-dispersion model. In this case, however, a pronounced tailing effect of the activity-depth profile did not result. Interpretation and realistic modelling of an experimentally observed activity-depth profile which exhibits a tailing effect is thus not unambiguously possible without any additional information on the spatial variability of the hydraulic parameters and, independently, also for the sorption properties. PMID- 11783854 TI - The relationship between the RBE of alpha particles and the radiosensitivity of different mutations of Chinese hamster cells. AB - The RBE of alpha-particles in different mutations of Chinese hamster cells was determined with the aim of identifying differences in the sensitivity to x-ray and alpha-particle-induced DNA damage. Two parental lines of Chinese hamster cells and four radiosensitive mutants were irradiated with different single doses of x-rays and alpha-particles and clonogenic cell survival was determined. Radiosensitivity to x-rays varied by a factor of 5 between the cell strains whereas sensitivity to alpha-particle irradiation was almost identical among all strains. The RBE is only determined by the sensitivity of the cells towards x rays. Since cells with different defects of repair or cell cycle control have different radiosensitivities, we conclude that the effects of x-ray irradiation and the RBE are mostly determined by the activity of repair processes. PMID- 11783855 TI - International pesticide use. Introduction. PMID- 11783856 TI - Pesticide exports from U.S. ports, 1997-2000. AB - U.S. Customs records reveal that 3.2 billion pounds of pesticide products were exported in 1997-2000, an average rate of 45 tons per hour. Nearly 65 million pounds of the exported pesticides were either forbidden or severely restricted in the United States; however, no banned pesticide export was recorded for the year 2000. 2.2 million pounds of pesticides regulated under a treaty on persistent organic pollutants (POPs) were exported between 1997 and 1999, with no such export in 2000. Exports of pesticides subject to the prior informed consent (PIC) treaty decreased 97% from the 1997 total of nearly 3 million pounds. Thus, international efforts to reduce the trade in hazardous pesticides may be bearing fruit. However, they are balanced by high rates of export of pesticides designated "extremely hazardous" by the WHO (89 million pounds), pesticides associated with cancer (170 million pounds), and pesticides associated with endocrine disrupting effects (368 million pounds), mostly to developing countries. These findings point in two directions: first, progress is possible, and second, the focus of international efforts should be expanded. From public health and environmental protection perspectives, exports of hazardous pesticides remain unacceptably high. PMID- 11783857 TI - Paraquat in developing countries. AB - The herbicide paraquat is considered safe by industry and the bulk of regulators worldwide. However, determinants of exposure from 30 years ago persist in developing countries. Little is known about systemic absorption from occupational exposures. The relationships between exposure determinants, levels of external exposure, biomarkers of exposure, and outcomes are not clear. High rates of severe acute poisonings have been documented. In addition, topical injuries occur in as many as 50% of exposed workers. Non-worker populations are also at risk, particularly children. Long-term and delayed health effects include Parkinson's disease, lung effects, and skin cancer. Regulatory agencies have not fully recognized either the inherent toxicity of paraquat or the particular risks derived from exposures in developing countries. Independent risk assessment in the developing-country context and application of the precautionary principle are necessary to prevent adverse effects of dangerous pesticides in susceptible populations. PMID- 11783858 TI - Hazardous pesticides in Central America. AB - Pesticides are an extensively documented occupational and environmental hazard in Central America. Yet, severe problems persist. Toxic pesticide use in the Region increased during 1985-1999. High exposure levels and ineffectiveness of personal protective equipment evidence the difficulties for risk reduction. Acute poisonings remain a severe problem. Delayed and/or long-lasting health effects include dermatoses, cancer, and genotoxic, neurotoxic, and respiratory effects. The use of hazardous pesticides persists through deficiencies in government driven assessment and risk management; excessive focus on regional harmonization; short-term economic interests; strong links between industry and governments; aggressive marketing; weak trade unions; and failure of universities to reach decision makers. Regulation based on local data is lacking. An agreement of the Ministries of Health for restricting the most toxic pesticides in Central America has potential for progress. The most effective way to reduce risk is to greatly reduce pesticide use. Actions needed include development of multidisciplinary strategies for local studies on health and environmental impact of pesticides; development of sustainable nonchemical agricultural technologies; evaluation of interventions; extending and sharing of expertise within the Region; strengthening of unions and communities; and redefining the role of industry toward development of safer products, with responsible marketing and reliable information. PMID- 11783859 TI - Pests, peasants, and pesticides on the Northern Nicaraguan Pacific Plain. AB - With the aim of exploring possible reasons for dangerous work practices among small-scale farmers in the Pacific plain of Nicaragua, a qualitative study was performed. Four focus groups were involved. The information gathered was analyzed with an emphasis on the farmers' relationships to and perspectives on their crops, the economy, pests, and pesticide hazards. Factors that had been anticipated, such as poverty, inadequacy of protective devices, and environmental factors, were found to lead to dangerous work practices. Cultural factors also affected the farmers' attitudes in ways that favored hazardous work procedures. This finding, which had not been anticipated, has important practical implications. It suggests that, to be effective, education and training courses on occupational health should assure that their design, language, materials, and execution are culturally relevant and appropriate. PMID- 11783860 TI - Pesticide-related illness among migrant farm workers in the United States. AB - Surveillance data show that pesticide-related illness is an important cause of acute morbidity among migrant farm workers in California. A few categories (organophosphates and carbamates, inorganic compounds, and pyrethroids) account for over half of the cases of acute illness. Skin effects dominate the illnesses, although ocular and systemic effects are also common. Exposures occur in various ways (e.g., residues, drift), suggesting that the use of pesticides creates a hazardous work environment for all farm workers. The health care system provided through the Migrant Health Program appears to be underutilized, partially due to barriers to health care access. Pesticide hazards should be ranked based on acute toxicity, chronic toxicity (including reproductive risks), carcinogenic potency, volume applied, and magnitude of worker poisonings. Current surveillance effort should be supported. Risk prevention should focus on substitution of safer compounds, establishing effective protections, and ensuring that these measures are enforced. Improved education for health care providers should be a priority. Growers should be educated about alternative forms of pest control and incentives should be provided to encourage their use. PMID- 11783861 TI - Pesticide exposures among Hmong farmers in Thailand. AB - Highland Hmong farmers in Thailand have abandoned shifting cultivation of subsistence crops and turned to chemical-intensive cultivation of non-narcotic permanent field cash crops. Three highland communities and Hmong in urban Chiang Mai were studied. Most rural study participants applied chemicals, primarily to control insects, weeds, and fungus, by backpack and machine sprays and by hand. Hmong women have less Thai language skill than men and less information concerning hazards of exposure or use of protective clothing. Most Hmong know of the health hazards, but many fail to use adequate protective clothing to prevent exposure. Screening showed 20-69% of 582 Hmong adults with risky or unsafe levels of cholinesterase inhibition, an indicator of exposure to organophosphate and carbamate pesticides. Exposure rates are as high among those who do not actually apply pesticides as among those who do, suggesting exposure by routes in addition to direct contact associated with application. PMID- 11783862 TI - Pesticide-handling practices in agriculture in Tanzania: observational data from 27 coffee and cotton farms. AB - The practices of pesticide handling in agriculture were surveyed in 1991-1993 in Tanzania, to identify hazardous practices and farms where they occurred. The study involved 23 coffee farms with 246 persons exposed to hazardous practices, and four cotton farms with 45 exposed. An observation form addressed locations of important places with respect to pesticide spraying, storage, disposal, and equipment; personal protection; and hygiene. More pesticide formulations were used for coffee compared with cotton and by individual rather than cooperative farms. Coffee farms more often had unlabeled pesticide containers and missing mixing instructions, while cotton pesticides were stored in bedrooms, near food, and near open fires, and pesticide leftovers were often present. Hazardous practices were more pronounced at individual than cooperative farms, with significant differences in pesticide storage areas, as well as unlabeled and non original containers. The study demonstrated the need to train farmers in pesticide safety, strengthen advisory and regulatory services, and extend protection to farm workers' families. PMID- 11783863 TI - The epidemiology of organophosphate poisoning in urban Zimbabwe from 1995 to 2000. AB - The objective of this study was to examine current organophosphate usage in Zimbabwe. A cross-sectional descriptive study was done to determine the trends in admissions for organophosphate poisonings in an urban Zimbabwe hospital from 1995 to 2000. Variables such as sex, age, season, geographic area, and intent were examined. In 183,569 records, 599 cases of organophosphate poisoning were found. Organophosphate poisonings increased by 320% over the six years. The male and female admissions' rates were similar (48% vs 52%); 82% of the patients were less than 31 years old. Suicide was the predominant reason for poisoning (74%). Of admissions of children under the age of 10, 62% were due to accidental ingestion. Mortality from organophosphate poisonings was 8.3% over the six years. Organophosphate poisoning is increasing rapidly. In the background of this alarming trend is the physical, mental, and social state of a Zimbabwean society wrought with hardships. PMID- 11783864 TI - Pesticide health and safety and the work and impact of international agencies: partial successes and major failures. AB - The paper explores aspects of the international role and impact of key agencies in informing regulators and users about pesticides and controlling and preventing pesticide poisoning worldwide. The WHO, IPCS, ILO, World Bank, and related organizations such as ICPS, for instance, all have effects. Particular attention is paid to the IPCS environmental health criteria documents on pesticides. Political and economic influences affect decisions about whether or not to use pesticides, and the risk assessments and data used to assess pesticides. This has significant influence on the selection and use of particular pesticides and hence on both acute and chronic pesticide poisoning cases globally. Progress has been made to correct these covert and damaging influences and imbalances, but more needs to be done to ensure proper accountability and transparency in pesticide health and safety policy and practice. PMID- 11783865 TI - Pesticide use--an inappropriate technology? PMID- 11783866 TI - Endotoxin exposures during potato processing. PMID- 11783867 TI - Mold growth on the Internet. PMID- 11783868 TI - Control of wood dust from random orbital hand sanders. PMID- 11783869 TI - Performance evaluation of on-site colorimetric air sampling techniques. PMID- 11783870 TI - Indoor wet concrete cutting and coring exposure evaluation. PMID- 11783871 TI - Absorption of dimethylacetamide (DMAC) following application of a polymer film to the skin of rabbits. AB - Kapton Film is a polymer with high strength and thermal resistance finding use in a wide variety of applications. In the preparation of this film, the uncured material could contain up to 30% dimethylacetamide (DMAC). Note that the final product Kapton Film has been thermally cured with the DMAC removed. During processing, dermal contact with the film is anticipated, and the possibility exists of DMAC transfer from the uncured film, to and through the skin. In this study, 2 x 2-inch pieces of film were applied to the skin of a group of rabbits and secured in place for a single 4-hour contact time. An amount of liquid DMAC corresponding to the amount contained in the 2-inch square was applied to the skin of a separate group of rabbits for 4 hours. Urine samples were collected over the intervals of application to 4 hours post application (8 hours total) or 4 to 20 hours post application (16 hours). The amount of the urinary metabolite monomethylacetamide (MMAC) was determined analytically in these samples. Urine from 2 untreated rabbits was collected at the same time to serve as controls. The amount of urinary MMAC found in the rabbit rine from animals exposed to uncured Kapton Film at both ollection intervals was similar to the amount seen in the controls (background). Rabbits treated with DMAC liquid had measurable urinary MMAC levels that were approximately 100 times background. It is concluded that, under the conditions of this study, very little, if any, DMAC from the uncured Kapton Film was absorbed through the skin (and excreted in the urine as MMAC). PMID- 11783872 TI - A review of crane safety in the construction industry. AB - The complex, dynamic, and continually changing nature of construction work has been recognized as an important contributor to the high rates of injuries and fatalities in the industry. Cranes are a central component of many construction operations and are associated with a large fraction of construction deaths; in fact, estimates suggest that cranes are involved in up to one-third of all construction and maintenance fatalities. Safety and health professionals serving the construction industry need adequate training and knowledge regarding available crane safety devices and procedures so that they may insure these techniques are effectively utilized during construction operations. This paper reviews available information on crane-related injuries, currently available safety devices, and commonly used crane safety procedures. Recommendations for improved crane injury prevention and future crane safety research are given. PMID- 11783873 TI - Evaluation of biological effects, dosimetric models, and exposure assessment related to ELF electric- and magnetic-field guidelines. AB - Several organizations worldwide have issued guidelines to limit occupational and public exposure to electric and magnetic fields and contact currents in the extremely low frequency range (<3 kilohertz). In this paper, we evaluate relevant developments in biological and health research, computational methods for estimating dosimetric quantities, and exposure assessment, all with an emphasis on the power frequency (60 hertz in North America, 50 hertz in Europe). The aim of each guideline is to prevent acute neural effects of induced electric fields. An evaluation of epidemiological and laboratory studies of neurobiological effects identified peripheral nerve stimulation as the response most suitable for establishing a magnetic-field guideline. Key endpoints that merit further study include reversal of evoked potentials; cardiovascular function, as measured by heart rate and heart rate variability; and sleep patterns. High-resolution computations of induced electric fields and current densities in anatomically correct human models are now achieved with finite-difference methods. The validity and limitations of these models have been demonstrated by computations in regular geometric shapes, using both analytic and numeric computations. Calculated values for average dosimetric quantities are typically within a few percent for the two approaches. However, maximum induced quantities are considerably overestimated by numerical methods, particularly at air interfaces. Overestimates are less pronounced for the upper 99th percentile level of a dosimetric quantity, making this measure a more useful indicator of maximum dose. Neural stimulation thresholds are dependent on the electric field around the excitable cell rather than on the current density, making the former preferable for expression of basic restrictions based on nervous system function. Furthermore, modeling data indicate that the induced electric field is much less strongly influenced by tissue conductivity than is the induced current density. In the electric utility industry, most magnetic-field exposures at or near guideline levels occur in highly nonuniform fields. Two methods are described for simplified estimation of induced quantities in such fields, with each method using as input modeling results for uniform field exposure. These methods have practical value for assessing occupational exposures relative to guideline levels. PMID- 11783874 TI - Characterization of vehicular brake service personnel exposure to airborne asbestos and particulate. AB - Evaluation of fibers and total particulate generated during the servicing of drum brakes on motor vehicles as well as during the resurfacing (arcing) of brake shoes was conducted. Conditions for the studies were based on review of contemporary (approximately 1950-1980) working practices in the industry. This work was conducted in two parts. Phase 1 estimated the release of asbestos fibers and total particulate during brake inspection and replacement of light-duty vehicle rear drum brakes at an auto/truck repair facility. Two distinct work practices were evaluated: One rear wheel from each vehicle was serviced using compressed air to remove dust while the second rear wheel was serviced without compressed air. Area and personal monitoring of fiber levels demonstrated counts (without compressed air) that ranged from 0.05 to 0.2 f/cc. Fiber counts when using compressed air averaged from 0.05 to 0.9 f/cc. Results from real-time aerosol monitoring indicated elevated dust levels for about 15 minutes after blow out. With shop doors open, dust levels increased to 5.0 mg/m3 at blow out and returned to 0.08 mg/m3 within two minutes. When the shop doors were closed, the dust levels reached 13.5 mg/m3 at blow out and decreased to 1.68 mg/m3 within one minute and to background within 14 minutes. The Phase 2 series evaluated the release of fibers and other particulate from are grinding. For operations conducted under conditions simulating a workplace, a mean of 0.19 f/cc +/- 0.16 was determined. Dust levels averaged 0.25 mg/m3 +/- 0.05. Brake service monitoring in these tests demonstrates that asbestos fiber concentrations, considered on a time weighted average basis, should not exceed currently acceptable workplace standards whether or not the worker uses compressed air, nor during the arc grinding process when arcing is conducted in accord with the design of the equipment. PMID- 11783875 TI - Morphological characteristics of asbestos fibers released during grinding and drilling of friction products. AB - There has been considerable interest during the past 30 years regarding the potential for exposure to asbestos fibers generated during asbestos-containing automobile and light-duty truck brake replacement and repair operations. Less attention has been directed to asbestos fiber exposures resulting from servicing of brakes on heavy-duty trucks and other machinery. Potential for the generation of respirable fibers as a result of using a rotary bench grinder and the drilling of asbestos-containing friction pads was investigated to assess the characteristics of the fibers generated from these procedures. The data from the grinding process revealed that this material was either resin matrix or fibers bound to the resin matrix. Fibers generated from the drilling procedure revealed morphology consistent with chrysotile asbestos. In each case, nonfibrous materials remained bound to the fibers released from these processes. These fibers had resin deposits attached. This investigation offers evidence that drilling and grinding of brake pads generates fibers that, for the most part, remain bound to the underlying matrix, suggesting that grinding and drilling may not pose an important source of exposure to respirable asbestos fibers. PMID- 11783876 TI - Use of historical uranium air sampling data to estimate worker exposure potential to airborne radioactive particulate in a uranium processing facility. AB - Historical industrial hygiene monitoring records from a uranium processing plant were collected and analyzed to characterize exposure potential to airborne radioactive particulate. More than 2,100 samples were collected during the period of 1954-1968. The data was organized by job title, plant number, and year of measurement. Laboratory analysis of air samples indicated a wide range of potential exposures to the alpha-emitting particulate. Logarithmic transformation of the data was necessary to approximate Gaussian distributions. Geometric Mean (GM) values were used as the measure of central tendency within years. GM values ranged from 23-49 disintegrations per minute per cubic meter of air sampled (dpm/m3) with the years 1963 and 1964 being significantly higher than other years (ANOVA: p < 0.05). When comparing exposure potential across plants, GM ranged from 20-68 dpm/m3, with plants 5 and 8 being significantly higher than the others (ANOVA: p < 0.05). Exposure potential for specific job titles across the plants varied widely. GM for clerks was the lowest (11 dpm/m3) while furnace operators were the highest (235 dpm/m3). Other job titles with potentially high exposures were chemical operators, forklift operators, machine operators, and furnace operators. This analysis indicates the magnitude and distributions of worker exposure to alpha-emitting airborne particulate. Additional analysis and epidemiologic studies are planned for this facility. PMID- 11783877 TI - Effect of synthesis temperature and doping level on conductivity and structure of poly(3-methyl thiophene). AB - Poly(3-methyl thiophene) was synthesized by oxidative chemical polymerization technique using ferric chloride as the dopant in an inert atmosphere. Samples of different doping levels were prepared and analyzed by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, and direct current (DC) conductivity measurement at room temperature (300 K). Synthesis of the polymer was confirmed by FTIR studies. FTIR spectra showed a shift in the heterocyclic bands in the region of 700-1200 cm(-1) with a decrease in synthesis temperature. It was evident from the scanning electron micrographs that the surface structure of the polymer became denser with an increase in doping level. The measured DC conductivity increased initially up to the doping level of 0.8 M and then this increase tended to slow down. Samples having a doping level of 0.4 M were synthesized at 300, 280, and 270 K while maintaining the other synthesis parameters. The conductivity and yield were found to increase as the temperature of the polymerization decreased. PMID- 11783878 TI - Direct current conductivity studies on poly(3-methyl thiophene). AB - The direct current (DC) conductivity of poly(3-methyl thiophene) was measured in the temperature range of 77-300 K. The observed DC conductivity data were analyzed in the light of Mott's variable range hopping model. Different Mott's parameters such as characteristic temperature (T0), average hopping distance (R), average hopping energy (W), and density of states at the Fermi level (N [E(F)]) were evaluated. By taking the inverse of the coefficient of exponential decay of the localized states involved in the hopping process as 0.5 nm, a realistic value of density of states at the Fermi level (N [E(F)]) was obtained that agrees well with the values reported earlier for other conjugated polymers. PMID- 11783879 TI - Strategies for molecular designing of novel low-band-gap electrically conducting polymers. AB - Molecular designing of low-band-gap electrically conducting polymers continues to be a major challenge of the field of electrically conducting polymers. Such polymers are expected to show not only good intrinsic conductivity but also possibly a good transparency in the visible spectrum for their use as infrared sensors/detectors. Low-band-gap polymers can also be of great interest as new polymeric materials for nonlinear optics. Various routes presently followed to achieve this designing with special reference to the donor-acceptor polymers and important results obtained with this route are briefly reviewed. PMID- 11783880 TI - Contribution of conformational change of polymer structure to electrochemomechanical deformation based on polyaniline. AB - The pH dependencies of electrochemomechanical deformation (ECMD) including the cyclic voltammetry and the expansion ratio in conducting polymers, polyaniline (PANI), and poly(o-methoxyaniline) film were studied to elucidate the mechanisms. It was found that the ECMD is governed by the conformational change of polymer structure as well as the insertion of bulky ions in the manner of comparable magnitude. Expansion ratios >20% in the ECMD were demonstrated for the thickness direction of PANI film. The results suggest that the magnitude of ECMD can be improved by choosing the preparation method of films. PMID- 11783881 TI - Theoretical study of electronic structures and conduction properties of copolymers based on poly(cyclopentadienylene). AB - Various quasi-one-dimensional superlattices (copolymers) (AmBn)x of two novel donor-acceptor polymers PPDCF ([A]x) and PPDCN ([B]x) based on poly(cyclopentadienylene) (PPD) and belonging to the class of type II staggered superlattices were investigated using a negative factor counting method in the tight-binding approximation. Both PPDCF and PPDCN consist of a bicyclopentadienylene unit bridged by an electron-accepting group >C=CF2 in PPDCF and >C=C(CN)2 in PPDCN. The trends in the electronic structures and conduction properties of the copolymers (AmBn)x as a function of the block sizes m and n, arrangement of the units (periodic or random) in the copolymer chain, and length of the copolymer chain are discussed. PMID- 11783882 TI - The role of molecular recognition in charge transport properties of doped polyaniline. AB - Molecular recognition plays a significant role in the counterion-induced processibility, morphological features, and physical properties of doped polyaniline (PANI). The interaction of the counterion and solvent controls the chain conformation and, as a result, the formation of extended and localized electronic states; hence, it holds the key for tuning a wide range of electrical and optical properties of doped PANI. The combined effects of counterion, solvent, and processing conditions tune the metal-insulator transition, temperature dependence of conductivity, magnetoresistance, and so forth in doped PANI. The typical examples are shown in the case of PANI doped by camphor sulfonic acid, 2-acrylamido-2-methyl-1-propane sulfonic acid, and dodecylbenzoyl sulfonic acid. PMID- 11783883 TI - Synthesis and characterization of fluoro-substituted polyaniline. AB - Poly(2-fluoroaniline) was prepared by both chemical and electrochemical polymerization in acidic medium. Characterization of poly(2-fluoroaniline) was accomplished experimentally using ultraviolet-visible, Fourier transform infrared, differential scanning calorimetry, thermal gravimetric analysis, and X ray diffraction techniques, respectively. Scanning electron microscopy studies revealed globular morphology of chemically synthesized poly(2-fluoroaniline). The cyclic voltammetric studies revealed diffusion-controlled phenomenon in electrochemically synthesized poly(2-fluoroaniline). PMID- 11783884 TI - Biochemical evaluation of sulfur and nitrogen assimilation potential of mustard (Brassica juncea L. Czern. & Coss.) under application of slow-release sulfur fertilizer. AB - Pot experiments were conducted to study the efficacy of a slow sulfur-releasing fertilizer, sulfur glass fritz (SGF 1), on growth, photosynthesis, and sulfur, and nitrogen assimilation potentials of brown mustard (Brassicajuncea L. Czern. & Coss. cv. Pusa Jaikisan). Growth as indicated by biomass accumulation slowed down in response to the application of sulfur glass fritz. A similar trend was observed in the case of photosynthesis rate. The activity of two marker enzymes, ATP-sulfurylase and nitrate reductase, showed very low levels of activity, indicating poor assimilation of sulfur and nitrogen by the plant under sulfur glass fritz. It is therefore concluded that the release of sulfur by sulfur glass fritz is too slow and that the initial nonavailability of sulfur to the plants could lead to suboptimization of both sulfur- and nitrogen-assimilating enzymes. These factors may contribute to low rates of photosynthesis and poor growth. PMID- 11783885 TI - Study of vibrational spectra of polyaniline doped with sulfuric acid and phosphoric acid. AB - Vibrational spectra of insulator emeraldine base (EB) form of polyaniline and electrical conductive sulfuric acid- and phosphoric acid-doped emeraldine salts (ES) were studied in the region of 4000-400 cm(-1) at ambient temperature by Fourier transform infrared spectroscopy. Infrared transmittance spectra of EB and ES were investigated to understand the bonding behavior of different organic and inorganic groups present in the polymeric chains and their structural variations on protonation by sulfate or phosphate ion inclusion in the polymer salt network. These studies revealed the para-coupling of deformed disubstituted benzenoid (B) and quinoid (Q) rings with ends capped predominantly by (B4Q1) units. The deformation of B and Q rings was confirmed by the appearance of many weak bands, very weak bands, and satellite structures in strong transmittance peaks of polymeric chain-constituting groups. Protonation takes place at the nitrogen sites of Q rings and forms semiquinone radical ions in ES. The vibrational bands pertaining to B rings, Q rings, B4Q1 units, semiquinone segment, sulfate ions, and phosphate ions were observed and assigned from these measurements. The shift in peak position of some bands with gain or loss in intensity and appearance of some new bands were observed in sulfuric acid- and phosphoric acid-doped ES spectra. These variations are attributed to the formation of new structural groups in ES on protonation and a change in crystalline field by sulfate and phosphate ion doping for crosslinking the polymeric chains. PMID- 11783886 TI - Oncologic applications of biophotonics: prospects and problems. AB - The understanding of various intrinsic photobiophysical processes has prompted researchers to develop different types of biodevices for health care. In the recent past, because of extensive contributions from various groups in the field of biophotonics, several important biomedical applications are emerging in the fields of both diagnostics and therapy. In this brief review, we discuss a few specific applications related to early detection and characterization of premalignant and malignant lesions using optical spectroscopic techniques, namely, fluorescence and Raman, and in management of cancer, the emerging scene of photodynamic therapy. PMID- 11783887 TI - An optical tweezers-based immunosensor for detection of femtomoles-per-liter concentrations of antigens. AB - We used optical tweezers--optical trapping with focused laser beams--to pull microspheres coated with antigens off of an antibody-coated surface. Using this technique, we could quantify the force required to separate antigen to antibody bonds. At very low surface density of antigen, we were able to detect the single antigen to antibody binding. The force required to break the antigen-antibody bonds and pull the microsphere off the surface was shown to increase monotonically with increasing surface density of antigens. Using the force determination as a transducer, we were able to detect concentrations of free antigens in solution as small as 10(-15) mol/L in a competitive binding assay. PMID- 11783888 TI - Soluble substituted poly-p-phenylenes--a new material for application in light emitting diodes: synthesis and characterization. AB - Poly-p-phenylenes have attracted a great deal of attention with respect to their applications in displays, light-emitting devices, and batteries. However, the polymer poly-p-phenylene obtained by the Kovacic method is insoluble and intractable. The present study reports the preparation of soluble poly(p phenylenes) by polymerization of derivatives of benzene in the presence of a specific aromatic nuclei. The resultant copolymer so obtained is soluble in common organic solvents such as chloroform and toluene. Preliminary studies have indicated that the polymer shows orange photoluminescence and electroluminescence when a potential of 7-10 V is applied to the device. PMID- 11783889 TI - Immobilization and stabilization of biomaterials for biosensor applications. AB - Biosensors are finding applications in a variety of analytical fields. A biosensor basically consists of a transducer in conjunction with a biologically active molecule that converts a biochemical signal into a quantifiable electric response. The specificity of the biosensor depends on the selection of the biomaterial. Enzymes, antibodies, DNA, receptors, organelles, microorganisms as well as animal and plant cells or tissues have been used as biologic sensing materials. Advances in biochemistry, molecular biology, and immunochemistry are expected to lead to a rapid expansion in the range of biologic recognition elements to be used in the field of biosensors. Biomaterials that are stable and function even in highly acidic, alkaline, hydrophobic, or oxidizing environments as well as stable to high temperature and immune to toxic substrates in the processing stream will play an important role. Techniques for immobilization of the biomaterials have played a significant role in the biosensor field. Immobilization not only brings about the intimate contact of the biologic catalysts with the transducer, but also helps in the stabilization of the biologic system, thus enhancing its operational and storage stability. A number of techniques have been developed in our laboratory for the immobilization of enzymes, multienzyme systems, cells, and enzyme-cell conjugates. Some of these aspects that are of significance in biosensor applications have been highlighted. PMID- 11783890 TI - Signal amplification by substrate recycling on polyaniline/lactate oxidase/lactate dehydrogenase bienzyme electrodes. AB - The bienzyme electrodes were fabricated by coimmobilization of lactate oxidase (LOD) and lactate dehydrogenase (LDH) onto electrochemically prepared polyaniline (PANI) films. These PANI/LOD/LDH bienzyme electrodes were shown to provide signal amplification by substrate recycling, making it possible to detect L-lactate at lower concentrations (0.1-1 mM). The PANI/LOD/LDH bienzyme electrodes were found to be stable for about 21 d at 4-10 degrees C. PMID- 11783891 TI - Coimmobilization of urease and glutamate dehydrogenase in electrochemically prepared polypyrrole-polyvinyl sulfonate films. AB - Immobilization of urease and glutamate dehydrogenase enzymes in electrochemically prepared polypyrrole-polyvinyl sulfonate films (PPY-PVS) was carried out using physical adsorption and electrochemical entrapment techniques. Detailed studies on optimum pH, Fourier transform infrared spectroscopy, cyclic voltammetry, and scanning electron microscopy of the enzymes in the immobilized state were conducted. The value of the apparent Michaelis-Menten constant was experimentally determined to be 2.5 and 2.7 for physically adsorbed and electrochemically entrapped urease in PPY-PVS films, respectively. PMID- 11783892 TI - Applications of self-assembled monolayers for biomolecular electronics. AB - Preparation and characterization of ordered ultrathin organic films (a few nanometers to several hundred nanometers) has recently attracted considerable attention because of the possibility of controlling order and interactions at the molecular level and has triggered several innovative applications ranging from molecular electronics to tribology. Monomolecular films prepared by self-assembly are attractive for several exciting applications because of the unique possibility of making the selection of different types of terminal functional groups as well as length scales more flexible. The present article discusses various applications of self-assembled monolayers (SAMs) in molecular electronics ranging from biosensors to optoelectronic devices with specific examples. Similarly, SAMs and multilayers of bifunctional molecules on polycrystalline substrates can be effectively used to carry out specific reactions between pendent functionalities and solution or gaseous species to produce new hybrid materials for devices such as molecular diodes. The importance of SAMs in controlling nucleation and growth is also illustrated using biomimetic synthesis of ceramic thin films (biomineralization) of zirconia. PMID- 11783893 TI - Preparation and characterization of poly-N-vinyl carbazole Langmuir-Blodgett films. AB - Langmuir monolayers of poly-N-vinyl carbazole (PNVK) were obtained by dispensing PNVK dissolved in tetrahydrofuran onto an air-water interface. Surface pressure area isotherms of mixed monolayer of the PNVK were studied under different subphase conditions such as temperature and pH of the subphase. It was demonstrated that the monolayer of PNVK remained stable over a temperature range of 10-40 degrees C. The area per molecule of the solid phase was found to be 31 A2. These monolayers were transferred onto indium-tin-oxide-coated glass plates and characterized by spectroscopic and electrochemical techniques. PMID- 11783894 TI - Biomolecular electronics in the twenty-first century. AB - A relentless decrease in the size of silicon-based microelectronics devices is posing problems. The most important among these are limitations imposed by quantum-size effects and instabilities introduced by the effects of thermal fluctuations. These inherent envisaged problems of present-day systems have prompted scientists to look for alternative options. Advancement in the understanding of natural systems such as photosynthetic apparatuses and genetic engineering has enabled attention to be focused on the use of biomolecules. Biomolecules have the advantages of functionality and specificity. The invention of scanning tunneling microscopy and atomic force microscopy has opened up the possibility of addressing and manipulating individual atoms and molecules. Realization of the power of self-assembly principles has opened a novel approach for designing and assembling molecular structures with desired intricate architecture. The utility of molecules such as DNA as a three-dimensional, high density memory element and its capability for molecular computing have been fully recognized but not yet realized. More time and effort are necessary before devices that can transcend existing ones will become easily available. An overview of the current trends that are envisaged to give rich dividends in the next millennium are discussed. PMID- 11783895 TI - Biomaterials for molecular electronics development of optical biosensor for retinol. AB - Molecular electronics involves expertise from several branches of science. Various biomaterials and electronics are involved in the fabrication of such devices. While passive biomaterials are involved in anchoring the active biomolecules, the latter are involved in switching and/or signal transduction. In the present investigation we have used a glass-capillary-based approach to design a biosensor for retinol. The sensing element is retinol-binding protein (RBP). The affinity of retinoic-acid-horseradish peroxidase (conjugate) to RBP is tested using a surface plasmon resonance technique. A simple photomultiplier-tube-based system is exploited to monitor the chemiluminescent signal generated upon reaction of hydrogen peroxide and luminol with the conjugate bound to RBP. The photomultiplier tube is directly coupled to a computer for data logging. PMID- 11783896 TI - Immobilization of lactate dehydrogenase on tetraethylorthosilicate-derived sol gel films for application to lactate biosensor. AB - Tetraethylorthosilicate (TEOS)-derived sol-gel films were utilized for the immobilization of lactate dehydrogenase (LDH) by physical adsorption and sol gel/LDH/sol-gel sandwich configuration. An attempt was made to ascertain the optimum pH and temperature for the immobilized LDH. It was shown that TEOS derived sol-gel films containing physically adsorbed LDH exhibited linearity from 0.5 to 4 mM, whereas those containing LDH in sandwich configuration showed linearity from 0.5 to 3 mM L-lactate. These sol-gel films, immobilized with LDH, were found to be stable for about 4 weeks at 4-10 degrees C. PMID- 11783897 TI - National Symposium on Biomolecular Electronics--Interfacing Physics and Chemistry with Biology. September 16-17, 1999. New Delhi, India. PMID- 11783899 TI - Pigeonpea (Cajanus cajan L.) urease immobilized on glutaraldehyde-activated chitosan beads and its analytical applications. AB - Urease from pigeonpea (Cajanus cajan L.) was covalently linked to crab shell chitosan beads using glutaraldehyde. The optimum immobilization (64% activity) was observed at 4 degrees C, with a protein concentration of 0.24 mg/bead and 3% glutaraldehyde. The immobilized enzyme stored in 0.05 M Tris-acetate buffer, pH 7.3, at 4 degrees C had a t(1/2) of 110 d. There was practically no leaching of enzyme (<3%) from the immobilized beads in 30 d. The immobilized urease was used 10 times at an interval of 24 h between each use with 80% residual activity at the end of the period. The chitosan-immobilized urease showed a significantly higher Michaelis constant (8.3 mM) compared to that of the soluble urease (3.0 mM). Its apparent optimum pH also shifted from 7.3 to 8.5. Immobilized urease showed an optimal temperature of 77 degrees C, compared with 47 degrees C for the soluble urease. Time-dependent kinetics of the thermal denaturation of immobilized urease was studied and found to be monophasic in nature compared to biphasic in nature for soluble enzyme. This immobilized urease was used to analyze blood urea of some of the clinical samples from the clinical pathology laboratories. The results compared favorably with those obtained by the various chemical/biochemical methods employed in the clinical pathology laboratories. A column packed with immobilized urease beads was also prepared in a syringe for the regular and continuous monitoring of serum urea concentrations. PMID- 11783898 TI - Characterization of DNA immobilized on electrochemically prepared conducting polypyrrole-polyvinyl sulfonate films. AB - The article describes the adsorption characteristics of DNA onto electrochemically generated polypyrrole-polyvinyl sulfonate (PPY-PVS) films obtained as a function of pH. Adsorption on PPY doped with an anion proceeds by anion exchange, and since DNA possesses a fixed negative charge owing to PO4-, it favors a very strong binding displacing PVS with favorable energetic interactions. Characterization of adsorbed DNA onto the PPY-PVS films was carried out by ultraviolet-visible, Fourier transform infrared spectroscopy, and cyclic voltammetric studies. PMID- 11783900 TI - Study on photoconductivity of dye-polymer-based solid-state thin film. AB - In this article, we describe a solid-state photoelectrochemical cell for light detection. Safranine-T dye mixed with polyvinyl alcohol (PVA) solution was deposited on a conducting and transparent indium-tin-oxide (ITO)-coated glass that was used as one electrode and another ITO-coated glass as the counterelectrode. A solid polymeric electrolyte consisting of polyethylene oxide ammonium perchlorate-ethylene carbonate and propylene carbonate with suitable weight ratio was prepared and sandwiched between these two ITO-coated glass electrodes, which were separated by a Teflon spacer about 50 microm thick. The cell was biased with a direct current source to make the dye and PVA-coated ITO as the anode and the other ITO as the cathode. On illumination by a tungsten lamp, from the cathode side, the change of photocurrent was measured. The dark current-voltage characteristics and the growth and decay of the photocurrent for steady and pulsed illumination were studied. PMID- 11783901 TI - Copper(II) ion-selective microelectrochemical transistor. AB - A device has been developed for the measurement of copper(II) ions (Cu++) in aqueous medium. The device reported here is an electrochemical transistor that consists of two platinum electrodes separated by 100-microm spacing and bridged with an anodically grown polycarbazole film. The undoped polycarbazole film is observed to be highly selective for the Cu(II) ions. In a completed device, the conductivity of the polycarbazole film changes on addition of Cu (II)ions. This change in conductivity is attributed to the conformational changes in the polymer phase on occupation of the Cu(II) ions, without affecting electron/proton transfer. The device turns on by adding 2.5 x 10(-6) M Cu(II) ions and reaches a saturation region above a concentration of 10(-4) M Cu(II) ions. In this concentration range, the plot of I(D) vs log[Cu(II)] is linear. The selectivity of the device for other metal ions such as Cu(I), Co(II), Fe(II), Fe(III), Zn(II), and Pb(II) is also studied. PMID- 11783902 TI - Semi-solid-state fermentation of Eicchornia crassipes biomass as lignocellulosic biopolymer for cellulase and 3-glucosidase production by cocultivation of Aspergillus niger RK3 and Trichoderma reesei MTCC164. AB - An aquatic weed biomass, Eicchornia crassipes, present in abundance and leading to a threatening level of water pollution was used as substrate for cellulase and beta-glucosidase production using wild-type strain Aspergillus niger RK3 that was isolated from decomposing substrate. Alkali treatment of the biomass (10%) resulted in a 60-66% increase in endoglucanase, exoglucanase, and beta glucosidase production by the A. niger RK3 strain in semi-solid-state fermentation. Similarly, the alkali-treated biomass led to a 45-54% increase in endo- and exoglucanase and a higher (98%) increase in beta-glucosidase production by Trichoderma reesei MTCC164 under similar conditions. However, the cocultivation of A. niger RK3 and T. reesei MTCC164 at a ratio of 3:1 showed a 20 24% increase in endo- and exoglucanase activities and about a 13% increase in the beta-glucosidase activity over the maximum enzymatic activities observed under single culture conditions. Multistep physical (ultraviolet) and chemical (N methyl-N'-nitrosoguanidine, sodium azide, colchicine) mutagenesis of the A. niger RK3 strain resulted in a highly cellulolytic mutant, UNSC-442, having an increase of 136, 138, and 96% in endoglucanase, exoglucanase, and beta-glucosidase, activity, respectively. The cocultivation of mutant UNSC-442 along with T. reesei MTCC164 (at a ratio of 3:1) showed a further 10-11% increase in endo- and exoglucanase activities and a 29% increase in beta-glucosidase activity in semi solid-state fermentation. PMID- 11783903 TI - Electrochemically synthesized polymer of the plant substance embelin (2,5 dihydroxy-3-undecyl-1,4-benzoquinone). AB - Among the possible new materials for microelectronics, quinones have a number of significant advantages. Similarly, polymers with quinone functionality possess biodegradability. Because natural polymers are promising candidates for functional materials for the future, we have initiated studies on the polymers of natural products. In the present study, a natural quinone (a plant substance) extracted from Embelier libes distributed in the Kerala state of India was electrochemically polymerized and its properties were investigated. The redox activity, electrical conductivity, and biodegradability are discussed. PMID- 11783904 TI - Keynote: Functional genomics and DNA chips. PMID- 11783905 TI - Free-energy analysis of enzyme-inhibitor binding: aspartic proteinase-pepstatin complexes. AB - Expeditious in silico determinations of the free energies of binding of a series of inhibitors to an enzyme are of immense practical value in structure-based drug design efforts. Some recent advances in the field of computational chemistry have rendered a rigorous thermodynamic treatment of biologic molecules feasible, starting from a molecular description of the biomolecule, solvent, and salt. Pursuing the goal of developing and making available a software for assessing binding affinities, we present here a computationally rapid, albeit elaborate, methodology to estimate and analyze the molecular thermodynamics of enzyme inhibitor binding with crystal structures as the point of departure. The complexes of aspartic proteinases with seven inhibitors have been adopted for this study. The standard free energy of complexation is considered in terms of a thermodynamic cycle of six distinct steps decomposed into a total of 18 well defined components. The model we employed involves explicit all-atom accounts of the energetics of electrostatic interactions, solvent screening effects, van der Waals components, and cavitation effects of solvation combined with a Debye Huckel treatment of salt effects. The magnitudes and signs of the various components are estimated using the AMBER parm94 force field, generalized Born theory, and solvent accessibility measures. Estimates of translational and rotational entropy losses on complexation as well as corresponding changes in the vibrational and configurational entropy are also included. The calculated standard free energies of binding at this stage are within an order of magnitude of the observed inhibition constants and necessitate further improvements in the computational protocols to enable quantitative predictions. Some areas such as inclusion of structural adaptation effects, incorporation of site-dependent amino acid pKa shifts, consideration of the dynamics of the active site for fine-tuning the methodology are easily envisioned. The present series of studies, nonetheless, creates potentially useful qualitative information for design purposes on what factors favor protein-drug binding. The net binding free energies are a result of several competing contributions with 6 of the 18 terms favoring complexation. The nonelectrostatic contributions (i.e., the net van der Waals interactions) and the differential cavitation effects favor binding. Electrostatic contributions show considerable diversity and turn out to be favorable in a consensus view for the seven aspartic proteinase-inhibitor complexes examined here. Implications of these observations to drug design are discussed. PMID- 11783906 TI - Ultrastructural characteristics of the alveolar phagocytic cells from patients with various forms of chronic bronchitis. AB - Development of chronic bronchitis is accompanied by progressive fibrosis of the bronchial wall. Synchronously, reactivity of phagocytic cells of the alveolar tissue changes. During early (chronic catarrhal bronchitis) and developed (chronic granulating bronchitis, chronic purulent bronchitis, and chronic catarrhal-fibrotic bronchitis) stages in the development of chronic bronchitis, structural signs of activation of phagocytic cells, and an increase of proliferative and metabolic activity of the alveolar macrophages were noted. However, this activation is followed by their depression in chronic fibrotic bronchitis. Data obtained show that in the development of chronic bronchitis, activation followed by depression of cell effectors takes place in the respiratory tissue. PMID- 11783907 TI - Ultrastructural changes and glutathione depletion in the skeletal muscle induced by protein malnutrition. AB - Ultrastructural changes and glutathione level were investigated in the pectoralis muscle of rats fed a low-protein diet. Electron microscopy demonstrated the ultrastructural changes of occasional myofibrils affected with protein deficiency that were characterized with the streaming and/or disruption of the Z-line and disintegration of sarcomeric striation. In the affected sarcomeres, sarcomere length was often elongated and fragmented thick filaments were present together with dense amorphous materials flowing from the damaged Z-line. Glutathione level of muscle in the low-protein diet group (5% casein) was reduced to about one third of that in the control diet group (20% casein). The study suggests that depletion of glutathione by protein malnutrition is responsible for inducing myofibrillar damage through the excess leaking of Ca2+ into the cytosol. PMID- 11783908 TI - Necrobiotic xanthogranuloma without periorbital involvement: an ultrastructural investigation. AB - A case of necrobiotic xanthogranuloma without typical periorbital involvement is described at the ultrastructural level. The patient, a 58-year-old Italian man, presented in 1995 with a brief history of nodulo-papular lesions commencing on the lower limbs, and mild paraproteinemia. During 6 years of follow-up, anemia, neutropenia with marked lymphopenia, and increased ESR were found, while serum cholesterol and triglyceride levels decreased from hyper to hypo values. Systemic diseases, such as diabetes, malignancy, or extracutaneous lesions, often associated with NXG, have not developed. Conventional histology was distinctive for NXG, and immunohistochemistry confirmed that dermal histiocytes were not of Langerhans cell lineage. At ultrastructure, regeneration and degeneration ("regen degen") features were observed in some individual deep dermal histiocytes, which have not been previously documented in the literature. Identification of giant histiocytes showing 'regen-degen'' aspects might prove to be a useful ultrastructural diagnostic marker for NXG. PMID- 11783909 TI - Comparative study of serotonin and bombesin in adenocarcinomas and neuroendocrine tumors of the colon. AB - The aim of this study was to investigate serotonin and bombesin expression in colorectal adenocarcinomas and neuroendocrine colorectal tumors to clarify their role in the progression of colon cancer. The investigation was carried out by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases of colorectal adenocarcinomas were characterized by the presence of amphicrine cells containing endocrine granules and mucus granules. Poorly differentiated adenocarcinomas and liver metastases were poorly granulated compared with highly differentiated tumors. Neuroendocrine tumors nevertheless were characterized by the presence of numerous malignant neuroendocrine cells filled with secretory granules and mucus granules. Bombesin appeared to be located in enterochromaffin-like endocrine cells, which are primarily responsible for the production of serotonin. In colorectal adenocarcinomas there was an inverse correlation between serotonin levels and the degree of differentiation. High serotonin levels characterized colorectal adenocarcinomas with composite phenotype and colorectal neuroendocrine tumors. Increased bombesin expression was correlated with colorectal adenocarcinomas exhibiting poor histological grade and their liver metastases. In conclusion, the findings suggest that high serotonin levels may be an indicator of neuroendocrine differentiation, and bombesin may be a useful marker for colorectal adenocarcinomas with aggressive behavior, PMID- 11783910 TI - Dysembryoplastic neuroectodermal tumor: an ultrastructural study of six cases. AB - Dysembryoplastic neuroectodermal tumor (DNT) is a rare brain neoplasm. Although the tumor pathology is relatively well charactererized, its full clinicopathological spectrum is still discussed, and ultrastructural data on it are very limited. Here, the authors describe detailed ultrastructural pathology of 7 cases of DNT. Each tumor consisted of 3 major elements: neoplastic cells (oligodendroglial-like cells, OLC), elongated processes forming neuropil-like structure, and expanded "mucoid" extracellular space, the latter giving an impression of cellular elements floating within it. Neoplastic cells had round, oval, or elongated nuclei, no discernible nucleoli, and a relatively narrow rim of cytoplasm. Some nuclei were irregular and invaginated, and pseudoinclusions (invaginations of cytoplasm penetrated into toroid-like nuclear formations) were observed. Part of the cytoplasm sequestrated within pseudoinclusions often appeared degenerated with large blebs and electron-lucent vesicles, and some of these contained, in turn, semicircular profiles of unknown significance. Chromatin was clustered below the nuclear membrane. The cytoplasm contained a few mitochondria, round rather than elongated, a few stacks of rough endoplasmic reticulum, and scanty microtubules and clear vesicles. The second element consisted of innumerable cellular processes. Some of these were elongated and formed stacks connected by symmetric or asymetric adhesive plaque junctions. Others had shorter "neck" containing microtubules extending into bulbous extensions. Dense-cored vesicles were occasionally observed, both in the cytoplasm of neoplastic cells and within processes. In one cell, cross-sectioned annulate lamellae were found. In the cytoplasm of a few cells, unusual inclusions reminiscent of ribosome-lamellae resembled "laboratory tubes" with cone-like endings. At higher power, walls of the "tubes" resolved into layered structures composed of several laminae; between these, ribosome-like structures were visible. The authors conclude that OLC exhibit clear-cut characteristics of neuronal cells and not true oligodendocytes. PMID- 11783911 TI - Ultrastructural features of pleomorphic xanthoastrocytoma: a comparative study with glioblastoma multiforme. AB - Eighteen tumors (15 cases) were ultrastructurally examined and compared to 11 examples of glioblastoma multiforme (GBM) [to determine the cellular nature of pleomorphic xanthoastrocytoma (PXA).] PXA, as well as GBM, were principally composed of pleomorphic astrocytes containing numerous intermediate filaments. Lipid droplets, lysosomes, and basal laminas were more numerous and fully developed in PXA, but were not specific to the tumor. Aggregates of secondary lysosomes, light microscopically evident as eosinophilic granular bodies, and ribosome-lamella complexes were exclusively seen in PXA. Also noted in PXA were centrioles, occasional Rosenthal fibers, hemidesmosomes in small number, rudimentary cell junctions, and interstitial calcifications. In addition to astrocytic constituents, 20% of PXA contained cells with neuronal features, as evidenced by the presence of dense-core granules, microtubules, and clear vesicles. In contrast, GBMs consisted solely of astrocytic cells. In the present study, the salient ultrastructural findings of PXA were largely degenerative in nature, including numerous lipid droplets and secondary lysosomes, as well as basal laminas, ribosome-lamella complexes, and occasional neuronal differentiation. The presence of basal lamina does not necessarily imply a histogenetic derivation from subpial astrocytes, in that it is also a common feature of GBM. Given the occurrence of biphenotypic, glioneuronal differentiation in some cases, PXA may be derived from a neuroepithelial stem cell. The authors conclude that PXA is fundamentally an astrocytic tumor, albeit one with a significant tendency to undergo neuronal differentiation. PMID- 11783912 TI - Benign clear cell tumor of the lung. AB - A 49-year-old woman presented with a solitary pulmonary nodule in the right lung. The tumor was well circumscribed and showed a reddish brown cut surface. It showed a diffuse growth pattern of polygonal cells with clear abundant cytoplasm and distinct cell border around thin-walled vascular spaces and sinusoid-type vessels. Based on morphological findings, the patient was diagnosed as having benign clear cell tumor of the lung. Silver impregnation and PAM stains showed fine reticular fibers continuously surrounding the vessels and individual neoplastic clear cells. Strong immunostaining for type IV collagen was observed surrounding all the individual clear cells. A few clear cells were positive for HMB-45 and NCAM 123C3 (CD56). Electron microscopically, clear cells had numerous membrane-bound glycogen granules and a large amount of non-membrane-bound glycogen. The neoplastic cells were surrounded by external lamina and cytoplasmic processes. The neoplastic clear cells showed morphologic features seen in pericytes, melanocytic cells, and neuroendocrine cells. PMID- 11783913 TI - Insulinoma with fibrillar inclusions and acinar cell elements. AB - Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33-year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin. PMID- 11783914 TI - Hepatocellular carcinoma: an update. AB - Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy. PMID- 11783915 TI - Microvillous inclusion disease: report of a case with atypical features. AB - Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease. PMID- 11783916 TI - Chaos and order. PMID- 11783917 TI - Surgical management of severe deformity resulting from posterior tibial tendon dysfunction. AB - A retrospective case study format was used to evaluate the results of surgical treatment of severe deformities due to long-standing tibialis posterior tendon dysfunction. To be included in the study, the peri-talar (talonavicular) subluxation on a weight-bearing AP X-ray should have been at least 75%. This criterion limited the field to patients with long-standing, rigid, severe deformities. Surgical correction was obtained through a two-incision approach, dorsomedial and dorsolateral. Significant shortening of the medial column and extensive removal of adaptive bone formation was necessary to allow reduction of the hind- and midfoot deformity. Stable internal fixation using multiple screws was used to secure the reduction. Eleven patients, 12 feet were evaluated. The patients were evaluated using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Score as well as a questionnaire on footwear and satisfaction rating. The average score improved from 30 points pre-op to 74 points post-op (out of 100). P-value 0.0001. Pain score improved from 11/40 to 33/40. Function improved from 19/50 to 33/50. Alignment improved from 0/10 to 8/10. The radiological parameters showed an average improvement of 31 degrees in the lateral talo-1st metatarsal angle, 11 degrees in the calcaneal pitch, and 35 degrees in the AP talo-1st metatarsal angle. All three parameters were highly significant with P-values of 0.0001. Multiple complications occurred. This included two delayed unions with breakage of screws and partial loss of correction, four wound problems, two sural nerve impairments and three patients requiring hardware removal. Even though it is an extensive procedure with multiple potential complications it still offers a substantial improvement in quality of life. PMID- 11783918 TI - Tibialis posterior insufficiency occurring in a patient without peronei: a mechanical etiology. AB - A patient presented with a painful flatfoot deformity, which developed after the onset of a drop-foot secondary to a herniated lumbar disk. On examination, the only functioning muscles were her gastrocnemius-soleus complex and her intrinsic toe flexors. Her affected foot had taken the classic deformity seen with tibialis posterior dysfunction--a valgus heel, midfoot collapse and an abducted forefoot. Peroneus brevis was not functioning and therefore could not be implicated as part of the etiology of this patient's acquired flatfoot deformity. The mechanism in which the ground reaction force produces the foot deformity in a tibialis posterior insufficient foot will be presented. PMID- 11783919 TI - Case report: positive bone scan findings in grade I posterior tibial tendon dysfunction. PMID- 11783920 TI - Outcome study of hallux valgus surgery--an AOFAS multi-center study. AB - Three hundred and eleven patients have been enrolled in a multi-center prospective study evaluating the outcome of hallux valgus surgery by the members of the American Orthopaedic Foot and Ankle Society. One hundred seventy-nine of these patients have completed six-month follow-up questionnaires, and 195 have completed 12-month questionnaires. The AAOS Lower Limb Outcomes Data Collection Questionnaire and the Foot and Ankle Outcomes Data Collection Questionnaire were used to assess patients' perceptions of their results. Both of these instruments are validated lower extremity instruments. They contain the SF-36 instrument as well as questions relating to lower extremity function. At six- and 12-month follow-up, significant improvement has been noted in the patients' SF-36 physical function scores, role physical scores, and bodily pain scores. Role emotional scores were increased at six months but returned to baseline at 12 months. The scores for physical health and pain and satisfaction with symptoms for the lower extremity have significantly improved. The global foot and ankle score and shoe comfort score from the foot and ankle module have also significantly improved. This outcome study is the first to focus on the patient's perception of results of hallux valgus surgery and demonstrates a significant improvement in pain, function, and satisfaction after bunion surgery performed by members of the American Orthopaedic Foot and Ankle Society. PMID- 11783921 TI - Measurement of first-ray mobility in normal vs. hallux valgus patients. AB - Hypermobility of the first ray is one causative factor in development of hallux valgus and an important factor in the treatment of hallux valgus, but measuring first-ray motion is difficult. There are two known ways of measuring first-ray motion. One is measuring the bony angle on the lateral foot X-ray using a modified Coleman block. The other is using devices. However, neither is suitable for clinical application. We introduce a simple, fast and easy way of measuring first-ray range of motion. Using this method, we compared the first-ray motion between a normal group and a hallux valgus group. Forty normal and 60 hallux valgus patients were included in the measurement. We measured the first-ray range of motion in the following way: with one hand we held the 2nd, 3rd, 4th, and 5th rays at the metatarsal head level with a simple right-angled indicator. With the other hand, we held the first ray at the metatarsal head level using a simple right-angled device, such as a scale. Keeping the other rays fixed, we moved the first ray up and down and recorded the average distance (d) 10 times to reduce intra-measurement differences. We also measured and recorded the first metatarsal length (L) on the anteroposterior foot X-ray film. Finally, we calculated the first-ray range of motion (alpha) using the above data. We also measured the hallux valgus angle and intermetatarsal angle in the hallux valgus patient group. With this method, the average first-ray motion was 10.3 degrees in the normal group and 12.9 degrees in the hallux valgus patient group. If we define 14 degrees, (that is, above the 95th percentile in the normal group) as having hypermobility, 38% of hallux valgus patients had first ray hypermobility. There was no correlation between first-ray hypermobility and either hallux valgus angle or intermetatarsal angle. PMID- 11783922 TI - Mobility of the first tarsometatarsal joint in hallux valgus patients: a radiographic analysis. AB - Hypermobility of the first tarsometatarsal (TMT 1) joint in the sagittal plane plays a role in the etiology and treatment of the hallux valgus complex. However, objective quantification of this mobility is still a problem. We performed a radiographic analysis of TMT 1 mobility in the sagittal plane in 94 hallux valgus patients aged 15 to 65 years. We examined 94 feet with symptomatic hallux valgus deformity requiring operative correction. Excluded were patients with osteoarthritis, inflammatory diseases or previous operations on the foot. The TMT 1 mobility was tested with a clinical test and by radiographic measurement using the modified Coleman block test. The mean mobility of the TMT 1 joint in the sagittal plane in the patient group was 12.9 degrees (SD 4.80). In addition, there was a statistically significant difference between two subgroups: patients with and without clinical TMT 1 hypermobility. No correlation of TMT 1 (hyper)mobility and radiographic second ray hypertrophy was found. This simple method can produce additional information to the clinical TMT 1 hypermobility test in the sagittal plane. PMID- 11783923 TI - The scarf osteotomy for the treatment of hallux valgus deformity: a review of 84 cases. AB - This study reviewed the subjective, clinical and radiological outcome of 71 patients (84 feet) treated by scarf osteotomy for hallux valgus deformity at our institution from 1995 to 1998 with an average follow-up time of 22 months (range, 17 to 48 months). At the time of follow-up, 39% of the patients were very satisfied, 50% were satisfied and 11% were not satisfied. The mean AOFAS score raised significantly from 43 points (14-68) preoperatively to 82 points (39 to 100) at follow-up (p < 0.001). The radiological angles including M1-M2, M1-P1, M1 M5 and DMAA improved significantly (p < 0.001). Among the 16 complications recorded, seven (8%) were minor and nine (11%) required an additional procedure. The scarf osteotomy of the first metatarsal coupled with a lateral soft-tissue release and, in three-quarters of our cases, with a basal closing wedge varisation osteotomy of the first phalanx, resulted in overall high satisfaction rate as well as significant clinical and radiological improvements in our series. Nevertheless, the range of motion of the first MP joint remained low: 30 degrees to 74 degrees in 52 patients (62%) and <30 degrees in four patients (5%). Furthermore, the mobility of the first ray as well as the consequences of the procedure in the sagittal plane need to be assessed more accurately, and this may be achieved by incorporating measurement of the plantar pressures in the forefoot area into the global rating system. PMID- 11783924 TI - Traumatic 'mallet toe' of the hallux: a case report. AB - We describe a case of a traumatic avulsion fracture of the distal phalanx of the hallux. In the upper limb this fracture leads to a "mallet" deformity. Such an injury in the great toe has not been reported previously in the English orthopaedic literature to our knowledge. The injury was treated in a dorsal extension splint for eight weeks. At six months follow-up, a satisfactory clinical outcome was achieved. PMID- 11783925 TI - Early ankle motion after triple bundle technique repair vs. casting for acute Achilles tendon rupture. AB - The purpose of our study is to evaluate the triple bundle technique for acute Achilles tendon rupture repair followed by early (at 14 days) postoperative ankle range of motion compared to nonoperative treatment with delayed ankle range of motion. We retrospectively reviewed 73 patients with an acute Achilles tendon rupture treated with either a plantar flexed cast or surgical repair. We found operative treatment reduces immobilization time, allows safe early return to weight-bearing, and diminishes risk of rerupture compared to nonoperative treatment. However, at an average follow-up of greater than 3.5 years, there was no statistical difference in AOFAS hindfoot scores, strength, or patient satisfaction between the two groups. Significant complications were higher in the nonoperative group manifested by three reruptures (7.7%) vs. one deep wound dehiscence in the operative group (3%). PMID- 11783926 TI - Limited open repair of ruptured Achilles tendons with Bunnel-type sutures. AB - A new method of repairing Achilles tendons, which uses a small medial skin incision with a Bunnel-type suture, was performed on 14 patients, and the clinical results were found satisfying. In order to restore the Achilles tendon to its original length, restore tensile strength in the suture site, and minimize injury to the sural nerve, an operative procedure has been devised which uses a limited open repair with a Bunnel-type suture. We followed 14 patients who had undergone the new procedure for a mean interval of 26 months after the injury. They returned to work in six weeks and to playing sports in 25 weeks. There were no cases of late rerupture nor injuries to the sural nerve. This technique approximated the preinjury length and resting tension of the musculo-tendinous apparatus and minimized sural nerve injury. PMID- 11783927 TI - Highlights of the 17th Annual Summer Meeting of the American Orthopaedic Foot and Ankle Society, San Diego California, July 19-21, 2001. PMID- 11783928 TI - A laser flash photolysis study of curcumin in dioxane-water mixtures. AB - Curcumin [bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] was studied by means of UV-VIS absorption spectroscopy and nanosecond laser flash photolysis in 1,4-dioxane-water mixtures in a series of dioxane-water volume ratios. The transient characteristics were found to be dependent on the amount of water. In pure dioxane the triplet state of the molecule in its enolic form was detected (lambda(max) = 720 nm, tau = 3.2 micros), whereas upon water addition, the diketo form was found to prevail, because of the perturbation of intramolecular H-bonded structure. This led to hydrogen abstraction from dioxane by curcumin triplet state and the formation of the corresponding ketyl radical (lambda(max) = 490 nm, tau approximately 10 micros). Laser flash photolysis measurements, carried out in solvents of different polarity and proticity (benzene, cyclohexane and various alcohols), allowed the transient assignments to be confirmed, supporting our interpretation. PMID- 11783929 TI - Emission of thioflavin T and its off-on control in polymer membranes. AB - The absorption and emission spectral properties of thioflavin T (TFT+) in Nafion (Nf) and cellulose matrices have been studied. Formation of the emittive dimer is observed in both matrices. The monomer TFT+ emission is blueshifted in Nafion membrane (Nf), whereas it is red-shifted in cellulose membrane when compared with the emission in aqueous solution. The dimer emission of TFT+ in the Na+-Nf membrane undergoes off-on switching with acids and alkalis. The TFT+ molecule undergoes protonation in the H+-Nf and the protonated dye is fluorescent. The dimer emission of TFT+ is not observed in the dry H+-Nf membrane because of the protonation of the TFT+ molecule. The diffusion coefficient and the free energy of hydrophobic interaction for the TFT+ molecule in the Nf membrane are calculated. The TFT+ molecule experiences hydrophobic and electrostatic interactions in the Nf matrix, whereas it experiences a polar environment in the cellulose membrane. The 3D emission spectral studies support the formation of the emittive dimer in both Nf and cellulose matrices. PMID- 11783930 TI - Quenching of singlet molecular oxygen (1O2) by azide anion in solvent mixtures. AB - The azide ion is a strong physical quencher of singlet molecular oxygen (1O2) and is frequently employed to show involvement of 1O2 in oxidation processes. Rate constants (k(q)) for the quenching of 1O2 by azide are routinely used as standards to calculate k(q) values for quenching by other substrates. We have measured k(q) for azide in solvent mixtures containing deuterium oxide (D2O), acetonitrile (MeCN), 1,4-dioxane, ethanol (EtOH), propylene carbonate (PC), or ethylene carbonate (EC), mixtures commonly used for many experimental studies. The rate constants were calculated directly from 1O2 phosphorescence lifetimes observed after laser pulse excitation of rose bengal (RB), used to generate 1O2. In aqueous mixtures with MeCN and carbonates, the rate constant increased nonlinearly with increasing volume of organic solvent in the mixtures. k(q) was 4.78 x 10(8) M(-1) s(-1) in D2O and increased to 26.7 x 10(8) and 27.7 x 10(8) M( 1) s(-1) in 96% MeCN and 97.7% EC/PC, respectively. However, in EtOH/D2O mixtures, k(q) decreased with increasing alcohol concentration. This shows that a higher solvent polarity increases the quenching efficiency, which is unexpectedly decreased by the proticity of aqueous and alcohol solvent mixtures. The rate constant values increased with increasing temperature, yielding a quenching activation energy of 11.3 kJ mol(-1) in D2O. Our results show that rate constants in most solvent mixtures cannot be derived reliably from k(q) values measured in pure solvents by using a simple additivity rule. We have measured the rate constants with high accuracy, and they may serve as a reliable reference to calculate unknown k(q) values. PMID- 11783931 TI - Interaction of UVB-absorbing sunscreen ingredients with cutaneous molecules may alter photoimmune protection. AB - Studies of the photoimmunoprotective properties of sunscreens have produced disparate results. In this study in hairless mice, we compared two UVB absorbers, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) and octyl-N-dimethyl-p-aminobenzoate (o PABA), individually formulated in a common base lotion with a sunburn protection factor of 6. We measured their capacity to protect against suppression of the contact hypersensitivity (CHS) induced by three daily exposures of the dorsum to 6x the minimal erythemal/edematous dose (MED) of solar-simulated UV radiation (SSUV), in comparison with base lotion-treated mice exposed to 3 x 1 MED of SSUV. All treatments produced a similar minimal erythema. CHS was equally suppressed in mice irradiated through o-PABA and base lotion, but the suppression was significantly reduced in mice irradiated through 2-EHMC. Neither UVB absorber inhibited the epidermal photoisomerization to the immunosuppressive mediator, cis urocanic acid. However, when mice were treated with exogenous cis-urocanic acid topically on the dorsum, but not when injected subcutaneously on the abdomen, suppression of CHS was observed in o-PABA- and base lotion-treated mice, but not in 2-EHMC-treated mice. Thus, the enhanced immunoprotection in mice irradiated through 2-EHMC apparently resulted from the direct inactivation of epidermal cis urocanic acid by 2-EHMC. We conclude that comparative assessment of photoimmunoprotection by UV absorbers requires SSUV, erythemally matched exposures and consideration of potential interactions with cutaneous molecules. PMID- 11783932 TI - Interannual variability in solar ultraviolet irradiance over decadal time scales at latitude 55 degrees south. AB - Ground-based measurements of solar UV spectral irradiance made from Ushuaia, Argentina at latitude 55 degrees S reveal a large degree of variability among corresponding months of different years over the period from September 1990 through April 1998. The magnitude and wavelength dependence of year-to-year changes in monthly spectral UV-B irradiation are consistent with expectations based on the behavior of column ozone and cloudiness. When combined with satellite measurements of column ozone, a regression model fit to the ground based data set allows estimates of monthly UV-B irradiation over a time frame of two decades, 1978-1998, during several months of the year. Results show a general increase in ground-level irradiation at 305.0 nm from the end of the 1970s to the early 1990s during calendar months from September through December. This is followed by generally smaller irradiances through the middle to late 1990s for all months except November, where the increase continues through the end of the data record. The long-term variability in monthly irradiation over the time period studied is more complicated than can be described by a simple linear trend. PMID- 11783933 TI - Photochemical study of anthracene crystallites by Fourier transform spectroscopic imaging. AB - Fourier transform-based spectroscopic imaging was used for direct, time-resolved, analysis of UV-irradiated anthracene crystallites. Well-resolved fluorescence spectra were obtained at a spatial resolution of 1 microm. The appearance of such photochemical by-products as dianthracene and anthraquinone was monitored throughout the irradiation experiments. Under deaerated conditions, photolysis of anthracene was accompanied by formation of dianthracene. When performed under aerated conditions, however, the spectral data indicated formation of both dianthracene and anthraquinone. Spectral features obtained for the directly monitored photolysis of anthracene are discussed in respect to the structural and compositional modifications in such crystallites. Capabilities of the spectral imaging device for the quantification of the photochemical products of anthracene are discussed. PMID- 11783934 TI - UV doses of American children and adolescents. AB - The ultraviolet (UV) doses of American young adults were never measured, but are needed for assessing UV-related health risks. These doses were calculated using a novel approach. The National Human Activity Pattern Survey recorded the daily minute-by-minute activities of about 2000 young adults (0-19 years) over the course of 2 years to assess their exposure to environmental pollutants. From that survey, only the outdoor daylight data of northern and southern girls and boys were extracted and stratified by season and age to find the time American children (0-5 and 6-12 years) and adolescents (13-19 years) spend outside. They spend about 10% of the day outdoors, but only get about 30% of the available terrestrial UV radiation (on a horizontal plane). American children have about the same percent personal ambients as adults (3.1%), 2.8% for girls and 3.4% for boys. Adolescents have the lowest personal ambients (2.6%), 2.1% for girls and 3.1% for boys. To get their UV doses, their percent ambients are multiplied by the total available terrestrial UV. Excluding vacation, the erythemally weighted UV doses for American children are 25 kJ/m2/year, 23 for girls and 28 for boys. Adolescents get the lowest UV exposure of any group, 21 kJ/m2/year, 18 for girls and 24 for boys. Young adult northern girls get 18 kJ/m2/year and boys get 21 kJ/m2/year, whereas southern girls get 24 kJ/m2/year and boys get 31 kJ/m2/year. The youngest children (0-5 years) get slightly higher summer doses. Thus, we can now assess the UV-related health risks for American children and adolescents. PMID- 11783935 TI - Spectroscopic characterization of bacteriorhodopsin's L-intermediate in 3D crystals cooled to 170 K. AB - Spectra are presented from a single 3D microcrystal of bacteriorhodopsin (bR) cooled to 170 K under various illumination conditions. This set is necessary and sufficient to assign the relevant crystal reference spectra. A spectral decomposition of the difference spectrum obtained following the trapping protocol of Royant et al. (2000) (Nature 406, 645-648) is given, confirming that the low temperature L-intermediate was the species that dominated the structural rearrangements previously reported. Smaller contributions from the K and M spectral intermediates are also quantified. Mechanistic insights derived from the X-ray structures of the early bR intermediates are discussed. PMID- 11783936 TI - Activation of HIV in human skin by ultraviolet B radiation and its inhibition by NFkappaB blocking agents. AB - To determine whether ultraviolet B (UVB) irradiation leads to activation of HIV in human skin, we conducted prospective and controlled studies in two academic medical centers in Texas from July 1995 to April 1999. HIV-positive patients with UV-treatable skin diseases were enrolled at each center, 18 subjects at one and 16 at the other. In one center, specimens from lesional and nonlesional skin biopsies were taken before and after sham- or UVB-irradiation administered in vivo or in vitro. In the other center, UVB phototherapy was administered three times weekly and specimens from skin biopsies were taken before and after 2 weeks (six treatments). Cutaneous HIV load was assessed using reverse transcriptase polymerase chain reaction and reverse transcriptase-polymerase chain reaction in situ hybridization. UVB irradiation led to a 6-10-fold increase in the number of HIV in skin. To ascertain a role for nuclear factor kappa B (NFkappaB) in UVB inducible HIV activation, two types of blockers, NFkappaB oligonucleotide decoy and sodium salicylate, were tested; each inhibited UVB-inducible HIV activation in skin partially. We conclude that UVB irradiation leads to increased numbers of HIV in human skin via processes that include release of cytoplasmic NFkappaB. PMID- 11783937 TI - IL-10 does not play a role in cutaneous Photofrin photodynamic therapy-induced suppression of the contact hypersensitivity response. AB - Photodynamic therapy (PDT) treatment of both malignant and benign skin diseases has proven to be effective, and its use is increasing worldwide. However, preclinical studies using murine models have shown that PDT of the skin inhibits cell-mediated immune reactions, as measured by the suppression of the contact hypersensitivity (CHS) reaction. We have previously demonstrated that PDT enhances IL-10 expression in treated skin, and that the kinetics of induction of IL-10 is similar to the kinetics of suppression of systemic CHS reactions by cutaneous PDT. In the following report we have expanded upon these studies to demonstrate that cutaneous PDT, using Photofrin, induces elevated levels of systemic IL-10 that persist for at least 28 days following treatment. The increase in systemic IL-10 correlates to a prolonged suppression of CHS of at least 28 days following cutaneous PDT. IL-10 has been implicated as the causative agent in the suppression of cell-mediated immune reactions by UVB and transdermal PDT. However, in the studies reported here we demonstrate that the suppression of CHS by cutaneous PDT occurs via an IL-10 independent mechanism, as administration of anti-IL-10 antibodies had no effect on the ability of PDT to induce CHS suppression. These results were further confirmed using IL-10 knockout (KO) mice. Cutaneous PDT of IL-10 KO mice resulted in CHS suppression that was not significantly different from suppression induced in wild-type mice. Thus, it appears as though IL-10 does not play a role in CHS suppression by cutaneous PDT. Suppression of cell-mediated immune reactions by UVB and transdermal PDT is reversible by IL-12, which is critical for the development of these reactions. We show that administration of exogenous IL-12 is also able to reverse CHS suppression induced by cutaneous PDT, suggesting that whereas suppression of cell mediated immune reactions by UVB, transdermal PDT and cutaneous PDT occurs via different mechanisms, a common regulatory point exists. PMID- 11783938 TI - In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy. AB - In this study the endogenous fluorescence signal attributed to reduced nicotinamide adenine dinucleotide (NADH) has been measured in response to photodynamic therapy (PDT)-induced damage. Measurements on cells in vitro have shown that NADH fluorescence decreased relative to that of controls after treatment with a toxic dose of PDT, as measured within 30 min after treatment. Similarly, assays of cell viability indicated that mitochondrial function was reduced immediately after treatment in proportion to the dose delivered, and the proportion of this dose response did not degrade further over 24 h. Measurements in vivo were used to monitor the fluorescence emission spectrum and the excited state lifetime of NADH in PDT-treated tissue. The NADH signal was defined as the ratio of the integrated fluorescence intensity of the 450 +/- 25 nm emission band relative to the fluorescence intensity integrated over the entire 400-600 nm range of collection. Measurements in murine muscle tissue indicated a 22% reduction in the fluorescence signal immediately after treatment with verteporfin based PDT, using a dose of 2 mg/kg injected 15 min before a 48 J/cm2 light dose at 690 nm. Control animals without photosensitizer injection had no significant change in the fluorescence signal from laser irradiation at the same doses. This signal was monotonically correlated to the deposited dose used here and could provide a direct dosimetric measure of PDT-induced cellular death in the tissue being treated. PMID- 11783939 TI - The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin. AB - The skin of nude mice was exposed to erythemogenic doses of UV radiation, which resulted in erythema with edema. An ointment containing 5-aminolevulinic acid (ALA) was topically applied on mouse and human skin. Differences in the kinetics of protoporphyrin accumulation were investigated in normal and UV-exposed skin. At 24 and 48 h after UV exposure, skin produced significantly less protoporphyrin IX (PpIX) than skin unexposed to UV. Human skin on body sites frequently exposed to solar radiation (the lower arm) also produced less PpIX than skin exposed more rarely to the sun (the upper arm). It is concluded that UV radiation introduces persisting changes in the skin, relevant to its capability of producing PpIX from ALA. The observed differences in ALA-induced PpIX fluorescence may be the result of altered penetration of ALA through the stratum corneum or altered metabolizing ability of normal and UV-exposed skin (or both). PMID- 11783940 TI - Additional evidence for the cyclic GMP signaling pathway resulting in the photophobic behavior of Stentor coeruleus. AB - We report that exo- and endogenous guanosine 3',5'-cyclic monophosphate (cGMP) specifically influenced the photophobic response. In behavioral experiments the slowly hydrolyzable and membrane-permeable analogs of cGMP (8-bromo-cGMP [Br cGMP] and N6,2'-o-dibutyryl-cGMP) dramatically prolonged the time for ciliary stop response and decreased the duration of ciliary reversal in a dose-dependent manner. When analogs of adenosine 3',5'-cyclic monophosphate (cAMP) (8-bromo-cAMP or N6,2'-o-dibutyryl-cAMP) were used, no essential effects were detected on the kinetics of the photophobic response. Both nonspecific cyclic nucleotide phosphodiesterase (PDE) activity inhibitors (3-isobutyl-1-methylxanthine [IBMX] and 1,3-dimethylxanthine [theophylline]) and the highly specific cGMP-PDE activity inhibitor 1,4-dihydro-5-[2-propoxyphenyl]-7H-1,2,3-triazolo[4,5 d]pyrimidine-7-one (zaprinast) mimicked the effects of cGMP analogs. Treatment of cells with an inhibitor of guanylate cyclase activity (6-anilino-5,8 quinolinedione [LY 83583]) exerted an effect opposite to that of cGMP analogs and PDE activity inhibitors. The positive physiological effect of LY 83583 was significantly diminished in ciliates that were treated simultaneously with Br cGMP. In an assay of cell cyclic nucleotide content, the exposure of dark-adapted Stentor to light evoked a transient decrease in the basal level of intracellular cGMP. Alterations in internal cGMP levels were more distinct when the intensity of applied illumination was increased. In the presence of IBMX or theophylline the basal content of cGMP was markedly enhanced, and the photoinduced changes in cGMP level were less pronounced. In this paper the possible whole molecular mechanism by which the ciliary orientation in Stentor is controlled by light is presented. PMID- 11783941 TI - The nature of the delocalized cations in azulenic bacteriorhodopsin analogs. AB - Depending on the size and shape of their azulenic chromophores, azulenic bacteriorhodopsin (bR) pigment analogs can exist as either an initial pigment P1, a more red-shifted final pigment P2 or an equilibrium mixture of both. The absorption spectra of red-shifted bR analogs exhibit characteristic narrow-band shapes similar to charge fully delocalized cyanine-like dyes. Therefore, all such red-shifted pigments are believed to be highly delocalized, bond-equalized carbocations. We have determined structural requirements that facilitate their formation. To describe fully the red-shift potentials of these retinal analogs, we have introduced a new parameter-percent red-shift (PRS). A large PRS value not only reflects the extent of red-shift, but is also suggestive of extensive delocalization of the positive charge. Relevance of these findings in consideration of the possibility of forming stable O-intermediates is presented. The postulated resonance hybrid-like structures for different cations of the positively charged protonated Schiff base chromophores are in fact structurally distinct species, equilibrating in response to local perturbations within the supramolecular protein environment. PMID- 11783942 TI - A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin. AB - We have examined transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin for mutations that might modulate the iron burden of individuals harboring the common mutant hemochromatosis HFE genotype C282Y/C282Y or cause hemochromatosis independent of mutations in the HFE gene. In a group of white, Asian, and African American normal and iron-overloaded individuals, the coding and flanking regions of these genes were completely sequenced. Numerous coding region and promoter polymorphisms were detected. These were further examined for association with differences in iron accumulation as measured by plasma transferrin saturation and ferritin levels, but no such association could be documented. PMID- 11783943 TI - Nucleotide variation regulates the level of enhancement by hypersensitive site 2 of the beta-globin locus control region. AB - The beta-globin locus control region hypersensitive site 2 (HS2) enhancer possesses a unique property for stimulating high-level globin gene expression. Although the deletion of cis-acting motifs influences the level of enhancement conferred by HS2, there is controversy on whether polymorphism of the same elements contributes to variation of the fetal hemoglobin (HbF) level among patients with sickle cell anemia. We analyzed reporter gene activity of constructs containing variant HS2 enhancers derived from beta(S) chromosomes to directly test the effect of polymorphism on enhancer activity. Constructs containing four enhancer variants linked to an identical gamma-globin promoter showed markedly different levels of reporter gene activity. Juxtaposition of HS2 derived from the Asian and Senegal chromosomes, which are associated with similarly high levels of HbF, to cognate sequence extending to -1500 of the (G)gamma globin gene showed significantly different levels of reporter gene activity. Our findings indicate that nucleotide variation regulates the level of enhancement conferred by HS2; however, the reporter activities showed no correlation with the level of Hb F associated with the common beta(S) chromosomes. PMID- 11783944 TI - Modulation of intracellular Ca(2+) concentration by vitamin B12 in rat thymocytes. AB - We have studied several novel effects of vitamin B12 (cyanocobalamin) on cellular Ca(2+) homeostasis in rat thymocytes. We determined the effect of various concentrations of vitamin B12 on intracellular Ca(2+) concentration ([Ca(2+)]i) and parameters of Ca(2+)in signaling using the fluorescent dye Fura-2. The basal [Ca(2+)]i in Ca(2+)-containing media was 115 +/- 5 nM but in vitamin B12 (10 nM) treated thymocytes [Ca(2+)]i was decreased to 60 +/- 15 nM (mean +/- SEM) during the first 5 min. The decline in [Ca(2+)]i was accompanied by an increase in the endoplasmic reticulum Ca(2+) store, presumably as a result of Ca-ATPase activation. At the same time 100 nM-10 mM B12 induced the accumulation of Ca(2+) in mitochondria. Somewhat higher concentrations of B12 (1-10 microM) had no effect on [Ca(2+)]i. A further increase in B12 concentration with range from 50 microM to 1 mM caused a dose-dependent elevation of [Ca(2+)]i from the basal level (115 +/- 5 nM) up to 200 +/- 50 nM in thymocytes, and this elevation was partially blocked in Ca(2+)-free media. This high concentration of vitamin B12 caused a gradual decrease of endoplasmic reticulum Ca(2+) stores by means of Ca ATPase inhibition. The B12-induced increase in [Ca(2+)]i was not observed after depletion of intracellular Ca(2+) stores, induced by addition of 2',5'-di(tert butyl)-1,4-benzohydroquinone (BHQ), an inhibitor of endoplasmic reticulum Ca (2+) ATPase, concanavalin A, or arachidonic acid. These studies show that vitamin B12 regulates [Ca(2+)]i via several different mechanisms at different B12 concentrations. Participation of G proteins and calmodulin activity in B12 mediated [Ca(2+)]i increase is discussed. PMID- 11783946 TI - The bigger the C-value, the larger the cell: genome size and red blood cell size in vertebrates. AB - Vertebrate genome sizes vary roughly 350-fold and correlate with a variety of cellular and organismal parameters. Most notable among these is the relationship between genome size ("C-value") and red blood cell (RBC) size, which can be identified within and among each of the five vertebrate classes. This relationship, in turn, leads to important associations between genome size and features such as metabolic rate (at least in homeotherms). The present article describes the correlation between genome size and RBC size in vertebrates and discusses some of the cytological, physiological, and evolutionary implications of this relationship. PMID- 11783945 TI - PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells. AB - PBK/TOPK is a recently cloned serine/threonine kinase which is phosphorylated during mitosis. Earlier work indicated that this kinase is upregulated in a Burkitt's lymphoma cell line (GA-10). To determine whether PBK/TOPK is upregulated in other mitotically active neoplastic cell lines and tissues, Northern analysis was performed on a panel of malignant cell lines and on clinical samples from patients with leukemia or lymphoma. While PBK/TOPK mRNA was not detectable in normal peripheral blood cells and was weakly expressed in hyperplastic tonsillar B-cells, significantly higher levels of mRNA were detected in 8 Burkitt's lymphoma cell lines, 10 other neoplastic cell lines, and 2 clinical samples-one derived from a patient with ALL and a second derived from a patient with relapsed myeloma. In addition, Northern analysis of fetal tissues showed upregulated expression of PBK/TOPK in fetal kidney, lung, spleen, brain, and testis. These data suggest that PBK/TOPK expression is increased in highly proliferative malignant cells and during normal fetal development. PMID- 11783947 TI - Kinetic mechanism of DIDS binding to band 3 (AE1) in human erythrocyte membranes. AB - Stilbenedisulfonates (S) are used widely in cell biology as competitive inhibitors of anion exchange, but the mechanism of competition is not resolved. Resolution requires understanding the detailed steps in the reaction of stilbenedisulfonates with various anion-exchange proteins. Studies on the reversible binding of DBDS (4,4'-dibenzamido-2,2'-stilbenedisulfonate) and H2DIDS (4,4'-diisothiocyanatodihydro-2,2'-stilbenedisulfonate) to erythrocyte band 3 (B) have shown biphasic kinetic time courses at 25 degrees C. Yet, results for the reversible binding of DIDS (4,4'-diisothiocyanato-2,2'-stilbenedisulfonate) are controversial. One recent report has shown monophasic kinetics, in experiments performed at 0 degrees C, and at a single, very low concentration of DIDS (0.1 microM). Studies are presented which attempt to reconcile these recent findings with the other kinetic data in the literature. We measure the kinetics of DIDS reversible binding to band 3, over a wide DIDS concentration range. In addition, the time course for DIDS binding to band 3 at 0 degrees C is compared with that at 25 degrees C. The results show biphasic binding kinetics at both 0 and 25 degrees C, and they are consistent with expectations for a two-step binding mechanism (S + B <--> SB <--> SB*). Furthermore, computer-assisted model simulation studies reveal that monophasic DIDS binding kinetics are generated by a two-step mechanism, when calculations are performed at 0.1 microM DIDS and 0 degrees C. Under these conditions the initial binding step in the two-step reaction becomes rate limiting. We conclude that the two-step binding mechanism best describes stilbenedisulfonate binding to band 3 and that the observation of monophasic kinetics at low concentrations of DIDS, while valid, is not mechanistically discriminating, since both one-step and two-step mechanisms can yield the same result. PMID- 11783948 TI - Downeast anemia (dea), a new mouse model of severe nonspherocytic hemolytic anemia caused by hexokinase (HK(1)) deficiency. AB - A new spontaneous mutation in the A/J inbred mouse strain, downeast anemia (dea), causes severe hemolytic anemia with extensive tissue iron deposition and marked reticulocytosis. The anemia is present at birth and persists throughout life. The defect is inherited as an autosomal recessive and is transferable through bone marrow stem cells. The red cell morphology is consistent with a nonspherocytic hemolytic anemia, suggestive of a red cell enzymopathy. In linkage analysis, dea is nonrecombinant with the hexokinase-1 gene (Hk1) on mouse Chromosome 10. Expression of Hk1 is markedly decreased in dea erythroid tissues, and the transcript produced is larger than normal. Hexokinase enzyme activity is significantly decreased in dea tissues, including red cells, spleen, and kidney. Southern blot analyses revealed approximately 5.5 kb of additional sequence in the 5' portion of the dea Hk1 gene, which was identified by direct sequencing as an early transposon (ETn) insertion in intron 4. ETn insertions disrupt genes in several mouse models by a variety of mechanisms, including aberrant splicing of ETn sequences into the mRNA. We conclude that the primary gene defect in the dea mutation is in Hk1 and that dea is a model of generalized hexokinase deficiency, the first such model identified to date. PMID- 11783949 TI - In utero fetal liver cell transplantation without toxic irradiation alleviates lysosomal storage in mice with mucopolysaccharidosis type VII. AB - Lysosomal storage diseases, such as Mucopolysaccharidosis type VII (MPS VII), cause progressive loss of mobility and intellect and result in early death. Treatment of progressive diseases must occur before the blood-brain barrier closes. In MPS VII mice, normal donor hematopoietic cells secrete the missing enzyme beta-glucuronidase (GUSB) that reverses disease manifestations. Correction of lysosomal storage is limited to the visceral organs unless transplantation is preceded by high-dose irradiation. We hypothesize that irradiation opens the blood-brain barrier allowing passage of corrective cells. Here we transplanted genetically myeloablated MPS VII fetuses to determine whether earlier treatment without toxic irradiation is systemically corrective. Cells with a selective advantage in utero were identified. Donor fetal liver cells (FLC), a substitute for difficult to obtain murine cord blood cells, were increased 10-fold in the host peripheral blood over equivalent numbers of adult marrow cells injected simultaneously and were stable long term in both primary and secondary hosts. GUSB- MPS VII fetuses injected with GUSB+ FLC were assessed longitudinally after birth. Donor FLC replaced host stem cell descendants, prolonged life dramatically, and reduced bone dysplasia and lysosomal storage in all tissues long term. GUSB, donor leptomeningeal cells, and microglia were present in the brain at 11 months postinjection. Lysosomal storage in cortical neurons and glia, although not completely corrected, was reduced. We conclude that in utero intervention without toxic pretreatment in this model reduces the storage disease long term and improves the length and quality of life despite exerting only minor effects on the brain. PMID- 11783950 TI - A region upstream of the human delta-globin gene shows a stage-specific interaction with globin promoters in erythroid cell lines. AB - We previously showed that the 651-bp DNA fragment, located 3 kb upstream from the human delta-globin gene (fragment F5), is able to inhibit adult, not fetal, globin promoter in mouse erythroleukemia cell lines (MEL) expressing adult globin genes. Here we show in transient analysis that fragment F5 has a strong inhibitory effect on fetal gamma-globin promoter in human erythroleukemia cell lines (HEL) expressing fetal globin genes. Since the beta-promoter constructs were poorly expressed in fetal cells, new plasmids containing an HPFH promoter (Ggamma(-175), T to C), which is strongly expressed in both fetal and adult cell lines, were made. Here we report that fragment F5 in HEL cells has a strong inhibitory effect on wild-type gamma-promoter only; no effect was evident on gamma(-175)-promoter in either MEL or HEL cell lines. Altogether these results show a stage-specific interaction between fragment F5 and globin promoters during development. We also report the presence of several bindings for erythroid GATA family factors by electrophoretic mobility shift assay, using nuclear extracts from erythroid cell lines. PMID- 11783951 TI - Mutation prevalence among 51 unrelated Spanish patients with Gaucher disease: identification of 11 novel mutations. AB - Gaucher disease is an autosomal recessive disorder caused by mutations in the lysosomal beta-glucocerebrosidase (GBA) gene. Gaucher disease is a very heterogeneous entity due to the large number of different mutations existing in the GBA gene, resulting in a defective protein whose impaired activity is the cause of the disease. We present a mutation analysis of the GBA gene in 51 unrelated Spanish Gaucher disease patients together with clinical findings. Two common mutations, c.1226A>G (N370S) and c.1448T>C (L444P), were determined by restriction enzyme digestion after PCR amplification of genomic DNA. The remaining alleles were screened by amplifying the entire GBA gene followed by nested PCR and SSCP analysis under four different conditions. The c.1226A>G (N370S) and c.1448T>C (L444P) mutations were common, accounting for 56 alleles (55%) and 16 alleles (15%), respectively. In addition, 25 different mutations were found, 11 of which are described here for the first time: c.(-203)A>G, c.160G>A (V15M), c.256C>T (R47X), c.445-2a>g (IVS4-2a>g), c.485T>C (M123T), c.914C>T (P266L), c.953delT, c.1124T>C (L336P), c.1207A>C (S364R), c.1214delG,C, and c.1510delT,C,T (465delSer). Two mutations, S364R and P266L, were associated with neuronopathic forms of Gaucher disease: S364R mutation in heterozygosity with the L444P mutation and the P266L mutation in a homozygous state. Two type 1 patients were found to be carriers of two mutations in the same allele (genotypes [N370S] + [E326K + N188S] and [N370S] + [IVS4-2a>g+c.(-203)A>G]). This study allowed us to identify 100% of mutant alleles, and therefore we conclude that the method used to screen for mutations in the GBA gene is very reliable and there is a broad spectrum of mutations in the GBA gene in the Spanish population. PMID- 11783952 TI - A rare case of a patient heterozygous for the hemochromatosis mutation C282Y and homozygous for H63D. AB - We describe a woman, found as part of a screening study on cases of elevated transferrin saturation values in France, who was heterozygous for the C282Y mutation and at the same time homozygous for the H63D mutation in the HFE gene. Our description includes two other recently described patients presenting the symmetrical genotypic statement (homozygous for the C282Y mutation and heterozygous for the H63D mutation). The C282Y and H63D mutations in the "cis" phase may thus account for some very rare cases. PMID- 11783953 TI - Monitoring of MRP-like activity in human erythrocytes: inhibitory effect of isoflavones. AB - A method to fluorometrically monitor efflux of 2',7'-bis-(carboxypropyl)-5(6) carboxyfluorescein (BCPCF) from human erythrocytes was developed. Genistein, daidzein, sophoraisoflavone A, and licoisoflavone A induced 50% inhibition (IC(50)) of BCPCF efflux at 15-70 microM. The IC(50) value of the most efficient isoflavone, licoisoflavone A (15-25 microM), was comparable to that of indomethacin (approximately 10 microM) and markedly lower than for probenecid (100-200 microM), both known MRP1 inhibitors. Our results indicate that the human erythrocyte is a useful cell model in screening potential MRP inhibitors, that BCPCF is a good substrate for MRP, and that some isoflavones at low concentrations inhibit MRP-mediated efflux. PMID- 11783954 TI - Mechanistic basis for site-site interactions in inhibitor and substrate binding to band 3 (AE1): evidence distinguishing allosteric from electrostatic effects. AB - Kinetic studies suggest that stilbenedisulfonates inhibit erythrocyte anion exchange by competing with substrate anions for binding to band 3 (AE1). Such competition seems to involve site-site interactions between distinct inhibitor and substrate binding sites. The molecular basis for site-site interactions could be allosteric or electrostatic. In this paper, inhibitor binding kinetic studies are reviewed, and 35Cl(-) NMR line-broadening experiments are presented, both of which seem to rule out an electrostatic hypothesis. The results are consistent with an allosteric site-site interaction mechanism in the binding of stilbenedisulfonate and substrate anions to band 3. PMID- 11783955 TI - The fundamental prevalence of chronic myeloid leukemia-generating clonogenic cells in the light of the neutrality theory of evolution. AB - A variety of normal human tissues have been reported to harbor small cell populations carrying potentially oncogenic gene rearrangements. This backdrop of mutant cells may be present in the majority of healthy individuals and is apparently weakly selected against. This may provide empirical support for the concept of global neutrality, or near-neutrality (very weak selection), of many somatic mutations. Many healthy individuals, as well as patients with chronic myeloid leukemia, manifest the BCR-ABL fusion gene in blood cells. The presumed neutrality of the BCR-ABL rearrangement-carrying pluripotential hematopoietic stem cells and the relative uniformity of the incidence rate of CML worldwide were used to estimate the extent of the background of BCR-ABL-positive stem cells and the numerical size of the human pluripotential hematopoietic stem cell pool. Three different approaches (molecular-epidemiological, statistical, and population genetical) were employed. Each resulted in very similar estimates of the size of the stem cells carrying the BCR-ABL allele fusions (1.4 x 10(4) cells) and the size of the total human stem cell pool (1.6 x 10(9) cells per individual). The implication of these estimates in the context of the hierarchical nature of the stem cell pool is also considered. The presumptive smaller-sized population of CD34(-) stem cells could not be characterized by any of the approaches used as a "founding" population, representing an ultimate source of all hematopoietic progenitors, or as a subset of stem cells comprising a deeper "kinetic" segment of the total (10(9)-sized) stem cell compartment. PMID- 11783956 TI - Low glucose-6-phosphate dehydrogenase enzyme activity level at the time of hemolysis in a male neonate with the African type of deficiency. AB - Glucose-6-phosphate dehydrogenase (G6PD) levels are not usually drawn in the evaluation of black neonates with hyperbilirubinemia because of the oft-stated opinion that the levels may be normal at the time of hemolysis and thus will be misleading. In fact, this opinion is not applicable to newborns as many studies have shown that deficiency in the conjugating ability of the liver, not hemolysis, is the main cause of neonatal jaundice associated with G6PD deficiency. We present a case report of a neonate with brisk hemolysis and hyperbilirubinemia in whom the G6PD level was abnormally low at the time of the hemolytic episode. DNA analysis showed him to have the A-(202A,376G) variant and, as well, the UGT1A1 promoter repeat polymorphism associated with Gilbert's disease. This case, as well as a review of the literature, indicates that enzyme levels are not normal in patients with G6PD A- who are undergoing hemolysis. PMID- 11783957 TI - Muscle-derived stem cells: characterization and potential for cell-mediated therapy. AB - Skeletal muscle may represent a convenient source of stem cells for cell-mediated gene therapy and tissue-engineering applications. A population of cells isolated from skeletal muscle exhibits both multipotentiality and self-renewal capabilities. Satellite cells, referred to by many as muscle stem cells, are myogenic precursors that are capable of regenerating muscle and demonstrating self-renewal properties; however, they are considered to be committed to the myogenic lineage. Muscle-derived stem cells, which may represent a predecessor of the satellite cell, are considered to be distinct. This article considers the evidence for the existence of muscle-derived stem cells as well as their potential embryonic origin. Comparison of muscle-derived stem cells to bone marrow and hematopoietic-derived stem cells illustrates similarities and distinctions among these various stem cells. Hematopoietic stem cell research provides lessons for the isolation of a defined phenotype as well as for the expansion of the stem cells in vitro. Recent investigations highlighting the potential of stem cell transplantation for the treatment of muscular dystrophies are discussed. PMID- 11783959 TI - Human ERMAP: an erythroid adhesion/receptor transmembrane protein. AB - A human cDNA and gene encoding for human ERMAP, a putative erythroid transmembrane adhesion/receptor protein, is reported. The predicted protein is made up of 475 amino acids and shares high homology with the murine ERMAP (73% identity and 14% conservative changes). Human Ermap is highly expressed in erythroid tissues and the protein localizes to the plasma membrane, particularly in sites of cell contact, and "cytoplasmic bodies." The extracellular segment contains one IgV fold that shares high homology with the butyrophilin family of milk proteins, autoantigens, and avian blood group antigens. In the intracellular region, there is a conserved B30.2 domain that is encoded by a single exon and is highly homologous with a similar domain in a diverse group of proteins, including butyrophilin, pyrin, and MID 1. The human Ermap gene is composed of 11 exons spanning 19 kb on chromosome 1p34. PMID- 11783958 TI - Physical and physiological plasticity of hematopoietic stem cells. AB - Stem cells from a variety of tissues have recently been shown to be capable of differentiating into cells characteristic of a separate tissue, apparently in response to microenvironmental signals. This is hierarchical plasticity. We have shown that both human and murine neurosphere cells with potential for differentiating into neurons, oligodendrocytes, and astrocytes can produce hematopoietic stem cells when engrafted into fetal sheep or murine day 3.5 blastocysts, respectively. We have also demonstrated an alternative form of stem cell plasticity: functional plasticity at different points in cell cycle transit and at different phases of a circadian rhythm. We have shown that long-term engraftment varies reversibly as primitive murine stem cells (lineage-negative rhodamine(low) Hoechst(low)) transit the cell cycle under stimulation by interleukin-3 (IL-3), IL-6, IL-11, and steel factor, with engraftment being defective in late S/early G2. Engraftment also varies markedly with circadian time. Presumptive mechanisms for these phenotypic shifts include alteration in adhesion protein expression with consequent changes in marrow homing. Most recently, we have also demonstrated that stem cell differentiation varies markedly with cell cycle transit. There are other features of the hematopoietic stem cell which suggest that it is a highly plastic cell with the ability to rapidly change its membrane phenotype, while exhibiting extraordinary directed motility. These data suggest that cell cycle and circadian plasticity should be considered additional major features of the hematopoietic stem cell phenotype. PMID- 11783960 TI - New insights into the origin of the Gaucher disease-causing mutation N370S: extended haplotype analysis using the 5GC3.2, 5470 G/A, and ITG6.2 polymorphisms. AB - Gaucher disease is a lysosomal storage disorder inherited as an autosomal recessive trait. It is highly prevalent among Ashkenazi Jews but also present in other populations. Mutations in the glucocerebrosidase gene are the main cause of the disorder. One of these gene defects, N370S, is the most prevalent disease allele in the Ashkenazi Jewish patient population and also frequent in others, such as the Spanish and Portuguese Gaucher disease populations. Previous results based on haplotype analysis support the hypothesis of a single origin for this mutation. We have extended the haplotype analysis to include three newly described polymorphisms, 5GC3.2, ITG6.2 (very close to the gene), and 5470 G/A (in intron 7 of the GBA gene) in a sample of Spanish and Ashkenazi Jewish patients. The results confirm the single origin of the mutation in these two populations. The 5470A allele is only found in N370S chromosomes and was believed to be limited to the Portuguese population. Here we describe that it is also present with a similar frequency in Spain. Moreover, most of the 5470A alleles are found within particular haplotypes, which have some differences from the common N370S haplotype. PMID- 11783961 TI - Blindness and severe visual impairment in facial fractures: an 11 year review. AB - We present an 11 year review of facial fractures treated in the Australian Craniofacial Unit and the Department of Plastic and Reconstructive Surgery at the Royal Adelaide Hospital, specifically looking at those fractures in adults that resulted in blindness or severe visual impairment. During the period 1989-2000, a total of 2516 patients with facial fractures were treated operatively. From our facial-fracture database, 317 patients were identified as having an ophthalmological complication on presentation. Of these, 19 had severe visual impairment or blindness. The exact fracture pattern and craniofacial disruption score were recorded for each of these 19 cases using the Cooter-David facial fracture scoring system. Laterally directed forces are implied as major causative factors in these injuries. Recommendations are made based on these findings. PMID- 11783962 TI - V-Y advancement flap and composite graft for alar-groove reconstruction. AB - A one-stage procedure combining a V-Y advancement flap with a composite graft for the reconstruction of alar-lobule and alar-groove defects is described. After tumour resection, a V-Y flap is advanced and retained at the level of the piriform margin to fill the dead space. To provide vascular support to the composite graft and to recreate the alar groove the advancing edge of the flap is de-epithelialised. In the same stage the composite graft is harvested and placed into the alar defect. A series of 12 patients underwent this procedure, with good results. PMID- 11783963 TI - Rehabilitation of the paralysed or lax lower eyelid using a graft of conchal cartilage. AB - Excessive laxity of the tarso-ligamentous sling of the lower eyelid may be caused by inadequate muscular support (resulting from injury to the muscle, facial palsy or senile degeneration) or prolonged mechanical distension (exophthalmia). Numerous techniques have been devised for functional reconstruction of the distended lower eyelid, based upon the principle that restoring the lower eyelid to its anatomical position will improve lacrimal transit andre-establish its natural protective function. We now use an autologous conchal cartilage graft to treat the distended or atonic lower eyelid. We review our results in a retrospective study of 20 patients, and aim to identify the indications for this procedure and to evaluate its advantages and disadvantages relative to other existing methods. All of our patients reported functional improvement after the operation in terms of decreased dry-eye symptoms, less epiphora and a decline in keratitis and conjunctivitis. All patients also reported a visible cosmetic improvement postoperatively. The major drawback of this operation is the partial loss of the visual field when looking down, due to the limited lowering of the lower eyelid. The stability of our results compares favourably with that achieved using other currently available techniques. We conclude that autologous conchal cartilage grafting is an effective procedure for improving both the function and the appearance of the atonic lower eyelid. PMID- 11783964 TI - One hundred cases of endoscopic brow lift. AB - The senior author's experience of using the endoscopic brow lift for rejuvenation of the upper third of the face is presented. One hundred patients underwent endoscopic brow elevation. In 98 cases this was done in combination with other aesthetic procedures. Patient follow-up ranged from 4 months to 53 months (mean: 17 months). No major complications were experienced, although a patient questionnaire identified a number of troublesome but transient minor complications. Levels of patient satisfaction were found to be high. The continuing evolution of this technique is reviewed, particularly relating to methods of brow fixation. PMID- 11783965 TI - Hypoglossal-facial crossover in facial-nerve palsy: pure end-to-sideanastomosis technique. AB - Hypoglossal-facial crossover is the most popular method of reconstructing the facial nerve in facial palsy resulting from proximal facial-nerve injury near the brainstem. Conventional hypoglossal-facial crossover involves performing a partial hypoglossal-nerve section or incision and an interpositional nerve graft to bridge the gap between the two nerves, which sometimes results in hemiglossal atrophy and its sequelae. Furthermore, the nerve graft may delay recovery and make facial reanimation weak. To solve these problems, we attempted to perform 'pure end-to-side anastomosis' (without section of the hypoglossal nerve) between the hypoglossal and facial nerves in four patients with facial palsy. In two patients (group I) a sural-nerve graft was used to bridge the gap between the two nerves. In the other two patients (group II) the intratemporal facial nerve was mobilised to the neck and one tension-free end-to-side anastomosis was performed. Facial symmetry and tone at rest were restored in all cases. Facial reanimation was achieved in group II after 8 months. Despite the small number of cases, we believe that the technique of hypoglossal-facial crossover with 'pure end-to-side anastomosis' and mobilisation of the intratemporal facial nerve can decrease donor-nerve morbidity in facial-nerve rehabilitation. PMID- 11783966 TI - An analysis of the strengths and weaknesses of endoscopic and radiological investigations of velopharyngeal incompetence based on a 20 year experience of simultaneous recording. AB - The simultaneous recording of nasopharyngoscopy and video fluoroscopy allows a comparison to be made of their reliability under various circumstances. While the monocular view and the number of optical fallacies make measurement from endoscopy impossible, radiological views can also be shown to be fallacious, and all measurements should be treated with caution. However, through clinical observation the variability of the final dimensions of tissues raised to treat velopharyngeal incompetence can be roughly gauged. Indeed, the need for more accurate measurement awaits the arrival of a predictable procedure to allow fine tuning of surgery. Simultaneous recording has permitted improved clarity of interpretation and accuracy of measurement in some cases. The chief gain from investigations over the past 30 years has been in the considerably increased understanding of the range of normal and pathological morphology that must be taken into account in surgical treatment. PMID- 11783967 TI - The anatomical and neurophysiological basis of the sensate free TRAM and DIEP flaps. AB - Recent developments in autogenous breast reconstruction using the rectus abdominis myocutaneous free flap include attempts to reinnervate the flap tissue. We have carried out anatomical studies to determine the nature of abdominal-wall cutaneous innervation, with particular emphasis on the harvesting of sensate flaps. Dissections were performed on four embalmed and 12 fresh human cadavers (32 sides). The lowest five intercostal nerve trunks were identified and traced to the lateral border of the rectus sheath. A detailed dissection of the intramuscular course of the nerves and associated vasculature was performed. The relationship of the nerves to the vascular perforators used for rectus abdominis myocutaneous flaps was determined visually, and confirmed histologically. In contrast to previous studies, we show that nerves supplying cutaneous sensation can travel with both medial and lateral vascular perforators. In order to confirm clinically useful innervation, the abdominal flap skin of five patients undergoing TRAM flap reconstruction was stimulated electrically, and sensory recordings were made directly from the related intercostal nerve just prior to flap harvest. These studies represent, to our knowledge, the first clinical application of neurophysiological techniques to outline the perforator neurosomes of flaps based on the deep inferior epigastric vascular axis. We provide the first comprehensive study of abdominal-wall innervation with regard to sensate free-flap harvest. Our dissections show complex patterns of abdominal skin innervation that have not been previously described. The implications for sensate free TRAM and DIEP flap reconstructions, as well as the potential for more accurate inclusion of innervated flap skin, are discussed. PMID- 11783968 TI - UK guidelines for the management of cutaneous melanoma. AB - These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the UK, they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery. PMID- 11783969 TI - Vascular endothelial growth factor gene therapy in ischaemic rat skin flaps. AB - Gene therapy with the complementary DNA (cDNA) of the angiogenic cytokine vascular endothelial growth factor (VEGF) has emerged as a promising strategy in the treatment of myocardial and lower-limb ischaemia. The objective of this study was to determine whether these principles could be applied to a recognised model of skin-flap ischaemia. Plasmid vectors including the cDNA of green fluorescent protein (GFP) and one of three VEGF isoforms (A165, B167 or B186) were constructed, and their base sequences confirmed. GFP expression was used as a marker of successful in vitro transfection of human endothelial cells with each plasmid. The plasmids were then administered subcutaneously to rat abdominal skin flaps surgically rendered ischaemic, and the percentage of viable tissue was assessed at 1 week. Angiograms of the flaps and histological preparations of flap tissue were assessed for evidence of angiogenesis. The survival of flaps treated with VEGF A165 or B167 cDNA was significantly greater than that of controls (P < 0.05). The survival of flaps treated with VEGF B186 cDNA was greater than that of controls, but statistical significance was not reached. Angiograms and microvessel density counts failed to produce evidence of angiogenesis. With improved delivery strategies, VEGF may have a role in the management of surgical ischaemia. PMID- 11783970 TI - Accelerating flap maturation by vascular endothelium growth factorin a rat tube flap model. AB - The effect of exogenous vascular endothelium growth factor (VEGF) on the survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part I, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle was divided after an interval of 3, 4, 5 or 7 days, and the survival area of each distal skin paddle was measured 5 days after the pedicle was divided. The percentages of survival were 0, 24.9%, 89.9% and 100%, respectively. In part II, tube flaps were created in 20 rats. In the experimental group, 2 ml of VEGF (50 microg ml(-1)) was injected into the recipient bed during tube flap creation in each rat. In the control group, 2 ml of saline was given. The tubed pedicle was divided 4 days after creation. The mean survival area of the distal skin paddle in the group treated with VEGF was 7.32 +/- 1.36 cm(2) (80.91%) at 5 days after pedicle division, which was of statistical significance when compared with the survival in the control group of 2.70 +/- 1.89 cm(2) (27.9%). The histology showed angiogenesis at the skin paddle-recipient bed interface following VEGF injection. These results demonstrate that the subcutaneous administration of VEGF into the recipient bed of the tube flap transfer can induce angiogenes is at the junction between the donor and the recipient bed, and improve skin paddle survival with early pedicle division. PMID- 11783971 TI - The double-barrelled end-to-end microvascular anastomosis. AB - We describe a simple alternative method of microvascular anastomosis to the internal jugular vein, which is useful when part of the internal jugular vein has been sacrificed and the free flap has two draining venae commitantes. In our hands, this method has proven to be quick, efficient and successful. PMID- 11783972 TI - Redefinition of the helical rim in cauliflower-ear surgery. AB - Cauliflower ear is a serious deformity of the auricle induced by single or repeated injury to the external ear. Few papers deal with surgical techniques for correcting this deformity. We describe the use of ipsilateral excess cartilage to restore the helical rim. PMID- 11783973 TI - The 6p deletion syndrome: a new orofacial clefting syndrome and its implications for antenatal screening. AB - Foetal genetic screening has become the centre of the ethical debate surrounding the screening of foetuses for chromosomal defects to help create 'eugenic' children with either perceived advantageous characteristics or traits that could be used to medically aid unhealthy siblings. This report highlights the problems facing the medical establishment by citing, by way of example, a case of a genetic abnormality producing a clefting syndrome. The 6p deletion syndrome was first described almost 20 years ago, and the evidence is mounting for its inclusion as an orofacial clefting syndrome. This case report includes a description of the syndrome, the method used for detecting chromosomal aberrations and a comparison with other reports of the syndrome published to date. However, by pursuing a genetic-testing policy at our unit to detect new abnormalities or to help substantiate previously reported abnormalities, the way could be left open for its subsequent abuse by parents and corporations alike, so having implications not only for the individual but also for the unit performing the test. A brief synopsis is therefore also provided regarding the current circumstances of foetal screening in the UK. PMID- 11783974 TI - Orbital reconstruction following sino-nasal mucormycosis. AB - We discuss the reconstruction of an orbit destroyed by an invasive fungal infection. Sino-nasal mucormycosis is usually associated with a poor prognosis, and occurs almost exclusively in immunocompromised patients. Serial imaging leading to repeated radical debridement, along with intravenous amphotericin, helped the patient to recover from this serious disease. A well-vascularised galeal frontalis-pericranial flap from the mid-forehead region was used to reconstruct the orbital defect. PMID- 11783976 TI - Intratendinous rupture of flexor digitorum profundus caused by non-specific synovitis. AB - Closed ruptures of flexor tendons in the hands of patients without rheumatoid arthritis are rare. We report a case of closed rupture of the flexor digitorum profundus of the middle finger in zone II, secondary to acute florid synovitis forming a tumour-like mass. No similar case has been reported to our knowledge. The management of this unexpected finding at surgical exploration is discussed. PMID- 11783975 TI - Solitary fibrous tumour of the face: a rare case report. AB - Solitary fibrous tumour is a rare mesenchymal neoplasm that most commonly involves the pleura. The diagnosis of solitary fibrous tumour is primarily histological. It consists of histological and positive immunohistochemical findings of CD-34 and vimentin. Recently, solitary fibrous tumour has been reported to occur in extrapleural soft tissues, such as the orbit, nasal cavity, abdominal cavity, parotid gland, scalp and neck. In an extensive review of the literature, we found no reports of solitary fibrous tumour arising in the facial soft tissue, other than in the parotid gland. This rare location of an uncommon lesion can lead to a confusing diagnosis. We report a case of solitary fibrous tumour originating in the temporal region of the face, and call for awareness of this tumour among plastic surgeons. PMID- 11783977 TI - A sacrococcygeal extraspinal ependymoma in a 67-year-old man: a case report and review of the literature. AB - Extraspinal ependymomas are extremely uncommon tumours of glial origin. They occur predominantly in children and adolescents. We report a case of a subcutaneous extraspinal ependymoma in a 67-year-old man. This was excised, and the defect reconstructed with a V-Y advancement flap. PMID- 11783978 TI - Ischial pressure sore reconstruction using an inferior gluteal artery perforator (IGAP) flap. AB - Perforator-flap technique has revolutionised the practice of free tissue transfer with the goal of muscle sparing for function and strength. These concepts are being widely explored for breast reconstruction. The field of pressure-sore reconstruction presents a new application for this technique, preserving muscle for function in ambulatory patients and for future reconstruction in paraplegic patients. Just as the superior gluteal artery perforator flap holds promise for sacral and trochanteric reconstruction, the inferior gluteal artery perforator flap may provide a muscle-sparing alternative for ischial reconstruction. A case report of the successful use of an inferior gluteal artery perforator flap for ischial pressure-sore reconstruction is described, including the surgical technique employed for flap harvest, and 2 year's follow-up. PMID- 11783979 TI - Porcine dermal collagen graft in abdominal-wall reconstruction. AB - We describe the use of a porcine dermal collagen graft in the reconstruction of a large abdominal-wall defect in a woman. The graft was not rejected and, after 1 year, was not associated with incisional hernia. This graft may become an alternative to synthetic-mesh and flap reconstructions because, despite being of a similar tensile strength, it promotes less adhesion, is incorporated into the host tissue and is less prone to infection. PMID- 11783980 TI - The accuracy of preoperative chordee evaluation in hypospadias. PMID- 11783981 TI - Venous augmentation of the free TRAM flap. PMID- 11783982 TI - Sternomastoid muscle flap for parotidectomy: the pros and cons. PMID- 11783983 TI - 'Salute splint': a useful alternative. PMID- 11783984 TI - Continuous infusion of muscle relaxant facilitates closure of the TRAM-flap donor site. PMID- 11783985 TI - Emergency treatment of accidental infusion leakage in the newborn. PMID- 11783986 TI - Surgery without sutures: circular excision in the treatment of small cutaneous lesions. PMID- 11783987 TI - Imaginary figures of childhood: an under-used resource in plastic surgery? PMID- 11783989 TI - Activins as regulators of branching morphogenesis. AB - Development of glandular organs such as the kidney, lung, and prostate involves the process of branching morphogenesis. The developing organ begins as an epithelial bud that invades the surrounding mesenchyme, projecting dividing epithelial cords or tubes away from the site of initiation. This is a tightly regulated process that requires complex epithelial-mesenchymal interactions, resulting in a three-dimensional treelike structure. We propose that activins are key growth and differentiation factors during this process. The purpose of this review is to examine the direct, indirect, and correlative lines of evidence to support this hypothesis. The expression of activins is reviewed together with the effect of activins and follistatins in the development of branched organs. We demonstrate that activin has both negative and positive effects on cell growth during branching morphogenesis, highlighting the complex nature of activin in the regulation of proliferation and differentiation. We propose potential mechanisms for the way in which activins modify branching and address the issue of whether activin is a regulator of branching morphogenesis. PMID- 11783991 TI - A reciprocal relationship between cutaneous nerves and repairing skin wounds in the developing chick embryo. AB - Various studies have suggested that the rate of adult skin healing may be in some way dependent on signals emanating from cutaneous nerves. Further, it appears that adult wounds become hyperinnervated by sensory nerves during the process of healing. In order to investigate this reciprocal relationship further, we have used a simple embryonic model to look at the effect of wounds on nerves, and conversely, the effect of nerves on wounds. We find that wounds made to the dorsum of the chick wing bud, at a stage prior to normal innervation (at E4), or soon after the normal establishment of cutaneous innervation (at E7), subtly alter the pattern of branching by perturbing developmental guidance cues, but do not cause hyperinnervation, whereas wounding at E14 does cause hyperinnervation. By creating chicks with nerveless wings, we show that from E7, wound healing in the absence of nerves is significantly impaired. These observations suggest that, from the earliest stages of skin innervation, the presence of nerves is beneficial to the healing process, but that, in contrast to neonatal and adult tissues, wound healing in the embryo and early foetus does not trigger hyperinnervation. PMID- 11783990 TI - Molecular integration of inductive and mesoderm-intrinsic inputs governs even skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors. AB - Individual somatic muscles and heart progenitors are specified at defined positions within the mesodermal layer of Drosophila. The expression of the homeobox gene even-skipped (eve) identifies one specific subset of cells in the dorsal mesoderm, which give rise to particular pericardial cells and dorsal body wall muscles. Genetic analysis has shown that the induction of eve in these cells involves the combined activities of genes encoding mesoderm-intrinsic factors, such as Tinman (Tin), and spatially restricted signaling activities that are largely derived from the ectoderm, particularly those encoded by wingless (wg) and decapentaplegic (dpp). Here we show that a Dpp-activated Smad protein, phosphorylated Mad, is colocalized in eve-expressing cells during an extended developmental period. We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo. This enhancer also contains a number of binding sites for the Wg-effector Pangolin (Pan/Lef-1), which are required for full levels of enhancer activity. However, we find that their main function is to prevent ectopic enhancer activity in the dorsal mesoderm. This suggests that, in the absence of Wg signaling, Pan binding serves to abrogate the synergistic activities of Smads and Tin in eve activation while, in cells that receive Wg signals, Pan is converted into a coactivator that promotes eve induction. Together, these data show that the eve enhancer integrates several regulatory pathways via the combinatorial binding of the mesoderm-intrinsic regulator Tin and the effectors of the Dpp and Wg signals. PMID- 11783992 TI - Multiple inductive signals are involved in the development of the ctenophore Mnemiopsis leidyi. AB - Ctenophores possess eight longitudinally arrayed rows of comb plate cilia. Previous intracellular cell lineage analysis has shown that these comb rows are derived from two embryonic lineages, both daughters of the four e(1) micromeres (e(11) and e(12)) and a single daughter of the four m(1) micromeres (the m(12) micromeres). Although isolated e(1) micromeres will spontaneously generate comb plates, cell deletion experiments have shown that no comb plates appear during embryogenesis following the removal of e(1) descendents. Thus, the m(1) lineage requires the inductive interaction of the e(1) lineage to contribute to comb plate formation. Here we show that, although m(12) cells are normally the only m(1) derivatives to contribute to comb plate formation, m(11) cells are capable of generating comb plates in the absence m(12) cells. The reason that m(11) cells do not normally make comb rows may be attributable either to their more remote location relative to critical signaling centers (e.g., e(1) descendants) or to inhibitory signals that may be provided by other nearby cells such as sister cells m(12). In addition, we show that the signals provided by the e(1) lineage are not sufficient for m(1)-derived comb plate formation. Signals provided by endomesodermal progeny of either the E or the M lineages (the 3E or 2M macromeres) are also required. PMID- 11783993 TI - Peripheral glia direct axon guidance across the CNS/PNS transition zone. AB - CNS glia have integral roles in directing axon migration of both vertebrates and insects. In contrast, very little is known about the roles of PNS glia in axonal pathfinding. In vertebrates and Drosophila, anatomical evidence shows that peripheral glia prefigure the transition zones through which axons migrate into and out of the CNS. Therefore, peripheral glia could guide axons at the transition zone. We used the Drosophila model system to test this hypothesis by ablating peripheral glia early in embryonic neurodevelopment via targeted overexpression of cell death genes grim and ced-3. The effects of peripheral glial loss on sensory and motor neuron development were analyzed. Motor axons initially exit the CNS in abnormal patterns in the absence of peripheral glia. However, they must use other cues within the periphery to find their correct target muscles since early pathfinding errors are largely overcome. When peripheral glia are lost, sensory axons show disrupted migration as they travel centrally. This is not a result of motor neuron defects, as determined by motor/sensory double-labeling experiments. We conclude that peripheral glia prefigure the CNS/PNS transition zone and guide axons as they traverse this region. PMID- 11783994 TI - Hemangioblast commitment in the avian allantois: cellular and molecular aspects. AB - We recently identified the allantois as a site producing hemopoietic and endothelial cells capable of colonizing the bone marrow of an engrafted host. Here, we report a detailed investigation of some early cytological and molecular processes occurring in the allantoic bud, which are probably involved in the production of angioblasts and hemopoietic cells. We show that the allantois undergoes a program characterized by the prominent expression of several "hemangioblastic" genes in the mesoderm accompanied by other gene patterns in the associated endoderm. VEGF-R2, at least from stage HH17 onward, is expressed and is shortly followed by transcription factors GATA-2, SCL/tal-1, and GATA-1. Blood island-like structures differentiate that contain both CD45(+) cells and cells accumulating hemoglobin; these structures look exactly like blood islands in the yolk sac. This hemopoietic process takes place before the establishment of a vascular network connecting the allantois to the embryo. As far as the endoderm is concerned, GATA-3 mRNA is found in the region where allantois will differentiate before the posterior instestinal portal becomes anatomically distinct. Shortly before the bud grows out, GATA-2 was expressed in the endoderm and, at the same time, the hemangioblastic program became initiated in the mesoderm. GATA-3 is detected at least until E8 and GATA-2 until E3 the latest stage examined for this factor. Using in vitro cultures, we show that allantoic buds, dissected out before the establishment of circulation between the bud and the rest of the embryo, produced erythrocytes of the definitive lineage. Moreover, using heterospecific grafts between chick and quail embryos, we demonstrate that the allantoic vascular network develops from intrinsic progenitors. Taken together, these results extend our earlier findings about the commitment of mesoderm to the endothelial and hemopoietic lineages in the allantois. The detection of a prominent GATA-3 expression restricted to the endoderm of the preallantoic region and allantoic bud, followed by that of GATA 2, is an interesting and novel information, in the context of organ formation and endoderm specification in the emergence of hemopoietic cells. PMID- 11783995 TI - Temporary disruption of the retinal basal lamina and its effect on retinal histogenesis. AB - An experimental paradigm was devised to remove the retinal basal lamina for defined periods of development: the basal lamina was dissolved by injecting collagenase into the vitreous of embryonic chick eyes, and its regeneration was induced by a chase with mouse laminin-1 and alpha2-macroglobulin. The laminin-1 was essential in reconstituting a new basal lamina and could not be replaced by laminin-2 or collagen IV, whereas the macroglobulin served as a collagenase inhibitor that did not directly contribute to basal lamina regeneration. The regeneration occurred within 6 h after the laminin-1 chase by forming a morphologically complete basal lamina that included all known basal lamina proteins from chick embryos, such as laminin-1, nidogen-1, collagens IV and XVIII, perlecan, and agrin. The temporary absence of the basal lamina had dramatic effects on retinal histogenesis, such as an irreversible retraction of the endfeet of the neuroepithelial cells from the vitreal surface of the retina, the formation of a disorganized ganglion cell layer with an increase in ganglion cells by 30%, and the appearance of multiple retinal ectopias. Finally, basal lamina regeneration was associated with aberrant axons failing to correctly enter the optic nerve. The present data demonstrate that a transient disruption of the basal lamina leads to dramatic and probably irreversible aberrations in the histogenesis in the developing central nervous system. PMID- 11783996 TI - The outflow tract of the heart is recruited from a novel heart-forming field. AB - As classically described, the precardiac mesoderm of the paired heart-forming fields migrate and fuse anteriomedially in the ventral midline to form the first segment of the straight heart tube. This segment ultimately forms the right trabeculated ventricle. Additional segments are added to the caudal end of the first in a sequential fashion from the posteriolateral heart-forming field mesoderm. In this study we report that the final major heart segment, which forms the cardiac outflow tract, does not follow this pattern of embryonic development. The cardiac outlet, consisting of the conus and truncus, does not derive from the paired heart-forming fields, but originates separately from a previously unrecognized source of mesoderm located anterior to the initial primitive heart tube segment. Fate-mapping results show that cells labeled in the mesoderm surrounding the aortic sac and anterior to the primitive right ventricle are incorporated into both the conus and the truncus. Conversely, if cells are labeled in the existing right ventricle no incorporation into the cardiac outlet is observed. Tissue explants microdissected from this anterior mesoderm region are capable of forming beating cardiac muscle in vitro when cocultured with explants of the primitive right ventricle. These findings establish the presence of another heart-forming field. This anterior heart-forming field (AHF) consists of mesoderm surrounding the aortic sac immediately anterior to the existing heart tube. This new concept of the heart outlet's embryonic origin provides a new basis for explaining a variety of gene-expression patterns and cardiac defects described in both transgenic animals and human congenital heart disease. PMID- 11783997 TI - The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionally regulated by the notch signaling pathway. AB - We have identified a gene encoding a novel protein that is transcriptionally regulated by the Notch signaling pathway in mammals. This gene, named Nrarp (for Notch-regulated ankyrin-repeat protein), encodes a 114 amino acid protein that has a unique amino-terminus and a carboxy-terminal domain containing two ankyrin repeat motifs. A Xenopus homolog of the Nrarp gene was previously identified in a large-scale in situ hybridization screen of randomly isolated cDNA clones. We demonstrate that in T-cell and myoblast cell lines expression of the Nrarp gene is induced by the intracellular domain of the Notch1 protein, and that this induction is mediated by a CBF1/Su(H)/Lag-1 (CSL)-dependent pathway. During mouse embryogenesis, the Nrarp gene is expressed in several tissues in which cellular differentiation is regulated by the Notch signaling pathway. Expression of the Nrarp gene is downregulated in Notch1 null mutant mouse embryos, indicating that expression of the Nrarp gene is regulated by the Notch pathway in vivo. Thus, Nrarp transcript levels are regulated by the level of Notch1 signaling in both cultured cell lines and mouse embryos. During somitogenesis, the Nrarp gene is expressed in a pattern that suggests that Nrarp expression may play a role in the formation of somites, and Nrarp expression in the paraxial mesoderm is altered in several Notch pathway mutants that exhibit defects in somite formation. These observations demonstrate that the Nrarp gene is an evolutionarily conserved transcriptional target of the Notch signaling pathway. PMID- 11783998 TI - Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. AB - Interactions between ingrowing nerve fibers and their target tissues form the basis for functional connectivity with the central nervous system. Studies of the developing dental pulp innervation by nerve fibers from the trigeminal ganglion is an excellent example of nerve-target tissue interactions and will allow specific questions regarding development of the dental pulp nerve system to be addressed. Dental pulp cells (DPC) produce an array of neurotrophic factors during development, suggesting that these proteins might be involved in supporting trigeminal nerve fibers that innervate the dental pulp. We have established an in vitro culture system to study the interactions between the dental pulp cells and trigeminal neurons. We show that dental pulp cells produce several neurotrophic factors in culture. When DPC are cocultured with trigeminal neurons, they promote survival and a specific and elaborate neurite outgrowth pattern from trigeminal neurons, whereas skin fibroblasts do not provide a similar support. In addition, we show that dental pulp tissue becomes innervated when transplanted ectopically into the anterior chamber of the eye in rats, and upregulates the catecholaminergic nerve fiber density of the irises. Interestingly, grafting the dental pulp tissue into hemisected spinal cord increases the number of surviving motoneurons, indicating a functional bioactivity of the dental pulp-derived neurotrophic factors in vivo by rescuing motoneurons. Based on these findings, we propose that dental pulp-derived neurotrophic factors play an important role in orchestrating the dental pulp innervation. PMID- 11783999 TI - The Gli2 transcription factor is required for normal mouse mammary gland development. AB - The hedgehog signal transduction network performs critical roles in mediating cell-cell interactions during embryogenesis and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer, and other tumors. The Gli gene family (Gli1, Gli2, and Gli3) encodes zinc finger transcription factors that act as mediators of hedgehog signal transduction. In this study, we investigate the role of Gli2 in mammary gland development. Mammary expression of Gli2 is developmentally regulated in a tissue compartment-specific manner. Expression is exclusively stromal during virgin stages of development but becomes both epithelial and stromal during pregnancy and lactation. The null phenotype with respect to both ductal and alveolar development was examined by transplantation rescue of embryonic mammary glands into physiologically normal host females. Glands derived from both wild type and null embryo donors showed ductal outgrowths that developed to equivalent extents in virgin hosts. However, in null transplants, ducts were frequently distended or irregularly shaped and showed a range of histological alterations similar to micropapillary ductal hyperplasias in the human breast. Alveolar development during pregnancy was not overtly affected by loss of Gli2 function. Ductal defects were not observed when homozygous null epithelium was transplanted into a wild type stromal background, indicating that Gli2 function is required primarily in the stroma for proper ductal development. DeltaGli2 heterozygotes also demonstrated an elevated frequency and severity of focal ductal dysplasia relative to that of wild type littermate- and age-matched control animals. PMID- 11784000 TI - Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster. AB - Modulation of reactive oxygen species (ROS) plays a key role in signal transduction pathways. Selenoproteins act controlling the redox balance of the cell. We have studied how the alteration of the redox balance caused by patufet (selD(ptuf)), a null mutation in the Drosophila melanogaster selenophosphate synthetase 1 (sps1) gene, which codes for the SelD enzyme of the selenoprotein biosynthesis, affects the Ras/MAPK signalling pathway. The selD(ptuf) mutation dominantly suppresses the phenotypes in the eye and the wing caused by hyperactivation of the Ras/MAPK cassette and the activated forms of the Drosophila EGF receptor (DER) and Sevenless (Sev) receptor tyrosine kinases (RTKs), which signal in the eye and wing, respectively. No dominant interaction is observed with sensitized conditions in the Wnt, Notch, Insulin-Pi3K, and DPP signalling pathways. Our current hypothesis is that selenoproteins selectively modulate the Ras/MAPK signalling pathway through their antioxidant function. This is further supported by the fact that a selenoprotein-independent increase in ROS caused by the catalase amorphic Cat(n1) allele also reduces Ras/MAPK signalling. Here, we present the first evidence for the role of intracellular redox environment in signalling pathways in Drosophila as a whole organism. PMID- 11784001 TI - cGMP enhances the sonic hedgehog response in neural plate cells. AB - The elaboration of distinct cell types during development is dependent on a small number of inductive molecules. Among these inducers is Sonic hedgehog (Shh), which, in combination with other factors, patterns the dorsoventral (DV) axis of the nervous system. The response of a cell is dependent in part on its complement of cyclic nucleotides. cAMP antagonizes Shh signaling, and we examined the influence of cGMP on the Shh response. Cells in chick neural plate explants respond to Shh by differentiating into ventral neural-cell types. Exposure of intermediate-zone explants to cGMP analogs enhanced their response to Shh in a dose-dependent manner. The Shh response was also enhanced in dorsal-zone explants exposed to chick natriuretic peptide (chNP), which stimulates cGMP production by membrane-bound guanylate cyclase (mGC). Addition of chNP to intermediate-zone explants did not enhance the Shh response, consistent with a reported lack of mGC in this region of the neural tube. Finally, the presence of a nitric oxide (NO) sensitive guanylate cyclase (GC) was established by demonstrating cGMP immunoreactivity in neural tissue following NO stimulation of whole chick embryos. Intracellular levels of cGMP and cAMP may thus provide a mechanism through which other factors modulate the Shh response during neural development. PMID- 11784002 TI - Transgenic Xenopus embryos reveal that anterior neural development requires continued suppression of BMP signaling after gastrulation. AB - In vertebrates, BMP signaling before gastrulation suppresses neural development. Later in development, BMP signaling specifies a dorsal and ventral fate in the forebrain and dorsal fate in the spinal cord. It is therefore possible that a change in the competence of the ectoderm to respond to BMP signaling occurs at some point in development. We report that exposure of the anterior neural plate to BMP4 before gastrulation causes suppression of all neural markers tested. To determine the effects of BMP4 after gastrulation, we misexpressed BMP4 using a Pax-6 promoter fragment in transgenic frog embryos and implanted beads soaked in BMP4 in the anterior neural plate. Suppression of most anterior neural markers was observed. We conclude that most neural genes continue to require suppression of BMP signaling into the neurula stages. Additionally, we report that BMP4 and BMP7 are abundantly expressed in the prechordal mesoderm of the neurula stage embryo. This poses the paradox of how the expression of most neural genes is maintained if they can be inhibited by BMP signaling. We show that at least one gene in the anterior neural plate suppresses the response of the ectoderm to BMP signaling. We propose that the suppressive effect of BMP signaling on the expression of neural genes coupled with localized suppressors of BMP signaling result in the fine-tuning of gene expression in the anterior neural plate. PMID- 11784003 TI - Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. AB - pdx1 (pancreatic and duodenal homeobox gene-1), which is expressed broadly in the embryonic pancreas and, later, in a more restricted manner in the mature beta cells in the islets of Langerhans, is essential both for organ formation and beta cell gene expression and function. We carried out a transgenic reporter gene analysis to identify region- and cell type-specific regulatory regions in pdx1. A 14.5-kb pdx1 genomic fragment corrected the glucose intolerance of pdx1(+/-) animals but, moreover, fully rescued the severe gut and pancreas defects in pdx1( /-) embryos. Sequences sufficient to direct reporter expression to the entire endogenous pdx1 expression domain lie within 4.3 kb of 5' flanking DNA. In this region, we identified two distinct fragments that drive reporter gene expression to different sets of islet neuroendocrine cells. One shows pan-endocrine cell specificity, the other is selectively activated in insulin-producing beta cells. The endocrine-specific regulatory regions overlap a localized region of 5' flanking DNA that is remarkably conserved in sequence between vertebrate pdx1 genes, and which has been associated with beta cell-selective expression in cultured cell lines. This region contains potential binding sites for several transcription factors implicated in endodermal development and the pathogenesis of some forms of type-2 diabetes. These results are consistent with our previous proposal that conserved upstream pdx1 sequences exert control over pdx1 during embryonic organogenesis and islet endocrine cell differentiation. We propose that mutations affecting the expression and/or activity of transcription factors operating via these sequences may predispose towards diabetes, at least in part by direct effects on endocrine pdx1 expression. PMID- 11784004 TI - Dorsal pancreas agenesis in N-cadherin- deficient mice. AB - Members of the cadherin family of cell adhesion molecules are thought to be crucial regulators of tissue patterning and organogenesis. During pancreatic ontogeny N-cadherin is initially expressed in the pancreatic mesenchyme and later in pancreatic endoderm. Analysis of N-cadherin-deficient mice revealed that these mice suffer from selective agenesis of the dorsal pancreas. Further analysis demonstrated that the mechanism for the lack of a dorsal pancreas involves an essential function of N-cadherin as a survival factor in the dorsal pancreatic mesenchyme. PMID- 11784005 TI - Germ-soma differentiation in volvox. AB - Volvox carteri is a spherical green alga with a predominantly asexual mode of reproduction and a complete germ-soma division of labor. Its somatic cells are specialized for motility, incapable of dividing, and programmed to die when only a few days old, whereas its gonidia (asexual reproductive cells) are nonmotile, specialized for growth and reproduction, and potentially immortal. When a gonidium is less than 2 days old it divides to produce a juvenile spheroid containing all of the somatic cells and gonidia that will be present in an adult of the next generation. The first visible step in germ-soma differentiation is a set of asymmetric cleavage divisions in the embryo that set apart small somatic initials from their large gonidial-initial sister cells. Three types of genes have been found to play key roles in germ-soma specification. First a set of gls genes act in the embryos to shift cell-division planes, resulting in the asymmetric divisions that set apart the large-small sister-cell pairs. Then a set of lag genes act in the large cells to prevent somatic differentiation, while the regA gene acts in the small cells to prevent reproductive development. An inducible transposon was used to tag and recover some of these and other developmentally important genes. The glsA gene encodes a chaperone-like protein that, like another chaperone that is one of its putative binding partners, is associated with the cell division apparatus, although how this leads to asymmetric division remains to be elucidated. The regA gene encodes a somatic cell-specific nuclear protein that appears to function by repressing genes required for chloroplast biogenesis, thereby preventing somatic cells from growing enough to reproduce. Somatic-cell-specific expression of regA is controlled by three intronic enhancers. PMID- 11784006 TI - Estrogen receptor-alpha knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract. AB - Data indicate that estrogen-dependent and -independent pathways are involved in the teratogenic/carcinogenic syndrome that follows developmental exposure to 17beta-estradiol or diethylstilbestrol (DES), a synthetic estrogen. However, the exact role and extent to which each pathway contributes to the resulting pathology remain unknown. We employed the alphaERKO mouse, which lacks estrogen receptor-alpha (ERalpha), to discern the role of ERalpha and estrogen signaling in mediating the effects of neonatal DES exposure. The alphaERKO provides the potential to expose DES actions mediated by the second known ER, ERbeta, and those that are ER-independent. Wild-type and alphaERKO females were treated with vehicle or DES (2 microg/pup/day for Days 1-5) and terminated after 5 days and 2, 4, 8, 12, and 20 months for biochemical and histomorphological analyses. Assays for uterine expression of the genes Hoxa10, Hoxa11, and Wnt7a shortly after treatment indicated significant decreases in DES-treated wild-type but no effect in the alphaERKO. In contrast, the DES effect on uterine expression of Wnt4 and Wnt5a was preserved in both genotypes, suggesting a developmental role for ERbeta. Adult alphaERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure exhibited in treated wild-type animals, including atrophy, decreased weight, smooth muscle disorganization, and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent vaginal cornification. Therefore, the lack of DES effects on gene expression and tissue differentiation in the alphaERKO provides unequivocal evidence of an obligatory role for ERalpha in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract. PMID- 11784007 TI - Visualizing normal and defective bone development in zebrafish embryos using the fluorescent chromophore calcein. AB - Zebrafish have recently become a model of choice among developmental biologists. This unique model enables both modern molecular and genetic studies to be carried out to identify genes involved in a wide variety of developmental processes. The success of the genetic approach depends largely on the application of an easy and effective screening method to identify interesting mutants. In order to develop a method for visualizing skeletal structures in zebrafish embryos that would be suitable for screening skeletal mutants, we investigated the use of the fluorescent chromophore calcein, which binds specifically to calcified skeletal structures. By using this method, we followed the development of the skeletal structures in zebrafish embryos from day 1 to day 21 postfertilization, and analyzed the effect of bone morphogenetic protein-2 (BMP2) on axial skeleton development. We found the development of the calcified skeletal structure to appear in a progressive fashion from head to tail. Calcified structures in the head (i.e., the jaw) developed first, which were then followed by the axial skeleton in the trunk. Interesting to note was that there appeared to be two domains in the calcification of vertebrae within the axial skeleton. The first three vertebrae were in the first domain; the rest being in the second domain. Compared with Alcian blue staining, we found that calcein staining indeed labels calcified skeletal structures, and, moreover, it is a more sensitive and inclusive method for visualizing skeletal structures. To determine whether calcein staining could also be used to detect abnormal bone development, we ectopically expressed BMP2 in zebrafish notochord cells. We demonstrated that ectopic expression of BMP2 in notochord cells inhibited the development of the axial skeleton. Together, these results clearly demonstrated the sensitivity of calcein staining for visualizing bone structures in developing zebrafish embryos and its effectiveness for screening for mutants that have bone structure defects. PMID- 11784008 TI - FGFR3 expression during development and regeneration of the chick inner ear sensory epithelia. AB - Several studies suggest fibroblast growth factor receptor 3 (FGFR3) plays a role in the development of the auditory epithelium in mammals. We undertook a study of FGFR3 in the developing and mature chicken inner ear and during regeneration of this epithelium to determine whether FGFR3 shows a similar pattern of expression in birds. FGFR3 mRNA is highly expressed in most support cells in the mature chick basilar papilla but not in vestibular organs of the chick. The gene is expressed early in the development of the basilar papilla. Gentamicin treatment sufficient to destroy hair cells in the basilar papilla causes a rapid, transient downregulation of FGFR3 mRNA in the region of damage. In the initial stages of hair cell regeneration, the support cells that reenter the mitotic cycle in the basilar papilla do not express detectable levels of FGFR3 mRNA. However, once the hair cells have regenerated in this region, the levels of FGFR3 mRNA and protein expression rapidly return to approximate those in the undamaged epithelium. These results indicate that FGFR3 expression changes after drug-induced hair cell damage to the basilar papilla in an opposite way to that found in the mammalian cochlea and may be involved in regulating the proliferation of support cells. PMID- 11784009 TI - Diverse genes expressed in distinct regions of the trunk epithelium define a monolayer cellular template for construction of the oikopleurid house. AB - The filter-feeding house secreted by urochordate Appendicularians is among the most complex extracellular structures constructed by any organism. This structure allows the Appendicularia to exploit a wide range of food particle sizes, including nanoplankton and submicrometer colloids, establishing them as an important and abundant component of marine zooplankton communities throughout the world. The oikoplastic epithelium, a monolayer of cells covering the trunk of the animal, is responsible for secretion of the house. The epithelium has a fixed number of cells, organized in distinct fields, characterized by defined cell shapes and nuclear morphologies. Certain structures in the house appear to be spatially linked to these different fields of cells. Using cDNA representation difference analysis (cDNA RDA) on whole animals at two different developmental stages separated by the metamorphic tailshift event, we isolated four families of genes (oikosins) that are expressed only from specific subregions of the oikoplastic epithelium. The molecular patterns defined by oikosin gene expression establish the epithelium as an ideal and easily accessible monolayer cellular template for exploring coordinate regulation of gene expression, cell-cell interactions involved in pattern formation, gene/genome amplification, and the role of temporal changes in nuclear architecture in regulating gene expression. PMID- 11784010 TI - Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process. AB - The origin of resident (noninflammatory) macrophages in vertebrate tissues is still poorly understood. In the zebrafish embryo, we recently described a specific lineage of early macrophages that differentiate in the yolk sac before the onset of blood circulation. We now show that these early macrophages spread in the whole cephalic mesenchyme, and from there invade epithelial tissues: epidermis, retina, and brain--especially the optic tectum. In the panther mutant, which lacks a functional fms (M-CSF receptor) gene, early macrophages differentiate and behave apparently normally in the yolk sac, but then fail to invade embryonic tissues. Our video recordings then document for the first time the behavior of macrophages in the invaded tissues, revealing the striking propensity of early macrophages in epidermis and brain to wander restlessly among epithelial cells. This unexpected behavior suggests that tissue macrophages may be constantly "patrolling" for immune and possibly also developmental and trophic surveillance. At 60 h post-fertilization, all macrophages in the brain and retina undergo a specific phenotypic transformation, into "early (amoeboid) microglia": they become more highly endocytic, they down-regulate the L-plastin gene, and abruptly start expressing high levels of apolipoprotein E, a well-known neurotrophic lipid carrier. PMID- 11784011 TI - Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development. AB - Branching morphogenesis of the ureteric bud (UB) [induced by the metanephric mesenchyme (MM)] is necessary for normal kidney development. The role of integrins in this complex developmental process is not well understood. However, the recent advent of in vitro model systems to study branching of UB cells and isolated UB tissue makes possible a more detailed analysis of the integrins involved. We detected integrin subunits alpha3, alpha6, beta1, and beta4 in both the UB and cells derived from the early UB. Blocking the function of each of these integrin subunits individually markedly inhibited branching morphogenesis in cell culture models. However, inhibiting individual integrin function with blocking antibodies in whole kidney and isolated UB culture only partially inhibited UB branching morphogenesis, suggesting that, in these more complex in vitro systems, multiple integrins are involved in the branching program. In whole organ and isolated bud culture, marked retardation of UB branching was observed only when both alpha3 and alpha6 integrin subunits were inhibited. The alpha6 integrin subunit can be expressed as both alpha6beta1 and alpha6beta4, and both of these beta subunits are important for UB branching morphogenesis in both cell and organ culture. Furthermore, laminin-5, a common ligand for integrins alpha3beta1 and alpha6beta4, was detected in the developing UB and shown to be required for normal UB branching morphogenesis in whole embryonic kidney organ culture as well as isolated UB culture. Together, these data from UB cell culture, organ culture, and isolated UB culture models indicate that both integrin alpha3 and alpha6 subunits play a direct role in UB branching morphogenesis, as opposed to being modulators of the inductive effects of mesenchyme on UB development. Furthermore the data are consistent with a role for laminin-5, acting through its alpha3beta1 and/or alpha6beta4 integrin receptors, in UB branching during nephrogenesis. These data may help to partially explain the renal phenotype seen in integrin alpha3 and alpha3/alpha6 subunit-deficient animals. PMID- 11784012 TI - The role of BMP signaling in outgrowth and patterning of the Xenopus tail bud. AB - Tail bud formation in Xenopus depends on interaction between a dorsal domain (dorsal roof) expressing lunatic fringe and Notch, and a ventral domain (posterior wall) expressing the Notch ligand Delta. Ectopic expression of an activated form of Notch, Notch ICD, by means of an animal cap graft into the posterior neural plate, results in the formation of an ectopic tail-like structure containing a neural tube and fin. However, somites are never formed in these tails. Here, we show that BMP signaling is activated in the posterior wall of the tail bud and is involved in the formation of tail somites from this region. Grafts into the posterior neural plate, in which BMP signaling is activated, will form tail-like outgrowths. Unlike the Notch ICD tails, the BMP tails contain well-organized somites as well as neural tube and fin, with the graft contributing to both somites and neural tube. Through a variety of epistasis-type experiments, we show that the most likely model involves a requirement for BMP signaling upstream of Notch activation, resulting in formation of the secondary neural tube, as well as a Notch-independent pathway leading to the formation of tail somites from the posterior wall. PMID- 11784013 TI - Profiles of maternally expressed genes in fertilized eggs of Ciona intestinalis. AB - A set of 1,378 expressed sequence tags (ESTs), both the 5'-most and 3'-most ends, derived from Ciona intestinalis fertilized eggs was categorized into 1,003 independent clusters. When compared with sequences in databases, 452 of the clusters showed significant matches with reported proteins, while 190 showed matches with putative proteins for which there is not enough information to categorize their function, and 361 had no significant similarities to known proteins. Sequence similarity analyses of the 452 clusters in relation to the biological function as well as the structure of the message population at this stage demonstrated that 362 of them have functions that many kinds of cells use, 65 are associated with cell-cell communication, including a candidate cDNA for sonic hedgehog, and 25 are transcription factors. Sequence prevalence distribution analysis demonstrated that the great majority (78%) of the mRNAs are rare mRNAs or are represented by a single clone/cluster. All of the 1,003 clusters were subjected to whole-mount in situ hybridization to analyze the distribution of the maternal mRNAs in fertilized eggs, and a total of 329 genes showed localized distribution of the mRNAs: 16 showed cortical localization, 12 showed mitochondrial-like distribution, 99 crescent-like distribution, 63 partial localization, and 139 weak localization. When the distribution pattern of all the maternally expressed mRNAs was examined in the 8-cell stage embryos, it became evident that 248 genes which have localized mRNA patterns at the fertilized egg stage lose their localized distribution by the 8-cell stage. In contrast, 13 genes newly gain a localized pattern by the 8-cell stage. In addition, a total of 39 genes showed distinct in situ signals in the nucleus of blastomeres of the 8 cell stage embryo, suggesting early zygotic expression of these genes by this stage. These results suggest that complicated cytoplasmic movements are associated with the characteristic distribution of maternal mRNAs, which in turn support proper embryonic axis formation and establishment of the genetic network for embryonic cell specification. PMID- 11784015 TI - Intracellular BMP signaling regulation in vertebrates: pathway or network? AB - Bone morphogenetic proteins (BMPs), members of the TGF-beta superfamily of secreted signaling molecules, have important functions in many biological contexts. They bind to specific serine/threonine kinase receptors, which transduce the signal to the nucleus through Smad proteins. The question of how BMPs can have such diverse effects while using the same canonical Smad pathway has recently come closer to an answer at the molecular level. Nuclear cofactors have been identified that cooperate with the Smads in regulating specific target genes depending on the cellular context. In addition, the pivotal role BMP signaling plays is underscored by the identification of factors that regulate members of this pathway at the cell surface, in the cytoplasm, and in the nucleus. Many of these factors are BMP-inducible and inhibit the BMP pathway, thus establishing negative feedback loops. Members of the BMP-Smad pathway can also physically interact with components of other signaling pathways to establish crosstalk. Finally, there is accumulating evidence that an alternative pathway involving MAP kinases can transduce BMP signals. The evidence and implications of these findings are discussed with an emphasis on early embryonic development of Xenopus and vertebrates. PMID- 11784016 TI - Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling activity during chick embryogenesis. AB - Hedgehog (Hh) signaling in vertebrates controls patterning and differentiation of a broad range of tissues during development. The Hh receptor Patched (Ptc) is a critical regulator of signaling, maintaining active repression of the pathway in the absence of stimulation, limiting excess diffusion of ligand, and providing an efficient negative feedback mechanism for fine-tuning the responsiveness of receiving cells. Two distinct Ptc genes have been isolated from several vertebrates. Here, we describe the cloning of a second Ptc gene from chick (Ptc2). We show that Ptc1 and Ptc2 are both upregulated at sites of active Hh signaling but that the expression patterns of these genes only partially overlap, thus providing distinct readouts of Hh pathway stimulation. We also show that chick Ptc2 is expressed in the posterior apical ectodermal ridge (AER) of the limb bud in a pattern similar to Fgf4 and that the induction of Ptc2 within the AER, like that of Fgf4, is mediated via antagonism of BMP signaling. The differential responsiveness of cells to Hh pathway stimulation (as marked by the differential induction of Ptc genes) suggests heterogeneity in the mechanisms by which Hh signals are transduced within different populations of receiving cells. PMID- 11784017 TI - The avian telencephalic subpallium originates inhibitory neurons that invade tangentially the pallium (dorsal ventricular ridge and cortical areas). AB - Recent data on the development of the mammalian neocortex support that the majority of its inhibitory GABAergic interneurons originate within the subpallium (ganglionic eminences). Support for such tangential migration into the pallium has come from experiments using fluorescent tracers or lineage analysis with retrovirus, and the phenotypes of mutant mice with different abnormalities in the developing subpallium. In the present study, we describe tangential migration of subpallial-derived neurons in the developing chick telencephalon. Using quail chick grafts, we precisely identified the neuroepithelial origin, time-course, and pathways of migration, as well as the identity and relative distribution of the diverse tangentially migrated neurons. The analysis of selective grafts of the pallidal and striatal primordia allowed us to determine the relative contribution of each primordium to the population of migrating neurons. Moreover, we found that, like in mammals, the vast majority of the GABAergic and calbindin immunoreactive neurons within the pallium (dorsal ventricular ridge and cortical areas) have an extracortical, subpallial origin. Our results suggest that the telencephalon of birds and mammals share developmental mechanisms for the origin and migration of their cortical interneurons, which probably first evolved at an earlier stage in the radiation of vertebrates than was thought before. PMID- 11784014 TI - A mouse acrosomal cortical matrix protein, MC41, has ZP2-binding activity and forms a complex with a 75-kDa serine protease. AB - Sperm with a large acrosome such as that of guinea pigs and hamsters have a subdomain structure in the anterior acrosome, but the mouse acrosome looks homogeneous and its matrix has not been precisely analyzed. The intra-acrosomal protein MC41 is localized in the cortical region of the mouse anterior acrosome, suggesting a subdomain structure in the mouse acrosome. Thus, the present study was undertaken to analyze the mouse acrosomal matrix using an anti-MC41 antibody. When mouse sperm were treated with 2% Triton X-100, Triton-insoluble matrix components remained in the acrosomal cortical region. Immunogold for MC41 labeled the Triton X-100 and high-salt-insoluble matrix components, demonstrating that MC41 is a subdomain-specific acrosomal matrix protein. We further examined interactions of MC41 with acrosomal proteases and zona proteins. A serine protease of 75 kDa was associated with MC41 under low-salt conditions, presumably forming a complex. Far Western blotting technique indicated that MC41 bound to both ZP2 and ZP2(f) in the presence of high-salt-soluble sperm proteins. In acrosome-reacting sperm, MC41 was present on the hybrid vesicles formed by the fusion of the plasma and outer acrosomal membranes. Presumably, MC41 has a significant role in secondary sperm-zona binding during the acrosomal reaction. PMID- 11784018 TI - Fate map of the avian anterior forebrain at the four-somite stage, based on the analysis of quail-chick chimeras. AB - To better understand the topological organization of the primordia within the anterior forebrain, we made a fate map of the rostral neural plate in the chick. Homotopic grafts at the four-somite stage were allowed to survive for up to 9 days to enable an analysis of definitive brain structures. In some cases, the topography of the grafted neuroepithelia was compared with gene expression patterns. The midpoint of the anterior neural ridge maps upon the anterior commissure in the closed neural tube, continuing concentrically into the preoptic area and optic field. Non-neural epithelium just in front of this median ridge gives rise to the adenohypophysis. Areas for the presumptive pallial commissure, septum, and prosencephalic choroidal tissue lie progressively more posteriorly along the ridge, peripheral to the telencephalic entopeduncular and striatopallidal primordia (the subpallium), and the pallium (olfactory bulb, dorsal ventricular ridge, and cortical domains). Subpallial structures lie topologically anterior to the pallial formations, and both are concentric to the septum. Within the pallium, the major cortical domains (Wulst and caudolateral, parahippocampal, and hippocampal cortices) appear posterior to the dorsal ventricular ridge. The amygdaloid region appears concentrically across both the subpallial and pallial regions. This fate map shows that the arrangement of the prospective primordia in the neural plate is basically a flattened representation of topological relationships present in the mature brain, though marked phenomena of differential growth and selective tangential migration of some cell populations complicate the histogenetic constitution of the mature telencephalon. PMID- 11784019 TI - A gap junctionally transmitted epithelial cell signal regulates endocytic yolk uptake in Oncopeltus fasciatus. AB - For endocytic uptake of vitellogenins, developing oocytes of Oncopeltus require a soluble, diffusible molecular signal from their surrounding epithelial cells, and this signal must be transmitted through open gap junctions. Hormonal stimulation triggering synthesis and processing of vitellogenins into mature insect yolk spheres has been intensely studied, and follicle epithelial cells are known in several insects to contribute to the blood products which are endocytosed along with vitellogenins synthesized in the fat bodies. However, there has been little evidence that direct gap junctional communication is a requirement for endocytic activity by oocytes. In untreated control follicles, both electrical and dye coupling occur, and follicles incubated in vitro in physiological salt solution containing small amounts of blood and fluorescent dye produce fluorescently labeled nascent yolk spheres. Labeled yolk spheres were visible in both sectioned material, and, with (Laser) Confocal Scanning, in living material. Dye coupling was abolished by treatment with either 1 mM octanol, 0.5 mM ethyl methanesulfonate (EMS), or cytoplasmic acidification, with coupling coefficients also being affected as each of these gap junction antagonists down-regulated the connexons. With each of these treatments, after gap junctions were down regulated, receptor-mediated endocytic uptake of blood-born vitellogenins came to a halt. Furthermore, Oncopeltus follicles with endocytic activity blocked in this manner could be rescued by microinjection of the soluble fraction of lysed epithelial cell cytoplasm, confirming that the process depended upon a molecular signal from the epithelial cells. PMID- 11784020 TI - Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration. AB - Myogenesis in the embryo and the adult mammal consists of a highly organized and regulated sequence of cellular processes to form or repair muscle tissue that include cell proliferation, migration, and differentiation. Data from cell culture and in vivo experiments implicate both FGFs and HGF as critical regulators of these processes. Both factors require heparan sulfate glycosaminoglycans for signaling from their respective receptors. Since syndecans, a family of cell-surface transmembrane heparan sulfate proteoglycans (HSPGs) are implicated in FGF signaling and skeletal muscle differentiation, we examined the expression of syndecans 1-4 in embryonic, fetal, postnatal, and adult muscle tissue, as well as on primary adult muscle fiber cultures. We show that syndecan-1, -3, and -4 are expressed in developing skeletal muscle tissue and that syndecan-3 and -4 expression is highly restricted in adult skeletal muscle to cells retaining myogenic capacity. These two HSPGs appear to be expressed exclusively and universally on quiescent adult satellite cells in adult skeletal muscle tissue, suggesting a role for HSPGs in satellite cell maintenance or activation. Once activated, all satellite cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration. Inhibition of HSPG sulfation by treatment of intact myofibers with chlorate results in delayed proliferation and altered MyoD expression, demonstrating that heparan sulfate is required for proper progression of the early satellite cell myogenic program. These data suggest that, in addition to providing potentially useful new markers for satellite cells, syndecan-3 and syndecan-4 may play important regulatory roles in satellite cell maintenance, activation, proliferation, and differentiation during skeletal muscle regeneration. PMID- 11784021 TI - A spontaneous mouse mutation, mesenchymal dysplasia (mes), is caused by a deletion of the most C-terminal cytoplasmic domain of patched (ptc). AB - A recessive mouse mutation, mesenchymal dysplasia (mes), which arose spontaneously on Chromosome 13, causes excess skin, increased body weight, and mild preaxial polydactyly. Fine gene mapping in this study indicated that mes is tightly linked to patched (ptc) that encodes a transmembrane receptor protein for Shh. Molecular characterization of the ptc gene of the mes mutant and an allelism test using a ptc knockout allele (ptc(-)) demonstrated that mes is caused by a deletion of the most C-terminal cytoplasmic domain of the ptc gene. Since mes homozygous embryos exhibit normal spinal cord development as compared with ptc(-) homozygotes, which die around 10 dpc with severe neural tube defects, the C terminal cytoplasmic domain lost in mes mutation is dispensable for inhibition of Shh signaling in early embryogenesis. However, compound heterozygotes of ptc(-) and mes alleles, which survive up to birth and die neonatally, had increased body weight and exhibited abnormal anteroposterior axis formation of the limb buds. These findings indicate that Ptc is a negative regulator of body weight and ectopic activation of Shh signaling in the anterior mesenchyme of the limb buds, and that the C-terminal cytoplasmic domain of Ptc is involved in its repressive action. PMID- 11784022 TI - Induction of ascidian peripheral neuron by vegetal blastomeres. AB - Ascidian tadpole larvae have a similar dorsal tubular nervous system as vertebrates. The induction of brain formation from a4.2-derived (a-line) cells requires signals from the A4.1-derived (A-line) cells. However, little is known about the mechanism underlying the development of the larval peripheral nervous system due to the lack of a suitable molecular marker. Gelsolin, an actin-binding protein, is specifically expressed in epidermal sensory neurons (ESNs) that mainly constitute the entire peripheral nervous system of the ascidian young tadpoles. Here, we address the role of cell interactions in the specification of ESNs using immunostaining with an anti-gelsolin antibody. Animal half (a4.2- and b4.2-derived) embryos did not give rise to any gelsolin-positive neurons, indicating that differentiation of ESNs requires signals from vegetal cells. Cell isolation experiments showed that A4.1 blastomeres induce gelsolin-positive neurons from a-line cells but not from b4.2-derived (b-line) cells. On the other hand, B4.1 blastomeres induce gelsolin-positive neurons both from b-line cells and a-line cells. This is in sharp contrast to the specification of brain cells which is not affected by the ablation of B4.1-derived (B-line) cells. Furthermore, basic fibroblast growth factor (bFGF) induced ESNs from the a-line cells and b-line cells in the absence of vegetal cells. Their competence to form ESNs was lost between the 110-cell stage and the neurula stage. Our results suggested that the specification of the a-line cells and b-line cells into ESNs is controlled by distinct inducing signals from the anterior and posterior vegetal blastomeres. ESNs in the trunk appear to be derived from the a8.26 blastomeres aligning on the edge of presumptive neural region where ascidian homologue of Pax3 is expressed. These findings highlight the close similarity of ascidian ESNs development with that of vertebrate placode and neural crest. PMID- 11784023 TI - Expression cloning of Xenopus Os4, an evolutionarily conserved gene, which induces mesoderm and dorsal axis. AB - Multiple factors, including members of the FGF, TGF beta, and Wnt family of proteins, are important mediators in the regulation of dorsal-ventral pattern formation during vertebrate development. By using an expression cloning approach to identify novel factors that could regulate dorsal-ventral patterning in the Xenopus embryo, we isolated the Xenopus homologue of the human Os4 gene by virtue of its ability to induce a secondary dorsal axis. While Os4 homologues have been identified in a variety of species, and human Os4 is overexpressed in human tumors, the biological function of Os4 is unknown. To explore the mechanism by which Xenopus Os4 (XOs4) induces a secondary dorsal axis, we used Xenopus explant and whole-embryo assays. The secondary axis induced by XOs4 is distinct from that induced by activation of Wnt or FGF pathways but similar to that induced by inhibition of BMP signaling or activation of an Activin pathway. However, XOs4 did not inhibit BMP signaling in dissociated animal cap explants, indicating that XOs4 does not inhibit BMP signaling. Similar to activation of an Activin-like pathway, expression of XOs4 induces molecular markers for mesoderm in animal cap explants, although expression of gastrula-stage mesodermal markers was very weak and substantially delayed. Yet, XOs4 does not require activity of the Activin signal-transduction pathway for mesoderm induction as dominant-negative components of the Activin/Nodal/Vg1 pathway did not prevent XOs4-mediated induction of mesodermal derivatives. Finally, like Activin/Nodal/Vg1 pathways, XOs4 requires FGF signaling for expression of mesoderm markers. Results presented in this study demonstrate that XOs4 can induce mesoderm and dorsalize ventral mesoderm resulting in ectopic dorsal axis formation, suggesting a role for this large evolutionarily conserved gene family in early development. PMID- 11784024 TI - The role of Brachyury (T) during gastrulation movements in the sea urchin Lytechinus variegatus. AB - The studies described here sought to identify and characterize genes involved in the gastrulation and morphogenetic movements that occur during sea urchin embryogenesis. An orthologue of the T-box family transcription factor, Brachyury, was cloned through a candidate gene approach. Brachyury (T) is the founding member of this T-box transcription factor family and has been implicated in gastrulation movements in Xenopus, zebrafish, and mouse embryogenesis. Polyclonal serum was generated to LvBrac in order to characterize protein expression. LvBrac initially appears at mesenchyme blastula stage in two distinct regions with embryonic expression perduring until pluteus stage. Vegetally, LvBrac expression is in endoderm and lies circumferentially around the blastopore. This torus shaped area of LvBrac expression remains constant in size as endoderm cells express LvBrac upon moving into that circumference and cease LvBrac expression as they leave the circumference. Vegetal expression remains around the anus through pluteus stage. The second domain of LvBrac expression first appears broadly in the oral ectoderm at mesenchyme blastula stage and at later embryonic stages is refined to just the stomodael opening. Vegetal LvBrac expression depends on autonomous beta-catenin signaling in macromeres and does not require micromere or veg2-inductive signals. It was then determined that LvBrac is necessary for the morphogenetic movements occurring in both expression regions. A dominant interfering construct was generated by fusing the DNA binding domain of LvBrac to the transcriptional repression module of the Drosophila Engrailed gene in order to perturb gene function. Microinjection of mRNA encoding this LvBrac-EN construct resulted in a block in gastrulation movements but not expression of endoderm and mesoderm marker genes. Furthermore, injection of LvBrac-EN into one of two blastomeres resulted in normal gastrulation movements of tissues derived from the injected blastomere, indicating that LvBrac downstream function may be nonautonomous during sea urchin gastrulation. PMID- 11784027 TI - RNAi As a tool for understanding germline development in Caenorhabditis elegans: uses and cautions. AB - RNA-mediated genetic interference (RNAi) has become a very useful tool for analyzing gene function in development and other processes. RNAi can be used as a complement to traditional genetic studies or as a primary means of determining biological function. However, the efficacy of RNAi depends on a variety of factors that the researcher must take into consideration. This review focuses on germline development in the nematode, Caenorhabditis elegans, and discusses the uses and limitations of RNAi in providing new information about gene function as well as the possible endogenous role RNAi plays in germline physiology. PMID- 11784025 TI - The Wnt/beta-catenin pathway posteriorizes neural tissue in Xenopus by an indirect mechanism requiring FGF signalling. AB - In order to identify factors involved in posteriorization of the central nervous system, we undertook a functional screen in Xenopus animal cap explants which involved coinjecting noggin RNA together with pools of RNA from a chick somite cDNA library. In the course of this screen, we isolated a clone encoding a truncated form of beta-catenin, which induced posterior neural and dorsal mesodermal markers when coinjected with noggin in animal caps. Similar results were obtained with Xwnt-8 and Xwnt-3a, suggesting that these effects are a consequence of activating the canonical Wnt signalling pathway. To investigate whether the activation of posterior neural markers requires mesoderm induction, we performed experiments using a chimeric inducible form of beta-catenin. Activation of this protein during blastula stages resulted in the induction of both posterior neural and mesodermal markers, while activation during gastrula stages induced only posterior neural markers. We show that this posteriorizing activity occurs by an indirect and noncell-autonomous mechanism requiring FGF signalling. PMID- 11784026 TI - Trophoblast-specific expression and function of the integrin alpha 7 subunit in the peri-implantation mouse embryo. AB - For implantation and placentation to occur, mouse embryo trophoblast cells must penetrate the uterine stroma to make contact with maternal blood vessels. A major component of the uterine epithelial basement membrane and underlying stromal matrix with which they interact is the extracellular matrix protein laminin. We have identified integrin alpha 7 beta 1 as a major receptor for trophoblast laminin interactions during implantation and yolk sac placenta formation. It is first expressed by trophectoderm cells of the late blastocyst and by all trophectoderm descendants in the early postimplantation embryo through E8.5, then disappears except in cells at the interface between the allantois and the ectoplacental plate. Integrin alpha 7 expression is a general characteristic of the early differentiation stages of rodent trophoblast, given that two different cultured trophoblast cell lines also express this integrin. Trophoblast cells interact with at least three different laminin isoforms (laminins 1, 2/4, and 10/11) in the blastocyst and in the uterus at the time of implantation. Outgrowth assays using function-blocking antibodies show that alpha 7 beta 1 is the major trophoblast receptor for laminin 1 and a functional receptor for laminins 2/4 and 10/11. When trophoblast cells are cultured on substrates of these three laminins, they attach and spread on all three, but show decreased proliferation on laminin 1. These results show that the alpha 7 beta 1 integrin is expressed by trophoblast cells and acts as receptor for several isoforms of laminin during implantation. These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm proliferation and differentiation. PMID- 11784028 TI - The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. AB - Nkx2.5/Csx and dHAND/Hand2 are conserved transcription factors that are coexpressed in the precardiac mesoderm and early heart tube and control distinct developmental events during cardiogenesis. To understand whether Nkx2.5 and dHAND may function in overlapping genetic pathways, we generated mouse embryos lacking both Nkx2.5 and dHAND. Mice heterozygous for mutant alleles of Nkx2.5 and dHAND were viable. Although single Nkx2.5 or dHAND mutants have a morphological atrial and single ventricular chamber, Nkx2.5(-/-)dHAND(-/-) mutants had only a single cardiac chamber which was molecularly defined as the atrium. Complete ventricular dysgenesis was observed in Nkx2.5(-/-)dHAND(-/-) mutants; however, a precursor pool of ventricular cardiomyocytes was identified on the ventral surface of the heart tube. Because Nkx2.5 mutants failed to activate eHAND expression even in the early precardiac mesoderm, the Nkx2.5(-/-)dHAND(-/-) phenotype appears to reflect an effectively null state of dHAND and eHAND. Cell fate analysis in dHAND mutants suggests a role of HAND genes in survival and expansion of the ventricular segment, but not in specification of ventricular cardiomyocytes. Our molecular analyses also revealed the cooperative regulation of the homeodomain protein, Irx4, by Nkx2.5 and dHAND. These studies provide the first demonstration of gene mutations that result in ablation of the entire ventricular segment of the mammalian heart, and reveal essential transcriptional pathways for ventricular formation. PMID- 11784029 TI - Sequential docking, molecular differentiation, and positioning of T-Tubule/SR junctions in developing mouse skeletal muscle. AB - Skeletal muscle Ca(2+) release units (CRUs) are junctions of the surface membrane/T-tubule system and the sarcoplasmic reticulum (SR) that function in excitation-contraction coupling. They contain high concentrations of dihydropyridine receptors (DHPRs) in the T-tubules and of ryanodine receptors (RyR) in the SR and they are positioned at specific locations in the sarcomere. In order to characterize the sequence of developmental steps leading to the specific molecular and structural organization of CRUs, we applied a range of imaging techniques that allowed us to follow the differentiation of the membrane compartments and the expression of junctional proteins in developing mouse diaphragm muscle. We find that docking of the two membrane systems precedes the incorporation of the RyRs into the junctions, and that T-tubule/SR junctions are formed and positioned at the I-A interface at a stage when the orientation of T tubule is predominantly longitudinal. Thus, the sequence of developmental events is first the docking of T-tubules and SR, secondly the incorporation of RyR in the junctions, thirdly the positioning of the junctions in the sarcomere, and only much later the transverse orientation of the T-tubules. These sequential stages suggests an order of inductive processes for the molecular differentiation and structural organization of the CRUs in skeletal muscle development. PMID- 11784030 TI - zipper Nonmuscle myosin-II functions downstream of PS2 integrin in Drosophila myogenesis and is necessary for myofibril formation. AB - Nonmuscle myosin-II is a key motor protein that drives cell shape change and cell movement. Here, we analyze the function of nonmuscle myosin-II during Drosophila embryonic myogenesis. We find that nonmuscle myosin-II and the adhesion molecule, PS2 integrin, colocalize at the developing muscle termini. In the paradigm emerging from cultured fibroblasts, nonmuscle actomyosin-II contractility, mediated by the small GTPase Rho, is required to cluster integrins at focal adhesions. In direct opposition to this model, we find that neither nonmuscle myosin-II nor RhoA appear to function in PS2 clustering. Instead, PS2 integrin is required for the maintenance of nonmuscle myosin-II localization and we show that the cytoplasmic tail of the beta(PS) integrin subunit is capable of mediating this PS2 integrin function. We show that embryos that lack zygotic expression of nonmuscle myosin-II fail to form striated myofibrils. In keeping with this, we demonstrate that a PS2 mutant that specifically disrupts myofibril formation is unable to mediate proper localization of nonmuscle myosin-II at the muscle termini. In contrast, embryos that lack RhoA function do generate striated muscles. Finally, we find that nonmuscle myosin-II localizes to the Z-line in mature larval muscle. We suggest that nonmuscle myosin-II functions at the muscle termini and the Z-line as an actin crosslinker and acts to maintain the structural integrity of the sarcomere. PMID- 11784031 TI - Role of CtBP in transcriptional repression by the Drosophila giant protein. AB - The giant protein is a short-range transcriptional repressor that refines the expression pattern of gap and pair-rule genes in the Drosophila blastoderm embryo. Short-range repressors including knirps, Kruppel, and snail utilize the CtBP cofactor for repression, but it is not known whether a functional interaction with CtBP is a general property of all short-range repressors. We studied giant repression activity in a CtBP mutant and find that this cofactor is required for giant repression of some, but not all, genes. While targets of giant such as the even-skipped stripe 2 enhancer and a synthetic lacZ reporter show clear derepression in the CtBP mutant, another giant target, the hunchback gene, is expressed normally. A more complex situation is seen with regulation of the Kruppel gene, in which one enhancer is repressed by giant in a CtBP-dependent manner, while another is repressed in a CtBP-independent manner. These results demonstrate that giant can repress both via CtBP-dependent and CtBP-independent pathways, and that promoter context is critical for determining giant-CtBP functional interaction. To initiate mechanistic studies of the giant repression activity, we have identified a minimal repression domain within giant that encompasses residues 89-205, including an evolutionarily conserved region bearing a putative CtBP binding motif. PMID- 11784032 TI - Systematic screening and expression analysis of the head organizer genes in Xenopus embryos. AB - We describe here a systematic screen of an anterior endomesoderm (AEM) cDNA library to isolate novel genes which are expressed in the head organizer region. After removing clones which hybridized to labeled cDNA probes synthesized with total RNA from a trunk region of tailbud embryos, the 5' ends of 1039 randomly picked cDNA clones were sequenced to make expressed sequence tags (ESTs), which formed 754 tentative unique clusters. Those clusters were compared against public databases and classified according to similarities found to other genes and gene products. Of them, 151 clusters were identified as known Xenopus genes, including eight organizer-specific ones (5.3%). Gene expression pattern screening was performed for 198 unique clones, which were selected because they either have no known function or are predicted to be developmental regulators in other species. The screen revealed nine possible organizer-specific clones (4.5%), four of which appeared to be expressed in the head organizer region. Detailed expression analysis from gastrula to neurula stages showed that these four genes named crescent, P7E4 (homologous to human hypothetical genes), P8F7 (an unclassified gene), and P17F11 (homologous to human and Arabidopsis hypothetical genes) demarcate spatiotemporally distinct subregions of the AEM corresponding to the head organizer region. These results indicate that our screening strategy is effective in isolating novel region-specific genes. PMID- 11784033 TI - Multiple pathways governing Cdx1 expression during murine development. AB - Cdx1 encodes a mammalian homeobox gene involved in vertebral patterning. Retinoic acid (RA) is likewise implicated in vertebral patterning. We have previously shown that Cdx1 is a direct retinoid target gene, suggesting that Cdx1 may convey some of the effects of retinoid signaling. However, RA appears to be essential for only early stages of Cdx1 expression, and therefore other factors must be involved in maintaining later stages of expression. Based on function and pattern of expression, Wnt family members, in particular Wnt3a, are candidates for regulation of expression of Cdx1. Consistent with this, we confirm prior results which demonstrated that Cdx1 can be directly regulated by Wnt signaling, and identify functional LEF/TCF response motifs essential for this response. We also find that Cdx1 expression is markedly attenuated in a stage- and tissue-specific fashion in the Wnt3a hypomorph vestigial tail, and present data demonstrating that Wnt3a and RA synergize strongly to activate Cdx1. Finally, we show that Cdx1 positively regulates its own expression. These data prompt a model whereby retinoid and Wnt signaling function directly and synergistically to initiate Cdx1 expression in the caudal embryo. Expression is then maintained, at least in part, by an autoregulatory mechanism at later stages. PMID- 11784034 TI - Hypaxial muscle migration during primary myogenesis in Xenopus laevis. AB - In contrast to many vertebrates, the ventral body wall muscles and limb muscles of Xenopus develop at different times. The ventral body wall forms in the tadpole, while limb (appendicular) muscles form during metamorphosis to the adult frog. In organisms that have been examined thus far, a conserved mechanism has been shown to control migratory muscle precursor specification, migration, and differentiation. Here, we show that the process of ventral body wall formation in Xenopus laevis is similar to hypaxial muscle development in chickens and mice. Cells specified for the migratory lineage display an upregulation of pax3 in the ventro-lateral region of the somite. These pax3-positive cells migrate ventrally, away from the somite, and undergo terminal differentiation with the expression of myf-5, followed by myoD. Several other genes are selectively expressed in the migrating muscle precursor population, including neural cell adhesion molecule (NCAM), Xenopus kit related kinase (Xkrk1), and Xenopus SRY box 5 (sox5). We have also found that muscle precursor migration is highly coordinated with the migration of neural crest-derived melanophores. However, by extirpating neural crest at an early stage and allowing embryos to develop, we determined that muscle precursor migration is not dependent on physical or genetic interaction with melanophores. PMID- 11784035 TI - Microtubule patterning during meiotic maturation in mouse oocytes is determined by cell cycle-specific sorting and redistribution of gamma-tubulin. AB - The topography of microtubule assembly events during meiotic maturation of animal oocytes demands tight spatial control and temporal precision. To better understand what regulates the timing and location of microtubule assembly, synchronously maturing mouse oocytes were evaluated with respect to gamma tubulin, pericentrin, and total tubulin polymer fractions at specific stages of meiotic progression. gamma-Tubulin remained associated with cytoplasmic centrosomes through diakinesis of meiosis-1. Following chromatin condensation and perinuclear centrosome aggregation, gamma-tubulin relocated to a nuclear lamina bounded compartment in which meiosis-1 spindle assembly occurred. gamma-Tubulin was stably associated with the meiotic spindle from prometaphase-1 through to anaphase-2, but also exhibited cell cycle-specific relocalization to cytoplasmic centrosomes. Specifically, anaphase onset of both meiosis-1 and -2 was characterized by the concomitant appearance of gamma-tubulin and microtubule nucleation in subcortical centrosomes. Brief pulses of taxol applied at specific cell cycle stages enhanced detection of gamma-tubulin compartmentalization, consistent with a gamma-tubulin localization-dependent spatial restriction of microtubule assembly during meiotic progression. In addition, a taxol pulse during meiotic resumption impaired subsequent gamma-tubulin sorting, resulting in monopolar spindle formation and cell cycle arrest in meiosis-1; despite cell cycle arrest, polar body extrusion occurred roughly on schedule. Therefore, sorting of gamma-tubulin is involved in both the timing of location of meiotic spindle assembly as well as the coordination of karyokinesis and cytokinesis in mouse oocytes. PMID- 11784036 TI - BCLW mediates survival of postmitotic Sertoli cells by regulating BAX activity. AB - Male mice deficient in BCLW, a death-protecting member of the BCL2 family, are sterile due to an arrest in spermatogenesis that is associated with a gradual loss of germ cells and Sertoli cells from the testis. As Bclw is expressed in both Sertoli cells and diploid male germ cells, it has been unclear which of these cell types requires BCLW in a cell-autonomous manner for survival. To determine whether death of Sertoli cells in Bclw mutants is influenced by the protracted loss of germ cells, we examined testes from Bclw/c-kit double mutant mice, which lack germ cells from birth. Loss of BCLW-deficient Sertoli cells occurs in the absence of germ cells, indicating that germ cell death is not required to mediate loss of Sertoli cells in BCLW-deficient mice. This suggests that Sertoli cells require BCLW in a cell-intrinsic manner for long-term survival. The loss of Sertoli cells in Bclw mutants commences shortly after Sertoli cells have become postmitotic. In situ hybridization analysis indicates that Bclw is expressed in Sertoli cells both before and after exit from mitosis. Therefore, Bclw-independent pathways promote the survival of undifferentiated, mitotic Sertoli cells. We show that BAX and BAK, two closely related death promoting members of the BCL2 family, are expressed in Sertoli cells. To determine whether either BAX or BAK activity is required for Sertoli cell death in Bclw mutant animals, we analyzed survival of Sertoli cells in Bclw/Bax and Bclw/Bak double homozygous mutant mice. While mutation of Bak had no effect, ablation of Bax suppressed the loss of Sertoli cells in Bclw mutants. Thus, BCLW mediates survival of postmitotic Sertoli cells in the mouse by suppressing death promoting activity of BAX. PMID- 11784037 TI - pasilla, the Drosophila homologue of the human Nova-1 and Nova-2 proteins, is required for normal secretion in the salivary gland. AB - From a screen for genes expressed and required in the Drosophila salivary gland, we identified pasilla (ps), which encodes a set of proteins most similar to human Nova-1 and Nova-2. Nova-1 and Nova-2 are nuclear RNA-binding proteins normally expressed in the CNS where they directly regulate splicing. In patients suffering from paraneoplastic opsoclonus myoclonus ataxia (POMA), Nova-1 and Nova-2 proteins are present as auto-antigens. Consistent with a role in splicing, PS is localized to nuclear puncta. The salivary glands of ps mutants internalize normally and maintain epithelial polarity. However, the mutant salivary glands develop irregularities in overall morphology and have defects in apical secretion. The secretory defects in ps mutants provide a potential mechanism for the loss of motor function observed in POMA patients. PMID- 11784038 TI - Embryonic origin of avian corneal sensory nerves. AB - Sensory nerves play a vital role in maintaining corneal transparency. They originate in the trigeminal ganglion, which is derived from two embryonic cell populations (cranial neural crest and ectodermal placode). Nonetheless, it is unclear whether corneal nerves arise from neural crest, from placode, or from both. Quail-chick chimeras and species-specific antibodies allowed tracing quail derived neural crest or placode cells during trigeminal ganglion and corneal development, and after ablation of either neural crest or placode. Neural crest chimeras showed quail nuclei in the proximal part of the trigeminal ganglion, and quail nerves in the pericorneal nerve ring and in the cornea. In sharp contrast, placode chimeras showed quail nuclei in the distal part of the trigeminal ganglion, but no quail nerves in the cornea or in the pericorneal nerve ring. Quail placode-derived nerves were present, however, in the eyelids. Neural crest ablation between stages 8 and 9 resulted in diminished trigeminal ganglia and absence of corneal innervation. Ablation of placode after stage 11 resulted in loss of the ophthalmic branch of the trigeminal ganglion and reduced corneal innervation. Noninnervated corneas still became transparent. These results indicate for the first time that although both neural crest and placode contribute to the trigeminal ganglion, corneal innervation is entirely neural crest-derived. Nonetheless, proper corneal innervation requires presence of both cell types in the embryonic trigeminal ganglion. Also, complete lack of innervation has no discernible effect on development of corneal transparency or cell densities. PMID- 11784039 TI - Overexpression of PDGF-A in the lung epithelium of transgenic mice produces a lethal phenotype associated with hyperplasia of mesenchymal cells. AB - Transgenic mice expressing platelet-derived growth factor A chain (PDGF-A) in the distal lung epithelium from the surfactant protein C (SPC) promoter were generated to investigate the role of this growth factor in lung development. Expression of the SPC-PDGFA transgene resulted in an enlarged, nonfunctional lung and perinatal lethality caused by failure to initiate ventilation. Histologic analysis of embryonic day (E) 16.5 lungs revealed increased mesenchymal cells and acinar buds and decreased bronchioles and dilated airspaces in SPC-PDGFA transgenic mice. At E18.5, nontransgenic lungs exhibited lung morphology typical of the saccular stage of lung development, including dilated airspaces, thin respiratory epithelium and mesenchyme, and elastin fiber deposition in primary septa. In contrast, E18.5 transgenic lungs retained many features of the canalicular stage of lung development, including undilated airspaces, cuboidal respiratory epithelium, thickened mesenchyme, and lack of parenchymal elastin deposition. These results indicate that PDGF-A is a potent growth factor for mesenchymal cells in the developing lung and that the downregulation of PDGF-A expression that normally occurs in the lung during late gestation is required for transition from the canalicular to the saccular stage of lung development. PMID- 11784040 TI - Coordination of ges-1 expression between the Caenorhabditis pharynx and intestine. AB - We have previously shown that the Caenorhabditis elegans gut-specific esterase gene (Ce-ges-1) has the unusual ability to be expressed in different modules of the embryonic digestive tract (anterior pharynx, posterior pharynx, and rectum) depending on sequence elements within the Ce-ges-1 promoter. In the present paper, we analyze the expression of the ges-1 homolog (Cb-ges-1) from the related nematode Caenorhabditis briggsae and show that Cb-ges-1 also has the ability to switch expression between gut and pharynx + rectum. The control of this expression switch centres on a tandem pair of WGATAR sites in the Cb-ges-1 5' flanking region, just as it does in Ce-ges-1. We use sequence alignments and subsequent deletions to identify a region at the 3'-end of both Ce-ges-1 and Ce ges-1 that acts as the ges-1 cryptic pharynx enhancer whose activity is revealed by removal of the 5' WGATAR sites. This region contains a conserved binding site for PHA-4 (the C. elegans ortholog of forkhead/HNF3 alpha, beta,gamma factors), which is expressed in all cells of the developing pharynx and a subset of cells of the developing rectum. We propose a model in which the normal expression of ges-1 is controlled by the gut-specific GATA factor ELT-2. We propose that, in the pharynx (and rectum), PHA-4 is normally bound to the ges-1 3'-enhancer sequence but that the activation function of PHA-4 is kept repressed by a (presently unknown) factor binding in the vicinity of the 5' WGATAR sites. We suggest that this control circuitry is maintained in Caenorhabditis because pharyngeal expression of ges-1 is advantageous only under certain developmental or environmental conditions. PMID- 11784041 TI - Displacement of the mitotic apparatus which induces ectopic polar body formation or parthenogenetic cleavage in starfish oocytes. AB - When the mitotic apparatus (MA) at meiosis I and II in starfish oocytes was detached from the animal pole and translocated to the other cortex, MA induced polar body formation, which indicates reattachment of MA to the cortex. MA attachment was so strong that MA at meiosis II was frequently broken into two parts during detachment and from the remnant part remaining at the cortex an aster derived and a nucleus derived from the detached part. When they were apart until the cleavage stage, the oocyte divided into the aster-containing and nucleus-containing blastomeres and, further, only the former blastomere divided repeatedly. This result indicates that the centrosome in the peripheral aster, which presumes to be discarded into the second polar body, always has the capacity of duplication but the centrosome in the inner aster, which stays in the oocyte interior, has not the capacity and confirms our previous report ( Saiki and Hamaguchi (1998) Dev. Biol. 203, 62-74). Furthermore, it is found by observing meiotic MA formation that this peculiar centrosome delivery at meiosis II is ensured by the fact that the attachment of the aster staying in the oocyte interior to the cortex occurs earlier than centrosome duplication. PMID- 11784042 TI - The major subacrosomal occupant of bull spermatozoa is a novel histone H2B variant associated with the forming acrosome during spermiogenesis. AB - Recent studies on the structural composition of mammalian sperm heads have shown a congregate of unidentified proteins occupying the periphery of the mammalian sperm nucleus, forming a layer of condensed cytosol. These proteins are the perinuclear theca (PT) and can be categorized into SDS-soluble and SDS-insoluble components. The present study focused on identifying the major SDS-insoluble PT protein, which we localized to the subacrosomal layer of bovine spermatozoa and cloned by immunoscreening a bull testicular cDNA library. The isolated clones encode a protein of 122 amino acids that bears 67% similarity with histone H2B and contains a predicted histone fold motif. The novel amino terminus of the protein contains a potential bipartite nuclear targeting sequence. Hence, we identified this prominent subacrosomal component as a novel H2B variant, SubH2Bv. Northern blot analyses of SubH2Bv mRNA expression showed that it is testis specific and is also present in murid testes. Immunocytochemical analysis showed SubH2Bv intimately associates, temporally and spatially, with acrosome formation. While the molecular features of SubH2Bv are common to nuclear proteins, it is never seen developmentally within the nucleus of the spermatid. Considering its developmental and molecular characteristics, we have postulated roles of SubH2Bv in acrosome assembly and acrosome-nuclear docking. PMID- 11784043 TI - Ion transport in sperm signaling. AB - Ion channels and transporters, key elements in sperm-egg signaling and environmental sensing, are essential for fertilization. External cues and components from the outer envelopes of the egg influence sperm ion permeability and behavior. Combining in vivo measurements of membrane potential, intracellular ions, and second messengers with new molecular approaches and reconstitution strategies are revealing how sperm ion channels participate in motility, sperm maturation, and the acrosome reaction. Sperm are tiny differentiated terminal cells unable to synthesize proteins and difficult to characterize electrophysiologically. Spermatogenic cells, the progenitors of sperm, have become useful tools for probing sperm ion channels since they are larger and molecular biology techniques can be applied. These complementary strategies are opening new avenues to determine how sperm ion channels function in gamete signaling. PMID- 11784044 TI - Hoxa3 regulates integration of glossopharyngeal nerve precursor cells. AB - In vertebrates, certain Hox genes are known to control cellular identities along the anterior-posterior (A-P) axis in the developing hindbrain. In mouse Hoxa3 mutants, truncation of the glossopharyngeal (IXth) nerve or the fusion of the IXth and vagus (Xth) nerves was reported, although its underlying mechanism is largely unknown. To elucidate the mechanism of the IXth nerve defects, we reexamined the phenotype of Hoxa3 mutant embryos. In Hoxa3 mutants, we observed an abnormal caudal stream of the migrating Hoxa3-expressing neural crest cells at the prospective IXth nerve-forming area. Dorsomedial migration of the placode derived neuronal precursor cells of the IXth nerve was also affected. Motor neurons at rhombomere 6 (r6), where those of the IXth nerve were positioned, often projected axons to the Xth nerve. In summary, the Hoxa3 gene has crucial roles in ensuring the correct axon projection pattern of all three components of the IXth nerve, i.e., motor neurons and sensory neurons of the proximal and distal ganglia. PMID- 11784045 TI - Hypodermal expression of Caenorhabditis elegans TGF-beta type I receptor SMA-6 is essential for the growth and maintenance of body length. AB - There are several transforming growth factor-beta (TGF-beta) pathways in the nematode Caenorhabditis elegans. One of these pathways regulates body length and is composed of the ligand DBL-1, serine/threonine protein kinase receptors SMA-6 and DAF-4, and cytoplasmic signaling components SMA-2, SMA-3, and SMA-4. To further examine the molecular mechanisms of body-length regulation in the nematode by the TGF-beta pathway, we examined the regional requirement for the type-I receptor SMA-6. Using a SMA-6::GFP (green fluorescent protein) reporter gene, sma-6 was highly expressed in the hypodermis, unlike the type-II receptor DAF-4, which is reported to be ubiquitously expressed. We then examined the ability of SMA-6 expression in different regions of the C. elegans body to rescue the sma-6 phenotype (small) and found that hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length. We also demonstrate that GATA sequences in the sma-6 promoter contribute to the hypodermal expression of sma-6. PMID- 11784046 TI - RARgamma and Cdx1 interactions in vertebral patterning. AB - Exogenous retinoic acid (RA) can evoke vertebral homeosis when administered during late gastrulation. These vertebral transformations correlate with alterations of the rostral limit of Hox gene expression in the prevertebrae, suggesting that retinoid signaling regulates the combinatorial expression of Hox genes dictating vertebral identity. Conversely, loss of certain RA receptors (RARs) results in anterior homeotic transformations principally affecting the cervical region. Despite these observations, the relationship between retinoid signaling, somitic Hox expression, and vertebral patterning is poorly understood. The members of the murine Cdx family (Cdx1, Cdx2, and Cdx4) are the homologues of Drosophila caudal and encode homeobox-containing transcription factors. Cdx1 homozygous null mutants exhibit anterior homeotic transformations, some of which are reminiscent of those in RARgamma null offspring. In Cdx1 mutants, these transformations occur concomitant with posteriorized prevertebral expression of certain Hox genes. Cdx1 has recently been demonstrated to be a direct RA target, suggesting an indirect means by which retinoid signaling may impact vertebral patterning. To further investigate this relationship, a complete allelic series of Cdx1-RARgamma mutants was generated and the skeletal phenotype assessed either following normal gestation or after administration of RA. Synergistic interactions between these null alleles were observed in compound mutants, and the full effects of exogenous RA on vertebral morphogenesis required Cdx1. These findings are consistent with a role for RA upstream of Cdx1 as regards axial patterning. However, exogenous RA attenuated several defects inherent to Cdx1 null mutants. This finding, together with the increased phenotypic severity of RARgamma-Cdx1 double null mutants relative to single nulls, suggests that these pathways also function in parallel, likely by converging on common targets. PMID- 11784047 TI - Formation of myocardium after the initial development of the linear heart tube. AB - Well after formation of the primary linear heart tube, the mesenchymal cardiac septa become largely myocardial, and myocardial sleeves are formed along the caval and pulmonary veins. This second wave of myocardium formation can be envisioned to be the result of recruitment of cardiomyocytes by differentiation from flanking mesenchyme and/or by migration from existing myocardium (myocardialization). As a first step to elucidate the underlying mechanism, we studied in chicken heart development the formation of myocardial cells within intra- and extracardiac mesenchymal structures. We show that the second wave of myocardium formation proceeds in a caudal-to-cranial gradient in vivo. At the venous pole, loosely arranged networks of cardiomyocytes are observed in the dorsal mesocardium from H/H19 onward, in the atrioventricular cushion region from H/H26 onward, and in the proximal outflow tract (conus) from H/H29 onward. The process is completed at H/H stage 43. Subsequently, we determined the potential of the different cardiac compartments to form myocardial networks in a 3D in vitro culture assay. This analysis showed that the competency to form myocardial networks in vitro is a characteristic of the myocardium that is flanked by intra- or extracardiac mesenchyme, i.e., the inflow tract, atrioventricular canal, and outflow tract. These cardiac compartments can be induced to form myocardial networks by a temporally released or secreted signal that is similar throughout the entire heart. Atrial and ventricular compartments are not competent and do not produce the inducer. Moreover, cardiac cushion mesenchyme was found to be able to (trans-)differentiate into cardiomyocytes in the in vitro culture assay. The combined observations suggest that a common mechanism and molecular regulatory pathway underlies the recruitment of mesodermal cells into the cardiogenic lineage during this second wave of myocardium formation through the entire heart. PMID- 11784048 TI - Transcription factors of the anterior neural plate alter cell movements of epidermal progenitors to specify a retinal fate. AB - The embryonic progenitors that give rise to the vertebrate retina acquire their cell fate identity through a series of transitions that ultimately determine their final, differentiated retinal cell fates. In Xenopus, these transitions have been broadly defined as competence, specification, and determination. The expression of several transcription factors within the anterior neural plate at the time when the presumptive eye field separates from other neural derivatives suggests that these genes function to specify competent embryonic progenitors toward a retinal fate. In support of this, we demonstrate that some transcription factors expressed in the anterior neural ectoderm and/or presumptive eye field (otx2, pax6, and rx1) change the fate of competent, ventral progenitors, which normally do not contribute to the retina, from an epidermal to a retinal fate. Furthermore, the expression of these factors changes the morphogenetic movements of progenitors during gastrulation, causing ventral cells to populate the native anterior neural plate. In addition, we experimentally demonstrate that the efficacy of pax6 to specify retinal cells depends on the position of the affected cell relative to the field of neural induction. Thereby, otx2, pax6, and rx1 mediate early steps of retinal specification, including the regulation of morphogenetic cell movements, that are dependent on the level of neural-inductive signaling. PMID- 11784049 TI - Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor. AB - The expression of Sry in the undifferentiated, bipotential genital ridges of mammalian XY fetuses initiates testis development and is hypothesized to do so by directing supporting cell precursors to develop as Sertoli cells and not as granulosa cells. To directly test this hypothesis, transgenic mice expressing EGFP under the control of the Sry promoter were produced. After establishing that the transgene was expressed in fetal gonads similarly to endogenous Sry, the spatial and temporal expression of the Sry-EGFP transgene was investigated in developing gonads by using confocal microscopy and immunofluorescent histochemistry. This analysis indicated: (1) Sry is first expressed in cells located centrally in the genital ridge and then later in cells located at the cranial and caudal poles, (2) Sry is expressed exclusively in pre-Sertoli cells in the urogenital ridge, and (3) Sertoli and granulosa cells develop from a common precursor. These results support the hypothesis that Sry initiates testis differentiation by directing the development of supporting cell precursors as Sertoli rather than granulosa cells. Furthermore, the Sry expression pattern explains the nonrandom distribution of testicular and ovarian tissue in mammalian ovotestes. PMID- 11784050 TI - Mechanisms of mesendoderm internalization in the Xenopus gastrula: lessons from the ventral side. AB - Two main processes are involved in driving ventral mesendoderm internalization in the Xenopus gastrula. First, vegetal rotation, an active movement of the vegetal cell mass, initiates gastrulation by rolling the peripheral blastocoel floor against the blastocoel roof. In this way, the leading edge of the internalized mesendoderm is established, that remains separated from the blastocoel roof by Brachet's cleft. Second, in a process of active involution, blastopore lip cells translocate on arc-like trails around the tip of Brachet's cleft. Hereby the lower, Xbra-negative part of the lip moves toward the interior, to contribute mainly to endoderm. In contrast, the upper, Xbra-expressing part moves toward the blastocoel roof-apposed surface of the involuted mesoderm, and eventually becomes inserted into this surface. Vegetal rotation and active mesoderm surface insertion persist over much of gastrulation ventrally. Both processes are also active dorsally. In fact, internalization processes generally spread from dorsal to ventral, though at different rates, which suggests that they are independently controlled. Ventrally and laterally, mesoderm occurs not only in the marginal zone, but also in the adjacent blastocoel roof. Such blastocoel roof mesoderm shares properties with the remaining, ectodermal roof, that are related to its function as substratum for mesendoderm migration. It repels involuted mesoderm, thus contributing to separation of cell layers, and it assembles a fibronectin matrix. These properties change as the blastocoel roof mesoderm moves into the blastopore lip during gastrulation. PMID- 11784051 TI - Apoptosis in the developing zebrafish embryo. AB - Apoptosis is a major part of the normal development of many organ systems and tissues. The zebrafish (Danio rerio) has become a useful model for studying early development, and recent advances in techniques used to label apoptotic cells have made it possible to visualize apoptotic cells in this model system. We have used the in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) to describe the temporal and spatial distribution of apoptotic cells during normal development of the zebrafish embryo from 12 to 96 h postfertilization. By counting labeled apoptotic cells, we have demonstrated transient high rates of cell death in various structures during development, and we have correlated these peaks with previously described developmental changes in these structures. Our analysis has focused on the nervous system and associated sensory organs including the olfactory organ, retina, lens, cornea, otic vesicle, lateral line organs, and Rohon-Beard neurons. Apoptosis is also described in other non-neural structures such as the notochord, somites, muscle, tailbud, and fins. PMID- 11784052 TI - Functional nicotinic acetylcholine receptor expression in stem and progenitor cells of the early embryonic mouse cerebral cortex. AB - The adult cerebral cortex contains nicotinic acetylcholine (ACh) receptors vital to cortical function. However, little is known about the assembly of embryonic nicotinic receptor subunits into functional receptors or whether they play an active role in cortical development. We now report evidence of functional nicotinic acetylcholine receptor channels in fetal mouse cerebral cortex as early as embryonic day 10 (E10), when the cortex consists of dividing stem and progenitor cells. Patch-clamp electrophysiological measurements indicate that nicotine and ACh evoke sizable inward currents characteristic of nicotinic receptors, that are strongly rectifying with a reversal potential near 0 mV. Three different nicotinic agonists, ACh, nicotine, and dimethylphenylpiperazinium, evoked cytosolic Ca(2+) signals. Agonist-evoked Ca(2+) signals and electrophysiological responses were found in greater than 70% of all E10-E11 cells tested and were blocked by nicotinic receptor antagonists. The Ca(2+) response to nicotinic agonists was markedly prolonged in cells from early embryonic stages relative to later stages of development. alpha3, alpha4, and alpha7 receptor subunit proteins were detected immunocytochemically in cortical cells from E10 to birth. The incidence of each subunit declined with embryonic age, suggesting a role in early development. We discuss the possible function of nicotinic receptors in early cortical development and their role as a target for nicotine in the developmental pathologies associated with the fetal tobacco syndrome. PMID- 11784053 TI - Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. AB - The Smad family of intracellular signaling intermediates transduce signals downstream from the transforming growth factor beta (TGF-beta) family of receptor serine threonine kinases. The original member of this family, Smad1, has been shown to mediate signals from receptors for the bone morphogenetic proteins (BMPs), a large group of ligands in the TGF-beta superfamily that mediate important developmental events. We have targeted the Smad1 gene in mice and created mutants null at this locus. Smad1 mutant mice die at approximately 9.5 days postcoitum due to defects in allantois formation. In Smad1 mutant mice, the allantois fails to fuse to the chorion, resulting in a lack of placenta and failure to establish a definitive embryonic circulation. Although vasculogenesis is initiated in the mutant allantois, the vessels formed are disorganized, and VCAM-1 protein, a marker for distal allantois development, is not expressed. Smad1 null fibroblasts are still able to respond to BMP2, however, suggesting that the defect observed in the developing extraembryonic tissue is caused by a very specific loss of transcriptional activity regulated by Smad1. Our data further demonstrate that although highly similar structurally, Smad proteins are not functionally homologous. PMID- 11784054 TI - MAP kinase converts MyoD into an instructive muscle differentiation factor in Xenopus. AB - In amphibian development, muscle is specified in the dorsal lateral marginal zone (DLMZ) of the gastrula embryo. Two critical events specify the formation of skeletal muscle: the expression of the myogenic transcription factor, XMyoD, and the secretion of bone morphogenetic protein (BMP) antagonists by the adjacent Spemann organizer. Inhibition of BMP signaling during early gastrula stages converts XMyoD protein into an instructive differentiation factor in the DLMZ. Yet, the intracellular signaling factors connecting BMP antagonism and activation of XMyoD remain unknown. Our data show that BMP antagonism induces the activity of mitogen-activated protein kinase (MAPK), and that the activity of MAPK is necessary for muscle-specific differentiation. Treatment of gastrula-stage DLMZ explants with MAPK pathway inhibitors ventralized mesoderm and prevented muscle differentiation. Expression of XMyoD in ventral mesoderm weakly induced muscle formation; however, the coexpression of a constitutively active MEK1 with XMyoD efficiently induced muscle differentiation. Activation of the MAPK pathway did not induce the transcription of XMyoD, but increased its protein levels and transcriptional activity. Thus, MAPK activation is subsequent to BMP antagonism, and participates in the dorsalization of mesoderm by converting the XMyoD protein into a potent differentiation factor. PMID- 11784055 TI - Exogenous amino acids regulate trophectoderm differentiation in the mouse blastocyst through an mTOR-dependent pathway. AB - At the late blastocyst stage, the epithelial trophectoderm cells of the mammalian embryo undergo a phenotypic change that allows them to invade into the uterine stroma and make contact with the maternal circulation. This step can be regulated in vitro by the availability of amino acids. Embryos cultured in defined medium lacking amino acids cannot form trophoblast cell outgrowths on fibronectin, an in vitro model of implantation, but remain viable for up to 3 days in culture and will form outgrowths when transferred into complete medium. The amino acid requirement is a developmentally regulated permissive event that occurs during a 4- to 8-h period at the early blastocyst stage. Amino acids affect spreading competence specifically by regulating the onset of protrusive activity and not the onset of integrin activation. Rapamycin, a specific inhibitor of the kinase mTOR/FRAP/RAFT1, blocks amino acid stimulation of embryo outgrowth, demonstrating that mTOR is required for the initiation of trophectoderm protrusive activity. Inhibition of global protein translation with cycloheximide also inhibits amino acid-dependent signals, suggesting that mTOR regulates the translation of proteins required for trophoblast differentiation. Our data suggest that mTOR activity has a developmental regulatory function in trophectoderm differentiation that may serve to coordinate embryo and uterus at the time of implantation. PMID- 11784056 TI - Epithelial-stromal tissue interaction in paramesonephric (Mullerian) epithelial differentiation. AB - During organogenesis, the middle to caudal portion of Mullerian epithelium differentiates into uterine and vaginal epithelia in females. Functional differentiation of uterine and vaginal epithelia occurs in adulthood, and is regulated by 17beta-estradiol (E(2)) and progesterone. In this report, the roles of mesenchyme/stroma in differentiation of uterine and vaginal epithelia were studied in tissue recombination experiments. At birth, Mullerian epithelium was negative for uterine and vaginal epithelial markers. Tissue recombinant experiments showed that uterine and vaginal gene expression patterns were induced in neonatal Mullerian epithelium by the respective mesenchymes. Differentiated adult uterine and vaginal epithelia did not change their original gene expression in response to heterotypic mesenchymal induction. In the adult vagina, E(2) induced expression of involucrin, a CCAAT/enhancer-binding protein beta and cytokeratin 1 via estrogen receptor alpha (ERalpha). Tissue recombination experiments with wild-type and ERalpha knockout mice demonstrated that epithelial gene expression is regulated by E(2) via epithelial-stromal tissue interactions. Uterine/vaginal heterotypic tissue recombinations demonstrated that functional differentiation of uterine and vaginal epithelia required organ-specific stromal factors. In contrast, stromal signals regulating epithelial proliferation appeared to be nonspecific in the uterus and vagina. PMID- 11784057 TI - Mutation in Bmp7 exacerbates the phenotype of Bmp8a mutants in spermatogenesis and epididymis. AB - The specificity of bone morphogenetic proteins (BMPs) to their putative heteromeric receptor complexes in vivo is largely unclear. Closely related BMPs may use the same or different receptor complexes for signaling in a time- and space-dependent manner during development and differentiation. We have shown that Bmp7 expression in epididymal epithelium is developmentally regulated. Here, we further show that Bmp7 expression is also developmentally regulated in male germ cells. Bmp7 transcripts are detected in spermatogonia and early primary spermatocytes during early puberty and in stage-7 to -15 spermatids of the adult mice. Since Bmp7 homozygous mutants die perinatally and heterozygotes do not show obvious defects in the testis and the epididymis, the role of Bmp7 in spermatogenesis and epididymal function cannot be revealed by simply examining these mutants. Therefore, we have used a genetic approach by creating Bmp7/Bmp8a double mutants to investigate the role of Bmp7 in spermatogenesis and epididymal function. Here, we report that removal of one allele of Bmp7 exacerbates the phenotype of Bmp8a null mutants in spermatogenesis and epididymis of the adult. These indicate that, similar to Bmp8a, Bmp7 plays a role in both the maintenance of spermatogenesis and epididymal function and it further suggests that BMP8 and BMP7 signal through the same or similar receptors in these two systems. PMID- 11784058 TI - otx2 expression in the ectoderm activates anterior neural determination and is required for Xenopus cement gland formation. AB - We previously showed that otx2 regulates Xenopus cement gland formation in the ectoderm. Here, we show that otx2 is sufficient to direct anterior neural gene expression, and that its activity is required for cement gland and anterior neural determination. otx2 activity at midgastrula activates anterior and prevents expression of posterior and ventral gene expression in whole embryos and ectodermal explants. These data suggest that part of the mechanism by which otx2 promotes anterior determination involves repression of posterior and ventral fates. A dominant negative otx2-engrailed repressor fusion protein (otx2-En) ablates endogenous cement gland formation, and inhibits expression of the mid/hindbrain boundary marker engrailed-2. Ectoderm expressing otx2-En is not able to respond to signals from the mesoderm to form cement gland, and is impaired in its ability to form anterior neural tissue. These results compliment analyses in otx2 mutant mice, indicating a role for otx2 in the ectoderm during anterior neural patterning. PMID- 11784059 TI - Efficient gene transfer into the embryonic mouse brain using in vivo electroporation. AB - Mouse genetic manipulation has provided an excellent system to characterize gene function in numerous contexts. A number of mutants have been produced by using transgenic, gene knockout, and mutagenesis techniques. Nevertheless, one limitation is that it is difficult to express a gene in vivo in a restricted manner (i.e., spatially and temporally), because the number of available enhancers and promoters which can confine gene expression is limited. We have developed a novel method to introduce DNA into in/exo utero embryonic mouse brains at various stages by using electroporation. More than 90% of operated embryos survived, and more than 65% of these expressed the introduced genes in restricted regions of the brain. Expression was maintained even after birth, 6 weeks after electroporation. The use of fluorescent protein genes clearly visualized neuronal morphologies in the brain. Moreover, it was possible to transfect three different DNA vectors into the same cells. Thus, this method will be a powerful tool to characterize gene function in various settings due to its high efficiency and localized gene expression. PMID- 11784060 TI - Persistent expression of Hlxb9 in the pancreatic epithelium impairs pancreatic development. AB - The homebox gene Hlxb9, encoding Hb9, exhibits a dual expression profile during pancreatic development. The early expression in the dorsal and ventral pancreatic epithelium is transient and spans from embryonic day (e) 8 to e9-e10, whereas the later expression is confined to differentiating beta-cells as they appear. We previously showed that Hlxb9 is critically required for the initiation of the dorsal, but not the ventral, pancreatic program. Here, we demonstrate the requirement for a stringent temporal regulation of Hlxb9 expression during early stages of pancreatic development. In transgenic mice, where Hlxb9 expression, under control of the Ipf1/Pdx1 promoter, was extended beyond e9-e10, the development of the pancreas was drastically perturbed. Morphological analyses showed that the growth and morphogenesis of the pancreatic epithelium was impaired. Moreover, differentiation of pancreatic endocrine and exocrine cells was diminished and instead the pancreatic epithelium with its adjacent mesenchyme adopted an intestinal-like differentiation program. Together, these data point to a need for a tight temporal regulation of Hlxb9 expression. Thus, a total loss of Hlxb9 expression results in a block of the initiation of the dorsal pancreatic program, while a temporally extended expression of Hlxb9 results in a complete impairment of pancreatic development. PMID- 11784061 TI - Calmegin is required for fertilin alpha/beta heterodimerization and sperm fertility. AB - Loss of the endoplasmic reticulum resident chaperone calmegin leads to the production of sterile sperm that do not bind to the egg zona pellucida (M. Ikawa et al., 1997, Nature 387, 607-611). In the present study, we demonstrate that calmegin -/- sperm were defective in migrating into the oviducts and in binding to the egg plasma membrane. Despite the impaired adhesive function, calmegin -/- sperm could fertilize eggs when zonae pellucidae were partially dissected, and eggs fertilized in this manner could develop normally to term. Since these sperm characteristics were similar to those found in fertilin beta -/- sperm, we investigated the interaction of calmegin with fertilin beta. Using immunoprecipitation techniques, calmegin was found to bind to sperm membrane proteins, fertilin alpha and beta, during spermatogenesis. The binding was specific to calmegin: another endoplasmic reticulum chaperone calnexin, a calmegin homologue, was not able to bind to fertilin alpha and beta. In the calmegin -/- mice, a loss of heterodimerization of fertilin alpha and beta was observed and fertilin beta was not detectable in mature sperm. The data not only explain why the calmegin and fertilin beta knockout mouse lines share a common infertile phenotype, but also reveal the importance of the maturation of sperm membrane proteins in the endoplasmic reticulum. PMID- 11784062 TI - Three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) associated with the tail bud: the evolution of somitogenesis in chordates. AB - The amphioxus tail bud is similar to the amphibian tail bud in having an epithelial organization without a mesenchymal component. We characterize three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) and show that their early expression around the blastopore can subsequently be traced into the tail bud; in vertebrate embryos, there is a similar progression of expression domains for Wnt3, Wnt5, and Wnt6 genes from the blastopore lip (or its equivalent) to the tail bud. In amphioxus, AmphiWnt3, AmphiWnt5, and AmphiWnt6 are each expressed in a specific subregion of the tail bud, tentatively suggesting that a combinatorial code of developmental gene expression may help generate specific tissues during posterior elongation and somitogenesis. In spite of similarities within their tail buds, vertebrate and amphioxus embryos differ markedly in the relation between the tail bud and the nascent somites: vertebrates have a relatively extensive zone of unsegmented mesenchyme (i.e., presomitic mesoderm) intervening between the tail bud and the forming somites, whereas the amphioxus tail bud gives rise to new somites directly. It is likely that presomitic mesoderm is a vertebrate innovation made possible by developmental interconversions between epithelium and mesenchyme that first became prominent at the dawn of vertebrate evolution. PMID- 11784063 TI - Apoptosis is required for the proper formation of the ventriculo-arterial connections. AB - The role of apoptosis in cardiac morphogenesis has not been directly tested. Cardiomyocyte apoptosis is prevalent during the remodeling of the embryonic chicken cardiac outflow tract (OFT) in the transition from a single to a dual circulation. We tested the hypothesis that OFT cardiomyocyte apoptosis drives the shortening and rotation of the embryonic cardiac OFT and is required to achieve the mature ventriculo-arterial configuration. Chick embryos were treated with the peptide Caspase inhibitors zVAD-fmk or DEVD-cho at HH stages 15-20 (looped heart). Morphology of control and experimental embryos was assessed at HH stage 35, at which time the control hearts have developed a dual circulation. Infection of the hearts with a recombinant adenovirus expressing green fluorescent protein was used to follow the fate of the OFT cardiomyocytes. Affected embryos displayed abnormal persistence of a long infundibulum (OFT myocardial remnant) beneath the great vessels, indicating failure of OFT shortening. In some instances, the infundibulum connected both great vessels to the right ventricle in a side-by side arrangement with transposition of the aorta, indicating a failure of rotation of the OFT, and modeling human congenital double outlet right ventricle. Defects were also observed at other sites in the heart where apoptosis is prevalent, such as in the formation of the cardiac valves and trabeculae. To more specifically target the apoptosis of the OFT cardiomyocytes, recombinant adenovirus was used to express the X-linked inhibitor of apoptosis protein in these cells. This resulted in an effect on outflow tract shortening and rotation similar to that of the peptide inhibitors, while the effects on the other cardiac structures were not observed. These results demonstrate that elimination of OFT cardiomyocytes by apoptosis is necessary for the proper formation of the ventriculo-arterial connections, and suggest apoptosis as a potential target of teratogens and genetic defects that are associated with congenital human conal heart defects. PMID- 11784064 TI - Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation. AB - Oocytes secrete soluble factors that regulate the growth and differentiation of follicular cells, including maintenance of the distinctive cumulus cell phenotype. This study determines whether the mitogenic activity of oocytes is developmentally regulated and examines the responsiveness of follicular cells to oocytes at different stages of follicular development. Prepubertal SV129 mice of varying ages were primed with 5 IU equine chorionic gonadotropin (eCG) and oocytes/zygotes collected either 46 h post-eCG (immature oocytes), 12 h after administration of 5 IU human CG (hCG; ovulated ova), or 12 h post-hCG and mating (zygotes). Mural granulosa cells (MGC) from antral follicles and GC from preantral follicles were cultured +/- denuded oocytes (DO) for 18 h, followed by a 6-h pulse of [(3)H]thymidine as an indicator of cellular DNA synthesis. Coculturing MGC with meiotically maturing oocytes led to a dose-dependent increase in [(3)H]thymidine incorporation (20-fold above control levels at 0.5 DO/microl). However, [(3)H] counts remained unchanged from control levels when cultured with meiotically incompetent DO from 11- to 15-day-old mice (3% germinal vesicle breakdown; GVB), irrespective of dose of DO or developmental status of GC (MGC or preantral GC). In some treatments, spontaneous meiotic resumption of competent oocytes was prevented by culturing with 5 microM milrinone, a selective inhibitor of oocyte-specific cyclic nucleotide phosphodiesterase. The mitogenic capacity of oocytes was found to decline during and after oocyte maturation. [(3)H]Thymidine incorporation in MGC was highest (11-fold above controls) when cultured with meiotically inhibited (milrinone-treated) GV DO, stimulated 5.5 fold by culture with maturing oocytes, 3-fold with ovulated ova, and unstimulated by zygotes. [(3)H]Thymidine incorporation in MGC was not altered by the dose of milrinone, either in the presence or absence of DO. Metaphase I marked the beginning of the decline in the capacity of oocytes to promote MGC DNA synthesis. These results demonstrate that the capacity of oocytes to promote proliferation of granulosa cells follows a developmental program, closely linked to oocyte meiotic status, increasing with the acquisition of meiotic competence and declining during and after oocyte maturation. PMID- 11784065 TI - How the zebrafish gets its stripes. AB - The study of vertebrate pigment patterns is a classic and enduring field of developmental biology. Knowledge of pigment pattern development comes from a variety of systems, including avians, mouse, and more recently, the zebrafish (Danio rerio). Recent analyses of the mechanisms underlying the development of the neural crest-derived pigment cell type common to all vertebrates, the melanocyte, have revealed remarkable similarities and several surprising differences between amniotes and zebrafish. Here, we summarize recent advances in the study of melanocyte development in zebrafish, with reference to human, mouse, and avian systems. We first review melanocyte development in zebrafish and mammals, followed by a summary of the molecules known to be required for their development. We then discuss several relatively unaddressed issues in vertebrate pigment pattern development that are being investigated in zebrafish. These include determining the relationships between genetically distinct classes of melanocytes, characterizing and dissecting melanocyte stem cell development, and understanding how pigment cells organize into a patterned tissue. Further analysis of zebrafish pigment pattern mutants as well as new generations of directed mutant screens promise to extend our understanding of pigment pattern morphogenesis. PMID- 11784066 TI - Perturbing nuclear transport in Drosophila eye imaginal discs causes specific cell adhesion and axon guidance defects. AB - To study nucleocytoplasmic transport during multicellular development, we developed a sensitive nuclear protein import assay in living blastoderm embryos. We show that dominant negative truncations of the human nuclear transport receptor karyopherinbeta/Importinbeta (DNImpbeta) disrupt mRNA export and protein import in Drosophila. To test the sensitivity of different developmental processes to nuclear trafficking perturbations, we expressed DNImpbeta behind the morphogenetic furrow of the eye disc, at a time when photoreceptors are patterned and project their axons to the brain. DNImpbeta expression does not disrupt the correct specification of different photoreceptors, but causes a defect in cell adhesion that leads to some photoreceptors descending below the layer of ommatidia. The photoreceptors initially project their axons correctly to the posterior, but later their axons are unable to enter the optic stalk en route to the brain and continue to project an extensive network of misguided axons. The axon guidance and cell adhesion defects are both due to a disruption in the function of Ketel, the Drosophila ortholog of Importinbeta. We conclude that cell adhesion and axon guidance in the eye have specific requirements for nucleocytoplasmic transport, despite involving processes that occur primarily at the cell surface. PMID- 11784067 TI - Neuron-glia communication via nitric oxide is essential in establishing antennal lobe structure in Manduca sexta. AB - Nitric oxide synthase recently has been shown to be present in olfactory receptor cells throughout development of the adult antennal (olfactory) lobe of the brain of the moth Manduca sexta. Here, we investigate the possible involvement of nitric oxide (NO) in antennal-lobe morphogenesis. Inhibition of NO signaling with a NO synthase inhibitor or a NO scavenger early in development results in abnormal antennal lobes in which neuropil-associated glia fail to migrate. A more subtle effect is seen in the arborization of dendrites of a serotonin immunoreactive neuron, which grow beyond their normal range. The effects of NO signaling in these types of cells do not appear to be mediated by activation of soluble guanylyl cyclase to produce cGMP, as these cells do not exhibit cGMP immunoreactivity following NO stimulation and are not affected by infusion of a soluble guanylyl cyclase inhibitor. Treatment with Novobiocin, which blocks ADP ribosylation of proteins, results in a phenotype similar to those seen with blockade of NO signaling. Thus, axons of olfactory receptor cells appear to trigger glial cell migration and limit arborization of serotonin-immunoreactive neurons via NO signaling. The NO effect may be mediated in part by ADP ribosylation of target cell proteins. PMID- 11784068 TI - The secreted glycoprotein Noelin-1 promotes neurogenesis in Xenopus. AB - Neurogenesis in Xenopus neural ectoderm involves multiple gene families, including basic helix-loop-helix transcription factors, which initiate and control primary neurogenesis. Equally important, though less well understood, are the downstream effectors of the activity of these transcription factors. We have investigated the role of a candidate downstream effector, Noelin-1, during Xenopus development. Noelin-1 is a secreted glycoprotein that likely forms large multiunit complexes. In avians, overexpression of Noelin-1 causes prolonged and excessive neural crest migration. Our studies in Xenopus reveal that this gene, while highly conserved in sequence, has a divergent function in primary neurogenesis. Xenopus Noelin-1 is expressed mainly by postmitotic neurogenic tissues in the developing central and peripheral nervous systems, first appearing after neural tube closure. Its expression is upregulated in ectopic locations upon overexpression of the neurogenic genes X-ngnr-1 and XNeuroD. Noelin-1 expression in animal caps induces expression of neural markers XBrn-3d and XNeuroD, and co-expression of secreted Noelin-1 with noggin amplifies noggin induced expression of XBrn-3d and XNeuroD. Furthermore, in animal caps neuralized by expression of noggin, co-expression of Noelin-1 causes expression of neuronal differentiation markers several stages before neurogenesis normally occurs in this tissue. Finally, only secreted forms of the protein can activate sensory marker expression, while all forms of the protein can induce early neurogenesis. This suggests that the cellular localization of Noelin-1 may be important to its function. Thus, Noelin-1 represents a novel secreted factor involved in neurogenesis. PMID- 11784069 TI - scabrous modifies epithelial cell adhesion and extends the range of lateral signalling during development of the spaced bristle pattern in Drosophila. AB - The role of scabrous (sca) in the evenly spaced bristle pattern of Drosophila is explored. Loss-of-function of sca results in development of an excess of bristles. Segregation of alternately spaced bristle precursors and epidermal cells from a group of equipotential cells relies on lateral inhibition mediated by Notch and Delta (Dl). In this process, presumptive bristle precursors inhibit the neural fate of neighbouring cells, causing them to adopt the epidermal fate. We show that Dl, a membrane-bound ligand for Notch, can inhibit adjacent cells, in direct contact with the precursor, in the absence of Sca. In contrast, inhibition of cells not adjacent to the precursor requires, in addition, Sca, a secreted molecule with a fibrinogen-related domain. Over-expression of Sca in a wild-type background, leads to increased spacing between bristles, suggesting that the range of signalling has been increased. scabrous acts nonautonomously, and we present evidence that, during bristle precursor segregation, Sca is required to maintain the normal adhesive properties of epithelial cells. The possible effects of such changes on the range of signalling are discussed. We also show that the sensory organ precursors extend numerous fine cytoplasmic extensions bearing Dl molecules, and speculate on a possible role for these structures during signalling. PMID- 11784070 TI - Vegetal localization of maternal mRNAs is disrupted by VegT depletion. AB - VegT is an essential maternal regulator of germ layer specification in Xenopus. The localization of VegT mRNA to the vegetal cortex of the oocyte during oogenesis ensures its inheritance by vegetal and not animal cells, and directs the differentiation of vegetal cells into endoderm. Similarly localized mRNAs, Vg1 and Bicaudal-C, are also inherited by vegetal cells, while germ plasm associated mRNAs, such as Xcat2, become incorporated into vegetally derived primordial germ cells. Although mRNA localization is clearly important for tissue specification, the mechanism of mRNA anchoring to the oocyte vegetal cortex is not understood. Here, we examine the role of VegT in cortical localization. We report that depletion of VegT mRNA caused the release of Vg1 mRNA from the vegetal cortex and a reduction of Vg1 protein, without affecting the total amount of Vg1 transcript. Furthermore, we found that Bicaudal-C and Wnt11 mRNAs were also dispersed, but not degraded, by VegT depletion, while the localization of Xcat2 and Xotx1 mRNAs was unaffected. This effect was specific to the loss of VegT mRNA and not VegT protein, since a morpholino oligo against VegT, that blocked translation without degrading mRNA, did not disperse the vegetally localized mRNAs. Therefore, a subset of localized mRNAs is dependent on VegT mRNA for anchoring to the vegetal cortex, indicating a novel function for maternal VegT mRNA. PMID- 11784071 TI - Dorsoventral differences in cell-cell interactions modulate the motile behaviour of cells from the Xenopus gastrula. AB - When groups of cells from the inner marginal zone (mesendoderm) of the early Xenopus gastrula are placed on a fibronectin-coated substratum, the explants of the dorsal region spread into monolayers whereas those from the ventral region, though they adhere to the substratum, do not show this spreading reaction. This different behaviour is not reflected in the in vitro behaviour of the respective cells kept in isolation. No difference between dorsal and ventral cells was observed, when they were tested for lamellipodia-driven spreading, movement over the substratum or properties of integrin- and cadherin-mediated adhesion. However, cell contacts between individual dorsal cells are significantly less stable than those between ventral cells. The higher flexibility of the cell-cell contacts seems to determine the spreading behaviour of the dorsal explants, which includes lamellipodia-driven outward movement of the peripheral cells, rearrangements of the cells, building up a horizontal tension within the aggregate and intercalation of cells from above into the bottom layer. Ventral explants lack these properties. Staining for F-actin revealed a decisive difference of the supracellular organisation of the cytoskeleton that underlies the morphology of the different types of explants. Evidence for a higher flexibility of cell-cell contacts in the dorsal mesendoderm was also obtained in SEM studies on gastrulating embryos. Dorsal mesendodermal cells show stronger protrusive activity as compared to ventral mesendodermal cells. The meaning of these observations for the mechanisms of morphogenetic movements during gastrulation is central to the discussion. PMID- 11784072 TI - Coronary smooth muscle differentiation from proepicardial cells requires rhoA mediated actin reorganization and p160 rho-kinase activity. AB - We recently reported that the first detectable expression of SMC-specific proteins during coronary smooth muscle cell (CoSMC) differentiation from isolated proepicardial cells was restricted to cells undergoing epithelial-to-mesenchymal transformation (EMT). The objectives of this study were to examine more closely the relation between actin cytoskeletal rearrangements and serum response factor (SRF)-dependent transcription, and to specifically test whether rhoA-GTPase signaling is required for CoSMC differentiation. We report here that PDGF-BB stimulates EMT and promotes SRF-dependent expression of SMC marker genes calponin, SM22alpha, and SMgamma(actin) (SMgammaA) in proepicardial cells. C3 exoenzyme or rhoGDI, inhibitors of rhoA signaling, blocked PDGF-BB-induced EMT, prevented actin reorganization into stress fibers, and inhibited CoSMC differentiation. Incubation with the selective p160 rho-kinase (p160RhoK) inhibitor Y27632 (RKI) blocked EMT, prevented the appearance of calponin and SMgammaA-positive cells, and abolished expression and nuclear localization of SRF. To test the role of RhoK signaling for CoSMC differentiation in vivo, quail proepicardial organs (PEOs) were pretreated with RKI or vehicle and then grafted into age-matched host chick embryos to produce a chimeric epicardium. The ability of grafted cells to participate in coronary vessel formation was monitored by staining with antibodies for quail cell nuclear antigen and SMC marker proteins. Proepicardial cells pretreated with RKI failed to form CoSMCs in vivo. Time course studies traced this deficiency to a failure of epicardial-derived mesenchymal cells to migrate into or survive within the myocardium. In summary, these data point to important roles for rhoA-RhoK signaling in molecular pathways controlling cytoskeletal reorganization, SRF-dependent transcription, and cell survival that are required to produce CoSMCs from proepicardial cells. PMID- 11784073 TI - TGFbeta2 in corneal morphogenesis during mouse embryonic development. AB - To examine the roles of TGFbeta isoforms on corneal morphogenesis, the eyes of mice that lack TGFbetas were analyzed at different developmental stages for cell proliferation, migration and apoptosis, and for expression patterns of keratin 12, lumican, keratocan and collagen I. Among the three Tgfb(-/-) mice, only Tgfb2(-/-) mice have abnormal ocular morphogenesis characterized by thin corneal stroma, absence of corneal endothelium, fusion of cornea to lens (a Peters'-like anomaly phenotype), and accumulation of hyaline cells in vitreous. In Tgfb2(-/-) mice, fewer keratocytes were found in stroma that has a decreased accumulation of ECM; for example, lumican, keratocan and collagen I were greatly diminished. The absence of TGFbeta2 did not compromise cell proliferation, nor enhance apoptosis. The thinner stroma resulting from decreased ECM synthesis may account for the decreased cell number in the stroma of Tgfb2 null mice. Keratin 12 expression was not altered in Tgfb2(-/-) mice, implicating normal corneal type epithelial differentiation. Delayed appearance of macrophages in ocular tissues was observed in Tgfb2(-/-) mice. Malfunctioning macrophages may account for accumulation of cell mass in vitreous of Tgfb2 null mice. PMID- 11784074 TI - Regulation of endochondral cartilage growth in the developing avian limb: cooperative involvement of perichondrium and periosteum. AB - The perichondrium and periosteum have recently been suggested to be involved in the regulation of limb growth, serving as potential sources of signaling molecules that are involved in chondrocyte proliferation, maturation, and hypertrophy. Previously, we observed that removal of the perichondrium and periosteum from tibiotarsi in organ culture resulted in an overall increase in longitudinal cartilage growth, suggesting negative regulation originating from these tissues. To determine if the perichondrium and periosteum regulate growth through the production of diffusible factors, we have tested various conditioned media from these tissues for the ability to modify cartilage growth in tibiotarsal organ cultures from which these tissues have been removed. Both negative and positive regulatory activities were detected. Negative regulation was observed with conditioned medium from (1) cell cultures of the region bordering both the perichondrium and the periosteum, (2) co-cultures of perichondrial and periosteal cells, and (3) a mixture of conditioned media from perichondrial cell cultures and periosteal cell cultures. The requirement for regulatory factors from both the perichondrium and periosteum suggests a novel mechanism of regulation. Positive regulation was observed with conditioned media from several cell types, with the most potent activity being from articular perichondrial cells and hypertrophic chondrocytes. PMID- 11784075 TI - Inhibition of polarizing activity in the anterior limb bud is regulated by extracellular factors. AB - Anterior-posterior patterning of the developing limb is largely viewed as a function of polarizing activity. Recent evidence in polydactylous mutants, however, indicates that development of proper pattern also requires the involvement of inhibitory pathways in the anterior limb that prevent secondary polarizing zone formation, thus limiting the number of digits produced. We report the novel finding that grafts of extracellular matrix from the Mouse Posterior Limb Bud-4 cell line can induce supernumerary digits, including digits with posterior phenotype, from anterior chick limb mesenchyme. Unlike previously described mechanisms of pattern specification during limb development, it is shown that the extracellular matrix effect is not associated with release of an active signal. Rather, evidence is presented suggesting that heparan sulfate moieties in extracellular matrix grafts bind an endogenous, extracellular factor involved in inhibition of anterior polarizing activity, leading to derepression of the anterior limb and induction of polarizing zone marker genes including Sonic hedgehog and Bone morphogenetic protein-2. PMID- 11784076 TI - The BMP antagonists Chordin and Noggin have essential but redundant roles in mouse mandibular outgrowth. AB - Here we investigate the roles of the Bone Morphogenetic Protein (BMP) antagonists Chordin and Noggin in development of the mandible, which is derived from the first branchial arch (BA1). Both genes are expressed in the pharynx during early mandibular outgrowth and later in the mandibular process. Mice mutant for either Nog or Chd have only mild mandibular defects; however, pups of the genotype Chd( /-);Nog(+/-) exhibit a range of mandibular truncation phenotypes, from normal to agnathia. A few embryos homozygous null for both genes survive to late gestation; many are agnathic, though a few have significant mandibular outgrowth. In mandibular explants, ectopic BMP4 rapidly induces expression of both Chd and Nog, consistent with results obtained in vivo with mutant embryos. Previous work has shown that FGF8 is a survival factor for cells populating the mandibular bud. We find that excess BMP4 represses Fgf8 transcription in mandibular explants. Embryos lacking these BMP antagonists often show a strong reduction in Fgf8 expression in the pharyngeal ectoderm, and increased cell death in the mandibular bud. We suggest that the variable mandibular hypoplasia in double mutants involves increased BMP activity downregulating Fgf8 expression in the pharynx, decreasing cell survival during mandibular outgrowth. PMID- 11784077 TI - Roles for zebrafish focal adhesion kinase in notochord and somite morphogenesis. AB - We have cloned zebrafish focal adhesion kinase (Fak) and analyzed its subcellular localization. Fak protein is localized at the cortex of notochord cells and at the notochord-somite boundary. During somitogenesis, Fak protein becomes concentrated at the basal region of epithelial cells at intersomitic boundaries. Phosphorylated Fak protein is seen at both the notochord-somite boundary and intersomitic boundaries, consistent with a role for Fak in boundary formation and maintenance. The localization of Fak protein to the basal region of epithelial cells in knypek;trilobite double mutant embryos shows that polarization of Fak distribution in the somite border cells is independent of internal mesenchymal cells. In addition, we show that neither Notch signaling through Suppressor of Hairless (SuH) nor deltaD is necessary for the wild-type segmental pattern of fak mRNA expression in the anterior paraxial mesoderm. However, nonsegmental expression of fak mRNA occurs with ectopic activation of Notch signaling through SuH and also in fused somite and beamter mutant embryos, indicating that there are multiple regulators of fak mRNA expression. Our results suggest that Fak plays a central role in notochord and somite morphogenesis. PMID- 11784078 TI - Time-lapse analysis of living mouse germ cell migration. AB - In mouse embryos, the primordial germ cells arise during gastrulation prior to, and distant from, the prospective gonads. Observations of PGCs in culture, and in fixed sections, have suggested, but not proved, that they migrate to the gonad by a process of active migration. The opaque nature of the early mouse embryo has precluded direct observation. Using confocal microscopy, we have filmed living PGCs expressing eGFP in tissue slices from mouse embryos at different stages of development. We find four clearly distinct phases of PGC migration. First, until E9.0-E9.5, PGCs are already highly motile, but do not leave the gut. Second, in the E9.0-E9.5 period, before the mesentery forms, PGCs very rapidly exit the gut, but do not migrate towards the genital ridges. Third, during the E10.0-E10.5 period, PGCs migrate directionally from the dorsal body wall into the genital ridges. In contrast to the prevailing model of germ cell migration, very few, if any, PGCs found in the gut mesentery at E10.5 migrate into the genital ridges. Finally, at E11.5, PGCs are slowing and the direction of movement is dependent on the sex of the embryo. This allows, for the first time, a formal description of the events of PGC migration in the mouse. PMID- 11784079 TI - Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function. AB - Numerous in vitro and in vivo studies implicate transforming growth factor-beta (TGFbeta) superfamily signaling in vascular development and maintenance. Mice and humans with mutations in TGFbeta superfamily signaling pathway genes exhibit a range of vascular defects that include dilated, fragile and hemorrhagic vessels, defective angiogenic remodeling, severe vascular malformations including arterio venous malformations, and disrupted vascular smooth muscle cell recruitment and maintenance. Despite a wealth of data, the functions of TGFbeta superfamily signals during angiogenesis are poorly defined, since early embryonic lethality and difficulty distinguishing between primary and secondary defects frequently confound phenotypic interpretation. To perturb TGFbeta superfamily signaling during angiogenesis, we have misexpressed Smad7, an intracellular antagonist of TGFbeta superfamily signaling, in the developing chick limb and head. We find that the great vessels are strikingly dilated and frequently develop intra and intervascular shunts. Neither noggin nor dominant negative BMP receptor misexpression causes similar vascular phenotypes. However, simultaneous misexpression of constitutively active BMP receptors with Smad7 suppresses the Smad7-induced phenotype, suggesting that a BMP-like intracellular pathway is the target of Smad7 action. Despite the gross morphological defects, further analyses find no evidence of hemorrhage and vessel structure is normal. Furthermore, enlarged vessels and vascular malformations form in either the presence or absence of vascular smooth muscle, and vascular smooth muscle cell recruitment is unperturbed. Our data define the TGFbeta superfamily pathway as an integral regulator of vessel caliber that is also essential for appropriate vessel connectivity. They demonstrate that dilation need not result in vessel rupture or hemorrhage, and dissociate vessel maintenance from the presence of a vascular smooth muscle cell coat. Furthermore they uncouple vascular smooth muscle cell recruitment and differentiation from TGFbeta superfamily signaling. PMID- 11784080 TI - Sgn1, a basic helix-loop-helix transcription factor delineates the salivary gland duct cell lineage in mice. AB - The salivary system in mammals is comprised of three independently developed pairs of organs, the parotid, submaxillar, and sublingual glands. Each gland is composed of various ductal and acinar cell types that fulfill multiple roles. However, the molecular mechanisms regulating their biogenesis and functions are still largely unknown. In this paper, we report that two class B basic helix-loop helix (bHLH) transcriptional regulators delineate the ductal and the acinar cells in salivary glands. Sgn1, a novel class B bHLH factor, is specifically expressed in the salivary duct cells, while the acinar cells are characterized by the expression of another class B bHLH factor, Mist1. The molecular nature of Sgn1 was also investigated: it binds to specific sequences of DNA as a dimer with a class A bHLH factor and acts as a negative transcriptional regulator against other bHLH factors. This study provides an important cue towards better understanding of the generation and function of multiple cell types in salivary glands. In addition, Sgn1 expression exhibits a reverse relationship with the development of male phenotypes, suggesting its role in gender dimorphism in the salivary glands. PMID- 11784081 TI - Identification of a CArG box-dependent enhancer within the cysteine-rich protein 1 gene that directs expression in arterial but not venous or visceral smooth muscle cells. AB - Smooth muscle cells (SMCs) are heterogeneous with respect to their contractile, synthetic, and proliferative properties, though the regulatory factors responsible for their phenotypic diversity remain largely unknown. To further our understanding of smooth muscle gene regulation, we characterized the cis regulatory elements of the murine cysteine-rich protein 1 gene (CRP1/Csrp1). CRP1 is expressed in all muscle cell types during embryogenesis and predominates in vascular and visceral SMCs in the adult. We identified a 5-kb enhancer within the CRP1 gene that is sufficient to drive expression in arterial but not venous or visceral SMCs in transgenic mice. This enhancer also exhibits region-specific activity in the outflow tract of the heart and the somites. Within the 5-kb CRP1 enhancer, we found a single CArG box that binds serum response factor (SRF), and by mutational analysis, demonstrate that the activity of the enhancer is dependent on this CArG element. Our findings provide further evidence for the existence of distinct regulatory programs within SMCs and suggest a role for SRF in the activation of the CRP1 gene. PMID- 11784082 TI - FGF signaling is necessary for the specification of the odontogenic mesenchyme. AB - Tooth development is initiated by signals from the oral ectoderm which induce gene expression required for tooth development in the underlying mesenchyme. In this study, we have used Su5402, an inhibitor of FGF receptor signaling, to analyze the requirement of FGF signaling during early tooth development. We show that FGF signaling is necessary for expression of Pax9, a transcription factor required for development of all teeth, in prospective incisor and molar mesenchyme until E11.0. Expression of the LIM homeobox gene Lhx7 also requires FGF signaling until E11.0 whereas expression of its homologue Lhx6 and the homeobox transcription factor Barx1 already becomes independent of FGF signaling at E10.75. In contrast, ectodermal expression of several genes thought to be important for tooth development was unaffected by the block of FGF signaling. Finally, we show that expression of the TGFbeta antagonist Dan in prospective tooth mesenchyme requires ectodermal signals and can be induced by FGF-soaked beads but is maintained in mandibular explants in the absence of FGF signaling. Together, these results demonstrate that FGF signaling is required for development of both molar and incisor teeth and suggest that specification of tooth mesenchyme involves at least two FGF-dependent steps. PMID- 11784083 TI - A dual role for the zebrafish unplugged gene in motor axon pathfinding and pharyngeal development. AB - On their way toward their synaptic targets, motor growth cones encounter multiple choice points, where they are confronted with trajectory choices. We have previously shown that the zebrafish unplugged gene acts as a somite-derived cue controlling pathway choice of primary motor axons. Here, we demonstrate that this trajectory choice is not exclusively controlled by a single unplugged-dependent process, but depends on the coordinated function of additional cues. We also show that secondary motor neurons, most similar to those in birds and mammals, depend on the unplugged gene to navigate a choice point, suggesting that primary and secondary motor neurons share common mechanisms controlling axonal path selection. Moreover, we show that the unplugged gene plays an additional role guiding secondary motor axons through a single segmental nerve. Finally, we report that unplugged larvae display a striking pharyngeal arch defect, consistent with a dual function of the unplugged gene in axonal guidance and cell motility. PMID- 11784084 TI - Cell density-dependent induction of endogenous myogenin (myf4) gene expression by Myf5. AB - Transcription factors Myf5 and MyoD are critical for myoblast determination. Myogenin is a direct transcriptional target of these factors and its expression is associated with commitment to terminal differentiation. Here, we have used myogenic derivatives of human U20S cells expressing Myf5 or MyoD under control of a tetracycline-sensitive promoter to study expression of endogenous myogenin (myf4). We find that Myf5-mediated induction of myogenin shows striking dependence on cell density. At high cell density, Myf5 is a potent inducer of myogenin expression. At low cell density, Myf5 (unlike MyoD) is a poor inducer of myogenin expression, whilst retaining the capacity to direct expression of other muscle-specific genes. The permissive influence of high cell density on myogenin induction by Myf5 is not a consequence of serum depletion or cell cycle arrest, but is mimicked by a disruption adjacent to the basic region of Myf5 (Myf5/mt) which reduces its DNA binding affinity for E-boxes without compromising its ability to transactivate a reporter gene driven by the myogenin promoter. Coculture of cells expressing wild-type Myf5 and Myf5/mt leads to reduced myogenin induction in Myf5/mt cells. We propose that at low cell density Myf5 inhibits induction of myogenin. PMID- 11784085 TI - Allele-specific non-CpG methylation of the Nf1 gene during early mouse development. AB - Recent reports of cytosine methylation occurring at CpA and CpT dinucleotides in murine ES cells as well as in Drosophila have renewed interest in methylation at sites other than CpGs. Our examination of the murine neurofibromatosis type 1 gene by sodium bisulfite genomic sequencing has revealed non-CpG methylation primarily in the oocyte and the maternally derived allele of the 2-cell embryo, with markedly lower levels found in sperm. Non-CpG methylation was not found in later stages of embryo development or in adult tissue. Our results suggest that maternal-specific de novo non-CpG methylation has occurred sometime between ovulation and formation of the 2-cell embryo, while during the same period the paternally derived allele has undergone site-specific active demethylation. Our data demonstrate both stage and parent-of-origin specific changes in methylation patterns within the neurofibromatosis type 1 coding region-involving cytosines located at both CpG and non-CpG dinucleotides. PMID- 11784086 TI - Expression and localization of caveolin-1, and the presence of membrane rafts, in mouse and Guinea pig spermatozoa. AB - In somatic cells, caveolin-1 plays several roles in membrane dynamics, including organization of detergent-insoluble lipid rafts, trafficking of cholesterol, and anchoring of signaling molecules. Events in sperm capacitation and fertilization require similar cellular functions, suggesting a possible role for caveolin-1 in spermatozoa. Immunoblot analysis demonstrated that caveolin-1 was indeed present in developing mouse male germ cells and both mouse and guinea pig spermatozoa. In mature spermatozoa, caveolin-1 was enriched in a Triton X-100-insoluble membrane fraction, as well as in membrane subdomains separable by means of their light buoyant densities through sucrose density gradient centrifugation. These data indicated the presence of membrane rafts enriched in caveolin-1 in spermatozoa. Indirect immunofluorescence analysis revealed caveolin-1 in the regions of the acrosome and flagellum in sperm of both species. Confocal immunofluorescence analysis of developing mouse male germ cells demonstrated partial co-localization with a marker for the acrosome. Furthermore, syntaxin-2, a protein involved in acrosomal exocytosis, was present in both raft and nonraft fractions in mature sperm. Together, these data indicated that sperm membranes possess distinct raft subdomains, and that caveolin-1 localized to regions appropriate for involvement with acrosomal biogenesis and exocytosis, as well as signaling pathways regulating such processes as capacitation and flagellar motility. PMID- 11784087 TI - drumstick, bowl, and lines are required for patterning and cell rearrangement in the Drosophila embryonic hindgut. AB - The Drosophila embryonic hindgut is a robust system for the study of patterning and morphogenesis of epithelial organs. We show that, in a period of about 10 h, and in the absence of significant cell division or apoptosis, the hindgut epithelium undergoes morphogenesis by changes in cell shape and size and by cell rearrangement. The epithelium concomitantly becomes surrounded by visceral mesoderm and is characterized by distinct gene expression patterns that forecast the development of three morphological subdomains: small intestine, large intestine, and rectum. At least three genes encoding putative transcriptional regulators, drumstick (drm), bowl, and lines (lin), are required to establish normal hindgut morphology. We show that the defect in hindgut elongation in drm, bowl, and lin mutants is due, in large part, to the requirement of these genes in the process of cell rearrangement. Further, we show that drm, bowl, and lin are required for patterning of the hindgut, i.e., for correct expression in the prospective small intestine, large intestine, and rectum of genes encoding cell signals (wingless, hedgehog, unpaired, Serrate, dpp) and transcription factors (engrailed, dead ringer). The close association of both cell rearrangement and patterning defects in all three mutants suggest that proper patterning of the hindgut into small intestine and large intestine is likely required for its correct morphogenesis. PMID- 11784088 TI - An analysis of hydrozoan gastrulation by unipolar ingression. AB - Unipolar ingression is a common form of gastrulation in the phylum Cnidaria. Here, this process is examined in the hydrozoan Phialidium. Ultrastructural investigation confirmed that, during this process, oral cells elongate, constricting at their apical ends and/or expanding at their basal ends as they ingress. Marking studies show that most entodermal cells originate from the oral area, but a few also come from lateral, aboral-lateral, and aboral areas. Based on orientation of mitotic spindles during gastrulation, a few cells may also enter the entodermal region by delamination. Cell sorting experiments showed that, by postgastrulation, cells from aboral areas of the preingression embryo developed lower adhesive capacities than those from oral regions. Differences in adhesive capacity may allow maintenance of distinct cell layers. Postgastrulae are shorter, thinner, and more streamlined than preingression embryos. Total embryo volume and cell volume decrease, the blastocoel disappears, and 34.4% of the cell mass becomes entoderm. Activities of the ectodermal layer play an important role in gastrulation: during gastrulation, aboral cells become more columnar and oral cells less columnar. Also, cells in oral and oral-lateral regions shift toward the midline, causing oral portions of the embryo to elongate. A model of unipolar ingression is proposed. PMID- 11784089 TI - Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b. AB - Inpp5b is an ubiquitously expressed type II inositol polyphosphate 5-phosphatase. We have disrupted the Inpp5b gene in mice and found that homozygous mutant males are infertile. Here we examine the causes for the infertility in detail. We demonstrate that sperm from Inpp5b(-/-) males have reduced motility and reduced ability to fertilize eggs, although capacitation and acrosome exocytosis appear to be normal. In addition, fertilin beta, a sperm surface protein involved in sperm-egg membrane interactions that is normally proteolytically processed during sperm transit through the epididymis, showed reduced levels of processing in the Inpp5b(-/-) animals. Inpp5b was expressed in the Sertoli cells and epididymis and at low levels in the developing germ cells; however, mice lacking Inpp5b in spermatids and not in other cell types generated by conditional gene targeting, were fully fertile. The abnormalities in mutant sperm function and maturation appear to arise from defects in the functioning of Sertoli and epididymal epithelial cells. Our results directly demonstrate a previously unknown role for phosphoinositides in normal sperm maturation beyond their previously characterized involvement in the acrosome reaction. Inpp5b(-/-) mice provide an excellent model to study the role of Sertoli and epididymal epithelial cells in the differentiation and maturation of sperm. PMID- 11784090 TI - APH-2/nicastrin functions in LIN-12/Notch signaling in the Caenorhabditis elegans somatic gonad. AB - Nicastrin is a recently identified member of high-molecular weight complexes containing presenilin. The Caenorhabditis elegans homolog of nicastrin, aph-2, was shown to be required for GLP-1/Notch signaling in the early embryo. In addition to the maternal-effect embryonic lethal phenotype, aph-2 mutant animals also display an egg-laying defect. We show that this latter defect is related to the SEL-12/presenilin egg-laying defect. We also show that aph-2 and sel-12 genetically interact and cooperate to regulate LIN-12/Notch signaling in the development of the somatic gonad. In addition, aph-2 and lin-12/Notch genetically interact. We illustrate a new role for aph-2 in facilitating lin-12 signaling in the somatic gonad, thus providing evidence that APH-2 is involved in both GLP 1/Notch- and LIN-12/Notch-mediated signaling events. Finally, we demonstrate that nicastrin can partially substitute for aph-2, suggesting a conservation of function between these proteins. PMID- 11784091 TI - Structure and function of the egg cortex from oogenesis through fertilization. PMID- 11784092 TI - Clonal analysis of stomatal development and patterning in Arabidopsis leaves. AB - Cell lineage has been used to explain the stomatal distribution in several plant species. We have used transgenic plants carrying a 35SGUS::Ac construct that produces clonal sectors to analyze the possible role of cell lineage during the establishment of stomatal patterning in Arabidopsis leaves. The analysis of sectors ranging from two to eighteen cells supports the conclusion that most stomatal complexes derive from a single and immediate precursor cell through a stereotyped pattern of three unequal cell divisions followed by a final equal one. In addition, it shows that the successive cell divisions take place at a constant angle (approximately 60 degrees ) with respect to the previous one. Interestingly, this angular dimension shifts from 60 degrees to 0 degrees in the last cell division that gives rise to the stoma. These sectors also reveal the development of both clockwise and counterclockwise patterns of cell divisions during stomatal development in approximately equal numbers. Our clonal analysis indicates that cell divisions involved in the development of stomatal complexes are probably the last ones contributing to epidermal growth and development. Finally, the stereotyped pattern of cell divisions that culminates in the formation of stomatal complexes indicates that cell lineage plays a very important role during stomatal pattern establishment. PMID- 11784094 TI - The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo. AB - The establishment of anterior-posterior polarity in the Caenorhabditis elegans embryo requires the activity of the maternally expressed par genes. We report the identification and analysis of a new par gene, par-5. We show that par-5 is required for asynchrony and asymmetry in the first embryonic cell divisions, normal pseudocleavage, normal cleavage spindle orientation at the two-cell stage, and localization of P granules and MEX-5 during the first and subsequent cell cycles. Furthermore, par-5 activity is required in the first cell cycle for the asymmetric cortical localization of PAR-1 and PAR-2 to the posterior, and PAR-3, PAR-6, and PKC-3 to the anterior. When PAR-5 is reduced by mutation or by RNA interference, these proteins spread around the cortex of the one-cell embryo and partially overlap. We have shown by sequence analysis of par-5 mutants and by RNA interference that the par-5 gene is the same as the ftt-1 gene, and encodes a 14 3-3 protein. The PAR-5 14-3-3 protein is present in gonads, oocytes, and early embryos, but is not asymmetrically distributed. Our analysis indicates that the par-5 14-3-3 gene plays a crucial role in the early events leading to polarization of the C. elegans zygote. PMID- 11784093 TI - Genetic mosaic analysis reveals that GATA-4 is required for proper differentiation of mouse gastric epithelium. AB - During mouse embryogenesis GATA-4 is expressed first in primitive endoderm and then in definitive endoderm derivatives, including glandular stomach and intestine. To explore the role of GATA-4 in specification of definitive gastric endoderm, we generated chimeric mice by introducing Gata4(-/-) ES cells into ROSA26 morulae or blastocysts. In E14.5 chimeras, Gata4(-/-) cells were represented in endoderm lining the proximal and distal stomach. These cells expressed early cytodifferentiation markers, including GATA-6 and ApoJ. However, by E18.5, only rare patches of Gata4(-/-) epithelium were evident in the distal stomach. This heterotypic epithelium had a squamous morphology and did not express markers associated with differentiation of gastric epithelial cell lineages. Sonic Hedgehog, an endoderm-derived signaling molecule normally down regulated in the distal stomach, was overexpressed in Gata4(-/-) cells. We conclude that GATA-4-deficient cells have an intrinsic defect in their ability to differentiate. Similarities in the phenotypes of Gata4(-/-) chimeras and mice with other genetically engineered mutations that affect gut development suggest that GATA-4 may be involved in the gastric epithelial response to members of the TGF-beta superfamily. PMID- 11784095 TI - Cooperative action of ADMP- and BMP-mediated pathways in regulating cell fates in the zebrafish gastrula. AB - It was shown in Xenopus and chick that Spemann's organizer activity is regulated through the negative action of Anti-Dorsalizing Morphogenetic Protein (ADMP). We report the characterization and functional properties of admp in zebrafish. admp expression profile is consistent with a role in the organizer, including the tail organizer. We studied admp function through overexpression experiments, with the use of a dominant-negative form (TR-ADMP) and of an antisense morpholino-modified oligonucleotide. Our results indicate that the ADMP pathway causes the restriction of anterior and axial fates and that ADMP, BMP2b, and BMP7 pathways have distinct actions but cooperate in establishing proper dorso-ventral regionalization. This is shown by partial rescue of the dorsalized mutant snailhouse and of the ventralized mutant chordino, upon admp and tr-admp RNA injection, respectively. Moreover, ADMP and BMP7 probably form heterodimers as shown by the ability of TR-ADMP and BMP7 to antagonize each other. We observed that a MYC-tagged ADMP was secreted and detected in the extracellular space, suggesting that admp could act at a distance. Simultaneous local inhibition of bmp function at the blastoderm margin and impairment of ADMP secretion led to the induction of secondary head structures, confirming that the two pathways cooperatively regulate organizer formation and activity. PMID- 11784096 TI - Three-dimensional ultrastructural analysis of RNA distribution within germinal granules of Xenopus. AB - The germ plasm is a specialized region of oocyte cytoplasm that contains determinants of germ cell fate. In Xenopus oocytes, the germ plasm is a part of the METRO region of mitochondrial cloud. It contains the germinal granules and a variety of coding and noncoding RNAs that include Xcat2, Xlsirts, Xdazl, DEADSouth, Xpat, Xwnt11, fatVg, B7/Fingers, C10/XFACS, and mitochondrial large and small rRNA. We analyzed the distribution of these 11 different RNAs within the various compartments of germ plasm during Xenopus oogenesis and development by using whole-mount electron microscopy in situ hybridization. Serial EM sections were used to reconstruct a three-dimensional image of germinal granule distribution within the METRO region of the cloud and the distribution of RNAs on the granules in oocytes and embryos. We found that, in the oocytes, the majority of RNAs were associated either with the precursor of germinal granules or with the germ plasm matrix. Only Xcat2, Xpat, and DEADSouth RNAs were associated with the mature germinal granules in oocytes, while only Xcat2 and Xpat were associated with germinal granules in embryos. However, Xcat2 was the only RNA that was consistently sequestered inside the germinal granules, while the others were located on the periphery. Xdazl, which functions in germ cell migration/formation, was detected on the matrix between granules. Later in development, Xcat2 mRNA was released from the germinal granules. This coincides with the timing of its translational derepression. These results demonstrate that there is a dynamic three-dimensional architecture to the germinal granules that changes during oogenesis and development. They also indicate that association of specific RNAs with the germinal granules is not a prerequisite for their serving a germ cell function; however, it may be related to their state of translational repression. PMID- 11784097 TI - Multiple nodal-related genes act coordinately in Xenopus embryogenesis. AB - Four nodal-related genes (Xnr1-4) have been isolated in Xenopus to date, and we recently further identified two more, Xnr5 and Xnr6. In the present functional study, we constructed cleavage mutants of Xnr5 (cmXnr5) and Xnr6 (cmXnr6) which were expected to act in a dominant-negative manner. Both cmXnr5 and cmXnr6 inhibited the activities of Xnr5 and Xnr6 in co-overexpression experiments. cmXnr5 also inhibited the activity of Xnr2, Xnr4, Xnr6, derriere, and BVg1, but did not inhibit the activity of Xnr1 or activin. Misexpression of cmXnr5 led to a severe delay in initiation of gastrulation and phenotypic changes, including defects in anterior structures, which were very similar to those seen in maternal VegT-depleted embryos. Further, although the expression of Xnr1, Xnr2, and Xnr4 was not delayed in these embryos, it was markedly reduced. Injection of cmXnr5 had no notable effect on expression of Xnr3, Xnr6, derriere, or siamois. Several mesodermal and endodermal markers also showed delayed and decreased expression during gastrulation in cmXnr5-injected embryos. These results suggest that, in early Xenopus embryogenesis, nodal-related genes may heterodimerize with other TGF-beta ligands, and further that one nodal-related gene alone is insufficient for mesendoderm formation, which may require the cooperative interaction of multiple nodal-related genes. PMID- 11784099 TI - Cellular dispersion patterns and phenotypes in the developing mouse superior colliculus. AB - The mammalian superior colliculus is structurally and functionally divided into two entities: superficial visual and deep multimodal motor. To discover the role, if any, of developmental processes in establishing separate tectal compartments, we have used highly unbalanced mouse chimaeras to mark cell dispersion pathways and trace cell lineages. Two forms of cell dispersion were detected: radial and tangential. Neither radial nor tangential forms of cell dispersion were found to exist on their own in any group of labeled cells. Radial cell dispersion was the predominant form of cell movement from the germinal zones and primarily associated with the differentiation of glutamatergic neurons. In contrast, tangential cell dispersion involved a minority of tectal cells, concentrated chiefly in the superficial layers and often associated with the upper aspects of radial columns. More scattered cells expressed gamma-aminobutyric acid (GABA) compared to columnar cells. Taken together, these results indicate separate developmental constraints for the development of glutamatergic and GABAergic neurons in the superior colliculus. PMID- 11784098 TI - Tissue origins and interactions in the mammalian skull vault. AB - During mammalian evolution, expansion of the cerebral hemispheres was accompanied by expansion of the frontal and parietal bones of the skull vault and deployment of the coronal (fronto-parietal) and sagittal (parietal-parietal) sutures as major growth centres. Using a transgenic mouse with a permanent neural crest cell lineage marker, Wnt1-Cre/R26R, we show that both sutures are formed at a neural crest-mesoderm interface: the frontal bones are neural crest-derived and the parietal bones mesodermal, with a tongue of neural crest between the two parietal bones. By detailed analysis of neural crest migration pathways using X-gal staining, and mesodermal tracing by DiI labelling, we show that the neural crest mesodermal tissue juxtaposition that later forms the coronal suture is established at E9.5 as the caudal boundary of the frontonasal mesenchyme. As the cerebral hemispheres expand, they extend caudally, passing beneath the neural crest-mesodermal interface within the dermis, carrying with them a layer of neural crest cells that forms their meningeal covering. Exposure of embryos to retinoic acid at E10.0 reduces this meningeal neural crest and inhibits parietal ossification, suggesting that intramembranous ossification of this mesodermal bone requires interaction with neural crest-derived meninges, whereas ossification of the neural crest-derived frontal bone is autonomous. These observations provide new perspectives on skull evolution and on human genetic abnormalities of skull growth and ossification. PMID- 11784100 TI - Cubitus interruptus acts to specify naked cuticle in the trunk of Drosophila embryos. AB - One function of the Wingless signaling pathway is to determine the naked, cuticle cell fate choice in the trunk epidermis of Drosophila larvae. The zinc finger protein Teashirt binds to the transactivator domain of Armadillo to modulate Wingless signaling output in the embryonic trunk and contributes to the naked cell fate choice. The Hedgehog pathway is also necessary for the correct specification of larval epidermal cell fate, which signals via the zinc finger protein, Cubitus interruptus. Here, we show that Cubitus interruptus also has a Wingless-independent function, which is required for the specification of the naked cell fate; previously, it had been assumed that Ci induces naked cuticle exclusively by regulation of wg. Wg and Hh signaling pathways may be acting combinatorially in the same, or individually in different, cells for this process, by regulating common sets of target genes. First, the loss of the naked cuticular phenotype in embryos lacking cubitus interruptus activity is very similar to that induced by a late loss of Wingless function. Second, overexpression of Cubitus interruptus causes the suppression of denticles (as Wingless does) in absence of Wingless activity in the anterior trunk. Using epistasis experiments, we conclude that different combinations of the three proteins Teashirt, Cubitus interruptus, and Armadillo are employed for the specification of naked cuticle at distinct positions both along the antero posterior axis and within individual trunk segments. Finally, biochemical approaches suggest the existence of protein complexes consisting of Teashirt, Cubitus interruptus, and Armadillo. PMID- 11784101 TI - JNK signaling pathway is required for efficient wound healing in Drosophila. AB - Efficient wound healing including clotting and subsequent reepithelization is essential for animals ranging from insects to mammals to recover from epithelial injury. It is likely that genes involved in wound healing are conserved through the phylogeny and therefore, Drosophila may be an useful in vivo model system to identify genes necessary during this process. Furthermore, epithelial movement during specific developmental processes, such as dorsal closure, ressembles of those seen in mammalian wound healing. As puckered (puc) gene is a target of the JUN N-terminal kinase signaling pathway during dorsal closure, we investigated puc gene expression during wound healing in Drosophila. We showed that puc gene expression is induced at the edge of the wound in epithelial cells and Jun kinase is phosphorylated in wounded epidermal tissues, suggesting that the JUN N terminal kinase signaling pathway is activated by a signal produced by an epidermal wound. In the absence of the Drosophila c-Fos homologue, puc gene expression is no longer induced. Finally, impaired epithelial repair in JUN N terminal kinase deficient flies demonstrates that the JUN N-terminal kinase signaling is required to initiate the cell shape change at the onset of the epithelial wound healing. We conclude that the embryonic JUN N-terminal kinase gene cassette is induced at the edge of the wound. In addition, Drosophila appears as a good in vivo model to study morphogenetic processes requiring epithelial regeneration such as wound healing in vertebrates. PMID- 11784102 TI - Analysis of Drosophila cyclin EI and II function during development: identification of an inhibitory zone within the morphogenetic furrow of the eye imaginal disc that blocks the function of cyclin EI but not cyclin EII. AB - The Drosophila cyclin E (DmcycE) gene gives rise to two transcripts encoding proteins that differ at their N termini, DmcycEII and DmcycEI. This study presents the first in vivo dissection of Cyclin E function. Ectopic expression studies using N- and C-terminal deletions of DmcycEI revealed that a region of 322 residues surrounding the cyclin box is sufficient to induce entry of G1 arrested larval eye imaginal disc cells into S phase. Ectopic expression of DmcycEI in the eye disc has been previously shown to drive anterior, but not posterior, G1-phase cells within the morphogenetic furrow (MF) into S phase. Significantly, ectopic expression of DmcycEII and N-terminal deletions of DmcycEI were able to drive all G1 cells within the morphogenetic furrow into S phase, while a C-terminal deletion of DmcycEI could not. The p21 homolog Dacapo was shown by yeast two-hybrid, coimmunolocalization, and in vivo functional studies not to be the mediator of the DmcycEI inhibition in posterior part of the MF. Taken together, these results reveal a novel zone within the posterior region of the MF where DmcycEI but not DmcycEII function is inhibited, and suggest that DmcycEII is a more potent inducer of S phase. PMID- 11784103 TI - Dynamic reprogramming of DNA methylation in the early mouse embryo. AB - Dynamic epigenetic modification of the genome occurs during early development of the mouse. Active demethylation of the paternal genome occurs in the zygote, followed by passive demethylation during cleavage stages, and de novo methylation, which is thought to happen after implantation. We have investigated these processes by using indirect immunofluorescence with an antibody to 5-methyl cytosine. In contrast to previous work, we show that demethylation of the male pronucleus is completed within 4 h of fertilisation. This activity is intricately linked with and not separable from pronucleus formation. In conditions permissive for polyspermy, up to five male pronuclei underwent demethylation in the same oocyte. Paternal demethylation in fertilised oocytes deficient for MBD2, the only candidate demethylase, occurred normally. Passive loss of methylation occurred in a stepwise fashion up to the morulae stage without any evidence of spatial compartmentalisation. De novo methylation was observed specifically in the inner cell mass (ICM) but not in the trophectoderm of the blastocyst and hence may have an important role in early lineage specification. This is the first complete and detailed analysis of the epigenetic reprogramming cycle during preimplantation development. The three phases of methylation reprogramming may have roles in imprinting, the control of gene expression, and the establishment of nuclear totipotency. PMID- 11784104 TI - Altered cell-type proportioning in Dictyostelium lacking adenosine monophosphate deaminase. AB - The proportions of prespore and prestalk cells in Dictyostelium discoideum are regulated so that they are size invariant and can adjust when the ratio is perturbed. We have found that disruption of the gene amdA that encodes AMP deaminase results in a significantly increased proportion of prestalk cells. Strains lacking AMP deaminase form short, thick stalks and glassy sori with less than 5% the normal number of spores. The levels of prestalk-specific mRNAs in amdA(-) cells are more than twice as high as those in wild-type strains and prespore-specific mRNAs are reduced. Using an ecmA::lacZ construct to mark prestalk cells, we found that amdA(-) null slugs have twice the normal number of prestalk cells. The number of cells expressing an ecmO::lacZ construct was not affected by loss of AmdA, indicating that the mutation results in an increase in PST-A prestalk cells rather than PST-O cells. This alteration in cell-type proportioning is a cell-autonomous consequence of the loss of AMP deaminase since mutant cells developed together with wild-type cells still produced excess prestalk cells and wild-type cells carrying the ecmA::lacZ construct formed normal numbers of prestalk cells when developed together with an equal number of amdA(-) mutant cells. PMID- 11784105 TI - The ability to develop an activity that transfers histones onto sperm chromatin is acquired with meiotic competence during oocyte growth. AB - Following fertilization, the oocyte remodels the sperm chromatin into the male pronucleus. As a component of this process, during meiotic maturation, oocytes develop an activity that transfers histones onto sperm DNA. To further characterize this activity, we tested whether oocytes at different stages of growth could, upon entry into metaphase of maturation, transfer histones onto sperm DNA, as judged by chromatin morphology and immunocytochemistry. Meiotically competent growing oocytes, which spontaneously enter metaphase upon culture, transferred histones onto sperm chromatin, whereas incompetent oocytes did not, even when treated with okadaic acid to induce germinal vesicle breakdown (GVBD) and chromosome condensation. When incompetent oocytes were cultured until they acquired the ability to undergo GVBD, only a small proportion also developed histone-transfer activity during maturation. However, this proportion significantly increased when the oocytes were cultured as granulosa-oocyte complexes. The failure of histone-transfer activity to develop in incompetent oocytes treated with okadaic acid was not linked to low H1 kinase activity nor rescued by injected histones. Because competent, but not incompetent, oocytes produce natural calcium oscillations, incompetent oocytes were exposed to SrCl2. One-third of treated oocytes produced at least one Ca2+ oscillation and, following insemination, the same proportion transferred histones onto sperm DNA. Histone transfer did not occur in oocytes pretreated with the Ca2+ chelator, BAPTA-AM. These results indicate that the ability to develop histone-transfer activity is acquired by growing oocytes near the time of meiotic competence, that it is separable from this event, and that it may be regulated through a Ca2+ dependent process. PMID- 11784106 TI - Heads or tails? Amphioxus and the evolution of anterior-posterior patterning in deuterostomes. AB - In Xenopus, the canonical Wnt-signaling pathway acting through beta-catenin functions both in establishing the dorso-ventral axis and in patterning the anterior-posterior axis. This pathway also acts in patterning the animal-vegetal axis in sea urchins. However, because sea urchin development is typically indirect, and adult sea urchins have pentamerous symmetry and lack a longitudinal nerve cord, it has not been clear how the roles of the canonical Wnt-signaling pathway in axial patterning in sea urchins and vertebrates are evolutionarily related. The developmental expression patterns of Notch, brachyury, caudal, and eight Wnt genes have now been determined for the invertebrate chordate Amphioxus, which, like sea urchins, has an early embryo that gastrulates by invagination, but like vertebrates, has a later embryo with a dorsal hollow nerve cord that elongates posteriorly from a tail bud. Comparisons of Amphioxus with other deuterostomes suggest that patterning of the ancestral deuterostome embryo along its anterior-posterior axis during the late blastula and subsequent stages involved a posterior signaling center including Wnts, Notch, and transcription factors such as brachyury and caudal. In tunicate embryos, in which cell numbers are reduced and cell fates largely determined during cleavage stages, only vestiges of this signaling center are still apparent; these include localization of Wnt-5 mRNA to the posterior cytoplasm shortly after fertilization and localization of beta-catenin to vegetal nuclei during cleavage stages. Neither in tunicates nor in Amphioxus is there any evidence that the canonical Wnt-signaling pathway functions in establishment of the dorso-ventral axis. Thus, roles for Wnt signaling in dorso-ventral patterning of embryos may be a vertebrate innovation that arose in connection with the evolution of yolky eggs and gastrulation by extensive involution. PMID- 11784107 TI - A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development. AB - The Wnt/beta-catenin signaling pathway plays multiple roles during embryonic development, only a few of which have been extensively characterized. Although domains of Wnt expression have been identified throughout embryogenesis, anatomical and molecular characterization of responding cells has been mostly unexplored. We have generated a transgenic zebrafish line that expresses a destabilized green fluorescent protein (GFP) variant under the control of a beta catenin responsive promoter. Early zygotic expression of this transgene (TOPdGFP) mirrors known domains of Wnt signaling in the embryo. Loss of Lef1 activity results in decreased reporter expression and posterior defects, while loss of Tcf3 (Headless, Hdl) activity does not alter reporter expression, even though it results in loss of forebrain structures. In addition, ectopic Wnt1 expression can activate the reporter. In older embryos, we identify a number of transgene expressing cell populations as novel sites of beta-catenin signaling. We conclude that our TOP-dGFP reporter line faithfully illustrates domains of beta-catenin activity and enables the identification of responsive cell populations. PMID- 11784108 TI - Muscle development and lineage-specific expression of CiMDF, the MyoD-family gene of Ciona intestinalis. AB - The expression pattern of CiMDF, the MyoD-family gene of Ciona intestinalis, was analyzed in unmanipulated and microsurgically derived partial embryos. CiMDF encodes two transcripts during development (coding for distinct proteins), the smaller of which, CiMDFa, was detected in maternal RNA. Zygotic activity of CiMDF initiated in cleaving embryos of 32-64 cells. Both CiMDFa and CiMDFb transcripts were detected at this time; however, CiMDFa accumulated more rapidly before declining in abundance such that, by the early tail-formation stage, CiMDFb was more prevalent. Microsurgical isolations of various lineage blastomeres from the eight-cell stage were used to analyze CiMDF expression in the two embryonic lineages that give rise to larval tail muscle-autonomously specified primary cells and conditionally specified secondary cells. CiMDFa and CiMDFb transcripts were detected in both lineages, suggesting that neither functioned in a lineage specific manner. The data also demonstrated that CiMDF expression was autonomous in the primary lineage (i.e., cells derived from the B4.1 blastomeres) and correlated with histospecific differentiation of muscle. In the secondary lineage (i.e., cells derived from the A4.1 and b4.2 blastomeres), CiMDF expression was conditional and, as in the primary lineage, correlated with muscle differentiation. These experiments reveal similar patterns of CiMDF activity in the primary and secondary muscle lineages and imply a requirement for the expression of this gene in both lineages during larval tail muscle development. PMID- 11784109 TI - The Caenorhabditis elegans EGL-26 protein mediates vulval cell morphogenesis. AB - In screens for Caenorhabditis elegans mutants defective in vulval morphogenesis, we isolated multiple mutants in which the uterus and the vulva fail to make a functional connection, resulting in an egg-laying defective phenotype. Two of these connection of gonad defective (Cog) mutants carry alleles of the egl-26 gene. We demonstrate that vulval lineages in egl-26 mutant animals are normal, but one vulval cell, vulF, adopts an abnormal morphology. This results in formation of an abnormally thick layer of vulval tissue at the apex of the vulva and a physical blockage of the exit to the vulva from the uterus. egl-26 was cloned and is predicted to encode a novel protein. Mosaic analysis indicates that egl-26 activity is required in the primary vulval lineage for vulF morphogenesis. Expression of a functional translational fusion of EGL-26 to GFP was observed within the primary vulval lineage only in vulE, which neighbors vulF. EGL-26 is localized at the apical edge of the vulE cell. It is thus possible that vulE acts to instruct morphological changes in the neighboring cell, vulF, in an interaction mediated by EGL-26. PMID- 11784110 TI - Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene. AB - LIM-Kinase (LIMK), including LIMK1 and LIMK2, is the only known catalytic protein among LIM-family molecules. It is well known that LIMK phosphorylates and inactivates cofilin, an actin-depolymerizing factor regulating actin reorganization, while in vivo functions have remained to be elucidated. In the present study, we generated Limk2 gene-deficient mice in which three LIMK2 isoforms were disrupted in a Cre-mediated fashion. Impaired cofilin phosphorylation was clearly observed in Limk2-/- fibroblasts stimulated with bradykinin or lysophosphatidic acid, thereby suggesting that Cdc42 or Rho dependent LIMK activation did not occur. However, Limk2-/- mice did not exhibit embryonic lethality or any phenotypic abnormalities in postnatal growth and development, except for spermatogenesis in the testis. The testes of Limk2-/- mice were smaller in size and partial degeneration of spermatogenic cells in the seminiferous tubules was apparent in association with increased apoptosis. In addition, the viability of Limk2-/- spermatogenic cells, when cultured under stressed conditions, was diminished. Furthermore, the potential for germ cells to differentiate in a regenerative state was severely impaired in Limk2-/- testis. Experimental hyperthermia induced impairment of ADF/cofilin phosphorylation and the formation of intranuclear cofilin inclusions in mutant germ cells. Based on these findings, we propose that LIMK2, especially the testis-specific isoform tLIMK2, plays an important role in proper progression of spermatogenesis by regulation of cofilin activity and/or localization in germ cells. PMID- 11784111 TI - Regulation of nodal signalling and mesendoderm formation by TARAM-A, a TGFbeta related type I receptor. AB - Nodal signalling is essential for many developmental events during vertebrate development, including the establishment of left-right asymmetry, of dorsoventral axis of the central nervous system, and endoderm and mesoderm formation. The zebrafish TGFbeta-related type I receptor, TARAM-A (Tar), is expressed in the prospective mesendodermal territory and, when activated, can transfate early blastomeres into endoderm, suggesting that Nodal and Tar may represent similar signalling pathways. We have analysed the functional relationships between those two pathways in zebrafish. We first demonstrate that tar and the zebrafish nodal genes cyc and sqt functionally interact. We also show that a dominant-negative isoform of Tar, TarMR, interferes specifically with the function of Cyc and Sqt in vitro, but does not interfere with the function of BMP2, another TGFbeta related molecule. TarMR interferes also with Nodal signalling in vivo since it enhances the phenotype of embryos with weakened Nodal signalling. Overexpression of tarMR in wild-type embryos interfered with the formation of endoderm-derived structures. Conversely, overexpression of tar enlarged the presumptive mesendodermal region at the onset of gastrulation. Together, our results point to Tar as an essential factor for endoderm formation and an important modulator of Nodal signalling, potentially representing one of the Nodal receptors. (c)2001 Elsevier Science. PMID- 11784112 TI - Posteriorization by FGF, Wnt, and retinoic acid is required for neural crest induction. AB - The neural crest is a unique cell population induced at the lateral border of the neural plate. Neural crest is not produced at the anterior border of the neural plate, which is fated to become forebrain. Here, the roles of BMPs, FGFs, Wnts, and retinoic acid signaling in neural crest induction were analyzed by using an assay developed for investigating the posteriorization of the neural plate. Using specific markers for the anterior neural plate border and the neural crest, the posterior end of early neurula embryos was shown to be able to transform the anterior neural plate border into neural crest cells. In addition, tissue expressing anterior neural plate markers, induced by an intermediate level of BMP activity, was transformed into neural crest by posteriorizing signals. This transformation was mimicked by bFGF, Wnt-8, or retinoic acid treatment and was also inhibited by expression of the dominant negative forms of the FGF receptor, the retinoic acid receptor, and Wnt signaling molecules. The transformation of the anterior neural plate border into neural crest cells was also achieved in whole embryos, by retinoic acid treatment or by use of a constitutively active form of the retinoic acid receptor. By analyzing the expression of mesodermal markers and various graft experiments, the expression of the mutant retinoic acid receptor was shown to directly affect the ectoderm. We thereby propose a two-step model for neural crest induction. Initially, BMP levels intermediate to those required for neural plate and epidermal specification induce neural folds with an anterior character along the entire neural plate border. Subsequently, the most posterior region of this anterior neural plate border is transformed into the neural crest by the posteriorizing activity of FGFs, Wnts, and retinoic acid signals. We discuss a unifying model where lateralizing and posteriorizing signals are presented as two stages of the same inductive process required for neural crest induction. PMID- 11784113 TI - A complex role for distal-less in crustacean appendage development. AB - The developing leg of Drosophila is initially patterned by subdivision of the leg into proximal and distal domains by the activity of the homeodomain proteins Extradenticle (Exd) and Distal-less (Dll). These early domains of gene expression are postulated to reflect a scenario of limb evolution in which an undifferentiated appendage outgrowth was subdivided into two functional parts, the coxapodite and telopodite. The legs of most arthropods have a more complex morphology than the simple rod-shaped leg of Drosophila. We document the expression of Dll and Exd in two crustacean species with complex branched limbs. We show that in these highly modified limbs there is a Dll domain exclusive of Exd but there is also extensive overlap in Exd and Dll expression. While arthropod limbs all appear to have distinct proximal and distal domains, those domains do not define homologous structures throughout arthropods. In addition, we find a striking correlation throughout the proximal/distal extent of the leg between setal-forming cells and Dll expression. We postulate that this may reflect a pleisiomorphic function of Dll in development of the peripheral nervous system. In addition, our results confirm previous observations that branch formation in multiramous arthropod limbs is not regulated by a simple iteration of the proximal/distal patterning module employed in Drosophila limb development. PMID- 11784114 TI - Intracellular cell-autonomous association of Notch and its ligands: a novel mechanism of Notch signal modification. AB - Notch (N) and its ligands, Delta (Dl) and Serrate (Ser), are membrane-spanning proteins with EGF repeats. They play an essential role in mediating proliferation and segregated differentiation of stem cells. One of the prominent features of N signal system is that its ligands are anchored to the plasma membrane, which allows the ligand/receptor association only between the neighboring cells. Various lines of evidences have verified this intercellular signal transmission, but there also have been implications that expression of Dl or Ser interferes cell-autonomously with the ability of the cell to receive N signal, implying that N and its ligands may interact in the same cell. Here, we demonstrate that N, Dl, and Ser cell-autonomously form homomeric or heteromeric complexes. The cell autonomous heteromeric complexes are not present on the cell surface, implying that the association occurs in the endoreticulum or Golgi apparatus. Expression of Dl or Ser cell-autonomously reduces the N-mediated HES-5 promoter activity, indicating that the cell-autonomous association alters the N signal receptivity. Intracellular deletion of Dl shows elevated activity of this dominant-negative effect. In vivo overexpression study suggests that the cell-autonomous function of Dl and Ser is independent of the ligand specificity and may be modulated by Fringe (Fg), which inhibits the formation of the cell-autonomous Dl/N or Ser/N complex. PMID- 11784115 TI - Cell cycle regulation of pEg3, a new Xenopus protein kinase of the KIN1/PAR 1/MARK family. AB - We report the characterization of pEg3, a Xenopus protein kinase related to members of the KIN1/PAR-1/MARK family. The founding members of this newly emerging kinase family were shown to be involved in the establishment of cell polarity and both microtubule dynamic and cytoskeleton organization. Sequence analyses suggest that pEg3 and related protein kinases in human, mouse, and Caenorhabditis elegans might constitute a distinct group in this family. pEg3 is encoded by a maternal mRNA, polyadenylated in unfertilized eggs and specifically deadenylated in embryos. In addition to an increase in expression, we have shown that pEg3 is phosphorylated during oocyte maturation. Phosphorylation of pEg3 is cell cycle dependent during Xenopus early embryogenesis and in synchronized cultured XL2 cells. In embryos, the kinase activity of pEg3 is correlated to its phosphorylation state and is maximum during mitosis. Using Xenopus egg extracts we demonstrated that phosphorylation occurs at least in the noncatalytic domain of the kinase, suggesting that this domain might be important for pEg3 function. PMID- 11784116 TI - ced-10 Rac and mig-2 function redundantly and act with unc-73 trio to control the orientation of vulval cell divisions and migrations in Caenorhabditis elegans. AB - Vulval development in the nematode Caenorhabditis elegans can be divided into a fate specification phase controlled in part by let-60 Ras, and a fate execution phase involving stereotypical patterns of cell division and migration controlled in part by lin-17 Frizzled. Since the small GTPase Rac has been implicated as a downstream target of both Ras and Frizzled and influences cytoskeletal dynamics, we investigated the role of Rac signaling during each phase of vulval development. We show that the Rac gene ced-10 and the Rac-related gene mig-2 are redundantly required for the proper orientation of certain vulval cell divisions, suggesting a role in spindle positioning. ced-10 Rac and mig-2 are also redundantly required for vulval cell migrations and play a minor role in vulval fate specification. Constitutively active and dominant-negative mutant forms of mig-2 cause vulval defects that are very similar to those seen in ced-10;mig-2 double loss-of-function mutants, indicating that they interfere with the functions of both ced-10 Rac and mig-2. Mutations in unc-73 (a Trio-like guanine nucleotide exchange factor) cause similar vulval defects, suggesting that UNC-73 is an exchange factor for both CED-10 and MIG-2. We discuss the similarities and differences between the cellular defects seen in Rac mutants and let-60 Ras or lin-17 Frizzled mutants. PMID- 11784118 TI - Wound healing: the role of gap junctional communication in rat granulation tissue maturation. AB - Granulation tissue maturation is dependent upon the orientation of collagen fibers and cell differentiation. Gap junctions are intercellular membrane gated channels that facilitate direct communication between cells known as gap junctional intercellular communication (GJIC). The hypothesis is that GJIC modulates the maturation of granulation tissue during wound repair. In vitro, GJIC optimizes fibroblast-populated collagen lattice contraction and influences cell morphology. It is reported that LiCl increases GJIC in cultured cardiac myocytes. Polyvinyl alcohol (PVA) sponge implants with central reservoirs were placed within separate subcutaneous pockets on the backs of adult male Sprague Dawley rats. Each PVA implant received either 20 mM LiCl or saline injections on days 5, 7, and 10 after implantation. On day 11 implants were harvested and processed for light microscopy. By H&E staining LiCl-treated implants showed increased vascularization and decreased cell density compared to saline controls. Polarized light microscopy of Sirius red-stained specimens revealed more intense collagen fiber birefringence secondary to dense, parallel-organized collagen fiber bundles after LiCl treatment. This suggests that LiCl enhancement of GJIC between fibroblasts advances the maturation of granulation tissue. It is proposed that the degree of GJIC between granulation tissue fibroblasts influences both the quantity and the quality of granulation tissue deposited during the wound healing process. PMID- 11784117 TI - IL-12p40(-/-) mice treated with intratracheal bleomycin exhibit decreased pulmonary inflammation and increased fibrosis. AB - Pulmonary lymphohistiocytic inflammation and fibrosis characterize bleomycin (BLM) lung injury. IL-12, a p70 cytokine produced primarily by macrophages and dendritic cells, promotes T-helper-1-mediated inflammation. IL-12 production by blood monocytes and bronchoalveolar large mononuclear cells (BAMC) was investigated at Days 1-14 following intratracheal administration of BLM. In the lung, BAMC showed a large peak of IL-12 expression at Day 5 that returned rapidly toward baseline. IL-12p40(-/-) mice treated with BLM intratracheally showed less pulmonary mononuclear cell inflammation at Day 7 than wild-type controls, whereas pulmonary fibrosis and hydroxyproline content were increased in IL-12p40(-/-) mice at Day 14. The expression of IP-10, RANTES, and eotaxin were decreased in IL 12p40(-/-) mice and lung IL-6 expression was increased, all compared to controls. We conclude that IL-12 promotes the lymphohistiocytic response to BLM and may inhibit the late development of pulmonary fibrosis. PMID- 11784119 TI - The Mallory body as an aggresome: in vitro studies. AB - Prior in vivo studies supported the concept that Mallory bodies (MBs) are aggresomes of cytokeratins 8 and 18. However, to test this hypothesis an in vitro model is needed to study the dynamics of MB formation. Such a study is difficult because MBs have never been induced in tissue culture. Therefore, MBs were first induced in vivo in drug-primed mice and then primary cultures of hepatocytes from these mice were studied. Two approaches were utilized: 1. Primary cultures were transfected with plasmids containing the sequence for cytokeratin 18 (CK 18) tagged with green fluorescent protein (GFP). 2. Immunofluorescent staining was used to localize the ubiquitin-proteasome pathway components involved in MB aggresome complex formation in primary hepatocyte cultures. The cells were double stained with a ubiquitin antibody and one of the following antibodies: CK 8, CK 18, tubulin, mutant ubiquitin (UBB+1), transglutaminase, phosphothreonine, and the 20S and 26S proteasome subunits P25 and Tbp7, respectively. In the first approach, fluorescence was observed in keratin filaments and MBs 48 h after the cells were transfected with the CK 18 GFP plasmid. Nascent cytokeratin 18 was preferentially concentrated in MBs. Less fluorescence was observed in the normal keratin filaments. This indicated that MBs continued to form in vitro. The immunofluorescent staining of the hepatocytes showed that CK 8 and 18, ubiquitin, mutant ubiquitin (UBB+1), P25, Tbp7, phosphothreonine, tubulin, and transglutaminase were all located at the border or the interior of the MB. These results support the concept that MBs are aggresomes of CK 8 and CK18 and are a result of inhibition of the ubiquitin-proteasome pathway of protein degradation possibly caused by UBB+1. PMID- 11784121 TI - Viral papillomatosis in Florida manatees (Trichechus manatus latirostris). AB - The Florida manatee (Trichechus manatus latirostris) is one of the most endangered marine mammals in American coastal waters. Naturally resistant to infectious disease, the manatee immune system appears highly developed to protect it against the harsh marine environment and the effects of human-related injury. In 1997, seven captive Florida manatees developed multiple, cutaneous, pedunculated papillomas over a period of 6 months. Approximately 3 years later, four of the seven manatees developed multiple, cutaneous, sessile papillomas topically and clinically distinct from the initial lesions, some of which are still present. Histologic, ultrastructural, and immunohistochemical features indicated that the two distinct phenotypic lesions were caused by papillomaviruses (PVs). Preliminary immunologic data correlated with daily clinical observations suggested that the manatees were immunologically suppressed and that the papillomas were caused by activation of latent PV infections and reinoculation from active infections. The emergence of PV-induced papillomas in captive manatees, the possibility of activation of latent infection or transmission of active infection to free-ranging manatees, and the underlying cause of immune suppression predisposing manatees to develop viral papillomatosis are serious concerns for the future management of this highly endangered species. PMID- 11784120 TI - Respiratory reovirus 1/L induction of diffuse alveolar damage: a model of acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is a clinical syndrome that is characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. In this report we describe a unique animal model in which CBA/J mice infected with reovirus serotype 1, strain Lang develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consists of the overlapping phases of exudation including the formation of hyaline membranes, regeneration, and healing via resolution and/or repair with fibrosis. While the consequences of a number of infectious and noninfectious insults in various animal systems have been developed as models of human ARDS, they are models of acute lung injury and are of short-term duration. Therefore, they do not recapitulate all of the clinical and pathological phases observed in human ARDS. Thus, study of the cellular and molecular factors involved in these distinct phases of the disease have been limited. Reovirus 1/L infection of CBA/J mice will allow investigations of the pathophysiology of ARDS as it progresses from the initial stages of edema and neutrophilia to fibrotic lesion development in late stages. PMID- 11784122 TI - Generation of genetically altered mouse models for aging studies. AB - A number of mouse models have been identified and are being used for aging and age-associated disease research. However, the use of the genetically manipulated mouse model is still a relatively untapped resource for the study of the biology of aging. Genetically altered mice can be powerful tools for biology of aging research because gene expression can be controlled and correlated with established biomarkers. Standard transgene overexpression and gene targeting techniques were modified and used to generate 30 mouse lines during a 4-year period. These lines include models of Werner's syndrome (premature aging or progeria), Alzheimer's disease, other neurodegenerative condition, atherosclerosis, diabetes, immune dysfunction, musculoskeletal disorders, and oxidative stress. These new mouse models are providing additional insights into aging processes and will be useful for developing intervention strategies and collaborative interactions. PMID- 11784123 TI - Clonotypic analysis of T cells accumulating at arthritic lesions in HTLV-I env-pX transgenic rats. AB - Human T cell leukemia virus type I (HTLV-I) env-pX transgenic rats (env-pX rats) develop chronic destructive arthritis resembling rheumatoid arthritis in humans. Immunological characteristics were compared with those of collagen-induced arthritis (CIA). Rheumatoid factor was present in some env-pX rats regardless of the development of arthritis, but not in nontransgenic rats with CIA. All rats with CIA produced anti-type II collagen (IIC) antibody, but never so in env-pX rats with naturally occurring arthritis. Although expansions of oligoclonal T cells were evident in the affected joints, no particular clone was shown to infiltrate into the arthritic lesions in env-pX rats. In contrast to CIA, in which clonal expansions of IIC-specific T cells are implicated, locally expanded T cell clones against various antigens of the joints may play pathogenetic roles in the arthritis seen in env-pX rats. However, complementarity-determining region 3 of the TCR Vbeta gene of T cells accumulating at the affected joints in env-pX rats contained the GGA amino acid sequence, which was reported to be a conserved motif in HTLV-I env-pX transgenic mice with arthritis. These findings suggest that common antigen(s) might be recognized by T cells accumulating at sites of arthritis in both transgenic rats and mice. PMID- 11784124 TI - Differential effects of TPA and retinoic acid on cell-cell communication in human bronchial epithelial cells. AB - Understanding how normal and immortalized bronchial epithelial cells respond to modulators of gap junctional communication will increase our understanding of the process of tumor promotion. In the present study we compared to effects of retinoic acid (RA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the rate of fluorescent dye transfer via gap junctions in primary human tracheo-bronchial epithelial cells (TBE) and SV40 large T-antigen immortalized, non-tumorigenic bronchial epithelial cells (BEAS-2B). RA in the physiological range (0.001-1 microM) inhibited cell proliferation (DNA synthesis, mitotic index) more in primary TBE cells than BEAS-2B cells. Also in RA-treated cells, decreased cell proliferation was coupled to decreased gap junctional communication (GJC) in TBE but not in BEAS-2B cells. TPA strongly suppressed GJC and proliferation in primary TBE cells, whereas BEAS-2B exhibited increased GJC and retained a significant fraction of cells undergoing DNA synthesis. Our studies show that an uncoupling of GJC and cell proliferation is associated with a differential response to the growth inhibitory effects of RA and phorbol esters in immortalized compared to primary human bronchial epithelial cells. PMID- 11784125 TI - Mice genetically lacking endothelial selectins are resistant to the lethality in septic peritonitis. AB - Leukocyte interactions with vascular endothelium are an initial step for leukocyte entry into infectious foci where endothelial selectins may play a key role. Infiltrating leukocyte is essential for bacterial clearance, suggesting that endothelial selectins would be important in host defense against microorganisms. To address this, E-, P-, and E/P-selectin-deficient mice (E(-/-), P(-/-), E/P(-/-)) and wild-type (WT) mice underwent cecal ligation and puncture (CLP). Neither leukocyte infiltration nor bacterial load in the peritoneum was altered in E(-/-), P(-/-), and E/P(-/-) mice compared to WT mice. However, E(-/ ), P(-/-), and E/P(-/-) mice were resistant to the lethality induced by CLP. At the mechanistic level, E(-/-), P(-/-), and E/P(-/-) mice did not develop renal dysfunction, a possible cause of death during sepsis. The serum level of interleukin-13 in E(-/-), P(-/-), and E/P(-/-) mice that had undergone CLP was higher than that in WT mice, whereas levels of macrophage inflammatory protein-2, KC in serum, and KC in kidney were lower than those in WT mice. These experiments demonstrate that endothelial selectin-mediated leukocyte rolling is not required for leukocyte entry in septic peritonitis and that endothelial selectins may affect mice survival during sepsis by influencing the cytokine profiles. PMID- 11784126 TI - Diagnostic value of detection of IgM antibodies to Helicobacter pylori. AB - This report describes the diagnostic value of anti-Helicobacter pylori IgM detection. Serum samples from 9043 symptomatic and asymptomatic individuals were evaluated with ELISA for the presence of anti-H. pylori IgG, IgM, and IgA. The specificity of detected IgM was confirmed by inhibition and cross-reactivity assays. Treatment of IgM-positive specimens with 1% 2-mercaptoethanol resulted in approximately 90% inhibition. Our data suggest a low level of cross-reactivity (5%) between H. pylori and four different enteropathogenic bacteria tested. The specificity of anti-H. pylori IgM was also demonstrated by Western blot and linearity studies. Data show that the detected IgM is highly specific. Western blot analysis revealed a variable IgM response to H. pylori antigens among patients, with the most reactive antigenic fractions being in the range of 55- to 100-kDa. Overall, the data confirm the diagnostic value of anti-H. pylori IgM detection. The prevalence of IgM antibodies to H. pylori in tested sera was significantly higher in symptomatic patients (10.4%) than in asymptomatic individuals (1.1%). Likewise, the percentage of sera positive for IgM alone was higher in symptomatic than in asymptomatic groups (3.8 vs 0.22%). About 5% of sera were positive only for IgA. We concluded that ELISA can be used for the detection of specific IgM to H. pylori and that the presence or absence of IgM antibodies to H. pylori may reflect whether or not an acute infection exists. PMID- 11784127 TI - Role of placental alkaline phosphatase in the interaction between human placental trophoblast and Trypanosoma cruzi. AB - Congenital Chagas disease, due to the intracellular parasite Trypanosoma cruzi, is associated with premature labor, miscarriage, and placentitis. Human enzyme placental alkaline phosphatase (PLAP) (EC 3.1.3.1.) is membrane-anchored through glycosylphosphatidylinositol (GPI). PLAP is present in plasma in late pregnancy, 36 to 40 weeks; there are lower levels in maternal Chagas disease. Infants born to such mothers may have congenital Chagas disease. Human placental villi (PV) were treated with phospholipase-C (PL-C) and then cultured with T. cruzi to determine the effect of the parasites on PLAP activity as an in vitro model. There is less PLAP activity after treatment by PL-C and during culture with T. cruzi. Pretreatment of PV with PL-C before culture with T. cruzi yielded essentially normal specific activity of PLAP and prevented or greatly reduced infective penetration of villi by parasites. The results are consistent with a pathogenetic role for placental alkaline phosphatase in congenital Chagas disease. Receptor activation of membrane attachment to PLAP may be a device used by T. cruzi to enable parasite invasion of human trophoblast. PMID- 11784128 TI - Looking for selectivity among cytochrome P450s inhibitors. AB - Cytochrome P450s 19 and 17 are very important pharmacological targets in two different fields of cancer chemotherapy. We present here a theoretical study aimed at explaining the molecular basis of inhibitor affinity and selectivity for either P450 19 or P450 17. Docking simulations of two compounds pointed out the major physicochemical features associated with inhibitory activity. Our results, in agreement with site-directed mutagenesis experiments, could be of relevant utility when designing new P450 19 and P450 17 inhibitors. PMID- 11784129 TI - Bacteriopurpurinimides: highly stable and potent photosensitizers for photodynamic therapy. AB - The in situ conversion of the unstable bacteriochlorophyll a present in Rhodobacter sphaeroides produced highly stable bacteriopurpurin-18 which in a sequence of reactions was converted into a series of alkyl ether analogues of bacteriopurpurin-18-N-alkylimides with long wavelength absorption near 800 nm. The effective photosensitizers were found to localize in mitochondria but did not show any specific displacement of (3)H-PK11195, suggesting that the mitochondrial peripheral benzodiazepine receptor is not the cellular binding site for this class of compounds. PMID- 11784130 TI - Design of substrate-based inhibitors of human beta-secretase. AB - By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor 22 resulted in no loss of potency (23). C-terminal truncations of inhibitor 22 generally led to significant loss of potency. PMID- 11784131 TI - Inhibition of nNOS activity in rat brain by synthetic kynurenines: structure activity dependence. AB - The overstimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is involved in excitotoxicity, a process participating in neurodegeneration that characterizes some neurological disorders and acute cerebral insults. In looking for compounds with neuroprotective properties, a series of kynurenine derivatives were synthesized, and their effects on both the NMDA and nNOS activity in rat striatum were evaluated. Two compounds, 15a (2 acetamido-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acid) and 15c (2-butyramido-4 (2-amino-5-methoxyphenyl)-4-oxobutyric acid), displayed more potent activities than the other synthetic compounds tested for the inhibition of NMDA excitability and nNOS activity. Two other compounds, 18a (2-acetamido-4-(3-methoxyphenyl)-4 oxobutyric acid) and 18c (2-butyramido-4-(3-methoxyphenyl)-4-oxobutyric acid), that have the same structure as 15a and 15c, except the amino group in R(1), showed different effects. Whereas compound 18a showed lower electrophysiological potency than compounds 15a and 15c in the inhibition of the NMDA-dependent excitability, compound 18c showed the opposite effect. Moreover, compounds 18a and 18c were unable to modify nNOS activity. The remaining kynurenines tested behave like compound 18a. These results suggest that a structure-related activity of these synthetic kynurenines and a N-H bond in a specific direction is necessary for some kynurenine analogues to inhibit nNOS activity. PMID- 11784132 TI - Antagonistic effects of human cyclic MBP(87-99) altered peptide ligands in experimental allergic encephalomyelitis and human T-cell proliferation. AB - The immunodominant myelin basic protein (MBP) peptide comprising residues 87-99 is a self-antigen in multiple sclerosis (MS). In Lewis rats this epitope induces experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, and is a model of MS. Structure-activity studies have shown that Lys(91) and Pro(96) residues are important for encephalitogenicity. Replacement of Lys and/or Pro residues with Arg and/or Ala, respectively, results in suppression of EAE. A potent linear altered peptide ligand of the immunodominant sequence MBP(83-99) has been selected for clinical trial (Nat. Med. 2000, 6, 1167, 1176). In the present report, two cyclic analogues, cyclo(91 99)[Ala(96)]MBP(87-99) and cyclo(87-99)[Arg(91), Ala(96)]MBP(87-99) were designed by NMR and molecular modeling data on human MBP(87-99) epitope (Val(87)-His-Phe Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro(99)) and its linear antagonist peptide analogue [Arg(91), Ala(96)]MBP(87-99). These analogues (altered peptide ligands) inhibited EAE in Lewis rats and decreased inflammation in the spinal cord. In addition, the analogue cyclo(87-99)[Arg(91), Ala(96)]MBP(87-99) induced proliferation of human peripheral blood T-cells. These cyclic MBP(87-99) peptide analogues may lead to the design of potent antagonist mimetics for treating MS. PMID- 11784133 TI - Carbonic anhydrase activators: high affinity isozymes I, II, and IV activators, incorporating a beta-alanyl-histidine scaffold. AB - A novel class of tight binding carbonic anhydrase (CA) activators was designed by using histamine and histidine as lead molecules. Carnosine (beta-Ala-His) derivatives were synthesized by reaction of appropriately derivatized beta alanines with imidazole/carboxy-protected histidine in the presence of carbodiimides, followed by removal of the various protecting groups. The derivatized beta-alanines mentioned above were in turn obtained by coupling of 4 fluorophenylsulfonylureido amino acids (fpu-AA) or 2-toluenesulfonylureido amino acids (ots-AA) with beta-Ala. Some structurally related dipeptides with the general formula fpu/ots-AA1-AA2 (AA, AA1, and AA2 represent amino acyl moieties) were also prepared by a similar strategy and used thereafter for obtaining CA activators incorporating a modified tetrapeptide scaffold. Many of the new tri /tetrapeptide derivatives reported here proved to be efficient in vitro activators of three CA isozymes. Very good activity was detected against hCA I and bCA IV, for which some of the new compounds showed affinities in the 1-20 nM range (h = human; b = bovine isozymes), whereas against hCA II, their affinities were in the range of 10-40 nM. Ex vivo experiments showed some of the new activators to strongly enhance cytosolic red cell CA activity after incubation with human erythrocytes. This new class of CA activators might lead to the development of drugs/diagnostic tools for the management of CA deficiency syndromes, as well as for the pharmacological enhancement of synaptic efficacy, spatial learning, and memory. This may constitute a new approach for the treatment of Alzheimer's disease and other conditions in need of achieving memory therapy. PMID- 11784134 TI - Structure-activity relationships of the antimalarial agent artemisinin. 6. The development of predictive in vitro potency models using CoMFA and HQSAR methodologies. AB - Artemisinin (1) is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua L. Because of the effectiveness of Artemisinin in the treatment of drug-resistant Plasmodium falciparum and its rapid clearance of cerebral malaria, development of clinically useful semisynthetic drugs for severe and complicated malaria (artemether, artesunate) was prompt. However, recent reports of fatal neurotoxicity in animals with dihydroartemisinin derivatives such as artemether have spawned a renewed effort to develop nontoxic analogues of artemisinin. In our effort to develop more potent, less neurotoxic agents for the oral treatment of drug-resistant malaria, we utilized comparative molecular field analysis (CoMFA) and hologram QSAR (HQSAR), beginning with a series of 211 artemisinin analogues with known in vitro antimalarial activity. CoMFA models were based on two conformational hypotheses: (a) that the X-ray structure of artemisinin represents the bioactive shape of the molecule or (b) that the hemin docked conformation is the bioactive form of the drug. In addition, we examined the effect of inclusion or exclusion of racemates in the partial least squares (pls) analysis. Databases derived from the original 211 were split into chiral (n = 157), achiral (n = 34), and mixed databases (n = 191) after leaving out a test set of 20 compounds. HQSAR and CoMFA models were compared in terms of their potential to generate robust QSAR models. The r(2) and q(2) (cross-validated r(2)) were used to assess the statistical quality of our models. Another statistical parameter, the ratio of the standard error to the activity range (s/AR), was also generated. CoMFA and HQSAR models were developed having statistically excellent properties, which also possessed good predictive ability for test set compounds. The best model was obtained when racemates were excluded from QSAR analysis. Thus, CoMFA of the n = 157 database gave excellent predictions with outstanding statistical properties. HQSAR did an outstanding job in statistical analysis and also handled predictions well. PMID- 11784135 TI - Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates. AB - This paper describes a graphical model for simplifying in vitro absorption, metabolism, distribution, and elimination (ADME) data analysis through the estimation of oral bioavailability (%F) of drugs in humans and other species. This model integrates existing in vitro ADME data, such as Caco-2 permeability (P(app)) and metabolic stability (percent remaining - %R) in liver S9 or microsomes, to estimate %F into groups of low, medium, or high regions. To test the predictive accuracy of our model, we examined 21 drugs and drug candidates with a wide range of oral bioavailability values, which represent approximately 10 different therapeutic areas in humans, rats, dogs, and guinea pigs. In vitro data from model compounds were used to define the boundaries of the low, medium, and high regions of the %F estimation plot. On the basis of the in vitro data, warfarin (93%), indomethacin (98%), timolol (50%), and carbamazepine (70%) were assigned to the high %F region; propranolol (26%) and metoprolol (38%) to medium %F region; and verapamil (22%) and mannitol (18%) to the low %F region. Similarly, the %F of 11 drug candidates from Elastase Inhibitor, NK1/NK2 antagonist, and anti-viral projects in rats, guinea pigs, and dogs were correctly estimated. This model estimates the oral bioavailability ranges of neutral, polar, esters, acidic, and basic drugs in all species. For a large number of drug candidates, this graphical model provides a tool to estimate human oral bioavailability from in vitro ADME data. When combined with the high throughput in vitro ADME screening process, it has the potential to significantly accelerate the processes of lead identification and optimization. PMID- 11784136 TI - Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. AB - A series of aromatic/heterocyclic sulfonamides incorporating valproyl moieties were prepared to design antiepileptic compounds possessing in their structure two moieties known to induce such a pharmacological activity: valproic acid, one of the most widely used antiepileptic drugs, and the sulfonamide residue included in acetazolamide and topiramate, two carbonic anhydrase inhibitors with antiepileptic properties. Some of these derivatives showed very high inhibitory potency against three carbonic anhydrase (CA) isozymes, such as CA I, CA II, and CA IV, involved in important physiological processes. Topiramate, a recently developed antiepileptic drug possessing a sulfamate moiety, also shares this property, although earlier literature data reported this compound to be a weak moderate CA I, II, and IV inhibitor. The valproyl derivative of acetazolamide (5 valproylamido-1,3,4-thiadiazole-2-sulfonamide, 6M) was one of the best hCA I and hCA II inhibitor in the series and exhibited very strong anticonvulsant properties in an MES test in mice. In consequence, other 1,3,4 thiadiazolesulfonamide derivatives possessing potent CA inhibitory properties and substituted with different alkyl/arylcarboxamido/sulfonamido/ureido moieties in the 5 position have been investigated for their anticonvulsant effects in the same animal model. It was observed that some lipophilic derivatives, such as 5 benzoylamido-, 5-toluenesulfonylamido-, 5-adamantylcarboxamido-, and 5 pivaloylamido-1,3,4-thiadiazole-2-sulfonamide, show promising in vivo anticonvulsant properties and that these compounds may be considered as interesting leads for developing anticonvulsant or selective cerebrovasodilator drugs. PMID- 11784137 TI - Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. AB - Twelve analogues of diclofenac (1), a nonsteroidal antiinflammatory drug and known inhibitor of transthyretin (TTR) amyloid formation, were prepared and evaluated as TTR amyloid formation inhibitors. High activity was exhibited by five of the compounds. Structure-activity relationships reveal that a carboxylic acid is required for activity, but changes in its position as well as the positions of other substituents are tolerated. High-resolution X-ray crystal structures of four of the active compounds bound to TTR were obtained. These demonstrate the significant flexibility with which TTR can accommodate ligands within its two binding sites. PMID- 11784138 TI - Elucidating the inhibiting mode of AHPBA derivatives against HIV-1 protease and building predictive 3D-QSAR models. AB - The Lamarckian genetic algorithm of AutoDock 3.0 has been used to dock 27 3(S) amino-2(S)-hydroxyl-4-phenylbutanoic acids (AHPBAs) into the active site of HIV-1 protease (HIVPR). The binding mode was demonstrated in the aspects of the inhibitor's conformation, subsite interaction, and hydrogen bonding. The data of geometrical parameters (tau(1), tau(2), and tau(3) listed in Table 2) and root mean square deviation values as compared with the known inhibitor, kni272,(28) show that both kinds of inhibitors interact with HIVPR in a very similar way. The r(2) value of 0.860 indicates that the calculated binding free energies correlate well with the inhibitory activities. The structural and energetic differences in inhibitory potencies of AHPBAs were reasonably explored. Using the binding conformations of AHPBAs, consistent and highly predictive 3D-QSAR models were developed by performing CoMFA, CoMSIA, and HQSAR analyses. The reasonable r(corss)(2) values were 0.613, 0.530, and 0.717 for CoMFA, CoMSIA, and HQSAR models, respectively. The predictive ability of these models was validated by kni272 and a set of nine compounds that were not included in the training set. Mapping these models back to the topology of the active site of HIVPR leads to a better understanding of vital AHPBA-HIVPR interactions. Structural-based investigations and the final 3D-QSAR results provide clear guidelines and accurate activity predictions for novel HIVPR inhibitors. PMID- 11784139 TI - Pyrrolo[1,3]benzothiazepine-based atypical antipsychotic agents. Synthesis, structure-activity relationship, molecular modeling, and biological studies. AB - The prototypical dopamine and serotonin antagonist (+/-)-7-chloro-9-(4 methylpiperazin-1-yl)-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepine (5) was resolved into its R and S enantiomers via crystallization of the diastereomeric tartaric acid salts. Binding studies confirmed that the (R)-(-)-enantiomer is a more potent D(2) receptor antagonist than the (S)-(+)-enantiomer, with almost identical affinity at the 5-HT(2) receptor ((S)-(+)-5, log Y = 4.7; (R)-(-)-5, log Y = 7.4). These data demonstrated a significant stereoselective interaction of 5 at D(2) receptors. Furthermore, enantiomer (S)-(+)-5 (ST1460) was tested on a panel of receptors; this compound showed an intriguing binding profile characterized by high affinity for H(1) and the alpha(1) receptor, a moderate affinity for alpha(2) and D(3) receptors, and low affinity for muscarinic receptors. Pharmacological and biochemical investigation confirmed an atypical pharmacological profile for (S)-(+)-5. This atypical antipsychotic lead has low propensity to induce catalepsy in rat. It has minimal effect on serum prolactin levels, and it has been selected for further pharmacological studies. (S)-(+)-5 increases the extracellular levels of dopamine in the rat striatum after subcutaneous administration. By use of 5 as the lead compound, a novel series of potential atypical antipsychotics has been developed, some of them being characterized by a stereoselective interaction at D(2) receptors. A number of structure-activity relationships trends have been identified, and a possible explanation is advanced in order to account for the observed stereoselectivity of the enantiomer of (+/-)-5 for D(2) receptors. The molecular structure determination of the enantiomers of 5 by X-ray diffraction and molecular modeling is reported. PMID- 11784141 TI - Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity. AB - New amino acids are reported in which component macrocycles are constrained to mimic tripeptides locked in a beta-strand conformation. The novel amino acids involve macrocycles functionalized with both an N- and a C-terminus enabling addition of appendages at either end to modify receptor affinity, selectivity, or membrane permeability. We show that the cycles herein are effective templates within inhibitors of HIV-1 protease. Eleven compounds originating from such bifunctionalized cyclic templates are potent inhibitors of HIV-1 protease (Ki 0.3 50 nM; pH 6.5, I = 0.1 M). Unlike normal peptides comprising amino acids, five of these macrocycle-containing compounds are potent antiviral agents with sub micromolar potencies (IC(50) 170-900 nM) against HIV-1 replication in human MT2 cells. The most active antiviral agents are the most lipophilic, with calculated values of LogD(6.5) > or = 4. All molecules have a conformationally constrained 17-membered macrocyclic ring that has been shown to structurally mimic a tripeptide segment (Xaa)-(Val/Ile)-(Phe/Tyr) of a peptide substrate in the extended conformation. The presence of two trans amide bonds and a para substituted aromatic ring prevents intramolecular hydrogen bonds and fixes the macrocycle in the extended conformation. Similarly constrained macrocycles may be useful templates for the creation of inhibitors for the many other proteins and proteases that recognize peptide beta-strands. PMID- 11784140 TI - Design, synthesis, and preliminary pharmacological evaluation of N-acyl-3 aminoglutarimides as broad-spectrum chemokine inhibitors in vitro and anti inflammatory agents in vivo. AB - A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inhibitory effects. Among the compounds studied, 10 (NR58,4) was the most potent, being active at doses between 5 and 15 nM in vitro and at 0.3 mg kg( 1) in vivo. PMID- 11784142 TI - 2-Amino-3-aroyl-4,5-alkylthiophenes: agonist allosteric enhancers at human A(1) adenosine receptors. AB - 2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5 dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2 amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3 benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A(1)AR agonist [(125)I]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2 amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the (CH(2))(n)()- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5. PMID- 11784143 TI - C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. AB - The P-glycoprotein product (Pgp) of the MDR1 gene has been implicated in the multiple drug resistance phenotype expressed by many cancers. Functioning as an efflux pump, P-glycoprotein prevents the accumulation of high intracellular concentrations of substrates. We have taken a rational approach to designing inhibitors of P-glycoprotein function, selecting a natural substrate (progesterone) as our lead compound. We hypothesized that progesterone, substituted at C-7 with an aromatic moiety(s), would exhibit reduced Pgp affinity, significantly increased antiPgp activity, and reduced affinity for progesterone receptors (PGR). We synthesized 7 alpha-[4'-(aminophenyl)thio]pregna 4-ene-3,20-dione (2), which comprises a C-7 alpha thiol bridge linking an aminophenyl moiety to progesterone, from pregna-4,6-diene-3,20-dione (1). The subsequent addition reaction of 2 with the appropriate isocyanate produced an initial series of compounds (3-6). Compounds 3-5 (respectively, -CH(2)CH(2)Cl; CH(2)CH(3); and -CH(CH(3))C(6)H(5)) exhibit a significantly increased ability to inhibit P-glycoprotein. Potency for restoring doxorubicin accumulation in MDR1 transduced human breast cancer cells is increased up to 60-fold as compared with progesterone. Compound 5 has greater potency than verapamil and is equipotent with cyclosporin A, for inhibiting P-glycoprotein function. Furthermore, 5 does not bind to PGR, implying a potential reduction in in vivo toxicity. These data identify C-7-substituted progesterone analogues and 5, in particular, as rationally designed antiPgp compounds worthy of further evaluation/development. PMID- 11784144 TI - New approach to pharmacophore mapping and QSAR analysis using inductive logic programming. Application to thermolysin inhibitors and glycogen phosphorylase B inhibitors. AB - A key problem in QSAR is the selection of appropriate descriptors to form accurate regression equations for the compounds under study. Inductive logic programming (ILP) algorithms are a class of machine-learning algorithms that have been successfully applied to a number of SAR problems. Unlike other QSAR methods, which use attributes to describe chemical structure, ILP uses relations. This gives ILP the advantages of not requiring explicit superimposition of individual compounds in a dataset, of dealing naturally with multiple conformations, and of using a language much closer to that used normally by chemists. We unify ILP and standard regression techniques to give a QSAR method that has the strength of ILP at describing steric structure with the familiarity and power of regression methods. Complex pharmacophores, correlating with activity, were identified and used as new indicator variables, along with the comparative molecular field analysis (CoMFA) prediction, to form predictive regression equations. We compared the formation of 3D-QSARs using standard CoMFA with the use of ILP on the well studied thermolysin zinc protease inhibitor dataset and a glycogen phosphorylase inhibitor dataset. In each case the addition of ILP variables produced statistically better results (P < 0.01 for thermolysin and P < 0.05 for GP datasets) than the CoMFA analysis. Moreover, the new ILP variables were not found to increase the complexity of the final QSAR equations and gave possible insight into the binding mechanism of the ligand-protein complex under study. PMID- 11784145 TI - Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents. AB - Thirty Schiff bases of hydroxysemicarbazide (Ar-CH=NNHCONHOH) have been synthesized and tested against L1210 murine leukemia cells. The IC(50) values were found to be in a range from 2.7 x 10(-6) to 9.4 x 10(-4) M. A total of 17 out of the 30 compounds had higher inhibitory activities than hydroxyurea (an anticancer drug currently used for the treatment of melanoma, leukemia, and ovarian cancer) against L1210 cells. Six compounds with IC(50) values in micromolar range were 11- to 30-fold more potent than hydroxyurea (IC(50) = 8.2 x 10(-5) M). The partition coefficient (log P) and ionization constants (pK(a)) of a model compound [1-(3-trifluoromethylbenzylidene)-4-hydroxysemicarbazide, 1] were measured by the shake-flask method, and the measured log P was used to derive Hansch-Fujita pi constant of -CH=NNHCONHOH. On the basis of the newly derived pi and those of other moieties, the partition coefficients (SlogP) of the other 29 compounds were calculated by the summation of pi values. Quantitative structure-activity relationship (QSAR) analysis showed that, besides the essential pharmacophore (-NHCONHOH), hydrophobicity (SlogP), molecular size/polarizability (calculated molar refractivity), and the presence of an oxygen-containing group at the ortho position (I) were important determinants for the antitumor activities. In conclusion, the results obtained in this study show that several Schiff bases of hydroxysemicarbazide are potent inhibitors of tumor cells and warrant further investigation as cancer chemotherapeutic agents. PMID- 11784146 TI - 2,5'-Disubstituted adenosine derivatives: evaluation of selectivity and efficacy for the adenosine A(1), A(2A), and A(3) receptor. AB - Novel 2,5'-disubstituted adenosine derivatives were synthesized in good overall yields starting from commercially available guanosine. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and human A(3) receptors. E(max) values were determined for the stimulation or inhibition of cAMP production in CHO cells expressing human adenosine A(2A) (EC(50) values as well) or A(3) receptors, respectively. The compounds displayed affinities in the nanomolar range for both the adenosine A(2A) and A(3) receptor, without substantial preference for either receptor. The derivatives with a 2-(1-hexynyl) group had the highest affinities for both receptors; compound 4 (2-(1 hexynyl)adenosine) had the highest affinity for the adenosine A(2A) receptor with a K(i) value of 6 nM (A(3)/A(2A) selectivity ratio of approximately 3), whereas compound 37 (2-(1-hexynyl)-5'-S-methyl-5'-thioadenosine) had the highest affinity for the adenosine A(3) receptor with a K(i) value of 15 nM (A(2A)/A(3) selectivity ratio of 4). In general, compounds with a relatively small 5'-S-alkyl 5'-thio substituent (methyl-5'-thio) displayed the highest affinities for both the adenosine A(2A) and A(3) receptor; the larger ones (n- or i-propyl-5'-thio) increased the selectivity for the adenosine A(3) receptor. The novel compounds were also evaluated in cAMP assays for their (partial) agonistic behavior. Overall, the disubstituted derivatives behaved as partial agonists for both the adenosine A(2A) and A(3) receptor. The compounds showed somewhat higher intrinsic activities on the adenosine A(2A) receptor than on the A(3) receptor. Compounds 37, 40 and 45, 48, with either a 5'-S-methyl-5'-thio or a 5'-S-i-propyl-5'-thio substituent had the lowest intrinsic activities on the adenosine A(2A) receptor. For the A(3) receptor, compounds 34, 35, 38, 39, and 46, 47, with a 5'-S-ethyl-5' thio or a 5'-S-n-propyl-5'-thio substituent had the lowest intrinsic activities. PMID- 11784147 TI - A new type of mixed anhydride and its applications to the synthesis of 7 substituted 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazines with in vitro antitumor activity. AB - A new series of 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine derivatives 8-25 with heteroaryloxycarbonyl or heteroarylcarbamoyl substituents at position 7 have been synthesized as potential antitumor agents. In this procedure a novel type of mixed anhydride 7 was prepared from 8-chloro-5,5 dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylic acid 6 and methanesulfonyl chloride, which in turn was condensed either with heteroarylamines or heteroarylhydroxy compounds. All the compounds prepared were screened at the National Cancer Institute (NCI) for their activities against a panel of 60 tumor cell lines, and relationships between structure and antitumor activity in vitro are discussed. The amides 8, 10, 12, 13, 21, and ester 25 were inactive, whereas the other compounds exhibited rather moderate activity against one or more human tumor cell lines. The prominent compound with remarkable activity (log GI(50) < 8) and selectivity for the leukemia HL-60(TB) cell line was 2-methyl-8-quinolyl 8 chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylate 24. PMID- 11784148 TI - Novel spiropiperidines as highly potent and subtype selective sigma-receptor ligands. Part 1. AB - A series of spiro[[2]benzopyran-1,4'-piperidines] and spiro[[2]benzofuran-1,4' piperidines] of general structure 10 is prepared, and the affinity for sigma(1)- and sigma(2)-receptors is investigated by means of radioligand binding assays. The synthesis of the spiropiperidines 14a and 23 proceeds from bromine/lithium exchange of the bromoacetals 11 and 21, addition to piperidin-4-one 12a, and subsequent cyclization. Systematic variations of the substituent R at the nitrogen atom, the group X in position 3, and the ring size of the oxygen heterocycle are performed. The sigma(1)- and sigma(2)-receptor affinities are determined with guinea pig brain and rat liver membrane preparations using [(3)H] labeled (+)-pentazocine and ditolylguanidine, respectively. Test results show that a benzyl residue at the piperidine nitrogen atom and a methoxy group in position 3 are advantageous for high sigma(1)-receptor affinity. In this series the 1'-benzyl-3-methoxy-3,4-dihydrospiro[[2]benzopyran-1,4'-piperidine] (14a) and the 1'-benzyl-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine] (23) are among the most potent sigma(1)-ligands interacting in the low nanomolar range with sigma(1)-receptors (14a, K(i) = 1.29 nM; 23, K(i) = 1.14 nM). Variation of the nitrogen substituent R from benzyl to H, alkyl, phenyl, or omega-phenylalkyl and the group X from methoxy to hydroxy, carbonyl, or alkyloxy led to reduced sigma(1)-receptor affinity. In addition to their high sigma(1)-receptor affinity, the spiropiperidines 14a and 23 display excellent selectivity toward sigma(2) receptors (sigma(1)/sigma(2) = 2708 and 1130) and several other receptor and reuptake systems. Introduction of a polar hydroxy group in position 3 and elongation of the distance between the piperidine nitrogen atom and the phenyl moiety result in ligands with considerable sigma(2)-receptor affinity and therefore diminished sigma(1)/sigma(2)-receptor selectivity. The hemiacetalic 1' (3-phenylpropyl)-3,4-dihydrospiro[[2]benzopyran-1,4'-piperidin]-3-ol (15e) represents the most active sigma(2)-receptor ligand in this series with a K(i) value of 83.1 nM. PMID- 11784149 TI - Water-soluble, core-modified porphyrins as novel, longer-wavelength-absorbing sensitizers for photodynamic therapy. II. Effects of core heteroatoms and meso substituents on biological activity. AB - Water-soluble, core-modified porphyrins were prepared and evaluated as sensitizers for photodynamic therapy (PDT). The addition of an aromatic aldehyde to 2,5-dilithiothiophene or -selenophene gave diol 3 as a nearly equimolar mixture of meso and d,l diastereomers, which gave a single diastereomer following careful recrystallization. The condensation of pyrrole with a diol 3 using catalytic BF(3)-etherate gave bispyrrolochalcogenophenes (4). Condensation of a diol 3 with 4 in the presence BF(3)-etherate gave 21,23-dichalcogenaporphyrins (5). 21-Thiaporphyrins (6) were prepared by condensation of a diol 3 with excess pyrrole and benzaldehyde in the presence of tetrachlorobenzoquinone and catalytic BF(3)-etherate. Sulfonation of 5 and 6 with concentrated sulfuric acid at 100 degrees C gave sulfonated derivatives 7-15. Bis-4-methoxy-21,23-dithiaporphyrins 5h and 5l were demethylated with BBr(3), and the resulting phenols were alkylated with ethyl bromoacetate. Saponification gave 21,23-dithiaporphyrin dicarboxylate salts 16 and 17. The 21,23-core-modified porphyrins gave band I absorption maxima (lambda(max) of 689-717 nm) at longer wavelengths than band I for the corresponding 21-core-modified porphyrins, but both classes had band I maxima at longer wavelengths than either TPPS(4) or Photofrin (lambda(max) of 630 nm for both). The core heteroatoms had little effect on either absorption maxima or quantum yields of singlet oxygen generation in 7-17. The meso substituents had a greater impact on absorption maxima. Compounds 7-17 were evaluated for phototoxicity against Colo-26 cells in culture using 4 J cm(-2) of 570-800 nm light. Compounds 8-12, 14, 16, and 17 gave a 50% cell kill in vitro at a lower concentration than Photofrin [5.7 mg (9 micromol)/kg]. Compounds 14, 16, and 17 gave a 50% cell kill with 4 J cm(-2) of light and submicromolar concentrations of sensitizer. Sensitizers 8 and 11 showed no toxicity or side effects in BALB/c mice observed for 90 days following a single intravenous injection of 10 mg/kg of sensitizer. Distribution studies show that sensitizer 8 accumulates in the tumors of BALB/c mice. PDT with 8 at 0.125 mg (0.13 micromol)/kg or 11 at 2.5 mg (2.5 micromol)/kg and 135 J cm(-2) of 694 nm light was comparable to PDT with Photofrin at 2.5 mg (4 micromol)/kg and 135 J cm(-2) of 630 nm light against Colo 26 tumors in BALB/c mice. PMID- 11784150 TI - Synthesis and characterization of a series of novel monoacylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids, as skin antioxidants. AB - A series of novel monoacylated vitamin C derivatives were chemically synthesized with a stable ascorbate derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and acid anhydrides in pyridine. Their solubility in organic phase, thermal stability, radical scavenging activity, and in vitro skin permeability was evaluated. These monoacylated derivatives were identified as 6-O-acyl-2-O alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G) by UV spectra, elemental analyses, and nuclear magnetic resonance spectroscopy. The reactions afforded 6 Acyl-AA-2G in high yields (30-60%). 6-Acyl-AA-2G exhibited satisfactory stability in neutral solution comparable to that of a typical stable derivative, AA-2G, and also showed the radical scavenging activity. The lipid solubility of 6-Acyl-AA-2G was increased with increasing length of their acyl group. Increased skin permeability was superior to those of AA-2G and ascorbic acid (AsA). 6-Acyl-AA-2G that is susceptible to enzymatic hydrolysis by tissue esterase and/or alpha glucosidase produces AA-2G and AsA, which is in the skin tissues. Thus, these findings indicate that the novel vitamin C derivatives presented here, 6-Acyl-AA 2G, may be effective antioxidants in skin care and medicinal use. PMID- 11784151 TI - Radiolabeling and in vivo behavior of copper-64-labeled cross-bridged cyclam ligands. AB - Macrocyclic chelators and their metal complexes have widespread applications in the biomedical sciences, including radiopharmaceutical chemistry. The use of copper radionuclides in radiopharmaceuticals is increasing. Macrocyclic chelators have been found to have enhanced in vivo stability over acyclic chelators such as ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). The currently used chelators of choice for labeling copper radionuclides to biological molecules are analogues of TETA (1,4,8,11-tetraazacyclotetradecane 1,4,8,11-tetraacetic acid); however, recent reports have demonstrated evidence of in vivo instability of the radio-Cu(II)-TETA complexes. A new class of structurally reinforced macrocycles, the "cross-bridged" cyclam derivatives, form highly stable complexes with Cu(II) that are resistant to dissociation in strong acid. Here, we evaluate a series of (64)Cu(II) cross-bridged macrocyclic complexes for biological stability and in vivo behavior. The ligands evaluated include the parent ligand, 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1), and three 4,11-di-pendant arm derivatives: 4,11-bis(carboxymethyl)-1,4,8,11 tetraazabicyclo[6.6.2]hexadecane (2); 4,11-bis(N,N-diethyl-amidomethyl)-1,4,8,11 tetraazabicyclo[6.6.2]hexadecane (3); and 4,11-bis(amidoethyl)-1,4,8,11 tetraazabicyclo[6.6.2]hexadecane (4). Copper-64 formed complexes with ligands 1-4 in high radiochemical yields. The (64)Cu-2 complex was neutral, while (64)Cu complexes of 1, 3, and 4 were positively charged. All complexes showed no decomposition in rat serum out to 24 h. Biodistribution experiments in Sprague Dawley rats indicated that (64)Cu-1, -3, and -4 were taken up by the liver and kidney and cleared slowly over 24 h, whereas (64)Cu-2 cleared rapidly from all tissues. The rapid clearance of the (64)Cu-2 complex from the blood and liver, as well as liver metabolism experiments in rats, suggests that it is highly stable in vivo. A bifunctional chelator of 2 is a significant candidate for labeling copper radionuclides to biological molecules for diagnostic imaging and targeted radiotherapy. PMID- 11784152 TI - Structure-activity profiles of complex biantennary glycans with core fucosylation and with/without additional alpha 2,3/alpha 2,6 sialylation: synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake. AB - The consideration of oligosaccharides and glycoconjugates as biopharmaceuticals is an emerging topic in drug design. Chemoenzymatic synthesis of N-glycans was performed to examine the influence of N-glycan core fucosylation on lectin binding properties and biodistribution. As a first step in a systematic comparison of N-glycans, the core fucose moiety was chemically introduced into a complex-type biantennary heptasaccharide azide. After deprotection and attachment of a spacer, the terminal sections of the N-glycan were elongated enzymatically. Conversion of the amino group in the spacer to an isothiocyanate gave derivatives allowing convenient ligand attachment to bovine serum albumin (BSA). The resulting neoglycoproteins contained an average of 2.9-4.6 chains per carrier molecule. Relative to unsubstituted biantennary complex-type N-glycans, the core fucosylation appears to favor the extended orientation of the alpha 1,6-arm. This was deduced from an up to 5-fold alteration of affinity for lectins in solid phase assays. Marked differences were also found for cell surface binding of cultured tumor cells, for staining of tumor cells in lung sections, and in organ distribution. In vivo, the alpha 2,6-sialylated neoglycoproteins showed a reduced serum half-life in mice relative to the alpha 2,3-sialylated isomer and the non fucosylated congeners. These results support the notion that changing the shape of a glycan provides a promising strategy to optimize the affinity of protein carbohydrate interactions. Overall, our study underscores the importance of chemoenzymatic synthesis to define the effect of chain orientation on the ligand properties of N-glycans. PMID- 11784154 TI - Carbonic anhydrase activators: design of high affinity isozymes I, II, and IV activators, incorporating tri-/tetrasubstituted-pyridinium-azole moieties. AB - A series of tight binding carbonic anhydrase (CA) activators was obtained by reaction of amino-azoles (3-amino-pyrazole, 2-amino-imidazole, and 5-amino tetrazole) with tri- or tetrasubstituted pyrylium salts. Many of the new pyridinium salts incorporating azole moieties reported here proved to be efficient in vitro activators of three CA isozymes, CA I, II, and IV. Very good activity was detected against hCA I and bCA IV (h = human; b = bovine isozymes), for which some of the new compounds showed affinities in the low nanomolar range, whereas against hCA II, their affinities were in the range of 95-150 nM. Substitution patterns of the pyridinium ring leading to best activity included 4 phenyl-2,6-dialkyl moieties or 2,4,6-tri- and 2,3,4,6-tetraalkyl groups. Ex vivo experiments showed some of the new activators to strongly enhance CA activity after incubation with human erythrocytes. Furthermore, due to their cationic nature, some of these compounds (the imidazole and pyrazole derivatives) are membrane-impermeant, discriminating thus between cytosolic and membrane-bound CA isozymes. The present paper is the first report of membrane-impermeant CA activators. The pyridinium tetrazole derivatives on the other hand do penetrate through biological membranes. Such CA activators might lead to the development of drugs/diagnostic tools for the management of CA deficiency syndromes as well as for the pharmacological enhancement of synaptic efficacy, spatial learning, and memory. This may constitute a new approach for the treatment of Alzheimer disease and other conditions in need of achieving memory therapy. PMID- 11784153 TI - 4-(Phenylsulfonyl)piperidines: novel, selective, and bioavailable 5-HT(2A) receptor antagonists. AB - On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identified as high-affinity, selective 5-HT(2A) receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4 (phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound. PMID- 11784155 TI - Orally-effective, long-acting sorbitol dehydrogenase inhibitors: synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle substituted piperazino-pyrimidines. AB - Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED(90) < or = 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED(90) values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day. PMID- 11784156 TI - Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). AB - Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the sponge Stylissa massa afforded eight known alkaloids: aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC(50) 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells. PMID- 11784157 TI - Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors. AB - New CA(1)A(2)X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heterocycles, taking into account the role of zinc and the metabolic instability of amino acids. The molecular docking of 8 in the active site of the enzyme and the pharmacological evaluation of the compounds are illustrative of a new class of FTIs. PMID- 11784158 TI - 4'-Arylpyrrolomorphinans: effect of a pyrrolo-N-benzyl substituent in enhancing delta-opioid antagonist activity. AB - A new method for the preparation of N-benzylpyrrolomorphinans has been developed. Thus Michael reaction of the benzylimines of oxycodones and oxymorphones with nitrostyrenes gave a series of 4'-aryl-N-benzylpyrrolomorphinans. These were selective delta antagonists of much higher in vitro potency (with 5a having K(e) delta = <1 nM) than their binding affinities predicted. In mice in vivo assays 5a showed good delta antagonist activity in the anti-writhing analgesic assay and also inhibited delta agonist-induced convulsant activity. PMID- 11784159 TI - Hybridization between "six-membered" nucleic acids: RNA as a universal information system. AB - Within the polyA:polyT recognition system, cross-pairing between several nucleic acids with a phosphorylated six-membered carbohydrate (mimic) as repeating unit in the backbone structure has been observed. All investigated nucleic acids (except for beta-homo-DNA) hybridize with RNA, leaving RNA as a versatile biopolymer for informational transfer. [reaction: see text] PMID- 11784160 TI - Conformational preference and remote (1,10) stereocontrol in biphenyl-2,2' dicarboxamides. AB - The double ortholithiation and electrophilic quench of N,N,N'N' tetraisopropylbiphenyl-2,2'-dicarboxamide 1 is diastereoselective, giving the chiral, C(2)-symmetric atropisomers of the 3,3'-disubstituted products 3. These chiral atropisomers can be converted with moderate to good stereoselectivity to their achiral, centrosymmetric epimers by heating. The stereoselectivity of the double lithiation-quench reaction is determined by the stereochemistry of the intermediate doubly lithiated species 2, either diastereoisomer of which may be formed stereospecfically from the corresponding atropisomeric dibromo compounds.[reaction: see text] PMID- 11784161 TI - A theoretical study of the chorismate synthase reaction. AB - Density functional calculations (B3LYP/6-31+G(d,p)) were carried out to investigate the mechanism of the anti-1,4-elimination of phosphate from 5 enolpyruvylshikimate-3-phosphate 1 that is catalyzed by chorismate synthase. Of particular interest was the functional role of the reduced flavin cofactor. [reaction: see text] PMID- 11784162 TI - Partial aminomethylation of resorcarenes. AB - Aminomethylation of resorcarenes at the wider rim with bulky diisopropylamine and formaline leads to trisubstituted derivatives. Analogous reaction with C(2v) symmetrical resorcarene tetratosylate gives the monoaminomethylated compound. Further reactions of remaining unsubstituted resorcinol rings result in new resorcarene derivatives. [reaction: see text] PMID- 11784163 TI - Selective cleavage of Cbz-protected amines. AB - Under conditions of catalytic Ni(0) and in most cases just over 1 equiv of Me(2)NH.BH(3)/K(2)CO(3) or Cs(2)CO(3), a Cbz-protected nitrogen, which is part of a heteroaromatic ring, can be chemospecifically cleaved without affecting a Cbz group on an originally basic amine. [reaction: see text] PMID- 11784164 TI - An efficient synthesis of morpholin-2-one derivatives using glycolaldehyde dimer by the Ugi multicomponent reaction. AB - A new one-pot procedure for the efficient synthesis of novel 3-substituted morpholin-2-one-5-carboxamide derivatives using commercially available glycolaldehyde dimer as a bifunctional component with various alpha-amino acids and isocyanides by the Ugi five-center three-component reaction (U-5C-3CR) was developed. [reaction: see text] PMID- 11784165 TI - Enantioselective intramolecular aromatic [4 + 4] photocycloaddition in crystalline state: parameters for reactivity. AB - Photoreactivity of seven 9-anthryl-N-(naphthylcarbonyl)carboxamide derivatives, 1a-g, in their intramolecular [4 + 4] photocycloadditions in solid state is discussed on the basis of their single-crystal X-ray analyses. The distances (d(1) and d(2)) between the two carbon atoms to be reacted, the angles (theta(1) and theta(2)), and the torsion angle (theta(3)) between the anthracene and naphthalene rings were chosen as structural parameters for reactivity. For 1a and 1e, the first example of absolute asymmetric synthesis in [4 + 4] photocycloaddition was attained. [reaction: see text] PMID- 11784166 TI - Subtilisin-catalyzed synthesis of amino acid and peptide esters. Application in a two-step enzymatic ligation strategy. AB - We describe an efficient enzymatic approach to the synthesis of amino acid and peptide esters. The serine protease subtilisin Carlsberg (EC 3.4.21.62) was found to efficiently catalyze the specific formation of C(alpha)-carboxyl 3 hydroxypropyl or 4-hydroxybutyl esters of certain Boc-amino acids and peptides in high-content 1,3-propanediol or 1,4-butanediol solution, with substrate specificity parallel to that of the normal hydrolytic reaction. This approach can be coupled with kinetic-control reverse proteolysis in a two-step enzymatic peptide ligation scheme. [reaction: see text] PMID- 11784167 TI - Diastereoselective synthesis of 2H,5H-dihydrofurans by cobalt-mediated cycloisomerization of allyl propargyl ethers. Application to poly-THF molecules. AB - Allyl propargyl ethers undergo cobalt-mediated cycloisomerization reactions to form dihydrofurans in good yield and with excellent diastereoselectivity. The reaction works with a range of substrates, and its utility in synthesis is exemplified by the preparation of a bistetrahydrofuran unit. [reaction: see text] PMID- 11784168 TI - A new type of lycopodium alkaloid, lycoposerramine-A, from Lycopodium serratum Thunb. AB - A novel alkaloid, lycoposerramine-A (1), which has a 1,2,4-oxadiazolidin-5-one residue in the molecule, was isolated from the club moss Lycopodium serratum Thunb. The structure was determined by spectroscopic and X-ray analyses. [structure: see text] PMID- 11784169 TI - Tandem chain extension-aldol reaction: syn selectivity with a zinc enolate. AB - A tandem chain extension-aldol reaction was developed in which beta-keto esters are transformed to alpha-substituted-gamma-keto esters in an efficient zinc mediated, one-pot reaction. The diastereoselectivity of the reaction ranged from good to excellent with syn stereochemistry observed for beta-keto ester and amide substrates and anti-stereochemistry observed for a beta-keto imide. [reaction: see text] PMID- 11784170 TI - Stille couplings catalytic in tin: a "Sn-F" approach. AB - A new tin recycling method for Stille couplings catalytic in tin is reported. PMHS made hypercoordinate by KF((aq)) allows Me(3)SnH to be efficiently recycled during a Pd(0)-catalyzed hydrostannation/Stille cascade. Relative to previously disclosed protocols, reaction times are shorter and because this process is believed to proceed through a Me(3)SnF intermediate the hazards and problems associated with trimethyltins are also diminished.[reaction: see text] PMID- 11784171 TI - Synthesis and potent anti-HIV activity of L-3'-fluoro-2',3'-unsaturated cytidine. AB - L-2',3'-Didehydro-2',3'-dideoxy-3'-fluorocytidine (L-3'-Fd4C), a novel potent anti-HIV agent (EC(50) 0.03 microM in PBM cells), has been synthesized from L xylose in 14 steps. [reaction: see text] PMID- 11784172 TI - Enantioselective conjugate addition of hydroxylamines to pyrazolidinone acrylamides. AB - Chiral relay templates provide amplification of selectivity in conjugate addition reactions. Reversal of stereochemistry of the product isoxazolidinones has also been demonstrated by a simple change of the Lewis acid. [reaction: see text] PMID- 11784173 TI - Use of iodoacetylene as a dipolarphile in the synthesis of 5-iodoisoxazole derivatives. AB - Iodoacetylene 1 was prepared in situ from the reactions of ethynylmagnesium bromide or tributyl(ethynyl)tin with iodine. It was used as a dipolarphile in the [2 + 3] cyclization reaction with 1,3-dipolar nitrile oxide derivatives to produce 2-(5-iodoisoxazol-3-yl)pyridine 2 and 3-(4-fluorophenyl)-5-iodoisoxazole 8 in good yield (70-90%). Subsequently, several 5-substituted isoxazole derivatives 3 were obtained by Pd-catalyzed reactions. [reaction: see text] PMID- 11784174 TI - Application of Lewis acid catalyzed tropone [6+4] cycloadditions to the synthesis of the core of CP-225,917. AB - The carbocyclic core of CP-225,917 and CP-263,114 is accessible through the [6+4] cycloaddition of a tropone with a 2-substituted cyclopentadiene. Examination of this reaction has revealed for the first time that this cycloaddition process is catalyzed by Lewis acids, including lanthanide triflates. Cycloadditions of several mono-, di-, and trisubstituted tropones with 2-silyloxycyclopentadienes using ZnCl(2) catalysis are found to proceed in good yield and, in many cases, with excellent diastereoselectivity. Subsequent transformation to the core of the CP-molecules involves a site-selective Baeyer-Villiger oxidation of a tricyclic diketone, followed by a syn-elimination process. [reaction: see text] PMID- 11784175 TI - A new route to spiropyrrolidinyl-oxindole alkaloids via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]-2-oxindoles. AB - A new approach for the synthesis of spiropyrrolidinyloxindole alkaloids, i.e. coerulescine (4) and horsfiline (5) has been developed via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]oxindoles 2 to the respective spiropyrroline-2-oxindole derivatives 3 and their subsequent one-pot reductive dethiomethylation-N-methylation. [reaction: see text] PMID- 11784176 TI - Synthesis of substituted-(l)-tryptophanols from an enantiomerically pure aziridine-2-methanol. AB - Enantiomerically pure (l)-tryptophanol (5) was synthesized from 4(R)-iodomethyl-2 oxazolidinone (2) and indolylmagnesium bromide in three steps (52% overall yield). Using this procedure, we also prepared various tryptophanols with substituent(s) on the indole ring. Furthermore, optically active 4(R)-iodomethyl 2-oxazolidinone was readily prepared from an enantiomerically pure aziridine-2(S) methanol in high yield. [reaction: see text] PMID- 11784177 TI - Thioglycosides protected as trans-2,3-cyclic carbonates in chemoselective glycosylations. AB - Thioglycosides protected as trans-2,3-cyclic carbonates have significantly lower anomeric reactivities than fully acylated and N-acyl-protected thioglycosides and can be used as acceptors in chemoselective glycosylations with a wide range of thioglycosyl donors. The resulting thioglycosides can be further activated to give 1,2-cis-linked glycosides. [reaction: see text] PMID- 11784178 TI - Rapid entry to enantiopure carbacepham derivatives via Lewis acid promoted carbonyl-ene cyclization of 2-azetidinone-tethered alkenylaldehydes. AB - Lewis acid promoted types I and II carbonyl-ene cyclizations of 2-azetidinone tethered alkenylaldehydes are used for the rapid, highly diastereoselective synthesis of polyfunctionalized, enantiomerically pure carbacepham derivatives. [reaction: see text] PMID- 11784179 TI - Highly efficient and catalytic conversion of aldoximes to nitriles. AB - Catalytic dehydration of aldoximes can be performed highly efficiently with a catalyst system of [RuCl(2)(p-cymene)](2)/molecular sieves under essentially neutral and mild conditions, and various types of cyano compounds are produced in good to excellent yields. [reaction: see text] PMID- 11784180 TI - Synthesis of meso-meso linked hybrid porphyrin arrays by Pd-catalyzed cross coupling reaction. AB - meso-meso linked porphyrin arrays of a variety of compositions and connectivities have been prepared by Pd-catalyzed cross-coupling reaction in a manner complementary to Ag(I)-promoted oxidative coupling. [reaction: see text] PMID- 11784181 TI - Total synthesis of (+/-)-martinellic acid. AB - A 14-step synthesis of martinellic acid (1) that proceeds in 3% overall yield has been completed using the reaction of aniline 11 with Meldrum's acid-activated vinylcyclopropane 4 to give vinyl pyrrolidinone 12, condensation of aldehyde 13 with N-benzylglycine to form an azomethine ylide that cyclizes to give 14, selective reduction of 14 to amino alcohol 16 with LiBH(4) and MeOH, and guanidine formation by reaction of a cyanamide with 3-methyl-2-buten-1-amine in hexafluoro-2-propanol at 120 degrees C as key steps. [structure: see text] PMID- 11784182 TI - Synthesis of C8-adenosine adducts of arylamines using palladium catalysis. AB - We employed palladium-catalyzed coupling procedures for the synthesis of new C8 adenosine adducts of various arylamines (aniline, benzidine, 4-aminobiphenyl, and 2-aminofluorene).[reaction: see text] PMID- 11784183 TI - NMR separation of beta-prochiral protons to the ether oxygen of chiral esters with lanthanide shift reagents. AB - The use of chiral ester derivatives of 2-phenylethan-1-ol in conjunction with chiral lanthanide shift reagents allows separation of the prochiral and homo prochiral protons to the ether oxygen in the NMR spectrum. Specifically the alpha and beta- protons of the N-(4-nitrophenylsulfonyl)-L-phenylalanyl ester of 2 phenylethan-1-ol, after addition of either europium d- or l-3 heptafluorobutyrylcamphorate or ytterbium d-3-heptafluorobutyrylcamphorate are differentiated. This is the first report of the NMR separation of prochiral protons beta to an ester linkage. [reaction: see text] PMID- 11784184 TI - p-octiphenyl beta-barrels with ion channel and esterase activity. AB - Design, synthesis, and esterase and ion channel activity of a novel barrel-stave supramolecule with hydrophobic exterior and histidine-rich interior are reported. Voltage-dependent binding of pyrenyl-8-oxy-1,3,6-trisulfonates by histidines within p-octiphenyl beta-barrels (and not monomers) via ionic (and not hydrophobic) interactions (K(D), K(I), K(M) < 1 microM) is the basis for superb esterolytic proficiency up to (k(cat)/K(M))/k(uncat) = 9.6 x 10(5) in water and bilayer membranes. The conductance of labile ion channels formed in planar bilayer membranes is shown to be reduced by 8-hydroxypyrene-1,3,6-trisulfonate on the single- and multichannel level. [reaction: see text] PMID- 11784185 TI - Nickel-catalyzed highly regio- and chemoselective cocyclotrimerization of propiolates with allenes: a novel route to polysubstituted benzene derivatives. AB - The Ni(dppe)Br(2)/Zn system effectively catalyzes the cocyclotrimerization of propiolates with allenes. The reaction is highly regio- and chemoselective to afford polysubstituted benzene derivatives in good to excellent yields. [reaction: see text] PMID- 11784186 TI - Chromium vinylidene carbenoids: stereospecific synthesis of (Z)-2-chloroalk-2-en 1-ols. AB - (Z)-2-Chloroalk-2-en-1-ols are obtained in excellent yields from a wide variety of aldehydes by addition of (E)-chromium vinylidene carbenoids, stereospecifically generated from trichloroalkanes using CrCl(2) in THF at room temperature. [reaction: see text] PMID- 11784187 TI - Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. AB - Seventy-two hundred potential inhibitors of the histone deacetylase (HDAC) enzyme family, based on a 1,3-dioxane diversity structure, were synthesized on polystyrene macrobeads. The compounds were arrayed for biological assays in a "one bead-one stock solution" format. Metal-chelating functional groups were used to direct the 1,3-dioxanes to HDAC enzymes, which are zinc hydrolases. Representative structures from this library were tested for inhibitory activity and the 1,3-dioxane structure was shown to be compatible with HDAC inhibition. [structure: see text] PMID- 11784188 TI - The first atisane diterpenoids from a liverwort: polyols from Lepidolaena clavigera. AB - Two new diterpenoids were isolated from the New Zealand liverwort Lepidolaena clavigera. Spectroscopic studies identified the structures as atisanes 1 and 2, with an unprecedented level of oxygenation. This is the first report of the atisane skeleton from a liverwort. Compound 2 showed cytotoxic and insecticidal activity. [structure: see text] PMID- 11784189 TI - Highly selective synthesis of heterosubstituted aromatic sulfamides. AB - The sulfamide functional group is increasingly relevant in both medicinal and supramolecular chemistry, yet few selective synthetic steps are available for its elaboration. We report here a mild, general, and efficient method for the selective differentiation of N-atom substituents of aromatic sulfamides. [reaction: see text] PMID- 11784190 TI - Enantioselective 1,4-addition of unmodified ketone catalyzed by a bimetallic Zn Zn-linked-BINOL complex. AB - 1,4-Addition (Michael addition) of 2-hydroxy-2'-methoxyacetophenone (2) to various alpha,beta-unsaturated ketones was efficiently promoted by a bimetallic Zn-Zn-linked-BINOL complex 3 with good yield (up to 90%) and excellent enantiomeric excess (up to 99% ee). The resulting 2-hydroxy-1,5-diketones were successfully converted to synthetically more versatile esters and amides. [reaction: see text] PMID- 11784191 TI - A practical six-step synthesis of (S)-camptothecin. AB - An asymmetric synthesis of (S)-camptothecin (1) has been accomplished in six steps starting from two commercially available heterocycles. [reaction: see text] PMID- 11784192 TI - New applications of bis(oxazoline) ligands in catalysis: asymmetric 1,2- and 1,4 addition of ZnR(2) to carbonyl compounds. AB - The enantioselective addition of ZnR(2) to aldehydes (1,2) and cyclic enones (1,4) was accomplished using bis(oxazolines) as chiral ligands. The requirement for hydroxymethylene side chains in the ligands strongly suggests that bimetallic catalysts are decisive for high enantiocontrol in these additions. [structure: see text] PMID- 11784193 TI - Convenient synthesis and transformation of 2,6-dichloro-4-iodopyridine. AB - We describe a convenient scalable synthesis of 2,6-dichloro-4-iodopyridine and demonstrate its utility by stepwise elaboration to a number of 2,4,6 trisubstituted pyridines. [reaction: see text] PMID- 11784194 TI - Novel transformations of gamma-silyl nitro compounds. AB - Introduction of a gamma-silyl group into nitro compounds of dihydrobenzofuran, dihydrobenzo[b]thiophene, and dihydrofuran allowed new transformations to take place in the presence of a Lewis acid to give the corresponding alpha,beta unsaturated oximes or multisubstituted dihydrofurans, respectively, in good to excellent yields.[reaction: see text] PMID- 11784195 TI - Nucleophilic trifluoromethylation using trifluoromethyl iodide. A new and simple alternative for the trifluoromethylation of aldehydes and ketones. AB - A novel method for nucleophilic trifluoromethylation of aldehydes and ketones, based on photoinduced reduction of trifluoromethyl iodide by tetrakis(dimethylamino)ethylene (TDAE), is presented. [reaction: see text] PMID- 11784196 TI - Unusual influence of substituents on ring-opening metathesis reactions. AB - The ring-opening cross-metathesis of oxabicyclo[3.2.1]octene derivatives provides a convenient method for preparing differentially substituted 4-pyrones. The major competing reaction is the ring-opening metathesis polymerization of the bridged olefin. Studies on this reaction have shown that substituents on the bicyclic alkene can have a dramatic influence on the competing reactions. [reaction: see text] PMID- 11784197 TI - 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) and microwave-accelerated green chemistry in methylation of phenols, indoles, and benzimidazoles with dimethyl carbonate. AB - 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is a novel and active catalyst in promoting the methylation reaction of phenols, indoles, and benzimidazoles with dimethyl carbonate under mild conditions. Additional rate enhancement is accomplished by applying microwave irradiation. By incorporating tetrabutylammonium iodide, the same microwave reactions can be further accelerated. By combining these acceleration strategies, very slow chemical transformations that take up to several days can be performed efficiently in high yield within minutes. [reaction: see text] PMID- 11784198 TI - Synthesis of 3,4-ethylenedioxyselenophene (EDOS): a novel building block for electron-rich pi-conjugated polymers. AB - A multistep synthesis of the electron-rich 3,4-ethylenedioxyselenophene (EDOS) monomer is described. The electrochemical properties as well as the electropolymerization of EDOS are presented. [structure: see text] PMID- 11784199 TI - Asymmetric synthesis of (+)-hypusine. AB - Wittig reaction of (triphenylphosphoranylidene)acetonitrile with the lactone carbonyl of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4 oxazin-2-one (3) and subsequent reduction generates morpholinylethylamine dihydrochloride (5) in quantitative yield and with excellent diastereoselectivity. Compound 5 was readily converted into hypusine dihydrochloride (1.2HCl) in overall 53% yield. [reaction: see text] PMID- 11784200 TI - Syntheses and absolute stereochemistries of UPA0043 and UPA0044, cytotoxic antibiotics having a p-quinone-methide structure. AB - The first syntheses of new antibiotics UPA0043 and UPA0044 were accomplished starting from commercially available 18beta-glycyrrhetinic acid and vanillin. The present syntheses involve the coupling of a sesquiterpenoid aldehyde and an aryllithium, the stereoselective formation of a p-quinone-methide system, and regioselective intramolecular cyclization via an epoxy ring opening. [reaction: see text] PMID- 11784201 TI - Air-stable trialkylphosphonium salts: simple, practical, and versatile replacements for air-sensitive trialkylphosphines. Applications in stoichiometric and catalytic processes. AB - Trialkylphosphines furnish unusual, sometimes unique, reactivity in a range of transformations. Unfortunately, their utility is compromised by their sensitivity to oxidation. We have examined a simple but powerful strategy for addressing this problem: convert air-sensitive trialkylphosphines into air-stable phosphonium salts via protonation on phosphorus. These robust salts serve as direct replacements for the corresponding phosphines (simple deprotonation under the reaction conditions by a Bronsted base liberates the trialkylphosphine) in a diverse set of applications. [reaction: see text] PMID- 11784202 TI - A pentaerythritol-based molecular scaffold for solid-phase combinatorial chemistry. AB - A convergent synthesis has been developed for the preparation of solid-phase bound construct 1, consisting of an orthogonally protected trifunctional core structure that is attached to TentaGel via a photocleavable linker. [structure: see text] PMID- 11784203 TI - Rhodium-catalyzed regioselective olefin hydrophosphorylation. AB - Parameters influencing the selectivity of the (PPh(3))(3)RhCl-catalyzed hydrophosphorylation of olefins and enynes are described. The reaction between differentiated dienes was shown to be highly responsive to olefin substitution. The trimethylsilyl group effectively reversed the normal preference for hydrophosphorylation of an alkyne over an alkene. [reaction: see text] PMID- 11784204 TI - Intramolecular allenolate acylations in studies toward a synthesis of FR182877. AB - During our efforts to synthesize the cytotoxic natural product FR182877, we discovered intramolecular reductive acylations that offer a stereocontrolled alternative to the classical Knoevenagel condensation for the formation of alpha alkylidene beta-keto-delta-lactones. Other progress toward a synthesis of FR182877 includes a pi-allyl Stille coupling and a bromo Horner-Wadsworth-Emmons reaction that forms a 12-membered ring. Structural relationships among FR182877, hexacyclinic acid, macquarimicin A, and cochleamycin A are also discussed. [reaction: see text] PMID- 11784205 TI - A synthetic pentasaccharide with GTPase activity. AB - The design, synthesis, and preliminary evaluation of the first example of synthetic pentasaccharide (1) that shows marked rate enhancement and specificity for the hydrolysis of GTP to GDP and orthophosphate (OP) are reported. At the concentration ratios of GTP/1 = 3.6 and GTP/Mg(2+) = 1 (pH 7.1, 50 degrees C), a rate enhancement of about 500-fold was obtained.[reaction: see text] PMID- 11784206 TI - Formation of aryl-nitrogen, aryl-oxygen, and aryl-carbon bonds using well-defined copper(I)-based catalysts. AB - We report mild synthetic protocols for the formation of aryl-carbon, aryl nitrogen, and aryl-oxygen bonds based on soluble, well-defined copper(I) catalysts. These protocols do not require the use of palladium and/or expensive ligands. [structure: see text] PMID- 11784207 TI - Direct addition of TMS-acetylene to aldimines catalyzed by a simple, commercially available Ir(I) complex. AB - A new, convenient procedure for the addition reaction of trimethylsilylacetylene to imines is described. Simply treating a solution of aldimine and trimethylsilyl acetylene with catalytic [IrCl(COD)](2) furnishes the adduct in preparatively useful yields. Interestingly, the reaction may be conducted in the absence of solvent. [reaction: see text] PMID- 11784208 TI - A simple biomimetic synthesis of styelsamine B. AB - An extremely rapid, low cost, and environmentally friendly entry into the pyridoacridine family of alkaloids has been devised, as demonstrated here by the first total synthesis of styelsamine B (3) and its oxidation to the quinoneimine cystodytin J (4). The known reaction of cystodytin J with methanethiol makes this a formal synthesis of diplamine. [reaction: see text] PMID- 11784210 TI - Therapy with proteolytic enzymes in rheumatic disorders. AB - Plant extracts with a high content of proteolytic enzymes have been used in traditional medicine for a long time. Besides herbal proteinases, 'modern' enzyme therapy includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is empirically based, but is also supported by scientific studies. This review provides an overview of preclinical and clinical trials of systemic enzyme therapy in rheumatic disorders. Studies of the use of proteolytic enzymes in rheumatic disorders have mostly been carried out on enzyme preparations consisting of combinations of bromelain, papain, trypsin and chymotrypsin. The precise mechanism of action of systemic enzyme therapy remains unresolved. The ratio of proteinases to antiproteinases, which is affected by rheumatic diseases, appears to be influenced by the oral administration of proteolytic enzymes, probably via induction of the synthesis of antiproteinases or a signal transduction of the proteinase-antiproteinase complex via specific receptors. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes resulting from immunomodulatory effects, which might be an indication of the efficacy of enzyme therapy. The results of various studies (placebo-controlled and comparisons with nonsteroidal anti inflammatory drugs) in patients with rheumatic diseases suggest that oral therapy with proteolytic enzymes produces certain analgesic and anti-inflammatory effects. However, the results are often inconsistent. Nevertheless, in the light of preclinical and experimental data as well as therapeutic experience, the application of enzyme therapy seems plausible in carefully chosen patients with rheumatic disorders. PMID- 11784211 TI - Coxsackie B virus infection in idiopathic dilated cardiomyopathy: clinical and pharmacological implications. AB - Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC. PMID- 11784212 TI - Current management of primary pulmonary hypertension. AB - Primary pulmonary hypertension (PPH) is a rare disorder of the lung vasculature characterised by an increase in pulmonary artery pressure. Although the aetiology of this disease remains unknown, knowledge of the pathophysiology of the disease has advanced considerably. Diagnosis of PPH is largely by exclusion. The clinical symptoms associated with PPH are aspecific and similar to those seen in other cardiovascular and pulmonary diseases. Electrocardiography, echocardiography, pulmonary function tests, and a lung perfusion scan are necessary to exclude secondary forms of pulmonary hypertension and also help to confirm the diagnosis of PPH. A definite diagnosis of PPH is established by right-heart catheterisation which gives a precise measure of the blood pressure in the right side of the heart and the pulmonary artery, right ventricular function and cardiac output. Once a diagnosis of PPH is established, treatment involving drug therapy or surgery is commenced on the basis of the New York Heart Association functional class. Conventional treatment consists of lifetime administration of anticoagulants, oxygen, diuretics, and digoxin. Vasodilator therapy with calcium channel antagonists is indicated in patients who are 'vasoreactive' to acute vasodilator challenge as assessed by right-heart catheterisation. Promising results are obtained by continuous intravenous administration of epoprostenol (prostacyclin). Newer therapies for PPH include prostacyclin analogues, endothelin receptor antagonists, nitric oxide, phosphodiesterase-5 inhibitors, elastase inhibitors, and gene therapy. Surgical treatment consists of atrial septostomy, thromboendarterectomy, and lung or heart-lung transplantation. PMID- 11784213 TI - Innovative cancer vaccine strategies based on the identification of tumour associated antigens. AB - The identification of tumour-associated antigens has opened up new approaches to cancer immunotherapy. While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against cancer. In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in cancer immunotherapy. The cloning of MHC class I- or class II-associated antigens has made it possible to develop synthetic and recombinant cancer vaccines that express specific tumour antigens. There are three major types of synthetic and recombinant cancer vaccines: recombinant viral and bacterial vaccines; naked DNA or RNA vaccines; and recombinant protein and peptide vaccines. In this article, we also discuss a new generation of recombinant cancer vaccines, 'self-replicating' DNA and RNA vaccines. Studies on the mechanisms of 'self-replicating' nucleic acid vaccines revealed that the enhanced immunogenicity was not due to an enhanced antigen expression, suggesting that the quantitative difference may not be as important as the qualitative difference in antigen presentation. The presence of the RNA replicase in the 'self-replicating' nucleic acid vaccines mimics alphavirus infection, which triggers the innate antiviral pathways of the host cells. Studies on how viral and cellular modulators of the innate antiviral pathways affect vaccine function should provide molecular insights crucial to future vaccine design. PMID- 11784214 TI - Current and future applications of immunological attenuation via pegylation of cells and tissue. AB - Prevention of immunological rejection of transplanted tissues is of crucial importance in transplantation medicine. Current procedures primarily use pharmacological agents such as cyclosporin, which, while effective, must be typically administered for the life of the individual. Furthermore, the drug induced global immunosuppression of the patient predisposes the individual to infection and enhances their risk of developing certain forms of cancer. Hence, additional methods are needed to both enhance tissue engraftment and diminish the adverse effects of current immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised form of cellular transplantation) suggest that covalent modification of cells and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish rejection episodes and may further enhance the induction of tolerance to donor tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss of antigen recognition, impaired cell-cell interaction, and an inability of endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind foreign epitopes. As a consequence of the global camouflage imparted by mPEG, the weak co-stimulation of alloreactive T cells may subsequently induce apoptosis, thus leading to tolerance. Initial studies on the transplantation of pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation does not impair in vivo cellular signalling and function. Thus, in contrast to the pharmacological inhibition of the recipient's immune response, the mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and immunogenicity of the donor tissue itself while leaving the recipient a fully competent immune system. PMID- 11784215 TI - The effect of antidepressant treatment on chronic back pain: a meta-analysis. AB - BACKGROUND: Back pain is one of the most common problems in primary care. Antidepressant medication is often prescribed, especially for chronic back discomfort, to alleviate pain and restore the patient's ability to conduct activities of daily living. OBJECTIVE: To assess the efficacy of antidepressants in treating back pain in adults. METHODS: We searched the MEDLINE (1966-2000), PsycLit, Cinhal, EMBASE, AIDSLINE, HealthSTAR, CANCERLIT, the Cochrane Library (clinical trials registry and the Database of Systematic Reviews), Micromedex, and Federal Research in Progress databases and references of reviewed articles. Included articles were written in English and dealt with randomized placebo controlled trials of antidepressant medication use among adults with chronic back pain. Two reviewers abstracted data independently. Two continuous outcomes, change in back pain severity and ability to perform activities of daily living, were measured. Study quality was assessed with the methods used by Jadad and colleagues, and data were synthesized using a random-effects model. RESULTS: Nine randomized controlled trials with 10 treatment arms and 504 patients were included. Seven treatment arms included patients with major depression. Patients had chronic back pain, averaging 10.4 years. Patients treated with antidepressants were more likely to improve in pain severity than those taking placebo (standardized mean difference, 0.41; 95% confidence interval, 0.22-0.61) but not in activities of daily living (standardized mean difference, 0.24; 95% confidence interval, -0.21-0.69). Patients treated with antidepressants experienced more adverse effects (22% vs 14%, P =.01) than those receiving placebo. CONCLUSION: Antidepressants are more effective than placebo in reducing pain severity but not functional status in chronic back pain. PMID- 11784216 TI - Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. AB - BACKGROUND: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available. METHODS: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors. RESULTS: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94). CONCLUSIONS: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days. PMID- 11784217 TI - Fractures between the ages of 20 and 50 years increase women's risk of subsequent fractures. AB - BACKGROUND: Perimenopausal and postmenopausal fractures are well-recognized, strong, independent predictors of subsequent fractures. However, it is unknown whether premenopausal fractures are predictive of postmenopausal fractures. OBJECTIVE: To determine whether self-reported fractures sustained before the age of 50 years are associated with fractures after this age. SUBJECTS AND METHODS: Cross-sectional study of 1284 women (mean +/- SD age, 73 +/- 4 years) who were 10 or more years' postmenopausal and who were recruited from electoral rolls in Auckland, New Zealand. Detailed information on their fracture, medical, menstrual, alcohol, and smoking histories was obtained using a standardized questionnaire. RESULTS: Nine percent of the women reported fractures before the age of 20 years; 7%, between the ages of 20 and 50 years; and 29%,after the age of 50 years. Fractures sustained between the ages of 20 and 50 years were associated with a 74% increase in the risk of fractures after the age of 50 years (odds ratio, 1.74; 95% confidence interval, 1.12-2.70), while fractures occurring before the age of 20 years were not (odds ratio, 1.01; confidence interval, 0.66 1.56). Multivariate analysis showed that after bone density, age, maternal history of hip fractures, age at menopause, weight, history of hormone replacement therapy, and smoking and alcohol histories were adjusted for, a history of fractures between the ages of 20 and 50 years remained a significant independent predictor of risk of fractures after the age of 50 years (risk ratio, 1.83; confidence interval, 1.12-2.76). CONCLUSIONS: Any fracture (unrelated to motor vehicle accidents) sustained between the ages of 20 and 50 years is associated with increased risk of fractures after the age of 50 years. Therefore, this is an important clinical risk factor that points to the need for bone density measurement, consideration of lifestyle modification, and antiosteoporosis therapies in these women. PMID- 11784218 TI - National patterns in the treatment of urinary tract infections in women by ambulatory care physicians. AB - BACKGROUND: Trimethoprim-sulfamethoxazole has consistently been the recommended drug for uncomplicated urinary tract infections in women. Which antibiotics physicians use has implications for patient outcomes, antimicrobial resistance, and costs. METHODS: This study was based on a sample survey of practicing physicians participating in the National Ambulatory Medical Care Survey from 1989 through 1998. Eligible visits were limited to those by women aged 18 to 75 years diagnosed with uncomplicated acute cystitis or urinary tract infection (N = 1478). We evaluated trends in the proportions of visits at which physicians prescribed (1) trimethoprim-sulfamethoxazole, (2) recommended fluoroquinolones, (3) nitrofurantoin, and (4) nonrecommended antibiotics (neither trimethoprim sulfamethoxazole nor recommended fluoroquinolones). We also identified predictors of specific antibiotic prescribing among visits to primary care physicians. RESULTS: The most frequently prescribed antibiotics were trimethoprim sulfamethoxazole, recommended fluoroquinolones, and nitrofurantoin. We found that the proportion of trimethoprim-sulfamethoxazole prescriptions declined from 48% in 1989-1990 to 24% in 1997-1998 (adjusted odds ratio [OR], 0.33; 95% confidence interval [CI], 0.21-0.52 per decade). Conversely, fluoroquinolone use increased (19% to 29%) (OR, 2.28; 95% CI, 1.35-3.83) as did nitrofurantoin prescribing (14% to 30%) (OR, 2.44; 95% CI, 1.44-4.13). Among primary care physicians, internists were the most likely to prescribe fluoroquinolones while obstetricians were the most likely to use nitrofurantoin. CONCLUSIONS: Ambulatory care physicians are increasing their use of fluoroquinolones and nitrofurantoin, even though they are not highly recommended and not the most cost-effective. Antibiotic prescribing in urinary tract infections may be influenced by clinical factors such as pregnancy and drug allergies but may also be shaped by nonclinical factors such as subspecialty culture. PMID- 11784219 TI - Supplemental oxygen use in ischemic stroke patients: does utilization correspond to need for oxygen therapy? AB - BACKGROUND: In 1994, the American Heart Association Stroke Council concluded that there were no data to support the routine use of supplemental oxygen in patients who had a stroke. More recently, supplemental oxygen has been suggested to be potentially detrimental. The purpose of this study was to determine the extent of oxygen use in ischemic stroke patients and whether patients receiving oxygen had indications for its use. METHODS: A literature search was performed to generate a comprehensive list of explicit criteria for supplemental oxygen use. When the literature disagreed, the criteria were included in the list to overestimate rather than underestimate the justification for oxygen use. A retrospective chart review of consecutive, nonintubated, ischemic stroke patients admitted to a university hospital was performed. Statistical tests and logistic regression models were constructed to identify the presence of unjustified oxygen use within the sample. Hospital charges were used to quantify opportunities for resource conservation. RESULTS: A total of 167 patient charts were reviewed yielding a total of 600 inpatient days abstracted. One hundred two patients (61.1%) received oxygen during some portion of their hospitalization. Of the 322 days that patients received oxygen, 147 (45.6%) met at least 1 criterion for oxygen use. Of the 278 days that patients did not receive oxygen, 69 (24.8%) met at least 1 of the criteria for oxygen use. There were 384 days for which no criteria were met. Of these, a patient still received oxygen 45.6% of the time (175 days). Factors associated with oxygen use included the presence of at least 1 justifying criteria as well as increasing age and male sex. Withholding oxygen from those not medically justified by the criteria could produce resource savings of roughly 45%. CONCLUSIONS: Using a literature-based list of criteria for supplemental oxygen use, only 45.6% of days of oxygen use were justified in our ischemic stroke population. This study demonstrates that oxygen therapy is commonly given to ischemic stroke patients without clear indication, and opportunities exist for substantial resource conservation. PMID- 11784220 TI - Borderline personality disorder in primary care. AB - BACKGROUND: Borderline personality disorder (BPD) is a severe and chronic psychiatric disorder characterized by marked impulsivity, instability of affect and interpersonal relationships, and suicidal behavior that can complicate medical care. Few data are available on its prevalence or clinical presentation outside of specialty mental health care settings. METHODS: We examined data from a survey conducted on a systematic sample (N = 218) from an urban primary care practice to study the prevalence, clinical features, comorbidity, associated impairment, and rate of treatment of BPD. Psychiatric assessments were conducted by mental health professionals using structured clinical interviews. RESULTS: Lifetime prevalence of BPD was 6.4% (14/218 patients). The BPD group had a high rate of current suicidal ideation (3 patients [21.4%]), bipolar disorder (3 [21.4%]), and major depressive (5 [35.7%]) and anxiety (8 [57.1%]) disorders. Half of the BPD patients reported not receiving mental health treatment in the past year and nearly as many (6 [42.9%]) were not recognized by their primary care physicians as having an ongoing emotional or mental health problem. CONCLUSIONS: The prevalence of BPD in primary care is high, about 4-fold higher than that found in general community studies. Despite availability of various pharmacological and psychological interventions that are helpful in treating symptoms of BPD, and despite the association of this disorder with suicidal ideation, comorbid psychiatric disorders, and functional impairment, BPD is largely unrecognized and untreated. These findings are also important for the primary care physician, because unrecognized BPD may underlie difficult patient physician relationships and complicate medical treatment. PMID- 11784221 TI - Forecasting the impact of a clinical practice guideline for perioperative beta blockers to reduce cardiovascular morbidity and mortality. AB - BACKGROUND: Beta-blockers reduce morbidity and mortality when administered to high-risk patients undergoing major noncardiac surgery, yet little is known about how often they are being prescribed. Clinical practice guidelines are tools that can be used to speed the translation of research into practice and may be one method to improve the use of beta-blockers. Before implementing any guideline, it is important to forecast its potential clinical and financial impact. METHODS: We conducted a retrospective cohort study, using administrative and medical record review data, of all adult patients undergoing major noncardiac surgery at Baystate Medical Center, Springfield, Mass, during a 1-month period in 1999. Patients with 2 or more cardiac risk factors or with documented coronary artery disease were classified as high risk and were considered eligible for treatment with a beta-blocker if they had no obvious contraindications to its use. We estimated the potential clinical benefit of treating eligible patients with a beta-blocker by extrapolating the treatment effect observed in a previously reported randomized clinical trial. RESULTS: Of 158 patients undergoing major noncardiac surgery, 67 (42.4%) seemed to be ideal candidates for treatment with perioperative beta-blockers. Of these 67 patients, 25 (37%) received a beta blocker at some time perioperatively. During the course of a year, we estimate that between 560 and 801 patients who do not receive beta-blockers might benefit from treatment with these medications. Full use of beta-blockers among eligible patients at our institution could result in 62 to 89 fewer deaths each year at an overall cost of $33 661 to $40 210. CONCLUSIONS: There seems to be a large opportunity to improve the quality of care of patients undergoing major noncardiac surgery by increasing the use of beta-blockers in the perioperative period. A clinical practice guideline may be one method to achieve these goals at little cost. PMID- 11784222 TI - Ethnicity and risk of diabetes-related lower extremity amputation: a population based, case-control study of African Caribbeans and Europeans in the United kingdom. AB - BACKGROUND: In the United States, people of black African descent with diabetes have 2 to 3 times the amputation risk of whites. This may be due to differences in care or pathophysiological characteristics. We therefore determined diabetes related amputation rates in African Caribbeans vs Europeans in the United Kingdom, where care delivery is more equitable. METHODS: We conducted an incidence and case-control study, based in London, England. All diabetes-related amputations performed between 1992 and 1997 were identified. Controls, those with diabetes but no amputation, were sampled from family practitioners. Risk factor data were abstracted from medical records. RESULTS: Incident diabetes-related amputation occurred in 67 Europeans and 19 African Caribbeans. Amputation rates, age standardized to the diabetic population, were 147 per 100 000 and 219 per 100 000 in African Caribbeans and Europeans, respectively (relative risk, 0.67; 95% confidence interval [CI], 0.32-1.40; P =.2). Case-control analyses were performed on 178 cases and 350 controls. The ethnic difference in amputation risk differed significantly by sex (P =.009 for interaction). The unadjusted odds ratio comparing African Caribbeans with Europeans in men was 0.31 (95% CI, 0.17-0.57; P<.001), and in women was 0.97 (95% CI, 0.49-1.85; P =.9). Adjustment for smoking attenuated the odds ratio in men to 0.45 (95% CI, 0.23-0.89, P =.02); adding neuropathy, peripheral vascular disease, and age attenuated the odds ratio further to 0.97 (95% CI, 0.34-2.73; P =.9). CONCLUSIONS: In contrast to the United States, we find no ethnic difference in diabetes-related amputation in women in the United Kingdom, but in men, amputation risk in African Caribbeans is one third that of Europeans. This was wholly accounted for by low smoking, neuropathy, and peripheral vascular disease rates. PMID- 11784223 TI - Elevated cardiac troponin levels in patients with submassive pulmonary embolism. AB - BACKGROUND: Cardiac troponins are reliable markers of myocardial injury that are being used increasingly in patients presenting with undifferentiated chest pain or dyspnea to diagnose an acute coronary syndrome. If elevated cardiac troponin levels also occur in patients with pulmonary embolism because of right ventricular dilation and myocardial injury, such patients could be misdiagnosed. We performed a prospective cohort study to determine the prevalence of elevated cardiac troponin I (cTnI) levels in patients with submassive pulmonary embolism. METHODS: Consecutive patients with objectively confirmed submassive pulmonary embolism and no previous history of ischemic heart disease, other cardiac disease, or renal insufficiency were included. Creatine kinase and cTnI levels were measured within 24 hours of clinical presentation on 2 occasions 8 to 12 hours apart. RESULTS: Of 24 patients with submassive pulmonary embolism, 5 (20.8%) had elevated cTnI levels of 0.4 microg/L or higher (95% confidence interval, 7.1-42.2%). One of these patients had a cTnI level higher than 2.3 microg/L that was suggestive of myocardial infarction. CONCLUSION: Pulmonary embolism should be considered in the differential diagnosis of patients presenting with undifferentiated chest pain or dyspnea and an elevated cardiac troponin level. PMID- 11784224 TI - Sex differences in risk factors for incident type 2 diabetes mellitus: the MONICA Augsburg cohort study. AB - OBJECTIVE: To examine sex-specific associations between cardiovascular risk factors, a parental history of diabetes, and type 2 diabetes mellitus (DM). METHODS: The study is based on 3052 men and 3114 women (aged 35 to 74 years) who participated in one of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995, who were free of DM at baseline and returned a follow-up questionnaire in 1998. Sex-specific hazard ratios (HRs) were estimated from Cox proportional hazard models. RESULTS: A total of 128 cases of incident DM among men and 85 cases among women were registered during the follow-up period. The age-standardized incidence rate was 5.8 per 1000 person-years for men and 4.0 per 1000 person-years for women. In multivariable survival analyses, age, body mass index, and a positive parental history of diabetes were important independent risk factors for DM in both sexes. High-density lipoprotein cholesterol level was inversely associated with DM in men and women. For other risk factors, sex-related differences were observed. Systolic blood pressure (HR per 10 mm Hg increase, 1.16), regular smoking (HR, 1.75), and high daily alcohol intake (HR, 1.95) predicted the development of DM in men only, whereas uric acid (HR per 1 mmol/L increase, 2.05) and physical inactivity during leisure time (HR, 1.80) were associated with diabetes development in women only. CONCLUSIONS: In men and women, most variables predicting future diabetes in the present study are also known to be important risk factors for cardiovascular disease and arteriosclerosis. However, there are sex-related dissimilarities that seem to be involved in disease development. PMID- 11784225 TI - Changing patient characteristics and the effect on mortality in endocarditis. AB - BACKGROUND: Limited data exist on recent demographic and microbiological changes in infective endocarditis (IE) and the impact of these changes on patient survival. METHODS: Data were collected from all patients with definite or possible IE at Duke University Medical Center, Durham, NC, from 1993 to 1999. Logistic regression analysis was used to identify demographic and microbiological changes that occurred in patients with IE over the study period. The impact of these changes on survival was evaluated using Cox proportional hazards modeling. RESULTS: Among the 329 study patients, rates of hemodialysis dependence, immunosuppression, and Staphylococcus aureus infection increased during the study period (P=.04, P=.008, and P<.001, respectively), while rates of infection due to viridans group streptococci decreased (P=.007). Hemodialysis was independently associated with S aureus infection (odds ratio, 3.1; 95% confidence interval, 1.6 5.9). Patients with S aureus IE had a higher 1-year mortality rate (43.9% vs 32.5%; P=.04) that persisted after adjustment for other illness severity characteristics (hazard ratio, 1.5; 95% confidence interval, 1.03-2.3). CONCLUSIONS: The demographic and microbiological characteristics of IE at our institution have changed over the past decade in ways that suggest a link between medical practice and IE characteristics. Staphylococcus aureus has emerged as a dominant cause of IE, and is an independent predictor of mortality. These findings identify clinical settings that may warrant closer surveillance and more aggressive measures in the identification and prevention of endocarditis. PMID- 11784226 TI - Ludovico Ariosto's angina. PMID- 11784227 TI - Gastrointestinal carcinoid tumor in a patient with chronic diarrhea. PMID- 11784228 TI - The intravenous use of oral acetylcysteine (mucomyst) for the treatment of acetaminophen overdose. PMID- 11784229 TI - Paradoxical reactions of tuberculosis in patients with the acquired immunodeficiency syndrome who are treated with highly active antiretroviral therapy. PMID- 11784230 TI - "Quality," nutrition, and pressure ulcers. PMID- 11784232 TI - Safety concerns about alosetron. PMID- 11784233 TI - Lotronex withdrawal. PMID- 11784234 TI - Risk of hip fracture in women: not only a smoking issue. PMID- 11784236 TI - Methylmalonic acid and clinical practice. PMID- 11784238 TI - Iodized salt and hypertension. PMID- 11784240 TI - Goal blood pressure in treating hypertension. PMID- 11784242 TI - Anticoagulation treatment in disabled patients. PMID- 11784244 TI - Prediction of cardiovascular mortality. PMID- 11784245 TI - The advantages of using non-HDL-C in the diagnosis and treatment of dyslipidemia. PMID- 11784247 TI - Surgery and functional outcomes in deaf children receiving cochlear implants before age 2 years. AB - OBJECTIVE: To examine the feasibility of cochlear implantation in children younger than 2 years regarding surgery and functional outcomes. DESIGN: Prospective study. SETTING: Tertiary pediatric cochlear implant center. PATIENTS: A consecutive sample of 12 children younger than 2 years at the time of cochlear implantation (8 boys and 4 girls). The cause of hearing loss was meningitis in 6 children and congenital in 6. INTERVENTIONS: Multichannel cochlear implantation using the Nucleus C124M (Cochlear Co, Sydney, Australia) device. Functional outcome was assessed using the Listening Progress Profile and the Categories of Auditory Performance. MAIN OUTCOME MEASURES: Perioperative and postoperative surgical complications and functional outcome. RESULTS: Eight children had a completely patent cochlea. Four children required a 3- to 5-mm drilling to reach the scala tympani because of ossification after meningitis. Full insertion was achieved in 11 patients; the other child received 18 electrodes. One patient had temporary facial nerve weakness; 2 others had wound edema and serous discharge that resolved with conservative management. In the longer term, 1 child experienced a single episode of acute otitis media; another had recurrent episodes of otitis media. Mean Listening Progress Profile scores increased from 1 to 42 and median Categories of Auditory Performance scores increased from 0 to 5 at 2 years postsurgery. Comparison with the scores in the 2- to 5-year group showed no significant differences. No significant tuning difficulties were experienced with all children. CONCLUSIONS: Cochlear implantation is feasible in children younger than 2 years without significant surgical complications or particular tuning difficulties. Functional results 2 years after implantation were as good as or better than those of children who underwent implantation between ages 2 and 5 years. PMID- 11784248 TI - Cytokine gene polymorphism in recurrent acute otitis media. AB - BACKGROUND: There is increasing evidence that a strong genetic component is involved in the predisposition to recurrent acute otitis media (rAOM). Cytokines play a key role in the pathogenesis of otitis media. Constitutional polymorphisms in cytokine genes may lead to individual variations in cytokine secretion. OBJECTIVE: To elucidate the role of cytokine gene polymorphisms in rAOM. SETTING: University hospital. PARTICIPANTS AND METHODS: Blood samples for genetic analysis were obtained from 63 individuals with rAOM from 20 different families and from 400 healthy blood donors. The medical history of the rAOM group was based on medical records and interview data. We studied the polymorphisms of tumor necrosis factor alpha, interleukin (IL) 1 alpha, IL-1 beta, and IL-1 receptor antagonist genes. RESULTS: The distribution of cytokine alleles in the rAOM group did not differ significantly from that of the control group. However, in patients with rAOM without a history of allergic disorders, allele frequencies of IL-1 alpha-889 differed significantly from those of controls (P =.03). CONCLUSIONS: There is no clear association between the polymorphism of studied cytokine genes and rAOM. However, the IL-1 alpha gene polymorphism may be associated with recurrent middle ear infections in a subgroup of patients without allergic disorders. PMID- 11784249 TI - Vibration-induced shift of the subjective visual horizontal: a sign of unilateral vestibular deficit. AB - BACKGROUND: Vibration to the head or neck excites vestibular and neck muscle spindle afferents. Can such vibrations improve the sensitivity of the subjective visual horizontal (SVH) test to chronic unilateral deficit of the vestibular system? DESIGN: Controlled experimental study. SETTING: Tertiary referral center. PATIENTS AND CONTROLS: Thirteen healthy subjects and 23 patients with chronic unilateral vestibular deficits after vestibular neurectomy or neurolabyrinthitis. Results of head-impulse test showed unilateral loss of function of all 3 semicircular canals in 14 patients and loss of anterior and lateral semicircular canals in 9 patients. INTERVENTION: Unilateral vibration (92 Hz; 0.6-mm amplitude) applied to sternocleidomastoid muscle (SCM) or mastoid bone. MAIN OUTCOME MEASURE: Results of SVH test (in degrees). RESULTS: Without vibration, 13 of 23 patients and all healthy subjects had SVH of less than 3 degrees (sensitivity, 43%; specificity, 100%). During vibration to the ipsilesional SCM, SVH increased to greater than 3 degrees in 21 of 23 patients but in only 1 of 13 healthy subjects (sensitivity, 91%; specificity, 92%). The patient group had significantly greater SVH shifts to the ipsilesional side than did healthy subjects in response to SCM and mastoid bone vibration on either side. The SVH shift during vibration to the ipsilesional SCM was significantly greater than that during vibration to the contralesional muscle (P<.001) or to the mastoid bone on either side (P<.05). The vibration-induced SVH shift was significantly greater in those patients with loss of 3 semicircular canals than in those with loss of 2 (P<.01). CONCLUSIONS: The sensitivity of the SVH test to chronic unilateral vestibular deficits can be improved by applying vibration to the SCM. The magnitude of vibratory SVH shift is related to the extent of unilateral deficit of the otolithic organs, vertical canals, or both. PMID- 11784250 TI - Maxillary removal and reinsertion in pediatric patients. AB - OBJECTIVE: To examine outcomes after the maxillary removal and reinsertion (MRR) approach for the treatment of anterior cranial base tumors in pediatric patients. DESIGN: Eligible patients were identified by medical record review. Consenting patients were studied via rhinoscopy, fiberoptic endoscopy, standard facial photographs, and cephalometric radiographs. SETTING: A tertiary care otolaryngology clinic. PATIENTS: Inclusion criteria were age younger than 16 years at time of initial procedure and a follow-up period of at least 6 months. Nine patients were eligible, and 5 enrolled. All were male patients (mean age, 13.8 years; age range, 11-15 years) treated for juvenile nasopharyngeal angiofibroma. MAIN OUTCOME MEASURES: History and examination were performed to evaluate occlusion, vision, facial growth, and tumor status. Cephalograms were used to calculate 3 standard cephalometric measurements: sella to A point, basion to A point, and condylion to A point. Cephalograms were examined for plate migration and bony resorption. RESULTS AND CONCLUSIONS: No major long-term complications were identified in the patients after MRR. Cephalometric analysis revealed minor abnormalities in 2 children, but no plate migration or bony resorption was identified in the removed and reinserted maxillae. No abnormal development patterns were detected on physical examination or when cephalometric measurements were compared with age- and race-matched normative data. Although further study is warranted, MRR seems safe and effective for treatment of pediatric patients with anterior cranial base tumors. PMID- 11784251 TI - Anesthetic techniques for pharyngeal flap surgery: effects on postoperative complications. AB - OBJECTIVE: To assess the effects of 2 different anesthetic techniques on early complications after superior pharyngeal flap surgery. DESIGN: Randomized, prospective, single-blind study. SETTING: Large referral hospital. PATIENTS: One hundred patients undergoing superior pharyngeal flap surgery for the correction of velopharyngeal insufficiency were randomly divided into 2 equal groups to receive either isoflurane or propofol-based anesthesia. INTERVENTIONS: Following induction of anesthesia with fentanyl citrate and propofol, patients were randomized to receive either isoflurane or propofol for the maintenance of general anesthesia. The inspired isoflurane concentration and propofol infusion rate were adjusted to maintain a stable depth of anesthesia as judged by clinical signs and hemodynamic responses to surgical stimuli. MAIN OUTCOME MEASURES: Recovery from anesthesia, recovery from surgery, and early postoperative complications. RESULTS: The groups were similar in age, weight, height, induction time, surgery time, extubation time, and anesthetic time. The time (mean +/- SD) required to achieve a maximal Steward Recovery Score was 7 +/- 14 minutes in the propofol group compared with 32 +/- 28 minutes in the isoflurane group (P<.04). No significant differences in postoperative patient satisfaction scores, time to first swallow, drinking time, and time to "home readiness" were noted. Overall, 17 patients (17%) developed airway-related complications and 2 of the patients (2%) were accounted as severe. Two patients (2%) bled from the operation site. However, there was no difference in the incidence of postoperative complications between the groups. CONCLUSIONS: When compared with isoflurane administration for maintenance of general anesthesia, propofol-based anesthesia was associated with more rapid mental and psychomotor recovery. However, airway-related complications and "home readiness" were similar between the groups. PMID- 11784252 TI - Micrometastatic tumor detection in patients with head and neck cancer: a preliminary report. AB - OBJECTIVE: To apply a new immunocytochemistry (ICC) assay to peripheral blood samples for micrometastatic circulating tumor cell detection in patients with head and neck squamous cell cancer (HNSCC). DESIGN: The ICC assay uses established monoclonal antibodies that bind to tumor-associated antigens combined with an enrichment system that uses positive selection with anti-human epithelial antigen (EpCAM antibody) to detect circulating tumor cells. SUBJECTS: Eighteen consecutive patients newly diagnosed as having HNSCC are described. RESULTS: Of the 18 patients, 8 (44%) demonstrated circulating tumor cells using the ICC assay. The numbers of patients positive for circulating tumor cells per stage are as follows: stage I, 1 of 1; stage II, 0 of 2; stage III, 2 of 5; stage IV, 5 of 6; and unknown stage, 0 of 4. The numbers of patients positive for circulating tumor cells per location are as follows: oral cavity, 1 of 2; oropharynx, 3 of 4; glottic area, 3 of 5; supraglottic area, 1 of 3; and unknown primary 0 of 4. CONCLUSIONS: Circulating tumor cells were identified in almost half of the patients using the ICC assay. In a literature review, we were not able to identify previous reports of circulating tumor cell detection in patients with HNSCC from peripheral blood samples using ICC or identify any study that has attempted to quantify circulating tumor cell levels. Although the clinical implications of circulating tumor cells in micrometastatic tumor detection in patients with HNSCC are still unknown, they may be significant. Long-term follow up may help elucidate the patients in whom conventional treatment may fail and, thus, those who may benefit from different treatment; it may also assist with the detection of recurrence with a simple blood collection. PMID- 11784253 TI - Development and validation of the neck dissection impairment index: a quality of life measure. AB - OBJECTIVES: To validate a health-related quality-of-life (QOL) instrument for patients following neck dissection and to identify the factors that affect QOL following neck dissection. DESIGN: Cross-sectional validation study. SETTING: The outpatient clinic of a tertiary care cancer center. PATIENTS: Convenience sample of 54 patients previously treated for head and neck cancer who underwent a selective neck dissection or modified radical neck dissection (64 total neck dissections). Patients had a minimum postoperative convalescence of 11 months. Thirty-two underwent accessory nerve-sparing modified radical neck dissection, and 32 underwent selective neck dissection. MAIN OUTCOME MEASURE: A 10-item, self report instrument, the Neck Dissection Impairment Index (NDII), was developed and validated. Reliability was evaluated with test-retest correlation and internal consistency using the Cronbach alpha coefficient. Convergent validity was assessed using the 36-Item Short-Form Health Survey (SF-36) and the Constant Shoulder Scale, a shoulder function test. Multiple variable regression was used to determine variables that most affected QOL following neck dissection RESULTS: The 10-item NDII test-retest correlation was 0.91 (P<.001) with an internal consistency Cronbach alpha coefficient of.95. The NDII correlated with the Constant Shoulder Scale (r = 0.85, P<.001) and with the SF-36 physical functioning (r = 0.50, P<.001) and role-physical functioning (r = 0.60, P<.001) domains. Using multiple variable regression, the variables that contributed most to QOL score were patient's age and weight, radiation treatment, and neck dissection type. CONCLUSIONS: The NDII is a valid, reliable instrument for assessing neck dissection impairment. Patient's age, weight, radiation treatment, and neck dissection type were important factors that affect QOL following neck dissection. PMID- 11784254 TI - Tracheoesophageal speech in a developing world community. AB - OBJECTIVES: To determine the tracheoesophageal speech results in a Third World medical practice; to examine the impact of socioeconomic status, literacy, and proximity to specialist services on tracheoesophageal speech; to assess whether these factors should affect patient selection for fistula speech; and to determine guidelines for voice prosthesis selection. DESIGN: Retrospective analysis. SETTING: Groote Schuur Hospital, Cape Town, South Africa, which serves a Third World community. PATIENTS: Ninety-seven consecutive patients who underwent total laryngectomy between January 1, 1996, and October 1, 1998. Patients who undergo total laryngectomy routinely have a primary tracheoesophageal fistula created for speech. MAIN OUTCOME MEASURES: Speech outcomes after total laryngectomy; tracheoesophageal speech in relation to social class, literacy, and proximity to specialist services; and experience with removable and indwelling valves. RESULTS: Fifty-nine (81%) of 73 patients acquired useful speech. Speech outcome was not affected by employment status or proximity to specialist services. Although speech was affected by literacy and housing, several illiterate shack dwellers acquired good speech. Average device life of removable prostheses was 16 weeks (>4 months in 35% [64/183]). Indwelling prostheses had an average life of 28 weeks. CONCLUSIONS: Tracheoesophageal speech results in a Third World community equate with those in the Developed World. All patients who undergo laryngectomy and have adequate manual dexterity and cognitive function should be given a trial of fistula speech. Removable voice prostheses can successfully be used as indwelling prostheses. PMID- 11784255 TI - Does laryngectomy improve swallowing after chemoradiotherapy? A case study. AB - Organ preservation protocols of high-dose chemoradiotherapy have become fairly common to treat head and neck cancers. However, significant swallowing problems can occur. This study examines swallowing, oral tongue pressures, and tongue base to-pharyngeal wall pressures in a patient who underwent total laryngectomy for improvement of swallowing after chemoradiotherapy for treatment of a hypopharyngeal tumor. The patient underwent concurrent videofluorographic and manometric examination of swallowing and examination of oral tongue pressures after the laryngectomy. One healthy subject was used as a control. After the laryngectomy, the patient no longer aspirated; however, he could swallow only liquids and pureed foods. He demonstrated difficulty with bolus clearance through the oral cavity and pharyngocervical esophagus. Pharyngeal pressures were reduced compared with those of the control subject. While total laryngectomy will stop unremitting aspiration, swallowing after chemoradiation may be severely compromised. This may not be overcome by total laryngectomy. PMID- 11784256 TI - Results of salvage treatment of the neck in patients with oral cancer. AB - BACKGROUND: About 50% of the patients with neck recurrences after the treatment of oral squamous cell carcinoma are not considered candidates for further treatment, and reported survival is generally poor. OBJECTIVE: To evaluate the prognostic importance of neck recurrences and results of salvage treatment in patients with oral carcinoma. PATIENTS: Five hundred thirteen patients with squamous cell carcinoma of the oral cavity underwent surgical treatment, with follow-up from less than 2 to 119 months (mean, 16.9 months). SETTING: Referral center, private or institutional practice, and ambulatory and hospital care center. INTERVENTION: Four hundred forty-eight patients underwent neck dissection, and 65, resection of the primary tumor only. Postoperative radiotherapy was used for 228. MAIN OUTCOME MEASURES: Rates of neck recurrences and survival after salvage treatment. RESULTS: Eighty-two patients (16.0%) had neck recurrences, including ipsilateral in 44, contralateral in 31, and bilateral in 7. Most neck recurrences (77 [94%]) were diagnosed within 2 years. Salvage treatment was attempted in 51 patients (62%). Of the patients with a previously untreated side of the neck, 27 underwent radical neck dissections (11 ipsilateral and 16 contralateral) and only 5 remained with no evidence of disease. The significant factors associated with survival after neck recurrence were type of previous neck dissection (P<.001), previous postoperative radiotherapy (P =.003), and interval free of neck recurrence (P<.001). CONCLUSIONS: Patients undergoing previous neck dissection and with recurrences diagnosed after 6 months are not usually candidates for curative salvage treatment and are at a high risk for death. Only 5 of 46 patients with recurrences in a previously untreated side of the neck survived after salvage treatment. Patients with neck recurrences have a poor prognosis, despite salvage treatment. PMID- 11784257 TI - Salvage surgery for recurrent nasopharyngeal carcinoma. AB - OBJECTIVE: To evaluate the results of salvage surgery for patients with primary recurrence of nasopharyngeal carcinoma after radiotherapy. DESIGN: Cohort study. SETTING: Academic tertiary referral center. PATIENTS: Eighteen consecutive patients with primary recurrence of nasopharyngeal carcinoma after radiation failure underwent nasopharyngectomy for cure via a facial translocation approach from July 1, 1993, to December 31, 1999. Follow-up ranged from 3 to 71 months. Five patients with skull base invasion required a combined neurosurgical approach to treatment. Seven patients had additional postoperative radiotherapy. RESULTS: The actuarial 3-year survival was 57%, while the local control was 78%. Four of 5 patients who had skull base invasion achieved local control. There was no surgical mortality, and the morbidity was 22%. CONCLUSION: Advances in skull base surgery make possible the effective control of primary recurrence of nasopharyngeal carcinoma, with acceptable mortality and morbidity. PMID- 11784258 TI - Neonatal dermoid cyst of the floor of the mouth extending to the midline neck. AB - We describe a male neonate who presented at birth with a compressible dermoid cyst that extended from the floor of the mouth to the midline of the neck. Ultrasonography revealed a fluid-filled sublingual mass. Magnetic resonance imaging performed when the patient was 1 week old demonstrated a 2-cm, cystic, left-sided, sublingual mass that crossed the midline without extension inferior to the mylohyoid muscle. At 3 months of age, the patient developed a 1-cm, solid, submental mass. At the time of surgery, the lesion had a fibromembranous tract that extended through the myolohyoid muscle to a 1-cm cyst in the submental region. Histologic sections depicted 2 dermoid cysts and a connecting fistula. This case represents the first report (to our knowledge) of a dermoid cyst presenting in a neonate as a mass in the floor of the mouth with extension to the midline of the neck. PMID- 11784259 TI - A case of ectopic parathyroid gland hyperplasia in the pyriform sinus. AB - Variability in the location of parathyroid glands is well recognized. There are usually 4 parathyroid glands located in the area of the thyroid gland, but embryologically, they may be found anywhere from the angle of the jaw to the pericardium. We report a case of an ectopic parathyroid gland in the pyriform sinus. It appeared as a tumorous lesion in the pyriform sinus owing to progress of secondary hyperparathyroidism. PMID- 11784260 TI - Pathology quiz case 1. Metastatic BCC and lymphoma. PMID- 11784261 TI - Pathology quiz case 2. Extramedullary hematopoeisis (EMH) of paranasal sinuses. PMID- 11784262 TI - Radiology quiz case 1. Temporally separated bilateral labrynthitis and sensorineural hearing loss. PMID- 11784263 TI - Radiology quiz case 2. Silent sinus syndrome: maxillary sinus atelectasis with enophthalmos. PMID- 11784264 TI - The evaluation of children with sensorineural hearing loss. PMID- 11784265 TI - Evaluation of childhood sensorineural hearing loss in the post-genome world. PMID- 11784266 TI - Use of laryngeal electromyography. PMID- 11784268 TI - Leech infestation as a potential cause of hemoptysis in childhood. PMID- 11784269 TI - Response to laser-assisted uvuloplasty for snoring. PMID- 11784271 TI - Staging system revision. PMID- 11784272 TI - Auditory function and the M34T allele of connexin 26. PMID- 11784274 TI - A comparison of five low back disability questionnaires: reliability and responsiveness. AB - BACKGROUND AND PURPOSE: The aim of this study was to examine 5 commonly used questionnaires for assessing disability in people with low back pain. The modified Oswestry Disability Questionnaire, the Quebec Back Pain Disability Scale, the Roland-Morris Disability Questionnaire, the Waddell Disability Index, and the physical health scales of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were compared in patients undergoing physical therapy for low back pain. SUBJECTS AND METHODS: Patients with low back pain completed the questionnaires during initial consultation with a physical therapist and again 6 weeks later (n=106). Test-retest reliability was examined for a group of 47 subjects who were classified as "unchanged" and a subgroup of 16 subjects who were self-rated as "about the same." Responsiveness was compared using standardized response means, receiver operating characteristic curves, and the proportions of subjects who changed by at least as much as the minimum detectable change (MDC) (90% confidence interval [CI] of the standard error for repeated measures). Scale width was judged as adequate if no more than 15% of the subjects had initial scores at the upper or lower end of the scale that were insufficient to allow change to be reliably detected. RESULTS: Intraclass correlation coefficients (2,1) calculated to measure reliability for the subjects who were classified as "unchanged" and those who were self-rated as "about the same" were greater than.80 for the Oswestry and Quebec questionnaires and the SF-36 Physical Functioning scale and less than.80 for the Waddell and Roland-Morris questionnaires and the SF-36 Role Limitations-Physical and Bodily Pain scales. None of the scales were more responsive than any other. DISCUSSION AND CONCLUSION: Measurements obtained with the modified Oswestry Disability Questionnaire, the SF-36 Physical Functioning scale, and the Quebec Back Pain Disability Scale were the most reliable and had sufficient width scale to reliably detect improvement or worsening in most subjects. The reliability of measurements obtained with the Waddell Disability Index was moderate, but the scale appeared to be insufficient to recommend it for clinical application. The Roland-Morris Disability Questionnaire and the Role Limitations-Physical and Bodily Pain scales of the SF-36 appeared to lack sufficient reliability and scale width for clinical application. PMID- 11784275 TI - Reliability of measurements obtained with the modified Ashworth scale in the lower extremities of people with stroke. AB - BACKGROUND AND PURPOSE: Abnormal muscle tone is a common motor disorder following stroke, which may require rehabilitation. The Modified Ashworth Scale is a 6 point rating scale that is used to measure muscle tone. The interrater and intrarater reliability of measurements obtained with the scale remain equivocal. The purpose of this study was to investigate the reliability of measurements obtained with the scale in the lower limb of patients with stroke. SUBJECTS: Twenty patients were tested 2 weeks after their stroke, and 12 patients were tested 12 weeks after their stroke. METHODS: Gastrocnemius, soleus, and quadriceps femoris muscles on the hemiplegic side were tested. RESULTS: Interrater reliability for 2 raters was poor, with a Kendall tau-b correlation for the combined muscle group of.062 (P=.461). For intrarater reliability, the Kendall tau-b correlation was.567 (P<.001). The agreement within one rater occurred mostly on the grade of 0. DISCUSSION AND CONCLUSION: The Modified Ashworth Scale yielded reliable measurements in the lower limb for a single examiner, and agreement was best on the grade of 0. The reliability between examiners was not good, which may bring into question the validity of measurements obtained with the scale. PMID- 11784276 TI - Effects of distally fixated versus nondistally fixated leg extensor resistance training on knee pain in the early period after anterior cruciate ligament reconstruction. AB - BACKGROUND AND PURPOSE: Nondistally fixated (ie, what is often referred to as "open kinetic chain" [OKC]) knee extensor resistance training appears to have lost favor for some forms of rehabilitation due partly to concerns that this exercise will irritate the extensor mechanism. In this randomized, single-blind clinical trial, nondistally fixated versus distally fixated (ie, often called "closed kinetic chain" [CKC]) leg extensor training were compared for their effects on knee pain. SUBJECTS: Forty-three patients recovering from anterior cruciate ligament (ACL) reconstruction surgery (34 male, 9 female; mean age=29 years, SD=7.9, range=16-54). METHODS: Knee pain was measured at 2 and 6 weeks after ACL reconstruction surgery using visual analog scales in a self-assessment questionnaire and during maximal isometric contractions of the knee extensors. Between test sessions, subjects trained 3 times per week using either OKC or CKC resistance of their knee and hip extensors as part of their physical therapy. RESULTS: No differences in knee pain were found between the treatment groups. DISCUSSION AND CONCLUSION: Open kinetic chain and CKC leg extensor training in the early period after ACL reconstruction surgery do not differ in their immediate effects on anterior knee pain. Based on these findings, further studies are needed using different exercise dosages and patient groups. PMID- 11784277 TI - Loads on an internal spinal fixation device during physical therapy. AB - BACKGROUND AND PURPOSE: Modified internal spinal fixation devices allow the measurement of the forces and moments acting on the implants. The aim of this study was to measure the loads on internal fixation devices for selected body positions and movements during physical therapy. SUBJECTS AND METHODS: Loads on an internal spinal fixation device were measured in 10 patients with degenerative instability or compression fractures using a telemeterized implant. RESULTS: Relatively low implant loads were found in the recumbent body positions. Most exercises performed in a lying position caused implant loads less than that measured for standing and are therefore not likely to increase the risk of screw breakage. Fixation device loads were lower for sitting relaxed than for standing. The highest implant loads (128% of the value for standing) were measured during walking. Standing up, sitting down, and lateral bending and axial rotation of the upper body while standing led to fixation device loads between 111% and 120% related to the value for standing. Even higher fixation device loads were measured for ventral flexion and extension of the upper body while standing. Kneeling on hands and knees, and flexing and extending the back in this position, caused implant loads that were lower than for standing. DISCUSSION AND CONCLUSION: Standing up, sitting down, and lateral bending and axial rotation of the upper body while standing may slightly increase the risk of pedicle screw breakage, whereas ventral flexion and extension of the upper body while standing may increase this risk considerably if the region bridged by the implant is distracted (the distance between upper and lower screws was increased) during surgery. However, walking is the exercise that plays the major role concerning pedicle screw breakage because it causes the highest bending moments of all exercises studied and it loads the fixation devices most frequently. PMID- 11784278 TI - Body weight support treadmill and overground ambulation training for two patients with chronic disability secondary to stroke. AB - BACKGROUND AND PURPOSE: Body weight support (BWS) treadmill training has recently been shown to be effective for gait training following stroke, but few researchers have measured the usefulness of this intervention in enhancing function, and there are no reports in which BWS overground ambulation was studied. The purposes of this case report were (1) to report the feasibility and patient tolerance for using a BWS system for overground ambulation, (2) to measure the function of patients with chronic stroke (2 years post-stroke) prior to and following BWS treadmill and overground ambulation training, and (3) to describe a protocol used for patient treatment progression using BWS treadmill training. CASE DESCRIPTIONS: The participants were 2 women, aged 87 and 93 years, who had strokes more than 2 years before data collection. A 10-m timed walk test, the Berg Balance Scale, the gait portion of the Tinetti Gait and Balance Assessment, and a measure of step length were administered. Intervention consisted of BWS ambulation training 3 times a week for 6 to 7 weeks. Each day there was BWS treadmill and overground training. OUTCOMES: Participant A improved most in 10-m walking time and Berg Balance Scale score. Participant B exhibited improvements in step length and 10-m walking time. DISCUSSION: The outcomes suggest that very old patients with chronic functional deficits secondary to cerebrovascular accident tolerated BWS treadmill and overground ambulation training and made improvements following this intervention. PMID- 11784280 TI - Central pattern generation of locomotion: a review of the evidence. AB - Neural networks in the spinal cord, referred to as "central pattern generators" (CPGs), are capable of producing rhythmic movements, such as swimming, walking, and hopping, even when isolated from the brain and sensory inputs. This article reviews the evidence for CPGs governing locomotion and addresses other factors, including supraspinal, sensory, and neuromodulatory influences, that interact with CPGs to shape the final motor output. Supraspinal inputs play a major role not only in initiating locomotion but also in adapting the locomotor pattern to environmental and motivational conditions. Sensory afferents involved in muscle and cutaneous reflexes have important regulatory functions in preserving balance and ensuring stable phase transitions in the locomotor cycle. Neuromodulators evoke changes in cellular and synaptic properties of CPG neurons, conferring flexibility to CPG circuits. Briefly addressed is the interaction of CPG networks to produce intersegmental coordination for locomotion. Evidence for CPGs in humans is reviewed, and although a comprehensive clinical review is not an objective, examples are provided of animal and human studies that apply knowledge of CPG mechanisms to improve locomotion. The final section deals with future directions in CPG research. PMID- 11784279 TI - Aging skeletal muscle: physiologic changes and the effects of training. PMID- 11784281 TI - A biologically plausible hypothesis. PMID- 11784282 TI - Mental practice. PMID- 11784283 TI - A systematic review of selected caries prevention and management methods. AB - A systematic review of the periodic scientific literature was undertaken to determine the strength of the evidence for the efficacy of professional caries preventive methods applied to high risk individuals, and the efficacy of professionally applied methods to arrest or reverse non-cavitated carious lesions. An initial search identified 1435 articles, of which 27 were eventually included in the review. Among the 22 studies addressing the prevention of carious lesions in caries-active or high risk individuals, the strength of the evidence was judged to be fair for fluoride varnishes and insufficient for all other methods. Among the seven studies addressing the management of non-cavitated carious lesions, the strength of the evidence for efficacy was judged to be insufficient for all methods. The results do not indicate that the preventive and management methods reviewed are not efficacious; rather, they demonstrate that not enough is known to determine the efficacy of the methods. Suggestions for strengthening the limited evidence base involve the following: i) increasing the number of studies that examine prevention among high risk individuals and non surgical management of non-cavitated lesions, ii) including a wider variety of subject ages, iii) targeting aspects of the efficacy questions not yet addressed, iv) strengthening research methods employed in the studies, and v) reporting methods and outcomes more completely. PMID- 11784284 TI - Is negative affectivity associated with oral quality of life? AB - OBJECTIVES: The personality trait of negative affectivity (NA) is associated with reports of worse physical health, more symptoms and worse health-related quality of life but its associations with oral quality of life (OQOL) are unexplored. In this study we examined the association of NA with OQOL. METHODS: We drew on data from two samples of older men: The VA Dental Longitudinal Study (DLS; n=177) and the Veterans Health Study (VHS; n=514), which included three measures of oral quality of life: the Oral Health-Related Quality of Life Measure (OHQOL), the Oral Health Impact Profile (OHIP), and the Geriatric Oral Health Assessment Instrument (GOHAI). For each OQOL measure, and the GOHAI and OHIP subscales, two regression models were estimated to examine the marginal change in variance due to NA: the first model included age, number of teeth, and self-rated oral health, and the second added NA. RESULTS: In both bivariate and multivariate analyses, higher NA was consistently associated with worse scores on the OQOL measures. In the regression analyses, NA explained an additional.01 to 18% of the variance in OQOL, explaining the most variance in the OHIP and the least in the OHQOL. The addition of NA explained more variance in the more subjective, psychologically oriented GOHAI and OHIP subscales than it did in the more objective, physical function oriented subscales. CONCLUSIONS: Psychosocial factors such as personality are significantly associated with quality of life ratings. Such associations should be taken into account when OQOL measurements are used and interpreted. PMID- 11784285 TI - Assessing risk indicators for dental caries in the primary dentition. AB - The aim of the present study was to assess indicators shown to be associated with the prevalence of caries in the primary dentition of 7-year-old Flemish schoolchildren. Cross-sectional first year data of the longitudinal Signal Tandmobiel survey were analysed (n=4468). Gender, age, oral hygiene habits, use of fluorides, dietary habits, geographical factors and parental modelling were the considered predictors. From the multiple logistic regression analysis, including schools as a random effect, and after adjusting for the confounding variables-educational system and province (stratification variables), gender and age-it became clear that the following risk indicators remained significant (at 5% level) for the presence of caries: frequency of toothbrushing (P=0.05) with an OR 1.24 for brushing less than once a day, age at start of brushing (P<0.001) with an OR=1.22 for a delay of 1 year, regular use of fluoride supplements (P<0.001) with an OR=1.54 for no use, daily use of sugar-containing drinks between meals (P<0.001) with an OR=1.38, and number of between-meals snacks (P=0.012) with an OR=1.22 for using more than 2 between-meal snacks. There was a significant difference (P<0.05) in caries experience determined by the geographical spread, with an explicit trend of caries declining from the east to the west. In a model with an ordinal response outcome, the daily use of sugar containing drinks between meals had a more pronounced effect when caries levels were high. From this study it became obvious that, in Flemish children, an early start of brushing and a brushing frequency of at least once a day need to be encouraged, while the use of sugar-containing drinks and snacks between meals needs to be restricted to a maximum of 2 per day. Geographical differences need to be investigated in more detail. PMID- 11784286 TI - A community trial of fluoridated powdered milk in Chile. AB - OBJECTIVE: To demonstrate the effectiveness of a dental caries prevention program on the primary dentition of Chilean rural children, using fluoridated powdered milk and milk derivatives. METHODS: Fluoridated milk and milk-cereal was given to about 1000 preschool children in Codegua, a rural community located in the 6th Region of Chile, using the standard National Complementary Feeding Program (PNAC). The daily fluoride dose from fluoridated powdered milk was estimated at 0.25 mg for infants (0-2 years old), 0.5 mg for children aged 2-3 years and 0.75 for children aged 3-6 years. Cross-sectional samples of children aged 3-6 years were taken from Codegua (study community) from 1994 to 1999 and from La Punta (control community) from 1997 and 1999. RESULTS: Significant reductions (72%) were observed in the dmfs indices in the 3-6-year-old groups in Codegua, when comparing 1999 with 1994 data. In 1999, children in the study community showed significantly lower dmfs than children in the control community (41%). The proportion of caries-free children in the study community increased after 4 years of program implementation (from 22.0% to 48.4%). CONCLUSION: Under Chilean rural conditions, fluoridation of powdered milk distributed through the PNAC is an effective caries prevention alternative for areas where water fluoridation might not be feasible. PMID- 11784287 TI - Efficacy of a dip slide test for mutans streptococci in caries risk assessment. AB - The aim of this study was to evaluate the efficacy of a dip slide test for mutans streptococci in caries risk assessment, when the microbiological results were compared to well-defined clinical criteria (DCC) for caries risk, clinically measured through high and low caries activity. Eighty-one volunteers from the 6th to 8th grades from public schools of Piracicaba, Sao Paulo, Brazil, were evaluated for dental caries. All free smooth surfaces were evaluated to check whether or not there were white spots. Based on the subjects' caries experience, a calibrated clinician divided them into groups of high and low caries activity. The subjects were submitted to a salivary test (CARITEST SM) from the same batch number. Kappa statistics (kappa) were applied to verify the reproducibility of the simplified test, checked through interexaminer agreement when the results were classified by independent and blind means. The microbiological results were validated according to expressions of sensitivity and specificity. A moderate agreement was verified as the results were classified according to 6 scores (kappa=0.55), and the agreement was substantial when the results were classified according to high and low microbiological count (kappa=0.78). The sensitivity and specificity values were 0.59 and 0.85, respectively, showing that the test was more specific than sensitive, and could thus better identify the low caries risk subjects. PMID- 11784288 TI - Contribution of changing diagnostic criteria toward reduction of caries between 1971 and 1997 in children attending the same school in Florianopolis, Brazil. AB - AIM: To assess the relative impact of changing diagnostic criteria on changes in the prevalence and severity of caries between 1971 and 1997. MATERIAL AND METHODS: All 12- and 13-year-old children attending the same school, "Padre Anchieta Primary School", in Brazil in 1971 (n=202) and 1997 (n=175) were examined by a single dentist. The criteria for the diagnosis of caries proposed by Radike in 1968 were used in both 1971 and 1997. In 1997, a second clinical examination was conducted and the WHO criteria proposed in 1987 were used. RESULTS: Comparison of caries experience expressed as changes in the mean DMFT scores indicated a 67.7% reduction between 1971 and 1997 from 9.2 to 3.0 when Radike's criteria were used in 1971 and the WHO criteria were used in 1997. The reduction in caries was independent of the diagnostic criteria adopted in the 1997 dental examination, but the reduction of caries was smaller, from 9.2 to 6.2 (31.8%), when caries experience in 1971 and 1997 was measured using Radike's criteria. CONCLUSION: The observed reduction of caries is not a statistical artifact. However, while 47.2% of this reduction is real, 52.8% of it is a statistical artifact due to changes in the criteria for measuring caries used by epidemiologists. PMID- 11784289 TI - Psychological disorders and dental anxiety in a young adult population. AB - OBJECTIVES: It has been suggested that some individuals who are fearful or anxious about dental treatment have a constitutional vulnerability to anxiety disorders as evidenced by the presence of multiple fears, generalized anxiety or panic disorders. This paper compares the prevalence of psychological disorders among dentally anxious and non-anxious groups drawn from the general population. METHODS: Data were obtained as part of a birth cohort study when study members were aged 18 years. They were assessed using the Dental Anxiety Scale (DAS) and the Diagnostic Interview Schedule (DIS). The disorders diagnosed by the DIS were major depressive episode, dysthymia, generalized anxiety disorder, panic disorder, agoraphobia, social phobia, simple phobia, obsessive compulsive disorder, conduct disorder, cannabis and alcohol dependence. RESULTS: Overall, 12.5% of study members had DAS scores of 13 or more and were considered to be dentally anxious. Those who were dentally anxious were more likely than the non anxious to be diagnosed with one or more psychological disorders (55.0% vs. 42.3%). However, those with DAS scores of 13 or 14 (moderately dentally anxious) were broadly similar to the non-anxious in terms of their psychological profile. This excess prevalence of psychological disorder was largely accounted for by high rates of disorder among those with DAS scores of 15 or more (highly dentally anxious). The highly anxious were more likely than the non-anxious to have a diagnosis of conduct disorder, agoraphobia, social phobia, simple phobia or alcohol dependence. Odds ratios ranged from 2.8 to 5.0 after controlling for the effects of gender. The data also suggested that dentally anxious individuals with psychological disorders were more likely to maintain their anxiety over time. CONCLUSIONS: In this population of young adults, high rates of psychological disorder were characteristic of those with high levels of dental anxiety. Psychological disorder was related to the maintenance of dental anxiety over time. PMID- 11784290 TI - Relationship between oral hygiene practices and oral status in dentate elderly people living in residential homes. AB - OBJECTIVES: To investigate the relationship between the oral hygiene practices of dentate elderly people living in residential homes, their requests for assistance and their oral health status. METHODS: 164 people (81.2+/-7.4 years) participated in an interview and oral examination, and provided a stimulated saliva sample. RESULTS: The mean number of coronal decayed surfaces (CDS) was 2.4+/-5.9, stimulated salivary levels (log(10)cfu/ml) of mutans streptococci, lactobacilli and yeasts were 1.6+/-2.1, 3.0+/-2.2, 2.1+/-1.7, respectively, and 53% had root decayed surfaces (RDS). Plaque (PI) and gingival (GI) Indices were 2.3+/-0.7 and 1.6+/-0.4 and denture debris scores (DDS) were high. 31% of the population cleaned their mouths twice daily without requesting help and they had significantly fewer yeasts, RDS, restorations on root surfaces, lower PI, GI (P<0.005) and DDS (P<0.0001) than the 69% who cleaned less often. 50% of those who cleaned less frequently requested assistance with oral hygiene but only 5% said that their carers supported them. Those residents who requested help had significantly higher levels of yeasts, lactobacilli (P<0.001), retained roots, DDS, RDS (P<0.005), PI and GI (P<0.0001). CONCLUSION: The elderly residents' perceived need for assistance with oral hygiene was related directly to oral hygiene status and to clinical indicators of mucosal and dental diseases. PMID- 11784292 TI - What does it mean to be natively unfolded? AB - Natively unfolded or intrinsically unstructured proteins constitute a unique group of the protein kingdom. The evolutionary persistence of such proteins represents strong evidence in the favor of their importance and raises intriguing questions about the role of protein disorders in biological processes. Additionally, natively unfolded proteins, with their lack of ordered structure, represent attractive targets for the biophysical studies of the unfolded polypeptide chain under physiological conditions in vitro. The goal of this study was to summarize the structural information on natively unfolded proteins in order to evaluate their major conformational characteristics. It appeared that natively unfolded proteins are characterized by low overall hydrophobicity and large net charge. They possess hydrodynamic properties typical of random coils in poor solvent, or premolten globule conformation. These proteins show a low level of ordered secondary structure and no tightly packed core. They are very flexible, but may adopt relatively rigid conformations in the presence of natural ligands. Finally, in comparison with the globular proteins, natively unfolded polypeptides possess 'turn out' responses to changes in the environment, as their structural complexities increase at high temperature or at extreme pH. PMID- 11784293 TI - A model for recognition of polychlorinated dibenzo-p-dioxins by the aryl hydrocarbon receptor. AB - Ligand binding by the aryl hydrocarbon receptor (AhR), a member of the bHLH-PAS family of transcriptional regulatory proteins, has been mapped to a region within the second 'PAS' domain, a conserved sequence motif first discovered in the Per ARNT-Sim family of proteins. In addition to the bacterial photoactive yellow protein (PYP), which had been proposed as a structural prototype for the three dimensional fold of PAS domains, two crystal structures of the PAS domain have recently been determined: the human potassium channel HERG and the heme binding domain of the bacterial O(2) sensing FixL protein. The three structures reveal a highly conserved structural framework in evolutionary rather distant PAS domains, provide a more general view of how these domains can recognize their ligands and suggest a structure-function relationship that we exploited to build a three dimensional model of the ligand binding domain (LBD) of the mouse aryl hydrocarbon receptor (mAhR). The model allowed us to putatively identify the residues responsible for the recognition of polychlorinated dibenzo-p-dioxins (PCDDs) by AhR receptors and to formulate an hypothesis on the signal transduction mechanism. PMID- 11784294 TI - Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo. AB - Mitochondrial uncoupling protein 1 (UCP1) is a specific marker of multilocular brown adipocytes. Ectopic UCP1 in white fat of aP2-Ucp1 mice mitigates development of obesity by both, increasing energy expenditure and decreasing in situ lipogenesis. In order to further analyse consequences of respiratory uncoupling in white fat, the effects of the ectopic UCP1 on the morphology of adipocytes and biogenesis of mitochondria in these cells were studied. In subcutaneous white fat of both aP2-Ucp1 and young control (5-week-old) mice, numerous multilocular adipocytes were found, while they were absent in adult (7- to 9-month-old) animals. Only unilocular cells were present in epididymal fat of both genotypes. In both fat depots of aP2-Ucp1 mice, the levels of the UCP1 transcript and UCP1 antigen declined during ageing, and they were higher in subcutaneous than in epididymal fat. Under no circumstances could ectopic UCP1 induce the conversion of unilocular into multilocular adipocytes. Presence of ectopic UCP1 in unilocular adipocytes was associated with the elevation of the transcripts for UCP2 and for subunit IV of mitochondrial cytochrome oxidase (COX IV), and increased content of mitochondrial cytochromes. Electron microscopy indicated changes of mitochondrial morphology and increased mitochondrial content due to ectopic UCP1 in unilocular adipocytes. In 3T3-L1 adipocytes, 2,4 dinitrophenol increased the levels of the transcripts for both COX IV and for nuclear respiratory factor-1. Our results indicate that respiratory uncoupling in unilocular adipocytes of white fat is capable of both inducing mitochondrial biogenesis and reducing development of obesity. PMID- 11784295 TI - Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T lymphocytes. AB - It has previously been shown that IFN-alpha is a potent inhibitor of IL-2 induced proliferation in primary T-lymphocytes, by selectively abrogating the downstream effects of IL-2 on the core cell cycle machinery regulating the G1/S transition. Theoretically this could be mediated through cross-talk between the signalling cascades activated by these cytokines, as several signalling components are known to be shared. IL-2 activates multiple signalling pathways that are important for T-cell proliferation and differentiation. In the present study, the effects of IFN-alpha on IL-2 signal transduction was investigated. The IFN-alpha induced inhibition of IL-2 induced proliferation in activated T-lymphocytes, was associated with a suppressed Jak3 protein expression as well as an inhibited prolonged Stat5 DNA binding, and a partially reduced expression of the Stat5 inducible gene IL-2R alpha. Our results provide a possible molecular link between the prominent antiproliferative effects of IFN-alpha on IL-2 induced T-cell proliferation and the signal transduction pathways emerging from the IL-2 receptor. PMID- 11784296 TI - A family of expressed antifreeze protein genes from the moth, Choristoneura fumiferana. AB - The freeze-intolerant insect, Choristoneura fumiferana (spruce budworm), produces multiple antifreeze protein (AFP) isoforms for protection during the overwintering stage. We now report the cloning of AFP genes from insects; Afp-Lu1 encodes a approximately 9-kDa AFP isoform, and Afp-Iu1 encodes a approximately 12 kDa AFP isoform. Both CfAFP genes have similar structures with a single 3- to 3.6 kb intron interrupting the coding region. The second exon of an additional CfAFP gene, 2.7a, encoding a new approximately 9-kDa isoform, was found 3.7 kb upstream of Afp-Lu1 and demonstrates that some AFP family members are linked in tandem. This gene appears to encode an AFP with 68-76% identity to previously isolated CfAFPs. With its eight Cys residues necessary for disulfide bonding and five perfectly conserved 'Thr button' (Thr-Xaa-Thr) ice-binding motifs, it can be modeled as a functional AFP. Southern blot analysis shows that there are approximately 17 genes in this AFP family, with each of the isoforms represented by two to five gene copies. Transcript accumulation from Afp-Lu1 and Afp-Iu1 (or closely related genes) was maximal during the overwintering stage, while 2.7a transcripts were only detected in first instars, larvae that are normally found only in the summer. Contrary to expectations, this differential expression demonstrates that CfAFP gene family transcripts are primarily regulated during development, rather than by seasonally low temperatures. PMID- 11784297 TI - Characterization of a partially folded intermediate of stem bromelain at low pH. AB - Equilibrium studies on the acid included denaturation of stem bromelain (EC 3.4.22.32) were performed by CD spectroscopy, fluorescence emission spectroscopy and binding of the hydrophobic dye, 1-anilino 8-naphthalene sulfonic acid (ANS). At pH 2.0, stem bromelain lacks a well defined tertiary structure as seen by fluorescence and near-UV CD spectra. Far-UV CD spectra show retention of some native like secondary structure at pH 2.0. The mean residue ellipticities at 208 nm plotted against pH showed a transition around pH 4.5 with loss of secondary structure leading to the formation of an acid-unfolded state. With further decrease in pH, this unfolded state regains most of its secondary structure. At pH 2.0, stem bromelain exists as a partially folded intermediate containing about 42.2% of the native state secondary structure Enhanced binding of ANS was observed in this state compared to the native folded state at neutral pH or completely unfolded state in the presence of 6 m GdnHCl indicating the exposure of hydrophobic regions on the protein molecule. Acrylamide quenching of the intrinsic tryptophan residues in the protein molecule showed that at pH 2.0 the protein is in an unfolded conformation with more tryptophan residues exposed to the solvent as compared to the native conformation at neutral pH. Interestingly, stem bromelain at pH 0.8 exhibits some characteristics of a molten globule, such as an enhanced ability to bind the fluorescent probe as well as considerable retention of secondary structure. All the above data taken together suggest the existence of a partially folded intermediate state under low pH conditions. PMID- 11784298 TI - The presence of phosphate at a catalytic site suppresses the formation of the MgADP-inhibited form of F(1)-ATPase. AB - F1-ATPase is inactivated by entrapment of MgADP in catalytic sites and reactivated by MgATP or P(i). Here, using a mutant alpha(3)beta(3)gamma complex of thermophilic F(1)-ATPase (alpha W463F/beta Y341W) and monitoring nucleotide binding by fluorescence quenching of an introduced tryptophan, we found that P(i) interfered with the binding of MgATP to F(1)-ATPase, but binding of MgADP was interfered with to a lesser extent. Hydrolysis of MgATP by F(1)-ATPase during the experiments did not obscure the interpretation because another mutant, which was able to bind nucleotide but not hydrolyse ATP (alpha W463F/beta E190Q/beta Y341W), also gave the same results. The half-maximal concentrations of P(i) that suppressed the MgADP-inhibited form and interfered with MgATP binding were both approximately 20 mm. It is likely that the presence of P(i) at a catalytic site shifts the equilibrium from the MgADP-inhibited form to the enzyme-MgADP-P(i) complex, an active intermediate in the catalytic cycle. PMID- 11784299 TI - Engineering and use of (32)P-labeled human recombinant interleukin-11 for receptor binding studies. AB - Human interleukin-11 (hIL-11) is a pleiotropic cytokine that is involved in numerous biological activities such as hematopoiesis, osteoclastogenesis, neurogenesis and female fertility. IL-11 is obviously a key reagent to study the IL-11 receptors. However, conventional radio-iodination techniques lead to a loss of IL-11 bioactivity. Here, we report the construction and the production of a new recombinant human IL-11 (FP Delta IL-11). In this molecule, a specific phosphorylation site (RRASVA) has been introduced at the N-terminus of rhIL-11. It can be specifically phosphorylated by bovine heart protein kinase and accordingly, easily radiolabeled with (32)P. A high radiological specific activity (250,000 c.p.m x ng(-1) of protein) was obtained with the retention of full biological activity of the protein. The binding of (32)P-labeled FP Delta IL 11 to Ba/F3 cells stably transfected with plasmids encoding human IL-11 receptors alpha and beta chains (IL-11R alpha and gp130) was specific and saturable with a high affinity as determined from Scatchard plot analysis. Availability of this new ligand should prompt further studies on IL-11R structure, expression and regulation. PMID- 11784300 TI - Conditionally immortalized adrenocortical cell lines at undifferentiated states exhibit inducible expression of glucocorticoid-synthesizing genes. AB - To facilitate studies on differentiation of adrenocortical cells and regulation of steroidogenic genes, we established cell lines from adrenals of adult transgenic mice harboring a temperature-sensitive large T-antigen gene of simian virus 40. Adrenal glands of the mice exhibited normal cortical zonation including a functionally undifferentiated cell-layer between the aldosterone-synthesizing zona glomerulosa cells and the corticosterone-synthesizing zona fasciculata cells. At a permissive temperature (33 degrees C), established cell lines AcA201, AcE60 and AcA101 expressed steroidogenic genes encoding steroidogenic factor-1, cholesterol side-chain cleavage P450scc, and steroidogenic acute regulatory protein, which are expressed throughout adrenal cortices and gonads. Genes encoding 3 beta-hydroxysteroid dehydrogenase and steroid 21-hydroxylase P450c21, which catalyze the intermediate steps for syntheses of both aldosterone and corticosterone, were inducible in the three cell lines in temperature- and/or dibutyryl cAMP-dependent manners. Notably, these cell lines displayed distinct expression patterns of the steroid 11 beta-hydroxylase P45011 beta gene responsible for the zone-specific synthesis of corticosterone. AcA201 cells expressed the P45011 beta gene at 33 degrees C, showing the property of the zona fasciculata cells, while AcE60 cells expressed it upon a shift to a nonpermissive temperature (39 degrees C). On the other hand, AcA101 expressed the P45011 beta gene at 39 degrees C synergistically with exposure to dibutyryl cAMP. None of these clones express the zona glomerulosa-specific aldosterone synthase P450aldo gene under the conditions we tested. These results show that AcE60 and AcA101 cells display a pattern of the steroidogenic gene expression similar to that of the undifferentiated cell-layer and are capable of differentiating into the zona fasciculata-like cells in vitro. PMID- 11784301 TI - Purification and characterization of the human adenosine A(2a) receptor functionally expressed in Escherichia coli. AB - The adenosine A(2a) receptor belongs to the seven transmembrane helix G-protein coupled receptor family, is abundant in striatum, vasculature and platelets and is involved in several physiological processes such as blood pressure regulation and protection of cells during anoxia. For structural and biophysical studies we have expressed the human adenosine A(2a) receptor (hA2aR) at high levels inserted into the Escherichia coli inner membrane, and established a purification scheme. Expression was in fusion with the periplasmic maltose-binding protein to levels of 10-20 nmol of receptor per L of culture, as detected with the specific antagonist ligand [(3)H]ZM241385. As the receptor C-terminus was proteolyzed upon solubilization, a protease-resistant but still functional receptor was created by truncation to Ala316. Addition of the sterol, cholesteryl hemisuccinate, allowed a stable preparation of functional hA2aR solubilized in dodecylmaltoside to be obtained, and, increased the stability of the receptor solubilized in other alkylmaltosides. Purification to homogeneity was achieved in three steps, including ligand affinity chromatography based on the antagonist xanthine amine congener. The purified hA2aR fusion protein bound [(3)H]ZM241385 with a K(d) of 0.19 nm and an average B(max) of 13.7 nmol x mg(-1) that suggests 100% functionality. Agonist affinities for the purified solubilized receptor were higher than those for the membrane-bound form. Sufficient pure, functional hA2aR can now be prepared regularly for structural studies. PMID- 11784302 TI - Structures of two O-chain polysaccharides of Citrobacter gillenii O9a,9b lipopolysaccharide. A new homopolymer of 4-amino-4,6-dideoxy-D-mannose (perosamine). AB - Mild acid degradation of the lipopolysaccharide of Citro- bacter gillenii O9a,9b released a polysaccharide (PS), which was found to consist of a single monosaccharide, 4- acetamido-4,6-dideoxy-d-mannose (d-Rha4NAc, N-acetyl-d perosamine). PS was studied by methylation analysis and (1)H-NMR and (13)C-NMR spectroscopy, using two-dimensional (1)H,(1)H COSY, TOCSY, NOESY, and H-detected (1)H,(13)C heteronuclear correlation experiments. It was found that PS includes two structurally different polysaccharides: an alpha1-->2-linked homopolymer of N acetyl-d-perosamine [-->2)-alpha-d-Rhap4NAc-(1-->, PS2] and a polysaccharide composed of tetrasaccharide repeating units (PS1) with the following structure: - >3)-alpha-d-Rhap4NAc-(1-->2)-alpha-d-Rhap4NAc-(1-->2)-alpha-d-Rhap4NAc-(1-->3) alpha-d-Rhap4 N Ac2Ac-(1--> where the degree of O-acetylation of a 3-substituted Rha4NAc residue at position 2 is approximately 70%. PS could be fractionated into PS1 and PS2 by gel-permeation chromatography on TSK HW-50S. Matrix-assisted laser desorption ionization MS data indicate sequential chain elongation of both PS1 and PS2 by a single sugar unit, with O-acetylation in PS1 beginning at a certain chain length. Anti-(C. gillenii O9a,9b) serum reacted with PS1 in double immunodiffusion and immunoblotting, whereas neither PS2 nor the lipopolysaccharide of Vibrio cholerae O1 with a structurally related O-chain polysaccharide were reactive. PMID- 11784303 TI - Amphibian peptides that inhibit neuronal nitric oxide synthase. Isolation of lesuerin from the skin secretion of the Australian Stony Creek frog Litoria lesueuri. AB - Two neuropeptides have been isolated and identified from the secretions of the skin glands of the Stony Creek Frog Litoria lesueuri. The first of these, the known neuropeptide caerulein 1.1, is a common constituent of anuran skin secretions, and has the sequence pEQY(SO3)TGWMDF-NH2. This neuropeptide is smooth muscle active, an analgaesic more potent than morphine and is also thought to be a hormone. The second neuropeptide, a new peptide, has been named lesueurin and has the primary structure GLLDILKKVGKVA-NH2. Lesueurin shows no significant antibiotic or anticancer activity, but inhibits the formation of the ubiquitous chemical messenger nitric oxide from neuronal nitric oxide synthase (nNOS) at IC(50) (16.2 microm), and is the first amphibian peptide reported to show inhibition of nNOS. As a consequence of this activity, we have tested other peptides previously isolated from Australian amphibians for nNOS inhibition. There are three groups of peptides that inhibit nNOS (IC(50) at microm concentrations): these are (a) the citropin/aurein type peptides (of which lesueurin is a member), e.g. citropin 1.1 (GLFDVIKKVASVIGGL-NH(2)) (8.2 microm); (b) the frenatin type peptides, e.g. frenatin 3 (GLMSVLGHAVGNVLG GLFKPK-OH) (6.8 microm); and (c) the caerin 1 peptides, e.g. caerin 1.8 (GLFGVLGSIAKHLLPHVVPVIAEKL-NH(2)) (1.7 microm). From Lineweaver-Burk plots, the mechanism of inhibition is revealed as noncompetitive with respect to the nNOS substrate arginine. When the nNOS inhibition tests with the three peptides outlined above were carried out in the presence of increasing concentrations of Ca(2+) calmodulin, the inhibition dropped by approximately 50% in each case. In addition, these peptides also inhibit the activity of calcineurin, another enzyme that requires the presence of the regulatory protein Ca(2+) calmodulin. It is proposed that the amphibian peptides inhibit nNOS by interacting with Ca(2+)calmodulin, and as a consequence, blocks the attachment of this protein to the calmodulin domain of nNOS. PMID- 11784304 TI - High pressure-induced changes of biological membrane. Study on the membrane-bound Na(+)/K(+)-ATPase as a model system. AB - In order to study the pressure-induced changes of biological membrane, hydrostatic pressures of from 0.1 to 400 MPa were applied to membrane-bound Na(+)/K(+)-ATPase from pig kidney as a model system of protein and lipid membrane. The activity showed at least a three-step change induced by pressures of 0.1-100 MPa, 100-220 MPa, and 220 MPa or higher. At pressures of 100 MPa or lower a decrease in the fluidity of lipid bilayer and a reversible conformational change in transmembrane protein is induced, leading to the functional disorder of membrane-associated ATPase activity. A pressure of 100-220 MPa causes a reversible phase transition in parts of the lipid bilayer from the liquid crystalline to the gel phase and the dissociation of and/or conformational changes in the protein subunits. These changes could cause a separation of the interface between alpha and beta subunits and between protein and the lipid bilayer to create transmembrane tunnels at the interface. Tunnels would be filled with water from the aqueous environment and take up tritiated water. A pressure of 220 MPa or higher irreversibly destroys and fragments the gross membrane structure, due to protein unfolding and interface separation, which is amplified by the increased pressure. These findings provide an explanation for the high pressure-induced membrane-damage to subcellular organelles. PMID- 11784305 TI - Expression of glucose transporter-2, glucokinase and mitochondrial glycerolphosphate dehydrogenase in pancreatic islets during rat ontogenesis. AB - To gain better insight into the insulin secretory activity of fetal beta cells in response to glucose, the expression of glucose transporter 2 (GLUT-2), glucokinase and mitochondrial glycerol phosphate dehydrogenase (mGDH) were studied. Expression of GLUT-2 mRNA and protein in pancreatic islets and liver was significantly lower in fetal and suckling rats than in adult rats. The glucokinase content of fetal islets was significantly higher than of suckling and adult rats, and in liver the enzyme appeared for the first time on about day 20 of extrauterine life. The highest content of hexokinase I was found in fetal islets, after which it decreased progressively to the adult values. Glucokinase mRNA was abundantly expressed in the islets of all the experimental groups, whereas in liver it was only present in adults and 20-day-old suckling rats. In fetal islets, GLUT-2 and glucokinase protein and their mRNA increased as a function of increasing glucose concentration, whereas reduced mitochondrial citrate synthase, succinate dehydrogenase and cytochrome c oxidase activities and mGDH expression were observed. These findings, together with those reported by others, may help to explain the decreased insulin secretory activity of fetal beta cells in response to glucose. PMID- 11784306 TI - Human and Drosophila UDP-galactose transporters transport UDP-N acetylgalactosamine in addition to UDP-galactose. AB - A putative Drosophila nucleotide sugar transporter was characterized and shown to be the Drosophila homologue of the human UDP-Gal transporter (hUGT). When the Drosophila melanogaster UDP-Gal transporter (DmUGT) was expressed in mammalian cells, the transporter protein was localized in the Golgi membranes and complemented the UDP-Gal transport deficiency of Lec8 cells but not the CMP-Sia transport deficiency of Lec2 cells. DmUGT and hUGT were expressed in Saccharomyces cerevisiae cells in functionally active forms. Using microsomal vesicles isolated from Saccharomyces cerevisiae expressing these transporters, we unexpectedly found that both hUGT and DmUGT could transport UDP-GalNAc as well as UDP-Gal. When amino-acid residues that are conserved among human, murine, fission yeast and Drosophila UGTs, but are distinct from corresponding ones conserved among CMP-Sia transporters (CSTs), were substituted by those found in CST, the mutant transporters were still active in transporting UDP-Gal. One of these mutants in which Asn47 was substituted by Ala showed aberrant intracellular distribution with concomitant destabilization of the protein product. However, this mutation was suppressed by an Ile51 to Thr second-site mutation. Both residues were localized within the first transmembrane helix, suggesting that the structure of the helix contributes to the stabilization and substrate recognition of the UGT molecule. PMID- 11784307 TI - DAP kinase activity is critical for C(2)-ceramide-induced apoptosis in PC12 cells. AB - Exposure of PC12 cells to C(2)-ceramide results in dose- dependent apoptosis. Here, we investigate the involvement of death-associated protein (DAP) kinase, initially identified as a positive mediator of the interferon-gamma-induced apoptosis of HeLa cells, in the C(2)-ceramide-induced apoptosis of PC12 cells. DAP kinase is endogenously expressed in these cells. On exposure of PC12 cells to 30 microm C(2)-ceramide, both the total (assayed in the presence of Ca(2+)/calmodulin) and Ca(2+)/calmodulin-independent (assayed in the presence of EGTA) DAP kinase activities were transiently increased 5.0- and 12.2-fold, respectively, at 10 min, and then decreased to 1.7- and 3.4-fold at 90 min. After 10 min exposure to 30 microm C(2)-ceramide, the Ca(2+)/calmodulin independent activity/ total activity ratio increased from 0.22 to 0.60. These effects were dependent on the C(2)-ceramide concentration. C(8)-ceramide, another active ceramide analog, also induced apoptosis and activated DAP kinase, while C(2) dihydroceramide, an inactive ceramide analog, failed to induce apoptosis and increase DAP kinase activity. Furthermore, transfection studies revealed that overexpression of wild-type DAP kinase enhanced the sensitivity to C(2)- and C(8) ceramide, while a catalytically inactive DAP kinase mutant and a construct containing the death domain and C-terminal tail of DAP kinase, which act in a dominant-negative manner, rescued cells from C(2)-, and C(8)-ceramide-induced apoptosis. These findings demonstrate that DAP kinase is an important component of the apoptotic machinery involved in ceramide-induced apoptosis, and that the intrinsic DAP kinase activity is critical for ceramide-induced apoptosis. PMID- 11784308 TI - A Raman optical activity study of rheomorphism in caseins, synucleins and tau. New insight into the structure and behaviour of natively unfolded proteins. AB - The casein milk proteins and the brain proteins alpha-synuclein and tau have been described as natively unfolded with random coil structures, which, in the case of alpha-synuclein and tau, have a propensity to form the fibrils found in a number of neurodegenerative diseases. New insight into the structures of these proteins has been provided by a Raman optical activity study, supplemented with differential scanning calorimetry, of bovine beta- and kappa-casein, recombinant human alpha-, beta- and gamma-synuclein, together with the A30P and A53T mutants of alpha-synuclein associated with familial cases of Parkinson's disease, and recombinant human tau 46 together with the tau 46 P301L mutant associated with inherited frontotemporal dementia. The Raman optical activity spectra of all these proteins are very similar, being dominated by a strong positive band centred at approximately 1318 cm(-1) that may be due to the poly(l-proline) II (PPII) helical conformation. There are no Raman optical activity bands characteristic of extended secondary structure, although some unassociated beta strand may be present. Differential scanning calorimetry revealed no thermal transitions for these proteins in the range 15-110 degrees C, suggesting that the structures are loose and noncooperative. As it is extended, flexible, lacks intrachain hydrogen bonds and is hydrated in aqueous solution, PPII helix may impart a rheomorphic (flowing shape) character to the structure of these proteins that could be essential for their native function but which may, in the case of alpha-synuclein and tau, result in a propensity for pathological fibril formation due to particular residue properties. PMID- 11784309 TI - Cold adaptation of xylose isomerase from Thermus thermophilus through random PCR mutagenesis. Gene cloning and protein characterization. AB - Random PCR mutagenesis was applied to the Thermus thermophilus xylA gene encoding xylose isomerase. Three cold-adapted mutants were isolated with the following amino-acid substitutions: E372G, V379A (M-1021), E372G, F163L (M-1024) and E372G (M-1026). The wild-type and mutated xylA genes were cloned and expressed in Escherichia coli HB101 using the vector pGEM-T Easy, and their physicochemical and catalytic properties were determined. The optimum pH for xylose isomerization activity for the mutants was approximately 7.0, which is similar to the wild-type enzyme. Compared with the wild-type, the mutants were active over a broader pH range. The mutants exhibited up to nine times higher catalytic rate constants (k(cat)) for d-xylose compared with the wild-type enzyme at 60 degrees C, but they did not show any increase in catalytic efficiency (k(cat)/K(m)). For d glucose, both the k(cat) and the k(cat)/K(m) values for the mutants were increased compared with the wild-type enzyme. Furthermore, the mutant enzymes exhibited up to 255 times higher inhibition constants (K(i)) for xylitol than the wild-type, indicating that they are less inhibited by xylitol. The thermal stability of the mutated enzymes was poorer than that of the wild-type enzyme. The results are discussed in terms of increased molecular flexibility of the mutant enzymes at low temperatures. PMID- 11784310 TI - Proliferating cell nuclear antigen from a basidiomycete, Coprinus cinereus. Alternative truncation and expression in meiosis. AB - The primary purpose of the present study was to investigate whether DNA replication at meiotic prophase also requires replication factors, especially proliferating cell nuclear antigen (PCNA). We cloned PCNA cDNAs (CoPCNA) from a cDNA library made from basidia of the basidiomycete, Coprinus cinereus. Interestingly, although CoPCNA is a single-copy gene in the genome, two different PCNA cDNA species were isolated using degenerate primers and a meiotic cDNA library, and were designated as CoPCNA-alpha and CoPCNA-beta. CoPCNA-beta was made by truncating at specific sites in CoPCNA-alpha mRNA, 5'-AAGAAGGAGAAG-3' and 5'-GAAGAGGAAGAA-3'. Both of these sequences were present in exon IV in the genomic sequence, and interestingly the former was the same as the inverse sequence of the latter. CoPCNA-alpha was 107 amino acids larger than human PCNA, and so the 107 amino-acid sequence was inserted in a loop, the so-called D2E2 loop, in human PCNA. Northern blotting analysis indicated that CoPCNA was expressed not only at premeiotic S but also at the meiotic prophase stages such as leptotene and early zygotene, just before and when karyogamy occurs and the homologous chromosomes pair. Western blotting analysis using anti-(CoPCNA-alpha) Ig revealed that at least two CoPCNA mRNAs before and after truncation were translated at the meiotic prophase as CoPCNA-alpha and CoPCNA-beta. PMID- 11784311 TI - Inhibition of nuclear pre-mRNA splicing by antibiotics in vitro. AB - A number of antibiotics have been reported to disturb the decoding process in prokaryotic translation and to inhibit the function of various natural ribozymes. We investigated the effect of several antibiotics on in vitro splicing of a eukaryotic nuclear pre-mRNA (beta-globin). Of the eight antibiotics studied, erythromycin, Cl-tetracycline and streptomycin were identified as splicing inhibitors in nuclear HeLa cell extract. The K(i) values were 160, 180 and 230 microm, respectively. Cl-tetracycline-mediated and streptomycin-mediated splicing inhibition were in the molar inhibition range for hammerhead and human hepatitis delta virus ribozyme self-cleavage (tetracycline), of group-I intron self splicing (streptomycin) and inhibition of RNase P cleavage by some aminoglycosides. Cl-tetracycline and the aminocyclitol glycoside streptomycin were found to have an indirect effect on splicing by unspecific binding to the pre-mRNA, suggesting that the inhibition is the result of disturbance of the correct folding of the pre-mRNA into the splicing-compatible tertiary structure by the charged groups of these antibiotics. The macrolide, erythromycin, the strongest inhibitor, had only a slight effect on formation of the presplicing complexes A and B, but almost completely inhibited formation of the splicing active C complex by binding to nuclear extract component(s). This results in direct inhibition of the second step of pre-mRNA splicing. To our knowledge, this is the first report on specific inhibition of nuclear splicing by an antibiotic. The functional groups involved in the interaction of erythromycin with snRNAs and/or splicing factors require further investigation. PMID- 11784313 TI - A catalytically inactive beta 1,4-N-acetylglucosaminyltransferase III (GnT-III) behaves as a dominant negative GnT-III inhibitor. AB - beta 1,4-N-Acetylglucosaminyltransferase III (GnT-III) plays a regulatory role in the biosynthesis of N-glycans, and it has been suggested that its product, a bisecting GlcNAc, is involved in a variety of biological events as well as in regulating the biosynthesis of the oligosaccharides. In this study, it was found, on the basis of sequence homology, that GnT-III contains a small region that is significantly homologous to both snail beta 1,4GlcNAc transferase and beta1,4Gal transferase-1. Subsequent mutational analysis demonstrated an absolute requirement for two conserved Asp residues (Asp321 and Asp323), which are located in the most homologous region of rat GnT-III, for enzymatic activity. The overexpression of Asp323-substituted, catalytically inactive GnT-III in Huh6 cells led to the suppression of the activity of endogenous GnT-III, but no significant decrease in its expression, and led to a specific inhibition of the formation of bisected sugar chains, as shown by structural analysis of the total N-glycans from the cells. These findings indicate that the mutant serves a dominant negative effect on a specific step in N-glycan biosynthesis. This type of 'dominant negative glycosyltransferase', identified has potential value as a powerful tool for defining the precise biological roles of the bisecting GlcNAc structure. PMID- 11784312 TI - Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin. AB - The serpin plasminogen activator inhibitor type 1 (PAI-1) plays an important role in physiological processes such as thrombolysis and fibrinolysis, as well as pathophysiological processes such as thrombosis, tumor invasion and metastasis. In addition to inhibiting serine proteases, mainly tissue-type (tPA) and urokinase-type (uPA) plasminogen activators, PAI-1 interacts with different components of the extracellular matrix, i.e. fibrin, heparin (Hep) and vitronectin (Vn). PAI-1 binding to Vn facilitates migration and invasion of tumor cells. The most important determinants of the Vn-binding site of PAI-1 appear to reside between amino acids 110-147, which includes alpha helix E (hE, amino acids 109-118). Ten different PAI-1 variants (mostly harboring modifications in hE) as well as wild-type PAI-1, the previously described PAI-1 mutant Q123K, and another serpin, PAI-2, were recombinantly produced in Escherichia coli containing a His(6) tag and purified by affinity chromatography. As shown in microtiter plate based binding assays, surface plasmon resonance and thrombin inhibition experiments, all of the newly generated mutants which retained inhibitory activity against uPA still bound to Vn. Mutant A114-118, in which all amino-acids at positions 114-118 of PAI-1 were exchanged for alanine, displayed a reduced affinity to Vn as compared to wild-type PAI-1. Mutants lacking inhibitory activity towards uPA did not bind to Vn. Q123K, which inhibits uPA but does not bind to Vn, served as a control. In contrast to other active PAI-1 mutants, the inhibitory properties of A114-118 towards thrombin as well as uPA were significantly reduced in the presence of Hep. Our results demonstrate that the wild-type sequence of the region around hE in PAI-1 is not a prerequisite for binding to Vn. PMID- 11784314 TI - The alpha 1 beta 1 contact of human hemoglobin plays a key role in stabilizing the bound dioxygen. AB - When the alpha and beta chains were separated from human oxyhemoglobin (HbO(2)), each individual chain was oxidized easily to the ferric form, their rates being almost the same with a very strong acid-catalysis. In the HbO(2) tetramer, on the other hand, both chains become considerably resistant to autoxidation over a wide range of pH values (pH 5-11). Moreover, HbA showed a biphasic autoxidation curve containing the two rate constants, i.e. k(f) for the fast oxidation due to the alpha chains, and k(s) for the slow oxidation to the beta chains. The k(f)/k(s) ratio increased from 3.2 at pH 7.5-7.3 at pH 5.8, but became 1 : 1 at pH values higher than 8.5. In the present work, we used the valency hybrid tetramers such as (alpha(3+))2(beta O(2))(2) and (alpha O(2)(2)(beta(3+))(2), and demonstrated that the autoxidation rate of either the alpha or beta chains (when O2- ligated) is independent of the valency state of the corresponding counterpart chains. From these results, we have concluded that the formation of the alpha 1 beta 1 or alpha 2 beta 2 contact suppresses remarkably the autoxidation rate of the beta chain and thus plays a key role in stabilizing the HbO(2) tetramer. Its mechanistic details were also given in terms of a nucleophilic displacement of O(2)(-) from the FeO(2) center, and the emphasis was placed on the proton catalyzed process performed by the distal histidine residue. PMID- 11784315 TI - A comparison of the urea-induced unfolding of apoflavodoxin and flavodoxin from Desulfovibrio vulgaris. AB - The kinetics and thermodynamics of the urea-induced unfolding of flavodoxin and apoflavodoxin from Desulfovibrio vulgaris were investigated by measuring changes in flavin and protein fluorescence. The reaction of urea with flavodoxin is up to 5000 times slower than the reaction with the apoprotein (0.67 s(-1) in 3 m urea in 25 mm sodium phosphate at 25 degrees C), and it results in the dissociation of FMN. The rate of unfolding of apoflavodoxin depends on the urea concentration, while the reaction with the holoprotein is independent of urea. The rates decrease in high salt with the greater effect occurring with apoprotein. The fluorescence changes fit two-state models for unfolding, but they do not exclude the possibility of intermediates. Calculation suggests that 21% and 30% of the amino-acid side chains become exposed to solvent during unfolding of flavodoxin and apoflavodoxin, respectively. The equilibrium unfolding curves move to greater concentrations of urea with increase of ionic strength. This effect is larger with phosphate than with chloride, and with apoflavodoxin than with flavodoxin. In low salt the conformational stability of the holoprotein is greater than that of apoflavodoxin, but in high salt the relative stabilities are reversed. It is calculated that two ions are released during unfolding of the apoprotein. It is concluded that the urea-dependent unfolding of flavodoxin from D. vulgaris occurs because apoprotein in equilibrium with FMN and holoprotein unfolds and shifts the equilibrium so that flavodoxin dissociates. Small changes in flavin fluorescence occur at low concentrations of urea and these may reflect binding of urea to the holoprotein. PMID- 11784316 TI - Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes. AB - Mammalian alcohol dehydrogenases (ADH) form a complex enzyme system based on amino-acid sequence, functional properties, and gene expression pattern. At least four mouse Adh genes are known to encode different enzyme classes that share less than 60% amino-acid sequence identity. Two ADH-containing and overlapping C57BL/6 bacterial artificial chromosome clones, RP23-393J8 and -463H24, were identified in a library screen, physically mapped, and sequenced. The gene order in the complex and two new mouse genes, Adh5a and Adh5b, and a pseudogene, Adh5ps, were obtained from the physical map and sequence. The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I-V, the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene. PMID- 11784317 TI - Functional assignment of motifs conserved in beta 1,3-glycosyltransferases. AB - The beta 1,3-glycosyltransferase enzymes identified to date share several conserved regions and conserved cysteine residues, all being located in the putative catalytic domain. To investigate the importance of these motifs and cysteines for the enzymatic activity, 14 mutants of the murine beta 1,3 galactosyltransferase-I gene were constructed and expressed in Sf9 insect cells. Seven mutations abolished the galactosyltransferase activity. Kinetic analysis of the other seven active mutants revealed that three of them showed a threefold to 21-fold higher apparent K(m) with regard to the donor substrate UDP-galactose relative to the wild-type enzyme, while two mutants had a sixfold to 7.5-fold increase of the apparent K(m) value for the acceptor substrate N acetylglucosamine-beta-p-nitrophenol. Taken together, our results indicate that the conserved residues W101 and W162 are involved in the binding of the UDP galactose donor, the residue W315 in the binding of the N-acetylglucosamine-beta p-nitrophenol acceptor, and the domain including E264 appears to participate in the binding of both substrates. PMID- 11784318 TI - The plant S-adenosyl-L-methionine:Mg-protoporphyrin IX methyltransferase is located in both envelope and thylakoid chloroplast membranes. AB - Chlorophyll biosynthesis requires a metabolic dialog between the chloroplast envelope and thylakoids where biosynthetic activities are localized. Here, we report the first plant S-adenosyl-l-methionine:Mg-protoporphyrin IX methyltransferase (MgP(IX)MT) sequence identified in the Arabidopsis genome owing to its similarity with the Synechocystis sp. MgP(IX)MT gene. After expression in Escherichia coli, the recombinant Arabidopsis thaliana cDNA was shown to encode a protein having MgP(IX)MT activity. The full-length polypeptide exhibits a chloroplast transit peptide that is processed during import into the chloroplast. The mature protein contains two functional regions. The C-terminal part aligns with the Synechocystis full-length protein. The corresponding truncated region binds to Ado-met, as assayed by UV crosslinking, and is shown to harbor the MgP(IX)MT activity. Downstream of the cleaved transit peptide, the 40 N-terminal amino acids of the mature protein are very hydrophobic and enhance the association of the protein with the membrane. In A. thaliana and spinach, the MgP(IX)MT protein has a dual localization in chloroplast envelope membranes as well as in thylakoids. The protein is active in each membrane and has the same apparent size corresponding to the processed mature protein. The protein is very likely a monotopic membrane protein embedded within one leaflet of the membrane as indicated by ionic and alkaline extraction of each membrane. The rationale for a dual localization of the protein in the chloroplast is discussed. PMID- 11784319 TI - Functional expression of human liver cytosolic beta-glucosidase in Pichia pastoris. Insights into its role in the metabolism of dietary glucosides. AB - Human tissues such as liver, small intestine, spleen and kidney contain a cytosolic beta-glucosidase (CBG) that hydrolyses various beta-d-glycosides, but whose physiological function is not known. Here, we describe the first heterologous expression of human CBG, a system that facilitated a detailed assessment of the enzyme specificity towards dietary glycosides. A full-length CBG cDNA (cbg-1) was cloned from a human liver cDNA library and expressed in the methylotrophic yeast Pichia pastoris at a secretion yield of approximately 10 mg x L-1. The recombinant CBG (reCBG) was purified from the supernatant using a single chromatography step and was shown to be similar to the native enzyme isolated from human liver in terms of physical properties and specific activity towards 4-nitrophenyl-beta-D-glucoside. Furthermore, the reCBG displayed a broad specificity with respect to the glycone moiety of various aryl-glycosides (beta-D fucosides, alpha-L-arabinosides, beta-D-glucosides, beta-D-galactosides, beta-L xylosides, beta-D-arabinosides), similar to the native enzyme. For the first time, we show that the human enzyme has significant activity towards many common dietary xenobiotics including glycosides of phytoestrogens, flavonoids, simple phenolics and cyanogens with higher apparent affinities (K(m)) and specificities (k(cat)/K(m)) for dietary xenobiotics than for other aryl-glycosides. These data indicate that human CBG hydrolyses a broad range of dietary glucosides and may play a critical role in xenobiotic metabolism. PMID- 11784320 TI - Molecular cloning, bacterial expression and properties of Rab31 and Rab32. AB - GTP-binding proteins of the Rab family were cloned from human platelets using RT PCR. Clones corresponding to two novel Rab proteins, Rab31 and Rab32, and to Rab11A, which had not been detected in platelets previously, were isolated. The coding sequence of Rab31 (GenBank accession no. U59877) corresponded to a 194 amino-acid protein of 21.6 kDa. The Rab32 sequence was extended to 1000 nucleotides including 630 nucleotides of coding sequence (GenBank accession no. U59878) but the 5' coding sequence was only completed later by others (GenBank accession no. U71127). Human Rab32 cDNA encodes a 225 amino-acid protein of 25.0 kDa with the unusual GTP-binding sequence DIAGQE in place of DTAGQE. Northern blots for Rab31 and Rab32 identified 4.4 kb and 1.35 kb mRNA species, respectively, in some human tissues and in human erythroleukemia (HEL) cells. Rabbit polyclonal anti-peptide antibodies to Rab31, Rab32 and Rab11A detected platelet proteins of 22 kDa, 28 kDa and 26 kDa, respectively. Human platelets were highly enriched in Rab11A (0.85 microg x mg of platelet protein(-1)) and contained substantial amounts of Rab32 (0.11 microg x mg protein(-1)). Little Rab31 was present (0.005 microg x mg protein(-1)). All three Rab proteins were found in both granule and membrane fractions from platelets. In rat platelets, the 28-kDa Rab32 was replaced by a 52-kDa immunoreactive protein. Rab31 and Rab32, expressed as glutathione S-transferase (GST)-fusion proteins, did not bind [alpha-(32)P]GTP on nitrocellulose blots but did bind [(35)S]GTP[S] in a Mg(2+) dependent manner. Binding of [(35)S]GTP[S] was optimal with 5 microm Mg(2+)(free) and was markedly inhibited by higher Mg(2+) concentrations in the case of GST Rab31 but not GST-Rab32. Both proteins displayed low steady-state GTPase activities, which were not inhibited by mutations (Rab31(Q64L) and Rab32(Q85L)) that abolish the GTPase activities of most low-M(r) GTP-binding proteins. PMID- 11784321 TI - Isolation and characterization of a thioredoxin-dependent peroxidase from Chlamydomonas reinhardtii. AB - All living organisms contain redox systems involving thioredoxins (Trx), proteins featuring an extremely conserved and reactive active site that perform thiol disulfide interchanges with disulfide bridges of target proteins. In photosynthetic organisms, numerous isoforms of Trx coexist, as revealed by sequencing of Arabidopsis genome. The specific functions of many of them are still unknown. In an attempt to find new molecular targets of Trx in Chlamydomonas reinhardtii, an affinity column carrying a cytosolic Trx h mutated at the less reactive cysteine of its active site was used to trap Chlamydomonas proteins that form mixed disulfides with Trx. The major protein bound to the column was identified by amino-acid sequencing and mass spectrometry as a thioredoxin-dependent 2Cys peroxidase. Isolation and sequencing of its gene revealed that this peroxidase is most likely a chloroplast protein with a high homology to plant 2Cys peroxiredoxins. It is shown that the Chlamydomonas peroxiredoxin (Ch-Prx1) is active with various thioredoxin isoforms, functions as an antioxidant toward reactive oxygen species (ROS), and protects DNA against ROS induced degradation. Expression of the peroxidase gene in Chlamydomonas was found to be regulated by light, oxygen concentration, and redox state. The data suggest a role for the Chlamydomonas Prx in ROS detoxification in the chloroplast. PMID- 11784322 TI - Cloning and expression of sterol Delta 14-reductase from bovine liver. AB - Biosynthesis of cholesterol represents one of the fundamental cellular metabolic processes. Sterol Delta 14-reductase (Delta 14-SR) is a microsomal enzyme involved in the conversion of lanosterol to cholesterol in mammals. Amino-acid sequence analysis of a 38-kDa protein purified from bovine liver in our laboratory revealed > 90% similarity with a human sterol reductase, SR-1, encoded by the TM7SF2 gene, and with the C-terminal domain of human lamin B receptor. A cDNA encoding the 38-kDa protein, similar to human TM7SF2, was identified by analysis of a bovine expressed sequence tag (EST) database. The cDNA was synthesized by RT-PCR, cloned, and sequenced. The cDNA encodes a 418 amino-acid polypeptide with nine predicted transmembrane domains. The deduced amino-acid sequence exhibits high similarity with Delta 14-SR from yeasts, fungi, and plants (55-59%), suggesting that the bovine cDNA encodes Delta 14-SR. Northern blot analysis of bovine tissues showed high expression of mRNA in liver and brain. The polypeptide encoded by the cloned cDNA was expressed in COS-7 cells. Immunofluorescence analysis of transfected cells revealed a distribution of the protein throughout the ER. COS-7 cells expressing the protein exhibited Delta 14 SR activity about sevenfold higher than control cells. These results demonstrate that the cloned bovine cDNA encodes Delta 14-SR and provide evidence that the human TM7SF2 gene encodes Delta 14-SR. PMID- 11784323 TI - Evaluation of two biosynthetic pathways to delta-aminolevulinic acid in Euglena gracilis. AB - delta-Aminolevulinic acid (ALA), which is an intermediate in the biosynthesis of chlorophyll a, can be biosynthesized via the C5 pathway and the Shemin pathway in Euglena gracilis. Analysis of the (13)C-NMR spectrum of (13)C-labeled methyl pheophorbide a, derived from 13C-labeled chlorophyll a biosynthesized from d-[1 (13)C]glucose by E. gracilis, provided evidence suggesting that ALA incorporated in the (13)C-labeled chlorophyll a was synthesized via both the C5 pathway and the Shemin pathway in a ratio of between 1.5 and 1.7 to one. The methoxyl carbon of the methoxycarbonyl group at C-132 of chlorophyll a was labeled with (13)C. The phytyl moiety of chlorophyll a was labeled on C-P2, C-P3(1), C-P4, C-P6, C P7(1), C-P8, C-P10, C-P11(1), C-P12, C-P14, C-P15(1) and C-P16. PMID- 11784324 TI - Disulfide bond formation through Cys186 facilitates functionally relevant dimerization of trimeric hyaluronan-binding protein 1 (HABP1)/p32/gC1qR. AB - Hyaluronan-binding protein 1 (HABP1), a ubiquitous multifunctional protein, interacts with hyaluronan, globular head of complement component 1q (gC1q), and clustered mannose and has been shown to be involved in cell signalling. In vitro, this recombinant protein isolated from human fibroblast exists in different oligomeric forms, as is evident from the results of various independent techniques in near-physiological conditions. As shown by size-exclusion chromatography under various conditions and glutaraldehyde cross-linking, HABP1 exists as a noncovalently associated trimer in equilibrium with a small fraction of a covalently linked dimer of trimers, i.e. a hexamer. The formation of a covalently-linked hexamer of HABP1 through Cys186 as a dimer of trimers is achieved by thiol group oxidation, which can be blocked by modification of Cys186. The gradual structural transition caused by cysteine-mediated disulfide linkage is evident as the fluorescence intensity increases with increasing Hg(2+) concentration until all the HABP1 trimer is converted into hexamer. In order to understand the functional implication of these transitions, we examined the affinity of the hexamer for different ligands. The hexamer shows enhanced affinity for hyaluronan, gC1q, and mannosylated BSA compared with the trimeric form. Our data, analyzed with reference to the HABP1/p32 crystal structure, suggest that the oligomerization state and the compactness of its structure are factors that regulate its function. PMID- 11784325 TI - Growth inhibition of mammalian cells by eosinophil cationic protein. AB - Eosinophil cationic protein (ECP), one of the major components of basic granules of eosinophils, is cytotoxic to tracheal epithelium. However, the extent of this effect on other cell types has not been evaluated in vitro. In this study, we evaluated the effect of ECP on 13 mammalian cell lines. ECP inhibited the growth of several cell lines including those derived from carcinoma and leukemia in a dose-dependent manner. The IC(50) values on A431 cells, MDA-MB-453 cells, HL-60 cells and K562 cells were estimated to be approximately 1-5 microm. ECP significantly suppressed the size of colonies of A431 cells, and decreased K562 cells in G1/G0 phase. However, there was little evidence that ECP killed cells in either cell line. These effects of ECP were not enhanced by extending its N terminus. Rhodamine B isothiocyanate-labeled ECP started to bind to A431 cells after 0.5 h and accumulated for up to 24 h, indicating that specific affinity for the cell surface may be important. The affinity of ECP for heparin was assessed and found to be reduced when tryptophan residues, one of which is located at a position in the catalytic subsite of ribonuclease in ECP, were modified. The growth-inhibitory effect was also attenuated by this modification. These results suggest that growth inhibition by ECP is dependent on cell type and is cytostatic. PMID- 11784326 TI - Induction of chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI ) gene expression is mediated by ETS factor binding sites. AB - Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI, or NR2F1) is an orphan nuclear receptor that plays a major role in the development of the nervous system. We show here that three ETS response elements in the COUP-TFI promoter mediate its transcription. A reporter gene containing these ETS binding sites is activated by Ets-1, while the same reporter with point mutations on all three ETS response elements is not. We also show that Ets-1 binds to these response elements and that other ETS factors also transactivate the COUP-TFI promoter. In addition, COUP-TFI is coexpressed with some ETS factors in the mouse embryo. These results indicate that members of the ETS family can activate COUP TFI gene expression. PMID- 11784327 TI - An alternative model for photosystem II/light harvesting complex II in grana membranes based on cryo-electron microscopy studies. AB - The photosynthetic protein complexes in plants are located in the chloroplast thylakoid membranes. These membranes have an ultrastructure that consists of tightly stacked 'grana' regions interconnected by unstacked membrane regions. The structure of isolated grana membranes has been studied here by cryo-electron microscopy. The data reveals an unusual arrangement of the photosynthetic protein complexes, staggered over two tightly stacked planes. Chaotrope treatment of the paired grana membranes has allowed the separation and isolation of two biochemically distinct membrane fractions. These data have led us to an alternative model of the ultrastructure of the grana where segregation exists within the grana itself. This arrangement would change the existing view of plant photosynthesis, and suggests potential links between cyanobacterial and plant photosystem II light harvesting systems. PMID- 11784328 TI - Early growth response-1 gene (Egr-1) promoter induction by ionizing radiation in U87 malignant glioma cells in vitro. AB - The promoter of the early growth response gene (Egr-1) has been described to be activated by ionizing radiation, and it seems to be clear that this process involves different mitogen activated protein (MAP) kinases, dependent on the specific cell type examined. However, early steps leading to activation of the corresponding pathways and thus to overexpression of Egr-1 are not well understood. In this study, deletion mutants of the 5' upstream region of the Egr 1 gene were generated which allowed us to correlate the radiation-induction of the Egr-1 promoter in U87 glioma cells to five serum response elements. Based on the data shown, a possible role of two cAMP responsive elements for radiation dependent promoter regulation could be ruled out. On the basis of activator/inhibitor studies applying fetal bovine serum, EGF, PD98059, anisomycin, SB203580, forskolin and wortmannin, it could be demonstrated that in U87 cells the ERK1/2 and potentially SAPK/JNK, but not the p38MAPK/SAPK2, pathway contribute to the radiation-induction of Egr-1 promoter. In addition, it was observed that irradiated cells secrete a diffusible factor into the culture media which accounts for the radiation-induced promoter upregulation. By blocking growth factor receptor activation with suramin, this effect could be completely abolished. PMID- 11784329 TI - A beta-lysine adenylating enzyme and a beta-lysine binding protein involved in poly beta-lysine chain assembly in nourseothricin synthesis in Streptomyces noursei. AB - Nourseothricins (syn. Streptothricins), a group of nucleoside peptides produced by several streptomycete strains, contain a poly beta-lysine chain of variable length attached in amide linkage to the amino sugar moiety gulosamine of the nucleoside portion. We show that the nourseothricin-producing Streptomyces noursei contains an enzyme (NpsA) of an apparent M(r) 56,000 that specifically activates beta-lysine by adenylation but does not bind to it as a thioester. Cloning and sequencing of npsA from S. noursei including its flanking DNA regions revealed that it is closely linked to the nourseothricin resistance gene nat1 and some other genes on the chromosome possibly involved in nourseothricin biosynthesis. The deduced amino-acid sequence revealed that NpsA is a stand-alone adenylation domain with similarity to the adenylation domains of nonribosomal peptide synthetases (NRPS). Further analysis revealed that S. noursei contains a beta-lysine binding enzyme (NpsB) of about M(r) 64,100 which can be loaded by NpsA with beta-lysine as a thioester. Analysis of the deduced amino-acid sequence from the gene (npsB) of NpsB showed that it consists of two domains. The N terminal domain of approximately 100 amino-acid residues has high similarity to PCP domains of NRPSs whereas the 450-amino-acid C-terminal domain has a high similarity to epimerization (E)-domains of NRPSs. Remarkably, in this E-domain the conserved H-H-motif is changed to H-Q, which suggests that either the domain is nonfunctional or has a specialized function. The presence of one single adenylating beta-lysine activating enzyme in nourseothricin-producing streptomycete and a separate binding protein suggests an iteratively operating NRPS-module catalyses synthesis of the poly beta-lysine chain. PMID- 11784330 TI - Structural and serological relatedness of the O-antigens of Proteus penneri 1 and 4 from a novel Proteus serogroup O72. AB - O-specific polysaccharides (O-antigens) of the lipopolysaccharides (LPS) of Proteus penneri strains 1 and 4 were studied using sugar analysis, (1)H and (13)C NMR spectroscopy, including 2D COSY, H-detected (1)H,(13)C HMQC, and rotating frame NOE spectroscopy (ROESY). The following structures of the tetrasaccharide (strain 1) and pentasaccharide (strain 4) repeating units of the polysaccharides were established: [reaction: see text]. In the polysaccharide of P. penneri strain 4, glycosylation with the lateral Glc residue (75%) and O-acetylation of the lateral GalNAc residue (55%) are nonstoichiometric. This polysaccharide contains also other, minor O-acetyl groups, whose positions were not determined. The structural similarity of the O-specific polysaccharides was consistent with the close serological relatedness of the LPS, which was demonstrated by immunochemical studies with O-antisera against P. penneri 1 and 4. Based on these data, it was proposed to classify P. penneri strains 1 and 4 into a new Proteus serogroup, O72, as two subgroups, O72a and O72a,b, respectively. Serological cross-reactivity of P. penneri 1 O-antiserum with the LPS of P. penneri 40 and 41 was substantiated by the presence of an epitope(s) on the LPS core region shared by all P. penneri strains studied. PMID- 11784331 TI - Fluorescence study of the high pressure-induced denaturation of skeletal muscle actin. AB - Ikkai & Ooi [Ikkai, T. & Ooi, T. (1966) Biochemistry 5, 1551-1560] made a thorough study of the effect of pressure on G- and F-actins. However, all of the measurements in their study were made after the release of pressure. In the present experiment in situ observations were attempted by using epsilon ATP to obtain further detailed kinetic and thermodynamic information about the behaviour of actin under pressure. The dissociation rate constants of nucleotides from actin molecules (the decay curve of the intensity of fluorescence of epsilon ATP G-actin or epsilon ADP-F-actin) followed first-order kinetics. The volume changes for the denaturation of G-actin and F-actin were estimated to be -72 mL x mol(-1) and -67 mL x mol(-1) in the presence of ATP, respectively. Changes in the intensity of fluorescence of F-actin whilst under pressure suggested that epsilon ADP-F-actin was initially depolymerized to epsilon ADP-G-actin; subsequently there was quick exchange of the epsilon ADP for free epsilon ATP, and then polymerization occurred again with the liberation of phosphate from epsilon ATP bound to G-actin in the presence of excess ATP. In the higher pressure range (> 250 MPa), the partial collapse of the three-dimensional structure of actin, which had been depolymerized under pressure, proceeded immediately after release of the nucleotide, so that it lost the ability to exchange bound ADP with external free ATP and so was denatured irreversibly. An experiment monitoring epsilon ATP fluorescence also demonstrated that, in the absence of Mg(2+)-ATP, the dissociation of actin-heavy meromyosin (HMM) complex into actin and HMM did not occur under high pressure. PMID- 11784332 TI - Propionate CoA-transferase from Clostridium propionicum. Cloning of gene and identification of glutamate 324 at the active site. AB - Propionate CoA-transferase from Clostridium propionicum has been purified and the gene encoding the enzyme has been cloned and sequenced. The enzyme was rapidly and irreversibly inactivated by sodium borohydride or hydroxylamine in the presence of propionyl-CoA. The reduction of the thiol ester between a catalytic site glutamate and CoA with borohydride and the cleavage by hydroxylamine were used to introduce a site-specific label, which was followed by MALDI-TOF-MS. This allowed the identification of glutamate 324 at the active site. Propionate CoA transferase and similar proteins deduced from the genomes of Escherichia coli, Staphylococcus aureus, Bacillus halodurans and Aeropyrum pernix are proposed to form a novel subclass of CoA-transferases. Secondary structure element predictions were generated and compared to known crystal structures in the databases. A high degree of structural similarity was observed between the arrangement of secondary structure elements in these proteins and glutaconate CoA transferase from Acidaminococcus fermentans. PMID- 11784333 TI - Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase. AB - Stimulation with granulocyte colony-stimulating factor (G-CSF) induces myeloid precursor cells to differentiate into neutrophils, and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However, the signaling pathways for neutrophil differentiation are still obscure. As the Src-like tyrosine kinase, Lyn, has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells, we examined its involvement in G-CSF induced signal transduction in mammalian cells. Expression plasmids for wild-type Lyn (Lyn) and kinase-negative Lyn (LynKN) were introduced into a murine granulocyte precursor cell line, GM-I62M, that can respond to G-CSF with neutrophil differentiation, and cell lines that overexpressed these molecules (GM Lyn, GM-LynKN) were established. Upon G-CSF stimulation, both the GM-Lyn and GM LynKN cells began to differentiate into neutrophils, showing early morphological changes within a few days, much more rapidly than did the parental cells, which started to exhibit nuclear lobulation about 10 days after the cells were transferred to G-CSF-containing medium. However, the time course of expression of the myeloperoxidase gene, another neutrophil differentiation marker, was not affected by the overexpression of Lyn or LynKN. Therefore, in normal cells, protein interactions with Lyn, but not its kinase activity, are important for the induction of G-CSF-induced neutrophilic nuclear lobulation in mammalian granulopoiesis. PMID- 11784334 TI - Amidolytic activity of prostatic acid phosphatase on human semenogelins and semenogelin-derived synthetic substrates. AB - In addition to kallikrein hK3, a serine protease generally reported as PSA (prostate-specific antigen), at least two other enzymes in human seminal plasma also cleave synthetic peptidyl substrates derived from the sequence of human semenogelins. We have identified one of these as prostatic acid phosphatase (PAP), a major component of prostatic fluid whose physiological function is unclear. The other is a high Mr basic protein present at low concentrations in seminal plasma and that remains to be characterized. PAP was purified to homogeneity from freshly ejaculated seminal plasma. Its N-terminal sequence and its phosphatase properties (hydrolysis of para-nitrophenylphosphate at low pH) were determined, and its inhibition by sodium fluoride measured. Both purified and commercial PAP also had amidolytic activity on peptide substrates derived from the semenogelin sequence at neutral and slightly basic pH. The k(cat)/K(m) values were in the 10(2)-10(3) m(-1) x s(-1) range using fluorogenic semenogelin derived substrates whose peptidyl moiety included cleavage sites that had been identified ex vivo. PAP cleavage sites differed from those of hK3 and were mainly at P1 = Gln residues or between residues bearing hydroxyl groups. PAP amidolytic activity was poorly inhibited by all currently used wide spectrum proteinase inhibitors. Only 3-4 dichloroisocoumarin and benzamidine inhibited purified PAP. Purified human semenogelin was cleaved by purified and commercial PAP at neutral pH; the two main cleavage sites were at Tyr292 and Ser170 (semenogelin I sequence), only the former has been identified ex vivo by analysis of seminal plasma. PMID- 11784335 TI - Recent advances in the diagnosis and treatment of epilepsy. AB - Recent advances in the diagnosis and treatment of epilepsies are discussed with special consideration of epidemiology and classification, progress in neuroimaging, electrophysiological studies using EEG and MEG, initiation of medical and surgical treatment, the role of new antiepileptic drugs and selected aspects of genetics of idiopathic epilepsies. In addition from conclusions obtained by the review of recent developments suggestions for future work in Europe are discussed. A constructive approach from multicenter studies requires homologous definitions, documentations and standardization of procedures of trials for European multicenter studies. PMID- 11784336 TI - EFNS Task Force on Teaching of Neuroimaging in Neurology Curricula in Europe: present status and recommendations for the future. AB - A Task Force on 'Teaching of Neuroimaging in Neurology Curricula in Europe' was appointed in September 1998 by the education committee of the European Federation of Neurological Societies (EFNS) in order to: (1) examine the present status of teaching of neuroimaging in the training of neurology in European countries, and, in particular, to assess the strengths and weaknesses of the various countries; (2) give recommendations for global improvement and harmonization of such training. A questionnaire was completed in February 1999 and sent to 35 delegates of national neurological societies. Completed questionnaires were received from 21 countries: Albania, Austria, Croatia, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Switzerland, Turkey and UK. The questionnaire revealed that the situation in Europe is highly heterogeneous, both as regards the training in neurology in general and, more specifically, the teaching of neuroimaging during the training. Some recommendations to make the teaching of neuroimaging more homogeneous across European countries and to improve it are provided. PMID- 11784337 TI - Guidance for the preparation of neurological management guidelines by EFNS scientific task forces. AB - The aim of an EFNS neurological management guideline is to provide guidance for clinical neurologists, other health care professionals and health care providers about important aspects of management of neurological disease. It represents the view of an expert task force appointed by the chairperson of the scientific committee with the agreement of the chairperson of a Scientist Panel. It will be a peer-reviewed statement of minimum desirable standards for the guidance of practice based on the best available evidence. It is not intended to have legally binding implications in individual cases. PMID- 11784338 TI - Postgraduate education in neurology in Central and Eastern Europe. AB - The policy of the European co-operation in the new atmosphere of an international solidarity became one of the priorities of the European Federation of Neurological Societies (EFNS). It could be hardly pursued more efficiently in any other field of neurological performance as in education. To review several aspects of neurological practice and education the 'First European Co-operation Neurology Workshop' was held in the castle of Trest', Czech Republic, 13-20 April 2000. Participants from 15 countries (Albania, Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Moldova, Poland, Romania, Russia, Slovak Republic and Slovenia), covering a region of 316 million inhabitants and 25 000 neurologists, presented their national postgraduate education systems (besides other topics). We refer data on density of medical doctors and that of neurologists, pre-board certification phase, board examination, continuing medical education (CME), and qualification rewards. Illustrative data were put in the comparative tables. This first meeting has founded the basis for a dynamic future collaboration in order to continue the integration process and an exchange of current information regarding CME amongst central and eastern countries as well as western Europe. PMID- 11784340 TI - Treatment of relative sialorrhoea with botulinum toxin type A: description and rationale for an injection procedure with case report. AB - This paper describes a technique for treatment of relative sialorrhoea by injection of botulinum toxin type A. It includes the rationale for treatment, a description of the regional anatomy, the physiological basis for treatment and the applied pharmacology of the drug. Included also is a case report which is intended to provide an illustration of the benefits of using this method for treating this condition. PMID- 11784339 TI - A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. AB - OBJECTIVE: To study the efficacy and safety of botulinum toxin type A (BtxA) in the treatment of upper limb muscle spasticity, caused by stroke. METHODS: This was a randomized, controlled trial. Patients received either placebo injections or a total of 1000 IU of BtxA (Dysport) into five muscles of the affected arm. Muscle tone was assessed using the Modified Ashworth Scale (MAS). Other outcome measures were the change in the joint range of motion (ROM), the Barthel index, pain score, goal attainment and the subjective evaluation of benefit by patients and investigators. The patients were assessed blind to randomization at baseline and 4, 8, 12 and 16 weeks after treatment. RESULTS: Fifty nine patients were recruited and received treatment. One patient was lost to follow-up before the last scheduled visit of the study. The group of patients who received BtxA had a significant reduction in the summed MAS score at week 4 compared with the placebo group (P=0.004). The magnitude of benefit over the 16 week follow-up period was significantly reduced for the BtxA group in the wrist (P=0.004) and the finger joints (P=0.001) when compared with the placebo. There was no statistically significant difference between the groups in the joint ROM, muscle pain, goal attainment or the Barthel index scores at week 4 of the study. At week 16, the BtxA group showed significantly greater improvement in the passive ROM at the elbow (P=0.036). The patients' global assessment of benefit at the end of the study showed that 16 (50%) patients in the placebo group had 'much improved' or had 'some improvement' compared with 24 (92.3%) patients in the BtxA group (P=0.007). The investigators' rating for the same item was 16 (50%) and 23 (88.4%) patients, respectively (P=0.002). Sixteen and twenty patients in the BtxA and placebo groups, respectively, had an adverse event. The most frequently reported adverse events were accidental injury, respiratory and urinary tract infections and muscle pain. CONCLUSION: The findings of the present study suggest that treatment with BtxA in a dose of 1000 units reduces muscle tone in patients with post-stroke upper limb spasticity. This effect is sustained for at least 16 weeks. BtxA is safe in the dose used in this study. IMPORTANT NOTE: The authors wish to emphasize that the botulinum toxin preparation used in this study was Dysport (Ipsen Ltd) which has a different therapeutic equivalence from other commercially available product, Botox (Allergan Inc.). PMID- 11784341 TI - Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes. AB - It has been suggested that proton magnetic resonance spectroscopy (MRS) of the striatum can differentiate between parkinsonian syndromes. The present study aims to examine this claim by performing a systematic review of the existing literature. A MEDLINE search was performed between 1966 and October 1999, along with searches of conference abstracts and reference lists of papers identified. Eleven groups have used MRS to examine metabolite ratios in the striatum in Parkinsonian syndromes. A number of these have shown reduced N acetylaspartate/choline (NAA/Cho) and/or N-acetylaspartate/creatine (NAA/Cr) ratios in either idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration. However, the heterogeneity in the results precludes the use of any of these findings in differential diagnosis at the present time. The only group to use absolute metabolite concentrations rather than ratios showed that the decreased NAA/Cho ratio in IPD was because of an increase in choline which is of uncertain biological significance. Further large multicentre trials are required using absolute quantitation of tissue metabolite concentrations and a standardized technique. The patients entering such studies must be rigorously assessed to establish the diagnosis of the type of parkinsonism as accurately as possible. Any discriminatory abnormality must be tested in a large prospective study of newly presenting parkinsonian patients with long-term clinical follow up and ultimate pathological confirmation of the diagnosis as far as possible. PMID- 11784342 TI - Bilateral GPi DBS is useful to reduce abnormal involuntary movements in advanced Parkinson's disease patients, but its action is related to modality and site of stimulation. AB - In Parkinson's disease (PD) patients, internal globus pallidus (GPi) stimulation has been reported to produce good effects on abnormal involuntary movements (AIM); less improvement has been observed in extrapyramidal symptoms. We assessed the effect of monopolar dorsal (uppermost), ventral (lowest) and bipolar (uppermost vs. lowest) bilateral globus pallidus stimulation by quadripolar electrode on extrapyramidal symptoms and AIM induced by a dose of apomorphine. Six PD patients were studied in OFF therapy condition after surgery without stimulation (STIM OFF) and during stimulation (STIM ON) with the three different modalities. All patients were evaluated by the unified Parkinson's disease rating scale, section III (UPDRS) and by the AIM. Our results show that all three bilateral GPi stimulation modalities reduce the UPDRS score (between 49.7 and 31.5%), although the bipolar and lowest stimulation are the most effective. Similarly, bipolar and lowest stimulation were also the most effective in reducing the occurrence and intensity of the apomorphine-induced AIM. On the contrary, uppermost stimulation (UP ON) produced an AIM occurrence similar to that observed in the OFF stimulus condition. We suggest that bilateral GPi stimulation is an useful procedure to ameliorate extrapyramidal signs of advanced PD patients; however, it produces an antidyskinetic effect only if the ventral or the entire GPi is stimulated. On the contrary, the UP ON, most probably located in the external globus pallidus (GPe), does not modify the AIM occurrence. PMID- 11784343 TI - Cognitive response control in writer's cramp. AB - Disturbances of the motor and sensory system as well as an alteration of the preparation of movements have been reported to play a role in the pathogenesis of dystonias. However, it is unclear whether higher aspects of cortical - like cognitive - functions are also involved. Recently, the NoGo-anteriorization (NGA) elicited with a visual continuous performance test (CPT) during recording of a 21 channel electroencephalogram has been proposed as an electrophysiological standard-index for cognitive response control. The NGA consists of a more anterior location of the positive area of the brain electrical field associated with the inhibition (NoGo-condition) compared with that of the execution (Go condition) of a prepared motor response in the CPT. This response control paradigm was applied in 16 patients with writer's cramp (WC) and 14 age matched healthy controls. Topographical analysis of the associated event-related potentials revealed a significant (P < 0.05) NGA effect for both patients and controls. Moreover, patients with WC showed a significantly higher global field power value (P < 0.05) in the Go-condition and a significantly higher difference amplitude (P < 0.05) in the NoGo-condition. A source location analysis with the low resolution electromagnetic tomography (LORETA) method demonstrated a hypoactivity for the Go-condition in the parietal cortex of the right hemisphere and a hyperactivity in the NoGo-condition in the left parietal cortex in patients with WC compared with healthy controls. These results indicate an altered response control in patients with WC in widespread cortical brain areas and therefore support the hypothesis that the pathogenesis of WC is not restricted to a pure sensory-motor dysfunction. PMID- 11784344 TI - The prevalence of dementia and cognitive deficit in a rural population of 2442 residents in northern Italy. A door-to-door survey. AB - A population study to estimate the prevalence of dementia was carried out amongst the residents of four rural towns near Pavia in northern Italy. The population included a 40% sample of the residents between 65 and 69 years old and all residents of 70 years old or older. A door-to-door neuropsychological screening was followed by neurological examination on individuals scoring low at the screening. Of the 1670 subjects who completed the screening, 42.3% scored under the cut-off point. The prevalence of cognitive deficit was higher in women, even accounting for age. Of those who scored under the cut-off point, 336 underwent neurological examination, yielding a prevalence of dementia of 15% (from 1.6% between the ages of 65 and 69; 35% at the age of 85) in women and 5% (from 7% between the ages of 75 and 79; 27% at the age of 85 or more) in men. PMID- 11784345 TI - Idiopathic normal-pressure hydrocephalus: evaluation and findings in a multidisciplinary memory clinic. AB - The diagnostic evaluation of patients with possible idiopathic normal-pressure hydrocephalus (INPH) is traditionally performed in the settings of either neurological, neurosurgical or psychiatric departments. The diagnostic procedure and findings in 71 consecutive patients referred with a clinical and radiological suspicion of INPH to our out-patient multidisciplinary memory clinic are evaluated. Primary diagnoses and potential concomitant disorders considered of secondary importance for the symptomatologies were established. Abnormal hydrodynamics, demonstrated by intraventricular pressure monitoring and infusion test were mandatory for the diagnosis of INPH. Mean age was 68 years and mean Mini-Mental State Examination (MMSE) score was 22. DSM IV criteria of dementia were fulfilled in 42%. In half of the referred patients (n=36), the suspicion of INPH was already disproved subsequently to the evaluation programme performed in the outpatient clinic. The main primary diagnosis was cerebrovascular disease (CVD) comprising 27% (n=19) of the referrals, whereas INPH was diagnosed in only 20% (n=14). Shunt improvement rate was 72%. The remaining patients were diagnosed as having one of 26 different conditions. A multiplicity of disorders mimics the INPH syndrome, with CVD being the primary differential diagnosis. Evaluating patients with possible INPH in an outpatient multidisciplinary memory clinic is an effective and rational diagnostic approach. PMID- 11784346 TI - The perception of memory failures in patients with epilepsy. AB - The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population. We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50). A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests. Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05). It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception. PMID- 11784347 TI - Dementia and cognitive impairment three months after stroke. AB - To investigate the cognitive capacities of a cohort of ischaemic or haemorrhagic stroke survivors and to identify the clinical determinants of post-stroke cognitive impairment, we evaluated 237 patients admitted to a Stroke Unit (mean age 59; SD=12.7). Three months after stroke, patients were submitted to a neuropsychological evaluation that included the Mini-Mental State Examination (MMSE), a complementary battery to assess specific cognitive domains, the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale (BDS). Disturbed performance on at least one domain was detected on 131 (55%) patients: 27% had cognitive deficits other than memory, 7% had focal memory deficit, 9% had memory and other cognitive deficits and 6% had dementia. Dementia was associated with female gender (P=0.01), older age (P=0.01) and lower education level (P=0.04). Patients with memory deficits were older (P=0.01) with lower educational level (P=0.08) and more left sided lesions (P=0.02) than patients without memory deficits. In this middle aged stroke survivors cognitive impairment was common 3 months after stroke, while dementia was infrequent. PMID- 11784348 TI - Disorders in intentional gestural organization in Alzheimer's disease: combined or selective impairment of the conceptual and production systems? AB - This study examines disorders which affect the intentional gestural organization in Alzheimer's disease. An original and prospective protocol which assessed both the conceptual and production systems (with reference to the Roy and Square model 1985) was presented to 16 patients with Alzheimer's disease (mild to moderate dementia) and 40 healthy elderly subjects. Our study showed impairment of both systems in the Alzheimer's patients group. Two patients presented reverse performance profiles, which were characterized in one case by preservation of the conceptual system and impairment of the production system and in the other by the reverse dissociation. The findings demonstrated that disorders in the intentional gestural organization in Alzheimer's disease usually affect both the conceptual and production systems. The hypothesis concerning the existence of two functionally distinct systems underlying the organization of intentional body movement was corroborated (1) by a lack of significant correlation between the scores obtained in the assessment of the two systems and (2) by the demonstration of the double dissociation. PMID- 11784349 TI - The many faces of crossed aphasia in dextrals: report of nine cases and review of the literature. AB - A substantial body of the aphasia literature has been devoted to the topic of crossed aphasia in dextrals (CAD) over the past century but still no theory exists that explains the anomalous organization of neurocognitive functions in this population. However, if strict selection criteria are applied only some cases of vascular CAD are reported in which the correlation between neurocognitive disturbances and the locus of the brain lesion is studied. This study describes nine new cases of vascular CAD who underwent in-depth neurolinguistic and neuropsychological investigations. Our analysis shows the semiological variability of CAD phenomena and the many faces of the lesion behaviour relationships of this exceptional neurobiological condition. PMID- 11784350 TI - Acute cervical hyperextension-hyperflexion injury may precipitate and/or exacerbate symptomatic multiple sclerosis. AB - We report here 39 cases in which definite multiple sclerosis (MS) was precipitated or exacerbated by specific hyperextension-hyperflexion cervical cord trauma. The worsening or onset of the symptomatic disease bore a striking temporal relationship to the focal injury. Our data suggests that central nervous system (CNS)-specific acute physical trauma such as cervical cord hyperextension hyperflexion injury may aggravate latent clinical symptoms in MS. The deterioration of MS bore no direct relationship with the severity of neck injury. Possible pathogenic mechanisms of focal CNS-specific trauma aggravating the course of asymptomatic or benign MS are discussed. This may have implications in improving our understanding of the factors that may modify the clinical course of MS. PMID- 11784351 TI - Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis. AB - Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation. PMID- 11784352 TI - Encephalitis associated with motor polyneuropathy. AB - We describe three patients with acute encephalitis and motor-dominant polyneuropathy. All three patients were in their middle age and presented with features of encephalopathy with flu like illness. Cerebrospinal fluid (CSF) studies showed lymphocytic pleocytosis with increased protein. Brain magnetic resonance imagings (MRIs) showed symmetric high signal intensities in bilateral mesial temporal lobes and bilateral thalami in all patients. All three patients became quadriplegic and areflexic within two hospital days (HDs) and electrophysiologic studies revealed motor polyneuropathy. Viral or atypical bacterial infection was suspected, but no causative agent could be found. One patient expired on the twentieth hospital day, and the other two patients showed no or little improvement. To our knowledge, this combination of acute encephalitis with motor polyneuropathy has not been reported. PMID- 11784353 TI - Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis. AB - Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, alpha-tocopherol status is poor in myopathic alcoholics. Reduced alpha-tocopherol may pre-dispose the muscle to metabolic injury. However, experimental alpha-tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired alpha-tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover. PMID- 11784354 TI - Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions. AB - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5-Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein-22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51-year old patient with a l.5-Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure. PMID- 11784355 TI - Low headache prevalence amongst women with high TSH values. AB - The aim of this large cross-sectional population-based study was to examine a possible positive or negative association between thyroid dysfunction and headache. Between 1995 and 1997, all 92 566 adults in Nord-Trondelag County in Norway were invited to participate in a health survey. A total of 51 383 (56%) responded to a headache questionnaire, whereof thyroid-stimulating hormone (TSH) was measured in 28 058 individuals. These included 15 465 women and 8019 men above 40 years of age, 1767 randomly selected individuals between 20 and 40 years of age, and 2807 (97%) with thyroid dysfunction. Associations between thyroid dysfunction and headache were assessed in multivariate analyses, estimating prevalence odds ratios (OR) with 95% confidence intervals (CIs). High TSH values were associated with low prevalence of headache. This was most evident amongst women with no history of thyroid dysfunction. Amongst these, headache was less probable (OR=0.5, 95% CI 0.3-0.7) if TSH > or = 10 mU/l than in women with normal TSH (0.2-4 mU/l). In all age groups between 40 and 80 years, TSH was lower amongst headache sufferers, especially migraineurs, than in those without headache complaints. PMID- 11784356 TI - Hospitalization of patients with neurological disorders and estimation of the need of beds and of the related costs in Austria's non-profit hospitals. AB - In 1997, 273 722 hospitalizations as a result of neurological disorders, including the related operated cases, were reported in Austria's non-profit hospitals (80% of all hospitals). They represent 14.12% of all 1.9 million in patient treatments. The individual disease groups, e.g. cerebrovascular disorders (59 269 admissions or 3.06%), multiple sclerosis (3920 admissions or 0.2%) and all other groups are detailed. We estimated the cost resulting from these diseases which amounted to 11.88% of all hospital costs. We were also able to estimate that 5549 beds are required for in-patient treatment in the area of neurology, assuming an average duration of treatment of 8 days (Austrian mean value for neurological disorders). This is equivalent to one bed per 1367 inhabitants or 11.31% of all beds for in-patient treatment in non-profit hospitals in Austria. Obviously at present the majority of neurological patients are treated in non-neurological departments. A major increase in resources to neurology is necessary if patients are to receive the benefit of specialized diagnosis and treatment. These further resources not only cover the increase of neurological beds in hospitals but also financial, personal resources and in consequence increased capacity for neurological education, training and research. PMID- 11784357 TI - Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer's disease. AB - In order to assess the impact of traumatic brain injury (TBI) and Apolipoprotein E (ApoE) allele frequency on the development of Alzheimer's disease (AD), we examined: (i) the incidence of AD pathology in 55 consecutive autopsy cases (mean age +/- SD 77.6 +/- 7.3 years) with residual closed TBI lesions and (ii) the frequency of TBI residuals in 53 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. The results were as follows: (i) In the TBI series, 12.7% showed Consortium to Establish a Registry for Alzheimer's disease (CERAD) definite and 9.1% probable AD, only one with ApoEepsilon4. From the remaining 43 non-AD cases, three had ApoEepsilon4. The prevalence of 21.8% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over the age of 70. (ii) In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of TBI were seen in 4 brains (7.5%), all lacking the ApoEepsilon4 allele. TBI incidence was slightly higher than 8.5% in the clinical MIRAGE study. The results of this first retrospective autopsy study of TBI, ApoE allele frequency, and AD confirms clinical studies suggesting severe TBI to be a risk factor for the development of AD particularly in subjects lacking ApoEepsilon4. PMID- 11784358 TI - Hepatitis B vaccine related-myelitis? AB - We present four incidental cases that developed partial myelitis following the administration of hepatitis B vaccine in 1998. The first two cases, a 33-year-old man and a 42-year-old woman developed progressive sensory symptoms without motor involvement within 4 weeks following the vaccination. Their magnetic resonance imaging (MRI) disclosed similar lesions consistent with myelitis at their cervical spinal cord. A comparable inflammatory lesion was seen at the T9-T10 levels of the spinal cord in the third case, who was a 40-year-old woman presenting with numbness in her legs and urinary retention following the vaccination. The fourth case who was a 42-year-old woman, presented with sensory symptoms in her left extremities, which developed 3 months after the vaccination. Her MRI showed a hyperintense lesion at C6. She also had two tiny lesions in her cranial MRI. In all cases, there was no history of preceding infections and no clinical evidence suggestive of any other disorders that may cause myelopathy. All patients recovered completely within 3 months with the exception of the third patient who developed new neurological symptoms after 12 months. Similar clinical and imaging presentation of myelitis following hepatitis B vaccination within a 1 year period with no other demonstrable clinical and laboratory evidence for any other disorder raise the probability of a causal link between these two events. PMID- 11784359 TI - Neurofibromatosis and glioblastoma in a case of multiple sclerosis. AB - The case of a 37-year-old woman is presented. Cutaneous neurofibromatosis was associated with a progressive course of multiple sclerosis. Unexpectedly, autopsy revealed a right hemispheric glioblastoma which was silent during her life. PMID- 11784360 TI - Cerebral vasculitis and ischaemic stroke in Behcet's disease: report of one case and review of the literature. AB - INTRODUCTION: Behcet's disease (BD) is a multisystemic, recurrent, inflammatory disorder. Neurological involvement is well-known but cerebral vasculitis and ischaemic stroke are unusual. CASE DESCRIPTION: A 43-year-old male patient presented with acute left hemiparesis, he had recurrent oral aphthae and scrotal ulcerations. Two episodes of transient brainstem ischaemia and an episode of right hemiparesis were reported in the past 2 years. Cranial magnetic resonance (MR) imaging showed a right striatocapsular infarction and multiple segmental stenosis, fusiform enlargement and beading of the arteries of the polygone of Willis were seen on angiography. Cerebro-spinal fluid (CSF) examination disclosed lymphocytic pleocytosis. Skin pathergy test was positive. A diagnosis of BD with cerebral vasculitis was made and immunosuppressive therapy was started. Some improvement of the arterial lesions on MR angiography and normalization of CSF were observed after 1 year of treatment. DISCUSSION: Low grade chronic meningo encephalitis is the core neuropathological process in neuro-Behcet's disease. Nevertheless BD is a systemic disease known to cause vasculitis and can exceptionally lead to cerebral vasculitis and brain infarction. While BD is usually not part of the differential diagnosis of cerebral vasculitis, it should be borne in mind especially in endemic areas of the disease and in patients from these areas. PMID- 11784361 TI - A case with cerebral thrombosis receiving tamoxifen treatment. AB - Cerebral sinus thrombosis (CST) is known to be related to a number of underlying aetiologies including otitis media, trauma, pregnancy, birth control pills, tumours, malnutrition, dehydration, haematologic disorders and malignancy (Fishman, 2000; Raizer and Abbott, 2000). We present the case of a patient with breast cancer receiving the antioestrogen drug tamoxifen who developed CST. A 40 year-old female presented as an emergency with a 10-day history of headache and left sided weakness. On questioning her past medical history included a diagnosis of breast cancer 3 years ago treated by radical mastectomy and tamoxifen 20 mg daily. At the time of admission, neurologic examination revealed a mild left sided hemiparesis and a present Babinksi sign. Non-contrast enhanced tomography was normal. Magnetic resonance imaging (MRI) showed thrombosis in the superior sagittal sinus, right lateral sinus and jugular vein in addition venous infarction in the right temporal lobe was present (Figs 1a and b). Routine haematology and biochemistry was normal. Anticoagulation tests, antithrombin III, protein S and C levels were also found to be normal. She was treated with anticoagulation therapy and her hemiparesis improved within 3 days. Control MRI showed the resorption of the venous infarction and resolution of the thrombosis (Fig. 1c). PMID- 11784362 TI - Rapid clinical and CSF response to intravenous gamma globulin in acute disseminated encephalomyelitis. PMID- 11784363 TI - Effects on cognitive abilities following subthalamic nucleus stimulation in Parkinson's disease. PMID- 11784364 TI - Neutralizing and binding anti-interferon-beta antibodies. PMID- 11784365 TI - Meningioma of the conus medullaris: a common tumour in a rare localization and atypical clinical presentation. PMID- 11784366 TI - Vitamin B12 deficiency and dementia. PMID- 11784368 TI - Clinical application of transcranial colour-coded duplex sonography--a review. AB - Transcranial colour-coded duplex sonography (TCCS) is a new and non-invasive ultrasound application that combines both imaging of intracranial vessels and parenchymal structures at a high spatial resolution. This manuscript reviews the clinical applications of TCCS with focus on its diagnostic abilities in acute stroke patients. Furthermore, new experimental imaging techniques are discussed. PMID- 11784369 TI - The effect of stage of Parkinson's disease at the onset of levodopa therapy on development of motor complications. AB - The aim of this study was to ascertain whether the stage of Parkinson's disease (PD) (according to the Hoehn and Yahr staging system) would affect the length of time between the introduction of levodopa therapy and appearance of levodopa associated motor complications. Forty patients with clinically definite PD were studied. In all, clinical and therapeutic data were collected from the time of diagnosis to the time of levodopa-associated motor complications (i.e. dyskinesia, motor fluctuations). In 17 patients, levodopa could be started in Hoehn and Yahr stage I (H & Y-I; 16.2 months after the onset of PD), whilst in 13 patients levodopa could be started in H & Y-II (19.6 months after the onset of the disease) and in 10 in H & Y-III (45.1 months after the onset of PD). Cox proportional hazard regression model shows that the PD patients in whom the initial levodopa treatment was introduced at stage III develop both dyskinesias and motor fluctuations significantly earlier than the patients whose levodopa started in stage I and II of PD. The median interval to develop dyskinesias was 66, 72 and 24 months for patients in whom levodopa was introduced in stage I, II and III, respectively. These values were 64, 55 and 14 months for motor fluctuations. These findings add to the clinical arguments that favour an essential role of severity of PD at levodopa initiation as a risk factor for the development of levodopa-associated motor complications. PMID- 11784370 TI - A putative polymorphic Val44Ala variation in the synphilin-1 gene is undetectable in Japanese sporadic Parkinson's disease patients. AB - Recently, a novel protein-interaction partner of alpha-synuclein, designated synphilin-1, is identified as a constituent of Lewy bodies (LB) in Parkinson's disease (PD) brains. To investigate an involvement of genetic variations of synphilin-1 in development of sporadic PD, a possible single nucleotide polymorphism (SNP) of T131C corresponding to a valine (Val) to alanine (Ala) substitution at codon 44 in exon 3 of the synphilin-1 gene was studied in a Japanese population of 55 patients with sporadic PD and 61 patients with non-PD by direct sequencing analysis. All 116 subjects showed a homozygosity of Val at codon 44 in the synphilin-1 gene, suggesting that this SNP is unlikely to affect genetic susceptibility to sporadic PD in the Japanese population. PMID- 11784371 TI - Dissection and atherosclerosis of carotid arteries in the young: role of the apolipoprotein E polymorphism. AB - Twenty-seven young (<50 years old) patients with spontaneous carotid artery dissection in 11 cases and carotid atherosclerosis in 16 cases were evaluated to determine the apolipoprotein E polymorphism. At the DNA analysis the epsilon3/epsilon3 genotype was observed in all patients with dissection, in 13 of 16 (81.2%) patients with atherosclerosis and in 27 of 30 (90%) controls. Three of 16 (18.8%) patients with atherosclerosis and 3 of 30 (10%) controls presented with the epsilon4/epsilon3 genotype, and this difference was not statistically significant. Moreover, observation of the epsilon4/epsilon3 genotype was not significantly higher in patients with atherosclerosis compared with those with dissection. No homozygote epsilon4/epsilon4, epsilon2/epsilon2 or heterozygote epsilon2 genotype was observed. No correlation was found between the presence of the epsilon4/epsilon3 genotype and vascular risk factors. Therefore, the epsilon4 allele seems to be involved in carotid premature atherosclerosis development whereas it may appear to be protective for artery dissection occurrence. A larger sample size is needed to support this suggestion. PMID- 11784372 TI - CADASIL syndrome in a large Turkish kindred caused by the R90C mutation in the Notch3 receptor. AB - Mutations in the Notch3 gene are the cause of the autosomal dominant disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The CADASIL is an adult-onset neurologic disorder (average age of onset is 45 years) characterized by recurrent strokes and dementia. Clinical features combined with cerebral magnetic resonance imaging (MRI), showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter, are highly contributive to the diagnosis. We present a Turkish family with CADASIL, in which 12 individuals in four generations were affected showing the typical clinical features of recurrent strokes. Mutation analysis of the Notch3 receptor gene identified the recently described R90C mutation in the N-terminal part of the gene in affected individuals. Interestingly, migraine without aura was found as an initial symptom of the disease in two young mutation carriers (22 and 25 years, respectively), who did not show any additional clinical features or any MRI abnormalities. This indicates that migraine without aura in the absence of MRI abnormalities may represent an early initial symptom of CADASIL, which is difficult to diagnose in the absence of molecular diagnosis. Therefore, the used molecular screening method for Notch3 mutations provides a rapid and accurate diagnostic tool in addition to the standard diagnostic procedures. PMID- 11784373 TI - Motor vehicle crashes and abnormal driving behaviours in patients with dementia in Mendoza, Argentina. AB - Studies conducted in industrialized countries have shown that elderly demented subjects have increased risk of car accidents. However, there is no information about the effect of dementia on driving habits in non-industrialized countries. The number of motor vehicle crashes (MVC) and abnormal driving behaviours (ADB) (e.g. not recognizing traffic lights, driving in the middle of the road, etc.) were assessed with a semi-structured interview in 56 demented subjects and 31 elderly controls, all of whom were active drivers, at the Regional Registry of Dementia in Mendoza. Detailed neurological, psychiatric and neuropsychological examinations were also conducted on each subject. The presence of dementia and sex (male) predicted ADB, MVC and number of MVC (two or more). Among demented patients, ADB and MVC were associated with sex (male) and number of MVC was associated with sex (male) and Blessed Dementia Rating Scale for activities of daily living scores. Neither ADB, MCV, or number of MVC were associated with education level, or with cognitive or psychiatric measures. These findings showed that in developing countries, dementia has a significant contribution to MVC and ADB, as occurs in industrialized nations. Consequently, legislation to curb the risk of accidents caused by demented patients should be implemented. Furthermore, physicians must encourage demented patients (or their families) to discontinue driving, even those with mild dementia syndrome. PMID- 11784374 TI - Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS. AB - We examined the effect of standard migraine prophylaxis with sodium valproate on repeated measures of occipital excitability using transcranial magnetic stimulation (TMS). We predicted that, comparing pre- and post-treatment assessments, a reduction in clinical migraine parameters would be paralleled by a decrease in excitability measurements.A total of 31 migraine patients enrolled in the study, for assessment prior to and 1 month after commencement of sodium valproate prophylaxis. At each assessment, we used a standardized protocol to stimulate the occipital cortex with a 90-mm circular (coil A) and 70 mm figure-of eight (coil B) coil. We recorded the threshold stimulation intensity at which subjects just perceived phosphenes. Subjects kept detailed records of headache parameters 1 month before and also during the study period. Valproate therapy significantly improved headache indexes, as expected. In MA subjects assessed with coil B, phosphene thresholds were significantly higher post-treatment than pre-treatment, but those for MO did not change. Modest correlations were observed in MA patients between increase in phosphene threshold and decrease in headache index. Although preliminary, the findings with coil B lend some support to the notion that effective migraine prophylaxis may be achieved through lowering cortical excitability by gamma-aminobutyric acid (GABA)-ergic intervention. Further investigation of the effect of sodium valproate or other similarly acting substances on cortical excitability in migraine is warranted. PMID- 11784375 TI - Spike-and-wave complexes and seizure exacerbation caused by carbamazepine. AB - The purpose of this research is to analyse patients in whom carbamazepine (CBZ) therapy adversely affected electroencephalogram (EEG) recordings leading to seizure exacerbation and to identify risk factors for these events. From a total number of 2191 patients (p.) included in the Municipal Epilepsy Center (MEC) database, 77 patients with spike-and-wave (SW) discharges while on CBZ treatment have been selected. Patient population was divided in two groups: (i) patients who were already receiving CBZ at the time of their first visit to the MEC; and (ii) patients to whom CBZ was prescribed during follow-up at the MEC. CBZ was discontinued in all patients with confirmed evidence of an increase in seizure frequency, or with no improvement of epilepsy. During follow-up, EEG findings as well as all clinical changes were duly recorded. Group 1: Carbamazepine was discontinued in 17 patients (p.) as a result of paradoxical reactions. This condition occurs when an antiepileptic drug (AED) appears to exacerbate a type of seizure against which it is usually effective, or when it leads to the onset of new types of seizures. Three p. were withdrawn because of inappropriate drug selection. Group 2: CBZ was discontinued in six patients (p.) as a result of paradoxical reactions. The paradoxical reaction was more frequent in patients with frontal epilepsy and generalized SW discharges on the EEG (P=0.09) and patients with benign rolandic epilepsy (BRE) with diffuse interictal sharp and slow-wave discharges. In both groups, clinical and electrical changes returned to their initial status upon CBZ withdrawal. On the basis of this study, it may be concluded that EEGs might eventually help to screen high-risk patients. If EEG recordings become substantially worse, with more frequent and longer generalized SW bursts after initiation of CBZ therapy, patients should be carefully monitored in order to detect any sign of clinical impairment. PMID- 11784376 TI - Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis. AB - Human CD137 (ILA/4-1BB), a member of the tumour necrosis factor (TNF) receptor family, regulates the activation and proliferation of immune cells, and may induce apoptosis (programmed cell death) of activated lymphocytes. A soluble form of CD137 (sCD137) released by activated lymphocytes may interfere with the activities of the membrane-bound CD137. This study reports the detection of significantly high intrathecal and systemic levels of sCD137 in patients with clinically active multiple sclerosis (MS) when compared with corresponding levels from patients with clinically stable MS or those with inflammatory and non inflammatory neurological disorders, or from healthy individuals. Intrathecal concentrations of sCD137 in patients with active MS correlate with the intrathecal release of the soluble death receptor protein Fas, but not with the release of interleukin-2, TNF or the synthesis of immunoglobulins G and M. Results presented here suggest that heightened release of sCD137 is a feature of clinically active MS. PMID- 11784378 TI - The epidemiology and treatment of Bell's palsy in the UK. AB - The study consisted of a survey of all new cases of Bell's palsy occurring between 1992 and 1996 in practices contributing data to the UK General Practice Research Database (GPRD). Data were extracted on age, sex, date of episode of Bell's palsy, household number, episodes of herpes simplex, treatment prescribed and referral to relevant hospital departments. A total of 2473 cases of Bell's palsy were identified. The overall incidence for the study period was 20.2 per 100 000 person years of follow-up (95% CI 19.4-21.0). Incidence increased with age. There was no difference in incidence according to sex or season but there were significant changes over time: incidence was higher in the first year of the study period than in subsequent years. There was no clustering of cases in households and no evidence of any tendency for herpes simplex infections to precede Bell's palsy. About 36% of cases were treated with oral steroids and 19% of episodes resulted in hospital referral. In conclusion, Bell's palsy is seen mainly in a primary care setting. The majority of cases are treated expectantly without drugs. Lack of household clustering and lack of a tendency of herpes simplex infections to precede Bell's palsy do not support a viral aetiology. PMID- 11784377 TI - Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. AB - Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late-onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma-like and others with early onset-like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non-acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non-thymectomized AChR antibody positive late-onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non-thymectomized cases showed an opposite trend. The three MG-related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late-onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies. PMID- 11784379 TI - Lower limb nerve impairment in diabetic patients: multiperspective assessment. AB - To assess the relationship between patient's perception of his own inferior limbs symptom and function and the clinical-neurophysiological assessment in patients affected by insulin-dependent diabetes mellitus (IDDM). We studied 50 consecutive outpatients affected by IDDM (23 men, 27 women). We used validated measurements clinical [Semmes-Weinstein (SW), vibration perception threshold (VPT), muscle strength, osteotendineous reflexes, etc.], neurophysiological (sural, peroneal nerves), metabolic and patient-oriented [North American Spine Society (NASS) questionnaire]. Patient-oriented scores were significantly related with neurophysiological findings of the inferior limbs. Our data suggest that electrodiagnostic tests are useful to assess the severity of the diabetic polyneuropathy not only because they provide a biological measurement of the nerve function but also because they appeared related to the patient's quality of life related to the peripheral nerve involvement. PMID- 11784380 TI - Maurice Ravel and right-hemisphere musical creativity: influence of disease on his last musical works? AB - The problem of finding correspondence between a particular neuronal organization and a specific function of the human brain remains a central question of neuroscience. It is sometimes thought that language and music are two sides of the same intellectual coin, but research on brain-damaged patients has shown that the loss of verbal functions (aphasia) is not necessarily accompanied by a loss of musical abilities (amusia). Amusia without aphasia has also been described. This double dissociation indicates functional autonomy in these mental processes. Yet verbal and musical impairments often occur together. The global picture that emerges from studies of music and its neural substrate is by no means clear and much depends on which subjects and which aspect of musical abilities are investigated. An illustration of these concepts is provided by the case of the French composer Maurice Ravel, who suffered from a progressive cerebral disease of uncertain aetiology, with prominent involvement of the left hemisphere. As a result, Ravel experienced aphasia and apraxia and became unable to compose. The available facts favour a clinical diagnosis of primary progressive aphasia (PPA), with the possibility of an overlap with corticobasal degeneration (CBD). In view of Ravel's clinical history, we propose that two of his final compositions, the Bolero and the Concerto for the Left Hand, include certain patterns characteristic of right-hemisphere musical abilities and may show the influence of disease on the creative process. PMID- 11784381 TI - Using simulated consultations to develop communications skills for neurology trainees. AB - Communication skills are essential for clinical medicine yet, unlike in general practice, trainees in specialist and general medicine are not formally trained in them. We have used videotaped recording of simulated consultations to evaluate their acceptability and usefulness for training neurology specialist registrars. Twelve specialist registrars in neurology participated; their perceptions of the method were assessed using quantified scales and focus groups. All but one of the 12 trainees found the exercise useful both for improving clinical skills and for the imparting of information. The median visual analogue scores (0=useless, 100=very useful) for history taking and for imparting information were 91 and 90%, respectively. The median scores [and interquartile range (IQR)] of perceived usefulness for communication skills increased before to after (for use of video) from 68 (58-78) to 88 (80-92)% (P < 0.02), and (for use of simulated patients) from 51 (40-71) to 86 (79-89)% (P < 0.02). The focus groups provided additional qualitative data supporting the technique. We conclude that videotaped consultations with simulated patients are valued by most neurology trainees, both for improving their history-taking skills and for imparting information. The technique could be used more widely in neurology training, and may have a role in assessment. PMID- 11784382 TI - Stroke in a scuba diver with patent foramen ovale. AB - Patent foramen ovale (PFO) is a frequent condition which carries a significant risk for stroke when associated with deep venous thrombosis and primary or secondary coagulation abnormalities. Here, we describe a patient in which scuba diving is thought to be associated with stroke in a subject with an otherwise clinically silent PFO. During a rapid ascent a 43-year-old-scuba diver reported weakness and paresthesias in the right arm which lasted about 10 min. He presented similar symptoms 2 days later 1 h after diving, and a third time on his flight back home. The MRI showed multiple hyperintense areas on T2-weighted images in the white matter. Transoesophageal echocardiography (TEE) showed a PFO, whilst all haematological and haemocoagulation tests were negative. Scuba diving may constitute a patho-physiological condition in the presence of PFO as breath holding promotes right-to-left shunt and arterialization of venous bubbles. PMID- 11784383 TI - Post-infectious central and peripheral nervous system diseases complicating Mycoplasma pneumoniae infection. Report of three cases and review of the literature. AB - Three patients with a central and peripheral nervous system disease complicating a Mycoplasma pneumoniae (M. pn.) infection are presented. Patient 1 suffered from bilateral optic neuritis as well as acute Guillain-Barre syndrome recovering after plasmapheresis. The two other patients suffered from severe haemorrhagic leukoencephalitis (Hurst) which only could be contained by aggressive decompressive craniectomy with duraplasty. All three illnesses were clearly shown to be associated with M. pn. infection. Our three patients represent the full scale of central nervous (CNS) (cerebral and myelitic) as well as peripheral nervous system (PNS) (GBS, optic neuritis) manifestation of a disease caused by the same pathogenetic - post-infectious - mechanism; pathogenic CNS and PNS epitopes might be shared in post-infectious neurological disease following M. pn. infection. PMID- 11784384 TI - Homozygous Machado-Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms. AB - A male patient carrying the homozygous gene for Machado-Joseph disease (MJD) presented at age 43 with sleep disturbances and psychiatric symptoms followed by ataxic speech and gait. A polysomnogram (PSG) showed decreased rates of sleep time and stage rapid eye movement (REM) and an increased rate of 'stage 1-REM with tonic EMG' (Tachibana et al., 1975); all compatible with REM sleep behaviour disorder (RBD). Molecular gene analysis at age 59 showed that the CAG repeat units in the MJD gene were 60 and 60, smaller than the reported lengths for homozygous MJD patients (63-70 and 66-72). In addition to sleep disturbances, in particular RBD, psychiatric symptoms may be important clinical features in both heterozygous and homozygous MJD. PMID- 11784385 TI - MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia--two cases. AB - Vitamin B12 deficiency causes haematological and neurological diseases. Subacute combined degeneration (SCD) of the spinal cord is characterized by degeneration of the posterior and lateral columns. We report two cases of SCD induced by nitrous oxide (N2O) anaesthesia. In both cases magnetic resonance imaging (MRI) of the spinal cord showed symmetric, reversible changes in the posterior columns, correlating well with patients' symptoms. PMID- 11784386 TI - A case of a rare association of spastic paraplegia and type III syndactyly. PMID- 11784387 TI - Small sensory fibre dysfunction in selective cholinergic dysautonomia. PMID- 11784388 TI - Topiramate in drug-resistant complex partial status epilepticus. PMID- 11784389 TI - Hyperactive gagging in multiple sclerosis. PMID- 11784390 TI - A patient with overlapping Bickerstaff's brainstem encephalitis, Miller Fisher syndrome and Guillain-Barre syndrome during the clinical course. PMID- 11784391 TI - Platitude theory or Picasso stroke. PMID- 11784393 TI - The effectiveness of music as an intervention for hospital patients: a systematic review. AB - INTRODUCTION: Over the past few decades there has been a growing interest in the use of music, which has seen it used to achieve a diverse range of outcomes. While music as an intervention for hospital patients has subject to considerable evaluation, many of these studies are small and findings are therefore often contradictory. This systematic review was conducted to investigate the effectiveness of music as an intervention for hospital patients. METHOD: A comprehensive search was undertaken involving all major health care databases. For studies to be included in the review they must have investigated the effect of music, involved adult hospital patients and used a randomized controlled trial design. These studies must also have used outcome measures such as anxiety, satisfaction, pain, mood and vital signs. Identified studies were critically appraised, and then categorized according to whether music was evaluated during normal care delivery or during invasive and unpleasant procedures. When appropriate, studies were combined in a meta-analysis. RESULTS: A total of 29 studies were identified that fulfilled the inclusion criteria, of which 10 were subsequently excluded following critical appraisal. Music played via headphones reduces anxiety of patients during normal care deliver, but it has no impact on the anxiety of patients undergoing procedures such as bronchoscopy, sigmoidoscopy or surgery with a spinal anaesthetic. Music produces a small reduction in respiratory rate during normal care delivery, but appears to have little effect on other vital sign parameters. It has no impact on the vital signs of patients undergoing procedures. Although the evidence is limited, music also appears improve the mood and tolerance of patients. CONCLUSION: This review demonstrates the effectiveness of music for the reduction of anxiety during normal care deliver. Given the inexpensive nature of this intervention, and the lack of adverse events, it is recommended as an adjunct to normal care practices. This review also highlights the need for further research into many aspect of this intervention. PMID- 11784394 TI - A review of older people's experiences with residential care placement. AB - BACKGROUND: Transition to the care and environment of a residential home has been identified in the literature as the most significant relocation affecting older people. However, little effort has been made systematically to review and synthesize the body of knowledge relating to older people's experiences with such placement. This has led to lack of concerted effort in the development of strategies to help elders adjust to such placement with dignity and success. AIM: This paper presents a critical review of the literature related to older people's experiences with residential care placement, with an attempt to identify how knowledge in this area could be moved forward. CONCLUSIONS: It is concluded that, while understanding of older people's pre and postplacement experiences was abundant, there was a dearth of literature on the actual experiences involved as older people made their day to day adjustment after placement. There is a need for future research to identify the dynamic processes of how older people come to terms with residential living. Future research should also focus on developing an accurate understanding of the adjustment experiences of elders with different ethnic background. PMID- 11784395 TI - Reliability and validity of the nutritional form for the elderly (NUFFE). AB - AIM: The aim of this study was to test the reliability and validity of the Nutritional Form for the Elderly (NUFFE). BACKGROUND: The prevalence of undernutrition among older people in nursing homes and hospitals reaches high levels. Assessment of older patients' nutritional status is an important task for nurses in clinical care. To use a simple nutritional assessment instrument for older people is one approach for nurses. Examples of such instruments are the well validated Mini Nutritional Assessment (MNA) and the newly developed NUFFE. METHODS: A total of 114 consecutively chosen, newly admitted older patients in an elder care rehabilitation ward in western Sweden were interviewed using the NUFFE and MNA. Arm and calf circumferences, body mass index (BMI), and presence of pressure sores and skin ulcers were noted as part of the MNA on admission. Weight was monitored and BMI calculated on discharge. Serum albumin levels on admission and discharge were used if these were available in the records. Reliability of the NUFFE was measured as homogeneity. Criterion related validity, concurrent validity, construct validity, and predictive validity were assessed with different statistical methods. The regional research ethics committee approved the study. RESULTS: The results showed that the NUFFE is a fairly reliable and valid instrument for identifying actual and potential undernutrition among older patients. CONCLUSION: The NUFFE is a simple tool for nurses to use to assess older patients with the aim of detecting undernourished individuals and those at risk for undernutrition. When doing a nutritional assessment with the NUFFE, the BMI ought also to be calculated. The assessment could also be combined with food intake recording for a period of time. PMID- 11784396 TI - Nurses and English primary care groups: their experiences and perceived influence on policy development. AB - AIMS OF THE STUDY: To investigate the experiences and perceived influence of nurses serving on English primary care group boards. BACKGROUND: The development of the nursing workforce and nursing services in primary care have been piecemeal and nurses have not always contributed to policy development. The recent establishment of primary care groups (PCGs) in the United Kingdom (UK) potentially offers nurses the opportunity to take a concerted and strategic role in developing professional roles and planning service developments. RESEARCH METHODS: As part of a longitudinal study of a 15% random sample of English primary care groups, nurse board members were surveyed in the winter of 1999. One hundred and forty-four nurses were invited to return self-completion questionnaires. RESULTS: Completed questionnaires were returned by 106 of those invited to participate (73%). Respondents reported that combining their usual work with their role in the PCG was frequently difficult. Only 26% perceived that they had been well prepared for their new role. Compared with other board members [for example, general practitioners (GPs)], nurses perceived that their own influence was limited, with only a quarter rating the influence of nurses on decision-making as great. Most of the sample were feeding back information to other primary care and community nurses working in the locality and 52% rated communication with this wider constituency as good or better. Nurse board members were enthusiastic about their role and optimistic about the positive future impact of PCGs on health. CONCLUSIONS: PCGs are still at a relatively early stage in their development. It is still too early to assess their impact on nurses working in primary care and community settings. Board membership offers nurses a voice in local health policy development. PMID- 11784397 TI - Professional and organizational obstacles to establishing a new specialist service in primary care: case study of an epilepsy specialist nurse. AB - BACKGROUND: Few evaluations of the effectiveness of specialist nurse-led services explore the nurse's experiences, attitudes and qualities. This can help us to understand why a service has the effects it does and to inform new specialist nurses of potential difficulties. AIM: To explore the experiences, feelings and perceived problems of providing a new specialist nurse service from the nurse's perspective. METHODS: This was a case study nested within a controlled trial that assessed the effectiveness of an epilepsy specialist nurse-led service on the quality of patient care. In-depth interviews were conducted with the specialist nurse at the end of the first and second year of the new service. Interviews were audio-tape recorded and transcribed verbatim. Transcribed text was methodically coded and themes were identified. A descriptive account, summarizing the findings of both interviews, was written based on the thematic coding of text. RESULTS: Overall, the epilepsy nurse felt a sense of achievement and believed that the service had had a beneficial impact on both patients and health care professionals in the locality. However, she experienced many operational problems, especially adapting to a primary care setting, difficulties in meeting practice staff and in motivating them, and contending with a heavy workload. These problems were partly attributable to her lack of community work experience and more generally to the structure of the service. CONCLUSIONS: Findings indicate that specialist nurses responsible for providing primary care services would benefit from having theoretical knowledge and practical experience of working in the community prior to starting in post. The aims of a service need to be consistent with the available resources. Accounts of other specialist nurse's experiences of providing a primary care service could help to reduce set up time. Finally, support in the form of a coherent team is important to avoid feelings of professional isolation and to maximize effective use of specialist skills. PMID- 11784398 TI - A study of skill mix issues in midwifery: a multimethod approach. AB - BACKGROUND: While skill mix studies are quite commonplace in health care, most have focused on the most effective use of staff and skill distribution in the field of nursing; few relate specifically to the midwifery profession. In Ireland there is no recognized midwifery assistant grade. AIMS: This paper describes a study that investigated the skill mix requirements of a midwifery service based in the Republic of Ireland. The project was built on previous research, which showed that due to undertaking a number of 'nonmidwifery duties', midwives were unable to undertake fully the work for which they were trained. RESEARCH METHODS: Data were collected using a variety of methods. These included postal questionnaires and the Delphi technique. The 'Delphi' was used to gain a level of consensus from hospital midwives (all grades) (n=194) and student midwives (n=79) on what are and what are not nonmidwifery duties. Analysis of secondary data (duty rotas and staff turnover data) was also undertaken. RESULTS: Findings indicate that the respondents spent a large proportion of their time undertaking clerical, domestic, portering and stock duties. They would welcome the introduction of midwifery assistants into the ward team and were able to identify those duties that such persons could undertake. CONCLUSIONS: Skill mix requirements and organizational strategies to deal with the workforce changes are highlighted. Due to the current shortage of midwives in many countries and the dearth of extant research in this area, the results and recommendations have implications for midwives nationally and internationally. PMID- 11784399 TI - The relationship between maternal needs and priorities in a neonatal intensive care environment. AB - AIM: The aim of this study was to investigate the nature and organization of maternal needs and priorities in a neonatal unit. BACKGROUND: The relationship between maternal needs and priorities appears to be an under studied area in neonatal nursing. METHODS: A quantitative survey was carried out based on 209 mothers with premature infants. Two self-assessment schedules were used: critical care maternal needs inventory (J. Leske, Heart and Lung 15, 27-42) and a ranking scale. The data were analysed with multivariate analysis. FINDINGS: Data analysis revealed clear priorities in maternal needs. In particular the need for accurate infant related information was a priority for 93% of the mothers. Good communication practices with professionals were also valued. The mothers displayed altruistic behaviour, and self-related needs took second place. It is proposed that maternal needs demonstrate a hierarchical organization. CONCLUSION: It is important for nurses to consider the individual needs of the mothers, simply because the satisfaction of these needs is essential for maternal well being. PMID- 11784400 TI - The role of the nurse within the multi-professional rehabilitation team. AB - AIM OF THE STUDY/PAPER: To identify the contribution of the nurse within the multi-professional rehabilitation team. BACKGROUND: The requirement for nurses to work effectively within the multi-professional rehabilitation team is increasingly important with the higher incidence of chronic disease, growing numbers of older people and enhanced survival from major trauma. METHODS: A 2 year qualitative investigation was undertaken centred on three contrasting condition case studies (fractured neck of femur, rheumatoid arthritis and stroke). Clients were theoretically sampled, with their 'rehabilitation pathway' through different services providing the window through which the nurse's contribution was explored. Multiple methods and points of data collection were used, including observation, face to face interviews (clients, carers and staff) and record review. To enhance generalisability, a series of national expert workshops were undertaken with four groups: users, carers and carers' organizations; nurses; members of the multi-professional team; and educationalists. FINDINGS: Six interlinked roles for the nurse were identified: assessment, co-ordination and communication, technical and physical care, therapy integration and therapy carry-on, emotional support, and involving the family. Of particular significance is the creation of a supportive environment for rehabilitation to occur. Some nurses undertook aspects of all of these roles at any one time while others were only involved in one or two areas. While nurses expressed a desire to integrate therapy into their care delivery, the actual achievement of this goal was variable. CONCLUSIONS: Key elements of the nurse's contribution within rehabilitation should aim to maximize client choice to enhance independent living in the client's future environment. At a nursing educational policy level the nurse needs to have a full understanding of the principles and models of rehabilitation. At a practice level, the nurse's role must be valued and recognized, by nurses themselves and other team members. PMID- 11784401 TI - The personal and professional impact of undertaking an educational module on human caring. AB - AIM OF THE STUDY: To evaluate the personal and professional impact of undertaking a 15-week degree level module on nursing as human caring. BACKGROUND: Little is known about how to teach and enhance caring practices. An innovative module was implemented on a 4-year, postregistration nursing degree course in Wales to develop students' capacity to be caring practitioners. An understanding of its impact was sought to facilitate better future preparation of students. RESEARCH METHODS: A full cohort of 25 part-time students, divided into four groups, participated in audio-taped focus groups before and after undertaking the module. FINDINGS: From a personal perspective, the students experienced increased spiritual awareness characterized by: (1) enhanced connecting relationships with self and others, (2) finding purpose and meaning in life, and (3) clarification of values. Professionally, the module resulted in: (1) an increased knowledge and understanding of caring theory and related concepts, (2) a more holistic approach to care, and (3) enhanced caring practice. CONCLUSIONS: Education may enhance students' capacity to be caring practitioners. Spirituality, in particular, was illuminated for the students as an important means of developing both themselves and their caring practices. They experienced transformative learning, and the focus groups, employed as the research method, served as a useful vehicle in this process. Reflective groups will be used as a teaching method on future modules. PMID- 11784402 TI - The concept of self-management of type 1 diabetes in children and adolescents: an evolutionary concept analysis. AB - AIM: An evolutionary concept analysis was undertaken to clarify the concept of self-management of type 1 diabetes in children and adolescents. BACKGROUND: Several problems exist in the literature on self-management of type 1 diabetes in children and adolescents. There is no uniform terminology and there is no uniform definition of the concept. Also, there is no differentiation in the literature between self-management of diabetes in children and adults. METHODS: Ninety-nine references were reviewed and analysed in the disciplines of nursing, medicine, and psychology. After separate analyses revealed no significant differences across disciplines, the analyses were combined to describe the attributes, antecedents, consequences, and surrogate and related concepts. RESULTS: The three essential attributes of the concept were identified as process, activities, and goals. Self-management of type 1 diabetes in children and adolescents is an active and proactive process; it is daily, lifelong, and flexible, and it involves shifting and shared responsibility for diabetes care tasks and decision making between child and parent. It is a process that involves collaboration with health care providers. Self-management of type 1 diabetes in children and adolescents also consists of varied and many activities related to giving insulin, monitoring metabolic control, regulating diet and exercise, to name just a few. The concept also involves goals, which may differ from one parent/child dyad to another. A working definition of the concept is suggested. CONCLUSIONS: It is hoped that a more uniform definition of the concept will enable researchers to continue investigating antecedents and consequences of the concept in a way that allows for aggregating results. PMID- 11784403 TI - Children's rights: a decade of dispute. AB - AIM: This paper attempts to raise issues surrounding children's rights against a backdrop of ethical principles and their subsequent interpretation and application in practice. METHOD: Key words have been used to search a selection of electronic databases and a range of 'grey' literature has been reviewed. BACKGROUND: Over a decade ago the United Nations (1989) Convention on the Rights of the Child was ratified, with the exception of two member states (UNICEF 2000). The Human Rights Act (Department of Health 1998) became law in October 2000 in the United Kingdom (UK). Despite a decade of recommendations, guidelines and legislation, children's rights, particularly consent to health care, remain complex and inconsistent. As we move into a new era of human rights involving all members of society, it is timely for nurses in the UK to reflect on the challenges created in attempting to interpret the philosophy of such legislation because such complexity surrounds the interpretation of human rights for many other vulnerable clients within health care. FINDINGS: The interpretation of children's rights continues to be influenced by the evolution of the meanings of childhood. Adults view children's rights from multiple perspectives of best interest, which are determined by their beliefs about children's ability to understand and consent to health care and treatment. An ability and right to consent appears not to be balanced by the right to withhold consent. Inconsistency and ambiguity persist in the law and its interpretation. Adults need to develop a more pragmatic approach to children's rights. This requires better understanding of children and their experiences of health care. CONCLUSION: Until adults develop a more pragmatic ideology in relation to children's rights then a true respect for children's autonomy will not be achieved. Consent will therefore remain an adult and legal prerogative. PMID- 11784404 TI - Starry night: using story to inform aesthetic knowing in women's health nursing. AB - AIM OF THE PAPER: This paper describes the use of story as a vehicle to inform aesthetic knowing in nursing. Because health care demands that nurses know two distinct languages, the language of nursing science with its quantifiable outcomes as well as the experiential observations of health and illness, it is critical that nurses be fluent in each discourse. BACKGROUND: Nursing scholars have long voiced a commitment to two epistemological domains: scientifically derived knowledge (empirics) as well as the expressive, creative, intuitive application of knowledge (aesthetics). In recognition of the need for these interpretive paradigms for practice, nursing scholars have sought to identify the kinds of knowing which provide the nursing discipline with its unique perspective. DISCUSSION: Stories mould every human encounter and telling one's story in the context of a trusting relationship allows women and nurses to journey together to uncover and discover the meanings inherent in the story. Through this mutual process of unfolding the story, nurses engage the women in deep reflection and focus on what 'might be' so that possibilities for the future are illuminated. This is important in all nursing, but particularly in women's health nursing because the emergence of story suggests that contextual, phenomena centred knowledge has found its voice in the nursing care of women as a way of knowing that focuses on personal experience and relies on methods in which woman to-woman caring facilitates the disclosure of the human health-illness experience. CONCLUSIONS: Storytelling is a useful strategy to inform aesthetic knowing in nursing. Stories supply a foundation for nursing scholarship because truly to hear women's stories require nurses analyse information, formulate hypotheses, and seek to understand the causal relationships as expressed by women. Through this analysis and attention to detail, nurses are able to glimpse possibilities for the future, thus transforming the experience. PMID- 11784405 TI - Sponsorship of research in Public Health Nutrition. PMID- 11784406 TI - Serum carotenoids and radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project. AB - OBJECTIVE: Antioxidant intake has been associated with less progression of radiographic knee osteoarthritis (OA), but studies of carotenoid biomarkers and OA have not been done. We examined associations between serum concentrations of nine naturally occurring carotenoids and radiographic knee OA. DESIGN: The study design was matched case-control. Sera were analysed by high-performance liquid chromatography for nine carotenoids: lutein, zeaxanthin, alpha- and beta cryptoxanthin, trans- and cis-lycopene, alpha-carotene, and trans- and cis-beta carotene. Conditional logistic regression was used to estimate the association between tertiles of each carotenoid and radiographic knee OA, independent of body mass index, education, serum cholesterol, and the other carotenoids. SETTING: Johnston County, North Carolina, United States of America. SUBJECTS: Two-hundred cases with radiographic knee OA (Kellgren-Lawrence grades > or = 2) and 200 controls (Kellgren-Lawrence grade = 0) were randomly selected from the Johnston County Osteoarthritis Project, and were matched on age, gender and race. RESULTS: Participants with serum levels of lutein or beta-cryptoxanthin in the highest tertile were approximately 70% less likely to have knee OA than controls (odds ratio (OR) [95% confidence interval (CI)] = 0.28 [0.11, 0.73] and 0.36 [0.14, 0.95], respectively). Those in the highest tertile of trans-beta-carotene (OR = 6.40 [1.86, 22.1]) and zeaxanthin (OR = 3.06 [1.19, 7.85]) were more likely to have knee OA. CONCLUSIONS: While certain carotenoids may protect against knee OA, others may increase the odds of knee OA. Further study of carotenoids and knee OA are warranted before clinical recommendations about these substances and knee OA can be made. PMID- 11784407 TI - Dietary soy isoflavone intake in older Japanese American women. AB - OBJECTIVE: In a sample of older Japanese American women, we aimed to: (1) describe the most commonly consumed soy foods, (2) estimate dietary soy isoflavone intake, (3) describe characteristics associated with dietary soy isoflavone intake, and (4) compare our estimates with previously published estimates in other Japanese samples. DESIGN: A 14-item soy food-frequency questionnaire was administered to older Japanese American women and responses were converted to quantitative estimates of soy isoflavones (genistein plus daidzein). Multiple regression was used to examine characteristics associated with dietary soy isoflavone intake, including self-reported lifestyle and cultural factors and dietary intake of various foods ascertained from a semi quantitative food-frequency questionnaire. To compare our estimates with other samples, a review of the literature was conducted. SETTING/SUBJECTS: Data are from 274 women aged 65+ years, recruited from a longitudinal cohort study of Japanese Americans in King County, Washington State. RESULTS: The soy foods most commonly consumed were tofu (soybean curd), miso (fermented soybean paste) and aburaage (fried thin soybean curd). The mean intake of dietary soy isoflavones was 10.2 (standard deviation (SD), 12.4) mg day(-1), approximately a quarter to a half that of previously published estimates in Japanese samples. Dietary soy isoflavone intake was positively associated with speaking Japanese, the consumption of traditional Japanese dishes (kamaboko, manju and mochi), low fat/non-fat milk and yellow/red vegetables, vitamin E supplement use, and walking several blocks each day. Dietary soy isoflavone intake was negatively associated with the consumption of butter. CONCLUSIONS: The estimated dietary soy isoflavone intake in Japanese American women living in King County, Washington State was about a quarter to a half that of women living in Japan. Dietary soy isoflavone intake was associated with speaking Japanese and healthy lifestyle and dietary habits. PMID- 11784408 TI - Motivations for healthful dietary change. AB - OBJECTIVE: To describe scales that measure motivations for changing dietary behaviour, and to examine associations of these scales with current diet and dietary change. DESIGN: A secondary analysis of a randomised trial of a self-help intervention to promote lower fat and higher fruit and vegetable consumption. PARTICIPANTS AND SETTING: Participants were 1205 adults selected at random from enrolees of a large Health Maintenance Organization. At baseline, data were collected on motives for changing diet, fruit and vegetable intake, fat-related dietary habits, and demographic characteristics. Participants were then randomised to receive the intervention or to receive no materials. A follow-up survey was administered at 12 months. RESULTS: A majority of participants reported that it was very important to make dietary changes to feel better (72%) and to control an existing medical problem (57%), but very few (4%) were motivated by pressure from others. Factor analysis of the diet motivation items yielded two intrinsic ('self-image' and 'personal health') and one extrinsic ('social pressure') scales with fair internal consistency reliabilities (Cronbach's alpha = 0.59 to 0.68). Motivation scales were statistically significantly associated with demographic characteristics and baseline diet. For example, desire for a better self-image was a stronger motivator for changing diet among females, while personal health was more important to older persons and men (P < 0.001). Social pressure to change diet was statistically significantly associated with higher fat intake (r = 0.11) and self-image was associated with lower fat intake (r = -0.14, both P < 0.001). Motivation by social pressure and self-image were both significantly associated with greater fat reduction at 12 months post-intervention (P < 0.05). CONCLUSIONS: The intrinsic and extrinsic motivation scales were weakly associated with current diet and predicted response to dietary intervention. More research is needed to better characterise and measure motives for dietary change, and to test whether tailoring interventions based on individuals' motives for dietary change would improve intervention effectiveness. PMID- 11784409 TI - Comparison of a picture-sort food-frequency questionnaire with 24-hour dietary recalls in an elderly Utah population. AB - OBJECTIVE: To evaluate the 137-item Utah Picture-sort Food-frequency Questionnaire (FFQ) in the measurement of usual dietary intake in older adults. DESIGN: The picture-sort FFQ was administered at baseline and again one year later. Three seasonal 24-hour dietary recall interviews were collected during the year between the two FFQs. Mean nutrient intakes were compared between methods and between administrations of the FFQ. SETTING: The FFQ interviews were administered in respondents' homes or care-centres. The 24-hour diet recalls were conducted by telephone interview on random days of the week. SUBJECTS: Two hundred-and-eight men and women aged 55-84 years were recruited by random sample of controls from a case-control study of nutrition and bone health in Utah. RESULTS: After adjustment for total energy intake, median Spearman rank correlation coefficients between the two picture-sort FFQs were 0.69 for men aged < or = 69 years, 0.66 for men aged > 69 years; and 0.68 for women aged < or = 69 years, 0.67 for women aged > 69 years. Median correlation coefficients between methods were 0.50 for men < or = 69 years old, 0.52 for men > 69 years old; 0.55 for women < or = 69 years old, 0.46 for women > 69 years old. CONCLUSIONS: We report intake correlations between methods and administrations comparable to those reported in the literature for traditional paper-and-pencil FFQs and one other picture-sort method of FFQ. This dietary assessment method may improve ease and accuracy of response in this and other populations with low literacy levels, poor memory skill, impaired hearing, or poor vision. PMID- 11784410 TI - Reproducibility and validity of a quantitative food-frequency questionnaire among Jamaicans of African origin. AB - BACKGROUND: An interviewer-administered quantitative food-frequency questionnaire (FFQ) was developed to determine the energy and nutrient intakes of adult Jamaicans of African origin as part of a study of the epidemiology of diabetes and hypertension. METHODS: Reproducibility of the questionnaire was investigated in 123 participants aged 25-74 years. The relative validity of the FFQ was assessed against twelve 24-hour recalls administered over 12 months in 73 of the participants. In addition, energy intakes (EI) were compared with estimated basal metabolic rates (BMR). RESULTS: Reproducibility correlation coefficients (Pearson and intraclass) varied between 0.42 for retinol and 0.71 for carbohydrate, with most values falling between 0.50 and 0.60. When compared with repeated 24-hour recalls, the FFQ estimated slightly higher energy (mean 6%) and macronutrient intakes (mean 2-14%), and was within 5% when expressed as a percentage of energy intake. Micronutrients were higher by 1.19 (calcium) to 1.61 times (vitamin C). Unadjusted correlations between the FFQ and the reference method ranged from 0.20 for beta-carotene to 0.86 for alcohol. Cross-classification of nutrients into quartiles showed that 46-48% of participants in the lowest and highest quartiles were jointly classified by both methods. Misclassifications were low for most nutrients with one or two persons misclassified at the extreme quartiles. EI/BMR ratios suggested light to moderate activity levels appropriate for an urban population in a developing country. CONCLUSIONS: The FFQ showed reasonable reproducibility and validity and is suitable for estimating the habitual intakes of energy and macronutrients, but was poor for some micronutrients (retinol and beta-carotene). PMID- 11784411 TI - Estimation and validation of mercury intake associated with fish consumption in an EPIC cohort of Spain. AB - OBJECTIVE: To estimate mercury intake due to fish consumption among the individuals from Gipuzkoa participating in the European Prospective Investigation into Cancer (EPIC), and to validate the estimation of mercury exposure through diet, by measuring blood mercury level. DESIGN AND SETTING: The population for the EPIC Gipuzkoa cohort was recruited from 1992 to 1995. Each individual's diet was assessed regarding habitual intake over the previous year, using the diet history method. Blood samples were taken at the time of the interview. The mercury content of the fish species consumed was supplied by the Food Chemical Surveillance Programme in the Basque Country. SUBJECTS: For the estimation, 8417 volunteers, men and women, aged 35-65 years, of the EPIC cohort; for the validation, a random sample of 120 individuals stratified by fish intake was taken. RESULTS: The validation study confirmed the relationship between fish consumption and mercury intake, as well as between fish consumption and mercury in erythrocytes. 99.9% of individuals have intakes below 75% of the Provisional Tolerable Weekly Intake (PTWI) of mercury established by the World Health Organization. But the limit dosage recommended by the United States Environmental Protection Agency, measured by the average risk index, would be exceeded often. CONCLUSIONS: No individual from the cohort would exceed the PTWI of mercury. Nevertheless, owing to the amount of fish consumed, certain individuals would have mercury intakes approaching the recommended limits. With a view to the future, we believe mercury in fish must continue to be monitored closely in order to assess the risks for the population. PMID- 11784412 TI - Analysis of patterns of food intake in nutritional epidemiology: food classification in principal components analysis and the subsequent impact on estimates for endometrial cancer. AB - OBJECTIVE: To assess the effect of different methods of classifying food use on principal components analysis (PCA)-derived dietary patterns, and the subsequent impact on estimation of cancer risk associated with the different patterns. METHODS: Dietary data were obtained from 232 endometrial cancer cases and 639 controls (Western New York Diet Study) using a 190-item semi-quantitative food frequency questionnaire. Dietary patterns were generated using PCA and three methods of classifying food use: 168 single foods and beverages; 56 detailed food groups, foods and beverages; and 36 less-detailed groups and single food items. RESULTS: Classification method affected neither the number nor character of the patterns identified. However, total variance explained in food use increased as the detail included in the PCA decreased (approximately 8%, 168 items to approximately 17%, 36 items). Conversely, reduced detail in PCA tended to attenuate the odds ratio (OR) associated with the healthy patterns (OR 0.55, 95% confidence interval (CI) 0.35-0.84 and OR 0.77, 95% CI 0.49-1.20, 168 and 36 items, respectively) but not the high-fat patterns (OR 0.95, 95% CI 0.57-1.58 and OR 0.85, 0.51-1.40, 168 and 36 items, respectively). CONCLUSIONS: Greater detail in food-use information may be desirable in determination of dietary patterns for more precise estimates of disease risk. PMID- 11784413 TI - The development of food consumption in the Czech Republic after 1989. AB - OBJECTIVE: To define the average food consumption per capita in the Czech population and to investigate food consumption development during the years of economic transition. DESIGN: Three studies based on the household budget survey (HBS) were conducted in the 1990s. The primary data originated from so-called diaries of reporting households loaned out from the Czech Statistical Office (CSO). The arranging of representative samples has been done and is guaranteed by the CSO. Complementary inquiry was conducted to supplement the HBS data. The average consumption of basic food groups is presented. SETTING: All regions of the Czech Republic. SUBJECTS: The primary data came from the years 1991, 1994 and 1997. The basic sample representing the Czech population included 420 households and was arranged with regard to the region, size and socio-economic type of households. RESULTS: The changes in food consumption during the 1990s were reflected, above all, in meat, milk and dairy products, added fats, fruit and beverages. The consumption of poultry meat, fish, fresh fruit and vegetables has increased. The proportion of added fats has changed in favour of vegetable fats. On the other hand, a negative feature may be the permanent reduction in milk consumption. CONCLUSION: Most of the changes in eating patterns that appeared in the Czech population after 1989 can be interpreted as positive ones. PMID- 11784414 TI - Food habits of young Swedish and Norwegian vegetarians and omnivores. AB - OBJECTIVE: To determine the prevalence of vegetarianism and compare food habits among vegetarian and omnivorous adolescents in Sweden and Norway. DESIGN: Cross sectional study by questionnaire in Sweden and Norway to gather information about food habits. SETTING: The municipalities of Umea and Stockholm in Sweden, and Bergen in Norway. SUBJECTS: In total 2041 ninth-grade students (578 from Umea, 504 from Stockholm and 959 from Bergen), mean age 15.5 years, were included. The response rate was 95% in Umea, 91% in Stockholm and 83% in Bergen. RESULTS: There was a significantly higher prevalence of vegetarianism in Umea (15.6%) than in Stockholm (4.8%) and Bergen (3.8%). Vegetarians generally wanted more information about a healthy diet and vegetarian females ate dietary supplements to prevent deficiencies more often than omnivorous females (P < 0.01). The young male vegetarians more or less excluded animal products from their diet without changing their food frequency intake or modifying their dietary habits in other respects, while the young female vegetarians more often consumed vegetables and dietary supplements (P < 0.05). However, there was no difference between the intake of fruits/berries, alcoholic beverages, ice cream, sweets/chocolates and fast foods by vegetarians compared with omnivores. CONCLUSIONS: There were three to four times more vegetarians in Umea than in Stockholm and Bergen. The food habits of the young vegetarians differed from those of omnivorous adolescents and also in some respects from previously published comparative studies of vegetarians' and omnivores' food habits. It is uncertain whether the health benefits shown in previous studies on vegetarianism will be experienced by this young generation of vegetarians. PMID- 11784415 TI - Food company sponsorship of nutrition research and professional activities: a conflict of interest? PMID- 11784416 TI - Sponsorship of nutrition research in developing countries. PMID- 11784417 TI - Comparative clinical characteristics and responses to oral 4-aminoquinoline therapy of malarious children who did and did not develop 4-aminoquinoline induced pruritus. AB - The clinical characteristics and the responses to oral 4-aminoquinoline therapy of 150 malarious children presenting consecutively were investigated in an endemic area. At presentation, the 75 children who subsequently developed pruritus were significantly older and had significantly higher body temperatures than the 75 children who did not develop pruritus. There were no other significant differences in clinical presentation between the two groups. In children with pruritus, there was no correlation between age, weight, presenting body temperature, duration of illness or presenting peripheral parasite density and duration of pruritus. Responses to oral antimalarial drugs were similar in both groups. There was no correlation between indices of therapeutic response and the duration of pruritus. Analysis of the disposition kinetics of parasitaemia and of the hepatomegaly associated with malaria, using a non-compartmental model similar to that used in characterizing drug disposition, showed that the two groups had similar half-lives of parasitaemia (t(1/2 pd)), volumes of blood completely cleared of parasites per unit time (CL(Bpd)) and ratios of parasite clearance time to t(1/2 pd), and similar values for the corresponding parameters derived from hepatomegaly resolution. There was no apparent relationship between the indices of parasite- or hepatomegaly-disposition kinetics and the duration of pruritus. PMID- 11784418 TI - Plasmodium vivax relapses after 5 days of primaquine treatment, in some industrial complexes of India. AB - In an investigation of relapse patterns, 5541 cases of Plasmodium vivax malaria, from four major industrial complexes, each received at least one, 5-day course of primaquine (at 15 mg/day). Any subject relapsing was retreated with the same course. Overall, 511 (9.2%) of the P. vivax cases relapsed after the first course and 99 (1.78%), 25 (0.45) and three (0.05%) cases relapsed two, three and four times, respectively. Most cases of relapse occurred within 1 year of treatment. Clearly, a 5-day primaquine regimen is inadequate to control relapses among P. vivax cases and there is therefore an urgent need to review the treatment strategy. It may now be appropriate to implement the 14-day regimen recommended by the World Health Organization, although this is much less feasible under field conditions. PMID- 11784419 TI - Plasmodium falciparum in Kenya: high prevalence of drug-resistance-associated polymorphisms in hospital admissions with severe malaria in an epidemic area. AB - During an epidemic of Plasmodium falciparum malaria in Chogoria, Kenya, P. falciparum DNA was collected from 24 cases of severe malaria admitted to hospital for parenteral quinine treatment. These patients had all failed first- (chloroquine) and second-line (sulfadoxine-pyrimethamine or amodiaquine) drug treatments. Twenty-two (92%) of the 24 patients sampled carried parasites with the (Asn)86(Tyr) point mutation in the pfmdr1 gene (chromosome 5), 20 (83%) had an (Asp)1246(Tyr) mutation and 18 (82%) had both of these mutations. These alleles are both reported to be associated with chloroquine-resistance. Polymorphisms in the cg2 gene (chromosome 7) are also associated with chloroquine resistance, and 18 (75%) of the 24 parasite samples each had the cg2 and pfmdr1 polymorphisms. These 18 samples also had the mutations associated with resistance to pyrimethamine and sulfadoxine: (Asn)51(Ile), (Cys)59(Arg) and (Ser)108(Asn) of gene dhfr (chromosome 4) and (Ala)437(Gly) and (Lys)540(Glu) of dhps (chromosome 8), respectively. Genotyping of the parasites from all 24 patients revealed extensive diversity in the sequences for the merozoite surface antigens (MSA-1 and MSA-2) and the glutamate-rich protein (GLURP) and indicated that each sample contained more than one parasite clone. Although samples from non-admitted malaria cases were not available, it appears that drug resistance may have played an important role in the development of severe malaria in this epidemic. PMID- 11784420 TI - The performance and utility of rapid diagnostic assays for Plasmodium falciparum malaria in a field setting in the Lao People's Democratic Republic. AB - Rapid diagnostic assays for malaria have the potential to improve the management and control of the disease in developing countries. The objectives of the present study were to evaluate, in a field setting, the performance of several such assays for Plasmodium falciparum infection and to examine the usefulness of these assays in identifying subjects for treatment trials in rural field sites. Residents of 12 villages in Laos who presented with fever were eligible for inclusion. Blood was collected by fingerprick for a dipstick assay, developed by the Program for Appropriate Technology in Health (PATH), performed and interpreted in the field by local healthcare workers. Compared with 'blinded' reference microscopy (N =196), the sensitivity and specificity of the PATH assay were 96.2% and 93.0%, respectively. Two rapid diagnostic assays (PATH and OptiMAL) were also performed on the subset of subjects eligible to participate in an in-vivo treatment trial (N = 97), and the results again compared with those of 'blinded' reference microscopy. In this subset, a subject was considered a 'true positive' if found positive by microscopy or the alternate rapid assay. Using this modified reference standard, the sensitivity and specificity of the PATH assay were 96.7% and 94.4%, and those of the OptiMAL assay were 91.8% and 100%, respectively. Both of the rapid assays tested therefore appear suitable for use in rural field settings by local healthcare providers and can accurately identify participants for treatment trials. PMID- 11784421 TI - Human cystic echinococcosis: contributions to the natural history of the disease. AB - In areas where human cystic echinococcosis (CE) is endemic, the results of ultrasonographic or X-ray examinations have revealed a surprisingly high prevalence of abdominal cysts in asymptomatic individuals. The results of preliminary studies indicate that the ratio of liver infection:lung infection (LI:LU) is much higher in the asymptomatic individuals (9:1 or 7:1) than is usual among symptomatic cases of liver CE (2:1). This difference may indicate that, compared with lung cysts, liver cysts rarely cause morbidity, perhaps because they grow at a slower rate than those in the lungs. In an attempt to explore this possibility, the published results of ultrasonographic and radiological surveys on general populations and the records of autopsies and hospital-based investigations of symptomatic cases of liver CE were reviewed. In general populations, the overall prevalence of cysts in the liver (2.5%) was found to be much higher than that of cysts in the lungs (0.3%), giving a LI:LU ratio of 8.3:1. In the symptomatic cases, however, LI:LU ratios were only 2.5:1 (based on hospital records) or 4.1:1 (based on autopsy records). In addition, the estimated mean growth rate of the cysts in 53 surgical cases of CE from the province of Rio Negro in Argentina was found to be significantly higher than that of the cysts in 89 asymptomatic cases detected during ultrasonographic surveys in the same area. PMID- 11784422 TI - Risk factors for human alveolar echinococcosis: a case-control study in Hokkaido, Japan. AB - A case-control study to determine the risk factors for human alveolar echinococcosis (AE) was conducted in Hokkaido, Japan. The 134 cases were either patients clinically diagnosed as having AE (N =61) or other individuals found to be seropositive for Echinococcus multilocularis although showing no abnormalities in ultrasound scans (N = 73). Two groups of case-matched controls were employed: one of 670 individuals selected from a list of residents of Hokkaido (group A) and the other of 650 subjects selected from a list of individuals who had been found seronegative in earlier investigations (group B). Because of the long latency of AE, potential risk factors were studied over two different periods: for the 0-10 and 11-20 years before the year of diagnosis/recorded seropositivity. The results of multivariate analyses, in which the cases were compared with each control group, indicated that the rearing of cattle and pigs and the use of well water were significant risk factors and that the use of tap water significantly decreased the risk of an individual having AE. Extension of the piped water supply and health education on improving the disposal of household rubbish (to keep foxes away from houses) should help reduce the risk of AE infection in the study area. PMID- 11784423 TI - Urinary schistosomiasis in schoolchildren in Dar-es-Salaam, Tanzania, and the factors influencing its transmission. AB - The prevalence of urinary schistosomiasis among the schoolchildren living in Kigogo administrative ward of the Kinondoni district of Dar-es-Salaam city, Tanzania, and the factors influencing the transmission of the causative agent, Schistosoma haematobium, were investigated in a cross-sectional study. The estimate of overall prevalence, based on microscopical examination of a single urine sample/subject, was 47.6%. Compared with the girls, the boys were more likely to be excreting schistosome eggs (54.6% v. 40.8%; P = 0.004) and had, in general, higher intensities of infection (54 v. 38 eggs/10 ml urine; P = 0.001). The children aged 10-14 years had higher prevalences and intensities of infection than those in the younger or older age-group studied. The sensitivity of micro haematuria as an indicator of infection (compared with the microscopical examination of single urine samples) was 84.3% overall, reaching 92% among the children excreting > or = 50 eggs/10 ml urine. The corresponding positive and negative predictive values were 77% and 84%, respectively. The sensitivity, specificity and positive and negative predictive values of the history of haematuria as an indirect screening technique for S. haematobium were 60.4%, 72.7%, 67% and 67%, respectively. Recreational activities such as bathing, swimming and playing in the water were the most frequent activities attracting children to water bodies and carried the highest risks of infection with S. haematobium. Knowledge about the disease, especially on the symptoms and mode of transmission, was generally good but the methods of prevention were inadequately known. Chemotherapy to control urinary schistosomiasis in schoolchildren is recommended; infected children may be identified on the basis of haematuria, detected using questionnaires or reagent strips. Additional health education, to heighten awareness of the disease and its prevention, would also be beneficial. PMID- 11784424 TI - Determinants of hepato- and spleno-megaly in Hunan, China: cross-sectional survey data from areas endemic for schistosomiasis. AB - In order to understand the determinants of schistosome-related hepato- and spleno megaly better, 14,002 subjects aged 3-60 years (59% male; mean age = 32 years) were randomly selected from 43 villages, all in Hunan province, China, where schistosomiasis caused by Schistosoma japonicum is endemic. The abdomen of each subject was examined along the mid-sternal (MSL) and mid-clavicular lines, for evidence of current hepato- and/or spleno-megaly, and a questionnaire was used to collect information on the medical history of each individual. Current infections with S. japonicum were detected by stool examination. Almost all (99.8%) of the subjects were ethnically Han by descent and most (77%) were engaged in farming. Although schistosomiasis appeared common (42% of the subjects claiming to have had the disease), only 45% of the subjects said they had received anti schistosomiasis drugs. Overall, 1982 (14%) of the subjects had S. japonicum infections (as revealed by miracidium-hatching tests and/or Kato-Katz smears) when examined and 22% had palpable hepatomegaly (i.e. enlargement of at least 3 cm along the MSL), although only 2.5% had any form of detectable splenomegaly (i.e. a Hackett's grade of at least 1). Multiple logistic regression revealed that male subjects, fishermen, farmers, subjects aged > or = 25 years, subjects with a history of schistosomiasis, and subjects who had had bloody stools in the previous 2 weeks were all at relatively high risk of hepato- and/or spleno megaly. In areas moderately endemic for Schistosoma japonicum, occupational exposure and disease history appear to be good predictors of current disease status among older residents. These results reconfirm those reported earlier in the same region. PMID- 11784425 TI - Biological characteristics of praziquantel-resistant and -susceptible isolates of Schistosoma mansoni. AB - If there is a change in the biological characteristics of schistosomes associated with the development of resistance to praziquantel, this could affect the transmission and pathology of the diseases they cause. To investigate this possibility, the host-parasite relationships of five praziquantel-resistant and five praziquantel-susceptible isolates of Schistosoma mansoni were compared in Biomphalaria glabrata snails and outbred CD(1) albino mice. Whether praziquantel resistant or -susceptible, all the laboratory-selected isolates gave similar results in B. glabrata. However, the snails infected with any of three field collected isolates from Senegal, each of which has been shown to be praziquantel resistant, shed fewer cercariae and survived longer than the snails infected with the drug-susceptible or laboratory-selected, drug-resistant isolates. There were no differences between isolates in terms of their infectivity to mice. However, mice infected with any of four of the five drug-resistant isolates shed more eggs in their faeces than mice carrying the drug-susceptible parasites, and mice infected with any of the resistant isolates also had larger numbers of eggs in their tissues. Although granuloma sizes were generally similar for all isolates, the praziquantel-resistant isolates may be more pathogenic in mice than the susceptible ones because of their relatively high egg productions. PMID- 11784426 TI - Survival of heterophyid metacercariae in uncooked Thai fish dishes. PMID- 11784427 TI - Triatoma dimidiata Latreille, 1811 (Hemiptera: Reduviidae: Triatominae) in Central Mexico: first record for the state of Morelos. PMID- 11784429 TI - Malaria epidemiology and control in refugee camps and complex emergencies. AB - Owing to the breakdown of health systems, mass population displacements, and resettlement of vulnerable refugees in camps or locations prone to vector breeding, malaria is often a major health problem during war and the aftermath of war. During the initial acute phase of the emergency, before health services become properly established, mortality rates may rise to alarming levels. Establishing good case management and effective malaria prevention are important priorities for international agencies responsible for emergency health services. The operational strategies and control methods used in peacetime must be adapted to emergency conditions, and should be regularly re-assessed as social, political and epidemiological conditions evolve. During the last decade, research on malaria in refugee camps on the Pakistan-Afghanistan and Thailand-Burma borders has led to new methods and strategies for malaria prevention and case management, and these are now being taken up by international health agencies. This experience has shown that integration of research within control programmes is an efficient and dynamic mode of working that can lead to innovation and hopefully sustainable malaria control. United Nations' humanitarian and non-governmental agencies can play a significant part in resolving the outstanding research issues in malaria control. PMID- 11784430 TI - Modulation of host immunity by haematophagous arthropods. AB - The medical and veterinary public-health importance of haematophagous arthropods is immense and continuing to increase because of the emergence of new vector borne infectious agents and the resurgence of well known ones. Control of blood feeding arthropods and the pathogens they transmit is compounded by drug, insecticide and acaricide resistance. Novel control strategies are needed. Immunological control is one very promising approach to these problems. In order to develop anti-arthropod vaccines that block pathogen transmission and establishment, the immunological interactions occurring at the interface of the blood-feeding arthropod and host must be characterized. An important component of these interactions is arthropod modulation of the host's innate and acquired, specific immune defences. This review discusses current knowledge regarding the ability of haematophagous arthropods to alter their hosts' immune defences, the impact of those changes on pathogen transmission, the molecular bases for the immunomodulation, and strategies for identification of the molecules in arthropod saliva that are responsible for the immunomodulation. PMID- 11784431 TI - Therapeutic efficacy of chloroquine against uncomplicated, Plasmodium falciparum malaria in south-western Saudi Arabia. AB - The results of annual random screening indicated that Plasmodium falciparum strains showing chloroquine (CQ) resistance in vitro became increasingly common in the Jazan region of south-western Saudi Arabia between 1986 and 1998 (chi(2) for trend = 50.027; P < 0.001). This worrying trend and the emergence of a micro epidemic in 1997-1998 prompted an assessment of the therapeutic efficacy of CQ against uncomplicated, P. falciparum malaria in the area. The in-vivo testing of sensitivity to CQ was carried out in 291 clinically manifest, microscopically positive cases of P. falciparum malaria. Most of these patients (88%) were successfully treated with a single standard regimen of CQ therapy. The other 36 patients (12%) showed early treatment failure or a poor response to the CQ, although all of these were then successfully treated with a single standard dose of sulfadoxine-pyrimethamine (Fansidar), as a replacement therapy. Those unsuccessfully treated with CQ were generally younger (t = 2.625; P = 0.01) and tended to have higher body temperatures (t = -2.62; P = 0.012) and higher levels of parasitaemia at initial presentation (P > 0.000) than those who responded well to the drug. Although CQ remains a reasonably effective drug for the treatment of malaria in the Jazan region, and therefore will be kept as the first-line drug for the foreseeable future, failure of CQ efficacy must be carefully monitored in the area. PMID- 11784432 TI - Molecular markers for chloroquine-resistant Plasmodium falciparum malaria in Thailand and Laos. AB - Chloroquine-resistant Plasmodium falciparum is well documented in Thailand. Laos, however, continues to use chloroquine (CQ) as the first-line therapy for the treatment of P. falciparum malaria. The objective of the present study was to determine the prevalence, in these two areas, of the cg2, pfmdr1 and pfcrt allelic types that have previously been associated with CQ resistance. Isolates of P. falciparum were collected from participants in ongoing treatment studies conducted in Thailand (near the Thai-Cambodian border) and in Laos (Vang Vieng district). The pfmdr1 and pfcrt alleles were characterized by PCR-RFLP and mutations in cg2 were characterized by PCR and single-stranded-conformation polymorphism (SSCP) electrophoresis. Eight (32%) of the 25 Laotian isolates but only one (4%) of the 25 Thai isolates were found to contain the pfmdr1 mutation N86Y (P = 0.02). In contrast, the cg2 polymorphisms previously associated with CQ resistance were present in only 10 of the isolates from Laos but 24 of those from Thailand (40% v. 96%; P < 0.001). All the samples from both countries contained the pfcrt K76T mutant allele reported to confer resistance to CQ. The results may indicate that drug pressure for the maintenance of the pfmdr1 and cg2 alleles varies in intensity in the Thai and Laotian study areas, probably reflecting differences in the national malaria-treatment policies of Thailand and Laos. PMID- 11784433 TI - Malaria-attributable morbidity in Assam, north-eastern India. AB - Malaria is endemic in the Indian state of Assam and transmission of the causative parasites is perennial and persistent. The available data on malaria-related morbidity and mortality in the state for the years 1991-1999 have been reviewed. Over this period, Plasmodium falciparum was the predominant parasite, causing 58% 68% of the malaria cases; all other cases were attributed to P. vivax. All malaria-related deaths were attributed to P. falciparum infection, and the numbers of such deaths were correlated with the numbers of cases of P. falciparum malaria. The deaths occurred mostly in the rainy season (April-September) and among all age-groups of both sexes. The factors responsible for focal outbreaks of malaria across the state are discussed in relation to the existing health infrastructure. PMID- 11784434 TI - Trypanosoma brucei infection induces apoptosis and up-regulates neuroleukin expression in the cerebellum. AB - Human infection with Trypanosoma brucei may result in meningo-encephalitis, neuronal demyelination, blood-brain-barrier dysfunction, peri-vascular infiltration, astrocytosis and neuronal apoptosis. Prevention of the short- or long-term, parasite-induced, neuronal assault requires a better understanding of the host's responses to the infection at the molecular level. Northern analysis, cDNA micro-arrays, reverse-transcriptase-PCR (RT-PCR), SDS-PAGE and immunohistology were therefore used to investigate global gene and protein expression in the brains of mice infected with T. brucei. Temporal and spatial expression of neuroleukin (NLK), a predominant neurotrophin which is associated with neuronal protection and regeneration during neuronal assault in the brain, was then assessed. Expression of 20 of the 588 genes investigated (representing pro- and anti-inflammatory immuno-modulators, growth factors, neurotransmitters, and pro- and anti-apoptosis factors) was significantly altered (P < 0.05). TUNEL analysis revealed extensive apoptosis at peak parasitaemia, mainly in the cerebellum. RT-PCR analysis of two regulators of apoptosis, Bcl-x(L) (anti apoptotic) and Bax (pro-apoptotic), revealed equivalent increases in levels of expression. NLK expression was up-regulated in punctated fashion in brain and was mainly localized to abnormal (stellate) catecholamine neurons (CN) in the locus coeruleus (LC) of infected [and, to a lesser degree, the normal (polygonal) cells of uninfected] brainstem. Expression of NLK receptor (NLK-R) was inversely correlated with that of NLK. At peak parasitaemia, trypanosome infection apparently induces cerebellar apoptosis and a corresponding increase in NLK expression. NLK may be modulating inflammation and is probably involved in protecting CN and the cerebellum against apoptosis. PMID- 11784435 TI - Mixed leishmanial infections in Rhombomys opimus: a key to the persistence of Leishmania major from one transmission season to the next. AB - An important feature of the foci of zoonotic cutaneous leishmaniasis (ZCL) in Turkmenistan and Uzbekistan is a 6-10-month break in transmission when Leishmania parasites persist in great gerbils (Rhombomys opimus)--the main host for three species (L. major, L. turanica and L. gerbilli). Almost all (95%) of the laboratory-maintained R. opimus experimentally infected with L. major cured their infections within 6 months, a situation which, if mirrored in field conditions, cannot provide reliable persistence of the infection to the next transmission season. However, infections with L. turanica alone persisted for a mean of 15 months, and mixed infections of L. major and L. turanica persisted even longer (mean = 25 months), parasites of both species remaining detectable in the skin for at least 18 months. Isoenzyme identification of 664 isolates obtained from wild-caught R. opimus, and of 58 cloned strains developed from them, showed that L. turanica, which is non-pathogenic for humans, tends to predominate in the gerbils from all types of natural ZCL foci, including those which are hyper endemic; in June, L. turanica may be present in 80%-100% of the R. opimus in the foci. In contrast, infections with L. major alone occur far less commonly, and are especially hard to find at the beginning of the transmission season. However, 5%-25% of great gerbils in these foci are each infected with a mixture of L. major and L. turanica. In hyper- and meso-endemic foci, the proportion of L. major within mixed infections of Leishmania increases significantly towards the end of transmission season (August-September). It would appear, therefore, that mixed L. major/L. turanica infections in R. opimus promote the persistence of L. major between transmission seasons. PMID- 11784436 TI - Misidentification of Onchocerca volvulus as guinea worm. AB - Over the past 10 years, the status of human infection with guinea worm (Dracunculus medinensis) in the Central African Republic (CAR) has been difficult to ascertain. It is unclear if indigenous cases are occurring and whether cases are migrating into the CAR from surrounding countries. A team of investigators visited the CAR in July-August 2000, to attempt to ascertain the presence of indigenous transmission. No cases of true guinea-worm infection (i.e. dracunculiasis) were detected, but three cases of human infection with Onchocerca volvulus, each of which had been misidentified as dracunculiasis, were detected. The unusual presentation of skin blisters and extraction of an intact female O. volvulus are described. As a result of this investigation, and the confusion of onchocerciasis being misidentified as dracunculiasis, the presence of endemic transmission of guinea worm in the CAR remains in question. PMID- 11784437 TI - Subconjunctival zoonotic Onchocerca in an Albanian man. AB - A case of subconjunctival infection with a zoonotic species of Onchocerca is described, in a 16-year-old Albanian man who had immigrated to Greece. This is the first report of human infection with Onchocerca in this tissue location and only the eighth report of zoonotic Onchocerca in man. PMID- 11784438 TI - Evaluation of a PCR-ELISA to detect Wuchereria bancrofti in Culex pipiens from an Egyptian village with a low prevalence of filariasis. AB - The programmes for the elimination of bancroftian filariasis that have been implemented in the Nile delta of Egypt are expected to lead to substantial reductions in filarial loads in the treated populations. Better methods than those currently available are needed for monitoring the efficacy of these and similar efforts at intervention. A PCR-ELISA was therefore evaluated as an epidemiological tool for the detection of the Wuchereria-bancrofti-specific SspI repeat in pools of Culex pipiens collected in a village with a low prevalence of filarial infection in its human residents (2.1%). Indoor-resting mosquitoes were collected by aspiration from 114 randomly selected houses (during one to nine visits/house) and separated into 673 pools, each of which held the mosquitoes collected during one night from one house. Although 18 (2.7%) of the pools showed PCR inhibition and had to be excluded, filarial DNA was detected, using the PCR ELISA, in 91 (13.9%) of the 655 remaining mosquito pools. The minimum prevalence of W. bancrofti infection in the mosquitoes caught (assuming one infected mosquito/positive pool) was 2.8%. The mean (S.D.) number of mosquitoes/pool did not vary significantly between positive [5.5 (3.4)] and negative [4.9 (3.5)] pools. The assay detected parasite DNA in mosquitoes from 19.3% of 114 houses when only the first visit was considered and from 73.9% of the 88 houses visited more than once. The PCR-ELISA yielded results comparable with those of the regular PCR-SspI assay. The latter assay is recommended for the routine examination, in laboratories in endemic areas, of mosquito pools from randomly selected houses, as the ELISA component of the PCR-ELISA is exceedingly time consuming, expensive and requires special equipment. PMID- 11784439 TI - Cuticular-hydrocarbon discrimination between Anopheles gambiae s.s. and An. arabiensis larval karyotypes. AB - Examination of chromatograms of karyotyped larvae of Anopheles gambiae s.s. and Anopheles arabiensis has revealed that there are differences in the profile of their epicuticular hydrocarbons. A discriminant analysis of the quantitative hydrocarbon data has shown that the An. gambiae Mopti 2Rbc/bc karyotype from Mali could be separated from the Forest 2La/a karyotype from Liberia in > 80% of cases. Similar analysis permitted > 80% separation of individuals of two karyotypes of Anopheles arabiensis: 2Rab/ + from Burkina Faso, and 2Rb/b from Madagascar. PMID- 11784440 TI - A rapid-cooling method for cryopreserving Entamoeba histolytica. PMID- 11784442 TI - Neural interaction of the amygdala with the prefrontal and temporal cortices in the processing of facial expressions as revealed by fMRI. AB - Some involvement of the human amygdala in the processing of facial expressions has been investigated in neuroimaging studies, although the neural mechanisms underlying motivated or emotional behavior in response to facial stimuli are not yet fully understood. We investigated, using functional magnetic resonance imaging (fMRI) and healthy volunteers, how the amygdala interacts with other cortical regions while subjects are judging the sex of faces with negative, positive, or neutral emotion. The data were analyzed by a subtractive method, then, to clarify possible interaction among regions within the brain, several kinds of analysis (i.e., a correlation analysis, a psychophysiological interaction analysis and a structural equation modeling) were performed. Overall, significant activation was observed in the bilateral fusiform gyrus, medial temporal lobe, prefrontal cortex, and the right parietal lobe during the task. The results of subtraction between the conditions showed that the left amygdala, right orbitofrontal cortex, and temporal cortices were predominantly involved in the processing of the negative expressions. The right angular gyrus was involved in the processing of the positive expressions when the negative condition was subtracted from the positive condition. The correlation analysis showed that activity in the left amygdala positively correlated with activity in the left prefrontal cortex under the negative minus neutral subtraction condition. The psychophysiological interaction revealed that the neural responses in the left amygdala and the right prefrontal cortex underwent the condition-specific changes between the negative and positive face conditions. The right amygdaloid activity also had an interactive effect with activity in the right hippocampus and middle temporal gyrus. These results may suggest that the left and right amygdalae play a differential role in effective processing of facial expressions in collaboration with other cortical or subcortical regions, with the left being related with the bilateral prefrontal cortex, and the right with the right temporal lobe. PMID- 11784443 TI - Brain areas specific for attentional load in a motion-tracking task. AB - Although visual attention is known to modulate brain activity in the posterior parietal, prefrontal, and visual sensory areas, the unique roles of these areas in the control of attentional resources have remained unclear. Here, we report a dissociation in the response profiles of these areas. In a parametric functional magnetic resonance imaging (fMRI) study, subjects performed a covert motion tracking task, in which we manipulated "attentional load" by varying the number of tracked balls. While strong effects of attention--independent of attentional load--were widespread, robust linear increases of brain activity with number of balls tracked were seen primarily in the posterior parietal areas, including the intraparietal sulcus (IPS) and superior parietal lobule (SPL). Thus, variations in attentional load revealed different response profiles in sensory areas as compared to control areas. Our results suggest a general role for posterior parietal areas in the deployment of visual of attentional resources. PMID- 11784444 TI - When keeping in mind supports later bringing to mind: neural markers of phonological rehearsal predict subsequent remembering. AB - The ability to bring to mind a past experience depends on the cognitive and neural processes that are engaged during the experience and that support memory formation. A central and much debated question is whether the processes that underlie rote verbal rehearsal-that is, working memory mechanisms that keep information in mind-impact memory formation and subsequent remembering. The present study used event-related functional magnetic resonance imaging (fMRI) to explore the relation between working memory maintenance operations and long-term memory. Specifically, we investigated whether the magnitude of activation in neural regions supporting the on-line maintenance of verbal codes is predictive of subsequent memory for words that were rote-rehearsed during learning. Furthermore, during rote rehearsal, the extent of neural activation in regions associated with semantic retrieval was assessed to determine the role that incidental semantic elaboration may play in subsequent memory for rote-rehearsed items. Results revealed that (a) the magnitude of activation in neural regions previously associated with phonological rehearsal (left prefrontal, bilateral parietal, supplementary motor, and cerebellar regions) was correlated with subsequent memory, and (b) while rote rehearsal did not--on average--elicit activation in an anterior left prefrontal region associated with semantic retrieval, activation in this region was greater for trials that were subsequently better remembered. Contrary to the prevalent view that rote rehearsal does not impact learning, these data suggest that phonological maintenance mechanisms, in addition to semantic elaboration, support the encoding of an experience such that it can be later remembered. PMID- 11784445 TI - Posterior corpus callosum and interhemispheric transfer of somatosensory information: an fMRI and neuropsychological study of a partially callosotomized patient. AB - Interhemispheric somatosensory transfer was studied by functional magnetic resonance imaging (fMRI) and neuropsychological tests in a patient who underwent resection of the corpus callosum (CC) for drug-resistant epilepsy in two stages. The first resection involved the anterior half of the body of CC and the second, its posterior half and the splenium. For the fMRI study, the hand was stimulated with a rough sponge. The neuropsychological tests included: Tactile Naming Test (TNT), Same-Different Recognition Test (SDRT), and Tactile Finger Localization Test (intra- and intermanual tasks, TFLT). The patient was studied 1 week before and then 6 months and 1 year after the second surgery. Before this operation, unilateral tactile stimulation of either hand activated contralaterally the first (SI) and second (SII) somatosensory areas and the posterior parietal (PP) cortex, and SII and PP cortex ipsilaterally. All three tests were performed without errors. In both postoperative sessions, somatosensory activation was observed in contralateral SI, SII, and PP cortex, but not in ipsilateral SII and PP cortex. Performance was 100% correct in the TNT for the right hand, but below chance for the left; in the other tests, it was below chance except for TFLT in the intramanual task. This case provides the direct demonstration that activation of SII and PP cortex to stimulation of the ipsilateral hand and normal interhemispheric transfer of tactile information require the integrity of the posterior body of the CC. PMID- 11784446 TI - Implicit representations of space after bilateral parietal lobe damage. AB - There is substantial evidence that the primate cortex is grossly divided into two functional streams, an occipital-parietal-frontal pathway that processes "where" and an occipital-temporal-frontal pathway that processes "what" (Ungerleider and Mishkin, 1982). In humans, bilateral occipital-parietal damage results in severe spatial deficits and a neuropsychological disorder known as Balint's syndrome in which a single object can be perceived (simultanagnosia) but its location is unknown (Balint, 1995). The data reported here demonstrate that spatial information for visual features that cannot be explicitly located is represented normally below the level of spatial awareness even with large occipital-parietal lesions. They also demonstrate that parietal damage does not affect preattentive spatial coding of feature locations or complex spatial relationships between parts of a stimulus despite explicit spatial deficits and simultanagnosia. PMID- 11784447 TI - Hemispheric asymmetry in categorical versus coordinate visuospatial processing revealed by temporary cortical deactivation. AB - Kosslyn (1987) proposed that the left hemisphere is better than the right hemisphere at categorical visuospatial processing while the right hemisphere is better than the left hemisphere at coordinate visuospatial processing. In 134 patients, one hemisphere (and then usually the other) was temporarily deactivated by intracarotid injection of sodium amobarbital. After a hemisphere was deactivated, a cognitive test battery was conducted, which included categorical and coordinate visuospatial tasks. Using this technique, the processing capabilities of the intact hemisphere could be determined, thus directly testing Kosslyn's hypothesis regarding hemispheric specialization. Specifically, if the left hemisphere does preferentially process categorical visuospatial relationships, then its deactivation should result in more errors during categorical tasks than right hemisphere deactivation and vise versa for the right hemisphere regarding coordinate tasks. The pattern of results obtained in both categorical and coordinate tasks was consistent with Kosslyn's hypothesis when task difficulty was sufficiently high. However, when task difficulty was low, a left hemispheric processing advantage was found for both types of tasks indicating that: (1) the left hemisphere may be better at "easy" tasks regardless of the type of task and (2) the proposed hemispheric processing asymmetry may only become apparent during sufficiently demanding task conditions. These results may explain why some investigators have failed to find a significant hemispheric processing asymmetry in visuospatial categorical and coordinate tasks. PMID- 11784448 TI - Interference with performance of a response selection task that has no working memory component: an rTMS comparison of the dorsolateral prefrontal and medial frontal cortex. AB - It has been suggested that the dorsolateral prefrontal cortex (DLPFC) is involved in free selection (FS), the process by which subjects themselves decide what action to perform. Evidence for this proposal has been provided by imaging studies showing activation of the DLPFC when subjects randomly generate responses. However, these response selection tasks have a hidden working memory element and it has been widely reported that the DLPFC is activated when subjects perform tasks which involve working memory. The primary aim of this experiment was to establish if the DLPFC is genuinely involved in response selection. We used repetitive transcranial magnetic stimulation (rTMS) to investigate whether temporary interference of the DLPFC could disrupt performance of a response selection task that had no working memory component. Subjects performed tasks in which they made bimanual sequences of eight nonrepeating finger movements. In the FS task, subjects chose their movements at random while a computer monitor displayed these moves. This visual feedback obviated the need for subjects to maintain their previous moves "on-line." No selection was required for the two control tasks as responses were cued by the visual display. The attentional demands of the control tasks varied. In the high load (HL) version, subjects had to maintain their attention throughout the sequence, but this requirement was absent in the low load (LL) task. rTMS over the DLPFC slowed response times on the FS task and at the end of the sequence on the HL task, but had no effect on the LL task. rTMS over the medial frontal cortex (MFC) slowed response times on the FS task but had no effect on the HL task. This suggests that a response selection task without a working memory load will depend on the DLPFC and the MFC. The difference appears to be that the DLPFC is important when selecting between competing responses or when concentrating if there is a high attentional demand, but that the MFC is only important during the response selection task. PMID- 11784449 TI - Emotion and attention interaction studied through event-related potentials. AB - Several studies on hemodynamic brain activity indicate that emotional visual stimuli elicit greater activation than neutral stimuli in attention-related areas such as the anterior cingulate cortex (ACC) and the visual association cortex (VAC). In order to explore the temporo-spatial characteristics of the interaction between attention and emotion, two processes characterized by involving short and rapid phases, event-related potentials (ERPs) were measured in 29 subjects using a 60-electrode array and the LORETA source localization software. A cue/target paradigm was employed in order to investigate both expectancy-related and input processing-related attention. Four categories of stimuli were presented to subjects: positive arousing, negative arousing, relaxing, and neutral. Three attention-related components were finally analyzed: N280pre (from pretarget ERPs), P200post and P340post (both from posttarget ERPs). N280pre had a prefrontal focus (ACC and/or medial prefrontal cortex) and presented significantly lower amplitudes in response to cues announcing negative targets. This result suggests a greater capacity of nonaversive stimuli to generate expectancy-related attention. P200post and P340post were both elicited in the VAC, and showed their highest amplitudes in response to negative- and to positive arousing stimuli, respectively. The origin of P200post appears to be located dorsally with respect to the clear ventral-stream origin of P340post. The conjunction of temporal and spatial characteristics of P200post and P340post leads to the deduction that input processing-related attention associated with emotional visual stimulation involves an initial, rapid, and brief "early" attentional response oriented to rapid motor action, being more prominent towards negative stimulation. This is followed by a slower but longer "late" attentional response oriented to deeper processing, elicited to a greater extent by appetitive stimulation. PMID- 11784450 TI - The effects of frontal lobe lesions on goal achievement in the water jug task. AB - Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal. PMID- 11784451 TI - Non-response in alcohol and drug surveys: a research topic in need of further attention. PMID- 11784452 TI - Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals. AB - The causal relationship between cigarette smoking and cardiovascular disease (CVD) is well known and it is of great importance that smokers with CVD are encouraged to stop. Nicotine replacement therapy (NRT) is an effective aid to smoking cessation. However, its use in patients with CVD is often avoided because of warnings on product labelling. This is not justified, as NRT use in dependent smokers is much safer than smoking. Arguments are presented for the following guidelines which may be used when recommending NRT to patients with CVD; (i) NRT can normally be recommended to smokers with CVD who tried and failed to quit without such help; (ii) in patients who have experienced a serious cardiovascular event within the past 4 weeks, involve the patient's consulting physician. In less acute cases this is not needed; (iii) ensure dosing does not exceed the manufacturer's recommendation; (iv) warn patients to stop using NRT if they relapse to smoking; and (v) target motivated smokers (i.e. those seeking help), and where possible provide or arrange intensive behavioural support to accompany NRT. This advice is conservative, but will hopefully remove some obstacles faced by smoking cessation counsellors and other health professionals when considering the use of NRT in people with history of CVD. PMID- 11784453 TI - Conversation with Les Drew. AB - In this occasional series we record the views and personal experiences of people who have specially contributed to the evolution of ideas in the Journal's field of interest. Dr Drew is an Australian psychiatrist who has made substantial contributions to drug and alcohol policy development in his country. PMID- 11784454 TI - Naltrexone for alcohol dependence: a randomized controlled trial. AB - AIM: We examined the efficacy of naltrexone (an opioid antagonist) for alcohol dependence in a sample of alcohol-dependent men. DESIGN: A 12-week randomized placebo-controlled clinical trial. SETTING: The outpatient clinic of a combined war veteran and general teaching hospital in Melbourne, Australia. PARTICIPANTS: Male alcohol-dependent subjects recruited from the community and from veteran groups. INTERVENTION: Alcohol-dependent subjects were treated with 50 mg of naltrexone or placebo daily for 12 weeks. Both treatment groups attended a weekly education support group. Subjects were assessed weekly. MEASUREMENTS: Primary study outcomes were the maintenance of abstinence and relapse to drinking. FINDINGS: Fifty-five subjects were randomized to naltrexone and 56 to placebo. Forty subjects did not complete 12 weeks of therapy (17 naltrexone, 23 placebo). In the intention-to-treat sample (N = 111) fewer naltrexone treated subjects relapsed (p = 0.001). Among patients who completed the 12-week trial, naltrexone reduced the consumption of alcohol. Naltrexone was well tolerated and there were few adverse experiences. CONCLUSIONS: These findings demonstrate that naltrexone is effective in preventing relapse to drinking in the setting of limited psychosocial treatment. Further studies should examine the duration of treatment needed to maintain the effect long term. PMID- 11784455 TI - Episodic heavy drinking in four Nordic countries: a comparative survey. AB - AIMS: The purpose of this study was to compare the phenomenon of episodic heavy drinking (binge drinking) and its different indicators in the Nordic countries. DESIGN: A comparative survey of four Nordic countries. SETTING: Telephone interviews in Denmark, 1997; Finland, 1996; Norway, 1996; and Sweden 1996-97. PARTICIPANTS: Random samples of men and women aged 19-71 years. MEASUREMENTS: Episodic heavy drinking was measured by the frequency of subjective intoxication, of drinking six or more drinks at a time (6+), and of negative consequences (mainly hangover symptoms). Additionally, annual consumption and measures of intake per occasion were used. FINDINGS: Annual consumption, overall frequency of drinking and frequency of drinking 6+ were highest in Denmark and lowest in Norway. Frequency of subjectively defined intoxication was highest in Finland. There it was clearly higher than the frequency of drinking 6+, whereas in Denmark the contrary was observed. Finnish and Norwegian men and Danish women reported the largest quantities drunk per occasion. Results on 6+ frequency and the prevalence of negative consequences, with annual consumption held constant, suggest that Danes have the least concentrated drinking pattern. With annual consumption held constant, Norwegians report as high a frequency of intoxication, as do Finns. CONCLUSIONS: The relations between subjective and more objective measures of episodic heavy drinking vary considerably between the Nordic countries. The results suggest that the definition, acceptability and experience of intoxication vary even when a set of relatively homogeneous countries are compared. PMID- 11784456 TI - Alcohol use, drug use and alcohol-related problems among men who have sex with men: the Urban Men's Health Study. AB - AIMS: To measure the prevalence and independent associations of heavy and problematic use of alcohol and recreational drugs among a household-based sample of urban MSM (men who have sex with men). DESIGN: Cross-sectional survey. PARTICIPANTS: Men who identified as being gay or bisexual or who reported sex with another man in the prior 5 years were included in this analysis (n = 2172). SETTING: A probability telephone sample of MSM was taken within Zip Codes of four large American cities (Chicago, Los Angeles, New York and San Francisco) estimated to have total concentrations of at least 4% of all households with one resident MSM. MEASUREMENTS: Standard measures of alcohol use, problems associated with alcohol use, and recreational drug use were administered by trained telephone interviewers. FINDINGS: Both recreational drug (52%) and alcohol use (85%) were highly prevalent among urban MSM, while current levels of multiple drug use (18%), three or more alcohol-related problems (12%), frequent drug use (19%) and heavy-frequent alcohol use (8%) were not uncommon. The associations of heavy and/or problematic substance use are complex, with independent multivariate associations found at the levels of demographics, adverse early life circumstances, current mental health status, social and sexual practices and connection to gay male culture. CONCLUSIONS: The complex pattern of associations with heavy and/or problematic substance use among urban MSM suggests that heavy and/or problematic substance use is grounded in multiple levels: the individual, the interpersonal and the socio-cultural. PMID- 11784457 TI - Alcohol, cannabis and tobacco use among Australians: a comparison of their associations with other drug use and use disorders, affective and anxiety disorders, and psychosis. AB - AIM: To compare relationships between alcohol, cannabis and tobacco and indicators of mental health problems in the general population. METHOD: A survey of a nationally representative sample of 10 641 Australian adults (the National Survey of Mental Health and Well-Being (NSMHWB)) provided data on alcohol, cannabis and tobacco use and mental health (DSM-IV anxiety disorders, affective disorders, other substance use disorders and screening positively for psychosis). FINDINGS: Alcohol showed a "J-shaped" relationship with DSM-IV affective and anxiety disorders: alcohol users had lower rates of these problems than non-users of alcohol, while those meeting criteria for alcohol dependence had the highest rates. Tobacco and cannabis use were both associated with increased rates of all mental health problems examined. However, after controlling for demographics, neuroticism and other drug use, cannabis was not associated with anxiety or affective disorders. Alcohol dependence and tobacco use remained associated with both of these indicators of mental health. All three types of drug use were associated with higher rates of other substance use problems, with cannabis having the strongest association. CONCLUSIONS: The use of alcohol, tobacco and cannabis are associated with different patterns of co-morbidity in the general population. PMID- 11784458 TI - IQ and personality traits assessed in childhood as predictors of drinking and smoking behaviour in middle-aged adults: a 24-year follow-up study. AB - AIMS: The identification of childhood personality predictors of drinking and smoking behaviour in adults. DESIGN: A 24-year follow-up study. SETTING: Prague, the Czech Republic. PARTICIPANTS: Combined cohorts of 220 males and females born of unwanted pregnancies, and 220 control subjects, examined with low attrition rates at ages 9-10, 21-23, 28-31 and 32-35. MEASUREMENTS: In childhood IQ was assessed by the Wechsler Intelligence Scale, Children (WISC), and personality characteristics were rated by teachers, mothers and classmates. In adulthood questionnaires and face-to-face interviews were used to assess drinking and smoking. FINDINGS: Unwanted pregnancy was not related to adult drinking and smoking. The ratings of childhood personality characteristics were condensed into three personality dimensions, i.e. conscientiousness, extroversion and neuroticism, interpreted as three of the Big Five personality dimensions, and found to show some stability into adulthood. Gender, IQ and the three childhood personality traits were used as predictors of adult drinking and smoking behaviour. Adult drinking behaviour was significantly predicted by the block of the three childhood personality traits, low conscientiousness predicting high drinking quantity per occasion (and heavy episodic drinking) whereas extroversion predicted subjects' average daily consumption. Smoking in adulthood was predicted by low IQ and low conscientiousness. CONCLUSIONS: IQ and personality traits in children explain to some degree the drinking and smoking behaviour of adult men and women, but the roles of the different components vary according to the form of substance use. PMID- 11784459 TI - Induced mood and persistence at gaming. AB - AIMS: Using the affect infusion model (AIM), this study aimed to assess the impact of prior mood on gaming persistence in regular and non-regular gamblers (assumed to be motivated and heuristic decision-makers, respectively). DESIGN, MEASURES AND SETTING: A 2 x 3 experimental design in a laboratory setting employed factors of gambler type (regular, non-regular) and prior mood (happy, neutral, depressed). Measures were number of trials played on a gambling game, and mood ratings (post-mood induction, during and after play). PARTICIPANTS AND INTERVENTIONS: Sixty regular and 60 non-regular gamblers (all male students) were assigned randomly to watch a video inducing one of the three mood conditions. They were then given AUD$10.00 to gamble in a computerized card-cutting game. FINDINGS: AIM predictions were supported: prior mood did not affect gaming persistence for regular gamblers, but non-regulars showed reduced persistence across happy, neutral and depressed moods. After-play mood ratings were related to winnings for regulars, and losing regulars were significantly more unhappy after-play compared to during-play, and compared to both their winning counterparts and non-regulars. Mood and winnings were unrelated for non-regulars, with little during- to after-play mood change. CONCLUSIONS: The findings speak to depression as a causal factor in addictive gambling. Depressed mood did not enhance persistence in regular gamblers, but rather failed to have the inhibitory effect observed in non-regular gamblers. Evidence of mood changes during gambling was obtained, although multiple measures (self-report, physiological indicators, anticipated states) of both affective valence and arousal are advocated for future studies. PMID- 11784460 TI - Gender differences in syringe exchange program use in Oslo, Norway. AB - AIMS: To examine gender differences in syringe exchange program (SEP) use, particularly frequent SEP use, within and across survey years. DESIGN: Three consecutive, anonymous cross-sectional surveys. SETTING: The SEP in Oslo, Norway. PARTICIPANTS: Two hundred and eighty-eight, 449 and 523 SEP participants interviewed during comparable 1-week periods in 1992, 1994 and 1997, respectively. MEASUREMENTS: Brief structured questionnaires assessed SEP use, HIV risk behaviors and self-reported HIV status. Chi square statistics, t-tests and analysis of variance were used to identify gender differences; logistic regression was used to identify independent correlates of frequent SEP use. FINDINGS: Women reported injecting more frequently than men, but neither reported more frequent SEP use nor acquiring more syringes during an exchange. Although syringe sharing decreased significantly over time, in 1997, 51% of SEP participants continued to share. HIV prevalence remained low (3-5%) over time. After controlling for gender, age and HIV risk factors, frequent SEP use was significantly correlated with frequent injection for both women (OR = 1.4) and men (OR = 1.5). A lack of income or benefits independently increased the likelihood of being a frequent SEP user (OR = 3.0), while having shared a syringe at last injection independently decreased this likelihood (OR = 0.5). CONCLUSIONS: Gender was not associated with frequent SEP use; rather, the single most important correlate of frequent SEP use was injection frequency. Women's need for sterile syringes may not be fully addressed, despite the existence of a well-established and well-utilized SEP. PMID- 11784461 TI - Is calculating pack-years retrospectively a valid method to estimate life-time tobacco smoking? A comparison between prospectively calculated pack-years and retrospectively calculated pack-years. AB - AIMS: To investigate the relative validity of retrospectively calculated pack years (py-retro) by comparing py-retro with prospectively calculated pack-years (py-pro). DESIGN: A 23-year ongoing cohort study (1977-2000). PARTICIPANTS: One hundred and fifty-four males and females, 13 years old in 1977 and 36 years old in 2000. SETTING: Amsterdam, the Netherlands. MEASUREMENTS: To calculate py-pro, current smoking and quitting efforts were investigated nine times in a period of 23 years with the help of an interview or a questionnaire. At the age of 36, subjects filled out a comprehensive questionnaire about their smoking history, to calculate py-retro. Individual differences between py-pro and py-retro were calculated. In addition, Cohen's kappa was calculated after categorising py-pro and py-retro into three groups. FINDINGS: (1) Py-retro does not under- or overestimate life-time tobacco smoking. (2) The relative validity of py-retro was moderate due to large individual differences between py-pro and py-retro. (3) The individual differences between py-pro and py-retro became larger, the higher the number of pack-years. (4) Mean difference (and 95% limits of agreement) between py-pro and py-retro was -0.039 (-5.23, 5.32) when average pack-years was < 5.2 and -1.17 (-10.00, 14.65) when pack-years > or = 5.2. 5. Cohen's kappa between categorized py-pro and py-retro was 0.79. CONCLUSIONS: Future researchers in the field of smoking should be aware of the moderate relative validity of py-retro. Categorizing py-retro into smoking groups results in a misclassification error that is smaller than the quantitative error in continuous py-retro, but goes together with a loss of information. PMID- 11784462 TI - Cannabis-induced Koro in Americans. AB - AIMS: Koro, an acute panic reaction related to the perception of penile retraction, was once considered limited to specific cultures. The disorder has appeared as part of a panic response to cannabis, but only in citizens of India. This study looked for cannabis-induced Koro in Americans. DESIGN: Given the relative rarity of cannabis-induced Koro, this work focused on individual case studies. PARTICIPANTS: Over 70 men responded by phone to report negative reactions to cannabis. Three of them (Caucasians aged 22-26 with years of experience with cannabis) spontaneously mentioned experiencing symptoms of Koro after smoking marijuana. FINDINGS: All three cases occurred after participants had heard about cannabis-induced Koro and used the drug in a novel setting or atypical way. Two of the men had body dysmorphia, which may have contributed to symptoms. All three decreased their cannabis consumption after the Koro experience. CONCLUSIONS: Koro, particularly cannabis-induced Koro, is not limited to Eastern cultures. Several factors may interact to create symptoms. These include previous knowledge of cannabis-induced Koro, the use of marijuana in a way that might heighten a panic reaction, and poor body image. In addition, these cases confirm previous work that shows that negative reactions to drugs can attenuate their use. PMID- 11784463 TI - Can one tell a book by its cover? PMID- 11784464 TI - Have the courts and the motor vehicle departments adequate power to control the hard-core drunk driver? PMID- 11784465 TI - Conversation with Frederick B. Glaser. PMID- 11784466 TI - The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review. AB - AIMS: To examine the effectiveness of brief behavioral interventions adapting the principles and techniques of Motivational Interviewing (MI) to four behavioral domains: substance abuse, smoking, HIV risk and diet/exercise. DESIGN: We conducted a systematic review of 29 randomized trials of MI interventions. Data on methodological quality were extracted and tabulated. Between-group behavior change effect sizes and confidence intervals were calculated for each study. FINDINGS: Due to varying intervention time lengths, targeted problem behaviors, settings and interventionists' backgrounds and skill levels, outcomes were not combined meta-analytically. Sixty per cent of the 29 studies yielded at least one significant behavior change effect size. No significant association between length of follow-up time and magnitude of effect sizes was found across studies. There was substantial evidence that MI is an effective substance abuse intervention method when used by clinicians who are non-specialists in substance abuse treatment, particularly when enhancing entry to and engagement in more intensive substance abuse treatment treatment-as-usual. Data were inadequate to judge the effect of MI in the other domains. Client attribute-treatment interactions were understudied and the sparse and inconsistent findings revealed little about the mechanism by which MI works or for whom it works best. CONCLUSION: To determine more effectively how well MI works in domains other than substance abuse and for whom it works best in all domains, researchers should study MI with risk behaviors other than substance abuse, while examining both interactions and the theoretical components of MI. PMID- 11784467 TI - Exploring the relationship between alcohol consumption and non-fatal or fatal stroke: a systematic review. AB - OBJECTIVE: Alcohol consumption has been reported to have both beneficial and harmful effects on stroke occurrence. Several studies have demonstrated a significant association with heavy drinking, but the evidence linking light-to moderate alcohol consumption still remains unclear. This study, using a systematic review of the published literature, aimed to explore the dose-response relationship between alcohol and stroke, the effect of irregular drinking and the effect of beverage types on the risk of stroke. METHODS: A structured search for English-language published literature since 1966 was made using several electronic databases. This was supplemented using a hand search of references in review articles and additional searches on key authors. From the 153 eligible articles, 41 studies were selected according to study design, categorization of the exposure and outcome measures. FINDINGS: An association between recent alcohol use and stroke was consistently reported. There was also some evidence for a linear positive association for haemorrhagic stroke and alcohol consumption. Inconsistent results emerged on the J-shaped relationship between alcohol and ischaemic stroke, and the association between alcohol and non-fatal or fatal stroke combined. The importance of the pattern of drinking was also demonstrated, indicating a higher risk for irregular drinkers. CONCLUSIONS: There is insufficient evidence to conclude that light-to-moderate alcohol drinking and wine intake have beneficial effects on stroke occurrence. On the contrary, findings from this review suggest the opportunity for a primary prevention regarding heavy drinking and binge drinking. More information regarding the risk of stroke associated with irregular alcohol drinking, and the joint effects of alcohol with other risk factors, would clarify the complex interaction between alcohol and stroke. PMID- 11784468 TI - Regulation of nicotine replacement therapies (NRT): a critique of current practice. AB - Nicotine replacement therapy (NRT) describes a group of products delivering nicotine that are licensed for the relief of withdrawal as an aid to smoking cessation. This paper examines areas where public health considerations suggest changes should be made to the current indications and characteristics for NRT products. It is argued that the current regulatory framework restricts access to NRT without adequately considering that the likely consequence is continued dependent use of a far more harmful and widely available version of the same drug: tobacco. The paper argues that minors, pregnant smokers and smokers with cardiovascular disease (CVD) be allowed to use NRT. NRT use for smoking reduction, to support temporary abstinence, for long-term use should also be enabled and NRT products should be made as widely available as cigarettes. This paper also recommends that regulators encourage the development of less harmful forms of nicotine delivery devices to compete with cigarettes. Although this paper is written largely with reference to the UK medicines regulatory framework, these issues also apply to many other countries. PMID- 11784469 TI - Comments on Dunn et al.'s "The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review". Enthusiasm, quick fixes and premature controlled trials. PMID- 11784470 TI - A 10-year follow-up study on the health status of heroin addicts based on official registers. AB - AIMS: To determine the health status of a cohort of heroin addicts. DESIGN: Longitudinal follow-up study of a cohort for 10.5 years (March/July 1985-December 1995) based on official registers. SETTING: Catalonia, Spain. PARTICIPANTS: One hundred and thirty-five heroin addicts who started treatment in four specialized drug addiction services in Catalonia in 1985. MEASUREMENTS: (a) Total and annual numbers of AIDS and tuberculosis diagnoses and admissions to drug treatment; (b) annual morbidity rate; (c) average annual morbidity rate; and (d) standardized morbidity ratio. Kaplan-Meier (log rank test) was used to assess predictive factors. FINDINGS: During the follow-up period, 34 heroin addicts were diagnosed with AIDS (25%), the average annual morbidity rate was 2.7% and the standardized morbidity ratio was 82. The most frequent diseases indicative of AIDS were Pneumocystis carinii pneumonia (11 cases) and tuberculosis (seven cases of disseminated or extrapulmonary tuberculosis and two cases of pulmonary tuberculosis). Twenty addicts were diagnosed with tuberculosis and 15 were co infected with AIDS and tuberculosis. Seventy-six addicts were readmitted to treatment and generated 124 drug treatment episodes, 94 of whom were drug-free and 30 on methadone maintenance. CONCLUSIONS: Follow-up through registers is a novel, low-cost technique that may provide important and comparable information on the long-term evolution of drug addicts in different European regions. The measures of disease frequency and association obtained allow us to describe and compare the distribution of patterns of infectious complications (AIDS and tuberculosis) and relapses in such a pervasive disorder as heroin addiction. Other advantages of follow-up based on official registers are efficiency, reliability, sensibility and comparability. PMID- 11784471 TI - Predictors of hepatitis B and C infection in injecting drug users both in and out of drug treatment. AB - AIMS: To assess prevalence of, and behavioural risk factors for, hepatitis B and C in drug users both in and out of contact with drugs services. DESIGN: Cross sectional survey of hepatitis B and C prevalence using blood samples and self completed risk factor questionnaires. PARTICIPANTS: Three hundred and sixty injecting drug users (IDUs) in treatment for their drug use, attending syringe exchange schemes (SES), and not in contact with any services in Wirral and Manchester between 1997 and 1999, for whom test results were available for 334 (hepatitis B) and 341 (hepatitis C). FINDINGS: Hepatitis B prevalence differed between groups, from 19% of those not in contact to 41% of those presenting to request a test (p = 0.040). Prevalence of hepatitis C ranged from 48% (SES) to 62% among those presenting for a test (p = 0.233). After multivariate adjustment, hepatitis B was predicted by prison stays (p = 0.030) and injecting for longer (p = 0.003). For hepatitis C, length of injecting career (p = 0.036), having been to prison (p = 0.034), having injected more than one drug type (p < 0.001) and being female (p = 0.037) predicted infection. Overall, 38% had shared some form of injecting equipment in the previous 4 weeks. People recently starting injecting were more likely to share, and sharing was more likely to occur when injecting with only one other user rather than in larger groups. Those who had previously presented for a hepatitis C test, regardless of the result, were less likely to have recently shared injecting equipment. CONCLUSIONS: Behaviours associated with transmission of hepatitis B and C are common among IDUs. In particular, sharing of injecting equipment was more likely in small groups and in those recently beginning injecting. More broadly, chaotic drug use and time in prison were also risk factors for hepatitis infections. When assessing prevalence of hepatitis B and C, our results suggest that figures cannot be extrapolated from those in service contact to those in the wider drug-using population. PMID- 11784472 TI - Patterns of recent drug use among a sample of Australian detainees. AB - AIMS: To ascertain the prevalence of recent drug use among police detainees. Data. Data were gathered over a 1-year period in 1999 from detainees in four Australian police stations. Measures analysed include: (a) urinalysis results for cannabis, amphetamines, benzodiazepines, cocaine and opiates; (b) socio-economic and demographic backgrounds of detainees; and (c) arrest history and imprisonment. SETTING: Bankstown and Parramatta police stations, Sydney, East Perth Lockup, Perth and Southport Watchhouse, Southport, Australia. PARTICIPANTS: 1408 adult males detained by police were approached. Eighty-four per cent agreed to complete an interview and 70% provided a urine specimen. FINDINGS: Cannabis was most likely to be detected, followed by opiates, benzodiazepines, and then amphetamines. Very little cocaine was detected. Around three-quarters tested positive to at least one drug and around one-third tested positive to multiple drug use. Significant predictors for recent drug use were age, reported involvement in illegal activities and prior arrest and imprisonment. Those who tested positive to opiates were more likely to be charged with property offences while those who tested positive to cannabis were more likely to be charged with a drug offence. CONCLUSIONS: To monitor effectively patterns of drug use among at risk populations such as detainees data collections grounded at the local level are necessary. PMID- 11784473 TI - Overdoses among cocaine users in Brazil. AB - AIMS: A survey of cocaine users was undertaken to study (i) the frequency of reported drug overdoses among cocaine users; and (ii) the frequency of witnessing drug overdoses in the same population. DESIGN AND SETTING: A cross-sectional study as part of the World Health Organization (WHO) Multi-city Study among injecting drug users (IDUs), phase II, was conducted in Santos Metropolitan Region, State of Sao Paulo, Brazil, in 1999. PARTICIPANTS: Three hundred and ninety-six exclusive users of cocaine in the Santos Metropolitan Region, Sao Paulo State, Brazil were surveyed concerning their past experience with drug overdoses. FINDINGS: Eighty (20%) of the cocaine users reported having experienced one or more overdoses, and 50% reported that they knew one or more other cocaine users who had died of an overdose. On multivariate analysis, being female and having spent time in jail were associated with an increased likelihood of having had one or more overdoses. CONCLUSION: Cocaine overdoses are an important and under-recognized health problem in the Santos Metropolitan Region, and possibly in other areas of Brazil. PMID- 11784474 TI - Heroin use, ethnicity and the environment: the case of the London Bangladeshi community. AB - AIMS: To describe the emergence of heroin use in the London Bangladeshi community, to delineate its key features and generate hypotheses to account for these. DESIGN: Analysis of all reports of treatment-related episodes to a central data base. Detailed interviews with 21 Bangladeshi heroin users and a comparison group. SETTING: Treatment centres in three London boroughs with large Bangladeshi populations. FINDINGS: For young Bangladeshi men living in London, the prevalence of problematic heroin use has increased from negligible levels in the early 1990s to levels proportionally higher than in the white population of the same age and sex. The proportion of first episode reports has remained constant during this time. Bangladeshi heroin use has certain distinct features: users are nearly all male, and are apparently less disadvantaged than comparable white users. They also have much greater contact with their non-drug-using families. CONCLUSIONS: Because the population of Bangladeshis continues to grow, the epidemic may continue to grow in step with this. However, Bangladeshis may represent a group of heroin users with a good prognosis, and treatment services should, arguably, be aiming for better outcomes for them. Greater involvement of families may help to achieve this. PMID- 11784475 TI - Three decision-making tasks in cocaine-dependent patients: do they measure the same construct? AB - AIMS: Substance-abusing populations perform poorly on decision-making tasks related to delay and risk. These tasks include: (1) the Delay Discounting Procedure (DDP), in which choices are made between smaller-sooner and later larger rewards, (2) the Gambling Task (GT), in which choices are made between alternatives varying in pay-off and punishment, and (3) the Rogers Decision Making Task (RDMT) in which subjects choose between higher or lower probability gambles. We examine the interrelationship among these tasks. DESIGN: A test battery was created which included the DDP, GT and RDMT, as well as measures of impulsivity, intellectual functioning and drug use. SETTING: Subjects completed the test battery at an outpatient center, prior to beginning 12 weeks of treatment. PARTICIPANTS: Thirty-two treatment-seeking cocaine dependent individuals (primarily African-American males) participated. FINDINGS: Performance on the GT was significantly correlated with performance on the DDP (r = 0.37; p = 0.04). Reaction times on the RDMT correlated with performance on the GT (r = 0.36, p = 0.04) and DDP (r = 0.33, p = 0.07), but actual choices on the RDMT did not (p > 0.9 for both). While no significant relationships were observed between task performance and impulsivity, IQ estimate was positively correlated with both the GT (r = 0.44, p = 0.01) and RDMT (r = 0.41, p = 0.021). Split half reliability data indicated higher reliability when using only data from the latter half of the GT (r = 0.92 vs. r = 0.80). CONCLUSIONS: These data offer preliminary evidence of overlap in the decision-making functioning tapped by these tasks. Possible implications for drug-taking behavior are discussed. PMID- 11784476 TI - Lack of effects of ethanol pretreatment on the abuse liability of nitrous oxide in light and moderate drinkers. AB - AIMS: To determine effects of ethanol-use history and ethanol pretreatment on abuse liability of nitrous oxide (N(2)O). DESIGN: Placebo-controlled, double blind, cross-over design evaluating effects of N(2)O, 0% (100% O(2), placebo) and 30% (in O(2)), in the presence of three doses of ethanol: 0 g/kg (placebo), 0.35 g/kg and 0.7 g/kg. SETTING: Subjects sat in a reclining chair in a hospital laboratory. PARTICIPANTS: Eight healthy light drinkers (one drink or less/week) and eight healthy moderate drinkers (seven or more drinks/week) with no history of drug dependence completed the study. INTERVENTION: On three sessions (1, 3, 5) subjects drank a beverage that contained one of the three ethanol doses, then sampled for 10 minute each 0% and 30% N(2)O. During choice sessions (2, 4, 6), subjects received the same ethanol dose as in the previous session, then chose six times, once every 5 min, between 0% and 30% N(2)O. MEASUREMENTS: Subjective (self-reported) drug effects, reinforcing effects of N(2)O as assessed by choice, and psychomotor effects were measured. FINDINGS: Choice of N(2)O did not differ between light (mean = 3.4 choices) and moderate (mean = 3.2 choices) drinkers and was not influenced by ethanol dose (0 g/kg: 3.3 choices, 0.35 g/kg: 3.5 choices, 0.7 g/kg: 3.1 choices). Subjective effects of N(2)O also did not depend on ethanol-use history or ethanol dose. N(2)O liking and desire to inhale the drug again were positively correlated with N(2)O choice. CONCLUSIONS: Ethanol pretreatment and ethanol-use history had no effect on the abuse liability of N(2)O as assessed in the present study. PMID- 11784477 TI - Epidemiology of cigarette smoking in Pakistan. AB - AIMS: To study the prevalence of smoking among Pakistani population with particular reference to regional differences and correlates of cigarette smoking. DESIGN: Cross-sectional survey based on representative national sample. SETTING: Data collected through National Health Survey of Pakistan 1990-94. PARTICIPANTS: 13,104 individuals (6337 males and 6767 females), aged > or = 8 years. OUTCOME MEASURES: Prevalence and correlates of smoking. FINDINGS: Based on weighted estimates, the overall prevalence of cigarette smoking was 14.2% (95% CI: 13.6 14.8) in individuals aged > or = 8 years and 19.4% (95% CI: 19.08-19.72) among those aged > or = 15 years. The highest prevalence was seen in the province of Sindh (16.1%) and the lowest in North Western Frontier Province (7.1%). Nearly a quarter of males (25.4%) were smokers while only 3.5% of females smoked (p < 0.001). The smoking was slightly more prevalent in urban areas (15.2%) compared to rural areas (13.7%). This pattern was consistent in all provinces except the province of Sindh. The highest prevalence of cigarettes smoking among males (48.6%) was seen in those aged 25-44 years. After this age, there was a decline in smoking among males in Punjab and North Western Frontier Province, whereas the other two provinces, Sindh and Balochistan, did not show any such trend. CONCLUSION: Smoking is common in Pakistan. There is no clear policy on tobacco control in Pakistan. PMID- 11784478 TI - Naltrexone for alcohol dependence: comments on Morris et al. (2001). PMID- 11784479 TI - [Intravenous drug dependence: a public health problem in Spain]. PMID- 11784480 TI - [Mortality caused by cancer in Andalusia: trends and geographic distribution]. AB - AIMS: To describe the evolution of mortality due to gastric cancer in Andalusia and the current geographic distribution of mortality. DESIGN: Descriptive, population-based study. SETTING: Andalusia (Southern Spain) during the period from 1975 to 1999. PARTICIPANTS: Residents of the region of Andalusia. MEASUREMENTS: Crude rates adjusted for age (interval 35-64 years) of potential years of life lost (1-70 years), and cumulative rates (0-74 years), for mortality due to gastric cancer from 1975 to 1999. Linear regression coefficients were calculated from the model that best fit mortality rates standardized across the study period. Age-adjusted rates were calculated for the five-year period from 1995 to 1999 for primary health care districts. RESULTS: A sustained decrease in mortality (standardized rate per 100000 inhabitants) due to gastric cancer was seen in women (15.9 to 5.8) and men (33.9 to 14.5). The Sierra Norte (Seville province), Huelva and Cordoba districts, together with the Guadix district (Granada province), had the highest age-adjusted rates for the period from 1995 to 1999. Mortality rates were higher in men than in women throughout the period analyzed; the male:female ratio was consistently greater than 2. CONCLUSIONS: Mortality due to gastric cancer decreased notably in Andalusia during the last quarter of the twentieth century, but the current geographic distribution of mortality rates varies across the region. Mortality rates in some primary health care districts were threefold as high as in other districts where mortality was low. Further analytical studies are needed to clarify the possible causes of these marked local differences. PMID- 11784482 TI - [Effectiveness of cardiovascular prevention in primary care]. AB - OBJECTIVES: To evaluate the modification of risk factors and of coronary risk (CR) in adults (14-75 years old) after a period of 1 to 5 years in the PAPPS (special prevention programme). DESIGN: Multi-centre intervention study with no before-and-after random allocation. SETTING: Primary care. PARTICIPANTS: Patients included in the PAPPS at 3 health centres, 634 monitored for five years, 890 for four years, 1605 for 3 years and 2829 for 2 years, were evaluated.Interventions. Minimum counselling to give up tobacco and over-consumption of alcohol, and educational and pharmacological measures to reduce cholesterol and blood pressure. MAIN MEASUREMENTS: Recording of blood pressure, cholesterol, weight, and tobacco and alcohol consumption. CR was determined in the sub-group of 30-75 years old. These variables were determined at the start and end of the various monitoring periods. RESULTS: CR was reduced by between 0.2 and 0.3%; systolic blood pressure, by between 0.4 and 0.9 mmHg; diastolic pressure, by between 0.3 and 0.7 mmHg; cholesterol, by between 0.5 and 2.5 mg/dl; percentage of smokers, by between 0.3 and 2.8%; and over-consumption of alcohol, by between 0.2 and 1%. CONCLUSIONS: Scant success of the interventions to reduce CR and risk factors in the population as a whole. The main use of cardiovascular prevention programmes with many factors resides in detecting high-risk patients for subsequent intervention. PMID- 11784483 TI - [Prevalence of auricular fibrillation in people over 65 years of age in a health area]. AB - AIMS: To find the prevalence of auricular fibrillation in over-65s. DESIGN: Descriptive cross-sectional study through face-to-face interview and electrocardiogram. SETTING: La Solana Health District, Talavera de la Reina (Toledo). PARTICIPANTS: The entire population aged 65 or over (1206 people). Main measurements. Structured interview, study of patients clinical history, taking of blood pressure, and electrocardiogram with standardised measurement. RESULTS: 5.6% prevalence of auricular fibrillation. Distribution according to gender: 4.5% in men and 6.4% in women (p = 0.060; adjusted OR, 1.5). Prevalence of auricular fibrillation by age groups: from 65 to 74, 3.9%; from 75 to 84, 7.8%; over 85, 18.2% (p = 0.0001; adjusted OR, 2.14). CONCLUSIONS: There is greater prevalence of auricular fibrillation in the over 65s than in the general population. Prevalence increases with age. Gender has no statistical significance in the 65 to 74 age group, though it has in the over-85 group, in whom auricular fibrillation is more prevalent in women. PMID- 11784484 TI - [Analysis of the demand for a home care support team (HCST)]. AB - OBJECTIVES: To describe the clinical activity of the home care support team (HCST) over the first year of implementation in a health area. DESIGN: A descriptive, cross-sectional study. SETTING: Health Area 2 and 5 of Zaragoza (urban environment). PARTICIPANTS: All the patients (n = 151) included in the home care programme over the year 2000. MEASUREMENTS AND MAIN RESULTS: The mean age of attended patients was 77 years; sixty-three percent were woman. The most frequent medical disorders of the patients were neurologic (37.3%) and oncologic disorders (35%). The majority (88%) were referred from the primary care team (PCT). Subjects admitted from primary care of health (family physician or nurse) were 88%. The follow-up of these patients was carried out by the PCT (47.7%), mainly disabled patients, and 14% by HCST (significantly more frequent terminal ill patients). In 38.3% of the patients, follow-up was performed by both teams. Forty two percent of the patients attended died over the year 2000, 53% of them at home. CONCLUSIONS: Home care is an assistance model in progress. HCST are a resource that can become usefull in the development of the PCT work with all the hard to treat complex patients PMID- 11784485 TI - [The future of family medicine]. PMID- 11784486 TI - [Latest news on management of lower back pain]. PMID- 11784487 TI - [Motivation and family physicians (II)]. PMID- 11784488 TI - [Quality of the existing biomedical information on the Internet]. PMID- 11784489 TI - [Quality of life profile for the chronically ill (PECVEC): a method to evaluate well-being and functioning in clinical practice]. PMID- 11784490 TI - [Pulling the wool over our eyes]. PMID- 11784491 TI - [What underlies gonalgia in the general population?]. PMID- 11784492 TI - [Experience with anti-coagulation treatment at our health centre]. PMID- 11784493 TI - [Use of the subcutaneous route]. PMID- 11784494 TI - [Estimating the reliability of information obtained through questionnaires]. PMID- 11784497 TI - [Can specific verbal descriptors be useful in differentiating those with and without MI? Findings from a two-year study]. AB - This paper discusses the findings of a two-year study, which was based in an eleven-bedded coronary care unit in the South-West of England. The study aimed to explore the difference between the verbal descriptors used by those with and without MI in order to determine their contribution in assessing patients with a suspected MI. The study also examined whether any differences existed between the words men and women with MI used to describe their chest pain symptoms. All patients admitted with an episode of chest pain were eligible to participate providing that they were pain-free at 24 hours after admission, were over 18 years of age and could speak English. The sample comprised of 266 patients with MI and 275 without MI. All patients were offered a menu of 12 sensory and 10 effective words, which had been validated in previous research. The results suggest that there is little difference in the words patients with and without MI use to describe their chest pain and this may reinforce the complexity in obtaining an accurate differential diagnosis. However, there are some clear differences in the vocabulary of men and women with MI. Women with MI appeared to report more emotive language than men and expressed their chest pain in terms of being "frightened" (p < 0.05) and "terrified" (21.1 % vs 12.1 %). The discussion will examine the methodological issues and possible practice implications for the future. PMID- 11784498 TI - [Chest X-ray plate in bed-ridden patients in the Intensive Care Unit]. AB - Chest radiographs using portable equipment is one most frequently used radiological investigations for bed-ridden patients. As the investigation is carried out using ionising radiation, the protection measures to be applied should be known. These investigations are normally hindered by the patient's condition and it is important to take into account that this circumstance can cause differences in the radiological study. As in all radiological studies, the reading and the diagnosis should be systematic and it is necessary to recognise the different elements that these patients may bare, in addition to the symptomatology of the possible pathologies that may exist in the chest. PMID- 11784502 TI - [Temporary dependency of steroid-receptor prognostic value in breast cancer]. AB - BACKGROUND: The influence of prognostic factors in breast cancer may change during follow-up. Our aim was therefore to look for time-related changes in hazard ratios for steroid receptor status and the risk of relapse. PATIENTS AND METHOD: We studied 455 patients with operable primary breast cancer during a mean follow-up period of 72 months (range, 42-130 months). Clinical and histological characteristics were assessed and estrogen receptor (ER) and progesterone receptor (PgR) status were determined and compared to disease-free survival (DFS) and overall survival (OS). Analysis of DFS included fitting a multivariate Cox proportional hazards model, testing for non-proportionality, and examining diagnostic plots. RESULTS: A total of 66.8% of the tumors were ER positive and 54.7% PgR positive. Receptor status is highly associated with menopausal status, histological grade, peritumoral lymphatic or blood vessel invasion and mitotic index. No correlation was found between steroid receptor status and tumor size, node status or tumor stage. In univariate analysis, ER/PR vs ER+/PR+ display a hazard ratio of 2.15 (IC del 95%, 1.59-2.99) for DFS (p = 0.001) and 1.95 (IC del 95%, 1.38-2.59) for OS (p = 0.0043). In multivariate analysis, steroid receptor status, node status and mitotic index were independent prognostic factors for DFS and OS. By using Cox regression time-dependent covariates model, we show that the steroid receptor status hazard ratio is 5.6 at diagnosis, decreases after 4 years, and loses its significance after 10 years of follow-up. CONCLUSION: In patients with breast cancer the status steroid receptor have a relatively limited prognostic value and is lost within the first years. PMID- 11784503 TI - [Prevalence of malnutrition in the elderly Spanish population]. AB - BACKGROUND: Malnutrition in elderly has become an important problem of health, and is associated with an increase of morbidity and mortality in this age group. The aim of this study was to determine the prevalence of malnutrition in the Spanish institutionalized and living home elderly people. SUBJECTS AND METHOD: A sample of 3,460 representative Spanish subjects older than 65 years old were studied (response rate of 96%). Nutritional status was gathered by Mini Nutritional Assessment questionnaire. RESULTS: The prevalence of malnutrition was 3,3% among elderly living at home and 7,7% among institutionalized people. Malnutrition was more prevalent in women and people with a lower income. Increase of malnutrition with age was observed. CONCLUSIONS: The observed prevalence of malnutrition in Spanish non-institutionalized elderly people was similar to observed in another populations. Sex, age and income were associated with a risk of malnutrition PMID- 11784504 TI - [Review of infectious prophylaxis in splenectomized patients in the island of Menorca]. AB - BACKGROUND: Splenectomized patients are at higher risk of severe infection. PATIENTS AND METHOD: This retrospective study was performed to evaluate compliance with guidelines in patients who underwent a splenectomy between 1978 and 2000. Seventy-five patients were identified and their hospital records were reviewed. RESULTS: 62.7% of patients who had a splenectomy received a pneumococcal vaccine and were aware of the infectious risks related to an asplenic status. CONCLUSIONS: Rapidly lethal overwhelming sepsis in some asplenic patients demands greater prevention efforts by physicians. PMID- 11784505 TI - [Prognosis in dyspeptic patients under the age of 55]. AB - BACKGROUND: We studied the evolution and diagnostic tests performed in patients with dyspepsia aged less than 55 years. PATIENTS AND METHOD: We included 289 patients under age 55 with clinically manifest dyspepsia who were referred for specialized digestive evaluation from the primary care setting. RESULTS: One half of patients consulted again in the course of the study for the same symptoms. In 131 patients (45%), an endoscopy was proposed at some stage during the study. Gastroduodenal pathology was identified in 37% of the patients who underwent an endoscopy. CONCLUSIONS: In these patients, the approach adopted by the gastroenterologist must comprise assessment of the symptoms with endoscopy. PMID- 11784507 TI - [Prevention of fulminant sepsis in splenectomized patients: we keep forgetting health education]. PMID- 11784508 TI - [Stem cell gene therapy: myths an realities]. PMID- 11784509 TI - [Bioartificial liver support for acute liver failure. First case treated in Spain]. AB - BACKGROUND: Research aimed at developing artificial liver support systems has experienced a notable increase in the last decade. Hybrid systems including bioreactors containing hepatocytes which are perfused by liver failure patients blood or plasma have been deviced for the first time. The purpose of such a strategy is to substitute, at least in part, the impaired hepatic function thus improving the prognosis of patients with severe acute or chronic liver diseases. CASE REPORT: In the present paper, we report the first such a case treated in Spain in the context of a controlled, randomized, multicenter international study aimed at investigating the usefulness and safety of a bioartificial liver support system based on cryopreserved porcine hepatocytes in patients with acute liver failure or having a non-functioning primary graft after liver transplantation. RESULTS: In this first experience, two sessions of treatment could be completed before a patient with acute liver failure underwent a successful emergency liver transplantation. After more than two years of follow-up, the patient is in her normal life activities and she has not presented any adverse event related to the bioartificial liver support therapy so far. CONCLUSION: Bioartificial liver support systems are starting to be available for use in clinical practice. Yet it is mandatory to establish their safety and efficacy before a widespread recommendation. PMID- 11784510 TI - [Program for the Integral Care of the Physician (PAIME) of the Official Medical College of Barcelona]. PMID- 11784511 TI - [Health care response in disasters. Lessons learned from the terrorist attack against the Twin Towers of New York City]. PMID- 11784512 TI - [Should Helicobacter pylori infection be treated prior to long-term proton pump inhibitor therapy?]. PMID- 11784513 TI - [Conversion disorders: a therapeutic approach]. PMID- 11784514 TI - [Autoimmune lymphoproliferative syndrome]. PMID- 11784516 TI - [English edition of the Revista Espanola de Cardiologia on the Internet. A new big step forward]. PMID- 11784517 TI - [Natriuretic peptides in heart failure: improving diagnosis and management of the syndrome]. PMID- 11784518 TI - [Brain natriuretic peptide. Diagnostic value in heart failure]. AB - BACKGROUND: Nowadays a number of diverse biochemical markers have been identified in patients with heart failure (HF) that could indicate the severity of the patients' illness. Among them, probably the most useful is brain natriuretic peptide (BNP) because it is easily obtained and because of its diagnostic and prognostic information. Our objective was to assess the association between BNP and other different associated variables previously known to be related to the evolution of HF, as well as its utility to distinguish systolic from diastolic HF. PATIENTS AND METHOD: We studied 114 patients admitted consecutively for symptomatic HF for all causes (age: 66 years, male: 60%). In all patients plasma BNP was measured, from the third day of admission, with a specific radioinmunoassay. Echocardiography was performed in 101 patients. RESULTS: BNP plasma levels increased in proportion to functional class (p = 0.01) and the degree of left ventricular dysfunction (p = 0.0001, r = 0.44). There was also an association between BNP and male sex (p = 0.008), higher plasmatic creatinine (p = 0.01, r = 0.25), Iarger ventricular diameters (p = 0.0001) and higher pulmonary systolic pressure (p = 0.001, r = 0.44). In the multivariate analysis, BNP was independently related to the rest of variables with left systolic ventricular function (p = 0.0001). Despite this association, we did not find a satisfactory cut-off value in BNP, with a good sensitivity and specificity value from the total number of patients, of which specifically systolic dysfunction as a cause of HF was detected. CONCLUSIONS: a) BNP increases proportionately to the left ventricular dysfunction and HF severity, and b) BNP is not a useful tool to distinguish systolic from diastolic HF. PMID- 11784519 TI - [Implications of late expansion of self-expanding stents on neointimal response: a serial study with intravascular ultrasound]. AB - INTRODUCTION AND OBJECTIVES: A unique property of self-expanding stents is the continuous force exerted against the vessel wall, which may induce additional arterial damage with implications on restenosis. The main purpose of this study is to evaluate the consequences of late self-expansion of coronary Wallstents. METHODS: Eleven patients with Wallstents implanted in native coronary arteries, in whom baseline, post-stenting, after high pressure balloon inflation and at 6 month follow-up intravascular ultrasound were performed. The stented segments were divided in 2-mm cross-sections, that were analyzed independently and carefully matched at each situation using anatomic landmarks. Multiple regression analysis was performed. RESULTS: Late expansion was present in 93% of the studied sections (mean increase in stent area of 2.0 1.9 mm2) and was clearly related to stent oversizing (r = 0.45; p < 0,0001). Although late expansion was a significant positive predictor of neointimal growth (r = 0.63; p < 0.0001), it showed a negative correlation with late luminal loss (r = 0.33; p < 0.0001). No significant correlation was found between optimization of angiographic results with high pressure inflations and late luminal loss. CONCLUSIONS: Late expansion is a common phenomenon after Wallstent implantation and is mainly determined by stent oversizing. Despite the fact that this phenomenon is associated with greater neointimal proliferation, it seems to have a net beneficial effect on late luminal loss. PMID- 11784520 TI - [Percutaneous balloon pericardiotomy in patients with recurrent pericardial effusion]. AB - BACKGROUND: Recurrent symptomatic pericardial effusion can complicate different cardiac and extracardiac diseases. When recurrent pericardial effusion after drainage with conventional catheter techniques occurred the creation of a pericardial window by open surgery used to be the unique treatment available until the recent development of percutaneous balloon pericardiotomy. OBJECTIVE: The aim of this paper is to review our initial experience with percutaneous balloon pericardiotomy for the treatment of patients with recurrent pericardial effusion. PATIENTS AND METHOD: Five patients with recurrent pericardial effusion have been treated with percutaneous pericardiotomy until now. Four patients had malignant pericardial effusion secondary to metastasis of extracardiac tumors, in one patient recurrent pericardial effusion was idiopathic. In all patients percutaneous balloon pericardiotomy was performed with a pediatric valvuloplasty balloon catheter, through a subxiphoid approach. RESULTS: Successful drainage and balloon pericardiotomy was achieved in all patients without severe complications. In all cases only one pericardial site was dilated. Minor complications were registered, which included mainly mild pleural effusion occurring in all patients with spontaneous resolution. During a mean follow-up period of 8.6 6.5 months (range 2 to 18 months) there were no recurrences of effusion or tamponade. Two patients died, 1 month and 9 months after the procedure, due to their malignant condition. CONCLUSIONS: Percutaneous balloon pericardiotomy is an easy and useful technique to manage patients with large recurrent pericardial effusion with a low r PMID- 11784521 TI - [Multiplane transesophageal echocardiography in the preoperative evaluation of the sinus of Valsalva fistula to right chambers]. AB - INTRODUCTION AND OBJECTIVES: Ruptured sinus of Valsalva aneurysm to right cardiac chambers is an uncommon lesion in Western countries. The prognosis is usually serious unless the condition is promptly treated surgically. For this reason an accurate anatomical and functional evaluation is necessary. The main purpose of this report is to compare the usefulness of multiplane transesophageal echocardiography with transthoracic echocardiography and angiocardiography in the preoperative evaluation of ruptured sinus of Valsalva aneurysm to right chambers. PATIENTS AND METHOD: Since January 1990, 9 patients (mean age 36,3 18 yr, 6 males) with ruptured sinus of Valsalva aneurysm to right chambers were studied. The pathogenesis was congenital aneurysm in 6 patients, aortic prosthesis endocarditis in one and two cases of iatrogenia: during a percutaneous mitral valvuloplasty and after cardiac surgery. Transthoracic echocardiography was performed in all cases, transesophageal echocardiography in 7 and angiocardiography in 8. Two patients died before surgery, and 7 were successfully operated on. RESULTS: Transesophageal echocardiography was more useful when compared to transthoracic echocardiography and angiocardiography in detecting: a) the fistula; b) the sinus involved; c) the right chamber affected; d) congenital aneurysms morphology and size; e) aneurysm prolapse through a ventricular septal defect, y f) the identification of other cardiac congenital or acquired anomalies. CONCLUSIONS: Multiplane TEE is the most accurate tool in the preoperative evaluation of ruptured sinus of Valsalva aneurysm to right chambers. PMID- 11784522 TI - [Ablation of the cavotricuspid isthmus. Randomized prospective study of radiofrequency ablation with irrigated catheters versus standard catheters]. AB - INTRODUCTION AND OBJECTIVES: An important limitation of the ablation with standard catheter is the volume and limited depth of the lesions created. The irrigated catheters, due to a larger and deeper lesion could be useful in patients with typical atrial flutter. The aim of this study was to prospectively compare the ablation procedure with an irrigated-tip catheter versus the standard catheter in this group of patients. METHODS: A total of 37 consecutive patients referred to ablation of the cavotricuspid isthmus for typical atrial flutter were randomized either to be performed by an standard catheter (20 patients with mean age of 62 18 years, 18 males) or an irrigated-tip catheter (17 patients with mean age 71 4 years, 13 males). RESULTS: With standard catheters, complete ablation of the cavotricuspid isthmus was achieved in 18 patients (90%). With a mean of 19 15 applications. With the irrigated-tip catheters the complete ablation of the isthmus was achieved with a mean of 8 7 applications (p < 0.001). Both mean duration of the procedure (164 56 versus 70 35 minutes) and fluoroscopic time (40 16 versus 16 8 minutes) was significantly less with irrigated catheters (p < 0.001). There were no significant clinical complications during the procedure nor later on. No patient presented ischemic symptoms nor alterations on the ST segment. CONCLUSIONS: The employment of irrigated-tip catheters achieved a high success rate with safety shortening the procedure time and radiation exposure. PMID- 11784523 TI - [Electrophysiological and clinical characterization of left atrial macroreentrant tachycardia]. AB - BACKGROUND AND OBJECTIVE: We are reporting the characteristics of 9 patients with left atrial macroreentrant tachycardia, an arrhythmia not well studied in man. PATIENTS AND METHOD: Mean age was 60 years and 7 were men. Tachycardia was spontaneous in 6 and induced in 3. Two had no heart disease, 2 sick sinus syndrome, 3 aortic prosthesis, 2 hypertension, 1 cardiomyopathy and 1 chronic bronchitis. Simultaneous recordings from right atrial, coronary sinus and right pulmonary artery were obtained at baseline and with atrial pacing. Macroreentrant tachycardia was diagnosed when entrainment with fusion was documented. RESULTS: Cycle length was 230-440 ms (287 67). The ECG showed atypical flutter in 3 patients and P waves with flat baseline in 6. Coronary sinus activation was distal to proximal in 7. Right atrial activation was circular in 3 with previous typical flutter ablation. Entrainment from the right atrium produced long return cycles in the right atrial recordings, but equal to basal tachycardic cycle in coronary sinus recordings. Entrainment from the coronary sinus produced local return cycles equal to basal cycle in 8 and prolonged in 1. After stimulation, 4 recovered sinus rhythm, 4 went to atrial fibrillation and 1 had no change. After a follow-up of 9-19 months 5 remain in sinus rhythm treated with antiarrhythmic drugs and/or atrial pacing. CONCLUSIONS: Left atrial macroreentrant tachycardia is associated with organic heart disease. The ECG most frequent pattern tends to show P waves with flat baseline at a relatively slow rate. Most circuits turn clockwise in anterior view. Atrial stimulation is not very effective for cardioversion to sinus rhythm. The prognosis of long term rhythm is uncertain. PMID- 11784524 TI - [Changes in the clinical profile of patients treated with oral anticoagulants in the 1990's]. AB - INTRODUCTION: During the last few years the efficacy of oral anticoagulant treatment in the prevention of thromboembolic complications among patients with cardiac diseases has been well established. This has determined an increase in the number of patients undergoing this therapy and a change in the clinical profile of these patients. OBJECTIVE: To determine the number and the changes in the clinical characteristics of patients treated with oral anticoagulants during the last decade. PATIENTS AND METHOD: The charts of 5,771 hospitalized patients between January 1, 1991 and December 31, 1999, were retrospectively reviewed. We analyzed the number of patients discharged with anticoagulant treatment, the clinical profile and the evolution during the decade. RESULTS: 761 (13.1%) patients were discharged with anticoagulants. The therapy was prescribed to 7.4% of the patients from 1991-1993 and to 15.1% of the patients from 1998-1999. The mean age of the patients was 60.4 from 1991-1993 and 67.1 from 1998-1999 (p < 0.001). At the beginning of the decade, 90% of the patients had prosthetic valves, suffered from rheumatic heart disease or had had thromboembolic phenomena previously. At the end of the decade, only 49% could be included in these groups. CONCLUSIONS: a) The use of oral anticoagulants among our hospitalized patients has been duplicated during the past ten years; b) the clinical profile has changed, patients are now older and with different morbidity; c) the rheumatic heart disease and the prosthetic valves are no longer the predominant indications, and d) the use of therapy as secondary prevention has decreased significantly. PMID- 11784525 TI - [Importance of tumor necrosis factor-alpha in the pathogenesis of heart failure]. AB - Clinical and experimental evidence demonstrating the effects of tumor necrosis factor-alpha (TNF-alpha) in patients with heart failure continues to accumulate. It is well established that high concentrations of TNF-alpha appear in the circulation of patients with heart failure and that these levels have a directly proportional correlation with the patient's functional class. TNF-alpha levels also show a linear relation with prognosis. These circulating levels are responsible for the decreased expression of myocardial TNF-alpha receptors observed in heart failure. As a result of extrapolation of findings from experimental animals, we assume that TNF-alpha is deleterious to myocardial function in humans because it induces a negative inotropic state in patients who have not undergone heart transplant. Supporting this assumption is the fact that the resolution or improvement of pressure overload (obstructive hypertrophic myocardiopathy, by ethanol ablation) and volume overload (terminal dilated myocardiopathy, by ventricular assistance) states is accompanied by a decrease in myocardial TNF-alpha expression. The use of specific antagonists of circulating TNF-alpha in patients with symptomatic heart failure has been demonstrated to be safe and possibly effective. At present, multicenter studies are under way to assess the efficacy of this antagonism in a larger number of patients. If the results of these studies are favorable, we will have new therapeutic elements for managing patients with advanced hear failure. The transplanted heart behaves differently from the native heart. From the early stages of HTx, myocardial TNF alpha expression is greatly increased (much more than in patients with heart failure) and not associated with contractile dysfunction, in contrast with what occurs in the native heart. However, we know that the transplanted heart soon develops ventricular hypertrophy, fibrosis, diastolic dysfunction, and late graft failure, even in the presence of normal epicardial coronary arteries. Clinical evidence suggests that TNF-alpha may be involved in these processes. PMID- 11784526 TI - [Apical interventricular communication after lower infarction and anomalous origin of left coronary vessel]. PMID- 11784527 TI - [Stenting of right coronary artery arising from the left sinus of Valsalva]. AB - We report the stenting of a long lesion situated in an anomalous right dominant coronary artery arising from the left sinus of Valsalva. The patient was referred to our unit with a diagnosis of progressive angina and no other cardiopathy. We emphasize the convenience of having a good arrangement of the guiding-catheter with the original and the initial course of the artery, and also having a suitable support for the treatment programmed. PMID- 11784528 TI - [Isolated form of spongy myocardiopathy]. AB - Noncompaction of the ventricular myocardium sometimes referred to as spongy myocardium, is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. The characteristic echocardiographic findings of this disease consist of multiple myocardial trabeculations and deep intertrabecular recesses communicating with the left ventricular cavity. Familial occurrence has been observed. We present an illustrative case of isolated noncompaction of the ventricular myocardium in a 16-year-old patient, with the typical clinical and echocardiographic features of the disease. The literature on the topic is reviewed. PMID- 11784529 TI - [Survival after recurrent left ventricular free wall rupture, with an atypical occurrence after post-infarction exercise test]. AB - Left ventricular free wall rupture is an unusual but highly lethal complication of acute myocardial infarction. We report on the extremely rare occurrence of a patient surviving two episodes of free wall rupture within a seven-month period. The first event happened in the course of an exercise testing after a seemingly uncomplicated inferior acute myocardial infarction; the second, seven months after the first, as a pseudoaneurysm in the setting of a new inferior wall infarction. Surgical repair was successful in both instances, with patient remaining asymptomatic in follow-up. PMID- 11784530 TI - [Sinus of Valsalva aneurysm as a cause of acute myocardial infarction]. AB - Aneurysmal dilatation of one or more of the sinuses of Valsalva (SVA) is a rare cause of coronary insufficiency. We describe one case of unruptured and partially thrombosed right sinus of Valsalva aneurysm of which the first sign was acute inferior myocardial infarction in a 40-year-old man while reviewing the literature, we found 44 reported cases of sinus of Valsalva aneurysm, complicated by myocardial ischemia or infarction. In 28 cases the left coronary sinus was involved, in 12 cases the right one, and in 4 cases both of them. Myocardial ischemia is a potentially ominous prognostic sign in SVA patients. The poor outcome with conservative treatment leads us to consider the patient for emergency surgical therapy. PMID- 11784533 TI - Consequences of head size following trauma to the human head. AB - The objective of the present study was to evaluate whether variation of human head size results in different outcome regarding intracranial responses following a direct impact. Finite Element models representing different head sizes and with various element mesh densities were created. Frontal impacts towards padded surfaces as well as inertial loads were analyzed. The variation in intracranial stresses and intracranial pressures for different sizes of the geometry and for various element meshes were investigated. A significant correlation was found between experiment and simulation with regard to intracranial pressure characteristics. The maximal effective stresses in the brain increased more than a fourfold, from 3.6kPa for the smallest head size to 16.3kPa for the largest head size using the same acceleration impulse. When simulating a frontal impact towards a padding, the head injury criterion (HIC) value varies from the highest level of 2433 at a head mass of 2.34kg to the lowest level of 1376 at a head mass of 5.98kg, contradicting the increase in maximal intracranial stresses with head size. The conclusion is that the size dependence of the intracranial stresses associated with injury, is not predicted by the HIC. It is suggested that variations in head size should be considered when developing new head injury criteria. PMID- 11784534 TI - Mechanical properties in long bones of rat osteopetrotic mutations. AB - Osteopetrosis is a metabolic bone disease with increased skeletal density radiographically and increased risk of fracture. Experimental studies with rat osteopetrotic mutations have shown increased bone density and decreased bone strength. However, it is not known if this reduction in bone strength is only due to changes in structure and geometry or if the tissue properties of bone material itself are changed as well. We have evaluated bone tissue properties with nanoindentation in three osteopetrotic mutations in the rat (incisors-absent ia/ia, osteopetrosis op/op and toothless tl/tl) to test the hypothesis that reduced bone resorption in these mutations results in reduced tissue properties of bone material. No significant differences in elastic modulus or hardness were found between osteopetrotic mutants and their normal littermates (NLMs) in any of the three stocks. This indicates that the tissue properties of bone material are not changed significantly in osteopetrosis, even if the mechanical strength is decreased at the macroscopic level. PMID- 11784535 TI - A contact model with ingrowth control for bone remodelling around cementless stems. AB - This work presents a computational model for bone remodelling around cementless stems. The problem is formulated as a material optimisation problem considering the bone and stem surfaces to be in contact. To emphasise the behaviour of the bone/stem interface, the computer model detects the existence of bone ingrowth during the remodelling; consequently, the contact conditions are changed for a better interface simulation. The trabecular bone is modelled as a strictly orthotropic material with equivalent properties computed by homogenisation. The distribution of bone relative density is obtained by the minimisation of a function that considers both the bone structural stiffness and the biological cost associated with metabolic maintenance of bone tissue. The situation of multiple load conditions is considered. The remodelling law, obtained from the necessary conditions for an optimum, is derived analytically from the optimisation problem and solved numerically using a suitable finite element mesh. The formulation is applied to an implanted femur. Results of bone density and ingrowth distribution are obtained for different coating conditions. Bone ingrowth does not occur over the entire coated surfaces. Indeed, we observed regions where separation or high relative displacement occurs that preclude bone ingrowth attachment. This prediction of the model is consistent with clinical observations of bone ingrowth. Thus, this model, which detect bone ingrowth and allow modification of the interface conditions, are useful for analysis of existing stems as well as design optimisation of coating extent and location on such stems. PMID- 11784536 TI - Contribution of the nucleus to the mechanical properties of endothelial cells. AB - The cell nucleus plays a central role in the response of the endothelium to mechanical forces, possibly by deforming during cellular adaptation. The goal of this work was to precisely quantify the mechanical properties of the nucleus. Individual endothelial cells were subjected to compression between glass microplates. This technique allows measurement of the uniaxial force applied to the cell and the resulting deformation. Measurements were made on round and spread cells to rule out the influence of cell morphology on the nucleus mechanical properties. Tests were also carried out with nuclei isolated from cell cultures by a chemical treatment. The non-linear force-deformation curves indicate that round cells deform at lower forces than spread cells and nuclei. Finite-element models were also built with geometries adapted to actual morphometric measurements of round cells, spread cells and isolated nuclei. The nucleus and the cytoplasm were modeled as separate homogeneous hyperelastic materials. The models simulate the compression and yield the force-deformation curve for a given set of elastic moduli. These parameters are varied to obtain a best fit between the theoretical and experimental data. The elastic modulus of the cytoplasm is found to be on the order of 500N/m(2) for spread and round cells. The elastic modulus of the endothelial nucleus is on the order of 5000N/m(2) for nuclei in the cell and on the order of 8000N/m(2) for isolated nuclei. These results represent an unambiguous measurement of the nucleus mechanical properties and will be important in understanding how cells perceive mechanical forces and respond to them. PMID- 11784537 TI - Microstructural elasticity and regional heterogeneity in human femoral bone of various ages examined by nano-indentation. AB - The elastic modulus and hardness of secondary osteonal and interstitial bone was examined through the thickness of the cortex of human femora of various ages by nano-indentation. There was a clear difference between the stiffness and hardness of secondary osteonal and interstitial bone, the latter being stiffer (F(1,48)=56.0, P<0.001). There were some differences between the bones of different subjects; however, there were no differences that could be reliably associated with the chronological age of the subject, or with differences in location through the thickness of the cortex (F(2,48)=0.21, P=0.810). Previous studies have been equivocal in relating changes in the macroscopic 'composite' material stiffness of bone to the age of the individual. By combining the results of the nano-tests with histological measures, we were able to produce a good relationship of the microstructural properties at the matrix level with the bending modulus of whole bone (R(2)=0.88, P<0.001) and this improved further by taking into account the age of the individual (R(2)=0.94, P<0.001). Our results suggest that using differences in the volumetric proportions of secondary osteons versus interstitial bone, and the properties of these elements/structures in isolation may be a more accurate method of determining differences in elastic modulus of whole bone between individuals of various ages. PMID- 11784538 TI - Response time is more important than walking speed for the ability of older adults to avoid a fall after a trip. AB - We previously reported that the probability of an older adult recovering from a forward trip and using a "lowering" strategy increases with decreased walking velocity and faster response time. To determine the within-subject interaction of these variables we asked three questions: (1) Is the body orientation at the time that the recovery foot is lowered to the ground ("tilt angle") critical for successful recovery? (2) Can a simple inverted pendulum model, using subject specific walking velocity and response time as input variables, predict this body orientation, and thus success of recovery? (3) Is slower walking velocity or faster response time more effective in preventing a fall after a trip? Tilt angle was a perfect predictor of a successful recovery step, indicating that the recovery foot placement must occur before the tilt angle exceeds a critical value of between 23 degrees and 26 degrees from vertical. The inverted pendulum model predicted the tilt angle from walking velocity and response time with an error of 0.4+/-2.2 degrees and a correlation coefficient of 0.93. The model predicted that faster response time was more important than slower walking velocity for successful recovery. In a typical individual who is at risk for falling, we predicted that a reduction of response time to a normal value allows a 77% increase in safe walking velocity. The mathematical model produced patient specific recommendations for fall prevention, and suggested the importance of directing therapeutic interventions toward improving the response time of older adults. PMID- 11784539 TI - Streaming potentials maps are spatially resolved indicators of amplitude, frequency and ionic strength dependant responses of articular cartilage to load. AB - Streaming potential distributions were measured on the surface of articular cartilage in uniaxial unconfined compression using a linear array of microelectrodes. Potential profiles were obtained for sinusoidal and ramp/stress relaxation displacements and exhibited dependencies on radial position, sinusoidal amplitude and frequency, time during stress relaxation, and on ionic strength. The measurements agreed with trends predicted by biphasic and related models. In particular, the absolute potential amplitude was maximal at the disk center, as was the predicted fluid pressure and the potential gradient (the electric field) was seen to be maximal at the disk periphery, as was the predicted fluid velocity. We also observed a similarity between non-linear behavior of streaming potential amplitude and load amplitude with respect to sinusoidal displacement amplitude. Taken together, these results support many of the phenomena concerning relative fluid-solid movement and fluid pressurization predicted by biphasic and related models, and they indicate the general utility of spatially resolved measurements of streaming potentials for the investigation of electromechanical phenomena in tissues. For example, these streaming potential maps could be used to non-destructively diagnose cartilage extracellular matrix composition and function, as well as to quantify spatially and temporally varying physical signals in cartilage that can induce cellular and extracellular biological responses to load. PMID- 11784540 TI - Superficial aponeurosis of human gastrocnemius is elongated during contraction: implications for modeling muscle-tendon unit. AB - Two questions were addressed in this study: (1) how much strain of the superficial aponeurosis of the human medial gastrocnemius muscle (MG) was obtained during voluntary isometric contractions in vivo, (2) whether there existed inhomogeneity of the strain along the superficial aponeurosis. Seven male subjects, whose knees were extended and ankles were flexed at right angle, performed isometric plantar flexion while elongation of superficial aponeurosis of MG was determined from the movements of the intersections made by the superficial aponeurosis and fascicles using ultrasonography. The strain of the superficial aponeurosis at the maximum voluntary contraction, estimated from the elongation and length data, was 5.6+/-1.2%. There was no significant difference in strain between the proximal and distal parts of the superficial aponeurosis. Based on the present result and that of our previous study for the same subjects (J. Appl. Physiol 90 (2001) 1671), a model was formulated for a contracting uni pennate muscle-tendon unit. This model, which could be applied to isometric contractions at other angles and therefore of wide use, showed that similar strain between superficial and deep aponeuroses of MG contributed to homogeneous fascicle length change within MG during contractions. These findings would contribute to clarifying the functions of the superficial aponeurosis and the effects of the superficial aponeurosis elongation on the whole muscle behavior. PMID- 11784541 TI - Numerical study of hemodynamics and wall mechanics in distal end-to-side anastomoses of bypass grafts. AB - The development and progress of distal anastomotic intimal hyperplasia seems to be promoted by altered flow conditions and intramural stress distributions at the region of the artery-graft junction of vascular bypass configurations. From clinical observations, it is known that intimal hyperplasia preferentially occurs at outflow anastomoses of prosthetic bypass grafts. In order to gain a deeper insight into post-operative disease processes, and subsequently, to contribute to the development of improved vascular reconstructions with respect to long term patency rates, detailed studies are required. In context with in vivo experiments, this study was designed to analyze the flow dynamics and wall mechanics in anatomically correct bypass configurations related to two different surgical techniques and resulting geometries (conventional geometry and Miller cuff). The influence of geometric conditions and of different compliance of synthetic graft, the host artery and the interposed venous cuff on the hemodynamic behavior and on the wall stresses are investigated. The flow studies apply the time-dependent, three-dimensional Navier-Stokes equations describing the motion of an incompressible Newtonian fluid. The vessel walls are described by a geometrically non-linear shell structure. In an iterative coupling procedure, the two problems are solved by means of the finite element method. The numerical results demonstrate non-physiological flow patterns in the anastomotic region. Strongly skewed axial velocity profiles and high secondary velocities occur downstream the artery-graft junction. On the artery floor opposite the junction, flow separation and zones of recirculation are found. The wall mechanical studies show that increased compliance mismatch leads to increased intramural stresses, and thus, may have a proliferative influence on suture line hyperplasia, as it is observed in the in vivo study. PMID- 11784542 TI - Biomechanical effects of intraspecimen variations in tissue modulus for trabecular bone. AB - Although recent nanoindentation studies have revealed the existence of substantial variations in tissue modulus within single specimens of trabecular bone, little is known regarding the biomechanical effects of such intraspecimen variations. In this study, high-resolution finite element modeling was used to investigate these effects. With limited literature information on the spatial distribution of intraspecimen variations in tissue modulus, two plausible spatial distributions were evaluated. In addition, three specimens (human femoral neck, human vertebral body, and bovine proximal tibia) were studied to assess the role of trabecular architecture. Results indicated that for all specimen/distribution combinations, the apparent modulus of the whole specimen decreased nonlinearly with increasing coefficient of variation (COV) of tissue modulus within the specimen. Apparent modulus decreased by <4% when tissue modulus COV was increased from 0% to 20% but decreased by 7-24%, depending on the assumed spatial distribution, for an increase in tissue modulus COV from 20% to 50%. For compressive loading to the elastic limit, increasing tissue modulus COV from 20% to 50% caused up to a 28-fold increase in the amount of failed tissue, depending on assumed spatial distribution and trabecular architecture. We conclude that intraspecimen variations in tissue modulus, if large, may have appreciable effects on trabecular apparent modulus and tissue-level failure. Since the observed effects depended on the assumed spatial distribution of the tissue modulus variations, a description of such distributions, particularly as a function of age, disease, and drug treatment, may provide new insight into trabecular bone structure-function relationships. PMID- 11784543 TI - Trabecular bone adaptation with an orthotropic material model. AB - Most bone adaptation algorithms, that attempt to explain the connection between bone morphology and loads, assume that bone is effectively isotropic. An isotropic material model can explain the bone density distribution, but not the structure and pattern of trabecular bone, which clearly has a mechanical significance. In this paper, an orthotropic material model is utilized to predict the proximal femur trabecular structure. Two hypotheses are combined to determine the local orientation and material properties of each element in the model. First, it is suggested that trabecular directions, which correspond to the orthotropic material axes, are determined locally by the maximal principal stress directions due to the multiple load cases (MLC) the femur is subject to. The second hypothesis is that material properties in each material direction can be determined using directional stimuli, thus extending existing adaptation algorithms to include directionality. An algorithm is utilized, where each iteration comprises of two stages. First, material axes are rotated to the direction of the largest principal stress that occurs from a multiple load scheme applied to the proximal femur. Next, material properties are modified in each material direction, according to a directional stimulus. Results show that local material directions correspond with known trabecular patterns, reproducing all main groups of trabeculae very well. The local directional stiffnesses, degree of anisotropy and density distribution are shown to conform to real femur morphology. PMID- 11784544 TI - Discriminating the loosening behaviour of cemented hip prostheses using measurements of migration and inducible displacement. AB - In vitro pre-clinical tests of hip prostheses have not yet been developed to the extent that inferior prostheses can be 'screened-out' prior to animal or clinical trials. This paper reports the experimental part of a project to develop a pre clinical testing platform for cemented femoral hip implants. It is based on the clinical observation (Karrholm et al. JBJS, 76B (1994) 912-916) that higher subsidence (distal migration) correlates with early revision of hip prostheses. A protocol to measure the relative movement between implant and bone was designed to test whether or not such a measurement, if made in a laboratory, could discriminate between hip prostheses. The protocol was applied to the Lubinus SPII prosthesis (W. Link, Germany) and a Muller Curved Stem (JRI Ltd., UK)-these prostheses were chosen because they are known to have different loosening rates in vivo. Five prostheses of each design were tested. The migration, the rate-of migration, and the inducible displacement of each prosthesis was recorded over two million cycles of loading. For each implant, rapid initial migration was found, followed by a period of steady-state migration. In the majority of cases, the prostheses migrated medially, distally and posteriorly. On average, the Lubinus migrated less than the Muller in all directions. The average Lubinus migration was less than half that of the Muller, and this difference was significant at a level of p=0.05. Inducible displacement was greater for the Muller compared to the Lubinus. Furthermore, the inducible displacement decreased over time for the majority of Lubinus prostheses whereas it increased over time for the majority of the Muller prostheses leading to the conclusion that a rapid pre-clinical test based on measurement of inducible displacement may be possible. PMID- 11784545 TI - Simulation of a knee joint replacement during a gait cycle using explicit finite element analysis. AB - The stress distribution within the polyethylene insert of a total knee joint replacement is dependent on the kinematics, which in turn are dependent on the design of the articulating surfaces, the relative position of the components and the tension of the surrounding soft tissues. Implicit finite element analysis techniques have been used previously to examine the polyethylene stresses. However, these have essentially been static analyses and hence ignored the influence of the kinematics. The aim of this work was to use an explicit finite element approach to simulate both the kinematics and the internal stresses within a single analysis. A simulation of a total knee joint replacement subjected to a single gait cycle within a knee wear simulator was performed and the results were compared with experimental data.The predicted kinematics were in close agreement with the experimental data. Various solution-dependent parameters were found to have little influence on the predicted kinematics. The predicted stresses were found to be dependent on the mesh density. This study has shown that an explicit finite element approach is capable of predicting the kinematics and the stresses within a single analysis at relatively low computational cost. PMID- 11784546 TI - Crank inertial load affects freely chosen pedal rate during cycling. AB - Cyclists seek to maximize performance during competition, and gross efficiency is an important factor affecting performance. Gross efficiency is itself affected by pedal rate. Thus, it is important to understand factors that affect freely chosen pedal rate. Crank inertial load varies greatly during road cycling based on the selected gear ratio. Nevertheless, the possible influence of crank inertial load on freely chosen pedal rate and gross efficiency has never been investigated. This study tested the hypotheses that during cycling with sub-maximal work rates, a considerable increase in crank inertial load would cause (1) freely chosen pedal rate to increase, and as a consequence, (2) gross efficiency to decrease. Furthermore, that it would cause (3) peak crank torque to increase if a constant pedal rate was maintained. Subjects cycled on a treadmill at 150 and 250W, with low and high crank inertial load, and with preset and freely chosen pedal rate. Freely chosen pedal rate was higher at high compared with low crank inertial load. Notably, the change in crank inertial load affected the freely chosen pedal rate as much as did the 100W increase in work rate. Along with freely chosen pedal rate being higher, gross efficiency at 250W was lower during cycling with high compared with low crank inertial load. Peak crank torque was higher during cycling at 90rpm with high compared with low crank inertial load. Possibly, the subjects increased the pedal rate to compensate for the higher peak crank torque accompanying cycling with high compared with low crank inertial load. PMID- 11784547 TI - Measurement of finite-strain dependent permeability of biomembranes. AB - A complete understanding of fluid exchanges in tissues and organs requires knowledge of the permeability of their delimiting membranes as a function of the finite strain that they experience. One reason for the current dearth of data in the literature is the need for new theoretically motivated experimental approaches. In this paper, we use a general scaling to identify non-dimensional parameters that are measured easily by combining a simple pressure-driven diffusion chamber with a method to induce equibiaxial and homogeneous finite strains that can be measured via a non-contacting video system. Illustrative results on excised bovine epicardium reveal a nonlinear relationship between a non-dimensional permeability and finite strain up to stretches of 60%. PMID- 11784548 TI - Evaluation and calibration of an electromagnetic tracking device for biomechanical analysis of lifting tasks. AB - Electromagnetic motion tracking devices are increasingly used as a kinematic measuring tool. The aim of this study was to evaluate a long-range transmitter in an environment with a conventional force plate present in order to assess its suitability for further biomechanical applications. Using a calibration apparatus developed in our lab and Optotrack measurements, the performances of the Motion Star were evaluated. Positions and orientations were measured in a 140 x 80 x 120 cm(3) space centered on the force plate. Using a mathematical model developed at Queen's University, these data were calibrated. Errors on position and orientation were less than 150 mm and 10 degrees before calibration of the Motion Star, and less than 20mm and 2 degrees after calibration, with no differences between data collected with the force plate switched on/off. These errors did not depend on sensor orientation. Variability of the signal was small indicating minimal noise. Field distortion was the largest source of measurement error, which increased with the distance between the transmitter and the sensor and the proximity of the sensor to the force plate. Before its use for biomechanical analysis of lifting tasks and validation of dynamic models using force plate data, the data from electromagnetic motion tracking devices must be calibrated to decrease the errors due to electromagnetic field distortion. PMID- 11784549 TI - Dependence of release variables in the shot put. PMID- 11784550 TI - Alzheimer's disease. Unravelling the disease process. PMID- 11784551 TI - Alzheimer's disease. How can my mind go AWOL? PMID- 11784552 TI - Autism. The search for susceptibility genes. PMID- 11784553 TI - Autism. Times of hilarity and panic. PMID- 11784554 TI - BRCA1 and BRCA2 in breast cancer. PMID- 11784555 TI - My adventure with breast cancer. PMID- 11784556 TI - Cholera. A toxin with emerging therapeutic potential. PMID- 11784557 TI - Cholera. Grandmothers wheeled in barrows. PMID- 11784558 TI - Terminal deletion of 1p36. PMID- 11784559 TI - Chromosome deletions. Looking beyond disability. PMID- 11784560 TI - Chronic myeloid leukemia. Sceptical scientists. PMID- 11784561 TI - Thriving with chronic myeloid leukaemia. PMID- 11784562 TI - Coeliac disease. An inappropriate immune response. PMID- 11784563 TI - Coeliac disease. Tricky to find, hard to treat, impossible to cure. PMID- 11784564 TI - Congenital deafness. A difficult organ to work with. PMID- 11784565 TI - Congenital deafness. Not a disability. PMID- 11784566 TI - Congenital heart disease. Mending the tiniest hearts. PMID- 11784567 TI - Congenital heart disease. A misunderstood illness. PMID- 11784568 TI - Cystic fibrosis. Difficulties of gene therapy. PMID- 11784569 TI - Cystic fibrosis. Genetically programmed to self-destruct. PMID- 11784570 TI - Diabetes. Islet cell transplantation. PMID- 11784571 TI - Diabetes. Eat before drinking. PMID- 11784572 TI - Down's syndrome. A complicated genetic insult. PMID- 11784573 TI - Down's syndrome. A complete human being. PMID- 11784574 TI - Muscular dystrophy through an evolutionary lens. PMID- 11784575 TI - Duchenne muscular dystrophy. See me graduate. PMID- 11784576 TI - Dyskeratosis congenita. A disease of premature ageing. PMID- 11784577 TI - Dyskeratosis congenita. Jake's story. PMID- 11784578 TI - Gaucher's disease. Enzyme therapy is not enough. PMID- 11784579 TI - Gaucher's disease. Nose bleeds and bruising. PMID- 11784580 TI - Haemoglobin disorders. A dynamic system. PMID- 11784581 TI - Haemoglobin disorders. Shortage of blood and failure to thrive. PMID- 11784582 TI - Haemophilia. Gene mutations and pedigrees. PMID- 11784583 TI - Haemophilia. This bad blood. PMID- 11784584 TI - Hereditary ataxia. An unfolded protein. PMID- 11784585 TI - Hereditary ataxia. Finding balance. PMID- 11784586 TI - Huntington's disease. Expanding horizons for treatment. PMID- 11784587 TI - Huntington's disease. A sports star and a cook. PMID- 11784588 TI - Leprosy. Oldest and most feared disease. PMID- 11784589 TI - Leprosy. Pots and pans fell out of my hands. PMID- 11784590 TI - Malaria. A voracious creature. PMID- 11784591 TI - Malaria. It was a silly day to be sick. PMID- 11784592 TI - Meningitis. Outcome of a complex interaction. PMID- 11784593 TI - Meningitis. The worst days of my life. PMID- 11784594 TI - Osteogenesis imperfecta. A disease of the osteoblast. PMID- 11784595 TI - Osteogenesis imperfecta. A life not so fragile. PMID- 11784596 TI - Parkinson disease. Stem cell transplantation. PMID- 11784597 TI - Parkinson's disease. A disease that takes you unawares. PMID- 11784598 TI - Porphyria. Painful photosensitivity. PMID- 11784599 TI - Porphyria. Allergic to the sun. PMID- 11784600 TI - Prematurity. Timing of parturition. PMID- 11784601 TI - Prematurity. Everyday griefs and joys. PMID- 11784602 TI - Prion diseases. A rogue protein. PMID- 11784603 TI - Prion diseases. An overwhelming irrational fear. PMID- 11784604 TI - Prostate cancer. A small organ with a vital function. PMID- 11784605 TI - Prostatic cancer. Never enough information. PMID- 11784606 TI - Rh-deficiency syndrome. PMID- 11784607 TI - Red cell antigens. The fetus as a patient. PMID- 11784608 TI - Schizophrenia. Weird world inside the brain. PMID- 11784609 TI - Schizophrenia. Saved by Ezmerelda. PMID- 11784610 TI - Sepsis. A myriad of responses. PMID- 11784611 TI - Sepsis. Beauty marks. PMID- 11784612 TI - Sitosterolaemia. Dietary cholesterol absorption. PMID- 11784613 TI - Too young to be having a heart attack. PMID- 11784614 TI - Systemic lupus erythematosus. A disease with a complex pathogenesis. PMID- 11784615 TI - Systemic lupus erythematosus. Not just bendy joints. PMID- 11784616 TI - Children as a saleable commodity. PMID- 11784617 TI - Importance of asymmetrical dimethylarginine in cardiovascular risk. PMID- 11784618 TI - Untangling vascular dementia. PMID- 11784619 TI - An illuminating new step in visual-pigment regeneration. PMID- 11784620 TI - SAD-help arrives with the dawn? PMID- 11784621 TI - Molecular basis of the sweet tooth? PMID- 11784622 TI - Effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey: a cross-sectional study. AB - BACKGROUND: Passive smoking is widespread, and environmental tobacco smoke contains many potent respiratory irritants. This analysis aimed to estimate the effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey. METHODS: This analysis included data from 7882 adults (age 20-48 years) who had never smoked, from 36 centres in 16 countries. Information on passive smoking, respiratory symptoms, asthma, and allergic rhinitis was gathered through a structured interview. Spirometry and methacholine challenge were carried out, and total and specific IgE were measured. The effect of passive smoking was estimated by means of logistic and multiple linear regression for each country and combined across countries by random-effects meta-analysis. FINDINGS: In 12 of the 36 centres, more than half the participants were regularly involuntarily exposed to tobacco smoke. The prevalence of passive smoking in the workplace varied from 2.5% in Uppsala, Sweden, to 53.8% in Galdakao, Spain. Passive smoking was significantly associated with nocturnal chest tightness (odds ratio 1.28 [95% CI 1.02 to 1.60]), nocturnal breathlessness (1.30 [1.01 to 1.67]), breathlessness after activity (1.25 [1.07 to 1.47]), and increased bronchial responsiveness (effect -0.18 [-0.30 to -.05]). Passive smoking in the workplace was significantly associated with all types of respiratory symptoms and current asthma (odds ratio 1.90 [95% CI 0.90 to 2.88]). No significant association was found between passive smoking and total serum IgE. INTERPRETATION: Passive smoking is common but the prevalence varies widely between different countries. Passive smoking increased the likelihood of experiencing respiratory symptoms and was associated with increased bronchial responsiveness. Decreasing involuntary exposure to tobacco smoke in the community, especially in workplaces, is likely to improve respiratory health. PMID- 11784623 TI - Uses of error: examination. PMID- 11784624 TI - Death by homicide, suicide, and other unnatural causes in people with mental illness: a population-based study. AB - BACKGROUND: People with mental illness are at great risk of suicide, but little is known about their risk of death from other unnatural causes. No study has commented on their risk of being victims of homicide; public concern is pre occupied with their role as perpetrators. We aimed to calculate standardised mortality ratios (SMRs) and directly standardised rate ratios for death by homicide, suicide, and accident in people admitted to hospital because of mental illness. METHOD: We did a population-based study in which we linked the data for 72208 individuals listed in the Danish Psychiatric Case Register between 1973 and 1993, and who died before Dec 31, 1993, with data in the Danish National Register of Causes of Death. FINDINGS: 17892 (25%) patients died from unnatural causes. Our results show raised SMRs for homicide, suicide, and accident for most psychiatric diagnoses irrespective of sex. The all-diagnosis SMRs for women and men, respectively, were: 632 (95% CI 517-773) and 609 (493-753) for homicide, 1356 (1322-1391) and 1212 (1184-1241) for suicide, and 318 (305-332) and 466 (448 484) for accident. We recorded an increased risk of dying by homicide in men with schizophrenia and in individuals with affective psychosis. The highest risks of death by homicide and accident were in alcoholism and drug use, whereas the highest risks of suicide were in drug use. INTERPRETATION: People with mental disorders, including severe mental illness, are at increased risk of death by homicide. Strategies to reduce mortality in the mentally ill are correct to emphasise the high risk of suicide, but they should also focus on other unnatural causes of death. PMID- 11784625 TI - Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. AB - BACKGROUND: The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric-oxide synthase, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. We investigated the relation between cardiovascular risk factors and plasma ADMA concentration in a cohort of haemodialysis patients (n=225), and tested the predictive power of ADMA for mortality and cardiovascular outcomes. METHODS: Patients had standard dialysis three times a week. We accurately recorded cardiovascular events over a mean follow-up of 33.4 months (SD 14.6); these events were reviewed by a panel of physicians. We identified correlates of plasma ADMA by univariate and multivariate analyses. FINDINGS: On univariate analysis, ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration, and was inversely related to serum albumin concentration. On multivariate analysis, only plasma fibrinogen (p=0.0001) and serum albumin (p=0.04) concentrations were independently related to plasma ADMA concentration (multiple r=0.44, p=0.0001). 83 patients died, 53 (64%) by cardiovascular causes. In a Cox's proportional hazards model, plasma ADMA ranked as the second factor predicting overall mortality (hazard ratio 1.26, 95% Cl 1.11-1.41, p=0.0001) and cardiovascular events (1.17, 1.04-1.33, p=0.008). INTERPRETATION: In haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure. PMID- 11784626 TI - Sensitivity of a clinical examination to predict need for radiography in children with ankle injuries: a prospective study. AB - BACKGROUND: Radiographs are ordered routinely for children with ankle trauma. We assessed the predictive value of a clinical examination to identify a predefined group of low-risk injuries, management of which would not be affected by absence of a radiograph. We aimed to show that no more than 1% of children with low-risk examinations (signs restricted to the distal fibula) would have high-risk fractures (all fractures except avulsion, buckle, and non-displaced Salter-Harris I and II fractures of the distal fibula), and to compare the potential reduction in radiography in children with low-risk examinations with that obtained by application of the Ottawa ankle rules (OAR). METHODS: Standard clinical examinations and subsequent radiographs were prospectively and independently evaluated in two tertiary-care paediatric emergency departments in North America. Eligible participants were healthy children aged 3-16 years with acute ankle injuries. Sample size, negative and positive predictive values, sensitivity, and specificity were calculated. McNemar's test was used to compare differences in the potential reduction in radiographs between the low-risk examination and the OAR. FINDINGS: 607 children were enrolled; 581 (95.7%) received follow-up. None of the 381 children with low-risk examinations had a high-risk fracture (negative predictive value 100% [95% CI 99.2-100]; sensitivity 100% [93.3-100]). Radiographs could be omitted in 62.8% of children with low-risk examinations, compared with only 12.0% reduction obtained by application of the OAR (p<0.0001). INTERPRETATION: A low-risk clinical examination in children with ankle injuries identifies 100% of high-risk diagnoses and may result in greater reduction of radiographic referrals than the OAR. PMID- 11784627 TI - Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. AB - BACKGROUND: Diagnosis and management of idiopathic thrombocytopenic purpura (ITP) have been based primarily on expert opinion and practice guidelines rather than on evidence. We have used a registry to prospectively survey the presenting features and the diagnostic evaluation and management practices used for children with ITP worldwide. METHODS: We used the Intercontinental Childhood ITP Registry which had been widely advertised. 209 physicians from 136 institutions in 38 countries participated by submitting data for each of their newly diagnosed patients. Data from 2031 children with ITP was registered between June, 1997, and May, 2000, and we analysed 6-month follow-up data from 1496 children. FINDINGS: There was a peak in occurrence of childhood ITP during spring and a nadir in the autumn. Mean initial platelet count was 15.4x10(9)/L (SD 19.7). 1447 (73%) of 1976 children were admitted to hospital. Initial management consisted of no drug treatment in 612 (31%), intravenous immunoglobulin in 576 (29%), corticosteroids in 651 (33%), or both in 137 (7%) patients. Intracranial haemorrhage was reported in two patients. INTERPRETATION: The variable approaches to management of childhood ITP demonstrate the need for prospective clinical trials, which should be feasible within such a study group. PMID- 11784628 TI - A juicy problem. PMID- 11784629 TI - Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. AB - Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease. We investigated the association of ADMA concentration in serum with risk of acute coronary events. We did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (>0.62 micromol/L) had a 3.9-fold (95% CI 1.25-12.3, p=0.02) increase in risk of acute coronary events compared with the other quartiles. Our findings suggest that ADMA is a predictor of acute coronary events. PMID- 11784630 TI - Shortage of vaccines during a yellow fever outbreak in Guinea. AB - A yellow fever epidemic erupted in Guinea in September, 2000. From Sept 4, 2000, to Jan 7, 2001, 688 instances of the disease and 225 deaths were reported. The diagnosis was laboratory confirmed by IgM detection in more than 40 patients. A mass vaccination campaign was limited by insufficient international stocks. After the epidemic in Guinea, the International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control decided that 2 million doses of 17D yellow fever vaccine, being stored as part of a UNICEF stockpile, should be used only in response to outbreaks. PMID- 11784631 TI - Blood-pressure reduction and cardiovascular risk in HOPE study. AB - In the Heart Outcomes Prevention Evaluation (HOPE) study, use of the angiotensin converting-enzyme inhibitor ramipril was associated with a 22% relative risk reduction in cardiovascular death, myocardial infarction, or stroke, despite only a modest reduction in blood pressure (23.3 mm Hg systolic). To test the hypothesis that the benefits seen were not due to reduced blood pressure alone, we calculated blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. We found that the benefits seen in HOPE were around three times greater than predicted from these calculations. In this well treated and largely normotensive population with coronary disease, but good left-ventricular function, the benefits from ramipril were additive to other proven therapies in normotensive patients and in those with higher baseline blood pressure. PMID- 11784632 TI - Immunisation status of children adopted from China. AB - Many children adopted from China have antibody titres that do not correlate with those expected from their medical records. We have compared the concentrations of antibodies to poliomyelitis, diphtheria, and tetanus in children adopted from China, those adopted from other countries, and those vaccinated in the Netherlands and the UK. About 30% of children adopted from China did not have adequate protection from tetanus, diphtheria, or poliomyelitis, despite having complete vaccination recorded in their vaccination documents. These children, unlike those adopted from other countries who have documented evidence of adequate vaccination status, should be tested for antibody concentrations or reimmunised. PMID- 11784633 TI - WHO commission announces bold plan for world's poor. PMID- 11784636 TI - Red or white wine with your turkey, sir? PMID- 11784638 TI - Have you heard the one about the prefrontal cortex? PMID- 11784640 TI - European Parliament considers case for European public-health agency. PMID- 11784639 TI - War, bioterrorism, and the political landscape. PMID- 11784641 TI - Australian Aboriginal leaders tackle welfare of indigenous population. PMID- 11784642 TI - Government advisory body rules out CJD link to polio vaccine. PMID- 11784644 TI - Goodbye Franc, Mark, Guilder, Escudoellipsis. PMID- 11784643 TI - S Africa must treat HIV-infected pregnant women, says high court judge. PMID- 11784645 TI - Ghana: defining the African challenge. AB - In 1957, Ghana became the first African nation to achieve independence from its colonial ruler. But since then Ghana has suffered mixed political and economic fortunes. The health of Ghana's people and the country's progress in modernising its health-care system have fluctuated according to peaks and troughs in West African history. Some critics see Ghana's course since independence as a promise unfulfilled. Others view Ghana as a model for North-South cooperation, which could be rolled out across the whole of Africa. In November, 2001, I visited hospitals and health centres in both rural and urban settings to investigate the present state of Ghanaian medicine. The picture I saw was one of a country clear about what it wants to do but divided about how it should achieve its goals. If Ghana is to be a model for Africa, it is more a model of problems to be faced than solutions discovered. PMID- 11784646 TI - Coroner Wakley: two remarkable eyewitness accounts. PMID- 11784647 TI - How the heart was held in medieval art. PMID- 11784648 TI - Clinical picture: A haemophiliac patient with synovial osteochondromatosis of the ankle. PMID- 11784649 TI - Charles Dickens: a neglected diagnosis. PMID- 11784650 TI - Flora's legacy. PMID- 11784651 TI - Screening for breast cancer with mammography. PMID- 11784652 TI - Screening for breast cancer with mammography. PMID- 11784653 TI - Screening for breast cancer with mammography. PMID- 11784654 TI - Screening for breast cancer with mammography. PMID- 11784655 TI - Screening for breast cancer with mammography. PMID- 11784656 TI - Screening for breast cancer with mammography. PMID- 11784657 TI - Screening for breast cancer with mammography. PMID- 11784658 TI - Screening for breast cancer with mammography. PMID- 11784660 TI - Human parvovirus B19 and meningoencephalitis. PMID- 11784661 TI - Macrolide treatment after coronary stent placement. PMID- 11784663 TI - Turner's syndrome. PMID- 11784664 TI - Polychemotherapy for early breast cancer. PMID- 11784666 TI - Is it really food poisoning? PMID- 11784667 TI - Follow-up of type III hyperlipoproteinaemia in a child. PMID- 11784669 TI - Prothrombin time to assess fulminant hepatic failure. PMID- 11784670 TI - The teaching of appropriate use of antimicrobials. PMID- 11784671 TI - Decision analysis in patients' care. PMID- 11784672 TI - Decision analysis in patients' care. PMID- 11784673 TI - Usefulness of foreign aid for health care in less-developed countries. PMID- 11784695 TI - Naturally occurring free D-aspartate is a nuclear component of cells in the mammalian hypothalamo-neurohypophyseal system. AB - It is generally believed that only L-amino acids have a physiological role in species other than bacteria. Recently, the existence of some D-amino acids, particularly D-aspartate, in various organs of several higher animals has been reported. Here we demonstrate that naturally occurring free D-aspartate is localized subcellularly to the heterochromatin in the nucleoli (but not in either the dendrites or axonal terminals) of magnocellular neurosecretory neurons in the rat hypothalamus, and also of microglia and pericytes in the posterior pituitary. Our results imply that naturally occurring free D-aspartate might have a physiological role in nuclear function in mammals. The findings provide new insight for the biological function of D-stereoisomers of amino acids as well as the organization of the nucleus of at least some eukaryotic cells. PMID- 11784696 TI - Immunolocalisation of 14-3-3 isoforms in normal and scrapie-infected murine brain. AB - The appearance of 14-3-3 proteins in the cerebrospinal fluid is characteristic of some neurodegenerative conditions which include sporadic Creutzfeldt-Jakob disease. Although 14-3-3 proteins are physiochemically well characterised and are known to be present in neuronal cells little is known of the neuroanatomical localisation of the individual isoforms. Using 14-3-3 isoform specific antibodies we have examined the distribution of the isoforms in normal murine brain and the changes observed during neurodegeneration as a result of ME7 scrapie infection. In normal brain there are two major patterns of immunolabelling. The beta, gamma, eta and zeta isoforms which exhibit a similar distribution pattern showing labelling of neuronal cell bodies often in particular anatomical nuclei. However the individual isoforms exhibit variation revealing subtle differences in location. The tau isoform was found only in the hippocampus and medulla, and the epsilon isoform was found throughout grey matter of the CNS. In the scrapie infected murine brain, where severe pathological changes occur during the course of the disease, significant differences in the 14-3-3 isoform distribution were observed in the hippocampus and in the thalamus. Importantly, both the 14-3-3 eta isoform and prion protein were seen in the same neurones in both the cerebellar roof nuclei and in the lateral hypothalamic nuclei. Our study of 14-3-3 isoform distribution in adult murine brain clearly demonstrates a heterogeneous pattern of neurolocation for specific 14-3-3 isoforms. The fact that isoform labelling in terminal scrapie CNS is lost in some brain areas, but increases in others, suggests that the processing of these proteins during neurodegeneration may be much more complex than previously recognised. PMID- 11784697 TI - Cloning and characterization of guanine deaminase from mouse and rat brain. AB - A search for genes differentially expressed in the rat striatum revealed a gene fragment with a ventral to dorsal striatal expression pattern. The sequence of the fragment was used to isolate mouse and rat clones that upon sequencing were identified as homologous to human guanine deaminase. Here we report the distribution of guanine deaminase in the rodent brain. In situ hybridization localization of the encoding mRNA showed a distribution primarily in forebrain areas including cortical pyramidal neurons, ventral striatal medium spiny neurons, hippocampal pyramidal neurons in CA3-CA1 and granule cells in the dentate gyrus, and neurons of the amygdala. Immunohistochemistry using antibodies raised against peptide fragments derived from the guanine deaminase protein sequence showed localization of guanine deaminase in areas predicted by the mRNA distribution. In addition to immunolabeling of neurons in the cerebral cortex, hippocampus, striatum and amygdala there was also labeling in the terminal fields of these neurons including the thalamus, globus pallidum and substantia nigra. A functional histochemical assay that demonstrates the site of guanine deamination shows guanine deaminase activity in a pattern that matched the immunohistochemical localization. The cellular distribution of guanine deaminase to distal areas of the cell including terminals and dendrites was additionally demonstrated by the expression of recombinant guanine deaminase in transformed cortical neurons in culture. In summary we have described the isolation and characterization of mouse and rat guanine deaminase. The expression of guanine deaminase is primarily restricted to forebrain neurons. A histochemical assay was used to localize guanine deaminase activity to the dendrites and axons of neurons expressing guanine deaminase. PMID- 11784698 TI - The expression of the glutamate re-uptake transporter excitatory amino acid transporter 1 (EAAT1) in the normal human CNS and in motor neurone disease: an immunohistochemical study. AB - A monoclonal antibody to excitatory amino acid transporter 1 (EAAT1) has been generated which robustly stains paraffin-embedded, formaldehyde-fixed as well as snap-frozen human post-mortem brain tissue. We have used this antibody to map the distribution of EAAT1 throughout normal human CNS tissue. In addition this antibody has been used to perform a semi-quantitative immunohistochemical analysis of the expression of EAAT1 in motor cortex and cervical cord tissue taken from motor neurone disease cases (n=17) and neurologically normal controls (n=12). By comparing the relative optical density measurements of identical regions of motor cortex and cervical spinal cord an increase in the expression levels of EAAT1 was observed in motor neurone disease tissue compared to the control tissue and in both motor cortex and cervical spinal cord (9-17% and 13 33% increases respectively). EAAT1 was observed to be the most abundant transporter in more "caudal" brain regions such as the diencephalon and brainstem and its expression in other regions was frequently more uniform than that of EAAT2. In the motor cortex, EAAT1 immunoreactivity was present in all grey matter laminae, with some staining of individual astrocytes in the white matter. In spinal cord, EAAT1 immunoreactivity was strongest in the substantia gelatinosa. In the ventral horn, motor neurones were surrounded with a dense rim of perisomatic EAAT1 immunoreactivity, and the neuropil showed diffuse staining. Additional studies using double-labelling immunocytochemistry demonstrated that astrocytic co-localisation of EAAT1 and EAAT2 may occasionally be seen, but was not widespread in the human CNS and that in general astrocytes were positive for either EAAT1 or EAAT2. These results demonstrate that the EAAT1 has a widespread abundance throughout all regions of the human CNS examined and that there exist discrete populations of astrocytes that are positive solely for either EAAT1 or EAAT2. Furthermore, there is evidence to suggest that altered EAAT1 expression in motor neurone disease follows a different pattern to the reported changes of EAAT2 expression in this condition, indicating that the role of glutamate transporters in the pathogenesis of motor neurone disease appears more complex than previously appreciated. PMID- 11784699 TI - A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system. AB - Rapid uptake of synaptically released glutamate via the high affinity glutamate transporter 1 (GLT1; EAAT2) is important for limiting transmitter signalling and prevents a harmful receptor overstimulation. So far, in the adult brain GLT1 protein has only been detected in astrocytes. Here, we describe the cDNA cloning of a variant of GLT1 from rat brain which is generated by alternative splicing at the 3'-end of the GLT1 cDNA. Reverse transcription-polymerase chain reaction revealed that the GLT1 variant message was present not only in brain, but also in peripheral organs. Northern blot analysis showed that in brain the mRNA of GLT1 (approximately 11 kb) is predominant while in the retina the mRNA of GLT1 variant (approximately 12.5 kb) prevails. In situ hybridization using cRNA and oligonucleotide probes, and immunocytochemistry using an antibody against a synthetic GLT1v peptide were applied in order to identify the cell types expressing GLT1 variant in the adult rat nervous system. GLT1 variant is preferentially expressed in neurons of the CNS and PNS, but is also detected in glial cells (oligodendrocytes, ependymal cells, epithelial cells of the plexus choroideus, satellite cells, and Schwann cells). In contrast to GLT1, GLT1 variant was only occasionally detected in astrocytes. Immunolabelling revealed a preferentially cytoplasmic (frequently granular) staining of neurons and glial cells, suggesting a localization of GLT1 variant protein in vesicle membranes. The studies provide evidence that the cellular expression of the GLT1 variant in the CNS is almost complementary to that of GLT1 and that the GLT1 variant does not seem to be restricted to the CNS. PMID- 11784700 TI - Cholecystokinin-immunopositive basket and Schaffer collateral-associated interneurones target different domains of pyramidal cells in the CA1 area of the rat hippocampus. AB - Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. In order to establish whether more than one population of cholecystokinin-expressing interneurone exist in the hippocampus, we have performed whole-cell current clamp recordings from interneurones located in the stratum radiatum of the hippocampal CA1 region of developing rats. Recorded neurones were filled with biocytin to reveal their axonal targets, and were tested for the presence of pro-cholecystokinin immunoreactivity. The results show that two populations of cholecystokinin-immunoreactive interneurones exist in the CA1 area (n=15 positive cells). Cholecystokinin-positive basket cells (53%) preferentially innervate stratum pyramidale and adjacent strata oriens and radiatum. A second population of cholecystokinin-positive cells, previously described as Schaffer collateral-associated interneurones [Vida et al. (1998) J. Physiol. 506, 755-773], have axons that ramify almost exclusively in strata radiatum and oriens, overlapping with the Schaffer collateral/commissural pathway originating from CA3 pyramidal cells. Two of seven of the Schaffer collateral associated cells were also immunopositive for calbindin. Soma position and orientation in stratum radiatum, the number and orientation of dendrites, and the passive and active membrane properties of the two cell populations are only slightly different. In addition, in stratum radiatum and its border with lacunosum of perfusion-fixed hippocampi, 31.6+/-3.8% (adult) or 26.8+/-2.9% (postnatal day 17-20) of cholecystokinin-positive cells were also immunoreactive for calbindin. Therefore, at least two populations of pro-cholecystokinin immunopositive interneurones, basket and Schaffer collateral-associated cells, exist in the CA1 area of the hippocampus, and are probably homologous to cholecystokinin-immunopositive basket and double bouquet cells in the isocortex. It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex. PMID- 11784701 TI - Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease. AB - Transgenic R6/1 mice incorporate a human genomic fragment containing promoter elements exon 1 and a portion of intron 2 of the Huntingtin gene responsible for Huntington's disease. They develop late-onset neurological deficits in a manner similar to the motor abnormalities of the disorder. As essential fatty acids are phospholipid components of cell membranes which may influence cell death and movement disorder phenotype, R6/1 and normal mice were randomised to receive a mixture of essential fatty acids or placebo on alternate days throughout life. Over mid-adulthood, topographical assessment of behaviour revealed R6/1 transgenics to evidence progressive shortening of stride length, with progressive reductions in locomotion, elements of rearing, sniffing, sifting and chewing, and an increase in grooming. These deficits were either not evident or materially diminished in R6/1 transgenics receiving essential fatty acids. R6/1 transgenics also showed reductions in body weight and in brain dopamine D(1)-like and D(2) like quantitative receptor autoradiography which were unaltered by essential fatty acids.These findings indicate that early and sustained treatment with essential fatty acids are able to protect against motor deficits in R6/1 transgenic mice expressing exon 1 and a portion of intron 2 of the Huntingtin gene, and suggest that essential fatty acids may have therapeutic potential in Huntington's disease. PMID- 11784702 TI - Acute administration of haloperidol induces apoptosis of neurones in the striatum and substantia nigra in the rat. AB - Chronic administration of typical neuroleptics is associated with tardive dyskinesia in some patients. This dyskinetic syndrome has been associated with loss of GABAergic markers in the basal ganglia but the cause of these GABAergic depletions remains uncertain. Haloperidol, a commonly prescribed typical neuroleptic, is known to be toxic in vitro, possibly as a consequence of its conversion to pyridinium-based metabolites and potentially by raising glutamate mediated transmission. We report here that the in vivo, acute administration of a large dose of haloperidol resulted in a microglial response indicative of neuronal damage. This was accompanied by an increase in the number of apoptotic cells in the striatum (especially in the dorsomedial caudate putamen) and in the substantia nigra pars reticulata. These apoptotic cells were characterised by the stereotaxic injection of a retrograde neuroanatomical tracer into the projection targets of the striatum and substantia nigra pars reticulata prior to the systemic injection of haloperidol. This procedure confirmed that the dying cells were neurones and demonstrated that within the striatum the majority were striatopallidal neurones though relatively high levels of apoptotic striatoentopeduncular neurones were also seen.The possibility that chronic administration of haloperidol could induce cumulative neuronal loss in the substantia nigra pars reticulata and thereby induce the pathological changes which lead to tardive dyskinesia is discussed. PMID- 11784703 TI - Relationship between sprouting axons, proteoglycans and glial cells following unilateral nigrostriatal axotomy in the adult rat. AB - Proteoglycans may modulate axon growth in the intact and injured adult mammalian CNS. Here we investigate the distribution and time course of deposition of a range of proteoglycans between 4 and 14 days following unilateral axotomy of the nigrostriatal tract in anaesthetised adult rats. Immunolabelling using a variety of antibodies was used to examine the response of heparan sulphate proteoglycans, chondroitin sulphate proteoglycans and keratan sulphate proteoglycans. We observed that many proteoglycans became abundant between 1 and 2 weeks post axotomy. Heparan sulphate proteoglycans were predominantly found within the lesion core (populated by blood vessels, amoeboid macrophages and meningeal fibroblasts) whereas chondroitin sulphate proteoglycans and keratan sulphate proteoglycans were predominantly found in the lesion surround (populated by reactive astrocytes, activated microglia and adult precursor cells). Immunolabelling indicated that cut dopaminergic nigral axons sprouted prolifically within the lesion core but rarely grew into the lesion surround. We conclude that sprouting of cut dopaminergic nigral axons may be supported by heparan sulphate proteoglycans but restricted by chondroitin sulphate proteoglycans and keratan sulphate proteoglycans. PMID- 11784704 TI - GABA(B) receptors in the median raphe nucleus: distribution and role in the serotonergic control of hippocampal activity. AB - Previous studies have shown that serotonergic neurons of the median raphe nucleus have a suppressive effect on theta synchronization in the hippocampus. Median raphe lesion, suppression of 5-HT neuronal activity by administration of GABA(A) receptor antagonist or by glutamate blockade or depletion produced long-lasting non-interrupted hippocampal theta in freely behaving rats independent of behavior and in rats anesthetized with urethane. Serotonergic neurons show a characteristic sleep-wake pattern of activity and there is evidence that GABAergic mechanisms play an important role in their regulation. In this study we analyzed the distribution and subcellular localization of GABA(B) receptors in the midbrain raphe complex using combined 5-HT/GABA(B) receptor immunohistochemistry at the light and electron microscopic levels and studied the effects of their pharmacological manipulation on hippocampal electroencephalographic activity in urethane-anesthetized rats. We found that sustained infusion of the GABA(B) receptor agonist baclofen into the median raphe nucleus, using the microdialysis technique, elicited lasting theta activity in the hippocampus. The effect was antagonized by selective GABA(B) receptor antagonists. The predominant localization of GABA(B) receptors in the median, as well as in dorsal raphe was found on serotonergic neurons which strongly indicates that the increase in theta occurrence after baclofen injection resulted from suppression of the serotonergic output originating from the median raphe. On the electron microscopic level, we found GABA(B) receptors located extrasynaptically indicating that these receptors are preferentially activated by strong inputs, i.e. when GABA released from the synaptic terminals is sufficient to spill over from the synaptic cleft. Such conditions might be satisfied during rapid eye movement sleep when GABAergic neurons in the raphe are firing at their highest rate and in rhythmic synchronized bursts. Our data indicate that midbrain raphe GABA(B) mechanisms play an important role in behavioral state control and in hippocampal activity, in particular. PMID- 11784705 TI - Activation of mu-opioid receptors in rat ventrolateral medulla selectively blocks baroreceptor reflexes while activation of delta opioid receptors blocks somato sympathetic reflexes. AB - The effects of activation of mu and delta-opioid receptors in the rostral ventrolateral medulla (RVLM) on somato-sympathetic, baroreceptor and chemoreceptor reflexes, as well as respiratory rhythmicity in sympathetic nerves, were examined in urethane anaesthetized (1.1-1.2 g/kg) and artificially ventilated Sprague-Dawley rats. Microinjection of the delta-opioid receptor agonist [D-Pen(2,5)]-enkephalin (DPDPE; 8 mM, 50 nl) bilaterally into the RVLM potently inhibited the post-inspiratory-related burst discharges of lumbar sympathetic nerve activity (LSNA) but had only limited effects on splanchnic sympathetic nerve activity (SSNA) and phrenic nerve discharge. Injection of DPDPE into the RVLM strongly attenuated the somato-sympathetic reflex (approximately 50 80%) evoked in the lumbar sympathetic nerve and splanchnic sympathetic nerve by tibial nerve stimulation but had no effect on baroreceptor reflexes and chemoreceptor reflexes evoked by aortic nerve stimulation and brief hypoxia, respectively. Injection of the mu-opioid receptor agonist, [D-Ala(2),N-Me Phe(4),Gly-ol(5)]-enkephalin (DAMGO; 4 mM, 50 nl), also elicited a greater inhibition of LSNA than SSNA accompanied by an abolition of phrenic nerve discharge. Injection of DAMGO inhibited the baroreceptor reflex without significant effect on either the somato-sympathetic or the chemoreceptor reflexes. We propose that opioid peptides diminish specific excitatory and inhibitory inputs to the presympathetic neurons in RVLM via distinct presynaptic receptor subclasses. PMID- 11784706 TI - Nitric oxide toxicity in CNS white matter: an in vitro study using rat optic nerve. AB - Excessive nitric oxide formation may contribute to the pathology occurring in diseases affecting central white matter, such as multiple sclerosis. The rat isolated optic nerve preparation was used to investigate the potential toxicity of the molecule towards such tissue. The nerves were exposed to a range of concentrations of different classes of nitric oxide donor for up to 23 h, with or without a subsequent period of recovery, and the damage assessed by quantitative histological methods. Degeneration of axons and macroglia occurred in a time- and concentration-dependent manner, the order of susceptibility being: axons>oligodendrocytes>astrocytes. Use of NONOate donors differing in half-life indicated that nitric oxide delivered in an enduring manner at relatively low concentration was more toxic than the same amount supplied rapidly at high concentration. The mechanism by which nitric oxide affects axons was studied using a donor [3-(n-propylamino)propylamine/NO adduct, PAPA/NO] with an intermediate half-life that produced selective axonopathy after a 2-h exposure (plus 2 h recovery). Axon damage was abolished if, during the exposure, Na(+) or Ca(2+) was removed from the bathing medium or the sodium channel inhibitors tetrodotoxin or BW619C89 (sipatrigine) were added. In electrophysiological experiments, the donor elicited a biphasic depolarisation. The second, larger component (occurring after 7-10 min) was associated with a block of nerve conduction and could be inhibited by tetrodotoxin. Coincident with the secondary depolarisation was a reduction in ATP levels by about 50%, an effect that was also inhibited by tetrodotoxin. It is concluded that nitric oxide, in submicromolar concentrations, can kill axons and macroglia in white matter. The findings lend support to the hypothesis that nitric oxide may be of importance to white matter pathologies, particularly those in which inducible nitric oxide synthase is expressed. The axonopathy, at least when elicited over relatively short time intervals, is likely to be caused by metabolic inhibition. As in anoxia and anoxia/aglycaemia, nitric oxide-induced destruction of axons is likely to be caused by the Ca(2+) overload that follows a reduction in ATP levels in the face of continued influx of Na(+) through voltage-dependent channels. PMID- 11784707 TI - Retinal ganglion cell death after acute retinal ischemia is an ongoing process whose severity and duration depends on the duration of the insult. AB - In adult Sprague-Dawley rats we have investigated retinal ganglion cell survival after transient intervals of retinal ischemia of 30, 45, 60, 90 or 120 min duration, induced by ligature of the ophthalmic vessels. Animals were killed 5, 7, 14, 21, 30, 60, 90 or 180 days later and densities of surviving retinal ganglion cells were estimated in retinal whole mounts by counting cells labelled with diAsp. This dye was applied, 3 days prior to death, to the ocular stump of the intraorbitally transected optic nerve. We found that retinal ganglion cell loss after retinal ischemia proceeds for different lengths of time. All the ischemic intervals induced loss of retinal ganglion cells whose severity and duration was related to the length of the ischemic interval. Following 30 or 45 min of ischemia, cell loss lasted 14 days and caused the death of 46 or 50%, respectively, of the population of retinal ganglion cells. Sixty, 90 or 120 min of retinal ischemia were followed by a period of cell loss that lasted up to 90 days and caused the death of 75%, 87% or 99%, respectively, of the population of retinal ganglion cells. We conclude that retinal ganglion cell loss after retinal ischemia is an ongoing process that may last up to 3 months after the injury and that its severity and duration are determined by the ischemic interval. PMID- 11784708 TI - A-type potassium currents dominate repolarisation of neonatal rat primary auditory neurones in situ. AB - Spiral ganglion neurones provide the afferent innervation to cochlear hair cells. Little is known of the molecular physiological processes associated with the differentiation of these neurones, which occurs up to and beyond hearing onset. We have identified novel A-type (inactivating) potassium currents in neonatal rat spiral ganglion neurones in situ, which have not previously been reported from the mammalian cochlea, presumably as a consequence of altered protein expression associated with other preparations. Under whole-cell voltage clamp, voltage steps activated both A-type and non-inactivating outward currents from around -55 mV. The amplitude of the A-type currents was dependent on the holding potential, with steady-state inactivation relieved at hyperpolarised potentials. At -60 mV (close to the resting potential in situ) the currents were approximately 30% enabled. The inactivation kinetics and the degree of inactivation varied between cells, suggesting heterogeneous expression of multiple inactivating currents. A-type currents provided around 60% of total conductance activated by depolarising voltage steps from the resting potential, and were very sensitive to bath-applied 4-aminopyridine (0.01-1 mM). Tetraethylammonium (0.1-30 mM) also blocked the majority of the A-type currents, and the non-inactivating outward current, but left residual fast inactivating A-type current. Under current clamp, neurones fired single tetrodotoxin-sensitive action potentials. 4-Aminopyridine relieved the A-type current mediated stabilisation of membrane potential, resulting in periodic small amplitude action potentials. This study provides the first electrophysiological evidence for A-type potassium currents in neonatal spiral ganglion neurones and shows that these currents play an integral role in primary auditory neurone firing. PMID- 11784709 TI - Ascending connections from the caudal part to the oral part of the spinal trigeminal nucleus in the rat. AB - The brainstem trigeminal somatosensory complex, while sharing many common aspects with the spinal somatosensory system, displays features specific to orofacial information processing. One of those is the redundant representation of peripheral structures within the various subnuclei of the complex. A functional redundancy also exists since a single sensory modality, e.g. nociception, may be processed within different subnuclei. In the present study, we addressed the question whether anatomical connections from the caudal part to the oral part of the spinal trigeminal nucleus may support topographical and functional redundancy within the rat trigeminal somatosensory complex. The retrograde tracer tetramethylrhodamine-dextran was injected iontophoretically into the oral subnucleus of anaesthetised rats. Cell bodies labelled retrogradely from the oral subnucleus were observed in laminae III-IV and V of the ipsilateral caudal subnucleus consistently, and to a lesser degree in lamina I. Such a distribution of retrogradely labelled cells suggested that specific subsets of neurones may relay nociceptive information, and others non-nociceptive information. Furthermore, intratrigeminal connections conserved the somatotopic distribution of primary afferents in the two subnuclei. First, injections of tracer in the dorsomedial and ventrolateral parts of the oral subnucleus resulted in retrograde labelling of the dorsal and ventral parts of the caudal subnucleus respectively. Second, animals that received tracer into the ventrolateral oral subnucleus displayed more caudal labelling than animals that were injected into the dorsomedial oral subnucleus. These findings show the existence of anatomical connections from the caudal part to the oral part of the spinal trigeminal nucleus in the rat. The connections conserve the somatotopic distribution of primary afferents in the two subnuclei. They provide an anatomical substrate for the indirect activation of trigeminal oral subnucleus neurones by somatosensory stimuli through the caudal subnucleus. PMID- 11784710 TI - Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals. AB - During periods of high-frequency stimulation the maintenance of synaptic transmission depends on a continued supply of synaptic vesicles. Local recycling in the terminals ensures synaptic vesicle replenishment, but the intermediate steps are still a matter of debate. We analyzed changes in synaptic vesicle pools and endosome-like organelles near the active zone in central nerve terminals during depolarization at the ultrastructural level by electron microscopy. A short, 100 ms, depolarization-induced recruitment of synaptic vesicles was observed from a reserve pool to a recruited pool, within 150 nm of the active zone, and the docked pool at the active zone was increased as well. Prolonged, 15 s or 3 min, depolarization decreased the total amount of synaptic vesicles, which was accompanied by a parallel increase in size and amount of endosome-like organelles. After a period of rest, the number of endosome-like organelles decreased and the amount of synaptic vesicles was restored to control level. The endocytotic nature of part of the endosome-like organelles after 15 s and 3 min depolarization was indicated by their labeling with extracellularly added horseradish peroxidase (HRP). In addition, a small number of synaptic vesicles entrapped HRP under these conditions. After repolarization, the number of HRP loaded endosome-like structures decreased. Simultaneously, a strong increase in amount of HRP-loaded small vesicles did occur. These results indicate that during sub-second depolarization, synaptic vesicles were rapidly recruited from the reserve pool to replenish the releasable pool, whereas prolonged depolarization (s-min) induced local endocytosis in at least two ways, i.e. either directly as vesicles or via endosome-like organelles from which synaptic vesicles were reformed. PMID- 11784711 TI - Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. AB - Extracorporeal shock wave (ESW) is an alternative non-invasive method for the promotion of bone growth and tendon repair. In an animal model, we have reported that ESW promoted bone marrow osteoprogenitor growth through transforming growth factor-beta1 induction. We have further explored the mechanism for the ESW promotion of osteogenesis. Results showed that an optimal ESW treatment at 0.16 mJ/mm(2) for 500 impulses rapidly induced a higher O(2)(-) and ONOO(-) production associated with a decrease of nitric oxide level in 1 h, and induced a higher transforming growth factor-beta1 production in 24 h, and a higher colony-forming units-osteoprogenitor formation in 12 days. The colony-forming units osteoprogenitor colonies revealed positive staining of bone alkaline phosphatase and turned into bone nodules in 21 days. Early scavenging of O(2)(-) but not Ca(2+), H(2)O(2), or prostaglandin E(2) suppressed osteoprogenitor cell growth and maturation. Scavenging of O(2)(-) by superoxide dismutase raised the nitric oxide level back to the basal level and suppressed ESW-promoted osteoprogenitor cell growth, whereas inhibition of ONOO(-) by urate or NO by N-nitro-l-arginine methyl ester did not affect ESW promotion of osteogenesis, indicating that O(2)( ) acted as an early signal for ESW-induced cell growth. Further studies demonstrated that ESW induced ERK activation, and blockage of O(2)(-) production or inhibition of tyrosine kinase, but not protein kinase A and C inhibitors, suppressed ESW-induced ERK activation. In support that O(2)(-) mediated the ESW induced ERK activation and osteogenic differentiation, we further demonstrated that scavenging of O(2)(-) by superoxide dismutase and inhibition of ERK activation by PD98059 decreased specific osteogenic transcription factor, core binding factor A1 activation, and decreased osteocalcin expression. Taken together, we showed that ESW-induced O(2)(-) production followed by tyrosine kinase-mediated ERK activation and core binding factor A1 activation resulted in osteogenic cell growth and maturation. Thus, an appropriate modulation of redox reaction by ESW may have some positive effect on the bone regeneration. PMID- 11784712 TI - Cloning and characterization of a family of proteins associated with Mpl. AB - Thrombopoietin (TPO) controls the formation of megakaryocytes and platelets from hematopoietic stem cells via activation of the c-Mpl receptor and multiple downstream signal transduction pathways. We used two-hybrid screening to identify new proteins that interacted with the cytoplasmic domain of Mpl, and we found a new family of proteins designated A2D (for Ataxin-2 Domain protein). The A2D are 130-kDa proteins that have three regions similar to those of Ataxin-2, the gene product causing familial type 2 spinocerebellar ataxia. A2D has several isoforms with different C-terminal domains, all produced from a single gene by alternative splicing. Northern blotting indicated that the A2D gene is widely expressed in immortalized cell lines and hematopoietic and fetal tissues. A2D proteins were constitutively associated with Mpl in vivo in human hematopoietic UT7 cells. TPO also caused the release of A2D from the activated receptor, and the phosphorylation of A2D on tyrosines residues was dependent on the Mpl C-terminal domain. Finally, A2D bound to the unstimulated erythropoietin receptor, whereas erythropoietin caused dissociation from the erythropoietin receptor, suggesting that A2D proteins are new components of the cytokine signaling system. PMID- 11784713 TI - Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin-8 in human brain microvascular endothelial cells. AB - Hypoxia, a strong inducer for vascular endothelial growth factor (VEGF)/vascular permeable factor (VPF) expression, regulates leukocyte infiltration through the up-regulation of adhesion molecules and chemokine release. To determine whether VEGF/VPF is directly involved in chemokine secretion, we analyzed its effects on chemokine expression in human brain microvascular endothelial cells (HBMECs) by using a human cytokine cDNA array kit. Cytokine array analysis revealed a significant increase in expression of monocyte chemoattractant protein-1 and the chemokine receptor CXCR4 in HBMECs, a result similar to that described previously in other endothelial cells. Interestingly, we also observed that VEGF/VPF induced interleukin-8 (IL-8) expression in HBMECs and that IL-8 mRNA was maximal after 1 h of VEGF/VPF treatment of the cells. Enzyme-linked immunosorbent assay data and immunoprecipitation analysis revealed that although VEGF/VPF induced IL-8 expression at the translational level in HBMECs, basic fibroblast growth factor failed to induce this protein expression within 12 h. VEGF/VPF increased IL-8 production in HBMECs through activation of nuclear factor-KB via calcium and phosphatidylinositol 3-kinase pathways, whereas the ERK pathway was not involved in this process. Supernatants of the VEGF/VPF-treated HBMECs significantly increased neutrophil migration across the HBMEC monolayer compared with those of the untreated control. Furthermore, addition of anti-IL-8 antibody blocked this increased migration, indicating that VEGF/VPF induced the functional expression of IL-8 protein in HBMECs. Taken together, these data demonstrate for the first time that VEGF/VPF induces IL-8 expression in HBMECs and contributes to leukocyte infiltration through the expression of chemokines, such as IL-8, in endothelial cells. PMID- 11784714 TI - Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase activating polypeptides. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that acts through G protein-coupled receptors, exerts neuroprotective effects upon many neuronal populations. However, the intracellular signaling mechanisms that account for PACAP's trophic effects are not well characterized. Here we have tested the possibility that PACAP uses neurotrophin signaling pathways. We have found that PACAP treatment resulted in an increase in TrkA tyrosine kinase activity in PC12 cells and TrkB activity in hippocampal neurons. The activation of TrkA receptors by PACAP required at least 1 h of treatment and did not involve binding to nerve growth factor. Moreover, PACAP induced an increase in activated Akt through a Trk-dependent mechanism that resulted in increased cell survival after trophic factor withdrawal. The increases in Trk and Akt were blocked by K252a, an inhibitor of Trk receptor activity. In addition, transactivation of TrkA receptors by PACAP could be inhibited with PP1, an inhibitor of Src family kinases or BAPTA/AM, (1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester), an intracellular calcium chelator. Therefore, PACAP can exert trophic effects through a mechanism involving Trk receptors and utilization of tyrosine kinase signaling. This ability may explain several neuroprotective actions of PACAP upon neuronal populations after injury, nerve lesion, or neurotrophin deprivation. PMID- 11784715 TI - Hepatocyte growth factor induces ERK-dependent paxillin phosphorylation and regulates paxillin-focal adhesion kinase association. AB - Hepatocyte growth factor (HGF) modulates cell adhesion, migration, and branching morphogenesis in cultured epithelial cells, events that require regulation of cell-matrix interactions. Using mIMCD-3 epithelial cells, we studied the effect of HGF on the focal adhesion proteins, focal adhesion kinase (FAK) and paxillin and their association. HGF was found to increase the tyrosine phosphorylation of paxillin and to a lesser degree FAK. In addition, HGF induced association of paxillin and activated ERK, correlating with a gel retardation of paxillin that was prevented with the ERK inhibitor U0126. The ability of activated ERK to phosphorylate and induce gel retardation of paxillin was confirmed in vitro in both full-length and amino-terminal paxillin. Several potential ERK phosphorylation sites in paxillin flank the paxillin-FAK association domains, so the ability of HGF to regulate paxillin-FAK association was examined. HGF induced an increase in paxillin-FAK association that was inhibited by pretreatment with U0126 and reproduced by in vitro phosphorylation of paxillin with ERK. The prevention of the FAK-paxillin association with U0126 correlated with an inhibition of the HGF-mediated FAK tyrosine phosphorylation and inhibition of HGF dependent cell spreading and adhesion. An examination of cellular localization of FAK and paxillin demonstrated that HGF caused a condensation of focal adhesion complexes at the leading edges of cell processes and FAK-paxillin co-localization in these large complexes. Thus, these data suggest that HGF can induce serine/threonine phosphorylation of paxillin most probably mediated directly by ERK, resulting in the recruitment and activation of FAK and subsequent enhancement of cell spreading and adhesion. PMID- 11784716 TI - Transforming growth factor beta 1 induces proliferation in colon carcinoma cells by Ras-dependent, smad-independent down-regulation of p21cip1. AB - Transforming growth factor beta1 (TGFbeta1) can act as a tumor suppressor or a tumor promoter depending on the characteristics of the malignant cell. We recently demonstrated that colon carcinoma cells transfected with oncogenic cellular K-rasV12, but not oncogenic cellular H-rasV12, switched from TGFbeta1 insensitive to TGFbeta1-growth-stimulated and also became more invasive (Yan, Z., Deng, X., and Friedman, E. (2001) J. Biol. Chem. 276, 1555-1563). We now demonstrate that TGFbeta1 growth stimulation of colon carcinoma cells is Ras dependent and smad-independent. In U9 colon carcinoma cells, which are responsive to TGFbeta1 by growth stimulation, a truncating mutation at Gln-311 was found in the smad4 gene. Very little smad4 protein was detected in these cells. Loss of smad4 protein was confirmed by functional studies. In U9 cells co-transfected wild-type smad4, but not mutant smad4, mediated response of the 3TP-lux and pSBE promoter reporter constructs to TGFbeta1. Proliferation initiated by TGFbeta1 in U9 cells required Ras-mediated down-regulation of p21cip1 protein. Less p21cip1 was associated with cdk2 small middle dotcyclin complexes in TGFbeta1-treated U9 cells, and the cdk2 complexes had increased kinase activity. Elevation of p21cip1 levels diminished proliferative response to TGFbeta1. U9 cells expressing DN N17ras neither proliferated in response to TGFbeta1 nor down-regulated the cdk inhibitor p21cip1, and TGFbeta1 activation of 3TP-lux in U9 cells was inhibited by DN-N17ras in a dose-dependent manner. TGFbeta1 also decreased p21cip1 levels and stimulated proliferation in SW480 cells, which express mutant K-Ras but no smad4 protein. TGFbeta1 did not activate or inhibit the p21cip1 promoter construct in U9 cells even in the presence of co-transfected smad4, or alter p21cip1 mRNA levels. Thus the decrease in p21cip1 levels was mediated by a TGFbeta-initiated Ras-dependent, but smad-independent post-transcriptional mechanism. PMID- 11784717 TI - Nitric oxide and cGMP-dependent protein kinase regulation of glucose-mediated thrombospondin 1-dependent transforming growth factor-beta activation in mesangial cells. AB - Excessive transforming growth factor-beta (TGF-beta) activity in hyperglycemia contributes to the development of diabetic nephropathy. Glucose stimulation of TGF-beta activity and matrix synthesis are dependent on autocrine thrombospondin 1 (TSP1) to convert latent TGF-beta to its biologically active form. The mechanisms by which glucose regulates TSP1 are not known. High glucose inhibits nitric oxide (NO) bioavailability and decreased NO increases TGF-beta activity and extracellular matrix accumulation. Yet, the impact of NO signaling on TSP1 activation of TGF-beta is unknown. We tested the role of NO signaling in the regulation of TSP1 expression and TSP1-dependent TGF-beta activity in rat mesangial cells exposed to high glucose. On exposure to 30 mm glucose, NO accumulation in the conditioned media and intracellular cGMP levels were significantly decreased. The addition of an NO donor prevented the glucose dependent increase in TSP1 mRNA, protein, and TGF-beta bioactivity. The effects of the NO donor were blocked by ODQ (a soluble guanylate cyclase inhibitor) or Rp 8-pCPT-cGMPS (an inhibitor of cGMP-dependent protein kinase). These effects of high glucose were also reversed by the nitric-oxide synthase cofactor tetrahyrobiopterin (BH(4)). These results show that high glucose mediates increases in TSP1 expression and TSP1-dependent TGF-beta bioactivity through down modulation of NO-cGMP-dependent protein kinase signaling. PMID- 11784718 TI - High glucose-altered gene expression in mesangial cells. Actin-regulatory protein gene expression is triggered by oxidative stress and cytoskeletal disassembly. AB - High extracellular glucose plays a pivotal role in the pathophysiology of diabetic nephropathy. Here we report 200 genes, identified using suppression subtractive hybridization, that are differentially expressed when human mesangial cells are propagated in high ambient glucose in vitro. The major functional classes of genes identified included modulators and products of extracellular matrix protein metabolism, regulators of cell growth and turnover, and a cohort of actin cytoskeleton regulatory proteins. Actin cytoskeletal disassembly is a prominent feature of diabetic nephropathy. The induction of actin cytoskeleton regulatory gene expression by high glucose was attenuated by the inhibitor of reactive oxygen species generation, carbonyl cyanide m-chlorophenylhydrazone but not by the protein kinase C inhibitor GF 109203X and was not mimicked by the addition of transforming growth factor beta. Enhanced expression of actin cytoskeleton regulatory genes was also observed following disruption of the mesangial cell actin cytoskeleton by cytochalasin D. In aggregate, these results suggest that the induction of genes encoding actin cytoskeleton regulatory proteins (a) is a prominent component of the mesangial cell transcriptomic response in diabetic nephropathy and (b) is dependent on oxidative stress, is independent of protein kinase C and transforming growth factor-beta, and represents an adaptive response to actin cytoskeleton disassembly. PMID- 11784719 TI - Insulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells. AB - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) can stimulate apoptosis and inhibit cell proliferation directly and independently of binding IGFs or indirectly by forming complexes with IGF-I and IGF-II that prevent them from activating the IGF-I receptor to stimulate cell survival and proliferation. To date, IGF-independent actions only have been demonstrated in a limited number of cells that do not synthesize or respond to IGFs. To assess the general importance of IGF-independent mechanisms, we have generated human IGFBP-3 mutants that cannot bind IGF-I or IGF-II by substituting alanine for six residues in the proposed IGF binding site, Ile(56)/Tyr(57)/Arg(75)/Leu(77)/Leu(80)/Leu(81), and expressing the 6m-hIGFBP-3 mutant construct in Chinese hamster ovary cells. Binding of both IGF-I and IGF-II to 6m-hIGFBP-3 was reduced >80-fold. The nonbinding 6m-hIGFBP-3 mutant still was able to inhibit DNA synthesis in a mink lung epithelial cell line in which inhibition by wild-type hIGFBP-3 previously had been shown to be exclusively IGF-independent. 6m-hIGFBP-3 only can act by IGF independent mechanisms since it is unable to form complexes with the IGFs that inhibit their action. We next compared the ability of wild-type and 6m-hIGFBP-3 to stimulate apoptosis in serum-deprived PC-3 human prostate cancer cells. PC-3 cells are known to synthesize and respond to IGF-II, so that IGFBP-3 could potentially act by either IGF-dependent or IGF-independent mechanisms. In fact, 6m-hIGFBP-3 stimulated PC-3 cell death and stimulated apoptosis-induced DNA fragmentation to the same extent and with the same concentration dependence as wild-type hIGFBP-3. These results indicate that IGF-independent mechanisms are major contributors to IGFBP-3-induced apoptosis in PC-3 cells and may play a wider role in the antiproliferative and antitumorigenic actions of IGFBP-3. PMID- 11784720 TI - Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29. AB - The activity of cyclin-dependent kinase-5 (Cdk5) is tightly regulated by binding of its neuronal activators p35 and p39. Upon neurotoxic insults, p35 is cleaved to p25 by the Ca(2+)-dependent protease calpain. p25 is accumulated in ischemic brains and in brains of patients with Alzheimer's disease. p25 deregulates Cdk5 activity by causing prolonged activation and mislocalization of Cdk5. It is unknown whether p39, which is expressed throughout the adult rat brain, is cleaved by calpain, and whether this contributes to deregulation of Cdk5. Here, we show that calpain cleaved p39 in vitro, resulting in generation of a C terminal p29 fragment. In vivo, p29 was generated in ischemic brain concomitant with increased calpain activity. In fresh brain lysates, generation of p29 was Ca(2+)-dependent, and calpain inhibitors abolished p29 production. The Ca(2+) ionophore ionomycin and the excitotoxin glutamate induced production of p29 in cultures of cortical neurons in a calpain-dependent manner. Like p25, p29 was more stable than p39 and caused redistribution of Cdk5 in cortical neurons. Our data suggest that neurotoxic insults lead to calpain-mediated conversion of p39 to p29, which might contribute to deregulation of Cdk5. PMID- 11784721 TI - Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity. AB - Insulin inhibits the expression of the hepatic insulin-like growth factor-binding protein-1 (IGFBP-1) and glucose-6-phosphatase (G6Pase) genes. The signaling pathway that mediates these events requires the activation of phosphatidylinositol 3-kinase, whereas transfection studies have suggested an involvement of Akt (protein kinase B) and FKHR, a transcription factor regulated by Akt. We now demonstrate that insulin repression of endogenous IGFBP-1 gene transcription was blocked by rapamycin or by amino acid starvation. Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin, whereas amino acid depletion prevented insulin induction of these signaling molecules. Importantly, we demonstrate that insulin regulation of the thymine-rich insulin response element of the IGFBP-1 promoter was also inhibited by rapamycin. However, sustained activation of S6K1 did not repress this promoter. In addition, rapamycin did not affect insulin regulation of G6Pase expression or Akt activation. We propose that these observations indicate that an mTOR-dependent, but S6K-independent mechanism regulates the suppression of IGFBP-1 (but not G6Pase) gene expression by insulin. Therefore, although the insulin-responsive sequence of the G6Pase gene promoter is related to that of the IGFBP-1 promoter, the signaling pathways that mediate suppression of these genes are distinct. PMID- 11784722 TI - PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. AB - Phosphatidylinositol 3-kinase is activated by vascular endothelial growth factor (VEGF), and many of the angiogenic cellular responses of VEGF are regulated by the lipid products of phosphatidylinositol 3-kinase. The tumor suppressor PTEN has been shown to down-regulate phosphatidylinositol 3-kinase signaling, yet the effects of PTEN on VEGF-mediated signaling and angiogenesis are unknown. Inhibition of endogenous PTEN in cultured endothelial cells by adenovirus mediated overexpression of a dominant negative PTEN mutant (PTEN-C/S) enhanced VEGF-mediated Akt phosphorylation, and this effect correlated with decreases in caspase-3 cleavage, caspase-3 activity, and DNA degradation after induction of apoptosis with tumor necrosis factor-alpha. Overexpression of PTEN-C/S also enhanced VEGF-mediated endothelial cell proliferation and migration. In contrast, overexpression of wild-type PTEN inhibited the anti-apoptotic, proliferative, and chemotactic effects of VEGF. Moreover, PTEN-C/S increased the length of vascular sprouts in the rat aortic ring assay and modulated VEGF-mediated tube formation in an in vitro angiogenesis assay, whereas PTEN-wild type inhibited these effects. Taken together, these findings demonstrate that PTEN potently modulates VEGF-mediated signaling and function and that PTEN is a viable target in therapeutic approaches to promote or inhibit angiogenesis. PMID- 11784723 TI - A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting. AB - Intercellular adhesion molecule 3 (ICAM-3) is a leukocyte-specific receptor involved in primary immune responses. We have investigated the interaction between ICAM-3 and ezrin/radixin/moesin (ERM) proteins and its role in LFA-1 induced cell-cell interactions and membrane positioning of ICAM-3 in polarized migrating lymphocytes. Protein-protein binding assays demonstrated a phosphatidylinositol 4,5-bisphosphate-induced association between ICAM-3 and the amino-terminal domain of ERM proteins. This interaction was not essential for the binding of ICAM-3 to LFA-1. Dynamic fluorescence videomicroscopy studies of cells demonstrated that moesin and ICAM-3 coordinately redistribute on the plasma membrane during lymphocyte migration. Furthermore, overexpression of the amino terminal domain of moesin, which lacks the consensus moesin actin-binding site, caused the subcellular mislocalization of ICAM-3. A CD4 chimerical protein containing the cytoplasmic tail of ICAM-3 was targeted to the trailing edge. Point mutation of Ser(487), Ser(489), and Ser(496) to alanine in the juxtamembrane region of ICAM-3 significantly impaired both ERM binding and polarization of ICAM-3. ERM-directed polarization of ICAM-3 was also impaired by phosphorylation-like mutation of Ser(487) and Ser(489), but not of Ser(496). Our results underscore the key role of specific serine residues within the cytoplasmic region of ICAM-3 for its ERM-directed positioning at the trailing edge of motile lymphocytes. PMID- 11784724 TI - Molecular characterization of a second copy of holocarboxylase synthetase gene (hcs2) in Arabidopsis thaliana. AB - Holocarboxylase synthetase (HCS), catalyzing the covalent attachment of biotin, is ubiquitously represented in living organisms. Indeed, the biotinylation is a post-translational modification that allows the transformation of inactive biotin dependent carboxylases, which are committed in fundamental metabolisms such as fatty acid synthesis, into their active holo form. Among other living organisms, plants present a peculiarly complex situation. In pea, HCS activity has been detected in three subcellular compartments and the systematic sequencing of the Arabidopsis genome revealed the occurrence of two hcs genes (hcs1 and hcs2). Hcs1 gene product had been previously characterized at molecular and biochemical levels. Here, by PCR amplification, we cloned an hcs2 cDNA from Arabidopsis thaliana (Ws ecotype) mRNA. We observed the occurrence of multiple cDNA forms which resulted from the alternative splicing of hcs2 mRNA. Furthermore, we evidenced a nucleotide polymorphism at the hcs2 gene within the Ws ecotype, which affected splicing of hcs2 mRNA. This contrasted sharply with the situation at hcs1 locus. However, this polymorphism had no apparent effect on total HCS activity in planta. Finally, hcs2 mRNAs were found 4-fold less abundant than hcs1 mRNA and the most abundant hcs2 mRNA spliced variant should code for a truncated protein. We discuss the possible role of such a multiplicity of putative HCS proteins in plants and discuss the involvement of each of hcs genes in the correct realization of biotinylation. PMID- 11784725 TI - Modifications of vestibular responses of individual reticulospinal neurons in lamprey caused by unilateral labyrinthectomy. AB - A postural control system in the lamprey is driven by vestibular input and maintains the dorsal-side-up orientation of the animal during swimming. After a unilateral labyrinthectomy (UL), the lamprey continuously rolls toward the damaged side. Normally, a recovery of postural equilibrium ("vestibular compensation") takes about 1 mo. However, illumination of the eye contralateral to UL results in an immediate and reversible restoration of equilibrium. Here we used eye illumination as a tool to examine a functional recovery of the postural network. Important elements of this network are the reticulospinal (RS) neurons, which are driven by vestibular input and transmit commands for postural corrections to the spinal cord. In this study, we characterized modifications of the vestibular responses in individual RS neurons caused by UL and the effect exerted on these responses by eye illumination. The activity of RS neurons was recorded from their axons in the spinal cord by chronically implanted electrodes, and spikes in individual axons were extracted from the population activity signals. The same neurons were recorded both before and after UL. Vestibular stimulation (rotation in the roll plane through 360 degrees ) and eye illumination were performed in quiescent animals. It was found that the vestibular responses on the UL-side changed only slightly, whereas the responses on the opposite side disappeared almost completely. This asymmetry in the bilateral activity of RS neurons is the most likely cause for the loss of equilibrium in UL animals. Illumination of the eye contralateral to UL resulted, first, in a restoration of vestibular responses in the neurons inactivated by UL and in an appearance of vestibular responses in some other neurons that did not respond to vestibular input before UL. These responses had directional sensitivity and zones of spatial sensitivity similar to those observed before UL. However, their magnitude was smaller than before UL. Second, the eye illumination caused a reduction of the magnitude of vestibular responses on the UL side. These two factors tend to restore symmetry in bilateral activity of RS neurons, which is the most likely cause for the recovery of equilibrium in the swimming UL lamprey. Results of this study are discussed in relation to the model of the roll control system proposed in our previous studies as well as in relation to the vestibular compensation. PMID- 11784726 TI - Giant miniature EPSCs at the hippocampal mossy fiber to CA3 pyramidal cell synapse are monoquantal. AB - The mechanisms generating giant miniature excitatory postsynaptic currents (mEPSCs) were investigated at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse in vitro. These giant mEPSCs have peak amplitudes as large as 1,700 pA (13.6 nS) with a mean maximal mEPSC amplitude of 366 +/- 20 pA (mean +/- SD; 5 nS; n = 25 cells). This is compared with maximal mEPSC amplitudes of <100 pA typically observed at other cortical synapses. We tested the hypothesis that giant mEPSCs are due to synchronized release of multiple vesicles across the release sites of single MF boutons by directly inducing vesicular release using secretagogues. If giant mEPSCs result from simultaneous multivesicular release, then secretagogues should increase the frequency of small mEPSCs selectively. We found that hypertonic sucrose and spermine increased the frequency of both small and giant mEPSCs. The peptide toxin secretagogues alpha-latrotoxin and pardaxin failed to increase the frequency of giant mEPSCs, but the possible lack of tissue penetration of the toxins make these results equivocal. Because a multiquantal release mechanism is likely to be mediated by a spontaneous increase in presynaptic calcium concentration, a monoquantal mechanism is further supported by results that giant mEPSCs were not affected by manipulations of extracellular or intracellular calcium concentrations. In addition, reducing the temperature of the bath to 15 degrees C failed to desynchronize the rising phases of giant mEPSCs. Together these data suggest that the giant mEPSCs are generated via a monovesicular mechanism. Three-dimensional analysis through serial electron microscopy of the MF boutons revealed large clear vesicles (50 to 160 nm diam) docked presynaptically at the MF synapse in sufficient numbers to account for the amplitude and frequency of giant mEPSCs recorded electrophysiologically. It is concluded that release of the contents of a single large clear vesicle generates giant mEPSCs at the MF to CA3 pyramidal cell synapse. PMID- 11784727 TI - Heterogeneous intrinsic firing properties of vertebrate retinal ganglion cells. AB - Retinal ganglion cells (RGCs) use their characteristic firing patterns to encode various aspects of visual information and carry them to the brain. It has been thought that the firing pattern of an RGC's light response is determined primarily by the time course and spatiotemporal interaction of the synaptic inputs. However, it is unclear whether there is a difference in intrinsic firing properties among RGCs that could contribute to the cell-to-cell distinction of the light response firing pattern. We investigated the intrinsic firing properties of isolated goldfish RGCs, minimizing cytoplasmic disturbance with a perforated-patch, whole-cell recording technique. In response to a 1-s depolarizing current step, the majority of the examined RGCs (n = 84) displayed sustained firing that lasted over 800 ms (n = 24; tonic RGCs) or transient firing accommodated within 200 ms of the step onset (n = 47; phasic RGCs). Tonic and phasic RGCs also differed in their firing frequency-current intensity dynamics. There was a significant difference in the soma sizes of phasic and tonic RGCs, indicating that some parts of these groups originate from distinct morphological subtypes. In the presence of extracellular Ba(2+) (1 mM), phasic RGCs displayed sustained firing and firing frequency-current intensity dynamics similar to those of tonic RGCs. Thus a Ba(2+)-sensitive ion current (I(Ba-s)) underlies the firing characteristics of phasic RGCs. Under voltage-clamp conditions, I(Ba-s) was identified as a low-threshold, noninactivating voltage-dependent K(+) current. Because of its slow kinetics (time constant of activation, approximately 100 ms), I(Ba-s) may confer a gradually increasing hyperpolarizing driving force during maintained excitatory stimulus, which eventually would result in firing accommodation. These findings suggest that RGCs have heterogeneous intrinsic firing properties that could aid synaptic inputs in shaping light responses. PMID- 11784728 TI - Temporal properties of the mouse cone electroretinogram. AB - To determine the temporal response characteristics of the mouse cone electroretinogram (ERG), we recorded responses to high contrast sinusoidal stimuli ranging from 2 to 52 Hz. The largest response amplitudes obtained from wild-type (WT) mice occurred at stimulus frequencies below 10 Hz, and cone ERG amplitude declined progressively with increasing stimulus frequency above that level. In comparison, human responses recorded under the same stimulus and recording conditions displayed maximal responses to stimulus frequencies near 4 and 40 Hz, and a pronounced dip at 12 Hz. Responses were also obtained from nob (no b-wave) mice, which lack ERG contributions from depolarizing bipolar cells (DBCs). At low temporal frequencies, nob cone ERGs were smaller than those of WT mice and had a different waveform. As temporal frequency increased, nob and WT responses became more similar and came into register at the highest temporal frequencies. To evaluate the contribution of the DBC pathway to the mouse cone ERG, nob responses were vector-subtracted from those of WT mice. The derived DBC response was maximal at low stimulus frequencies and fell sharply as stimulus frequency increased. These results indicate that the mouse cone ERG is more linear than the primate response and that the temporal response of the mouse outer retina is tuned to much lower frequencies than that of primate. PMID- 11784729 TI - Interneuronal and peptidergic control of motor pattern switching in Aplysia. AB - It has been proposed that a choice of specific behaviors can be mediated either by activation of behavior-specific higher order neurons or by distinct combinations of such neurons in different behaviors. We examined the role that two higher order neurons, CBI-2 and CBI-3, play in the selection of motor programs that correspond to ingestion and egestion, two stimulus-dependent behaviors that are generated by a single central pattern generator (CPG) of Aplysia. We found that CBI-2 could evoke either ingestive, egestive, or ambiguous motor programs depending on the regime of stimulation. When CBI-2 recruited CBI-3 firing via electrical coupling, the motor program tended to be ingestive. In the absence of CBI-3 activation, the program was usually egestive. When CBI-2 was stimulated to produce ingestive programs, hyperpolarization of CBI-3 converted the programs to egestive or ambiguous. When CBI-2 was stimulated to produce egestive or ambiguous programs, co-stimulation of CBI-3 converted them into ingestive. These findings are consistent with the idea that combinatorial commands are responsible for the choice of specific behaviors. Additional support for this view comes from the observations that appropriate stimulus conditions exist both for activation of CBI-2 together with CBI-3, and for activation of CBI 2 without a concomitant activation of CBI-3. The ability of CBI-3 to convert egestive and ambiguous programs into ingestive ones was mimicked by application of APGWamide, a neuropeptide that we have detected in CBI-3 by immunostaining. Thus combinatorial actions of higher order neurons that underlie pattern selection may involve the use of modulators released by specific higher order neurons. PMID- 11784730 TI - Conditions sufficient for nonsynaptic epileptogenesis in the CA1 region of hippocampal slices. AB - Nonsynaptic mechanisms exert a powerful influence on seizure threshold. It is well-established that nonsynaptic epileptiform activity can be induced in hippocampal slices by reducing extracellular Ca(2+) concentration. We show here that nonsynaptic epileptiform activity can be readily induced in vitro in normal (2 mM) Ca(2+) levels. Those conditions sufficient for nonsynaptic epileptogenesis in the CA1 region were determined by pharmacologically mimicking the effects of Ca(2+) reduction in normal Ca(2+) levels. Increasing neuronal excitability, by removing extracellular Mg(2+) and increasing extracellular K(+) (6-15 mM), induced epileptiform activity that was suppressed by postsynaptic receptor antagonists [D-(-)-2-amino-5-phosphonopentanoic acid, picrotoxin, and 6,7 dinitroquinoxaline-2,3-dione] and was therefore synaptic in nature. Similarly, epileptiform activity induced when neuronal excitability was increased in the presence of K(Ca) antagonists (verruculogen, charybdotoxin, norepinephrine, tetraethylammonium salt, and Ba(2+)) was found to be synaptic in nature. Decreases in osmolarity also failed to induce nonsynaptic epileptiform activity in the CA1 region. However, increasing neuronal excitability (by removing extracellular Mg(2+) and increasing extracellular K(+)) in the presence of Cd(2+), a nonselective Ca(2+) channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity in vitro. Both novel models were characterized using intracellular and ion-selective electrodes. The results of this study suggest that reducing extracellular Ca(2+) facilitates bursting by increasing neuronal excitability and inhibiting Ca(2+) influx, which might, in turn, enhance a persistent sodium conductance. Furthermore, these data show that nonsynaptic mechanisms can contribute to epileptiform activity in normal Ca(2+) levels. PMID- 11784731 TI - Functional organization of the pallid bat auditory cortex: emphasis on binaural organization. AB - This report maps the organization of the primary auditory cortex of the pallid bat in terms of frequency tuning, selectivity for behaviorally relevant sounds, and interaural intensity difference (IID) sensitivity. The pallid bat is unusual in that it localizes terrestrial prey by passively listening to prey-generated noise transients (1-20 kHz), while reserving high-frequency (<30 kHz) echolocation for obstacle avoidance. The functional organization of its auditory cortex reflects the need for specializations in echolocation and passive sound localization. Best frequencies were arranged tonotopically with a general increase in the caudolateral to rostromedial direction. Frequencies between 24 and 32 kHz were under-represented, resulting in hypertrophy of frequencies relevant for prey localization and echolocation. Most neurons (83%) tuned <30 kHz responded preferentially to broadband or band-pass noise over single tones. Most neurons (62%) tuned >30 kHz responded selectively or exclusively to the 60- to 30 kHz downward frequency-modulated (FM) sweep used for echolocation. Within the low frequency region, neurons were placed in two groups that occurred in two separate clusters: those selective for low- or high-frequency band-pass noise and suppressed by broadband noise, and neurons that showed no preference for band pass noise over broadband noise. Neurons were organized in homogeneous clusters with respect to their binaural response properties. The distribution of binaural properties differed in the noise- and FM sweep-preferring regions, suggesting task-dependent differences in binaural processing. The low-frequency region was dominated by a large cluster of binaurally inhibited neurons with a smaller cluster of neurons with mixed binaural interactions. The FM sweep-selective region was dominated by neurons with mixed binaural interactions or monaural neurons. Finally, this report describes a cortical substrate for systematic representation of a spatial cue, IIDs, in the low-frequency region. This substrate may underlie a population code for sound localization based on a systematic shift in the distribution of activity across the cortex with sound source location. PMID- 11784732 TI - Differential role of KIR channel and Na(+)/K(+)-pump in the regulation of extracellular K(+) in rat hippocampus. AB - Little information is available on the specific roles of different cellular mechanisms involved in extracellular K(+) homeostasis during neuronal activity in situ. These studies have been hampered by the lack of an adequate experimental paradigm able to separate K(+)-buffering activity from the superimposed extrusion of K(+) from variably active neurons. We have devised a new protocol that allows for such an analysis. We used paired field- and K(+)-selective microelectrode recordings from CA3 stratum pyramidale during maximal Schaffer collateral stimulation in the presence of excitatory synapse blockade to evoke purely antidromic spikes in CA3. Under these conditions of controlled neuronal firing, we studied the [K(+)]o baseline during 0.05 Hz stimulation, and the accumulation and rate of recovery of extracellular K(+) at higher frequency stimulation (1-3 Hz). In the first set of experiments, we showed that neuronal hyperpolarization by extracellular application of ZD7288 (11 microM), a selective blocker of neuronal I(h) currents, does not affect the dynamics of extracellular K(+). This indicates that the K(+) dynamics evoked by controlled pyramidal cell firing do not depend on neuronal membrane potential, but only on the balance between K(+) extruded by firing neurons and K(+) buffered by neuronal and glial mechanisms. In the second set of experiments, we showed that di-hydro-ouabain (5 microM), a selective blocker of the Na(+)/K(+)-pump, yields an elevation of baseline [K(+)]o and abolishes the K(+) recovery during higher frequency stimulation and its undershoot during the ensuing period. In the third set of experiments, we showed that Ba(2+) (200 microM), a selective blocker of inwardly rectifying K(+) channels (KIR), does not affect the posttetanus rate of recovery of [K(+)]o, nor does it affect the rate of K(+) recovery during high-frequency stimulation. It does, however, cause an elevation of baseline [K(+)]o and an increase in the amplitude of the ensuing undershoot. We show for the first time that it is possible to differentiate the specific roles of Na(+)/K(+)-pump and KIR channels in buffering extracellular K(+). Neuronal and glial Na(+)/K(+)-pumps are involved in setting baseline [K(+)]o levels, determining the rate of its recovery during sustained high-frequency firing, and determining its postactivity undershoot. Conversely, glial KIR channels are involved in the regulation of baseline levels of K(+), and in decreasing the amplitude of the postactivity [K(+)]o undershoot, but do not affect the rate of K(+) clearance during neuronal firing. The results presented provide new insights into the specific physiological role of glial KIR channels in extracellular K(+) homeostasis. PMID- 11784733 TI - Processing of nociceptive mechanical and thermal information in central amygdala neurons with knee-joint input. AB - Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. In 46 anesthetized rats, extracellular single-unit recordings were made from 119 central amygdala neurons that were activated orthodromically by electrical stimulation in the lateral pontine parabrachial area and were tested for receptive fields in the knee joints. Responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Receptive-field sizes and thresholds were mapped and stimulus-response functions constructed. Neurons in the central nucleus of the amygdala with excitatory input from the knee joint (n = 62) typically had large symmetrical receptive fields in both hindlimbs or in all four extremities and responded exclusively or preferentially to noxious mechanical stimulation of deep tissue (n = 58). Noxious mechanical stimulation of the skin excited 30 of these neurons; noxious heat activated 21 neurons. Stimulus-response data were best fitted by a sigmoid nonlinear regression model rather than by a monotonically increasing linear function. Another 15 neurons were inhibited by noxious mechanical stimulation of the knee joint and other deep tissue. Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain. PMID- 11784734 TI - Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons. AB - Short-lasting application (10 min) of tachykinin neuropeptides evokes long lasting (>24 h) modulation of N-methyl-D-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist D-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output. PMID- 11784735 TI - Functional role of auditory cortex in frequency processing and pitch perception. AB - Microelectrode studies in nonhuman primates and other mammals have demonstrated that many neurons in auditory cortex are excited by pure tone stimulation only when the tone's frequency lies within a narrow range of the audible spectrum. However, the effects of auditory cortex lesions in animals and humans have been interpreted as evidence against the notion that neuronal frequency selectivity is functionally relevant to frequency discrimination. Here we report psychophysical and anatomical evidence in favor of the hypothesis that fine-grained frequency resolution at the perceptual level relies on neuronal frequency selectivity in auditory cortex. An adaptive procedure was used to measure difference thresholds for pure tone frequency discrimination in five humans with focal brain lesions and eight normal controls. Only the patient with bilateral lesions of primary auditory cortex and surrounding areas showed markedly elevated frequency difference thresholds: Weber fractions for frequency direction discrimination ("higher"-"lower" pitch judgments) were about eightfold higher than Weber fractions measured in patients with unilateral lesions of auditory cortex, auditory midbrain, or dorsolateral frontal cortex; Weber fractions for frequency change discrimination ("same"-"different" pitch judgments) were about seven times higher. In contrast, pure-tone detection thresholds, difference thresholds for pure tone duration discrimination centered at 500 ms, difference thresholds for vibrotactile intensity discrimination, and judgments of visual line orientation were within normal limits or only mildly impaired following bilateral auditory cortex lesions. In light of current knowledge about the physiology and anatomy of primate auditory cortex and a review of previous lesion studies, we interpret the present results as evidence that fine-grained frequency processing at the perceptual level relies on the integrity of finely tuned neurons in auditory cortex. PMID- 11784736 TI - Coding of temporal information by activity-dependent synapses. AB - Synaptic transmission in the neocortex is dynamic, such that the magnitude of the postsynaptic response changes with the history of the presynaptic activity. Therefore each response carries information about the temporal structure of the preceding presynaptic input spike train. We quantitatively analyze the information about previous interspike intervals, contained in single responses of dynamic synapses, using methods from information theory applied to experimentally based deterministic and probabilistic phenomenological models of depressing and facilitating synapses. We show that for any given dynamic synapse, there exists an optimal frequency of presynaptic spike firing for which the information content is maximal; simple relations between this optimal frequency and the synaptic parameters are derived. Depressing neocortical synapses are optimized for coding temporal information at low firing rates of 0.5-5 Hz, typical to the spontaneous activity of cortical neurons, and carry significant information about the timing of up to four preceding presynaptic spikes. Facilitating synapses, however, are optimized to code information at higher presynaptic rates of 9-70 Hz and can represent the timing of over eight presynaptic spikes. PMID- 11784737 TI - Jittery trains induced by synaptic-like currents in cerebellar inhibitory interneurons. AB - Cerebellar inhibitory interneurons respond to parallel fiber input with a characteristic train of action potentials. Here we show that the characteristics of these trains reflect the intrinsic properties of the interneurons. In in vitro cerebellar slices, the response of these neurons to synaptic-like current resembles their in vivo response to parallel fiber input-a train of action potentials characterized by a gradual increase in interspike interval and spike amplitude. A large variability in spike timing, or jitter, was observed, the last action potential emerging from a slow depolarizing wave that lasted beyond the synaptic current and was prevented by either TTX or membrane hyperpolarization. While response duration was weakly dependent on current intensity, the variability of the overall duration was closely related to the variability of the timing of the last action potential. Blocking the Ca(2+) currents or partial blockade of the delayed rectifier (TEA 2 mM) decreased the excitability, leading to a decrease in the duration and variability of the response and increasing its dependence on stimulus intensity. Increased duration and variability was observed in the presence of Cs(+) ions (5 mM) that blocked an h-like current. We conclude that a persistent Na(+) current governs the duration of the response, whereas the synaptic current and the spiking mechanism shape its pattern. The large variability between trials is due to the stochastic nature of the persistent Na(+) current. Thus unless precise timing is achieved by a network of interconnected neurons, these results vote against temporal coding as a player in the cerebellar computational processing. PMID- 11784738 TI - Corticostriatal paired-pulse potentiation produced by voltage-dependent activation of NMDA receptors and L-type Ca(2+) channels. AB - AMPA and N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses expressed differential paired-pulse plasticity when examined in the same cell using intracellular or whole cell voltage-clamp recordings. Electrical stimulation of corticostriatal afferents in brain slices bathed in artificial cerebrospinal fluid containing bicuculline produces excitatory postsynaptic potentials and excitatory postsynaptic currents (EPSCs) mediated primarily by AMPA receptors. Cell-to-cell variation existed in AMPA receptor paired-pulse plasticity, but within-cell plasticity was stable over a range of stimulation intensities. Addition of 6-cyano-7-nitroquinoxalene-2,3-dione blocked most of the synaptic response leaving behind a small AP-5-sensitive component. Increasing the stimulation intensity produced large, long-lasting NMDA receptor-mediated responses. In contrast to AMPA receptor-mediated responses, NMDA receptor responses consistently showed an increase in paired-pulse potentiation with increasing stimulation intensity. This relationship was restricted to interstimulus intervals shorter than 100 ms. Paired-pulse potentiation of NMDA receptor responses was voltage-dependent and reduced by removal of extracellular Mg(2+). Block of postsynaptic L-type Ca(2+) channels with nifedipine produced a voltage-dependent reduction of NMDA receptor excitatory postsynaptic currents (EPSCs) and a voltage-dependent reduction of NMDA receptor paired-pulse potentiation. These data indicate depolarization during the first NMDA receptor response causes facilitation of the second by removing voltage-dependent block of NMDA receptors by Mg(2+) and by activating voltage-dependent Ca(2+) channels. PMID- 11784739 TI - Cholinergic influences on use-dependent plasticity. AB - Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system. PMID- 11784740 TI - On the interaction between voltage-gated conductances and Ca(2+) regulation mechanisms in retinal horizontal cells. AB - The horizontal cell is a second-order retinal neuron that is depolarized in the dark and responds to light with graded potential changes. In such a nonspiking neuron, not only the voltage-gated ionic conductances but also Ca(2+) regulation mechanisms, e.g., the Na(+)/Ca(2+) exchange and the Ca(2+) pump, are considered to play important roles in generating the voltage responses. To elucidate how these physiological mechanisms interact and contribute to generating the responses of the horizontal cell, physiological experiments and computer simulations were made. Fura-2 fluorescence measurements made on dissociated carp horizontal cells showed that intracellular Ca(2+) concentration ([Ca(2+)]i) was maintained <100 nM in the resting state and increased with an initial transient to settle at a steady level of approximately 600 nM during prolonged applications of L-glutamate (L-glu, 100 microM). A preapplication of caffeine (10 mM) partially suppressed the initial transient of [Ca(2+)]i induced by L-glu but did not affect the L-glu-induced steady [Ca(2+)]i. This suggests that a part of the initial transient can be explained by the Ca(2+)-induced Ca(2+) release from the caffeine-sensitive Ca(2+) store. The Ca(2+) regulation mechanisms and the ionic conductances found in the horizontal cell were described by model equations and incorporated into a hemi-spherical cable model to simulate the isolated horizontal cell. The physiological ranges of parameters of the model equations describing the voltage-gated conductances, the glutamate-gated conductance and the Na(+)/Ca(2+) exchange were estimated by referring to previous experiments. The parameters of the model equation describing the Ca(2+) pump were estimated to reproduce the steady levels of [Ca(2+)]i measured by Fura-2 fluorescence measurements. Using the cable model with these parameters, we have repeated simulations so that the voltage response and [Ca(2+)]i change induced by L-glu applications were reproduced. The simulation study supports the following conclusions. 1) The Ca(2+)-dependent inactivation of the voltage-gated Ca(2+) conductance has a time constant of approximately 2.86 s. 2) The falling phase of the [Ca(2+)]i transient induced by L-glu is partially due to the inactivation of the voltage-gated Ca(2+) conductance. 3) Intracellular Ca(2+) is extruded mainly by the Na(+)/Ca(2+) exchange when [Ca(2+)]i is more than approximately 2 microM and by the Ca(2+) pump when [Ca(2+)]i is less than approximately 1 microM. 4) In the resting state, the Na(+)/Ca(2+) exchange may operate in the reverse mode to induce Ca(2+) influx and the Ca(2+) pump extrudes intracellular Ca(2+) to counteract the influx. The model equations of physiological mechanisms developed in the present study can be used to elucidate the underlying mechanisms of the light-induced response of the horizontal cell in situ. PMID- 11784741 TI - Pre- and postsynaptic inhibition mediated by GABA(B) receptors in cerebellar inhibitory interneurons. AB - The inhibitory interneurons in the molecular layer of the cerebellar cortex form a complex network, interconnected by both chemical and electrotonic synapses. Previous work, using voltage optical imaging in an isolated cerebellum, has indicated that these interneurons also form presynaptic inhibitory interconnections. Here we examine the participation of GABA(B) receptors in the proposed presynaptic inhibition by recording from the molecular layer interneurons (MLI) in cerebellar slices. The GABA(B) agonist, baclofen, profoundly depressed synaptic transmission; a concentration of 10 microM decreased the frequency of spontaneous inhibitory synaptic potentials by 82 +/- 15% and of miniature synaptic potentials by 75 +/- 13%. In simultaneous recording from two synaptically interconnected MLIs, baclofen (10 microM) increased the failure rate of synaptic transmission by a factor of 3, confirming a presynaptic mechanism, most likely mediated by a decrease in calcium conductance. A postsynaptic effect of baclofen was also found; 10 microM decreased the spontaneous firing rate by 55 +/- 19% even in the presence of synaptic blockers. One hundred micromolar baclofen induced an averaged hyperpolarization of 6 +/- 2 mV or an averaged 7.8 +/- 3 pA net outward current that can account for the decrease in firing rate. The outward current reflects a reduction in a tonic Ca(2+) current, since it was abolished by blocking Ca(2+) currents and remained unchanged in the presence of Ba(2+). Application of the specific GABA(B) blocker, CGP 55845A (1 microM), not only reversed the effects of baclofen but also increased the spontaneous firing rate and synaptic activity when applied alone. Thus in slice preparations, GABA(B) receptors are tonically activated by endogenous GABA. The temporal role of GABA(B) receptors was tested using the paired-pulse paradigm. Recording from two synaptically interconnected MLIs showed a 3.5 times lower probability of release for the second stimulus. In the isolated cerebellar preparation, a robust depression of the second inhibitory response was observed. This depression was partially blocked by CGP 55845A (2 microM). We conclude that both the pre- and postsynaptic effects of baclofen are mediated by GABA(B) receptors that decrease Ca(2+) currents. These can serve a modulatory role as well as participating in shaping the temporal interactions between consecutive inputs. PMID- 11784742 TI - Quantitative analysis of the responses of V1 neurons to horizontal disparity in dynamic random-dot stereograms. AB - Horizontal disparity tuning for dynamic random-dot stereograms was investigated for a large population of neurons (n = 787) in V1 of the awake macaque. Disparity sensitivity was quantified using a measure of the discriminability of the maximum and minimum points on the disparity tuning curve. This measure and others revealed a continuum of selectivity rather than separate populations of disparity and nondisparity-sensitive neurons. Although disparity sensitivity was correlated with the degree of direction tuning, it was not correlated with other significant neuronal properties, including preferred orientation and ocular dominance. In accordance with the Gabor energy model, tuning curves for horizontal disparity were adequately described by Gabor functions when the neuron's orientation preference was near vertical. For neurons with orientation preferences near to horizontal, a Gaussian function was more frequently sufficient. The spatial frequency of the Gabor function that described the disparity tuning was weakly correlated with measurements of the spatial frequency and orientation preference of the neuron for drifting sinusoidal gratings. Energy models make several predictions about the relationship between the response rates to monocular and binocular dot patterns. Few of the predictions were fulfilled exactly, although the observations can be reconciled with the energy model by simple modifications. These same modifications also provide an account of the observed continuum in strength of disparity selectivity. A weak correlation between the disparity sensitivity of simultaneously recorded single- and multiunit data were revealed as well as a weak tendency to show similar disparity preferences. This is compatible with a degree of local clustering for disparity sensitivity in V1, although this is much weaker than that reported in area MT. PMID- 11784743 TI - Range and mechanism of encoding of horizontal disparity in macaque V1. AB - The responses of single cortical neurons were measured as a function of the binocular disparity of dynamic random dot stereograms for a large sample of neurons (n = 787) from V1 of the awake macaque. From this sample, we selected 180 neurons whose tuning curves were strongly tuned for disparity, well sampled and well described by one-dimensional Gabor functions. The fitted parameters of the Gabor functions were used to resolve three outstanding issues in binocular stereopsis. First, we considered whether tuning curves can be meaningfully divided into discrete tuning types. Careful examination of the distributions of the Gabor parameters that determine tuning shape revealed no evidence for clustering. We conclude that a continuum of tuning types is present. Second, we investigated the mechanism of disparity encoding for V1 neurons. The shape of the disparity tuning function can be used to distinguish between position-encoding (in which disparity is encoded by an interocular shift in receptive field position) and phase-encoding (in which disparity is encoded by a difference in the receptive field profile in the 2 eyes). Both position and phase encoding were found to be common. This was confirmed by an independent assessment of disparity encoding based on the measurement of disparity sensitivity for sinusoidal luminance gratings of different spatial frequencies. The contributions of phase and position to disparity encoding were compared by estimating a population average of the rate of change in firing rate per degree of disparity. When this was calculated separately for the phase and position contributions, they were found to be closely similar. Third, we investigated the range of disparity tuning in V1 as a function of eccentricity in the parafoveal range. We find few cells which are selective for disparities greater than +/-1 degrees even at the largest eccentricity of approximately 5 degrees. The preferred disparity was correlated with the spatial scale of the tuning curve, and for most units lay within a +/-pi radians phase limit. Such a size-disparity correlation is potentially useful for the solution of the correspondence problem. PMID- 11784744 TI - Role of Ca(2+) in the synchronization of transmitter release at calyceal synapses in the auditory system of rat. AB - The synchronization of transmitter release in the synapse of the medial nucleus of the trapezoid body (MNTB) is achieved during early postnatal development as a consequence of elimination of delayed asynchronous releases and appears to reflect changes in the dynamics of Ca(2+) entry and clearance. To examine the role of Ca(2+) in regulating synchronization of transmitter release in the mature synapse (after postnatal day 9, P9), we perturbed Ca(2+) dynamics systematically. Replacement of external Ca(2+) (2 mM) with Sr(2+) induced delayed asynchronous release following the major EPSC. We tried to reproduce asynchronous releases without using Sr(2+) and instead by manipulating the time course and the size of Ca(2+) transient in the presynaptic terminal, under the assumption that replacement of external Na(+) with Li(+) or application of eosin-Y would prolong the lifetime of Ca(2+) transient by reducing the rate of Ca(2+) extrusion from the terminal. With application of Li(+), Ca(2+) transient in the terminal was prolonged, the EPSC decay time course was prolonged, and the EPSC amplitude increased. However, these EPSCs were not followed by delayed asynchronous release. When Ca(2+) influx was reduced, either by partial Ca(2+) channel blockade with a low concentration of Cd(2+) or omega-agatoxin IVA, a marked asynchronous release resulted. This was further enhanced by the combined application of Li(+) or eosin-Y. These results suggest that cooperative increases of both Ca(2+) influx and Ca(2+) clearance capacities leading to a sharper Ca(2+) spike in the presynaptic terminal underlie synchronized transmitter release in the presynaptic terminal of the MNTB. PMID- 11784745 TI - Adaptive changes in locomotor activity following botulinum toxin injection in ankle extensor muscles of cats. AB - The present study investigated the adaptations made in motor behavior following a temporary reduction in ankle extensor activity in the walking cat. Temporary muscle weakness was induced by injecting botulinum toxin into the lateral gastrocnemius (LG), plantaris (PL), and soleus (SOL) muscles, or SOL alone. The medial gastrocnemius (MG) muscle was not injected. Adaptations in the level of muscle activity were recorded using chronically implanted electromyographic (EMG) electrodes. Serial recordings were made prior to botulinum toxin injections and for several days following the injections. Kinematic analysis of ankle joint movements was made from video records to assess the impact of the botulinum toxin injections on the function of the ankle joint during walking. Following injection of the LG, PL, and SOL muscles with botulinum toxin, the amplitude of the MG burst increased over a period of a few days to a week. This increase was similar to the previously reported changes produced in MG following transection of the nerves serving LG, PL, and SOL. Following the weakening of the ankle extensor muscles, there was a temporary deficit in ankle function during walking as evidenced by a marked increase in the amount of ankle flexion that occurred at stance onset. This functional deficit recovered relatively quickly and was not associated with a return of the EMG pattern to the preinjection pattern. After recovery from the initial injections, a second injection of botulinum toxin into SOL alone was performed. No functional deficits were observed in the ankle movements during walking following this second injection. However, weakening SOL produced increases in the burst amplitudes of the MG, LG, and PL muscles over a period of a few days. This suggests that normal movements at the ankle during walking can be generated with more than one pattern of ankle extensor activity and that there is flexibility in how the necessary torque is produced. A final procedure, transection of the nerves serving LG, PL, and SOL, failed to produce any functional deficits in ankle movements. The implication is that adaptations to the neural control of ankle extensor activity that were induced by the initial procedure persisted after the recovery of the injected muscles and were sufficient to compensate for the subsequent challenges. PMID- 11784746 TI - Background noise improves gap detection in tonically inhibited inferior colliculus neurons. AB - Single units in the inferior colliculus (IC) in the C57Bl/6 inbred mouse strain were tested for their temporal processing ability as measured by their minimum gap threshold (MGT), the shortest silent interval in an ongoing white-noise stimulus which a unit could encode. After ascertaining the MGT in quiet, units were re-tested in various levels of background noise. The focus of this report is on two types of tonically responding units found in the IC. Tonically inhibited (TI) units encoded gaps poorly in quiet and low levels of background noise as compared with tonically excited (TE) units. In quiet, the MGTs of TI units were about an order of magnitude longer than the MGTs typical of TE units. Paradoxically, gap encoding was improved in high levels of background noise for TI units. This result is unexpected from the traditional viewpoint that noise necessarily degrades signal processing and is inconsistent with psychophysical observations of diminished speech and gap detection processing in noisy environments. We believe the improved feature detection described here is produced by the adaptation of inhibitory input. Continuous background noise would diminish the inhibitory efficacy of the gap stimulus by increasing the latency to the onset of inhibition and decreasing its duration. This would allow more spontaneous activity to "bleed through" the silent gap, thus signaling its presence. Improved feature detection in background noise resulting from inhibitory adaptation would seem an efficient neural mechanism and one that might be generally useful in other signal detection tasks. PMID- 11784748 TI - Conjugate and vergence oscillations during saccades and gaze shifts: implications for integrated control of binocular movement. AB - Saccades made between targets at optical infinity require both eyes to rotate by the same angle. Nevertheless, these saccades are consistently accompanied by transient vergence eye movements. Here we have investigated whether the dynamics of these vergence movements depend on the trajectory of the coincident conjugate movement, and whether moving the head during eye-head gaze shifts modifies vergence dynamics. In agreement with previous reports, saccades with more symmetric (i.e., "bell-shaped") conjugate velocity profiles were accompanied by stereotyped biphasic vergence transients (i.e., a divergence phase immediately followed by a convergence phase). However, we found that saccades with more asymmetric, oscillatory-like dynamics (characterized by a typical conjugate reacceleration of the eyes following the initial peak velocity) were systematically accompanied by more complex vergence movements that also exhibited oscillatory-like dynamics. These findings could be extended to conditions where the head was free to move: comparable conjugate and vergence oscillations were observed during head-restrained saccades and combined eye-head gaze shifts. The duration of the vergence oscillation increased with gaze shift amplitude, such that as many as four vergence phases (divergence-convergence-divergence convergence) were recorded during 55 degrees gaze shifts (approximately 240 ms). To quantify these observations, we first determined whether conjugate and vergence peak velocities were systematically correlated. Conjugate peak velocity was linearly related to the peak velocity of the initial divergence phase for saccades and gaze shifts of all amplitudes, regardless of their dynamics. However, for more asymmetric saccades and gaze shifts, the subsequent convergence and divergence peak velocities were not correlated with either the initial peak conjugate velocity or the peak velocity of the conjugate reacceleration. Next, we determined that the duration of the different conjugate and vergence oscillation phases remained relatively constant across all saccades and gaze shifts, and that the conjugate and vergence profiles oscillated together at approximately 7.5-10 Hz. Using computer simulations, we show that a classic feed-forward model is unable to reproduce vergence oscillations based solely on peripheral mechanisms. Furthermore, we demonstrate that small modifications to the gain and delay of a simple feedback model for saccade generation can generate conjugate oscillations, and propose that such changes reflect the influence of lowered alertness on the tecto-reticular pathways. We conclude that peripheral mechanisms can only account for the initial divergence that accompanies all saccades, and that the conjugate and vergence oscillations observed during asymmetric movements arise centrally from an integrative binocular controller. PMID- 11784747 TI - Morphological and electrophysiological evidence for an ionotropic GABA receptor of novel pharmacology. AB - Evidence from toxicological studies suggested that an ionotropic GABA receptor of novel pharmacology (picrotoxin-insensitive, bicuculline-sensitive) exists in the chick embryo retina. In this report, we provide direct morphological and electrophysiological evidence for the existence of such an iGABA receptor. Chick embryo retinas (14-16 days old) incubated in the presence of kainic acid showed pronounced histopathology in all retinal layers. Maximal protection from this toxicity required a combination of bicuculline and picrotoxin. Individual application of the antagonists indicated that a picrotoxin-insensitive, bicuculline-sensitive GABA receptor is likely to be present on ganglion and amacrine, but not bipolar, cells. GABA currents in embryonic and mature chicken retinal neurons were measured by whole cell patch clamp. GABA was puffed at the dendritic processes in the IPL. Picrotoxin (500 microM, in the bath) eliminated all (>95%) the GABA current in the majority of ganglion and amacrine cells tested, but many cells possessed a substantial picrotoxin-insensitive component. This current was eliminated by bicuculline (200 microM). This current was not a transporter-associated current, since it was not altered by GABA transport blockers or sodium removal. The current-voltage relation was linear and reversed near E(Cl), as expected for a ligand-gated chloride current. Both pentobarbital and lorazepam enhanced the picrotoxin-insensitive current. We conclude that chicken retinal ganglion and amacrine cells express a GABA receptor that is GABA A-like, in that it can be blocked by bicuculline, and positively modulated by barbiturates and benzodiazepines, but is insensitive to the noncompetitive blocker picrotoxin. Understanding the molecular properties of this receptor will be important for understanding both physiological GABA neurotransmission and the pathology of GABA receptor overactivation. PMID- 11784750 TI - Tonic and phasic discharge patterns in toe flexor gamma-motoneurons during locomotion in the decerebrate cat. AB - To investigate the specificity of fusimotor (gamma) drive during locomotion, gamma-efferents were recorded from the flexor digitorum longus (FDL) and flexor hallucis longus (FHL) nerves in a decerebrate cat preparation. These nerves innervate hindlimb muscles that differ in some aspects of their mechanical action. For both FHL and FDL two stereotyped patterns of gamma activity were distinguished. Tonic units fired throughout the step cycle and had less modulation, but higher minimum rates, than phasic units, which were mainly recruited with ankle extensor [soleus (SOL)] electromyogram (EMG) activity. Differences in the relative timing of these patterns were apparent. In FHL the activity of phasic and most tonic neurons peaked after EMG onset. With FDL, tonic units generally reached maximum rate before, while phasic units peaked after, the beginning of EMG activity. During locomotion FHL and FDL alpha activity were rhythmically recruited with SOL. However, consistent with previous reports, FHL and FDL differed in their patterns of alpha activity. FHL was stereotyped while FDL was variable. Both FHL and FDL had activity related to ankle extensor EMG, but only FDL exhibited a peak around the end of this phase. No corresponding gamma activity was observed in FDL. In conclusion, 1) FHL and FDL received tonic and phasic fusimotor drive; 2) there was no alpha/gamma linkage for the late FDL alpha burst; 3) phasic gamma-efferents in both muscles received similar inputs, linked to plantar flexor alpha activity; and 4) tonic gamma-efferents differed, to the extent that they were modulated at all. The FHL units peaked with the plantar flexor alphas. The FDL neurons generally peaked before alpha activity even began. PMID- 11784749 TI - Response of MSTd neurons to simulated 3D orientation of rotating planes. AB - We studied whether the dorsal division of the medial superior temporal area (MSTd) in the macaque has activity related to structure-from-motion (SFM) processing. As the simplest form of three-dimensional (3D) structure, we chose a planar stimulus and examined the relation between the neural responses and the simulated 3D orientation of the plane defined by motion cues. We recorded from 114 MSTd neurons while monkeys were performing a visual fixation task. These neurons responded to a basic set of optic flow patterns such as translation, expansion/contraction, and rotation. Responses of these neurons to rotating plane stimuli were examined to see whether the MSTd neurons exhibited selectivity to the tilt and slant that characterize the 3D orientation of the plane. We found that most MSTd neurons tested (97 of 114) responded to the plane stimuli, and many neurons (65 of 97) exhibited selectivity to tilt and/or slant. Of 97 neurons, 18% (17/97) were selective only to tilt, 24% (23/97) only to slant, and 26% (25/97) to both. Control experiments rejected the possibility that the selectivity could be explained solely by the sensitivity to local stimulus components such as local translation, local speed, and local speed gradients. These results suggest that MSTd neurons are sensitive to stimulus features specific to the perceived 3D orientation of the rotating plane stimuli and suggest that area MSTd is involved in SFM processing. PMID- 11784751 TI - Human gaze stabilization during active head translations. AB - This study investigated how binocular gaze is controlled to compensate for self generated translational movements of the head where geometric requirements dictate that the ideal gaze signal needs to be modulated by the inverse of target distance. Binocular gaze (eye plus head) was measured for visual and remembered targets at various distances in six human subjects during active head translations at frequencies of 0.25, 0.5, 1.0, and 1.5 Hz. We found that, during head translations, gaze changes were achieved by a combination of eye and head rotations. Accordingly, stabilization performance was characterized by the gaze response parameters sensitivity and phase, where sensitivity is defined as the ratio of gaze velocity and translational eye velocity and where phase refers to the phase delay of gaze velocity relative to translational eye velocity. In the analysis, we used a binocular coordinate system yielding a version and a vergence component. We examined how frequency and target distance, estimated from the vergence angle, affected sensitivity and phase of the version component of the gaze signal and compared the results to the requirements for ideal performance. The relation between gaze sensitivity and the inverse of distance was characterized by a linear regression analysis. The ratio of the slope of the linear regression and the slope required for ideal stabilization provided a measure for the degree of "distance compensation." The results show that distance compensation was better for a visual target than for remembered targets in darkness, and behaved according to low-pass characteristics in both target conditions. It declined from 1.00 to 0.84 for visual targets and from 0.87 to 0.57 for remembered targets in the frequency range 0.25-1.5 Hz. The intercept obtained from the regression yielded the gaze response at zero vergence and specified a "default sensitivity" of gaze compensation. Default sensitivity increased with frequency from 0.02 at 0.25 Hz to 0.10 degrees/cm at 1.5 Hz for visual targets and from 0.04 to 0.16 degrees/cm in darkness. The phase delays of the gaze response increased on average from 2 to 7 degrees in the frequency range 0.25-1.5 Hz. In comparison with earlier passive studies, active translation compensation in the dark is superior at all frequencies where comparison was possible. We conclude that a nonvestibular signal with low-pass characteristics contributes to gaze during active head translations. PMID- 11784752 TI - Temporal modulation transfer functions in cat primary auditory cortex: separating stimulus effects from neural mechanisms. AB - We present here a comparison between the local field potentials (LFP) and multiunit (MU) responses, comprising 401 single units, in primary auditory cortex (AI) of 31 cats to periodic click trains, gamma-tone and time-reversed gamma-tone trains, AM noise, AM tones, and frequency-modulated (FM) tones. In a large number of cases, the response to all six stimuli was obtained for the same neurons. We investigate whether cortical neurons are likely to respond to all types of repetitive transients and modulated stimuli and whether a dependence on modulating waveform, or tone or noise carrier, exists. In 97% of the recordings, a temporal modulation transfer function (tMTF) for MU activity was obtained for gamma-tone trains, in 92% for periodic click trains, in 83% for time-reversed gamma-tone trains, in 82% for AM noise, in 71% for FM tones, and only in 53% for AM tones. In 31% of the cases, the units responded to all six stimuli in an envelope-following way. These particular units had significantly larger onset responses to each stimulus compared with all other units. The overall response distribution shows the preference of AI units for stimuli with short rise times such as clicks and gamma tones. It also shows a clear asymmetry in the ability to respond to AM noise and AM tones and points to a strong effect of the frequency content of the carrier on the subcortical processing of AM stimuli. Yet all temporal response properties were independent of characteristic frequency and frequency-tuning curve bandwidth. We show that the observed differences in the tMTFs for different stimuli are to a large extent produced by the different degree of phase locking of the neuronal firings to the envelope of the first stimulus in the train or first modulation period. A normalization procedure, based on these synchronization differences, unified the tMTFs for all stimuli except clicks and allowed the identification of a largely stimulus-invariant, low pass temporal filter function that most likely reflects the properties of synaptic depression and facilitation. For nonclick stimuli, the low-pass filter has a cutoff frequency of approximately 10 Hz and a slope of approximately 6 dB/octave. For nonclick stimuli, there was a systematic difference between the vector strength for LFPs and MU activity that can likely be attributed to postactivation suppression mechanisms. PMID- 11784753 TI - Morphological characteristics and central projections of two types of interneurons in the visual pathway of Hermissenda. AB - The synaptic interactions between photoreceptors in the eye and second-order neurons in the optic ganglion of the nudibranch mollusk Hermissenda are well characterized. However, the higher-order neural circuitry of the visual system, consisting of cerebropleural interneurons that receive synaptic input from photoreceptors and project to pedal motor neurons that mediate visually guided behaviors, is only partially understood. In this report we have examined the central projections of two identified classes of cerebropleural interneurons that receive excitatory or inhibitory synaptic input from identified photoreceptors. The classification of the interneurons was based on both morphological and electrophysiological criteria. Type I interneurons received monosynaptic excitatory or inhibitory synaptic input from identified photoreceptors and projected to postsynaptic targets within the cerebropleural ganglion. Type II interneurons, characterized here for the first time, received polysynaptic excitatory or inhibitory synaptic input from identified photoreceptors and projected to postsynaptic targets in either the ipsilateral pedal ganglion or the contralateral cerebropleural ganglion. Type I interneurons exhibited unique intraganglionic projections to different regions of the cerebropleural ganglion, depending on whether they received excitatory or inhibitory synaptic input from identified photoreceptors. Type I interneurons that received monosynaptic excitatory input from identified B photoreceptors terminated near the cerebropleural commissure and had multiple regions of varicosities located at branches that projected from the primary axon. Type I interneurons that received monosynaptic inhibitory input from identified B photoreceptors projected to the anterior cerebropleural ganglion and exhibited varicosities localized to the terminal region of the primary axonal process. Type II interneurons that received polysynaptic inhibitory input from identified photoreceptors projected to the contralateral cerebropleural ganglion. Most type II interneurons that projected to the pedal ganglia received polysynaptic excitatory input from identified photoreceptors. These results indicate that there is at least one additional interneuron in the higher-order visual circuit between type I interneurons and pedal motor neurons responsible for the generation of phototactic locomotion in Hermissenda. PMID- 11784754 TI - Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules? AB - In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection. PMID- 11784755 TI - A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina. AB - Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca(2+) currents (I(Ca)) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca(2+) channels that regulate the release of L-glutamate. In the retina, adenosine is released in the dark when L-glutamate release is maximal. We tested whether adenosine inhibits I(Ca) and intracellular Ca(2+) increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I(Ca) and the [Ca(2+)]i increase evoked by depolarization in a dose-dependent manner with approximately 25% inhibition at 50 microM. An A2-selective agonist, (N(6)-[2-(3,5 dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, (R)-N(6)-(1-methyl-2-phenylethyl)adenosine and N(6)-2-(4 aminophenyl)ethyladenosine, also inhibited I(Ca) and depolarization-induced [Ca(2+)]i increases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I(Ca) and the depolarization-evoked [Ca(2+)]i increase in rods. The results suggest that activation of A2 receptors stimulates PKA to inhibit L-type Ca(2+) channels in rods resulting in a decreased Ca(2+) influx that should suppress glutamate release. PMID- 11784756 TI - Auditory thalamocortical synaptic transmission in vitro. AB - To facilitate an understanding of auditory thalamocortical mechanisms, we have developed a mouse brain-slice preparation with a functional connection between the ventral division of the medial geniculate (MGv) and the primary auditory cortex (ACx). Here we present the basic characteristics of the slice in terms of physiology (intracellular and extracellular recordings, including current source density analysis), pharmacology (including glutamate receptor involvement), and anatomy (gross anatomy, Nissl, parvalbumin immunocytochemistry, and tract tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). Thalamocortical transmission in this preparation (the "primary" slice) involves both alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid/kainate and N methyl-D-aspartate-type glutamate receptors that appear to mediate monosynaptic inputs to layers 3-4 of ACx. MGv stimulation also initiates disynaptic inhibitory postsynaptic potentials and longer-duration intracortical, polysynaptic activity. Important differences between responses elicited by MGv versus conventional columnar ("on-beam") stimulation emphasize the necessity of thalamic activation to infer thalamocortical mechanisms. We also introduce a second slice preparation, the "shell" slice, obtained from the brain region immediately ventral to the primary slice, that may contain a nonprimary thalamocortical pathway to temporal cortex. In the shell slice, stimulation of the thalamus or the region immediately ventral to it appears to produce fast activation of synapses in cortical layer 1 followed by robust intracortical polysynaptic activity. The layer 1 responses may result from orthodromic activation of nonprimary thalamocortical pathways; however, a plausible alternative could involve antidromic activation of corticotectal neurons and their layer 1 collaterals. The primary and shell slices will provide useful tools to investigate mechanisms of information processing in the ACx. PMID- 11784757 TI - Principles of linear and angular vestibuloocular reflex organization in the frog. AB - We compared the spatial organization patterns of linear and angular vestibuloocular reflexes in frogs by recording the multiunit spike activity from cranial nerve branches innervating the lateral rectus, the inferior rectus, or the inferior obliquus eye muscles. Responses were evoked by linear horizontal and/or vertical accelerations on a sled or by angular accelerations about an earth-vertical axis on a turntable. Before each sinusoidal oscillation test in darkness, the static head position was systematically altered to determine those directions of horizontal linear acceleration and those planes of angular head oscillation that were associated with minimal response amplitudes. Inhibitory response components during angular accelerations were clearly present, whereas inhibitory response components during linear accelerations were absent. Likewise was no contribution from the vertical otolith organs (i.e., lagena and saccule) observed during vertical linear acceleration. Horizontal linear acceleration evoked responses that originated from eye muscle-specific sectors on the contralateral utricular macula. The sectors of the inferior obliquus and lateral rectus muscles on the utricle had an opening angle of 45 and 60 degrees, respectively and overlapped to a large extent in the laterorostral part of the utricle. Both sectors were coplanar with the horizontal semicircular canals. The sector of the inferior rectus muscle was narrow (opening 5 degrees), laterocaudally oriented, and slightly pitched up by 6 degrees. Angular acceleration evoked maximal responses in the inferior obliquus muscle nerve that originated from the ipsilateral horizontal and the contralateral anterior vertical canals in a ratio of 50:50. Lateral rectus excitation originated from the contralateral horizontal and anterior vertical semicircular canals in a ratio of 80:20. The excitatory responses of the inferior rectus muscle nerve originated exclusively from the contralateral posterior vertical canal. Measured data and known semicircular canal plane vectors were used to calculate the spatial orientation of maximum sensitivity vectors for the investigated eye muscle nerves in semicircular canal coordinates. Comparison of the directions of maximal sensitivity vectors of responses evoked by linear or angular accelerations in a given eye muscle nerve showed that the two vector directions were oriented about orthogonally with respect to each other. With this arrangement the linear and the angular vestibuloocular reflex can support each other dynamically whenever they are co-activated without a change in the spatial response characteristics. The mutual adaptation of angular and linear vestibuloocular reflexes as well as the differences in their organization described here for frogs may represent a basic feature common for vertebrates in general. PMID- 11784758 TI - Excitation and adaptation in the detection of hydrogen ions by taste receptor cells: a role for cAMP and Ca(2+). AB - The role of intracellular cAMP and Ca(2+) in the excitation and adaptation of taste responses by HCl was investigated by direct measurement of intracellular pH (pH(i)) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) nerve recordings. Stimulating the tongue with HCl concentrations between 1 and 30 mM caused a dose-dependent increase in CT responses that were insensitive to voltage clamp of the lingual receptive field and to amiloride. At a fixed HCl concentration (20 mM) topical lingual application of 8-chlorophenylthio(CPT)-cAMP increased the magnitude of HCl-induced CT response by twofold under zero current clamp. The magnitude of the CT response increased further at -60 mV and decreased at +60 mV lingual voltage clamp but remained amiloride insensitive. In untreated polarized TRCs, apical stimulation with HCl concentrations between 1 and 30 mM HCl induced sustained decreases in TRC pH(i). The magnitude of pH(i) decrease increased with increasing HCl concentration. Following treatment of the basolateral membrane with 8-CPT-cAMP the decrease in pH(i) due to apical 1 mM HCl application was significantly increased. Treatment with cAMP alone decreased resting TRC pH(i) and inhibited the recovery of pH(i) from a basolateral NH4Cl pulse by 46%. Topical lingual application of ionomycin, a Ca(2+) ionophore, did not affect the initial CT response to 20 mM HCl +10 mM CaCl2, but the response declined rapidly to 50% of its initial level within 2 min. In polarized TRCs, basolateral exposure to ionomycin increased TRC pH(i) and activated pH(i) recovery from NH4Cl pulse by 388%. Apical HCl stimulation induced a transient decrease in resting TRC pH(i) followed by spontaneous recovery. The data suggest that cAMP enhances the sour taste of strong acids by activating a Ca(2+)- and amiloride-insensitive H(+) conductance and inhibiting pH(i) recovery in TRCs. However, an increase in [Ca(2+)]i stimulates pH(i) recovery, which, in turn, increases sensory adaptation to acids. PMID- 11784759 TI - Independent representations of limb axis length and orientation in spinocerebellar response components. AB - Dorsal spinocerebellar tract (DSCT) neurons transmit sensory signals to the cerebellum that encode global hindlimb parameters, such as the hindlimb end-point position and its direction of movement. Here we use a population analysis approach to examine further the characteristics of DSCT neuronal responses during continuous movements of the hind foot. We used a robot to move the hind paw of anesthetized cats through the trajectories of a step or a figure-8 footpath in a parasagittal plane. Extracellular recordings from 82 cells converted to cycle histograms provided the basis for a principal-component analysis to determine the common features of the DSCT movement responses. Five principal components (PCs) accounted for about 80% of the total variance in the waveforms across units. The first two PCs accounted for about 60% of the variance and they were highly robust across samples. We examined the relationship between the responses and limb kinematic parameters by correlating the PC waveforms with waveforms of the joint angle and limb axis trajectories using multivariate linear regression models. Each PC waveform could be at least partly explained by a linear relationship to joint-angle trajectories, but except for the first PC, they required multiple angles. However, the limb axis parameters more closely related to both the first and second PC waveforms. In fact, linear regression models with limb axis length and orientation trajectories as predictors explained 94% of the variance in both PCs, and each was related to a particular linear combination of position and velocity. The first PC correlated with the limb axis orientation and orientation velocity trajectories, whereas second PC with the length and length velocity trajectories. These combinations were found to correspond to the dynamics of muscle spindle responses. The first two PCs were also most representative of the data set since about half the DSCT responses could be at least 85% accounted for by weighted linear combinations of these two PCs. Higher-order PCs were unrelated to limb axis trajectories and accounted instead for different dynamic components of the responses. The findings imply that an explicit and independent representation of the limb axis length and orientation may be present at the lowest levels of sensory processing in the spinal cord. PMID- 11784760 TI - Sound-level-dependent representation of frequency modulations in human auditory cortex: a low-noise fMRI study. AB - Recognition of sound patterns must be largely independent of level and of masking or jamming background sounds. Auditory patterns of relevance in numerous environmental sounds, species-specific vocalizations and speech are frequency modulations (FM). Level-dependent activation of the human auditory cortex (AC) in response to a large set of upward and downward FM tones was studied with low noise (48 dB) functional magnetic resonance imaging at 3 Tesla. Separate analysis in four territories of AC was performed in each individual brain using a combination of anatomical landmarks and spatial activation criteria for their distinction. Activation of territory T1b (including primary AC) showed the most robust level dependence over the large range of 48-102 dB in terms of activated volume and blood oxygen level dependent contrast (BOLD) signal intensity. The left nonprimary territory T2 also showed a good correlation of level with activated volume but, in contrast to T1b, not with BOLD signal intensity. These findings are compatible with level coding mechanisms observed in animal AC. A systematic increase of activation with level was not observed for T1a (anterior of Heschl's gyrus) and T3 (on the planum temporale). Thus these areas might not be specifically involved in processing of the overall intensity of FM. The rostral territory T1a of the left hemisphere exhibited highest activation when the FM sound level fell 12 dB below scanner noise. This supports the previously suggested special involvement of this territory in foreground-background decomposition tasks. Overall, AC of the left hemisphere showed a stronger level dependence of signal intensity and activated volume than the right hemisphere. But any side differences of signal intensity at given levels were lateralized to right AC. This might point to an involvement of the right hemisphere in more specific aspects of FM processing than level coding. PMID- 11784761 TI - Immediate changes in tuning of inferior colliculus neurons following acute lesions of cat spiral ganglion. AB - In previous studies, we demonstrated that acute lesions the spiral ganglion (SG), the cells of origin of the auditory nerve (AN), change the frequency organization of the inferior colliculus central nucleus (ICC) and primary auditory cortex (AI). In those studies, we used a map/re-map approach and recorded the tonotopic organization of neurons before and after restricted SG lesions. In the present study, response areas (RAs) of ICC multi-neuronal clusters were recorded to contralateral and ipsilateral tones after inserting and fixing-in-place tungsten microelectrodes. RAs were recorded from most electrodes before, immediately (within 33-78 min) after, and long (several hours) after restricted mechanical lesions of the ganglion. Each SG lesion produced a "notch" in the tone-evoked compound action potential (CAP) audiogram corresponding to a narrow range of lesion frequencies with elevated thresholds. Responses of contralateral IC neurons, which responded to these lesion frequencies, underwent an elevation in threshold to the lesion frequencies with either no change in sensitivity to other frequencies or with dramatic decreases in threshold to lesion-edge frequencies. These changes in sensitivity produced shifts in characteristic frequency (CF) that could be more than an octave. Thresholds at these new CFs matched the prelesion thresholds of neurons tuned to the lesion-edge frequencies. Responses evoked by ipsilateral tones delivered to the intact ear often underwent complementary changes, i.e., decreased thresholds to lesion frequency tones with little or no change in sensitivity to other frequencies. These results indicate that responses of IC neurons are produced by convergence of auditory information across a wide range of AN fibers and that the acute "plastic" changes reported in our previous studies occur within 1 h of an SG lesion. PMID- 11784762 TI - Spinal projections of the cat parvicellular red nucleus. AB - Traditionally, the red nucleus of the cat is divided into two parts: a large celled, magnocellular, division (RNm) and a small-celled, parvicellular, division (RNp). The RNm projects to the spinal cord and receives input from the cerebellar interpositus nucleus. The RNp projects to the inferior olive and receives input from the cerebellar dentate nucleus. In this report, we reexamine the connections of the red nucleus using the bidirectional tracer wheat germ agglutinin horseradish peroxidase (WGA-HRP). Our findings demonstrate that the cat RNp has a large caudal and lateral region that projects to contralateral spinal cord and not to the inferior olive. The spinally projecting region of RNp receives input from the dentate nucleus and a lateral segment of anterior interpositus. Cervical projections from the red nucleus show a topography with the rostral portion of RNp favoring upper segments and the caudal portion of RNm favoring lower segments. The results show that dentate output can influence spinal activity without passing through the cerebral cortex. For the control of movements such as reaching and grasping, we suggest that RNp and dentate focus on the control of proximal limb musculature, whereas RNm and the anterior interpositus focus on the control of distal limb musculature. We also suggest that other species are likely to have a small-celled area of red nucleus projecting to the spinal cord. PMID- 11784763 TI - Functional specialization within the cat red nucleus. AB - Magnocellular (RNm) and parvicellular (RNp) divisions of the cat red nucleus (RN) project to the cervical spinal cord. RNp projects more heavily to upper cervical levels and RNm projects more heavily to lower levels. The cells in RN are active during reaching and grasping, and the differences in termination suggest that the divisions influence different musculature during this behavior. However, the spinal termination may not reflect function because most rubrospinal terminations are to interneuronal regions, which can influence motor neurons at other spinal levels. To test for functional differences between RNm and RNp, we selectively stimulated RNm and RNp as well as the efferent fibers from each region. Electromyographic activity was recorded from seven muscles of the cat forelimb during reaching. The activity from each muscle was averaged over several thousand stimuli to detect influences of stimulation on muscle activity. Stimulation within the RN produced a characteristic pattern of poststimulus effects. The digit dorsiflexor, extensor digitorum communis (edc), was most likely to show facilitation, and several other muscles showed suppression. The pattern of activation did not differ between RNm and RNp. In contrast, stimulation of RNp fibers favored facilitation of shoulder muscles (spinodeltoideus and supraspinatus), and stimulation of RNm fibers favored facilitation of digit and wrist muscles (edc, palmaris longus, and extensor carpi ulnaris). Fiber stimulation produced few instances of poststimulus suppression. The results from fiber stimulation indicate that the physiological actions of RNm and RNp match their levels of spinal termination. The complex pattern of facilitation and suppression seen with RN stimulation may reflect synaptic actions within the nucleus. PMID- 11784764 TI - Auditory cortical images of cochlear-implant stimuli: dependence on electrode configuration. AB - This study examines patterns of auditory cortical activity elicited by single pulse cochlear implant stimuli that vary in electrode configuration, cochlear place of stimulation, and stimulus level. Recordings were made from the primary auditory cortex (area A1) of ketamine-anesthetized guinea pigs. The spatiotemporal pattern of neural spike activity was measured simultaneously across 16 cortical locations spanning approximately 2-3 octaves of the tonotopic axis. Such a pattern, averaged over 40 presentations of any particular stimulus, was defined as the "cortical image" of that stimulus. Acutely deafened guinea pigs were implanted with a 6-electrode animal version of the 22-electrode Nucleus banded electrode array (Cochlear). Cochlear electrode configurations consisted of monopolar (MP), bipolar (BP + N) with N inactive electrodes between the active and return electrodes (0 < or = N < or = 4), tripolar (TP) with one active electrode and two flanking return electrodes, and common ground (CG) with one active electrode and as many as five return electrodes. Cortical images typically showed a focus of maximum spike probability and minimum latency. Spike probabilities tended to decrease, and latencies tended to increase, with increasing cortical distance from that focus. Cortical images of TP stimuli were the most spatially compact, followed by BP + N images, and then MP images, which were the broadest. Images of CG stimuli were rather variable across animals and stimulus channels. The locations of cortical images shifted systematically from caudal to rostral as the cochlear place of stimulation changed from basal to apical. At the most sensitive cortical site for each condition, the dynamic ranges over which spike rates increased with increased current level were restricted to about 1-2 dB, regardless of configuration. Dynamic ranges tended to increase with increasing cortical distance from the most sensitive site. Electrode configurations that produced compact cortical images (e.g., TP and BP + 0) showed the greatest range of thresholds within each cortical image and the largest dynamic range at cortical sites removed from the most sensitive site. PMID- 11784765 TI - Auditory cortical images of cochlear-implant stimuli: coding of stimulus channel and current level. AB - This study quantified the accuracy with which populations of neurons in the auditory cortex can represent aspects of electrical cochlear stimuli presented through a cochlear implant. We tested the accuracy of coding of the place of stimulation (i.e., identification of the active stimulation channel) and of the stimulus current level. Physiological data came from the companion study, which recorded spike activity of neurons simultaneously from 16 sites along the tonotopic axis of the guinea pig's auditory cortex. In that study, cochlear electrical stimuli were presented to acutely deafened animals through a 6 electrode animal version of the 22-electrode Nucleus banded electrode array (Cochlear). Cochlear electrode configurations consisted of monopolar (MP), bipolar (BP + N) with N inactive electrodes between the active and return electrodes (0 < or = N < or = 3), tripolar (TP) with one active electrode and two flanking return electrodes, and common ground (CG) with one active electrode and as many as five return electrodes. In the present analysis, an artificial neural network was trained to recognize spatiotemporal patterns of cortical activity in response to single presentations of particular stimuli and, thereby, to identify those stimuli. The accuracy of pair-wise discrimination of stimulation channels or of current levels was represented by the discrimination index, d', where d' = 1 was taken as threshold. In many cases, the threshold for discrimination of place of cochlear stimulation was < 0.75 mm, and the threshold for discrimination of current levels was < 1 dB. Cochlear electrode configurations varied in the accuracy with which they signaled to the auditory cortex the place of cochlear stimulation. The BP + N and TP configurations provided considerably greater sensitivity to place of stimulation than did the MP configuration. The TP configuration maintained accurate signaling of place of stimulation up to the highest current levels, whereas sensitivity was degraded at high current levels in BP + N configurations. Electrode configurations also varied in the dynamic range over which they signaled stimulus current level. Dynamic ranges were widest for the BP + 0 configuration and narrowest for the TP configuration. That is, the configuration that showed the most accurate signaling of cochlear place of stimulation (TP) showed the most restricted dynamic range for signaling of current level. These results suggest that the choice of the optimal electrode configuration for use by human cochlear-prosthesis users would depend on the particular demands of the speech-processing strategy that is to be employed. PMID- 11784766 TI - Reward-dependent spatial selectivity of anticipatory activity in monkey caudate neurons. AB - Many neurons show anticipatory activity in learned tasks. This phenomenon appears to reflect the brain's ability to predict future events. However, what actually is predicted is unknown. Using a memory-guided saccade task, in which only one out of four directions was rewarded in each block of trials, we found that a group of neurons in the monkey caudate nucleus (CD) showed activity before presentation of an instruction cue stimulus. Among 329 CD neurons that were related to memory-guided saccade tasks, 156 showed the precue activity and 91 of them were examined fully. Remarkably, the magnitude of the precue activity varied across the four blocks of the one-direction-rewarded (1DR) condition, depending on which direction was rewarded. A majority of neurons with precue activity (83/91, 91%) showed significant directional preference. The best and worst directions were usually in the contralateral and ipsilateral directions, respectively. Within a block, the precue activity increased rapidly for the best direction in 1DR and decreased gradually for the worst direction in 1DR and all directions-rewarded (ADR) condition. The precue activity was weak in ADR. The precue activity did not reflect the likelihood of a particular cue stimulus, because the probability of the cue appearing in each direction was the same regardless of the rewarded direction. These results suggest that each CD neuron indicates a particular position-reward association prospectively, usually with contralateral preference. Assuming that the CD neurons have access to saccadic motor outputs, the precue activity would create a motivational bias toward the contralateral space, even before an instruction is given by the cue stimulus. PMID- 11784767 TI - Spectrotemporal receptive fields in the lemniscal auditory thalamus and cortex. AB - Receptive fields have been characterized independently in the lemniscal auditory thalamus and cortex, usually with spectrotemporally simple sounds tailored to a specific task. No studies have employed naturalistic stimuli to investigate the thalamocortical transformation in temporal, spectral, and aural domains simultaneously and under identical conditions. We recorded simultaneously in the ventral division of the medial geniculate body (MGBv) and in primary auditory cortex (AI) of the ketamine-anesthetized cat. Spectrotemporal receptive fields (STRFs) of single units (n = 387) were derived by reverse-correlation with a broadband and dynamically varying stimulus, the dynamic ripple. Spectral integration, as measured by excitatory bandwidth and spectral modulation preference, was similar across both stations (mean Q(1/e) thalamus = 5.8, cortex = 5.4; upper cutoff of spectral modulation transfer function, thalamus = 1.30 cycles/octave, cortex = 1.37 cycles/octave). Temporal modulation rates slowed by a factor of two from thalamus to cortex (mean preferred rate, thalamus = 32.4 Hz, cortex = 16.6 Hz; upper cutoff of temporal modulation transfer function, thalamus = 62.9 Hz, cortex = 37.4 Hz). We found no correlation between spectral and temporal integration properties, suggesting that the excitatory-inhibitory interactions underlying preference in each domain are largely independent. A small number of neurons in each station had highly asymmetric STRFs, evidence of frequency sweep selectivity, but the population showed no directional bias. Binaural preferences differed in their relative proportions, most notably an increased prevalence of excitatory contralateral-only cells in cortex (40%) versus thalamus (23%), indicating a reorganization of this parameter. By comparing simultaneously along multiple stimulus dimensions in both stations, these observations establish the global characteristics of the thalamocortical receptive field transformation. PMID- 11784768 TI - Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. AB - Results presented in this study indicate that a large subpopulation (approximately 65%) of hippocampal astrocytes in situ exhibit calcium oscillations in the absence of neuronal activity. Further, the spontaneous oscillations observed within individual hippocampal astrocytes generally developed asynchronously throughout the astrocyte's fine processes and occasionally spread through a portion of that astrocyte as a calcium wave but do not appear to spread among astrocytes as an intercellular calcium wave. Bath application of cyclopiazonic acid and injection of individual astrocytes with heparin blocked astrocytic calcium oscillations. Application of tetrodotoxin or incubation of slices with bafilomycin A1 had no effect on astrocytic calcium oscillations but did block evoked and spontaneous postsynaptic currents measured in CA1 pyramidal neurons. Application of a cocktail of antagonists for metabotropic glutamate receptors and purinergic receptors had no effect on the astrocytic calcium oscillations but blocked the ability of purinergic and metabotropic glutamatergic agonists to increase astrocytic calcium levels. These results indicate that the spontaneous calcium oscillations observed in hippocampal astrocytes in situ are mediated by IP3 receptor activation, are not dependent on neuronal activity, and do not depend on activation of metabotropic glutamate receptors or purinergic receptors. To our knowledge, this is the first demonstration that astrocytes in situ exhibit intrinsic signaling. This finding supports the hypothesis that astrocytes, independent of neuronal input, may act as pacemakers to modulate neuronal activity in situ. PMID- 11784769 TI - Electrical coupling can prevent expression of adult-like properties in an embryonic neural circuit. AB - Electrical coupling is widespread in developing nervous systems and plays a major role in circuit formation and patterning of activity. In most reported cases, such coupling between rhythmogenic neurons tends to synchronize and enhance their oscillatory behavior, thereby producing monophasic rhythmic output. However, in many adult networks, such as those responsible for rhythmic motor behavior, oscillatory neurons are linked by synaptic inhibition to produce rhythmic output with multiple phases. The question then arises whether such networks are still able to generate multiphasic output in the early stage of development when electrical coupling is abundant. A suitable model for addressing this issue is the lobster stomatogastric nervous system (STNS). In the adult animal, the STNS consists of three discrete neural networks that are comprised of oscillatory neurons interconnected by reciprocal inhibition. These networks generate three distinct rhythmic motor patterns with large amplitude neuronal oscillations. By contrast, in the embryo the same neuronal population expresses a single multiphasic rhythm with small-amplitude oscillations. Recent findings have revealed that adult-like network properties are already present early in the embryonic system but are masked by an as yet unknown mechanism. Here we use computer simulation to test whether extensive electrical coupling may be involved in masking adult-like properties in the embryonic STNS. Our basic model consists of three different adult-like STNS networks that are built of relaxation oscillators interconnected by reciprocal synaptic inhibition. Individual model cells generate slow membrane potential oscillations without action potentials. The introduction of widespread electrical coupling between members of these networks dampens oscillation amplitudes and, at moderate coupling strengths, may coordinate neuronal activity into a single rhythm with different phases, which is strongly reminiscent of embryonic STNS output. With a further increase in coupling strength, the system reaches one of two final states depending on the relative contribution of inhibition and inherent oscillatory properties within the networks: either fully synchronized and dampened oscillations, or a complete collapse of activity. Our simulations indicate that, beginning from either of these two states, the emergence of distinct adult networks during maturation may arise from a developmental decrease in electrical coupling that unmasks preexisting adult-like network properties. PMID- 11784770 TI - alpha7 nicotinic acetylcholine receptors on GABAergic interneurons evoke dendritic and somatic inhibition of hippocampal neurons. AB - GABAergic interneurons in the hippocampus express high levels of alpha7 nicotinic acetylcholine receptors, but because of the diverse roles played by hippocampal interneurons, the impact of activation of these receptors on hippocampal output neurons (i.e., CA1 pyramidal cells) is unclear. Activation of hippocampal interneurons could directly inhibit pyramidal neuron activity but could also produce inhibition of other GABAergic cells leading to disinhibition of pyramidal cells. To characterize the inhibitory circuits activated by these receptors, exogenous acetylcholine was applied directly to CA1 interneurons in hippocampal slices, and the resulting postsynaptic responses were recorded from pyramidal neurons or interneurons. Inhibitory currents mediated by GABA(A) receptors were observed in 27/131 interneuron/pyramidal cell pairs, but no instances of disinhibition of spontaneous inhibitory events or GABA(B) receptor-mediated responses were observed. Two populations of bicuculline-sensitive GABA(A) receptor-mediated currents could be distinguished based on their kinetics and amplitude. Anatomical reconstructions of the interneurons in a subset of connected pairs support the hypothesis that these two populations correspond to inhibitory synapses located either on the somata or dendrites of pyramidal cells. In 11 interneuron/interneuron cell pairs, one presynaptic neuron was observed that produced strong inhibitory currents in several nearby interneurons, suggesting that disinhibition of pyramidal neurons may also occur. All three types of inhibitory responses (somatic-pyramidal, dendritic-pyramidal, and interneuronal) were blocked by the alpha7 receptor-selective antagonist methyllycaconitine. These data suggest activation of these functionally distinct circuits by alpha7 receptors results in significant inhibition of both hippocampal pyramidal neurons as well as interneurons. PMID- 11784771 TI - Y5 receptors mediate neuropeptide Y actions at excitatory synapses in area CA3 of the mouse hippocampus. AB - Neuropeptide Y (NPY) is a potent modulator of excitatory synaptic transmission and limbic seizures. NPY is abundantly expressed in the dentate gyrus and is thought to modulate hippocampal excitability via activation of presynaptic Y2 receptors (Y2R). Here we demonstrate that NPY, and commonly used Y2R-preferring (NPY(13-36)) and Y5 receptor (Y5R)-preferring ([D-Trp(32)]NPY and hPP) peptide agonists, evoke similar levels of inhibition at excitatory CA3 synapses in hippocampal slices from wild-type control mice (WT). In contrast, NPYergic inhibition of excitatory CA3 synaptic transmission is absent in mice lacking the Y5R subtype (Y5R KO). In both analyses of evoked population spike activity and spontaneous excitatory postsynaptic synaptic currents (EPSCs), NPY agonists induced powerful inhibitory effects in all hippocampal slices from WT mice, whereas these peptides had no effect in slices from Y5R KO mice. In slices from WT mice, NPY (and NPY receptor-preferring agonists) reduced the frequency of spontaneous EPSCs but had no effect on sEPSC amplitude, rise time, or decay time. Furthermore, NPYergic modulation of spontaneous EPSCs in WT mice was mimicked by bath application of a novel Y5R-selective peptide agonist ([cpp]hPP) but not the selective Y2R agonist ([ahx(5-24)]NPY). In situ hybridization was used to confirm the presence of NPY, Y2, and Y5 mRNA in the hippocampus of WT mice and the absence of Y5R in knockout mice. These results suggest that the Y5 receptor subtype, previously believed to mediate food intake, plays a critical role in modulation of hippocampal excitatory transmission at the hilar-to-CA3 synapse in the mouse. PMID- 11784772 TI - Prefrontal task-related activity representing visual cue location or saccade direction in spatial working memory tasks. AB - To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90 degrees clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period. PMID- 11784774 TI - Evidence for a widespread brain stem escape network in larval zebrafish. AB - Zebrafish escape behaviors, which typically consist of a C bend, a counter-turn, and a bout of rapid swimming, are initiated by firing of the Mauthner cell and two segmental homologs. However, after laser-ablation of the Mauthner cell and its homologs, escape-like behaviors still occur, albeit at a much longer latency. This might suggest that additional neurons contribute to this behavior. We therefore recorded the activity of other descending neurons in the brain stem using confocal imaging of cells retrogradely labeled with fluorescent calcium indicators. A large majority of identified descending neurons present in the larval zebrafish, including both ipsilaterally and contralaterally projecting reticulospinal neurons, as well as neurons from the nucleus of the medial longitudinal fasciculus, showed short-latency calcium responses after gentle taps to the head of the larva-a stimulus that reliably evokes an escape behavior. Previous studies had associated such in vivo calcium responses with the firing of action potentials, and because all responding cells have axons projecting into to spinal cord, this suggests that these cells are relaying escape-related information to spinal cord. Other identified neurons failed to show consistent calcium responses to escape-eliciting stimuli. In conjunction with previous lesion studies, these results indicate that the neural control systems for turning and swimming behaviors are widely distributed in the larval zebrafish brain stem. The degree of robustness or redundancy of this system has implications for the descending control of vertebrate locomotion. PMID- 11784773 TI - Adaptive changes in early and late blind: a fMRI study of Braille reading. AB - Braille reading depends on remarkable adaptations that connect the somatosensory system to language. We hypothesized that the pattern of cortical activations in blind individuals reading Braille would reflect these adaptations. Activations in visual (occipital-temporal), frontal-language, and somatosensory cortex in blind individuals reading Braille were examined for evidence of differences relative to previously reported studies of sighted subjects reading print or receiving tactile stimulation. Nine congenitally blind and seven late-onset blind subjects were studied with fMRI as they covertly performed verb generation in response to reading Braille embossed nouns. The control task was reading the nonlexical Braille string "######". This study emphasized image analysis in individual subjects rather than pooled data. Group differences were examined by comparing magnitudes and spatial extent of activated regions first determined to be significant using the general linear model. The major adaptive change was robust activation of visual cortex despite the complete absence of vision in all subjects. This included foci in peri-calcarine, lingual, cuneus and fusiform cortex, and in the lateral and superior occipital gyri encompassing primary (V1), secondary (V2), and higher tier (VP, V4v, LO and possibly V3A) visual areas previously identified in sighted subjects. Subjects who never had vision differed from late blind subjects in showing even greater activity in occipital-temporal cortex, provisionally corresponding to V5/MT and V8. In addition, the early blind had stronger activation of occipital cortex located contralateral to the hand used for reading Braille. Responses in frontal and parietal cortex were nearly identical in both subject groups. There was no evidence of modifications in frontal cortex language areas (inferior frontal gyrus and dorsolateral prefrontal cortex). Surprisingly, there was also no evidence of an adaptive expansion of the somatosensory or primary motor cortex dedicated to the Braille reading finger(s). Lack of evidence for an expected enlargement of the somatosensory representation may have resulted from balanced tactile stimulation and gross motor demands during Braille reading of nouns and the control fields. Extensive engagement of visual cortex without vision is discussed in reference to the special demands of Braille reading. It is argued that these responses may represent critical language processing mechanisms normally present in visual cortex. PMID- 11784775 TI - A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities. AB - Stimulus salience depends both on behavioral context and on other factors such as novelty and frequency of occurrence. The temporo-parietal junction (TPJ) responds preferentially to behaviorally relevant stimuli and is thought to play a general role in detecting salient stimuli. If so, it should respond preferentially to novel or infrequent events, even in a neutral behavioral context. To test this hypothesis, we used event-related functional magnetic resonance imaging (fMRI) to identify brain regions sensitive to the novelty of visual, auditory, and tactile stimuli during passive observation. Cortical regions with a greater response to novel than familiar stimuli across all modalities were identified at two sites in the TPJ region: the supramarginal gyrus (SMG) and superior temporal gyrus. The right inferior frontal gyrus (IFG), right anterior insula, left anterior cingulate cortex (ACC), and left inferior temporal gyrus also showed sensitivity to novelty. The novelty-sensitive TPJ activation in SMG overlaps a region previously identified as sensitive behavioral context. This region may play a general role in identifying salient stimuli, whether the salience is due to the current behavioral context or not. The IFG activation overlaps regions previously identified as responsive to nonnovel sensory events regardless of behavioral context. The IFG may therefore play a general role in stimulus evaluation rather than a specific role in identifying novel stimuli. The ACC activation lies in a region active during complex response-selection tasks, suggesting a general role in detecting and/or planning responses to salient events. A frontal-parietal cingulate network may serve to identify and evaluate salient sensory stimuli in general. PMID- 11784777 TI - Synchronized spikes of thalamocortical axonal terminals and cortical neurons are detectable outside the pig brain with MEG. AB - We show that it is feasible to monitor the synchronized population spikes of the thalamocortical axonal terminals and cortical neurons outside the brain using high-resolution magnetoencephalography (MEG). Electrical stimulation of the snout elicited somatic-evoked magnetic fields (SEFs) above the primary somatosensory cortex (SI) of the piglet. The SEFs contained high-frequency oscillations (HFOs) around 600 Hz similar in many respects to the noninvasively measured HFOs from humans with MEG and electroencephalography (EEG). These HFOs were highly correlated with those in simultaneously measured intracortical somatic-evoked potentials (SEPs) in the snout projection area in SI. Both HFOs in SEFs and SEPs consisted of an initial component insensitive to cortically injected kynurenic acid (Kyna, 20 mM), a nonspecific antagonist of glutamatergic receptors, and a subsequent Kyna-sensitive component. The former was localized in cortical layer IV, indicating that it was due to spikes produced by the specific thalamocortical axonal terminals, whereas the latter was initially localized in layer IV and subsequently in the superficial and deeper layers. These results suggest that it may be possible to study properties of the thalamocortical and cortical spike activities in humans with MEG. PMID- 11784776 TI - Differential roles for mGluR1 and mGluR5 in the persistent prolongation of epileptiform bursts. AB - Transient activation of group I metabotropic glutamate receptors (mGluRs) with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces persistent prolongation of epileptiform bursts in guinea pig hippocampal slices, the maintenance of which can be reversibly suppressed with group I mGluR antagonists. To determine the relative roles of mGluR1 and mGluR5 in these group I mGluR dependent induction and maintenance processes, subtype-selective antagonists were utilized. In the presence of picrotoxin, DHPG (50 microM, 20-45 min) converted interictal bursts into 1- to 3-s discharges that persisted for hours following washout of the mGluR agonist. 2-methyl-6-(phenylethynyl)-pyridine (MPEP, an mGluR5 antagonist; 25 microM) and (+)-2-methyl-4-carboxyphenylglycine (LY367385, an mGluR1 antagonist; 20-25 microM) each significantly suppressed the ongoing expression of the mGluR-induced prolonged bursts. However, LY367385 was more effective, reducing the burst prolongation by nearly 90%; MPEP only produced a 64% reduction in burst prolongation. Nevertheless, MPEP was more effective at preventing the induction of the burst prolongation; all 10 slices tested failed to express prolonged bursts both during and after co-application of DHPG with MPEP. Co-application of DHPG with LY367385, in contrast, resulted in significant burst prolongation (in 68% of slices tested) that was revealed on washout of the two agents. These results suggest that while both receptor subtypes participate in both the induction and maintenance of mGluR-mediated burst prolongation, mGluR1 activation plays a greater role in sustaining the expression of prolonged bursts, whereas mGluR5 activation may be a more critical contributor to the induction process underlying this type of epileptogenesis. PMID- 11784778 TI - Fornix transection impairs conditional visuomotor learning in tasks involving nonspatially differentiated responses. AB - Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response. PMID- 11784779 TI - Limbic network interactions leading to hyperexcitability in a model of temporal lobe epilepsy. AB - In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4 aminopyridine (4AP, 50 microM) in hippocampus-EC slices from mice injected with pilocarpine 13-22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (< or = 6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path. PMID- 11784780 TI - Glycine receptors involved in synaptic transmission are selectively regulated by the cytoskeleton in mouse spinal neurons. AB - Using whole cell patch-clamp recordings, we examined the effect of colchicine, a microtubule disrupter, on the properties of glycine receptors (GlyRs) in cultured spinal cord neurons. Confocal microscopy revealed that colchicine treatment effectively altered microtubule bundles and neuronal morphology. Application of colchicine via the culture media or the patch-pipette, however, did not affect the whole cell current rundown (73 +/- 6% of control after 1 h), the sensitivity of the GlyR to glycine (EC(50) = 29 +/- 1 microM), or strychnine inhibition (47 +/- 5% of control after 100 nM strychnine). On the other hand, colchicine dialyzed for 25 min via the patch pipette selectively reduced the quantal amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents (mIPSCs) to 68 +/- 5% of control. This effect was specific for GlyRs since synaptic events mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and GABA(A) receptors were unchanged. In conclusion, this study indicates that microtubules can regulate the function of GlyRs involved in inhibitory synaptic transmission. PMID- 11784781 TI - Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. AB - The amyloid precursor protein (APP) of Alzheimer's disease (AD) has a copper binding domain (CuBD) located in the N-terminal cysteine-rich region that can strongly bind copper(II) and reduce it to Cu(I) in vitro. The CuBD sequence is similar among the APP family paralogs [amyloid precursor-like proteins (APLP1 and APLP2)] and its orthologs (including Drosophila melanogaster, Xenopus laevis, and Caenorhabditis elegans), suggesting an overall conservation in its function or activity. The APP CuBD is involved in modulating Cu homeostasis and amyloid beta peptide production. In this paper, we demonstrate for the first time that Cu metallated full-length APP ectodomain induces neuronal cell death in vitro. APP Cu neurotoxicity can be induced directly or potentiated through Cu(I)-mediated oxidation of low-density lipoprotein, a finding that may have important implications for the role of lipoproteins and membrane cholesterol composition in AD. Cu toxicity induced by human APP, Xenopus APP, and APLP2 CuBDs is dependent on conservation of histidine residues at positions corresponding to 147 and 151 of human APP. Intriguingly, APP orthologs with different amino acid residues at these positions had dramatically altered Cu phenotypes. The corresponding C. elegans APL-1 CuBD, which has tyrosine and lysine residues at positions 147 and 151, respectively, strongly protected against Cu-mediated lipid peroxidation and neurotoxicity in vitro. Replacement of histidines 147 and 151 with tyrosine and lysine residues conferred this neuroprotective Cu phenotype to human APP, APLP2, and Xenopus APP CuBD peptides. Moreover, we show that the toxic and protective CuBD phenotypes are associated with differences in Cu binding and reduction. These studies identify a significant evolutionary change in the function of the CuBD in modulating Cu metabolism. Our findings also suggest that targeting of inhibitors to histidine residues at positions 147 and 151 of APP could significantly alter the oxidative potential of APP. PMID- 11784782 TI - Modulatory mechanism of the endogenous peptide catestatin on neuronal nicotinic acetylcholine receptors and exocytosis. AB - The catestatin fragment of chromogranin A is the first known endogenous compound able to inhibit catecholamine release elicited by the activation of neuronal nicotinic acetylcholine receptors (nAChRs) of different animal species and catecholaminergic cell types. However, how catestatin regulates the receptor activity, which subunit combination of the heteropentameric forms of receptor is better blocked by the peptide, or how it affects the different stages of the exocytotic process have not yet been evaluated. To address these questions, we have assayed the effects of catestatin: (first) on the inward currents elicited by ACh (I(ACh)) in voltage-clamped oocytes expressing different combinations of nAChR subunits; and (second) on the cytosolic Ca2+ concentration, [Ca2+]c, and quantal release of catecholamines simultaneously monitored in single adrenal chromaffin cells stimulated with ACh. Catestatin potently blocks all the subtypes of nAChRs studied. Furthermore, it inhibits the alpha3beta4 current in a reversible, noncompetitive, voltage-, and use-dependent manner, a behavior compatible with open-channel blockade. In fura-2-loaded single chromaffin cells, the peptide reduced the [Ca2+]c signal and the total release of catecholamines elicited by ACh; however, catestatin did not modify the kinetics or the last step of the exocytotic process. Our results suggest that catestatin might play an autocrine regulatory role in neuroendocrine secretion through its interaction with different native nAChR subtypes; the extent of receptor blockade by the peptide could be acutely regulated by the intensity and duration of the presynaptic stimulus. PMID- 11784783 TI - Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. AB - Selective blockers of the norepinephrine transporter (NET) inhibit dopamine uptake in the prefrontal cortex. This suggests that dopamine in this region is normally cleared by the somewhat promiscuous NET. We have tested this hypothesis by comparing the effects of inhibitors selective for the three monoamine transporters with those of a nonspecific inhibitor, cocaine, on uptake of 3H dopamine into synaptosomes from frontal cortex, caudate nucleus, and nucleus accumbens from wild-type, NET, and dopamine transporter (DAT) knock-out mice. Dopamine uptake was inhibited by cocaine and nisoxetine, but not by GBR12909, in frontal cortex synaptosomes from wild-type or DAT knock-out mice. At transporter specific concentrations, nisoxetine and GBR12909 failed to block dopamine uptake into frontal cortex synaptosomes from NET knock-out mice. The efficacy of cocaine at the highest dose (1 mm) was normal in DAT knock-out mice but reduced by 70% in NET knock-out mice. Nisoxetine inhibited dopamine uptake by 20% in caudate and nucleus accumbens synaptosomes from wild-type and DAT knock-out mice but had no effect in those from NET knock-out mice. Cocaine failed to block dopamine uptake into caudate or nucleus accumbens synaptosomes from DAT knock-out mice. Cocaine and GBR12909 each inhibited dopamine uptake into caudate synaptosomes from NET knock-out mice, but cocaine effectiveness was reduced in the case of nucleus accumbens synaptosomes. Thus, whereas dopamine uptake in caudate and nucleus accumbens depends primarily on the DAT, dopamine uptake in frontal cortex depends primarily on the NET. These data underscore the fact that which transporter clears dopamine from a given region depends on both the affinities and the local densities of the transporters. PMID- 11784784 TI - Differential inhibition of T-type calcium channels by neuroleptics. AB - T-type calcium channels play critical roles in cellular excitability and have been implicated in the pathogenesis of a variety of neurological disorders including epilepsy. Although there have been reports that certain neuroleptics that primarily target D2 dopamine receptors and are used to treat psychoses may also interact with T-type Ca channels, there has been no systematic examination of this phenomenon. In the present paper we provide a detailed analysis of the effects of several widely used neuroleptic agents on a family of exogenously expressed neuronal T-type Ca channels (alpha1G, alpha1H, and alpha1I subtypes). Among the neuroleptics tested, the diphenylbutylpiperidines pimozide and penfluridol were the most potent T-type channel blockers with Kd values (approximately 30-50 nm and approximately 70-100 nm, respectively), in the range of their antagonism of the D2 dopamine receptor. In contrast, the butyrophenone haloperidol was approximately 12- to 20-fold less potent at blocking the various T-type Ca channels. The diphenyldiperazine flunarizine was also less potent compared with the diphenylbutylpiperadines and preferentially blocked alpha1G and alpha1I T-type channels compared with alpha1H. The various neuroleptics did not significantly affect T-type channel activation or kinetic properties, although they shifted steady-state inactivation profiles to more negative values, indicating that these agents preferentially bind to channel inactivated states. Overall, our findings indicate that T-type Ca channels are potently blocked by a subset of neuroleptic agents and suggest that the action of these drugs on T-type Ca channels may significantly contribute to their therapeutic efficacy. PMID- 11784785 TI - Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. AB - Urocortin and urocortin II are members of the corticotropin-releasing hormone (CRH) family of neuropeptides that function to regulate stress responses. Two high-affinity G-protein-coupled receptors have been identified that bind CRH and/or urocortin I and II, designated CRHR1 and CRHR2, both of which are present in hippocampal regions of mammalian brain. The hippocampus plays an important role in regulating stress responses and is a brain region in which neurons are vulnerable during disease and stress conditions, including cerebral ischemia, Alzheimer's disease, and anxiety disorders. Here we report that urocortin exerts a potent protective action in cultured rat hippocampal neurons with concentrations in the range of 0.5-5.0 pm, increasing the resistance of the cells to oxidative (amyloid beta-peptide, 4-hydroxynonenal, ferrous sulfate) and excitotoxic (glutamate) insults. We observed that urocortin is 10-fold more potent than CRH in protecting hippocampal neurons from insult, whereas urocortin II is ineffective. RT-PCR and sequencing analyses revealed the presence of both CRHR1 and CRHR2 in the hippocampal cultures, with CRHR1 being expressed at much higher levels than CRHR2. Using subtype-selective CRH receptor antagonists, we provide evidence that the neuroprotective effect of exogenously added urocortin is mediated by CRHR1. Furthermore, we provide evidence that the signaling pathway that mediates the neuroprotective effect of urocortin involves cAMP-dependent protein kinase, protein kinase C, and mitogen-activated protein kinase. This is the first demonstration of a biological activity of urocortin in hippocampal neurons, suggesting a role for the peptide in adaptive responses of hippocampal neurons to potentially lethal oxidative and excitotoxic insults. PMID- 11784786 TI - Molecular phenotyping of retinal ganglion cells. AB - Classifying all of the ganglion cells in the mammalian retina has long been a goal of anatomists, physiologists, and cell biologists. The rabbit retinal ganglion cell layer was phenotyped using intrinsic small molecule signals (aspartate, glutamate, glycine, glutamine, GABA, and taurine) and glutamate receptor-gated 1-amino-4-guanidobutane excitation signals as the clustering dimensions for formal classification. Intrinsic signals alone yielded 7 ganglion cell superclasses and 1 amacrine cell superclass; the addition of excitation signals ultimately resolved 14 natural ganglion cell classes and 3 amacrine cell classes. Ganglion cells comprise two-thirds to three-quarters of the cells in the ganglion cell layer and exhibited distinct metabolic, coupling, and excitation phenotypes, as well as characteristic sizes, population fractions, and patterns. Metabolic signatures (mixtures of glutamate, aspartate, glutamine, and GABA) chemically discriminated ganglion from amacrine cells. Coupling signatures reflected heterologous coupling states across ganglion cells: (1) uncoupled, (2) coupled to GABAergic amacrine cells, and (3) coupled to glycinergic amacrine cells. Excitation signatures reflected differential channel permeation rates across classes after AMPA activation. Extraction of unique size and patterning features from the data sets further validated the robustness of the classification. Because the classifications were explicitly blinded to structure, this is strong evidence that molecular phenotype classes are natural classes. Correspondences of molecular phenotype classes to functional classes were inferred from size, coupling, encounter, and physiological attributes. Ganglion cell classes display markedly different ionotropic drives, which may partly explain the physiological brisk-sluggish spectrum of ganglion cell spiking patterns. PMID- 11784787 TI - Mutation of Drosophila homer disrupts control of locomotor activity and behavioral plasticity. AB - Homer proteins have been proposed to play a role in synaptogenesis, synapse function, receptor trafficking, and axon pathfinding. Here we report the isolation and characterization of the Drosophila gene homer, the single Homer related gene in fly. Using anti-Homer antibody we show that Homer is expressed in a broad range of tissues but is highly enriched in the CNS. Similarly to its mammalian counterpart, the Drosophila Homer localizes to the dendrites and the endoplasmic reticulum (ER). This subcellular distribution is dependent on an intact Enabled/Vasp homology 1 domain, suggesting that Homer must bind to one or more of its partners for proper localization. We have created a mutation of homer and show that flies homozygous for this mutation are viable and show coordinated locomotion, suggesting that Homer is not essential for basic neurotransmission. However, we found that homer mutants display defects in behavioral plasticity and the control of locomotor activity. Our results argue that in the CNS, Homer related proteins operate in the ER and in dendrites to regulate the development and function of neural networks underlying locomotor control and behavioral plasticity. PMID- 11784788 TI - Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. AB - The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the OB. Specifically, these stem cells do not derive from the migratory neuroblasts coming from the SVZ. Interestingly, stem cells isolated from the proximal RE generate significantly more oligodendrocytes, and those from the distal RE proliferate significantly more slowly than stem cells derived from the SVZ and other RE regions. These findings demonstrate that stem cells are not confined to the forebrain periventricular region and indicate that stem cells endowed with different functional characteristics occur at different levels of the SVZ-RE pathway. PMID- 11784789 TI - Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. AB - Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia. To address this question, we studied neuropathological and behavioral consequences of single versus repetitive mild TBI (mTBI) in transgenic (Tg) mice (Tg2576) that express mutant human Abeta precursor protein, and we demonstrate elevated brain Abeta levels and increased Abeta deposition. Nine-month-old Tg2576 and wild-type mice were subjected to single (n = 15) or repetitive (n = 39) mTBI or sham treatment (n = 37). At 2 d and 9 and 16 weeks after treatment, we assessed brain Abeta deposits and levels in addition to brain and urine isoprostanes generated by lipid peroxidation in these mice. A subset of mice also was studied behaviorally at 16 weeks after injury. Repetitive but not single mTBI increased Abeta deposition as well as levels of Abeta and isoprostanes only in Tg mice, and repetitive mTBI alone induced cognitive impairments but no motor deficits in these mice. This is the first experimental evidence linking TBI to mechanisms of AD by showing that repetitive TBI accelerates brain Abeta accumulation and oxidative stress, which we suggest could work synergistically to promote the onset or drive the progression of AD. Additional insights into the role of TBI in mechanisms of AD pathobiology could lead to strategies for reducing the risk of AD associated with previous episodes of brain trauma and for preventing progressive brain amyloidosis in AD patients. PMID- 11784790 TI - Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. AB - In the premature infant, hypoxic-ischemic damage to the cerebral white matter [periventricular leukomalacia (PVL)] is a common and leading cause of brain injury that often results in chronic neurologic disability from cerebral palsy. The cellular basis for the propensity of white matter injury to occur in the developing brain and the greater resistance of the adult white matter to similar injury remains unknown. By using a neonatal rat model of hypoxic-ischemic injury, we found that the mechanism of perinatal white matter injury involved maturation dependent vulnerability in the oligodendroctye (OL) lineage. The timing of appearance of late OL progenitors was the major developmental factor that accounted for the susceptibility of the neonatal white matter to injury. Late OL progenitors were the major OL lineage stage killed by apoptosis, whereas early OL progenitors and more mature OLs were highly resistant. The density of pyknotic late OL progenitors was significantly increased in the ischemic hemisphere (67 +/ 31 cells/mm2) versus the control hemisphere (2.2 +/- 0.4 cells/mm2; mean +/- SEM; p = 0.05), which resulted in the death of 72 +/- 6% of this OL stage. Surviving late OL progenitors displayed a reactive response in which an increase in cell density was accompanied by accelerated maturation to a P27/kip1-positive oligodendrocyte. Because we showed recently that late OL progenitors populate human cerebral white matter during the high risk period for PVL (Back et al., 2001), maturation-dependent vulnerability of OL progenitors to hypoxia-ischemia may underlie the selective vulnerability to PVL of the white matter in the premature infant. PMID- 11784791 TI - The community effect and Purkinje cell migration in the cerebellar cortex: analysis of scrambler chimeric mice. AB - The Disabled-1 protein in mouse is known to be an intercellular signaling component of the Reelin molecular pathway that subserves neuronal migration in several structures in the brain and spinal cord. The scrambler mutant mouse, which is phenotypically identical to the reeler mouse, is due to a mutation in the disabled-1 gene (Howell et al., 1997; Sheldon et al., 1997). The Purkinje cells of the cerebellum express Disabled-1 and experience a massive failure of migration in the scrambler mutant mouse (Howell et al., 1997; Sheldon et al., 1997; Gallagher et al., 1998; Rice et al., 1998). We sought to define the developmental basis of this mutation by studying the Purkinje cell population in experimental mouse aggregation chimeras using a cell marker that permitted the identification of neurons derived from the mutant lineage. We found that a genetically normal component to the environment cannot assist scrambler mutant Purkinje cells in the migratory process. However, the presence of a mutant component to the environment can cause the ectopia of wild-type Purkinje cells. There appears to be a linear relationship between the percentage of the cerebellum that is genetically mutant and the number of wild-type Purkinje cells that express a mutant phenotype. These studies point to the interplay between cell-intrinsic and cell-extrinsic properties in the migration of neurons to form laminated structures during CNS development. PMID- 11784792 TI - Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse. AB - The semaphorins are a large protein family that is involved in the patterning of neuronal connections in the developing nervous system of both vertebrates and invertebrates. The chemorepulsive axon guidance signal Semaphorin 3A (Sema3A) induces the depolymerization of actin filaments and the collapse of sensory growth cones by activating a receptor complex that contains a plexin as the signal-transducing subunit. Here we show that, of a large number of GTPases tested, only Rnd1 and RhoD bind the cytoplasmic domain of Plexin-A1. Recruitment of active Rnd1 is sufficient to trigger signaling by Plexin-A1, even in the absence of Sema3A, and initiates cytoskeletal collapse by activating its cytoplasmic domain. RhoD, in contrast, blocks Plexin-A1 activation by Rnd1 and repulsion of sympathetic axons by Sema3A. Thus, the antagonism of two GTPases regulates the activity of the Sema3A receptor, and activation by Rnd1 appears to be an essential step in signaling by Plexin-A1. PMID- 11784793 TI - ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. AB - Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons of the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated ERK activation by peripheral inflammation and its involvement in regulating gene expression in the spinal cord and in contributing to inflammatory pain hypersensitivity. Injection of complete Freund's adjuvant (CFA) into a hindpaw produced a persistent inflammation and a sustained ERK activation in neurons in the superficial layers (laminae I-IIo) of the dorsal horn. CFA also induced an upregulation of prodynorphin and neurokinin-1 (NK-1) in dorsal horn neurons, which was suppressed by intrathecal delivery of the MEK (MAP kinase kinase) inhibitor U0126. CFA-induced phospho-ERK primarily colocalized with prodynorphin and NK-1 in superficial dorsal horn neurons. Although intrathecal injection of U0126 did not affect basal pain sensitivity, it did attenuate both the establishment and maintenance of persistent inflammatory heat and mechanical hypersensitivity. Activation of the ERK pathway in a subset of nociceptive spinal neurons contributes, therefore, to persistent pain hypersensitivity, possibly via transcriptional regulation of genes, such as prodynorphin and NK-1. PMID- 11784794 TI - Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. AB - Postnatal neurogenesis can be modulated after brain injury, but the role of the attendant expression of inflammatory mediators in such responses remains to be determined. Here we report that transgenically directed production of interleukin 6 (IL-6) by astroglia decreased overall neurogenesis by 63% in the hippocampal dentate gyrus of young adult transgenic mice. The proliferation, survival, and differentiation of neural progenitor cells labeled with the thymidine analog bromodeoxyuridine were all reduced in the granule cell layer of these mice, whereas their distribution and gliogenesis appeared normal. These effects were not a consequence of general toxicity of the IL-6 transgene, because they were manifested in the absence of neuronal death and of major changes in glial cell number and morphology. These findings suggest that long-term exposure of the brain to proinflammatory mediators such as IL-6, as is seen in certain degenerative disorders and infections, can interfere with adult neurogenesis. PMID- 11784795 TI - Postnatal development of membrane excitability in taste cells of the mouse vallate papilla. AB - The mammalian peripheral taste system undergoes functional changes during postnatal development. These changes could reflect age-dependent alterations in the membrane properties of taste cells, which use a vast array of ion channels for transduction mechanisms. Yet, scarce information is available on the membrane events in developing taste cells. We have addressed this issue by studying voltage-dependent Na+, K+, and Cl- currents (I(Na), I(K), and I(Cl), respectively) in a subset of taste cells (the so-called "Na/OUT" cells, which are electrically excitable and thought to be sensory) from mouse vallate papilla. Voltage-dependent currents play a key role during taste transduction, especially in the generation of action potentials. Patch-clamp recordings revealed that I(Na), I(K), and I(Cl) were expressed early in postnatal development. However, only I(K) and I(Cl) densities increased significantly in developing Na/OUT cells. Consistent with the rise of I(K) density, we found that action potential waveform changed markedly, with an increased speed of repolarization that was accompanied by an enhanced capability of repetitive firing. In addition to membrane excitability changes in putative sensory cells, we observed a concomitant increase in the occurrence of glia-like taste cells (the so called "leaky" cells) among patched cells. Leaky cells are likely involved in dissipating the increase of extracellular K+ during action potential discharge in chemosensory cells. Thus, developing taste cells of the mouse vallate papilla undergo a significant electrophysiological maturation and diversification. These functional changes may have a profound impact on the transduction capabilities of taste buds during development. PMID- 11784796 TI - Trophic factor-induced excitatory synaptogenesis involves postsynaptic modulation of nicotinic acetylcholine receptors. AB - Neurotrophic factors have well established roles in neuronal development, although their precise involvement in synapse formation and plasticity is yet to be fully determined. Using soma-soma synapses between identified Lymnaea neurons, we have shown recently that trophic factors are required for excitatory but not inhibitory synapse formation. However, neither the precise site (presynaptic versus postsynaptic cell) nor the underlying mechanisms have yet been defined. In the present study, synapse formation between the presynaptic cell visceral dorsal 4 (VD4) and its postsynaptic partner right pedal dorsal 1 (RPeD1) was examined to define the cellular mechanisms mediating trophic factor-induced excitatory synaptogenesis in cell culture. When paired in a soma-soma configuration in the presence of defined media (DM, nonproteinacious), mutually inhibitory synapses were appropriately reconstructed between VD4 and RPeD1. However, when cells were paired in the presence of increasing concentrations of Lymnaea brain-conditioned medium (CM), a biphasic synapse (initial excitatory synaptic component followed by inhibition) developed. The CM-induced excitatory synapse formation required trophic factor-mediated activation of receptor tyrosine kinases in the postsynaptic cell, RPeD1, and a concomitant modulation of existing postsynaptic nicotinic acetylcholine receptors (nAChRs). Specifically, when RPeD1 was isolated in DM, exogenously applied ACh induced a hyperpolarizing response that was sensitive to the AChR antagonist methyllycaconitine (MLA). In contrast, a single RPeD1 isolated in CM exhibited a biphasic response to exogenously applied ACh. The initial depolarizing phase of the biphasic response was sensitive to both mecamylamine and hexamethonium chloride, whereas the hyperpolarizing phase was blocked by MLA. In soma-soma-paired neurons, the VD4-induced synaptic responses in RPeD1 were sensitive to the cholinergic antagonists in a concentration range similar to that used to block cholinergic responses in single RPeD1 cells. Therefore, the modulation of postsynaptic nAChRs was sufficient to account for the trophic factor-induced excitatory synaptogenesis. This study thus provides the first direct evidence that trophic factors act postsynaptically to promote excitatory synapse formation. PMID- 11784797 TI - Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. AB - APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. We have previously reported neuron loss in the hippocampal CA1 region of 14- to 18-month-old APP23 mice. In contrast, no neuron loss was found in neocortex. In the present study we have reinvestigated neocortical neuron numbers in adult and aged APP23 mice. Surprisingly, results revealed that 8-month-old APP23 mice have 13 and 14% more neocortical neurons compared with 8-month-old wild-type and 27-month-old APP23 mice, respectively. In 27-month-old APP23 mice we found an inverse correlation between amyloid load and neuron number. These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. Supporting this notion, we found more neurons with a necrotic apoptotic phenotype in the neocortex of 24-month-old APP23 mice compared with age matched wild-type mice. Stimulated by recent reports that demonstrated neurogenesis after targeted neuron death in the mouse neocortex, we have also examined neurogenesis in APP23 mice. Strikingly, we found a fourfold to sixfold increase in newly produced cells in 24-month-old APP23 mice compared with both age-matched wild-type mice and young APP23 transgenic mice. However, subsequent cellular phenotyping revealed that none of the newly generated cells in neocortex had a neuronal phenotype. The majority were microglial and to a lesser extent astroglial cells. We conclude that cerebral amyloidosis in APP23 mice causes a modest neuron loss in neocortex and induces marked gliogenesis. PMID- 11784798 TI - Dissociable human perirhinal, hippocampal, and parahippocampal roles during verbal encoding. AB - The precise contribution of perirhinal cortex to human episodic memory is uncertain. Human intracranial recordings highlight a role in successful episodic memory encoding, but encoding-related perirhinal activation has not been observed with functional imaging. By adapting functional magnetic resonance imaging scanning parameters to maximize sensitivity to medial temporal lobe activity, we demonstrate that left perirhinal and hippocampal responses during word list encoding are greater for subsequently recalled than forgotten words. Although perirhinal responses predict memory for all words, successful encoding of initial words in a list, demonstrating a primacy effect, is associated with parahippocampal and anterior hippocampal activation. We conclude that perirhinal cortex and hippocampus participate in successful memory encoding. Encoding related parahippocampal and anterior hippocampal responses for initial, remembered words most likely reflects enhanced attentional orienting to these positionally distinctive items. PMID- 11784799 TI - Dual cholinergic control of fast-spiking interneurons in the neostriatum. AB - GABAergic interneurons appear to play a fundamental role in the functioning of the neostriatum by modulating the spiking of striatal projection neurons with great efficacy. The powerful and strongly divergent output of the GABAergic interneurons neurons suggests that modulation of their activity may be particularly effective at controlling the functioning of the entire neostriatal circuitry. Acetylcholine is one of the main modulators of striatal functioning. The effects of acetylcholine on fast-spiking (FS) GABAergic interneurons were studied with whole-cell recording in an in vitro slice preparation. Acetylcholine exerted two distinct effects on fast-spiking interneurons. Acetylcholine directly depolarized FS interneurons by acting on nondesensitizing soma-dendritic nicotinic receptors. In addition, acetylcholine attenuated the GABAergic inhibition of projection neurons by fast-spiking interneurons through activation of presynaptic muscarinic receptors. It is suggested that the nicotinic excitation of FS interneurons may play an important role in translating the effect of the brief behaviorally contingent cessation of firing of the tonically active cholinergic interneurons to the output neurons of the neostriatum. In contrast, the muscarinic presynaptic inhibitory mechanism may be engaged primarily during longer-lasting elevations of extracellular acetylcholine levels. PMID- 11784800 TI - Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. AB - Tumor necrosis factor-alpha (TNF) appears as a key player at both central and peripheral terminals in early degenerative pathology and pain behavior after peripheral nerve injury. Recent studies suggest that TNF may be axonally transported and thereby contribute to these central and peripheral actions. To characterize this transport, we used a double ligation (DL) procedure that distinguishes between anterograde and retrograde flow to visualize the axonal transport of endogenous TNF compared with the neurotrophin nerve growth factor (NGF) and to the neuropeptide calcitonin gene-related peptide (CGRP). In the intact nerve, TNF and CGRP immunoreactivity predominantly accumulated proximal to the DL (anterograde transport), whereas NGF displayed exclusive retrograde transport. At 20 hr after chronic constrictive injury (CCI), the anterograde transport of TNF and CGRP to the nerve injury site was dramatically increased. The results were corroborated by the analysis of axonal transport of exogenously applied 125I-TNF and 125I-NGF. After intraneural injection, 125I-TNF accumulated proximally to a DL, suggesting anterograde transport. In the unligated nerve, 125I-TNF was specifically transported anterogradely to the innervated muscle but not to skin. After CCI, 125I-TNF accumulated proximally to the peripheral nerve injury site, and endogenous TNF was exclusively increased in medium-sized and large dorsal root ganglion (DRG) neurons, suggesting that DRG neurons are a major contributing source of increased TNF traffic in the injured sciatic nerve. Our results suggest that anterograde transport of TNF plays a major role in the early neuronal response to peripheral nerve injury at sites distal to the cell body. PMID- 11784801 TI - Cerebellar involvement in response reassignment rather than attention. AB - A number of functional hypotheses have recently been advanced to account for how the cerebellum may contribute to cognition. Neuropsychological studies suggest the cerebellum is involved in switching attentional set. We present evidence that fails to support this hypothesis. Rather, we propose that in such tasks, the cerebellum is involved with the remapping of response alternatives to different types of stimuli. In our experiment, participants fixated on the center of a screen onto which a random presentation of four visual stimuli was presented. The stimuli were grouped along two dimensions (color: red square or blue square; shape: white circle or white triangle). Participants were instructed to respond with a button press only to presented stimuli for a particular dimension (e.g., red squares), to switch between two dimensions (where the target on the attended dimension served both as a signal for a response and as an indicator to shift attention to the other dimension), or to switch attention between two dimensions but make an overt response only to targets on one of the dimensions. Using functional imaging, we identify areas of lateral cerebellar cortex that are recruited when subjects must reassign motor responses to different stimuli. Furthermore, we demonstrate that switching of attention between dimensions without a motor response does not produce stronger activation within the cerebellum compared with conditions involving response and attention to a single dimension. These results suggest the cerebellum is involved in response reassignment. PMID- 11784802 TI - Functional connectivity of human premotor and motor cortex explored with repetitive transcranial magnetic stimulation. AB - Connections between the premotor cortex and the primary motor cortex are dense and are important in the visual guidance of arm movements. We have shown previously that it is possible to engage these connections in humans and to measure the net amount of inhibition/facilitation from premotor to motor cortex using single-pulse transcranial magnetic stimulation (TMS). The aim of this study was to test whether premotor activation can affect the excitability of circuits within the primary motor cortex (M1) itself. Repetitive TMS (rTMS), which is known to produce effects that outlast the train at the site of stimulation, was given for 20 min at 1 Hz over premotor, primary motor, and sensory areas of cortex at an intensity of 80% of the active motor threshold for the motor hand area. The excitability of some corticocortical connections in M1 was probed by using paired-pulse testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) with a coil placed over the motor cortex hand area. rTMS over the premotor cortex, but not other areas, changed the time course of the ICI/ICF for up to 1 hr afterward without affecting motor thresholds or motor-evoked potential recruitment. The cortical silent period was also shortened. The implication is that rTMS at a site distant from the motor cortex can change the excitability of circuits intrinsic to the motor cortex. PMID- 11784803 TI - Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus. AB - Although inactivation of the subthalamic nucleus (STN) has beneficial effects on motor symptoms of parkinsonism, little is known of possible actions on nonmotor symptoms of cognition or mood. Here, we used several forms of converging evidence to show that STN lesions can enhance behavioral motivation. Thus, bilateral fiber sparing lesions of the STN in rats reduced the time required to eat a standard number of food reward pellets, without affecting food intake, and altered performance on a number of behavioral measures consistent with enhanced motivation for food. Thus, STN-lesioned rats showed greater levels of locomotor activity conditioned to food presentation, enhanced control over responding by food-related conditioned reinforcers, and a higher breaking point associated with elevated rate of lever press under a progressive ratio schedule of reinforcement. These results reveal a new functional role schedule for STN, possibly because of its involvement in ventral, as well as dorsal, striatal circuitry and are relevant to the therapeutic effects of STN stimulation in Parkinson's disease. PMID- 11784804 TI - Lid restraint evokes two types of motor adaptation. AB - Unilateral reduction in eyelid motility produced two modes of blink adaptation in humans. The first adaptive modification affected both eyelids. Stimulation of the supraorbital branch of the trigeminal nerve (SO) ipsilateral to the upper eyelid with reduced motility evoked bilateral, hyperexcitable reflex blinks, whereas contralateral SO stimulation elicited normally excitable blinks bilaterally. The probability of blink oscillations evoked by stimulation of the ipsilateral SO also increased with a reduction in lid motility. The increased probability of blink oscillations correlated with the enhanced trigeminal reflex blink excitability. Thus, the trigeminal complex ipsilateral to the restrained eyelid coordinated an increase in excitability and blink oscillations independent of the eyelid experiencing reduced motility. The second type of modification appeared only in the eyelid experiencing reduced motility. When tested immediately after removing lid restraint, blink amplitude increased in this eyelid relative to the normal eyelid regardless of the stimulated SO. A patient with seventh nerve palsy exhibited the same two patterns of blink adaptation. These results were consistent with two forms of adaptation, presumably because unilateral lid restraint produced two error signals. The corneal irritation caused by reduced blink amplitude generated abnormal corneal inputs. The difference between proprioceptive feedback from the blink and expected blink magnitude signaled an error in blink amplitude. The corneal irritation appeared to drive an adaptive process organized through the trigeminal complex, whereas the proprioceptive error signal drove an adaptive process involving just the motoneurons controlling the restrained eyelid. PMID- 11784805 TI - Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. AB - Considerable efforts have been made to identify changes of brain synaptic plasticity associated with fear conditioning. However, for both clinical applications and our fundamental understanding of memory processes, it appears also necessary to investigate synaptic plasticity related to extinction. We previously showed that extinction of freezing to a tone conditioned stimulus (CS; previously paired with footshock) in mice results in a sequence of depression and potentiation of synaptic efficacy in the medial prefrontal cortex (mPFC). These data as well as those from lesion studies suggest that the direction of changes in prefrontal synaptic plasticity may modulate extinction of learned fear. To test this, we analyzed the effects of low-frequency stimulation (LFS) and high frequency stimulation (HFS) of the mediodorsal thalamic nucleus, known to induce prefrontal long-term depression (LTD) and potentiation (LTP), respectively, on extinction. We found that maintenance of the depression phase, using thalamic LFS, was associated with resistance to extinction. Thalamic HFS applied before extinction testing had no effect on the rate of extinction. However, 1 week follow-up tests revealed that the memory of extinction was intact in these mice (with prefrontal LTP) and in control mice displaying prefrontal LTP-like changes, whereas control mice that did not exhibit such changes displayed a return of freezing to the CS. The results suggest that after extinction the lack of depression-LTP-like conversion sequence in the mPFC synaptic efficacy may profoundly alter the process of consolidation. PMID- 11784806 TI - Redundancy reduction and sustained firing with stochastic depressing synapses. AB - Many synapses in the CNS transmit only a fraction of the action potentials that reach them. Although unreliable, such synapses do not transmit completely randomly, because the probability of transmission depends on the recent history of synaptic activity. We examine how a variety of spike trains, including examples recorded from area V1 of monkeys freely viewing natural scenes, are transmitted through a realistic model synapse with activity-dependent depression arising from vesicle depletion or postrelease refractoriness. The resulting sequences of transmitted spikes are significantly less correlated, and hence less redundant, than the presynaptic spike trains that generate them. The spike trains we analyze, which are typical of those recorded in a variety of brain regions, have positive autocorrelations because of the occurrence of variable length periods of sustained firing at approximately constant rates. Sustained firing may, at first, seem inconsistent with input from depressing synapses. We show, however, that such a pattern of activity can arise if the postsynaptic neuron is driven by a fixed population of direct, "feedforward" inputs accompanied by a variable number of delayed, "reverberatory" inputs. This leads to a prediction for the number and latency distribution of the inputs that typically drive a cortical neuron. PMID- 11784807 TI - Effects of transient focal inactivation of the basal ganglia in parkinsonian primates. AB - Ablative and chronic stimulation procedures targeting the internal pallidum (GPi) and the subthalamic nucleus (STN) have led to major advancements in the treatment of Parkinson's disease and other movement disorders. Although these procedures have evolved to primarily target the posterior ventrolateral sensorimotor portion of GPi and to less selectively target STN, centrally, the ideal targets within these structures remain to be fully established. In this study, we sought to identify the optimal targeting sites in GPi and STN for reversal of parkinsonian signs through a series of reversible injections of the GABA(A) agonist muscimol in these nuclei in parkinsonian primates. Akinesia and bradykinesia were strongly ameliorated by discrete inactivation within the centromedial extent of the sensorimotor territory in GPi and the lateral portion of the sensorimotor territory in STN. This suggests that akinesia and bradykinesia might, in fact, originate from abnormalities in the same, or at least overlapping, motor circuits in the parkinsonian state. Inactivation of areas outside of the motor territories did not improve parkinsonism but induced circling and behavioral abnormalities. The segregation of basal ganglia-thalamocortical circuits appears to be therefore maintained, at least to a large extent, in the parkinsonian state. These results underscore that inactivation of discrete regions in the central territory of GPi and the lateral portion of STN are sufficient to ameliorate parkinsonian motor signs and that extension of lesions into nonmotor territories may be deleterious. Surgical outcomes might therefore be optimized by placing more discrete lesions and by restricting the extent of chronic stimulation. PMID- 11784808 TI - Predictions specify reactive control of individual digits in manipulation. AB - When humans proactively manipulate objects, the applied fingertip forces primarily depend on feedforward, predictive neural control mechanisms that depend on internal representations of the physical properties of the objects. Here we investigate whether predictions of object properties also control fingertip forces that subjects generate reactively. We analyzed fingertip forces reactively supporting grasp stability in a restraining task that engaged two fingers. Each finger contacted a plate mounted on a separate torque motor, and, at unpredictable times, both plates were loaded simultaneously with forces tangential to the plates or just one of the plates was loaded. Thus, the apparatus acted as though the plates were mechanically linked or as though they were two independent objects. In different test series, each with a predominant behavior of the apparatus and with interspersed catch trials, we showed that the reactive responses clearly reflected the predominant behavior of the apparatus. Whether subject performed the task with one hand or bimanually, appropriate reactive fingertip forces developed when predominantly both contact plates were loaded or just one of the plates was loaded. When a finger was unexpectedly loaded during a catch trial, a weak initial reactive response was triggered, but the effective force development was delayed by approximately 100 msec. We conclude that the predicted physical properties of an object not only control fingertip forces during proactive but also in reactive manipulative tasks. Specifically, the automatic reactive responses reflect predictions at the level of individual digits as to the mechanical linkage of items contacted by the fingertips in manipulation. PMID- 11784809 TI - Hippocampal pyramidal cell-interneuron spike transmission is frequency dependent and responsible for place modulation of interneuron discharge. AB - The interplay between principal cells and interneurons plays an important role in timing the activity of individual cells. We investigated the influence of single hippocampal CA1 pyramidal cells on putative interneurons. The activity of CA1 pyramidal cells was controlled intracellularly by current injection, and the activity of neighboring interneurons was recorded extracellularly in the urethane anesthetized rat. Spike transmission probability between monosynaptically connected pyramidal cell-interneuron pairs was frequency dependent and highest between 5 and 25 Hz. In the awake animal, interneurons were found that had place modulated firing rates, with place maps similar to their presynaptic pyramidal neuron. Thus, single pyramidal neurons can effectively determine the firing patterns of their interneuron targets. PMID- 11784810 TI - "Keeping on track": firing of hippocampal neurons during delayed-nonmatch-to sample performance. AB - Hippocampal neurons that encode critical events during a delayed-nonmatch-to sample (DNMS) task were proposed to have functional topography as demonstrated by Hampson et al. (1999b). Functional cell types (FCTs) that encode similar task features were located within alternating transverse segments along the hippocampal longitudinal axis. On this basis, Redish et al. (2001) suggested that firing of populations of CA1 neurons recorded from the same hippocampal locations in animals running on linear or curvilinear tracks should be spatially and temporally correlated; however, they failed to find such correlations. The current study addresses the issues raised by Redish et al. (2001). Initially we found that modeling of simulated place fields revealed absences in temporal correlations in the study by Redish et al. (2001) that should have been present given the reported spatial correlations. In addition, the correlation methods used by those investigators failed to detect robust but transient event-related cross-correlations between FCTs in the DNMS task. Furthermore, demonstration of such transient, short-latency correlated firing between similar CA3 and CA1 FCTs corroborated the anatomic scheme proposed by Hampson et al. (1999b) and reaffirmed the potential existence of a functional topography within hippocampus. PMID- 11784811 TI - Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels. AB - The muscarinic-regulated potassium current (M-current), formed by the heteromeric assembly of subunits encoded by the KCNQ2 and KCNQ3 genes, is a primary regulator of neuronal excitability; this regulation is accomplished by impeding repetitive firing and causing spike-frequency adaptation. Mutations in KCNQ2 or KCNQ3 cause benign familial neonatal convulsions (BFNC), a rare autosomal-dominant generalized epilepsy of newborns, by reducing the maximal current carried by the M-channels without affecting ion selectivity or gating properties. Here we show that KCNQ2/KCNQ3 channels carrying a novel BFNC-causing mutation leading to an arginine to tryptophan substitution in the voltage-sensing S4 domain of KCNQ2 subunits (R214W) displayed slower opening and faster closing kinetics and a decreased voltage sensitivity with no concomitant changes in maximal current or plasma membrane expression. These results suggest that mutation-induced gating alterations of the M-current may cause epilepsy in neonates. PMID- 11784812 TI - The septohippocampal system participates in general anesthesia. AB - How the brain mediates general anesthesia is not known. We report that two interconnected structures in the forebrain, the medial septum and the hippocampus, participate in maintaining awareness and movements during general anesthesia. In the awake, freely behaving rat, inactivation of the medial septum or the hippocampus by local injection of a GABA(A) receptor agonist, muscimol, decreased the dose of a general anesthetic needed to induce a loss of the tail pinch response or a loss of righting reflex. Septohippocampal inactivation also suppressed the behavioral hyperactivity or the delirium stage associated with general anesthesia. An increase and decrease of 30-50 Hz (gamma) waves in the hippocampus correlated with an increase and decrease in behavioral activity, respectively. Similar results were found for both volatile (halothane and isoflurane) and nonvolatile (propofol and pentobarbital) anesthetics. We conclude that the behavioral hyperactivity induced by a general anesthetic is mediated in part by the septohippocampal system, and that depression of the septohippocampal system increases the potency of a general anesthetic. It is suggested that more potent general anesthetics or adjuvants may be developed by maximizing the pharmacological depression of the septohippocampal system. PMID- 11784814 TI - Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington's disease gene. AB - The extracellular fluid of the striatum contains a high level of ascorbate, an antioxidant vitamin known to play a key role in behavioral activation. We assessed the extracellular dynamics of ascorbate in R6/2 mice engineered to express the gene for Huntington's disease (HD), an autosomal dominant condition characterized by the loss of striatal neurons. Slow-scan voltammetry was used to measure striatal ascorbate during anesthesia and subsequent behavioral recovery. Although both the HD mice and their littermate controls had comparable ascorbate levels during anesthesia, the gradual return of behavioral activation over the next 120 min led to dramatically different ascorbate responses: a progressive increase in controls and a 25-50% decline in HD mice. In contrast, 3,4 dihydroxyphenylacetic acid, a major dopamine metabolite, showed no group differences. Behaviorally, HD mice were less active overall than controls and showed a relatively restricted range of spontaneous movements. Both the ascorbate and behavioral deficits were evident in 6-week-old HD mice and persisted in all subsequent test sessions through 10 weeks of age. Collectively, although these results are consistent with inadequate antioxidant protection in the HD striatum, they indicate that the ascorbate deficit is confined to periods of behavioral activation. PMID- 11784813 TI - Experience modifies olfactory acuity: acetylcholine-dependent learning decreases behavioral generalization between similar odorants. AB - Perceptual learning has been demonstrated in several thalamocortical sensory systems wherein experience enhances sensory acuity for trained stimuli. This perceptual learning is believed to be dependent on changes in sensory cortical receptive fields. Sensory experience and learning also modifies receptive fields and neural response patterns in the mammalian olfactory system; however, to date there has been little reported evidence of learned changes in behavioral olfactory acuity. The present report used a bradycardial orienting response and cross-habituation paradigm that allowed assessment of behavioral discrimination of nearly novel odorants, and then used the same paradigm to examine odorant discrimination after associative olfactory conditioning with similar or dissimilar odorants. The results demonstrate that associative conditioning can enhance olfactory acuity for odors that are the same as or similar to the learned odorant, but not for odors dissimilar to the learned odorant. Furthermore, scopolamine injected before associative conditioning can block the acquisition of this learned enhancement in olfactory acuity. These results could have important implications for mechanisms of olfactory perception and memory, as well as for correlating behavioral olfactory acuity with observed spatial representations of odorant features in the olfactory system. PMID- 11784815 TI - Despair of repair. PMID- 11784816 TI - When can antiepileptic drugs be safely withdrawn? PMID- 11784817 TI - Thunderclap headache. AB - The aim is to review the background underlying the debate related to the alternative nomenclatures for and the most appropriate diagnostic evaluation of patients with thunderclap headache. The clinical profile and differential diagnosis of thunderclap headache is described, and a nosological framework and diagnostic approach to this group of patients is proposed. PMID- 11784819 TI - Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy. AB - OBJECTIVES: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. METHODS: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. RESULTS: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. CONCLUSIONS: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors. PMID- 11784818 TI - Neuropsychiatry of the basal ganglia. AB - This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are important links between parts of the brain that have classically been considered to be related to emotional functioning and brain regions previously considered to have largely motor functions. The basal ganglia have a role in the development and integration of psychomotor behaviours, involving motor functions, memory and attentional mechanisms, and reward processes. PMID- 11784820 TI - Heart rate dynamics in refractory and well controlled temporal lobe epilepsy. AB - OBJECTIVES: Disorders of cardiovascular and other autonomic nervous system functions are often found in patients with temporal lobe epilepsy (TLE). Cardiovascular dysregulation in TLE has previously been quantified assessing traditional time and frequency domain measures of heart rate (HR) variability from short term ECG recordings. However, new complexity and fractal measures of HR variability based on non-linear dynamics and fractals ("chaos theory") may disclose certain patterns of HR dynamics that cannot be detected using only conventional measures. METHODS: In addition to the traditional spectral and non spectral components of HR variability, fractal correlation properties, approximate entropy (ApEn) of RR interval dynamics, and the slope of the power law relation were measured from 24 hour ambulatory ECG recordings to evaluate interictal autonomic cardiovascular regulatory function in 19 patients with refractory TLE, 25 patients with well controlled TLE, and in 34 healthy age and sex matched control subjects. RESULTS: The traditional time and frequency domain measures were lower in patients with TLE than in controls (p<0.05). In addition, the power law slope (p<0.005) and ApEn (p<0.05) were also reduced in TLE patients. Furthermore, ApEn was smaller in patients with refractory TLE than in patients with well-controlled TLE ( p<0.01), whereas the long term fractal correlation value alpha2 was lower in patients with well controlled TLE (p<0.05). An altered HR variation was not associated with any particular AED regimen. CONCLUSIONS: In addition to reduced overall HR variability, the long term fractal organisation and complexity of HR dynamics seem to be altered in TLE. These abnormalities in HR behaviour may partly contribute to the occurrence of adverse cardiovascular events, such as life threatening arrhythmias in patients with TLE. PMID- 11784821 TI - Swallowing and voice effects of Lee Silverman Voice Treatment (LSVT): a pilot study. AB - OBJECTIVE: To define the effects of Lee Silverman Voice Treatment (LSVT on swallowing and voice in eight patients with idiopathic Parkinson's disease. METHODS: Each patient received a modified barium swallow (MBS) in addition to voice recording before and after 1 month of LSVT. Swallowing motility disorders were defined and temporal measures of the swallow were completed from the MBS. Voice evaluation included measures of vocal intensity, fundamental frequency, and the patient's perception of speech change. RESULTS: before LSVT, the most prevalent swallowing motility disorders were oral phase problems including reduced tongue control and strength. Reduced tongue base retraction resulting in residue in the vallecula was the most common disorder in the pharyngeal stage of the swallow. Oral transit time (OTT) and pharyngeal transit time (PTT) were prolonged. After LSVT, there was an overall 51% reduction in the number of swallowing motility disorders. Some temporal measures of swallowing were also significantly reduced as was the approximate amount of oral residue after 3 ml and 5 ml liquid swallows. Voice changes after LSVT included a significant increase in vocal intensity during sustained vowel phonation as well as during reading. CONCLUSIONS: LSVT seemingly improved neuromuscular control of the entire upper aerodigestive tract, improving oral tongue and tongue base function during the oral and pharyngeal phases of swallowing as well as improving vocal intensity. PMID- 11784822 TI - Distribution patterns of demyelination correlate with clinical profiles in chronic inflammatory demyelinating polyneuropathy. AB - BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. OBJECTIVE: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. METHODS: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-alpha was measured by immunoassay. RESULTS: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF alpha concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. CONCLUSIONS: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP. PMID- 11784823 TI - Footdrop after peroneal nerve lesion. PMID- 11784824 TI - The prevalence of "pure" autosomal dominant hereditary spastic paraparesis in the island of Ireland. AB - OBJECTIVES: Hereditary spastic paraparesis (HSP) is clinically and genetically heterogeneous. "Pure" autosomal dominant (AD) HSP is most common and eight genetic loci are identified to date. Previous studies have included autosomal recessive and sporadic cases in prevalence calculations. This study aimed to determine the prevalence and features of pure ADHSP in the island of Ireland. METHODS: Index cases were identified from a 5 year survey of all adult and paediatric neurologists, clinical geneticists, hospital records, and hospital inpatient enquiry system data in Ireland, north and south. Families were examined by two neurologists and classified as affected or unaffected according to specific criteria. The prevalence date was set at 1 June 2000 and the midyear population estimate for the previous year was 5.436 million. RESULTS: Eighty two patients with pure ADHSP and a further 12 obligate carriers from 19 families were identified. In total 69 patients with pure ADHSP were alive and resident in Ireland at the prevalence date. Twenty nine per cent of these were asymptomatic but with signs of paraparesis. CONCLUSIONS: The prevalence of ADHSP in Ireland to estimated to be 1.27/100 000 population. The high proportion of asymptomatic cases and obligate carriers means that this condition is likely to be underdiagnosed. PMID- 11784825 TI - Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor. AB - OBJECTIVES: To evaluate the impact of thalamic deep brain stimulation (DBS) on disability and health-related quality of life in patients with essential tremor. METHODS: Twenty seven consecutive patients were evaluated prospectively, before surgery and at a mean of 12 months (range 6-26) after thalamic DBS. Assessment tools included the Fahn-Tolosa-Marin tremor rating scale (TRS), activities of daily living (ADL) taxonomy, Nottingham health profile (NHP) and the visual analogue scale (VAS) for measuring impact of disease on life. Additional information on the side effects of, and expectations from surgery was obtained by interview. RESULTS: Thalamic DBS improved the ability of the patients in eating, drinking, writing, home maintenance, hobbies, and participation in society. Activities of daily life requiring bimanual skills were less improved. The emotional condition of the patients was positively affected and the negative impact of the disease on life as a whole, and on social life was decreased. Seventy per cent of the patients considered that the surgical treatment met their expectations. CONCLUSIONS: After thalamic DBS, health-related quality of life including disability in ADL and social life were improved in patients with essential tremor. PMID- 11784826 TI - Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation. AB - OBJECTIVES: Bilateral chronic high frequency stimulation of the subthalamic nucleus (STN), through the stereotactical placement of stimulating electrodes, effectively improves the motor symptoms of severe Parkinson's disease. Intraoperative neurophysiological and clinical monitoring techniques (neuronal electrical activity recording and intraoperative stimulation) may improve and refine the localisation of the nucleus. The objective of this work was to compare the preoperative CT and MRI localisation with the intraoperative neurophysiological identification of STN. The relation between the localisation of the STN and the position of the most effective contact of the permanent quadripolar electrode at a 3 month and 1 year follow up was also studied. METHODS: Fourteen consecutive parkinsonian patients were submitted to bilateral implant for STN stimulation. All the patients underwent a standard MRI and stereotactic CT to obtain, by image fusion and localisation software, the stereotactical coordinates of STN. The STN extension and boundaries were identified by a semimicrorecording of the neuronal electrical activity. The definitive quadripolar electrode was positioned to locate at least two contacts within the STN recording area. Intraoperative macrostimulation was performed to confirm the correct position of the electrode. Postoperative clinical evaluation of the effects of stimulation was checked for each contact of the quadripolar electrode testing the improvement on contralateral rigidity to select the best contact. This evaluation was repeated at 3 months and 1 year after surgery. RESULTS: In 35.7% of the procedures it was necessary to perform more than one track to get a recording of neuronal activity consistent with STN. The mean position of the central point of all the 28 STN recording areas in respect of the AC-PC line midpoint was 2.7 mm posterior (SD 0.7), 3.8 mm inferior (SD 1.1), and 11.6 mm lateral (SD 0.9), and the mean distance between the anatomical target and the central point of the STN as defined by intraoperative recording was 0.5 mm (SD 0.5) on the anteroposterior plane, 0.7 mm (SD 0.7) on the lateral plane, and 0.9 mm (SD 0.6) on the vertical plane. At 1 year the mean position of the central point of the most effective contact of the electrode in respect of the AC-PC line midpoint was 1.7 mm posterior (SD 0.9), 1.7 mm inferior (SD 1.5), and 12.3 mm lateral (SD 0.9). CONCLUSION: The results highlight the role of the intraoperative recording to get a more accurate localisation of the STN in surgery for Parkinson's disease, allowing the identification of the boundaries and of the extension of the nucleus. The most effective contact of the quadripolar electrode was always in the upper part of the STN recording area or immediately above it, suggesting a role of this region in the clinical effectiveness of the STN electrical stimulation. PMID- 11784827 TI - The natural history and treatment of acquired hemidystonia: report of 33 cases and review of the literature. AB - OBJECTIVE: To evaluate the natural history and response to treatment in hemidystonia. METHODS: 190 Cases of hemidystonia were identified; 33 patients in this series and 157 from the world literature. Data was collected on aetiology, age of onset, latency, lesion location, and response to treatment. RESULTS: The most common aetiologies of hemidystonia were stroke, trauma, and perinatal injury. Mean age of onset was 20 years in this series and 25.7 years in the literature. The average latency from insult to dystonia was 4.1 years in this series and 2.8 years in the literature, with the longest latencies occurring after perinatal injury. Basal ganglia lesions were identified in 48% of cases in this series and 60% of the cases in the literature, most commonly involving the putamen. Patients experienced benefit from medical therapy in only 26% of medication trials in this series and in only 35% of trials in the literature. In the patients reported here, the benzodiazepines clonazepam and diazepam were the most effective medications with 50% of trials resulting in at least some benefit. In the literature, anticholinergic drugs were most effective with 41% of trials resulting in benefit. Surgery was successful in five of six cases in this series and in 22 of 23 cases in the literature. However, in 12 cases, results were transient. CONCLUSIONS: The most common cause of hemidystonia is stroke, with the lesion most commonly involving the basal ganglia. Hemidystonia responds poorly to most medical therapies, but some patients may benefit from treatment with benzodiazepines or anticholinergic drugs. Surgical therapy may be successful but benefit is often transient. PMID- 11784828 TI - Triangular backgrounds shift the bias of line bisection performance in hemispatial neglect. AB - OBJECTIVE: Patients with left neglect on line bisection show normal implicit sensitivity to manipulations of both the stimulus and the visual background. Three experiments were designed to define this sensitivity more exactly. METHODS: Normal controls and patients with left neglect performed a series of horizontal line bisection tasks. Independent variables were the configurations of the backgrounds for the line-rectangle, square, circle, left and right pointing isosceles triangles-and whether the background was the shape of the piece of paper or an outline drawn on a standard piece of paper. In a separate experiment different components of the triangle were outlined on a piece of paper. Deviation from true midpoint was calculated. RESULTS: Simply placing the target lines in a symmetric background such as a square or circle did not reliably reduce neglect. A triangle asymmetric in the horizontal plane caused a shift in bisection away from the triangle's vertex. With right pointing triangles the perceived midpoint shifted to the left of true centre (crossed over). The effects of the triangles were comparable in the patients and the controls when controlled for baseline bisection bias. The critical components of the triangles were the angular legs. This effect of background was not influenced by lesion site or by hemianopia. CONCLUSIONS: Patients with left visual neglect remain sensitive to covert manipulations of the visual background that implicitly shift the perceived midpoint of a horizontal line. This effect is strong enough to eliminate neglect on a bisection task. The mechanism of this effect is expressed through preattentive visual capacities. PMID- 11784829 TI - Effects of left parietal injury on covert orienting of attention. AB - OBJECTIVE: To assess the effects of left parietal injury on covert visual attention during a detection task and a pointing task. METHODS: The Posner's paradigm was given to a patient who was found at the age of 74 to have spent all his life without the left parietal lobe as a result of a congenital perinatal insult and to a control subject. In one session subjects were required to provide an arbitrary response at stimulus appearance (key press). In another session subjects were required to point to the stimulus. RESULTS: The patient was able to disengage covert attention from a cued position when the task was to provide an arbitrary key press response in a similar fashion to a control subject with no neurological deficits. By contrast, he was impaired in disengaging attention from a cued position when the task was to reprogramme an overt pointing action. CONCLUSIONS: Response to cued information is differentially available depending on task. It is suggested that mechanisms concerned with the attention for action systems are located within the left parietal lobe. PMID- 11784830 TI - Gait apraxia after bilateral supplementary motor area lesion. AB - OBJECTIVES: The study aimed at addressing the issue of the precise nature of gait apraxia and the cerebral dysfunction responsible for it. METHODS: The case of a patient, affected by a bilateral infarction limited to a portion of the anterior cerebral artery territory is reported. The patient's ability to walk was formally assessed by means of a new standardised test. RESULTS: Due to an anomaly within the anterior cerebral artery system, the patient's lesion was centred on the supplementary motor regions of both hemispheres. He presented with clear signs of gait apraxia that could not be accounted for by paresis or other neurological deficits. No signs of any other form of apraxia were detected. CONCLUSIONS: The clinical profile of the patient and the analysis of 49 cases from previous literature suggest that gait apraxia should be considered a clinical entity in its own right and lesions to the supplementary motor areas are responsible for it. PMID- 11784831 TI - Physical and psychological correlates of primary headache in young adulthood: a 26 year longitudinal study. AB - OBJECTIVES: To determine if physical and/or psychological risk factors could differentiate between subtypes of primary headache (migraine, tension-type headache (TTH), and coexisting migraine and TTH (combined)) among members of a longitudinal birth cohort study. METHODS: At age 26, the headache status of members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) was determined using International Headache Society criteria. Headache history and potential physical and psychological correlates of headache were assessed. These factors included perinatal problems and injuries sustained to age 26; and behavioural, personality, and psychiatric disorders assessed between ages 5 to 21. RESULTS: The 1 year prevalences for migraine, TTH, and combined headache at the age of 26 were 7.2%, 11.1%, and 4.3%, respectively. Migraine was related to maternal headache, anxiety symptoms in childhood, anxiety disorders during adolescence and young adulthood, and the stress reactivity personality trait at the age of 18. TTH was significantly associated with neck or back injury in childhood (before the age of 13). Combined headache was related to maternal headache and anxiety disorder at 18 and 21 only among women with a childhood history of headache. Headache status at the age of 26 was unrelated to a history of perinatal complication, neurological disorder, or mild traumatic head injury. CONCLUSIONS: Migraine and TTH seem to be distinct disorders with different developmental characteristics. Combined headache may also have a distinct aetiology. PMID- 11784832 TI - Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis. AB - OBJECTIVES: Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis. METHOD: The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire. RESULTS: The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence. CONCLUSIONS: The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis. PMID- 11784834 TI - Julius Wagner-Jauregg (1857-1940). PMID- 11784833 TI - Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids. AB - OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans. PMID- 11784836 TI - Anticholinergic drugs: response of parkinsonism not responsive to levodopa. AB - A 41 year old man with parkinsonism and pyramidal signs is described. He was non responsive to levodopa and dopamine receptor agonists but dramatically responded to trihexyphenidyl. In this patient, brain MRI showed bilateral hyperintensities along the corticospinal tracts on T2 weighted images. PET studies showed a decrease in (18)F-6-fluorodopa uptake in the putamen contralateral to the more affected limbs and normal D(2) receptor binding in the putamen. The PET and MRI findings and responsiveness to antiparkinsonian agents suggested degeneration of nigrostriatal dopaminergic neurons, striatal output pathways, and corticospinal tracts. PMID- 11784835 TI - Immediate and delayed effects of risperidone on cerebral metabolism in neuroleptic naive schizophrenic patients: correlations with symptom change. AB - OBJECTIVE: Different symptom patterns have been shown to be associated with specific patterns of cerebral metabolic activity in schizophrenia. Treatment with various neuroleptic drugs results in decreased metabolism in frontal cortical regions. The temporal and regional relation between changes in metabolism and symptom improvement after treatment with risperidone was studied in eight previously unmedicated schizophrenic patients. METHOD: Cerebral metabolic activity was measured using PET before neuroleptic exposure, after the first dose of risperidone, and after 6 weeks of treatment. Pearson correlations were calculated for regions of significant change in metabolism and symptom change. RESULTS: After 6 weeks of treatment significant deactivations were seen in the left lateral cortical frontal region and medial frontal cortex. Significant changes were detectable in the medial frontal region 90 minutes after the first dose of risperidone. Patients with higher baseline activity in the identified medial frontal cluster had higher baseline positive symptom scores and reduction in medial frontal metabolism was correlated with reduction in positive symptom score. CONCLUSION: The evidence suggests that the reduction in medial-frontal activity after treatment with risperidone is a direct effect of risperidone and not a consequence of symptom improvement. Reduction of medial frontal metabolism may be one of the physiological mechanisms by which risperidone alleviates symptoms of psychosis in schizophrenia. PMID- 11784837 TI - Antiepileptic drugs: coprescription of proconvulsant drugs and oral contraceptives: a national study of antiepileptic drug prescribing practice. AB - OBJECTIVES: To determine the frequency of coprescription of antiepileptic drugs (AEDs) and drugs with proconvulsant potential and of coprescription of AEDs and low dose oral contraceptives. METHODS: Using information from all 294 fully computerised general practices participating in the General Practice Research Database who entered complete data in 1995, persons were identified who had a prescription for an antiepileptic drug and who had a diagnosis of epilepsy or epileptic seizures in their medical records. Other medication was also recorded. RESULTS: Of women with epilepsy aged 15-45, 16.7% were on the oral contraceptive pill and of 200 on both an enzyme inducing AED and an oral contraceptive, 56% were on formulations with an estrogen content less than 50 microg. This will be associated with increased risk of contraceptive failure and unwanted pregnancy. Over 10% of all AED prescriptions in adults were associated with simultaneous prescription of at least one drug with a potential proconvulsant effect. CONCLUSIONS: Prescribers should be alert to the possibility of pharmacodynamic and pharmacokinetic interactions between AEDs and other medication. With the aging of the population of people with seizures, and the polypharmacy often associated with old age, the likelihood of adversely interacting drug combinations will increase. PMID- 11784838 TI - Fear conditioned changes of heart rate in patients with medial cerebellar lesions. AB - Fear conditioned changes of heart rate and skin conductance responses were investigated in patients with medial cerebellar lesions. A classical conditioning paradigm with a tone as the conditioned stimulus (CS) and an electrical shock as the unconditioned stimulus (US) was tested on five patients with medial cerebellar lesions due to surgery for astrocytoma and five controls. The CS preceded the US by 5900 ms and coterminated with the US. Changes in heart rate and skin conductance responses were obtained as measures for autonomic fear responses. Effects of conditioning were quantified by comparison of the habituation and extinction phases. Controls, but not cerebellar patients, showed a significant decrease of heart rate during fear conditioning. However, there were no significant fear conditioned changes in electrodermal responses in either group. In summary, the medial cerebellum seems to be involved in fear-conditioned bradycardia in humans. PMID- 11784839 TI - Evaluation of the management of optic neuritis: audit on the neurological and ophthalmological practice in the north west of England. AB - The management of acute optic neuritis by neurologists and ophthalmologists in the north west of England was assessed in the light of the Optic Neuritis Treatment Trial (ONTT) recommendations. A questionnaire on a fictitious case of typical unilateral optic neuritis was mailed to all consultant ophthalmologists and neurologists working in the North West and Merseyside Health Authorities. They were then asked to comment on management of the case. Fifty two out of 86 ophthalmologists and 20 out of 28 neurologists replied. The overall response rate was 63%. Sixty five per cent of neurologists and 46% of ophthalmologists would investigate a typical case of acute optic neuritis further. Forty six per cent of neurologists and 36% of ophthalmologists were likely to arrange MRI of the brain or orbit. Significantly more neurologists (55%) than ophthalmologists (9%) chose to treat with intravenous methylprednisolone (p<0.005). Significantly more ophthalmologists (64%) than neurologists (32%) chose not to give steroids (p<0.025). Oral prednisolone alone was rarely selected for treatment. Respondents were more likely to discuss multiple sclerosis with the referring doctor than with the patient. Only 32% of ophthalmologists and 20% of neurologists would clearly mention the possibility of improvement to the patient. Clear differences in practice between ophthalmologists and neurologists remain. A consensus on practice guidelines on the issues raised might be useful. PMID- 11784840 TI - Mexiletine is effective on segmental hyperhidrosis: report of two cases. PMID- 11784841 TI - Does the presence of a pontine trigeminal lesion represent an absolute contraindication for microvascular decompression in drug resistant trigeminal neuralgia? PMID- 11784842 TI - Reversal of tissue hypoxia by a single intraventricular dose of sodium nitroprusside in a patient with severe medically refractory cerebral vasospasm after subarachnoid haemorrhage. PMID- 11784843 TI - Transcranial magnetic stimulation alleviates truncal ataxia in spinocerebellar degeneration. PMID- 11784844 TI - Agraphia in Kanji after a contusional haemorrhage in the left temporo-occipital lobe. PMID- 11784845 TI - Successful autologous stem cell transplantation in a patient with chronic inflammatory demyelinating polyneuropathy. PMID- 11784846 TI - Unusual presentation of a primary spinal lymphoma. PMID- 11784847 TI - Orientation agnosia in pentagon copying. PMID- 11784848 TI - Histone-dependent association of Tup1-Ssn6 with repressed genes in vivo. AB - The Tup1-Ssn6 complex regulates diverse classes of genes in Saccharomyces cerevisiae and serves as a model for corepressor functions in many organisms. Tup1-Ssn6 does not directly bind DNA but is brought to target genes through interactions with sequence-specific DNA binding factors. Full repression by Tup1 Ssn6 appears to require interactions with both the histone tails and components of the general transcription machinery, although the relative contribution of these two pathways is not clear. Here, we map Tup1 locations on two classes of Tup1-Ssn6-regulated genes in vivo via chromatin immunoprecipitations. Distinct profiles of Tup1 are observed on a cell-specific genes and DNA damage-inducible genes, suggesting that alternate repressive architectures may be created on different classes of repressed genes. In both cases, decreases in acetylation of histone H3 colocalize with Tup1. Strikingly, although loss of the Srb10 mediator protein had no effect on Tup1 localization, both histone tail mutations and histone deacetylase mutations crippled the association of Tup1 with target loci. Together with previous findings that Tup1-Ssn6 physically associates with histone deacetylase activities, these results indicate that the repressor complex alters histone modification states to facilitate interactions with histones and that these interactions are required to maintain a stable repressive state. PMID- 11784849 TI - Murine de novo methyltransferase Dnmt3a demonstrates strand asymmetry and site preference in the methylation of DNA in vitro. AB - CpG methylation is involved in a wide range of biological processes in vertebrates as well as in plants and fungi. To date, three enzymes, Dnmt1, Dnmt3a, and Dnmt3b, are known to have DNA methyltransferase activity in mouse and human. It has been proposed that de novo methylation observed in early embryos is predominantly carried out by the Dnmt3a and Dnmt3b methyltransferases, while Dntm1 is believed to be responsible for maintaining the established methylation patterns upon replication. Analysis of the sites methylated in vivo using the bisulfite genomic sequencing method confirms the previous finding that some regions of the plasmid are much more methylated by Dnmt3a than other regions on the same plasmid. However, the preferred targets of the enzyme cannot be determined due to the presence of other methylases, DNA binding proteins, and chromatin structure. To discern the DNA targets of Dnmt3a without these compounding factors, sites methylated by Dnmt3a in vitro were analyzed. These analyses revealed that the two cDNA strands have distinctly different methylation patterns. Dnmt3a prefers CpG sites on a strand in which it is flanked by pyrimidines over CpG sites flanked by purines in vitro. These findings indicate that, unlike Dnmt1, Dnmt3a most likely methylates one strand of DNA without concurrent methylation of the CpG site on the complementary strand. These findings also indicate that Dnmt3a may methylate some CpG sites more frequently than others, depending on the sequence context. Methylation of each DNA strand independently and with possible sequence preference is a novel feature among the known DNA methyltransferases. PMID- 11784850 TI - Tumor necrosis factor-related apoptosis-inducing ligand induces caspase-dependent interleukin-8 expression and apoptosis in human astroglioma cells. AB - Among the tumor necrosis factor (TNF) family of cytokines, FasL and TNF-related apoptosis-inducing ligand (TRAIL) are known to induce cell death via caspase activation. Recently, other biological functions of these death ligands have been postulated in vitro and in vivo. It was previously shown that Fas ligation induces chemokine expression in human glioma cells. In this study, we investigated whether the TRAIL-DR5 system transduces signals similar to those induced by other TNF family ligands and receptors. To address this issue, two human glioma cell lines, CRT-MG and U87-MG, were used, and an agonistic antibody against DR5 (TRA-8) and human recombinant TRAIL were used to ligate DR5. We demonstrate that DR5 ligation by either TRAIL or TRA-8 induces two functional outcomes, apoptosis and expression of the chemokine interleukin-8 (IL-8); the nonspecific caspase inhibitor Boc-D-Fmk blocks both TRAIL-mediated cell death and IL-8 production; the caspase 3-specific inhibitor z-DEVD-Fmk suppresses TRAIL mediated apoptosis but not IL-8 induction; caspase 1- and 8-specific inhibitors block both TRAIL-mediated cell death and IL-8 production; and DR5 ligation by TRAIL mediates AP-1 and NF-kappaB activation, which can be inhibited by caspase 1 and 8-specific inhibitors. These findings collectively indicate that DR5 ligation on human glioma cells leads to apoptosis and that the activation of AP-1 and NF-kappaB leads to the induction of IL-8 expression; these responses are dependent on caspase activation. Therefore, the TRAIL-DR5 system has a role not only as an inducer of apoptotic cell death but also as a transducer for proinflammatory and angiogenic signals in human brain tumors. PMID- 11784851 TI - Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. AB - Mitogen-activated protein kinase (MAPK) pathways coordinate critical cellular responses to mitogens, stresses, and developmental cues. The coupling of MAPK kinase kinase (MAP3K) --> MAPK kinase (MEK) --> MAPK core pathways to cell surface receptors remains poorly understood. Recombinant forms of MAP3K MEK kinase 1 (MEKK1) interact in vivo and in vitro with the STE20 protein homologue germinal center kinase (GCK), and both GCK and MEKK1 associate in vivo with the adapter protein tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2). These interactions may couple TNF receptors to the SAPK/JNK family of MAPKs; however, a molecular mechanism by which these proteins might collaborate to recruit the SAPKs/JNKs has remained elusive. Here we show that endogenous GCK and MEKK1 associate in vivo. In addition, we have developed an in vitro assay system with which we demonstrate that purified, active GCK and TRAF2 activate MEKK1. The RING domain of TRAF2 is necessary for optimal in vitro activation of MEKK1, but the kinase domain of GCK is not. Autophosphorylation within the MEKK1 kinase domain activation loop is required for activation. Forced oligomerization also activates MEKK1, and GCK elicits enhanced oligomerization of coexpressed MEKK1 in vivo. These results represent the first activation of MEKK1 in vitro using purified proteins and suggest a mechanism for MEKK1 activation involving induced oligomerization and consequent autophosphorylation mediated by upstream proteins. PMID- 11784853 TI - Translocation after synthesis of a four-nucleotide RNA commits RNA polymerase II to promoter escape. AB - Transcription is a complex process, the regulation of which is crucial for cellular and organismic growth and development. Deciphering the molecular mechanisms that define transcription is essential to understanding the regulation of RNA synthesis. Here we describe the molecular mechanism of escape commitment, a critical step in early RNA polymerase II transcription. During escape commitment ternary transcribing complexes become stable and committed to proceeding forward through promoter escape and the remainder of the transcription reaction. We found that the point in the transcription reaction at which escape commitment occurs depends on the length of the transcript RNA (4 nucleotides [nt]) as opposed to the position of the active site of the polymerase with respect to promoter DNA elements. We found that single-stranded nucleic acids can inhibit escape commitment, and we identified oligonucleotides that are potent inhibitors of this specific step. These inhibitors bind RNA polymerase II with low nanomolar affinity and sequence specificity, and they block both promoter dependent and promoter-independent transcription, the latter occurring in the absence of general transcription factors. We demonstrate that escape commitment involves translocation of the RNA polymerase II active site between synthesis of the third and fourth phosphodiester bonds. We propose that a conformational change in ternary transcription complexes occurs during translocation after synthesis of a 4-nt RNA to render complexes escape committed. PMID- 11784852 TI - A novel RNA polymerase I transcription initiation factor, TIF-IE, commits rRNA genes by interaction with TIF-IB, not by DNA binding. AB - In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE. PMID- 11784855 TI - Stimulation of DNA synthesis activity of human DNA polymerase kappa by PCNA. AB - Humans have three DNA polymerases, Poleta, Polkappa, and Poliota, which are able to promote replication through DNA lesions. However, the mechanism by which these DNA polymerases are targeted to the replication machinery stalled at a lesion site has remained unknown. Here, we provide evidence for the physical interaction of human Polkappa (hPolkappa) with proliferating cell nuclear antigen (PCNA) and show that PCNA, replication factor C (RFC), and replication protein A (RPA) act cooperatively to stimulate the DNA synthesis activity of hPolkappa. The processivity of hPolkappa, however, is not significantly increased in the presence of these protein factors. The efficiency (V(max)/K(m)) of correct nucleotide incorporation by hPolkappa is enhanced approximately 50- to 200-fold in the presence of PCNA, RFC, and RPA, and this increase in efficiency is achieved by a reduction in the apparent K(m) for the nucleotide. Although in the presence of these protein factors, the efficiency of the insertion of an A nucleotide opposite an abasic site is increased approximately 40-fold, this reaction still remains quite inefficient; thus, it is unlikely that hPolkappa would bypass an abasic site by inserting a nucleotide opposite the site. PMID- 11784854 TI - Stromal cell-derived factor 1alpha activates LIM kinase 1 and induces cofilin phosphorylation for T-cell chemotaxis. AB - Stromal cell-derived factor 1 alpha (SDF-1alpha), the ligand for G-protein coupled receptor CXCR4, is a chemotactic factor for T lymphocytes. LIM kinase 1 (LIMK1) phosphorylates cofilin, an actin-depolymerizing and -severing protein, at Ser-3 and regulates actin reorganization. We investigated the role of cofilin phosphorylation by LIMK1 in SDF-1alpha-induced chemotaxis of T lymphocytes. SDF 1alpha significantly induced the activation of LIMK1 in Jurkat human leukemic T cells and peripheral blood lymphocytes. SDF-1alpha also induced cofilin phosphorylation, actin reorganization, and activation of small GTPases, Rho, Rac, and Cdc42, in Jurkat cells. Pretreatment with pertussis toxin inhibited SDF 1alpha-induced LIMK1 activation, thus indicating that Gi protein is involved in LIMK1 activation. Expression of dominant negative Rac (DN-Rac), but not DN-Rho or DN-Cdc42, blocked SDF-1alpha-induced activation of LIMK1, which means that SDF 1alpha-induced LIMK1 activation is mediated by Rac but not by Rho or Cdc42. We used a cell-permeable peptide (S3 peptide) that contains the phosphorylation site (Ser-3) of cofilin to inhibit the cellular function of LIMK1. S3 peptide inhibited the kinase activity of LIMK1 in vitro. Treatment of Jurkat cells with S3 peptide inhibited the SDF-1alpha-induced cofilin phosphorylation, actin reorganization, and chemotactic response of Jurkat cells. These results suggest that the phosphorylation of cofilin by LIMK1 plays a critical role in the SDF 1alpha-induced chemotactic response of T lymphocytes. PMID- 11784856 TI - The neuronal basic helix-loop-helix transcription factor NSCL-1 is dispensable for normal neuronal development. AB - The neuronal stem cell leukemia (NSCL) basic helix-loop-helix factors are neural cell-specific transcription factors. We have disrupted the NSCL-1 gene by homologous recombination and replaced the coding region with a beta-galactosidase reporter cassette to study the role of NSCL-1 in neuronal development and to follow the fate of NSCL-1 mutant cells. NSCL-1 mutant mice are viable and fertile on various genetic backgrounds and do not show any obvious signs of neurological malfunction. No differences in the distribution of NSCL-1 mutant or heterozygous neuronal cells were observed in the diencephalon, hippocampus, neocortex, and cerebellum at different stages of development. Likewise, no defects were found in the laminar organization of the cortex, and the distinct neuronal subpopulation appeared normal during development of the neocortex. Analysis of sensory neurons which strongly express NSCL-1 revealed that the spatiotemporal expression of neuronal differentiation factors, such as NeuroD and SCG-10, was not altered in developing distal and proximal cranial ganglia of mutant mice. In the cerebellum expression of NSCL-1 was confined to the proliferative and premigratory zone of the external granular layer and the internal granular layer. Interestingly, unlike cerebella of Math1(-/-) or NeuroD2(-/-) mice, NSCL-1-deficient mice have no obvious developmental defect, and neurons of the cerebellum appeared fully differentiated. Despite similar expression patterns of NSCL-1 and NSCL-2 in various areas of the diencephalon, including the arcuate nucleus and paraventricular nucleus, NSCL-1(-/-) mice are fertile and show no adult onset of obesity like NSCL-2 mutant mice. Double-mutant NSCL-1(-/-)-NSCL-2(-/-) mice do not show any additional obvious malformations of the central nervous system, although both genes are expressed in a largely overlapping pattern. Our results argue against a simple functional redundancy within the NSCL gene family. PMID- 11784857 TI - Removal of a single alpha-tubulin gene intron suppresses cell cycle arrest phenotypes of splicing factor mutations in Saccharomyces cerevisiae. AB - Genetic and biochemical studies of Schizosaccharomyces pombe and Saccharomyces cerevisiae have identified gene products that play essential functions in both pre-mRNA splicing and cell cycle control. Among these are the conserved, Myb related CDC5 (also known as Cef1p in S. cerevisiae) proteins. The mechanism by which loss of CDC5/Cef1p function causes both splicing and cell cycle defects has been unclear. Here we provide evidence that cell cycle arrest in a new temperature-sensitive CEF1 mutant, cef1-13, is an indirect consequence of defects in pre-mRNA splicing. Although cef1-13 cells harbor global defects in pre-mRNA splicing discovered through intron microarray analysis, inefficient splicing of the alpha-tubulin-encoding TUB1 mRNA was considered as a potential cause of the cef1-13 cell cycle arrest because cef1-13 cells arrest uniformly at G(2)/M with many hallmarks of a defective microtubule cytoskeleton. Consistent with this possibility, cef1-13 cells possess reduced levels of total TUB1 mRNA and alpha tubulin protein. Removing the intron from TUB1 in cef1-13 cells boosts TUB1 mRNA and alpha-tubulin expression to near wild-type levels and restores microtubule stability in the cef1-13 mutant. As a result, cef1-13 tub1Deltai cells progress through mitosis and their cell cycle arrest phenotype is alleviated. Removing the TUB1 intron from two other splicing mutants that arrest at G(2)/M, prp17Delta and prp22-1 strains, permits nuclear division, but suppression of the cell cycle block is less efficient. Our data raise the possibility that although cell cycle arrest phenotypes in prp mutants can be explained by defects in pre-mRNA splicing, the transcript(s) whose inefficient splicing contributes to cell cycle arrest is likely to be prp mutant dependent. PMID- 11784858 TI - Hsp27 as a negative regulator of cytochrome C release. AB - We previously showed that Hsp27 protects against apoptosis through its interaction with cytosolic cytochrome c. We have revisited this protective activity in murine cell lines expressing different levels of Hsp27. We report that Hsp27 also interferes, in a manner dependent on level of expression, with the release of cytochrome c from mitochondria. Moreover, a decreased level of endogenous Hsp27, which sensitized HeLa cells to apoptosis, reduced the delay required for cytochrome c release and procaspase 3 activation. The molecular mechanism regulating this function of Hsp27 is unknown. In our cell systems, Hsp27 is mainly cytosolic and only a small fraction of this protein colocalized with mitochondria. Moreover, we show that only a very small fraction of cytochrome c interacts with Hsp27, hence excluding a role of this interaction in the retention of cytochrome c in mitochondria. We also report that Bid intracellular relocalization was altered by changes in Hsp27 level of expression, suggesting that Hsp27 interferes with apoptotic signals upstream of mitochondria. We therefore investigated if the ability of Hsp27 to act as an expression dependent modulator of F-actin microfilaments integrity was linked to the retention of cytochrome c in mitochondria. We show here that the F-actin depolymerizing agent cytochalasin D rapidly induced the release of cytochrome c from mitochondria and caspase activation. This phenomenon was delayed in cells pretreated with the F-actin stabilizer phalloidin and in cells expressing a high level of Hsp27. This suggests the existence of an apoptotic signaling pathway linking cytoskeleton damages to mitochondria. This pathway, which induces Bid intracellular redistribution, is negatively regulated by the ability of Hsp27 to protect F-actin network integrity. However, this upstream pathway is probably not the only one to be regulated by Hsp27 since, in staurosporine-treated cells, phalloidin only partially inhibited cytochrome c release and caspase activation. Moreover, in etoposide-treated cells, Hsp27 still delayed the release of cytochrome c from mitochondria and Bid intracellular redistribution in conditions where F-actin was not altered. PMID- 11784860 TI - Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient mice. AB - We have constructed an ALDH3a1 null mouse to investigate the role of this enzyme that comprises nearly one-half of the total water-soluble protein in the mouse corneal epithelium. ALDH3a1-deficient mice are viable and fertile, have a corneal epithelium with a water-soluble protein content approximately half that of wild type mice, and contain no ALDH3a1 as determined by zymograms and immunoblots. Despite the loss of protein content and ALDH3a1 activity, the ALDH3a1(-/-) mouse corneas appear indistinguishable from wild-type corneas when examined by histological analysis and electron microscopy and are transparent as determined by light and slit lamp microscopy. There is no evidence for a compensating protein or enzyme. Even though the function of ALDH3a1 in the mouse cornea remains unknown, our data indicate that its enzymatic activity is unnecessary for corneal clarity and maintenance, at least under laboratory conditions. PMID- 11784859 TI - Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1). AB - Sin3 is an evolutionarily conserved corepressor that exists in different complexes with the histone deacetylases HDAC1 and HDAC2. Sin3-HDAC complexes are believed to deacetylate nucleosomes in the vicinity of Sin3-regulated promoters, resulting in a repressed chromatin structure. We have previously found that a human Sin3-HDAC complex includes HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, and two novel polypeptides SAP30 and SAP18. SAP30 is a specific component of Sin3 complexes since it is absent in other HDAC1/2 containing complexes such as NuRD. SAP30 mediates interactions with different polypeptides providing specificity to Sin3 complexes. We have identified p33ING1b, a negative growth regulator involved in the p53 pathway, as a SAP30 associated protein. Two distinct Sin3-p33ING1b-containing complexes were isolated, one of which associates with the subunits of the Brg1-based Swi/Snf chromatin remodeling complex. The N terminus of p33ING1b, which is divergent among a family of ING1 polypeptides, associates with the Sin3 complex through direct interaction with SAP30. The N-terminal domain of p33 is present in several uncharacterized human proteins. We show that overexpression of p33ING1b suppresses cell growth in a manner dependent on the intact Sin3-HDAC-interacting domain. PMID- 11784861 TI - Retinoblastoma protein transcriptional repression through histone deacetylation of a single nucleosome. AB - The retinoblastoma protein, pRb, controls transcription through recruitment of histone deacetylase to particular E2F-responsive genes. We determined the acetylation level of individual nucleosomes present in the cyclin E promoter of RB(+/+) and RB(-/-) mouse embryo fibroblasts. We also determined the effects of pRb on nucleosomal conformation by examining the thiol reactivity of histone H3 of individual nucleosomes. We found that pRb represses the cyclin E promoter through histone deacetylation of a single nucleosome, to which it and histone deacetylase 1 bind. In addition, the conformation of this nucleosome is modulated by pRb-directed histone deacetylase activity. Thus, the repressive role of pRb in cyclin E transcription and therefore cell cycle progression can be mapped to its control of the acetylation status and conformation of a single nucleosome. PMID- 11784862 TI - Molecular motor KIF1C is not essential for mouse survival and motor-dependent retrograde Golgi apparatus-to-endoplasmic reticulum transport. AB - KIF1C is a new member of the kinesin superfamily of proteins (KIFs), which act as microtubule-based molecular motors involved in intracellular transport. We cloned full-length mouse kif1C cDNA, which turned out to have a high homology to a mitochondrial motor KIF1Balpha and to be expressed ubiquitously. To investigate the in vivo significance of KIF1C, we generated kif1C(-/-) mice by knocking in the beta-galactosidase gene into the motor domain of kif1C gene. On staining of LacZ, we detected its expression in the heart, liver, hippocampus, and cerebellum. Unexpectedly, kif1C(-/-) mice were viable and showed no obvious abnormalities. Because immunocytochemistry showed partial colocalization of KIF1C with the Golgi marker protein, we compared the organelle distribution in primary lung fibroblasts from kif1C(+/+) and kif1C(-/-) mice. We found that there was no significant difference in the distribution of the Golgi apparatus or in the transport from the Golgi apparatus to the endoplasmic reticulum (ER) facilitated by brefeldin A between the two cells. This retrograde membrane transport was further confirmed to be normal by time-lapse analysis. Consequently, KIF1C is dispensable for the motor-dependent retrograde transport from the Golgi apparatus to the ER. PMID- 11784863 TI - Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. AB - Phosphorylation at a highly conserved serine residue (Ser-10) in the histone H3 tail is considered to be a crucial event for the onset of mitosis. This modification appears early in the G(2) phase within pericentromeric heterochromatin and spreads in an ordered fashion coincident with mitotic chromosome condensation. Mutation of Ser-10 is essential in Tetrahymena, since it results in abnormal chromosome segregation and extensive chromosome loss during mitosis and meiosis, establishing a strong link between signaling and chromosome dynamics. Although mitotic H3 phosphorylation has been long recognized, the transduction routes and the identity of the protein kinases involved have been elusive. Here we show that the expression of Aurora-A and Aurora-B, two kinases of the Aurora/AIK family, is tightly coordinated with H3 phosphorylation during the G(2)/M transition. During the G(2) phase, the Aurora-A kinase is coexpressed while the Aurora-B kinase colocalizes with phosphorylated histone H3. At prophase and metaphase, Aurora-A is highly localized in the centrosomic region and in the spindle poles while Aurora-B is present in the centromeric region concurrent with H3 phosphorylation, to then translocate by cytokinesis to the midbody region. Both Aurora-A and Aurora-B proteins physically interact with the H3 tail and efficiently phosphorylate Ser10 both in vitro and in vivo, even if Aurora-A appears to be a better H3 kinase than Aurora-B. Since Aurora-A and Aurora-B are known to be overexpressed in a variety of human cancers, our findings provide an attractive link between cell transformation, chromatin modifications and a specific kinase system. PMID- 11784864 TI - Gradient of E2A activity in B-cell development. AB - The E2A locus is a frequent target of chromosomal translocations in B-cell acute lymphoblastic leukemia (B-ALL). E2A encodes two products, E12 and E47, that are part of the basic helix-loop-helix (bHLH) family of transcription factors and are central in B lineage differentiation. E2A haplo-insufficiency hinders progression through three major checkpoints in B-cell development: commitment into the B lineage, at the pro-B to pre-B transition, and in the induction of immunoglobulin M (IgM) expression required for a functional BCR. These observations underscore the importance of E2A gene dosage in B-cell development. Here we show that a higher proportion of pro-B cells in E2A(+/-) mice is in the cell cycle compared to that in wild-type littermates. This increase correlates with lower p21(waf/cip1) levels, indicating that E2A has an antiproliferative function in B cell progenitors. Ectopic expression in the B lineage of SCL/Tal1, a tissue specific bHLH factor that inhibits E2A function, blocks commitment into the B lineage without affecting progression through later stages of differentiation. Furthermore, ectopic SCL expression exacerbates E2A haplo-insufficiency in B-cell differentiation, indicating that SCL genetically interacts with E2A. Taken together, these observations provide evidence for a gradient of E2A activity that increases from the pre-pro-B to the pre-B stage and suggest a model in which low levels of E2A (as in pro-B cells) are sufficient to control cell growth, while high levels (in pre-B cells) are required for cell differentiation. The antiproliferative function of E2A further suggests that in B-ALL associated with t(1;19) and t(17;19), the disruption of one E2A allele contributes to leukemogenesis, in addition to other anomalies induced by E2A fusion proteins. PMID- 11784865 TI - The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. AB - The integrin family of cell adhesion receptors are important for a diverse set of biological responses during development. Although many integrins have been shown to engage a similar set of cytoplasmic effector proteins in vitro, the importance of these proteins in the biological events mediated by different integrin receptors and ligands is uncertain. We have examined the role of one of the best characterized integrin effectors, the focal adhesion protein paxillin, by disruption of the paxillin gene in mice. Paxillin was found to be critically involved in regulating the development of mesodermally derived structures such as heart and somites. The phenotype of the paxillin(-/-) mice closely resembles that of fibronectin(-/-) mice, suggesting that paxillin is a critical transducer of signals from fibronectin receptors during early development. Paxillin was also found to play a critical role in fibronectin receptor biology ex vivo since cultured paxillin-null fibroblasts display abnormal focal adhesions, reduced cell migration, inefficient localization of focal adhesion kinase (FAK), and reduced fibronectin-induced phosphorylation of FAK, Cas, and mitogen-activated protein kinase. In addition, we found that paxillin-null fibroblasts show some defects in the cortical cytoskeleton and cell spreading on fibronectin, raising the possibility that paxillin could play a role in structures distinct from focal adhesions. Thus, paxillin and fibronectin regulate some common embryonic developmental events, possibly due to paxillin modulation of fibronectin regulated focal adhesion dynamics and organization of the membrane cytoskeletal structures that regulate cell migration and spreading. PMID- 11784867 TI - The Sur7p family defines novel cortical domains in Saccharomyces cerevisiae, affects sphingolipid metabolism, and is involved in sporulation. AB - We have discovered a novel cortical patch structure in Saccharomyces cerevisiae defined by a family of integral plasma membrane proteins, including Sur7p, Ynl194p, and Ydl222p. Sur7p-family patches localized as cortical patches that were immobile and stable. These patches were polarized to regions of the cell with a mature cell wall; they were absent from small buds and the tips of many medium-sized buds. These patches were distinct from other known cortical structures. Digestion of the cell wall caused Sur7p patches to disassemble, indicating that Sur7p requires cell wall-dependent extracellular interactions for its localization as patches. sur7Delta, ydl222Delta, and ynl194Delta mutants had reduced sporulation efficiencies. SUR7 was originally described as a multicopy suppressor of rvs167, whose product is an actin patch component. This suppression is probably mediated by sphingolipids, since deletion of SUR7, YDL222, and YNL194 altered the sphingolipid content of the yeast plasma membrane, and other SUR genes suppress rvs167 via effects on sphingolipid synthesis. In particular, the sphingoid base length and number of hydroxyl groups in inositol phosphorylceramides were altered in sur7Delta, ydl222Delta, and yne194Delta strains. PMID- 11784866 TI - The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins. AB - Activation of RAS proteins can lead to multiple outcomes by virtue of regulated signal traffic through alternate effector pathways. We demonstrate that the RAS effector protein RIN1 binds to activated RAS with an affinity (K(d), 22 nM) similar to that observed for RAF1. At concentrations close to their equilibrium dissociation constant values, RIN1 and RAF1 compete directly for RAS binding. RIN1 was also observed to inhibit cellular transformation by activated mutant RAS. This distinguishes RIN1 from other RAS effectors, which are transformation enhancing. Blockade of transformation was mediated by the RAS binding domain but required membrane localization. RIN1 recognizes endogenous RAS following transient activation by epidermal growth factor, and a portion of RIN1 fractionates to the cell membrane in a manner consistent with a reversible interaction. RIN1 also binds to 14-3-3 proteins through a sequence including serine 351. Mutation of this residue abolished the 14-3-3 binding capacity of RIN1 and led to more efficient blockade of RAS-mediated transformation. The mutant protein, RIN1(S351A), showed a shift in localization to the plasma membrane. Serine 351 is a substrate for protein kinase D (PKD [also known as PKCmu]) in vitro and in vivo. These data suggest that the normal localization and function of RIN1, as well as its ability to compete with RAF, are regulated in part by 14-3-3 binding, which in turn is controlled by PKD phosphorylation. PMID- 11784869 TI - Essential role for the lymphostromal plasma membrane Ly-6 superfamily molecule thymic shared antigen 1 in development of the embryonic adrenal gland. AB - Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system. TSA-1 is also expressed in other nonhematopoietic tissues, in particular, embryonic and adult adrenal glands. To address the function of TSA 1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting. Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities. We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline. We conclude that TSA-1 is required for normal embryonic development but that deletion of its expression does not obviously impair lymphoid development. PMID- 11784868 TI - The nuclear receptor Nor-1 is essential for proliferation of the semicircular canals of the mouse inner ear. AB - Nor-1 belongs to the nur subfamily of nuclear receptor transcription factors. The precise role of Nor-1 in mammalian development has not been established. However, recent studies indicate a function for this transcription factor in oncogenesis and apoptosis. To examine the spatiotemporal expression pattern of Nor-1 and the developmental and physiological consequences of Nor-1 ablation, Nor-1-null mice were generated by insertion of the lacZ gene into the Nor-1 genomic locus. Disruption of the Nor-1 gene results in inner ear defects and partial bidirectional circling behavior. During early otic development, Nor-1 is expressed exclusively in the semicircular canal forming fusion plates. After formation of the membranous labyrinth, Nor-1 expression in the vestibule is limited to nonsensory epithelial cells localized at the inner edge of the semicircular canals and to the ampullary and utricular walls. In the absence of Nor-1, the vestibular walls fuse together as normal; however, the endolymphatic fluid space in the semicircular canals is diminished and the roof of the ampulla appears flattened due to defective continual proliferative growth of the semicircular canals. PMID- 11784870 TI - RAD1 controls the meiotic expansion of the human HRAS1 minisatellite in Saccharomyces cerevisiae. AB - Minisatellite DNA is repetitive DNA with a repeat unit length from 15 to 100 bp. While stable during mitosis, it destabilizes during meiosis, altering both in length and in sequence composition. The basis for this instability is unknown. To investigate the factors controlling minisatellite stability, a minisatellite sequence 3' of the human HRAS1 gene was introduced into the Saccharomyces cerevisiae genome, replacing the wild-type HIS4 promoter. The minisatellite tract exhibited the same phenotypes in yeast that it exhibited in mammalian systems. The insertion stimulated transcription of the HIS4 gene; mRNA production was detected at levels above those seen with the wild-type promoter. The insertion stimulated meiotic recombination and created a hot spot for initiation of double strand breaks during meiosis in the regions immediately flanking the repetitive DNA. The tract length altered at a high frequency during meiosis, and both expansions and contractions in length were detected. Tract expansion, but not contraction, was controlled by the product of the RAD1 gene. RAD1 is the first gene identified that controls specifically the expansion of minisatellite tracts. A model for tract length alteration based on these results is presented. PMID- 11784871 TI - Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. AB - Class Ia phosphoinositide (PI) 3-kinase is a central component in growth factor signaling and is comprised of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85alpha gene (Pik3r1). Optimal signaling through the PI 3-kinase pathway depends on a critical molecular balance between the regulatory and catalytic subunits. In wild-type cells, the p85 subunit is more abundant than p110, leading to competition between the p85 monomer and the p85-p110 dimer and ineffective signaling. Heterozygous disruption of Pik3r1 results in increased Akt activity and decreased apoptosis by insulin like growth factor 1 (IGF-1) through up-regulated phosphatidylinositol (3,4,5) triphosphate production. Complete depletion of p85alpha, on the other hand, results in significantly increased apoptosis due to reduced PI 3-kinase-dependent signaling. Thus, a reduction in p85alpha represents a novel therapeutic target for enhancing IGF-1/insulin signaling, prolongation of cell survival, and protection against apoptosis. PMID- 11784872 TI - Diet and kidney stones. PMID- 11784873 TI - Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. AB - BACKGROUND: A low-calcium diet is recommended to prevent recurrent stones in patients with idiopathic hypercalciuria, yet long-term data on the efficacy of a low-calcium diet are lacking. Recently, the efficacy of a low-calcium diet has been questioned, and greater emphasis has been placed on reducing the intake of animal protein and salt, but again, long-term data are unavailable. METHODS: We conducted a five-year randomized trial comparing the effect of two diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Sixty men were assigned to a diet containing a normal amount of calcium (30 mmol per day) but reduced amounts of animal protein (52 g per day) and salt (50 mmol of sodium chloride per day); the other 60 men were assigned to the traditional low-calcium diet, which contained 10 mmol of calcium per day. RESULTS: At five years, 12 of the 60 men on the normal-calcium, low-animal-protein, low-salt diet and 23 of the 60 men on the low-calcium diet had had relapses. The unadjusted relative risk of a recurrence for the group on the first diet, as compared with the group on the second diet, was 0.49 (95 percent confidence interval, 0.24 to 0.98; P=0.04). During follow-up, urinary calcium levels dropped significantly in both groups by approximately 170 mg per day (4.2 mmol per day). However, urinary oxalate excretion increased in the men on the low-calcium diet (by an average of 5.4 mg per day [60 micromol per day]) but decreased in those on the normal-calcium, low animal-protein, low-salt diet (by an average of 7.2 mg per day [80 micromol per day]). CONCLUSIONS: In men with recurrent calcium oxalate stones and hypercalciuria, restricted intake of animal protein and salt, combined with a normal calcium intake, provides greater protection than the traditional low calcium diet. PMID- 11784874 TI - Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. AB - BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. METHODS: We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. RESULTS: The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. CONCLUSIONS: Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer. PMID- 11784875 TI - Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. AB - BACKGROUND: We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer. METHODS: A total of 1207 patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel. RESULTS: The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3, 4, or 5 renal toxicity (in 9 percent of patients, vs. 3 percent of those treated with cisplatin plus paclitaxel). Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1. CONCLUSIONS: None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer. PMID- 11784876 TI - Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. AB - BACKGROUND: Progressive osseous heteroplasia (POH), an autosomal dominant disorder, is characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue. Occasional reports of mild heterotopic ossification in Albright's hereditary osteodystrophy (AHO) and a recent report of two patients with AHO who had atypically extensive heterotopic ossification suggested a common genetic basis for the two disorders. AHO is caused by heterozygous inactivating mutations in the GNAS1 gene that result in decreased expression or function of the alpha subunit of the stimulatory G protein (Gsalpha) of adenylyl cyclase. METHODS: We tested the hypothesis that GNAS1 mutations cause POH, using the polymerase chain reaction to amplify GNAS1 exons and exon-intron boundaries in 18 patients with sporadic or familial POH. RESULTS: Heterozygous inactivating GNAS1 mutations were identified in 13 of the 18 probands with POH. The defective allele in POH is inherited exclusively from fathers, a result consistent with a model of imprinting for GNAS1. Direct evidence that the same mutation can cause either POH or AHO was observed within a single family, in which the phenotype correlated with the parental origin of the mutant allele. CONCLUSIONS: Paternally inherited inactivating GNAS1 mutations cause POH. This finding extends the range of phenotypes derived from haplo insufficiency of GNAS1, provides evidence that imprinting is a regulatory mechanism for GNAS1 expression, and suggests that Gsalpha is a critical negative regulator of osteogenic commitment in nonosseous connective tissues. PMID- 11784877 TI - Images in clinical medicine. Bronchoalveolar-cell carcinoma. PMID- 11784878 TI - Post-traumatic stress disorder. PMID- 11784879 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 1-2002. A 24-year-old woman with paresthesias and muscle cramps after a stay in Africa. PMID- 11784880 TI - Recurrent hypercalciuric nephrolithiasis--does diet help? PMID- 11784881 TI - Lung cancer--time to move on from chemotherapy. PMID- 11784882 TI - The genetic basis of progressive osseous heteroplasia. PMID- 11784883 TI - Post-traumatic stress disorder. PMID- 11784884 TI - Uterine rupture among women with a prior cesarean delivery. PMID- 11784885 TI - Radiotherapy for rectal cancer. PMID- 11784886 TI - Pulmonary embolism associated with air travel. PMID- 11784887 TI - Bilateral ovarian dermoid cysts. PMID- 11784888 TI - Use of a proton-pump inhibitor for metabolic disturbances associated with anorexia nervosa. PMID- 11784889 TI - IL-23: a cytokine that acts on memory T cells. AB - The newly discovered cytokine interleukin (IL)-23 shares some in vivo functions with IL-12, including the activation of the transcription factor STAT4 (signal tranducer and activator of transcription-4). Indeed, the receptors for each appear to share one subunit, but also have at least one distinct subunit. Frucht discusses the similarities of IL-12 and IL-23 and the effects that distinguish one from the other. In contrast to IL-12, IL-23 appears to participate in the proliferative signal in memory T cells. More functions that distinguish IL-23 from IL-12 are likely to be uncovered as soon as the other component(s) of the IL 23 receptor are molecularly cloned and characterized. PMID- 11784890 TI - Unexpected cross talk: small GTPase regulation of calcium channel trafficking. AB - Calcium ions can serve as both charge carriers and second messengers. Most cells have voltage-dependent calcium channels that control the membrane permeability to calcium. These channels at the membrane open in response to changes in membrane potential. Their activity is further modulated by phosphorylation by various kinases, such as protein kinase A and protein kinase C, and by changes in intracellular calcium concentration through the action of calcium calmodulin (Ca(2+)/CaM). Trimmer discusses a potential mechanism by which the expression of these channels can be regulated through an interaction with a small guanosine triphosphatase (GTPase), kir/Gem, that influences trafficking of the channels through effects on assembly with auxiliary subunits that occurs in the biosynthetic pathway. PMID- 11784891 TI - [Evaluation of collective health graduate education in brazil]. PMID- 11784892 TI - [Tropics of risk discourse: risk-adventure as a metaphor in late modernity]. AB - This article discusses new uses of interpretative repertoires of risk, especially those related to adventure. The author argues that the language of risk as adventure has multiple uses, as both a hedge against de-traditionalizing processes typical of late modernity and a figure of speech for new sensitivities stemming from the imperative of coping with the imponderability and volatility of modern risks. The article begins with an overview of the historical meanings of risk, seeking to argue that, as language in use, risk is a useful vantage point for understanding the transformations currently under way in the forms of social control, suggesting that we are experiencing a transition from disciplinary society, typical of classic modernity, to risk society. The discussion then focuses on recent transformations in images of risk, with special emphasis on the trend to use risk-adventure as a metaphor for late modernity. PMID- 11784893 TI - [Association between dietary factors and brain tumors in adults: a review]. AB - This paper reviews the scientific literature published from 1986 to 1999 assessing the relationship between dietary factors and brain tumors in adults. The work aimed to describe the estimated associations and to discuss methodological aspects that might influence the results. The studies generally appear to show a moderate association between dietary factors and brain tumors. There is evidence that N-nitroso compounds enhance the risk of developing such tumors and that consumption of fruits and vegetables can inhibit them. Use of proxies in most of the studies may have introduced bias, thereby contributing to some inconsistent observations. Epidemiological research on diet and brain tumors should consider other components of food besides N-nitroso compounds. It is important to carefully assess exposure periods and to prevent bias related to control selection and recall. PMID- 11784894 TI - [Acid mist occupational exposure and oral disease: a review]. AB - This study is a review of published research findings on the oral effects of occupational exposure to acid mists. A literature search was conducted on MEDLINE, LILACS, SciELO, BBO, and DEDALUS, identifying eight articles and a doctoral dissertation focusing on this association. Findings were consistent with a positive association between occupational exposure to acid mists and dental erosion, according to the literature published since 1919. Studies on the association between acid mist exposure in the workplace and periodontal disease, or oral mucous lesions, were more recent and scarce, and their findings remain controversial. Several methodological drawbacks were observed, such as small sampling size and poorly developed analysis, as exemplified by little or no attention to confounding variables. These findings support the relevance of this research area and the need for improved research design. They also highlight the importance of considering oral health as a component of workers' health in effective preventive programs. PMID- 11784895 TI - The Bambui Health and Aging Study (BHAS): factors associated with hospitalization of the elderly. AB - This study aimed to identify factors associated with hospital admissions of the elderly. All residents of Bambui, Minas Gerais State >/= 60 years (n = 1,742) were selected. Some 1,606 of these (92.2%) participated in the study. The dependent variable was the number of hospital admissions (none, one, and two or more) during the previous 12 months. Independent variables were grouped as enabling, predisposing, and need-related factors. The strongest associations with multiple hospital admissions were: living alone; financial constraints to purchase of medication; and various indicators of need (worse self-perceived health, more visits to physician, greater use of prescription medications, and history of coronary heart disease). Such variables could help identify older adults at greatest risk and thus prevent hospitalization. PMID- 11784896 TI - [Factors contributing to the development of community-acquired infections in type 2 diabetics admitted to the Cayetano Heredia National Hospital]. AB - This study aims to identify factors contributing to the development of community acquired infections in hospitalized type-2 diabetics, using an unmatched case control design. A total of 105 pairs of diabetic patients with community-acquired infections as compared to non-infectious diseases, respectively, were chosen randomly from the discharge registry of the clinical wards of a teaching hospital from 1991 to 1998. Bivariate and multivariate analysis was conducted with estimation of the adjusted odds ratio. According to stratified analysis controlling for age and sex, autonomic neuropathy proved to be a contributing factor to development of urinary tract infections (OR = 4.07). In the multivariate model, peripheral vasculopathy was isolated (R2: 0.24) as a contributing factor in the development of soft-tissue infections (OR = 6.79). Confidence intervals were significant at 0.05. In conclusion, peripheral vasculopathy and neurogenic bladder contribute to the development of community acquired infections in hospitalized type-2 diabetics. PMID- 11784897 TI - Assessment of weight gain during pregnancy in general prenatal care services in Brazil. AB - Obesity is an emerging major health risk for women around the world. In this regard, little attention has been given to pregnancy, a moment of risk not only for major weight gain in these women, but also for macrosomia in their offspring. The objective of this study is to evaluate weight gain during pregnancy. Data pertains to a cohort of pregnant women attending general prenatal care clinics in six state capitals in Brazil, from 1991 to 1995. We studied women aged 20 years and over with singleton pregnancies and no diagnosis of diabetes outside pregnancy, enrolled at approximately 20 - 28 weeks of gestation. According to the Institute of Medicine criteria, 38% (95%CI: 36-40%) of the women studied gained less and 29% (95%CI: 28-31%) had more than the recommended total weight gain. These proportions vary according to pre-pregnancy nutritional status. Given the increasing epidemic of obesity, the high prevalence of overweight and obesity in Brazilian women prior to pregnancy, and the lack of achievement of recommended weight gain during pregnancy, more effective means of managing weight gain during pregnancy are necessary. PMID- 11784898 TI - [Rural work-related accidents in Pelotas, Rio Grande do Sul State, Brazil: a population-based cross-sectional study]. AB - Epidemiological literature on occupational accidents among rural workers is scarce in Brazil. This population-based cross-sectional study was designed to investigate the characteristics of farming accidents occurring in the rural area of Pelotas, Southern Brazil. A multi-stage sampling scheme was used to select a representative sample of farms. From January to April 1996, a total of 258 rural families were visited, and all 580 rural workers identified in these families answered a standardized questionnaire. Sixty-three rural workers (11%) reported at least one work-related accident in the previous twelve months. There were 82 accidents during the study period, mainly related to the use of hand farm tools (29%) and handling farm animals (27%). The main types of injuries were cuts (50%), bruises (13%), and burns (9%). The body areas most frequently involved were hands (34%), feet (29%), and legs (18%). Among the injured rural workers, only 32% used health services to treat the resulting lesions (46% went to primary health care facilities and 36% to emergency services). PMID- 11784899 TI - Anogenital warts in children: sexual abuse or unintentional contamination? AB - Anogenital warts (AGW) were recently recognized in children, and their significance as an index of childhood sexual abuse is controversial. We report our transdisciplinary approach (including a pediatric surgeon, psychologist, social worker, ethics expert, and occasionally law enforcement agents) and its results in a group of 17 children with AGW treated at the public pediatric referral hospital in Rio de Janeiro, Brazil, during a 3-year period (1996-1999). All children were treated by electrocauterization of the warts, tested for other STDs, and submitted to perineal examination under anesthesia. Families received psycho-social counseling as necessary and cases were referred to child protection and law enforcement agents when indicated according to Brazilian legislation. We identified a high incidence of sexual abuse (8 children, 5/7 > 5 years old), with 3 patients inconclusive as to sexual abuse and 7 cases of perinatal transmission (5/8 < 4 years old). We conclude that AGW are indeed a strong sign of suspicion for sexual abuse in children, especially but not exclusively > 5 years of age. However, strong support and a transdisciplinary approach to the children and their families is necessary to identify it. PMID- 11784900 TI - [Reliability of diagnostic instruments: investigating the psychiatric DSM-III checklist applied to community samples]. AB - This study focused on the reliability of the DSM-III inventory of psychiatric symptoms in representative general population samples in three Brazilian cities. Reliability was assessed through two different designs: inter-rater reliability and internal consistency. Diagnosis of lifetime (k = 0.46) and same-year generalized anxiety (k = 1.00), lifetime depression (k = 0.77), and lifetime alcohol abuse and dependence (k = 1.00) was consistently reliable in the two methods. Lifetime diagnosis of agoraphobia (k = 1.00), simple phobia (k = 0.77), non-schizophrenic psychosis (k = 1.00), and psychological factors affecting physical health (1.00) showed excellent reliability as measured by the kappa coefficient. The main reliability problem in general population studies is the low prevalence of certain diagnoses, resulting in small variability in positive answers and hindering kappa estimation. Therefore it was only possible to examine 11 of 39 diagnoses in the inventory. We recommend test and re-test methods and a short time interval between interviews to decrease the errors due to such variations. PMID- 11784901 TI - [The various meanings of Brazil's certification as free of Chagas disease]. AB - The article discusses Brazil's recent certification as free of Chagas disease transmission by Triatoma infestans, analyzing the various meanings ascribed to this position. Resulting mainly from measures by both the Chagas Disease Control Program (PCDCh) established in Brazil in 1975 and the Southern Cone Initiative launched in 1991, this certification has been interpreted in ways that lead to confusion between the elimination of Chagas disease transmission by T. infestans and eradication of the disease. The present status of vector transmission control in Brazil is discussed, with emphasis on the Northeast, in most States of which T. infestans is not the main species involved in transmission. The article highlights the need to broaden the discussion of the readings and consequences involved in the present control achievements in light of possible harm from misinterpretations that might jeopardize further efforts to control the disease. PMID- 11784902 TI - Perinatal health and mother-child health care in the municipality of Sao Luis, Maranhao State, Brazil. AB - The purpose of this article was to evaluate socioeconomic and demographic indicators, reproductive health, use of prenatal, childbirth, and neonatal services, and anthropometric data for mothers and infants. The authors performed a cross-sectional analysis of a systematic sample of 2,831 hospital births in Sao Luis, Maranhao State, from March 1997 to February 1998 at ten public and private maternity hospitals. The sample was stratified proportionally according to the number of births in each maternity hospital. Mothers answered a standard questionnaire. Of the total, 97.9% were live births and 98% were singletons. Prenatal coverage was 89.5%, and prevalence of cesarean sections was 33.8%. A physician provided prenatal care in 75.7% of cases and performed 73.8% of the deliveries. The Unified Health System covered the costs of 76.4% of the prenatal visits and 89.7% of the deliveries. A pediatrician was present in the delivery room in 50.2% of cases. The low birth weight rate was 9.6% and the preterm birth rate 13.9%. Reasons for concern included a high percentage of adolescent mothers, single mothers (or without partners), the high cesarean rate, and the high percentage of births attended by unqualified personnel. PMID- 11784903 TI - [Body mass index and its relationship to nutritional and socioeconomic variables: a linear regression approach to a Brazilian adult sub-population]. AB - This paper focuses on the relationship between body mass index (BMI) and family energy intake, occupational energy expenditure, per capita family expenditure, sex, age, and left arm circumference for a group of Brazilian adults randomly selected among those interviewed for a survey on food consumption and family budgets, called the National Family Expenditure Survey. The authors discuss linear regression methodological issues related to treatment of outliers and influential cases, multicollinearity, model specification, heteroscedasticity, as well as the use of two-level variables derived from samples with complex design. The results indicate that the model is not affected by outliers and that there are no significant specification errors. They also show a significant linear relationship between BMI and the variables listed above. Although the hypothesis tests indicate significant heteroscedasticity, its corrections did not significantly change the model's parameters, probably due to the sample size (14,000 adults), making hypothesis tests more rigorous than desired. PMID- 11784904 TI - [Association between socioeconomic factors and infant deaths due to diarrhea, pneumonia, and malnutrition in a metropolitan area of Southeast Brazil: a case control study]. AB - A population-based case-control study was carried out to identify determinant factors for post-neonatal infant deaths due to diarrhea, pneumonia, and malnutrition in Greater Metropolitan Belo Horizonte, Southeast Brazil. From May 1, 1991, to April 30, 1992, 511 post-neonatal deaths due to diarrhea, pneumonia, and malnutrition were selected after investigation of medical records to validate cause of death. Of this total, 396 deaths were compared to a neighborhood control group, matched for age. The study was carried out in a low-income area with a high proportion of families living in shantytowns. The article discusses the methodology and selected socioeconomic factors. Logistic regression analysis indicated that number of household appliances, mother's and father's education, and mother's marital and work status were significantly associated with risk of infant death, i.e., they were determinants of infant deaths due to avoidable causes. PMID- 11784905 TI - [Traffic accidents in a city in Southern Brazil: an evaluation of coverage and quality of data]. AB - The aim of this study was to analyze police coverage and the validity of data on emergency and hospitalization records as well as on death certificates for traffic casualties in Londrina, Parana State, Brazil. Victims (3,643) of road accidents during the first semester of 1996 were investigated and followed up after 180 days to confirm whether death was due to the accident. Police data recorded only 32.5% of the casualties, the coverage being higher for car occupants (71.6%) and lower for cyclists (8.1%) and pedestrians (24.8%). Agreement was low between original information and that derived from investigation of death certificates (Kappa coefficient 0.10; 95% CI: 0.02-0.17), fair for hospitalization records (Kappa coefficient 0.33; 95% CI: 0.27-0.40), and substantial for emergency records (Kappa coefficient 0.63; 95% CI: 0.61-0.65). Results suggest that police data underestimate the number of traffic casualties and that it is necessary to improve the validity of medical records. PMID- 11784906 TI - [Access to food stamps and nutritional status of adults from Northeast and Southeast Brazil, 1997]. AB - Access by adults (>/=20 years of age) to the Workers' Food Program was investigated in a probabilistic sample of the Brazilian population living in the Northeast and Southeast regions. Only 19.9% (Northeast = 11.7% and Southeast = 24.9%) of the working population were beneficiaries of the Program. Receiving the benefit increased in direct proportion to income in both regions, but with a huge gap in the NE: 19.% of individuals in the 5th income quintile and only 3.6% in the 1st quintile were beneficiaries of the Program. Overweight (BMI >/= 25kg.m( 2)) was more prevalent (38.5%) than underweight (BMI < 18.5). Underweight was more prevalent in women (6.1%) than men (3.4%). More overweight than underweight individuals were beneficiaries of the Program (31.7 and 23.5%, respectively). These data indicate that the Program fails to provide food supplementation to the most needy workers in the two regions of Brazil, i.e., its original target population. PMID- 11784907 TI - [Socioeconomic and demographic indicators and nutritional status of children in a rural land settlement in Rio de Janeiro]. AB - This study evaluated socioeconomic indicators and nutritional status in 201 children and adolescents in a rural land settlement in Sao Jose da Boa Morte, Rio de Janeiro. Nutritional deficit was defined as a value below -2 z score for the reference median from the National Center for Health Statistics (NCHS) for weight for-age (W/A) and stature-for-age (S/A) for children under five years of age and weight-for-stature (W/S) and S/A for children from 5.0 to 9.9 years. For adolescents, the study used cut-off points at the 5th percentile (thin) and 85th percentile (overweight) from the distribution of body mass index (BMI) in the Brazilian population. According to the study, 53.8% of the households had 4 to 6 members, 34.5% had rudimentary cesspools, 31.2% had no running water, 11.0% had no bathroom, 58.2% burned or buried their garbage, and 13.6% of the mothers were illiterate. No case of nutritional deficit was found in the 0-4.9 year age bracket, and in the 5-9.9 year bracket there were one underweight and three overweight children. The authors concluded that the low prevalence of nutritional deficits in the study group, despite the exposure to risk factors, may be related to the presence of protective factors like access to health services, and that there was an important rate of overweight among adolescents (13.3%). PMID- 11784908 TI - [HIV, HPV, and syphilis prevalence in a women's penitentiary in the city of Sao Paulo, 1997-1998]. AB - Incarcerated women as a group are particularly vulnerable to infections. The lack of public programs for prevention, early diagnosis, and treatment contribute to the increase in the incidence and prevalence of diseases in general and especially sexually transmitted diseases. This article aims to estimate the prevalence of infection by the human immunodeficiency virus (HIV), human papillomavirus (HPV), and syphilis among inmates at the Women's Penitentiary in the State capital of Sao Paulo, Brazil. All inmates were invited to participate in the study, which was divided into two stages: 1. STD/AIDS preventive workshops including interviews and 2. laboratory tests. The interview covered knowledge of STD/AIDS, risk behavior, and individual reproductive health history. A total of 262 women, with a mean age of 32.4 years and limited schooling, participated in more than one stage of the study. Prevalence rates were 14.5% for HIV, 16.3% for high-oncogenic-risk HPV probes, 4.8% for low-oncogenic-risk HPV probes, and 5.7% for syphilis. The authors conclude that STD/HIV constitute a serious health problem in the prison system, requiring urgent preventive measures. PMID- 11784909 TI - [Arterial hypertension among oil-drilling workers exposed to noise]. AB - A cross-sectional study with a retrospective component was conducted to evaluate occupational noise exposure as a potential risk factor for arterial hypertension among 775 workers from an oil-drilling industry. Hypertension was defined as >/= 140/90mmHg. Occupational noise exposure was measured as: (1) exposure to sound pressure levels >/= 85dbA for 10 years or more and (2) moderate-to-severe noise induced hearing loss (NIHL). The effects of age, education, shift work, and obesity were evaluated by stratification and logistic regression analysis. A positive association between occupational noise exposure and hypertension was found, using both the level/duration of noise exposure (RP = 1.8; 95% CI: 1.3 2.4) and NIHL (RP = 1.5; 95% CI: 1.1-2.0) as exposure indicators. Considering the study limits, long-term occupational noise exposure thus appears to be a risk factor for arterial hypertension. PMID- 11784910 TI - [Changes in the Declaration of Helsinki: economic fundamentalism, ethical imperialism and social control]. AB - This study is a critical reflection on attempts to alter the Declaration of Helsinki, a key document of the democratic theses achieved in the latter half of the 20th century and thus a legacy for humanity because of its ethical guidelines for research involving human beings. Therefore, there must be worldwide social control over such a document, and any change in it demands ample debate with international participation to avoid any reversal in its humanitarian thrust. The study analyzes current aspects of research with human subjects in so-called "outlying" or "developing" countries. It also brings a social and political focus to the matter, highlighting that the economic fundamentalism exercised by wealthy countries inevitably leads to an ethical imperialism, exposing communities of poor countries to even greater vulnerability, discrimination, and social exclusion. PMID- 11784911 TI - [Prevalence of canine filariasis by Dirofilaria immitis and Dipetalonema reconditum in Maceio, Alagoas State, Brazil]. AB - A survey on the prevalence of Dirofilaria immitis and Dipetalonema reconditum was conducted in 1,519 dogs from Maceio and two coastal areas in the State of Alagoas, Northeast Brazil, from 1995 to 1999, by testing for microfilariae in blood. All blood samples were from exclusively domiciled dogs with a known history, showing that the infections were autochthonous, confirming transmission of canine filariasis in these areas. In Greater Metropolitan Maceio, 15 (1.3%) microfilaremic dogs were detected with D. immitis and 15 (1,3%) with D. reconditum. In the southern coastal area there was an estimated prevalence of 12.7% for D. immitis. D. immitis and D. reconditum microfilaria were 298.1 micrometer and 249.2 micrometer long and 7.3 micrometer and 4.4 micrometer wide, respectively. A Witness immunotest that detects D. immitis antigen was used to confirm parasitological results and reveal occult dirofilariasis cases. Of the total 6,579 females examined, 8 (0.1%) Culex quinquefasciatus were observed to be naturally infected with D. immitis larvae. These results proved dirofilariasis transmission in Maceio and demonstrated D. reconditum in the same geographic area. PMID- 11784912 TI - [A biographical profile of Nelson Chaves and his contribution to nutrition in public health in Brazil]. AB - This study focuses on the academic and intellectual career of scientist Nelson Chaves, founder of the Nutritionists School and the Institute of Nutrition at the Federal University in Pernambuco. The methodology was based on quantitative and qualitative analyses of this author's scientific production, published from 1932 to 1982. Beginning with his search for solutions to malnutrition children from the Zona da Mata region in Pernambuco, this scientist created what is commonly called the humanist-ecological paradigm of the Brazilian nutritional issue, thus contributing to the institutionalization of the field of nutrition in public health throughout Brazil. PMID- 11784914 TI - [Smallpox, an old foe]. AB - Smallpox has accompanied mankind for centuries, causing deaths and permanent lesions. Used in the past as a biological weapon during wars, it has come into focus again precisely because of this renewed possibility, although the disease has been eradicated in the Americas since 1971 and worldwide since 1977. Data gathered during the eradication campaigns show that the disease spread relatively slowly through close contacts between patients and susceptibles. Sub-clinical infection in non-vaccinated individuals was a rare event, and blockade vaccination surrounding new cases (as long as these cases were confirmed early) was able to prevent the disease from spreading in the community. Even with only one dose, vaccinated individuals rarely developed a serious case of the disease upon reinfection. The use of smallpox as a biological weapon should be considered a real possibility, although according to the available data, highly virulent viral suspensions spread very close to the target population would be necessary to infect a large number of persons. PMID- 11784913 TI - [Biological warfare, bioterrorism and public health]. AB - Biological agents as weapons are not new to mankind. For centuries and into the present, biological warfare has been the subject of much research and speculation, but little action. Their limited use has probably been due to fear of unexpected counter-effects and doubts about their efficiency as weapons. Recently a new form of terrorism employing infectious agents has emerged slowly and without much fanfare, until the recent events with Bacillus anthracis in the United States. Smallpox is potentially the most devastating of these agents. Less than 25 years after the eradication of smallpox, the public health field is now forced to deal with the possibility of its re-introduction. The author discusses the scenario of smallpox re-introduction into Brazil. PMID- 11784915 TI - Common vampire bat attacks on humans in a village of the Amazon region of Brazil. AB - Many people in Amazonian communities have reported bat bites in the last decade. Bites by vampire bats can potentially transmit rabies to humans. The objective of this study was to analyze factors associated with bat biting in one of these communities. A cross-sectional survey was conducted in a village of gold miners in the Amazonian region of Brazil (160 inhabitants). Bats were captured near people's houses and sent to a lab. Of 129 people interviewed, 41% had been attacked by a bat at least once, with 92% of the bites located on the lower limbs. A logistic regression found that adults were bitten around four times more often than children (OR = 3.75, CI 95%: 1.46-9.62, p = 0.036). Males were bitten more frequently than females (OR = 2.08, CI 95%: 0.90-4.76, p = 0.067). Nine Desmodus rotundus and three frugivorous bats were captured and tested negative for rabies. The study suggests that, in an area of gold miners, common vampire bats are more likely to attack adults and males. The control strategy for human rabies developed in this region should therefore place special emphasis on adult males. There should also be more research on how the search for gold in the Amazonian region places people and the environment at risk. PMID- 11784916 TI - [Risk factors for breast cancer among rural Terena Indian women in the State of Mato Grosso do Sul, Brazil]. AB - In order to evaluate the distribution of selected risk factors for breast cancer among Terena Indian women in the State of Mato Grosso do Sul, Brazil, two samples were interviewed, respectively, in 1995 (330 women from ten Indian villages) and 1997 (40 women from the Limao Verde village). Reproductive history, diet characteristics, and family and personal medical history were investigated and body mass index was measured. In the larger sample, mean age at menarche was 12.3 years (30% at 13 years old or later), 86% of women reported one or more pregnancies (42% reporting 5 or more), 71% reported three or more pregnancies, mean age at first pregnancy was 18.9 years (3.8% after 28 years), mean duration of breastfeeding was 84 months, and 70% reported menopause before age 50. Dietary pattern in the smaller sample revealed a high intake of fruits, vegetables, pasta, and tubers and scarce intake of red meat and chicken; 50 of the women (95% CI: 34.1-65.9) presented overweight (BMI 25-29) and 27% (95% CI: 15.1-44.1) obesity (BMI > 29). PMID- 11784917 TI - [Dental mutilation: rural workers' concepts of responsibility for tooth loss]. AB - Brazilian oral hygiene institutions have promoted tooth extraction as a dental health practice. This article investigates the issue of dental loss within a rural drought area in the State of Bahia. Based on verbal information provided by local inhabitants, the author investigates dental extraction as perceived by the community, i.e., as a commonplace fact. The main goal is to analyze both representations of the oral cavity based on individual experiences and their associations with oral care practices, derived from the social reality in which they are immersed. The author considers the issues of both individual responsibility and that of government agencies and dentists. PMID- 11784918 TI - In honor to Herman Lent's 90 years and to his major contributions to the Memorias do Instituto Oswaldo Cruz. PMID- 11784919 TI - The search for new antimalarial drugs from plants used to treat fever and malaria or plants ramdomly selected: a review. AB - In this review we discuss the ongoing situation of human malaria in the Brazilian Amazon, where it is endemic causing over 610,000 new acute cases yearly, a number which is on the increase. This is partly a result of drug resistant parasites and new antimalarial drugs are urgently needed. The approaches we have used in the search of new drugs during decades are now reviewed and include ethnopharmocology, plants randomly selected, extracts or isolated substances from plants shown to be active against the blood stage parasites in our previous studies. Emphasis is given on the medicinal plant Bidens pilosa, proven to be active against the parasite blood stages in tests using freshly prepared plant extracts. The anti-sporozoite activity of one plant used in the Brazilian endemic area to prevent malaria is also described, the so called "Indian beer" (Ampelozizyphus amazonicus, Rhamnaceae). Freshly prepared extracts from the roots of this plant were totally inactive against blood stage parasites, but active against sporozoites of Plasmodium gallinaceum or the primary exoerythrocytic stages reducing tissue parasitism in inoculated chickens. This result will be of practical importance if confirmed in mammalian malaria. Problems and perspectives in the search for antimalarial drugs are discussed as well as the toxicological and clinical trials to validate some of the active plants for public health use in Brazil. PMID- 11784920 TI - Differentiation and genetic analysis of Rhodnius prolixus and Rhodnius colombiensis by rDNA and RAPD amplification. AB - Domiciliated Rhodnius prolixus and sylvatic R. colombiensis were analyzed in order to confirm their genetic divergence and verify the risk that the latter represents in the domiciliation process, and to provide tools for identifying the sources of possible reinfestation by triatomines in human dwellings allowing control programs to be undertaken. Comparison of random amplified polymorphic DNA amplification patterns and cluster analysis suggests reproductive discontinuity between the two species. The calculated statistical F value of 0.24 and effective migration rate of 0.6 individuals per generation are insufficient to maintain genetic homogeneity between them and confirm the absence of present genetic flow. R. colombiensis presents higher intrapopulation variability. Polymerase chain reaction of ribosomal DNA supports these findings. The low genetic flow between the two species implies that R. colombiensis do not represent an epidemiological risk for the domiciliary transmission of Trypanosoma cruzi in the Tolima Department. The lower variability of the domiciliated R. prolixus could result in greater susceptibility to the use of pesticides in control programs. PMID- 11784921 TI - Metazoan parasite fauna of the bigeye flounder, Hippoglossina macrops, from Northern Chile. Influence of host age and sex. AB - The metazoan parasite fauna of Hippoglossina macrops (n = 123) from northern Chile (30 degrees S) is quantitatively described for the first time, and the role of host age and sex was evaluated. Twelve parasite species were recovered, including 5 ectoparasites (2 Monogenea, 2 Copepoda and 1 Piscicolidae) and 7 endoparasites (1 Digenea, 3 Cestoda, 2 Acanthocephala, and 1 Nematoda). The copepod Holobomolochus chilensis, the monogenean Neoheterobothrium sp., the adult acanthocephalan Floridosentis sp. and the hirudinean, Gliptonobdella sp. are new geographical and host records. The most prevalent ectoparasitic species were the monogenean, Neoheterobothrium sp. and the copepod, H. chilensis. Among endoparasites, the acanthocephalans Floridosentis sp. and Corynosoma australe were most prevalent and abundant. Prevalence and mean intensity of infection for most parasitic species were not affected by host sex, however the prevalence of Floridosentis sp. was significantly greater in males. Intensity of infection was positively correlated with host age for Neoheterobothrium sp., and negatively correlated for Floridosentis sp. and H. chilensis. The helminth species richness of the host H. macrops was lower compared to related flatfishes from the Northern Hemisphere. The relationship of the helminth fauna of H. macrops, its feeding habits and ecological habitats are discussed. PMID- 11784922 TI - Plasmodium/intestinal helminth co-infections among pregnant Nigerian women. AB - Hospital based studies were conducted to investigate the occurrence of Plasmodium/intestinal helminth co-infections among pregnant Nigerian women, and their effects on birthweights, anaemia and spleen size. From 2,104 near-term pregnant women examined, 816 (38.8%) were found to be infected with malaria parasites. Among the 816 parasitaemic subjects, 394 (48.3%) were also infected with intestinal helminths, 102 (12.5%) having mixed helminth infections. The prevalence of the helminth species found in stool samples of parasitaemic subjects examined was, Ascaris lumbricoides (19.1%), hookworm (14.2%), Trichuris trichiura (7%) Schistosoma mansoni (3.4%), Enterobius vermicularis (2%), Hymenolepis sp. (1.6%) and Taenia sp. (1%). Mothers with Plasmodium infection but without intestinal helminth infection had neonates of higher mean birthweights than those presenting both Plasmodium and intestinal helminth infections and this effect was more pronounced in primigravids. The mean haemoglobin values of malarial mothers with intestinal helminth infections were lower than those with Plasmodium infection but without intestinal helminth infections but these were not statistically significant. Severe splenomegaly was predominant among parasitaemic gravidae who also harboured S. mansoni infection in two of the hospitals studied. PMID- 11784923 TI - Distribution of sand flies (Diptera: Psychodidae) at different altitudes in an endemic region of American cutaneous leishmaniasis in the State of Espirito Santo, Brazil. AB - The involvement of different sand fly species in the transmission of American cutaneous leishmaniasis (ACL) at different altitudes was evaluated in the municipality of Afonso Claudio in the State of Espirito Santo, Brazil, from November 1995 to February 1997. CDC light traps and Shannon traps baited with human volunteers were hung simultaneously at three altitudes of a river valley: (a) 650-750 m in an area of active ACL transmission; (b) 750-850 m in a transitional area; and (c) 850-950 m in an area where no ACL transmission occurred. A total of 13,363 specimens belonging to 28 species was collected. The five most abundant man-biting species were Lutzomyia intermedia, which constituted 24.3% of the total, Lu. migonei (22.3%), Lu. whitmani (15.4%), Lu. fischeri (14.9%) and Lu. monticola (5.8%). Analysis of the distribution of these species at the three altitudes provided evidence that Lu. fischeri and Lu. monticola were not involved in ACL transmission, whereas Lu. migonei and Lu. whitmani might act as secondary vectors of Leishmania (Viannia) braziliensis and Lu. intermedia was probably the principal vector of the parasite. These results reinforce those published in the existing literature, which indicate that Lu. intermedia is the main vector of Le. (V.) braziliensis in Southeast Brazil, while Lu. migonei and Lu. whitmani are of secondary importance. PMID- 11784924 TI - An outbreak of gastroenteritis associated with astrovirus serotype 1 in a day care center, in Rio de Janeiro, Brazil. AB - Between June 4th and June 20th 1996 rotavirus, adenovirus, and astrovirus (HAstrV) were investigated in fecal samples from 27 children under three years old with acute diarrhea, attending the Bertha Lutz day care center, in Rio de Janeiro. All fecal samples were analyzed by polyacrylamide gel electrophoresis (PAGE), reverse transcriptase polymerase chain reaction (RT-PCR), enzyme immunoassays (EIA), and electron microscopy (EM). Nine of them (33%) showed positive results for HAstrV by at least one of the employed methodologies. Eight were positive by RT-PCR and EIA, and six by EM. All positive samples were inoculated onto HT-29 (human colon adenocarcinoma) cultured cells for HAstrV isolation and seven were positive after three passages. The sequencing analysis of eight RT-PCR products (449 bp) from gene that codifies VP2 protein, showed a total nucleotide identity among them and 98% with HAstrV-1 (strain Oxford type 1). This is the first report of a gastroenteritis outbreak associated with HAstrv 1 in a day care center in Rio de Janeiro and it reinforces the importance of this virus in association with infantile acute gastroenteritis. PMID- 11784925 TI - Prevalence and intensity of soil-transmitted helminthiasis in the city of Portoviejo (Ecuador). AB - We studied the stool samples of 151 school children in a district of the city of Portoviejo (Ecuador) in order to determine the prevalence and intensity of soil transmitted helminthiasis (STH) and their relationships with anthropometric indices. The samples were analyzed with the semiquantitative Kato-Katz technique and the intensity of infections was categorized as light, moderate or high according to the thresholds set by the World Health Organization. Prevalence of soil transmitted helmintiasis was 65% (92 out of 141 collected samples), Ascaris lumbricoides was the most common STH (63%) followed by Trichuris trichiura (10%) and hookworm (1.4%). Heavy intensity infections were found in 8.5% of the stool samples, with T. trichiura showing higher worm burdens than A. lumbricoides. Sixteen percent of the children were below the third percentile for weight (wasted), while 27% were below the third percentile for height (stunted). A significant relationship was found between the worm burden and the degree of stunting. This study suggests that the periodic administration of an antihelminthic drug should be targeted to preschool and school children to allow a normal growth spurt and prevent stunting. PMID- 11784926 TI - The distribution of two major malaria vectors, Anopheles gambiae and Anopheles arabiensis, in Nigeria. AB - The distribution of Anopheles gambiae and An. arabiensis across the ecological zones of Nigeria (arid savanna in the north gradually turns into humid forest in the south) was investigated. Results of the present study were compared to the distributions determined from samples of indoor-resting females reported by an earlier study over 20 years ago. Larvae were sampled in the rainy seasons of 1997 and 1999 from 24 localities, 10 of which were sampled in both years. Specimens were identified by the polymerase chain reaction method. Results showed that species composition changed significantly among the 10 localities in both years (chi2=13.62, P = 0.0002), but this change was significant in only four of the 10 localities. The identity of the prevalent (more abundant) species changed between 1997 and 1999 in only three of 10 localities. An. arabiensis was prevalent in several localities in the southern Guinea savanna, an area where it was virtually absent over 20 years ago. The data suggest that An. arabiensis has extend its range, although differences in sampling technique (larval sampling versus adult collection) can not be ruled out as a possible explanation. PMID- 11784927 TI - Phlebotomine sand flies in the State of Piaui, Brazil (Diptera: Psychodidae: Phlebotominae). AB - In 1997, 1998 and 1999 we performed several captures in the State of Piaui, in the counties of Barro Duro, Campo Maior, Castelo, Floriano, Picos, Sao Raimundo Nonato and Teresina. We used CDC light traps inside houses, in a primary forest and in one cave. Seventeen species were collected being Lutzomyia longipalpis, Lutzomyia samueli, Lutzomyia whitmani and Lutzomyia lenti the most captured species. The genus Brumptomyia, L. whitmani, Lutzomyia sordellii, Lutzomyia carmelinoi, Lutzomyia termitophila, Lutzomyia peresi and Lutzomyia quinquefer are reported for first time in Piaui. We call the attention for the presence of L. whitmani and L. longipalpis, important vectors of leishmaniasis in various regions of South America. PMID- 11784928 TI - Wing geometry as a tool for studying the Lutzomyia longipalpis (Diptera: Psychodidae) complex. AB - Toro Toro (T) and Yungas (Y) have been described as genetically well differentiated populations of the Lutzomyia longipalpis (Lutz & Neiva, 1912) complex in Bolivia. Here we use geometric morphometrics to compare samples from these populations and new populations (Bolivia and Nicaragua), representing distant geographical origins, qualitative morphological variation ("one-spot" or "two-spots" phenotypes), ecologically distinct traits (peridomestic and silvatic populations), and possibly different epidemiological roles (transmitting or nor transmitting Leishmania chagasi). The Nicaragua (N) (Somotillo) sample was "one spot" phenotype and a possible peridomestic vector. The Bolivian sample of the Y was also "one-spot" phenotype and a demonstrated peridomestic vector of visceral leishmaniasis (VL). The three remaining samples were silvatic, "two-spots" phenotypes. Two of them (Uyuni and T) were collected in the highlands of Bolivian where VL never has been reported. The last one (Robore, R) came from the lowlands of Bolivia, where human cases of VL are sporadically reported. The decomposition of metric variation into size and shape by geometric morphometric techniques suggests the existence of two groups (N/Y/R, and U/T). Several arguments indicate that such subdivision of Lu. longipalpis could correspond to different evolutionary units. PMID- 11784929 TI - Digenea and acanthocephala of elasmobranch fishes from the southern coast of Brazil. AB - New records for helminth species recovered from elasmobranch fishes in Brazil are established. Digenean and acanthocephalan parasites of elasmobranch fishes are reported from the southern coast of Brazil: Otodistomum veliporum (Creplin, 1837) Stafford, 1904 (Digenea: Azygiidae) in the stomach and spiral valve of Dipturus trachydermus and in the spiral valve of Squatina sp. Cystacanths and juveniles of the acanthocephalans Corynosoma australe Johnston, 1937 and Corynosoma sp., in the spiral valve of Squatina sp., Galeorhinus galeus and Hexanchus griseus and in the stomach of Squalus megalops; a juvenile of Gorgorhynchus sp., in the spiral valve of Sphyrna zygaena. Dipturus trachydermus and Squatina sp. are new host records for O. veliporum. Digeneans and acanthocephalans are reported for the first time parasitizing elasmobranch fishes in Brazil. PMID- 11784930 TI - External morphology of sensory structures of fourth instar larvae of neotropical species of phlebotomine sand flies (Diptera: Psychodidae) under scanning electron microscopy. AB - In the present study, some morphological structures of antennae, maxillary palps and caudal setae of fourth instar larvae of laboratory-reared phlebotomine sand flies (Lutzomyia longipalpis, L. migonei, L. evandroi, L. lenti, L. sericea, L. whitmani and L. intermedia) of the State of Ceara, Brazil, were examined under scanning electron microscopy. The antennal structures exhibited considerable variation in the morphology and position. A prominent digitiform distal segment has been observed only on the antenna of species of the subgenus Nyssomyia. The taxonomic relevance of this and other antennal structure is discussed. The papiliform structures found in the maxillae and the porous structures of the caudal setae of all species examined may have chemosensory function. Further studies with transmission electron microscopy are needed to better understand the physiological function of these external structures. PMID- 11784931 TI - [List of the type species of Ceratopogonidae (Diptera, Nematocera) deposited in the Entomological Collection of Instituto Oswaldo Cruz, Rio de Janeiro, Brazil]. AB - A list of all type specimens of the Family Ceratopogonidae, present in the Entomological Collection of Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil is presented. This list includes the genera Bahiahelea, Culicoides, Dasyhelea, Downeshelea, Forcipomyia, Leptoconops, Mallochohelea, Monohelea, Neobezzia, Palpomyia and Sphaerohelea. PMID- 11784932 TI - Ixodes (Haemixodes) longiscutatum Boero (new status) and I. (H.) uruguayensis Kohls & Clifford, a new synonym of I. (H.) longiscutatum (Acari: Ixodidae). AB - Females of Ixodes (Haemixodes) uruguayensis Kohls & Clifford, 1967, a species whose adults were unknown until the present, were obtained in the laboratory from engorged nymphs collected on rodents (Scapteromys tumidus and Oxymycterus nasutus) in the counties of Maldonado and San Jose, Uruguay. Morphological characters of these females were identical to those given in the description of the female of Ixodes longiscutatum Boero, 1944. I. uruguayensis is, thus, relegated to a junior subjective synonym of I. longiscutatum. However, because of the unique morphological characters of the immature stages, the validity of the subgenus Haemixodes Kohls & Clifford, 1967 is not questioned. Therefore, the new status of Ixodes (Haemixodes) uruguayensis Kohls & Clifford, 1967 is Ixodes (Haemixodes) longiscutatum Boero, 1944. PMID- 11784933 TI - Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. AB - The western region of the Brazilian Amazon Basin has long been shown to be a highly endemic area for hepatitis B and hepatitis D viruses. Data concerning the prevalence of hepatitis C and E viruses in this region are still scarce. In this study we investigated the presence of hepatitis A, B, C, D and E viruses infection in communities that live along the Purus and Acre rivers in the states of Acre and Amazonas within the Amazon Basin. A total of 349 blood samples were collected and tested for hepatitis A-E serological markers (antibodies and/or antigens) using commercial enzyme linked immunosorbent assays. Anti-HCV positive sera were further assayed by an immunoblot. HBsAg positive sera were subtyped by immunodifusion. The overall prevalence for hepatitis A, B, C, and E were 93.7%, 66.1%, 1.7%, and 4%, respectively. A very high prevalence of delta hepatitis (66.6%) was found among HBsAg positive subjects. Hepatitis A, B and D viruses were shown to be largely disseminated in this population, while hepatitis C and E viruses infection presented low prevalence rates in this region. The analysis of risk factors for HBV infection demonstrated that transmission was closely associated with sexual activity. PMID- 11784934 TI - Detection of Mycobacterium leprae DNA by polymerase chain reaction in the blood of individuals, eight years after completion of anti-leprosy therapy. AB - Thirty eight patients with indeterminate leprosy (HI), at least 4 to 6 years after discharge from multibacillary (MB) or paucibacillary (PB) schemes of anti leprosy multidrug therapy (MDT), were submitted to traditional diagnostic procedures for leprosy and to polymerase chain reaction (PCR) analysis of different clinical samples for detection of Mycobacterium leprae DNA. No significant difference was observed for any of the parameters analyzed between PB or MB schemes of treatment and no indications were found for more efficient outcome of HI using the MB scheme. Remarkably, 18 (54.5%) of the individuals were PCR positive in at least one of the samples: positivity of PCR was highest in blood samples and four individuals were PCR positive in blood and some other sample. Upon comparison of PCR results with clinical and histopathological parameters, no correlation was found between PCR-positivity and eventual relapse. This is the first report on detection of M. leprae DNA in PB patients, more than half a decade after completion of MDT, suggesting that live bacilli are present and circulating much longer than expected, although reinfection of the individuals can not be excluded. Overall, we feel that because of the high sensitivity of the assay, extreme care should be taken about association of PCR results, efficacy of treatment and disease status. PMID- 11784935 TI - Antibodies anti-Chlamydia pneumoniae and anti-Mycoplasma pneumoniae in patients with negative serology for hantavirus. Retrospective study. AB - The seroprevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae in hantavirus seronegative patients, who had symptoms and signs compatible with pneumonia was established. For this purpose we used the indirect fluorescent antibody test. Titers > or = 1:16 for C. pneumoniae and M. pneumoniae were found in 8.6% and 17.1% of the serum, respectively, showing evidence of recent or current infection. PMID- 11784936 TI - Inhibition of the polymerase chain reaction by sputum samples from tuberculosis patients after processing using a silica-guanidiniumthiocyanate DNA isolation procedure. AB - With the objective to evaluate PCR-mediated detection of Mycobacterium tuberculosis DNA as a diagnostic procedure for diagnosis of tuberculosis in individuals attending ambulatory services in Primary Health Units of the City Tuberculosis Program in Rio de Janeiro, Brazil, their sputum samples were collected and treated with a DNA extraction procedure using silica guanidiniumthiocyanate. This procedure has been described to be highly efficient for extraction of different kind of nucleic acids from bacteria and clinical samples. Upon comparing PCR results with the number of acid-fast bacilli, no direct relation was observed between the number of bacilli present in the sample and PCR positivity. Part of the processed samples was therefore spiked with pure DNA of M. tuberculosis and inhibition of the PCR reaction was verified in 22 out of 36 (61%) of the samples, demonstrating that the extraction procedure as originally described should not be used for PCR analysis of sputum samples. PMID- 11784937 TI - Ultrastructural features of the midgut epithelium of females Lutzomyia intermedia (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae). AB - A morphological study of the midgut of Lutzomyia intermedia, the primary vector of cutaneous leishmaniasis, in southeast Brazil, was conducted by light, scanning and transmission electron microscopy. The midgut is formed by a layer of epithelium of columnar cells on a non-cellular basal lamina, under which there is a musculature, which consists of circular and longitudinal muscular fibers. A tracheolar network is observed surrounding and penetrating in the musculature. Females were examined 12, 24, 48, 72 h and 5 days following a blood meal and were analyzed comparatively by transmission electron microscopy with starved females. In starved females, the epithelium of both the anterior and posterior sections of the midgut present whorl shaped rough endoplasmic reticulum. The posterior section does not present well-developed cellular structures such as mitochondria. Observations performed at 12, 24, 48 and 72 h after the blood meal showed morphological changes in the cellular structures in this section, and the presence of the peritrophic matrix up to 48 h after the blood meal. Digestion is almost complete and a few residues are detected in the lumen 72 h after blood feeding. Finally, on the 5th day after the blood meal all cellular structures present the original feature resembling that seen in starved sand flies. Morphometric data confirmed the morphological observations. Mitochondria, nuclei and microvilli of midgut epithelial cells are different in starved and blood fed females. The mitochondria present a similar profile in the epithelium of both the anterior and posterior section of the midgut, with higher dimension in starved females. The cell microvilli in the posterior section of the midgut of starved females are twice the size of those that had taken a blood meal. We concluded that there are changes in the midgut cellular structures of L. intermedia during the digestion of blood, which are in agreement with those described for other hematophagous diptera. PMID- 11784938 TI - Spermatogenesis and spermiogenesis in Didymocystis wedli Ariola, 1902 (Didymozoidae, Digenea). AB - The ultrastructure of the male reproductive system of Didymocystis wedli was studied for the first time, demonstrating spermiogenesis and spermatogenesis at different cell stages. The spermatozoa morphology was compared with that of other Digenea species. It was observed that the different cells of the spermatogenesis process follow the classic pattern reported for the majority of the parasitic platyhelminthes. During spermiogenesis, rootlet fibers, electrondense bodies and median cytoplasmic process were not observed. The mature spermatozoa of D. wedli were filiform, presenting nucleus, mitochondrion and two 9+1 axonemes, with a biflagellate distal extremity. PMID- 11784939 TI - Aminotransferases activity in the hemolymph of Bradybaena similaris (Gastropoda, Xanthonychidae) under starvation. AB - Aminotransferases (GOT and GPT) activities in the hemolymph of Bradybaena similaris under experimental condition of starvation were studied. At the 10th day of starvation, GOT activity was 416.6% higher than that observed in the fed snails, being reduced and ranging values near to that shown by the control group onwards. GPT activity only varied significantly at the day-30 of starvation. The results were discussed. PMID- 11784940 TI - Occurence of larval Culicidae (Diptera) in water retained in Aquascypha hydrophora (Fungus: Stereaceae) in Central Amazonia, Brazil. AB - The community structure of insects, especially mosquito larvae, in water held in the fungus Aquascypha hydrophora (Berk.) Reid (Stereaceae) is reported. The study was done in the Adolpho Ducke Forest Reserve, 26 km east of Manaus, AM, Brazil, from September 1998 through November 1999. The most abundant entomofauna were immature Culicidae (n = 121) 91.7%, followed by adult Dytiscidae (n = 3) 2.3%, immature Chironomidae (n = 5) 3.8% and immature Tipulidae (n = 3) 2.3%. Culicidae associated with A. hydrophora comprised species of the subfamilies Anophelinae and Culicinae. PMID- 11784941 TI - Infestation of Rhynchopsyllus pulex (Siphonaptera: Tungidae) on Molossus molossus (Chiroptera) in Southeastern Brazil. AB - The infestation of Rhynchopsyllus pulex on the bat Molossus molossus was observed using mist-nets opened between constructions in the Primatological Center, in Guapimirim, State of Rio de Janeiro, Brazil. PMID- 11784942 TI - Mites (Acari: Laelapidae) associated with sigmodontinae rodents in Entre Rios Province, Argentina. AB - The richness, diversity, abundance and prevalence of mite species associated with sigmodontine rodents of different species in Entre Rios province, Argentina are studied. Five of the six species of mites were reported for the first time in the study area. The richness and diversity of mites was higher on Oligoryzomys flavescens and O. delticola than on Akodon azarae. Androlaelaps rotundus was dominant and exhibited higher values of mean abundance and prevalence on A. azarae, Mysolaelaps microspinosus on O. flavescens and Gigantolaelaps mattogrossensis on O. delticola. PMID- 11784943 TI - Blood parasites in some birds from eastern plains of Colombia. AB - A total of 315 birds representing 75 species (23 families) from Villavicencio and San Miguel (Meta, Colombia) were examined for haematozoa. Fifty birds (15.9%) harbored blood parasites. Microfilariae were the most common haematozoans encountered, followed by species of the genera Haemoproteus, Plasmodium and Trypanosoma. This survey included 15 new host-parasite records and 8 species of birds that were examined for haematozoa for the first time. The prevalence registered in this research was similar to others recorded in the Neotropical region, but in sharp contrast with the prevalence of blood parasites in other major land masses. PMID- 11784944 TI - House dust mites in Brazil--an annotated bibliography. AB - House dust mites have been reported to be the most important allergen in human dwellings. Several articles had already shown the presence of different mite species at homes in Brazil, being Pyroglyphidae, Glycyphagidae and Cheyletidae the most important families found. This paper is an annotated bibliography that will lead to a better knowledge of house dust mite fauna in Brazil. PMID- 11784945 TI - [Epidemiology of hemorrhagic cerebrovascular disease in the central region of Cuba]. AB - INTRODUCTION: Cerebrovascular diseases are the third most important cause of death in Cuba. Among the programmes given priority by the Cuban Ministry of Public Health and the World Health Organization (WHO), hemorrhagic disorders are the most lethal . OBJECTIVE: To determine the behaviour of hemorrhagic cerebrovascular disease in the central region of Cuba. PATIENTS AND METHODS: . An exploratory, descriptive, retrospective study in which 1,401 clinical histories were reviewed. The variables being investigated were then processed using the computer data processor EPINFO 6.0 to determine the mean, standard deviation and chi squared. RESULTS: An annual incidence rate of 84.03 per 100,000 persons was seen for hemorrhagic cerebrovascular disease; 54.16 and 29.86 per 100,000 persons respectively for intracerebral hemorrhage and subarachnoid hemorrhage; and total mortality of 68.95%. The disorder was associated with possible meteorological factors and the highest percentage was due to intracerebral hemorrhage with 64.45%. Arterial hypertension was the most intensely studied risk marker (p< 0.01). Most cases were elderly (p< 0.001). Surgical treatment was given to 81 patients with subarachnoid hemorrhage, with a predominance of malformations of the middle and anterior cerebral arteries. Treatment was based on depletion using Manitol and calcium antagonists. A considerable number of patients required mechanical ventilation and vaso active drug support. Most were attended in Intermediate Polyvalent Treatment Units and the main complication was sepsis. CONCLUSIONS: There is a high mortality from hemorrhagic cerebrovascular disease in the central region of Cuba, and once the diagnosis has been made the prognosis is usually poor. The patients included in the programme of attention for subarachnoid haemorrhage showed promising results. PMID- 11784946 TI - [Tectal tumours in paediatrics. A review of eight patients]. AB - INTRODUCTION: Tumours of the tectal region form, within the group of gliomas of the brain stem, a sub group with better prognosis which require a different therapeutic strategy. OBJECTIVES: A retrospective review of tectal tumours in children to find the most suitable therapeutic approach and the prognosis to be expected. PATIENTS AND METHODS: We reviewed 8 paediatric patients who, during the past 11 years, had developed tectal tumours diagnosed by means of neuro imaging techniques. We evaluated their clinical features and especially their clinico radiological progress. RESULTS: The average age at the time of diagnosis was 10 years. All cases presented with the clinical features of raised intracranial pressure secondary to obstruction of the aqueduct of Sylvius. MR was the key to visualization of the tectal lesion in all cases but one, which had already been shown on CT. The initial and only treatment given was a ventricular shunt. The average clinico radiological follow up in our series was 4 years, with good progress in all cases so that no other therapeutic measures were required. MR follow up showed that the tumours were stable in all cases but one, which had increased slightly in size but without parallel clinical signs. CONCLUSION: In most cases tectal tumours in children follow a benign course. A ventricular shunt is usually the only treatment necessary. However, close clinical and radiological follow up should be carried out to rule out growth of the tumour which make other treatment also necessary. MR is the method of choice for initial evaluation and follow up of these tumours. PMID- 11784947 TI - [Madrid adaptation of the Wisconsin card sorting test: a comparative study of internal consistency]. AB - INTRODUCTION: WCST (Wisconsin Card Sorting Test) is still a widely used neuropsychological test for evaluation of disorders of the frontal lobes. Recent studies have cast doubt on the validity of WCST as a marker for frontal dysfunction. OBJECTIVES: We present a simplified version of WCST specially designed to evaluate the capacity to change the criteria for attention. Our objectives were to examine the difference in standards and in internal consistency between our adaptation and the conventional WCST. SUBJECTS AND METHODS: The two tests were applied to a group of 60 young persons with no cerebral disorders. The principal components of both tests were analysed for determine their internal structure. RESULTS: We found statistically significant differences between the scores of Spanish persons and the standard data for WCST. Analysis of the main components showed a solution of two components in the conventional WCST and a solution of three components in our adaptation. CONCLUSIONS: The American rating system underestimated the level of performance in the Spanish sample. Analysis of the internal consistency showed the excessively redundant and simple factorial structure of the conventional WCST. Our adaptation was shown to have a richer internal structure, with the order of error scores more in accord with the type of cognitive process involved. These advantages may be attributed to more exact analysis of non perseverant errors, subclassified as efficient errors (i.e. linked to comparison of hypotheses) and random errors (i.e. linked to loss of criteria for attention). PMID- 11784949 TI - [A shortened form of the Spanish Boston naming test: a useful tool for the diagnosis of Alzheimer's disease]. AB - INTRODUCTION: The Boston Naming Test (BNT) is the most frequently used test of confrontation naming. Due to its length, several abbreviated forms have been proposed. OBJECTIVE: The aim of the study was to develop a short form for the Spanish version of the BNT that could detect early semantic changes in Alzheimer s disease (AD). PATIENTS AND METHODS: One hundred and three patients with diagnosis of probable AD (NINCDS ADRDA criteria), with GDS< 5 and 143 normal subjects, matched for age and education, were studied. Subjects with <4 years of education were excluded. No subject had any history of neurological of psychiatric disorders or alcohol abuse. All participants underwent a comprehensive neuropsychological assessment which included the 60 item Spanish version of the BNT. The sensibility and specificity of each item and demographic effect s variability were calculated (ANOVA). Those 12 figures with the highest sensibility and specificity which showed no significant educational or age variation were administered to all participants. The Spearman correlation coefficient was used. RESULTS: Mean score for the control group was 11 (standard deviation: 1.16). No significant effects for age (r= 0.14574) or education (r= 0.101293) were found. The sensibility and specificity for correctly diagnosing AD was 85% and 94% respectively, similar to the longest version. CONCLUSION: This 12 item version of the BNT can be a useful instrument for a rapid screening of AD, as it is as sensible and specific as the 60 item version, and it is not influenced by age or education. PMID- 11784948 TI - [An ultrastructural study of the temporal lobe and peripheral blood in schizophrenic patients]. AB - INTRODUCTION: In spite of the human, social and economic impact of schizophrenia and to be considered a disease of organic origin by several evidences, there are relatively few studies about this disease using electron microscopic techniques. PATIENTS AND METHODS: For 23 years we made studies about the viral hypothesis of schizophrenia by means of this technique. We studied limbic structure samples from young adult s dead schizophrenic patients, from fetuses of schizophrenic mothers and from chicken embryos experimentally inoculated with cerebrospinal fluid from schizophrenic patients. In the last ten years we have performed studies of blood and cerebrospinal fluid samples from young schizophrenic patients. We have found some alterations with the same characteristic to those observed in the central nervous system, which are compatible with: a) the viral hypothesis and b) with herpes simplex hominis type I virus, when immuno electronmicroscopic techniques were made. RESULTS AND CONCLUSION: The results obtained in this work can constitute a new element favoring the possible viral etiology of this disease. PMID- 11784950 TI - [Clinical and neuropathological study of two brothers with Cockayne syndrome]. AB - INTRODUCTION: Cockayne syndrome (CS) is a rare autosomal recessive disease which is characterized by physical and mental retardation, progressive neurological disfunction, photosensitivity and other cutaneous features. Usually they present ophthalmologic abnormalities as well as other heterogenous clinical, radiological and pathologic features as leucodistrophy and calcifications in central nervous system and segmental demyelination in peripheral nervous system. CLINICAL CASES: Two brothers, sons of healthy unrelated parents, are presented. The first patient was referred at 8 months of age because of psychomotor retardation and the second one at 5 months old because of a cataract. At the age of 2 years both presented a complex clinical picture with photosensitivity, growth and mental retardation, peripheral neuropathy, neurosensorial deafness, and cerebral atrophy and calcifications in neuroimaging diagnosis tests. In the following years the older brother presented signs of renal failure, cataracts and retinopathy, and died at 9 years old because of a respiratory infection. The neuropathologic study showed a discrete neuronal loss and diffuse demyelination with calcium deposits in cerebral white matter and basal ganglia. Today the second patient is 8 years old and shows a clinical course similar to that of his brother. CONCLUSIONS: Clinical, radiologic and pathologic features in our patients support the diagnosis of CS type II. PMID- 11784951 TI - [Brain SPECT in a case of Wernicke Korsakoff syndrome]. AB - INTRODUCTION AND CLINICAL CASE: In this article we report a 44 year old male with chronic alcoholism as antecedent and Wernicke Korsakoff s syndrome, studied with brain CT, MR and SPECT. In this work we review the different conclusion obtained with different studies and in different stages of the chronic alcoholism disease. CONCLUSIONS: Although several authors have described impaired frontal blood flow in the Wernicke Korsakoff s syndrome, in our case the parietal, temporal and occipital cortex were the most affected. PMID- 11784953 TI - [Channelopathies in neurology]. AB - INTRODUCTION: The main function of ionic channels are the conduction, recognition and selection of specific ions. They open and close in respond answer to electrical, mechanical and chemical stimulus, acting in the excitation or transmission of diverse tissues. DEVELOPMENT: The clinical and molecular manifestations of channelophathies are varied and use to shown up in continuous or paroxystic ways. Alteration of Ca channels cause muscle dysfunction periodic paralysis with or without potassium changes, myasthenia or myasthenic disorders, like Lambert Eaton syndrome, amyotrophic lateral sclerosis, Central Core disease, malignant hyperthermia. Cl and Na channels alterations produce myotonic diseases: Thomsen, Becker and paramyothonies, potassium sensible paralysis, fluctuant congenital myotonic, Andersen s syndrome. Channelopathies also produce various episodic ataxia type 1, type 2, spinocerebellar 6 and familial hemiplegic migraine. Abnormal paroxystic movements are present as channelophaties: episodic nocturnal dystonia, paroxystic dyskinesia. In some families are associates abnormal episodic movements and epilepsy. Several epileptic syndromes are also related with channels dysfunction: frontal lobe nocturnal epilepsy, choreoatetosis epilepsy, benign neonatal convulsions, generalized epilepsy with febrile convulsions plus. CONCLUSIONS: Voltage gated channels dysfunction are related to diseases with episodic phenomena or permanent conditions on muscle or neuronal tissues, with clinical and genetic heterogenous manifestations. PMID- 11784952 TI - [Structure and function of the cerebellum]. AB - INTRODUCTION: The cerebellum is a neural structure, of a crystalline like organization, present in all vertebrates. Its progressive growth from fishes to mammals, and particularly in primates, takes place following the repetition of a primitive cellular plan and connectivity. DEVELOPMENT: The cerebellum is organized in folia located one behind the other in the rostrocaudal axis, and placed transversally on the brain stem. The cerebellar cortex has five types of neuron: Purkinje, stellate, basket, Golgi and granule cells. Apart from granule cells, the other cell types are inhibitory in nature. Afferent fibers to the cerebellar cortex are of two types (mossy and climbing) and carry information from somatosensory, vestibular, acoustic and visual origins, as well as from the cerebral cortex and other brain stem and spinal motor centers. The only neural output from the cerebellar cortex is represented by Purkinje axons that synapse on the underlying deep nuclei. Cerebellar nuclei send their axons towards many brain stem centers and, by thalamic relay nuclei, act on different cortical areas. Functionally, the cerebellum seems to be organized in small modules, similar in structure, but different in the origin and end of their afferent and efferent fibers. The cerebellum is involved in the coordination or integration of motor and cognitive processes. CONCLUSION: Although cerebellar lesion does not produce severe motor paralysis, loss of sensory inputs or definite deficits in cognitive functions, its certainly affects motor performance and specific perceptive and cognitive phenomena. PMID- 11784954 TI - [Participation of interleukin 1 and interleukin 6 in the aetiopathogenesis of Alzheimer's disease]. AB - OBJECTIVES: In this study we review the major concepts related to the immunological aspects which have currently been shown to be, perhaps, one of the basic factors of the so called neuroimmune cascade which characterizes Alzheimer s disease (AD). We emphasise the mechanisms causing these alterations, their repercussions and implications in this disease. DEVELOPMENT: There is a close relationship between the nervous, immune and endocrine systems, due to the presence of molecules such as the interleukins which permit this connection, for example: the IL 1 and IL 6 are involved in the immunological events which occur in AD, in which it has been suggested that the cell damage and neurodegeneration which occurs may be due to a neuroimmune reaction together with inflammatory mechanisms. The World Health Organization (WHO) has estimated that in the coming years, the population affected will reach a total of 423 million persons aged over 65, including a prevalence of 13.9% of persons aged between 70 and 89 years with AD. CONCLUSIONS: It is necessary to have clear, precise, reliable knowledge of the neuroimmune mechanisms involved in AD, if we take into account that the quantitative determination of interleukins may be a key to the overall evaluation of patients with AD. It may also be a useful tool for the follow up of patients treated by a method of neuro restoration. This is useful when classifying each patient and will lead to a better quality of life. PMID- 11784957 TI - [A new reibergram for evaluation of the intrathecal synthesis of IgG3]. PMID- 11784958 TI - [Parkinsonism, cognitive disorder and cerebral cryptococcosis]. PMID- 11784959 TI - [Morphometric evolution of some diameters of the caudal part of the human neural tube during the embryonic period]. PMID- 11784961 TI - [The prevalence of idiopathic Parkinson's disease]. PMID- 11784962 TI - [Cerebral vasoreactivity and functional response in stroke: a study with functional MR]. AB - INTRODUCTION: Lacunar infarcts are usually associated with anatomical and possibly functional changes in the walls of small blood vessels (penetrating arteries). The functional effect varies and is accompanied by cerebral adaptive/reorganizational changes. BOLD contrast, originated in the microvasculature (especially with ultra high magnetic fields) depends, in the end, on haemodynamic changes and is useful for exploring patterns of cerebral activation using fMR. OBJECTIVES: To compare the temporal behaviour of the BOLD signal and the distribution of activation between a group of patients with no functional sequelae following a stroke and a control group, by using fMR at 3T. RESULTS: The stroke group showed a smaller number of voxels activated, but this was not statistically significant. The patterns of activation, size of the sensor motor area (SM or ASM) and index of laterality were similar in both groups. In SM the BOLD response was 85% slower (p< 0.01) and 25% less (not statistically significant). CONCLUSIONS: We found no differences in the patterns of activation of the two groups. This may be explained by the minimal lesions of the stroke group, which were insufficient to produce reorganizational/adaptive changes or by the great variety of responses. The temporal response of the BOLD response was different in the stroke group, probably as a result of the alteration in the haemodynamic response in relation to the underlying processes which damage the functional properties of the vascular wall. This difference in the BOLD response should be interpreted with caution, and borne in mind when interpreting activation in persons with vascular pathology. Further studies are necessary for better understanding of its significance. PMID- 11784963 TI - [Clinical characteristics of migraine in childhood]. AB - INTRODUCTION: The clinical presentation and progression of childhood migraine has still not been clearly defined. However, major advances in prognosis and treatment would follow this. OBJECTIVE: To trace the clinical features and course of childhood migraine. PATIENTS AND METHODS: A prospective study, lasting 10 years, in a population of 284 children with migraine, seen at two hospitals. The data obtained were analysed using techniques of statistical significance and logistic regression. RESULTS: In 24.3% headaches started before the age of 6 years, and in 57% at between 6 and 10 years of age. In 77.5% of the patients there was a family history of migraine, this figure rose to 82.6% in the children whose headaches started before the age of 6 years. Characteristics such as duration, site and accompanying factors differed from those seen in adults. There was spontaneous improvement in 88.3%, who did not require prophylactic medication. CONCLUSIONS: Childhood migraine has some characteristics which distinguish it from adult migraine. This should be noted in classification. Most children with migraine have mild headaches which do not require prophylaxis. A genetic factor appears to play an important rol in phenotype expression of the disorder. PMID- 11784964 TI - [Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly. A randomized controlled trial]. AB - INTRODUCTION: 40 to 50% of elderly with hip fracture present delirium. The morbimortality increase in patients whose presented delirium. OBJECTIVE: To study the use of citicoline (CDP choline) in the prevention of delirium in elderly under hip fracture surgery. PATIENTS AND METHODS: A randomized control trial. The patients with hip fracture without dementia or an other organic brain illness. The medication were administered 24 hours before and during 4 days after surgery. The doses was 1.2 g/day. The primary outcome measure was percentage of patients with delirium measured with Abbreviated Mental Test (AMT) and Confusion Assessment Method (CAM). The Mini Mental State (MMS) was used before and 4 days after surgery. All treatment comparation was considered statistically significant at p< 0.05 calculating chi square and Wilcoxon test. RESULTS: The sample size was 81 patients (46 placebo and 35 citicoline). The mean age was 79.45 for tested group and 79.97 for placebo. There was no statistically significant difference between groups with respect to ASA class of anesthesia. The incidence of delirium was 17.39% in placebo and 11.76% in citicoline group (p= 0.6). CAM and AMT at 1, 2, 3, 4 days post surgery was not significant in placebo and citicoline group (p= 0.8 and p= 0.34). CONCLUSION: In the present study the citicoline did not prevent or reduce the incidence of delirium in hip fracture surgery in elderly. PMID- 11784965 TI - [Working memory and complex activities of everyday life in the initial stages of Alzheimer's disease]. AB - INTRODUCTION: Evaluation of the working memory (WM) permits analysis of the degree of anterograde amnesia and fixation deficit present in patients with Alzheimer s disease (AD). Complex activities of everyday life (AEL) are also affected early. There is a close relation between the degree of cognitive deterioration and loss of functional competence in AEL. OBJECTIVE: To analyze the degree of memory loss and performance in carrying out complex AEL in patients with AD and mild cognitive disorder. PATIENTS AND METHODS: Evaluation of functional disorder, using Pfeffer s functional activity questionnaire (FAQ), and cognitive evaluation, using the WM examination protocol in a group of 36 patients. RESULTS: In the total MT (4.2+/-5.7) there were significant differences between patients with age associated memory impairment (AAMI) (11+/-7) and possible EA (3.2+/-4.6) and between AAMI and probable AD (2.8+/-4.8). The functional evaluation of the AEL (FAQ) gave a mean of 8.5+/-7.1. There were significant differences between probable AD (11+/-8) and possible EA (6+/-4) with the group AAMI 1+/-1.8. There was significant correlation between FAQ and total WM ( 0.70, p= 0.0001). It was found that patients with high FAQ scores had lower total WM scores. CONCLUSION: FAQ and WM have high correlation and are useful instruments for the evaluation of patients with cognitive deterioration at the initial stages. PMID- 11784966 TI - [Transient neurological deficit secondary to a leptomeningeal cyst in an adult patient]. AB - INTRODUCTION: An uncommon complication of fractures of the skull in infancy is a leptomeningeal cyst, which is also known as a growing skull fracture. A post traumatic leptomeningeal cyst may occur in adults, but is much rarer and may be attributed to a fracture of the skull which occurred in childhood. This complication is caused by a tear in the dura mater, through which pulsation of the cerebro spinal fluid forces the arachnoid layer to herniate. The commonest clinical finding is a soft tissue swelling or tumour appearing on the head. CLINICAL CASE: We report the case of a 47 year old man, with a past history of a head injury in childhood. He presented complaining of loss of sensation in the right arm and deviation of the mouth, from which he recovered within an hour. Neuro imaging studies showed irregular destruction of the right temporal bone and hypodensity of the underlying brain tissue. Surgical operation and histological study of the bone removed showed that it was a leptomeningeal cyst, associated with a cerebral infarct at the site of an old skull fracture. CONCLUSIONS: A post traumatic leptomeningeal cyst in an adult patient is caused by a tear in the dura mater caused by a skull fracture during childhood. It may be associated with a cerebral infarct. It may present with only transient focal neurological symptoms. PMID- 11784967 TI - [Crossed apraxia secondary to a right parietal infarct]. AB - INTRODUCTION: Crossed apraxia is an unusual alteration in praxic function due to a cerebral lesion which is contralateral to that which would be expected. We report a case of crossed apraxia due to a right parietal lesion in a left handed patient who had been obliged to be right handed. We discuss the peculiar neuropsychological profile and possible relation of this to left handedness. CLINICAL CASE: A 75 year old man, left handed but obliged to use the right hand, suffered an acute episode of alteration in the management of utensils (lids, taps, medicine containers), although he maintained his usual social behaviour and orientation. On neurosomatic examination no focal deficits were observed. On MMST he scored 29/30, on the Edinburgh questionnaire he scored 35 (left handed dominance). On a Barcelona PIENC battery his scores were in the pathological range for subtests on understanding orders, carrying out symbolic gestures and imitating gestures, in perceiving super imposed images and visual memory. MRI showed a right parietal laminar infarct. CONCLUSIONS: The patient showed clear bilateral ideo motor apraxia, which could not be justified/explained by visuo spatial agnosia secondary to a right parietal ischaemic lesion. It is usually considered that ideatory and ideomotor apraxias are due to left hemisphere lesions, whilst contsructive apraxia and apraxia related to dress are due to right hemisphere lesions. In this case, there was ideomotor apraxia secondary to a right parietal lesion, that is to say a crossed ideomotor apraxia, without crossing of other neuropsychological functions. This supports the theory of independence of hemisphere dominance for different cognitive functions. The frustrated left handedness of the patient might be related to the greater probability of unusual hemisphere dominance for ideomotor praxis function in this particular case. PMID- 11784969 TI - [Cluster headache in a 3 year old child]. AB - INTRODUCTION: Cluster headache is a rare disorder in childhood. We identified, in the literature, 64 cases of cluster headache starting at or before 18 years (only 17 of them began before 10 years old). All patients met the criteria of the International Headache Society. Russell et al demonstrated recently that the cluster headache is an inherited disorder in some families. They conclude that the gene is present in 3 to 4% of males and 7 to 10% of females with cluster headache and that it has an autossomal dominant transmission. CLINICAL CASE: The authors report the clinical case of a five year old child with cluster headache starting at three years. This paper reviews the differential diagnosis and the treatment of cluster headache. PMID- 11784968 TI - [Myxoma of the mitral valve with embolization of the posterior circulation. A case report and review of the literature]. AB - INTRODUCTION: Although cardiac tumours are infrequent, over half are myxomas. Most are situated in the cavities of the heart and exceptionally on the valves. Embolism towards the arteries of the anterior circulation of the central nervous system is the commonest neurological finding, but rarely involves the posterior circulation. CLINICAL CASE: A 79 year old woman who one year before admission had had a right hemiparesia of the face and body, from which she had made a complete recovery. Three months later she had a sudden onset of unsteady gait which was deviated towards the right and vertigo. She attended our institution where magnetic resonance (MR) studies showed that there were infarcts in the territory of the right anterior and posterior inferior cerebellar arteries. Four months later she had a further episode of unsteady gait, vertigo and right hemiparesia of face and body for which she was admitted to hospital. On physical examination there was dysmetry, dysdiadokokinesia and involvement of the third cranial nerve. Further MR studies showed the previous lesions and also a new ischaemic lesion of the mesencephalum. A transoesophagic echocardiogram showed a tumour of approximately 18 x 20 mm, implanted in the mitral valve. Study of the resected tumour showed it to be a myxoma. Six months later the patient was asymptomatic and had not relapsed. CONCLUSION: Although the association of vascular events of the posterior circulation with myxomas of the mitral valve is rare, its clinical importance cannot be overlooked. PMID- 11784970 TI - [Hypophonia in lacunar stroke]. AB - INTRODUCTION: Hypophonia has been defined as a reduction in speech volume. It is an uncommon finding in acute stroke, mainly related to multiple deep infarcts. CLINICAL CASE: An 82 year old hypertensive woman was admitted to our hospital presenting acute right sided weakness and low speech volume. She was hypophonic and unable to yell. Language was fluent without paraphasic errors. A diffusion weighted magnetic resonance showed a small hyperintense lesion in the left corona radiata. No other lesions were detected. CONCLUSIONS: Although, the precise anatomic area involved in the brain has not been clearly precised yet, hypophonia may be also due to isolated lacunar affecting the penetrating arteries in the corona radiata. Further studies are necessary to better understand the nature and the prognosis of this phenomenon. PMID- 11784971 TI - [Post traumatic partial seizures]. AB - INTRODUCTION: Post traumatic epilepsy represents 4% of the prevalence of the disorder and is one of the sequelas which is most difficult to prevent. Risk factors have been described to predict the appearance of seizures. CLINICAL CASE: A seven year old boy with a severe head injury was admitted to the Intensive Care Unit. On neuroimaging studies there were multiple foci of contusion, mainly in the left hemisphere, and blood in the III and IV ventricles and frontal horn of the left lateral ventricle. The patient had severe sequelae of head injury with a right spastic hemiplegia and hemiparesia with hypertony of the left side, together with complete blindness of both eyes due to bilateral atrophy of the optic nerve. Serial EEG were done, in which a recording showed alternating periods of hypervoltage grapho elements superimposed on a trace of very low voltage, with continuous activity of low voltage and low frequency. There were no grapho elements with acute morphology. However, the patient had a first partial seizure a year and a half after his head injury. On the EEG an epileptogenic focus was identified in the left hemisphere. Within two years of his head injury he had seven seizures. He had not received prophylactic antiepileptic treatment after the head injury. CONCLUSIONS: We report a case of epilepsy secondary to a head injury, in which the first seizure occurred one and a half years after injury. In view of the risk factors, we discuss whether prophylactic anti epileptic treatment might have been beneficial. PMID- 11784972 TI - [Ionic channels and second messenger alterations in Alzheimer's disease. Relevance of studies in nonneuronal cells]. AB - INTRODUCTION: Numerous observations indicate that, while the predominant clinical expression arises from brain pathology, Alzheimer s disease (AD) has systemic expression at the cellular and molecular levels. Although these alterations seem to be inconsequential outside the central nervous system, their parallel expression in the brain could be considered a plausible pathophysiological model and explain part of the clinical manifestations; in particular those related to memory loss. DEVELOPMENT: Recent research has provided experimental evidence of a direct or indirect linkage between alteration in ion channels, PKC, calcium homeostasis and amyloid processing in peripheral tissues. Some evidence also indicates similar phenomena in the brain, attesting to the relevance of the changes in non CNS cells. CONCLUSION: Considering the difficulties of using post mortem material to study dynamic and/or early event in mostly end stage, disease ridden tissues, peripheral cells such as fibroblasts offer a model to study cellular aspects of AD pathophysiology. PMID- 11784973 TI - [Cerebrovascular disease in the tropics]. AB - OBJECTIVES: To review the clinical manifestations, diagnosis, and therapy of diseases causing cerebrovascular disease (CVD) in the tropics. DEVELOPMENT: Most prevalent conditions causing CVD in the tropics include: sickle cell disease, Takayasu s arteritis, cysticercosis, infective endocarditis, Chagas disease, viral hemorrhagic fevers, gnathostomiasis, leptospirosis, snake bites, cerebral malaria, puerperal venous thrombosis, and tuberculosis. These conditions may cause cerebral infarcts or hemorrhages, and in most instances are related to either vascular damage secondary to angiitis or hemorrhagic diathesis with bleeding in other organs. In some patients, the severity of the neurological picture makes impossible to identify an specific stroke syndrome and cerebrovascular complications are only recognized on neuroimaging studies or autopsy. CONCLUSIONS: There is a group of tropical infectious and non infectious diseases that may cause cerebral infarcts or hemorrhages. Prompt diagnosis and therapy are needed to reduce the severity or brain damage and to avoid recurrent strokes. PMID- 11784975 TI - [Type 1 neurofibromatosis: the experience of a hospital in Porto, Portugal]. PMID- 11784976 TI - [Metastasis to the orbit from breast cancer simulating bilateral orbitary pseudotumours]. PMID- 11784977 TI - [Association between chronic inflammatory demyelinating neuropathy predominantly of the arms and penphigus vulgaris]. PMID- 11784978 TI - [Guillain-Barre syndrome associated with gastric adenocarcinoma. Paraneoplastic origin or coincidence?]. PMID- 11784979 TI - [Cuban epidemic optic myeloneuropathy: discrepancies regarding its possibly viral aetiology]. PMID- 11784980 TI - [Iatrogenic neuropathy of the XI cranial nerve or accessory nerve]. PMID- 11784981 TI - [Prognostic value of electrocorticography in temporal lobe epilepsy: patterns of relationing mesial and neocortical activity]. AB - INTRODUCTION: Electrocorticography (ECoG) monitoring in temporal lobe epilepsy (TLE) has been employed since the 40 s as a means to delineate surgical removal especially in lesional epilepsy, to reduce resection size and decrease cognitive sequelae (memory, naming). However in recent years, ECoG has been claimed to lack indications and prognostic value in cases of non lesional TLE. On the grounds of the pathophysiological relationship between mesial structures and neocortex (through propagation pathways) we have suggested a classification of ECoG activity patterns regarding the activities simultaneously recorded in mesial and neocortical grids. PATIENTS AND METHODS: Two experienced neurophysiologists (over 200 ECoG performed) have independently reviewed the recordings (including video EEG monitoring with foramen ovale electrodes) of 33 consecutive (28 non-lesional) TLE patients with the major criterion of a leading activity in mesial or neocortical areas, and related the results to the clinical course. RESULTS: As a result we identified five patterns: I. Pure mesial; II. Mesial with neocortial related activity; III. Non-related mesial and neocortical activities; IV. Neocortical preponderance (although some mesial unrelated discharges may be seen), and V. Neocortical origin. In all 33, a tailored, ECpG-guided two-steps resection was performed. Surgical success significantly (c2 test) associated with patterns I, II and IV. Pattern V precluded a good outcome. CONCLUSIONS: ECoG reflects the state of pathological involvement of neocortex and mesial structures. An expertise approach, although brief in time (20-30 min), may either lead to preservation of relevant tissue (patterns I, II) and to establish a prognosis on the grounds of the initial epileptogenic activity. PMID- 11784982 TI - [Intrathecal oligoclonal and polyspecific immune response in multiple sclerosis]. AB - INTRODUCTION: The intrathecal response of IgG, is the most frequent neuropathological sign in multiple sclerosis (MS) patients beside the detection of oligoclonal IgG bands in cerebrospinal fluid. At the same time the observation of an intrathecal antibody synthesis (antibody index> 1.4) against neurotropic viruses like measles, rubella, varicella zoster or herpes simple shows a higher frequency in MS than any other chronic disease (MRZH reaction). We report the intrathecal, polyspecific and oligoclonal immune response in patients with definitive MS. PATIENTS AND METHODS: CSF and serum were tested for Albumin, IgG, IgM and IgA by standard immunochemical nephelometry assay while virus specific antibodies in CSF and serum samples were evaluated by ELISA and calculated as antibody index. RESULTS: Oligoclonal IgG by, isoelectric focusing was detectable in all patients. A differential pattern of combined antibody index against neurotropic virus was observed. The largest frequency of a single species in the oligoclonal immune response was for measles antibodies, while the antibody response was found as a combination with increased rubella antibody index and VZ antibody index, respectively. CONCLUSION: Our results although preliminary for our country, enrich the criteria about that MRZH reaction provide a major neuroimmunological support to MS diagnosis. PMID- 11784983 TI - [Evaluation of maturity in drawing in childhood. I. Evaluation and validation of a graphomotor test in a population of normal children]. AB - INTRODUCTION: The tests for measuring the ability of a child for copy a drawing take no less than 15 minutes and require a direct attention to the patient. This makes them almost impossible to use in the neurological or paediatric consultation. OBJECTIVE: In this report a new test of drawing copy, the grafomotor test, is presented. It is composed by 8 easy figures: diamond, stair, cross, flower, clock, house, cube and bicycle and the score method is simple. The progressive maturation of drawing in childhood and the reliability and validity of the test are studied. PATIENTS AND METHODS: Two studies were done: a) 210 children aged 5 12 (all the children belonging to two classes of every age ) of a medium high socioeconomic level primary school made the test, remade it again after 24 hours, and them were scored blindly by a neuropediatrician and a school psychologist. b) 133 children (5 11 year old) of a paediatric consultation of a medium low socioeconomic level. Every child who wanted draw the test. RESULTS AND CONCLUSIONS: 1. The score system proposed is easy and takes less than 1 minute to do. The perfect test get a score of 0, and the worst possible a score of 20; 2. Result show high reliability: interobserver Pearson s correlation coefficient r> 0.92, and reliability Cronbach alpha coefficient= 0.97; test retest reliability r> 0,91 and alpha= 0,95. 3. It is a valid tool to measure visuomotor maturation in childhood. Average scores are different at every age until 11 years. 4. There is no difference in scores between children of the two socioeconomic levels studied. 5. The test is easy, and fast to do and to score. It takes 5 10 minutes and can be passed in the same neurological or paediatric consultation, while talking with the parents. Results depend on mental or drawing level, not on the socioeconomic status. 6. GT is, therefore, proposed as another tool to add to the neurological clinical examination. PMID- 11784984 TI - [Diagnostic tests in myasthenia gravis. Creation of a standard for diagnosis using a method of consensus]. AB - INTRODUCTION: Nowadays the best test for the diagnosis of myasthenia gravis (MG) is the single fiber electromyography (SFEMG). Due to the cost of the test it has not become routine in most part of the hospitals to confirm the diagnosis of MG. OBJECTIVE: To identify an acceptable gold standard for hospitals which do not have access to SFEMG, but have access to some other classical test through the use of a consensus methodology. SUBJECTS AND METHODS: The study was realized in three stages. The first two stages were done through a prolective survey and the third stage through a Delfos methodology. During the first stage 59 general neurologist were interviewed, applying an instrument in which they were asked which were the best test and the best group of tests to diagnose MG without using the SFEMG. During a second stage, a second collection instrument was applied to 15 experts in motoneuron diseases to identify the best isolated test and the best test scheme with and without using the SFEMG in four frequent clinical situations in clinical practice (typical clinical case of generalized MG, patient with ocular myasthenia, patient with generalized MG of medium and low probability). Finally four flowcharts were created of the four analyzed clinical situations and were approved through a Delfos methodology with 8 neurologist motoneuron disease. RESULTS: We identified an acceptable gold standard for hospitals which do not have access to SFEMG through the use of a consensus methodology. We have also completed four diagnostic flowcharts about the most frequent clinical situations that we have faced in the ordinary practice. CONCLUSIONS: We have found a series of important results for the diagnosis of MG available to general physicians, internists and neurologist that do not have all the test for the diagnosis of MG. PMID- 11784985 TI - [The importance of the identification of the spaces of Virchow-Robin. A report of four cases]. AB - OBJECTIVE: To emphasize the importance of recognizing the Virchow Robin spaces as normal anatomic structures on magnetic resonance (MR). CLINICAL CASES: Presentation of four patients seen in the Pediatric Neurology Department in La Paz Hospital. They consulted for different reasons, having been studied by MR to help identify their pathology. RESULTS: The MR showed cystic structures which correspond to dilated Virchow Robin spaces in several zones of the cerebral white matter. CONCLUSIONS: Although dilated Virchow Robin spaces have been associated with various pathologies, they constitute normal anatomic structures, which consists of perivascular spaces surrounding the cerebral perforating arteries, which should always be kept in mind when visualizing cystic structures in the cerebral white matter and basal ganglia, circular or elongated, following the path of the perforating blood vessels, and which have the same intensity of cerebrospinal fluid on T1 sequences as on T2 on MR, especially if they are bilateral and multiple. PMID- 11784986 TI - [Mobile carotid plaque]. AB - INTRODUCTION: In the literature only seven cases have been published describing a mobile carotid plaque, and lack of precise description makes it difficult to differentiate these lesions from mobile thrombotic lesions. The natural history of these lesions is not known and their treatment is controversial, although there is a tendency to choose the type of treatment to be given according to the embologenic potential of the lesion. CLINICAL CASES: We report two cases with mobile carotid plaques. In both cases diagnosis was made on ultrasound Doppler. The first patient had neurological symptoms and a mobile plaque associated with stenosis of over 70%. Surgical treatment was indicated. The second patient had no neurological symptoms. On ultrasound Doppler studies there was a fragment of mobile plaque in the common carotid artery, in the region of the carotid sinus with stenosis of 30 50%. Distal to this zone, in the bulb of the internal carotid artery there was stenosis of >70%. In this case medical treatment was given in view of deterioration in the patient s general state. Both patients improved. CONCLUSIONS: Including our second case, three patients with mobile carotid plaques (neurologically asymptomatic) have now been reported to have made good progress with medical treatment. Until there is more data regarding the natural history of these lesions, they should not be considered to be in themselves sufficient reason for carrying out carotid endarterectomy. The possibility of indicating surgical treatment depends on the degree of carotid stenosis. PMID- 11784987 TI - [Intracranial tumors simulating transient ischemic attacks]. AB - INTRODUCTION: Occasionally intracranial tumors present a clinical picture similar to that seen with transient ischemic attacks (TIA). The mechanism for this is not clear. The differential diagnosis of these two disorders is important since their treatment is quite different. CLINICAL CASES: Two men and two women aged between 53 and 72 years of age, with no known cardiovascular risk factors, complained of one or several episodes of neurological deficit (hemisensitive deficits, transient blindness and isolated aphasia), lasting between 3 minutes and 6 hours. Neuroimaging investigations (CT and MR) showed images compatible with space occupying lesions localized to the convexity (parietal, frontotemporal and frontoparietal) and in one case at the edge of the sphenoid bone. Three patients were operated on. The lesions were confirmed as tumors (two cases of meningiomas and one of glioblastoma). Symptoms did not recur after a mean follow up period of nine months. Various mechanisms have been suggested to explain this phenomenon: vascular compression due to pressure from the mass, changes in intracranial pressure, vascular steal phenomenon, negative focal seizures, Leao s cortical depression and others. The absence of risk factors which would justify a vascular cause, the correlation between localization of the tumour and the clinical signs, and the disappearance of symptoms following surgery would seem to support the hypothesis that in our cases the symptoms observed were due to intracranial space occupying lesions. CONCLUSION: The presence of an intracranial tumour should be ruled out by using neuroradiological investigations in patients complaining of transient episodes of neurological deficits. PMID- 11784988 TI - [The evolution of the structure of the neocortex in mammals: a new theory of cytoarchitecture]. AB - INTRODUCTION: The evolution of the structural organization of the mammalian neocortex can only be appreciated studying its ontogenetic development. DEVELOPMENT: We studied its evolution in embryos of different mammals (hamster, mouse, rat, cat and man) using the Golgi method. Development of the neocortex starts with the establishment of a primordial plexiform layer (PPL) in the telencephalus. This PPL represents a primitive cortical organization which is shared by amphibians, reptiles and mammals. From the PPL derived: the layer 1 with its elements including: the Cajal Retzius cells (CR) and primitive afferent fibres of a possibly origin in mesencephalic nuclei and the elements the interstitial cells and afferent fibres of the subplaca. The formation of the PPL is a prerequisite for the subsequent formation of the cortical plate (CP) from which the remaining layers of the neocortex derived. The ascending neuronal migration, the morphology of pyramidal neurons and the inside outside arrangement of neurons within the CP are evolutionary processes controlled by the CR cells. These neurons secrete a glycoprotein reelin which attracts the migrating neurons toward the first layer. All migrating neuroblasts, guided by the radial glia, must reach layer 1, establish contacts with the CR cells, develop an apical dendrite and become pyramidal cells. Without losing either their original contact with layer 1 or their cortical level, each neuron has to elongate its apical dendrite to accommodate the arrival of subsequent neurons, such that all develop a common initial pyramidal morphology. Older neurons have longer apical dendrites and deeper cortical level than the newer ones. The subsequent morphological and functional maturation of the CP neurons also follows an ascending progression and is under thalamic control. Two basic types of neurons develop in the neocortex following its ascending stratification. Some neurons maintain their original contact with the first layer to become the pyramidal cells. Others lose their original contact with layer 1 and become stellate interneurons. These neurons are free to develop specific size, spatial morphology and synaptic endings. The CP is a mammalian innovation and represents a biologically open and stratified nucleus which adds, during mammalian evolution, new pyramidal cell strata to those already present. CONCLUSIONS: Based on the above observations, we propose a new cytoarchitectural theory and nomenclature for the structural evolution of the mammalian neocortex. The theory emphasizes the ascending structural and functional stratification of the mammalian neocortex and the increase in the number of pyramidal cell strata reflecting the motor needs of each species. PMID- 11784989 TI - [Ischemia of the vertebrobasilar territory: mechanisms and practical considerations]. AB - OBJECTIVE: We first review historic, anatomic, and epidemiological aspects involving the vertebrobasilar territory ischemia. We describe the development of ideas regarding the stroke mechanisms and treatment in the posterior circulation. Key authors and their contributions are also mentioned. DEVELOPMENT: Several new diagnostic and therapeutic strategies have emerged during the last few decades in cerebrovascular disease. The comprehension of the ischemic stroke in the posterior circulation is more difficult than carotid circulation. Thus, vertebrobasilar stroke represents a microcosm. Several mechanisms may explain the ischemic process (large artery disease, penetrating vessel disease, cardioembolism, unusual causes of stroke, and combined or undetermined causes). One of the most common is large artery atherosclerosis. Transient ischemic attacks, usually stereotyped, may be the clue for the earliest recognition. Correct diagnosis may improve the chance of effective therapy. Some practical considerations may help to identify the underlying cause of the stroke. CONCLUSIONS: The prognosis in patients with vertebrobasilar ischemia depends on: a) the mechanism of the stroke, b) site of the vessel occlusion, c) thrombus propagation, d) collateral circulation, e) hemodynamic (hypertension, cardiac output, etc.), and hemorreologic factors (viscosity, hypercoagulable state, etc.), f) neurologic status, g) time to treatment. The accurate the diagnosis of the mechanism, the better the prognosis. PMID- 11784991 TI - [Unilateral paresia of the third cranial nerve in a child with benign intracranial hypertension]. PMID- 11784992 TI - [Epilepsy and dementia due to Lewy bodies]. PMID- 11784993 TI - [Traumatic dissection of the middle cerebral artery. A case report]. PMID- 11784994 TI - [Physiological ossification of the falx cerebri. Findings on magnetic resonance]. PMID- 11784995 TI - [There is controversy as to whether invasive or non invasive diagnosis of carotid artery disease is preferable: here it is considered from a different approach]. PMID- 11784997 TI - [Intercellular communication in the astrocyte culture as a measure of therapeutic efficacy in multiple sclerosis treated by interferon]. AB - INTRODUCTION: Measurement of therapeutic efficacy in multiple sclerosis depends on the clinical and magnetic resonance findings on follow up. There are no biological markers. Measurement of interleukins and other markers of inflammation has not proved useful in the follow up of these patients. The response of astrocytes to mediators of inflammation gives rise to modification in their capacity for intercellular communication. OBJECTIVE: To find whether culture of astrocytes in serum from patients with multiple sclerosis at different clinical stages and on different treatments gives rise to modification in intercellular communication. PATIENTS AND METHODS: Astrocytes were cultured in serum from three patients with an untreated acute clinical episode of multiple sclerosis, and the results compared with those obtained after serum culture when the patients had been treated with interferon for a year. RESULTS. In astrocyte culture using serum from patients with an acute episode of multiple sclerosis, but not on treatment with interferon, there was a statistically significant reduction in intercellular communication as compared to astrocytes cultured with serum from these same patients treated with interferon for one year (*p< 0.05; **p< 0.01). CONCLUSION: Measurement of the modifications in intercellular communication on astrocyte culture may be used as a marker for inflammatory activity in the serum of patients with multiple sclerosis, and therefore as an index of therapeutic efficacy. PMID- 11784998 TI - [Type 2 spinocerebellar ataxia: acceptance of prenatal diagnosis in descendents at risk]. AB - INTRODUCTION: Type 2 spinocerebellar ataxia is a hereditary degenerative disorder of the nervous system. Advances in molecular genetics have made it possible to carry out presymptomatic and prenatal studies. A programme to define the strategies and principles for doing this has been devised. OBJECTIVE: To find the level of acceptance of prenatal diagnosis in couples at risk, and to determine the effect of different variables on this acceptance. PATIENTS AND METHODS: We made a descriptive type study of a series of cases. The study group included 226 persons. Forty of these were couples of descendents and the remainder were asymptomatic descendents. We applied a questionnaire, after prior information as to the aims of the study and obtaining the consent of the participants. RESULTS: Regarding acceptance of prenatal diagnosis by couples of descendents, we found that most (77.5%) accepted this and only 2.5% did not. Prenatal diagnosis was accepted by 67.74% of the descendents themselves. CONCLUSIONS: In general there was a high level of acceptance. 159 of the 226 questioned claimed that they would like to have more children and 98.7% of these accepted the test, whilst only 0.01% refused it. The main reasons given were the hope of having healthy children and that the disease would not occur in future generations. PMID- 11784999 TI - [Complications of treatment of epilepsy by a ketogenic diet]. AB - INTRODUCTION: It was originally claimed that the ketogenic diet (KC) caused no major adverse effects. Few studies have been done to analyze the side effects and complications of the KC. OBJECTIVES: To analyze the side effects and complications seen in a group of patients on KC compared with those described in the international literature. PATIENTS AND METHODS: We made a prospective evaluation of 22 patients aged between one and nineteen years, over an average period of 25 months. All had some type of refractory epilepsy and had been included in a group treated following classical KC guidelines. RESULTS: The side effects and complications during admission were delay in onset of the ketotic state (10.5%), intolerance of the rapid onset of ketosis (21%), hypoglycaemia (47.37%), refusal to drink fluids (15.79%), lack of appetite (15.79%), and nausea and vomiting (26.31%). During treatment the serum cholesterol rose in 64.7% of the children, 40.91% were constipated, 31.82% had periods of anorexia, symptomatic metabolic acidosis occurred during intercurrent infections in 9.09%, renal calculi in 9.09%, carnitine insufficiency in 9.09% and severe complications which led to hospital admission in 21.05%. CONCLUSIONS: Our group of patients had no more side effects or complications than those described in the literature. KC may lead to complications, especially when strict guidelines for control and follow up are not used. However, they are usually easy to correct if detected early. PMID- 11785000 TI - [Clinical diagnostic of brain death and transcranial Doppler, looking for middle cerebral arteries and intracranial vertebral arteries. Agreement with scintigraphic techniques]. AB - INTRODUCTION: The Real Ordinance 2070/1999 meant an important modification in the legislation, when including transcranial Doppler (TCD) in explorations to confirm the clinical diagnosis of brain death (BD). Habitually for their employment in the diagnosis of BD, we look for blood flow signal from the middle cerebral arteries (MCA) and the basilar artery (BA). OBJECTIVES: To check the effectiveness of the TCD like test of BD, looking for both middle cerebral arteries (MCA) and both intracranial vertebral arteries (VA), instead of the BA, and taking as Gold Standard cerebral scintigraphic techniques. PATIENTS AND METHODS: . We present 25 patients diagnosed clinically with BD; on these TCD was carried out to confirm BD. Later on we proceeded to carry out cerebral scintigraphic techniques in all these cases. As statistical tool the test of c2 is used with confidence interval of 95%. RESULTS: In 24 of the 25 cases, the TCD was effective in confirming the diagnosis of BD. In the remaining patient, a false positive result was obtained, since the TCD didn't reveal flow in the infratentorial compartment, as contrary to the cerebral scintigraphic techniques which showed the presence of residual flow at this level; this residual flow disappeared in 36 hours. This patient was hemodynamically unstable during TCD exploration. CONCLUSIONS: In our results the TCD obtains a reliability of 100% when confirming the absence of blood flow in the supratentorial compartment; nevertheless the false positive result obtained at the infratentorial level, warns us to be cautious in accepting the flow from the VA as a test of absence of flow at the infratentorial compartment, especially in those patients with hemodynamic instability. PMID- 11785001 TI - [Cost effectiveness of treatment with triptanes in Spain]. AB - INTRODUCTION: Migraine is a very common disorder and frequent cause of consultation of the neurologist. The triptanes have been a great advance in the treatment of migraine attacks. At present it is the treatment of choice in severe attacks of migraine, but it is more expensive than the other drugs used for this. Taking into account the greater efficacy and the saving in direct and indirect costs which may be due to treatment with triptanes, its use may not only be effective but also efficient. OBJECTIVE: To analyze the cost effectiveness of the triptanes sold in Spain (sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan). MATERIAL AND METHODS: We analyzed the efficacy, therapeutic gain and number of different triptanes needed for treatment. We evaluated the cost of multiplying the result of the number needing treatment by the price of each unit of the drug. The results are expressed in pesetas and in euros. RESULTS: Rizatriptan gave the best results and was the cheapest triptan, followed by sumatriptan and zolmitriptan. When criteria of efficacy were used, naratriptan was the most expensive triptan, in spite of being the cheapest per unit. CONCLUSIONS: In chronic, recurrent disorders such as migraine, when the cost of treatment using triptans is assessed, one has not only to evaluate the cost per unit but also to introduce other parameters such as the efficacy of the drug, which is one of the most important. PMID- 11785002 TI - [Perioperative antibiotic prophylaxis in neurological surgery]. AB - INTRODUCTION: Perioperative antibiotic prophylaxis is a current topic of interest. However, in neurosurgery there are no controlled studies or full reports to support its use. We have also observed that there is little consistency in the use of antibiotics in this type of surgery. This method has been used in other specialities, reducing the risk of postoperative sepsis. We therefore consider that it may be used in neurosurgery, bearing in mind certain specific aspects. OBJECTIVES: To find the postoperative sepsis in a consecutive group of patients in whom prophylaxis was used for neurosurgical operations. PATIENTS AND METHODS: We made a prospective, observational, descriptive study of 100 patients who needed neurosurgical operations and were given antimicrobial agents to prevent sepsis. The relation between intracranial and extracranial surgery, the use or not of these agents and the occurrence or not of sepsis was observed. The method was applied using the classification of the National Research Council of the USA. RESULTS. In spinal surgery, the method was used most and no difference was found with or without the use of antibiotics in cervical spinal surgery, with regard to the occurrence of sepsis. Exogenous factors played an important part in the development of sepsis unrelated to the surgical technique. CONCLUSIONS: The complications related to surgery were minimal. However, general complications occurred more frequently. PMID- 11785003 TI - [Aggressive behaviour in dementia. RAGE scale, validation of the version in Spanish]. AB - INTRODUCTION: Aggressive behaviours are frequent in the different phases of dementia s evolution. These not only constitute a major problem for the families and the caring staff, but cause fatigue and bur out among them. As these behaviours cannot be predicted or understood, the carers experience very complex and anguishing situations. To avoid subjective factors, Patel and Hope designed and validated a scale named RAGE that can be easily used. OBJECTIVE. Adaptation and validation of the RAGE Scale into Spanish. PATIENTS AND METHODS: The scale has been translated, and then retrotranslated to guarantee the semantic equivalence. Afterwards it has been tested on a group of 60 patients (n= 60). All these patients followed the dementia criteria in DSM-IV and their behaviours were considered as relevantly aggressive by their carers. RESULTS: The total score reliability got an r= 0.93 Spearman coefficient. The internal consistency was determined by Cronbach s alpha (0.90) and the valiability test-retest, analysed by Cohen s kappa, obtained a range from 0.57 to 0.85. CONCLUSIONS: All these elements show similar data in comparison to the original scale validation and therefore this version can be considered adequate for Spanish speaking patients within the Spanish culture. PMID- 11785004 TI - [Exogenous factors in the aetiology of multiple sclerosis in Cuba. A study of cases and controls]. AB - INTRODUCTION: Descriptive epidemiological studies indicate that the prevalence of multiple sclerosis (MS) in Cuba is in the mid range of risk. It is not known what exogenous factors may be related to the aetiology of MS. OBJECTIVE: To study the exogenous factors possibly related to the aetiology of MS in the central provinces of Cuba. PATIENTS AND METHODS: We studied all the patients with definite clinical MS (Poser et al) with positive MR who came from the provinces of Cienfuegos, Villa Clara and Sancti Spiritus. The protocol was approved by the Medical Ethics Committees of each of the three institutions and reviewed by two international authorities on the subject. Each of the patients (cases) and one member of their family (control), after written consent, when they fulfilled the criteria for inclusion in the study, were personally interviewed by trained persons and the questionnaire for studying cases and controls of Boiko et al was completed. The questionnaire had been adapted for use in Cuba. The main data obtained were: demographic data, history of occupation and residence, personal medical history, exposure to possibly toxic substances, diet and nutrition, contact with animals and life style. For measurement of risk we used the risk of the results of the crossed products odds ratio (OR) with its confidence interval (CI), always insisting on precision of 95%. RESULTS: High educational level (OR= 2.293; 95% CI= 0.9 5.4), two or more children (OR= 2.84; 95% CI= 1.22 6.59), four or more pregnancies (OR= 3.60; 95% CI= 0.69 18.7), three or more deliveries (OR= 1.939, 95% CI= 0.44 8.4); previous measles infection (OR= 2.042; 95% CI= 0.76 5.47), a history of migraine (OR= 2.538; 95% CI= 0.81 7.94); stress (OR= 3.768; 95% CI= 1.64 8.62) and insomnia (OR= 2.95; 95% CI= 1.14 7.14) were the factors related to MS. CONCLUSIONS: This study confirmed the existence of exogenous factors in the aetiology of patients with clinically defined MS and positive MR findings who lived in the provinces studied in Cuba. The exogenous factors found in this population of patients with MS were: high educational level, two or more children, four or more pregnancies, three or more deliveries, previous measles, a history of migraine, stress and insomnia. PMID- 11785005 TI - [Evaluation of maturity in drawing in childhood. II. Development and validation of a graphomotor test in a child with neuropsychiatric disability]. AB - INTRODUCTION: In a previous report the graphomotor test (GT) has been validated as a useful, simple, fast, valid and reliable tool for knowing the drawing maturation in childhood. OBJECTIVE: In this report the data of validity and reliability of the graphomotor test in patients with diverse mental levels and diverse neurological and psychiatric disorders are presented. PATIENTS AND METHODS: Two different studies were done: A) In a prospective study all patients (n= 349, aged 5-40) of a neurology and psychiatric department completed the test, and repeated it after 15-30 minutes. 276 of them were also studied with Wechsler test (WPPSI-R, WISC-R or WAIS-R) and in other 53 cases the mental level was known. The tests were scored blindly and separately by a neuropediatrician an a clinical psychologist. B) The results of all the cases (n= 1,001) studied with this test during the clinical consultation with their parents were analyzed. RESULTS AND CONCLUSIONS: 1. The GT is a reliable tool for measuring the visuomotor level of children with diverse neuropsychiatric disorders and mental levels above IQ 50: Cronbach's alpha coefficient= 0,98 (test-retest) and= 0,98 (between different observers), and Pearson's r correlations> 0,92 (p< 0,001). The repetition of the test does not change the score. 2. The GT is a valid tool for measuring drawing maturation and the nonverbal intelligence in childhood. Pearson's correlations with verbal, performance and total Wechsler test IQ (VIQ, PIQ and TIQ) were significant (p< 0,01), the best of them were with the PIQ and with the spatial capability factor of Wechsler test (r= -0.58 to -0,72, p<0,001). 3. GT is a very sensitive screening test of the cognitive non-verbal level of patients, with a high negative predictive value (0,97), and this allows to select the cases to study by means of deeper neuropsychological tests. 4. It is a simple, fast and easy test to be done. It can be assessed in the same neurological or pediatric consultation, while talking with the parents. 5. The results are related with the mental level and with the age more than with the type of disorder. 6. GT is, therefore, proposed as another tool to add to the neurologic clinical examination. PMID- 11785006 TI - [Microcephaly, bilateral corneal opacity and congenital lobar holoprosencephaly with subsequent development of a rhabdomyosarcoma in a patient exposed to prenatal radiation]. AB - INTRODUCTION: Most congenital malformations of which the cause is known are due to genetic or multifactorial causes or are secondary to a teratogen. Many congenital malformations are of unknown origin. However, the association of different malformations allows us to define the moment in which the noxous agent affected embryonic or foetal development. CLINICAL CASE: We present the case of a baby born after 40 weeks gestation, who had been exposed to ionising radiation before birth. Prenatal echography showed microcephaly and the karyotype was normal. The newborn baby had corneal opacities, microcephaly and complex encephalic malformations. The corneal opacity together with congenital glaucoma constitute Peters syndrome which leads to blindness, and is treated by trabeculectomy and bilateral corneal transplants. The microcephaly and lobar holoprosencephaly with agenesis of the corpus callosum led to reduced psychomotor development, hypertonia and epilepsy with an electroencephalogram recording of hemihypsarrythmia which was unsuccessfully treated with valproate and vigabatrine. At the age of 21 months the patient developed an embryonic rhabdomyosarcoma of the base of the tongue. He died with systemic infection whilst being treated with chemotherapy. CONCLUSIONS: The association of the malformations described has not previously been reported in the international data bases. Although it was not possible to prove that prenatal exposure to radiation caused the clinical condition described, the possibility of teratogenesis and carcinogenesis following such exposure means that pregnant women or those who may be pregnant should not be in places where radiodiagnosis is carried out. PMID- 11785007 TI - [Cerebral hematoma caused by mucormycosis]. AB - INTRODUCTION: Invasion of the central nervous system by mucormycosis is rare. It is mainly seen in diabetic ketoacidosis, immunosensitive or severely debilitated patients and in cases of hematological neoplasias. We describe a case of cerebral hemorrhage with documented evidence of invasion of the cerebral vessels by mucormycosis, in a patient with a gastric adenocarcinoma. CLINICAL CASE: A 38 year old woman complained of the sudden onset of headache and disorder of vision which progressed rapidly to coma. Computerized tomography showed the presence of a parieto occipital hematoma. The patient died six hours later. She had had an operation for gastric carcinoma eight months previously. Anatomopathological study of the brain showed invasion of the arterial wall by mucormycosis. CONCLUSION: Solid tumors may lead to cerebral hemorrhage caused by mucormycosis. PMID- 11785008 TI - [Isolated posterior cord syndrome in Lyme s disease: a clinico neurophysiological study]. AB - INTRODUCTION: Lyme disease, caused by spirochete Borrelia burgdorferi, is a multisystemic infectious disorder with prominent neurologic involvement, affecting both the peripheral and the central nervous system. Meningitis, cranial neuritis and radiculoneuritis are the usual manifestations in the acute phase, and peripheral neuropathy in the chronic phase. Other less common manifestations have been also described. Here we report one case of Lyme disease confirmed by PCR, with a previously undescribed neurological manifestation, and the neurophysiological studies performed before and after treatment. CLINICAL CASE: Our patient showed a chronic and progressive clinical picture consisting of instability on walking and distal paresthesia of lower limbs, suggestive of posterior column disfunction. The neurophysiological exam performed prior to treatment with ceftriaxone revealed bilateral absence of lower limbs somatosensory evoked potentials (SEPs), without alterations in the distal nervous conduction or in upper limbs SEPs. The exam performed after treatment revealed a partial recovery of lower limb SEP with presence of an evoked response in SEP of left lower limb, coincident with a transitory clinical improvement of paresthesia in the same extremity. CONCLUSIONS: Our findings reveal that posterior column disfunction can be a neurological manifestation of Lyme disease. Furthermore the neurophysiological study shows that this manifestation is partially reversible following treatment. Our study emphasize the importance of the neurophysiological tests for the diagnosis and follow up of neurological manifestations of Lyme disease. PMID- 11785009 TI - [Chin tremor in a peruvian family]. AB - INTRODUCTION: Chin tremor is an uncommon hereditary autosomic dominant disorder, characterized by involuntary, episodic, and repetitive movements involving chin muscles, stimulated by stress. It was first described by Massaro in 1894 like geniospasmo . The most reported cases are from Europeans or Americans families. CLINICAL CASE: A 53 years old man with chin tremor since childhood. CONCLUSIONS: We report the first Peruvian family with chin tremor without European nor American ascendancy with six affected members in four generations. PMID- 11785010 TI - [Eosinophilic myositis in a 9 year old boy]. AB - INTRODUCTION: Eosinophil infiltration of skeletal muscle is rare, but often no etiological factor can be identified and these are isolated eosinophilic myositis. They may be associated with parasite infections or drugs, or be features of rare systemic disorders of hypereosinophilia, such as the myalgia eosinophilia syndrome and the idiopathic hypereosinophilic syndrome. The eosinophilic myopathies should be distinguished from the commoner inflammatory myopathies such as polymyositis and dermatomyositis. CLINICAL CASE: A nine year old boy with slight motor clumsiness but normal psychomotor development and neurological findings. Laboratory findings showed slightly raised serum transaminases (SGOT 271, SGPT 157 UI/L), CPK 7517 UI/L and eosinophilia (707/mL). Investigations for myoglobin cysticercosis, trichinosis, hydatidosis and toxicariasis were negative. No parasites were found in the faeces. The gammaglobulins were normal. Anti smooth muscle, antinuclear and anti KLM antibodies were negative. Cardiological studies were normal. His father, mother and two siblings had normal results of laboratory tests. Muscle biopsy showed inflammatory myopathy with abundant eosinophils, no evidence of parasites, no alteration of membrane proteins: dystrophin, sarcoglycan and merosine. Two years later he remains asymptomatic, maintains raised muscle enzyme levels in all tests with figures for CPK between 3,065 and 9,616UI/L, and eosinophilia ranging between 634 and 1,026/mL. Corticosteroid treatment was tried but no response obtained. CONCLUSION: We consider this to be a case of eosinophilic polymyositis which gives rise to many questions regarding etiopathogenesis, management and prognosis. PMID- 11785011 TI - [Surgical treatment of spondylodiscitis in ankylosing spondylitis. Two cases report]. AB - INTRODUCTION: Spondylodiscitis in ankylosing spondylitis has a prevalence of 5%. Mechanical and inflammatory factors are involved in its pathogenesis. Neurosurgical operation is required when neurological complications or vertebral instability occur. Surgery is complicated by the increased fragility of the vertebral column, advanced stage of the disease in many patients, and serious pulmonary complications. CLINICAL CASES: We report two patients who had had ankylosing spondylitis for over 20 years. Both presented complaining of symptoms for several months with lumbar pain and signs of spinal cord lesions. There were signs of discitis and destruction of the adjacent vertebral bodies at T11 T12 and T12 L1 on imaging investigations of the first and second patient respectively. In both cases an anterior approach was used for discectomay and resection of the adjacent vertebral plates. Then an autologous rib graft was done, and anterolateral fixation with plate and screws to the adjacent vertebral bodies. The patients condition improved. Their pain and previous clinical neurological disorder had disappeared by 5 and 1 year later. DISCUSSION AND CONCLUSIONS: The prevalence of patients operated on for spondylodiscitis in the context of ankylosing spondylitis is not known. Dorsolumbar pain with inflammatory characteristics of recent onset in patients with chronic ankylosing spondylitis should lead to suspicion of spondylodiscitis. Although it may be related to previous trauma, discitis is the fundamental mechanism. MR is the most sensitive imaging technique. There may be marked osteoporosis and stenosis of the vertebral canal together with marked ossification of all the paraspinal ligaments. This hinders the approach to the vertebral bodies and their subsequent fixation. Decompression of the vertebral canal using an anterior approach (thoracotomy or thoraco phreno laparotomy) and anterior spinal fixation is the treatment of choice in cases with neurological involvement or involvement of the anterior and medial columns of Denis. PMID- 11785012 TI - [Presenilins in the genesis of Alzheimer s disease]. AB - INTRODUCTION: With their discovery in 1995, presenilins were put forward as molecules of unknown function but central to the aetiology of Alzheimer s disease. DEVELOPMENT: The fact that point and splice mutations lead to an increase in the amount of Ab peptide produced by the cells, provided further support for the amyloid theory about the origin of the disease and, on the other hand, placed these molecules in the central part of this theory. Different groups showed that these proteins had also roles in several cellular pathways, among those, the notch pathway is one of the most important, as it is with the interaction among presenilin 1 and b catenin. Recently, several works have suggested that presenilins are molecules involved in the processing of APP by being an integral part of the protein complex that process the precursor to produce the amyloid peptide. CONCLUSION: In this paper, I will give an overview of some of the most recent work developed towards the identification of presenilin function and its involvement in Alzheimer s disease. PMID- 11785013 TI - [Human brain activity in response to emotional visual stimuli: open issues and recent data]. AB - INTRODUCTION: The traditional circumplex model on the structure of emotion postulates that this process is organized in two basic dimensions: valence (positive negative) and activation (relaxing activating). This model assumes that the valence activates a single evaluative system. With regard to cerebral activity, two ideas are derived from this assumption: 1) a single set of mechanisms and neural circuits becomes activated in response to both positive and negative events, 2) the faculty of response to adverse and pleasant responses (i.e., latency and intensity with which the neural structures involved can respond) is potentially balanced. DEVELOPMENT: We describe the debates on these two issues and, subsequently, the current data regarding them are also described. These data indicate that, in response to aversive stimuli (often noxious), neural systems characterized by their ability to produce an immediate response are preferentially activated. On the other hand, pleasant stimuli (which lead to an approaching behavior towards the stimulus) preferentially activate systems associated with more intense and precise information processing. This is a slower but longer lasting type of activity. CONCLUSION: The data suggest that there are separate mechanisms for the evaluation and preparation of a response according to whether the stimulus is negative or positive. PMID- 11785015 TI - [In memory of the personality of Juan Rof Carballo]. PMID- 11785014 TI - [Intracranial ependymomas]. AB - INTRODUCTION: Ependymomas are tumours derived from ependymal cells, found lining the cerebral ventricles and central canal of spinal cord. Intracranial ependymomas account for 2 6% of all neoplasms of the central nervous system and at least half present in the first two decades of life. DEVELOPMENT: We review the epidemiological, clinical, neuropathological details, neuroradiological aspects and treatment of intracranial ependymomas. CONCLUSIONS: Ependymomas of the posterior fossa predominate in children, while supratentorial tumours are more common in adults. This analysis of the literature further highlight that total tumour removal is the treatment of choice for intracranial ependymomas. Postoperative survival was predominantly dependent on the histological grade of malignancy, the extension of surgery and the age of the patient. PMID- 11785016 TI - [Attention disorders in a sample of complex partial epileptic children]. PMID- 11785017 TI - [Contralateral approaches in the surgical treatment of bilateral cerebral aneurysms]. PMID- 11785018 TI - [Absence of the corpus callosum, colpocephaly and schizophrenia]. PMID- 11785019 TI - [Encephalopathy retarded by carbon monoxide]. PMID- 11785020 TI - [Response to recombinant human erythropoietin of anemia secondary to pressure ulcers in a patient with multiple sclerosis]. PMID- 11785021 TI - [Corticobasal degeneration. Description of a consanguineous case]. PMID- 11785022 TI - [Neurorehabilitation in multiple sclerosis]. PMID- 11785023 TI - [Type 2 spinocerebellar ataxia: an experience in psychological rehabilitation]. AB - INTRODUCTION: Psychological rehabilitation in patients with neurodegenerative disorders helps to improve their quality of life and provide the most suitable approach to their disease. There are no records of this type of treatment being used in type 11 spinocerebellar ataxia. OBJECTIVES: To evaluate the efficacy of group therapy within the framework of psychological rehabilitation and determine the most favored psychological function markers. PATIENTS AND METHODS: This study is a quasi experimental study of 24 patients with type 2 spinocerebellar ataxia rehabilitated in the CIRAH (Cuba). The procedure involved psychological assessment before and after the strategy for intervention, which consisted of 15 sessions of group therapy. RESULTS: The pathological levels of anxiety were reduced in 50.1% of the cases, and 31.4% of the patients with depression improved. The self assessment markers of a taking step forward were happiness and worry level. The disorder affected all aspects of the life of the patients studied, particularly their interests, family, self esteem and work. CONCLUSIONS: It is possible to improve the attitude of the patient to his disease and his psychological function by means of group therapy during the process of psychological rehabilitation of patients with type 2 spinocerebellar ataxia. PMID- 11785024 TI - [Can sural nerve biopsy be used to orientate the treatment of chronic inflammatory demyelinating polyneuropathy?]. AB - INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired neuropathy characterized by demyelination of the peripheral nerves and roots. The course of the illness is progressively chronic or of relapses and remissions. Biopsy of the sural nerve is not essential for diagnosis. It is therefore not necessary to carry it out on all occasions, but probably permits a more rational approach to treatment. OBJECTIVE: To show whether biopsy of the sural nerve is useful for orientation of the treatment required in cases of CIDP. PATIENTS AND METHODS: We studied a total of 16 patients admitted to hospital with a diagnosis of CIDP. They had neurophysiological studies, sural nerve biopsy and other studies to rule out other diagnoses. The patients were assigned to the therapeutic protocols recommended. During 8 years of follow up we compared the response to treatment with intacglobin/plamapheresis, steroids and cytostatic drugs. RESULTS: It was highly significant (p< 0.001) that the patients with axon lesions on sural nerve biopsy did not respond to treatment with intac globin/plasmapheresis or steroids but did respond to cyclophosphamide, without any serious adverse effects being seen. CONCLUSIONS: Axonal histopathological lesions of CIDP at the onset of the disease may require cytostatic treatment since they do not usually improve on standard treatment. Sural biopsy is usually invaluable in such cases. PMID- 11785025 TI - [A ketogenic diet: is this a valid alternative in refractory epilepsy]. AB - INTRODUCTION: The ketogenic diet was first used in refractory epilepsy of childhood in the early 1920s. It was forgotten when new antiepileptic drugs were introduced, but recently has been used again. Although its efficacy in the treatment of epilepsy, in some patients, is beyond doubt, its mechanism of action is still not clear. There are three types of diet: the classical diet with a proportion of 4:1 of long chain fatty acids, with MCT oil and with modified MCT oil. OBJECTIVE: To present a protocol recently designed in our hospital. We include the type of diet, form of onset, subsequent follow up of complications, clinical and electroencephalographic response and side effects seen in the patients. PATIENTS AND METHODS: Introduction of the ketogenic diet with MCT oil in six patients aged between 2 and 11 years, with various types of epilepsy, all resistant to treatment, who had been unsuccessfully treated for 28 months in one case and between 4 and 6 months in the others. We evaluated the response on the criteria of Huttenlocher and Panic electroencephalograms. RESULTS: Two of the patients improved with good control of their disorder and the EEG became normal. No serious side effects were seen apart from gastrointestinal symptoms which improved when the quantity of MCT oil was reduced. CONCLUSIONS: In patients with drug resistant epilepsy it is convenient to have a guideline for treatment using a ketogenic diet. It is also useful to have a multi disciplinary team for management, follow up to detect late side effects and obtain the cooperation of the patient s family in following the protocol. PMID- 11785026 TI - [Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature]. AB - OBJECTIVE: To analyze the characteristics of hepatotoxicity due to ticlopidine. PATIENTS AND METHODS: We describe all the case of hepatotoxicity attributed to ticlopidine and reported to the Register of drug associated hepatopathies. We also obtained data from MEDLINE and the Spanish Medical Index regarding cases reported during the period 1982 2001. RESULTS: We reported twelve cases of hepatopathy related to the use of ticlopidine. These made up 5% of all the cases notified to the Register. Eighty three percent of the patients were male, and of an average age of 68 years. Sixty six percent required hospital admission. The latent period varied between 2 and 13 weeks. The liver lesion was of cholestatic type in 75% of the cases, hepatocellular in 16.6% and mixed in 8.3%. Twenty five percent of the patients had received sub therapeutic doses. CONCLUSIONS: Ticlopidine is often related to hepatotoxicity. This seems to be due to an idiosyncratic mechanism and is mainly cholestatic. The use of lower dosage than that recommended means that the desired therapeutic effect is not attained but does not protect against the development of hepatotoxicity. Doctors who use this drug should be aware of this so as to establish the true risk benefit relation. PMID- 11785027 TI - [Remission of epilepsy after onset of antiepileptic treatment: a prospective study in childhood]. AB - OBJECTIVE: To investigate the probability of achieving control of seizures after initiating treatment in childhood epilepsy. PATIENTS AND METHODS: 106 children aged under 14 years newly diagnosed of epilepsy were started on antiepileptic treatment and prospectively followed. RESULTS: Antiepileptic drug levels were monitored and compliance was satisfactory. The Kaplan Meier estimate of the probability of achieving a 2 year initial remission was 55%, 71%, 77%, 86% and 96% at 2, 2.5, 3, 4 and 5 years, respectively. Multivariate analysis using the Cox proportionate hazards model showed that a symptomatic etiology, an abnormal EEG and recurrence of seizures during the first six months of treatment reduced the probability of achieving a 2 year initial remission, while the presence of generalized tonic clonic seizures or partial secondarily generalized seizures exclusively and a patient age of 3 10 years increased it. Stepwise selection of the variables showed that the best model for prediction of remission was that composed of age 3 10 years and recurrence during the first six months of treatment. Differences among epileptic syndromes couldn t be demonstrated. CONCLUSIONS: Most children with epilepsy achieved a remission after initiating antiepileptic treatment. Those 3 10 years old or without recurrences during the first six months have a particularly favorable outcome. PMID- 11785028 TI - [Impairments in attention and facial emotion recognition in treatment of refractory and non refractory schizophrenics evaluated through an odd-ball paradigm]. AB - INTRODUCTION: Some of the processes impaired in schizophrenia are attention and emotional recognition. The aim of this study was to test: 1) if refractory schizophrenics (RS) present higher attentional deficits than non refractory (NR) evaluated through performance and the P300 amplitude in an odd ball paradigm using letters as stimuli; 2) if emotional recognition deficits in schizophrenics can be reflected by means of a similar paradigm than that used for letters, especially in RS, and; 3) if there exist a correlation between P300 amplitude and the level of psychopathology in these patients. PATIENTS AND METHODS: Performance and P300 amplitude were measured during a letter (LE) task and a similar one of facial emotion recognition (ER) applicating an odd ball paradigm, on 10 normal controls (CO), 10 NR and 10 RS. RESULTS: Reaction time was longer in both tasks and in LE, P300 amplitude was lower in NR and RS than in CO. In ER the RS showed a lower number of correct responses and higher of omissions than NR and CO, correlated with neuroleptics doses. A negative correlation between P300 amplitude and the scores of BPRS and PANSS positive symptoms scale was only found for the NR in ER. CONCLUSIONS: Present results point out that RS show similar deficits in relation to attention as NR do, but they show major deficits in emotional recognition related with neuroleptics doses. Furthermore, a lower P300 amplitude for NR was related to a higher level of psychopathology only in EF. PMID- 11785029 TI - [Neuropathy due to necrotizing vasculitis: a study of the clinical anatomy, neurophysiological characteristics, and clinical course of the disorder in 27 patients]. AB - INTRODUCTION: Peripheral neuropathy is usually one of the initial symptoms of necrotizing vasculitis. Early diagnosis is essential for good prognosis. OBJECTIVE: To determine which parameters are useful for early diagnosis and selection of tissue for biopsy. PATIENTS AND METHODS: We analyzed the clinical, biological, electromyographic and anatomopathological characteristics of 26 patients with necrotizing vasculitis and peripheral neuropathy. RESULTS: Twelve patients had panarteritis nodosa, three Churg Strauss syndrome, two Wegener s syndrome, two disseminated lupus erythematosis, one sarcoidosis and one Walderstrom s macroglobulinemia. Fifteen patients had multineuritis and the remainder distal mixed polyneuropathy which was symmetrical in three cases. In five cases biopsy was normal. Sural nerve biopsy showed the diagnosis to be correct in 20% of the patients. However, when this was done on a neurophysiologically affected nerve, the tissue was seen to be altered in 61%. Biopsy of the gastrocnemius increased the degree of usefulness to 73% when electromyographic anomalies were detected in this muscle. CONCLUSIONS: Neurophysiological study is essential for detection of alterations in patients clinically suspected of having necrotizing vasculitis, even in cases where there is apparently no neuropathy. We recommend biopsy of the gastrocnemius muscle as the first choice in cases where sural nerve neurography is found to be normal. If the sural nerve is not normal, it is the site of choice for biopsy, and muscle biopsy is the site of second choice. When both biopsies are normal, renal biopsy should be considered to establish the diagnosis, as a third alternative. PMID- 11785030 TI - [Fractures of the odontoid process. Incidence and treatment in the Neurosurgical Department of a hospital in Maputo (Mozambique)]. AB - INTRODUCTION: Fractures of the odontoid process make up between 10 and 15% of all cervical fractures. The decision as to when to operate on them is still controversial; the dilemma as to whether to use surgical or conservative treatment is still a problem. PATIENTS AND METHODS: We designed a descriptive study, which was prospective and applied to all patients diagnosed as having a fracture of the odontoid process, admitted to the Neurosurgical Department of Maputo Central Hospital (Mozambique) between June 1997 and May 1998. Follow up was rigorously controlled up to May 2000. All were treated conservatively with a cervical plaster collar. RESULTS: Six cases (83.3%), mainly male, were diagnosed. The patients were aged between 17 and 42 years, with an average age of 26.16 years. The commonest aetiology was a traffic accident (66.6%). Type II fractures were the commonest, seen in 4 patients. All patients complained of pain in the back of their necks. Dysparesia and brachial monoparesia were both seen in 33.3% of the patients. In four cases the fracture consolidated in three months, one in two months and the other after four months. Full recovery was made by 66.6%. CONCLUSIONS: Based on their review of the literature and own practical experience, the authors recommend conservative treatment for fractures of types I and II, immediate surgical operation for type IIA and for type II when the following conditions are met: displacement of over 4 mm, age of over 40 years and diagnosis made over a week after the injury had occurred. PMID- 11785031 TI - [Thalamic dementia due to infarct of the left thalamus and genum of the right internal capsule]. AB - INTRODUCTION AND OBJECTIVES: Thalamic dementia is the clinical consequence of a disorder of both thalami. It is generally secondary to bilateral paramedial thalamic infarcts due to disorders of small blood vessels or cardioembolism. We report a case of dementia of acute onset involving the left thalamus and the genum of the right internal capsule. CLINICAL CASE: A 33 year old man, HIV positive, category B2, admitted to hospital for tuberculous meningitis presented with the acute onset of somnolence, followed by marked bradypsychism, personality changes, marked disorder of executive explicit memory without associated praxic, gnosic or language disorders. Ocular motility remained normal. There was left central facial paralysis with inverse emotive voluntary dissociation. The other cranial nerves were normal. There was left hemiparesia with extensor plantar reflex. No other alterations. Cerebral MR imaging was compatible with paramedial infarcts of the left thalamus and genum of the right internal capsule. CONCLUSIONS: Thalamic dementia generally occurs in bilateral paramedian thalamic disorders. There are cases of disorders of executive memory secondary to infarcts of the genum of the internal capsule due to interruption of the thalamotemporal pathways and a contralateral paramedial thalamic lesion. PMID- 11785032 TI - [Regarding the clinical diagnosis of the monotopical spinal forms of multiple sclerosis. The value of the fan sign in the adult]. AB - INTRODUCTION: We wish to discuss the value of the clinical history and examination in orientation of the diagnosis of probable multiple sclerosis (MS). CLINICAL CASE: We report the two year study of a woman who over the previous ten years had had three episodes of paraesthesia, with pins and needles in her left leg and other parts of the left side of her body, although never affecting head or neck. She also complained of tiring more than usual. In an outpatient clinic she was found to have a syndrome affecting the upper segments of the spinal cord, mainly involving the right side and resembling an incomplete Brown Sequard type syndrome. There were increased clinical muscle and deep reflexes. The most marked was that of the right deltoid (C5), bilateral fanning of the toes when the Babinski reflex was tested, Barre positive in the right leg, pins and needles and dysaesthesia on the left to an undetermined level. Function was well preserved when compared with the clinical signs found. The case was considered to be of monotopical MS. Spinal magnetic resonance findings confirmed the clinical diagnosis. CONCLUSIONS: We emphasise the value of careful clinical investigation directed towards the diagnosis of probable MS. We draw attention to the diagnostic value of the dissociation between the severe clinical alterations and the functional performance, which was surprisingly well maintained. Also we report the originality of the presence of bilateral fanning sign supporting the diagnosis of MS, occurring in a disease of adult life. PMID- 11785033 TI - [Narcolepsy in children]. AB - INTRODUCTION: Narcolepsy is a neurological disorder characterized by excessive somnolence during the daytime, with recurrent, irresistible episodes of sleepiness. The complete forms are associated with cataplexy, hypnagogic hallucinations and sleep paralysis. The incidence reported in adults is 4 10/10,000. A considerable proportion of adults consider their disorder to have started before the age of 15 years. It is essential to have neurophysiological confirmation of the short period of the onset of REM sleep for diagnosis. CLINICAL CASE: An 11 year old boy with diurnal hypersomnolence, behavior disorder and weight gain. He was evaluated in the Sleep Disorder Unit by polysomnography and the multiple latency test, which confirmed the suspicion of narcolepsy. CONCLUSIONS: Narcolepsy is a disorder which starts during childhood and usually goes unnoticed or is erroneously diagnosed and treated. At the present time there are valid criteria for the identification and diagnosis of children with this disorder. Treatment of these patients should be orientated towards adaptation of the environment to the child and prevention of the psychosocial problems which may be caused by this disorder, in view of the poor response to the drugs used. PMID- 11785034 TI - [Bone morphogenetic proteins and cholinergic neurons in the central nervous system]. AB - INTRODUCTION: The discovery and characterization of factors that induce and maintain specific neurotransmitter phenotypes has profound clinical implications, and continues to be one of the major objectives in the neurosciences. DEVELOPMENT: Although much progress has been realized in this area, we still understand little of how cholinergic neurons acquire and maintain their neurotransmitter characteristics, nor do we fully comprehend why these neurons in some circumstances degenerate and loose their neurotransmitter specificity. There is evidence that some members of the bone morphogenetic protein (BMP) family have profound organizing and differentiating actions in the developing nervous system, and recent studies indicate an important role in determining the cholinergic neuronal phenotype. CONCLUSIONS: BMP may act to differentiate neuronal precursor cells into cholinergic neurons and upregulate the cholinergic phenotype of already differentiated neurons in the central nervous system. This could suggest their potential use in the treatment of certain types of brain disorders. PMID- 11785035 TI - [The theory of multiple intelligences: a suitable neurocognitive context for the neuropsychological hypotheses on the factors and mechanisms of superiority]. AB - OBJECTIVES: The aim of this article is to relate two theories regarding the structure of the human mind. We suggest that the theory of multiple intelligences, a neurocognitive theory of the psychologist Howard Garnerd provides a suitable context for theoretical understanding and validation of the hypothesis of the pathology of superiority, a neuropsychological hypothesis formulated by the neuropsychologists Norman Geschwind and Albert Galaburda. Similarly, we show that, apart from being a context, the first theory enriches the second. DEVELOPMENT: We review the essential elements of both theories together with the arguments for them so that the reader may judge for himself. Similarly we review the factors determining intelligence; the association between neuropathology and intellectual dysfunction, general and specific, and the new directions in the understanding of human cognition. CONCLUSIONS: We propose to consider the first theory as a fertile ambit and broad methodological framework for investigation in neuropsychology. This simultaneously shows the relevance of including neuropsychological investigation in broader cognitive and neuropsychological theories and models. PMID- 11785036 TI - [Idiopathic partial epilepsy syndromes]. AB - OBJECTIVE: In this paper we wish to review the main characteristics of idiopathic partial epilepsy syndromes recognized in the International Classification of epilepsies and epileptic syndromes and of other syndromes which have been described but not yet included in this classification, with special emphasis on the clinical condition, electroencephalographic aspects and progress. DEVELOPMENT: The idiopathic partial epileptic syndromes are characterized by the absence of a subjacent cerebral lesion and neurological or intellectual deficit. In most cases there is a definite genetic predisposition. There is often a family history of benign epilepsy. The seizures usually start after the age of 18 months. The interictal EEG shows basically normal activity but focal epileptic discharges are often seen. CONCLUSIONS: There are many idiopathic partial epileptic syndromes. However, most of them are not included in the International Classification of the epilepsies and epileptic syndromes. We believe that further study is necessary and consider that when more cases are reported and with continual advance of genetic studies there will be a consequent improvement in understanding of these syndromes and they will be included in the International Classification of epilepsies and epileptic syndromes. PMID- 11785037 TI - [Dopamine agonists situation in Parkinson disease]. AB - The development of a variety of side effects associated with long term treatment of Parkinson s disease has prompted the introduction of new drugs and new treatment strategies. The use of dopamine agonists in combination with levodopa has proved to be useful in advanced patients with motor fluctuations. Recent studies indicate that the use of dopamine agonists in monotherapy from the early stages of the disease can be as effective as levodopa for clinical improvement with the added advantage of a significant less presentation of diskinesias. Ropinirol the first dopaminergic agonist demonstrating this effect in a 5 year controlled study, has well tolerance, both in combination or in monotherapy. Although low doses can be useful for individual patients, doses of approximately 15 16 mg/day proved to be safe and effective in long term studies. PMID- 11785038 TI - [Prenatal diagnosis and carriers in families with Duchenne muscular dystrophy. The introduction of new markers]. PMID- 11785039 TI - [Clinical characteristics of drug induced parkinsonism in psychotic patients]. PMID- 11785040 TI - [Early recurrence of ischaemia in a patient with cerebral haemorrhage due to moya moya disease]. PMID- 11785041 TI - [Aetiology of epilepsies of late onset]. PMID- 11785044 TI - [Alpha coma: clinical, electroencephalographic and aetiological correlation in childhood]. AB - INTRODUCTION: Alpha coma is defined as the appearance, in an unconscious patient, of EEG activity in the alpha frequency band (8-13Hz). OBJECTIVE: To determine, in our setting, the incidence, aetiology, clinical significance and course of alpha coma in paediatric patients and review the literature. PATIENTS AND METHODS: We did a retrospective study of the patients admitted to a paediatric intensive care unit who had alpha activity recorded whilst in coma. RESULTS: Only two patients, aged 5 and 12 years, were found. Both had complex congenital cardiopathy and cardio-respiratory arrest one and twelve days postoperatively, respectively. Several EEGs were done whilst they were in coma. Barbiturate coma was not used. Both had clinical mid-brain involvement during alpha recording. The pattern was bilateral, arreactive and preceded by a theta pattern, appeared two days after the arrest, was maintained for two and three days in the two cases and was followed by delta pattern. The second case finally showed a 'burst-suppression'. The CAT was normal. The patients died 4 and 11 days after the appearance of alpha coma. CONCLUSIONS: Alpha coma is rare in childhood. Both the aetiology and the bad prognosis are similar to that of adults. Alpha coma is a transient EEG pattern occurring during the evolution of coma. We consider it to be due probably to mid-brain involvement. PMID- 11785045 TI - [Pseudotumor cerebri: analysis of our cases and review of the literature]. AB - INTRODUCTION: Pseudotumor cerebri (PC) is a complex syndrome characterized by increased intracranial pressure in the absence of any space occupying lesion, usually self limiting, but often relapsing. Diagnosis is based on a record of intracranial pressure of over a limit of 250 mmH2O. Morbidity is basically due to possible loss of vision associated with atrophy of the optic nerve. When the aetiology is unknown this clinical condition is known as idiopathic intracranial hypertension. PATIENTS AND METHODS: We describe the principal characteristics of a series of patients who were admitted to our department with the diagnosis of PC and review the relevant literature. RESULTS: Altogether 14 patients (12 women and 2 men) were admitted with the diagnosis of PC. In 12 patients the disorder presented with headache, with or without associated symptoms of disorders of vision. The main visual symptoms were transient darkening of vision, scotomas, photopsias and reduction in visual acuity. The headache was holocranial, continuous and well tolerated or alternatively uni or bilateral, pulsatile, moderate, with or without photophobia, and with or without nausea and vomiting. Bilateral papilloedema was seen in all patients. In one case there was also bilateral facial palsy and neck rigidity. In four cases visual field measurement were abnormal (inferoneasal scotoma, bilateral concentric reduction). Progress was poor in only one case. CONCLUSIONS: In spite of being theoretically benign, and there being many forms of treatment, PC may cause considerable morbidity of vision. Therefore, early diagnosis and close follow up attention is essential. PMID- 11785046 TI - [Standards for carrying out and interpreting visual evoked potentials in children]. AB - INTRODUCTION: An essential step, prior to the introduction into paediatric practice of visual evoked potentials (VEP) caused by stimulation with light emitting diodes (LED) is their description at different stages of maturity of the nervous system. PATIENTS AND METHODS: We obtained VEP to LED in a group of 60 children aged between 1 and 5 years, who were functionally healthy and equally distributed with regard to age and sex. In each case we recorded the responses to monocular stimulation (right and left), binocular stimulation and without stimulation (replicas of each condition). The recordings were made under sedation with secobarbital at a dose of 3 mg/kg body weight. RESULTS: Our results showed a significant reduction in the latency of all components (except P3) and the amplitude of N1 and P1, as a function of the age of the child. The response to LED is reproducible (especially intra individual) with up to three types of morphology observed. Sedation did not affect detection of the response. The only significant effect was a reduction in the amplitude of P1. CONCLUSIONS: We confirmed the changes due to maturity, reflected in a significant reduction of the latency of most components with increasing age. By between 4 and 6 years old the figures obtained were similar to those in adults. The results obtained give us the opportunity chance of publishing this standard data so that better use and interpretation of VEP to LED at an early age may be possible. PMID- 11785047 TI - [Epidemiological characteristics of a group of multi organ donors used to transplant organs in Cuba]. AB - INTRODUCTION: For current transplants, the organ donor is a basic factor. OBJECTIVES: To determine the demographic characteristics of the donors used in the Cuban liver transplant programme, the main causes of brain death, most widely used amines and serology pattern. To report the transplants carried out. PATIENTS AND METHODS: We reviewed the clinical histories of the actual donors processed between July 1999 and July 2000. RESULTS: During the period studied 13 actual donors were used: 9 men (69.2%) and 4 women (30.8%) distributed in the following age groups: 15 30 years: 3 cases (23%); 31 45 years : 4 cases (30.8%); 46 60 years: 5 cases (38.5%), and over 60 years: 1 case (7.7%). We did 42 transplants: 12 liver, including the first hepato renal in Cuba, 18 kidney, 10 cornea, and 1 heart. The causes of death were: head injury: 10 (76.9%), and hemorrhagic cerebral vascular accident: 3 (23.1%). Only 3 cases (23.1%) did not require the use of vasoactive amines. These were used in the other 10 (76.9%). The most commonly used were dopamine and epinephrine, in 6 cases each (46.1%). In the serological studies for immunoglobulin G for cytomegalovirus all 13 were positive, Epstein Barr virus 6 (46.1%), toxoplasma 12 (92.3%), herpes virus 1: 13, herpes virus 11: 13. CONCLUSIONS: The typical donor was a man aged 46 60 years with brain death due to head injury following a road traffic accident. A large proportion of donors required the use of amines to maintain hemodynamic stability. There was a large proportion of patients who were found on microbiological serology studies to test positive. PMID- 11785048 TI - [Giant evoked potentials]. AB - INTRODUCTION: There are many, diverse nosological entities with the common factor of the genesis of cortical evoked potentials of great amplitude, commonly known as giant evoked potentials. In most cases they are conditions with the common clinical condition of myoclonic of cortical origin, such as progressive myoclonic epilepsy, generalized idiopathic epilepsy, myoclonias of toxic, infectious or postanoxic origin. Giant potentials have been shown both in studies of focal hemisphere lesions and in some cases of patients with corticobasal degeneration. OBJECTIVE: The aim of this paper was to show, by presenting interesting cases, some of the conditions mentioned and to review some concepts concerning the mechanisms which may be involved in the production of these electrophysiological responses. PATIENTS AND METHODS: We studied 6 patients aged between 2 and 22 years, in whom multimodal evoked potentials, electroencephalograms and imaging studies had been done. RESULTS: Giant somatosensory potentials were shown in the patients with obvious myoclonia. Visual potentials of great amplitude were common to the other patients presented, with or without myoclonia. CONCLUSION: Giant evoked potentials respond to a state of cortical hyperexcitability which may have various causes. PMID- 11785049 TI - [Long term potentiation at marrow level induced through EMG biofeedback]. AB - INTRODUCTION: The long term potentiation (LTP) of synaptic transmission constitutes a remarkable example of synaptic plasticity, and represents a learning model. The LTP has been described by several authors in the hippocampus through high frequency stimulation. OBJECTIVES, PATIENTS AND METHODS: In the present paper we have used conventional EMG biofeedback techniques which aims at investigating the rehabilitation of myopathies and the electrophysiological mechanism of neuromuscular learning at marrow level. Three experimental patients of progressive muscular dystrophy, aged between 11 and 15, were systematically treated with EMG biofeedback in several muscular groups. Special attention is given to the records corresponding to rest post maximum effort (RPME). RESULTS: For the principal muscular groups rehabilitated it has been verified that the motor unit potentials corresponding to RPME show intense activity, with average amplitudes of 600 700 mV and duration close to 15 ms, against a practically nonexistent activity before rehabilitation. The descent of the alkaline phosphatase (from 200 U/l to 50 U/l) and the lactic deshydrogenase (from 320 U/l to 210 U/l) are specially significant. CONCLUSIONS: The EMG biofeedback techniques allow us to improve physical efficiency in patients of progressive muscular dystrophy. The analysis of post biofeedback motor unit potentials, and the strong descent of the enzymes in the last phase of treatment, allows us to deduce the establishment of LTP between the alpha motoneurons and the axonic terminals of the microneurons of Renshaw. The mechanism of the LTP at marrow level is interpreted through two physiological hypotheses concerning the circuit of Renshaw. PMID- 11785050 TI - [Spinocerebellar ataxia type 2 in Cuba. A study of the electrophysiological phenotype and its correlation with clinical and molecular variables]. AB - INTRODUCTION: The spinocerebellar ataxia type 2 has a prevalence of 43 per 100,000 inhabitants in Holguin province, which is the highest one reported worldwide. It is due to an intergenerational CAG repeat expansion contained in the first exon of disease causing gene, and it is characterized by a high variability in its clinical and electrophysiological presentation, even intrafamiliarly. OBJECTIVE: Factors identification, which explains this variability, could lead to the findings of therapeutical ways that may retard the disease onset. PATIENTS AND METHODS: We have done this research in order to contribute to this phenotypic variability knowledge of the different structures and functions of the nervous system. RESULTS: By means of molecular and electrophysiological studies we have found two groups well differentiated in a 52 patient sample. The first one was characterized by CAG repeat expansions above 41 units and by the total blockade of the afferent conduction that is, basic electrophysiological alteration with axonal damage predominance. The second one was characterized by CAG repeat expansions lower or equal to 41 units and showed a high variability in it s electrophysiological behavior with myelinic damage predominance. We realized of the existence of statistical significance correlations between the electrophysiological, clinical and molecular variables considered. CONCLUSIONS: These findings suggest that for by CAG repeat expansions lower or equal to 41 units should be affecting other genetics and/or environmental factors that explain the variability found in this group which are not significant for clinical and electrophysiological presentation in individuals with CAG repeat expansions above 41 units. PMID- 11785051 TI - [Statistical analysis of repetitive nerve stimulation test]. AB - INTRODUCTION: Statistical properties of Repetitive Nerve Stimulation test (RNS) are studied for different variables (forth to first potentials ratio of CMAP) together with two new variables (trends of area and amplitude for series of CMAP) OBJECTIVE: To compare the variables commonly used, in order to define the best statistical properties and, in the other hand, investigate if the new variables (trends in area and amplitude) could be useful for the study of neuromuscular transmission pathology. SUBJECTS AND METHODS: Statistical properties of voltage (V4/V1(V)), area of CMAP (V4/V1(a)) and slopes of regression lines of voltage (m(V)) and area (m(a)) measures are determined for runs of 3, 10, 15 and 20 Hz series of stimuli in 13 men and 17 women healthy volunteers. RESULTS: 1) The sample fits well to a normal distribution; 2) The variables that measure tendencies in CMAP series, can be reasonably fitted to linear regression functions; 3) Differences between sex and age have been not found; 4) Variables measuring tendencies have been the most stables, specially m(a); 5) The variable that fits better to normal distribution is m(V); 6) All variables behave linearly with respect frequency of stimulation. CONCLUSIONS: 1) Neuromuscular transmission is a particularly stable physiologic function; 2) The most used variable in clinical neurophysiology laboratories, V4/V1(V) have the worst statistical properties, showing a very significant variability; 3) Trends measures (m(a)) and m(V)) show very satisfactory statistical properties; this implies that these could be very useful for the study of neuromuscular transmission diseases. PMID- 11785052 TI - [Cerebral infarct in childhood as a complication of migraine with aura. A case report]. AB - INTRODUCTION: A migrainous infarct is a complication which may occur during the course of an attack of migraine, especially during the phase of the aura. It is the cause of between 1 and 14% of the cerebral infarcts in children. Even today there is still controversy as to whether it occurs in childhood, in spite of a strongly based clinical suspicion of it, since it is difficult to prove the chain of clinicopathological events scientifically. CLINICAL CASE: We report the clinical case of an adolescent girl of eleven years of age who complained of having attacks of migraine with aura for the previous two years and fulfilled the criteria of the International Headache Society (IHS). She was referred to us when a cranial CAT scan showed a hypodense area at the level of the ganglia of the left base, although neurological examination was still normal. The probable ischaemic nature of the lesion was confirmed using neuroimaging techniques (magnetic resonance). On electroencephalography there was a slow focal pattern which was moderately persistent in the left temporal cortex. Other causes of cerebral infarct were rules out on further complementary studies. CONCLUSIONS: The patient therefore fulfilled the criteria of the IHS for diagnosis of a migrainous infarct. We also analyze the main findings regarding clinical history, epidemiology, clinical findings and diagnosis of migrainous infarct in childhood. PMID- 11785053 TI - [Hyperattentional syndrome in children]. AB - INTRODUCTION: The attentional mechanism is complex, it depends of multiple encephalic structures, acting all of them together. While using the attentional mechanism we accumulate information from the outside world, this trough the memory of work. The frontal lobe s integrity allows the development of the learning and attentional mechanism, its malfunction is associated with the attention deficit hyperactivity disorder. The attention is generally selective to different kind of stimuli. In this disorder the children have fixed and sustained visual to a variety of stimuli. CLINICAL CASES: We present three children, with vigilant alterations characterized on having uniform selective visual attention to stimuli from the exterior, with prolonged latency. Without any other neurological manifestation. CONCLUSIONS: Children with attentional deficits, generally present selective attention to certain outside world stimuli. The hyperattentional disorder is a variety of selective visual attention with prolonged latency on the object selected. PMID- 11785054 TI - [A case of Isaacs' syndrome associated with dextrocardia]. AB - INTRODUCTION: Isaacs syndrome is a disorder of unknown etiology characterized by muscular rigidity, cramps and myokymias. Described by Isaacs in 1961 and called by him as continuous muscular activity syndrome. There are few reports in Latino american countries. CLINICAL CASE: A 31 year-old man with sustained muscular contractions in lower limbs and diffuse myokymias since he was eighteen-year old. Dextrocardia was disclosed on clinical examination. CONCLUSION: We report the case of a patient with Isaacs syndrome and dextrocardia. PMID- 11785055 TI - [Subacute combined degeneration. A description of the case of a strictly vegetarian child]. AB - INTRODUCTION: Cyanocobalamin (vitamin B12) is an essential cofactor of various metabolic pathways. Lack of it leads to symptoms which may be constitutional, of skin or mucous membranes, hematological or neuropsychiatric disorders. Neurological involvement in adults has been well described and analyzed in the literature, however there are fewer cases of children. In the cases described in children the deficiency was related to maternal malnutrition, and socioeconomic and cultural problems. Since vegetarianism is a custom followed by different social groups we wish to draw attention to this as a cause of vitamin B12 deficiency and the neurological disorder this may cause. CLINICAL CASE: We describe the case of a 10 year old boy, a member of a religious community who were strict vegetarians. Over three months he developed: a cognitive disorder, pyramidal syndrome of his legs, involvement of the posterior spinal cord, peripheral motor and sensory alterations which, together with the complementary investigations, was found to be compatible with subacute combined degeneration due to vitamin B12 deficiency. CONCLUSION: We draw attention to the clinical and laboratory aspects of this disorder and the importance of taking the possibility of this diagnosis into account in children with nutritional risk factors. PMID- 11785056 TI - [On the function of dendritic filopodia]. AB - INTRODUCTION: Dendritic spines were first described by Ramon y Cajal in 1888, and considered by him to be the major sites of axo dendritic apposition and therefore of synaptic input in the CNS. Although a considerable wealth of information has been gathered over the last few decades about the function of spines in the mature nervous system, much less is known about how spines first appear on the otherwise smooth dendritic shafts. DEVELOPMENT: The earliest dendritic appendages, known as filopodia, are long and thin protrusions that occur predominantly during early postnatal development of the mammalian CNS. It is tempting to consider filopodia simply as precursors to spines because at first glance their overall shape is similar to that of mature spines and because their expression during development precedes that of spines. However, the elongated shape of dendritic filopodia (reminiscent of that of axonal filopodia and filopodia in non-neuronal cells) suggests an exploratory function, so that their role may be to contact axons in order to establish early synapses, independently of the eventual formation of spines. CONCLUSIONS: Here we review the literature on dendritic filopodia in an attempt to resolve this issue regarding these two distinct (though potentially overlapping) roles of filopodia in development: spinogenesis vs synaptogenesis. We summarize what is known about the physical characteristics and developmental time course of filopodia expression, as well as the mechanisms of growth and motility of these early dendritic protrusions, both in the intact nervous system and in pathologic settings. Throughout this review we present evidence that supports two hypotheses: that filopodia and spines are two inherently different types of protrusions, and that the role of dendritic filopodia is to capture axons and make early synapses, rather than transform into spines. Finally, we also discuss the potential role of filopodia in the sculpting of the dendritic tree. We also postulate that filopodia have additional important roles in regeneration and repair, in developmental plasticity and in the elaboration of dendritic arbors. These functions may not be limited to a specific developmental period, but probably extend into adulthood. We end by discussing specific experiments that could serve to test these hypotheses. PMID- 11785057 TI - [Benign partial epilepsies of childhood]. AB - OBJECTIVE: To carry out, by means of a literature review, an update of the entities that can be included within the group of benign partial epilepsies of childhood. DEVELOPMENT: Among partial epilepsies with onset in the first stages of life, a group extended in the last years with a favourable course and a trend to reverse, even spontaneously, has been identified. Some of these entities have a genetic origin but we do not know the mechanisms by which these epilepsies show a self limited course, which have given rise to the denomination of epilepsy that comes and goes; nevertheless, an evolution to other more complex forms is also possible. CONCLUSIONS: Benign partial epilepsies of childhood constitute a wide group of conditions of varied semiology, usually with a good prognosis even without treatment. Occasionally, these epilepsies may show a more unfavourable course with a worsening, in spite of medication, and the appearance of neurologic and neuropsychologic disorders. All these aspects must be known and considered by the physician in charge of these patients management. PMID- 11785059 TI - [Diagnosis of cervical spondylitis disease: An evidence based review]. AB - INTRODUCTION: The diagnosis of cervical spondylitis (CS) is based on three factors: clinical, neuroradiological and neurophysiological data. However, in spite of being universally used, the validity of each of these diagnostic instruments has still to be clarified. The objective of our study was to make a critical analysis of the evidence currently available with regard to the diagnosis of CS. DEVELOPMENT: Review of the literature from 1967 to March 2001, quoted by MEDLINE, regarding the diagnosis of CS. The articles obtained were classified into four groups: Metanalysis or systematic reviews, controlled studies with a surgical pattern of reference, controlled studies with another pattern of reference or not controlled and cases or series of cases. We made a critical analysis of each of the articles obtained. CONCLUSIONS: There is no clinical test or investigation which may be considered to be a definite diagnostic marker, so the degree of diagnostic certainty depends on the combination of investigations and their agreement with the clinical history and examination. The data from clinical examination may be considered to be extremely useful in the diagnosis of CS. Neuroimaging investigations are characterized by their high sensitivity and low specificity, so these methods should be used early in the process of making a diagnosis of CS. The myelo CAT scan is better than MR in the diagnosis of spondylitic cervical radiculopathy (SCR). The new MR techniques have considerably improved the possibilities of diagnosis of SCR, but there is no evidence that they are currently as good as the myelo CAT scan. MR is the method of choice for assessment of intrinsic spinal disorders, although there is some evidence that the degree of cervical stenosis may be underestimated when MR is used. The neurophysiological diagnosis (EMG) in SCR is of high specificity since it gives only a small proportion of false positive results. Somatosensory evoked potentials (PESS) from the tibialis posterior is a highly sensitive test for the diagnosis of spondylitic cervical myelopathy (SCM). The combination of PESS and motor evoked potentials may be useful for the detection of patients with SCM at presymptomatic stages and for differentiation between spinal and root involvement. It is essential to carry out studies to evaluate the available diagnostic tests based on specificity. These studies should be the first step in making it possible to design studies to determine the natural history of CS and the therapeutic effectiveness of the techniques currently in use. PMID- 11785058 TI - [Epilepsy and pregnancy]. AB - INTRODUCTION: Treatment of the epileptic patient during pregnancy poses a major clinical dilemma. For one thing the patient has to be kept free of seizures, but she also should be kept on monotherapy at the lowest possible dose, due to the effect such medication may have on the unborn child. DEVELOPMENT: There is a syndrome related to intra uterine exposure to the classical antiepileptic drugs, but which is not associated with any particular drug. However, the effect of the new antiepileptic drugs on unborn children is still unknown. To date, no specific pattern of malformations has been described in relation to any of these drugs. Lamotrigine is the one with which there is most clinical experience. Although there are still not enough cases studied to permit definite conclusions to be drawn, at the moment the incidence of congenital anomalies is the same as in the general population. CONCLUSIONS: The new anti-epileptic drugs have a major therapeutic advantage, not only in the management of epilepsy in different clinical situations, but also in the good results observed when using lamotrigine in patients of fertile age. PMID- 11785060 TI - [Chronic demyelinizing polyneuropathy associated with diabetes mellitus. A case report]. PMID- 11785062 TI - [Babinski s reflex, yes; Babinski s sign no; Pseudobabinski never]. PMID- 11785061 TI - [Hyperdense cerebral abscess. A case report]. PMID- 11785064 TI - Pathophysiology of essential hypertension: role of the pump, the vessel, and the kidney. AB - Essential hypertension is characterized by significant and persistent elevations in arterial pressure. Hypertension is a multifactorial disorder that may involve abnormalities in the functions of the heart pump, the blood vessels, and the kidneys. Short-term and long-term regulation of arterial pressure is influenced by changes in cardiac function, the peripheral vascular resistance, and the renal control mechanisms of plasma electrolytes and volume. Increases in the heart rate and stroke volume lead to increases in the cardiac output and could contribute to increases in arterial pressure particularly in relatively young individuals. Vascular endothelial cell dysfunction could lead to reduction in endothelium derived relaxing factors such as nitric oxide, prostacyclin, and endothelium derived hyperpolarizing factor, or increased production of contracting factors such as endothelin-1 and thromboxane A2. Also, increased activity of signaling pathways of vascular smooth muscle contraction such as [Ca(2+)]i, protein kinase C, mitogen-activated protein kinase, and Rho kinase could enhance vasoconstriction. The decreased vascular relaxation and excessive vasoconstriction lead to significant increases in the peripheral vascular resistance and arterial pressure over time, particularly with aging. Alterations in body fluid regulation by the kidneys could lead to salt and water retention, increased plasma volume, and cardiac output. Also, activation of the renin angiotensin system increases the levels of angiotensin II in the plasma, leading to generalized vasoconstriction, or locally in the kidneys, leading to salt and water retention. Individual changes in cardiac, vascular, or renal function seldom occur separately, and, if so, they may lead to mild or moderate increases in arterial pressure. Combined alterations in cardiac, vascular, and renal functions are more common and are often associated with pathologic increases in arterial pressure and established hypertension. PMID- 11785065 TI - Pathophysiology of hypertension in renal failure. AB - Hypertension (HTN) is ubiquitous in the renal failure patient. It has long been thought that renal disease interferes with salt excretion, leading to volume overload and consequent hypertension. This theory gives prominence to the kidney in long-term regulation of blood pressure (BP). It is assumed that the excess salt and water retention increases the blood flow to the tissues, which sets in motion the phenomenon of autoregulation. The tissue arterioles vasoconstrict to decrease the excessive blood flow. The resulting vasoconstriction raises the peripheral vascular resistance, which is the cardinal most consistent findings in HTN (whether essential or renal in origin). Recently, more light has been shed on the multitude of factors and pathophysiologic mechanisms that lead to HTN in the renal disease patient. The level of BP is most likely determined by the level of the peripheral vascular resistance and volume status in combination. If the peripheral vascular resistance is not appropriately lowered in the face of hypervolemia, HTN results. This primary role of the blood vessel in HTN is consistent with the close correlation of vascular disease to HTN (because HTN is a manifestation of vessel disease). In this review, evidence for and against the different pathophysiologic mechanisms that have been postulated to explain renal HTN is presented. PMID- 11785066 TI - The genetics of human hypertension. AB - Human hypertension is a common and complex disease and is associated with diabetes, cardiovascular, and renal disease. Therefore, it is important to understand the genetic basis of this disease. Specific genetic mutations leading to monogenic forms of hypertension have been identified in Liddle's syndrome and glucocorticoid-remediable hypertension and in some syndromes in which blood pressure is lowered. Because essential hypertension is a polygenic disease, elucidating a genotype that is causally related to essential hypertension will be difficult. To date, no genotype has been conclusively linked to essential hypertension except in certain populations. However, there has been progress in finding genetic variations that are associated with hypertension in patients with components of the metabolic syndrome (or Syndrome X). Future discoveries in this area should enhance our ability to intervene earlier and more effectively and therefore lessen the complications of this common disease. PMID- 11785067 TI - The role of lifestyle management in the overall treatment plan for prevention and management of hypertension. AB - Hypertension is the most common cardiovascular risk factor in the U.S. population, and hypertensive nephrosclerosis is a common cause of progressive renal disease. Dietary and lifestyle modifications have shown promise in enhancing the effectiveness of blood pressure (BP) management. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNCVI) includes recommendations for prevention and management of hypertension. Recommendations include reducing sodium intake, increasing potassium, calcium, and magnesium intake, controlling obesity, and avoiding heavy alcohol intake, along with aggressive BP control. JNCVI guidelines provide a reasonable approach to lifestyle interventions, the benefits of which would outweigh the antihypertensive effects. The data suggest that such guidelines would benefit normotensive people as well. PMID- 11785068 TI - Pathophysiology of adrenal hypertension. AB - Hypertension affects 20% to 25% of the adult population. Most patients are diagnosed as having essential or primary hypertension. Up to 10% to 15% have an identifiable cause and many of those have an adrenal basis. The identification of an adrenal cause of hypertension provides an opportunity for a targeted therapeutic intervention. Mineralocorticoid hypertension refers to hypertension caused by increased sodium and water retention by the kidney, expansion of the extracellular fluid compartment, and direct effects on the vasculature and circumventricular areas of the central nervous system (CNS), which result in elevation of blood pressure. The most common form of mineralocorticoid hypertension (MCH) is primary hyperaldosteronism (PA). In the past decade, significant advances have been made in our understanding of the pathogenesis of low-renin hypertension with the elucidation of the genetic basis and characterization of 3 forms of monogenic hypertension: glucocorticoid-remediable aldosteronism, syndrome of apparent mineralocorticoid excess, and Liddle's syndrome. This article focuses attention on the role of steroid hormones in the pathogenesis of hypertension and outlines the pathophysiology of the different forms of adrenal hypertension. PMID- 11785069 TI - Preeclampsia: pathophysiology and practice considerations for the consulting nephrologist. AB - Abnormal placental implantation presumed to be secondary to maternal genetic susceptibility or immune maladaptation is considered to be fundamental to the pathogenesis of preeclampsia. The reduced placental perfusion resulting in placental ischemia is hypothesized to cause the known endothelial dysfunction, which leads to the clinical manifestations of this disease. Oxidative stress is a postulated linking factor, an aberration that possibly has its genesis via cytokines released from the abnormally implanted and perfused placenta. Clearly the maternal pathophysiologic changes that subsequently produce what is recognized as preeclampsia are present long before the disease makes its clinical appearance. PMID- 11785070 TI - Pathophysiology of hypertension in the elderly. AB - The importance of hypertension as a cardiovascular risk factor increases progressively with aging, but diastolic blood pressure plateaus at age 50, which leads to a rise in pulse pressure in the elderly. Thus, isolated systolic hypertension with a widened pulse pressure is the most common type of hypertension seen in persons older than 65 years of age. Pulse pressure is the most robust blood pressure measurement in predicting cardiovascular disease. This rise in systolic blood pressure and pulse pressure with aging is a consequence of arterial stiffness. With aging, both structural and functional changes occur that result in a less compliant aorta and large vessels. Investigators who use pulse wave velocity and augmentation index as measures of large artery stiffness have repeatedly shown an increase in arterial stiffness with aging. Early return of the reflected pulse wave to the aorta during systole has been shown to be the primary mechanism accounting for the rise in systolic and decline in diastolic pressure that occurs with arterial stiffness. Several factors have been shown to decrease arterial stiffness including aerobic exercise, decreased sodium intake, n-3 fatty acids, estrogen replacement therapy, nitrates, and ACE inhibitors. Drugs that specifically lower systolic blood pressure but not diastolic pressure, such as vasopeptidase inhibitors, are under investigation in treating isolated systolic hypertension. PMID- 11785071 TI - Sleep apnea and hypertension: pathophysiologic mechanisms. AB - This article reviews the pathophysiology of hypertension (HTN) in obstructive sleep apnea (OSA). The article is divided into 3 sections. The first section describes epidemiologic studies of the relationship of sleep-related breathing disorders, including OSA, to HTN and argues that OSA contributes to the genesis of HTN. The second section describes the known immediate physiologic consequences of 3 components of OSA that may contribute to the genesis of persistent systemic HTN. The 3 components are (1) the large negative intrathoracic pressure changes associated with OSA, (2) intermittent hypoxemia, and (3) arousal from sleep. The last section reviews current physiologic models of essential HTN genesis and attempts to integrate them with the suspected HTN-generating aspects of OSA. In its summary, the authors conclude that OSA contributes to the genesis of HTN and advise physicians not to ignore the contribution of frequently comorbid non-OSA factors, such as obesity, to the genesis of OSA-related HTN. PMID- 11785072 TI - [Low-intensity laser irradiation in patients with urinary tuberculosis]. AB - Combined surface radiation of renal projection area and intravascular laser radiation of blood (AZOR-2K unit) were used in combined treatment of 54 patients with urinary tuberculosis. Analysis of immunological and hematological indices of peripheral blood of patients before and after the combined treatment showed that low-intensity laser radiation activates local system of T-helpers which after specific antigenic impact differentiate into T-helpers-1. The latter synthesize in loco gamma-interferon, TNF-alpha and beta and IL-2 stimulating bactericidal mechanisms directed at destruction of M. tuberculosis and resolution of the infection focus. PMID- 11785073 TI - [Diferelin treatment of primary local and generalized cancer of the prostate]. PMID- 11785074 TI - [Preliminary results of casodex use in patients with hormone-resistant cancer of the prostate]. PMID- 11785075 TI - [Cryodestruction of the anterior lobe of adenohypophysis in terminal patients with prostatic cancer]. AB - The authors used a new method of treatment of prostatic cancer--selective stereotactic puncture cryodestruction of the anteriod hypophysis lobe--which prevents water-electrolyte imbalance, relieves pain syndrome due to bone metastases, reduces androgenic stimulation of the prostate, improves quality of life for patients of clinical group IV. The operation is low-traumatic and is not accompanied with serious complications. PMID- 11785076 TI - [Three-dimensional ultrasonic visualization in the diagnosis of prostatic diseases]. AB - Three-dimentional (3D) ultrasound investigation (USI) covered 60 patients with various prostatic diseases. 3D USI was made with a computer tomographic device "Echotom-3D" allowing getting three-dimentinal images on two-dimentional scanners as well as 1846 scanner ("B&K Ultrasound Systems", Denmark), sensors 3.5, 5.0 and 7.0 MHz. Transabdominal, perineal and transrectal 3D USI were performed. These proved highly effective in diagnosis of prostatic diseases. PMID- 11785077 TI - [Plasmapheresis in combined treatment of acute rejection crises after kidney transplantation]. AB - The aim of the study was assessment of effectiveness and safety of extracorporeal procedures (plasmapheresis) in prevention and combined treatment of acute rejection crises (ARC) after kidney transplantation in patients at high risk to develop acute immunological conflicts in early postoperative period. 94 patients aged 21-56 years after allotransplantation of cadaver kidney (ATCK) entered the study. They were divided into two groups: group 1 patients (n = 47) received plasmapheresis procedures in combined preventive and therapeutic treatment of ARC; matched group 2 patients (n = 47, retrospective) received the same therapy but plasmapheresis. In both groups there were many patients with a high titer of pre-existing antibodies and massive hemotransfusions in the past. The analysis covered also recipients with the second ATCK (9 and 4 patients, respectively). After ATCK both groups received three-component immunosuppressive treatment (neoral, prednisolone, azatioprin and/or sell-cept). The analysis of the transplant and recipient 11-month survival has estimated that it was 93.6 and 91.5% for the recipients, respectively, and 91.5 and 76.5% for the transplanted kidney for group 1 and 2, respectively. The conclusion is that plasmapheresis in combined prevention and treatment of ARC by humoral type in sensitized patients (high titer of the pre-existing antibodies, repeat transplantations, hemotransfusions) is pathogenetically grounded and lowers the percentage of irreversible episodes of acute transplant rejection early after surgery. PMID- 11785079 TI - [Effects of sodium hypochlorite on the course of recovery of structural elements and functions of the kidneys in postischemic period]. AB - Kidney morphological structure, function and enzymuria were studied in experiment on 22 non-inbred rats of 200-280 g body weight with 90 min kidney ligature ischemia on day 3 and 7. In experimental group (11 rats) 1 ml 0.06% solution of sodium hypochlorite (SH) was injected intraperitoneally daily after kidney ischemic damage. 11 rats of the control group received 1 ml 0.89% SH solution in daily intraperitoneal injections. Morphological changes in renal structure, functional capacity of the kidneys, enzymuria on experimental day 3 and 7 were studied. It was revealed that SH injected in acute ischemic phase aggravated kidney cell damage. However, SH induced kidney reparative reaction on day 3. In the control group this reaction was registered only on day 7. It is suggested that SH may be an effective prophylactic modality against ischemic renal damage. PMID- 11785078 TI - [Diagnostic significance of parameters of enzymuria, lipid peroxidation and excretion of middle molecular toxins in chronic pyelonephritis]. PMID- 11785080 TI - [Surgical treatment of erectile dysfunction in Peyronie's disease]. AB - Methods of surgical treatment of fibroplastic induration of the penis are briefly reviewed. Supplements to classification of Peyronie's disease are proposed regarding the degree of erectile dysfunction and the angle of the penis deformity in erection. The authors analyse the results of operations performed from 1987 to 2000: Nesbit's operation (n = 13), intracavernous penis prosthesis (n = 48), dissection of the fibrous plaque, the defect repair with preserved dura mater followed by intracavernous prosthesis (n = 10). Indications for various surgical procedures in Peyronie's disease are described. PMID- 11785082 TI - [Secondary obstructive megaureter with detrusor-sphincter dyssynergia in children]. AB - 29 boys with secondary obstructive megaureter due to detruzor-sphincter dyssinergy were treated in 1989-1998. To normalize detruzor-sphincter relations, transurethral sphincterotomy was made in 25 boys. Later, 16 of them underwent autocatheterization of the urinary bladder and received alpha-adrenoblockers. Reconstructive plastic operations were performed in 34.5% (secondary megaureter of the degree III-IV). The author thinks more valid not to use the term "secondary obstructive megaureter" but to integrate this compound urinary tract lesion (megaureter with dyssinergy associated with diffuse dysplastic changes in the kidneys) into one syndrome. In secondary megaureter, longitudinal ureteral modelling is valid as this facilitates its reimplantation. Urodynamic examinations of the lower urinary tracts showed that sphincterotomy reestablished micturition in many cases, though high miction and intraabdominal pressure in dysadaptation of detruzor evidences for the existence of detruzor-sphincter dyscoordination in latent denervation of the urinary bladder. PMID- 11785081 TI - [Endoscopic treatment of bladder diverticula]. AB - Transurethral endoscopic incision of the urinary bladder's diverticular neck has been performed in 29 patients aged 44 to 90 years (mean age 65 years). 25(86.2%) patients had verified concomitant diseases and high anesthesia risk prohibiting radical surgery. According to preoperative diagnosis, the volume of the diverticula ranged from 20 to 700 ml, the diameter of the neck--from 0.3 to 2.0 cm. 10 patients had multiple diverticula. Uroflowmetry registered the maximal urinary flow rate (Qmax) within 2.1-5.3 ml/s. In all the patients surgery was performed under epidural anesthesia, simaltaneously with transurethral resection (TUR) of benign prostatic hyperplasia in 18 patients, with TUR of the urinary bladder neck or incision of the prostate because of its sclerosis in 11 patients. In 2 cases there was also TUR of the bladder for papillary cancer involving the bladder wall and the diverticulum, in 6 cases one-stage pneumatic or mechanical cystolithotripsy was performed. No intraoperative complications occurred. After the operation all the patients resumed normal micturition. Control examination after 6-48-month follow-up Qmax rose to 14.1-23.0 ml/s. Neither ultrasound investigation nor cystography detected diverticulum in 13 patients. The size of the diverticulum diminished in size in 16 patients. Residual urine in large diverticula (14 patients) was 50 ml maximum. 12 months after the operation 1 patient developed recurrent sclerosis of the prostate with reappearance of residual urine. He was reoperated (TUR of the prostate) without incision of the neck of the diverticulum. Postoperative complications were the following: mild electric burn of the thigh (1 case), acute epididimitis treated conservatively (1 case) and early postoperative bleeding which required endoscopic revision of the bladder and coagulation of the bleeding vessel from the cut neck of the diverticulum (1 case). Thus, transurethral incision of the bladder's diverticular neck is effective and low-traumatic intervention which in patients with severe somatic pathology is an alternative to the open surgery, while in patients without such pathology it does not complicate open operation (diverticulectomy) if it becomes necessary. PMID- 11785083 TI - [Present-day possibilities of prostate cancer screening in patients with benign prostatic hyperplasia before and after surgical treatment]. PMID- 11785084 TI - [Diagnostic role of interleukin-8 determination in chronic prostatitis]. AB - Measurements were made of interleukine-8 (IL-8) levels in ejaculate, prostatic secretion, blood serum of 60 patients with latent chronic prostatitis (CP). These levels were higher in CP patients than in healthy subjects. A rise in concentrations of IL-8 in prostatic secretion and ejaculate correlates with other inflammation markers. This may indicate the degree of CP activity. No relationship between IL-8 levels in ejaculate and prostatic secretion, and large dispersion of this marker allow using this criterion for diagnosis in combination with other indices of local immunity. PMID- 11785085 TI - [Comparative analysis of various techniques of prostatic drainage in patients with chronic obstructive prostatitis]. AB - The efficacy of prostatic drainage using transurethral vacuum aspiration (Introl 4 unit) and transrectal pneumovibromassage (PVM-R-01) was compared in 1511 patients with chronic obstructive prostatitis. The drainage was accompanied by local (urethral, rectal and urethral-rectal tripsin or chimotripsin electrophoresis) or systemic enzymic therapy (vobenzim). The highest effect of the drainage was achieved in patients pretreated for 5-7 days with systemic enzymes. Transrectal pneumovibromassage proved more effective and safe but the transurethral technique if indicated can be also used in the combined treatment. PMID- 11785086 TI - [Early hemodynamic changes in chronic obstructive pulmonary disease with initial respiratory failure]. AB - The chronic hypoxemia seems to play an important role in the pathogenesis of hemodynamic disorders in chronic obstructive pulmonary disease (COPD). The aim of the study was to follow-up the changes in pulmonary hemodynamics in COPD with mild respiratory failure. 78 COPD patients with Ist and IId degree of respiratory failure were investigated. The following investigations were carried out: two- dimensional echocardiography, spirometry, arterial blood gases and acid-base balance. In 18 of COPD patients a right heart catheterization was performed and the following indices were determined: mean pulmonary arterial (PA) pressure, pulmo-capillary resistance, teledyastolic right ventricular volume. The echocardiography showed significantly higher mean PA pressure values, an initial right ventricular dilatation and right ventricular wall hypertrophy. The indices of right heart catheterization were changed, too. The pulmo-capillary resistance was significantly increased. It was the most sensitive early parameter. The mean PA pressure was increased. There was no significant difference between the mean PA pressure determined by echocardiography and by right ventricular catheterization. A relationship between the degree of hypoxemia and the hemodynamic changes was found. The long development of COPD with mild respiratory failure leads to disorders in lung microcirculation and early changes in pulmonary hemodynamics. This process worsens the prognosis of COPD and the early prevention in the complex therapy of the disease is necessary. PMID- 11785087 TI - [Intermediate substrates in different stages of compensation of diabetes mellitus]. AB - In this research there were studied the changes in the concentrations of pyruvate, lactic acid, maleate, beta-oxybutyric acid oxyacetyc acid, blood fats, triglycerides, cholesterol blood lipoproteins in patients in different stages of compensation of diabetes mellitus. Studied were 44 patients during ablatio retinae during latentive diabetes, 16 patients with decompensated, 12 with subcompensated, and 8 with compensated diabetes. The average age of the studied patients was 54 years. The control group of 35 healthy people was of average age 52 years. All the groups show decreasing of the blood maleat. In the group of decompensated diabetes decreasing of keto-bodies, piruvat acid and lipid fractions was present. These factors were normalized, when diabetes was compensated. In this study, the diagnostic value of the investigation metabolites for compensation of diabetes mellitus is discussed. PMID- 11785088 TI - [Prostate-specific antigen (PSA) in women]. AB - Prostate-specific antigen (PSA) is a serine protease with chymotrypsin-like enzymatic activity. In males PSA is produced by the prostatic gland and it is present in prostatic tissue, seminal plasma and male serum. Initially, PSA was believed to be absent from all female tissues and fluids. However PSA has been detected recently in some female tissues (including breast, ovarian and endometrial tissues) and body fluids (serum, milk, amniotic fluid). The presence of PSA in these female tissues seems to be closely associated with steroid hormone regulation, especially androgens and progestins. Estrogen by itself seems to have no effect on PSA regulation, but it can impair androgen induced PSA production. In the tissues and fluids examined PSA is found in two molecular forms: free PSA is the enzymatically active form and in a complexed form bound to protease inhibitors. The data presented suggest that PSA can no longer be regarded as a specific prostatic marker, but as a protein that could be produced by cells bearing steroid hormone receptors under conditions of steroid hormone stimulation. Its biological role is not fully clarified, but PSA may be a candidate growth factor in normal tissues, pregnancy and tumors. At this point, PSA shows promise of being routinely used as a favorable prognostic indicator in female breast cancer. PMID- 11785089 TI - [Pulmonary surfactant system]. AB - The lung surfactant system (LSS) has a complex morphological and biochemical structure. LSS contains two components: cellular and non-cellular. The cellular component comprises three types of alveolar epithelium cells (type I, II, and II pneumocytes), alveolar macrophages (AM) and Clara bronchiolar cells. The non cellular component consists of alveolar surfactant (AS), hypo(epi)phase and alveolar epithelium cell glycocalix. AS represents phospholipids, proteins and carbohydrates mono-molecular layer. AM lamellar bodies (LB) and tubular myelin (TM) are disposed in the hypophase. LB and TM represent the depot-forms of lung surfactant (LS). Lung surfactant (LS) has a complex biochemical structure and comprise the following components: phospholipids, neutral lipids, glycolipids, surfactant-specific proteins, plasmaproteins, enzymes, carbohydrates and aminoacids. LS is synthesized in type II pneumocytes and Clara cells. LS catabolism is mainly effected by AM. The LSS has a fundamental role in the physiological functions of lungs. Through its antiatelectatic and antioedematic functions, LSS sustains the basic physiological functions of lungs--alveolar ventilation and gas diffusion through the alveolar-capillary wall. Besides this, LSS performs several protecting functions--antioxidant defense, non-specific defense mechanisms, immunodulatory action, cytotoxicity agents metabolism and others. The injury of the structure and functions of LSS is an important pathogenic mechanism in the pathogenesis of different lung diseases. Practically, a pathological process in lungs, which is not related to changes in LSS structure and functions, does not exist. Recently developed surfactant replacement therapy with natural and synthetic surfactants has an important place in the therapy of several lung diseases. PMID- 11785090 TI - [Anticancer activities of N.N Petrov (on the 125th anniversary of his birth)]. PMID- 11785091 TI - [Demographic, social and medical problems of the aging population]. PMID- 11785093 TI - [Diagnosis and differential diagnosis of chronic myeloid leukemia]. PMID- 11785092 TI - [Diagnosis of recurrences of bladder cancer]. PMID- 11785094 TI - [Role of monokines in neoplastic and normal tissue reactions to local irradiation]. PMID- 11785096 TI - [Morbidity of cervical and uterine cancer in the Republic of Armenia]. PMID- 11785095 TI - [Prospects for using aromatase inhibitors in treating endometrial cancer patients]. PMID- 11785097 TI - [Comparative analysis of data from trepanobiopsy and radionuclide visualization of bone marrow]. AB - Scintigraphy of the bone marrow was tested as a noninvasive procedure of hemopoiesis evaluation in 79 cancer patients. Scintigraphy and trepanobiopsy of the marrow of iliac bones were carried out in all patients. The results matched in 88.6% (70 out of 79) pointing to a significant correlation (p < 0.01). A similar correlation (p < 0.05) (80% matching) was observed in cases of irradiation of ilioinguinal nodes. Besides, the coefficient of correlation of the data of quantitative and semiquantitative analysis of marrow scintigraphs was 0.7725 (p < 0.01). To summarize, the significant correlation between the findings of scintigraphic and morphological examination pointed to the potential of the former as an noninvasive procedure for evaluation of hemopoiesis. PMID- 11785098 TI - [Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. AB - Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration. PMID- 11785099 TI - [Peroxidase activity in human uterine tissue: connection with clinico morphological features of endometrial cancer]. AB - Peroxidase activity was determined in 98 patients with endometrial cancers. In 34 patients with endometrial cancers, the activity of the enzyme was also detected in the neighbouring unchanged (normal) tissues. It was shown that in tumor tissues the level of peroxidase activity was higher than in normal ones. The peroxidase activity increased both in tumor and normal endometrium when clinical and morphological characteristics of tumor were unfavourable, i.e. at later stages of the disease, deeper invasion to myometrium, lower levels of differentiation of tumors. The peroxidase activity was somewhat higher in post menopausal women; however, no direct was found between the activity of this enzyme in malignant and normal tissues, on the one hand, and the menstrual status of patients with different clinical and morphological characteristics of endometrial cancer, on the other relationship. The level of peroxidase activity in normal and malignant tissues was more pronounced in advanced and poorly differentiated tumors. It seems important to use peroxidase activity as a prognostic factor and as a possible marker of endometrial cancer hormone dependence that needs further investigation. PMID- 11785100 TI - [Efficacy of computer tomography in locally disseminated non small cell lung cancer]. AB - The results of computed tomography (CT) staging and surgical data have been compared to assess the former in diagnosing localized lung cancer. The study included 79 patients with locally advanced non-small cell lung cancer who had been treated by surgery. Local invasion was adequately diagnosed by CT in 67 (84.8%) and primary tumor stage--51.9%; overdiagnosis--15.2% and underdiagnosis- 32.9%. The CT and final diagnosis findings on lymphogenous dissemination matched in 64.6%; overdiagnosis--16.5% and underdiagnosis--18.9%. Sensitivity, specificity and diagnostic accuracy in identifying stage T3 and T4 tumors were 62.3, 65.4 and 63.3%, respectively; lymphogenous dissemination--76.9, 64.9 and 74.7%, respectively. PMID- 11785101 TI - [The problem of histological nomenclature and classification of carcinogenesis stages in the breast]. AB - Objective diagnostic criteria for carcinogenesis staging and classification are suggested on the basis of a ploidometric investigation of 15,000 nuclei of cells of lobular and ductal epithelial neoplasms of the breast. Differential diagnosis is to apply to the following stages of mammary carcinogenesis: (a) signs of epithelial hyperplasia (/0) and intraepithelial neoplasia stage I (benign stages- /1); (b) intraepithelial neoplasia stage II (border-line stages--/2); (c) infiltrating carcinoma with or without metastases (malignant stages--/3). PMID- 11785102 TI - [Activity of cathepsin H in blood and biopsies of patients with precancerous conditions and mouth cancer]. AB - The paper discusses the results of an investigation of cysteine cathepsin H levels in preneoplastic lesions and tumors of the oral cavity as measured in tissue bioptates and blood plasma. Changes in the levels at different stages have been followed and relevant differences in different groups of patients established. PMID- 11785103 TI - [Role of the antioxidant system and redox-dependent regulation of transcription factors bcl-2 and p53 in forming resistance of human K562 erythroleukemia cells to doxorubicin]. AB - Prooxidant effect of chemotherapeutic agents is of significant interest in connection with activation of oxidative stress in cancer cells. Role of development of adaptive antioxidant response to the rise of resistance to cytotoxical effect of doxorubicin (DOX) has been studied in human erythroleukemia K562 cells. Growth of resistance to DOX caused enhancement of antioxidant enzymes (Cu, Zn-SOD, Mn-SOD, catalase) elevation of Mn-SOD activity being predominant. Additional increasing of antioxidant level was elevation of GSH maintenance and level of GST-related enzymes (glutathione peroxidase, glutathione S-transferase, glutathione reductase) in resistance K562/DOX cells. The enhancement of antioxidant system prevented activation of lipid peroxidation. Furthermore, the antioxidant growth caused decrease of level of proteintyrosine kinases, thioredoxin, thioredoxin reductase in contrary to elevation of glutaredoxin activity. Increasing of Bcl-2 and suppression of p53 levels was found to be caused by the change of redox state of K562DOX cells. The data support the suggestion that adaptive antioxidant response to prooxidant effect of DOX promotes the development of cellular drug resistance. PMID- 11785104 TI - [Effect of vilon and epithalone on induction and growth of induced bladder neoplasms in rats]. AB - Experimental data on the effect of peptides--Vilon (Lys-Glu) and Epitalon (Ala Glu-Asp-Gly)--on induction of urinary bladder tumors in rats are presented. Treatment with Vilon was followed by a significant fall in tumor incidence in 56% of experimental animals, as compared with 75.5% in control, as well as inhibition of early-onset neoplastic changes in the bladder mucosa. No inhibitory effect of Epitalon was recorded. PMID- 11785105 TI - [Disruption of circadian rhythms of biogenic amines in rat hypothalamus upon administration of 1,2-dimethylhydrazine]. AB - Levels of norepinephrine (NE), dopamine (DA) and the main metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) have been measured in the suprachiasmatic nuclei (SCN), preoptic area (PA), and median eminence (ME) of hypothalamus of rats after sole subcutaneous injection of 1,2-dimethylhydrazine (SDMH). Circadian changes of DA in all the brain structures under study as well as of NE in PA were observed in the control group, their levels in the mornings being higher than in the evenings; a circadian change of 5-HIAA in SCN had an opposite tendency. Both the evening (11 p.m.) and morning (11 a.m.) administrations of SDMH at the dose of 21 mg/kg body weight resulted in disturbances of all the circadian rhythms observed in control. In some cases only a 12 hrs circadian rhythms phase shift was found, in the others these rhythms of neurotransmitters disappeared entirely. The evening administration of SDMH, unlike the morning one, resulted in an increase in total NE content in the hypothalamic structures under study. It is suggested that the effect of SDMH on the levels and circadian rhythms of neurotransmitters in the hypothalamic structures under study is due to affecting activities of the enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis and secretion rhythms, as well as to its genotoxic influence upon the genes controlling circadian actions. PMID- 11785106 TI - [Tumor growth index as an integral criterion for the efficacy of antineoplastic therapy under experimental conditions]. AB - An additional criterion is suggested for description of effectiveness of therapy of experimental tumors--tumor growth index. It is a ratio of area covered by the kinetic curve of tumor growth in the study group and that in control. The index is intended to describe the efficacy of therapy in terms of degree and duration of the effect. PMID- 11785107 TI - [Activity of proteolytic enzymes and their inhibitors during proliferation of P 815 mastocytoma cell proliferation in vitro]. AB - Proliferation of mastocytoma P-815 cells in vitro was accompanied by a rise in cathepsin D, elastase- and trypsin-like proteinase activity during 6 hours of culturing and a decline by hour 24. Yet alpha 1-proteinase inhibitor activity was inversely proportional to proteinase concentration. Antiproliferative action of actinomycin D disrupted phase variation of proteinase activity and, consequently, the level of alpha 1-proteinase inhibitor rose after 6 hours of cell culturing while that of alpha 2-macroglobulin--after 48 hr. Antiproliferative effect of actinomycin D was eliminated by reduced inhibitor level brought about under the influence of exogenous trypsin. When trypsin was added cathepsin D activity reached its peak 6 hr later while that of alpha 1-proteinase inhibitor declined. That effect and the actomycin D-proteinase inhibitor mechanism were retained when trypsin and actomycin D were present together. It is suggested that cathepsin D and alpha 1-proteinase inhibitor activity plays a key role in realizing the proliferative potential of mastocytoma P-815 cells. PMID- 11785108 TI - [Organ-conserving operations in treatment of breast cancer]. AB - The report deals with the results of conservative surgery carried out in 261 patients with breast tumors T1-2N0-1M0. Special procedure was employed to assess edges of removed segments of tumor tissue in 46. A classification of edge condition is offered. It was found that degree of intervention should depend on whether tumor segments are left in the edge. The end results were evaluated on the basis of tumor dissemination to the regional lymph nodes, survival duration and frequency of locally-advanced relapse. Five-year survival was 91.4%; localized recurrence incidence--3.8%. PMID- 11785109 TI - [Secondary tumors in Hodgkin's disease patients]. AB - A study is presented of second malignancies detected after treatment for Hodgkin's disease in 942 patients treated at the Institute's Clinic (1973-1993). Solid tumors were diagnosed, generally, during long complete remission, both after chemoradiation or radiotherapy (2.2 and 1.3%, respectively, p > 0.1). Yet, second tumor incidence tended to increase after combination treatment. Intestinal tumors were the most frequent. Tumors did not arise necessarily at sites which had been irradiated. Total doses absorbed by involved organs varied from 4-7 to 24-44 Gy, thus implying that absolute values of such doses did not correlate directly with risk of solid tumor development; the same was true for size of exposure fields. Dose distribution in time is of particular interest: there were no tumors among those treated with accelerated multifractionated irradiation. If radiotherapy procedures are improved and individual schedules of fractionated irradiation are used, the probability of solid tumor incidence, which, after radiotherapy of Hodgkin's disease, is not very high, can be still lowered. PMID- 11785110 TI - [Intraoperative radiotherapy in the combined treatment of stomach cancer. Methodological and technical aspects]. AB - Theoretical, experimental and clinical rationale is discussed for selection of targets and main parameters of intraoperative radiotherapy for gastric cancer. Topometric and dosage research has been carried out. Original technological equipment has been developed for safe treatment using the domestic accelerator Mikrotron-M. Procedures for continuous relay pre- and intraoperative radiotherapy of gastric tumors in conjunction with radical surgery have been devised and adapted to operation of a specialized clinical facility. PMID- 11785111 TI - [Results of clinical studies of the efficacy of intraoperative radiotherapy in combined treatment of stomach cancer]. AB - The results of clinical application of an original method of operable gastric cancer treatment including pre- and intraoperative irradiation (IORT) and radical intervention are presented. According to a randomized study, combination treatment did not involve intra- and postoperative complication rates higher than those of surgery alone. Moreover, a significant decrease in postoperative pancreatitis was registered. IORT is a highly effective method of adjuvant treatment of operable gastric cancer. Due to its application in conjunction with preoperative irradiation and radical surgery, the end results of locally-advanced gastric cancer improved. PMID- 11785112 TI - [Gene therapy of tumors, state of the art and prospects]. AB - Gene therapy entered the clinical arena more than one decade ago. Hundreds of clinical trials were initiated worldwide to investigate many different approaches to oncological problems. Positive results became available only recently, showing that gene therapy is actually capable of curing human neoplasms. This editorial scrutinizes the whole field of gene therapy for cancer, describing advantages and disadvantages of the various approaches, and trying to forecast the main future developments. PMID- 11785113 TI - [Pathological factors involved in lymph node status determination in colorectal carcinoma: analysis of 166 cases with long-term follow-up]. AB - Lymph node status has great clinical importance in the management of patients with colorectal cancer. Several pathologic factors may affect the accuracy of nodal status assessment in this tumor type. The aim of the present study was to evaluate, in a series of 166 stage II and stage III colorectal adenocarcinomas, the following pathologic parameters: number of lymph nodes recovered and examined, number of lymph nodes with metastases, and number of tumor nodules (TNs) in the perirectal or pericolic adipose tissue greater or smaller than 3 mm in diameter (TNs > 3 mm and TNs < 3 mm, respectively). The prognostic significance of these parameters, as well as of other histopathologic variables, was determined using univariate and multivariate survival analyses. Our results indicate that the examination of a small number of regional lymph nodes may result in understaging of tumors classified as pN0 (stage II). In addition, our data suggest that TNs > 3 mm and TNs < 3 mm represent distinct pathologic entities. TNs > 3 mm should be considered the prognostic equivalent of lymph node metastases as recommended by the 1997 TNM classification. In contrast, TNs < 3 mm probably originate by intravascular or perivascular tumor extension. Their presence is associated with adverse clinical outcome in stage III patients, regardless of the number of lymph node metastases. PMID- 11785114 TI - [CK20 expression in the gastrointestinal tract of the embryo and fetus]. AB - A novel type of cytokeratin, cytokeratin 20 (CK20), was added in 1990 to the classic catalog of human cytokeratins, a heterogeneous group of proteins present in almost all epithelia. In man, the expression of CK20 is almost entirely confined to the gastro-intestinal epithelium, to the urothelium and to Merkel cells. Since only few data are available regarding the expression of CK20 in the developing human intestinal mucosa, we studied CK20 immunoreactivity in fetal and neonatal human gut. Immunoreactivity for CK20 was tested in fetuses and newborns, from the twelfth up to the fortieth week of gestation. In each subject, a specimen from the oesophagus, stomach, small intestine, colon, appendix was studied. Tissue samples were routinely processed and paraffin sections were stained with the CK20-specific antibody IT-Ks 20.8. CK20 immunoreactivity was absent in the oesophageal epithelium and it was unevenly distributed in the gastrointestinal mucosa. Three main patterns of immunoreactivity were observed during normal development: the first, found in the stomach and in the small bowel, is characterized by a progressive increase in CK20 expression during gestation; the second pattern, found in the duodenum, shows a progressive decrease in CK20 expression during gestation; in colon and appendix (third pattern), we did not find significant changes in the degree of immunoreactivity for CK20 during gestation. CK20 is unevenly expressed in developing human intestinal mucosa. The degree of positivity for CK20 appears to be related to the epithelial maturation stage only in gastric and small bowel mucosa. Further studies are needed to verify if the uneven CK20 immunoreactivity in the gastrointestinal tract persists even in adulthood. PMID- 11785115 TI - [ASCUS in screening]. AB - The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening. The prevalence of ASCUS by patient age has seldom been investigated. The present paper reports the prevalence of ASCUS in a large series of screening Pap smears from the Italian region of Emilia-Romagna. The study was based on the data collected by the Department of Health of the Emilia-Romagna Region for the first 3-year round (1997-1999) of a population-based screening programme (target age, 25-64 years). The age-specific frequency of ASCUS has been calculated as a prevalence rate per 1000 screened patients. A total of 597,386 women participated in the programme. Women diagnosed with ASCUS (n = 8205 or 13.7 per 1000) accounted for 49% of the recalls for colposcopy (n = 16,871, or 28.2 per 1000). The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years. The prevalence of ASCUS peaked at age 45-49 years (17.3 per 1000 subjects). The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy. PMID- 11785116 TI - [The Pap test in HIV-positive women]. AB - The aim of this work was to estimate the frequency of abnormal Papanicolau (Pap) smears in a group of HIV-infected women undergoing cervical screening. We re examined 162 Pap smears from 118 patients infected with HIV. The patients were aged 23-55 years. A total of 108 smears (66.6%) from 80 patients were negative; 14 smears (8.6%) from 14 patients showed inflammation; 3 smears (1.8%) from 3 patients had atypical squamous cells of undetermined significance (ASCUS); 20 smears (13.5%) from 16 patients were abnormal for human papillomavirus (HPV); 13 smears (8.0%) from 9 patients revealed low-grade, squamous intraepithelial lesions; 10 smears (6.2%) from 7 patients were SIL-HG; the diagnosis of carcinoma was made in 3 cases (1.8%) and 2 smears from 2 patients were unsatisfactory. HIV infected women have an increased rate of abnormal Pap smears for both HPV infections and cervical dysplasia. These results confirm the validity of cervical screening by Pap test. PMID- 11785117 TI - Carl von Rokitansky and the Italian translation of the Handbuch der Pathologischen Anatomie: a linguistic and doctrinal enigma. AB - Carl von Rokitansky was the author of a treatise that came out between 1842 and 1846 with the title Handbuch der Pathologischen Anatomie. A historical milestone in pathological anatomy, Rokitansky's work represented the first attempt to systematically classify pathological specimens. Its publication inevitably made a great impact on Vienna, at that time the major European medical centre. The Italian translation of Rokitansky's masterpiece, Trattato Completo di Anatomia Patologica, published in Venice in 1852, was carried out by Ricchetti and Fano: the former a philologist and the latter a Triestine physician who, in 1873, had worked at Simon Pertot's side, the first prosector to be assumed in Trieste. From the start, the two translators not only made no secret of the linguistic obstacles they came up against, but also how unconvincing Rokitansky's doctrines were; a scepticism emerged from their words that inevitably contributed to the realization of a translation difficult to read. Undoubtedly, Rokitansky elaborated a theory of disease containing a certain degree of unclarity and in this respect it is interesting to emphasize that even the English translation, Manual of Pathologic Anatomy (1849-1854), demonstrated similar conceptual problems. A convinced supporter of gross pathology, Rokitansky put forth a theory of disease, the so-called Krasenlehre, resting upon humoral doctrines. This new knowledge inevitably exerted a great influence over Viennese, as well as German, medicine. Rokitansky's humoral pathology survived until the 1850s, when it was attacked by young Virchow, the future, universally recognized, father of cellular pathology, who definitively extinguished speculative humoral pathology. PMID- 11785118 TI - [Myoepithelial differentiation markers in salivary gland neoplasia]. AB - Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation. PMID- 11785119 TI - [Parosteal rib lipoma: description of a case]. AB - Parosteal lipoma is a usually indolent, rare benign tumor, characterized by clinicopathological findings similar to those of the commonly occurring subcutaneous lipoma, except for its intimate relationship with the connective tissue of the subjacent periosteal region. Parosteal lipoma commonly affects the diaphysis of long bones of the upper and lower limbs. We report an exceedingly rare case of parosteal lipoma of the rib, which presented in a 59-year-old man experiencing previous multiple traumas in this site. PMID- 11785120 TI - [Fallopian tube adenocarcinoma: synchronous neoplasia and severe uterine endocervical squamous epithelial dysplasia]. AB - We report a rare case of primary carcinoma of the fallopian tube. A 72-year-old post-menopausal woman presenting with abnormal secretion of blood-stained liquid, underwent surgery because of findings of atypical squamous cells (ASCUS) on a routine Papanicolaou smear. The histological diagnosis on cervical biopsy was of CIN 3. Adenocarcinoma of the Fallopian tube was incidentally found. PMID- 11785121 TI - [Glycogen-rich clear-cell breast carcinoma with neuroendocrine differentiation features]. AB - Glycogen-rich, clear cell carcinoma of the breast (GCC) is a rare type of breast cancer. Histological features are usually those of ductal carcinoma, but cases featuring lobular, tubular, and mixed ductal-tubular carcinoma have been reported. The presence of "numerous cells with clear cytoplasm" has been reported in some cases of primary neuro-endocrine tumors of the breast. Moreover, no case of GCC of the breast with neuro-endocrine features has been described. We report a case of 33-year-old woman with a palpable lump of the right breast. Fresh tissue obtained from the operating theatre was fixed in 10% formalin and routinely processed to paraffin. Serial sections were stained with haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and PAS following diastase digestion (PASd); other sections were processed for immunohistological detection of chromogranin, synaptophysin, vimentin and smooth muscle actin. For electron microscopy, the tissue was fixed in 2.5% glutaraldehyde in cacodylate buffer. The samples were post-fixed in osmium, dehydrated in ethanol and embedded in araldite. Thin sections, counterstained in uranyl acetate and lead citrate, were studied under a Philips 400T electron microscope. The lump at histological examination was entirely composed of optically clear, neoplastic cells. The cytoplasm was filled with numerous PAS-positive granules which did not stain after the diastase digestion, leading to a diagnosis of GCC of the breast. Some histological (i.e. pattern of growth, blunt edges of neoplastic glands and numerous vessels) and cytological features (i.e. nuclear monomorphism and fine chromatin) prompted us to investigate the possible neuro-endocrine differentiation of the lesion. Immunohistochemical and ultrastructural studies strongly support such hypothesis. To the best of our knowledge, we report the first case of GCC of the breast with neuro-endocrine features. PMID- 11785123 TI - [A new scenario for cutaneous melanoma staging (the new TNM classification)]. PMID- 11785122 TI - [Bronchiolitis obliterans-organizing pneumonia (BOOP) containing asbestos bodies: clinico-pathological study of a case]. AB - We describe a case of bronchiolitis obliterans-organizing pneumonia (BOOP) with asbestos bodies. A 65-year-old man, treated in the past for gastric lymphoma and with an history of asbestos exposure, presented with fever and two nodular opacities in the lower lobe of the left lung. Histologic examination revealed a BOOP pattern; in the inflammatory tissue some asbestos bodies were present. Patients exposed to asbestos may rarely present with localized inflammatory pulmonary lesions. In these cases, the possible etiopathogenetic role of asbestos needs further studies. PMID- 11785124 TI - A practical approach to bladder sampling and diagnostic reporting of pathological findings. AB - The most common bladder specimens are obtained from endoscopic biopsies and transurethral resections (TURB), both of which sample subepithelial tissue of varying depth. Other specimens can be obtained from cystectomy, cystoprostatectomy, pelvic exenteration ("en bloc" resection), and partial cystectomy including resection of diverticulae and surgical excision of a urachal carcinoma. The correct assessment of bladder specimens may provide clinically relevant diagnostic and prognostic data. This protocol is intended to assist pathologists in providing clinically useful information as a result of examination of surgical specimens. PMID- 11785125 TI - [Joseph Babinski, Jerry Lewis...the print-driver of the human body]. PMID- 11785126 TI - [Einstein's god: the late revolution in microscopy...and other things]. PMID- 11785127 TI - [Re-reading from old to new the recipes for restoring freshness to mummified or desiccated tissues]. PMID- 11785128 TI - [Aerobic methylotroph bacteria as phytosymbionts]. AB - This paper deals with the physiological, biochemical, and molecular genetic aspects of the interaction of aerobic methylotrophic bacteria with plants by means of phytohormones (such as cytokinins and auxins) and other physiologically active substances (vitamins, exopolysaccharides, bioprotectants). The state of the art and the prospects of research in the field of bacteria-plant interactions and the application of aerobic methylotrophs in plant biotechnology is discussed. PMID- 11785129 TI - [Intracellular accumulation of monomer precursors of polyphosphates and polyhydroxyalkanoates from Acinetobacter calcoaceticus and Escherichia coli]. AB - The formation of polyhydroxyalkanoates granules in anaerobically grown Escherichia coli cells was found to be preceded by the intracellular accumulation of carbonic acids (predominantly, acetic acid), amounting to 9% of the cytosol. The intracellular concentration of acidic metabolites increased after the lyophilization of the bacterial biomass and decreased after its long-term storage (3.5-13.5 years). The decrease in the concentration of acidic metabolites is likely due to the dehydration of dimeric carbonic acids in the viscoelastic cytosol of resting bacterial cells. The hydrophobic obligately aerobic cells of Acinetobacter calcoaceticus IEGM 549 are able to utilize a wide range of growth substrates (from acetate and citrate to hydrophobic hydrocarbons), which is considerably wider than the range of the growth substrates of E. coli (predominantly, carbohydrates). The minimal essential and optimal concentrations of orthophosphates in the growth medium of A. calcoaceticus were found to be tens of times lower than in the case of E. coli. The intracellular content of orthophosphates in A. calcoaceticus cells reached 35-77% of the total phosphorus content (Ptotal), providing for the intense synthesis of polyphosphates. The Ptotal of the A. calcoaceticus cells grown in media with different proportions between the concentrations of acetate and phosphorus varied from 0.7 to 3.3%, averaging 2%. This value of Ptotal is about two times higher than that observed for fermenting E. coli cells. Lowering the cultivation temperature of A. calcoaceticus from 37-32 to 4 degrees C augmented the accumulation of orthophosphates in the cytoplasm, presumably owing to a decreased requirement of growth processes for orthophosphate. In this case, if the concentration of phosphates in the cultivation medium was low, they were completely depleted. PMID- 11785130 TI - [Autotrophic synthesis of polyalkanoates by Alcaligenes eutrophus in presence of carbon monoxide]. AB - The CO-resistant strain B5786 of the hydrogen-oxidizing bacterium Alcaligenes eutrophus was found to be able to synthesize polyhydroxyalkanoates (PHAs) under the conditions of growth limitation by nitrogen deficiency (the factor that promotes PHA synthesis) and growth inhibition by carbon monoxide. The gas mixtures that contained from 5 to 20 vol% CO did not inhibit the key enzymes of PHA synthesis--beta-ketothiolase, acetoacetyl-CoA reductase, hydroxybutyrate dehydrogenase, and PHA synthase. In the presence of CO, cells accumulated up to 70-75 wt% PHA (with respect to the dry biomass) without any noticeable increase in the consumption of the gas substrate. Chromatographic-mass spectrometric analysis showed that the PHA synthesized by A. eutrophus is a copolymer containing more than 99 mol% beta-hydroxybutyrate and trace amounts of beta hydroxyvalerate. The PHA synthesized under the conditions described did not differ from that synthesized by A. eutrophus cells from electrolytic hydrogen. PMID- 11785131 TI - [Effect of rib83 mutation on riboflavin biosynthesis and iron assimilation in Pichia guilliermondii]. AB - The monogenic rib83 mutation blocked riboflavin oversynthesis in the yeast Pichia guilliermondii and lowered iron acquisition by cells, their ferric reductase activity, and the growth rate in iron-deficient media. Mutants with the combined mutations of rib83 with rib80 and rib81 (the last two mutations impair the negative control of riboflavin synthesis and thus cause its oversynthesis) were unable to depress the enzymes of flavinogenesis (GTP cyclohydrolase and riboflavin synthase) and to overproduce riboflavin in both iron-deficient and iron-sufficient media. This suggests that the rib83 mutation is epistatic with respect to the rib80 and rib81 mutations. The RIB83 gene may positively control both riboflavin synthesis and iron acquisition in the yeast P. guilliermondii. PMID- 11785132 TI - [Effect of the media salinity on destruction of petroleum oils by nocardioform bacteria]. AB - Oil degradation by cultures of Rhodococcus erythropolis and Dietzia maris was found to depend on the NaCl concentration in the medium. Optimal utilization of turbine oil by R. erythropolis and D. maris was observed at 0.5 and 2 to 5% NaCl concentration, respectively. Mineral oil and a mixture of paraffins (C14-C18) were utilized within a broader range of the medium salinity. As shown by fluorescent microscopy, D. maris colonies formed on the oil drop surface, whereas R. erythropolis cells penetrated the drops. The strains studied may populate various ecological niches in oil-containing ecosystems. They are promising for the development of microbial preparations for cleaning the environment from oil pollution. PMID- 11785133 TI - [Ultrastructural organization of cytoplasmatic membrane of Anaerobacter polyendosporus studied by electron microscopic cryofractography]. AB - Anaerobacter polyendosporus cells do not have typical mesosomes. However, the analysis of this anaerobic multispore bacterium by electron microscopic cryofractography showed that its cytoplasmic membrane contains specific intramembrane structures in the form of flat lamellar inverted lipid membranes tenths of nanometers to several microns in size. It was found that these structures are located in the hydrophobic interior between the outer and inner leaflets of the cytoplasmic membrane and do not contain intramembrane particles that are commonly present on freeze-fracture replicas. The flat inverted lipid membranes were revealed in bacterial cells cultivated under normal growth conditions, indicating the existence of a complex-type compartmentalization in biological membranes, which manifests itself in the formation of intramembrane compartments having the appearance of vesicles and inverted lipid membranes. PMID- 11785134 TI - [Fine structure of mummified cells of microorganisms formed under exposure to a chemical analog of anabiosis autoinducer]. AB - Under the influence of alkyl hydroxybenzene (C6-AHB) added to cell suspensions at a concentration of (1-5) x 10(-3) M, the cells of Saccharomyces cerevisiae, Micrococcus luteus, and Thioalkalivibrio versutus underwent dramatic changes in the ultrastructural organization of cell membranes, cytoplasm, and inclusions. In yeast suspension, the first changes were observed after 15 min in the structure of slit-like invaginations in the cytoplasmic membrane (CM): they were shortened and thickened. In the subsequent 30 to 60 min, CM ruptures were formed in the regions devoid of intramembrane protein particles and in the slit-like invaginations. After 24 h, complete disintegration of the intracellular membrane structures and conglomeration of the ribosomal part of the cytoplasm occurred. Similar changes were observed on the exposure of gram-positive and gram-negative bacteria to AHB. However, the cell wall in all the microorganisms studied was not destroyed, and in Micrococcus luteus it was even thickened. These mummified forms were preserved as morphologically intact but nonviable cells for more than three years of observations. By their ultrastructural characteristics, these mummified forms of microorganisms were similar to the fossilized microorganisms discovered by us in fibrous kerite. The concept of micromummies was formulated. AHB are supposed to play an important role in the process of fossilization of microorganisms in nature. PMID- 11785135 TI - [Heterogeneity of nucleotide sequences of 16S ribosomal RNA genes from the Desulfotomaculum kuznetsovii type strain]. AB - Two copies of the 16S rRNA gene, rrnA and rrnB, of the type strain 17T of the thermophilic sulfate-reducing bacterium Desulfotomaculum kuznetsovii were cloned and completely sequenced. The comparison of the determined sequences revealed considerable heterogeneity (8.3%) of the two genes, rrnA and rrnB. The main differences were associated with superlong inserts located at the variable 5'- and 3'-terminal regions of the 16S rRNA genes. Comparative analysis that involved analogous genes from the phylogenetically closest representatives of the genus Desulfotomaculum showed that disregard of the heterogeneity of the two gene copies distorts the position of the bacterium studied in the phylogenetic tree. PMID- 11785137 TI - [Isolation and preliminary characterization of cryptic plasmids from Erwinia carotovora]. AB - Of the fifty-two Erwinia carotovora strains studied, sixteen were found to contain extrachromosomal DNA (plasmids) from 2.5 to 129 kbp in size. Some E. carotovora strains bore two to five different plasmids. Experiments showed that the cryptic plasmids of erwinia are not responsible for their resistance to antibiotics and are not involved in the synthesis of macromolecular colicin-like carotovoricins. At the same time, one of the E. carotovora strains, 13A, augmented the production of carotovoricin after curing from one of its plasmids, 47.7-kbp pCA 6-2. Three E. carotovora subsp. carotovora strains and one E. carotovora subsp. atroseptica strain contained large 129-kbp plasmids, which may play a role in the ecology of phytopathogenic pectinolytic erwinia. PMID- 11785136 TI - [Stability of recombinant plasmids in transgenic microorganism cells under various environmental conditions]. AB - The copy number of R plasmids weakly depends on the selective pressure of the respective antibiotic but does depend on the physiology of the host species and the type of plasmids and cloned genes, whose expression leads to a further load on the biosynthetic apparatus of cells. The last factor is critical in the maintenance of recombinant plasmids in transgenic microorganisms. PMID- 11785138 TI - [Characteristics of Bacillus cereus dissociants]. AB - The autoregulation of the phenotypic (populational) variability of the Bacillus cereus strain 504 was studied. The isolated colonial morphotypes of this bacterium were found to differ in their growth characteristics and the synthesis of extracellular proteases. The phenotypic variabilities of vegetative proliferating cells and those germinated from endospores and cystlike refractory cells were different. Bacterial variants also differed in the production of the d1 and d2 factors (the autoinducers of dormancy and autolysis, respectively) and sensitivity to them. The possible role of these factors in the dissociation of microorganisms is discussed. PMID- 11785139 TI - [Effect of chitosan oligomer on phage particles and reproduction of phage 1-97A in Bacillus thuringiensis culture]. AB - The causes of bacteriophage 1-97A inactivation by the chitosan oligomer with a polymerization degree of 15 and the influence of the oligomer on the phage reproduction in the culture of Bacillus thuringiensis subsp. galleriae, strain 1 97, were studied. The study of the inactivation kinetics showed that, in 1 h, virtually all chitosan was bound to the phage particles, causing, as evidenced by electron microscopy, DNA release from the phage head, destruction of the phage particles, and agglutination of the phage particles or of their tails in the region of the endplate. High-polymeric chitosan caused more pronounced destruction of the phage particles than the oligomer. It was established that chitosan prevented the production of complete phage particles. One of the mechanisms of such an influence may be the production in the presence of chitosan of phage particles devoid of DNA. PMID- 11785140 TI - [Amphibacillus fermentum sp. nov., Amphibacillus tropicus sp. nov.--new alkaliphilic, facultatively anaerobic, saccharolytic Bacilli from Lake Magadi]. AB - New alkaliphilic, saccharolytic, rod-shaped, gram-positive bacteria resistant to heating and drying and phylogenetically affiliated to the Bacillus lineage were isolated under strictly anaerobic conditions from sediments of the alkaline and highly mineralized Lake Magadi. Strain Z-7792 forms endospores; in strain Z-7984, endospore formation was not revealed. The strains are capable of both anaerobic growth (at the expense of fermentation of glucose and certain mono- and disaccharides with the formation of formate, ethanol, and acetate) and aerobic growth. Among polysaccharides, the strains hydrolyze starch, glycogen, and xylan. Yeast extract or methionine are required for growth. The strains are strict alkaliphiles exhibiting obligate requirement for Na+ and carbonate ions but not for Cl- ion. Growth occurs at a total mineralization as high as 3.3-3.6 M Na+, with an optimum at 1-1.7 M Na+. Strain Z-7792 is an obligate alkaliphile with a pH growth range of 8.5-11.5 and an optimum of 9.5-9.7. Strain Z-7984 grows in a pH range of 7.0-10.5 with an optimum at 8.0-9.5. Both strains are mesophiles having a growth optimum at 37-38 degrees C. They belong to bacilli with a low G + C content. The G + C contents of the DNA of strains Z-7792 and Z-7984 are 39.2 and 41.5 mol%, respectively. These isolates of facultatively anaerobic, strictly alkaliphilic, Na(+)-dependent bacilli can be considered representatives of the ecological group adapted to the life at drying-up shoars of soda lakes. Because of their independence of NaCl and lack of obligate dependence on sodium carbonates, the isolates are to be assigned to athalassophilic organisms. According to their physiological and phylogenetic characteristics, they taxonomically belong to group 1 of the species of bacilli, occupying a position intermediate between the genera Amphibacillus and Gracilibacillus. The isolates are described as new species of Amphibacillus: A. fermentum (type strain, Z 7984T) and A. tropicus (type strain, Z-7792T). PMID- 11785141 TI - [Microbiological characterization of the accreted ice of subglacial Lake Vostok, Antarctica]. AB - The accreted ice of subglacial Lake Vostok extends upward from the lake water level (a depth of 3750 m) to the bottom surface of the overlying Antarctic ice sheet. All of the accreted ice samples, taken from depths between 3541 and 3611 m, were found to contain pro- and eukaryotic microorganisms, whose number and diversity varied in different ice horizons and correlated, to a certain degree, with the occurrence of organic and inorganic impurities in a given horizon. Some biological objects found in the accreted lake ice, including bacteria, microalgae, and the pollen of higher plants, were morphologically similar to those found earlier in the glacier ice bulk. The others were not. It is suggested that the microorganisms found in the lake ice may come from different locations- the bottom layer of the glacier ice, the bedrock underlying the glacier, and the lake water. PMID- 11785142 TI - [Bacterial diversity in microcosms of soils with various humidity]. AB - The succession analysis of bacterial diversity in the A horizons (rich in organic matter) of three contrasting types of soil--burozem, soddy gley soil, and chernozem--showed that the bacterial diversity of soil microcosms in humid regions can be adequately evaluated only if soil samples are incubated at different soil moisture contents. A complete account of actinobacteria and proteobacteria requires the levels of soil moisture corresponding to the maximum capillary-sorption moisture and capillary moisture, respectively. The bacterial diversity, whose value was maximum on the 40th day of succession, was higher in soddy gley soil than in burozem. The taxonomic structures of the bacterial communities of these two types of soil were different. After wetting chernozem samples from arid regions, the soil bacterial community changed insignificantly with time and drastically differed from that of soils from humid regions. The difference in the bacterial diversity of soils was the most distinct when it was evaluated by measuring the proportion between proteobacteria and actino-bacteria. PMID- 11785143 TI - [Mycological characterisation of cultural layers of soil in medieval Russian settlements]. AB - Microbiological analysis showed that the cultural layers of soils in excavated medieval Russian settlements differ from the surrounding soils in that the cultural layers have more fungal spores, their morphology is more diverse, the species diversity of microscopic fungi is higher, and the Penicillium species that are able to grow at an elevated temperature (37 degrees C) are more frequent. PMID- 11785144 TI - [All-Russian Scientific Conference "Prospects of Development of Soil Biology" (on 100th birthday of Academician E N Mishustin)]. PMID- 11785145 TI - Reuben J. Silver. Award for Distinguished Contributions to Applied Psychology as a Professional Practice. PMID- 11785146 TI - Practicing professional psychology. AB - The practice of professional psychology generally has consisted of assessment and intervention. This article describes the functioning of one practitioner's activities. For assessment, the model described emphasizes point predictions and actuarial approaches whenever those are available. The discussion includes descriptions of specialization and expansion of practice areas, as well as the need for involvement in advocacy activities and professional associations. PMID- 11785147 TI - Juris G. Draguns. Award for Distinguished Contributions to the International Advancement of Psychology. PMID- 11785148 TI - Toward a truly international psychology: beyond English only. AB - It is contended that the development of a truly international psychology is obstructed at this point by the massive disregard of contributions that are published in languages other than English. The role of English as a mutually agreed-on principal medium of international communication in psychology is endorsed. At the same time, 11 suggestions are presented to overcome the linguistic isolation from the communities of psychologists in which languages other than English are used to disseminate findings and conceptions. PMID- 11785149 TI - Karen L. Hanscom. International Humanitarian Award. PMID- 11785150 TI - Treating survivors of war trauma and torture. AB - Psychologists are in a unique position to assist individuals and groups in the world who have survived torture and war trauma. Symptoms of posttraumatic stress disorder and other psychological diagnoses can be treated effectively by mental health professionals and trained lay counselors in the smallest of communities in the world. This article proposes a model for the treatment of survivors of torture and war trauma. This model has been designed to be useful to mental health professionals and to lay individuals in communities who constitute the front line in treatment: health providers, midwives, ministers, and teachers. The model is presented through examples of its use in the training of mental health counselors in the United States and in the training of promotores (health promoters) and comodrones (midwives) in Guatemala. PMID- 11785151 TI - Alan D. Baddeley. Award for Distinguished Scientific Contributions. PMID- 11785152 TI - Is working memory still working? AB - The current state of A. D. Baddeley and G. J. Hitch's (1974) multicomponent working memory model is reviewed. The phonological and visuospatial subsystems have been extensively investigated, leading both to challenges over interpretation of individual phenomena and to more detailed attempts to model the processes underlying the subsystems. Analysis of the controlling central executive has proved more challenging, leading to a proposed clarification in which the executive is assumed to be a limited capacity attentional system, aided by a newly postulated fourth system, the episodic buffer. Current interest focuses most strongly on the link between working memory and long-term memory and on the processes allowing the integration of information from the component subsystems. The model has proved valuable in accounting for data from a wide range of participant groups under a rich array of task conditions. Working memory does still appear to be working. PMID- 11785153 TI - Irving I. Gottesman. Award for Distinguished Scientific Contributions. PMID- 11785154 TI - Psychopathology through a life span-genetic prism. AB - The variation observed in individual differences for normal and psychopathological behaviors has genetic factors as a major contributor at the most distal end of a complex gene-to-behavior pathway. Research into the etiologies of such major mental diseases as schizophrenia is facilitated by adopting the approach used for complex adaptive systems as pursued by those who study coronary artery disease and diabetes. Putative risk factors for developing the liabilities to the major disorders can be inferred from population genetic strategies using twins, families, and adoptees. Weights to indicate the relative importance of such risk factors require a perspective from the use of effect sizes and odds ratios so as to make the most efficient use of scarce resources. The challenge to the field of psychology is to join in with cross-disciplinary ventures and to adapt to rapid changes with innovations in research strategies. PMID- 11785155 TI - Michael M. Merzenich. Award for Distinguished Scientific Contributions. PMID- 11785156 TI - David T. Lykken. Award for Distinguished Scientific Applications of Psychology. PMID- 11785157 TI - Parental licensure. AB - Most of the 1,400,000 men currently locked up in American prisons would have become tax-paying neighbors had they been switched in the hospital nursery and sent home with a mature, self-supporting, married couple. The parent with whom they did go home would in most instances not have been fit to adopt someone else's baby. It is argued that perhaps the only effective way to reduce crime and the other pathologies of the growing American underclass--apart from building still more prisons--would be to require from persons wishing to birth and rear a child of their own those same minimal criteria usually expected in adoptive parents. For evolutionary reasons, human beings are reluctant to interfere with the procreational rights of any person, no matter how immature, incompetent, or unsocialized he or she might be. In consequence, human beings tend not to think about the right of the child to a reasonable opportunity for life, liberty, and the pursuit of happiness. PMID- 11785158 TI - Marlene Behrmann. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785160 TI - Norman B. Schmidt. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785159 TI - Stephen A. Maren. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785161 TI - Duane T. Wegener. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785162 TI - Andrew J. Elliot. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785163 TI - James J. Gross. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785164 TI - Paul A. S. Breslin. Award for Distinguished Scientific Early Career Contributions to Psychology. PMID- 11785165 TI - Su Yeong Kim. Edwin B. Newman Graduate Research Award. PMID- 11785166 TI - Martha Bernal. Award for Distinguished Senior Career Contributions to the Public Interest. PMID- 11785167 TI - Edward Dunbar. Award for Distinguished Early Career Contributions to the Public Interest. PMID- 11785168 TI - Susan D. Cochran. Award for Distinguished Contributions to Research in Public Policy. PMID- 11785169 TI - Emerging issues in research on lesbians' and gay men's mental health: does sexual orientation really matter? AB - Theoretical writings and research suggest that the onset, course, treatment, and prevention of mental disorders among lesbians and gay men differ in important ways from those of other individuals. Recent improvements in studies of sexual orientation and mental health morbidity have enabled researchers to find some elevated risk for stress-sensitive disorders that is generally attributed to the harmful effects of antihomosexual bias. Lesbians and gay men who seek mental health services must find culturally competent care within systems that may not fully address their concerns. The affirmative therapies offer a model for intervention, but their efficacy and effectiveness need to be empirically documented. Although methodological obstacles are substantial, failure to consider research questions in this domain overlooks the welfare of individuals who may represent a sizable minority of those accessing mental health services annually. PMID- 11785170 TI - Ludy T. Benjamin, Jr. Award for Distinguished Career Contributions to Education and Training. PMID- 11785172 TI - Alan M. Lesgold. Award for Distinguished Contributions of Applications of Psychology to Education and Training. PMID- 11785171 TI - A brief history of the psychology course in American high schools. AB - Psychology has been a part of the high school curriculum for the past 170 years in a variety of forms, in classes labeled mental and moral philosophy mental hygiene, personal adjustment, child development, human relations, and psychology. This abbreviated and selective account traces that history, including the considerable role played by the American Psychological Association. This history focuses on the social and educational contexts that led to changes in the nature of high school psychology classes and concludes with comments about the value of precollege psychology classes. PMID- 11785173 TI - The nature and methods of learning by doing. AB - This presentation reviews some of the psychological research on learning by doing and discusses the role that learning-by-doing approaches can play in education and training. It includes a discussion of the author's implementations of this approach and the lessons learned from these implementations. Improved forms of learning by doing now can be supported by information technologies, and there are prospects for extensions to group learning by doing and group learning from examples in the near future. PMID- 11785174 TI - Marvin R. Goldfried. Award for Distinguished Professional Contributions to Knowledge. PMID- 11785175 TI - Integrating gay, lesbian, and bisexual issues into mainstream psychology. AB - Despite the growing clinical and research literature dealing with gay, lesbian, and bisexual (GLB) issues, mainstream psychology has tended to ignore much of the work that has been done in this area. This article illustrates how clinical and research writings on GLB issues continue to remain invisible to mainstream psychology in such areas as life span development and aging, teenage suicide, substance abuse, victimization and abuse, and family and couple relationships. It also deals with some of the determinants of well-being among GLB individuals, such as family support, and notes the benefits accruing to mainstream psychology from studying GLB issues. A network of family members within psychology having GLB relatives has been formed--AFFIRM: Psychologist Affirming Their Gay, Lesbian, and Bisexual Family--and is dedicated to supporting its own family members, encouraging other family members to do likewise, supporting research and clinical work on GLB issues, and closing the gap between GLB clinical and research work and mainstream psychology. PMID- 11785176 TI - JoAnne Pedro-Carroll. Award for Distinguished Professional Contributions to Public Service. PMID- 11785177 TI - The promotion of wellness in children and families challenges and opportunities. AB - This article considers the effects of marital disruption on children and families, using a risk and resilience perspective. The challenges that parental divorce poses for children are widely recognized; however, less attention has been given to strategies for promoting children's resilience and healthy developmental trajectories. The purpose of this article is to redress that imbalance by highlighting the importance of understanding pathways toward risk and resilience in children in the aftermath of divorce and the ways in which this research can be integrated into effective, evidence-based preventive interventions and proactive social policies that foster supportive parent-child relationships and psychological wellness in children and families. PMID- 11785178 TI - [Antibiotic resistance of Staphylococcus aureus strains isolated in two different Warsaw hospitals]. AB - S. aureus strains isolated in the same period from different specimens obtained from patients of two different hospitals were compared. The significant differences were observed in the frequency of resistance determinants between strains of these hospitals. The most important was the difference in the prevalence of MRSA. In the first hospital the percentage of MRSA was 40% whereas in the second one only 20%. The resistance to the other antibiotics was also compared, and independently from the compared group: MRSA, MSSA or all, the prevalence of resistance determinants was higher in the first hospital than in the second. Although the frequencies of MRSA in both investigated hospitals were relatively high comparing to the other European countries and in the first hospital even alarming, isolated MRSA strains are less resistant to other antibiotics than MRSA in other countries. PMID- 11785179 TI - [Biochemical typing as a method of differentiating group B streptococcus]. AB - In epidemiological studies on the group B streptococcus the serological typing is used. The paper present the results of a study on usefulness of biochemical typing for differentiation of the group B streptococcus. For that purpose, 210 strains descended from colonized infants and pregnant women were put to typing with both of mentioned methods. We showed that each of the method distinguishes similar number of biotypes and serotypes. However, ought to be marked that significant number of strains (93.8%) belonged to the three out of eight biochemical types. Similar results were achieved in serological typing, three of the most numerous serotypes contained 81.4% strains. Analysis of the relationship between serological and biochemical types did not reveal statistical association because the strains belonged to various serotypes. Obtained results show that both methods of typing--biochemical and serological, have similar value in differentiation of the strains. The method of biochemical typing is quite simple and can be used in laboratory conditions. PMID- 11785180 TI - [Utilization of exogenous siderophores by enterococci]. AB - The study was undertaken to investigate the ability of enterococci to assimilate iron via siderophores of bacteria living in the same habitats in the human organism. The potential recipients of exogenous siderophores were six Enterococcus faecalis and six Enterococcus faecium strains, isolated from clinical materials of human origin. The donors of siderophores were Gram-negative rods (various species of the Enterobacteriaceae, Pseudomonas and Acinetobacter) and Gram-positive cocci (various species of Staphylococcus and Streptococcus). All of the investigated E. faecium and only two E. faecalis strains demonstrated the ability to utilize the siderophores of the aforementioned bacterial groups, predominantly the chelators of Gram-negative rods, those of Gram-positive cocci were utilized to a smaller extent. Four recipient strains from E. faecalis species did not demonstrate the ability to utilize siderophores synthesized by all of 40 investigated donor strains. PMID- 11785181 TI - [Surface properties of Lactobacillus strains. I. Hemagglutination and hydrophobicity]. AB - Bacteria possess many surface membrane properties, both mechanical and biochemical, that allow them to interact with their environment These properties may affect a host in either positive (beneficial) or negative (pathological) ways. All surface properties of bacteria are yet unknown therefore we attempt to increase our knowledge regarding specific strains of lactobacilli, by examining the known properties including hemagglutination and hydrophobicity. The purpose of this study was to evaluate the cell surface properties of certain strains of Lactobacillus. These strains isolated from the human vagina and gastrointestinal tract were selected because of their antagonism toward aerobic and anaerobic bacterial pathogens. Part I discusses the hydrophobicity and hemagglutination abilities of these Lactobacillus strains. PMID- 11785182 TI - [Surface properties of Lactobacillus strains. II. Adherence to tissue culture surfaces]. AB - In the second part of this study, we evaluated the adherence properties of specific strains of Lactobacillus isolated from both the human vagina and gastrointestinal tracts. Lactobacilli taken from the vagina and GI tract were tested for their adherence to A431 vaginal tissue, and to CaCo-2 cells taken from the gastrointestinal tract. The Lactobacillus strains with the most marked adherence to the respective cell lines were examined under the electron microscope. These images revealed the presence of a substance morphologically resembling slime, which probably possess unknown active properties. PMID- 11785183 TI - [Adhesion of human granulocytes and T lymphocytes to vascular endothelial cells after stimulation with Bacteroides fragilis endotoxin and enterotoxin]. AB - The aim of presented study was to estimates the number of human granulocytes and T lymphocytes adhering to 1 mm2 of vascular endothelial cell culture stimulated by Bacteroides fragilis endotoxins (LPS) and enterotoxin (BFT). HMEC-1 cells were activated with bacterial preparations at the concentration of 10 (micrograms/ml for 4 and 24 hours. Granulocytes and T lymphocytes were isolated from peripheral blood of healthy blood donors. The adhesion tests of granulocytes and adhesion tests of resting and activated with PMA (at the concentration of 10 ng/ml) T lymphocytes to the non-stimulated and stimulated by B. fragilis compounds (LPS and BFT) vascular endothelium were performed. The number of viable leukocytes, which adhered to the endothelium, was determined using inverted microscope (magnification 200x). The results were presented as the number of viable cells adhering to 1 mm2 of the endothelial cell culture. The results of experiments indicate that granulocytes and T lymphocytes (resting and after activation with PMA even in greater number) adhere to the endothelial cells stimulated by B. fragilis endotoxins and enterotoxin. B. fragilis toxins are weaker stimulants of human leukocyte adhesion to the HMEC-1 cells than E. coli O55:B5 LPS. B. fragilis LPS and BFT preparations stimulate endothelial cells to the adhesion of granulocytes in similar manner, whereas the activation of vascular endothelium to the adhesion of T lymphocytes is differentiated. PMID- 11785184 TI - [Ability of acceptance for bacteriophages during verotoxin production by bacilli of the Enterobacteriaceae family]. AB - Lysogenised verotoxigenic strains are the source of structural genes of verocytotoxins (stx-1 and stx-2) for the others intestinal bacili. The aim of the study was to estimate the ability of transfer of bacteriophages induced with UV irradiation from reference verotoxigenic strains of E. coli O157:H7 (CB571 and EDL933) into 125 wild-strains of bacili of Enterobacteriaceae family. None of tested recipient strains showed the production of cytotoxin on Vero and HeLa cell lines, what was acknowledged as the lack of six genes. Contrary to the laboratory strain of E. coli C600 none of 125 tested recipient strains accepted the phages. Obtained lysogenised laboratory strains of E. coli C600/CB571 and E. coli C600/EDL933, besides of the ability to produce verotoxins (with the presence of stx-1 and stx-2 genes), did not differ phenotypically and genotypically from parent strain of E. coli C600. The estimation of the ability to transfer of phages carried stx-1 and/or stx-2 genes was impossible because of too small number of tested wild strain of bacili or because of really low frequency of acceptation of phages by wild strains of intestinal bacili. PMID- 11785185 TI - [Tests for studying invasive properties of selected Proteus mirabilis strains]. AB - Proteus mirabilis is an important pathogen of the urinary tract infections (UTI). Lipopolysaccharide (LPS, endotoxin) is one of the pathogenic factors of pathogenicity of these bacteria. In this paper we described the invasion of L929 mouse fibroblasts by P. mirabilis strains, classified into the O10, O23, O30, O43 serogroups. The maximal invasiveness was observed between 4-6 hours of incubation of the tested cells with bacteria. The cytotoxic effect slightly increased with the incubation time, probably as a result of the production of HpmA hemolysin. Incubation of L929 fibroblasts with LPS led to decrease of bacterial invasiveness. We observed that with the time of incubation of L929 cells with LPS (2-22 h), the invasiveness decreased (longer incubation time with LPS--weaker penetration). PMID- 11785186 TI - [Influence of newly synthesized sesquiterpenes--analogs of taxol on multiplication of herpes simplex virus (HSV-1MC) and retrovirus (Mo-MSV)]. AB - The study comprised newly synthesized sesquiterpenoid analogs of taxol. The synthesis of the compounds was performed at the Institute of Organic Chemistry, Polish Academy of Sciences. Cytotoxicity of the compound was assessed using formazan method. In in vitro studies the cell cultures were infected with HSV 1MC. The tested compounds were added in different concentrations to the cell culture after viral infection. Titer of the virus was expressed in TCID50/ml at particular stages of the experiments. In in vivo experiments NMRI mice were infected intramuscularly with a Moloney murine sarcoma virus (Mo-MSV). Tested compounds were administered to the mice intravenously on the day of virus inoculation. In Mo-MSV-infected mice dynamics of tumor progression and regression was assessed, as well as a mean time interval of tumor disappearance. Among the compounds tested: isovellerol-13-N-benzoyl-(2'R,3'S)-3'-phenylisoserinate, 5 deoxy-lactarolid B 8-[N-benzoyl-(2'R,3'S)-3'-phenylisoserinate] and isolactarorufin 8-epi-[N-benzoyl-(2'R,3'S)-3'-phenylisoserinate] showed significant antiviral activity in in vitro experiments. In in vivo experiments only lactarorufin A 8-[N-benzoyl-(2'R,3'S)-3'-phenylisoserinate] significantly inhibited the development of tumors and shortened the time of their total regression in the course of Mo-MSV infection. PMID- 11785187 TI - [Etiologic agents of fungemia in hospitalized patients]. AB - The aim of performed examinations was the analysis of fungi as etiological agents of blood infections in patients hospitalized in surgical wards, internal medicine wards and intensive care units of the Medical Academy Central Clinical Hospital in Warsaw. Blood samples from patients hospitalized in 1997 were examined. Peripheral blood samples were incubated in BacT/Alert system (Organon Teknika, USA). Positive blood samples were inoculated on Sabouraud medium with chloramphenicol (bioMerieux, France or Oxoid, England). The time of cultivation was from 48 hours to 7 days at 30 degrees C. Fungal strains were identified by standard mycological procedures with the use of chromogenic medium BBL CHROMagar Candida (Becton Dickinson, USA) and biochemical test ID 32 C (bioMerieux, France). Susceptibility of strains to antifungal agents was determined by ATB FUNGUS method (bioMerieux, France). The total number of positive blood cultures in 1997 was 1380. Forty-two fungal strains were isolated from blood samples (3%). Strains belonged to the following species: C. albicans (17 isolates), C. parapsilosis (15), C. glabrata (3), melibiosica (2), C. pelliculosa (2), C. guilliermondii (1), C. tropicalis (1) and T. beigelii (1). Among fungi cultured from patients hospitalized in operative wards dominated C. parapsilosis (11) and C. albicans (10) strains, whereas from patients hospitalized in conservative wards most often C. albicans (6) strains were isolated. Candida strains were mostly susceptible to antifungal agents tested. It was interesting to culture Trichosporon beigelii (T. cutaneum) strain as an etiological agent of fungemia. This strain was multidrug-resistant. PMID- 11785188 TI - Cultural sensitivity for aboriginal hemodialysis patients. AB - As the numbers of Aboriginal hemodialysis patients in Manitoba are dramatically escalating, we must explore ways of providing more culturally effective care. Knowledge and understanding of cultural differences are essential in that the potential for conflicting medical paradigms or explanatory models of illness may create obstacles to achieve this goal. We need to pay heed to Aboriginal communities that have developed effective programs, recognizing that Aboriginal input is critical to the success of any plan for Aboriginal people. In keeping with these understandings, Winnipeg's Health Sciences Centre has undertaken an initiative to improve the cultural sensitivity within the hemodialysis unit. The project is currently in the assessment phase and has undertaken a series of sharing circles or focus groups to solicit patient input. The following article will describe this cultural sensitivity initiative. It is hoped that this initiative will enhance a respectful and trusting relationship, allowing our Aboriginal patients to become partners in their care. PMID- 11785189 TI - Understanding hepatitis C. AB - Chronic hepatitis C virus (HCV) infection affects over 170 million people worldwide and is a common cause for liver transplantation in Canada. The prevalence of HCV infection in the dialysis population is estimated to be 20% to 50%. Today, intravenous drug use remains the most common route of transmission. The risk of acquiring HCV infection in patients on long-term hemodialysis is expected to decrease because of the screening of blood products for HCV. The diagnostic tests for hepatitis C include anti-HCV, HCV RNA, serum ALT levels, and liver biopsy. Liver biopsy is the definitive diagnostic procedure. Of patients acutely infected with the virus 50% to 85% will become carriers. HCV infection progresses slowly and the minority of patients develop cirrhosis over 20 years. The risk of hepatocellular carcinoma is increased once cirrhosis is present. The current standard of treatment that employs interferon and ribavirin has its limitations and is not indicated for many patients groups, such as patients on long-term hemodialysis. Interferon monotherapy is possible but is poorly tolerated by patients on dialysis. Patient and family education, as well as counselling, are important in that patients infected with HCV should be partners with health care providers in the management of their disease. PMID- 11785190 TI - The prevalence and incidence of hepatitis C virus infections among dialysis patients in The Netherlands: a nationwide prospective study. PMID- 11785191 TI - Effect of hepatitis C infection and renal transplantation on survival in end stage renal disease. PMID- 11785192 TI - Ensuring temperature balance during hemodialysis: the optimal dialysis solution temperature. PMID- 11785193 TI - Competency-based education. PMID- 11785194 TI - Nephrology and the Internet--personal digital assistants. PMID- 11785195 TI - [Physiological significance of the gastric somatostatin]. PMID- 11785196 TI - [Comparative analysis of qualitative assessment of sections of the small intestine mucosa in stereoscopic microscope with histological evaluation of biopsy specimen]. PMID- 11785197 TI - [Pancreolauryl test, glucose tolerance test and endoscopic retrograde cholangiopancreatography in the diagnosis and monitoring of chronic pancreatitis]. AB - Fifteen patients with chronic pancreatitis were qualified for surgical treatment on the basis of the results of endoscopic retrograde cholangiopancreatography, pancreolauryl test and glucose tolerance test. Significant changes according to Cambridge scale correlated with exocrine-endocrine pancreatic failure. In patients with Wirsung duct of diameter above 6 mm Puestow operation was performed while in patients with narrow Wirsung duct resection procedures were carried out. Control examinations carried out one year after Puestow operation demonstrated in all 10 patients lack of improvement both in the exocrine and endocrine pancreatic function. In 70% of the patients after anastomotic operation and in 80% of the patients after resections, complete regression of preoperative pain was observed. PMID- 11785198 TI - [Serum concentration of prolactin, gastrin and glycocholic acid in patient with peptic ulcer treated with ranitidine]. AB - In 66 patients with peptic ulcer (11 with gastric ulcer, 55 with duodenal ulcer, 19 women, 47 men) the serum concentrations of prolactin, dehydrocholic acid and gastrin were determined. The studies were repeated after treatment with ranitidine: in 50 patients after three weeks and in 40 patients after another 30 days. During the first period ranitidine 2 x 150 mg was administered, while during the second period the dose was 1 x 150 mg. The results were compared with those obtained from 120 healthy subjects. Before starting the treatment prolactin levels were significantly higher than those in the control group. During the treatment a significant decrease of the levels was observed. Similar changes of prolactin concentrations were found in the group of 39 men with duodenal ulcer isolated from the studied patients, who were compared with a group of 50 healthy men. It was not found that the development of peptic ulcer and the treatment with ranitidine exerted and effect on the changes of gastrin and dehydrocholic acid concentrations. PMID- 11785199 TI - [Effectiveness and tolerance of selected Polish antacids in the therapy of duodenal ulcer disease. A placebo- and ranitidine-controlled study]. AB - In a randomized, open clinical trial we compared the efficiency of selected Polish antacids Alugastrin, Gastrin and Wikalina with ranitidine and placebo in the healing of duodenal ulcer, pain relief and drug toleration. One hundred and ten outpatients completed the study. The trial showed that antacids and ranitidine had similar rates of duodenal ulcer healing which were significantly better than placebo. After 4 weeks of treatment with Alugastrin, Gastrin, Wikalina and ranitidine the healing rates were 70%, 76%, 71% and 81%, respectively, compared to placebo 44%. Efficiency of antacids in pain relief was similar to placebo and slightly lower than ranitidine. Antacids were well tolerated, except for hypermagnezemia and urine alkalization caused by Gastrin and Wikalina. We conclude that studied antacids are as effective as ranitidine in promoting healing of duodenal ulcer, but because of side effects they are not recommended for maintenance therapy. PMID- 11785200 TI - [Analysis of anionic gap and lactic acid levels significance in metabolic acidosis in small children]. PMID- 11785201 TI - [Duodenogastric reflux in patients with irritable bowel syndrome]. PMID- 11785202 TI - [14-years old boy with chronic gastritis]. PMID- 11785203 TI - [Haematologic changes in gastritic cancer]. AB - Haematologic disturbances in 13 cases of gastric cancer are described. All the patients had anemia of different origin. Increased leukocytosis was observed in half of the cases, leukaemia reaction in one third. Haemolysis was present in 50% of cases. Thrombocytopenia coexisted most frequently with disseminated intravascular coagulation in 4 patients. Bone metastases were visualised as osteolytic foci with radiological methods or increased capture of isotopic marker in the bones under scintigraphic examination. Under the microscope neoplastic metastases were found in bone marrow smears of 5 patients. All patients displayed symptoms of gastric ulcer disease acute or chronic phase. In some cases only repeated gastroscopic examination and mucosa biopsy was the only way to confirm cancer. In other cases the diagnosis was made after the histopathologic examination of the resected stomach, in still others by a section. PMID- 11785204 TI - [Biochemical and clinical aspects of the poisoning with ethylene glycol]. PMID- 11785205 TI - Rolling out the red carpet for employees. Investing in health care's greatest asset. AB - Employees are hospitals' greatest asset, yet they're often treated as an "expense." Some lessons from corporate America show why investing in employee retention and training--even in economically rough times--pays off in the long term. PMID- 11785206 TI - Building healthier communities in challenging times. PMID- 11785207 TI - Ending the culture of blame. A look at why medical errors happen--and what needs to change. AB - A group of high-profile hospital leaders is working to find solutions to medical errors that target systemic problems rather than individuals. Their actions are highlighted here. PMID- 11785208 TI - Open wide. Dental care puts smiles on the faces of North Carolina kids. AB - When kids' dental needs get overlooked, their whole health suffers. That's why FirstHealth of the Carolinas listened thoughtfully to school health nurses who told them about the impact that tooth decay and abscesses were having on kids without insurance or whose families relied on Medicaid. PMID- 11785209 TI - Intermediate sanctions: tax traps for the unsuspecting. AB - In an effort to keep your CEO from leaving, your board is overly generous--with salary, benefits, and perks. But if that generosity goes far beyond the norm for your region and type of organization, you could be letting your CEO and fellow trustees in for some very stiff penalties. PMID- 11785210 TI - Putting all the pieces together. The complete board needs the right mix of competencies. AB - Now that most system and hospital boards are smaller, few can afford to include members who don't contribute to the organization's strategic plan. So boards are applying new criteria for choosing members--criteria based on candidates' personal characteristics, skills, knowledge, and perspective. PMID- 11785212 TI - Health care.com. Trustees may soon find themselves on the board of an Internet startup. AB - The Internet is no longer a technology gimmick or a luxury for providers. It is already changing marketing strategies and may some day fundamentally alter the way health care is delivered. PMID- 11785211 TI - The age wave. AB - The first group of Baby Boomers will start receiving Medicare in about 10 years. These patients will be savvier and more demanding than any group before them. Moreover, the changing demographics mean a major shift from acute to chronic care. PMID- 11785213 TI - What price coverage reform? AB - Coverage reform in the next few decades is all about making choices, paying close attention to what people really need and want, and giving it to them in smarter, more efficient ways than providers have done in the past. PMID- 11785214 TI - Point/counterpoint. Board compensation: the time is now. PMID- 11785216 TI - Trustee workbook 1. Stewardship of the future. PMID- 11785215 TI - Point/counterpoint. Let's not take the trust out of 'trustee'. PMID- 11785217 TI - Two rivers run through it. PMID- 11785218 TI - Genomics. Medicine's future in our molecules. AB - Decoding the messages contained within our DNA and applying them to clinical therapies will revolutionize medicine and health care delivery. But what does it all mean and what are the implications for providers? PMID- 11785219 TI - Creating healthy futures. 2000 NOVA Award winners. AB - Winners of this year's NOVA awards, sponsored by the American Hospital Association and H&HN magazine, all share a broad definition of health. These five stars of community benefit also understand that a community and a health care organization share responsibility for what creates health, and that collaborative efforts are the only way to sustain innovative programs. PMID- 11785220 TI - Effective boards: working smarter to meet the challenge. AB - The responsibilities that boards must shoulder these days weigh a lot more heavily than they used to. But what are trustees doing about them? Here's some advice on what you should be doing and how you can do it. PMID- 11785221 TI - Patient safety: it starts at the top. PMID- 11785222 TI - Secrets of a successful board retreat. PMID- 11785223 TI - Be all that you can be. Information technology and quality care go hand in hand. AB - You might think you can't afford to invest a lot in information systems; but the fact is, you can't afford not to. Once you see how various systems are used to improve quality of care and reduce medical errors, you'll realize that an investment today will pay you dividends for years to come. PMID- 11785224 TI - Rebuilding patient trust. Jump in. AB - Many people think of hospitals more as businesses than as care providers, and they are wary. As the best connection to their communities, trustees can go a long way to restoring the trust that's gotten lost among the mergers, employee layoffs, and insurance problems. But first, they have to seek community feedback and trust what they hear. PMID- 11785225 TI - The Circle of Life. The AHA recognizes end-of-life programs with awards. AB - The Circle of Life awards were presented for the first time this year by the American Hospital Association to highlight breakthrough innovations in end-of life care. The three award winners, profiled here, demonstrate that care, comfort, and compassion must go hand-in-hand in the final stage of life. PMID- 11785226 TI - Investing your money: the long and the short of it. AB - Because of rapid changes in the stock market and the health care environment, boards must rethink their short- and long-term investment strategies. Experts offer practical advice about how to restructure your investments for the new economy. PMID- 11785227 TI - Outpatient PPS: how the AHA is working for you. PMID- 11785228 TI - Owning a physician practice. Anatomy of a turnaround. AB - While many organizations are divesting their physician practices, Integris Health System decided to stick with theirs. Here's how they cut their losses by more than half in one year and plan to break even by next year. PMID- 11785229 TI - Health care systems: the emperor has no clothes. AB - Hospitals that merged and joined systems in the last 10 years need to revisit their decisions and determine whether their good intentions have actually paid off. PMID- 11785230 TI - Trustee workbook 3. E-health and the board: the brave new world of governance, Part 1. PMID- 11785231 TI - Pay for performance: what trustees should be applauding. AB - The responsibilities of the board's compensation committee go beyond just determining annual pay. The committee must develop a plan that outlines organizational goals and identifies the CEO's accountabilities. Then trustees can fulfill their fiduciary and stewardship roles by providing continuous feedback to their CEO. PMID- 11785232 TI - The right fit. Recruiting for your board. AB - If you need special skills, connections, and personalities for your board, you can't leave trustee recruitment to chance or the last minute. Following the Children's National Medical Center's eight-step recruitment process may help you make just the right fit. PMID- 11785234 TI - A modern marriage. Maintaining independence through a 'virtual' partnership. AB - Take two community hospitals that want to maintain their independence but also want to enjoy some of the benefits that a merger can afford, and what do you get? In West Virginia, the answer is a "virtual" merger--and it's working for them. PMID- 11785233 TI - Breaking away. Is the divorce rate for hospital mergers and systems climbing? AB - The jury is still out on whether a recent spate of hospital de-mergers and system break-ups represents a trend or a natural readjustment. But one thing is for sure -advice from trustees who have been through a hospital divorce can save you from repeating their emotionally wrenching experiences. PMID- 11785235 TI - Confronting HIPAA. AB - Just when you thought it was safe to come out after Y2K, along comes the Health Insurance Portability & Accountability Act, which--if you're not there yet--will force you head first into the electronic age. HIPAA comes with a big price tag, but it may save you money in the long run by standardizing data. BOTTOM LINE: Compliance is not an option. PMID- 11785236 TI - Overcoming the myths of health care. PMID- 11785237 TI - Strategic planning. Is strategic planning relevant anymore? PMID- 11785238 TI - An elementary question. Why would a health care system run a school? AB - INTEGRIS Health System in Oklahoma may be in a class by itself when it comes to improving community health. Its latest effort--a collaboration with the Oklahoma City school system to co-manage a struggling elementary school--has begun a dramatic turnaround for the school and for the health and well-being of its students. PMID- 11785239 TI - Patient safety, thy name is quality. AB - Trustees must take the lead in communicating the importance of an organization wide quality program. Patient safety is a natural outgrowth of an aggressive and nonpunitive approach to quality. PMID- 11785240 TI - Meeting in the middle. Lessons from an interfaith merger. AB - Success stories of mergers between Catholic and non-Catholic hospitals are few and far between. Such mergers involve all of the usual complications in addition to potential conflicts of mission and control. But with the proper planning and flexibility, it's possible for such a merger to work. This case study shows you how it's done. PMID- 11785241 TI - Selecting the right physicians for your board. PMID- 11785242 TI - Culture clash ... and how to deal with it. AB - Corporate culture, or an "organization's personality," is one of those intangible attributes frequently overlooked when institutions are considering a merger. But it can make all the difference to success or failure. It's crucial that leaders understand the significance of corporate culture, how to read it, and how to work with it. PMID- 11785243 TI - The quality of mercy is not strained. Sister Roch: the AHA's new chair-elect. Interview by Mary Grayson. AB - Sister Mary Roch Rockledge, chairwoman of the board of the Sisters of Mercy Health System-St. Louis, is the AHA's chair-elect. Sister Roch's strong sense of mission guides her vision for the health care system's future. PMID- 11785244 TI - Ten financial components of a successful hospital/system. AB - The author describes the main causes of many hospitals' and systems' bleak financial status and recommends 10 actions to help solve the problems. PMID- 11785245 TI - The invisible gap: organizational liability and the role of governance. PMID- 11785246 TI - Trustee workbook 4. Information, E-health, and the board: the brave new world of governance, Part 2. PMID- 11785247 TI - Ask trustees who know. Interview by Laurie Larson. AB - Five of your trustee peers share their expertise on board education, fundraising, community representation, what it means to be a board chair, and what physicians can bring to your board. PMID- 11785248 TI - [Ontogenesis and population: evaluation of developmental stability in natural populations]. AB - Ontogenetic and population studies traditionally develop independently. At the same time, the relevance of specific analysis of a specimen as ontogenesis for both correct assessment of populations and their dynamics in time and space and understanding the mechanisms underlying population processes is becoming more and more clear. Developmental stability serves as the most general description of the developing organism status. The level of developmental noise commonly evaluated by fluctuating asymmetry is the main index of developmental stability. High developmental stability is maintained on the basis of genetic coadaptation under optimal developmental conditions. Coordinated changes in developmental stability and other homeostatic indices, including genetic, physiological, biochemical, and immune indices suggest that we consider the general status of the organism by evaluating its developmental stability. Evaluation of developmental stability as a measure of environmental stress, apparently, is the most promising. In practical terms, this allows us to evaluate and monitor environmental health under both natural and various anthropogenic conditions. Outlooks of this approach as relates to studies of developmental stability are discussed. PMID- 11785249 TI - [Possible application of the indices of developmental stability and photosynthetic activity for studying the states of natural plant populations using the weeping birch as an example]. AB - We have generalized the materials of population-phenogenetic studies of the weeping birch in different environmental conditions using developmental stability analysis and photosynthetic activity measurements. PMID- 11785250 TI - [Cytogenetic and anatomic features of the weeping birch in the 30-km zone surrounding the Novovoronezh nuclear power plant]. AB - We studied the development of the vegetative and generative spheres in the weeping birch from the 30-km zone surrounding the Novovoronezh nuclear power plant. Being the most sensitive ontogenetic stages, the mitotic and meiotic processes are capable of responding to the effects of various factors, including unfavorable environmental factors. Studies were carried out from 1998 to 2000 in Novovoronezh under conditions of potential hazard for normal development (a possible joint effect of chronic ionizing irradiation at low doses from the Novovoronezh nuclear power plant and elevated concentrations of some chemical substances as side products of the plant activity) and in the ecologically pure territory of the Biological Station Venevitinovo of the Voronezh State University. Significant deviations from the normal course of mitotic and meiotic processes have been recorded in the experimental variant and specific types of disturbances have been described. A suggestion has been put forward concerning some mechanisms underlying the weeping birch adaptation to unfavorable environmental conditions. Specifically, it was shown that the trees studied were of a mixoploid nature. No such studies have ever been carried out in the region of this nuclear power plant, one of the oldest in Russia. PMID- 11785251 TI - [Evaluation of developmental stability and cytogenetic homeostasis in populations of European green frogs (Rana esculenta-complex) under natural and anthropogenic conditions]. AB - The status of amphibians in populations subjected to anthropogenic influence of various natures has been evaluated. We studied the effect of complex anthropogenic influences as well as chemical and radiation pollution. The status of the specimens in populations was evaluated by morphological (developmental stability as the level of fluctuating asymmetry) and cytogenetic (micronucleus test) methods. Disturbed developmental stability and cytogenetic homeostasis have been observed in populations affected by anthropogenic factors, which indicates the changed status of the organism. PMID- 11785252 TI - [Ontogenetic approach to studying natural avian populations]. AB - The asymmetry of digit folidosis and the correlation of exterior characteristics have been studied in 20 passerine species. The level of the characteristic asymmetry depends on the phylopatry level and regularly increases in the species disposed to annual change of the nesting site. We assume that the revealed variability reflects interpopulation flow of genes. Age-, sex-, and biotope related changes associated with urbanization have been revealed in the correlation of characteristics. Older birds have more pronounced correlation of characteristics; it is also more specific for males than females. Correlation of characteristics is less pronounced in the urban avian populations. These differences are interpreted in terms of stabilizing selection within intraspecific groups. PMID- 11785253 TI - [Estimate of cytogenetic homeostasis in natural populations of some small murid rodents]. AB - Cytogenetic homeostasis in natural populations under natural conditions and anthropogenic stress was estimated according to the frequency of chromosome aberrations in somatic cells for six species of small mammals. Cytogenetic homeostasis was disturbed under the stress effect of increased density during population cycles, at the ecological periphery, and in the case of environmental chemical and radiation contamination. Cytogenetic homeostasis disturbances were related to changes in other indices of homeostasis, such as developmental stability and immune status, suggesting the use of the cytogenetic approach for estimating the general state of individuals in natural populations. PMID- 11785254 TI - [Morphological polyvariance of ontogeny in natural plant populations]. AB - The main patterns of expression of the morphological polyvariance of plants are discussed: diversity of biomorphs, pathways of ontogeny, and disturbances of morphogenesis. The diversity of biomorphs of tap root plants in different ecological conditions has been analyzed in detail. Promising directions of future studies have been formulated. PMID- 11785255 TI - [Genes controlling inflorescence structure and their possible role in evolution]. AB - Structural features of the shoot system and inflorescence are the most important morphological features, on which plant systematics are based. The present review provides information on the genetic control of shoot morphogenesis in the model plant Arabidopsis thaliana. The results obtained made it possible to reveal a small group of genes responsible for the main taxonomic features of the shoot structure in this species. Cloning of these genes opened new avenues for directed search of homologous genes in other plants. Comparative analysis of the shoot structure and studies of the function and expression of these genes in various plants suggest that morphological evolution may be based on changes in the pattern of expression of single regulatory genes. PMID- 11785256 TI - [Morphological diversification of fish as a consequence of the divergence of ontogenetic trajectories]. AB - The possibilities of the investigation of ontogenetic changes in the morphological features of fish using multidimensional "ontogenetic channels," within which individual ontogenetic trajectories run, are demonstrated using African barbs. (Barbus intermedius complex) as an example. The position of ontogenetic channels allows one to judge how the differences of adult individuals in morphological characters arise during development and how their morphological diversity is formed. PMID- 11785257 TI - [Retrospective estimate of the individual history of life in population studies on mammals]. AB - Analysis of the recording structures in mammals, such as dentine, cementum, or bone tissue, makes it possible to estimate the parameters of individual history of life: age at the moment of death, seasons of death and birth, growth rate, age of sexual maturation, etc. Using the reindeer (Rangifer tarandus) as an example, it has been shown what specific life features essential for population studies may be estimated when only mandibles with teeth are available. PMID- 11785258 TI - Cellular and lipopolysaccharide fatty acid composition of the type strains of Klebsiella pneumoniae, Klebsiella oxytoca, and Klebsiella nonpathogenic species. AB - The cellular and lipopolysaccharide (LPS) fatty acid compositions of the type strains of Klebsiella pneumoniae, K. oxytoca, K. terrigena, K. planticola, and "K. trevisanii" were studied. The cellular fatty acids of klebsiellae were presented by straight-chain saturated and monounsaturated, cyclopropane, and hydroxy fatty acids. Hexadecanoic, methylenehexadecanoic, octadecenoic and hexadecenoic acids prevailed. The K. pneumoniae strain mainly differed from the strains of other species by two and more times lower level of dodecanoic acid in cells. Variations of cyclopropane and unsaturated fatty acid contents in cells were observed. LPS fatty acids profiles of klebsiellae mainly consisted of straight-chain saturated and hydroxy fatty acids with predominance of tetradecanoic and 3-hydroxytetradecanoic acids. LPS fatty acids profiles of K. oxytoca, K. terrigena, K. planticola, and "K. trevisanii" strains were very similar and differed from that of the K. pneumoniae strain by higher levels of dodecanoic acid (approximately 5-6 times) and absence of 2-hydroxytetradecanoic acid. The obtained data indicated more close relatedness of K. oxytoca, K. terrigena, and K. planticola and some their remoteness from K. pneumoniae. PMID- 11785259 TI - [Reorganization of the strain's cellular lipids--degradation of anionic surfactants during "detergent" stress]. AB - Changes in the fatty acid composition and ultrastructure of Pseudomonas aeruginosa 1C strain--a destructor of alkyl sulphates under the effect of the stress evoked by sodium dodecyl-sulphate have been studied. It has been established that the "detergent" stress changes the ratio of the cell fatty acids (FA) towards the increase of their nonsaturation. Ultrastructural changes in the cells are revealed earlier than biochemical ones. Several stages in stress development have been distinguished. The escape from the stress state is performed both at the population level and at the level of individual cells, highly-resistant to dodecyl sulphate. PMID- 11785260 TI - [Peculiarities of linear growth of the melanin-containing fungi Cladosporium sphaerospermum Penz. and Alternaria alternata (Fr.) Keissler]. AB - Results on determination of radial (linear) growth rate of melanin-containing fungi Cladosporium sphaerospermum Penz. and Alternaria alternata (Fr.) Keissler concerning place of their isolation and ecologic peculiarities are presented in the paper. Essential differences, as to all studied indices of the strains of C. sphaerospermum strains, isolated from premices of the ChNPP 4th unit from the control strains of this species have been established. Only strain 34 of C. sphaerospermum, isolated from the cable driving region of the "Shelter" object, which did not differ from the control strains as to all the studied indices, made the exception. The radial growth rate was 2-4 times as low and variability amplitude 10-30 times as high in strains 60 and 5-1 of C. sphaerospermum, (which suffered high radiation load), as in the control strains of this species. The radial growth rate of C. sphaerospermum studied strains was an order lower as a whole than that of A. alternata strains. All the above said evidence for implementation of K-type vital strategy by C. sphaerospermum species and in this connection one can suppose its active growth on the surface of walls and ferroconcrete structures of the ChNPP 4th unit. Absence of differences, as to the studied radial growth indices, between A. alternata strains isolated from the ChNPP 4th unit premices and control strains of the species can evidence for the existence of A. alternata species under the conditions of high radioactivity in the surviving state. PMID- 11785261 TI - [Effect of heavy metals on the growth of soil streptomyces]. AB - The effect of heavy metals on the streptomycete pure cultures under solid and liquid nutrient media has been studied. There were revealed streptomycete forms sensitive and resistant to heavy metals. Streptomyces versipellis strain 1, S. griseoalbus strain 6, and S. viridogenes strain 570 belong to the first group. The increase of metal content in the agarized medium caused the decrease of the number and dimension of colonies, capacity for sporulation and loss of aerial mycelium, soluble pigment, and, at last, death. These cultures may be used as indicators of the soil heavy metal pollution in the future. The resistant streptomycete forms had good growth under experimental conditions and could accumulate the metals in the liquid media: S. flavovirens, strain 12,--about 230 micrograms of copper ions, S. albaduncus, strain 279,--209 micrograms of cadmium ions and S. alboviridis, strain 141-653 micrograms of lead ions per 1 g of dry mycelium. It is supposed that these streptomycetes, when assimilating the above metals in amounts required for life about can exclude them from the circulation and can decrease the metal negative influence on plants. PMID- 11785262 TI - [Species composition of Fusarium Link et Fr. fungal genera affecting agricultural plants and weeds in Uzbekistan]. AB - Phytopathogenic fungi of the Fusarium genus are represented on the agricultural plants and weeds by 17 species and 10 subspecies from the sections Roseum, Discolor, Sporotrichiella, Elegans, Martiella, Arachniotes in Uzbekistan. As to their occurrence frequency F. javanicum, F. lateritium, F. solani, F. oxysporum, F. heterosporum, F. moniliforme, F. gibbosum species are dominating ones. F. merismoides, F. redolens, F. nivale species occurred often F. sporotichiella, F. semitectum, F. culmorum, F. bucharicum, F. graminearum, F. avenaceum species occurred rarely. It was shown that the Fusarium species were more numerous in the central and southern regions of Uzbekistan than in the northern region. PMID- 11785263 TI - [Epiphytic phase of Erwinia amylovora and Pseudomonas syringae pv. syringae on orchard weeds]. AB - Epiphyte phase of phytopathogenic bacteria Erwinia amylovora and Pseudomonas syringae pv. syringae on the fruit garden weeds has been studied. It has been shown that healthy weeds of the fruit-tree stands can be an ecologic niche for Erwinia amylovora and Pseudomonas syringae pv. syringae which gives them an opportunity to survive as epiphytes. Strains of Pseudomonas syringae pv. syringae were isolated from seven studied weeds (47-49%) during the whole vegetation period (March-October). Strains of Erwinia amylovora distributed on the leaves of Arctium lappa L., Amarantus reflexus L. and Tripleurospermum inodorum (L) Sch. Vir. in the period of the disease intensive development on the pear-tree (June August). Cells of Erwinia amylovora were isolated from 12-14% of selected weeds. PMID- 11785264 TI - [An indirect hemagglutinin test for Rickettsia prowazekii cultivated by the Weigl method]. AB - The technology of preparing of a new ready for use diagnosticum for IHAT on the basis of polysaccharide of Rickettsia prowazekii cultivated by the Weight method has been developed. Technological conditions have been worked out, experimental series of the diagnosticum have been made and tested, high stability during the storage was confirmed which allows it to be recommended for the epidemic typhus laboratory diagnostics. PMID- 11785265 TI - [Use of associative cultures of cyanobacteria for tertiary treatment of sewage from yeast and alcohol plants]. AB - The associative cultures of cyanobacteria were selected which may be used for development of technology of tertiary treatment of sewage for yeast and alcohol production plants. Growth parameters of associations were studied during periodic and continuous cultivation. When studying the influence of flowing speed for some exponents of treatment it was shown that cultivation of cyanobacteria should be carried out with the change of volume not more than 0.01 h. Final treatment 0.010 h-1 in order to return sewage to natural water reservoirs may be carried out by means of Oscillatoria sp. in bioponds. PMID- 11785266 TI - [Strains of Pseudomonas fluorescens 3 and Arthrobacter sp. 2--degradation of polycyclic aromatic hydrocarbons]. AB - Pseudomonas fluorescences 3 and Arthrobacter sp. 2 strains were isolated from the association of microorganisms--destructors of oil hydrocarbons and were selected for their ability to grow on media with phenanthrene as the only source of carbon and energy. The P. fluorescens 3 strain is able to grow on naphthalene, fluorene, phenanthrene, and anthracene. Arthrobacter sp. 2 strain did not grow on naphthalene, but was able to destruct phenanthrene and fluorene. The destruction activity of these strains both in pure and mixed culture towards the latter compounds has been studied. The both strains destructed phenanthrene added into the medium in the amount of 0.2 g/l, and phenanthrene destruction by Pseudomonas fluorescences 3 achieved 98.5% in 6 days and that by Arthrobacter sp. 93.5% in 23 days. Bacterial growth has been evaluated while measuring protein concentration in samples. Bacteria were inoculated in quantities equivalent to 0.0015-0.0020 mg protein/l. The cell protein concentration achieved 35-40 mg/l for Pseudomonas fluorescences 3, and 85-92 mg/l for Arthrobacter sp. by the end of incubation. PMID- 11785267 TI - [Assessment of biological corrosion of ferroconcrete of ground-based industrial structures]. AB - One of the objects of a nuclear plant built in 1983 and put in 15-years long dead storage with the purpose to estimate the degree of contamination by rust hazardous microorganisms of ferroconcrete structures and to predict their biocorrosion state after putting in operation was a subject of microbiological investigation. The everywhere distribution of sulphur cycle bacteria (thionic and sulphate-reducing bacteria) on the surface and in the bulk of concrete structures, their confineness to corrosion products of concrete and bars of the investigated building have been shown. It has been demonstrated that sulphate reducing bacteria were the most distributed group in all the sampling points. An indirect estimation of participation degree of the microbial communities in the processes of ferroconcrete biological damages has been carried out as based on the accumulation intensity of aggressive gaseous metabolites--carbon dioxide and hydrogen. Probability of deterioration of biocorrosion situation under the full scale operation of the object has been substantiated. PMID- 11785268 TI - Use 'credit system' to give your DM programs a boost. PMID- 11785269 TI - Experts call for non-pharmacological intervention of high-normal blood pressure. AB - Why? Because new research suggests that even high-normal BP is associated with adverse events, and statistics show that a remarkably low percentage of people with high BP are receiving adequate treatment--or even any treatment at all. Get expert advice on what steps should be taken when patients have high-normal BP, and see how your organization is faring on a list of 13 quality indicators. PMID- 11785270 TI - DM pilot aims to further integrate mental health services into primary care. AB - Well-aware that patients will be much more likely to take advantage of mental health services in a primary care setting, a new model is being tested in Hawaii that seeks to further integrate mental health and traditional care by having physicians work alongside behavioral health specialists in their offices and exam rooms. The model borrows heavily from an earlier study that produced dramatic outcomes in chronically ill individuals who received targeted behavioral health interventions. Revisit the earlier study and see how researchers are now hoping to further push the envelope with a fresh approach. PMID- 11785271 TI - Interactive games boost outcomes in chronically ill children. AB - The challenges of managing a chronic disease are particularly tough on youngsters. However, one innovative new tool has shown that it can help the medicine go down a little easier in young patients. Studies show that a series of interactive games designed to educate and motivate children with chronic disease can not only help kids learn to cope with their disease in an entertaining way, it also can make a measurable impact on utilization. PMID- 11785272 TI - The fifth principle. Family physicians as advocates. PMID- 11785273 TI - Building dialogue. Aboriginal health and family physicians. PMID- 11785274 TI - Diagnosing ectopic pregnancy. PMID- 11785275 TI - Acute stroke management. PMID- 11785276 TI - Finasteride. Does it affect spermatogenesis and pregnancy? AB - QUESTION: A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets? ANSWER: To date, there are no reports of adverse pregnancy outcomes among women exposed to finasteride. Taking 1 mg of finasteride daily did not have any clinically significant effect on men's semen. Absorption through the skin while handling tablets is extremely unlikely to cause fetal exposure or harm. There is no reason to discontinue the drug. Motherisk is currently following up women who are pregnant or planning pregnancy and whose partners are taking finasteride. PMID- 11785277 TI - Dermacase. Herpes simplex virus. PMID- 11785278 TI - Do acetylsalicylic acid and other antiplatelet drugs prevent preeclampsia? PMID- 11785279 TI - Integrated model for mental health care. Are health care providers satisfied with it? AB - OBJECTIVE: To determine whether health care providers are satisfied with an integrated program of mental health care. DESIGN: Surveys using a mailed questionnaire. Surveys were developed for each of the three disciplines; each survey had 30 questions. SETTING: Thirty-six primary care practices in Hamilton, Ont, participating in the Hamilton-Wentworth Health Service Organization's Mental Health Program. PARTICIPANTS: Family physicians, psychiatrists, and mental health counselors providing mental health care in primary care settings. MAIN OUTCOME MEASURE: Satisfaction as shown on 5-point Likert scales. RESULTS: High levels of satisfaction with the model were recorded. Family physicians increased their skills, felt more comfortable with handling mental health problems, and were satisfied with the benefit to their patients. Psychiatrists and counselors were gratified that they were accepted by other members of the primary care team. Areas for improvement included finding space in primary care settings and better scheduling to allow for optimal communication. CONCLUSION: Family physicians, counselors, and psychiatrists expressed great satisfaction with a shared mental health care program based in primary care. PMID- 11785280 TI - [Direct supervision. Perceptions of ex-residents in family medicine]. AB - OBJECTIVE: To explore former residents' perceptions of their experience of direct supervision. DESIGN: Qualitative study using in-depth semistructured interviews. SETTING: Family practice unit (FPU) at Hopital Laval in Quebec city, Que. PARTICIPANTS: Twelve physicians who had been practising for 2 to 5 years and who did their family medicine residency in the FPU at Hopital Laval. METHOD: Twelve interviews lasting 1 to 2 hours conducted by someone with no connection to the teaching centre. Interviews were taped and transcribed in full. Results were analyzed using L'Ecuyer's developmental method. MAIN FINDINGS: The former residents thought direct supervision had helped them in relationships with patients and in getting to know themselves, and was still doing them good several years later. It was also a difficult and disturbing experience; it created performance anxiety, forcing residents into self-examination and allowing others to see them as they really are. Three things made the direct supervision process easier: a preparatory activity, a focus on learning rather than evaluation, and their supervisors' ability to adapt to their learning styles. CONCLUSION: The former residents appreciated direct supervision; in spite of the difficulties, it was worthwhile. This conclusion will encourage teachers to continue to be involved in direct supervision. PMID- 11785281 TI - Work in progress. Integrating physicians' services in the home. AB - OBJECTIVE: While increasing acuity levels and the concomitant complexity of service demand that physicians be involved in in-home care, conflicting evidence and opinions do not show how this can best be achieved. DESIGN: A phenomenologic research design was used to obtain insights into the challenges and opportunities of integrating physicians' services into the usual in-home services in London, Ont. SETTING: Home care in London, Ont. PARTICIPANTS: Twelve participants included three patients, two family caregivers, two family physicians, the program's nurse practitioner, two case managers, and two community nurses. METHOD: In-depth interviews with a maximally varied purposeful sample of patients, caregivers, and providers were analyzed using immersion and crystallization techniques. MAIN FINDINGS: Findings revealed the potential for enhanced continuity of care and interdisciplinary team functioning. Having a nurse practitioner, interdisciplinary team-building exercises and meetings, regular face-to-face contact among all providers, support for family caregivers, and 24-hour coverage for physicians were found to be essential for success. CONCLUSION: Integration of services takes time, money, and sustained commitment, particularly when undertaken in geographically isolated communities. Informed choice and a fair remuneration system remain important considerations for family physicians. PMID- 11785282 TI - Identifying and slowing progressive chronic renal failure. AB - OBJECTIVE: To help inform primary care physicians about how to identify and slow progressive chronic renal failure. QUALITY OF EVIDENCE: The National Library of Medicine (1996 to 2000) was searched using PubMed with search terms pertinent to studies on identification, course, and management of chronic renal failure. References in retrieved papers and older literature known to the authors supplemented the searches. In general, sufficient high-quality studies, systematic reviews, or guidelines based on such evidence were available to support our main points. MAIN MESSAGE: End-stage renal disease (ESRD) poses a large and growing morbidity, mortality, and financial burden. Almost all patients reach ESRD as a result of chronic progressive conditions, particularly diabetic nephropathy, hypertensive-vascular renal disease, and glomerular disorders. Patients at risk merit regular renal assessment with serum creatinine tests and urinalysis. Persistent high blood pressure and heavy proteinuria are the strongest predictors of progression of chronic renal failure. Patients with renal disease should be examined and treated for vascular disease and vice versa. Blood pressure lowering, ACE inhibition, and avoidance of further renal insults (such as use of nephrotoxins) can slow the decline of renal function. Restricting dietary protein has a weak effect on slowing renal failure and is not easy to apply in primary care. Timely involvement of specialized nephrology teams is important. CONCLUSION: Family physicians play an important role in recognizing patients with potential for renal failure, in demonstrating progressive chronic renal failure, and in initiating therapy early to improve outcomes. PMID- 11785284 TI - [Mobile genetic element MDG4 (gypsy) in Drosophila melanogaster. Features of structure and regulation of transposition]. AB - Distribution of two structural functional variants of the MDG4 (gypsy) mobile genetic element was examined in 44 strains of Drosophila melanogaster. The results obtained suggest that less transpositionally active MDG4 variant is more ancient component of the Drosophila genome. Using Southern blotting, five strains characterized by increased copy number of MDG4 with significant prevalence of the active variant over the less active one were selected for further analysis. Genetic analysis of these strains led to the suggestion that some of them carry factors that mobilize MDG4 independently from the cellular flamenco gene known to be responsible for transposition of this element. Other strains probably contained a suppressor of the flam- mutant allele causing active transpositions of the MDG4. Thus, the material for studying poorly examined relationships between the retrovirus and the host cell genome was obtained. PMID- 11785283 TI - Office management of elderly hypertensive patients. Focusing on cognition and function. AB - OBJECTIVE: To review office management of elderly hypertensive patients and to focus on cognition and function both as ways to stratify who gets treated and as end points for treatment. QUALITY OF EVIDENCE: Relevant papers were identified through a MEDLINE search from January 1994 to March 2000, using the MeSH terms hypertension, aged, aged 80 and over, cognition, activities of daily living, therapeutics, hypotension orthostatic, and dementia. Many well conducted randomized controlled trials were found and are included. MAIN MESSAGE: Treatment of combined and systolic hypertension up to age 80 is clearly worthwhile; beyond age 85, other factors (chiefly cognitive and functional impairment) mitigate most routine recommendations. Successful treatment is individualized, taking into account comorbid conditions and their effect on cognition and function. Age is useful for thinking about groups, not individuals: as people age, risk of cognitive and functional impairment increases, but even very elderly people (> 85 years) with no impairment should be treated as younger patients are. Elderly people with signs of having a "brain at risk" should be managed with special vigilance. CONCLUSION: Good evidence supports treating elderly people, who are otherwise well and are cognitively and functionally intact, when their blood pressure is > 160 mm Hg systolic or > 105 mm Hg diastolic. There is insufficient evidence for carrying out routine recommendations for frail elderly people. Treatment of comorbid illnesses dictates choice of therapeutic agent. PMID- 11785285 TI - [High frequency conjugative mobilization in natural strains of Bacillus subtilis, bearing a large plasmid]. AB - Conjugative properties of the strain Bacillus subtilis that carrying a large plasmid approximately 95 kb in size and isolated in Belarus from forest soil were described. The staphylococcal plasmid pUB110 that had previously been introduced into this strain was transferred to recipient cells of the Bacillus subtilis 168 strain with a frequency of approximately 10(-2). The transfer occurred with approximately the same frequency both upon donor and recipient cell contact on the surface of membranes and in a liquid medium. The latter fact makes this system suitable as a model for studying conjugal mobilization in bacilli. A large plasmid cannot be transferred to recipients. An optimal temperature for conjugation of donor and recipient cells was 37 degrees C, but conjugation also proceeded at lower temperatures, up to 21 degrees C. PMID- 11785286 TI - [The effect of some mutations in the Trl gene on mitosis in embryonal and larval tissues and egg chamber morphology in Drosophila melanogaster]. AB - A study was made of three insertional mutations (Trl13C, Trls2325, and TrlEP(3)3184) located in the second intron of the Trithorax-like (Trl) gene for the GAGA transcription factor (GAF). Their cytological effects were analyzed in oogenesis, early embryonic development, and in larval development (96-108 h) in cells of nervous ganglia and imaginal disks. Notwithstanding an interallelic difference in expression, all three P-element insertions proved to be dominant as far as the examined parameters were concerned. The most substantial defects were the formation of "granular" chromatin during the interphase and mitosis and high proportions of cells with hypercondensed chromatin (which were arrested at the G2/M boundary) and cells with abnormal chromosome segregation. A higher frequency of egg chambers with trophocytes defective in number and in chromatin condensation was observed in females carrying the mutant Trl gene. The defects were assumed to result from poor coordination of the chromosome and cell cycles and, including, the nuclear and centrosomal cycles in embryonic development and the cycles of chromosome condensation and spindle formation in cells of larval imaginal disks and nervous ganglia. PMID- 11785287 TI - [Phase-specific elements of the regulatory zone of the Drosophila melanogaster string gene]. AB - The phases of the reporter gene expression controlled by different fragments of the string (stg) gene regulatory region were determined in Drosophila neuroblasts by detection of beta-galactosidase activity and radioautography. In the D10 and D22 lines carrying the constructs pstg beta-E4.9 and pstg beta-E5.3, respectively, the reporter gene activity was detected in the G1 phase of the cell cycle. In the D12 and D20 lines (pstg beta-E6.4 and pstg beta-E2.6), no periodic expression was observed. The regulatory regions of the stg from lines D10 and D22 and that of Drosophila gene cyclin D shared consensus aagaactttg, which was also expressed in the G1 phase. The phase-specific expression of the cell-cycle genes was compared in a model for the mitotic-wave cells of eye imaginal disk and neuroblasts of the nerve ganglia. PMID- 11785288 TI - [Genetic screening of meiotic mutations in mosaic clones of the Drosophila melanogaster female germline]. AB - A method of screening for meiotic mutations based on genetic analysis of chromosome disjunction in germline mosaic clones of females homozygous for potential mutations is proposed. The clones are obtained at high frequency due to the use of the transgenic FLP/FRT system of mitotic recombination. This system permits obtaining homozygous clones in the first generation after mutagenesis, whereas the cultures are set up after selection for potential meiotic mutations. This significantly enhances, the efficiency of screening by the elimination of the limiting stage. Using this method, the following mutations were revealed in the 3L arm of Drosophila: ff6 leading to disturbed centriole disjunction, which results in appearance of multi-tail spermatids and three-pole spindles during male meiosis; ff3 leading to the formation of chromosome bridges in anaphase and telophase, chromosome nondisjunction, and premature chromatin condensation after metaphase; embryonic lethal ff29, with disturbed coordination between nuclear and centrosome cycles during syncytial cleavage; and a series of other mutations causing a wide spectrum of disturbances in male meiosis. Comparison of the proposed method with procedures of screening for yeast cell-cycle mutations showed that we succeeded in attaining the efficiency of screening in the Drosophila model close to that in the yeast model. PMID- 11785289 TI - [Interline differences in morphology of the precentromeric region of polytene X chromosome in Drosophila melanogaster salivary glands]. AB - Morphology of the Drosophila melanogaster polytene X chromosome section 20 in normal flies, in strains carrying inversions that break pericentric heterochromatin at different points, and at the background of the Su(UR)ES mutation has been examined. In all of the strains carrying the Su(UR)ES mutation section 20 displayed a distinct banding pattern till to the section 20F, while in the wild-type strains this region was represented by beta-heterochromatin. The strains carrying different inversions substantially differed in the number and morphology of bands forming section 20. In the Su(UR)ES mutants the most proximal X chromosome euchromatin gene, su(f), is mapped to the boundary between sections 20E and F, while rDNA forming the middle part of the X chromosome mitotic heterochromatin is located in the proximal part of section 20F. All large bands observed in section 20 of the w; Su(UR)ES strain were also present in In(1)sc4; Su(UR)ES, which breaks heterochromatin in the distal part. Hence, the bands of polytene chromosome section 20 are virtually devoid of mitotic heterochromatin. PMID- 11785290 TI - [Use of matroclinous haploid plants in recurrent selection in corn]. AB - Two cycles of recurrent selection were performed in maize with the use of matroclinous haploids. Two synthetic populations, SP and SA, were improved. Each cycle consisted of two stages: (1) isolation of haploids from the synthetic populations and (2) growth of the haploids, pollination with pollen from diploid plants, and selection. The selection was performed for ear size in haploid plants. The mean gain in productivity in the synthetic populations SP and SA the per cycle was 16.48 and 20.98%, respectively. It is suggested that the high value of this index is related to the fact that haploid plants reveal useful genes with additive and epistatic effects. Natural selection may have played a part, too. The combination of artificial and natural selection in haploids resulted in a considerable gain in productivity in the synthetic populations to be improved. PMID- 11785291 TI - [Mutagenic effect of nitrosomethylurea, modified by heat shock at early stages of sunflower seedling development]. AB - A comparative study of chlorophyll mutations induced in sunflower seedlings of the initial line 3629 and its nuclear and plastom mutant derivatives by nitrosomethylurea (NMU) (0.015%), heat shock (HS, 40 degrees C), and their combination was performed. The spectrum and frequency of chlorophyll mutations depended on the treatment conditions and on the genotype of the lines tested. Nuclear mutant displayed highest sensitivity to NMU, HS, and their combination. The line 3629 plants displayed highest tolerance to NMU and HS. However, plastom mutants were more tolerant to the combination of the mutagens compared to the plants of the initial line. PMID- 11785292 TI - [Genetic diversity in a small population of sockeye salmon, Oncorhynchus nerka (Walbaum) from the Ola river (northern coast of the Okhotsk sea)]. AB - The genetic structure of a small sockeye salmon population from the Ola River (Tauyskaya Inlet, the Okhotsk Sea) was shown to exhibit high heterogeneity. Significant differences of LDH-B2* and ALAT-2* gene frequencies were detected not only among samples within the spawner and juvenile groups but also between spawners and juveniles as a whole. The average heterozygosity of sockeye salmon from the Ola River was considerably lower than the corresponding values for other Asian populations. The Ola sockeye salmon is genetically similar to the population from the Pakhach River of the northwestern Kamchatka Peninsula but different from other Kamchatka populations and the Okhota River population. A hypothesis explaining the genetic differentiation of Asian sockeye populations is advanced. PMID- 11785293 TI - [Comparison of mitochondrial DNA in two greenling species and their hybrids (CEM. Hexagrammidae: Pisces) from Peter the Great Bay (Sea of Japan)]. AB - Fragments of mtDNA from two greenling species, Hexagrammos octogrammus and H. agrammus, and their possible hybrids were amplified in PCR and examined using RFLP analysis. The inferred sequence difference between the species was 6.6%, which corresponds to about 3 Myr of their divergence. The reproductive contribution of males and females to the hybrids was estimated. PMID- 11785294 TI - [Eight polymorphic blood protein systems in Arab horses from Turkey]. AB - Analysis of the blood protein system was used to study the genetic composition of Arabian horses. Biochemical markers of eight polymorphic loci (Tf, Al, Es, AlB, Gc, Hb, PGD, and PGM) were electrophoretically identified in blood samples. A total of 43 phenotypes were identified for these polymorphic systems. The Tf, Hb, and Es loci appeared to be more polymorphic than the other loci studied. Statistically significant differences between the observed and expected genotypic frequencies were found for the PGD and PGM loci (P < 0.05 and P < 0.01, respectively). Individual allele frequencies, observed and expected phenotype frequencies, and the average heterozygosity were estimated for each polymorphic locus. PMID- 11785295 TI - [Analysis of heterozygosity levels at P1,TF, PGM1, ACP1, HP, GC, GLO, C3, and ESD loci in pulmonary tuberculosis patients with different treatment outcomes]. AB - Heterozygosity at nine genetic loci (PI, TF, PGM1, ACP1, HP, GC, GLO1, C3, and ESD) was analyzed in pulmonary tuberculosis patients with good (group 1, N = 71) and poor (group 2, N = 35) response to treatment. The observed heterozygosities were compared with the expected values, which were calculated from allele frequencies in a control sample of healthy individuals (N = 328 with all but one locus and 78 with ESD) according to Hardy-Weinberg expectations. The analysis showed that the observed heterozygosities gl of patients significantly differed from the expected values hl in the case of four loci (GC, PI, C3, and ACP1). The observed heterozygosity was higher than expected in three cases (PI, C3, and ACP1) and lower then expected (GC) in one case. When data on each individual locus were compared using Fisher's exact test, both groups of patients proved to significantly differ (PF < 0.05) from the control group in the same four loci. No difference in observed heterozygosity was detected between the two groups of patients. The mean expected heterozygosity was h = 0.386 +/- 0.00674; the mean observed heterozygosity was g = 0.415 +/- 0.02 in group 1, g = 0.402 +/- 0.026 in group 2, and g = 0.371 +/- 0.00955 in the control group. The t test did not reveal a significant difference between the mean values of expected observed heterozygosities. Heterozygosity at individual loci, rather than mean heterozygosity, was proposed as an integral nonspecific indicator of the genetic control of a disease, because the former directly implicates individual marker loci in the development of a disorder, whereas effects of individual loci may eliminate each other when mean heterozygosity is computed. Based on the results obtained, a genetic control was assumed for the development of the tuberculosis process in the lungs. PMID- 11785296 TI - [Search for frequently encountered mutations in genes predisposing to breast cancer]. AB - DNA of oncological patients, including Ashkenazi Jews and Slavs, living in St. Petersburg was collected, and the resultant collection was screened for three common mutations of genes BRCA1 and BRCA2 by means of heteroduplex analysis. The mutation 5382insC in exon 20 of the BRCA1 gene was found in four unrelated patients, including three Slavs and one Ashkenazi Jew, with a positive family history of breast cancer. The mutations 185delAG and 6174delT in the BRCA1 and BRCA2 genes, respectively, which are typical of Ashkenazi Jewish patients with breast cancer, were not found in the patients of either ethnicity living in St. Petersburg, although the 6174delT mutation was found in the control group of Ashkenazi Jews. A new 12-nucleotide duplication g.71741ins12nt found in intron 20 of the BRCA1 gene was described. The high frequency of the 5382insC mutation in the BRCA1 gene in patients with familial breast cancer in both St. Petersburg and Moscow indicates that Russian families with the history of breast cancer should be primarily tested for this mutation. PMID- 11785297 TI - [Analysis of genetico-demographic structure of rural populations living near the Semipalatinsk nuclear test site]. AB - Rural populations neighboring the Semipalatinsk nuclear test site were used as a model to develop and test an integrated population-genetic approach to analysis of the medical genetic situation and environmental conditions in the areas studied. The contributions of individual factors of population dynamics into the formation of the genetic load were also assessed. The informative values of some genetic markers were estimated. Based on these estimates, a mathematical model was constructed that makes it possible to calculate numerical scores for analysis of the genetic loads in populations differing in environmental exposure. PMID- 11785298 TI - [Frequency, dynamics, and structure of congenital malformations in populations under long-term exposure to ionizing radiation]. AB - Information on the dynamics, frequency, and structure of congenital malformations (CMs) and chromosomal diseases in two generations of rural populations from the Semipalatinsk region was obtained for the first time. The tests performed in the Semipalatinsk nuclear test site (STS) for many years were demonstrated to deteriorate the genetic health of the populations of the zones of extreme and maximum radiation risks. Mutagenic and teratogenic effects of long-term ionizing irradiation were detected. These were mainly expressed as an increase in the frequencies of strictly registered CMs (SR CMs), including the Down syndrome, multiple malformations (MMs) and microcephaly (1.45 +/- 0.11, 1.39 +/- 0.01, and 0.77 +/- 0.05 per 1000 births, respectively). SR CMs exhibited linear trends toward higher frequencies in two generations of exposed persons after surface nuclear tests in 1949-1963. Their frequency was strongly correlated with the effective population dose of radiation; the main population genetic parameters (inbreeding coefficient, endogamy index, etc.) had less pronounced effects on Cms. PMID- 11785299 TI - [Differentiation of Slavs and their genetic position among Eurasian peoples from data on mitochondrial DNA diversity]. AB - The distribution of identical and similar (phylogenetically related) types of hypervariable segment 1 (HVS1) of the mitochondrial DNA (mtDNA) was studied in human populations belonging to three Slavonic groups and nine ethnogeographic groups of Eurasia (total sample size 2772 people). The results testified to a common origin of West, South, and East Slavs and revealed a central place of West Slavs among all Slavonic ethnoses. Mixing was shown to play a substantial role in the formation of specific features of all three Slavonic gene pools. The mitochondrial gene pools of the Slavonic ethnoses proved to preserve features suggesting a common ancestor for these and South European populations (especially those of the Balkan Peninsula). PMID- 11785300 TI - [Differences in allele frequency at the BAIB locus, determining the level of expression of beta-aminoisobutyric acid, in healthy donors and coronary artery atherosclerosis patients from Buryat and Lithuanian populations]. AB - Phenotype and allele frequencies of the genetically dimorphic system determining urinary excretion of beta-aminoisobutyric acid (BAIB) were studied in population samples of Buryats from the Aginskii Buryat Autonomous District and Lithuanians from Vilnius and in patients with coronary atherosclerosis (CA) from both populations. Frequency of allele BAIB*b, which determines high BAIB excretion, proved to be more than twice higher in Buryats compared with the population sample of Lithuanians (0.620 versus 0.289, respectively). The proportion of individuals with high BAIB excretion in CA patients of either ethnic sample was twice higher than in the corresponding control sample. Frequency of allele BAIB*b in CA patients and healthy individuals was 0.348 and 0.242, respectively, in the Lithuanian population and 0.775 and 0.557, respectively, in the Buryat population. Thus, assessment of urinary excretion of BAIB proved to be prognostically valuable. The method used to detect a variation in BAIB excretion is relatively inexpensive, simple, and suitable for mass screening of patients and healthy individuals (population control). After additional testing with representative samples, the method can be used as an accessory diagnostic test in patients with cardiovascular disorders. PMID- 11785301 TI - [Study of two species of mussels, Mytilus trossulus and Mytilus galloprovincialis (Bivalvia, Mytilidae) and their hybrids, using PCR markers, in Peter the Great Bay of the Sea of Japan]. AB - Bivalve mollusks of the genus Mytilus (M. trossulus and M. galloprovincialis) occurring in Peter the Great Bay of the Sea of Japan were first studied in Russia. A region of nonrepetitive sequences of the gene encoding the polyphenolic adhesive protein bissus was used as a species-specific genetic marker. After amplification using specific primers, a 126-bp fragment was found to amplify in all representatives of M. galloprovincialis collected from driftwood in the gulf Posset (the southwestern part of Peter the Great Bay). M. trossulus specimens from the same region were shown to have a 168-bp fragment. In Vostok Gulf (the eastern part of Peter the Great Bay), both artificially grown mussels and those from natural habitats contained a 168-bp fragment or two fragments (126- and 168 bp) that corresponded to a hybrid form between the above species. The possibility of using this genetic marker to identify closely related Mytilus strains and their hybrids in similar habitats, near the Primorye coast in particular, was demonstrated. The presence of approximately 9% of hybrid specimens confirms that a zone of hybridization between M. trossulus and M. galloprovincialis may exist in this region. PMID- 11785302 TI - [Localization of DNA probes for human ribosomal genes on barley chromosomes]. AB - To estimate the possibility of plant genome mapping using human genome probes, the probes fluorescent in situ hybridization (FISH) of human 18S-28S rDNA (clon 22F9 from the LA-13NCO1 library) was carried out on chromosomes of the spring barley Hordeum vulgare L. As a control, wheat rDNA probe (clon pTa71) was taken. Hybridization of the wheat DNA probe revealed two major labelling sites on mitotic barley chromosomes 5I (7H) and 6I (6H), as well as several minor sites. With the human DNA probe, signals were detected in the major sites of the ribosomal genes on chromosomes 5I (7H) and 6I (6H) only when the chromosome preparations were obtained using an optimized technique with obligatory pepsin treatment followed by hybridization. Thus, this study demonstrates that physical mapping of plant chromosomes with human DNA probes that are 60 to 75% homologous to the plant genes is possible. It suggests principal opportunity for the FISH mapping of plant genomes using probes from human genome libraries, obtained in the course of the total sequencing of the human genomes and corresponding to the coding regions of genes with known functions. PMID- 11785303 TI - [Aluminum induces chromosome aberrations in wheat root meristem cells]. AB - The yield and pattern of chromosome structure aberrations in wheat seedlings treated with aluminum nitrate and aluminum sulfate at various concentrations have been determined by the anaphase method. Aluminum has a genotoxic effect causing genome, chromatid, and chromosome aberrations in apical root meristem cells. The relationship between the total yield of structural mutations and the aluminum concentration follows a bell-shaped curve. The mutagenic activity of aluminum nitrate peaks at 10(-3) mg/ml, which is twice as high as the permissible concentration limit (PCL) of aluminum in potable water. The maximum of the mutagenic activity of aluminum sulfate is observed at 5 x 10(-4) mg/ml, i.e., one PCL. Tap water boiled for 2 h in an aluminum vessel has virtually no genotoxic effect on wheat cells. PMID- 11785304 TI - [Allelopathic activity of volatile secretions in irradiated animals]. AB - In the period of the most expressed postirradiation (4 Gy) injury, the rats secreted volatile components capable of lowering the blood cells count in intact rats. This ability of the irradiated animals is not strictly specific for species since the depression effect on rats is exerted also by volatile components of irradiated mice. We suggest marking this phenomenon as postirradiation allelopathy. PMID- 11785305 TI - [Role of apoptotic cell death in radioinduced aging in Drosophila melanogaster]. AB - The attempt in made to estimate a role of programmed cell death (apoptosis) in radio-induced life span alteration and aging. It was shown with the use of mutant Drosophila melanogaster laboratory strains, that the disfunction of a reaper dependent apoptosis pathway, together with the action of ionizing radiation and/or apoptosis inductor etoposide, could lead to change of life span and a pace of aging. In Drosophila strain with defect of proapoptosis gene reaper, the increase of life span after irradiation and etoposide treatment was observed. At the same time the strain with overexpression of a protease dcp-1 gene and the strain with the defect of antiapoptosis diap-1/th gene decreased the life span after irradiation and etoposide treatment. The obtained facts are discussed from a position of participation of apoptosis deregulation in radio-induced and natural aging of whole organisms. PMID- 11785306 TI - [Study of the radioprotective effect of the NO-synthase inhibitor L-NAME in Chinese hamster cell culture]. AB - A radioprotective effect of L-NAME was estimated by the yield of the aberrant anaphases after exposure of Chinese hamster cells to different doses of gamma rays and beta-particles. It was shown that cell treatment with L-NAME before irradiation only decreased the frequency of radiation-induced chromosome aberrations. The equal yield of the aberrant anaphases was found in the cells treated with L-NAME and irradiated with 6 Gy gamma-rays later and in the cells non-treated with L-NAME and irradiated with 3 Gy gamma-rays. The treatment of cells with L-NAME just before and immediately after irradiation did not modify the radiation-induced frequency of the chromosome aberrations. The treatment of cells with L-NAME decreased the level of SH-groups (as estimated by UV spectrophotometer) and increased the chromatin condensation (as estimated by flow cytometry). It was suggested that radioprotective effect of L-NAVE may be connected with its cooperation with DNA. Condensation of L-NAME on the surface of DNA resulted in increasing of probability of the chemical repair of DNA-radicals after irradiation. Thus, these results indicate the involvement of NO-dependent mechanism of the realization of the radiation-induced damage to the hereditary cell structure and optimal conditions for the realization as well as the conceivable mechanism of radioprotective effect one of the most inhibitors of NO synthase--L-NAME. PMID- 11785307 TI - [Effect of protein kinase C and NO-synthase inhibitors on the radiation-induced cytogenetic adaptive response in cultured Chinese hamster cells]. AB - The effects of the serin-threonin kinase inhibitor--staurosporin and inhibitor of NO-synthase--L-NAME on the radiation-induced adaptive response were studied in fibroblasts of Chinese hamster in culture. We have shown that the adaptive response as measured by the reduction of radiation-induced chromosome aberrations was completely blocked in the presence of staurosporin as well as L-NAME. These inhibitors themselves did not increase the chromosome aberration frequency when cultures were irradiated with 3 Gy alone in the presence of inhibitors. Furthermore, L-NAME noticeably decreased the gamma-rays-induced level of the chromosome aberrations. Our study confirms the participation of protein kinase C in the induction of the adaptive response and first indicates the participation of NO-synthase in this response. PMID- 11785308 TI - [Photoprotective properties of melanins from grape (Vitis vinifera) and black tea (Thea sinensis)]. AB - Dark pigments of melanin type were extracted from the rind of ripe grapes Vitis vinifera (ring "Alfa") and pack tea (Thea sinensis). The study of photoprotection activity of the extracted pigments have shown that they intensively absorb radiation in the UV and visible. The increase of the photoprotection effect correlates with the concentration of paramagnetic centers in the melanins. The pigments reduce the number of damaged molecules of plasmid DNA pBR-322 and inhibition the IUV-induced lipid peroxidation. PMID- 11785309 TI - [Increase in the level of metallothioneins in mouse liver after administration of cadmium chloride does not protect from combined radiation-thermal injury]. AB - Effects of MT preinduction by cadmium chloride on the resistance to combined injury such as whole body gamma-irradiation at the dose of 7 Gy + thermal burn were investigated in (CBA x C57BL6)F1 mice. Normal level of MT markedly increased in mice liver but not in bone marrow cells if Cd was given subcutaneously (1 mg/kg) prior to combined injury. However, preinduction of MT did not reduce the lethal effects and bone marrow devastation caused by combined radiation injury. No differences in the leukopenia degree and in CFU-s number were observed between control and MT-induced mice. In summary, Cd-induced MT elevation in mice liver does not protect against the toxic and lethal effects caused by combined radiation injury. PMID- 11785310 TI - [Stability of model solutions of organochlorine pesticides under the effect of gamma-radiation]. AB - The effect of concentration (0.01; 0.1; 1 ppm), polarity of solvent (hexane and 2 propanol), dose rate of gamma-irradiation (0.026; 0.042; 0.14 kGy/min) on a radiation degradation degree of organochlorinated pesticides (OCP) is discussed in this article. The conditions of maximal degradation of model solutions of OCP under gamma-irradiation are determines, based on the results obtained. PMID- 11785311 TI - [Effectiveness of measures directing to lowering the dose of radiation to residents of rural settlements in the extended period after the accident at the Chernobyl atomic energy station]. AB - Justification of the application of countermeasure options in the long term after the Chernobyl accident is presented exemplified by a number of rural settlements located in areas with different fallout density. Protective and rehabilitation countermeasures are ranked based on the criterion such as cost of 1 man.-Sv. Estimated are time periods when the need in countermeasures will persist for settlements located in areas with different contamination levels and internal dose contribution to the overall dose. PMID- 11785312 TI - [Effect of some natural processes on the formation and characteristics of aerosols in regions polluted with radionuclides]. AB - The formation of aerosols over the radioactive polluted areas results from some natural and industrial factors. In this paper physico-chemical characteristics of secondary aerosols generated by the Chernobyl accident are presented. The results of monitoring of the aerosol from traffic, dust storms and forest fires in 30-km zone of the Chernobyl nuclear power plant and other regions are compared. Some methodical aspects of the sampling and analyses of aerosols are considered. The recommendations for choice of the personal respirators are given. PMID- 11785313 TI - [Pulse flows of cortical neuron populations exposed to microwaves: interspike intervals]. AB - In unanesthetized nonimmobilized rabbits pulse flows of populations of cortical neurons were investigated prior, during, and after 1-min microwave irradiation (wavelength 37.5 cm, power density 0.2-0.3; 0.4; 0.5; and 40 mW/cm2). Changes of interspikes intervals occurred through these exposure. Shifts as the decrease of mean values of interspike intervals predominated under irradiation of 0.2-0.3 and 0.4 mW/cm2. Shifts of the opposite direction prevailed under irradiation of 0.5 and 40 mW/cm2. The least changes of the interspike intervals took place under irradiation of 0.4 mW/cm2. PMID- 11785314 TI - [Electromagnetic components of a modern urbanized environment]. AB - The investigations of intensity of electromagnetic field in the range of frequencies 30 MGz-300 GGz were carried out in Tomsk. The percentage contribution of every frequency subrange in to total intensity electromagnetic field of Tomsk was estimated. So for frequency range 30-100 MGz it corresponds to 4.3%; for 100 200 MGz--7.4%; for 200-300 MGz--4.6% and 300 MGz-300 GGz corresponds to 83.7%. Thus, the investigations of a level of electromagnetic field of an anthropogenous origin allowed estimation of the integrated level of electromagnetic field in the range of frequencies 30 MGz-300 GGz and construction of the spatial distribution of an electrical component of the field, and also revealing the basic sources of electromagnetic pollution. PMID- 11785315 TI - [Thermocompensatory reactions of rabbits in response to microwave irradiation at different environmental temperatures]. AB - Thermogenic effectiveness of electromagnetic irradiation (EMI) of UHF range (7 GHz) in the dependence on intensity (10-100 mW/cm2) and environmental temperature was studied in experiments with rabbits. Synergistic interaction of EMI and high ambient temperature was established. The existence of optimal EMI and high ambient temperature was established. The existence of optimal EMI intensity at which the synergy was maximal was shown. It is concluded that this interaction should be taken into account for hygienic standardization of nonionizing EMI. PMID- 11785318 TI - Keeping our patients pedaling--one unit's experience. AB - Ask yourself, if you could take a pill to increase your energy level, muscle mass, bone strength and decrease cardiovascular risk, would you? Exercise on dialysis could be that pill. The purpose of an exercise program is to provide a holistic approach to care, enabling patients to shift their focus from sick to well, to be the best they can be. The benefits of exercise include improved quality of life, and an interruption of the downward spiral of deconditioning which leads to inactivity and disability (Painter, 1995) These benefits have been well documented by Patricia Painter, PhD, and the London Health Sciences Centre, London, Ontario (Ridley, Hoey, Ballagh-Howes, 1999). In 1999, our vision of an in centre hemodialysis exercise program became a reality. Now, one year after implementation, keeping patients motivated and staff committed to participate in this effective program has become our latest goal. PMID- 11785319 TI - Managing peritoneal dialysis prescriptions. AB - Current literature (Blake et al., 1996) suggests prescribing peritoneal dialysis based on individual characteristics and a sound knowledge of factors known to improve clearances. According to the CANUSA study (1996), better clearances are associated with a decreased relative risk of death, a decreased relative risk of technique failure and decreased hospitalization. This article will discuss factors which will improve clinical practice by prescribing peritoneal dialysis on an individualized basis leading to optimal patient outcome. PMID- 11785321 TI - The nursing shortage in nephrology: the reasons and the impact. PMID- 11785320 TI - [Self-care guide for dialysis patients--an essential tool]. AB - The initial production of a poster and a document about a Hepatitis B vaccination protocol spurred the further development of a self-care guide for dialysis patients. The Hepatitis B vaccination document, which was an important tool for recording vaccination results, gave rise to a completely unexpected development. Based on feedback from the patients, all dialysis results eventually became integrated into a self-care guide. In this self-care guide, not only is general information for dialysis patients provided but also specific advice to promote continuity of care. Nurses play an important role in encouraging and developing the self-care abilities of patients. With case management, the nurse also plays an important role in health promotion for a group of patients. There are countless benefits for the targeted group. This self-care guide is intended to be a tool to provide information, to promote awareness, to aid follow-up and to prevent complications. Its goal is an improved state of health and wellbeing for dialysis patients. PMID- 11785322 TI - On education--developing a hemodialysis orientation. PMID- 11785323 TI - Meeting the challenges of writing effective patient print material. AB - End stage renal disease patients and families need ongoing education to help them cope and adapt to their illness. As nephrology nurses, you would use patient print material as a tool in your comprehensive patient teaching program. Print material allows the patient or family member to refer to learned material at any time after the formal teaching session. Developing effective print material can be daunting, but if you follow this article's stepwise approach, it can be rather simple. This article will discuss steps you can take to ensure the content is relevant to your intended audience, how to arrange the content to captivate readers' attention, how to organize the content to make it easier for the reader to read. The readers are then likely to memorize the material. PMID- 11785324 TI - The Kool Kidney: an educational program for school-aged children. AB - With the increasing prevalence of renal failure and increasing demands on the health care system for renal replacement therapies, we felt a program to promote early education on kidney disease with strategies to prevent kidney failure was much-needed. The Kool Kidney project is an educational tool developed to help educate grade five students on the basic anatomy and physiology of the normal healthy kidney. The project is based upon some theory discussion as well as some "hands-on" fun. In a typical presentation, a nephrology nurse or nurses will go into the classroom and discuss the kidney. The presentation is broken down into three major parts: PART ONE: Has the presenter discuss the normal basic anatomy of the kidney as well as a simplistic overview of the function of the kidney. PART TWO: Is a brief discussion of the realities of kidney failure in language understood by children, as well as a discussion on dialysis, both hemo and peritoneal, and transplantation. PART THREE: Is the fun part. In this segment the children are allowed to come up and get some hands-on experience. We have harvested some kidneys from pigs and had them dissected and preserved by the lab at our hospital. The children are allowed to pick up and examine a kidney. To date we have presented the "Kool Kidney" to six schools and approximately 200 students. The presentations have been a fun learning experience for the students and the presenters. It is hoped that if we can alert one child to a potential renal complication and have the child seek medical attention early, or if we can prevent one unnecessary injury, the program will have been a total success. PMID- 11785325 TI - Keep it simple! A touch technique peritoneal dialysis procedure for the blind and visually impaired. AB - Diabetes is the main cause of blindness in patients with end stage renal disease (ESRD). The number of diabetic patients who require dialysis has increased from 16% in 1981 to 30% in 1999 (CIHI, 1999). Therefore, it is important for blind individuals to find a peritoneal dialysis (PD) technique that will ensure their independence and prevent peritonitis. In July 2000, the home peritoneal dialysis unit (HPDU), Toronto Western Hospital (TWH), University Health Network, successfully developed and implemented a "touch technique" connection procedure for the blind and visually impaired. The procedure involved is a touch technique connection utilizing the Fresenius Premier Plus Double Bag system. Three blind patients on the UV Flash peritoneal dialysis system were retrained in the touch technique on a one-to-one basis for an average of four days. Additionally, they were each given a procedural audiotape or CD for reference at home. This simple touch technique has enabled these three patients the freedom of a relatively independent lifestyle. They have been peritonitis-free since implementation, for 19, 15 and four months respectively. This technique allows blind and visually impaired ESRD patients to perform peritoneal dialysis in their homes and, thus, maintain independence. PMID- 11785326 TI - On education--the preceptor in hemodialysis orientation. PMID- 11785327 TI - Results of the study of the certified workforce. PMID- 11785328 TI - [Vibrovacuumometry--a new method of treating spinal osteochondrosis]. PMID- 11785329 TI - [Use of a program of medical and psychological support in patients with ischemic heart disease, having undergone aortocoronary shunting]. AB - 167 patients with aortocoronary bypass were treated in the sanatorium ("Arkhangelskoye") and then for a year were treated outpatiently. Of them, 127 patients have additionally undergone training according to the program of medical and psychological rehabilitation. 40 control patients have not been trained. Learning went on at the sanatorium in different groups of psychotherapy. It is shown that the above psychotherapy raises motivation to patient's compliance, psychoregulation and self-control. This improves quality of life and encourages patients to resume jobs. PMID- 11785330 TI - [A possible mechanism of the hypotensive effect of laser irradiation in patients with ischemic heart disease with arterial hypertension]. AB - 93 patients with ischemic heart disease, 44(47.3%) of them with arterial hypertension, were exposed to laser irradiation (LI). LI was accompanied with lowering of arterial pressure, more prominent in hypertensive patients. Mechanism of the hypotensive effect of laser therapy operates largely through stabilization of the lipid bilayer of the cell membrane demonstrated on the model of erythrocyte. PMID- 11785331 TI - [Possibility of using intensive peloid balneotherapy on duodenal ulcer patients]. AB - The authors studied effectiveness of intensive peloidobalneotherapy (PBT)--daily peloids, baths and drinking mineral water--in 124 patients with duodenal ulcer in attenuating exacerbation and incomplete clinical remission. The condition of the gastroduodenal zone was studied with intragastric pH-metry, esophagogastroduodenoscopy with spot biopsy, usease test, rheohepatography. Intensive PBT reduced the time of the treatment by 8-10 days, faster relieved clinical symptoms, raised the number of ulcer healings, normalized acid function of the stomach, prolonged long-term effect. The response of the body to intensive PBT increases therapeutic effectiveness 1.6 times. Tolerance criteria for PBT and the effect prognosis formula have been designed. PMID- 11785332 TI - [Effect of chloride-hydrocarbonate sodium mineral water Rychal-Su on some physiological and biochemical indicators of the liver in rats with experimental toxic hepatitis]. AB - Rats with tetrachlormethan-induced toxic hepatitis were given mineral water Rychal-Su from the spring in Dagestan. Investigation of some physiological and biological parameters has shown that Ry-chal-Su mineral water has a hepatoprotective action, in toxic hepatitis improves protein spectrum in the serum, inhibits transaminase activity and accumulation of malonic dialdehyde in the liver, improves excretory and antitoxic functions. PMID- 11785333 TI - [Effect of therapeutic complexes using contrast baths, ultrasound and electric stimulation on anthropometric indicators and carbohydrate metabolism in patients with exogenous-constitutional obesity]. AB - Contrast baths proved effective in reducing obesity as they influence body weight index, waist and hip circumferences, improve carbohydrate metabolism, lower insulin resistance. Ultrasound plus contrast baths complex is more effective in hynoid obesity while contrast baths plus electrostimulation with SMC is good in abdominal obesity. PMID- 11785334 TI - [Theoretical and practical aspects of general magnetotherapy]. AB - Such aspects of general magnetotherapy as grounds, mechanisms of physiological and therapeutic action, facilities, application, recommendations, perspectives are reviewed. PMID- 11785335 TI - [Combined use of drinking mineral water and the natural enterosorbent zosterine in kidney stones (an experimental study)]. AB - A combined action of carbonic mineral waters of Shmakovsky and Mukhensky deposits and natural enterosorbent zosterin was studied in nephrocalcinosis in experiment. Taking carbonic mineral waters reduced intoxication, stimulates filtration and excretory renal functions. Zosterin delays calcium in the renal tissue in nephrocalcinosis. Therefore, these two factors were incompatible in animals with experimental renal affection. PMID- 11785337 TI - [Effect of various modes of electric stimulation of lower extremity skeletal muscles on indicators of peripheral blood flow]. AB - Various modes of electrostimulation of the musculus gastrocnemius (MG) were examined for effect on doppler parameters of blood flow in the popliteal artery and vein of 15 healthy subjects at the age 30.6 +/- 1.5 years. The strongest effect on the circulation in the popliteal artery was observed at the stimulation with 16-second stimulus alternating with 16-second pause. Such mode led to dilation of the artery diameter by 16.2%, maximal blood flow speed increased by 50.6%, time-averaged circulation was by 60.4% faster. Electrostimulation of the crural muscles also induced dilation of the popliteal vein and accelerated relevant circulation. These changes were also most evident in the stimulation mode 16-second stimulation intermittent with a pause. PMID- 11785336 TI - [Primary and secondary prevention of post-radiation disruption of spermatogenesis in rats under the effect of drinking mineral water]. AB - Drinking sulphate mineral water and that with addition of silicon prevented and restricted postradiation lesions in the spermatogenic epithelium of rat testis. Iodine-containing mineral waters had no protective effect on spermatogenesis. PMID- 11785338 TI - [Effectiveness of complex therapy of eczema patients with the use of various methods of ozone therapy]. PMID- 11785339 TI - [Use of transcranial micropolarization for treating tics in children and adolescents]. PMID- 11785340 TI - [Millimeter wavelength electromagnetic irradiation in the complex treatment of patients with extensive bite wounds]. AB - Patients with extensive bite wounds given conventional treatment and exposed to millimetric electromagnetic waves (MEW) were compared by therapeutic benefit. MEW treatment early after the trauma enhances regeneration in the lesion thus raising therapeutic efficiency of the treatment because the exposure to MEW in hydration phase provides a fast relief of soft tissue edema, lessens intoxication, stimulates adaptation. PMID- 11785342 TI - [Effect of low energy laser energy in woman aged 40-60 with involution dysregulatory disorders]. PMID- 11785341 TI - [Radiation hormesis, radon therapy and radon prevention of disease]. PMID- 11785343 TI - [Physical factors in treating Parkinson disease and Parkinsonism]. PMID- 11785344 TI - [Low-temperature peloids in rehabilitating osteoarthritis patients]. AB - A comparative trial was made of a therapeutic effect of low-temperature (10-24 degrees C) and hot (37 degrees C) applications of mud in osteoarthrosis (OA) patients. Hot applications are highly effective in OA but are contraindicated for patients with synovitis because of the risk of exacerbations. Low-temperature peloids have advantages over standard hot peloids in the treatment of synovitis, in concomitant lymphovenous insufficiency, cardiovascular diseases. PMID- 11785345 TI - [A case of severe HELLP syndrome associated with multiple organ insufficiency]. AB - A case of severe HELLP sd. Was associated with cerebral oedema, anuria, retinal ablation, ascites and hydrothorax. The mother survived after intensive care and therapy, including 10 times haemodialysis. The acute fatty liver of pregnancy (M. Sheehan II) with a much poorer prognosis should be excluded. A diagnostical corticosteroids and prompt delivery is pointed out. PMID- 11785346 TI - [Cervical dystocia and cesarean section]. PMID- 11785347 TI - [New aspects and opportunities in the clinical use of fosamax]. PMID- 11785348 TI - [Microbiology of open surgical wounds after delivery--episiotomy and cesarean section]. AB - The aim of the study is to assess the microbe find in the secretion of the open surgical wounds of the Cesarean Section and the perineal wounds. 81 young mothers have been examined--57 with open perineal wounds on 5th day after the delivery and 24 with open surgical wounds of Cesarean Section on the 7th day after the operation. RESULTS: The west frequent microbe find in the open perineal wounds is Streptococcus group "D" (enterococcus sp.)--53% of the cases and E. coli--26% of the cases. The most frequent microbe find in the open surgical wounds in the Cesarean Section is Enterococcus sp.--42% of the cases and St. aureus--21% of the cases. Considering the effectiveness of Penicillins (Ampicillin, Augmentin, Azlocillin, Karbencillin)--94%-99% against Enterococcus spp. and of Gentamycin against E. coli and St. aureus--90%-95% their application is recommended if is necessary. PMID- 11785349 TI - [VIOXX--a new world without pain]. PMID- 11785350 TI - [Modern therapy with micronized of progesterone--utrogestan for menstrual disturbances]. PMID- 11785351 TI - [Tonocalcin--a powerful and promising drug in the prophylaxis of osteoporosis]. PMID- 11785352 TI - [Treatment with cedax in asymptomatic bacteriuria in the first trimester of pregnancy]. PMID- 11785353 TI - [Preeclampsia--classic and modern concepts and prevention]. PMID- 11785354 TI - [Antenatal anti-Rh(D) antigen prophylaxis]. PMID- 11785355 TI - [ClearPlan--the latest generation test for the rapid diagnosis of ovulation]. PMID- 11785356 TI - [Antenatal anti-Rh(D) antigen prophylaxis of Rh/-/- pregnancy in women on first consultation at the St. Sofia Obstetrics-Gynecology Hospital -- Sofia]. PMID- 11785357 TI - [Indirect (medical) induction of delivery with PgE2-vaginal tablets in high-risk pregnancies]. PMID- 11785358 TI - [Frequency of antiphospholipid antibodies and Leiden mutation of hemostasis Factor V in unexplained recurrent fetal and embryo loss]. AB - Object of the study are women with a history of unexplained recurrent embryo, fetal and early neonatal death, severe preeclampsia, fetal growth retardation, abruptio placentae, puerperal thromboses. Quite often placental insufficiency is linked to abnormal vascular system and hemostatic disturbancies. In about 65% of the women with a complicated and in 18% of the women with a normal pregnancy are observed different genetic anomalies that lead to a hypercoagulative state. A major place is taken by the Leiden mutation of hemostasis factor V, by protein C and protein S deficiency, etc. Another disease that leads to arterial and venous thromboses and is most often linked to recurrent miscarriage is the antiphospholipid syndrome. Many authors confirm the findings of large placental infarctions and thromboses in women who are positive for antophospholipid antibodies. PMID- 11785359 TI - [Rational method for prostaglandin use in cases with postpartal uterine hypotonia]. AB - The authors aim is to find out the most common dosages, roads of administration and the effect of 15-Methyl PgF2a (Prostin 15 M) during the treatment of postpartal uterine hypotony 1 to 3 amp. Of Prostin 15 M-1 ml. (250 mg Carboprost) were used deeply muscular, intracervical or intramyometrial, by 51 patients with postpartal hypotony. The most common risk factors associated with the development of postpartal haemorrhage are PIH, prolonged labour, the general anaesthesis and higli multiparity. The adequate treatment with Prostin 15 M woned reduse the life threatening complication in the Labour room. The most efficient is the intracervical way of administration, a good effect could be achieved even with 1 amp. Prostin 15 M when it is applied after the conventional methods and manipulations. The lacu of effect grow Prostin 15 M (in 5.88% in this study) shows that there is another pathology responsible for postpartal hemorrhage and life threatening hemorrhage and this usually requires Laparotomy. We offer every Obstetric Clinic to have 3 amp. Prostin 15 M available and these would spare a lot of negative feelings or emotions and it wont supply a better obstetric outcomes. PMID- 11785360 TI - [Pregnancy, delivery and perinatal outcome in adolescent pregnancy]. AB - Retrospectively 398 adolescent primiparas have been analyzed in respect of the process of pregnancy, antenatal complications, mode of delivery and perinatal outcome. The researched contingent was divided into 2 age groups--up to 15 years and between 16-18 years. The results obtained were compared to a control group of 398 primiparas at the age of 20-24 years. The results indicate that the process of adolescent pregnancy is related to a substantially higher relative share of some complications like anemia, premature rupture of the membranes and preeclampsia. The frequency of pre-term labor has essentially increased. A basic model of birth-giving is the vaginal delivery, and the duration of delivery of the adolescent does not differ from that of the adult primiparas. There is not a significant difference between the adolescent and the adult pregnant in the placental and in the early puerperal period. An increased frequency of the fetal retardation is missing at the adolescent pregnancy. PMID- 11785361 TI - [Determination of hydrogen peroxide production by vaginal strains of Lactobacillus spp. isolated from healthy women]. AB - Hydrogen peroxide production was determined in 31 strains of Lactobacillus spp., isolated in healthy women. The Lactobacillus spp. Were plated onto Brucella agar containing tetramethyl-benzidine/TMB/and horseradish peroxidase. The plates were incubated under anaerobic conditions at 37 C for 2-3 days, after which the isolates were exposed to ambient air. The horseradish peroxidase in the midium oxidises the TMB in the presence of H202 to from a blue pigment in H2O2-producing colony. 93.3% of the women had H2O2-(+) Lactobacillus spp. and 6.6% had non-H2O2 producing Lactobacillus spp. We postulate that hydrogen peroxide producing Lactobacillus spp. Play the main role for the homeostases of the vaginal ecosystem. This method can easily be applied for the differentiation of H2O2 producing Lactobacillus spp. From non-H2O2 producing Lactobacillus spp. PMID- 11785362 TI - [Our experience in the treatment of polycystic ovary syndrome with Metformin]. AB - Basing on the key role of the hyperinsulinemia in the etiopathogenesis of the Polycystic ovary syndrome, the authors treat the affected women with Metformin. In an 1 year prospective study, including 30 women, they assess the effect of the application of Metformin in relation to some indexes--BMI, WHR, IRI, LH, LH/FSH ratio. After analysing the results, it is reported for a decrease in the absolute values of BMI, WHR and a tendency for redistribution of the adipose tissue from visceral to gynoid type. They report for a statistical reliability in the decrease of LH and LH/FSH ratio. The level of IRI decreases pointedly at every stage of the study. 28 of the patients influence favourably in one or other degree, regarding the menstrual cycles. A good results is also reported in reference to Arterial Hypertension. According to the authors, Mtformin is a good alternative in the treatment of the PCOS. PMID- 11785363 TI - [Perinatal bacterial infections of the newborn infant]. AB - The perinatal bacterial infections are one of the main causes of the neonatal morbidity and mortality. The aim of the present study is to reveal the recent achievements in the prenatal identifying and prevention of the neonatal infections and to discuss the pathogenic mechanisms and risk factors for their development. The contemporary laboratory tests for early diagnosis of neonatal sepsis and its clinical manifestations and the therapeutic strategies in the different forms of sepsis and new prophylactic methods are reviewed. PMID- 11785364 TI - [Pregnancy with Rh-isoimmunization. Results of a retrospective analysis in the maternity hospital "Maichin Dom"]. AB - The aim of the study is to analyze the outcome of pregnancies complicated by Rh isoimmunization for the period 1996-2001 and to outline the aspects of optimization of the obstetrical conduct. MATERIAL AND METHODS: The current study includes 39 pregnant women with Rh-isoimmunisation to whom amniocentesis and cordocentesis was performed. All cases were analyzed using medical history, serology (indirect Coombs, PAP test), ultrasound examination, amniocentesis, cordocentesis, NST. RESULTS: From 39 pregnancies, complicated by severe Rh isoimmunization 36 resulted in a live delivery, 2 resulted in intrauterine death of the fetus and 1 in early neonatal death. The titre of the antibodies is of prognostical value only in the first isoimmunised pregnancy. In this case there is a reliable correlation between the condition of the newborn and the zone from the Liley curve, antenatally found. With history of former immune pregnancies with unfavourable perinatal outcome most precise information about the condition of the foetus gives the cordocentesis. CONCLUSION: In all of the discussed cases the Rh-isoimmunization is a result of no andi-D immunoglobulin profilaxis post partum or following abortion. That is why the efforts should be directed towards conduction of proper profilaxis to all Rh-negative pregnant women. PMID- 11785365 TI - [The role of antisperm antibodies in the induction of immunologically-mediated human infertility]. AB - Among others, immonulogical factors can be the reason for human infertility. Our critical review of English-Language literature published between 1979 and May 2001, as well as the analyzed literature data for the Bulgarian population, showed sufficient evidence that antisperm antibodies impair fertility in couple with unexplained infertility by different pathogenetic mechanisms. PMID- 11785366 TI - [Pregnancy complicated by ovarian cysts]. AB - OBJECTIVE: To study outcome of pregnancy complicated by ovarian cysts, clinical behavior of functional cysts, efficiency of conservative and operative management during pregnancy and labor. MATERIAL AND METHODS: Twenty-three women with diagnosed ovarian cysts less than 5-6 cm in the early first trimester of pregnancy were followed by a two year period (1999-2000). Relationship between the sonographically change of cysts and pregnancy outcome was determinate. RESULTS: In a group of 23 women with ovarian cysts, 16 were successful pregnancies as followed: 12 ended in normal vaginal deliveries and 4 delivered by cesarean (1 obstetric indicated; 2 persisted cysts--serous and mucinous custadenoma; 1 after operated in 18 gest. Week border line cystadenoma). Of the last 7 pregnancies were operated and 3 electively terminated (1 blighted ovum and 2 missed abortions). CONCLUSION: Ovarian cyst in first trimester of pregnancy with maximum size 5-6 cm usually were reached until the 7-8 week, maybe followed by functional corpus luteal cysts, involuated until 14 gest. Week, rarely persisting and isn't expected to grow after 14 gest. Week or to cause complication in pregnancy and labor. PMID- 11785367 TI - [Osteogenesis imperfecta - diagnostic challenges]. AB - Osteogenesis imperfecta (OI) is one of the commonest skeletal disorders with an incidence about one in 10,000. It is characterized by clinical and genetic heterogeneity. Congenital lethal OI (OI type II) is the most severe from with a possibility of the early prenatal sonographic diagnosis. The authors present two clinical cases of antenatal diagnosis of OI in 26 and 24 weeks of gestation. The pregnancies were terminated. The accurate specific diagnosis was based on the clinical examination and radiographic features. In case N 2 additional findings were ascites and hydrothorax, that may occasionally be found in literature. The accurate prenatal sonographic diagnosis of lethal skeletal dysplasias and particularly of OI is possible and based on the specific sonographic findings during the second trimester of pregnancy. Ultrasound screening of all pregnant women in early second trimester is an efficient method for detection of many fetal malformations. It requires a participation of the both clinician sonographer and geneticist in a team in order to achieve a specific genetic diagnosis. PMID- 11785368 TI - [A case of multiple pregnancy (twins) in each cavity of a double uterus and a vaginal septum]. AB - A case of a multiple pregnancy in each of the horns of a double uterus with a double cervix and a vaginal septum is discussed. The uterine malformation was known prior to pregnancy. In 34 g. w. a Ceasarean section was performed because of premature rupture of membranes. Two premature infants were born with no evidence of present pathology. PMID- 11785369 TI - [Influence of maternal position during delivery of fetal oxygen saturation]. AB - The aim of the study is to investigate the alterations in fetal oxygen saturation during right lateral, supine and left lateral maternal position. Thirty six women at term are included--during the first stage of normally progressing labour. Simultaneous monitoring is carried out of fetal heart rate, uterine contractions, fetal oxygen saturation and maternal arterial blood pressure for a certain period of time in different maternal positions. It was established, that fetal oxygen saturation values are lowest in the supine position, still remaining in physiological ranges--47.1 +/- 10.2. If supine syndrome develops, fetal oxygen saturation values decrease significantly: 23%, 25%. PMID- 11785370 TI - [Insufficient validity of a rapid blood test for diagnosis of Helicobacter pylori infection]. AB - BACKGROUND AND AIM: Rapid blood tests for diagnosis of Helicobacter (H.) pylori infection enable to detect antibodies against H. pylori instantly without laboratory equipment. Primary aim: to validate the Helisal Rapid Whole Blood Test (HRBT) with endoscopic bioptic methods as reference. Secondary aim: to compare the HRBT with ELISA IgG serology. PATIENTS AND METHODS: The HRBT was performed in 145 consecutive dyspeptic patients (median age 59 years) before undergoing esophagogastroduodenoscopy including biopsies from gastric antrum and corpus. A positive H. pylori status was defined by a positive culture or the combination of a positive rapid urease test and a positive histology. Serum for ELISA IgG testing was available from 92 patients. RESULTS: The H. pylori status was positive in 66% of the patients. The sensitivity of the HRBT resulted at 80%, the specificity at 82%. The sensitivity of the HRBT for a positive ELISA test amounted to 87%, the specificity to 96%. CONCLUSIONS: The diagnostic validity of the HRBT is insufficient for clinical application. False test results add up by the general discrepancy between serological and bioptic methods and by diminished sensitivity compared to ELISA serology. PMID- 11785371 TI - [Clinical characteristics of patients with AV-nodal reentrant tachycardia (AVNRT): modification by high frequency catheter ablation. Study of 748 patients after high frequency catheter ablation]. AB - AIM: The aim of the study was to analyze the medical history of patients with AV nodal reentry tachycardia (AVNRT). PATIENTS AND METHODS: Between 1990 and 1999 radiofrequency catheter ablation was performed in 1,024 patients suffering from AVNRT. Data of the previous history were comprehended by questionnaire. RESULTS: 748 (73%) patients replied to the questionnaire. The interval between the first appearance of the symptoms and the catheter ablation was 4.1 +/- 1.5 years. The mean age of the patients was 55.4 years (female) and 58.7 years (male). Merely 6% of all patients had a structural heart disease. The mean duration of case history was 16.8 years. In comparison to the male patients, the assignment for female patients to catheter ablation was after a significant 7 years longer lasting anamnesis. The distribution of age showed that the first tachycardia appeared in 16% of the female patients older than 50 years of age and only in 17% younger than 20 years of age; the corresponding percentages for men were 31% and 18%. With reference to the duration of the longest tachycardia episodes and arrhythmia related presyncopes and syncopes, women showed a more defined symptomatic. On 20% of the patients a radiofrequency catheter ablation ensued without previous antiarrhythmic treatment; 80% of the patients were treated with 2.8 different antiarrhythmic medications. Medical consultations regarding AVNRT were named as follows (mean/range): family doctor 6.1/1-250, emergency physicians 1.1/0-15, hospital 1.0/0-20. The indication for catheter ablation was set by the family doctor in 13% and by the cardiologist in 77%. Patients got their information about catheter ablation in 2.9% from acquainted persons or news services. CONCLUSION: There is no "typical" anamnesis of AVNRT patients. There is an amazingly high rate of patients with an AVNRT begin in elder stage of age and the fact of therapy delay of 7 years in behalf of women. PMID- 11785372 TI - [Synergistic effects of combined therapy of inhalational glucocorticosteroids with long-acting beta 2-receptor agonists in treatment of bronchial asthma]. AB - BACKGROUND: Due to the potent anti-inflammatory strength, glucocorticosteroids are the basis of long-term (controller) therapy in asthma. They inhibit transcription of pro-inflammatory cytokines and block humoral as well as cellular derived inflammation in the bronchi. beta 2 sympathomimetics are well known to cause dilatation of the bronchi but also to modulate certain anti-inflammatory responses. SYNERGISM: Just recently it could be demonstrated that beta 2 agonists may also be able to activate glucocorticosteroid receptors, independently of existing glucocorticosteroids. Thus, beta 2 agonists lead to augmentation of glucocorticosteroid receptor concentration, and consequently cause better efficacy of glucocorticosteroids within the cell. Vice versa glucocorticosteroids enhance the transcription rate of beta 2 receptors, causing higher beta 2 receptor number, and thus may contribute to better beta 2 agonist efficacy. These synergies of beta 2 agonists and glucocorticosteroids on molecular level explain additive efficiency in the therapy of asthma--particularly through improving lung function--when using both substances in combination. PMID- 11785373 TI - [Pleural mesothelioma. I: History, epidemiology, clinical aspects (symptoms, diagnosis)]. AB - EPIDEMIOLOGY: Although production and processing of asbestos have been prohibited for years, the incidence of mesothelioma of the pleura will rise in Western Europe. The incidence of mesothelioma will peak between the years 2010 and 2020. It will cause an estimated 250,000 deaths within the next 35 years. PATHOGENESIS: The fact that exposure to asbestos fibers may result in mesothelioma was first described in 1960. The risk of developing mesothelioma depends mainly on the type of asbestos fibers and the way asbestos is manufactured. Environmental eronite fibers in Central Turkey are the cause of endemic mesothelioma. The pathogenetic role of infection with simian virus 40 is still not determined. Thoracic radiation is of minor importance in the etiology of pleural mesothelioma. DIAGNOSIS: Between first symptoms of disease and diagnosis of mesothelioma often more than 6 months pass as clinical symptoms are rarely typical. Detection of early stages by invasive procedures and imaging is often very difficult. Histopathological distinction between adenocarcinoma and mesothelioma requires experienced pathologists. This implies that management of mesothelioma should only be performed in multidisciplinary cooperation in specialized centers. PMID- 11785374 TI - [Aortic stenosis with low transvalvular pressure gradients and impaired left ventricular function. Dobutamine stress echocardiography helps in therapy planning]. AB - BACKGROUND: Aortic valve replacement is recommended in case of symptomatic severe aortic stenosis. This decision is difficult for patients with low-gradient aortic stenosis and severely impaired left ventricular function because of high perioperative mortality in this group. Although aortic valve replacement is usually justified if severe aortic stenosis is proved, patients with primary myocardial dysfunction and subsequent reduced aortic valve opening do not benefit from aortic valve replacement. Distinguishing these two groups of patients is necessary but not possible with echocardiography at rest. Positive inotropic stimulation with dobutamine stress echocardiography enables a more reliable graduation of aortic stenosis under these circumstances. CASE REPORT: We report on a symptomatic 58-year-old man with aortic stenosis and severely impaired left ventricular function. Using echocardiography at rest, there was a severely reduced aortic valve area of 0.6 cm2 and a mean pressure gradient of 24 mm Hg. Determined by cardiac catheterization, the peak-to-peak gradient was 20 mm Hg and the aortic valve area calculated by the Gorlin formula was 0.6 cm2. After positive inotropic stimulation using dobutamine stress echocardiography, the aortic valve area increased to 1.5 cm2 indicating an only moderate aortic stenosis. Thus aortic valve replacement was not performed and myocardial failure was medically treated. After 1.5 years of follow-up, the patient is in good condition and without complaints. PMID- 11785375 TI - [75-year-old patient with persistent abdominal complaints and vomiting during a cruise]. AB - BACKGROUND: In elderly patients with gallstone disease, a gallstone ileus must be considered for unexplained abdominal pain. This is demonstrated in the following case report. CASE REPORT: A 75-year-old female patient presented with a 72-hour history of abdominal pain, nausea and vomiting. The patient's abdomen was mildly distended, although soft and nontender with bowel sounds present. Plain radiographs and ultrasound investigation of the abdomen were compatible with small bowel obstruction. To clarify the etiology, an abdominal computed tomography scan was obtained. These examinations disclosed air in the biliary tree, dilated small bowel and an impacted intraluminal abnormality in the terminal ileum compatible with a gallstone. Operative intervention confirmed the presence of a 3 cm obstructing calculus in the terminal ileum that was removed by an enterolithotomy. A two-step cholecystectomy and closure of the cholecystoduodenal fistula were performed 8 weeks later. The patient's recovery was uneventful. CONCLUSIONS: Although rare in a general population, gallstone ileus accounts for 25% of nonstrangulated small bowel obstructions in patients over the age of 65. The radiographic picture and ultrasound of small bowel obstruction and the presence of air in the biliary tree are suggestive for the diagnosis of a gallstone ileus. In our patient, the computed tomography and ultrasound findings confirmed the diagnosis and led to a prompt and directed surgical intervention. In patients with comorbid factors a two-step approach with enterolithotomy in a first and cholecystectomy in a second operation should be the therapeutic strategy of choice. PMID- 11785376 TI - [Epithelioid hemangioendothelioma of the spine]. AB - BACKGROUND: Epithelioid hemangioendotheliomas are rare vascular tumors, mostly originating from soft tissue, lungs or liver. CASE REPORT: A 58-year-old woman was admitted to hospital because of upper congestion, Horner's syndrome and segmental sensory disturbance. MRI of the spine showed a spinal mass, reaching from the seventh cervical vertebra to the fourth chest vertebra. Because of worsening of upper congestion and progressive neurological impairment, the patient had to be operated twice. Unfortunately a surgical excision of the infiltrating tumor in sano was not possible and the patient died 4 weeks after the second operation. Histologic examination revealed the diagnosis of infiltrating epithelioid hemangioendothelioma, originating from the first chest vertebra. CONCLUSION: Prognosis of epithelioid hemangioendothelioma is mainly determinated by its location. In advanced stages of disease or lack of surgical cure epithelioid hemangioendotheliomas may be fatal. Therefore epithelioid hemangioendotheliomas should be considered early in the differential diagnosis of patients with uncertain bone lesions. PMID- 11785377 TI - [Multiple lipomas in MEN 1--a rare finding in rare disease picture]. PMID- 11785378 TI - [Medical care is a science, or it cannot exist]. PMID- 11785379 TI - [External quality assurance in Germany. The current status]. AB - BACKGROUND: The so-called "external quality assurance" allows the comparison of hospitals using selected quality indicators for process and outcome of care. The methods were developed in early projects of perinatologists and surgeons in the mid 70s. The comparative statistics inform hospitals about their strengths and deficiencies compared to other hospitals. STATE OF THE ART: Since 2001 the Federal Committee on Quality Assurance (Bundeskuratorium Qualitatssicherung) requests the realization of external quality assurance measures for 27 diseases and procedures in all German hospitals based on the 5th Social Law. If hospitals refuse participation or participate incompletely, they have to expect financial sanctions. The comparative statistics enable first assessments of the quality of hospital care. However, the methods have to be improved if they will be used to demonstrate quality of hospital care to people outside the hospitals. PMID- 11785380 TI - [Use of molecular biological method (MAPREC-test) for evaluating residual neurovirulence and genetic stability of oral poliovirus vaccine type 3]. AB - MAPREC test (mutant analysis by polymerase chain reaction and restriction enzyme cleavage), evaluating the content of neurovirulent mutants with nucleotide substitution of U for C in position 472 in the 5'-nontranslated RNA region, in a virus population was used for a retrospective analysis of 3 specimens of inoculated viruses and 55 lots of type 3 oral poliovirus vaccine (OPV) prepared at M. P. Chumakov Institute of Poliomyelitis, Russian Academy of Medical Sciences, during recent 6 years. The mean content of neurovirulent mutants in inoculated viruses was 0.26 +/- 0.06%, in monovaccines 0.34 +/- 0.04% (the maximum allowable content is 1%). The method is well reproducible and detects about 0.1% mutants in the population. MAPREC test can be used instead of currently used residual virulence control on monkeys, as it detects viral preparations which were not tested on monkeys and does not reject high-quality vaccines. The protocol of using this method in combination with other methods for neurovirulence and genetic stability control of type 3 OPV is discussed. PMID- 11785381 TI - [Expression of endogenous retroviruses of the HERV-K/HTDV family in patient with germinogenic tongue tumors]. AB - Transcription of HERV-K/HTDV proviruses in various morphological forms of GCTs and in normal testicular parenchyma and placenta was studied by RT-PCR with specific primers discriminating type 1 proviruses from type 2 ones. The results indicate that transcription of type 2 HERV-K/HTDV proviruses takes place and mRNA of protein cORF, coded for only by type 2 proviruses, is synthesized in all malignant germinogenic tumors. In normal testicular tissue and placenta type 1 HERV-K/HTDV proviruses are expressed. No expression of HERV-K/HTDV proviruses was detected in nongerminogenic testicular tumors. Since cORF protein possesses transforming activity, its possible role in the pathogenesis of GCTs is discussed. Generation of humoral immune response to structural HERV-K/HTDV proteins in various morphological forms of GCTs confirmed the possibility of using antibodies to structural HERV-K/HTDV proteins as additional markers of GCTs. PMID- 11785382 TI - [Production and study of hybridomas, producing monoclonal antibodies to the structural glycoprotein of Marburg virus]. AB - Hybridomas producing monoclonal antibodies (MAb) to Marburg virus glycoprotein were prepared by splicing of mouse myeloma cells (NSO and X.63-Ag6.653 strains) and splenocytes of immunized BALB/c mice. Cultural and MAb-producing properties of hybridomas were studied. The production of MAb during serial passages 15-30 was confirmed. MAb titers in culture fluids were 1:4096-1:8152, in immune ascitic fluids of BALB/c mice 1:409,600-1:638,400. The possibility of using MAbs as a component of ELISA test system was demonstrated. The sensitivity of ELISA-MAb method for Marburg virus was 1 x 10(3) PFU/mu. PMID- 11785383 TI - [Prophylactic efficacy of aerosol preparations based on Abies siberica polyprenols in experimental influenza infection]. AB - Preliminary investigations showed high preventive activity of two of three aerosol preparations of Abies sibirica polyprenols with nonionic surface active substances towards influenza infection. At least 2 aerosol administrations are needed to attain a high protective effect, the second dose depending on the first. Relationship between animal reaction to influenza virus infection changed in a nonmonotonous mode, depending on the drug dose injected during the first treatment: as the dose increased, the death rate first decreased and reached the minimum and then increased again. Such a reaction to aerosol treatment can be explained by the hypothesis of hyperstimulation followed by exhaustion of the host defense systems after high doses of the preparation. PMID- 11785384 TI - [Mechanisms of action of aerosol preparations based on Abies siberica polyprenols in experimental influenza infection]. AB - Humoral and cellular mechanisms of Abies sibirica polyprenol effects on nonspecific resistance of mice to influenza A/Aichi/2/68 virus were investigated. Two aerosol doses of polyprenols had a high protective effect in mice challenged with influenza virus. Aerosol polyprenol preparations in the studied doses induced no interferon or tumor necrosis factor production in the lungs. Lung macrophage counts and capacity to produce superoxide anion radicals increased in survivors after influenza in comparison with intact animals. Double aerosol administration of polyprenols prior to influenza infection promoted an increase in the thymus weight, bronchoalveolar tract cell counts (predominantly at the expense of lymphocytes), and of superoxide-producing potential of macrophages, which, in turn, can contribute to improvement of the defense potential of the organism towards influenza virus. PMID- 11785385 TI - [Monoclonal antibody study of antigens E and NS1 of Western Siberian tick borne encephalitis virus strains]. AB - Antigenic structure of tick-borne encephalitis virus proteins was studied by ELISA with monoclonal antibodies (MAb) to E and NS1 glycoproteins of strain Sofyin. Envelope proteins appeared to be conservative which corresponded to previously determined nucleotide sequences of E gene fragments and deduced primary structures of the corresponding E protein. Five of six studied MAb to NS1 nonstructural glycoprotein of strain Sofyin reacted with this protein of all studied strains. The only exception was MAb 17C3 which discriminates West Siberian strains from Far Eastern strain Sofyin. PMID- 11785386 TI - [Production of cytokines from blood donor leukocytes]. AB - Cytokine production by donor blood leukocytes was investigated in vitro. LPS stimulation led to the production of IL-1 beta, IL-6, and TNF-alpha, if their spontaneous production was below the threshold sensitivity of the test method, and to a statistically negligible increase of production if spontaneous production was pronounced. The concentrations of cytokines produced depended on the nature of inductors and their doses. The inductor modulating effect can be used for stimulation and inhibition of cytokine production. PMID- 11785387 TI - [Chronically HIV-1 infected human monocyte culture U937 as a model for assessing the efficacy of anti-HIV agents]. AB - Cell culture U937 chronically infected with HIV-1 is suggested as a model for adequate evaluation of antiviral activity of HIV inhibitors. Azidothimidine (AZT) notable decreased HIV-1 reproduction in chronically infected U937 cells to passages 15-18. Glycirrhizic acid (GA) effectively inhibited the virus production during the first four passages, while in subsequent passages (up to passage 20) decreased the virus production by only 60% in comparison with the control. If a combination of AZT and GA (1:1000) was used, p24 was not detected in the culture fluid by passage 20. Culturing of U937 cells with AZT led to a 10-fold decrease in the amount of DNA 2-LTR in comparison with the total content of proviral DNA, the content of HIV-1 DNA 1-LTR remaining virtually unchanged. Culturing of U937 with a combination of AZT and GA resulted in a notable decrease in the content of proviral DNA 2-LTR after passage 3, while after passage 9 this form of HIV-1 DNA was not detected at all. PMID- 11785388 TI - [Basic results of studies on the problem of AIDS in 2000]. PMID- 11785389 TI - [Dynamics of expression of Marburg and Ebola virus antigens in infected Vero cells ]. AB - Time course of Marburg and Ebola virus antigens expression in Vero cells was studied by indirect immunofluorescence test. The maximum accumulation of virus specific antigens in Vero cells infected with a high dose was observed after 48 54 h of incubation. It is essential for laboratory diagnosis that virus specific antigens can present as incorporations of different shape and size, starting from small hardly discernible granules (immediately after the virus adsorption) to large lumps, cords, accumulations, and diffuse fluorescence. PMID- 11785390 TI - [Evolution of influenza B viruses at the end of the 20th century]. AB - Influenza B viruses (48 strains) isolated in Russia in 1992-2000 have been investigated. The majority (29 strains) were isolated in 1994-1995. The strains were isolated in embryonated eggs and MDCK cells. Study of their antigenic properties showed that all of them belonged to an evolutionary group B/Jamagata/16/88-like viruses. Antigenic drift in the hemagglutinin (HA) of epidemic strains isolated in Russia was the same as in reference strains of this evolutionary group. HA proteins of isolated and reference strains differed by 8 12 amino acid sequence positions. Paired sera of patients with influenza-like diseases collected during this decade were tested. Seroconversions to B/Jamagata/16/88-like strains were discovered for during the entire period of observation, while seroconversions to reference strains of the B/Victoria/2/87 group only in 1999-2000 season, which can be regarded as activation of these viruses in Russia. PMID- 11785391 TI - [Application of clexane in reconstructive surgery of the aorta arch vessels for the arterial thrombosis prophylaxis]. AB - Results of treatment of 114 patients for ten-year period, operated on for diseases of extracranial vessels, were adduced. Up to 1998 after performance of reconstructive operation as anticoagulant heparin was used in 80 patients and in last time--low-molecular heparin clexane in 34. After operation all patients survived. An ischemic insult occurred in 2-3 days after the operation in 2(2.5%) patients, while application of heparin, in 5--positive changes of the disease course were absent, in 19(23.75%)--postoperative hemorrhagic complications occurred. When clexane was administered in 2(5.9%) patients the cerebral hemodynamics improvement was not noted, complications in the early and late postoperative periods were absent. In term of observation up to 5 years good results was noted in 21(62.3%) patient, fair--in 9 (27.2%). In late postoperative period the brain hemodynamics improvement was not noted in 2 (5.9%) patients. Application of clexane for the arterial thrombosis prophylaxis is clinically substantiated and permits to reduce significantly the risk of the complications occurrence, which are observed with usage of heparin. PMID- 11785392 TI - [Experience of application of lymphotropic methods in the treatment of lower extremity veins]. AB - Experience of treatment of 368 patients with disease of veins of lower extremities was summarized. In patients with an acute thrombophlebitis and chronic venous insufficiency of lower extremities significant disorders of microhemo- and lymphatic circulation, manifesting as venous or lymphatic stasis, were noted. Conduction of lymphotropic therapy have promoted microcirculation improvement, elimination of interstitial oedema and signs of inflammation, permitting to shorten the stationary treatment period. PMID- 11785393 TI - [Clinical criteria in the diagnosis of mild and occult forms of coagulopathy and thrombocytopathy]. AB - Clinical criteria of diagnosis of mild and occult forms of coagulopathy and thrombocytopathy were discerned. It was established, that in such diseases the mixed type of hemorrhagic diathesis predominates. There were analyzed the most characteristic hemorrhagic signs and frequency of their occurrence in these forms of hemostasis pathology. PMID- 11785394 TI - [Application of adjustable gastric bandage in surgical treatment of morbid obesity]. AB - Experience of surgical treatment of 8 patients with morbid obesity, using regulated cuff Lap Band, was adduced. Body mass of patients have constituted from 105 to 185, (14.5 +/- 2.5) kg at average, body mass index--from 38 to 60 kg/m2. In all patients good result of treatment was noted in term from 6 to 28 months. Immediate results of the method usage gives evidence of its efficacy. PMID- 11785395 TI - [Choice of methods of surgical treatment and postoperative period management in patients with duodenal ulcer complicated by hemorrhage during continuous influence of small radiation dosage]. AB - Results of surgical treatment of duodenal ulcer, complicated by hemorrhage, in patients, who were exposed to the small doses of radiation influence, are unsatisfactory. General, local immunity were studied up, pH-metry of gastroduodenal zone was conducted, activity of Helicobacter pylori (HP) urease was determined in patients with duodenal ulcer, complicated by hemorrhage, who have been exposed for a long time to the small doses of radiation influence and who were not. In patients, who have been exposed to radiation influence, reduction of secretory immunoglobulin A (sIgA) in duodenal mucus was revealed. Conduction of the local immunity changes correction, performing organpreserving surgical intervention and using immunocorrecting therapy after the operation, are recommended for improvement of the surgical treatment results. PMID- 11785396 TI - [Endoscopic choledochoduodenostomy]. AB - Method of endoscopic choledochoduodenostomy was elaborated and introduced in clinical practice. Results of formation of endoscopic biliodigestive anastomosis in 12 patients for 1990-2000 yrs period were analyzed. In 7 (5.8%) patients complications occurred, 1 (0.8%) patient died. PMID- 11785397 TI - [Fundamentals of complex treatment of acute destructive pancreatitis]. AB - Results of treatment of 240 patients with an acute pancreatitis were analyzed. There were assigned two groups taking into account stage of severity of pancreonecrosis and stage of polyorganic insufficiency. In 147 patients with mild stage and moderate stage conservative treatment was undertaken, in 93 patients with severe course different operative interventions were performed in urgent and emergent order and in period of postnecrotic complications occurrence. Application of such an approach have permitted to lower the postoperative complications frequency in 1.9 the value. Mortality had constituted 22.6%. PMID- 11785398 TI - [Results of diagnostic laparoscopy in patients with acute pancreatitis]. AB - Diagnostic laparoscopic intervention was performed in 339 patients with preliminary diagnosis of an acute pancreatitis (AP). In 164 (48.4%) patients other acute surgical disease was diagnosed and in 175 (51.6%)--an AP. After performance of laparoscopy 11 patients were operated on, in 164 (93.7%)--curative laparoscopic intervention was done. Diagnosis of AP was established in 15 (8.6%) patients during conduction of laparotomy, in 1 (0.6%)--during pathomorphologic investigation. Complications occurred in 4 (2.3%) patients. PMID- 11785399 TI - [Surgical treatment of acute cholecystitis in elderly and senile patients]. AB - There were analyzed the results of treatment of 69 elderly and senile patients, operated on for an acute calculous cholecystitis, in 19 of whom cholecystectomy, using miniapproach was performed. The performance of an assisting manipulating channel, application of oblique-changing puncture of gall bladder and of special instruments were proposed to improve technical condition of cholecystectomy performance while usage of miniapproach, its rational exploitation and reduction of intra- and postoperative complications occurrence. PMID- 11785400 TI - [Complications of acute lesions of the digestive tract as a direct cause of mortality in patients with advanced forms of neoplasms in palliative and symptomatic treatment]. AB - There were analyzed an autopsy protocols of 117 patients with oncological disease, in whom during performance of pathomorphological investigation an acute erosive-ulcerative affection (AEUA) of digestive channel (DCH) was revealed, of them in 69 patients palliative and/or symptomatic treatment for extended forms of cancer was conducted. Structure of principal complications as well as their significance in pathogenesis, localization of affection, influence of different methods of palliative treatment on AEUA DCH occurrence. The data obtained must be taken in account during planning of palliative therapy in such patients. PMID- 11785401 TI - [Specifics of preparation of patients with polycystic renal disease for forthcoming kidney transplantation]. AB - Results of treatment of 28 patients with polycystic kidney were presented. In 12 (42.9%) patients with terminal stage of chronic renal insufficiency transplantation of kidney (TK) was performed without preliminary nephrectomy or nephrectomy was done simultaneously with TK. In 16(57.1%) patients nephrectomy was performed in stage of preparation to allotransplantation. Were established advantages of preliminary performance of nephrectomy in patients with polycystosis on stage of preparation to TK: in one-year follow-up the settle down of renal allotransplant was noted in all patients. PMID- 11785402 TI - [Reoperations in thyroid gland cancer]. AB - Results of reoperation for the thyroid gland cancer (THGC) were analyzed in 189 patients for 1981-2001 yrs period. Majority of patients were primarily operated in other hospitals of Ukraine. Thorough characteristic of the cancer forms, terms of reoperation performance, results of histological investigation of the tumor are adduced. Large frequency (41.2%) of the operation performance for THGC recurrences in term up to one years after performance of primary intervention trusts the necessity of operative intervention performance on thyroid gland (THG) in specialized centre by experienced surgeons. Absence of malignant growth in the THG stump while performance of definitive thyroidectomy in 60% of observations is not the cause to reject of doing it because the conduction of radioiodine therapy is possible after complete excision of the THG tissue. Examination and ultrasonographic investigation of the THG region and of cervical lymphatic nodes after performance of operation for THGC is recommended to conduct no less than once in 6 months. PMID- 11785403 TI - [Mediastinal tumors and tumor-like formations in children]. AB - Twenty-five years experience of diagnosis and results of treatment of 143 childs aged from 10 days to 15 years with sizable mediastinal formations was summarized. Benign tumor was revealed in 50 (34.96%) childs, malignant one--in 93 (65.04%). Groups of most important symptoms were suggested: generally somatic, compressive, neurological. Principal method of diagnosis of mediastinal tumor in children--the survey roentgenography of thoracic organs in two projection. Immediate and late follow-up results of operative intervention were estimated, diagnostic mistakes were analyzed. PMID- 11785404 TI - [Treatment of newborn children with gastroschisis]. AB - In 1996-2000 yrs 20 children with gastroschisis were operated, of whom 9 died. Tactics of application of general anesthesy in conjunction with spinal and caudal anesthesy, permitting to lower mortality of newborn children with gastroschisis, was enlightened. PMID- 11785405 TI - [Surgical infection in reconstructive vascular surgery]. AB - There were analyzed the results of treatment of 1514 patients, to whom different reconstructive operations on vessels were performed. In 88 (5.8%) of them infectious-inflammatory complications occurred. Three groups of complications were assigned: superficial (in 43.2% observations), deep (in 44.3%) and common infectious (in 12.5%). To all the patients treatment was conducted, in 93.2% of observations positive result was noted, mortality had constituted 2.3%, amputation of lower extremity was performed in 4.5% of patients. There were assigned predisposing factors for the infectious complications occurrence. Complex of curative and prophylactic measures for application in reconstructive vascular surgery was elaborated. PMID- 11785406 TI - [Surgical treatment of cryptorchidism in children with deep inguinal ring translocation]. AB - Results of surgical treatment of 83 boys with cryptorchidism were analyzed. Three stage approach of simultaneous descendence of testicle was proposed: performance of m. cremaster plasty, using muscular flap, excised from m. obliquus internus abdominis, transposition of anulus inguinalis profundus in medial direction and to tuberculum pubicum, securing necessary elongation of elements of funiculus spermaticus for the testicle descendence in 98% of observations. PMID- 11785407 TI - [Surgical treatment of spinal arteriovenous fistula]. AB - 38 patients with spinal arteriovenous fistula (AVF) were treated. In 23 of them dural AVF (DAVF) was diagnosed, in 15--intradural perimedullar fistula (IPAVF). Transvasal embolization was conducted in 4 patients as an independent intervention, and in 7 patients--as a first stage before open microsurgical intervention. Open microsurgical intervention was conducted in 34 patients. The indications to microsurgical and transvasal intervention or their combination are substantiated. The interaction of treatment results and arteriovenous malformation was studied. PMID- 11785408 TI - [Pancreatic pseudocyst as a complication of acute pancreatitis]. AB - New hypothesis of the pancreatic pseudocyst (PPC) pathogenesis, intending detachment of nourishing "segment" of the organ as the source of the cystic cavity filling, is presented. An experiment on forming of internal anastomosis with cystic cavity and pancreatic duct was done. The model of suppurated PPC was elaborated, to treatment of which the ointments levosin and ophlotrimol, possessing noncorrect necrolytic activity, were applied. In experimental investigations the perspective of conduction of the PPC (already formated and "unripe" as well) curative decompression was shown and efficacy of the ointment compositions for the treatment of suppurated PPC too. PMID- 11785409 TI - [Current problems of surgical treatment of thymoma in children]. PMID- 11785410 TI - [Experience in surgical treatment of pulmonary and mediastinal tumors after intraoperative histology using video-thoracoscopy]. PMID- 11785411 TI - [Observation of coexistent Mellory-Weiss syndrome and esophageal wall perforation]. PMID- 11785412 TI - [Strangulation of the left hepatic lobe in hernial sac]. PMID- 11785413 TI - [Observation of pancreatic incidentaloma]. PMID- 11785414 TI - [Methods of myocardium defense in radical correction of Ebstein anomaly]. AB - Experience of myocardium defence while correcting Ebstein anomaly in 75 patients was analyzed. In 25 patients antegrade pharmacorefrigerating crystalloid cardioplegia based on potassium chloride was applied, in 10--method of Kirsch using miganesiun-aspartate-procaine solution. In 40 patients antegrade pumping of normothermic potassium chloride solution with subsequent antegrade infusion of cooled magnesium-aspartate-procaine solution applied for primary heart arrest. Application of combined defence of myocardium using normothermal crystalloid cardioplegia and refrigerating, of antegrade infusion of magnesium-asparate procaine cardioplegic solution has advantages in comparison with another methods of myocardium defence, reduces the threat of an acute cardiac insufficiency occurrence in early postoperative period. PMID- 11785415 TI - [Isolation and characterization of Cytophaga lytica lipopolysaccharide]. AB - Lipopolysaccharide (LPS) and its structural components: lipid A, O-specific polysaccharide (O-PS) and oligosaccharide core (OG-core) have been isolated from Cytophaga lytica. 3-Oxytetradecanoic (40.8%) and dodecanoic (28.7%) are the predominant fatty acids of lipid A; pentadecanoic (6.8%), 3-oxyhexadecanoic (6.5%) as well as hexadecanoic (5.4%) acids have been found as well. The content of the rest of fatty acids is inconsiderable (2.3 to 0.5%). OG-core contained monosaccharides both typical of the most Gram-negative bacteria (glucose, mannose, galactose, rhamnose, glucosamine) and rarely occurring one-arabinose. O PS is represented by glucose, mannose, rhamnose, glucosamine, galactosamine as well as unidentified hexosamine. PMID- 11785416 TI - [ATPase activity of Neisseria gonorrhoeae and Staphylococcus aureus strains]. AB - It has been established that membrane vesicles of gonococci possess ATPase activity within 0.05-0.14 mmol of ATP during 60 min per 1 mg of protein and for staphylococcus--within 0.07-0.19 mmol of ATP for 60 min per 1 mg of protein. The identity in all the kinetic parameters is observed for all the studied gonococcus strains: Na+ and Ca2+ ions inhibit ATPase activity within 12-19%; Mg2+ ions increase the ATPase activity 2-2.5 times. Dicyclohexylcarboimide, a specific ATPase inhibitor, suppresses ATPase activity by 50-70%. ATPase activity in the strains of bacteria containing antibiotic-resistant plasmids is established to increase 1.2-2.8 times for gonococcus and 1.2-2.7 for staphylococcus as compared to sensitive ones. PMID- 11785417 TI - [Auxotrophy and utilization of oxidized and reduced mineral sulfur forms by Brevundimonas diminuta strains]. AB - Connection between auxotrophy of Brevundimonas diminuta strains for sulphur containing amino acids and presence of oxidized or reduced sulphur forms in the medium has been shown. When grown in synthetic medium supplied with sulphate or sulphite B. diminuta strains required cystine, biotin, pantothenate and vitamin B12 for growth and utilized very limited spectrum--from 8 to 12--carbon sources. In the presence of 5 g/l of thiosulphate in the medium instead of mentioned sulphur-containing salts strains of this species did not require cystine and assimilated the ammonium nitrogen. The intensity of their growth in these conditions was lower and carbon nutrition spectra more limited than in custine containing medium. Tetrathionate, elemental sulphur, sulphide were less efficient than thiosulphate, but they also provided growth of B. diminuta strains in the media supplied with ammonium salts, necessary vitamins and such universal C sources as aspartate, glutamate, proline. Neither oxidized nor reduced mineral sulphur forms were able to substitute sulphur-containing amino acids for Comamonas terrigena strain requiring methionine. PMID- 11785418 TI - [Effect of Chaetomium cochliodes Palliser on micromycetes of the root zone of spring barley]. AB - The paper deals with the studies in species composition of micromycetes of the meadow-chernozem deleached soil in the root zone of spring barley and their interaction with the strain of fungus-antagonist Chaetomium cochliodes 3250, which served a basis for creation of the preparation--chetomik to protect plants from the root diseases agents. Differences were established between mycobiota of soil and root zone of plants; the most considerable ones are the differences between soil rhizoplane: the decrease of special diversity, changes in the number composition of numerous micromycete species. It has been shown that Chaetomium cochliodes 3250 manifests high antagonistic activity with respect to saprophytic and, especially, phytopathogenic fungi isolated from soil of spaces between rows, rhizosphere as well as rhizoplane of the spring barley which evidences for expediency of this strain use as the means of the culture protection from the root rots. PMID- 11785419 TI - [Study of availability of some hydrolytic and redox enzymes in strains of Fusarium oxysporum (Schlecht.) Snyd. and Hans. isolated from different habitats]. AB - The work authors have used 52 strains of F. oxysporum for the collection of cultures of the Department of Physiology and Taxonomy of Micromycetes of IMV of the NAS of Ukraine. The strains were isolated from three habitats--grain cultures, cultivated and noncultivated soils of different regions of Ukraine. Activity of some hydrolytic (cellulose, endo-1,4-beta-xylanase, beta-glucosidase and amylase) and redox (monophenol-monooxygenase and peroxidase) enzymes of F. oxysporum strains. It has been shown that strains isolated from plant substrates produced more actively hydrolytic enzymes--cellulose, endo-1,4-beta-xylanase and beta-glucosidase. As to the degree of these enzymes activity the studied strains were distributed in the following order: strains from plants (P) > strains from cultivated soil (CS) > strains from noncultivated soils (NS). The soil strains NS > CS > P proved to be more active as to activity manifestation of the redox enzymes (monophenol-monooxygenase and peroxidase). PMID- 11785420 TI - [Search for lectin producers among some yeast species]. AB - Hemagglutinating properties of culture liquid and cells of 142 yeast strains of species Saccharomyces cerevisiae, Kluyveromyces marxianus, K. dobzhanskii, K. lactis var. lactis and K. lactis var. drosophilarum, isolated from various sources have been studied. A capacity of yeast (44% of the studied strains) to synthesize both lectins bound to a cell and extracellular lectins has been established; the latter have been found in yeast for the first time. PMID- 11785421 TI - [Construction of the shuttle vector pSTS1 and development of the method of its introduction into the cells of the cyanbacterium Plectonema boryanum CALU 465]. AB - It has been shown that cells of trichoma cyanobacterium Plectonema boryanum G o m. strain CALU 465 do not possess natural resistance to antibiotics ampicyllin, chloramphenicol, streptomycin and canamycin. A shuttle vector pSTS1 has been constructed on the basis of cyanobacterial plasmid pSM1 and vector pBR 322. Conditions have been developed and conjugative transfer of pSTS1 to the cells of cyanobacterium P. boryanum has been performed. As the result of expression of beta-lactamase gene pSTS1 the resistance of cells-conjugantes to ampicillin increased by three orders. PMID- 11785422 TI - [Effect of plant growth stimulators on Rhizobium leguminosarum BV. VICIAE 263b and efficiency of symbiotic nitrogen-fixation in peas]. AB - Effect of two plant growth stimulators: bactozol (drug of bacterial origin) and D1 (synthetic analog of phytohormones) on metabolism of pea rhizobia (Rhizobium leguminosarum bv. viciae 2636) and efficiency of their symbiosis with pea plants have been studied. The D1 drug in concentration 0.1% suppressed growth of bacteria. However, bactozol stimulating action on pea rhizobia growth in a pure culture and synthesis of extracellular carbohydrates by them have been established. The trial of three concentrations (0.1%, 0.01%, 0.001%) has shown that bactozol effect has dose-dependent character. The highest effect of stimulation is achieved at concentration 0.1%. Bactozol decreases partially the repressing influence of the mineral nitrogen on growth of rhizobia and their carbohydrate-synthesizing activity under growth of bacteria against a high nitrogen background (20 mM NO3-). Treatment of pea plants by bactozol (0.1%) increases considerably the efficiency of their symbiosis with pea rhizobia, evoking the growth of the overground and root mass of the plants, quantity of nodules and their nitrogenase activity. PMID- 11785423 TI - [Study of associate nitrogen fixation in pasture ryegrass]. AB - A direct proof of intensification of associative nitrogen-fixation activity and considerable increase of intake of biological nitrogen by the pasture ryegrass plants, when using low doses of ammonium-carbonate compounds (ACC) as compared with ammonium nitrate (AN) has been obtained with the help of labelled nitrogen 15N. The isotope method confirms a possibility of biological nitrogen-fixation intensification in the mentioned culture when using synthetic plant growth regulator of a new generation Triman-1. More efficient use of ACC and AN by plant has been established. PMID- 11785425 TI - [Biological functions of microbial exopolysaccharides]. AB - The review includes literature data and the author's experimental data concerning the role of microbial exopolysaccharides (EPS) in protection of the producer cells from different unfavourable factors (drying, effect of toxic metals, antibiotics, biocydes, etc), participation of EPS in trophic metabolism of microorganisms (use of EPS as a source of carbon supply, role in regulation of cell ion balance), as well as in interaction of producers with other microorganisms, macroorganisms, objects of inorganic nature (EPS as virulence factor, EPS participation in the processes of adhesion, sorption and aggregation, in formation of plant-bacterial symbioses). A question of interrelation of physico-chemical properties of microbial EPS and their biological functions as well as of these data use in biotechnology for production of polysaccharides with preset properties is discussed. PMID- 11785424 TI - [Sensitivity of urogenital aerobic microflora to antibiotics]. AB - The following aerobic opportunistic bacteria have been isolated in women with different inflammatory processes of the reproductive system: staphylococci--62%, enterobacteria--30%, streptococci--11%, pseudomonads--7%. Gram-positive cocci (staphylococci and streptococci, except for Streptococcus faecium) manifested the highest sensitivity to amoxycillin/clavulanic acid. Clinical isolates of enterobacteria were characterized by high percentage of strains sensitive to cyprofloxacine and cephalosporines of the third generation. The highest number of sensitive strains was registered in fluoroquinolon for Pseudomonas aeruginosa. PMID- 11785426 TI - [Productivity of autotetraploids and frequency of aneuploidy in reproduction in Haplopappus gracilis L]. AB - Comparative studies of productivity of autotetraploid plants H. gracilis L. after selection for high productivity, without selection for high productivity and aneuploidity, and after selection for low productivity have been done. The results show considerable effectiveness of selection for productivity. Presence of hyperaneuploid forms in the population is a major cause of the decreasing of autotetraploid productivity. PMID- 11785427 TI - [Identification of maize genotypes by PCR analysis]. AB - The possibility of identification and differentiation of maize genotypes by means of RAPD-, SSR- and ISSR-methods was analyzed. DNA of 12 inbred lines and 6 corresponding hybrids of maize were used. Presented methods of the PCR-analysis have allowed unique differentiation and identification of maize genotypes. A formula that describes the results of the DNA polymorphism analysis was proposed. PMID- 11785428 TI - [Genetic determination and inheritance of resistance to Fusarium graminearum L. in wheat]. AB - A genetic basis of resistance of winter wheat to Fusarium graminearum causing Fusarium head blight was defined as a result of F1, F2, BC1 hybrid analysis in the crosses of some lines and varieties with highly susceptible variety Odesskaya polukarlikovaya. It was found out that resistance to Fusarium graminearum inherited regardless of resistance to rust, mildew and Septoria. PMID- 11785429 TI - [Differences in the genetic systems controlling photoreaction and vernalization requirements in winter wheat]. AB - Comparing of vernalization requirement and photoperiodic sensitivity in various winter genotypes and F4 lines was carried out. The results of genetic analysis of Ppd genotypes in the crosses of winter wheat cultivars differing in photosensitivity and duration of vernalization requirement are described. It has been shown that differences in duration of vernalization requirement are under control of independent genetic system, distinctive from Ppd gene system regulating level of photosensitivity. This independence does not deny the opposite possibility of Ppd genes to modify duration of vernalization requirement in winter wheat. PMID- 11785430 TI - [Phototaxis and adaptation of the eyeless Drosophila melanogaster line]. AB - An artificial selection on positive and negative phototaxis of eyeless (ey) Drosophila melanogaster line was carried out. Expression of the ey trait in imago was estimating during the selection. The fitness of the "+" and "-" selected lines was evaluated by such components as heat resistance, life span, fertility of flies. The genetic analysis of phototaxis inheritance was carried out. It was found that phototaxis selection results in changes of fertility whereas it doesn't affect other indices of fitness to environmental conditions as well as the ey expression. The main polygenic systems of phototaxis inheritance are located in chromosome 2 and chromosome 3. PMID- 11785431 TI - [Structural characteristics of osteopontin mRNA]. AB - Conservatism of primary and secondary structure of osteopontin mRNA in vertebrates of various taxes was studied using computer analysis and blot hybridization procedure. Relatively high rate of evolution of a nucleotide sequence of osteopontin gene was revealed. Formation of hairpin-loop structures by adjacent sequences and a high content of AU-pairs indicate more flexible structure of the mammalian osteopontin mRNA as compared with the avian one. It has been detected some AU-enriched regions in 3'-terminal untranslated sequences, which presence is characteristic for short-lived mRNA. Evolutionary conserved subsequences in 3'- and 5'-terminal regions were suggested to be determinants of RNA-protein interaction in cytoplasm. PMID- 11785432 TI - [DNA diagnosis of porcine stress syndrome and RYRI genotype association with viability of young pigs]. AB - A technique of rhyanodinreceptor gene (RYRI) typing was improved and applied for diagnostics of porcine stress syndrome. Genetic population analysis with respect to RYRI gene in the pigs of various breeds was made. Maximal distribution of the RYRI T-allele was observed in the Poltava Meaty pig population. No mutation alleles were revealed in the animals of Large White and Mirgorod breeds. Adequacy of the DNA diagnostic test to the classical halothane one was shown. Association of genotypes by rhyanodinreceptor gene with viability of young pigs was found. PMID- 11785433 TI - [Complex estimation of proliferative activity of epithelial cells of the large intestine damaged by polyps and cancer]. AB - Peculiarities of mitotic regime and expression of proliferating cell nuclear antigen were investigated in 18 polyps and 35 cases of colorectal cancer. Direct relationship between spectrum and degree of manifestation of proliferative activity, level of morphological malignant tumors and accumulation of oncopathology in the patient pedigrees was established. PMID- 11785434 TI - [Spontaneous frequency of micronuclei in peripheral blood lymphocytes of Kiev residents]. AB - The level of micronuclei in the peripheral blood lymphocytes of Kyiv residents and its dependence on age, sex and smoking status were studied. Analysis of lymphocytes of 102 healthy Kyiv residents showed that the spontaneous frequency of micronuclei in individuals at the age of 21 to 67 (mean age of 42.6) was 10.5 +/- 0.5@1000. The frequency of micronuclei depends on individual age and increases by 3% per year, and also depends on smoking habits (the micronucleus frequency in smokers was 1.3 times higher then nonsmokers). There is no dependence of the micronucleus frequency on the sex of persons. PMID- 11785436 TI - [Gene pool of the population of Ukraine: Current state and new approaches to maintenance and conservation]. AB - Defense and conservation of the Ukraine Population genofond are the most topical problem of nowadays. Stating of the criteria of population genofond status valuation, revealing all the damaging factors and applying of scientific methods of modern genetics are necessary for the development of theoretical and methodological bases of this problem. The authors try to analyze in detail negative factors causing damage in genofond of the Ukraine population, to forecast the dynamics of further development of ecological-genetic situation in the Ukraine, to analyze new approaches to the problem of genofond defense and conservation, as well as estimation of possible consequences caused by changes in population genofond. PMID- 11785435 TI - [Biomonitoring of lymphocytes of workers exposed to nickel compounds and an approach to reduction of genetic effects]. AB - While examining the workers of the fire nickel production contacting preferably with insoluble and weakly soluble compounds of nickel, inhibition of DNA repair and increased level of chromosome changes (micronucleus test) were detected. Decreasing of micronucleus number, which was higher in smokers, and tendency to the stimulation of DNA repair synthesis were revealed after 1-month course of ascorbic acid (1 g/day). A level of changes in chromosome structure in the control group was estimated using the index of sister chromatid exchanges (SCE): variation of initial values was in normal bounds (6-8 SCE per cell), after vitamin course it even slightly decreased. High individual variability of chromosome changes and susceptibility to ascorbic acid was found. PMID- 11785437 TI - [Role of the nucleolus in plant cell response to environmental physical factors]. AB - Contemporary data on ultrastructural reconstruction and changes in functional nucleolus activity in plant cells affected by physical environmental factors are presented. The main attention is paid to modifications of ribosomal gene expression under these conditions and induced changes in r-chromatin structure and ribosomal DNA localization. Recent data on fine nucleolus structure and molecular aspects of its organization as well as influence of microgravitation and clinostating on structural and functional organization of plant nucleoli are reported. PMID- 11785438 TI - Nursing in health care reform. PMID- 11785439 TI - Comparison of the FemoStop device and manual pressure in reducing groin puncture site complications following coronary angioplasty and coronary stent placement. AB - This study compared two techniques, the FemoStop device (RADI Medical Systems, Uppsala, Sweden) and manual pressure, currently used by nurses to achieve haemostasis at the groin puncture site following removal of femoral arterial sheaths in patients following coronary angioplasty and coronary stent placement. Participants were randomly allocated the FemoStop device or manual pressure. Participants' groins were observed for evidence of complications including haemorrhage, haematoma formation and pseudoaneurysm following removal of the femoral arterial sheath and the following day. Of the 274 participants recruited into the study, 5.5% (n = 15) were unable to be included as a result of the absence of data on the Angioplasty Record of Care Form (n = 5) or excessive bleeding at the groin puncture site (n = 10). This left 259 eligible participants. Of these, 18.1% (n = 47) did not have their groin puncture site inspected by a post-procedural observer, thereby reducing the number of participants eligible to complete all stages of the study to 212. The results showed that the presence of a haematoma on removal of the femoral arterial sheath had a significant relationship with the type of treatment used, with those participants in the FemoStop device group showing a greater incidence of haematoma development at the time of sheath removal than those in the manual pressure group. No significant difference was detected in haematoma formation or bleeding between the two groups as a result of the risk factors identified in the literature, including participant anxiety, weight or anticoagulant therapy. There was not any significant difference between the two groups in reported pain during removal of the femoral arterial sheath; however, there was a significant distinction in the amount of time taken to achieve haemostasis. The results showed that haemostasis was achieved more quickly in those participants in the manual pressure group than those in the FemoStop group. The results of this research study indicate that although manual pressure achieved haemostasis more quickly than the FemoStop device, both methods are as effective in reducing groin complications in patients following removal of the femoral arterial sheath following coronary angioplasty and stent placement. PMID- 11785440 TI - Elements of a systematic review. AB - This paper examines the subject of systematic reviews from a nursing viewpoint. The history of the evidence-based healthcare movement and the major differences between systematic reviews and traditional literature reviews are discussed. The steps of the process used by those conducting reviews are examined in detail. These include structuring a research question, searching and appraising the literature, data extraction, analysis and synthesis, and reporting the results. It is this process that ensures reviews can be considered as a legitimate form of nursing research. PMID- 11785441 TI - Inequalities in health: evaluation and effectiveness in practice. AB - This paper details the findings from a project that assessed the contribution made by nurses, midwives and health visitors to targeting health and social need. This is an important theme within the Northern Ireland Regional Strategy entitled 'Health and well-being into the next millennium: a regional strategy for health and social well-being 1997-2002', which is concerned with addressing inequalities in health status and social well-being. In response to this initial survey, the paper also highlights the second phase of the project that was the development of an evaluation manual specifically designed to assist health-care practitioners in establishing evaluation frameworks and in applying evaluation techniques and methods. The paper describes four research case studies that are intended to illustrate the kinds of evaluation methods necessary to cover the stages of evaluation, needs assessment, structure, process and outcome, and to reflect the experience of applied evaluation as it occurs in practice as opposed to how it appears in textbooks. PMID- 11785442 TI - Approaches used to implement research findings into nursing practice: report of a study tour to Australia and New Zealand. AB - The focus of the study tour to several research and nursing units in Australia and New Zealand (NZ) was to investigate what has influenced the way nurses implement research into practice. The key areas examined were strategic policy influences, activities within leading academic units and responses in practice areas. The main themes to emerge were that the strategies developed by health policy makers in Australia and New Zealand have been profoundly influenced by the global clinical effectiveness and evidence-based practice movements. Nursing needs to position itself firmly in the centre of such developments and leading nursing initiatives need to be mainstreamed into the wider evidence-based movement. While activity around clinical/practice guideline development moves on, more work needs to be done to understand how best to actually implement research in practice. Issues of organizational context, ownership, practice, culture and identifying local champions are emerging as key challenges for the next stage of implementation. Much can be learnt from ongoing dialogue. PMID- 11785443 TI - Identifying and transforming dysfunctional nurse-nurse relationships through reflective practice and action research. AB - This project facilitated reflective practice processes in experienced Registered Nurses (RNs) in order to raise critical awareness of practice problems, work systematically through problem-solving processes to uncover constraints, and improve the quality of care given by nurses in light of the identified constraints and possibilities. Twelve experienced female RNs working in a large Australian rural hospital shared their experiences of nursing during three action research cycles. A thematic concern of dysfunctional nurse-nurse relationships was identified, as evidenced by bullying and horizontal violence. The negotiated action plan was put into place and participants reported varying degrees of success in attempting to improve nurse-nurse relationships. PMID- 11785444 TI - Mental health literacy survey of psychiatrically and generally trained nurses employed in a Singapore psychiatric hospital. AB - Mental health literacy studies consider the capacity of respondents to recognize certain psychiatric disorders, judge the comparative utility of a range of interventions, and make estimates about outcome and prognostic issues. We report such a study involving a sample of nursing staff employed at a large psychiatric institution in Singapore, and who were provided with separate brief vignettes of mania, schizophrenia and depression. Subjects were highly accurate in 'diagnosing' schizophrenia, less accurate for depression and even less accurate in diagnosing mania. Depression was alternately diagnosed as stress, mania was most commonly misdiagnosed as schizophrenia, and for both psychotic conditions, a percentage returned non-psychotic diagnoses. In terms of treatment options, staff distinctly favoured a 'medical model' and viewed traditional and alternative healing options as distinctly harmful. Analyses contrasted psychiatrically trained and generally trained nurses, but identified few significant differences. Such information has the potential to shape the education and training of mental health professional staff, as well as provide important insights about how nurses may diagnose, view and favour alternative treatments and strategies to assist those with common psychiatric disorders. PMID- 11785445 TI - Knowledge, assessment and management of pain related to nursing procedures used with premature babies: questionnaire study for caregivers. AB - The aim of the study was to discover how much Finnish nursing staff know about the pain experienced by premature babies and about pain assessment. The types of helping methods used by caregivers in the nursing of premature babies were also studied. A semistructured questionnaire was sent in autumn 1995 to all registered nurses, practical children's nurses and medical laboratory technologists who take heel blood samples (n = 280) working in paediatric intensive care units in all Finnish university hospitals. The response rate was 70.4%. The structured questions were processed quantitatively at Kuopio University with the SPSS/PC+ data processing program (SPSS, Chicago, IL, USA), and the open questions were processed using quantitative content analysis. The results indicate that the respondents have rather extensive knowledge about the pain experienced by premature babies, pain assessment, pain management and about nursing and helping methods. Pain was assessed mostly on the basis of behaviour and physiological changes, and only infrequently on the basis of biochemical changes. The respondents described the helping methods they use in considerable detail. The most common was to increase the baby's feeling of security. The answers to the open questions revealed that the actions used by the respondents in pain assessment and pain management were not completely consistent with their knowledge. The results demonstrate that caregivers do not use their knowledge adequately in their pain management practices. Future studies should observe the three groups of caregivers in order to discover how they treat premature babies' pain. PMID- 11785446 TI - Influence of self-efficacy and other factors on dietary behaviours in Japanese haemodialysis patients. AB - In Japan, haemodialysis patients are required to adhere to a fairly rigid dietary regimen. Guided by Bandura's theory of self-efficacy, this study tested a prediction model of dietary behaviour. A total of 325 individuals completed a self-administered survey containing nine scales, which were used to measure the six constructs in the model. Using multiple regression analysis, 24% of the variance on the Dietary Behaviour Scale could be accounted for by three predictor scales, Dietary Management Self-efficacy, Support from Family, and Self Repressive Behaviour Patterns. Multiple regression analysis identified that four scales, Character Image of Dialysis Staff, Support from Family, Dialysis Acceptance, and Somatic Symptoms, contributed to 13% of the variance of the Dietary Management Self-efficacy Scale. These results might provide direction to those who are involved in the support and care of haemodialysis patients, some of whom require life-long treatment, as is common in Japan. PMID- 11785447 TI - A global view of nursing in the new millennium--6: Aspirations of nurses. PMID- 11785448 TI - A pilot study on the role of cytomegalovirus & human herpesvirus-6 infections in Indian bone marrow transplant recipients. AB - BACKGROUND & OBJECTIVES: Studies from Western transplant centers have shown the importance of cytomegalovirus (CMV) in infections among immunosuppressed post transplant patients (both solid and bone marrow transplant recipients). Human herpesvirus-6 (HHV-6) infection is also important. Since such data are lacking from India, we carried out a pilot study to investigate the role of these two viruses in infections among Indian allogeneic bone marrow transplant (BMT) recipients. METHODS: A total of 21 BMT patients who developed acute graft versus host disease (GVHD), two patients who developed chronic GVHD, and eight recipients who did not develop GVHD but had skin rash/elevated liver enzymes, persistent cytopaenia or interstitial pneumonitis with a high clinical suspicion of possible CMV association were studied for markers of CMV and HHV-6 infections. RESULTS: CMV DNAemia was documented in 9 (42.8%) and CMV IgM in 4(19%) of the 21 patients with acute GVHD. HHV-6 DNAemia was not seen in any patient with acute GVHD but 2 (9.5%) had HHV-6 IgM. Of the 2 patients with chronic GVHD, 1 was positive for CMV DNA and IgM, and both were negative for HHV-6 markers. The lower incidence of CMV DNAemia in our recipients may be attributable to the presence of neutralizing antibody (anti gB/AD-1) among the 17 CMV and HHV-6 DNAemia negative recipients, 4(23.5%) had neutralizing antibodies (S/N ratio > or = 5). Of the 13 CMV DNAemia positive recipients, only one (7.7%) was positive for neutralizing antibodies. Among the 5 neutralizing antibody (S/N ratio > or = 5) positive recipients, 4 (80%) were negative for CMV DNAemia. The one nPCR positive was revealed only at high DNA (> 0.1 microgram) input indicating low CMV signal strength. INTERPRETATION & CONCLUSION: The present study shows the use of DNAemia in detecting CMV infections among BMT recipients. All recipients had high avidity CMV IgG (AI > 50%) confirming CMV reactivation or reinfection in these patients. There was evidence from this study suggesting that neutralizing antibodies may play a role in controlling CMV reactivation. We found no significant HHV-6 association with GVHD in Indian allogeneic BMT recipients. PMID- 11785449 TI - Rapid assay for detection of chloramphenicol acetyl transferase in Haemophilus influenzae. AB - BACKGROUND & OBJECTIVES: Haemophilus influenzae causes a variety of life threatening infections in humans. Early detection of antimicrobial resistance is of importance in the treatment and management of infection. The modified Slack's method, a simple assay, has been evaluated in this study for the early detection of chloramphenicol resistance. METHODS: Fifty isolates of H. influenzae from invasive and non-invasive sites were included. Antimicrobial susceptibility testing was done by disc diffusion method and minimum inhibitory concentration (MIC) determination was performed for chloramphenicol only. Modified Slack's method was used to test for the production of chloramphenicol acetyl transferase (CAT). RESULTS: Invasive isolates showed higher degree of resistance to chloramphenicol (72%) compared to non-invasive ones (28%). One hundred per cent association was found between results of disc diffusion, MIC and CAT production amongst strains resistant to chloramphenicol. INTERPRETATION & CONCLUSION: The findings suggested that chloramphenicol still remains the drug of choice for treatment for non-invasive infection caused by H. influenzae. Modified Slack's method is a simple, rapid, inexpensive and reliable method for the detection of chloramphenicol resistance amongst H. influenzae. PMID- 11785450 TI - An indirect ELISA for the diagnosis of melioidosis. AB - BACKGROUND & OBJECTIVES: Very little information is available on melioidosis in India. This disease caused by Burkholderia pseudomallei is not often considered as a differential diagnosis and patients are not usually investigated for it. Thus we are unaware of its prevalence in India. This study was undertaken to detect the presence of melioidosis in patients presenting with pyrexia of unknown origin (PUO) using an indirect ELISA. METHODS: The well established ELISA technique was adapted to detect melioidosis in patients attending the Christian Medical College and Hospital, Vellore and to provide a serological test using reagents with a reasonable shelf-life. The ELISA is designed to detect IgG antibodies to B. pseudomallei in serum samples. RESULTS: A cut-off optical density (OD) of 0.36 (mean +/- 2 SD of healthy controls) was chosen as diagnostic criterion for the diseased group. The mean OD values in the sera of patients with culture proven melioidosis was significantly (P < 0.001) higher than that of healthy controls. INTERPRETATION & CONCLUSION: The indirect ELISA was simple to perform and may be recommended as a diagnostic serological test when melioidosis is considered as a differential diagnosis. PMID- 11785451 TI - Evaluation of darkground microscopy as a rapid diagnostic procedure in leptospirosis. AB - BACKGROUND & OBJECTIVES: Although darkground microscopy (DGM) is the method employed for examining the growth of leptospires in culture, it is not useful for diagnosis when used directly on body fluids. However, it continues to be used as a method for diagnosing leptospirosis in many centres in India. The present study was undertaken to evaluate the diagnostic accuracy of DGM by comparing it with established tests like culture, microscopic agglutination test (MAT), IgM ELISA and Lepto-Dipstick. METHODS: A total of 170 patients clinically suspected to have leptospirosis were included in the study. The gold standard for diagnosis was positive blood culture, or seroconversion, or a four-fold rise in titre in MAT. DGM was done on plasma after centrifugation at 1000 g and 3000 g and on serum. Indices of accuracy including sensitivity, specificity, predictive values and kappa value of agreement with the gold standard diagnostic criteria were calculated. RESULTS: DGM had a sensitivity of 40.2 per cent, specificity of 61.5 per cent, a positive predictive value of 55.2 per cent and a negative predictive value of 46.6 per cent. It had agreement with the gold standard in only 50 per cent cases the kappa value being 0.017141. INTERPRETATION & CONCLUSION: DGM has low indices of accuracy. The results obtained in patients who met the gold standard criteria for diagnosis and those who did not were identical indicating that the test results are not determined by the presence of leptospiral infection in the patient. DGM, therefore, is not recommended as a sole diagnostic procedure for early diagnosis of leptospirosis. PMID- 11785452 TI - Laboratory evaluation of Ssp I PCR assay for the detection of Wuchereria bancrofti infection in Culex quinquefasciatus. AB - BACKGROUND & OBJECTIVES: There is a need to delimit the areas of filariasis transmission in view of the Filariasis Elimination Programme launched in India. Infection rate in vectors is an important parameter in determining transmission and it is conventionally assessed by dissection and microscopy. A PCR assay based on Ssp I repeats of Wuchereria bancrofti has shown potential in the detection of infection in vectors. The aim of the present study was to evaluate the specificity and sensitivity of this assay on W. bancrofti and its vector, Culex quinquefasciatus, prevalent in India. METHODS: The DNA from pools of C. quinquefasciatus to which W. bancrofti microfilariae (mf) were added, was extracted by lysing with 0.1 M NaOH and 0.2 per cent sodium dodecyl sulphate (SDS), followed by silica absorption in the presence of guanidinium thiocyanate. The PCR assay of the DNA samples was carried out using NV-1 and NV-2 primers and the species specific SspI band was visualized on agarose gels stained with ethidium bromide. RESULTS: The Ssp I PCR assay was found to be highly species specific, as it did not detect the DNA of a closely related filarial parasite, Brugia malayi. The assay detected as little as 0.04 pg of W. bancrarofti DNA. Minimum number of parasite detectable in pools of mosquitoes was 1 mf. A pool size of 50 mosquitoes was found to be optimum for the PCR assay. INTERPRETATION & CONCLUSION: The Ssp I PCR assay was found to be highly specific and sensitive in detecting filarial parasite in pools of mosquitoes and therefore has potential application in rapid assessment of transmission of filariasis. PMID- 11785453 TI - A clinico-epidemiological perspective of lymphatic filariasis in Satyabadi block of Puri district, Orissa. AB - BACKGROUND & OBJECTIVES: Lymphatic filariasis is a major public health problem in the coastal district of Orissa. However, no systematic studies have been done to document the prevalence of microfilaraemia/disease in different regions of the State. Therefore, the present cross sectional study was undertaken during 1996-97 to obtain information on the clinical and epidemiological status of the disease in Satyabadi block area of Puri district, known to be endemic for filariasis. METHODS: Night blood smear survey and clinical examinations were performed on 4646 individuals aged 0-> or = 60 yr from systematically selected households of 17 randomly selected villages of the Block. Microfilaraemia was detected by thick drop technique using 20 microliters of peripheral blood and microfilariae (mf) density by nucleopore filtration technique collected during 1900-2300 h. RESULTS: The prevalence of microfilaraemia was observed to be 14.8 per cent; 13.3 per cent Wuchereria bancrofti, 1.4 per cent Brugia malayi and 0.09 per cent had mixed infections. Geometric mean microfilaraemia density (infected persons only) was found to be 1288 per ml in case of W. bancrofti and 204 per ml in case of B. malayi. The disease rate was observed to be 19.8 per cent; 12.85 per cent had acute manifestations and 6.97 per cent had chronic manifestations. INTERPRETATION & CONCLUSION: The rate of acute disease manifestations was observed to be significantly higher (P < 0.001) than chronic manifestations. There was a male preponderence among the affected individuals (P < 0.001). The interesting observations of the study were the occurrence of occult filarial manifestations viz., tropical pulmonary eosinophilia (TPE) in 0.47 per cent cases and other associated manifestations like asymptomatic microscopic haematuria, monoarticular arthritis and filarial associated respiratory diseases in 0.50, 0.24 and 0.19 per cent of cases respectively. The present study indicates that the area is highly endemic for lymphatic filariasis with active transmission. PMID- 11785454 TI - 92nd Annual Meeting of the American Association for Cancer Research. 24-28 March, 2001, New Orleans, Louisiana, USA. AB - The 92nd Annual Meeting of the AACR comprised over 5000 abstracts, 12 plenary and award lectures and numerous talks in educational sessions, symposia and mini symposia. Given the wealth of information presented, we narrowed our coverage to the area of prenyltransferase and protein kinase inhibitors. Many rationally designed drugs are now in clinical trials and exciting results were presented for the Bcr-Abl inhibitor STI-571. The cancer community is beginning to envision new ways to evaluate and administer these well-tolerated drugs which do not fit the traditional anticancer drug profile. There is an emphasis in developing surrogate markers for evaluating the mechanism-based effectiveness as well as identifying off-target toxicities. In addition, there is a large effort in investigating effective drug combinations and the use of these new agents as radiosensitisers. Here we present specific examples of these issues as applied to prenylation and protein kinase inhibitors. PMID- 11785455 TI - A small-molecule antagonist of virion assembly. PMID- 11785456 TI - A daughter of bradykinin that protects against septicaemia. AB - When the defence response of the body to infectious bacteria fails, septic shock ensues with hypotension and death. RPPGF,(1-5)-bradykinin, was until recently considered to be an active metabolite of bradykinin. In an animal model of septicaemia (lipopolysaccharide administration to rats), RPPGF is protective, and can even prolong life. RPPGF, or stable mimetics, have potential in the treatment of septic shock. PMID- 11785457 TI - Trichostatin A, an inhibitor of histone deacetylase, inhibits hypoxia-induced angiogenesis. AB - Trichostatin A (TSA), a hydroxamate-type inhibitor of mammalian histone deacetylases has been reported to inhibit angiogenesis both in vitro and in vivo. TSA inhibits hypoxia-induced production of the angiogenic mediator vascular endothelial cell growth factor (VEGF) by tumour cells and also inhibits directly endothelial cell migration and proliferation. HDAC inhibitors such as TSA are currently of major interest as potential anticancer therapeutics, largely because of their well-documented properties of inhibiting proliferation and inducing apoptosis of tumour cells. The finding that HDAC appears to be a critical regulator of angiogenesis in addition to tumour cell growth will heighten interest in the development of HDAC inhibitors as potential anticancer drugs. PMID- 11785458 TI - American Society of Microbiology 101st General Meeting. 20-24 May 2001, Orlando, FL, USA. AB - The application of sophisticated molecular biology, genetics and genomics has made possible the advanced analyses of microbial genes, the topology of DNA and chromosomes, and insight into the regulation of gene expression during all stages of the life cycle of microbes, both in vitro and in vivo. The struggle to control contagious pathogens continues world wide amidst resistance emergence to many classes of antimicrobial agents. Many hospital, research and community labs are applying themselves to a more thorough understanding of the molecular basis of this resistance. New drugs which improve on predecessor agents were presented. The following classes of antimicrobial agents were represented: quinolones, cephems, macrolides and natural products. New target opportunities against both lethal (essential) gene targets and virulence targets were presented throughout the conference. In addition, increasing attention to the involvement of microbial life forms in immune function and dysfunction were described in numerous presentations. PMID- 11785459 TI - Web Watch. PMID- 11785460 TI - [The 29th annual meeting of the Japanese Society of Clinical Immunology. Osaka, Japan. December 10-11, 2001. Abstracts]. PMID- 11785461 TI - Deploying our forces. PMID- 11785463 TI - MTCT meeting in Uganda ends with criticism of politicians. PMID- 11785462 TI - HIV news from Buenos Aires: Part 2--symmetries and semistops. PMID- 11785464 TI - Giving never lessens the purse. PMID- 11785465 TI - Viro diversity (or, keeping up with HIV's evolutionary caprice). PMID- 11785466 TI - Declaration of commitment on HIV/AIDS. "Global crisis--global action.". PMID- 11785467 TI - [Nobel Prize will be 100 years old. Emil von Behring: the first medicine laureate]. PMID- 11785468 TI - Approach to assay validation for the development of biopharmaceuticals. PMID- 11785469 TI - Summaries for patients. Special diets decrease blood pressure. PMID- 11785470 TI - Summaries for patients. Newspaper reporting about mammography to screen for breast cancer. PMID- 11785471 TI - Summaries for patients. Musculoskeletal pain and the progression of disability among older women with disability. PMID- 11785472 TI - Summaries for patients. Quinine and thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. PMID- 11785473 TI - Small town, big misperceptions. PMID- 11785474 TI - Detection and treatment of depression. PMID- 11785475 TI - Preventing depression. PMID- 11785476 TI - Living with HIV--a survivor's perspective. PMID- 11785477 TI - Sustiva "dirty drops" put prisoners in solitary. PMID- 11785478 TI - Rescue regimens: the value of PI boosting. PMID- 11785479 TI - Abusive behaviors and HIV. PMID- 11785480 TI - God breast ye merry gentlemen. PMID- 11785481 TI - Affordable drug access for developing countries. PMID- 11785482 TI - Osteoporosis and HIV disease. PMID- 11785484 TI - AIDS vaccines: the ethical and societal issues. PMID- 11785483 TI - Adolescent sexuality, gender, and the HIV epidemic. PMID- 11785486 TI - Full-body CT scans. What you need to know. PMID- 11785487 TI - Beat the winter bugs. How to hold your own against colds and flu. PMID- 11785488 TI - Home diagnostic tests: the ultimate house call? PMID- 11785489 TI - Alternatives to hysterectomy. New technologies, more options. PMID- 11785490 TI - Living with AIDS--20 years later. PMID- 11785492 TI - Living with the enemy: never letting our guard down. PMID- 11785491 TI - California man convicted for brewing a coffee scam. PMID- 11785493 TI - Encouraging women to take charge of diabetes. PMID- 11785494 TI - HHS responds to terrorist attacks. PMID- 11785495 TI - Anthrax prevention and treatment. PMID- 11785496 TI - Classification system for malformations of cortical development: update 2001. AB - The many recent discoveries concerning the molecular biologic bases of malformations of cortical development and the discovery of new such malformations have rendered previous classifications out of date. A revised classification of malformations of cortical development is proposed, based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories have been created based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In many cases, the precise developmental and genetic features are uncertain, so classification was made based on known relationships among the genetics, pathologic features, and neuroimaging features. A major change since the prior classification has been the elimination of the separation between diffuse and focal/multifocal malformations, based on the recognition that the processes involved in these processes are not fundamentally different; the difference may merely reflect mosaicism, X inactivation, the influence of modifying genes, or suboptimal imaging. Another change is the listing of fewer specific disorders to reduce the need for revisions; more detail is added in other smaller tables that list specific malformations and malformation syndromes. This classification is useful to the practicing physician in that its framework allows a better conceptual understanding of the disorders, while the component of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications. PMID- 11785497 TI - Intracranial hemorrhages associated with sumatriptan. PMID- 11785498 TI - Authorship designation and the Journal of Child Neurology in 2002. PMID- 11785499 TI - Benign idiopathic partial epilepsies in infancy. AB - In infancy, partial epilepsies have been considered with suspicion for their probable association with brain lesions. Japanese authors first described partial epilepsies in infancy with a favorable outcome and called them benign partial epilepsy in infancy with complex partial seizures. Similar, but familial, cases with onset during the first year of life were described some years later and called benign infantile familial convulsions. Similar familial cases with subsequent choreoathetosis were described in 1997 and called infantile convulsions and choreoathetosis. Benign infantile convulsions have also been described in association with mild gastroenteritis. Interictal electroencephalography (EEG) was always normal in all of these forms. More recently, a new epileptic syndrome characterized by partial seizures with onset between ages 13 and 30 months, a benign outcome, and characteristic EEG abnormalities in the vertex regions during sleep has been described. There is also an early-onset benign childhood occipital seizure susceptibility syndrome that can start in infancy. PMID- 11785500 TI - Sphenoid sinusitis masquerading as migraine headaches in children. AB - The sphenoid sinus is often referred to as the "neglected sinus." Isolated sphenoid sinusitis is a rare disease with potentially devastating complications. It occurs at an incidence of about 2.7% of all sinus infections. Although headache is the most common presenting symptom, there is no typical headache pattern. Three cases of children with isolated sphenoid sinusitis presenting with acute, subacute, and chronic headache symptoms are presented. The sensory innervation of the sphenoid sinus is derived from the ophthalmic and maxillary branches of the trigeminal nerve, which may explain the pathophysiology of the headache, similar to the trigeminovascular pain theory of migraine. There are few reports on sphenoid sinusitis and headache; however, modern neuroimaging has made this probably under-recognized disorder easier to diagnose and treat. Although the diagnosis can be difficult to differentiate from migraine headache, early and appropriate treatment usually results in an excellent outcome without morbidity. PMID- 11785501 TI - Study of influenza-associated encephalitis/encephalopathy in children during the 1997 to 2001 influenza seasons. AB - The 1997 to 2001 influenza A epidemics in Japan were markedly neurovirulent, and many children died of influenza-associated encephalitis/encephalopathy. We studied 20 patients with influenza-associated encephalitis/encephalopathy during the last four influenza seasons. No patients had been previously inoculated with influenza vaccine. Antipyretics were used in 16 patients before the onset of encephalopathy. Although all patients were treated intensively, 5 patients died and 8 had neurologic sequelae. Patients with coagulopathy, hepatic dysfunction, and computed tomographic abnormalities had a poor prognosis. The plasma concentrations of inflammatory cytokines were variable. The neuroradiologic findings could be divided into four categories. These findings indicated that the pathogenesis of the brain damage induced by influenza infection was variable. Further investigation is necessary to determine whether insufficient influenza vaccination or the use of antipyretics is one of the reasons for these epidemics of encephalopathy in Japanese children. PMID- 11785502 TI - Subjective reactions of children to single-pulse transcranial magnetic stimulation. AB - Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children's subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings. PMID- 11785503 TI - Tissue inflammatory response in subacute sclerosing panencephalitis (SSPE). AB - The pattern of inflammatory infiltration was studied in the frontal brain biopsies of 28 cases with subacute sclerosing panencephalitis (SSPE) by immunohistochemistry. Lymphocytic infiltration and gliosis were common pathologic findings. CD4+ T lymphocytes were often observed in perivascular areas and CD8+ lymphocytes in the parenchyma. B lymphocytes were located in large perivascular cuffs associated with longer and slower disease. Major histocompatibility complex antigens, interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) were expressed in endothelial and glial cells. The inflammatory lesions in subacute sclerosing panencephalitis consist of various cell subtypes and cytokines localized in particular areas of the brain tissue and show certain associations with clinical course. PMID- 11785504 TI - Evidence of a specific vulnerability for deficient sequential cognitive information processing in epilepsy. AB - The aim was to study sequential versus simultaneous cognitive information processing and their relation to acquired intellectual abilities in children with epilepsy. A total of 175 children with epilepsy (mean age 8.7 years; SD 2.9) were neuropsychologically examined on the basis of the Kaufman Assessment Battery for Children (K-ABC). To avoid confoundation with factors other than epilepsy, patients with underlying metabolic disorders or patients who were incapable of neuropsychologic testing because of severe mental retardation were excluded. We found significantly reduced cognitive processing, especially in sequential information processing compared with simultaneous information processing (mean score 85.9 versus 91.0). This selective impairment in sequential cognitive processing turned out to be a good statistical predictor for acquired abilities in the group of idiopathic epilepsy (beta = 0.53; P < .01), indicating a specific epileptic neuropsychologic association. Our findings provide evidence of a specific vulnerability for deficient sequential information processing presumably impairing academic achievement in childhood epilepsy. PMID- 11785505 TI - Acute gastroenteritis-related encephalopathy. AB - We studied the incidence of convulsions in 1936 children with acute gastroenteritis. Sixty-eight children had convulsions (3.5%), which were categorized into three groups: (1) bacterial (n = 13; 19%), (2) Rotavirus (n = 30, 44%), and (3) no organism (n = 25; 37%). Only group 2 versus group 3 had a significant association with encephalopathy (P < .002). The relative risk was estimated to determine the risk of encephalopathy: Rotavirus versus no organism isolated (relative risk = 2.308), Rotavirus versus bacterial (relative risk = 1.846), and bacterial versus no organism (relative risk = 1.25). None developed epilepsy. Thus, acute gastroenteritis-related encephalopathy is a benign condition with single or recurrent seizures during an episode of acute gastroenteritis and an excellent prognosis. The underlying mechanism for provoking seizure is unknown. One should be reassured of a good outcome in the majority of children with recurrent episodes of afebrile/febrile seizures during an episode of acute gastroenteritis. PMID- 11785506 TI - Pervasive developmental disorders and GABAergic system in patients with inverted duplicated chromosome 15. AB - Pervasive developmental disorders are characterized by severe, pervasive impairment in several areas of development, with distorted communication skills and stereotypical behavior. Pervasive developmental disorders have a heterogeneous etiology related to brain damage, familial affective psychopathology, chromosomal abnormalities, or dysfunction of neuromodulators. Recently, it has been suggested that the GABRB3 gene, located within chromosome 15q11-13, is a candidate for pervasive developmental disorder. In inverted duplicated chromosome 15 syndrome, in which there is a small marker chromosome derived from inversion and duplication of the chromosome 15q11-q13 region, all patients present with pervasive developmental disorder. To further investigate a possible involvement of the gamma-aminobutyric acid (GABA)ergic system in the inverted duplicated chromosome 15 syndrome, we evaluated plasma levels of GABA and diazepam binding inhibitor in 6 patients with inverted duplicated chromosome 15 and in 8 subjects not affected by neurologic disease. Our findings do not seem to support this hypothesis as no significant differences were found in the GABA and diazepam binding inhibitor plasma levels between patients with inverted duplicated chromosome 15 and controls, but we must consider the possibility that a genetic abnormality of the GABA(A) receptor could be present in patients with inverted duplicated chromosome 15 and still not be reflected in an alteration in either GABA or diazepam binding inhibitor levels in plasma. PMID- 11785507 TI - Pervasive seizures caused by hypoxic-ischemic encephalopathy: treatment with intravenous paraldehyde. AB - Seizures are commonly associated with hypoxic-ischemic encephalopathy. Although the majority of cases are controlled with first- or second-line therapy, others develop pervasive seizures, requiring multiple anticonvulsants. To provide data on the incidence of seizures and response to anticonvulsant therapies, a cohort of 90 term infants with hypoxic-ischemic encephalopathy treated at our institution between January 1, 1995, and July 1, 1999, was reviewed. Of the 60 infants who developed seizures, 59 received phenobarbital initially; in 29 cases, the seizures resolved. The remaining 30 infants received phenytoin as a second line anticonvulsant, and seizures stopped in 10 cases. The 20 infants with ongoing pervasive seizures were treated with intravenous paraldehyde. PMID- 11785508 TI - Neuropathologic research strategies in holoprosencephaly. AB - Hypotheses are presented to explain the pathogenesis of several clinical features of holoprosencephaly, and neuropathologic approaches to testing these hypotheses are suggested. The traditional morphologic classification of holoprosencephaly into alobar, semilobar, and lobar forms is grades of severity, and each occurs in all of the genetic mutations known. Of the four defective genes identified as primary in human holoprosencephaly, three exhibit a ventrodorsal gradient of expression (SHH, SIX3, and TGIF) and one a dorsoventral gradient (ZIC2). But, in addition to the vertical axis, genes expressed in the neural tube also may have rostrocaudal and mediolateral gradients in the other axes. These other gradients may be equally as important as the vertical. If the rostrocaudal gradient extends as far as the mesencephalic neuromere, it may interfere with the formation, migration, or apoptosis of the mesencephalic neural crest, which forms membranous bones of the face, orbits, nose, and parts of the eyes, and may explain the midfacial hypoplasia seen in many, but not all, children with holoprosencephaly. This rostrocaudal gradient also causes noncleavage of the caudate nucleus, thalamus, and hypothalamus and contributes to the formation of the dorsal cyst of holoprosencephaly, which is probably derived from an expanded suprapineal recess of the 3rd ventricle with secondary dilation of the telencephalic monoventricle and at times may produce a unique transfontanellar encephalocele. The extent of the mediolateral gradient may explain the severe disorganization of cerebral cortical architecture in medial parts of the forebrain and normal cortex in lateral parts, including the radial glial fibers. This preserved lateral cortex may explain why some children with holoprosencephaly have better intellectual function than expected and may also be important in the pathogenesis of epilepsy, by contrast with malformations such as lissencephaly, in which the entire cerebral cortex is involved. Epilepsy in some, but not all, cases also may be related to the sequential maturation of axonal terminals in relation to the neurons they innervate. Diabetes insipidus is a complication in a majority of patients; other neuroendocrinopathies occur less frequently. Secondary down regulation of the OTP gene or of downstream genes such as BRN2 or SIM1 may result in failure of terminal differentiation of magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei. Disoriented radial glial fibers or abnormal ependyma may allow aberrant migration of neuroepithelial cells into the ventricle. A new classification of holoprosencephaly is needed to integrate morphologic and genetic criteria. PMID- 11785509 TI - Holoprosencephaly (lobar form) associated with bilateral vocal cord palsy. AB - There have been many causes associated with bilateral vocal cord palsy, both congenital and perinatal. Until now, the main congenital causes of bilateral vocal cord palsy have been associated with meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. We report a patient with bilateral vocal cord palsy associated with the lobar form of holoprosencephaly. In this case, bilateral vocal cord palsy was caused by the disruption of the cortical laryngeal motoneurons. Neonatal stridor must be carefully evaluated by the neonatologist to exclude severe cerebral anomalies. PMID- 11785510 TI - Long-term survival in a child with arthrogryposis multiplex congenita and spinal muscular atrophy. AB - Spinal muscular atrophy type 0 is a severe form of spinal muscular atrophy that is usually fatal in the first months of life. These children present with arthrogryposis multiplex congenita and respiratory compromise. We describe a child with spinal muscular atrophy and arthrogryposis multiplex congenita who has had a much better course and is alive without ventilator support at age 6 years. This case illustrates that the prognosis for spinal muscular atrophy and arthrogryposis multiplex congenita cannot always be predicted with certainty. PMID- 11785511 TI - Attenuation of somatosensory evoked potentials during positioning in a patient undergoing suboccipital craniectomy for Chiari I malformation with syringomyelia. AB - Intraoperative electrophysiologic monitoring can diminish the risk of neurologic injury by enabling the detection of injury at a time when it can be reversed or minimized. This report describes a 14-year-old girl with a Chiari's malformation type I and syringomyelia who underwent a suboccipital decompression and dural patch grafting with concurrent somatosensory evoked potentials. When the patient was turned into the prone position and the neck was flexed, the left-sided somatosensory evoked potential deteriorated. After the patient's neck was repositioned, the left median nerve potential improved but did not return to baseline. Postoperatively, the patient had decreased proprioception of her left arm, which completely resolved at 2-week follow-up. This single case report does not establish the need for routine somatosensory evoked potential monitoring. Nevertheless, deterioration of the potential in this case led directly to a change in the surgical positioning, which may have significantly reduced the chances of a permanent neurologic injury. PMID- 11785513 TI - [48th meeting of the Japanese Society of Clinical Pathology. Yokohama, Japan. August 26-29, 2001. Abstracts]. PMID- 11785512 TI - Roger Alan Brumback, MD, selected as 2001 Alumni Fellow of the Pennsylvania State University College of Medicine. PMID- 11785514 TI - British court orders surgery that will kill one Siamese twin. PMID- 11785515 TI - Couple leave Italy after rebuff over surrogate motherhood. PMID- 11785516 TI - Court says a partner can veto an embryo implantation. PMID- 11785517 TI - 2 babies, 1 heart, 90 minutes for a miracle. PMID- 11785518 TI - New rules on use of human embryos in cell research. PMID- 11785519 TI - How companies stall generics and keep themselves healthy. PMID- 11785520 TI - Behavior modification. PMID- 11785521 TI - Behavioral regulation of the milieu interne in man and rat. AB - In regulating the internal homeostatic environment mammals, by necessity, employ behavioral strategies that differ from the tactics used in coping with contingencies in the external environment. When an animal consumes a meal, the palatability of that meal is automatically adjusted in accordance with the ultimate internal effects of that meal. If the meal causes toxicosis, the animal acquires an aversion for the taste of the meal; conversely, if recuperation follows ingestion of the meal, the taste of that meal is enhanced. Unlike the learning that occurs when externally referred visual and auditory signals are followed by punishment in the form of peripheral pain or reward in the form of food in the mouth, conditioning to the homeostatic effects of food can occur in a single trial and rarely requires more than three to five trials, even though the ultimate effects of the meal are delayed for hours. Paradoxically, the animal need not be aware of the ultimate internal effect in the same sense that it is aware of external contingencies. For example, an aversion can be acquired even if the animal is unconscious when the agent of illness is administered. Thus, the way in which food-effects are stored in memory may be fundamentally different from the way in which memories of specific time-space strategies devised for external contingencies are stored. This separation of function is indicated by limbic lesions which disrupt conditioning to a buzzer that is followed by shock and facilitate conditioning to a taste that is followed by illness. Operationally speaking, one can describe both aversion conditioning and buzzer-shock conditioning in the spacetime associationistic terms of classical conditioning. However, psychologically speaking, one must realize that in aversion conditioning the animal does not act as if it were acquiring an "if-then" strategy. It acts as if a hedonic shift, or a change in the incentive value of the flavor were taking place. Such hedonic shifts are critical in regulation of the internal milieu. When an animal is in need of calories, food tends to be more palatable; as the caloric deficit is restored, food becomes less palatable. If the animal's body temperature is below optimum, a warm stimulus applied to the skin is pleasant. When body temperature is too high, the converse is true. In this way, homeostatic states monitored by internal receptors produce changes in the incentive values of external stimuli sensed by the peripheral receptors, and guide feeding behavior. In mammals at least, the gustatory system, which provides sensory control of feeding, sends fibers to the nucleus solitarius. This brainstem relay station also receives fibers from the viscera and the internal monitors of the area postrema. Ascending fibers bifurcate at the level of the pons and project toward the feeding areas of the hypothalamus and the cortex. The olfactory system which primarily projects to the limbic system does not play a primary role in adjusting food incentives. Rather, it plays a secondary role in the activation of feeding, as do other external sensory systems. This specialized conditioning mechanism, which specifically adjusts gustatory hedonic values through delayed visceral feedback, is widespread among animals, including man and rat. These two species are remarkably similar in their thresholds and preferences for gustatory stimuli. The behavioral similarities are based on the animals' having similar gustatory systems, similar convergence of gustatory and internal afferents to the nucleus solitarius, and similar midbrain regulatory mechanisms. Thus, it is not surprising that the feeding of obese rats with internal hypothalamic damage resembles the feeding of obese human beings insensitive to the internal signs of this caloric state. Obviously, man has a highly specialized form of symbolic communication and the rat does not, yet man's cognitive specialization does not prevent him from developing aversions to food consumed before illness even when he knows that his illness was not caused by food (43). PMID- 11785522 TI - Teratogens and the Delaney Clause. PMID- 11785523 TI - Dalkon shield affair: a bad lesson in science and decision-making. PMID- 11785524 TI - Language in man, monkeys, and machines. PMID- 11785525 TI - Accreditation of human research participant protection programs. PMID- 11785526 TI - New federal rule on protecting children as research subjects. PMID- 11785527 TI - Subject's representative says researcher changed his report after problem arose. PMID- 11785528 TI - No constitutional protection for individual researcher's reputation. PMID- 11785529 TI - Prisoner number 284797. PMID- 11785530 TI - Not making the genetic cut. PMID- 11785534 TI - A father's trial and the case for personhood. PMID- 11785535 TI - Amyloplast distribution in hairy roots induced by infection with Agrobacterium rhizogenes. AB - To elucidate the rapid and plagiotropic growth of hairy root induced by A. rhizogenes, a root apex was investigated with respect to it's amyloplast deposition, activity of alpha-amylase and glucose content. The amyloplasts distributed in the hairy roots were fewer than those of the adventitious root. Since auxin availability is enhanced in hairy roots, it could affect the statolith degradation by elevating alpha-amylase activity so that the energy requirement for rapid growth could be fulfilled as represented of glucose content. Consequently, it is suggested the overall decrease of starch grains could result in the lack of gravi-response in hairy roots. PMID- 11785536 TI - Mini ecosystem in space--preliminary experiment on board STS-77. AB - An enclosed ecosystem which is stable on Earth will behave differently when brought into space. Micro-gravity and radiation will affect the dynamics of material circulation or the activities of small creatures of the ecosystem. One series of space experiments aiming to address such issues was planned in the United States (It is termed as ABS--Autonomous Biological System) and Japanese group has been involved with cooperating with the analysis of the flight samples. Before the ecosystem will be on board Russian Space Station "Mir" later 1996 for 3 months, a preliminary flight was carried out in May 1996 on Space Shuttle (STS 77) for 10 days flight. It was the first of such experiments to fly one whole ecosystem in space. PMID- 11785537 TI - [Responses of ankle plantar-flexors to various inhibitions of muscular activities in rats]. AB - Effects of hindlimb suspension, tenotomy, denervation, and/or the combination of these models on plantar-flexors were studied in adult rats. Suspension-induced atrophy was not promoted by addition of tenotomy. But the magnitude of the atrophy was advanced if denervation or both denervation and tenotomy were combined with 5-day hindlimb suspension. Similar effects were noted in the cross sectional area of single muscle fibers, especially of slow-twitch fibers. A shift of muscle fiber type from slow- to fast-twitch type was also induced mainly in soleus. The atrophy and fiber transformation were closely associated with a passive shortening of muscle due to the plantar-flexion of ankle and/or tenotomy and a disappeared electrical activity caused by denervation. The fiber atrophy, but not the shift of fiber type, was further advanced by the combination of tenotomy and denervation. It is suggested that muscle atrophy is caused by the decreased fiber size and protein content. The water content was also reduced proportionally. PMID- 11785538 TI - Recovery of Deinococcus radiodurans from radiation damage was enhanced under microgravity. AB - Effect of microgravity on recovery of bacterial cells from radiation damage was examined on the IML-2 mission in 1994 using extremely radioresistant bacterium Deinococcus radiodurans. The cells were lyophilized and exposed to 60Co gamma rays with doses 2 to 12 kGy before the space flight. At the end of the mission, the cells were mixed on board with liquid nutrient medium to allow the cells to start recovery process from the radiation damage. Afterwards the cells were stored at 4 degrees C until landing. The influence of cosmic radiation was negligible, because total absorbed dose of space radiation measured during the mission was less than 2 mGy and this bacterium does not decrease its viability after both gamma-rays and high-LET heavy charged particles irradiation with doses up to 5 kGy. The survival of the cells incubated in space increased significantly compared with the ground controls, suggesting that the recovery of this bacterium from radiation damage was enhanced under microgravity. PMID- 11785539 TI - Harming and benefiting the dead. AB - The traditional view of grief resolution requires the bereaved person to disengage from the deceased. This is often expressed as a necessary "letting go" of the past for the survivor to be free to continue her or his life and form new relationships. Contemporary grief theory, in contrast, recognizes that healthy grieving involves maintaining bonds with the deceased. The relationship between the bereaved person and the person who has died, although transformed, is ongoing. This article takes as its focus one aspect of the continuing relationship between the living and the dead. It begins with the noncontroversial claim that some actions that involve the dead are wrong from an ethical perspective. What is controversial is the explanation of the wrongness of these actions. It is argued that the dead can be harmed by having their interests thwarted and, conversely, they can be benefited by having their interests promoted. Posthumous harm and benefit are possible because people who are now dead possessed interests prior to death that continue to exert a claim after death. PMID- 11785540 TI - International comparison of studies using the perinatal grief scale: a decade of research on pregnancy loss. AB - The Perinatal Grief Scale (PGS) has been used in many studies of loss in pregnancy, including miscarriage, stillbirth, induced abortion, neonatal death, and relinquishment for adoption. This article describes 22 studies from 4 countries that used the PGS with a total of 2485 participants. Studies that report Cronbach's alpha for their own samples give evidence of very high internal consistency reliability. Evidence for the validity of the PGS is also reviewed, such as convergent validity seen in its association with measures of mental health, social support, and marital satisfaction. The standard errors of the means for the total scale and for the subscales reveal fairly consistent scores, in spite of very different samples and types of loss; computation of means and standard deviations for the studies as a whole permits us to establish normal score ranges. Significantly higher scores were found in studies that recruited participants from support groups and self-selected populations rather than from medical sources, and from U.S. studies compared with those in Europe. PMID- 11785541 TI - Near-death experiences with reports of meeting deceased people. AB - Few scientists have taken seriously the interpretation of near-death experiences (NDEs) as evidence for survival after death, even though most people having such an experience have become convinced that they will survive death and several features of NDEs are at least suggestive of survival. This article compares survival and some nonsurvival interpretations of NDEs in light of one feature suggestive of survival, that of reports of having seen deceased persons during the NDE. Several features of 74 NDEs involving such reports were compared with those of 200 NDEs not involving such reports. Although some of the findings could support either a survival or a nonsurvival interpretation, several other findings may weaken the primary nonsurvival hypothesis, that of expectation. Additionally, the convergence of several features suggesting survival and the convergence of features that require multiple kinds of alternative explanations, in individual cases as well as in large groups of cases, warrant our considering the survival hypothesis of NDEs more seriously than most scientists currently do. PMID- 11785542 TI - Economic influences on end-of-life care: empirical evidence and ethical speculation. AB - Although very little actual evidence on the issue is available, much ethical speculation has been voiced about the probable impact of the current cost containment-oriented economic climate in the United States on decisions that are being made and implemented in the context of end-of-life medical care. This article, after noting that numerous factors besides money drive the behavior of various actors in the health care system, turns to the economic influences on care for dying patients. These influences, both real and imagined, may be manifested in the amount of de facto health care rationing by age that occurs, the prevalent fears of older persons regarding both overtreatment and undertreament, the financial expectations as well as disappointments emanating from the practice of advance medical planning, and the paucity of options from which many impoverished individuals must choose at the end of their lives. It is too early to judge specifically the impact of managed care on end-of-life decisions, but positive opportunities as well as perils may materialize. PMID- 11785543 TI - Is training in psychology associated with increased responsiveness to suicidality? AB - Training is associated with improved responses to suicidal individuals, but it is not clear whether any training helps or whether the training needs to be in psychology. The authors compared beginning and advanced psychology graduate students and practicing psychologists to nursing graduate students. A total of 139 participants in these 4 groups read a vignette about Pat, who had either contemplated suicide or never contemplated suicide, then completed questions about how they would respond to a distressed telephone call from Pat, how suicidal they thought Pat was, and how good a no-suicide contract would be for Pat. Advanced students and psychologists were more helpful in their responses than beginning graduate students, who were more helpful than nursing graduate students. However, all participants noticed whether Pat had contemplated suicide, and all were faintly positive about no-suicide contracts. PMID- 11785544 TI - Health equity and social justice. AB - There is consistent and strong empirical evidence for social inequalities in health, as a vast and growing literature shows. In recent years, these findings have helped to move health equity high on international research and policy agendas. This paper examines how the empirical identification of social inequalities in health relates to a normative judgment about health inequities and puts forward an approach which embeds the pursuit of health equity within the general pursuit of social justice. It defends an indirect approach to health equity, which views social inequalities in health as unjust in so far as they are the result of an unjust basic structure of society in Rawls' sense. PMID- 11785545 TI - Postmenopausal women and the right of access to oocyte donation. AB - This paper raises the question of distributive justice in the allocation of donor oocytes. The shortage of oocytes has resulted in waiting lists of several years. The largest group of candidate recipients are postmenopausal women. Questions have been raised about their right to these scarce resources. The criteria that might be morally relevant in the allocation decision are divided according to the stage at which they are applied: either for the admission to the waiting list or for the ranking of those already on the waiting list. Five factors are analysed: success rates, fault, parental competence, medical urgency and waiting time. It is concluded that none of the relevant criteria justifies discrimination against postmenopausal women. PMID- 11785546 TI - Nancy B and Nancy F. AB - In this article I provide a virtuous slippery slope argument which shows that there is no morally significant difference between passive and active euthanasia. At the top of the slope is an example of passive euthanasia; at the bottom, an example of active euthanasia. For each pair of cases down the slope there is nothing that sensibly makes a morally significant difference between the pair of cases. Thus, there is no morally significant difference between passive euthanasia and active euthanasia. PMID- 11785547 TI - Health care ethics. PMID- 11785548 TI - Physicians' voices on physician-assisted suicide: looking beyond the numbers. AB - Most empirical research examining physician views on physician-assisted suicide (PAS) has used quantitative methods to characterize positions and identify predictors of individual attitudes. This approach has generated limited information about the nature and depth of sentiments among physicians most impassioned about PAS. This study reports qualitative data provided by 909 physicians as part of a larger survey (N = 2,805) regarding attitudes toward and experiences with PAS and palliative care. Emergent themes illustrate important clinical, social, and ethical considerations in this area. The data illustrate the diverse and ardent responses that PAS evokes among certain physicians. The role of physicians' personal values is central to discussions about legalization of PAS. Polarized views such as those expressed by physicians in this study are not likely to be reconciled, thereby constraining the development of public policy regarding PAS. PMID- 11785550 TI - Death as a human passage: compassionate care for persons dying in critical care units. PMID- 11785549 TI - Perceptions of confidentiality violations among psychologists. AB - This study explored psychologists' perceptions of confidentiality violations. One hundred ninety-five psychologists answered questionnaires about a vignette regarding a male therapist accused of violating the confidentiality of a female client. The vignette varied on the following variables: (a) Confidential information was conveyed to either an insurance company or another client, (b) the therapist's account of the violation included either an excuse or a justification, and (c) scapegoating was included or not included in the account. The insurance condition and excuse condition produced more lenient judgements of the violations. However, excuses elicited more negative judgments of the therapist. Scapegoating generally elicited more negative judgments. Differences in the recipient of confidential information and the accounts given for violations have an impact on psychologists' perceptions of confidentiality violations. PMID- 11785551 TI - Why aren't nurses clamoring for intensivists? PMID- 11785552 TI - Integrating nonpharmacological, adjunctive interventions into critical care practice: a means to humanize care? PMID- 11785553 TI - Early socialization of new critical care nurses. AB - BACKGROUND: Critical care nurses provide care to acutely ill patients, yet little is known about the early socialization processes of new nurses to critical care units from the nurses' perspectives. OBJECTIVES: To explore the early socialization processes of critical care nurses. METHODS: A grounded theory design was used to generate a local theory of how critical care nurses experience socialization. Interviews and journals of participants (N = 10) during the first 4 to 5 months of the socialization experiences were collected. Preceptors were interviewed to triangulate data. Orientation materials and field notes were examined. RESULTS: A process of 5 phases was uncovered: the prodrome, welcome to the unit, disengagement/testing, on my own, and reconciliation. Participants experienced difficulty while being evaluated by preceptors early in the orientation process because of changing expectations. Participants also expressed disappointment in their level of comfort at the end of the orientation. The theory termed "navigating the challenge" explains the nature of the changing expectations that new critical care nurses face during their socialization process. CONCLUSIONS: This exploratory study defines the phases that new critical care nurses experience during the early socialization process. Phase-specific recommendations are made on the basis of the results of the study. PMID- 11785554 TI - Tobacco dependence curricula in acute care nurse practitioner education. AB - BACKGROUND: Tobacco dependence is the leading preventable cause of death in the United States, yet healthcare professionals are not adequately educated on how to help patients break the deadly cycle of tobacco dependence. OBJECTIVE: To assess the content and extent of tobacco education in the curricula of acute care nurse practitioner programs in the United States. METHODS: A survey with 13 multiple choice items was distributed to the coordinators of 72 acute care nurse practitioner programs. The survey was replicated and modifiedfrom previous research on tobacco dependence curricula in undergraduate medical education. RESULTS: Fifty programs (83%) responded to the survey. Overall, during an entire course of study, 70% of the respondents reported that only between 1 and 3 hours of content on tobacco dependence was covered. Seventy-eight percent reported that students were not required to teach smoking-cessation techniques to patients, and 94% did not provide opportunities for students to be certified as smoking cessation counselors. Sixty percent reported that the national guidelines for smoking cessation were not used as a curriculum reference for tobacco content. CONCLUSIONS: The majority of acute care nurse practitioner programs include brief tobacco education. More in-depth coverage is required to reduce tobacco dependence. Acute care nurse practitioners are in a prime position to intervene with tobacco dependence, especially when patients are recovering from life threatening events. National recommendations for core tobacco curricula and inclusion of tobacco questions on board examinations should be developed and implemented. PMID- 11785555 TI - Nurses' accuracy in estimating backrest elevation. AB - BACKGROUND: Positioning patients is a key component of nursing care and can affect their morbidity and mortality. The Centers for Disease Control and Prevention recommend that patients receiving mechanical ventilation have the head of the bed elevated 30 degrees to 45 degrees to prevent nosocomial pneumonia. However, use of higher backrest positions for critically ill patients is not common nursing practice. Backrest elevation may be affected by the accuracy of nurses' estimates of patients' positions. OBJECTIVES: To determine the difference between nurses' estimates of bed angles and measured bed angles and to describe the relationship between nurses' characteristics and the accuracy of their estimates. METHODS: A convenience sample of 67 nurses attending the 1999 American Association of Critical-Care Nurses National Teaching Institute and Critical Care Exposition in New Orleans, La. Each subject provided demographic information and estimated 3 bed angles. The angles were preselected by using a random number table. Summary statistics were used and were categorized according to the demographic information provided by participants. Estimated angles were correlated with measured angles, and accuracies in estimating angles were correlated with demographic characteristics. RESULTS: Nurses were accurate in estimating bed angles (correlation, 0.8488). Demographic information, including sex, age, years of practice, years of critical care practice, basic education, highest educational level, and present position had no relationship to accuracy. CONCLUSIONS: Nurses are able to estimate backrest elevation accurately. Other explanations are needed to understand why recommendations for backrest elevation are not used in practice. PMID- 11785556 TI - Monitoring urinary bladder temperature in the intensive care unit: state of the science. AB - Body temperature of patients in critical care units can be monitored with a variety of devices and at a variety of body sites. In recent years, monitoring of urinary bladder temperature has become more common. Temperature-sensing indwelling urinary catheters allow continuous drainage of urine and continuous measurement of body temperature. This article provides a comprehensive and critical review of research undertaken in intensive care units to compare body temperatures measured in the urinary bladder with temperatures measured at a core site, the pulmonary artery. The studies support the use of urinary bladder temperature as a reliable index of core temperature during times of thermal stability. For critically ill patients who are already under considerable stress and whose condition necessitates the use of an indwelling urinary catheter, bladder temperature monitoring is an easy and convenient method that eliminates the need to use alternative sites. Further studies on the effects of shivering and urinary flow rate on temperatures measured in the bladder in critical care patients are needed. The economics of monitoring urinary bladder temperature also should be studied. PMID- 11785557 TI - Electrocardiographic abnormalities in patients with subarachnoid hemorrhage. AB - Subarachnoid hemorrhage is a serious neurological disorder that is often complicated by the occurrence of electrocardiographic abnormalities unexplained by preexisting cardiac conditions. These morphological waveform changes and arrhythmias often are unrecognized or misinterpreted, potentially placing patients at risk for inappropriate management. Many previous investigations were retrospective and relied on data collected in an unsystematic manner. More recent studies that included use of serial electrocardiograms and Holter recordings have provided new insight into the high prevalence of electrocardiographic changes in subarachnoid hemorrhage. Research on the prevalence, duration, and clinical significance of these electrocardiographic abnormalities and on associated factors and etiological theories is reviewed. PMID- 11785558 TI - Effect of positioning on oxygenation in single-lung transplant recipients. AB - BACKGROUND: Many benefits and adverse effects of positioning are related to changes in ventilation and perfusion. A number of unique factors related to the allograft make the effects of positioning difficult to determine in single-lung transplant recipients. OBJECTIVES: To determine the effect of 3 body positions (supine, lateral with allograft lung down, and lateral with native lung down) on oxygenation and blood flow in single-lung transplant recipients in the 24 hours immediately after surgery. METHODS: A quasi-experimental repeated-measures design with stratified assignment to 1 of 3 different sequencing patterns for turning group was used to study 15 transplant recipients, 9 with emphysema and 6 with fibrosis. Oxygenation, ventilation, and blood flow measures (heart rate, blood pressure) were assessed after each turn. The effect of ischemic reperfusion injury was also explored. RESULTS: The oxygenation, ventilation, and bloodflow variables did not differ significantly across group, diagnosis, or time. Oxygenation variables measured when the allograft lung was dependent did not differ significantly from such measurements obtained when the native lung was dependent. CONCLUSIONS: No single position maximizes oxygenation in the immediate postoperative period in single-lung transplant recipients. Although a single standard protocol for positioning cannot be supported, the study does support the idea that transplant recipients can be safely turned in the immediate postoperative period without compromising oxygenation or hemodynamic status. PMID- 11785559 TI - Apocalypse when? PMID- 11785560 TI - Ethics, ethical comportment, and etiquette. PMID- 11785561 TI - Focus: hypertension in the aged population. AB - The treatment of the elderly hypertensive patients has reduced the incidence of strokes, cardiovascular events, and cardiovascular morbidity. Regrettably, few hypertensive patients over 80 years of age are being treated, and those who are, are not being treated effectively. Hypertension, at any age, should be treated with a goal of BP <140/90 mmHg, as set by the Joint National Committee on Hypertension. This message should be spread throughout the medical community. PMID- 11785562 TI - ST-elevation myocardial infarction. PMID- 11785563 TI - A time for change. PMID- 11785564 TI - Temporal variations in school-associated student homicide and suicide events- United States, 1992-1999. AB - Recent, widely reported violent deaths associated with schools have led many adults to believe that a school shooting could occur in their community and many children to express increasing concern about their own safety at school. CDC, in collaboration with the U.S. Education and Justice departments, has been tracking school-associated violent deaths since the 1992-1993 school year. To evaluate whether the risk for school-associated violent death varies during the school year, CDC analyzed monthly counts of school-associated homicide and suicide events that occurred among students in elementary and secondary (middle, junior high, and senior high) schools in the United States. This report summarizes the results of these analyses, which indicate that student homicide event rates are usually highest near the start of the fall and spring semesters, and suicide event rates are highest during the spring semester. These findings can assist school personnel in planning and implementing violence-prevention programs. PMID- 11785565 TI - Effectiveness of a middle school vaccination law--California, 1999-2001. AB - In 1996, the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Association of Family Physicians, and the American Medical Association recommended a routine health-care visit for adolescents aged 11-12 years. During this visit, adolescents not fully vaccinated should receive up to four recommended vaccines (hepatitis B, a measles-containing vaccine [MCV], varicella, and tetanus-diphtheria) and other preventive services and counseling. Because many adolescents are not up-to-date for all of these vaccines, 43 states have developed middle school entrance requirements or laws for one or more of these vaccines. Since 1997, CDC, in collaboration with the Pre-Teen Health Project in San Diego, California, has evaluated the impact of the state's middle school vaccination law, which requires students entering seventh grade on or after July 1, 1999, to have documented receipt of three doses of hepatitis B and two doses of MCV or to have obtained a written exemption based on personal beliefs or medical grounds. This report summarizes the results of that analysis, which indicate that when school entrance requirements are enforced, high vaccination coverage can be achieved. PMID- 11785566 TI - Effectiveness of school-based programs as a component of a statewide tobacco control initiative--Oregon, 1999-2000. AB - With funds available from revenue generated by a voter-initiated ballot measure to increase the state cigarette excise tax, the Oregon Health Division (OHD) created the Tobacco Prevention and Education Program (TPEP) in 1997. Coalitions in all Oregon counties, a countermarketing campaign, a statewide tobacco cessation quitters' helpline, and competitive grants to community groups, tribal associations, and school districts are supported by TPEP; 12% of TPEP's $8.5 million annual funding was used to implement CDC's Guidelines for School Health Programs to Prevent Tobacco Use and Addiction in 23 school districts or consortia of districts. Data from annual school-based surveys conducted to monitor adolescent risk behavior indicated that from 1999 to 2000, 30-day smoking prevalence among eighth grade students declined more in funded schools than in a comparison group of nonfunded schools. The declines were significantly greater among schools with high and medium levels of implementation. These results suggest that comprehensive school-based programs can be an effective component of statewide antitobacco efforts. PMID- 11785567 TI - Human anthrax associated with an epizootic among livestock--North Dakota, 2000. AB - On August 28, 2000, the North Dakota Department of Health was notified by a local clinician of a patient with a cutaneous lesion suggestive of anthrax following exposure to an infected animal carcass. This report summarizes the investigation of this case, which was associated with an anthrax epizootic among livestock in North Dakota, and emphasizes the importance of increased vigilance for human cases of anthrax during and following outbreaks of anthrax among livestock. PMID- 11785568 TI - Botulism outbreak associated with eating fermented food--Alaska, 2001. AB - On January 18, 2001, the Alaska Division of Public Health was informed by a local physician of a possible botulism outbreak in a southwest Alaska village. This report summarizes the findings of the outbreak investigation, which linked disease to eating fermented food, and describes a new botulism prevention program in Alaska. PMID- 11785569 TI - Self-reported asthma prevalence among adults--United States, 2000. AB - Asthma is a chronic inflammatory disorder of the airways characterized by episodes of wheezing, shortness of breath, chest tightness, and cough and is among the most common chronic diseases in the United States, affecting approximately 10.2 million adults during 1996. Direct and indirect costs associated with asthma during 1998 were an estimated $12.7 billion. Despite the prevalence and associated costs of asthma, state-specific data have not been available. This report summarizes state asthma prevalence data collected from the 2000 Behavioral Risk Factor Surveillance System (BRFSS) survey, which indicated that approximately 7.2% of adults residing in the United States reported having asthma. This is the first state-specific asthma prevalence data available for all 50 states. Continued use of the BRFSS asthma questions will allow state health departments to monitor trends in asthma prevalence and to provide data to direct asthma management. PMID- 11785570 TI - Shigellosis outbreak associated with an unchlorinated fill-and-drain wading pool- Iowa, 2001. AB - On June 15, 2001, local physicians reported 11 cases of diarrhea to a county health department. Stool samples from two of these persons were culture confirmed as Shigella sonnei, one person was hospitalized. A preliminary investigation found that nine of these persons recently had visited a large city park with a wading pool. The Iowa Department of Public Health was asked to assist in an investigation of this outbreak. This report summarizes the results of the investigation, which implicated the inadequately disinfected wading pool as the source of the outbreak and presents strategies for preventing such outbreaks. PMID- 11785571 TI - Resistance of Streptococcus pneumoniae to fluoroquinolones--United States, 1995 1999. AB - Streptococcus pneumoniae is the leading cause of community-acquired pneumonia, meningitis, and otitis media in the United States. Because of the emergence of antimicrobial resistance in pneumococci, fluoroquinolones are now recommended by some groups for the treatment of pneumonia in adults, especially when antimicrobial resistance is suspected. Older fluoroquinolones with some antimicrobial activity against the pneumococcus include ciprofloxacin and ofloxacin. Newer fluoroquinolones with higher in vitro activity against the pneumococcus, including levofloxacin, grepafloxacin, gatifloxacin, and moxifloxacin, are available in the United States. Fluoroquinolone resistance to the pneumococcus is rare but may be increasing in Canada. To determine trends of pneumococcal resistance to fluoroquinolones in the United States, invasive pneumococcal disease surveillance data were analyzed from Active Bacterial Core Surveillance (ABCs) during 1995-1999. Fluoroquinolone prescription data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) during 1993-1998. This report summarizes the results of that analysis, which indicate that pneumococci with reduced susceptibility to fluoroquinolones are appearing in the United States. Appropriate use of antibiotics and continuous prospective surveillance for antimicrobial resistance are necessary to slow the emergence of fluoroquinolone-resistant pneumococci. PMID- 11785573 TI - FDA approval for a combined hepatitis A and B vaccine. AB - On May 11, 2001, the Food and Drug Administration (FDA) licensed a combined hepatitis A and B vaccine (Twinrix) for use in persons aged > or = 18 years. Twinrix is manufactured and distributed by GlaxoSmithKline Biologicals (Rixensart, Belgium), and is made of the antigenic components used in Havrix and Engerix-B (GlaxoSmithKline). The antigenic components in Twinrix have been used routinely in separate single antigen vaccines in the United States since 1995 and 1989 as hepatitis A and B vaccines, respectively. PMID- 11785574 TI - Family-centered maternity care in the new millennium: is it real or is it imagined? AB - Family-centered maternity care (FCMC) has become a familiar phrase in today's maternity services; however, the actual implementation in many hospitals is likely to be more "staff-centered" than "family-centered." This article gives an overview of the historical development of family-centered care and the importance of this model of care to a new or growing family's ability to adapt to the stress of birth and parenting. The current status of FCMC is reviewed in relation to prenatal education, intrapartum care, mother-baby nursing, and family visitation. Many lessons have been learned about implementing FCMC over the past 20 years. Suggestions are provided regarding the development of a vision and mission, the institutional culture, systems and clinical management, staff attitudes, and involvement of families. PMID- 11785575 TI - Back to the future: trusting birth. AB - Research over the past 30 years provides support for once again trusting birth. This is a paradigm shift in thinking about birth and requires a dramatic change in the practice of nursing. Confidence in a woman's ability to give birth, the freedom to find comfort in response to pain, and the support of family, friends, and professionals facilitate normal, natural birth. Hospital policies and routine care practices that decrease confidence, restrict freedom and support, and separate mothers from their infants sabotage natural birth and breastfeeding. The goal of the perinatal nurse is to promote, protect, and support women's efforts to give birth naturally and breastfeed their children. PMID- 11785576 TI - The case against elective cesarean section. AB - Prominent American and British obstetricians have been advocating for performing more Cesareans. They argue that Cesarean section is as safe or nearly as safe as vaginal birth, eliminates pelvic floor damage and the consequent symptoms caused by vaginal birth, is safer for the infant, and is desired by many women; however, abundant evidence in the medical literature refutes the validity of those claims. PMID- 11785577 TI - Vigilant watching over: mothers' actions to safeguard their premature babies in the newborn intensive care nursery. AB - The critical ethnography described in this article explored how a diverse group of 12 mothers describe and interpret their experience of having a hospitalized premature baby, including the mothers' actions in a newborn intensive care unit (NICU) and conditions affecting their descriptions, interpretations, and actions throughout 448 hours of participant observation. A central feature of their experience encompassed a repertoire of actions to vigilantly watch over their babies in the NICU. The results of this study suggest that health care providers often interpreted mothers' actions differently than intended, which creates barriers to achieving family-centered care in the NICU. PMID- 11785578 TI - Implementing developmentally supportive family-centered care in the newborn intensive care unit as a quality improvement initiative. AB - Intensive care nursery personnel increasingly seek to practice developmental and family-centered care, but become frustrated when attempting implementation. Reports of effective change strategies for integration to practice are limited. This article presents a summary of one unit's experience using the performance improvement process to move toward a developmentally supportive, family-centered care delivery model. Results to date indicate that a comprehensive quality improvement process guided by a unit-based newborn developmental specialist can provide the framework to achieve the change from traditional, provider-centered, task-directed care to holistic, individualized, relationship-based care. PMID- 11785579 TI - Building relationships with families in the NICU: exploring the guarded alliance. AB - Extremely low-birthweight infants and their families experience prolonged hospitalization in the newborn intensive care unit (NICU). Prolonged hospitalization is particularly stressful for the family, leading to distress in most aspects of their lives, including separation of parents from each other and from other family members, a need for increased psychological support, and increased economic concerns. Based on these characteristics, these families appear to have needs more similar to that of families caring for chronically ill members. Indeed, this initial hospitalization may be the prelude to coping and surviving with a chronic illness for many of these children and families. This article proposes the adaption of "guarded alliance" as a framework for developing relationships and providing care to families in the NICU. This framework was derived from research with families of the chronically ill. Supportive research is used to justify the adoption of this framework for interactions with families in the NICU. In addition, linkages to family-centered care principles in critical care settings are also discussed. PMID- 11785580 TI - Sensitivity and specificity of a computerized test of attention in the diagnosis of Attention-Deficit/Hyperactivity Disorder. AB - Attention-Deficit/Hyperactivity Disorder (ADHD) is difficult to diagnose due to the subjectivity of its symptoms and lack of specific assessment measures. Computerized tests of attention have recently been used as objective measures that may assist in the diagnosis of the disorder. The present study evaluated consistency between the Conners Parent Rating Scale and the Test of Variables of Attention (TOVA), which is a computerized test of attention designed to identify symptoms associated with ADHD, in children clinically diagnosed with ADHD (n = 28) and controls (n = 20). Our results showed that both the Conners and the TOVA indicated significant problem areas suggestive of an attention deficit in approximately 85% of children who were clinically diagnosed with ADHD. However, the TOVA also found attentional problems in approximately 30% of control children, whereas none of the controls scored abnormally on the Conners. As computerized measures are administered more frequently, there may be a risk of overdiagnosis and treatment of "ADHD" in normal children. A combined approach using questionnaires, clinical evaluation, and computerized tests of attention in the assessment of possible ADHD may provide the most accurate means of diagnosis. PMID- 11785582 TI - Assessing depression in Russian psychiatric patients: validity of MMPI and Rorschach. AB - We tested the criterion, concurrent, and content validity of depression indicators in 180 Russian psychiatric patients. Indicators from the Exner Rorschach (DEPI, CDI) and the Russian MMPI (Berezin Scale 2, Wiggins depression content) were compared to Hamilton (HRSD) scores and 3 types of diagnosis: traditional Russian, contemporary Western (ICD-10), and a mixed version. The MMPI scales had significant associations with each other and each criterion. The Rorschach indexes were unrelated to all other variables, even when their affective, cognitive, and interpersonal components were analyzed separately, response styles were taken into account, or the 2 indexes were used in combination. Nevertheless, sample means on 107 variables were roughly similar to Exner's norms. The study represents an initial step towards establishing the validity of instruments commonly used in Russia and North America for assessing depression among Russians. PMID- 11785583 TI - Reliability generalization: exploring reliability variations on MMPI/MMPI-2 validity scale scores. AB - The study utilized the measurement meta-analytic method called "reliability generalization" to examine (a) the typical reliability, (b) the variability of score reliability, and (c) the factors predicting variability of score reliability on the three MMPI validity scales. Across studies the reliability coefficients on the three validity scales ranged from .16 to .93, with the F scale having the most variability, as might be expected. Regression analyses suggested that the age of participant best predicted the variation of reliability coefficients. PMID- 11785581 TI - Cross-validation of prediction equations for Wechsler Memory Scale-III Indexes. AB - Six prediction equations were previously found to predict to Wechsler Memory Scale-III (WMS-3) Immediate Memory Index (IM) and General Memory Index (GM) using two- or three-subtest combinations. The equations were cross-validated on a sample of 214 mixed clinical patients from an entirely different location in the Midwest. The two three-subtest prediction equations (including Logical Memory, Verbal Paired Associates, and either Faces or Family Pictures) better estimated IM and GM than did the two-subtest equations (Logical Memory and Verbal Paired Associates). Correlations for the former equations correlated .97 and .96 with full WMS-3 IM and GM, respectively. In addition, at least 95% of the predicted scores were within two SEMs of obtained IM and GM scores. The two-subtest equations correlated only .89 for IM and .92 for GM. The predicted scores that fell within two SEMs captured 78% and 88% of the cases for IM and GM, respectively. The results provide support for the use of the three-subtest prorated forms of the WMS-3 to estimate IM and GM. PMID- 11785584 TI - Estrogen replacement therapy: a perspective on cognitive impact. AB - Studies suggest that use of estrogen replacement therapy (ERT) after menopause may be beneficial toward preservation of cognitive functioning. However, potentially confounding variables such as alcohol consumption are typically not systematically considered. The purpose of this study was to determine whether ERT users and nonusers differ with regard to memory and concentration ability when potential confounds are eliminated. Alcohol consumption was included as an independent variable so that ERT by alcohol interactions could be examined. One hundred-sixty-two postmenopausal women participated in the study and were classified as moderate drinkers or teetotalers. Logical Memory (Wechsler Memory Scale-Revised), Digit Span (Wechsler Adult Intelligence Scale-Revised) and the Cognitive Symptom Checklist-Memory subscale were administered. No main effects of ERT were found. However, ERT by alcohol interactions among some Digit Span Forward variables were observed. We conclude that confounding variables such as alcohol consumption, may be at least partly responsible for observed differences in cognition commonly attributed to ERT. PMID- 11785585 TI - A measure of the stability of family activities: an initial examination. AB - The Stability of Activities in the Family Environment (SAFE) was designed to sample activities that could occur with some degree of regularity and stability in a variety of families. The SAFE was found to have adequate internal consistency and its validity was suggested by its relationship to other measures of family functioning and to measures of adjustment. The results of the present investigation are consistent with the differentiation of two domains of stability of family activities; those that occur on a daily basis, primarily within the home, and those that are more social in nature and might occur outside of the home. The present findings also indicate the potential value of further consideration of the roles of overall stability of family activities and also of stable positive family activities in facilitating adaptive development. PMID- 11785586 TI - MMPI-2 scale F(p) and symptom feigning: scale refinement. AB - The F(p) scale of the MMPI-2 is widely used to help identify exaggeration of psychological problems in psychiatric, forensic, and neuropsychological settings. The scale was constructed by selecting all MMPI-2 items (N = 27) that were endorsed by less than 20% of a sample of VA psychiatric inpatients and 20% of the normative sample used in restandardizing the MMPI-2. Although F(p) is used to measure symptom exaggeration and malingering, 4 of its 27 items load on the Lie (L) scale, which is known to be a measure of defensiveness and symptom underreporting. These four items, which express a denial of occasional anger, irritability, and procrastination, could conceivably measure an uncommon expression of defensiveness. This study used 150 neuropsychological referrals to test the hypotheses that (a) the four L scale items measure defensiveness, not exaggeration, and (b) the elimination of these items improves the utility of F(p) in assessing symptom exaggeration. The results indicate that the four L scale items are associated with defensiveness, not with symptom exaggeration. One third of the patients had an average T-score artifact of 9.5 points on F(p) as a result of endorsing these L scale items, with a range of 0T to 21T. Using the K scale as a criterion for level of problem disclosure, a shortened version of F(p) (omitting the four L scale items) was superior to F(p) as a measure of symptom exaggeration (r = -.46 vs. -.36, r2 = 21% vs. 13% of the variance). The implications for clinical practice are discussed. PMID- 11785587 TI - Psychometric study of a brief screen for PTSD: assessing the impact of multiple traumatic events. AB - Most measures of posttraumatic stress disorder (PTSD) symptoms are limited in that they focus on a single traumatic event and cannot be used to assess symptoms in persons who report no traumatic events. The utility of the brief PTSD measures that do not key to a single trauma is limited by lengthiness and high reading levels. The Screen for Posttraumatic Stress Symptoms (SPTSS) is a brief, self report screening instrument for PTSD symptoms that overcomes these limitations by assessing PTSD symptoms using a low reading level and without keying them to a specific traumatic event. In a sample of 136 psychiatric inpatients, the SPTSS showed good internal consistency, a high sensitivity rate, and a moderate specificity rate. The concurrent and construct validity of the SPTSS were supported by strong correlations with symptom and trauma experience measures and by comparisons of SPTSS scores of groups with different trauma histories. PMID- 11785588 TI - The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with clinical and nonclinical samples. AB - Past suicidal behaviors including ideation and attempts have been identified as significant risk factors for subsequent suicidal behavior. However, inadequate attention has been given to the development or validation of measures of past suicidal behavior. The present study examined the reliability and validity of a brief self-report measure of past suicidal behavior, the Suicidal Behaviors Questionnaire-Revised (SBQ-R). Participants included psychiatric inpatient adolescents, high school students, psychiatric inpatient adults, and undergraduates. Logistic regression analyses provided empirical support for the usefulness of the SBQ-R as a risk measure of suicide to differentiate between suicide-risk and nonsuicidal study participants. Receiver operating characteristic (ROC) analyses indicated that the most useful cutoff scores on the SBQ-R were 7 for nonsuicidal samples, and 8 for clinical samples. Both the single SBQ-R Item 1 and SBQ-R total scores are recommended for use in clinical and nonclinical settings. PMID- 11785589 TI - Assessment of the child with altered level of consciousness. PMID- 11785590 TI - Long-term mortality among patients discharged alive after out-of-hospital cardiac arrest does not differ markedly compared with that of myocardial infarct patients without out-of-hospital cardiac arrest. AB - The aim of our research was to study the long-term prognosis among patients discharged alive after an out-of-hospital cardiac arrest (OHCA) in comparison with patients discharged alive after acute myocardial infarction (AMI) without OHCA, and also to study the long-term influence of AMI in connection with OHCA. Our research was conducted in the municipality of Goteborg. We retrospectively studied patients discharged from hospital 1990-91 after an OHCA of cardiac aetiology and patients discharged after an AMI without prehospital cardiac arrest. During 1980-98, we studied all patients discharged alive after OHCA of cardiac aetiology, divided into groups of precipitating AMI and no AMI. The study includes 48 patients discharged alive after an OHCA 1990-91, 30 (62%) of whom had a simultaneous AMI and 1425 patients with an AMI without OHCA. Compared with AMI survivors, survivors of an OHCA of cardiac origin were younger but had more frequently a history of congestive heart failure. Their mortality rate during the subsequent 5 years was 46%, compared with 40% among survivors of an AMI (NS). The 5-year mortality rate among patients with an OHCA precipitated by an AMI was 40%. When correcting for differences at baseline, the adjusted risk ratio for death among patients with an OHCA of cardiac origin was 1.2 (95% CI 0.8-1.8) compared with patients with an uncomplicated AMI. During 1980-98, 215 patients were judged as having an OHCA precipitated by an AMI and 115 patients had an OHCA of cardiac aetiology but no simultaneous AMI. Five-year mortality was 54% and 50% respectively (NS). It is concluded that survivors of an OHCA of cardiac origin differed from survivors of an uncomplicated AMI in that they were younger and more frequently had a history of cardiovascular disease. Their 5-year mortality after discharge was similar to that of survivors of an AMI without a prehospital cardiac arrest, even after adjusting for differences at baseline. PMID- 11785591 TI - Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest? AB - We aimed to investigate the utility of end-tidal carbon dioxide concentration as a prognostic indicator of initial outcome of resuscitation, we conducted a prospective study of EtCO2 in adult victims of out-of-hospital non-traumatic cardiac arrest. We prospectively studied 139 adult patients. The initial, final, average, minimal and maximal EtCO2 was significantly higher in resuscitated patients than in non-resuscitated patients. Using an initial, average and final EtCO2 value of 10 mmHg correctly identified 100% of the patients who were subsequently resuscitated with an acceptable specificity (74.1%; 90%; 81.4%). Important observation from this study is that none of the patients with an average, initial and final EtCO2 level of less than 10 mmHg were resuscitated. Data from this prospective clinical trial indicate that initial, average and final EtCO2 monitoring during CPR is correlated with resuscitation. End-tidal CO2 monitoring has potential as a noninvasive indicator of cardiac output during resuscitation and a prognostic indicator for resuscitation. PMID- 11785592 TI - Comparison of oral and intravenous morphine following acute injury in children. AB - The objective of this research was to examine the speed of onset and effectiveness of pain relief between oral and intravenous morphine in acutely injured children. An observational study of children aged 3 to 13 years with closed forearm fractures was performed in three accident and emergency departments. The study gathered information on age, gender, body weight, time of arrival, dose, route and time of morphine administration. Pain assessment using a Faces Scale was documented on arrival and repeated at 10, 30 and 60 minutes after morphine was given. Forty-seven children were studied. Of these, 25 were given intravenous morphine, 22 were given oral morphine. There was no statistically significant difference in age, body weight or time until morphine was administered. The change in median pain scores was analysed using the Mann Whitney U test. This showed that there was a statistically significant reduction in pain score in the intravenous group compared with the oral group between arrival and 10 minutes after giving morphine and between arrival and 60 minutes after giving morphine. Intravenous morphine appears to give more rapid onset and more prolonged pain relief than oral morphine for children with acute injuries. We recommend that in accident and emergency departments where staff are experienced in paediatric cannulation, morphine should be given via the intravenous route in acutely injured children. However we do not advocate inexperienced staff attempting multiple venepunctures in a child resulting in increased anxiety. PMID- 11785593 TI - Comparison of alfentanil and morphine in the prehospital treatment of patients with acute ischaemic-type chest pain. AB - Patients with acute myocardial ischaemic pain would benefit from rapid pain relief. The clinical usefulness of alfentanil, which has a rapid onset of action, was therefore assessed as the initial pain relieving opioid in patients suffering from acute myocardial ischaemic pain. The effects of alfentanil were compared with those of morphine in the prehospital treatment of 40 haemodynamically stable patients suffering from acute ischaemic-type chest pain. After initial assessment, the patients were given either 0.5 mg alfentanil or 5 mg morphine intravenously in a randomized double-blind fashion. The dose was repeated 2 minutes later if severe pain persisted. Arterial pressure, heart rate, respiratory rate and pain expressed on a visual analogue scale was measured before and at 2, 4, 6, 10 and 15 minutes after administration of drugs. After randomization, four patients were excluded. Sixteen patients received alfentanil and 20 patients morphine. Pain relief was faster (p < 0.005) in the alfentanil group than in the morphine group. Alfentanil was found to provide effective analgesia during the follow-up period of 15 minutes. No haemodynamic or respiratory side effects occurred. It is concluded that alfentanil is an effective analgesic in the prehospital treatment of myocardial ischaemic pain. PMID- 11785594 TI - Community-acquired pneumonia--implementation of a prediction rule to guide selection of patients for outpatient treatment. AB - The aim of this study was to determine the outcomes of outpatient treatment of community-acquired pneumonia (CAP) when a prediction rule was followed by emergency physicians to guide the selection of patients. This was a prospective observational study conducted at the emergency department of a university affiliated hospital in Hong Kong, China. A clinical prediction rule was implemented to guide the selection of patients with CAP for outpatient treatment. All subsequent hospitalizations gial presentation were recorded, and the reasons were assessed. The utilization of the observation unit was incorporated into the treatment algorithm. Of 72 patients with CAP followed up as outpatients, 60 (83.3%) were treated successfully, nine (12.5%) required subsequent hospitalization within 30 days, and three (4.2%) were lost to follow-up. None of the patients died, and none required admission to the intensive care unit. Factors associated with subsequent hospitalization include: tuberculosis, underlying malignancy, persistent fever, comorbidity (rheumatoid arthritis and severe osteoporosis), intravenous drug addiction and alcoholism. The observation ward was utilized in 10 (16.7%) patients successfully treated as outpatients. It is concluded that the prediction rule can be safely implemented as a guide for emergency physicians. The short-stay observation unit may be usefully employed for treating low-risk CAP. PMID- 11785595 TI - Imported malaria in the 1990s: a review of 101 patients. AB - Imported malaria remains a difficult problem in nonendemic areas of the world. We describe the clinical presentation of 101 cases of malaria diagnosed at the Leuven University Hospital between 1 January 1990 and 31 December 1999. Ninety three patients (92%) presented initially at the emergency department. Diagnosis was initially not suspected by the referring physician in 48 patients (47%). Plasmodium falciparum was the commonest species, accounting for 67% of the cases. All but three patients had fever as the presenting symptom, but only 10 had a typical tertian fever pattern. Haemolytic anaemia, thrombocytopenia and hyponatraemia represented a typical triad in 20% of the cases. Only 13% of the malaria patients had taken correct chemoprophylaxis according to WHO recommendations. Eighty-three per cent of the patients were admitted to the hospital with a median duration of hospitalization of 4 days. All complications occurred in cases with P. falciparum. All patients were cured. PMID- 11785596 TI - Epidemic dystonia in Cork. AB - We describe a case series of five patients with unusual presentations of acute dystonia seen over a 2-week period. Haloperidol, prescribed and allegedly purchased 'on the street', was thought to be a possible cause in each case. Bizarre clinical presentations and delayed onset of symptoms may make diagnosis difficult. A high index of suspicion combined with a careful drug history is essential. PMID- 11785597 TI - Ciguatera poisoning: a global issue with common management problems. AB - Ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food borne illness related to contaminated fish consumption. As many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the Pacific Basin, Indian Ocean and Caribbean. Isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as Europe and North America. Increase in travel between temperate countries and endemic areas and importation of susceptible fish has led to its encroachment into regions of the world where ciguatera has previously been rarely encountered. In the developed world, ciguatera poses a public health threat due to delayed or missed diagnosis. Ciguatera is frequently encountered in Australia. Sporadic cases are often misdiagnosed or not medically attended to, leading to persistent or recurrent debilitating symptoms lasting months to years. Without treatment, distinctive neurologic symptoms persist, occasionally being mistaken for multiple sclerosis. Constitutional symptoms may be misdiagnosed as chronic fatigue syndrome. A common source outbreak is easier to recognize and therefore notify to public health organizations. We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu. All responded well to intravenous mannitol. This is in contrast to a fifth patient who developed symptoms suggestive of ciguatoxicity in the same week as the index cases but actually had staphylococcal endocarditis with bacteraemia. In addition to a lack of response to mannitol, clinical and laboratory indices of sepsis were present in this patient. Apart from ciguatera, acute gastroenteritis followed by neurological symptoms may be due to paralytic or neurotoxic shellfish poisoning, scombroid and pufferfish toxicity, botulism, enterovirus 71, toxidromes and bacteraemia. Clinical aspects of ciguatera toxicity, its pathophysiology, diagnostic difficulties and epidemiology are discussed. PMID- 11785598 TI - Epidemiological profile of geriatric patients admitted to the emergency department of a university hospital localized in a rural area. AB - The number of geriatric patients admitted to the accident and emergency department is growing. These patients also present increasing functional dependence and a large panel of associated diseases and associated problems. For the purpose of describing this phenomenon, we prospectively studied the epidemiology of patients 75 years and older entering the emergency department of a university hospital localized in a rural area. From January 1996 up to January 1997, 1298 patients aged 75 years or older were admitted to the emergency department. This age group represented 12.3% of all the patients admitted during the period. The gender distribution was almost equal: 56% were female and 44% male. Most of them (75%) were referred by their general practitioner although 15% came spontaneously. The most common complaints were, in decreasing order: general condition impairment (21.5%), dyspnoea (15%), falls and traumas (15%), abdominal problems (13%), thoracic pain (9%), syncope, dizziness (7%) and stroke (5.5%). Hospitalization was necessary in 69% of cases. Among the patients coming spontaneously a larger proportion (55%) were sent back home compared with only 25% of those referred by their general practitioner. PMID- 11785599 TI - A prospective study of tracheal intubation in an emergency department in Hong Kong. AB - Emergency department (ED) doctors often intubate patients, however no data was available in Hong Kong on this aspect. Our study was to assess the competency of ED doctors in intubating critical patients in a typical ED in Hong Kong. Between March and August 1999, in an urban hospital with an emergency physician training programme, all doctors, after performing any tracheal intubation, were required to fill in a pro forma designed for the study. Data collected included the training status of the intubator, the number of intubation attempts, intubation methods and complications. A total of 214 ED patients required advanced airway management including 87 (41%) patients in cardiopulmonary arrest; 207 (97%) of them were successfully intubated by ED doctors (76 by specialists, 61 by trainees, 70 by residents) and 90% were successful in the first attempt. The remaining seven patients' airway control was eventually managed by anaesthetists who successfully intubated six patients and performed cricothyrotomy for one patient. Rapid sequence intubation was performed in 70 (33%) patients by ED doctors and specialists. There were 30 (14%) patients successfully intubated using sedative agents alone. Twenty-two (10%) patients were found to have a total of 32 complications including 13 patients with oesophageal intubation, seven with soft tissue damage, four with desaturation, three with bronchial intubation, three with hypotension, one with dental trauma, one with dysrhythmia. The majority of ED intubations for critically ill patients were performed by ED doctors with high success rate and few major complications. PMID- 11785600 TI - The role of L-arginine and neutrophils on incisional wound healing. AB - Although arginine plays an important role in many aspects of inflammation and wound healing, the mechanism is not clear. We aimed to evaluate the effect of L arginine administration on wound healing and neutrophil activity and on the interaction of these effects. Sixteen rats were divided into two groups: control group and L-arginine group. L-arginine was given intraperitoneally. The rats underwent incisional wounding and were killed on the 7th day of wounding. Blood neutrophil counts, neutrophil adhesivity index, tensile strengths and hydroxyproline level of skin were determined, histopathological and electron microscopical evaluation of healing was performed. Wound scores in the control group were significantly lower (p < 0.05). Hydroxyproline and collagen levels of skin were significantly increased in the L-arginine group (p < 0.05). Blood neutrophil counts and neutrophil adhesivity index in the L-arginine group were significantly increased (p < 0.05), as were the inflammatory cells in the skin. L arginine may be used during the first phase of healing to induce inflammation in high risk patients. PMID- 11785601 TI - A case of child abuse: haloperidol poisoning of a child caused by his mother. AB - This presentation focused on a hyperactive child admitted to the emergency department because of ataxia and imbalance. It was later discovered that the child had been abused by his mother. In cases where there is conflict between the clinical findings, the patient and the family's history in a clinical state which cannot be explained satisfactorily by the medical staff, the need for taking the history again from other relatives whilst taking into account the parents' physiological well-being, is time well spent. PMID- 11785602 TI - The management of stab wounds to the heart with laceration of the left anterior descending coronary artery. AB - Penetrating cardiac injuries are an increasing cause of traumatic deaths in urban areas. The management of these injuries has undergone a transition from simple pericardiocentesis to cardiac ultrasound evaluation in the stable patient, and emergency thoracotomy and repair of myocardial wounds in the unstable patient in extremes. The incidence of traumatic coronary artery injury is not accurately known because not all victims are examined. With the improvement in emergency medical services, including speed of transportation of these patients, better resuscitation, and knowledgeable use of cardiac ultrasound or emergency room thoracotomy, more patients with coronary artery injuries will survive and reach the operating room. The operative management of the injured coronary artery is dependant on the location of the injury and whether there is myocardial dysfunction. Distal injuries with small myocardial infarction should be treated by ligation alone. Proximal injury and those injuries associate with larger area of ischaemia or infarction are best treated with coronary artery bypass. The role of cardiopulmonary bypass pump in these patients should be evaluated depending on the homodynamic stability of the patient. We present two cases of cardiac stab wounds with transection of the left anterior descending (LAD), which were successfully managed. A literature review regarding the management of combined cardiac and coronary artery injuries is also provided. PMID- 11785603 TI - The idiopathic hypereosinophilic syndrome. AB - Idiopathic hypereosinophilic syndrome (HES) is empirically defined as the presence of prolonged eosinophilia without an identifiable underlying cause, and with evidence of end-organ dysfunction. Virtually any organ system may be involved, most frequently the heart, the central and peripheral nervous system, the lungs and the skin. We report on two clinical cases where the diagnosis of HES, with all the conventional criteria met, was proposed. In the first patient with HES, cardiac and pulmonary involvement was present. Skin changes and lung involvement were observed in the second reported patient with HES. In both patients there was prompt improvement of all clinical signs and symptoms of HES soon after treatment with methylprednisolone was begun. In the first patient long term methylprednisolone therapy was healed successfully. For 2 years he has shown no clinical signs or symptoms of HES. The second patient is still undergoing long term therapy with 4 mg of methylprednisolone daily. The histologic findings of the skin biopsy in the second patient were not typical for HES, but skin changes completely healed after corticosteroid therapy. This could mean that that the described skin changes were one of the HES skin manifestations. The other possibility is that the skin changes emerge in coincidence with HES. PMID- 11785604 TI - A case of traumatic globe luxation. AB - We observed a case of traumatic globe luxation. A 26-year-old man who was sitting at the back seat of the car without fastening his safety belt was admitted to the emergency room after an automobile accident. He was in semi-comatose condition. His left globe was dislocated anteriorly, and the lids were tightly closed behind it. No laceration was observed in cornea, sclera and extraocular muscles. The pupil was dilated and did not respond to light stimulation. Computerized tomography scan analysis revealed a normal optic nerve, but multiple fractures in the nasal, inferior and temporal walls of the orbit and in the nasal bone. Phthisis of the eye was detected by the end of second month. We believe that the back seats of automobiles should also be furnished with air bags for better security of passengers. PMID- 11785605 TI - Chronic constipation--a lethal danger in patients with systemic scleroderma. AB - The gastrointestinal tract is one of the main sites of manifestation of systemic scleroderma. We describe a case of a 62-year-old patient with systemic scleroderma and progressive severe constipation that led to stercoral obstruction and perforation. We make a brief review of the literature on the gastrointestinal manifestations and the management of systemic scleroderma. PMID- 11785606 TI - Life-threatening uvular angioedema caused by Ecbalium elaterium. AB - Ecbalium elaterium, known as the wild or squirting cucumber, is a hairy perennial herbaceous vine of the Cucurbitaceae family, endemic to the Mediterranean region. All parts of the plant are toxic, particularly the gherkin-like fruits. It is frequently used in the treatment of sinusitis by nasal aspiration in some parts of the Mediterranean. The studies regarding to Ecbalium elaterium, argue that it has an anti-inflammatory characteristic. Two cases of uvular oedema have been ascribed to the undiluted use of this substance. Since they can threaten life, similar cases arising with the improper use of herbals should not be ignored in the emergency department. In this paper we present a life-threatening uvular angioedema caused by nasal aspiration of undiluted juice of squirting cucumber. PMID- 11785607 TI - Preserving balance in forensic psychiatry. PMID- 11785608 TI - Predictors of adolescent psychopathy: the role of impulsivity, hyperactivity, and sensation seeking. AB - Clinical applications to psychopathy encompass downward extensions to adolescent populations. In alliance with clinical practice, several prominent researchers have formulated prediction models for adolescent psychopathy that include various forms of behavioral dysregulation, including impulsivity, attention deficit/hyperactivity disorder (ADHD), and sensation seeking. As a cross sectional study, the current investigation systematically examined behavioral dysregulation in 79 male adolescents who, as a result of adjudication, were placed them in a maximum-security facility. Impulsivity appeared to be the best predictor of both psychopathy and conduct problems. In addition, conduct disordered symptoms were predicted mostly by impulsivity, with minor contributions from sensation seeking and ADHD symptoms. PMID- 11785609 TI - Commentary: you can observe a great deal by just looking. PMID- 11785610 TI - Six adoptees who murdered: neuropsychiatric vulnerabilities and characteristics of biological and adoptive parents. AB - This article is the first to document the perinatal trauma and neuropsychiatric impairment of a sequential sample of male adoptees who committed murder. It also is the first to report objectively verifiable psychopathology and violence in their biological and adoptive parents. It explores the interaction of these variables in the genesis of violence. Subjects were six adopted murderers on whom data regarding biological and adoptive parents could be obtained. In all six cases, central nervous system (CNS) development was compromised in utero or perinatally. In adolescence and/or young adulthood, three met DSM-IV criteria for Bipolar Mood Disorder, one for Schizophrenia, and two for Schizoaffective Disorder. All subjects had at least one psychotic biological parent. In five cases, subjects were adopted into psychotic or violent households. There was no evidence of a specific "bad seed" for violence. Adoptees' intrinsic vulnerabilities to psychoses and to the impulsiveness and emotional lability often associated with early brain trauma, coupled with maltreatment, predisposed them to homicidal violence. As such, these subjects were similar to other extraordinarily violent, nonadopted, offenders. Conscious feelings regarding adoption did not contribute to the subjects' homicidal rages, so much as did conscious rage toward abusive, rejecting adoptive families. PMID- 11785611 TI - Commentary: sex and violence. PMID- 11785612 TI - "A fool for a client": print portrayals of 49 pro se criminal defendants. AB - In the United States, an accused person has a constitutionally protected right to serve as his or her own lawyer, even if this means he or she has "a fool for a client." In the current study, information from more than 2,700 articles in the LEXIS "U.S. New, Combined" database was used to produce what the authors believe is the psychiatric literature's first characterization of a group of pro se criminal defendants. The sample's 49 defendants had a broad age range (18-75 years) and a broad range of educational backgrounds (9 to >20 years of formal schooling). Men, attorneys, persons with other advanced degrees, and unemployed persons formed disproportionately large fractions of the sample, compared with the general population. The defendants faced a broad variety of charges; homicide was the most common one. Many had reasonable motives for representing themselves, such as dissatisfaction with their lawyers or believing that they could do as well without attorney representation. Defendants' apparent reasons for representing themselves fell into one of three categories: eccentric (16 defendants), ideological (4 defendants), and personal (19 defendants). These categories offer courts and evaluators three possible conceptualizations of a pro se defendant's behavior, outlook, and motivation. PMID- 11785613 TI - Juvenile and young adult mentally disordered offenders: the role of child neuropsychiatric disorders. AB - A retrospective study of the prevalence of child neuropsychiatric disorders was done involving pervasive developmental disorder (PDD), attention deficit/hyperactivity disorder (ADHD), and Tourette syndrome in young offenders (15-22 years, n = 126) consecutively referred for presentencing forensic psychiatric investigation (FPI) in Stockholm, Sweden. Most offenders were referred for FPI because of serious offenses. Case report sheets were prepared, and retrospective neuropsychiatric DSM IV diagnoses were made by the first two authors. For best-estimated diagnoses, the case report sheets were then submitted to the fifth author, a child neuropsychiatrist with expertise in this area. Fifteen percent of the subjects had a definite diagnosis of ADHD, and another 15 percent had PDD, including 12 percent PDD not otherwise specified (NOS) and 3 percent Asperger syndrome. Autistic disorder was not found in any case. Tourette syndrome occurred in two percent of the cases. The rate of PDD is particularly striking. Neuropsychiatric diagnoses had been determined in the FPI in only a few cases. The contribution of constitutional problems to later criminal development may have been underestimated. PMID- 11785614 TI - Juveniles adjudicated incompetent to proceed: a descriptive study of Florida's Competence Restoration program. AB - Although competence to stand trial is perhaps the most studied area of mental health law, most of the research has been focused on adults. This study describes a population of 471 juveniles committed for treatment/habilitation and restoration of their competence to proceed in the delinquency process. This population differed from their adult counterparts in important ways. For example, 58 percent of the juveniles had a diagnosis of mental retardation, and 57 percent of the juveniles with an Axis I diagnosis also had a diagnosis of conduct disorder. Only 17 percent had a diagnosed psychotic disorder. Diagnoses among cohorts of adults found incompetent differ markedly. However, similar to adult defendants who are adjudicated incompetent to proceed, the majority of these children were returned to court after treatment staff determined that they were competent to proceed. Contrary to expectation, there were no significant age related differences with respect to the recommendation of clinical staff regarding restoration of competence. The data suggest the need for further research examining that subset of children in the juvenile justice system whose competence to proceed is questionable. PMID- 11785615 TI - Practical methods for detecting mendacity: a case study. AB - This study demonstrates the concurrence of the use of objective verbal and nonverbal signs and lying. President Clinton's Grand jury Testimony of August 17, 1998, was examined for the presence of 23 clinically practical signs of dissimulation selected from 64 peer-reviewed articles and 20 books on mendacity. A segment of his testimony that was subsequently found to be false was compared with a control period during the same testimony (internal control). A fund raising speech to a sympathetic crowd served as a second control (external control). The frequencies of the 23 signs in the mendacious speech were compared with their frequencies during the control periods, and the differences were analyzed for statistical significance. No clinical examination was performed nor diagnosis assigned. During the mendacious speech, the subject markedly increased the frequency of 20 out of 23 signs compared with their frequency during the fund raising control speech (p < .0005). He increased the frequency of 19 signs compared with their frequency during the control period of the same testimony (p < .003). The 23 signs may be useful as indicators of the veracity of videotaped and scripted testimony. If these findings are confirmed through further testing, they could, with practice, be used by psychiatrists conducting interviews. PMID- 11785616 TI - The ethical use of psychology in criminal investigations. PMID- 11785617 TI - Reply to Schafer: defending the facts. PMID- 11785618 TI - Reply to Schafer: exploitation of criminal suspects by mental health professionals is unethical. PMID- 11785619 TI - Reply to Schafer: ethics and state extremism in defense of liberty. PMID- 11785620 TI - Reply to Schafer: doing harm ethically. PMID- 11785621 TI - Are persecutory delusions amenable to treatment? PMID- 11785622 TI - Prosecution of illicit drug use during pregnancy: Crystal Ferguson v. City of Charleston. PMID- 11785623 TI - Medication of criminal defendants. PMID- 11785624 TI - Standards for informed consent in recovered memory therapy. PMID- 11785625 TI - Chemical speciation and sequential extraction of Mn in workroom aerosols: analytical methodology and results from a field study in Mn alloy plants. AB - Workers in the Mn alloy producing industry are exposed to aerosols containing a variety of Mn compounds (MnO, MnO,, Mn2O3, Mn3O4, FeMn and SiMn). This paper reports a novel four-step chemical speciation/ fractionation procedure developed for characterisation of workroom aerosols collected in Mn alloy producing plants. The following components of the aerosol have been quantified: "water soluble" Mn dissolved in 0.01 M ammonium acetate: Mn0 and Mn2+ dissolved in 25% acetic acid; Mn3+ and Mn4+ dissolved in 0.5%) hydroxylamine hydrochloride in 25%) acetic acid; and "insoluble" Mn digested in aqua regia and hydrofluoric acid. Dissolution of pure Mn compounds with well-defined stoichiometries were essentially complete in the respective leaching steps with detectable amounts of < 1% in others. Recoveries of a mixed quality control sample were also acceptable in the range 92 97% for the different oxidation states. The levels measured in the inhalable and respirable fractions in three Mn alloy producing plants were approximately 300 and 35 microg m(-3) of total Mn, respectively. The most obvious feature of the speciation results is that none of the work areas is characterised by a single Mn contaminant. The predominant oxidation states in the inhalable aerosol fraction are Mn0 and Mn2+ independent of job functions/departments. The occurrence of insoluble Mn compounds in both the inhalable and respirable aerosol fractions is significantly higher during production of SiMn. PMID- 11785626 TI - Aluminium uptake and excretion in potroom workers of a new primary aluminium smelter during the construction stage. AB - The aim of this study was to define bio-accumulation and excretion patterns of aluminium in newly employed potroom workers as well as changes in ambient aluminium levels in the potrooms of a modern aluminium smelter during the plant construction stage and one year into full production. A study was carried out on 115 newly employed volunteer potroom workers at various intervals, over a total period of 36 months. Before commencement of employment a structured questionnaire was completed by all study participants and the first collection of blood and urine specimens took place. As none of the subjects had ever worked in the aluminium industry before, they also served as their own controls. Atomic absorption spectroscopy was used to measure the aluminium content in the biological fluids and the content of the metal in the ambient air of the potrooms. Significantly, the study found an early and marked biological response to inhalation of very low levels of airborne aluminium. After only 12 months, the mean concentration of aluminium in serum had almost doubled; thereafter it levelled off. A mixed model analysis did not find any differences in the concentrations of aluminium in the serum of the subjects since the variation between subjects at any given time was much smaller than the variation within subjects. This may be an indication of the pronounced effect of aluminium inhalation on the kinetics of this metal in the human body. Furthermore, urinary excretion of aluminium by the potroom workers showed a linear increase reaching a concentration of only 49 microg l(-1) at the 36 month stage, suggesting a slow rate of elimination. PMID- 11785627 TI - Particle size and chemical species 'fingerprinting' of aerosols in primary nickel production industry workplaces. AB - A field study was conducted at a range of worksites at a number of plants, for two companies, in the primary nickel production industry. The aim of the field study was to provide direct measurements of the distributions of both particle size and relevant nickel species groups (soluble, sulfidic, metallic and oxidic). and to use the data to characterize health-relevant aerosol exposures of workers at the worksites in question. Since there was no commercially-available sampler that could provide samples of sufficient quantity to enable chemical speciation for the species fractions of interest, as well as particle size distribution information, new instrumentation was developed, based on a modified version of the Andersen cascade impactor, incorporating a porous foam media top stage that produced particle classification over the upper end of the inhalable range (Kerr, Vincent and Ramachandran, Annals of Occupational Hygiene, 2001, in the press). This modified-Andersen sampler was used in extensive field studies, along with other sampling instruments, including, in particular, the IOM personal inhalable aerosol sampler. The results of the field study provided results that could be represented succinctly in terms of the distributions of the four nickel species groups and the three health-related particle-size fractions: inhalable, thoracic and respirable. They showed that, for practical purposes, the distributions of the four nickel species groups were consistently uniform across the full range of particle-size distribution. For the purpose of characterizing the distribution of nickel species for each worksite, this finding enabled incorporation of additional data taken at those same sites using the IOM personal inhalable aerosol sampler. This yielded a data set sufficient to permit the development of exposure 'fingerprints' for each worksite. Such 'fingerprints' make it possible for the occupational hygienists at the plants in question to estimate workers' exposure to individual nickel species fractions based on measurement only of overall inhalable nickel. In addition, by reference to the differing threshold limit values (TLV) for the various nickel species, the 'fingerprints' also allow the individual worksites to be characterized by hazard indices (in the form of 'equivalent sulfidic fractions', or ESFs) that reflect the weightings of the risks experienced by workers at each worksite. PMID- 11785628 TI - Ultraviolet absorbance in lakes near the metal smelters in Sudbury, Canada. AB - Ultraviolet (UV)-dissolved organic carbon (DOC) models were developed using surface samples collected from 58 lakes located 8-128 km from the metal smelters in Sudbury, Canada. Highly significant (R2 = 0.93-0.95) relationships were found between absorbance coefficients (K(a)lambda) and DOC within the UV-A and UV-B range (310, 30, 365 nm). Changes in UV absorbance with water depth were assessed in a subset of four lakes. Two study lakes with intermediate levels of DOC (DOC = 10-2.5 mg L(-1)) showed very marked depth related absorbance profiles, with evidence of photodegradation and much reduced absorbance in surface waters, particularly evident in late summer. These changes may affect complexation of metals and UV habitat characteristics for sensitive biota. These findings suggest that UV absorbance is an important variable for inclusion in long-term monitoring programs. PMID- 11785629 TI - Peracute vanadium toxicity in cattle grazing near a vanadium mine. AB - Animals may act as bioindicators for potential human health problems associated with mining and refining. Eight cattle died after a vanadium mine dam collapsed close to the area in which they were grazing. Necropsies were conducted on five cattle. Affected animals had shown a watery bloody diarrhea, red urine and listlessness before collapsing. On necropsy (n = 5) there was a moderate bilateral multifocal granulomatous-like conjunctivitis. The most prominent lesions were eosinophillic granulomatous-like inflammation of the thymus, mediastinal and mesenteric lymph nodes, oesophagus, abomasum and colon. There was also marked hyperaemia of the abomasal mucosa with petechiation. Pulmonary and tracheal haemorrhage was also present. Histopathology showed severe inflammatory cell infiltration (mainly eosinophils with lesser numbers of neutrophils and macrophages) of lymphoid tissue associated with the thymus, lymph nodes, esophagus, abomasum, colon and conjunctiva. There were also areas of tissue necrosis, congested blood vessels and haemorrhage. Conjunctival lesions point to a systemic rather than a local effect as the cattle in this case died following ingestion rather than inhalation of vanadium. The causal relationship between intoxication and death is conventionally based on the level of that toxin present in tissues at necropsy. The variability in demonstrating vanadium in biological samples may have been due to the rapid excretion of vanadium by the living animal, or the solubility of the salts, which results in the substance leaching into the fluid portion of the samples. Cross-reactions with colorimetric tests for arsenic should also be noted. PMID- 11785630 TI - Copper, manganese, cobalt and selenium concentrations in liver samples from African buffalo (Syncerus caffer) in the Kruger National Park. AB - Animals may act as bio-indicators for the pollution of soil, air and water. In order to monitor changes over time, a baseline status should be established for a particular species in a particular area. The concentration of minerals in soil is a poor indicator of mineral uptake by plants and thus their availability to animals. The chemical composition of body tissue, particularly the liver, is a better reflection of the dietary status of domestic and wild animals. Normal values for copper, manganese and cobalt in the liver have been established for cattle but not for African buffalo. As part of the bovine tuberculosis (BTB) monitoring programme in the Kruger National Park (KNP) in South Africa, 660 buffalo were culled. Livers (n = 311) were randomly sampled in buffered formalin for mineral analysis. The highest concentrations of copper were measured in the northern and central parts of the KNP, which is downwind of mining and refining activities. Manganese, cobalt and selenium levels in liver samples indicated neither excess nor deficiency; however, there were some significant area, age and gender differences. The results will be useful as a baseline reference when monitoring variations in the level and extent of mineral pollution on natural pastures close to mines and refineries. PMID- 11785631 TI - Partitioning of Zn, Pb and Cd in river sediments from a lead and zinc mining area using the BCR three-step sequential extraction procedure. AB - The extent of pollution was investigated in sediments collected along the course of the river Meza and its tributaries in the lead and zinc mining area of the Mezica valley (Slovenia). In order to evaluate the heavy metal burden, total concentrations of Zn, Pb and Cd were determined and the partitioning of these metals between the easily and sparingly soluble sediment fractions was performed by the use of the slightly modified BCR sequential extraction procedure. The quality of analytical data was checked with Certified Reference Material CRM 601. Good agreement between the determined and certified or indicative metal concentrations was obtained. In order to estimate the natural and anthropogenic inputs of Zn, Pb and Cd in the sediments, normalisation to Al was applied. The results of the partitioning study indicate that Zn prevails in the most sparingly soluble fraction and is distributed between organic matter and sulfides, while a smaller proportion is found in the easily soluble fraction. Pb is distributed mainly between organic matter and sulfides, whereas Cd is predominantly associated with the most sparingly soluble fraction. Data from the normalisation procedure indicate that the anthropogenic inputs of Zn, Pb and Cd correlate with the very high total metal concentrations determined in sediments. The highest total Zn, Pb and Cd concentrations (16.3. 9.3 and 0.13 g kg(-1), respectively) were found in the sediment of the Helena rivulet, arising from former mining activities. In spite of the relatively low easily soluble metal fractions in the sediment, the concentrations of metals in these fractions are high, owing to the extremely high total metal concentrations. These data indicate severe pollution of the terrestrial and aquatic environment. PMID- 11785632 TI - The polycyclic aromatic hydrocarbon and geochemical biomarker composition of sediments from voes and coastal areas in the Shetland and Orkney Islands. AB - Marine sediments from coastal areas and voes in the Shetland and Orkney Islands were analysed for parent and branched 2- to 6-ring polycyclic aromatic hydrocarbons (PAHs) and geochemical biomarkers. Where possible 14 sediment samples were collected at random from each of 17 Shetland and 9 Orkney sites. The wide range of total PAH concentrations in sediments (i.e., < LOD up to 22619 ng g(-1) dry weight) was indicative of a variety of anthropogenic activities and different sediment types associated with the specific locations. Low PAH concentrations were determined in sandy sediments from areas of limited boat activity. The highest PAH concentrations were found in muddy sediment close to a boat repair yard. PAH concentration ratios were consistent with the main source of these compounds, in most areas, being pyrolysis. Geochemical biomarker (triterpane and sterane) profiles from the sediment were indicative, for some areas, of limited petrogenic input. Punds Voe was the only voe to show evidence of North Sea oil. PAH profiles were similar across sites within each island group, with any differences attributable to known local sources of PAHs. However, there was a clear difference in the PAH profiles of Shetland and Orkney sediments, with Orkney sediments having a higher proportion of the lighter alkylated PAHs. PMID- 11785633 TI - Polyaromatic hydrocarbon concentrations and patterns in sediments and surface water of the Mansfeld region, Saxony-Anhalt, Germany. AB - The composition and spatial distribution of polyaromatic hydrocarbons (PAHs) and their relation to potential pollution sources were investigated in the Bose Sieben Creek, Saxony-Anhalt, Germany, using two techniques: semipermeable membrane devices (SPMDs) and sediment analysis. SPMD is an integrative device that passively samples hydrophobic chemicals of low to moderate molecular weight (< 600 Da) in water. SPMDs were placed in water for 34 days at three sites where sediments were also sampled. Fifteen PAHs were determined in SPMDs and in sediment samples to evaluate the concentration levels and specific PAH patterns. Time-weighted average aqueous PAH concentrations were estimated from the PAH amount accumulated in SPMDs during the deployment period using previously reported sampling rates. Sediment-water partition coefficients were used to estimate PAH concentrations in pore water from sediments. Calculated pore water concentrations were, on average, almost three orders of magnitude higher than those calculated from SPMDs. Thus, in addition to contamination from other sources, the water concentration at the sampling sites might be elevated due to contaminant mobilization from historically contaminated sediments. Relative PAH patterns from SPMDs and sediment were compared using principal component analysis, and were correlated with the PAH patterns from different potential contamination sources, including Theisen sludge, one of the by-products of the smelting process for copper production in the region in the past, which is likely to be the main contamination source of PAHs. Moreover, three origin indices (concentration ratios of PAH isomer pairs) were used to evaluate the suitability of these compounds as tracers to distinguish between the contamination arising from different sources. The evaluation of contaminant patterns permits the conclusion that the PAHs are of pyrolytic, industrial origin, possibly including contamination by Theisen sludge, and rules out a petrogenic source for the hydrocarbons. PMID- 11785634 TI - Biliary PAH metabolites and EROD activity in flounder (Platichthys flesus) from a contaminated estuarine environment. AB - The present study in the Firth of Forth, Scotland, emphasises the usefulness of biliary metabolite measurements in estuarine monitoring using the flounder (Platichthys flesus). The short time scale (a few hours) of response to polycyclic aromatic hydrocarbon (PAH) exposure, allowed clearer interpretation of trends and differences between sites. Such differences and trends in the metabolite data were not as apparent from 7-ethoxyresorufin O-deethlyation (EROD) activity measurements, which were likely to have been blurred by the movements of flounder between sites. Statistical differences were not observed in EROD activity in flounder from the Firth of Forth (ANOVA, P = 0.065). The biliary metabolites showed statistical differences between the uppermost site of Longannet and Port Edgar, in the outer Firth, for both the 1-OH pyrene and 2-OH naphthalene metabolites (ANOVA, Tukeys, P = 0.012 and 0.022 respectively). There was also a significant correlation between the concentrations of all three individual metabolites (1-OH pyrene, 2-OH naphthalene, I-OH phenanthrene) and the log of the distance downstream from the major PAH input sources of Longannet power station and Grangemouth. Biliary PAH metabolites were shown to better reflect local contamination gradients than EROD activity. This is explained by the relative response times of the two biomarkers and local movements of the flounder in the estuary. PMID- 11785635 TI - The determination of alkylphenols in aqueous samples from the Forth Estuary by SPE-HPLC-fluorescence. AB - Nonylphenol and octylphenol have been identified as endocrine disrupters with the ability to cause reproductive deformities in a number of organisms. A normal phase high-performance liquid chromatography (HPLC) method with fluorescence detection was developed with a mobile phase of cyclohexane/methyl-tertiary-butyl ether (MTBE) (70 + 30). The extraction of the alkylphenols from the water samples was evaluated using solid-phase extraction (SPE) with a C2 packing sorbent. The complete method was validated and the limit of detection calculated to be 0.15 ppb (microg l(-1)). The method was novel for the analysis of specific alkylphenols in an aqueous matrix. A survey of the Forth Estuary in May 2000 resulted in no detectable amounts of nonyl- or octylphenol, whilst a survey during August of the same year produced concentrations ranging from 0.17-1.90 ppb for nonylphenol and 0.17-1.28 ppb for octylphenol. These results are compared with other river and estuarine studies with concentrations considered in terms of toxicity to aquatic organisms. The concentrations determined in the Forth Estuary are consistent with a contaminated though not grossly polluted estuarine system. PMID- 11785637 TI - Determination of butyl-, phenyl-, octyl- and tributylmonomethyltin compounds in a marine environment (Bay of Bengal, India) using gas chromatography-inductively coupled plasma mass spectrometry. AB - Organotin compounds (butyl-, phenyl-, octyl- and tributylmonomethyltin) and inorganic tin were quantified in sea-water and sediments from two harbours and several locations on the southeast coast of India using highly sensitive and selective gas chromatography-inductively coupled plasma mass spectrometry (GC-ICP MS), adopting new extraction and analytical techniques with extremely low detection limits (water, 0.019-0.85 pg l(-1); sediment, 0.23-0.48 ng g(-1)). The concentrations of monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) in sea-water from Tuticorin harbour varied from 0.64 to 4.97, 3.0 to 26.8 and 0.3 to 30.4 ng Sn l(-1), respectively. MBT, DBT and TBT in sediments from harbour areas ranged from 1.6 to 393, 1.3 to 394 and ND (not detected) to 1280 ng Sn g(-1) (dry weight), respectively. Natural methylation in both harbours was established by quantifying tributylmonomethyltin (TBMMT) residues (sea-water, ND-0.19 ng Sn l( 1); sediment, ND-765 ng Sn g(-1) dry weight). In sea-water, octyltins were also determined as monooctyltin (MOT) > dioctyltin (DOT) > trioctyltin (TOT). Butyltin contamination in commercial harbours is evident, but other coastal waters are not contaminated with organotin residues. The high concentration of inorganic tin in estuarine sediment indicates an elevated rate of debutylation in the estuarine environment. Both methylation and debutylation of TBT in Chennai harbour were greater than in Tuticorin harbour. A significant correlation (r2 = 0.75) between total butyltin and organic carbon contents in sediment was found. To our knowledge, this is the first report on the distribution of butyltins and methylated butyltin in sea-water and sediment and octyltins in sea-water in the Indian marine environment. PMID- 11785636 TI - Occurrence of organophosphate esters in surface water and ground water in Germany. AB - The present investigation was carried out to quantify the three organophosphate esters, tributyl phosphate (TBP), tris(2-chloroethyl) phosphate(TCEP) and tris(2 butoxyethyl) phosphate(TBEP), in river, rain and ground water obtained from several locations in Germany, and to compare the data with those obtained about 15 years ago. Additionally, one influent and one effluent sample of waste water from a local waste water treatment plant were investigated. The applied analytical method is based on solid phase extraction (SPE), in order to concentrate polar compounds from water samples, followed by gas chromatography mass spectrometry (GC-MS) of the extracts. A total of 5 1 of the respective water samples was used for extraction purposes and analyte recoveries were all > or = 83%. The detection limit for the target analytes was 1 ng l(-1) and the relative standard deviations for replicate injections (n = 10) were 14.0% for TBP, 12.6% for TCEP and 9.9% for TBEP. The presence of the organophosphorus compounds, TBP, TCEP and TBEP, in Germany has resulted in water concentrations of 17-1,510 ng l( 1) in the Rhine, Elbe, Main, Oder, Nidda and Schwarzbach Rivers. The maximum value of TBP measured in the Rhine River was 17 times lower than the maximum value measured 10 years ago. The maximum value of TCEP measured in the Rhine River was 100 times lower than the maximum value measured in previous investigations. The maximum concentration of TBEP measured in the Elbe River was seven times higher than the value measured 16 years ago. Similar concentrations of TBP, TCEP and TBEP were also detected in ground water and rain water. The highest levels of these compounds were detected in samples of waste water. PMID- 11785638 TI - Gas exchange of OCPs across the air-water interface at the creek adjoining Mumbai harbour, India. AB - The concentrations of organochlorine pesticides (OCPs) such as hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDT) and its metabolite (DDE) and endosulfans were determined in air and water in order to estimate the magnitude and direction of gas flux across the air-water interface at the creek adjoining Mumbai harbour, India. The range of HCH residues in air was found to be between 1.0 and 22.5 pg m(-3) and that in sea-water was between 1.7 to 34.4 ng l(-1) DDT and its metabolite (DDE) residues in air ranged between 2.1 and 80.8 pg m(-3) and in sea-water between 1.4 to 19.2 ng l(-1). The concentrations of beta-endosulfan in air and sea-water samples were found to be 1.0-1.6 pg m(-3) and 1.0-2.6 ng l(-1) respectively. The HCHs revealed positive values of the fluxes (1.001 microg m(-2) d(-1) for alpha-HCH, 0.107 microg m(-2) d(-1) for beta-HCH and 0.455 microg m(-2) d(-1) for gamma-HCH) indicating the tendency to transfer these contaminants from water to air. This implies that the marine water bodies principally act as a source of HCHs. The fluxes for DDTs (p,p'-DDE and p,p'-DDT) also follow the same pattern as HCHs and show high positive values (1.698 microg m(-2) d(-1) for DDE and 2.422 microg m(-2) d(-1) for DDT). The present study suggests the active transfer of these dissolved OCPs into the atmosphere due to volatilization. PMID- 11785639 TI - Diffusional behaviour of metals in a passive sampling system for monitoring aquatic pollution. AB - Passive sampling systems are an emerging technology for detecting pollutants in the aquatic environment. A passive sampling system has been developed based on diffusion through a porous surface to a receiving phase, where the analyte is removed by chelation at a solid phase. The diffusion process can be described by Fickian diffusion through the sampler. The sampler has a well-defined surface area, which permits calibration in terms of concentration. Passive sampling systems can be used to determine pollutant concentrations if the diffusion process can be described and understood within environmental limits. In natural water systems, diffusion coefficients for metal transport across the porous membrane will be affected by external conditions, including biofouling and variation in turbulence and temperature. Uptake rates for the analytes Cu, Cd and Pb have been determined for the complete passive sampling system. Two different cases have been investigated, a batch case, where the bulk concentration decreases with time, and a flow-through case, where the bulk concentration remains constant. Diffusion coefficients were determined for the two conditions and compared with the calculated value obtained for the Stokes-Einstein equation in pure water. Diffusion coefficients for metals were found to be lower than for diffusion in pure water, a difference attributed to the effect of the porous membrane. The effect of the hydraulic conditions on the metal diffusion was studied for both a conventional magnetic stirrer creating turbulence in the system and for a rotated sampler, the latter providing a well-defined boundary layer system. The boundary layer was found to be negligible compared with the diffusion limiting membrane in the presence of sufficient turbulence or if the rotation of the sampler was high. PMID- 11785640 TI - Application of diffusion-based surveys in the district-wide assessment of benzene and select volatile organic compounds in urban environments--a case study from Renfrewshire, Scotland. AB - Benzene (with toluene, ethyl benzene and xylene isomers) concentrations were measured at nine locations in Renfrewshire district between February 1996 and July 1998. Samples were collected by both active and diffusion-based sampling and the compounds were quantified by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The study highlighted the ability of diffusion sampling to provide an effective district-wide assessment of volatile organic compounds (VOCs) in urban environmental assessment. Vehicle movement was confirmed as the dominant influence on benzene and associated VOCs in the atmosphere, with strong variations in monthly average concentrations across the study area. For benzene, peak monthly averages were observed on the order of 5-6 ppb v/v, with minimum values of < <0.5 ppb v/v. The impact of a major traffic intervention on benzene levels was followed, and was found to influence atmospheric concentrations over a wide geographical area. An evaluation of the relationship between VOCs and meteorological parameters identified the impact of photo-oxidation and air mass mixing on average atmospheric concentrations. PMID- 11785641 TI - Application of an integrated prepstation-GC-NPD system to automated continuous measurement of formaldehyde and acetaldehyde in the atmosphere. AB - An integrated PrepStation-gas chromatography-nitrogen phosphorus detection (GC NPD) system was used for the fully automated, continuous, low parts per billion analysis of lower aldehydes in the atmosphere. Analysis involved a solid phase extraction procedure based on the collection of aldehydes from air pumped through a silica gel cartridge impregnated with acidified 2,4-dinitrophenylhydrazine (DNPH). Automated continuous measurements were performed with a typical temporal resolution of 3 h, including 146 min for sampling of air at a constant air flow rate of 0.15 L min(-1) and 34 min for the preparation and extraction of several cartridges. Analysis of samples could be performed in parallel by using previously defined scheduler settings from separate, independent software to operate the PrepStation module. GC-NPD measurements were highly repeatable, and relative standard deviations were < 3.0%. Recoveries for all compounds were 88 101%. DNPH decomposition products did not adversely affect the quantitative determination of aldehyde DNPHs; therefore, it was not necessary to remove excess DNPH reagent. The limits of quantification (10sigma of the blank hydrazones) of formaldehyde and acetaldehyde were 2.2 and 1.2 ppb, respectively, for 21.9 L (0.15 L min(-1) for 146 min) of air sample volume. The integrated PrepStation GC NPD system gave results comparable to those of the Sep-Pak DNPH silica cartridge method. PMID- 11785642 TI - Sampling and analysis of gaseous pollutants and related particulate matter in a Mediterranean site: Antalya-Turkey. AB - Gas phase pollutants. nitric acid (HNO3), sulfur dioxide (SO2), ammonia (NH3) and particulate matter, were collected simultaneously for six months from the Eastern Mediterranean atmosphere (Kucuk Calticak, Antalya) using a "filter pack" system developed in our laboratory. This system is a combination of chemically treated filters for the collection of gaseous ammonia and sulfur dioxide. and Teflon and nylon filters for the collection of particulate matter and gaseous nitric acid, respectively. After pre-treatment, Teflon, nylon and the treated filters were analyzed by ion chromatography (IC) for major ionic species: SO4(2-) NO3- and Cl, and by colorimetry for NH4+ ion. Comparison of the SRM (Standard Reference Material) results with measured concentrations showed a good precision for the IC analyses: 3%, 1% and 2% for Cl-, NO3 and SO4(2-) ions. respectively. Most of the measured parameters were log-normally distributed. Chloride ion had the highest (4.30 microg m(-3) and HNO3 had the lowest (0.42 microg m(-3)) concentrations. Total acidity in the Eastern Mediterranean is controlled by 47.7% HNO3 and 52.8% by H2SO4. Ammonium, nss-SO4(2-) (non-sea salt sulfate) and NO3 did not show a strong correlation, (r = 0.4), which means that ammonia is not the major neutralizing species in the Eastern Mediterranean atmosphere. PMID- 11785643 TI - Use of rosaniline hydrochloride dye for atmospheric SO2 determination and method sensitivity analysis. AB - The para-rosaniline hydrochloride (PRA) dye-based manual method (P. W. West and G. C. Gaeke, Anal. Chem., 1956, 28, 1816) is widely used for sulfur dioxide measurements in the atmosphere, particularly in developing countries. In this investigation, the properties of a less costly, rosaniline hydrochloride (RA) dye were found to be similar to those of the PRA dye, and showed no significant variation in atmospheric SO2 determination. Furthermore, the sensitivity of various operational parameters to slight changes similar to those encountered during normal use in the different stages of monitoring, namely sample collection and chemical analysis, was evaluated using both dyes, and the deviations in the method response from the reference parameter value were quantified. The method was found to be highly sensitive to the amount of reagent (HCHO and dye) addition in SO2 exposed samples for colorimetric determination. Therefore, utmost care is required in the preparation of reagents and in the addition of the appropriate amount of reagents during chemical analysis in order to obtain the actual concentrations of SO2 in the atmosphere. PMID- 11785644 TI - Estimation of wet, dry and bulk deposition of atmospheric nitrogen in Connecticut. AB - Atmospheric nitrogen species including NO3-, NH4+ and total nitrogen in air and precipitation samples were collected with low-volume filter packs and wet deposition collectors from March 1999 through the end of December 2000 in seven sampling locations in Connecticut. Three sampling locations were chosen along the shores of Long Island Sound and four were chosen in interior sections of Connecticut. Sampling sites were chosen to represent both rural and urban sectors. Wet deposition flux of nitrogen species was calculated using wet concentrations, the volume of collected precipitation and the opening surface area of the Aerochemetrics wet deposition collector. The dry deposition flux of nitrogen species was estimated with the application of the dry deposition inferential model (DDIM). Bulk deposition of nitrogen was collected with the aid of a device based on the Swedish IVL Sampler. The dry deposition fluxes of NO3-, NH4+ and total nitrogen were found to be significantly higher in urban areas than the rural sampling locations. There was, however, no significant difference between the wet deposition fluxes of different nitrogen species in rural and urban sampling locations. When inland and coastal sites were compared, the dry deposition fluxes of NH4+ and total nitrogen were significantly higher in inland locations and there was no significant difference between coastal and inland sampling locations for wet deposition fluxes of nitrogen species. No significant difference was observed between the bulk deposition and the sum of the wet and dry deposition fluxes of total nitrogen at rural sampling locations. In urban sampling locations, the bulk deposition flux of total nitrogen was significantly lower than the sum of dry and wet deposition fluxes. There appears to be a similar seasonal trend in wet and dry deposition fluxes of total nitrogen in Connecticut with high and low deposition fluxes occurring in summer and winter periods, respectively. PMID- 11785645 TI - Speciation of nickel in airborne particulate matter by means of sequential extraction in a micro flow system and determination by graphite furnace atomic absorption spectrometry and inductively coupled plasma mass spectrometry. AB - A four-stage sequential extraction procedure for the speciation of nickel has been applied to ambient aerosol samples. The determination of the soluble, sulfidic, metallic and oxidic Ni fractions in particulate matter was carried out by graphite furnace (electrothermal) atomic absorption spectrometry (ETAAS) and inductively coupled plasma mass spectrometry (ICP-MS). An EDTA solution, a mixture of diammonium citrate and hydrogen peroxide, and a KCuCl3 solution were used as leaching agents for the determination of the soluble, sulfidic and metallic species, respectively, and nitric acid was used for the determination of oxidic compounds after microwave digestion of particulate matter sampled on filters. A new micro scale filter holder placed in a closed flow injection analysis (FIA) system for use in nickel speciation by means of sequential extraction, and the results of the optimisation of the extraction conditions are described. The temperature program for ETAAS was optimised for all extraction solutions with the aid of temperature curves. Pyrolysis temperatures of 900. 600 and 1,000 degrees C were found to be optimum for EDTA, hydrogen peroxide plus ammonium citrate and KCuCl3-containing solutions, respectively. Airborne dust was sampled on lilters at two locations near to a metallurgical plant in Dortmund, Germany. Concentrations in the low ng m(-3) range down to the detections limits (0.1-0.3 ng m(-3)) and various nickel species were found to be present in the collected dust. The mean fractions of total nickel (sampling period of one month) were found to contain 36+20% of soluble, 6 +/- 4% of sulfidic, 11 +/- 15% of metallic and 48 +/- 18% of oxidic nickel. PMID- 11785646 TI - 85Kr measurement system for continuous monitoring at the Meteorological Research Institute, Japan. AB - A 85Kr measurement system for continuous monitoring based principally on the BfS IAR method (activity measurement of 85Kr by gas counting coupled with gas chromatographic separation, using pure CH4 as carrier and Counting gas) was implemented for the first time in Japan. In this paper, a detailed description of the system and procedures is given and the inter-comparison results of our system with the BfS-IAR system are presented. A consistent temporal concentration change with high accuracy and consistency of the respective data with the BfS-IAR data (maximum difference of 5%) were achieved with the Meteorological Research Institute (MRI) system, which shows that the system is valid and reliable for the purpose of background monitoring for 85Kr in air. Also, the 85Kr monitoring record at the MRI during 1995-2001 is described. The record distinctively shows the Northern Hemispheric background 85Kr concentrations at the mid-latitude and the elevated concentrations affected by the operation of a nuclear fuel reprocessing plant in Tokai-mura, Ibaraki. Japan. PMID- 11785647 TI - Kinetic study of 2-nitrophenol photodegradation on Al-pillared montmorillonite doped with copper. AB - This work concerns the kinetic study of heterogeneous photocatalytic processes on copper adsorbed on aluminium-pillared montmorillonite. Photomineralization of 2 nitrophenol in aqueous medium was investigated as a function of the following experimental parameters: initial concentration of pollutant, light intensity, initial concentration of hydroperoxide, catalyst concentration, pH and temperature. The kinetic expression obtained can be described by the formula: V(NP) = k(0)exp(-Ea/RT)I(beta) x (K(NP)[NP]K(H2O2)[H2O2]/ [1+K(NP)[NP]0)(1+K(H2O2)[H2O2])] The apparent overall activation energy obtained for 2-nitrophenol was 28 kJ mol(-1). By fitting the above equation with the experimental data and values for beta (1.94), K(H2O2) (32.291 mol(-1)) and K(NP) (47.25 x 10(2)l mol(-1)), the kinetic equation can predict the concentration of 2 nitrophenol during the entire degradation process at pH 5 and a catalyst concentration of 0.5 g l(-1). PMID- 11785649 TI - Pesticides in perspective. Organic agriculture: development and state of the art. PMID- 11785648 TI - Elevated dentine-lead levels in deciduous teeth collected from remote first nation communities located in the western James Bay region of northern Ontario, Canada. AB - Teeth were collected from First Nation schoolchildren inhabiting the remote western James Bay region of northern Ontario, Canada. Lead levels in dentine chips were determined by graphite furnace atomic absorption spectrometry, for naturally exfoliated deciduous teeth. Within exfoliated teeth (one tooth supplied per person), no significant differences in lead concentrations between tooth type were found (P = 0.36). The mean lead concentration of exfoliated teeth of 9.2 microg g(-1) dry weight (N = 61) from this remote region was comparable to levels reported by others for children inhabiting urban centers or residing near smelters. Further, 24.6% (N = 15) had elevated dentine-lead levels ( > 10 microg g(-1)). Lead levels in soil, water, and air have been reported as being low and unimportant sources of exposure for people of the western James Bay area. Evidence is reviewed suggesting that lead contaminated game meat was one source of environmental lead exposure. Consumption data indicate that wildlife is still an important food source for First Nation people of the western James Bay region; 98% (46/47) of the children surveyed consumed some type of wild meat. PMID- 11785650 TI - HIV prevention for indigenous people of the Amazon basin. AB - This study identifies theoretically-based predictors of condom use in a sample of 251 sexually active adults recruited from Sao Gabriel da Cachoeira and six indigneous communities of the Upper Rio Negro region of Amazonas Brazil. The information-motivation-behavioral skills (IMB) model of AIDS-preventive behavior was used to describe the roles of HIV/AIDS knowledge, experiences with and attitudes toward condom use, peer influences, perceived vulnerability, monogamy and behavioral skills. A predictive path analytic model revealed significant predictors of more condom use including male gender, greater sexual HIV knowledge, positive experiences and attitudes about condom use, multiple partners, and greater behavioral skills. Results suggest that attention to behavioral skills for negotiating safer sex and instruction in the correct use of condoms are important elements in reducing high risk behaviors. Increasing the specific knowledge level of indigenous people regarding the complexities of sexual transmission of HIV is crucial and should be addressed. Heightening individuals' understanding of the limited protection of serial monogamy, and the need to conduct gender-specific training for behavior change to reduce transmission of HIV should be an additional goal of Brazilian health professionals. Obstacles to the implementation of the IMB HIV prevention program in Amazonas are noted and an alternative Brazilian HIV/AIDS prevention program is discussed. PMID- 11785651 TI - HCV genotype analysis in HCV-HIV-co-infected Puerto Ricans who are injecting drug users: undetermined and mixed infections. AB - Direct percutaneous exposure is the main route of HCV transmission. In Puerto Rico half of people infected with HIV use illicit drugs. The effects of HCV in the course of HIV infection and vice versa have been extensively studied, but remain highly controversial. This may be due to HCV genetic heterogeneity. Therefore, a complex classification into genotypes has emerged that prompted us to determined how this impacts a population of intravenous drug users (IDUs) co infected with HIV-1. Using Inno-LiPa II technique, we analyzed samples from 171 HCV-HIV-1-co-infected IDUs and 375 from a general HCV population of unknown HIV or source of infection status. Similar HCV genotype distribution was detected in these populations. HCV genotype 1a was the most frequently in IDUs-co-infected with HIV-1, followed by 1b and 3a. Twenty mixed infections and 5 undetermined genotypes were reported. A reduced HCV viral load was observed in HIV-1 positives with wasting syndrome. Individuals with a high HIV-1 viral load presented a low HCV viral load. There were no correlation between HCV genotypes and AIDS-related event. Patients with genotype 1b showed a higher HCV viral load. Males presented higher HCV viral load than females. Females were predominantly affected by genotype 1a, and men by 1a and 1b. Neither the HCV viral load nor the frequency of genotypes were influenced by the antiretroviral modality. The importance of continuous genotype monitoring is stressed. PMID- 11785652 TI - Her-2/neu oncogene expression in Puerto Rican females with breast cancer. AB - Her-2/neu belongs to the family of tyrosine kinase transmembrane proteins whose overexpression has been associated with a poor prognosis in patients with breast cancer. The product of this proto-oncogene is overexpressed in 25-30% of human breast cancer and is the target of selective immunotherapy. Concerned about the ethnic differences on the expression of this oncogene, we have evaluated 143 consecutive specimens of primary breast cancer diagnosed in San Pablo Hospital, Puerto Rico. The specimens were analyzed for Her-2/neu expression using immunohistochemistry assays (Hercept test). We have related the expression of hormone receptor status, percent cells in S phase, DNA ploidy, tumor size, nodal status and menopausal state with the Her2/neu expression. Out of 143 specimens, 28 overexpressed the Her-2/neu (19.6%). Of the Her/2 negative 30/114 (26%) were estrogen receptor negative as compared to 9/27 (33%) (p = 0.464). The degree of aneuploidy was abnormal in 25/104 (24%) in the Her-2/neu negative vs 11/27 (41%) p = 0.083. The percent cell in DNA synthesis was high in 16/77 (21%) in Her-2/neu negative vs 4/15 (27%) p = 0.613. The tumor size was greater than 2 cm in 35/106 (33%) in Her-2/neu negative vs 9/23 (39%) p = 0.575. In the progesterone specimens negative for Her2, 44/114 (39%) were Her2/neu negative vs 15/27 (56%) p = 0.108. No differences were seen regarding menopausal status, age and nuclear grading. A trend favoring abnormal aneuploidy in Her2/neu positive was seen. Nodal involvement was significantly associated with Her2/neu overexpression. (p = 0.037). Although the incidence of Her2 overexpression found in this database was somewhat lower than the one reported in the literature, this might also be due to the small cohort examined or to the technique utilized. PMID- 11785653 TI - Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer. AB - The actin cytoskeleton is the key cellular machinery responsible for cellular movement. Changes in the organization and distribution of actin and actin binding protein are necessary for several cellular processes such as focal adhesion formation, cell motility and cell invasion. Here we examined differences in cytoskeletal protein distribution, cell morphometry and cell motility of metastatic and non-metastatic cells. Correlations were found between metastatic potential phenotypic properties such as cell motility, cell spreading and cytoskeletal organization in prostate cancer. As a cell progresses from a normal state to a malignant state, it loses its ability to function normally and also become poorly differentiated. Differentiation therapy is concerned with the redirection of malignant cells toward a terminal, non-dividing state using non cytotoxic agents. Two well acknowledged differentiation agents, retinoic acid (RA) and diflouromethylomithine (DFMO) were examined for their ability to alter cellular phenotypes associated with metastatic potential in rat prostate cancer cell lines. The results of these studies indicate that there are sub-cellular differences between non-metastatic and highly metastatic cells relative to cytoskeletal organization. We also show that treatment of highly metastatic cells with either RA or DFMO significantly alters cell morphology, cell morphometry and motility to states similar to non-metastatic cells. PMID- 11785655 TI - The fluorescence study of the binding of zinc phthalocyanine to breast cancer cells solubilized in synthetic liposomes. AB - Steady state fluorescence spectroscopy is used to study the binding characteristics of zinc phthalocyanine (ZnPc) to MCF-7 human breast cancer cells solubilized in a liposomal vesicle prepared with L-alpha-phosphatidic acid, dipalmitoyl. The observed apparent binding constant, K', of 1.14 x 10(7) together with the free energy of binding, deltaG, of -40.38 kJ/mole suggests a very strong affinity and spontaneous binding between the breast cancer cells and ZnPc. The wavelength of excitation of ZnPc in the liposomal vesicle (611 nm) is favorable to cytotoxic reactive singlet oxygen (1O2*) production necessary for photooxygenation reaction with the cancerous cells and is within the energy threshold that has good penetration to normal tissues without undue skin necrosis. PMID- 11785654 TI - Novel antineoplastic isochalcones inhibit the expression of cyclooxygenase 1,2 and EGF in human prostate cancer cell line LNCaP. AB - Experiments were conducted to determine the effects of novel anti-neoplastic isochalcones (DJ compounds), on cyclooxyegenase 1 and 2 (COX-1 and COX-2) enzyme expression in androgen receptor dependent human prostate cancer cell line LNCaP. Results from Western blot analysis and cell flow cytometry showed that DJ52 and DJ53 decreased the steady state levels of COX-1 and COX-2 protein levels in a dose dependent manner. In addition, DJ52 and DJ53 decreased the levels of epidermal growth factor (EGF) in LNCaP cells. In this study, we report that novel isochalcones decreased COX-1, COX-2 and EGF levels as well as LNCaP cellular growth in a dose responsive manner. Our findings indicate that relative decreases in COX-1, COX-2 and EGF expressions might serve as indicators of tumor growth inhibition in prostate neoplasms. PMID- 11785656 TI - Effects of oxidized low density lipoprotein on nitric oxide synthetase and protein kinase C activities in bovine endothelial cells. AB - Oxidized low-density lipoprotein (Ox-LDL) is an atherogenic lipoprotein. It has been suggested that Ox-LDL causes endothelial dysfunction by decreasing the release of endothelium-derived factors (EDRF-NO) or increasing the inactivation of EDRF-NO. The mechanism by which Ox-LDL causes dysfunctional NO during early stages of atherosclerosis is not clear. The purpose of this study was to examine the role of Ox-LDL on nitric oxide synthetase (eNOS), protein kinase C (PKC) activities and cAMP production in bovine aortic endothelial cells (BAEC). Ox-LDL stimulated PKC activity of BAEC but it inhibited both eNOS activity and cAMP production. Ox-LDL partially inhibited the forskolin stimulated cAMP production. Furthermore, we observed that 8Br-cAMP treatment decreased the activity of eNOS in a concentration dependent manner. Serotonin which has a profound inhibitory effect on cAMP production also stimulated eNOS activity. Pertusis toxin treatment blocked the stimulatory action of serotonin on the stimulation of eNOS activity. Our results thus suggest that Ox-LDL inhibit the endothelium-dependent relaxation. One possible mechanism is that Ox-LDL stimulates PKC activity, which in turn increases the phosphorylation of the Gi-protein. Inhibition of Gi-protein then leads to reduced release of NO from endothelial cells and thus causes endothelial dysfunction. PMID- 11785657 TI - Protein kinase C inhibits insulin-induced Akt activation in vascular smooth muscle cells. AB - Protein kinase C (PKC) activation, enhanced by hyperglycemia, is associated with many tissue abnormalities observed in diabetes. Akt is a serine/threonine kinase that mediates various biological responses induced by insulin. We hypothesized that the negative regulation of Akt in the vasculature by PKC could contribute to insulin resistant states and, may therefore play a role in the pathogenesis of cardiovascular disease. In this study, we specifically looked at the ability of PKC to inhibit Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells (VSMCs). Activation of Akt was determined by immunoblotting with a phospho-Akt antibody that selectively recognizes Ser473 phosphorylated Akt. A PKC activator, phorbol 12-myristate 13-acetate (PMA), inhibited insulin dependent Akt phosphorylation. However, PMA did not inhibit platelet-derived growth factor (PDGF)-induced activation of Akt. We further showed that the PKC inhibitor, G06983, blocked the PMA-induced inhibition of Akt phosphorylation by insulin. In addition, we demonstrated that PMA inhibited the insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). From these data, we conclude that PKC is a potent negative regulator of the insulin signal in the vasculature, which indicate an important role of PKC in the development of insulin resistance in cardiovascular disease. PMID- 11785658 TI - Cardiac autonomic function in Blacks with congestive heart failure: vagomimetic action, alteration in sympathovagal balance, and the effect of ACE inhibition on central and peripheral vagal tone. AB - Cardiac autonomic dysfunction is common in heart disease with or without congestive heart failure, and can cause sudden cardiac death. However, cardiac autonomic abnormalities in non-ischemic (hypertensive) heart failure, which is prevalent in Black Africans is poorly documented. We conducted a cross-sectional study of 32 patients with congestive heart failure, mostly secondary to hypertension (aged 52 +/- 15 years, with ejection fraction of 0.38 +/- 11) and 30 age- and sex-matched healthy volunteers (aged 51 +/- 11 years, 14 males/16 females). Cardiac autonomic function was assessed by the Valsalva's maneuver, respiratory sinus arrhythmia (for cardiac vagal tone) and the pressor and chronotropic changes following forearm isometric handgrip exercise and the assumption of upright posture (tests of sympathetic function). The exercise tolerance of the cardiac patients was assessed by the distance covered during 6 min of walking. The Valsalva ratio was significantly lower in chronic heart failure, 1.10 +/- 0.08 compared to the healthy controls 1.47 +/- 0.20 (p<0.001). Specifically, the phase IV bradycardia in heart failure, was significantly attenuated to 650 +/- 121 msec compared to the value of 935 +/- 101 msec in healthy controls (p<0.001). The phase 11 Valsalva tachycardia did not differ between the patients and controls. The respiratory sinus arrhythmia was also significantly reduced in chronic heart failure (p<0.05) compared to controls. Treatment of the heart failure patients with enalapril-digoxin and diuretics by 4 weeks, resulted in a reversal of the autonomic abnormalities. The phase IV bradycardia increased significantly to 798 +/- 164 msec (p<0.01) and the Valsalva ratio to 1.35 +/- 0.25 (p<0.01) and the respiratory sinus arrhythmia increased toward normal. There was close positive correlation between the Valsalva's ratio and the 6 min self paced distance covered (r = 0.44, p = 0.03 ANOVA), and a weak inverse correlation to cardiac size and cardiothoracic ratio (r = -0.31, p = 0.09). This study demonstrates cardiac autonomic dysfunction (especially reduced vagal tone) in Black Nigerians with mainly non-ischemic congestive heart failure. The parasympathetic dysfunction significantly correlates with severity of heart failure. Current treatment reverses autonomic dysfunction to values seen in healthy age matched controls, mainly through augmentation of cardiac parasympathetic activity. PMID- 11785659 TI - Effects of gamma-2-melanocyte-stimulating hormone on protein kinase C activity and expression in spontaneous hypertensive rats (SHR). AB - Administration of gamma-2-melanocyte stimulating hormone (gamma-2-MSH) to rats increases blood pressure, heart rate and natriuresis by acting through the nervous system and this response is more pronounced in spontaneous hypertensive rat (SHR). The molecular mechanisms underlying these effects are unknown, however, protein kinase C (PKC) activity is higher in SHR tissues and melanocortins are known to activate the phosphoinositide (PI) signaling pathway. In this study, we tested the hypothesis that gamma-2-MSH potentiation of PKC activation is increased in nerve terminals from SHR brain. Synaptosomes were isolated from SHR and age-matched control Wistar Kyoto (WKY) rats and incubated with gamma-2-MSH. Total particulate-fraction associated PKC activity was determined and the expression of individual isozymes analyzed by immunoblotting. Treatment with gamma-2-MSH resulted in an increase in particulate-associated PKC activity in hindbrain synaptosomes that was more prominent in SHR. The levels of membrane-associated PKC-alpha and beta-isozymes were considerably less than for PKC-gamma in these tissues as determined by immunoblotting. The novel PKC isozymes delta and epsilon were detected in total synaptosomes but not in membrane fractions. These data suggest that PKC-gamma is the major presynaptic PKC isozyme and that PKC may be an important mediator for gamma-2-MSH in neural tissues. PMID- 11785660 TI - Expression and distribution of protein kinase C isozymes in brain tissue of spontaneous hypertensive rats. AB - Hypertension activates many endocrine, neuroendocrine and metabolic responses. How hypertension alters these functions remains unknown. Consequently the pathophysiology of hypertension related illnesses are incompletely understood. Protein kinase C (PKC) isoforms play an important role in cellular signal transduction and altered PKC activity has been reported in spontaneous hypertensive rats (SHR). In order to understand the role that PKC plays in hypertension, we hypothesized that PKC activity is significantly expressed in synaptosomal preparations from the brains of SHRs. In addition, the neuroanatomical distribution of this expression was mapped and compared to control animals. The brains were further studied for signs of neuropathology. Total PKC activity was significantly increased in synaptosomal samples isolated from the forebrain, midbrain, and hindbrain of SHR rats. Westem blot analysis identified PKC-alpha, -beta, -gamma, -delta, -epsilon and -zeta in all brain regions. Immunohistochemical analyses indicated that PKC-gamma was localized in cell bodies and processes in many autonomic cardiovascular control regions. These results suggest that PKC may be an important modulator of autonomic blood pressure control. PMID- 11785663 TI - Healthy people 2010. Proceedings of the 7th RCMI (Research Centers in Minority Institutions) International Symposium on Health Disparities. November 12-15, 2000. San Juan, Puerto Rico. PMID- 11785661 TI - Sex differences in cocaine-induced behavioral sensitization. AB - To further understand how sex differences affect the development and maintenance of sensitization, 48 adult Fischer rats (24 female and 24 male) received chronic administration (14 days) of cocaine (15 mg/kg, i.p.) or saline or a challenge dose (7 days after chronic cocaine administration). Sex differences were observed in the development and maintenance of cocaine-induced total locomotor, ambulatory and rearing activity. Although, overall cocaine administration increased stereotypic activity in both male and female rats, female rats had significantly higher stereotypic activity than male rats across the three behavioral test days (1, 7 and 14). Female rats had statistically significant higher benzoylecognine levels after acute cocaine administration than male rats. However, no differences between male and female rats in benzoylecognine plasma levels were observed after chronic and challenge doses of cocaine administration. Interestingly, after acute and challenge cocaine administration, corticosterone levels were significantly higher in female rats when compared to male rats. This study confirms previous reports that there are sex differences in the behavioral response to cocaine. Moreover, this study expands previous studies by demonstrating that sex differences occur in only certain aspects of cocaine-induced behavioral activation and the development and maintenance of cocaine-induced behavioral sensitization. PMID- 11785664 TI - Sequence analysis of HIV-1 insertion sites in peripheral blood lymphocytes. AB - An essential component of the HIV-1 life cycle involves insertion in the genome of an infected cell. The site of HIV-1 integration has the potential to disrupt a gene and perturb a normal cellular function. To begin to address whether disease pathogenesis may correlate with the site of insertion, flanking cellular sequences at these HIV integrated regions were directly amplified from peripheral blood mononuclear cells DNA from a broad range of infected individuals using an inverse polymerase chain reaction strategy. Amplified flanking regions were sequenced and examined for similarity to the nucleic acid database. In this group of analyzed samples, the HIV-1 provirus was inserted within non-coding regions throughout the genome of the infected host, in which 7/14 sites were positioned in close proximity to different Alu repetitive elements while 2/14 sites were located within intron sequences. Insertions were also detected at sites without a specific gene designation but not within short tandem repetitive sequences, telomeres or centromeric repeat regions. Altogether, it is expected that this approach will yield new information on sites of integration by HIV-1 that may be associated with the pathogenic manifestations of disease progression. PMID- 11785665 TI - Antibiotic resistant N. gonorrhoeae in Trinidad and Tobago. AB - We tested the susceptibility patterns of 128 N. gonorrhoeae isolates to six antimicrobials; penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin and azithromycin, and examined whether certain demographic or behavioral factors related to antibiotic use increased the likelihood of infection by a resistant strain. There was a low rate of resistance to penicillin; penicillinase-producing and chromosomal-mediated penicillin resistant gonorrhea were estimated to be 0.8%. A much higher proportion of isolates were resistant to tetracycline (up to 15%). All isolates were sensitive to spectinomycin, ciprofloxacin and ceftriaxone. However, less than 2% of isolates displayed intermediate resistance to both ciprofloxacin and ceftriaxone, and 9% exhibited intermediate resistance to spectinomycin. Patients who had obtained medication before attending the clinic and had taken all of the medication were more likely (p = 0.03) to be infected with a resistant strain of gonococcus. Also, patients who were asked by a clinic doctor to return for a test of cure during an earlier clinic visit, but who did not return were more likely to be infected with a resistant organism (p = 0.006) compared to those who returned at the doctor's request. These findings have important implications for antibiotic use and educational programs in Trinidad and Tobago. PMID- 11785666 TI - Neutralization/enhancement of macrophage-tropic SIVmac infection by plasma from macaques infected with macrophage-tropic or lymphocyte-tropic SIVmac. AB - Plasma from macaques inoculated with macrophage-tropic SIVmac were tested for neutralization/enhancement of macrophage-tropic SIVmac239-17EBR in normal rhesus macrophages. The plasma of a macaque (R71) that developed a highly virulent neuro tropic (macrophage-tropic) strain of SIVmac in neuro-adaptation studies significantly enhanced infection of SIVmac239-17EBR as well as infection of dual tropic SIVmac251. Plasma from other macaques that were inoculated with macrophage tropic virus, neutralized SIVmac239-17EBR. Also, plasma from macaques infected with lymphocyte-tropic SIVmac239 or dual-tropic SIVmac251 neutralized SIVmac251 infection. When the effect of R71 plasma on the early stages of the SIV life cycle was investigated, this plasma significantly increased binding of 35S methionine labeled SIVmac239-17EBR and increased binding of 35S-SIVmac251 to primary macrophages, unlike plasma from other macaques infected with either macrophage-tropic or lymphocyte-tropic SIV. A single-cycle infection assay showed higher percentages of positive cells and more intense fluorescence in cultures treated with R71 plasma compared with control plasma. By in situ hybridization, SIV RNA transcripts were detected earlier (12 hr post-infection) and in higher percentages, in cultures treated with R71 plasma than in cultures treated with control plasma (18 hr post-infection). These results indicate that enhancing activity in infected macaque plasma may be associated with severe infection by highly virulent macrophage-tropic (neuro-tropic) SIV. The enhancing effect occurs early in infection and results in increased transcription of SIV RNA. PMID- 11785667 TI - Role of Bruton's tyrosine kinase in B cell development. AB - X-linked agammaglobulinemia (XLA) is one of the most frequent inherited immunodeficiency diseases in man and is characterized by an almost complete arrest of B cell differentiation at the pre-B cell stage. The gene defective in XLA encodes the cytoplasmic signaling molecule Bruton's tyrosine kinase (Btk). Next to the CBA/N strain of mice, carrying a single amino acid substitution mutation in the Btk gene, which results in the X-linked immunodeficiency (xid) phenotype, additional mouse models have been developed to study the role of Btk in vivo. This review discusses the analyses of Btk null-mutants, obtained by gene targeting in embryonic stem cells, and transgenic mice that express wild-type or mutated forms of the Btk gene. These studies provided information on the function of Btk at several important checkpoints throughout B cell development. Analyses of the mouse models indicated that Btk is not essential for pre-B cell receptor signaling in the mouse. By contrast, Btk-mediated B cell receptor signaling appears to be required for the survival of immature B cells in the bone marrow, that have performed a successful immunoglobulin (Ig) L chain locus rearrangement, resulting in the expression of a non-autoreactive Ig on the membrane. Btk is also shown to be involved in signaling pathways that govern the development of peripheral B cells, including follicular entry, follicular maturation and plasma cell differentiation. PMID- 11785668 TI - Incidence of apoptosis in the lymphoid organs of normal or malaria infected mice is decreased in CD18 and urokinase-receptor (UPAR, CD87) deficient mice. AB - Incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, CD18 -/- and urokinase receptor (uPAR, CD87) -/- mice, untreated or Plasmodium Berghei Anka (PbA) infected. In non infected mice, incidence of apoptosis was lower in the lymph nodes of CD18 -/- and uPAR -/- than in +/+ mice, as seen by FACS analysis to count the number of hypodiploid and Annexin-V binding cells. Infection of mice with PbA resulted in a marked increase in the size of spleen and lymph nodes 7-8 days after infection, which was slightly higher in uPAR -/- and CD 18 -/- than in +/+ mice. PbA infection increased about 7 fold the incidence of apoptosis in the lymphoid organs of +/+, especially in the white pulp and germinal centers of the spleen and lymph nodes, while in contrast it was unchanged in PbA infected CD 18 -/- or uPAR -/- mice. Serum IgG levels, and number of circulating leukocytes were significantly higher in both uPAR and CD18 /- than in +/+ mice. These results indicate that the CD18 and uPAR surface molecules, which are known to be associated in the cell membrane, have an important influence upon the incidence of cell survival in both normal or stimulated lymphoid organs. PMID- 11785669 TI - Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats. AB - Dark Agouti (DA) rats are highly susceptible to induction of Th-1-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulated in vitro produce significantly more Interferon gamma (IFN-gamma) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO x DA) F1 rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+ cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-gamma and TNF-alpha production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-beta leads to exceptional susceptibility to EAE in DA rats. PMID- 11785670 TI - Induction of germinal centers by MMTV encoded superantigen on B cells. AB - It has not been established whether an endogenous superantigen (SAg) expressed on B cells can induce germinal centers (GCs). An interesting model is that of mammary tumor virus encoded viral SAgs, which induce vigorous T cell proliferation and are predominantly expressed on activated B cells. We have used this model to analyze the possibility that direct stimulation of Mtv7+ DBA/2 B cells by vSAg-responsive (Vbeta6+) BALB/c T cells can give rise to GCs. Injection of BALB/c SCID mice i.v. with 2 x 10(6) DBA/2 B cells, together with LPS, followed by 2 x 10(6) BALB/c T cells induces numerous large splenic GCs within 3 5 days. The GCs are still large on day 7, but are very much reduced by day 10. B cell activation with LPS is needed for this effect. These GCs form in spite of the apparent absence of follicular dendritic cells (FDCs) as judged by staining for several FDC surface markers. Control mice receiving either BALB/c T or DBA/2 B cells + LPS alone or DBA/2 T + B cells + LPS fail to exhibit any GCs on days 3 7. Numerous small clusters of PNA+ cells, but few large GCs are observed when TNF R(p55)-Ig is also injected, whereas LTbetaR-Ig treatment impeded the formation of aggregations of these cells even further, leaving scattered PNA+ single cells and very small clumps throughout the white pulp of the spleens. Anti-TNFalpha had no effect. These results suggest that endogenous vSAg mediated GC formation is independent of antigen trapping by FDCs. PMID- 11785671 TI - Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes. AB - Xanthine derivative, pentoxifylline (PTX), has been recently shown to exert a protective effects in certain animal models of autoimmunity, including diabetes in NOD mice. In the present study, the immunomodulatory potential of PTX was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-SZ) in genetically susceptible CBA/H mice (tested with 40 mg SZ/kg b.w. for 5 days) and DA rats (tested with 20 mg/kg b.w. for 5 days). In both species, 2-3 weeks following the MLD-SZ treatment, sustained hyperglycemia developed, as an outcome of inflammatory reaction with endothelial cell activation and accumulation of mononuclear cells. Although there was no evidence of typical insulitis in early disease development (day 10), in both rats and mice, macrophages, CD4+ and CD8+ cells were present in the islets of Langerhans as diffuse mononuclear infiltrates with the expression of IFN-gamma, and inducible NO synthase (iNOS). Administration of PTX (200 mg/kg/day for 10 days) in combination with MLD-SZ reduced insulitis and the production of mediators tested, and prevented the development of hyperglycemia. These results suggest that beneficial effects of PTX involve down-regulation of local proinflammatory cytokine-mediated NO synthase pathway. They also demonstrate that in addition to ameliorating spontaneous autoimmunity in NOD mice, PTX may be effective in downregulating an inflammatory autoimmune process triggered in susceptible host by an external agents, such as streptozotocin. PMID- 11785672 TI - Enforced expression of Bcl-2 selectively perturbs negative selection of dual reactive antibodies. AB - We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA ("dual reactive" antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation. PMID- 11785673 TI - Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. AB - In naturally and experimentally occurring scrapie in sheep, prions invade the immune system and replicate in lymphoid organs. Here we analysed immunohistochemically, in seven spleens of 6-month-old healthy sheep, the nature of the cells expressing prion protein (PrP) potentially supporting prion replication, as well as their relationship with autonomic innervation. PrP was identified using either RB1 rabbit antiserum or 4F2 monoclonal antibody directed against AA 108-123 portion of the bovine and AA 79-92 of human prion protein respectively. Using double labelling analysis, we demonstrated that PrPc is expressed by follicular dendritic cells using a specific monoclonal antibody (CNA42). We also showed the close vicinity of these PrP expressing cells with noradrenergic fibers, using a polyclonal tyrosine hydroxylase antibody. Our results may help the study of the cellular requirements for the possible neuroinvasion from the spleen. PMID- 11785674 TI - T cell mediated antibody invariance in an immune response against a bacterial carbohydrate antigen requires CD28/B7-1 costimulation. AB - The humoral immune response against alpha(1-->3) dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype-specific regulatory T cells recognizing in association with I-Ed and in cognate T/B interaction the VH CDR3 derived peptide of the J558 idiotpye. Only B-2 lymphocytes produce IgG whereas B 1 cells do not participate in the production of this Ig class. Using a novel synthetic all alpha(1-->3)-D-gluco configurated tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bgamma memory cells and supports previous by adoptive transfer experiments. In this suppression an involvement of CD28/B7-1 interaction can be demonstrated which is a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Ed interaction between J558 Id-specific T cells and J558 idiotype bearing B cells. This results in an activation of 178-4 Ts cells, leading to an overall suppression of the Dex specific IgG isotype production on the one hand and on the other hand provides a signal for the survival and clonal expansion of J558 Id-positive B cells. PMID- 11785675 TI - Human FDC express PrPc in vivo and in vitro. AB - Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormal prion protein (protease-resistant prion, PrPres). PrPres accumulation is also detected in lymphoid organs after peripheral infection. Several studies suggest that follicular dendritic cells (FDC) could be the site of PrPres retention and amplification. Here we show that human follicular dendritic cells can express normal cellular prion protein (PrPc) both in situ and in vitro. When tonsillar cryosections were treated with anti-PrP antibody, the label was found on some very delicate cell extensions inside the lymphoid follicles, especially in the germinal centres. These extensions react with DRC1 antibody, used frequently to label FDC. Other structures labelled with anti-PrP antibody were the keratinocytes. To confirm the ability of FDC to synthesise PrPc, we isolated FDC by a non-enzymatic procedure and cultured them. By cytochemistry and flow cytometry it was clearly shown that FDC do produce PrPc. PMID- 11785676 TI - Characterization of the rapid proteolytic shedding of murine L-selectin. AB - The structural requirements for L-selectin shedding were studied in murine leukocytes. Upon activation, L-selectin on both lymphocytes and neutrophils undergoes cleavage by a membrane metalloprotease, resulting in the generation of a soluble ectodomain and a membrane-retained 6 kD fragment. Radiochemical sequencing demonstrated a cleavage site in the membrane-proximal region (MPR) between R321 and S322, which is homologous to the human site. Although intact neutrophil L-selectin is larger, it is cleaved at the same, or very close, site. Analysis of several transfectants expressing L-selectin point mutations and chimeric constructs suggest that, like human shedding, the proteolytic process has relatively loose sequence specificity for the substrate site. In addition, some constructs are susceptible to slow constitutive cleavage, but their shedding does not increase upon PMA stimulation, showing that basal and activated shedding are separable processes. Insertion of the 15 amino acid MPR into murine B7.2 conferred upon this molecule susceptibility to constitutive shedding. PMA stimulation results in little or no acceleration of down regulation of this molecule. These results suggest that recognition of both the membrane-proximal cleavage site and of a site distant from the MPR are required for maximal induction of L-selectin shedding. PMID- 11785677 TI - Evidence for distinct mechanisms in the shaping of the CD4 T cell repertoire in histologically distinct myasthenia gravis-associated thymomas. AB - The major histocompatibility complex (MHC) class II is involved both in thymocyte maturation and peptide presentation and might thus play a key role in the pathogenesis of paraneoplastic myasthenia gravis (MG) in thymomas. To further investigate this issue, we analyzed and scored the expression of epithelial class II expression in 35 thymomas (medullary, MDT; mixed, MXT; cortical and well differentiated thymic carcinoma, CT/WDTC) and correlated it with the histological tumor subtype, prevalence of MG and thymocyte maturation, which was analyzed by flow cytometry and RT-PCR. Our results show that both MHC class II expression and thymocyte maturation are highly dependent on the histological tumor subtype. CT/WDTC retain features of the normal outer thymic cortex, namely substantial MHC class II expression together with normal early thymocyte maturation until late phases of positive selection, but disturbed terminal thymopoiesis. By contrast, MDT and MXT retain features of the normal inner cortex and the medulla with low to absent class II expression and highly abnormal early thymocyte maturation including impaired positive selection, while terminal T cell maturation in MXT appeared undisturbed. There was no correlation between MHC class II expression and MG status for a given tumor subtype. In conclusion, our results provide evidence for a different histogenesis of cortical thymomas and well differentiated carcinomas on the one hand and mixed and medullary thymomas on the other. Decreased expression levels of MHC class II, although of crucial importance for abnormal intratumorous maturation, are not sufficient to explain the emergence of paraneoplastic MG. PMID- 11785678 TI - Studies on prion replication in spleen. AB - Some of the early events following scrapie infection take place in the lymphoreticular system (LRS) and result in significant replication of prions in lymphoid organs. The identity of the cells in the LRS that produce prions and their role in neuroinvasion are still unknown. We find that in the spleen of scrapie-infected mice, prions are associated with T and B cells and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDC's); curiously, no infectivity was found in lymphocytes from blood of the same mice. Thus, splenic lymphocytes either replicate prions or acquire them from another source. Studies on PrP knockout mice with ectopic expression of PrP restricted to only B or T lymphocytes suggest that neither of these by themselves are competent for prion replication. To determine whether B and T cells are able to pick up prions from other sources, irradiated wild-type mice were reconstituted with PrP-deficient lymphohaematopoietic stem cells. Following intraperitoneal inoculation of these mice, no infectivity was found on splenic lymphocytes whereas the stroma (comprising the radiation-resistant, PrP expressing FDC's) contained prions. These results imply that splenic lymphocytes can acquire prions, possibly from FDC's, but only if they express PrP. PMID- 11785679 TI - Differential effects of male and female gonadal hormones on the intrathymic T cell maturation. AB - The study was undertaken to further elucidate a role of gonadal hormones in maintenance of normal thymocyte maturation and sexual dimorphism in the intrathymic T-cell development. Rats of both sexes were gonadectomized or sham gonadectomized (controls) at age of 2 and 6 months, and 30 days later the thymus size, cellularity and thymocyte composition were evaluated. In both control and gonadectomized rats, in spite of age, sexual dimorphism in the thymus size and cellularity was found. Gonadectomy in 2-month-old rats of both sexes increased the thymus cellularity, volumes of both cortex and medulla and thymus size (to a less extent in males), while in 6-month-old rats, in this respect, it was effective only in females. In ovariectomized (OVX) rats the increase in volume of cortex was more marked in younger rats, while that of medulla did not differ between rats of different age. It seems obvious that in both groups of OVX rats the volume of medullary non-lymphoid component was enlarged (the increase in medullary volume was more pronounced than that in its cellularity). Unlikely, in rats orchidectomized (ORX) at age of 2 months the volume of this component was either decreased or unaltered (the increase in the volume of medulla was less conspicuous than that in the number of medullary thymocytes). In control and gonadectomized rats of both ages, sexual dimorphism in the composition of thymocyte subsets was also observed. Gonadectomy in 2-month-old rats affected distinct stages of thymocyte maturation in male (increased the relative proportions of CD4+8+TCR alphabeta(low) cells and their CD4-8+TCR alphabeta(low) precursors and decreased those of the most mature CD4+8-TCR alphabeta(high) and CD4-8+TCR alphabeta(high) cells) and female rats (decreased only the percentage of the least mature CD4-8-TCR alphabeta- cells). In older rats only ovariectomy had impact on the relative proportion of thymocytes decreasing, besides the relative proportion of CD4-8-TCR alphabeta- cells, those of CD4-8+TCR alphabeta-, CD4-8+TCR alphabeta(low), positively selected CD4+8+TCR alphabeta(high) and the most mature CD4+8-TCR alphabeta(high), CD4-8+TCR alphabeta(high) cells and exerting an opposite effect on the percentages of CD4+8+TCR alphabeta- and CD4+8+TCR alphabeta(low) cells. Thus, results showed sex- and age-dependent changes in sensitivity of both the developing thymocytes and non-lymphoid cells to long-lasting gonadal deprivation. PMID- 11785680 TI - Prolactin and prolactin receptor expression in rat, small intestine, intraepithelial lymphocytes during neonatal development. AB - Intraepithelial lymphocytes (IEL) are specialized T cells found between the epithelial cells of the small intestine. Because of their location, IEL are the first lymphocytes to contact intestinal bacteria and food antigens. In the neonate, IEL may be the first cells of the immune system to interact with milk borne hormones including prolactin (PRL). PRL, an endocrine hormone abundant in breast milk, interacts with cells through surface receptors. PRL has been shown to function as an immunoregulator and may affect the development of the newborn's immune system. To determine if PRL plays a role in IEL development, small intestine IEL from rats of various ages were examined for the presence of surface prolactin receptor (PRL-R) and several lymphoid markers by flow cytometry. Between birth and 96 days of age about 80% of IEL were found to express PRL-R. These same cells also expressed the mRNA for PRL. Additionally, all of the IEL subpopulations examined were found to express PRL-R. Analysis of the normal development of rat IEL revealed an age related increase in total IEL, CD4 positive cells as well as a peak in interleukin-2 receptor (IL-2R) expression at weaning. In summary, the results indicate that IEL express PRL and PRL-R. In addition, an activation marker, IL-2R, changes in expression during neonatal development. PMID- 11785681 TI - Bioavailability and bioequivalence: an FDA regulatory overview. AB - Bioavailability and/or bioequivalence studies play a key role in the drug development period for both new drug products and their generic equivalents. For both, these studies are also important in the postapproval period in the presence of certain manufacturing changes. Like many regulatory studies, the assessment of bioavailability and bioequivalence can generally be achieved by considering the following three questions. What is the primary question of the study? What are the tests that can be used to address the question? What degree of confidence is needed for the test outcome? This article reviews the regulatory science of bioavailability and bioequivalence and provides FDA's recommendations for drug sponsors who intend to establish bioavailability and/or demonstrate bioequivalence for their pharmaceutical products during the developmental process or after approval. PMID- 11785682 TI - Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol. AB - PURPOSE: To evaluate the beta2-adrenergic receptor (beta2AR) genotype frequency in the Japanese population and the relationship between beta2AR genotype at amino acid position 16 (beta2AR-16) and desensitization to beta2-agonist ex vivo. METHODS: The beta2AR genotypes at amino acid positions 16, 27, and 164 of 92 healthy Japanese subjects were determined by polymerase chain reaction restriction fragment-length polymorphism. The relationship between the beta2AR-16 genotype and the desensitization to beta2-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50 microg, Meptin) was given orally for 5 days, and peripheral blood was obtained before and after 5 days of consecutive medications followed by the assessment of the intracellular cAMP levels in peripheral blood mononuclear cells after incubation with or without procaterol hydrochloride (0-1000 ng/mL). RESULTS: Allele frequency was Arg16:Gly16 = 46%:54%, Gln27: Glu27 = 92%:8%, and Thr164:Ile164 = 100%:0%, respectively. The cAMP levels were increased by incubation with procaterol hydrochloride, and the increase was suppressed after 5 days of consecutive medications. The suppression was more significant in the homozygote for Gly16 than the homozygote for Arg16. CONCLUSIONS: The desensitization to beta2-agonist was associated more frequently with the mutation at beta2AR-16 (Gly16). PMID- 11785683 TI - Telomere amount and length assay. AB - PURPOSE: Telomeres are specific DNA structure at the ends of chromosomes to protect chromosomes from fusion, recombination, and degradation. Telomere length changes are implicated in cell senescence, aging, tumorigenesis, and DNA repair. The standard method for measuring telomere length is Southern blot analysis. This method has several disadvantages, i.e., loss of DNA during membrane blotting, high background due to nonspecific binding of telomere probe to membrane, and loss of telomeric signal due to extensive washing. These limitations resulted in a low signal-to-noise ratio and, therefore, reduced sensitivity and reproducibility. The multi-step Southern blot is also highly labor-intensive. The present study was to develop a more quantitative assay of telomeric amount and length (TALA). METHODS: TALA was based on solution hybridization and did not require blotting, prehybridization, and washing. The major steps were (a) DNA preparation and digestion with restriction endonucleases, (b) hybridization between DNA and telomeric probe, (c) agarose gel electrophoresis, and (d) autoradiography and data analysis. RESULTS: The telomere amount measured by TALA was linearly correlated with the amount of DNA analyzed (r2 = 0.985, P < 0.01). The telomere length measured by TALA also correlated with the telomere length determined by fluorescence in situ hybridization (r2 = 0.99, P < 0.01). Compared to the Southern blot analysis, TALA showed a 4-fold greater sensitivity, 4.6-fold higher signal-to-noise ratio, >2 fold-higher reproducibility, and 4-fold less time requirement. CONCLUSION: We report here a rapid, sensitive, and quantitative assay for measuring telomere length and amount. PMID- 11785684 TI - Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P glycoprotein. AB - PURPOSE: MDR1 P-glycoprotein (P-gp) plays an important role in determining drug disposition. The purpose of the present study was to establish in vitro models to predict the in vivo function of P-gp. METHODS: As an in vitro method, the transcellular transport of 12 compounds across the monolayer of Caco-2- and MDR1 transfected cells was examined. The ability of these compounds to stimulate the ATP hydrolysis was also determined using the isolated membrane fraction expressing P-gp. As a parameter to describe the in vivo P-gp function, we calculated the brain-to-plasma concentration ratio of compounds in mdr1a/1b knockout mice divided by the same ratio in wild type mice. RESULTS: A good correlation was observed between the in vitro flux ratio across the monolayer and in vivo P-gp function for 12 compounds. Although all compounds that stimulated ATP hydrolysis were significantly transported by P-gp, some compounds were transported by P-gp without significantly affecting ATP hydrolysis. CONCLUSION: Collectively, the in vitro flux ratio across monolayers of P-gp-expressing cells may be used to predict in vivo P-gp function. The extent of ATP-hydrolysis in vitro may also be a useful parameter for in vivo prediction, particularly for eliminating P-gp substrates in high-throughput screening procedures. PMID- 11785685 TI - MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. AB - PURPOSE: The aim of this study was to characterize L-lactic acid transport using a conditionally immortalized rat retinal capillary endothelial cell line (TR iBRB2) as a model of in vitro inner blood-retinal barrier (iBRB) to obtain a better understanding of the transport mechanism at the iBRB. METHODS: TR-iBRB2 cells were cultured at 33 degrees C, and L-lactic acid uptake was monitored by measuring [14C]L-lactic acid at 37 degrees C. The expression and mRNA level of monocarboxylate transporter (MCT)1 and MCT2 were determined by reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time RT PCR with specific primers, respectively. RESULTS: The [14C]L-lactic acid uptake by TR-iBRB2 cells increased up to a pH of 5.0 and was inhibited in the presence of 10 mM L-lactic acid. The [14C]L-lactic acid uptake at pH 6.0 was both temperature- and concentration-dependent with a Michaelis-Menten constant of 1.7 mM and a maximum uptake rate of 15 nmol/(30 s mg of protein). This process was reduced by carbonylcyanide p-trifluoromethoxyphenylhydrazone (protonophore), alpha-cyano-4-hydroxycinnamate, and p-chloromercuribenzenesulfonate (typical inhibitors for H+-coupled monocarboxylic acid transport), suggesting that L lactic acid uptake by TR-iBRB2 cells is a carrier-mediated transport process coupled with an H+ gradient. [14C]L-Lactic acid uptake was markedly inhibited by monocarboxylic acids but not dicarboxylic acids and amino acids. Moreover, salicylic and valproic acids competitively inhibited this process with an inhibition constant of 4.7 mM and 5.4 mM, respectively. Although MCT1 and MCT2 mRNA were found to be expressed in TR-iBRB2 cells, MCT1 mRNA was found to be present at a concentration 33-fold greater than that of MCT2 mRNA using quantitative real-time PCR. [14C]L-Lactic acid was significantly reduced by 5 (N,N-hexamethylene)-amiloride at pH 7.4 and Na+/H+ exchanger I mRNA was expressed in TR-iBRB2 cells. CONCLUSION: L-Lactic acid transport at the iBRB is an H coupled and carrier-mediated mechanism via MCT1 that is competitively inhibited by monocarboxylate drugs. PMID- 11785686 TI - Facilitation of pulmonary insulin absorption by H-MAP: pharmacokinetics and pharmacodynamics in rats. AB - PURPOSE: Several low molecular weight amino acids have previously been reported to enable the oral delivery of proteins. In the present studies, the effect of H MAP (hydroxy methyl amino propionic acid) on the pharmacokinetics (PK) and pharmacodynamics (PD) of porcine insulin delivered to the lungs of rats by spray instillation (SI) has been determined. METHODS: Aliquots (100 microl) of increasing doses of porcine insulin alone (0.26, 1.3, 2.6, 13, and 26 U/kg) or combined with increasing doses of H-MAP (5, 10, 16, and 25 mg/kg), at pH 7.2-7.6 were administered intratracheally to fasted anesthetized rats using a micro spray instillator. Blood samples were collected from the jugular vein at specified intervals and the plasma concentrations of insulin and glucose were determined. The PK and PD of porcine insulin alone following subcutaneous (SC) administration of increasing doses were also determined. RESULTS: The PK of insulin administered either by SI to the lungs or SC injection were absorption rate dependent, resulting in post-peak half-lives 10 to 25-fold greater than the reported intravenous elimination half-life (3 min). The relative bioavailability (F') of insulin administered alone by SI varied from 23.8 to 80% for the lowest and highest insulin dose, respectively. Co-administration of H-MAP and insulin to the lungs significantly changed the PK and PD of insulin in a dose dependent fashion. Maximum PK and PD responses were obtained at an H-MAP dose of 16 mg/kg and an insulin dose of 1.3 U/kg. At this combination, the relative bioavailability of insulin was increased more than 2.5 fold, maximum concentration (Cmax) increased 2-fold and the minimum plasma glucose concentration (%MPGC) was reduced more than 2-fold with respect to same dose of insulin alone. A greater total reduction in plasma glucose (%TRPG0-->t) was achieved for H-MAP/insulin combination (66+/-5%) compared to insulin alone (47+/-10 %). CONCLUSION: H-MAP has potential for increasing the pulmonary bioavailability of insulin administered through the lungs. PMID- 11785687 TI - Immediate and short-term cellular and biochemical responses to pulmonary single dose studies of insulin and H-MAP. AB - PURPOSE: It was previously reported that co-administration of H-MAP to the airways of the lungs significantly influenced the absorption, disposition. and effect of insulin in a dose-dependent fashion. Doses of H-MAP (16 mg/kg) and insulin (1.3 U/kg) required to achieve maximum pharmacokinetic and pharmacodynamic responses were determined. The purpose of the present study was to evaluate the effects of insulin and H-MAP spray-instilled (SI) to rats on the physiology of the lung. A short-term, single-dose study of insulin alone and combined with H-MAP was performed. METHODS: Solutions of either insulin (INS), H MAP, or insulin plus H-MAP (INMA) were SI to the lungs of rats. Lipopolysaccharide solution (LPS) and sodium dodecyl sulfate solution (SDS) were used as positive controls. and normal saline (SAL) was used as negative control. Animals were sacrificed at various time points and bronchoalveolar lavage (BAL) was conducted. BAL fluid was analyzed for local markers of lung injury, such as total cell numbers, differential cell count, total protein content and enzyme activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and N acetyl glucosaminidase (NAG). RESULTS: SI of any solution, including normal saline, seems to have a minor but detectable effect on the normal physiology of the lung. SI of positive control solutions resulted in most markers of immunity and lung injury being significantly elevated, notably enzyme activity and white cell infiltrate. In contrast, SI of INS produced a response similar to that of SAL. SI of INMA resulted in a small transient response characterized by a slight increase in the proportion of neutrophils at 24 h, which decreased with time and was comparable to that of SAL at 72 PMID- 11785688 TI - Frequency dependence of sonophoresis. AB - PURPOSE: Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we sought to determine the dependence of low frequency sonophoresis on ultrasound frequency, intensity and energy density. METHODS: Pig skin was exposed to low-frequency ultrasound over a range of ultrasound frequency and intensity conditions. The degree of skin permeabilization was measured using its conductivity. Imaging experiments were also carried out to visualize the transport pathways created by ultrasound. RESULTS: The data showed that for each frequency (in the range of 19.6-93.4 kHz), there exists a threshold intensity below which no detectable conductivity enhancement was observed. The threshold intensity increased with frequency. It is feasible to achieve the desired conductivity (permeability) enhancement regardless of the choice of frequency, although the necessary energy density is higher at higher frequencies. Low frequencies (approximately 20 kHz) induced localized transport compared to a more dispersed effect seen with higher frequencies (approximately 58.9 kHz). CONCLUSIONS: This study provides a quantitative understanding of the effects of low-frequency ultrasound on skin permeability. PMID- 11785689 TI - Contributions of electromigration and electroosmosis to iontophoretic drug delivery. AB - PURPOSE: To determine the electromigration and electroosmotic contributions to the iontophoretic delivery of lidocaine hydrochloride, in addition to the more lipophilic quinine and propranolol hydrochlorides, in the presence and absence of background electrolyte. METHODS: In vitro experiments, using excised pig ear skin and both vertical and side-by-side diffusion cells, were performed as a function of drug concentration and with and without background electrolytes in the anodal formulation. Concomitantly, the contribution of electroosmosis in each experimental configuration was monitored by following the transport of the neutral, polar marker molecule, mannitol. RESULTS: Electromigration was the dominant mechanism of drug iontophoresis (typically representing approximately 90% of the total flux). In the presence of background electrolyte, lidocaine delivery increased linearly with concentration as it competed more and more effectively with Na+ to carry the charge across the skin. However, iontophoretic delivery of quinine and propranolol increased non-linearly with concentration. Without electrolytes, on the other hand, electrotransport of the three drugs was essentially independent of concentration over the range 1-100 mM. Transport efficiency of lidocaine was approximately 10%, whereas that of the more lipophilic compounds was significanly less, with the major charge carrier being Cl- moving from beneath the skin into the anodal chamber. Both quinine and propranolol induced a concentration-dependent attenuation of electroosmotic flow in the normal anode-to-cathode direction. CONCLUSION: Dissecting apart the mechanistic contributions to iontophoretic drug delivery is key to the optimization of the formulation, and to the efficient use of the drug substance. PMID- 11785690 TI - Optimizing iontophoretic drug delivery: identification and distribution of the charge-carrying species. AB - PURPOSE: To identify and quantify, in vitro and in vivo (in humans), the charge carrying species during transdermal iontophoresis of lidocaine hydrochloride as a function of the concentration of drug relative to that of sodium chloride in the anodal solution. METHODS: In vitro experiments in standard diffusion cells quantified lidocaine delivery and the outward migration of chloride across the skin. Electrotransport of Na+ was inferred by difference, allowing transport numbers of the three main charge-carrying species to be deduced. In vivo, outward electrotransport of Cl- was measured and compared to the corresponding in vitro results. RESULTS: The transport number of lidocaine increased linearly with increasing mole fraction and reached 0.15-0.20 at X(L) = 1.0. In the absence of Na+, most of the charge was carried by Cl- (>80%) despite the skin retaining its net negative charge and cation permselectivity. In vivo data correlated very well with in vitro results. CONCLUSIONS: The mole faction of drug (relative to competing ions of like polarity) is the crucial determinant of the extent to which it can carry charge across the skin during iontophoresis. The outward electromigration of Cl-, in the sense opposite to drug delivery, may offer a useful means by which to optimize iontophoretic efficiency in the absence of competing cations in the anode formulation. PMID- 11785691 TI - Iontophoretic delivery of ropinirole hydrochloride: effect of current density and vehicle formulation. AB - PURPOSE: The objectives of this work were 1) to establish the feasibility of the transdermal iontophoretic delivery of ropinirole hydrochloride; 2) to investigate the possibility of delivering therapeutic doses of this drug; and 3) to determine the key factors that control ropinirole electrotransport. METHODS: A series of in vitro transdermal iontophoretic experiments were instituted to study the effects of drug concentration, co-ion concentration, intensity of current, and application time on ropinirole flux. The convective contribution to ropinirole electrotransport was evaluated by following the transport of the electroosmotic marker mannitol. RESULTS: Ropinirole flux decreased dramatically in the presence of competing ions. This effect was observed even when the molar fraction of the two competing cations was kept constant. Anodal flux of mannitol decreased with drug concentration, indicating a possible alteration of the skin permselectivity. In the absence of competing co-ions, ropinirole transport number reached a maximum value (8-13%). In these conditions, the main factor controlling drug delivery was the intensity of current applied. CONCLUSIONS: Transdermal iontophoresis allowed the delivery of therapeutic doses of ropinirole. The dose administered and the input rate were controlled by the judicious choice of the key delivery factors here described. PMID- 11785692 TI - Differentiation of gut and hepatic first-pass effect of drugs: 1. Studies of verapamil in ported dogs. AB - PURPOSE: To investigate the relative contributions of the gut and liver to the first-pass loss of verapamil (VL) using an in vivo intestinal-vascular access port (IVAP) dog model. METHODS: Basic pharmacokinetics of VL were determined after intravenous (IV: 0.5 mg/kg), portal venous (PV: 2 mg/kg), and duodenal (ID: 2 mg/kg) administration in IVAP dogs. Serial blood samples were collected for 8 h after dosing, and plasma was analyzed for unchanged drug by a high-performance liquid chromatography-fluorescence method. Extraction ratios in the liver and intestinal tract were determined from the area under the concentration-time curves for ID, PV, and IV administration. The functional role of CYP450 or secretory transporters such as P-gp on the gut and liver first-pass loss of VL was further studied using ritonavir, a known substrate or inhibitor of these processes. RESULTS: The liver had a high intrinsic capacity for clearing VL because the absolute bioavailability (BA) of VL was 21.7% after PV administration. The BA of VL after ID administration was 23.5%; therefore, intestinal absorption was complete and intestinal extraction was negligible (ER(GI) approximately 0). The BA of VL increased from 23.5% to 66.2% in the presence of ritonavir primarily due to a reduction in hepatic extraction. CONCLUSIONS: Although the liver had a high intrinsic capacity for extracting VL, the contribution of gut to the first-pass loss of VL was negligible. Because of the additive effects of intestinal CYP3A-mediated metabolism and secretory transport, a significant gut first-pass effect was expected, but not observed in dogs. These studies demonstrate the utility of the in vivo IVAP dog model for evaluating the relative contribution of the gut and liver to the first-pass loss of drugs and for characterizing the functional role that CYP450 metabolism and/or secretory transporters play in drug-drug interactions and reduced oral bioavailability. PMID- 11785693 TI - Predictive ability of level A in vitro-in vivo correlation for ringcap controlled release acetaminophen tablets. AB - PURPOSE: The goal of this study was to establish and validate an in vitro-in vivo correlation (IVIVC) for two sustained-release formulations (i.e., a matrix tablet and a RingCap banded matrix tablet) containing 750 mg of acetaminophen. METHODS: The in vitro dissolution and in vivo disposition of these formulations were examined by using a USP type III dissolution apparatus and a single-dose, three way, crossover study that included an immediate-release acetaminophen dosage form, respectively. An IVIVC was established by using the mean fraction dissolved (FD) and mean fraction absorbed (FA) and used to simulate the plasma concentration-time profile of acetaminophen after administration of the matrix tablet (i.e., internal validation) and RingCap banded matrix tablet (i.e., external validation). RESULTS: A statistically significant relationship (r2 = 0.997, P < 0.001) existed between the FD and FA for matrix tablets and was best described by the equation (FA) = 0.984 x (FD) + 0.0133. The percent predictions errors in CMAX and AUCL were <10% when predicting the plasma concentration-time profiles for the two formulations, validating the internal and external predictability of the IVIVC. CONCLUSIONS: The data (i) show that in vitro dissolution data are a good predictor of in vivo fraction absorbed for acetaminophen, (ii) support the general use of in vitro dissolution data for readily soluble and readily absorbed drugs, (iii) suggest that acetaminophen may serve as a model drug for evaluating novel sustained-release delivery systems, and (iv) provide a tangible example of the limitations of current methods for predicting and validating IVIVC. PMID- 11785694 TI - In vitro intestinal permeability of factor Xa inhibitors: influence of chemical structure on passive transport and susceptibility to efflux. AB - PURPOSE: To study the in vitro intestinal permeability of a number of newly synthesised factor Xa inhibitors to better understand the poor oral absorption of these compounds. METHODS: The bidirectional transport of the fXa inhibitors was studied in the Caco-2 cell model and isolated rat ileal tissue. An attempt was made to characterize efflux mechanisms with the help of commonly used substrates and inhibitors of various transport proteins. In addition, the transport of the fXa inhibitors was studied in MDCK cells transfected with the human MDR1 gene and expressing large amounts of P-glycoprotein (Pgp). RESULTS: The in vitro absorptive permeability was low for all but one of the fXa inhibitors. For compounds with non-substituted amidine, a charge (due to ionisation at neutral pH) may have resulted in poor membrane partitioning. Neutral compounds with substituted amidines were effluxed from the epithelial cells. The significance of the secretion process was illustrated by the results obtained for a neutral analogue showing high absorptive Caco-2 cell permeability that was not obviated by efflux. Transport inhibition studies in Caco-2 and permeability studies in the MDR1-transfected MDCK cells consistently showed that Pgp is not involved in the secretion of fXa inhibitors. Besides efflux, metabolic liability limited the permeation of the neutral lipophilic analogues with a carbamate ester. CONCLUSIONS: Poor intestinal permeability may be an important factor in the incomplete oral absorption of the bisbenzimidazole-type fXa inhibitors. Poor permeability may be related to poor membrane partitioning for hydrophilic analogues, whereas susceptibility to efflux transports and gastro-intestinal enzymatic degradation may limit the permeability of some of the neutral less hydrophilic derivatives. PMID- 11785695 TI - Enhanced bioavailability of calcitonin formulated with alkylglycosides following nasal and ocular administration in rats. AB - PURPOSE: The purpose of this study was to characterize the effects of alkylglycosides on the bioavailability of calcitonin following nasal and ocular administration. METHODS: A salmon calcitonin specific radioimmunoassay kit was used to measure calcitonin levels in anesthetized rats at various times after nasal or ocular administration of calcitonin formulated with saline or with octylmaltoside, a medium chain length alkylglycoside or tetradecylmaltoside, a long chain alkylglycoside. The extent of calcitonin absorption was determined directly from the plasma calcitonin level-time curve and the bioavailability of calcitonin was determined from the area under the plasma calcium level-time curve. The calcium level was determined using a colorimetric method. RESULTS: When the nasal formulation contained calcitonin plus saline or 0.125% octylmaltoside, little or no calcitonin was absorbed. However, plasma calcitonin levels were increased and plasma calcium levels were decreased when the nasal formulation contained calcitonin plus 0.125% or 0.25% tetradecylmaltoside. Maximal calcitonin levels were observed 7.5-10 min after nasal administration of the formulation. Ocular administration of calcitonin formulated with tetradecylmaltoside also resulted in calcitonin absorption, but less calcitonin absorption was found after ocular administration than after nasal administration. CONCLUSION: The experimental data indicate that tetradecylmaltoside, but not octylmaltoside. can be effectively used to enhance the bioavailability of nasally and ocularly administered calcitonin. PMID- 11785696 TI - Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix. AB - PURPOSE: The purpose of this study was to develop a polymeric sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2) and to evaluate local bone growth induced by the sustained release of BMP-2 in an animal model. METHODS: BMP-2 was incorporated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres to obtain different release rates. Two sustained and an immediate release implants were produced by suspending the BMP-2 loaded PLGA microspheres in aqueous sodium carboxymethylcellulose (CMC), lyophilizing, and cutting the dried materials to the size of the animal bone defects. The local in vivo release at the implantation site in rat calvarial defects was determined by gamma scintigraphy using radiolabeled BMP-2. The local bone induction in the critical size of rabbit calvarial defects was evaluated six weeks post implantation. RESULTS: The immediate release implant showed about 65% initial drug release within 24 h and the remaining BMP-2 quickly exhausted from the implantation site within 7 days. The sustained release implants, showing 45-55% initial release followed by a prolonged release for 21 days, released a greater amount of BMP-2 at the implantation site and maintained higher serum BMP-2 for the longer period of time compared to the immediate release implant. Significant bone growth was observed in all BMP-2 treated defects while the defects without treatment or with BMP-2-free implant showed minimal bone healing. 75-79% of rabbit calvarial defect area was healed with newly induced bone matrix by the sustained release implants in 6 weeks as compared to 45% recovery from the immediate release implant. CONCLUSION: The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model. PMID- 11785697 TI - In situ study of insulin aggregation induced by water-organic solvent interface. AB - PURPOSE: The aim of this study was to assess insulin stability by monitoring in situ time-course of insulin aggregation induced by a water-organic solvent (o/w) interface that occurs during the microencapsulation process. METHODS: Insulin aggregation at a simple o/w interface was monitored spectrophotometrically by detecting the percentage of turbidity changes (%T) at 350 nm. The effects of protein concentration and agitation and the presence of poly (lactic-co-glycolic acid) (PLGA) in methylene chloride (MC) on insulin aggregation were observed. For the 0.72 mg/ml insulin in phosphate-buffered saline (PBS), the effect of nonionic (dodecyl maltoside [DDM]) and anionic (sodium dodecyl sulfate [SDS]) surfactant in PBS were also evaluated at various protein/surfactant mol ratios. The conformation of insulin protected by a 10-fold molar excess of SDS recovered after 1 h of contact with MC was evaluated via circular dichroism (CD) spectroscopy. RESULTS: A typical turbidity-time profile was represented by a sigmoidal curve. Greater change in %T was observed with increasing insulin concentration, in the presence of PLGA in MC and in the presence of agitation. DDM failed to delay insulin aggregation at all ratios used, whereas a less than 10% change in %T was observed in 1 h when a 10- - approximately 20-fold excess of SDS was used. CD spectra indicated that the presence of insulin in SDS after 1 h of contact with MC qualitatively retained its secondary structure integrity. CONCLUSIONS: An experimental method was designed for an in situ assessment of protein stability at the o/w interface. PMID- 11785698 TI - Predicting plasticization efficiency from three-dimensional molecular structure of a polymer plasticizer. AB - PURPOSE: In polymeric coatings, plasticizers are used to improve the film-forming characteristic of the polymers. In this study, a computerized method (VolSurf with GRID) was used as a novel tool for the prediction plasticization efficiency (beta) of test compounds, and for determining the critical molecular properties needed for polymer plasticization. METHODS: The film-former, starch acetate DS 2.8 (SA), was plasticized with each of 24 tested compounds. A decrease in glass transition temperature of the plasticized free films (determined by differential scanning calorimeter (DSC)) was used as an indicator for beta. Partial least squares discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of the plasticizers. RESULTS: A good correlation (r2 = 0.77, q2 = 0.58) between the molecular modeling results and the experimental data demonstrated that beta can be predicted from the three dimensional molecular structure of a compound. Favorable structural properties identified for the potent SA plasticizer were strong hydrogen bonding capacity and a definitive hydrophobic region on the molecule. CONCLUSIONS: The VolSurf method is a valuable tool for predicting the plasticization efficiency of a compound. The correlation between experimental and calculated glass transition temperature values verifies that physicochemical properties are primary factors influencing plasticization efficiency of a compound. PMID- 11785699 TI - Molecular mobility and fragility in indomethacin: a thermally stimulated depolarization current study. AB - PURPOSE: To show that thermally stimulated depolarization currents (TSDC), which is a dielectric experimental technique relatively unknown in the pharmaceutical scientists community, is a powerful technique to study molecular mobility in pharmaceutical solids, below their glass transition temperature (Tg). Indomethacin (Tg = 42 degrees C) is used as a model compound. METHODS: TSDC is used to isolate the individual modes of motion present in indomethacin, in the temperature range between -165 degrees C and +60 degrees C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in indomethacin. RESULTS: Two different relaxational processes were detected and characterized: the glass transition relaxation, or alpha-process, and a sub-Tg relaxation, or secondary process. The lower temperature secondary process presents a very low intensity, a very low activation energy, and a very low degree of cooperativity. The fragility index (Angell's scale) of indomethacin obtained from TSDC data is m = 64, which can be compared with other values reported in the literature and obtained from other experimental techniques. CONCLUSIONS: TSDC data indicate that indomethacin is a relatively strong glass former (fragility similar to glycerol but lower than sorbitol, trehalose, and sucrose). The high-resolution power of the TSDC technique is illustrated by the fact that it detected and characterized the secondary relaxation in indomethacin, which was not possible by other techniques. PMID- 11785701 TI - Multilamellar liposomes and solid-supported lipid membranes (TRANSIL): screening of lipid-water partitioning toward a high-throughput scale. AB - PURPOSE: Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated. METHODS: Drugs were incubated at pH 7.4 with egg yolk lecithin membranes either on a solid support (TRANSIL beads) or in the form of multilamellar liposomes. Phase separation of lipid and water phase was achieved by ultracentrifugation in case of liposomes or by a short filtration step in case of solid-supported lipid membranes. RESULTS: Lipid-water partitioning data of both approaches correlate well without systematic deviations in the investigated lipophilicity range. The solid-supported lipid membrane approach provides high-precision data in an automated microwell-plate setup. The lipid composition of the solid-supported lipid membranes was varied to study the influence of membrane change on lipid-water partitioning. In addition, pH dependent measurements have been performed with minimal experimental effort. CONCLUSIONS: Solid-supported lipid membranes represent a valuable tool to determine physiologically relevant lipid-water partitioning data of pharmaceuticals in an automated setup and is well suited for high-throughput data generation in lead optimization programs. PMID- 11785700 TI - In vitro and in vivo properties of recombinant human serum albumin from Pichia pastoris purified by a method of short processing time. AB - PURPOSE: Recombinant human serum albumin (rHSA), secreted by a Pichia pastoris expression system, was purified by a fast and efficient method, the essential feature of which is strong but reversible binding of the protein to Blue Sepharose. The structural characteristics, stability, and ligand-binding properties of the resulting protein were examined, and pre-clinical studies were performed. METHODS: Protein structure was investigated by amino acid sequencing, sodium polyacrylamide gel electrophoresis, CD spectroscopy and chromatography. Stability was examined by denaturation by guanidine hydrochloride and by calorimetry, and ligand binding was studied by ultrafiltration. Rat experiments were performed with 125I-labeled albumin. RESULTS: Far-ultraviolet and near ultraviolet CD spectra of rHSA were identical to those of human serum albumin isolated from serum (HSA). Mercaptalbumin and non-mercaptalbumin were separated by high-performance liquid chromatography using an N-methylpyridinium polymer based column. 60% of rHSA existed as mercaptalbumin, a content that is higher than that of a commercial preparation of HSA. Fatty acids, N-acetyl-L-tryptophan and pasteurization had similar effects on the conformational stability of rHSA and HSA. Stereoselective ligand-binding properties (warfarin, phenprocoumon, pranoprofen and ibuprofen) of rHSA were the same as those of HSA. The effect of the neutral to base transition on warfarin (site I-ligand) and dansylsarcosine (site II-ligand) binding to rHSA was also similar to HSA. In vivo studies showed comparable half-lives, excretion and tissue distributions of the two albumin preparations. CONCLUSION: The present yeast expression system and purification procedure result in rHSA with structural and functional properties very similar to those of HSA. PMID- 11785703 TI - A simple modified absorption potential. PMID- 11785702 TI - Transdermal delivery of antisense oligonucleotides with microprojection patch (Macroflux) technology. PMID- 11785704 TI - An assessment of reasonable tortuosity values. PMID- 11785705 TI - Evaluation and follow-up of patients with portal hypertension and oesophageal varices: how and when. PMID- 11785706 TI - Treatment of Helicobacter pylori infection unmasks rather than induces symptoms of gastro-oesophageal reflux disease. PMID- 11785707 TI - Intestinal permeability in patients with Crohn's disease and their relatives. PMID- 11785708 TI - IBD: how important are clinical epidemiological studies? PMID- 11785709 TI - EsophaCoil for palliation of dysphagia in unresectable oesophageal carcinoma: short- and long-term results. AB - BACKGROUND AND AIM: Few reports have shown that EsophaCoil is an effective and safe prosthesis for palliation of malignant oesophageal dysphagia. A single centre experience using this type of prosthesis is reported. PATIENTS AND METHODS: Between January 1995 and September 2000, 42 consecutive patients, 41 with unresectable oesophageal cancer and one with oesophageal stenosis secondary to lung cancer, were treated with 44 EsophaCoils (2 patients received 2 stents). Tumours were located in lower third of oesophagus and/or gastric cardia in 22 cases, in middle third in 18 and in upper third in 2. Mean stricture length was 5.3 cm. Implantation was performed on hospitalized patients. RESULTS: EsophaCoil placement was successful all 44 times and was followed by complete expansion of the prostheses. There were no major procedure-related complications or deaths. Dysphagia score improved from mean of 2.9 to 1.3 within 24 hours of stent implantation. Median hospital stay was 2.7 days. Late complications occurred in 14 patients (34.2%): 3 migrations into stomach, 7 tissue overgrowth, 2 late perforations and 2 food impactions. Mean survival time was 4.2 months (range 1 10). CONCLUSIONS: In our experience, full expansion of EsophaCoil was achieved in all cases. This result, was associated with high incidence of retrosternal pain. Relief of dysphagia score was identical to that obtained with other types of Self Expanding Metal Stent. Coil design prevented tumour ingrowth and allowed retrieval of three migrated stents. Mean survival time was similar to that reported in larger series using different types of Self-Expanding Metal Stent. PMID- 11785710 TI - Laparoscopic antireflux surgery in gastro-oesophageal reflux disease patients with concomitant anxiety disorders. AB - BACKGROUND: Several psychological factors are known to affect the subjective outcome, such as quality of life, after laparoscopic antireflux surgery. AIM: To evaluate: a. outcome of laparoscopic antireflux surgery in gastro-oesophageal reflux disease patients with concomitant anxiety disorders, b. potential effects of laparoscopic antireflux surgery on psychiatric comorbidities. PATIENTS AND METHODS: Out of more than 550 patients who underwent laparoscopic antireflux surgery, 21 suffered from additional anxiety disorders. Outcome assessments included traditional data, evaluation of symptoms and side-effects, and quality of life. These data were evaluated before laparoscopic antireflux surgery and 6 weeks, 3 months and 1 year after surgery, RESULTS: Post-operative lower oesophageal sphincter pressure and DeMeester score were normal in all patients. Subjective severity of anxiety disorders remained unchanged in 13 patients 1 year after surgery. One patient suffered from severe dysphagia and required single dilatation. In this patient, severity and frequency of panic attacks increased for approximately 6 months after laparoscopic antireflux surgery. In 7 patients, total relief of panic symptoms was reported within 3 months post-operatively. Severity of most gastro-oesophageal reflux disease-related symptoms decreased significantly after laparoscopic antireflux surgery, but severity of some symptoms remained stable in patients with continuing anxiety disorders. In all patients, Gastrointestinal Quality of Life Index increased significantly. This improvement was less marked in patients with continuing anxiety disorders. Patients presenting total relief of panic symptoms showed an outcome comparable to normal data. CONCLUSIONS: Data obtained suggest that patients with concomitant anxiety disorders should not generally be excluded from laparoscopic antireflux surgery but should be selected more carefully. In these patients, surgery significantly improves quality of life and eliminates gastro-oesophageal reflux disease-related symptoms. Some patients demonstrated less symptomatic relief. In contrast, laparoscopic antireflux surgery was able to eliminate panic disorders in one third of our patients. PMID- 11785711 TI - High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro oesophageal reflux disease after curing Helicobacter pylori infection. AB - BACKGROUND: Gastro-oesophageal reflux disease may develop following eradication of Helicobacter pylori. However gastro-oesophageal reflux disease could be preexistent and misdiagnosed since patients often misinterpret gastro-oesophageal reflux disease symptoms or focus their attention on abdominal symptoms. A questionnaire for analysis of gastro-oesophageal reflux disease symptoms has not been used until now. METHODS: A total of 70 patients with duodenal ulcer and Helicobacter pylori gastritis, without oesophagitis and/or typical gastro oesophageal reflux disease symptoms were studied. All patients received a questionnaire with 5 items focused on abdominal symptoms and 5 on gastro oesophageal reflux disease symptoms. The two symptom scores were calculated separately. After Helicobacter pylori treatment, follow-up consisted of clinical controls every 3 months for 1 year. Patients were asked to describe their complaints and to answer the questionnaire. If gastro-oesophageal reflux disease symptoms recurred endoscopy was performed. RESULTS: At interview, all patients reported a significant improvement in their abdominal symptoms after eradication; however 23 patients (32.8%: group A) reported the occurrence of gastro oesophageal reflux disease symptoms, and 5 of them developed oesophagitis; gastrooesophageal reflux disease symptoms did not appear in the remaining 47 patients (group B). Basal gastro-oesophageal reflux disease score was significantly higher in group A than in group B (1.9+/-1.5 vs 0.9+/-0.9, p<0.005), while the abdominal symptoms score was not different. Following eradication, the score for abdominal symptoms decreased significantly (4.2+/-1.5 vs 1+/-0.8, p<0.0001) in the two groups; conversely, the total gastro-oesophageal reflux disease score remained unchanged, improving in 2 patients in group A and 11 in B, and worsening in 5 in group A and in 1 in B. Presence of hiatus hernia and male sex significantly correlated with the development of reflux symptoms. CONCLUSIONS: Patients who present with gastro-oesophageal reflux disease after Helicobacter pylori eradication are likely to already be affected by gastro oesophageal reflux disease. PMID- 11785712 TI - Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan. AB - BACKGROUND: Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy. AIM: To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin. METHODS: A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction restriction fragment length polymorphism. RESULTS: In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens. CONCLUSION: Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status. PMID- 11785713 TI - Two new treatment regimens for Helicobacter pylori eradication: a randomised study. AB - BACKGROUND: Several studies have found a fairly low Helicobacter pylori eradication rate using a standard 7-day triple therapy in Italy. Recently, two new therapeutic schedules have been proposed with an eradication rate higher than 90%. This study compared the efficacy of these two treatment regimens. PATIENTS AND METHODS: A total of 131 patients with Helicobacter pylori infection and either non-ulcer dyspepsia (73 patients] or peptic ulcer (58 patients) were enrolled. Helicobacter pylori infection was assessed by rapid urease test and histology on gastric biopsies. Patients were randomised to receive either a 5-day course of ranitidine bismuth citrate 400 mg bid, clarithromycin 500 bid, and tinidazole 500 bid, or a 10-day course of omeprazole 20 mg bid plus amoxycillin 1 g bid for the first 5 days, and omeprazole 20 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for the remaining 5 days. Eradication was assessed by endoscopy 4-6 weeks after therapy. RESULTS: Overall, 4 patients (2 for each treatment group) were lost to follow-up. Helicobacter pylori eradication rates were 67.2% (95% confidence interval: 55.7-78.7) and 65.2% (95% confidence interval: 53.7-76.6) at per protocol and intention-to-treat analyses, respectively, after the 5-day regimen, and 96.8% (95% confidence interval: 92.5 100) and 93.8% (95% confidence interval: 88-99.7) after the 10-day regimen (p<0.05). Both treatments were well tolerated, and no major side-effects were reported. CONCLUSIONS: The 5-day regimen gave disappointing results, while the eradication rate after the 10-day regimen was very high. PMID- 11785714 TI - Intestinal permeability in Crohn's disease patients and their first degree relatives. AB - BACKGROUND: Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's disease patients and 26 of their cohabiting first degree relatives were studied. METHODS: To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS: In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohn's disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS: These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohn's disease and their relatives. PMID- 11785715 TI - Survival and causes of death in Italian patients with ulcerative colitis. A GISC nationwide study. AB - BACKGROUND: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease. AIM: To evaluate overall and cause specific mortality rate in a large group of Italian patients with ulcerative colitis. METHODS: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated. RESULTS: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0). CONCLUSIONS: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system. PMID- 11785716 TI - Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study. AB - BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option. PMID- 11785717 TI - Intrahepatic hepatitis C virus replication is increased in patients with regular alcohol consumption. AB - AIMS: To assess clinical significance of liver hepatitis C virus RNA levels and their relationship with epidemiological, biochemical and histological factors. METHODS: A total of 50 patients (mean age 35.5+/-7 years) with biopsy-proven chronic hepatitis C infection were recruited. Risk factors were drug abuse (n=21), transfusion (n=16), other parental routes (n=8; surgery=3, tattooing=5), and idiopathic (n=5). Duration of infection was 16+/-9 years. All patients showed abnormal alanine aminotransferase levels and positive serum hepatitis C virus RNA. Hepatitis C virus genotype was assessed by Inno-Lipa. Liver biopsy was performed for histology and for hepatitis C virus RNA quantification by Amplicor HCV-Monitor Daily alcohol consumption was recorded on two occasions by anamnesis. Inflammation grade was mild (n=31) or severe (n=19). Fibrosis was early stage (n=42) or advanced (n=8). RESULTS: Mean hepatitis C virus RNA levels were 9.4x10(5)+/-1.5x10(6) copies/microg of total RNA in liver tissue, and 9.1x10(5)+/ 1.3x10(6) copies/ml in serum. Viral load in liver was positively correlated with that in serum (r=0.51, p<0.001) and there was a significant relationship between daily alcohol consumption and intrahepatic hepatitis C virus burden (r=0.53; p<0.001). Patients infected with genotype 3a showed lower intrahepatic hepatitis C virus load than patients infected with genotype 1b; albeit without reaching statistical significance (0.49x10(6)+/-0.89x10(6) vs 1.44x10(6)+/-1.9x10(6) copies/microg of total RNA; p=NS). No relationships were observed between liver viral burden and age, risk factor status, duration of infection, ferritin and alanine aminotransferase levels or with grading and staging. CONCLUSIONS: Hepatitis C virus load in serum is a mirror of intrahepatic hepatitis C virus levels. Chronic alcohol consumption enhances intrahepatic hepatitis C virus concentration. PMID- 11785718 TI - Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report. AB - We report the first case of acute cholestatic hepatitis induced by bupropion. This antidepressant was taken by a 49-year-old female as adjuvant treatment to stop smoking. After 20 days of bupropion, the patient presented a symptomatology characterized by asthenia, nausea and scleral icterus and biochemical analyses showed a dramatic increase in direct bilirubin (up to 28 mg/dl) and transaminases (up to 68-fold normal limits). Antinuclear antibodies were positive (title = 1:80; speckled pattern). Biochemical analyses and antinuclear antibodies were normal two years earlier. The histology showed a pattern of acute hepatitis with involvement of bile ducts and with features of centrolobular cholestasis. Treatment with methylprednisolone was commenced and continued for 20 days. Liver enzymes and bilirubin returned to normal within two months of withdrawal of bupropion and remained normal during the 4-month follow-up. Antinuclear antibodies also became negative. Other causes of liver damage were excluded. Considering the clinical diagnostic scale for hepatotoxic adverse drug reaction, our patient showed a score compatible with the final diagnosis of bupropion related cholestatic hepatitis. PMID- 11785719 TI - Changes in gastric mucosa and luminal environment during acid-suppressive therapy: a review in depth. AB - Acid-suppressive therapy and subsequent changes in gastric mucosa and luminal environment rank highly amongst the investigated issues in gastroenterology over the past two to three decades. Herewith, we present an overview of these intragastric changes, particularly during long-term administration of acid suppresive medication and concurrent infection with Helicobacter pylori. Current evidence indicates that: i) Long-term acid suppression facilitates the development of fundic ECL cell hyperplasia, especially in the presence of Helicobacter pylori. No neoplastic changes directly attributable to acid suppression have so far been demonstrated in humans. ii) Acid-suppressive therapy increases the risk of enteric infections. iii) Acid-suppressive therapy does not alter fat and mineral bioavailability, but may decrease the absorption of protein bound vitamin B12. iv) Acid suppression invariably results in intragastric overgrowth of non-Helicobacter pylori bacterial species. The concurrent infection with Helicobacter pylori may promote this bacterial overgrowth and the intragastric formation of N-nitrosamines. v) Acid-suppressive therapy alters the natural course of Helicobacter pylori gastritis, transforming the antral predominant pattern into a body-predominant pattern, which in turn may progress to body gland atrophy. The pathophysiology of this phenomenon is currently under investigation. vi) In view of the potential adverse effects of acid suppression in the presence of Helicobacter pylori, the screen-and-treat strategy is advocated for Helicobacter pylori in subjects considered for long-term treatment. PMID- 11785720 TI - Improving opportunities for effective management of gastro-oesophageal reflux disease. AB - The recent introduction of proton pump inhibitors has extraordinarily improved the therapeutic approach to gastro-oesophageal reflux disease. The concept of decreasing gastric acid secretion and increasing the pH in the lower oesophagus has been demonstrated to be therapeutically effective and the higher the level of pH achieved, the better the results. In spite of the evident efficacy of these molecules, there are still many patients who will continue to have symptoms despite medical treatment. Proton pump inhibitors suppress gastric acidity, but this effect shows a remarkable interindividual variation depending on different reasons. Thus, it is still possible to optimise medical therapy for gastro oesophageal reflux disease. Esomeprazole, the S-isomer of omeprazole, has an advantageous metabolism and this particular feature translates into superior clinical efficacy. Clinical trials for initial and long-term treatment across the gastro-oesophageal reflux disease spectrum, have clearly demonstrated the superiority of esomeprazole over omeprazole, even if tolerability and safety are very similar. PMID- 11785721 TI - Treatment of erosive oesophagitis with omeprazole: a comparison with different delivery system. PMID- 11785722 TI - Multi-resistant idiopathic thrombocytopenia successfully treated by eradication of Helicobacter pylori. PMID- 11785723 TI - In chronic gastritis with atrophy, biopsy sampling underestimates Helicobacter pylori infection. PMID- 11785724 TI - The clinical examination for neuromuscular disease. AB - Neuromuscular disease can present even the most astute clinician with a challenging diagnostic dilemma. This article focuses on the neuroanatomy and the historical, physical, and neurologic examination findings observed in many of the neuromuscular disorders affecting dogs and cats. In addition, some common laboratory tests and imaging modalities used in the diagnosis of neuromuscular disease, including routine radiography, computed tomography, and magnetic resonance imaging, are discussed. A brief discussion of sensory nerve disorders is also presented. PMID- 11785725 TI - Muscular dystrophies and other inherited myopathies. AB - It is certain that more inherited neuromuscular disorders of dogs and cats will be identified as the ability of practicing veterinarians to recognize disorders of muscle, nerve, and neuromuscular junction improves and newer diagnostic tests become available. Two specific points are critical. Before DNA-based genetic tests and specific therapies can be developed, an accurate description of the problem, clinically and histopathologically, must be performed. This is particularly important for the accuracy of a pedigree analysis, because inclusion of dogs with unrelated problems would alter the interpretation. Second, animals with inherited breed-associated disease should not be bred for generation of companion animals. PMID- 11785726 TI - Neuromuscular complications in endocrine and metabolic disorders. AB - Many of the endocrine and metabolic myopathies have no unique features, and for most clinicians, it is not possible to remember the clinical nuances of all the specific abnormalities and deficiencies responsible for these myopathies. This can make this group of diseases difficult to suspect. It is more important to recognize the general features of myopathic disease and to consider muscle biopsies as a preliminary diagnostic technique, with the potential for further investigation if a myopathy is confirmed. PMID- 11785727 TI - Inflammatory myopathies. AB - Inflammatory myopathies are the result of infiltration of inflammatory cells into striated muscle, with or without an association with an underlying cause. Two broad classifications are IIMs and secondary inflammatory myopathies associated with other diseases. Standard diagnostic criteria for inflammatory myopathy include the presence of weakness or loss of specific muscle group function, an increase in CK, EMG changes associated with muscle membrane instability, and histologic evidence of inflammation. Not all these criteria, however, must be present. Fresh-frozen biopsy from two proximal muscles is recommended for biopsy confirmation. IIM can either focally affect head or neck muscles or be more diffuse. MMM is an immune-mediated disease characterized by a humoral antibody produced against the unique type IIM and type I variant mvofibers of masticatory muscles of dogs, which causes inflammation and loss of function of the muscles of mastication. Idiopathic polymyositis can affect focal muscle groups (extraocular, laryngeal) or present as multifocal or diffuse involvement of skeletal muscle in the cat and dog. Familial canine DM is an inflammatory disease of the striated muscle, skin, and vasculature in young Collies, Shetland Sheepdogs (Shelties), and, rarely, Collie-crossbred dogs. Immunosuppressive therapy is the key to successful treatment. Protozoal parasitic myopathies are the most common cause of clinically relevant secondary inflammatory myopathies. The degree of systemic involvement is often the limiting factor to successful treatment. Early recognition of the clinical signs for proper diagnostic testing and institution of appropriate therapy can result in a rewarding outcome in treating inflammatory myopathies in the cat and dog. PMID- 11785728 TI - Myotonia and disorders of altered muscle cell membrane excitability. AB - Altered excitability of the skeletal muscle membrane (sarcolemma) can result in clinical signs of muscle dysfunction. Hyperexcitability of the sarcolemma results in myotonia, and hypoexcitability results in paresis or paralysis. Our understanding of the physiologic and molecular bases of disorders of sarcolemmal excitability is rapidly increasing as techniques for evaluation are improved. This article reviews muscle excitability disorders in dogs and cats and their pathogenesis. PMID- 11785729 TI - Myasthenia gravis and disorders of neuromuscular transmission. AB - Myasthenia gravis is a disorder of neuromuscular transmission that occurs in congenital and acquired autoimmune forms. Acquired myasthenia gravis is probably the most common neuromuscular disorder in dogs that can be diagnosed and treated. An early, accurate diagnosis and appropriate therapy is of utmost importance to a good clinical outcome in this disorder. This article focuses on the diagnosis and treatment of acquired myasthenia gravis in dogs and cats with brief discussions of other disorders of neuromuscular transmission, including congenital myasthenia gravis, tick paralysis, botulism, and organophosphate intoxication. PMID- 11785730 TI - Acquired canine peripheral neuropathies. AB - Accurate diagnosis of the many causes of acute and chronic peripheral neuropathy in the dog presents a challenging prospect for any clinician. Being able to accurately localize the observed neurologic signs to the peripheral nervous system is the first challenge. Once this is accomplished, a logical series of diagnostic steps should be pursued so as to have the best chance of reaching a final etiologic diagnosis. Specific therapy can then be instituted to attempt to halt or, in some cases, reverse the peripheral nerve dysfunction. PMID- 11785731 TI - Dysautonomia and autonomic neuropathies. AB - The autonomic nervous system can be affected as part of a more diffuse peripheral nerve disease such as inflammatory polyneuropathy or diabetes, or as a primary disease, such as dysautonomia. Dysautonomia is being diagnosed with increasing frequency in dogs and other species in the Midwest. Affected animals present with absence of parasympathetic and autonomic ganglia and brainstem nuclei degenerate with minimal inflammation. The cause is unknown and treatment symptomatic. PMID- 11785732 TI - Muscle disorders and rehabilitation in canine athletes. AB - Muscle disorders associated with physical exertion in human athletes include delayed-onset muscle soreness, muscle strain, muscle tears, rhabdomyolysis, and acute and chronic compartment syndromes. Given that the structure of muscle is similar among different species, it is reasonable to expect that dogs experience the same phenomena. This article focuses on several of the muscle disorders of bird dogs, namely, coccygeal muscle injury and infraspinatus muscle contracture, and on those of dogs involved in tracking-obedience-protection training, namely, fibrotic myopathy, with an additional discussion of muscle strain. For injury prevention, one important area that can be adapted to canine athletes is the incorporation of warm-up and cool-down into the training program. PMID- 11785733 TI - Molecular diagnosis of inherited neuromuscular disease. AB - Prevention of inherited disease in companion animals is largely dependent on prebreeding identification of carriers of autosomal recessive disease traits. Molecular diagnosis is emerging as a convenient and reliable method of carrier detection, but few molecular diagnostic tests of inherited neuromuscular disease are readily available. New test development depends on investigations to determine disease genes and the disease causing mutations. A general approach to molecular diagnosis of inherited disorders is discussed. PMID- 11785734 TI - Electrophysiology in neuromuscular disease. AB - Electrophysiologic assessment of the peripheral nervous system is an integral part of the diagnostic workup for neuromuscular disease. This article is designed to provide insight into the importance and limitations of the various testing procedures now available in veterinary electrophysiology and to provide the reader with an understanding of the theory behind each of these procedures. The article also provides a guideline for the interpretation and clinical significance of each of the available tests. PMID- 11785735 TI - Muscle and nerve biopsy. AB - Biopsy of muscle and nerve is an essential component of the diagnostic plan for animals with suspected neuromuscular disease. This article includes descriptions of the biopsy procedures and information regarding appropriate biopsy site selection and correct handling and processing of the tissues. The normal and pathological appearance of muscle and nerve using routine histochemical and histological techniques are described and illustrated emphasizing the basic myopathic and neuropathic responses of the neuromuscular system. PMID- 11785736 TI - What is evidence based dentistry? AB - The insurmountable mass of literature and lectures that the modern practitioner is exposed to has created problems. The resolution of often contradictory information is not easy to discern. Evidence based dentistry presents guidelines to determine the validity of the results and whether they can be applied to clinical practice. This article introduces the reader to the basic principles to be used in and evidence based practice. PMID- 11785737 TI - The question. AB - This exercise of isolating the strongest article from the found titles should take no more than 1 to 2 minutes. Thus, the whole process of searching for the best evidence should take no more than 5 minutes. In medical practices where evidence based practice is done routinely, this process can be completed in less than 1 minute. Obviously, the evaluation could not have been made as expeditiously without the benefit of the specific details articulated in the question. The question focused the search terms and expedited the identification of the strongest evidence that directly addressed the patient's problem from among the found titles. It provided the dentist with good (but not compelling) evidence to support an answer to the patient. It also provided the dentist with a new piece of information to use the next time the problem of reduced implant support comes up. The dentist has thus enjoyed the satisfaction of quickly identifying new knowledge and the confidence that comes with its use. In addition, the information has provided the dentist with a small but important block against the deterioration of clinical judgment skills. PMID- 11785738 TI - Assessment of key elements to determine causation and risk factors in dentistry. AB - The best research method for assessing therapeutic modalities is the RCT. The prospective nature and the randomization of the subjects in an RCT provide the greatest opportunity to control bias and offer the most valid answer to the clinical question. Observational studies generate hypotheses about causation and should be viewed as a first step in the continuum of health care delivery. The preponderance of evidence will mount as the hypotheses are tested by additional prospective, longitudinal, observational trials. The clinician's involvement is to design and implement therapeutic strategies to alter the causal exposure, intervene in the dose-response gradient, and block the pathophysiologic mechanisms. Dentistry is an art and a science. Moving through the continuum from causation hypothesis to therapeutic intervention is the science of dentistry. It is the science of dentistry that will change the scope of the profession in this millennium. PMID- 11785739 TI - Users' guide to the dental literature: how to use an article about prognosis. AB - With the growing need for documented efficacy of treatment and efficiency of rendering care, prosthodontists will serve their patients best when they fully understand the intricacies of clinical research and the results reported. This article proposes a structure for evaluating the literature that pertains to prognosis--the prediction of outcomes and frequency of such occurrences. PMID- 11785740 TI - Biostatistical consultation for dental research. AB - Dental science researchers do not really need a detailed, ready-at-hand knowledge of statistics to design and perform high quality scientific research. Although the acquisition and utilization of such knowledge by dental researchers is not discouraged, it is proposed that it is more important for dental researchers to be committed to developing and maintaining a long term, ongoing, interactive consulting relationship with a biostatistician. The nature of this relationship will depend in large part on the complexity of the dental research being conducted. While the statistical consultant will assist in interpreting analytic results for the dental researcher, the latter will need to provide extensive input in assisting in the estimation of sample size and power, and for expressing scientific hypotheses in statistical terms so that the appropriate data analytic methodology can be specified. PMID- 11785741 TI - Applying evidence based dentistry to your patients. AB - It should be evident by now that evidence based dentistry leaves much room for the application of clinical judgment to the literature. This article points out that judgment in evaluating certain factors is essential and that the practice of evidence based dentistry is not a process of blindly following the conclusions found in the literature. Clinicians can safeguard the patient and themselves against the inappropriate use of weak or irrelevant evidence in the conduct of daily practice. This skill adds confidence to decision making in clinical practice and prevents the decline in skills throughout a career. PMID- 11785742 TI - Therapy: anecdote, experience, or evidence? AB - In dentistry, most changes in therapy come from new techniques and products that are introduced to the market. Clinicians (and patients) can be overwhelmed by advertisements and marketing, some obvious and some (e.g., paid clinical reports in non-peer-reviewed journals) not so obvious. Because most advances are made with small case studies, which are at a lower level of evidence, it is imperative that data clinicians read or see have the greatest validity possible. This validity is imperative to achieve evidence-based dentistry that uses relevant, high-quality, clinically oriented research that provides better information for the clinician and better treatment for the patient. PMID- 11785743 TI - The ethics of experimenting in dental practice. AB - Experiments, in the sense of novel actions taken with only a probable chance of success, are common in dental practice. Use of new materials or techniques learned in continuing education courses are examples. The grounds for ethically defensible experiments include (a) undertaken for the patient's sake, (b) within the standard of care, (c) having a reason for expected success, and (d) performed reflectively. A taxonomy of experiments is presented. The ethical context for this paper is discursive ethics, an approach that emphasizes the right of all affected to participate in mutual acceptance of the action. PMID- 11785744 TI - Conducting a search of the literature. AB - The purpose of this article is to show how to search the literature for articles that may be appropriate in answering a particular question related to patient care. PMID- 11785745 TI - Evidence based dentistry: design architecture. AB - It is important for clinicians to understand the type of clinical studies that appear in the literature and the inherent strengths and limitations of each study. The three possible alternative explanations, chance, bias, and confounding, must be considered for any research study. Thus, it is important to evaluate research studies critically in light of this discussion and not simply to summarize the findings. Finally, conclusions about causality can only be made on the body of evidence, not on any single study. PMID- 11785746 TI - Bias in dental research can lead to inappropriate treatment selection. AB - The first RCT was instituted in the early 1950s, evaluating streptomycin and bed rest compared with bed rest alone for tuberculosis. This research design has become the reference standard for comparative evaluations of therapies because of its prospective nature and the ability to control bias. Because it is easier to conduct observational studies, they have often been inappropriately substituted for the better experimental study designs. Since the 1950s, however, readers of the medical literature have slowly come to demand quality clinical research to assist them in caring for their patients. Dentists are somewhat behind their medical colleagues in using the strongest research designs to answer clinical questions. In dentistry, observational studies with convenience samples of patients have been commonly used. It is often argued that few dental ailments affect a person's life as negatively as most medical maladies; therefore, experimental rigors are not required of dental research. Although most dental care does not involve life-and-death issues, dentists are as eager as physicians to offer their patients optimal care. Optimal care is best defined through nonbiased research strategies. PMID- 11785747 TI - Systematic reviews of the literature: the overview and meta-analysis. AB - Systematic reviews in the form of overviews or meta-analyses offer a solution for busy practitioners who have difficulty keeping abreast of current literature. Because systematic reviews can condense numerous studies into reliable and valid summaries of the best available evidence for a specific clinical problem, they offer significant benefit to busy clinicians. This article has summarized the major features and advantages of systematic reviews. It has distinguished those features that attempt to increase the usefulness of reviews by limiting bias, and it provided a summary of important questions clinicians can use to appraise such reviews critically. With this knowledge, clinicians should be able to use the literature more appropriately and in a timely fashion. PMID- 11785748 TI - The use of diagnostic data in clinical dental practice. AB - This article has briefly introduced the dental clinician to the principles and practical application of diagnostic decision analysis. There are trade-offs and uncertainties in the process of arriving at a diagnosis, but they can be understood and controlled. First, the clinician must understand the significance of disease prevalence and assign to the patient an initial probability of disease being present. The clinician must then determine if further diagnostic measurements or tests are warranted. If so, the appropriate test must be selected, based on the ability of the test to revise the initial pretest probability. When a diagnostic test is positive, the clinician must know the probability that disease is actually present. The clinician must also know the probability that disease is actually present if the test result is negative. The astute clinician will calculate the posttest probabilities before proceeding with a test and will base treatment decisions on test results in accordance with predetermined test and test-treatment thresholds. PMID- 11785749 TI - Action research: a systematic review and guidance for assessment. PMID- 11785750 TI - Two-dimensional infrared spectroscopy: a promising new method for the time resolution of structures. AB - Recently, new methods for determining time-evolving structures using infrared analogs of NMR spectroscopy have been introduced that have outstanding potential in structural biology. Already, within the past two years, structures of dipeptides, tripeptides and pentapeptides have been determined on much faster timescales than the conformational dynamics. Also, two-dimensional infrared correlation spectra of some proteins and isotopically edited alanine-rich helices have been examined. PMID- 11785751 TI - Pulsed electron paramagnetic resonance methods for macromolecular structure determination. AB - Pulsed electron paramagnetic resonance (EPR) distance measurement techniques target macromolecular structure elucidation at both the local and global level. Recent developments in pulse microwave technology and high-field EPR have led to the development of a variety of pulsed EPR distance measurement techniques. These methods have emerged as powerful tools for the determination of structure/function relationships in macromolecular systems. In this review article, we discuss recent applications of long-range and short-range EPR distance measurements. PMID- 11785752 TI - Dipolar couplings as a probe of molecular dynamics and structure in solution. AB - The introduction of residual dipolar coupling methodology has increased the scope of structural biological problems that can be addressed by NMR spectroscopy. Conformational changes, the relative orientation of domains, and intermolecular complexes can now be characterized accurately and rapidly using NMR. The development of residual dipolar coupling methodology for the rapid recognition of homologous protein folds and for studies of submillisecond timescale dynamics has also seen considerable progress. PMID- 11785753 TI - Biophysical approaches to membrane protein structure determination. AB - Recently, there have been several technical advances in the use of solution and solid-state NMR spectroscopy to determine the structures of membrane proteins. The structures of several isolated transmembrane (TM) helices and pairs of TM helices have been solved by solution NMR methods. Similarly, the complete folds of two TM beta-barrel proteins with molecular weights of 16 and 19 kDa have been determined by solution NMR in detergent micelles. Solution NMR has also provided a first glimpse at the dynamics of an integral membrane protein. Structures of individual TM helices have also been determined by solid-state NMR. A combination of NMR with site-directed spin-label electron paramagnetic resonance or Fourier transform IR spectroscopy allows one to assemble quite detailed protein structures in the membrane. PMID- 11785754 TI - Electron cryomicroscopy methods. AB - Electron cryomicroscopy methods comprise a rapidly expanding field providing insights into the structure and function of biological macromolecules and their supramolecular assemblies. The 3.8 A resolution structure of the membrane protein aquaporin, a view of the herpesvirus capsid at 8.5 A and the 10 A resolution structure of the spliceosomal U1 small nuclear ribonucleoprotein complex are three outstanding examples emphasizing the versatility of this technique. PMID- 11785755 TI - Thermodynamic insights into proteins from NMR spin relaxation studies. AB - NMR spin relaxation measurements of picosecond to nanosecond timescale backbone and sidechain fluctuations of protein molecules, and subsequent entropic interpretation yield interesting, but sometimes counterintuitive, insights into proteins. The stabilities of proteins and protein interactions are achieved through enthalpy-entropy compensation, which is partitioned between the backbone and sidechains depending on the nature of the system. PMID- 11785756 TI - Direct measurement of protein binding energetics by isothermal titration calorimetry. AB - Of all the techniques that are currently available to measure binding, isothermal titration calorimetry is the only one capable of measuring not only the magnitude of the binding affinity but also the magnitude of the two thermodynamic terms that define the binding affinity: the enthalpy (AH) and entropy (AS) changes. Recent advances in instrumentation have facilitated the development of experimental designs that permit the direct measurement of arbitrarily high binding affinities, the coupling of binding to protonation/deprotonation processes and the analysis of binding thermodynamics in terms of structural parameters. Because isothermal titration calorimetry has the capability to measure different energetic contributions to the binding affinity, it provides a unique bridge between computational and experimental analysis. As such, it is increasingly becoming an essential tool in molecular design. PMID- 11785757 TI - Atomic force microscopy of macromolecular interactions. AB - The introduction of functional imaging tools and techniques that operate at molecular-length scales has provided investigators with unique approaches to characterizing biomolecular structure and function relationships. Recent advances in the field of scanning probe techniques and, in particular, atomic force microscopy have yielded tantalizing insights into the dynamics of protein self assembly and the mechanics of protein unfolding. PMID- 11785758 TI - The use of FRET imaging microscopy to detect protein-protein interactions and protein conformational changes in vivo. AB - Intermolecular and intramolecular FRET between two spectrally overlapping green fluorescent protein variants fused to two different host proteins or at two different sites within the same protein offers a unique opportunity to monitor real-time protein-protein interactions or protein conformational changes. By using fluorescence digital imaging microscopy, one can visualize the location of green fluorescent proteins within a living cell and follow the time course of the changes in FRET corresponding to cellular events at a millisecond time resolution. The observation of such dynamic molecular events in vivo provides vital insight into the action of biological molecules. PMID- 11785759 TI - Biophysical studies by ultracentrifugation. AB - Advances in data analysis are broadening the applicability of ultracentrifugation to the characterization of macromolecular behavior in complex solution. The direct fitting of sedimentation velocity data to the Lamm equation is emerging as a very powerful means to characterize size distributions, improve the precision of data analysis and increase experimental throughput. With improvements in data acquisition and analysis, ultracentrifugation is poised to make significant contributions to our understanding of how macromolecules behave in vivo. PMID- 11785760 TI - New approaches to the chemical synthesis of bioactive oligosaccharides. AB - The past year has seen some major advances in the area of carbohydrate synthesis using chemical methods. Progress in all areas of synthetic methodology, including new protecting groups and coupling methods, has been reported. A number of complex carbohydrate structures have been prepared using known, as well as new, methods. The goal to allow nonspecialists access to defined carbohydrate structures for biochemical, biophysical and biological studies has drawn closer by the introduction of two approaches towards synthesis automation. A one-pot glycosylation strategy utilized computer-assisted synthesis planning and the first solid-phase automated synthesizer was introduced very recently. PMID- 11785761 TI - Glycoside hydrolases and glycosyltransferases: families and functional modules. AB - The past year has witnessed the expected increase in the number of solved structures of glycoside hydrolases and glycosyltransferases, and their constitutive modules. These structures show that, while glycoside hydrolases display an extraordinary variety of folds, glycosyltransferases and carbohydrate binding modules appear to belong to a much smaller number of folding families. PMID- 11785762 TI - Genetic defects in N-glycosylation and cellular diversity in mammals. AB - Glycoproteins in mammalian cells are modified with complex-type aspargine-linked glycans of variable chain lengths and composition. Observations of mice carrying mutations in glycosyltransferase genes imply that N-glycan structures regulate T cell receptor clustering and hence sensitivity to agonists. We argue that the heterogeneity inherent in N-glycosylation contributes to cellular diversity and, thereby, to adaptability in the immune system. PMID- 11785763 TI - Proteins involved in the production and perception of oligosaccharides in relation to plant and animal development. AB - Chitin oligosaccharides and their derivatives are involved in developmental and defence-related signalling pathways. Major advances include the structural identification of lectins involved in development that bind chitin oligosaccharides and the links between chitin oligosaccharide and hyaluronan synthesis. Also, recent advances in the understanding of the biological role of oligosaccharides are summarised in a model for multistep glycan recognition. PMID- 11785764 TI - Hyaluronan: polysaccharide chaos to protein organisation. AB - Molecular dynamics simulations of hyaluronan have revealed the inherent flexibility of this glycosaminoglycan in solution. Crystal structures of hyaluronan-digesting enzymes have provided the first direct insights into the molecular basis of hyaluronan-protein interactions. Various studies on hyaluronan binding proteins suggest there is considerable diversity in their mode of interaction with hyaluronan, which might result in many different bound conformations of the polysaccharide. PMID- 11785765 TI - Order out of complexity--protein structures that interact with heparin. AB - Many proteins of widely differing functionality and structure are capable of binding heparin. Structural characterisations of the many types of such complexes are being reported in ever-increasing number and at improved resolution. Several crystal structures of complexes formed through the interaction of heparin-derived oligosaccharides with one or more protein partners have been described. PMID- 11785766 TI - Role of heparan sulfate in fibroblast growth factor signalling: a structural view. AB - Fibroblast growth factors (FGFs) are among the best-studied heparin-binding proteins, and heparan sulfate proteoglycans regulate FGF signalling by direct molecular association with FGF and its tyrosine kinase receptor, FGFR. Two recently determined crystal structures of FGF-FGFR-heparin complexes have provided new structural information on how heparin binds to FGF and FGFR, and lead to different models for receptor dimerisation. PMID- 11785767 TI - New structural insights into lectin-type proteins of the immune system. AB - New structural data have emerged for the ligand-binding sites of C-type lectin domains and C-type lectin-like domains of receptors of the immune system. These include binding sites for oligosaccharide or polypeptide ligands, or both oligosaccharide and polypeptide ligands. The structural basis for the binding of a lectin domain of the beta-trefoil family to different sulfooligosaccharide sequences has been revealed. Lectin activity has been documented for a beta/alpha TIM barrel fold that does not have the chitinase activity of the prototype enzyme with this fold. PMID- 11785768 TI - Gene expression of NMDA receptor subunits in rat adrenals under basal and stress conditions. AB - In addition to the central nervous system, glutamate receptors have been recently identified in a number of peripheral tissues, including adrenals. Pharmacological evidence indicates that adrenal glutamate receptors may be involved in stress response, particularly in catecholamine release. However, possible stress-induced changes at the level of local receptors themselves have not been evaluated yet. This study was aimed to investigate gene expression of N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A, NR2B) in rat adrenal gland under basal and stress conditions, using RT-PCR. NR1 mRNA was found to be present in the adrenal gland, while mRNAs coding for NR2-type subunits failed to be detected in adrenal tissue. The distribution of NR1 mRNA in rat adrenals showed higher concentrations in the adrenal medulla (228%) compared to those in the cortex. Single stress stimulus (immobilization) induced a significant increase of NR1 gene expression in both medullar (by 25%) and cortical (by 66%) regions of the adrenal gland at 24 h, while no changes were observed at 3 h after the stress exposure. It is possible that delayed rise in adrenal NR1 gene expression following stress exposure represents one of the factors by which stress exerts long-term effects on adrenal function at the molecular level. PMID- 11785769 TI - Spleen damage in endotoxaemic mice: the involvement of nitric oxide. AB - The association between Escherichia coli endotoxin-induced organ damage and nitric oxide-related mechanisms was investigated in the spleen of male Swiss albino mice (20-40 g) by using (1) Pt/Ir electrochemical sensor connected to an amperometric detection system (NO-501, InterMedical Co., Japan), (2) nitrotyrosine immunohistochemistry, (3) conventional light microscopy and (4) immunoblotting techniques in parallel. 1 h before endotoxin injection, animals were pretreated with either nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME, 20 mg kg(-1), i.p.) or inducible nitric oxide synthase expression inhibitor, dexamethasone (5 mg kg(-1), i.p.) or the inhibitor of murine inducible nitric oxide synthase in vivo, 2-amino-5,6-dihydro-6-methyl-4H 1,3-thiazine (AMT, 1 mg kg(-1), i.p.). 5 h after endotoxin treatment, electrochemically detected concentration of nitric oxide was significantly elevated (nM, endotoxin: 716.6 +/- 178.2, n = 10 vs saline: 209.4 +/- 127.8, n = 9, P = 0.0312, unpaired Student's t-test) and remained so throughout the 30 min monitorization period. Neither dexamethasone nor AMT blocked the endotoxin induced overproduction of nitric oxide indicating that the enhanced inducible nitric oxide synthase activity cannot be the only explanation. When dexamethasone and L-NAME combination was used to block both the constitutive and the inducible isoforms, nitric oxide production was virtually abolished, indicating a significant contribution from the constitutive isoform of nitric oxide synthase. The results of nitrotyrosine immunohistochemistry and the conventional light microscopy were also in agreement with the amperometric method while immunoblotting revealed the expression of both the endothelial and the inducible isoforms of nitric oxide synthase were induced endotoxaemic animals. Thus, conclude that endotoxin-induced splenic damage in endotoxaemia can be explained by enhanced production of nitric oxide due to the induction of both endothelial and inducible nitric oxide synthases while causal relationship and the roles of other deleterious mediators such as oxygen-derived free radicals are yet to be established. PMID- 11785770 TI - Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats. AB - Effect of long-term intake of isoleucine-proline-proline (IPP) and valine-proline proline (VPP), or a sour milk product containing these peptides on development of hypertension was investigated in spontaneously hypertensive rats (SHR). Six-week old SHR were given: 1) water (control group), 2) IPP and VPP dissolved in water (peptide group) or 3) sour milk containing IPP and VPP (sour milk group) for 12 weeks. Systolic blood pressure (SBP) was measured by tail-cuff method. Development of hypertension was attenuated in the groups receiving tripeptides or sour milk as compared to the control group. At the end of treatment period, SBP was 176 +/- 1 mmHg in sour milk group, 181 +/- 2 mmHg in peptide group, and 193 +/- 1 mmHg in control group (P < 0.001). After treatment withdrawal, SBP rose gradually reaching the level of control group within four weeks' follow-up. In functional bioassay of ACE inhibitory activity, effect of the tripeptides on angiotensin I or angiotensin II-induced contraction in rat mesenteric arteries was evaluated. IPP inhibited the angiotensin I-induced contraction, whereas the angiotensin II-induced contraction remained unaltered. In conclusion, long-term intake of IPP and VPP, or a sour milk containing these tripeptides attenuated the development of hypertension in SHR. One possible mechanism underlying this effect is ACE inhibition. PMID- 11785771 TI - Kynurenine and its metabolites in the rat with experimental renal insufficiency. AB - In uremia a great number of the endogenous metabolites that are ordinarily excreted in urine accumulate in the blood. Among these are the products of KYN degradation. In the present study we evaluated the peripheral KYN metabolism in the various stages of the rat experimental chronic renal insufficiency. Our results showed significant disturbances in peripheral kynurenic pathway, which resulted in the significant decrease of TRP plasma level and augmentation of concentration of its metabolites. The high concentrations of 3-hydroxykynurenine, xanthurenic acid, kynurenic acid, anthranilic acid and quinolinic acid positively correlated with degree of the renal insufficiency. Talking into account the biological properties of KYN metabolites, their accumulation in the blood, may be at least partially, responsible for severity of uremia as well as for uremic symptoms such as neuropathy, increased susceptibility to infections, hypertension, lipid disturbances and anemia. PMID- 11785772 TI - Hippocampal vasopressin (AVP) dialysis and the conditioned eyelid reflex in rabbits. AB - The role of arginine vasopressin (AVP) dialyzed into the hippocampus or caudate nucleus as the reference structure in the acquisition and extinction of the conditioned eyelid reflex in rabbit was investigated. Phonopneumatic stimulator was used for the generation of conditioned and unconditioned stimuli, and for control of the recorder. Opto-electronic sensor transduced the behavioral responses. Microdialysis probes were chronically implanted into the brain structures. AVP was dialyzed into the brain structures during the extinction procedure. Restraining of the process of extinction was shown during AVP dialysis through the hippocampus and caudate nucleus but the effect in hippocampus was stronger and longer lasting than in caudate nucleus. The influence of AVP dialyzed through the hippocampus on the course of acquisition was biphasic. Some insignificant improvement of leaming was observed at the beginning of training and then compensatory, significant restraining of learning. After AVP dialysis through the caudate nucleus only the late, insignificant tendency to improve leaming was shown. The effects of AVP were dose-dependent in inversely proportional manner and long-term in nature, especially the effects in hippocampus. PMID- 11785773 TI - tGLP-1 and release of vasopressin and oxytocin from the isolated rat hypothalamo neurohypophysial system: effects of a tGLP-1 receptor agonist and antagonist. AB - To date, glucagon-like peptide-1 (7-36) amide (tGLP-1) has been found to enhance the vasopressin and oxytocin secretion in vivo but not in vitro (i.e., when the isolated neurointermediate lobe of the pituitary was used for experiments). The goal of this study was to investigate whether tGLP-1 can influence the function of the hypothalamo-neurohypophysial complex in vitro. Also, the effect of a tGLP 1 agonist, exendin-4, and antagonist, exendin-(9-39), on the release of vasopressin/oxytocin from the isolated rat hypothalamo-neurohypophysial complex was tested. tGLP-1 enhanced the basal but not the potassium-stimulated release of vasopressin and oxytocin from the hypothalamo-neurohypophysial complex. On the other hand, tGLP-1 failed to affect the release of both hormones from the isolated neurointermediate lobe. The tGLP-1 agonist increased the secretion of oxytocin and vasopressin from the hypothalamo-neurohypophysial system whilst the tGLP-1 antagonist completely abolished the stimulatory effect of tGLP-1 on the secretion of both hormones. It is concluded that tGLP-1 affects the function of vasopressin- and oxytocinergic neurones through specific hypothalamic receptors. PMID- 11785774 TI - Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. AB - The involvement of prostaglandins synthesized by constitutive (COX-1) and inducible cyclooxygenase (COX-2) in central stimulation of the hypothalamic pituitary-adrenal (HPA) axis by adrenergic receptor agonists was investigated in conscious rats. COX-1 and COX-2 inhibitor, piroxicam (0.02 and 0.2 microg) and compound NS-398 (0.01 and 0.1 microg), respectively, were given intracerebroventricularly (i.c.v.) 15 min prior to i.c.v. adrenergic receptor agonists: phenylephrine (30 microg) and clonidine (10 microg), an alpha1- and alpha2-adrenergic agonist, and isoprenaline (20 microg) a non-selective beta adrenergic agonist and clenbuterol (10 microg) a selective beta2-adrenergic agonist. Piroxicam and NS-398 considerably and dose-dependently reduced the phenylephrine-induced increase in ACTH and corticosterone secretion. Pretreatment with piroxicam and NS-398 markedly impaired the clonidine-evoked ACTH and corticosterone secretion. Piroxicam moderately diminished the isoprenaline elicited increase in ACTH and corticosterone, while NS-398 did not markedly alter ACTH secretion. The clenbuterol-induced ACTH and corticosterone responses were considerably impaired by pretreatment with piroxicam, and slightly less potently by NS-398. These results indicate that in central structures involved in regulation of the HPA axis both constitutive and inducible cyclooxygenase are present under normal conditions in rats. These isoenzymes are significantly involved in the stimulatory signaling transduced by postsynaptic alpha1 adrenergic receptors and, to a lesser extent, by alpha2-adrenergic receptors. Both isoenzymes affect moderately the stimulatory action of a non-selective beta adrenergic agonist on ACTH and corticosterone secretion. COX-1 participates considerably and COX-2 markedly in the potent stimulatory action of selective beta2-adrenergic receptors on HPA axis. PMID- 11785775 TI - Effect of social stress on COX-1 and COX-2-induced alterations in the adrenergic agonists-evoked hypothalamic-pituitary-adrenal responses. AB - The purpose of the present study was to investigate the contribution of prostaglandins (PGs) synthesized by constitutive (COX-1) and inducible (COX-2) cyclooxygenase to stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic receptor agonists in rats under social crowing stress 3 days, (21 per a cage for 6) animals. The effects of phenylephrine, clonidine and isoprenaline, an alpha1-, alpha2- and beta-adrenergic agonist, respectively, in the presence and absence of COX-1 inhibitor, piroxicam, and COX-2 inhibitor, compound NS-398, on ACTH and corticosterone secretion in stressed rats were compared with these effects in non-stressed animals. All drugs were given intracerebroventricularly (i.c.v.), COX inhibitors 15 min before adrenergic agonists. Piroxicam (0.02 microg) and NS-398 (0.1 microg) significantly reduced the phenylephrine (30 microg) -induced ACTH and corticosterone secretion in both stressed and non stressed rats. Piroxicam (0.02 microg) and NS-398 (0.01 microg) moderately decreased the clonidine (10 microg) -evoked hormone responses in control rats but did not alter these responses in stressed rats. Piroxicam (0.2 microg) and NS-398 (0.1 microg) moderately diminished the isoprenaline (20 microg) -evoked ACTH and corticosterone response in control rats, while in stressed rats these inhibitors did not significantly alter the isoprenaline-induced rise in ACTH and corticosterone secretion. These results indicate that in hypothalamic structures involved in the regulation of adrenergic agonists-induced HPA stimulation COX-2 is expressed under physiological synaptic activity. Social crowding stress does not alter the significant involvement of prostaglandins in the HPA response induced by stimulation of central alpha1-adrenergic receptors. Prostaglandins are of lesser importance in activation of the HPA axis by alpha2- and beta-adrenergic receptors under basal and social stress conditions. PMID- 11785776 TI - Changes in pancreatic lysosomal enzymes activity as the potential factors leading to diabetic enteropathy. AB - The aim of this study was to establish and quantify changes in the activities of total, free and bound fractions of pancreatic lipase, galactoso-6-sulphatase, beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase in the course of alloxan induced diabetes mellitus. Rabbits were divided into a control group and groups injected with alloxan on the 21st, 42nd, 90th and the 180th day, after which blood samples were taken and the rabbits sacrificed by decapitation. The pancreas was removed and the glucose level measured. Enzyme activities were assayed by spectrophotometric methods. The total activities of N-acetyl-beta-D glucosaminidase and beta-D-galactosidase were the lowest on day 42 of the test, and the total activity of lipase was the highest at this point of time, as compared to the other periods of the study. We conclude that in the course of alloxan-induce diabetes activities of pancreatic lipase and sulphatase were increasing following the levels of glucose, whilst activities of beta-D galactosidase and N-acetyl-beta-D-glucosaminidase were declining, being inversely correlated to the level of glucose and activities of the first two mentioned enzymes. Above alterations in activity of lysosomal pancreatic enzymes of alloxan induced diabetic rabbits may be responsible for some aspects of previously reported diabetic enteropathy and chronic complications, or may provide a mechanism for the pancreatic beta-cells to moderate their insulin content. PMID- 11785777 TI - Does chronic ethanol administration have influence on pancreatic regeneration in the course of caerulein induced acute pancreatitis in rats. AB - This study was undertaken in order to determine the influence of chronic ethanol administration on pancreatic regeneration during acute pancreatitis (AP). Rats were pair fed with isocaloric diet containing or not ethanol. After 8 weeks of such feeding AP was induced by s.c. injection of caerulein (Cae). 6 h, 24 h and 5 days after first Cae dose pancreatic weight, amylase, chymotrypsin, protein, RNA, DNA contents were determined and phosphatidic acid (PA) production in isolated pancreatic acini was measured. Proliferating cells were quantified by immunochemical staining of cells incorporating bromodeoxyuridine (BrdU). RESULTS: Pancreatic weight was significantly higher at 6 h after first Cae injection in both, ethanol fed (EF) and control groups (C), however at 24 h pancreatic weight did not differ from prior to AP induction in EF rats. Ethanol feeding (EF) did not influence significantly protein, chymotrypsin and amylase content in pancreatic tissue in groups with AP. In EF rats RNA content after 5 days of AP was higher than in control animals. Total DNA content in EF rats with AP was lower 6 h after AP induction, earlier than in control animals with AP. Immunochemistry showed higher labelling index for BrdU after 6 h, 24 h and 5 days of AP in EF rats. In contrast to this findings, in EF animals, AP induction was not able to stimulate further PA accumulation. CONCLUSION: We conclude that chronic ethanol feeding, while inhibiting PA accumulation in comparison to control group, does not impair pancreatic tissue regeneration during the early phase of Cae-induced AP. Stimulation of regenerative/reparative processes in EF rats during Cae-induced AP seems to be even more pronounced than in the control group. PMID- 11785778 TI - The myoelectric activity of ileum in fasted and fed young pigs. AB - To precise the character of myoelectric activity of distal small intestine, in 8 young pigs 1 bipolar electrode was attached at the serosal side of the jejunum and 7 electrodes were sutured at terminal ileum. After the recovery, the animals were fed twice daily during at least 2 weeks and were fasted 24 h before each experiment. Myoelectric activity was recorded with electroencephalograph throughout the experiment lasting 3-5 h. After control recording the standard food was given during the end of ileal phase 1 of migrating myoelectric complex (MMC) and registration of myoelectric activity was continued. Ileal propagated or non-propagated minute rhythm was observed in 64% of the experiments performed, during phase 2b of MMC. In most animals studied, the long isolated spike burst series lasting 1-6 min and short isolated spike burst series lasting 15-25 s were observed. Feeding induced myoelectric activity in the jejunum usually after 1-2 min and, in the ileum, during most episodes, after 2-9 min, for 4-10 min. During and after feeding, the short-lasting "transient fed pattern" was observed. Mean propagation velocity of phase 3 MMC was 4.4 +/- 0.8 and 8.1 +/- 0.6 cm/min (mean +/- S.E.M., p > 0.05) before and after feeding, respectively. Phase 3 MMC was preceded by 2-3 spike burst series lasting 40-70 s each before feeding and 1-3 min after feeding. Single propagated spike bursts arrived more frequently after feeding. Two types of minute rhythm, propagated and stationary, were observed. Giant spike bursts, propagated contractions and ultrarapid spike rushes were recorded occasionally. In conclusion, the myoelectric activity of terminal ileum in swine is eventful, exhibits wide range of irregularity and its response to feeding is relatively weak and delayed as compared to the upper small intestine. PMID- 11785779 TI - Investigating potential anxiolytic, antidepressant and memory enhancing activity of deprenyl. AB - L-deprenyl in the dose of 0.25 mg/kg (the dose with no effect on locomotor activity) was administered to Wistar rats in single and prolonged treatment (21 days). In the same manner carboxymethyl cellulose was given to the control group. In the forced swimming test the rats from the deprenyl group showed reduced immobility time only once, after 7 days of treatment, as compared with the control group. In the Crawley's test one parameter was increased after deprenyl- the white square entries (WSE), showing that the rats were emboldened to move more freely in the white, lighted area. In the maze test the most important observations were that deprenyl shortened the food finding time and significantly counteracted the elongation of this time after scopolamine. The authors discuss the possibility that deprenyl has a modulatory effect on learning and memory and this effect depends on the dose used. It seems also that the increase of monoamine and cholinergic transmission may be involved. The small antidepressant and anxiolytic effect may be due to the metabolites of deprenyl of the amphetamine group. PMID- 11785781 TI - Oxidized low density lipoprotein inhibits prostacyclin generation by rat aorta in vitro: a key role of lysolecithin. AB - The objective of this study was to examine the effect of oxLDL on prostacyclin (PGI2) generation by rat aortic segments and to see whether the lipid fraction of oxLDL or its components are responsible for that effect. We also tested if antioxidants have any protective role. LDL oxidized by copper was characterized by higher TBARS, conjugated diene, lysophosphatidylcholine (lyso PC), oxysterols and less polyunsaturated fatty acids (PUFA) than nLDL. Preincubation of aortas with oxLDL caused a significant inhibition of PGI2 generation compared to aortas preincubated with nLDL or buffer only. The percent inhibition was dependent on the concentration of oxLDL. Most of the inhibitory effect of oxLDL resided in its lipid moiety while the lipid fraction of nLDL, as well as native LDL had no effect. Preincubation of aortas with 10 microg/ml of 7-ketocholesterol the major oxysterol in oxLDL reduced the amount of PGI2 generated by aorta at all times tested; however that decrease did not reach a significant level. Aortas preincubated with 10 microg/ml of lyso PC showed a 21-36% inhibition of PGI2 generation which was comparable to the inhibition produced by preincubating the aortas with 50 microg protein/ml of oxLDL (containing about 7.5 microg lyso PC). This indicated that most of the inhibitory effect of oxLDL was due to its lyso PC. The small molecular weight fraction (< 10 kDa) with a high level of TBARS (TBARS solution) also significantly decreased the PGI2 generation by aorta. Addition of superoxide dismutase (SOD) + catalase or vitamin E simultaneously with oxLDL or TBARS solution in the preincubation medium did not reverse their inhibitory effects. This indicated that oxygen free radicals are not a contributing factor to the inhibitory effect of oxLDL but lyso PC and the lipid peroxides and probably other components already present within oxLDL are the important inhibitors. PMID- 11785780 TI - 15-deoxy-delta12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells. AB - Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-gamma ligands 15-deoxy-delta12,14PGJ2 (15d PGJ2), delta12PGJ2, ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ2 (10 microM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50) of approximately 7 microM 15d-PGJ2. Delta12-PGJ2 also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ2 and delta12PGJ2, which may be independent of PPAR-gamma activation, requires further elucidation. PMID- 11785782 TI - Evidence for the involvement of the NADPH oxidase enzyme complex in the optimal accumulation of Platelet-activating factor in the human cell line PLB-985. AB - Platelet-activating factor (PAF) is an early product of the inflammatory environment, influencing development and resolution of inflammation. Its production is greater in neutrophils and macrophages, which predominantly synthesize 1-alkyl sn-2 acetyl glycerophosphocholine (GPC) than in nongranulocytes (B cells and endothelial cells), which lack a respiratory burst and synthesize 1-acyl sn-2 acetyl GPC as their major PAF species. This study investigated whether the respiratory burst was responsible for the quantitative and qualitative differences in sn-2 acetyl GPC species generation by neutrophils and macrophages versus those cells lacking the NADPH oxidase complex. The myeloid cell line PLB-985 (capable of differentiation into neutrophils) was used to test this hypothesis, since these cells had previously been generated with a non functional respiratory burst (X-CGD PLB-985). Differentiated PLB-985 cells underwent a large respiratory burst in response to PMA (phorbol ester), and smaller respiratory bursts in response to A23187 (calcium ionophore), and the bacterial polypeptide fMLP (receptor mediated activation). Concurrently, treated cells were assessed for production of 1-hexadecyl and 1-palmitoyl sn-2 acetyl GPC species by gas chromatography/mass spectrometry. Neither cell type generated these lipid species in response to PMA, but both cell types generated equal levels of sn-2 acetyl GPC in response to A23187, with five times more 1-hexadecyl than 1-palmitoyl species. Upon fMLP activation, X-CGD PLB-985 cells produced significantly less 1-hexadecyl and 1-palmitoyl sn-2 acetyl GPC in comparison to the wild-type PLB-985 cells. These findings suggest phagocytic oxidant production by NADPH oxidase is not essential for sn-2 acetyl GPC generation, but appears important for optimal production of PAF in response to some stimuli. PMID- 11785783 TI - Anti-inflammatory activity of a novel selective cyclooxygenase-2 inhibitor, FR140423, on type II collagen-induced arthritis in Lewis rats. AB - The mechanism of action of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4 (methylsulfinyl)-phenyl]pyrazole), a novel and selective cyclooxygenase (COX)-2 inhibitor, in rat type II collagen-induced arthritis was investigated and compared with that of indomethacin. We tested the inhibitory effects of FR140423 on paw edema and the formation of arachidonic acid metabolites in inflamed paws immunized with type II collagen. Oral administration of FR 140423 showed a dose dependent anti-inflammatory effect and was two-fold more potent than indomethacin. The increase of prostaglandin (PG) E2 and thromboxane (TX) B2 but not leukotriene B4 in inflamed paws was associated with the development of paw edema. FR140423 and indomethacin dose-dependently suppressed the levels of PGE2 and TXB2 in arthritic rat paws. Unlike indomethacin, FR140423 did not induce gastric lesions in arthritic rats. These results suggest that FR140423 shows a potent anti-inflammatory effect mediated by inhibition of prostanoids produced by COX-2 in inflamed tissues immunized with type II collagen, with a greatly improved safety profile compared to indomethacin. PMID- 11785786 TI - Comparison of voice F0 responses to pitch-shift onset and offset conditions. PMID- 11785790 TI - Small-slope scattering from rough elastic ocean floors: general theory and computational algorithm. AB - In this article acoustic scattering by a random rough interface that separates a fluid incident medium from an underlying uniform scattering medium, either fluid or elastic solid, in cases for which the Bragg scale lies within the power-law tail of the roughness spectrum is dealt with. The physical foundation is an inherently reciprocity-preserving, local small-slope theory. A fully bistatic formulation is developed for the scattering strength, together with a robust numerical implementation that allows a wide range of spectral exponent values. The practical result for ocean acoustics is a significantly improved description of the interface component of sea floor scattering. Calculations are presented to demonstrate the advantage of this approach over perturbation theory, and to illustrate its dependence on frequency and environmental parameters as well as its operation in bistatic geometries. PMID- 11785792 TI - Interpretation of the spectra of energy scattered by dispersed anchovies. AB - The spectra of backscattered energy by dispersed anchovies, which were reported by Holliday (1972), reveal several peaks at frequencies that correspond to theoretically calculated resonance frequencies of year classes of anchovies. Theoretical calculations are based on concurrent measurements of distributions of swim bladder dimensions and a modified form of Minnaert's (1933) equation. Differences between calculated and measured values of the mean lengths of the second-, third-, and fourth-year classes are within experimental uncertainties (+/-8%). The calculated mean lengths of juvenile anchovies are in good agreement with historical measurements of the bounds on this parameter (Butler, 1989). Matching of theoretical calculations and measurements of backscattered energy level versus frequency yields estimates of the total Q of the spectral line, QT, and the relative number density per year class. The resultant estimate of QT of adult anchovies is approximately 4.4. This value of QT is consistent with laboratory measurements of the Q of individual anchovies. Q0 (approximately 7 at 15 m) and measurements of length distributions of year classes and depth distributions. Resultant estimates of relative number densities of year classes were consistent with historical measurements of the relative number densities of year classes of anchovies in the Southern California Bight. PMID- 11785805 TI - Active control of the volume acquisition noise in functional magnetic resonance imaging: method and psychoacoustical evaluation. AB - Functional magnetic resonance imaging (fMRI) provides a noninvasive tool for observing correlates of neural activity in the brain while a subject listens to sound. However, intense acoustic noise is generated in the process of capturing MR images. This noise stimulates the auditory nervous system, limiting the dynamic range available for displaying stimulus-driven activity. The noise is potentially damaging to hearing and is distracting for the subject. In an active noise control (ANC) system, a reference sample of a noise is processed to form a sound which adds destructively with the noise at the listener's ear. We describe an implementation of ANC in the electromagnetically hostile and physically compact MRI scanning environment. First, a prototype system was evaluated psychoacoustically in the laboratory, using the electrical drive to a noise generating loudspeaker as the reference. This system produced 10-20 dB of subjective noise-reduction between 250 Hz and 1 kHz, and smaller amounts at higher frequencies. The system was modified to operate in a real MR scanner where the reference was obtained by recording the acoustic scanner noise. Objective reduction by 30-40 dB of the most intense component in scanner noises was realized between 500 Hz and 3500 Hz, and subjective reduction of 12 dB and 5 dB in tests at frequencies of 600 Hz and at 1.9 kHz, respectively. Although the benefit of ANC is limited by transmission paths to the cochlea other than air conduction routes from the auditory meatus, ANC achieves worthwhile attenuation even in the frequency range of maximum bone conduction (1.5-2 kHz). ANC should, therefore, be generally useful during auditory fMRI. PMID- 11785811 TI - Origin of the bell-like dependence of the DPOAE amplitude on primary frequency ratio. AB - For low and medium sound pressure levels (SPLs), the amplitude of the distortion product otoacoustic emission (DPOAE) recorded from guinea pigs at the 2f1-f2 frequency is maximal when f2/f1 approximately 1.23 and decreases for lower and higher f2/f1 ratios. The high-ratio slope of the DPOAE dependence on the ratio of the primary frequencies might be anticipated since the f1 amplitude at the f2 place is expected to decrease for higher f2/f1 ratios. The low-ratio slope of the dependence at low and medium SPLs of the primaries is actually one slope of a notch. The DPOAE amplitude recovers from the notch when the f2/f1 ratio is further reduced. In two-dimensional space formed by the f2/f1 ratio, and the levels of the primaries, the notch is continuous and has a level-dependent phase transition. The notch is identical to that seen in DPOAE growth functions. Similar notches and phase transitions were observed for high-order and high frequency DPOAEs. Theoretical analysis reveals that a single saturating nonlinearity is capable of generating similar amplitude notch and phase transition when the f2/f1 ratio is decreased because of the increase in f1 amplitude at the DPOAE generation place (f2 place). The difference between the DPOAE recorded from guinea pigs and humans is discussed in terms of different position of the operating point of the DPOAE generating nonlinearity. PMID- 11785812 TI - A human nonlinear cochlear filterbank. AB - Some published cochlear filterbanks are nonlinear but are fitted to animal basilar membrane (BM) responses. Others, like the gammatone, are based on human psychophysical data, but are linear. In this article, a human nonlinear filterbank is constructed by adapting a computational model of animal BM physiology to simulate human BM nonlinearity as measured by psychophysical pulsation-threshold experiments. The approach is based on a dual-resonance nonlinear type of filter whose basic structure was modeled using animal observations. In modeling the pulsation threshold data, the main assumption is that pulsation threshold occurs when the signal and the masker produce comparable excitation, that is the same filter output, at the place of the BM best tuned to the signal frequency. The filter is fitted at a discrete number of best frequencies (BFs) for which psychophysical data are available for a single listener and for an average response of six listeners. The filterbank is then created by linear regression of the resulting parameters to intermediate BFs. The strengths and limitations of the resulting filterbank are discussed. Its suitability for simulating hearing-impaired cochlear responses is also discussed. PMID- 11785813 TI - Distortion product otoacoustic emission input/output functions in normal-hearing and hearing-impaired human ears. AB - DPOAE input/output (I/O) functions were measured at 7f2 frequencies (1 to 8 kHz; f2/f1 = 1.22) over a range of levels (-5 to 95 dB SPL) in normal-hearing and hearing-impaired human ears. L1-L2 was level dependent in order to produce the largest 2f1-f2 responses in normal ears. System distortion was determined by collecting DP data in six different acoustic cavities. These data were used to derive a multiple linear regression model to predict system distortion levels. The model was tested on cochlear-implant users and used to estimate system distortion in all other ears. At most but not all f2's, measurements in cochlear implant ears were consistent with model predictions. At all f2 frequencies, the ears with normal auditory thresholds produced I/O functions characterized by compressive nonlinear regions at moderate levels, with more rapid growth at low and high stimulus levels. As auditory threshold increased, DPOAE threshold increased, accompanied by DPOAE amplitude reductions, notably over the range of levels where normal ears showed compression. The slope of the I/O function was steeper in impaired ears. The data from normal-hearing ears resembled direct measurements of basilar membrane displacement in lower animals. Data from ears with hearing loss showed that the compressive region was affected by cochlear damage; however, responses at high levels of stimulation resembled those observed in normal ears. PMID- 11785814 TI - Effects of draining cochlear fluids on stapes displacement in human middle-ear models. AB - Displacement-frequency characteristics of the stapes footplate were measured in five human temporal bones before and after draining the vestibule. Measurements were made in the 0.125-8 kHz range at 80 dB input sound pressure level, using a laser Doppler vibrometer. A circuit model was also used to predict stapes displacement. The temporal bone studies show a slight decrease in stapes footplate displacement at low frequency, and little change above 1 kHz. The displacement change is not as great as that found by other investigators or predicted by the model. There is little difference in stapes motion in temporal bones when the inner ear is intact or drained. PMID- 11785815 TI - Multicomponent stimulus interactions observed in basilar-membrane vibration in the basal region of the chinchilla cochlea. AB - Multicomponent stimuli consisting of two to seven tones were used to study suppression of basilar-membrane vibration at the 3-4-mm region of the chinchilla cochlea with a characteristic frequency between 6.5 and 8.5 kHz. Three-component stimuli were amplitude-modulated sinusoids (AM) with modulation depth varied between 0.25 and 2 and modulation frequency varied between 100 and 2000 Hz. For five-component stimuli of equal amplitude, frequency separation between adjacent components was the same as that used for AM stimuli. An additional manipulation was to position either the first, third, or fifth component at the characteristic frequency (CF). This allowed the study of the basilar-membrane response to off-CF stimuli. CF suppression was as high as 35 dB for two-tone combinations, while for equal-amplitude stimulus components CF suppression never exceeded 20 dB. This latter case occurred for both two-tone stimuli where the suppressor was below CF and for multitone stimuli with the third component=CF. Suppression was least for the AM stimuli, including when the three AM components were equal. Maximum suppression was both level- and frequency dependent, and occurred for component frequency separations of 500 to 600 Hz. Suppression decreased for multicomponent stimuli with component frequency spacing greater than 600 Hz. Mutual suppression occurred whenever stimulus components were within the compressive region of the basilar membrane. PMID- 11785816 TI - DPOAE suppression tuning: cochlear immaturity in premature neonates or auditory aging in normal-hearing adults? AB - Previous work has shown that distortion product otoacoustic emission (DPOAE) suppression tuning curves (STCs) recorded from premature neonates are narrower than adult STCs at both low and high frequencies. This has been interpreted to indicate an immaturity in cochlear function prior to term birth. However, an alternative explanation for this finding is that adult DPOAE STCs are broadened and reflect cochlear hair cell loss in normal-hearing adults due to aging, and natural exposure to noise and ototoxins. This alternative hypothesis can be tested by studying suppression tuning in normal-hearing school-aged children. If normal-hearing children, who have not aged significantly or been exposed to noise/ototoxins, have DPOAE suppression tuning similar to adults, the auditory aging hypothesis can be ruled out. However, if children have tuning similar to premature neonates and dissimilar from adults, it implicates aging or other factors intrinsic to the adult cochlea. DPOAE STCs were recorded at 1500, 3000, and 6000 Hz using optimal parameters in normal-hearing children and adults. DPOAE STCs collected previously from premature neonates were used for age comparisons. In general, results indicate that tuning curves from children are comparable to adult STCs and significantly different from neonatal STCS at 1500 and 6000 Hz. Only the growth of suppression was not adultlike in children and only at 6000 Hz. These findings do not strongly support the auditory aging hypothesis as a primary explanation for previously observed neonatal-adult differences in DPOAE suppression tuning. It suggests that these age differences are most likely due to immaturities in the neonatal cochlea. However, nonadultlike suppression growth observed in children at 6000 Hz warrants further attention and may be indicative of subtle alternations in the adult cochlea at high frequencies. PMID- 11785817 TI - Energy-independent factors influencing noise-induced hearing loss in the chinchilla model. AB - The effects on hearing and the sensory cell population of four continuous, non Gaussian noise exposures each having an A-weighted L(eq)=100 dB SPL were compared to the effects of an energy-equivalent Gaussian noise. The non-Gaussian noise conditions were characterized by the statistical metric, kurtosis (beta), computed on the unfiltered, beta(t), and the filtered, beta(f), time-domain signals. The chinchilla (n=58) was used as the animal model. Hearing thresholds were estimated using auditory-evoked potentials (AEP) recorded from the inferior colliculus and sensory cell populations were obtained from surface preparation histology. Despite equivalent exposure energies, the four non-Gaussian conditions produced considerably greater hearing and sensory cell loss than did the Gaussian condition. The magnitude of this excess trauma produced by the non-Gaussian noise was dependent on the frequency content, but not on the average energy content of the impacts which gave the noise its non-Gaussian character. These results indicate that beta(t) is an appropriate index of the increased hazard of exposure to non-Gaussian noises and that beta(f) may be useful in the prediction of the place-specific additional outer hair cell loss produced by non-Gaussian exposures. The results also suggest that energy-based metrics, while necessary for the prediction of noise-induced hearing loss, are not sufficient. PMID- 11785818 TI - Towards a measure of auditory-filter phase response. AB - This study investigates how the phase curvature of the auditory filters varies with center frequency (CF) and level. Harmonic tone complex maskers were used, with component phases adjusted using a variant of an equation proposed by Schroeder [IEEE Trans. Inf. Theory 16, 85-89 (1970)]. In experiment 1, the phase curvature of the masker was varied systematically and sinusoidal signal thresholds were measured at frequencies from 125 to 8000 Hz. At all signal frequencies, threshold differences of 20 dB or more were observed between the most effective and least effective masker phase curvature. In experiment 2, the effect of overall masker level on masker phase effects was studied using signal frequencies of 250, 1000, and 4000 Hz. The results were used to estimate the phase curvature of the auditory filters. The estimated relative phase curvature decreases dramatically with decreasing CF below 1000 Hz. At frequencies above 1000 Hz, relative auditory-filter phase curvature increases only slowly with increasing CF, or may remain constant. The phase curvature of the auditory filters seems to be broadly independent of overall level. Most aspects of the data are in qualitative agreement with peripheral physiological findings from other mammals, which suggests that the phase responses observed here are of peripheral origin. However, in contrast to the data reported in a cat auditory nerve study [Carney et al., J. Acoust. Soc. Am. 105, 2384-2391 (1999)], no reversal in the sign of the phase curvature was observed at very low frequencies. Overall, the results provide a framework for mapping out the phase curvature of the auditory filters and provide constraints on future models of peripheral filtering in the human auditory system. PMID- 11785819 TI - Spatio-temporal analysis of irregular vocal fold oscillations: biphonation due to desynchronization of spatial modes. AB - This report is on direct observation and modal analysis of irregular spatio temporal vibration patterns of vocal fold pathologies in vivo. The observed oscillation patterns are described quantitatively with multiline kymograms, spectral analysis, and spatio-temporal plots. The complex spatio-temporal vibration patterns are decomposed by empirical orthogonal functions into independent vibratory modes. It is shown quantitatively that biphonation can be induced either by left-right asymmetry or by desynchronized anterior-posterior vibratory modes, and the term "AP (anterior-posterior) biphonation" is introduced. The presented phonation examples show that for normal phonation the first two modes sufficiently explain the glottal dynamics. The spatio-temporal oscillation pattern associated with biphonation due to left-right asymmetry can be explained by the first three modes. Higher-order modes are required to describe the pattern for biphonation induced by anterior-posterior vibrations. Spatial irregularity is quantified by an entropy measure, which is significantly higher for irregular phonation than for normal phonation. Two asymmetry measures are introduced: the left-right asymmetry and the anterior-posterior asymmetry, as the ratios of the fundamental frequencies of left and right vocal fold and of anterior-posterior modes, respectively. These quantities clearly differentiate between left-right biphonation and anterior-posterior biphonation. This paper proposes methods to analyze quantitatively irregular vocal fold contour patterns in vivo and complements previous findings of desynchronization of vibration modes in computer modes and in in vitro experiments. PMID- 11785820 TI - A method of applying Fourier analysis to high-speed laryngoscopy. AB - A new method for analysis of digital high-speed recordings of vocal-fold vibrations is presented. The method is based on the extraction of light-intensity time sequences from consecutive images, which in turn are Fourier transformed. The spectra thus acquired can be displayed in four different modes, each having its own benefits. When applied to the larynx, the method visualizes oscillations in the entire laryngeal area, not merely the glottal region. The method was applied to two laryngoscopic high-speed image sequences. Among these examples, covibrations in the ventricular folds and in the mucosa covering the arytenoid cartilages were found. In some cases the covibrations occurred at other frequencies than those of the glottis. PMID- 11785821 TI - Effects of ethanol intoxication on speech suprasegmentals. AB - The effects of ingesting ethanol have been shown to be somewhat variable in humans. To date, there appear to be but few universals. Yet, the question often arises: is it possible to determine if a person is intoxicated by observing them in some manner? A closely related question is: can speech be used for this purpose and, if so, can the degree of intoxication be determined? One of the many issues associated with these questions involves the relationships between a person's paralinguistic characteristics and the presence and level of inebriation. To this end, young, healthy speakers of both sexes were carefully selected and sorted into roughly equal groups of light, moderate, and heavy drinkers. They were asked to produce four types of utterances during a learning phase, when sober and at four strictly controlled levels of intoxication (three ascending and one descending). The primary motor speech measures employed were speaking fundamental frequency, speech intensity, speaking rate and nonfluencies. Several statistically significant changes were found for increasing intoxication; the primary ones included rises in F0, in task duration and for nonfluencies. Minor gender differences were found but they lacked statistical significance. So did the small differences among the drinking category subgroups and the subject groupings related to levels of perceived intoxication. Finally, although it may be concluded that certain changes in speech suprasegmentals will occur as a function of increasing intoxication, these patterns cannot be viewed as universal since a few subjects (about 20%) exhibited no (or negative) changes. PMID- 11785822 TI - Surrogate analysis for detecting nonlinear dynamics in normal vowels. AB - Normal vowels are known to have irregularities in the pitch-to-pitch variation which is quite important for speech signals to be perceived as natural human sound. Such pitch-to-pitch variation of vowels is studied in the light of nonlinear dynamics. For the analysis, five normal vowels recorded from three male and two female subjects are exploited, where the vowel signals are shown to have normal levels of the pitch-to-pitch variation. First, by the false nearest neighbor analysis, nonlinear dynamics of the vowels are shown to be well analyzed by using a relatively low-dimensional reconstructing dimension of 4 < or = d < or = 7. Then, we further studied nonlinear dynamics of the vowels by spike-and-wave surrogate analysis. The results imply that there exists nonlinear dynamical correlation between one pitch-waveform pattern to another in the vowel signals. On the basis of the analysis results, applicability of the nonlinear prediction technique to vowel synthesis is discussed. PMID- 11785823 TI - A two-microphone dual delay-line approach for extraction of a speech sound in the presence of multiple interferers. AB - This paper describes algorithms for signal extraction for use as a front-end of telecommunication devices, speech recognition systems, as well as hearing aids that operate in noisy environments. The development was based on some independent, hypothesized theories of the computational mechanics of biological systems in which directional hearing is enabled mainly by binaural processing of interaural directional cues. Our system uses two microphones as input devices and a signal processing method based on the two input channels. The signal processing procedure comprises two major stages: (i) source localization, and (ii) cancellation of noise sources based on knowledge of the locations of all sound sources. The source localization, detailed in our previous paper [Liu et al., J. Acoust. Soc. Am. 108, 1888 (2000)], was based on a well-recognized biological architecture comprising a dual delay-line and a coincidence detection mechanism. This paper focuses on description of the noise cancellation stage. We designed a simple subtraction method which, when strategically employed over the dual delay line structure in the broadband manner, can effectively cancel multiple interfering sound sources and consequently enhance the desired signal. We obtained an 8-10 dB enhancement for the desired speech in the situations of four talkers in the anechoic acoustic test (or 7-10 dB enhancement in the situations of six talkers in the computer simulation) when all the sounds were equally intense and temporally aligned. PMID- 11785824 TI - Improvements in intelligibility of noisy reverberant speech using a binaural subband adaptive noise-cancellation processing scheme. AB - This article reports on the performance of an adaptive subband noise cancellation scheme, which performs binaural preprocessing of speech signals for a hearing-aid application. The multi-microphone subband adaptive (MMSBA) signal processing scheme uses the least mean squares (LMS) algorithm in frequency-limited subbands. The use of subbands enables a diverse processing mechanism to be employed, splitting the two-channel wide-band signal into smaller frequency-limited subbands, which can be processed according to their individual signal characteristics. The frequency delimiting used a linear- or cochlear-spaced subband distribution. The effect of the processing scheme on speech intelligibility was assessed in a trial involving 15 hearing-impaired volunteers with moderate sensorineural hearing loss. The acoustic material consisted of speech and speech-shaped noise signals, generated using simulated and real-room acoustic environments, at signal-to-noise ratios (SNRs) in the range -6 to +3 dB. The results show that the MMSBA scheme delivered average speech intelligibility improvements of 11.5%, with a maximum of 37.25%, in noisy reverberant conditions. There was no significant reduction in mean speech intelligibility due to processing, in any of the test conditions. PMID- 11785825 TI - Ultrasonic properties of random media under uniaxial loading. AB - Acoustic properties of two types of soft tissue-like media were measured as a function of compressive strain. Samples were subjected to uniaxial strains up to 40% along the axis of the transducer beam. Measurements were analyzed to test a common assumption made when using pulse-echo waveforms to track motion in soft tissues--that local properties of wave propagation and scattering are invariant under deformation. Violations of this assumption have implications for elasticity imaging procedures and could provide new opportunities for identifying the sources of backscatter in biological media such as breast parenchyma. We measured speeds of sound, attenuation coefficients, and echo spectra in compressed phantoms containing randomly positioned scatterers either stiffer or softer than the surrounding gelatin. Only the echo spectra of gel media with soft scatterers varied significantly during compression. Centroids of the echo spectra were found to be shifted to higher frequencies in proportion to the applied strain up to 10%, and increased monotonically up to 40% at a rate depending on the scatterer size. Centroid measurements were accurately modeled by assuming incoherent scattering from oblate spheroids with an eccentricity that increases with strain. While spectral shifts can be accurately modeled, recovery of lost echo coherence does not seem possible. Consequently, spectral variance during compression may ultimately limit the amount of strain that can be applied between two data fields in heterogeneous media such as lipid-filled tissues. It also appears to partially explain why strain images often produce greater echo decorrelation in tissues than in commonly used graphite-gelatin test phantoms. PMID- 11785826 TI - A point process approach to assess the frequency dependence of ultrasound backscattering by aggregating red blood cells. AB - To study the shear-thinning rheological behavior of blood, an acoustical measurement of the erythrocyte aggregation level can be obtained by analyzing the frequency dependence of ultrasonic backscattering from blood. However, the relation that exists among the variables describing the aggregation level and the backscattering coefficient needs to be better clarified. To achieve this purpose, a three-dimensional random model, the Neyman-Scott point process, is proposed to simulate red cell clustering in aggregative conditions at a low hematocrit (H<5%). The frequency dependence of the backscattering coefficient of blood, in non-Rayleigh conditions, is analytically derived from the model, as a function of the size distribution of the aggregates and of their mass fractal dimension. Quantitative predictions of the backscatter increase due to red cell aggregation are given. The parametric model of backscatter enables two descriptive indices of red cell aggregation to be extracted from experimental data, the packing factor W and the size factor delta. Previously published backscatter measurements from porcine whole blood at 4.5% hematocrit, in the frequency range of 3.5 MHz-12.5 MHz, are used to study the shear-rate dependence of these two indices. PMID- 11785827 TI - Differential degradation of antbird songs in a neotropical rainforest: adaptation to perch height? AB - Habitat characteristics that affect transmission and degradation of acoustical signals should influence strongly the evolution of bird songs. In this study propagation properties of songs of five antbird species were measured in a rainforest in southern Venezuela. The investigated species (Myrmothera campanisona, Thamnophilus aethiops, Thamnophilus amazonicus, Myrmotherula axillaris, and Herpsilochmus dorsimaculatus) use different song post heights at all levels of the rainforest. Because there is a height-specific pattern in degradation, it is hypothesized that their songs are adapted to species-specific transmission paths. To test this assumption, transmission parameters (excess attenuation, signal-to-noise ratio, and blur ratio) were measured for the songs at five different heights and at three different distances. In three of the five species, the results indicate a strong influence of environmental conditions on the design of the vocalizations. Degradation was minimized by the concentration of the signal to a narrower frequency range, the usage of lower frequencies, or a slower time structure for the songs near the ground. The results are discussed in relation to acoustical models of sound propagation and physiology, and it is suggested that height-dependent degradation within a forest is an important selection pressure for transmissibility in avian communication. PMID- 11785828 TI - Fundamental precision limitations for measurements of frequency dependence of backscatter: applications in tissue-mimicking phantoms and trabecular bone. AB - Various models for ultrasonic scattering from trabecular bone have been proposed. They may be evaluated to a certain extent by comparison with experimental measurements. In order to appreciate limitations of these comparisons, it is important to understand measurement precision. In this article, an approach proposed by Lizzi and co-workers is adapted to model precision of estimates of frequency-dependent backscatter for scattering targets (such as trabecular bone) that contain many scatterers per resolution cell. This approach predicts uncertainties in backscatter due to the random nature of the interference of echoes from individual scatterers as they are summed at the receiver. The model is validated in experiments on a soft-tissue-mimicking phantom and on 24 human calcaneus samples interrogated in vitro. It is found that while random interference effects only partially explain measured variations in the magnitude of backscatter, they are virtually entirely responsible for observed variations in the frequency dependence (exponent of a power law fit) of backscatter. PMID- 11785829 TI - Suppression of large intraluminal bubble expansion in shock wave lithotripsy without compromising stone comminution: methodology and in vitro experiments. AB - To reduce the potential of vascular injury without compromising the stone comminution capability of a Dornier HM-3 lithotripter, we have devised a method to suppress intraluminal bubble expansion via in situ pulse superposition. A thin shell ellipsoidal reflector insert was designed and fabricated to fit snugly into the original reflector of an HM-3 lithotripter. The inner surface of the reflector insert shares the same first focus with the original HM-3 reflector, but has its second focus located 5 mm proximal to the generator than that of the HM-3 reflector. With this modification, the original lithotripter shock wave is partitioned into a leading lithotripter pulse (peak positive pressure of 46 MPa and positive pulse duration of 1 micros at 24 kV) and an ensuing second compressive wave of 10 MPa peak pressure and 2 micros pulse duration, separated from each other by about 4 micros. Superposition of the two waves leads to a selective truncation of the trailing tensile component of the lithotripter shock wave, and consequently, a reduction in the maximum bubble expansion up to 41% compared to that produced by the original reflector. The pulse amplitude and -6 dB beam width of the leading lithotripter shock wave from the upgraded reflector at 24 kV are comparable to that produced by the original HM-3 reflector at 20 kV. At the lithotripter focus, while only about 30 shocks are needed to cause a rupture of a blood vessel phantom made of cellulose hollow fiber (i.d.=0.2 mm) using the original HM-3 reflector at 20 kV, no rupture could be produced after 200 shocks using the upgraded reflector at 24 kV. On the other hand, after 100 shocks the upgraded reflector at 24 kV can achieve a stone comminution efficiency of 22%, which is better than the 18% efficiency produced by the original reflector at 20 kV (p = 0.043). All together, it has been shown in vitro that the upgraded reflector can produce satisfactory stone comminution while significantly reducing the potential for vessel rupture in shock wave lithotripsy. PMID- 11785830 TI - Auditory display of knee-joint vibration signals. AB - Sounds generated due to rubbing of knee-joint surfaces may lead to a potential tool for noninvasive assessment of articular cartilage degeneration. In the work reported in the present paper, an attempt is made to perform computer-assisted auscultation of knee joints by auditory display (AD) of vibration signals (also known as vibroarthrographic or VAG signals) emitted during active movement of the leg. Two types of AD methods are considered: audification and sonification. In audification, the VAG signals are scaled in time and frequency using a time frequency distribution to facilitate aural analysis. In sonification, the instantaneous mean frequency and envelope of the VAG signals are derived and used to synthesize sounds that are expected to facilitate more accurate diagnosis than the original signals by improving their aural quality. Auditory classification experiments were performed by two orthopedic surgeons with 37 VAG signals including 19 normal and 18 abnormal cases. Sensitivity values (correct detection of abnormality) of 31%, 44%, and 83%, and overall classification accuracies of 53%, 40%, and 57% were obtained with the direct playback, audification, and sonification methods, respectively. The corresponding d' scores were estimated to be 1.10. -0.36, and 0.55. The high sensitivity of the sonification method indicates that the technique could lead to improved detection of knee-joint abnormalities; however, additional work is required to improve its specificity and achieve better overall performance. PMID- 11785831 TI - Three-dimensional modeling of hearing in Delphinus delphis. AB - Physical modeling is a fertile approach to investigating sound emission and reception (hearing) in marine mammals. A method for simulation of hearing was developed combining three-dimensional acoustic propagation and extrapolation techniques with a novel approach to modeling the acoustic parameters of mammalian tissues. Models of the forehead and lower jaw tissues of the common dolphin, Delphinus delphis, were created in order to simulate the biosonar emission and hearing processes. This paper outlines the methods used in the hearing simulations and offers observations concerning the mechanisms of acoustic reception in this dolphin based on model results. These results include: (1) The left and right mandibular fat bodies were found to channel sound incident from forward directions to the left and right tympanic bulla and to create sharp maxima against the lateral surfaces of each respective bulla; (2) The soft tissues of the lower jaw improved the forward directivity of the simulated receptivity patterns; (3) A focal property of the lower-jaw pan bones appeared to contribute to the creation of distinct forward receptivity peaks for each ear; (4) The reception patterns contained features that may correspond to lateral hearing pathways. A "fast" lens mechanism is proposed to explain the focal contribution of the pan bones in this dolphin. Similar techniques may be used to study hearing in other marine mammals. PMID- 11785832 TI - Numerical analysis of ultrasonic transmission and absorption of oblique plane waves through the human skull. AB - Ultrasonic transmission and absorption of oblique plane waves through the human skull are analyzed numerically for frequencies ranging from 1/2 to 1 MHz. These frequencies are optimum for noninvasive ultrasound therapy of brain disorders where numerical predictions of skull transmission are used to set the phase and amplitude of source elements in the phased array focusing system. The idealized model of the skull is a three-layer solid with ivory outer and inner layers and a middle marrow layer. Each layer is modeled as a flat, homogeneous, isotropic, linear solid with effective complex wave speeds to account for focused energy losses due to material damping and scattering. The model is used to predict the amplitude and phase of the transmitted wave and volumetric absorption. Results are reported for three different skull thicknesses: 3 mm, 6 mm, and 9 mm. Thickness resonances are observed in the transmitted wave for 3 mm skulls at all frequencies and for the 6 mm skulls below 0.75 MHz. Otherwise, the transmission is dominated by the direct wave. Skull phase errors due to shear waves are shown to minimally degrade the power at the focus for angles of incidence up to 20 degrees from normal even for low material damping. The location of the peak volumetric absorption occurs either in the outer ivory or middle marrow layer and shown to vary due to wave interference. PMID- 11785833 TI - Immunosurveillance, immunodeficiency and lymphoproliferations. AB - The incidence of malignant lymphomas is significantly higher in patients who have congenital or acquired immunodeficiencies. Although there are some differences between these immunodeficiency-associated lymphoproliferative disorders (IALD), they share several features: a tendency to present in extranodal sites, particularly the central nervous system and gastrointestinal tract, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the Epstein-Barr virus (EBV). In the presence of disturbed T cell function EBV may induce not only prolonged proliferation but also transformation of B-cells. In patients with primary, congenital immunodeficiency the incidence of IALD ranges from 0.7% for patients with X-linked agammaglobulinemia to 12-15% in patients with ataxia telangiectasia. In patients with post-transplant lymphoproliferative disorders (PT-LPD) the incidence varies from 0.5% after bone marrow transplantation to 10% after heart-lung transplantation. PT-LPD are often characterized by a polymorphic cell population. Recent studies identified three categories: plasmacytic hyperplasia, polymorphic lymphoproliferation and B-cell non-Hodgkin's lymphoma (NHL). The plasmacytic hyperplasias are of polyclonal composition, while polymorphic lymphoproliferations and NHL are monoclonal. The precise risk of lymphoma development in HIV infection is not defined, but estimates suggest a prevalence of 3-4%. HIV-related NHLs are divisible by site of manifestation into systemic, primary central nervous system and body-cavity lymphomas, and by pathology into Burkitt's and Burkitt's-like lymphoma, and diffuse large cell lymphoma (DLCL). In about 90% of cases these lymphomas are of monoclonal B-cell composition. Recent experiences suggest a link between therapy with immunosuppressive drugs (methotrexate, azathioprine, cyclophospamide, etc.) and development of IALD, best supported by the increased rate of IALD in patients with rheumatoid arthritis who receive methotrexate therapy. The occurrence of IALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too. PMID- 11785834 TI - Engineered antibody for treating lymphoma. AB - One approach to improving the results of antibody treatment of posttransplant and other lymphomas is to alter the geometry of the antibody molecule so as to enhance its cytotoxicity. When antibody alights on a cell, cytotoxicity can be exerted by initiation of apoptotic signals at the cell surface, and by recruitment of effectors to specific sites on the antibody Fc region. Other routes to cytotoxicity have been described but their generality is debatable. The effectors consist of complement, and a series of potentially cytotoxic cells (macrophages, NK cells, neutrophils and others) bearing Fc-receptors (FcR). Recent evidence suggests that the FcR-bearing cells are the more important in dealing with antibody-coated autologous cells, including tumor cells. If the antibody happens to be of the host IgG class then its Fc region (Fcgamma) will contain a site for attachment of a non-cytotoxic FcR known as FcRB (the Brambell receptor): it is this receptor, present on endothelial cells, which recycles the molecule intact if it happens to be endocytosed and thus prolongs its metabolic life. Replacement of the mouse Fcgamma by human Fcgamma is expected to have three beneficial effects: better recruitment of human effector cells, better persistence of the antibody in extracellular fluid, and removal of a major source of immunogenic epitopes. Chemical manipulations of Fab'gamma and Fcgamma modules, linking them in different geometries via their hinge regions, offers constructs with further enhancements of cytotoxicity. These include Fab2Fc2, in which the presence of dual Fc regions enhances recruitment of both complement and cellular effectors; and bispecific antibody of the same modular formula in which one of the Fab arms is specific for tumor while the other is specific for, and recruits powerfully, a cellular effector. PMID- 11785835 TI - Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies. AB - The treatment of post-transplant lymphomas still needs major improvements in order to put the patient in remission and to retain graft function. Chemotherapy is far too toxic in these patients. A more specific treatment such as anti-B-cell monoclonal antibody is very promising. The cytotoxic effect of antibody relies mainly on complement-induced and antibody-dependent cellular cytotoxicity; apoptosis may also induce tumor cell death. B-cell antigens expressed on the cell surface are the targets of antibody attack; some specificities may be chosen because of their level of expression or because of signaling induced within the cell. Anti-B-cell antibodies can be produced by genetic engineering in order to be humanized or to carry bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal antibodies (mAbs) in transplant patients have been proven with different antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb. In a retrospective analysis of different centers in France, rituximab (anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate in 34 organ and bone marrow transplant patients. But the conditions of use of antibody must be better defined, particularly with regard to the immunosuppressive therapy, the type of tumor and the dose of antibody. We must also improve our understanding of the in vivo mechanisms of action of antibody to develop more efficient antibody constructs. PMID- 11785836 TI - Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomas. AB - The Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) that occur in individuals immunosuppressed by solid organ transplant (SOT) or T cell depleted stem cell transplantation (SCT) are unequivocally a result of T cell dysfunction. Reconstitution of "at-risk" patients with EBV-specific cytotoxic T lymphocyte (CTL) lines that have been reactivated and expanded in vitro, should prevent the development of post-transplant lymphoproliferative disease or treat pre-existing disease. We have provided over 125 infusions of donor-derived EBV specific CTL to 60 recipients of T cell-depleted stem cells. As prophylaxis, infusions were safe and effective, as no patient developed EBV-LPD, in contrast to 11.5% of controls who did not receive CTL. The CTL-reconstituted cellular immune responses to EBV, persisted for up to 80 months following infusion and reduced the high virus load seen in about 12% of patients. CTL were also effective in two of three patients who received CTL as treatment for fulminant disease. SOT recipients are also good candidates for CTL therapy, but present problems not seen in bone marrow transplant recipients. First the CTL product must be autologous, since the majority of tumors are recipient-derived and allogeneic CTL are unlikely to survive in vivo. Second most patients continue to receive immunosuppressive drugs, which may compromise the function of infused CTL. Third, unlike SCT recipients SOT recipients do not have an empty niche for EBV-specific CTL. Finally, standard protocols are not effective in generating CTL from seronegative recipients of EBV-carrying organs, who are the patients most at risk for the development of EBV-LPD. For CTL to be an option for the management of EBV in these patients, a sensitive and specific assay for the prediction of high-risk patients is required as well as an effective method for the generation of EBV-specific CTL from seronegative recipients. PMID- 11785837 TI - Non-myeloablative stem cell transplantation for congenital immunodeficiencies. AB - Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital immunodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality. We have therefore used a low-intensity conditioning regime for transplantation in this group of immunodeficiency patients. Twenty-one patients with a variety of different immunodeficiencies were treated using the following conditioning regimes: (1) fludarabine/melphalan/ATG or Campath 1H (n=16), (2) fludarabine/cyclophosphamide/Campath 1H (n=1), (3) TBI/CyA/MMF (n=1), (4) fludarabine/melphalan/busulphan/ATG (n=3). In 13 cases matched (n=9) and 1 Ag mismatched (n=4) unrelated donors were used and in eight cases transplants from matched siblings (n=4), 1 Ag mismatched sibling (n=1), matched parent (n=1) and haploidentical parents (n=3) were performed. At a median follow-up of 13 months, 19 of 21 (90%) patients were still alive following the transplant procedure. Despite a T cell replete graft and the use of unrelated donor grafts in the majority of patients studied there was no evidence of significant organ disease. Immune reconstitution in terms of CD3+ and CD4+ T cell recovery and function was equivalent in comparison with a historical cohort. We believe that this low-intensity approach has significant implications for transplantation of individuals with immunodeficiency states with established organ disease. PMID- 11785838 TI - Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma. AB - Chemotherapy regimens similar to those used for non-Hodgkin's lymphoma (NHL) not associated with human immunodeficiency virus (HIV) infection have been used for patients with HIV-associated NHL with less success. In a recent trial, patients with intermediate or high-grade NHL were randomized to either low-dose chemotherapy with methotrexate, bleomycin, doxorubicin, vincristine and dexamethasone (m-BACOD) or to standard-dose m-BACOD with sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF). With low-dose m-BACOD 41% of patients achieved a complete remission and the median survival was 35 weeks. With standard-dose m-BACOD and sargramostim, the percentage of complete remissions was 52% with a median survival of 31 weeks (P=n.s.). Myelosuppression was greater with standard-dose chemotherapy. In univariate and multivariate analyses of 21 pretreatment features of patients in this trial, four factors emerged as adversely prognostic with respect to survival: age >35 years, intravenous drug use, CD4 counts < 100/mm3 and stage III/IV disease. In an analysis using the proportional hazards model, a "favorable" group was defined by patients with 0 or 1 adverse factor (median survival 46 weeks, survival at 144 weeks 29.5%) as compared with an unfavorable group with 3 or 4 adverse factors (median survival 18 weeks, survival at 144 weeks 0). The outcome of these patients may be improving with the use of highly active antiretroviral therapy (HAART), which seems to improve immune function and tolerance of chemotherapy. A recent trial of the AIDS Malignancy Consortium found that low-dose chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone: CHOP) and standard dose chemotherapy had similar response rates, acceptable toxicity and minimal alterations in cyclophosphamide, doxorubicin and indinavir pharmacokinetics in HIV-associated lymphoma patients also on HAART (stavudine, lamivudine and indinavir). There is a suggestion that Burkitt-type lymphomas may tend to occur in HIV-infected patients with relatively well preserved immune function and CD4 cell counts. Recent results from our institution suggest that similar outcomes are achievable with intensive chemotherapy in patients with Burkitt's lymphomas with or without HIV infection. With improved immune status and improved bone marrow function with the use of HAART, it will probably become more possible to treat many patients with aggressive HIV-associated NHL with more intensive treatment regimens. PMID- 11785839 TI - Infusional CDE with rituximab for the treatment of human immunodeficiency virus associated non-Hodgkin's lymphoma: preliminary results of a phase I/II study. AB - Infusional CDE (cyclophosphamide, doxorubicin, etoposide; iCDE) is one of the most effective chemotherapeutic regimen for human immunodeficiency virus (HIV) associated non-Hodgkin's lymphoma (NHL), with a complete remission rate of 46% and a median overall survival of 8.2 months (Sparano JA, Blood 1993; 81:2810). Since the majority of HIV-associated NHL are CD20-positive we reasoned that the addition of rituximab to iCDE (R-iCDE) could also improve the poor outcome of these patients. As a first step we investigated the safety of R-iCDE in a phase I/II study. Thirty patients with aggressive HIV-associated NHL were enrolled between June 1998 and October 2000. Characteristics of 29 evaluable patients were: median age: 38 years (range 29-65 years); male sex 24/29; histology: DLCL 16 (55%), Burkitt 10 (35%), ALCL 2 (7%), unclassified 1 (3%); stage: I (35%), II (10%), III (10%), IV (45%); International Prognostic Index: 0, 1 (59%), 2 (24%), 3 (17%), 4, 5 (0); CD4 count: median 132/ mm3 (range 3-470/mm3). Patients received rituximab (375 mg/m2) in conjunction with iCDE (five or six cycles). All patients were treated with G-CSF and highly active antiretroviral therapy (HAART). Twenty-six of 29 patients received treatment as planned, while chemotherapy had to be discontinued in three patients (2 persistent thrombocytopenias, 1 cerebral hemorrhage). Grade 3 or 4 toxicity was observed as follows: neutropenia 79%, anemia 45%, thrombocytopenia 34%, bacterial infection 34%, opportunistic infection 7%, mucositis 17%. A dose reduction was necessary in 22%. Complete remission was achieved in 86% of the patients, partial remission in 4%. Ten percent had progressive disease. After a median follow-up of 9 months the median overall survival is not reached. The actuarial survival at 2 years is 80% and the actuarial progression-free survival is 79%. Four of 29 patients (14%) have died, three from NHL and one from cryptosporidiosis. These findings suggest that the combination of rituximab with iCDE in patients with HIV-associated NHL is safe and feasible and that the addition of the anti-CD20 antibody does not increase the risk for infections. The high complete remission rate also indicates a potential therapeutic benefit and warrants further randomized trials. PMID- 11785840 TI - Iatrogenic lymphoproliferative disorders in non-transplantation settings. AB - Over the last decade, it has become clear that iatrogenic immunodeficiency related lymphoproliferative disorders can occur in non-transplantation settings. These lymphoproliferative disorders occur predominantly in patients with rheumatologic diseases who are treated with immunomodulatory drugs. Like immunodeficiency-related lymphoproliferations in other settings, these represent a spectrum of lymphoid neoplasms and are frequently associated with Epstein-Barr virus. The distribution of histologic types of iatrogenic lymphoproliferations in non-transplantation settings appears to differ from that seen in other immunodeficiency settings with a probable increase in representation of Hodgkin's disease and lymphoproliferations resembling Hodgkin's disease. Recognition of these immunodeficiency-related lymphoproliferative disorders is important for appropriate patient management. PMID- 11785841 TI - The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. AB - The Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is found invariably in Kaposi's sarcoma, and compelling evidence suggests that it is an etiologic agent for this disease. KSHV has also been found to be present in a limited subset of lymphoproliferative disorders. Among these are the primary effusion lymphomas, formerly designated body cavity-based lymphomas. This is a rare type of malignant lymphoma which possesses an unusual set of clinical and biologic features, suggesting that it represents a distinct disease entity. This virus is also present in a large proportion of cases of multicentric Castleman's disease, particularly those associated with HIV infection. In addition, KSHV has been implicated in the pathogenesis of multiple myeloma, but many laboratories including our own have been unable to confirm this association. KSHV carries at least 11 open reading frames (ORFs) that encode homologs to cellular proteins involved in signal transduction, cell cycle regulation, inhibition of apoptosis and/or immune modulation. Therefore, it has the genetic machinery of an oncogenic virus. However, only a small proportion of infected people ever develop Kaposi's sarcoma or virus-induced lymphoma, and do so only after a long latency period. This observation reflects the multistep nature of oncogenesis, with viral infection representing only one of these steps. Cofactors such as HIV infection and iatrogenic immunosuppression dramatically increase the risk for developing a KSHV-related malignancy in infected individuals. Understanding the oncogenic and immunologic mechanisms involved in the pathobiology of virus-associated lymphomas is important for the development of targeted therapeutic and preventive approaches. PMID- 11785842 TI - Dendritic cells for the induction of EBV immunity. AB - Cell-mediated immunity provides resistance to Epstein-Barr virus (EBV), as demonstrated by the occurrence of EBV-induced post-transplant lymphoproliferative disease (PTLPD) in immunosuppressed patients. T cell immunity is stimulated most effectively by dendritic cells (DCs). Although DCs are not direct targets for infection by EBV, we tested whether EBV antigens are cross-presented by human DCs and whether DCs are efficient at stimulation of EBV-specific CD8+ T cells. We show that DCs cross-presenting apoptotic or necrotic lymphoblastoid cell lines (LCLs) are able to expand CD8+ T cells that directly recognize HLA-matched LCLs by IFN-gamma secretion and cytolytic activity. Part of this EBV-specific CD8+ T cell response was specific for the EBV nuclear antigen EBNA3 A and the latent membrane protein LMP2a. Both these antigens are expressed in PTLPD. In other EBV associated malignancies such as Hodgkin' s lymphoma, T cell lymphoma and nasopharyngeal carcinoma, LMP2a is maintained. Therefore, the cross-presenting ability of DCs might be explored in DC-mediated active immunization against EBV associated malignancies. PMID- 11785843 TI - NF-kappaB inhibition in EBV-transformed lymphoblastoid cell lines. AB - Epstein-Barr virus (EBV) transforms B-lymphocytes into lymphoblastoid cell lines usurping multiple signaling pathways including NF-kappaB activation. To determine whether NF-kappaB activity is essential in the growth and survival of EBV transformed lymphoblastoid cell lines, a non-degradable IkappaBa mutant was expressed under tetracycline regulation in IB4 cells. NF-kappaB inhibition caused caspase 3 and 8 activation, PARP cleavage, and DNA fragmentation indicative of apoptosis. Mitochondrial membrane potential was diminished without release of cytochrome c or apoptosis initiating factor. z-VAD.FMK, a general caspase inhibitor, failed to block apoptosis, indicating a distinct pathway contributes to cell death. Bfl-1 expression, an anti-apoptotic Bcl-2 family member, is diminished after NF-kappaB inhibition whereas Bcl-2 and Bcl-x/L expression is unaffected. These studies suggest that NF-kappaB itself, or NF-kappaB-regulated genes, will be successful molecular targets for the treatment of EBV-associated diseases. PMID- 11785844 TI - Epstein-Barr viral load as a tool to diagnose and monitor post-transplant lymphoproliferative disease. AB - Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disease (PTLD) continues to be a rare but severe complication following transplantation. EBV viral load is used as a tool to identify patients at risk for developing PTLD. However, studies on EBV viral load are hard to compare since study design as well as EBV detection method and calculation of results are highly variable. In the majority of cases EBV viral load is increased in patients with PTLD compared to patients without disease. There is, however, some overlap. Some individual patients with only low viral load show PTLD while others show the opposite. The major future goals will be to standardize EBV-DNA detection in order to generate comparable data in different centers and to establish cut-off values to distinguish patients with PTLD from patients without with a high precision. PMID- 11785845 TI - The role of immunosuppression in lymphoma. AB - Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients and currently represents the second most common de novo malignancy following solid organ transplantation. PTLD has been noted in all transplant immunosuppressive eras including the pre-cyclosporine, cyclosporine, and post-cyclosporine eras. The time from organ transplantation to PTLD presentation varies widely from less than 1 month to several years. PTLD presents with a broad spectrum of clinical manifestations depending on the transplanted organ, immunosuppressive therapy and patient age. Intense immunosuppressive therapy is a major risk factor for development of PTLD. Whenever a new agent is introduced, there is a learning curve that leads to dosing modifications, which in turn result in optimization of its immunosuppressive efficacy and reduction of toxicities, including PTLD. We review the major historical and recent immunosuppression trials to assess the impact of individual immunosuppressive agents and regimens on PTLD risk. PMID- 11785846 TI - Identification of prognostic factors in post-transplant lymphoproliferative disorders. AB - Organ transplantations can lead to post-transplant lymphoproliferative disorders (PT-LPDs) as a result of immunosuppressive therapy. PT-LPDs clearly differ from non-Hodgkin's lymphomas occurring in immunocompetent patients, in terms of clinical presentation, pathological findings and treatment response. Several studies have tried to establish some prognostic factors but the small number of patients hinders the analysis. We studied 61 patients from two transplant centers who developed a PT-LPD after kidney (34 patients), heart (19 patients), lung (4 patients) or liver (3 patients) transplantation. Treatment consisted of modification of the immunosuppressive regimen, chemotherapy and/or monoclonal antibody infusions. Analyzing potential prognostic factors, we found that factors predictive of failure to achieve a complete remission were, in univariate analysis, a performance status (PS) > or =2 and negativity of the tumor for the Epstein-Barr virus (EBV), and in multivariate analysis, only the PS. Factors predictive of lower survival were, in univariate analysis, a PS > or =2, number of sites > 1, primary central nervous system (CNS) location, T-cell phenotype, monoclonality of the tumor, tumor negativity for EBV and chemotherapy as a first treatment; in multivariate analysis, only PS and the number of sites were statistically significant. The International Prognostic Index (IPI) failed to identify a patient subgroup with a lower survival or treatment response, whereas a simple index using PS and number of sites clearly identified three different groups. The median survival has not yet been reached in the lower-risk group, whereas it is 34 months in the intermediate-risk patients and 1 month in the high risk group. Studies on larger cohorts of patients need to be performed to confirm these data. PMID- 11785847 TI - Methods and objectives of a large US multicenter case-control study of post transplant lymphoproliferative disorder in renal transplant patients. AB - A large multicenter case-control study is in progress in the United States, the primary goal of which is to provide information about the effects of specific immunosuppressants and other risk factors on posttransplant lymphoproliferative disorder (PTLD) in renal transplant patients. It will also provide incidence data and case characterization on PTLDs arising in a large contemporary population. Medical record data are being collected on up to 120 PTLD cases and up to four controls per case transplanted at 20 large US centers. Participants all received transplants on or after July 1, 1995 and PTLD cases will be identified through December 31, 2001. All cases undergo central clinical and pathologic review. Abstracted information includes detailed data (dosages, duration) on all immunosuppressants (induction, maintenance, anti-rejection) as well as antiviral treatment. Other data include demographics, transplant history, HLA matching and viral status (e.g., Epstein-Barr virus, cytomegalovirus). Information associated with the PTLD diagnosis and initial therapy for PTLD is also collected. To date, 86 potential cases have been reported. Twenty (24%) are pediatric patients (< or =18 years). Median time between transplant and PTLD is 268 days; 53 (62%) were diagnosed within the first year. Cumulative incidence through 1998 is 0.7% for adults and 4.5% for children. The most common single site for PTLD is the allograft. Common treatments included either a reduction or discontinuation of immunosuppression (90%) and antiviral treatment (66%). Overall, the allograft appears to be an important site of PTLD recurrence. Also, the incidence of renal PTLD since the introduction of new immunosuppressive therapies is similar to that reported earlier. PMID- 11785848 TI - Antiviral treatment of Epstein-Barr virus-associated lymphoproliferations. AB - Epstein-Barr virus (EBV)-associated lymphoproliferations may arise in individuals with hereditary or acquired immunodeficiencies. T-cell dysfunction and resulting insufficient control of EBV infection is common to all these patients in whom EBV associated lymphoproliferations develop. EBV is an oncogenic virus which induces proliferation and transformation of B-lymphocytes. Antiviral treatment may represent a causal treatment option with relatively low toxicity. Among the different antiviral drugs aciclovir and ganciclovir are not the drugs of choice, because in EBV-associated lymphoproliferations the viral thymidine kinase enzyme is not encoded regularly. The agent arginine butyrate has the ability to selectively activate EBV thymidine kinase genes in EBV-infected lymphoma cells. In combination with ganciclovir it has demonstrated efficacy in patients with EBV associated lymphoproliferations after solid organ transplantation. The action of foscarnet, another antiviral agent, is directed against the viral DNA, independent of the presence of the viral thymidine kinase. In our experience treatment with foscarnet resulted in continuous complete remissions in patients with EBV-associated lymphoproliferations. These clinical experiences demonstrate the efficacy of antiviral treatment in EBV-associated lymphoproliferations. PMID- 11785849 TI - Clinicopathologic characteristics of post-transplant lymphoproliferative disorders. AB - Post-transplant lymphoproliferative disorder (PTLD) is a syndrome of uncontrolled lymphoid growth in the immunosuppressed transplant patient. Known risk factors include Epstein-Barr virus (EBV) seronegativity at the time of transplant, pediatric age and allograft type. Newer studies suggest that constitutional factors such as cytokine gene polymorphisms may also predispose to PTLD. Although PTLD may occur at any time, the majority of cases arise within the first two post transplant years. Clinical presentation is heterogeneous and dependent upon the location and extent of disease. Allograft involvement is common, particularly in cases of lung, intestine, or pancreas transplantation. Most PTLD are of B lymphocyte origin. A histopathologic classification system has been proposed and it is important to understand the histology of these lesions, since the term PTLD incorporates both hyperplastic and neoplastic growths. Histologic subclassification also has prognostic value, although this remains imperfect at present. Clinical evaluation should include staging as for lymphomas, since PTLD stage is an important determinant of outcome. In EBV-associated PTLD, quantitative evaluation of EB viral genomic load has a role in guiding prophylaxis, diagnosis, and monitoring of therapy. The presence of EBV is not an absolute requirement for the diagnosis of PTLD, and it has been suggested that there has been a recent increase in the number of EBV-negative cases. Such lesions have a median onset time around 50-60 months post-transplant. Therapy of PTLD must be tailored to the individual patient. Newer modalities such as anti CD20 antibodies are being evaluated and may complement the standard stepwise approach that begins with a reduction of immunosuppression. The role of chemotherapy continues to be defined, and in some cases early recourse to this approach may be desirable. Survival varies by age and extent of disease, with pediatric patients and those with localized disease tending to fare better. A finer understanding of the molecular cellular and virologic underpinnings of PTLD remains essential in order to define optimal treatment regimens. The emergence of EBV-negative PTLD is a problem and the relationship of this to standard lymphomas arising in nonimmunosuppressed patients remains to be defined. Continued individual and multi-institutional studies are essential for progress in these areas. PMID- 11785850 TI - Low-dose chemotherapy for children with post-transplant lymphoproliferative disease. AB - Children are at higher risk for developing post-transplant lymphoproliferative disease (PTLD) than adults. Successful treatment of PTLD following solid organ transplant is a therapeutic challenge due to the patients' increased toxicity from chemotherapy, increased susceptibility to life-threatening infections, and the necessity to maintain the allograft. Patients who do not tolerate reduction of immune suppression (i.e., graft rejection), or have PTLD that does not respond to immune suppression reduction, require more aggressive therapy and have a much poorer prognosis. We report 39 children with PTLD who failed reduction of immune suppression and were treated with a low-dose chemotherapy regimen of cyclophosphamide (600 mg/m2) and prednisone (2 mg/kg per day for 5 days) given every 3 weeks for 6 cycles. The complete remission rate was 82%. Graft survival was 90%. Relapse rate was 22%, with late-onset PTLD (> or =2 years from transplant) more likely to relapse. Of the seven patients with relapsed PTLD, four were salvaged with "conventional" non-Hodgkin's lymphoma chemotherapy. The overall 1-year survival for patients treated with low-dose chemotherapy was 86%. The estimated 2-year survival is 73%. This low-dose chemotherapy approach is well tolerated and effective for PTLD in children who fail reduction of immune suppression. PMID- 11785851 TI - Predicting antibacterial response from pharmacodynamic and pharmacokinetic profiles. AB - The aim of antibacterial chemotherapy is to achieve sufficient drug concentrations at the site of infection for an adequate length of time to ensure bacterial eradication and optimize clinical success. Whether the desired outcome is achieved or not depends on a number of pathogen-, drug- and patient-related factors. Neither microbiologic activity nor antibacterial pharmacokinetic data alone can adequately describe the complex interaction between pathogen, host and antibacterial during the disease process. A relatively new discipline - pharmacodynamics - seeks to integrate both microbiologic and pharmacokinetic data. The particular model that best predicts clinical outcome depends on the pattern of microbial killing and the persistence of antibacterial effects after plasma concentrations have fallen below the minimum inhibitory concentration (MIC) for the target pathogen (post-antibiotic effect [PAE]). The beta-lactams, for example, exhibit time-dependent bacterial killing with minimal persistent effects. Time above MIC (T(MIC)) is therefore the parameter that best correlates with clinical efficacy for these agents and that, in turn, necessitates multiple daily dosing to optimize the duration of exposure. The macrolides erythromycinA and clarithromycin exhibit a similar pharmacokinetic/pharmacodynamic relationship to that of the beta-lactams, although for clarithromycin the area under the concentration-time curve (AUC) also correlates with clinical outcome (reflecting the more prolonged PAE of this agent). Azithromycin, ketolides, such as telithromycin (HMR 3647), streptogramins and fluoroquinolones exhibit concentration-dependent killing and have prolonged persistent effects, such that the AUC:MIC or Cmax:MIC ratio correlates most closely with clinical efficacy. For these agents the aim is to maximize drug concentrations to which the target pathogen is exposed and this may require higher doses and hence enable longer dosing intervals to be used. In summary, pharmacodynamic models provide a unique approach to determining likely in vivo activity of individual antibacterial agents and prediction of clinical outcomes. PMID- 11785852 TI - Clinical management of respiratory tract infections in the community: experience with telithromycin. AB - Among adults, acute sinusitis, tonsillitis/pharyngitis, community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are the most commonly encountered respiratory tract infections (RTIs) in the community. Empiric antibacterial therapy is the most widely used approach for the treatment of such infections. The appropriate antibacterial requires consideration of a number of patient-, pathogen- and drug-related factors. One additional factor is the global spread of resistance among common respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, which limits the utility of existing antibacterials. Telithromycin (HMR 3647), the first of a new family of antibacterials, the ketolides, was designed specifically to provide optimal therapy for community-acquired RTIs. This agent, which has a broad spectrum of antibacterial activity against common respiratory pathogens (including resistant strains and atypical/intracellular organisms), has been clinically and bacteriologically evaluated against gold-standard comparators in a series of phase III clinical trials. The results of these studies demonstrate that telithromycin, at a dosage of 800 mg once daily, is an effective, well tolerated agent for the treatment of the most commonly encountered community acquired RTIs. Moreover, telithromycin meets the challenge of increasing antibacterial resistance. High rates of clinical cure and bacteriologic eradication were achieved, even in patients infected with problematic resistant pathogens such as penicillinG- and macrolide-resistant S. pneumoniae. In summary, telithromycin represents a promising new antibacterial for the treatment of community-acquired RTIs. With high efficacy and bacterial eradication rates, good tolerability and convenient once-daily administration, telithromycin therapy should result in increased patient compliance and improved outcomes, thereby minimizing the risk of developing antibacterial resistance. PMID- 11785853 TI - Barriers to the effective management of respiratory tract infections in the community. AB - The treatment of respiratory tract infections (RTIs) continues to challenge the knowledgeable and conscientious physician. Upper RTIs such as sinusitis and tonsillitis/pharyngitis - while not generally life-threatening - are associated with personal cost and suffering, while infections of the lower respiratory tract, including community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB), represent a more serious clinical challenge and account for almost half of all community-acquired infections. Moreover, such infections may be fatal. Laboratory tests for etiologic agents of RTIs are often insensitive and slow and identify the causative pathogen in only a minority of cases. Therapy for RTIs is, therefore, generally presumptive and instituted before there is a clear understanding of etiology. Such an approach requires antibacterials that possess a spectrum of activity which covers both the common and atypical/intracellular pathogens associated with RTIs to enable physicians to confidently prescribe treatment. A major barrier to the confident prescribing of empiric therapies for RTIs is the increasing prevalence of resistance to existing antibacterial agents among respiratory tract pathogens. Increasing levels of antibacterial resistance now threaten the utility of existing agents, primarily the beta-lactams and macrolides, and continue to drive the search for newer agents which retain activity against drug-resistant respiratory tract pathogens. This need is emphasized by recent evidence that bacterial resistance may be associated with poorer clinical outcomes, particularly for patients with severe infections. There is enormous concern and uncertainty about the factors that contribute to increasing bacterial resistance and treatment strategies that should be adopted to minimize this problem. The arguments have raged particularly around recent Infectious Diseases Society of America (IDSA) guidelines on the treatment of CAP, which have advocated a greater role for fluoroquinolones. One school of thought - driven in part by concerns over cost of therapy - advocates the use of older agents such as amoxicillin, in the hope that any resistance that is incurred will be to these agents, leaving the newer agents for select cases with acquired resistance. Advocates of the newer agents argue that this approach represents a false economy and that there is a greater likelihood of first-line success with newer agents, so that patients are less likely to require a second physician visit and a second course of antibacterial therapy. PMID- 11785854 TI - Changes and tracking of physical activity across seven years in Mexican-American and European-American mothers. AB - Longitudinal changes in physical activity among 129 Mexican-American (mean age 30.8; SD = 5.6) and 97 European-American (mean age 31.2; SD = 5.4) women were studied. Two physical activity recall interviews were administered at baseline and 7 years later. At baseline, European-American women reported more vigorous leisure activity (p < .005) than Mexican-Americans, and Mexican-Americans reported more moderate work activity (p < .02) than European-Americans. Virtually all components of physical activity increased significantly over the 7 years. Pearson tracking correlations for total energy expenditure were about r = 0.30. The finding that both groups increased physical activity overtime was unexpected and was unrelated to a reduction in the number of preschool children in the homes over time. PMID- 11785855 TI - Non-primary care physicians and smoking cessation counseling: Women Physicians' Health Study. AB - OBJECTIVES: The Women Physicians' Health Study (WPHS) offers a unique opportunity to examine the counseling and screening practices of women physicians in various specialties. In this study we describe the prevalence of self-reported counseling on smoking cessation among non-primary care women physicians and examine the association between their demographic, professional, and personal characteristics and such counseling on smoking cessation. METHODS: Conducted in 1993-1994, WPHS is a nationally representative cross-sectional mailed survey of U.S. women physicians with 4,501 respondents representing all major specialties. Physicians in 9 specialty areas were grouped in 6 categories: (1) anesthesiology; (2) general surgery and surgical subspecialties; (3) emergency medicine; (4) medical subspecialties; (5) psychiatry; and (6) other. Frequent counseling was defined as having counseled patients who were known smokers at every visit or at least once a year. RESULTS: Overall, 45% of the physicians frequently counseled smokers to quit. Medical subspecialists (80%) were most likely and psychiatrists (29%) least likely to counsel frequently. Specialty, perceived relevance of counseling to the physician's practice, and self-confidence in counseling about smoking cessation were associated with frequent counseling. CONCLUSION: Cessation counseling by non primary care physicians can reduce tobacco-related morbidity and mortality. Increasing perceived relevance and self-confidence among this group of physicians, combined with implementation of system changes and the creation of physician accountability can facilitate the provision of such counseling. PMID- 11785856 TI - Child and adolescent sexual abuse history in a sample of 1,490 women sexual partners of injection drug-using men. AB - Subjects for this study were 1490 community-recruited women sexual partners of injection drug-using men who were interviewed in three U.S. cities during 1990 '92. Data were collected on respondents' childhood and adolescent sexual abuse history, identity of abuse perpetrators and duration of abuse. Over 56 percent of respondents reported a history of sexual victimization by age 18, including 39 percent who were abused before age 12 and over 53 percent who were victimized by abuse involving bodily contact by age 18. One in three women were victimized by unwanted penetration by age 18. White women more likely than African-American and Hispanic women to have been the victims of virtually every type of abusive act investigated here. Overall, nearly two out of three White women had experienced some form of sexual abuse by age 18, including almost 42 percent who were the victims of unwanted penetration by this age. Acts of forced sexual touching and penetration occurring in childhood were most likely to have been carried out by an uncle or other relative of the victim; family members were much less likely to be the perpetrators of adolescent contact abuse. Based on these findings, it appears that many in this special population of women are likely to be at substantial risk for some of the long-term effects of early life sexual abuse, including those that may reduce victims' ability to take preventive action against HIV risk. Recommendations are offered for those who function as caregivers to this population, including drug treatment personnel. PMID- 11785857 TI - Variability in physician management of employment during pregnancy. AB - BACKGROUND AND OBJECTIVES: Successful employment outcomes for pregnant women result from a complex interplay between the woman, her employer, her prenatal care provider, laws and other influences. METHODS: A mail survey about management of employment during pregnancy was sent to directors of US residency programs that train prenatal care providers. Each physician was randomly assigned one of 4 vignette patients whose job involved prolonged standing, rotating shifts and lifting 40 lbs. Half the vignette patients had risk factors for preterm birth and half would have financial difficulty if placed on an unpaid antenatal leave. RESULTS: The 301 respondents estimated that they provide a written job restriction for 20% of their employed pregnant patients, although in 6 clinics the job restriction rate was 100%. For vignettes with preterm birth risk factors, 62.5% of physicians would always recommend a job restriction, 35.6% would do so sometimes, and 2.2% would rarely do so. When the vignette did not have risk factors for preterm birth, 21.5% of the physicians would always recommend a job restriction, 51.3% would do so sometimes, 25.9% would do so rarely and 1.3% would never do so. Economic factors were not associated with prescribing job restrictions. One in 5 of the residency programs provides no teaching on occupational health issues in pregnancy, and 65.1% provide 2 hours or less. CONCLUSIONS: Variability in employment recommendations suggests that some women may not obtain the job modifications that they need, whereas others may be restricted unnecessarily. The limited curriculum time devoted to this topic may make it difficult to train physicians about complex employment issues during pregnancy. PMID- 11785858 TI - Gender awareness among Veterans Administration health-care workers: existing strengths and areas for improvement. AB - In response to the growing number of women within the Veterans Health Administration (VHA), along with the challenge of meeting their health-care needs in a historically male-focused setting, VHA has supported a variety of research projects aimed at evaluating and improving the status of women's health and health-care experiences. While these efforts have primarily focused on aspects of care such as the availability and accessibility of services and the provision of timely care, this study focused on the contribution of interpersonal aspects of care. Specifically, staff gender awareness, conceptualized as health-care workers' gender-role ideology or attitudes, gender sensitivity, and knowledge was examined. Findings revealed both strengths and weaknesses in domains of staff gender awareness and significant relationships between staff demographics and gender awareness components. PMID- 11785859 TI - Blood and milk: constructions of female bodily fluids in Western society. AB - This paper explores ways in which these essentially 'female' bodily fluids are constructed in Western societies. It first reviews the context of menstruation and lactation in modern Western societies. It next considers menstruation and breastfeeding as affirmations of womanhood, and then the extent to which breast milk and menstrual blood are considered 'good,' 'different' to other milk and blood, sexual and disgusting. Finally, it discusses pressures which arise from the marketing of related products. The paper suggests that women's belief in their ability to nourish their infant from their own body may be undermined by negative constructions of women's bodily fluids which 'product'-based promotion of breast milk may fail to address. PMID- 11785860 TI - Interviewing men on sensitive issues. AB - The body alterations of men with prostate cancer affect their sexual functioning and raise common issues for men with this disease. This study examines these issues with the use of in-depth interviewing to collect sensitive data. The intention here is not to report the findings of the main study but to discuss broad methodological and practical issues raised by the research method of in depth interviewing. Interviews were conducted with 30 men with prostate cancer and it was found that access, sensitivity of the research topic, the environment and a number of psychological factors profoundly affected the interview process. The researcher's position in the study is that of the interviewer but she is also a nurse by profession. The findings will have implications for future studies which utilise in-depth interviewing as a research method to collect sensitive data. PMID- 11785861 TI - A proactive approach to assessing men for eating disorders. AB - Assessment guidelines for nurses on the subject of eating disorders (EDs) focus primarily on evaluating the severity and progress of the problem for females who have already received a formal ED diagnosis. We argue that, because there is scant research into men with eating disorders and men strive to conceal this health problem, nurses should be equipped with information that will support earlier detection of EDs among men and boys before they manifest as a serious health problem. We advocate the use of epidemiological data to identify groups of men most at risk and the use of qualitative interview data as a means of grounding the nurse on the issues these men face when seeking to modify their body image. PMID- 11785862 TI - The Papanicolaou test: its utility and efficacy in cancer detection. AB - The Papanicolaou (PAP) test is one of the simplest tests in the detection of cancer. This article addresses the concerns/fears women have surrounding the PAP test and why it is not more widely used. PMID- 11785863 TI - How can we argue for evidence in nursing? PMID- 11785864 TI - Patient education and the prevention of incisional hernia. AB - Laparoscopic or 'key hole' surgery has become an acceptable technique for abdominal surgery. This technique is utilised by surgeons who work in tertiary hospitals as well as those in private, day only, surgical facilities. Despite the increasing use of this technique in Australia, a paucity of information is available in the journals about the real or potential complications the patient may suffer following this method of surgery. The first author of this paper who works in the operating room practice domain, observed over three years a number of patients readmitted for repair of incisional hernia following abdominal laparoscopic surgery. A review of the international literature and dialogue with operating nurses from institutions in Sydney and Hong Kong confirmed there was enough evidence to warrant examining the complication of incisional hernia as a clinical problem. It would appear from the literature that incidence rate is unknown in Australia. Several reasons may account for this. First, it appears that few surgeons are documenting patient outcomes of laparoscopic surgery, not withstanding the proliferation of its use in the last five years. The second possible reason is the paucity of published information available in the journals, perhaps because the technique is still viewed as relatively new and experimental. This paper outlines a brief history of laparoscopic surgery and some responsibilities nurses have in relation to patient education and the prevention of post-operative complications. PMID- 11785865 TI - A comparison of medication errors between two storage sites. AB - This prospective single-blinded study aimed to compare the types of medication errors and medication error rates of two medication delivery systems. The setting was a 30 bed surgical ward that was divided into two identical areas. In one area medications were stored and issued in a ward bay workstation immediately outside the patients' rooms. The alternate area used a medication trolley at the patients' bedside. Three hundred and forty opportunities for errors were observed using five nurse educators. Twenty administration errors (5.8% error rate) and two dispensing errors (0.6% error rate) were detected. A statistically significant difference was found between the two systems, where four errors occurred from the medication trolley (2.6% error rate), and fifteen errors occurred from the ward bay (9.2% error rate). These results suggest that medications were less likely to be omitted and more likely to be given on time when they were issued at the patient's bedside using the medication trolley. PMID- 11785866 TI - Clinical supervision UK style: good for nurses and nursing? AB - British nursing has presented a particular view of clinical supervision and has made its availability an essential requirement for all nurses in the United Kingdom (UK). Through a plethora of literature, this view of clinical supervision has become widespread, as has the notion that it is good for nurses and nursing. In this paper, utilising a Foucauldian approach to discourse, power-knowledge and clinical gaze, I radically interrogate this seemingly unproblematic conceptualisation of clinical supervision and its rising popularity and influence. PMID- 11785867 TI - Burnout: results of an empirical study of New Zealand nurses. AB - Burnout is conceptualised as a syndrome consisting of three components-emotional exhaustion, reduced personal accomplishment and depersonalisation of clients or patients that occurs in individuals who work in the human service professions, particularly nursing. It has been observed that nurses are at a high risk of burnout and burnout has been described as the 'professional cancer' of nursing. This is the first New Zealand study to use the Maslach Burnout Inventory (MBI) and the Phase Model of Burnout to determine the extent and severity of burnout in a population of 1134 nurses. Results revealed an overall 'low to average' level of burnout, suggesting that New Zealand nurses, apart from those in the 41-45 age group, are doing better than expected insofar as they are managing to avoid or not progress to the advanced phases of burnout. Possible explanations and directions for future research are presented. PMID- 11785868 TI - The enculturation of our nursing graduates. AB - The transition from undergraduate nursing student to employment as a registered nurse is fraught with difficulties for a neophyte. This qualitative study used interviews and focus groups with graduate nurses from the Flinders University of South Australia in their first year of practice to ascertain their experiences as new graduates. The results reveal an enculturation of graduates not conducive to ongoing learning, consolidation of skills and application to practice. A rushed environment that was unpredictable, together with a lack of support, were recurrent themes from the graduates' perspective. Graduate nurse programs are run by institutions focused on outcomes and expenditure. There is little or no collaboration with the tertiary sector in providing appropriate programs according to graduates' needs. The graduates, as beginning practitioners, focused on not having the time to nurse holistically, an unrealistic workload, and the need for backup and continuous support on an individual basis. The wards, although possibly efficient and effective in providing health care, provided a culture where the graduates felt inadequate, rushed, overworked and unsupported, which is contrary to the aims and objectives of the graduate nurse programs. The nursing profession as a whole needs to develop a culture that is nurturing, enabling, supportive and protective of our young. PMID- 11785869 TI - Evidence and leadership: the tools for change. AB - Evidence based practice is seen to be a vehicle through which nurses can deliver more cost-effective care and improve patient outcomes. Despite this, however, 'evidence' does not always appear to influence policy and practice. Routine and traditional practices such as pre-operative fasting protocols seem particulary resistant to change. The research literature which repeatedly argues for reduced pre-operative fasting periods or clear fluids dates back to the 1800s. Current research indicates that the ingestion of clear fluids is safe two to four hours pre-operatively. Despite this evidence, however, pre-operative fasting for clear fluids, even for healthy young adults undergoing elective surgery, still persist for periods of up to twelve hours' duration. 'Evidence' was used in a surgical unit in a private hospital in Sydney to reduce pre-operative clear fluid fasting periods for patients requiring elective bowel surgery. This paper will describe the process of implementation of the reduced fasting guidelines. More specifiically, it will detail what was done and how it was done; it will also demonstrate the crucial role of strong nursing leadership in this evidence based change to existing practice. PMID- 11785870 TI - Coping strategies in clinical practice: the nursing students' lived experience. AB - This phenomenological study was designed to understand the lived experience of nursing students coping with the demands of their clinical practice. The Husserlian phenomenological approach was used. The data revealed several strategies that fourteen student nurses utilised to cope with the demands of their undergraduate clinical program. The participants discussed having a strong determination to complete their course and talking things over with family, friends, and other students as means of helping them get through it. They considered that only other nursing students could really understand the experience of being a student nurse. Therefore, a very effective student grapevine operated in their undergraduate program. The grapevine was used to disseminate information about all aspects of the course. Other strategies discussed by the participants were 'playing the game' and doing only what was necessary to complete the undergraduate program. This paper describes the learning strategies used by nursing students during their clinical practice, which has implications for clinical teachers and schools of nursing. PMID- 11785871 TI - Vaccination of turkeys with an avian pneumovirus isolate from the United States. AB - Four-week-old poults obtained from avian pneumovirus (APV) antibody-free parents were vaccinated with different serial 10-fold dilutions of cell culture propagated APV vaccine. The birds were vaccinated with 50 microl into each conjunctival space and nostril (total of 200 microl). Each poult of each group was vaccinated in groups that received doses of 4 x 10(4), 4 x 10(3), 4 x 10(2), 4 x 10(1), or 4 x 10(0) 50% tissue culture infective dose (TCID50) of APV vaccine, respectively. Respiratory signs were seen between 3 and 12 days postvaccination (PV) in the poults that were vaccinated with 4 x 10(4), 4 x 10(3), and 4 x 10(2) TCID50, respectively. In these groups, APV was detected from swabs collected at 5 days PV and seroconversion was detected at 2 wk PV. The groups that were originally vaccinated with 4 x 10(1) and 4 x 10(0) TCID50 developed mild clinical signs after vaccination, but neither virus nor antibody was detected PV. At 2 wk PV (6 wk of age), birds from each group, along with five unvaccinated controls, were challenged with APV. Upon challenge, the 4 x 10(4) and 4 x 10(3) TCID50 groups were protected against development of clinical signs and were resistant to reinfection. The group previously vaccinated with 4 x 10(2) TCID50 developed clinical signs after challenge that were considerably milder than those seen in the groups that had previously been vaccinated with lower doses or no virus. Even though 4 x 10(2) TCID50 vaccine dose administered by intranasal ocular route resulted in infection, incomplete protection resulted with this pivotal dose. Upon challenge, the 4 x 10(1) and 4 x 10(0) TCID50 groups exhibited milder disease signs than those seen in the challenged unvaccinated controls. In these groups, APV was detected in preparations of swabs collected at 5 days postchallenge (PC) and seroconversion was detected at 2 wk PC. These results indicate that the dose of APV vaccine that causes protection is higher than that required to produce infection. PMID- 11785872 TI - Aerosol transmission of arthropathic and amyloidogenic Enterococcus faecalis. AB - One-day-old brown layer chicks were exposed to an aerosol of an arthropathic and amyloidogenic Enterococcus faecalis strain alone or after being subjected to treatment with formaldehyde gas (100-200 ppm). Four-day-old chicks were also treated with the same aerosol but after treatment with a Newcastle disease vaccine virus (NDVV) aerosol or intramuscular injection with methylprednisolon at day 1. The same E. faecalis strain was inoculated intramuscularly in day-old chicks as positive control. Bacteremia with time showed that 24 hr after the aerosol the day-old exposed chicks had the highest rate of positive blood cultures (70%-80%). Lower numbers of bacteremic birds at this point in time were found in the chicks treated with E. faecalis aerosol at day 4 (3/10 in the methylprednisolon-treated group and 0/10 in the NDVV-treated group) and the E. faecalis intramuscular-injected group at day 1 (2/10). Formaldehyde gas treatment did not favor the occurrence of bacteremia. NDVV aerosol exposure or injection with corticosteroids did not favor the occurrence of bacteremia 24 hr after E. faecalis aerosol exposure at day 4 either, although 66 days after aerosol, one bird (1/14) treated with NDVV showed bacteremia. A few bacteremic birds were found 10 days after aerosol in the NDVV- and methylprednisolon-treated groups, whereas at 14 days after aerosol, one bacteremic bird was seen in the group subjected to E. faecalis aerosol at day 1, indicating the occurrence of chronic bacteremia. In contrast to the E. faecalis intramuscular-inoculated birds, no joint pathology was seen in the aerosol-exposed groups in spite of the occurrence of chronic bacteremia. PMID- 11785873 TI - The spread of Salmonella gallinarum 9R vaccine strain under field conditions. AB - A live vaccine based on an attenuated Salmonella gallinarum 9R strain is in use in a Salmonella enteritidis control program in commercial layer flocks in The Netherlands. In a field study, the potential spread of the vaccine strain from vaccinated flocks to nonvaccinated flocks has been studied after both the primary and the booster injection at four different rearing farms and at one layer farm. The vaccinated and the nonvaccinated flocks were monitored at regular intervals by bacteriologic and serologic examination. In this field study, no evidence was found for the fecal spread of the vaccine strain. PMID- 11785874 TI - Enhanced recovery of avian influenza virus isolates by a combination of chicken embryo inoculation methods. AB - Since 1993, 14 cases of avian influenza from four different states in the U.S.A. have been diagnosed by virus isolation from eight avian species. Only 11 of the 14 avian influenza virus (AIV) primary isolations would have been successful if only the standard protocol for AIV isolation, i.e., inoculation of specific pathogen-free embryonating chicken eggs (ECEs) by the chorioallantoic sac (CAS) route, had been followed. Primary isolation attempts were negative for AIV in three cases in which ECEs were inoculated by the CAS route; AIV could not be detected by hemagglutinating activity, agar gel immunodiffusion test or negative stain electron microscopy. However, in these three cases, primary isolations of AIV were achieved by inoculation of ECEs into either the yolk sac or onto the chorioallantoic membrane. PMID- 11785875 TI - Efficacy and safety of an infectious bursal disease virus intermediate vaccine in ovo. AB - The study was divided into two experiments. In the first experiment, the efficacy of in ovo intermediate vaccine against infectious bursal disease virus (IBDV) was determined by challenge at 21 days of age with virulent IBDV in specific-pathogen free (SPF) and commercial chickens. This vaccine was able to induce active immunity and to protect SPF chickens to challenge; protection was not complete in commercial chickens, as testified by bursal lesions, bursal index after challenge, and vaccine immunoresponse. In order to detect field and vaccinal viruses, immunoperoxidase staining, enzyme-linked immunosorbent assay, capture, and reverse transcriptase-polymerase chain reaction (RT-PCR) were tested; the RT PCR was more effective at detecting both kind of viruses. In the second experiment, the immunosuppressive effect of in ovo vaccination was determined by evaluating the immunoresponse against Newcastle disease virus (NDV) vaccination effected at 10 days in both SPF and commercial chickens vaccinated in ovo. The in ovo vaccine causes a reduction of NDV immunoresponse, as testified by lowest geometric mean titer in group I (SPF chickens vaccinated against IBDV in ovo and against NDV at 11 days). In commercial chickens, immunoresponse to NDV vaccination was not influenced by in ovo vaccination. PMID- 11785876 TI - Dynamics of Salmonella contamination in a commercial quail operation. AB - Control of carcass contamination requires knowledge of the source and dynamics of spread of Salmonella in commercial poultry production. We examined Salmonella contamination at a U.S. commercial quail operation. Pulsed-field gel electrophoresis (PFGE) was used to type isolates in order to trace Salmonella throughout this production environment. During a 6-mo survey, Salmonella serotypes hadar, typhimurium, typhimurium variant Copenhagen, and paratyphi were encountered within this poultry operation. Ninety-four percent of the Salmonella isolated from breeder and production houses and from carcass rinses belonged to Salmonella serotypes typhimurium variant Copenhagen and hadar. There were six distinct S. typhimurium variant Copenhagen genetic types, as identified by PFGE, present within this particular poultry operation. Seventy-nine percent of S. typhimurium variant Copenhagen identified from the environment of the breeder and production houses produced the same PFGE pattern. Thirty-eight percent of S. typhimurium Copenhagen isolated from carcass rinses and the breeder house shared the same PFGE DNA pattern. This study demonstrates the transmission of salmonellae throughout this production environment, from the breeders to their progeny and to the birds ultimately processed for human consumption. PMID- 11785877 TI - Prevalence of Clostridium perfringens in commercial broiler hatcheries. AB - Clostridium perfringens, a cause of human foodborne and poultry disease, has been isolated from the intestinal tract of poultry and from the processed carcass. Little is known about the incidence and sources of this pathogen in the poultry production environment. To determine if the broiler hatchery is a possible source of C. perfringens, we collected samples from three hatcheries, each operated by a different poultry integrator, and the presence of C. perfringens in these samples was determined. For each sampling period, eggshell fragments, chick fluff from the hatcher, and paper pads stored in the hatchery before use with chicks and after placement beneath chicks for 1 hr were evaluated. Clostridium perfringens was found in eggshell fragments, fluff, and paper pads in each of the three hatcheries. The percentages of C. perfringens-positive samples from the three hatcheries ranged from 13% to 23%, with an overall incidence of 20%. Positive samples were consistently found, i.e., detected on each of the nine sampling days (three sampling days for each of three hatcheries). These results suggest that the hatchery is a potential source/reservoir for C. perfringens in the integrated poultry operation. PMID- 11785878 TI - Isolation and characterization of a novel antigenic subtype of infectious bronchitis virus serotype DE072. AB - Three infectious bronchitis virus (IBV) isolates, CU82792, CU82805, and CU82808, were recovered from sentinel chickens placed with three different layer flocks of a large commercial poultry farm in New York State. The three isolates were classified as members of the DE072 serotype on the basis of 1) their S1 genes could be amplified with only a modified primer designed for the DE072 serotype and 2) their restriction fragment length polymorphism patterns, after digestion with endonucleases HaeIII, BstyI and XcmI, were indistinguishable from that of DE072 virus. Additional characterization of one of the isolates, CU82805, revealed that its S1 gene bears approximately 96% identity at the nucleotide level and 94% identity at the amino acid level with DE072. Yet, in an in vitro reciprocal virus neutralization test, only a one-way neutralization was observed, i.e., antiserum to CU82805 neutralized DE072, whereas CU82805 was not neutralized by DE072 antiserum. Implications of these findings with regard to IBV diagnosis and immunization are discussed. PMID- 11785879 TI - Novel infectious bronchitis virus S1 genotypes in Mexico 1998-1999. AB - Seventeen infectious bronchitis virus (IBV) field isolates recovered from commercial broiler flocks in Mexico were identified by reverse transcription polymerase chain reaction cycle sequencing of the S1 gene. The isolates were obtained from broilers on farms from the neighboring states of Queretaro and San Luis Potosi in 1998 and 1999. Flocks had an ongoing history of bacterial complicated respiratory disease with mortality rates as high as 28% in spite of receiving live vaccinations for Massachusetts and Connecticut strains of IBV. Sequence analysis of the S1 gene identified two unique genotypes that have been described, as of this time, only in Mexico and thus appear to represent strains indigenous to the country. The Mex/1765/99 genotype was isolated from 64% (11/17) of the respiratory disease outbreaks. Three isolates (18%) were similar to the BL 56 genotype, a unique Mexican IBV strain observed initially in 1996. In addition to the two indigenous strains, three isolates (18%) were found to be the Connecticut genotype. PMID- 11785880 TI - Seroprevalence of Ornithobacterium rhinotracheale infection in commercial laying hens in the north central region of the United States. AB - This study was the first to examine the seroprevalence of Ornithobacterium rhinotracheale (ORT) within a commercial egg layer population. Serum samples collected from egg production companies were examined by serum plate agglutination test (SPAT) and outer membrane protein-based enzyme-linked immunosorbent assay (ELISA). Results show that 90% of layer flocks were positive by SPAT and 100% by ELISA. Of the pullet flocks examined, 43% and 52% were positive by SPAT and ELISA, respectively. Our study indicates that the prevalence of ORT antibody is high in the commercial layer population, suggesting that this respiratory pathogen can easily spread through multiple-age layer farms from older flocks to newly housed pullet flocks. PMID- 11785881 TI - Staphylococcus aureus pneumonia in turkey poults with gross lesions resembling aspergillosis. AB - The present report describes a case of Staphylococcus (Staph.) aureus pneumonia in turkey poults. Initially, 3-day-old poults with a history of increased mortality were submitted for necropsy. The poults had severe bilateral consolidation of the lungs with miliary caseous nodules. The gross lesions in the lungs were highly suggestive of aspergillosis. The next day, postmortem examinations were performed on 60 dead poults at the farm, and all 60 had similar lung lesions. Histopathologic examination of affected lungs revealed severe subacute multifocal bronchopneumonia with intralesional bacteria. Tissue Gram stain of lung sections demonstrated gram-positive bacterial cocci. Gomori methenamine silver stain of the lungs failed to demonstrate fungal agents. The histologic distribution of the lesions suggested an aerogenous route of infection. Staphylococcus aureus was isolated in pure culture from affected lungs. Hatchery contamination was suspected because of the severity and early onset of the lesions. Bacterial monitoring at the hatchery demonstrated marked Staph. aureus contamination in two setters, a hatcher's air duct, and the poult room. Improved hatchery cleaning and disinfection prevented a reoccurrence of the problem. PMID- 11785882 TI - Genomic identification and characterization of avian adenoviruses associated with inclusion body hepatitis. AB - Four pathogenic avian adenovirus isolates associated with inclusion body hepatitis and mortality in commercial broiler chicks and chickens were characterized and identified. These group I avian adenovirus isolates were classified as group E (serotypes 6, 7, 8, and 9) avian adenoviruses on the basis of the restriction enzyme patterns of their viral DNA. Isolate 3718 was neutralized by a serotype 6 reference avian adenovirus antiserum and isolates 8193, 8380, and 8565 were all neutralized by a serotype 8 reference avian adenovirus antiserum by virus neutralization assays. Infectivity and virulence such as mortality, hemorrhages, enlarged green livers with intranuclear inclusion bodies, stunting, intestinal sloughing, and poor feathering were observed in specific-pathogen-free chicken embryos and were identical for all four isolates when embryos were inoculated via the yolk sac and/or chorioallantoic membrane. Complete mortality was observed within 72 hr postinoculation in specific-pathogen free (SPF) chickens inoculated intramuscularly for all four avian adenovirus isolates. PMID- 11785883 TI - Chicken infectious anemia in Mexico: virus identification and serology survey. AB - Three chicken infectious anemia (CIA) virus strains were isolated from 10 different sick broiler and replacement chicken flocks with the MDCC-MSB1 cell line. One-day-old specific-pathogen-free chicks were inoculated later, with the three original samples being positive in tissue culture; one induced signs and lesions, another only lesions typical for CIA. One isolate was selected for further trials and showed resistance to chloroform and heat (75 C for 5 min) and passed through a 45-nm filter membrane but did not pass through the 22-nm filter. These characteristics were similar to the Del Rose reference strain of chicken anemia virus. By electron microscopy, the diameter of particles obtained from the pellet of infected cell cultures was between 22 and 27 nm. Serology survey carried out with 580 serum samples from different poultry farms all over the country with a commercial enzyme-linked immunosorbent assay kit gave proof of widespread seroconversion, indicating that CIA should be considered endemic to Mexico. PMID- 11785884 TI - Induction of humoral immune response and protective immunity in chickens against Salmonella enteritidis after a single dose of killed bacterium-loaded microspheres. AB - Formalin-inactivated Salmonella enteritidis phage type 4 strain 119/95 (SE) was encapsulated in biodegradable poly (DL-lactide co-glycolic acid) PLGA; (65:35) microspheres by a modified water-in-oil-in-water (w/o/w) double-emulsion solvent extraction/evaporation technique. These SE-loaded microspheres (SE-MS) were porous and spherical in shape with diameters of 0.4-10 microm and 20-80 microm in two preparations. SE-MS were subsequently used to vaccinate specific-pathogen free chickens in a single dose in order to investigate the potency of a single dose vaccination in inducing immune responses and protective immunity. In Experiment 1, 4-wk-old chickens that were vaccinated intramuscularly with 20-80 microm SE-MS generated long lasting (over 6 mo) and persistently high serum anti SE immunoglobulin (Ig)G antibody response. In Experiment 2, 2-wk-old chickens were vaccinated orally with 0.4-10-microm or intramuscularly with 20-80-microm SE MS and challenged with 10(9) colony-forming units of homologous SE strain at 6 wk postvaccination. When challenged intramuscularly, one each of the orally vaccinated (n = 10) and the intramuscularly vaccinated birds (n = 10) showed clinical signs and death, whereas all of the nonvaccinated control birds (n = 12) were sick and 11 of them were killed. When challenge was via oral route, 26.1% of cloacal swabs and 24.0% of organs (liver, spleen, and cecum) collected from orally vaccinated birds (n = 35) were positive for SE, comparable to 27.9% of feces and 18.7% of organs from the intramuscularly vaccinated birds (n = 35). These figures were significantly lower than those for nonvaccinated birds (n = 30) from which 59.3% of feces and 44.0% of organs tested SE positive (P < 0.05). The humoral immune response was also determined after vaccination with a single dose. The intramuscular vaccination elicited higher serum IgG response than oral administration, but the latter elicited a significant intestinal mucosal IgA antibody response. This is the first evidence that chickens vaccinated with killed SE-loaded PLGA microspheres, intramuscularly and orally in a single dose, developed systematic and local immune responses, thereby conferring protective immunity. PMID- 11785885 TI - DNA fingerprint patterns of Pasteurella multocida from the same turkey farm on the same and different years. AB - The DNA fingerprint profiles of 126 isolants of Pasteurella multocida from 41 turkey farms in Missouri were analyzed after digestion with the restriction endonuclease HhaI and compared with their somatic antigenic type. The goal was to determine if the same isolant of P. multocida was reisolated from the the same farm during the same and consecutive years and after an interval of one or more years. Of the 37 pairs of P. multocida collected during the same year from the same turkey farms, the DNA fingerprint profiles were the same with 26 pairs (70.3%) and different with 11 pairs (29.7%). Of the 33 pairs of P. multocida collected during consecutive years from the same 22 turkey farms, 21 pairs (63.6%) were the same and 12 pairs (36.4%) were different. Of the 15 pairs of P. multocida collected with an interval of one or more years between them from the same 14 turkey farms, only four pairs (26.7%) were the same and 11 pairs (73.3%) were different. There did not appear to be any relationship between the DNA fingerprint profiles and the typing of their somatic antigens because, although 44 pairs of isolants had the same DNA fingerprint profile and somatic antigenic type, 42 pairs differed in these parameters when all pairs were combined. PMID- 11785886 TI - Proliferation of lung macrophages in acute fatal viral infections in chickens. AB - Marked proliferation of macrophages engulfing yellow pigments and fragmented erythrocytes were seen in the air capillaries and blood capillaries of the lungs of chickens affected with acute fatal viral hydropericardium syndrome, highly pathogenic infectious bursal disease, and highly pathogenic avian influenza. Proliferation of lung macrophages was associated with systemic proliferation of macrophages. Acute destruction of erythrocytes in these infections may have induced systemic hyperplasia of macrophages. The acute and severe proliferation of lung macrophages may cause acute respiratory dysfunction and be one of the factors inducing mortality in infected chickens. This syndrome may be categorized as "virus-associated hemophagocytic syndrome." PMID- 11785887 TI - Pathogenicity of serotype 1 fowl adenovirus in commercial broiler chickens. AB - The pathogenicity of a serotype 1 fowl adenovirus (FAV-99ZH), isolated from broiler chickens exhibiting gizzard erosion, was investigated in commercial broiler chickens. Five-, 3-, and 1-wk-old commercial broiler chickens were inoculated with FAV-99ZH by both oral and ocular routes. In the 5-wk-old chickens (trial 1), none of which had the maternal antibody to FAV-99ZH, severe gizzard erosions were observed on days 5, 7, and 10 postinoculation (PI). Among the 3-wk old chickens (trial 2), which were separated into a control group and three treatment groups according to their maternal antibody titer levels, some chickens showed clinical signs such as depression and anorexia. Compared with the control group, all the treatment groups showed decreased weight gain. One treatment group, moreover, showed significantly decreased (P < 0.05) weight gain on day 10 PI. Severe gizzard lesions, such as erosion or ulcers, were observed from day 4 PI in all treatment groups regardless of their maternal antibody levels. The 1-wk old chickens (trial 3) were separated into a control group and two treatment groups according to their titer levels of the inoculated virus. In spite of high maternal antibody levels, severe gizzard lesions were observed in both treatment groups, which also showed decreased weight gain. One treatment group, inoculated with the higher dose, showed significantly decreased (P < 0.05) weight gain on days 10 and 14 PI compared with the control group. Fowl adenovirus was recovered mainly from gizzard and rectal (including feces) samples from inoculated chickens but was not recovered from liver samples in any of the trials or in any of the control chickens. Although the reproduced disease was similar to that described in a previous report of experimental infection of specific-pathogen-free (SPF) white leghorn chickens with fowl adenovirus, the pathogenicity of FAV-99ZH in commercial broiler chickens was more severe than that in the SPF white leghorn chickens. The results of the present study indicate that FAV-99ZH isolated from gizzard erosion had pathogenicity and produced severe lesions in the gizzards of broiler chickens and that FAV-99ZH could infect and produce illness in broiler chickens with maternal antibodies against this virus. PMID- 11785888 TI - Viral and bacterial agents associated with experimental transmission of infectious proventriculitis of broiler chickens. AB - Proventriculitis of broilers can be reproduced by oral inoculation of day-old chicks with a proventricular homogenate from affected 3-wk-old broilers. The objective of the following studies was to isolate from this homogenate viral and bacterial isolates that could produce proventriculitis. A monoclonal antibody to infectious bursal disease virus (IBDV) was used to precipitate virus from the homogenate. A primary chicken digestive tract cell culture system was also used to isolate virus from a 0.2-microm filtrate of the homogenate, and a bacterium was also isolated from the homogenate. In trial 1, day-old birds were orally inoculated with either proventriculus homogenate or monoclonal antibody immunoprecipitated IBDV (MAB-IBDV). At 4, 7, 14, and 21 days postinfection (PI), 12 birds from each treatment group were subjected to necropsy. In trial 2, day old birds were orally inoculated with either infectious proventriculus homogenate, suspect virus isolated in cell culture and propagated in embryo livers and spleens, or a bacterial isolate. Twelve birds from each treatment were subjected to necropsy at days 7, 14, 21, and 28 PI. In trial 3, treatments were maintained in negative pressure isolation chambers, and an additional treatment included virus plus bacterial isolate. Twenty-four birds from each treatment were subjected to necropsy at day 21 PI. In trial 1, infectious homogenate decreased body weight and relative gizzard weights at 4, 7, 14, and 21 days PI. Proventriculus relative weight was increased at days 7, 14, and 21 PI, and proventriculus lesion scores were increased at days 14 and 21 PI. Bursa/spleen weight ratios were decreased at day 14, and feed conversion was increased at days 4 and 21. The MAB-IBDV treatment decreased proventriculus and gizzard relative weights at day 4 PI, increased proventriculus lesion scores and bursa/spleen weight ratios at day 14, and decreased heterophil/lymphocyte ratios at day 21. In trial 2, all infected birds had significantly higher mean relative proventriculus weights at 21 days PI and had higher 4-wk mean proventriculus scores as compared with both control groups. In trial 3, birds treated with homogenate and birds treated with both suspect virus and the bacterial isolate had significantly higher proventriculus lesion scores; higher relative weights of proventriculus, gizzard, liver, and heart; lower body weights; and lower relative bursa weights compared with the saline control group. These studies suggest that infectious proventriculitis has a complex etiology involving both viral and bacterial infection. PMID- 11785889 TI - Pathogenicity of cell culture-derived and bursa-derived infectious bursal disease viruses in specific-pathogen-free chickens. AB - That passage of infectious bursal disease virus (IBDV) 30 and 40 times in an established cell line (BGM-70) resulted in loss of pathogenicity has been reported; however, both viruses maintained antigenicity and immunogenicity. That the passaged virus might have lost some ability to replicate in the natural host, resulting in lack of antigenic stimulation and a poor immune response, was speculated. In this study, the pathogenicity and the replication of the serorype 1 variant IN strain were investigated in specific-pathogen-free (SPF) chickens. The original bursa-derived virus was passaged 10 times (low passage [LP]) and 47 times (high passage [HP]) in BGM-70 cells. Two concentrations of the LP virus were used for inoculation of different groups of birds, high titer 1.5 x 10(5) 50% mean embryo infective dose (EID50) and low titer 1.5 x 10(2) EID50. Birds inoculated with the bursa-derived virus had significantly (P < 0.05) small bursas with severe inflammation and necrosis throughout the 21-day experimental period. Bursa and spleen/body weight ratios and bursal lesion scores of the birds inoculated with the LP and HP viruses were not significantly different from those of the uninoculated control group at any time postinoculation (PI). Virus replication in the bursa of Fabricius was investigated by virus isolation in SPF chicken embryos, immune electron microscopy (IEM), immunofluorescence (IF), and antigen-capture enzyme-linked immunosorbent assay (AC-ELISA). The virus was isolated from bursal tissues from birds inoculated with the bursa-derived virus from day 3 (first isolation attempt) through day 10 PI, and the highest virus concentration was detected at 3 days PI. Low virus titer was detected only at 3 days PI in chicken embryos inoculated with the bursal homogenates from birds inoculated with the LP virus at a high dose or the HP virus. No virus was isolated from birds inoculated with the LP virus at a low dose or the uninoculated control group. The virus antigen was also detected in bursal tissues collected from birds inoculated with the bursa-derived virus at 3, 5, and 7 days PI by IEM and AC-ELISA and until day 10 PI by IF. No virus antigen was detected in bursal tissues collected from birds inoculated with the cell culture-adapted viruses by embryo inoculation, IEM, IF, or AC-ELISA. The virus or its RNA was detected in the bursal homogenates up to 21 days PI by reverse transcriptase/polymerase chain reaction. These results indicated that adaptation of IBDV to BGM-70 cell culture resulted in a significant reduction in the ability of the virus to replicate in the bursa of Fabricius, and, consequently, no lesions were detected. PMID- 11785890 TI - Induction of functional defects in macrophages by a poult enteritis and mortality syndrome-associated turkey astrovirus. AB - The interaction of a poult enteritis and mortality syndrome (PEMS)-turkey astrovirus-Ohio State University (TAst-OSU) with the mononuclear phagocytic system cells, namely macrophages, was examined after in vitro and in vivo exposure. In vitro exposures were performed by incubating adherent turkey macrophages with various volumes of 10(6) 50% embryo infective dose (EID50)/ml TAst-OSU stock, whereas for in vivo challenge, poults were given a 200 microl inoculum of 10(6) EID50/ml TAst-OSU stock at 7 days of age. Results show that TAst-OSU in vitro exposure reduced macrophage viability relative to controls (P < 0.05) and decreased phagocytosis (P < 0.05) and intracytoplasmic killing of Escherichia coli (P < 0.05) after a 42-48-hr exposure. Poults challenged with TAst-OSU in vivo recruited almost 50% fewer Sephadex-elicited inflammatory cells in the abdominal cavity (P < 0.05) as compared with the sham controls. Similar to in vitro exposure, macrophages isolated from in vivo TAst-OSU-challenged poults exhibited reduced percentage of phagocytic macrophages (P < 0.05) as well as fewer intracytoplasmic E. coli per phagocytic macrophage (P < 0.05). TAst-OSU challenged poults had a greater number of viable E. coli in their spleens (P < 0.05) after an intravenous E. coli challenge as compared with the non-TAst-OSU challenged control poults. Macrophage-mediated cytokines and metabolites were also examined during this study. Both in vitro and in vivo TAst-OSU challenge resulted in reduced interleukin (IL)-1 and IL-6 activity. On the contrary, nitrite levels in macrophage culture supernatant fraction of TAst-OSU-challenged macrophages were significantly higher (P < or = 0.05). The findings of these studies indicated that TAst-OSU challenge induced defects in macrophage effector functions, implying that PEMS-turkey astrovirus can potentially impair the immune response of turkeys, thereby leading to enhanced susceptibility of turkeys to secondary, perhaps even fatal, bacterial infections. PMID- 11785891 TI - Molecular characteristics of full-length genomic segment A of three infectious bursal disease viruses in China: two attenuated strains and one virulent field strain. AB - The full-length cDNA of genomic segment A of three infectious bursal disease viruses, two attenuated strains (HZ2 and JD1) and one virulent field strain (ZJ2000), was amplified in a single step by reverse transcription-polymerase chain reaction, cloned into pGEM-T Easy Vector, and sequenced. The full length of cloned segment A contains 3259 nucleotides, which includes two partially overlapping open reading fragments (ORFs) ORF1 and ORF2, flanked by 5' and 3' noncoding regions. These strains shared high sequence identity with each other either at the nucleotide or deduced amino acid level. Strains HZ2 and JD1 were highly related to two attenuated strains, CEF94 and P2, whereas ZJ2000 was closely related to two other virulent strains, Cu-1 and Harbin. Substitutions of four amino acids at positions 253, 279, 284, and 330, a common feature of attenuated and most virulent strains, were also observed in these three strains. Two major hydrophilic peaks were conserved in the three strains; however, there are two amino acid substitutions at positions 280 (N to S) and 290 (M to L) in the second minor hydrophilic peak for all three strains, which might have a critical influence on antigenicity. Two amino acid substitutions near the VP2-VP4 cleavage site were identified in virulent strain JZ2000, which might be involved in increasing the virulence of the virus. Phylogenetic analyses indicated that these three Chinese strains are most closely related to some European virulent strains but are distinct from very virulent infectious bursal disease virus and variant strains. PMID- 11785892 TI - Determination of close genetic relatedness of the major Salmonella enteritidis phage types by pulsed-field gel electrophoresis and DNA sequence analysis of several Salmonella virulence genes. AB - Salmonella enteritidis (SE) is an important cause of egg-associated outbreaks in both Europe and the United States. Phage typing has become an important epidemiologic tool in identifying the source of outbreaks. Limitations of phage typing have become apparent with wholesale egg distributors that have multiple suppliers in an area where a particular phage type is endemic. Several different molecular typing methods were evaluated for their discriminatory power to identify genetic differences among different SE phage types isolated in Europe and the United States. Pulsed-field gel electrophoresis (PFGE) identified a single DNA pattern among the different SE phage types. Comparison of the nucleotide sequence for several Salmonella virulence genes failed to identify a single nucleotide change in the gene sequences from most SE isolates, regardless of phage type. On the basis of these results, the different SE phage types appear to be genetically related or clonal. However, with primers 1283 and Opa4, it was possible to differentiate not only SE isolates from different geographic locations but those within a specific geographic locale as well by random amplified polymorphic DNA polymerase chain reaction. Any chance for discerning genetic differences among isolates will need to rely on molecular techniques other than PFGE. PMID- 11785893 TI - Incidence of Clostridium perfringens in broiler chickens and their environment during production and processing. AB - During a calendar year, a study was conducted involving 16 broiler flocks on four different farms, two farms belonging to each of two major U.S. poultry integrators. As determined by the detection of Clostridium perfringens in fecal or cecal samples, 15 (94%) of the flocks became positive for this bacterial enteropathogen, and only one remained negative throughout the 6-to-8-wk rearing period. Paper pads beneath chicks that were transported from the hatchery to the rearing house were contaminated with C. perfringens in 15 (94%) of the flocks. When sampled biweekly through grow out, 13 of the flocks were C. perfringens positive at 2 wk of age. These results suggest that colonization of the intestinal tract of broilers by C. perfringens is an early event. Of the environmental samples, all but feed in the hopper were contaminated before placement for at least one of the rearing periods. All sample types were contaminated at some point during the 6-to-8-wk grow-out period. Of the on-farm environmental samples, the highest incidences (percentage positive) of C. perfringens were detected in wall swabs (53%), fan swabs (46%), fly strips (43%), dirt outside the house entrance (43%), and swabs of workers' boots (29%). Birds were usually transported to the processing plant in coops that were already contaminated with C. perfringens. In the plant, C. perfringens was isolated more frequently from samples of scald water than from those of chill water. Clostridium perfringens was recovered from broiler carcasses after chilling in 13 (81%) of the 16 flocks. The proportion of C. perfringens-positive carcasses for the contaminated flocks ranged from 8% to 68% with a mean of 30%. PMID- 11785894 TI - Detection of infectious bursal disease vaccine viruses in lymphoid tissues after in ovo vaccination of specific-pathogen-free embryos. AB - Control of infectious bursal disease virus (IBDV) by vaccination is important for poultry production worldwide. Two vaccines, an IBDV immune complex (ICX) vaccine and an IBDV-2512 vaccine, were administered at 100 mean embryo infectious dose to specific-pathogen-free 18-day-old broiler embryos in ovo. At 3, 6, 9, 15, and 21 days post in ovo vaccination (PIOV), bursa, spleen, and thymus tissues were collected and analyzed for virus protein by antigen capture chemiluminescent enzyme-linked immunosorbent assay (ELISA). Chicks were bled and antibody titers were determined by the antibody ELISA. At 21 days PIOV, chickens were challenged with a 1:500 dilution of an antigenic standard IBDV strain. At 28 days PIOV, birds were euthanatized and bursa weight:body weight ratios were determined. Embryos vaccinated with either vaccine exhibited 92% hatchability; however, within 1 wk of hatch, birds vaccinated with IBDV-2512 showed 56% mortality, whereas those given IBDV-ICX had only 3.2% mortality. Both IBDV-ICX and IBDV-2512 vaccines were detected in bursa, spleen, and thymus at day 3 PIOV. A 5-day delay in virus replication was observed with IBDV-ICX vaccine. By day 15 PIOV, the IBDV ICX was no longer detectable in the bursa and spleen but persisted in the thymus. The IBDV-2512 vaccine persisted in the spleen and thymus on day 15 PIOV. By day 21 PIOV, neither vaccine virus was detected in any lymphoid organ. This assay can be useful in the early detection of vaccine virus in the tissues of chickens vaccinated via the in ovo route. Both vaccines caused bursal atrophy at all times PIOV. The IBDV-2512 caused splenomegaly at day 6 PIOV, whereas splenomegaly was not seen in IBDV-ICX-vaccinated birds until day 9 PIOV. Thymus atrophy was observed in IBDV-2512-vaccinated chicks from day 3 PIOV, whereas this occurred on day 15 PIOV in IBDV-ICX-vaccinated birds. Bursa weight: body weight ratios in IBDV-ICX-vaccinated unchallenged and vaccinated challenged birds were not different (P < 0.05). PMID- 11785895 TI - Virulence of pigeon-origin Newcastle disease virus isolates for domestic chickens. AB - The virulence of six pigeon-origin isolates of Newcastle disease virus (NDV) was evaluated before and after passage in white leghorn chickens. Four isolates were defined as pigeon paramyxovirus-1 (PPMV-1) and two isolates were classified as avian paramyxovirus-1 (APMV-1) with NDV monoclonal antibodies. The four PPMV-1 isolates were passaged four times in chickens, and the APMV-1 isolates were passaged only once. Infected birds were monitored clinically and euthanatized. Tissues were collected for histopathology, in situ hybridization with a NDV matrix gene digoxigenin-labeled riboprobe, and immunohistochemistry with an anti peptide antibody to the nucleoprotein. Mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index tests performed before and after passage in chickens demonstrated increased virulence of the passaged PPMV-1 isolates and high virulence of the original isolates of APMV-1. Sequence analysis of the fusion protein cleavage site of all six isolates demonstrated a sequence typical of the virulent pathotype. Although the pathotyping results indicated a virulence increase of all passaged PPMV-1 isolates, clinical disease was limited to depression and some nervous signs in only some of the 4-wk-old specific-pathogen-free white leghorns inoculated intraconjunctivally. However, an increased frequency of clinical signs and some mortality occurred in 2 wk olds inoculated intraconjunctivally with passaged virus. Histologically, prominent lesions in heart and brain were observed in birds among all four groups inoculated with the PPMV-1 isolates. The behavior of the two pigeon-origin APMV-1 isolates when inoculated into chickens was characteristic of velogenic viscerotropic NDVs and included necro-hemorrhagic lesions in the gastrointestinal tract. PMID- 11785896 TI - Pathogenicity of different serogroups of avian salmonellae in specific-pathogen free chickens. AB - The pathogenicity of one isolate of Salmonella typhimurium, four isolates of Salmonella heidelberg, three isolates of Salmonella kentucky, two isolates of Salmonella montevideo, one isolate of Salmonella hadar, and two isolates of Salmonella enteritidis (SE), one belonging to phage type (PT)13a and the other to PT34, was investigated in specific-pathogen-free chicks. Three hundred eighty four chicks were separated into 16 equal groups of 24 chicks. Thirteen groups were inoculated individually with 0.5 ml of broth culture containing 1 x 10(7) colony-forming units (CFU) of either S. typhimurium (one source), S. heidelberg (four sources), S. montevideo (two sources), S. hadar (one source), S. kentucky (three sources), SE PT 13a (one source) or SE PT 34 (one source) by crop gavage. Two groups of 24 chicks were inoculated in the same way with 1 x 10(7) CFU of SE PT4 (chicken-CA) and Salmonella pullorum. Another group of 24 chicks was kept as an uninoculated control group. The chicks were observed daily for clinical signs and mortality. Isolation of salmonella was done from different organs at 7 and 28 days postinoculation (DPI). All the chicks were weighed individually at 7, 14, 21, and 28 DPI. Two chicks chosen at random from each group were euthanatized and necropsied at 7 and 14 DPI and all the remaining live chickens, at 28 DPI. Selected tissues were taken for histopathology at 7 and 14 DPI. Dead chicks were examined for gross lesions and tissues were collected for histopathology. Chicks inoculated with S. pullorum had the highest mortality (66.66%), followed by S. typhimurium (33.33%). Chicks inoculated with S. heidelberg (00-1105-2) and SE PT4 (chicken-CA) had 12.5% mortality and 8.3% mortality, respectively, with SE PT 13a. Ceca were 100% positive for salmonellae at acute or chronic infection compared with other organs. Mean body weight reduction ranged from 0.67% (inoculated with S. kentucky 00-926-2) to 33.23% (inoculated with S. typhimurium 00-372) in the inoculated groups at different weeks compared with uninoculated controls. Gross and microscopic lesions included peritonitis, perihepatitis, yolk sac infection, typhilitis, pneumonia, and enteritis in some groups, especially those inoculated with S. typhimurium, S. heidelberg (00-1 105-2), SE PT4 (chicken CA), and S. pullorum. PMID- 11785897 TI - Development and characterization of monoclonal antibodies to subgroup J avian leukosis virus. AB - In an attempt to develop a specific diagnostic test for avian leukosis virus (ALV) subgroup J (ALV-J) strain Hc1, four monoclonal antibodies (MAbs), JE9, G2, 145, and J47, were generated that are specific for ALV-J envelope glycoprotein, gp85. Polymerase chain reaction (PCR) was used to amplify genomic pro-viral DNA of Avian Disease and Oncology Laboratory (ADOL)-Hc1 and ADOL-4817 envelope genes. Both open reading frames encoding glycoproteins gp85 and gp37 were cloned into baculoviruses. Abundant expression of gp85 and gp37 was detected in the recombinant viruses with specific antibody to Hc1 strain of the ALV-J. The expressed proteins were used for immunization of mice to produce hybridoma cell lines secreting MAbs specific to ALV-J envelope protein. A panel of MAbs was generated by fusing NS1 myeloma cells and spleen cells from mice immunized with the recombinant baculoviruses. With the use of an immunofluorescence assay, three MAbs (JE9, G2, 145) reacted with ALV-J but not with subgroups A, B, C, D, or E of ALV. MAb J47 reacted with all exogenous subgroups of ALV including A, B, C, D, and J but not with endogenous subgroup E viruses. Western blot analysis was performed with all four MAbs against recombinant baculovirus and Hc1-infected chicken embryo fibroblast (CEF) lysates. A major band with a molecular weight about 90 kD corresponding to the size of ALV-J envelope was consistently obtained. With these MAbs, we detected the Hc1 antigen in CEFs infected with several ALV-J viruses isolated in the United States and also in tissue sections from chickens infected with Hc1 strain of ALV-J. These MAbs will be useful reagents for the diagnosis of ALV-J infection because they recognize a common antigenic epitope in six isolates tested thus far. PMID- 11785898 TI - Ultrastructural location of the cross-protection factor on in vivo and in vitro grown Pasteurella multocida. AB - Pasteurella multocida from infected turkey tissues expresses a unique immunogen called cross-protection factor (CPF) that induces immunity to challenge by both homologous and heterologous serotypes. In this study, we used a monoclonal antibody (AMP MAb) to CPF and protein A-colloidal gold (PACG) to locate CPF on P. multocida. After incubation with AMP MAb and PACG, CPF was detected at the bacterial surface and cell periphery of P. multocida in infected turkey liver and P. multocida isolated from infected turkey blood. CPF was not detected on P. multocida incubated with control monoclonal antibody. Pasteurella multocida isolated from infected turkey blood and cultivated in the peptone-based medium did not express CPF consistently, and some cells contained more CPF than others. The location of CPF also varied, and CPF was detected both intracellular and extracellular on the cell surface. In the latter cells, CPF was heavily concentrated to a specific lateral site or detected sloughing from the cell surface. These results correlate with laboratory observations that CPF detected on P. multocida from infected turkey tissues, P. multocida isolated from infected turkey blood, and P. multocida cultivated in peptone-based medium is associated with outer membrane fractions. PMID- 11785899 TI - Characterization of antibiotic-resistant bacteria in rendered animal products. AB - Antibiotics are used in food animal production to treat diseases and also to improve performance. Antibiotics are not used on all farms, and antibiotic resistance is occasionally found on farms that do not use antibiotics. Rendered animal protein products are often included in poultry feeds and could potentially serve as a source of antibiotic-resistant bacteria. One hundred sixty-five rendered animal protein products from cattle, poultry, and fish were aseptically collected from poultry feed mills. Fifty-five percent of the poultry meal samples had detectable levels of gram-negative bacteria ranging from 40 to 10,440 colony forming units/g of sample. Poultry meal and meat and bone meal had the greatest number of samples with bacteria resistant to five or more antibiotics. A high percentage of feed samples (85%) contained bacteria resistant to amoxicillin, ampicillin, clavulanic acid, or cephalothin, whereas few samples contained bacteria resistant to ciprofloxacin, kanamycin, or trimethoprim/sulfamethoxazole. Acinetobacter calcoaceticus, Citrobacter freundii, and Enterobacter cloacae were the most commonly isolated antibiotic-resistant bacteria. Isolation for Salmonella was also performed, with 14% of the meat and bone meal samples containing Salmonella sp. Only one of the meat and bone meal isolates, Salmonella livingstone, was resistant to five or more antibiotics. Many of the antibiotic resistant bacteria contained integrons, genetic elements that mediate multiple drug resistance. PMID- 11785900 TI - Differences in abilities to colonize reproductive organs and to contaminate eggs in intravaginally inoculated hens and in vitro adherences to vaginal explants between Salmonella enteritidis and other Salmonella serovars. AB - In Experiment 1, mature laying hens were inoculated intravaginally with 10(6) colony-forming units of Salmonella enterica serovar enteritidis (S. enteritidis), Salmonella typhimurium, Salmonella infantis, Salmonella hadar, Salmonella heidelberg, or Salmonella montevideo to compare their abilities to colonize the reproductive organs of chickens and to contaminate eggs. Salmonella enteritidis was more frequently recovered (from 11 of 40 eggs, 27.5%) than the other serovars, and especially the inner shell was contaminated with these organisms in 10 of 40 eggs (25.0%). The contamination rates and the viable counts in cloaca were significantly (P < 0.05) higher in hens inoculated with S. enteritidis than in those inoculated with the other serovars at 4 days postinoculation (PI). In the vagina, the positive rates were 90%-100% in hens inoculated with S. enteritidis, and the viable counts of the organisms in this portion were significantly (P < 0.05) higher than those of the other serovars at 2, 4, and 7 days PI. The ceca were colonized similarly by each serovar at 7 days PI. The spleen and ovary were infected with S. enteritidis in three and one hen, respectively. No Salmonella was recovered from liver and peripheral blood in any hen. Salmonella enteritidis was recovered from other oviductal portions than the vagina (10%-20%), whereas no forming egg was contaminated in the oviduct. In Experiment 2, the in vitro adherence of these six serovars to the vaginal epithelium was compared with vaginal explants. The mean number of S. enteritidis attaching to the secondary villi in the vaginal lumen was significantly (P < 0.05) higher than those of the other serovars. These results suggest that S. enteritidis has a specific advantage over the other Salmonella serovars by its capacity to colonize the vaginal tissues of hens, and this higher affinity of S. enteritidis to the vagina may play a significant role in the production of many S. enteritidis-contaminated eggs. PMID- 11785901 TI - Efficacy comparisons of disinfectants used by the commercial poultry industry. AB - Several commercially available disinfectants used by the poultry industry were evaluated for their effectiveness against selected bacteria and viruses. When tested in the absence of organic matter, most disinfectant products were effective at the manufacturer's recommended level within 10 min of contact time. However, when organic matter was present, longer contact times and/or higher disinfectant dosages were needed to maintain effectiveness. Pseudomona aeruginosa and infectious laryngotracheitis virus were very resistant organisms in the presence of organic matter. Evaluation of disinfectant efficacy against several microbials in the absence or presence of organic matter was highly practical, flexible, and reproducible. PMID- 11785902 TI - Antigenic and genomic relatedness of turkey-origin coronaviruses, bovine coronaviruses, and infectious bronchitis virus of chickens. AB - In earlier studies in our laboratory, we found that bovine coronavirus (BCV) was pathogenic for 1-day-old turkey poults. This finding prompted us to study the antigenic and genomic relatedness of turkey origin coronaviruses (TOCVs) to BCV. A one-step reverse transcription (RT)-polymerase chain reaction (PCR) targeting a 730-base pair fragment of the nucleocapsid (N) gene of BCV and a nested PCR targeting a 407-base pair fragment of the N gene were used in an attempt to detect TOCV from North Carolina, Indiana, and a prototype turkey coronavirus (TCV) obtained from the American Type Culture Collection. Both the one-step RT PCR and the nested PCR amplified cell culture-passaged isolates of calf diarrhea strains of BCV but none of the 15 tested TOCVs or transmissible gastroenteritis coronavirus of swine. TOCVs also did not cross-react in a BCV antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA) system with monoclonal antibodies (MAbs) against N, spike glycoprotein, and hemagglutinin esterase glycoprotein proteins of BCV as coating antibodies. The same TOCVs could be detected with primers designed from the genome of infectious bronchitis virus (IBV) of chickens. These primers amplified a 1082-base pair region spanning portions of the membrane glycoprotein (M) and N protein genes of IBV and TCV. The TOCVs also cross-reacted in an AC-ELISA with MAbs against the M and subunit 2 of spike glycoprotein of IBV. PMID- 11785903 TI - Mortality patterns associated with poult enteritis mortality syndrome (PEMS) and coronaviral enteritis in turkey flocks raised in PEMS-affected regions. AB - Poult enteritis mortality syndrome (PEMS) is an economically devastating disease. To date, many questions about the syndrome remain unanswered, including its cause, transmission of causative agent(s), and control methods. Turkey coronavirus (TCV) infection has been associated with some outbreaks of PEMS, with areas having a higher prevalence of TCV infection also experiencing an increased incidence of PEMS. This study was designed to establish mortality patterns for flocks experiencing excess mortality and TCV infection in PEMS-affected regions and to delineate the possible role of TCV in PEMS-affected flocks. Fifty-four commercial turkey flocks on farms in areas with and without a history of TCV infection were monitored for weekly mortality and for antibodies to TCV. Flocks were chosen on the basis of placement dates and were monitored from day of placement until processing. All flocks were tested for TCV by an indirect fluorescent antibody assay. PEMS status was determined with the use of the clinical definition of mortality greater than 2% during any 3-wk period from 2 wk of age through the end of brooding due to unknown cause. Of the 54 flocks, 24 remained healthy, 23 experienced PEMS, and 7 tested positive for TCV but did not experience PEMS. Ten flocks experienced PEMS and tested positive for TCV, whereas 13 flocks experienced PEMS and did not test positive for TCV. Four health status groups were evident: healthy, PEMS positive, TCV positive, and PEMS + TCV positive. Distinct mortality patterns were seen for each of the four health status groups. Whereas TCV was associated with PEMS in 43% of PEMS cases, 13 cases (57%) of PEMS did not involve TCV. Additionally, 7 out of 17 cases of TCV (41%) did not experience excess mortality (PEMS) at any time during brooding of the flock. The results of this study indicate that TCV can be associated with PEMS but is neither necessary nor sufficient to cause PEMS. PMID- 11785904 TI - Immunohistochemical localization of avian leukosis virus subgroup J in tissues from naturally infected chickens. AB - The tissue tropism of avian leukosis virus (ALV) subgroup J (ALV-J) was investigated in congenitally infected broiler chickens by an immunohistochemistry technique detecting gp85 viral glycoprotein. All organs examined contained detectable antigen. The most intense staining was in the adrenal gland, heart, kidney, and proventriculus. Intense staining for viral antigen in the heart may explain the ability of ALVs to cause cardiomyopathy. Although recent investigations failed to demonstrate specific viral staining in bone marrow from infected chickens, we were able to show moderate staining in myelocytic precursor cells in bone marrow. This finding agrees with previous work showing cell cultures of bone marrow are susceptible to ALV-J infection and the tendency of subgroup J to predominantly induce myeloid rather than lymphoid neoplasms. PMID- 11785905 TI - Phenotypic and molecular characterization of isolates of Ornithobacterium rhinotracheale from Peru. AB - Twenty-five isolates of Ornithobacterium rhinotracheale were examined by agar gel precipitation, immunoperoxidase assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blot analysis, and a polymerase chain reaction. All of the isolates were identified as serotype A. Protein profiles of whole cell extracts were similar for all the isolates, and a polypeptide with a molecular weight of 33 kD was a major component, being present in all the isolates. In the main, proteins of 33, 42, 52, and 66 kD were recognized in immunoblots with sera from chickens naturally exposed to O. rhinotracheale. A modified polymerase chain reaction assay identified O. rhinotracheale DNA from all the isolates and tracheal swabs, producing amplicons of 784 bp, and distinguished O. rhinotracheale from bacterial agents causing similar clinical signs. PMID- 11785906 TI - Effect of phenobarbital and spironolactone treatment on the oxidative metabolism of antipyrine by rat liver microsomes. AB - The effects of pretreating rats with the inducers, phenobarbital or spironolactone, on the formation rate of the three major oxidative metabolites of antipyrine in vitro by hepatic microsomal fractions have been investigated. Both inducers reduced the rate of 3-methylhydroxylation of antipyrine by approximately 50%. In contrast, N-demethylation and 4-hydroxylation were enhanced 1.7-fold and 3.4-fold, respectively, in case of phenobarbital induction and 1.4-fold and 2.6 fold, respectively, following spironolactone treatment. To elucidate the role of some cytochrome P450 isoenzymes in the production of the three major metabolites of antipyrine, the effects of form selective enzyme inhibitors on antipyrine oxidation were also studied. Troleandomycin did not alter 3-methylhydroxylation but reduced both N-demethylation and 4-hydroxylation of antipyrine in microsomes from induced rat liver. Cimetidine and chloramphenicol decreased the rate of formation of all three metabolites in microsomes from induced and uninduced animal livers as well. Chloramphenicol seemed to be the most potent inhibitor of in vitro antipyrine oxidation. Alpha-methyldopa significantly enhanced the rate of formation of 4-hydroxyantipyrine and slightly reduced the rate of N demethylation and 3-methylhydroxylation. According to the data obtained with microsomes from uninduced rat livers, the formation of the three major metabolites of antipyrine is extensively mediated by CYP2C11/C6. In microsomes from induced animal liver, CYP2B and CYP3A may contribute to both N-demethylation and 4-hydroxylation of antipyrine. PMID- 11785907 TI - Aldrin-induced locomotor activity: possible involvement of the central GABAergic cholinergic-dopaminergic interaction. AB - Aldrin (5 mg/kg/day, p.o.) under nontolerant condition, administered either for a single day or for 12 consecutive days, enhanced locomotor activity (LA) of rats. The increase in LA was greater in rats treated with aldrin for 12 consecutive days than that observed with a single dose. The aim of the present study is to evaluate the involvement of possible interactions of central GABAergic, cholinergic and dopaminergic systems using their agonist(s) and antagonist(s) in the regulation of LA in aldrin nontolerant rats. Administration of either L-DOPA along with carbidopa or bicuculline potentiated aldrin-induced increase in LA under nontolerant condition as well as LA of the control rats. Treatment with muscimol, haloperidol, atropine or physostigmine all decreased the LA of both aldrin nontolerant and control rats. Further, the application of (a) haloperidol along with bicuculline, atropine or physostigmine and (b) physostigmine along with bicuculline or L-DOPA + carbidopa significantly reduced LA but L-DOPA + carbidopa along with atropine or bicuculline increased LA of the control rats. These agonist(s)/antagonist(s)-induced decrease or increase in LA of the control rats were attenuated or potentiated, respectively, when those agonist(s)/antagonist(s) under abovementioned condition were administered to aldrin nontolerant rats. The attenuating or potentiating effects of aldrin on agonist(s)/antagonist(s) (either individually or in different combinations) induced change in LA were greater in rats treated with aldrin for 12 consecutive days than that observed with a single-dose aldrin treatment. These results suggest that aldrin, under nontolerant condition, reduces central GABAergic activity and increases LA by activating dopaminergic system via inhibition of cholinergic activity. The treatment with aldrin for 12 consecutive days produces greater effect than that caused by a single-day treatment. PMID- 11785908 TI - Myotropic effects of new proctolin analogues modified in the position 5 of peptide chain in insects. AB - To explain the role of the Thr5 residue of proctolin (Arg-Tyr-Leu-Pro-Thr) in the myotropic activity of this insect neuropeptide, we synthesized two groups of its analogues: 1) Arg-Tyr-Leu-Pro-X-OH with X = Val (1), D-Val (2), Ile (3), D-Ile (4), Ala (5), D-Ala (6), Asn (7), Gln (8), Ser (9), Pro (10), Phe (11), Asp (12), Glu (13), Arg (14), D-Arg (15), Lys (16) and Gly (17) and 2) Arg-Tyr-Leu-Pro-R', where R' = isobutylamine (18), S-1-methyl-1-phenylmethylamine (19), R-1-methyl-1 phenylmethylamine (20), R-2-amino-1-propanol (21), S-2-amino-1-propanol (22), R-1 amino-2-propanol (23), S-2-amino-1-propanol (24), 3-amino-1-propanol (25). Decapeptide proctolylproctolin (H-Arg-Tyr-Leu-Pro-Thr-Arg-Tyr-Leu-Pro-Thr-OH) (26) was synthesized. Syntheses of these peptides were carried out by solid-phase method. All peptides were bioassayed in vitro on the semi-isolated hearts of Tenebrio molitor using a cardioexcitatory test and on the foregut of locust (Schistocerca gregaria). Peptides 1, 3, 5, 9, 13, 14, 16, 22, and 23 retained about 30-50% of the cardioexcitatory activity in T. molitor. Analogues 1 and 3 preserved about 50% and analogue 8 about 80% of the myotropic activity, whereas compound 4 and 9 showed a very weak contractile activity in S. gregaria. PMID- 11785909 TI - Effect of glucocorticoid dexamethasone on cyclic AMP formation stimulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in the cerebral cortex and hypothalamus of chick. AB - In this study we tested in chicks the effects of acute and chronic in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, i.p.) on PACAP-stimulated cyclic AMP formation in [3H]adenine-prelabeled slices of the hypothalamus and cerebral cortex. PACAP (1-100 nM) concentration-dependently stimulated cyclic AMP formation in both brain regions of chick. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2, 24 and 48 h; while in chronic experiment the glucocorticoid was given once daily for 12 days and the animals were killed 48 h after the last injection. The ability of PACAP to stimulate cyclic AMP formation in the hypothalamus and cerebral cortex was similar in vehicle-treated (control) and dexamethasone-treated animals, with the exception of the nucleotide response to 100 nM of the peptide in both brain regions, which was significantly larger in the group of chicks killed 48 h after the administration of the single steroid dose. PMID- 11785910 TI - NMDA antagonists inhibit the development of ethanol dependence in rats. AB - The influence of non-competitive NMDA receptor antagonist, 1-amino-3,5-dimethyl adamantane (memantine), and glycineB site antagonist, 7-chloro-4-hydroxy-3-(3 phenoxy)phenyl-2(1H)-quinolone (L-701,324), on the development of ethanol dependence was investigated in Wistar rats. The development of ethanol dependence was induced by intragastric administration of 20% w/v ethanol, three times a day at increasing doses. The results were quantified using withdrawal audiogenic seizures, 12 h after the last ethanol administration. Memantine (3.75 or 7.5 mg/kg) and L-701,324 (2.5 or 5 mg/kg), given before ethanol administration, prevented the development of ethanol dependence. Our results support the data that NMDA receptors are involved in the development of ethanol dependence. PMID- 11785911 TI - Propranolol prevents the development of venous thrombosis in rats by a platelet dependent mechanism. AB - To clarify if one of the most common antihypertensive drugs, propranolol, can prevent venous thrombotic process, rats were treated with propranolol (PRO; 5 mg/kg i.p.) in an acute or chronic (14 days) manner. Both regimens resulted in a marked reduction of the systolic blood pressure (p < 0.001) and, probably as a consequence, in the shortening of the bleeding time (p < 0.01). After ligation of the vena cava, the incidence of the venous thrombosis and the thrombus weight decreased significantly in both propranolol-treated groups (p < 0.01) when compared to control rats. The antithrombotic effect of PRO was not accompanied by any changes in activated partial thromboplastin time, prothrombin time or euglobulin clot lysis time. However, long-term administfation of PRO resulted in a reduction of the ADP-induced platelet aggregation. PMID- 11785912 TI - Evaluation of interaction between valproate and baclofen in the formalin test in mice. AB - Valproate and baclofen dose-dependently inhibited both phases of the formalin test. Combination of valproate and baclofen exerted the additive antinociceptive effect on both phases of the formalin test. PMID- 11785913 TI - Neurochemical and pharmacological aspects of cocaine-induced seizures. AB - Seizures associated with cocaine intoxication are serious clinical problem requiring immediate and adequate treatment, however their mechanism has not been fully elucidated. In contrast to early views, which convulsive properties of cocaine ascribed predominantly to the effect of this drug on voltage-dependent sodium channels, recent reports put much emphasis on the interaction of cocaine with GABAergic and glutamatergic systems. Accordingly, pharmacological studies demonstrated that cocaine-induced seizures were efficiently inhibited by GABA-A receptor agonists and NMDA receptor antagonists, whereas sodium and calcium channel blockers were ineffective. An involvement of serotonin 5-HT2, dopamine and sigma receptors in cocaine-induced seizures has also been proposed. Furthermore, adaptive changes in various neuronal systems following cocaine induced seizures has been vigorously investigated. Some of those changes, such as expression of immediate early genes and increase in neuropeptide biosynthesis may play a compensatory anticonvulsive role, however, other alterations e.g. up regulation of NMDA receptors may increase susceptibility to seizures. This short review summarises recent advances in basic research on some neurochemical and pharmacological aspects of cocaine-induced seizures. PMID- 11785914 TI - Effect of antihormones in amygdala-kindled seizures in rats. AB - Tamoxifen (TXF; an antiestrogen), cyproterone acetate (CYP; an antiandrogen) and mifepristone (MIF; an antigestagen) did not affect kindling parameters (afterdischarge threshold, seizure severity, seizure duration and afterdischarge duration) in fully-kindled rats. TXF (50 mg/kg) and CYP (50 mg/kg), when combined with carbamazepine, or phenobarbital, both antiepileptics administered at their highest subprotective doses of 15 mg/kg, resulted in significant reduction of the seizure and afterdischarge durations, both in male and female rats. Additionally, the combination of carbamazepine and cyproterone markedly increased the afterdischarge threshold in fully-kindled rats of both genders. The interaction between antihormones and carbamazepine, or phenobarbital, was not reversed by the respective gonadal hormones (estradiol, progesterone, and testosterone), kainic acid, or strychnine. However, the TXF-, and CYP-induced effect on the action of carbamazepine was abolished by bicuculline, N-methyl-D-aspartic acid and aminophylline. The effect of TXF on the protective activity of phenobarbital was reversed by bicuculline and N-methyl-D-aspartic acid. Finally, the CYP-mediated effect on phenobarbital action was abolished by bicuculline and aminophylline. Neither TXF nor CYP altered free plasma levels and brain levels of carbamazepine or phenobarbital, so a pharmacokinetic interaction between antihormones and antiepileptic drugs is not probable. In view of the present data, it may be suggested that the protective activity of the antiestrogen and antiandrogen are mostly associated with the enhancement of GABA-ergic and purinergic transmission in the central nervous system. Also the augmentation of glutamatergic transmission, realized through NMDA receptors, may be involved in the mechanism of antiseizure action of TXF and CYP. PMID- 11785915 TI - Felbamate, gabapentin and topiramate as adjuvant antiepileptic drugs in experimental models of epilepsy. AB - Newly diagnosed epileptic patients start their medication with monotherapy. Around 30% of epileptic patients require more than one antiepileptic drug. Results from experimental studies provide evidence that administration of two antiepileptic drugs may result in antagonistic, additive, or supra-additive (synergistic) anticonvulsant effects. If adverse effects of a synergistic combination also show supra-additive summation then the protective index may not change. In this context, drug combinations, possessing synergistic anticonvulsant effects and additive (or infra-additive) toxicity, are of clinical interest. Recent experimental data indicate that topiramate and gabapentin generally potentiate the protective activity of conventional antiepileptic drugs against maximal electroshock-induced convulsions in mice. The anticonvulsant action of carbamazepine, diphenylhydantoin, phenobarbital, and valproate was not modified in this test by felbamate at subprotective doses against threshold electroconvulsions. Interestingly, conventional antiepileptics (at subeffective doses) enhanced the protection offered by felbamate. It may indicate that beneficial effects of a drug combination may be observed at only some drug ratios. PMID- 11785916 TI - Effect of adenosine receptor agonists on neurodegenerative and convulsive activity of mitochondrial toxin, 3-nitropropionic acid. AB - 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin inhibiting the activity of succinate dehydrogenase. Its experimental application in rodents causes lesions of the striatum resembling the course of Huntington's disease in humans. Recently, we have shown that 3-NPA is also a potent convulsive and proconvulsive agent. This study investigated the effects of adenosine receptor agonists on neurodegeneration and convulsions induced by 3-NPA. Adenosinergic agonists prevented seizures but not striatal neuronal loss evoked by 3-NPA, what suggests that different mechanisms might contribute to these pathologies associated with application of mitochondrial toxin. PMID- 11785917 TI - Brain tolerance and preconditioning. AB - In this review article the authors describe a phenomenon of "brain tolerance" which represents transient resistance of brain tissue to a lethal insult established by preconditioning with a mild insult of short duration. Tolerance evoked by brief ischemia resembles transient ischemic attack(s) (TIA) often preceding full-blown ischemic stroke in a clinical setting. A series of recent studies have described another relevant phenomenon termed "chemical preconditioning". Several substances interfering with cellular energy metabolism applied in subtoxic doses may provide protection against lethal insults of a different type. For example, 3-nitropropionic acid (3-NP), antibiotics erythromycin and kanamycin, acetylsalicylic acid, and 2-deoxyglucose have been shown to evoke tolerance. Recently, we have reported that NMDA receptor antagonists and 2-deoxyglucose used at relatively low doses were potent agents to potentiate the protective anticonvulsant effect induced by transient brain mild ischemia. Further studies are expected to prove similar action of these drugs in other experimental models. Based on the accumulated experimental and clinical data the brain tolerance subsequently reinforced by pharmacological intervention might become a successful prophylactic strategy against serious brain insults in patients. PMID- 11785918 TI - Previous prolonged clonic seizures diminish antiepileptic activity of valproate against pentetrazol-evoked convulsions. AB - Prolonged seizures may alter the brain function in numerous ways. It is conceivable that they might lead to modifications of seizure susceptibility or anticonvulsive drug efficacy, however, only limited data address this issue. Therefore, we have decided to estimate the antiepileptic activity of drugs interfering with GABA-ergic neurotransmission in mice subjected to prolonged clonic seizures 2 weeks before, using pentetrazol test. The activity of valproate, but not diazepam or phenobarbital, was diminished in animals following repetitive clonic seizures. It might be hypothesized that in humans suffering from epilepsy, prolonged seizures in the past might contribute to the lowered efficacy of valproic acid later on. PMID- 11785919 TI - Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice. AB - Clinical observations indicate that seizures induced by hypoxia are common kind of convulsive activity in both infants and elderly patients. The occurrence of seizure episode during hypoxia is important risk factor of epilepsy development in the future. Experimental hypoxia was obtained by exposure of adult (20-23 g) Albino Swiss mice to spontaneous breathing in gas mixture composed of 5% oxygen and 95% nitrogen. The latency time to convulsive activity was determined. Single sublethal episode of seizures induced by hypoxia (HS) resulted in higher susceptibility to pentetrazol (PTZ), bicuculline (BCC), N-methyl-D-aspartic acid (NMDA) but not in electrically induced convulsions. Adenosine A1 receptor agonist, R(-)N6-(2-phenyl-isopropyl)adenosine (R-PIA) (0.01; 0.05; 0.1 mg/kg, i.p.) prolonged the latency to HS-induced convulsions. A1 receptor antagonist, 8 cyclopentyltheophylline (CPT), reversed the protective action of R-PIA. A2 receptor agonist, N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]ethyladenosine (DPMA), only at the highest dose (5 mg/kg i.p.) prolonged the latency time to convulsive activity. This effect was only partially reversed by A2 antagonist 3,7 dimethyl-1-propargylxanthine (DMPX). Administered immediately after episode of HS R-PIA diminished the higher susceptibility to PTZ, BCC, NMDA at 3rd day after HS, while DPMA appeared to be ineffective. These results confirm the important role of adenosine A1 receptor agonist in protection against acute and chronic epileptogenic effect of hypoxia. The role of adenosine A2 receptors seems to be of minor importance. PMID- 11785920 TI - Influence of chronic treatment with H1 receptor antagonists on the anticonvulsant activity of antiepileptic drugs. AB - The aim of this study was to evaluate the effects of chronic astemizole and ketotifen administration on the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced convulsions in mice. Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain and plasma levels of antiepileptics were measured by immunofluorescence. Astemizole (2 mg/kg) and ketotifen (8 mg/kg) significantly diminished the electroconvulsive threshold, being without effect upon this parameter at lower doses. Astemizole significantly reduced the anticonvulsant action of phenobarbital and diphenylhydantoin, but it did not affect that of carbamazepine and valproate. Moreover, ketotifen (at the subprotective dose of 4 mg/kg) remained without effect upon the protective activity of valproate, diphenylhydantoin or phenobarbital, but significantly diminished the anticonvulsant effect of carbamazepine. Histamine receptor antagonists combined with antiepileptic drugs, did not alter their brain and free plasma levels. Also, they did not influence adverse potential of carbamazepine, diphenylhydantoin and valproate while that of phenobarbital was significantly enhanced. Valproate, phenobarbital and diphenylhydantoin alone at their ED50s against maximal electroshock or combined with the histamine receptor antagonists disturbed long term memory. The results of this study indicate that H1 receptor antagonists, should be used with caution in epileptic patients. PMID- 11785921 TI - Drug addiction. Part I. Psychoactive substances in the past and presence. AB - Substances capable of changing the functions of the central nervous system are widely distributed in plant kingdom, and many of them were discovered by ancient food-gatherers at the dawn of humanity. In the Old World only a few substances producing euphoria or altered states of consciousness and having habit-forming properties are still widely used. They are the products of poppy (opium, morphine), hemp (hashish, marijuana), and of fermentation of various organic materials alkohol. This list has recently been joined by the psilocybin containing mushrooms. The addiction-forming compounds originated in the New World and widely spread are tobacco (nicotine) and cocaine. In the 19th and 20th, century the development of medicinal chemistry resulted in several synthetic compounds, originally proposed as therapeutics, such as barbiturates, benzodiazepines and amphetamines. Due to legal problems, to avoid production of the substances already prohibited, many designer drugs were manufactured. In addition, several compounds were synthesized as recreational drugs. Also some compounds that were not regarded as drugs, such as aromatic hydrocarbons and other cleansing agents, as well as steroids were found to have properties of dangerous, habit-forming agents. The attitude of society and the pattern of use of psychoactive substances have changed with time, particularly in the last decades. The active principles are now more addictive because of concentration, purification, chemical modifications and the way of ingestion, which now favors most rapid transport to the central nervous system. The substance abuse approaches the level of global epidemics, and the recent usage of drugs of addition is also reviewed. PMID- 11785922 TI - Biosynthesis and biological properties of compounds containing highly reactive, reduced sulfane sulfur. AB - The covalent modifications of sulfhydryl groups (-SH) may occur through oxidation to mixed disulfides (S-thiolation), S-nitrosylation, as well as persulfide and trisulfide formation. The latter possibilities of -SH group modification connected with compounds containing sulfur called sulfane sulfur are described in this paper. Sulfane sulfur compounds contain a labile, highly reactive sulfur atom at a reduced oxidation state with a valence of 0 or -1, covalently bound to another sulfur atom. These compounds include persulfides, polysulfides, polythionates, thiosulfate, elemental sulfur and disulfides, which enable tautomerization to thiosulfoxides. Sulfane sulfur compounds are formed in the anaerobic cysteine sulfur metabolism with the participation of such enzymes as cystathionase (CST), 3-mercaptopyruvate sulfurtransferase (MpST) and rhodanese (thiosulfate: cyanide sulfurtransferase). Compounds containing sulfane sulfur participate in cell regulation processes through activation or inactivation of some enzymes. Other important roles of sulfane sulfur compounds are their antioxidative properties, significance in the processes of carcinogenesis, participation in the tRNA sulfuration as well as an influence on the activity of immune cells. To recognize completely the biological role of compounds with sulfane sulfur it is necessary to have sensitive methods of quantitative determination, so a review of these methods is presented in this paper. Moreover, biosynthetic pathways and biological properties of these compounds have been discussed. PMID- 11785923 TI - Reversal of stress-induced memory changes by moclobemide: the role of neurotransmitters. AB - Studies on animals have shown that chronic stress is able to evoke behavioral changes such as locomotor activity deficit, decreased sleep, reduced food and water consumption and impaired memory. Chronic stress produces changes in concentrations of neurotransmitters, mainly in the hippocampus. The hippocampus is a vulnerable brain structure that is involved in learning and memory functions. In this study, we investigated the effects of chronic stress procedure and moclobemide in rats, and the influence of chronic stress on the levels of monoamines: noradrenaline (NE), dopamine (DA) and serotonin (5-HT) in the rat hippocampus [as well as their metabolites: dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA)]. It was found out that chronic 21-day stress caused worsening of memory: the well trained rats after stress procedure lost their ability to find food quickly. Because of many errors in finding the way, the time these animals needed was on average 2.4-times longer than that of the control group. Single, as well as prolonged (21 days) treatment with moclobemide (10 mg/kg/day) counteracted the deficit of memory induced by chronic stress. In stressed animals, we observed an increase in DA, decrease in DOPAC, 5-HT and 5 HIAA and decrease in NE levels. Moclobemide modulated the changes in the levels of neurotransmitters in the hippocampus, decreasing their turnover. The results demonstrate that moclobemide improves memory impaired by stress. They suggest also that moclobemide has a modulatory effect on stress-induced neurotransmitter changes which may be of importance for the protective effect of the drug with regard to memory impairment. PMID- 11785924 TI - Examination of the influence of 3,5-DHPG on behavioral activity of angiotensin II. AB - The effects of the class I metabotropic glutamate receptor (mGluR) stimulation on the behavioral activity of angiotensin II (Ang II) was investigated in the present study. The experiments were performed on adult male Wistar rats. Stimulation of the group I of mGluR receptors was evoked by icv injection of (S) 3,5-dihydroxyphenylglycine (3,5-DHPG) at the dose of 0.01 and 1 nmol per rat. Fifteen minutes later, the animals were given icv solution containing 1 nmol of Ang II. Memory motivated affectively was evaluated in passive avoidance and active avoidance responses (CARs). Moreover, the speculative influence of the treatment on anxiety and motor activity was tested in elevated plus-maze and in open field, respectively. We observed that both compounds did not have statistically significant influence on motor activity of rats in open field test. However, 3,5-DHPG at the dose of 0.01 nmol given alone and combined with Ang II tended to increase locomotor activity. 3,5-DHPG, given alone, significantly facilitated consolidation process in a passive avoidance situation (only at the dose of 0.01 nmol) but had no influence on acquisition and recall of information. Examination of the influence of 3,5-DHPG on the acquisition and extinction of CAR proved that it did not alter acquisition and extinction of these responses. In the elevated plus-maze, 3,5-DHPG had anxiogenic-like profile. Ang II, as repeatedly shown before, greatly increased passive avoidance latency, rate of acquisition of CARs and decreased their extinction. On the other hand, Ang II induced anxiolytic-like effect in elevated plus-maze. The pre-treatment of rats with 3,5-DHPG tended to attenuate behavioral effects of the Ang II administration. PMID- 11785925 TI - AIDA influences behavior in rats pretreated with baclofen. AB - The influence of the blockade of group I metabotropic glutamate receptors (I mGluRs) by AIDA on some behavioral effects of rats pretreated with baclofen, an agonist of GABA-B receptor, was investigated using behavioral tests: the open field, the passive avoidance response and the elevated "plus" maze. Baclofen, applied intraperitoneally (ip) at a dose of 0.25 mg/kg, increased the number of crossed fields and bar approaches in rats in the open field test, and prolonged the time spent in the closed arms, shortened the time spent in the open arms and decreased the number of entries to the open arms in the elevated "plus" maze, but did not affect retrieval in the passive avoidance response. AIDA administered intracerebroventricularly (icv) alone at a dose of 100 nmol reduced crossings and rearings in the open field test, however, it had no effect on retrieval in the passive avoidance situation, nor did it show any influence in the elevated "plus" maze. AIDA given 15 min after baclofen significantly decreased mobility of rats (in the case of crossings to the level observed when AIDA was given alone), i.e. AIDA changed the effects of baclofen in the open field test. We also noted significant impairment of retrieval in rats pretreated with baclofen, which later received AIDA. AIDA significantly reduced the effect of baclofen on this memory process. In the elevated "plus" maze test, AIDA did not influence the behavior of rats pretreated with baclofen in comparison with the group treated with baclofen alone. PMID- 11785926 TI - Influence of doxepin used in preemptive analgesia on the nociception in the perioperative period. Experimental and clinical study. AB - The aim of the present research was to assess in experimental and clinical study the influence of doxepin administered intraperitoneally (ip) as preemptive analgesia on the nociception in the perioperative period. The pain thresholds for mechanical stimuli were measured in rats. The objective of clinical investigation was to assess the influence of preemptive administration of doxepin on postoperative pain intensity, analgesic requirement in the early postoperative period as well as an assessment of the quality of postoperative analgesia by the patient. Doxepin injected ip (3-30 mg/kg) dose-dependently increased the pain threshold for mechanical stimuli measured in paw pressure test in rats. Doxepin injected 30 min before formalin significantly increased the nociceptive threshold in the paw pressure test. In contrast, doxepin injected 240 min before formalin or 10 min after formalin did not change the nociceptive threshold. Morphine administered subcutaneously (sc) at a dose of 1 mg/kg increased the pain threshold measured in the paw pressure test 55 min after formalin treatment. Injection of 10 mg/kg of doxepin 30 min before formalin further enhanced the response after morphine administration. The results of the clinical study demonstrated that the patients who were administered doxepin preemptively showed significantly lower pethidine requirement in order to achieve a similar level of postoperative analgesia. The results of the research under discussion confirm the theoretical assumptions that there is a possibility to modify the nociception process in the perioperative period through preemptive analgesia using a drug that modifies the activity of the descending antinociceptive system. PMID- 11785927 TI - Behavioral changes in the course of chronic renal insufficiency in rats. AB - In addition to the changes in various biochemical parameters chronic renal insufficiency (CRI) leads to progressive behavioral disturbances both in humans and rats. To further characterize these changes, the present study aimed to investigate locomotor, exploratory and emotional activity of rats with experimental CRI. Our experiments with the open field test have shown a marked decrease in locomotor, exploratory and emotional activity of the animals suffering from CRI. These changes were parallel with an increased water intake, reduced food intake and body weight. Thus, behavioral disturbances accompanying CRI in rats are similar to those occurring in human patients. The experimental model of CRI described by us seems to be a good tool for pharmacological studies. PMID- 11785928 TI - Ischemic and reperfusive release of the endogenous purines and its influence on the myocardial viability during beta-adrenergic blockade. AB - The aim of this study was to estimate ischemic and reperfusive release of myocardial adenosine degradation products (MADP) during beta-adrenergic blockade and its relation to infarct size (IS) and viable myocardium size (VM). In a group of 24 shepherd-mongrel dogs, randomly assigned to a metoprolol (M-) and placebo group (P-group), occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion with recombinant tissue plasminogen activator was performed. Regional myocardial blood flow (MBF) was measured by the radiolabelled microsphere technique. Blood samples from aorta and great cardiac vein were collected to evaluate the concentrations of MADP. The triphenyltetrazolium chloride perfusion and fixation technique was used for infarct size measurement. MBF in the area at risk decreased in both groups during ischemia, but it was significantly higher (p = 0.013) in M-group. Recanalization of LAD was associated with an increase in flow in postischemic vascular bed. MBF was significantly higher (p = 0.024) in P-group during late reperfusion. In M-group IS was smaller (p = 0.007) and VM was bigger (p = 0.007). The correlation between arterial adenosine concentration during early reperfusion and IS (p = 0.044, r = -0.588) or VM (p = 0.036, r = 0.607) in M-group was noted. Values of net MADP balances significantly increased during early reperfusion. The correlation between reperfusive net MADP balance and IS (p = 0.00005, r = 0.906) or VM (p = 0.016, r = -0.675) in M-group was observed. The amount of MADP released during reperfusion correlates with the IS and is inversely proportional to the area of VM. The endogenously released adenosine may have additional cardioprotective effect during beta-adrenergic blockade. PMID- 11785929 TI - L-proline analogues of anthraquinone-2-carboxylic acid: cytotoxic activity in breast cancer MCF-7 cells and inhibitory activity against topoisomerase I and II. AB - A series of proline analogues of anthraquinone-2-carboxylic acid (1-3) were synthesized and evaluated for cytotoxic activity in the cultured breast cancer MCF-7 cells. The concentrations of 1, 2 and 3 needed to inhibit [3H]thymidine incorporation into DNA by 50% (IC50) were found to be 107 +/- 6 microM, 185 +/- 5 microM and 87 +/- 6 microM, respectively. To test whether cytotoxic properties were related to topoisomerase action, the most potent compounds 1 and 3 were evaluated in a cell-free system. Compound 3, which contains a basic substituent at C terminus of the amino acid such as (dimethylamino)propyl inhibited the catalytic activity of both topoisomerases I and II at a concentration of 30 and 60 microM, respectively. However, compound 1 containing an electrostatically neutral moiety, such as methyl ester did not inhibit topoisomerase I or topoisomerase II. In summary, compound 3 is a promising lead compound for a further structural variation in the design of new antitumour drugs. PMID- 11785930 TI - Lack of a modulatory effect of imipramine on glucocorticoid-induced suppression of interferon-gamma and interleukin-10 production in vitro. AB - Antidepressant drugs have been shown to reverse some changes evoked by glucocorticoids or stress. In the present study we attempted to find out whether imipramine, one of the most frequently used antidepressant drugs, interfered with glucocorticoids, modulating the production of IFN-gamma and IL-10, pro inflammatory and anti-inflammatory cytokines, respectively. We observed a significant inhibitory effect of hydrocortisone, dexamethasone and the glucocorticoid receptor agonist RU 28362, used at doses of 10(-6) and 10(-5) M, on the production of IFN-gamma and IL-10 by whole blood cells stimulated by mitogens. Imipramine at doses of 10(-6) and 10(-5) M did not modulate IFN-gamma or IL-10 production, whereas at a dose of 10(-5) M it increased the production of IL- 10 and decreased that of IFN-gamma, those results being statistically insignificant, though. A combination of imipramine and dexamethasone or hydrocortisone at doses of 10(-6) or 10(-5) M significantly suppressed the production of IFN-gamma and IL-10, the level of inhibition being similar to that observed for glucocorticoids alone. The classic antidepressant imipramine was not able to modulate the suppressive effect of "stress" doses of hydrocortisone on the production of cytokines. PMID- 11785931 TI - Plant callose synthase complexes. AB - Synthesis of callose (beta-1,3-glucan) in plants has been a topic of much debate over the past several decades. Callose synthase could not be purified to homogeneity and most partially purified cellulose synthase preparations yielded beta-1,3-glucan in vitro, leading to the interpretation that cellulose synthase might be able to synthesize callose. While a rapid progress has been made on the genes involved in cellulose synthesis in the past five years, identification of genes for callose synthases has proven difficult because cognate genes had not been identified in other organisms. An Arabidopsis gene encoding a putative cell plate-specific callose synthase catalytic subunit (CalS1) was recently cloned. CalS1 shares high sequence homology with the well-characterized yeast beta-1,3 glucan synthase and transgenic plant cells over-expressing CalS1 display higher callose synthase activity and accumulate more callose. The callose synthase complex exists in at least two distinct forms in different tissues and interacts with phragmoplastin. UDP-glucose transferase, Rop1 and, possibly, annexin. There are 12 CalS isozymes in Arabidopsis, and each may be tissue-specific and/or regulated under different physiological conditions responding to biotic and abiotic stresses. PMID- 11785932 TI - Early genes responsive to abscisic acid during heterophyllous induction in Marsilea quadrifolia. AB - The aquatic fern Marsilea quadrifolia produces different types of leaves in response to changes in natural environment and culture conditions. When the conditions are in favor of producing the submerged-type leaves, exogenous application of the plant hormone abscisic acid (ABA) induces the formation of aerial-type leaves. Tissues responsive to ABA were localized to the shoot apical meristem and the associated organ primordia. From these tissues, at least two tiers of ABA-regulated early genes were identified, including seven primary genes and seventeen secondary genes. These genes, designated ABRH for ABA-responsive heterophylly, showed diverse expression patterns during the course of heterophyllous induction. Changes in the transcript level of ABRH genes started early, within 0.5-1.0 h after the addition of ABA to the culture medium. Some changes were transient while the others were persistent. The ABRHs contain extensive sequence homology to known genes, including those encoding transcription factors, protein kinases, membrane transporters, metabolic enzymes, structural proteins and those encoded by the chloroplast genome. Identification of these ABRHs is a first step toward the understanding of the regulation mechanisms of heterophylly, and the results suggest the involvement of novel metabolic and regulatory pathways in ABA-controlled morphogenesis. PMID- 11785933 TI - Characterization of a novel plant acyl-coA synthetase that is expressed in lipogenic tissues of Brassica napus L. AB - A cDNA encoding a novel isoform of acyl-CoA synthetase (ACS6) was isolated from embryos of oilseed rape. Homology searches show it is most closely related to ACS4 from rat and human brain rather than the other oilseed rape ACSs. The ACS6 is strongly expressed in embryos and flowers, tissues of Brassica napus that synthesize lipids at high rates. The activity of recombinantly expressed ACS6 was recovered in the insoluble fraction (214,000 x g, 1 h pellet). CHAPS-solubilized recombinant ACS6 protein preferred utilising long-chain fatty acids that contained a cis-9 double bond, i.e. palmitoleic, oleic, linoleic and linolenic acids. Western blot analysis showed that the ACS6 protein is membrane-bound. PMID- 11785934 TI - A proteinase inhibitor II of Solanum americanum is expressed in phloem. AB - Although proteinase inhibitor proteins are known to confer insect resistance in transgenic plants, their endogenous roles remain undefined. Here, we describe the expression of a proteinase inhibitor II (PIN2) protein from Solanum americanum in phloem of stems, roots and leaves suggesting a novel endogenous role for PIN2 in phloem. The phloem consists of parenchyma cells, sieve elements (SE), and companion cells (CC) which are in close association with SE. We isolated two cDNAs encoding PIN2, SaPIN2a and SaPIN2b, from a S. americanum cDNA library using a tomato PIN2 cDNA as hybridization probe. SaPIN2a shows 73.6% identity to SaPIN2b. Southern blot analysis confirmed that two genes occur in S. americanum. Northern blot analysis showed that both are wound-inducible and are expressed in flowers. Unlike SaPIN2b and other previously characterized plant PIN2 proteins, SaPlN2a is abundantly expressed in stems. In situ hybridization studies on stem sections showed that SaPIN2a mRNA is expressed in CC and some SE, likely the immature developing SE. of external and internal phloem. Western blot analysis using SaPIN2a-specific antibodies showed SaPIN2a accumulation in stems, leaf midribs and fruits. Immunohistochemical localization, using these antibodies, revealed SaPIN2a expression in external and internal phloem of stem. Immunoelectron microscopy of stem, root and leaf sections further localized SaPIN2a to the CC and predominantly to the SE, particularly the parietal cytoplasm adjacent to the cell wall, the lumen and the sieve-area pores. These results suggest that, other than a possible role in plant defense, SaPIN2a could be involved in regulating proteolysis in the SE. PMID- 11785935 TI - Differential expression of putative cell death regulator genes in near-isogenic, resistant and susceptible barley lines during interaction with the powdery mildew fungus. AB - We analysed pathogenesis-related expression of genes, that are assumed to be involved in ubiquitous plant defence mechanisms like the oxidative burst, the hypersensitive cell death reaction (HR) and formation of localized cell wall appositions (papillae). We carried out comparative northern blot and RT-PCR studies with near-isogenic barley (Hordeum vulgareL. cv. Pallas) lines (NILs) resistant or susceptible to the powdery mildew fungus race A6 (Blumeria graminis f.sp. hordei, BghA6). The NILs carrying one of the R-genes Mla12, Mlg or the mlo mutant allele mlo5 arrest fungal development by cell wall appositions (mlo5) or a HR (Mla12) or both (Mlg). Expression of an aspartate protease gene, an ascorbate peroxidase gene and a newly identified cysteine protease gene was up-regulated after inoculation with BghA6, whereas the constitutive expression-level of a BAS gene, that encodes an alkyl hydroperoxide reductase, was reduced. Expression of a newly identified barley homologue of a mammalian cell death regulator, Bax inhibitor 1, was enhanced after powdery mildew inoculation. An oxalate oxidase like protein was stronger expressed in NILS expressing penetration resistance. A so far unknown gene that putatively encodes the large subunit of a superoxide generating NADPH oxidases was constitutively expressed in barley leaves and its expression pattern did not change after inoculation. A newly identified barley Rac1 homologue was expressed constitutively, such as the functionally linked NADPH oxidase gene. Gene expression patterns are discussed with regard to defence mechanisms and signal transduction. PMID- 11785936 TI - The nodulin vfENOD18 is an ATP-binding protein in infected cells of Vicia faba L. nodules. AB - Recently we described the novel nodulin gene VfENOD18, whose corresponding transcripts were restricted to the nitrogen-fixing zone III of broad bean root nodules. To characterize VfENOD18 on the protein level, polyclonal antibodies were generated using the purified recombinant VfENOD18 protein produced in Escherichia coli by employing the pMAL-c expression system. These antibodies recognized immunoreactive proteins isolated from indeterminate nodules of different leguminous plants, but also from non-symbiotic tissues of Glycine max and from tissues of Arabidopsis thaliana and Zea mays. Using immunogold labelling the nodulin VfENOD18 was localized to the cytoplasm of infected cells in the nitrogen-fixing zone of broad bean nodules. Due to the homology of the VfENOD18 sequence to that of the ATP-binding protein MJ0577 from the hyperthermophile Methanococcus jannaschii the recombinant VfENOD18 protein was tested for ATP binding. Using the biotin photoaffinity ATP analogue 8N3ATP[gamma]biotin it could be demonstrated that VfENOD18 is an ATP-binding protein. PCR experiments revealed that the amino acid sequences of the putative C-terminal ATP-binding sites of the VfENOD 18 homologues from Lens culinaris, Vicia hirsuta, Vicia sativa and Vicia villosa were conserved. We propose that VfENOD18 is a member of a novel family of ATP-binding proteins in plants. PMID- 11785937 TI - Cloning and characterization of a DEAD box RNA helicase from the viable seedlings of aged mung bean. AB - Seeds stored under adverse conditions will reduce the viability of germination as a result of induced aging. We have established a procedure to induce accelerated aging for studying the process of aging in mung bean (Vigna radiata) seeds at the molecular level. A full-length cDNA was isolated from acceleratedly aged mung bean seedlings. The cDNA, VrRH1 (Vigna radiata RNA helicase 1), contains an open reading frame of 2139 bp encoding a protein of 713 amino acids. VrRHI has seven highly conserved motifs including the DEAD box as in the case of other plant RNA helicases. VrRHI was sub-cloned into an expression vector pET-28b (+), over expressed in Escherichia coli BL 21 and purified by a Ni2+-agarose column. The expressed protein showed double-stranded RNA unwinding and ATPase activities. Either ATP or dATP is required for the unwinding activity, indicating that VrRHI is an ATP/dATP-dependent RNA helicase. Northern blot analysis showed the presence of mRNAs hybridized with a full-length cDNA fragment of VrRHI (VrRH transcripts) in mung bean seeds that were imbibed for 16 to 32 h after accelerated aging treatment. The amount of these mRNAs reached a maximum in 24 h imbibed seeds after the treatment. The accumulation of VrRH transcripts was shown to lead to the appearance of 25S and 18S rRNAs in the imbibed aging mung bean seeds. The results suggest that VrRHI may play a role in the viability of mung bean seeds. PMID- 11785938 TI - Identification of a S-ribonuclease-binding protein in Petunia hybrida. AB - To investigate protein-protein interactions in gametophytic self-incompatibility, we used a yeast two-hybrid assay to identify proteins that could interact with the S-ribonuclease protein. These assays identified a pollen-expressed protein, which we have named PhSBP1, that appears to bind with a high degree of specificity to the Petunia hybrida S-ribonuclease. Although PhSBP1 activates reporter gene expression only when expressed in tandem with a S-RNAse bait protein, binding is not allele-specific. Sequence analysis demonstrated that PhSBP1 contained a C-terminal cysteine-rich region that includes a RING-HC domain. Because many RING-finger domain proteins appear to function as E3 ubiquitin ligases, our results suggest that ubiquitination and protein degradation may play a role in regulating self-incompatibility interactions. Together, these results suggest that PhSBPI may be a candidate for the recently proposed general inhibitor (RI) of self-incompatibility ribonucleases. PMID- 11785939 TI - Identification and molecular characterisation of hordoindolines from barley grain. AB - Grain texture in barley is an important quality character as soft-textured cultivars have better malting quality. In wheat, texture is considered to be determined by the puroindolines, a group of basic hydrophobic proteins present on the surface of the starch granule. Hard wheats have been proposed to lack puroindoline a or to have mutant forms of puroindoline b which do not bind to the granule surface. Analysis of six barley cultivars (three soft-textured and three hard) showed that all contained proteins homologous to wheat puroindoline b, but PCR analysis failed to show any differences in amino acid sequences similar to those which have been proposed to determine textural differences in wheat. Southern blot analysis showed two hordoindoline b genes which were isolated and shown to encode proteins with 94% sequence identity. Expression of hordoindoline b mRNA occurred in the starchy endosperm and aleurone layer of the developing seed, but not in the embryo. Analysis of seven soft- and six hard-textured barley varieties showed that all contained hordoindoline a except two hard varieties (Sundance, Hart) which were subsequently shown to both lack hordoindoline a mRNA. It was therefore concluded that there is not a clear relationship between the presence of hordoindoline a and grain texture in barley. PMID- 11785940 TI - An OGG1 orthologue encoding a functional 8-oxoguanine DNA glycosylase/lyase in Arabidopsis thaliana. AB - Repair of the ubiquitous mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoG) is initiated in eukaryotes by DNA glycosylases/lyases, such as yeast Ogg1, that do not share significant sequence identity with their prokaryotic counterparts, typified by Escherichia coli MutM (Fpg) protein. The unexpected presence of a functional mutM orthologue in the model plant Arabidopsis thaliana has brought into question the existence of functional OGG1 orthologues in plants. We report here the cDNA cloning, expression and functional characterization of AtOGG1, an Arabidopsis thaliana gene widely expressed in different plant tissues which encodes a 40.3 kDa protein with significant sequence identity to yeast and human Ogg1 proteins. Purified AtOgg1 enzyme specifically cleaves duplex DNA containing an 8-OxoG:C mispair, and the repair reaction proceeds through an imine intermediate PMID- 11785941 TI - POR C of Arabidopsis thaliana: a third light- and NADPH-dependent protochlorophyllide oxidoreductase that is differentially regulated by light. AB - During the sequencing of the genome of Arabidopsis thaliana a gene has been identified that encodes a novel NADPH-protochlorophyllide oxidoreductase (POR) like protein (accession number AC 002560). This protein has been named POR C. We have expressed the POR C protein in Escherichia coli and have determined its in vitro activity. POR C shows the characteristics of a light-dependent and NADPH requiring POR similar to POR A and POR B. The expression of the POR C gene differs markedly from that of the POR A and POR B genes. In contrast to the POR A and POR B mRNAs, the POR C mRNA has been shown previously to accumulate only after the beginning of illumination. In light-adapted mature plants only POR B and POR C mRNAs were detectable. The amounts of both mRNAs show pronounced diurnal rhythmic fluctuations. While the oscillations of POR B mRNA are under the control of the circadian clock, those of POR C mRNA are not. Another difference between POR B and POR C was found in seedlings that were grown under continuous white light. The concentration of POR C mRNA rapidly declined and soon dropped beyond the limit of detection, after these seedlings were transferred to the dark. On the other hand. POR B mRNA was unaffected by this light/dark shift. When seedlings were exposed to different light intensities, the amounts of POR B mRNA remained the same, while POR A and POR C mRNAs were modulated in an inverse way by these light intensity changes. POR A mRNA was still detectable in seedlings grown under low light intensities but disappeared at higher light intensities, while the mRNA concentration of POR C rose with increasing light intensities. These different responses to light suggest that the functions of the three PORs of Arabidopsis are not completely redundant, but may allow the plant to adapt its needs for chlorophyll biosynthesis more selectively by using preferentially one of the three enzymes under a given light regime. PMID- 11785942 TI - L and D presequence peptides derived from the precursor of F1beta subunit of the ATP synthase inhibit mitochondrial protein import by interaction with import machinery. AB - We investigated the effect of L and D enantiomers of a 25-residue peptide derived from the N-terminal region of the presequence of Nicotiana plumbaginifolia F1beta subunit of the ATP synthase, pF1beta(1, 25), on import into spinach leaf mitochondria. Three in vitro synthesized precursor proteins using different import pathways were used. Import of the precursor proteins of F1beta subunit of the ATP synthase, pre-F1beta, and the alternative oxidase, pre-AOX, required addition of external ATP. whereas the chimeric precursor containing the N terminal 84 amino acids of the cytochrome b2 precursor protein linked to dihydrofolate reductase, pre-b2(1, 84)-DHFR was not dependent on ATP. Import of pre-F1beta, and pre-AOX was inhibited already at 1 microM and 3 microM concentration of the L and D enantiomers, whereas inhibition of import of pre b2(1, 84)-DHFR, occurred at concentrations >10 microM of both enantiomers. Binding efficiency of the precursor proteins was not affected by addition of the L and D enantiomers. There was no correlation between inhibition of import of pre F1beta and pre-AOX and dissipation of membrane potential measured as a decrease of Rhodamine 123 fluorescence quenching. The inhibitory effect of the L and D presequence enantiomers on import of pre-F1beta and pre-AOX was concluded to occur within the outer membrane translocase machinery beyond the initial precursor receptor interaction. Furthermore, the fact that the D enantiomer had the same effect as the natural peptide showed that interaction of the presequence with the import machinery was not dependent on chiral properties of the presequence. PMID- 11785943 TI - Calcium-binding proteins: intracellular sensors from the calmodulin superfamily. AB - In all eukaryotic cells, and particularly in neurons, Ca(2+) ions are important second messengers in a variety of cellular signaling pathways. In the retina, Ca(2+) modulation plays a crucial function in the development of the visual system's neuronal connectivity and a regulatory role in the conversion of the light signal received by photoreceptors into an electrical signal transmitted to the brain. Therefore, the study of retinal Ca(2+)-binding proteins, which frequently mediate Ca(2+) signaling, has given rise to the important discovery of two subfamilies of these proteins, neuronal Ca(2+)-binding proteins (NCBPs) and calcium-binding proteins (CaBPs), that display similarities to calmodulin (CaM). These and other Ca(2+)-binding proteins are integral components of cellular events controlled by Ca(2+). Some members of these subfamilies also play a vital role in signal transduction outside of the retina. The expansion of the CaM-like protein family reveals diversification among Ca(2+)-binding proteins that evolved on the basis of the classic molecule, CaM. A large number of NCBP and CaBP subfamily members would benefit from their potentially specialized role in Ca(2+) dependent cellular processes. Pinpointing the role of these proteins will be a challenging task for further research. PMID- 11785944 TI - Calcium-dependent oxidation of thioredoxin during cellular growth initiation. AB - The fraction of cell thiol proteins in the oxidized disulfide form were quantified during mitogen-induced HaCaT keratinocyte growth initiation. Oxidized thioredoxin increased from 11 +/- 1.2% in resting cells to 80 and 61% 2 min after addition of bradykinin or EGF. Thioredoxin oxidation was transient returning toward normal values by 20 min. The disulfide forms of other cellular proteins rose in parallel with thioredoxin oxidation. The oxidation of thioredoxin depended on a rise in cytosolic calcium. It was prevented by preloading cells with BAPTA, a Ca(2+) chelator and induced by addition of Ca(2+)-ionophore A23187 or of thapsigargin. In cell extracts, thioredoxin reductase was inhibited by micromolar calcium. The rise in cytosolic Ca(2+) led to a concomitant burst of H(2)O(2) formation. The oxidizing intracellular milieu suggests that redox regulation actively participates in the growth initiation cascade. The role of peroxiredoxins and ASK 1 cascade activation are discussed in this context. PMID- 11785945 TI - Demonstration of dimethylnonanoyl-CoA thioesterase activity in rat liver peroxisomes followed by purification and molecular cloning of the thioesterase involved. AB - Peroxisomes play an indispensable role in cellular fatty acid oxidation in higher eukaryotes by catalyzing the chain shortening of a distinct set of fatty acids and fatty acid derivatives including pristanic acid (2,6,10,14 tetramethylpentadecanoic acid). Earlier studies have shown that pristanic acid undergoes three cycles of beta-oxidation in peroxisomes to produce 4,8 dimethylnonanoyl-CoA (DMN-CoA) which is then transported to the mitochondria for full oxidation to CO(2) and H(2)O. In principle, this can be done via two different mechanisms in which DMN-CoA is either converted into the corresponding carnitine ester or hydrolyzed to 4,8-dimethylnonanoic acid plus CoASH. The latter pathway can only be operational if peroxisomes contain 4,8-dimethylnonanoyl-CoA thioesterase activity. In this paper we show that rat liver peroxisomes indeed contain 4,8-dimethylnonanoyl-CoA thioesterase activity. We have partially purified the enzyme involved from peroxisomes and identified the protein as the rat ortholog of a known human thioesterase using MALDI-TOF mass spectrometry in combination with the rat EST database. Heterologous expression studies in Escherichia coli established that the enzyme hydrolyzes not only DMN-CoA but also other branched-chain acyl-CoAs as well as straight-chain acyl-CoA-esters. Our data provide convincing evidence for the existence of the second pathway of acyl CoA transport from peroxisomes to mitochondria by hydrolysis of the CoA-ester in peroxisomes followed by transport of the free acid to mitochondria, reactivation to its CoA-ester, and oxidation to CO(2) and H(2)O. (c)2002 Elsevier Science. PMID- 11785946 TI - INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells. AB - Flow-cytometric fluorescence energy transfer (FCET) measurements between fluorescently labeled cell surface MHC-I and ICAM-1 molecules indicated similar receptor patterns in the plasma membrane of interferon-gamma (INF-gamma)-treated colon carcinoma cells as those observed earlier at the surface of lymphoid cells. INF-gamma activation significantly increased the density of MHC-I and ICAM-1 proteins in the membrane. This increase in receptor density was accompanied by decreased proximity level of the homo-associated MHC-I receptors. Hetero association of MHC-I and ICAM-1 molecules was increased by INF-gamma treatment. INF-gamma changed neither hetero- nor homo-association of transferrin receptors. By staining the sphingomyelin/cholesterol-enriched lipid microdomains with fluorescently labeled cholera toxin B subunit, we found an increase in the amount of lipid-raft associated G(M1)-gangliosides due to INF-gamma treatment. Confocal microscopic results and FCET measurements show that MHC-I and ICAM-1 are components of G(M1)-ganglioside containing lipid-rafts and also support an increase in the size of these lipid-rafts upon INF-gamma treatment. PMID- 11785947 TI - Cloning and expression of the rat vacuole membrane protein 1 (VMP1), a new gene activated in pancreas with acute pancreatitis, which promotes vacuole formation. AB - To characterize the emergency program set up by pancreatic cells in response to pancreatitis, we established the phenotype of the pancreatitis-affected pancreas by characterizing a large number of its transcripts. In this report, we describe the cloning, sequencing, and expression pattern of a new gene, named VMP1 (vacuole membrane protein 1). The VMP1 mRNA codes for a putative protein of 406 amino acids. In situ hybridization studies revealed that pancreatic expression of VMP1 mRNAs was restricted to the acinar cells. Interestingly, VMP1 mRNA was also overexpressed in kidney after transient ischemic injury. However, many healthy tissues express VMP1 mRNA. Structure analysis suggested that VMP1 is a transmembrane protein with six hydrophobic regions. VMP1/EGFP fusion protein was located to the Golgi apparatus and the endoplasmic reticulum area. Expression of this protein promoted the formation of intracytoplasmatic vacuoles and VMP1/EGFP was located to the membranes of these vacuoles. Cells overexpressing this protein died after 48 h. In conclusion, we have identified a new stress-induced gene which codes for a transmembrane protein that, when overexpressed, promotes formation of intracellular vacuoles followed by cell death. PMID- 11785948 TI - Vitamin D(3) augments osteoclastogenesis via vitamin D-responsive element of mouse RANKL gene promoter. AB - Receptor activator of NF-kappaB ligand (RANKL) is a membrane-bound signal transducer necessary for the induction and maintenance of osteoclasts. To clarify the molecular mechanism by which 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) augments osteoclasts, we characterized the promoter region of the mouse RANKL gene. Mirroring in vitro osteoclastogenesis demonstrated by a coculture of bone marrow macrophages with ST2 stromal cells, Northern blot, and nuclear run-on analyses showed that 1,25-(OH)(2)D(3) upregulate RANKL gene expression at the transcriptional level. Using a series of deletion mutants of mouse RANKL promoter luciferase reporter gene constructs, transient transfection studies revealed that the inductive effect of 1,25-(OH)(2)D(3) was abolished when the region up to -723 was deleted. An electrophoretic motility shift assay demonstrated that the VDR RXRbeta heterodimer bound to AGGTCAGCCTGGTTCA (-937/-922), and VDRE/nuclear protein supershift complexes that bound to anti-VDR and -RXRbeta antibodies were detected in the nuclear extract of 1,25-(OH)(2)D(3)-treated ST2 cells. Furthermore, induction of mutation to the putative VDRE also diminished the inductive effect of 1,25-(OH)(2)D(3). We therefore concluded that mouse RANKL gene is one of the target genes of 1,25-(OH)(2)D(3) containing a functional VDRE in the promoter region. PMID- 11785949 TI - Improvement of RNA aptamer activity against myasthenic autoantibodies by extended sequence selection. AB - Myasthenia gravis (MG) is mainly engendered by autoantibodies directed against acetylcholine receptors (AChRs) located in the postsynaptic muscle cell membrane. Previously, we isolated an RNA aptamer with 2'-amino pyrimidines using in vitro selection techniques that acted as a decoy against both a rat monoclonal antibody called mAb198, which recognizes the main immunogenic region on the AChR, and patient autoantibodies with MG (1). However, low affinity of this RNA to mAb198 relative to that of AChR might limit potential of the RNA as an inhibitor of the autoantibodies. To improve decoy activity of the RNA aptamer against autoantibodies, here we employed in vitro selection methods with RNA libraries containing extra random nucleotides extended to the 3' end of previously selected RNA sequences. RNAs isolated in this study showed significant increases in the binding affinities to mAb198 as well as bioactivities protecting AChRs on human cells from both mAb198 and patient autoantibodies, compared with the previous RNA aptamers. These results have important implications for the development of antigen-specific modulation of autoimmune diseases including MG. PMID- 11785950 TI - Cyclic AMP-specific phosphodiesterase 4 inhibitors promote ABCA1 expression and cholesterol efflux. AB - ATP cassette binding protein 1 (ABCA1) controls the apolipoprotein-mediated cholesterol efflux pathway and determines plasma HDL levels. Although cAMP is known to promote ABCA1 expression and cholesterol efflux from cells, it has not been determined whether cyclic nucleotide phosphodiesterase (PDE) isoforms regulate this pathway. We show that rolipram and cilomilast, inhibitors of cAMP specific PDE4, increase apolipoprotein A-I (apoA-I)-mediated cholesterol efflux up to 80 and 140% in human THP-1 and mouse J774.A1 macrophages, respectively, concomitant with an elevation of cAMP levels. The EC(50) value was estimated to be 1 to 2 microM for both inhibitors. Rolipram and cilomilast also increase ABCA1 protein expression in THP-1 and J774.A1 macrophages. Thus, PDE4 inhibitors cause parallel increases in cAMP levels, ABCA1 expression and apoA-I-mediated cholesterol efflux. PDE4 inhibitors may provide a novel strategy for the treatment of cardiovascular disease by mobilizing cholesterol from atherosclerotic lesions. PMID- 11785951 TI - Role of Ser530, Arg292, and His662 in the allosteric behavior of rabbit muscle phosphofructokinase. AB - Fructose-2,6-bisphosphate (Fru-2,6-P(2)) is a potent allosteric activator of the ATP-dependent phosphofructokinase (PFK) in eukaryotes. Based on the sequence homology between rabbit muscle PFK and two bacterial PFKs and the crystal structures of the latter, Ser(530), Arg(292) and His(662) of the rabbit enzyme are implicated as binding sites for Fru-2,6-P(2). We report here the effects of three mutations, S530D, R292A, and H662A on the activation of rabbit muscle PFK by Fru-2,6-P(2). At pH 7.0 and the inhibitory concentrations of ATP, the native enzyme gives a classic sigmoidal response to changes in Fru-6-P concentration in the absence of Fru-2,6-P(2) and a nearly hyperbolic response in the presence of the activator. Under the same conditions, no activation was seen for S530D. On the other hand, H662A can be activated but requires a 10-fold or higher concentration of Fru-2,6-P(2). Limited activation was observed for mutant R292A. A model illustrating the sites for recognition of Fru-2,6-P(2) in rabbit muscle PFK as well as the mechanism of allosteric activation is proposed. PMID- 11785952 TI - Saccharomyces cerevisiae Pra1p/Yip3p interacts with Yip1p and Rab proteins. AB - The regulation of membrane traffic involves the Rab family of Ras-related GTPases, of which there are a total of 11 members in the yeast Saccharomyces cerevisiae. Previous work has identified PRA1 as a dual prenylated Rab GTPase and VAMP2 interacting protein [Martinic et al. (1999) J. Biol. Chem. 272, 26991 26998]. In this study we demonstrate that the yeast counterpart of PRA1 interacts with Rab proteins and with Yip1p, a membrane protein of unknown function that has been reported to interact specifically with the Rab proteins Ypt1p and Ypt31p. Yeast Pra1p/Yip3p is a factor capable of biochemical interaction with a panel of different Rab proteins and does not show in vitro specificity for any particular Rab. The interactions between Pra1p/Yip3p and Rab proteins are dependent on the presence of the Rab protein C-terminal cysteines and require C-terminal prenylation. PMID- 11785953 TI - Truncated vitronectins: binding to immobilized fibrin and to fibrin clots, and their subsequent interaction with cells. AB - The plasminogen activator inhibitor-1 (PAI-1) is stabilized in its inhibitory conformation by binding to Vitronectin (Vn). The anchorage of PAI-1 to the fibrin fibers was recently shown to be mediated by Vn, and as such to modulate fibrinolysis. Here we report the mapping of the fibrin binding sites in Vn using truncated recombinant Vns, and show that two segments of Vn are involved: one at its carboxyl terminus (within residues 348-459) and one at its amino terminus (within residues 1-44). This mapping sets the stage for (i) the design of specific inhibitors for the Vn-fibrin interaction; (ii) for studying the role of this interaction in the anchoring of endothelial cells and platelets onto the fibrin clot; and (iii) for getting a deeper insight into the mechanism of the Vn fibrin interaction in fibrinolysis. (c)2002 Elsevier Science. PMID- 11785954 TI - Involvement of a Ca(2+)-dependent protein kinase component downstream to the gibberellin-binding phosphoprotein, RuBisCO activase, in rice. AB - Previously, we reported the identification of a gibberellin (GA)-binding protein in rice using ligand binding assay that was homologous to RuBisCO activase (Komatsu et al., FEBS Lett. 384, 167-171, 1996). Here, we provide an evidence for the involvement of protein kinases components downstream to the GA-binding phosphoprotein, RuBisCO activase in rice. Ca(2+)-dependent protein kinase activity was studied in subcellular fractions of leaf sheath from transgenic rice containing sense and antisense constructs of RuBisCO activase. In-gel kinase assay using histone III-S as a substrate showed constitutive induction of a 46- and 48-kDa Ca(2+)-dependent protein kinase activity in the sense transgenic plants. Kinase activities of these proteins were significantly reduced in the presence of uniconazole, a potent GA biosynthesis inhibitor, but one of them was strongly promoted by GA(3) treatment in transgenic plants carrying a smaller subunit of RuBisCO activase (OsrcaA1) compared to the larger subunit OsrcaA2. Also, in vitro phosphorylation studies using two-dimensional polyacrylamide gel showed changes in the degree of phosphorylation of several proteins in OsrcaA1- and OsrcaA2-sense transgenic rice. These studies suggest the presence of two independent cytosolic Ca(2+)-dependent protein kinase signaling components downstream to the GA-binding protein in rice suggesting their role in GA signaling. PMID- 11785956 TI - Differentiation of trophoblast lineage is associated with DNA methylation and demethylation. AB - Our previous study has shown that the placenta and kidney had different genomic methylation patterns regarding CpG island loci detected by restriction landmark genomic scanning (RLGS). To investigate whether differentiation involves changes in DNA methylation, we analyzed the rat Rcho-1 cell line, which retains trophoblast cell features and differentiates from stem cells into trophoblast giant cells in vitro. By RLGS, a total of 1,232 spots were identified in the Rcho 1 stem and differentiated giant cells. Four spots (0.3%) were detected only in giant cells, implying that the loci were originally methylated, but became demethylated during differentiation. Another four spots (0.3%) were detected only in stem cells, implying that these loci, originally unmethylated, became methylated during differentiation. DNAs from three loci that became methylated during differentiation were cloned and sequenced. All showed high homologies with expressed sequence tags (ESTs) or with genomic DNA of other species, suggesting that these loci are biologically important. Thus, the eight differentially methylated loci should be good tools to study epigenetic modification specific to differentiation of trophoblast giant cells. PMID- 11785955 TI - Expression of prostaglandin E(2) receptor subtypes in mouse hair follicles. AB - We investigated the mRNA distribution of the prostaglandin (PG) E(2) receptor subtypes and cyclooxygenases (COXs) in hair follicles of the mouse dorsal skin. In the 3-week hair follicles, which are in the anagen phase, EP3 and EP4 mRNA were expressed in the dermal papilla cells and the outer root sheath cells located in the hair bulb region, respectively. In the 8-week hair follicles, which are in the telogen phase, the signals for both EP3 and EP4 mRNAs had disappeared. To study the hair cycle-dependent expression of mRNAs for the EPs and COXs, an area of dorsal hair was depilated from 8-week-old mice. On days 8 and 12 after depilation, EP3 and EP4 mRNA were reexpressed in the dermal papilla cells and the outer root sheath cells, and the induction of COX-2 mRNA was also observed in the outer root sheath cells, the upper area of EP4 expression site. These results suggest that EP3 and EP4 receptors may involve in the development and regrowth of the hair follicles. PMID- 11785957 TI - PPARgamma is not a critical mediator of primary monocyte differentiation or foam cell formation. AB - In the present report we clarify the role of PPARgamma in differentiation and function of human-derived monocyte/macrophages in vitro. Rosiglitazone, a selective PPARgamma activator, had no effect on the kinetics of appearance of monocyte/macrophage differentiation markers or on cell size or granularity. Depletion of PPARgamma by more than 90% using antisense oligonucleotides did not influence accumulation of oxidized LDL or prevent the upregulation of CD36 that normally accompanies oxLDL treatment. In contrast, PPARgamma depletion reduced the expression of ABCA1 and LXRalpha mRNAs. Metalloproteinase-9 expression, a marker of atherosclerotic plaque vulnerability, was suppressed by rosiglitazone. We conclude that activation of PPARgamma does not affect monocyte/macrophage differentiation. In addition, PPARgamma is not absolutely required for oxLDL driven lipid accumulation, but is required for full expression of ABCA1 and LXRalpha. Our data support a role for rosiglitazone as a potential directly acting antiatherosclerotic agent. PMID- 11785958 TI - Expression and functional analyses of novel mutations of ATP-binding cassette transporter-1 in Japanese patients with high-density lipoprotein deficiency. AB - ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three different ABCA1 mutations associated with FHD (G1158A/A255T, C5946T/R1851X, and A5226G/N1611D) with respect to their expression in the passaged fibroblasts from the patients and in the cells transfected with the mutated cDNAs. Fibroblasts from the all patients showed markedly decreased cholesterol efflux to apolipoprotein (apo)-Al. In the fibroblasts homozygous for G1158A/A255T, the immunoreactive mass of ABCA1 could not be detected, even when stimulated by 9-cis-retinoic acid and 22-R hydroxycholesterol. In the fibroblasts homozygous for C5946T/R1851X, ABCA1 mRNA was comparable. Because the mutant ABCA1 protein (R1851X) was predicted to lack the epitope for the antibody used, we transfected FLAG-tagged truncated mutant (R1851X/ABCA1-FLAG) cDNA into Cos-7 cells, showing that the mutant protein expression was markedly reduced. The expression of N1611D ABCA1 protein was comparable in both fibroblasts and overexpressing cells, although cholesterol efflux from the cells was markedly reduced. These data indicated that, in the three patients investigated, the abnormalities and dysfunction of ABCA1 occurred at the different levels, providing important information about the expression, regulation, and function of ABCA1. PMID- 11785959 TI - Association of MR1 protein, an MHC class I-related molecule, with beta(2) microglobulin. AB - MR1 is a major histocompatibility complex (MHC) class I-related gene conserved among mammals, and its predicted amino acid sequence is relatively closer to the classical MHC class I molecules among several divergent class I molecules. However, as its molecular nature and function have not yet been clarified, we set out in this study to establish transfected P388 murine cell lines that stably produce a large number of MR1 proteins and conducted analyses to investigate the molecular nature of MR1. Immunoprecipitation and Western blot analyses with specific antisera revealed that the MR1 protein can associate with beta(2) microglobulin, suggesting its molecular form of a typical class I heterodimer composed of a heavy and a light chain (beta(2)-microglobulin), like the classical MHC class I molecules. PMID- 11785960 TI - Nek2 localizes to multiple sites in mitotic cells, suggesting its involvement in multiple cellular functions during the cell cycle. AB - Nek2 is a mammalian protein kinase that is structurally homologous to NIMA, a mitotic regulator in Aspergillus nidulans. To understand the possible cellular processes in which Nek2 participates during the cell cycle, we investigated the expression and subcellular localization of Nek2 in mitotic cells. The Nek2 protein levels were observed to be regulated in a cell cycle stage-specific manner in cultured cells. The cell cycle stage specificity of Nek2 expression was also confirmed in cells undergoing mitosis in vivo. Nek2 proteins were localized in both the nucleus and cytoplasm throughout the cell cycle, but exhibited dynamic changes in distribution, depending on the cell cycle stage. Nek2 was associated with chromosomes from prophase to metaphase and then was dissociated upon entering into anaphase. Nek2 then appeared at the midbody of the cytoplasmic bridge at telophase. Nek2 was also associated with the centrosome throughout the cell cycle as observed previously by others. Additionally, the nuclear localization of Nek2 was increased during S phase. Such dynamic behavior of Nek2 suggests that Nek2 may be a mitotic regulator that is involved in diverse cell cycle events. PMID- 11785961 TI - Retina dorsal/ventral patterning by Xenopus TBX3. AB - Although it is well known that patterning in the retina of vertebrates is essential for retina formation and for the retinotopic projection of axons in the embryo, knowledge of molecular and cellular mechanisms of retina patterning is limited. We have previously identified the Xenopus Tbx3 gene (XTbx3) which is expressed in the dorsal retina but not in the ventral retina in Xenopus embryos [H. Li, C. Tierney, L. Wen, J. Y. Wu, and Y. Rao (1997) Development 124, 603-615; M.-L. He, L. Wen, C. E. Campbell, J. Y. Wu, and Y. Rao (1999) Proc. Natl. Acad. Sci. USA 96, 10212-10217]. Dosage-sensitive phenotypes in humans suggest that the manipulation of the amount and location of its products could be informative for understanding its normal function. Here we report that ectopic expression of Tbx3 by mRNA injection suppressed formation of the ventral retina. Furthermore, Tbx3 injection led to inhibition of molecular markers for the ventral retina including Pax-2 and netrin, indicating that Tbx3 plays an important role in retina dorsal/ventral patterning in vertebrates by inhibition of gene expression for ventral retina specification. PMID- 11785962 TI - The C5 domain of Col6A3 is cleaved off from the Col6 fibrils immediately after secretion. AB - In articular cartilage, type VI collagen is concentrated in the pericellular matrix compartment. During protein synthesis and processing at least the alpha3(VI) chain undergoes significant posttranslational modification and cleavage. In this study, we investigated the processing of type VI collagen in articular cartilage. Immunostaining with a specific polyclonal antiserum against the C5 domain of alpha3(VI) showed strong cellular staining seen in nearly all chondrocytes of articular cartilage. Confocal laser-scanning microscopy and immunoelectron microscopy allowed localization of this staining mainly to the cytoplasm and the immediate pericellular matrix. Double-labeling experiments showed a narrow overlap of the C5 domain and the pericellular mature type VI collagen. Our results suggest that at least in human adult articular cartilage the C5 domain of alpha3(VI) collagen is synthesized and initially incorporated into the newly formed type VI collagen fibrils, but immediately after secretion is cut off and is not present in the mature pericellular type VI matrix of articular cartilage. PMID- 11785963 TI - Intact vinculin protein is required for control of cell shape, cell mechanics, and rac-dependent lamellipodia formation. AB - Studies were carried out using vinculin-deficient F9 embryonic carcinoma (gamma229) cells to analyze the relationship between structure and function within the focal adhesion protein vinculin, in the context of control of cell shape, cell mechanics, and movement. Atomic force microscopy studies revealed that transfection of the head (aa 1-821) or tail (aa 811-1066) domain of vinculin, alone or together, was unable to fully reverse the decrease in cell stiffness, spreading, and lamellipodia formation caused by vinculin deficiency. In contrast, replacement with intact vinculin completely restored normal cell mechanics and spreading regardless of whether its tyrosine phosphorylation site was deleted. Constitutively active rac also only induced extension of lamellipodia when microinjected into cells that expressed intact vinculin protein. These data indicate that vinculin's ability to physically couple integrins to the cytoskeleton, to mechanically stabilize cell shape, and to support rac-dependent lamellipodia formation all appear to depend on its intact three-dimensional structure. PMID- 11785964 TI - A novel member of the leucine-rich repeat superfamily induced in rat astrocytes by beta-amyloid. AB - beta-Amyloid (Abeta) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which Abeta contributes to the progression of neuropathologic changes have not been established entirely, there is little doubt that the association of Abeta with astrocytes, the predominant cell type in brain, has significant influence on exacerbation of the disease. In an effort to identify key molecules involved in AD, we investigated Abeta-responsive genes using rat astrocytes. In this study, we identified a novel Abeta-induced rat gene, designated as Lib, encoding a type I transmembrane protein with an extracellular domain that contains fifteen leucine-rich repeats (LRRs). Human counterpart of rat Lib is located on chromosome 3q29 and human Lib mRNA found in particularly placenta. Lib mRNA levels in rat C6 astrocytoma cells can be increased by pro-inflammatory cytokines and the rat Lib-transfected cells express Lib protein on the cell surfaces. Lib appears to be a member of the LRR superfamily which is involved in cell-cell and/or -extracellular matrix interactions including adhesion or target recognition in neuroinflammatory states. PMID- 11785965 TI - Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. AB - Articular cartilage exhibits little intrinsic repair capacity, and new tissue engineering approaches are being developed to promote cartilage regeneration using cellular therapies. The goal of this study was to examine the chondrogenic potential of adipose tissue-derived stromal cells. Stromal cells were isolated from human subcutaneous adipose tissue obtained by liposuction and were expanded and grown in vitro with or without chondrogenic media in alginate culture. Adipose-derived stromal cells abundantly synthesized cartilage matrix molecules including collagen type II, VI, and chondroitin 4-sulfate. Alginate cell constructs grown in chondrogenic media for 2 weeks in vitro were then implanted subcutaneously in nude mice for 4 and 12 weeks. Immunohistochemical analysis of these samples showed significant production of cartilage matrix molecules. These findings document the ability of adipose tissue-derived stromal cells to produce characteristic cartilage matrix molecules in both in vitro and in vivo models, and suggest the potential of these cells in cartilage tissue engineering. PMID- 11785966 TI - Molecular cloning and characterization of pentachlorophenol-degrading monooxygenase genes of Pseudomonas sp. from the chemostat. AB - Pseudomonas sp. strain IST 103 (PCP103) capable of utilizing pentachlorophenol (PCP) was determined by utilization of a carbon source and release of the hydroxylating enzyme PCP-4 monooxygenase. The metabolites were extracted from the culture medium and analyzed by high-performance liquid chromatography. The enzyme purified to apparent homogeneity from an extract of PCP-grown cells indicated that a fraction of DEAE-cellulose ion exchange chromatography of molecular size of 30,000 kDa determined by gel filtration chromatography and SDS-polyacrylamide gel electrophoresis was responsible for dechlorination of PCP. The plasmid isolated from the bacterium was subjected to Shotgun cloning by restriction digestion by BamHI, HindIII, and SalI, ligated to pUC19 vector, and transformed into Escherichia coli XLBlue1alpha. The recombinant clones having higher potentiality to degrade PCP were selected by utilization of a carbon source and release of intermediary metabolites during degradation of PCP as the sole source of carbon and energy. The recombinant clones, which contained an insert of 3.0 kb of SalI and HindIII sites, were sequenced and compared with gene sequences deposited in GenBank by BLAST search; this indicated homology with the thdf gene of monooxygenase of thiophene and furan. Southern blot analysis performed by developing gene probes indicated the presence of the PCP monooxygenase gene in plasmids of the bacterium. PMID- 11785967 TI - Modification of histidine (B10) is the causative agent for a superactive form of insulin. AB - The site of modification that is responsible for the formation of superactive insulin (ILM) was determined. The insulin derivative was prepared by treatment of insulin-Sepharose with ammonium bicarbonate. It was found that the insulin was bound to the resin through histidine B10, His (B10), and its ammonium bicarbonate mediated release resulted in an insulin analog in which His (B10) was modified on the imidazole ring. This modification was reversible upon storage, resulting in normal levels of insulin activity. Amino acid analysis of a peptide containing this modified histidine revealed some aspartic acid. Since Asp (B10) insulin is also superactive, the observed superactivity may thus stem from either modification of the histidine or its conversion to aspartic acid. PMID- 11785968 TI - Double base lesions of DNA by a metabolite of carcinogenic benzo[a]pyrene. AB - Carcinogenic benzo[a]pyrene (BP) is generally considered to show genotoxicity by forming DNA adducts of its metabolite, BP-7,8-diol-9,10-epoxide. We investigated oxidative DNA damage and its sequence specificity induced by BP-7,8-dione, another metabolite of BP, using (32)P-5'-end-labeled DNA. Formamidopyrimidine-DNA glycosylase treatment induced cleavage sites mainly at G residues of 5'-TG-3' sequence and at poly(C) sequences, in DNA incubated with BP-7,8-dione in the presence of NADH and Cu(II), whereas piperidine treatment induced cleavage sites at T mainly of 5'-TG-3'. BP-7,8-dione strongly damaged the G and C of the ACG sequence complementary to codon 273 of the p53 gene. Catalase and a Cu(I) specific chelator attenuated the DNA damage, indicating the involvement of H(2)O(2) and Cu(I). BP-7,8-dione with NADH and Cu(II) also increased 8-oxo-7,8 dihydro-2'-deoxyguanosine formation. We conclude that oxidative DNA damage, especially double base lesions, may participate in the expression of carcinogenicity of BP in addition to DNA adduct formation. PMID- 11785969 TI - Molecular cloning and functional characterization of mouse coactosin-like protein. AB - Coactosin was first isolated from Dictyostelium discoideum and, as reported, human coactosin-like protein (CLP) was identified in a yeast two-hybrid screen using 5-lipoxygenase (5LO) as a bait. A mouse CLP (mCLP) cDNA clone was identified among EMBL/GenBank EST sequences. The derived amino acid sequence (142 residues) was 95.1% identical with human CLP. Here, we also show that mCLP interacts with actin and 5LO in the two-hybrid system. High-speed cosedimentation assays and GST-binding assays confirmed these protein interactions. In chemical cross-linking experiments, one molecule of mCLP was covalently linked to either one subunit of actin or one molecule of 5LO. The mCLP-F-actin and mCLP-5LO associations were pH-insensitive and Ca(2+)-independent. However, association with actin was best observed at low salt concentrations, while association with 5LO was favored by salt, indicating different binding characteristics. PMID- 11785970 TI - Increased activity of c-Src and Csk in fibroblasts transformed by v-src oncogene. AB - When c-Src and v-Src were immunoprecipitated together from hamster fibroblasts transformed by Rous sarcoma virus containing v-src oncogene, the total Src activity was almost threefold higher compared to c-Src activity in the control cells. The activity of v-Src immunoprecipitated separately, however, accounting for only 40% of the total Src activity, indicating that c-Src is activated upon transformation. An increased activity of Csk was also found in RSV-transformed cells. It decreased upon serum stimulation in parallel with an increase in Src kinase activity. In nontransformed cells, serum stimulation induced an enhanced Csk activity, but no changes in c-Src activity were observed. This may suggest that Csk may have more functions in hamster fibroblasts, in addition to its inhibitory effect on c-Src. PMID- 11785971 TI - Roles of DNA fragmentation factor and poly(ADP-ribose) polymerase-1 in sensitization of fibroblasts to tumor necrosis factor-induced apoptosis. AB - DNA fragmentation factor (DFF) comprises DFF45 and DFF40 subunits, the former of which acts as an inhibitor of the latter (the catalytic subunit) and whose cleavage by caspase-3 results in DFF activation. Disruption of the DFF45 gene blocks the generation of 50-kb DNA fragments and confers resistance to apoptosis. We recently suggested that the early fragmentation of DNA by DFF and the consequent activation of poly(ADP-ribose) polymerase-1 (PARP-1), mitochondrial dysfunction, and activation of caspase-3 contribute to an amplification loop in the apoptotic process. To verify the existence of such a loop, we have now examined the effects of restoring DFF expression in DFF45-deficient fibroblasts. Co-transfection of mouse DFF45(-/-) fibroblasts with plasmids encoding human DFF40 and DFF45 reversed the apoptosis resistance normally observed in these cells. The DFF45(-/-) cells regained the ability to fragment their DNA into 50-kb pieces in response to TNF, which resulted in a marked activation of PARP-1 and a concomitant depletion of intracellular NAD. DFF expression also resulted in an increase both in cytochrome c release into the cytosol and in caspase-3 activation triggered by TNF. These results support the importance of DFF, PARP-1, mitochondria, and caspase-3 in an amplification phase of TNF-induced apoptosis. PMID- 11785972 TI - Iminodiacetate and nitrilotriacetate degradation by Kluyveromyces marxianus IMB3. AB - The thermotolerant yeast Kluyveromyces marxianus IMB3 was capable of utilising either iminodiacetate or nitrilotriacetate as a sole source of nitrogen for growth. Cell extracts contained iminodiacetate dehydrogenase and nitrilotriacetate monooxygenase activities, suggesting the presence in the yeast of orthologues of these bacterial enzymes. The activities were not detectable in complete medium-growth cells, nor in nitrogen-starved cells, suggesting an inducible biodedgradation pathway for biodegradation of these xenobiotics, which has not been previously reported in a eukaryotic cell system. This observation emphasises the hitherto unrealised importance of yeast strains in the biodegradation of xenobiotics in the environment. PMID- 11785973 TI - Bacillus subtilis inorganic pyrophosphatase: the C-terminal signature sequence is essential for enzyme activity and conformational integrity. AB - Bacillus subtilis inorganic pyrophosphatase is the first member of a newly identified Family II of PPases. To examine the role of a signature sequence found near the C-terminus, two truncated variants and a series of site-specific mutants were produced. A truncation of 17 residues (17AATR) but also single alanine substitutions, R295A and K296A, produced inactive enzyme. Removal of 5 nonconserved terminal residues (5AATR) markedly affected enzyme stability. Replacing S294 with A, T, C, or V decreased activity, the latter two mutations showing the greatest effect. Substitutions V299I and V300I had no or minor effects, whereas V300W and V299G/V300W significantly reduced activity. The sizes of truncated proteins and the full-length PPase were indistinguishable by gel filtration. We conclude that the C-terminus has no role in multimerization, while both its conserved and nonconserved regions are essential for full enzyme activity. The signature sequence is required for both the conformation and composition of the active site. PMID- 11785974 TI - A new antifungal protein and a chitinase with prominent macrophage-stimulating activity from seeds of Phaseolus vulgaris cv. pinto. AB - From the seeds of the pinto bean (Phaseolus vulgaris cv. pinto), a chitinase and a novel antifungal protein, both with the ability of markedly augmenting nitrite production by murine peritoneal macrophages, were isolated. The antifungal proteins, designated phasein A and phasein B, exhibited molecular weights of 28 and 32 kDa, respectively. Phaseins A and B were adsorbed on Affi-gel blue gel and CM-Sepharose and were eluted as adjacent peaks from CM-Sepharose. Phasein A demonstrated potent antifungal activity toward Fusarium oxysporum and Physalospora piricola. Phasein B was more potent than phasein A toward P. piricola but less potent than phasein A toward F. oxysporum and Rhizoctonia solani. Both antifungal proteins inhibited the activity of HIV-1 reverse transcriptase and translation in a rabbit reticulocyte lysate system, with phasein B being more potent. Nitrite production by mouse macrophages was greatly boosted in the presence of both phaseins A and B, although the effect of phasein A was more prominent. The bioactivities of phaseins were in general potent compared with those of other antifungal proteins. PMID- 11785975 TI - Poly-L-lysine/heparin stimulates angiogenesis in chick embryo chorioallantoic membrane. AB - The effects of heparin on angiogenesis are controversial, with some studies claiming stimulatory and other studies claiming inhibitory effects. Since heparin in human plasma is complexed with basic peptides and proteins, we studied the angiogenic effect of complexes resulting by mixing poly-L-lysine (a basic heparin binding polypeptide) and heparin. Angiogenesis was investigate by chorioallantoic membrane assay. In specimens treated with PBS (negative control), or poly-L lysine, no significant vascular reaction was detectable. Heparin induced only moderate angiogenic response. However, neutral complexes purified from a mixture of poly-L-lysine and heparin (20/1, w/w) induced a very strong angiogenic response. These results demonstrate that the angiogenic effect of heparin was associated with neutralization of electric charge when the polysaccharide was complexed with a basic peptide. PMID- 11785976 TI - Transport of L-Lactate, D-Lactate, and glycolate by the LldP and GlcA membrane carriers of Escherichia coli. AB - To examine the substrate specificity of the membrane transport carriers LldP (L lactate permease) and GlcA (glycolate permease) of Escherichia coli, a mutant strain lacking their structural genes and blocked in the metabolism of the tested substrates was constructed and transformed with a plasmid bearing either the lldP or the glcA gene. Each transformant acquired the ability to accumulate L-lactate, D-lactate, and glycolate against a high concentration gradient. Substrate accumulation was inhibited by carbonyl cyanide m-chlorophenylhydrazone, a hydrophobic proton conductor that dissipates proton motive force. Competition of (14)C-L-lactate transport by nonradioactive L-lactate, D-lactate, and glycolate in LldP synthesizing cells and competition of (14)C-glycolate transport by the same three substrates in GlcA synthesizing cells showed that both carriers effectively transported all three substrates with a K(i) value ranging from 10 to 20 microM. D-Lactate does not appear to have a permease of its own. Utilization of the compound depends mainly on LldP. PMID- 11785978 TI - Glycemic control in mice with targeted disruption of the glucagon receptor gene. AB - The action of glucagon in the liver is mediated by G-coupled receptors. To examine the role of glucagon in glucose homeostasis, we have generated mice in which the glucagon receptor was inactivated (GR(-/-) mice). Blood glucose levels were somewhat reduced in GR(-/-) mice relative to wild type, in both the fed and fasted state. Plasma insulin levels were not significantly affected. There was no significant effect on fasting plasma cholesterol or triglyceride levels associated with deletion of the glucagon receptor. Glucose tolerance, as assessed by an oral glucose tolerance test, improved. Plasma glucagon levels were strikingly elevated in both fed and fasted animals. Despite a total absence of glucagon receptors, these animals maintained near-normal glycemia and normal lipidemia, in the presence of circulating glucagon concentrations that were elevated by two orders of magnitude. PMID- 11785977 TI - Serological cloning of PARIS-1: a new TBC domain-containing, immunogenic tumor antigen from a prostate cancer cell line. AB - Identifying immunogenic tumor antigens plays a critical role in developing efficient diagnostic and therapeutic strategies for treatment of cancer. Using a recently developed technology, serological identification of antigens by recombinant expression cloning (SEREX), we identified a total of 8 genes whose expression elicited antibody responses in prostate cancer patients. Of the 8 genes, 5 represented known genes in the GenBank database, 2 were previously uncharacterized genes, and 1 showed sequence homology to a mouse gene. The sequence feature and the expression of one of the novel genes, prostate antigen recognized and identified by SEREX (PARIS-1), are determined in this study. The PARIS-1 cDNA is 3257 bp in length and contains a complete open reading frame of 2751 bp encoding for a primary translation product of 917 amino acids. Using Northern blot hybridization assay, we detected a single species of approximately 3.3 kb PARIS-1 mRNA that is differentially expressed in prostate normal and cancer cells. Western blot analysis confirmed the expression of the PARIS-1 protein in these cells. Structure analysis revealed that PARIS-1 protein contains a TBC domain that is conserved in the family of cell cycle-regulatory and Rab GTPase-activating proteins (Rab-GAP). Thus, the PARIS-1 protein may play a role in regulation of cell differentiation and growth or represent a new member of the Rab-GAP family. PMID- 11785980 TI - Identification of a region critical for proteolysis of the human growth hormone receptor. AB - Release of soluble growth hormone binding protein (GHBP) corresponding to the extracellular domain of the GH receptor (GHR) occurs via distinct mechanisms depending on species. In human, proteolysis of full length GHR results in liberation of GHBP into the extracellular medium. A putative protease responsive for GHR cleavage has been identified, however, the residues involved are still unknown. In this study, using the mutational approach to the extracellular domain of the human GHR, we demonstrated that deletion of three residues located close to the transmembrane domain abolishes constitutive GHBP shedding without change in cellular GH binding. Deletion also significantly decreased the phorbol 12 myristate 13-acetate (PMA)-induced release of GHBP and the accumulation of membrane-anchored remnant proteins. Taken together, these results suggest that integrity of the juxtamembrane region of GHR is necessary for its biochemical cleavage and that a common mechanism is involved in constitutive and PMA-induced shedding. PMID- 11785979 TI - Ligand-dependent activation of the melanocortin 5 receptor: cAMP production and ryanodine receptor-dependent elevations of [Ca(2+)](I). AB - The melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands. The purpose of this study was to identify the peptide that functions as a natural ligand at the MC5R in the skin. alpha-MSH, ACTH1-39, ACTH1-17, ACTH1-10, and ACTH4-10 all increased the production of cAMP in HEK293 cells transfected with the mouse MC5R. alpha-MSH and ACTH1-17 were the most potent in this respect. In addition, all peptides stimulated a rapid and transient increase in [Ca(2+)](i), and, ACTH1-10 was the most potent. The increases in [Ca(2+)](i) were of intracellular origin, but not associated with inositol phosphate production. The elevations in [Ca(2+)](i) were reduced by ruthenium red and procaine and it is therefore possible that they were mediated via ryanodine receptors. PMID- 11785981 TI - HSP90, HSP70, and GAPDH directly interact with the cytoplasmic domain of macrophage scavenger receptors. AB - The macrophage scavenger receptor (MSR) is a trimeric membrane protein which binds to modified low-density lipoprotein (LDL) and has been indicated in the development of atherosclerosis. It has recently been demonstrated that the N terminal cytoplasmic domain of MSR has an important role in the efficient internalization and cell-surface expression of the receptor. This study shows that the N-terminal cytoplasmic domain in bovine was constructed using a peptide architecture technique in which the peptide chain was bundled at their C-terminus to yield a trimeric form and that this did not form an ordered structure. Furthermore, the binding proteins to the cytoplasmic domain of MSR were determined for the first time using a peptide affinity column. Sequence analyses of the specific binding proteins in bovine revealed that heat shock protein 90 (HSP90), heat shock protein 70 (HSP70), leucine aminopeptidase (LAP), adenocylhomocysteinase, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were included. GST-pull-down assay and immunoprecipitation analyses on HSP90, HSP70, and GAPDH showed that all these proteins could bind to the cytoplasmic domain of MSR in vitro and in vivo. These proteins interact with the cytoplasmic domain directly and may have an effect on the functions of MSR such as internalization, cell-surface expression, and signal transduction. PMID- 11785982 TI - Isolation and characterization of mouse homolog of the neutrophil activating peptide-2. AB - In the presence of thrombopoietin (TPO), megakaryocytes mature by polyploidization and cytoplasmic maturation, and the matured megakaryocytes induce drastic morphological change and proplatelet formation and release a number of platelets. However, the regulatory mechanism of this unique differentiation process is still obscure. We therefore attempted to identify the factors, expression of which is induced by TPO stimulation in mouse bone marrow megakaryocytes. We isolated the mouse homolog of the neutrophil activating peptide-2 (NAP-2). Mouse NAP-2 cDNA encodes a predicted sequence of 113 amino acids and contains the Cys motif (CXC) found in other members of the alpha chemokine family. At the amino acid level, the predicted mouse NAP-2 has 50.4%, 51.8%, and 72.6% identity with the predicted human, pig, and rat NAP-2, respectively. Northern blot analysis demonstrates that mouse NAP-2 is expressed only in spleen. Furthermore, the RT-PCR technique shows that the mouse NAP-2 gene is clearly upregulated by TPO stimulation in mouse megakaryocytes. PMID- 11785983 TI - Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. AB - We and others have recently shown that the major molecular target of nitrogen containing bisphosphonate drugs is farnesyl diphosphate synthase, an enzyme in the mevalonate pathway. In an in vitro screen, we discovered a bisphosphonate, NE21650, that potently inhibited farnesyl diphosphate synthase but, unlike other N-BPs investigated, was also a weak inhibitor of isopentenyl diphosphate isomerase. NE21650 was a more potent inhibitor of protein prenylation in osteoclasts and macrophages, and a more potent inhibitor of bone resorption in vitro, than alendronate, despite very similar IC(50) values for inhibition of farnesyl diphosphate synthase. Our observations show that minor changes to the structure of bisphosphonates allow inhibition of more than one enzyme in the mevalonate pathway and suggest that loss of protein prenylation due to inhibition of more than one enzyme in the mevalonate pathway may lead to an increase in antiresorptive potency compared to bisphosphonates that only inhibit farnesyl diphosphate synthase. PMID- 11785984 TI - Inverse relationship of skeletal muscle glycogen from wild-type and genetically modified mice to their phosphorylase a activity. AB - Leg muscle was biopsied and frozen for storage at -70 degrees C. from 5 wild-type mice, two knocked out acid alpha-glucosidase (GAA) gene mice, and seven glycogen synthase plus glucose muscle transporter transgenic mice. All of the wild-type mice had very little muscle glycogen (3.58 +/- 1.67 micromols glucosyl subunits per g muscle), and 52% or more of its glycogen phosphorylase activity without AMP (69% +/- 17% glycogen phosphorylase a). In contrast the GAA knockout and transgenic mice had glycogen ranging from 63 to 297 micromols glucosyl subunits per g muscle, and very little or no glycogen phosphorylase activity without 1.00 mM AMP (4.8% and less glycogen phosphorylase a). This suggests that there is an inverse relationship between mouse muscle phosphorylase a and the muscle's glycogen content. PMID- 11785985 TI - A critical role for the carboxy terminal region of the proprotein convertase, PACE4A, in the regulation of its autocatalytic activation coupled with secretion. AB - PACE4A is a member of the mammalian subtilisin-like proprotein convertase family which is responsible for the proteolytic activation of precursors into their biologically active forms. Previously we reported that the maturation of proPACE4A occurs via a intramolecular autoactivation and cleavage of the propeptide is a rate-limiting step for the secretion of PACE4A (Nagahama et al., FEBS Lett. (1998) 434, 155-159). Although PACE4A is a putative secretory enzyme, it matures and is secreted much slower than general secretory proteins. In this study, we investigated the molecular mechanism underlying this slow maturation. The deletion of 25 amino acids at the carboxy terminus is sufficient for a marked acceleration in both the maturation and secretion of PACE4A. The carboxyl truncated proPACE4A existed only as a monomer-sized form in the endoplasmic reticulum, whereas the wild type of proPACE4A existed in larger forms. Further, the fusion construct of yellow fluorescent protein and the carboxy-terminal sequence of PACE4A associated with the proPACE4A moiety and inhibited maturation. Thus the carboxy terminus of PACE4A functions as a potent autoinhibitor of its activation, resulting in the retention of proPACE4A in the endoplasmic reticulum. These findings indicate that PACE4A activity is highly controlled by a unique system at post-translational level. PMID- 11785986 TI - r-Hirudin for percutaneous coronary interventions--time to reconsider? PMID- 11785987 TI - Stent thrombosis: "(ultra)sound the warning". PMID- 11785988 TI - The meaning of suboptimal coronary flow reserve after coronary balloon angioplasty. PMID- 11785989 TI - Modern management of heart failure: education as well as medication. PMID- 11785990 TI - The heart in thalassaemia. PMID- 11785991 TI - Properly defining white coat hypertension. PMID- 11785992 TI - Why model coronary heart disease? PMID- 11785993 TI - Efficacy of hirudin in reducing cardiovascular events in patients with acute coronary syndrome undergoing early percutaneous coronary intervention. AB - AIMS: Although hirudin is superior to unfractionated heparin for prevention of death, myocardial infarction, or refractory ischaemia in patients with non-ST elevation acute coronary syndrome, it is not clear whether hirudin is also of benefit in acute coronary syndrome patients undergoing early percutaneous coronary intervention. METHODS AND RESULTS: In the OASIS 2 trial, 10 141 patients with non-ST-elevation acute coronary syndrome were randomized to 72 h of intravenous hirudin or unfractionated heparin. Percutaneous coronary intervention was performed at the discretion of the investigator. One hundred and seventeen patients underwent percutaneous coronary intervention within the first 72 h ("early percutaneous coronary intervention"). In patients undergoing early percutaneous coronary intervention, hirudin compared with unfractionated heparin was associated with a significantly lower incidence of death or myocardial infarction at 96 h (6.4% vs 21.4%, OR 0.30; 95% CI: 0.10-0.88) and 35 days (6.4% vs 22.9%, OR 0.25; 95% CI: 0.07-0.86). In the unfractionated heparin group, death or myocardial infarction was significantly higher at 35 days in patients undergoing early percutaneous coronary intervention compared with those managed conservatively (22.9% vs 7.3%, OR 3.14, P<0.001) but this early percutaneous coronary intervention-related hazard was not observed in hirudin-treated patients (6.4% vs 6.8%, OR 0.94 P=1.0). A time-dependent covariate for percutaneous coronary intervention was not significant in a Cox regression model, suggesting a similar treatment benefit with hirudin before and after percutaneous coronary intervention. After adjustment for percutaneous coronary intervention propensity, the benefits of hirudin remained significant. There were three major bleeds in patients undergoing early percutaneous coronary intervention, all in patients randomized to hirudin. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome undergoing early percutaneous coronary intervention, a direct thrombin inhibitor such as hirudin may be more effective than heparin in reducing the incidence of ischaemic complications. PMID- 11785994 TI - Predictors and outcomes of stent thrombosis: an intravascular ultrasound registry. AB - AIMS: To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance. METHODS AND RESULTS: A total of 53 patients were enrolled (mean age 61+/-9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1.6+/-0.8 stents/artery with 87% undergoing high-pressure dilatation (> or =14 atmospheres). The minimum stent area was 7.7+/-2.8 mm(2)with a mean stent expansion of 81.5+/-21.9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30.0, P<0.001). Stent thrombosis occurred at 132+/-125 h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%. CONCLUSION: On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment. PMID- 11785995 TI - Flow velocity and predictors of a suboptimal coronary flow velocity reserve after coronary balloon angioplasty. AB - AIMS: This study was conducted to analyse flow velocity parameters and predictors of a suboptimal coronary flow reserve (<2.5) following balloon angioplasty. METHODS: Two hundred and twenty-five patients underwent sequential intracoronary Doppler as part of the DEBATE I study. Of these, 183, with complete angiography and Doppler at the 6-month follow-up, were included. Univariate and multivariate logistic analysis was performed to identify independent predictors of post procedural suboptimal coronary flow reserve, defined as coronary flow reserve <2.5. RESULTS: Forty-eight per cent (n=88) of the patients achieved a suboptimal coronary flow reserve. These patients had higher baseline velocities (cm.s(-1)) before balloon angioplasty (18+/-9 vs 14+/-6, P=0.004), after balloon angioplasty (22+/-11 vs 14+/-5, P<0.001) and at follow-up (19+/-9 vs 16+/-6, P=0.011) than the optimal coronary flow reserve group. Although the suboptimal group had lower hyperaemic velocities (cm.s(-1)) after balloon angioplasty than the optimal group (42+/-17 vs 49+/-16, P=0.008), these velocities became similar at follow-up. Increasing age (odds ratio, OR 1.071, P=0.0002), female gender (OR 2.52, P=0.014) and increasing pre-procedural baseline average peak velocities (OR 1.056, P<0.001) were found to be independent predictors of a suboptimal coronary flow reserve following balloon angioplasty. CONCLUSION: A suboptimal coronary flow reserve was associated with (1) a chronically elevated baseline average peak velocity (2) a transient deficit in the hyperaemic average peak velocity (3) the elderly, and female gender. PMID- 11785996 TI - Randomized, controlled trial of integrated heart failure management: The Auckland Heart Failure Management Study. AB - AIMS: To determine the effect of an integrated heart failure management programme, involving patient and family, primary and secondary care, on quality of life and death or hospital readmissions in patients with chronic heart failure. METHODS AND RESULTS: This trial was a cluster randomized, controlled trial of integrated primary/secondary care compared with usual care for patients with heart failure. The intervention involved clinical review at a hospital-based heart failure clinic early after discharge, individual and group education sessions, a personal diary to record medication and body weight, information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic. Follow-up was for 12 months. One hundred and ninety-seven patients admitted to Auckland Hospital with an episode of heart failure were enrolled in the study. There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission. The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group (-11.1 vs -5.8 respectively, 2 P=0.015). The main effect of the intervention was attributable to the prevention of multiple admissions (56 intervention group vs 95 control group, 2 P=0.015) and associated reduction in bed days. CONCLUSIONS: This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days. PMID- 11785997 TI - Right ventricular cardiomyopathy in beta-thalassaemia major. AB - AIMS: To evaluate right ventricular function in patients with beta-thalassaemia major and congestive heart failure. Background In patients with beta-thalassaemia major a high incidence of cardiac involvement still exists despite improved prognosis with chelation therapy. Development of severe right heart failure is common and has been attributed to pulmonary hypertension secondary to lung haemochromatosis. However, the possibility of direct right ventricular myocardial involvement in the absence of significant pulmonary hypertension has not been adequately investigated. METHODS: Twenty-nine consecutively screened patients with beta-thalassaemia major and congestive heart failure were investigated by Doppler echocardiography, right ventricular first-pass radionuclide examination and cardiac catheterization. Haemodynamic data were obtained both before and after volume loading. A control group of 39 patients with beta-thalassaemia major, free from cardiac disease, and matched for age, gender, body surface area and heart rate was used for comparison. A subset of the control thalassaemic group (n=15) underwent both radionuclide and haemodynamic assessment. RESULTS: The majority of patients were on non-optimal chelation therapy. Only two of 29 patients were found to have cor pulmonale. One other patient suffered from constrictive pericarditis. A restrictive filling pattern in both ventricles and left ventricular systolic dysfunction were evident in the other 26 patients. Pulmonary artery pressure (systolic, 33+/-8 vs 27+/-5 mmHg, P<0.05) and pulmonary vascular resistance (114+/-56 vs 65+/-29 dynes. s. cm(-5), P<0.01) were only mildly elevated in the heart failure group. After volume challenge, cardiac output remained unchanged although the increments of ventricular filling pressures were significant (Deltaright atrial: 4.8+/-2.2 mmHg, P<0.05; Deltapulmonary capillary wedge: 5.6+/-2.9 mmHg, P<0.05) and correlated with each other (r=0.69;P<0.001) in heart failure patients, suggesting pericardial constraint and ventricular interaction. In these patients compared with the control thalassaemic group, a lower right ventricular ejection fraction (29%+/-9 vs 59%+/-6, P<0.0001) without correlation with pulmonary artery pressures was found. Haemodynamically significant right ventricular dysfunction defined as mean right atrial pressure >10 mmHg and ratio of mean right atrial-to-capillary wedge pressure >0.8 was evident in 15 of the 26 patients (58%), all with severe symptoms, representing three fourths of the patients in functional class III and IV. Simultaneous pressure recordings in six of these 15 patients showed equalization of ventricular end-diastolic pressures within 5 mmHg. CONCLUSION: The majority of patients with beta-thalassaemia major and severe congestive heart failure demonstrated a unique haemodynamic pattern similar to that described in predominant right ventricular infarction, indicating severe right ventricular cardiomyopathy in addition to left ventricular dysfunction. The incidence of cor pulmonale as a cause of right heart failure seems to be much lower than previously hypothesized. PMID- 11785998 TI - Heart rate variability as a predictor of mortality in patients with AA and AL amyloidosis. AB - AIMS: Patients with AA and AL amyloidosis have a limited life-expectancy. The aim of this study was to investigate whether heart rate variability can predict mortality in these patients. METHODS AND RESULTS: Twenty-two recently diagnosed patients with AA and 23 patients with AL amyloidosis were included. Fifteen patients (5 AA, 10 AL) died within 1 year. Twenty-four hour Holter recording was performed to quantify the mean of all normal to normal RR-intervals (mean NN) and the standard deviation of all normal to normal RR-intervals (SDNN). The SDNN predicted 1-year mortality in the total group of patients with amyloidosis. The median SDNN was 73 ms. In patients with an SDNN < or =73 ms, the risk of dying within 1 year was found to have increased 3.5-fold (P=0.0036; 95% CI 1.1-11.0). An SDNN < or =50 ms, a predictor of mortality in other patient groups, increased the risk of dying within 1 year 22-fold (P=0.0001; 95% CI 5.4-90.4). In contrast to patients with AA amyloidosis, in the subgroup analysis of patients with AL amyloidosis the SDNN remained a predictive parameter (SDNN < or =50 ms: risk ratio 11.5, 95% CI 2.4-56.2, P=0.0025). CONCLUSION: The SDNN is a strong predictor of short-term mortality in patients with AL amyloidosis. PMID- 11785999 TI - Tissue Doppler analysis of age-dependency in diastolic ventricular behaviour and filling: a cross-sectional study of healthy hearts (the Umea General Population Heart Study). AB - BACKGROUND: Much in the diagnosis of diastolic ventricular dysfunction is dependent upon the filling pattern, and most patients diagnosed with diastolic heart failure are elderly. Data from healthy asymptomatic individuals across a range of ages are rare. We sought to find an age-related variation in normal diastolic physiology, specifically the filling pattern and segmental myocardial longitudinal velocities. METHODS AND RESULTS: To assess the effect of normal ageing on left ventricular longitudinal function, we studied myocardial shortening and lengthening velocities using the tissue Doppler technique in 60 healthy subjects who were randomly selected from the Umea (Sweden) General Population Register, which represents a wide range of ages (23-88 years). Myocardial velocities were documented at four left ventricular sites (anterior, left, posterior and septal) and at three levels (basal, mid-cavity and apical). Transmitral, transtricuspid and pulmonary venous flow velocities were recorded using pulsed-wave Doppler. While systolic myocardial velocities were conserved across ages, there was a marked decrease in early diastolic velocities with age (from 16 cm. s(-1)at 30 years to 9 cm. s(-1)at 80 years at the basal segment) and a corresponding significant increase in late diastolic velocities (from 10 to 16 cm. s(-1)). Although these findings were most marked at the basal level, they were also clearly manifested at the apical level. Myocardial lengthening velocities were related to transmitral flow velocities, showing a correlation of 0.64 (P<0.0001) in early diastole and 0.68 (P<0.0001) in late diastole. Finally, diastolic pulmonary venous flow velocity was found to correlate with early diastolic myocardial velocities (at the basal level, r=0.53, P<0.0001). CONCLUSIONS: Normal ageing causes a decrease in early diastolic and a substantial increase in late diastolic myocardial lengthening velocities. These changes explain the known trends in the transmitral flow pattern with age. In contrast, systolic myocardial velocities do not change significantly with age. These findings should be considered when evaluating diastolic function, especially in the elderly. PMID- 11786000 TI - The plight of the peer reviewer. PMID- 11786001 TI - Contrast media--a contradiction? PMID- 11786003 TI - Contrast media--why the confusion? PMID- 11786006 TI - Reducing child witnesses' false reports of misinformation from parents. AB - This study explored whether a source-monitoring training (SMT) procedure, in which children distinguished between events they recently witnessed versus events they only heard described, would help 3- to 8-year-olds to report only experienced events during a target interview. Children (N = 132) who witnessed science demonstrations and subsequently heard their parents describe nonexperienced events received SMT before or after a forensic-style interview. SMT reduced the number of false reports that 7- and 8-year-old children reported in response to direct questions but had no impact on the performance of younger children. Combined with earlier results, these data suggest a transition between 3 and 8 years of age in the strategic use of source-monitoring information to support verbal reports, such that only 7- and 8-year-olds generalize training to a difficult memory task that does not include mention of specific alternative sources. PMID- 11786007 TI - The association between auditory memory span and speech rate in children from kindergarten to sixth grade. AB - This study reexamined the association between speech rate and memory span in children from kindergarten to sixth grade (N = 152) in order to potentially account for the inconsistencies within the published literature on this topic. Some of the inconsistencies in past research may reflect the different methods adopted in assessing speech rate. In particular, repeating word triples may itself involve memory demands, contaminating the correlation between speech rate and memory span in younger children. Analyses using composite speech rate and memory span measures showed that speech rate for word triples shared variance with memory span that was independent of speech rate for single words. Moreover, speech rate for word triples was largely redundant with age in explaining additional variation in memory span once the effects of speech rate for single words were controlled. PMID- 11786008 TI - Age, memory load, and individual differences in working memory as determinants of class-inclusion reasoning. AB - We studied the effects of individual differences in speak-span scores and variations in memory demands on the class-inclusion performance of 10-, 13-, and 15-year-old children. The speak-span task was an age-appropriate modification of Daneman and Carpenter's (1980) reading-span task and was considered to be a measure of global resources. The age variable was assumed to be a global index of skill development, and some of the specific skills hypothesized to be important in class-inclusion reasoning were estimated using a mathematical model. The results from both regression analyses and the mathematical model indicated that differences in age, speak span, and memory load all affected performance. Surprisingly, the effects of speak span and memory load were independent. However, the effects of each of these variables depended on the age level of the participants. Based on these findings, we argued that (a) resources vary continuously with age, (b) both skill level and global resources should be varied in developmental studies of problem solving, and (c) resource theories (e.g., Norman & Shallice, 1986) should be modified to account for developmental change. PMID- 11786009 TI - The development of visual search in infants and very young children. AB - In two experiments, 90 1- to 3-year-olds were trained in a new nonverbal task to touch a video screen that displayed a unique target resembling a popular television character. The target appeared among varying numbers of distractors that resembled another familiar television character and was either a uniquely colored shape (the feature search task) or a unique color-shape combination (the conjunction search task). Each correct response triggered a sound and produced four animated objects on the screen. Irrespective of age and experimental design (between-subjects or within-subjects), children's reaction time (RT) patterns resembled those obtained from adults in corresponding search tasks: The RT slope for feature search was flat and independent of distractor number, whereas the RT slope for conjunction search increased linearly with distractor number. These results extend visual search effects found with adults to infants and very young children and suggest that the basic perceptual processes underlying visual search are qualitatively invariant over ontogeny. PMID- 11786010 TI - Transcription regulation in thermophilic bacteria: high resolution contact probing of Bacillus stearothermophilus and Thermotoga neapolitana arginine repressor-operator interactions. AB - Arginine-mediated regulation is remarkably well conserved in very divergent bacteria, and shows a number of unusual features that distinguish arginine regulation from other transcriptional control mechanisms. The arginine repressor subunit consists of a basic N-terminal DNA-binding domain, which belongs to the winged helix-turn-helix family, connected through a flexible linker to an acidic C-terminal domain responsible for binding of arginine and assembly of the high affinity holohexamer, which binds an approximately 40 bp target. To gain further insight into the molecular details of arginine repressor-operator interactions we have established a high resolution contact map of the argC operator from Bacillus stearothermophilus, a moderate thermophilic Gram-positive bacterium, and the argR operator from Thermotoga neapolitana, a Gram-negative hyperthermophile, with the corresponding ArgR proteins. Enzymatic and chemical footprinting have been combined with missing contact, pre-modification, base substitution, and small ligand binding interference techniques to gather information on backbone and base specific contacts with major and minor groove determinants of the operators. Wild type and mutant argC operators have been compared for their interaction with the repressor, using both in vivo and in vitro approaches. Our results indicate that the operators of B. stearothermophilus and T. neapolitana consist of two ARG box like sequences, 18 bp imperfect palindromes, separated by two and three base pairs, respectively, and that the repressors from thermophilic origin establish base-specific contacts with two major groove segments and the intervening minor groove of each ARG box, all aligned on one face of the helix. In contrast, no specific contacts are established in the minor groove facing the repressor in the centre of the operator, nevertheless this region plays a crucial structural role in complex formation, as indicated by mutant studies. This picture is reminiscent of arginine repressor binding in Escherichia coli, and therefore reinforces the uniform view of arginine regulation, but also reveals a number of striking differences at particular positions of the boxes and in the length and base-pair composition of the spacer connecting two ARG boxes in the operator. These might be responsible, in part, for subtle but important functional and mechanistic differences in the way species-specific repressors interact with their cognate target sites. These variations are underlined by the different behaviour of the repressors from E. coli, B. stearothermophilus and T. neapolitana in their potential to bind heterologous operators, their requirement for arginine, and the resistance of complex formation to non-specific competitor DNA. Our findings are discussed in view of the crystal structure of the arginine repressor from B. stearothermophilus. PMID- 11786011 TI - Characterization of activating region 3 from Escherichia coli FNR. AB - Transcription activation of anaerobically induced genes in Escherichia coli is mediated through the action of the global anaerobic regulator FNR. Although regions of FNR involved in FNR-dependent transcription activation have been identified, the side-chains critical to the function of these regions are not known. In this study, alanine-scanning of amino acid residues 80-89 of FNR activating region 3 (FNR-AR3) was used to determine which amino acid side-chains are required for transcription activation of class II FNR-dependent promoters. In vivo beta-galactosidase assays and in vitro transcription activation assays showed that Ala substitution of Ile81, Gly85 and Asp86 had the largest transcription activation defects, while comparison of the activity of single and double mutants indicated that Thr82, Glu83, Glu87 and Gln88 may contribute in a minor way to FNR-AR3 function. Site-directed mutagenesis of positions 81 and 86 showed that the hydrophobicity of Ile81 and the negative charge of Asp86 were important to FNR-AR3's function. Lastly, substitution of residues of E. coli FNR AR3 with those more basic residues found in a subset of FNR homologs, such as Rhodobacter sphaeroides FnrL, resulted in a mutant strain that was unable to activate transcription from E. coli class II FNR-dependent promoters. In conclusion, this study demonstrates a requirement for negatively charged and hydrophobic side-chain residues in E. coli FNR-AR3 function, although there is likely to be some variability in the characteristics of this region in other members of the FNR family. PMID- 11786012 TI - Duration and fitness dependence of quasispecies memory. AB - The duration and fitness dependence of memory in viral quasispecies evolving in cell culture have been investigated using two genetic markers of foot-and-mouth disease virus (FMDV). In lineages of antigenic variant FMDV RED, which reverted to FMDV RGD, memory FMDV RED genomes were detected after 50 infectious cycles, and memory level was fitness dependent. In growth-competition experiments between a reference FMDV RGD and two different FMDV RED populations, a 7.6-fold higher fitness of the initial FMDV RED population resulted in 30 to 100-fold higher memory level. In lineages of low-fitness clones containing an elongated internal polyadenylate tract, revertants lacking excess adenylate residues became dominant by passage 20. However, genomes including a larger number of adenylate residues were detected as memory genomes after at least 150 infectious cycles. Thus, quasispecies memory can be durable and is fitness dependent, as predicted from the growth competition of two mutant forms of a genome. An understanding of factors influencing quasispecies memory levels and duration may have implications for the extended diagnosis of viruses based on the quantification of minority genomes. PMID- 11786013 TI - Productive folding to the native state by a group II intron ribozyme. AB - Group II introns are large catalytic RNA molecules that fold into compact structures essential for the catalysis of splicing and intron mobility reactions. Despite a growing body of information on the folded state of group II introns at equilibrium, there is currently no information on the folding pathway and little information on the ionic requirements for folding. Folding isotherms were determined by hydroxyl radical footprinting for the 32 individual protections that are distributed throughout a group II intron ribozyme derived from intron ai5gamma. The isotherms span a similar range of Mg(2+) concentrations and share a similar index of cooperativity. Time-resolved hydroxyl radical footprinting studies show that all regions of the ribozyme fold slowly and with remarkable synchrony into a single catalytically active structure at a rate comparable to those of other ribozymes studied thus far. The rate constants for the formation of tertiary contacts and recovery of catalytic activity are identical within experimental error. Catalytic activity analyses in the presence of urea provide no evidence that the slow folding of the ai5gamma intron is attributable to the presence of unproductive kinetic traps along the folding pathway. Taken together, the data suggest that the rate-limiting step for folding of group II intron ai5gamma occurs early along the reaction pathway. We propose that this behavior resembles protein folding that is limited in rate by high contact order, or the need to form key tertiary interactions from partners that are located far apart in the primary or secondary structure. PMID- 11786014 TI - The HIV plus-strand transfer reaction: determination of replication-competent intermediates and identification of a novel lentiviral element, the primer over extension sequence. AB - Current retroviral replication models propose that during (+) strand synthesis, the initial (-) strand tRNA primer is partially replicated to reproduce the 18 nt primer-binding site (PBS). Subsequent removal of the tRNA primer from the (-) strand template exposes the PBS, which anneals to complementary sequences on a DNA acceptor template to enable (+) strand transfer. We used model templates composed of primed (-) strand DNA covalently linked with post-transcriptionally modified tRNA(3)(lys) along with natural sequence human immunodeficiency virus (HIV) acceptor DNA to study the generation of the (+) strand strong stop intermediate and the subsequent (+) strand transfer reaction. The rate of formation of the (+) strand transfer reaction products was modestly increased (threefold) by inclusion of nucleocapsid protein, suggesting an ancillary role for this protein in this stage of retroviral replication. In addition to the well known stop site opposite G59 of the tRNA primer, we detected two additional stop sites opposite psi55 and at A38. Kinetic analysis showed that only the intermediates formed by stops opposite G59 and psi55 were active in the subsequent (+) strand transfer reaction. The surprising discovery of the longer, viable (+) strand interaction intermediate prompted us to survey retroviral sequences for a region complementary to the additional donor DNA nucleotides involved in this over-extension. Indeed, complementary sequences that could support this over-extension were found. A strong consensus sequence is immediately adjacent to and downstream of the PBS in lentiviruses and spumaviruses. This consensus sequence was not found in other genera of retroviruses. We have named this element the "primer over-extension sequence" (POS), and propose that it provides a complementary sequence for strand transfer reactions proceeding from intermediates that extend beyond the standard 18 nt complement of the PBS. PMID- 11786015 TI - Increasing the thermal stability of an oligomeric protein, beta-glucuronidase. AB - The reporter enzyme beta-glucuronidase was mutagenized and evolved for thermostability. After four cycles of screening the best variant was more active than the wild-type enzyme, and retained function at 70 degrees C, whereas the wild-type enzyme lost function at 65 degrees C. Variants derived from sequential mutagenesis were shuffled together, and re-screened for thermostability. The best variants retained activities at even higher temperatures (80 degrees C), but had specific activities that were now less than that of the wild-type enzyme. The mutations clustered near the tetramer interface of the enzyme, and many of the evolved variants showed much greater resistance to quaternary structure disruption at high temperatures, which is also a characteristic of naturally thermostable enzymes. Together, these results suggest a pathway for the evolution of thermostability in which enzymes initially become stable at high temperatures without loss of activity at low temperatures, while further evolution leads to enzymes that have kinetic parameters that are optimized for high temperatures. PMID- 11786016 TI - Structure-based design and study of non-amyloidogenic, double N-methylated IAPP amyloid core sequences as inhibitors of IAPP amyloid formation and cytotoxicity. AB - Pancreatic amyloid is formed by the aggregation of the 37-residue islet amyloid polypeptide (IAPP) in type II diabetes patients and is cytotoxic. Pancreatic amyloid deposits are found in more than 95 % of type II diabetes patients and their formation is strongly associated with disease progression. IAPP amyloid forms via a conformational transition of soluble IAPP into aggregated beta sheets. We recently identified IAPP(22-27) (NFGAIL) as a minimum length sequence sufficient to self-associate into beta-sheet-containing amyloid fibrils. Here, we have used the NFGAIL model of the IAPP amyloid core as a structural template to design non-amyloidogenic derivatives of amyloidogenic sequences of IAPP that are able to interact with the native sequences and inhibit amyloid formation. The design of the derivatives was based on a simple, structure-based minimalistic and selective N-methylation approach. Accordingly, a minimum number of two amide bonds on the same side of the beta-strand of the amyloid core was N-methylated. This was expected to eliminate the two intermolecular backbone NH to CO hydrogen bonds which are critical for the extension of the beta-sheet dimers into multimers and amyloid. Other beta-strand "contact sides" remained intact allowing for the derivatives to interact with the native sequences. Double N-methylated derivatives of amyloidogenic and cytotoxic partial IAPP sequences generated included F(N-Me)GA(N-Me)IL, NF(N-Me)GA(N-Me)IL, SNNF(N-Me)GA(N-Me)IL, and SNNF(N Me)GA(N-Me)ILSS and were found to be devoid of beta-sheet structure, amyloidogenicity and cytotoxicity according to Fourier transform-infrared spectroscopy (FT-IR), Congo red (CR) staining, electron microscopy (EM), and cell viability tests. The derivatives were able to interact with the native sequences and inhibit amyloid formation as shown by circular dichroism spectroscopy (CD), FT-IR and EM. Moreover, SNNF(N-Me)GA(N-Me)ILSS inhibited cytotoxicity of SNNFGAILSS and is thus the first reported inhibitor of IAPP amyloid formation and cytotoxicity. Our results demonstrate the validity of the design approach for IAPP and suggest that it may find application in understanding the structural features of amyloid formation and in the development of inhibitors of amyloid formation and cytotoxicity of other amyloidogenic polypeptides as well. PMID- 11786017 TI - Open and closed conformation of the E. coli purine nucleoside phosphorylase active center and implications for the catalytic mechanism. AB - The crystal structure of the ternary complex of hexameric purine nucleoside phosphorylase (PNP) from Escherichia coli with formycin A derivatives and phosphate or sulphate ions is determined at 2.0 A resolution. The hexamer is found as a trimer of unsymmetric dimers, which are formed by pairs of monomers with active sites in different conformations. The conformational difference stems from a flexible helix (H8: 214-236), which is continuous in one conformer, and segmented in the other. With the continuous helix, the entry into the active site pocket is wide open, and the ligands are bound only loosely ("open" or "loose binding" conformation). By segmentation of the helix (H8: 214-219 and H8': 223 236, separated by a gamma-turn), the entry into the active site is partially closed, the pocket is narrowed and the ligands are bound much more tightly ("closed" or "tight binding" conformation). Furthermore, the side-chain of Arg217 is carried by the moving helix into the active site. This residue, conserved in all homologous PNPs, plays an important role in the proposed catalytic mechanism. In this mechanism, substrate binding takes place in the open, and and the catalytic action occurs in the closed conformation. Catalytic action involves protonation of the purine base at position N7 by the side-chain of Asp204, which is initially in the acid form. The proton transfer is triggered by the Arg217 side-chain which is moved by the conformation change into hydrogen bond distance to Asp204. The mechanism explains the broad specificity of E. coli PNP, which allows 6-amino as well as 6-oxo-nucleosides as substrates. The observation of two kinds of binding sites is fully in line with solution experiments which independently observe strong and weak binding sites for phosphate as well as for the nucleoside inhibitor. PMID- 11786018 TI - Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases. AB - The repair of T:G mismatches in DNA is key for maintaining bacterial restriction/modification systems and gene silencing in higher eukaryotes. T:G mismatch repair can be initiated by a specific mismatch glycosylase (MIG) that is homologous to the helix-hairpin-helix (HhH) DNA repair enzymes. Here, we present a 2.0 A resolution crystal structure and complementary mutagenesis results for this thermophilic HhH MIG enzyme. The results suggest that MIG distorts the target thymine nucleotide by twisting the thymine base approximately 90 degrees away from its normal anti position within DNA. We propose that functionally significant differences exist in DNA repair enzyme extrahelical nucleotide binding and catalysis that are characteristic of whether the target base is damaged or is a normal base within a mispair. These results explain why pure HhH DNA glycosylases and combined glycosylase/AP lyases cannot be interconverted by simply altering their functional group chemistry, and how broad-specificity DNA glycosylase enzymes may weaken the glycosylic linkage to allow a variety of damaged DNA bases to be excised. PMID- 11786019 TI - Active site structure and stereospecificity of Escherichia coli pyridoxine-5' phosphate oxidase. AB - Pyridoxine-5'-phosphate oxidase catalyzes the oxidation of either the C4' alcohol group or amino group of the two substrates pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate to an aldehyde, forming pyridoxal 5'-phosphate. A hydrogen atom is removed from C4' during the oxidation and a pair of electrons is transferred to tightly bound FMN. A new crystal form of the enzyme in complex with pyridoxal 5'-phosphate shows that the N-terminal segment of the protein folds over the active site to sequester the ligand from solvent during the catalytic cycle. Using (4'R)-[(3)H]PMP as substrate, nearly 100 % of the radiolabel appears in water after oxidation to pyridoxal 5'-phosphate. Thus, the enzyme is specific for removal of the proR hydrogen atom from the prochiral C4' carbon atom of pyridoxamine 5'-phosphate. Site mutants were made of all residues at the active site that interact with the oxygen atom or amine group on C4' of the substrates. Other residues that make interactions with the phosphate moiety of the substrate were mutated. The mutants showed a decrease in affinity, but exhibited considerable catalytic activity, showing that these residues are important for binding, but play a lesser role in catalysis. The exception is Arg197, which is important for both binding and catalysis. The R197 M mutant enzyme catalyzed removal of the proS hydrogen atom from (4'R)-[(3)H]PMP, showing that the guanidinium side-chain plays an important role in determining stereospecificity. The crystal structure and the stereospecificity studies suggests that the pair of electrons on C4' of the substrate are transferred to FMN as a hydride ion. PMID- 11786020 TI - The high-affinity interaction of human IL-4 and the receptor alpha chain is constituted by two independent binding clusters. AB - IL4-BP, the extracellular binding domain of the IL-4 receptor alpha chain, contains a high-affinity binding epitope for IL-4 (K(D) 150 pM). Previous results on the crystal structure of the IL-4/IL4-BP complex and on the functional epitope of IL-4 suggested that this contact comprises a mosaic of two binding clusters. The present mutational analysis of IL4-BP supports this view and demonstrates that the energetically most important group is the receptor carboxylate group of D72 forming an ion pair with IL-4 R88 in cluster II. The second main receptor determinant is the hydroxyl group of Y183 forming a hydrogen bond with IL-4 E9 in cluster I. The latter is engaged in additional hydrogen bonds with Y13 and also in van der Waals contacts with Y127. Receptor residue D72 as well as Y183 are each surrounded by a shell of hydrophobic groups from residues that upon mutation lead to smaller decreases in binding affinity. Analysis of IL4-BP double mutants showed that receptor side-chains within one cluster but not those of different clusters cooperate. Interaction analysis of IL-4 and IL4-BP single mutants also revealed additivity in binding of side-chains between clusters and cooperativity within each cluster I or II.These results show that the high-affinity IL-4/IL4-BP contact is constituted by two independent binding units, each containing a central polar or charged side-chain surrounded by hydrophobic groups (avocado cluster). PMID- 11786021 TI - Activation of ribokinase by monovalent cations. AB - Carbohydrate kinases frequently require a monovalent cation for their activity. The physical basis of this phenomenon is, however, usually unclear. We report here that Escherichia coli ribokinase is activated by potassium with an apparent K(d) of 5 mM; the enzyme should therefore be fully activated under physiological conditions. Cesium can be used as an alternative ion, with an apparent K(d) of 17 mM. An X-ray structure of ribokinase in the presence of cesium was solved and refined at 2.34 A resolution. The cesium ion was bound between two loops immediately adjacent to the anion hole of the active site. The buried location of the site suggests that conformational changes will accompany ion binding, thus providing a direct mechanism for activation. Comparison with structures of a related enzyme, the adenosine kinase of Toxoplasma gondii, support this proposal. This is apparently the first instance in which conformational activation of a carbohydrate kinase by a monovalent cation has been assigned a clear structural basis. The mechanism is probably general to ribokinases, to some adenosine kinases, and to other members of the larger family. A careful re-evaluation of the biochemical and structural data is suggested for other enzyme systems. PMID- 11786022 TI - Crystal structure of the flavoprotein domain of the extracellular flavocytochrome cellobiose dehydrogenase. AB - Cellobiose dehydrogenase (CDH) participates in the degradation of cellulose and lignin. The protein is an extracellular flavocytochrome with a b-type cytochrome domain (CYT(cdh)) connected to a flavodehydrogenase domain (DH(cdh)). DH(cdh) catalyses a two-electron oxidation at the anomeric C1 position of cellobiose to yield cellobiono-1,5-lactone, and the electrons are subsequently transferred from DH(cdh) to an acceptor, either directly or via CYT(cdh). Here, we describe the crystal structure of Phanerochaete chrysosporium DH(cdh) determined at 1.5 A resolution. DH(cdh) belongs to the GMC family of oxidoreductases, which includes glucose oxidase (GOX) and cholesterol oxidase (COX); however, the sequence identity with members of the family is low. The overall fold of DH(cdh) is p hydroxybenzoate hydroxylase-like and is similar to, but also different from, that of GOX and COX. It is partitioned into an FAD-binding subdomain of alpha/beta type and a substrate-binding subdomain consisting of a seven-stranded beta sheet and six helices. Docking of CYT(cdh) and DH(cdh) suggests that CYT(cdh) covers the active-site entrance in DH(cdh), and that the resulting distance between the cofactors is within acceptable limits for inter-domain electron transfer. Based on docking of the substrate, cellobiose, in the active site of DH(cdh), we propose that the enzyme discriminates against glucose by favouring interaction with the non-reducing end of cellobiose. PMID- 11786023 TI - Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR). AB - Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that acts as a molecular scaffold to promote signal transmission from Raf-1 to MEK and MAPK. All KSR proteins contain a conserved cysteine-rich C1 domain, and studies have implicated this domain in the regulation of KSR1 subcellular localization and function. To further elucidate the biological role of the KSR1 C1 domain, we have determined its three-dimensional solution structure using nuclear magnetic resonance (NMR). We find that while the overall topology of the KSR1 C1 domain is similar to the C1 domains of Raf-1 and PKCgamma, the predicted ligand-binding region and the surface charge distribution are unique. Moreover, by generating chimeric proteins in which these domains have been swapped, we find that the C1 domains of Raf-1, PKCgamma, and KSR1 are not functionally interchangeable. The KSR1 C1 domain does not bind with high affinity or respond biologically to phorbol esters or ceramide, and it does not interact directly with Ras, indicating that the putative ligand(s) for the KSR1 C1 domain are distinct from those that interact with PKCgamma and Raf-1. In addition, our analysis of the chimeric proteins supports the model that Raf-1 is a ceramide-activated kinase and that its C1 domain is involved in the ceramide-mediated response. Finally, our findings demonstrate an absolute requirement of the KSR1 C1 domain in mediating the membrane localization of KSR1, a crucial feature of its scaffolding activity. Together, these results underscore the functional specificity of these important regulatory domains and demonstrate that the structural features of the C1 domains can provide valuable insight into their ligand-binding properties. PMID- 11786024 TI - Protein folding and stability of human CDK inhibitor p19(INK4d). AB - P19(INK4d) is a tumor suppressing protein and belongs to a family of cyclin D dependent kinase inhibitors of CDK4 and CDK6, which play a key role in human cell cycle control. P19 comprises ten alpha-helices arranged sequentially in five ankyrin repeats forming an elongated structure. This rather simple topology, combined with its physiological function, makes p19 an interesting model protein for folding studies. Urea-induced unfolding transitions monitored by far-UV CD and phenylalanine fluorescence coincide and suggest a two-state mechanism for equilibrium unfolding. Unfolding of p19 followed by 2D (1)H-(15)N HSQC spectra revealed a third species at moderate urea concentrations with a maximum population of about 30 % near 3.2 M urea. It shows poor chemical shift dispersion, but cross-peaks emerge for some residues that are distinct from the native or unfolded state. This equilibrium intermediate either arises only at high protein concentrations (as in the NMR experiment) or has similar optical properties to the unfolded state. Stopped-flow far-UV CD experiments at various urea concentrations revealed that alpha-helical structure is formed in three phases, of which only the fastest phase (10 s(-1)) depends upon the urea concentration. The kinetic of the slowest phase (0.017 s(-1)) can be resolved by 1D real-time NMR and accelerated by cyclophilin. It is limited in rate by prolyl isomerization, and native-like ordered structure cannot form prior to this isomerization. The two fast phases lead to 83 % native protein within the dead time of the NMR experiment. In contrast to p16(INK4a), which exhibits only a marginal stability and high unfolding rates, p19 shows the expected stability for a protein of this size with a clear kinetic barrier between the unfolded and folded state. Therefore, p19 might complement the function of less stable INK4 inhibitors in cell cycle control under unfavorable conditions. PMID- 11786025 TI - Evidence for an internal entropy contribution to phosphoryl transfer: a study of domain closure, backbone flexibility, and the catalytic cycle of cAMP-dependent protein kinase. AB - While there is no question that ligands can induce large-scale domain movements that narrow (close) the active-site cleft of the catalytic (C) subunit of cAMP dependent protein kinase (cAPK), the results from small-angle X-ray scattering, protein footprinting, and thermostability studies are inconsistent with regard to which ligands induce these movements. This inconsistency suggests a greater complexity of cAPK conformational dynamics than is generally recognized. As an initial step to study this issue in relation to the catalysis, a new method to measure cAPK domain closure was developed, and the state of domain closure and the local segmental flexibility at major steps of the cAPK catalytic cycle were examined with site-directed labeling and fluorescence spectroscopy. To achieve this, a C subunit mutant (F239C/C199A) was engineered that allowed for fluorescein 5-maleimide (donor) conjugation of F239C in the large lobe and tetramethylrhodamine (acceptor) conjugation of C343 in the small lobe. Domain closure was assessed as an increase in the efficiency of energy transfer between donor and acceptor. The anisotropy decay of fluoroscein 5-maleimide, conjugated to a site of cysteine substitution (K81C) in the small lobe of the C subunit was used to assess the local backbone flexibility around the B helix. The effects of substrate/pseudosubstrate (ATP and PKI(5-24)), a fragment of protein kinase inhibitor) and products (ADP and phosphorylated PKS) on domain closure and B helix flexibility were measured. The results show that domain closure is not tightly coupled to the flexibility around K81C. Moreover, although substrates/pseudosubstrate and products independently close the active-site cleft, only the substrates substantially decreased the backbone flexibility around the B helix. Because this order-to-disorder transition coincides with the phosphoryl transfer transition, the results suggest the existence of an internal entropy contribution to catalysis. PMID- 11786026 TI - Accurate computer-based design of a new backbone conformation in the second turn of protein L. AB - The rational design of loops and turns is a key step towards creating proteins with new functions. We used a computational design procedure to create new backbone conformations in the second turn of protein L. The Protein Data Bank was searched for alternative turn conformations, and sequences optimal for these turns in the context of protein L were identified using a Monte Carlo search procedure and an energy function that favors close packing. Two variants containing 12 and 14 mutations were found to be as stable as wild-type protein L. The crystal structure of one of the variants has been solved at a resolution of 1.9 A, and the backbone conformation in the second turn is remarkably close to that of the in silico model (1.1 A RMSD) while it differs significantly from that of wild-type protein L (the turn residues are displaced by an average of 7.2 A). The folding rates of the redesigned proteins are greater than that of the wild type protein and in contrast to wild-type protein L the second beta-turn appears to be formed at the rate limiting step in folding. PMID- 11786027 TI - Why are proteins so robust to site mutations? AB - There have been repeated observations that proteins are surprisingly robust to site mutations, enduring significant numbers of substitutions with little change in structure, stability, or function. These results are almost paradoxical in light of what is known about random heteropolymers and the sensitivity of their properties to seemingly trivial mutations. To address this discrepancy, the preservation of biological protein properties in the presence of mutation has been interpreted as indicating the independence of selective pressure on such properties. Such results also lead to the prediction that de novo protein design should be relatively easy, in contrast to what is observed. Here, we use a computational model with lattice proteins to demonstrate how this robustness can result from population dynamics during the evolutionary process. As a result, sequence plasticity may be a characteristic of evolutionarily derived proteins and not necessarily a property of designed proteins. This suggests that this robustness must be re-interpreted in evolutionary terms, and has consequences for our understanding of both in vivo and in vitro protein evolution. PMID- 11786028 TI - Mathematical modelling of nitric oxide regulation of rete peg formation in psoriasis. AB - Recent experiments have shown that in patients with psoriasis, highly elevated levels of nitric oxide (NO) are released at the surface of psoriatic plaques. Nitric oxide is a central biological regulator of many aspects of physiology, and it is a natural possibility that the high nitric oxide levels in psoriasis play a causal role in the onset of the disease. Here, we use mathematical modelling to investigate this possibility. We begin by discussing a simple model consisting of a single equation for nitric oxide concentration, which enables nitric oxide secretion rates in the basal epidermis to be calculated from the observed NO release rates at the skin surface. Using this key parameter value, we then develop an extended model that tests the hypothesis that nitric oxide regulates the formation of the extended rete pegs seen in psoriatic plaques. This occurs via the peroxynitrite-dependent activation of the collagenase MMP-8, which is produced by neutrophils present at high levels in psoriatic plaques. The plausibility of the hypothesis is demonstrated and specific testable quantitative predictions about the roles of the various cell types and signalling molecules are made. PMID- 11786029 TI - Calcium homeostasis and parturient hypocalcemia: an integral feedback perspective. AB - Calcium is tightly regulated in mammals because of the critical role of calcium ion concentrations in many physiological functions. In this work, we develop a model for calcium homeostasis and identify integral feedback control as a functional module that maintains this homeostasis. We argue that maintaining calcium concentrations in a narrow range and perfect adaptation seen when the calcium homeostatic mechanism is subjected to extreme disturbances are the result of a feedback control system implementing integral control through specific interactions of the regulating hormones. Based on the constraints imposed by the suggested integral control, we arrive at a simple dynamical model for calcium homeostasis. We show that the model is biologically plausible and is consistent with known physiology. Furthermore, the utility of the integral-feedback model is revealed by examining an extreme calcium perturbation, parturient paresis in dairy cows. PMID- 11786030 TI - Mathematical modelling of host-parasitoid systems: effects of chemically mediated parasitoid foraging strategies on within- and between-generation spatio-temporal dynamics. AB - In this paper we develop a novel discrete, individual-based mathematical model to investigate the effect of parasitoid foraging strategies on the spatial and temporal dynamics of host-parasitoid systems. The model is used to compare naive or random search strategies with search strategies that depend on experience and sensitivity to semiochemicals in the environment. It focuses on simple mechanistic interactions between individual hosts, parasitoids, and an underlying field of a volatile semiochemical (emitted by the hosts during feeding) which acts as a chemoattractant for the parasitoids. The model addresses movement at different spatial scales, where scale of movement also depends on the internal state of an individual. Individual interactions between hosts and parasitoids are modelled at a discrete (micro-scale) level using probabilistic rules. The resulting within-generation dynamics produced by these interactions are then used to generate the population levels for successive generations. The model simulations examine the effect of various key parameters of the model on (i) the spatio-temporal patterns of hosts and parasitoids within generations; (ii) the population levels of the hosts and parasitoids between generations. Key results of the model simulations show that the following model parameters have an important effect on either the development of patchiness within generations or the stability/instability of the population levels between generations: (i) the rate of diffusion of the kairomones; (ii) the specific search strategy adopted by the parasitoids; (iii) the rate of host increase between successive generations. Finally, evolutionary aspects concerning competition between several parasitoid subpopulations adopting different search strategies are also examined. PMID- 11786031 TI - Effects of intraguild predation on resource competition. AB - In this work, a simple Lotka-Volterra model of intraguild predation with three species is analysed, searching for the effect of the top predator on the coexistence with its prey-competitor species. Apart from the well-known result that the intraguild prey must be superior in the competition for the shared prey in order to make coexistence possible, the magnitude of intraguild predation and the form by which the intraguild predator makes use of the intraguild prey have important consequences upon the dynamics, extending or restricting the possibilities of coexistence. These results are easily obtained by nullcline analysis. Also, some interesting results are obtained for the same model but including saturating functional response. PMID- 11786032 TI - Homosexual tandem running as selfish herd in Reticulitermes speratus: novel antipredatory behavior in termites. AB - We investigated the predator avoidance mechanism of post-swarming alates of the lower subterranean termite, Reticulitermes speratus Kolbe. In some lower termites, homosexual tandem running is observed in addition to ordinary heterosexual tandem running. An experiment designed to compare the risk of predation by a termite-hunting ant, Brachyponera chinensis Emery, showed that homosexual tandem running reduced the predation risk until termites encounter the opposite sex. Since an individual ant cannot capture two dealates at once, one of the two dealates forming a tandem can escape while the ant captures its partner. Therefore, the "post-encounter risk" of individuals running in tandem was lower than that of single individuals. The "encounter risk" with predatory ants was also examined using a mathematical model considering the increased detectability of the predator due to enhanced size of the prey unit. It was suggested that tandem running reduces the predation risk of both participants, even when the enhanced encounter risk was taken into account. In males, competition for the back position was often observed, and consequently, the male at the back was always larger than the male in front. When a male-male tandem encountered a female, the back male won the female more often than the front male. This result suggested that male-male tandem running should result in selection pressure in favor of vigorous males. In conclusion, tandem running decreases the individual predation risk through the dilution effect, and it also plays a role as a mechanism of indirect sexual selection. PMID- 11786033 TI - Behavioral stochastic resonance: how the noise from a Daphnia swarm enhances individual prey capture by juvenile paddlefish. AB - Zooplankton emit weak electric fields into the surrounding water that originate from their own muscular activities associated with swimming and feeding. Juvenile paddlefish prey upon single zooplankton by detecting and tracking these weak electric signatures. The passive electric sense in this fish is provided by an elaborate array of electroreceptors, Ampullae of Lorenzini, spread over the surface of an elongated rostrum. We have previously shown that the fish use stochastic resonance to enhance prey capture near the detection threshold of their sensory system. However, stochastic resonance requires an external source of electrical noise in order to function. A swarm of plankton, for example Daphnia, can provide the required noise. We hypothesize that juvenile paddlefish can detect and attack single Daphnia as outliers in the vicinity of the swarm by using noise from the swarm itself. From the power spectral density of the noise plus the weak signal from a single Daphnia, we calculate the signal-to-noise ratio, Fisher information and discriminability at the surface of the paddlefish's rostrum. The results predict a specific attack pattern for the paddlefish that appears to be experimentally testable. PMID- 11786034 TI - Analysis of the kinetic and equilibrium binding of Ku protein to DNA. AB - The loading of Ku onto a DNA end in a double-strand DNA break is thought to be one of the first steps in the non-homologous DNA end joining (NHEJ) pathway, giving it an essential role in the maintenance of genomic integrity. The binding of Ku to DNA is complicated since DNA can accommodate multiple Ku subunits, which can translocate on the DNA strand. Furthermore, Ku may exhibit cooperativity in the loading process. Therefore, simple one- to-one kinetic models are unable to adequately simulate the process. However, through the use of computer simulation and curve-fitting, we are able to provide a comprehensive mechanistic model and rate constants that closely approximate experimental data for DNA molecules that bind one, two, and three Ku molecules under both kinetic and equilibrium conditions. The model obtains a best fit with Ku having a roughly seven-fold preference to bind to DNA ends rather than internal positions and is consistent with Ku having a strong preference of which face of the protein loads onto the DNA end. PMID- 11786035 TI - Evaluating phylogenetic tree shape: two modifications to Fusco & Cronk's method. AB - Measurement of the degree of asymmetry in phylogenetic trees is important because a tree's shape reflects the process by which it has grown. For example, highly asymmetric trees are evidence that species have had different potential for diversification. Of the tree shape measures in the literature, that proposed by Fusco & Cronk (J. theor. Biol.175, 235-243) appears to be particularly useful, because it does not require fully-resolved trees whose terminals are of equal taxonomic rank. The value of the asymmetry or imbalance at a node is intended to be independent of the number of species ultimately descended from the node. In this paper, however, we point out that the value does depend upon species number. We propose two modifications that remove the dependency and so increase the measure's usefulness. We illustrate the use of the modified measures, which are implemented in a freely-available program, MESA. PMID- 11786036 TI - Putting intentions into cell biochemistry: an artificial intelligence perspective. AB - The living cell exists by virtue of thousands of nonlinearly interacting processes. This complexity greatly impedes its understanding. The standard approach to the calculation of the behaviour of the living cell, or part thereof, integrates all the rate equations of the individual processes. If successful extremely intensive calculations often lead the calculation of coherent, apparently simple, cellular "decisions" taken in response to a signal: the complexity of the behavior of the cell is often smaller than it might have been. The "decisions" correspond to the activation of entire functional units of molecular processes, rather than individual ones. The limited complexity of signal and response suggests that there might be a simpler way to model at least some important aspects of cell function. In the field of Artificial Intelligence, such simpler modelling methods for complex systems have been developed. In this paper, it is shown how the Artificial Intelligence description method for deliberative agents functioning on the basis of beliefs, desires and intentions as known in Artificial Intelligence, can be used successfully to describe essential aspects of cellular regulation. This is demonstrated for catabolite repression and substrate induction phenomena in the bacterium Escherichia coli. The method becomes highly efficient when the computation is automated in a Prolog implementation. By defining in a qualitative way the food supply of the bacterium, the make-up of its catabolic pathways is readily calculated for cases that are sufficiently complex to make the traditional human reasoning tedious and error prone. PMID- 11786039 TI - International conference on emerging technologies in gene/drug therapy and molecular biology. Corfu, Greece, August 25-31, 2001. PMID- 11786040 TI - Use of perflubron to enhance lung gene expression: safety and initial efficacy studies in non-human primates. AB - Use of perflubron (LiquiVent) and other perfluorochemical liquids during intratracheal administration of adenovirus and AAV vectors has been shown to improve total gene expression as well as distribution of expression throughout lungs of spontaneously breathing rodents. To determine if this method could be safely and easily extended to non-human primates, we carried out a pilot investigation in six spontaneously breathing rhesus macaques. Two animals received bronchoscopic administration of recombinant adenovirus vector (type 5 E1 deleted AdCMVlacZ, 4.6 x 10(10) plaque forming units/animal), two animals received vector followed by instillation of perflubron, and two animals received perflubron alone. Instillation of perflubron was well tolerated by the animals and, once recovered from anesthesia, all animals behaved and fed normally until lung harvest. Serial X-rays demonstrated that the perflubron had cleared from lungs of three animals by 48 hours after administration; the fourth animal had a small amount of residual perflubron. Apart from a mild elevation in hepatocellular enzymes, no significant abnormality was noted in complete blood count or serum electrolytes and chemistries. In animals receiving either vector alone or vector with perflubron, in situ beta-galactosidase expression was observed in a variety of cells including large airway, bronchiolar, and alveolar epithelial cells. In summary, use of perflubron was well tolerated in spontaneously breathing macaques. Further studies in larger numbers of animals will help assess the potential efficacy of perflubron for enhancing gene expression and elucidate effects on local and systemic inflammatory responses. PMID- 11786041 TI - Viral-mediated gene transfer to mouse primary neural progenitor cells. AB - Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. To address this issue, we cultured cells from embryonic day 16-18 mouse brain in serum-free medium containing epidermal growth factor or basic fibroblast growth factor, and investigated how transduction with recombinant viral vectors affected maintenance and differentiation properties of progenitor cells. Neurosphere cultures were incubated with feline immunodeficiency virus (FIV), adeno-associated virus (AAV) or ade-noviral (Ad) constructs expressing either beta-galactosidase or enhanced green fluorescent protein at low multiplicity of infection. Nestin-positive neurospheres were regenerated after incubation of single progenitor cells with FIV, indicating that FIV-mediated gene transfer did not inhibit progenitor cell self-renewal. In contrast, adenovirus induced differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes. The AAV serotypes tested did not effectively transduce progenitor cells. FIV-transduced progenitors retained the potential for differentiation into neurons and glia in vitro, and when transplanted into the striatum of normal adult C57BL/6 mice differentiated into glia, or remained undifferentiated. In the presence of tumor cells, FIV-transduced progenitors migrated significantly from the injection site. Our results suggest that FIV based vectors can transduce progenitor cell populations in vitro, with maintenance of their ability to differentiate into multiple cell types or to respond to injury within the central nervous system. These results hold promise for the use of genetically manipulated stem cells for CNS therapies. PMID- 11786042 TI - Neurotropism and retrograde axonal transport of a canine adenoviral vector: a tool for targeting key structures undergoing neurodegenerative processes. AB - Viral tropism refers to the ability of a virus to selectively infect a given subset of cells. It relies on a variety of viral and host determinants that entail virus binding and entry into target cells, in addition to the presence of genetic elements that allow or enhance viral gene expression in a specific manner. Here we report the results of neuroanatomical studies in rat brains injected in different cerebral structures with vectors derived from the canine adenovirus type 2 (CAV2), whose natural target is the respiratory epithelium. Control animals injected with vectors derived from the human adenovirus type 5 (Ad5) displayed the previously documented pattern of gene transfer into both neurons and glial cells. Injection of CAV2 vectors resulted in selective transduction of neuronal cells. Cy3-labeled CAV2 particles allowed us to establish the high affinity of this vector for neuronal processes in vitro and their rapid uptake and retrograde axonal transport in vivo. After intrahippocampal injections, labeled particles were found, within 1 hour, closely associated to the nuclei of the neurons in layer II of the entorhinal cortex. Injections into the striatum resulted in a massive transduction of dopaminergic neurons in the substantia nigra compacta. The high efficiency with which CAV2 vectors are retrogradely transported opens the possibility of targeting a transgene to neuron populations remote from the injection site and difficult to access. Our data support the possibility to target key structures undergoing a degenerative process: the enthorhinal cortex, which is affected first in Alzheimer's disease; and the substantia nigra compacta, which undergoes degeneration in Parkinson's disease. PMID- 11786043 TI - Combination genetic therapy to inhibit HIV-1. AB - Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance efficacy similarly, but delivery of even single genes to high percentages of hematopoietic cells or their derivatives has proven problematic. Because of their high efficiency of gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each carrying a different transgene that targeted a different lentiviral function. We tested the ability of these constructs, individually and in double and triple combinations, to protect SupT1 human T lymphoma cells from HIV-1 challenge. Single chain antibodies (SFv) against CXCR4 and against HIV-1 reverse transcriptase (RT) and integrase (IN) were used, as were polymeric TAR decoys (PolyTAR) and a dominant-negative mutant of HIV-1 Rev (RevM10). Immunostaining showed that virtually all doubly treated cells expressed both transgenes. All transgenes individually protected from HIV-1 but, except for anti-CXCR4 SFv, their effectiveness diminished as challenge doses increased from 40 through 2500 tissue culture infectious dose(50) (TCID(50))/10(6) cells. However, all combinations of transgenes protected target cells better than individual transgenes, even from the highest challenge doses. Thus, combination gene therapies may inhibit HIV-1 better than single agents, and rSV40s may facilitate delivery of multigene therapeutics. PMID- 11786044 TI - Neurological correction of lysosomal storage in a mucopolysaccharidosis IIIB mouse model by adeno-associated virus-mediated gene delivery. AB - Mucopolysaccharidosis (MPS) IIIB is characterized by mild somatic features and severe neurological diseases leading to premature death. No definite treatment is available for MPS IIIB patients. We constructed two recombinant adeno-associated virus (rAAV) vectors containing the human alpha-N-acetylglucosaminidase (NaGlu) cDNA driven by either a CMV or a neuron-specific enolase (NSE) promoter. In vitro, these rAAV vectors mediated efficient expression of recombinant NaGlu in human MPS IIIB fibroblasts and mouse MPS IIIB somatic and brain primary cell cultures. The secreted rNaGlu was taken up by both human and mouse MPS IIIB cells in culture and degraded the accumulated glycosaminoglycans (GAG). A direct microinjection (10(7) viral particles, 1 microl/10 minutes per injection) of vectors containing the NSE promoter resulted in long-term (6 months, the duration of the experiments) expression of rNaGlu in multiple brain structures/areas of adult MPS IIIB mice. Consistent with previous studies, the main target cells were neurons. However, while vector typically transduced an area of 400-500 microm surrounding the infusion sites, the correction of GAG storage involved neurons of a much broader area (1.5 mm) in a 6-month duration of experiments. These results provide a basis for the development of a treatment for neurological disease in MPS IIIB patients using AAV vectors. PMID- 11786045 TI - Targeted retrograde gene delivery for neuronal protection. AB - The cellular heterogeneity and complex circuitry of the central nervous system make it difficult to achieve precise delivery of experimental and therapeutic agents. We report here an in vivo retrograde gene delivery strategy to target mature projection neurons using adeno-associated virus, a vector with low toxicity and the capacity for long-term gene expression. Viral delivery to axon terminal fields in the hippocampus and striatum resulted in viral internalization, retrograde transport, and transgene expression in specific projection neurons in entorhinal cortex and substantia nigra. Retrograde delivery of the anti-apoptotic gene Bcl2l (also known as Bcl-xL) protected entorhinal projection neurons from subsequent damage-induced cell death. Given the broad distribution of neurons affected by neurodegenerative diseases, gene delivery to both the terminal fields and the projection neurons through retrograde infection provides for strategic therapeutic intervention at both levels of the neural circuit. This approach may also facilitate experimental studies of defined neural circuits. PMID- 11786046 TI - Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution. AB - Intradermal injection of naked DNA results in gene transfer to skin cells, but the efficiency of this gene transfer method is relatively low and variable. We have systematically optimized several parameters to obtain reproducible, high level gene transfer to the mouse skin. Older mice (approximately 7 weeks) showed a significant decrease in gene expression compared with younger mice (4-5 weeks old). The composition of the solvent vehicle (electrolyte versus nonelectrolyte) strongly affected gene expression in the skin. A higher level of gene expression was achieved when naked DNA was dissolved in isotonic phosphate buffered saline solution compared with isotonic dextrose solution. Finally, transfection efficiency in older mice was greatly improved by increasing the ionic strength of the solvent vehicle. The improved transfection efficiency was due to an enhanced DNA uptake by the skin cells. Gene transfer was most evident in the subdermal smooth muscle cells and epidermal cells. With the optimized conditions, gene transfer mediated by intradermal injection of naked DNA was comparable in efficiency to electroporation. However, cellular distributions of the gene transfer of the two methods were different. PMID- 11786047 TI - Sustained human factor VIII expression in hemophilia A mice following systemic delivery of a gutless adenoviral vector. AB - Gutless adenoviral vectors are devoid of all viral coding regions and display reduced cytotoxicity, diminished immunogenicity, and an increased coding capacity compared with early generation vectors. Using hemophilia A, a deficiency in clotting factor VIII (FVIII), as a model disease, we generated and evaluated a gutless vector encoding human FVIII. The FVIII gutless vector grew to high titer and was reproducibly scaled-up from vector seed lots. Extensive viral DNA analyses revealed no rearrangements of the vector genome. A quantitative PCR assay demonstrated helper virus contamination levels of <2%, with the best preparation containing 0.3% helper virus. We compared the gutless vector with an E1/E2a/E3-deficient (Av3) early generation vector encoding an identical FVIII expression cassette following intravenous administration to hemophilia A mice. Gutless vector-treated mice displayed 10-fold higher FVIII expression levels that were sustained for at least 9 months. In contrast, mice treated with the Av3 vector displayed FVIII levels below the limit of sensitivity of the assay at 3 months. Assessment of hepatotoxicity by measuring the serum levels of liver enzymes demonstrated that the gutless vector was significantly less toxic than the Av3 vector at time points later than 7 days. At the highest dose used, both vectors caused a transient 10-fold increase in liver enzymes 1 day after vector administration, suggesting that this increase was caused by direct toxicity of the input capsid proteins. These data demonstrate that the gutless vector displayed increased duration and levels of FVIII expression, and was significantly less toxic than an analogous early generation vector. PMID- 11786048 TI - Expression of a beta-adrenergic receptor kinase inhibitor reverses dysfunction in failing cardiomyocytes. AB - The spontaneously hypertensive heart failure (SHHF) rat shares numerous functional and molecular characteristics of human heart failure (HF), including impairment of beta-adrenergic receptor (AR) signaling with decreased betaAR density and coupling to adenylyl cyclase as well as increased betaAR kinase (betaARK1) levels and activity. We examined the effects of betaARK1 inhibition on the signaling and contractile function in failing ventricular myocytes isolated from SHHF rat hearts. This was done by adenoviral-mediated gene transfer of the carboxy-terminal 194 amino acids of betaARK1 (betaARKct), which acts as an in vivo betaARK1 inhibitor. Basal cAMP production was reduced in cells from SHHF rat hearts (n=4) compared with that found in cells isolated from the hearts of age matched Sprague-Dawley (SD) control rats (n=8; SHHF, 2.5+/-0.2% conversion [(3)H]adenine to cAMP, versus SD, 4.2+/-0.2%; P<0.01), as were cAMP responses to the beta-agonist iso-proterenol (ISO; SHHF, 5.2+/-0.2%, versus SD, 7.2+/-0.4%; P<0.01). Following betaARKct expression, SHHF cardiomyocytes displayed a significant increase in basal (6.6+/-0.6%, P<0.01) and ISO-stimulated cAMP production (8.8+/-0.6%, P<0.01) versus failing myocytes treated with an empty adenovirus. Concerning contractile function of these cells, betaARKct expression produced significant improvement in ISO (10(-6) M) stimulated (n=7 hearts) cell shortening, relaxation, and contraction compared with failing cells treated with the control empty virus (betaARKct, 39+/-11%, 70+/-18%, and 70+/-20%, versus empty virus, 1+/-7%, 5+/-5%, and 0+/-7%, respectively). Thus, these data indicate that targeted betaARK1 inhibition via genetic manipulation is a powerful therapeutic approach for improving the function of failing cardiomyocytes. PMID- 11786049 TI - Overcoming the nuclear barrier: cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation. AB - In many cases, nonviral particle-mediated gene delivery is highly dependent on the cell cycle status of transfected cells. Here we compare particle-mediated delivery with linear polyethylenimine (PEI) and physical transfer of DNA by electroporation with branched PEI and lipofection for their ability to transfect cells at different stages of the cell cycle. In contrast to other particle mediated delivery methods (using Lipofectamine or branched PEI) linear PEI led to only small differences (within 1 log unit) in gene transfer between HeLa cells transfected in G1 and those in S/G2. Parallel transfections (lipofection or branched PEI) resulted in 2 to > 3 log-unit differences in luciferase expression between cells transfected in G1 and S/G2. Gene transfer by electroporation also revealed hardly any cell cycle dependence and displayed completely different expression kinetics. Reporter gene expression is already very high 3 hours after electroporation with roughly the same level of reporter gene expression in all cell cycle phases. We suggest that DNA electroporation and DNA transfection with linear PEI particles have improved nuclear import characteristics relative to the other tested DNA delivery systems. PMID- 11786050 TI - Improvement in adenoviral gene transfer efficiency after preincubation at +37 degrees C in vitro and in vivo. AB - Adenovirus is a widely used vector in gene transfer experiments because it produces high transduction efficiency in vitro and in vivo by means of the coxsackie-adenovirus receptor (CAR) and major histocompatibility complex (MHC) class I alpha-2 domain. Adenoviral gene transfer efficiency has been reported to correlate with cellular CAR expression. We report here a simple method to increase adenoviral gene transfer efficiency in cells that do not express high levels of CAR: preincubation of adenovirus for 30-40 minutes at +37 degrees C significantly increased the transduction efficiency in vitro in CHO and BALB/3T3 cells, in which CAR is expressed at very low levels. Increased transduction efficiency of preincubated adenovirus was also detected in vivo in rat brain tissue. In addition, we found that adenoviruses were rapidly inactivated in human serum in a complement-independent manner, whereas fetal bovine serum (FBS) had hardly any effects on the viral infectivity. We conclude that preincubation of adenoviral vectors at +37 degrees C may substantially increase gene transfer efficiency in applications in which target cells do not express high levels of CAR. PMID- 11786052 TI - Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. AB - OBJECTIVES: To evaluate ocular characteristics and systemic disease associations in patients with scleritis-associated peripheral keratopathy and its different patterns, and to assess any ocular or systemic prognostic significance of the presence of the types of peripheral keratopathy in patients with scleritis. DESIGN: Review of 125 patients with scleritis alone and 47 patients with scleritis-associated peripheral keratopathy; review of patients with scleritis and the different patterns of peripheral keratopathy: peripheral corneal thinning, stromal keratitis, and peripheral ulcerative keratitis (PUK); review of ocular and systemic outcomes comparisons between patients with scleritis with and without peripheral keratopathy. RESULTS: Patients with peripheral keratopathy had more necrotizing scleritis (57%, P<.001), decrease in vision (81%, P<.001), anterior uveitis (62%, P<.002), impending corneal perforation (62%, P<.001), and potentially lethal specific-disease association (87%, P<.001) than did patients with scleritis alone. Patients with PUK had the worst ocular and systemic outcomes. Of the 24 patients with PUK, 16 (67%) had necrotizing scleritis (P =.02), virtually all had a potentially lethal systemic disease (P =.02), and all had impending corneal perforation (P<.001). CONCLUSION: The detection of peripheral keratopathy, and especially PUK, in a patient with scleritis indicates a poor ocular and systemic prognosis. PMID- 11786053 TI - Quantitative performance of bifocal and multifocal intraocular lenses in a model eye: point spread function in multifocal intraocular lenses. AB - OBJECTIVE: To compare the optical properties of bifocal diffractive and multifocal refractive intraocular lenses. METHODS: A model eye with a pupil 4.5 mm in diameter was used to determine the point spread function (PSF) of the distance focus and near focus of a diffractive bifocal intraocular lens (IOL) (model 811E; Pharmacia Inc, Columbus, Ohio) and of a refractive multifocal IOL (model SA40N; Allergan Optical Inc, Irvine, Calif) to compare them with PSFs of foci of corresponding monofocal lenses. For interpreting the PSFs the through focus response, the modulation transfer function, and the Strehl ratio were evaluated. RESULTS: The intensity of the distance focus of the bifocal diffractive lens reached 58.5% and the near focus attained 42.7% of the intensity of a corresponding monofocal lens. The maximal halo intensity surrounding both foci was approximately 4.5%. The distance peak of the refractive multifocal IOL was 73.4% and the near peak 25.1% of a corresponding monofocal lens. The out-of focus image overlaying the distance focus of the refractive multifocal IOL was approximately 3% of the light intensity of the distance focus, whereas the PSF of the near focus of the multifocal IOL is substantially affected by out-of-focus images. The computed modulation transfer functions show better results for the monofocal lenses, similar results for the tested distance foci, and clear advantages for the bifocal diffractive near focus. CONCLUSIONS: Modulation transfer functions reveal comparable properties for distance vision and a superiority of the bifocal diffractive lens over the refractive multifocal lens for near vision. PMID- 11786054 TI - Anatomical outcomes of surgery for idiopathic macular hole as determined by optical coherence tomography. AB - OBJECTIVES: To determine the rate of anatomical closure of idiopathic macular holes undergoing vitreous surgery with respect to preoperative horizontal diameter as determined by optical coherence tomography (OCT) and to correlate postoperative visual acuity, duration of symptoms, and late reopening with initial idiopathic macular hole diameter by OCT. MATERIALS AND METHODS: Forty eyes of 40 patients with an idiopathic macular hole were examined with OCT before and after vitreous surgery. All eyes were treated with pars plana vitrectomy, peeling of posterior cortical vitreous, and dilute perfluoropropane or sulfur hexafluoride gas. Face-down positioning was maintained for 7 to 14 days. RESULTS: Twenty-two (92%) of 24 eyes with a preoperative idiopathic macular hole diameter smaller than 400 microm measured by OCT attained anatomical closure following surgery. Anatomical closure was observed in 9 (56%) of 16 eyes with a macular hole diameter of 400 microm or larger measured by OCT (P =.02). The median postoperative visual acuity improvement was 4 Snellen lines in the 31 eyes achieving anatomical closure and no change in the 9 eyes not achieving anatomical closure (P< .001). Late macular hole reopening at longer than 6 months occurred in 3 (10%) of 31 eyes with an initially closed macular hole. This event was observed only in macular holes 400 microm or larger measured by OCT. The preoperative macular hole diameter (P =.02) and duration of symptoms (P =.02) were factors predictive of anatomical closure of the macular hole postoperatively. CONCLUSIONS: The postoperative closure of idiopathic macular holes following vitreous surgery was related to the preoperative macular hole diameter determined by OCT, with lesions smaller than 400 microm demonstrating higher success rates. A trend toward greater visual acuity improvement was demonstrated for idiopathic macular holes smaller than 400 microm. Late reopening was only seen in macular holes that were 400 microm or larger measured by OCT. Preoperative analysis and measurement of idiopathic macular holes with OCT may help delineate postoperative expectations for successful anatomical closure of the macular hole, visual acuity, and long-term closure. PMID- 11786055 TI - Leopard-spot pattern of yellowish subretinal deposits in central serous chorioretinopathy. AB - OBJECTIVE: To describe clinical and angiographic features of patients with central serous chorioretinopathy (CSC) who had yellowish subretinal deposits forming a reticulated leopard-spot pattern during fluorescein angiography. METHODS: We conducted case studies using the clinical and photographic records of 5 patients. RESULTS: All 5 patients were older men between the ages of 68 and 81 years who had been treated with corticosteroids and had bilateral CSC. Nine eyes of the 5 patients developed yellowish deposits in a reticulated pattern in the macular region under the chronic detached neurosensory retina. The pattern of leopard-spot deposits was well demonstrated on the fluorescein angiogram, with hypofluorescence in most of the deposits and hyperfluorescence from atrophy of the retinal pigment epithelium. Later phases of the fluorescein angiographic study showed leaks from the retinal pigment epithelium. During the indocyanine green angiography evaluation of 4 patients, all had bilateral multifocal patches of hyperfluorescence in the midphase, findings typical of CSC. CONCLUSIONS: Yellowish deposits forming a reticulated leopard-spot pattern may occur under the neurosensory retina and are associated with chronic neurosensory detachment caused by CSC. All patients were older men being treated with corticosteroids. This report described a newly recognized finding: the subretinal deposition of a yellowish material in a leopard-spot pattern in eyes with CSC. PMID- 11786056 TI - Electronegative electroretinogram in mucolipidosis IV. AB - OBJECTIVE: To demonstrate the progression of electroretinographic (ERG) findings in mucolipidosis IV. METHODS: Two patients with mucolipidosis IV were examined clinically and their condition was followed up for ophthalmic manifestations of the disease. Electroretinograms were performed on both patients, and conjunctival biopsy specimens were analyzed for characteristic ultrastructural inclusion bodies using light and electron microscopy. Genomic DNA isolated from peripheral blood was screened for 2 major founder mutations in the ML4 gene using polymerase chain reaction and restriction fragment length polymorphism analyses. Haplotypes were confirmed by automated sequencing of polymerase chain reaction products. RESULTS: In patient 1, an ERG obtained at 12 months of age showed mildly subnormal amplitude of rod-mediated and cone-mediated responses and significantly prolonged rod and cone b-wave implicit times. An ERG obtained when the patient was 6.6 years old disclosed marked progression with greater loss of b-wave than a wave responses to rod-and-cone-mediated activity. Scotopic ERG at the highest intensity was electronegative in configuration. In patient 2, ERG showed minimal rod-mediated responses, severely subnormal cone-mediated responses, and prolonged cone b-wave implicit times. Again, electronegative configuration of the scotopic bright flash response indicated greater disturbance of b-wave generators. CONCLUSIONS: Novel ERG findings in 2 cases of mucolipidosis IV are reported with associated clinical courses, histopathologic abnormality, and genetic studies. In both cases ERGs demonstrate an electronegative configuration, suggesting that the primary retinal disturbance in mucolipidosis IV may occur at or proximal to the photoreceptor terminals. PMID- 11786057 TI - Topical diclofenac sodium decreases the substance P content of tears. AB - OBJECTIVE: To explore the mechanism by which diclofenac sodium eyedrops exert an adverse effect on the cornea. METHODS: In 10 healthy Japanese volunteers, 0.1% diclofenac sodium solution was instilled into one eye 3 times daily for 2 weeks. Only vehicle was applied to the other eye. Tear samples were taken before drug treatment, at 2 weeks (on the final day of treatment), and at 4 weeks. Prostaglandin E(2) and substance P concentrations in tears were measured using enzyme immunoassays. RESULTS: After treatment for 2 weeks, concentrations of both prostaglandin E(2) and substance P in tears from diclofenac sodium-treated eyes had decreased significantly, and both had returned to baseline levels by 4 weeks. No significant changes were seen in prostaglandin E(2) and substance P levels in vehicle-treated eyes at any time points. CONCLUSIONS: Diclofenac sodium eyedrops concurrently reduced concentrations of prostaglandin E(2) and substance P in tears. Depletion of substance P (a pain-associated neurotransmitter) by diclofenac sodium may promote development of corneal complications. PMID- 11786058 TI - Clinical course and visual function in a family with mutations in the RPE65 gene. AB - OBJECTIVE: To evaluate the phenotype of affected and carrier members of a family with mutations in RPE65 (a retinal pigment epithelium gene). METHODS: RPE65 mutation screening was performed on DNA from 2 affected brothers, 1 unaffected brother, both parents, and 3 surviving grandparents using cycle sequencing. Ophthalmic examinations included ophthalmoscopic fundus examination; visual function testing; 2-color, static, dark-adapted threshold perimetry; and rod electroretinographic a-wave phototransduction analysis. RESULTS: The 2 affected brothers carried RPE65 mutations in compound heterozygous form: a maternal Y368H (1156T-->C) missense mutation and a paternal IVS1 + 5g-->a splice-site mutation. Severe visual deficits and an absence of rod and cone electroretinographic responses were diagnosed in both affected boys before the age of 5 years. Visual acuities of about 20/100 during grade school declined to hand movements by the teenage years, and only a rudimentary peripheral temporal visual field remained by the ages of 25 and 29 years. Both parents had normal central visual function, as measured by visual acuity, contrast sensitivity, color vision, and Humphrey 10 2 fields. However, the 50-year-old father showed hundreds of tiny whitish hard drusen in both eyes and had abnormal peripheral function on dark-adapted perimetry, with extended field defects of 15 to 20 dB outside 30 degrees eccentricity. His rod photoreceptor sensitivity and amplitude, calculated by fitting the rod a waves by a model of activation of phototransduction, were normal, but the flicker electroretinographic response was delayed. CONCLUSIONS: The RPE65 mutations Y368H and IVS1 + 5g-->a present in compound heterozygous form cause severe visual compromise in childhood and progress to nearly total vision loss by the second to third decades of life. The retinal and functional changes in the father carrying a presumed functional null allele suggest that some RPE65 heterozygous carriers may manifest visual symptoms. PMID- 11786059 TI - Presbyopia's finest hour. PMID- 11786060 TI - Glaucoma surgery and aqueous outflow: how does nonpenetrating glaucoma surgery work? PMID- 11786061 TI - Ethics of comanagement. PMID- 11786062 TI - Mitochondria-rich epithelioid leiomyoma of the ciliary body. PMID- 11786063 TI - Mushroom-shaped choroidal melanocytoma mimicking malignant melanoma. PMID- 11786064 TI - Intravitreal hemoglobin spherulosis: a rare complication of subretinal hemorrhage. PMID- 11786065 TI - Pseudohypopyon as a feature of multiple myeloma. PMID- 11786066 TI - Anterior uveitis after healed acute retinal necrosis. PMID- 11786067 TI - Pseudomonas aeruginosa-related postoperative endophthalmitis linked to a contaminated phacoemulsifier. PMID- 11786068 TI - Intraocular hemorrhages due to warfarin fluconazole drug interaction in a patient with presumed Candida endophthalmitis. PMID- 11786069 TI - Adult-onset limbal juvenile xanthogranuloma. PMID- 11786070 TI - Brain necrosis after enucleation, external beam cobalt radiotherapy, and systemic chemotherapy for retinoblastoma. PMID- 11786071 TI - AREDS investigators distort findings. PMID- 11786073 TI - Epithelial origin of "stromal" corneal dystrophies. PMID- 11786075 TI - Corneal thickness factors and intraocular pressure. PMID- 11786077 TI - Treating subretinal hemorrhage with tissue plasminogen activator. PMID- 11786079 TI - Immunoglobulin light chain amyloidosis and the kidney. AB - Immunoglobulin light chain amyloidosis and the kidney. Amyloidosis (AL) is a common cause of nephrotic syndrome in nondiabetic, nonhypertensive adults. All adult patients with nephrotic syndrome should have immunofixation of serum and urine as a screen. The finding of a monoclonal protein, particularly of lambda type, should lead to a subcutaneous fat aspirate or bone marrow biopsy to search for amyloid deposits. When the result of either test is positive, a kidney biopsy is unnecessary. The prognosis of patients who have renal amyloidosis depends on the concentration of serum creatinine at presentation and whether an echocardiographic evaluation demonstrates infiltrative cardiomyopathy. Most therapies are directed against the plasma cell dyscrasia present in all patients with AL and can include melphalan and prednisone, high-dose dexamethasone, and, most recently, peripheral blood stem cell transplantation. PMID- 11786080 TI - Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. AB - Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. There are a large number of developmental disorders and syndromes that affect the kidney and upper urinary tract. These have generally been classified according to morphological criteria established decades ago. Although these classifications have been useful, they are incomplete, including some developmental disorders while excluding others. Here, basic cellular and molecular biology studies of kidney and upper urinary tract development in both rodents and humans are utilized to suggest the basis of a new etiologic, if still tentative, classification scheme. This classification may help to identify candidate genes for human diseases by correlating morphology with pathogenetic mechanisms. PMID- 11786081 TI - Cytokine-induced expression of tPA is differentially modulated by NO and ROS in rat mesangial cells. AB - BACKGROUND: Dysregulated expression of diverse proteases and their specific inhibitors is critical for the increase in extracellular matrix accumulation that accompanies chronic inflammatory and sclerotic processes within the renal mesangium. Within the activating cascade of several proteases, the plasminogen system plays an important role. METHODS: We tested for modulatory effects of the nitric oxide (NO) donors S-nitroso-N-acetyl-D,L-penicillamine and DETA-NONOate, and the superoxide-generating system hypoxanthine/xanthine oxidase (HXXO) on the expression and activity of tissue plasminogen activator (tPA) by ELISA and Northern blotting. RESULTS: Interleukin-1beta (IL-1beta)-induced tPA and plasminogen activator inhibitor (PAI)-1 mRNA and supernatant tPA antigen were significantly inhibited by both NO donors, which resulted in a net decrease in the IL-1beta-evoked tPA enzyme activity in the conditioned media. Addition of the NO-synthase inhibitor N-monomethyl l-arginine markedly increased the cytokine triggered tPA- and PAI-1 mRNA levels, respectively. In contrast, HXXO caused a marked amplification of the IL-1beta-induced steady-state tPA mRNA level and tPA enzyme activity that was blocked by catalase. Since MnTBAP, a superoxide dismutase mimetic, had no effects on the amplification of mRNA levels, we suggest that H2O2 is the candidate reactive oxygen species (ROS) responsible for the potentiation of IL-1beta-triggered tPA and PAI-1 expression. CONCLUSIONS: The temporal relationship between NO and ROS generation is a critical step in the modulation of tPA and PAI-1 expression in mesangial cells and may account for a dysregulation of matrix turnover during inflammatory processes in the renal mesangium. PMID- 11786082 TI - Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats. AB - BACKGROUND: Tubular atrophy is a major feature of most renal diseases and is closely associated with loss of renal function. The present study sought to investigate tubular epithelial cell apoptosis in experimental diabetic nephropathy and to explore the role of pro-apoptotic [transforming growth factor beta (TGF-beta) and anti-apoptotic growth factors [epidermal growth factor (EGF)]. The effects of renoprotective therapy with blockade of the renin angiotensin system (RAS) also were examined. METHODS: Six-week-old female Ren-2 rats were injected with streptozotocin (STZ) and maintained diabetic for 12 weeks. Further groups of diabetic rats were treated with the angiotensin converting enzyme (ACE) inhibitor, perindopril, or the angiotensin II type 1 (AT1) receptor antagonist, valsartan, for 12 weeks. RESULTS: Widespread apoptosis, identified immunohistochemically by single stranded DNA and TUNEL, was noted in the tubules of diabetic Ren-2 rats. These changes were associated with a 50% decrease in EGF expression and a twofold increase in TGF-beta1 mRNA. Treatment of diabetic Ren-2 rats with either valsartan (20 mg/kg/day) or perindopril (6 mg/kg/day) reduced apoptosis to control levels in association with supranormal levels of EGF mRNA (P < 0.01) and a reduction in TGF-beta1 gene expression (P < 0.05) to that of control rats. CONCLUSIONS: Tubular apoptosis is a prominent feature of diabetic Ren-2 rats that is attenuated by blockade of the RAS in association with modulation of pro- and anti-apoptotic growth factor expression. PMID- 11786083 TI - Mechanical stress reduces podocyte proliferation in vitro. AB - BACKGROUND: Mechanical stretch, a consequence of capillary glomerular hypertension, is thought to be the common final pathway for glomerulosclerosis in systemic hypertension, diabetes, reduced nephron number and focal segmental glomerulosclerosis. However, the effects of stretch on podocyte growth and the mechanisms that underlie this have not been elucidated. METHODS: Mouse podocyte growth (3H-thymidine, MTT-assay, FACS) was measured following the application of mechanical stretch created by vacuum. The expression of specific cell cycle regulatory proteins was examined by RNAse protection assay and Western blot analysis. Control cells were grown under similar conditions, but were not exposed to stretch. RESULTS: Mechanical stretch decreased DNA-synthesis (3H-thymidine incorporation) and cell number (MTT-assay) in podocytes at 24, 48 and 72 hours (P < 0.001 vs. control non-stretched cells), which was not due to apoptosis (Hoechst staining) nor cell detachment. Stretch decreased the mRNA and protein levels of cyclins D1, A and B1 within 24 hours. Stretching cells decreased the activity of Cdk2 (measured by histone H1 kinase assay) at 48 and 72 hours and Cdc2 at 72 hours. In contrast, stretch increased the protein levels of the cyclin dependent kinase inhibitors (CKI) p21Cip/Kip/Waf (p21) and p27Kip1 (p27) within the first 24 hours, and increased the mRNA levels of p57Kip2 (p57) at 72 hours. To examine the role of p21 in inhibiting proliferation induced by stretch, we studied p21-/- podocytes in culture. Stretch did not reduce proliferation in p21-/- podocytes (P> 0.05 vs. non-stretched podocytes; P < 0.001 vs. stretched p21+/+ podocytes). CONCLUSIONS: In contrast to mesangial cells, mechanical stretch decreases the growth of podocytes. This effect is mediated through the regulation of specific cell cycle regulatory proteins. These events may explain the apparent lack of podocyte proliferation in diseases correlated with capillary glomerular hypertension. PMID- 11786085 TI - Role of TGF-beta1 in renal parenchymal scarring following childhood urinary tract infection. AB - BACKGROUND: Significant variability exists in the outcome of renal parenchymal inflammation following urinary tract infection (UTI) in childhood as some children experience renal parenchymal scarring (RPS) while others do not scar. Since TGF-beta1 is pro-fibrotic, we examined the role of this cytokine in RPS following UTI. METHODS: Five polymorphisms of the TGF-beta1 gene were investigated as well as the relationship between these polymorphisms and TGF beta1 production by peripheral blood mononuclear cells (PBMC) in vitro. DNA was isolated from 91 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI, and 171 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP). PBMC were isolated from a subgroup of 24 patients from the total population. Cells were stimulated with LPS + PMA + PHA and then TGF-beta1 production was determined by ELISA. RESULTS: Comparing the NS with the RPS group, there was an increase in the -800 GA genotypes (18.6 vs. 7.4%, P=0.05; chi2) and the Leu10-->Pro CT (62.8 vs. 41.5%, P=0.021), and a decrease in the -509 TT genotype (0.0 vs. 8.5%, P=0.049). PBMC TGF-beta1 production was higher in those patients with the -800 GG compared to those with a GA genotype stimulation index [stimulated/unstimulated TGF-beta1 levels were 1.54 interquartile range (IQR) 1.42 to 1.75 vs. 1.19, IQR 0.94 to 1.51, P=0.031]. CONCLUSIONS: There is an association between the TGF-beta1 -800 GA, -509 TT and Leu10-->Pro CT genotypes and the presence or absence of RPS. The low TGF-beta1 producer status of the -800 GA genotype may protect against the development of a pro-fibrotic pathology. PMID- 11786084 TI - BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. AB - BACKGROUND: Proximal tubule epithelial cells (PTEC) play a central role in the response of the kidney to insult by virtue of their production of chemokines and cytokines that signal an inflammatory response. Bone morphogenic protein-7 (BMP 7/OP-1), a member of the transforming growth factor-beta (TGF-beta) superfamily, has previously been demonstrated to reduce macrophage infiltration and tissue damage in animal models of acute and chronic renal failure. The present study was designed to define the molecular mechanism of BMP-7 action in human PTEC. METHODS: Expression of BMP-7 in the adult mouse kidney was determined indirectly through X-gal staining of heterozygous BMP-7/lacZ mice in combination with cell type specific markers. Primary human PTEC were cultured in the presence of the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), with and without BMP-7. RNA isolated from these two populations was then used to identify differentially regulated genes via gene-array analysis. Modulation of potential target genes was subsequently confirmed through ELISA and/or quantitative PCR. RESULTS: Expression from the BMP-7/lacZ transgene was detected in the collecting duct, thick ascending limb, distal convoluted tubule, and podocytes within glomeruli. No expression was detected within PTEC; however, these cells were found to express mRNA for BMP receptors including, ActR-I, BMPR-IA, ActR-II, ActR IIB, and BMPR-II. BMP-7 significantly reduced TNF-alpha stimulated increases in mRNA for the pro-inflammatory genes, interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), and the chemoattractants monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in primary human PTEC. In addition, BMP-7 also reduced the expression of mRNA for endothelin-2 (ET-2), a vasoconstrictor, and increased the expression of mRNA for heme oxygenase-1 (HO-1), a vasodilator, although the latter was not statistically significant. In experiments designed to examine MCP 1 and IL-6 protein levels in response to additional TGF-beta superfamily members, TGF-beta1 was unable to mimic the effects of BMP-7 in reducing IL-6 production. However, the closely related BMP-6 exhibited similar properties to those of BMP 7. Each of the factors reduced MCP-1 expression. CONCLUSIONS: BMP-7 represses the basal and TNF-alpha-stimulated expression of the pro-inflammatory cytokines IL-6 and IL-1beta, the chemokines MCP-1 and IL-8, and the vasoconstrictor ET-2 in PTEC. This data are consistent with the in vivo observations that BMP-7 administration in a model of chronic and acute renal failure results in a reduction in the infiltration of macrophages in the renal interstitium. Taken together, these observations suggest that BMP-7 may be a novel therapeutic agent for kidney disorders involving inflammation and ischemic damage of PTEC. PMID- 11786086 TI - Induction of p27KIP1 after unilateral ureteral obstruction is independent of angiotensin II. AB - BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by proliferation of tubular and interstitial cells, and infiltration of the renal parenchyma with macrophages/monocytes. These alterations lead ultimately to tubulointerstitial fibrosis and tubular atrophy. Some of these changes are caused by an activated renin-angiotensin system (RAS). We have previously demonstrated that angiotensin II induces the expression of the cell cycle inhibitor p27KIP1 in cultured tubular cells. The current study tested the hypothesis that interference with the RAS may modulate renal expression of p27KIP1 after UUO. METHODS: The ureter of the left kidney of Sprague-Dawley rats was ligated. Sham-operated animals served as controls. Rats were randomized in four groups and received one of the following: no therapy, enalapril, losartan, or triple therapy (hydralazine, reserpine, hydrochlorothiazide). Kidneys were removed and cortical protein lysates were prepared for the detection of p27KIP1 by Western blotting. Immunohistochemistry was performed for p27KIP1, PCNA, ED-1, and alpha-smooth muscle actin. Apoptosis was quantified by TUNEL-staining. RESULTS: p27KIP1 expression as detected by Western blotting reached a maximum 10 days after UUO. Tubular and interstitial cells contributed to this increase in p27KIP1 expression whereas the number of glomerular p27KIP1 positive cell did not change. p27KIP1 positive cells were macrophages/monocytes (positive ED-1 staining) or had the characteristics of myofibroblasts (positive alpha-smooth muscle actin staining). Tubular and interstitial proliferation [proliferating cell nuclear antigen (PCNA) positive staining] and apoptosis [terminal deoxy transferase uridine triphosphate nick end labeling (TUNEL) staining] also was increased after UUO. However, individual cells stained either positive for p27KIP1 or PCNA, but not both. Although enalapril and losartan reduced the number of macrophages/monocytes and attenuated the degree of tubular and interstitial apoptosis, these drugs did not influence p27KIP1 expression. There was no change in the number of p27KIP1 positive cells in the contralateral kidney undergoing hypertrophy. CONCLUSION: Induction of p27KIP1 in this model represents an endogenous response to likely limit proliferation that is independent of angiotensin II. Since there was no close correlation between apoptosis and p27KIP1 expression, it may be that the overall number of p27KIP1 expressing cells sets a general restriction point for apoptosis rather than defines an individual level of cell fate. PMID- 11786087 TI - Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. AB - BACKGROUND: Differences in renal histopathology between microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG), and between anti-neutrophil cytoplasm autoantibody (ANCA) test results in patients with ANCA-associated vasculitis may provide insight into the differences in pathogenesis and raise the opportunity of classifying the vasculitides more accurately. The possible differences in histopathology are investigated in this study. METHODS: We report an analysis of 173 patients with renal disease in microscopic polyangiitis or Wegener's granulomatosis. A total of 173 renal biopsies, performed at diagnosis, were scored by two observers separately, using a previously standardized protocol. Consensus on each biopsy was achieved during a central review. RESULTS: Normal glomeruli were more common in WG than in MPA (P < 0.001). Glomerulosclerosis was more prominent in MPA than in WG (P=0.003). Interstitial fibrosis (P < 0.001), tubular atrophy (P < 0.001), and tubular casts (P=0.005) were more frequently present and more severe in MPA than in WG. Presence of glomerulosclerosis was more extensive in patients with myeloperoxidase (MPO)-ANCA than with proteinase 3 (PR3)-ANCA (P=0.022). Interstitial fibrosis (P=0.008), tubular necrosis (P=0.030), tubular atrophy (P=0.013), and intra-epithelial infiltrates (P=0.006) were more frequently present and more severe in MPO-ANCA than in PR3-ANCA. CONCLUSIONS: Glomerulonephritis in relation to MPA has more characteristics of chronic injury at the time of presentation than glomerulonephritis in relation to WG. This difference may be due to a delayed establishment of diagnosis in patients with MPA compared to patients with WG. Both active and chronic lesions are more abundantly present in MPO-ANCA-positive patients than in patients with PR3-ANCA-positivity, which suggests that the pathogenesis of renal disease in these ANCA subsets could be different. Our results also suggest that ANCA test results may be useful in classifying ANCA-associated vasculitides. PMID- 11786088 TI - Activated intrarenal transcription of CTL-effectors and TGF-beta1 in children with focal segmental glomerulosclerosis. AB - BACKGROUND: The pathogenesis of childhood nephrotic syndrome (NS), whether the lesion is minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), remains elusive. Based on the presence of elevated cytokine levels in peripheral blood, a T cell-induced injury could be postulated. METHODS: To test the hypothesis that infiltrating T cells actively contribute to the glomerular injury in children with NS, we studied the intrarenal transcription of various T cell-related chemokines, cytokines and cytotoxic T-lymphocyte (CTL) effector molecules in the renal biopsy tissue of 52 nephrotic children with a variety of histologic lesions. Intrarenal gene expression was studied using reverse transcription (RT)-assisted-polymerase chain reaction (PCR). RESULTS: Interleukin 2 (IL-2) and IL-4 transcripts were not observed in any of the specimens. IL-2 receptor alpha mRNA was detected in 24 of 40 proteinuric patients, but also in 6 of 10 patients in remission and showed no significant differences with regard to steroid response. Intrarenal gene expression of CTL mediators and transforming growth factor-beta1 (TGF-beta1) was noted particularly in patients with progressive disease leading to chronic renal failure. TGF-beta1 gene expression was noted in 23 of 29 steroid resistant (SR) children with NS not caused by lupus nephritis and in 18 of 20 FSGS patients. In contrast TGF-beta1 gene expression was detected in only 3 of 14 steroid-sensitive patients (P < 0.001). Two of these patients later developed FSGS. In patients with steroid-resistant NS, intrarenal TGF-beta1 gene expression showed a positive predictive value of 90% and a negative predictive value of 88% to identify FSGS (P < 0.0001). CONCLUSION: These results support the notion that immunologically mediated events contribute to the progressive renal damage seen in children with FSGS. PMID- 11786089 TI - Protective effects of a soy diet in preventing obesity-linked renal disease. AB - BACKGROUND: Hypertension, hyperlipidemia, hyperfiltration, hyperinsulinemia, glomerular hypertrophy, and ultimately glomerular injury and renal failure are associated with obesity in the Zucker rat. Evidence from other laboratories suggests that soy protein might offer renal protection. METHODS: At five weeks of age obese rats were placed on diets containing either soy or casein as a protein source and studied until 24 weeks of age. At six weeks of age and every four weeks thereafter, 24-hour urine collections were obtained along with measurements of systolic blood pressure (tail cuff) and blood from the tail vein. At the end of the study the kidneys were fixed and sectioned for histology. RESULTS: Both groups gained weight and developed systemic hypertension and hyperinsulinemia at the same rate. Glomerular filtration rate (creatinine clearance) also was similar between groups throughout the study and both groups developed glomerular hypertrophy to the same extent. The development of hypertriglyceridemia was actually accelerated in the soy-fed rats compared to the casein-fed animals. The soy diet, however, virtually completely prevented the development of hypercholesterolemia, primarily low-density lipoprotein (LDL) and/or very low density lipoprotein (VLDL) cholesterol, and slowed the development of proteinuria and glomerular injury. CONCLUSIONS: The data suggest that an important determinant of the protective effects of soy was related to the prevention of hypercholesterolemia in this model. Other unmeasured differences between groups, such as differences in glomerular capillary blood pressure or the effects of the antioxidant properties of soy components also may have contributed to the protective effects of soy. PMID- 11786090 TI - Oxalate ions and calcium oxalate crystals stimulate MCP-1 expression by renal epithelial cells. AB - BACKGROUND: Crystals of calcium oxalate monohydrate (COM) and excess oxalate ions (OX) stimulate an array of responses inducing localized injury and inflammation in the kidneys. These inflammatory responses are key regulators of development of nephrolithiasis. We propose that monocyte chemoattractant protein-1 (MCP-1), a chemokine with potent chemotactic activity for monocytes/macrophages, is a mediator of local inflammatory responses to COM and OX-induced injury. To test this hypothesis, the effects of COM and OX on the expression of MCP-1 mRNA and protein by NRK52E rat renal tubular cells were investigated. METHODS: Confluent cultures of NRK52E cells were exposed to COM (33 to 267 microg/cm2) or OX (125 to 1000 micromol/L, estimated free oxalate levels of 65.8 to 540 micromol/L) and catalase (400 or 2000 U/mL), a free radical scavenger that protects the cells against detrimental effects of COM and OX, for 1 to 48 hours under serum free conditions. The conditioned media were collected and total cellular RNA isolated from the cells and subjected to enzyme-linked immunosorbent assay (ELISA) and semiquantitative polymerase chain reaction (PCR) to determine the expression of MCP-1 protein and mRNA, respectively. RESULTS: NRK52E cells express MCP-1 mRNA and protein, and the level of their expression significantly increases following treatments with COM and OX in a time and concentration dependent manner. MCP-1 mRNA expression and protein production increased more significantly after exposure to COM than to OX. These responses were significantly reduced following treatments with catalase (2000 U/mL). CONCLUSIONS: NRK52E cells express MCP-1 mRNA and protein, and their levels are altered following COM and OX exposure. Since catalase treatment reduced MCP-1 expression, free radicals may be involved in the up-regulation of MCP-1 production by the epithelial cells. The results suggest that elevated expression of MCP-1, which is often associated with local inflammatory response, may mediate similar reactions including attraction of macrophages seen around the interstitial crystals during the early stages of nephrolithiasis. PMID- 11786091 TI - Response of mesangial cells to low-density lipoprotein and angiotensin II in diabetic (OLETF) rats. AB - BACKGROUND: Progression of diabetic nephropathy is closely associated with morphological changes in glomeruli, such as thickening of the glomerular basement membrane, mesangial expansion, and glomerulosclerosis. To elucidate early glomerular events, we compared the mitogenic activity and extracellular matrix production in mesangial cells (MC) isolated from diabetic rats prior to the manifestation of nephropathy and those showing overt nephropathy. This study may help to clarify the mechanisms underlying diabetic nephropathy and provide clues about early therapeutic interventions for preventing or slowing this process. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a chronic model for human type 2 diabetes mellitus, and age-matched control (LETO) rats were used. Glomerular cell numbers, expression of immediate early genes (c-Fos and c-Myc) and proliferating cell nuclear antigen (PCNA), and low-density lipoprotein (LDL) deposition were determined in renal tissue sections from rats aged 15 to 75 weeks. Mesangial cells (MCs) from OLETF rats at two different stages of the disease, that is, young (12- to 14-week-old) OLETF rats (y-OLETF) prior to the manifestation of nephropathy and old (48- to 50-week-old) OLETF rats (o-OLETF) showing nephropathy, were isolated and cultured. After stimulation with native (n ) or oxidized (ox-) LDL or angiotensin II (Ang II), DNA synthesis and extracellular matrix (ECM) production were examined. Cellular expression of LDL/scavenger receptors was analyzed using fluorescence-labeled LDL and binding to 125I-labeled-LDL. RESULTS: The number of cells per glomerular cross section was significantly higher in OLETF rats than in LETO rats between 25 and 65 weeks of age. In OLETF glomeruli, c-Fos, c-Myc, and PCNA were transiently expressed in the early phase. Glomerular LDL deposition increased with the age of OLETF rats. Addition of a low dose of n-LDL (10 microg/mL) to the culture medium significantly stimulated DNA synthesis of y-OLETF MCs, as compared with o-OLETF MCs and LETO MCs (P < 0.05). A high dose of n-LDL (100 microg/mL) caused cytotoxic effects in all cells. Exposure to ox-LDL minimally affected DNA synthesis of OLETF or LETO MCs. LDL receptors and scavenger receptors were predominant in y-OLETF and o-OLETF, respectively. After stimulation with n-LDL and ox-LDL, expression of type I and type III collagen, along with transforming growth factor-beta (TGF-beta), was higher in o-OLETF MCs that in y-OLETF MCs or LETO MCs. Exposure to Ang II markedly induced DNA synthesis and ECM mRNA expression in y-OLETF MCs and o-OLETF MCs, respectively. CONCLUSIONS: These findings indicate that the cell proliferation process precedes the evolution of diabetic glomerulopathy. The responses of OLETF MCs to n-LDL/ox-LDL and Ang II differed depending on the stage of diabetes. In the early phase, MCs were prone to proliferate, whereas in the late stage, MCs, which expressed higher levels of TGF-beta, tended to synthesize ECM. A functional switch in MCs may contribute to the development of glomerulosclerosis in diabetic nephropathy. PMID- 11786092 TI - Laser microdissection and gene expression analysis on formaldehyde-fixed archival tissue. AB - BACKGROUND: Analysis of renal biopsies is currently based on histological recognition of typical structural patterns and immunohistological detection of protein expression alterations. Both can be performed using formaldehyde as the tissue fixative. As a consequence of recent advances in molecular medicine, mRNA expression analysis may offer an attractive option to obtain functionally relevant information. However, quantification of mRNA expression in human renal biopsies thus far has not been possible in formaldehyde-fixed tissue. METHODS: The present study evaluated a recently reported mRNA extraction protocol. Using this approach gene expression analysis could be performed on formaldehyde-fixed archival renal tissues by laser microbeam microdissection, laser pressure catapulting and real time reverse transcription-polymerase chain reaction. RESULTS: For an initial feasibility study, the expression of two chemokines (IP 10 and RANTES) in renal transplant rejection was examined. Induction of protein expression in allografts undergoing rejection was demonstrated for both chemokines by immunohistochemistry. The mRNA expression alterations in the defined renal compartments of glomeruli, vessels and tubulointerstitium were quantified using laser microdissection from formaldehyde-fixed, paraffin-embedded or frozen tissue sections. A pronounced increase of mRNA expression compared to controls was demonstrated for IP-10 as well as RANTES with both tissue-processing protocols. CONCLUSIONS: Using formaldehyde as the tissue fixative, information on the disease process can now be obtained by histological, immunohistochemical and gene expression techniques. In the future this may allow the study of activated molecular programs in routine renal biopsies as well as archival tissue samples. PMID- 11786093 TI - Quantitative gene expression analysis in renal biopsies: a novel protocol for a high-throughput multicenter application. AB - BACKGROUND: Recent advances in gene expression analysis may add the quantification of mRNA species in renal biopsies to routine diagnostic procedures in nephrology. METHODS: A systematic evaluation was performed on the relevant steps required to efficiently obtain cDNA from renal biopsies for high-throughput reverse transcription-polymerase chain reaction (RT-PCR) based mRNA quantification. RESULTS: The protocol preserves mRNA integrity by a novel RNase inhibitor and allows meticulous microdissection followed by maximal RNA recovery from tissue samples. Reverse transcription was optimized to give the best yield from minimal starting material. RNA quantity and quality were systematically investigated by real-time RT-PCR and electrophoresis on a microfluidic system, respectively. The reported procedure offers high RNA preservation and increases the yield of cDNA significantly compared to former protocols. CONCLUSION: The simplicity of biopsy material acquisition combined with the centrally performed processing makes this protocol suitable for a wide spectrum of expression analysis in diverse clinical settings. PMID- 11786094 TI - Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases. AB - BACKGROUND: Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier. METHODS: Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria associated protein expression was developed in various diagnostic groups of human kidney biopsies. RESULTS: In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down regulation in nephrin expression pattern was shown. CONCLUSIONS: Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place. PMID- 11786095 TI - AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. AB - BACKGROUND: Excess advanced glycation end-products (AGEs) are formed during renal failure, and AGE formation also may be connected with the high glucose concentration of peritoneal dialysis (PD) fluids. To determine the effect of human peritoneal mesothelial cell (HPMC) exposure to glycated proteins, we studied the HPMC receptor of AGE expression (RAGE), and analyzed the results of AGE-RAGE interaction on adhesion molecule expression and leukocyte binding. METHODS: RAGE was detected by FACS analysis, and RAGE mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Vascular and intercellular cell adhesion molecule (VCAM-1 and ICAM-1) expression was measured by a known radiometric technique under basal conditions, after the addition of an AGE specific compound, Nepsilon-carboxylmethyllysine (CML-albumin). Leukocyte adhesion on HPMC was analyzed by videomicroscopy after HPMC stimulation. RESULTS: RAGE protein was detected on HPMC, and RAGE mRNA was evidenced by RT-PCR. VCAM-1 expression was stimulated by CML-albumin (P < 0.01), while ICAM-1 was unchanged. By blocking the AGE-RAGE interaction, anti-RAGE antibodies or recombinant RAGE inhibited the increase in VCAM-1 expression. CML-albumin stimulation potentiated leukocyte adhesion to HPMC (P < 0.001). This effect was prevented by the incubation of leukocytes with recombinant VCAM-1 (P < 0.001). CONCLUSIONS: AGE binding to RAGE stimulated mesothelial cell activity, and resulted in the overexpression of VCAM-1, a structure for leukocyte adhesion. The AGE-RAGE interaction resulted in HPMC activation, which may promote local inflammation, and thus is implicated in the peritoneal injury found in long-term PD patients. PMID- 11786096 TI - Down-regulation of lipoprotein lipase and VLDL receptor in rats with focal glomerulosclerosis. AB - BACKGROUND: Patients and animals with nephrotic syndrome and those with chronic renal failure (CRF) often exhibit hypertriglyceridemia and impaired very low density lipoprotein (VLDL) clearance. Imai rats that were originally derived from Sprague-Dawley rats develop spontaneous proteinuria, hyperlipidemia, progressive renal insufficiency and histologic changes of focal glomerulosclerosis (FGS), closely resembling human FGS. This study was undertaken to test the hypothesis that elevation of plasma triglyceride and VLDL concentrations in the Imai rats is associated with deficiency of lipoprotein lipase (LPL) and VLDL receptor which are the main pathways of triglyceride-rich lipoprotein clearance. METHODS: Male Imai and Sprague-Dawley control rats were fed regular rat chow and studied at 10 and 34 weeks of age. Tissue LPL and VLDL-r protein abundance (Western analysis) and post-heparin lipolytic activity were determined. RESULTS: At 10 weeks of age, Imai rats showed mild proteinuria, moderate hyperlipidemia, normal creatinine clearance and blood pressure. By 34 weeks of age, the study animal exhibited severe proteinuria, marked hyperlipidemia, significant renal insufficiency and hypertension. This was associated with a severe progressive reduction in skeletal muscle and adipose tissue LPL and VLDL-r protein abundance and depressed plasma post heparin, lipolytic activity. CONCLUSION: Progressive hyperlipidemia in the Imai rats with spontaneous FGS is accompanied by severe combined LPL and VLDL-r deficiencies that can, in part, account for the associated hypertriglyceridemia and elevated plasma VLDL concentrations. PMID- 11786097 TI - Diurnal variations of glomerular filtration rate and albuminuria in diabetic nephropathy. AB - BACKGROUND: The aim of our study was to evaluate the diurnal variation in glomerular filtration rate (GFR), and the potential mechanisms responsible for such variations in GFR and albuminuria in diabetic nephropathy. METHODS: In three 24-hour urine samples, divided into a night- and daytime portion, diurnal variation in albuminuria (ELISA) was assessed. Furthermore, during recumbency changes in albuminuria, GFR (51Cr-EDTA plasma clearance) and arterial blood pressure (TM2420) from nighttime (00:00 to 05:00 hours) to subsequent daytime (08:00 to 13:00 hours) were examined in 20 type 1 diabetic patients with diabetic nephropathy. RESULTS: The 24-hour urine collections showed an average rise in albuminuria from night- to daytime of 51% (95% CI; 16 to 95; P < 0.01). During recumbency a non-significant rise was recorded from night- to daytime in albuminuria (22%, -8 to 61, P=0.15), simultaneously with an increase in GFR of 9.0% (3.4 to 14.5, P < 0.005) and mean arterial blood pressure (MABP) of 8.0% (4.3 to 11.7, P < 0.0001). No diurnal variation in fractional clearance of albumin was found. Significant associations between MABP and albuminuria were demonstrated during night- (R2=0.50; P < 0.001) and daytime (R2=0.48; P < 0.005). A linear regression analysis between diurnal variations in MABP and GFR showed that an increase in MABP (of 10%) from night- to daytime was associated with a significant increase in GFR (of 8.0%, 0.2 to 4.1, P < 0.02). CONCLUSIONS: Our study revealed diurnal variations in GFR, albuminuria and MABP in diabetic nephropathy, with lowest values during sleep at night. The observed diurnal variation in albuminuria seems to be explained partly by mechanisms related to orthostasis, and partly by the diurnal variation in GFR and serum albumin concentration. The diurnal variation of blood pressure seems to play a role for the diurnal changes in GFR and albuminuria. PMID- 11786098 TI - Possible role of adenosine in macula densa control of glomerular hemodynamics. AB - BACKGROUND: The macula densa (MD), a plaque of specialized tubular epithelial cells, senses changes in tubular NaCl concentration and sends a signal(s) that controls the resistance of the glomerular afferent arteriole (Af-Art). This mechanism, called tubuloglomerular feedback (TGF), is thought to be important in the homeostasis of body fluids and electrolytes. Our aim was to determine the range of NaCl concentrations in tubular fluid at the MD that would elicit the Af Art response. In addition, we examined the possible involvement of adenosine in transmitting the signal from the MD to the Af-Art. METHODS: Rabbit Af-Arts and attached MD were simultaneously microperfused in vitro, keeping pressure in the Af-Art at 60 mm Hg. RESULTS: Increasing the Na+/Cl- concentration of the MD perfusate from 26/7 to 41/22 mEq/L decreased the luminal diameter of the terminal Af-Art segment by 10 +/- 4% (N=9; P < 0.01). The response was maximal at 55/36 mEq/L (18 +/- 6%), so that further elevation of NaCl concentration had no additional effect (20 +/- 6% at 84/65 mEq/L). When FK838 (10(-6) mol/L), a specific adenosine A1 receptor antagonist, was added to both Af-Art perfusate and bath, Af-Art constriction was completely abolished. The maximum response was 20 +/- 3% before FK838 and 0.6 +/- 1% afterward (N=12). Adding adenosine at 10(-8) mol/L to both bath and perfusate significantly augmented Af-Art constriction induced by increased NaCl at the MD (P < 0.01); however, adding 10-8 to 10-6 mol/L adenosine to the MD perfusate had no effect regardless of the NaCl concentration at the MD. CONCLUSIONS: These results demonstrate that MD control of Af-Art resistance is induced by relatively low NaCl concentrations at the MD, and that activation of the adenosine A1 receptor in the vascular and interstitial space (but not the tubular lumen) may be essential for signal transmission from the MD to the Af-Art. PMID- 11786099 TI - Effects of connexin-mimetic peptides on nitric oxide synthase- and cyclooxygenase independent renal vasodilation. AB - BACKGROUND: Research on the physiological role of endothelium-derived hyperpolarizing factor (EDHF) is hampered by the persistent controversy on its nature and mechanisms of action, as well as by the lack of specific inhibitors that are suitable for in vivo use. Recent in vitro studies support a role for gap junctions in EDHF-mediated signal transmission. The present study examines the contribution of gap junctional communication to the EDHF-mediated responses in the rat renal microcirculation in vivo and addresses the physiological role of EDHF. METHODS: The effects of intrarenal administration of connexin-mimetic peptides on the L-NAME- and indomethacin-resistant renal blood flow (RBF) response to acetylcholine, on basal RBF and on systemic blood pressure were examined. RESULTS: 43Gap 27, a peptide homologous to the second extracellular loop of connexin 43, partially inhibited the L-NAME- and indomethacin-resistant RBF response to acetylcholine, whereas 40Gap 27, homologous to the second extracellular loop of connexin 40, abolished the response. A control peptide, with a replacement of two amino acids in the motif SRPTEK present in the second extracellular loop of connexins 40 and 43, was without effect. None of the peptides affected the response to DETA-NONOate, pinacidil or papaverine. Intrarenal infusion of 43Gap 27 or 40Gap 27 decreased basal RBF and increased mean arterial blood pressure, both in the presence and absence of systemic infusion of L-NAME and indomethacin. CONCLUSIONS: Inhibition of gap junctional communication with connexin-mimetic peptides blocks EDHF-mediated signal transmission in vivo, as suggested by the abolishment of L-NAME- and indomethacin resistant renal vasodilation. The peptides also decrease basal RBF and increase blood pressure, supporting a role for tonic EDHF release in the control of tissue perfusion and vascular resistance. PMID- 11786100 TI - Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. AB - BACKGROUND: Angiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus (DM). METHODS: After two weeks of streptozotocin-induced DM, rats received either no treatment, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for two weeks. At four weeks, renal expression of the p47phox component of NAD(P)H oxidase, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and nitrotyrosine were evaluated by Western blot and immunohistochemistry and related to plasma lipid peroxidation products (LPO), hydrogen peroxide production in the kidney and 24-hour protein excretion. RESULTS: Immunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO, renal hydrogen peroxide production and nitrotyrosine deposition. Expression of nNOS was unaltered. Treatment with either ACEI or ARB prevented all these findings and also prevented significant microalbuminuria. The treatments did not affect the elevated blood sugar, nor did DM or its treatment affect the blood pressure or the creatinine clearance. CONCLUSION: Early proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM. PMID- 11786101 TI - Predictors of proteinuria and renal failure among women with HIV infection. AB - BACKGROUND: Glomerular disease with proteinuria and renal failure are complications of human immunodeficiency virus (HIV) infection. While studies suggest risk factors for both include black race and lower CD4 lymphocyte count, they have not been established in population-based cohorts. This study examines the risk factors for proteinuria and renal failure in a large cohort of HIV infected women not selected for the presence of renal disease. METHODS: This prospective cohort includes 2059 women enrolled in the Women's Interagency HIV study (WIHS). WIHS is a longitudinal study of the clinical course of HIV infection in which subjects are followed biannually with a detailed exam including urine analysis, serum creatinine, CD4 lymphocyte count, and HIV RNA level. Proteinuria was defined as > or =+1 on urine dipstick exam on at least two consecutive urine analyses, and renal failure was defined as a doubling of serum creatinine. Multivariable logistic regression was used to estimate the associations between clinical variables and the presence of proteinuria on initial evaluation in a cross-sectional analysis. Cox proportional hazards regression was used to estimate the associations between clinical variables and time to renal failure among study participants with proteinuria in a prospective longitudinal analysis. RESULTS: Of 2057 HIV-positive women, 32% (N=671) had proteinuria on initial evaluation. Predictors of proteinuria include increasing (log) HIV RNA level [odds ratio (OR)=1.05], black race (OR=2.0), absolute CD4 lymphocyte count < or =200 cells/mm3 (OR=1.41), and the presence of hepatitis C antibody (OR=1.27; all P < 0.0001). Absolute CD4 lymphocyte count < or =200 cells/mm3 [hazard ratio (HR)=3.57, P=0.001], detectable HIV RNA level (HR=2.33, P=0.02), increasing systolic blood pressure (HR=1.02, P=0.002), and decreasing albumin (HR=3.33, P=0.0001) and increasing creatinine (1.67, P=0.0001) were all associated with the development of renal failure. CONCLUSIONS: This analysis establishes the associations between both increasing HIV RNA level and decreasing CD4 lymphocyte count with the presence of proteinuria and occurrence of renal failure. Additionally, it demonstrates an association between proteinuria and a positive hepatitis C antibody. To lessen the presence and progression of renal disease among HIV-infected patients, future research should focus on suppression of the HIV RNA level and improvement in CD4 lymphocyte count. PMID- 11786102 TI - Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy. AB - BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall. PMID- 11786103 TI - Lipoprotein particle abnormalities and the impaired lipolysis in renal insufficiency. AB - BACKGROUND: Increased concentrations of very low- (VLDL) and intermediate-density (IDL) lipoproteins in chronic renal failure (CRF) are thought to result from a defect(s) in degradation of plasma triglyceride (TG)-rich lipoproteins. The purpose of this study was to identify lipoprotein abnormalities associated with the reduced lipolytic rate constant, k1, of combined VLDL and IDL substrate from renal patients and asymptomatic controls. METHODS: The VLDL + IDL were isolated from 18 predialytic patients (CRF-I), 8 patients on hemodialysis (CRF-II) and 10 asymptomatic controls. The lipolytic rate constant (k1) of VLDL + IDL was measured by an assay using bovine milk lipoprotein lipase and determination of TG before and after incubation by gas chromatography (GC). Neutral lipids were measured by GC and apolipoproteins by electroimmunoassays; the apolipoprotein defined TG-rich lipoproteins including Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E were determined by immunoaffinity chromatography. RESULTS: The k1 values of VLDL + IDL were significantly (P < 0.001) lower in CRF-I and CRF-II patients (0.0341 and 0.0352 min-1, respectively) than controls (0.0515 min-1). The levels of apolipoproteins B, C-III and E, and TG-rich Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E particles normalized to 100 mg TG per VLDL + IDL were significantly higher in both groups of CRF patients than in controls. All three TG-rich lipoproteins were characterized by significantly increased percent contents of free (FC) and esterified (CE) cholesterol and a decreased percentage of TG. The k1 values of the combined CRF-I and CRF-II patient groups showed significant negative correlations (P < 0.001) with FC (r=-0.81) and CE (r=-0.63) and a positive correlation with TG (r=0.72). Among lipoprotein particles, only Lp-A-II:B:C:D:E levels showed a significant negative correlation with k1 values (r=-0.47, P < 0.03). CONCLUSIONS: This study shows that the abnormal neutral lipid composition of all three TG-rich lipoprotein particles and increased concentrations of Lp-A II:B:C:D:E particles represent the main factors affecting the in vitro lipolytic rates of VLDL + IDL substrate in both the CRF patients before dialysis and patients on hemodialysis. PMID- 11786104 TI - Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy. AB - BACKGROUND: Treatment of idiopathic membranous glomerulonephritis (MGN) is a controversial issue. Whereas some authors recommend early immunosuppressive treatment of all patients with nephrotic syndrome, others do not support aggressive therapies, based on the spontaneous long-term favorable outcome of most patients. However, 20 to 50% of untreated patients develop progressive renal insufficiency. METHODS: All of the patients with biopsy-proven MGN who developed renal insufficiency at our Hospital during the period of 1975 to 2000 were studied. Selected patients (N=39) were separated into two groups according to the two different therapeutic policies followed at our department: a conservative approach during the first period, 1975 to 1989 (group I, N=20), and a course of immunosuppressive therapy (oral prednisone for six months and concurrent oral chlorambucil, 0.15 mg/kg/day, during the first 14 weeks) during the second period, 1990 to 2000 (group II, N=19). RESULTS: There were no significant differences between both groups at the time of renal biopsy, nor at the onset of renal function decline. All group I patients showed a progressive renal insufficiency; at the end of the follow-up 13 patients (65%) were on chronic dialysis, 2 (10%) showed advanced renal failure, and 5 (25%) had died. In contrast, most of group II patients showed an improvement or stabilization of serum creatinine (SCr; 2.3 +/- 0.9 mg/dL at onset of treatment, 2 +/- 1.5 mg/dL at the end of follow-up) together with decreased proteinuria (11.2 +/- 3.3 vs. 5.2 +/- 6.7 g/24 h). At the end of the follow-up 58% of group II patients had a SCr value < or =1.5 mg/dL and 36% showed a complete or partial remission, whereas no patient in group I showed remission. After four years of follow-up the probability of renal survival without dialysis was 55% in group I and 90% in group II (P < 0.001), and after seven years the renal survival was 20% and 90%, respectively (P < 0.001). Side effects of immunosuppressive treatment were uncommon but severe, as two patients suffered Pneumocystis carinii pneumonia. CONCLUSION: A course of immunosuppressive treatment administered early at the onset of renal function decline induces a favorable effect in most of patients with MGN and deteriorating renal function. Untreated patients progressed without exception toward advanced renal failure. PMID- 11786105 TI - Role of short-term regulatory mechanisms on pressure response to hemodialysis induced hypovolemia. AB - BACKGROUND: A large inter-subject variability exists in the arterial pressure response to hemodialysis-induced blood volume (BV) withdrawal. We investigated the hypothesis that this variability is due to the inter-subject differences in the short-term reflex capacity to compensate for hypovolemia. METHODS: Mean arterial pressure (MAP), heart rate (HR) and the percentage reduction in BV (%R BV) were recorded in 32 subjects during their regular hemodialysis sessions. On the basis of absolute MAP changes between the beginning and the end of the session with respect to %R-BV at the end of the session, three distinct pressure responses were identified: (1) hypotension-prone response; (2) unstable response with delayed hypotension; and (3) hypotension-resistant response. For each kind of response, one patient was selected and a computer model of the cardiovascular system including the main short-term reflex compensatory mechanisms was used to analyze data collected over five consecutive sessions. The %R-BV and HR were used as model inputs, while simulated arterial pressure was fitted to the measured MAP by the tuning model parameters representing the efficiency in the control of venous capacity, microvascular resistance and heart inotropism. RESULTS: The model-based analysis related the hypotension-prone response to a lack of efficacy in capacity and resistance regulation. In the unstable response with delayed hypotension, the control of venous capacity was not effective and resistance control alone kept the pressure stable only for a limited %R-BV reduction (<5%). In the hypotension-resistant response, an efficient compensation of capacitance vessels was evidenced, and the slightly increasing arterial pressure was referred to a prevalence of cardiopulmonary pathway in the compensatory process. CONCLUSIONS: The model ascribes differences in pressure response to differences in the effectiveness of reflex compensatory mechanisms. PMID- 11786106 TI - Quality of life in peritoneal dialysis patients: decline over time and association with clinical outcomes. AB - BACKGROUND: Quality of life (QoL) is increasingly well recognized as an important measure of treatment outcome. The aim of this study was to determine which key factors affect QoL, which aspects of QoL change over time, and if measurements of QoL were associated with clinical outcome in our peritoneal dialysis (PD) population. METHODS: The results of 88 patients (70% of our PD population) enrolled in longitudinal studies of dialysis adequacy, nutrition, and quality of life were reviewed. The sample comprised Indo-Asian [N=35 (diabetic N=18)], and white Europeans [N=53 (diabetic N=18)] heritage. At enrollment (>3 months on PD) demographic data was recorded. At enrollment, and six-month intervals, the dialysis adequacy, nutritional status, QoL (using the KDQOL-SF instrument), hospital admissions, PD infections, and changes in treatment modality were recorded. RESULTS: Male gender, Asian ethnicity, and poor nutritional status as measured by Subjective Global Assessment were the most significant characteristics independently associated with worse overall QoL dimension scores (physical health, mental health, kidney disease issues, patient satisfaction). Comorbidity, months of renal replacement, social deprivation and serum albumin were related to some of the 19 health domains measured. QoL declined steadily during the two-year study period. The most significant changes were for the items general health symptoms/problems, burden of kidney disease, emotional well-being, and patient satisfaction. Increased hospital admissions were associated with a worse QoL. CONCLUSIONS: Quality of life declines in patients on PD over time. Certain aspects of QoL are especially poor in Asian and male patients. This study suggests that further research is necessary to determine the effects of interventions directed at enhancing emotional and social support. PMID- 11786107 TI - Patients with Fabry disease on dialysis in the United States. AB - BACKGROUND: : Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS: : Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS: : During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION: : End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities. PMID- 11786108 TI - Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD. AB - BACKGROUND: Patients on conventional hemodialysis lose residual renal function more rapidly than patients on continuous ambulatory peritoneal dialysis (CAPD). The effect of dialysis using synthetic membranes and ultrapure water is less clear. METHODS: The decline of urea clearance was compared in a cohort of 475 incident end-stage renal failure patients who received treatment with CAPD (N=175) or hemodialysis (HD) utilizing high-flux polysulphone membranes, ultrapure water, and bicarbonate as the buffer (N=300). RESULTS: CAPD patients were significantly younger, fitter (lower comorbidity severity score), less dependent (higher Karnofsky performance score) and less likely to have presented late than HD patients. There was no difference in the mean urea clearance in each group at dialysis initiation, or at any 6-month time point during the ensuing 48 months. This was true even after exclusion of patients who had died in the first year after initiation, those transferred to another dialysis modality, or those who had been transplanted. Only age and chronic interstitial disease predicted retention of urea clearance at one year. The rate of decline of urea clearance was similar in pre- and post-dialysis initiation phases, though there may have been a step-decline of about 2 mL/min at initiation, which requires further investigation. CONCLUSIONS: In hemodialysis using high-flux biocompatible membranes and ultrapure water, residual renal function declines at a rate indistinguishable from that in CAPD. This may have important implications, since preservation of residual renal function has major benefits and is a valid therapeutic goal. PMID- 11786109 TI - Relationship between volume status and blood pressure during chronic hemodialysis. AB - BACKGROUND: The relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial. METHODS: We determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross sectional analysis of a subset of patients (N=468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD. RESULTS: Predialysis systolic and diastolic BP values were 153.1 +/- 24.7 (mean +/- SD) and 81.7 +/- 14.8 mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 +/- 22.7 and 73.9 +/- 13.6 mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 +/- 1.3 kg and plasma volume was contracted by 10.1 +/- 9.5%. Multiple linear regression analyses showed that each kg reduction in body weight during HD was associated with a 2.95 mm Hg (P=0.004) and a 1.65 mm Hg (P=NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50 mm Hg (P=0.026) and a 2.56 mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP. CONCLUSIONS: HD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload. PMID- 11786110 TI - Dialysate calcium profiling during hemodialysis: use and clinical implications. AB - BACKGROUND: Low dialysate calcium (LdCa) concentration is used to prevent or treat hemodialysis (HD)-induced hypercalcemia, but its use has been complicated by intradialytic hypotension in some patients. Our goal was to explore the possibility that dialysis calcium profiling (dCaP) can ameliorate intradialytic hypotension in HD patients who need to have dialysis performed with LdCa. METHODS: In a randomized crossover design, eighteen HD patients underwent one four-hour HD session with LdCa of 1.25 mmol/L (LdCa group) and one four-hour HD session with LdCa of 1.25 mmol/L during the first two hours and high dCa of 1.75 mmol/L during the remaining two hours (dCaP group). After that, they underwent another four-hour HD session with medium dCa of 1.5 mmol/L (MdCa group). Before HD and at four 60-minute intervals during the HD sessions, blood pressure (BP), heart rate (HR) and noninvasive measurements of cardiac index (CI), using bioelectrical impedance, were obtained. Ionized serum calcium (iCa) also was measured before HD and at 120 and 240 minutes into the HD session. In a separate study, eight HD patients were treated for three weeks with 1.25 mmol/L dCa and three weeks with the dCaP technique described above, in random order. A three week treatment with MdCa followed. BP and symptoms were recorded during each HD session. RESULTS: During the LdCa treatment the iCa values remained unchanged, whereas mean arterial pressure (MAP) and CI decreased by 16.5 +/- 8.3% and 14.2 +/- 14.6%, respectively, at the end of HD. During the first half of the dCaP treatment, iCa, MAP and CI decreased by 2.2 +/- 4.1%, 12.6 +/- 12.3%, and 9.6 +/- 13.4%, respectively, whereas during the second half of the same treatment, iCa, MAP and CI values increased by 10.2 +/- 3.3%, 7.8 +/- 7.2% and 10.8 +/- 9.1%, respectively, from the middle HD values. ANOVA showed that the time x treatment effect was significant for iCa, MAP and CI. Total peripheral resistance and HR changes were insignificant and similar among treatments. Hemodynamic effects were comparable between LdCa and MdCa treatments. Intradialytic events were reduced (P < 0.05) only with the dCaP treatment. CONCLUSIONS: The drop in BP observed during the last two hours of HD in both the LdCa and MdCa groups was abolished in the dCaP group. The latter was accomplished via an increase in cardiac output, due to an iCa-induced increase in myocardial contractility. Therefore, dCaP, by individualizing the dCa concentrations used and timing the switching between them, may improve intradialytic BP instability and simultaneously minimize the risk for HD patients to develop hypercalcemia. PMID- 11786111 TI - 1alpha,25-dihydroxyvitamin D3 shows strong and additive immunomodulatory effects with cyclosporine A in rat renal allotransplants. AB - BACKGROUND: Vitamin D3 and its metabolites have long been found to exert immunosuppressive effects both in vivo and in vitro. The present study investigated the effect of 1alpha,25-dihydroxycholecalciferol (1,25DHC) on vascularized renal allografts in rats. METHODS: Three days prior to transplantation, two groups of animals were subjected to 1,25DHC (1 microg/kg/day IP) and a low calcium diet, which was continued until the end of the experiments. Recipient organs were removed and single allografts were transplanted in a high responder strain combination (ACI --> Lewis). Following transplantation, low-dose cyclosporine A (3.2 mg/kg/day CsA) administration was started in two experimental groups of recipients (one group receiving 1,25 DHC additionally) whereas the control allograft recipients received no immunosuppression (control III). Graft survival and renal function was monitored until death or the end of experiments and allograft rejection was assessed histologically using the Banff classification. RESULTS: 1,25DHC significantly prolonged allograft survival in comparison to control III (9.6 +/- 1 vs. 5.7 +/- 0.2 days; P=0.009). In addition, a combination of 1,25DHC and low-dose CsA increased allograft survival compared to CsA administration alone (24 +/- 0.9 vs. 13 +/- 0.3 days; P=0.008). 1,25DHC preserved renal creatinine clearance and decreased proteinuria in comparison to control III, and the combination of 1,25DHC and low-dose CsA again showed an additive effect on preservation of renal function. 1,25DHC and low-dose CsA both decreased interleukin (IL)-2 and IL-12 expression levels in serum and allografts, and a combination treatment produced the strongest attenuation of IL-2 and IL-12 expression. In addition, 1,25DHC increased IL-4 and IL-10 expression levels in allografts, whereas CsA alone did not alter IL-4 and IL-10 expression. In contrast, combination of 1,25DHC and low-dose CsA showed a significant increase in IL-10 expression levels whereas IL-4 expression was not elevated. CONCLUSION: Monotherapy with 1,25DHC significantly prolongs survival of renal allografts and preserves graft function in rats. A combination of 1,25DHC and CsA caused an additive effect on graft survival with differential regulation of pro- and anti inflammatory cytokines, as compared to 1,25DHC administration alone. PMID- 11786112 TI - HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. AB - BACKGROUND.: Patients with end-stage renal disease (ESRD) suffer from markedly higher rates of cardiovascular disease than the general population. Although therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been demonstrated to reduce the mortality from cardiovascular disease in patients without ESRD, only 10% of patients on dialysis are treated with these medications by day 60 of ESRD. We determined whether the use of statins is associated with a reduction in cardiovascular-specific death and total mortality in ESRD patients. METHODS: Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Wave-2 study, a cohort of randomly selected patients who were initiating dialysis in 1996. Information about the use of statins as well as other baseline characteristics was abstracted from the patients' dialysis records by dialysis personnel. Cox proportional hazards models were developed to determine the association between use of statins at baseline and subsequent risk of mortality, with adjustment for known mortality risk factors. RESULTS: Follow-up data were available for 3716 patients through July 1998. At baseline, 362 (9.7%) of patients were using statins. These patients had a mortality rate of 143/1000 person-years, compared with a rate of 202/1000 person-years for patients not using statins. Statin use was independently associated with a reduced risk of total mortality [relative risk (RR)=0.68, 95% confidence interval (CI)=0.54, 0.87] as well as cardiovascular-specific mortality (RR=0.64, 95% CI=0.45, 0.91). In contrast, the use of fibrates was not associated with reduced mortality (RR=1.29). CONCLUSIONS: Statin use was associated with a reduction in cardiovascular-specific death and total mortality in patients on dialysis. PMID- 11786113 TI - Vascular access use in Europe and the United States: results from the DOPPS. AB - BACKGROUND: A direct broad-based comparison of vascular access use and survival in Europe (EUR) and the United States (US) has not been performed previously. Case series reports suggest that vascular access practices differ substantially in the US and EUR. We report on a representative study (DOPPS) which has used the same data collection protocol for> 6400 hemodialysis (HD) patients to compare vascular access use at 145 US dialysis units and 101 units in five EUR countries (France, Germany, Italy, Spain, and the United Kingdom). METHODS: Logistic analysis evaluated factors associated with native arteriovenous fistula (AVF) versus graft use or permanent access versus catheter use for prevalent and incident HD patients. Times to failure for AVF and graft were analyzed using Cox proportional hazards regression. RESULTS: AVF was used by 80% of EUR and 24% of US prevalent patients, and was significantly associated with younger age, male gender, lower body mass index, non-diabetic status, lack of peripheral vascular disease, and no angina. After adjusting for these factors, AVF versus graft use was still much higher in EUR than US (AOR=21, P < 0.0001). AVF use within facilities varied from 0 to 87% (median 21%) in the US, and 39 to 100% (median 83%) in EUR. For patients who were new to HD, access use was: 66% AVF in EUR versus 15% in US (AOR=39, P < 0.0001), 31% catheters in EUR vs. 60% in US, and 2% grafts in EUR vs. 24% in US. In addition, 25% of EUR and 46% of US incident patients did not have a permanent access placed prior to starting HD. In EUR, 84% of new HD patients had seen a nephrologist for> 30 days prior to ESRD compared with 74% in the US (P < 0.0001); pre-ESRD care was associated with increased odds of AVF versus graft use (AOR=1.9, P=0.01). New HD patients had a 1.8-fold greater odds (P=0.002) of starting HD with a permanent access if a facility's typical time from referral to access placement was < or =2 weeks. AVF use when compared to grafts was substantially lower (AOR=0.61, P=0.04) when surgery trainees assisted or performed access placements. When used as a patient's first access, AVF survival was superior to grafts regarding time to first failure (RR=0.53, P=0.0002), and AVF survival was longer in EUR compared with the US (RR=0.49, P=0.0005). AVF and grafts each displayed better survival if used when initiating HD compared with being used after patients began dialysis with a catheter. CONCLUSION: Large differences in vascular access use exist between EUR and the US, even after adjustment for patient characteristics. The results strongly suggest that a facility's preferences and approaches to vascular access practice are major determinants of vascular access use. PMID- 11786114 TI - Urea volume of distribution exceeds total body water in patients with acute renal failure. AB - BACKGROUND: An accurate estimate of volume of distribution of urea (Vurea) is critically important to guide the prescription of therapy and the quantification of delivered dialysis dose in patients with chronic and acute renal failure (ARF). While Vurea has been shown to be substantially the same as total body water (TBW) in other patient populations, this relationship has not been adequately studied in detail in ARF patients. METHODS: To evaluate this question, we undertook a systematic study of these parameters in a cohort of 28 patients with ARF to analyze methods of estimating Vurea and TBW using blood-based kinetic data, anthropometric data and bioelectrical impedance analysis (BIA). RESULTS: The results show that Vurea estimated by double-pool Kt/V (67.9 +/- 19.2 L) and by equilibrated Kt/V (61.2 +/- 13.6 L) were statistically significantly higher than Vurea determined by single-pool Kt/V (55.3 +/- 12.9 L; difference of 16% and 11%, respectively). Determination of TBW by anthropometric measurements (Watson, 42.5 +/- 7.0 L; Hume-Weyer, 43.6 +/- 7.1 L; Chertow, 46.8 +/- 8.1 L) yielded significantly lower measures compared to TBW determined by physiological formulae and by BIA (51.1 +/- 11.6 L and 51.1 +/- 13.3 L, respectively). Most importantly, all measures of Vurea by blood-based kinetics exceeded TBW measurements by any method (7% to 50% difference). CONCLUSION: Our results suggest that in terms of useful guidelines to prescribe a specific dose of dialysis in patients with acute renal failure, estimates of TBW cannot be used as a surrogate for Vurea in determining dialysis adequacy. PMID- 11786115 TI - Low TGF-beta1 serum levels are a risk factor for atherosclerosis disease in ESRD patients. AB - BACKGROUND: It is thought that transforming growth factor-beta1 (TGF-beta1) might be a key inhibitor of atherogenesis in non-uremic patients. We evaluated the intra- and post-dialytic serum levels of TGF-beta1 in uremic patients to assess if TGF-beta1 is an independent risk factor for cardiovascular diseases, and if any correlation exists between TGF-beta1 and any yet known atherosclerotic risk factors. METHODS: We studied 155 patients who were on regular hemodialysis, with or without clinically significant atherosclerotic vascular disease. Forty-one apparently healthy people were enrolled as a control group. TGF-beta1 was evaluated during the midweek dialysis session, at times 0, 30, and 120 minues, at the end of the session, and 3 hours after the session's end. All hitherto known atherosclerotic risk factors also were evaluated. The investigation was performed over a 24-month follow-up. RESULTS: TGF-beta1 values (mean +/- SD) in dialysis patients were 26.64 +/- 7.0 ng/mL (N=155) compared with 42.31 +/- 6.0 ng/mL in the control group (N=41, P < 0.0001). A weak inverse correlation emerged between TGF-beta1 and age (r=-0.28), TGF-beta1 and lipoprotein(a) [Lp(a); r=-0.35], TGF beta1 and C-reactive protein (CRP; r=-0.27), and TGF-beta1 and plasminogen activator inhibitor-1 (PAI-1; r=-0.41). TGF-beta1 also correlated with albumin (r=0.31). In the coronary heart disease (CHD) group (N=32) the TGF-beta1 was 26.2 +/- 4.9 ng/mL; in the cerebrovascular disease (CVD) group (N=8) it was 26.7 +/- 3.7 ng/mL and in the peripheral vascular disease (PVD) group (N=9) it was 25.4 +/ 1.7 ng/mL. In dialysis patients with no cardiovascular disease (N=80) TGF-beta1 was 35.1 +/- 6.8 ng/mL (P < 0.0001 vs. CHD, CVD and PVD patients). TGF-beta1 was significantly lower among those patients with triple coronary vessel disease than with the other CHD patients. The Cox analysis demonstrated that a 1 ng/mL reduction in TGF-beta1 concentration was associated with a 9% increase in the relative risk of a cardiovascular event. CONCLUSIONS: TGF-beta1 was significantly reduced in hemodialysis patients, in particular in those with severe cardiovascular disease. Baseline TGF-beta1, diabetes mellitus and serum albumin levels proved to be the only independent contributors to atherosclerotic risk in dialysis patients. PMID- 11786116 TI - Quantifying porphobilinogen deaminase mRNA in microdissected nephron segments by a modified RT-PCR. AB - BACKGROUND: Quantifying mRNA levels by reverse transcription-polymerase chain reaction (RT-PCR), although widely exercised, is still difficult. METHODS: A modified quantitative RT-PCR in which genomic DNA was used as standard was developed. The quantity of mRNA was expressed as the ratio of the PCR product from cDNA and that from genomic DNA (CG ratio). Nephron distribution of porphobilinogen deaminase (PBGD) mRNA was examined in microdissected nephron segments using the method. The enzyme activity and mRNA quantity of PBGD also were measured in tissue homogenates. RESULTS: Tubular segments expressed substantially more PBGD mRNA than glomeruli (expressed as CG ratios, 1.04 +/- 0.10 in glomeruli, 4.53 +/- 0.32 in PCT, 5.71 +/- 0.25 in PST, 5.13 +/- 0.52 in mTAL, 5.29 +/- 0.20 in cTAL, 4.05 +/- 0.35 in DCT, 2.88 +/- 0.25 in CCD, and 4.90 +/- 0.24 in OMCD). PBGD mRNA level in liver homogenate (3.17 +/- 0.36) was much higher than glomeruli but lower than most of the tubular segments. The enzyme activity in tissue homogenates correlated well with mRNA levels. CONCLUSION: The method reported here is simple and reliable, and especially suitable for quantitating specific mRNA amounts in minute tissue samples such as microdissected nephron segments. PMID- 11786117 TI - Selection of peptide ligands binding to the basolateral cell surface of proximal convoluted tubules. AB - BACKGROUND: Recently, we have reported a novel approach of screening phage display peptide libraries on microdissected intact renal tubular segments and identified an RGD-containing peptide ligand that specifically binds to the basolateral membrane of cortical collecting ducts (CCD). However, screening phage libraries on proximal convoluted tubules (PCT) did not yield a tubule segment specific ligand. Here, we describe the successful modification of our previously developed phage-display approach and the identification of two distinct ligands that bind specifically to receptors expressed at the basolateral membrane of PCT. METHODS: Ex vivo screening of phage-display peptide libraries for specific ligands was adapted for PCT. The previously developed method was significantly extended by applying it to a distinct tubular segment, varying the number of rounds of biopanning and incubating phage libraries with absorber cells prior to biopanning. Binding specificity and cellular localization of selected peptide displaying phage or the corresponding synthetic peptide were analyzed using various epithelial cell lines as well as competition assays and confocal immunofluorescence microscopy. RESULTS: Screening phage-display peptide libraries, depleted of ligands binding to ubiquitously expressed receptors by preincubation with HEK-293 cells, led to the identification of two PCT-specific ligands. Phage expressing peptides with the consensus sequence GV(K/R)GX3(T/S) or RDXR mediated 15-fold and 13-fold higher binding to PCT than control phage, and binding to PCT was 13-fold and 21-fold higher than binding to CCD, respectively. Neither phage mediated significant binding to various epithelial cell lines, and binding of both ligands was abolished by the addition of the corresponding synthetic peptide. Immunofluorescence experiments revealed a submembrane localization of both ligands upon incubation with PCT. CONCLUSIONS: Exploiting the versatility of phage-display and biopanning allowed the identification of two distinct peptide ligands that bind specifically to the basolateral membrane of PCT. Tubule segment-specific ligands, such as the described PCT ligands, may be useful for the analysis of cell-extracellular matrix interactions and may contribute to the development of new therapeutic strategies for renal diseases. PMID- 11786118 TI - Membranous nephropathy: quo vadis? PMID- 11786119 TI - BMP-7 and the proximal tubule. PMID- 11786120 TI - Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia. PMID- 11786121 TI - Reduced content of alpha subunit of Gq protein content in monocytes of Bartter and Gitelman syndromes: relationship with vascular hyporeactivity. PMID- 11786122 TI - Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. PMID- 11786124 TI - Ischemic heart disease after renal transplantation. PMID- 11786125 TI - Current research in management of hematological diseases with poor prognosis. PMID- 11786126 TI - A comparison of spur valve and percutaneous enterostomy in Roux-Y portoenterostomy for biliary atresia. AB - OBJECTIVE: To compare the advantages and disadvantages of two procedures: Roux-Y with enterostomy and Roux-Y with spur valve in the treatment of biliary atresia. METHODS: Twenty-four patients with biliary atresia underwent hepatic portoenterostomy with percutaneous jejunal enterostomy (Group A) and 24 patients underwent Roux-Y with antireflux spur valve (Group B). Clinical data were reviewed retrospectively. RESULTS: Ten patients remained alive in the Group A. Among them, 9 survived without jaundice, the oldest one being 9-years old. One of the 9 patients had portal hypertension. The remaining one who survived with jaundice and portal hypertension was 8-years old at follow up. Ten patients in the Group B remained alive. Of them, 8 survived without jaundice and 2 with jaundice. CONCLUSIONS: Two surgical procedures had similar effects in preventing reflux cholangitis, while spur valve has the benefit of quitting cutaneous enterostomy. PMID- 11786127 TI - [Delay in the performance of diagnostic tests and unnecessary hospital stays in lung cancer]. AB - OBJECTIVES: To report among hospitalised patients the proportion of admissions and inappropriate stays, causes for inappropriateness and length in diagnosis delay. To analyse the relationship between patient's characteristics, length of stay and inappropriate use of hospitalization; to evaluate the association between requesting diagnostic tests, stay prolongation and unnecessary use of hospitalization. METHODS: Prospective cohort of 118 admitted patients because of bronchopulmonary cancer at a university teaching hospital. Length of stay, inappropriate stays and delays in diagnostic tests were analysed. RESULTS: The mean hospital stay was 16.3 days, with 74.2% of unnecessary stays and relevant intrahospital diagnostic delays, with over five days for obtaining a chest X-ray, almost seven for a computerized tomography, and eight to have pathology results available. The proportion of inappropriate stays was associated with the number and type of requested tests. CONCLUSIONS: The results of this study suggest a number of possibilities to improve care quality to patients with suspect of lung cancer, both avoiding unnecessary admissions and shortening diagnostic delays. Also, care costs are reduced and hospital beds are reserved for those patients whose clinical status warrant hospital admission. PMID- 11786128 TI - [Clinical characteristics of patients with essential hypertension regarding salt intake]. AB - A number of epidemiologic and experimental studies have revealed the close relationship between salt intake and blood pressure. The objective of this study was to know the salt intake among 293 not previously treated hypertensive patients and to identify their clinical characteristics that would allow us to define the profile of patients with high sodium intake. Hypertensive patients who first attended a specialized high blood pressure (HBP) clinic not previously treated with drugs, at least for the last month were selected. Sodium 24 h urinary excretion was determined on two occasions, as sodium intake index. Thirteen percent of patients had a salt intake lower than 100 mEq/24 h and 35% of patients higher than 200 mEq/24 h. Sodium intake was higher among men, younger patients, those with a higher Quetelet index, smokers, higher socioeconomic status, and less years with IBP. No differences were observed between salt intake among hypertensive patients with associated diabetes or hyperlipidemia. The Quetelet index, sex, age and smoking were identified as independent variables for salt intake by the multiple linear regression analysis. No correlation was found between salt intake and blood pressure. In conclusion, a high sodium intake was observed in our setting among hypertensive patients who had previously been advised to moderate salt intake. The highest salt intake was observed among men, youths, obese and smokers. PMID- 11786129 TI - [Pyogenic liver abscesses in cancer patients]. AB - OBJECTIVE: To analyse the clinical behaviour of pyogenic liver abscesses among cancer patients, and to determine whether there is any difference between clinical behaviour among patients without malignancies. PATIENTS AND METHODS: Retrospective, multicentric study with 133 patients with pyogenic liver abscesses diagnosed during 13 years. Patients were divided into two groups: 29 patients with malignant tumors identified during the five years prior to abscess development (group 1) and 104 patients without malignant tumors (group 2). Clinical, biological and bacteriological findings, morphology and lesional topography, treatment and particularly, clinical course were analysed. RESULTS: Abscesses with portal pathogenesis were more common in group 1 (24% versus 10%; p = 0.03). Clinical and biological data were similar in both group but jaundice (31% versus 18%; p = 0.09), liver enlargement (38% versus 21%; p = 0.06) and pleural effusion (48% versus 28%; p = 0.03), which were more common in group 1. In the same group, the mean AST level was also higher (112 149 versus 60 88; p = 0.07 ). Morphology and lesional topography, as well as bacteriology in both groups did not differ significantly. In group 1, surgical drainage was performed less frequently (21% versus 38%; p = 0.09) and mortality rate was higher (24% versus 11%; p = 0.08). Nevertheless, no significant differences were observed between hospital stay and morbidity. Among patients treated with antibiotics only, the mortality rate was higher in group 1 (50% versus 10%; p = 0.06). CONCLUSIONS: In pyogenic liver abscess in patients with malignant tumor disease a predominance of portal pathogenesis was observed. The presence of cancer among patients with pyogenic liver abscesses did not imply a significantly different clinical presentation; however, the clinical course was worse than that observed in cases without cancer. PMID- 11786130 TI - [Rendu-Osler-Weber disease. Descriptive study of 17 cases]. AB - OBJECTIVE: To study the prevalence and presentation forms of hereditary hemorrhagic telangiectasia (HHT) among the population in our hospital area. MATERIALS AND METHODS: Descriptive, retrospective study of patients with the diagnosis of HHT from to 1999 at La Fe Hospital, Valencia. Family history, repeated epistaxis, mucocutaneous telangiectasis and visceral lesions, as well as administered treatments, and clinical course were evaluated. RESULTS: Seventeen patients were diagnosed during such time period, with ages ranging from 23 to 80 years. Eight patients had family histories. The most common symptoms included epistaxis and iron-deficiency anemia, followed by muco-cutaneous telangiectasis. Six patients had neurological, five pulmonary, five gastrointestinal, and three hepatic manifestations, usually secondary to vascular malformations at those levels. CONCLUSIONS: The prevalence of the disease maybe higher than previously reported. This disease should be considered in patients with repeated epistaxis and/or iron-deficiency anemia. The presence of telangiectasis that can suggest the diagnosis should be investigated. An early diagnosis of HHT can be useful for the early control of associated visceral malformations. Treatment of HHT should be tailored according to the clinical manifestations of the patient. PMID- 11786131 TI - [Diagnosis and management of post-radiation dryness of mucosas]. PMID- 11786132 TI - [Diagnosis of aortic aneurysm]. PMID- 11786133 TI - [Diagnostic evaluation of fever among patients with systemic autoinmune disease. Infection versus inflammatory activity]. PMID- 11786134 TI - [Serological investigation in septic arthritis. Application to the clinical practice]. PMID- 11786135 TI - [Cardiac changes in the chronic HIV-1 infection]. PMID- 11786136 TI - [Treatment and prognosis of the severe exacerbation in the chronic obstructive pulmonary disease]. PMID- 11786137 TI - [Back pain in a 35-years old male]. PMID- 11786138 TI - [Aorto-caval fistula in ruptured abdominal aorta aneurysm]. PMID- 11786139 TI - [Ecchymosis and dyspnea in a 66-year old male]. PMID- 11786140 TI - [Subungueal amelanotic melanoma]. PMID- 11786141 TI - [Transitory cryoglobulinemia and leptospirosis]. PMID- 11786142 TI - [First grade auriculo-ventricular blocking and syncope due to the use of amphetamines]. PMID- 11786143 TI - [Mediastinal metastases as early manifestation of prostatic carcinoma]. PMID- 11786144 TI - [Unusual localization of brucellosis related arthritis of the shoulder]. PMID- 11786145 TI - Influence of leptin on neurotransmitter overflow from the rat brain in vitro. AB - The 16-kDa polypeptide hormone, leptin along with the neurotransmitters noradrenaline and serotonin (5-HT) have important physiological roles in the regulation of a number of neuroendocrine actions particularly feeding. Leptin receptor mRNA and immunoreactivity has been reported in various brain regions, while recent studies suggest that leptin is released from the human brain. This study investigated the interactions between leptinergic and neurotransmitter systems of the rat brain in vitro. Techniques were established to simultaneously monitor the release of endogenous noradrenaline and its metabolite 3,4 dihydroxyphenylglycol (DHPG), and 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) from the rat brain. The neuromodulatory action of leptin (0.2 and 3 nM) on the overflow of noradrenaline and DHPG from the medulla and hypothalamus was examined. The effect of leptin on 5-HT and 5-HIAA overflow from the hypothalamus was also investigated. Administration of 0.2 and 3 nM leptin significantly increased medullary noradrenaline overflow to 172% and 174% of basal levels, respectively. Leptin had no significant effect on hypothalamic noradrenaline overflow, while leptin perfusion induced a significant increase in 5-HIAA overflow from the hypothalamus. This study lends support to the notion of a complex interaction of the leptinergic and brain neurotransmitters involved in the control of feeding and energy metabolism. PMID- 11786146 TI - Influence of diet composition on food intake and neuropeptide Y (NPY) gene expression in goldfish brain. AB - In this study, goldfish demonstrate preference for high carbohydrate and high fat diets, with no preference shown for high protein diets. Fish fed high (45% and 55%) carbohydrate (CHO) diets for 1 and 4 weeks exhibited decreased NPY gene expression in telencephalon-preoptic area (TEL-POA) and optic tectum-thalamus (OT THAL) compared to fish fed low CHO (35% and 40%) diets. In hypothalamus (HYP), NPY gene expression was significantly increased after 1 week in fish fed both low and high CHO diets compared to control diet (40% CHO); after 4 weeks, the pattern in HYP was reversed. Fish fed a high fat (9%) diet had low NPY gene expression in TEL-POA after 1 and 4 weeks; however, HYP NPY expression was increased in fish fed a low (3%) fat diet after 1 week, and 2% and 3% fat diets after 4 weeks. In OT-THAL, NPY gene expression was decreased in fish fed a 2% fat diet for 1 week, and increased after 4 weeks. Feeding diets with different protein contents for 1 or 4 weeks did not influence NPY gene expression in goldfish brain. The results demonstrate, for the first time in a lower vertebrate, that NPY gene expression in goldfish brain is influenced by macronutrient intake. PMID- 11786147 TI - Lack of a distinctive behavioural effect of chromogranin-derived peptides in rodents. AB - Chromogranins are neuropeptide precursors stored in large dense core vesicles in which they are processed to smaller peptides. Although these peptides are widespread in the CNS, it is still unknown if they are behaviourally active. For example, even though secretoneurin, a 33-amino acid peptide derived from secretogranin II, was shown to induce release of dopamine from rat striatal neurons, work on the functional significance of this result is still missing. In order to investigate the behavioural effects of chromogranin-derived peptides, we studied the total locomotor activity and rearing behaviour of male albino Sprague Dawley rats in the open field experimental paradigm. Measurements were performed every 5 min during half an hour before and 2 h after an intracerebroventricular injection of GE-19, GAIPIRRH, secretoneurin or vehicle. None of the tested chromogranin-derived peptides (at a concentration of 20 microM) affected locomotion and rearing behaviour. However, the administration of secretoneurin and GAIPIRRH increased the thigmotaxis, suggesting a possible anxiolytic action. In male Swiss albino mice, which were tested in the black-and-white box paradigm, only GE-19 produced sedation at a dose of 0.72 nmol in 41% of the mice. Overall, there is only little evidence that any of the examined chromogranin-derived peptides produces a behaviourally significant effect, even when given intracerebroventricularly. PMID- 11786148 TI - Bovine pancreatic secretion in the first week of life: potential involvement of intestinal CCK receptors. AB - The aim of this study was to evaluate pancreatic juice secretion of calves in the first postnatal days, and determine a potential involvement of cholecystokinin (CCK) and intestinal CCK receptor in its regulation. Nine neonatal Friesian calves (five controls and four treated intraduodenally with FK480, a CCK-A receptor antagonist) were surgically fitted with a pancreatic duct catheter and a duodenal cannula before the first colostrum feeding. Collections of pancreatic juice and duodenal luminal pressure recordings were started early after recovery from anaesthesia and continued for 6 days. From day 2 or 3 of life, periodic fluctuations in pancreatic secretions were observed in concert with duodenal myoelectric motor complex (MMC) and variations in plasma pancreatic polypeptide (PP) concentrations. Intraduodenal administration of FK480 reduced pancreatic juice secretion while intravenous infusion of CCK had no effect. Immunocytochemistry indicated an association of mucosal CCK-A and -B receptors with neural components of the small intestine. In conclusion, periodic activity of the exocrine pancreas exists in neonatal calves soon after birth and local neural intestinal CCK-A receptors could be partly responsible for the modulation of neonatal calf pancreatic secretion. PMID- 11786149 TI - Role of neuropeptide Y Y(2) receptors in modulation of cardiac parasympathetic neurotransmission. AB - The aim of the study was to clarify the role of the Y(2) receptor in regulation of vagal control of the heart, using Y(2)((-/-)) receptor-knockout mice. Adult Y(2)((+/+),(-/-)) mice (50% C57BL/6-50% 129/SvJ background) were anaesthetised and artificially ventilated. Arterial blood pressure and pulse interval was recorded and both vagus nerves were cut. The cardiac end of the right vagus nerve was stimulated supra-maximally every 30 s (7 V, 2-2.5 Hz, 5 s). Neuropeptide Y (NPY) and a Y(2) receptor agonist, N-acetyl [Leu(28, 31)]NPY 24-36, were injected intravenously in both groups of mice. N-acetyl [Leu(28, 31)] NPY 24-36 was also administered to control mice in the presence of a Y(2) receptor antagonist, BIIE0246. Stimulation of the vagus nerve increased pulse interval (PI) by approximately 100 ms. NPY and N-acetyl [Leu(28, 31)] NPY 24-36 attenuated the increase in PI evoked by vagal stimulation in control mice only. The attenuation was reduced in the presence of BIIE0246. The results presented here show in Y(2)((-/-)) receptor-knockout mice that NPY and N-acetyl [Leu(28, 31)] NPY 24-36 have no effect on PI evoked by vagal stimulation. These findings demonstrate that NPY attenuates parasympathetic activity to the heart via the Y(2) receptor. PMID- 11786150 TI - MADIT II, the Multi-center Autonomic Defibrillator Implantation Trial II stopped early for mortality reduction, has ICD therapy earned its evidence-based credentials? AB - In a press conference on Nov. 20, 2001 it was announced that the Multi-center Autonomic Defibrillator Implantation Trial II (MADIT II) was stopped early because of a 30% reduction in mortality in patients randomised to receive an implantable defibrillator device. The 4 year multi-centre trial of 1200 patients was terminated early after an independent board observed that the post-MI patients with impaired left ventricular function receiving the implantable defibrillator had improved survival rates compared to those receiving conventional treatment. The MADIT II trial's aim was to test whether an AICD will reduce mortality in high-risk patients with coronary artery disease and left ventricular dysfunction with no arrhythmia entry criteria. The intention was to recruit 1200 patients aged 21-85 years with left ventricular ejection fraction (EF) 16% (n=108), respectively, calculated from a preoperative RAO ventriculogram. There was no difference in EF between the two groups (26.5+/ 5.5 vs. 27.8+/-5.3%, respectively). Eight (9.9%) versus three (2.8%) patients died perioperatively in the low versus the high WMS group, respectively. The relative risk for perioperative death in the low WMS group was 3.6 (P<0.04). Kaplan-Meier estimates of cumulative survival did not reveal any statistical difference between the two groups over 4 years (P=0.11). Subgroup analysis revealed that patients with a WMS of 16% were not significantly different, although subgroup analysis revealed that patients with a WMS 100 ng/ml) were collected from 22 patients with severe sepsis and were pooled for further purification (12.7 microg total concentration of PCT). Pooled PCT was purified on a CT 21-immunoaffinity column, further purified by reversed phase HPLC, and the resulting pure PCT was digested with endoproteinase Asp-N. N-terminal Edman sequencing showed that the first two amino acids (Ala-Pro) of the proposed pro-peptide were missing. Further analyses by MALDI-TOF mass spectroscopy resulted in a distinct mass signal of 12640 Da +/- 0.1%, which is in concordance with the theoretical molecular weight of the N-terminal truncated form (12628 Da). As opposed to previous suggestions, we could not detect any chemical modifications of PCT. In summary, we could demonstrate that PCT in the serum of septic patients is a peptide of only 114 amino acids, instead of the predicted 116 amino acids, lacking the N-terminal dipeptide Ala-Pro. This information on the primary structure of PCT might help in further studies on the physiological role of PCT during sepsis. PMID- 11786197 TI - Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. AB - Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states. PMID- 11786198 TI - Role of endogenous cyclo(His-Pro) in voluntary alcohol consumption by alcohol preferring C57BL mice. AB - Cyclo (His-Pro) or CHP is a cyclic dipeptide endogenous to the brain of a variety of animal species including man. Administration of exogenous peptide to rodents has been shown to exhibit a variety of biological activities some of which appear to be mediated via a dopaminergic mechanism. Since a hypodopaminergic state has been associated with excessive drinking in animal models as well as man, we have explored the potential role of CHP in alcohol-preferring C57BL mice. The results of this study show that the level of CHP, a peptide that mimics dopamine in many of its pharmacologic actions, is lower in brains of alcohol-preferring C57BL mice compared to alcohol non-preferring DBA2 mice. Furthermore, administration of exogenous CHP to C57BL mice caused a pronounced decrease in their voluntary alcohol consumption. In conclusion, endogenous CHP may play a role in risk for developing excessive alcohol use by modulating central dopaminergic tone. PMID- 11786199 TI - Effects of peripheral and central administration of GHRH on feeding in aging LOU rats. AB - In aging LOU rats, a decreased protein intake is restored by GH administration. To study the contribution of GHRH to macronutrient selection, hGHRH NH(2) was administered sc. (1 mg/kg B.W./day/14 days) or icv. (4 and 40 pmol/rat) to 11-, 19-, 24- and 28-month-old rats. Sc. administration induced a decreased food and lipid intakes from 24 months of age and a transient stimulation of protein intake in 19-month-old and older low protein eaters (<10% protein/total intake). Icv. administration induced decreased food and lipid intakes in all age groups. These results suggest that GHRH may regulate feeding through pituitary and/or hypothalamic GHRH receptor mechanisms. PMID- 11786200 TI - Validity of multiple-time regression analysis in measurement of tritiated and iodinated leptin crossing the blood-brain barrier: meaningful controls. AB - Multiple-time regression analysis has been used to study the influx of radiolabeled peptides and polypeptides across the blood-brain barrier (BBB). This study used both tritiated and iodinated leptin to clarify several issues associated with these measurements. Recombinant murine leptin was radiolabeled with 3H by derivatization or with 125I by the iodobead method and each studied separately in mice. Intact 3H-leptin had a higher apparent influx rate from blood to brain than did intact 125I-leptin, correlating with its higher proportion of reversible association with the capillary lumen that would misleadingly appear to reflect entry. Yet the majority of 3H-leptin and 125I-leptin reached brain parenchyma. There was no significant difference in the influx rate between cerebral cortex and the subcortical regions, thus ruling out a predominant contribution of simple diffusion through the circumventricular organs or choroid plexuses outside the BBB. The influx of radiolabeled leptin, especially 125I leptin, was decreased by excess unlabeled leptin, supporting the presence of a saturable transport system for leptin at the BBB. To identify the specificity of the transport system and determine whether it is shared by 3H-leptin and 125I leptin, these radioactively labeled leptins were heat-denatured. Denaturation had no effect on the fast influx of 3H-leptin, but abolished the entry of 125I-leptin into brain; excess denatured leptin failed to inhibit the influx of either 3H leptin or 125I-leptin. This indicates that the conformation of 125I-leptin is similar to that of native unlabeled leptin, so that iodination would be the better choice for investigating the interaction of leptin with the BBB. However, 3H-leptin can use the same transport system, as shown by inhibition of its influx by unlabeled leptin, whereas the derivatization procedure altered its biophysical properties such that its non-saturated influx was greatly enhanced. Finally, the rapid influx of radioactively labeled leptin contrasted greatly with that of the reference compounds 99mTc-albumin and 3H-inulin which had no significant penetration of the BBB. Thus, with additional considerations such as stability and interactions with the vasculature, multiple-time regression analysis is sensitive and selective for study of the penetration of peptides across the BBB. PMID- 11786201 TI - Interactions among challenges of hydromineral balance, angiotensin-converting enzyme, and cystine aminopeptidase. AB - Enzymatic cleavage of some peptides could be included among the mechanisms of water-electrolyte homeostasis. To test this hypothesis, the angiotensin converting activity (ACE) of plasma and the L-cystine-di-beta-naphthylamidase activity (CAP) of plasma and of soluble and particulate fractions from different areas of the central nervous system (CNS) were investigated in rats submitted to treatments eliciting hydromineral imbalance. CAP in the CNS was unchanged by hydromineral challenges. The correlations observed between plasma osmolality and CAP, and plasma CAP and ACE suggested a contribution of these activities to the restoration of basal water-electrolyte and blood pressure conditions through the hydrolysis of vasopressin, oxytocin, angiotensin I and bradykinin. PMID- 11786202 TI - Role of Asp297 of the AT2 receptor in high-affinity binding to different peptide ligands. AB - To determine how ligand-receptor interaction is affected by the charges of the amino acids at position 2 of the ligands and position 297 of the AT2 receptor, we generated the Asp297Lys mutant of AT2 and a ligand SarAsp(2)Ile. Asp297Lys mutant lost affinity to Ang II and SarIle however retained partial affinity to 125I CGP42112A. The SarAsp(2)Ile had high affinity to Asp297Lys (IC(50)3.5nM) and partial affinity to the AT2 (IC(50)15nM). Therefore, not only the charge, but also the length of the side arms of the amino acids at position 2 of the ligand and position 297 of the receptor affect their interaction. PMID- 11786203 TI - Pituitary adenylate cyclase-activating peptide inhibits neutrophil chemotaxis. AB - Pituitary adenylate cyclase-activating peptide 38 (PACAP 38) is a neuropeptide that displays several biological effects of interest in the context of airway diseases such as asthma and chronic obstructive pulmonary disease. These effects include inhibition of airway and vascular smooth muscle tone as well as modulation of inflammatory cell activity. However, little is known about the effect of PACAP on granulocytes. The present study was designed to investigate if PACAP and the closely related peptide vasoactive intestinal peptide (VIP) could affect neutrophil migration. A standard 48 well chemotaxis chamber was used to assess the effects of PACAP on N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced neutrophil chemotaxis and spontaneous random migration. PACAP 38 and VIP inhibited fMLP-induced human neutrophil chemotaxis. Furthermore, both peptides also exhibited a dose-related trend toward inhibiting the spontaneous, unstimulated migration of neutrophils. Since enhanced cell migration in cell chamber systems is reported to correlate with increased invasive properties in vivo, the presented inhibitory effects of PACAP 38 on neutrophil chemotaxis, supports the idea of an anti-inflammatory role for PACAP. This together with the well documented bronchodilatory capacity of PACAP might indicate a role for PACAP agonists in future treatment of asthma and other inflammatory airway diseases. PMID- 11786204 TI - Characterization of functional VIP/PACAP receptors in the human erythroleukemic HEL cell line. AB - The presence of VIP/PACAP receptors was investigated on the human erythroleukemic cell line HEL. Specific binding of [125I]-PACAP or [125I]-VIP on HEL cells or membranes was very low and did not allow to perform competition curves. At 37 degrees C PACAP transiently increased cAMP levels in the presence of the non specific phosphodiesterase inhibitor IBMX, suggesting rapid desensitization. Kinetic studies revealed that optimal conditions to measure the EC(50) of PACAP(1 27) were 10 min at 20 degrees C. Under those conditions, PACAP-related peptides increased cAMP levels with EC(50) in agreement with the pharmacological profile of the VPAC(1) receptor subtype: PACAP = VIP > [K(15), R(16,) L(27)]VIP(1 7)/GRF(8-27) = [R(16)]ChSn (two VPAC(1) agonists) >> helodermin = secretin. RO 25 1553, a selective activator of VPAC(2) receptor was inactive at 1 microM. Dose response curves of VPAC(1) agonist molecules (PACAP, VIP, [K(15), R(16), L(27)]VIP(1-7)/GRF(8-27), [R(16)]ChSn) were shifted to the right by the VPAC(1) receptor antagonist [AcHis(1), D-Phe(2), Lys(15), Leu(17)]VIP(3-7)/GRF(8-27), with a K(i) of 3 +/- 1 nM (n = 3). The presence of VPAC(1) receptor mRNA was confirmed by RT-PCR. Preincubation with PACAP or PMA showed that VPAC(1) receptors underwent homologous and heterologous desensitization. This study provides the first evidence for the expression of functional VPAC(1) receptors undergoing rapid desensitization in HEL cells. PMID- 11786205 TI - Study on the hypothalamic factors mediating the inhibitory effect of PACAP38 on ovulation. PMID- 11786206 TI - Radioiodination of the stable metabolic fragment of bradykinin, RPPGF. AB - Arg-Pro-Pro-Gly-Phe (RPPGF, BK[1-5]), is a stable metabolite of the peptide hormone bradykinin. Considering the short half-life of bradykinin (BK, approximately 15 secs), RPPGF has been used as a marker for BK's endogenous generation. A lack of a radioiodinated RPPGF has precluded the development of a radioimmunoassay for this peptide. The present study describes a two-step reaction that allows for the incorporation of 125I into the aromatic ring of the phenylalanine of RPPGF. This radioiodinated analog is recognized by an antibody to RPPGF, demonstrating its utility for the development of a radioimmunoassay for measurements of RPPGF, a stable metabolic product of bradykinin. PMID- 11786207 TI - The effect of food deprivation and experimental diabetes on orexin and NPY mRNA levels. AB - Although exogenous orexin can induce feeding, reports of increased orexin gene expression after caloric manipulations have been inconsistent. We hypothesized that orexin gene expression is increased only by extreme negative energy balance challenges. We measured hypothalamic orexin and NPY mRNA by in situ hybridization and orexin-A immunoreactivity in rats after food deprivation, streptozotocin induced diabetes, and combined deprivation and diabetes. Neither food deprivation, nor diabetes, nor the combination affected orexin mRNA levels, although orexin-A immunoreactivity was increased by diabetes. NPY mRNA levels were increased by either treatment. These results suggest that increased orexin gene expression is not a consistent correlate of negative energy balance challenges. PMID- 11786208 TI - Effects of peptides on animal and human behavior: a review of studies published in the first twenty years of the journal Peptides. AB - This review catalogs effects of peptides on various aspects of animal and human behavior as published in the journal Peptides in its first twenty years. Topics covered include: activity levels, addiction behavior, ingestive behaviors, learning and memory-based behaviors, nociceptive behaviors, social and sexual behavior, and stereotyped and other behaviors. There are separate tables for these behaviors and a short introduction for each section. PMID- 11786209 TI - Endogenous opiates: 2000. AB - This paper is the twenty-third installment of the annual review of research concerning the opiate system. It summarizes papers published during 2000 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunological responses. PMID- 11786210 TI - Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability. AB - Peptides have the potential to be potent pharmaceutical agents for the treatment of many central nervous system derived maladies. Unfortunately peptides are generally water-soluble compounds that will not enter the central nervous system, via passive diffusion, due to the existence of the blood-brain barrier. Peptides can also undergo metabolic deactivation by peptidases, thus further reducing their therapeutic benefits. In targeting peptides to the central nervous system consideration must be focused both on increasing bioavailability and enhancing brain uptake. To date multiple strategies have been examined with this focus. However, each strategy comes with its own complications and considerations. In this review we assess the strengths and weaknesses of many of the methods currently being examined to enhance peptide entry into the central nervous system. PMID- 11786211 TI - Expression of Ret receptor tyrosine kinase after transient forebrain ischemia is modulated by glial cell line-derived neurotrophic factor in rat hippocampus. AB - The Ret receptor tyrosine kinase is part of a functional receptor complex for the glial cell line-derived neurotrophic factor (GDNF) family. We examined the expression of Ret mRNA after transient forebrain ischemia, and explored the effect of local GDNF-pretreatment in rat hippocampus on Ret mRNA expression. Transient forebrain ischemia induced Ret mRNA expression in the hippocampus, with a peak effect at 12 h. Whereas intrahippocampal microinjection of GDNF (1.0 microg) in sham-operated rats induced the expression of Ret mRNA (peak at 6 to 12 h), the expected increase of Ret mRNA induced by ischemia was blunted by local GDNF-pretreatment. Immunohistochemical investigation revealed that ischemia induced Ret receptor expression in the hippocampal CA1 region was also reduced by local GDNF-pretreatment. These findings suggest that GDNF modulates the expression of Ret, and that GDNF signaling pathways that involve the Ret receptor tyrosine kinase might play an important role in brain injury induced by ischemia. PMID- 11786212 TI - Phonological processing in dyslexic children: a study combining functional imaging and event related potentials. AB - Difficulties in phonological processing are currently considered one of the major causes for dyslexia. Nine dyslexic children and eight control children were investigated using functional magnetic resonance imaging (fMRI) during non-oral reading of German words. All subjects silently read words and pronounceable non words in an event related potentials (ERP) investigation, as well. The fMRI showed a significant difference in the activation in the left inferior frontal gyrus between the dyslexic and control groups, resulting from a hyperactivation in the dyslexics. The ERP scalp distribution showed a significant distinction between the two groups concerning the topographic difference for left frontal electrodes in a time window 250-600 ms after stimulus onset for non-word reading. Both the fMRI and the ERP results support differences in phonological processing between dyslexic and normal-reading children. PMID- 11786213 TI - Glutathione potentiates cloned rat brain large conductance Ca(2+)-activated K(+) channels (rSlo). AB - We have investigated the modulation of a cloned rat brain alpha-subunit of large conductance Ca(2+)-activated K(+) channels (rSlo K(+) channels) by glutathione (GSH), a physiological sulfhydryl-specific reducing reagent. The application of GSH to the intracellular side of excised inside-out macroscopic patches of rslo transfected HEK293 cells reversibly activated the currents. The activation rate constants of the current were increased while the deactivation rate constants were decreased by GSH at all voltages tested without any change in the voltage dependence of the rate constants. GSH induced a leftward shift of the steady state conductance-voltage relationship curve of the current with no change in the slope of the curve. These results suggest that modulation by GSH may constitute an important regulatory mechanism of neuronal large conductance Ca(2+)-activated K(+) channels. PMID- 11786214 TI - Interaction between interleukin 1beta and endogenous neurokinin 1 receptor agonists in mediating plasma extravasation and neutrophil accumulation in the cutaneous microvasculature of the rat. AB - Interleukin 1beta (IL-1beta) is a potent mediator of neutrophil accumulation. Antidromic stimulation of the rat saphenous nerve leads to neurogenic oedema formation mediated by endogenous tachykinins. Here, we have investigated links between IL-1beta and the tachykinin 1 (NK(1)) receptors in microvascular events in rat skin. Saphenous nerve-induced plasma extravasation was not modulated by skin pretreatment with IL-1beta (3 pmol/site intradermally). In addition, the long-lasting antidromic electrical stimulation did not induce significant neutrophil accumulation in naive rat skin. By comparison, the effect of IL-1beta induced neutrophil accumulation was significantly potentiated by co-stimulation of the ipsilateral saphenous nerve; an effect prevented by an NK(1) receptor antagonist (SR140333, 480 nmol/kg, i.v.). We conclude that IL-1beta-induced neutrophil accumulation can be influenced in a pro-inflammatory manner by ongoing neurogenic inflammation, of relevance to the sensory nerve input that occurs during ongoing inflammatory disease. PMID- 11786215 TI - Activation of protein kinase A by nitric oxide in cultured dorsal root ganglion neurites of the rat, examined by a fluorescence probe, ARII. AB - To study the roles of nitric oxide (NO) in growth of nerve fibers, (+/-)-(E) ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamine (NOR3), an NO-donor, was applied to cultured dorsal root ganglion (DRG) neurites from a micropipette. Ejection of a small volume of 1 mM NOR3 solution (not more than 1 pl/s) from a micropipette to terminal branches of neurites caused enlargement of the neurites, and often, elongation of their growth cones. This neurite enlargement was blocked by inhibitors for soluble guanylate cyclase. The neurite enlargement did not occur when protein kinase A (PKA) was inhibited. To prove that NOR3 activated PKA, we introduced a fluorescence peptide probe, ARII that reduces its fluorescence by activated PKA, to monitor PKA activity in DRG neurites. ARII fluorescence was reduced by NOR3, which was not observed when PKA was inhibited by its specific inhibitors. These indicated that PKA was indeed activated by NO. To examine whether the PKA activation is due to inhibition of phosphodiesterase III (PDE III) by cyclic GMP, we applied PDE III-specific inhibitors and found that the inhibitions activated PKA. Since PKA regulates various neuronal functions, our finding that NO activates PKA is important to understand roles of NO in nerve fibers. PMID- 11786216 TI - Experimental herpes simplex virus encephalitis: inhibition of the expression of inducible nitric oxide synthase in mouse brain tissue. AB - In the brain tissue of 36 mice infected with herpes simplex virus type 1, strain F, we determined the expression of inducible nitric oxide synthase (iNOS) with semiquantitative reverse transcription polymerase chain reaction. The viral burden was quantitated by polymerase chain reaction. Nitric oxide, induced by iNOS, may contribute to neuronal cell damage following virus infection. As the experimental therapeutic strategy in herpes simplex virus encephalitis (HSVE), we used: N-nitro-L-arginin (L-NA), a selective inhibitor of iNOS; and combination therapies of either methylprednisolone/acyclovir or L-NA/acyclovir. The viral burden peaked in acute disease, and then returned to a low baseline value, except in untreated controls. The expression of iNOS mRNA was suppressed by L-NA and by acyclovir/corticosteroids. INOS inhibition may provide an additional therapeutic strategy targeted specifically to suppress iNOS expression as a potential secondary mechanism of tissue damage in acute and chronic HSVE. PMID- 11786217 TI - The lateral septal area is involved in mediation of immobilization stress-induced blood pressure increase in rats. AB - Immobilization stress increased the number of neurons with Fos immunoreactivity, mainly in the ventral zone of the rostral part of the lateral septal nucleus (LSV) in rats. Immobilization stress caused an increase in blood pressure, and the stress-induced pressor response was inhibited by the GABA(A) receptor agonist, muscimol (8 and 80 pmol), injected bilaterally into the rostral part of the LSV in a dose-dependent manner. Intracerebroventricular injection of muscimol (16 pmol) did not affect the immobilization stress-induced pressor response. These findings suggest that the rostral part of the LSV is involved in mediation of the stress-induced pressor response. PMID- 11786218 TI - Increased tau phosphorylation but absence of formation of neurofibrillary tangles in mice double transgenic for human tau and Alzheimer mutant (M146L) presenilin 1. AB - Neurofibrillary tangles, composed of tau proteins, are a key lesion observed in sporadic forms of Alzheimer's disease and in familial forms associated with mutations of presenilin-1 (PS1). We have generated a double transgenic mouse line expressing a human tau isoform and a mutated form of PS1 (M146L) in neurons. Increased expression of the PS1 holoprotein was observed in the tau/PS1 transgenic mice and the proteolytic fragments of PS1 did not appear to be modified. A somatodendritic accumulation of the transgenic tau and an increase in tau phosphorylation were observed in both tau- and tau/PS1 transgenic mice. Neurofibrillary tangles were not observed in animals analyzed up to 17 months. Immunoprecipitation of tau from brain homogenates demonstrated its binding with active glycogen synthase kinase-3beta in control, tau- and tau/PS1 transgenic lines. These results suggest that overexpression of this Alzheimer mutant PS1 in vivo is not by itself sufficient to induce the formation of neurofibrillary tangles, even in neurons co-expressing and accumulating a human tau isoform. PMID- 11786219 TI - Galvanic vestibular stimulation in humans produces online arm movement deviations when reaching towards memorized visual targets. AB - Using galvanic vestibular stimulation (GVS), we tested whether a change in vestibular input at the onset of goal-directed arm movements induces deviations in arm trajectory. Eight head-fixed standing subjects were instructed to reach for memorized visual targets in complete darkness. In half of the trials, randomly-selected, a 3 mA bipolar binaural galvanic stimulation of randomly alternating polarity was triggered by the movement onset. Results revealed significant GVS-induced directional shifts of reaching movements towards the anode side. The earliest significant deviations of hand path occurred 240 ms after stimulation onset. The likely goal of these online deviations of arm trajectory was to compensate for a vestibular-evoked apparent change in the spatial relationship between the target and the hand. PMID- 11786220 TI - Capsaicin sensitive afferents mediate the development of heat hyperalgesia and hindpaw edema after sciatic section in rats. AB - Sciatic section in rats evokes chronic hyperalgesia, autotomy pain behavior, and hindpaw edema, a constellation resembling complex regional pain syndrome (CRPS) in man. Glucocorticoid treatment inhibits these sequelae of sciatic section and also blocks neurogenic extravasation. Small diameter afferent neurons release substance P (SP), a mediator of both hyperalgesia and neurogenic extravasation. Now, we show that pre-emptive destruction of the small diameter fibers prevents neurogenic extravasation, and prevented the development of heat hyperalgesia and hindpaw edema after sciatic section. Thus, capsaicin sensitive primary afferent neurons which release SP are required for the development of heat hyperalgesia and hindpaw edema in this animal model of CRPS. PMID- 11786221 TI - Dipolar modelling of the scalp evoked potentials to painful contact heat stimulation of the human skin. AB - Contact heat evoked potentials (CHEPs) were collected in 12 healthy subjects by stimulating the forearm skin with a couple of thermodes at a painful intensity. The stimulated area was 628 mm(2) and the repetition rate was 0.1 Hz. The electroencephalogram was recorded by 31 electrodes placed on the scalp according to an extended 10-20 System. A dipolar model explaining the scalp CHEP distribution was built by using the brain electrical source analysis. The model includes two dipoles located bilaterally in the perisylvian region, one dipole in the deep midline region and two dipoles located bilaterally in the deep temporal lobe. This dipolar model is very similar to that previously described to explain the topography of evoked potentials to radiant heat stimulation by laser pulses. Since laser stimuli activate the nociceptive fibres, the strong similarity of the cerebral dipoles activated by contact heat stimuli and by laser pulses suggests that only nociceptive inputs are involved in the scalp painful CHEP building. Therefore, CHEP recording can be useful for clinical examination of the nociceptive system. PMID- 11786222 TI - Electric brain response to sound repetition in humans: an index of long-term memory - trace formation? AB - The developing auditory system is exposed to an almost endless variation of acoustic input in its every-day environment. All these different stimuli cannot, of course, be encoded in memory, however, at least not for any longer time. The present data suggest a principle that might be followed by the brain in selecting stimuli for the formation of longer-duration memory traces. Normal subjects ignoring auditory stimulation were presented with a randomized sequence of different sounds (simple tones in Experiment I and frequency glides in Experiment 2) with the exception that every now and then, randomly, one of the sounds was repeated in a row a few times. It was found that these repetitions elicited a novel electric brain response ('repetition negativity') which might be generated by neural activity forming these longer-duration traces. This would suggest that of all the different sounds, only those that soon occur again form more enduring memory traces (when sounds have no particular significance). PMID- 11786223 TI - Oligonucleotide lipoplexes: the influence of oligonucleotide composition on complexation. AB - Despite extensive investigations into oligonucleotide lipoplexes, virtually no work has addressed whether the physicochemical properties of these assemblies vary as a function of the constituent oligonucleotide (ODN) sequence and/or composition. The present study was aimed at answering this question. To this end, we complexed N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP) liposomes, in dispersion, with either 18-mer phosphorothiote homo oligonucleotides composed of either adenine, thymidine or cytosine; or one of three structurally related 18-mer phosphorothioate oligonucleotides (S-ODNs) (G3139, its reverse sequence and its two-base mismatch). After ODN addition to vesicles at different mole ratios, changes in pH and electrical surface potential at the lipid-water interface were analyzed by using the fluorophore heptadecyl-7 hydroxycoumarin while particle size distributions were analyzed by static-light scattering. The results indicate that each homo-oligonucleotide does indeed exhibit different complexation behavior. In particular, the maximal level of DOTAP neutralization by the polyadenine S-ODN is much lower than that for the two other homo-oligonucleotides and hence its lipoplex is much more positively charged. Much smaller electrostatic differences are also apparent between lipoplexes formed from each of the G3139-related ODNs. This paper identifies nucleotide base selection and sequence as a variable that can affect the physicochemical properties of oligonucleotide lipoplexes and hence probably their transfection competency. PMID- 11786224 TI - Oxidized low-density lipoprotein-binding specificity of Asp-hemolysin from Aspergillus fumigatus. AB - Oxidized low-density lipoprotein (Ox-LDL) is known to be involved in the generation and progression of atherosclerosis. Ox-LDL has a number of potentially atherogenic effects on vascular cells, including the uncontrolled uptake by scavenger receptors. We have previously shown that Asp-hemolysin binds to Ox-LDL in a concentration-dependent manner. The present study was undertaken to clarify the binding specificity of Asp-hemolysin to Ox-LDL. We examined the binding specificity of Asp-hemolysin to Ox-LDL using several modified lipoproteins and scavenger receptor ligands. Asp-hemolysin bound to Ox-LDL with shorter LDL oxidation times. However, Asp-hemolysin did not bind to the acetylated LDL. The native high-density lipoprotein (n-HDL) and modified HDL (e.g., acetylated HDL, oxidized HDL) also had no Asp-hemolysin binding. Furthermore, inhibitors of the scavenger receptor binding, including maleylated BSA, polyinosinic acid, dextran sulfate and fucoidin, had no effect on the binding of Ox-LDL to Asp-hemolysin. Surface plasmon resonance studies revealed that Ox-LDL binds with high affinity (K(D)=0.63 microg/ml) to Asp-hemolysin. We concluded that Asp-hemolysin is a specific binding protein with a high affinity for Ox-LDL, and its binding specificity is distinct from any receptor for Ox-LDL. The present studies suggest that Asp-hemolysin may bind to Ox-LDL using a mechanism different from the scavenger receptors. PMID- 11786225 TI - Pyridoxal 5'-phosphate inhibits DNA binding of HNF1. AB - An efficient Escherichia coli expression system was constructed for the production of a variant form of HNF1 protein having the additional five amino acid residues (Asp-Arg-Trp-Gly-Ser) at the NH(2)-terminal. The cDNA encoding HNF1 was ligated to 6 x His tag and inserted into an inducible bacterial expression vector pRSET A. After expression in E. coli, the recombinant product was purified by Ni-NTA affinity column chromatography. The purified product showed expected NH(2)-terminal sequence and specific binding to the HNF1 site. The effect of pyridoxal 5'-phosphate and its analogues on the binding activity of recombinant HNF1 was examined and found that only pyridoxal 5'-phosphate effectively inhibited the DNA binding. The concentration of pyridoxal 5'-phosphate that inhibited 50% of DNA binding was around 100 microM. Furthermore, we identified Lys197 of HNF1 molecule as the essential residue of DNA binding. These observations suggest that pyridoxal 5'-phosphate directly interacts with tissue specific transcription factor HNF1 and modulates the binding to DNA. PMID- 11786226 TI - The binding of lactoferrin to glycosaminoglycans on enterocyte-like HT29-18-C1 cells is mediated through basic residues located in the N-terminus. AB - Although lactoferrins (Lfs) isolated from milk of various mammals exhibit a close structural relationship, they show species-specific binding to cells. To define the specificity of recognition of human (hLf), bovine (bLf) and murine (mLf) lactoferrin by human intestinal cells, we analysed the binding of the three proteins to a subclone derived from human carcinoma cell line HT29. We observed that hLf and bLf interact with two types of binding sites (K(d): 63+/-22 nM; 0.7+/-0.2 microM) while mLf was recognized only by the lowest affinity binding sites with a lower number of binding sites. Using N-terminal deleted human Lf variants, we found that the sequence G(1)RRRR(5) is mainly responsible for the interactions with HT29 cells. Lactoferrin-binding sites on the surface of HT29 cells were further identified as heparan sulphate and chondroitin sulphate glycosaminoglycans. We conclude that the presence of the sequence A(1)PRK(4) in bLf and K(1)ATT(4) in mLf provides an insight into why the interaction of bLf with cell membrane-associated glycosaminoglycans is similar to that of hLf and why binding of these lactoferrin species differs from that of murine Lf. PMID- 11786227 TI - Exploring computational lead optimisation with affinity constants obtained by surface plasmon resonance for the interaction of PorA epitope peptides with antibody against Neisseria meningitidis. AB - LUDI is a program used for de novo structure-based design of ligands and can predict binding of ligands quantitatively using a scoring function. Here we evaluate LUDI in a lead optimisation study with ligands for the antibody MN12H2, that has been raised against outer membrane protein PorA epitope P1.16 of Neisseria meningitidis. The ligands were synthetic peptides that are derived from the smallest binding epitope (182)DTNNN(186). LUDI's fragment building rules are used for the proposal of new peptide-ligands for MN12H2 and were focused on replacements of Asp(186) in the epitope. Accordingly, a series of peptides was synthesised with isosteric mutations. The interaction of the peptides with MN12H2 was analysed with a surface plasmon resonance competition assay yielding equilibrium binding constants in solution (K(S)). The binding affinity seems to be largely determined by entropy, and the side chain of Asn(186) is sensitive for charge, inversion, hydrophobicity and size. Head-to-tail cyclisation of the peptide in a nine-amino-acid ring gives little reduction in affinity. It is concluded that the scoring function of LUDI does not help in optimisation of the peptide lead for MN12H2 binding. Other more elaborate molecular mechanics calculations show similar results. This implies that our current knowledge of molecular recognition is insufficient for explaining a case of peptide-protein binding, where the design process requires subtle changes in structure (from lead finding to lead optimisation). PMID- 11786228 TI - Proteolytic cleavage of inducible nitric oxide synthase (iNOS) by calpain I. AB - Proteolytic degradation of inducible nitric oxide synthase (iNOS or NOS2; EC 1.14.13.39) is one of the key steps by which the synthetic glucocorticoid dexamethasone controls the amount of iNOS protein and thus the production of nitric oxide (NO) in interferon-gamma-stimulated RAW 264.7 cells. In the present study we examined the role of the calmodulin (CaM)-binding site present within iNOS protein for the proteolytic degradation by the calcium-dependent neutral cysteine protease calpain I (EC 3.4.22.17). Using pulse chase experiments as well as cell-free degradation assays we show that the iNOS monomer is a direct substrate for cleavage by calpain I. Two structural determinants are involved in proteolytic cleavage, the canonical CaM-binding domain present at amino acids 501 532 and a conformational determinant located within iNOS. The access of the CaM binding region appears to be critical for substrate cleavage as incubation of in vitro synthesized iNOS with purified CaM inhibits iNOS degradation by calpain I. Moreover, cytosolic CaM levels are decreased upon treatment of RAW 264.7 cells with dexamethasone as assessed by immunoprecipitation. The data shown herein provide novel insights into the underlying mechanisms involved in the anti inflammatory actions of glucocorticoids. PMID- 11786229 TI - NMR investigations of protein-carbohydrate interactions: insights into the topology of the bound conformation of a lactose isomer and beta-galactosyl xyloses to mistletoe lectin and galectin-1. AB - A hallmark of oligosaccharides is their often limited spatial flexibility, allowing them to access a distinct set of conformers in solution. Viewing each individual or even the complete ensemble of conformations as potential binding partner(s) for lectins in protein-carbohydrate interactions, it is pertinent to address the question on the characteristics of bound state conformation(s) in solution. Also, it is possible that entering the lectin's binding site distorts the low-energy topology of a glycosidic linkage. As a step to delineate the strategy of ligand selection for galactosides, a common physiological docking point, we have performed a NMR study on two non-homologous lectins showing identical monosaccharide specificity. Thus, the conformation of lactose analogues bound to bovine heart galectin-1 and to mistletoe lectin in solution has been determined by transferred nuclear Overhauser effect measurements. It is demonstrated that the lectins select the syn conformation of lactose and various structural analogues (Galbeta(1-->4)Xyl, Galbeta(1-->3)Xyl, Galbeta(1-->2)Xyl, and Galbeta(1-->3)Glc) from the ensemble of presented conformations. No evidence for conformational distortion was obtained. Docking of the analogues to the modeled binding sites furnishes explanations, in structural terms, for exclusive recognition of the syn conformer despite the non-homologous design of the binding sites. PMID- 11786230 TI - Regulation of glutamine synthetase by metal-catalyzed oxidative modification in the marine oxyphotobacterium Prochlorococcus. AB - The inactivation of glutamine synthetase (GS; EC 6.3.1.2) by metal-catalyzed oxidation (MCO) systems was studied in several Prochlorococcus strains, including the axenic PCC 9511. GS was inactivated in the presence of various oxidative systems, either enzymatic (as NAD(P)H+NAD(P)H-oxidase+Fe(3+)+O(2)) or non enzymatic (as ascorbate+Fe(3+)+O(2)). This process required the presence of oxygen and a metal cation, and is prevented under anaerobic conditions. Catalase and peroxidase, but not superoxide dismutase, effectively protected the enzyme against inactivation, suggesting that hydrogen peroxide mediates this mechanism, although it is not directly responsible for the reaction. Addition of azide (an inhibitor of both catalase and peroxidase) to the MCO systems enhanced the inactivation. Different thiols induced the inactivation of the enzyme, even in the absence of added metals. However, this inactivation could not be reverted by addition of strong oxidants, as hydrogen peroxide or oxidized glutathione. After studying the effect of addition of the physiological substrates and products of GS on the inactivation mechanism, we could detect a protective effect in the case of inorganic phosphate and glutamine. Immunochemical determinations showed that the concentration of GS protein significantly decreased by effect of the MCO systems, indicating that inactivation precedes the degradation of the enzyme. PMID- 11786231 TI - Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver slices: effects on cellular metabolism and drug biotransformation. AB - Cultured rat precision-cut liver slices (PCLS) were used to study the influence of hypothermic preservation and reoxygenation at 37 degrees C on cellular metabolism and drug biotransformation. Cold hypoxic storage caused a depressed metabolism in rat liver slices, but reoxygenation for 8 h at 37 degrees C partially restored the levels of both ATP and GSH and totally restored the capacity to synthesize proteins. Metabolism of midazolam (CYP3A-dependent oxidation) by cold preserved liver slices was decreased by 30% but no further affected by reoxygenation, showing the same profile as freshly cut slices. Such a reoxygenation at 37 degrees C is accompanied by a dramatic loss of CYP3A2 protein while CYP3A1 protein was unaffected. These results suggest that CYP3A2 did not play a major role in midazolam oxidation. Such results are not consistent with a putative reoxygenation injury but rather with cold hypoxic damage. Since cold preserved liver slices did not respond to bacterial endotoxin stimulation (lipopolysaccharides), a minor role of non-parenchymal cells is suggested as mediators for deleterious effects developed during the cold storage. PMID- 11786232 TI - Nitric oxide binding to oxygenated hemoglobin under physiological conditions. AB - We have added nitric oxide (NO) to hemoglobin in 0.1 M and 0.01 M phosphate buffers as well as to whole blood, all as a function of hemoglobin oxygen saturation. We found that in all these conditions, the amount of nitrosyl hemoglobin (HbNO) formed follows a model where the rates of HbNO formation and methemoglobin (metHb) formation (via hemoglobin oxidation) are independent of oxygen saturation. These results contradict those of an earlier report where, at least in 0.01 M phosphate, an elevated amount of HbNO was formed at high oxygen saturations. A radical rethink of the reaction of oxyhemoglobin with NO under physiological conditions was called for based on this previous proposition that the primary product is HbNO rather than metHb and nitrate. Our results indicate that no such radical rethink is called for. PMID- 11786233 TI - Neural transplantation therapy for Parkinson's disease: potential and pitfalls. PMID- 11786234 TI - Frequency coding of positional information by an identified neuron, the AP cell, in the leech, Whitmania pigra. AB - The synaptic connections from pressure-sensitive receptors (P cells) to identified neurons of unknown function (known as anterior pagoda or AP cells) were used to study the way in which leeches process information about the position of a mechanical stimulus on its skin. We elicited spikes in P cells by injecting current intracellularly while recording from AP neurons. The postsynaptic responses consisted of an increase in impulse frequency. We show here that the AP neuron can encode positional information in terms of the frequency of its action potentials. Thus, the AP neuron can serve as an indicator of integrative mechanisms used in the processing of sensory information that is important for the behavior of the animal. PMID- 11786235 TI - Tetra-butyl ammonium attenuates evoked release of acetylcholine from mouse hemidiaphragm preparation. AB - Tetra-butyl ammonium is a homologous member of mono-quaternary ammonium salts, and it has been reported to have a property of nondepolarizing neuromuscular relaxant. However, no neurochemical evidences exist that tetra-butyl ammonium may interfere with quantal release of acetylcholine from motor nerve terminals. In this study, using the neurochemical method, we investigated the effect of tetra butyl ammonium on stimulation-evoked release of acetylcholine from mouse hemidiaphragm preparation. The preparation was loaded with [3H]choline (5 microCi/ml). Low concentrations of tetra-butyl ammonium (10(-5) M) had no effects. On the other hand, at concentrations of 4x10(-5) and 10(-4) M, this compound significantly reduced the [Ca2+]o-dependent release of acetylcholine from phrenic nerves. This finding indicates that tetra-butyl ammonium possesses a presynaptic inhibitory effect on acetylcholine release from the phrenic nerve terminal. PMID- 11786236 TI - Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices. AB - Using in vitro superfusion techniques and electrical field stimulation, a volatile anesthetic, halothane, decreased impulse-dependent vesicular release, but did not affect amphetamine-induced cytoplasmic release of dopamine (DA) from the rat striatal slice preparations loaded with [3H]-DA. Contrary to previous in vivo studies, halothane at concentrations applied (1% to 4%) did not enhance the release of DA from slice preparation in which the cell bodies were absent, and therefore, the possible site of action was located on the axon terminals. In this in vitro experiment, halothane decreased the fractional release of DA in a concentration-dependent manner and attenuated the increase of impulse-dependent DA release when amphetamine or nomifensine administration was combined with electrical stimulation. D2-receptor agonists (quinpirole and apomorphine) reduced the release, and antagonists (sulpiride and haloperidol) enhanced the release of DA. In the presence of halothane, D2-receptor antagonists had no effect on DA release. It is concluded that halothane may have some modulatory effect on D2 receptor mediated presynaptic control of DA release. PMID- 11786237 TI - hNT neurons delay onset of motor deficits in a model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that manifests as a progressive muscular weakness leading to paralysis and death. Because of the diffuse nature of the motor neuron death, this disease is not considered a good candidate for treatment through neural transplantation. The purpose of this study was to show that transplantation of human neuron-like cells (hNT neurons) into the spinal cord of a transgenic ALS mouse model would improve motor deficits. The hNT neurons were transplanted bilaterally into L4-L5 spinal cord of the transgenic mice ( approximately 8 weeks of age), and the animals were evaluated on health and behavioral measures. The animals were perfused, and immunohistochemistry was performed to identify the transplanted cells. Transplantation of the hNT neurons into the spinal cord delayed the onset of motor behavioral symptoms. This was the first demonstration that even localized transplantation of neural cells directly into the parenchyma could improve motor function in an ALS model. Further study is needed to delineate the mechanism underlying these effects. This therapeutic approach has the potential to restore neural transmission, thereby improving quality of life for the ALS patient and possibly extend life expectancy. PMID- 11786238 TI - 2-buten-4-olide, an endogenous feeding suppressant, improves spatial performance through brain acidic fibroblast growth factor in mice. AB - Endogenous sugar acid 2-buten-4-olide, a satiety substance, has been shown to increase the blood glucose, norepinephrine, and glucocorticoid concentrations that are known to modulate learning and memory processes. The glucose-induced release of acidic fibroblast growth factor facilitated the hippocampus-dependent memory function. In the present study, we investigated the effect of 2-buten-4 olide on the spatial performance of male DDY mice undergoing the water maze task. The intraperitoneal injection of 2-buten-4-olide (5 mg/kg) facilitated the spatial performance, which was indicated by a reduction in the escape latency in which the mouse finds and climbs the goal platform in comparison to the vehicle injected control mice. In the probe test after removing the platform, the 2-buten 4-olide-treated mice stayed a longer time in the quadrant where the platform was originally located and crossed more frequently at the platform location than did the control mice. The pretreatment of acidic fibroblast growth factor antibody injected into the lateral ventricle eliminated the effect of 2-buten-4-olide both during the training sessions and during the probe test. Therefore, 2-buten-4 olide was found to improve the spatial performance, and this effect is mediated, at least in part, by acidic fibroblast growth factor. PMID- 11786239 TI - The effect of naloxone on operant behavior for food reinforcers in DBA/2 mice. AB - Mice are powerful models to investigate the genetic basis of food reward because many spontaneous obesity mutants exist and the murine genome is accessible to selectively targeted manipulations. Experiments in rats have shown that opioid receptor blockade reduces operant responding to food reinforcers. The present study investigated whether DBA/2J mice would display similar behavior in response to an opioid antagonist. Twelve male DBA/2J mice were trained to lever press for food reinforcers and subsequently randomized in a within subjects design for no injection, saline injection, or 10 mg/kg naloxone injection intraperitoneal (i.p.) 20 min before each daily trial under ad lib or food-deprived conditions. A significant main effect of injection occurred to reduce lever pressing by the mice. However, a greater pharmacological effect of naloxone occurred compared with saline on the operant responding only under the food-deprived conditions. Interestingly, the percentage of dispensed food pellets actually consumed was significantly reduced after naloxone injection compared with saline injection for either chow-based or sucrose pellets under ad lib or deprived feeding conditions. These data suggest that opioids specifically influence consumatory behavior in mice, but our findings on instrumental behavior were confounded by an independent inhibitory effect of an i.p. saline injection. PMID- 11786240 TI - Central discriminative effects of morphine in rats: training via intracerebroventricular administration. AB - There have been studies of the discriminative effects of intracerebroventricularly (ICV)-administered morphine (MOR) in rats trained to discriminate MOR systemically, but the converse has not been done. In this study, rats were trained to discriminate between ICV (1-10 microg/3 microl, 1 h) or subcutaneous (SC) (3.0 mg/kg, 30 min) injections of MOR vs. saline/vehicle in a discrete-trial avoidance/escape procedure. On generalization testing, subjects in both the ICV- and SC-trained groups responded on the MOR-appropriate lever at ICV MOR doses < or =1-3 microg, and at SC MOR doses 2 to 3 orders of magnitude higher (vs. ICV). Naltrexone (SC) blocked the stimulus effects of MOR (ICV) equipotently in both training groups. In ICV-trained subjects, levorphanol (SC), the mu-opioid selective peptide [D-Ala2, NMePhe4, Gly-ol]-enkephalin (DAMGO) (ICV), and the enkephalinase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta alanine (SCH 32615) (ICV) produced complete MOR-appropriate responding, whereas the dextrorotary enantiomer of levorphanol dextrorphan (SC; < or = 3.0 mg/kg) and the delta-opioid selective peptide [D-Pen2, D-Pen5]-enkephalin (DPDPE) (ICV, < or = 0.03 mg) did not. SC-trained subjects did not generalize to SCH 32615, which suggests qualitative differences in the discriminative stimulus effects of novel drugs as a function of the route of administration of the training drug. These data demonstrate that it is feasible to train rats to discriminate an opioid administered by the ICV route, and to perform extended tests of generalization to novel drugs (SC or ICV) in rats so trained. PMID- 11786241 TI - Gender differences in spontaneous and MK-801-induced activity after striatal lesions. AB - At different times post-lesion, the excitotoxically lesioned striatum has been shown to undergo significant neuroanatomical and neurochemical changes, which could be expressed behaviorally. Gender and dose of excitotoxin are other variables that may modify the behavioral effects of the lesion. Consequently, the purpose of this study was to determine the effect of dose, gender, and time post lesion on spontaneous and drug-induced locomotor behavior after intrastriatal KA lesions. Results showed that dose and time post-lesion had a significant effect on the deficits observed. Hyperactivity induced by the lesion with KA (5 nm) subsided as time post-lesion increased. Both the pattern of spontaneous and MK 801-induced locomotor activity were different for male and female rats. In female animals with KA lesions (5 nm), MK-801 did not stimulate ambulatory activity nor reduce vertical activity. Both female and male rats lesioned with KA (5 nm) showed an exaggerated response to amphetamine, at a time when spontaneous locomotor activity was reduced to control levels. Haloperidol significantly reduced locomotor activity in all groups. PMID- 11786242 TI - Endomorphin1-like immunoreactivity in the limbic system of Syrian hamsters (Mesocricetus auratus). AB - Recently, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2; EM1), an endogenous peptide that has high affinity and selectivity for the mu-opiate receptor, has been shown to modulate emotional behavior in mice and social behavior in Syrian hamsters. Endomorphin-1 (EM1) is present throughout the central nervous system in rats, mice, and guinea pigs; however, the distribution of EM1 in hamsters has not been described. The purpose of the present study was to investigate the distribution of EM1-like immunoreactivity (EM1L-IR) in the limbic system of Syrian hamsters using immunocytochemistry. Perikarya containing EM1L-IR were present in the anterior area, dorsomedial, ventromedial, periventricular, posterior, and arcuate nuclei of the hypothalamus. Fibers expressing EM1L-IR were present in the nucleus accumbens, caudate putamen, septum, bed nucleus of the stria terminalis, amygdaloid complex, and hypothalamus. The distribution of EM1 suggests a potential endogenous role for this peptide in major processes modulated by opiates, including affective states and social behavior. PMID- 11786243 TI - Angiotensin receptor blockade in the anterior hypothalamic area inhibits stress induced pressor responses in rats. AB - Central angiotensin systems are involved in expression of pressor responses induced by immobilization stress. In this study, we examined whether angiotensin receptors in the anterior hypothalamic area are involved in the pressor response during stress exposure in rats. Intracerebroventricular injections of the angiotensin AT1-receptor antagonist losartan (6.5 and 22 nmol) attenuated pressor responses to immobilization stress dose-dependently. Injections of losartan (0.065 and 0.22 nmol) into the anterior hypothalamic area also suppressed the stress-induced pressor response dose-dependently, whereas intraventricular injection of losartan (2.2 nmol) did not affect it. Immobilization stress caused increases in plasma catecholamine levels. The stress-induced increase of plasma catecholamine levels was also inhibited by angiotensin receptor blockade in the anterior hypothalamic area. The present results suggest that angiotensin receptors in the anterior hypothalamic area are involved in expression of the pressor response and sympathetic activation induced by immobilization stress. PMID- 11786244 TI - The effects of Zn2+ on long-term potentiation of C fiber-evoked potentials in the rat spinal dorsal horn. AB - Tetanic stimuli of peripheral C fibers produces long-term potentiation (LTP) in the spinal cord, which may contribute to sensitization of spinal pain-sensitive neurons. Zn2+ is widely distributed in the central nervous system and has blocked (LTP) in the hippocampus. The present study examined the effects of Zn2+ on the induction and maintenance of C fiber-evoked LTP in the deep dorsal horn of spinalized rats in vivo. The sciatic nerve was stimulated by tetanic stimuli for inducing LTP. (1) Topical administration of Zinc chloride (15 microM) to the spinal cord 15 min before tetanic stimulation completely blocked the induction of LTP, but not the baseline C responses. When Zn2+ was given 2 h after induction of LTP, no significant effect occurred. (2) Chelation of Zn2+ by disodium calcium ethylene diaminetelraacetate (CaEDTA) (500 microM) resulted in no effect on LTP. (3) Coadministration of Zn2+ (15 microM) and N-methyl-D-aspartic acid (NMDA) (5 microM) significantly attenuated C fiber-evoked potentials, which was prevented by the NMDA receptor antagonist AP-5 (100 microM). The present results showed that Zn2+ may contribute to the modulation of the formation, but not the maintenance, of spinal LTP. NMDA receptors may be involved in Zn2+-induced modulation. PMID- 11786245 TI - Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer's disease. AB - Beta-amyloid (Abeta) plaques have been shown to induce inflammatory changes in Alzheimer's disease brains. Cortical, but not cerebellar tissue from 16-month-old Tg2576 (Tg+) mice showed significant increases in interleukin (IL)-1alpha (2.2 fold), IL-1beta (3.4-fold), tumor necrosis factor-alpha (3.9-fold), and monocyte chemoattractant protein-1 (2.5-fold) mRNA levels compared to controls (Tg-). These changes were not apparent in 6-month-old Tg+ mice except for TNF-alpha. mRNA levels of glial fibrillary acidic protein and complement components, C1qA and C3 were also elevated in aged mice. Lipopolysaccharide (LPS) (25 microg/mouse, i.v.) induced a significantly greater production of IL-1beta protein in the cortices and hippocampi of Tg+ vs. Tg- mice at 1, 2, 4, and 6 h. Experiments in 6-month-old mice showed that not only was there less cytokine produced compared to 16-month-old mice, but the exacerbated cytokine response to LPS in Tg+ mice was not apparent. Higher levels of Abeta1-40 were measured in the cortices of 6- and 16-month-old Tg+ mice at 4-6 h after LPS, which returned to baseline after 18 h. We demonstrate that Abeta plaques elicit inflammatory responses in Tg2576 mice that are further exacerbated when challenged by an exogenous inflammatory insult, which may serve to amplify degenerative processes. PMID- 11786246 TI - Effect of adrenalectomy and dexamethasone treatment on prolactin secretion of lactating rats. AB - The contribution of corticosteroids to the control of prolactin secretion in lactating rats was investigated. The prolactin response to domperidone (20 microg/kg b.w., i.v.), a dopamine receptor antagonist and to domperidone plus formalin stress was tested in adrenalectomized and/or dexamethasone-treated continuously nursing rats. Animals were adrenalectomized on the 3rd day of lactation and tested on the 7th day of lactation. Dexamethasone was injected s.c. 24 h before testing (400 microg/kg b.w.) and on the day of testing (200 microg/kg b.w.). Domperidone caused a significant rise in plasma prolactin levels. The prolactin response to domperidone was twice as high in solely adrenalectomized dams and in solely dexamethasone-treated rats compared to controls. In adrenalectomized animals treated with dexamethasone, the prolactin response to domperidone was like in controls. Formalin injection to either adrenalectomized plus domperidone-treated animals or to animals injected with dexamethasone plus domperidone, resulted in a statistically significant depletion of plasma prolactin. In controls and in adrenalectomized animals receiving dexamethasone and domperidone, the prolactin response to formalin was very similar, i.e., plasma prolactin levels did not change after the administration of formalin. The present findings suggest that in lactating rats, corticosteroids are involved in the prolactin response to domperidone and to formalin stress. PMID- 11786247 TI - Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study. AB - We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed. PMID- 11786248 TI - The effects of excitotoxic lesions of the pedunculopontine tegmental nucleus on conditioned place preference to 4%, 12% and 20% sucrose solutions. AB - A number of studies have suggested that the pedunculopontine tegmental nucleus (PPTg) may play a role in reward-related behaviour. The present study was intended to investigate this further using conditioned place preference. In conditioned place preference paradigms the amount of time spent in a preferred environment is proportional to the value of the reinforcement present, until a maximum is reached. In the present experiments we aimed to determine whether this relationship was affected by lesions of the PPTg by examining the formation of a conditioned place preference to either 4%, 12% or 20% sucrose solutions in food deprived PPTg lesioned rats. The conditioned place preference apparatus had two compartments different in colour, smell and floor texture. During conditioning, rats were restricted to one compartment or the other, one of which was paired with sucrose. This was carried out during 30 min sessions, alternating conditioned or nonconditioned trials for 14 days. On the test day, rats were given access to both compartments through a connecting chamber, and were scored for side preference over 15 min. Both PPTg and sham lesioned rats showed a conditioned place preference to 12% and 20% sucrose, but no place preference was formed by either group to 4% sucrose. There was no significant difference between the groups in the place preference shown. Consumption of 4% sucrose was not affected by excitotoxic lesions of the PPTg, but PPTg lesioned rats consumed significantly more 12% and 20% sucrose than sham controls. This suggests that perception of reward value, as judged by CPP formation, is unchanged by excitotoxic lesions of the PPTg. The increased consumption of 12% and 20% sucrose shown by rats bearing such lesions is therefore not likely to be a product of altered reward perception. PMID- 11786249 TI - Protein kinases and protein phosphatases in prokaryotes: a genomic perspective. AB - For many years, the regulation of protein structure and function by phosphorylation and dephosphorylation was considered a relatively recent invention that arose independently in each phylogenetic domain. Over time, however, incidents of apparent domain trespass involving the presence of 'eukaryotic' protein kinases or protein phosphatases in prokaryotic organisms were reported with increasing frequency. Today, genomics has provided the means to examine the phylogenetic distribution of 'eukaryotic' protein kinases and protein phosphatases in a comprehensive and systematic manner. The results of these genome searches challenge previous conceptions concerning the origins and evolution of this versatile regulatory mechanism. PMID- 11786250 TI - Current status of defensins and their role in innate and adaptive immunity. AB - Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants. Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization. A large volume of literature is available on defensins' occurrence, structural characterization, gene expression and regulation under normal and pathological conditions. Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions. In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators. PMID- 11786251 TI - The Escherichia coli ftsK1 mutation attenuates the induction of sigma(S) dependent genes upon transition to stationary phase. AB - A mutation in the cell division gene ftsK causes super-induction of sigma(70) dependent stress defense genes, such as uspA, during entry of cells into stationary phase. In contrast, we report here that stationary phase induction of sigma(S)-dependent genes, uspB and cfa, is attenuated and that sigma(S) accumulates at a lower rate in ftsK1 cells. Ectopic overexpression of rpoS restored induction of the rpoS regulon in the ftsK mutant, as did a deletion in the recA gene. Thus, a mutation in the cell division gene, ftsK, uncouples the otherwise coordinated induction of sigma(S)-dependent genes and the universal stress response gene, uspA, during entry into stationary phase. PMID- 11786252 TI - Studies on the production of quorum-sensing signal molecules in Mannheimia haemolytica A1 and other Pasteurellaceae species. AB - The bioluminescence assay system using Vibrio harveyi reporter strains were used to examine quorum-sensing autoinducer (AI) activity from Mannheimia haemolytica A1 cell-free culture supernatant. We showed that M. haemolytica A1 cell-free culture supernatant contains molecules that can stimulate the quorum-sensing system that regulates the expression of the luciferase operon in V. harveyi. Specifically, M. haemolytica A1 can stimulate only the quorum system 2 but not system 1, suggesting that the culture supernatant only contains molecules similar to AI-2 of V. harveyi. The bioluminescence assay was also used to show that culture supernatants from related Pasteurellaceae organisms, Pasteurella multocida, Pasteurella trehalosi, Actinobacillus suis and Actinobacillus pleuropneumoniae, also contain AI-2-like molecules. This is consistent with the presence of a luxS homolog in the genomes of P. multocida and A. pleuropneumoniae. A luxS homolog was cloned by PCR from M. haemolytica A1 using sequencing data from the ongoing genome sequencing project. The cloned luxS(M.h.) was able to complement AI-2 production in the Escherichia coli DH5alpha luxS mutant. This is the first report of a quorum-sensing activity in M. haemolytica A1 and suggests that this bacterium utilizes this mechanism to regulate expression of genes under specific conditions. PMID- 11786253 TI - Lactobacilli express cell surface proteins which mediate binding of immobilized collagen and fibronectin. AB - Binding of immobilized collagen-I (Cn-I) and fibronectin (Fn) by Lactobacillus acidophilus CRL 639 depends on cell-surface proteins. Capsule formation during the stationary growth phase has a negative effect on adherence of Cn-I and Fn. However, cells from the exponential growth phase, which produce no capsule, exhibit maximal binding. Binding is sensitive to trypsin, proteinase K, pronase E, and heat. Gelatin and soluble Cn-I partially inhibit binding of Cn-I although various proteins, sugars and amino acids do not affect binding to Fn. These results indicate that protein-protein interactions mediate adhesion to extracellular matrix proteins. SDS-PAGE and Western blot analyses of surface proteins revealed that several proteins including the major 43-kDa protein of the S-layer are expressed. Monoclonal antibodies showed that Fn binds to a 15-kDa protein, while Cn-I binds to proteins of 45 and 58 kDa. PMID- 11786254 TI - In vitro co-culture of two AMF isolates Gigaspora margarita and Glomus intraradices on Ri T-DNA transformed roots. AB - An in vitro system using Ri T-DNA transformed carrot roots as the host bearing simultaneously different arbuscular mycorrhizal (AM) fungi belonging to two genera Glomus intraradices (Smith and Schenck) and Gigaspora margarita (Becker and Hall) was developed. Co-existence appeared healthy and harmonious, as both the generic species showed extensive hyphal proliferation and sporulation. The co culture model under the in vitro system appears especially appropriate for further investigations on the competition and on the interaction mechanism involved in such types of associations occurring in nature and also as a model approach towards mass production of multiple mycorrhizal fungal isolates. This is a first report of successful co-culture of two genera of AM fungi under in vitro conditions. PMID- 11786255 TI - Presence of organic sources of nitrogen is critical for filament formation and pH dependent morphogenesis in Yarrowia lipolytica. AB - Yeast dimorphism is an attractive model for the study of cell morphogenesis and differentiation. The non-conventional yeast Yarrowia lipolytica was chosen to characterise the regulation of dimorphic transition by extracellular pH and by the presence of organic sources of nitrogen. Organic nitrogen sources appear to be required for the morphogenic effect of pH. Two sets of mutants defective in either pH-dependent or nitrogen source-dependent signalling pathway were analysed. The results suggest that the latter but not the former is required for both normal filament formation on solid medium and pH-dependent dimorphic behaviour of Y. lipolytica in liquid medium. We propose that in this organism pH affects the formation of hyphae indirectly by modulation of availability and/or utilisation of transportable sources of nitrogen. PMID- 11786256 TI - Isolation of a Pseudomonas monteilli strain with a novel phosphotriesterase. AB - A Pseudomonas monteilli strain (designated C11) that uses the phosphotriester coroxon as its sole phosphorus source has been isolated. Native PAGE and activity staining identified a single isozyme with significant phosphotriesterase activity in the soluble fraction of the cell. This phosphotriesterase could hydrolyse both coumaphos and coroxon. The hydrolysis product of coroxon, diethylphosphate, and the thion analogue, coumaphos, could not serve as phosphorus sources when added to the growth medium. The majority of the phosphotriesterase and phosphatase activity was contained in the soluble fraction of the cell. Phosphatase activity was inhibited by vanadate as well as by dialysis against the metal chelator, EDTA. Phosphotriesterase activity was not affected by either vanadate or dialysis with EDTA or 1,10-phenanthroline. Phosphotriesterase activity was regulated by the amounts of both phosphate and coroxon in the medium, whereas total phosphatase activity was regulated by phosphate but not coroxon. A lack of hybridisation using a probe against the opd (organophosphate degradation) gene encoding a phosphotriesterase from Flavobacterium sp. ATCC27551 against bulk DNA from P. monteilli C11 suggested that this strain does not contain opd. The work presented here indicates the presence of a novel phosphotriesterase in P. monteilli C11. PMID- 11786257 TI - Observation of EGFP-visualized nuclei and distribution of vacuoles in Aspergillus oryzae arpA null mutant. AB - The arpA gene encoding Arp1 (actin-related protein) was previously cloned and characterized from Aspergillus oryzae. Phenotypes of the arpA null mutant indicate its requirement for normal nuclear distribution and morphology of conidiophores. In this study, we further characterized the function of the arpA gene in distribution of organelles. For further analysis of nuclear migration in living cells, an expression system consisting of a fusion protein of Aspergillus nidulans histone H2B and EGFP (H2B::EGFP) was used. This demonstrated diminished hyphal-tip growth rate and inefficient nuclear transport to apical regions in the arpA null mutant. Expression of H2B::EGFP also revealed an increase in the nuclear number of each conidium in the arpA null mutant, implicating a role for the arpA gene in controlling the nuclear movement into conidia. Furthermore, staining of vacuoles of the arpA null mutant with CMAC (cell tracker blue) suggested that the arpA gene is required for proper vacuolar distribution in addition to its role in normal nuclear distribution. PMID- 11786258 TI - Isolation of a novel, phosphate-activated glutaminase from Bacillus pasteurii. AB - In Bacillus pasteurii glutamine is being taken up efficiently by a sodium dependent uptake system and subsequently hydrolysed to ammonium and glutamate. Concerning the latter process, a catabolic L-glutamine amidohydrolase (glutaminase) was isolated from the cytoplasm of this alkaliphilic bacterium and purified to homogeneity using liquid chromatography. Biochemical and physical parameters of the pure enzyme were examined in detail. Interestingly, analysis of the glutaminase revealed a marked increase in catalytic activity in the presence of phosphate, a property yet restricted to animal glutaminases. This is the first report on the presence of a phosphate-activated glutaminase in bacteria. PMID- 11786259 TI - Copper and cadmium increase laccase activity in Pleurotus ostreatus. AB - Addition of copper (0.5-5 mM) or cadmium (1-5 mM) to the white rot fungus Pleurotus ostreatus cultivated in liquid nitrogen-limited medium for 12 days increased the activity of laccase. The addition of 2 mM Cd led to an 18.5-fold increase of activity, 1 mM Cu increased the activity eight-fold. When added earlier than 12 days, the activation of laccase was delayed (Cu) or decreased (Cd). Ag, Hg, Pb, Zn, and H(2)O(2) decreased laccase activity. To study the effect on native enzymes, purified laccase was incubated with Cd, Cu, and Hg. The addition of Hg decreased the activity of laccase immediately and reduced the temporal stability of the enzyme, while the addition of Cu (0.05-50 mM) increased both enzyme activity and stability. Laccase extracted at different stages of straw colonisation differed in its response to heavy metals. PMID- 11786260 TI - The triazine hydrolase gene trzN from Nocardioides sp. strain C190: cloning and construction of gene-specific primers. AB - Using oligonucleotides derived from the N-terminal sequence of a triazine hydrolase from Nocardioides sp. strain C190, two DNA fragments containing trzN were cloned into Escherichia coli and their nucleotide sequences were determined. The 456-amino acid polypeptide predicted from the 1356-bp trzN ORF displayed significant similarity to triazine hydrolases from Pseudomonas and Rhodococcus isolates and belonged to the same amidohydrolase family. The trzN gene was flanked by two DNA sequences possessing 57 and 69% identity, respectively, at the protein level to Rhodococcus erythropolis sequences for a transposase and a transposase helper protein. Amplification primers specific to trzN were tested in soils inoculated with strain C190. The results demonstrated that the primers were specific to trzN, and could detect populations at 10(8) cfu g(-1) soil using 250 mg soil samples. PMID- 11786261 TI - The C-terminal portion of the fibrinogen-binding protein of Streptococcus equi subsp. equi contains extensive alpha-helical coiled-coil structure and contributes to thermal stability. AB - The major cell wall-associated protein of the equine pathogen Streptococcus equi subsp. equi is a fibrinogen-binding protein (FgBP) which binds horse fibrinogen and equine IgG-Fc avidly through residues located in the N-terminal half and central regions of the molecule, respectively. The molecule is a major virulence factor for the organism and displays protective potential. In the present study, we use circular dichroism spectroscopy to investigate the secondary structure of the protein and show through the analysis of a panel of recombinant FgBP truncates that the C-terminal portion of FgBP contains an extensive alpha-helical coiled-coil structure that contributes to the thermal stability of the molecule. PMID- 11786262 TI - A recombinase A-deficient strain of Actinobacillus actinomycetemcomitans constructed by insertional mutagenesis using a mobilizable plasmid. AB - The gene coding for recA in the oral pathogen Actinobacillus actinomycetemcomitans SUNY 465 was cloned and sequenced. The DNA sequence coded for a 352-amino acid protein that was homologous to RecA of a variety of bacterial species. A derivative of a non-replicating mobilizable plasmid was constructed for directed mutagenesis in A. actinomycetemcomitans. A recA deficient strain of A. actinomycetemcomitans was developed by homologous recombination of an internal recA fragment contained on the mobilizable suicide vector. The recA mutant strain was more sensitive to UV radiation and showed a reduced recombinatorial proficiency than the isogenic parent strain. These data suggest that recA of A. actinomycetemcomitans SUNY 465 is involved in the repair of DNA damage caused by UV irradiation and homologous recombination as determined for other bacteria. PMID- 11786263 TI - Aminoguanidine renders inducible nitric oxide synthase knockout mice more susceptible to Salmonella typhimurium infection. AB - Aminoguanidine (AG), a nitric oxide synthase (NOS) inhibitor, has been widely used to study the role of inducible NOS (iNOS) in host defense against infections caused by various pathogens including Salmonella typhimurium. iNOS has been reported to play an important role in host defense against S. typhimurium infection both in vitro and in vivo. In this report we show those AG treatment lead to weight loss in both wild-type and iNOS knockout mice, and rendered them more susceptible to Salmonella infection. These results suggest that AG may have side effects other than the inhibition of iNOS, and that data obtained from studies using AG should be interpreted with caution. PMID- 11786264 TI - Detection of early phase specific surface appendages during germination of Aspergillus fumigatus conidia. AB - During the past 15 years the saprophytic fungus Aspergillus fumigatus has become the most prevalent airborne fungal pathogen, causing severe and often fatal infections especially in immuno-compromised patients. Germination of inhaled conidia is an early and crucial event in the infection process of A. fumigatus. In this study we have analyzed morphological changes that take place during this differentiation process using scanning electron microscopy. Our data show that (i) the hydrophobic surface layer of resting conidia seems to be shed before the cells start to swell and (ii) that filamentous surface appendages are expressed at a very early phase of the germtube formation. These surface structures were only found on the first few microm of the germtube, but were absent from the surface of mycelial hyphae and resting or swollen conidia. The highly regulated expression of these novel surface organelles suggests that they may play an important role during early germination and represent a potential target for future anti-A. fumigatus therapies. PMID- 11786265 TI - Identification of enteric pathogens by heat shock protein 60 kDa (HSP60) gene sequences. AB - A highly specific and reproducible approach for the simultaneous detection of enteric pathogenic bacteria was developed using bacterial hsp60 gene and molecular biological tools. A single pair of universal primers was derived from the highly conserved sequence of hsp60 genes encompassing a 600-bp hypervariable region. PCR amplification followed by either dot blot hybridization or restriction enzyme digestion performed on 38 enteric bacteria indicated that this approach could differentiate not only different genera such as Campylobacter, Yersinia and Vibrio, but also species that are closely related genetically, such as between C. jejuni and C. coli, or between Salmonella and Shigella or Escherichia coli. PMID- 11786266 TI - Genetic identification of two functional regions in the antitoxin of the parD killer system of plasmid R1. AB - We report the identification and genetic analysis of mutants in the antitoxin of the parD (kis, kid) killer system of plasmid R1. Missense mutants placed at codons 10, 11, 12 and 18 maintained the antitoxin activity of Kis, but not the ability of this protein to co-regulate the parD system together with the Kid toxin. Deletion of the last 33 amino acids of Kis inactivated the antitoxin activity of the protein and reduced substantially, but not completely, its regulatory activity. These results define two functional regions in Kis: an amino terminal region which is specifically involved in regulation, and a carboxy terminal region of the protein, which is important both for its regulatory and antitoxin activities. PMID- 11786267 TI - Heme-regulated expression of two yeast acyl-CoA:sterol acyltransferases is involved in the specific response of sterol esterification to anaerobiosis. AB - Sterol esterification in Saccharomyces cerevisiae is catalyzed by two acyl CoA:sterol acyltransferases encoded by the genes ARE1 and ARE2. Using double mutants in the HEM1 gene and individual ARE genes we demonstrated that the relative contribution of these two enzymes to sterol esterification was dependent on cellular heme status. Observed changes in sterol esterification could be explained by a different effect of heme on the transcription of both genes: while the ARE1 transcript level was elevated in heme-deficient and anaerobic cells, the ARE2 gene transcript was more abundant in aerobic cells competent for heme synthesis. Our results indicate that transcriptional regulation of ARE genes by heme and specific substrate preferences of Are1p and Are2p may be involved in the adaptation of yeast sterol metabolism to hypoxia. PMID- 11786270 TI - Improved xenograft targeting of tumor-specific anti-epidermal growth factor receptor variant III antibody labeled using N-succinimidyl 4-guanidinomethyl-3 iodobenzoate. AB - Monoclonal antibodies (mAbs) such as the tumor-specific anti-epidermal growth factor receptor variant III (EGFRvIII) that are internalized and degraded after cell binding necessitate the use of radioiodination methods that minimize the loss of radioactivity from the tumor cell after intracellular processing. The purpose of the current study was to determine the suitability of N-succinimidyl 4 guanidinomethyl-3-iodobenzoate (SGMIB) for labeling this internalizing mAb. A series of paired-label biodistribution experiments were performed in athymic mice bearing subcutaneous, EGFRvIII-expressing, D-256 human glioma and U87 Delta EGFR xenografts. The tissue distribution of radioiodine activity following injection of anti-EGFRvIII mAb L8A4 labeled using N-succinimidyl 4-guanidinomethyl-3 iodobenzoate (SGMIB) were compared to those for mAb labeled using Iodogen, N succinimidyl 3-iodo-5-pyridinecarboxylate (SIPC) as well as the Boc-protected precursor of SGMIB. Tumor uptake of radioiodine activity for mAb labeled via SGMIB was significantly higher than co-administered L8A4 radioiodinated by other methods. For example, 3 days after injection, D-256 tumor uptake of L8A4 labeled via SGMIB was 20.4 +/- 4.6% ID/g compared with 11.7 +/- 5.5% ID/g when the SIPC method was used. Thyroid uptake for L8A4 (SGMIB) was up to 36 times lower than L8A4 (Iodogen) and less than 0.35% in all experiments, indicating a low degree of deiodination in vivo. These results suggest that SGMIB may be a useful reagent for the radioiodination of this internalizing anti-EGFRvIII mAb. PMID- 11786271 TI - Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS). AB - The sodium-iodide symporter (NIS), which transports iodine into the cell, is expressed in thyroid tissue and was recently found to be expressed in approximately 80% of human breast cancers but not in healthy breast tissue. These findings raised the possibility that therapeutics targeting uptake by NIS may be used for breast cancer treatment. To increase the efficacy of such therapy it would be ideal to identify a radioactive therapy with enhanced local emission. The feasibility of using the powerful beta-emitting radiometal (188)Re in the form of (188)Re-perrhenate was therefore compared with 131I for treatment of NIS expressing mammary tumors. In the current studies, using a xenografted breast cancer model induced by the ErbB2 oncogene in nude mice, (188)Re-perrhenate exhibited NIS-dependent uptake into the mammary tumor. Dosimetry calculations in the mammary tumor demonstrate that (188)Re-perrhenate is able to deliver a dose 4.5 times higher than (131)I suggesting it may provide enhanced therapeutic efficacy. PMID- 11786272 TI - PET imaging of dopamine transporters in the human brain using [(11)C]-beta-CPPIT, a cocaine derivative lacking the 2 beta-ester function. AB - The compound 3 beta-(4'-chlorophenyl)-2 beta-(3'-phenylisoxazol-5'-yl)tropane (CPPIT or RTI 177) is a 2beta-heterocyclic substituted cocaine congener with high in vitro selectivity and affinity for the dopamine transporter relative to serotonin and norepinephrine transporters. The aim of the present study was to evaluate the in vivo selectivity of [(11)C]-beta-CPPIT and to determine whether [(11)C]-beta-CPPIT may be a suitable alternative to existing DAT PET radioligands. [(11)C]-beta-CPPIT was prepared by N-alkylation of the free amine with [(11)C]methyl iodide. In mouse brain, the striatal binding of [(11)C]-beta CPPIT was reduced significantly by preinjecting the dopamine reuptake antagonist GBR 12909 (5 mg/kg). By contrast, radioactivity uptake in the brain was not affected significantly by the preinjection of citalopram (5 mg/kg) and desipramine (5 mg/kg), inhibitors for the serotonin and norepinephrine transporters, respectively. No effect was also observed by pretreatment with ketanserin (2.5 mg/kg) a compound with high affinity for the 5-HT(2A)-receptor and the vesicular monoamine transporter. In a PET study with six healthy volunteers high striatal uptake was observed. The distribution pattern of [(11)C] beta-CPPIT was similar to the known distribution of the dopamine transporter in the human brain. Compared to (123)I labeled beta-CIT, the rate of metabolic degradation of [(11)C]-beta-CPPIT was almost twofold slower suggesting that bioisosteric heterocyclic substitution of the ester group at the 2 beta-position of the tropane ring does have an influence on the rate of metabolism of [(11)C] beta-CPPIT. The rank order of the distribution volumes obtained via the one tissue compartment model is also similar to the reported distribution of DAT. These preliminary results suggest that [(11)C]-beta-CPPIT may be a useful PET radioligand for the visualization and quantification of dopamine transporters in man. PMID- 11786273 TI - Mapping adenosine A(1) receptors in the cat brain by positron emission tomography with [(11)C]MPDX. AB - We evaluated the potential of [(11)C]MPDX as a radioligand for mapping adenosine A(1) receptors in comparison with previously proposed [(11)C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [(11)C]MPDX (Ki = 4.2 nM) was much higher and washed out faster than that of [(11)C]KF15372 (Ki = 3.0 nM), and was blocked by carrier-loading or displaced with an A(1) antagonist. The regional A(1) receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [(11)C]MPDX PET has a potential for mapping adenosine A(1) receptors in brain. PMID- 11786274 TI - PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor. AB - NAD-299 is a selective 5-HT(1A) receptor antagonist that is currently developed as a putative antidepressant drug. [(11)C]NAD-299 was examined in the cynomolgus monkey brain with positron emission tomography (PET). After radioligand injection high accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, regions known to contain a high density of 5-HT(1A) receptors. Peak equilibrium appeared already at about 10 min after i.v. injection. Pre-treatment with a high dose of the antagonist WAY-100635 reduced the amount of radioactivity in the cortex and the raphe to the level of the cerebellum. A strong pre-treatment effect could also be achieved using pindolol, a partial agonist at the 5-HT(1A)-receptors. The appearance of labeled metabolites in monkey plasma was measured with HPLC. At 45 minutes after injection 49% (range 27-55%, n = 5) of radioactivity in monkey plasma represented unchanged radioligand. [(11)C]NAD-299 was metabolized to more polar labeled metabolites of which one has the same chromatographic mobility as the descyclobutyl analogue of NAD-299 (NAD-272). The results indicate that [(11)C]NAD 299 has potential as a PET radioligand for studies of 5-HT(1A) receptors in the primate brain. PMID- 11786275 TI - [(11)C]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers. AB - The R and S enantiomers of [(11)C]GR89696, [(11)C]-methyl 4-[(3,4 dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate, were synthesized from their appropriate chiral precursors and [(11)C]methyl chloroformate. The [(11)C]-labeled R enantiomer of GR89696, also known as GR103545, demonstrated high affinity in mouse brain with region to cerebellar ratios at 90 minutes of 11.4 and 8.7 for the hypothalamus and olfactory tubercle, respectively. The [(11)C]-labeled S enantiomer showed low affinity and region to cerebellar ratios of 1 for all brain regions. The [(11)C]-labeled GR103545 exhibited a selective and saturable binding for the kappa opioid receptor. PMID- 11786276 TI - Radiochemical synthesis and biodistribution of a novel maxi-K potassium channel opener. AB - The racemate 1, ((+/-)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6 (trifluoromethyl)- 2H-indol-2-one), is a potent, specific and novel opener of cloned large-conductance, calcium-activated (maxi-K) potassium channels. One of its enantiomers, BMS-204352 (MaxiPost), is undergoing clinical evaluation for efficacy in patients with suspected acute stroke. In the current study, we have prepared [(18)F]-labeled 1 using a silver assisted nucleophilic substitution to examine its distribution and disposition in the rat, with particular emphasis on the brain. Biodistribution studies in rats confirm that brain uptake is rapid and occurs at high levels, and indicate that a major fraction of the compound in the brain does not accumulate by a specific, saturable mechanism. PMID- 11786277 TI - Biodistribution and catabolism of (18)F-labeled neurotensin(8-13) analogs. AB - 4-([(18)F]fluoro)benzoyl-neurotensin(8-13) ((18)FB-Arg(8)-Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 1) and two analogs stabilized in one and two positions ((18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 2, (18)FB Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)-Tle(12)-Leu(13)-OH, 3) were synthesized in a radiochemical yield of 25-36% and a specific activity of 5-15 GBq/mmol. The peptides were evaluated in vitro and in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells in vitro, and the fluorinated peptides were able to mobilize intracellular Ca(2+) of WiDr cells. In in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumed to be due to degradation in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET. PMID- 11786278 TI - In vivo imaging of insulin receptors by PET: preclinical evaluation of iodine-125 and iodine-124 labelled human insulin. AB - [A(14)-*I]iodoinsulin was prepared for studies to assess the suitability of labeled iodoinsulin for positron emission tomography (PET). Iodine-125 was used to establish the methods and for preliminary studies in rats. Further studies and PET scanning in rats were carried out using iodine-124. Tissue and plasma radioactivity was measured as the uptake index (UI = [cpm x (g tissue)(-1)]/[cpm injected x (g body weight)(-1)]) at 1 to 40 min after intravenous injection of either [A(14)-(125)I]iodoinsulin or [A(14)-(124)I]iodoinsulin. For both radiotracers, initial clearance of radioactivity from plasma was rapid (T(1/2) approximately 1 min), reaching a plateau (UI = 2.8) at approximately 5 min which was maintained for 35 min. Tissue biodistributions of the two radiotracers were comparable; at 10 min after injection, UI for myocardium was 2.4, liver, 4.0, pancreas, 5.4, brain, 0.17, kidney, 22, lung, 2.3, muscle, 0.54 and fat, 0.28. Predosing rats with unlabelled insulin reduced the UI for myocardium (0.95), liver (1.8), pancreas (1.2) and brain (0.08), increased that for kidney (61) but had no effect on that for lung (2.5), muscle (0.50) or fat (0.34). Analysis of radioactivity in plasma demonstrated a decrease of [(125)I]iodoinsulin associated with the appearance of labeled metabolites; the percentage of plasma radioactivity due to [(125)I]iodoinsulin was 40% at 5 min and 10% at 10 min. The heart, liver and kidneys were visualized using [(124)I]iodoinsulin with PET. PMID- 11786279 TI - Synthesis and characterization of (99m)Tc- and (188)Re-complexes with a diamido dihydroxymethylenephosphine-based bifunctional chelating agent (N(2)P(2)-BFCA). AB - A diamido-dihydroxymethylenephosphine (N(2)P(2)) bifunction chelating agent (BFCA) was shown to form well-defined (99m)Tc- and (188)Re-chelate structures. The 4, 4-bis [bis-hydroxymethyl-phosphonyl-propylcarbonmoyl]-butyric acid bifunctional chelating agent (N(2)P(2)-BFCA) formed stable complexes with (99m)Tc and (188)Re in >95% yield with high radiochemical purity (RCP). The biodistribution of the (99m)Tc- and (188)Re-N(2)P(2)-BFCAs after intravenous injection studied in normal mice showed the activity was excreted primarily via renal-urinary pathway indicating their use for labeling peptides with (99m)Tc and (188)Re. PMID- 11786280 TI - Novel chelating agents for potential clinical applications of copper. AB - Copper offers a unique selection of radioisotopes ((60)Cu, (61)Cu, (62)Cu, (64)Cu, and (67)Cu) with half-lives ranging from 9.8 min to 61.9 h suitable for imaging and/or radiotherapy. In peptide/antibody targeted radiotherapy one of the most studied chelating agents for copper, 1,4,8,11-tetraazacyclotetradecane 1,4,8,11-tetraacetic acid (TETA), has been employed in clinical trials, but transchelation to ceruloplasmin and/or superoxide dismutase in vivo has been noted. In this study, a series of novel hexadentate chelating agents based on N,N',N"-tris(2-pyridylmethyl)-1,3,5-cis,cis,-triaminocyclohexane (tachpyr) have been synthesized and the serum stability of their copper complexes was evaluated as compared to TETA. Copper complexes of tachpyr modified at the 3, 4, or 5 position or with replacement of pyridine by imidazole have serum stability comparable to Cu[TETA]. When the complexes were cross-challenged, Cu[TETA] versus tachpyr or 1,3,5-cis,cis,-triaminocyclohexane- N,N',N"-tris-(2-methyl-(N methylimidazole)) (IM), tachpyr and IM appear to have superior copper chelation ability to TETA. When challenged by a large excess of non-radioactive copper, copper exchange with the tachpyr radio-copper complex was observed. However, tachpyr clearly exhibited a significant preference for Cu(II) over Zn(II) or Fe(III). Therefore, tachpyr, 1,3,5-cis,cis,-triaminocyclohexane-N,N',N"-tri-(3 methyl-2-methylpyridineimine) (tachpyr(3-Me)), 1,3,5-cis,cis,-triaminocyclohexane N,N',N"-tri-(4-methyl-2-methylpyridineimine) (tachpyr(4-Me)), 1,3,5-cis,cis, triaminocyclohexane-N,N',N"-tri-(5-methyl-2-methylpyridineimine) (tachpyr(5-Me)) and IM easily form copper complexes with high stability. These novel chelating agents provide an attractive lead for creation of new copper radiopharmaceuticals for diagnosis and therapy applications. PMID- 11786281 TI - Nitriles form mixed-coligand complexes with (99m)Tc-HYNIC-peptide. AB - Using a 12-amino acid peptide conjugated with HYNIC as a model, we investigated nitriles as possible coligands for labeling with (99m)Tc. After the preparation of the (99m)Tc labeled HYNIC-peptide using tricine as coligand, the addition of acetonitile was found by reverse phase HPLC to block further coligand exchange with ethylenediamine diacetic acid (EDDA) at room temperature. The addition of this nitrile changed the pharmacokinetics of the (99m)Tc labeled peptide in normal mice towards faster clearance and significant differences in accumulation in most tissues sampled. By replacing acetonitrile with cyanoacetate, a nitrile not present in the HPLC eluant, it was possible to show the existence of a new, more hydrophilic, species by reverse phase HPLC. We conclude that nitriles can act as coligands for HYNIC-conjugated peptides labeled with (99m)Tc and tricine. Furthermore, the presence of acetonitrile during Sep-Pak or HPLC purification may inadvertently generate a mixed tricine/acetonitile coligand (99m)Tc-HYNIC-peptide complex. PMID- 11786282 TI - Estimate the time varying brain receptor occupancy in PET imaging experiments using non-linear fixed and mixed effect modeling approach. AB - Positron-Emission Tomography (PET) is an imaging technology currently used in drug development as a non-invasive measure of drug distribution and interaction with biochemical target system. The level of receptor occupancy achieved by a compound can be estimated by comparing time-activity measurements in an experiment done using tracer alone with the activity measured when the tracer is given following administration of unlabelled compound. The effective use of this surrogate marker as an enabling tool for drug development requires the definition of a model linking the brain receptor occupancy with the fluctuation of plasma concentrations. However, the predictive performance of such a model is strongly related to the precision on the estimate of receptor occupancy evaluated in PET scans collected at different times following drug treatment. Several methods have been proposed for the analysis and the quantification of the ligand-receptor interactions investigated from PET data. The aim of the present study is to evaluate alternative parameter estimation strategies based on the use of non linear mixed effect models allowing to account for intra and inter-subject variability on the time-activity and for covariates potentially explaining this variability. A comparison of the different modeling approaches is presented using real data. The results of this comparison indicates that the mixed effect approach with a primary model partitioning the variance in term of Inter Individual Variability (IIV) and Inter-Occasion Variability (IOV) and a second stage model relating the changes on binding potential to the dose of unlabelled drug is definitely the preferred approach. PMID- 11786283 TI - Quantification of Kryptofix 2.2.2 in 2-[(18)F]FDG and other radiopharmaceuticals by LC/MS/MS. AB - A high-performance liquid chromatography-tandem mass spectrometric method (LC/MS/MS) was developed and validated for the quantitative analysis of Kryptofix (K-222) in the radiopharmaceuticals of 2-deoxy-2-[(18)F] fluoro-D-glucose (2 [(18)F]FDG) and 3-(3-((3-fluoropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6 tetrahydro-1-methylpyridine (FPTZTP). With an internal standard, the limit of quantitation for K-222 was 1.0 ng/ml. This is so far the most sensitive method for the quantification of K-222. Excellent linearity (RSQ = 0.9997) was obtained over the range of 1.0-100 ng/ml. Good precision and accuracy were also observed. The method is amenable to the validation of radiosynthetic methods. PMID- 11786284 TI - Re: A. Amman, et al., Surfactant protein B labelled with [(99m)Tc(CO)(3)(H(2)O)(3)](+) retains biological activity in vitro. Nuc. Med. Biol. 28 (2001) 243-250. PMID- 11786286 TI - Pregnant women deserve informed consent too. PMID- 11786287 TI - Provider evaluation of a multifaceted system of care to improve recognition and management of pregnant women experiencing domestic violence. AB - This article describes the provider evaluation of a multifaceted system of care for pregnant women experiencing domestic violence and who receive prenatal care in an urban family practice site, one of four national demonstration projects. Providers reported changes in their own self-efficacy and behavior, but showed little improvement in overall attitudes or knowledge. Focus groups revealed that an easily accessible domestic violence coordinator was important, whereas providers stated that most domestic violence protocol materials were not useful. Guidelines that rely on training and protocols have had limited national success, suggesting that additional systems of care such as written chart prompts, quality improvement, and on-site domestic violence services may be necessary. This intervention was well received by providers, a key factor in any effort to alter provider behavior. PMID- 11786288 TI - Depression and negative life events among pregnant African-American and Hispanic women. AB - Depression, social support, and life events were assessed in a sample of African American and Hispanic women (N = 148) with uncomplicated pregnancies. Over half (51%) showed elevated depressive symptoms. Overall, women had fewer social supports and more negative life events than found in previous studies. African Americans had more practical social support and persons in their support networks than Hispanics. Over a third of the sample (37%) had lost an important person in the past year. Depressed women reported more negative events than nondepressed women. Many negative life events and few social supports place minority women at risk for prenatal depression. PMID- 11786289 TI - Drug testing welfare recipients--false positives, false negatives, unanticipated opportunities. AB - Substance abuse and dependence are among the most common psychiatric disorders among pregnant and parenting women. These disorders among welfare recipients have attracted special concern. Chemical testing has been proposed to identify illicit drug use in this population. This analysis scrutinizes the potential value of drug testing, using recent data from the Women's Employment Study and the National Household Survey of Drug Abuse. One-fifth of recipients reported illicit substance use during the previous year. However, less than 5% satisfied diagnostic screening criteria for illicit drug dependence. Most recipients with psychiatric disorders or alcohol dependence reported no recent illicit drug use, and, thus, would not be detected through chemical tests. Although illicit drug users are rarely dependent, many face barriers to self-sufficiency. Screening and assessment programs should distinguish use from dependence, and should also identify alcohol dependence and psychiatric disorders. States should provide a range of treatment services to address these concerns. PMID- 11786290 TI - Screening and treatment of anxiety disorders in pregnant and lactating women. AB - Untreated anxiety disorders during pregnancy and the postpartum period may pose significant risks to the unborn fetus and interfere with a mother's ability to properly care for her newborn child. As the symptoms of anxiety disorders are often similar to those found in pregnancy, careful screening for anxiety disorders in pregnant women is essential. For women suffering from anxiety disorders during or after pregnancy, safe and effective treatment is needed. In this article, suggestions are offered for thorough assessment of anxiety disorders in pregnant and breastfeeding women. Treatment options are discussed with an emphasis on pharmacologic and cognitive-behavioral treatment. PMID- 11786291 TI - Long-term health consequences of delayed childbirth: NHANES III. AB - Medicine has pointed to short-term, immediate health risks to child and mother of delaying childbearing past the age of 35 years. The long-term health consequences of delayed childbearing have not been the subject of research. Are women who delay having children to pursue education and career goals placing their later health status at risk? To address this question, the study utilizes data from the National Health and Nutrition Examination Survey III 1988-1994. The analyses used odds ratios obtained from stepwise logistic regression analysis to assess women's health risks. The results are suggestive of selective risk enhancement from delayed childbirth with regard to cardiovascular disease and risk factors, especially diabetes and hypertension, and congestive heart failure. Risks were further enhanced in terms of dental health, blood abnormalities, physical mobility, and vision difficulties. Whereas delaying childbearing may indicate a readiness on the part of women and men to delay becoming parents, the present study suggests that not all is currently known about the long-term health consequences of such decisions to delay childbearing. PMID- 11786292 TI - Performance indicators in women's health: incorporating women's health in the health plan employer data and information set (HEDIS). AB - The Health plan Employer Data and Information Set (HEDIS) is limited in its scope of women's health-related performance measures. Realizing this, the National Committee for Quality Assurance developed the Women's Health Measurement Advisory Panel (MAP) to expand and develop HEDIS measures to better represent women's health issues. This paper outlines the development of several new women's health related performance measures and highlights the complexities of creating new measures to assess the quality of care provided to women through our nation's managed care organizations. PMID- 11786293 TI - Regulation of vesicle trafficking, transcription, and meiosis: lessons learned from yeast regarding the disparate biologies of phosphatidylcholine. AB - Phosphatidylcholine (PtdCho) is the major phospholipid present in eukaryotic cell membranes generally comprising 50% of the phospholipid mass of most cells and their requisite organelles. PtdCho has a major structural role in maintaining cell and organelle integrity, and thus its synthesis must be tightly monitored to ensure appropriate PtdCho levels are present to allow for its coordination with cell growth regulatory mechanisms. One would also expect that there needs to be coordinated regulation of PtdCho synthesis with its transport from its site of synthesis to cellular organelles to ensure organellar structures and functions are maintained. Each of these processes need to be intimately coordinated with cellular growth decision making processes. To this end, it has recently been revealed that ongoing PtdCho synthesis is required for global transcriptional regulation of phospholipid synthesis. PtdCho is also a major component of intracellular transport vesicles and the synthesis of PtdCho is intimately involved in the regulation of vesicle transport from the Golgi apparatus to the cell surface and the vacuole (yeast equivalent of the mammalian lysosome). This review details some of the more recent advances in our knowledge concerning the role of PtdCho in the regulation of global lipid homeostasis through (i) its restriction of the trafficking of intracellular vesicles that distribute lipids and proteins from their sites of synthesis to their ultimate cellular destinations, (ii) its regulation of specific transcriptional processes that coordinate lipid biosynthetic pathways, and (iii) the role of PtdCho catabolism in the regulation of meiosis. Combined, these regulatory roles for PtdCho ensure vesicular, organellar, and cellular membrane biogenesis occur in a coordinated manner. PMID- 11786294 TI - Does bilirubin play a role in the pathogenesis of both cholesterol and pigment gallstone formation? Direct and indirect influences of bilirubin on bile lithogenicity. AB - Bilirubin is found in the center of cholesterol gallstones, but its pathogenic role in their formation is unknown. Bilirubin causes a disproportionate reduction of biliary lipid secretion without affecting bile salt secretion in association with a change of biliary lecithin species, which modulates the cholesterol crystallization process. Therefore, the present study investigated whether bilirubin can influence the cholesterol crystallization procedure, and the mechanism(s) of any such action. Supersaturated model bile was prepared (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 9.0 g/dl, and cholesterol saturation index of 1.8), and cholesterol crystallization was monitored over time using a spectrophotometer and video enhanced differential contrast microscopy in the absence or presence of bilirubin (at a final concentration of 10 microM, 20 microM, 40 microM, and 100 microM). Bilirubin enhanced the onset of cholesterol crystallization by 50%, whereas the crystal growth rate and final crystal mass were reduced at a high concentration of bilirubin. Taken together, these results suggest that bilirubin influences the cholesterol crystallization process, by either a direct interaction with biliary lipids that alters metastability, an indirect alteration of the bile salt micellar lipid holding capacity, or both. Thus, bilirubin may play a role in the pathogenesis of both cholesterol and pigment gallstones. PMID- 11786295 TI - The CTP:phosphocholine cytidylyltransferase encoded by the licC gene of Streptococcus pneumoniae: cloning, expression, purification, and characterization. AB - Streptococcus pneumoniae is a member of a small group of bacteria that display phosphocholine on the cell surface, covalently attached to the sugar groups of teichoic acid and lipoteichoic acid. The putative pathway for this phosphocholine decoration is, in its first two enzymes, functionally similar to the CDP-choline pathway used for phosphatidylcholine biosynthesis in eukaryotes. We show that the licC gene encodes a functional CTP:phosphocholine cytidylyltransferase (CCT). The enzyme has been expressed and purified to homogeneity. Assay conditions were optimized, particularly with respect to linearity with time, pH, Mg(2+), and ammonium sulfate concentration. The pure enzyme has K(M) values of 890+/-240 microM for CTP, and 390+/-170 microM for phosphocholine. The k(cat) is 17.5+/-4.0 s(-1). S. pneumoniae CTP:phosphocholine cytidylyltransferase (SpCCT) is specific for CTP or dCTP as the nucleotide substrate. SpCCT is strongly inhibited by Ca(2+). The IC(50) values for recombinant and native SpCCT are 0.32+/-0.04 and 0.27+/-0.03 mM respectively. The enzyme is also inhibited by all other tested divalent cations, including Mg(2+) at high concentrations. The cloning and expression of this enzyme sets the stage for design of inhibitors as possible antipneumococcal drugs. PMID- 11786297 TI - Phosphatidic acid is the prominent product of endogenous neuronal nuclear lipid phosphorylation, an activity enhanced by sphingosine, linked to phospholipase C and associated with the nuclear envelope. AB - Using endogenous lipid substrates, assays of lipid phosphorylation indicated that neuronal nuclei had a considerable superiority in phosphatidic acid (PA) formation when compared with homogenates and other subfractions of cerebral cortex. This predominance of neuronal nuclear PA labelling was linked to a sizable pool of nuclear diacylglycerols that expanded significantly with incubation. PA was also the dominant product of neuronal nuclear lipid phosphorylation reactions. Nuclear envelope preparations and the parent neuronal nuclei showed specific rates of PA formation that were comparable, based upon membrane phospholipid contents. As well, using an exogenous diacylglycerol substrate, the distribution of diacylglycerol kinase activities closely followed phospholipid contents of subfractions derived from the neuronal nucleus during envelope preparation. This evidence suggested an association between diacylglycerol kinase and the neuronal nuclear envelope. Nuclear PA formation increased in the presence of sphingosine, while sphingosine decreased PA formation in other subfractions. Likely sphingosine exerted its effect on nuclear diacylglycerol kinase, as sphingosine did not elevate levels of nuclear diacylglycerols. Phosphoinositidase C was present in the nuclei and inhibitors of this enzyme did decrease PA formation, indicating diacylglycerols from inositides as substrates for nuclear diacylglycerol kinase. The nuclear envelope fraction had a considerably lower specific phosphoinositidase C activity than the parent nuclei, and showed an activation of PA formation by sphingosine, but a less efficient handling of the exogenous diacylglycerol substrate. It is possible that phosphoinositidase C and diacylglycerol kinase are closely situated within the neuronal nuclei, and a loss of the former activity may compromise the latter. PMID- 11786296 TI - The influence of chylomicron remnants on cholesteryl ester metabolism in cultured rat hepatocytes: comparison of the effects of particles enriched in n-3 or n-6 polyunsaturated fatty acids. AB - The effect of chylomicron remnants derived from fish oil (rich in n-3 polyunsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids) on the formation and hydrolysis of cholesteryl esters in cultured rat hepatocytes was investigated. Hepatocytes were incubated with or without fish or corn oil chylomicron remnants (0.25-0.75 mM triacylglycerol), and the activity of acyl-CoA:cholesterol acyltranferase (ACAT) and cholesteryl ester hydrolases in the cytosol (cCEH) and endoplasmic reticulum (erCEH), and the expression of mRNA for ACAT1, ACAT2 and cCEH, and of enzyme protein for erCEH was determined. Addition of either type of remnants to hepatocyte cultures resulted in a decreased activity of erCEH, cCEH (after 6 and 19 h incubation), and of ACAT (after 6 h only). Hepatocyte levels of mRNA encoding ACAT1 and ACAT2 were not affected by either type of chylomicron remnants after 6 h of incubation, while ACAT2 mRNA levels were down-regulated by fish oil remnants as compared with corn oil remnants, and also with control cells in the long term (19 h). In contrast, cCEH mRNA levels were down-regulated by chylomicron remnants derived from corn oil but not fish oil. The expression of erCEH protein was induced in response to the inhibitory effect of both types of remnants on the activity of the enzyme, with corn oil remnants having a significantly greater effect. These findings demonstrate that dietary polyunsaturated fatty acids when delivered to hepatocytes in chylomicron remnants regulate the activity of the enzymes governing the intracellular cholesteryl ester balance, and suggest that dietary n 3 and n-6 polyunsaturated fatty acids or a metabolite thereof have differential effects on the expression of their genes at the mRNA and post-transcriptional levels. PMID- 11786298 TI - Stably transfected ABCA1 antisense cell line has decreased ABCA1 mRNA and cAMP induced cholesterol efflux to apolipoprotein AI and HDL. AB - Using a sensitive real time fluorescent PCR assay, ABCA1 mRNA levels were induced by approximately 50-70-fold following 8Br-cAMP treatment of the RAW264 murine macrophage cell line, concomitant with the induction of cholesterol efflux to apoAI and HDL. A stably transfected ABCA1 antisense cDNA cell line was created, which led to approximately 50-70% reductions in ABCA1 mRNA levels in basal and 8Br-cAMP-treated cells, and diminished to the same extent the 8Br-cAMP-mediated efflux of cholesterol to apolipoprotein AI and HDL. These data demonstrate that ABCA1 is necessary for the cAMP-induced lipid efflux to both apoAI and HDL. PMID- 11786299 TI - On the anti-atherogenic effect of the antioxidant BHT in cholesterol-fed rabbits: inverse relation between serum triglycerides and atheromatous lesions. AB - We have shown that inclusion of the antioxidant butylated hydroxytoluene (BHT) in the diet protects against development of atherosclerotic lesions in cholesterol fed rabbits. In parallel, BHT treatment results in increased plasma triglyceride levels. The present study explores the relationship between the triglyceride inducing and protective effects of BHT in two different studies. The combined material contains 22 rabbits fed cholesterol and 18 rabbits fed cholesterol in combination with 1% BHT. In the BHT group there was an inverse relationship between triglyceride exposure/cholesterol exposure and extent of lesions with r=0.74 (P=0.0005). Our results show that increased triglyceride exposure parallels the anti-atherogenic effect of BHT. There was no significant correlation between atheromatosis and serum BHT levels. beta-very low density lipoprotein (beta-VLDL) from cholesterol and BHT animals was triglyceride enriched and smaller compared to beta-VLDL from cholesterol-fed animals, but there was no significant association between the anti-atherogenic effect of BHT and particle size or apolipoprotein pattern of LDL or beta-VLDL. LDL isolated from rabbits treated with cholesterol and BHT was less sensitive to oxidative modification than LDL isolated from rabbits treated with cholesterol only. In conclusion, our results demonstrate that the degree of triglyceride exposure may be an important modulator of the anti-atherogenic effect of an antioxidant. PMID- 11786300 TI - Cholesterol enrichment upregulates intercellular adhesion molecule-1 in human vascular endothelial cells. AB - Hypercholesterolemia is a major risk factor for atherosclerosis, but the mechanism by which cholesterol activates the endothelium remains undocumented. The present investigation was undertaken to investigate the role of cholesterol, one of the bioactive moieties of the low-density lipoprotein (LDL) particle, in initiating of intracellular signaling in endothelial cells (ECs) and culminating in increased abundance of the intercellular adhesion molecule-1 (ICAM-1). Cholesterol was delivered to human umbilical vein ECs (HUVECs) via cholesterol enriched liposomes. In HUVECs, the cellular cholesterol:phospholipid ratio increased after 1 h of exposure to cholesterol. The level of ICAM-1 increased in both mRNA and protein after 24 h of cholesterol exposure. ICAM-1 mRNA half-life was not affected by cholesterol exposure. Promoter studies showed greater than two-fold activation of the ICAM-1 gene expression after cholesterol exposure. Electrophoretic mobility shift assay showed that activator protein-1 (AP-1) activity substantially increased after 2 h of exposure to cholesterol. In contrast, cholesterol did not affect nuclear factor-kappaB (NF-kappaB) activity. Results of trans-reporting assay revealed 2.5-fold increased expression of the AP 1-dependent reporter gene after cholesterol exposure whereas NF-kappaB-dependent expression was not affected. The AP-1/Ets (-891 to -908) site, one of the three AP-1-like sites in the ICAM-1 promoter, was most responsive to cholesterol. These data demonstrate for the first time that cholesterol enrichment phenotypically modulates ECs by transcriptionally upregulating ICAM-1 expression. PMID- 11786304 TI - Serotonergic targets in depression. AB - Serotonin reuptake inhibitors have proved to be a very effective treatment for depression and have strengthened the hypothesis that impaired 5-hydroxytryptamine (5-HT) neurotransmission may contribute to the underlying cause of depressive disorders. Extensive research has been carried out to investigate other 5-HT targets associated with the disease and studies involving combination treatments with selective serotonin reuptake inhibitors and 5-HT(1A) receptor ligands are currently being carried out in the clinic. Whether other 5-HT receptor subtypes are involved in the aetiology of depression remains to be seen. PMID- 11786305 TI - Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. AB - Corticotropin-releasing factor (CRF) and its related family members are implicated in stress-related disorders such as anxiety and depression. Recently, two new members of this neuropeptide family have been discovered in the brain: urocortin II (also known as stresscopin-related peptide) and urocortin III (also known as stresscopin). These urocortins are selective agonists for the CRF(2) receptor, show a distinct neuroanatomical localization and are involved in stress coping responses such as anxiolysis. Thus, CRF, the urocortins and their receptors form an intricate network in the brain involved in the acute phase as well as the recovery phase of the stress response. PMID- 11786306 TI - Stem cells in brain plasticity and repair. AB - Findings over the past decade demonstrating persistent neurogenesis in the adult brain have overturned dogma, provoked reevaluation of cellular plasticity in the mature brain and raised hopes for novel approaches to brain repair. Recent discoveries reveal that neurogenesis is regulated by environmental stimuli and can be responsive to brain injury. This cellular plasticity may indicate a possible endogenous repair program. By understanding the mechanisms involved, it may be possible to harness this plasticity to recruit endogenous neural stem cells or to graft stem cells to achieve structural brain repair. PMID- 11786307 TI - Allosteric modulators of group I metabotropic glutamate receptors: novel subtype selective ligands and therapeutic perspectives. AB - Recent drug discovery programs aimed at identifying selective metabotropic mGlu receptor ligands by high-throughput functional screening efforts have revealed subtype-selective allosteric modulators of mGlu1 and mGlu5 receptors that are structurally unrelated to glutamate. In contrast to competitive ligands, which bind to the glutamate binding site located in the large N-terminal extracellular domain, these modulators act as non-competitive antagonists, inverse agonists or positive modulators by binding to specific residues in the seven-transmembrane domain. More recent studies to assess the potential of these compounds in in vivo models of nervous system disorders have implicated the mGlu5 receptor subtype as a potentially important therapeutic target for inflammatory pain, anxiety, Parkinson's disease and drug abuse, and mGlu1 and mGlu5 receptors as potential targets for anticonvulsant and neuroprotective therapies. Very recent findings indicate an important regulatory role for intracellular proteins interacting with metabotropic glutamate receptors, which might constitute novel drug targets for modulating metabotropic glutamate receptor activity. PMID- 11786308 TI - Cannabinoids: a real prospect for pain relief? AB - Research on the therapeutic potential of cannabinoids has grown dramatically over the past few years. Recent advances include evidence that cannabinoid agonists are antihyperalgesic and antiallodynic in models of neuropathic pain. Development of novel cannabinoid agonists and cannabinoid preparations that are antinociceptive has important implications for the therapeutic use of this class of drugs. PMID- 11786310 TI - Chemokines in the brain: neuroimmunology and beyond. AB - Chemokines in the brain have been recognised as essential elements in neurodegenerative diseases and related neuroinflammation. Recent studies suggest that in addition to the orchestration of chemotaxis of immune cells, chemokines are also involved in neurodevelopment and neurophysiological signalling. PMID- 11786309 TI - The heterozygote reeler mouse as a model for the development of a new generation of antipsychotics. AB - Neurochemical and structural prefrontal cortex abnormalities, including decreased reelin and glutamic acid decarboxylase (GAD)(67) expression, decreased thickness, increased neuronal packing density and decreased neuropil and dendritic spine number, are characteristics of schizophrenia neuropathology. Reelin is an extracellular matrix protein secreted by GABAergic interneurons that, acting through pyramidal neuron integrin receptors, provides a signal for dendritic spine plasticity. Heterozygous reeler mice that exhibit a 50% downregulation of reelin expression (mRNA and protein) replicate the dendritic spine and GABAergic defects described in schizophrenia. This genetic mouse model may be of value to reveal those GABAergic and integrin receptor signal transduction mechanisms that are likely to be downregulated by reelin deficiency in the brain of schizophrenia patients. An understanding of the epigenetic regulation of reelin gene expression and of the possible pathogenetic role of reelin deficiency in schizophrenia, may become a major focus that will open new avenues for the treatment of this disease. PMID- 11786311 TI - Regulation of opioid receptor expression. AB - The cloning of the mu, delta and kappa opioid receptor genes in the early 1990s has allowed the genetic determinants that control the expression of each opioid receptor to be dissected. Regulation of these genes involves transcriptional and post-transcriptional events. At the transcriptional level, most recent studies have revealed both positive and negative roles for various transcription factors, vitamin A hormones and cytokines in opioid receptor gene regulation. Post transcriptional events involve alternative splicing and variation in mRNA stability and translation efficiency of these gene transcripts. Reports have also shown polymorphisms of the mu opioid receptor gene, primarily in the regulatory region, suggesting a potential connection between this gene and the likelihood of opioid abuse in humans. PMID- 11786312 TI - Oligomerization of opioid receptors: generation of novel signaling units. AB - G-protein-coupled receptors such as opioid receptors exist in oligomeric complexes. Homo-oligomerization of mu, delta, and kappa opioid receptors has been demonstrated, suggesting a critical functional role for receptor-receptor interactions. Hetero-oligomerization creates delta-kappa and mu-delta receptor complexes, which display novel pharmacology, coupling to effector systems and signaling regulation properties. Exciting new opportunities are arising from the recent characterization of these oligomeric receptors, with the potential to revolutionize opioid research and therapeutic targeting. PMID- 11786313 TI - Neuroimmunophilin ligands in the treatment of Parkinson's disease. AB - Parkinson's disease treatments can be divided into three categories: symptomatic, protective and restorative. This review focuses on the restorative and neuroprotective actions of a new class of potential therapeutic agents, neuroimmunophilin ligands. To date, however, short-term treatments with two such compounds in a non-human primate model and in patients with Parkinson's disease have been disappointing. PMID- 11786314 TI - Alzheimer's disease and the amyloid cascade hypothesis: ten years on. AB - The amyloid beta peptide as the major culprit of Alzheimer's disease pathogenesis entered the research arena about a decade ago. The amyloid cascade hypothesis was vividly discussed, supported and contested. Has it held up to all challenges until today? It is alive as ever. The recent identification of the key enzyme involved in amyloid beta generation offered a new target for drug discovery and a novel therapy approach using immunization has successfully eliminated plaque burden in a transgenic mouse. Neurofibrillary tangles, the other hallmark of the disease, were induced in an animal model by amyloid beta peptide. PMID- 11786315 TI - Neurotensin: an endogenous psychostimulant? AB - The neuropeptide neurotensin has been shown to be closely related to central dopaminergic regulation. Although emphasis has been put on its possible neuroleptic-like effects, more recent data--in particular with the use of non peptide neurotensin receptor antagonists--suggest instead a psychostimulant-like action of endogenous neurotensin. Such contradictory potential effects open an important debate on the possible therapeutic use of compounds related to neurotensin transmission. PMID- 11786316 TI - Neurotensin: an endogenous antipsychotic? AB - Despite evidence from a variety of experimental approaches implicating the neuropeptide neurotensin in both the mechanism of action of antipsychotic drugs and the pathophysiology of schizophrenia, there has been some debate as to whether a peripherally administered neurotensin receptor agonist represents a sound strategy for the development of a novel class of antipsychotic drugs. PMID- 11786317 TI - Endovascular brachytherapy in the prevention of vascular restenosis. AB - PURPOSE: To evaluate the technical feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: Ten patients with recurrence of stenosis in the femoropopliteal region underwent PTA followed by endovascular irradiation with Iridium-192 a high-dose rate after-loading technique. We used a single fraction of dose 12 Gy given in 3 mm from the source axis in the stenotic vessel segment. RESULTS: During follow-up of 59-580 days restenosis occurred in four patients 111, 460, 472 and 580 days after irradiation. All other patients are without restenosis. No radiation-associated side effects were observed. CONCLUSIONS: Endovascular brachytherapy of restenosis in the femoropopliteal region is technically feasible, and may be done as a part of the PTA. These encouraging results open the possibility of reduction of restenosis by the present method. PMID- 11786318 TI - Intraluminal 192Ir brachytherapy following transjugular intrahepatic portosystemic shunt revision: long-term results and radiotherapy parameters. AB - PURPOSE: The stenosis or occlusion of transjugular intrahepatic portosystemic shunt (TIPS) occurs in up to 75% of patients within 12 months after treatment. The aim of our investigation was to evaluate the feasibility, safety and efficacy of intraluminal high-dose rate brachytherapy (HDRBT) with Iridium-192 following TIPS revision to prevent restenosis due to pseudointimal hyperplasia. MATERIALS AND METHODS: Between September and November 1996, intraluminal BT was performed in five patients after TIPS revision. The indications for initial TIPS were a Budd-Chiari syndrome in two female patients and recurrent variceal bleeding by alcoholic liver cirrhosis in three male patients. TIPS was created with Wallstents (10 mm diameter in four patients) and Palmaz stent (10 mm diameter in one patient). The re-dilatation was done in all five patients 6 months after first stenting because of restenosis (>50% stent lumen reduction) or occlusion of the stent. A 5-French closed-tip, noncentered BT delivery catheter was used for subsequent radiotherapy. The whole length of the stent and performed dilatation (interventional length - IL) was taken as clinical target length (CTL). A 10-mm safety margin was added proximal and distal to the CTL due to uncertainties of BT source positioning, so forming the planning target length (PTL). To ensure that prescribed dose covers the whole PTL, the active source length (ASL) was 5 mm longer proximal and distal than PTL, so forming the reference isodose length (RIL). A dose of 12 Gy was prescribed in 3 mm distance from the source axis in the mid-plane of the applicator for three patients and in 5 mm distance for two patients. RESULTS: A normal patency (<50% lumen reduction) of the stent was achieved at 44 months follow-up (duplex sonography+portography) in all three patients with liver cirrhosis, whereas further revisions were necessary in two patients with Budd-Chiari syndrome (after 5.5 and 18 months). No acute, subacute or late brachytherapy (BT)-related side effects were seen until now. CONCLUSIONS: HDRBT following TIPS revision was safe and feasible in all patients. The exact impact of BT on the TIPS patency should be evaluated in larger clinical trials. Moderate dose escalation and use of today's commercially available centering radiation catheters seem to be necessary. PMID- 11786319 TI - Severe acute coronary spasm following intracoronary radiation for in-stent restenosis: a case report. AB - Intracoronary radiation therapy is currently the only available treatment for the prevention of recurrence of in-stent restenosis. We report a case of severe coronary spasm after excimer laser angioplasty, balloon angioplasty, and intracoronary gamma radiation in the right coronary artery (RCA) that resulted in an acute myocardial infarction. Treatment with 600 microg of intracoronary nitroglycerin resulted in minimal improvement; therefore, diltiazem 400 microg was administered intracoronary with total resolution of the spasm, restoring normal coronary blood flow without trace of acute dissection or thrombus inside the artery. PMID- 11786320 TI - Local arterial responses to 32P beta-emitting stents. AB - PURPOSE: 32P beta-emitting stents reduce neointimal growth in rabbit iliac arteries for at least 12 months after deployment but are associated with incomplete healing. The aim of this study was to quantitate arterial cellularity, with emphasis on the inflammatory response following radioactive stenting. METHODS: 32P beta-emitting stents were placed in rabbit iliac arteries and analyzed at 3 months (6 and 24 microCi), and 6 and 12 months (6, 24, and 48 microCi). Arterial cellular proliferation and cell densities of smooth muscle cells (SMC), mononuclear cells (macrophages and lymphocytes), and neutrophils (PMN) were determined. RESULTS: Total intimal cell density was greatest in control stents at all three time points, composed mostly of SMCs. SMC density associated with radioactive stents increased from 3 to 12 months but was significantly less than control nonradioactive stents. There was a 4-fold increase in cellular proliferation in the 24 and 48 microCi group vs. control stents. In the media, SMC density of radioactive stent groups was significantly reduced vs. control stents at all three time points, for all three activities. At 3, 6 and 12 months, there was a dose-dependent increase in intimal inflammatory cell density, which consisted mostly of macrophages. For 6-microCi stents inflammation peaked at 3 months and decreased thereafter. Inflammation for 24 microCi stents peaked at 6 months and then decreased at 12 months. Inflammation associated with 48-microCi stents remained high at 6 and 12 months. Focal atherosclerotic change was seen in 11% of stents in the 24-microCi group, and 37% and 50% in the 48-microCi group at 6 and 12 months, respectively. CONCLUSION: Intimal SMC density remains suppressed out to 12 months after placement of 32P beta-emitting stents. However, inflammation and cell proliferation remain increased and may potentially result in greater neointimal formation over time. PMID- 11786322 TI - A new treatment planning formalism for catheter-based beta sources used in intravascular brachytherapy. AB - Intravascular brachytherapy (IVBT) is an emerging modality for the treatment of atherosclerotic lesions in the artery. As part of the refinement in this rapidly evolving modality of treatment, the current simplistic dosimetry approach based on a fixed-point prescription must be challenged by future rigorous dosimetry method employing image-based three-dimensional (3D) treatment planning. The goals of 3D IVBT treatment planning calculations include (1) achieving high accuracy in a slim cylindrical region of interest, (2) accounting for the edge effect around the source ends, and (3) supporting multiple dwell positions. The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for gamma sources, as well as short beta sources with lengths less than twice the beta particle range. However, for the elongated beta sources and/or seed trains with lengths greater than twice the beta range, a new formalism is required to handle their distinctly different dose characteristics. Specifically, these characteristics consist of (a) flat isodose curves in the central region, (b) steep dose gradient at the source ends, and (c) exponential dose fall-off in the radial direction. In this paper, we present a novel formalism that evolved from TG-60 in maintaining the dose rate as a product of four key quantities. We propose to employ cylindrical coordinates (R, Z, phi), which are more natural and suitable to the slim cylindrical shape of the volume of interest, as opposed to the spherical coordinate system (r, theta, phi) used in the TG-60 formalism. The four quantities used in this formalism include (1) the distribution factor, H(R, Z), (2) the modulation function, M(R, Z), (3) the transverse dose function, h(R), and (4) the reference dose rate at 2 mm along the perpendicular bisector, D(R0=2 mm, Z0=0). The first three are counterparts of the geometry factor, the anisotropy function and the radial dose function in the TG 60 formalism, respectively. The reference dose rate is identical to that recommended by TG-60. The distribution factor is intended to resemble the dose profile due to the spatial distribution of activity in the elongated beta source, and it is a modified Fermi-Dirac function in mathematical form. The utility of this formalism also includes the slow-varying nature of the modulation function, allowing for more accurate treatment planning calculations based on interpolation. The transverse dose function describes the exponential fall-off of the dose in the radial direction, and an exponential or a polynomial can fit it. Simultaneously, the decoupling nature of these dose-related quantities facilitates image-based 3D treatment planning calculations for long beta sources used in IVBT. The new formalism also supports the dosimetry involving multiple dwell positions required for lesions longer than the source length. An example of the utilization of this formalism is illustrated for a 90Y coil source in a carbon dioxide-filled balloon. The pertinent dosimetric parameters were generated and tabulated for future use. PMID- 11786321 TI - The effect of ionizing irradiation on vasomotor reactivity in the rat thoracic aorta in vitro. AB - PURPOSE: Ionizing irradiation inhibits restenosis in animal models and human. Vasomotor tone preservation during and after radiation therapy is of clinical importance. We therefore investigated vascular reactivity following radiation therapy. METHODS AND MATERIALS: Wistar Sabra rats were treated with a single dose of 1000 cGy external X-ray irradiation. Vascular reactivity of 192 segments of rat thoracic aorta was studied in vitro in four groups (12 rats in each group, four segments from each aorta). Immediately after in vivo irradiation, immediately after ex vivo irradiation, 1 month after irradiation, and no irradiation (control). RESULTS: Vasoconstriction to phenylephrine (PE) 10(-9)-10( 5) M or KCl 118.0 mM in all the irradiated groups was similar to controls. Endothelium-dependent vasorelaxation to acetylcholine (ACh) 10(-9)-10(-5) M in segments studied immediately after in vivo irradiation was increased compared to controls at all concentrations (109.7+/-35. and 90.0+/-40.0%, respectively, at 10(-5) M, P=.006). Endothelium-independent relaxation to nitroglycerin 10(-9)-10( 5) M in all irradiated groups was similar to controls. CONCLUSIONS: External ionizing irradiation with 1000 cGy in the rat aortic model induces acute and transient increase in endothelium-dependent relaxation to ACh, and does not alter vasoconstriction and endothelium-independent relaxation. PMID- 11786323 TI - Dosimetry of source stepping for intravascular brachytherapy. AB - PURPOSE: Both beta and gamma sources of fixed length are currently used in the catheter-based intravascular brachytherapy (IVBT). Source stepping is often used to treat a lesion longer than the effective treatment length of the source. A major challenge for the stepping procedure is to attain a perfect dosimetric match (uniform dose) at the source junction. This work presents a quantitative and systematic dosimetric analysis for source stepping during an IVBT procedure. MATERIALS AND METHODS: The three most commonly used beta and gamma sources (192Ir by BEST, 90Sr by NOVOSTE and 32P by Guidant) were studied using the EGSnrc Monte Carlo code. Dose distributions were calculated for a perfect end-to-end match and for a range of end-to-end gaps and overlaps between consecutive steps. RESULTS: It is found that a perfect end-to-end match during source stepping yields uniform dose distribution in the region of source junction. The doses in the case of a mismatch (in the presence of an end-to-end gap or overlap) were found to be significantly different from those with the perfect end-to-end match. The dose deviation depends on the size of the gap or overlap, radial distance and type of source. The dose deviation decreases with radial distance for a given gap/overlap. For example, for a gap/overlap of 2 mm, dose decreases/increases of 30%, 55% and 60% were found at the radial distance of 2 mm from source for 192Ir, 90Sr and 32P, respectively. These dose deviations are reduced by approximately 10% when the radial distance increases from 2 to 3 mm. The dose deviations for gaps or overlaps in the range of 0-5 mm are presented. CONCLUSIONS: During an IVBT procedure involving source stepping, a perfect end-to-end match is always desired. Significant underdosing or overdosing can occur in the case of a source mismatch. A considerable caution should be exercised to ensure that sources are properly matched. PMID- 11786324 TI - Ytterbium-169: a promising new radionuclide for intravascular brachytherapy. AB - PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.0250%) was significantly reduced with adjunctive ICR (28% vs. 54%, P=.014). CONCLUSION: Radiation therapy with ELCA significantly reduces angiographic binary restenosis at 6 months in patients with diffuse ISR, driven predominantly by reduced percutaneous TVR. PMID- 11786327 TI - Reagentless biosensing using electrochemical impedance spectroscopy. AB - The use of electrochemical impedance spectroscopy (EIS) and the conducting polymer, poly (pyrrole), as an integrated recognition and transduction system for reagentless biosensor systems was demonstrated with two different systems. The first system being an immunoassay for detection of luteinising hormone (LH) with the antibody being entrapped with in the poly (pyrrole) matrix and the second, a construct for DNA hybridisation discrimination able to differentiate single- and double-stranded DNA based on the interaction of the DNA with poly (pyrrole). PMID- 11786328 TI - Single channel recordings of alpha-hemolysin reconstituted in S-layer-supported lipid bilayers. AB - Previous studies demonstrated that lipid membranes attached to a proteinaceous crystalline surface-layer (S-layer) revealed a prolonged lifetime and showed a reduced tendency to rupture in the presence of membrane active molecules. In addition, comparative studies on folded and S-layer-supported lipid membranes (SsLM) revealed an uniform capacitance of 0.64 +/- 0.04 microF/cm(2) for both composite membranes. In the present study, the feasibility to reconstitute the channel-forming protein alpha-hemolysin (alpha HL) into SsLM at single channel resolution was investigated. Single alpha HL channels could be recorded and the intrinsic properties like unitary conductance, current-voltage characteristics, and closure was found to be similar at both membranes. Thus, the tightly attached S-layer allowed complete reconstitution of alpha HL channels in SsLM. PMID- 11786329 TI - A novel enzyme biosensor for steroidal glycoalkaloids detection based on pH sensitive field effect transistors. AB - For the design of a biosensor sensitive to steroidal glycoalkaloids, pH-Sensitive Field Effect Transistors as transducers and immobilised butyrylcholinesterase as a biorecognition element have been used. The total potato glycoalcaloids can be measured by this biosensor in the concentration range 0.5-100 microM with detection limits of 0.5 microM for alpha-chaconine and of 2.0 microM for alpha solanine and solanidine, respectively. The responses of the developed biosensors were reproducible with a relative standard deviation of about 1.5% and 5% for intra- and inter-sensor responses (both cases, n=10, for an alkaloid concentration of 5 microM), respectively. Moreover, due to the reversibility of the enzyme inhibition, the same sensor chip with immobilised butyrylcholinesterase can be used several times (for at least 100 measurements) after a simple washing by a buffer solution and can be stored at 4 degrees C for at least 3 months without any significant loss of the enzymatic activity. PMID- 11786330 TI - Immobilisation of enzymes on poly(aniline)-poly(anion) composite films. Preparation of bioanodes for biofuel cell applications. AB - Immobilisation of enzymes is important for applications such as biosensors or biofuel cells. A poly(histidine) tag had been introduced on the C terminus of a lactate dehydrogenase enzyme. This mutant enzyme was then immobilised onto poly(aniline) (PANi)-poly(anion) composite films, PANi-poly(vinylsulfonate) (PVS) or PANi-poly(acrylate) (PAA). The NADH produced by the immobilised enzyme in the presence of beta-nicotinamide adenine dinucleotide (NAD(+)) and lactate is oxidised at the poly(aniline)-coated electrode at 0.05 to 0.1 V vs. saturated calomel electrode (SCE) at 35 degrees C. PMID- 11786331 TI - AC-magnetic field controlled drug release from magnetoliposomes: design of a method for site-specific chemotherapy. AB - Large unilamellar magnetoliposomes (MLs) with encapsulated doxorubicin (DOX) (anticancer drug) were prepared by reverse-phase evaporation. They were exposed to an alternating magnetic field with a frequency of 3.5 MHz and an induction of 1.5 mT produced in three-turn pancake coil. The results showed that magnetoliposomes could be specifically heated to 42 degrees C (phase transition temperature of a used lipid) in a few minutes and during this, the encapsulated doxorubicin is massively released. PMID- 11786332 TI - The design of dehydrogenase enzymes for use in a biofuel cell: the role of genetically introduced peptide tags in enzyme immobilization on electrodes. AB - The immobilization of the mutants of L-lactate dehydrogenase (LDH) on poly(aniline) (PANi) composite films has been investigated. Mutants possessing peptide tags of varying charge and nucleophilicity were created to probe the nature of the interaction between the protein and PANi. These results are significant for the development of a 'generic' approach to the immobilization of enzymes and other proteins. PMID- 11786333 TI - Electrode potential-controlled DNA damage in the presence of copper ions and their complexes. AB - Supercoiled (sc) DNA immobilized at the surface of a hanging mercury drop electrode was cleaved by reactive oxygen species generated by an electrochemically modulated reaction of copper ions, hydrogen peroxide and/or oxygen. The cleavage was observed in a certain potential region where redox cycling of DNA-bound Cu(II)/Cu(I) took place. In the presence of 1,10 phenanthroline the maximum efficiency of DNA cleavage was shifted to more negative potentials and the effect was enhanced. PMID- 11786334 TI - Bioelectrochemical application of some PQQ-dependent enzymes. AB - This paper focuses on the use of PQQ-dependent enzymes (PQQ enzymes) in amperometrical biosensors and gives emphasis on their innovative designs and applications. The study covers some aspects in the evolution of biosensors based on PQQ enzymes. Main attention is focused on the electrochemical properties of PQQ enzymes as very promising materials for the formation of electrochemical biosensors. Immobilization approaches and redox mediators recently used in PQQ enzymes based biosensors are reviewed. The acceptance of polypyrrole as a very promising immobilization matrix for some PQQ enzymes is discussed. PMID- 11786335 TI - Fluorescence studies on PAMAM dendrimers interactions with bovine serum albumin. AB - Polyamidoamine (PAMAM) dendrimers (generation 3.5 and 4) interaction with bovine serum albumin (BSA) was studied. The intensity of intrinsic fluorescence of two tryptophan residues and a shift in wavelength of their emission maxima were chosen as indicators of protein conformational changes. It is shown that the generation 4 has a greater impact on spectral properties of serum albumin than generation 3.5. PMID- 11786336 TI - Intermolecular biological electron transfer: an electrochemical approach. AB - We investigated the electron transfer (ET) rates between a well-defined gold electrode and cytochrome c immobilized at the carboxylic acid terminus of alkanethiol self-assembled monolayers (SAMs) by using the potential modulated electroreflectance technique. A logarithmic plot of ET rates against the chain length of the alkanethiol is linear with long chain alkanethiols. The ET rates become independent of the chain length with short alkanethiols. It is proposed that the rate-limiting ET step through short alkyl chains results from a configurational rearrangement process preceding the ET event. This "gating" process arises from a rearrangement of the cytochrome c from a thermodynamically stable binding form on the carboxylic acid terminus to a configuration, which facilitates the most efficient ET pathways (surface diffusion process). We propose that the lysine-13 of mammalian cytochrome c facilitates the most efficient ET pathway to the carboxylate terminus and this proposal is supported by the ET reaction rate of a rat cytochrome c mutant (RC9-K13A) [Elektrokhimiya (2001) in press], in which lysine-13 is replaced by alanine. The ET rate of K13A is more than six orders of magnitude smaller than that of the native protein. PMID- 11786337 TI - An evolutionary analysis of the reaction mechanisms of photosystem I reduction by cytochrome c(6) and plastocyanin. AB - Photosystem I reduction by the soluble metalloproteins cytochrome c(6) and plastocyanin, which are alternatively synthesized by some photosynthetic organisms depending on the relative availability of copper and iron, has been investigated in cyanobacteria, green algae and plants. The reaction mechanism is classified in three different types on the basis of the affinity of the membrane complex towards its electron donor protein. The role of electrostatic interactions in forming an intermediate transient complex, as well as the structural and functional similarities of cytochrome c(6) and plastocyanin are analysed from an evolutionary point of view. The proposal made is that the heme protein was first "discovered" by nature, when iron was much more abundant on the Earth's surface, and replaced by plastocyanin when copper became available because of the oxidizing conditions of the new atmosphere. PMID- 11786338 TI - Estimation of electrochrome dyes position in the bilayer through the 2nd harmonic of capacitive current. AB - The depth of location of electrochrome dyes RH-type in a bilayer is evaluated using the magnitudes of intramembrane field Delta phi measured by two methods: from relative change of the rate of transmembrane transport of hydrophobic ions and by means of electrostriction method based on the compensation of the 2nd harmonic of capacitive current, which is generated due to electrostriction phenomenon if sine voltage is applied to the bilayer. The experiments and theoretical analysis are conducted. Comparing the theoretical curves for Delta phi measured by the both methods and the experimental data, the depth of location was estimated as follows: 0.7-1 nm for the dyes RH-421 and RH-160, and 0.9-1.15 nm for the dye RH-237. PMID- 11786339 TI - Fluidity gradient of erythrocyte membranes in diabetics: the effect of resorcylidene aminoguanidine. AB - We estimated in vitro membrane fluidity gradient in erythrocytes (RBC) from diabetic patients, using a fluorescent dye 1,6-diphenyl-1,3,5-hexatriene (DPH). The rate constant of DPH incorporation (k) into the membranes was determined by fitting experimental data to an exponential equation. Four important findings were made. First, membrane fluidity in the hydrocarbon region of RBC from diabetic patients is decreased compared with control cells (P<0.01). Second, the rate constant k of DPH incorporation into the membranes of RBC from diabetic patients was lower (P<0.01), which indicates an altered fluidity gradient in the membranes. Third, resorcylidene aminoguanidine (RAG) decreased significantly (P<0.001) the anisotropy values in RBC membranes from diabetic patients, which means that it apparently acted as a fluidizing agent. Lastly, no significant differences in the rate constants k were found between the control membranes (from RAG untreated RBC) and the membranes isolated from RAG pretreated blood from diabetic patients, as well as between the control membranes and those from RAG pretreated control blood. In conclusion, RAG affects lipid-protein interactions in RBC membranes, which results in membrane lipid bilayer fluidization and leads to the restoration of natural physiological membrane dynamic parameters in RBC from diabetic patients. PMID- 11786340 TI - Affinity interactions on a liposome surface detected by ultrasound velocimetry. AB - In this work, we performed targeted immobilization of immunoglobulins by means of bacterial S-layer proteins from Bacillus coagulans E38-66/V1 recrystallized on liposomes, which were exploited as immobilization matrix for antibody (Ab)-human IgG. The study of interaction of rabbit or swine anti-human IgG as antigens (Ag) was performed by means of measuring changes of ultrasound velocity. We showed that at a temperature of 25 degrees C, the increment of ultrasound velocity [u] linearly decreased following an increase of concentration of Ag. The decrease of [u] was presumably due to changes of hydration of the membrane due to the binding process. Approximately 10 times lower changes of [u] were observed at 45 degrees C for Ag-Ab interaction as well as for nonspecific interaction of Ag with liposomes covered by S-layer without Ab. No substantial differences in the behaviour of [u] were observed for interactions of human IgG with rabbit or swine anti-human IgG. PMID- 11786341 TI - Electrochemical oxidation mechanism of guanine and adenine using a glassy carbon microelectrode. AB - The electrochemical oxidation mechanism of guanine and adenine was investigated using a glassy carbon microelectrode and cyclic and differential pulse voltammetry. It is pH-dependent and the electron transfer process occurs in consecutive steps with the formation of strongly adsorbed dimers on the electrode surface for both compounds. PMID- 11786342 TI - Scanning probe microscopic imaging of guanine on a highly oriented pyrolytic graphite electrode. AB - Guanine adsorbed onto a highly oriented pyrolytic graphite electrode was studied by MAC-Mode Atomic Force Microscopy (AFM), and the electrochemical behaviour of the guanine layer was investigated with Electrochemical AFM. Guanine adsorbs spontaneously, without forming a well-packed structure, into nucleation spots, which are stable with time and cover the surface uniformly and almost completely. The process of guanine adsorption and nucleation can be controlled and the effect of altering the exposure time and varying the potential was investigated. PMID- 11786343 TI - A dynamic method of measuring surface potential change due to binding of bitter substance at monolayer-coated liquid membrane surface. AB - A dynamic method of determining the membrane surface potential change due to a binding of a hydrophobic ion has been presented. The surface potential was determined from the time course of membrane potential under zero electric current during a transition between two steady states in a membrane filter impregnated with a phospholipid and 1-octanol. One of the alkaloids, quinine hydrochloride, was used as a hydrophobic electrolyte. Surface charge density and equilibrium constant for binding of quinine ions with ionizable groups of the phospholipids at the membrane surface were determined from the surface potential according to the Poisson-Boltzmann equation. PMID- 11786344 TI - Ion channels in the human red blood cell membrane: their further investigation and physiological relevance. AB - Using the patch-clamp technique, two different ion channels have been characterized further in the human red blood cell (RBC) membrane. We demonstrate that the non-selective cation channel (NSC) is permeable to Ca(2+) and can be activated by prostaglandin E(2) (PGE(2)). Therefore, the physiological role of this channel could be, together with the Ca(2+)-activated K(+) channel, the participation in the process of blood clot formation. We give also evidence that another channel in the RBC membrane, so far assumed to be a small conductance anion channel, is more likely to be a proton or a hydroxyl ion channel. PMID- 11786345 TI - Polyaniline-modified cholinesterase sensor for pesticide determination. AB - Cholinesterase sensors based on glassy carbon and planar epoxy graphite electrodes modified with processed polyaniline have been developed and examined for pesticide detection. The modification of electrode surface with polyaniline provides high operational stability and sensitivity towards the pesticides investigated. The detection limits found (coumaphos, 0.002, trichlorfon, 0.04, aldicarb, 0.03, methiocarb, 0.08 mg l(-1)) make it possible to detect the pollutants in the waters on the level of limited threshold levels without sample preconcentration. PMID- 11786346 TI - Development of enzyme biosensor based on pH-sensitive field-effect transistors for detection of phenolic compounds. AB - This article describes a biosensor based on pH-sensitive field-effect transistors (pH-FETs) as transducer, and immobilised enzyme tyrosinase as biorecognition element, which was used for the determination of phenolic compounds in water solutions. The biologically active membrane was formed by cross-linking of tyrosinase with bovine serum albumin (BSA) in saturated glutaraldehyde (GA) vapours on the sensitive transducer surface. The main analytical characteristics were studied under different conditions as well as the possibility to optimise these working parameters. Different factors such as the pH of immobilisation, the enzyme loading, the time of exposition to glutaraldehyde vapours were investigated in regards to the influence on sensitivity, limit of detection, dynamic range, and operational and storage stability. PMID- 11786347 TI - Effect of pH on direct electron transfer in the system gold electrode-recombinant horseradish peroxidase. AB - The effect of pH on the kinetics of the bioelectrocatalytic reduction of H(2)O(2) catalysed by horseradish peroxidase (HRP) has been studied at -50 mV vs. Agmid R:AgCl on HRP-modified Au electrodes placed in a wall-jet flow-through electrochemical cell. Native HRP (nHRP) and a nonglycosylated recombinant form containing a six-histidine tag at the C-terminus, C(His)rHRP, produced by genetic engineering of nonglycosylated recombinant HRP using an E. coli expression system, have been used for adsorptive modification of Au electrodes. A favourable adsorption of C(His)rHRP on pre-oxidized Au from a protein solution at pH 6.0 provided a high and stable current response to H(2)O(2) due to its bioelectrocatalytic reduction based on direct (mediator-less) electron transfer (ET) between Au and the active site of HRP. The heterogeneous ET rate constant, k(s), calculated from experimental data on direct ET, on mediated ET in the presence of catechol as well as from microbalance data, increased more than 30 times when changing from nHRP to C(His)rHRP. For both forms of HRP, the increasing efficiency of bioelectrocatalysis with increasing [H(3)O(+)] was observed. The values of the apparent k(s) between C(His)rHRP and Au changed from a value of 12+/-2 s(-1) in PBS at pH 8.0 to a value of 434+/-62 s(-1) at pH 6.0; a similar k(s)-pH dependence was also observed for nHRP, providing the possibility to consider the reaction mechanism involving the participation of a proton in the rate-determining step of the charge transfer. PMID- 11786348 TI - Bacterial flagellar motor and H(+)/ATP synthase: two proton-driven rotary molecular devices with different functions. AB - Both the bacterial flagellar motor and the H(+)/ATP synthase are membrane-bound macromolecular complexes in which the movement of protons through channels across the membrane is coupled to the rotation of a part of the complex around an axis perpendicular to the membrane. Despite this similarity, the two devices are designed for quite different functions. The flagellar motor is responsible for a practically smooth rotation of the flagellar filament in order to propel the cell. Smooth rotation is not essential for the H(+)/ATP synthase, which accumulates torque by twisting a rod-shaped structure. Possible mechanisms for generating torque in the two devices are presented, based on the models which have been proposed. The performances of the various mechanisms are discussed. PMID- 11786349 TI - Designing membrane electrochemical reactors for oxidoreductase-catalysed synthesis. AB - The purpose of this work was to design an electrochemical reactor to enhance the high selectivity of enzyme-catalysed processes. In order to develop economically efficient syntheses, the enzymes must be confined in the strict vicinity of the electrode surface. Here the confinement was achieved with a dialysis membrane in a so-called Dialysis-Membrane Electrochemical Reactor (D-MER). Oxidation of glucose into gluconic acid catalysed by glucose oxidase was a first example. The ADH-catalysed reduction of cyclohexanone into cyclohexanol was also tested in a new type of MER. NADH was electrochemically regenerated thanks to mediator (methyl viologen or rhodium complex). The key point in developing electro enzymatic process is to ensure the perfect fitting of the reactor design to the reactions that are to be processed. PMID- 11786350 TI - Transient dielectro-deformations of erythrocyte governed by time variation of cell ionic state. AB - The possibility is shown to monitor the transient ionic state and volume of erythrocyte suspended in low ionic strength solution (LISS) by registration of the dielectro-deformation (DD) of a cell. The adequate theoretical basis is developed. Possible registration modes are considered analytically and numerically using the theory of dielectro-deformation of erythrocytes developed previously. PMID- 11786351 TI - Electrochemotherapy of horses. A preliminary clinical report. AB - Sarcoids are skin spontaneous tumours detected in horses. It can be cured by chemotherapy by using cisplatin. A multisequence treatment must be performed. Problems are present due to the poor diffusion of the hydrophilic product in the tumours. Electropulsation is known to drastically enhance the effect of antitumoral drugs in vivo. Taking into account the very successful results of the group in Ljubljana (Slovenia), we started a research clinical program where electropulsation was applied after local cisplatin injection. The size of sarcoids is large (several centimeters). A specially designed set of wire contact electrodes was built. The distance between the electrodes was 0.9 cm and their length was 0.9 cm. The contact with the skin was obtained by a conductive paste. A PS15 Jouan Electropulsator was used to deliver eight pulses of 0.1 ms at a 1-Hz frequency with a 1.3-kV voltage. The animal was anesthesized. Intratumoral cisplatin injections were operated every 0.6 cm (0.2 ml at a 1-mg/ml concentration). Five minutes after the first drug injection, multiple electrotreatments were applied by moving the electrodes between the pulse applications. This allows the treatment of all the tumour surface. Several successive treatments were performed with a delay of 2 weeks between each. All lesions completely responded. The sarcoids disappear after only 2 or 3 electrochemotherapies. Objective responses were obtained in 100% of the treated lesions. All horses tolerated the treatment well. No adverse effect from the electric pulses was observed even in the case of a high number of pulses, or when several consecutive treatments were applied. No regrowth was observed in the 18 months follow-up period. PMID- 11786352 TI - Recent biotechnological developments of electropulsation. A prospective review. AB - During the last 25 years, basic research has improved our knowledge on the molecular mechanisms triggered at the membrane level by electric pulses. Applied aspects may now be used under safe conditions. Electropulsation is known as a very efficient tool for obtaining gene transfer in many species to produce genetically modified organisms (GMO). This is routinely used for industrial purposes to transfer exogenous activities in bacteria, yeasts and plants. The method is simple and of a low cost. But electropulsation is not limited to this application for biotechnological purposes. It is known that the field-associated membrane alterations can be irreversible. The pulsed species cannot recover after the treatment. Their viability is strongly affected. This appears as a very promising technology for the eradication of pathogenic microorganisms. Recent developments are proposed for sterilization purposes. New flow technologies of field generation allow the treatment of large volumes of solution. When high flow rates are used, microorganisms are submitted both to a hydromechanical and to an electrical stress. The synergy of the two effects may be present when suitable pulsing conditions are chosen. Several examples for the treatment of domestic water and in the food industry are described. Walled microorganisms are affected not only at the membrane level. We observed that alterations are present on the cell wall. A very promising technology is the associated controlled leakage of the cytoplasmic soluble proteins. Large dimeric proteins such as beta galactosidases can be extracted at a high yield. High volumes can be treated by using a flow process. Extraction of proteins is obtained with many systems including mammalian cells. PMID- 11786353 TI - Oxidative behaviour of apomorphine and its metabolites. AB - The metabolism of apomorphine is quite complex due to interactions with proteins and other tissue components that affect its pharmacokinetic profile. The electrochemical oxidation mechanism of apomorphine and of some synthesised apomorphine derivatives was studied. It was found to be related to the reaction of o-diphenol and tertiary amine groups and strongly dependent on pH. PMID- 11786354 TI - Determination of glutathione-S-transferase traces in preparations of p53 C terminal domain (aa320-393). AB - Tumor suppressor protein p53 is often expressed as a fusion protein with glutathione-S-transferase (GST). The sensitive determination of GST in p53 samples is thus necessary. We propose a method for the determination of traces of GST in the p53 C-terminus based on the constant current chronopotentiometric stripping analysis (CPSA) with hanging mercury drop electrode (HMDE). GST produces a catalytic signal in cobalt-containing solutions due to cysteine residues. A large excess of the C-terminus does interfere with the determination because of the lack of cysteines in the molecule. This method is simple and very sensitive and is capable of detecting <1% GST in the p53 sample. PMID- 11786355 TI - Determination of nanogram quantities of osmium-labeled single stranded DNA by differential pulse stripping voltammetry. AB - Earlier, we showed that using differential pulse cathodic stripping voltammetry with hanging mercury drop electrode (HMDE), single-stranded (ss) DNA modified with osmium tetroxide, pyridine reagent (Os,py) can be determined at concentrations down to about 10-5 ng/ml. Here, we show that by exchanging Os,py for osmium tetroxide, 2,2'-bipyridine (Os,bipy) and decreasing the pH of the background electrolyte from neutrality to about pH 4, ssDNA can be determined at concentrations lower by one order of magnitude. Determination of DNA at such low concentrations may find use in various areas of molecular biology and in biotechnologies, including the development of DNA sensors. PMID- 11786356 TI - Strategic issues in reliable sensing. AB - Amperometric enzyme biosensors must possess two important characteristics if they are to be successfully utilised as reliable monitoring devices. They must exhibit linearity over concentrations relevant to the target analyte, and they must avoid contamination, adverse reactions with the sample matrix response to interferents that react directly at the polarised working electrode surface. Covering polymeric membranes have provided a useful route to overcoming these problems. This report summarises successful modulation of membrane bulk as well as surface properties using surfactant-loaded diffusion limiting PVC and phenolic membranes, and the possible exploitation of direct response conducting poly (pyrrole) membrane loaded with affinity molecules through impedance spectroscopy. PMID- 11786357 TI - Adsorption of differently charged forms of horseradish peroxidase on metal electrodes of different nature: effect of surface charges. AB - The adsorption and bioelectrocatalytical activity in the reaction of H(2)O(2) reduction of two forms of horseradish peroxidase (HRP) offering different surface charges at pH 6.0 were studied on gold and silver electrodes. Positively charged HRP was assessed at pH 6.0 for the case of native HRP (isoenzyme C, pI=8.8), and negatively charged HRP for the case of native HRP exposed to previous oxidation of carbohydrate residues and further introduction of sulfonate groups (pI=5.0). Under oxidative pretreatment, the gold electrode surface was considered to be negatively charged. Data on the direct immobilisation of HRPs on the bare gold surfaces were estimated with quartz crystal microbalance and data on bioelectrocatalytical activity of peroxidases on gold and silver electrodes were obtained in the course of direct and mediated amperometric detection of H(2)O(2). The presented results demonstrate that the surface charges of both the enzyme and the electrode play a dominant role in the immobilisation and, thereby, in the efficiency of the bioelectrocatalytical processes. PMID- 11786358 TI - Elimination voltammetry of nucleic acids on silver electrodes. AB - A newly developed electrochemical method--Elimination Voltammetry with Linear Scan (EVLS)--has been applied to the electrochemical study of nucleic acids (NAs) on a silver electrode. Using the linear combination of the currents measured at different scan rates, the EVLS is capable of eliminating one or two selected particular currents. It was shown that the elimination function conserving the reversible diffusion current and eliminating the charging and kinetic currents provides the significant increase of voltammetric signals of DNA. Due to the high sensitivity and resolution power, the EVLS can contribute to study behaviour of nucleic acids on the charged interface and can be applied to nucleic acid analyses and the development of DNA sensors. PMID- 11786359 TI - P680: what is it and where is it? AB - Electron and X-ray crystallography have provided intermediate structural models for photosystem II (PSII), the membrane located multisubunit complex which uses light energy to split water into its elemental constituents. This reaction is thermodynamically demanding and involves the production of redox potentials in excess of 1 V. Structural analyses have now shown that the primary oxidant, P680, is not a 'special pair' of chlorophylls, as in other types of photosynthetic reaction centres, but a tetramer of equally spaced chlorophyll a molecules. Its high redox potential, and the involvement of four weakly coupled isoenergetic monomers rather than a strongly excitonically coupled 'special pair', has implications for redox mechanisms which are unique to PSII, and therefore not found in any other photosynthetic system. The importance of these features is discussed. PMID- 11786360 TI - Electron transfer dynamics of cytochrome c bound to self-assembled monolayers on silver electrodes. AB - Cytochrome c (Cyt-c) was electrostatically immobilised on Ag electrodes coated with self-assembled monolayers (SAM) that are formed by omega-carboxyl alkanethiols with different alkyl chain lengths (C(x)). Surface enhanced resonance Raman (SERR) spectroscopy demonstrated that electrostatic binding does not lead to conformational changes of the heme protein under the conditions of the present experiments. Employing time-resolved SERR spectroscopy, the rate constants of the heterogeneous electron transfer (ET) between the adsorbed Cyt-c and the Ag electrode were determined for a driving force of zero electronvolts. For SAMs with long alkyl chains (C(16), C(11)), the rate constants display a normal exponential distance dependence, whereas for shorter chain lengths (C(6), C(3), C(3)), the ET rate constant approaches a constant value (ca. 130 s(-1)). The onset of the non-exponential distance-dependence is paralleled by an increasing kinetic H/D effect, indicating a coupling of the redox reaction with proton transfer (PT) steps. This unusual kinetic behaviour is attributed to the effect of the electric field at the Ag/SAM interface that increasingly raises the energy barrier for the PT processes with decreasing distance of the adsorbed Cyt c from the electrode. The distance-dependence of the electric field strength is estimated on the basis of a simple electrostatic model that can consistently describe the redox potential shifts of Cyt-c as determined by stationary SERR spectroscopy for the various SAMs. At low electric fields, PT is sufficiently fast so that rate constants, determined as a function of the driving force, yield the reorganisation energy (0.217 electronvolts) of the heterogeneous ET. PMID- 11786361 TI - Electrosynthesis of poly-o-diaminobenzene on the Prussian Blue modified electrodes for improvement of hydrogen peroxide transducer characteristics. AB - Electropolymerisation of nonconducting polymer, poly-(1,2-diaminobenzene) on the top of Prussian Blue (PB) modified electrode led to significant improvement of resulting hydrogen peroxide transducer selectivity and operational stability. The reported transducer retained 100% of response during 20 h under the continuous flow of 0.1 mM H(2)O(2), and thus improves the stability level in selective peroxide detection by one order of magnitude. The selectivity value of the PB poly(1,2-DAB) based H(2)O(2) sensor in relation to ascorbate is approximately 600. No signals to acetaminophen and urate were investigated. PB-poly(1,2 diaminobenzene) modified electrode allows the detection of H(2)O(2) in the flow injection mode down to 10(-7) M with the sensitivity 0.3 A M(-1) cm(-2), which is only two times lower compared to the uncovered PB based transducer. PMID- 11786362 TI - Stabilization of ferrocene leakage by physical retention in a cellulose acetate membrane. The fructose biosensor. AB - The prevention of ferrocene leakage from an electrode by physical retention of mediator in a matrix of cellulose acetate membrane is reported. Five types of the cellulose acetate membranes were prepared, containing 1.8%, 5.3%, 8.5%, 20.0% of ferrocene and a membrane containing 1.8% of ferrocene and 0.05 % of Nafion in the matrix. Ferrocene embedded membranes were successfully applied in the construction of a fructose biosensor by immobilization of PQQ-dependent fructose dehydrogenase (FDH). The biosensor comprising a cellulose acetate membrane with 1.8% of ferrocene and 0.05% of Nafion had good stability characteristics, retained almost 40% of the initial response after 8 h of continuous use with an initial sensitivity of 226 nA mM(-1) and response time of 75 s. PMID- 11786363 TI - Surface modified microelectrodes for selective electroanalysis of metal ions in environmental components. AB - The surface modification of electrodes was achieved by the Langmuir-Blodgett technique. The monolayers of laponite clay and polythiophene were formed at the air-water interface and these films were then transferred onto carbon microelectrodes. The behaviour of both untreated and coated electrodes was tested by originally developed double-step voltcoulometry (DSVCM). The dependence of charge response on the concentration of Cu(2+) species was investigated. Straight calibration curves were obtained and enhanced sensitivity of coated electrodes was documented. It is shown that the accumulation of Cu ions into laponite clay was maintained even after transferring the electrode into a pure water. The characteristic features of the "memory effect" are discussed. PMID- 11786364 TI - Direct electrochemistry of catalase on glassy carbon electrodes. AB - Catalase was investigated as a possible catalyst of the electrochemical reduction of oxygen on glassy carbon electrodes. The presence of catalase dissolved in solution only provoked a moderate current increase, which was fully explained by the catalase-catalysed disproportionation of hydrogen peroxide (Scheme I). When catalase was adsorbed from dimethylsulfoxide on the surface of electrodes that did not undergo any electrochemical pre-treatment (EP), catalase efficiently catalysed oxygen reduction via direct electron transfer from the electrode (Scheme II). The results are discussed with respect to the electrode surface properties and the enzyme structure. PMID- 11786365 TI - Effects of low-frequency magnetic fields on bacteria Escherichia coli. AB - The effects of low-frequency magnetic fields (Bm=2.7-10 mT, f=50 Hz, time of exposure t=0-12 min, laboratory temperature) on the viability and oxidoreductive activity of gram-negative bacteria Escherichia coli were investigated. The growth of these bacteria was negatively affected by such fields. We compared two experimental systems--solenoid [Sb. Lek. 99 (1998) 455] and a cylindrical spool- to find differences between nonhomogeneous and "more homogeneous" magnetic fields. We observed analogous effects in both experimental conditions. The growth curve of the exposed bacteria was lower than the control one. The ability of bacteria to form colonies decreased with increasing magnetic field intensity and with increasing time of exposure. The oxidoreductive activity was measured using reduction of a tetrazolium salt. The decrease in oxidoreductive activity with increasing time of exposure was observed, but the effect was due to a lower amount of bacteria surviving the exposure to the magnetic fields. The decrease in oxidoreductive activity and ability to form colonies were compared with the assumption that the effect of magnetic field is probably bactericidal. PMID- 11786366 TI - Cyclic voltammetry of echinomycin and its interaction with double-stranded and single-stranded DNA adsorbed at the electrode. AB - Interactions of echinomycin (Echi) with DNA was studied by cyclic voltammetry (CV) with hanging mercury drop electrode (HMDE). Echinomycin was electrochemically active, yielding several signals. Interaction of Echi with dsDNA attached to a hanging mercury drop electrode resulted in high Echi signals, suggesting a strong binding of Echi to dsDNA by bis-intercalation at the electrode surface. Under the same conditions, interaction of Echi with ssDNA produced almost no Echi signal. This behavior is in agreement with a strong binding of Echi to dsDNA and a very weak binding of Echi to ssDNA observed earlier in solution. Echi, thus, appears to be a good candidate for redox indicator in electrochemical DNA hybridization sensors. PMID- 11786367 TI - Direct and electrically wired bioelectrocatalysis by hydrogenase from Thiocapsa roseopersicina. AB - Hydrogen enzyme electrodes based on direct and mediated bioelectrocatalysis were developed. Direct bioelectrocatalysis of hydrogen oxidation/evolution was observed for hydrogenase adsorbed on carbon filament material. The equilibrium hydrogen potential was achieved on mediatorless hydrogen enzyme electrodes in hydrogen atmosphere. The electrocatalytic activity of hydrogenase in direct bioelectrocatalysis of hydrogen oxidation was two orders of magnitude higher compared to platinum. The reported electrode remained 50% activity after 6 months of storage with periodical testing. Wired bioelectrocatalysis was achieved by adsorption of hydrogenase onto electropolymerized redox mediator N-methyl-N'-(12 pyrrol-1-yl-dodecyl)-4,4'-bipyridinium ditetrafluoroborate. PMID- 11786368 TI - Interaction of merocyanine 540 with charged membranes. AB - In this work, phospholipid liposomes were used to investigate the influence of lipid negative charge on the interaction of merocyanine 540 (MC540) with model membranes. Liposomes were prepared from a mixture of neutral dimyristoyl lecithin (DMPC) and negatively charged dimyristoyl phosphatidic acid (DMPA). A strong dependence between the presence of charges on the membrane and dye association was found. The affinity of the dye to liposomes was decreased with an increasing content of DMPA in liposomes. Changes in absorption spectra of MC540 suggest that the decrease in affinity of MC540 to charged membranes is accompanied by a hypsochromic solvatochromic shift and changes in monomer/dimer equilibrium of MC540 incorporated in the membrane. PMID- 11786369 TI - STM study of morphology and electron transport features in cytochrome c and nanocluster molecule monolayers. AB - The morphology and electron tunneling through single cytochrome c and nanocluster Pt(5)(CO)(7)[P(C(6)H(5))](4) molecules organized as monolayer Langmuir-Blodgett (LB) films on graphite substrate have been studied experimentally using scanning tunneling microscopy (STM) and spectroscopy techniques with sub-nanometer spatial resolution in a double barrier tunnel junction configuration STM tip monomolecular film-conducting substrate at ambient conditions. STM images of the films revealed globular structures with characteristic diameters (approximately 3.5 nm for the protein molecule and approximately 1.2 nm for the nanocluster). The spectroscopic study by recording the tunneling current-bias voltage (I-V) curves revealed tunneling I-V characteristics with features as steps of different width and heights that are dependent on the STM tip position over the molecule in the monolayer, giving evidence for sequential discrete electron-tunneling effects with the combination of the single electron Coulomb-charging energy and the electronic energy level separation (molecular spectrum) in such immobilized metalloprotein and nanocluster structures that can be of interest for the development of bioelectronic and hybrid functional nanosystems. PMID- 11786370 TI - GH as a co-gonadotropin: the relevance of correlative changes in GH secretion and reproductive state. AB - It is now well established that exogenous GH promotes sexual maturation and reproductive function. The possibility that this may reflect physiological actions of endogenous GH has, however, rarely been considered. Correlative changes in GH secretion and reproductive state (puberty, pregnancy, lactation, menopause and ovarian cycles) are thus the primary focus of this review. GH secretion is, for instance, elevated during major transitions in reproductive status such as puberty and pregnancy. In some cases, augmented circulating GH levels are paired with hepatic GH resistance. This interaction may permit selective activation of gonadal responses to GH without activating IGF-I-mediated systemic responses. This selective activation may also be mediated by autocrine, paracrine or intracrine GH actions, since GH is also synthesized in reproductive tissues. Correlative changes in GH secretion and reproductive state may be mediated by events at the hypothalamic, pituitary and gonadal level. In addition to direct effects on gonadal function, GH may influence reproductive activity by increasing gonadotropin secretion at the hypothalamic and pituitary level and by enhancing gonadotropin responsiveness at the gonadal level. The close association between reproductive status and the somatotrophic axis supports the physiological importance of GH in reproductive function. PMID- 11786371 TI - Development and validation of a new monoclonal antibody to mammalian aromatase. AB - The biosynthesis of oestrogens from androgens is catalysed by the aromatase complex, an essential component of which is the aromatase cytochrome P450 (P450 arom) protein. Expression of a functional P450 arom is essential for normal fertility in males and females and the sequence of the protein is highly conserved. We have raised a new monoclonal antibody against a conserved peptide and validated it on fixed tissue sections of the rat, common marmoset (Callthrix jacchus) and human. The monoclonal antibody was used successfully for Western analysis and specifically reacted with a 55 kDa protein in microsomal extracts. On sections of ovaries in all three species, expression in follicles was specific to the mural granulosa cells of antral follicles and was present in corpora lutea. In the human and marmoset, staining of luteal cells was markedly heterogeneous and did not appear to vary consistently with the stage of the cycle. The intensity of immunostaining was elevated in corpora lutea from pregnant rats and following human chorionic gonadotropin rescue in the human. In the testis, the highest levels of expression were observed in the Leydig cells within the interstitium. In adult rat and marmoset, and possibly also in the human, some P450 arom was associated with the cytoplasm surrounding elongate spermatids but other germ cells were immunonegative. In conclusion, a new monoclonal antibody specific for P450 arom recognises the protein in rodent, primate and human. Its ability to work on fixed tissue sections will facilitate identification of individual cells expressing P450 arom within complex tissues. PMID- 11786372 TI - Retinoic acids promote the action of aromatase and 17beta-hydroxysteroid dehydrogenase type 1 on the biosynthesis of 17beta-estradiol in placental cells. AB - The biosynthesis of 17beta-estradiol (E(2)) in human placenta involves the actions of aromatase and 17beta-hydroxysteroid dehydrogenase type 1 (17HSD1). Aromatase, an enzyme complex comprised of P450aromatase (P450arom) and NADH cytochrome P450 reductase, converts androgens to estrogens, whereas 17HSD1 catalyzes the reduction of estrone to E(2). In the present study, the effects of retinoic acids (RAs) on P450arom and 17HSD1 expression in placental cells were investigated. Treatment with all-trans-RA (at-RA) or 9cis-RA increased E(2) production in JEG-3 choriocarcinoma cells and cytotrophoblast (CTB) cells isolated from normal early placentas. Meanwhile, the activity of aromatase and expression of P450arom mRNA were induced by at-RA in JEG-3 cells. Northern blot analysis showed that the effect on P450arom mRNA expression occurs in a dose- and time-dependent fashion. Similar to at-RA and 9cis-RA, Ro40-6055, the retinoic acid receptor alpha (RARalpha)-selective activator, increased the expression of P450arom and 17HSD1 mRNA in JEG-3 cells. On the other hand, Ro41-5253 (Ro41), the RARalpha-selective antagonist, blocked the stimulatory effect of RAs on P450arom expression. Surprisingly, Ro41 induced the activity and mRNA expression of 17HSD1 in JEG-3 cells, which is in contrast to the expected inhibitory effect and, moreover, remarkably potentiated the induction by at-RA and 9cis-RA. However, reporter gene analysis revealed that the influence of Ro41 on the transcription of the HSD17B1 gene, which encodes 17HSD1, is considerably milder in JEG-3 cells, and it only additively enhanced the effect of at-RA. Finally, it was found that at-RA and 9cis-RA increased the expression of P450arom and 17HSD1 mRNA in CTB cells, but to a lesser extent. The data suggest that RAs may play a role in promoting the biosynthesis of E(2 )in the placenta. In addition, Ro41 has divergent effects on gene expression in JEG-3 cells. PMID- 11786373 TI - Laminin-alpha6beta1 integrin interaction enhances survival and proliferation and modulates steroidogenesis of ovine granulosa cells. AB - This study aimed to determine the physiological role of laminin (LN) and its receptor, alpha(6)beta(1) integrin, in controlling the functions of granulosa cells (GC) during follicular development in sheep ovary. Immunohistochemistry experiments showed the presence of increasing levels of LN (P<0.0001), and high levels of mature alpha(6)beta(1) integrin in GC layers of healthy antral follicles during the follicular and the preovulatory phases of the estrous cycle. In vitro, the addition of a function-blocking antibody raised against alpha(6) subunit (anti-alpha(6) IgG) to the medium of ovine GC cultured on LN impaired cell spreading (P<0.0001), decreased the proliferation rate (P<0.05) and increased the apoptosis rate (P<0.05). Furthermore, addition of anti-alpha(6) IgG enhanced estradiol (E2) secretion by GC in the presence or absence of follicle stimulating hormone (FSH), luteinizing hormone or insulin-like growth factor-I in culture medium (P<0.0001), and inhibited progesterone (P4) secretion in basal conditions or in the presence of low (0.5 ng/ml) FSH concentrations only (P<0.0001). The anti-alpha(6) IgG effect was specific to an interaction of LN with alpha(6)beta(1) integrin since it was ineffective on GC cultured on heat denatured LN, RGD (arginine-glycine-aspartic acid) peptides and non-coated substratum. Hence, this study established that alpha(6)beta(1) integrin 1) was expressed in GC of antral follicles, 2) mediated the actions of LN on survival, proliferation and steroidogenesis of GC, and 3) was able to dramatically modulate P4 and E2 secretion by GC in vitro. It is suggested that during the follicular and the preovulatory phases of the estrous cycle, the increasing levels of LN in GC of large antral follicles might support their final development to ovulation. PMID- 11786374 TI - Effect of prolactin and dopaminergic drugs on uterine response to chronic estrogen exposure. AB - The aim of this work was to examine the role of prolactin and dopaminergic drugs, which affect prolactin secretion, on proliferative and morphogenetic reactions in the uterus under continuous estrogen treatment. Ovariectomized mice received injections of estradiol dipropionate (2 microg per 100 g, weekly) or vehicle and daily injections of prolactin (0.25 mg/100 g) or saline (0.05 ml) for 30 days. Other groups of mice received injections of estradiol or vehicle and injections of saline, and were allowed to drink bromocriptine (25 mg/l), metoclopramide (25 mg/l), or only tap water for 30 days. Prolactin administration results in a decrease in the incidence of abnormal glands with abnormal epithelium, the incidence of atypical hyperplasia, uterine weight, proliferation (the number of mitotic and bromodeoxyuridine-labeled cells) and the levels of estrogen receptor alpha, but causes an increase in the level of beta-catenin in uterine tissues of estrogen-treated mice. The effect of metoclopramide, which increases prolactin secretion, is principally similar to prolactin, but much less expressed. Bromocriptine, which reduces prolactin levels, increases uterine weight, proliferation, the levels of estrogen receptor-alpha, the incidence of abnormal glands with abnormal epithelium, the incidence of complex and atypical hyperplasia, and decreases the level of beta-catenin in uterine structures of estrogen-treated mice. In the absence of estradiol, none of the treatments used had any effect on the parameters tested. Thus, prolactin or metoclopramide produce antiestrogenic effects in the uterus of mice and prevent the formation of atypical hyperplasia which has an unfavorable prognosis, but bromocriptine has the opposite effect. Estrogen receptor-alpha and beta-catenin were associated with the actions of prolactin, metoclopramide and bromocriptine on estrogen dependent processes in the uterus. PMID- 11786375 TI - The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function. AB - Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses of glucocorticoids on postnatal hypothalamic-pituitary adrenal (HPA) function. To determine the effects of maternal or fetal betamethasone administration (0.5 mg/kg maternal or estimated fetal weight) on postnatal HPA function at 6 months and 1 year postnatal age, pregnant ewes were randomized into the following treatment groups: no treatment (n=6); maternal saline (n=6); single maternal betamethasone (M1) (n=6); repeated maternal betamethasone (M4) (n=6); fetal saline (n=5); single fetal betamethasone (n=6) and repeated fetal betamethasone (F4) (n=6). Single injections were given at 104 days of gestation and repeated injections at 104, 111, 118 and 125 days. Lambs were born spontaneously and the ACTH and cortisol responses to i.v. corticotropin releasing hormone (CRH) (0.5 microg/kg) plus arginine vasopressin (AVP) (0.1 microg/kg) were measured at 6 months and 1 year postnatally. At 6 months postnatal age, neither maternal nor fetal prenatal betamethasone administration altered significantly the ACTH and cortisol responses to CRH+AVP. However, in animals at 1 year postnatal age, a previous single injection of betamethasone to the mother (M1) resulted in significantly elevated basal and stimulated cortisol levels (P<0.05), without significant change in the ACTH response. In contrast, betamethasone administration to the fetus resulted in significantly attenuated ACTH responses to CRH+AVP at 1 year compared with control animals (P<0.05), but these were not associated with any significant changes in basal or stimulated cortisol levels. All control animals exhibited a significant increase in peak ACTH responses to CRH+AVP between 6 months and 1 year postnatal age (P<0.05). After prenatal betamethasone (F4, M4) the difference in peak ACTH response between animals at 6 months and 1 year postnatal age was abolished. We conclude that in sheep between 6 months and 1 year postnatal age, HPA function undergoes developmental changes that are influenced by prenatal glucocorticoid exposure. Furthermore, the effects of glucocorticoid on postnatal HPA responses may vary according to the time in gestation that the steroid was administered, and whether it was given directly into the fetal or maternal compartment. PMID- 11786376 TI - Dysregulation of IGF-I signaling in uterine leiomyoma. AB - IGF-I expression has been observed in human uterine leiomyomas. To examine whether autocrine IGF-I signaling plays a role in the growth of these tumors, we used an animal model of uterine leiomyoma (the Eker rat) to investigate regulation of IGF-I and the IGF-I receptor (IGF-IR) expression in tumors and normal myometrium. During the normal estrous cycle, myometrial IGF-I expression peaked on the day of proestrus when the rate of proliferation in this tissue is greatest. In leiomyomas, the expression of IGF-I was increased 7.5-fold compared with the age-matched normal tissue. The level of IGF-IR mRNA in both tumor and non-tumor tissues was found to inversely correlate with that of IGF-I. Changes observed in IGF-I signaling components correlated with the activation state of the signal-transducing protein insulin receptor substrate-1 (IRS-1). During diestrus and proestrus when IGF-I levels were increasing, tyrosine phosphorylation of IRS-1 was increased up to 5.7-fold in the normal myometrium relative to estrus, when IGF-I levels were the lowest. Additionally, IRS-1 phosphorylation was 4-fold greater in leiomyomas relative to age-matched normal myometrium. Autocrine stimulation of the IGF-IR may, therefore, play a role in regulating the normal growth of the myometrium, and dysregulation of IGF-I signaling could contribute to the neoplastic growth of uterine leiomyomas. PMID- 11786377 TI - Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production. AB - We have previously demonstrated that the release of arachidonic acid (AA) from human chorionic gonadotropin (hCG)-stimulated Leydig cells occurs in a dose- and time-dependent manner. In addition, the amount of AA released was dependent on the hormone-receptor interaction and the concentration of LH-hCG binding sites on the cell surface. The present study was conducted to evaluate the involvement of phospholipase A(2) (PLA(2)) and G proteins in AA release from hormonally stimulated rat Leydig cells, and the possible role of this fatty acid in cAMP production. Cells were first prelabelled with [(14)C]AA to incorporate the fatty acid into cell phospholipids, and then treated in different ways to evaluate AA release. hCG (25 mIU) increased the release of AA to 180+/-12% when compared with AA released from control cells, arbitrarily set as 100%. Mepacrine and parabromophenacyl bromide (pBpB), two PLA(2) inhibitors, decreased the hormone stimulated AA release to 85+/-9 and 70+/-24% respectively. Conversely, melittin, a PLA(2) stimulator, increased the release of AA up to 200% over control. The inhibitory effect of mepacrine on the release of AA was evident in hCG-treated Leydig cells, but not in the melittin-treated cells. To determine if the release of AA was also mediated through a G protein, cells were first permeabilized and subsequently treated with pertussis toxin or GTPgammaS, a non-hydrolyzable analog of GTP. Results demonstrate that GTPgammaS was able to induce a similar level of the release of AA as hCG. In addition, pertussis toxin completely abolished the stimulatory effect of hCG on the release of AA, indicating that a member of the G(i) family was involved in the hCG-dependent release of AA. Cells treated with PLA(2) inhibitors did not modify cAMP production, but exogenously added AA significantly reduced cAMP production from hCG-treated Leydig cells, in a manner dependent on the concentration of AA and hCG. Results presented here suggest an involvement of PLA(2) and G proteins in the release of AA from hCG-stimulated Leydig cells, and under particular conditions, regulation of cAMP production by this fatty acid in these cells. PMID- 11786378 TI - The GnRH system in the European sea bass (Dicentrarchus labrax). AB - The cDNA sequences encoding three GnRH forms, sea bream GnRH (sbGnRH), salmon GnRH (sGnRH) and chicken GnRH II (cGnRH II), were cloned from the brain of European sea bass, Dicentrarchus labrax. Comparison of their deduced amino acid sequences to the same forms in the gilthead sea bream, Sparus aurata, and striped bass, Morone saxatilis, revealed high homology of the prepro-cGnRH II (94% and 98% respectively), and prepro-sGnRH (92% to both species). The sbGnRH exhibited dissimilar identities, with high homology to the striped bass (93%), and lower homology (59%) to the gilthead sea bream. Two transcript types were identified for the GnRH-associated peptide (GAP)-sGnRH as well as for the GAP-cGnRH II, which suggests a possible alternative splicing followed by the addition of an early stop codon. In order to obtain antibodies specific for the three GnRH precursors, recombinant GAP proteins were produced. The differential expression of the three GnRHs previously reported in the brain by means of in situ hybridization, using riboprobes corresponding to the GAP-coding regions, was fully confirmed by immunocytochemistry using antibodies raised against the recombinant GAP proteins, indicating that the transcripts are translated into functional proteins. Moreover, this approach allowed us to follow, for the first time, the specific projections of the different cell groups: sGAP fibers are distributed mainly in the forebrain with few projections reaching the pituitary, sbGAP fibers are mainly present in the preoptic area, mediobasal hypothalamus and predominantly project to the pars distalis of the pituitary, whereas cGnRH II fibers have a widespread distribution primarily in the posterior brain, and do not project to the pituitary. These new tools will be extremely useful to study further the development, regulation and functional significance of three independent GnRH systems in the brain of vertebrate species. PMID- 11786379 TI - Ghrelin: a hypothalamic GH-releasing factor in domestic fowl (Gallus domesticus). AB - Ghrelin, a recently discovered peptide in the mammalian hypothalamus and gastrointestinal tract is thought to be the endogenous ligand for the GH secretagogue (GHS) receptor and it stimulates GH release in rats and humans. The possibility that ghrelin is present in birds was therefore assessed, since a GHS receptor is present in the chicken pituitary gland. Although immunoreactive ghrelin is readily detectable in the rat stomach and ileum, ghrelin immunoreactivity could not be detected in the chicken proventriculus, stomach, ileum or colon, whereas somatostatin immunoreactivity, in contrast and as expected, was readily detectable in the chicken gastrointestinal tract. Ghrelin immunoreactivity was, however, present in the chicken hypothalamus, although not in the arcuate (infundibular) nucleus, as in rats. Discrete parvocellular cells and neuronal fibers with ghrelin immunoreactivity were present in the anterior medial hypothalamus. This immunoreactivity was specific and completely abolished following the preabsorption of the antibody with an excess of human ghrelin. Ghrelin immunoreactivity was also present in clusters of large ovoid magnocellular cells in the nucleus magnocellularis preopticus pars medialis, nucleus magnocellularis preopticus supraopticus and in the chiasmaopticus. Immunoreactivity for ghrelin was restricted to the cytoplasm of the perikarya and their axonal sprouts. Immunoreactivity for ghrelin was not seen in any other hypothalamic nuclei. In a preliminary experiment, circulating GH concentrations in conscious immature chicks were promptly increased following bolus i.v. administration of human ghrelin. The increase in GH concentration (approximately three times that in the controls) was comparable with that induced by the same dose (10 microg/kg) of human GH-releasing hormone, although less than that (approximately sixfold) induced by thyrotropin-releasing hormone. These results demonstrate the presence of a ghrelin-like protein in the chicken hypothalamus and suggest that it participates in the regulation of GH secretion in birds. PMID- 11786380 TI - Impaired insulin signaling in the liver of transgenic rats with low circulating growth hormone levels. AB - GH is known to regulate glucose and lipid metabolism as well as body growth. Controversy exists as to whether GH-deficient adults are indeed insulin sensitive or insulin resistant. In GH-deficient animal models, however, no clear observation indicating insulin resistance has been made, while increased insulin sensitivity has been reported in those animals. We have produced human GH (hGH) transgenic rats characterized by low circulating hGH levels and virtually no endogenous rat GH secretion. Although the body length of the transgenic rat is normal, they develop massive obesity and insulin resistance, indicating that the transgenic rat is a good model for the analysis of insulin resistance under GH deficiency. In this study, we have examined how GH deficiency affects the early steps of insulin signaling in the liver of the transgenic rat. Circulating glucose and insulin concentrations were significantly higher in the transgenic rats than in their littermates. In addition, impaired glucose tolerance was observed in the transgenic rat. The amount of insulin receptor was smaller in the liver of the transgenic rat, resulting in decreased tyrosine phosphorylation in response to insulin stimulation. The amounts of insulin receptor substrate-1 and 2 (IRS-1 and -2) and insulin-stimulated phosphorylation of IRSs were also smaller in the transgenic rat. Despite the decrease in tyrosine phosphorylation levels of IRSs being mild to moderate (45% for IRS-1 and 16% for IRS-2), associated phosphatidylinositol 3-kinase (PI3-kinase) activity was not increased by insulin stimulation at all in the transgenic rat. To elucidate whether this discrepancy resulted from the alteration in binding of the p85 subunit of PI3-kinase to phosphotyrosine residues of the IRSs, we determined the amount of p85 subunit in the immunocomplexes with anti-phosphotyrosine antibody. Insulin did not affect the amount of p85 subunit associated with phosphotyrosine in the transgenic rats, while it significantly increased in the controls, indicating that alteration may have occurred at the sites of phosphorylated tyrosine residues in IRSs. These results suggest that GH deficiency in the transgenic rat leads to impairment in at least the early steps of insulin signaling in the liver with a resultant defect in glucose metabolism. PMID- 11786381 TI - Differential effects of genistein on apoptosis induced by fluoride and pertussis toxin in human and rat pancreatic islets and RINm5F cells. AB - Clonal pancreatic beta-cell lines have been used widely for the study of the factors involved in the regulation of apoptosis but it has not been firmly established that the response of normal islets mirrors that found in transformed beta-cells. In the present work, the role of pertussis toxin (Ptx)-sensitive G proteins in the control of beta-cell apoptosis was studied in isolated rat and human islets of Langerhans and compared with the clonal beta-cell line, RINm5F. Annexin-V and deoxycarboxyfluoroscein diacetate staining was used to identify viable, apoptotic and necrotic cells directly, under fluorescence illumination. Treatment of human and rat islet cells with the G-protein activator fluoride (NaF; 5 mM) caused a marked increase in apoptosis that was further potentiated in islets pretreated with Ptx. The tyrosine kinase inhibitor genistein (100 microM) also increased islet cell apoptosis and the combination of 100 microM genistein and 5 mM NaF did not lead to any diminution of the apoptotic response. This latter effect was quite different from that seen in RINm5F cells where the combination of 100 microM genistein and 5 mM NaF resulted in much less apoptosis than was observed with either agent alone. In islets treated with a lower concentration of genistein (25 microM; that did not, itself, increase cell death), the drug attenuated NaF-induced apoptosis and also blocked the enhancement mediated by Ptx. These results revealed that human (and rat) islets are equipped with a Ptx-sensitive pathway that may be regulated by tyrosine phosphorylation and is anti-apoptotic. However, they also define conditions under which marked differences in response between RINm5F cells and normal islets were observed and they suggest that care should be taken when extrapolating data obtained with clonal cell lines to the situation in normal islet cells. PMID- 11786382 TI - Dual role of the tyrosine kinase GTK and the adaptor protein SHB in beta-cell growth: enhanced beta-cell replication after 60% pancreatectomy and increased sensitivity to streptozotocin. AB - Transgenic CBA mice expressing either the tyrosine kinase GTK (gut tyrosine kinase) or the adaptor protein SHB (Src homology 2 protein of beta-cells) under the control of the rat insulin promoter exhibited an increased beta-cell mass, but also elevated cytokine-induced islet cell death compared with control mice. To further investigate the importance of GTK and SHB for beta-cell death and proliferation, these mice were subjected to a 60% partial pancreatectomy (Px) or a sham-operation and beta-cell replication was determined by autoradiographic detection of [(3)H]thymidine incorporation into islet cells positively stained for insulin. The Px-operated control mice exhibited a moderate and insignificant increase in beta-cell replication 4 days after Px compared with the sham-operated mice (0.27+/-0.08% vs 0.08+/-0.02%). In contrast, the Px-induced beta-cell proliferation was significantly increased in both the GTK- and SHB-transgenic mice compared with the corresponding sham-treated animals (0.64+/-0.12% vs 0.11+/ 0.04% and 0.44+/-0.11% vs 0.09+/-0.04% respectively). This effect was dependent on intracellular signal transduction pathways activated or enhanced by GTK and SHB overexpression, since the proliferation of acinar cells, located in the vicinity of the islets, was equal in the transgenic and control mice. GTK- and SHB-transgenic mice, treated with a sub-diabetogenic dose of the beta-cell toxin streptozotocin (STZ) on day 0 and subjected to a glucose tolerance test on day 3, exhibited an impaired glucose tolerance in comparison with the STZ-treated control mice. Pretreatment with STZ blunted the regenerative response to Px in the transgenic mice. Furthermore, the SHB-transgenic islets were significantly more damaged with respect to beta-cell loss, compared with the islets of the control mice. Previous and present data suggest a dual role of GTK and SHB for beta-cell growth: whereas these proteins increase the beta-cell mass and induce beta-cell proliferation after 60% Px, SHB and GTK also enhance beta-cell death under certain stressful conditions. PMID- 11786383 TI - The HIV protease inhibitor saquinavir impairs lipid metabolism and glucose transport in cultured adipocytes. AB - Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 microg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [(14)C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulin stimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs. PMID- 11786384 TI - Hormonal control of the transcription factor Pax8 and its role in the regulation of thyroglobulin gene expression in thyroid cells. AB - The transcription factor Pax8 plays an important role in the expression of the differentiated phenotype of thyroid follicular cells. It has recently been shown that Pax8 is necessary for thyroglobulin (Tg) gene expression in the fully differentiated rat thyroid cell line PC. We have used the PC model system to investigate the role of Pax8 as a mediator of TSH regulation of Tg gene expression. We have demonstrated that Pax8 expression, as well as Tg expression, is severely reduced in cells grown in the absence of hormones and serum. The re addition of TSH or forskolin to the culture medium is able to restore to wild type levels the expression of both Pax8 and Tg. We have determined that the action of TSH/forskolin on Pax8 is at the transcriptional level. However, the re expression of Pax8 can be observed several hours before that of Tg, suggesting that either another factor is needed or that Pax8 itself must be post translationally modified by a newly synthesized protein to become active. To distinguish between these two possibilities we have stably transfected into PC cells an exogenous Pax8 that is expressed independently of TSH. Our results indicate that in these cells the Tg promoter is still dependent on TSH despite the constitutive presence of Pax8. Furthermore, we also show that in this condition Tg gene transcription requires de novo protein synthesis. In conclusion, TSH regulates the expression of Pax8 at a transcriptional level and also regulates the activity of Pax8 by controlling the expression of one or more as yet unknown factors. PMID- 11786385 TI - Thyroid function and effect of aging in combined hetero/homozygous mice deficient in thyroid hormone receptors alpha and beta genes. AB - The maintenance of thyroid hormone (TH) homeostasis is dependent on the synthesis and secretion of TH regulated by TSH. This is achieved, in turn, by the negative feedback of TH on TSH secretion and synthesis, which requires the interaction with TH receptors (TRs). Derived by alternative splicing of two gene transcription products, three TRs (TRbeta1, TRbeta2 and TRalpha1) interact with TH while another, TRalpha2, binds to DNA but not to TH. In this study we compare the results of thyroid function tests in mice with deletions of the TRalpha and TRbeta genes alone and present novel data on mice that are double homozygous and combined heterozygous. Homozygous deletions of both the TRalpha and TRbeta in the same mouse (TRalphao/o; TRbeta-/-) resulted in serum TSH values only slightly lower than those in athyreotic, Pax8 knockout mice. Whereas the absence of TRalpha alone does not cause resistance to TH, the absence of TRbeta in the presence of TRalpha results in a 205, 169, 544% increase in serum thyroxine (T(4)), triiodothyronine (T(3)) and TSH concentrations respectively. However, in the absence of TRbeta, loss of one TRalpha allele can worsen the resistance to TH with a 243 and 307% increase in T(4) and T(3) respectively. Similarly, while the heterozygous mouse with a single TRbeta allele shows no alteration in thyroid function, the concomitant deletion of TRalpha brings about mild but significant resistance to TH. Furthermore, the severity of the resistance to TH was noted to decrease with age in parallel with the decrease in serum free T(4) values also seen in wild-type mice. These results demonstrate that (1) unliganded TRalpha or TRbeta are not absolutely necessary for the upregulation of TSH; (2) TRbeta but not TRalpha is sufficient for TH-mediated downregulation of TSH; and (3) TRalpha may partially substitute for TRbeta in mediating a partial TH-dependent TSH suppression. PMID- 11786386 TI - Role of Smad1 and Smad4 proteins in the induction of p21WAF1,Cip1 during bone morphogenetic protein-induced growth arrest in human breast cancer cells. AB - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta family of cytokines. The recent observation that BMPs can inhibit breast cancer cell proliferation in vitro suggests that BMPs or the BMP pathway may hold promise as therapeutic targets for the control of breast tumor growth in women. Better to understand the mechanism of BMP-induced growth arrest we examined the effect of BMP-2 and mediators of BMP-2 action on cell proliferation and p21(Cip1) expression in breast cancer cell lines. We show here that BMP-2 potently inhibited the proliferation of breast cancer cell lines that express both Smad1 and Smad4 (CAMA-1, MCF7, MDA-MB-231, T-47D, ZR-75-1), but not that of cells that only express Smad1 (MDA-MB-468). Growth inhibition correlated with up-regulation of p21 mRNA and protein levels. Up-regulation of p21 was resistant to cycloheximide but not to actinomycin D, suggesting that it occurred at the transcriptional level. Using p21 promoter-luciferase reporter constructs we mapped the BMP-responsive region of the p21 promoter to within 211 base pairs of the transcription start site. Induction of p21 promoter activity was rapid and coincided with up-regulation of p21 mRNA and protein levels. p21 promoter activity required both Smad1 and Smad4 and was induced by either BMP-2 or constitutively active type I BMP receptors. Moreover, the C-terminal SSVS region of Smad1 was necessary for activation of the p21 promoter by BMP-2. Taken together, these results indicate that the mechanism of BMP-induced p21 promoter activation involves BMP receptors and BMP Smads. PMID- 11786387 TI - Production and purification of recombinant human inhibin and activin. AB - Inhibin and activin are protein hormones with diverse physiological roles including the regulation of pituitary FSH secretion. Like other members of the transforming growth factor-beta gene family, they undergo processing from larger precursor molecules as well as assembly into functional dimers. Isolation of inhibin and activin from natural sources can only produce limited quantities of bioactive protein. To purify large-scale quantities of recombinant human inhibin and activin, we have utilized stably transfected cell lines in self-contained bioreactors to produce protein. These cells produce approximately 200 microg/ml per day total recombinant human inhibin. Conditioned cell media can be purified through column chromatography resulting in dimeric mature 32-34 kDa inhibin A and 28 kDa activin A. The purified recombinant proteins maintain their biological activity as measured by traditional in vitro assays including the regulation of FSH in rat anterior pituitary cultures and the regulation of promoter activity of the activin-responsive promoter p3TP-luc in tissue culture cells. These proteins will be valuable for future analysis of inhibin and activin function and have been distributed to the US National Hormone and Peptide Program. PMID- 11786388 TI - Biochemical characterization and purification of a binding protein for 24,25 dihydroxyvitamin D3 from chick intestine. AB - An earlier study revealed that 24R,25-dihydroxyvitamin D(3) (24R,25(OH)(2)D(3)) inhibits the rapid actions of 1,25(OH)(2)D(3) on stimulation of calcium transport in perfused duodena, as well as activation of protein kinases C and A. In the present work, a specific binding protein (24,25-BP) has been identified and partially characterized. Percoll-gradient resolution of differential centrifugation fractions from mucosal homogenates revealed the highest levels of specific [(3)H]24R,25(OH)(2)D(3) binding to be in lysosomes (approximately eight to tenfold greater than in basal lateral membrane fractions). Incubation of isolated enterocytes with 6.5 nM [(3)H]24R,25(OH)(2)D(3) for 10 s also demonstrated targeting of the steroid to lysosomal fractions. Using freshly isolated lysosomal fractions, time course studies indicated maximal specific binding after a 2-h incubation on ice. Western analyses revealed that the serum transport protein, DBP (vitamin D binding protein), was absent from both lysosomal and basal lateral membrane fractions. Protein dependence studies demonstrated linear binding between 0.05 and 0.155 mg of lysosomal protein. Saturation analyses yielded K(d)=7.4+/- 1.8 nM, B(max)=142+/-16 fmol/mg protein for lysosomes, and K(d)=8.5 nM, B(max)=149+/-25 fmol/mg protein for basal lateral membranes. Hill analyses of lysosomal binding yielded a Hill coefficient of 0.57+/-0.11, indicative of negative cooperativity. Studies with lysosomal proteins revealed a 81%+/-7% competition of 24S,25(OH)(2)D(3) with [(3)H]24R,25(OH)(2)D(3) for binding (P>0.05, relative to competition with 24R,25(OH)(2)D(3)), while 25(OH)D(3) and 1,25(OH)(2)D(3) yielded 53%+/-13% and 39%+/-11% competition respectively (each, P<0.05, relative to competition with 24R,25(OH)(2)D(3)). The apparent affinity of 24S,25(OH)(2)D(3) for 24,25-BP led to testing of the metabolites effectiveness in the perfused duodenal loop system. Vascular perfusion with 130 pM 1,25(OH)(2)D(3) stimulated (45)Ca transport to 2.5 fold above control levels after 40 min, while simultaneous perfusion with 6.5 nM 24S,25(OH)(2)D(3) and 130 pM 1,25(OH)(2)D(3) abolished the stimulatory activity completely. Purification of the 24,25-BP by chromatography revealed a single protein band upon SDS-PAGE and silver staining of 66 kDa. The combined results suggest that 24R,25(OH)(2)D(3) may mediate its hormonal activities through a specific binding protein. PMID- 11786389 TI - Glucocorticoid-induced glucose release is abolished in trout hepatocytes with elevated hsp70 content. AB - The metabolic potential of cells with elevated heat shock protein 70 (hsp70) content was examined by measuring unstimulated and glucocorticoid-stimulated glucose release in trout hepatocytes maintained in primary culture. Exposure of hepatocytes to either heat shock (HS;+15 degrees C) or sodium arsenite (50 microM) did not affect cell viability, but resulted in significantly higher hsp70 levels over a 24 h recovery period. Hsp70 accumulation had no significant impact on unstimulated glucose release, but completely abolished cortisol-induced glucose release in trout hepatocytes. This lack of glucocorticoid responsiveness corresponded with lower glucocorticoid receptor protein levels. Together, our results suggest that stressor-induced hsp70 accumulation, while important for maintaining cellular homeostasis, may impair metabolic adjustments to subsequent stressors in animals, especially those that are glucocorticoid-dependent. PMID- 11786391 TI - Focusing on the glomerular slit diaphragm: podocin enters the picture. PMID- 11786392 TI - Protein S100A4: too long overlooked by pathologists? PMID- 11786393 TI - The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. AB - Gastrointestinal stromal (pacemaker cell) tumors (GIST/GIPACTs) are frequently associated with activating KIT mutations, primarily of exon 11 and rarely of exons 9 and 13, as well as certain chromosome rearrangements. Reports regarding the frequency and prognostic significance of KIT mutations are conflicting and few cases have been completely sequenced. Furthermore, there are few detailed analyses of chromosome alterations in GIST/GIPACTs. In a detailed analysis of 14 GIST/GIPACTs from 12 patients, we found a wider spectrum of KIT mutations than previously reported, including 11 different in-frame mutations involving exons 11, 14, and 15. No mutations were detected in four malignant tumors. The shorter (GNNK-) KIT isoform was preferentially expressed. Cytogenetic and spectral karyotype analyses of 10 tumors revealed clonal abnormalities in eight tumors; the most common were terminal 1p deletions and losses of chromosomes 14 and/or 22. Neither KIT mutation status nor chromosome aberrations correlated with tumor phenotype or clinical behavior in our series. Collectively, these findings indicate that the role of KIT mutations and chromosomal rearrangements in the pathogenesis of GIST/GIPACTs are more complex than previously recognized. PMID- 11786394 TI - Human herpesvirus-8-transformed endothelial cells have functionally activated vascular endothelial growth factor/vascular endothelial growth factor receptor. AB - Kaposi's sarcoma is a vascular tumor commonly associated with human immunodeficiency virus (HIV)-1 and human herpesvirus (HHV-8) also known as Kaposi's sarcoma-associated herpesvirus. The principal features of this tumor are abnormal proliferation of vascular structures lined with spindle-shaped endothelial cells. HHV-8 may transform a subpopulation of endothelial cells in vitro via viral and cellular gene expression. We hypothesized that among the cellular genes, vascular endothelial growth factors (VEGFs) and their cognate receptors may be involved in viral-mediated transformation. We have shown that HHV-8-transformed endothelial cells (EC-HHV-8) express higher levels of VEGF, VEGF-C, VEGF-D, and PlGF in addition to VEGF receptors-1, -2, and -3. Furthermore, antibodies to VEGF receptor-2 inhibited cell proliferation and viability. Similarly, inhibition of VEGF gene expression with antisense oligonucleotides inhibited EC-HHV-8 cell proliferation/viability. The growth and viability of primary endothelial cells and a fibroblast cell line however were unaffected by either the VEGF receptor-2 antibody or the VEGF antisense oligodeoxynucleotides. VEGF and VEGF receptors are thus induced in EC-HHV-8 and participate in the transformation. Inhibitors of VEGF may thus modulate the disease process during development and progression. PMID- 11786395 TI - Liver repopulation by Bcl-x(L) transgenic hepatocytes. AB - Liver repopulation could constitute a potential therapeutic alternative to liver transplantation in the future. Therefore, the development of liver repopulation strategies is of major interest. We have previously reported that Bcl-2 expressing hepatocytes are resistant to Fas-mediated apoptosis and that these hepatocytes, when transplanted into the spleen, are able to repopulate the liver of normal mice submitted to Fas-mediated apoptosis. We now show that Bcl-x(L) overexpressing hepatocytes are able to repopulate up to 10% of a normal mouse liver treated with successive injections of anti-Fas antibody. We show that a twofold overexpression of Bcl-x(L) is sufficient to confer a selective advantage to hepatocytes submitted to anti-Fas antibody. Moreover, repopulation percentages obtained here were comparable to those obtained when Bcl-2 hepatocytes were transplanted, suggesting that both proteins are equivalent in conferring a selective advantage to hepatocytes submitted to anti-Fas antibody. PMID- 11786396 TI - Characterization of prostate cell types by CD cell surface molecules. AB - A set of monoclonal antibodies raised against lymphocyte cell surface molecules, the cluster designation (CD) antigens, was used to distinguish the constituent cell types of the prostate. The luminal secretory epithelial, basal epithelial, fibromuscular stromal, nerve sheath, and endothelial cells express distinctive complements of cell surface molecules that were identified by immunohistochemistry using 152 commercially available antibodies. Many of the CD antibodies stained lymphocyte populations in the prostate. These lymphocyte populations were grouped into abundance classes of rare, moderate, and high. Some of these molecules are expressed by multiple cell types, both parenchymal and lymphoid; others are expressed by only one cell type. Distinctive patterns of CD expression, which are most similar to the expression pattern of prostate luminal cells, also characterize a small series of Gleason score 6 prostate cancers. The cell-type specificity of CD molecules increases the prospect of isolating specific cell populations, using such techniques as laser capture microdissection and flow cytometry, for cell-specific molecular studies. PMID- 11786397 TI - Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. AB - Using the National Center for Biotechnology Information Serial Analysis of Gene Expression database, we found that S100A4, a calcium-binding protein previously implicated in metastasis, was expressed in five of seven pancreatic carcinoma libraries but not in the two normal pancreatic duct libraries. We confirmed the overexpression of S100A4 using reverse transcriptase-polymerase chain reaction, which demonstrated that 18 of 19 (95%) pancreatic carcinoma cell lines expressed S100A4. Using immunohistochemistry, we found that 57 of 61 invasive pancreatic carcinomas (93%), 3 of 18 high-grade pancreatic intraepithelial neoplasia lesions (17%), and 0 of the 69 low-grade pancreatic intraepithelial neoplasia lesions expressed S100A4 protein, whereas normal pancreatic tissue and tissue affected by chronic pancreatitis did not label. Expression of S100A4 was associated with poor differentiation of the pancreatic adenocarcinomas (P = 0.001). We found that three CpG sites in the first intron of the S100A4 gene were approximately 90% methylated in microdissected normal pancreatic duct cells using bisulfite modified sequencing and in two cell lines and three primary pancreatic carcinomas with a reduced or absent expression of S100A4. In contrast, these CpGs were 100% hypomethylated in 11 of 12 pancreatic cancer cell lines by methylation-specific polymerase chain reaction. The association between the expression of S100A4 and hypomethylation of the first intron of S100A4 was statistically significant (P = 0.002). These data suggest that the majority of pancreatic carcinomas undergo selection for hypomethylation and overexpression of S100A4. Because most pancreatic carcinomas express S100A4, it may be a useful target for early detection strategies. PMID- 11786398 TI - Enrichment, immunomorphological, and genetic characterization of fetal cells circulating in maternal blood. AB - Fetal cells circulating in the peripheral blood of pregnant women are a potential target for noninvasive genetic analyses. They include epithelial (trophoblastic) cells, which are larger than peripheral blood leukocytes. We enriched circulating trophoblastic cells using the isolation by size of epithelial tumor cells (ISET) method. Peripheral blood was obtained at 11 to 12 weeks of pregnancy. Cells isolated by ISET were stained by hematoxylin and eosin or by immunohistochemistry. Large epithelial cells were microdissected and fetal cell identification was obtained by polymerase chain reaction with short tandem repeats and/or Y-specific primers. By analyzing only 2 ml of blood, we found a variable number (n = 1 to 7) of Y-positive cells (overall 15 of 23) in all of the six mothers carrying a male fetus. In contrast, none of the 26 cells isolated from seven mothers carrying a female fetus scored positive. Eleven cells were analyzed by using short tandem repeat-specific markers: six of them showed a fetal profile and five showed a maternal profile consistently with Y-specific results. Only one-fifth of the single cell DNA was used for fetal cell assessment, leaving enough material for further genetic tests. We also show that the ISET approach allows the performance of fluorescence in situ hybridization analyses and the detection of DNA point mutations in single microdissected cells. We conclude that this is a powerful approach to enrich circulating fetal cells and prove their fetal origin, and that it may have implications for noninvasive prenatal diagnosis of genetic disorders. PMID- 11786399 TI - Specific patterns of gene methylation in natural killer cell lymphomas : p73 is consistently involved. AB - Aberrant methylation of promoter CpG regions is a putative mechanism whereby tumor suppressor genes are inactivated. We used a candidate gene approach to investigate the patterns and significance of this epigenetic change in natural killer (NK) cell malignancies. Thirty-three patients were studied for promoter methylation in five putative tumor suppressor genes by methylation-specific polymerase chain reaction (MSP), which has a sensitivity of 10(-3). The p73 gene was methylated in 94% of cases, a frequency that is the highest known for any human malignancy. In the NK cell lymphoma line NK92, p73 was also completely methylated, and the p73 transcript was correspondingly not detectable by quantitative polymerase chain reaction. Treatment of the cell line with 5 azacytidine, a demethylation reagent, led to demethylation of the p73 promoter and reinduction of p73 gene expression. These results suggested that promoter CpG methylation might be an important mechanism in suppressing p73 gene expression in NK cells. Other methylated genes included hMLH1 (63%), p16 (63%), p15 (48%), and RAR beta (47%). Methylation of two or more genes occurred in 88% of cases. With promoter methylation as a molecular marker, MSP identified two cases of occult marrow metastasis. Interestingly, the primary tumor and metastasis showed different methylation patterns, implying that separate clonal evolutions might have occurred at these sites. Furthermore, MSP also identified tumor infiltration in random oropharyngeal biopsies in a case where histological examination could not show evidence of tumor involvement. We conclude that NK cell malignancies show a specific pattern of promoter methylation, with p73 being consistently involved. These results suggest that p73 may be an important target in the neoplastic transformation of NK cells, and the demonstration of its methylation may serve as a potential molecular tool for NK cell lymphoma detection. PMID- 11786401 TI - Single nucleotide polymorphism array analysis of flow-sorted epithelial cells from frozen versus fixed tissues for whole genome analysis of allelic loss in breast cancer. AB - Analysis of allelic loss in archival tumor specimens is constrained by quality and quantity of tissue and by technical limitations on the number of chromosomal sites that can be efficiently evaluated in conventional analyses using polymorphic microsatellite markers. Newly developed array-based assays have the potential to yield genome-wide data from small amounts of tissue but have not been validated for use with routinely processed specimens. We used the Affymetrix HuSNP assay, composed of 1494 single nucleotide polymorphism sites, to compare allelic loss results obtained from both formalin-fixed and frozen breast tissue samples. Tumor cells were separated from normal epithelia and nonepithelial cells by dissection and bivariate cytokeratin/DNA flow sorting; normal breast cells from the same patient served as constitutive normal. Allele results from the HuSNP array averaged 96% reproducibility between duplicates and were concordant between the fixed and frozen normal samples. We also analyzed DNA from the same samples after whole-genome amplification (primer extension preamplification). Although overall signal intensities were lower, the genotype data from the primer extension preamplification material was concordant with genomic DNA data from the same samples. Results from genomic normal tissue DNA averaged informative single nucleotide polymorphism at 379 (25%) loci genome-wide. Although data points were clustered and some segments of chromosomes were not informative, our data indicated that the Affymetrix HuSNP assay could provide an efficient and valid genome-wide analysis of allelic imbalance in routinely processed and whole genome amplified pathology specimens. PMID- 11786400 TI - CD40-CD40 ligand disruption does not prevent hyperoxia-induced injury. AB - Recent studies suggest that apoptosis plays a role in oxygen-induced injury, although the activation pathways and the executioner proteases that lead to cleavage of lung cell proteins and DNA, are not yet identified. We explored previously the tumor necrosis factor/tumor necrosis factor receptor and the Fas/FasL, belonging to the intrinsic pathway, and could not demonstrate any protective effect by interfering with these cell receptors. Lately, it has been shown that interacting with the CD40 system, also known to promote cell death, by administering anti-CD40 ligand (L) antibody was beneficial in several diseases and, in particular, in hyperoxia-induced injury. Using CD40- and CD40L-deficient mice (-/-) as well as administering anti-CD40L antibody, we examined the extent of lung injury in oxygen-breathing mice by several ways (lung weight, histology, inflammatory mediators, and DNA ladder) as well as the mortality. The development of lung injury was similar in wild-type, CD40-/-, CD40L-/-, or in wild-type mice treated with anti-CD40L antibody. Apoptosis was present in all conditions at 72 hours of oxygen exposure. These results show that oxygen-induced injury does not require CD40-CD40L interaction and that apoptosis of lung cells does not involve this pathway. PMID- 11786402 TI - cDNA array hybridization after laser-assisted microdissection from nonneoplastic tissue. AB - Differential gene expression can be investigated effectively by cDNA arrays. Because tissue homogenates result inevitably in an average expression of a bulk of different cells, we aimed to combine mRNA profiling with cell-type-specific microdissection. Using a polymerase chain reaction (PCR)-based preamplification technique, the expression profile was shown to be preserved. We modified the existing protocol enabling to apply the total amount of extracted RNA from microdissected cells. A mean amplification factor of nearly 1000 allowed to reduce the demand of initial RNA to approximately 10 ng. This technique was used to investigate intrapulmonary arteries from mouse lungs ( approximately 500 cell equivalents). Using filters with 1176 spots, three independent experiments showed a high consistency of expression for the preamplified cDNAs. These profiles differed primarily from those of total lung homogenates. Additionally, in experimental hypoxia-induced pulmonary hypertension, amplified cDNA from intrapulmonary vessels of these lungs was compared to cDNA from vessels dissected from normoxic lungs. Validation by an alternative method was obtained by linking microdissection with real-time polymerase chain reaction (PCR). As suggested by the array data, nine selected genes with different factors of up-regulation were fully confirmed by the PCR technique. Thus, a rapid protocol is presented combining microdissection and array profiling that demands low quantities of initial RNA to assess reliably cell-type-specific gene regulation even within nonneoplastic complex tissues. PMID- 11786403 TI - Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion. AB - The dramatic opportunities presented by comprehensive gene profiling technologies are curbed by the problem of segregating these large amounts of gene expression data into meaningful categories for study. This is particularly evident in infiltrating carcinomas of the pancreas, in which global gene expression data primarily mirrors the prominent desmoplastic response to the infiltrating neoplasm. In an effort to better characterize the gene expression of invasive pancreatic cancers and their associated desmoplastic response, we performed in situ hybridization on pancreatic cancer tissues to characterize the expression of 12 genes identified by serial analysis of gene expression as highly expressed in invasive pancreatic cancer tissues but not in pancreatic cancer cell lines. In situ hybridization demonstrated that eight genes were expressed within the stromal and/or angioendothelial cells of the desmoplastic response to the invasive tumor, and four of these genes were specifically expressed by the stromal cells immediately adjacent to the invasive neoplastic epithelium, suggesting regional differences in gene expression within the host desmoplastic response. In contrast, four genes were specifically expressed by the invasive neoplastic epithelium, indicating important differences between in vivo and in vitro gene expression of human epithelial neoplasms. We have identified a highly organized structure of gene expression within the host stromal response to invasive pancreatic cancer that may reflect tumor-host communication and serve as a target for therapeutic intervention. PMID- 11786404 TI - CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. AB - A pathological hallmark of Alzheimer's disease is the senile plaque, composed of beta-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to beta-amyloid fibrils and oxidized low-density lipoprotein (oxLDL) coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H(2)O(2) secretion by macrophages adherent to oxLDL coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H(2)O(2) by microglia interacting with fibrillar beta amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar beta-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar beta-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H(2)O(2) production by N9 microglia and human macrophages adherent to fibrillar beta-amyloid by approximately 50%. Our data identify a role for CD36 in fibrillar beta-amyloid-induced H(2)O(2) production by microglia, and imply that CD36 can mediate binding to fibrillar beta-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar beta-amyloid. PMID- 11786405 TI - Anti-CD3/anti-epidermal growth factor receptor-bispecific antibody retargeting of lymphocytes against human neoplastic keratinocytes in an autologous organotypic culture model. AB - Local cellular immune defects have been described in several tumors including human papillomavirus (HPV)-associated cervical cancer. This observation suggests the potential therapeutic benefit of immune manipulations that restore cellular immunity. Here, we evaluated the ability of bispecific monoclonal antibodies (bimAbs) to redirect T cells against keratinocytes transformed in vitro by HPV in an autologous three-dimensional culture model (organotypic cultures). The epidermal growth factor receptor (EGFR) was chosen as target for an anti-CD3/anti EGFR bimAb because it is overexpressed in many malignant epithelial lesions and only weakly expressed in the basal layers of normal squamous epithelium. Interestingly, in organotypic cultures, the pattern of expression of EGFR was similar to that observed in vivo. The ability of T cells retargeted by CD3/EGFR bimAb to lyse HPV-transformed cell lines was confirmed in monolayer cultures. In autologous organotypic cultures, an increase in apoptotic HPV(+) keratinocytes and a significant decrease in the thickness of HPV(+) organotypic cultures were observed when activated lymphocytes and bimAbs were added to the cultures, whereas organotypic cultures of normal keratinocytes were not significantly affected. These data were similar to those obtained in the allogeneic model. These results suggest the potential usefulness of CD3-EGFR bimAb-retargeted lymphocytes in immunotherapeutic protocols for malignant epithelial lesions. PMID- 11786406 TI - Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. AB - The role of the tumor suppressor p53 as a key regulator of inflammation was examined in murine collagen-induced arthritis (CIA), a model of rheumatoid arthritis. Wild-type DBA/1 mice develop progressive arthritis in this model, in which p53 expression and apoptosis are evident in the synovial cells. In contrast, the joints of p53(-/-) DBA/1 animals with CIA showed increased severity of arthritis using clinical and histological scoring methods with almost no apoptosis. Consistent with this, collagenase-3 expression and cytokine production (interleukin-1 and interleukin-6) in the joints of p53(-/-) mice with CIA were significantly greater than in wild-type mice. Anti-collagen antibody titers, however, were not different. Therefore, p53 expression occurs during inflammation and acts to suppress local inflammatory responses. Because mutations in p53 have been described in the synovial membrane of rheumatoid arthritis patients, the loss of p53 function in synoviocytes or other cells in the joint because of dominant-negative mutations might contribute to invasion and destruction of the joint in this disease. PMID- 11786407 TI - Podocin localizes in the kidney to the slit diaphragm area. AB - We recently cloned a novel gene, NPHS2, involved in autosomal recessive steroid resistant nephrotic syndrome. This gene encodes a novel podocyte protein, podocin. Given its similarity with the stomatin family proteins, podocin is predicted to be an integral membrane protein with a single membrane domain forming a hairpin-like structure placing both N- and C-termini in the cytosol. Here, we show by in situ hybridization, that during development, the NPHS2 transcript is first expressed in mesonephric podocytes from the S-shaped body and, later, in the metanephric kidney, in the future podocytes at the late S shaped body stage. In the mature kidney, NPHS2 is exclusively expressed in the podocytes of mature glomeruli. We generated rabbit polyclonal antibodies against fusion proteins derived from the N- and the C-terminal regions of podocin which detected a single band of 49-kd in transfected HEK293 cell lysates by immunoprecipitation and Western blotting. By immunohistology, podocin was detected in podocytes from the early capillary loop stage in the developing nephrons, and at the basal pole, along the GBM, in mature glomeruli. By electron microscopy, we demonstrate that podocin is facing the slit diaphragm with its two ends in the cytoplasm of the foot processes, in agreement with its predicted structure. Our results suggest that podocin could serve to anchor directly or indirectly components of the slit diaphragm to the cytoskeleton. PMID- 11786408 TI - Induction and immunohistology of autoimmune ovarian disease in cynomolgus macaques (Macaca fascicularis). AB - Autoimmune ovarian disease (AOD) is a probable cause of human premature ovarian failure, and a potential complication of contraceptive vaccines based on ovarian antigens. The diagnosis depends on detection of noninfectious ovarian inflammation (oophoritis) and serum antibody to ovarian and placental antigens. Mechanisms underlying AOD have been investigated in mice but not in primates. Herein, we report induction of AOD in primates, and compare the immunopathology between monkey and murine AOD. Four cynomolgus macaques immunized with monkey or human zona pellucida 3 peptide (pZP3) in adjuvant, developed T-cell responses to the immunizing peptide and produced antibody that bound to native zona pellucida in vivo. Immunostaining of ovaries from pZP3-immunized macaques showed numerous clusters of T cells co-localized with major histocompatibility complex II positive macrophages in the ovarian interstitium. Such foci were not detected in untreated or adjuvant-treated control monkeys. This finding is comparable to murine pZP3-induced AOD. However, unlike murine AOD in which numerous granulomatous lesions are detected, severe granulomatous inflammation was detected in only one of three monkeys with abnormal immunohistology. Similar to mice with pZP3-induced AOD, the immunized monkeys retained normal ovarian function. The results are discussed in the context of complications of ZP-based human immunocontraceptive vaccines and case reports of human autoimmune oophoritis. PMID- 11786409 TI - Lymphoid follicles are generated in high-grade cervical dysplasia and have differing characteristics depending on HIV status. AB - The exact role of the mucosal immune response in the pathogenesis of human papillomavirus (HPV)-related premalignant and malignant diseases of the genital tract is poorly understood. We used immunohistochemical analysis to characterize immune cells in normal cervix (N = 21), HIV-negative high-grade dysplasia (N = 21), and HIV-positive high-grade dysplasia (N = 30). Classical germinal centers were present in 4.7% of normal cervix, 33% of high-grade lesions from HIV negative women, and 3.3% of high-grade lesions from HIV-positive women (P = 0.003). HPV16 E7 antigen was detected in a subset of germinal centers, indicating that the secondary immune response was directed in part against HPV. Lymphoid follicles were present in 9.5% of normal cervix, 57% of HIV-negative high-grade dysplasia, and 50% of HIV-positive high-grade dysplasia (P = 0.001 normal versus high-grade). A novel type of lymphoid aggregate, consisting predominantly of CD8(+) T cells, was detected in 4.8% of normal cervix, 0% of HIV-negative high grade dysplasia, and 40% of HIV-positive high-grade dysplasia (P < 0.001). The recurrence rate of high-grade dysplasia within one year was significantly higher in women with such CD8(+) T cell-dominant aggregates (P = 0.02). In summary, the types of lymphoid follicle in lesions from HIV-positive women were significantly different from those from HIV-negative women, and these differences are associated with the worse clinical outcome in HIV-positive women. PMID- 11786410 TI - Commensal-associated molecular patterns induce selective toll-like receptor trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. AB - Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand specific dynamic regulation in the model human intestinal epithelial cell line T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors. PMID- 11786411 TI - Clinical significance of molecular expression profiles of Hurthle cell tumors of the thyroid gland analyzed via tissue microarrays. AB - Hurthle cell tumors are rare thyroid neoplasms for which disease biology is poorly understood and diagnosis of carcinoma can be challenging. The aim of the study was to characterize molecular expression profiles of Hurthle cell tumors and to determine the clinical significance of identified phenotypes. Paraffin embedded tissue cores of normal thyroid (n = 18), and histopathologically well defined Hurthle cell adenomas (n = 27), Hurthle cell tumors of unknown malignant behavior (n = 7), and minimally (n = 14) and widely (n = 21) invasive Hurthle cell carcinomas were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, and Ki-67 were detected by immunohistochemistry and correlated with clinicopathological data and patient outcome using standard statistical methodology. Median follow-up time was 8 years. High Ki-67 proliferative index was evident only in the clinically aggressive widely invasive Hurthle cell carcinomas and was associated with significantly reduced relapse-free (P = 0.001) and disease-specific (P < 0.001) survival. The molecular phenotype of Hurthle cell tumors, independent of histopathological subtype diagnosis, was characterized by p53(-), mdm-2(+), p21(+/-), cyclin D1(-), and Bcl-2(+/-). Normal thyroid tissue demonstrated a p53( ), mdm-2(-), p21(-), cyclin D1(-), and Bcl-2(+) phenotype. The Bcl-2(+) phenotype was associated with improved relapse-free survival (P = 0.04) and disease specific survival (P = 0.01) in widely invasive carcinomas and the Ki-67(+)/Bcl 2(-) phenotype was associated with the diagnosis of widely invasive Hurthle cell carcinoma (P < 0.001). This study demonstrates that tissue microarray-based profiling allows identification of molecular markers that are associated with patient prognosis. High Ki-67 proliferative index was associated with adverse outcome in Hurthle cell neoplasms. Together with down-regulation of Bcl-2, high Ki-67 proliferative index may be useful for diagnosing widely invasive Hurthle cell carcinomas. Molecular alterations in the p53 pathway play a role in Hurthle cell tumorigenesis, but other unidentified molecular changes seem to be required to induce the malignant phenotype. PMID- 11786412 TI - Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas. AB - Binding of fibroblast growth factors (FGFs) to their tyrosine kinase-signaling receptors (FGFRs) requires heparan sulfate (HS). HS proteoglycans (HSPGs) determine mitogenic responses of breast carcinoma cells to FGF-2 in vitro. For this study, we examined the role of HSPGs as modulators of FGF-2 binding to FGFR 1 in situ and in vitro. During stepwise reconstitution of the FGF-2/HSPG/FGFR-1 complex in situ, we identified an elevated ability of breast carcinoma cell HSPGs to promote receptor complex formation compared to normal breast epithelium. HSPGs isolated from the MCF-7 breast-carcinoma cell line were then fractionated according to their ability to assemble the FGF-2 receptor complex. All MCF-7 HSPGs are decorated with HS chains similarly capable of promoting FGF-2 receptor complex formation. In this in vitro model, syndecan-1 and syndecan-4 are the cell surface HSPGs contributing most to the complex formation. Relative expression levels of these syndecans in human breast carcinoma tissues correlate well with receptor complex formation in situ, indicating that in breast carcinomas, core protein levels determine FGF-2 receptor complex formation. However, variances in syndecan expression levels do not explain the difference in FGF-2 receptor complex formation between normal and malignant epithelial cells, suggesting that alterations in HS structure occur during malignant transformation. PMID- 11786413 TI - The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. AB - Angiogenesis is a complex process, involving functional cooperativity between cytokines and endothelial cell (EC) surface integrins. In this study, we investigated the mechanisms through which the alpha(1)beta(1) and alpha(2)beta(1) integrins support angiogenesis driven by vascular endothelial growth factor (VEGF). Dermal microvascular EC attachment through either alpha(1)beta(1) or alpha(2)beta(1) supported robust VEGF activation of the Erk1/Erk2 (p44/42) mitogen-activated protein kinase signal transduction pathway that drives EC proliferation. Haptotactic EC migration toward collagen I was dependent on alpha(1)beta(1) and alpha(2)beta(1) as was VEGF-stimulated chemotaxis of ECs in a uniform collagen matrix. Consistent with the functions of alpha(1)beta(1) and alpha(2)beta(1) in supporting signal transduction and EC migration, antibody antagonism of either integrin resulted in potent inhibition of VEGF-driven angiogenesis in mouse skin. Moreover, combined antagonism of alpha(1)beta(1) and alpha(2)beta(1) substantially reduced tumor growth and angiogenesis of human squamous cell carcinoma xenografts. Collectively, these studies identify critical collaborative functions for the alpha(1)beta(1) and alpha(2)beta(1) integrins in supporting VEGF signal transduction, EC migration, and tumor angiogenesis. PMID- 11786414 TI - Nuclear factor-kappa B activation in human testicular apoptosis. AB - Apoptotic cell death plays an important role in limiting testicular germ cell population during spermatogenesis and its dysregulation has been shown to be associated with male infertility. The growing evidence on the role of the transcription factor nuclear factor (NF)-kappa B in controlling apoptosis prompted us to investigate NF-kappa B activity in the normal human testis and its role in testis tissue undergoing excessive apoptosis in vitro. In electrophoretic mobility shift assays, low-level constitutive NF-kappa B DNA-binding activity was found and, by immunostaining of the RelA and p50 NF-kappa B subunits, was localized to Sertoli cell nuclei. During in vitro-induced testicular apoptosis, the Sertoli cell nuclear NF-kappa B levels and whole seminiferous tubule NF-kappa B DNA-binding activity increased previous detection of germ cells undergoing apoptosis. The anti-inflammatory drug sulfasalazine effectively suppressed stress induced NF-kappa B DNA binding and NF-kappa B-mediated I kappa B alpha gene expression. Importantly, concomitantly with inhibiting NF-kappa B, sulfasalazine blocked germ cell apoptosis. These results suggest that during testicular stress Sertoli cell NF-kappa B proteins exert proapoptotic effects on germ cells, which raises the possibility that pharmacological inhibition of NF-kappa B could be a therapeutic target in transient stress situations involving excessive germ cell death. PMID- 11786415 TI - Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft. AB - Androgen receptor expression was analyzed in the CWR22 human prostate cancer xenograft model to better understand its role in prostate cancer recurrence after castration. In androgen-dependent tumors, 98.5% of tumor cell nuclei expressed androgen receptor with a mean optical density of 0.26 +/- 0.01. On day 2 after castration androgen deprivation decreased immunostained cells to 2% that stained weakly (mean optical density, 0.16 +/- 0.08). Cellular proliferation measured using Ki-67 revealed <1% immunostained cells on day 6. Androgen receptor immunostained cells increased to 63% on day 6 and 84% on day 32 although immunostaining remained weak. Cellular proliferation was undetectable beyond day 6 after castration until multiple foci of 5 to 20 proliferating cells became apparent on day 120. These foci expressed increased levels of prostate-specific antigen, an androgen receptor-regulated gene product. In tumors recurrent 150 days after castration androgen receptor-immunostaining intensity was similar to CWR22 tumors from intact mice although the percentage of cells immunostained was more variable. The appearance of proliferating tumor cells that expressed androgen receptor and prostate-specific antigen 120 days after castration suggests that these cells represent the origin of recurrent tumors. PMID- 11786416 TI - Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits. AB - Elevated plasma lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the mechanism underlying Lp(a) atherogenicity is unclear. Recently, we demonstrated that Lp(a) may potentially be proatherogenic in transgenic rabbits expressing human apolipoprotein(a) [apo(a)]. In this study, we further investigated atherosclerotic lesions of transgenic rabbits by morphometry and immunohistochemistry. On a cholesterol diet, human apo(a) transgenic rabbits had more extensive atherosclerotic lesions of the aorta, carotid artery, iliac artery, and coronary artery than did nontransgenic littermate rabbits as defined by increased intimal lesion area. Enhanced lesion development in transgenic rabbits was characterized by increased accumulation of smooth muscle cells, that was often associated with the Lp(a) deposition. To explore the possibility that Lp(a) may be involved in the smooth-muscle cell phenotypic modulation, we stained the lesions using a panel of monoclonal antibodies against smooth-muscle myosin heavy-chain isoforms (SM1, SM2, and SMemb) and basic transcriptional element binding protein-2 (BTEB2). We found that a large number of smooth muscle cells located in the apo(a)-containing areas of transgenic rabbits were positive for SMemb and BTEB2, suggesting that these smooth muscle cells were either immature or in the state of activation. In addition, transgenic rabbits showed delayed fibrinolytic activity accompanied by increased plasma plasminogen activator inhibitor-1. We conclude that Lp(a) may enhance the lesion development by mediating smooth muscle cell proliferation and dedifferentiation possibly because of impaired fibrinolytic activity. PMID- 11786417 TI - Promigratory effect of plasminogen activator inhibitor-1 on invasive breast cancer cell populations. AB - The urokinase-type plasminogen activator (uPA) system is a dynamic complex in which the membrane receptor uPAR binds uPA that binds the plasminogen activator inhibitor (PAI)-1 localized in the extracellular matrix, resulting in endocytosis of the whole complex by the low-density lipoprotein receptor-related protein (LRP). High expression of PAI-1 is paradoxically associated with marked tumor spreading and poor prognosis. We previously reported a nonproteolytic role of the [uPAR:uPA:PAI-1:LRP] complex operative in cell migration. Here we explored whether matrix PAI-1 could be used as a migration support by human breast cancer cells. We showed that the uPA system and LRP are localized at filopodia of invasive cells, and that formation/internalization of the [uPAR:uPA:PAI-1:LRP] complex is required for attachment and migration of cancer cells on plastic and on a PAI-1 coat. PAI-1 increased both filopodia formation and migration of cancer cells suggesting a chemokine-like activity. Migration velocity, expression of the uPA system, use of the [uPAR:uPA:PAI-1:LRP] complex to migrate, and promigratory effects of PAI-1 paralleled cancer cell invasiveness. Phenotyping and functional analysis of invasive cancer cell subclones indicated that different cell subpopulations may use different strategies to migrate depending on both the environment and their expression of the uPA system, some of them taking advantage of abundant available PAI-1. PMID- 11786418 TI - Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma. AB - The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC), characterized by tall cells bearing an oxyphilic cytoplasm, is more clinically aggressive than conventional PTC. RET tyrosine kinase rearrangements, which represent the most frequent genetic alteration in PTC, lead to the recombination of RET with heterologous genes to generate chimeric RET/PTC oncogenes. RET/PTC1 and RET/PTC3 are the most prevalent variants. We have found RET rearrangements in 35.8% of TCV (14 of 39 cases). Whereas the prevalences of RET/PTC1 and RET/PTC3 were almost equal in classic and follicular PTC, all of the TCV-positive cases expressed the RET/PTC3 rearrangement. These findings prompted us to compare RET/PTC3 and RET/PTC1 in an in vitro thyroid model system. We have expressed the two oncogenes in PC Cl 3 rat thyroid epithelial cells and found that RET/PTC3 is endowed with a strikingly more potent mitogenic effect than RET/PTC1. Mechanistically, this difference correlated with an increased signaling activity of RET/PTC3. In conclusion, we postulate that the correlation between the RET/PTC rearrangement type and the aggressiveness of human PTC is related to the efficiency with which the oncogene subtype delivers mitogenic signals to thyroid cells. PMID- 11786419 TI - p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases. AB - Exposure of cells to stress, particularly oxidative stress, leads to misfolding of proteins and, if they are not refolded or degraded, to cytoplasmic protein aggregates. Protein aggregates are characteristic features of a variety of chronic toxic and degenerative diseases, such as Mallory bodies (MBs) in hepatocytes in alcoholic and non-alcoholic steatohepatitis, neurofibrillary tangles in neurons in Alzheimer's, and Lewy bodies in Parkinson's disease. Using 2D gel electrophoresis and mass spectrometry, we identified p62 as a novel MB component. p62 and cytokeratins (CKs) are major MB constituents; HSP 70, HSP 25, and ubiquitinated CKs are also present. These proteins characterize MBs as a prototype of disease-associated cytoplasmic inclusions generated by stress induced protein misfolding. As revealed by transfection of tissue culture cells overexpressed p62 did not induce aggregation of regular CK filaments but selectively bound to misfolded and ubiquitinated CKs. The general role of p62 in the cellular response to misfolded proteins was substantiated by detection of p62 in other cytoplasmic inclusions, such as neurofibrillary tangles, Lewy bodies, Rosenthal fibers, intracytoplasmic hyaline bodies in hepatocellular carcinoma, and alpha1-antitrypsin aggregates. The presence of p62 along with other stress proteins and ubiquitin in cytoplasmic inclusions indicates deposition as aggregates as a third line of defense against misfolded proteins in addition to refolding and degradation. PMID- 11786420 TI - Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency. AB - Caveolin-3, a muscle specific caveolin-related protein, is the principal structural protein of caveolar membranes. We have recently identified an autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) that is due to caveolin-3 deficiency and caveolin-3 gene mutations. Here, we studied by electron microscopy, including freeze-fracture and lanthanum staining, the distribution of caveolae and the organization of the T-tubule system in caveolin 3 deficient human muscle fibers. We found a severe impairment of caveolae formation at the muscle cell surface, demonstrating that caveolin-3 is essential for the formation and organization of caveolae in muscle fibers. In addition, we also detected a striking disorganization of the T-system openings at the sub sarcolemmal level in LGMD-1C muscle fibers. These observations provide new perspectives in our understanding of the role of caveolin-3 in muscle and of the pathogenesis of muscle weakness in caveolin-3 deficient muscle. PMID- 11786421 TI - Regulation of signal transducer and activator of transcription and suppressor of cytokine-signaling gene expression in the brain of mice with astrocyte-targeted production of interleukin-12 or experimental autoimmune encephalomyelitis. AB - Interleukin (IL)-12 and interferon (IFN)-gamma are implicated in the pathogenesis of immune disorders of the central nervous system (CNS). To define the basis for the actions of these cytokines in the CNS, we examined the temporal and spatial regulation of key signal transducers and activators of transcription (STATs) and suppressors of cytokine signaling (SOCS) in the brain of transgenic mice with astrocyte production of IL-12 or in mice with experimental autoimmune encephalomyelitis (EAE). In healthy mice, with the exception of STAT4 and STAT6, the expression of a number of STAT and SOCS genes was detectable. However, in symptomatic transgenic mice and in EAE significant up-regulation of STAT1, STAT2, STAT3, STAT4, IRF9, and SOCS1 and SOCS3 RNA transcripts was observed. Although the increased expression of STAT1 RNA was widely distributed and included neurons, astrocytes, and microglia, STAT4 and STAT3 and SOCS1 and SOCS3 RNA was primarily restricted to the infiltrating mononuclear cell population. The level and location of the STAT1, STAT3, and STAT4 proteins overlapped with their corresponding RNA and additionally showed nuclear localization indicative of activation of these molecules. Thus, in both the glial fibrillary acidic protein IL-12 mice and in EAE the CNS expression of key STAT and SOCS genes that regulate IL-12 (STAT4) and IFN-gamma (STAT1, SOCS1, and SOCS3) receptor signaling is highly regulated and compartmentalized. We conclude the interaction between these positive and negative signaling circuits and their distinct cellular locations likely play a defining role in coordinating the actions of IL-12 and IFN-gamma during the pathogenesis of type 1 immune responses in the CNS. PMID- 11786422 TI - Neuropilin-1 participates in wound angiogenesis. AB - Angiogenesis, the formation of new capillaries from existing vasculature, plays an essential role in tissue repair. The rapid onset and predominance of proangiogenic factors optimizes healing in damaged tissues. One factor that directly mediates wound vessel angiogenesis is vascular endothelial growth factor (VEGF). Although much is known about the biology of VEGF and its cognate receptors, VEGFR1 and VEGFR2, the role of a recently identified co-receptor for VEGF, neuropilin-1, is not well understood. Using a murine model of dermal wound repair, we found that neuropilin-1 was abundantly expressed on new vasculature in healing wounds. Moreover, mice treated with anti-neuropilin-1 antibodies exhibited a significant decrease in vascular density within these wounds (67% decrease, P = 0.0132). In in vitro assays, VEGF induced formation of endothelial cord-like structures on collagen gel and endothelial cell migration toward VEGF was inhibited by antibodies directed against neuropilin-1. These results provide both in vitro and in vivo evidence for a critical role of neuropilin-1 in wound angiogenesis. PMID- 11786424 TI - Synthetic peptides interacting with the 67-kd laminin receptor can reduce retinal ischemia and inhibit hypoxia-induced retinal neovascularization. AB - The high-affinity 67-kd laminin receptor (67LR) is expressed by proliferating endothelial cells during retinal neovascularization. The role of 67LR has been further examined experimentally by administration of selective 67LR agonists and antagonists in a murine model of proliferative retinopathy. These synthetic 67LR ligands have been previously shown to stimulate or inhibit endothelial cell motility in vitro without any direct effect on proliferation. In the present study, a fluorescently labeled 67LR antagonist (EGF(33-42)) was injected intraperitoneally into mice and its distribution in the retina was assessed by confocal scanning laser microscopy. Within 2 hours this peptide was localized to the retinal vasculature, including preretinal neovascular complexes, and a significant amount had crossed the blood retinal barrier. For up to 24 hours postinjection, the peptide was still present in the retinal vascular walls and, to a lesser extent, in the neural retina. Non-labeled EGF(33-42) significantly inhibited pre-retinal neovascularization in comparison to controls treated with phosphate-buffered saline or scrambled peptide (P < 0.0001). The agonist peptide (Lam beta 1(925-933)) also significantly inhibited proliferative retinopathy; however, it caused a concomitant reduction in retinal ischemia in this model by promoting significant revascularization of the central retina (P < 0.001). Thus, 67LR appears to be an important target receptor for the modulation of retinal neovascularization. Agonism of this receptor may be valuable in reducing the hypoxia-stimulated release of angiogenic growth factors which drives retinal angiogenesis. PMID- 11786423 TI - Induction of myocarditis and valvulitis in lewis rats by different epitopes of cardiac myosin and its implications in rheumatic carditis. AB - Immune responses against cardiac myosin and group A streptococcal M protein have been implicated in the pathogenesis of rheumatic heart disease. Although cardiac myosin is known to produce myocarditis in susceptible animals, it has never been investigated for its role in production of valvular heart disease, the most serious sequelae of group A streptococcal infection in acute rheumatic fever. In our study, cardiac myosin induced valvulitis in the Lewis rat, and epitopes responsible for production of valvulitis were located in the rod region. Human and rat cardiac myosins induced severe myocarditis in the Lewis rats as expected. A purified S2 fragment (amino acid sequences 842 to 1295) produced the most severe myocarditis as well as valvulitis. Different regions of light meromyosin produced valvulitis (residues 1685 to 1936) or myocarditis (residues 1529 to 1611). Because streptococcal M proteins produced valvular heart disease in Lewis rats and have been linked to anti-cardiac myosin responses, we reacted myosin sensitized lymphocytes isolated from the hearts of Lewis rats with peptides of streptococcal M5 protein in tritiated thymidine assays. Infiltrating lymphocytes responded most strongly to peptides within the B repeat region of streptococcal M protein. These data show direct evidence that immune responses against cardiac myosin lead to valvular heart disease and the infiltration of the heart by streptococcal M protein reactive T lymphocytes. PMID- 11786425 TI - Mouse strain modulates the role of the ciliated cell in acute tracheobronchial airway injury-distal airways. AB - Understanding cellular repair mechanisms in vivo has been advanced through the use of well-defined injury and repair models and their application to knockout and transgenic animals, primarily mice generated in a variety of background strains. However, little is known concerning the effect that mouse strain itself has on the interpretation and comparability of observations when the strain used for genetic manipulation is not the strain used to develop the model. We compared acute bronchiolar injury and repair in three strains of mice used in knockout mouse development (C57BL/6, 129/TerSv, and 129/SvEv) to the model strain (Swiss Webster) after treatment with the same dose of naphthalene and sacrificed at 1, 2, 4, 7, and 14 days after treatment. Extent of Clara cell toxicity and exfoliation was identical in the distal airways of all strains. There were significant strain-related differences in ciliated cell squamation, initiation and duration of proliferation, epithelial differentiation, and time to completion of epithelial repair. We conclude that ciliated cells play a prominent role in repair of distal airway injury, but that all phases of the repair process differ by strain. In addition, our findings reinforce that control animals must be of the same strain, ideally litter mates, when transgenic or knockout mice are used for the study of airway repair processes and mechanisms. PMID- 11786426 TI - Inhibition of cytoskeletal assembly by cytochalasin B prevents signaling through tyrosine phosphorylation and secretion triggered by collagen but not by thrombin. AB - Activation of platelets leads to cytoskeletal assembly that is responsible for platelet motility and internal contraction. We have evaluated the involvement of the cytoskeleton in platelet activation by two strong agonists, collagen and thrombin. Activation was assessed by measuring changes in cytoskeletal assembly, externalization of activation-dependent markers and expression of procoagulant activity, and tyrosine phosphorylation of proteins, in both the absence and the presence of cytochalasin B. Activation of platelets with collagen and thrombin induced morphological changes and increased the expression of CD62P, CD63, glycoprotein IV, and binding of annexin V to platelets. Moreover, both activating agents induced actin polymerization, increased the association of other contractile proteins, and promoted tyrosine phosphorylation of multiple proteins, some of which were associated with the cytoskeleton. The presence of cytochalasin B blocked the previous events when collagen was used as the activating agent, although binding of annexin V still occurred. In contrast, platelet response to thrombin was not completely prevented by the presence of cytochalasin B. Thus, activation by collagen requires a functional cytoskeleton to trigger signaling through tyrosine phosphorylation and secretion. This is not the case for thrombin, which is capable of activating signaling mechanisms in the presence of strong inhibitors of cytoskeletal assembly. Moreover, the expression of a procoagulant surface in platelets still occurs even when platelet motility has been inhibited. PMID- 11786427 TI - Expression and gene copy number analysis of ERBB2 oncogene in prostate cancer. AB - An anti-ERBB2 antibody, trastuzumab, has been shown to be highly efficient in the treatment of metastatic breast cancers overexpressing the ERBB2 gene. It has been suggested that overexpression and even amplification of ERBB2 may play a role in the development of prostate cancer. Here, we have analyzed gene copy number and expression of the ERBB2 gene in both androgen-dependent primary and metastatic tumors, as well as recurrent hormone-refractory tumors. The expression levels were compared to the expression of ERBB2 in breast cancers with or without ERBB2 gene amplification. Of 126 prostate tumors, chromogenic in situ hybridization (CISH) revealed only 1 case containing borderline (six to eight copies) amplifications of ERBB2. This hormone-refractory tumor, however, did not express ERBB2 protein. Immunohistochemical staining of ERBB2 protein was negative (0 or 1+ intensity) in all prostate samples (n = 124) analyzed. To quantitate the level of ERBB2 mRNA expression in prostate tumors (n = 34) and cell lines (n = 3), as well as in breast tumors (n = 30) and cell lines (n = 16), real-time reverse transcriptase-polymerase chain reaction (LightCycler) methodology was used. The expression level was similar in all prostate tumor types and corresponded to the level of expression in breast carcinomas without ERBB2 amplification. Breast tumors with ERBB2 amplification expressed, on average, approximately 20 times (P < 0.001) higher mRNA levels than prostate tumors or breast carcinomas without the gene amplification. In conclusion, the expression of ERBB2 in prostate cancer is relatively low, and is not altered during disease progression. Thus, it is unlikely that treatment modalities relying on the overexpression of ERBB2 gene will be useful in treating prostate cancer. PMID- 11786429 TI - Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. AB - Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium. PMID- 11786428 TI - Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue infiltrating lymphocytes. AB - Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation. PMID- 11786430 TI - An alternative promoter of the human neuronal nitric oxide synthase gene is expressed specifically in Leydig cells. AB - Neuronal nitric oxide synthase (nNOS) plays a modulatory role in the biology of a variety of neuroendocrine tissues and is especially relevant to gonadal function. We have previously reported the cloning and characterization of a variant of the nNOS protein, termed testis nNOS (TnNOS), the mRNA for which was restricted in expression to male gonadal tissues. To examine the cell-specificity of the testis specific NOS regulatory regions we defined patterns of beta-galactosidase expression of an insertional transgene in which the reporter gene lacZ was under the transcriptional control of the human TnNOS promoter. beta-galactosidase activity was detected exclusively in the interstitial cells of the testis in transgenic mice. These cells also evidenced positive staining for nNOS protein and were identified as androgen-producing Leydig cells by staining with the Leydig cell marker, P(450)scc. Expression of the promoter was absent in cells of the seminiferous tubules, specifically germline cells of different stages and Sertoli cells. In contrast to the male gonad, beta-galactosidase activity was not detected in ovaries of adult female mice. Activity was also not evident in organs known to express full-length nNOS, such as skeletal muscle, kidney, or cerebellum. The same pattern of beta-galactosidase staining was observed in independent transgenic founders and was distinct from that observed for an endothelial NOS promoter/reporter transgene. In the testis of male adult eNOS promoter-reporter transgenic mice, beta-galactosidase activity was expressed only in endothelial cells of large- and medium-sized arterial blood vessels. Transcriptional activity of the human TnNOS promoter could not be detected in a variety of cell types, including Leydig cells, using episomal promoter-reporter constructs suggesting that a nuclear environment and higher order genomic complexity are required for appropriate promoter function. The restricted expression pattern of an nNOS variant in Leydig cells of the male gonad suggests an important role in the regulation of testosterone release and represents an intriguing model with which to dissect the molecular basis of Leydig cell specific gene expression. PMID- 11786431 TI - Vascular endothelial growth factor, transforming growth factor-alpha, and estrogen receptors: possible cross-talks and interactions. PMID- 11786432 TI - Accurate gene expression measurement in formalin-fixed and paraffin-embedded tumor tissue. PMID- 11786433 TI - Microsatellite instability in colorectal cancer: prognostic, predictive or both? PMID- 11786434 TI - Gathering intelligence on antiplatelet drugs: the view from 30 000 feet. When combined with other information overviews lead to conviction. PMID- 11786435 TI - Treating extremely low birthweight infants with prophylactic indomethacin. Evidence for short term benefits only. PMID- 11786436 TI - Bipolar affective disorder-left out in the cold. Too late for the national service framework but local initiatives may be possible. PMID- 11786437 TI - Clinical networks. Advantages include flexibility, strength, speed, and focus on clinical issues. PMID- 11786438 TI - Helping patients in hospital to quit smoking. Dedicated counselling services are effective--others are not. PMID- 11786439 TI - Drug companies face pressure on profits. PMID- 11786440 TI - US links motor neurone disease with Gulf war service. PMID- 11786445 TI - Dolly's arthritis dents faith in cloning. PMID- 11786447 TI - WHO dissenter warns against plans to retain smallpox virus. PMID- 11786448 TI - Journal "should have revealed scientist's connection to company". PMID- 11786451 TI - Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. AB - OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. DESIGN: Collaborative meta-analyses (systematic overviews). INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed. PMID- 11786452 TI - Brief intervention during hospital admission to help patients to give up smoking after myocardial infarction and bypass surgery: randomised controlled trial. AB - OBJECTIVE: To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems. DESIGN: Randomised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses. SETTING: Inpatient wards in 17 hospitals in England. PARTICIPANTS: 540 smokers admitted to hospital after myocardial infarction or for cardiac bypass surgery who expressed interest in stopping smoking. INTERVENTION: Brief verbal advice and standard booklet (usual care). Intervention lasting 20-30 minutes including carbon monoxide reading, special booklet, quiz, contact with other people giving up, declaration of commitment to give up, sticker in patient's notes (intervention group). MAIN OUTCOME MEASURES: Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points. Feasibility of the intervention and delivery of its components. RESULTS: After six weeks 151 (59%) and 159 (60%) patients remained abstinent in the control and intervention group, respectively (P=0.84). After 12 months the figures were 102 (41%) and 94 (37%) (P=0.40). Recruitment was slow, and delivery of the intervention was inconsistent, raising concerns about the feasibility of the intervention within routine care. Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it (P<0.01). Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome. Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infarction. CONCLUSIONS: Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers. PMID- 11786453 TI - Excess winter mortality: influenza or cold stress? Observational study. PMID- 11786454 TI - Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet. AB - OBJECTIVE: To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics. DESIGN: Nested, single blind, randomised controlled trial. SETTING: Three suburban general practices in Nottingham Participants: 259 previously well adults presenting with acute bronchitis. INTERVENTION: In group A, 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and standard verbal reassurance. Half of them (106) were also given an information leaflet. All patients in group B (47) were judged to need antibiotics and were given a prescription and encouraged to use it. MAIN OUTCOME MEASURES: Antibiotic use in the next two weeks. Reconsultation for the same symptoms in the next month. RESULTS: In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet (49 v 63, risk ratio 0.76, 95% confidence interval 0.59 to 0.97, P=0.04). Numbers reconsulting were similar (11 v 14). In group B, 44 patients took the antibiotics. CONCLUSION: Most previously well adults with acute bronchitis were judged not to need antibiotics. Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use. PMID- 11786455 TI - Performance league tables: the NHS deserves better. PMID- 11786456 TI - Whisking research into the classroom. PMID- 11786457 TI - Evidence based case report. Antibiotic treatment for spontaneous bacterial peritonitis. PMID- 11786458 TI - Preventing atherosclerotic events with aspirin. PMID- 11786459 TI - Cannabis control: costs outweigh the benefits. For. PMID- 11786460 TI - Promoting patient safety in primary care. Honesty and openness may not be best policy. PMID- 11786461 TI - Should NHS patients be allowed to pay extra for their care? Patient payments bring new resources into system. PMID- 11786462 TI - Screening for Down's syndrome. Antenatal screening has human costs. PMID- 11786463 TI - Problems with temporary cardiac pacing. Ultrasonography can aid central venous cannulation. PMID- 11786464 TI - Mental health services for children and adolescents. Raised profile of child health services is welcome. PMID- 11786465 TI - Fabricated or induced illness in children. Open mind is needed regarding origins of childhood symptoms and illnesses. PMID- 11786466 TI - Endometriosis. Emphasis on medical treatment is misleading. PMID- 11786467 TI - Media could be used to better effect than inducing fear. PMID- 11786474 TI - Protease activated receptor 2 and the cardiovascular system. PMID- 11786473 TI - The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. AB - Contraction of smooth muscle is initiated, and to a lesser extent maintained, by a rise in the concentration of free calcium in the cell cytoplasm ([Ca(2+)](i)). This activator calcium can originate from two intimately linked sources--the extracellular space and intracellular stores, most notably the sarcoplasmic reticulum. Smooth muscle contraction activated by excitatory neurotransmitters or hormones usually involves a combination of calcium release and calcium entry. The latter occurs through a variety of calcium permeable ion channels in the sarcolemma membrane. The best-characterized calcium entry pathway utilizes voltage-operated calcium channels (VOCCs). However, also present are several types of calcium-permeable channels which are non-voltage-gated, including the so called receptor-operated calcium channels (ROCCs), activated by agonists acting on a range of G-protein-coupled receptors, and store-operated calcium channels (SOCCs), activated by depletion of the calcium stores within the sarcoplasmic reticulum. In this article we will review the electrophysiological, functional and pharmacological properties of ROCCs and SOCCs in smooth muscle and highlight emerging evidence that suggests that the two channel types may be closely related, being formed from proteins of the Transient Receptor Potential Channel (TRPC) family. PMID- 11786475 TI - CB(1) receptor antagonist SR141716A increases capsaicin-evoked release of Substance P from the adult mouse spinal cord. AB - Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB(1)) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Capsaicin (0.1 - 10 microM) was applied to superfused cord sections and evoked a dose dependent release of SP above basal outflow of (23.36+/-2.96 fmol 8 ml(-1)). Maximum evoked SP release was obtained with 5 microM Capsaicin (262.4+/-20.8 fmol 8 ml(-1)). Higher capsaicin concentrations (50 - 100 microM) evoked less SP release. Superfusion of CB(1) antagonist SR141716A (5 microM) increased evoked SP release with capsaicin (0.1 - 10 microM) and reversed the reducing effect of high dose capsaicin (100 microM). Antagonism of CB(1) receptors in the spinal cord during capsaicin stimulation, is evidence of tonic CB(1) activity inhibiting the release of excitatory transmitters after activation of nociceptive neurones and is also indicative of endocannabinoid production during noxious stimulation. PMID- 11786476 TI - Urotensin II evokes potent vasoconstriction in humans in vivo. AB - The peptide urotensin II (U II) evokes potent vasoconstriction in non-human primates. In human blood vessels studied in vitro variable effects of U II are reported; vasoconstriction, vasodilatation or no response. It is therefore of importance to determine the vascular effect of U II in humans in vivo. U II (0.1 300 pmol min(-1)) was infused into the brachial artery of nine healthy volunteers. Changes in forearm blood flow (FBF) were determined by venous occlusion plethysmography. U II induced dose-dependent reduction in FBF. A threshold response was obtained by 1 pmol min(-1), and the highest dose of U II (300 pmol min(-1)) reduced FBF by 31+/-4% (P<0.01). FBF returned to baseline values within 30 min. This study demonstrates that U II produces potent vasoconstriction in humans in vivo. PMID- 11786477 TI - Blockade of bradykinin B(2) receptor suppresses acute pancreatitis induced by obstruction of the pancreaticobiliary duct in rats. AB - 1. The involvement of bradykinin (BK) B(2) receptor in acute pancreatitis induced by pancreaticobiliary duct ligation was investigated in rats. 2. The activities of amylase and lipase in the serum, the water content of the pancreas, and vacuolization of the acinar cells were significantly increased 2 h after obstruction of the duct in Sprague-Dawley rats. 3. Elevated serum amylase activity, increased pancreatic oedema, and damage of the pancreatic tissue were significantly less marked in plasma kininogen-deficient, B/N-Katholiek rats than in the normal strain, B/N-Kitasato rats 2 h after the ligation. 4. Obstruction of the pancreaticobiliary duct augmented the level of (1-5)-BK (Arg(1)-Pro(2)-Pro(3) Gly(4)-Phe(5)), a stable BK metabolite, in the blood from 73.0+/-21.7 pg ml(-1) at 0 h to 149.8+/-38.0 pg ml(-1) at 2 h after the induction of pancreatitis in SD rats. 5. Administration of a BK B(2) receptor antagonist, FR173657 (100 mg kg( 1), p.o.) or Hoe140 (100 nmol kg(-1), s.c.), reduced the elevation of amylase and lipase activities in the serum and of pancreatic water content in a dose dependent manner. The effective attenuation of oedema formation and vacuolization by the antagonists was also confirmed light-microscopically. In contrast, treatment with gabexate mesilate or indomethacin did not cause significant suppression of the pancreatitis. 6. These findings suggest a possible involvement of kinin B(2) receptor in the present pancreatitis model. Furthermore, they point to the potential usefulness of the B(2) receptor in clinical acute pancreatitis. PMID- 11786478 TI - Magnolol attenuates VCAM-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in the aorta of cholesterol-fed rabbits. AB - 1. In a previous study, we showed that magnolol, a potent antioxidant derived from a Chinese herb, attenuates monocyte chemotactic protein-1 (MCP-1) expression and intimal hyperplasia in the balloon-injured aorta of cholesterol-fed rabbits. Expression of cell adhesion molecules by the arterial endothelium and the attachment of leukocytes to the endothelium may play a major role in atherosclerosis. In the present study, the effects of magnolol on the expression of endothelial-leukocyte adhesion molecules and the activation of nuclear factor kappa B (NF-kappa B) in tumour necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs) were investigated. 2. Pretreatment of HAECs with magnolol (5 microM) significantly suppressed the TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) (64.8+/-1.9%), but had no effect on the expression of intercellular cell adhesion molecule-1 and endothelial cell selectin. 3. Magnolol (5 and 10 microM) significantly reduced the binding of the human monocytic cell line, U937, to TNF-alpha-stimulated HAECs (58.4 and 56.4% inhibition, respectively). Gel shift assays using the (32)P-labelled NF-kappa B consensus sequence as probe showed that magnolol pretreatment reduced the density of the shifted bands seen after TNF-alpha-induced activation. Immunoblot analysis and immunofluorescence staining of nuclear extracts demonstrated a 58% reduction in the amount of NF-kappa B p65 in the nuclei in magnolol-treated HAECs. Magnolol also attenuated intracellular H(2)O(2) generation in both control and TNF-alpha treated HAECs. 4. Furthermore, in vivo, magnolol attenuates the intimal thickening and TNF-alpha and VCAM-1 protein expression seen in the thoracic aortas of cholesterol-fed rabbits. 5. Taken together, these data demonstrate that magnolol inhibits TNF-alpha-induced nuclear translocation of NF-kappa B p65 and thereby suppresses expression of VCAM-1, resulting in reduced adhesion of leukocytes. These results suggest that magnolol has anti-inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory responses in vivo. PMID- 11786479 TI - Endothelium-dependent hyperpolarization and relaxation in mesenteric arteries of middle-aged rats: influence of oestrogen. AB - 1. We determined whether gender and/or oestrogen deficiency affect endothelium dependent hyperpolarization and relaxation in mesenteric arteries isolated from middle-aged (44 - 45 week old) rats. 2. The hyperpolarizing response to acetylcholine (ACh) was significantly greater in females than in males. Ovariectomy caused a marked reduction in ACh-induced hyperpolarization in female arteries, and this was improved by 17 beta-oestradiol replacement therapy. 3. ACh induced relaxations in female arteries were not significantly different from those observed in male rats, and were unaffected by ovariectomy, regardless of whether indomethacin was present. However, when endothelial nitric oxide synthase (eNOS) was blocked with N(G)-nitro-L-arginine, the sensitivity and maximum relaxant response to ACh was significantly higher in intact females compared with males and ovariectomized females. Treatment with 17 beta-oestradiol prevented the reduced vasorelaxant response in ovariectomized females. 4. Immunohistochemical examination for eNOS showed no apparent difference in eNOS protein expression in the endothelium of arteries between intact and ovariectomized females. 5. Since circulating concentrations of oestrogen were essentially low in middle-aged female rats, the present results suggest that subtle changes from a critical concentration of oestrogen at this age may strongly affect the vascular actions of endothelium-derived hyperpolarizing factor without effect on eNOS expression and activity. PMID- 11786480 TI - The antiarrhythmic effects of ischaemic preconditioning in anaesthetized dogs are prevented by atropine; role of changes in baroreceptor reflex sensitivity. AB - 1. Dogs, anaesthetized with chloralose and urethane, were subjected to a 25 min occlusion of the left anterior descending coronary artery. This resulted in ventricular ectopic activity, a reduction in baroreflex sensitivity (BRS, measured following the intravenous administration of phenylephrine), elevations in the epicardial ST-segment and increases in the degree of inhomogeneity of electrical activation, both measured from the ischaemic region of the left ventricular wall. 2. These changes were markedly reduced when the 25 min occlusion was preceded, 20 min earlier, by a 5 min (preconditioning) occlusion of the same coronary artery (e.g. VF during ischaemia reduced from 40% in the controls to 0%; P<0.05; BRS increased from 1.22+/-0.23 pre-occlusion to 1.61+/ 0.25 mmHg ms(-1) post-occlusion in preconditioned dogs; cf. 1.28+/-0.29 to 0.45+/ 0.12 mmHg ms(-1) respectively in the controls, P<0.05). 3. These beneficial effects of preconditioning were prevented by the administration, 10 min prior to the 25 min coronary artery occlusion, of atropine (1 mg kg(-1) i.v. followed by a continuous infusion of 0.04 mg kg(-1) h(-1)). For example, VF during occlusion was increased from 0% in the preconditioned dogs to 40% (P<0.05) in the presence of atropine and BRS was again reduced during occlusion (from 1.75+/-0.29 to 0.30+/-0.08 mmHg ms(-1); P<0.05). 4. We conclude that preconditioning reduces arrhythmia severity during ischaemia by favourably modifying cardiac autonomic receptor mechanism through enhancing vagal influences. PMID- 11786481 TI - Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors. AB - 1. The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 - 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 - 3 mg kg(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 - 3 Hz with decreases in power at higher frequencies (9 - 30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 - 0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 - 10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 3 Hz in prefrontal cortex. PMID- 11786482 TI - Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells. AB - 1. This study was performed to determine the effect and action mechanisms of sodium butyrate (NaB) on the growth of breast cancer cells. 2. Butyrate inhibited the growth of all breast cancer cell lines analysed. It induced cell cycle arrest in G1 and apoptosis in MCF-7, MCF-7ras, T47-D, and BT-20 cells, as well as arrest in G2/M in MDA-MB-231 cells. 3. Transient transfection of MCF-7 and T47-D cells with wild-type and antisense p53 did not modify butyrate-induced apoptosis. Pifithrin-alpha, which inhibits the transcriptional activity of P53, did not modify cell growth or apoptosis of MCF-7 and T47-D cells treated with butyrate. These results indicate that P53 was not involved in butyrate-induced growth inhibition of breast cancer cells. 4. Treatment of MCF-7 cells with anti-Fas agonist antibody induced cell death, indicating that Fas was functional in these cells. Moreover, butyrate potentiated Fas-induced apoptosis, as massive apoptosis was observed rapidly when MCF-7 cells were treated with butyrate and anti-Fas agonist antibody. In addition, butyrate-induced apoptosis in MCF-7 cells was considerably reduced by anti-Fas antagonist antibody. Western blot analysis showed that butyrate increased Fas and Fas ligand levels (Fas L), indicating that butyrate-induced apoptosis may be mediated by Fas signalling. 5. These results demonstrate that butyrate inhibited the growth of breast cancer cells in a P53 independent manner. Moreover, it induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. These findings may open interesting perspectives in human breast cancer treatment strategy. PMID- 11786483 TI - Angiotensin AT(1) receptor signalling modulates reparative angiogenesis induced by limb ischaemia. AB - 1. The concept that angiotensin II exerts pro-angiogenic activity is not universally accepted. We evaluated whether inhibition of the renin-angiotensin system (RAS) would influence reparative angiogenesis in a murine model of limb ischaemia. 2. Perfusion recovery following surgical removal of the left femoral artery was analysed by laser Doppler flowmetry in mice given the ACE inhibitor ramipril (1 mg kg(-1) per day), the AT(1) antagonist losartan (15 mg kg(-1) per day), or vehicle. Muscular capillarity was examined at necroscopy. Ramipril induced effects were also studied under combined blockade of kinin B(1) and B(2) receptors. Furthermore, the effects of ischaemia on AT(1) gene expression and ACE activity were determined. 3. In untreated mice, muscular AT(1a) gene expression was transiently decreased early after induction of limb ischaemia, whereas AT(1b) mRNA was up-regulated. ACE activity was reduced in ischaemic muscles at 1 and 3 days. Gene expression of AT(1) isoforms as well as ACE activity returned to basal values by day 14. Spontaneous neovascularization allowed for complete perfusion recovery of the ischaemic limb after 21 days. 4. Reparative angiogenesis was negatively influenced by either ramipril (P<0.02) or losartan (P<0.01), leading to delayed and impaired post-ischaemic recovery (50 - 70% less compared with controls). Ramipril-induced effects remained unaltered under kinin receptor blockade. 5. The present study indicates that (a) expression of angiotensin II AT(1) receptors and ACE activity are modulated by ischaemia, (b) ACE-inhibition or AT(1) antagonism impairs reparative angiogenesis, and (c) intact AT(1) receptor signalling is essential for post-ischaemic recovery. These results provide new insights into the role of the RAS in vascular biology and suggest cautionary use of ACE inhibitors and AT(1) antagonists in patients at risk for developing peripheral ischaemia. PMID- 11786484 TI - Bi-directional transport of GABA in human embryonic kidney (HEK-293) cells stably expressing the rat GABA transporter GAT-1. AB - 1. Bi-directional GABA-transport was studied by performing uptake and superfusion experiments in human embryonic kidney 293 cells stably expressing the rat GABA transporter rGAT-1. 2. K(M) and V(max) values for [(3)H]-GABA uptake were 11.7+/ 1.8 microM and 403+/-55 pmol min(-1) 10(-6) cells (n=9), respectively. 3. Kinetic analysis of outward transport was performed by pre-labelling the cells with increasing concentrations of [(3)H]-GABA and triggering outward transport with 333 microM GABA. Approximate apparent K(M) and V(max) values were 12 mM and 50 pmol min(-1) 10(-6) cells, respectively. 4. GABA re-uptake inhibitors (RI; e.g. tiagabine), as well as, substrates of the rGAT-1 (e.g. GABA, nipecotic acid) concentration dependently decreased [(3)H]-GABA uptake and increased efflux of [(3)H]-GABA from pre-labelled cells. The IC(50) values for inhibiting uptake and the EC(50) values for increasing efflux were significantly correlated (r(2)=0.99). 5. On superfusion, RI antagonized the efflux-enhancing effect of the substrates. The effect of the latter was markedly augmented in the presence of ouabain (100 microM), whereas the effect of RI remained unchanged. The most likely explanation for the release enhancing effect of RI is interruption of ongoing re-uptake. 6. The structural GABA-analogue 2,4-diamino-n-butyric acid (DABA) exhibited a bell-shaped concentration response curve on [(3)H]-GABA efflux with the maximum at 1 mM, and displayed a deviation from the sigmoidal inhibition curve in uptake experiments in the same concentration range. At concentrations below 1 mM, DABA inhibited [(3)H]-GABA uptake non-competitively, while at 1 mM and above the inhibition of uptake followed a competitive manner. 7. The results provide information of GABA inward and outward transport, and document a complex interaction of the rGAT-1 with its substrate DABA. PMID- 11786485 TI - Effect of NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window. AB - 1. The efficacy of the free radical trapping agent NXY-059 in reducing the infarct volume following both transient and permanent focal ischaemia has been examined in rats. 2. In the transient ischaemia model, rats were subjected to a 2 h occlusion of the middle cerebral artery (MCA). Intravenous infusion of NXY-059 (1, 10 and 30 mg kg(-1) h) for 21.75 h starting 2.25 h after the occlusion, produced a dose-dependent decrease in both neurological impairment and the histologically measured infarct volume (a mean 59% decrease at 10 mg kg(-1) h). 3. In the permanent ischaemia model, animals were injected (s.c.) with a loading dose of NXY-059 of 32.5, 53.8 or 75.4 mg kg(-1) and osmotic minipumps were implanted which had been primed to deliver respectively 30, 50 or 70 mg kg(-1) h. When treatment was initiated 5 min after MCA occlusion there was a dose dependent protection of both cortical and sub-cortical tissue (cortex: 63% at the mid-range dose). Protection was related linearly to plasma concentration (plasma unbound NXY-059 concentration at 1 h: 37+/-16 micromol l(-1) at the mid-range dose). 4. When the mid range dose was administered between 5 min - 4 h after MCA occlusion, a marked and statistically significant protection was seen at all time points (44% protection in cortex at 4 h). 5. These data demonstrate the substantial neuroprotective efficacy of NXY-059 at plasma concentrations that can be achieved clinically and indicate that NXY-059 also has a therapeutic window of opportunity that is clinically relevant. PMID- 11786486 TI - Assessing the emetic potential of PDE4 inhibitors in rats. AB - 1. Type 4 phosphodiesterase (PDE4) inhibitors mimic the pharmacological actions of alpha(2)-adrenoceptor antagonists. This has been postulated as the mechanism by which PDE4 inhibitors induce emesis and was also demonstrated by their ability to reverse xylazine/ketamine-induced anaesthesia. We further characterized this latter effect since it appears to reflect the emetic potential of PDE4 inhibitors. 2. Selective inhibitors of PDE 1, 2, 3, 4 and 5 were studied in rats, on the duration of anaesthesia induced by the combination of xylazine (10 mg kg( 1), i.m.) and ketamine (10 mg kg(-1), i.m.). PMNPQ (i.e. 6-(4-pyridylmethyl)-8-(3 nitrophenyl)quinoline) - PDE4 inhibitor: 0.01 - 3 mg kg(-1)), like MK-912 (alpha(2)-adrenoceptor antagonist: 0.01 - 3 mg kg(-1)), dose-dependently reduced the duration of anaesthesia. In contrast, vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor), milrinone (PDE3 inhibitor) and zaprinast (PDE5 inhibitor) had no significant effect at the doses tested (1 - 10 mg kg(-1)). Analysis of plasma and cerebrospinal fluid (CSF) of treated animals confirmed the absorption and distribution to the brain of the inactive inhibitors. 3. Neither MK-912 (3 mg kg( 1)) nor PMNPQ (0.1 - 1 mg kg(-1)) altered the duration of anaesthesia induced via a non-alpha(2)-adrenoceptor pathway (sodium pentobarbitone 50 mg kg(-1), i.p.). 4. Central NK(1) receptors are involved in PDE4 inhibitor-induced emesis. Consistently, [sar(9), Met(O(2))(11)]-substance P (NK(1) receptor agonist, 6 microg i.c.v.) reduced the duration of anaesthesia induced by xylazine/ketamine. 5. In summary, this model is functionally coupled to PDE4, specific to alpha(2) adrenoceptors and relevant to PDE4 inhibitor-induced emesis. It therefore provides a novel way of evaluating the emetic potential of PDE4 inhibitors in rats. PMID- 11786487 TI - Capacitative Ca(2+) entry in vascular endothelial cells is mediated via pathways sensitive to 2 aminoethoxydiphenyl borate and xestospongin C. AB - 1. Agonists increase endothelial cell intracellular Ca(2+), in part, by capacitative entry, which is triggered by the filling state of intracellular Ca(2+) stores. It has been suggested that depletion of endoplasmic reticulum (ER) Ca(2+) stores either leads to a physical coupling between the ER and a plasma membrane channel, or results in production of an intracellular messenger which affects the gating of membrane channels. As an axis involving the IP(3) receptor has been implicated in a physical coupling mechanism the aim of this study was to examine the effects of the putative IP(3) receptor antagonists/modulators, 2 aminoethoxydiphenyl borate (2APB) and xestospongin C, on endothelial cell Ca(2+) entry. 2. Studies were conducted in fura 2 loaded cultured bovine aortic endothelial cells and endothelial cells isolated from rat heart. 3. 2APB (30 - 300 microM) inhibited Ca(2+) entry induced by both agonists (ATP 1 microM, bradykinin 0.1 microM) and receptor-independent mechanisms (thapsigargin 1 microM, ionomycin 0.5 and 5 microM). 2APB did not diminish endothelial cell ATP induced production of IP(3) nor effect in vitro binding of [(3)H]-IP(3) to an adrenal cortex binding protein. Capacitative Ca(2+) entry was also blocked by disruption of the actin cytoskeleton with cytochalasin (100 nM) while the initial Ca(2+) release phase was unaffected. 4. Similarly to 2APB, xestospongin C (3 - 10 microM) inhibited ATP-induced Ca(2+) release and capacitative Ca(2+) entry. Further, xestospongin C inhibited capacitative Ca(2+) entry induced by thapsigargin (1 microM) and ionomycin (0.5 microM). 5. The data are consistent with a mechanism of capacitative Ca(2+) entry in vascular endothelial cells which requires (a) IP(3) receptor binding and/or an event distal to the activation of the ER receptor and (b) a spatial relationship, dictated by the cytoskeleton, between Ca(2+) release and entry pathways. PMID- 11786488 TI - The role of beta(3)-adrenoceptors in mediating relaxation of porcine detrusor muscle. AB - 1. beta-adrenoceptors mediate relaxation of bladder detrusor smooth muscle. This study investigates the contribution of beta(3)-adrenoceptors to relaxation of the pig urinary bladder. 2. Cell membranes were prepared from detrusor muscle of the pig bladder dome and competition experiments with [(3)H]-dihydroalprenolol (DHA), a non-selective beta-adrenoceptor antagonist was used as a specific radioligand to determine the presence of beta-adrenoceptor subtypes. In functional experiments, isolated detrusor muscle strips were used to determine the potency of agonists and the affinity of antagonists. 3. In competition binding experiments, CGP20712A (beta(1)-adrenoceptor selective) displaced [(3)H]-DHA from a single binding site with a low affinity. In contrast, displacement data for ICI 118551 (beta(2)-adrenoceptor antagonist) and SR59230A (beta(3)-adrenoceptor antagonist) best fitted a two-site model suggesting a predominant (70%) population of beta(3)-adrenoceptors. 4. In functional studies, isoprenaline and salbutamol (beta(2)-adrenoceptor agonist) relaxed KCl precontracted muscle strips with high potency (pEC(50) 7.7 and 7.2, respectively), whilst CGP12177 and BRL37344 (beta(3)-adrenoceptor agonists) had low potency and were partial agonists. CGP20712A and atenolol (beta(1)-adrenoceptor antagonists) antagonised responses with a low affinity. ICI118551 antagonized responses to isoprenaline and salbutamol with a high affinity (pK(B)=7.8 and 8.7, respectively), but the Schild slopes were low suggesting that responses were mediated by more than one beta-adrenoceptor. The Schild plot for SR59230A was biphasic, apparent pK(B) values for 3 - 10 nM SR59230A being 8.6 and those for 30 nM - 1 microM being 7.7. 5. These data suggest that beta(3)-adrenoceptors are the predominant beta adrenoceptor subtype present in the pig bladder and that beta-adrenoceptor mediated responses of this tissue are mediated via both the beta(2)- and beta(3) adrenoceptor subtypes. PMID- 11786489 TI - Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach. AB - 1. This study investigates whether the cholinergic neurones, innervating the human proximal stomach, can be modulated by nitric oxide (NO) or vasoactive intestinal polypeptide (VIP), or via presynaptic muscarinic, alpha(2)- or 5 hydroxytryptamine(4) (5-HT(4)-) receptors. 2. Circular muscle strips, without mucosa, were incubated with [(3)H]-choline to incorporate [(3)H]-acetylcholine into the cholinergic transmitter stores. The basal and electrically-induced release of tritium and [(3)H]-acetylcholine were analysed in a medium containing guanethidine (4 x 10(-6) M), hemicholinium-3 (10(-5) M), physostigmine (10(-5) M) and atropine (10(-6) M). Tissues were stimulated twice for 2 min (S(1) and S(2): 40 V, 1 ms, 4 Hz) and drugs were added before S(2). 3. The NO synthase inhibitor L-N(G)-nitroarginine methyl ester (3 x 10(-4) M) and the NO donor sodium nitroprusside (10(-5) M), as well as VIP (10(-7) M) did not influence the basal release nor the electrically-evoked release. 4. The alpha(2)-adrenoceptor agonist UK-14,304 (10(-5) M) significantly inhibited the electrically-evoked release of [(3)H]-acetylcholine, and this was prevented by the alpha(2)-adrenoceptor antagonist rauwolscine (2 x 10(-6) M). 5. The 5-HT(4)-receptor agonist prucalopride (3 x 10(-7) M) significantly enhanced the electrically-evoked release of [(3)H]-acetylcholine, and the 5-HT(4)-receptor antagonist SB204070 (10(-9) M) prevented this. 6. When atropine (10(-6) M) was omitted from the medium and added before the second stimulation, it significantly increased the release of [(3)H]-acetylcholine. 7. These results suggest that the release of acetylcholine from the cholinergic neurones, innervating the circular muscle in the human proximal stomach, can be inhibited via presynaptic muscarinic auto receptors and alpha(2)-adrenoceptors, and stimulated via presynaptic 5-HT(4) receptors. No evidence for modulation by NO or VIP was obtained. PMID- 11786491 TI - Multiple mechanisms of vascular smooth muscle relaxation by the activation of proteinase-activated receptor 2 in mouse mesenteric arterioles. AB - 1. Activation of PAR2 in second-order mesenteric arteriole (MA) rings from C57BL/6J, NOS3 (-/-) and PAR2 (-/-) mice was assessed for the contributions of NO, cyclo-oxygenases, guanylyl cyclase, adenylyl cyclase, and of K(+) channel activation to vascular smooth muscle relaxation. 2. PAR2 agonist, SLIGRL-NH(2) (0.1 to 30 microM), induced relaxation of cirazoline-precontracted MA from C57BL/6J and NOS3 (-/-), but not PAR2 (-/-) mice. Maximal relaxation (E(max)) was partially reduced by a combination of L-(G)N-nitroarginine methyl ester (L-NAME), 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and indomethacin. An ODQ/L NAME/indomethacin resistant relaxation was also caused by trypsin (30 nM) in PAR2 (+/+), but not in PAR2 (-/-) mice. Relaxation was endothelium-dependent and inhibited by either 30 mM KCl-precontraction, or pretreatment with apamin, charybdotoxin, and their combination; iberiotoxin did not substitute for charybdotoxin nor did scyllatoxin substitute fully for apamin. 3. Tetraethylammonium (TEA), glibenclamide, tetrodotoxin, 17-octadecynoic acid, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide, SQ22536, carbenoxolone, arachidonyl trifluoromethyl ketone, 7-nitroindazole, N-(3 (aminomethyl)benzyl)acetamidine (1400W), N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) and propanolol did not inhibit relaxation. 4 aminopyridine significantly increased the potency of SLIGRL-NH(2). A combination of 30 microM BaCl(2) and 10 microM ouabain significantly reduced the potency for relaxation, and in the presence of L-NAME, ODQ and indomethacin, E(max) was reduced. 4. We conclude PAR2-mediated relaxation of mouse MA utilizes multiple mechanisms that are both NO-cGMP-dependent, and -independent. The data are also consistent with a role for endothelium-dependent hyperpolarization of vascular smooth muscle that involves the activation of an apamin/charybdotoxin-sensitive K(+) channel(s) and, in part, may be mediated by K(+). PMID- 11786490 TI - Tissue-specific expression of human lipoprotein lipase in the vascular system affects vascular reactivity in transgenic mice. AB - 1. The role of smooth muscle-derived lipoprotein lipase (LPL) that translocates to the endothelium surface on vascular dysfunction during atherogenesis is unclear. Thus, the role of vascular LPL on blood vessel reactivity was assessed in transgenic mice that specifically express human LPL in the circulatory system. 2. Aortic free fatty acids (FFAs) were increased by 69% in the transgenic mice expressing human LPL in aortic smooth muscle cells (L2LPL) compared with their non-transgenic littermates (L2). 3. Contractility to KCl was increased by 33% in aortae of L2LPL mice. Maximal contraction to phenylephrine (PE) was comparable in L2 and L2LPL animals, while the frequency of tonus oscillation to PE increased by 104% in L2LPL mice. 4. In L2LPL animals, *NO mediated relaxation to acetylcholine (ACh) and ATP was reduced by 47 and 32%, respectively. In contrast, endothelium independent relaxation to sodium nitroprusside (SNP) was not different in both groups tested. 5. ATP-initiated Ca(2+) elevation that triggers *NO formation was increased by 41% in single aortic endothelial cells freshly isolated from L2LPL animals. 6. In aortae from L2LPL mice an increased *O(2)(-) release occurred that was normalized by removing the endothelium and by the NAD(P)H oxidase inhibitor DPI and the PKC inhibitor GF109203X. 7. The reduced ACh-induced relaxation in L2LPL animals was normalized in the presence of SOD, indicating that the reduced relaxation is due, at least in part, to enhanced *NO scavenging by *O(2)(-). 8. These data suggest that despite normal lipoprotein levels increased LPL-mediated FFAs loading initiates vascular dysfunction via PKC-mediated activation of endothelial NAD(P)H oxidase. Thus, vascular LPL activity might represent a primary risk factor for atherosclerosis independently from cholesterol/LDL levels. PMID- 11786492 TI - The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats. AB - 1. The pharmacology of the acute hyperthermia that follows 3,4 methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats has been investigated. 2. MDMA (12.5 mg kg(-1) i.p.) produced acute hyperthermia (measured rectally). The tail skin temperature did not increase, suggesting that MDMA may impair heat dissipation. 3. Pretreatment with the 5-HT(1/2) antagonist methysergide (10 mg kg(-1)), the 5-HT(2A) antagonist MDL 100,907 (0.1 mg kg(-1)) or the 5-HT(2C) antagonist SB 242084 (3 mg kg(-1)) failed to alter the hyperthermia. The 5-HT(2) antagonist ritanserin (1 mg kg(-1)) was without effect, but MDL 11,939 (5 mg kg(-1)) blocked the hyperthermia, possibly because of activity at non-serotonergic receptors. 4. The 5-HT uptake inhibitor zimeldine (10 mg kg(-1)) had no effect on MDMA-induced hyperthermia. The uptake inhibitor fluoxetine (10 mg kg(-1)) markedly attenuated the MDMA-induced increase in hippocampal extracellular 5-HT, also without altering hyperthermia. 5. The dopamine D(2) antagonist remoxipride (10 mg kg(-1)) did not alter MDMA-induced hyperthermia, but the D(1) antagonist SCH 23390 (0.3 - 2.0 mg kg(-1)) dose dependently antagonized it. 6. The dopamine uptake inhibitor GBR 12909 (10 mg kg( 1)) did not alter the hyperthermic response and microdialysis demonstrated that it did not inhibit MDMA-induced striatal dopamine release. 7. These results demonstrate that in vivo MDMA-induced 5-HT release is inhibited by 5-HT uptake inhibitors, but MDMA-induced dopamine release may not be altered by a dopamine uptake inhibitor. 8. It is suggested that MDMA-induced hyperthermia results not from MDMA-induced 5-HT release, but rather from the increased release of dopamine that acts at D(1) receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia. PMID- 11786493 TI - Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. AB - 1. The antiinflammatory activity of synthetic cannabinoid nabilone in the rat model of carrageenan-induced acute hindpaw inflammation was compared with that of the endocannabinoid palmitoylethanolamide and the nonsteroidal antiinflammatory drug indomethacin. 2. Preliminary experiments in rats used a tetrad of behavioural tests, specific for tetrahydrocannabinol-type activity in the CNS. These showed that the oral dose of nabilone 2.5 mg kg(-1) had no cannabinoid psychoactivity. 3. Intraplantar injection of carrageenan (1% w v(-1)) elicited a time-dependent increase in paw volume and thermal hyperalgesia. 4. Nabilone (0.75, 1.5, 2.5 mg kg(-1), p.o.), given 1 h before carrageenan, reduced the development of oedema and the associated hyperalgesia in a dose-related manner. Nabilone 2.5 mg kg(-1), palmitoylethanolamide 10 mg kg(-1) and indomethacin 5 mg kg(-1), given p.o. 1 h before carrageenan, also reduced the inflammatory parameters in a time-dependent manner. 5. The selective CB(2) cannabinoid receptor antagonist [N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1]heptan-2-yl]-5 (4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide] (SR 144528), 3 mg kg(-1) p.o. 1 h before nabilone and palmitoylethanolamide, prevented the anti-oedema and antihyperalgesic effects of the two cannabinoid agonists 3 h after carrageenan. 6. Our findings show the antiinflammatory effect of nabilone and confirm that of palmitoylethanolamide indicating that these actions are mediated by an uncharacterized CB(2)-like cannabinoid receptor. PMID- 11786494 TI - Enhancement of nitric oxide production by methylecgonidine in cultured neonatal rat cardiomyocytes. AB - 1. In the present experiments, we investigated the effects of methylecgonidine (MEG) on nitric oxide (NO) production in cultured neonatal rat cardiomyocytes. Incubation of cultured cardiomyocytes with carbachol or MEG for 48 h significantly enhanced NO production. No release was increased from 1.48+/-0.13 microM (mg protein)(-1) for control to 5.73+/-0.19 microM (mg protein)(-1) for 1 microM carbachol treated cells (P<0.001). In addition, incubation with 1 microM MEG enhanced NO production to 5.55+/-0.28 microM (mg protein)(-1). The effects of MEG on NO production were concentration-dependent. The muscarinic antagonist atropine prevented the enhancement of NO production induced by carbachol or MEG. Compared to MEG-induced NO production, cocaine was much less potent. 2. The enhancement of NO production by carbachol or MEG was even greater in cultured cardiomyocytes transfected with the M(2) cDNA. After 48-h incubation with 1 microM carbachol or 1 microM MEG, NO production was increased by 6.5 and 6.7 fold, respectively, in cardiomyocytes overexpressing M(2) receptors. Coincubation with atropine or N(G)-nitro-L-arginine methyl ester abolished the enhancement of NO production. In contrast, NO production enhanced by carbachol or MEG in M(1)- or M(3)-transfected cardiomyocytes was similar to the level in non-transfected cells. 3. Western blot analysis showed that the protein levels of M(1), M(2), and M(3) were significantly increased in cardiomyocytes transfected with the receptor cDNAs, but MEG had no effect on the expressions. It is interesting that both carbachol and MEG caused a significant increase in constitutive endothelial NO synthase (eNOS) only in M(2)-transfected cardiomyocytes, not in non-transfected, M(1)- or M(3)-transfected cells. Again, atropine blocked the MEG-produced induction of eNOS. 4. Our data demonstrate that MEG significantly enhanced NO production in cultured cardiomyocytes and that the enhancement of NO production may result from MEG stimulation of muscarinic M(2) receptors. PMID- 11786495 TI - Mechanical and electrophysiological effects of endothelin-1 on guinea-pig isolated lower oesophageal sphincter circular smooth muscle. AB - 1. The effects of endothelin-1 (ET-1) on guinea-pig lower oesophageal sphincter (LOS) circular smooth muscle were investigated by using intracellular microelectrodes and isometric tension recording techniques. 2. ET-1 produced biphasic mechanical responses; an initial transient relaxation followed by a sustained contraction. The initial relaxation was not inhibited by either tetrodotoxin (TTX, 1 microM) or L-N(G)-nitroarginine (L-NOARG, 100 microM). The sustained contraction was greatly attenuated by nifedipine (1 microM). 3. ET-1 (1 - 30 nM) induced a concentration-dependent hyperpolarisation that was unaffected by TTX or L-NOARG. The ET(A) receptor antagonist, BQ123 (0.3 microM) abolished the ET-1-induced hyperpolarisation, whereas the ET(B) receptor antagonist, BQ788 (0.3 microM) had no detectable effect. Sarafotoxin S6c (10 nM) did not change the membrane potential. 4. The ET-1-induced hyperpolarisation was abolished by apamin (0.1 microM). Interestingly, apamin abolished the ET-1-induced transient relaxation but potentiated the sustained contraction. 5. In Ca(2+)-free Krebs solution, the ET-1-induced hyperpolarisation was greatly attenuated and returned to the control value when the tissue was reperfused with Krebs solution containing Ca(2+). The ET-1-induced hyperpolarisation was insensitive to nifedipine but was attenuated by SK&F 96365 (1 - [beta-[3-(4 - methoxy - phenyl)propoxy] - 4 - methoxyphenethyl] - 1H-imidazole hydrochloride, 50 microM), an inhibitor of receptor-mediated Ca(2+) entry. The residual component of the ET 1-induced hyperpolarisation was sensitive to thapsigargin (1 microM). 6. These results demonstrate that, in guinea-pig LOS circular smooth muscle, ET-1 hyperpolarizes the membrane by activating apamin-sensitive K(+) channels, mainly as a result of receptor-mediated Ca(2+) entry and partly by Ca(2+) release from intracellular stores. The hyperpolarisation triggers the initial transient relaxation, which acts to oppose the sustained contraction. PMID- 11786496 TI - Pathological role of a constitutively active population of alpha(1D) adrenoceptors in arteries of spontaneously hypertensive rats. AB - 1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2. In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of alpha(1D) adrenoceptors only in some vessels of SHR. 3. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of alpha(1D)-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. 4. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. 5. The increase in the functional role of alpha(1D)-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active alpha(1D) adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID- 11786497 TI - Mu and Delta opioid receptors activate the same G proteins in human neuroblastoma SH-SY5Y cells. AB - 1. There is evidence for interactions between mu and delta opioid systems both in vitro and in vivo. This work examines the hypothesis that interaction between these two receptors can occur intracellularly at the level of G protein in human neuroblastoma SH-SY5Y cells. 2. The [(35)S]GTP gamma S binding assay was used to measure G protein activation following agonist occupation of opioid receptors. The agonists DAMGO (EC(50), 45 nM) and SNC80 (EC(50), 32 nM) were found to be completely selective for stimulation of [(35)S]-GTP gamma S binding through mu and delta opioid receptors respectively. Maximal stimulation of [(35)S]-GTP gamma S binding produced by SNC80 was 57% of that seen with DAMGO. When combined with a maximally effective concentration of DAMGO, SNC80 caused no additional [(35)S] GTP gamma S binding. This effect was also seen when measured at the level of adenylyl cyclase. 3. Receptor activation increased the dissociation of pre-bound [(35)S]-GTP gamma S. In addition, the delta agonist SNC80 promoted the dissociation of [(35)S]-GTP gamma S from G proteins initially labelled using the mu agonist DAMGO. Conversely, DAMGO promoted the dissociation of [(35)S]-GTP gamma S from G proteins initially labelled using SNC80. 4. Tolerance to DAMGO and SNC80 in membranes from cells exposed to agonist for 18 h was homologous and there was no evidence for alteration in G protein activity. 5. The findings support the hypothesis that mu- and delta-opioid receptors share a common G protein pool, possibly through a close organization of the two receptors and G protein at the plasma membrane. PMID- 11786498 TI - Expression of mRNA and functional alpha(1)-adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons. AB - 1. Locus coeruleus neurons in adult rats express binding sites and mRNA for alpha(1)-adrenoceptors even though the depolarizing effect of alpha(1) adrenoceptor agonists on neonatal neurons disappears during development. 2. In this study intracellular microelectrodes were used to record from locus coeruleus neurons in brain slices of adult rats and reverse transcription-polymerase chain reaction (RT - PCR) was used to investigate the mRNA expression of alpha(1)- and alpha(2)-adrenoceptors in juvenile and adult rats. 3. The alpha(1)-adrenoceptor agonist phenylephrine had no effect on the membrane conductance of locus coeruleus neurons (V(hold) -60 mV) but decreased the G protein coupled, inward rectifier potassium (GIRK) conductance induced by alpha(2)-adrenoceptor or mu opioid agonists. The GIRK conductance induced by noradrenaline was increased in amplitude when alpha(1)-adrenoceptors were blocked with prazosin. 4. RT - PCR of total cellular RNA isolated from microdissected locus coeruleus tissue demonstrated strong mRNA expression of alpha(1a)-, alpha(1b)- and alpha(1d) adrenoceptors in both juvenile and adult rats. However, only mRNA transcripts for the alpha(1b)-adrenoceptors were consistently detected in cytoplasmic samples taken from single locus coeruleus neurons of juvenile rats, suggesting that this subtype may be responsible for the physiological effects seen in juvenile rats. 5. Juvenile and adult locus coeruleus tissue expressed mRNA for the alpha(2a)- and alpha(2c)-adrenoceptors while the alpha(2b)-adrenoceptor was only weakly expressed in juveniles and was not detected in adults. 6. The results of this study show that alpha(1)-adrenoceptors expressed in adult locus coeruleus neurons function to suppress the GIRK conductance that is activated by mu-opioid and alpha(2)-adrenoceptors. PMID- 11786499 TI - Pharmacological properties of nociceptin/orphanin FQ-induced stimulation and inhibition of cyclic AMP formation in distinct layers of rat olfactory bulb. AB - 1. We recently reported that nociceptin/orphanin FQ (N/OFQ) inhibited forskolin stimulated adenylyl cyclase activity and increased basal enzyme activity in membranes of the external plexiform layer (EPL) and granule cell layer (GRL), respectively, of the rat main olfactory bulb. In the present study we have characterized the pharmacological profile of the inhibitory and stimulatory responses by examining the effects of various N/OFQ receptor agonists and antagonists. 2. N/OFQ(1 - 13)NH(2) fully mimicked the inhibitory and stimulatory effects of N/OFQ with EC(50) values of 0.9 and 6.5 nM, respectively. N/OFQ(1 - 7) was inactive at concentrations up to 1 microM, whereas Ac-RYYRIK-NH(2) and [Phe(1)Psi(CH(2)NH)Gly(2)]N/OFQ(1 - 13)-NH(2) behaved as partial agonists in eliciting both responses. 3. The nonpeptidyl N/OFQ receptor antagonist J-113397 competitively counteracted the inhibitory and stimulatory effects of N/OFQ with pA(2) values of 8.63 and 8.70, respectively. Similarly, the peptidyl antagonist [Nphe(1)]N/OFQ(1 - 13)NH(2) potently antagonized the two effects with pA(2) values of 8.03 and 8.45, respectively. None of the antagonists per se affected adenylyl cyclase activity. 4. These data show that in distinct layers of rat olfactory bulb both the inhibitory and stimulatory effects of N/OFQ on cyclic AMP formation display pharmacological properties consistent with the involvement of N/OFQ receptors. PMID- 11786500 TI - In vivo evidence for a role of protein kinase C in peripheral nociceptive processing. AB - 1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13 didecanoate (PDD; 0.01, 0.1 or 1 microg), a PKC activator, but not of 4 alpha-PDD (inactive analogue), dose-dependently induced thermal hyperalgesia in rats. This response was not observed at the contralateral hindpaw. Intraplantar injection of PDD (0.01, 0.1 or 1 microg) also induced mechanical allodynia. In mice, injection of PDD (0.1 or 1 microg) into the dorsum of the hindpaw induced a spontaneous licking behaviour. 3. Intraplantar co-injection of chelerythrine (10 or 50 microg), a PKC inhibitor, attenuated the thermal hyperalgesia induced by PDD (0.1 microg) in rats. 4. The second phase of the nociceptive response induced by the injection of formaldehyde (0.92%, 20 microl) into the dorsum of mice hindpaws was inhibited by ipsi-, but not contralateral, pre-treatment with chelerythrine (1 microg). 5. Intraplantar injection of BK (10 microg) induced mechanical allodynia in rats. Ipsi- but not contralateral injection of bisindolylmaleimide I (10 microg), a PKC inhibitor, inhibited BK-induced mechanical allodynia. 6. In conclusion, this study demonstrates that PKC activation at peripheral tissues leads to the development of spontaneous nociceptive response, thermal hyperalgesia and mechanical allodynia. Most importantly, it also gives in vivo evidence that peripheral PKC activation is essential for the full establishment of the nociceptive response induced by two different inflammatory stimuli. PMID- 11786501 TI - Role of the histidine residue at position 105 in the human alpha 5 containing GABA(A) receptor on the affinity and efficacy of benzodiazepine site ligands. AB - 1. A histidine residue in the N-terminal extracellular region of alpha 1,2,3,5 subunits of the human GABA(A) receptor, which is replaced by an arginine in alpha 4 and alpha 6 subunits, is a major determinant for high affinity binding of classical benzodiazepine (BZ)-site ligands. The effect of mutating this histidine at position 105 in the alpha 5 subunit to an arginine (alpha 5H105R) on BZ-site pharmacology has been investigated using radioligand binding on HEK293 and L(tk-) cells and two electrode voltage clamp recording on Xenopus oocytes in which GABA(A) receptors of subtypes alpha 5, alpha 5H105R, alpha 4 and alpha 6 were co expressed with beta 3 gamma 2s. 2. The classical BZs, diazepam and flunitrazepam (full agonists on the alpha 5 receptor) showed negligible affinity and therefore negligible efficacy on alpha 5H105R receptors. The beta-carbolines DMCM and beta CCE (inverse agonists on the alpha 5 receptor) retained some affinity but did not exhibit inverse agonist efficacy at alpha 5H105R receptors. Therefore, the alpha 5H105R mutation confers an alpha 4/alpha 6-like pharmacology to the classical BZs and beta-carbolines. 3. Ro15-4513, flumazenil, bretazenil and FG8094, which share a common imidazobenzodiazepine core structure, retained high affinity and were higher efficacy agonists on alpha 5H105R receptors than would be predicted from an alpha 4/alpha 6 pharmacological profile. This effect was antagonized by DMCM, which competes for the BZ-site and therefore is likely to be mediated via the BZ site. 4. These data indicate that the conserved histidine residue in the alpha subunit is not only a key determinant in the affinity of BZ-site ligands on alpha 5 containing GABA(A) receptors, but also influences ligand efficacy. PMID- 11786502 TI - Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. AB - 1. This study examined the action of gabapentin (gabapentin,1-(aminomethyl) cyclohexane acetic acid (Neurontin) on voltage-gated calcium (Ca(2+)) channel influx recorded in cultured rat dorsal root ganglion (DRG) neurones. 2. Voltage gated Ca(2+) influx was monitored using both fura-2 based fluorescence Ca(2+) imaging and the whole-cell patch clamp technique. 3. Imaging of intracellular Ca(2+) transients revealed that gabapentin inhibited KCl (30 mM)-evoked voltage dependent Ca(2+) influx. Both the duration for 50% of the maximum response (W50) and total Ca(2+) influx were significantly reduced by approximately 25-30% in the presence of gabapentin (25 microM). 4. Gabapentin potently inhibited the peak whole-cell Ca(2+) channel current (I(Ba)) in a dose-dependent manner with an estimated IC(50) value of 167 nM. Block was incomplete and saturated at a maximal concentration of 25 microM. 5. Inhibition was significantly decreased in the presence of the neutral amino acid L-isoleucine (25 microM) but unaffected by application of the GABA(B) antagonist, saclofen (200 microM), suggesting a direct action on the alpha(2)delta subunit of the Ca(2+) channel. 6. Gabapentin inhibition was voltage-dependent, producing an approximately 7 mV hyperpolarizing shift in current voltage properties and reducing a non-inactivating component of whole-cell current activated at relatively depolarized potentials. 7. The use of specific Ca(2+) channel antagonists revealed a mixed pharmacology of the gabapentin-sensitive current (N-, L- and P/Q-type), which is dominated by N-type current. 8. The present study is the first to demonstrate that gabapentin directly mediates inhibition of voltage-gated Ca(2+) influx in DRG neurones, providing a potential means for gabapentin to effectively mediate spinal anti nociception. PMID- 11786503 TI - Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. AB - 1. The effects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. 2. Similar to SP (K(i)=0.13 nM), HEK-1 inhibited in a concentration dependent manner and with high affinity [(3)H]-substance P (SP) binding to human NK(1) receptor (K(i)=0.175 nM) while its affinity for [(125)I]-neurokinin A (NKA) binding at human NK(2) receptor was markedly lower (K(i)=560 nM). 3. In isolated bioassays HEK-1 was a full agonist at tachykinin NK(1), NK(2) and NK(3) receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively. 4. The responses to HEK-1 were antagonized by GR 82334 in RUB (pK(B)=5.6+/-0.07), by nepadutant in RPA (pK(B)=8.6+/-0.04) and by SR 142801 in GPI (pK(B)=9.0+/-0.2) with apparent affinities comparable to that measured against tachykinin NK(1), NK(2) and NK(3) receptor-selective agonists, respectively. 5. Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guinea-pigs (ED(50)=0.1 nmol kg(-1)) and salivary secretion in anaesthetized rats (ED(50)=6 nmol kg(-1)) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK(1) receptor antagonist, SR 140333. 6. We conclude that HEK-1 is a full agonist at tachykinin NK(1), NK(2) and NK(3) receptors, possesses a remarkable selectivity for NK(1) as compared to NK(2) or NK(3) receptors and acts in vivo experiments with potency similar to that of SP. PMID- 11786504 TI - Vasoconstriction is determined by interstitial rather than circulating angiotensin II. AB - 1. We investigated why angiotensin (Ang) I and II induce vasoconstriction with similar potencies, although Ang I-II conversion is limited. 2. Construction of concentration-response curves to Ang I and II in porcine femoral arteries, in the absence or presence of the AT(1) or AT(2) receptor antagonists irbesartan and PD123319, revealed that the approximately 2 fold difference in potency between Ang I and II was not due to stimulation of different AT receptor populations by exogenous and locally generated Ang II. 3. Measurement of Ang I and II and their metabolites at the time of vasoconstriction confirmed that, at equimolar application of Ang I and II, bath fluid Ang II during Ang I was approximately 18 times lower than during Ang II and that Ang II was by far the most important metabolite of Ang I. Tissue Ang II was 2.9+/-1.5% and 12.2+/-2.4% of the corresponding Ang I and II bath fluid levels, and was not affected by irbesartan or PD123319, suggesting that it was located extracellularly. 4. Since approximately 15% of tissue weight consists of interstitial fluid, it can be calculated that interstitial Ang II levels during Ang II resemble bath fluid Ang II levels, whereas during Ang I they are 8.8 - 27 fold higher. Consequently at equimolar application of Ang I and II, the interstitial Ang II levels differ only 2 - 4 fold. 5. Interstitial, rather than circulating Ang II determines vasoconstriction. Arterial Ang I, resulting in high interstitial Ang II levels via its local conversion by ACE, may be of greater physiological importance than arterial Ang II. PMID- 11786505 TI - HMG CoA reductase inhibitors affect the fibrinolytic system of human vascular cells in vitro: a comparative study using different statins. AB - 1. The results of several clinical studies investigating the effect of statin therapy on the fibrinolytic system in vivo are inconclusive. We compared the effect of six different statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin) on components of the fibrinolytic system expressed by human vascular endothelial cells and smooth muscle cells and by the human hepatoma cell line HepG2. 2. All statins used except pravastatin significantly decreased PAI-1 production in human endothelial and smooth muscle cells. This effect was also seen in the presence of IL-1 alpha and TNF-alpha. All statins except pravastatin increased t-PA production in human smooth muscle cells. On a molar basis cerivastatin was the most effective HMG CoA reductase inhibitor used. Only simvastatin and lovastatin increased t-PA production in endothelial cells. The effects on the fibrinolytic system were reversed by mevalonate. Statins decreased mRNA levels for PAI-1 in endothelial and smooth muscle cells and increased mRNA levels for t-PA in smooth muscle cells. Statins did not affect PAI-1 expression in HepG2 cells. Cell viability was not influenced by statins in endothelial cells and HepG2 cells whereas in smooth muscle cells a cytotoxic effect was seen at high concentrations. 3. If the effects on the fibrinolytic system of vascular cells in vitro shown in this study are also operative in vivo one could speculate that by increasing t-PA and decreasing PAI 1 at sites of vascular lesions statins might reduce fibrin formation and thrombus development. Such an effect might contribute to the clinically proven benefits of statin therapy. PMID- 11786506 TI - Cyclic GMP-dependent vasodilatory properties of LASSBio 294 in rat aorta. AB - . The effects of LASSBio 294, a new 3,4-methylenedioxybenzoyl-2-thienylhydrazone, on vascular tonus were investigated in isolated rat aortic rings. 2. LASSBio 294 induced a concentration-dependent relaxation of intact rat aortic rings with an inhibitory concentration (IC(50)) of 74 microM (95% confidence limits: 59 - 92). The mechanical removal of the endothelium abolished this effect. 3. In aortic rings with intact endothelium the effect of 100 microM LASSBio 294 was not altered by the pharmacological inhibition of NOS and cyclo-oxygenase pathways with 500 microM L-NAME and 10 microM indomethacin, respectively. 4. LASSBio 294 (100 microM) was able to relax aortic rings pre-contracted with high extracellular K(+) (KCl 100 mM). 5. The relaxant effect of LASSBio 294 was fully reversed (and prevented) by the addition of 1 microM ODQ (1H (1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one), a selective inhibitor of soluble guanylate cyclase. 6. LASSBio 294 (100 microM) had no direct effect on PDE3 and PDE4 activities, however, it increased by 150% cyclic GMP content in aortic rings pre-treated with 100 microM L-NAME and 10 microM indomethacin, as did 1 microM zaprinast, a selective PDE5 inhibitor. 7. In conclusion, LASSBio 294 induced relaxation of isolated rat aorta probably by directly increasing cyclic GMP content, possibly as a consequence of PDE5 inhibition. PMID- 11786508 TI - The multiple mechanisms by which infection may contribute to atherosclerosis development and course. PMID- 11786509 TI - Vascular dysfunction in hyperglycemia: is protein kinase C the culprit? PMID- 11786510 TI - It's renin in the brain: transgenic animals elucidate the brain renin angiotensin system. PMID- 11786511 TI - Frank-Starling relationship: long on importance, short on mechanism. PMID- 11786512 TI - Calcium and cardiac rhythms: physiological and pathophysiological. PMID- 11786513 TI - cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium. AB - To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (F(c)) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced F(c) in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced F(c) in both groups of animals. 8-Br-cGMP reduced F(c) also in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice. PMID- 11786514 TI - Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: an overview. AB - Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action. PMID- 11786515 TI - Molecular pathogenesis of the antiphospholipid syndrome. AB - The antiphospholipid (aPL) syndrome is an acquired autoimmune disorder of unknown etiology in which patients present with thrombosis together with laboratory evidence for antibodies in blood that recognize anionic phospholipid-protein complexes. The main antigenic target for the aPL antibodies has been identified to be beta(2) glycoprotein I (beta(2)GPI), a phospholipid-binding protein. The high affinity of aPL antibody-beta(2)GPI complex for phospholipid membranes seems to be a critical step in the mechanism of this disease. This review focuses on some of the major mechanisms that have been proposed to explain this disorder. PMID- 11786516 TI - Secretory phospholipase A(2) elicits proinflammatory changes and upregulates the surface expression of fas ligand in monocytic cells: potential relevance for atherogenesis. AB - Type IIA secretory phospholipase A(2) (sPLA(2)) is an acute-phase reactant that plays a role in atherogenesis and is expressed in atherosclerotic arterial walls displaying inflammatory features. This generates a relevant question addressing the biological effects of this enzyme on monocytic cells, in view of the role of these cells in the inflammatory process associated with atherosclerosis. sPLA(2) produced a mild activation of the p42 mitogen-activated protein module of the mitogen-activated protein kinase (MAPK) cascade and a prominent activation of c Jun N-terminal kinase in THP-1 monocytes. This activation showed both an early and a late peak, different from that elicited by tumor necrosis factor-alpha (TNF alpha), which only showed the first peak. This was accompanied by activation of arachidonate metabolism, as judged from both the activation of the cytosolic phospholipase A(2) (cPLA(2)) and the induction of cyclooxygenase-2 (COX-2) expression. sPLA(2) also elicited the production of monocyte chemoattractant protein-1 (MCP-1) and showed a synergistic effect with TNF-alpha on both COX-2 induction and MCP-1 production. sPLA(2) upregulated the expression of Fas ligand at the cell surface, but it did not influence Fas expression nor cell survival of monocytes. In summary, these data indicate that some of the atherogenic effects of sPLA(2) can be exerted by engagement of an sPLA(2)-binding structure on monocytic cells, most probably the M-type receptor for sPLA(2), which produces the activation of the MAPK cascade, induces a proinflammatory phenotype, and upregulates the cell surface expression of Fas ligand. PMID- 11786517 TI - Vascular origin of a soluble truncated form of the hepatocyte growth factor receptor (c-met). AB - Hepatocyte growth factor (scatter factor) is an angiogenic growth factor that binds to its cellular transmembrane receptor, c-met. Both HGF and c-met are expressed by vascular smooth muscle and endothelial cells, where HGF may exert autocrine and paracrine effects. We have found that human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) release a soluble, truncated form of c-met. Receptor shedding was induced by treatment of the cells with phorbol 12-myristate 13-acetate (PMA) and by the ligand, HGF. Shedding was inhibited by cycloheximide, a metalloproteinase inhibitor, and protein kinase C inhibitors. The soluble form of c-met was able to bind HGF, although with reduced affinity (K(d) approximately 10 nmol/L) compared with the membrane bound receptor. Conditioned medium containing soluble c-met inhibited the induction of Akt phosphorylation by HGF in HUVECs. The soluble truncated form of c-met was detectable in the plasma of 5 healthy volunteers. The shedding of c met may represent a novel mechanism for regulating the mitogenic, motogenic, and morphogenic effects of hepatocyte growth factor. PMID- 11786518 TI - Destabilization of AT(1) receptor mRNA by calreticulin. AB - AT(1) receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT(1) receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT(1) receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT(1) receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT(1) receptor mRNA decay in vascular smooth muscle cells. A cognate mRNA region within the 3' untranslated region at bases 2175 to 2195 governs the inducible decay of the AT(1) receptor mRNA. Sequential protein purifications led to the discovery of a novel mRNA binding protein, calreticulin, which mediates destabilization of the AT(1) receptor mRNA. Angiotensin II-caused phosphorylation of calreticulin enables binding of calreticulin to the AT(1) receptor mRNA at bases 2175 to 2195 and propagates calreticulin-induced acceleration of AT(1) receptor mRNA decay. Thus, a novel mRNA binding protein, calreticulin, is discovered, which causes AT(1) receptor mRNA degradation via binding to a distinct mRNA region in the 3' untranslated region. These findings display a novel mechanism of posttranscriptional mRNA processing. PMID- 11786519 TI - Myofilament calcium sensitivity in skinned rat cardiac trabeculae: role of interfilament spacing. AB - The increase in myofilament Ca(2+) responsiveness on an increase in sarcomere length (SL) is, in part, the cellular basis for Frank-Starling's law of the heart. It has been suggested that a decrease in myofilament lattice spacing (LS) in response to an increase in SL underlies this phenomenon. This hypothesis is supported by previous studies in which reduced muscle width induced by osmotic compression was associated with an increase in Ca(2+) sensitivity, mimicking those changes observed with an increase in SL. To evaluate this hypothesis, we directly measured LS by synchrotron x-ray diffraction as function of SL in skinned rat cardiac trabeculae bathed in 0% to 6% dextran solutions (MW 413 000). We found that EC(50), [Ca(2+)] at which force is half-maximal, at SL between 1.95 and 2.25 microm did not vary in proportion to LS when 3% or 6% dextran solutions were applied. We also found that moderate compression (1% dextran) of skinned trabeculae at SL=2.02 microm reduced LS (LS=42.29+/-0.14 nm) to match that of uncompressed fibers at a long SL (SL=2.19 microm; LS=42.28+/-0.15 nm). Whereas increasing SL from 2.02 to 2.19 microm significantly increased Ca(2+) sensitivity as indexed by the EC(50) parameter (2.87+/-0.11 micromol/L to 2.52+/-0.12 micromol/L), similar reduction in myofilament lattice spacing achieved by compression with 1% dextran did not alter Ca(2+) sensitivity (2.87+/-0.10 micromol/L) at the short SL. We conclude that alterations in myofilament lattice spacing may not be the mechanism that underlies the sarcomere length-induced alteration of calcium sensitivity in skinned myocardium. PMID- 11786520 TI - Alterations of myocardial dynamic stiffness implicating abnormal crossbridge function in human mitral regurgitation heart failure. AB - Mitral regurgitation (MR) causes ventricular dilation, a blunted myocardial force frequency relation, and increased crossbridge force-time integral (FTI). The mechanism of FTI increase was investigated using sinusoidal length perturbation analysis to compare crossbridge function in skinned left ventricular (LV) epicardial muscle strips from 5 MR and 5 nonfailing (NF) control hearts. Myocardial dynamic stiffness was modeled as 3 parallel viscoelastic processes. Two processes characterize intermediate crossbridge cycle transitions, B (work producing) and C (work absorbing) with Q(10)s of 4 to 5. No significant differences in moduli or kinetic constants of these processes were observed between MR and NF. The third process, A, characterizes a nonenzymatic (Q(10)=0.9) work-absorbing viscoelasticity, whose modulus increases sigmoidally with [Ca(2+)]. Effects of temperature, crossbridge inhibition, or variation in [MgATP] support associating the calcium-dependent portion of A with the structural "backbone" of the myosin crossbridge. Extension of the conventional sinusoidal length perturbation analysis allowed using the A modulus to index the lifetime of the prerigor, AMADP crossbridge. This index was 75% greater in MR than in NF (P=0.02), suggesting a mechanism for the previously observed increase in crossbridge FTI. Notably, the A-process modulus was inversely correlated (r(2)=0.84, P=0.03) with in vivo LV ejection fraction in MR patients. The longer prerigor dwell time in MR may be clinically relevant not only for its potential role as a compensatory mechanism (increased economy of tension maintenance and increased resistance to ventricular dilation) but also for a potentially deleterious effect (reduced elastance and ejection fraction). PMID- 11786521 TI - beta-Adrenergic stimulation modulates ryanodine receptor Ca(2+) release during diastolic depolarization to accelerate pacemaker activity in rabbit sinoatrial nodal cells. AB - It has long been recognized that activation of sympathetic beta-adrenoceptors (beta-ARs) increases the spontaneous beating rate of sinoatrial nodal cells (SANCs); however, the specific links between stimulation of beta-ARs and the resultant increase in firing rate remain an enigma. In the present study, we show that the positive chronotropic effect of beta-AR stimulation is critically dependent on localized subsarcolemmal ryanodine receptor (RyR) Ca(2+) releases during diastolic depolarization (CRDD). Specifically, isoproterenol (ISO; 0.1 micromol/L) induces a 3-fold increase in the number of CRDDs per cycle; a shift to higher CRDD amplitudes (from 2.00+/-0.04 to 2.17+/-0.03 F/F(0); P<0.05 [F and F(0) refer to peak and minimal fluorescence]); and an increase in spatial width (from 3.80+/-0.44 to 5.45+/-0.47 microm; P<0.05). The net effect results in an augmentation of the amplitude of the local preaction potential subsarcolemmal Ca(2+) transient that, in turn, accelerates the diastolic depolarization rate, leading to an increase in SANC firing rate. When RyRs are disabled by ryanodine, beta-AR stimulation fails to amplify subsarcolemmal Ca(2+) releases, fails to augment the diastolic depolarization rate, and fails to increase the SANC firing rate, despite preserved beta-AR stimulation-induced augmentation of L-type Ca(2+) current amplitude. Thus, the RyR Ca(2+) release acts as a switchboard to link beta-AR stimulation to an increase in SANC firing rate: recruitment of additional localized CRDDs and partial synchronization of their occurrence by beta-AR stimulation lead to an increase in the heart rate. PMID- 11786522 TI - The brain renin-angiotensin system in transgenic mice carrying a highly regulated human renin transgene. AB - We previously reported the generation of 2 novel transgenic mouse models containing the human renin (hREN) gene encoded on P1 artificial chromosomes (PAC) containing large amounts of 5'-flanking DNA. These mice exhibit a very narrow tissue-specific expression profile and exhibit tightly regulated expression in kidney in response to physiological cues. In brain, transcription of hREN occurs from an alternative upstream promoter, causing translation to initiate within exon-II and potentially generating an intracellular form of active renin. Double transgenic mice containing a PAC transgene and the human angiotensinogen (hAGT) gene (P+/A+) are moderately hypertensive. We tested whether increased RAS activity in the brain contributes to the mechanism of hypertension in P+/A+ double transgenic mice. Expression of hREN mRNA in brain was confirmed in 4 independent PAC transgenic lines and utilization of the alternative transcription start site in brain was confirmed in each line. Human REN immunostaining was observed in the dorsal cochlear nucleus, hypothalamus, and cortex. P+/A+ mice exhibited a greater fall in mean arterial pressure after intracerebroventricular injection of losartan than controls. P+/A+ mice exhibited a greater drop in arterial pressure after intravenous injection of a vasopressin V(1) receptor antagonist, and an equivalent drop in arterial pressure after intravenous injection of a ganglion blocker compared with controls. These results support the hypothesis that renin is endogenously expressed in the brain and suggest that increased brain RAS activity may contribute to the maintenance of moderate hypertension in P+/A+ transgenic mice at least in part by a vasopressin-dependent mechanism. PMID- 11786523 TI - Mice lacking endothelial angiotensin-converting enzyme have a normal blood pressure. AB - To test the hypothesis that local vascular production of angiotensin II is necessary for the normal regulation of blood pressure, we engineered a new line of genetically altered mice that lack endothelial angiotensin-converting enzyme (ACE). This was accomplished using a novel strategy of targeted homologous recombination to separate the transcriptional control of somatic ACE from its endogenous promoter and to substitute control to the albumin promoter. These new mice, termed ACE.3, do not produce ACE within the lung, the aorta, or any vascular structure. ACE activity within the kidney is only about 14% that of wild type mice and is limited to tubular epithelium. In contrast, hepatic ACE expression in ACE.3 mice is about 87-fold that of wild-type. The blood pressure, plasma angiotensin II levels, response to ACE inhibitors, and renal function of ACE.3(-/-) mice are indistinguishable from littermate wild-type mice. These data show that, under basal conditions, the normal regulation of blood pressure and renal function is possible in a mouse devoid of endothelial ACE. PMID- 11786525 TI - Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation. AB - The aim of the present study was to investigate the effects of the novel poly(ADP ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2 yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34 treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction. PMID- 11786524 TI - Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction. AB - Nitric oxide (NO), a potent regulator of myocardial contractility, has been implicated in the development of heart failure; however, no study exists describing the relation between expression of inducible nitric oxide synthase (iNOS), formation of NO in vivo, and cardiac contractility. We have therefore generated transgenic (TG) mice overexpressing iNOS under the cardiospecific alpha myosin heavy chain (alpha-MHC) promoter. In vitro, iNOS activity in hearts of two transgenic lines was 260- to 400-fold above controls (wild type [WT]), but TG mice were viable and appeared normal. Ventricular mass/body weight ratio did not differ; heart rate and cardiac output as well as mean arterial blood pressure were decreased by 10%. NO(x) levels of hearts and blood of TG mice were 2.5- and 2-fold above WT controls, respectively. In the isolated heart, release of the NO oxidation products nitrate and nitrite, an index of in vivo NOS activity, was 40 fold over WT. However, cardiac hemodynamics and levels of ATP and phosphocreatine were unaltered. The high iNOS activity was associated with reduced cardiac L arginine in TG hearts to only 15% of the WT, indicating limited substrate availability, whereas L-citrulline was 20-fold elevated. Our findings demonstrate that the heart can tolerate high levels of iNOS activity without detrimental functional consequences. The concept that iNOS-derived NO is the triggering factor in the pathomechanism leading to heart failure therefore needs to be reevaluated. PMID- 11786526 TI - Inhibition of protein kinase Cbeta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. AB - The bioavailability of nitric oxide is decreased in animal models and humans with diabetes mellitus. Hyperglycemia, in particular, attenuates endothelium-dependent vasodilation in healthy subjects. In vitro and in vivo animal studies implicate activation of protein kinase Cbeta as an important mechanism whereby hyperglycemia decreases endothelium-derived nitric oxide. Accordingly, this study tested the hypothesis that inhibition of protein kinase Cbeta would prevent impairment of endothelium-dependent vasodilation in healthy humans exposed to hyperglycemia. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy subjects were treated with an orally active, selective, protein kinase Cbeta inhibitor, LY333531, or matching placebo once a day for 7 days before vascular function testing. Forearm blood flow was measured using venous-occlusion, strain-gauge plethysmography. Endothelium-dependent vasodilation was measured via incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/min) during euglycemia and after 6 hours of hyperglycemic clamp. The forearm blood flow dose-response curve to methacholine was significantly attenuated by hyperglycemia after placebo treatment (P=0.009 by ANOVA, euglycemia versus hyperglycemia) but not after treatment with LY333531. Inhibition of protein kinase Cbeta prevents the reduction in endothelium-dependent vasodilation induced by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia impairs endothelial function, in part, via protein kinase Cbeta activation. PMID- 11786527 TI - Influence of Helicobacter pylori infection during atherogenesis in vivo in mice. AB - Inflammatory diseases may have a role in the pathogenesis of atherosclerosis. Several epidemiological and clinical studies have explored the possible association between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease. The contradictory results of these studies have fueled a debate regarding the link between H pylori infection and atherogenesis. This study tested the hypothesis that H pylori infection might influence atherosclerosis in vivo in mice. Male wild-type C57/Bl6 mice and LDL receptor deficient congenic mice were randomly assigned for infection with H pylori. All animals were fed a high-cholesterol diet (1.25%) for 6 or 12 weeks. At autopsy, we compared aortic atherosclerotic lesion formation and lipid deposition. H pylori infection influenced neither the progression of atherosclerotic lesions nor lipid deposition. Moreover, the cellularity of atherosclerotic lesions (macrophages and T cells) did not differ between mice infected or not infected with H pylori. This in vivo study performed in a mouse model of atherosclerosis revealed no indication that H pylori infection might contribute to the development of atherosclerotic lesion formation. The full text of this article is available at http://www.circresaha.org. PMID- 11786528 TI - FGF2 signaling is required for the development of neuronal circuits regulating blood pressure. AB - Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy. Mice lacking a functional FGF2 gene (FGF2(-/-)) are hypotensive, but the primary physiological role of FGF2 in cardiovascular homeostasis remained unknown. Using a chicken FGF2 (cFGF2) transgene under control of the Wnt-1 promotor, we selectively re-expressed FGF2 in the developing nervous system of FGF2(-/-) (transgenic FGF2 mutant) embryos. Expression of the cFGF2 transgene in the developing nervous system, including its autonomic region, was limited to the period between embryonic day 9.5 and 14.5. Significantly, no FGF2 re-expression was detected in developing heart and blood vessels. Pharmacological analysis revealed a normalization of the blood pressure response to isoproterenol-induced vasodilation in adult transgenic FGF2 mutant mice. In addition, the hypotensive phenotype was rescued in 1 line (of 2) transgenic FGF2 mutant adult mice having expressed higher levels of cFGF2 proteins during nervous system development. These genetic studies indicate that FGF2 signaling is essential for complete development of the neural circuitry required for central regulation of blood pressure, whereas it appears dispensable for blood pressure control in the healthy adult. The full text of this article is available at http://www.circresaha.org. PMID- 11786529 TI - Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. AB - Brugada syndrome is an inherited cardiac disorder caused by mutations in the cardiac sodium channel gene, SCN5A, that leads to ventricular fibrillation and sudden death. This study reports the changes in functional expression and cellular localization of an SCN5A double mutant (R1232W/T1620M) recently discovered in patients with Brugada syndrome. Mutant and wild-type (WT) human heart sodium channels (hNa(v)1.5) were expressed in tsA201 cells in the presence of the beta(1)-auxiliary subunit. Patch-clamp experiments in whole-cell configuration were conducted to assess functional expression. Immunohistochemistry and confocal microscopy were used to determine the spatial distribution of either WT or mutant cardiac sodium channels. The results show an abolition of functional sodium channel expression of the hNa(v)1.5/R1232W/T1620M mutant in the tsA201 cells. A conservative positively charged mutant, hNa(v)1.5/R1232K/T1620M, produced functional channels. Immunofluorescent staining showed that the FLAG-tagged hNa(v)1.5/WT transfected into tsA201 cells was localized on the cell surface, whereas the FLAG-tagged hNa(v)1.5/R1232W/T1620M mutant was colocalized with calnexin within the endoplasmic reticulum (ER). These results indicate that a positively charged arginine or lysine residue at position 1232 in the double mutant is required for the proper transport and functional expression of the hNa(v)1.5 protein. These results support the concept that loss of function of the cardiac Na(+) channel is responsible for the Brugada syndrome. The full text of this article is available at http://www.circresaha.org. PMID- 11786530 TI - Structure and mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase. An enzyme in the mevalonate-independent isoprenoid biosynthetic pathway. AB - The enzyme 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2 phosphate (CDP-ME2P) to MECDP, a highly unusual cyclodiphosphate-containing intermediate on the mevalonate-independent pathway to isopentenyl diphosphate and dimethylallyl diphosphate. We now report two x-ray crystal structures of MECDP synthase refined to 2.8-A resolution. The first structure contains a bound Mn(2+) cation, and the second structure contains CMP, MECDP, and Mn(2+). The protein adopts a homotrimeric quaternary structure built around a central hydrophobic cavity and three externally facing active sites. Each of these active sites is located between two adjacent monomers. A tetrahedrally arranged transition metal binding site, potentially occupied by Mn(2+), sits at the base of the active site cleft. A phosphate oxygen of MECDP and the side chains of Asp(8), His(10), and His(42) occupy the metal ion coordination sphere. These structures reveal for the first time the structural determinants underlying substrate, product, and Mn(2+) recognition and the likely catalytic mechanism accompanying the biosynthesis of the cyclodiphosphate-containing isoprenoid precursor, MECDP. PMID- 11786531 TI - Novel role of Janus kinase 1 in the regulation of oncostatin M receptor surface expression. AB - The oncostatin M receptor (OSMR) is part of a heterodimeric receptor complex that mediates signal transduction of the pleiotropic cytokine OSM via a signaling pathway involving Janus kinases (Jaks) and transcription factors of the signal transducers and activators of transcription (STAT) family. Upon heterologous expression of the OSMR in several cell lines, we observed that its surface expression was significantly enhanced by coexpression of the Janus kinases Jak1, Jak2, and Tyk2 but not Jak3. Chimeric receptors consisting of the extracellular region of the interleukin-5 receptor beta chain and the transmembrane and intracellular part of the OSMR were similarly up-regulated on the plasma membrane when Jak1 was coexpressed. The overall expression level of these constructs did not change significantly, but Jak1 coexpression increased the amount of endoglycosidase H-resistant, fully processed OSMR chimeras. Using mutated receptor and Jak1 constructs, we were able to demonstrate that association of Jak1 with the membrane proximal region of the receptor, but not its kinase activity, is necessary for this effect. Moreover, deletion of the OSMR box1/2 region also resulted in an improved surface expression indicating that this region may contain a signal preventing efficient receptor surface expression in the absence of associated Jaks. Finally we demonstrate that in Jak1-deficient cells, the endogenous OSMR is significantly down-regulated, an effect that can be reversed by transient expression of Jak1 in these cells. PMID- 11786533 TI - Regulation of the murine Nfatc1 gene by NFATc2. AB - NFAT proteins play a key role in the inducible expression of cytokine genes in T lymphocytes. NFATc1 and NFATc2 are the predominant NFAT family members in the peripheral immune system. NFATc2 is found abundantly in the cytoplasm of resting T cells, whereas Nfatc1 expression is induced during T cell activation. To investigate Nfatc1 regulation, we characterized the structure of the murine Nfatc1 gene and its 5'-flanking region. A 290-bp sequence proximal to the transcription start site is highly conserved between mouse and human and possesses both basal and inducible promoter activities. Multiple binding sites for transcription factors were identified within this region, including a consensus NFAT-binding site. This promoter segment was cyclosporin A-sensitive, and mutation of the NFAT site abrogated inducible promoter activity and inhibited formation of an inducible DNA x protein complex containing NFATc2 in primary T cells. Overexpression of NFATc2 increased inducible Nfatc1 promoter activity, whereas this inducibility was attenuated in NFATc2(-/-) splenocytes. This study suggests that pre-existing NFATc2 contributes to the subsequent induction of Nfatc1 during T cell activation. PMID- 11786532 TI - A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production. AB - Endotoxin (lipopolysaccharide, LPS) is a component of the outer membrane of Gram negative bacteria and promotes the activation of macrophages and microglia. Although these cells are highly LPS-responsive, they serve unique tissue-specific functions and exhibit different LPS sensitivities. Accordingly, it was of interest to evaluate whether these biological differences reside in variations within LPS signaling pathways between these two cell types. Because the mitogen activated protein kinases ERK-1 and ERK-2 have been implicated in the control of many immune responses, we tested the concept that they are a key indicator for differences in cellular LPS sensitivity. We observed that murine RAW 264.7 macrophages and murine BV-2 microglial cells both respond to LPS by exhibiting increased IkappaBalpha degradation, enhanced NF-kappaB DNA binding activity, and elevated nitric oxide and interleukin-1beta production. Although LPS potently stimulates ERK activation in RAW 264.7 macrophages, it does not activate ERK-1/-2 in BV-2 microglia. Moreover, antagonism of the MEK/ERK pathway potentiates LPS stimulated nitric oxide production, suggesting that LPS-stimulated ERK activation can exert inhibitory effects in macrophage-like cells. These data support the idea that ERK activation is not a required function of LPS-mediated signaling events and illustrate that alternative/additional pathways for LPS action exist in these cell types. PMID- 11786534 TI - Gene transfection of H25A mutant heme oxygenase-1 protects cells against hydroperoxide-induced cytotoxicity. AB - Heme oxygenase (HO)-1 is a stress-inducible enzyme protecting cells against oxidative stress, and mechanisms have been considered to depend exclusively on its enzyme activity. This study aimed to examine if the protein lacking catalytic activities could also display such resistance against oxidative stress. Stable transfectants of rat wild type HO-1 cDNA (HO-1-U937) and those of its H25A mutant gene (mHO-1-U937) were established using human monoblastic lymphoma cell U937. HO 1-U937 and mHO-1-U937 used in the study exhibited similar levels of the protein expression, while only the former increased enzyme activities. HO-1- and mHO-1 U937 cells became more and less sensitive to H(2)O(2) than mock transfectants, respectively; such distinct susceptibility between the cells was ascribable to differences in the capacity to scavenge H(2)O(2) through catalase and to execute iron-mediated oxidant propagation. On the other hand, both cell lines exhibited greater resistance to tert-butyl hydroperoxide than mock transfectants. The resistance of HO-1-U937 to hydroperoxides appeared to result from antioxidant properties of bilirubin, an HO-derived product, while that of mHO-1-U937 was ascribable to increased contents of catalase and glutathione. These results provided evidence that gene transfection of the activity-lacking mutant HO-1 protects cells against oxidative stress through multiple mechanisms involving up regulation of catalase and glutathione contents. PMID- 11786535 TI - Regulation of synaptophysin degradation by mammalian homologues of seven in absentia. AB - Synaptophysin is an integral membrane protein of synaptic vesicles characterized by four transmembrane domains with both termini facing the cytoplasm. Although synaptophysin has been implicated in neurotransmitter release, and decreased synaptophysin levels have been associated with several neurodegenerative diseases, the molecular mechanism that regulates the degradation of synaptophysin remains unsolved. Using the cytoplasmic C terminus of synaptophysin as bait in a yeast two-hybrid screen, we identified two synaptophysin-binding proteins, Siah 1A and Siah-2, which are rat homologues of Drosophila Seven in Absentia. We demonstrated that Siah-1A and Siah-2 associate with synaptophysin both in vitro and in vivo and defined the binding domains of synaptophysin and Siah that mediate their association. Siah proteins exist in both cytosolic and membrane associated pools and co-localize with synaptophysin on synaptic vesicles and early endosomes. In addition, Siah proteins interact specifically with the brain enriched E2 ubiquitin-conjugating enzyme UbcH8 and facilitate the ubiquitination of synaptophysin. Furthermore, overexpression of Siah proteins promotes the degradation of synaptophysin via the ubiquitin-proteasome pathway. Our findings indicate that Siah proteins function as E3 ubiquitin-protein ligases to regulate the ubiquitination and degradation of synaptophysin. PMID- 11786536 TI - A novel mechanism by which interferon-gamma can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor alpha -2 and their rapid mobilization by interferon-gamma. AB - Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor alpha-1 chain (IL-13Ralpha1) binds IL-13 with low affinity, but does not signal. However, when IL-13Ralpha1 combines with IL-4 receptor alpha (IL-4Ralpha), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13Ralpha2 alone binds IL-13 with high affinity, but does not signal and has been postulated to be a decoy receptor. Herein, we investigated the cellular localization of IL-13Ralpha2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13Ralpha2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-gamma. Up-regulation of IL-13Ralpha2 surface expression in response to IFN-gamma was rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13Ralpha2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-gamma can regulate IL-13 responses. PMID- 11786537 TI - Specificity determinants in MAPK signaling to transcription factors. AB - One critical component in determining the specificity, fidelity, and efficiency of MAPK substrate phosphorylation is the presence of distinct docking domains in the substrate proteins. These docking domains are found in a range of substrates, including the transcription factors myocyte enhancer factor-2A and SAP-1. However, the sequences of these motifs differ, as does their targeting preferences by MAPKs, with SAP-1 being targeted by both the ERK and p38 isoforms, whereas myocyte enhancer factor-2A is targeted only by certain members of the p38 subfamily. Here, we have investigated the specificity determinants within these motifs and generated a model for how specificity is generated. We demonstrate that residues throughout the docking domains play important roles in the recognition process. However, residues located at different positions are important for discriminating between ERK and p38 MAPKs. Furthermore, the docking domains can be further subdivided into submotifs, which are differentially required for phosphorylation by ERK or p38 MAPKs. We have used loss- and gain-of function mutagenesis to identify residues that discriminate between ERK and p38 MAPKs, residues that act to promote suboptimal interactions, and regions that are differentially required depending on the kinase involved. A model is proposed to explain how specificity is generated within these short docking domains. PMID- 11786538 TI - Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein. AB - Rab4 and Rab11 are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts specifically with the GTP-bound conformation of Rab4, and subsequent work has shown that it also interacts strongly with Rab11. We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested. It colocalizes with early endosomal markers including Rab4 and Rab11 as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment. Furthermore, expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family. PMID- 11786539 TI - The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases. AB - Post-translational modifications of GTPases from the Ras superfamily enable them to associate with membrane compartments where they exert their biological activities. However, no protein acting like Rho and Rab dissociation inhibitor (GDI) that regulate the membrane association of Rho and Rab GTPases has been described for Ras and closely related proteins. We report here that the delta subunit of retinal rod phosphodiesterase (PDEdelta) is able to interact with prenylated Ras and Rap proteins, and to solubilize them from membranes, independently of their nucleotide-bound (GDP or GTP) state. We show that PDEdelta exhibits striking structural similarities with RhoGDI, namely conservation of the Ig-like fold and presence of a series of hydrophobic residues which could act as in RhoGDI to sequester the prenyl group of its target proteins, thereby providing structural support for the biochemical activity of PDEdelta. We observe that the overexpression of PDEdelta interferes with Ras trafficking and propose that it may play a role in the process that delivers prenylated proteins from endomembranes, once they have undergone proteolysis and carboxymethylation, to the structures that ensure trafficking to their respective resident compartments. PMID- 11786540 TI - Modifications in the C terminus of the synaptosome-associated protein of 25 kDa (SNAP-25) and in the complementary region of synaptobrevin affect the final steps of exocytosis. AB - Fusion proteins made of green fluorescent protein coupled to SNAP-25 or synaptobrevin were overexpressed in bovine chromaffin cells in order to study the role of critical protein domains in exocytosis. Point mutations in the C-terminal domain of SNAP-25 (K201E and L203E) produced a marked inhibition of secretion, whereas single (Q174K, Q53K) and double mutants (Q174K/Q53K) of amino acids from the so-called zero layer only produced a moderate alteration in secretion. The importance of the SNAP-25 C-terminal domain in exocytosis was also confirmed by the similar effect on secretion of mutations in analogous residues of synaptobrevin (A82D, L84E). The effects on the initial rate and magnitude of secretion correlated with the alteration of single vesicle fusion kinetics since the amperometric spikes from cells expressing SNAP-25 L203E and K201E and synaptobrevin A82D and L84E mutants had lower amplitudes and larger half-width values than the ones from controls, suggesting slower neurotransmitter release kinetics than that found in cells expressing the wild-type proteins or zero layer mutants of SNAP-25. We conclude that a small domain of the SNAP-25 C terminus and its counterpart in synaptobrevin play an essential role in the final membrane fusion step of exocytosis. PMID- 11786541 TI - 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. AB - Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of tissues, readily undergoes dehydration to yield the cyclopentenone-type PGs of the J(2) series, such as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), which have been suggested to exert anti-inflammatory effects in vivo. Meanwhile, the mechanism of these effects is not well understood and the natural site and the extent of its production in vivo remain unclear. In the present study, we raised a monoclonal antibody specific to 15d-PGJ(2) and determined its production in inflammation-related events. The monoclonal antibody (mAb11G2) was raised against the 15d-PGJ(2)-keyhole limpet hemocyanin conjugate and was found to recognize free 15d-PGJ(2) specifically. The presence of 15d-PGJ(2) in vivo was immunohistochemically verified in the cytoplasm of most of the foamy macrophages in human atherosclerotic plaques. In addition, the immunostaining of lipopolysaccharide-stimulated RAW264.7 macrophages with mAb11G2 demonstrated an enhanced intracellular accumulation of 15d-PGJ(2), suggesting that the PGD(2) metabolic pathway, generating the anti-inflammatory PGs, is indeed utilized in the cells during inflammation. The activation of macrophages also resulted in the extracellular production of PGD(2), which was associated with a significant increase in the extracellular 15d-PGJ(2) levels, and the extracellular 15d-PGJ(2) production was reproduced by incubating PGD(2) in a cell-free medium and in phosphate-buffered saline. Moreover, using a chiral high performance liquid chromatography method for separation of PGD(2) metabolites, we established a novel metabolic pathway, in which PGD(2) is converted to 15d-PGJ(2) via an albumin-independent mechanism. PMID- 11786542 TI - Constitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2. AB - Polycystin-1 (PC1), a 4,303-amino acid integral membrane protein of unknown function, interacts with polycystin-2 (PC2), a 968-amino acid alpha-type channel subunit. Mutations in their respective genes cause autosomal dominant polycystic kidney disease. Using a novel heterologous expression system and Ca(2+) and K(+) channels as functional biosensors, we found that full-length PC1 functioned as a constitutive activator of G(i/o)-type but not G(q)-type G-proteins and modulated the activity of Ca(2+) and K(+) channels via the release of Gbetagamma subunits. PC1 lacking the N-terminal 1811 residues replicated the effects of full-length PC1. These effects were independent of regulators of G-protein signaling proteins and were lost in PC1 mutants lacking a putative G-protein binding site. Co expression with full-length PC2, but not a C-terminal truncation mutant, abrogated the effects of PC1. Our data provide the first experimental evidence that full-length PC1 acts as an untraditional G-protein-coupled receptor, activity of which is physically regulated by PC2. Thus, our study strongly suggests that mutations in PC1 or PC2 that distort the polycystin complex would initiate abnormal G-protein signaling in autosomal dominant polycystic kidney disease. PMID- 11786543 TI - The E2F family of transcription factors from Arabidopsis thaliana. Novel and conserved components of the retinoblastoma/E2F pathway in plants. AB - The E2F transcription factors are key components of the cyclin D/retinoblastoma/E2F pathway. Here we demonstrate that Arabidopsis thaliana contains six functional AtE2F genes that are all expressed in cell suspension culture but show different patterns of expression during cell cycle progression. According to their structural and functional features, the six AtE2Fs can be divided into two distinct groups; although the three members of the first group, AtE2Fa, AtE2Fb and AtE2Fc, possess all the conserved domains found in other plant and animal E2Fs, the remaining AtE2Fs are novel proteins, which reveal a duplication of the DNA binding domain but lack any other conserved region. Furthermore, the AtE2Fs of the first group are functional transcription factors that in association with AtDP proteins can recognize specifically an E2F cis element and can transactivate an E2F-responsive reporter gene in plant cells. In contrast, the AtE2Fs of the second group can bind specifically the E2F site without interacting with DP partners but cannot activate gene expression and, instead, are able to inhibit E2F-dependent activation of gene expression in Arabidopsis cells. These findings suggest distinctive roles for the plant E2F proteins and point to a complex concerted regulation of E2F-dependent gene expression in plant cells. PMID- 11786544 TI - Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy. Preservation of systolic function. AB - Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that transduces hypertrophic stimuli to regulate transcriptional control of myocyte transformation. It is not known whether overexpression of MCIP1, a recently described endogenous inhibitor of calcineurin, impacts the hypertrophic response to pathophysiologically relevant pressure overload. Further, the functional consequences of calcineurin inhibition by MCIP1 under conditions of hemodynamic stress are unknown. Transgenic mice expressing a human cDNA encoding hMCIP1 in the myocardium were subjected to thoracic aortic banding. Transgenic mice and wild type littermates tolerated pressure overload equally well. Wild type mice developed left ventricular hypertrophy, but the hypertrophic response in transgenics was significantly blunted. An isoform of MCIP1 transcript was up regulated by pressure stress, whereas MCIP2 transcript was not. Expression patterns of fetal genes were differentially regulated in banded MCIP1 hearts compared with wild type. Echocardiography performed at 3 weeks and 3 months revealed preservation of both left ventricular size and systolic function in banded MCIP1 mice despite the attenuated hypertrophic response. These data demonstrate attenuation of hypertrophic transformation when calcineurin is inhibited by MCIP1. Further, these data suggest that activation of hypertrophic marker genes may not be directly dependent on calcineurin activity. Finally, they demonstrate that ventricular performance is preserved despite attenuation of compensatory hypertrophy. PMID- 11786545 TI - SH2-Bbeta is a Rac-binding protein that regulates cell motility. AB - The Src homology 2 (SH2) domain-containing protein SH2-Bbeta binds to and is a substrate of the growth hormone (GH) and cytokine receptor-associated tyrosine kinase JAK2. SH2-Bbeta also binds, via its SH2 domain, to multiple activated growth factor receptor tyrosine kinases. We have previously implicated SH2-Bbeta in GH and platelet-derived growth factor regulation of the actin cytoskeleton. We extend these findings by establishing a potentiating effect of SH2-Bbeta on GH dependent cell motility and defining regions of SH2-Bbeta required for this potentiation. Time-lapse video microscopy, phagokinetic, and/or wounding assays demonstrate reduced movement of cells overexpressing SH2-Bbeta lacking an intact SH2 domain because of a point mutation or a C-terminal truncation. An N-terminal proline-rich domain (amino acids 85-106) of SH2-Bbeta is required for inhibition of cellular motility by SH2 domain-deficient mutants. Co-immunoprecipitation experiments indicate that Rac binds to this domain. GH is shown to activate endogenous Rac, and dominant negative mutants of SH2-Bbeta are shown to inhibit membrane ruffling induced by constitutively active Rac. These findings suggest that SH2-Bbeta is an adapter protein that facilitates actin rearrangement and cellular motility by recruiting Rac and potentially Rac-regulating, Rac effector, or other actin-regulating proteins to activated cytokine (e.g. GH) and growth factor receptors. PMID- 11786546 TI - Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling. AB - The interferon-alpha (IFNalpha) receptor consists of two subunits, the IFNalpha receptor 1 (IFNaR1) and 2 (IFNaR2) chains. Following ligand binding, IFNaR1 is phosphorylated on tyrosine 466, and this site recruits Stat2 via its SH2 domain. In contrast, IFNaR2 binds Stat2 constitutively. In this study we have characterized the Stat2-IFNaR2 interaction and examined its role in IFNalpha signaling. Stat2 binds the major IFNaR2 protein but not a variant containing a shorter cytoplasmic domain. The interaction does not require a STAT SH2 domain. Both tyrosine-phosphorylated and non-phosphorylated Stat2 bind IFNaR2 in vitro; however, relatively little phosphorylated Stat2 associates with IFNaR2 in vivo. In vitro binding assays defined IFNaR2 residues 418-444 as the minimal interaction domain and site-specific mutation of conserved acidic residues within this domain disrupted in vitro and in vivo binding. An IFNaR2 construct carrying these mutations was either (i) overexpressed in 293T cells or (ii) used to complement IFNaR2-deficient U5A cells. Unexpectedly, the activity of an IFNalpha dependent reporter gene was not reduced but, instead, was enhanced up to 2-fold. This suggests that this particular IFNaR2-Stat2 interaction is not required for IFNalpha signaling, but might act to negatively inhibit signaling. Finally, a doubly truncated recombinant fragment of Stat2, spanning residues 136-702, associated with IFNaR2 in vitro, indicating that the interaction with IFNaR2 is direct and occurs in a central region of Stat2 marked by a hydrophobic core. PMID- 11786547 TI - Kinetic dissection of alpha 1-antitrypsin inhibition mechanism. AB - Serpins (serine protease inhibitors) inhibit target proteases by forming a stable covalent complex in which the cleaved reactive site loop of the serpin is inserted into beta-sheet A of the serpin with concomitant translocation of the protease to the opposite of the initial binding site. Despite recent determination of the crystal structures of a Michaelis protease-serpin complex as well as a stable covalent complex, details on the kinetic mechanism remain unsolved mainly due to difficulties in measuring kinetic parameters of acylation, protease translocation, and deacylation steps. To address the problem, we applied a mathematical model developed on the basis of a suicide inhibition mechanism to the stopped-flow kinetics of fluorescence resonance energy transfer during complex formation between alpha(1)-antitrypsin, a prototype serpin, and proteases. Compared with the hydrolysis of a peptide substrate, acylation of the protease by alpha(1)-antitrypsin is facilitated, whereas deacylation of the acyl intermediate is strongly suppressed during the protease translocation. The results from nucleophile susceptibility of the acyl intermediate suggest strongly that the active site of the protease is already perturbed during translocation. PMID- 11786548 TI - Comparison of filamin A-induced cross-linking and Arp2/3 complex-mediated branching on the mechanics of actin filaments. AB - We compared the effects of human filamin A (FLNa) and the activated human Arp2/3 complex on mechanical properties of actin filaments. As little as 1 FLNa to 800 polymerizing actin monomers induces a sharp concentration-dependent increase in the apparent viscosity of 24 microm actin, a parameter classically defined as a gel point. The activated Arp2/3 complex, at concentrations up to 1:25 actins had no detectable actin gelation activity, even in the presence of phalloidin, to stabilize actin filaments against debranching. Increasing the activated Arp2/3 complex to actin ratio raises the FLNa concentration required to induce actin gelation, an effect ascribable to Arp2/3-mediated actin nucleation resulting in actin filament length diminution. Time lapse video microscopy of microparticles attached to actin filaments or photoactivation of fluorescence revealed actin filament immobilization by FLNa in contrast to diffusion of Arp2/3-branched actin filaments. The experimental results support theories predicting that polymer branching absent cross-linking does not lead to polymer gelation and are consistent with the observation that cells deficient in actin filament cross linking activity have unstable surfaces. They suggest complementary roles for actin branching and cross-linking in cellular actin mechanics in vivo. PMID- 11786549 TI - The oxidized lipid and lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid induces hypertrophy and fibronectin transcription in vascular smooth muscle cells via p38 MAPK and cAMP response element-binding protein activation. Mediation of angiotensin II effects. AB - Evidence suggests that the arachidonic acid metabolite of 12-lipoxygenase, 12(S) hydroxyeicosatetraenoic acid (12(S)-HETE), not only mediates the effects of angiotensin II (AngII), but also has direct effects on hypertrophy and matrix protein production in vascular smooth muscle cells (VSMCs). This study is aimed at identifying the signaling pathways involved in these events. Treatment of porcine VSMCs with 12(S)-HETE led to the activation of Ras and p38 MAPK. It also stimulated phosphorylation, DNA-binding activity, and transactivation of the transcription factor cAMP response element (CRE)-binding protein. In addition, 12(S)-HETE induced transcription from a fibronectin promoter containing multiple CREs. AngII also induced transactivation of CRE-binding protein and transcription from the fibronectin promoter. A specific p38 MAPK inhibitor (SB202190) as well as a dominant-negative Ras mutant (Ras-N17) blocked both 12(S)-HETE and AngII effects. In addition, inhibitors of lipoxygenase also blocked AngII effects. Both 12(S)-HETE and AngII increased cellular hypertrophy with similar potency, and this was significantly blocked by SB202190. Stable overexpression of murine leukocyte-type 12/15-lipoxygenase in VSMCs increased the levels of cell associated 12(S)-HETE as well as basal activity of both ERK and p38 MAPKs. Furthermore, these 12-lipoxygenase-overexpressing cells displayed significantly greater cellular hypertrophy relative to mock-transfected cells. These results show for the first time that oxidized lipids such as 12(S)-HETE can induce VSMC growth and matrix gene expression and mediate growth factor effects via activation of the Ras-MAPK pathway and key target transcription factors. PMID- 11786550 TI - Plasma membrane Ca2+ ATPase isoform 2b interacts preferentially with Na+/H+ exchanger regulatory factor 2 in apical plasma membranes. AB - Spatial and temporal regulation of Ca(2+) signaling require the assembly of multiprotein complexes linking molecules involved in Ca(2+) influx, sensing, buffering, and extrusion. Recent evidence indicates that plasma membrane Ca(2+) ATPases (PMCAs) participate in the control of local Ca(2+) fluxes, but the mechanism of multiprotein complex formation of specific PMCAs is poorly understood. Using the PMCA2b COOH-terminal tail as bait in a yeast two-hybrid screen, we identified the PSD-95, Dlg, ZO-1 (PDZ) domain-containing Na(+)/H(+) exchanger regulatory factor-2 (NHERF2) as an interacting partner. Protein pull down and coimmunoprecipitation experiments using recombinant PMCA2b and PMCA4b as well as NHERF1 and NHERF2 showed that the interaction of PMCA2b with NHERF2 was specific and selective. PMCA4b did not interact with either of the NHERFs, and PMCA2b selectively preferred NHERF2 over NHERF1. Green fluorescent protein-tagged PMCA2b was expressed at the apical membrane in Madin-Darby canine kidney epithelial cells, where it colocalized with apically targeted NHERF2. Our study identifies NHERF2 as the first specific PDZ partner for PMCA2b not shared with PMCA4b, and demonstrates that PMCA splice forms differing only minimally in their COOH-terminal residues interact with unique PDZ proteins. NHERFs have been implicated in the targeting, retention and regulation of membrane proteins including the beta(2)-adrenergic receptor, cystic fibrosis transmembrane conductance regulator, and Trp4 Ca(2+) channel, and NHERF2 is now shown to also interact with PMCA2b. This interaction may allow the functional assembly of PMCA2b in a multiprotein Ca(2+) signaling complex, facilitating integrated cross talk between local Ca(2+) influx and efflux. PMID- 11786551 TI - Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior. AB - In this study we have examined how unnatural sialic acids can alter polysialic acid expression and influence the adhesive properties of the neural cell adhesion molecule (NCAM). Unnatural sialic acids are generated by metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell-surface glycoconjugates. However, N-butanoylmannosamine and N-pentanoylmannosamine are effective inhibitors of polysialic acid (PSA) synthesis in stably transfected HeLa cells expressing NCAM and the polysialyltransferase STX. These cells were used as substrates to examine the effect of inhibiting PSA synthesis on the development of neurons derived from the chick dorsal root ganglion. N butanoylmannosamine blocked polysialylation of NCAM and significantly reduced neurite outgrowth comparable with enzymatic removal of PSA by endoneuraminidases. As a result, neurite outgrowth was similar to that observed for non polysialylated NCAM. In contrast, previous studies have shown that N-propanoyl sialic acid (SiaProp), generated from N-propanoylmannosamine, is readily accepted by polysialyltransferases and permits the extension of poly(SiaProp) on NCAM. Despite being immunologically distinct, poly(SiaProp) can promote neurite outgrowth similarly to natural polysialic acid. Thus, subtle structural differences in PSA resulting from the incorporation of SiaProp residues do not alter the antiadhesive properties of polysialylated NCAM. PMID- 11786552 TI - Amino acid residues in the P6-P'3 region of thrombin-activable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation. AB - Thrombin bound to thrombomodulin activates thrombin-activable fibrinolysis inhibitor (TAFI) and protein C much more efficiently than thrombin alone. Although thrombomodulin has been proposed to alter the thrombin active site, the recently determined structure of the thrombin-thrombomodulin complex does not support this proposal. In this study, the contribution of amino acids near the activation site of TAFI toward thrombomodulin dependence was determined, utilizing four variants of TAFI with specific substitutions in the P6-P'3 region surrounding the Arg-92 cleavage site. Two point mutants had either the Ser-90 or Asp-87 of TAFI replaced with Ala, a third mutant had the thrombin activation site of the fibrinogen Bbeta-chain substituted into positions 91-95 of TAFI, and a fourth mutant had the thrombin activation site of protein C substituted into positions 90-95 of TAFI. Each of these mutants was expressed, purified, and characterized with respect to activation kinetics and functional properties of the enzyme. Even though fibrinogen is poorly cleaved by thrombin-thrombomodulin, the fibrinogen activation site does not significantly alter the thrombomodulin dependence of TAFI activation. The TAFI variant with the protein C activation sequence is only slowly activated by thrombin-thrombomodulin, and not at all by free thrombin. Mutating Asp-87 to Ala increases the catalytic efficiency of activation 3-fold both in the presence and absence of thrombomodulin, whereas mutating Ser-90 to Ala effects only minor kinetic differences compared with wild type TAFI. The thermal stabilities and antifibrinolytic properties of the enzymes were not substantially altered by any of the mutations that allowed for efficient activation of the enzyme. We conclude that residues in the P6-P'3 region of TAFI do not determine the thrombomodulin dependence of activation, which lends support to the argument that the role of thrombomodulin is to optimally orient thrombin and its substrate, rather than to allosterically alter the specificity of the thrombin active site. PMID- 11786553 TI - The anti-trp RNA-binding attenuation protein (Anti-TRAP), AT, recognizes the tryptophan-activated RNA binding domain of the TRAP regulatory protein. AB - In Bacillus subtilis, the trp RNA-binding attenuation protein (TRAP) regulates expression of genes involved in tryptophan metabolism in response to the accumulation of l-tryptophan. Tryptophan-activated TRAP negatively regulates expression by binding to specific mRNA sequences and either promoting transcription termination or blocking translation initiation. Conversely, the accumulation of uncharged tRNA(Trp) induces synthesis of an anti-TRAP protein (AT), which forms a complex with TRAP and inhibits its activity. In this report, we investigate the structural features of TRAP required for AT recognition. A collection of TRAP mutant proteins was examined that were known to be partially or completely defective in tryptophan binding and/or RNA binding. Analyses of AT interactions with these proteins were performed using in vitro transcription termination assays and cross-linking experiments. We observed that TRAP mutant proteins that had lost the ability to bind RNA were no longer recognized by AT. Our findings suggest that AT acts by competing with messenger RNA for the RNA binding domain of TRAP. B. subtilis AT was also shown to interact with TRAP proteins from Bacillus halodurans and Bacillus stearothermophilus, implying that the structural elements required for AT recognition are conserved in the TRAP proteins of these species. Analyses of AT interaction with B. stearothermophilus TRAP at 60 degrees C demonstrated that AT is active at this elevated temperature. PMID- 11786554 TI - A new substrate specificity for acyl transferase domains of the ascomycin polyketide synthase in Streptomyces hygroscopicus. AB - Ascomycin (FK520) is a structurally complex macrolide with immunosuppressant activity produced by Streptomyces hygroscopicus. The biosynthetic origin of C12 C15 and the two methoxy groups at C13 and C15 has been unclear. It was previously shown that acetate is not incorporated into C12-C15 of the macrolactone ring. Here, the acyl transferase (AT) of domain 8 in the ascomycin polyketide synthase was replaced with heterologous ATs by double homologous recombination. When AT8 was replaced with methylmalonyl-CoA-specific AT domains, the strains produced 13 methyl-13-desmethoxyascomycin, whereas when AT8 was replaced with a malonyl specific domain, the strains produced 13-desmethoxyascomycin. These data show that ascomycin AT8 does not use malonyl- or methylmalonyl-CoA as a substrate in its native context. Therefore, AT8 must be specific for a substrate bearing oxygen on the alpha carbon. Feeding experiments showed that [(13)C]glycerol is incorporated into C12-C15 of ascomycin, indicating that both modules 7 and 8 of the polyketide synthase use an extender unit that can be derived from glycerol. When AT6 of the 6-deoxyerythronolide B synthase gene was replaced with ascomycin AT8 and the engineered gene was expressed in Streptomyces lividans, the strain produced 6-deoxyerythronolide B and 2-demethyl-6-deoxyerythronolide B. Therefore, although neither malonyl-CoA nor methylmalonyl-CoA is a substrate for ascomycin AT8 in its native context, both are substrates in the foreign context of the 6 deoxyerythronolide B synthase. Thus, we have demonstrated a new specificity for an AT domain in the ascomycin polyketide synthase and present evidence that specificity can be affected by context. PMID- 11786555 TI - Regulation of enhanced vacuolar H+-ATPase expression in macrophages. AB - The proton-translocating vacuolar ATPase (V-ATPase) acidifies the endocytic network of eukaryotic cells. Although all eukaryotic cell types require low to moderate levels of V-ATPase, some proton-secreting cells express amplified levels for use in specialized membrane domains. To characterize genetic elements required for this heightened expression, we studied transcription and stability of mRNA encoding the V-ATPase c subunit in a low expressing fibroblast cell line (NIH 3T3) and a high expressing macrophage cell line (RAW 264.7). Isolation of the promoter and mapping of the transcriptional start site indicated that the c subunit promoter is TATA-less and initiates transcription at a single site. Promoter activity was regulated through the same transcription factor binding sites in both cell types, which showed no discernible difference in rates of c subunit transcription. In contrast, c subunit transcripts showed markedly greater stability in RAW cells than in 3T3 cells, as did other constitutively expressed V ATPase subunit transcripts. Only the B and 'a' subunits, which are expressed in multiple isoforms, were not regulated solely by mRNA stability. These results suggest that overall expression levels of the V-ATPase are set primarily by regulation of mRNA stability and that transcriptional mechanisms determine subunit composition in varying cell types. PMID- 11786556 TI - PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B. AB - The PYRIN domain is a recently identified protein-protein interaction domain that is found at the N terminus of several proteins thought to function in apoptotic and inflammatory signaling pathways. We report here that PYPAF1 (PYRIN-containing Apaf1-like protein 1) is a novel PYRIN-containing signaling protein that belongs to the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signaling proteins. The expression of PYPAF1 is highly restricted to immune cells, and its gene maps to chromosome 1q44, a locus that is associated with the rare inflammatory diseases Muckle-Wells syndrome and familial cold urticaria. To identify downstream signaling partners of PYPAF1, we performed a mammalian two hybrid screen and identified ASC as a PYRIN-containing protein that interacts selectively with the PYRIN domain of PYPAF1. When expressed in cells, ASC recruits PYPAF1 to distinct cytoplasmic loci and induces the activation of NF kappaB. Furthermore, coexpression of PYPAF1 with ASC results in a potent synergistic activation of NF-kappaB. These findings suggest that PYPAF1 and ASC function as upstream activators of NF-kappaB signaling. PMID- 11786557 TI - Twists and turns of the cation-dependent mannose 6-phosphate receptor. Ligand bound versus ligand-free receptor. AB - Mannose 6-phosphate receptors (MPRs) participate in the biogenesis of lysosomes in higher eukaryotes by transporting soluble acid hydrolases from the trans-Golgi network to late endosomal compartments. The receptors release their ligands into the acidic environment of the late endosome and then return to the trans-Golgi network to repeat the process. However, the mechanism that facilitates ligand binding and dissociation upon changes in pH is not known. We report the crystal structure of the extracytoplasmic domain of the homodimeric cation-dependent MPR in a ligand-free form at pH 6.5. A comparison of the ligand-bound and ligand-free structures reveals a significant change in quaternary structure as well as a reorganization of the binding pocket, with the most prominent change being the relocation of a loop (residues Glu(134)-Cys(141)). The movements involved in the bound-to-free transition of the cation-dependent MPR are reminiscent of those of the oxy-to-deoxy hemoglobin transition. These results allow us to propose a mechanism by which the receptor regulates its ligand binding upon changes in pH; the pK(a) of Glu(133) appears to be responsible for ligand release in the acidic environment of the late endosomal compartment, and the pK(a) values of the sugar phosphate and His(105) are accountable for its inability to bind ligand at the cell surface where the pH is about 7.4. PMID- 11786559 TI - Receptor-dependent metabolism of platelet-activating factor in murine macrophages. AB - Degradation of platelet-activating factor (PAF) was examined by incubating PAF with macrophages from PAF receptor-deficient mice. The degradation rate was halved as compared with wild-type mice. The reduction of the rate was comparable with the presence of a PAF antagonist WEB 2086 in wild-type cells. PAF was internalized rapidly (t(12) approximately 1 min) into wild-type macrophages. The PAF internalization was inhibited by the treatment of 0.45 m sucrose but was not affected by phorbol 12-myristate 13-acetate, suggesting that PAF internalizes into macrophages with its receptor in a clathrin-dependent manner. Internalized PAF was degraded into lyso-PAF with a half-life of 20 min. Treatment of concanavalin A inhibited the conversion of PAF into lyso-PAF, suggesting that uptake of PAF enhances PAF degradation. Lyso-PAF was subsequently metabolized into 1-alkyl-2-acyl-phosphatidylcholine. In addition, release of PAF acetylhydrolase from macrophages was enhanced when wild-type macrophages were stimulated with PAF but not from macrophages of PAF receptor-deficient mice. Thus, the PAF stimulation of macrophages leads to its degradation through both intracellular and extracellular mechanisms. PMID- 11786558 TI - Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes. AB - Although oxidative stress causes activation of c-Jun N-terminal kinase (JNK) and apoptosis in many cell types, how the JNK pathway is connected to the apoptosis pathway is unclear. The molecular mechanism of JNK-mediated apoptosis was investigated in adult rat cardiac myocytes in culture as a model system that is sensitive to oxidative stress. Oxidative stress caused JNK activation, cytochrome c release, and apoptosis without new protein synthesis. Oxidative stress-induced apoptosis was abrogated by dominant negative stress-activated protein kinase/extracellular signal-regulated kinase kinase-1 (SEK1)-mediated inhibition of the JNK pathway, whereas activation of the JNK pathway by constitutively active SEK1 was sufficient to cause apoptosis. Inhibition of caspase-9, an apical caspase in the mitochondrial apoptosis pathway, suppressed oxidative stress induced apoptosis, whereas inhibition of caspase-8 had no effect, indicating that both the JNK pathway and the mitochondrial apoptosis machinery are central to oxidative stress-induced apoptosis. Both JNK and SEK1 localized on mitochondria where JNK was activated by oxidative stress. Furthermore, active JNK caused the release of apoptogenic factors such as cytochrome c from isolated mitochondria in a cell-free assay. These findings indicate that the JNK pathway is a direct activator of mitochondrial death machinery without other cellular components and provide a molecular linkage from oxidative stress to the mitochondrial apoptosis machinery. PMID- 11786560 TI - Searching for a standard. PMID- 11786561 TI - Adenosine triphosphate: does it help cancer patients "get bigger and stronger"? PMID- 11786562 TI - Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer. AB - PURPOSE: The purpose of this study was to test interferon alfa (IFNalpha), 13-cis retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin. PATIENTS AND METHODS: Patients with advanced skin SCC received IFNalpha (5 x 10(6) IU/m(2), subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m(2), intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1 m7 and SRB12-p9). RESULTS: Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines. CONCLUSION: The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFNalpha, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non-cross-resistant biologic effects in vitro, which may account for the combination's clinical activity. PMID- 11786563 TI - Beneficial effects of adenosine triphosphate on nutritional status in advanced lung cancer patients: a randomized clinical trial. AB - PURPOSE: In a randomized clinical trial in patients with advanced non-small-cell lung cancer (NSCLC), infusion with adenosine 5'-triphosphate (ATP) inhibited loss of body weight and quality of life. In the present article, the effects of ATP on body composition, energy intake, and energy expenditure as secondary outcome measures in the same patients are reported. PATIENTS AND METHODS: Patients with NSCLC, stage IIIB or IV, were randomized to receive either 10 intravenous, 30 hour ATP infusions every 2 to 4 weeks or no ATP. Fat mass (FM), fat-free mass (FFM), and arm muscle area were assessed at 4-week intervals for 28 weeks. Food intake, body cell mass (BCM), and resting energy expenditure (REE) were assessed at 8-week intervals for 16 weeks. Between-group differences were tested for statistical significance by repeated-measures analysis of covariance. RESULTS: Fifty-eight patients were randomized (28 ATP, 30 control). No change in body composition over the 28-week follow-up period was found in the ATP group, whereas, per 4 weeks, the control group lost 0.6 kg of FM (P =.004), 0.5 kg of FFM (P =.02), 1.8% of arm muscle area (P =.02), and 0.6% of BCM/kg body weight (P =.054) and decreased 568 KJ/d in energy intake (P =.0001). Appetite also remained stable in the ATP group but decreased significantly in the control group (P =.0004). No significant differences in REE between the ATP and control groups were observed. CONCLUSION: The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues. These effects are partly ascribed to maintenance of energy intake. PMID- 11786564 TI - Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. AB - PURPOSE: Variable uptake of the glucose analog (18)fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. PATIENTS AND METHODS: Preoperative (18)FDG-PET scans were performed in 55 patients. (18)FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1alpha); vascular endothelial growth factor (VEGF(165)); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. RESULTS: There were positive correlations between (18)FDG uptake and Glut-1 expression (P <.001), MAI (P =.001), amount of necrosis (P =.010), number of tumor cells/volume (P =.009), expression of HK I (P =.019), number of lymphocytes (P =.032), and microvessel density (r =.373; P =.005). HIF-1alpha, VEGF(165), HK II, HK III, and macrophages showed no univariate correlation with (18)FDG. In logistic regression, however, HIF-1alpha and HK II added value to MAI and Glut-1. CONCLUSION: (18)FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of (18)FDG into the cell, HK for entering (18)FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1alpha for upregulating Glut-1. Together, these features explain why breast cancers vary in (18)FDG uptake and elucidate the low uptake in lobular breast cancer. PMID- 11786565 TI - Value of positron emission tomography with [F-18]fluorodeoxyglucose in patients with colorectal liver metastases: a prospective study. AB - PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease. PMID- 11786566 TI - Clinical value of iodine-123-alpha-methyl-L-tyrosine single-photon emission tomography in the differential diagnosis of recurrent brain tumor in patients pretreated for glioma at follow-up. AB - PURPOSE: To assess the clinical potential of iodine-123-alpha-methyl-L-tyrosine (IMT) and single-photon emission tomography (SPET) in the differential diagnosis of recurrences in patients pretreated for gliomas at follow-up. PATIENTS AND METHODS: Seventy-eight patients were examined after primary therapy over 36 months. Histopathologic diagnoses of all patients was known at first treatment; magnetic resonance and/or computed tomography examination was performed in addition to IMT-SPET. Cerebral SPET images were acquired 20 minutes after intravenous application of 190 +/- 10 MBq of IMT. SPET images were classified as positive or negative for recurrent tumor visually and by calculating the ratios between tracer accumulation in the lesion and the unaffected contralateral regions of reference using region of interest. Final diagnoses were based on prospective clinicopathologic findings obtained independently of IMT-SPET. RESULTS: IMT-SPET detected all high-grade recurrent gliomas (grade 4; sensitivity, 100%). A difference could be demonstrated in grade 2 and 3 recurrences (sensitivity, 84% and 92%, respectively). Moreover, benign posttherapeutic lesions (postoperative scars, radiation necrosis) were correctly diagnosed as negative for tumor recurrence. In general, IMT uptake in grade 2 (1.45 +/- 0.24) was significantly lower than that in grades 3 (1.70 +/- 0.41) and 4 (1.88 +/- 0.32). However, it was difficult to evaluate tumor grade only from the IMT accumulation in individual cases. CONCLUSION: IMT-SPET seems highly useful for detecting and delineating recurrent gliomas and differentiating between benign posttherapeutic lesions and malignant tumor tissue. It may be a valuable clinical tool to diagnose recurrences in patients pretreated for gliomas at follow-up. However, it showed limitations in determining histologic tumor grade. PMID- 11786567 TI - Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. AB - PURPOSE: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs. PATIENTS AND METHODS: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided. RESULTS: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1 year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. CONCLUSION: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem. PMID- 11786568 TI - Accuracy of recorded tumor, node, and metastasis stage in a comprehensive cancer center. AB - PURPOSE: The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program. PATIENTS AND METHODS: All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed. RESULTS: A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned. CONCLUSION: This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs. PMID- 11786569 TI - Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. AB - PURPOSE: Temozolomide is a novel oral alkylating agent that is effective against melanoma. Moreover, temozolomide readily crosses the blood-brain barrier and may consequently be effective in patients with brain metastases. This phase II study was performed to assess the efficacy and safety of the combination regimen of temozolomide and docetaxel in patients with advanced metastatic melanoma. PATIENTS AND METHODS: Sixty-five patients with metastatic melanoma were enrolled. Treatment consisted of intravenous docetaxel (80 mg/m(2)) on day 1 and oral temozolomide (150 mg/m(2)) on days 1 to 5, every 4 weeks, for a maximum of six cycles. RESULTS: Sixty-two patients were eligible for the efficacy and safety analysis. Seventeen patients (27%) achieved an objective response, including five complete (8%) and 12 partial responses (19%). Median response duration was 9.5 months. Among responders, median time to progression (TTP) was 11.2 months and median overall survival (OS) was 16 months. For all treated patients, the median TTP was 4 months and median OS was 11 months. Three (38%) of eight patients who presented with brain metastases had a partial response for 5, 6, and 12 months. Of 52 patients who did not have brain involvement at presentation, only four (8%) developed brain metastases at a median follow-up of 14 months. Myelosuppression was the primary toxicity. CONCLUSION: The combination of temozolomide and docetaxel was effective and well tolerated as first-line treatment for patients with advanced metastatic melanoma and demonstrated encouraging antitumor activity against brain metastases. PMID- 11786570 TI - Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. AB - PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. PATIENTS AND METHODS: Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% +/- 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% +/- 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% +/- 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi's syndrome was observed in five patients. CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity. PMID- 11786571 TI - Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group. AB - PURPOSE: We report the first large prospective study of children with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) treated in a uniform fashion on Children's Cancer Group protocol 2891. PATIENTS AND METHODS: Ninety children with JMML, various forms of MDS, or acute myeloid leukemia (AML) with antecedent MDS were treated with a five-drug induction regimen (standard or intensive timing). Patients achieving remission were allocated to allogeneic bone marrow transplantation (BMT) if a matched family donor was available. All other patients were randomized between autologous BMT and aggressive nonmyeloablative chemotherapy. Results were compared with patients with de novo AML. RESULTS: Patients with JMML and refractory anemia (RA) or RA excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58% and 48%, respectively. Remission rates for patients with RAEB in transformation (RAEB-T) (69%) or antecedent MDS (81%) were similar to de novo AML (77%). Actuarial survival rates at 6 years were as follows: JMML, 31% +/- 26%; RA and RAEB, 29% +/- 16%; RAEB-T, 30% +/- 18%; antecedent MDS, 50% +/- 25%; and de novo AML, 45% +/- 3%. For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy. The presence of monosomy 7 had no additional adverse effect on MDS and JMML. CONCLUSION: Childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes. Children with a history of MDS who present with AML do well with AML-type therapy. Patients with RA or RAEB respond poorly to AML induction therapy. The optimum treatment for JMML remains unknown. PMID- 11786572 TI - Granulocyte colony-stimulating factor in induction treatment of children with non Hodgkin's lymphoma: a randomized study of the French Society of Pediatric Oncology. AB - PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF; lenograstim) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients were randomized to receive (G-CSF+) or not receive (G-CSF-) prophylactic G-CSF, 5 microg/kg/d, from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours, after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2), vincristine 2 mg/m(2), prednisone 60 mg/m(2)/d x 5, doxorubicin 60 mg/m(2), high-dose methotrexate 3 or 8 g/m(2), and intrathecal injections (COPAD[M]) on protocols LMB89, LMT89, and HM91 of the French Society of Pediatric Oncology. RESULTS: One hundred forty-eight patients were assessable, 75 G-CSF+ and 73 G-CSF-. Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients (P = 10(-4)), incidence of febrile neutropenia (89% v. 93% in the first course, 88% v. 88% in the second course), durations of hospitalization and antimicrobial therapy, percentages of infections, mucositis, and transfusions were not significantly different. Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher (84% v 68% after the first and 57% v. 38% after the second course; P <.05), the median delay between the two courses was only 1 day less in G-CSF+ patients (median delay after first COPAD(M), 19 v. 20 days, P =.01; after second, 21 v. 22 days, P = not significant). Remission and survival rates were similar in both arms. CONCLUSION: This study demonstrates that G-CSF did not decrease treatment-related morbidity, nor increase the dose-intensity in children undergoing COPAD(M) induction chemotherapy for NHL. PMID- 11786573 TI - Paratesticular rhabdomyosarcoma: report from the Italian and German Cooperative Group. AB - PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years. PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients. RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor. CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent-free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse. PMID- 11786574 TI - Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias. AB - PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies. PMID- 11786575 TI - Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. AB - PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis. PMID- 11786576 TI - Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial. AB - PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory. PMID- 11786578 TI - Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. AB - PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P <.04), particularly in the domains of verbal memory (P <.01) and psychomotor functioning (P <.03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P <.01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P <.02). CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy. PMID- 11786577 TI - Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. AB - PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results. PMID- 11786579 TI - Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. AB - PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano's index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two fold higher probability of having an elevated Satariano's index than independent patients. A strong association emerged between PS and CGA, with a nearly five fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients. PMID- 11786580 TI - When the treatment goal is not cure: are cancer patients equipped to make informed decisions? AB - PURPOSE: Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions. PATIENTS AND METHODS: One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes. RESULTS: Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P =.0005), which persisted over a 2-week time span. CONCLUSION: Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment. PMID- 11786581 TI - Impact of BRCA1/BRCA2 mutation testing on psychologic distress in a clinic-based sample. AB - PURPOSE: Despite the increasingly widespread availability of BRCA1 and BRCA2 genetic testing, little is known about the psychologic impact of such testing in the clinical setting. The objective of this study was to examine the long-term psychologic impact of receiving BRCA1/2 test results within a clinic-based testing program. PATIENTS AND METHODS: The participants were 279 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. At baseline (before genetic testing) and at 6 months after the disclosure of mutation status, we measured perceived risk for breast and ovarian cancer, cancer-specific distress, and general distress. We examined the impact of the test result on each of these outcomes at the 6-month follow-up. Analyses were conducted separately for probands and their relatives who were unaffected with cancer. RESULTS: We found no effect of test result among affected probands. Among unaffected relatives, we found that participants who received definitive negative test results exhibited significant reductions in perceived risk and distress compared with participants who received positive test results. Importantly, relatives who received positive test results did not exhibit increased distress or perceived risk. CONCLUSION: These results suggest that clinic-based BRCA1/2 testing can lead to psychologic benefits for individuals who receive negative test results. At 6 months after disclosure, those who receive positive or uninformative test results do not exhibit increased psychologic distress or perceived risk. PMID- 11786582 TI - Extraosseous osteosarcoma: response to treatment and long-term outcome. AB - PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy. PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome. RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m(2); median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence-free, distant recurrence-free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively. CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low. PMID- 11786583 TI - Identification and referral of families at high risk for cancer susceptibility. AB - PURPOSE: Obtainment of family history and accurate assessment is essential for the identification of families at risk for hereditary cancer. Our study compared the extent to which the family cancer history in the physician medical record reflected that entered by patients directly into a touch-screen family history computer program. PATIENTS AND METHODS: The study cohort consisted of 362 patients seen at a comprehensive cancer center ambulatory clinic over a 1-year period who voluntarily used the computer program and were a mixture of new and return patients. The computer entry was assessed by genetics staff and then compared with the medical record for corroboration of family history information and appropriate physician risk assessment. RESULTS: Family history information from the medical record was available for comparison to the computer entry in 69%. It was most often completed on new patients only and not routinely updated. Of the 362 computer entries, 101 were assigned to a high-risk category. Evidence in the records confirmed 69 high-risk individuals. Documentation of physician risk assessment (ie, notation of significant family cancer history or hereditary risk) was found in only 14 of the high-risk charts. Only seven high-risk individuals (6.9%) had evidence of referral for genetic consultation. CONCLUSION: This study demonstrates the need to collect family history information on all new and established patients in order to perform adequate cancer risk assessment. The lack of identification of patients at highest risk seems to be directly correlated with insufficient data collection, risk assessment, and documentation by medical staff. PMID- 11786584 TI - 13-cis retinoic acid and complete androgen blockade in advanced hormone-naive prostate cancer patients: report of a phase II randomized study. AB - PURPOSE: 13 cis Retinoic acid (isotretinoin) is a retinoid with preclinical evidence of anti-prostate cancer activity. This phase II, cross-over, randomized study of advanced, predominantly androgen-dependent prostate cancer patients was designed to assess primarily the effect on prostate-specific antigen (PSA) decline and toxicity of adding isotretinoin to hormonal therapy and, secondarily, the potential antitumor activity of the combination. PATIENTS AND METHODS: Thirty seven D0 to D2 patients were randomized soon after initiating luteinizing hormone releasing hormone agonist with antiandrogen treatment to add (arm 1) or not (arm 2) isotretinoin from weeks 1 to 12. After cross-over on week 13, patients in arm 1 discontinued while patients in arm 2 added isotretinoin from weeks 14 to 25. Observation on hormonal therapy alone continued until week 49. RESULTS: Baseline and randomization median PSA for 30 assessable patients were, respectively, 34 and 18.2 ng/mL for arm 1 and 31 and 13.4 ng/mL for arm 2. Median PSA at week 13 was 0.5 ng/mL (range, < 0.05 to 136 ng/mL) for arm 1 and 0.7 ng/mL (range, < 0.05 to 4.4 ng/mL) for arm 2; at week 25, 0.1 ng/mL (range, < 0.05 to 121 ng/mL) and 0.4 ng/mL (range, < 0.05 to 3.1 ng/mL), respectively. At week 49, arm 1 had median PSA of 0.1 ng/mL (range, < 0.05 to 345 ng/mL) and arm 2, 0.3 ng/mL (range, < 0.05 to 8.8 ng/mL); seven of 15 and three of 15 patients, respectively, had undetectable PSA levels (P =.12). Frequent isotretinoin-related toxicity included grade 1 cheilitis (76%), skin dryness (43%), and elevated triglycerides (50%). CONCLUSION: Isotretinoin does not impair PSA decline or add significant toxicity to hormonal therapy. An adequately powered, randomized study would be required to determine whether the combination is superior to standard hormonal treatment. PMID- 11786585 TI - Factors affecting workload of cancer clinical trials: results of a multicenter study of the National Cancer Institute of Canada Clinical Trials Group. AB - PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials' task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use. PMID- 11786586 TI - Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. AB - PURPOSE: Health-related quality-of-life (HRQOL) concerns are pivotal in choosing prostate cancer therapy. However, concurrent HRQOL comparison between brachytherapy, external radiation, radical prostatectomy, and controls is hitherto lacking. HRQOL effects of hormonal adjuvants and of cancer control after therapy also lack prior characterization. PATIENTS AND METHODS: A cross-sectional survey was administered to patients who underwent brachytherapy, external-beam radiation, or radical prostatectomy during 4 years at an academic medical center and to age-matched controls. HRQOL among controls was compared with therapy groups. Comparison between therapy groups was performed using regression models to control covariates. HRQOL effects of cancer progression were evaluated. RESULTS: One thousand fourteen subjects participated. Compared with controls, each therapy group reported bothersome sexual dysfunction; radical prostatectomy was associated with adverse urinary HRQOL; external-beam radiation was associated with adverse bowel HRQOL; and brachytherapy was associated with adverse urinary, bowel, and sexual HRQOL (P < or =.0002 for each). Hormonal adjuvant symptoms were associated with significant impairment (P <.002). More than 1 year after therapy, several HRQOL outcomes were less favorable among subjects after brachytherapy than after external radiation or radical prostatectomy. Progression-free subjects reported better sexual and hormonal HRQOL than subjects with increasing prostate specific antigen (P <.0001). CONCLUSION: Long-term HRQOL after prostate brachytherapy showed no benefit relative to radical prostatectomy or external beam radiation and may be less favorable in some domains. Hormonal adjuvants can be associated with significant impairment. Progression-free survival is associated with HRQOL benefits. These findings facilitate patient counseling regarding HRQOL expectations and highlight the need for prospective studies sensitive to urinary irritative and hormonal concerns in addition to incontinence, sexual, and bowel HRQOL domains. PMID- 11786587 TI - Dronabinol versus megestrol acetate versus combination therapy for cancer associated anorexia: a North Central Cancer Treatment Group study. AB - PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit. PMID- 11786588 TI - Comparative pharmacokinetics of unbound paclitaxel during 1- and 3-hour infusions. AB - PURPOSE: The paclitaxel vehicle Cremophor EL (CrEL) profoundly influences the cellular distribution of paclitaxel in human blood in vitro by a concentration dependent decrease of the unbound drug fraction. Because CrEL clearance increases by extending the infusion duration from 3 to 24 hours, we hypothesized that exposure to unbound paclitaxel might also be schedule-dependent. PATIENTS AND METHODS: CrEL and unbound paclitaxel pharmacokinetics were prospectively analyzed in 29 patients with advanced solid tumors treated with paclitaxel 100 mg/m(2) given as a 1-hour (n = 15) or 3-hour (n = 14) intravenous infusion. RESULTS: The systemic exposure (area under the curve [AUC]) to CrEL was significantly higher with the 1-hour as compared with the 3-hour schedule (80.2 +/- 24.2 v. 48.5 +/- 24.1 microL x h/mL; P =.002). In contrast, the AUC of unbound paclitaxel was substantially reduced after the 1-hour infusion (0.50 +/- 0.10 v. 0.62 +/- 0.12 micromol/L x h; P =.009). Similarly, clearance and volume of distribution were significantly dependent on infusion duration (P <.005). A trend was observed toward more severe hematologic toxicity with the 3-hour schedule (P =.053), consistent with increased exposure to unbound drug. CONCLUSION: Overall, these findings explain, at least in part, previous observations that short-infusion schedules of paclitaxel lack significant myelotoxicity, whereas potentially CrEL related side effects, including peripheral neuropathy, are augmented. PMID- 11786589 TI - Dose-escalating study of capecitabine plus gemcitabine combination therapy in patients with advanced cancer. AB - PURPOSE: The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination. PATIENTS AND METHODS: Eligible patients had advanced solid tumors that had failed to respond to standard therapy or for which no standard therapy was available, measurable or assessable disease, Karnofsky performance status > or = 70%, and acceptable organ function. Capecitabine was administered twice daily by mouth each day for 21 consecutive days followed by a 1-week break. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break. RESULTS: Forty patients were enrolled onto the study, and 33 are fully assessable for toxicity. The most common toxicities during the first cycle of chemotherapy were neutropenia and mucositis. Only one patient treated at gemcitabine and capecitabine doses of 800 and 2000 mg/m(2), respectively, met protocol-specified DLT criteria; however, at these doses 65% of successive cycles required dose reduction or delay for toxicity. No episodes of DLT were observed at gemcitabine and capecitabine doses of 1,000 and 1,660 mg/m(2), respectively, and 70% of cycles of therapy were delivered without dose reduction or delay. Therefore, these doses are recommended for further study. Tumor responses were observed in patients with metastatic colorectal and pancreatic cancer. CONCLUSION: Gemcitabine and capecitabine can be combined with acceptable toxicity at nearly full doses. Antitumor activity of the combination merits further investigation in phase II studies. PMID- 11786590 TI - Merkel cell carcinoma. PMID- 11786591 TI - Intravenous immunoglobulin for hemophagocytic lymphohistiocytosis? PMID- 11786592 TI - Multinomial phase II trial designs. PMID- 11786593 TI - Management of anemia in patients receiving chemotherapy. PMID- 11786594 TI - Chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell transplantation: a little methotrexate goes a long way. PMID- 11786595 TI - Resistin gene expression in human adipocytes is not related to insulin resistance. AB - OBJECTIVES: Obesity is an important risk factor for the development of insulin resistance and type 2 diabetes. Recently, a newly described circulating hormone resistin, which is expressed primarily in adipocytes, has been shown to antagonize insulin action in mice. Resistin, therefore, has been suggested to play a role in the pathogenesis of insulin resistance. RESEARCH METHODS AND PROCEDURES: We studied the expression of the resistin gene in primary cultured human adipocytes and preadipocytes. We also examined resistin gene expression in subcutaneous abdominal adipocytes in women (n = 24) over a wide range of body weight and insulin sensitivity. RESULTS: Whereas resistin gene expression was barely detectable in mature adipocytes, it was highly expressed in preadipocytes. Adipogenic differentiation of preadipocytes was associated with a time-dependent down-regulation of resistin gene expression. There was no relationship between body weight, insulin sensitivity, or other metabolic parameters and adipocyte resistin gene expression in the clinical study. DISCUSSION: Together these findings do not support an important role of adipose-tissue resistin gene expression in human insulin resistance. PMID- 11786596 TI - Plasma leptin response to an epinephrine infusion in lean and obese women. AB - OBJECTIVE: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. RESEARCH METHODS AND PROCEDURES: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 microg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index +/- SD: 22.6 +/- 1.1 kg/m(2)) and 15 obese (30.0 +/- 1.3 kg/m(2)) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (-15 and 0 minutes) and at every 30 minutes over the 90-minute period. RESULTS: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = -0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from -12 to -570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = -0.14, p = 0.55). DISCUSSION: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals. PMID- 11786597 TI - Leptin's sexual dimorphism results from genotype by sex interactions mediated by testosterone. AB - OBJECTIVE: Recent studies have reported the existence of marked sexual dimorphism in serum leptin levels in humans, with women having approximately three times the levels of men. As we have shown for other measures of adiposity, such sexual dimorphism can arise from a special case of genotype by environment interaction, that of genotype by sex interaction. RESEARCH METHODS AND PROCEDURES: Using maximum likelihood-based variance decomposition techniques, we examined the genetic and environmental architecture of sexual dimorphism in serum leptin levels in 1147 Mexican Americans from the San Antonio Family Heart Study. RESULTS: Both the genetic and environmental variances for this trait differed significantly between the sexes (p < 0.001 and p < 0.01, respectively), with women displaying larger values for both components. We found significant evidence that different genes influence variation in serum leptin levels between the two sexes (p = 0.05). Furthermore, this pattern of sexual dimorphism in serum leptin levels persisted even after accounting for the effects of either the percentage of body fat or total body fat. However, this pattern of sexual dimorphism was eliminated after accounting for the effects of testosterone. DISCUSSION: These findings suggest that the sexual dimorphism seen in leptin levels is not simply explained as differences in total adiposity between the sexes. We conclude that the genes, which influence variation in serum leptin levels, are differentially expressed depending on sex, and that the sexes also show differences in response of the expression of this obesity-related trait to unmeasured residual effects. PMID- 11786598 TI - Behavioral weight control for overweight adolescents initiated in primary care. AB - OBJECTIVE: This study evaluates the post-treatment and short-term follow-up efficacy of, as well as participant satisfaction for, a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact. RESEARCH METHODS AND PROCEDURES: 44 overweight adolescents were randomly assigned to either a multiple component behavioral weight control intervention (Healthy Habits [HH]; n = 23) or a single session of physician weight counseling (typical care [TC]; n = 21). Weight, height, dietary intake, physical activity, sedentary behavior, and problematic weight-related and eating behaviors and beliefs were assessed before treatment, after the 4-month treatment, and at 3-month follow-up. Participant satisfaction and behavioral skills use were measured. RESULTS: HH adolescents evidenced better change in body mass index z scores to post-treatment than TC adolescents. Body mass index z scores changed similarly in the conditions from post-treatment through follow-up. Behavioral skills use was higher among HH than TC adolescents, and higher behavioral skills use was related to better weight outcome. Energy intake, percentage of calories from fat, physical activity, sedentary behavior, and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition. The behavioral intervention evidenced good feasibility and participant satisfaction. DISCUSSION: A telephone- and mail-based behavioral intervention initiated in primary care resulted in better weight control efficacy relative to care typically provided to overweight adolescents. Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth. PMID- 11786599 TI - Body image partially mediates the relationship between obesity and psychological distress. AB - OBJECTIVE: Body image is considered as a potential mediator of the relationship between obesity and psychological distress. RESEARCH METHODS AND PROCEDURES: One hundred ten men and women in a residential weight control facility completed the Multidimensional Body Self-Relations Questionnaire, the Beck Depression Inventory, the Rosenberg Self-Esteem Scale, and the Binge Eating Scale. RESULTS: For both men and women, body-image satisfaction partially mediated the relationship between degree of overweight and depression/self-esteem. DISCUSSION: Sociodemographic factors that may influence the relationships among weight, body image, and depression/self-esteem are discussed. PMID- 11786600 TI - Dietary patterns and their associations with obesity in the Brazilian city of Rio de Janeiro. AB - OBJECTIVE: To evaluate the dietary patterns of adults living in the city of Rio de Janeiro, Brazil and their associations with body mass index (BMI). RESEARCH METHODS AND PROCEDURES: A survey was conducted in 1996 in a probabilistic sample of 2040 households. Weight and height were measured and food intake was based on an 80-item semi-quantitative food frequency questionnaire. Dietary patterns were identified through factor analysis. RESULTS: More than one-third of the adult population (20 to 60 years old) was overweight (BMI = 25 to 29.9 kg/m(2)), and 12% were obese (BMI >or= 30 kg/m(2)). Three major dietary patterns were identified: mixed pattern when all food groups and items had about the same factor loading, except for rice and beans; one pattern that relies mainly on rice and beans, which was called a traditional diet; and a third pattern, termed a Western diet, where fat (butter and margarine) and added sugar (sodas) showed the highest positive loading and rice and beans were strong negative components. Among men, the Western diet also included deep-fried snacks and milk products with high positive values. The traditional diet was associated with lower risk of overweight/obesity in logistic models adjusted for dieting, age, leisure physical activity, and occupation (13% reduction in men and 14% reduction in women comparing the traditional and Western diets). DISCUSSION: Factors contributing to the effects of the Brazilian traditional diet may include low-energy density, high-dietary fiber content, incorporation of low glycemic index foods such as beans, or a relatively low food variety. PMID- 11786601 TI - Metabolic effects of mental stress during over- and underfeeding in healthy women. AB - OBJECTIVE: To assess the short-term consequences of carbohydrate or fat overfeeding or of food restriction on the metabolic effects of mental stress in healthy lean women. RESEARCH METHODS AND PROCEDURES: The effects of a sympathetic activation elicited by mental stress were evaluated in a group of healthy women after standardized isocaloric feeding (ISO) or after a 3-day overfeeding with 40% excess calories as either carbohydrate overfeeding (CHO OF) or fat overfeeding (FAT OF). Oxygen consumption rate (VO(2)) was measured as an index of energy expenditure, and subcutaneous glycerol concentrations were monitored with microdialysis. The same measurements were performed in another group of healthy women after ISO and after a 3-day period of underfeeding with a protein sparing modified fast (UF). RESULTS: In all conditions, mental stress significantly increased heart rate, blood pressure, plasma norepinephrine and epinephrine concentrations, and VO(2), and produced a nonsignificant increase in subcutaneous glycerol concentrations. CHO OF and FAT OF did not alter the effects of mental stress on VO(2) and subcutaneous glycerol concentrations. In contrast, UF increased basal VO(2) but significantly reduced its stimulation by mental stress. UF also enhanced the increase in subcutaneous glycerol concentrations during mental stress. DISCUSSION: UF reduces the stimulation of energy expenditure and enhances lipolysis during sympathetic activation. These adaptations may be involved in mobilization of endogenous fat while limiting weight loss. In contrast, short-term overfeeding fails to alter the sympathetic control of energy expenditure and lipolysis. PMID- 11786602 TI - Association of lean tissue and fat mass with bone mineral content in children and adolescents. AB - OBJECTIVES: There has been uncertainty in the adult body composition literature about whether fat mass (FM) or fat free mass is a better predictor of bone mineral content and bone mineral density. This issue has recently also been raised in the pediatric literature. Based on suggested skeletal muscle-bone relationships, this study tested the hypothesis that in children and adolescents lean tissue mass (LTM) is a better predictor of total bone mineral content (TBMC) than is FM. RESEARCH METHODS AND PROCEDURES: Subjects were 133 Italian children and adolescents, 5 to 17 years of age, undergoing a routine medical screen. FM (kilograms), LTM (kilograms), and TBMC (kilograms) were measured by DXA. Multiple regression analyses tested the independent association of FM and LTM with bone mineral content. RESULTS: Regression analyses, adjusting for pubertal status and other covariates, showed that FM and LTM were independently associated with TBMC. These associations were similar for boys and girls. TBMC was more strongly associated with LTM than FM. DISCUSSION: These observations support the hypothesis that in children and adolescents a close association exists between LTM, a measure of skeletal muscle, and skeletal characteristics. PMID- 11786603 TI - Resistin--resistant to defining its role. PMID- 11786604 TI - Research considerations in obesity surgery. PMID- 11786606 TI - Chiral amplification of oligopeptides in two-dimensional crystalline self assemblies on water. AB - Differences in the two-dimensional packing arrangements of racemic and enantiomeric crystalline self-assemblies on the water surface of amphiphilic activated analogs of lysine and glutamic acid have been used to prepare oligopeptides of homochiral sequence and oligopeptides of single handedness from chiral nonracemic mixtures. The crystalline structures on the water surface were determined by grazing incidence x-ray diffraction and the diastereomeric composition of the oligopeptides by matrix-assisted laser desorption time-of flight mass spectrometry with enantio-labeling. These results suggest that reactivity of ordered clusters at interfaces might have played a role in the generation of early homochiral biopolymers. PMID- 11786607 TI - Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. AB - Single-cell mouse embryos were infected in vitro with recombinant lentiviral vectors to generate transgenic mice carrying the green fluorescent protein (GFP) gene driven by a ubiquitously expressing promoter. Eighty percent of founder mice carried at least one copy of the transgene, and 90% of these expressed GFP at high levels. Progeny inherited the transgene(s) and displayed green fluorescence. Mice generated using lentiviral vectors with muscle-specific and T lymphocyte specific promoters expressed high levels of GFP only in the appropriate cell types. We have also generated transgenic rats that express GFP at high levels, suggesting that this technique can be used to produce other transgenic animal species. PMID- 11786608 TI - Emergence of modern human behavior: Middle Stone Age engravings from South Africa. AB - In the Eurasian Upper Paleolithic after about 35,000 years ago, abstract or depictional images provide evidence for cognitive abilities considered integral to modern human behavior. Here we report on two abstract representations engraved on pieces of red ochre recovered from the Middle Stone Age layers at Blombos Cave in South Africa. A mean date of 77,000 years was obtained for the layers containing the engraved ochres by thermoluminescence dating of burnt lithics, and the stratigraphic integrity was confirmed by an optically stimulated luminescence age of 70,000 years on an overlying dune. These engravings support the emergence of modern human behavior in Africa at least 35,000 years before the start of the Upper Paleolithic. PMID- 11786609 TI - Do neurons predict the future? PMID- 11786610 TI - The future of medicine. PMID- 11786612 TI - High-energy physics. Repairs weakened neutrino detector. PMID- 11786611 TI - Clinical trials. Proposed rules aim to curb financial conflicts of interest. PMID- 11786613 TI - Oldest art. From a modern human's brow--or doodling? PMID- 11786614 TI - Evolutionary biology. Finches adapt rapidly to new homes. PMID- 11786615 TI - Endangered species. Fur flies over charges of misconduct. PMID- 11786616 TI - Cancer research. Will bigger mean better for U.K. charity? PMID- 11786617 TI - Asthma research. Missing gene takes mice's breath away. PMID- 11786618 TI - Stem cell research. Stem cells may shore up transplanted hearts. PMID- 11786619 TI - U.S. budget. Spending triples on terrorism R&D. PMID- 11786621 TI - Optics. Crystal stops light in its tracks. PMID- 11786620 TI - Stem cell research. Rat brains respond to embryonic stem cells. PMID- 11786622 TI - Geology. Subtleties of sand reveal how mountains crumble. PMID- 11786623 TI - Bioengineering. Plant scientists see big potential in tiny plastids. PMID- 11786624 TI - American Geophysical Union meeting. Of ocean weather and volcanoes. PMID- 11786625 TI - Women in science. China debates big drop in women physics majors. PMID- 11786626 TI - Brazil. Tough placebo rules leave scientists out in the cold. PMID- 11786627 TI - Science education. U.S. programs ask faculty to help improve schools. PMID- 11786628 TI - Women in science. European strategies for promoting women in science. PMID- 11786629 TI - Astronomy. Putting galaxies on the scale. PMID- 11786630 TI - Proteomics. Integrating interactomes. PMID- 11786631 TI - Genetics. Do X chromosomes set boundaries? PMID- 11786632 TI - Chemistry. A new oxidation state for Pd? PMID- 11786633 TI - Synthetic chemistry. The key to successful organic synthesis is. PMID- 11786634 TI - Cell biology. Slick recruitment to the Golgi. PMID- 11786635 TI - Faithful expression of imprinted genes in cloned mice. PMID- 11786636 TI - Surface stress and thermodynamic nanoscale size selection. AB - Using the Si(111) surface as an example, we show how temperature can be used to tune the size of domains during a surface phase transition. From analysis of the measured stable domain sizes, we determine key material parameters and clarify the close relationship between nucleation and thermodynamic size selection. More generally, the model we developed describes nanoscale self-assembly processes in contact with a reservoir (for example, liquid- or vapor-phase epitaxy). PMID- 11786637 TI - Continuous wave operation of a mid-infrared semiconductor laser at room temperature. AB - Continuous wave operation of quantum cascade lasers is reported up to a temperature of 312 kelvin. The devices were fabricated as buried heterostructure lasers with high-reflection coatings on both laser facets, resulting in continuous wave operation with optical output power ranging from 17 milliwatts at 292 kelvin to 3 milliwatts at 312 kelvin, at an emission wavelength of 9.1 micrometers. The results demonstrate the potential of quantum cascade lasers as continuous wave mid-infrared light sources for high-resolution spectroscopy, chemical sensing applications, and free-space optical communication systems. PMID- 11786638 TI - Synthesis and structure of formally hexavalent palladium complexes. AB - Formally hexavalent palladium complexes have been isolated and structurally characterized for the first time. Thermal condensation reaction of three molecules of 1,2-C6H4(SiH2)2PdII(R2PCH2CH2PR2) (where R is defined as a methyl or ethyl) provided trinuclear palladium complexes. Single-crystal x-ray analysis revealed that each of the central palladium atoms of the complexes is ligated by six silicon atoms and is hexavalent, whereas the other palladium atoms are divalent. PMID- 11786639 TI - Direct determination of the timing of sea level change during termination II. AB - An outcrop within the last interglacial terrace on Barbados contains corals that grew during the penultimate deglaciation, or Termination II. We used combined 230Th and 231Pa dating to determine that they grew 135.8 +/- 0.8 thousand years ago, indicating that sea level was 18 +/- 3 meters below present sea level at the time. This suggests that sea level had risen to within 20% of its peak last interglacial value by 136 thousand years ago, in conflict with Milankovitch theory predictions. Orbital forcing may have played a role in the deglaciation, as may have isostatic adjustments due to large ice sheets. Other corals in the same outcrop grew during oxygen isotope (delta18O) substage 6e, indicating that sea level was 38 +/- 5 meters below present sea level, about 168.0 thousand years ago. When compared to the delta18O signal in the benthic V19-30/V19-28 record at that time, the coral data extend to the previous glacial cycle the conclusion that deep-water temperatures were colder during glacial periods. PMID- 11786640 TI - Iron-silicon alloy in Earth's core? AB - We have investigated the phase relations in the iron-rich portion of the iron silicon (Fe-Si) alloys at high pressures and temperatures. Our study indicates that Si alloyed with Fe can stabilize the body-centered cubic (bcc) phase up to at least 84 gigapascals (compared to approximately 10 gigapascals for pure Fe) and 2400 kelvin. Earth's inner core may be composed of hexagonal close-packed (hcp) Fe with up to 4 weight percent Si, but it is also conceivable that the inner core could be a mixture of a Si-rich bcc phase and a Si-poor hcp phase. PMID- 11786641 TI - Sex-biased hatching order and adaptive population divergence in a passerine bird. AB - Most species of birds can lay only one egg per day until a clutch is complete, and the order in which eggs are laid often has strong and sex-specific effects on offspring growth and survival. In two recently established populations of the house finch (Carpodacus mexicanus) in Montana and Alabama, breeding females simultaneously adjusted the sex and growth of offspring in relation to their position in the laying order, thereby reducing the mortality of sons and daughters by 10 to 20% in both environments. We show experimentally that the reduction in mortality is produced by persistent and sex-specific maternal effects on the growth and morphology of offspring. These strong parental effects may have facilitated the rapid adaptive divergence among populations of house finches. PMID- 11786642 TI - Unique and redundant connexin contributions to lens development. AB - Connexin genes encode intercellular channels that help to coordinate development. In mice, the targeted deletion of different connexins produces disparate effects on ocular growth and differentiation in the lens, and the need for multiple channel subunits is poorly understood. Knockout of Cx46 causes a loss of homeostasis and cataracts. Deletion of Cx50 results in reduced ocular growth and cataracts. Targeted replacement of Cx50 with Cx46 by genetic knock-in corrected defects in cellular differentiation and prevented cataracts, but did not restore normal growth. These data show that intrinsic properties of Cx50 were required for cellular growth, whereas nonspecific restoration of communication by Cx46 maintained differentiation. PMID- 11786643 TI - Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. AB - Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma. PMID- 11786644 TI - Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. AB - T-bet is a member of the T-box family of transcription factors that appears to regulate lineage commitment in CD4 T helper (TH) lymphocytes in part by activating the hallmark TH1 cytokine, interferon-gamma (IFN-gamma). IFN-gamma is also produced by natural killer (NK) cells and most prominently by CD8 cytotoxic T cells, and is vital for the control of microbial pathogens. Although T-bet is expressed in all these cell types, it is required for control of IFN-gamma production in CD4 and NK cells, but not in CD8 cells. This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage. PMID- 11786645 TI - Stage-specific transcription of distinct repertoires of a multigene family during Plasmodium life cycle. AB - Members of a multigene family in the rodent malaria parasite Plasmodium yoelii yoelii code for 235-kilodalton proteins (Py235) that are located in the merozoite apical complex, are implicated in virulence, and may determine red blood cell specificity. We show that distinct subsets of py235 genes are expressed in sporozoites and hepatic and erythrocytic stages. Antibodies to Py235 inhibited sporozoite invasion of hepatocytes. The switch in expression profile occurred immediately after transition from one stage to another. The results suggest that this differential expression is driven by strong biological requirements and provide evidence that hepatic and erythrocytic merozoites differ. PMID- 11786646 TI - Safety considerations of DNA in food. AB - Recombinant DNA techniques are capable of introducing genetic changes into food organisms that are more predictable than those introduced through conventional breeding techniques. This review discusses whether the consumption of DNA in approved novel foods and novel food ingredients derived from genetically modified organisms (GMOs) can be regarded as being as safe as the consumption of DNA in existing foods. It concludes that DNA from GMOs is equivalent to DNA from existing food organisms that has always been consumed with human diets. Any risks associated with the consumption of DNA will remain, irrespective of its origin, because the body handles all DNA in the same way. The breakdown of DNA during food processing and passage through the gastrointestinal tract reduces the likelihood that intact genes capable of encoding foreign proteins will be transferred to gut microflora. The review does not specifically address food safety issues arising from the consumption of viable genetically modified microorganisms but it shows that the likelihood of transfer and functional integration of DNA from ingested food by gut microflora and/or human cells is minimal. Information reviewed does not indicate any safety concerns associated with the ingestion of DNA per se from GMOs resulting from the use of currently available recombinant DNA techniques in the food chain. PMID- 11786647 TI - Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation. AB - Adverse effects of high vitamin B(6) intake include peripheral neuropathy. Recent studies focussing on the reduction of plasma homocysteine as a risk factor for vascular disease showed that vitamin B(6) reduces plasma folate levels. The significance of this finding is unclear. We therefore analyzed plasma folate and basal homocysteine levels as well as the response to an oral methionine loading test in 8 healthy individuals before and after a controlled supplementation with oral doses of 25 mg pyridoxine for 10 days. Plasma pyridoxal phosphate increased from 40.6 +/- 13.6 to 426.8 +/- 200.3 nmol/l (p < 0.001), whereas plasma folate decreased from 6.3 +/- 1.6 to 4.6 +/-1.5 ng/ml (p < 0.01), respectively. Plasma vitamin B(12) and basal homocysteine levels remained unchanged (234.0 +/- 27.8 vs. 217.1 +/- 50.4 pg/ml and 10.9 +/- 4.8 vs. 10.1 +/- 3.6 micromol/l). There was no significant effect of vitamin B(6) supplementation on the area under methionine and homocysteine concentration versus time curve. Significant correlations were found between pre- and post-supplement levels of folate as well as PLP levels (r = 0.73, p < 0.05; r = 0.75, p < 0.05). These data suggest that a dose of 25 mg vitamin B(6) supplemented for 10 days reduces plasma folate but did not affect basal and postprandial homocysteine levels suggesting (1) a normal cellular availability of folate or (2) a compensation of impaired homocysteine remethylation by increased transsulfuration. PMID- 11786648 TI - Fat-soluble vitamin status is not affected by diacylglycerol consumption. AB - OBJECTIVE: The objective of this study was to examine the effect of dietary diacylglycerol (DAG) on the bioavailability of fat-soluble vitamins in comparison with triacylglycerol (TAG). METHODS: We conducted a long-term administration test of DAG and TAG in 27 healthy men aged 27-47 years. After measuring baseline values, subjects were randomized into two groups, one group (n = 15) was given DAG and the other (n = 12) was given TAG. Subjects ingested 20 g of DAG or TAG either in mayonnaise or an emulsion drink of their own choice at meals once a day for 12 weeks. At 4, 8 and 12 weeks, fasting blood samples were drawn and serum levels of vitamin A, E, and D were measured. RESULTS: There were no significant changes in vitamin A levels throughout the study period. Compared to the initial values (using a Student's t test for paired values), significant differences of vitamin E and D were seen at some points during the experiment. According to a two-way repeated measures analysis of variance, however, DAG and TAG (lipid) and time had no effect on fat-soluble vitamin levels. CONCLUSIONS: Our results indicate that DAG does not affect the absorption of the fat-soluble vitamins in diets. PMID- 11786649 TI - Fat-soluble vitamins in the maternal diet, influence of cod liver oil supplementation and impact of the maternal diet on human milk composition. AB - BACKGROUND/AIMS: To investigate lactating mothers' intake of fat-soluble vitamins in free-living subjects and to what extent cod liver oil supplementation influences the maternal intake in a population with common intake of cod liver oil. The impact of maternal diet on the concentration of fat-soluble vitamins in human milk was studied. METHODS: Dietary intake of 77 lactating women was investigated by 24-hour diet recalls and breast-milk samples were taken at the same occasions. Breast milk samples were analyzed for fat-soluble vitamins. RESULTS: The median intakes were 927 microg/day for vitamin A, 5.5 mg/day for vitamin E and 3.3 microg/day for vitamin D. Maternal vitamin A, E and D intakes were higher when the diet was supplemented with cod liver oil. Icelandic breast milk was found to have high contents of vitamin A and E. Only vitamin D was too low in breast milk to meet the recommended intake for infants. Retinylpalmitate in relation to lipids correlated with maternal vitamin A intake (r = 0.23, p < 0.05). The group with cod liver oil supplementation had significantly lower levels of gamma-tocopherol in breast milk (p < 0.01), whereas the supplementation did not affect other fat-soluble vitamins. CONCLUSION: The recommended intake of fat-soluble vitamins for lactating women can more easily be met with a cod liver oil supplementation than diet alone. Only vitamin D in human milk cannot meet the recommended intakes for infants, with normal breastfeeding. There is a relationship between the content of vitamins A and E in human milk and the maternal diet. PMID- 11786650 TI - Estimation of dietary fat intake of Belgian pregnant women. Comparison of two methods. AB - AIM: To evaluate the validity and usefulness of a food frequency questionnaire (FFQ) which was designed to evaluate individual fat consumption for a Dutch population relative to 7-day estimated records (7d ER). The FFQ has been validated previously and was adapted to the Belgian situation. METHODS: Longitudinal study in 26 healthy pregnant women; FFQ and 7d ER were obtained during the 1st and 3rd trimesters. RESULTS: FFQ was validated with 7d ER. Fat and fatty acid intake estimated by the FFQ did not differ significantly (p < 0.01) from data obtained by the 7d ER except for 18:2n-6. Pearson correlation coefficient between the 2 methods ranged from 0.62 to 0.68. On average, 47% of the women were classified in the same quartile with the 2 methods and less than 2% in the opposite quartile. Total fat intake, calculated from FFQ, was on average 87.9 (SD 18.1) g/day. The mean intake of linoleic acid was 13.3 (SD 5.4) g/day and of alpha-linolenic acid was 1.4 (SD 0.5) g/day. The dietary intake of the saturated, monounsaturated and polyunsaturated fatty acids was respectively 34.7 (SD 10.0) g/day, 29.6 (SD 8.1) g/day and 15.7 (SD 5.9) g/day. CONCLUSION: The FFQ gives similar results for fat intake as the 7d ER and is thus considered an appropriate method for classifying individuals to the right part of the distribution of dietary fat intake. PMID- 11786651 TI - Supplementation of Areca catechu L. extract alters triglyceride absorption and cholesterol metabolism in rats. AB - Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on triglyceride absorption in triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of triglyceride and the plasma lipid concentration. The absorbed triglyceride that appeared in the blood after an oral dose of [9,10(n)-(3)H] triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group. The hepatic and intestinal ACAT (acyl CoA:cholesterol acyltransferase) activities were significantly decreased in the Areca group compared with the control group. Hence, further studies are needed to elucidate the structure and chemical properties of the active compound in the water-soluble Areca extract that lowers cholesterol absorption. PMID- 11786652 TI - A sucrose-rich diet during pregnancy causes a similar response in Sprague-Dawley and Wistar rats. AB - BACKGROUND/AIMS: In order to determine whether the response to a sucrose-rich diet (SRD) during pregnancy in the rat varies depending on the strain, the responsiveness to a SRD (63 g sucrose/100 g) during pregnancy in Wistar and Sprague-Dawley rats was studied. METHODS: One group of rats of each strain was fed the SRD, whereas another group received the same diet except that sucrose was replaced by an equal amount of cornstarch. Half of the rats were mated, and all animals were studied 20 days later. RESULTS: Initial body weight did not differ among groups, but final body weight of pregnant Wistar rats was lower than in Sprague-Dawley, and this difference corresponded to a decrease in fetal body weight in the former. Feeding a SRD did not modify pregnancy outcome in either rat strain. Plasma triglycerides increased with a SRD, although this effect was milder in Wistar pregnant rats than in the other groups. Adipose tissue lipoprotein lipase activity was lower in pregnant than in virgin rats, but no differences were found as result of either diet or rat strain. Liver triglyceride concentration increased in virgin rats fed SRD, the effect being greater in Sprague-Dawley than in Wistar rats. CONCLUSION: Differences in the response to a SRD in pregnant and virgin rats do not depend on the strain of rats used. PMID- 11786653 TI - Comparative pharmacokinetics of three preparations of the new antifungal SPK-843. AB - The pharmacokinetics and tissue distribution of three preparations of SPK-843 (N dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure, were compared in rats after a single 1.25 mg/kg intravenous administration. Blood and tissue samples were obtained at 0.25-96 h after injection. The serum pharmacokinetics of the three dosage forms of the antibiotic, A (5% glucose solution), B (10% lipid emulsion at pH 5.3) and C (10% lipid emulsion at pH 7.5), did not show large differences, the half-lives being 22.2, 26.5 and 23.2 h and the AUC(0-infinity) 35.5, 40 and 44.8 microg.h.ml(-1) for preparations A, B and C, respectively. The tissue uptake of the two lipid-based preparations, particularly the spleen uptake, was greater than that of the glucose preparation, suggesting an active role of the lipid vehicle in tissue distribution. PMID- 11786654 TI - Antimicrobial resistance surveillance of gram-negative bacteria isolated from intensive care units of four different hospitals in Turkey. Evaluation of the prevalence of extended-spectrum and inducible beta-lactamases using different E test strips and direct induction methods. AB - BACKGROUND: The aim of this study was to determine the antimicrobial resistance of gram-negative rods (GNRs) isolated from surgical intensive care units and to establish the prevalence of extended-spectrum beta-lactamases (ESBLs) and inducible beta-lactamases (IBLs). We also wished to determine the widespread beta lactam substrate in ESBL-positive GNRs by two different E-test strips and to discuss the value of the routine utilization of these substrates together. METHODS: Out of 348 nosocomial gram-negative strains isolated with similar methods, 236 strains with resistance to the beta-lactam group of antimicrobials using the E-test method were included in this study. Two different strips were used for the detection of ESBLs: cefotaxime/cefotaxime + clavulanic acid (CT/CTL) and ceftazidime/ceftazidime + clavulanic acid (TZ/TZL). For IBLs, the double-disk method was used. RESULTS: The order of frequency of the strains, starting with the most frequent, was Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. In the 236 strains, the ESBL positivity rate was found to be 19.5% with TZ/TZL and CT/CTL strips, while it was 13.2% for IBL in 348 strains. Seventy one percent of ESBL-positive strains gave parallel results with TZ/TZL and CT/CTL. ESBL positivity with only TZ/TZL or only CT/CTL was found to be 18 and 8%. CONCLUSIONS: Our study showed that except for imipenem, amikacin and ciprofloxacin, there was a high resistance to other antimicrobials, and multiresistance rates were increased in the strains in which ESBLs and IBLs were detected. In particular, the increasing prevalence of ESBLs in K. pneumoniae and IBLs in P. aeruginosa emphasizes the importance of the problem of infection control and antibiotic administration policies. Although it was seen that the prevalence of substrate templates in the detection of ESBL positivity was similar, we think that it is more useful to use two different strips together to obtain precise results. PMID- 11786655 TI - Differences between two new quinolones (gemifloxacin and trovafloxacin) and ciprofloxacin in their concentration-dependent killing of Streptococcus pneumoniae. AB - BACKGROUND: Ciprofloxacin resistance influences the in vitro effect of new quinolones on Streptococcus pneumoniae. METHODS: The early (over 3 h) in vitro bactericidal activity of gemifloxacin, trovafloxacin and ciprofloxacin was explored by time-kill tests against two ciprofloxacin-susceptible (MIC = 0.5 and 1 microg/ml) and two ciprofloxacin-resistant (MIC = 16 microg/ml) S. pneumoniae strains. RESULTS: At subinhibitory concentrations (0.5 x MIC) and inhibitory concentrations (1 x MIC), only gemifloxacin exhibited significant bactericidal activity with, respectively, approximately 85 and approximately 95% decrease in the initial inoculum of the two ciprofloxacin-resistant strains. At concentrations similar to peak serum concentrations (1.5, 3 and 2.5 microg/ml for gemifloxacin, trovafloxacin and ciprofloxacin, respectively) after standard doses, only gemifloxacin exhibited an approximately 99.9% (3 log(10)) reduction in the initial inoculum for the four strains tested, regardless of their susceptibility to ciprofloxacin. No bactericidal activity was exhibited for the other two quinolones against the ciprofloxacin-resistant strains. CONCLUSIONS: Gemifloxacin offers high early bactericidal activity at concentrations similar to peak and trough levels, theoretically preventing regrowth over the dosing interval, and thus dealing with the problem of ciprofloxacin resistance in S. pneumoniae. PMID- 11786656 TI - Resistance to vancomycin, LY333328, ciprofloxacin and trovafloxacin of community acquired and nosocomial strains of Enterococcus faecalis isolated in Badajoz (Spain) with and without high-level resistance to streptomycin and gentamicin. AB - In vitro resistance of community-acquired and nosocomial strains of Enterococcus faecalis isolated in Badajoz (Spain) were determined by a microdilution method. The isolates were identified with conventional MicroScan Pos Combo 4 I dehydrated panels. No resistance to glycopeptides was found, but LY333328 was 2-4 times more active than vancomycin. In the nosocomial strains, high-level resistance to streptomycin (HLRS) was 54.7%, and high-level resistance to gentamicin (HLRG) was 38.1%. Resistance to ciprofloxacin and trovafloxacin was 45.3 and 38.9%, respectively. In the community-acquired isolates, HLRS, HLRG, resistance to ciprofloxacin and resistance to trovafloxacin were 44.2, 17.3, 15.4 and 13.5%, respectively. Trovafloxacin was 2-4 times more active than ciprofloxacin against both groups of strains. An association between high-level resistance to aminoglycosides and resistance to fluoroquinolones was noted. The resistance to aminoglycosides did not influence the activity of vancomycin and LY333328. PMID- 11786657 TI - Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia. AB - BACKGROUND AND METHODS: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. RESULTS: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. CONCLUSION: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia. PMID- 11786658 TI - In vitro models of a three-drug regimen (epirubicin, cisplatin and fluorouracil) for the treatment of colorectal cancer. AB - The activity of epirubicin, cisplatin and 5-fluorouracil (5-FU), as single agents or in combination (ECF), was investigated in three human colon cancer cell lines by two different assays (cell-counting assay and sulforhodamine B assay) in vitro. 5-FU was tested with both short and continuous exposure. Particular interest was focused on the results obtained in the HCT8-FU cell line, a subline with experimentally induced resistance to 5-FU. The positive modulation of both cisplatin and epirubicin cytotoxicity by 5-FU makes the ECF regimen an attractive protocol for combination therapy in colorectal cancer. PMID- 11786659 TI - Epirubicin, cisplatin and continuous-infusion 5-fluorouracil (ECF regimen) in the treatment of advanced colorectal cancer. AB - Thirty-one patients with advanced colorectal cancer were treated with a regimen of epirubicin, cisplatin and continuous-infusion (c.i.) 5-fluorouracil (5-FU) (ECF regimen). Twenty-seven patients were evaluable for response rate (RR), progression-free survival (PFS) and overall survival (OS). In this study, the ECF chemotherapy yielded a 51% RR with a PFS of more than 8 months, an OS of more than 11 months and tolerable toxicity. In spite of the perplexity concerning the use of anthracyclines in colorectal cancer, the ECF regimen seems to be a possible treatment even for this malignancy. Controlled studies with ECF versus standard treatments and versus 5-FU alone in c.i. are necessary. PMID- 11786660 TI - Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. AB - We have previously reported that long-term treatment with clarithromycin (CAM) increased the median survival of patients with non-small cell lung cancer, and improved various clinical parameters in these patients. In the present study, CAM was administered to 33 patients with unresectable primary non-small cell lung cancer, who had received chemotherapy, radiotherapy or both (basic cancer therapy). Patients with clinical backgrounds matched to the CAM group, who did not receive CAM treatment, were included into this study as a control group (non CAM group). CAM treatment was initiated 4 weeks after the basic cancer therapy. The non-CAM group did not receive a placebo. Before and after the 3-month treatment with CAM, body weight, serum levels of interleukin-6 (IL-6, a cytokine which, together with TNF-alpha, plays a crucial role in the development of cancer cachexia), total protein, albumin, cholinesterase and hemoglobin were measured for the evaluation of the patients' clinical status. There were no statistically significant differences in serum levels of IL-6 between the CAM group before the treatment and the non-CAM group. After 3 months of CAM treatment, serum levels of IL-6 significantly decreased. In contrast, body weight, cholinesterase, and hemoglobin increased to a significant extent. Among these four parameters, however, the decrease in serum IL-6 levels was only statistically correlated with the increase in body weight, but not with that in other parameters. Furthermore, CAM-treated patients whose serum IL-6 levels were decreased after 3 months of treatment survived longer: there was a statistically significant correlation between the decrease in serum IL-6 and survival time. In contrast, in the non-CAM group, these parameters did not change significantly during the study. These results suggest that CAM may reduce the progression of cancer-associated cachexia. PMID- 11786661 TI - Medical treatment of primary biliary cirrhosis and primary sclerosing cholangitis. AB - Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming. PMID- 11786662 TI - Young patients with Barrett's oesophagus experience less reflux complaints. AB - BACKGROUND/AIM: Barrett's oesophagus can be expected to be more resistant to the effects of acidic refluxate, and, hence, it can be postulated that patients with Barrett's oesophagus experience less reflux complaints. A cross-sectional study in consecutive patients presenting with Barrett's oesophagus and reflux oesophagitis was done in order to test this hypothesis. METHODS: Patients received a standardized questionnaire, and overall and specific symptom scores were assessed on a five-point Likert scale. RESULTS: Reflux oesophagitis was diagnosed in 128 patients and Barrett's oesophagus in 42. Patients with reflux oesophagitis had statistically significantly higher symptom scores than patients with Barrett's oesophagus (mean +/- SD): 9.1 +/- 6.3 vs. 6.2 +/- 5.4 (p = 0.01). The scores for heartburn and acid regurgitation were significantly higher in reflux oesophagitis, while there was a trend for epigastric pain, retrosternal pain, and vomitus. The symptom scores of patients with Barrett's oesophagus older than 60 years were not different from patients with reflux oesophagitis older than 60 years: 5.2 +/- 4.8 vs. 7.4 +/- 6.4. However, the symptom scores of patients younger than 60 years were significantly higher in those with reflux oesophagitis: 10.2 +/- 5.7 vs. 7.2 +/- 5.7 (p = 0.04). Odynophagia, heartburn, and acid regurgitation scored significantly higher in patients with reflux oesophagitis younger than 60 years as compared with Barrett patients younger than 60 years. CONCLUSIONS: Patients with Barrett's oesophagus indeed suffer less from reflux complaints. However, this is only true for those younger than 60 years. PMID- 11786663 TI - Potent and long-lasting action of lafutidine on the human histamine H(2) receptor. AB - BACKGROUND/AIM: Based on animal models, lafutidine, a novel histamine H(2) receptor (H(2)R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H(2)R-mediated effects. However, no reports have been published concerning its direct interaction with the human H(2)R. This study aims at characterizing its interaction with human H(2)R. METHODS: Chinese hamster ovary cell lines stably expressing human H(2)Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [(3)H]tiotidine binding and histamine stimulated cAMP production were analyzed. The effects of preincubation with 2.78 x 10(-7) M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [(3)H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the C(max) of lafutidine (10 mg p.o.) and above the C(max) of famotidine (20 mg p.o.). RESULTS: Lafutidine inhibited [(3)H]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. CONCLUSION: Lafutidine shows a potent and long lasting antagonism on the human H(2)R. PMID- 11786664 TI - The fine form of Helicobacter pylori on the metaplastic duodenal mucosa is associated with recurrent duodenal ulcers. AB - BACKGROUND/AIM: It is well known that Helicobacter pylori changes its shapes according to various environmental conditions. The aim of this study was to examine the morphological differences between H. pylori in the duodenum and that in the stomach. METHODS: Duodenal biopsy specimens were obtained from patients with duodenal mucosal lesions, and these specimens were then histopathologically examined. Morphological and genetic properties of cultured H. pylori isolates were analyzed. RESULTS: H. pylori was identified in 16 out of 50 duodenal biopsy specimens. Along with the regular form, we found a fine form of H. pylori in the gastric metaplastic mucosa of ten duodenal specimens that was shorter in length and thinner in diameter than the regular helical form. There were no detectable differences between the ureA-ureB polymorphism of the duodenal fine form and that of gastric regular form in a single patient. As compared with patients without H. pylori in the duodenum, the prevalence of recurrent duodenal ulcers significantly increased in patients with the fine form (p < 0.05), but not in patients with the regular form. CONCLUSION: The fine form of H. pylori in the metaplastic duodenal mucosa could result from its adaptation to the duodenal environment and may be associated with the recurrence of a duodenal ulcer. PMID- 11786665 TI - Mechanisms of lectin (phytohemagglutinin)-induced growth in small intestinal epithelial cells. AB - BACKGROUND/AIMS: The lectin phytohemagglutinin is a mitogen for intestinal epithelial cells in vivo. The mechanisms of action are unknown and were therefore analyzed in vitro. METHODS: Human (Intestine-407) and rat (IEC-6; IEC-18) intestinal epithelial cell lines were stimulated with phytohemagglutinin. Proliferation was assayed by (3)H-thymidine incorporation, activation of mitogen activated protein kinase (MAPK) by Western blotting, and induction of c-fos mRNA expression by semiquantitative polymerase chain reaction. Control experiments were performed with phenyl-N-acetyl-alpha-D-galactosaminide or the tyrosine kinase inhibitor tyrphostin A25. RESULTS: Phytohemagglutinin (0.1 microg/ml) significantly stimulated proliferation in all three cell lines after 48-72 h. MAPK activation was detected after 15-30 min, and an induction of c-fos mRNA expression after 15- 30 min of stimulation. Mitogenic effects were blocked by preincubation with phenyl-N-acetyl-alpha-D-galactosaminide or tyrphostin A25. CONCLUSION: Phytohemagglutinin stimulated proliferation, MAPK activation and induction of c-fos mRNA expression. The lectin may contribute to intestinal mucosal growth and regeneration thereby preventing gut atrophy. PMID- 11786666 TI - Effects of berberine on intracellular free calcium in smooth muscle cells of Guinea pig colon. AB - AIM: To investigate the effects and mechanism of berberine (Ber) on the intracellular free calcium concentration ([Ca(2+)](i)) in the smooth muscle cells of guinea pig colon. METHODS: The changes of [Ca(2+)](i) were assayed by the biwavelength spectrophotometry with Fura 2-AM in the cell suspension of the smooth muscle cells, which were freshly isolated from guinea pig colon. RESULTS: In the resting state, [Ca(2+)](i) in the HEPES-Ringer solution (CaCl(2) 1.5 mmol.l(-1)) was (108 +/- 9.4) nmol.l(-1) (n = 7). Ber had no significant effects on the resting [Ca(2+)](i), but markedly inhibited the increase in [Ca(2+)](i )induced by 60 mmol.l(-1) KCl in a concentration-dependent manner. The value of IC(50 )was 34.09 micromol.l(-1). 30 and 100 micromol.l(-1) Ber also inhibited the elevation of [Ca(2+)](i) evoked by 10 micromol.l(-1) Ach in a dose-dependent fashion in the presence or absence of extracellular Ca(2+). In addition, Ber inhibited the elevation of [Ca(2+)](i) stimulated by cyclopiazonic acid (CPA) in a dose-dependent manner. This effect was more potent in the HEPES-Ringer solution (IC(50) = 37.79 micromol.l(-1)) than Ca(2+)-free medium (IC(50) = 49.70 micromol.l(-1)). CONCLUSIONS: Ber possessed an inhibitory effect on the influx of extracellular Ca(2+) and Ca(2+)-release from intracellular stores in the smooth muscle cells of colon. That is to say Ber may be a blocker of Ca(2+) channels. PMID- 11786667 TI - Effect of electrical stimulation on acupuncture points in diabetic patients with gastric dysrhythmia: a pilot study. AB - BACKGROUND/AIMS: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. METHODS: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects' legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured. RESULTS: There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 +/- 19.38% vs. 45.93 +/- 19.72 and 48.92 +/- 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 +/- 27.64 vs. 73.11 +/- 22.37 pmol/l; p < 0.05). CONCLUSIONS: The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients. PMID- 11786668 TI - Sensory and biomechanical responses to distension of the normal human rectum and sigmoid colon. AB - BACKGROUND: Visceral pain is a major clinical problem. The aim of the present study was to compare the pain and biomechanical responses to standardized distension of the human colon. METHODS: The relation between pain intensity and pressure, cross-sectional area (CSA) and tension-strain relations of the rectum and sigmoid colon were studied in 11 normal subjects following standardized distension using impedance planimetry. The bag was inflated stepwise with pressures up to 6 kPa. The subjects, who were blinded for the distension procedure, rated their pain intensity using an aggregate visual analogue score (VAS) combining the intensity of the feeling of air, urge to defecate and pain. RESULTS: The distensions produced an initial rapid increase in CSA followed by a phase of slow increase until a steady state CSA was reached after 0.5-1 min. Several phasic contractions (observed as short-term decreases in the CSA) were recorded in the rectum from the end of the rapid phase to the end of distension at pressures from 1 to 5 kPa. The CSA in the rectum and sigmoid colon was 3,706 +/- 426 mm(2) and 2,305 +/- 426 mm(2) at the maximum bag pressure of 6 kPa (F = 52.4, p < 0.001). The tension-strain relation did not differ between the normal rectum and sigmoid colon. The VAS score for every modality (air, defecation and pain) revealed an increase in intensity as a function of pressure. The VAS score in the rectum and the sigmoid colon as a function of tension and strain did not show any differences. CONCLUSIONS: The biomechanical properties in the sigmoid colon and rectum were alike. For a given wall tension and circumferential strain the sensibility seems equal in the rectum and the sigmoid colon. The observed difference in perception between the two segments was related to the greater CSA in the rectum. PMID- 11786669 TI - Epidemiological aspects of irritable bowel syndrome in Europe and North America. AB - The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription. PMID- 11786670 TI - Importance of individual response in symptom score evaluation. AB - In making treatment decisions for patients with benign prostatic hyperplasia (BPH), physicians have to rely on the efficacy data published in the literature and adapt this to individual patient's needs. Criticism can be made, however, of the randomised clinical trials (RCTs) that are performed, as the patients enrolled are not an adequate reflection of the general patient population. Although internal validity is high in RCTs with regard to inclusion criteria, external validity is reduced. Another failing of RCTs is the way in which patients are assessed. Typically in many studies, symptom improvement is expressed as a percentage of the Symptom Index improvement. This can be misleading if the results of two trials are compared as this value depends on the pre-treatment Symptom Index. Other methods of evaluation should be considered, such as the presentation of direct symptom outcomes (threshold improvement), the cumulative frequency distribution of threshold improvements or linear regression analysis of individual IPSS. All of these means of expressing the results focus clinical evaluation on the patient himself. PMID- 11786671 TI - Long-term aspects of medical treatment of BPH. AB - Acute urinary retention (AUR) is an important complication of benign prostatic hyperplasia (BPH) and can affect 0.4-25% of men seen in urological practice each year. AUR is also one of the main indications for surgery, being the presenting features of 25-30% of transurethral resection of the prostate (TURP). However, TURP conducted under these conditions is associated with higher morbidity. A number of risk factors for AUR have been identified including severity of LUTS, reduced peak flow rate, prostate volume, post-void residual volume (PVR) and old age. Medical therapy for BPH can impact on prostate size, increased PVR and previous AUR episodes. Finasteride has been shown to reduce prostate size and consequently reduce the risk of AUR. Studies on the alpha(1) blocker, alfuzosin, also report a reduced incidence of AUR compared with placebo. In addition, alfuzosin has proven effective in a trial without catheter in patients with AUR, thus potentially reducing the need for prostate surgery or allowing elective surgery to be conducted without preoperative catheterisation. Both options are highly beneficial to the patient. PMID- 11786672 TI - Quality of life and sexuality: methodological aspects. AB - Benign prostatic hyperplasia (BPH) can impact significantly on a patient's quality of life (QOL), including sexual functioning. With increased life expectancy, this aspect of the disease is becoming increasingly important. Symptom severity can be measured using a number of instruments, the most common one being the International Prostate Symptom Score (IPSS). A number of studies have shown that symptom severity is correlated with decreased QOL, i.e. the more severe the symptoms, the greater the impact on QOL. Specific questionnaires have been developed to address the issue of sexual function, including the Brief Sexual Function Inventory and the International Index of Erectile Function. Importantly, these instruments can usefully be applied to assess the effect of the various therapies for BPH on sexual function. In general, the alpha(1) blockers have minimal impact on sexual function, compared with finasteride, which can affect libido, ejaculation and erectile function itself. PMID- 11786673 TI - Introduction. PMID- 11786674 TI - Potential mechanisms of action of superselective alpha(1)-adrenoceptor antagonists. AB - This paper reviews the role of alpha(1)-adrenoceptors (ARs) in the aetiology of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). alpha(1)-ARs have been demonstrated to be present and functionally active in the human prostate where the alpha(1A)-AR subtype is involved in the contraction of smooth muscle resulting in dynamic obstruction and related voiding symptoms. Recently there is increasing evidence that extra-prostatic alpha(1)-ARs may also contribute to the development of LUTS/BPH. It appears that alpha(1)-ARs are also present in the human detrusor where the alpha(1D)-AR subtype predominates and potentially plays a role in storage symptoms. This is supported by data from the rat indicating a shift in alpha(1)-AR subtype expression from alpha(1A) to alpha(1D )following surgical obstruction. Furthermore, facilitatory alpha(1)-ARs have been detected in peripheral ganglia of animals where activation of these receptors induced bladder contractions and related storage symptoms. Recent research has also detected alpha(1)-ARs in the human spinal cord with a predominance of the alpha(1D)-AR subtype. Animal studies suggest that alpha(1) ARs in the spinal cord induce bladder contractions by activation of parasympathetic neurons. It may be concluded that voiding symptoms may be related to alpha(1A)-AR mediated smooth muscle contraction in the prostate inducing the dynamic component of obstruction. Storage symptoms may be due to bladder wall hypertrophy secondary to obstruction and/or directly to detrusor instability mediated by alpha(1D)-ARs in the detrusor smooth muscle. alpha(1)-ARs in the spinal cord and/or peripheral ganglia may however also be involved. Since there may be an increase in vascular alpha(1B)-AR subtype expression with ageing it is suggested that blockade of this receptor should be avoided in elderly patients with LUTS/BPH, with the objective of minimising interference with blood pressure regulation. Treatment with superselective alpha(1A)/alpha(1D)-AR-antagonists such as tamsulosin may be indicated to reduce obstruction and both voiding and storage symptoms with minimal risk of cardiovascular side effects, thus it may be considered a first-line medical treatment option in men with LUTS suggestive of BPH. PMID- 11786675 TI - Lower urinary tract symptoms: what are the implications for the patients? AB - Patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) complain about symptoms such as weak stream, dribbling, intermittency, frequency, nocturia and urgency. To effectively manage these symptoms, it is important to better understand the epidemiology and/or the bothersomeness of these symptoms, the impact of the symptoms on the patient's quality of life and life style, when and why patients seek medical advice and the subsequent management of LUTS/BPH in clinical practice. This paper gives an overview of these issues considering 3 recently conducted European surveys. Although voiding symptoms are more frequent in patients with LUTS/BPH, storage symptoms, such as frequency, urgency, nocturia and urge incontinence, seem to be more bothersome to the patients. LUTS seem to have a negative impact on the patient's quality of life and sexuality and to interfere strongly with daily life activities. With regard to sexuality, interference with the patient's overall sex life and erection problems is experienced as much more bothersome than ejaculation problems. After the initial symptoms, most patients postpone a visit to the physician and try to adjust their life style to self manage their symptoms. Eventually they seek medical advice because they are too much bothered by their LUTS. In Italy, medical therapy is the most frequently administered treatment option by urologists (57% of patients) followed by surgery (37% of patients). alpha(1)-Adrenoceptor antagonists are the predominant medical therapy prescribed (70% of all medically treated patients), particularly tamsulosin (35% of all medically treated patients). An interview with European urologists confirms that alpha(1)-adrenoceptor antagonists, especially newer uro-selective ones like tamsulosin, are a very appropriate initial treatment choice in the management of both voiding and storage LUTS. PMID- 11786676 TI - Initial choices and final outcomes in lower urinary tract symptoms. AB - Management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) requires careful thought so that the most appropriate treatment can be targeted to each individual patient. Initial choices in the management of LUTS/BPH include watchful waiting, medical therapies and surgical interventions. A decision on treatment choice should be taken together with the patient. It should be based on the best available scientific evidence but also be individualised to patients' circumstances and personal choices. Management of LUTS/BPH should be focused on the burden and impact of urinary symptoms and related quality of life. The rate of treatment failure, which can be assessed through the switch to other medical therapy or surgery and/or the delay or prevention of complications related to LUTS/BPH, is also important. Beneficial effects of treatment should be balanced against the incidence of adverse events associated with therapy. Medical therapy has been shown to be effective in improving short-term outcomes (maximum urinary flow rate and symptom scores). Increasing evidence indicates that in the long-term more selective alpha(1) adrenoceptor (AR) antagonists such as alfuzosin and tamsulosin may reduce the risk of treatment failure with a comparable rate to finasteride. Although the different alpha(1)-AR antagonists are equivalent in efficacy they differ in tolerability with the subtype selective tamsulosin having the lowest risk for interference with blood pressure regulation. Transurethral resection of the prostate (TURP) improves storage symptoms to a lesser extent and/or more slowly than it improves voiding symptoms. In contrast, alpha(1)-AR antagonists improve both voiding and bothersome storage symptoms to the same extent and quite rapidly which has a considerable impact on quality of life. alpha(1)-AR antagonists also relieve storage symptoms to almost the same extent as TURP. Ultimately the initial choice of treatment will depend upon its efficacy, speed of onset, durability, tolerability and on patients' choice. For the majority of patients with moderate to severe symptoms a subtype selective alpha(1)-AR antagonist such as tamsulosin offers the best current combination of efficacy and tolerability. PMID- 11786677 TI - Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle. AB - In peripheral tissues, corticosteroid hormone action is determined, in part, through the activity of 11beta-hydroxysteroid dehydrogenases (11beta-HSD), two isozymes of which interconvert hormonally active cortisol (F) and inactive cortisone (E). 11beta-HSD type 2 (11beta-HSD2) inactivates F to E in the kidney, whilst 11beta-HSD type 1 (11beta-HSD1) principally performs the reverse reaction activating F from E in the liver and adipose tissue. Alteration in expression of these 11beta-HSD isozymes in peripheral tissues modifies corticosteroid action: loss of 11beta-HSD2 activity in the kidney results in cortisol-induced mineralocorticoid excess, and loss of hepatic 11beta-HSD1 activity improves insulin sensitivity through a reduction in cortisol-induced gluconeogenesis and hepatic glucose output. Conversely, overexpression of 11beta-HSD1 in omental adipose tissue can stimulate glucocorticoid-induced adipocyte differentiation which may lead to central obesity. Patients with hypopituitarism have many clinical features in common with patients with Cushing's syndrome--notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Our hypothesis was that many of these features may be explained by an effect of growth hormone (GH) on the 11beta-HSD isozymes. As assessed by urinary free cortisol/urinary free cortisone ratios and endorsed through in vitro studies, neither GH nor insulin-like growth factor (IGF)-I affect 11beta-HSD2 activity. Patients with acromegaly show a reduction in hepatic-derived metabolites of cortisol/cortisone - levels return to normal when GH concentrations are normalized. Conversely, patients with GH deficiency in the setting of hypopituitarism demonstrate an increased cortisol/cortisone metabolite ratio and reduction in circulating cortisol concentrations in patients on hydrocortisone replacement. Treatment with low-dose GH replacement reverses these abnormalities. These clinical data suggest that GH (and/or IGF-I) inhibits 11beta HSD1 (i.e. E to F conversion) (parallel in vitro studies suggest that IGF-I and not GH inhibits 11beta-HSD1). These findings have important clinical ramifications. Firstly, the GH-mediated increase in cortisol metabolism (mediated via reduced E to F conversion) may precipitate adrenal insufficiency in hypopituitary patients with partial adrenocorticotropic hormone deficiency commencing GH therapy. Secondly, many of the phenotypic features of hypopituitarism can be explained by an alteration in 11beta-HSD1 activity: GH deficiency effectively increases cortisol production in key target tissues including liver and adipose tissue, promoting insulin resistance and visceral adiposity. Thirdly, the reported beneficial effects of GH on cardiovascular risk factors in patients with hypopituitarism may be an indirect effect via alterations in cortisol metabolism. Finally, the GH/IGF-I modulation of cortisol metabolism may underpin the pathogenesis of common diseases such as central obesity and idiopathic osteoporosis. Patients with central obesity but with no evidence of hypopituitarism have relative GH deficiency and it is exciting to speculate that low-dose GH treatment in this group, by inhibiting cortisol generation within omental fat, may offer a novel therapeutic approach. PMID- 11786678 TI - Glucocorticoids, thyroid hormone and growth hormone interactions: implications for the growth plate. AB - Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T(3)). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T(3) regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T(3) during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth. PMID- 11786679 TI - Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. AB - Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of "functional" GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach. PMID- 11786680 TI - Growth abnormalities associated with adrenal disorders and their management. AB - Linear growth can be disturbed in paediatric adrenal disease associated with endocrine hypo- or hyperfunction. Tall stature is a feature in some patients with adrenocorticotropic hormone resistance syndromes and short stature is recognized in the IMAGe (intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies) association. In autoimmune Addison's disease, growth is usually normal. In congenital adrenal hyperplasia, height may be compromised by advanced skeletal maturation or by suppressed growth, particularly in the neonatal period due to excess glucocorticoid treatment. In virilizing adrenal tumours, height is increased at diagnosis, but after surgical cure final height is usually in the normal range. In Cushing's disease, height was abnormally short in 50% of patients at presentation. After successful treatment, spontaneous catch-up growth was not seen. This led to a diagnosis of growth hormone (GH) deficiency in 80% of patients. With GH replacement, catch-up growth and long-term benefit occurred. Disturbance of linear growth is an important feature of many patients with adrenal disorders in childhood. Assessment of its pathogenesis and careful management are necessary to ensure optimal final adult height. PMID- 11786681 TI - Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration. AB - Glucocorticoids have been widely used in the treatment of autoimmune and other diseases. Chronic steroid use, however, could cause proximal muscle weakness and atrophy, termed steroid myopathy. The onset of steroid myopathy is usually insidious and there are no specific laboratory findings except for elevated urinary creatine excretion. Muscle biopsy reveals non-specific type II fiber atrophy. There are many reports showing preventive effects of either growth hormone (GH) or insulin-like growth factor (IGF)-I on steroid myopathy. The pathogenesis of steroid myopathy is not fully understood. Recently, glutamine synthetase has been reported to play a key role in steroid myopathy. GH as well as IGF-I decreased the steroid-induced glutamine synthetase activity in skeletal muscle. PMID- 11786682 TI - Individualizing growth hormone dosing in children. AB - Much has been learned over the last three decades regarding the management of growth hormone (GH) treatment in children and adolescents. Current GH therapy enables most GH-treated children to attain a final height within the normal range and close to their target height. However, an optimal outcome is not always achieved and the approach to GH dosing differs among physicians and between countries. Furthermore, the individual response to GH varies dramatically between children, depending on age, the primary disease for which GH is prescribed and its severity, and other factors. Thus, the necessity to individualize treatment according to the specific needs of each child is being recognized. Consensus does not currently exist as to how to formulate individualized treatment plans. Nonetheless, a clear role for biochemical as well as auxological monitoring approaches has been established. Accurate determination of height velocity and interval height increase (expressed as the change in height z-score) continue to be the most important parameters in monitoring response to treatment. The importance of routinely monitoring serum insulin-like growth factor (IGF)-I and IGF binding protein-3 is an emerging paradigm. Roles have been firmly established for this approach in the assurance of compliance and safety (particularly to avoid long-term theoretical risks). IGF monitoring also has important potential utility as a tool to assess and optimize response to GH therapy through dose adjustment. In the years to come, we expect multiple optimization strategies including approaches such as prediction modeling as well as serum IGF monitoring and dose adjustment to evolve and improve. Currently, trials evaluating the utility of GH dose titration aiming to maintain the IGF-I level within a narrow range are being evaluated. The results of such large prospective randomized trials will surely help identify the value of individualizing GH dosing. PMID- 11786683 TI - From fixed to individual dosing in growth hormone-deficient adults. AB - Initial research studies of growth hormone (GH) replacement in adults employed what is now considered to be high doses of GH, from 12 to 25 microg/kg per day. While the beneficial effects of GH were demonstrated, there was a considerable incidence of side effects, most commonly edema and arthralgia. These side effects abated with a dose reduction. More recently, the Growth Hormone Research Society recommended initiating GH replacement at a dose of 0.3 mg/day irrespective of total or ideal body weight. The United States Food and Drug Administration approved pharmaceutical company package inserts that recommended beginning with a dose of 6 microg/kg per day with a maximum dose of 25 microg/kg per day and limiting the maximal dose to 12.5 microg/kg per day in adults over the age of 35 years. These should be considered as guidelines. PMID- 11786684 TI - Turner's syndrome: a paediatric perspective. AB - In childhood the symptoms with the greatest impact on girls with Turner's syndrome are: (1) congenital cardiac abnormalities (which can be corrected by surgical intervention); (2) short stature (mean adult height between 142 and 147 cm); and (3) ovarian failure (absent spontaneous puberty). Recent studies have shown that growth hormone (GH) treatment in young girls (8 years of age or younger) with Turner's syndrome results in normalization of adult height in most of the girls when using the 'standard' GH dose of about 4 IU/m(2) per day ( approximately 0.045 mg/kg per day). Higher GH doses (6 or 8 IU/m(2) per day) or the use of oxandrolone may be more effective, but their efficacy on adult height and safety in the very long term still have to be proven. If GH treatment is started early, low-dose oestrogens for induction of puberty can be given at 12 years of age without interfering with the capability of the GH treatment to normalize adult height. GH does not seem to have negative side effects on body proportions, cardiac dimensions, blood pressure, carbohydrate metabolism or bone mineral density. PMID- 11786685 TI - Medical problems of adult Turner's syndrome. AB - Several issues should be addressed when managing women with Turner's syndrome. Female sex hormone substitution should be offered to help prevent the increased morbidity seen in Turner's women, which consists of an increased risk of fractures and osteoporosis, and a clustering of diseases such as ischaemic heart disease, hypertension, stroke and type 2 diabetes, the latter entities being part of the insulin resistance syndrome. Furthermore, hypothyroidism is often seen, and the risk of type 1 diabetes may also be increased. Congenital malformations of the heart are frequently seen in Turner's syndrome, possibly increasing the risk of dissecting aorta aneurysm. Liver enzymes are often elevated and there may be an increased risk of liver cirrhosis. Mortality seems to be increased in Turner's syndrome, women with the "pure" 45,X karyotype being the most severely affected. In clinical practice, careful monitoring of glucose and bone metabolism, weight, thyroid function and blood pressure should be carried out. A cardiovascular risk profile should be determined and the patient informed of the risks and benefits of sex hormone replacement therapy. Sex hormone replacement therapy is highly recommended, although at present there are no longitudinal data documenting the long-term positive effect of sex steroid substitution. However, hypogonadism is expected to explain at least part of the decreased lifespan found in Turner's syndrome. Since general physicians only encounter these patients infrequently, it is recommended that the care and treatment of Turner's syndrome be centralized. PMID- 11786686 TI - Health-related quality of life: methods of assessment. AB - Developing a health-related quality of life (HRQOL) assessment requires both a conceptual model and an extended plan whereby the assessment can continue to be developed with repeated applications. While generic HRQOL assessments exist and can be readily applied, it is when the assessment is integrated into the treatment development process that it is of most value, and to do this optimally requires either disease or study-specific assessments. Investigators were encouraged to view the assessment task as an information processing activity, and to be as concerned about how a person generates an HRQOL assessment as much as what they state their HRQOL to be. The added value of doing an HRQOL assessment is also discussed. PMID- 11786687 TI - Impact of growth hormone (GH) therapy on quality of life along the lifespan of GH treated patients. AB - The relationship between growth hormone (GH) deficiency (GHD) and quality of life (QOL) is coming into sharper focus. Psychological studies of short GHD children referred for GH treatment sometimes show that they have a poor QOL, often due to their feelings of anxiety, depression, social isolation and difficulties maintaining attention. These difficulties may lead to low academic achievement and impoverished interpersonal skills, both of which impact on life satisfaction and productivity. Recent observations suggest that short children who are not referred for medical diagnosis do not experience the same problems. We have observed that after patients are started on GH therapy the incidence of behavioral problems declines to within normal limits on standardized psychometric tests. Pediatric GHD patients are not generally followed closely after growth targets are achieved. Over the past 25 years, several observers have noted that many patients treated with GH in childhood report poor QOL during young adulthood despite achievement of acceptable height and replacement of necessary hormones. They appear, as a group, to be underemployed, often unmarried, and sometimes unhappy. Some have suggested that this may be due to their overprotected early childhood. We have examined a cohort of young adults treated with GH during childhood and found they exhibit symptoms of previously undetected psychiatric disorder. Anxiety, depression, panic disorder and obsessive compulsive disorder were found. Strikingly, the incidence of a particularly disabling anxiety disorder, social phobia, was detected in 38% of one of our groups. This disorder occurs in approximately 13% of the general population. Similar QOL outcomes have been reported in adults who became GHD in later life. We conclude that the spectrum of potential disabilities tied to GHD is broader than previously thought. Management of these patients should include consideration of QOL issues throughout their lifespan. Potential treatment strategies may include continuation of GH therapy as indicated, psychotropic medication, or psychosocial support and rehabilitation. PMID- 11786688 TI - Computer-guided, population-based screening system for growth disorders (CrescNet) and on-line generation of normative data for growth and development. AB - The mean age at which the diagnosis of growth disorders such as Turner's syndrome, growth hormone (GH) deficiency or true GH-dependent gigantism is established is still rather late in many countries around the world. In addition, the question of secular trends in a given population and the rate at which childhood obesity is increasing in industrialized countries make it mandatory to establish a time-adapted system to develop percentiles for body height, weight and body mass index (BMI) and also to develop a screening system for growth disorders. In 1998 we established a network, now involving more than 160 paediatric practices in Germany and seven paediatric endocrinology departments. Paediatricians record heights, weights and growth velocities of all children in their care and systematically feed the data into the database at our centre usually by mailing formatted, structured data tickets. Data are then continuously analysed at the centre and the paediatricians in the network are informed immediately about their individual patients' growth situations via phone or E mail (feedback system). Regular annual conferences including structured reports, scientific presentations and discussion groups are organized for all participants at our centre. By May 2001, the data of 83,721 children and adolescents had been analysed. The mean values for height were 1-1.5 cm higher than the mean values in the German Synthetic Growth Curve, which serves as an internal standard. However, and most importantly, in comparison with the internal standard and historical normative data from Germany and Switzerland, there is a continuous increase in the 97th percentile for weight and BMI, while the third percentile remains unchanged. In addition, many children with short stature and tall stature due to a variety of endocrine disorders and genetic diseases which had not been diagnosed previously are now being identified. In conclusion, the databank allows for a continuous adaptation of normative curves based on a large number of children in a given population, i.e. eastern Germany. Secondly, the system allows for detection of pathological growth curves and is already serving to diagnose growth disorders in a defined population in a systematic way. PMID- 11786689 TI - Multiple endocrine neoplasia. AB - Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumours involving two or more endocrine glands; two major forms, referred to as MEN1 and MEN2, are recognized. MEN1 is characterized by parathyroid, pancreatic islet and anterior pituitary tumours, whilst MEN2 is characterized by medullary thyroid carcinoma (MTC) in association with phaeochromocytoma. There are three clinical variants, referred to as MEN2A, MEN2B and MTC-only. All these forms of MEN may be inherited as autosomal dominant syndromes. The MEN1 gene is on chromosome 11q13 and about 300 MEN1 mutations have been identified. These are of diverse types and are scattered throughout the coding region. There is also a lack of genotype phenotype correlation. All these findings make it difficult to implement MEN1 mutational analysis in the clinical setting. The situation in MEN2 is more straightforward. The gene causing all three MEN2 variants is located on chromosome 10cen-10q11.2, and is the c-ret proto-oncogene which encodes a tyrosine kinase receptor with cadherin-like and cysteine-rich extracellular domains, and a tyrosine kinase intracellular domain. Specific mutations of c-ret have been identified for each of the three MEN2 variants and mutational analysis has been used in the diagnosis and management of patients and families with the MEN2 variants. PMID- 11786690 TI - The growth hormone axis: why is pattern of hormone exposure so important? PMID- 11786691 TI - Thyroid hormone replacement therapy. AB - Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption phase, associated with palpitations. Liothyronine (T(3)) has the same drawback and requires twice-daily administration in view of its short half-life. Synthetic levothyroxine (L-T(4)) has many advantages: in view of its long half-life, once daily administration suffices, the occasional missing of a tablet causes no harm, and the extrathyroidal conversion of T(4) into T(3) (normally providing 80% of the daily T(3) production rate) remains fully operative, which may have some protective value during illness. Consequently, L-T(4) is nowadays preferred, and its long-term use is not associated with excess mortality. The mean T(4) dose required to normalize serum thyroid stimulating hormone (TSH) is 1.6 microg/kg per day, giving rise to serum free T(4) (fT(4)) concentrations that are slightly elevated or in the upper half of the normal reference range. The higher fT(4) values are probably due to the need to generate from T(4) the 20% of the daily T(3) production rate that otherwise is derived from the thyroid gland itself. The daily maintenance dose of T(4) varies widely between 75 and 250 microg. Assessment of the appropriate T(4) dose is by assay of TSH and fT(4), preferably in a blood sample taken before ingestion of the subsequent T(4) tablet. Dose adjustments can be necessary in pregnancy and when medications are used that are known to interfere with the absorption or metabolism of T(4). A new equilibrium is reached after approximately 6 weeks, implying that laboratory tests should not be done earlier. With a stable maintenance dose, an annual check-up usually suffices. Accumulated experience with L-T(4) replacement has identified some areas of concern. First, the bioequivalence sometimes differs among generics and brand names. Second, many patients on T(4) replacement have a subnormal TSH. TSH values of < or =0.1 mU/l carry a risk of development of atrial fibrillation and are associated with bone loss although not with a higher fracture rate. It is thus advisable not to allow TSH to fall below--arbitrarily--0.2 mU/l. Third, recent animal experiments indicate that only the combination of T(4) and T(3) replacement, and not T(4) alone, ensures euthyroidism in all tissues of thyroidectomized rats. It is indeed the experience of many physicians that there exists a small subset of hypothyroid patients who, despite biochemical euthyroidism, continue to complain of tiredness, lack of energy, discrete cognitive disorders and mood disturbances. As organs vary in the extent to which their T(3) content is derived from serum T(3) or locally produced T(3) from T(4), these complaints may have a biologic substrate; for example, brain T(3) content is largely determined by local deiodinase type II activity. Against this background it is of interest that a number of psychometric scores improved significantly in hypothyroid patients upon substitution of 50 microg of their T(4) replacement dose by 12.5 microg T(3). Confirmatory studies on this issue are urgently awaited. It could well be that a slow-release preparation containing both T(4) and T(3) might improve the quality of life, compared with T(4) replacement alone, in some hypothyroid patients. PMID- 11786692 TI - Physiological principles of endocrine replacement: estrogen. AB - The major biologically active circulating estrogen in both males and females is estradiol (E(2)). Circulating E(2) is a product of the ovarian granulosa cell and the testicular Leydig cell. Its gonadal formation is dependent on A-ring aromatization of its immediate precursor, testosterone, by a particular isoform of the enzyme aromatase, which also catalyses the conversion of the much weaker androgen, androstenedione, to the weak estrogen, estrone. E(2) is also formed in non-gonadal tissues, such as adipose tissue, liver, muscle and brain. Only adipose tissue makes significant extra-gonadal contributions to circulating estrogen. Loss of ovarian function during reproductive life, as a result of loss of gonadotropin secretion (secondary hypogonadism) or as a result of premature ovarian failure (generally defined as cessation of ovarian function prior to age 40), results in loss of the majority of circulating E(2) and of luteal progesterone. Loss of ovarian function at the menopause likewise results in a 90% loss of circulating E(2). The consequences of loss of ovarian function during reproductive life may be severe. Symptoms include hot flushes, night sweats, vaginal dryness and dyspareunia, loss of libido, loss of bone mass with subsequent osteoporosis and abnormalities of cardiovascular function, including a substantial increase in the risk of ischemic heart disease. Various regimens of estrogen replacement have been employed, aiming to eliminate symptoms, restore well-being and avert the consequences of estrogen depletion. The commonly adopted form of replacement is with the low-dose oral contraceptive pill for reasons of convenience, cost, efficacy, general freedom from side effects and the psychological advantage that many of the patient's peer group are also "taking the pill". An often neglected aspect of hormone therapy in the reproductive age group is the therapeutic use of testosterone. The application of such principles to the postmenopausal period is more problematic, as there is a common perception that the menopause is a normal physiological occurrence and that it is therefore not physiological to offer hormone therapy at that time. The pragmatic approach is to recommend standard therapy with estrogen and progestogen for the management of menopausal symptoms and to recommend longer term hormone replacement in the light of the individual's needs and current data with regard to efficacy for protection from osteoporosis and cardiovascular disease. PMID- 11786693 TI - Testosterone deficiency and replacement. AB - In the human male, testosterone is the major circulating androgen. More than 95% of circulating testosterone is secreted by the testis with a production rate of 6 7 mg/day. The clinical effects of androgens are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. Overt hypogonadism results in reductions in bone mineral density, alterations in body composition and effects on mood, aggressive behaviour, cognitive function, sexual function and several factors important for cardiovascular risk. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat, and positive effects on quality of life following treatment. The benefits of therapy in men with milder degrees of hypogonadism, and elderly men with "physiological" testosterone deficiency, are less clear-cut, and the appropriate biochemical cut off below which replacement should be offered has not been clearly defined. Several options are available for androgen replacement in adult men. Oral testosterone, intramuscular injections, subcutaneous implants and transdermal therapy have all been used. Each mode of delivery has advantages and drawbacks and the choice between them will often depend on patient reference. Recent advances include the development of longer-acting intramuscular preparations, which offer more stable androgen levels with fairly infrequent injections, and testosterone gel which appears to provide transdermal replacement without a high incidence of skin reactions. This article will examine the evidence concerning the impact of male hypogonadism and the response to androgen therapy. The question of who to treat will be addressed with particular reference to mild hypogonadism and hypogonadism in the elderly. Finally, an overview of the different modes of replacement therapy will be presented. PMID- 11786694 TI - Purification and distribution of ghrelin: the natural endogenous ligand for the growth hormone secretagogue receptor. AB - Growth hormone secretagogues (GHS) are small synthetic molecules that act through a specific G-protein coupled receptor (GPCR) termed GHS-R, which is a distinct receptor from that of growth hormone releasing hormone (GHRH). This receptor was one of the orphan GPCR, i.e. a GPCR with no known natural ligand, until we purified its endogenous ligand from rat stomach and named it "ghrelin". Ghrelin is a 28-amino-acid peptide, in which the serine 3 is modified by an n-octanoic acid and this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin from the stomach and hypothalamus. PMID- 11786695 TI - The future of endocrinology and the endocrinologist of the future. PMID- 11786696 TI - A model of intracranial pulsations. PMID- 11786697 TI - Early treatment of posthemorrhagic hydrocephalus in low-birth-weight infants with valveless ventriculoperitoneal shunts. AB - The surgical treatment of posthemorrhagic hydrocephalus (PHH) in low-birth-weight infants (LBWI) is debated. In a few cases, hydrocephalus progresses rapidly and requires early drainage, but valves and ventriculostomy have a high rate of complications in the early phase. Temporary valveless shunt (VLS) is proposed as an alternative treatment of acute PHH in LBWI. Thirteen infants with PHH, weighing less than 2,000 g at birth, were treated with VLS, which was systematically converted into a valve-regulated shunt (VRS) after a few weeks; during the same period, 27 others were treated with VRS initially. The use of VLS presented significantly more shunt obstructions, but not more shunt infections, than VRS. Although placement of VLS was performed earlier, and in smaller babies than VRS, the outcome after a mean 9.1-year follow-up period was comparable in both groups, and only shunt infection was correlated with a poor outcome. We conclude that VLS is a valuable treatment of rapidly evolving PHH in LBWI. PMID- 11786698 TI - The application of controlled intracranial hypertension in slit ventricle syndrome patients with obstructive hydrocephalus and shunt malfunction. AB - When a shunted patient with slit-ventricle syndrome (SVS) presents with a shunt malfunction or infection, the third ventricle may not be of sufficient caliber, despite the shunt malfunction, to allow atraumatic passage of an endoscope to the floor of the third ventricle. We describe four slit ventricle syndrome patients with respectively 24, 12, 18 and 2 prior shunt revisions who presented with shunt infection. In each patient the shunt was externalized and controlled intracranial hypertension (CIH) was applied over an average of 5.8 days by raising the height of the external ventricular drain (EVD) bag to a mean height of 18.8 cm above EAM. This increased the mean transverse third ventricular diameter from an average of 0.28 cm on admission to 1.13 cm after application of CIH. Endoscopic third ventriculocisternostomy (ETV) was satisfactorily performed in three of the four patients who remain shunt free after a mean follow-up of 21.3 months. CIH followed by ETV is an option in selected SVS patients who present with shunt malfunction or infection. PMID- 11786699 TI - Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. AB - OBJECTIVE: To evaluate the prognostic factors influencing the length of survival of pediatric patients with cerebellar astrocytomas. METHODS: The clinical data of 102 patients under the age of 12 years with cerebellar astrocytomas were retrospectively analyzed. The radiological features, surgical findings, histology and adjuvant radiotherapy were reviewed. Patients were followed up on an outpatient basis. Computerized tomography (CT) scans of the brain were performed to detect recurrence. RESULTS: The age of the patients at presentation varied from 10 months to 12 years. The mean age at presentation was 7 years and 11 months. The average duration of symptoms was 5.8 months. The clinical features were predominantly related to intracranial hypertension and the location of the tumor. Twenty-six tumors were located in the vermis and 76 in the cerebellar hemisphere. The brain stem was involved in 20 patients. All 102 patients had a preoperative contrast-enhanced CT scan. Midline vermian tumors were predominantly solid and enhancing, whilst the hemispheric tumors were cystic and nonenhancing. The tumors were graded into three subgroups based on histological characteristics: pilocytic astrocytoma, low-grade fibrillary astrocytoma and high grade fibrillary astrocytoma. Total, radical and subtotal excision, as determined by the surgical impression, were performed in 82, 16 and 4 patients, respectively. Postoperative radiotherapy was administered to 12 patients. CSF diversion was carried out in 11 of 79 cases who had moderate to severe hydrocephalus. CONCLUSIONS: Our study has shown that the location of the tumor (p < 0.05), histological grade (p < 0.001) and the extent of tumor resection (p < 0.001) have a significant and definitive relationship to the length of survival of pediatric patients with cerebellar astrocytomas. The patient's age (p > 0.05) does not influence the outcome. We could not evaluate the effect of brain stem involvement and adjuvant radiotherapy in our study because of the small sample size. PMID- 11786700 TI - Spinal sagittal malalignment following surgery for primary intramedullary tumours in children. AB - BACKGROUND/OBJECTIVE: As prior studies analysed predictive factors for various post-laminectomy spinal deformities in mixed spinal regions, age groups or pathologies, their validity and conclusions were unclear. The objective of this study was to determine predictive factors for worsened cervical or thoracic spinal sagittal alignment following laminectomy or laminotomy for primary intramedullary spinal cord tumours in children. METHODS: In this retrospective study, patients treated between 1980 and 1998 were reviewed. Changes in spinal alignment at the last follow-up compared to the pre-operative state were studied. Factors analysed were age, pre-operative spinal alignment, procedure types (laminectomy or laminoplasty), number of laminae operated, surgery of C2 or T1 laminae, histological grade, presence of post-operative neurological deficit and post-operative radiotherapy. RESULTS: There were 27 patients. The mean age was 5.6 years (range 1.3-14.0 years), and the mean duration of follow-up was 3.7 years (range 0.075-9.9 years). In the cervical-cervicothoracic surgical group (n = 12), alignment worsened post-operatively in 3 patients. The number of laminae operated upon had a statistically significant impact on the development of post operative kyphosis (p = 0.07). In the thoracic-thoracolumbar surgical group (n = 15), alignment worsened in 9 patients. Procedure types were statistically significantly different, with laminectomy associated with an increased risk of post-operative kyphosis (p = 0.01). All 5 patients who had spinal fusion for worsened post-operative alignment were in the thoracic-thoracolumbar group; no patients in the cervical-cervicothoracic group required spinal fusion (p = 0.047). Other predictive factors did not reach statistical significance (p > 0.05). CONCLUSIONS: Worsened spinal sagittal alignment following laminectomy or laminoplasty and the need for spinal fusion is more common in the thoracic thoracolumbar region than in the cervical-cervicothoracic region. In the cervical cervicothoracic region, operation on a greater number of laminae tends to increase the risk of worsened alignment. In the thoracic-thoracolumbar region, laminectomy is associated with worsened alignment, while laminoplasty reduces this risk; also, pre-operative kyphotic deformity tends to increase the risk of worsened alignment post-operatively. PMID- 11786701 TI - Pituitary adenoma associated with gigantism and hyperprolactinemia. AB - An 11-year-old girl presented with excessive growth, headache, left visual loss and seizures. Her growth hormone (GH) and prolactin (PRL) levels were high and magnetic resonance imaging findings showed an invasive macroadenoma. Gross total tumor removal was performed and then radiotherapy and medical therapy were given. During the follow-up, she developed ACTH deficiency, secondary hypothyroidism and hypogonadism requiring replacement therapy. It is still unclear whether the biological characteristics of GH- and PRL-secreting tumors are different in children from those in adults. More data are needed before a definitive conclusion can be established. PMID- 11786702 TI - Early management of craniocerebral injury with avoidance of post-traumatic leptomeningeal cyst formation. Report of two cases. AB - Leptomeningeal cyst, or growing skull fracture, is a rare complication of pediatric head trauma. This entity is typically diagnosed several weeks or months following head trauma when an enlarging scalp mass is recognized. Progressive neurologic deficits (seizures, paresis) can accompany this process, which typically do not improve following conventional surgical treatment. Given that radiographic findings are highly predictive of which children are likely to develop a leptomeningeal cyst, we have adopted a policy of early management in an effort to avoid difficult surgical dissections and progressive neurologic sequelae seen with delayed intervention. The cases of two infants with skull fractures are used to illustrate our approach toward early management of post traumatic leptomeningeal cysts. PMID- 11786704 TI - Acute subdural haematomas following ventouse-assisted delivery. PMID- 11786703 TI - Pneumocephalus in a newborn with an open myelomeningocele. PMID- 11786705 TI - Giant cavernous angioma. PMID- 11786706 TI - Spontaneous spinal epidural abscess. PMID- 11786707 TI - 21st century perspective on chronic obstructive pulmonary disease. AB - The prediction that chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2020 has enormous economic repercussions. Yet many issues and questions remain unresolved. For example, how can population studies of morbidity and mortality be viewed as comparable, without a worldwide consensus on the definition of COPD? How can the early diagnosis of COPD be improved? Why is it that only a minority of smokers develop COPD, despite tobacco smoking being the primary risk factor for chronic bronchitis and emphysema? How can the efficacy of smoking cessation interventions be improved? To what extent are the pathologic changes in the lungs reversible - and, if so, at what stage? And to what degree is it appropriate to emphasize the similar features of COPD and asthma? It is to be hoped that the emerging post genomic and proteomic climate will facilitate the unlocking of the genetic substrate for COPD, and thus promote greater therapeutic specificity and efficacy. PMID- 11786708 TI - Is pulmonary hypertension common in uncomplicated OSA? PMID- 11786709 TI - Bronchoscopy in daily practice: back to basics. PMID- 11786710 TI - Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics. AB - BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension. PMID- 11786711 TI - Physiologic evaluation of 4 weeks of nocturnal nasal positive pressure ventilation in stable hypercapnic patients with chronic obstructive pulmonary disease. AB - BACKGROUND: The long-term daily use of noninvasive mechanical ventilation (NIMV) to treat chronic respiratory failure in chronic obstructive pulmonary disease (COPD) patients is not widely recommended, partly because of a lack of clear clinical results and partly because the physiological mechanisms by which the daily application of NIMV would be helpful in these patients have not yet been clarified. OBJECTIVES: We designed a physiological study in order to assess the effects of supervised long-term NIMV on gas exchange, respiratory muscle function, pulmonary mechanics and to ascertain the possible effect of the treatment in responders and nonresponders. METHODS: Fourteen consecutive inpatients with stable hypercapnic COPD (pH = 7.37 +/- 0.01; PaCO(2) = 56.73 +/- 6.48 mm Hg) underwent 4 weeks of nocturnal NIMV delivered with a bilevel ventilator 'physiologically' set to reduce tidal transdiaphragmatic pressure (Pdi) by at least 50% and the amount of dynamic intrinsic positive end-expiratory pressure by 70%. Various measurements were compared with those obtained in a control group of consecutive patients with comparable baseline characteristics who refused NIMV and underwent breathing exercises for the same period of time. RESULTS: By the end of the 4 weeks NIMV had induced a slight but significant (p < 0.01) reduction in resting PaCO(2) (53.78 +/- 5.64 mm Hg) associated with a decrease in the pressure time product of the diaphragm per minute (from 172 +/- 60 to 136 +/- 61 cm H(2)O/l/s; p < 0.05). This latter value was primarily due to a significant shortening of the inspiratory duty cycle, while Pdi and lung mechanics were not modified. Eight of the 13 NIMV-treated patients (1 dropped out for nonmedical reasons) had a clear reduction in PaCO(2) (>3 mm Hg or >5% from enrollment) and were classified as responders. The acute reduction in PaCO(2) during the first trial with NIMV resulted to be a strong index of the final response. The subgroup of responders had a significantly increased maximal Pdi (from 41 +/- 19 to 49 +/- 23 cm H(2)O, p < 0.05) and an enhanced ability of the ventilatory pump to clear CO(2) (9.7 +/- 3.4 vs. 7.2 +/- 2.9 cm H(2)O x s/min; p < 0.01). No significant changes were observed in the control group. CONCLUSIONS: These results suggest that in a remarkable and identifyable proportion of patients with stable hypercapnic COPD, nocturnal NIMV may decrease resting PaCO(2), reraising the role of chronically supporting the respiratory pump. PMID- 11786712 TI - Effect of oxygen on sleep and breathing in patients with interstitial lung disease at moderate altitude. AB - OBJECTIVE: To investigate the impact of oxygen on sleep and breathing in patients with interstitial lung disease (ILD) in Mexico City, at 2,240 m of altitude. PARTICIPANTS: Nineteen ILD patients with a mean FVC of 58 +/- 17% pred. (SD) and a mean PaO(2) of 51 +/- 6 mm Hg were recruited from a pulmonary clinic in a tertiary referral center. In addition, 14 normal control subjects, matched for age and gender, were studied. All patients underwent two consecutive full polysomnographies (PSG), one breathing room air and one breathing supplementary oxygen through nasal prongs, in random order. Controls were studied for one night breathing room air. RESULTS: The mean oxygen saturation (SaO(2)) in ILD patients was 82.3 +/- 9.1% during sleep on air and 94.8 +/- 2.9% on oxygen (p < 0.001). In controls it was 92.9 +/- 1.9% (p < 0.001). Sleep efficiency was similar in patients and controls (75 vs. 82%, p > 0.05) and did not change with oxygen (77%). Arousal index was 12.4 +/- 6.9.h(-1) in ILD patients breathing room air and 12.9 +/- 9.1.h(-1) breathing oxygen while in controls it was 11.4 +/- 5.4.h( 1). Breathing frequency (f) during sleep was 24.7 +/- 4.2 in ILD patients and decreased breathing oxygen to 22.5 +/- 3.6 (p < 0.001) but was still higher than in controls (15.6 +/- 2.7; p < 0.001). Similarly, the heart rate (HR) in ILD and controls was 79 +/- 12 and 68 +/- 8, respectively (p < 0.001), and decreased to 68 +/- 4 when patients breathed oxygen (p < 0.001). CONCLUSIONS: Oxygen substantially decreases HR and f, but does not normalize the f in ILD patients. The impact of hypoxia on sleep efficiency and arousal index was not demonstrable in our patients acclimatized to moderate altitude. PMID- 11786713 TI - Natural killer cell activity in multidrug-resistant pulmonary tuberculosis. AB - BACKGROUND: Multidrug-resistant pulmonary tuberculosis (MDRTB), a major problem in developing countries, may result from either insufficiency of host cellular immune response or mycobacterial mechanisms which has been more intensively investigated so far. OBJECTIVES: The aim of the study was to investigate natural killer cell activity (NKA) and T lymphocyte subsets in HIV- patients with secondary MDRTB. METHODS: 20 male patients with MDRTB (mean age 38 +/- 8 years), 15 nonresistant tuberculosis male patients (NRTB) (mean age 36 +/- 11 years) and 12 healthy male controls (mean age 35 +/- 8 years) were included. The percentages of CD3+, CD4+, CD8+, CD25+, CD11b+ and CD16+56+ cells were measured by flow cytometric analysis of peripheral blood lymphocytes (PBL). NKA was evaluated using the anticandidal index method. RESULTS: The mean tuberculin response was higher in MDRTB and NRTB patients compared to controls (15.4 +/- 3.8, 15.1 +/- 3.3 and 10.9 +/- 2.8 mm, respectively; p < 0.001). There was no significant correlation between PPD response and PBL subsets or NKA. The percentages of both CD3+ and CD3+CD4+ T lymphocytes were significantly lower in MDRTB (62.4 +/- 12.1 and 33.9 +/- 9.0%) compared to NRTB (70.8 +/- 7.5 and 42.9 +/- 8.6%; p < 0.05). Patients with MDRTB had significantly lower NKA compared to NRTB and controls (30.9 +/- 11.3, 49.7 +/- 15.5 and 40.0 +/- 8.5%, respectively; p < 0.01). CONCLUSION: This reduction in NKA may suggest a role for impaired NK function in the pathogenesis of MDRTB in HIV- patients. PMID- 11786714 TI - Pulmonary tuberculosis in patients with diabetes mellitus. AB - BACKGROUND: Diabetes mellitus has been reported to modify the presenting features of pulmonary tuberculosis, but there are varying data, particularly regarding the association with lower lung field involvement. OBJECTIVES: To determine whether diabetes mellitus alters the clinical and radiographic manifestations of tuberculosis in nonimmunocompromised hosts and to define the determinants of lower lung field involvement. METHODS: A retrospective review of the records of all patients with tuberculosis and diabetes mellitus seen during a 14-year period and of an age- and sex-matched nondiabetic control group with tuberculosis was carried out. The duration of symptoms, tuberculin reaction, bacteriologic and radiographic findings of the two groups were compared. RESULTS: The presence of diabetes mellitus was found not to have an effect on patients' symptomatology, bacteriology results, tuberculin reaction and localization of pulmonary infiltrates. On the other hand, fewer diabetic patients were smear-positive and fewer had reticulonodular opacities compared with the control patients. A higher number of insulin-dependent diabetic patients presented with cavitary disease as compared with nondiabetic controls. Lower lung field tuberculosis was significantly associated with female gender and, in patients older than 40 years, was more frequently observed in diabetics. CONCLUSION: These data show that diabetes does not affect the presenting features of pulmonary tuberculosis to a large extent and is only associated with lower lung field disease in older patients. PMID- 11786715 TI - Factors influencing improvement and remission rates after thymectomy for myasthenia gravis. AB - BACKGROUND: Thymectomy has become an accepted option in the treatment of myasthenia gravis (MG). However, the optimal selection of patients for surgery remains controversial. OBJECTIVE: The objective of the study is to define factors influencing improvement and remission rates after thymectomy for MG. METHODS: We retrospectively reviewed our experience in the surgical management of patients with MG over the last 20 years, and analyzed if patient's age, sex, preoperative Osserman Stage, thymic histology, duration of symptoms, or radiological findings influenced outcome. RESULTS: There were 25 women and 10 men. Most of them presented with Osserman stage IIA (n = 12) and stage IIB (n = 17). Hyperplasia of the thymus was observed in 15 patients (43%), thymoma in 12 (34%), and atrophic or normal thymus in 8 (23%). Computed tomography (CT) had a positive predictive value of 91% in detecting thymoma and of 80% in detecting thymic hyperplasia. Over a mean follow-up of 96 months, MG improved markedly in 26 patients. Postoperative improvement was significantly greater in patients with advanced MG (stage IIB, III and IV), whereas a higher rate of remission occurred in patients with mild MG (stage I and IIA), and in those with thymic hyperplasia. No relation was observed between outcome and age, sex, duration of symptoms and abnormal CT findings. CONCLUSIONS: The beneficial effects of thymectomy are characterized by postoperative clinical improvement in most patients with moderate to severe preoperative myasthenic involvement and by a higher remission rate in patients with thymic hyperplasia and/or mild myasthenic symptoms. PMID- 11786716 TI - Clinical course and management of patients undergoing open window thoracostomy for thoracic empyema. AB - BACKGROUND: While open window thoracostomy (OWT) is a safe procedure and is indicated in patients who have thoracic empyema either with or without a bronchopleural fistula, it may prolong the hospital stay. OBJECTIVES: We retrospectively analyzed the relationship between the etiology of thoracic empyema and the open window interval (OWI). METHODS: Between January 1986 and May 1997, 53 patients resistant to conventional therapy underwent OWT for thoracic empyema at the Department of Surgery of the National Minami-Fukuoka Chest Hospital. The patients were classified into five groups based on the etiological findings of thoracic empyema. 44 patients also underwent closure of the window until June 1999. RESULTS: The average OWI was 180.4 +/- 51.9 (mean +/- SE) days for postoperative empyemas in lung cancer, 128.0 +/- 32.1 days for bacterial nontuberculous empyemas, 189.6 +/- 24.1 days for fungal empyemas, 365.8 +/- 201 days for empyemas caused by atypical mycobacteria and 322.0 +/- 58.7 days for tuberculous empyemas. There was no evidence that the OWI was related to either sex, age, etiology of thoracic empyemas, performance status, the existence of bronchopleural fistulae, complications of diabetes mellitus or preoperative malnutrition status in multivariable models. 5 patients underwent a second OWT because of recurrence of empyema. Mortality rate was 7.5%. CONCLUSIONS: There was no relationship between clinical factors including nutritional assessment and OWI. OWT generally is a safe and effective procedure for thoracic empyema resisting to conventional therapy except that it can make an extended hospital stay necessary. PMID- 11786717 TI - Usefulness of various diagnostic techniques during fiberoptic bronchoscopy for endoscopically visible lung cancer: should cytologic examinations be performed routinely? AB - BACKGROUND: The question of which combination of procedures gives the best diagnostic yield following fiberoptic bronchoscopy is controversial. OBJECTIVES: To evaluate the value of various diagnostic techniques following fiberoptic bronchoscopy in the diagnosis of endoscopically visible lung cancer. METHODS: The study included 98 patients found to have endobronchially visible tumor during routine daily bronchoscopy. Endobronchial lesions were classified as mass, submucosal lesion and infiltration. Washings, brushings and forceps biopsies were obtained in all subjects. Transbronchial needle aspirations were performed in 67 of 76 cases with mass or submucosal lesions. RESULTS: Bronchoscopy was diagnostic for cancer in 88 (89.8%) of the 98 patients. Forceps biopsy specimens gave positive result in 82.7% of cases, transbronchial needle aspirates in 68.6%, brushings in 68.4%, and washings in 31.6%. Combination of forceps biopsy and brushing cytology yielded a positive result for lung cancer in 87 patients. The addition of brushings increased the diagnostic yield of bronchoscopy from 82.7% to 88.8% (p < 0.05). Collection of washing specimens in addition to forceps biopsy did not increase the yield of forceps biopsy. Transbronchial needle aspiration gave an additional yield of 1%. CONCLUSIONS: Routine cytological examination of bronchial washings does not increase the yield of forceps biopsy specimens. Transbronchial needle aspiration may give an additional positive yield to forceps biopsy. We conclude that a combination of forceps biopsy and brushing is the best strategy in the diagnosis of bronchoscopically visible lung cancer. PMID- 11786718 TI - The effect of erythromycin on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum. AB - BACKGROUND: Erythromycin has been shown to diminish sputum production in hypersecretory states by a mechanism that is still unclear. OBJECTIVES AND METHODS: We have investigated the effect of erythromycin on the ciliary transportability of cystic fibrosis and non-cystic fibrosis bronchiectasis sputum in vitro using the mucus-depleted bovine trachea. RESULTS: Additional erythromycin in concentrations up to 20 microg/g did not significantly alter the ciliary transportability of sputum from 6 cystic fibrosis and 6 bronchiectasis patients. Sputum viscoelasticity measured with parallel-plate rheology was also little changed. These erythromycin concentrations also had little effect on the beating frequency of bovine tracheal cilia. CONCLUSIONS: These results suggest that the presence of erythromycin in sputum neither alters the physical properties of the gel nor the activity of cilia. The clinical effects of erythromycin on pulmonary hypersecretory states therefore have another explanation. PMID- 11786719 TI - A rare cause of Horner's syndrome: subclavian artery aneurysm. PMID- 11786720 TI - Persistent spontaneous pneumothorax in an adolescent with Marfan's syndrome and pulmonary bullous dysplasia. AB - A 16-year-old boy with Marfan's syndrome was admitted with progressive dyspnea due to a large spontaneous pneumothorax. Bullous pulmonary dysplasia was confirmed and pleural tube drainage did not affect the air leak. Complete recovery required surgical resection of the bulla responsible for the ongoing air leak. This case report highlights the issue of management for severe spontaneous pneumothorax in general, showing that the choice of treatment should not depend on the presence of pulmonary bullous dysplasia but on the clinical evaluation of the individual patient. PMID- 11786721 TI - Concurrent left-sided spontaneous pneumothorax in Japanese monogerminal twins. AB - Monogerminal twin brothers aged 17 were admitted because of concurrent left-sided spontaneous pneumothorax. A familial background of this common disease in association with the human leukocyte antigen (HLA) has been suggested; however, the actual mode of inheritance in association with HLA typing is still uncertain. HLA analysis in this family revealed the HLA-A24, B61 (40), Cw3, DR4, DR53, and DQ3 haplotype in the twins and their father, who also had a medical history of spontaneous pneumothorax. We report these cases as an extremely rare example of familial occurrence of spontaneous pneumothorax. PMID- 11786722 TI - Takayasu's arteritis presenting with bilateral parenchymal consolidations and severe respiratory failure. AB - This is a report of an unusual case of Takayasu's arteritis presenting with bilateral parenchymal infiltrations and severe respiratory failure caused by pulmonary hemorrhage. The patient was initially diagnosed and treated as protracted pneumonia. After the diagnosis of Takayasu's arteritis, she was successfully treated with high-fractioned oxygen and corticosteroid therapy. PMID- 11786723 TI - Bronchiolitis obliterans organizing pneumonia associated with Evans syndrome. AB - The association of bronchiolitis obliterans organizing pneumonia (BOOP) with insulin-dependent diabetes mellitus (IDDM) and Evans syndrome (autoimmune pancytopenia) has not been reported previously. We describe the case of a 4-year old child diagnosed with IDDM and Evans syndrome who presented malaise, fever and nonproductive cough for several months. The chest radiograph revealed several patchy alveolar opacities with peripheral and bilateral distribution and multiple hilar and mediastinal adenopathies. An open lung biopsy established the diagnosis of BOOP. During the follow-up over the next 7 years, the patient had chronic relapses in spite of corticosteroid treatment and developed restrictive lung disease. PMID- 11786724 TI - An unusual cause of nearly fatal hemoptysis. PMID- 11786725 TI - Monitoring asthma severity and response to treatment. AB - Guidelines for the management of asthma rely on various methods of assessing severity and how it changes in order to select the appropriate treatment. These methods have been developed from the basic clinical skills of history taking and physical examination to which attempts at improving objectivity have been added, such as the use of asthma diaries, the home recording of peak expiratory flow (PEF) or measurements of bronchial reactivity. The present review was an attempt to determine to what extent monitoring asthma by various techniques is justified. Unfortunately, diaries and home recording of PEF are easily faked and generally unreliable while objective tests, such as the measurement of bronchial reactivity or studies of induced sputum cannot be undertaken often enough for monitoring, and there is certainly the need for prospective longitudinal controlled studies. PMID- 11786726 TI - A 21-year-old patient with acute myeloid leukemia and bilateral pulmonary infiltrates. PMID- 11786727 TI - Vitamin K deficiency in diffuse alveolar hemorrhage associated with systemic lupus erythematosus. PMID- 11786728 TI - CA 125: the end of the beginning. AB - CA 125, a high-molecular-weight mucin, was first defined in 1981 by the monoclonal antibody OC125. Until recently, it has defied many attempts to purify it from a variety of sources, although many research groups have successfully raised antibodies that bind to CA 125. Nevertheless, CA 125 has demonstrated its considerable value as a marker in monitoring patients with ovarian cancer. This year, two research groups have succeeded in cloning the high-molecular-weight mucin CA 125. Their findings are summarized and the significance discussed in light of existing data from the human genome. PMID- 11786729 TI - The CA 125 gene: an extracellular superstructure dominated by repeat sequences. AB - CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated extracellular structure. This structure is dominated by a repeat domain composed of 156 amino acid repeat units which encompass the epitope binding sites. The molecule also includes an amino terminal domain of serine/threonine-rich sequences which would account for most of the O glycosylation known to be present in CA 125. CA 125 is an unusually large transmembrane glycoprotein. Its release from the surface of the cell is most probably dependent on cytoplasmic phosphorylation followed by proteolytic cleavage. The extracellular domain is characterized by a large number of repeat units (probably 60+) which encompass an interactive disulfide bridged cysteine loop and the site of OC125 and M11 binding. Sequencing the gene provides us with the ability to initiate the quest to understand the biological function of CA 125. PMID- 11786730 TI - Independent factors predict supranormal CA 15-3 serum levels in advanced breast cancer patients at first disease relapse. AB - Data currently available are insufficient to demonstrate a real utility for CA 15 3 in the diagnosis, staging or surveillance of breast cancer patients following primary treatment. The aim of this study was to determine if there was a correlation between supranormal CA 15-3 serum levels and clinical and biological variables in breast cancer patients at first disease relapse. From October 1988 to March 1998, 430 consecutive patients entered the study. Overall CA 15-3 sensitivity was 60.7%. Elevated CA 15-3 levels were found more frequently in patients with liver metastases (74.6%) and in those with pleural effusion (75.7%). CA 15-3 sensitivity was 70.4% in patients with estrogen-receptor positive (ER+) primary tumors and 45.9% in those with estrogen-receptor-negative (ER-) tumors (p < 0.0001). In patients with a limited extent of disease, marker sensitivity was 57.7% in ER+ tumors and 25.7% in ER- tumors (p < 0.0001). Logistic regression analysis showed ER status, disease extent and pleural effusion as independent variables associated with CA 15-3 positivity. The multivariate Cox analysis showed ER and disease extent as independent variables predicting overall survival, whereas CA 15-3 failed to be statistically significant. CA 15-3 was an independent variable only when the disease extent variable was removed. This study suggests that CA 15-3 in advanced breast cancer patients is a marker of both disease extent and ER status. The direct relationship with ER status indicates that CA 15-3 diagnostic sensitivity in the early detection of disease recurrence could be greater in ER+ patients than in ER ones. Furthermore, this suggests that patients with elevated CA 15-3 levels could have disease that is more sensitive to hormone manipulation than those with normal CA 15-3 values. PMID- 11786731 TI - Telomerase activity and expression of telomerase RNA component and catalytic subunits in precancerous and cancerous colorectal lesions. AB - To investigate the role of telomerase activity in colorectal adenoma-carcinomas, telomerase activity, human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were quantitatively analyzed in human cancerous and precancerous colorectal tissues. Sixty-six colorectal tumor specimens, including 10 invasive carcinomas, 6 mucosal carcinomas and 50 adenomas were evaluated. Ten specimens of normal tissue were also included in the study. Telomerase activity was assayed by semiquantitative fluorescence using the TRAP eze(TM) telomerase detection kit. Analysis of the expression of each telomerase subunit gene was performed by real-time PCR amplification. There was a positive correlation between histological atypia and telomerase activity (rho = 0.700, p < 0.0001), hTERT mRNA expression (rho = 0.603, p < 0.0001), and hTERC expression (rho = 0.290, p < 0.05). There was also a positive correlation between the levels of hTERT mRNA and telomerase activity (r = 0.455, p < 0.01). Significant differences in the levels of hTERT mRNA were shown between normal tissues and the adenomas (p < 0.05) and between the mucosal carcinomas and invasive carcinomas (p < 0.05). The values of hTERC expression in neoplastic tissues were significantly higher than in the normal tissues; however, there were no significant differences between the adenomas and the carcinomas. In summary, although upregulation of hTERC expression is an early event in adenoma development, hTERT mRNA expression is gradually upregulated during the adenoma-carcinoma sequence and may be a rate limiting determinant of telomerase activity. PMID- 11786732 TI - Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosa. AB - Proteolytic enzymes, such as type IV collagenases (MMP-2 gelatinase A, 72-kD type IV collagenase and MMP-9 gelatinase B, 92-kD type IV collagenase) play an important role in tumor invasion and metastasis. In the present study the levels of MMP-2 antigenic concentration and immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigenic concentrations were found to be statistically significantly higher in cancer tissue (mean 11.29 ng/mg protein) than in corresponding normal mucosa (10.23 ng/mg protein) (p = 0.008). There was also a positive correlation between MMP-2 antigenic concentration and clinicopathologic parameters such as grade (p < 0.001) and Dukes' stage (p = 0.001), but not with lymph node involvement. Immunohistological localization of MMP-2 was observed in tumor as well as in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade (p < 0.001), Dukes' stage (p < 0.001) and lymph node involvement (p < 0.001). PMID- 11786733 TI - Expression of oncofetal fibronectin and syndecan-1 mRNA in 18 human lung cancer cell lines. AB - It has been suggested that fibronectin (FN) and syndecan play an important role in many aspects of cell-substrate interactions including cell adhesion. We hypothesized that oncofetal FN (onfFN) and syndecan play an important role in the process of adhesion of several human lung cancer cell lines. To test this, levels of onfFN in the culture supernatant were measured by an enzyme-linked immunosorbent assay in 18 human lung cancer cell lines. In addition, expressions of onfFN and syndecan-1 mRNA were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 18 lung cancer cell lines, 3 cell lines (all adenocarcinoma) released a significant amount of onfFN in culture supernatants. Of the 18 cell lines tested, 6 cell lines expressed a significant amount of mRNA for onfFN and 4 expressed a significant amount of mRNA for syndecan-1. Levels of onfFN and expressions of mRNA for onfFN and syndecan-1 were consistently higher in non-small cell lung cancer cell lines than in small cell lung cancer cell lines. In addition, cell lines that expressed mRNA for onfFN and syndecan-1 tended to adhere to culture dishes. Syndecan-1 expression was significantly higher in attached cells compared with nonattached cells within the same cell line. Differences in onfFN and syndecan synthesis may explain some in vitro and in vivo characteristics of lung cancer. PMID- 11786734 TI - Inaccuracy of Tl-201 brain SPECT in distinguishing cerebral infections from lymphoma in patients with AIDS. AB - PURPOSE: Studies have suggested using Tl-201 brain SPECT to differentiate lymphoma from infectious processes and to determine the timing for biopsy or empirical therapy for patients with AIDS-related brain lesions. This study prospectively investigated the utility of Tl-201 SPECT in distinguishing central nervous system lymphoma from non-neoplastic disease in patients with AIDS. MATERIALS AND METHODS: Fourteen patients with AIDS and focal abnormalities on computed tomography or magnetic resonance imaging underwent brain SPECT before diagnosis (12 by biopsy, 2 by clinical course and response to therapy). A an uptake ratio (UR) was obtained by drawing a region of interest around the lesion, measuring average counts per pixel, and dividing this value by the value of a non lesion-containing contralateral region of interest. The UR cutoff producing the highest accuracy (TP+TN/TP+TN+FP+FN) in discriminating lymphoma from another condition was determined from URs generated from these 14 patients. RESULTS: Five patients had lymphoma, five had toxoplasmosis, one had Herpes simplex virus encephalitis, two had progressive multifocal leukoencephalopathy, and one had gliosis (UR, 0.8). Patients were separated into categories of lymphoma or nonlymphoma. The mean UR was 2.2 +/- 1.6 (range, 1.0 to 3.85) for lymphoma and 1.7 +/- 0.8 (range, 0.7 to 3.2) for nonlymphoma. Only a UR of 1.63 resulted in sensitivity and specificity better than 50% (60% and 55%, respectively), with an accuracy of 57%, positive predictive value of 43%, and negative predictive value of 71%. CONCLUSIONS: Tl-201 brain SPECT appears unreliable for differentiating primary lymphoma from nonmalignant brain lesions in patients with AIDS. Early brain biopsy is necessary to establish a definitive diagnosis when appropriate. PMID- 11786735 TI - Tc-99m ethylcysteinate dimer brain SPECT perfusion imaging in ictal nonepileptic visual hallucinations. AB - PURPOSE: Visual hallucinations can occur within the central nervous system and may be associated with a lesion anywhere in the visual pathway. The purpose of this study was to assess "ictal" regional cerebral blood flow with Tc-99m ethylcysteinate dimer (ECD) SPECT in patients having acute hallucinations, and to compare the findings to the "interictal" state. METHODS: A prospective study was performed to evaluate patients admitted to the neurology department with nonpsychiatric and nonepileptic visual hallucinations. The nine patients included in the study underwent thorough neurologic and psychiatric evaluations. A computed tomographic (CT) scan was performed when each patient was admitted, and electroencephalographic (EEG) recordings were made during their hallucinations. All patients underwent a brain SPECT while having acute hallucinations (ictal SPECT), and a follow-up scan was obtained 2 to 3 weeks later. RESULTS: All patients had normal ictal EEG findings during the hallucinations. Seven of nine patients had increased perfusion on the SPECT studies in one or more regions, with a mean lesion-to-contralateral ratio of 2.1 (range, 1.5 to 2.7). Three of the seven patients had findings consistent with a cerebrovascular accident. After treatment, the hallucinations disappeared in two patients and the motor deficit improved dramatically. The follow-up SPECT study showed significant improvement in all patients 1 week later. Charles Bonnet syndrome, frontal lobe dementia, and Anton syndrome were diagnosed in three other patients, and the last one had no identifiable background disease, all with normal findings of EEG, CT, and magnetic resonance examinations. They all responded readily to carbamazepine therapy, and the follow-up SPECT study showed resolution of the findings. Two of nine patients showed posterior cortical hypoperfusion, and eventually Lewy body disease was diagnosed. The SPECT showed no evidence of regional hyperperfusion. CONCLUSIONS: This prospective preliminary study suggests that brain imaging using SPECT may be useful in identifying the mechanisms and evolution of blood flow abnormalities in certain subgroups of patients who have visual hallucinations and may assist in the selection of specific therapy. PMID- 11786736 TI - Effect of high specific-activity sulfur colloid preparations on sentinel node count rates. AB - PURPOSE: Preliminary results by other investigators suggest that increasing the specific activity of Tc-99m nanocolloid preparations increases the measured counts in sentinel nodes compared with lower specific-activity (SA) preparations using the same initial injected dose. The authors set out to determine whether a similar result could be perceived with Tc-99m sulfur colloid (SC) preparations. METHODS: Twenty-three consecutive patients (low SA group) with successful visualization of sentinel nodes by lymphoscintigraphy before our standard protocol was changed to a higher SA preparation were compared with 28 patients (high SA group) just after the switch. Injection techniques were similar in both groups: peritumoral injections at two to four points of a mixture of half filtered (0.22 microm filter) and unfiltered Tc-99m sulfur colloid in 6 ml followed immediately by intradermal injections of filtered sulfur colloid above the tumor. Activity levels for both types of injections ranged from 3.7 to 11.1 mBq (100 to 300 microCi). Preparation of the higher SA mixture of sulfur colloid was achieved by using only one eighth of the sulfur colloid vial contents when the same activity (125 mCi) of Tc-99 was added. Regions of interest were drawn around the images of sentinel nodes and the initial injection site in the anterior and lateral projections. Ratios of sentinel node to initial injection site count were calculated for both groups. RESULTS: The mean ratio of sentinel node to injection site count in the high SA group was 2.9 times greater than that in the low SA group. The median ratio value was 2.7 times greater in the high SA group. CONCLUSION: These preliminary results suggest higher counts in the sentinel node are possible with a higher SA preparation. PMID- 11786737 TI - Septal stunning by dipyridamole stress shown on quantitative gated perfusion SPECT in a child with hypertrophic cardiomyopathy. AB - PURPOSE: Myocardial ischemia is an important problem in hypertrophic cardiomyopathy. Stunning is an important mechanism in progressive dysfunction of the ischemic myocardium. In this report, the authors found prolonged myocardial stunning in a child with hypertrophic cardiomyopathy that was induced by dipyridamole stress on quantitative gated SPECT. MATERIALS AND METHODS: A 6-year old boy with septal hypertrophy underwent rest and dipyridamole stress gated myocardial SPECT. Software was used to quantify automatically segmental perfusion and function at rest and after stress. RESULTS: Perfusion imaging showed a reversible perfusion decrease in the hypertrophic septum. Cine-gated imaging of the septum showed dyskinesia and a severe abnormality of systolic thickening during the poststress period, whereas it showed nearly complete recovery at rest. Quantified regional perfusion and function indices also showed this perfusion decrease and myocardial dysfunction after dipyridamole stress. CONCLUSION: In a child with hypertrophic cardiomyopathy, myocardial stunning was induced by dipyridamole stress, in accordance with decreased perfusion reserve. PMID- 11786738 TI - Ga-67 scintigraphy in patients with breast lymphoma. AB - PURPOSE: The authors studied the utility of Ga-67 citrate scintigraphy in patients with breast lymphoma. METHODS: Seven patients with histologically proved breast lymphoma were examined. In three patients, both breasts were involved, and all patients had rapidly growing breast masses. Planar and SPECT images were obtained 72 hours after injection of Ga-67. RESULTS: Ga-67 scintigraphy showed intense accumulation in all lymphomas. SPECT images provided better contrast than did planar images. In one of the seven patients, the axilla and mediastinum were also involved. In six of the seven patients, Ga-67 scintigraphy was also performed after treatment and showed the disappearance of Ga-67 accumulation. In one patient with local recurrence and lung involvement, abnormal accumulation was depicted on follow-up Ga-67 scintigraphy. CONCLUSIONS: Ga-67 scintigraphy was helpful to confirm the diagnosis and the systemic extent of lymphoma and to evaluate the therapeutic effect during follow-up in patients with breast lymphoma. PMID- 11786739 TI - Very early and standard Tc-99m ethyl cysteinate dimer SPECT imaging in a patient with reperfusion hyperemia after acute cerebral embolism. AB - It has been reported that Tc-99m ethyl cysteinate dimer (ECD) SPECT imaging may not show reperfusion hyperemia in patients with subacute stroke. The authors describe a patient with embolic middle cerebral artery occlusion who was examined using xenon-133 and dynamic and standard Tc-99m ECD SPECT immediately after early recanalization. Standard Tc-99m ECD SPECT images revealed hypoactivity in the ipsilateral middle cerebral artery territory. In contrast, the dynamic Tc-99m ECD SPECT images from the first scan (very early images acquired 36 seconds after injection) showed hyperactivity in the same region and provided imaging contrast comparable to what would be obtained with xenon-133 tomography. Hemorrhagic transformation later developed in this region. These results indicate that images from very early dynamic Tc-99m ECD SPECT of areas with irreversible changes produced by acute stroke can reveal reflow hyperemia that standard Tc-99m ECD SPECT images fail to show. PMID- 11786740 TI - Transureteroureterostomy obstruction mimicking acute tubular necrosis. AB - A patient receiving nephrotoxic chemotherapy for metastatic cervical cancer was examined for acute renal failure. A Tc-99m MAG3 scan showed symmetric function, bilateral increasing parenchymal activity, and no tracer excretion in either collecting system. The differential diagnosis included cisplatin-induced nephrotoxicity, dose infiltration, and obstruction of the common ureter. Analysis of the scan, an image over the injection site, and a delayed image of the urinary tract indicated obstruction of the common ureter at the anastomotic site of the transureteroureterostomy. In patients with a transureteroureterostomy, symmetric renal dysfunction, and no bladder activity, a delayed image of the urinary tract should be obtained to distinguish obstruction from acute tubular necrosis. PMID- 11786741 TI - Compensatory uptake of I-123 MIBG in the contralateral adrenal gland after removal of a pheochromocytoma. AB - The identification of recurrent or residual tumor tissue is sometimes complicated. The authors describe a 53-year-old woman in whom I-123 metaiodobenzylguanidine (MIBG) scintigraphy revealed a pheochromocytoma in the right adrenal gland. After the tumor was removed, the patient's catecholamine levels normalized. At the 3-month follow-up examination, I-123 MIBG scintigraphy did not reveal uptake in the right adrenal region but rather showed uptake in the left adrenal region. The patient's blood pressure remained in the normal range. A third scintigram, obtained 1 year after tumor resection, no longer detected I-123 MIBG accumulation in the left adrenal gland. These findings suggest that compensatory hyperplasia of the left adrenal gland led to enhanced uptake of I 123 MIBG. They also highlight the need for careful follow-up of such patients to distinguish between physiologic and pathologic processes. PMID- 11786742 TI - Applications of nuclear medicine in pediatric oncology. AB - Nuclear medicine is important in the diagnosis, staging, and long-term surveillance of a number of pediatric cancers. Skeletal scintigraphy is used to evaluate primary skeletal cancers, such as osteosarcoma and Ewing sarcoma, and nonskeletal cancers such as neuroblastoma, lymphoma, medulloblastoma, rhabdomyosarcoma, and retinoblastoma. Metaiodobenzylguanidine scintigraphy is valuable in examinations of children with neuroblastoma. The therapeutic response of primary bone and brain tumors can be assessed using Tl-201 and Tc-99m MIBI scintigraphy. Imaging strategies for staging and monitoring the therapeutic response of Hodgkin's lymphoma include Ga-67 citrate scintigraphy. Pediatric oncologic applications of positron emission tomography are being investigated extensively. PMID- 11786743 TI - Vertebral hemangioma demonstrated by Tc-99m DTPA-human serum albumin SPECT. PMID- 11786744 TI - FDG positron emission tomographic imaging of the effect of an intrauterine device. PMID- 11786745 TI - Postinfectious encephalitis: a coregistered SPECT and magnetic resonance imaging study. PMID- 11786746 TI - Improvement in cold-induced Raynaud's syndrome with administration of ticlopidine hydrochloride detected by Tc-99m DTPA human serum albumin scintigraphy. PMID- 11786747 TI - High F-18 FDG uptake in a paraspinal textiloma. PMID- 11786748 TI - Calcified "Sister Mary Joseph" umbilical metastasis from ovarian cystadenocarcinoma seen on an MDP bone scintigram. PMID- 11786749 TI - Focal F-18 FDG uptake in a nontoxic autonomous thyroid nodule. PMID- 11786750 TI - False-positive blood pooling adjacent to hepatic malignant fibrous histiocytoma on Tc-99m RBC liver SPECT. PMID- 11786751 TI - Granulocyte colony-stimulating factor: confounding F-18 FDG uptake in outpatient positron emission tomographic facilities for patients receiving ongoing treatment of lymphoma. PMID- 11786752 TI - F-18 FDG positron emission tomography demonstrates resolution of non-Hodgkin's lymphoma of the parotid gland in a patient with Sjogren's syndrome: before and after anti-CD20 antibody rituximab therapy. PMID- 11786753 TI - Ga-67 scintigraphic findings in a case of multicentric reticulohistiocytosis. PMID- 11786754 TI - Mobilization of the rectum: anatomic concepts and the bookshelf revisited. AB - INTRODUCTION: Sound surgical technique is based on accurate anatomic knowledge. In surgery for cancer, the anatomy of the perirectal fascia and the retrorectal plane is the basis for correct mobilization of the rectum to ensure clear surgical margins and to minimize the risk of local recurrence. METHODS: This review of the literature on the perirectal fascia is based on a translation of the original description by Thoma Jonnesco and a later account by Wilhelm Waldeyer. The Jonnesco description, first published in 1896 in French, is compared with the German account of 1899. These were critically analyzed in the context of our own and other techniques of mobilizing the rectum. CONCLUSIONS: Mobilization of the rectum for cancer can be performed along anatomic planes with minimal blood loss, preservation of the pelvic autonomic nerves and a low prevalence of local recurrence. Different techniques including total mesorectal excision are based on the same anatomic principles, however, popular words have been used to replace accepted, established terminology. In particular, the description of total mesorectal excision has been confusing because of its emphasis on the words "total" and "mesorectum." The use of the word "mesorectum" anatomically is inaccurate and the implication that total excision of all the perirectal fat contained within the perirectal fascia "en bloc" in all patients with rectal cancer will minimize local recurrence remains contentious. PMID- 11786756 TI - Accuracy of endorectal ultrasonography in preoperative staging of rectal tumors. AB - PURPOSE: Preoperative staging of rectal tumors is considered essential to tailor treatment for individual patients. The aim of the present study was to evaluate the accuracy of endorectal ultrasonography in preoperative staging of rectal tumors. METHODS: Eleven hundred eighty-four patients with rectal adenocarcinoma or villous adenoma underwent endorectal ultrasonography evaluation at a single institution during a ten-year period. We compared the endorectal ultrasonography staging with the pathology findings based on the surgical specimens in 545 patients who had surgery (307 by transanal excision, 238 by radical proctectomy) without adjuvant preoperative chemoradiation. Comparisons between groups were performed using chi-squared tests and logistic regression analysis. RESULTS: Overall accuracy in assessing the level of rectal wall invasion was 69 percent, with 18 percent of the tumors overstaged and 13 percent understaged. Accuracy depended on the tumor stage and on the ultrasonographer. Overall accuracy in assessing nodal involvement in the 238 patients treated with radical surgery was 64 percent, with 25 percent overstaged and 11 percent understaged. CONCLUSION: The accuracy of endorectal ultrasonography in assessing the depth of tumor invasion, particularly for early cancers, is lower than previously reported. The technique is more precise in distinguishing between benign tumors and invasive cancers and between tumors localized to the rectal wall and tumors with transmural invasion. Differences in image interpretation may in part explain discrepancies in accuracy between studies. PMID- 11786758 TI - Endoanal ultrasound in the staging and management of squamous-cell carcinoma of the anal canal: potential implications of a new ultrasound staging system. AB - PURPOSE: This study was performed to determine whether endoanal ultrasound could be used to accurately stage patients with squamous-cell carcinoma of the anal canal and to determine the response of these tumors to multimodality therapy. METHODS: Thirteen consecutive patients with biopsy-proven squamous-cell carcinoma of the anal canal between 1996 and 1999 were included in the study. All patients underwent a pretreatment staging endoanal ultrasound with a B&K 3535 ultrasound machine using the 1850 rotating 360 degrees probe with a 10-MHz transducer. Tumors were staged using our own modification of a 1984 TNM staging system. For our study, a uT1 tumor was confined to the submucosa; a uT2a lesion invaded only the internal anal sphincter; a uT2b lesion penetrated into the external anal sphincter; a uT3 lesion invaded through the sphincter complex into the perianal tissues; and a uT4 lesion invaded adjacent structures. After the initial study, patients decided on a course of treatment, either primary surgery or chemoradiation. For patients choosing chemoradiation, a clinical examination with biopsies and a repeat endoanal ultrasound was performed after completion of therapy. Findings on physical examination and biopsy results were compared with the follow-up endoanal ultrasound. For those choosing surgery, the pathology specimen from the abdominoperineal resection was reviewed and compared with the initial endoanal ultrasound interpretation to determine the accuracy of endoanal ultrasound staging. RESULTS: One patient died of complications from acquired immunodeficiency syndrome before undergoing definitive treatment for his anal cancer. Of the remaining 12 patients who comprised the study, the endoscopic staging was as follows: 1 uT1, 5 uT2a, 3 uT2b, 2 uT3, and 1 uT4. Five of the 12 patients selected surgery as the primary treatment modality for their disease. The other seven patients underwent a full course of chemoradiation. In all five patients who had an abdominoperineal resection, the surgical staging correlated with the endoanal ultrasound staging (2 T2a tumors and 3 T2b tumors). In the remaining seven patients, six to eight weeks after completion of therapy, there was no evidence of residual tumor by clinical examination and biopsies. In one of the seven patients, no abnormalities were detected on endoanal ultrasound, and it was interpreted as normal with no evidence of disease. In the remaining six patients, endoanal ultrasound revealed abnormalities that were judged to represent radiation-induced changes rather than residual disease. A repeat endoanal ultrasound was done in these patients two to four months after the biopsies. Complete resolution of the postradiation changes occurred in all patients, and the scans were interpreted as showing no evidence of disease. CONCLUSIONS: Endoanal ultrasound can accurately determine the depth of penetration of squamous-cell carcinoma into the sphincter complex and can be used to gauge accurately the response of these tumors to chemoradiation therapy. Our newly proposed ultrasound staging system may be more useful in choosing treatment options; future studies should be aimed at using endoanal ultrasound in identifying early lesions that may be amenable to less aggressive therapy as well as determining the utility of ultrasound in the surveillance of patients after successful treatment of their initial tumors. PMID- 11786759 TI - Simultaneous detection of colonic epithelial cells in portal venous and peripheral blood during colorectal cancer surgery. AB - PURPOSE: This study was designed to show, in certain patients, that colonic epithelial cells can be present in peripheral blood while absent in portal venous blood. METHODS: The circulating colorectal epithelial cells were detected by a reverse transcriptase-polymerase chain reaction assay, which involved amplifying guanylyl cyclase C transcripts. Portal venous and peripheral blood samples were obtained at intervals from 58 patients undergoing colorectal cancer surgery. RESULTS: Circulating colonic epithelial cells were more frequently detected in portal venous blood than in peripheral blood only before mobilization of the tumor-bearing colon segment in patients with tumors of Stage B. In five other patients, before mobilization of their tumor-bearing colon segments, and in another three patients, during the mobilization, colorectal epithelial cells were detected in peripheral blood but not in portal venous blood. These eight patients had Stage C or D tumors. CONCLUSION: In 8 of 58 patients, colorectal epithelial cells were detected in peripheral but not in portal venous blood. Metastatic deposits in lymphatic vessels or liver might be the source of these cells. PMID- 11786761 TI - Quality of life after ileal pouch-anal anastomosis: an evaluation of diet and other factors using the Cleveland Global Quality of Life instrument. AB - PURPOSE: Although functional results after ileal pouch-anal anastomosis are excellent, imperfections of function do occur. In this setting, quality-of-life assessment is an invaluable tool in determining overall therapeutic efficacy. We evaluated the impact of dietary restrictions, preoperative diagnosis (ulcerative colitis vs. familial adenomatous polyposis), and pregnancy (after pouch insertion) on quality of life. METHODS: After ethical approval, 64 patients were reviewed (mean age, 31 (range, 15-54) years). Long-term quality of life in patients after ileal pouch-anal anastomosis was assessed using the Cleveland Global Quality of Life instrument or Fazio score. The Cleveland Global Quality of Life score is a novel quality-of-life instrument specifically designed for patients with ileal pouches. Stool frequency and continence were recorded to establish the functional status of this group. RESULTS: Sixty-one patients (95.3 percent) complained of some form of dietary restriction and adopted a fixed dietary regimen. All such patients felt that a breach of this regimen would impinge significantly on their quality of life. Late eating and alcohol were associated with diarrhea, whereas smoking was not. Constipation was infrequently reported. The mean Cleveland Global Quality of Life score of patients with ulcerative colitis (0.81 +/- 0.13) was greater than that of patients with ulcerative colitis and a background of pouchitis (0.78 +/- 0.16; P = 0.042). Whereas postoperative stool frequency in patients with familial adenomatous polyposis was always higher than the preoperative level (4 vs. 2 movements per day; P = 0.04), the Cleveland Global Quality of Life score of this group was lower than that of ulcerative colitis patients (0.77 vs. 0.81; P = 0.047). The Cleveland Global Quality of Life score of females who had had pregnancies after pouch formation was 0.70, significantly lower (P = 0.039) than that of ulcerative colitis patients, although pouch function was similar to the general group (7 vs. 6 daily bowel movements with full continence in all parous patients). CONCLUSIONS: Most patients suffered dietary restrictions, forcing them to adopt a fixed dietary regimen. Breach of this regimen would impact on their quality of life. Hence composition of diet and timing of intake are important determinants of quality of life after ileal pouch formation. Patients with familial adenomatous polyposis and those with a history of pouchitis had poorer Cleveland Global Quality of Life scores than ulcerative colitis patients without a background of pouchitis. This indicates that they also had poorer quality of life. Parous patients had the lowest Cleveland Global Quality of Life scores, indicating the poorest quality of life. These differences did not correlate with poorer pouch function, highlighting the influence of non-pouch-related factors in quality of life after ileal pouch formation. PMID- 11786762 TI - Endosonographic evidence of persistence of Crohn's disease-associated fistulas after infliximab treatment, irrespective of clinical response. AB - PURPOSE: Infliximab has been reported to improve fistulizing Crohn's disease. Moreover, prompt healing of mucosal ulcers has been described. Whether fistulas disappear or remainders of fistulas persist is unknown. This study documents fistulous tracts before and after infliximab therapy by means of hydrogen peroxide-enhanced endosonography METHODS: Eight patients with perianal, vaginal, or perineal fistulas were treated with a triplet of infliximab 5 mg/kg infusions. At baseline, and at Week 4 after the last infusion, fistulas were documented by local inspection, digital examination, and hydrogen peroxide-enhanced anal or vaginal endosonography. RESULTS: Patients with vaginal or perineal fistulas did not respond clinically to therapy, whereas patients with perianal fistulas improved considerably. However, in all patents remainders of fistulous tracts were demonstrated by endosonographic techniques. CONCLUSIONS: Short-term treatment of Crohn's disease-associated fistulas with infliximab does not induce disappearance of fistulous tracts, irrespective of therapeutic response. PMID- 11786764 TI - Segmental resection or subtotal colectomy in Crohn's colitis? AB - PURPOSE: Segmental resection for Crohn's colitis is controversial. Compared with subtotal colectomy, segmental resection is reported to be associated with a higher rate of re-resection. Few studies address this issue, and postoperative functional outcome has not been reported previously. This study compared segmental resection to subtotal colectomy with anastomosis with regard to re resection, postoperative symptoms, and anorectal function. METHODS: Fifty-seven patients operated on between 1970 and 1997 with segmental resection (n = 31) or subtotal colectomy (n = 26) were included. Reoperative procedures were analyzed by a life-table technique. Segmentally resected patients were also compared separately with a subgroup of subtotally colectomized patients (n = 12) with similarly limited colonic involvement. Symptoms were assessed according to Best's modified Crohn's Disease Activity Index and an anorectal function score. RESULTS: The re-resection rate did not differ between groups in either the entire study population (P = 0.46) or the subgroup of patients with comparable colonic involvement (P = 0.78). Segmentally resected patients had fewer symptoms (P = 0.039), fewer loose stools (P = 0.002), and better anorectal function (P = 0.027). Multivariate analysis revealed the number of colonic segments removed to be the strongest predictive factor for postoperative symptoms and anorectal function (P = 0.026 and P = 0.013, respectively). CONCLUSION: Segmental resection should be considered in limited Crohn's colitis. PMID- 11786765 TI - Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. AB - PURPOSE: Several alterations of the enteric nervous system have been described as an underlying neuropathologic correlate in patients with idiopathic slow-transit constipation. To obtain comprehensive data on the structural components of the intramural nerve plexus, the colonic enteric nervous system was investigated in patients with slow-transit constipation and compared with controls by means of a quantitative morphometric analysis. METHODS: Resected specimens were obtained from ten patients with slow-transit constipation and ten controls (nonobstructive neoplasias) and processed for immunohistochemistry with the neuronal marker Protein Gene Product 9.5. The morphometric analysis was performed separately for the myenteric plexus and submucous plexus compartments and included the quantification of ganglia, neurons, glial cells, and nerve fibers. RESULTS: In patients with slow-transit constipation, the total ganglionic area and neuronal number per intestinal length as well as the mean neuron count per ganglion were significantly decreased within the myenteric plexus and external submucous plexus. The ratio of glial cells to neurons was significantly increased in myenteric ganglia but not in submucous ganglia. On statistical analysis, the histopathologic criteria (submucous giant ganglia and hypertrophic nerve fibers) of intestinal neuronal dysplasia previously described in patients with slow transit constipation were not completely fulfilled. CONCLUSION: The colonic motor dysfunction in slow-transit constipation is associated with quantitative alterations of the enteric nervous system. The underlying defect is characterized morphologically by oligoneuronal hypoganglionosis. Because the neuropathologic alterations primarily affect the myenteric plexus and external submucous plexus, superficial submucous biopsies are not suitable to detect these innervational disorders. PMID- 11786766 TI - Anal continence after rectocele repair. AB - INTRODUCTION: Rectocele may be associated with both chronic constipation and anal incontinence. Several different surgical procedures have been advocated for rectocele repair. The aim of the present study was to evaluate anorectal function and clinical outcome in a consecutive series of patients who underwent selected endorectal or transperineal surgery for rectocele for whom operative treatment was determined by clinical and proctographic features. Attention was paid to the cohort of rectocele patients presenting with incontinence as a leading symptom. METHODS: Sixty consecutive patients with symptomatic rectocele underwent surgical treatment at our institution. Fifty-eight of the patients were female (mean age 56; range, 21-70 years). Incontinence was graded according to a previously reported scoring system that accounts for the type and frequency of incontinence episodes. Preoperative anorectal manometry was performed using an open perfused polyethylene probe. Rectal sensation was recorded by balloon distention. Endoanal ultrasonography was performed with a 7.5-MHz probe. Preoperative defecography was performed at rest and on maximal squeeze and straining. Patients with obstructed defecation as their principal symptom, with associated mucosal rectal prolapse, underwent an endorectal procedure. For patients with associated anal incontinence (Grade B2 or greater), and without a rectal mucosal prolapse, a transperineal approach was performed with either an anterior external overlapping sphincteroplasty or levatorplasty. The median follow-up was 48 (range, 9-122) months. RESULTS: There was no operative mortality. Postoperative complications occurred in 18 patients (30 percent). Of 43 patients with incontinence, 34 (79 percent) were available for postoperative evaluation. None were fully continent. However, in 25 patients (73.5 percent), continence improved after surgery; half had only mucus soiling or loss of gas. Incontinence scores decreased (i.e., improved) from 4.8 +/- 0.9 to 3.9 +/- 0.9 (P = 0.002). A significant improvement was found both after transanal and perineal procedures. Only ten initially continent patients were available for postoperative assessment. All patients stated that they had clinical improvement in constipation. Their preoperative mean anal resting pressure was 62.5 +/- 3.9 (standard error of the mean) mmHg, with a postoperative mean of 75.5 +/- 7 mmHg. The preoperative mean squeeze pressure was 83.1 +/- 8.5 mmHg, with a mean postoperative squeeze pressure of 88.5 +/- 7.9 mmHg (P = not significant). The maximal tolerable volumes were all within normal limits, confirming the proctographic evidence that there were no cases of megarectum in our patient series. The pudendal nerve terminal motor latency was abnormal in all but two patients with incontinence (mean pudendal nerve terminal motor latency = 3.1; range, 1.2-4 milliseconds). Rectoceles recurred in six patients (10 percent): five after a Block procedure and one after a Sarles-type operation. The postoperative endosonographic appearance varied according to the nature of the procedure performed. CONCLUSION: There are few data concerning patients with rectocele who have associated anal incontinence, however, surgical decision analysis resulted in improvement in both constipation and incontinence in the majority of our patients with rectocele. Nevertheless, because none of the patients gained full continence postoperatively, pelvic floor rehabilitation might be also needed to achieve better sphincter function in patients with incontinence. PMID- 11786767 TI - Hemorrhoidectomy: open or closed technique? A prospective, randomized clinical trial. AB - PURPOSE: Hemorrhoidectomy is the treatment of choice for patients with third degree or fourth-degree hemorrhoids. However, whether the closed or open technique yields better results is unknown. The purpose of this study was to compare these techniques with respect to operating time, analgesic requirement, hospital stay, morbidity rate, duration of inability to work, healing time, and follow-up results. METHODS: In this prospective and randomized study, 80 patients with third- degree or fourth-degree hemorrhoidal disease were allocated to either the open- hemorrhoidectomy (Group A, n = 40) or the closed-procedure group (Group B, n = 40). Open hemorrhoidectomy was performed according to the St. Mark's Hospital technique, whereas the Ferguson technique was used for the closed procedure under general anesthesia with the patient in the jackknife position. RESULTS: Mean operating time was significantly shorter in Group A (35 +/- 7 vs. 45 +/- 8 minutes, P < 0.001). Analgesic requirement on the day of surgery and the first postoperative day was also significantly lower (P < 0.05). The morbidity rate was higher in Group B (P < 0.05). Length of hospital stay and duration of inability to work were similar in both groups (P > 0.05). Healing time was significantly shorter in Group B (2.8 +/- 0.6 vs. 3.5 +/- 0.5 weeks, P < 0.001). Median follow-up time was 19.5 (range, 4-40) months. The only late complication (anal stenosis) was observed in one patient in Group B. CONCLUSIONS: Although the healing time is longer, the open technique is more advantageous with respect to shorter operating time, less discomfort in the early postoperative period, and lower morbidity rate. PMID- 11786768 TI - Small colonic J-pouch improves colonic retention of liquids--randomized, controlled trial with scintigraphy. AB - PURPOSE: A small 6-cm colonic J-pouch improves stool frequency and continence, without stool evacuation problems. However, the reservoir function is not improved on physiologic studies. Hence, a scintigraphy technique was devised to study the transit of solid and liquid colonic contents in these patients. METHODS: Patients were randomly assigned to straight or colonic J-pouch anal anastomoses after ultralow anterior resection. At 1 year after surgery, they were studied by bowel questionnaire, anorectal manometry, and technetium TC 99m tin colloid liquid test meal/I-131 microcapsule scintigraphy. In the latter, technetium TC 99m tin-colloid was ingested orally to image the colonic liquids. I 131 microcapsules taken simultaneously imaged the solid stools. After ingestion of the radioisotopes, imaging was performed at intervals of 7 to 8, 24, and 56 hours later. Two independent observers noted the presence of technetium TC 99m tin-colloid liquid and I-131 microcapsules in various areas of interest drawn over the colon. RESULTS: There were six patients (5 males, mean age, 61.5 (SE mean, 1.9) years) in the straight, and six patients (5 males, mean age, 63.2 (4.5) years) in the colonic J-pouch group. Stool frequency was more in the straight group (4.8 (0.4) vs. 3 (0.2) stools/day; P <.001). Continence, evacuation problems, and anorectal physiologic findings were not different. Technetium TC 99m tin-colloid (imaging liquids) transited significantly faster than I-131 microcapsules (imaging solids), at various areas of interest in the colon. In the colonic J-pouch patients, technetium TC 99m tin-colloid liquid was retained significantly longer in the descending colon at 24 hours (P <.05). Stool frequency was higher when technetium TC 99m tin-colloid was not retained in the descending colon at 56 hours (3.3 (0.5) vs. 4.3 (0.4) stools/day) but this did not reach statistical significance. There were no significant differences in the distribution of the ingested I-131 microcapsules between colonic J-pouch and straight groups. CONCLUSIONS: Reduced stool frequency after colonic J-pouch may be related to factors causing better retention of liquid stools in the distal colon. No difference in solid stool transit could possibly account for minimal evacuation problems in small pouches. PMID- 11786769 TI - Strength-duration testing of the external anal sphincter in females with anorectal dysfunction. AB - PURPOSE: The strength-duration test has been suggested as a means of assessing external anal sphincter function. This study was designed to investigate this claim by comparing the strength-duration test with established measures of external anal sphincter function. METHODS: Forty-nine females undergoing diagnostic anorectal testing (manometry, rectal sensation, electromyogram, pudendal nerve terminal motor latency, and endoanal ultrasound) also had the strength-duration test performed (which was repeated for each patient after a short rest period). RESULTS: The strength-duration test was repeatable. Statistically significant correlations were found between this test at pulse durations of 3 ms, 1 ms, and 0.3 ms with electromyographic activity of the external anal sphincter and with pressure in the anal canal during voluntary contraction. Significant correlations were found for durations of 100 ms, 30 ms, 10 ms, and 3 ms with the pudendal nerve terminal motor latency on the right and for the 3 ms and 0.3 ms durations with latency on the left. There were no correlations between the strength-duration test and resting pressure in the anal canal. CONCLUSION: The strength-duration test significantly correlates with the established measures of external anal sphincter function and its innervation. Therefore, this simple test appears to provide a simple measure of external anal sphincter denervation. PMID- 11786770 TI - Risk of second cancers in patients with colorectal carcinoids. AB - INTRODUCTION: It is often stated that patients with colorectal carcinoid tumors have an increased risk of developing other malignancies. However, this risk has not been conclusively documented. A comprehensive evaluation is needed to more thoroughly assess the risk of second cancers in patients with colorectal carcinoids. METHODS: A search of the National Cancer Institute Surveillance, Epidemiology, and End Result database from 1973 to 1996 revealed 2,086 patients with colorectal carcinoids. This subset of patients was examined for occurrence of second cancers. The observed incidence of cancer for each site was compared with the expected incidence based on the gender-adjusted and age-adjusted cancer rates in the remaining Surveillance, Epidemiology, and End Result file. A Poisson distribution probability was used to determine the significance of these comparisons. RESULTS: Patients with colorectal carcinoids had an increased rate of cancer in the colon and rectum (P < 0.001), small bowel (P < 0.001), esophagus/stomach (P = 0.02), lung/bronchus (P < 0.001), urinary tract (P = 0.005), and prostate (P < 0.001), when compared with a control population. Most of the gastrointestinal tract cancers were synchronous cancers, whereas lesions outside the gastrointestinal tract were most commonly metachronous tumors. CONCLUSIONS: A significantly increased risk of synchronous colorectal, small bowel, gastric, and esophageal cancers and metachronous lung, prostate, and urinary tract neoplasms is clearly demonstrated. After the diagnosis of colorectal carcinoid tumors, patients should undergo appropriate screening and surveillance for cancer at these sites. PMID- 11786771 TI - Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. AB - PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase 2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer. PMID- 11786772 TI - Local infiltration with ropivacaine improves immediate postoperative pain control after hemorrhoidal surgery. AB - PURPOSE: This study was conducted to assess the efficacy of infiltration with a new local anesthetic (ropivacaine) to control pain after hemorrhoidal surgery. METHODS: Thirty-four patients who underwent hemorrhoidectomy were included in a double-blind, randomized study to assess the analgesic effect of a perianal infiltration with 40 ml of 0.75 percent ropivacaine compared with isotonic saline infiltration. Postoperatively, pain was assessed on a visual analog scale, and intravenous morphine consumption was measured with patient-controlled administration. RESULTS: In the ropivacaine group, patients had lower visual analog scale scores at 1, 3, and 6 hours after infiltration and required fewer cumulative doses of morphine (patient-controlled administration) at 3, 6, and 12 hours. Side effects were comparable in the two groups. CONCLUSION: Local infiltration with ropivacaine improves pain control and patient comfort in the immediate postoperative course of hemorrhoidal surgery. PMID- 11786773 TI - Ileojejunal transposition delays gastric emptying and decreases fecal water content in dogs with total colectomy. AB - PURPOSE: The aim of the study was to investigate the effect of ileojejunal transposition, in which the distal ileum is interposed isoperistaltically into the proximal jejunum, on gastric emptying, gastrointestinal motility, and fecal water content in dogs with total colectomy. METHODS: Dogs were divided into three groups: dogs with intact colons (control), total colectomy alone (sham operated group), or total colectomy and ileojejunal transposition group. The alimentary tract was reconstructed by ileal J-pouch-rectal anastomosis. Gastric emptying was measured by a validated freeze-drying method, and gastrointestinal motility was measured by strain gauge force transducers. Plasma peptide YY was measured by specific radioimmunoassay. Fecal water content was measured in dogs with total colectomy. RESULTS: Gastric emptying of solids in the ileojejunal transposition group was delayed longer than 120 minutes after meal ingestion compared with that in the sham operated group. The duration of the digestive state was prolonged in the ileojejunal transposition group, only when compared with the control group. Plasma peptide YY was increased in the ileojejunal transposition group compared with the sham operated group. Fecal water content was decreased in the ileojejunal transposition group compared with the sham operated group. CONCLUSIONS: Ileojejunal transposition delays gastric emptying of solids and decreases fecal water content in dogs with total colectomy, indicating that ileojejunal transposition might be able to improve intractable watery diarrhea after total colectomy. PMID- 11786775 TI - Gossypiboma--"a surgeon's legacy": report of a case and review of the literature. AB - Gossypiboma (from Latin gossipium cotton and Kiswahili boma place of concealment) or retained surgical sponge is a ubiquitous medical error that is avoidable. It can cause serious morbidity and possibly even mortality. Because it is not anticipated, it is frequently misdiagnosed, and often-unnecessary radical surgical procedures are performed. It should be considered in the differential diagnosis of any postoperative case with unresolved or unusual problems. PMID- 11786776 TI - Formalin instillation for control of rectal hemorrhage in advanced pelvic malignancy: report of two cases. AB - PURPOSE: This article describes the use of intrarectal formalin to treat intractable rectal bleeding from pelvic malignancy. METHODS: Case reports of two patients with intractable rectal bleeding from pelvic malignancy are described. RESULTS: In both cases, treatment with intrarectal formalin stopped the rectal bleeding. CONCLUSION: Formalin instillation into the rectum is an invaluable technique when one is faced with rectal hemorrhage from inoperable pelvic tumors. PMID- 11786777 TI - Lymphocytic colitis treated with proctocolectomy and ileal J-pouch-anal anastomosis: report of a case. AB - PURPOSE: We present a case of severe diarrhea caused by lymphocytic colitis and concurrent celiac sprue in a patient who did not respond to maximal medical therapy and required surgery. METHODS: The patient was initially treated with fecal diversion via an end ileostomy. Six months later, she underwent colectomy and one-stage ileal J-pouch-anal anastomosis. RESULTS: Notably, the characteristic microscopic changes of lymphocytic colitis were still present at the time of colectomy despite diversion. CONCLUSION: Colectomy with continent reconstruction is an option for treatment of patients with lymphocytic colitis refractory to medical therapy. PMID- 11786778 TI - Attenuated familial adenomatous polyposis: an evolving and poorly understood entity. AB - PURPOSE: Familial adenomatous polyposis is a well-described, autosomal dominant, inherited syndrome characterized by diffuse polyposis of the colon and rectum as well as various upper gastrointestinal and extraintestinal manifestations. A subset of patients present with fewer colorectal polyps, later age of onset of polyps and cancer, and a predilection toward involvement of the proximal colon. This variant of familial adenomatous polyposis is known as attenuated familial adenomatous polyposis. The purpose of this review is to summarize current knowledge regarding this poorly understood entity and propose guidelines for diagnosis, surveillance, and surgical management. METHODS: The MEDLINE database was searched from 1985 onward using the keywords, "attenuated familial adenomatous polyposis," "AFAP," "adenomatous polyposis coli gene," and "APC gene." Additional articles were identified through the reference sections of retrieved papers. All papers that pertained to attenuated familial adenomatous polyposis or mutations in the APC gene producing an attenuated phenotype were included. RESULTS: Attenuated familial adenomatous polyposis is transmitted in an autosomal dominant fashion. Several distinct mutations within the APC gene have been associated with an attenuated phenotype, but variability of disease expression within kindreds possessing identical mutations makes classification difficult. Polyps are diagnosed at a mean age of 44 years, with cancer diagnosed at a mean of 56 years of age. Frequent involvement of the proximal colon necessitates the use of colonoscopy for surveillance, and infrequent involvement of the rectum supports the role of a total abdominal colectomy and ileorectal anastomosis. CONCLUSIONS: Although currently recognized as a distinct clinical entity, attenuated familial adenomatous polyposis may be part of a spectrum of disease that includes familial adenomatous polyposis and is caused by different mutations within the APC gene. Because of its unique characteristics, yet apparent overlap with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, increased awareness of attenuated familial adenomatous polyposis should improve diagnosis, surveillance, and treatment strategies in this unique subset of familial polyposis syndromes. PMID- 11786780 TI - Use of a mattress suture to eliminate dog ears in double-stapled and triple stapled anastomoses. AB - Double-stapling techniques for restorative rectal resection have been effective in minimizing local contamination compared with open circular stapling techniques. Inclusion of the transverse staple line closure of the distal rectal stump in the circular stapled anastomosis may minimize the risk of suture line recurrence. A technique for formation of such an anastomosis is described that avoids use of a distal purse string. PMID- 11786781 TI - Controlled tamponade of severe presacral venous hemorrhage: use of a breast implant sizer. AB - Hemorrhage from the presacral venous plexus is a potentially life-threatening complication of pelvic operations. The morbidity and mortality that stems from severe hemorrhage has led to the development of various hemostatic techniques. Although suture ligature, packing, and placement of tacks can be very effective, they can often be unsuccessful. When these conventional hemostatic techniques fail, alternative approaches are required. We describe the successful use of an expandable breast implant sizer and outline the practical, theoretical, and financial advantages of applying this technique when more conservative approaches have failed. PMID- 11786782 TI - Preoperative neoadjuvant therapy for rectal cancer also enables autologous transfusion. PMID- 11786783 TI - The prevalence of negative studies with inadequate statistical power: an analysis of the plastic surgery literature. AB - Studies published in the medical literature often neglect to consider the statistical power needed to detect a meaningful difference between study groups. Small sample sizes tend to produce negative results because of low statistical power. Studies that cannot make conclusive statements about their hypotheses can waste resources, deter further research, and impede advances in clinical treatment. The current study reviewed three of the most frequently read plastic surgery journals from 1976 to 1996 to determine the prevalence of inadequately (<80 percent) powered clinical trials and experimental studies that found no difference (negative studies) in the response variable of interest between comparison groups. The statistical power of 54 negative studies using continuous response variables was calculated to detect a difference of 1 SD (+/-1 SD) in means between the comparative groups. The power of another 57 negative studies with dichotomous response (yes/no) variables was calculated to detect a relative change in proportions of 25 percent and 50 percent from the experimental to the control group. It was found that 85 percent of the studies with continuous response variables had inadequate power to detect the desired mean difference of +/-1 SD. In studies with dichotomous response variables, 98 percent had inadequate power to detect a desired 25 percent relative change in proportions, and 74 percent had inadequate power to detect a desired 50 percent relative change in proportions. These results indicate that many of the studies in the plastic surgery literature lack adequate power to detect a moderate-to-large difference between groups. The lack of power makes the interpretation of the studies with negative findings inconclusive. Proper study design dictates that investigators consider a priori the difference between groups that is of clinical interest, and the sample size per group that is needed to provide adequate statistical power to detect the desired difference. PMID- 11786785 TI - After plastic surgery: adolescent-reported appearance ratings and appearance related burdens in patient and general population groups. AB - The aim of this study was to determine the effects of appearance-related surgery on psychosocial functioning during adolescence. To this end, changes in bodily attitudes and appearance-related burdens in adolescents undergoing corrective (for aesthetic deformities) and reconstructive (for congenital or acquired deformities) surgery were compared with those in a general population sample.A group of 184 adolescent plastic surgery patients (corrective, n = 100; reconstructive, n = 84), and a comparison group of 83 adolescents at random selected from three municipalities (corrective, n = 67; reconstructive, n = 16), aged 12 to 22 years, were studied at two time points with a 6-month interval. The plastic surgical patients were studied presurgically and postsurgically. Using fully structured telephone interviews and postal questionnaires, adolescents' ratings of their appearance, bodily satisfaction and attitudes, and appearance related burdens were obtained. All patients reported a significant decrease in burdens after surgery compared with the comparison group, indicating a much more prominent improvement in the patient sample compared with the developmental changes that may be expected to occur in adolescence. The corrective patient group reported least burdens after the operation. More specifically, the "breasts" group benefited most from the operation, indicating that breast corrections are rewarding interventions. The findings of this study imply that adolescents can be regarded as good candidates for plastic surgery. They gain bodily satisfaction, and they are relieved of many appearance-related burdens. Physical, social, and psychological burdens related to appearance satisfaction improve considerably in both corrective and reconstructive adolescent patients. PMID- 11786786 TI - Psychological impact of traumatic injuries: what the surgeon can do. AB - In their treatment of accident and assault victims, plastic surgeons have unique opportunities to identify and refer patients with posttraumatic stress symptoms. This article describes brief assessments that surgeons or their clinic staff can use to evaluate traumatically injured adults and children for trauma-related psychological symptoms. An immediate postinjury evaluation (within 10 days of the trauma) consists of 11 questions to determine the presence of the following risk factors for posttrauma maladjustment: panic during or immediately after the trauma, reexperiencing symptoms, avoidance, sleep disturbance, injury from an assault, previous trauma and psychiatric history, and blaming someone else for the injury. The seven follow-up interview questions assess reexperiencing symptoms, avoidance, trauma-related phobias, depression, irritability, and increased substance use, all of which, if present, suggest psychological impairment. Questions recommended for the evaluation of younger children assess changes in play and recreational activity, sleep disturbance, night terror, aggression, irritability, avoidance, emergence of new fears, and loss of recently acquired developmental skills. The assessments require less than 2 minutes and are easily integrated into the hospital or clinic examinations of these patients. PMID- 11786787 TI - The subunit approach to nasal tip hemangiomas. AB - Many surgeons who operate on nasal tip hemangiomas find a central vertical scar frustrating. Alternatives such as open rhinoplasty provide great exposure, but the redraping leaves unsightly scars along the alar rim and columella. Therefore, a new aesthetic incision was needed to allow hemangioma reduction in both the horizontal and vertical dimensions while providing adequate access to the lower lateral cartilage for soft-tissue reduction and/or suturing. The subunit incision, based on the pioneering work of Burget and Menick, was developed to provide both excellent exposure and cosmesis. By designing the incision to lie along the contour lines of the nasal subunits, the senior author (B.M.Z.) believed that the border scars would reflect lines of light and cast linear shadows that would mimic the normal ridges and valleys that separate the topographic subunits of the nose. Based on the results of nine recent cases, the authors believe the subunit incision is currently the best approach to correcting nasal tip hemangiomas. PMID- 11786788 TI - Hemangiomas of the nasal tip. AB - The treatment of nasal hemangiomas is controversial. Results of nonsurgical treatment methods have been disappointing. In a series of 42 patients with nasal hemangioma, 22 patients underwent early excision. The open rhinoplasty approach proved safe and effective and yielded satisfactory long-term results. The article discusses protocols for evaluation and guidelines for treatment. PMID- 11786789 TI - Facial bone distraction osteogenesis for correction of malocclusion: a more than 70-year-old concept in craniofacial surgery. AB - Bone distraction has been used increasingly since McCarthy and associates showed in their clinical investigation new osseous formation in the elongated area while performing mandibular distraction in 1992. However, at the craniofacial skeletal level, the initial description of the classic technique of distraction osteogenesis should be credited to German craniofacial surgeons Rosenthal (for bone lengthening of the mandible in a microgenia patient around 1927) and Wassmund (for the clinical advancement of a maxilla in a patient with hypoplasia of the upper jaw in 1926). Both procedures are described, and their original schedules and cases are presented. PMID- 11786790 TI - Combined anterolateral thigh flap and vascularized fibula osteoseptocutaneous flap in reconstruction of extensive composite mandibular defects. AB - Extensive composite defects of the oromandibular area are usually created after the surgical treatment of T3 and T4 cancers, requiring complex reconstructive plastic surgical procedures. The preferred treatment method for this type of defect is reconstruction with two free flaps. The use of the vascularized fibula osteoseptocutaneous flap for the bone and inner lining defect is well known and accepted. Among the flaps that can be used for the outer lining and soft-tissue reconstruction, the two most commonly used have been the forearm flap and the rectus abdominis myocutaneous flap. However, these flaps have some disadvantages that restrict their use for this purpose. The forearm flap is usually too thin to cover the fibular bone and reconstruction plate, and the rectus abdominis myocutaneous flap can cause a subclinical reduction in abdominal strength. Both radial forearm and rectus abdominis myocutaneous flaps are difficult to harvest during tumor excision. Because of these drawbacks, over the past several years the authors have preferred to use the anterolateral thigh flap for outer face, neck, and submandibular region reconstructions. From October of 1998 to June of 2000, 22 extensive composite mandibular defect reconstructions using the free anterolateral thigh flap, combined with the vascularized free fibula osteoseptocutaneous flap, were performed at the Chang Gung Memorial Hospital. Complete flap survival was 90.9 percent (40 of 44 flaps). Complete loss was seen in an anterolateral thigh flap, which was then reconstructed with a pectoralis major myocutaneous pedicled flap (2.3 percent). There were five venous problems: three in osteoseptocutaneous free fibula flaps, the other two in anterolateral thigh flaps; all were revised immediately. However, the skin islands of two osteoseptocutaneous free fibula flaps and one anterolateral thigh flap developed partial necrosis (6.8 percent). The other complications were compartment syndrome in the leg in one patient, external carotid artery rupture in one patient, three donor-site infections in two patients, three neck wound infections, and one myocardial insufficiency; all were treated properly. Thirteen patients underwent revision procedures 6 months after the first operation. These procedures included debulking of the flap or revision of the mouth angle or both. Trismus or intraoral contraction was noted in none of these patients. In conclusion, the free anterolateral thigh flap combined with the vascularized fibula osteoseptocutaneous flap seems to be a good choice in the reconstruction of the extensive composite defects of the oromandibular region aesthetically and functionally. PMID- 11786791 TI - Three-dimensional reconstruction of the oral cavity using the free anterolateral thigh flap. AB - Oral cavity reconstruction after removal of locally advanced tumors is particularly difficult because anatomical restoration must accurately reproduce the original structure and enable effective and fast rehabilitation of mastication, swallowing, and phonation. The authors report their 2-year experience with 17 patients surgically treated for oral cavity cancer with reconstruction performed with the free anterolateral thigh flap. Thanks to its thinness and pliability, this flap has proven to be perfectly adaptable to the structural peculiarities of the resected areas and has enabled the authors to considerably reduce the cosmetic and functional complications in the donor area observed with other flaps (such as the radial forearm flap). Flap grafting has always been complete and regular, and no intraoperative and postoperative complications have been observed. Swallowing recovery has always been satisfactory. On the basis of the authors' results, their current approach to oral cavity reconstruction is based on the use of flaps that enable anatomical restoration of the resected areas and reduce morbidity of the donor site. They believe that the anterolateral thigh flap can offer all of these opportunities, and the surgery can be simultaneously performed by two surgical teams. PMID- 11786792 TI - The use of intraoperative autotransfusion during cranial vault remodeling for craniosynostosis. AB - Intraoperative autotransfusion salvages blood shed during surgery for use in immediate resuscitation of the patient. The purpose of this study was to determine whether such autotransfusion decreases the volume of homologous blood transfused in patients undergoing primary cranial vault remodeling for craniosynostosis. The Cobe-Bret 2 autologous blood recovery system (Hemo Concepts, Union, N.J.) was used in 11 cases, and an equal number of consecutive cases did not receive intraoperative autotransfusion. There were no significant differences between the groups with respect to age, sex, and weight. Mean estimated blood loss was 43.2 ml/kg (range, 20.3 to 65.0 ml/kg) in the intraoperative autotransfusion group and 40.2 ml/kg (range, 6.8 to 72.3 ml/kg) in the control group (not statistically significant; p < 0.05). There was no significant difference in volume of homologous blood transfusion between the two groups. The autotransfusion group received 34.1 ml/kg of homologous blood (range, 0 to 60.7 ml/kg), and the control group received a mean of 32.7 ml/kg (range, 14.5 to 60.2 ml/kg). The autotransfusion group received a mean of 10.4 ml/kg of recovered autologous blood (range, 0 to 21.4 ml/kg). In four of the 11 autotransfusion patients, insufficient autologous blood was recovered intraoperatively to warrant transfusion. Results of this study suggest little benefit for the use of intraoperative autotransfusion in primary cranial vault remodeling for craniosynostosis in the young patient. It was hypothesized that this finding was a result of the following: (1) intraoperative autotransfusion blood was usually available only toward the end of the procedure, after homologous blood had already been administered, and (2) the volume of recovered intraoperative autotransfusion blood is minimal, compared with the homologous transfusion volume requirements during an extensive cranial vault remodeling and fronto-orbital advancement procedure. In the context of unproven cost benefit and increasing similar evidence from other comparative studies, emphasis should be directed to other medical and surgical strategies to minimize the need for perioperative blood transfusion. PMID- 11786793 TI - Macromastia: how much of it is fat? AB - A total of 25 patients who underwent bilateral breast reduction were included in this study. Each patient's age, weight, height, and amount of breast tissue removed from each breast were recorded. The body mass index was calculated for each patient. On the day of the operation, tissue samples (two each) were taken from the central, lateral, and preaxillary areas of the breast. One of the samples was weighed, placed in a closed glass container, and heated for 10 minutes in a microwave oven at full power. The liquid fat was separated from the solid residue, and the percentage of fat was calculated. The other sample from each area was examined grossly, and representative sections, corresponding to the distribution of fat and connective tissue, were submitted for evaluation. In these samples, the percentage of fat, gland, and connective tissue was estimated using low-magnification light microscopy. In this group of patients (who had an average age of 34 years and who were significantly overweight as determined by a mean body mass index of 28), it was found (using the microwave method) that there was a mean fat percentage of 61 percent in the central breast area, 74 percent in the lateral breast area, and 73 percent in the preaxillary area. Upon microscopic examination, the pathologist reported that fat accounted for 64 percent of the central breast area, 92 percent of the lateral breast area, and 94 percent of the preaxillary area. On average, the central breast area in macromastia patients had only seven percent gland and 29 percent connective tissue. The lateral and preaxillary areas of the breast had one to three percent gland and five percent connective tissue. The two methods had a significant (p < 0.05) positive correlation in the central breast area, but in the lateral and preaxillary regions, the correlation was poor. In the microscopic examination, there was a tendency to overestimate the amount of fat. Both methods of evaluation used in the study concur that the enlarged breast of macromastia consists primarily of fat and that the glandular element is rather small. PMID- 11786794 TI - A microdissected thin tensor fasciae latae perforator flap. AB - A new method, named "microdissection," has been introduced to create a thin flap by elevating the tensor fasciae latae perforator flap to serve as microdissected thin tensor fasciae latae perforator flap. In microdissection, perforators that run in the posterolateral direction in the adipose tissue after penetrating the deep fascia are dissected meticulously using an operative microscope, and a thin flap is elevated in a single process. The caliber of the perforator artery and vein in the tensor fasciae latae muscle measures approximately 0.7 mm and 0.9 mm, respectively. When transplanting the flap, an end-to-side anastomosis to the main artery measuring 1 to 2 mm is preferable to avoid the risk of arterial thrombosis. In contrast, an end-to-end anastomosis of the perforator vein to the comitans vein of the main artery can be performed safely. In the present study, 11 flaps were transplanted to the sites of skin defects of the neck, hand, axilla, knee, and foot. The author considers that the first clinical indication of this flap is reconstruction of hand skin defects. PMID- 11786796 TI - Contour abnormalities of the abdomen after transverse rectus abdominis muscle flap breast reconstruction: a multifactorial analysis. AB - Contour abnormalities of the abdomen after transverse rectus abdominis muscle (TRAM) flap breast reconstruction occur with all methods of flap elevation and include lower and upper abdominal laxity, epigastric fullness, and hernia. This study is a retrospective analysis of 101 women comparing the many variables that may contribute to an abnormal contour. Statistical analysis comparing the free, pedicled, unilateral, bilateral, muscle-sparing, and non-muscle-sparing flaps was completed using logistic regression. Associated factors, including diabetes mellitus, tobacco use, use of mesh, and prior abdominal operations, were incorporated. Abnormal abdominal contour was present in 13 of 101 women and included 16 specific abnormalities. These included upper abdominal bulge in three women, lower abdominal bulge in eight, and epigastric fullness in five. No woman developed a hernia. Bifactorial analysis demonstrated a significant increase in abnormal contour for the pedicled, bilateral, and non-muscle-sparing TRAM groups when compared with their countervariable groups (free, unilateral, and muscle sparing TRAM, respectively; p < 0.05). Multifactorial analysis demonstrated a significant increase in abnormal contour in two subgroups (p < 0.05). An analysis of associated factors demonstrated a significant increase in abnormal contour for the bilateral TRAM in the presence of a prior lower midline incision (p < 0.05). PMID- 11786798 TI - Contour abnormalities of the abdomen after breast reconstruction with abdominal flaps: the role of muscle preservation. AB - The purpose of the present study was to determine whether contour abnormalities of the abdomen after breast reconstruction with abdominal flaps are related to the harvest of the rectus abdominis muscle. Abdominal contour was analyzed in 155 women who had breast reconstruction with abdominal flaps; 108 women had free transverse rectus abdominis muscle (TRAM) flaps, 37 had pedicled TRAM flaps, and 10 had deep inferior epigastric perforator (DIEP) flaps. The reconstruction was unilateral in 110 women and bilateral in 45 women. Three methods of muscle sparing were used; they are classified as preservation of the lateral muscle, preservation of the medial and lateral muscle, or preservation of the entire muscle. One of these three methods of muscle-sparing was used in 91 women (59 percent) and no muscle-sparing was used in 64 women (41 percent). Postoperative contour abnormalities occurred in 15 woman and included epigastric fullness in five, upper bulge in three, and lower bulge in 10. One woman experienced two abnormalities, one woman experienced three, and no woman developed a hernia. Of these abnormalities, 11 occurred after the free TRAM flap, seven after the pedicled TRAM flap, and none after the DIEP flap. Bilateral reconstruction resulted in 11 abnormalities in nine women, and unilateral reconstruction resulted in seven abnormalities in six women. chi2 analysis of the free and pedicled TRAM flaps demonstrates that muscle-sparing explains the observed differences in upper bulge and upper fullness (p = 0.02), with a trend toward significance for lower bulge (p = 0.06). chi2 analysis of the free TRAM and DIEP flaps does not explain the observed difference in abnormal abdominal contour. Analysis of muscle-sparing and non-muscle-sparing methods demonstrates that the observed difference between the techniques is only explained for a lower bulge after the bilateral free TRAM flap (p = 0.04). PMID- 11786799 TI - Breast reconstruction using tissue expanders and implants in Hodgkin's patients with prior mantle irradiation. AB - Women treated for Hodgkin's disease with mantle irradiation have an increased risk for developing breast cancer. Typically, breast malignancy in Hodgkin's patients presents bilaterally in a younger age group. Skin flap ischemia, poor skin expansion, implant extrusion, capsular contracture, and poor cosmesis are common sequelae of tissue expander/implant breast reconstruction after breast irradiation for failed breast conservation therapy. This has led most surgeons to favor autologous tissue reconstruction in this setting. This study was performed to determine the efficacy of tissue expander/implant breast reconstruction in breast cancer patients who have been treated with prior mantle irradiation for Hodgkin's disease. A retrospective analysis of all breast cancer patients with a history of Hodgkin's disease and mantle irradiation treated with mastectomy and tissue expander/implant reconstruction between 1992 and 1999 was performed. There were seven patients, with a mean age of 35 years (range, 28 to 42 years). The average interval between mantle irradiation and breast cancer diagnosis was 16 years (range, 12 to 23 years). All patients underwent two-stage reconstruction. Textured surface tissue expanders were placed in a complete submuscular position at the time of mastectomy. Expansion was initiated 2 weeks after insertion and continued on a weekly basis until completion. Expanders were replaced with textured surface saline-filled implants as a second stage. Patients were evaluated for skin flap ischemia, infection, quality of skin expansion, implant extrusion, capsular contracture, rippling, symmetry, and final aesthetic outcome. Breast cancer was bilateral in five patients and unilateral in two. Two patients did not undergo simultaneous bilateral breast reconstruction because of metachronous cancer development. One of the patients had an initial transverse rectus abdominis muscle flap breast reconstruction, followed by a tissue expander/implant reconstruction of the opposite breast. The average follow-up was 3 years. Complications were limited to one case of cellulitis after implant placement that resolved with intravenous antibiotics. There were no cases of skin flap ischemia, poor skin expansion, or implant extrusion. Overall patient satisfaction was high and revisions were not requested or required. Symmetry was best achieved with bilateral implants. This study demonstrates the efficacy of tissue expander/implant breast reconstruction in patients treated with prior mantle irradiation. In this series, tissue expansion was reliable with low morbidity. Second-stage placement of permanent implants yielded good aesthetic results without significant capsular contracture. Mantle irradiation did not appear to compromise the prosthetic breast reconstruction. Tissue expander/implant breast reconstruction should remain a viable option in this category of irradiated patients. PMID- 11786800 TI - The effectiveness of muscle flaps for the treatment of prosthetic graft sepsis. AB - The objective of this study was to assess the efficacy and reliability of muscle flaps in the treatment of prosthetic graft sepsis. A retrospective analysis was performed to assess the outcome of all patients with prosthetic graft sepsis who were treated with a muscle flap at Groote Schuur Hospital between January of 1991 and July of 2000. The specific end points studied were flap survival, limb salvage rate, and mortality. A total of 27 muscle flaps were raised to cover 24 sites of graft sepsis in 21 patients. Twenty-five flaps were performed primarily and two secondarily. The mortality rate was zero. Limb salvage was achieved in 15 of 21 patients (71 percent), with no recurrent sepsis after an average follow-up period of 36 months. The groin was the most common site of infection, with an 86 percent incidence. Eighteen sartorius flaps were raised in the groin. Seventeen of the 18 sartorius flaps survived (94 percent), and a 71 percent limb salvage was achieved with no recurrent sepsis after 36 months of follow-up. This series supports the use of muscle flaps for the treatment of prosthetic graft sepsis. The sartorius flap has been shown to be reliable as a flap in the groin, with successful limb salvage in the majority of patients. PMID- 11786802 TI - The reconstructive strategy for improving elbow function in late obstetric brachial plexus palsy. AB - Children with previously untreated obstetric brachial plexus palsy frequently have abnormal elbow function because of motor recovery with aberrant reinnervation, or because of paresis or paralysis. From 1988 to 1997 (9-year period), 62 children with obstetric brachial plexus palsy with resulting elbow deformity underwent various methods of palliative reconstruction to improve elbow function. For motor recovery with aberrant reinnervation, release of aberrantly reinnervated antagonistic muscles and augmentation of paretic muscles form the basis of surgical intervention. The surgical procedures included triceps-to biceps transfer, biceps-to-triceps transfer, brachialis-to-triceps transfer, or combined biceps- and brachialis-to-triceps transfer. Choice of procedures was individualized and randomly determined on the basis of the degree and pattern of aberrant reinnervation between elbow flexors and extensors. In patients' motor recovery with paresis or paralysis, persistently weak elbow flexion was salvaged with a functioning free muscle transplantation or Steindler's flexorplasty, or regional shoulder muscle transfer. In addition, patients with aberrant reinnervation between shoulder abductors and elbow flexors underwent anterior deltoid-to-biceps transfer with a fascia lata graft. All patients had a minimum follow-up of 2 years. Results are assessed and discussed and a reconstructive algorithm is recommended. In general, reconstruction of elbow extension should precede that of elbow flexion. Biceps-to-triceps transfer with preservation of an intact brachialis muscle, or brachialis-to-triceps transfer with preservation of an intact biceps, allows 50 percent of these patients to achieve acceptable elbow flexion and extension in a single-stage procedure. PMID- 11786804 TI - Use of an adipofascial flap based on the proximal perforators of the ulnar artery to correct contracture of elbow burn scars: an anatomic and clinical approach. AB - Different techniques can be used to repair contracture of burn scars on the elbow, including local or distant pedicle flaps, muscle or myocutaneous flaps, free flaps, and tissue expanders. Among these, a pedicled adipofascial flap based on the most proximal two to four perforators of the ulnar artery (located 1 to 5 cm from the origin of the artery) can be anastomosed to form a sort of axially patterned blood supply within the fascia and subcutaneous fat. Therefore, no major vessel in the forearm need ever be severed. In addition, use of this type of flap preserves muscle function. The pedicled adipofascial flap described in this article allows for early rehabilitation because the flap is thin and pliable. Additional advantages are the easy and quick dissection and completion of the procedure in one stage. A detailed anatomic dissection of the flap was performed on 16 upper extremities from fresh cadavers; an injection study was also performed to determine the location and dimensions of the pedicle flap and its area of reach around the elbow. In the past 3 years, 14 flaps were used in 13 patients to repair elbow defects after release of burn scar contractures. Flap dimensions ranged from 4 x 7 cm to 6 x 14 cm (mean flap size, 74 cm). The results were very satisfactory. PMID- 11786805 TI - Peripheral nerve compression associated with low-voltage electrical injury without associated significant cutaneous burn. AB - Although peripheral-nerve injury has been described as clearly related to electrical injury, that electrical injury is usually associated with third- and often fourth-degree burns. The report presented here describes three cases of low voltage electrical injury with associated peripheral-nerve symptoms but without clinically significant cutaneous burns. The symptoms and clinical findings resembled peripheral-nerve compression. The presence of these symptoms and findings in the upper- and lower-extremities and the presence of bilateral involvement suggest a systemic electrical injury that resembles a peripheral neuropathy. Symptoms were relieved by the decompression of nerves at multiple sites in each extremity. Perineurial fibrosis was identified at the time of nerve decompression. It is proposed that the electrical injury causes maximal heat production at areas of minimal limb cross-sectional area. In these areas, the peripheral nerve is in close proximity to bone and fibrous tissue. This results in perineurial fibrosis and symptoms of a compressive peripheral neuropathy. PMID- 11786806 TI - The harvest and clinical application of the superficial peroneal sensory nerve for grafting motor and sensory nerve defects. AB - Potential donor nerves for autografting are finite and usually limited to cutaneous nerves of the extremities. The superficial peroneal nerve is the major lateral branch of the common peroneal nerve that innervates the peroneus longus and brevis muscles and provides sensation to the lateral aspect of the lower leg and the dorsal foot. It has generally been overlooked as a potential donor of nerve autografts. Cadaver dissections were performed on 10 fresh lower extremity specimens to investigate the anatomic characteristics of the superficial peroneal nerve and to refine a harvesting technique for the nerve. Thirty-one patients underwent nerve grafting of 39 upper and lower extremity nerves using the superficial peroneal donor. There were nine median nerves, four ulnar nerves, two radial nerves, two brachial plexus lesions, 16 digital nerves, and six lower extremity nerves grafted. The superficial peroneal nerve provided a consistently long donor, comparable in length to the sural nerve. The anatomic pattern is consistent, the patient positioning is simple, the surgical harvesting technique is straightforward, and the donor defect is acceptable. The superficial peroneal nerve provides a safe and valuable donor nerve, particularly in cases where multiple or very long nerve grafts are required. PMID- 11786807 TI - Limb salvage for soft-tissue malignancies of the foot: an evaluation of free tissue transfer. AB - Free flaps may safely allow meaningful ambulation, durable limb preservation, and better quality of life in patients undergoing resections of soft-tissue cancers of the foot. To prove this, the records of a series of patients at The University of Texas M. D. Anderson Cancer Center (n = 67) who underwent limb salvage following tumor-related resection (n = 71 procedures) from 1989 to 1999 were retrospectively reviewed. Eighteen patients who were not candidates for local flaps or skin grafts received a total of 20 free flaps to preserve their limbs. Most defects (mean size, 78 cm2; range, 20 to 150 cm2) were on a weight-bearing surface of the foot (nine on a weight-bearing heel, three on a plantar foot); the remainder were on a non-weight-bearing surface (six on dorsum, two on a non weight-bearing heel). Melanoma was diagnosed in nine cases (50 percent); soft tissue sarcoma, in seven (39 percent); and squamous cell carcinoma, in two (11 percent). Fasciocutaneous and skin-grafted muscle flaps were used on both weight bearing and non-weight-bearing surfaces. Free-tissue transfer was successful in 17 of 20 cases (85 percent); the three flap losses occurred in two patients. Minor complications (i.e., small hematoma, partial skin graft loss, and delayed wound healing) occurred in five patients. In all cases of successful free-tissue transfer, patients began partial weight bearing at a mean of 7.4 weeks (range, 2 to 12 weeks), and all ultimately achieved full weight bearing. Sixty-seven percent still required special footwear. In one patient, an ulceration on the weight-bearing portion of the flap resolved after a footwear adjustment. Only one patient was lost to follow-up (mean, 23 months). In the 17 remaining patients, limb salvage succeeded in 15 (88 percent). Of these, nine (60 percent) were alive without evidence of disease, three (20 percent) were alive with disease, and three (20 percent) had died of disease. Local recurrence developed in two patients but was successfully treated by excision and closure. No late amputations were required for local control. Thus, it seems that free flaps help facilitate limb salvage and that they may preserve meaningful limb function in patients who undergo resection of soft-tissue malignancies of the foot. PMID- 11786808 TI - Confocal microscopic analysis of scarless repair in the fetal rat: defining the transition. AB - Fetal wounds pass from scarless repair to healing with scar formation during gestation. This transition depends on both the size of the wound and the gestational age of the fetus. This study defines the transition period in the fetal rat model and provides new insight into scarless collagen wound architecture by using confocal microscopy. A total of 16 pregnant Sprague-Dawley rats were operated on. Open full-thickness wounds, 2 mm in diameter, were created on fetal rats at gestational ages 14.5 days (E14; n = 10), 16.5 days (E16; n = 42), and 18.5 days (E18; n = 42) (term = 21.5 days). Wounds were harvested at 24 (n = 18 per gestational age) and 72 hours (n = 24 per gestational age). Skin at identical gestational ages to wound harvest was used for controls. The wounds were fixed and stained with hematoxylin and eosin, antibody to type I collagen, and Sirius red for confocal microscopic evaluation. No E14 rat fetuses survived to wound harvest. Wounds created on E16 fetal rats healed completely and without scarring. E16 fetal rat hair follicle formation and collagen architecture was similar to that of normal, nonwounded skin. Wounds created on E18 fetal rats demonstrated slower healing; only 50 percent were completely healed at 72 hours compared with 100 percent of the E16 fetal rat wounds at 72 hours. Furthermore, the E18 wounds healed with collagen scar formation and without hair follicle formation. Confocal microscopy demonstrated that the collagen fibers were thin and arranged in a wispy pattern in E16 fetal rat wounds and in nonwounded dermis. E18 fetal rat wounds had thickened collagen fibers with large interfiber distances. Two-millimeter excisional E16 fetal rat wounds heal without scar formation and with regeneration of normal dermal and epidermal appendage architecture. E18 fetal rat wounds heal in a pattern similar to that of adult cutaneous wounds, with scar formation and absence of epidermal appendages. Confocal microscopy more clearly defined the dermal architecture in normal skin, scarless wounds, and scars. These data further define the transition period in the fetal rat wound model, which promises to be an effective system for the study of in vivo scarless wound healing. PMID- 11786809 TI - The effects of magnitude and frequency of distraction forces on tissue regeneration in distraction osteogenesis of the mandible. AB - Callus distraction has become an accepted treatment procedure to lengthen hypoplastic mandibles in humans. For this purpose, extraoral and intraoral devices have been applied successfully. The effects of the distraction vector, distractor stability, and rate and frequency of callus distraction on the regenerating tissues have been examined in various studies. In an experimental animal trial on pigs (n = 12), a newly developed microhydraulic osteodistractor was tested. The animals were evenly assigned to two groups to perform a continuous and noncontinuous osteodistraction of the mandible. Initially, the forces necessary to distract the pig mandibles were recorded from a noncontinuous distraction procedure; the results were then used to perform continuous bone distraction. Besides testing the new distractor, the study proved that in continuous osteodistraction, intramembranous bone regeneration occurred, whereas in noncontinuous osteodistraction the bone regeneration process followed a chondroid ossification. In continuous osteodistraction, the bone regeneration proceeded at a higher speed with the lower distraction forces compared with noncontinuous distraction, thereby reducing the consolidation period. Clinical and microscopical results are presented. PMID- 11786810 TI - Mandibular condylar growth alterations after unilateral partial facial paralysis: an experimental study in the rabbit. AB - In a previous study in the rabbit, the authors defined the macroscopic growth alterations after unilateral partial facial paralysis. Dry skull measurements revealed a reduced premaxillary, maxillary, mandibular, and anterior corpus length with a simultaneous increase in mandibular ramal height on the paralyzed side. The authors hypothesize that these mandibular growth alterations are, among others, caused by alterations in condylar growth activity and that an altered occlusal relationship may be involved in the adaptive condylar growth response after facial paralysis.A total of 84 New Zealand White rabbits were used for this study. The animals were randomly assigned to either a control group that was not operated on (n = 28), a group that underwent a sham-operation (n = 28), or an experimental group (n = 28). In the sham-operation group, the facial nerve was dissected as in the experimental group but was left intact. In the experimental group, a left-side partial facial paralysis involving the midfacial muscles was induced by an operation at the age of 12 days. After different follow-up time intervals of 3.5, 7, 14, 21, 28, 42, and 56 days, four control, four sham operation, and four experimental animals (all randomly selected) were killed for histomorphometric measurements of the left control and sham condyles and the left side and right-side experimental condyles. No significant differences between the control and sham-operation groups were found. The other results revealed that shortly after the paralysis in the experimental group, as compared with the controls, a decrease in condylar growth activity was seen before a catch-up increase in activity, as expressed by the time-sequenced decrease and increase in the height of the functional and hypertrophic chondroblast layer. The response on the right side was analogous, though less intense. It is suggested that the mandibular ramal growth alterations might be the result of a chain of adaptations involving the lateral pterygoid muscle and the condylar growth activity. The unilaterally restricted length increment of the maxillary snout, as a result of the loss of tensile forces caused by paralysis of the midfacial musculature, necessitated an adaptation in the position of the mandible to maintain a normal occlusal relationship. Subsequently, the function of muscles involved or influenced by an altered mandibular position, such as the lateral pterygoid muscle, were changed. These altered muscle activities induced condylar growth adaptations, which in turn explained the alterations in mandibular ramal growth. PMID- 11786811 TI - Prefabrication of bone by use of a vascularized periosteal flap and bone morphogenetic protein. AB - The purpose of this pilot study was to prefabricate a vascularized bone graft by using a vascularized periosteal flap containing osteoprogenitor cells, a structural matrix, and recombinant human bone morphogenetic protein-2 (rhBMP-2). In a rat model, a periosteal flap vascularized by the saphenous artery and vein was dissected off the medial surface of the tibia. This flap consisted of three layers-periosteum, muscle, and fascia-and was tubed on itself to form a watertight chamber that was then transferred on its vascular pedicle to the groin. A total of 78 vascularized periosteal chambers were constructed in 39 animals and divided into 10 groups. In group 1, the periosteal chamber was left empty. Groups 2, 3, and 4 consisted of the periosteal flap and rhBMP-2, but in group 3, the proximal vascular pedicle was ligated, and in group 4, the flap was harvested without the periosteal layer and turned inside out. Groups 5 through 10 consisted of the vascularized periosteal flap containing several different structural matrices (calcium alginate spheres, polylactic acid, or demineralized bone matrix) with or without rhBMP-2. Animals were killed at 2, 4, or 8 weeks in each group. The presence and density of any new bone formation was evaluated both radiologically and histologically. Significant bone formation was seen only in those periosteal flaps containing rhBMP-2 and either the calcium alginate or polylactic acid matrix. New bone formation increased both radiologically and histologically from 2 weeks to 8 weeks only in the periosteal flaps containing the polylactic acid matrix and rhBMP-2. This preliminary study therefore suggests that four factors-blood supply, osteoprogenitor cells in the periosteal layer, a biodegradable matrix, and rhBMP-2-are required for optimal prefabrication of a vascularized bone graft. PMID- 11786812 TI - Myogenic differentiation by human processed lipoaspirate cells. AB - The use of undifferentiated cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. For such strategies to succeed, a readily available source of myogenic precursor cells must be identified. We have previously shown that cells isolated from raw human lipoaspirates, called processed lipoaspirate cells, display multilineage mesodermal potential in vitro. Because human liposuctioned fat is available in large quantities and can be harvested with low morbidity, it may be an ideal source of stem cells for tissue-engineering applications. In this study, processed lipoaspirate cells were isolated from raw lipoaspirates harvested from eight patients who underwent cosmetic surgery. Processed lipoaspirate cells were placed in promyogenic conditions for up to 6 weeks, and the expression of the myogenic markers MyoD1 and myosin heavy chain was confirmed by using structure, histology, and reverse transcriptase-polymerase chain reaction. Histologic results were quantitated as an indicator or myogenic differentiation levels. We found that induced human processed lipoaspirate cells form multinucleated cells after 3 weeks of induction, indicative of the formation of myotubes. In addition, MyoD1 and skeletal muscle myosin heavy chain are expressed at distinct time points during differentiation with MyoD1 expression preceding expression of myosin. Finally, approximately 15 percent of human processed lipoaspirate cells can be induced toward myogenic differentiation 6 weeks after induction. In summary, our findings suggest that human processed lipoaspirate cells differentiate into myogenic cells. Furthermore, these cells may be a useful source for skeletal muscle engineering and repair. PMID- 11786814 TI - The effect of two episodes of denervation and reinnervation on skeletal muscle contractile function. AB - Sensory or motor "baby-sitting" has been proposed as a clinical strategy to preserve muscle integrity if motion-specific axons must regenerate over a long distance to reach denervated target muscles. Denervated muscles are innervated temporarily by using axons from nearby sensory or motor nerves. After motion specific motor axons have reached the target, the baby-sitter nerve is severed and motion-specific axons are directed to the target. Although this strategy minimizes denervation time, the requisite second episode of denervation and reinnervation might be deleterious to muscle contractile function. This study was designed to test the hypothesis that two sequential episodes of skeletal muscle denervation and reinnervation result in greater force and power deficits than a single peripheral nerve injury and repair. Adult Lewis rats underwent either transection and epineurial repair or sham exposure of the left peroneal nerve. After a 4-month recovery period, the contractile properties of the extensor digitorum longus muscle of the sham exposure group (control, n = 9) and one of the nerve division and repair groups (repair group 1, n = 9) were evaluated with measurements of the maximum tetanic isometric force, peak power, and maximal sustained power. A third group of rats underwent a second cycle of nerve division and repair (repair group 2, n = 9) at this same time point. Four months postoperatively, contractile properties of the extensor digitorum longus muscles were evaluated. Maximum tetanic isometric force and peak power were significantly reduced in repair group 2 rats as compared with repair group 1 and control rats. Maximal sustained power was not significantly different between the groups. These data support our working hypothesis that skeletal muscle contractile function is adversely affected by two cycles of denervation and reinnervation as compared with a single episode of nerve division and repair. PMID- 11786815 TI - Differing flow patterns between ischemically challenged flap skin and flap skeletal muscle: implications for salvage regimens. AB - In this study, the authors tested the hypothesis that there is a significant difference in spatial patterns of reflow in skin as opposed to skeletal muscle after an ischemic insult. The authors believe that this pathophysiologic difference between the two flap types has significant implications for flap salvage strategies. Bilateral buttock skin flaps (10 x 18 cm) and latissimus dorsi myocutaneous flaps (10 x 20 cm) were elevated in Landrace pigs (n = 7). Flaps on one side of the animal were randomly assigned to 6 hours of arterial occlusion, with the contralateral side acting as control. At 15 minutes, 1 hour, and 4 hours after reflow, radioactive microspheres (15 microm) were injected into the left ventricle. After 18 hours of reperfusion, skin and muscle viability were estimated by intravenous fluorescein and soaking in nitroblue tetrazolium, respectively. Flow rates in the skin with an ischemia-reperfusion injury were significantly reduced (30 to 53 percent), at all time intervals, compared with controls. The flow rate in the fluorescent skin with ischemia-reperfusion injury of the latissimus dorsi flaps (0.037 ml/min/g at 15 min) was greater than in that of the buttock flaps (0.018 ml/min/g). The muscle flaps with ischemia-reperfusion injury had significantly higher flow rates than control muscle flaps at all time intervals studied (at 1 hour, 0.32 ml/min/g compared with 0.16 ml/min/g, respectively). In flap skeletal muscle, an early hyperemic phase during reperfusion maintains a significant blood flow to all regions, including the area of the flap that is destined for necrosis. In flap skin, however, there is a marked decrease in flow rates. These differences have important implications for the intravascular delivery of therapeutic agents to the damaged portions of the flap. Transdermal drug delivery systems should be explored as an alternative to intravascular regimens for the salvage of flap skin with ischemia-reperfusion injury. PMID- 11786816 TI - Evaluation of performance characteristics of the medicinal leech (Hirudo medicinalis) for the treatment of venous congestion. AB - Medicinal leeches (Hirudo medicinalis) are a standard treatment for venous congestion, a complication that can occur after reconstructive surgery. If the cause of venous congestion cannot be surgically corrected, then medicinal leeches are used to temporarily increase perfusion levels and maintain physiologic requirements within the congested tissue. Leeches increase perfusion within congested tissue by actively drawing off blood as a bloodmeal. Furthermore, the leech bite continues to bleed and relieve congestion after detachment because of the anticoagulation effects of leech saliva left behind in the bite. In a porcine model, a 10 x 10 cm cutaneous flank flap was congested by clamping the venae comitantes. Four medicinal leeches were allowed to attach to the congested flap, and parameters of active feeding and passive bleeding after detachment were recorded. The average bloodmeal volume for the medicinal leeches was 2.45 ml. Average passive bleeding for the first 2 and 4 hours after leech detachment totaled 2.21 and 2.50 ml, respectively, with 90 percent of passive bleeding occurring within 5 hours after detachment. Laser Doppler imaging indicated that the spatial arrangement of surface perfusion increases were localized to a 1.6-cm diameter circle around the leech head (bite) and corresponded well with the visual return of normal skin tones to the same area. This study provides a realistic and quantitative estimate of the spatial and volumetric characteristics of leech feeding and passive bleeding using a clinically relevant model of acute, severe congestion. PMID- 11786817 TI - Lower lip reconstruction with tongue flap in paramedian bilateral congenital sinuses. PMID- 11786818 TI - Autosomal dominant inheritance pattern for trigger thumb. PMID- 11786820 TI - Frontalis sling operation with deep temporal fascial graft in blepharoptosis repair. PMID- 11786821 TI - The iliolumbar artery as the nutrient pedicle for an iliac crest graft: a new technique in reconstruction of the lumbar spine. PMID- 11786822 TI - Functional osteomuscular free-tissue transfer: the reinnervated fibula-flexor hallucis longus free flap. PMID- 11786823 TI - Teaching technical skills: training on a simple, inexpensive, and portable model. AB - The purpose of this study was to determine whether surgical residents could significantly improve their performance on a specific surgical procedure after a brief practice session with feedback. Attending plastic surgeons, using valid and reliable checklists and global rating scales, objectively assessed 37 junior surgical residents while performing two-flap Z-plasties on pig thighs (one before and one after a one-on-one, 5-minute practice session with feedback). The total cost per resident was $1.00 (Canadian currency). After the practice session, total checklist scores improved from 7.3 (range, 1 to 9) to 7.9 (range, 5 to 9), and the total global rating scores improved from 29.1 (range, 13 to 41) to 31.9 (range, 19 to 43). Paired Student's t tests revealed significant improvement in both the mean total checklist scores (p < 0.05) and mean total global rating scores (p < 0.01). Also, the global rating score for appearance and quality of the final surgical product significantly improved from 2.7 to 3.3 after the practice session (p < 0.01). There were no significant differences in performance scores between men and women, between first-year and second-year residents, with residents' previous experience with the Z-plasty procedure, or with resident's base surgical specialties. The results of this prospective study indicate that training on a simple and portable model with very brief individualized practice and feedback is an effective and inexpensive way of improving resident performance. A 5-minute practice session with a surgical trainee before performing a procedure on a living patient may significantly improve the patient's surgical performance and produce a superior result. PMID- 11786824 TI - Surgical reconstruction of pediatric pressure sores: long-term outcome. AB - The long-term outcome after the surgical repair of pressure sores in the adult population has been well studied. Recurrence rates from 25 to 80 percent have been reported, despite improvements in surgical repair and mechanical support devices. Such high recurrence rates have led many investigators to question the rationale for the surgical closure of pressure sores. There are no published long term data that document pressure sore recurrence after surgical treatment in the pediatric population. A retrospective analysis of all patients who underwent surgical reconstruction of grade III and IV pressure sores at the Children's Hospital of Philadelphia from 1987 to 1999 was performed. During this 12-year period, 19 consecutive patients with a mean age of 16.2 years were operated on for 25 pressure sores. Follow-up was obtained for 15 patients (79 percent), who underwent repair for 20 pressure sores. Mean postoperative follow-up was 5.3 years (range, 11 months to 11 years). Mean age at the time of surgery was 16.5 years. The overall pressure sore recurrence rate was 5 percent (1 of 20 sores). Overall patient recurrence (previous patient who developed a new sore) was 20 percent (3 of 15 patients). In contrast to the recurrence rates reported for the surgical repair of pressure sores in the adult population, the recurrence rate of 5 percent in the pediatric population is significantly lower. This demonstrates that the surgical reconstruction of pressure sores in the pediatric patient can be successful and provide long-term skin integrity. PMID- 11786825 TI - A New Year's resolution and resolve: we must remember. PMID- 11786826 TI - Achieving a predictable 24-hour return to normal activities after breast augmentation: part I. Refining practices by using motion and time study principles. AB - The purpose of this study was to develop techniques to predictably return patients receiving inframammary and axillary, subpectoral breast augmentation to full normal activities within 24 hours of their primary breast augmentation. This 5-year study applies motion and time study principles to refine practices in augmentation mammaplasty to reduce perioperative morbidity and shorten patient recovery. Retrospective data for operative times, medications administered, recovery times, times to discharge, and time to return to normal activities were collected from patient chart reviews and patient contacts from 1982 to 1984 (group 1, n = 16, axillary partial retropectoral augmentations) and 1990 (group 2, n = 16, inframammary partial retropectoral augmentations). Videotapes from operative procedures of groups 1 and 2 were analyzed with macromotion and micromotion study principles, and tables of events were formulated for all operating room personnel, detailing every step of each function they performed. The events tables were then refined into detailed scripts by using motion and time study principles. Scripts were used for surgeon and personnel training and for reference during operative procedures. Extensive changes in all aspects of patient care, including patient education, preparation, operative planning, implant selection, anesthesia techniques, surgical techniques, instrumentation, and postoperative care derived from data and videotape studies of patients in groups 1 and 2 were then applied to a third group of patients (group 3), collecting prospective data over a 3-year period (1998 to 2000). Group 3 (n = 627) data included timed events, medications, and time to return to normal activities. Patients in group 3 had substantially shorter anesthesia, operation, and postanesthesia care unit times and time to discharge and time to return to normal activities compared with groups 1 and 2. Of the patients in group 3, 96 percent were able to return to normal activities, lift their arms above their heads, lift normal-weight objects, and drive their car without any narcotic medications, drains, bandages, special bras, or other adjunctive treatments within 24 hours after their partial retropectoral breast augmentation. Applying motion and time study principles to analysis and refinement of surgeon and personnel actions and surgical techniques resulted in a substantial reduction in perioperative morbidity and a simpler, shorter 24-hour return to normal activities without intercostal blocks, narcotic pain medications, drains, bandages, or other adjunctive devices in 96 percent of 627 augmentation patients. PMID- 11786828 TI - Achieving a predictable 24-hour return to normal activities after breast augmentation: Part II. Patient preparation, refined surgical techniques, and instrumentation. AB - The goal of this study was to develop practices that would allow patients undergoing subpectoral augmentation to predictably return to full normal activities within 24 hours after the operation, free of postoperative adjuncts. Part I of this study used motion and time study principles to reduce operative times, medication dosages, perioperative morbidity, and recovery times in augmentation mammaplasty. Part II of the study focuses on details of patient education, preoperative planning, instrumentation, and surgical technique modifications that were identified, modified, and implemented to achieve the results reported in part I. Two groups of 16 patients each (groups 1 and 2) were studied retrospectively for comparison to a third group of 627 patients (group 3) studied prospectively. Patients in group 1 had axillary partial retropectoral breast augmentations in 1982-1983, using dissociative anesthesia, blunt instrument implant pocket dissection, and Dow Corning, double-lumen implants containing 20 mg of methylprednisolone and 20 cc of saline in the outer lumen of the implants. Patients in group 2 (1990) had inframammary, retromammary augmentations by using a combination of blunt and electrocautery dissection, Surgitek Replicon polyurethane-covered, silicone gel-filled implants, and general endotracheal anesthesia. Patients in group 3 (1998 to 2001, n = 627) had inframammary partial retropectoral, inframammary retromammary, and axillary partial retropectoral augmentations under general endotracheal anesthesia. Refined practices and surgical techniques from studies of groups 1 and 2 were applied in group 3. Videotapes from operative procedures of groups 1 and 2 were analyzed with macromotion and micromotion study principles, and tables of events were formulated for each move during the operation for all personnel in the operating room. Extensive details of surgical technique were examined and reexamined in 13 different stages by using principles of motion and time studies described in part I of this study to maximize efficiency without any change in quality. Unnecessary or unproductive motions and techniques were progressively eliminated, and essential, productive techniques were streamlined to eliminate wasted time and motion. Instrumentation and surgical techniques were evaluated in detail and modified to minimize bleeding and tissue trauma. Detailed data were presented in part I of this study that document shorter operative times, recovery times, time to discharge home, and time to return to normal activities. This part focuses on the patient education, preoperative planning, instrumentation, and surgical technique changes that were implemented on the basis of the findings in part I of the study. More extensive patient information integrated with staged informed consent resulted in a more informed and confident patient. Applying motion and time study principles to analysis and refinement of instrumentation and surgical techniques resulted in a substantial reduction in perioperative morbidity and a simpler, shorter 24-hour return to full normal activity for 96 percent of the patients undergoing breast augmentation in group 3 compared with groups 1 and 2. More than 96 percent of patients in group 3 were able to return to normal activities, lift their arms above their heads, lift normal-weight objects, and drive their car within 24 hours after their partial retropectoral breast augmentation. Patient education, preoperative planning, instrumentation, and surgical technique modifications based on motion and time study video analyses reduced surgical trauma and bleeding, reduced perioperative morbidity, and allowed 96 percent of 627 breast augmentation patients in group 3 a predictable return to full, normal activity in 24 hours or less. Specific surgical factors that contributed to these results included (1) prospective hemostasis techniques with a zero tolerance for even the smallest amount of bleeding, (2) strict "no-touch" techniques for periosteum and perichondrium, (3) eliminating all blunt dissection, (4) performing all dissection under direct vision, (5) modified and simplified instrumentation, and (6) optimal use of muscle relaxants during subpectoral dissection. PMID- 11786830 TI - Prevention and treatment of side effects and complications of cutaneous laser resurfacing. PMID- 11786832 TI - Lip augmentation with superficial musculoaponeurotic system grafts: report of 103 cases. AB - Many patients suitable for a lip augmentation are of face lift age, and could benefit from a simultaneous lip enhancement during the rhytidectomy procedure. The healthy, live superficial musculoaponeurotic system (SMAS) tissue obtained from the face lift can be recycled and grafted with minimal additional operating time. From April of 1995 to January of 2000, 103 patients (99 women and four men) underwent a lip augmentation procedure by the senior author (N.L.) using SMAS grafts harvested from a simultaneous rhytidectomy. Indications for surgery were purely aesthetic in all 103 cases. The surgical technique used for the SMAS graft lip augmentation is as follows: Using a narrow tenotomy scissors, an intramuscular tunnel was created with blunt and sharp dissection across the lip. The graft, obtained from the posterior edge of the SMAS dissection, is left as long as possible, and is pulled through the tunnel with a tendon forceps. The lips are then stretched manually from the central point upward and downward, respectively. It is important to avoid suturing the ends of the graft into the closure; the grafts should be allowed to move freely, to avoid postoperative tethering on smiling or mouth opening. Most patients expressed some initial concern with their early appearances caused mainly by the swelling. By 2 weeks, most patients were extremely pleased with the size and shape, and their main concern was that the lip fullness would shrink even more. By 3 to 4 weeks, shrinkage largely ceased and the correction remained for varying periods, some as long as 5 years. A sampling of the results was obtained by means of a questionnaire mailed to all patients having undergone the SMAS graft lip augmentation. Fifty-four patients (52 percent) returned the questionnaire with their responses. Of those who responded to the survey, 42 patients (78 percent) reported fuller lips than before their operation. Significantly, 11 of 14 patients (79 percent) followed up after 24 months postoperatively reported fuller lips and excellent or good results. Complications and unsatisfactory results were very rare, occurring generally at the beginning of the learning curve of the series.SMAS grafts are useful for long-lasting lip augmentation, producing a youthful appearance by adding natural, soft roundness and fullness to lips without the artificial look and feel of synthetic material. PMID- 11786834 TI - Three-dimensional endoscopic midface enhancement: a personal quest for the ideal cheek rejuvenation. AB - Standard face-lift techniques are excellent for the treatment of the jawline and neck. Treatment of the area between the lower eyelid and the corner of the mouth required the development of techniques in the intermediate lamella of the face. Alternative techniques of subperiosteal dissection by means of lower eyelid incisions were described with good aesthetic results but at the expense of increased morbidity and complications. All these techniques were also two dimensional manipulations of the soft tissues of the face. The author presents a different approach that he believes is close to the ideal in terms of safety, morbidity, and complications. Although midface rejuvenation may be performed alone, it is more commonly done as a component of total facial rejuvenation. The midface is approached by means of a combination of a temporal slit incision and an upper oral sulcus incision; no eyelid access is used. Fifty percent of the midface dissection is performed under direct visualization, and 50 percent is performed under endoscopic control. Dissection of the temporal area is done under the temporoparietal fascia down to the zygomatic arch. The anterior two-thirds of the zygomatic arch periosteum is elevated along with a few millimeters of the intermediate temporal fascia and the fascia of the masseter muscle. The subperiosteal dissection of the zygoma and maxilla is completed with the medial extension of the dissection just medial to the infraorbital nerve. The orbital fat pads are released by means of intraoral route, and the lateral and middle fat pads are advanced over the orbital rim and fixed to the masseter tendon and the periosteum of the maxillary shelf at the intraoral incision. Three suspension points are typically used on the midface, each one with a different action. All are anchored to the temporal fascia proper. The vascularized Bichat's fat pad is mobilized and fixed with 4-0 polydioxanone sutures. This provides a volumetric cheek augmentation and improvement of the jowl. The inferior malar periosteum and fascia is used for malar imbrication with 4-0 polydioxanone sutures. This provides an anterior projection of the cheek and elevates the corner of the mouth. The suborbicularis oculi fat is used for en bloc vertical suspension of the cheek. This also improves the infraorbital V deformity. This technique has been used in close to 200 patients over the last 5 years. The complications have been minimal: two cases of temporary paresis of the levator of the upper lip, one case of paresis of the orbicularis oris (unilateral), one case of buccinator muscle dysfunction, and two moderate infections that were treated with simple drainage. The degree of facial edema has been minimal compared with the open or the transblepharoplasty approach. Typically, patients can return to work 2 weeks after surgery.The three-dimensional endoscopic midface enhancement provides a technique of midface remodeling that provides the missing dimension (volume) to the rejuvenation of the midface. This can be done with a minimal rate of complications, and the aesthetic results surpass by far the results of other midface techniques previously described by the author. PMID- 11786840 TI - A surgical solution to the deep nasolabial fold. PMID- 11786838 TI - Planning elective operations on patients who smoke: survey of North American plastic surgeons. AB - Patient smoking status affects many aspects of plastic surgery, including patient selection, counseling, management, and outcomes. No specific recommendations for performing elective procedures on patients who smoke are available. The goal of this study was to determine the current practice standards and attitudes toward this often controversial topic. In September of 2000, 1600 members of the American Society for Aesthetic Plastic Surgery were sent questionnaires, 955 of which were returned. Questions elicited categorical answers, either dichotomous or multiple choice. Data were evaluated using logistic regression and the chi square and binomial tests. Our results show that 60 percent (p < 0.01) of plastic surgeons routinely perform a less than optimal procedure on their patients who smoke. The survey measured willingness to perform various operative procedures on patients who smoke and types of smoking cessation aids offered. Of those physicians who require patients to quit smoking before surgery, only 16.7 percent (p < 0.01) would perform a nicotine test if they suspected noncompliance. Interestingly, 28.6 percent (p < 0.01) of the physicians responding admit to a smoking history, whereas only 1.5 percent (p < 0.01) continue to smoke, compared with the national smoking rate of almost 25 percent. Physicians who are previous smokers are less likely to offer smoking cessation aids than those who have never smoked, and the proportion not offering aids increases as the amount of previous smoking increases (p = 0.02). This study shows that a wide range of opinions exists on which elective surgical procedures should be performed on patients who smoke. Furthermore, the physician's prior smoking history influences this decision. No clear consensus exists on how best to treat patients who smoke who request elective surgeries. Although surgeons would prefer to operate on nonsmokers, they are faced with a significant population of patients who use tobacco. No clear consensus exists on how best to treat these individuals. Advancements in wound healing research and smoking cessation aids will provide more insight into this treatment dilemma. PMID- 11786842 TI - An investigation of changes in body image following cosmetic surgery. PMID- 11786844 TI - Beyond competence. PMID- 11786845 TI - Ten years ago. PMID- 11786846 TI - Breast cancer and augmentation mammaplasty: the preoperative consultation. PMID- 11786849 TI - Intralesional OK-432 injection therapy for ganglia. PMID- 11786850 TI - Pregnancy in the early period after abdominoplasty. PMID- 11786851 TI - Choosing size for an augmentation mammaplasty. PMID- 11786852 TI - Rules relating to the administration of anesthesia. PMID- 11786853 TI - The nasolabial flap for nasal lining defects. PMID- 11786854 TI - Lower eyelid cysts following transconjunctival blepharoplasty. PMID- 11786855 TI - Unilateral galactocele in a male infant. PMID- 11786856 TI - The versatility of the pudendal thigh fasciocutaneous flap used as an island flap. PMID- 11786857 TI - Construction of an innervated whole toe by separating the expanded neighboring toe. PMID- 11786858 TI - Oberlin's ulnar nerve transfer to the biceps nerve in Erb's birth palsy. PMID- 11786859 TI - Can operating room tables be made safer and more comfortable? PMID- 11786860 TI - A simple method for urethra reconstruction with a full-thickness skin graft. PMID- 11786861 TI - Otoplasty and skin excision. PMID- 11786862 TI - Auricular displacement with rhytidectomy. PMID- 11786863 TI - AAO coordinates specialties to recruit and retain dental faculty. PMID- 11786864 TI - Orthodontic graduate education survey, 1983-2000. AB - Throughout academic year 1999/2000, the fourth in a series of national surveys sponsored by the American Association of Orthodontists Council on Education was conducted to determine the status of graduate education, to assemble information on the didactic and clinical material being taught, and to provide a basis for comparison with past and future studies. The results of the previous studies were published in 1984, 1989, and 1995. The specific purpose of the 2000 study was to identify trends and evaluate new developments in orthodontic education over the past 17 years. A 346-item survey questionnaire, covering 8 major areas of orthodontic graduate education, was sent to graduate program directors in the United States and Canada. The major areas analyzed were program organization, graduate students, faculty, facilities, clinical details, treatment techniques, research, and curriculum. Findings showed that curricular time devoted to clinical activities is increasing, but curricular time devoted to research is declining. The rate of student publications is down precipitously. The numbers of full-time and half-time faculty members are declining, and departments increasingly rely on part-time faculty to meet teaching needs. Overall experience levels of the faculty are declining. Fewer faculty members are American Board of Orthodontics diplomates. Faculty salaries, when adjusted for inflation, are down from 1994. Tuitions have increased dramatically over the last 5 years. Approximately 50% of all programs are now 3 years long. Clinic fees are now roughly two thirds those of local private-practice fees. Students are treating more mixed dentition and craniofacial cases and fewer nonsurgical adult cases. Fewer departments are relying on centralized radiographic facilities in their parent dental schools, preferring in-department radiography. Approximately 50% of the first-year students are female. PMID- 11786865 TI - Effectiveness of early treatment of Class II malocclusion. AB - The purpose of this study was to examine and report the effectiveness of early treatment with the headgear/biteplate and the bionator in patients with Class II malocclusion regardless of the mechanism of correction and to compare early treatment results with changes over a similar time period in an observation group. The role of factors such as compliance was examined to determine their contribution to effective treatment. The experimental design was a prospective, longitudinal, randomized controlled trial. At the end of the early-treatment period, all 3 groups differed significantly (overall, P = .001) in percentage of treatment goal achieved, with median values of 83% for the bionator group, 100% for the headgear group, and 14% for the observation group. In both treated and observation subjects, the percentages of goal achieved varied by initial molar class severity (treated, P =.0205; observation, P = .0040) and race (treated, P = .0314; observation, P = .0416). Significant correlations in the treated subjects were identified between percentage of goal achieved and bone age (13 bones) (r = 0.16; P = .037), bone age (20 bones) (r = 0.16; P = .043), compliance (r = 0.26; P = .0005), and initial overjet (r = -0.26; P = .0095). Significant correlations were not detected in the observation group. Sex, treatment group, age, mandibular plane angle, pretreatment, and retention did not significantly affect percentage of goal achieved among the treated and the observation subjects. Correlation between normalized compliance scores and percentage of goal achieved was high for both bionator (r = 0.50) and headgear subjects (r = 0.49) at the end of treatment. Multivariate analysis suggested that headgear may be superior to bionator/biteplane in achieving a Class II correction during early treatment. PMID- 11786866 TI - When planning to use an implant for anchorage, how long do you have to wait to apply force after implant placement? PMID- 11786867 TI - A 3-dimensional analysis of molar movement during headgear treatment. AB - Superimposition of serial cephalograms provides a limited description of tooth movement that could be complemented by data obtained from serial dental casts. The aim of this study was to develop a mathematical method for superimposing 3 dimensional data obtained from selected landmarks on longitudinally collected dental casts to describe maxillary first molar movement during headgear treatment. The material consisted of dental casts taken bimonthly from 36 children whose Class II Division 1 malocclusion was treated with straight-pull headgear during a 24-month period. Control data were collected from initial and final models of 38 subjects with a similar malocclusion who were not treated during a 24-month observation period. Spatial data from each subject's initial model were oriented similarly in an anatomically derived coordinate system, and a best-fit superimposition of palatal rugae landmarks from subsequent models allowed the measurement of molar movement. On average, headgear treatment resulted in distal movement of the molars, and the fitted net difference between treated and control subjects was 3.00 mm (SE, 0.37 mm; P < .001). Also, the headgear caused significantly more molar extrusion (0.56 mm; SE, 0.20 mm; P < .006) and buccal expansion (0.58 mm; SE, 0.17 mm; P < .001) on average than in the control group. Poor reliability of the method for measuring molar rotations indicated that they could not be determined accurately. Longitudinal description of molar movement for each subject revealed great individual variability in the amount and pattern of tooth movement. Several reasons could account for the wide range of individual variation and warrant exploration. PMID- 11786869 TI - Efficiency of early and late Class II Division 1 treatment. AB - The aim of this study was to assess the efficiency of early and late Class II Division 1 treatment in the mixed and permanent dentition. Treatment efficiency was defined as a better result in a shorter treatment time. We examined 204 patients with Class II Division 1 malocclusions treated in the early mixed dentition (n = 54), late mixed dentition (n = 104), and permanent dentition (n = 46). The pretreatment and posttreatment dental casts were evaluated with the peer assessment rating (PAR) index. The duration of treatment decreased with progressing dental development: patients in the early mixed dentition (dental stage [DS] 2) were treated for 57 months, patients in the late mixed dentition (DS 3) for 33 months, and patients in the permanent dentition (DS 4) for 21 months. Patients treated exclusively with fixed appliances had a shorter treatment duration (19 months for Herbst and 24 months for multibracket) than did patients treated with functional appliances or a combination of appliances (38 months for functional appliances and 49 months for a combination). The PAR score reduction (improvement) increased with progressing dental development: DS 2 patients had a PAR score reduction of 64%, DS 3 patients had a reduction of 73%, and DS 4 patients had a reduction of 77%. Patients treated exclusively with fixed appliances had a greater PAR score reduction (77%) than did patients treated with functional appliances or a combination (60% for fixed appliances and 71% for functional or a combination). Based on the results of this investigation, we concluded that treatment of Class II Division 1 malocclusions is more efficient in the permanent dentition (late treatment) than it is in the mixed dentition (early treatment). PMID- 11786870 TI - Orthodontic correction of transverse arch asymmetries. AB - The purpose of this study was to determine whether asymmetries in the transverse dimension are corrected after orthodontic treatment and to determine differences between age-group responses in the correction of transverse asymmetries. Sixty orthodontically treated subjects with transverse asymmetries in arch width were grouped by age, treatment modality, and arch location. Casts were analyzed to assess the correction of arch asymmetry. Lateral cephalometric analysis was performed to assess vertical change differences between age groups, and to detect correlations between vertical and arch-width changes. After orthodontic treatment, it was found that the arch width between the 2 halves of the arch still showed significant differences (P < .05); it was also found that arch-width changes between pretreatment and posttreatment showed significant differences (P < .05) for nonextraction treatment and for the anterior region in extraction treatment. Analysis of lateral cephalograms showed significant differences (P < .05) in vertical-dimension changes between growing and nongrowing subjects. The Pearson product moment correlation test showed no significant correlation at the P < .05 level between vertical and arch-width changes. We concluded that, for this sample, asymmetry in transverse dimension was not corrected, and there was no difference between growing and nongrowing individual responses in transverse asymmetry correction. PMID- 11786871 TI - Relationship between formation/eruption of maxillary teeth and skeletal pattern of maxilla. AB - Previous reports have indicated that formation and eruption of the maxillary teeth, especially the molars, are delayed in skeletal Class III patients compared with Class I and Class II patients. However, the relationship between the formation/eruption of maxillary teeth and the skeletal pattern of the maxilla is not yet clear. To examine this relationship, we studied 81 skeletal Class III Japanese patients (mean age, 8.8 years). The sample was divided into 2 groups: a maxillary retrusion (MR) group, characterized by a small SNA angle and a short palatal length, and a control group in which those values were in the normal range for patients of Japanese descent. There was no significant difference in the rate of formation for the maxillary and mandibular teeth between the 2 groups. The eruption of the maxillary second molars was delayed in the MR group compared with the control group. There were no significant differences between the 2 groups for any other teeth. A multiple-regression analysis was carried out to examine whether the skeletal pattern of the maxilla is a useful indicator for predicting the eruption of the maxillary teeth. The results showed that palatal length and chronologic age were significant independent (explanatory) variables for predicting eruption of the maxillary second molars. These findings indicated that the skeletal pattern of the maxilla is a useful indicator for predicting the timing of maxillary molar eruption when considering treatment of skeletal Class III malocclusions. PMID- 11786872 TI - Malposition of unerupted mandibular second premolar associated with agenesis of its antimere. AB - Aberrant tooth positions--such as infraocclusion, mesially ectopic maxillary first molar, palatally displaced canine, tooth transposition, and tooth rotation- are gaining attention as variables in a putative, genetically related pattern of dental anomalies. This study, using panoramic roentgenograms, was undertaken to measure the angular position of the unerupted mandibular second premolar (MnP2) in children. The experimental subjects were 17 children with an unerupted MnP2 and agenesis of the other MnP2, a likely indicator of site-specific genetic disturbance. An age/sex-matched control-reference group was similarly measured for comparison. The hypothesis tested was that the unerupted, developing MnP2 teeth in the experimental subjects would show measurably greater malpositions than those of the control sample. The results indicated a 10 degrees increase in distoangular inclination for the unerupted MnP2 in the agenesis sample; this was a highly significant difference statistically (P = .003), compared with the MnP2 inclinations in the control sample. These findings, associating exaggerated distoangular malposition of the unerupted MnP2 in children with agenesis of the contralateral MnP2, identify a new phenotype of dental developmental disturbance to add to the accumulated evidence supporting shared genetic mechanisms for dental anomaly patterns. PMID- 11786873 TI - Soft tissue profile in Anatolian Turkish adults: Part I. Evaluation of horizontal lip position using different soft tissue analyses. AB - This study investigated cephalometrically the horizontal lip position of Anatolian Turkish adults using the soft tissue analyses of Steiner, Ricketts, Burstone, Sushner, Holdaway, and Merrifield. Ninety-six adults (55 females, mean age, 21.63 years; 41 males, mean age, 22.45 years) with Angle Class I occlusal relationships were selected from the dentistry students at the University of Istanbul and called the dentally normal group. Their lateral cephalometric radiographs were analyzed, and 44 subjects (21 females, mean age, 21.35 years; 23 males, mean age, 21.41 years) with normal anteroposterior (ANB angle, 2 degrees +/- 2 degrees ) and vertical (SN-MP angle, 32 degrees +/- 5 degrees ) skeletal relationships were selected from the dentally normal group and called the dentally and skeletally normal group. Ten linear and 6 angular measurements were analyzed on each radiograph, and the significance of the differences between the groups was studied by means of the Mann-Whitney U test. The results of this study indicate that in Anatolian Turkish adults (1) the upper and lower lips were retrusive according to the norms of Steiner and Ricketts; (2) both the upper and lower lip values were within the normal range according to Burstone's B line; (3) the upper lip was protrusive and the lower lip was retrusive compared with the norms developed by Sushner for a black population; (4) the value for the lower lip was similar to the standard proposed by Holdaway, while the values for the nasal prominence and the H angle were greater than Holdaway's norms; and (5) the Z angle was smaller than the norm established by Merrifield. PMID- 11786874 TI - Soft tissue profile in Anatolian Turkish adults: Part II. Comparison of different soft tissue analyses in the evaluation of beauty. AB - This study examined the soft tissue analyses of Steiner, Ricketts, Burstone, Sushner, Holdaway, and Merrifield to evaluate orthodontists' perceptions of Anatolian Turkish adults' beauty. Forty-four subjects (21 females, mean age, 21.35 years; 23 males, mean age, 21.41 years) with Angle Class I occlusal relationship, and normal anteroposterior (ANB angle, 2 degrees +/- 2 degrees ) and vertical (SN-MP angle, 32 degrees +/- 5 degrees ) skeletal relationships were selected from the dental students at the University of Istanbul. The material consisted of lateral cephalometric radiographs and facial-profile slides of these subjects. Ten linear and 6 angular measurements were analyzed on each radiograph, and the facial profiles were judged as poor, fair, good, or excellent by 6 raters. After the scoring, 34 subjects (16 females and 18 males) were placed in the unattractive group, and 10 subjects (5 females and 5 males) were placed in the attractive group. The significance of the differences between the groups was studied by means of the Mann-Whitney U test. The results demonstrated that persons having a high mandibular plane angle, a small nose, protrusive lips, and a retrusive profile were selected as attractive. Among the 7 esthetic lines used to evaluate the soft tissue profile, only Ricketts' norms for upper and lower lips corresponded to the values we found for attractive profiles. PMID- 11786875 TI - Validated numerical modeling of the effects of combined orthodontic and orthognathic surgical treatment on TMJ loads and muscle forces. AB - Investigations of the changes in the mechanics of the craniomandibular system as a result of treatment have been limited by the lack of validated models of this system. The aims of this project were to (1) validate numerical model predictions of temporomandibular joint (TMJ) eminence morphology and muscle forces produced during molar biting and (2) use the validated models to calculate the changes in TMJ and muscle forces as a consequence of treatment involving orthognathic surgery. Ten volunteers participated; their combined orthodontic and orthognathic surgical treatments were completed. Three-dimensional anatomical data from each subject were used in computer models to predict the sagittal TMJ eminence morphology and joint and muscle forces for each subject, consistent with the neuromuscular objectives of minimizing joint loads and muscle effort. The actual shape of the eminence in each subject was measured with jaw tracking. Surface electromyographic recordings were a measure of the muscle forces involved in static molar biting. Model predictions were compared with measured data from the subjects for eminence shape (R(2) = 0.96) and for muscle activity ratios (R(2) = 0.98). The strength of these relationships validated the models for use in calculating changes in joint loads and muscle forces after treatment. The results suggested that the mechanics of the masticatory system are affected by the combined treatments. The TMJ loads increased in 8 subjects. The average increases in condylar and muscle forces were 4% relative to the applied bite force, but in 1 case the increases were up to 20%. Therefore, although average increases in the forces were small, some persons may experience biologically significant increases in joint and muscle forces as a result of treatment. PMID- 11786876 TI - Craniofacial features of patients with Class III abnormalities: growth-related changes and effects of short-term and long-term chincup therapy. AB - The craniofacial features of patients with Class III abnormalities, including growth-related changes and effects of short-term and long-term chincup therapy, were studied. Twenty female subjects were treated with chincups and an orthopedic force of 500 g for 31 months (short-term treatment group). Another 36 female patients were treated with chincups and a force of 250 to 300 g for 86 months (long-term treatment group). All subjects treated with chincups had lateral cephalograms taken before treatment (T0), after treatment (T1), and at retention (T2). Cross-sectional lateral films of 562 skeletal Class III girls were selected from the records of 1265 Class III patients at a public hospital and private clinics as controls. The controls were selected to approximately match the ANB angle, Wits appraisal, and chronological age of the treated groups. Short-term treatment resulted in a slight improvement in ANB angle and Wits appraisal, while long-term treatment resulted in a significant improvement in ANB angle and Wits appraisal. Such treatment also resulted in a significant inhibition of the growth of the ramus (2.2 mm) and body length (3.6 mm) of the mandible, a backward rotation of the mandible, and a reduction (8.2 degrees ) of the gonial angle. However, there was no alteration of any parameter of the maxilla and the cranial base, except the length of S-N and N-S-Ar in the long-term treatment group. Subjects who completed the long-term treatment protocol retained the changes by wearing the appliance during sleep, with a force of 200 g applied to the center of the chin. PMID- 11786877 TI - Orthodontics justified as a profession. PMID- 11786879 TI - Recommended reading? PMID- 11786878 TI - Estimating the human health risk from possible BSE infection of the British sheep flock. AB - Following the controversial failure of a recent study and the small numbers of animals yet screened for infection, it remains uncertain whether bovine spongiform encephalopathy (BSE) was transmitted to sheep in the past via feed supplements and whether it is still present. Well grounded mathematical and statistical models are therefore essential to integrate the limited and disparate data, to explore uncertainty, and to define data-collection priorities. We analysed the implications of different scenarios of BSE spread in sheep for relative human exposure levels and variant Creutzfeldt-Jakob disease (vCJD) incidence. Here we show that, if BSE entered the sheep population and a degree of transmission occurred, then ongoing public health risks from ovine BSE are likely to be greater than those from cattle, but that any such risk could be reduced by up to 90% through additional restrictions on sheep products entering the food supply. Extending the analysis to consider absolute risk, we estimate the 95% confidence interval for future vCJD mortality to be 50 to 50,000 human deaths considering exposure to bovine BSE alone, with the upper bound increasing to 150,000 once we include exposure from the worst-case ovine BSE scenario examined. PMID- 11786880 TI - Aging alters the apoptotic response to genotoxic stress. PMID- 11786881 TI - Further concern over rules that impede research. PMID- 11786882 TI - Future of neuroprotective drugs in doubt. PMID- 11786883 TI - Faculty demands AIDS drugs for all. PMID- 11786884 TI - . . . and at the CDC. PMID- 11786885 TI - Plans to step up bioterrorism research via the NIH. PMID- 11786886 TI - New NCI director appointed. PMID- 11786887 TI - Anthrax exceptionalism? PMID- 11786888 TI - Government center to offer genomics expertise. PMID- 11786889 TI - 'Biopiracy' issue stops research. PMID- 11786891 TI - Anthony Fauci. PMID- 11786894 TI - The microarray way to tailored cancer treatment. PMID- 11786895 TI - Integrin indecision. PMID- 11786896 TI - Pten-uating neural growth. PMID- 11786897 TI - When the KChIPs are down. PMID- 11786898 TI - Shedding growth factors in cardiac hypertrophy. PMID- 11786899 TI - Tumor-specific mutations in p53: the acid test. PMID- 11786901 TI - ADHD and addiction. PMID- 11786903 TI - Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. AB - Inhibition of alphavbeta3 or alphavbeta5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Here we report that mice lacking beta3 integrins or both beta3 and beta5 integrins not only support tumorigenesis, but have enhanced tumor growth as well. Moreover, the tumors in these integrin deficient mice display enhanced angiogenesis, strongly suggesting that neither beta3 nor beta5 integrins are essential for neovascularization. We also observed that angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF) are augmented significantly in the absence of beta3 integrins. We found no evidence that the expression or functions of other integrins were altered as a consequence of the beta3 deficiency, but we did observe elevated levels of VEGF receptor-2 (also called Flk-1) in beta3-null endothelial cells. These data indicate that alphavbeta3 and alphavbeta5 integrins are not essential for vascular development or pathological angiogenesis and highlight the need for further evaluation of the mechanisms of action of alphav-integrin antagonists in anti-angiogenic therapeutics. PMID- 11786904 TI - Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. AB - G-protein-coupled receptor (GPCR) agonists are well-known inducers of cardiac hypertrophy. We found that the shedding of heparin-binding epidermal growth factor (HB-EGF) resulting from metalloproteinase activation and subsequent transactivation of the epidermal growth factor receptor occurred when cardiomyocytes were stimulated by GPCR agonists, leading to cardiac hypertrophy. A new inhibitor of HB-EGF shedding, KB-R7785, blocked this signaling. We cloned a disintegrin and metalloprotease 12 (ADAM12) as a specific enzyme to shed HB-EGF in the heart and found that dominant-negative expression of ADAM12 abrogated this signaling. KB-R7785 bound directly to ADAM12, suggesting that inhibition of ADAM12 blocked the shedding of HB-EGF. In mice with cardiac hypertrophy, KB-R7785 inhibited the shedding of HB-EGF and attenuated hypertrophic changes. These data suggest that shedding of HB-EGF by ADAM12 plays an important role in cardiac hypertrophy, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy. PMID- 11786905 TI - Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells. AB - In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Gram-positive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein-coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin-binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4. PMID- 11786906 TI - Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection. AB - To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4+ T cells. Polyclonal peripheral blood CD4+ cells were costimulated ex vivo and subjects were given infusions of up to 3 x 1010 activated CD4+ cells. Dose-dependent increases in CD4+ cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4+CCR5+ cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4+Ki-67+ cells increased whereas CD4+ T cells containing T cell-receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection. PMID- 11786907 TI - Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. AB - Respiratory syncytial virus (RSV) is a major cause of morbidity from respiratory infection in infants, young children and the elderly. No effective vaccine against RSV is currently available and studies of the natural history of RSV infection suggest repeated infections with antigenically related virus strains are common throughout an individual's lifetime. We have studied the CD8+ T-cell response during experimental murine RSV infection and found that RSV inhibits the expression of effector activity by activated RSV-specific CD8+ T cells infiltrating the lung parenchyma and the development of pulmonary CD8+ T-cell memory by interfering with TCR-mediated signaling. These data suggest a possible mechanism to explain the limited duration of protective immunity in RSV infection. PMID- 11786908 TI - Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils. AB - Death domain-containing receptors of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family can induce apoptosis upon activation in many cellular systems. We show here that a conserved phosphotyrosine-containing motif within the death domain of these receptors can mediate inhibitory functions. The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), SHP-2 and SH2 containing inositol phosphatase (SHIP) bound to this motif in a caspase independent but cell-dependent manner. We also found that stimulation of death receptors disrupted anti-apoptosis pathways initiated (at least under certain conditions) by survival factors in neutrophils. In these cells, activation of the tyrosine kinase Lyn, an important anti-apoptotic event, was prevented as a consequence of death-receptor stimulation, most likely through association of the receptor with activated SHP-1. Thus, we provide molecular and functional evidence for negative signaling by death receptors. PMID- 11786909 TI - Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. AB - Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention. PMID- 11786910 TI - Interleukin-6-deficient mice develop mature-onset obesity. AB - The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement. The obese Il6-/- mice had disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment. To investigate the possible mechanism and site of action of the anti-obesity effect of IL-6, we injected rats centrally and peripherally with IL-6 at low doses. Intracerebroventricular, but not intraperitoneal IL-6 treatment increased energy expenditure. In conclusion, centrally acting IL-6 exerts anti-obesity effects in rodents. PMID- 11786911 TI - Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity. AB - Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinical utility is limited by toxicity. The development of less toxic, liposomal formulations of cisplatin has been hampered by the low water solubility and low lipophilicity of cisplatin, resulting in very low encapsulation efficiencies. We describe a novel method allowing the efficient encapsulation of cisplatin in a lipid formulation; it is based on repeated freezing and thawing of a concentrated solution of cisplatin in the presence of negatively charged phospholipids. The method is unique in that it generates nanocapsules, which are small aggregates of cisplatin covered by a single lipid bilayer. The nanocapsules have an unprecedented drug-to-lipid ratio and an in vitro cytotoxicity up to 1000 fold higher than the free drug. Analysis of the mechanism of nanocapsule formation suggests that the method may be generalized to other drugs showing low water solubility and lipophilicity. PMID- 11786915 TI - Crystal structure of the endosomal SNARE complex reveals common structural principles of all SNAREs. AB - SNARE proteins are crucial for intracellular membrane fusion in all eukaryotes. These proteins assemble into tight complexes that connect membranes and may induce fusion. The crystal structure of the neuronal core complex is represented by an unusually long bundle of four alpha-helices connected by 16 layers of mostly hydrophobic amino acids. Here we report the 1.9 A resolution crystal structure of an endosomal SNARE core complex containing four SNAREs: syntaxin 7, syntaxin 8, vti1b and endobrevin/VAMP-8. Despite limited sequence homology, the helix alignment and the layer structure of the endosomal complex are remarkably similar to those of the neuronal complex. However, subtle variations are evident that characterize different SNARE subfamilies. We conclude that the structure of the SNARE core complex is an evolutionarily conserved hallmark of all SNARE complexes and is intimately associated with the general role of SNAREs in membrane fusion. PMID- 11786916 TI - Hydrophobic core packing in the SH3 domain folding transition state. AB - How tightly packed is the hydrophobic core of a folding transition state structure? We have addressed this question by characterizing the effects on folding kinetics of > 40 substitutions of both large and small amino acids in the hydrophobic core of the Fyn SH3 domain. Our results show that residues at three positions, which we designate as the 'core folding nucleus', are tightly packed in the transition state, and substitutions at these positions cause the largest changes in the folding rate. The other six positions examined appear to be loosely packed; thus, substitutions at these positions with larger hydrophobic residues generally accelerate folding, presumably by increasing the rate of nonspecific hydrophobic collapse. Surprisingly, the folding rate can be greatly accelerated by residues that also significantly destabilize the native state structure. Furthermore, mutants with identical thermodynamic stability can differ by up to 55-fold in their folding rates. These results highlight the importance of hydrophobic core composition, as opposed to only topology, in determining the folding rate of a protein. They also provide a new explanation for the 'abnormal' phi-values observed in many protein folding kinetics studies. PMID- 11786917 TI - SNARE assembly and disassembly exhibit a pronounced hysteresis. AB - SNARE proteins are essential for intracellular membrane fusion of eukaryotes. Their assembly into stable four-helix bundles bridges membranes and may provide the energy for initiating membrane fusion. In vitro, assembly of soluble SNARE fragments is accompanied by major structural rearrangements that can be described as a folding reaction. The pathways and the thermodynamics of SNARE protein interactions, however, are not known. Here we report that assembly and dissociation of two distantly related SNARE complexes exhibit a marked hysteresis. The assembled and disassembled native states are separated by a kinetic barrier and cannot equilibrate on biologically relevant timescales. We suggest that the hysteresis is a hallmark of all SNARE complexes and that complex assembly and disassembly follow different pathways that may be independently controlled. PMID- 11786918 TI - Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway. AB - WNT signaling pathway is implicated in embryogenesis as well as in carcinogenesis. We have previously cloned and characterized Frizzled-1 (FZD1), FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, and FZD10, encoding seven-transmembrane type WNT receptors. Here, expression of FZD10 mRNA in various types of human cancer and effects of FZD10 mRNA microinjection into Xenopus early embryos were investigated. Northern blot analyses revealed relatively high-level expression of 4.0-kb FZD10 mRNA in cervical cancer cell lines HeLa S3, SKG-I, SKG-IIIa, and in a glioblastoma cell line A-172. Matched tumor/normal expression array analysis revealed significant up-regulation of FZD10 mRNA in 2 cases of primary colon cancer. Function of FZD10 was next investigated by using Xenopus axis duplication assay, in which positive regulators of the WNT - beta-catenin - TCF signaling pathway induce axis duplication. Injection of wild-type FZD10 mRNA into the ventral marginal zone of 4-cell-stage Xenopus embryos induced partial axis duplication in 40% of embryos. Ventral injection of Thr579Ala FZD10 mRNA or Val581Leu FZD10 mRNA with mutations in the C-terminal Ser/Thr-X-Val motif also induced partial axis duplication in about 40% of embryos. Furthermore, ventral injection of FZD10 mRNA significantly augmented the potential of co-injected Xenopus wnt-8 (Xwnt-8) mRNA to induce complete axis duplication. These results suggest that up-regulation of FZD10 mRNA in several types of human cells might lead to carcinogenesis through activation of the beta-catenin - TCF signaling pathway synergistically with some class of WNTs. PMID- 11786919 TI - Prevention of development of N,N'-dimethylhydrazine-induced colon tumors by a water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia in male ICR mice. AB - The protective effects of a dietary water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi or Mannentake) mycelia (designated as MAK) against development of colon tumors were investigated in male ICR mice. The animals were given weekly injections of N,N'-dimethylhydrazine (DMH, 10 mg/kg body weight) for the initial 10 weeks to induce colon carcinogenesis, and then fed on diet with or without 5% MAK for 10 weeks. There were no significant differences in incidence and the total number of colon tumors between the groups. However, the MAK diet group demonstrated significantly reduced sizes of tumors in comparison with the MF diet group. Moreover, this was linked to a lowered PCNA positive index and shortening of the germinal region in the colon. beta-catenin positive tumor cell nuclei were also significantly decreased in the MAK group. The present results thus indicate that dietary MAK could act as a potent chemopreventive agent for colon carcinogenesis. PMID- 11786920 TI - Adrenomedullin and its receptors are expressed in the zona glomerulosa of human adrenal gland: evidence that ADM enhances proliferation and decreases apoptosis in cultured ZG cells. AB - Adrenomedullin (ADM) is a hypotensive peptide, that derives from the proteolytic cleavage of pro(p)ADM and acts through two subtypes of receptors, called L1 receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR may function as a calcitonin gene-related peptide or a selective ADM receptor depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of proteins, named receptor-activity-modifying protein (RAMPs). Reverse transcription (RT) polymerase chain reaction (PCR) consistently allowed the detection of pADM mRNA in zona glomerulosa (ZG), but not zona fasciculata-reticularis (ZF/R) cells of eight human adrenal cortexes. Despite the rather high level of pADM mRNA, immunocytochemistry and radioimmunoassay showed that the expression of ADM as protein in the ZG was weak. However, ZG cells expressed peptidyl-glycine alpha amidating monooxigenase, the enzyme converting immature ADM to the mature peptide, thereby suggesting their potential ability to produce active ADM. RT-PCR demonstrated the presence in ZG, but not ZF/R cells of the specific mRNAs of L1 R, CRLR and RAMPs1-3. Semiquantitative PCR showed that L1-R expression was higher than that of CRLR, while the level of expression of the three RAMPs was nearly the same. ADM (10(-8) M) inhibited both angiotensin-II (10(-9) M)- and K(+) (10( 2) M)-stimulated aldosterone secretion from cultured ZG cells, without affecting basal production. ADM (10(-8) M) also increased proliferative activity and lowered apoptotic deletion of cultured cells. All the effect of ADM were reversed by the ADM-receptor antagonist ADM(22-52). In conclusion our study provides evidence that i) human ZG cells express ADM and ADM receptors of both L1 and CRLR/PAMP2,3 subtypes; and ii) through the activation of these receptors, ADM exerts an aldosterone antisecretagogue action and a growth promoting effect on cultured ZG cells, the latter an effect which includes both stimulation of proliferation and inhibition of apoptosis. Taken together, these findings make it likely that endogenous ADM system plays a potentially important role in the paracrine/ autocrine regulation of human adrenal cortex. PMID- 11786921 TI - A severe connatal form of Pelizaeus Merzbacher disease in a Czech boy caused by a novel mutation (725C>A, Ala242Glu) at the 'jimpy(msd) codon' in the PLP gene. AB - Pelizaeus Merzbacher disease (PMD) is an X-linked recessive disorder of the central nervous system myelination caused by mutations involving the proteolipid protein gene (PLP). Early nystagmus and developmental delay, progressive pyramidal, cerebellar and dystonic signs as well as white matter changes in brain MRI are typical for PMD. The PLP gene can be affected by two major types of mutations. A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD. The PLP protein is a higly conserved across species and is identical in human, mouse and rat. We describe a 13-year-old Czech boy with an early and severe developmental delay. His maternal uncle died at the age of one year and was also early and severely psychomotoricly retarded. The patient was the first child of healthy unrelated parents born after an uneventful pregnancy and delivery in 1988. Hyperbilirubinemia and bronchopneumonia and early stridor complicated his neonatal period. Diffuse hypotonia, nystagmus, psychomotor retardation, visual and hearing impairment have been observed in the patient since the age of 6 weeks. White matter abnormalities, cortical and periventricular atrophy were detected by MRI at the age of 6 and 11 years, respectively. Despite these signs and results an accurate clinical diagnosis was unclear until the age of 11 years. Last neurological examination in 1999 showed no nystagmus anymore, but extremely dystrophic limbs, truncal deformation, due to severe scoliosis, tetraplegia with hyperreflexia in C5C7 and areflexia L2S2 and positive pyramidal signs. The boy had no visual or speech contact. DNA tests followed the clinical suspicion for PMD. At first, duplication of PLP gene was excluded by quantitative comparative PCR. Direct sequencing of PLP gene detected a novel mutation in exon 6, a missense mutation 725C-->A (Ala242Glu) in the patient and in his mother and later also in his maternal grandmother. The same codon, but to valine (Ala242Val) is mutated in jimpy(msd) mouse, which is the frequently used animal model for PMD. Prenatal diagnosis for the next pregnancy has been offered to the family. The patient died recently at the age of 13 years due to respiratory failure. Our results support the data on the importance of this conserved amino acid alanine at codon 242. PMID- 11786922 TI - Molecular bases for the anti-parasitic effect of NO (Review). AB - Nitric oxide (NO) has emerged as an important cytotoxic and cytostatic effector for a number of pathogens, including viruses, bacteria, fungi, and parasites. When the microbicidal effect of NO occurs, the NO-mediated S-nitrosylation of cysteine containing proteins (e.g., cysteine proteases) appears to be a common and widespread mechanism. This overview concerns parasitic cysteine proteases as NO targets, providing molecular bases for the parasiticidal effect of NO. PMID- 11786923 TI - Molecular cloning and characterization of mouse Wnt14b, clustered with mouse Wnt3 in mouse chromosome 11. AB - WNTs are a family of secreted-type glycoproteins implicated in embryogenesis and carcinogenesis. We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15. WNT14B gene is clustered with WNT3 gene in human chromosome 17q21, and mRNA expression of WNT14B is significantly up-regulated by retinoic acid during the early phase of neuronal differentiation in human NT2 cells. Here, we identified mouse Wnt14b gene fragments in mouse genome draft sequence AL596108.5 by using bioinformatics, and isolated mouse Wnt14b cDNAs by using cDNA-PCR. Mouse Wnt14b was found to encode a 359-amino-acid WNT family protein with the N terminal signal peptide, an N-linked glycosylation site, and 24 conserved cysteine residues. Mouse Wnt14b showed 92.5% total-amino-acid identity with human WNT14B, and 64.2% total-amino-acid identity with human WNT14. Mouse Wnt14b gene, consisting of 4 exons, was clustered with mouse Wnt3 gene in mouse chromosome 11. Mouse Wnt14b mRNA was relatively highly expressed in 17-day embryo, and also expressed in adult brain, kidney, liver, 7-day embryo, and 11-day embryo. This is the first report on molecular cloning and characterization of mouse Wnt14b. PMID- 11786924 TI - Identification of genes coding enzymes for ascomycin tetra-hydropyranose ring formation. AB - Macrocyclic polyketides have generated great interest in biosynthetic chemistry because of the structural complexity and medicinal activities. The synthetic genes consist of the number and type of active sites of modular polyketide synthases. The cosmid library - prepared with the ascomycin (an antibiotics with immunosuppressive activity) - producer, Streptomyces sp. AA6554 genome was screened with an ascomycin ketosynthase gene probe, and one and a half modules were isolated. Database analysis shows that one of the modules consists of the genes coding a series of enzymes for the tetra-hydropyranose ring synthesis. PMID- 11786925 TI - Regulation of alkaline phosphatase promoter activity by forkhead transcription factor FKHR. AB - Alkaline phosphatase (ALP) is a basic marker of osteoblast maturation and osteogenesis. However, the mechanisms of the ALP gene regulation in osteoblasts remain elusive. In this study, we examined the expression of forkhead transcription factor FKHR, a regulator of hepatic glucose metabolic and proapoptotic genes, in osteogenic cells and the effect of FKHR on transcription of the ALP gene. RT-PCR and immunoblot analyses revealed the expression of FKHR in osteogenic MC3T3-E1, SaOS2, and UMR 106 cells. Reporter assays demonstrated that the overexpression of FKHR stimulated ALP promoter activity through the forkhead response element in its promoter. These results suggest that ALP is a target gene regulated by FKHR and that FKHR contributes to osteoblast maturation and osteogenesis. PMID- 11786926 TI - Molecular cloning and characterization of human SOX17. AB - SOX proteins are a family of transcription factors with high-mobility-group DNA binding domain (HMG box) homologous to SRY, which are implicated in embryogenesis. Xenopus Sox17 alpha, Sox17 beta, and Sox3 are reported to negatively modulate the WNT - beta-catenin - TCF signaling pathway. Here, human SOX17 gene fragments were identified in human genome draft sequences by using bioinformatics, and SOX17 cDNAs were isolated by using cDNA-PCR. Human SOX17 was found to encode a 414-amino-acid protein with a HMG box, which was homologous to SOX18 and SOX7. SOX17 gene, consisting of 2 exons, was located in human chromosome 8q12-q13 region. SOX17 mRNAs of 2.5- and 2.2-kb in size were detected in adult heart, lung, spleen, testis, ovary, placenta, fetal lung, and kidney. In normal gastrointestinal tract, SOX17 mRNA was preferentially expressed in esophagus, stomach and small intestine than in colon and rectum. SOX17 mRNA was almost undetectable in human cancer cell lines HL-60, HeLa S3, K-562, MOLT-4, Raji, SW480, A549, G-361, and also in 66 cases of human primary tumors derived from various tissues, except one case of primary cervical cancer. This is the first report on molecular cloning and characterization of human SOX17. PMID- 11786927 TI - Effects of D-mannoheptulose upon D-glucose metabolism in pancreatic B and non-B islet cells. AB - D-mannoheptulose was recently proposed to be transported into cells mainly at the intervention of GLUT2. In the present study, the heptose (10 mM) decreased the steady state content of dispersed rat pancreatic islet cells in D-[U (14)C]glucose, and inhibited to a greater relative extent the utilization of D-[5 (3)H]glucose, the oxidation of D-[U-(14)C]-glucose and its conversion to radioactive amino acid when the dispersed islet cells were incubated at 16.7 mM rather than 2.8 mM D-glucose. A comparable situation was found in purified islet B-cells, whereas D-mannoheptulose only exerted minor to negligible effects upon the metabolism of D-glucose in non-B islet cells. This coincided with a much higher uptake of D-[(3)H]mannoheptulose by B, as distinct from non-B, islet cells. These findings indicate that the unexpectedly greater relative inhibitory action of D-mannoheptulose upon D-glucose metabolism by isolated islets (or dispersed islet cells) observed at high rather than low hexose concentration cannot be accounted for solely by differences in the relative contribution of non B cells to total D-glucose metabolism by islets incubated at increasing concentrations of D-glucose. A comparable metabolic response to D-mannoheptulose is indeed observed in purified B cells. It could be attributable, in part at least, to D-glucose and D-mannoheptulose countertransport, resulting inter alia in a greater net uptake of the heptose by B cells exposed to a high concentration of the hexose. PMID- 11786928 TI - Effects of cytochalasin B and D upon insulin release and pancreatic islet cell metabolism. AB - Cytochalasin B is known to enhance insulin release evoked by nutrient and non nutrient secretagogues, including D-glucose, despite inhibiting D-glucose uptake and metabolism in pancreatic islets. In the present study, cytochalasin D, which failed to affect D-glucose uptake and metabolism by isolated islets, also augmented glucose-stimulated insulin release, but unexpectedly to a lesser extent than cytochalasin B. Such was not the case, however, in islets stimulated by non glucidic nutrients such as 2-ketoisocaproate or the association of L-leucine and L-glutamine. This situation coincided with the fact that cytochalasin B inhibited more severely D-glucose metabolism in non-B, as distinct from B, islet cells and, in the former case, caused a relatively greater inhibition of hexose catabolism at 2.8 mM than at 16.7 mM D-glucose. Nevertheless, even in the presence of forskolin, cytochalasin B was more efficient than cytochalasin D in augmenting glucose-stimulated insulin secretion. Thus, although these data document that non B islet cells are more sensitive than purified islet B cells to cytochalasin B, at least in terms of inhibition of D-glucose catabolism, such a difference and its possible consequence upon the release of glucagon and other non-insulinic hormones by non-B islet cells do not appear sufficient to account for the greater enhancing action of cytochalasin B, as distinct from cytochalasin D, upon glucose stimulated insulin output. Likewise, the latter difference does not appear attributable to a greater efficiency of cytochalasin B, as compared to cytochalasin D, upon the mechanical events involved in nutrient-stimulated exocytosis of insulin granules. Hence, the present findings suggest a so-far unidentified interference of cytochalasin B with the B-cell glucose-sensing device. PMID- 11786929 TI - Short-term oral administration of a product derived from a probiotic, Clostridium butyricum induced no pathological effects in rats. AB - Recent studies have suggested that short chain fatty acids (SCFAs) exert a therapeutic effect on some human and experimental animal diseases. In a previous study, we showed that Clostridium butyricum produces high levels of SCFAs in the culture system used. In addition, an additive based on yogurt was effective in eliminating and masking the odor derived from SCFAs in the product. The aim of the present study was to investigate the effects for oral administration of the product, which was derived from Clostridium butyricum and contains a high level of SCFAs, in rats. Male and female Wistar Hannover GALAS rats, 5 weeks old, were allowed a mixture of the standard diet plus the product derived from Clostridium butyricum (50% w/w) with 0.1% additive for 17 days (n=6). The control rats were also allowed a standard diet plus tap water (50% w/w) with 0.1% additive (n=6). After 17 days, a laparotomy was performed. A hemocyte count, and biochemical and electrolyte analyses were subsequently carried out. The esophagus, stomach, small intestine, cecum and large intestine were investigated macroscopically and microscopically. Results showed that the rats grew normally for the duration of the experimental period. In particular, the body weights of the product-fed male rats were significantly increased as compared to those of the control-fed male rats. There were no significant differences in the organic weight between the product-fed and control-fed rats, except for a significantly increased weight of the small intestine in the product-fed female rats. No pathological abnormalities were found in the hemocyte count, the biochemical and electrolyte analyses, or the macroscopic and microscopic findings. It is possible that this novel product with the additive exerts therapeutic effects on some gastrointestinal disorders. PMID- 11786930 TI - The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (review). AB - The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but surprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained. PMID- 11786931 TI - Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis. AB - Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD. PMID- 11786932 TI - Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction. AB - Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer. PMID- 11786933 TI - [Polymethylmethacrylate (PMMA) in anterior cervical spine surgery - current situation in Germany]. AB - In German speaking countries Polymethylmethacrylate (PMMA) is widely used as spacer material after ventral microdiscectomy of the cervical spine. With the introduction of other materials i.e. titanium, carbon and polyetheretherketone (PEEK) and upcoming reports about long term complications PMMA is currently in discussion. We present the results of an enquiry about the use of PMMA and the complications observed in Germany. - 100 German neurosurgical departments perform annually 8608 anterior cervical discectomies and fusions, 3410 (40%) with PMMA, 2373 (27%) with titanium, 2370 (27%) with bone graft, 407 (5%) with carbon and 48 (1%) without fusion materials. In 47 of the 100 departments PMMA is used on regular base, in 18 occasionally and in 35 never. The use of PMMA is limited to a single cervical segment in 12 departments, 21 are using PMMA in two and 22 in more than two segments. - Fracturing of fusion material was observed in PMMA in 13 cases (0.15% per year), in bone grafts in 33 (0.53% per year) and in carboncages in one case (0.05% per year). Dislocations of PMMA is reported in 66 cases (0.7% per year), of bone grafts in 32 (0.73% per year), of titanium spacers in 20 (0.37% per year) and of carboncages in 4 cases (0.33% per year). - In conclusion PMMA is still the most widely used spacer material after anterior cervical discectomy in Germany. An increased complication rate in comparison with other implants could not be observed. PMID- 11786934 TI - [Background and first results about methodological characteristics of the Aachen Life Quality Inventory]. AB - Health-related quality of life has become an important criterion for assessing disease impact and treatment outcome. Therefore, we developed a questionnaire called Aachen Life Quality Inventory (ALQI) for the use in neurosurgical patients with brain damage. The ALQI is derived from the German version of the Sickness Impact Profile (SIP). The 117 items are formulated on a concrete behavioral level covering the following dimensions of health-related quality of life: 1. activation; 2. mobility; 3. house-work; 4. social contact; 5. family relations; 6. ambulation; 7. work; 8. free-time activities; 9. autonomy; 10. communication; 11. cognitive capacity. As in the SIP, a summary score of total impairment (ALQI Total score), a summary score covering the psycho-social dimension (ALQI Psycho social score) and a summary score covering aspects of physical functioning (ALQI Physical score) can be calculated. The ALQI consists of a self-rating and a parallel proxy-rating version. The ALQI was validated and psychometrically verified using the data of as yet 231 neurosurgical patients with brain damage of mixed etiology (subarachnoid hemorrhage, closed-head injury, benign brain tumors). Internal consistency (Cronbach's Alpha) ranged from.68 to.91 for the subscales, while it was.97 for the whole instrument,.94 for the psycho-social and.93 for the physical score. The internal consistency for the subscales of the proxy-rating version of the ALQI ranged between.77 and.92, while it was.97 for the whole inventory and.94 for the psycho-social and the physical scores, respectively. Examination of construct validity revealed substantial correlations with a wide range of relevant neurological, neurosurgical and neuropsychological parameters. Beyond other findings, substantial associations emerged with several neuropsychological tests (r =.30 to r =.50), the Glasgow Outcome Scale (r =.39; p <.00) and in patients after subarachnoid hemorrhage with the Hunt& Hess grading (r =.28; p <.001). According to these results, the ALQI promises to become a valid and reliable means for assessing quality of life in patients with brain damage. Nevertheless, further analyses using larger patient samples and with particular emphasis on the investigation of the retest-reliability and the prognostic validity are called for in the future. PMID- 11786935 TI - Experiences with reoperation on recurrent glioblastoma multiforme. AB - OBJECTIVE: The goal was to report the treatment results after a second operation on patients with recurrent glioblastoma multiforme (GBM) and to investigate if patient's quality of life is improved and survival is lengthened. - METHODS: Thirty-eight patients (17%) out of 224 patients with glioblastoma multiforme, treated at our department from 1/93 to 12/98, underwent re-operation due to clinical and neuroradiological significant recurrence of GBM. Not included were patients who had a lower malignant tumor at first operation and GBM on second operation. All 38 patients had completed radiation therapy. - RESULTS: Overall median survival of re-operated patients was 57 weeks. Interval between 1(st) and 2(nd) operation was 42 weeks and median survival after 2(nd) operation was 23 weeks. Total survival was significantly longer in patients under 50 years at time of re-operation, a time interval longer than 26 weeks between 1(st) and 2(nd) operation, complete resection and a Karnofsky Performance Scale (KPS) >/= 90 at the time of re-operation. Only in the subgroup Karnofsky Performance Scale more or equal 90 had a significant longer survival time after reoperation (29 weeks versus 18 weeks). Based on a KPS change of at least 10 points clinical status was improved in 22 patients, unchanged in 16 patients and no patient deteriorated. No perioperative mortality has occurred. - CONCLUSIONS: Prolongation of survival time after reoperation was statistically significant only in the Karnofsky Performance subgroup. In all other groups prolongation of survival was a relative constant measure of 23%%weeks. The well known favorable prognostic indicators, such as younger age, longer event-free period, had also in our investigation the longest survival times. PMID- 11786936 TI - [Malignant brain tumors after radiation - glioblastomas after operation and radiation of meningiomas - 2 case reports]. AB - The authors report 2 cases of glioblastomas subsequent to radiation of intracranial tumors. In the first case, a 47-year old man received radiation therapy after subtotal removal of a temporobasal meningioma. In the second case, a 52-year old women underwent operation of an atypical falcine meningioma and was irradiated postoperatively. - After radiation of meningiomas the development of glioblastomas is described as a rare complication in the literature. A literature analysis of 49 radiation induced tumors revealed that there was no correlation between the radiation dosage and time interval of appearance of the second tumor. PMID- 11786937 TI - CLL cells in a brain metastasis of bronchial adenocarcinoma in a patient with three different neoplasms - case report. AB - OBJECTIVE: We report the case of a patient with three different malignancies who had a brain metastasis of bronchial adenocarcinoma with infiltrates of CLL lymphocytes and who had been operated for prostate cancer years before. - PATIENT AND RESULTS: A 72-year-old man was admitted to our department after a Jacksonian seizure. The MRI showed a left temporal mass lesion. The patient was suffering from chronic lymphocytic leukemia (CLL) for ten years, he had had surgery for prostate cancer eight years ago and the diagnosis of bronchial carcinoma was made during preoperative routine diagnostics. After neurosurgical intervention the histologic examination of the cerebral mass lesion disclosed metastasis of a PSA negative adenocarcinoma with perivasal infiltrates of lymphocytic leukemic cells. - DISCUSSION: There are few reports about patients with three primary malignancies. CLL may play a role in enabling tumor cells to escape the immune response and could facilitate development of the prostate cancer and of a bronchial adenocarcinoma as secondary cancers in this patient. The combined occurrence of adenocarcinoma cells and CLL lymphocytes in the brain metastasis can be explained by impairment of the blood-brain-barrier in the carcinoma metastasis enabling extravasation of circulating leukemic cells. PMID- 11786938 TI - Trigeminal neuralgia caused by contralateral cerebellopontine angle meningioma - case report. AB - A large meningioma located in the cerebellopontine angle was an unusual cause for contralateral trigeminal neuralgia. The mass effect displaced the basilar artery affecting the contralateral trigeminal nerve in vicinity of the brain stem. After radical microsurgical removal ot the tumour, the trigeminal neuralgia completely disappeared. PMID- 11786939 TI - [Pain of the trigeminal nerve as the first symptom of a metastasis from an oesohaguscarcinoma in Meckel's cave - case report]. AB - Pain in all three divisions of the trigeminal nerve is in over 65% of all cases the first symptom of a tumour in Meckel's cave. Tumors in this location make up only 0,5% of all intracranial tumours. The most common are trigeminal schwannomas and meningeomas. A metastases as a cause of trigeminal pain is a rare description in the literature so far. We describe a patient with trigeminal pain and a tumour in Meckels's cave shown in the MRI, who were operated in our department. The histological examination of the tumour resulted in the diagnosis of metastatic carcinoma of an until then unknown oesophaguscarcinoma. - Although metastatic tumours are rare, we could show with our case, that they have to be included in differential dignostic considerations. PMID- 11786940 TI - [Hugo Ruf: 90 years old as a time witness--a life devoted to neurosurgery]. PMID- 11786941 TI - A new predictor of improvement in regional left ventricular function assessed by ST/HR slope derived from ST elevation on exercise testing in patients with healed myocardial infarction. AB - This study evaluates the clinical usefulness of ST/HR slope derived from ST elevation on exercise to predict the improvement in regional wall motion following coronary revascularization in patients with healed myocardial infarction. We studied 58 patients with a diseased, infarct-related and single vessel coronary artery. The decline calculated from the final 12 data points relating ST-segment elevation to heart rate during exercise were derived (ST/HR slope). Hypokinesis in the infarcted region was assessed by the centerline method and expressed in terms of standard deviations (SD/chord). The increase more than 30% of the SD/chord, which was defined as the improvement in regional wall motion, was seen in 23 of the 30 patients with a ST/HR slope of > or = 5.0 (microV/bpm), and in 4 of the 28 patients with a ST/HR slope <5.0 (microV/bpm) (P <.0001). Thus, a ST/HR slope derived from ST elevation on exercise identifies subgroups of patients who show a good recovery of regional wall motion. PMID- 11786942 TI - Electrocardiographic comparison of myocardial salvage with primary revascularization versus thrombolysis in inferior myocardial infarction. AB - Primary revascularization (PR) and thrombolytic therapy (TT) reduce infarct size and mortality in patients with ST-segment elevation acute myocardial infarction (AMI). Electrocardiogram methods can determine the extent of myocardial salvage with different AMI therapies by comparing infarct size predicted by initial ST segment changes and infarct size estimated by later quantitative QRS scores. In a community hospital setting, we used quantitative electrocardiogram methods to estimate infarct size and myocardial salvage associated with TT and PR amongst 50 patients presenting with inferior ST-segment elevation AMI. Baseline and electrocardiogram characteristics did not differ between TT (n = 29) and PR (n = 21) patients. There was no difference in median myocardial salvage (%) between TT vs. PR groups, (38.3% vs. 44.9% respectively, P =.66). Among patients with inferior AMI, myocardial salvage was achieved with both TT and PR therapy and did not differ significantly between reperfusion strategies. PMID- 11786943 TI - Beat-to-beat QT interval variability associated with acute myocardial ischemia. AB - Beat-to-beat QT interval variability (QTV) quantifies lability in ventricular repolarization. We hypothesized that myocardial ischemia destabilizes ventricular repolarization and increases QTV. We analyzed 2-hour 2-lead digitized electrocardiogram records of 68 patients in the European ST-T Database. All patients had ischemic episodes during the 2-hour record, annotated by the developers of the database. We determined the normalized QTV (QTVnorm), QT variability index (QTVI), and normalized heart rate variability (HRVnorm) for each 5-minute epoch by automated analysis. QTVnorm was greater during ischemic episodes than during nonischemic episodes (1.41 +/- 0.77 vs. 0.88 +/- 0.23, P <.0001). There was no significant difference in HRVnorm between ischemic and nonischemic episodes (1.22 +/- 0.63 vs. 0.94 +/- 0.18, not significant). The QTVI was higher during ischemic episodes than during nonischemic episodes (0.14 +/- 0.31 vs. -0.051 +/- 0.12, P <.0001). Acute ischemia is associated with labile ventricular repolarization, which manifests as enhanced beat-to-beat QT interval variability. The association between ischemic repolarization liability and arrhythmic risk deserves further study. PMID- 11786944 TI - Use of a novel rule-based expert system in the detection of changes in the ST segment and the T wave in long duration ECGs. AB - The development of a new fast and robust computerised system is examined in detecting electrocardiogram (ECG) changes in long duration ECG recordings. The system distinguishes these changes between ST-segment deviation and T-wave alterations and can support the produced diagnosis by providing explanations for the decisions made. The European Society of Cardiology ST-T Database was used for evaluating the performance of the system. Sensitivity and positive predictive accuracy were the performance measures used and the proposed system scored 92.02% and 93.77%, respectively, in detecting ST-segment episodes and 91.09% and 80.09% in detecting T-wave episodes. By using the chi-square test we also compared the performance of the system between ECG recordings with minimal and substantial amount of noise. The sensitivity of the proposed system is higher than of other algorithms reported in the literature and the positive predictive accuracy is comparable to, or better than, most of them. PMID- 11786945 TI - Contribution of body surface mapping to clinical outcome after surgical ablation of postinfarction ventricular tachycardia. AB - This article investigates the influence of body surface mapping on outcome of ventricular antiarrhythmic surgery. Preoperative mapping is advocated to optimize map-guided antiarrhythmic surgery of postinfarction ventricular tachycardia. We sequentially analyzed the results of catheter activation sequence mapping, body surface mapping, and intraoperative multielectrode mapping in 54 patients and made a comparison with 30 control patients (group B) in whom catheter activation sequence mapping was omitted. Endpoints were actuarial survival, freedom of arrhythmia, and comparability of the localisation of sites of ventricular tachycardia origin. A total of 128 morphologically different monomorphic sustained ventricular tachycardias were mapped in group A. In group A, 87 ventricular tachycardias were mapped preoperatively with body surface mapping and 30 ventricular tachycardias with catheter activation sequence mapping. In 19 of 24 ventricular tachycardias (79%) that were localized with both mapping methods the ventricular tachycardia exit site was similar. In-hospital death was 1 of 85 (1.2%). Actuarial freedom from ventricular arrhythmias at 4-year follow-up was 74.1 +/- 6.0% in group A vs. 90.0+/-5.5% in group B (P =.10). In group A 14 of 54 patients died (29.6%), whereas 4 of 30 patients (13.3%) died in group B (P =.09). Arrhythmia freedom and survival is as good in patients mapped with body surface mapping only as in patients mapped with body surface mapping and catheter activation sequence mapping. PMID- 11786946 TI - Transthoracic defibrillation of dogs with Edmark, biphasic, and quadriphasic waveforms. AB - Patients with high transthoracic impedance are reported to be at higher risk of poor outcomes when treated by present defibrillators. This study evaluates the defibrillation efficacy of biphasic truncated exponential (BTE), quadriphasic truncated exponential (QTE), and Edmark waveforms at simulated low, average, and high impedance levels. Waveforms were tested at 2 energy levels in random order in anesthetized dogs (n = 15, 16.9 +/- 1.2 kg), and a supplemental study estimated the ED50 peak current for BTE and QTE at a simulated high impedance level. Overall, BTE and QTE were equivalent, and both were superior to Edmark at equal delivered energies (P<.0001). However, in simulated high impedance patients at 24 J, QTE was superior to BTE (71% vs. 49%, P =.011 (borderline significance see text)). Supplemental study, QTE mean ED50 peak current was lower than BTE (7.9 vs. 8.9 A, P =.0049). QTE and BTE waveforms were superior to Edmark at all studied conditions, but QTE appears to be superior to BTE in simulated high impedance patients. PMID- 11786947 TI - The influence of tumor size on the electrocardiographic changes in patients with left atrial myxoma. AB - The authors assessed the usefulness of the electrocardiography in patients with left atrial myxoma. The authors retrospectively reviewed the records of 15 patients with left atrial myxoma before and after tumor excision. The 12-lead electrocardiogram presented the P-wave abnormality shown by a broad P wave in lead II (PDII) and/or a deep and broad negative P terminal force in lead V1 (PTFV1). These abnormal findings were shown in the 13 patients whose tumor weight was 16 g or more. However, the other 2 patients whose tumor weight were 7 g or less did not have a prolonged PDII or an increased PTFV1. Both PDII and PTFV1 were correlated not only with the tumor size but also with the left atrial dimension and/or the left atrial pressure. These P-wave abnormalities were markedly improved or disappeared, and the left atrial dimension and pressure decreased immediately after tumor excision. The increasing size of the tumor brings about the P-wave abnormalities, which may result from enlargement of the left atrial cavity. It is suggested that while not specific the 12-lead ECG findings of PDII and PTFV1 may be useful for detecting a myxoma weighting 16 g or more, but was an insensitive technique for smaller ones. PMID- 11786948 TI - Differentiation of atrial rhythms from the electrocardiogram with coherence spectra. AB - Automated electrocardiogram (ECG) interpretation systems fail to reliably discriminate atrial fibrillation from sinus rhythm and other more regular atrial arrhythmias. Previously, magnitude-squared coherence (MSC), a frequency domain measure of the linear phase relation between 2 signals, has been shown to be a reliable discriminator of fibrillatory and nonfibrillatory cardiac rhythms when applied to intracardiac electrograms. This study determines whether MSC, when applied to the surface electrocardiogram, would discriminate between atrial fibrillation and nonfibrillatory atrial rhythms. MSC was analyzed by using 2 surface leads of a 10-second ECG. For 68 ECG recordings (23 sinus rhythm, 22 atrial flutter, and 23 atrial fibrillation), MSC was computed between leads II and V1 and the mean MSC in several frequency bands was examined. The performance of MSC was compared to previously published measures of ventricular irregularity and percent power in discriminating atrial fibrillation from nonfibrillatory rhythms. As hypothesized, atrial fibrillation exhibited low coherence in the 2 to 9 Hz band while nonfibrillatory atrial rhythms exhibited relatively moderate to high levels of coherence in the same frequency band. Mean MSC in the 2 to 9 Hz band was significantly lower for atrial fibrillation (range, 0.04 to 0.48; mean +/- SD: 0.15 +/- 0.11) than for sinus rhythm (range, 0.18 to 0.81; 0.47 +/- 0.17) (P <.0005) and atrial flutter (range, 0.06 to 0.80; 0.44 +/- 0.21) (P <.0005). Mean MSC in the 2 to 9 Hz band showed less overlap between atrial fibrillation and atrial flutter than R-R variability and percent power. However, R-R variability showed less overlap between atrial fibrillation and sinus rhythm than mean MSC and percent power. Thus, MSC and RRV both discriminate atrial fibrillation from more organized atrial rhythms. Conversely, percent power was highly variable for both atrial fibrillation and organized atrial rhythms. Results suggest that MSC applied to surface ECG may be used to quantify rhythm organization. PMID- 11786949 TI - Double ventricular response caused by longitudinal dissociation in the his bundle. AB - Electrocardiograms were taken from a 36-year-old woman with normal sinus rhythm in which 4 types of QRS complexes and 2 types of fusion QRS complexes were found in configuration. To interpret this arrhythmia, we proposed 3 unique mechanisms: a) double ventricular response through the fast pathway mainly directing to the right bundle branch and the slow pathway mainly directing to the left bundle branch, b) longitudinal dissociation in the His bundle, and c) transverse conduction in the lower edge of the dissociation. Although functional longitudinal dissociation in the atrioventricular node has been reported, longitudinal dissociation in the His bundle is a rare arrhythmia. PMID- 11786950 TI - Ablation of nonparoxysmal A-V nodal tachycardia. AB - The present study describes the successful radiofrequency ablation of an uncommon type of A-V nodal tachycardia. Electroanatomical mapping of the right atria was used to locate the region of the earliest atrial activation and allowed for positioning of the ablation catheter and a successful 25-watt radiofrequency burn in this area terminating the tachycardia. The ability to visualize multiple projections of pertinent intracardiac structures allows a more rapid and systematic approach by marking all ablation points even in the presence of AV block or AV dissociation. Consequently, repeated burns can be eliminated in previously treated areas by electroanatomical mapping of the earliest depolarization and leading pacemaker. PMID- 11786951 TI - Unusual atrial response to electrical pacing during ischemia. AB - A 76-year-old woman with a dual chamber pacemaker underwent coronary intervention of the right coronary artery for unstable angina. After the procedure, she had recurrent chest pain, and after the repeat angiography showed reduced coronary flow in the distal vessel, she underwent emergent coronary artery bypass grafting. During this course of events, the stimulation-excitation interval of the atrium was prolonged and paralleled with the severity of the ischemia. Additionally, a transient but unusual electrophysiological phenomenon was observed that the atrium could be captured at a rate of 90 ppm, but not 80 ppm. This phenomenon might be caused by phase 4 depolarization or rate-dependent facilitation of conduction in the ischemic atrium. PMID- 11786953 TI - Ubiquitin-mediated degradation of cellular proteins in health and disease. PMID- 11786954 TI - Current and novel immunosuppressive therapy for autoimmune hepatitis. AB - Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with autoimmune hepatitis (AIH) and results in remission induction in over 80% of patients. Sustained response to therapy may result in substantial regression of fibrosis even in advanced cases. The outcome of rapid withdrawal of immunosuppression is disease relapse in many patients. Consequently, the use of 2 mg/kg/d of azathioprine as a sole agent to maintain remission has been widely accepted in clinical practice. Persistent severe laboratory abnormalities or histologic abnormalities such as bridging necrosis or multilobular necrosis are absolute indications for treatment based on controlled clinical trials, but debate exists as to whether all patients with AIH need treatment. Examination of liver tissue remains the best method of evaluating both treatment response and need for treatment in patients who have little biochemical activity. Alternative strategies in patients who have failed to achieve remission on "standard therapy" of corticosteroids with or without azathioprine or patients with drug toxicity include the use of cyclosporine, tacrolimus, or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease. In this review we examine current management strategies of AIH, and evaluate available data pertaining to the use of novel immunosuppressive agents in this condition. PMID- 11786955 TI - Contribution to antimitochondrial antibody production: cleavage of pyruvate dehydrogenase complex-E2 by apoptosis-related proteases. AB - Patients with PBC produce a directed, specific response to a single immunodominant autoepitope of PDC-E2 within the inner lipoyl domain. In contrast, immunized animals react to multiple epitopes and rarely recognize the inner lipoyl domain. In other autoimmune diseases, apoptosis plays a critical role in antigen presentation; the caspases and granzyme B are the key proteases in the generation of autoepitopes. To determine the specific cleavage pattern of full length recombinant PDC-E2, we performed in vitro digestion with caspases-3, -6, 8 and granzyme B. The resulting fragments were immunoblotted and probed with an extensive panel of monoclonal anti-PDC-E2 antibodies and sera from patients with PBC. Interestingly, on granzyme B digestion, PDC-E2 lost reactivity, suggesting the destruction of the immunodominant epitope. Because this site contains the major epitope for both B cells and T cells, it suggests that granzyme B is unlikely to be involved in generation of autoepitopes in primary biliary cirrhosis (PBC). In contrast, following treatment with the caspase enzymes, immunoreactive fragments were generated. Indeed, by confocal microscopy, activated caspase-3 is found in the marginal hepatocytes and bile ducts. Moreover, caspase-3 staining was strongest in the small intrahepatic bile ducts, the major site of tissue destruction in PBC. In conclusion, these data suggest that following apoptosis, the caspase family of proteolytic enzymes have the potential to generate immunogenic fragments that contribute to the autoantigen reservoir and the production of antimitochondrial antibodies. These findings are also consistent with the generation of an autoimmune response against an intracellular antigen that evades catabolism during apoptosis. PMID- 11786956 TI - Oligoclonal expansion of T cell receptor V beta 2 and 3 cells in the livers of mice with graft-versus-host disease. AB - The nonsuppurrative destructive cholangitis lesions in the B10.D2 (donor) into BALB/c (host) mouse graft-versus-host disease (GVHD) model are dependent on CD4 T cells that use a T cell receptor-beta chain variable region (Vbeta) repertoire, which is heavily biased toward Vbeta2 and Vbeta3 usage. We hypothesized that liver Vbeta2(+) and Vbeta3(+) CD4 T cells originate from donor mice and recognize BALB/c minor histocompatibility alloantigens and BALB/c endogenous retroviral superantigen-6, respectively. To test this hypothesis, we determined the donor:host chimera status of infiltrating liver lymphocytes and the clonal states of liver Vbeta2(+) and liver Vbeta3(+) CD4 cells isolated from GVHD mice. A limited donor TCR Vbeta repertoire composed of Vbeta1(+), 2(+), 3(+), 4(+), 6(+), and 8(+) cells infiltrated the livers of GVHD mice on day 3. Consistent with a response to immunodominant host minor histocompatibility antigens, we detected oligoclonal liver Vbeta2(+) T cells in 40% of GVHD mice studied on day 3 and in 100% of GVHD mice studied on day 14. Typical of superantigen stimulation, extremely polyclonal liver Vbeta3(+) T cells were detected in 100% of GVHD mice studied on day 3 and 40% of GVHD mice studied on day 14. Yet, the liver Vbeta3(+) T cells in 60% of the day 14 GVHD mice were oligoclonal, pointing to a response to minor histocompatibility antigens. PMID- 11786957 TI - Adenovirus-mediated increase in HNF-3beta or HNF-3alpha shows differences in levels of liver glycogen and gene expression. AB - We previously generated a transgenic mouse line (T-77) in which increased hepatic expression of the hepatocyte nuclear factor-3beta (HNF-3beta) protein was used to assess its role in hepatocyte-specific gene transcription. The T-77 transgenic mice displayed elevated serum bile acid and bilirubin levels and a complete absence of hepatic glycogen storage. These postnatal liver defects were associated with diminished expression of hepatocyte genes involved in gluconeogenesis and bile acid transport as well as reduced levels of hepatocyte transcription factors. In this study, we show that mouse tail vein injections of adenovirus expressing the rat HNF-3beta (AdHNF3beta) cDNA efficiently increased its levels throughout the liver lobule and recapitulated the T-77 transgenic liver phenotype within several days postinfection. Likewise, the AdHNF3beta infected liver phenotype was associated with reduced hepatic expression of genes involved in glucose homeostasis, bile acid transport, and bilirubin conjugation, which were not found with control adenovirus infections. These studies show that adenovirus-mediated gene transfer is an effective method for rapid hepatic increases in transcription factor levels to determine in vivo target genes. In contrast, AdHNF3alpha-infected liver displayed only a transient reduction in hepatic glycogen levels and was associated with less severe decreases in hepatic expression of gluconeogenic and bilirubin metabolism genes. Consistent with these findings, only T-77 transgenic and AdHNF3beta-infected liver exhibited diminished hepatic expression of the HNF-6 transcription factor, suggesting that reduced HNF 6 levels contribute to diminished HNF-3beta-specific transcriptional activity. PMID- 11786958 TI - Interleukin-6 from intrahepatic cells of bone marrow origin is required for normal murine liver regeneration. AB - Interleukin-6 (IL-6) is required for normal liver regeneration, but the specific cellular source of this growth factor is unknown. We investigated whether this signal originates from the resident macrophage, the Kupffer cell. Using a murine model of bone marrow transplantation, we replaced recipient bone marrow-derived cells, including Kupffer cells, with cells of donor genetic phenotype. Recipients deficient in IL-6 (IL-6(-/-)) were lethally irradiated, then rescued with 10(7) donor bone marrow cells capable of expressing IL-6 (IL-6(+/+)). Conversely, IL 6(+/+) recipients received IL-6(-/-) marrow. Successful engraftment was measured by the presence of the Y chromosome SRY locus in the livers of female recipients receiving male marrow, in situ IL-6 expression by Kupffer cells, and up regulation of IL-6 in splenocytes after activation with lipopolysaccharide (LPS). Kupffer cell isolation in IL-6(-/-) females receiving IL-6(+/+) male marrow clearly showed the presence of the SRY locus and IL-6 disrupted allele, whereas males receiving female marrow demonstrated no SRY or IL-6 signals, confirming the extent of replacement. Replacement of these cells in IL-6(-/-) mice with IL 6(+/+) bone marrow successfully restored the regenerative response after partial hepatectomy (PHx) as indicated by signal transduction and activator of transcription 3 (STAT3) activation and hepatocyte DNA replication. Alternatively, complete replacement of Kupffer cells in IL-6(+/+) mice by transplantation with IL-6(-/-) cells significantly inhibited liver regeneration and was partially restored by administration of IL-6. This investigation demonstrates a paracrine mechanism by which cells of bone marrow origin, most likely Kupffer cells, regulate the regenerative capacity of the hepatocyte through IL-6 expression. PMID- 11786959 TI - Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury. AB - During chronic liver injury, transforming growth factor beta (TGF-beta) plays a prominent role in stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells (HSCs). On the other hand, Smad 7 was recently shown to antagonize the TGF-beta-induced activation of signal transducing Smads (2 and 3). In this study, we investigated the regulatory mechanisms of the TGF-beta signals in rat HSCs during acute liver injury and myofibroblasts (MFBs) during chronic liver injury, focusing on the roles of Smad 2 and antagonistic Smad 7. In acute liver injury, HSC-derived TGF-beta increased plasminogen activator inhibitor type 1 (PAI-1) and alpha2(I) procollagen (COL1A2) transcripts. Smad 2 in HSCs during liver injury and primary cultured HSCs were activated by an autocrine mechanism, because high levels of Smad 2 phosphorylation and induction of PAI-1 transcript by TGF-beta were observed in HSCs. Thereafter, Smad 7 induced by TGF-beta negatively regulated the Smad 2 action. These results indicated that endogenous TGFbeta-mediated Smad 7 in HSCs terminated the fibrotic signals mediated by signal-transducing Smads, and might be involved in the transient response to autocrine TGF-beta signal after acute liver injury. By contrast, Smad 7 was not induced by the autocrine TGF-beta signal, and constitutive Smad 2 activation was observed in MFBs throughout chronic liver injury, although Smad 7 could inhibit the TGF-beta signal requiring Smad 2 phosphorylation by activated TGF-beta receptor in cultured MFBs. This constitutive phosphorylation of Smad 2 by endogenous TGF-beta under a low level of Smad 7 could be involved in the progression of liver fibrosis. PMID- 11786960 TI - Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. AB - The alcohol-inducible cytochrome P450 2E1 (CYP2E1) is expressed mainly in hepatocytes and generates reactive oxygen species (ROS). To better understand how hepatic stellate cells (HSC) become activated in the presence of oxidative stress and evaluate whether CYP2E1-derived ROS activate stellate cells, we coincubated primary stellate cells with HepG2 cells, which do (E47 cells) or do not (C34 cells) express CYP2E1. Morphologic changes and loss of lipid droplets were more apparent in the stellate cells cocultured with E47 cells. There was a more pronounced increase in alpha-smooth muscle actin (alpha-sma), intracellular and secreted collagen type I protein, and intra- and extracellular H(2)O(2) and lipid peroxidation products in stellate cells coincubated with E47 cells. Expression of collagen in stellate cells did not change when cocultured with HepG2 cells expressing a different P450, CYP3A4. Stellate cells cultured on Matrigel expressed increased alpha-sma and collagen when incubated with E47 cells. The increase in collagen production by coculture with E47 cells was prevented by antioxidants, by CYP2E1 inhibitors, and by transfected antisense CYP2E1. The addition of arachidonic acid plus ferric nitrilotriacetate (Fe-NTA), agents that potentiate oxidative stress, further induced collagen protein in the E47 coculture. Stellate cell proliferation was greater in the E47 coculture, and this was partially abrogated by catalase and vitamin E. These results show that hepatocytes containing CYP2E1 release diffusible mediators including ROS, which can activate HSC. Thus, besides perturbing the homeostasis of hepatocytes, CYP2E1 derived diffusible oxidants may also interact with stellate cells and contribute to hepatic fibrosis. PMID- 11786961 TI - gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver. AB - B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/ 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3 fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5 fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver. PMID- 11786962 TI - Regulation of the alpha-fetoprotein gene by the isoforms of ATBF1 transcription factor in human hepatoma. AB - We investigated mechanisms regulating expression of alpha-fetoprotein (AFP) in 3 human hepatoma cell lines, HuH-7, HepG2, and huH-1, producing high, medium, and low levels of AFP, respectively. The silencer, a negative cis-acting element of the AFP gene, was highly activated in huH-1 and HepG2 to repress AFP enhancer activity by 91%, whereas only 26% repression was observed in HuH-7. To account for the difference in AFP production between HepG2 and huH-1, we investigated the roles of two isoforms of the AT motif-binding factor 1 (ATBF1) transcription factor, ATBF1-A and -B. Cotransfection assays showed that the ATBF1 isoforms regulated the AFP gene differently in HepG2 and huH-1. In huH-1 and HuH-7, both ATBF1 isoforms suppressed strongly enhancer activity and slightly promoter activity. In HepG2, on the other hand, ATBF1-A suppressed the enhancer and promoter activities, but surprisingly, ATBF1-B was found to stimulate enhancer activity while showing no effect on the promoter. Levels of ATBF1-A mRNA were similar in all 3 cell lines, whereas the expression ATBF1-B mRNA varied greatly, with the highest level seen in HepG2 followed by huH-1 and HuH-7. These results suggest that, in HepG2, ATBF1-B may have a dominant negative effect to relieve the transcriptional repression caused by its isoform. In support of this view, we found that the N-terminal region specific to the ATBF1-A molecule possessed transcriptional repressor activity. Thus, the use of the ATBF1 variants as well as the silencer may provide a unique mechanism that contributes to the determination of AFP levels in human hepatoma cell lines. PMID- 11786963 TI - The atrial natriuretic peptide and cGMP: novel activators of the heat shock response in rat livers. AB - Preischemic treatment with atrial natriuretic peptide (ANP) attenuates ischemia reperfusion injury of the rat liver via cyclic guanosine monophosphate (cGMP). The attenuated activation of nuclear factor kappaB (NF-kappaB) seems to contribute to this effect. The aim of this study was to determine whether heat shock proteins are involved in these molecular pathways. Livers of male Sprague Dawley rats were continuously perfused with Krebs-Henseleit (KH) buffer with or without ANP or 8-Br-cGMP. In different experiments livers were perfused with or without ANP for 20 minutes, kept in cold storage solution for 24 hours, and reperfused. Activation of heat shock transcription factor (HSF) (by electrophoretic mobility shift assay), heat shock protein 70 (HSP70), and glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA (by reverse transcription polymerase chain reaction [RT-PCR]), as well as HSP70 (by Western blot) were investigated in freeze-clamped liver samples. During continuous perfusion ANP as well as 8-Br-cGMP activated HSF, HSP70 protein concentrations paralleled HSF activation. ANP pretreated livers exhibited elevated HSF after 24 hours of ischemia and elevated HSP70 mRNA levels during reperfusion. ANP prevented the marked decrease of HSP70 protein during reperfusion. Coimmunoprecipitation studies showed increased binding of HSP70 to inhibitory factor kappaB (IkappaB) in ANP-treated livers. In conclusion, we showed the cGMP-mediated activation of HSF by ANP, which resulted in elevated HSP70 mRNA and protein concentrations and correlated with enhanced binding of HSP70 to IkappaB. This could be an important mechanism of ANP-mediated prevention of hepatic preservation damage. PMID- 11786964 TI - Correction of CFTR malfunction and stimulation of Ca-activated Cl channels restore HCO3- secretion in cystic fibrosis bile ductular cells. AB - In view of the occurrence of hepatobiliary disorders in cystic fibrosis (CF) this study addresses the role of the cystic fibrosis transmembrane conductance regulator (CFTR) and of Ca(2+)-activated Cl(-) channels in promoting HCO3- secretion in bile ductular cells. Human cholangiocytes were isolated from control livers and from 1 patient with CF (DeltaF508/G542X mutations). Single channel and whole cell currents were analyzed by patch clamp techniques, and HCO3- secretion was determined by fluorometric analysis of the rate of recovery of intracellular pH following alkaline loading. In control cholangiocytes, both cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) catalytic subunit, activated CFTR Cl(-) channels that exhibited a nonrectifying conductance of 8 pS and appeared in clusters. Activation of Cl(-) current by cAMP was associated with an increase in the rate of HCO3- secretion. The basal rate of HCO3- secretion was lower in CF than in control cholangiocytes. In both control and CF cholangiocytes, raising intracellular Ca(2+) concentrations with ionomycin led to a parallel activation of Cl(-) current and HCO3- secretion. Consistent with reports that premature stop codon mutations (class I; e.g., G542X) can be read over by treatment with aminoglycoside antibiotics, exposure of CF cholangiocytes to gentamicin restored activation by cAMP of Cl(-) current and HCO3- secretion. The observation that activation of Ca(2+)-dependent Cl(-) channels can substitute for cystic fibrosis transmembrane conductance regulator (CFTR) in supporting HCO3- secretion and the efficacy of gentamicin in restoring CFTR function and HCO3- secretion in class I mutations are of potential clinical interest. PMID- 11786965 TI - Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States. AB - Studies assessing morbidity and mortality in obese patients undergoing orthotopic liver transplantation (OLT) have produced conflicting results, mainly because of the small sample size. The objective of our study was to determine graft and patient survival in obese adults receiving OLT in the U.S. between 1988 through 1996 using the United Network for Organ Sharing (UNOS) database. Among the 23,675 transplantations performed during the 9-year study period, 18,172 (75%) patients fulfilled the inclusion criteria. Of these, 8,382 (46%) were nonobese (body mass index [BMI] < 25 kg/m(2)), 5,913 (33%) were overweight (BMI, 25.1-30 kg/m(2)), 2,611 (14%) were obese (BMI, 30.1-35 kg/m(2)), 911 (5%) were severely obese (BMI, 35.1-40 kg/m(2)), and 355 (2%) were morbidly obese (BMI, 40.1-50 kg/m(2)). The outcome measures assessed were immediate (30-day), 1-, 2-, and 5-year patient survival. Obese groups had a higher proportion of women, a greater prevalence of cryptogenic cirrhosis (P <.05) and diabetes (P <.05), and a higher serum creatinine. Primary graft nonfunction, and immediate, 1-year, and 2-year mortality were significantly higher in the morbidly obese group (P <.05). Five year mortality was significantly higher both in the severely and morbidly obese subjects (P <.05), mostly as a result of adverse cardiovascular events. Kaplan Meier survival was significantly lower in morbidly obese patients, and morbid obesity was an independent predictor of mortality. Obesity is associated with a significant increase in long-term mortality, mostly as a result of cardiovascular events. Weight loss should be recommended for all patients awaiting a liver transplantation, especially if their BMI is more than 35 kg/m(2). PMID- 11786966 TI - High frequency of epithelial chimerism in liver transplants demonstrated by microdissection and STR-analysis. AB - It has recently been shown that epithelial cells derived from stem cells originating outside the liver are integrated into liver allografts. Whether epithelial intragraft chimerism protects transplants from rejection or chronic transplant dysfunction, and whether it interferes with recurrence of primary liver disease, is not known. Twenty-seven sequential biopsies derived from 9 liver-transplant recipients were studied for chimerism of hepatocytes and cholangiocytes. The target cells were isolated by laser microdissection after cytokeratin immunolabeling and genotyped using DNA analysis of a highly polymorphic short tandem repeat. Irrespective of whether early (up to 4 weeks) or late (more than 12 months) posttransplantation biopsies were studied, cholangiocyte chimerism was almost constantly found in 91% of the samples. No significant differences occurred between samples derived from patients with chronic organ dysfunction (n = 3), recurrent hepatitis (n = 3), or mild, unspecific changes (n = 3). By contrast, hepatocyte chimerism tended to occur later (55% vs. 22%) and appeared to be associated with recurrent hepatitis (67% vs. 27%). In this respect, chronic organ dysfunction did not differ from mild, unspecific changes. While cholangiocyte chimerism represents a constant and early phenomenon in liver transplantations, an enhanced chimeric integration of recipient-derived hepatocytes can be observed in recurrent hepatitis, supporting the concept of an increased recruitment of extrahepatic progenitor cells to the liver in chronic hepatitis. PMID- 11786967 TI - Accuracy of bile duct changes for the diagnosis of chronic liver allograft rejection: reliability of the 1999 Banff schema. AB - Chronic rejection (CR) after liver transplantation is thought to be a dynamic and potentially reversible process. The Banff working group has developed recommendations for its histopathologic staging. The 1999 Banff classification of CR (i.e., bile duct dystrophy >50% and/or bile duct loss >20%) was applied to: 1) biopsies from patients retransplanted for CR (N = 19) and pathologies other than CR (N = 21) to evaluate its specificity and sensitivity, especially of the early stage lesions of CR; and 2) biopsies from nonretransplanted patients (N = 21) to evaluate the evolution of CR lesions. Atypical forms of CR were also described. Including an early stage into the definition of CR has resulted in a much higher sensitivity for its diagnosis, as compared with the former classification (i.e., bile duct loss >50%) (89% vs. 33%; P =.0001), while keeping an acceptable specificity (74% vs. 100%; P =.03). In 55% of the nonretransplanted patients, CR lesions were reversible. No histologic feature reliably predicted CR outcome. Transient lobular hepatitis, unrelated to viral infection, and veno-occlusive disease were seen significantly more often in the CR group (P =.04 and P =.03, respectively). We conclude that the application of the 1999 Banff classification is superior to the previous classification for the diagnosis of CR. However, limited information can be drawn regarding the outcome of CR based on histology alone. Transient lobular hepatitis, unrelated to viral infection and veno occlusive disease, may be an unusual expression of CR. PMID- 11786968 TI - Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. AB - Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25 Dihydroxyvitamin D(3) has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. In this study VDR polymorphisms were analyzed in 123 patients with AIH, 74 patients with PBC, and 214 controls. VDR polymorphisms were assessed by BsmI, TaqI, ApaI, and Fok endonuclease digestion after specific polymerase chain reaction (PCR) amplification. We found a significant association between the BsmI polymorphisms in PBC patients in comparison with controls (chi(2) = 9.49, P =.009). Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls (chi(2) = 9.71, P =.008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases. PMID- 11786969 TI - TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy. AB - Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery or liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) represents a new treatment alternative, but its long term effect on BCS outcome has not been evaluated. Twenty-one patients with BCS consecutively admitted to our unit were evaluated. The mean follow-up was 4 +/- 3 years. Seven patients had nonprogressive forms and were successfully controlled with medical therapy; 1 case, with a short-length hepatic vein stenosis was successfully treated by angioplasty. All 8 patients are alive and asymptomatic. The remaining 13 patients, had a TIPS because of clinical deterioration (in one of them, because early TIPS thrombosis a successful side-to-side portacaval shunt [SSPCS] was performed) followed by an improvement in clinical condition. However, a patient with fulminant liver failure before TIPS insertion, died 4 months later and another patient with cirrhosis at diagnosis had liver transplantation 2 years later. The remaining 11 patients are alive and free of ascites. In 3 of these patients TIPS is patent after 3, 6, and 12 months. The remaining 8 patients developed late TIPS dysfunction. In two of these cases, after angioplasty and restenting, TIPS is patent after a follow-up of 9 and 80 months. In 5 other patients, recurring TIPS occlusion was not further corrected because no signs of portal hypertension were present. In conclusion, in patients with BCS uncontrolled with medical therapy, TIPS is a highly effective technique that is associated with long-term survival. PMID- 11786970 TI - Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. AB - The extensive use of invasive procedures and of long-term norfloxacin prophylaxis in the management of cirrhotic patients may have influenced the epidemiology of bacterial infections in cirrhosis. We conducted a prospective evaluation of all bacterial infections diagnosed in patients with cirrhosis in a Liver Unit between April 1998 and April 2000. A total of 405 patients presented 572 bacterial infections in 507 admissions. Spontaneous bacterial peritonitis was the most frequent infection (138 cases). Gram-positive cocci were responsible for 53% of total bacterial infections in the study, being the main bacteria isolated in nosocomial infections (59%). Patients requiring treatment in an intensive care unit and those submitted to invasive procedures presented a higher rate of infections caused by gram-positive cocci (77% vs. 48%, P <.001 and 58% vs. 40%, P <.02, respectively). Fifty percent of culture-positive spontaneous bacterial peritonitis in patients on long-term norfloxacin administration (n = 93) and 16% in patients not receiving this therapy (n = 414) were caused by quinolone resistant gram-negative bacilli, P =.01. The rate of culture-positive spontaneous bacterial peritonitis caused by trimethoprim-sulfamethoxazole-resistant gram negative bacilli was also very high in patients on long-term norfloxacin administration (44% vs. 18%, P =.09). In conclusion, infections caused by gram positive cocci have markedly increased in cirrhosis. This phenomenon may be related to the current high degree of instrumentation of cirrhotic patients. Quinolone-resistant spontaneous bacterial peritonitis constitutes an emergent problem in patients on long-term norfloxacin prophylaxis, with trimethoprim sulfamethoxazole not being a valid alternative. PMID- 11786971 TI - Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin. AB - Cholestatic liver injury is associated with an increased susceptibility toward endotoxin-induced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R(-/-)) mice, which are unresponsive to IL-1alpha and IL-1beta, and normal IL-1R(+/+) mice. Bdl elicited increases in hepatic IL-1alpha and IL-1beta messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R(-/-) and IL-1R(+/+) mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in sham-operated IL-1R(-/-) and IL-1R(+/+) mice were largely similar, but cholestatic IL-1R(-/-) mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1alpha and IL 1beta are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl. PMID- 11786972 TI - Hyperdynamic circulation in portal-hypertensive rats is dependent on central c fos gene expression. AB - Portal hypertension is associated with hyperdynamic circulation, but the pathogenesis remains unclear. To clarify the role of central cardiovascular regulatory mechanisms, several protocols were conducted in rats with portal hypertension due to portal vein stenosis (PVS). Neuronal activation was quantified by immunohistochemical staining for Fos, the protein product of the c fos gene. Fos expression in several brain nuclei with cardiovascular-regulatory roles was examined at 1, 3, 5, and 10 days following PVS surgery. This was correlated with development of cardiovascular changes measured at the same time points. Finally, Fos expression in the nucleus tractus solitarius (NTS) was blocked by local microinjection of c-fos antisense oligonucleotides twice daily for 5 days following PVS. The results showed that Fos-positive neurons were significantly increased in the paraventricular nucleus of hypothalamus, supraoptic nucleus, ventrolateral medulla, and NTS, detectable at day 1 and persistently increased at every day examined in the PVS rats. However, the hyperdynamic circulation developed between days 3 to 5. Administration of c-fos antisense oligonucleotides eliminated the hyperdynamic circulation in PVS rats, but had no effect on sham-operated controls. We conclude that the activation of central cardiovascular-regulatory nuclei, through a c-fos-dependent pathway, is necessary for development of hyperdynamic circulation in portal-hypertensive rats. PMID- 11786973 TI - Decreases in portal flow trigger a hepatorenal reflex to inhibit renal sodium and water excretion in rats: role of adenosine. AB - The regulation of renal sodium and water excretion through a hepatorenal reflex activated by the changes in hemodynamics of the portal circulation has been suggested. We hypothesize that the changes in intrahepatic blood flow and flow related intrahepatic adenosine are involved in the control of renal water and sodium excretion by triggering a hepatorenal reflex. Anesthetized rats were instrumented to monitor the systemic, hepatic, and renal circulation. A vascular shunt connecting the portal vein and central vena cava was established to allow for control of the portal venous blood flow (PVBF). Urine was collected from the bladder. The effects of decreased PVBF on renal water and sodium excretion were compared in normal and hepatic denervated rats. Decreasing intrahepatic PVBF by half for 30 minutes decreased urine flow by 38% (12.1 +/- 1.1 vs. 7.5 +/- 0.7 microL. min(-1)) and urine sodium excretion by 44% (1.11 +/- 0.30 vs. 0.62 +/- 0.17 micromol. min(-1)). Renal arterial blood flow (RABF) and creatinine clearance were also reduced by the decreases in intrahepatic PVBF. Hepatic denervation, or intrahepatic administration of an adenosine receptor antagonist, 8-phenyltheophylline (8-PT), abolished the effects of decreasing PVBF on urine flow and sodium excretion. The data suggest that the decrease in intrahepatic PVBF triggers a hepatorenal reflex through the activation of adenosine receptors within the liver, thereby inhibiting renal water and sodium excretion. The water and sodium retention commonly seen in the hepatorenal syndrome may be related to intrahepatic adenosine accumulation resulting from the associated decrease in intrahepatic portal flow. PMID- 11786974 TI - Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis. AB - Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 microg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 microg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers <10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV-related cirrhosis. PMID- 11786975 TI - Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. AB - Hepatologists are frequently asked to evaluate human immunodeficiency virus (HIV) infected patients with abnormal liver enzymes and to assess the causal role of medications, such as antiretroviral drugs. Recently, the use of HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine (NVP) and efavirenz (EFV), has been associated with severe hepatic injury. We prospectively studied the incidence of severe hepatotoxicity (grade 3 or 4 change in alanine or aspartate transaminase levels) among 568 patients receiving NNRTI containing antiretroviral therapy, including 312 and 256 patients prescribed EFV and NVP, respectively. Hepatitis C virus (HCV) and hepatitis B virus (HBV) were detected in 43% and 7.7% of patients, respectively. Severe hepatotoxicity was observed in 15.6% of patients prescribed NVP and 8.0% of those prescribed EFV, but only 32% of NVP and 50% of EFV-associated episodes were detected during the first 12-weeks of therapy. The risk was significantly greater among persons with chronic viral hepatitis (69% of cases) and those prescribed concurrent protease inhibitors (PIs) (82% of cases). Nonetheless, 84% of patients with chronic HCV or HBV did not experience severe hepatotoxicity. Severe hepatotoxicity occurs throughout the course of NNRTI therapy and is more common among patients prescribed nevirapine, those coinfected with HCV or HBV, and those coadministered protease inhibitors. PMID- 11786976 TI - Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: correlation with clinical disease stages. AB - Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, affecting approximately 2% of the world's population. The immune mechanisms responsible for the highly variable natural history in a given individual are unknown. We used a multiparameter flow cytometric technique to functionally and phenotypically characterize HCV-specific effector T cells in the peripheral blood of 32 individuals with different stages of hepatitis C disease (resolved, mild chronic, advanced chronic) and normal controls. We found the highest frequencies of virus specific effector cells with an activated memory phenotype (CD45RO+CD69+) in subjects who had resolved HCV infection, either spontaneously or with antiviral therapy. Effector cells from patients with resolved infection produced Th1 type cytokines following stimulation with nonstructural antigens (NS3 and NS4), whereas effector cells from chronically infected patients produced Th1 type cytokines predominantly following stimulation with the HCV core antigen. Stimulation with superantigen staphylococcal enterotoxin (SEB) induced the same levels of cytokine production in the different patient groups. Among the HCV seropositive patients, viral load inversely correlated with the Th1 effector cell response to NS3. Interleukin (IL)-4 was produced only in response to the control antigens, but not in response to the HCV recombinant proteins. Taken together, these findings suggest that a vigorous HCV-specific CD4+ Th1 response, particularly against the nonstructural proteins of the virus, may be associated with viral clearance and protection from disease progression. Prospective studies using this new flow cytometric assay will be required to determine whether antiviral therapy modifies the frequency, specificity, and function of these virus-specific effector cells. PMID- 11786977 TI - Inhibition of internal ribosomal entry site-directed translation of HCV by recombinant IFN-alpha correlates with a reduced La protein. AB - Translation of the hepatitis C virus (HCV) polyprotein is mediated by an internal ribosome entry site (IRES) that is located within the 5'-nontranslated region (5'NTR). We investigated the effect of interferon alfa (IFN-alpha) on the IRES directed translation of HCV, using two stably transformed cell lines, RCF-1 and RCF-26, of Huh7 cells derived from human hepatocellular carcinoma that express dicistronic reporter proteins, Renilla luciferase (RL) and firefly luciferase (FL), separated by HCV-IRES. After the administration of IFN-alpha or poly(I) poly(C), HCV-IRES-directed translation was inhibited in a dose-dependent manner. The relative HCV-IRES activity (F/L) decreased to 60% at 5,000 IU/mL of IFN-alpha and 45% at 40 microg/mL of poly(I)-poly(C). Thus, IFN-alpha or poly(I)-poly(C) inhibited HCV-IRES-directed translation more efficiently than a cellular cap dependent translation. 2',5'-oligoadenylate synthetase (2',5'AS) protein level in cells analyzed significantly increased after the administration of IFN-alpha, but not upon poly(I)-poly(C). Overexpression of double-stranded RNA-activated protein kinase (PKR) gene did not mimic the selective inhibition of HCV-IRES-directed translation in the transformant cells, suggesting that neither the 2',5'AS nor the PKR system are involved in this selective inhibition. Interestingly, the expression of the autoantigen, La, which has been reported to enhance HCV-IRES directed translation, was significantly reduced after the administration of IFN alpha and poly(I)-poly(C) in a dose-dependent manner. Transient expression of La protein completely restored the selective inhibition of HCV-IRES-directed translation by IFN-alpha and poly(I)-poly(C). These findings suggested a new antiviral mechanism induced by IFN-alpha in that IFN-alpha or poly(I)-poly(C) selectively inhibited HCV-IRES-directed translation compared with the eukaryotic cap-dependent translation through the reduction of La protein. PMID- 11786978 TI - Cis-preferential recruitment of duck hepatitis B virus core protein to the RNA/polymerase preassembly complex. AB - Hepadnaviral replication requires the concerted action of the polymerase and core proteins to ensure selective packaging of the RNA pregenome into nucleocapsids. Virus assembly is initiated by cis-preferential binding of polymerase to the encapsidation signal straightepsilon, present on pregenomic RNA. Using the duck hepatitis B virus (DHBV) model, we analyzed how core protein is recruited to the RNA/polymerase preassembly complex. Two sets of trans-complementation assays were performed in cotransfected hepatoma cells. First, a replication-competent DHBV construct was tested for its ability to rescue replication of genomes bearing mutations within the core region. Self-packaging of wild-type pregenomes was more efficient than cross-packaging of core-deficient pregenomes, and this bias was strongly enhanced if mutant pregenomes coded for self-assembly-competent, but packaging-deficient, core proteins. Second, the site of wild-type core protein translation, i.e., pregenomic RNA (cis) or separate messenger RNA (trans), was analyzed for its effect on the phenotype of a previously described dominant negative (DN) DHBV core protein mutant. This mutant forms chimeric nucleocapsids with wild-type core proteins and blocks reverse transcription within most, but not all, mixed particles. Strikingly, suppression of viral DNA synthesis by the mutant increased 100-fold when wild-type core protein was provided in trans. Our results suggest that recruitment of core protein to the DHBV preassembly complex occurs in a cis-preferential manner. This mechanism may account for the leakiness of DN DHBV core protein mutants targeting reverse transcription. PMID- 11786979 TI - Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly(ADP-ribosyl)ation. AB - Chronic infection with hepatitis B virus (HBV) is associated with an increased risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Although clonal HBV DNA integrations are detected in nearly all HCCs the role of these integrations in hepatocarcinogenesis is poorly understood. We have used a cloning protocol that allows studying the frequency and the natural history of HBV DNA integrations in cell culture. Southern blot analysis of the genomic DNA of HepG2 2.2.15 subclones, which replicate HBV, enabled us to detect new HBV DNA integrations in approximately 10% of the HepG 2.2.15 subclones over 4 rounds of sequential subcloning, whereas no loss of any preexisting HBV DNA integrations was observed. Treatments of HepG2 cells with H(2)O(2), designed to increase DNA damage, increased the frequency of HBV integrations to approximately 50% of the subclones and treatments designed to inhibit DNA repair, by inhibiting Poly(ADP ribosyl)ation, also increased the frequency of HBV integration to 50%. These findings suggest that DNA strand breaks induced by oxidative stress during persistent HBV infection in humans may increase HBV DNA integration events, whereas PARP-1 activity may function to limit the occurrence of de novo HBV DNA integrations. PMID- 11786980 TI - New therapeutic strategies for hepatitis C. PMID- 11786981 TI - Nuclear xeno-sensors as receptors for cholestatic bile acids: the second line of defense. PMID- 11786982 TI - Vaccination for hepatitis B after transplantation: a realistic goal? PMID- 11786984 TI - The 4,977-base pair common deletion of mitochondrial DNA is not associated with steatosis in chronic hepatitis C patients. PMID- 11786983 TI - Interleukin 2 treatment does not modify hepatitis B or C replication in human immunodeficiency virus-infected patients: results from a randomized control trial. PMID- 11786985 TI - HDL receptor SR-BI and cholesterol gallstones. PMID- 11786986 TI - Promoter polymorphism of the CD14 endotoxin receptor gene and primary biliary cirrhosis. PMID- 11786987 TI - Child comes of age. PMID- 11786989 TI - Human facial expressions as adaptations: Evolutionary questions in facial expression research. AB - The importance of the face in social interaction and social intelligence is widely recognized in anthropology. Yet the adaptive functions of human facial expression remain largely unknown. An evolutionary model of human facial expression as behavioral adaptation can be constructed, given the current knowledge of the phenotypic variation, ecological contexts, and fitness consequences of facial behavior. Studies of facial expression are available, but results are not typically framed in an evolutionary perspective. This review identifies the relevant physical phenomena of facial expression and integrates the study of this behavior with the anthropological study of communication and sociality in general. Anthropological issues with relevance to the evolutionary study of facial expression include: facial expressions as coordinated, stereotyped behavioral phenotypes, the unique contexts and functions of different facial expressions, the relationship of facial expression to speech, the value of facial expressions as signals, and the relationship of facial expression to social intelligence in humans and in nonhuman primates. Human smiling is used as an example of adaptation, and testable hypotheses concerning the human smile, as well as other expressions, are proposed. PMID- 11786990 TI - Sexual dimorphism in primate evolution. AB - Sexual dimorphism is a pervasive phenomenon among anthropoid primates. Comparative analyses over the past 30 years have greatly expanded our understanding of both variation in the expression of dimorphism among primates, and the underlying causes of sexual dimorphism. Dimorphism in body mass and canine tooth size is familiar, as is pelage and "sex skin" dimorphism. More recent analyses are documenting subtle differences in the pattern of skeletal dimorphism among primates. Comparative analyses have corroborated the sexual selection hypotheses, and have provided a more detailed understanding of the relationship between sexual selection, natural selection, and mating systems in primates. A clearer picture is emerging of the relative contribution of various selective and nonselective mechanisms in the evolution and expression of dimorphism. Most importantly, recent studies have shown that dimorphism is the product of changes in both male and female traits. Developmental studies demonstrate the variety of ontogenetic pathways that can lead to dimorphism, and provide additional insight into the selective mechanisms that influence dimorphism throughout the lifetime of an animal. Evidence from the fossil record suggests that dimorphism probably evolved in parallel twice, and the dimorphism in some extinct hominoids probably exceeded that of any living primate. Our advances in understanding the behavioral/ecological correlates of dimorphism in living primates have not improved our ability to reconstruct social systems in extinct species on the basis of dimorphism alone, beyond the inference of polygyny or intense male-male competition. However, our understanding of the behavioral/ecological correlates of growth and development, and of the expression of dimorphism as a function of separate changes in male and female traits, offers great potential for inferring evolutionary changes in behavior over time. PMID- 11786991 TI - Loss of N-glycolylneuraminic acid in humans: Mechanisms, consequences, and implications for hominid evolution. AB - The surface of all mammalian cells is covered with a dense and complex array of sugar chains, which are frequently terminated by members of a family of molecules called sialic acids. One particular sialic acid called N-glycolylneuraminic acid (Neu5Gc) is widely expressed on most mammalian tissues, but is not easily detectable on human cells. In fact, it provokes an immune response in adult humans. The human deficiency of Neu5Gc is explained by an inactivating mutation in the gene encoding CMP-N-acetylneuraminic acid hydroxylase, the rate-limiting enzyme in generating Neu5Gc in cells of other mammals. This deficiency also results in an excess of the precursor sialic acid N-acetylneuraminic acid (Neu5Ac) in humans. This mutation appears universal to modern humans, occurred sometime after our last common ancestor with the great apes, and happens to be one of the first known human-great ape genetic differences with an obvious biochemical readout. While the original selection mechanisms and major biological consequences of this human-specific mutation remain uncertain, several interesting clues are currently being pursued. First, there is evidence that the human condition can explain differences in susceptibility or resistance to certain microbial pathogens. Second, the functions of some endogenous receptors for sialic acids in the immune system may be altered by this difference. Third, despite the lack of any obvious alternate pathway for synthesis, Neu5Gc has been reported in human tumors and possibly in human fetal tissues, and traces have even been detected in normal human tissues. One possible explanation is that this represents accumulation of Neu5Gc from dietary sources of animal origin. Finally, a markedly reduced expression of hydroxylase in the brains of other mammals raises the possibility that the human-specific mutation of this enzyme could have played a role in human brain evolution. PMID- 11786992 TI - Origin of human bipedalism: The knuckle-walking hypothesis revisited. AB - Some of the most long-standing questions in paleoanthropology concern how and why human bipedalism evolved. Over the last century, many hypotheses have been offered on the mode of locomotion from which bipedalism originated. Candidate ancestral adaptations include monkey-like arboreal or terrestrial quadrupedalism, gibbon- or orangutan-like (or other forms of) climbing and suspension, and knuckle-walking. This paper reviews the history of these hypotheses, outlines their predictions, and assesses them in light of current phylogenetic, comparative anatomical, and fossil evidence. The functional significance of characteristics of the shoulder and arm, elbow, wrist, and hand shared by African apes and humans, including their fossil relatives, most strongly supports the knuckle-walking hypothesis, which reconstructs the ancestor as being adapted to knuckle-walking and arboreal climbing. Future fossil discoveries, and a clear understanding of anthropoid locomotor anatomy, are required to ultimately test these hypotheses. If knuckle-walking was an important component of the behavioral repertoire of the prebipedal human ancestor, then we can reject scenarios on the origin of bipedalism that rely on a strictly arboreal ancestor. Moreover, paleoenvironmental data associated with the earliest hominins, and their close relatives, contradict hypotheses that place the agents of selection for bipedality in open savanna habitats. Existing hypotheses must explain why bipedalism would evolve from an ancestor that was already partly terrestrial. Many food acquisition and carrying hypotheses remain tenable in light of current evidence. PMID- 11786993 TI - Paleohistopathology of bone: a new approach to the study of ancient diseases. AB - Light microscopy, particularly the use of polarized light, has such a high value for the differential diagnosis of dry bones that it can no longer be neglected. Alterations caused intra vitam by disease or other living conditions can clearly be differentiated by this technique from changes due to postmortem reactions (e.g., pseudopathology). As a reliable diagnosis is the basis not only of the study of case reports but also of the etiology and epidemiology of diseases in ancient populations, paleopathologists would be well-advised to employ histological analysis for their research, to avoid false diagnoses. The necessary basis for such research is the knowledge of the general histology, histogenesis, and growth as well as pathophysiology of bone. Some new techniques which facilitate the practical use of microscopic analysis, such as the preparation of thin-ground sections from undecalcified bone samples and nonrehydrated mummified soft tissues, are described. Selected examples of mechanisms of pathological bone changes, particularly the determination of vestiges of diseases in macerated bones by microscopy, are presented. Emphasis is placed on the differential diagnoses of proliferative reactions (e.g., periosteal processes of long bones and the skull). In this context, the importance of meningeal reactions on the endocranial lamina of the skull for morbidity and mortality in ancient populations is demonstrated. Furthermore, porotic hyperostosis of the skull vault and the orbital roof, i.e., the cribra cranii externa and cribra orbitalia, is discussed. Selected examples of the etiology and epidemiology of ancient diseases are presented (e.g., anemia, scurvy, rickets, and meningeal diseases), and ideas on living conditions and their implications for the origin and the spread of disease are given to establish a better understanding of deficiency and infectious diseases in the past. PMID- 11786994 TI - Reproductive ecology and life history of the human male. AB - Until recently, the reproductive ecology of human males has not been extensively investigated, primarily as a result of the need for a theoretical framework based on the reproductive constraints and energetics of mammalian males. More specifically, male reproductive ecology has necessitated an integrative interpretation of clinical and anthropological data based on the premise that the evolution of human male life histories has involved selection for physiological mechanisms aimed at optimizing trade-offs between survivorship and reproductive effort. This paper attempts to address this gap in our understanding by presenting the current state of male reproductive ecology, including physiologic data from clinical and anthropological investigations as well as recent theoretical developments. Recent investigations outlining population variation in reproductive endocrine function are discussed within the context of potential sources of variation, including energetic expediture, caloric intake, and developmental canalization during adolescence. Additional summaries of male senescence and behavior are presented to provide a complete overview of male life history. Implications of recent anthropological data on contemporary health issues such as prostate cancer and the development of a male contraceptive are also discussed. Finally, several theories are presented that may contribute to our understanding of the evolution of male life histories and reproductive ecology, including theoretical suggestions involving the role of competition, mate choosiness, and potential constraints on male insemination ability, as well as a theory suggesting that male reproductive ecology may be best understood by analyzing energetic allocation decisions between differing somatic tissues that may be indicative of the competing needs for optimizing survivorship and reproductive effort. Directions for future research are finally considered. PMID- 11786995 TI - A proper study for mankind: Analogies from the Papionin monkeys and their implications for human evolution. AB - This paper's theme is that analogies drawn from the cercopithecine tribe Papionini, especially the African subtribe Papionina (baboons, mangabeys, and mandrills), can be a valuable source of insights about the evolution of the human tribe, Hominini, to complement homologies found in extant humans and/or African apes. Analogies, involving a "likeness of relations" of the form "A is to B, as X is to Y," can be usefully derived from nonhomologous (homoplastic) resemblances in morphology, behavior, ecology, or population structure. Pragmatically, the papionins are a fruitful source of analogies for hominins because they are phylogenetically close enough to share many basic attributes by homology, yet far enough that homoplastic modifications of these features are easily recognized as such. In "The Seedeaters," an analogy between Theropithecus among baboons and Australopithecus africanus among hominines was the source of a widely discussed (and often misrepresented) diet-based scenario of hominin origins that explained previously unassociated hominin apomorphies, interpreted basal hominins as nonhuman rather than prehuman primates, and accommodated a basal hominin adaptive radiation of at least two lines. Current usage recognizes an even more extensive evolutionary radiation among the basal hominins, originating no earlier than about 7 ma, with multiple lineages documented or inferred by 2.5 ma. Although multilineage clades (especially the Paranthropus clade) within this complex are widely recognized, and emerge from sophisticated, parsimony-based analyses, it is suspected that in many cases, developmental or functional homoplasies are overwhelming the phylogenetic signal in the data. The papionin analogy (specifically the splitting of the traditional, morphology-based genera Cercocebus and Papio mandated by molecular evidence) illustrates the power of these factors to produce erroneous cladograms. Moreover, the rapid deployment of basal hominins across varied African habitats was an ideal scenario for producing morphologically undetectable homoplasy. There seems to be no foolproof way to distinguish, a priori, homologous from homoplastic resemblances in morphology, but one pragmatic strategy is to severely censor the datset, retaining only resemblances or differences (often apparently trivial ones) that cannot be reasonably explained on the basis of functional resemblance or difference, respectively. This strategy may eliminate most morpological data, and leave many fossil taxa incertae sedis, but this is preferable to unwarranted phylogenetic confidence. Another source of phylogenetic uncertainty is the possibility of gene flow by occasional hybridization between hominins belonging to ecologically and adaptively distinct species or even genera. Although the evidence is unsatisfactorily sparse, it suggests that among catarrhines generally, regardless of major chromosomal rearrangements, intersterility is roughly proportional to time since cladogenetic separation. On a papionin analogy, especially the crossability of Papio hamadryas with Macaca mulatta and Theropithecus gelada, crossing between extant hominine genera is unlikely to produce viable and fertile offspring, but any hominine species whose ancestries diverged less than 4 ma previously may well have been able to produce hybrid offspring that could, by backcrossing, introduce alien genes with the potential of spreading if advantageous. Selection against maladaptive traits would maintain adaptive complexes against occasional genetic infiltration, and the latter does not justify reducing the hybridizing forms to a conspecific or congeneric rank. Whether reticulation could explain apparent parallels in hominin dentition and brain size is uncertain, pending genetic investigation of these apparently complex traits. Widespread papionin taxa (such as Papio baboons and species groups of the genus Macaca), like many such organisms, are distributed as a "patchwork" of nonoverlapping but often parapatric forms (allotaxa). Morphologically diagnosable, yet not reproductively isolated, most allotaxa would be designated species by the phylogenetic species concept, but subspecies by the biological species concept, and use of the term "allotaxa" avoids this inconsistency. A line of contact between allotaxa typically coincides with an ecotone, with neighboring allotaxa occupying similar econiches in slightly different habitats, and often exhibiting subtle, adaptive, morphological differences as well as their defining differences of pelage. "Hybrid zones," with a wide variety of internal genetic structures and dynamics, typically separate parapatric allotaxa. Current models attribute the formation and maintenance of allotaxa to rapid pulses of population expansion and contraction to and from refugia, driven by late Neogene climatic fluctuations. An overall similarity in depth of genetic diversity suggests that papionin taxa such as Papio baboons, rather than extant humans, may present the better analogy for human population structure of the "prereplacement" era. Neandertals and Afro-Arabian "premodern" populations may have been analogous to extant baboon (and macaque) allotaxa: "phylogenetic" species, but "biological" subspecies. "Replacement," in Europe, probably involved a rapidly sweeping hybrid zone, driven by differential population pressure from the "modern" side. Since the genetic outcome of hybridization at allotaxon boundaries is so variable, the problem of whether any Neandertal genes survived the sweep, and subsequent genetic upheavals, is a purely empirical one; if any genes passed "upstream" across the moving zone, they are likely to be those conferring local adaptive advantage, and markers linked to these. In general, extant papionin analogies suggest that the dynamics and interrelationships among hominin populations now known only from fossils are likely to have been more complex than we are likely to be able to discern from the evidence available, and also more complex than can be easily expressed in conventional taxonomic terminology. PMID- 11786996 TI - Mode of action of recombinant Azotobacter vinelandii mannuronan C-5 epimerases AlgE2 and AlgE4. AB - The enzymes mannuronan C-5 epimerases catalyze conversion of beta-D-mannuronic acid to alpha-L-guluronic acid in alginates at the polymer level and thereby introduce sequences that have functional properties relevant to gelation. The enzymatic conversion by recombinant mannuronan C-5 epimerases AlgE4 and AlgE2 on alginate type substrates with different degree of polymerization and initial low fraction of alpha-L-guluronic acid was investigated. Essentially no enzymatic activity was found for fractionated mannuronan oligomer substrates with an average degree of polymerization, DP(n), less than or equal 6, whereas increasing the DP(n) yielded increased epimerization activity. This indicates that these enzymes have an active site consisting of binding domains for consecutive residues that requires interaction with 7 or more consecutive residues to show enzymatic activity. The experimentally determined kinetics of the reaction, and the residue sequence arrangement introduced by the epimerization, were modeled using Monte Carlo simulation accounting for the various competing intrachain substrates and assuming either a processive mode of action or preferred attack. The comparison between experimental data and simulation results suggests that epimerization by AlgE4 is best described by a processive mode of action, whereas the mode of action of AlgE2 appears to be more difficult to determine. PMID- 11786997 TI - Conformational studies of Lewis X and Lewis A trisaccharides using NMR residual dipolar couplings. AB - The conformations of the histo-blood group carbohydrate antigens Lewis X (Le(x)) and Lewis A (Le(a)) were studied by NMR measurements of one-bond C-H residual dipolar couplings in partially oriented liquid crystal solutions. A strategy for rapid calculation of the difference between theoretical and experimental dipolar couplings of a large number of model structures generated by computer simulations was developed, resulting in an accurate model structure for the compounds. Monte Carlo simulations were used to generate models for the trisaccharides, and orientations of each model were sought that could reproduce the experimental residual dipolar coupling values. For both, Le(a) and Le(x), single low energy models giving excellent agreement with experiment were found, implying a compact rigidly folded conformation for both trisaccharides. The new approach was also applied to the pentasaccharides lacto-N-fucopentaose 2 (LNF-2) and lacto-N fucopentaose 3 (LNF-3) proving its consistency and robustness. For describing the conformation of tightly folded oligosaccharides, a definition for characterization of ring planes in pyranoside chairs is proposed and applied to the analysis of the relation between the fucose and galactose residues in the epitopes, revealing the structural similarity between them. PMID- 11786998 TI - Molecular dynamics calculations on amylose fragments. I. Glass transition temperatures of maltodecaose at 1, 5, 10, and 15.8% hydration. AB - Molecular dynamics simulations (NPT ensembles, 1 atm) using the all atom force field AMB99C (F. A. Momany and J. L. Willett, Carbohydrate Research, Vol. 326, pp 194-209 and 210-226), are applied to a periodic cell containing ten maltodecaose fragments and TIP3P water molecules. Simulations were carried out at 25 K intervals over a range of temperatures above and below the expected glass transition temperature, T(g), for different water concentrations. The amorphous cell was constructed through successive dynamic equilibration steps at temperatures above T(g) and the temperature lowered until several points of reduced slope (1/T vs volume) were obtained. This procedure was carried out at each hydration level. Each dynamics simulation was continued until the volume remained constant without up or down drift for at least the last 100 ps. For a given temperature, most simulations required 400-600 ps to reach an equilibrium state, but longer times were necessary as the amount of water in the cell was reduced. A total of more than 30 ns of simulations were required for the complete study. The T(g) for each hydrated cell was taken as that point at which a discontinuity in slope of the volume (V), potential energy (PE), or density (rho) vs 1/T was observed. The average calculated T(g) values were 311, 337, 386, and 477 K for hydration levels of 15.8, 10, 5, and 1%, respectively, in generally good agreement with experimental values. The T(g) for anhydrous amylose is above the decomposition temperature for carbohydrates and so cannot be easily measured. However, it has also been difficult to obtain a value of T(g) for anhydrous amylose using simulation methods. Other molecular parameters such as end-to-end distances, mean square distributions, and pair distributions are discussed. PMID- 11786999 TI - NMR solution structure of the isolated Apo Pin1 WW domain: comparison to the x ray crystal structures of Pin1. AB - The NMR solution structure of the isolated Apo Pin1 WW domain (6-39) reveals that it adopts a twisted three-stranded antiparallel beta-sheet conformation, very similar to the structure exhibited by the crystal of this domain in the context of the two domain Pin1 protein. While the B factors in the apo x-ray crystal structure indicate that loop 1 and loop 2 are conformationally well defined, the solution NMR data suggest that loop 1 is quite flexible, at least in the absence of the ligand. The NMR chemical shift and nuclear Overhauser effect pattern exhibited by the 6-39 Pin1 WW domain has proven to be diagnostic for demonstrating that single site variants of this domain adopt a normally folded structure. Knowledge of this type is critical before embarking on time-consuming kinetic and thermodynamic studies required for a detailed understanding of beta sheet folding. PMID- 11787000 TI - Dynamics and orientation of transmembrane peptide from bacteriorhodopsin incorporated into lipid bilayer as revealed by solid state (31)P and (13)C NMR spectroscopy. AB - 13C and (31)P NMR spectra of a transmembrane peptide, [1-(13)C]Ala(14)-labeled A(6-34), of bacteriorhodopsin incorporated into dimyristoylphosphatidylcholine (DMPC) bilayer were recorded to clarify its dynamics and orientation in the lipid bilayer. This peptide is shown to take an alpha-helical form both in liquid crystalline and gel phases, as viewed from the conformation dependent (13)C chemical shifts. In addition, this peptide undergoes rapid rigid-body rotation about the helical axis at ambient temperature as viewed from the axially symmetric (13)C chemical shift anisotropy, whereas this symmetric anisotropy is changed to an asymmetric pattern at temperatures below 10 degrees C. We further incorporated the peptide into the spontaneously aligned DMPC bilayer to applied magnetic field, induced by dynorphin (dynorphin:DMPC =1:10), a heptadeca-opioid peptide with very high affinity to opioid receptor, in order to gain insight into its orientation in the bilayer. This magnetically aligned system turned out to be persistent even at 0 degrees C as viewed from (31)P NMR spectra of the lipid bilayer, after this peptide was incorporated into this system [A(6-34): dynorphin: DMPC = 4:10:100]. It was found from the (13)C NMR spectra of [1 (13)C]Ala(14) A(6-34) that the helical axis of A(6-34) is oriented parallel to the bilayer normal irrespective of the presence or absence of reorientation motion about the helical axis at a temperature above the lowered gel to liquid crystalline phase transition. PMID- 11787001 TI - Generalized concentration dependence of globular protein self-diffusion coefficients in aqueous solutions. AB - The self-diffusion coefficients of globular proteins (myoglobin, bovine serum albumin, barstar, lysozyme) in aqueous solutions at different temperatures and pH values are obtained by pulsed-gradient spin-echo NMR, and their concentration dependence is analyzed. The generalized concentration dependence of globular protein self-diffusion coefficients is empirically established, and compared to the concentration dependence of diffusion coefficients of flexible polymers and rigid Brownian particles. PMID- 11787002 TI - An optimized solid phase synthesis strategy--including on-resin lactamization--of astressin, its retro-, inverso-, and retro-inverso isomers as corticotropin releasing factor antagonists. AB - This report describes an optimized solid phase synthesis strategy for astressin and new derivatives thereof. The synthesis is based on 9 fluorenylmethyloxycarbonyl/allyl/tert-butyl chemistry. The glutamic acid and lysine residue, which together form the cyclic constraint by coupling of their side chains, were protected by allyl functionalities during the synthesis of the linear peptide. Allyl removal by Pd(0) and the construction of the lactam bridge have been performed on-resin after completion of the chain assembly. This synthetic methodology resulted in high chemical yields (58-72%) and excellent purities of the crude peptides. The peptides were tested for their binding at the corticotropin releasing factor receptor, type 1, and their corticotropin releasing factor antagonistic activity. Furthermore, astressin and its analogs were studied by CD in order to determine the secondary structure in solution. Since the linear form of astressin and also the cyclic inverso isomer were found to be fully inactive, it can be concluded that a cyclic constraint and a right handed alpha-helix, respectively, are of utmost importance for these peptides to act as corticotropin releasing factor antagonists. PMID- 11787003 TI - A molecular dynamics study of the stoichiometric complex formed by poly (alpha, L glutamate) and octyltrimethylammonium ions in chloroform solution. AB - We present a molecular dynamics simulation at 300 K in explicit solvent environment of chloroform of the stoichiometric complex formed by poly(alpha,L glutamate) and octyltrimethylammonium ions. We observed that the alpha-helix conformation of the polypeptide chain remains stable during a 2-ns run. The surfactant ions predominantly adopted an extended conformation that is stabilized by favorable interactions with the organic solvent. Analysis of the organization of the surfactant with respect to the polypeptide chain indicated that each octyltrimethylammonium cation was preferentially bound to more than one carboxylate group. It was found that the most populated arrangement was that with the surfactant cations interacting with two carboxylate groups simultaneously. PMID- 11787004 TI - Hydrodynamic properties of rigid macromolecules composed of ellipsoidal and cylindrical subunits. AB - A procedure is devised for the calculation of hydrodynamic properties of rigid macromolecules composed subunits that are modeled as ellipsoids of revolution and cylinders. Owing to the axial symmetry of these shapes, smooth shell models can be constructured for the subunit structure. The bead shell model so constructed is employed for the calculation of the properties. A computer program, HYDROSUB, has been written implementing both the model building and the hydrodynamic calculation. A detailed example of the use of this methodology is presented for the case of the solution properties of the human antibody molecule immunoglobulin G3 (IgG3). Finally, hints are given on other uses and applications of the procedure. PMID- 11787005 TI - Molecular dynamics simulations of alpha2 --> 8-linked disialoside: conformational analysis and implications for binding to proteins. AB - Computational methods have played a key role in elucidating the various three dimensional structures of oligosaccharides. Such structural information, together with other experimental data, leads to a better understanding of the role of oligosaccharide in various biological processes. The disialoside Neu5Ac-alpha2- >8-Neu5Ac appears as the terminal glycan in glycoproteins and glycolipids, and is known to play an important role in various events of cellular communication. Neurotoxins such as botulinum and tetanus require Neu5Ac-alpha2 --> 8-Neu5Ac for infecting the host. Glycoconjugates containing this disialoside and the enzymes catalyzing their biosynthesis are also regulated during cell growth, development, and differentiation. Unlike other biologically relevant disaccharides that have only two linkage bonds, the alpha2-->8-linked disialoside has four: C2-O, O-C8', C8'-C7', and C7'-C6'. The present report describes the results from nine 1 ns MD simulations of alpha2-->8-linked disialoside (Neu5Ac-alpha2-->8-Neu5Ac); simulations were run using GROMOS96 by explicitly considering the solvent molecules. Conformations around the O-C8' bond are restricted to the +sc/+ap regions due to stereochemical reasons. In contrast, conformations around the C2-O and C8'-C7' bonds were found to be largely unrestricted and all the three staggered regions are accessible. The conformations around the C7'-C6' bond were found to be in either the -sc or the anti region. These results are in excellent agreement with the available NMR and potential energy calculation studies. Overall, the disaccharide is flexible and adopts mainly two ensembles of conformations differing in the conformation around the C7'-C6' bond. The flexibility associated with this disaccharide allows for better optimization of intermolecular contacts while binding to proteins and this may partially compensate for the loss of conformational entropy that may be incurred due to disaccharide's flexibility. PMID- 11787006 TI - Temperature dependence of the Raman spectrum of DNA. II. Raman signatures of premelting and melting transitions of poly(dA).poly(dT) and comparison with poly(dA-dT).poly(dA-dT). AB - The temperature dependence of the Raman spectrum of poly(dA).poly(dT) (dA: deoxyadenosine; dT: thymidine), a model for DNA containing consecutive adenine.thymine (A.T) pairs, has been analyzed using a spectrometer of high spectral precision and sensitivity. Three temperature intervals are distinguished: (a) premelting (10 < t < 70 degrees C), in which the native double helix is structurally altered but not dissociated into single strands; (b) melting (70 < t < 80 degrees C), in which the duplex is dissociated into single strands; and (c) postmelting (80 < t degrees C), in which no significant structural change can be detected. The distinctive Raman difference signatures observed between 10 and 70 degrees C and between 70 and 80 degrees C are interpreted in terms of the structural changes specific to premelting and melting transitions, respectively. Premelting alters the low-temperature conformation of the deoxyribose-phosphate backbone and eliminates base hydrogen bonding that is distinct from canonical Watson-Crick hydrogen bonding; these premelting perturbations occur without disruption of base stacking. Conversely, melting eliminates canonical Watson-Crick pairing and base stacking. The results are compared with those reported previously on poly(dA-dT).poly(dA-dT), the DNA structure consisting of alternating A.T and T.A pairs (L. Movileanu, J. M. Benevides, and G. J. Thomas, Jr. Journal of Raman Spectroscopy, 1999, Vol. 30, pp. 637-649). Poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) exhibit strikingly dissimilar temperature-dependent Raman profiles prior to the onset of melting. However, the two duplexes exhibit very similar melting transitions, including the same Raman indicators of ruptured Watson-Crick pairing, base unstacking and collapse of backbone order. A detailed analysis of the data provides a comprehensive Raman assignment scheme for adenosine and thymidine residues of B DNA, delineates Raman markers diagnostic of consecutive A.T and alternating A.T/T.A tracts of DNA, and identifies the distinct Raman difference signatures for premelting and melting transitions in the two types of sequences. PMID- 11787007 TI - On residues in the disallowed region of the Ramachandran map. AB - An analysis of the occurrence of nonglycyl residues in conformations disallowed in the Ramachandran plot is presented. Ser, Asn, Thr, and Cys have the highest propensities to exhibit such conformations, and the branched aliphatic residues the lowest. Residues cluster in five regions and there are some trends in the types of residues and their side-chain conformations (chi(1)) occupying these. Majority of the residues are found at the edge of helices and strands and in short loops, and are involved in different types of weak, stabilizing interactions. A structural motif has been identified where a residue in disallowed conformation occurs as the first residue of a short 3(10)-helix. On the basis of the types of neighboring residues, the location in the three dimensional structure and accessibility, there are similarities with the occurrence of cis peptide bonds in protein structures. PMID- 11787008 TI - Recognizing shorter coding regions of human genes based on the statistics of stop codons. AB - With the quick progress of the Human Genome Project, a great amount of uncharacterized DNA sequences needs to be annotated copiously by better algorithms. Recognizing shorter coding sequences of human genes is one of the most important problems in gene recognition, which is not yet completely solved. This paper is devoted to solving the issue using a new method. The distributions of the three stop codons, i.e., TAA, TAG and TGA, in three phases along coding, noncoding, and intergenic sequences are studied in detail. Using the obtained distributions and other coding measures, a new algorithm for the recognition of shorter coding sequences of human genes is developed. The accuracy of the algorithm is tested based on a larger database of human genes. It is found that the average accuracy achieved is as high as 92.1% for the sequences with length of 192 base pairs, which is confirmed by sixfold cross-validation tests. It is hoped that by incorporating the present method with some existing algorithms, the accuracy for identifying human genes from unannotated sequences would be increased. PMID- 11787009 TI - Effects of osmoprotectant compounds on NCAM polysialylation under hyperosmotic stress and elevated pCO(2). AB - Elevated osmolality and pCO(2) have been shown to alter sialylation in a protein specific manner. In Chinese hamster ovary (CHO)MT2-l-8 cells, tPA sialylation changed only slightly from 40 to 250 mm Hg pCO(2), whereas neural cell adhesion molecule polysialic acid (NCAM PSA) content decreased by up to 70% at 250 mm Hg pCO(2), pH 7.2. NCAM PSA content also decreased with increasing NaCl or NH(4)Cl concentration. This suggests that PSA content is a sensitive indicator of conditions that may alter glycosylation. Amino acids and their derivatives have been used to protect hybridoma and CHO cell growth under hyperosmotic stress. We examined the impact of osmoprotectants on NCAM PSA content in CHO MT2-1-8 cells under hyperosmolality (up to 545 mOsm/kg) and at 195 and 250 mm Hg pCO(2). NCAM PSA content at 545 mOsm/kg was at least two-fold greater in the presence of glycine betaine or L-proline compared to that without osmoprotectant. Surprisingly, in the presence of 20 mM glycine betaine, PSA levels were 50-60% of the control level for osmolalities ranging from 320 to 545 mOsm/kg. Thus, glycine betaine inhibits NCAM polysialylation at osmolalities below 435 mOsm/kg and is beneficial at higher osmolalities. In contrast to glycine betaine, L-proline increased PSA content by 25-120% relative to the unprotected culture at < or =545 mOsm/kg. The decrease in NCAM PSA levels of CHO MT2-1-8 cells cultured at 195 mm Hg pCO(2)-435 mOsm/kg was not mitigated by the presence of 25 mM glycine betaine, glycine, or L-threonine, even though all of these compounds enhanced cell growth. At 250 mm Hg pCO(2), all osmoprotectants tested (20 mM L-threonine, L-proline, glycine, or glycine betaine) increased NCAM polysialylation, with 20 mM glycine betaine restoring NCAM PSA to near control levels. Thus, osmoprotectants may (partially) offset changes in glycosylation, as well as the inhibition of growth, in cells under environmental stress. Supernatant beta-galactosidase levels, which increase upon alkalization of acidic organelles, did not differ significantly under elevated pCO(2) and hyperosmolality from that at control conditions. PMID- 11787010 TI - Characterization of hybridoma cell responses to elevated pCO(2) and osmolality: intracellular pH, cell size, apoptosis, and metabolism. AB - CO(2) partial pressure (pCO(2)) in industrial cell culture reactors may reach 150 200 mm Hg, which can significantly inhibit cell growth and recombinant protein production. The inhibitory effects of elevated pCO(2) at constant pH are due to a combination of the increases in pCO(2) and [HCO(-) (3)], per se, and the associated increase in osmolality. To decouple the effects of pCO(2) and osmolality, low-salt basal media have been used to compensate for this associated increase in osmolality. Under control conditions (40 mm Hg-320 mOsm/kg), hybridoma cell growth and metabolism was similar in DMEM:F12 with 2% fetal bovine serum and serum-free HB GRO. In both media, pCO(2) and osmolality made dose dependent contributions to the inhibition of hybridoma cell growth and synergized to more extensively inhibit growth when combined. Elevated osmolality was associated with increased apoptosis. In contrast, elevated pCO(2) did not increase apoptotic cell death. Specific antibody production also increased with osmolality although not with pCO(2). In an effort to understand the mechanisms through which elevated pCO(2) and osmolality affect hybridoma cells, glucose metabolism, glutamine metabolism, intracellular pH (pHi), and cell size were monitored in batch cultures. Elevated pCO(2) (with or without osmolality compensation) inhibited glycolysis in a dose-dependent fashion in both media. Osmolality had little effect on glycolysis. On the other hand, elevated pCO(2) alone had no effect on glutamine metabolism, whereas elevated osmolality increased glutamine uptake. Hybridoma mean pHi was approximately 0.2 pH units lower than control at 140 mm Hg pCO(2) (with or without osmolality compensation) but further increases in pCO(2) did not further decrease pHi. Osmolality had little effect on pHi. Cell size was smaller than control at elevated pCO(2) at 320 mOsm/kg, and greater than control in hyperosmotic conditions at 40 mm Hg. PMID- 11787011 TI - Validation of a model for process development and scale-up of packed-bed solid state bioreactors. AB - We have validated our previously described model for scale-up of packed-bed solid state fermenters (Weber et al., 1999) with experiments in an adiabatic 15-dm(3) packed-bed reactor, using the fungi Coniothyrium minitans and Aspergillus oryzae. Effects of temperature on respiration, growth, and sporulation of the biocontrol fungus C. minitans on hemp impregnated with a liquid medium were determined in independent experiments, and the first two effects were translated into a kinetic model, which was incorporated in the material and energy balances of the packed bed model. Predicted temperatures corresponded well with experimental results. As predicted, large amounts of water were lost due to evaporative cooling. With hemp as support no shrinkage was observed, and temperatures could be adequately controlled, both with C. minitans and A. oryzae. In experiments with grains, strong shrinkage of the grains was expected and observed. Nevertheless, cultivation of C. minitans on oats succeeded because this fungus did not form a tight hyphal network between the grains. However, cultivation of A. oryzae failed because shrinkage combined with the strong hyphal network formed by this fungus resulted in channeling, local overheating of the bed, and very inhomogeneous growth of the fungus. For cultivation of C. minitans on oats and for cultivation of A. oryzae on wheat and hemp, no kinetic models were available. Nevertheless, the enthalpy and water balances gave accurate temperature predictions when online measurements of oxygen consumption were used as input. The current model can be improved by incorporation of (1) gas-solids water and heat transfer kinetics to account for deviations from equilibrium observed with fast-growing fungi such as A. oryzae, and (2) the dynamic response of the fungus to changes in temperature, which were neglected in the isothermal kinetic experiments. PMID- 11787012 TI - Development of an ultrahigh-temperature process for the enzymatic hydrolysis of lactose. III. Utilization of two thermostable beta-glycosidases in a continuous ultrafiltration membrane reactor and galacto-oligosaccharide formation under steady-state conditions. AB - Hydrolysis of lactose by hyperthermophilic beta-glycosidases from the archaea Sulfolobus solfataricus (SsbetaGly) and Pyrococcus furiosus (CelB) was carried out at 70 degrees C in a continuous stirred-tank reactor (CSTR) coupled to a 10 kDa cross-flow ultrafiltration module to recycle the enzyme. Recirculation rates of > or =1 min(-1), reaction of proteins with reducing sugars, and enzyme adsorption onto the membrane are major "operational" factors of enzyme inactivation in the CSTR. They cause the half-life times of SsbetaGly and CelB to be reduced two- and eight-fold, respectively, the average value for both enzymes now being approximately 5 to 7 days. Using lactose at initial concentrations of 45 and 170 g/L, the CSTR was operated at a constant conversion level of approximately 80% for more than 2 weeks without the occurrence of microbial contamination. The productivities for the SsbetaGly-catalyzed conversion of lactose were determined at different dilution rates and initial substrate concentrations, and exceed by a factor of < or =2 those observed with CelB under otherwise identical conditions. This difference reflects the approximately eight fold stronger product inhibition of CelB by D-glucose. While the maximum total galacto-oligosaccharide production (90-100 mM) at 170 g/L lactose in the CSTR was not different from that in the batch reactor (CelB) or was greater by approximately 25% (SsbetaGly), continuous and batchwise reactions with both enzymes differed markedly with regard to relative proportions of the individual saccharide components present at 80% substrate conversion. The CSTR yielded an up to four-fold greater ratio of disaccharides to trisaccharides concomitant with a 5- to 30-fold larger relative proportion of beta-D-Galp-(1-->3)-D-Glc in the product mixture. The results show that apart from continuous hydrolysis of lactose at 70 degrees C, a CSTR charged with SsbetaGly or CelB and operated at steady-state conditions could be a useful reaction system for the production of galacto-oligosaccharides in which composition is narrower and more easily programmable, in terms of the individual components contained, as compared to the batchwise reaction. PMID- 11787013 TI - An experimental and theoretical study on the dissolution of mural fibrin clots by tissue-type plasminogen activator. AB - During thrombolytic therapy and after recanalization is achieved, reduction in the volume of mural thrombi is desirable. Mural thrombi are known to contribute to rethrombosis and reocclusion. The lysis rate of mural thrombi has been demonstrated to increase with fluid flow in different experimental models, but the mechanisms responsible are unknown. An experimental and a theoretical study were developed to determine the contribution of outer convective transport to the lysis of mural fibrin clots. Normal human plasma containing recombinant tissue type plasminogen activator (tPA; 0.5 microg/mL) was (re)perfused over mural fibrin clots with fluorescently labeled fibrin at low arterial, arterial, or higher wall shear stresses (4, 18, or 41 dyn/cm(2), respectively) and lysis was monitored in real time. Flow accelerated lysis, but significantly only at the highest shear stress: The average lysis front velocity was 3 x 10(-5) cm/s at 41 dyn/cm(2) vs. almost half of that at the lower shear stresses. Confocal microscopy showed fibrin fibers dissolving only in a narrow region close to the surface when permeation velocity was predicted to be low. A heterogeneous transport-reaction finite element model was used to describe mural fibrinolysis. After scaling the effects of outer and inner convection, inner diffusion, and chemical reactions, a simplified inner diffusion/reaction model was used. Correlation to fibrin lysis data in purified systems dictated higher rates of plasmin(ogen) and tPA adsorption onto fibrin and a decreased catalytic rate of plasmin-mediated fibrin degradation, compared with published parameters. At each shear stress, the model predicted a temporal pattern of lysis of mural fibrin (similar to that observed experimentally), and protease accumulation in a narrow fibrin region and significant lysis inhibition by plasma alpha(2)-antiplasmin (according to the literature). Increasing outer convection accelerated mural fibrinolysis, but the model did not predict the big increase in lysis rate at the highest shear stress. At higher than arterial flows, additional mechanisms not accounted for in the current model, such as fibrin collapse at the fibrin front, may regulate the lysis of mural clots and determine the outcome of thrombolytic therapy. PMID- 11787014 TI - Hybrid model building methodology using unsupervised fuzzy clustering and supervised neural networks. AB - This paper suggests a model building methodology for dealing with new processes. The methodology, called Hybrid Fuzzy Neural Networks (HFNN), combines unsupervised fuzzy clustering and supervised neural networks in order to create simple and flexible models. Fuzzy clustering was used to define relevant domains on the input space. Then, sets of multilayer perceptrons (MLP) were trained (one for each domain) to map input-output relations, creating, in the process, a set of specified sub-models. The estimated output of the model was obtained by fusing the different sub-model outputs weighted by their predicted possibilities. On line reinforcement learning enabled improvement of the model. The determination of the optimal number of clusters is fundamental to the success of the HFNN approach. The effectiveness of several validity measures was compared to the generalization capability of the model and information criteria. The validity measures were tested with fermentation simulations and real fermentations of a yeast-like fungus, Aureobasidium pullulans. The results outline the criteria limitations. The learning capability of the HFNN was tested with the fermentation data. The results underline the advantages of HFNN over a single neural network. PMID- 11787015 TI - Generating favorable nano-environments for thermal and solvent stabilization of immobilized beta-galactosidase. AB - beta-Galactosidase (Escherichia coli) was immobilized through its thiol groups on thiolsulfinate-agarose gel. After enzyme immobilization, different nano environments were generated by reacting the excess of gel-bound thiolsulfinate moieties with 2-mercaptoethanesulfonic acid (S-gel), glutathione (G-gel), cysteamine (C-gel), and mercaptoethanol (M-gel). Concerning thermal stability at 50 degrees C, the G-gel and the M-gel derivatives were the most stable with residual activity values of 67% and 45%, respectively. The stability in several solvent systems was studied: ethyl acetate (1.6% vol/vol), ethylene glycol (50% vol/vol), and 2-propanol (50% vol/vol). In ethyl acetate, both the M-gel and S gel were highly stabilized; the time required for activity to decay to 80% of the initial activity was increased 29-fold for the M-gel and 20-fold for the S-gel with respect to the soluble enzyme. The G-gel was the least stable of all the derivatives. The different behaviors of the derivatives in thermal and solvent stability studies suggest that each nano-environment contributes differently to the enzyme stability, depending on the denaturing conditions. Therefore, it may be possible to tailor the matrix surface to maximize enzyme stability in particular applications. PMID- 11787016 TI - Effect of operating variables on the yield of recombinant trypsinogen for a pulse fed dilution-refolding reactor. AB - The inclusion body process route for manufacturing proteins offers distinct process advantages in terms of expression levels and the ease of initial inclusion body recovery. The efficiency of the refolding unit operation, however, does determine the overall economic feasibility of a process. Dilution refolding is the simplest and most extensively used refolding operation, although significant yield losses often occur due mainly to aggregation. Operating variables may have a significant effect on the degree of aggregation, but a systematic study has not been reported. This study investigates the effect of operating variables on the dilution refolding of solubilized r-trypsinogen inclusion bodies in a pulse-fed stirred reactor. Variables investigated were inclusion body washing, stirring speed, feed rate, concentration of solubilized r trypsinogen, and concentration of urea during solubilization of the inclusion bodies. Additionally, the effect of baffles in the reactor was investigated. The yield of renatured r-trypsinogen varied between 12 +/- 0.2% and 21 +/- 1.0% depending on the specific combination of operating variables employed. It is clear that a suboptimal operating strategy can significantly reduce protein yield. In particular, we note that an increased intensity of mixing adversely affected yield in contrast to previous reports indicating that enhanced dispersion increases yield. We conclude that yield is determined not only by the efficiency of dispersion, but also by the local chemical environment of the protein as it folds, and the rate of change of this environment. This will be controlled by micromixing effects, and hence the intensity of agitation, in a complex manner requiring further characterization. PMID- 11787017 TI - Continuous isolation of plasmid DNA by annular chromatography. AB - Continuous chromatographic separations, especially of multicomponent mixtures, constitute interesting options for biotechnological downstream processing. Taking the separation of plasmid DNA from clearified lysates on hydroxyapatite as a pertinent example, we discuss the potential of continuous annular chromatography (CAC) in comparison with conventional (preparative) batch chromatography. In CAC the column is realized in the form of a thin (5 mm, height 210 mm) slowly rotating annulus. The performance of such a CAC column is compared to that of an ("analytical") batch column of similar thickness (diameter) and length (4 x 250 mm) and that of a ("preparative") batch column of similar cross-sectional surface area and height (50 x 210 mm). The quality of the obtained plasmid as defined by the appearance of the corresponding agarose gels (native and linearized plasmid), the 260/280 ratio and the biological activity (transient transfection of HEK 293 cells) was found to be identical in all three cases. The yields are also shown to be equivalent. The loading factor is found to be the most decisive parameter for the transfer of a given separation method between the continuous and the batch columns. Under nonoptimized conditions, plate numbers tended to be lower in the continuous compared to the batch columns. This is shown to be largely due to an artifact created by the CAC design (collection of averaged fractions at the outlets) and can be overcome by optimizing the rotation speed. Surprisingly the large batch column consistently gave better plate numbers than either the small batch or the CAC column. Compared to the preparative batch column, wall effects are more pronounced in the CAC (respectively the small diameter batch column), which may translate into better bed stability but conceivably also contributes to an increase in plate height, due to the reduction in bed density usually observed in the proximity of the wall. The CAC is shown to be a powerful approach to continuous chromatography, which allows a direct and straightforward upscale of chromatographic bioseparation methods. PMID- 11787018 TI - Overexpression of alcohol dehydrogenase or pyruvate decarboxylase improves growth of hairy roots at reduced oxygen concentrations. AB - Overexpression of Arabidopsis thaliana genes for the fermentation enzymes, alcohol dehydrogenase and pyruvate decarboxylase, improved the tolerance of A. thaliana hairy roots to low oxygen conditions. Whereas the specific growth rate of untransformed hairy roots in shake flasks and in a multiple-tube recirculation bioreactor declined significantly with decreasing oxygen tension down to 25% air saturation, growth of the transformant root lines was maintained at rates similar to those achieved with full aeration. This work demonstrates that altering the expression of selected genes involved in anaerobic metabolism can alleviate the problems of oxygen deficiency in hairy root cultures caused by poor mixing and mass transfer conditions. PMID- 11787019 TI - Expression of functional mammalian P450 2E1 in hairy root cultures. AB - P450 2E1 is an important mammalian liver enzyme known to metabolize a wide range of compounds including several common environmental pollutants. The medicinal plant, Atropa belladonna, was transformed with Agrobacterium rhizogenes containing a binary vector with rabbit P450 2E1 in either the sense or antisense orientation. The resulting "hairy roots" were isolated and grown in liquid medium. Production of P450 2E1 protein was verified in the roots containing the 2E1 gene in the sense orientation. Transgenic and control root cultures were dosed with the environmental pollutant, trichloroethylene (TCE), and were analyzed for the TCE metabolites, chloral and trichloroethanol. The root cultures expressing the mammalian P450 2E1 had increased levels of the metabolites compared to the levels in the control roots. This method represents a quick way to screen transformants for expression of foreign genes before regeneration of whole plants, and also as a possible source of foreign protein for purification. PMID- 11787020 TI - Quantitative determination of cellulase concentration as distinct from cell concentration in studies of microbial cellulose utilization: analytical framework and methodological approach. AB - In analyzing microbial cellulose utilization, it would be useful to independently measure the mass concentration of cells and cellulase enzymes. Such measurements would allow investigation of the allocation of cellular resources between synthesis of cells and cellulase, in vivo cell- and cellulase-specific cellulose hydrolysis rates, and bioenergetics. Methodological protocols are not established for independent determination of cell and cellulase concentrations for the common case in which a substantial fraction of cellulase is attached to the cell surface. Alternative analytical approaches by which to develop such protocols are examined from the perspective of error minimization. For cell concentration measurement, acceptable accuracy is expected when the concentrations of a cell specific component (e.g., DNA) is determined or when total protein is determined in conjunction with a measurement specific to cellulase. For cellulase concentration measurement, acceptable accuracy is expected when a measurement specific to cellulase such as ELISA is used. Several analytical approaches are rejected based on large expected errors. PMID- 11787021 TI - Kinetics of baculovirus replication and release using real-time quantitative polymerase chain reaction. AB - The study of viral-based processes is hampered by (a) their complex, transient nature, (b) the instability of products, and (c) the lack of accurate diagnostic assays. Here, we describe the use of real-time quantitative polymerase chain reaction to characterize baculoviral infection. Baculovirus DNA content doubles every 1.7 h from 6 h post-infection until replication is halted at the onset of budding. No dynamic equilibrium exists between replication and release, and the kinetics are independent of the cell density at the time of infection. No more than 16% of the intracellular virus copies bud from the cell. PMID- 11787022 TI - Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. AB - Hydroxyapatite (HA) calcium phosphate cements (CPCs) are attractive materials for orthopedic applications because they can be molded into shape during implantation. However their low strength and brittle nature limits their potential applications to principally non-load-bearing applications. Little if any use has been made of the HA cement systems as manufacturing routes for preset HA bone grafts, which although not moldable pastes, are resorbable, unlike HA sintered ceramic. It is known that the strength of cements can be increased beyond that attainable from slurry systems by compaction, and this study investigates whether compaction significantly alters the specific surface area and pore-size distribution of CPC prepared according to the method of Brown and Chow. Compaction pressures of between 18 and 106 MPa were used to decrease the porosity from 50 to 31%, which resulted in an increase in the wet compressive strength from 4 to 37 MPa. The Weibull modulus was found to increase as porosity decreased; in addition the amount of porosity larger than the reactant particle size increased as porosity decreased. It is proposed that this was caused by a combination of voids created by the aqueous solvent used in fabrication and shrinkage that occurs on reaction. The specific surface area was unchanged by compaction. PMID- 11787023 TI - The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. AB - This randomized controlled blind prospective study is undertaken to evaluate the safety and efficacy of Seprafilm--a novel bioresorbable membrane of chemically modified hyaluronic acid and carboxymethylcellulose--in prevention and reduction of postoperative endometrial and endocervical synechiae formation after general suction evacuation or curettage for incomplete, missed, and recurrent abortion. In total, 150 patients with incomplete or missed abortion participated in the clinical study. The study population was divided into two main groups. In the treatment (Seprafilm) group (n=50), application of Seprafilm membrane in the endometrial cavity and the cervical canal was used after the suction evacuation and/or the curettage. In the control group (n=100), nothing was inserted in the uterus. Both groups were divided into two subgroups: patients who had no previous suction or curettage, (with no previous D&C) (n=88), and patients who had at least one previous suction or curettage (with one or more previous D&C) (n=62). In the treatment (Seprafilm) group, 32 patients had no previous D&C and 18 patients had one or more previous D&C. In the control group, 56 patients had no previous D&C and 44 patients had one or more previous D&C. Further fertility was estimated by pregnancy success in all groups. Endometrial synechiae formation was evaluated with the use of hysterosalpingography (HSG) in patients of all groups without pregnancy success 8 months after the intervention. Registering any adverse reaction and performing ultrasound controls assessed the safety of Seprafilm use. From the subgroup with no previous D&C, all 32 patients (100%) who received Seprafilm had a pregnancy in the following 8 months; in the controls, pregnancy occurred only in 54%. It was also demonstrated with hysterosalpingography (HSG) that patients with one or more previous interventions and no pregnancy 8 months later were adhesion free in 90% of the patients where Seprafilm was used, and only 50% in the untreated group. The membrane was tested on the endometrial area of the uterus and did not produce any adverse reaction. Ultrasound controls did not show any abnormal echoes. Intrauterine insertion of Seprafilm is safe, prevents the appearance of endocervical adhesions or endometrial synechiae after curettage, and reduces the area of the endometrial cavity occupied by them in a large percent of cases. It also seems that its use improves the possibility of a new pregnancy and fertility. PMID- 11787024 TI - Interlaboratory validation of oxidation-index measurement methods for UHMWPE after long-term shelf aging. AB - An international oxidation index standard would greatly benefit the orthopedic community by providing a universal scale for reporting oxidation data of ultra high molecular weight polyethylene (UHMWPE). We investigated whether severe oxidation associated with long-term shelf aging affects the repeatability and reproducibility of area-based oxidation index measurement techniques based on normalization with the use of 1370- or 2022-cm(-1) infrared (IR) absorption reference peaks. Because an oxidation index is expected to be independent of sample thickness, subsurface oxidation was examined with the use of both 100- and 200-microm-thick sections from tibial components (compression-molded GUR 1120, gamma irradiated in air) that were shelf aged for up to 11.5 years. Eight institutions in the United States and Europe participated in the present study, which was administered in accordance with ASTM E691. On average, the 100-microm thick samples were associated with significantly greater interlaboratory relative standard uncertainty (40.3%) when compared with the 200-microm samples (21.8%, p = 0.002). In contrast, the intralaboratory relative standard uncertainty was not significantly affected by the sample thickness (p = 0.21). The oxidation index method did not significantly influence either the interlaboratory or intralaboratory relative standard uncertainty (p = 0.32 or 0.75, respectively). Our interlaboratory data suggest that with the suitable choice of specimen thickness (e.g., 200 microm) and either of the two optimal oxidation index methods, interlaboratory reproducibility of the most heavily oxidized regions in long-term shelf-aged components can be quantified with a relative standard uncertainty of 21% or less. Therefore, both the 1370-cm(-1) and the 2022-cm(-1) reference peaks appear equally suitable for use in defining a standard method for calculating an oxidation index for UHMWPE. PMID- 11787025 TI - The effects of localized cold work on the heating characteristics of thermal therapy implants. AB - The use of cylindrical palladium-cobalt alloy rods has proven effective in the clinical ablation of prostate cancer. In order to thermally destroy tissue, the ferromagnetic implants must heat to temperatures greater than 42 degrees C and produce a power output of at least 400 mW. However, localized cold work such as bending may effect the heating characteristics of these rods and have detrimental clinical effect. Three different types of test devices were manufactured to introduce cold work at one point in the implant: a sharp bend, a curvature, and an MTS three-point bend. After bending, each rod was then restraightened. Rod power output before and after bending was measured by calorimetry. Statistical comparison of power output for prebent and restraightened rods versus degrees bent was performed through the use of the SAS MIXED procedure to fit a mixed model repeated-measures ANOVA with the use of multivariate models. In vitro testing showed that there was only a small change in the power output before and after rods were cold worked regardless of the type of bending. Therefore, localized cold work does not affect the clinical heating characteristics of rods. PMID- 11787026 TI - Collagen and bone viscoelasticity: a dynamic mechanical analysis. AB - The purpose of this study was to explore the effects of changes in Type I collagen on the viscoelasticity of bone. Bone coupons were heated at either 100 or 200 degrees C to induce the thermal denaturation of Type I collagen. Half of these specimens were rehydrated after heat treatment; the other half were tested in a dry condition. The degree of denatured collagen (DC%) was analyzed by a selective digestion technique with the use of alpha-chymotrypsin. Isothermal (37 degrees C) and variable temperature tests (scans from 35 to 200 degrees C) were performed with the use of a dynamic mechanical analyzer to evaluate changes in bone viscoelastic properties as a function of collagen damage, specifically, changes in the loss factor (tan delta) and storage modulus (E') were assessed. Significant collagen denaturation occurred only when bone was heated at 200 degrees C irrespective of the hydration condition. Also, DC% did not show a significant effect on tan delta. However, higher values of tan delta were observed in wet samples compared to dry specimens. The temperature-scan tests revealed that the hydration condition, but not DC%, significantly affected the behavior of tan delta. However, E' was not strongly influenced either by DC% or by water content. These results suggest that at a constant frequency the denaturation of collagen triple-helical molecules may have few effects on the viscoelasticity of bone, but moisture may play a prominent role in determining this property. PMID- 11787027 TI - Evaluation of a novel hemostatic device in an ovine parenchymal organ bleeding model of normal and impaired hemostasis. AB - Bleeding is a problem encountered by many surgeons, often complicated by the presence of coagulopathy or anticoagulant. The hemostatic effectiveness of CoStasis Surgical Hemostat (with bovine collagen, bovine thrombin, and autologous plasma) was evaluated and compared to a collagen sponge and to two investigational fibrin-sealant preparations under conditions of normal and impaired coagulation. A liver resection and controlled incisions in spleens and kidneys were made in sheep. Time to complete hemostasis and total blood loss were measured. Tissue response was evaluated at 7, 30, 60, and 75 days. CoStasis treated sites demonstrated significantly shorter time to hemostasis (all surgical sites combined) compared with fibrin sealant (investigational fibrin sealant 1) (p= .005) or collagen sponge (p=0.013). In anticoagulated animals, CoStasis and fibrin sealant (investigational fibrin sealant 2) had comparable mean times to hemostasis, and CoStasis-treated sites exhibited lowered average blood loss compared to investigational fibrin-sealant-2 treated sites. CoStasis-treated sites demonstrated higher levels of tissue repair (lower inflammation, more extensive tissue repair, and less residual implant) compared to fibrin-sealant- or collagen-sponge-treated sites in Phases I and II. These findings demonstrate that CoStasis is a highly effective hemostatic agent for control of bleeding from parenchymal organs. Furthermore, under conditions of compromised coagulation, treatment with CoStasis demonstrates a reduction in average blood loss when compared to treatment with fibrin sealant. PMID- 11787028 TI - Effect of sodium content on the crystallization behavior of fluoramphibole glass ceramics. AB - The purpose of this study was to evaluate the effect of sodium content on the crystallization behavior of glass-ceramics in the system SiO(2)-MgO-CaO-Na(2)O K(2)O-F. Five glass compositions were prepared with increasing sodium content. The compositions were melted at 1400 degrees C for 2 h and cast into 60 x 12-mm ingots. Differential thermal analyses were performed on the glasses up to 1400 degrees C. Discs (1.5 x 12 mm) were cut from the ingots, nucleated in the temperature range 600-650 degrees C for 1-2 h, and crystallized in the temperature range 900-1000 degrees C for 0.5-4 h. The crystalline phases were analyzed by x-ray diffraction. The microstructure was investigated by scanning electron microscopy. Differential thermal analyses showed that the crystallization exotherm occurred in the temperature range 600-750 degrees C. There was a linear relationship between the amount of sodium and the transformation temperatures. X-ray diffraction revealed the presence of mica and diopside as major crystalline phases in the sodium-free composition. Mica, diopside, and fluorrichterite were present in all other glass-ceramics. The microstructure of the sodium-free glass-ceramic was characterized by the presence of hexagonal mica crystals and prismatic diopside crystals. All other compositions exhibited needle-shaped fluorrichterite crystals (2-5 microm in length) in addition to mica and diopside crystals. PMID- 11787029 TI - Cytotoxicity of modern dentin adhesives--in vitro testing on gingival fibroblasts. AB - The present investigation was designed to test cellular toxicity of modern dentin adhesives. With the use of the products Ariston Liner, Etch & Prime 3.0, Optibond Solo, Prime & Bond NT, Scotchbond 1, and Syntac Sprint, test specimens were prepared according to the manufacturers' instructions and transferred into a culture medium. Eluates were obtained and pipetted onto fibroblast cultures, incubated, and subsequently stained. The respective cell densities and the numbers of normal, altered, and dead cells were determined and compared with control cell cultures. Statistical analysis of the data showed that all materials caused cytotoxic effects. Scotchbond 1 displayed the highest number of dead cells. The difference was statistically significant compared to Etch" 3.0, Optibond Solo, Prime&Bond NT, and the control. The lowest cell density was found for Scotchbond 1 and Ariston Liner. The difference was also statistically significant in comparison with Etch" 3.0, Optibond Solo, Prime&Bond NT, and the control. To conclude, all tested dentin adhesives caused cytotoxic reactions. Taking the limitations of an in vitro experiment into consideration, Prime&Bond NT, Optibond Solo, and Etch" 3.0 appear to be the most recommendable products, and Scotchbond 1 and Ariston Liner the least. PMID- 11787030 TI - Fixation strength of tapered versus bicylindrical hydroxyapatite-coated external fixation pins: an animal study. AB - The purpose of this study was to comparatively measure the bone-pin interface strength in two types of hydroxyapatite-coated pins that differed in shape, diameter, and implantation technique. Both pin types are commonly used for tibia fixation. Thirty bicylindrical 5/4-mm stainless-steel pins (Group A) and 30 tapered 6/5-mm stainless-steel pins (Group B) were implanted in the left tibiae of 10 adult sheep. A monolateral fixator was mounted on the pins after implantation. A 5-mm-long bone segment was removed from the tibial mid-diaphysis to ensure high load at the bone-pin interface. Pin insertion torque was 830 +/- 446 N/mm in Group A and 3415 +/- 743 N/mm in Group B (p<0.0001, one-way ANOVA). Six weeks after surgery, the sheep were euthanized and pin extraction torque measured. Pin extraction torque was 1237 +/- 499 N/mm in Group A and 3367 +/- 1512 N/mm in Group B (p<0.0001, Mann-Whitney test). Morphological analysis performed at 60x magnification showed a direct bone-pin contact in both groups. Despite challenging biomechanical conditions, this study showed both pin types to be well-fixed and osteointegrated. Therefore, both pin types are recommended for tibial fixation. However, the tapered pins showed higher extraction torque, an important result for external fixation treatments. PMID- 11787031 TI - A composite graft material containing bone particles and collagen in osteoinduction in mouse. AB - Demineralized allogenic bone matrices (DABM) and demineralized freeze-dried bone allograft (DFDBA) have been successfully used as bone-graft materials in the treatment of acquired and congenital cranio-maxillofacial defects and in some orthopedic surgery. However, these bone-graft "powders" have many shortcomings. For example, placement of particulate graft material in a hemorrhaging site can result in inadequacies or inaccurate attachment as well as loss of the graft materials. To minimize the inadequacies of powderlike graft materials, xenogenic collagen isolated from human tendon, skin, or bone was added to the bone-graft particles to form a composite spongelike implant. This material is commercially available and consists of 60% collagen and 40% DFDBA (DynaGraft, GenSci Co., Irvine, CA). The goal of this study was to evaluate the characteristics of composite graft implants in the mineralization process in an animal model in comparison with DFDBA powder and pure collagen. Seventy-two Swiss Webster mice were divided into three groups: an experimental group implanted with DynaGraft, two comparison groups implanted with either DFDBA or collagen only. All the graft materials were surgically implanted and inserted into the left thigh muscle. Mice were humanely killed at 1, 2, 3, 4, 6, 8, and 12 weeks. Then the muscle tissues in the vicinity of the implants were excised and processed for histology. Paraffin sections were stained with hematoxylin and eosin (H&E), the Von Kossa method, and Masson's trichrome. Some selected specimens were processed for transmission electron microscopic observation. After 1 week of implantation, the DynaGraft group showed calcium deposition on the collagen material and on the periphery of the DFDBA particles. Increased calcification and bone-forming cells were observed at 4-6 weeks. After 8 weeks, the implant formed a calcified nodule and only heavily mineralized connective tissue was observed at the implanted site. The group implanted with DFDBA powder showed calcification around the particulates. The collagen-sponge control group revealed no calcification or bone formation during the period of implantation. The light microscopic findings were confirmed by electron microscopy. Quantitative radiographic density DynaGraft and DFDBA graft followed sequentially over a period 120 days. It was concluded that a higher rate of calcification and bone formation was produced in the composite graft implant compared to the DFDBA implant. The composite graft material (DynaGraft), which contains both collagen and DFDBA, proved to be more effective for bone formation than particle components alone. PMID- 11787032 TI - The effect of structural characteristics on the in vitro bioactivity of hydroxyapatite. AB - In previous studies a film of hydroxylapatite (HA) was coated onto the inner pore surfaces of reticulated alumina for bone substitutes with the use of a so-called thermal deposition method. In this process, the HA films must be sintered at high temperatures for a strong adhesion to the alumina substrate. It has been found that high-temperature sintering inevitably changes the crystallinity of the coated HA, and in turn affects its bioactivity. Therefore, in this study, in vitro experiments were carried out to investigate the effects of structural changes on the in vitro bioactivity. The factors dominating in vitro bioactivity of HA, including surface area, degree of crystallinity, and temperature, were identified. The activation energy for volume diffusion was calculated for different in vitro solution temperatures. Also discussed is the underlying mechanism of growth and dissolution processes during the in vitro test. PMID- 11787033 TI - Prenatal diagnosis of trisomy 20 by chorionic villus sampling (CVS): a case report with long-term outcome. AB - A case of prenatally diagnosed non-mosaic trisomy 20 in cells cultured from a chorionic villus sample (CVS)is presented. The term placental karyotype was also non-mosaic trisomy 20. The karyotype of the newborn was 46,XY/47,XY,+20 in foreskin cultures and in a second skin culture; blood lymphocyte culture was 46,XY. Aside from diffuse, hypopigmentary swirls along the lines of Blaschko observed on his extremities and trunk, referred to as hypomelanosis of Ito, the patient is clinically normal at 8 3/4 years of age. In addition, he is one of the oldest reported cases of mosaic trisomy 20 confirmed after birth for which the clinical outcome has been monitored. This case demonstrates that these trisomy 20 findings are compatible with normal psychomotor development and phenotype. PMID- 11787034 TI - Dehydrated hereditary stomatocytosis: a cause of prenatal ascites. AB - Dehydrated hereditary stomatocytosis (DHS) is a rare congenital hemolytic anemia. We observed that some patients had presented with different prenatal or perinatal forms of edema in some kindreds. Within weeks or months after birth, these exhibited a spontaneous, complete and definitive resorption. We assumed that some DHS patients, who were born without edema before ultrasound was available, might nonetheless have exhibited this during the prenatal period. The present report follows up the first pregnancy in a woman with overt DHS, but not herself having a known history of perinatal effusions. Ultrasound revealed that the fetus displayed ascites that disappeared prior to birth. The neonate had DHS. Prenatal edema must therefore be more frequent in DHS than known until now. DHS is another cause of prenatal edema to be considered in the differential diagnosis. PMID- 11787035 TI - Split-hand/split-foot malformation with paternal mutation in the p63 gene. AB - We report the prenatal diagnosis at 16 weeks' gestation of bilateral split hand/split-foot malformation (SHSFM) with severe lobster claw deformity of hands and feet in a male fetus without associated malformations. A minor manifestation of SHSFM was present in the father with only mild bilateral foot involvement (syndactyly I-II; cleft II-III; left cutaneous syndactyly III-IV). Mutation analysis of the p63 gene on chromosome 3q27 showed a missense mutation 577A-->G (predicting amino acid substitution K193E) in the father. This mutation has not been reported so far in SHSFM but resembles the previously reported 580A-->G (predicting amino acid substitution K194E) in a family with SHSFM. PMID- 11787036 TI - Multicolour spectral karyotyping for complex chromosomal rearrangements in repeated abortion or congenital anomalies. AB - Advances in molecular cytogenetics, especially the technique of fluorescence in situ hybridization (FISH), have allowed more precise definition of chromosomal structures, which are difficult to identify using conventional G-banding. Recently, a novel approach based on hybridization of 24 fluorescent-labelled chromosome painting probes was developed, termed spectral karyotyping (SKY), which allows the simultaneous and differential colour display of all human chromosomes. We have used SKY to identify not only five parental complex translocation carriers but also minute chromosome rearrangements in the fetus. Here, we concentrate attention on the clinical application of SKY for prenatal diagnosis. PMID- 11787037 TI - Prenatal diagnosis of hydrocephalus-stenosis of the aqueduct of Sylvius by ultrasound in the first trimester of pregnancy. Report of two cases. AB - Hydrocephalus-stenosis of the acqueduct of Sylvius sequence (HSAS) is characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, agenesis of the corpus callosum and mental retardation. X-linked hydrocephalus is known to be due to mutations in the gene coding for the neural cell adhesion molecule L1 (L1-CAM) and diagnosis is made by identification of a mutation in the L1-CAM gene. Prenatal diagnosis of HSAS is usually suggested on ultrasound examination showing hydrocephalus in a male fetus associated with bilateral adducted thumbs. Mutation screening of the L1-CAM gene is indicated when neuropathological examination shows hypoplasia of the corticospinal tract associated with aqueductal stenosis. We report here two cases of HSAS diagnosed within the same family by ultrasound examination in the first trimester of pregnancy when bilateral adducted thumbs were the only early ultrasound marker. PMID- 11787038 TI - Prenatal interphase FISH diagnosis of PLP1 duplication associated with Pelizaeus Merzbacher disease. AB - A submicroscopic genomic duplication in Xq22.2 that contains the entire proteolipid protein 1 gene (PLP1) is responsible for the majority of Pelizaeus Merzbacher disease (PMD) patients. We previously developed an interphase FISH assay to screen for PLP1 duplications in PMD patients using peripheral blood and lymphoblastoid cell lines. This assay has been utilized as a clinical diagnostic test in our cytogenetics laboratory. To expand usage of the interphase FISH assay to prenatal diagnosis of PLP1 duplications, we examined three PMD families with PLP1 duplications utilizing aminiotic fluid samples. In two families the FISH assay revealed fetuses with PLP1 duplications, whereas the other fetus showed a normal copy number of PLP1. Haplotype analyses, as well as an additional FISH analysis using postnatal blood samples, confirmed the results of the prenatal analyses. Our study demonstrates utility of the interphase FISH assay in the prenatal diagnosis of PLP1 duplications in PMD. PMID- 11787039 TI - Association between congenital foot anomalies and gestational age at amniocentesis. AB - OBJECTIVES: Our objectives were to confirm the reported association between early amniocentesis and congenital foot anomalies as well as to report, for the first time, on the outcome of amniocenteses performed during the 13th and 14th weeks of gestation. METHODS: We conducted a triple cohort retrospective study of 4457 amniocenteses. Cohort definitions: early amniocentesis (EA), 11 weeks and 0/7 days to 12 weeks to 6/7 days; early midtrimester amniocentesis (EMA), 13 weeks and 0/7 days to 14 weeks and 6/7 days; and midtrimester amniocentesis (MA), 15 weeks and 0/7 days to 19 weeks and 6/7 days. Outcome measures were obtained by searching the Alberta Congenital Anomalies Surveillance System (ACASS) database for children born with foot anomalies represented by International Classification of Diseases version 9 (ICD-9) codes 754.5, 754.6 and 754.7. RESULTS: Incidences of congenital foot anomalies were: EA 11/980 (1.1%), EMA 11/2515 (0.4%), and MA 1/962 (0.1%). There is a significant difference between the EA and EMA cohorts (p=0.019) and between the EA and MA cohorts (p=0.003); however, these data suggest there is no difference between EMA and MA cohorts (p=0.11). CONCLUSIONS: Our incidence of congenital foot anomalies of 1.1% for women who underwent EA is similar to previously reported data, which further validates this association; however, our data also suggest that the foot anomaly risk may be limited to amniocenteses performed before the 13th week of gestation. PMID- 11787040 TI - Identification of triploid trophoblast cells in peripheral blood of a woman with a partial hydatidiform molar pregnancy. AB - In a woman with a partial hydatidiform molar pregnancy with 69,XXY karyotype, the presence of male fetal cells of trophoblastic origin was demonstrated in maternal blood by X/Y-chromosome specific PCR and by immunostaining combined with FISH on two cell populations isolated from maternal blood. Blood was obtained three weeks prior to the detection of fetal demise, at 13 weeks' gestation. Results were confirmed on formalin-fixed paraffin-embedded molar tissue, removed at 16 weeks' gestational age for therapeutic reasons. The results indicate that both plasma and cells from maternal peripheral blood might be useful for non-invasive prenatal diagnosis of fetal aneuploidies, as described in the current case with a partial molar pregnancy. PMID- 11787041 TI - Prenatal diagnosis of kyphomelic dysplasia. AB - Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by disproportionate dwarfism with shortening and bowing of the limbs, narrow chest, 11 ribs and metaphyseal flaring. Mental development is generally normal. We report the in utero ultrasound appearances and post-mortem radiographic findings of a 22-week-old male fetus suggestive of KD. A review of 19 previously reported patients with KD is also presented. PMID- 11787042 TI - The diagnostic performance of cytogenetic investigation in amniotic fluid cells and chorionic villi. AB - First-trimester chorionic villus sampling has not reached the popularity of second-trimester amniocentesis in prenatal cytogenetic diagnosis, in contrast to initial expectations. We investigated whether a difference in the diagnostic performances of cytogenetic investigation in amniotic fluid (AF) cells and chorionic villi in favour of AF-cells might justify this. Diagnostic performance was measured as laboratory failure rate, karyotype quality (G-band score, rate of follow-up samples, rate of wrong diagnoses), and karyotype representativity (rate of follow-up samples, rate of wrong diagnoses). From 1993-1999, 11 883 AF-samples were investigated (AF-cells). In chorionic villi, short term culture preparations solely were karyotyped from 1993-1996 (n=3499) (STC-villi), short and long-term culture preparations simultaneously provided a sufficient amount of tissue being available from 1997 onwards (n=1829) ((STC+LTC)-villi). Laboratory failure rates were the same after amniocentesis (0.40%) and chorionic villus sampling (0.50%). G-band scores (mean+/-SD) were equal in AF-cells (373+/-38.1) and LTC-villi (364+/-32.6) but significantly lower in STC-villi (311+/-34.6) (p=0.001). Follow up sampling rates because of quality reasons were the same in AF-cells (0.14%), STC- villi (0.13%) and (STC+LTC)-villi (0.11%). Two wrong diagnoses turned up among AF-cells. Follow-up sampling rates because of representativity reasons differed significantly between AF-cells (0.10%), (STC+LTC)-villi (1.31%), and STC villi (1.99%) (p<0.001). However, the ratios of the total numbers of follow-up samples and uncertain or abnormal cytogenetic results in STC, and (STC+LTC)-villi at cytogenetic risks > or =3% (0.132 and 0.160, respectively) were equal to that in AF-cells at risks <3% (0.155). Two wrong diagnoses were made in STC-villi. Diagnostic performance improved in the rank order of STC-villi, (STC+LTC)-villi and AF-cells. At cytogenetic risks > or =3%, (STC+LTC)-villi showed a diagnostic performance equal to that in AF-cells. This might justify a selective use of chorionic villus sampling. PMID- 11787043 TI - Split notochord syndrome - prenatal ultrasonographic diagnosis. AB - Split notochord syndrome is a rare condition that is characterized by a persistent connection of the gut and dorsal skin of the back, an enteric cyst and vertebral anomalies. We present two cases in which prenatal ultrasound showed polyhydramnios. In one case it was associated with vertebral abnormalities and a right-sided mediastinal cyst found to be the stomach. Postnatal evaluation confirmed the diagnosis of split notochord syndrome. The association of sonographic findings of hydramnios, thoracic cysts and vertebral anomalies suggests prenatal diagnosis of split notochord syndrome. PMID- 11787044 TI - Minor sonographic signs of trisomy 21 at 15-20 weeks' gestation in fetuses born without malformations: a prospective study. AB - A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (> or =35) or triple-test results (risk> or =1/380). The study covered a 36-month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15-19 week' gestation. Only fetuses with normal karyotype or trisomy 21 were considered. Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%). PMID- 11787045 TI - Prenatal diagnosis of glutaric acidemias. PMID- 11787046 TI - Duplication of chromosome 2 in association with ventriculomegaly - a case report. AB - This is a case report of the prenatal diagnosis of a de novo interstitial duplication of chromosome 2 (46,XX,dup(2)(p13p21) de novo) with an associated phenotypic abnormality. This chromosomal duplication is rare, only one has previously been described prenatally. Postnatal reports of similar duplications in this region have described associated dysmorphic features and significant neurodevelopmental delay. In our case, the only ultrasound finding was moderately severe ventriculomegaly. At post-mortem, ventriculomegaly was confirmed and there was associated macrocephaly (head circumference above the 97th centile) with no dysmorphic features seen. PMID- 11787047 TI - Improvement of mesenteric superior artery Doppler velocimetry by amnio-infusion in fetal gastroschisis. AB - This study aimed to analyse the influence of amnio-infusion on superior mesenteric Doppler velocimetry and to correlate Doppler data with outcome in fetuses presenting with gastroschisis. Umbilical and intra- and extra-abdominal superior mesenteric artery Doppler velocimetry was measured prospectively before and after amnio-infusion in fetuses with gastroschisis. Doppler index values and changes were correlated with the following outcome parameters: importance of fibrous coating, duration of hospitalization in the neonatal intensive care unit, total duration of hospitalization, duration of parenteral feeding, duration of ventilatory assistance, and the interval to initiation of oral feeding. A significant improvement of diastolic flow was observed in the extra-abdominal superior mesenteric artery with amnio-infusion. No similar change was seen in the intra-abdominal superior mesenteric or in the umbilical artery. Pre-amnioinfusion extra-abdominal mesenteric Doppler index was correlated with maximal diameter of exteriorized bowel and slightly with duration of hospitalization in the neonatal intensive care unit, but no other relation between Doppler index and outcome parameter could be ascertained. Amnio-infusion induces modifications in the vascularization of exteriorized bowel in gastroschisis. This could partly explain the beneficial effect of this procedure on fetal gut. PMID- 11787048 TI - Sequential first and second trimester screening tests: correlation of the markers' levels in normal versus Down syndrome affected pregnancies. PMID- 11787049 TI - Maternal serum screening marker levels in consanguineous couples. PMID- 11787050 TI - IGF-1 induces Pin1 expression in promoting cell cycle S-phase entry. AB - Insulin-like growth factor I (IGF-1) is a well-established mitogen to many different cell types and is implicated in progression of a number of human cancers, notably breast cancer. The prolyl isomerase Pin1 plays an important role in cell cycle regulation through its specific interaction with proteins that are phosphorylated at Ser/Thr-Pro motifs. Pin1 knockout mice appear to have relatively normal development yet the Pin1(-/-)mouse embryo fibroblast (MEF) cells are defective in re-entering cell cycle in response to serum stimulation after G0 arrest. Here, we report that Pin1(-/-) MEF cells display a delayed cell cycle S-phase entry in response to IGF stimulation and that IGF-1 induces Pin1 protein expression which correlates with the induction of cyclin D1 and RB phosphorylation in human breast cancer cells. The induction of Pin1 by IGF-1 is mediated via the phosphatidylinositol 3-kinase as well as the MAP kinase pathways. Treatment of PI3K inhibitor LY294002 and the MAP kinase inhibitor PD098059, but not p38 inhibitor SB203580, effectively blocks IGF-1-induced upregulation of Pin1, cyclin D1 and RB phosphorylation. Furthermore, we found that Cyclin D1 expression and RB phosphorylation are dramatically decreased in Pin1(-/-) MEF cells. Reintroducing a recombinant adenovirus encoding Pin1 into Pin1(-/-) MEF cells restores the expression of cyclin D1 and RB phosphorylation. Thus, these data suggest that the mitogenic function of IGF-1 is at least partially linked to the induction of Pin1, which in turn stimulates cyclin D1 expression and RB phosphorylation, therefore contributing to G0/G1-S transition. PMID- 11787051 TI - Nuclear estrogen receptor II (nER-II) is involved in the estrogen-dependent ribonucleoprotein transport in the goat uterus I. Localization of nER-II in snRNP. AB - Exposure of goat uterine nuclei to estradiol in vitro results in an immediate exit of ribonucleoproteins (RNP) from the nuclei to the medium. This RNP exit appears to be mediated by an estrogen receptor localized in small nuclear ribonucleoproteins containing U1 and U2 snRNA. Available evidence indicates that the estrogen receptor involved is not the ERalpha, but an alternative form, which is also a 66 kDa protein. This is the nuclear estrogen receptor II (nER-II) that has no DNA-binding capacity. The transport is estrogen-specific since non estrogenic steroids do not stimulate the transport of the RNP where the receptor is localized. PMID- 11787052 TI - Nuclear estrogen receptor II (nER-II) is involved in the estrogen-dependent ribonucleoprotein transport in the goat uterus: II. Isolation and characterization of three small nuclear ribonucleoprotein proteins which bind to nER-II. AB - Three proteins of a goat uterine small nuclear ribonucleoprotein (snRNP) fraction, which bind to nuclear estrogen receptor-II (nER-II) have been isolated and purified. These are the p32, p55, and p60 of which p32 is the major nER-II binding protein. Indirect evidence reveals that p32 binds to the nuclear export signal (NES) on the nER-II. nER-II is a snRNA binding protein while p32 does not bind to the RNA. nER-II along with p32 and p55 form an effective Mg(++)ATPase complex, the activation of which appears to be the immediate reason behind the RNP exit from the nuclei following estradiol exposure. The three nER-II binding proteins bind to the nuclear pore complex; nER-II does not possess this property. PMID- 11787054 TI - Ethanolamine is a co-mitogenic factor for proliferation of primary hepatocytes. AB - Mature adult parenchymal hepatocytes can enter the S phase in the presence of growth factors such as HGF and EGF, but rarely proliferate in culture. We hypothesized that the cell cycle of hepatocytes in culture is restricted before G(2)/M phase and we attempted to identify the factor that induces cell cycle progression. We found that the conditioned medium from long-term cultured hepatocytes contained co-mitogenic activity with other growth factors, which was attributed to ethanolamine (Etn). Etn induced not only DNA synthesis but also cell replication of cultured hepatocytes with various other growth factors. Etn and HGF synergistically induced cyclin D(1), A and B expression, however, only cyclin B but not cyclin A formed a complex with Cdc2. In addition, Etn combined with HGF enhanced PKCbetaII expression and translocated PKCbetaII to the plasma membrane, and induced filopodia formation, which was inhibited by an antisense oligonucleotide against PKCbetaII. In addition, blocking the cytoskeleton rearrangement with inhibitors (colchicine, cytochalasin D, or chlerythrine (a specific PKC inhibitor)) inhibited cyclin expression and cell proliferation. Although Etn enhanced the downstream product, cellular phosphatidylethanolamine (PE), PE itself did not show any Etn-like activities on hepatocytes. Taken together, our results indicate that Etn functions as a co-replication factor to promote the cell cycle of mature hepatocytes to G(2)/M phase in the presence of growth factors. The activity is thought to be mediated by PKCbetaII-dependent cyclin B expression. PMID- 11787053 TI - Cell density dependent regulation of AP-1 activity is important for chondrogenic differentiation of C3H10T1/2 mesenchymal cells. AB - The multipotential C3H10T1/2 mesenchymal cells undergo chondrogenic differentiation only when seeded as high-density micromass cultures, particularly upon treatment with bone morphogenetic protein-2 (BMP-2). The molecular mechanism(s) responsible for the cell density-dependent onset of cartilage specific gene expression is presently unknown. Interestingly, a number of recent studies have indicated that activating protein-1 (AP-1), a well known downstream target of the mitogenic activated protein kinase (MAP kinase) signaling pathway, is a target of chondrogenic/osteogenic growth factors such as BMP-2, and plays a role in osteogenic gene regulation as well as in chondrogenic differentiation. The aim of this study is to examine the density-dependent alteration in the level and binding activity of AP-1 and its functional involvement in C3H10T1/2 mesenchymal chondrogenesis. To measure the activity of the AP-1 transcription factor, we generated a pool of stable C3H10T1/2 cell lines harboring a luciferase expression vector driven by a concatamer of an efficient AP-1 response element (AP1-10T1/2 cells). Luciferase activity of AP1-10T1/2 cultures was found to decrease sharply with increase in cell density, either as a function of culture time or initial cell seeding densities. In C3H10T1/2 micromass cultures undergoing chondrogenesis, AP-1 activity was further reduced and then maintained at a low, steady level for the entire 3-4 day culture period. AP-1 activity in micromass cultures was not significantly affected by BMP-2 treatment, but chondrogenesis was compromised upon competitive inhibition of AP-1 activity with a double-stranded AP-1 binding oligonucleotide. The level of AP-1 binding correlated with the activity of its response element but not with the levels of its leucine-zipper containing subunits, c-Jun and c-Fos. These findings suggest that a cell density-dependent, low but steady level of AP-1 binding and activity is required for promoting the chondrogenic potential of C3H10T1/2 cells. PMID- 11787055 TI - Mechanical regulation of IGF-I and IGF-binding protein gene transcription in bladder smooth muscle cells. AB - Mechanical forces are well known to modulate smooth muscle cell growth and synthetic phenotype. The signals controlling this process are complex and potentially involve changes in the expression of peptide growth factor genes such as those of the insulin-like growth factor (IGF) system. This study was designed to investigate the mechanical regulation of IGF-I and the binding proteins for IGF (IGFBPs) in smooth muscle cells cultured on a deformable surface and subjected to cyclic stretch. Using the RNase protection assay, we found that the application of a cyclic biaxial strain to cells induced a 2.5- to 4-fold increase in IGF-I mRNA levels after 8 h and an even greater increase after 16-24 h of stretch. This change was not affected by variations in the magnitude of the applied strain but was attenuated ( approximately 40%) when cells were treated with antagonists for angiotensin II receptors. Furthermore, the transcript levels of the three major IGF binding proteins produced in smooth muscle cells, e.g., IGFBP-2, IGFBP-4, and IGFBP-5, varied between stretched and control cells. Both IGFBP-2 and IGFBP-4 mRNA levels were consistently reduced in stretched cells but remained comparable to those of the control cells when the angiotensin II transducing pathway was blocked by inhibitors prior to the application of mechanical strain. Conversely, the gene expression of IGFBP-5 was upregulated in stretched cells, and neutralizing antibodies to IGF-I blocked this activation. Similarly, pharmacologic inhibition of the phosphatidylinositol 3-kinase, an important component of the IGF receptor transduction pathway, inhibited IGFBP-5 gene expression in stretched cells. These results suggest that the downstream effects of mechanical strain on IGF-I and IGFBP transcript levels are mediated, to greater or lesser extent, either through an angiotensin II tranducing pathway or via a feedback loop involving the autocrine secretion of IGF-I itself. PMID- 11787056 TI - Heat shock proteins of adult and embryonic human ocular lenses. AB - We investigated the presence and distribution of heat shock proteins, HSP-70 [Horwitz, J. 1992. Proc Natl Acad Sci 89:10449-10453], HSP-40, HSc-70, HSP-27, and alphabeta-crystallin in different regions of adult and fetal human lenses and in aging human lens epithelial cells. This study was undertaken because heat shock proteins may play an important role in the maintenance of the supramolecular organization of the lens proteins. Human adult and fetal lenses were dissected to separate the epithelium, superficial cortex, intermediate cortex, and nucleus. The water soluble and insoluble protein fractions were separated by SDS-PAGE, and transferred to nitrocellulose paper. Specific antibodies were used to identify the presence of heat shock proteins in distinct regions of the lens. HSP-70 [Horwitz, 1992], HSP-40, and HSc-70 immunoreactivity was mainly detected in the epithelium and superficial cortical fiber cells of the adult human lens. The small heat shock proteins, HSP-27 and alphabeta-crystallin were found in all regions of the lens. Fetal human lenses showed immunoreactivity to all heat shock proteins. An aging study revealed a decrease in heat shock protein levels, except for HSP-27. The presence of HSP-70 [Horwitz, 1992], HSP 40, and HSc-70 in the epithelium and superficial cortical fiber cells imply a regional cell specific function, whereas the decrease of heat shock protein with age could be responsible for the loss of optimal protein organization, and the eventual appearance of age-related cataract. PMID- 11787057 TI - Estrogen-induced osteogenesis in mice is associated with the appearance of Cbfa1 expressing bone marrow cells. AB - Cbfa1 is a transcription factor recognised as being involved in early osteoblast differentiation during embryonic skeletogenesis. To determine whether Cbfa1 plays a similar role in bone formation in the adult, we analysed whether its expression is altered during estrogen-induced osteogenesis, following our recent studies which suggest that this response involves the generation of early osteoblast precursors within bone marrow. To facilitate identification of Cbfa1-expressing cells, these studies were performed in mice heterozygous for a cbfa1 gene deletion (cbfa1(+/-)) using beta-galactosidase (lacZ) as a genetic marker. Cbfa1 expressing cells were identified by lacZ staining of longitudinal sections of the proximal tibial metaphysis. Treatment of cbfa1(+/-) mice with 17beta-estradiol 0.5 mg/week for 24 days led to the appearance of new cancellous bone surfaces. This response was associated with a marked increase in number of Cbfa1-expressing cells within the metaphysis, consisting not only of osteoblasts on bone surfaces but also of cells within the adjacent bone marrow. We subsequently enumerated Cbfa1-expressing cells at earlier time-points following estrogen, in sections co stained for ALP activity. After 4 days of estrogen treatment, a population of cells appeared within the marrow cavity which expressed Cbfa1, but were negative for ALP. At later time-points, large numbers of Cbfa1 + bone marrow cells were still present, but the majority of these were close to new trabecular bone surfaces at sites which showed high levels of ALP activity. An equivalent distribution of Cbfa1-expressing cells was observed in further studies where Cbfa1 expression was analysed in wild-type mice by immunohistochemistry. We conclude that estrogen-induced osteogenesis is associated with the appearance of a population of Cbfa1-expressing cells within bone marrow, which we hypothesize to represent the osteoblast precursor population responsible for subsequent new bone formation. PMID- 11787058 TI - ATP stimulates human placental 11beta-hydroxysteroid dehydrogenase type 2 activity by a novel mechanism independent of phosphorylation. AB - The human placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is believed to play a key role in fetal development since this enzyme protects the fetus from exposure to high levels of maternal cortisol by virtue of converting maternal cortisol to its inert metabolite cortisone. The present study was undertaken to examine the effect of ATP on 11beta-HSD2 activity in human placental microsomes. Enzyme activity, reflected by the rate of conversion of cortisol to cortisone, was stimulated more than six-fold by 0.5 mM ATP (EC(50) = 0.2 mM). Such stimulation appears to be mediated through a novel mechanism independent of ATP-induced phosphorylation of the reaction components since AMP PNP, a non-hydrolyzable analogue of ATP, was equally effective. The ATP-induced stimulation of 11beta-HSD2 activity is adenine nucleotide specific in that a similar stimulation was observed with ADP and AMP but not with CTP, GTP, or UTP. Furthermore, ATP increased the maximal velocity (V(max)) of the 11beta-HSD2 catalyzed conversion of cortisol to cortisone without altering the apparent K(m) of 11beta-HSD2 for cortisol, suggesting that ATP may stimulate enzyme activity by interacting with the enzyme at a site other than that involved in substrate binding. In conclusion, the present study has identified ATP as a novel regulator of human placental 11beta-HSD2 in vitro. It is conceivable that intracellular ATP may have a profound effect on 11beta-HSD2 function in vivo. PMID- 11787059 TI - Proline-rich transcript of the brain (prtb) is a serum-responsive gene in osteoblasts and upregulated during adhesion. AB - To characterize the temporal expression of genes that play a functional role during the process of osteoblast adhesion, we used differential display (DD-PCR) on mRNA isolated from attached vs. suspended osteoblasts. A 200-bp fragment displaying upregulated expression after 30 and 60 min adhesion was isolated, sequenced, and showed 97% homology to prtb, previously showed to be expressed in mouse brain. Northern analysis confirmed a two-fold increase in prtb message during adhesion to tissue culture polystyrene, both in the presence or absence of surface-adsorbed serum proteins. Serum stimulation alone was also able to induce prtb expression, although to a lesser extent, in suspension cells. Strong prtb expression was also detected in both brain and bone of adult rats. Furthermore, prtb expression analysis during MC3T3-E1 cell differentiation revealed high expression levels independent of proliferation (day 0-7), matrix maturation (day 7-14), and mineralization (day 14-31). Time course analysis of prtb expression during adhesion of sensitized osteoblasts to serum-protein coated surfaces showed robust mRNA expression at 5 min post-plating and a peak at 10 min. The two known serum-inducible immediate early genes c-fos and c-jun showed similar expression kinetics, with c-jun mRNA levels peaking at 15 min and c-fos at 20 min. Based on these data, we hypothesize that prtb may function as an immediate early, serum responsive, and adhesion-inducible gene with possible involvement in processes such as cell cycle control, adhesion, and proliferation. PMID- 11787060 TI - Macrophages take up triacylglycerol-rich emulsions at a faster rate upon co incubation with native and modified LDL: An investigation on the role of natural chylomicrons in atherosclerosis. AB - Chylomicrons play a role in atherosclerosis, however, because the mechanisms involved in the cell uptake of these particles are not fully understood, investigations were carried out using a radioactively labeled protein-free triacylglycerol-rich emulsion incubated with peritoneal macrophages obtained from normal and apoE-knockout mice. Experiments were done in the presence of substances that inhibit several endocytic processes: EDTA for low density lipoprotein receptor, fucoidan for scavenger receptor, cytochalasin B for phagocytosis, and a lipopolysaccharide for lipoprotein lipase. In addition, triacylglycerol-rich emulsions were also prepared in the presence of native or modified radioactively labeled low density lipoprotein particles that are known to accumulate in the arterial intima. Probucol was also used to prevent the possible role played by an antioxidant in triacylglycerol-rich emulsion uptake. We have shown that triacylglycerol-rich emulsion alone is taken up by a coated pit-dependent mechanism, mediated by macrophage secretion of apolipoprotein E. Furthermore, native, aggregated, acetylated, and moderately macrophage-oxidized low density lipoprotein stimulate the uptake of a triacylglycerol-rich emulsion through several mechanisms such as an actin-dependent pathway, scavenger receptors, and lipolysis mediated by lipoprotein lipase. On the other hand, in spite of the interaction of low density lipoprotein forms with a triacylglycerol rich emulsion, the cellular triacylglycerol-rich emulsion uptake is impaired by copper-oxidized low density lipoprotein, possibly due to its diminished affinity towards lipoprotein lipase. We have also shown that macrophages take up aggregated low density lipoprotein better than the acetylated or oxidized forms of low density lipoprotein. PMID- 11787061 TI - Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts. AB - Genomic methylation, which influences many cellular processes such as gene expression and chromatin organization, generally declines with cellular senescence although some genes undergo paradoxical hypermethylation during cellular aging and immortalization. To explore potential mechanisms for this process, we analyzed the methylating activity of three DNA methyltransferases (Dnmts) in aging and immortalized WI-38 fibroblasts. Overall maintenance methylating activity by the Dnmts greatly decreased during cellular senescence. In immortalized WI-38 cells, maintenance methylating activity was similar to that of normal young cells. Combined de novo methylation activity of the Dnmts initially decreased but later increased as WI-38 cells aged and was strikingly elevated in immortalized cells. To further elucidate the mechanisms for changes in DNA methylation in aging and immortalized cells, the individual Dnmts were separated and individually assessed for maintenance and de novo methylating activity. We resolved three Dnmt fractions, one of which was the major maintenance methyltransferase, Dnmt1, which declined steadily in activity with cellular senescence and immortalization. However, a more basic Dnmt, which has significant de novo methylating activity, increased markedly in activity in aging and immortalized cells. We have identified this methyltransferase as Dnmt3b which has an important role in neoplastic transformation but its role in cellular senescence and immortalization has not previously been reported. An acidic Dnmt we isolated also had increased de novo methylating activity in senescent and immortalized WI-38 cells. These studies indicate that reduced genome-wide methylation in aging cells may be attributed to attenuated Dnmt1 activity but that regional or gene-localized hypermethylation in aging and immortalized cells may be linked to increased de novo methylation by Dnmts other than the maintenance methyltransferase. PMID- 11787062 TI - beta- and gamma-actin genes differ in their mechanisms of down-regulation during myogenesis. AB - During the differentiation of myoblasts to form myotubes, the expression patterns of the different actin isoforms change. The cytoplasmic actins, beta and gamma, are down-regulated and the muscle specific isoforms are up-regulated. The region responsible for the down-regulation of the beta-actin gene has been located in the 3'end of the gene. Since the beta- and gamma-actin genes arose from a gene duplication (Erba et al. [1988] J. Cell. Biol. 8:1775-1789), it is possible that the region responsible for down-regulation of the gamma-actin gene may also be in the 3'end of the gene. We have tested this by transfection of human gamma-actin gene constructs into myogenic C2 cells. To our surprise, we found that the region responsible for down-regulation of the gamma-actin gene during differentiation is not in the 3' end of the gene in contrast to that for beta-actin. Rather, we found that intron III is required for appropriate down-regulation of gamma-actin during myogenesis. Intron III containing transcripts from the gamma-actin gene were also found to accumulate during myogenesis. We, therefore, propose that excision of intron III from the primary transcript is inhibited during myogenesis resulting in degradation of the RNA. Removal of intron III from the gene allows it to escape this regulatory mechanism. PMID- 11787063 TI - Support vector machines for prediction of protein subcellular location by incorporating quasi-sequence-order effect. AB - Support Vector Machine (SVM), which is one class of learning machines, was applied to predict the subcellular location of proteins by incorporating the quasi-sequence-order effect (Chou [2000] Biochem. Biophys. Res. Commun. 278:477 483). In this study, the proteins are classified into the following 12 groups: (1) chloroplast, (2) cytoplasm, (3) cytoskeleton, (4) endoplasmic reticulum, (5) extracellular, (6) Golgi apparatus, (7) lysosome, (8) mitochondria, (9) nucleus, (10) peroxisome, (11) plasma membrane, and (12) vacuole, which account for most organelles and subcellular compartments in an animal or plant cell. Examinations for self-consistency and jackknife testing of the SVMs method were conducted for three sets consisting of 1,911, 2,044, and 2,191 proteins. The correct rates for self-consistency and the jackknife test values achieved with these protein sets were 94 and 83% for 1,911 proteins, 92 and 78% for 2,044 proteins, and 89 and 75% for 2,191 proteins, respectively. Furthermore, tests for correct prediction rates were undertaken with three independent testing datasets containing 2,148 proteins, 2,417 proteins, and 2,494 proteins producing values of 84, 77, and 74%, respectively. PMID- 11787064 TI - Growth factor-mediated altered expression and regulation of S-adenosylmethionine decarboxylase in a H-ras transformed cell line capable of malignant progression. AB - Mammalian S-adenosylmethionine decarboxylase (SAMDC) is a regulatory activity, which is involved in the biosynthesis of polyamines. The polyamines, namely putrescine, spermidine, and spermine, are essential for mammalian cell proliferation. SAMDC expression was examined in a H-ras transformed cell capable of metastasis formation. Serum stimulation of these cells resulted in increased SAMDC mRNA and enzyme activity expression. The effect of several physiologically relevant growth factors on SAMDC expression was also determined. SAMDC mRNA expression was increased in response to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) stimulation but was unaffected by transforming growth factor beta(1) (TGF-beta(1)) and platelet derived growth factor (PDGF). Increased SAMDC enzyme activity occurred in response to exposure to EGF, bFGF, TGF-beta(1), and PDGF. The EGF and bFGF mediated alterations in SAMDC mRNA expression were apparently not due to alterations in the transcriptional apparatus but occurred partly through post-transcriptional mechanisms involving increased SAMDC message stability. EGF and bFGF were able both to cooperate with cycloheximide, an inhibitor of protein synthesis, to augment the expression of SAMDC mRNA. Furthermore, studies with NIH-3T3 fibroblasts transfected with either the normal basic fibroblast growth factor coding sequence that lacks a known secretory signal sequence or a chimeric bFGF sequence that targets the growth factor to the secretory pathway revealed that increased SAMDC expression occurred only in those cells which contained the chimeric bFGF sequence that targets the growth factor to the secretory pathway suggesting that the increase in expression of SAMDC occurs through an autocrine mechanism. Increased ornithine decarboxylase (ODC) expression was found to occur in both types of bFGF transfected cells suggesting that altered ODC expression in response to bFGF stimulation may occur through both autocrine and intracrine mechanisms. In addition, a correlation was found to exist between SAMDC expression and regulation in response to growth factor stimulation and malignant potential. This correlation supports the view that growth factor induced alterations in SAMDC expression, although not sufficient on their own to induce metastasis, are important in the promotion and establishment of events important to the phenotype expressed by H-ras transformed cells capable of malignant progression. PMID- 11787065 TI - Effect of fibroblast growth factors 1, 2, 4, 5, 6, 7, 8, 9, and 10 on avian chondrocyte proliferation. AB - It has been demonstrated that fibroblast growth factor receptors are key regulators of endochondral bone growth. However, it has not been determined what fibroblast growth factor ligand(s) (FGFs) are important in this process. This study sought to determine whether FGFs 1, 2, 4, 5, 6, 7, 8, 9, and 10 were capable of stimulating avian chondrocyte proliferation in vitro. We have found that FGFs 2, 4, and 9 strongly stimulate avian chondrocyte proliferation while FGFs 6 and 8 stimulate proliferation to a lesser extent. RT-PCR indicates that FGF-2 and FGF-4 are expressed in the postnatal avian epiphyseal growth plate (EGP) while FGF-8 and FGF-9 are not. Thus, FGF-2 and FGF-4 stimulate chondrocyte proliferation and are both present in the EGP. This suggests that FGF-2 and FGF-4 may be important ligands, in vivo, for the regulation of endochondral bone growth. These observations coupled with our observation that multiple avian FGF receptors (Cek1, Cek2, Cek3, and FREK) are expressed in proliferative chondrocytes highlights the complexity of FGF signaling pathways in postnatal endochondral bone growth. PMID- 11787066 TI - Neuroprotective MK801 is associated with nitric oxide synthase during hypoxia/reoxygenation in rat cortical cell cultures. AB - The neuroprotective effect of MK801 against hypoxia and/or reoxygenation-induced neuronal cell injury and its relationship to neuronal nitric oxide synthetase (nNOS) expression were examined in cultured rat cortical cells. Treatment of cortical neuronal cells with hypoxia (95% N(2)/5% CO(2)) for 2 h followed by reoxygenation for 24 h induced a release of lactate dehydrogenase (LDH) into the medium, and reduced the protein level of MAP-2 as well. MK801 attenuated the release of LDH and the reduction of the MAP-2 protein by hypoxia, suggesting a neuroprotective role of MK801. MK801 also diminished the number of nuclear condensation by hypoxia/reoxygenation. The NOS inhibitors 7-nitroindazole (7-NI) and N (G)-nitro-L-arginine methyl ester (L-NAME), as well as the Ca(2+) channel blocker nimodipine, reduced hypoxia-induced LDH, suggesting that nitric oxide (NO) and calcium homeostasis contribute to hypoxia and/or the reoxygenation induced cell injury. The levels of nNOS immunoactivities and mRNA by RT-PCR were enhanced by hypoxia with time and, down regulated following 24 h reoxygenation after hypoxia, and were attenuated by MK801. In addition, the reduction of nNOS mRNA levels by hypoxia/reoxygenation was also diminished by MK801. Further delineation of the mechanisms of NO production and nNOS regulation are needed and may lead to additional strategies to protect neuronal cells against hypoxic/reoxygenation insults. PMID- 11787067 TI - FAK regulates tyrosine phosphorylation of CAS, paxillin, and PYK2 in cells expressing v-Src, but is not a critical determinant of v-Src transformation. AB - FAK (focal adhesion kinase) is a nonreceptor protein-tyrosine kinase activated by tyrosine phosphorylation following integrin-mediated cell adhesion. Oncogenic Src promotes enhanced and deregulated FAK tyrosine phosphorylation which has been proposed to contribute to altered cell growth and/or morphological properties associated with transformation. In this study, an inducible FAK expression system was used to study the potential role of FAK in v-Src transformation. Our results portray FAK as a major v-Src substrate that also plays a role in recruiting v-Src to phosphorylate substrates CAS (Crk-associated substrate) and paxillin. The FAK Tyr-397 autophosphorylation site was necessary for this scaffolding function, but was not required for v-Src to stably interact with and phosphorylate FAK. FAK was also shown to negatively regulate v-Src mediated phosphorylation of the FAK related kinase PYK2. Despite these effects, FAK does not play an essential role in targeting v-Src to major cellular substrates including CAS and paxillin. Nor is FAK strictly required to achieve the altered morphological and growth characteristics of v-Src transformed cells. PMID- 11787068 TI - Modulation of insulin transport in rat brain microvessel endothelial cells by an ecto-phosphatase activity. AB - The physiological function of alkaline phosphatase (ALP) remains controversial. It was recently suggested that this membrane-bound enzyme has a role in the modulation of transmembranar transport systems into hepatocytes and Caco-2 cells. ALP activity expressed on the apical surface of blood-brain barrier cells, and its relationship with (125)I-insulin internalization were investigated under physiological conditions using p-nitrophenylphosphate (p-NPP) as substrate. For this, an immortalized cell line of rat capillary cerebral endothelial cells (RBE4 cells) was used. ALP activity and (125)I-insulin internalization were evaluated in these cells. The results showed that RBE4 cells expressed ALP, characterized by an ecto-oriented active site which was functional at physiological pH. Orthovanadate (100 microM), an inhibitor of phosphatase activities, decreased both RBE4-ALP activity and (125)I-insulin internalization. In the presence of L arginine (1 mM) or adenosine (100 microM) RBE4-ALP activity and (125)I-insulin, internalization were significantly reduced. However, D-arginine (1 mM) had no significant effect. Additionally, RBE4-ALP activity and (125)I-insulin internalization significantly increased in the presence of the bioflavonoid kaempferol (100 microM), of the phorbol ester PMA (80 nM), IBMX (1 mM), progesterone (200 microM and 100 microM), beta-estradiol (100 microM), iron (100 microM) or in the presence of all-trans retinoic acid (RA) (10 microM). The ALP inhibitor levamisole (500 microM) was able to reduce (125)I-insulin internalization to 69.1 +/- 7.1% of control. Our data showed a positive correlation between ecto-ALP activity and (125)I-insulin incorporation (r = 0.82; P < 0.0001) in cultured rat brain endothelial cells, suggesting that insulin entry into the blood-brain barrier may be modulated through ALP. PMID- 11787069 TI - Genomic cloning and promoter analysis of the GAHSP40 gene. AB - The new heat shock protein (GAHSP40), which binds to Gadd34, is a member of the Hsp40 family gene and has a J domain, which is similar to bacterial DNAJ. We have isolated and sequenced the mouse GAHSP40 gene including 1.6 kb of the 5'-flanking region. Primer extension analysis revealed that the transcription initiation site was located 36-bp upstream of the ATG translation initiation codon. In order to identify the heat-responsive regions in the GAHSP40, NIH3T3 cells were transiently transfected with a series of 5' terminus-truncated mutants of the GAHSP40 promoter linked to the luciferase reporter gene. We found that the region of -284 to -184 bp from initiation start site responded to heat shock treatment. By the gel shift analysis, we found the heat shock elements (HSEs) located in this region from -257 to -225. This HSEs has five 5 bp motifs. The transfection studies using HSEs mutant vectors revealed that those 3' two 5 bp motifs are essential for heat responsive transcription. PMID- 11787070 TI - The cellular prion protein: a new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells. AB - Prion diseases are characterized by the presence of an abnormal isoform of the cellular prion protein (PrPc) whose physiological role still remains elusive. To better understand the function of PrPc, it is important to identify the different subcellular localization(s) of the protein and the different partners with which it might be associated. In this context, the PrPc-lectins interactions are investigated because PrPc is a sialoglycoprotein which can react with lectins which are carbohydrate-binding proteins. We have previously characterized a nuclear lectin CBP70 able to recognize N-acetyl-beta-D-glucosamine residues in HL60 cells. Using confocal immunofluorescence, flow-cytofluorometry, and Western blotting, we have found that PrPc is expressed in the nucleus of the NB4 human promyelocytic leukemia cell line. It was also found that the lectin CBP70 is localized in NB4 cell nuclei. Moreover, several approaches revealed that PrPc and CBP70 are colocalized in the nucleus. Immunoprecipitation experiments showed that these proteins are coprecipitated and interact via a sugar-dependent binding moiety. In conclusion, PrPc and CBP70 are colocalized in the nuclear compartment of NB4 cells and this interaction may be important to better understand the biological function and possibly the conversion process of PrPc into its pathological form (PrPsc). PMID- 11787071 TI - Mapping of functional epitopes of osteopontin by monoclonal antibodies raised against defined internal sequences. AB - Osteopontin (OPN) is a secreted protein that has been implicated in diverse physiological and pathological processes. OPN can bind to integrins, via GRGDS or SVVYGLR amino acid sequences, and to other cell surface receptors, and many of OPN's functions are likely mediated via cell adhesion and subsequent signaling. Here we developed and characterized a series of five monoclonal antibodies, raised to distinct internal peptide sequences of human OPN, and have used these sequence-specific reagents, along with the previously described anti-OPN monoclonal antibody mAb53, to map functional epitopes of OPN that are important to cell adhesion and migration. All antibodies were reactive with native as well as recombinant human OPN. One antibody (2K1) raised against the peptide VDTYDGRGDSVVYGLRS could inhibit RGD-dependent cell binding to OPN, with an efficacy comparable to that of mAb53. Furthermore, 2K1 could inhibit alpha9 integrin-dependent cell binding to OPN. The epitope recognized by 2K1 was not destroyed by thrombin digestion, whereas mAb53 has been shown to be unable to react with OPN following thrombin cleavage. The two distinct epitopes defined by 2K1 and mAb53 antibodies are closely related to the SVVYGLR cell-binding domain and the GLRSKS containing thrombin cleavage site, respectively, and are involved in cell binding and cell migration. PMID- 11787072 TI - 'Fairness and reasonableness of the child's decision:' a proposed legal standard for children's participation in medical decision making. AB - Using as illustration the case of Nikolas E., a six-year-old child with HIV/AIDS, this article considers the competing rights of children, parents, and state in cases involving pediatric medical disputes. The article outlines arguments in favor of and against children's participation in medical decisions and describes legal standards currently used in resolving pediatric medical disputes. The article then proposes adoption of a new legal standard described as the 'fairness and reasonableness of the child's decision,' and articulates advantages and disadvantages of such an approach, as well as the factors that should be considered in implementing the standard. Finally, the article argues for a methodology for including children's wishes in pediatric medical decision making that is based upon Monahan and Walker's model for including social science evidence in legal contexts and evaluates alternative strategies for including children meaningfully in the process of making medical decisions that affect them. PMID- 11787074 TI - Black and white differences in the perception of justice. AB - This study examined how African Americans and Whites view the justice system in the United States. Three hundred and eighteen research participants were recruited from the campus of a local community college. The research participants viewed one of four different videotaped scenarios depicting an interaction between a police officer and a motorist. The scenes were identical except that the race of the motorist and the officer were varied. After viewing the videotaped scenario, the research participants were asked to rate the interaction. The results indicated that African Americans and Whites view the delivery of justice very differently. African Americans judged the police officers to be less impartial and more prejudiced than Whites. It will be useful to further explore these issues to better understand the potential impact of these negative feelings on important justice matters. PMID- 11787073 TI - Women in danger: intimate partner violence experienced by women who qualify and do not qualify for a protective order. AB - Not all women who apply qualify for a civil protective order. This study compares the type and severity of violence reported by women who qualified with that experienced by women who did not qualify. Ninety women seeking a protective order against a male intimate were interviewed. Findings indicated that 28% of women applying for a protective order did not qualify primarily because of cohabitation requirements or childbearing status. Actual and threatened violence was measured with the 46-item Severity of Violence Against Women Scale. A 17-item questionnaire measured stalking behavior. Levels of reported violence for the preceding 3 months were measured for the two groups. The symbolic threat behavior only of throwing, smashing, or breaking an object was significantly higher for qualifying women. The physical abuse behavior only of being pushed, shoved, or pulled was significantly higher. None of the stalking behaviors were significantly different. Data are urgently needed that document the barriers to abused women receiving protective orders, the relevancy of qualifying criteria, and the effectiveness of protective orders issued. PMID- 11787075 TI - The application of an action system model to destructive behaviour: the examples of arson and terrorism. AB - This article argues that criminal and deviant behaviour can be productively viewed through an action system framework. The idea is developed by considering two forms of destructive behaviour: arson and barricade-hostage terrorist incidents. Two studies are presented. The first study tests the hypothesis that different forms of arson will reflect the four dominant states that an action system can take; integrative, expressive, conservative, and adaptive. A smallest space analysis was performed on 46 variables describing 230 cases of arson and the results identified the four themes of action system functioning. An examination of the personal characteristics of the arsonists also produced four variable groupings and a combined analysis of the four action scales and four characteristics scales also supported the structural hypothesis of the action system model. The second study applied the action system model to the study acts of terrorist barricade-hostage incidents. A smallest space analysis of 44 variables coded from 41 incidents again revealed four distinct forms of activity, which were psychologically similar to the four modes of arson identified in study one. Overall, these two studies provide support for the appropriateness of the action system framework as a way of classifying different forms of deviant behaviour. PMID- 11787076 TI - Residential mental health assessment within Dutch criminal cases: a discussion. AB - In Dutch criminal cases in which doubts arise about the defendant's mental health, a forensic assessment will be requested. This is provided either by the multidisciplinary staff of residential clinics who conduct forensic evaluations for the court, or by mental health professionals contracted on a part-time basis by district courts. This article discusses the procedures applied in such cases as well as the relevant legal provisions. It focuses particularly on the clinical observation, evaluation, and reporting that is carried out over a number of weeks in the residential setting of the Pieter Baan Centrum. Specific attention is paid to procedures applied in this clinic. It is suggested that Dutch procedures for the use of mental health expertise can best be characterized by three aspects: multidisciplinary observation and reporting, the use of a sliding scale for indicating degree of responsibility, and, finally, the involvement and payment of experts by the state as such, rather than by the prosecution and/or the defense. PMID- 11787077 TI - Neonaticide: an appropriate application for therapeutic jurisprudence? AB - Might therapeutic jurisprudence, a perspective that attempts to study interaction between the legal and mental health disciplines, be brought to bear effectively with respect to neonaticide, the murder of a newborn infant in the first 24 hours of its life? This is a crime that leads to sentencing that is now rarely therapeutic, rehabilitative, or corrective. An examination of the crime, its motives, and its perpetrators precedes a discussion of ways in which the mental health viewpoint in this matter might be brought to the active attention of the courts in order to promote sentencing that is appropriate to both the crime and the transgressor. PMID- 11787079 TI - Preparing to treat prions. PMID- 11787080 TI - Studies on shingles, is the virus ordinary chickenpox virus? PMID- 11787081 TI - Generation of influenza A virus from cloned cDNAs--historical perspective and outlook for the new millenium. AB - Influenza virus reverse genetics has reached a level of sophistication where one can confidently generate virus entirely from cloned DNAs. The new systems makes it feasible to study the molecular mechanisms of virus replication and pathogenicity, as well as to generate attenuated live virus vaccines, gene delivery vehicles, and possibly other RNA viruses from cloned cDNAs. During the next decade, one can anticipate the translation of influenza virus reverse genetics into biomedically relevant advances. PMID- 11787082 TI - Mechanistic aspects of HIV-1 reverse transcription initiation. AB - During reverse transcription, the positive-strand HIV-1 RNA genome is converted into a double-stranded DNA copy which can be permanently integrated into the host cell genome. Recent analyses show that HIV-1 reverse transcription is a highly regulated process. The initiation reaction can be distinguished from a subsequent elongation reaction carried out by a reverse transcription complex composed of (at least) heterodimeric reverse transcriptase, cellular tRNA(lys3) and HIV-1 genomic RNA sequences. In addition, viral factors including Tat, Nef, Vif, Vpr, IN and NCp7, cellular proteins, and TAR RNA and other RNA stem-loop structures appear to influence this complex and contribute to the efficiency of the initiation reaction. As viral resistance to many antiretroviral compounds is a continuing problem, understanding the ways in which these factors influence the reverse transcription complex will likely lead to novel antiretroviral strategies. PMID- 11787083 TI - HHV-8 infection: a model for reactivation and transmission. AB - The rapid pace of knowledge about HHV-8 since its discovery has been one of the most exciting aspects of medical virology in the last decade. As outlined in this review, the discovery by Drs Chang and Moore of this virus has opened up a broad field of biology with interesting contrasts between current epidemiological data for Kaposi's sarcoma and the cell biology of this gamma herpesvirus. In particular, we summarise the paucity of virological data supporting genital sites of replication and emphasise detection of HHV-8 in the oropharynx. Hopefully continued study will address many of the critical questions that exist today regarding how this infection is transmitted and acquired. PMID- 11787084 TI - [Chinese medicinal herbs can be insidious for the liver]. PMID- 11787085 TI - [Patients on the street--is out-patient care functioning in Finland?]. PMID- 11787086 TI - [Can liver tolerate chinese medicinal herbs?]. PMID- 11787087 TI - [The role of the intestinal immune system in the etiology of type 1 diabetes]. PMID- 11787088 TI - [Spontaneous splenic rupture]. PMID- 11787089 TI - [Duodecim books can be bought at the Finnish Book shop for membership price]. PMID- 11787090 TI - [The shadows of the soul--and then what?]. PMID- 11787091 TI - [New methods of functional brain imaging]. PMID- 11787092 TI - [Defining the epileptogenic focus]. PMID- 11787093 TI - [Functional brain imaging in psychiatry]. PMID- 11787094 TI - [Functional imaging of cerebrovascular disorders]. PMID- 11787095 TI - [Functional imaging of brain tumors]. PMID- 11787096 TI - [Auditory event related brain potentials in the research of brain development and its disorders]. PMID- 11787097 TI - [Children's language disorders from the point of view of brain research--dyslexia as an example]. PMID- 11787098 TI - [Removal of cholesterol from the cells--a new solution to fat diseases?]. PMID- 11787099 TI - [Fall-induced injuries among the elderly are a big challenge of the 21st century]. PMID- 11787100 TI - [What is the impact of genetic factors in anxiety-related traits?]. PMID- 11787101 TI - [Inheritance of alcohol dependence]. PMID- 11787103 TI - [Blood vessel catheter-associated infections]. PMID- 11787102 TI - [Obesity and female reproductive health]. PMID- 11787104 TI - [Is it possible to prevent kidney problems caused by immunosuppression?]. PMID- 11787105 TI - [Rewarming the severely hypothermic patient with the help of heart-lung machine]. PMID- 11787106 TI - [Treatment of trichomoniasis--what if nitroimidazoles do not suit the patient?]. PMID- 11787107 TI - [Diagnostics and treatment of helicobacter infection. Treatment recommendation from Finnish Gastroenterological Association]. PMID- 11787108 TI - [A newly found cause for sudden cardiac death]. PMID- 11787109 TI - [When are new antineoplastic drugs needed?]. PMID- 11787110 TI - [How to reduce the risk of suicide in a schizophrenic patient?]. PMID- 11787111 TI - [Hereditary polymorphic ventricular tachycardia as a cause of syncopes and sudden cardiac deaths]. PMID- 11787112 TI - [Complete atrioventricular block in a fetus and in a newborn]. PMID- 11787113 TI - [Diagnostics and treatment of Lyme borreliosis]. PMID- 11787115 TI - [Eggs and cholesterol--was the message of the editorial correctly interpreted?]. PMID- 11787114 TI - [Drug regulatory agency comments on the editorial about the new influenza drugs]. PMID- 11787116 TI - [Changed law about radiation since January 1st 2000]. PMID- 11787117 TI - [Responsibilities of the referring doctor and the radiologist]. PMID- 11787118 TI - [Magnitude and units of radiation and radioactivity and estimating the dosage]. PMID- 11787119 TI - [Adverse effects of ionizing radiation]. PMID- 11787120 TI - [Patient radiation doses in X-ray and isotope investigations]. PMID- 11787121 TI - [New regulations to guide the medical use of radiation]. PMID- 11787122 TI - [To whom can information about investigations exposing to radiation be given?]. PMID- 11787123 TI - [Good bad sun]. PMID- 11787124 TI - [Diagnosis of brain death]. PMID- 11787125 TI - [Hematuria]. PMID- 11787126 TI - [Hereditary hemochromatosis]. PMID- 11787127 TI - [Juvenile rheumatoid arthritis]. PMID- 11787128 TI - [Promises, disappointments and possibilities of screening tests]. PMID- 11787129 TI - [Either or]. PMID- 11787130 TI - [Keys to our fate in genetic testing?]. PMID- 11787131 TI - [Possibilities and problems of screening in the maternal health services]. PMID- 11787132 TI - [Screening of infectious diseases]. PMID- 11787133 TI - [Screening for cancer still useful and effective]. PMID- 11787134 TI - [When is screening economically beneficial?]. PMID- 11787135 TI - [Risks and adverse effects of genetic screening]. PMID- 11787136 TI - Molecular biology of fertilization. AB - Our understanding of molecular mechanisms of fertilization in mammals has lagged behind the rapid development of reproductive technology over the last decade. Significant advances in knowledge have resulted mainly from studies in laboratory animals in vitro. However, this situation has changed in the last few years as targeted mutagenesis in mice has provided important new information about genes and proteins involved in basic aspects of sperm-egg interactions in vivo. In this brief review the current knowledge about the generic aspects of mammalian fertilization is summarized, together with particular features of reproductive physiology related to cats and dogs. PMID- 11787137 TI - Role of changes in the pulsatile secretion pattern of FSH in initiation of ovarian folliculogenesis in bitches. AB - The results of two studies in which the pulsatile secretion patterns of LH and FSH were investigated in six Beagle bitches during early, mid- and late anoestrus and in six anoestrous Beagle bitches treated with bromocriptine are summarized to improve our knowledge of the endocrine changes that lead to a new follicular phase in bitches. Blood samples for the determination of secretory profiles were obtained via jugular venepuncture at 10 min intervals for 6 h. In untreated bitches, blood samples were collected during early, mid- and late anoestrus. In bromocriptine-treated bitches (20 micrograms kg-1 twice each day, starting 100 days after ovulation until the start of the next oestrous cycle), blood samples were collected before treatment and at 2 week intervals after the start of bromocriptine treatment until the next ovulation. In all bitches, FSH and LH were secreted in a pulsatile manner and FSH pulses coincided with LH pulses. Progression from early to late anoestrus was associated with an increase in FSH secretion without a concomitant increase in LH secretion. The bromocriptine induced shortening of the interoestrous interval was also associated with an increase in FSH secretion without a concomitant increase in LH secretion. These results indicate that in bitches an increase in circulating FSH should be considered to be a critical event required for the initiation of ovarian folliculogenesis and consequently the termination of anoestrus. PMID- 11787138 TI - Manipulation of canine fertility using in vitro culture techniques. AB - Highlighting the important aspects of canine reproductive physiology, this review documents developments made with in vitro culture of canine gametes, and indicates how these techniques can be further exploited. In vitro culture of gametes and embryos has been achieved in many mammalian species, allowing the development of reproductive technology. Despite numerous investigations in other species, only a small number have been performed in dogs. Further studies are required to establish the differences between canine reproductive physiology and that of other mammals. Ultimately, these studies may lead to the development of a gamete salvage technique incorporating oocyte, spermatozoa and embryo culture, and cryopreservation to allow genetically important material from Canidae to be saved. In dogs, the oocyte is ovulated when immature rather than mature, as in other species, and the survival rate of spermatozoa is greater within the female tract. By incorporating knowledge of canine reproductive physiology and work on in vitro culture in other mammals, some important achievements have been made. Sperm capacitation, induction of the acrosome reaction, maturation of canine oocytes and fertilization have all been achieved in vitro. Embryo culture has proven more difficult, with only two studies reporting success. Cryopreservation of spermatozoa has been perfected and is used routinely when transporting semen for artificial insemination. However, improvement in embryo culture techniques and development of oocyte and embryo freezing are required. This work in the domestic model may lead to development of a gamete-banking programme to safeguard the future of endangered canine species. PMID- 11787139 TI - Test of canine sperm function in vitro using primary homologous oocytes with fluorescence and confocal microscopy. AB - In vitro capacitated canine spermatozoa can interact with both mature and immature homologous oocytes in vitro, but it is difficult to determine whether spermatozoa have actually penetrated the oocyte or have simply bound to the zona pellucida. The aim of the first part of this study was to determine accurately the location of spermatozoa in relation to the oocyte by comparing observations made using confocal and fluorescence microscopy. The fluorescence technique had a sensitivity of 66%, and correctly identified 98% of the spermatozoa that had penetrated or bound oocytes and could discriminate between penetrated and bound spermatozoa with a sensitivity and specificity of 97% and 100%, respectively. This finding demonstrates that evaluation of the assay by fluorescence microscopy is reliable for detecting the presence and location of spermatozoa in relation to homologous oocytes. The aim of the second part of the study was to attempt to simplify the assay using fluorescence microscopy and immature oocytes. No significant difference was found between sperm interaction with mature and immature oocytes, which demonstrates that culturing oocytes before the assay has no benefit, and that the assay can be performed quickly and easily using non cultured oocytes to provide rapid evidence of the fertilizing potential of spermatozoa. PMID- 11787140 TI - Zona pellucida binding assay--a method for evaluation of canine spermatozoa. AB - The present study describes the use of a zona pellucida binding assay for the evaluation of canine spermatozoa. A zona pellucida binding assay is a sperm evaluation test that is practical to perform and provides potentially useful information on the damage caused to spermatozoa by new methods of sperm storage. The addition of the detergent Equex STM paste to the cryopreservation extender has a positive effect on the zona pellucida binding capacity of cryopreserved spermatozoa. A large number of sperm-oocyte complexes need to be evaluated because of the variability in sperm binding capacity among oocytes. However, this does not constitute a major problem as canine oocytes can be stored before use in a zona pellucida binding assay and sperm-oocyte complexes can be fixed and stored until evaluation. PMID- 11787141 TI - Influence of different stages of the oestrous cycle on cumulus-oocyte communications in canine oocytes: effects on the efficiency of in vitro maturation. AB - The aim of this study was to investigate the effects of different stages of the oestrous cycle on the communications between dog oocytes and cumulus cells, as well as their possible relationships with the meiotic competence of oocytes matured in vitro. Ovaries were harvested from bitches undergoing anoestrus or late pro-oestrus. Maturation of cumulus-oocyte complexes (COCs) was performed in TCM-199 with 0.3% (w/v) BSA, 0.5 iu FSH ml-1 and 0.5 iu LH ml-1 for 72 h. At the time of collection (0 h), and after 24, 48 or 72 h of culture, some oocytes were stained with Lacmoid to evaluate the nuclear stage of maturation. At 0, 24 or 48 h of in vitro maturation (IVM), oocytes were microinjected (n = 84) with a 3% (w/v) Lucifer yellow solution to evaluate the presence of cumulus-oocyte communications through gap junctions. At t = 0, communications were open in 89% of COCs collected during late pro-oestrus, whereas such communications were not evident in any of the oocytes collected during anoestrus. Communications remained permeable for the first 24 h of maturation in many late pro-oestrous oocytes (67%), whereas no fluorescence diffusion was observed at 48 h of maturation. The presence of cumulus-oocyte communications in late pro-oestrous oocytes was accompanied by their ability to resume meiosis and reach telophase I or metaphase II at higher rates than in oocytes collected during anoestrus (11.1% versus 0%, respectively; P < 0.01). These results indicate that, during anoestrus, there are no permeable gap junctions between oocytes and surrounding cumulus cells at the time of isolation from the ovary. This finding indicates that such oocytes are unsuitable for IVM, as confirmed by their inability to reach telophase I or metaphase II in culture. In contrast, a positive correlation was observed between the presence of permeable gap junctions and meiotic competence in COCs isolated at late pro-oestrus. However, the small proportion of oocytes reaching telophase I and metaphase II indicates that further efforts to define better culture conditions are still required. PMID- 11787142 TI - In vitro maturation of bitch oocytes: effect of sperm penetration. AB - In contrast to most mammals, bitches ovulate immature oocytes at the germinal vesicle stage. Spermatozoa can be present in the oviduct of bitches at ovulation. The aim of this study was to investigate the influence of premature fertilization on the resumption of meiosis. In addition, the relative behaviour of male and female chromatin was observed. Canine cumulus-oocyte complexes cultured in medium 199 supplemented with 20% fetal calf serum for 24 h were incubated in vitro in the presence or absence of fresh dog semen for 24 h, and then rinsed and cultured in the same medium for a further 24 h. Chromatin was stained by propidium iodide and all oocytes were examined under laser scanning confocal microscopy. Results show that sperm penetration can occur in vitro in immature oocytes and that this induces a resumption of meiosis: at 72 h, the percentage of oocytes at the germinal vesicle stage decreased significantly and the percentage of oocytes beyond metaphase I increased. However, premature fertilization was ineffective for 40% of oocytes, which remained at the germinal vesicle stage. Measurement of chromatin areas in fertilized oocytes showed an overall parallel condensation decondensation of both female and male chromatin from the germinal vesicle stage to the pronuclear stage, indicating that male and female chromatins are sensitive to the same cell cycle regulators. PMID- 11787143 TI - FSH secretion patterns during pregnant and nonpregnant luteal periods and 24 h secretion patterns in male and female dogs. AB - The aim of this study was to investigate the secretion patterns of FSH: (i) during the canine oestrous cycle with particular attention to the luteal period; and (ii) during 24 h in male and female dogs. Plasma FSH concentrations were measured by a highly specific homologous canine immunoradiometrical (IRMA) assay using monoclonal antibodies specific for canine FSH. In the first study, FSH concentrations were measured daily from +/- 15 days before until 150 days after the LH surge in groups of pregnant (n = 5) and nonpregnant (n = 5) Beagle bitches. Day 0 of the cycle was the day of the preovulatory LH peak as measured by LH radioimmunoassay. In the second study, FSH concentrations were measured at 1 h intervals for 24 h in five bitches at day 120 after the LH surge and in five males. From day 35 to day 40 after the LH peak, FSH concentrations were higher in pregnant than in nonpregnant luteal phases. A significant and abrupt decrease in FSH concentrations was observed at about the time of parturition (day 65) and was followed by lower FSH concentrations during lactation compared with nonpregnant bitches. FSH concentrations in nonpregnant animals were fairly constant from the end of oestrus to mid-anoestrus. In both post-lactation and anoestrous bitches, plasma concentrations of FSH increased consistently as anoestrus progressed. No significant differences in the mean hour-to-hour patterns of FSH secretion were observed over 24 h and no differences were detected between male and female dogs. However, a clear pulsatile pattern of secretion was observed in all individuals, both males and females, with an apparent 4.8 h interval between peaks. The results of this study demonstrate major differences in FSH secretion between pregnant and nonpregnant bitches. This finding indicates that there are differences in the regulation of the hypothalamo-pituitary-ovarian axis during pregnancy, possibly related to changes in activity of the corpus luteum. The results of this study also demonstrate a pulsatile pattern of FSH secretion in both male and female bitches, with a 4.8 h interval between peaks, and confirms the progressive increase in plasma FSH concentrations observed during anoestrus. PMID- 11787144 TI - Effect of technical settings and semen handling upon motility characteristics of dog spermatozoa measured using computer-aided sperm analysis. AB - Technical aspects of computer-aided sperm analysis and the influence of semen preparation were investigated for their effect on the measured motility characteristics of dog spermatozoa. Altering the internal image settings significantly influenced the measured motility by changing the ability of the computer to recognize spermatozoa. Similarly, the use of a longer minimum track point (the minimum length of sperm track detected before analysis) resulted in failure to detect some of the faster moving spermatozoa. There was a clear interaction between the search radius (the threshold distance below which objects are linked together) and the minimum track point. A 1 min analysis period was required to eliminate reduced motility as a result of sample deterioration upon the microscope stage. The dilution of semen to between 1:10 and 1:20 was necessary to allow accurate detection of sperm motility; however, such dilution significantly altered the motility characteristics of spermatozoa. The influence of viscosity and ionic composition of the media was confirmed by comparing dilution in seminal plasma with dilution in iso-viscous methylcellulose and iso osmotic saline, respectively. Analysis temperature had a significant influence on sperm motility, although values were most constant within the range of 25-45 degrees C. Extremes of temperature had marked deleterious effects. Careful selection of internal image settings, the minimal track point and search radius, and the analysis time are essential for accurate detection of sperm motility. Moreover, dilution of spermatozoa per se, and dilution with media of different viscosities and ionic compositions can alter the sperm motility. Once these aspects of computer image analysis are determined for each system, the method can achieve a high degree of repeatability with interanalysis coefficients of variation of < 12%, and intra-analysis coefficients of variation of < 3% for most parameters. PMID- 11787145 TI - Maturation and fertilization of blue fox (Alopex lagopus) oocytes in vitro. AB - The aim of the present study was to assess the progression of meiotic maturation and fertilization of in vitro matured blue fox (Alopex lagopus) oocytes at different time intervals after in vitro maturation and insemination by the use of confocal laser scanning microscopy. A total of 242 immature oocytes from ovarian follicles 1-2 mm in diameter from seven ovulating blue fox vixens at oestrus were cultured for 48 h in TCM-199 before in vitro insemination with 5.0 x 10(5) frozen thawed fox spermatozoa. Oocytes were transferred to 50 microliters microdroplets of modified Tyrode's medium without glucose at pH 7.7 under mineral oil, inseminated and cultured at 38 degrees C in a humidified atmosphere with 5% CO2 for 2 (n = 10), 4 (n = 22), 8 (n = 41), 20 (n = 52), 24 (n = 10), 30 (n = 48) and 48 h (n = 59). The oocytes and zygotes were stained with propidium iodide and were analysed by confocal laser scanning microscopy or epifluorescence microscopy. Only 125 of 242 oocytes (52%) could be evaluated: of these germinal vesicle breakdown (GVBD) was observed in five of nine oocytes (56%) at 2 h, eight of 18 oocytes (44%) at 4 h, eight of 18 oocytes (44%) at 8 h, 27 of 42 oocytes (64%) at 20-24 h, 14 of 19 oocytes (74%) at 30 h, and 13 of 19 oocytes (68%) at 48 h after insemination. In total, 75 of 125 oocytes (60%) underwent GVBD. All stages from the germinal vesicle to the four-cell stage embryos were observed, but the rate of cleavage was low (9%). Immature oocytes collected from small subordinate ovarian follicles of oestrous vixens after ovulation of the dominant follicles were able to mature and be fertilized, as well as undergo the first two cleavage divisions in vitro. PMID- 11787146 TI - Embryo development, hormonal requirements and maternal responses during canine pregnancy. AB - The events of canine gestation appear to occur consistently among bitches relative to the time of the preovulatory LH surge. The interval from fertilization to the eight-cell stage was 5 days after insemination before oocyte maturation and only 3 days following insemination after oocyte maturation. Sixteen-cell embryos were observed at day 11 (day 0 = day of the LH surge) after either early or late insemination. Apparently, embryonic cleavage between the two cell and 16-cell stages occurs more rapidly after fertilization of more mature oocytes. This finding, together with the narrow window for fertilization, may explain why the duration of gestation is similar whether mating occurs before or a few days after oocyte maturation. Observations also indicate that cessation of migration and final situating of embryos occurs between day 16 and day 20 and that uterine lumen vesicles are > 1 mm in diameter at days 17-19; vesicles are > 2 mm in diameter and elongated to 3-6 mm by days 20-22. Some blastocyst enlargement occurs between day 14 and day 20, and expansion inside lemon-shaped uterine vesicles prevents flushing of intact embryos from the uterus after day 20 or 21. Blastocysts can be enclosed in the zona pellucida as late as day 19 and loss of zona pellucida with further expansion occurs on days 19-20. Uterine swellings can be observed in vivo, albeit inconsistently, at days 21-22 at the time of embryo attachment, and even before invasion of the embryo into the endometrium. The uterine responses to embryo localization may be detected via uterine transillumination by day 21, even in the absence of gross swelling. Blastocysts remain unattached as late as days 21-22; invasion of placental trophectoderm occurs as early as day 22 and as late as day 23, and only 1-2 days before heartbeats are detected by sonography. Assay of canine relaxin by canine relaxin-specific radioimmunoassay detected increases in serum relaxin concentrations as early as days 26-30 and no earlier than the concurrent increase in serum prolactin concentrations at days 26-30; the increase in serum relaxin concentrations was also no earlier than increases in the concentrations of serum acute phase proteins, including fibrinogen. It is not known whether relaxin can stimulate prolactin secretion in dogs. When natural progesterone alone was provided by injection and subcutaneous implants before and after ovariectomy performed before implantation, implantation occurred normally, and pregnancy was maintained to term. The increase in prolactin was not different from that of control pregnancy, despite the absence of effective systemic concentrations of oestrogen, as observed by a typical castration response in LH and FSH. Lack of oestrogen may have compromised mammary development and lactation. Therefore, the pregnancy-associated increase in prolactin concentrations does not require an increase in or the presence of maternal oestrogen. These observations extend our knowledge of canine pregnancy and indicate several areas worthy of further investigation. PMID- 11787147 TI - Embryonic developmental stages in relation to the LH peak in dogs. AB - Blood samples were collected from nine Beagle bitches every 6 h during pro oestrus and oestrus to measure plasma concentrations of progesterone, oestradiol and LH. The number of ovarian follicles was estimated once a day using transcutaneous ultrasonography. According to the concentrations of plasma progesterone, the bitches were mated once and subsequently ovariohysterectomized 3-7 days after mating. The number of corpora lutea was counted, and oocytes and embryos were collected by flushing of the oviducts. In ovaries that had more than three follicles, the number of follicles observed using ultrasonography was underestimated, whereas the recovery rate (number of oocytes and embryos flushed/number of corpora lutea counted) was 99%. Embryos were processed for sectioning and the developmental stages were determined by counting the number of blastomeres under bright field microscopy. Potentially fertilized oocytes and a zygote were observed on day 7 after the LH peak and the developmental rate was about one cell cycle in 24 h until day 12 after the LH peak. The timing of embryonic development was significantly correlated with the time of the LH peak. PMID- 11787148 TI - Circulating relaxin concentrations in pregnant and nonpregnant bitches: evaluation of a new enzymeimmunoassay for determination of pregnancy. AB - A new kit (ReproCHEK RELAXIN) intended for the diagnosis of pregnancy in bitches is now available for veterinary use. This assay measures relaxin concentrations in plasma and whole blood samples, and the presence of significant amounts of relaxin is indicative of pregnancy. A clinical trial was carried out to evaluate the performance of the test. Serial blood samples were collected on alternate days, and relaxin concentrations were determined from day 15 to day 35 after the LH surge (estimated by progesterone concentrations). Pregnancy was confirmed using ultrasonography. At the end of pregnancy, both the day of whelping and the size of the litter were recorded. Pregnancy was established in 61 bitches. The day that pregnancy was detected using the relaxin assay ranged from day 19 to day 28 after the LH surge and had a mean (+/- SD) of 25.4 +/- 2.5 days. The day of parturition was taken as a reference point, and pregnancy was detected from -46 to -38 days (mean -40.2 +/- 2.4 days) before parturition. False positives were not observed in pseudopregnant bitches (n = 16) or in the control group (30 anoestrous and ten unmated bitches). These results demonstrate that the new assay kit is an inexpensive, user-friendly and reliable technique for determining pregnancy. PMID- 11787149 TI - Influence of litter size and breed on the duration of gestation in dogs. AB - The variation in the duration of gestation, defined as the period from mating to parturition, was studied in 113 bitches of six breeds (31 Dobermans, 31 Labrador retrievers, 14 German shepherds, 13 Bernese mountain dogs, 12 golden retrievers and 12 West Highland white terriers). The bitches were mated once on the optimal day for mating, which was established by measuring the plasma concentration of progesterone. The duration of gestation varied between 58 and 65 days with a mean of 61.4 +/- 1.5 days (+/- SD). The mean duration of gestation in West Highland white terriers (62.8 +/- 1.2 days) was significantly longer than that of German shepherds (60.4 +/- 1.7; P < 0.001), Labrador retrievers (60.9 +/- 1.5; P < 0.001) and Dobermans (61.4 +/- 1.0; P < 0.025). The variation in the duration of gestation in any one of the six breeds was low, ranging from 4 to 7 days, or less when litters of one pup (n = 4) were excluded. The number of pups per litter varied between one and 15 with a median of eight pups. In the total population, the duration of gestation was negatively correlated with litter size (r = -0.73; P = 0.005) for litters (n = 112) containing < or = 13 pups. However, within each breed multiple regression analysis failed to show any influence of litter size on the duration of gestation. The median litter size of different breeds and the mean duration of gestation were negatively correlated (r = -0.78; P = 0.03; n = 6). Therefore, although it was not conclusively proven, the results indicate that the breed is a major determinant of the duration of gestation in bitches and that the influence of breed may be ascribed to breed-related differences in litter size. PMID- 11787150 TI - Characterization of trophoblast cell populations by lectin histochemistry in canine placenta during development. AB - The aim of this study was to identify and characterize populations of trophoblast cells in canine placenta during different stages of fetal development using lectin histochemistry. Dogs have endotheliochorial placentation and trophoblast cell invasion continues after chorioallantois villous penetration early in pregnancy, leading to formation of a labyrinth. Specialized subpopulations of cells differentiate, such as syncytial trophoblast that invades the maternal epithelium early in placentation and surrounds and forms intimate cuffs around maternal blood vessels. Marginal haematomata, which are lined by specialized phagocytic cytotrophoblast cells, form by mid-gestation. Invasive 'extravillous' cells advance into and remodel maternal endometrial tissues further. Placentas and attached uterine tissues were collected and sampled from six bitches at mid gestation (days 31-33 of gestation) and 12 females in late gestation (day 42 term) for characterization of these tissues and identification of other populations of trophoblast cells. Uterine tissues from nonpregnant bitches were also collected at oestrus (n = 2) and during the luteal phase (n = 1). In histochemical studies, two of six biotinylated lectins that were tested stained cytotrophoblast and syncytial trophoblast cell populations differentially. Arachis hypogaea agglutinin (PNA) was specific for cytotrophoblasts in placental tissue lining villi and cytotrophoblastic cells with phagocytic or absorptive phenotypes in the necrotic zone at mid-gestation. In late gestation, cytotrophoblast cells with an absorptive phenotype at the interface between the labyrinth and lacunar glandular chambers were stained with PNA. Staining of other cells was minimal, with the exception of deep endometrial glands. Lectin binding using Maclura pomifera agglutinin (MPL) specifically stained the same cells as PNA and the population of invasive syncytial trophoblast cells remodelling maternal blood vessels and small maternal vessels at the materno-fetal interface, as well as trophoblast cells within necrotic zones at mid-gestation. Both lectins were positive for phagocytic cytotrophoblast cells lining the haematophagus organs. The results of this study demonstrate that lectin histochemistry is a useful tool for staining subpopulations of cytotrophoblast and syncytial trophoblast cells. PMID- 11787151 TI - Investigation of the fibrinolytic system during nonpregnant and pregnant oestrous cycles of bitches. AB - The fibrinolytic system was studied during the oestrous cycle of nonpregnant (n = 12) and pregnant (n = 12) bitches. Blood samples were taken during late pro oestrus, at ovulation, at days 1, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90 and 120 of metoestrus, and during anoestrus. The concentrations of fibrinogen and fibrin(ogen) degradation products, the euglobulin lysis time, the activities of plasminogen and alpha 2-plasmin inhibitor and the haematocrit were determined. Concentrations of oestradiol and progesterone were measured in additional blood samples in late pro-oestrus, at ovulation, at days 30, 60, 90 and 120 of metoestrus, and in anoestrus, for retrospective control of oestrous cycle stages. In the pregnant bitches, significantly higher values (P < 0.05) were found for the concentrations of fibrinogen and fibrin(ogen) degradation products from day 15 to day 60, for the euglobulin lysis time from day 20 to day 50, for the plasminogen activity from day 15 to day 40 and for the alpha 2-plasmin inhibitor activity from day 20 to day 30 of metoestrus compared with values for nonpregnant bitches. The significant increase in fibrinogen concentrations observed in the pregnant bitches is thought to be a local reaction of the coagulation system due to alterations of the uterine epithelium and endothelium induced by placentation. The slight increase in the concentration of fibrin(ogen) degradation product combined with the slight increase in the activities of plasminogen and alpha 2 plasmin inhibitor are indicative of a local rather than systemic hyperfibrinolysis during canine pregnancy. The prolonged euglobulin lysis time, which is indicative of decreased fibrinolytic activity in pregnancy, is thought to be a laboratory artefact caused by increased fibrinogen concentrations. PMID- 11787152 TI - Diagnosis of canine fetal health by ultrasonography. AB - The detection of fetal pathology is important for the care of puppies in the postnatal period. The objective of this study was to identify parameters of fetal distress by determining fetal heart rate and bowel movements, and also to detect early pathology by means of fetal biometry, which involves determination of the biparietal and abdominal diameters. Ultrasonographic examinations were carried out on 30 pregnant bitches of different breeds and ages at least three times, including examination at days 40-47, days 48-57, and days 58-62 after coitus, and subsequently every 12-14 h for 3 days before parturition. Fetuses that had biparietal:abdominal diameter ratios of < 2 at the second and third series of ultrasonography, or after birth were considered to have intrauterine growth retardation. The average weight of each litter was calculated and puppies that weighed < 20% of the average weight were also considered to have experienced intrauterine growth retardation. Intrauterine growth retardation occurred in 39.6% of the bitches studied. Fetuses were considered to be normal when heart rate, determined by a Doppler flowmeter was > 220 beats min-1; suffering from slight fetal distress when heart rate was between 180 and 220 beats min-1; suffering from severe fetal distress when heart rate was < 180 beats min-1. Some level of distress was observed in 33.0% of puppies. In 86.7% of bitches, bowel movements were observed in at least one puppy, and appeared to be correlated with fetal distress. Bowel movements were observed in all of the puppies that had severe fetal distress (heart rate < 180 beats min-1), whereas bowel movements were observed in only 40.0% of puppies with slight fetal distress (heart rate 180 200 beats min-1). In conclusion, ultrasonographic evaluation allowed identification of fetuses with intrauterine growth retardation, and bowel movements were a reliable indicator of fetal distress; these conditions are presumed to indicate a greater perinatal risk. PMID- 11787153 TI - Early-age neutering of dogs and cats in the United States (a review). AB - Prepubertal gonadectomy, often referred to as early-age neutering, has increased in popularity in the United States. The procedure is often used at animal care and control facilities, where puppies and kittens are neutered as early as 7 weeks of age or before adoption. Although the anaesthetic and surgical procedures appear to be safe, studies continue to evaluate the long-term effects on health and behaviour. Early-age neutering is one technique that is used to combat pet overpopulation, a problem whereby millions of unwanted healthy dogs and cats are euthanased each year. Although neutering animals is helpful in controlling pet overpopulation, other factors must be considered. In addition, many animals are relinquished to shelters when they show inappropriate behaviours, because owners and veterinarians are unable to modify animal behaviour. This review discusses early-age neutering in the United States, and includes the review of scientific studies that have evaluated this procedure in puppies and kittens. Early-age neutering does not stunt growth in dogs or cats (a once-held belief), but may alter metabolic rates in cats. The anaesthetic and surgical procedures are apparently safe for young puppies and kittens; morbidity is lower and recovery is faster than in adult animals. To date, adverse side effects are apparently no greater in animals neutered at early ages (7 weeks) than in those neutered at the conventional age (7 months). PMID- 11787154 TI - Timing and location of zona pellucida synthesis during oogenesis in domestic cats -an ultrastructural immunohistological investigation. AB - The application of zona pellucida proteins for contraception of wildlife and feral animals, including stray cats, has been promoted since it was demonstrated to be effective for free-roaming feral mares. Active immunization with zona pellucida proteins leads to either reversible or irreversible infertility. Therefore, knowledge of the timing and location of zona pellucida synthesis during oogenesis in cats is a key aspect of designing an immunocontraceptive for felids. Domestic cat ovaries obtained after ovariohysterectomy were used to produce a specific rabbit antibody against feline zonae pellucidae. Ultrathin sections (70 nm) of cat ovaries were treated with the anti-zona antibody followed by incubation with gold-labelled anti-rabbit IgG for ultrastructural investigation. The gold label was related to the ultrastructure of oocytes and granulosa cells. Cat follicles at different stages of development were examined. The antibody reacted very specifically with zona pellucida proteins in fully grown oocytes with a compact zona pellucida. In secondary follicles, gold labels were found on the zona pellucida and inside granulosa cells in the vicinity of oocytes. Primary follicles were labelled inside their cubic granulosa cells and on fragments of zona pellucida in the cleft between granulosa cells and the oocyte. Some primordial follicles were characterized by labelling of the granulosa cells. In conclusion, these results indicate that cat zona pellucida is produced exclusively by granulosa cells and not by oocytes. Synthesis of zona pellucida takes place at every stage of follicular development. PMID- 11787155 TI - The relationship of urinary incontinence to early spaying in bitches. AB - It is still controversial whether a bitch should be spayed before or after the first oestrus. It would be desirable to spay bitches at an age that would minimize the side effects of neutering. With regard to the risk of mammary tumours, early spaying must be recommended because the incidence of tumours is reduced considerably. The aim of the present study was to determine whether early spaying also reduces the risk of urinary incontinence. The owners of 206 bitches that had been spayed before their first oestrus and for at least 3 years were questioned on the occurrence of urinary incontinence as a result of spaying. At the time of the enquiry the average age of the bitches was 6.5 years, and the average age at the time of surgery was 7.1 months. Urinary incontinence after spaying occurred in 9.7% of bitches. This incidence is approximately half that of spaying after the first oestrus. Urinary incontinence affected 12.5% of bitches that were of a large body weight (> 20 kg body weight) and 5.1% of bitches that were of a small body weight (< 20 kg body weight). The surgical procedure (ovariectomy versus ovariohysterectomy) had no influence on the incidence, or on the period between spaying and the occurrence of urinary incontinence. Urinary incontinence occurred on average at 2 years and 10 months after surgery and occurred each day, while the animals were awake or during sleep. However, compared with late spaying the clinical signs of urinary incontinence were more distinct after early spaying. PMID- 11787156 TI - Comparison of two protocols with a progesterone antagonist aglepristone (RU534) to induce parturition in bitches. AB - Parturition was induced in ten Beagle bitches by injecting them subcutaneously with 15 mg aglepristone kg-1 (Alizine) at day 58 of gestation and 24 h later and subsequently at 2 h intervals with either 0.08 mg alfaprostol kg-1 (Alfabedyl) (group 1; five bitches) or 0.15 iu oxytocin kg-1 (Ocytocine S) (group 2; five bitches). Blood samples were collected every 4 h until the end of parturition to assay plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in all bitches. The mean time of onset of parturition for both groups was not significantly different (32.6 +/- 3.7 h for group 1 versus 31.6 +/- 3.6 h for group 2), although the mean expulsion time for bitches from group 2 (4.5 +/- 1.8 h) was significantly shorter than that of bitches in group 1 (9.1 +/- 2.0 h). At birth, 93% of the pups were alive in group 2 compared with 86% in group 1. Peripheral plasma concentrations of progesterone increased significantly after the administration of aglepristone, but direct or indirect luteolysis was not induced, and plasma concentrations of oxytocin or cortisol did not change during the first 24 h after administration of aglepristone. PGFM concentrations increased significantly after 4 h of aglepristone administration. During the first 20 h after aglepristone administration, prolactin concentrations increased significantly. At parturition, bitches in group 2, which had the shorter expulsion time of pups, were characterized by significantly higher concentrations of oxytocin and PGFM than bitches in group 1. PMID- 11787157 TI - Hormonal variation in bitches after early or mid-pregnancy termination with aglepristone (RU534). AB - Seven bitches in early pregnancy (12.8 +/- 3.8 days after ovulation; group 1) and seven bitches in mid-pregnancy (32.0 +/- 1.53 days after ovulation; group 2) were used in this study. For each group, five bitches were treated with 0.10 mg aglepristone (Alizine) kg-1 and this dose was repeated 24 h later. Two control bitches received a placebo. Blood samples were collected at 6 h intervals to determine plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in the four control bitches. All bitches treated with aglepristone aborted. In group 1, embryonic death occurred; in group 2, fetal expulsion occurred 60-132 h after administration of aglepristone. After pregnancy termination, the interoestrous interval of aglepristone-treated bitches was significantly shorter than that before treatment. Treatment with aglepristone did not modify plasma concentrations of progesterone, prostaglandin, oxytocin or cortisol within 24 h after its administration, but it induced, in mid-pregnancy (group 2) a discharge of prolactin within 12 h after its administration. As an abortifacient, aglepristone acted on the uterus and, therefore, did not have direct or immediate luteolytic properties. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterized by an increase in the concentration of PGFM, but oxytocin and cortisol remained at basal concentrations. PMID- 11787158 TI - Control of reproduction with anti-progestin and oestrogens in captive bears. AB - The aim of this study was to establish new methods for controlling reproduction in bears. Anti-progestins were used to interrupt pregnancies. In two consecutive years, the anti-progestin J956 was administered to 11 female bears (nine Ursus arctos, one Ursus tibethanus, one Tremarctos ornatus) living in zoos. The anti progestin J956 was given orally (n = 4) or parenterally (n = 12). The anti progestin was administered alone or in combination with ethinyloestradiol, and before or after embryo implantation. The effects of anti-progestin treatment were determined using ultrasonographic examination of the urogenital tract and by monitoring progesterone concentrations in the blood and faeces. Oral administration of anti-progestin was not successful (successful in 0 of 4); however, in contrast, none of the parenteral treated animals remained pregnant (successful in 12 of 12). Parenteral treatment with J956, with or without ethinyloestradiol, was effective in disrupting pregnancy before implantation (successful in 6 of 6) and after implantation (successful in 6 of 6), but administration one month after implantation (n = 2) resulted in incomplete resorption of the fetuses. In conclusion, the administration of anti-progestins may be a useful method for preventing embryo implantation in captive bears. PMID- 11787159 TI - Use of a GnRH analogue implant to produce reversible long-term suppression of reproductive function in male and female domestic dogs. AB - Continuous low-dose administration of a GnRH analogue postpones oestrus in bitches and suppresses reproductive function in dogs. A new drug delivery formulation that could enhance the practicality of this approach for the control of reproduction has been developed. The objective of the present study was to determine whether this method of delivery could, by sustained release of the GnRH analogue deslorelin, act as a reversible anti-fertility agent in domestic male and female dogs for periods exceeding 1 year. Several long-term studies were performed, which monitored reproductive function in 30 dogs and 52 bitches. Suppression of reproductive function in male dogs was dose-related. Spermatogenesis was suppressed for more than a year in 14 of 16 dogs that received doses of > 0.25 mg deslorelin kg-1. In females, postponement of oestrus for periods of up to 27 months was observed, but there was no relationship between the stage of the oestrous cycle at the start of treatment and the duration of efficacy. Treatment-induced effects on fertility were reversible in both sexes. In summary, sustained release deslorelin implants were shown to elicit reversible long-term reproductive control in male and female domestic dogs. PMID- 11787160 TI - Suppression of the oestrous responses of bitches to the GnRH analogue deslorelin by progestin. AB - Studies were undertaken in Australia and Belgium to determine whether the initial pro-oestrous-oestrous responses of anoestrous bitches to treatment with deslorelin administered in a s.c. implant were inhibited by progestin treatment. Thirty-nine bitches of mixed breeding were treated daily with 2 mg megestrol acetate kg-1 body weight for 21 (group 1, n = 5) or 14 days (group 2, n = 10), or with 1 mg megestrol acetate kg-1 body weight for 14 days (group 3, n = 10). A deslorelin (6 mg) implant was placed s.c. on day 14 (group 1) or day 7 (groups 2 and 3) of treatment. Bitches not treated with progestin also received a deslorelin implant (group 4, n = 9) or were untreated controls (group 5, n = 9). Signs of pro-oestrus-oestrus were not observed in bitches in groups 1, 2 and 5, but were observed in bitches in groups 3 (4/10) and 4 (9/9). Four bitches in group 4 were mated, two of which became pregnant. The pregnancies failed at about day 40 of gestation and were associated with low plasma progesterone concentrations. Treatment with progestin inhibited the pro-oestrous-oestrous responses of bitches to deslorelin. PMID- 11787161 TI - Efficacy of the GnRH analogue deslorelin for suppression of oestrous cycles in cats. AB - The aim of this study was to develop a method for long-term but reversible inhibition of oestrous cycles in female cats by downregulation of GnRH receptors with deslorelin released from a long-acting implant. In a blind study with mature cats (n = 20), a 6 mg deslorelin implant was administered s.c. to ten cats and a placebo implant was administered to ten cats. Occurrence of oestrus and general health were observed daily, and individual faecal samples were collected at 3 day intervals for 14 months and analysed for oestradiol content. All the placebo treated queens continued to undergo normal oestrous cycles during the study. Oestrus was accompanied by peaks in oestradiol concentrations of > or = 20 ng g-1 faeces. Treatment with deslorelin initially stimulated oestradiol release, which accompanied treatment-induced ovulations. Thereafter, oestradiol concentrations decreased to 1-10 ng g-1 faeces and remained low for extended periods. Observations of small increases in oestradiol concentrations in one cat led to a second treatment with 6 mg deslorelin in five cats on day 155 after first treatment. Faecal oestradiol concentrations remained < 20 ng g-1 faeces in the five single treatment cats for 8.0, 8.5, 11.0 and 14.0 (two cats) months. Cats receiving two implants had the first oestradiol peak > 20 ng g-1 faeces after treatment at 7.5, 11.0 (two cats), 11.5 and 14.0 months. After 14 months, two cats had returned to normal cyclic activity, two had irregular small oestrogen peaks and six showed no cyclic activity. For months 2-5, 6-10 and 11-14, oestrogen values in treated cats were significantly different from control values (P < 0.001, 0.05 and 0.02, respectively). Differences in oestrogen concentration between control cats and cats that were treated twice were significant (P < 0.001) during months 6-10 only. The general health of treated cats was unchanged throughout the study. These results confirm that deslorelin can effectively suppress ovarian activity in domestic cats, but that the duration of suppression varies among individuals. PMID- 11787162 TI - Control of reproduction and sex related behaviour in exotic wild carnivores with the GnRH analogue deslorelin: preliminary observations. AB - The GnRH analogue deslorelin, in long-acting implants, was used in an attempt to temporarily control reproduction or aggression in wild carnivores in southern Africa and the USA. In the southern African study, 6 mg deslorelin was administered to cheetahs (eight females, four males), one female leopard and wild dogs (six females, one male) housed in groups, and 12 mg deslorelin was administered to two lionesses. None of the animals became pregnant after deslorelin administration apart from one wild dog that was mated at the initial treatment-induced oestrus. Two wild dogs and one lioness came into oestrus 12 and 18 months after deslorelin administration, respectively, thus demonstrating that the anti-fertility effects of deslorelin are reversible. Two lionesses and four cheetahs underwent oestrus without allowing mating 2-14 days after treatment. Simultaneous administration of progestins to three bitches and one lioness did not suppress oestrus. Male cheetahs had no spermatozoa on day 82 after treatment and did not impregnate two untreated females. Of three untreated female wild dogs housed with treated males, only the first female to enter oestrus (21 days after deslorelin administration) became pregnant. One month after treatment, plasma testosterone concentrations of male dogs were at basal values. In the USA study, three male sea otters that had been treated with 6 mg deslorelin ceased antagonistic behaviour and blood testosterone concentrations and size of the testes were still sharply reduced 24 months after treatment. Male red (n = 7) and grey (n = 5) wolves received 6 mg deslorelin in December 1998 but no effects on seasonal spermatogenesis and behaviour were observed. In a black-footed cat, sperm production, libido and aggressiveness decreased in response to treatment with 3 mg deslorelin and penile spines were not observed within 3 months after treatment, but were observed again 4-6 months later. Treatment of female red (n = 5) and grey (n = 5) wolves with deslorelin in December 1999 triggered preseason oestrus and mating, which were followed by one abortion and one successful pregnancy. Contraception was achieved in female Fennec foxes (n = 7) and two lionesses, which was observed in the foxes by an absence of increases in faecal progesterone concentrations. In two male bush dogs, administration of 3 mg deslorelin once or twice was insufficient to suppress reproductive function or behaviour. PMID- 11787163 TI - Potential for cloning dogs. AB - The aim of this study was to determine whether nuclear transplantation could be used to clone a dog using donor nucleus cells collected from an adult female. Fibroblasts obtained from skin biopsies were fused with enucleated bovine or canine oocytes. The resulting cloned embryos were cultured in vitro to monitor embryonic development. A proportion of the resulting embryos was transferred into surrogate bitches for development to term. When canine oocytes were used as recipient ova for canine fibroblasts, 23% of the resulting embryos cleaved at least once after culture in vitro. Five cloned embryos were transferred into three synchronized recipient bitches, but no pregnancies resulted. When bovine oocytes were used as recipinets for canine fibroblasts, 38% cleaved to the two- to four-cell stage and 43% cleaved to the eight- to 16-cell stage. Forty-seven of these embryos were transferred into four recipient females, resulting in a single conceptus that ceased development at about day 20 of gestation. The desire for cloned dogs is considerable and will undoubtedly incite the development of successful methods for cloning companion animals. However, significant investment into additional research is required, especially in the areas of in vitro maturation of oocytes and control of the oestrous cycle of bitches. PMID- 11787164 TI - Linkage of reproductive sciences: from 'quick fix' to 'integrated' conservation. AB - Our laboratory has experienced four phases in understanding how the reproductive sciences contribute to genuine conservation of biodiversity. The first is the 'quick fix phase' in which the erroneous assumption is made that extant knowledge and techniques are readily adaptable to an unstudied wild animal to produce offspring rapidly. The second is the 'species-specificity phase' in which it is recognized that every species has evolved unique reproductive mechanisms that must be mastered before propagation can be enhanced. The third is the 'applicability phase' in which one grasps that all the new knowledge and technology are of minimal relevance without the cooperation of wildlife managers. The final phase is 'integration', the realization that reproduction is only one component in an abundantly complex conservation puzzle that requires interweaving many scientific disciplines with elaborate biopolitical, economic and habitat variables. These phases are illustrated using 20 years of experience with wildlife species, including the cheetah, black-footed ferret and giant panda. We conclude that the foremost value of the reproductive sciences for conserving endangered species is the discipline's powerful laboratory tools for understanding species-specific reproductive mechanisms. Such scholarly information, when applied holistically, can be used to improve management by natural or, occasionally, assisted breeding. Genuine conservation is achieved only when the reproductive knowledge and technologies are integrated into multidisciplinary programmes that preserve species integrity ex situ and preferably in situ. PMID- 11787165 TI - Ovarian function and FSH receptor characteristics during canine anoestrus. AB - Ovaries of bitches are relatively inactive during anoestrus despite apparently adequate circulating FSH concentrations. Alternative FSH receptor (FSH-R) transcripts in bitches might hinder the follicular response to gonadotrophins, which may account for anoestrus. The expression of the full length FSH-R and novel isoforms in bitches was examined using in situ hybridization and RT-PCR analysis. Various PCR primers to the FSH-R were used and its expression was assessed in ovarian tissue at different stages of the oestrous cycle. RT-PCR amplification of the extracellular domain (exon 1-10) was generally successful, indicating that cFSH-R expression (> 90%) occurs throughout the oestrous cycle. Two FSH-R isoforms were sequenced, but there were no clear differences in the pattern of expression between anoestrus and other stages of the oestrous cycle, except that isoform expression was less frequent (30% occurrence) in prepubertal bitches. Data from in situ hybridization showed clear expression of the FSH-R in secondary and antral follicles, and corpora lutea. It was concluded that there is no evidence of a change in the expression of the FSH-R specific to anoestrus. PMID- 11787166 TI - Intratubal transplantation of early canine embryos. AB - It has been reported previously that intrauterine transplantation of canine embryos is possible. In this study, the possibility of intratubal transplantation of early canine embryos was investigated. Beagles at ovulation +/- 1 day estimated from peripheral blood progesterone concentrations were used as embryo donors and recipients. The Beagles (n = 13) were mated 1-4 days after ovulation and embryos were collected 1-3 days after mating (3-7 days after ovulation) by tubal flushing or salpingectomy. Embryos were transplanted using a glass tube or catheter into the upper or lower uterine tubes at 1.5 and 5.0 cm from the fimbriae tubae, respectively. The mean embryo yield from three bitches from which embryos were collected by tubal flushing was 28.2%. Embryos collected from ten bitches by salpingectomy were at the syngamy to eight-cell stages of development, and the mean yield was 95%. Embryos (1-7 per bitch) were transplanted into the upper uterine tube of seven recipient bitches and to the lower uterine tube of eight recipient bitches. It was found that no bitches in which embryos were transplanted into the upper uterine tubes became pregnant, whereas four bitches (50%) in which embryos were transplanted into the lower uterine tubes became pregnant (P < 0.05, chi-squared test). The success of embryo transfer was not affected by differences in embryo stage or day of ovulation. In conclusion, it is possible to impregnate bitches by transplanting early canine embryos into the lower uterine tubes. PMID- 11787167 TI - Determination of the role of cervical closure in fertility regulation after mating or artificial insemination in beagle bitches. AB - In the present study, the pregnancy rate after one insemination with fresh semen performed at the optimum period of fertilization (control) was compared with the pregnancy rate after insemination by either vaginal deposition of semen or transcervical uterine insemination at 24, 48 or 72 h after closure of the cervix (n = 5 bitches per time period and group). In the group of bitches inseminated into the uterus, 2 ml of a fresh pool of semen from four male dogs was deposited transcervically or by laparoscopy into the uterus, whereas in the vaginally inseminated animals, 2 ml fresh semen was extended with 4 ml prostatic fluid. The study was performed over 5 years; some bitches were used twice during two consecutive oestrous cycles. Closure of the cervix was determined once a day by retrograde vaginogram using a radiopaque contrast dye. Closure of the cervix occurred 6.9 +/- 1.1 days (mean +/- SD) after the LH peak and 1.5 +/- 0.9 days before the first day of cytological metoestrus. The hormone values at the time of closure were 81.2 +/- 12.3 nmol progesterone l-1 and 28.4 +/- 23.2 pmol oestradiol l-1; there were no differences between groups. Of the bitches inseminated before closure of the cervix, five and four bitches became pregnant after uterine and vaginal insemination, respectively. Of the bitches inseminated into the vagina 24, 48 or 72 h after cervical closure, none became pregnant, whereas three, three and one bitches became pregnant after insemination directly into the uterus at 24, 48 or 72 h after cervical closure, respectively. The mean litter size was 3.9 +/- 1.4 pups among all pregnant animals and there were no significant differences between groups. The results of the present study indicate that mature canine oocytes may remain fertile for > 200 h after ovulation, rather than for 48-60 h as was previously believed, and that cervical closure may be a limiting factor for reproductive success after natural mating. PMID- 11787168 TI - Establishment of assisted reproduction technologies in female and male African wild dogs (Lycaon pictus). AB - Transrectal ultrasonography, electroejaculation and cryopreservation of spermatozoa were applied to the African wild dog (Lycaon pictus) to establish non invasive protocols for assessing the reproductive health of one of the most endangered African canids. Transrectal ultrasonography was performed on immobilized male (n = 2) and female (n = 5) captive wild dogs. The testes and epididymides of the male dogs were imaged transcutaneously, followed by electrostimulation and cryopreservation of spermatozoa. The sonomorphology of the female and male urogenital tracts was characterized. In females, the vagina, cervix, non-pregnant uterus and ovary were imaged and the reproductive health of each female was evaluated. The sonographic assessment helped to identify one pyometra and extensive abdominal fat deposits in two other individuals in which pyometra had been suspected. Images of the adrenal glands showed differences in size among individuals of the same breeding group. Whether these differences were related to the dominance hierarchy remains to be determined. In males, visualization of the prostate gland, testis and epididymis indicated sexual maturity. Three ejaculatory fractions (1.0, 1.5 and 0.5 ml, with 50, 95 and 95% motility, respectively; 1.125 x 10(8) spermatozoa per ejaculate) were collected from one male. The motility of each of these fractions after thawing was 0, 30 and 40%, respectively. Electrostimulation of the second male, in which a cystic structure in a testis had been identified by sonography, resulted in an aspermic ejaculate (0.5 and 1.0 ml). These technologies provided basic data on reproduction in female and male African wild dogs and were an efficient way to evaluate reproductive health. PMID- 11787169 TI - Xenografting of canine ovarian tissue to ovariectomized severe combined immunodeficient (SCID) mice. AB - Xenografting of ovarian tissue salvaged from valuable dogs to an immunologically incompetent recipient is a possible mechanism to allow the ovarian tissue to be used for recovery of fertilizable oocytes. In this study, follicular development was assessed after xenotransplantation of fresh canine ovarian tissue into immunodeficient mice. Fresh prepubertal canine ovarian tissue was grafted beneath the kidney capsule of 7-week-old ovariectomized severe combined immunodeficient mice. At intervals after grafting, the recipient mice were killed, necropsied and the xenografts were recovered. The number and stage of development of follicles were assessed quantitatively by histological examination of serial sections of the xenografts. By day 56 after grafting, recruitment of primordial follicles had occurred but follicular development to the antral stage was not observed. The recipients showed persistent vaginal cornification and uterine dilation, which indicates that the grafts were producing hormones. However, these changes are not consistent with the oestrous cycle of either bitches or mice, indicating that inappropriate communication may occur between the recipient hypothalamic pituitary glands and the axis of the xenograft gonad. PMID- 11787170 TI - Effect of supplementation with the antioxidant astaxanthin on reproduction, pre weaning growth performance of kits and daily milk intake in mink. AB - The study comprised two parts. Firstly, the effects of dietary supplementation with an algal meal (Novasta) with a high astaxanthin content on ovulation rate (number of corpora lutea, implantation rate, number, mass and length of fetuses) of breeding female mink were evaluated. Secondly, reproductive outcome (number of live and stillborn kits), kit growth rate and milk intake were studied. Both studies were performed on standard brown female mink (n = 20; control (n = 10) and experimental (n = 10)) housed under conventional farm conditions. Experimental animals were supplied with 5.35 mg astaxanthin per day (0.25 g algal meal (Novasta)). The numbers of corpora lutea, implantation sites and fetuses appeared to be higher in the group that was given astaxanthin but the effect was not significant. The differences between treated and control mink were 1.4 (corpora lutea), 0.9 (implantation sites) and 1.2 (litter size). The percentage of stillborn kits was reduced by 6.3 (P < 0.005). The milk intake as measured by use of the isotopic water dilution technique was not affected by treatment group. Milk intake increased from about 19 g in week 1 of lactation to about 30 g per kit per day in week 4 of lactation. Kit weight gain was not affected by the experimental treatment. PMID- 11787171 TI - Induction of fertile oestrus in cats by administration of hCG and calcium naloxone. AB - The aim of this study was to evaluate the possibility of inducing fertile oestrus in queens by administering hCG in combination with Ca(2+)-naloxone. It is well established that an increase in endogenous opioids leads to a decrease in LH. The administration of naloxone, an opioid antagonist, inhibits endogenous opioidergic tone and induces the onset of pro-oestrus. The opioidergic block is related to the increase in binding of beta-endorphins to specific receptors, which determines calcium channel blockage. Pretreatment with hCG results in a rapid increase in the number of LH receptors and Ca(2+)-naloxone induces G protein activity. Twenty-one anoestrous queens were divided into four groups: (i) group 1, nine queens were treated with a single s.c. injection of hCG (1000 iu) and daily for 4 days with 0.1 ml kg-1 body weight i.m. of a solution containing 0.4 mg naloxone ml-1 dissolved in 20% calcium gluconate; (ii) group 2, four animals were treated with a single s.c. injection of hCG (1000 iu); (iii) group 3, four queens were treated with Ca(2+)-naloxone (0.1 ml body weight kg-1 i.m.) daily for 4 days; and (iv) group 4, four queens received no treatment (controls). Queens were monitored using vaginal cytology and blood progesterone concentrations, and pregnancy was detected using ultrasonography. In groups 2, 3 and 4 clinical signs of oestrus were not observed. In group 1, 88.8% of treated queens were mated (8 of 9) and ovulated on the basis of an increase in progesterone, and 75% (6 of 8) of these queens became pregnant. In conclusion, pretreatment with hCG increased the number of LH receptors and Ca(2+)-naloxone antagonized the hypothalamic GnRH opioid block thus inducing the pulsatility of LH leading to fertile oestrus in queens. PMID- 11787172 TI - Artificial insemination with frozen semen in dogs: a retrospective study. AB - In a retrospective study, from 1994 to 1998, of inseminations with frozen semen in dogs, a total of 312 bitches of 70 different breeds were inseminated with imported (n = 183) or domestic (n = 129) semen. The overall whelping rate was 70% and mean (+/- SEM) litter size was 5.3 +/- 0.2 pups. The whelping rate was higher after intrauterine insemination (71%; n = 305) than after intravaginal insemination (29%; n = 7; P < 0.05). Timing of insemination was crucial; timing classified as optimal resulted in a higher whelping rate and larger litter size (P < 0.05) than did timing classified as early, late or too late. In the too late category, none of the bitches (n = 5) whelped. For optimal timing, whelping rate and mean (+/- SEM) litter size were 76% (n = 252) and 5.6 +/- 0.2, for early 33% (n = 6) and 1.5 +/- 0.5, and for late 47% (n = 19) and 2.8 +/- 0.7. Two inseminations yielded a higher whelping rate (P < 0.05) and greater mean litter size (P < 0.05) than that of one insemination, 77% and 5.6 +/- 0.3, and 60% and 4.6 +/- 0.3, respectively. However, the results obtained after one insemination were poorer partly because of an over-representation of late insemination in this group. Semen classified as of poor quality (progressive motility < 50% or percentage of abnormal spermatozoa > 20%) gave a lower whelping rate (53%) than did semen of medium (progressive motility = 50%) or good quality (progressive motility > 50% and percentage of abnormal spermatozoa < 20%), which gave whelping rates of 76 and 74%, respectively (P < 0.05). The mean litter sizes were not significantly different. Eighty-two per cent of bitches (120 of 147) inseminated twice into the uterus at a time classified as optimal with frozen semen of good or medium quality whelped. The mean (+/- SEM) litter size was 5.6 +/- 0.3 pups in this group. These results show the potential of transcervical intrauterine insemination for routine artificial insemination in dogs. PMID- 11787173 TI - Intratubal insemination with fresh semen in cats. AB - There have been few reports of artificial insemination using fresh feline semen because of difficulties in collecting semen. It has been shown previously that the number of spermatozoa required for fertilization of cats by intravaginal insemination and unilateral intrauterine horn insemination are 8.0 x 10(7) and 8.0 x 10(6), respectively. There have been no reports of intratubal insemination of cats. Therefore, a study was designed to determine the number of spermatozoa necessary to fertilize cats by intratubal insemination with fresh semen. Four male and 25 mixed breed female cats were used. Semen was collected using an artificial vagina. Insemination was performed by laparotomy 15-30 h after administration of 100 iu hCG on day 2 or 3 of spontaneous oestrus. Cats in which ovulation had not occurred at insemination received an additional 100 iu hCG after surgery. In intratubal insemination, four groups consisting of three, seven, eight and seven cats received 5.0 x 10(3), 5.0 x 10(5), 2.0 x 10(6) and 4.0 x 10(6) viable spermatozoa, respectively, into both uterine tubes at approximately 2 cm from the fimbriae tubae. The volume inseminated was 10-20 microliters. The semen volume was adjusted with egg yolk-Tris-fructose citrate. As a result of artificial insemination, none of the cats that received 5.0 x 10(3) or 5.0 x 10(5) spermatozoa were fertilized. However, fertilization was successful in two of eight animals (25.0%) that received 2.0 x 10(6) spermatozoa and in three of seven animals (42.9%) that received 4.0 x 10(6) spermatozoa. The number of kits was 1-4 (mean +/- SE: 2.4 x 0.6). These results indicate that although large numbers of spermatozoa were inseminated into the uterine tubes, the conception rate was low. The low rate of conception may have been due to problems in inducing capacitation of spermatozoa in the uterine tubes. PMID- 11787174 TI - Association of endometrial degeneration in bitches with insufficient plasma progestagen concentrations. AB - The relationship between changes in plasma progesterone concentrations and endometrial degeneration in bitches was determined. Mature bitches (n = 14) were ovariectomized and treated with oestradiol benzoate for 11-12 days, followed by progestagen (2 mg megestrol acetate kg-1 body weight per day) for 35-37 days. Two bitches were necropsied at this stage (progestagen group). The other bitches were treated once a day for a further 3 weeks with 0.5 mg megestrol acetate kg-1 (decreased dose group; n = 3), 2 mg megestrol acetate kg-1 (standard dose group; n = 3), or 3 (1 week), 4 (1 week) and 5 (1 week) mg megestrol acetate kg-1 (increased dose group; n = 3), or received no treatment (withdrawal dose group; n = 3). A further five bitches with intact ovaries were examined during dioestrus (n = 4) and anoestrus (n = 1; 3 weeks after plasma progesterone concentration < 0.3 nmol l-1). Marked degeneration (> 80% cells) of the luminal epithelium was observed in the withdrawal dose and decreased dose groups, and in the intact bitches with plasma progesterone concentrations of 21, 36 and 39 nmol l-1. Medium (40-60% cells) degeneration was detected in the standard dose group and in the anoestrous bitch. However, a very small proportion (< 10%) of degenerated cells was found in the increased dose and progestagen groups, and no degeneration was detected in the dioestrous bitch with a plasma progesterone concentration of 90 nmol l-1. The numbers of endometrial leucocytes were low in all groups except for the withdrawal dose group and the anoestrous bitch. These results indicate that endometrial degeneration and exfoliation in bitches reflects a reduction or insufficiency of plasma progesterone concentrations. The mechanisms involved are unclear. PMID- 11787175 TI - Transcervical catheterization and cervical patency during the oestrous cycle in domestic cats. AB - The aims of the present study were to develop a device for vaginal and transcervical catheterization in domestic cats, and to study cervical patency during the various stages of the oestrous cycle. Seventeen queens submitted for routine spaying were included in the study. A vaginal catheter was designed from a urinary catheter for dogs, to fit into the ventral vaginal fornix, and a 3.5 French tomcat catheter was used as an inner transcervical catheter. Cervical patency was studied by infusing 0.5 ml Urografin into the cranial vagina and taking X-rays of the queens after 5 min. The Urografin did not enter the uterus, even in the oestrous queens. Transcervical catheterization was then attempted. The correct placement of the intrauterine catheter was confirmed by injecting green food colour mixed with penicillin G and observing the presence of stain in the uterine horns during surgery. Catheterization was successful in 13 of 17 queens: six of nine in interoestrus, three of three in oestrus, one of two in metoestrus and three of three in the postpartum period. Transcervical catheterization is a non-invasive technique that is likely to improve the success rate of assisted feline reproduction, and is potentially a useful non-surgical technique for diagnosis and therapy of uterine diseases. PMID- 11787176 TI - Vital and ultrastructural changes in dog spermatozoa during cyopreservation. AB - The exact nature of cryo-injury to dog semen and the stage of cryopreservation at which it occurs have not been evaluated fully and were investigated in the present study. Semen samples were examined immediately before and after addition of semen extender, cooling and freeze-thawing in a Tris-based medium. Vital and ultrastructural assessments were made immediately after each treatment and after incubation for 4 h at 39 degrees C after each treatment. Addition of semen extender produced no significant ultrastructural changes in spermatozoa; however, cooling resulted in an immediate increase in the number of acrosomal abnormalities and a subsequent decrease in sperm viability. Freeze-thawing caused both an immediate and a delayed decrease in sperm viability. This effect may have been an exacerbation of the effects of cooling as many acrosomal abnormalities were present or it may have been the result of initially unrecognized damage. Cooling and freezing of dog spermatozoa may have both immediate and delayed effects on the ultrastructure of spermatozoa. The immediate effects of cooling and freezing may either kill spermatozoa or render them incapable of fertilization by damaging the acrosome, whereas delayed effects may reduce sperm longevity by altering plasma membrane structure. PMID- 11787177 TI - Effects of three cryopreservation methods and two semen extenders on the quality of dog semen after thawing. AB - The aim of this study was to evaluate the influence of two diluents, one with and the other without Orvus ES paste, and three methods of cryopreservation on the quality of dog semen after thawing. The investigation was carried out on 126 ejaculates collected from 37 dogs. In Expt 1, sperm-rich fractions of ejaculates were frozen in 0.25 ml minitubes and pellets. In Expt 2, each sperm-rich fraction of ejaculate was divided and extended in two diluents, one with and the other without Orvus ES paste. Samples of semen were frozen in pellets and 0.5 ml French straws. Motility, percentage of spermatozoa with normal acrosomes and longevity of spermatozoa were significantly higher (P < 0.05) in semen samples frozen in pellets than in samples frozen in 0.25 ml minitubes. Aspartate aminotransferase activity in extracellular fluid was significantly (P < 0.05) lower in semen frozen in pellets. There were no significant differences in quality after thawing between semen samples frozen in pellets and 0.5 ml French straws. Longevity, unlike acrosome status and aspartate aminotransferase activity, was greater in samples extended in Tris-buffered diluent with addition of Orvus ES paste, regardless of the method of cryopreservation. PMID- 11787178 TI - Validation of flow cytometry for assessment of viability and acrosomal integrity of dog spermatozoa and for evaluation of different methods of cryopreservation. AB - The aims of the present study were: (i) to validate the accuracy of flow cytometry for assessment of viability and acrosomal status of canine spermatozoa; and (ii) to evaluate the cryopreservation protocols currently used for dog spermatozoa using flow cytometry. Data obtained by flow cytometry analysis of fresh dog spermatozoa stained with carboxyfluorescein diacetate (CFDA) and propidium iodide, or with fluorescein isothiocyanate (FITC)-conjugated Pisum sativum agglutinin (PSA) and propidium iodide, were compared with those obtained by microscopic evaluation. The results demonstrated that flow cytometry is a precise method for evaluating the viability and acrosomal status of fresh samples of dog semen. A new triple staining procedure, using carboxy-SNARF-1, propidium iodide and FITC-PSA, was developed and was an efficient method for evaluating the following aspects of cryopreservation protocols for dog spermatozoa: (i) addition of 0.5% (v/v) Equex STM paste to a Tris-egg yolk-based extender; (ii) dilution of the semen in one or two steps; (iii) freezing semen by placing 0.5 ml straws horizontally above liquid nitrogen in a styrofoam box or lowering them vertically into a liquid nitrogen tank; (iv) thawing semen at two different rates; (v) packaging semen at different sperm concentrations; and (vi) diluting semen at different rates after thawing. The highest sperm survival and longevity was obtained when Equex was present in the semen extender, the semen dilution was performed in two steps to obtain a concentration of 2.0 x 10(8) spermatozoa ml-1, the freezing was carried out using the styrofoam box, the straws were thawed at 70 degrees C for 8 s and the semen was diluted 1:4 after thawing. PMID- 11787179 TI - Effect of the inclusion of skimmed milk in freezing extenders on the viability of canine spermatozoa after thawing. AB - This study evaluated the effect of the inclusion of skimmed milk in freezing extenders on the motility, viability and acrosome morphology of canine spermatozoa after thawing. The Tris-glucose-citric acid buffer of a semen extender, which also included 20% egg yolk, 5% glycerol and 0.25% SDS, was replaced with 0, 50 or 100% skimmed milk. After thawing, the proportion of motile spermatozoa was not significantly different among semen extenders during incubation for 120 min at 37 degrees C. At 120 min after thawing sperm viability was significantly greater when an extender in which the buffer had been completely replaced by milk was used than in an extender in which the buffer had been partially replaced (P < 0.05). Acrosome morphology after thawing was similar for the three extenders tested. A considerable decrease in sperm motility and viability was observed during incubation, which may be due to concentrations of SDS that were not optimal. From these results it was concluded that the use of skimmed milk in extenders for freezing dog semen results in sperm motility and viability after thawing comparable to that obtained using a Tris-based buffer. PMID- 11787180 TI - Effect of prostatic fluid on motility, viability and acrosome integrity of chilled and frozen-thawed dog spermatozoa. AB - Sperm preservation has become a routine procedure in dog breeding. In this study, the influence of prostatic fluid on sperm characteristics after preservation (either chilling or freezing) was investigated. The sperm-rich fractions of 20 ejaculates from five dogs were either extended without centrifugation or centrifuged and resuspended either directly in extender or in prostatic fluid before dilution with extender. Aliquots were processed for storage at 4 degrees C for 6 h or for freezing. Storage at 4 degrees C did not affect sperm motility, viability or acrosome integrity, irrespective of the dilution treatment. However, sperm motility and viability decreased significantly after freezing and thawing, particularly in the samples with additional prostatic fluid. In contrast, the acrosome morphology of viable spermatozoa was not affected by either the dilution method or by chilling or freezing and thawing. It is concluded that addition of prostatic fluid during semen processing adversely affects the motility and viability of frozen-thawed spermatozoa. However, prostatic fluid does not appear to affect the motility and viability of chilled spermatozoa or to alter acrosome integrity in either system of preservation. PMID- 11787181 TI - In vitro maintenance, cooling and cryopreservation of red wolf (Canis rufus) spermatozoa. AB - A current priority for the preservation of the endangered red wolf (Canis rufus) is the development of a sperm-based genome resource bank. The aims of this study were to examine the effects of (i) holding temperature on the motility of spermatozoa over time, and (ii) cooling methods on the characteristics of spermatozoa after cooling and cryopreservation. Electroejaculates (n = 11; fresh) were evaluated for the percentage of motile spermatozoa, cell and acrosome morphology (Spermac (Meditech 1st Canada Inc, Montreal, Ontario) and fluorescein isothiocyanate-labelled Pisum sativum agglutinin lectin (PSA/FITC; Sigma Diagnostics, Oakville, Ontario) staining), and zona penetration. Semen samples were then divided into two equal samples and centrifuged to remove seminal plasma. One half of the ejaculate sample was re-suspended in sperm-Tyrode's albumin lactate pyruvate (TALP), divided into three aliquots and maintained either at room temperature (approximately 21-23 degrees C), 0 degree C or 37 degrees C. Sperm motility was examined at 0.5 and 1.0 h, and subsequently every hour for 10 h. Motility of spermatozoa decreased after 2 h, but was consistently greater at room temperature than at 37 degrees C or 0 degree C. The other half of the ejaculate sample was re-suspended in an egg yolk-based extender and divided into two aliquots. One aliquot was cooled in a refrigerator (5 degrees C) for 30 min, whereas the second aliquot was put into a beaker containing water at 37 degrees C, which was then placed into an ice bath until the sample reached 0 degree C (approximately 120 min). Spermatozoa were evaluated after cooling and after freezing and thawing treatments. No differences were observed between cooling treatments either after cooling or freezing and thawing. However, marked decreases in intact acrosomes, post-thaw motility and normal morphology of spermatozoa after treatment demonstrate that further investigations are necessary to improve cryopreservation methods in this species. PMID- 11787183 TI - A model for the study of cystic endometrial hyperplasia in bitches. AB - The aims of this study were: (i) to establish a reliable model for the study of cystic endometrial hyperplasia in ovariectomized bitches; and (ii) to assess the roles of oestrogen and progesterone in the pathogenesis of irritant-induced cystic endometrial hyperplasia. Greyhound bitches (n = 15) were ovariectomized and divided into five groups (n = 3 per group). After 3-4 weeks, oestradiol benzoate (0.6-4.8 micrograms kg-1, i.m.) was administered twice a day for 12 days to the bitches in group 1, followed by progesterone (0.2-1.8 mg kg-1, i.m.) twice a day for 30-33 days. These dosages were chosen to mimic the plasma hormone concentrations of a normal oestrous cycle. A silk suture was inserted by laparotomy into the left uterine horn 12 days into the simulated dioestrus (determined by vaginal cytology) and necropsy was performed after a further 12 days. For groups 2-5, the silk suture was positioned at ovariectomy. After a further 3-4 weeks, these bitches were treated with progesterone (group 2: 1.8 mg kg-1 i.m. twice a day), oestradiol benzoate (group 3: 0.6-4.8 micrograms kg-1 i.m. twice a day), oestradiol benzoate and progesterone together (group 4: previous dosages) or vehicle (group 5). Necropsies were performed after 12-13 days of treatment. Cystic endometrial hyperplasia was induced in the suture containing uterine horns of all bitches in groups 1 and 4, and in two bitches in group 2. Cystic endometrial hyperplasia did not develop in any control (no suture) uterine horns, or in either uterine horn of the bitches treated with either oestradiol only or vehicle. These results indicate that progesterone is necessary for the development of irritant-induced cystic endometrial hyperplasia and that oestradiol potentiates the effects of progesterone. The protocol used for bitches in group 1 would be a suitable model for further studies of the pathogenesis of cystic endometrial hyperplasia. PMID- 11787182 TI - Cystic endometrial hyperplasia/pyometra in dogs: a review of the causes and pathogenesis. AB - In this review the roles of endogenous and exogenous steroid hormones, steroid receptors, spontaneously occurring and experimentally induced genital tract infection, and endometrial trauma in the cause and pathogenesis of cystic endometrial hyperplasia/pyometra in bitches are considered. It is postulated that intrauterine bacteria, which ascend from the vagina during pro-oestrus and oestrus, induce the disease during metoestrus by acting on the progesterone primed endometrium directly via toxin production, or indirectly by the release of inflammatory mediators. The lesion can be produced by endometrial trauma in a sterile uterus without the systemic effects associated with the disease. There is no association with premature or increased progesterone concentrations at the time that the disease is normally diagnosed in mid- to late metoestrus; however, such aberrant endocrine changes cannot be excluded from involvement in the pathogenesis of this disease, as there are no data from bitches preceding the onset of clinical signs. Expression of oestrogen and progesterone receptors are modified by endogenous steroid hormones but there is no clear evidence that changes in these receptors are involved in the pathogenesis of the disease; receptor expression can be modified by exogenous hormones. PMID- 11787184 TI - Hysteroscopy in bitches. AB - The aim of this study was to determine whether the canine endometrium could be examined by hysteroscopy. Eight German shepherd bitches were used. Two bitches were in dioestrus, five were in anoestrus and one was about 8 weeks post partum. The uterus was exposed through a ventral celiotomy. A 3 mm straight laparoscope or a 4 mm laparoscope with a 30 degrees angle, and a catheter for inflation of the uterus were used. After hysteroscopy the bitches were spayed and the uterus of each bitch was examined macroscopically and histologically. Endometrium and uterotubal junctions were visible in all bitches. The cervix and caudal uterine body could not be visualized in three bitches as two bitches had uterine discharge and air escaped through the cervix in the other bitch. In the post partum bitch, dark-brown sites of implantation were observed. Four bitches (aged 9, 22, 25 and 31 months) had endometrial cysts (0.5-2.0 mm in diameter). Hysteroscopy caused petechiae and ecchymosis in the endometrium of four bitches. Traumatization of the endometrium affected only the epithelium and the most superficial part of the lamina propria. In conclusion, hysteroscopy appears to be a very sensitive tool for evaluation of the canine endometrium. Further research is necessary to determine the effects of hysteroscopy on subsequent fertility. PMID- 11787185 TI - Spermatogenesis and testicular tumours in ageing dogs. AB - The aims of this investigation were to quantify the changes in canine spermatogenesis that occur during ageing and to study the prevalence of testicular tumours and their effects on spermatogenesis in dogs. Testes from 74 dogs of various breeds without clinically detected testicular disease and from 28 dogs with clinically palpable tumours were examined. Testicular tumours were classified histologically according to the criteria of Nielsen and Kennedy (1990). Spermatogenesis was evaluated using a modified Johnsen score adapted for use in dogs. The diameter of the seminiferous tubules was measured in dogs without testicular disease to examine the possible effects of ageing. The different lifespans of small and large breeds were compensated for by expression as a percentage of the age at which dogs with various body weights are considered to be geriatric. Of the dogs without clinically detected disease, 21 of 74 had small testicular tumours. As in the 28 dogs with clinically detected tumours, multiple types of tumour and bilateral occurrence of tumours were common findings. The prevalence of tumours increased during ageing. Eighty-six per cent of the clinically detected tumours and 57% of the non-clinically detected tumours were found in geriatric dogs. The diameter of the seminiferous tubules did not change with age. Impairment of spermatogenesis was found only in dogs with bilateral tumours and in the affected testis of dogs with clinically detected tumours. In conclusion, it appears that spermatogenesis per se does not decrease during ageing in dogs. However, the occurrence of testicular tumours increases with age and this may affect spermatogenesis significantly. PMID- 11787186 TI - The phenomenon and significance of teratospermia in felids. AB - The common domestic cat is an important research model for endangered felids, as well as for studying genetic dysfunctions, infectious diseases and infertility in humans. Especially significant is the trait of teratospermia (ejaculation of < 40% morphologically normal spermatozoa) that commonly occurs in about 70% of the felid species or subspecies studied to date. Teratospermia, discovered more than two decades ago in the cheetah, is important: (i) for understanding the significance of sperm form and function; and (ii) because this condition is common in human males. It is apparent from IVF that deformed spermatozoa from teratospermic felids do not fertilize oocytes. However, the inability of spermatozoa from teratospermic males to bind, penetrate and decondense in the cytoplasm of the oocyte is not limited to malformed cells alone. Normal shaped spermatozoa from teratospermic males have reduced functional capacity. IVF results have consistently revealed a direct correlation between teratospermia and compromised sperm function across felid species and populations. The most significant differences between normospermic (> 60% normal spermatozoa per ejaculate) and teratospermic felids include: (i) the time required for sperm capacitation and the acrosome reaction to occur in vitro; (ii) culture media requirements for capacitation in vitro; (iii) phosphorylation patterns of tyrosine residues on sperm membrane proteins during capacitation; (iv) susceptibility to chilling-induced sperm membrane damage; (v) sensitivity to osmotic stress; (vi) stability of sperm DNA; (vii) sperm protamine composition; and (viii) fertilizing ability after intracytoplasmic sperm injection. In conclusion, (i) the felids (including wild species) are valuable for studying the functional significance of both pleiomorphic and normally formed spermatozoa from teratospermic donors, and (ii) the impact of teratospermia is expressed at both macrocellular and subcellular levels. PMID- 11787187 TI - A male to female sex-reversed dog with a reciprocal translocation. AB - A registered female Yorkshire terrier aged 3 years was diagnosed as intersex. Molecular and cytogenetic studies were carried out to determine whether chromosomal abnormalities were involved in the development of this condition. Analysis of the testicular tissue in the gonads and PCR amplification of three canine Y chromosome-specific DNA sequences from the genomic DNA of this animal indicated that the dog had a genetic complement with a Y chromosome. An analysis of > 100 banded metaphase chromosome spreads of this intersex dog showed uniformly a 78,XY chromosome complement and confirmed that the animal might be a male to female sex-reversed dog. However, two different types of X chromosome were observed. A whole chromosome painting probe was developed by microdissection of ten X chromosomes from the intersex dog and used for fluorescence in situ hybridization experiments on metaphase chromosome spreads from a normal male dog. Hybridization signals were detected on the X chromosome and on an autosome (not yet internationally standardized) indicating that a reciprocal translocation event had occurred. The karyotype of this mosaic sex-reversed dog was designated tentatively as 78,XY/78,XYrcp (X; autosome). This is believed to be the first report of a canine intersex dog showing male to female sex reversal. Further investigations should identify the autosome and the breaking points of the chromosomal rearrangement. These investigations potentially add to our knowledge of autosomal and X-linked loci involved in sexual differentiation of mammals. PMID- 11787188 TI - Population-based incidence of mammary tumours in some dog breeds. AB - Data from two population-based studies in four Norwegian counties were used to calculate the crude incidence of mammary tumours, and the age- and breed-specific incidence of mammary tumours in female dogs of three different breeds. The largest study comprised 14401 histologically verified tumour cases from four counties covered by the Norwegian Canine Cancer Register. The registry covers about 25% of the total Norwegian dog population. The second study was a census in Norway that was sent to all owners of the following breeds: boxers, bichon frise and Bernese mountain dogs, to estimate the age distribution of the female dog population at risk of developing mammary tumours. The crude incidence of malignant mammary tumours in female dogs of any breed was 53.3%. The highest relative risk ratio of mammary tumours was found in boxers, cocker spaniels, English springer spaniels and dachshunds. The mean age of histologically diagnosed mammary tumours was 7.9 years in boxers and 7.8 years in springer spaniels, compared with 8.8 years in all other breeds. In the four Norwegian counties from 1992 to 1997, the population-based incidence rates (for all ages) of malignant mammary tumours per 1000 female dogs per year were 35.47 in boxers, 3.87 in Bernese mountain dogs and 17.69 in bichon frise. Mammary cancer is the most common tumour in female dogs in Norway, and represents a population of almost entirely reproductively intact females. The age-specific incidence rates for mammary cancer vary considerably among the three breeds that were studied in detail. PMID- 11787189 TI - Oestrogen and progestagen treated ovariectomized bitches: a model for the study of uterine function. AB - The aim of this study was to validate a model in ovariectomized bitches for the study of uterine function. Mature bitches (n = 21) were ovariectomized and treated with oestradiol benzoate (0.6-4.8 micrograms kg-1, i.m. twice each day) and then with progestagen (megestrol acetate, 2 mg kg-1, p.o. once a day) and were necropsied at stages simulating pro-oestrus (n = 2), oestrus (n = 2) and dioestrus (n = 2). Other bitches received oestradiol benzoate and then megestrol acetate and were necropsied 3 weeks (midanoestrous group, n = 2) and 9 weeks (late anoestrous group, n = 2) after treatment. Untreated bitches (n = 1 per group) served as controls. The treatments induced oestrous behaviour, vulvar swelling, vulval discharge, vaginal smears, plasma oestradiol concentrations and uterine histology similar to that reported in intact bitches at each stage of the oestrous cycle. Marked endometrial degeneration and increased numbers of endometrial leucocytes were observed in the mid-anoestrous group. The endometrium was repaired in the late anoestrous group. A suture was placed in the lumen of the uterus of another six bitches at ovariectomy. Four of these bitches were treated with oestradiol benzoate and then megestrol acetate. Two bitches with a suture but not treated with hormones served as controls. In the hormone-treated bitches the suture resulted in cystic endometrial hyperplasia in two bitches and in cystic endometrial hyperplasia with pyometra in two bitches. The control bitches showed no cystic endometrial hyperplasia or pyometra. We have established in the ovariectomized bitch a model simulating the normal oestrous cycle that will facilitate studies of uterine function. This model will be used to study further the mechanisms of the endometrial degeneration and the pathogenesis of cystic endometrial hyperplasia. PMID- 11787190 TI - Dioestrous ovariectomy: a model to study the role of progesterone in the onset of canine pseudopregnancy. AB - It has been suggested that overt pseudopregnancy in bitches is caused by an increase in the concentration of serum prolactin as a result of an abrupt decrease in progesterone concentration in the late luteal phase. This hypothesis was tested by using ovariectomy at dioestrus as an experimental model. A total of 18 intact cross- and purebred bitches were used. Eleven animals were ovariectomized (day 0) between day 25 and day 40 of the oestrous cycle, and seven intact bitches were used as controls. Blood samples for determination of prolactin and progesterone concentrations were collected on days -1, 1, 2, 3 and 7 in the ovariectomized group, and on day 1 and day 7 in the control group. On day 7, the presence or absence of overt pseudopregnancy was recorded. The four ovariectomized bitches with a history of pseudopregnancy showed signs of overt pseudopregnancy (P < 0.01). On day 7, progesterone concentrations were significantly higher in the control than in the ovariectomized bitches (P < 0.01). The expected decrease in serum progesterone concentration after ovariectomy was similar in pseudopregnant bitches and non-pseudopregnant bitches. However, in pseudopregnant bitches, but not in non-pseudopregnant bitches, there was a marked increase (expressed as percentage change) in the concentration of prolactin between day -1 and day 7 (P < 0.01). It was concluded that the abrupt decrease in progesterone concentrations does not lead systematically to pseudopregnancy. Only in bitches predisposed to pseudopregnancy would an abrupt decrease in progesterone concentrations induce a substantial increase in prolactin concentrations, which in turn would trigger the typical signs of pseudopregnancy. PMID- 11787191 TI - Development of a technique for transcervical collection of uterine tissue in bitches. AB - Transcervical collection of endometrial tissue specimens is a valuable and well established tool for the diagnosis of reproductive disorders in cows, mares and women, but it is not used currently in bitches. Endometrial biopsy samples were collected by transcervical cannulation from the cranial uterine body at defined stages of the oestrous cycle using biopsy forceps. In study 1, the histology of 45 biopsy specimens taken from 23 Beagle bitches were compared with larger tissue samples collected post mortem. For further evaluation of representative biopsy specimens, the expression of oestrogen and progesterone receptors was determined. Only 31.1% of the biopsy samples taken from bitches could be evaluated and they showed stroma, capillaries, luminal epithelium, glandular ducts and apical glands; however, basal glands and myometrium were not observed. Biopsy findings were in agreement with the diagnosis of the uterine specimens concerning endometrial differentiation, inflammatory and degenerative lesions. The expression of oestrogen and progesterone receptors was slightly lower in the biopsy samples. In study 2, a total of 49 serial biopsy samples were taken from 12 Beagle bitches. In eight bitches, the manipulation resulted in a haemomucometra. Treatment with PGF2 alpha and antibiotics led to a clinical cure in five of these dogs, two of which were mated successfully during the next oestrus. Three animals had to undergo ovariohysterectomy. Owing to the small proportion of biopsy specimens that was suitable for analysis and the high risk of biopsy-related endometritis, transcervical biopsy collection cannot be recommended as a routine technique in bitches. PMID- 11787192 TI - Oestrogen concentrations in the faeces of bitches. AB - Few data are available concerning excretion of oestrogen from bitches. During anoestrus, oestrogen concentrations are low in the blood of bitches and, therefore, a sensitive method for measuring concentrations of these hormones by analysis of faeces was developed. Daily faecal samples from bitches (n = 25) of various breeds were analysed (collected for 20 days after the start of pro oestrous vulvar sanguinous discharge), as well as single samples from bitches in anoestrus (n = 30; samples from 16 of these bitches were also analysed during pro oestrus and oestrus) and ovariohysterectomized bitches (n = 18). Samples (0.5 g mixed with 0.5 ml water) were extracted and after the samples were cleaned the unconjugated oestrogen content was measured, using a group specific enzyme immunoassay. Oestrone and oestradiol were identified as the predominant immunoreactive oestrogens by HPLC. In samples collected on the first day of pro oestrous vulvar sanguinous discharge, oestrogen content was 9.3-231.1 nmol kg-1 faeces (median 45.5 nmol oestrogen kg-1 faeces). On day 8 of discharge, oestrogen content was 21.8-539.5 nmol kg-1 faeces (median 114.1 nmol oestrogen kg-1 faeces). Oestrogen content in bitches in anoestrus was 2.2-65.2 nmol kg-1 faeces (median 18.5 nmol oestrogen kg-1 faeces), whereas ovariohysterectomized bitches excreted lower amounts of oestrogens (range 0.7-18.1 nmol kg-1; median 4.4 nmol kg-1). The differences between oestrogen content in ovariohysterectomized bitches and bitches during anoestrus and oestrus were significant (P < 0.001). It is concluded that the method developed in the present study is suitable for monitoring the low production of oestrogens during anoestrus. PMID- 11787193 TI - Understanding the basic reproductive biology of wild felids by monitoring of faecal steroids. AB - The ability to track gonadal activity is essential for understanding the fundamentals of reproduction. Faecal steroid metabolite monitoring is a well established tool for evaluating reproductive processes in diverse mammalian species, including felids. Domestic cats were used as a model and injection of radiolabelled oestradiol, progesterone, testosterone and cortisol revealed that > 85% of metabolites were excreted in faeces with a time lag of 12-24 h. Steroids were extracted by boiling faecal material (wet or dry) in 90% aqueous ethanol followed by immunoassay with group-specific antibodies that crossreact with excreted metabolites. This approach was used to illustrate the diversity of oestrous cycle characteristics, gonadal responses to photoperiod and ovulatory sensitivity within the felid taxon. Longitudinal analyses demonstrated that faecal oestradiol increases with observed oestrus, and that the duration of the oestrous cycle varies among felid species. Seasonality in gonadal activity was observed in some species (for example clouded leopard, Pallas' cat), whereas other species (for example margay, cheetah, oncilla) are cyclic all year round. Although cats are considered induced ovulators, non-mating and spontaneous ovulation occurred in some species (for example domestic cat, clouded leopard, lion, leopard, margay) with varying frequency. There was also evidence that suppressed ovarian activity and oestrus occurred in group-housed cats (for example cheetahs). As assisted reproductive techniques, such as artificial insemination, are becoming increasingly important for managing zoo species, steroid metabolite monitoring has been especially useful for examining the efficacy of associated hormonal therapies. Exogenous gonadotrophins used to induce ovulation often caused ovarian hyperstimulation, which resulted in a maternal endocrine environment that differed from that of naturally mated cats. Finally, there is evidence that the adrenal status of animals managed under different husbandry conditions can be assessed non-invasively, thereby enhancing our understanding of how social and environmental factors affect animal well being and reproductive fitness. In summary, understanding the basic endocrinology of endangered felids generates knowledge that can be used to improve management strategies. Because of its enormous utility and non-invasive nature, faecal hormone monitoring is one of the most powerful tools available in zoo research today. PMID- 11787194 TI - Determination of concentrations of sex steroids in blood plasma and semen of male dogs treated with delmadinone acetate or finasteride. AB - The concentrations of testosterone, 5 alpha-dihydrotestosterone, oestradiol and oestrone were determined in peripheral blood plasma and semen of male dogs. In an experimental study, three Beagles were treated once with delmadinone acetate (1 mg kg-1 body weight, i.m.) and three were submitted to oral applications of finasteride (1 mg kg-1 body weight) once a day for 3 weeks. In a clinical study, 51 dogs of different breeds were divided into four groups according to the total number of spermatozoa in ejaculates (normospermia, slight oligozoospermia, severe oligozoospermia and azoospermia). The testosterone concentrations were significantly lower in sperm-rich ejaculate fractions and prostatic secretions compared with blood plasma (P < 0.05). The lowest concentration of testosterone was found in prostatic fluid. Concentrations of 5 alpha-dihydrotestosterone were similar in blood plasma and sperm-rich fractions, and significantly lower in prostatic secretions (P < 0.05). The concentrations of oestradiol and oestrone did not differ between blood plasma and either ejaculate fraction. Significantly higher 5 alpha-dihydrotestosterone concentrations and significantly lower concentrations of oestradiol and oestrone were found in prostatic secretions from azoospermic ejaculates compared with prostatic secretions of normospermic and oligozoospermic ejaculates. Delmadinone acetate and finasteride caused reversible suppression of the secretory activity of the prostate gland. The application of delmadinone acetate led to a temporary alteration of maturation of epididymal spermatozoa. PMID- 11787195 TI - Taurine and hypotaurine in spermatozoa and epididymal fluid of cats. AB - Taurine and hypotaurine have been found in spermatozoa and seminal plasma of numerous species and are known to have beneficial effects on sperm characteristics in mammals. Taurine is considered an essential dietary constituent in cats. Dietary deficiency has been associated with a range of serious clinical disorders. Quantification of taurine and hypotaurine in the genital tracts of male cats has not been reported. In this study, the concentrations of taurine and its precursors were measured in serum, spermatozoa, epididymal fluid and seminal plasma from cats. The concentrations of taurine measured in serum samples confirmed that the cats were not deficient in taurine. Significant amounts of taurine and hypotaurine were found in spermatozoa, seminal plasma and epididymal flushing fluid. Hypotaurine was not detected in serum samples. These results indicate that hypotaurine may be synthesized in cat testes or epididymides. Cysteamine was not detected in any of the samples. PMID- 11787196 TI - Links between nutrition and the reproductive axis in a seasonal breeder, the mink (Mustela vison). AB - This paper reviews some important links between nutrition and reproduction in a seasonal breeder, the mink (Mustela vison). The energetic costs of reproduction in mink are partly covered by mobilization of body fat reserves. A reduced food supply before the breeding season is detrimental to reproductive performance, and release of LH and ovulation may not occur in animals in extremely poor body condition. Nutritional flushing comprising a 2 week period of slightly restricted feeding, followed by ad libitum feeding for 4-5 days before the start of the mating season can influence reproductive performance positively. Reproductive endocrinology, ovulation and implantation rate, and early embryo development are affected by the modification of important metabolic signals including insulin, insulin-like growth factor I (IGF-I) and the thyroid hormones. PMID- 11787197 TI - [Hyperparathyroidism in clinical practice. Personal experience]. AB - The period of six years is discussed by the authors during which 39 patients were confirmed having primary or secondary hyperparathyroidism. All of them finally underwent the surgical procedure. The possibility of immunoreactive PTH measurement has been highly appreciated. Despite that key position of the experienced surgeon remains of the utmost importance. PMID- 11787198 TI - [Is the lingula suitable for evaluation of pulmonary biopsy? Results of pulmonary biopsies in patients during a 5-year period]. AB - Pulmonary biopsy is commonly performed for the diagnosis of interstitial pulmonary disease. The lingula has technical advantages on account of which it is frequently used. The quality of this tissue is however discutable. The authors submit a retrospective five-year group of 80 patients operated at the Surgical Clinic of the Faculty Hospital Plzen 53 times videothoracoscopically (66.2%) and 27 times by limited thoracotomy (33.8%). Both methods are in the authors opinion sufficiently effective to obtain bioptic material. The guide for localization of the biopsy is computed tomography. Only once from a total of 38 samples (2.6%) collected from the lingula an unequivocal diagnosis was not established. The authors assume therefore that pulmonary biopsy collected from the lingula is still justified. PMID- 11787199 TI - [The popliteal artery entrapment syndrome--personal experience]. AB - OBJECTIVE: In a retrospective study we analyze 5 patients with popliteal artery entrapment syndrome who were treated since 1999 to 2000 in our department. METHODS AND RESULTS: 5 patients were found to have popliteal vascular entrapment during a two-year period. From the total number of 5 patients, we performed surgery in 3 patients (5 operations). One patient rejected proposed surgical therapy, in another case the morphological lesion of the popliteal artery was not suitable for revascularisation. 3 patients underwent interposition of the diseased popliteal artery using a venous graft from a dorsal approach. Twice the decompression (myotomy) of the medial head of gastrocnemius muscle was sufficient. The study group is included in our follow up programme (median follow up 12.8 months, range from 3 to 24 months), primary and long term patency has been 100%. RESULTS: On the basis of our experience, we advice total replacement of the diseased popliteal artery. A dorsal approach (Hamming's "S" shaped incision) with interposition of the popliteal artery with autogenous venous graft, end to end anastomosis on both sides, seems to be the optimal solution. In case, the arterial wall is not irreversibly changed, surgical decompression (myotomy) is sufficient to prevent the development of symptomatic disease, also using the dorsal approach. PMID- 11787200 TI - [Subcutaneous emphysema caused by postoperative vomiting]. AB - The authors present 3 cases of subcutaneous emphysema after postoperative vomiting treated during a 4-year period. All patients were female, they underwent positioning during general anaesthesia--rotation on their abdomen and they vomited postoperatively with subsequent development of subcutaneous emphysema. The course was benign in all cases after conservative treatment. The authors discuss the possible etiology, diagnosis and treatment. PMID- 11787201 TI - [Acute hemorrhage in Crohn's disease]. AB - The authors present a case of profuse haemorrhage into the lower part of the digestive tract in a 17-year-old patient where Crohn's disease of the terminal ileum and right colon up to the hepatal flexure was diagnosed by sonographic examination. The haemorrhage occurred after preparation for coloscopic examination with Fortrans only 2 months after the onset of the first symptoms of the disease. Because of developing signs of haemorrhagic shock emergency surgery was necessary. Resection of the terminal ileum and dextrolateral hemicolectomy was performed and during operation coloscopy to eliminate further sources of haemorrhage. The patient recovered p.p.i. and was discharged on the 10th day after surgery. The authors discuss diagnostic and therapeutic pitfalls of this rare complication of Crohn's disease and compare their findings with data from the literature. PMID- 11787202 TI - [Colostomy and ileostomy and their complications]. AB - Establishment of an artificial intestinal outlet is even nowadays associated with a more than 50% postoperative morbidity. More frequent surgical complications are described in colostomies, patients with ileostomies are threatened more by a metabolic breakdown due to fluid loss via the stoma. This complication threatens patients with ileostomy not only in the early postoperative period but may represent also a long-term problem in particular in risk patients. The authors evaluated complications associated with establishment of an artificial outlet of the gut in 88 patients operated in 1999-2000. Complications were more frequently recorded in patients with colostomy, i.e. in 9.7%. In 80.8% patients with ileostomies fluid losses via the stoma exceeding 1000 ml/24 hours were observed. Early and systematic replacement of water and minerals prevented the development of serious metabolic and circulatory disorders. The authors consider a priority solution in particular in temporary derivation of the intestinal passage establishment of an ileostomy despite the risk of metabolic complications. PMID- 11787203 TI - [Post-resection dumping syndrome (case report)]. AB - During the last twenty years a significant reduction of the number of gastric resections on account of peptic ulceration occurred due to better therapeutic possibilities in gastrodudodenal ulcers and due to changes in the epidemiology of gastric tumours. However, resections are made, frequently on account of complicated cases of unsuccessful treatment of ulcers in "treatment at any cost". This problem was frequently the subject of professional discussions. Therefore we consider it important to remind young colleagues of the omitted chapter of possible pathological conditions which develop after gastric resections. The latter include a group of vasomotor, gastrointestinal and humoral symptoms which develop as a result of the loss of reservoir function and the function of the closing mechanism of the pyloroantral part of the stomach after gastric resections in derivation surgery. In addition to data in the literature reporting that dumping syndrome is encountered only in 2-3% of any gastric operation the authors describe two of their own observations and the results of their surgical treatment. PMID- 11787204 TI - [The development of bariatric surgery and the role of the First Surgical Clinic of the General Medical School Hospital and the First Medical School of Charles University in Prague in this specialty]. AB - The authors discuss the development of bariatric surgery in Europe and the USA from its beginnings at the onset of the fifties. More detailed attention is paid in particular to the development of the method of gastric bandings and the role at the First Surgical Department in this field in "classical" as well as miniinvasive surgery. Results of gastric banding are summarized in 683 patients operated since 1983, in particular the numbers of early and late complications after laparotomies and laparoscopic operations, similarly as complications which are directly associated with gastric banding itself. In the conclusion it is stated that the First Surgical Department of the General Faculty Hospital and First Medical Faculty Charles University in Prague belong as regards their results in surgical treatment of obese subjects and the position in the field of bariatric surgery on an international scale to the foremost departments in this field worldwide. PMID- 11787205 TI - [Complications in treatment of a patient with total aganglionosis of the large intestine]. AB - The author presents a patient with an congenital malformation, megacolon congenitum, with total agangliosis of the large bowel. Total colectomy was performed preserving part of the rectum with subsequent Duhamel's operation. After four years, at the age of 5.5 years the postoperative course was complicated by an inflammation of the rectum with the subsequent development of multiple fistulae in the perianal, perineal, gluteal and labial area. The condition had a rapid septic course. The patient was subjected to repeated ileostomy. Under general antibiotic treatment and Sulfasalazine the patient's condition improved. PMID- 11787206 TI - [Local staging of rectal carcinoma--comparison of endorectal ultrasonography and CT]. AB - Correct staging of adenocarcinoma of the rectum is mandatory before any therapeutic choice is made. Important features are infiltration of the perirectal fatty tissue (T3 and T4) and the presence of locoregional lymphatic spread. Computed tomography with rectal air insufflation (CT) was compared with transrectal ultrasonography (TRUS) in 212 patients. Results of the preoperative examinations were compared with histological findings. The CT examination in evaluation of perirectal spread had an accuracy rate of 76%, sensitivity of 86% and specificity of 62%, the corresponding figures for TRUS were 83%, 91% and 66%. The accuracy, sensitivity and specificity of CT for nodal involvement were 51%, 57% and 50% and of TRUS 60%, 68% and 59%. These findings confirm that TRUS is more accurate than CT in local tumour staging (T) and in detecting nodal spread (A). PMID- 11787207 TI - [Metastatic choriocarcinoma as a cause of hemorrhage in the digestive tract and abdominal cavity]. AB - Authors present a case report of an young woman with metastatic choriocarcinoma. Clinical presentation of the disease was intracerebral bleeding concurring with intestinal bleeding and bleeding from ruptured spleen according to metastatic spread. Physicians firstly didn't think of choriocarcinoma because of small incidence of the disease and long period after the patient's latest pregnancy. At last the aggressive treatment was successful. Authors would like to bring out the reality that the surgeon could be the first who is faced with diagnosis and treatment of serious complications of choriocarcinoma. PMID- 11787208 TI - [Early breast carcinoma--diagnosis and therapy]. AB - The authors are presenting a review of the current state of diagnosis and surgical treatment of the early breast cancer, an algorithm of the diagnosis and the treatment. The authors are showing the impact of the breast preserving surgery and from their point of view present experience with 362 patients operated at the General Surgery Pardubice assembled in years 1998 and 1999. PMID- 11787209 TI - [Supracondylar fractures of the humerus and disorders of circulation]. AB - Supracondylar fractures (SF) of the humerus are the third most common type of fractures in childhood. The highest rate of pulselessness fracture of the distal humerus is the extension-type. The aim of our treatment is to minimize potential complications. Our management of pulselessness supracondylar fracture is more aggressive compared with other dpts. 223 (100%) patients with SF were treated at the dpt. of Paediatric Surgery, University Children's Hospital in Bratislava, in the 5-year period of (1995-1999). 11 (4.93%) patients remained pulseless after reposition of bone fragments. These patients underwent surgical revision of the brachial artery. Spasms of the brachial artery (BA) occurred in six patients, a lesion of BA in three patients and thrombosis of BA in two patients. We performed revision of the brachial artery by a Fogarthy catheter in six patients--in four cases with thrombectomy. In two cases we released the vessel from bone fragments. In two patients was replaced the injured segment of the brachial artery by a venous allotransplant. Peroperative angiography was performed in six patients. We reoperated three patients with early postoperative complications. We did not record any case of Volkmann's contracture. PMID- 11787210 TI - [Will medicine find its identity in the new century? Part I: Medicine--health- disease]. AB - Identity of medicine is determined by its constitutional and essential characteristics that identify it with itself and deliminate medicine from other fields of science. Its basic principle is a new philosophical view on the health and disease and their mutual relationship. To the four traditional models of health the fifth one is added--the continual bio-psycho-social concept: The complex health-disease is a dynamic entity formed by a continuous array of mutually interconnected stays of variously large and measurable health capacity, sensitively responding to stimuli of the social environment. Opinions on the disease causes are expressed in the bio-ecologic model, based on the view of multicausality and multilevel effects of various different factors at all structural levels, among which the principal role has the socio-economic macrosphere. PMID- 11787211 TI - [Toxic megacolon]. AB - Toxic megacolon belongs to the severe acute complications of inflammatory bowel diseases. The frequency is 1.6-21.4% among patients with ulcerative colitis and 0.3-2% in those with Crohn's disease. The main characteristics of toxic megacolon are toxemia, sepsis and distension of the colon due to the diminished muscular tone, loss of motor activity and increased amount of colonic gas. Sepsis and/or perforation of the large bowel can complicate this situation. The most important diagnostic procedure is the abdominal X-ray. Should the diameter of colonic distension exceed 60 mm, the diagnosis of toxic megacolon has been confirmed. Conservative treatment of toxic megacolon consists of water and electrolyte replacement, total parenteral nutrition, administration of corticosteroids and broad-spectrum antibiotics and repeat patient's prone positioning. If medical therapy is not successful during the first 72 hours, surgical intervention is indicated. The most common procedure is subtotal colonic resection with creation of an ileostomy. Patients with toxic megacolon should be managed at specialised centers, where cooperation of experienced gastroenterologists, surgeons and intensive care experts is possible. PMID- 11787212 TI - [Different trends in cardiovascular mortality in the Czech and Slovak Republics after the partition of Czechoslovakia in 1993]. AB - BACKGROUND: Development of health status aimed on cardiovascular mortality of male and female population in Czech and Slovak republics after the partition of the common state between years 1993 and 1999 is compared. METHODS AND RESULTS: Within the followed seven years the mean life expectancy at birth in Czech Republic (CR) linearly increased by 2.6 years in males (p = 0.00001) and 1.9 years in females (p = 0.0001). In Slovak Republic (SR) life expectancy increased in males only by 0.5 years and by 0.3 years in females (not significant). The main cause of such state is related to differences in cardiovascular mortality; standardised early cardiovascular mortality in age interval 0 do 64 years significantly lowered in males and females in both republics, the decrease being significantly higher in CR (p < 0.001). At present, the early cardiovascular mortality of males and females is over 30% higher than in CR. Similar development had also the early mortality rate among males and females on the ischaemic hearth disease (p < 0.05) and on cerebrovascular disease. Differences between SR and CR in mortality rate of the ischaemic heart disease (not the prevalence of the cerebrovascular disease) carry on also in 1999. Significant different was the development of cardiovascular mortality in the population over 64 years: In CR the decrease was continuous and highly significant (p = 0.000), meanwhile in SR the trend has the opposite direction. At present in SR is the cardiovascular mortality of males and females over 64 years higher than that in 1993. To the difference in the mean life expectancy of males in SR contribute also the higher infant mortality, the early cancer mortality, mortality to external causes, and the diseases of the respiratory and alimentary system. CONCLUSIONS: Causes of the different development in SR and CR are not well recognised. They may include the lower level of education, worse composition of the diet, higher consummation of distillates and tobacco, and somehow lower level of health care in SR. Also the higher proportion of the Romany population in SR may be significant. PMID- 11787213 TI - [Characteristics of pregnancy, labor and low birth weight neonates. Part II]. AB - BACKGROUND: The study wants to find out the characteristics of pregnancies, deliveries and newborns with low birth weight (LBW) compared to the newborns with birth weight of 2500 g and more, in respect with the specific situation of the twins. METHODS AND RESULTS: The records from antenatal clinics and maternity hospitals about 5500 children born within strictly given time limit of 16 months during the years 1991-1992 to mothers with permanent habitation in Brno were evaluated. Children and their families are participating on still running prospective longitudinal study ELSPAC aimed to finding the determinants of the healthy development. The low birth weight occurred in 5.42% of children. There were altogether 48 pairs of twins, the low birth weight occurred in 52.6% of them. Compared to mothers who delivered the children with birth weight of 2500 g and more, the mothers of children with low birth weight entered the prenatal care later, with less consultations, had more complications both during their pregnancies and the deliveries and their children showed more often different kinds of neonatal morbidity. Mothers of the twins were cooperating with antenatal clinics better than other mothers of children with low birth weight. On the other hand, they were suffering from anaemia and hypertension more often than mothers of single children. Comparison of the somatic and functional signs has shown that the twins were less handicapped than the whole set of newborns with low birth weight. The twins with low birth weight formed 16.7% of the set. CONCLUSIONS: The study of the Brno newborn population shows the quantitative differences in the risks, which have influenced the courses and the results of the pregnancies ending by deliveries of children with low birth weight. Results are compared to those whith deliveries of children the birth weight of 2500 g and more. PMID- 11787214 TI - [Meningeal carcinomatosis as the first manifestation of gastric adenocarcinoma]. AB - Gastric adenocarcinoma is rarely observed in patients under the age of 40. Meningeal carcinomatosis as a first manifestation of disease is absolutely unique. If meningeal involvement occurs it is usually secondary event in previously diagnosed tumor. The prognosis is very unfavorable associated with short term survival. In the treatment of this disease there night be used either chemotherapy administered via lumbar injection or radiotherapy or combination of both. This case study is one of very few cases reported in literature when meningeal carcinomatosis was a first sign of advanced gastric adenocarcinoma. 39 years old woman was admitted to our hospital with severe headache, diplopia and vomiting. Meningeal carcinomatosis with gastric primary was diagnosed. She was treated with combination of cytosine arabinosid (Cytosar), methotrexate (Methotrexat), hydrocortisone (Hydrocortisone) administered via intrathecal lumbar injection and whole brain radiation. As a main complication she experienced disseminated intravascular coagulopathy. The improvement of patient's condition following the initial treatment had a very limited duration and the patient died of bilateral pneumonia and cerebral edema 44th day after the admission. PMID- 11787215 TI - [Gene therapy of hemophilia--the next disappointment?]. AB - Since the very beginning the evident target of gene therapy were monogenic disease, though the number of applicated protocols in the treatment by oncologic processes has become much higher now. Several clinical studies, using viral vectors or direct transfer of plasmids containing sequences of human factor VIII, from which the central part (domain B) had been deleted gave satisfactory results concerning the transfer effectivity. On the other hand the amount of factor VIII produced in recipients was decreasing and was no more detectable after one year after administration of transfected fibroblasts. PMID- 11787216 TI - [Could Hammurabi have had a cataract operation?]. PMID- 11787217 TI - [Emergencies during the three months after leaving the maternity hospital]. AB - Parents are aware that young age is a risk factor and are more likely to take an infant to the emergency room than an older child with similar symptoms. It is essential that the physician rapidly responds to the concerns of such parents. It is not possible to exhaustively address in a few pages all of the potential emergency conditions that may arise with infants younger than three months. We therefore focus our discussion to the most frequently occurring emergency conditions. In particular, we emphasize the serious nature of such conditions as fever, apparent life threatening, hyperbilirubinemia, weight loss, and excessive crying. PMID- 11787218 TI - [Pediatric surgical emergencies]. AB - A quarter of pediatric surgical emergencies are non trauma and are for most of them limping child, acute abdominal pain, and acute scrotum. All of the child's lower limb pathology can be described as a limp, and the same is true for abdominal pain and acute scrotum. We will describe the important inquiring and clinical tools as well as a few simple paraclinics that allow to recognize the few cases requiring emergency care. PMID- 11787219 TI - [Respiratory emergencies in infants]. AB - Respiratory distress in childhood is a frequent cause of admission to the emergency department. The initial management requires a rapid clinical evaluation in order to initiate appropriate interventions, which will improve respiratory status, and avoid cardiac arrest and hypoxic encephalopathy. There are many possible etiologies but in the vast majority of cases the following conditions are observed: nasal obstruction before 3 months and laryngitis after 6 months. Moreover, during winter acute viral bronchiolitis is the most common disease of the respiratory tract during the first year of life, and occurs in annual epidemics. The diagnostic of an inhaled foreign body must always be suspected. Prevention is based upon information given to families, as well as the medical community, which often minimises the seriousness of inhalation hazards. PMID- 11787220 TI - [Acute gastroenteritis and dehydration in infants]. AB - Gastroenteritis continue to be a major cause of mortality and morbidity worldwide. The main objectives in the approach to a child with acute gastroenteritis are to assess the degree of dehydration and provide fluid and electrolyte replacement. The general agreement among paediatric gastroenterologists is to consider that the optimal management of acute gastroenteritis in mild to moderately dehydrated children in Europe should consist of the following practical guidelines: use of oral fast rehydration solution (ORS) to correct estimated dehydration over 3-4 hours using an hypo osmolar solution; continuation of breast feeding throughout; early refeeding i.e. resumption of normal diet (without restriction of lactose intake) after 4 hours rehydration in most children, while maintaining supplementing fluids with ORS in order to prevent further dehydration; no unnecessary medication. PMID- 11787221 TI - [Bacterial meningitis and purpura fulminans in the child]. AB - Antimicrobial therapy must start promptly. Antimicrobial regimen is adapted to the data of epidemiological trends. Bacterial meningitis of children are a matter of therapeutical urgency. Diagnosis must be easily considered according to the clinical analysis. Fulminant meningococcal sepsis is the most alarming clinical presentation of the meningococcal diseases. PMID- 11787222 TI - [Neurologic emergencies in the child]. AB - Febrile seizures are the main causes of seizures in infants and children. They are caused by the fever without infectious of nervous central system. The diagnosis of acute encephalitis should be suspected in febrile children whose level of consciousness is progressively altered and who present with partial seizures and motor deficit. The two most classical etiologies of ataxias are cerebellar involvement or deep sensibility disorder. Acute drug poisoning and viral infections are the most common causes. Intracranial hypertension is due to an abnormal increase in cerebrospinal fluid pression. Acute form may be a life threatening or complication of chronic intracranial hypertension. Despite its high frequency, benign form should be remain a diagnosis of exclusion. PMID- 11787223 TI - [Acute intoxication in the child]. AB - Acute intoxications of children remain too frequents, despite of an open decrease of mortality and a regression of morbidity in less than 20 years. Medicaments are in the majority, but their gravity concern the house caustic, industrial products (White spirit, oil, antifreeze), fertilizers and herbicides, the carbon monoxide intoxication. Many parents are careless or make several behaviour's mistakes, which mislead youngsters of less 4 or 5 years. Quick help to regional CAP, or 15 by failure, good medical advice, early arrival to emergency unit, or the displacement, very exceptional, of SMUR's team, at last, now well systematize therapeutics indications have allowed to realize very great progress since the eighties. PMID- 11787225 TI - [The fourth mission...]. PMID- 11787224 TI - [Drugs for pediatric emergencies]. AB - Drugs for pediatric emergencies are useful for respiratory (croup, asthma), cardiologic (hypertensive crisis, acute congestive heart failure, arrhythmias, hypoxic spells), neurologic (seizures), metabolic (dehydration, hypoglycaemia), infectious (meningococcemia) or allergic (anaphylaxis) distresses. Pain management is always important whether to relieve or to prevent the discomfort which would happen during diagnosis or therapeutic procedures. PMID- 11787226 TI - [Thrombocytopenia]. PMID- 11787227 TI - [Measuring the population's state of health]. PMID- 11787228 TI - [Aortic insufficiency. Etiology, physiopathology, diagnosis, development]. PMID- 11787229 TI - [Followup of normal infants, children and adolescents. Screening for vision disorders]. PMID- 11787230 TI - [Erythema. Diagnostic approach]. PMID- 11787231 TI - [Ankylosing spondylitis]. PMID- 11787232 TI - [Modern therapy of hematologic malignancies]. AB - Remarkable progress has been done during the last three decades in the therapy of hematological malignancies. It is now possible to cure significant number of patients by chemotherapy, radiotherapy, and stem cell transplantation. However, there is still a large group of patients and situations where our approaches are failing. It is evident that in some circumstance chemotherapy and radiotherapy get close to their limits. A short insight into the group of novel therapeutic methods is given in this review. Such promising methods of treatment include the new chemotherapeutic drugs, new molecules that specifically act on the level molecular mechanisms (STI 571, ATRA, arsenic trioxide, etc.), immunotherapy (monoclonal antibodies, vaccination strategy, exploration of dendritic cells etc.), gene therapy and innovations in stem cell transplantation (graft versus leukemia/lymphoma effect). The future treatment will include combination of standard or intensified chemo/radiotherapy and the new methods, which allow better control of the disease. PMID- 11787233 TI - [Benign hyperplasia of the prostate--a known and unknown disease]. AB - Authors give an overview of the current approaches to diagnostics and therapy of the benign hyperplasia of the prostate (BPH). The up-to-date diagnostic possibilities are cited in the relation to our health care system and the procedures of conservative and surgical treatment of BPH are outlined. In epidemiology and diagnostics of BPH, one has always to consider the possibility of prostate cancer (PC), which may have similar symptoms, particularly in initial stages. If prostate cancer were found, it could be successfully cured at this stage only. Drug therapy or BPH enables in most cases at least temporarily to resign on surgical treatment. Patients treated with alphablockers regularly speak about an improved quality of life regarding previous micturition troubles. To diagnose BPH, the complex urological examination is needed, including some laboratory tests (prostate specific antigen PSA, uroflowmetry UFM). The article is supplemented with a graph of latest available figures referring to the number of TURPs performed annually and a table showing the list of methods for the minimal invasive surgical treatment of BPH. PMID- 11787234 TI - [High-dose busulfan--monitoring plasma levels and dosage adjustments in adults]. AB - Bone marrow and peripheral blood stem cell transplantations, despite their curative potential, still carry significant risks for patients. Toxicity of high dose chemotherapy is one of the leading causes of peritransplant mortality. Busulfan is a frequently used chemotherapeutic agent in conditioning regimens prior to transplantations. The choice of the optimal busulfan dose and prediction of its clinical effect may be very difficult. Absorption of busulfan from gastrointestinal tract and its metabolism can vary considerably. Several studies published recently showed that the busulfan plasma concentrations correlate better with the clinical effect and extramedullary toxicity caused by this drug than with the actual dose administered to the patient. Approximate target plasma concentrations of busulfan, which meet the optimal balance between the clinical effect and the risk of severe side effects of chemotherapy, were proposed. Almost twenty chromatographic methods were published, which make the quantitative measurement of busulfan possible. The maintenance of certain busulfan plasma concentration during its whole administration with the help of the repeated adjustments of its dosage can reduce the toxicity caused by this agent and improve the results of bone marrow or peripheral blood stem cell transplantations. This method is easily applicable, has low financial and personal demands, and technical appliances, which it requires are usually accessible in most transplant center laboratories. PMID- 11787235 TI - [What is the fate of our smallest patients? Follow-up of children with a birth weight less than 1000 g]. AB - BACKGROUND: The neurodevelopmental status of infants of birth weight lower than 1000 g born between 1994-1998 at the age of 2 years. METHODS AND RESULTS: Infants of birth weight lower than 1000 g born between January 1994 and December 1998 and discharged from NICU of the Charles University Hospital in Pilsen were followed up longitudinally. Physical, somatometric, neurologic, ophthalmologic, psychologic (Bayley II Mental Developmental Index) and foniatric assessment was made at 24 months of the corrected age. 143 premature newborns (under 1000 g) were born during this period, 91 survived (36.3%) and were discharged home. 76 children (84%) were evaluated at the age of 2 years. Children were divided into 3 groups: normal neurodevelopmental outcome, mild and major impairment. 80% of children were normal., 9% with mild a 11% with major impairment in the whole group. According to the birth weight the impairment distribution was as follows. Birth weight 500-749 g: normal developmental outcome--71%, mild--18% and major impairment 11%. Birth weight 750-999 g: 83% normal outcome, 4% mild and 13% major impairment. CONCLUSIONS: We determined relatively high proportion (80%) of normal neurodevelopmental status among originally extremely premature children. Major developmental impairment (mainly cerebral palsy) was found in 11% of children. There was no significant outcome differences between two birth weight cohorts. PMID- 11787236 TI - [Metabolic complications and neurologic manifestations of vitamin B12 deficiency in children of vegetarian mothers]. AB - BACKGROUND: Serious hematological, metabolic and neurological complications owing to the nutritional deficiency of vitamin B12 may occur in infants of mothers on a strict vegetarian diet. METHODS AND RESULTS: The mother of the first child was a strict vegetarian. She had an elevated urinary methylmalonic acid level and a low concentration of serum vitamin B12. Her 13-month-old daughter was exclusively breast-fed until the age of 9 month and then she was fed only vegetables. Physical examination revealed psychomotoric retardation, apathy, muscular hypotonia, abnormal movements and failure to thrive. Laboratory analysis showed a megaloblastic anaemia, a low level of vitamin B12 and methylmalonic aciduria. MRI of the brain revealed diffuse frontotemporoparietal atrophy and retardation of myelination. After treatment with vitamin B12 supplements, abnormal movements disappeared and development improved, but a mild generalised hypotonia continued. A cranial MRI 9 months after treatment still showed signs of retardation of myelination. The second patient, an 8 month-old male, son of a strict vegetarian mother too, was referred for investigation of psychomotoric retardation, hypotonia, dyskinesia, failure to thrive and microcephaly. He was breast-fed and from 6 month of age he had also received fruit juices. Laboratory analysis revealed megaloblastic anaemia, high methylmalonic aciduria and homocystinuria. The patient's and his mother's serum level of vitamin B12 were low. After treatment with vitamin B12 supplements, biochemical and metabolic markers of disease were normal but there continued a generalised hypotonia, microcephaly and language delay. CONCLUSION: Our observations emphasize the health complications of nutritional cobalamine deficiency and a requirement of clinical, biochemical and metabolic monitoring in infants within strict vegetarian families. PMID- 11787237 TI - Implementing an evidence-based acute gastroenteritis guideline at a children's hospital. AB - BACKGROUND: Guidelines for preventing and treating acute gastroenteritis (AGE) have generally not been incorporated into medical practice. An evidence-based clinical practice guideline was adapted from national guidelines to meet the practice styles characterizing care in southwestern Ohio and implemented at the Children's Hospital Medical Center (Cincinnati). Its efficacy was assessed in terms of emergency department (ED) encounters and admissions, mean and total hospital costs, and mean length of hospitalization. METHODS: Comparisons were made between patients seen during peak gastroenteritis months (December-May) before (fiscal year [FYs] 1994-1997) and after (FYs 1998 and 1999) guideline implementation. Data were extracted from hospital charts, clinical databases, and billing records. RESULTS: Following implementation, mean yearly ED encounters for AGE decreased 22% and mean yearly admissions decreased 33%. The percentage of admitted children with minor illness decreased (p = 0.002). Mean length of stay decreased 21% for children with minor illness (p = 0.0001) and 5% for others. Hydration status was noted in only 15% of ED charts examined but increased to 63% in FY 1998 and 86% in FY 1999 (p < 0.001). The proportion of admitted patients who advanced to a regular diet by discharge increased from 4.9% (FY 1997) to 23% (FY 1998) and 76% (FY 1999; p < 0.0001). Total inpatient days/year decreased by 43%. Mean hospital costs did not change significantly. DISCUSSION: Following implementation, fewer patients with AGE were seen in the ED and fewer were admitted to the hospital for care. Hospital stays were shorter, and children were more likely to resume their diets before discharge. PMID- 11787238 TI - Using a unit assessment tool to optimize patient flow and staffing in a community hospital. AB - BACKGROUND: Hospital environments are too often characterized by delays for patients receiving diagnostic testing and prolonged waiting times to complete needed therapy. Frequently there is confusion in scheduling, related at least in part to the complex interplay of clinical acuity and highly individualized care. Luther Midelfort recently began to change the process of patient flow to improve access to care, optimize outcomes by enabling timely intervention, and decrease the wasting of resources. UNIT ASSESSMENT TOOL: The hospital developed a unit assessment tool based on the traffic light concept, which consisted of an assessment of current capacity and a graded, color-coded "workload tolerance" for each hospital unit. Each unit can instantly update its own status and query those of other work environments in the hospital. EXPERIENCE WITH THE UNIT ASSESSMENT TOOL: For most of the January-July 2001 period, there was generally a progressive decrease in the percentage of time that the units were coded as red (unit closed to new admissions), with concurrent increases in the percentage of time that the units were coded as green (unit open). Use of the tool appears to have contributed to a dramatic increase in staff satisfaction. SUMMARY AND CONCLUSIONS: The key to regulating patient flow has been to adopt a nursing initiated capping trust policy whereby nurses are given the authority to limit new admissions. Initiatives are now under way to provide different units with novel models of resource sharing, ranging from flexible housekeeping to "flying nurse squads" to assist units that have become red. PMID- 11787239 TI - A quality improvement curriculum for medical students. AB - BACKGROUND: Despite frequent recommendations that quality improvement (QI) be incorporated into medical education, reports of this activity are few. A pilot project to develop and implement a curriculum on QI into a family medicine clerkship was conducted in the 1999-2000 academic year. INTERVENTION: A five-part curriculum was developed and implemented on successive weeks of a family medicine clerkship. The curriculum involved students working alone and in small groups. After an orientation to QI principles, students performed a series of chart audits of diabetes care. They then met with QI coordinators from a local health system to review their results. Improvement recommendations were developed and presented to the clinic director. Evaluation included completion of the module, assessment of student knowledge and opinion, and interviews with the QI coordinators. EVALUATION: Two clinic sites and 30 third-year medical (M3) students participated. Each student conducted at least two chart audits, met with the QI coordinators, and developed at least one improvement recommendation. The QI coordinators felt that students were interested in the subject but needed more training in QI principles and more faculty development. Students assessed the curriculum as being moderately effective and useful. DISCUSSION: A curriculum in QI that involved active learning strategies was successfully implemented during a family medicine clerkship. Students viewed the curriculum as being appropriate to their learning. Future efforts should include more work on faculty development and role modeling of QI activity. PMID- 11787240 TI - Taking the national guideline for care of acute myocardial infarction to the bedside: developing the guideline applied in practice (GAP) initiative in Southeast Michigan. AB - BACKGROUND: The Guideline Applied in Practice (GAP) program was developed in 2000 to improve the quality of care by improving adherence to clinical practice guidelines. For the first GAP project, the American College of Cardiology (ACC) partnered with the Southeast Michigan Quality Forum Cardiovascular Subgroup and the Michigan Peer Review Organization (MPRO) to develop interventions that might facilitate the use of the ACC/AHA Acute Myocardial Infarction (AMI) guideline in the practice setting. Ten Michigan hospitals participated in implementing the project, which began in March 2000. DESIGNING THE PROJECT: The project developed a multifaceted intervention aimed at key players in the care delivery triangle: the physician, nurse, and patient. Intervention components included a project kick-off presentation and dinner, creation and implementation of a customized tool kit, identification and assignment of local nurse and physician opinion leaders, grand rounds site visits, and measurement before and after the intervention. IMPLEMENTING THE PROJECT: The GAP project experience suggests that hospitals are enthusiastic about partnering with ACC to improve quality of care; partners can work together to develop a program for guideline implementation; rapid-cycle implementation is possible with the GAP model; guidelines and quality indicators for AMI are well accepted; and hospitals can adapt the national guideline for care into usable tools focused on physicians, nurses, and patients. DISCUSSION: Important structure and process changes--both of which are required for successful QI efforts--have been demonstrated in this project. Ultimately, the failure or success of this initiative will depend on an indication that the demonstrated improvement in the quality indicators is sustained over time. PMID- 11787241 TI - Passing the flag--from Christchurch to San Diego! PMID- 11787242 TI - Monitoring of occupational exposure in manufacturing of stainless steel constructions. Part I: Chromium, iron, manganese, molybdenum, nickel and vanadium in the workplace air of stainless steel welders. AB - Exposure to workplace airborne pollutants was examined in a group of 20 workers dealing mainly with welding, polishing, drilling and assembling of stainless steel constructions. Airborne particulate matter (APM) collected using both personal and stationary samplers was analyzed by instrumental neutron activation analysis (INAA). Quality assurance procedures of both sampling and analytical stages are described. Of the elements determined, results are presented for chromium, iron, manganese, molybdenum, nickel and vanadium. The median values of element concentrations exceeded the maximum admissible limits for workplace pollutants only for chromium, while for nickel the limit was exceeded in several individual cases. Sampling of hair, nails, blood, urine and saliva to be used for biological monitoring of the exposed and control groups is also described. PMID- 11787244 TI - Drug Information System in the Czech Republic. AB - The Drug Information System (DIS) enables to monitor: incidence (the numbers of newly registered problem drug users); prevalence (the numbers of existing problem users visiting treatment/contact centres in a certain time period or as of a certain date); types of used drugs, manner of their application, frequency of use, their availability, purity; health (but also social consequences) of drug use (hepatitis, HIV; social and economic consequences); demographic profile of affected persons (age, sex, employment, education, etc.); time trends showing potential changes of the above specified indicators, including changes in the geographic distribution. Hygienic Service was mandated to create and operate the DIS in the Czech Republic. The system has been in operation since 1 January 1995 and it is based on the monitoring of basic health indicators. PMID- 11787243 TI - Trichomonas vaginalis in vaginal smears of women using intrauterine contraceptive device. AB - To detect the association between the use of an intrauterine contraceptive device (IUCD) and the presence of Trichomonas vaginalis (Tv), vaginal smears of 1110 women were examined cytologically. Among 45 IUCD users, 10 women were positive for Tv (22.22%). Forty six of 1065 non-users were also positive for Tv (4.32%). There was a significant correlation between the use of IUCD and the presence of Tv (p < 0.05). The data also indicated that the prolonged use (> or = 3 years) of copper-IUCD may promote the growth of Tv in the vaginal mucosa. This result will be a clue to diagnose asymptomatic patients for Tv. PMID- 11787245 TI - Musculoskeletal disorders among construction apprentices in Hungary. AB - The purpose of this study was to determine the prevalence of occupationally related musculoskeletal disorder (MSD) symptoms and carpal tunnel syndrome (CTS) among construction apprentices in Hungary. Symptoms of occupational MSDs and the job factors contributing to the symptoms were determined through an administered symptom and job factors survey. The prevalence of CTS was based on a case definition that included hand symptoms and nerve conduction studies of the median nerve across the carpal tunnel. The participation rate was 96% among the 201 eligible construction apprentices. More than 50% of the apprentices reported occupationally related musculoskeletal symptoms in the previous 12 months. Job tasks that required awkward postures and working in a static position were the two factors that contributed most to MSD symptoms. No cases of CTS were found in this sample of apprentices. Although disorders of the musculoskeletal system are more prevalent among experienced construction workers, this study indicated that symptoms of MSDs are present among young construction workers. Assessing the magnitude and nature of occupational related MSDs is the first step in promoting a healthier, safer, and more efficient workforce. PMID- 11787246 TI - Spontaneous missed abortion caused by Ascaris lumbricoides. AB - In this report, a case of spontaneous missed abortion caused by Ascaris lumbricoides is presented and data from the literature are reviewed, A 26-year old pregnant woman was presented with abnormal genital bleeding, abdominal pain. PMID- 11787247 TI - Retrospective study of concentration levels of Pb, Cd, Cu and Se in serum of the Czech population in time period 1970-1999. AB - The retrospective study evolution of trends in concentrations of Cd, Pb, Cu and Se in the population of the Czech Republic over 30 years period could be useful in design of regulations concerning health protection, prevention of diseases caused by deficiency of trace elements and have considerable economic importance. Concentrations of the named elements in the serum were determined by means of atomic absorption spectrometry (AAS) after mineralisation in a microwave digestion system. The 1433 samples of serum (730 males and 703 females, average age 48.7 and 49.1 years respectively) from a time period 1970-1995 were obtained from the Serum bank of National Institute of Public Health and volunteers (1999). Serum samples from the years 1970, 1975, 1980, 1985, 1990, 1995 and 1999 were examined. The accuracy of the results was checked by means of the Control material Seronorm Whole Blood 404,107 and Seronorm Serum 704,121, Nycomed. The concentration of Cd had a decreasing trend for the years 1975-1999 (0.82 microgram Cd.l-1 vs 0.47 microgram Cd.l-1). The levels of Pb are falling in the interval 1970-1980 (15.6 micrograms Pb.l-1 vs. 6.6 micrograms Pb.l-1). In year 1985 concentration of Pb increased (10.7 micrograms Pb.l-1) but subsequently decreased again (1995--6.4 micrograms Pb.l-1). In year 1999, it was 8.9 micrograms.l-1. The concentration of Cu decreased in period 1970-1990 (1525 micrograms Cu.l-1 vs. 990 micrograms Cu.l-1). From 1990 to 1999 the levels of Cu had an increasing tendency (1999--1060 micrograms Cu.l-1). Levels of Se in the interval 1970-1985 were surprisingly equal (58.1 micrograms Se.l(-1)-54.4 micrograms Se.l-1). However in the interval 1986-1990 the level of Se sharp declined (38.3 micrograms Se.l-1). Since 1990 levels of Se in serum increased again, up to 67.1 micrograms Se.l-1 in 1999. Statistically significant differences between men and women were found only in Cu and Pb concentrations. Concentrations of under study elements corresponded to the published values concerning unexposed population. PMID- 11787248 TI - Determination of arsenic in water--quality assurance and calculation of metrological characteristics. AB - Arsenic is a toxic element, acting as a nerve poison and proven carcinogen. Its main source for humans is drinking water where the most important are arsenic (V) compounds. With respect to the Slovak standard, in force since 1998, the maximum tolerable value is defined as the important characteristic of drinking water. If the value 0.01 mg.l-1 of arsenic is exceeded, water is not drinkable. The mentioned standard defines criteria for precision of the arsenic determination and the corresponding limit of detection--being 10% of the maximum tolerable value. Arsenic content in the drinking water samples was measured by the AAS method. Internal Quality Control for analysis by the ETA AAS method was based on the harmonised guidelines recommended by IUPAC, ISO and AOAC. The following metrological characteristics were calculated: precision, accuracy, and the yield of the arsenic standard addition to the studied sample--matrix spike and analytical spike. In addition to it, a thorough study of the limit of detection, LOD, and the limit of quantification (determination), LOQ, was performed. The LOD and LOQ values were calculated in the traditional way as well as by the ULA technique, newly recommended by IUPAC. In the latter case, the calculated LOD value was close to the demanded 10% limit of the maximum tolerable value, which is 1 microgram.l-1 As. The repeatability and reproducibility, found at two concentration levels 56.02 +/- 0.73 micrograms.l-1 and 6.0 +/- 0.9 microgramsl-1, were 3.2% and 3.9%, respectively, and 7.1% and 9.8%, respectively. Trueness of the applied AAS method was proven satisfactory on the reference material SRM 1643 Trace Elements in Water. PMID- 11787249 TI - Vascular and nerve disorders at exposure to hand-held vibrating tools related to ISO 5349. AB - The authors present the results of the investigation of peripheral nerves of the hand in a group of 30 glass cutters, 21 metal grinders, 10 blacksmiths and 24 workers who worked with nailers. The measurements of vibrotactile sensitivity were carried out by Vibrometry System Bruel & Kjaer Type 9627. The vibrotactile perception thresholds (VPT) were measured in frequency range from 8 to 500 Hz. The same investigations were carried out in 103 healthy subjects with no previous work-exposure to vibration or shocks. Further electromyographic examination was carried out in all members of exposed groups. The results of measurements VPT have proved reliability and high sensitivity of this method for the early detection of light disorders of peripheral nerves of the hand due to vibration. All the workers also passed investigation of vascular system of fingers. Simultaneously the measurement of vibration and shocks of single types of hand held tools used by workers was done. The results of measurement have been worked up according to ISO 5349 (1) that enables to determine the beginning of the incidence of disorders of the hands and arms on the base of measured values of vibration and shocks. The results of the vascular system investigation have been compared with the results of the assessment of exposure according to ISO 5349. The conformity has been proved in the case of hand-transmitted vibrations not in the case of shocks. PMID- 11787250 TI - Monitoring of national drug policies--regional comparison between Bulgaria, Romania, Macedonia, Bosnia Herzegovina. AB - After the profound economic and political changes most of the East European countries started market-oriented reforms. During the last 10 years rapid development of the private pharmaceutical sector and a slow privatisation process was observed. The balance between the private and public sector became very important for achieving NDP goals. The goal of this study is to evaluate the availability and development of the NDP structures in East European countries- Bulgaria (BG). Romania (Rom), Macedonia (Mac), Bosnia Herzegovina (BiH). For the assessment of the availability of NDP structures a questionnaire focused on seven main NDP components was used. These components are: legislation and regulations; essential drug selection and drug registration; drug allocation in the health budget/public sector financing policy; public sector procurement procedures; public sector distribution and logistics; price policy; information and continuing education on drug use. According to the survey the most developed NDP structures are drug legislation and regulations (incl. quality control), drug registration and drug distribution. We can assume that the people have access to different drugs of appropriate quality and in time. The systems for public drug financing, procurement and price policy are under developing or not efficient enough. The financial availability of drugs is difficult. There is a lack of objective drug information and postgraduate education is not oriented on the ED. It means that there is no guarantee for rational drug prescription and usage of drugs on the markets. PMID- 11787251 TI - Opportunities for integration into ordinary school of students with emotional and behavioral disorders and students with chronic cardiovascular diseases (representative study for Republic of Bulgaria). AB - This article reviews the results of a representative study on the opportunities for integration into mainstream school of students with emotional and behavioral disorders and students with chronic cardiovascular disease. The aim of the study is to clarify some important personal characteristics as well as some factors, related to the school and family environment of students with EBD and those with chronic CVD in order to assess their capacities for integration. Altogether 192 students aged 8-15 years with psychic disorders and 337 aged 15-18 years with cardiovascular diseases were followed for two and four years respectively. Results show that students with EBD are with limited cognitive capacities, emotionally unstable, introverts, with high level of psychotisicm and higher level of personal anxiety compared to their healthy coavals. Students with EBD, studying with the healthy children, compared to their coevals with the same diagnoses, but studying separately in recovery school "pure model of special school" are with better short-term memory, lower level of situation anxiety, better mental work capacity and as whole more successfully socialized. In the end of the second year of investigation their psychic health improves as well. All this allow us to draw the conclusion that the integrated education of pupils with EBD has a better effect on the psychic health and improves as a whole their learning potentialities. Beside some significant differences between the students with CVD and the healthy referents, in terms of social and family status, school performance, school relationships, personal and cognitive characteristics, they could successfully be integrated into the public school in the presence of a well organized and individualized health, social and pedagogic support. PMID- 11787252 TI - Did the nutrition of Slovak medical students change? A comparison after 15 years. AB - OBJECTIVE: Authors aimed at positive and negative changes evaluation in nutrition and nutritional status of university-medical students comparing the situation in years 1984 and 1999. They were trying to determine, how was the nutrition of current medical students influenced by food consumption changes in the Slovak population and price liberalization of the food-stuffs as well. MATERIAL AND METHODS: Seven day reports from the year 1984 (199 students) and from the year 1999 (228 students) were processed using Food Research Institute, Food Composition Database and Programme. The quantity and quality of consumed food stuffs and beverages were evaluated as well as energy and biologic value of students nutrition. Nutritional status of students was assessed by BMI (body mass index--kg/m2). Men and women (years 1999 vs. 1984) were separately evaluated by standard statistical methods. RESULTS: Lower energy, fat, cholesterol, animal protein and salt intake were observed in students in the year 1999; on the contrary, carbohydrates, sucrose, fibre, magnesium, vitamins C and E intake increased in comparison with the year 1984. The differences were mostly significant in women. Big changes in food consumption (1999 vs. 1984) were observed. Current students eat less meat (less pork, beef, fish, but more poultry), eggs and potatoes and women also less milk and dairy products than in the year 1984. On the contrary, the consumption of vegetable, fruits, legumes and non-alcoholic beverages increased. Alcohol intake decreased significantly. Students eat the most on Sunday, the least on Friday; women eat more rationally. Nutritional status in man was not changed, the percentage of slim women increased (p < 0.05). CONCLUSION: The food of current students (1999) is more varied, with the balanced content of plant and animal sources and with lower energy density than in the year 1984. Negative consequences of price liberalization in medical student nutrition are lower in comparison with Slovak global nutritional trends and they reflect the higher health awareness, eventually better socio-economic family background. PMID- 11787254 TI - A proposal of action plan for pandemic influenza caused by a new virus variant- the National Pandemic Plan of the Czech Republic (NPP-CR). PMID- 11787253 TI - High prevalence of HIV risk-behavior and the identification of predictors for sharing injecting materials among young drug users in Prague, Czech Republic. AB - This study is one of the first studies in the Czech Republic evaluating the extent of the HIV epidemic among drug users. Interview data on demographics, drug use, sexual practices, and HIV knowledge and risk perception were obtained from study participants and a saliva sample was obtained for an HIV antibody test. Although the HIV infection rate is low (0.2%), the prevalence of high risk behaviors, such as sharing injecting equipment and unsafe sexual practices, indicate a potential for rapid HIV spread in this high risk population. Preventive measures need to be targeted toward drug users, especially those of younger age and women. PMID- 11787255 TI - Evaluation of the lame patient. AB - Competence in evaluating lameness is vital for the veterinary practitioner. This skill is becoming even more important with the increasing popularity of large breed dogs and the corresponding increase in the number of developmental orthopedic problems seen on a day-to-day basis. A proper physical examination of the lame patient is essential to the management of the case. This article reviews the initial evaluation of the lame veterinary patient without dwelling on the specific differential diagnoses and corresponding treatments. PMID- 11787257 TI - Hind limb lameness in the mature dog. AB - This article describes the differential diagnosis of hind limb lameness in adult dogs with common clinical presentations and diagnostic methods outlined. PMID- 11787256 TI - Hind limb lameness in the young patient. AB - Hind limb lameness is seen frequently in young dogs and may result from congenital abnormalities, traumatic injuries, or developmental diseases. An understanding of the patient's history, a good physical and radiographic evaluation, and sound knowledge of the common diseases affecting immature dogs permit early diagnosis and successful treatment in most cases. PMID- 11787258 TI - Feline lameness. AB - Feline lameness is an increasingly recognized clinical problem. Today's veterinary practitioner must be comfortable with his/her ability to diagnose the various conditions responsible for lameness in the cat and be able to discuss the significance of their findings with the client. Disease of the feline musculoskeletal system can be grouped into broad categories, including: trauma, arthritis, infectious causes, developmental disorders, neoplasia, and muscular problems. Specific diseases from each of these categories will be discussed, particularly those that differ in their presentation or clinical behavior from that same disease in the canine patient. PMID- 11787259 TI - Diagnostic imaging of lameness in small animals. AB - The demand for advanced diagnostic imaging procedures such as nuclear scintigraphy, ultrasonography, computed tomography, and magnetic resonance imaging has increased dramatically over the past 10 years. Veterinarians, seeking to improve their diagnostic capabilities and clients willing to pursue "best medicine" have driven this demand, resulting in installation of advanced imaging facilities at most academic and private referral practices. Knowledge of potential benefits of various modalities will allow the veterinarian to optimize his or her use of diagnostic imaging in his or her own practice or in a referral practice. PMID- 11787260 TI - Neurologic conditions causing lameness in companion animals. AB - Animals presented with non-weight-bearing lameness are a diagnostic challenge for the veterinarian. It is extremely important to distinguish between orthopedic and neurologic causes of lameness, because the diagnostic and therapeutic plans can be quite different. Myopathies can be confused with orthopedic disease because of gait abnormalities and associated muscle pain. Common myopathies seen in companion animal medicine include polymyositis, muscular dystrophy, endocrine and infectious myopathies, and myasthenia gravis. Lameness caused by disease of the nerve root or nerve is confused with orthopedic disease because of the disturbances of a nerve's sensory distribution (nerve-root signature) or disruption of the motor innervation. The diseases of the nerve root or nerve discussed are lateralized intervertebral disk disease, spinal cord neoplasia, malignant peripheral nerve sheath tumors, and traumatic neuropathies. The diagnosis of these diseases requires careful attention to the signalment, a complete history, and a thorough physical examination focusing on the neurologic and orthopedic components. Ancillary testing should be selected based on these results and a minimum database. Electrodiagnostic testing, radiography, and advanced imaging may help to localize the lesion more precisely and sometimes to confirm the diagnosis. Surgical exploration and histopathology often provide the definitive diagnosis. These cases of non-weight-bearing lameness are a diagnostic challenge, but when successful resolution can be reached, it is gratifying to the clinician, client, and patient. PMID- 11787261 TI - Ancillary diagnostic techniques for the lame patient. AB - The cause of lameness is usually identified through evaluation of signalment, history, and physical examination. Radiographic evaluation provides a definitive diagnosis in many cases; however, laboratory evaluation may prove useful in the characterization of certain conditions or in the prognostication of the condition. In some instances where the definitive diagnosis remains elusive, arthroscopic examination is a minimally invasive diagnostic tool that may be more affordable and available than computed tomography. This article reviews laboratory evaluation of the lame patient and arthroscopic evaluation of joint abnormalities. PMID- 11787262 TI - Kinetic and kinematic gait analysis in dogs. AB - Kinetic and kinematic gait analysis provides objective, quantifiable, and repeatable information on normal and abnormal gait in dogs. Data collection requires specialized equipment, and techniques must be carefully controlled to ensure that accurate measurements are obtained. Force-plate and kinematic analysis is currently used primarily as a research tool to study various gait abnormalities and objectively assess treatment efficacy. As future research identifies characteristic changes associated with specific types of lameness, the use of gait analysis to evaluate individual clinical patients with lameness should become more valuable. Specialized gait analysis techniques may eventually enable veterinarians to accurately diagnose subtle lameness, better evaluate dogs with resolving lameness, and accurately select the appropriate time to return an athletic dog to exercise after recovery from an injury. PMID- 11787263 TI - Overview of pain in the lame patient. AB - Pain is often the limiting factor associated with joint disease. Pain results from the stimulation of nociceptors by excessive mechanical stimulation, chemical stimulation associated with the inflammatory process, or a combination of both. Even though OA is considered to be a noninflammatory disease, the mild degree of inflammation frequently associated with this condition can result in peripheral sensitization. This results in increased spontaneous activity and decreased activation threshold of nociceptive fibers. Activity of the primary joint afferents also leads to changes within the dorsal spinal horn, resulting in central sensitization and changes in the neural structures of the dorsal horn that facilitate and amplify the nociceptive response. Changes in the periarticular tissues correspond to the neurobiologic changes, resulting in increased stimulation of nociceptors caused by mechanical and chemical alterations resulting from tissue damage. Similar pathophysiologic events occur regardless of whether the initiating event is an acute joint injury or a chronic condition such as OA. The combination of these events results in the complex dynamic of joint pain. Because of this complex interaction of the musculoskeletal and nervous systems, it is difficult to imagine a single treatment that is effective for the alleviation of pain, because that agent would require inhibition of a number of stimulatory pathways. Instead, restoration of mechanical integrity, relief of peripheral inflammation, and blockage of central neurotransmission are all likely to have a role in the relief of joint pain and resolution of lameness. PMID- 11787264 TI - Forelimb lameness in the young patient. AB - Forelimb lameness is a common problem in young dogs and can be caused by a wide variety of problems. Accurate and comprehensive diagnosis and treatment must be provided for these patients. Differential diagnoses for forelimb lameness in the young patient fall into the categories of congenital abnormalities; developmental disorders; trauma; and infectious, nutritional, metabolic, and neoplastic causes. The etiopathogeneses of many of these disorders are still unknown, and treatment options and prognoses vary tremendously. Until definitive causes are determined, it is the responsibility of veterinarians to address the factors that contribute to the development and progression of these disorders. These areas primarily involve weight and nutritional management as well as breeding programs. PMID- 11787265 TI - Forelimb lameness in the adult patient. AB - Lameness of the forelimb may be one of the more frustrating problems in small animal orthopedics. It is likely that numerous causes of forelimb lameness are not yet defined or well understood. The common and some less common causes of forelimb lameness are discussed as well as their means of diagnosis. The application of new diagnostic tools including arthroscopy and ultrasound are also discussed. PMID- 11787266 TI - [Parenchymal cerebral hemorrhage and hypertensive crisis. A clinical proposal]. AB - The clinical evolution of patients with cerebrovascular accident (CVA), is analyzed. It is demonstrated that all CVA, that in its beginning is accompanied by an hypertensive crisis, is hemorrhagic unless shown otherwise. PMID- 11787267 TI - Accidents among drillers in the Venezuelan oil industry in 1993. AB - In 1993 a total of 356 accidents with injuries occurred in workers of 26 companies of oil and gas extraction in the eastern coast of Maracaibo Lake in Venezuela. 288 of them worked in drilling tasks. With the purpose of analyzing the factors that are associated with the drilling activities, the data base of the Venezuela Institute of Social Security, was reviewed. Only the first two digits of the Standard Industrial Classification were used in this study. For preventive reasons this study focused on six variables: unsafe condition or mechanical cause, insecure action, external agent, type of the accident, part of the body injured and the nature of the injury. The following results were obtained: the frequency rate was 222.3 by 1,000, most of them were minor and were caused by not paying attention when walking on or around labor areas (37%), thus favoring being struck by lifting machines (14%); also 62% occurred in non classified conditions that injured the upper and lower extremities (48% and 24%) producing contusions and crushing (39%). In conclusion, most injuries occurring in the activity of oil and gas extraction are due to factors controllable with preventive strategies. PMID- 11787268 TI - In mice the efficiency of immunization with Venezuelan Equine Encephalomyelitis virus TC-83 is transiently increased by dehydroepiandrosterone. AB - To determine whether treatment with dehydroepiandrosterone (DHEA) improves the efficiency of immunization against the Venezuelan Equine Encephalomyelitis (VEE) virus, mice were vaccinated with the TC-83 VEE virus. DHEA (10 mg/kg) was administered in a single dose, 4 hours before vaccination. IgM antibody titers were determined at days 7, 14 and 21 post-immunization. Treatment with DHEA increased antibody titers at day 14 after immunization. Mice were challenged with live VEE virus at day 21, and viral titers were plaque assayed in chicken embryo fibroblasts from days 2 to 5 post-infection. After the challenge, viremia decreased on day 2 and brain virus levels were reduced at day 4 in mice treated with DHEA. These results suggest that DHEA treatment could enhance the efficiency of immunization against VEE virus in mice. PMID- 11787269 TI - [Serum immunoglobulin E levels in patient with fatty liver, whether associated with alcohol consumption or not]. AB - It has been reported that total Immunoglobulin E levels (IgE) are elevated in patients with liver damage (fatty liver), associated with alcohol consumption, but the mechanism responsible for this increase is not completely understood. The objective of this investigation was to determine serum concentrations of IgE in patients with fatty liver, associated or not with alcohol consumption. During the period of February-August 2000, a total of 756 patients attended the outpatient Gastroenterology Service of the University Central Hospital "Antonio Maria Pineda" in Barquisimeto, Venezuela. Of these, 150 were diagnosed as suffering from fatty liver, but only 63 patients fulfilled the inclusion criteria. The IgE was determined by Photoemission Immunometric Enzyme Immunoassay (High Resolution Amplified Chemoluminescence). IgE serum levels were higher in patients that consumed alcohol (low risk consumer, mean 586.42 +/- 779.74 UI/mL; consumer at risk, mean 329.31 +/- 358.13 UI/mL) in comparison with abstainers (mean 77.51 +/- 56.95 UI/mL) (p < 0.05). There was no relationship between IgE levels and the severity of hepatic steatosis. IgE may be considered a biochemical marker for fatty liver associated with alcohol consumption. PMID- 11787270 TI - [Viral agents in patients with infectious processes of the central nervous system]. AB - Local statistics report a great number of cases of neurological diseases of unidentified cause. The purpose of this research was to determine the presence of viral agents in patients with affection of the central nervous system, in Zulia State, Venezuela. In different health centers throughout the state, we collected 129 randomized samples of cerebrospinal fluid (CSF) and serum from patients ranging from 1 day to 41 years of age, showing symptoms of CNS disease and whose bacteriological test resulted negative. The serum/CSF albumin ratio was determined to exclude contaminated CSF samples, thus 54 optimal samples were obtained for the research. We determined serum IgM and CSF IgG specific for Venezuelan equine encephalomyelitis (VEE), Herpes simplex (HSV), Epstein Barr (EBV), Dengue, Rubella and Measles virus, through ELISA and indirect immunofluorescence techniques. Of the 54 samples studied, 33 (61.11%) were positive. %). The etiological agents implicated were VEE 14 cases (42.42%); HSV 11 cases (33.33%); EBV 5 cases (15.15%) and Dengue 3 cases (9.09%). We did not detect Rubella o Measles. Regarding the age distribution, the most affected group was that of children under 12 (83.34%). We analyzed the clinical manifestations and the CSF characteristics and did not find differences suggestive of an specific etiological diagnosis, even though certain signs could be considered early indications of CNS alterations due to viral causes. Our study shows that a large percentage of CNS affections of unknown etiology are produced by viral agents, indicating that in our region, most of this cases are not registered. PMID- 11787271 TI - [Glucose/insulin response to a glucose overload in subjects at risk for type 2 diabetes]. AB - With the purpose of determining how certain risk factors for type 2 diabetes such as family history of diabetes, obesity and dyslipidemia, affect the glucose insulin response to a glucose challenge, 135 individuals (77 women and 58) men were studied. Their ages ranged from 20-68 years, their basal glycemic values were less than 110 mg/dL but they were considered at risk for diabetes due to the presence of one or more of those factors. We found that the presence of those risk factors did not affect the glycemic response in any case. However, the basal insulin levels as well as the post-challenge values were increased significantly (p < 0.0001) by the presence of obesity in men as well as in women. Dyslipidemia increased the basal and post challenge glucose insulin values only in men (p < 0.002). The coexistence of obesity and family history of diabetes provoked a decrease in the basal insulin levels as well as in the insulin response to glucose. We conclude that, without alteration of the glycemic response, the presence of risk factors as obesity, dyslipidemia or family history of diabetes leads to basal hyperinsulinemia, as well as glucose stimulated hyperinsulinemia, however the coexistence of obesity and family history of diabetes, is responsible for a deficit in the insulin secretion by the pancreas. PMID- 11787272 TI - [Examination of the power of families taking care of patients at home at peace]. AB - OBJECTIVE: We examined the power of families who take care of a patient at home. We wanted to know how much caring power patients needed to stay at home at peace. PATIENTS AND METHODS: The subjects were 150 patients who visit the hospital for day care or are taken care of at home under our management. We examined their age, sex, main disease, the points of their families power for their care, the assessment of how peaceful at home, use of care services, and special things. RESULTS: Most of the patients were in their 80's or 70's. Stroke was the main disease. The most care grade are second grade. Higher care grade are smaller number. About 50% of the families paid for care services. The assessment of low care grade patients did not depend on the power of the families. But the assessment of high care grade patients did depend on that. We concluded that it is difficult to take care at home of high care grade patients who does not have some powers on families for his care. If the patient and his/her family want to use care services, they have to pay 10% charge. It is difficult to alleviate the burden they pose on their family. PMID- 11787273 TI - [Drug consultation for a terminal cancer patient at home care-management of dyspnea and pain by morphine]. AB - We studied on the points of that a management of dyspnea and pain by morphine for a terminal cancer patient at Home care. It was suggested that a necessary on management of symptoms for a terminal cancer patient before home drug therapy, a education to patient and his family by drug consultation before and after home drug therapy, a confirmation of dyspnea and pain for a terminal cancer patient from one drug to the next, and a importance of communication between medical staffs. PMID- 11787274 TI - [Management of medical practice at home]. AB - We present here how medical practice is managed at the patients home. Medical care at home is conducted in conjunction with a variety of professionals who provide health care in the community. The use of computers allows us to easily download information, and transfer it from the clinic to community services. Fluid replacement, total parenteral nutrition, palliative treatment of pain in cancer patients, management of urethral catheters, and other skills that are carried out at home would be stated. PMID- 11787275 TI - [Factors that enable the patients to live their life till death at home by controlling cancer-pains with continuous subcutaneous injection of opioids-case reports of 3 patients with a terminal cancer]. AB - Recently, it is gradually getting easier to change a life-style of the patients with cancer-pains from the conventional hospitalized way to the home healthcare system, because of the progress in technique of reducing pains and symptoms and because of prevalence of visiting nurse system. Home healthcare system or hospice is aimed at the improvement of the quality of life (QOL) of the patients. We had 3 patients who died at home after home healthcare service and whose cancer-pains were well controlled till their death at home by continuous subcutaneous injections of opioids (painkiller) when these patients could not take oral medications any more. Therefore, in order to determine the factors that enable the patients to live the terminal stage of their life at home until death by controlling their cancer-pain with continuous subcutaneous injections of opioid, we examined 3 patients who died of cancer at home under a good pain control. The subjects of the present study were 3 patients, who initially had oral or rectal medication of opioid for their pain control, eventually switched to subcutaneous injection of opioid and then died at home under a good pain control between April 1998 and December 2000. We collected all the information through nursing diaries, regarding painkiller care, and interaction of the patients, their family members and other people, and discussed the factors which enabled to maintain a good pain control in these patients at home by continuous subcutaneous injection of painkiller (opioid). As a result, the following 7 items were notified as the factors common in these 3 patients. 1) The patients themselves understood the diagnosis of their diseases and symptoms and could openly discuss the issues such as "how the patient and his/her family would like to live his/her life from now on" among family members, and also between family and medical associates. 2). The patients received detailed explanation of continuous subcutaneous injection at the time of admission to the hospital and chose to receive the continuous subcutaneous injection with their own will. 3) The patients had no other painful symptoms except cancer pains or had them well controlled if they had any, and had much stronger desire to live their life at home than above all. The family member agreed with the patients and respected their choice. 4) The family members had enough nursing capability, so they could properly handle medications and medical equipment as well as they could take care of the patients. 5) Both primary care physicians and visiting nurses had enough knowledge of home healthcare service for painkiller, and were able to frequently interact with the patients and their family in order to reduce their pains. 6) Visiting nurses supported the family by 24 hr-system and assisted the family in nursing the patients at home without worry. 7) Pharmacists also participated in the home healthcare system, thus, they could smoothly provide and manage opioids without any trouble. PMID- 11787276 TI - [The examination of usefulness of the disposable pump in case of cancer pain relaxation and the economic problem]. AB - Recently, an increasing number of cancer patients being taken care of at home has been able to use morphine to treat their pain by themselves. The most suitable administration method for individual patients-oral, intravenous, subcutaneous or depository--is being investigated. When oral intake becomes difficult, the subcutaneous via of administration is best option because it is the less dangerous and easier to use compared with the other two options. These are also thought to be less useful because it is difficult to judge the exact dosage. The use of pumps might be an economic problem to some patients. We will examine this problem. PMID- 11787277 TI - [Features of home care for patients with advanced breast cancer]. AB - We examined the features of home care for patients with noncurable breast cancer. The patients were 21 women with advanced breast cancer who entered the home care program between April 1987 and May 2001. The first feature was that their young age: six of them were in their forties, five were in their fifties, and the mean age was 57.4 years old. The second feature was that the period home care was provided was long. The mean duration of home care from the beginning to their death was 143 days. This was because the period of sickness and the period until the breast cancer's relapsing were both long. The mean period until the relapse was 2.3 years, and the mean period of sickness was 4.1 years. The third feature was the great variety of symptoms. It is this cause that there are a lot of metastasis organs. The fourth feature was that no special treatment, such as infusion therapy, was really necessary to alleviate the symptoms. Pain control was important because there were a lot of patients whose main complaint was pain. However, pain could be controlled with morphine. In conclusion, if it is excluded not to have the nursing power because the age is generally young, home care can be comparatively offered to the person who has an advanced breast cancer for a long term. PMID- 11787278 TI - [A case report of the patient at a terminal stage of stomach cancer, who had a visiting nurse]. AB - We have started the visiting nurse system in our Kimitsu Central Hospital since September 1990, and have currently had 33 patients with 4 visiting nurses as of February 2001. Out of these 33 patients with the visiting nurse system, 9 patients are at a terminal stage of diseases. In the present study, we reported here a case of a 63 year-old female patient, who was at a terminal stage of stomach cancer and wished to have a regular home life, having a visiting nurse at home. The patient was not informed of her diagnosis as a cancer, but was convinced of her symptoms by her primary care physician that she was under a good care. Meanwhile, the patient showed less pain than that she was expected to have as a patient at the terminal stage of cancer. A daughter of the patient (actual caretaker) was first considering of hospitalization as an inpatient. However, since the patient strongly desired to stay and get care at home, the caretaker started a dual life of taking care of her mother at home and of raising children in parallel, in aware of a case of pronouncing death at home. While the patient's condition was relatively stable, the good quality of life (QOL) was maintained as she could make a trip of one-night stay. As the symptom progressed, however, the caretaker had a high anxiety with a pressure of accepting her own mother's death. On the other hand, a visiting nurse, who understood the patient's strong desire to stay at home and live her life as usual, also assisted in reducing the caretaker's high anxiety. Therefore, the visiting nurse basically assumed one possibility that the patient would die at home, but also prepared for the another possibility that the caretaker could choose to send her mother back to hospital whenever she felt her limit for being a caretaker. Moreover, the visiting nurse supported the patient and her family with an encouragement that they could live their favorable life till the end. As a result, the caretaker could continue to keep the patient at home, although she had a tremendous fear about taking care of her at home. When the patient's condition suddenly changed and got worsened, however, the caretaker desired to have her mother stay and get medicated in the hospital. Thus, the patient was sent to our hospital by ambulance. Although the caretaker did not have her mother die at home under her direct care, she recognized the great advantages in having a visiting nurse, who really assisted them well. Thus, it was confirmed that participation of a visiting nurse in the home healthcare could give the patient and her family a better, satisfactory life till the end. In general, although the patients or their family members wish to stay home and to have a home healthcare service, their desire or mind can be easily changed according to their situation. Especially in a case of the patient at a terminal stage, the family can be easily influenced by the condition of progression of the disease. One of the major roles of visiting nurses is always to understand the feelings of the patients and family and to prepare for the best as they can. PMID- 11787279 TI - [A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system]. AB - AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions. PMID- 11787280 TI - [How to support the death at home]. AB - Forty-three patients who were taken care of at home were divided into three groups according to the place of their death to examine the cause of death at home and to improve the home care service, especially for supporting the death at home. Group A included 15 patients who died at home, group B included 22 patients who died at the hospital and group C included 6 patients who were transferred to our hospital by ambulance to confirm they were dead. In group A, 8 patients died from cancer, 5 from old age, 1 from chronic heart failure and 1 from Wernicke's encephalopathy. In group B, 8 patients died from pneumonia, 3 from other acute diseases, 4 from cancer, 4 from other chronic diseases. In group C, 5 patients died from old age and 1 from cancer. After the home care service was changed to 24-hour support, the number of patients who died at home increased from 1 to 14, and the emergency transfer by ambulance decreased from 5 to 1. The patients with chronic and gradually deteriorating conditions, such as cancer and aging itself, tend to die at home and this is effectively supported by the 24-hour home medical care service. PMID- 11787281 TI - [On total care we have learned during home care hospice study trips in USA--from the experiences of 8 year times visits to America with medical students for practice]. AB - Every year since 1993, as a part of the medical education program of Osaka University, I have taken 10 or more medical students and others to hospices in the USA to study hospice and home care during two weeks. We visit patients and interview them. Palliative care treatment is by definition care treatment designed to relieve pain and distress, pain and symptom management is essentially important. It was very impressive for us to see that in American hospices total care was provided by many kinds of professionals working as a team. Socio psychological and spiritual care played important roles in total care, which was provided not only to the patients but also to the families, care-takers, and bereaved families after death. We saw home was the best and most natural place for them. I think we have much to learn from these experiences, such as that doctors and nurses are not bosses, but equals among professionals. Also, that home care is not a temporary place in an institution, and that there are many terminal illnesses, besides cancer and AIDS, for which patients require home care. PMID- 11787282 TI - [Percutaneous trans-esophageal gastro-tubing (PTEG): experience of home care with a long-term PTEG]. AB - PURPOSE: Percutaneous trans-esophageal gastro-tubing (PTEG) was developed as a new method of esophagostomy for drainage and feeding. It is especially easy to create a PTEG for patients in whom it is difficult to perform a percutaneous endoscopic gastrostomy (PEG). Here we report a satisfactory experience with a patient with dysphagia for whom we improved the patient's QOL with PTEG. The patient suffered from terrible dysphagia due to Parkinson's disease and was in the postoperative recovery status after undergoing a gastrectomy for gastric cancer. PTEG allowed the patient to receive further long-term medical care at home. CASE: The patient was a 74-year-old man with severe dysphagia due to Parkinson's disease and had a residual stomach as a consequence of a gastrectomy. He had to continue receiving long-term enteral nutrition at home, however it was difficult to create a PEG. We therefore decided to use a PTEG. MATERIALS/METHOD: For the PTEG, a rupture-free balloon (RFB) catheter for enteral nutrition was used. First, an RFB was inserted through the nose into the esophagus and inflated. The RFB was punctured percutaneously aided by ultrasonography and conventional fluoroscopy. Then, a guide wire followed by a dilator with a sheath were inserted. Finally, an indwelling catheter was inserted into the digestive tract through the sheath. REMARK: PTEG using an RFB catheter was a safe, simple and less invasive method; it enabled the patient to continue receiving further medical treatment at home without major complications for a long term. PMID- 11787283 TI - [The effects of percutaneous endoscopic gastrostomy feeding in patients with swallowing disturbance]. AB - BACKGROUND AND PURPOSE: Because the number of patients who need home healthcare has recently increased in Japan, Percutaneous endoscopic gastrostomy (PEG) will soon become more popular. This study aims to examine the effects of enteral alimentation via PEG. MATERIAL AND METHODS: The subjects were 18 patients who underwent PEG instead of receiving total parental nutrition (TPN) (TPN-to-PEG group), 13 patients who underwent PEG instead of receiving enteral nutrition through a naso gastric tube (NG-to-PEG group), and 11 healthy volunteers (control). Morphological changes of the small bowel mucosa and activities of daily life (ADL) after PEG were also investigated. RESULTS: In the TPN-to-PEG group, the serum level of total protein and albumin, length of duodenal villi, ration of positive proliferative cells, width of duodenal microvilli and ADL markedly increased. In the NG-to-PEG group, body weight and ADL were markedly improved after PEG. CONCLUSION: Nutrition via PEG is superior to TPN or enteral nutrition with an NG tube. I conclude that PEG will become the first choice for improving nutrition in patients with dysphasia and will contribute to continuous enteral nutrition for home care. PMID- 11787284 TI - [Discharge planning for home care]. AB - The department of medical social work and discharge planning was established in the University of Tokyo hospital to ensure that patients would receive proper care at a right place. The discharge planning team consists of a physician, a medical social worker and a home care coordinator. The home care coordinator, who coordinates with the home nursing station and the primary care physician, is effective for advance of home care. The role of the home care coordinator is to relieve patients of their anxiety about home care. As a result, the number of home care patients has gradually increased. PMID- 11787286 TI - [Evaluation of the new pump for home parenteral nutrition Terumo Cafty]. AB - This study was undertaken to evaluate the usefulness of 'Cafty' which is a new infusion pump system for administering home parenteral nutrition (HPN), recently launched by Terumo Corporation. We used 'Cafty' in two patients and found it has more advantages than the existing pump with regard to the following points: 1. Cafty is provided with a display and alarms that indicate pump troubles such as emptiness, occlusion or mis-operation. 2. It is easier to carry because of its smaller size (width 80 mm x length 132 mm x thickness 33 mm) and its lighter weight (320 g). 3. While Cafty operation using a cassette-type tubing and plain control panel to simpler the flow rate accuracy is not reduced. In conclusion, Cafty is better than the existing HPN pump from the viewpoint of safety, portability and easiness. PMID- 11787285 TI - [The new portable system for home enteral nutrition, Portermate, made a patient possible go out for a long time: report of a case]. AB - The patient, who is received home enteral nutrition (HEN) for a long time in a day, has problems on moving all days. Now, we tried Portermate, which is new portable devices for HEN, in his clinical care. The patient is chronic pancreatitis, and his clinical problems becomes to be worse after he ate. He was under total enteral nutrition via jejunostomy. His clinical complications were almost controlled after HEN, but he has a few complains receiving enteral nutrition. He would not move easily, for an old HEN system was not compact to move. Portermate made him go everywhere he wanted any time. It extremely improved his QOL under HEN. He continues to use Portermate. PMID- 11787287 TI - [Factors in popularizing home nutritional therapy (HNT) in Japan-analysis of nurse's awareness]. AB - Home nutritional therapy (HNT) is not popular in Japan as compared with American countries. The purpose of this study was to clarify the role of nurses in popularizing HNT. We sent out questionnaires to 469 nurses working at the O University affiliated Hospital, and got 265 responses. As a result, the following two factors were considered to affect the popularization of HNT. 1. Nurses had only a superficial knowledge of the activities of the nutrition support team (NST), and medical care by NST had not been spread. 2. In HNT, there were several gaps between ideals and the real role of nurses. PMID- 11787288 TI - [Evaluation of patients who received treatment (procedures) that involved minor surgical techniques at home]. AB - We retrospectively examined the clinical records of 24 patients who underwent minor surgery under local anesthesia among 207 who were taken care of at home by our staff, from December 1986 to March 2001. There were 17 men and 7 women. Their mean age was 74 years and the range was 50 to 92 years old. The treatment consisted of central vein catheterization in 14 patients, skin suture in 6, subcutaneous implantation of port establishment and epidural catheterization in 3 patients each, treatment of anus, thorax centesis, skin tumor resection, and treatment of bed sores 2 patients each, wash of thorax, ovarian cyst centesis, and transcutaneous trachocentesis 1 patient each. A relationship of trust with the patient and the family and informed consent were thought as the most important aspects regarding treatment involving minor surgery provided at home. PMID- 11787289 TI - [Problems regarding palliative home care for end-stage cancer patients after the enforcement of the care insurance system]. AB - Since in a home care nurse station the arrangement of personnel is planned to carry out patient's home care in accordance with the individual patient's Care Plan, to provide palliative home care to end-stage cancer patients who frequently require extraordinary visits, it is necessary to employ full-time nurses. On the other hand, to make ends meet there must be at least two full-time nurses for every seven end-stage cancer patients in a home care nurse station monthly. However, a home care nurse station taking care of seven end-stage cancer home patients monthly is very rare. According to these circumstances only several special home care nurse stations are able to provide palliative home care to end stage cancer patient; thus, palliative home care for such patients is generally provided by hospital or doctor's office staff members. Therefore, if the authorities concerned intend to accelerate to care the end-stage cancer patient at home, several additional charges which are able to be claimed in ordinary home care nurse station must be able to be claimed in hospital or doctor's office in the same way. PMID- 11787290 TI - [The use factor of the long-term care insurance after enforcement half a year]. AB - PURPOSE: The purpose of this study was to examine the factors involved in the low usage of home care services in Japan half a year after their enforcement. METHOD: Questionnaires were mailed to the 1,500 senior citizens residing in H city Osaka who were using the home care services covered by the long-term care insurance system. Of the 1,500, 888 responded (59.2%). RESULTS: Of the 888 respondents, 70.7% were women, with a mean age of 82.0 +/- 7.2 years; 33.2% were living alone and 19.3% were living with their spouse. The rate of use was higher than the national average. Use amount of money. Then, when yen 10,000-15,000 were exceeded that the number of users is halved. Of the service control factor, 40% were economical burden, 32% were no-necessary of service, 27% were feeling of resistance to staff and shortage of information, 7% were complicated proceduring and without service. The rate of use and significant relation were seen, "senior citizen only family, short-stay service, home helper service, day care service, and the senior is dementia". PMID- 11787291 TI - [The care insurance and the patients of at home care]. AB - Thirty-one patients used the at-home nursing care service provided by our hospital. However, they were also taken care of by old family members, mostly 60 years old or more, thus only 23.8% of the maximum Care Insurance was used. The average insurance, for the service is 6,312 yen, which does not increase according to the level of care the patient required. Especially, the expenses regarding the home bathing service, which is the most used, have doubled since the Care Insurance started. The family of most patients may not be able to pay more than 10,000 yen every month for the care of old and handicapped people. The increased expenses can become an obstacle regarding the promotion of at-home care. PMID- 11787292 TI - [One-year experience with the care insurance system in Kadoma City, Osaka Prefecture]. AB - A year has passed since the care insurance system started. Even though people have pointed out various kinds of problems, the number of users has gradually increase and lots of them have reported satisfaction. At present, there are about 2 million and 600 thousand people who have assessed the care grade, but about 600 thousand people who do not use care service. Although the patients and their families do not want to use the care service system, caremanagers can not leave them as they are. The topic that caremanagers have to take care is how to support them. PMID- 11787294 TI - [Nutritionist's role, attitude and training for home medical care]. AB - It has been a year since the Kaigo (home medical assistance) insurance started for people who need an assistance in their daily living. Because of a national health insurance policy was partially amended in October 1994, a nutritionist's performance based on the home medical care guideline has been graded by scoring in points. According to the facts collected in 1998 by the department of nutrition at National Health Insurance, it appears that only the 4 percent of hospitals have executed training for their nutritionists. Although providing a nutritional assistance to patient is an essential part of home medical insurance policy, it is rather difficult to collect data with such a lack of low execution of nutritionist training by hospitals. We simply could not measure how a home nutritional assistance has been effective to patient. We therefore ought to develop perspectives of home health nutritional management, and we also do review a current nutritionist's role, attitude and training for home medical care in terms of how a nutritional assistance to a patient to be successful. PMID- 11787293 TI - [Differences between gynecological cancer patients taken care for at home and those taken care for at the hospital]. AB - Thirty-five patients with end-stage gynecological cancer, twelve taken care for at home care and 23 taken care for at our hospital, were compared. The life span after recurrence was significantly (p < 0.05) longer in the group taken care for at home. The number of persons living with the patient was also significantly (p < 0.01) larger in the group taken care for at home. Moreover, the hospitalization in the end stage of the disease was significantly (p < 0.01) shorter in the group taken care for at home. The average hospitalization in the end was for 6.5 days. Four patients died at their home. Average period the 12 patients stayed at home was 52.7 days. Following matters are important in order to provide home care. 1. We must know the biological characteristics of the cancer. 2. It is important that it does not lose the timing to which shift to the home care, keeping good doctor-patient relationship. 3. Limit of the therapy against cancer and importance of treatment at home should be carefully and clearly explained to the patient. PMID- 11787295 TI - [Indication of home oxygen therapy for terminal cancer patients--comparison with present standards--as the result from investigation of our patients and questionnaire survey to home care doctors]. AB - As the result of the observation of our patients and a questionnaire answered by home care doctors, we think it is necessary to establish new standards for home oxygen therapy, based on the characteristics of terminal cancer patients and to put great emphasis on the QOL of patients. PMID- 11787296 TI - [The advantages and disadvantages of administering anti-cancer chemotherapy at home]. AB - We analyzed the effectiveness of anti-cancer chemotherapy administered at home. Continuous hepatic arterial infusion (HAI) of 5-FU (250 mg/day) for unresectable liver metastases of colorectal cancer (129 cases) and systemic administration of 5-FU and CDDP (FP therapy) as a palliative treatment or for recurrent cases of colorectal cancer (145 cases) were evaluated. The response rate for HAI was 59.7%, and 50% survival according to the outcome of HAI was CR: 765 days PR: 607 days NC: 233 days and PD: 146 days. The residual life span of patients who showed CR or PR was significantly prolonged. The occurrence of complications from HAI was 15.1%. On the other hand, the response rate was 19.3%, and 50% survival was 292 days. The one-year survival rate was 38.7%. The mean duration of this chemotherapy and the mean stay at home were 188.2 days and 237.8 days, respectively. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS accounted for 74.5% of all cases. Those with a PS grade 3 or 4 accounted for only 1-4% of the patients. Finally, both chemotherapies could be continued at the outpatient clinic or at home. PMID- 11787297 TI - [A case of short-bowel syndrome treated with parenteral nutrition at home--its effectiveness on improving nutritional status and quality of life]. AB - Although the effectiveness of home parenteral nutrition (HPN) for short-bowel syndrome has already been demonstrated, there are some patients who suffer from severe malnutrition because they cannot be treated with this therapy. We here report the case of a patient with short-bowel syndrome due to massive bowel resection after superior mesenteric artery thrombosis. As she had not received adequate nutritional support, she became severely undernourished and her activities of daily life were very limited during two years after the operation. She was introduced to our department and HPN was initiated. Her nutritional status and quality of life rapidly improved. Thus, we further confirmed the effectiveness of HPN for ambulatory patients with short-bowel syndrome. It is important to take measures not to make patients with short-bowel syndrome, suffering from severe malnutrition without adequate nutritional support, HPN. PMID- 11787298 TI - [Troubles inherent to long-term home parenteral nutrition (HPN) and the use of technologies to improve communication between medical institutions and patients]. AB - The continuous advance of technology has contributed to the improvement of the quality of life of patients under long-term home parenteral nutrition (HPN). But the longer the patient stays home, the higher the risk of many kinds of troubles. We designed an HPN system in June 1999, which uses E-mail for patients and to contact with each other (including the patient's family) and to prevent troubles from worsening. We describe the case of a patient which shows the efficacy and usefulness of our system, which makes use of the Internet, video mail, voice mail and electric medical records. PMID- 11787299 TI - [Feeding methods for long-term bedridden patients with dysphagia under home health care--percutaneous endoscopic gastrostomy (PEG) and intravenous hyperalimentation (IVH)]. AB - We began home health care in our hospital in 1992, and the total number of patients under home health care has reached 380 so far. We report 12 bedridden patients with dysphagia, who have obtained nutrition using two feeding methods. The patients are 7 men and 5 women, with a mean age of 81.4 +/- 8.8 years. The diseases in these patients include cerebrovascular diseases, Parkinson's disease, and senile dementia of the Alzheimer type. The feeding methods include swallowing after swallowing training, percutaneous endoscopic gastrostomy (PEG), and intravenous hyperalimentation (IVH). We have fed these patients by combinating these three methods. The patients fed by swallowing and PEG, swallowing and IVH, and PEG and IVH are five, five and two, respectively. It is very important for bedridden patients to eat and swallow food by themselves, even if the amount is extremely small. Although swallowing training has been performed, the amount of food is not sufficient for life support. Therefore, additional feeding by PEG or IVH is necessary. Sufficient nutrition through a variety of feeding methods is important for patients under home health care. PMID- 11787300 TI - [Current situation and problems inherent to long-term home medical care as compared with medical care provided in nursing homes]. AB - We compared 18 patients under long-term home medical care and 11 patients who entered a nursing home after receiving home medical care, to analyze the factors thought to influence continuation of home care. There was no statistical difference between the mean age of both groups, but the mean age of main caretakers in the former (mean 59 years old) was lower compared with that of caretakers in the latter (mean 70 years old). There were various reasons for them to enter a nursing home after receiving home care. Five of the 11 patients entered the nursing home after long-term hospitalization in spite of no deterioration in their degree of handicap at discharge. We think the long-term hospitalization may reduce the motivation of caretakers. It is indicated that the age of caretakers and ability, especially motivation to provide care are important factors to continue home medical care. PMID- 11787301 TI - [Characteristics of hemiplegic outpatients with stroke who try to remove their clothes unnecessarily]. AB - We have observed that patients who suffer from hemiplegia after a cerebral stroke, tend to remove their clothes although it is not necessary to change them while they are in hospital. Not only does this activity make it difficult to manage the ward and carry out rehabilitation, but it also often becomes problematic for home care once the patient has been discharged from hospital. However, there have been no previous reports on this activity. In this study, we examined the characteristics pertaining to clothes removal in hemiplegic patients under home care. The subjects were chronic-stage, cerebral stroke hemiplegic patients hospitalized in the rehabilitation ward of this hospital since the first initial seizure. Once it was established that environmental factors, such as room temperature, were not the primary reason for the patients to try to remove their clothes, the patients were closely monitored and the circumstances under which they tried to remove their clothes (location, time and type of clothes removed) were recorded to examine the relationship among age, sex, side affected by paralysis, higher cortical function, motor paralysis and ADL. Thirty-five percent of the patients, mostly women, usually tried to remove their clothes and the tendency was for them to incompletely remove their tops without reason while they were confined to bed or sitting on the bed. This activity was also prevalent among patients with accompanying diminished intellectual function, left hemiplegia, and left unilateral spatial agnosia. The acquired level of ADL by FIM in the group in which this activity was observed was low, except regarding meals. Thus, it was inferred that in stroke hemiplegic patients being taken care of at home the removal of clothes was related to a diminished intellectual function or ADL, which suggested the importance of family guidance based on observations of the patient's behavior in the ward. Targeting a greater number of subjects, we would like to conduct further studies on home-care measures to deal with this activity. PMID- 11787302 TI - [Problems inherent to the care of patients with ALS]. AB - A questionnaire survey was conducted in September 2000 to clarify the actual state and problems inherent to the care of patients with amyotrophic lateral sclerosis (ALS). The subjects were members of a patients' association, and 176 members answered the questionnaire (response rate. 64.9%). Patients being taken care of at home accounted for 76.7% of those who answered the questionnaire and those under mechanical ventilation (MV) at home for 40.3% of respondents. Compared with the results of the same survey administered by the patients' association in 1992 and 1996, the figures showed an increase of the patients being taken care of at home. Of the subjects who were receiving domiciliary services under the long-term care insurance system introduced in April 2000, those who considered the services had improved under the new system accounted for 44.2% of the respondents, and those who thought the services had worsened for 25.0%. The latter percentage included a greater number of patients under MV or who were using an aspirator and those with overworked caregivers. Moreover, the burden for the caregiver did not necessarily decrease when the patient was admitted to hospital, because attendance by the caregiver or additional costs for services were required. The new insurance system is thus considered to be inadequate and unsatisfactory for seriously disabled people, such as patients with ALS. PMID- 11787303 TI - [Current spread of HPN and HEN: issue for making choice in home care]. AB - Recently a number of patients have received home enteral nutrition (HEN) as well as home parenteral nutrition (HPN) in Terumo's home healthcare network 'Home Joint'. This study was undertaken to compare the patients who received HEN with those who received HPN. 1. HPN patients in 2000. Number: 1,789 (45% females), age: 0-101 (mean: 66 years old, 48% over 70 years old), diagnosis: cancer 54%, therapeutic periods: 0-916 days (mean: 80 days). 2. HEN patients in 2000. Number: 736 (40% females), age: 1-101 (mean: 50 years old, 33% over 70 years old), diagnosis: Crohn's disease 44%, therapeutic periods 0-1,618 days (mean: 183 days). 3. Adoption of HPN and HEN in home care agents. HPN only 66%, HEN only 24%, both HPN and HEN 10%. It suggested that following two issue take place against making choice of HPN or HEN in home nutrition care. 1) Adoption of both HPN and HEN in more clinics. 2) Establishment of the guidelines for systematic HPN/HEN choice. PMID- 11787304 TI - [Necessity of co-operation of the community medical system based on the results from the survey by questionnaires-participation of the home healthcare and/or hospice systems in southern Tama community hospitals]. AB - Home Care Division of Fujisawa Pharmaceutical Co. Ltd. has been providing the local public with the following services: 1) providing aseptic medicines prescribed in the clean room, 2) renting the infusion fluid pumps, and 3) supporting the community cooperation in healthcare services. Last year, we surveyed questionnaires to the public users (patients and caretakers) of these services, in order to understand the actual status of patients after changing from conventional hospitalization to the home infusion therapy (HIT). From the results of our present survey, it was found that the patients and their family members had positively accepted HIT, while 61% of the HIT users exhibited a strong anxiety in their skills and methods of HIT. Moreover, it was also shown that 61% had other means of nursing and treatment in addition to HIT, indicating a great financial burden on the families. Among them, 69% of the HIT users considered that visiting nurses and primary care physicians were the best co operators, and changed their conventional healthcare system (hospitalization) to HIT. However, the home caretakers showed a high anxiety in their skill in the home healthcare system, specifically HIT, which was generally highly dependent on the medical care, Thus, a good relationship and co-operation with visiting nurses and primary care physicians was one of the major factors for the users to decide to choose HIT instead of their old medical hospitalization. Therefore, in order to make HIT more useful and widely prevail, it is concluded that establishment of the co-operative systems within our local community, where visiting nurses and primary care physicians can easily provide the patients and their family with professional suggestions, advice and actual care whenever the home caretakers need them. PMID- 11787305 TI - The public health approach to motor vehicles, tobacco, and alcohol, with applications to firearms policy. AB - The public health approach that has been used to reduce problems caused by motor vehicles, tobacco and alcohol is applied to firearms policy. Manufacturers try to focus prevention efforts on the user rather than the product, and promote education and law enforcement policies directed toward the consumer. Public health efforts emphasize the systematic collection of data, scientific inquiry, and a multi-faceted policy approach that includes modifying the product and the environment. The endeavor to reduce gun violence is part of the general and continuing public health struggle to reduce harms caused by consumer products. PMID- 11787306 TI - The British Labour government's reform of the National Health Service. AB - The recent general election in Britain saw healthcare as the dominant issue amongst voters. The victorious Labour Party responded to this concern with a set of reforms designed to introduce greater private-sector involvement in the delivery of healthcare. These reforms are ill-thought-out. The standard of care in British private hospitals is below that found in public hospitals, whilst new contracting arrangements are likely to increase the administration costs within the system. Faith in private-sector management techniques is misplaced at a time when the real problem facing the NHS is that of capacity. The Labour Party is also committed to redefining some aspects of healthcare as a personal responsibility and not a right, moving Britain towards a more market-based healthcare system. PMID- 11787307 TI - International tobacco control: a focus group study of U.S. anti-tobacco activists. AB - Massachusetts tobacco control activists participated in focus groups to explore their knowledge, beliefs, and attitudes regarding international tobacco control. Initially, each of three focus groups ranked this issue at or near the bottom of important tobacco control issues. Participants ranked ten message concepts for their ability to motivate politically active Americans to contact a government representative about international tobacco issues. The top four message concepts dealt with deliberate marketing of cigarettes to children, dramatic increases in global mortality due to smoking, American hypocrisy in being the world's largest tobacco exporter, and use of overseas profits to finance youth-oriented marketing in the U.S. The rankings revealed little initial concern about U.S. diplomatic pressure to force foreign nations to open up their markets to American tobacco products. Yet during the subsequent discussion this was among the message concepts the generated the most outrage. This suggests that international tobacco control issues would resonate among U.S. opinion leaders once the facts were presented to them through a media advocacy campaign. PMID- 11787309 TI - The changing relationships of epidemiology and society: the Robert Cruickshank Lecture. PMID- 11787308 TI - The resurgence of sexually transmitted disease in China. AB - In the early years following the Chinese revolution in 1949, the Chinese mounted mass campaigns against the preventable communicable diseases including the venereal diseases. These were characterized by mass education, a national health insurance system, training and dispersion of the "barefoot doctors," elimination of prostitution, emancipation of women, and full employment. By 1996, the Chinese claimed that they had virtually eliminated venereal diseases. This was confirmed by western visitors in the 1970s. However, following the economic reforms which began in the 1980s, sexually transmitted diseases reappeared. Later, HIV infection appeared, and STDs today constitute a major public health problem in China. This resurgence parallels the privatization of the economy, the breakdown of the national health insurance system, the return of prostitution, and other factors. PMID- 11787310 TI - What I need to know about anthrax today. AB - The US Department of Defense has been concerned about the use of anthrax as a biological weapon by an enemy on US troops for a number of years. This is the reason why the military has embarked on a vaccination program for its forces deployed to regions of the world, which are considered high-risk areas. These areas have been in the Southwest Asia-Persian Gulf region as well as the Korean Peninsula. Many intelligence personnel have also been concerned about the possibility of biological agents being used by terrorists in the Continental United States. The recent anthrax incidents in Florida and elsewhere in the United States have significantly heightened concerns along these lines, especially following the terrorist attacks on the World Trade Center and the Pentagon on September 11th. The death of a Florida businessman, identification of infection in one of his co-workers, evidence of exposure and in some instances, cutaneous infection in some others, as well as evidence of contamination in their buildings, raised further concerns of the possibility of terrorist activity using biological warfare in this country. It is somewhat ironic that a disease that you probably haven't heard about since medical school has become the focus of national attention. Our goal in this communication is to refresh your understanding of what anthrax is and what you need to know about it today since anthrax is counted among the weapons of mass destruction. As a member of the medical profession, you will need to know what to look for in patients and how to treat them if they are contaminated with this biological agent. You will also have to serve as the "front line" of the public health system and alert the police and public health agencies. PMID- 11787311 TI - Spontaneous resolution of a giant pulmonary bulla. AB - Giant bullae occur most often in individuals who chronically inhale tobacco smoke. The natural history of these bullae is unpredictable, although the majority of them increase gradually in size and cause worsening respiratory function. Complete spontaneous resolution of a giant bulla is a rare occurrence, with only eight cases reported in English literature. Most of the cases of spontaneous resolution of giant bullae are thought to have resulted from an infectious process leading to closure of the communication between the airways and the bulla. However, resolution of a bulla has been associated with adenocarcinoma of the lung. PMID- 11787312 TI - History of tobacco use among Kentucky women diagnosed with invasive cervical cancer: 1997-1998. AB - An association between cigarette smoking and cervical cancer has been demonstrated by numerous epidemiologic studies. However, just because there is an association does not mean that there is an etiologic connection between tobacco use and cervical cancer, although some studies do indicate such a relationship. There are numerous potential explanations, including smoking as a behavior being associated with other behaviors that place women at increased risk of HPV infection. In a state like Kentucky, where the prevalence of smoking is so very high, one would expect that the disease burden from cervical cancer would also be high. A review of available data on invasive cervical cancer cases from the Kentucky Cancer Registry shows that this is indeed the case, with the incidence rate of invasive cervical cancer in Kentucky being as much as 40% higher than the SEER rate during the 1991-1998 time period. An analysis of available tobacco use history data from the KCR on women diagnosed with invasive cervical cancer during 1997-1998 shows that 61% of them indicated a history of tobacco use. PMID- 11787313 TI - The Kentucky Breast Cancer Task Force: a model for cancer management. PMID- 11787314 TI - In vitro quantitative evaluation of marginal microleakage in Class II restorations confected with a glass ionomer cement and two composite resins. AB - This study evaluated, in vitro, marginal microleakage in class II restorations confected with the glass ionomer cement Vitremer and with the composite resins Ariston pHc and P-60. The aims of the study were to assess the effect of thermocycling on those materials and to evaluate two methods utilized in the analysis of dye penetration. Sixty premolars divided in three groups were utilized; the teeth had proximal cavities whose cervical walls were located 1 mm below the cementoenamel junction. Half of the test specimens from each group underwent thermocycling; the other half remained in deionized water, at 37 degrees C. The specimens were immersed, for 24 hours, in a basic 0.5% fuchsin solution at 37 degrees C. For the analysis of microleakage, the specimens were sectioned in a mesio-distal direction, and the observation was carried out with the software Imagetools. The results were evaluated through the 2-way ANOVA and through the Tukey's test. All groups presented marginal microleakage. The smallest values were obtained with Vitremer, followed by those obtained with the composite resins P-60 and Ariston pHc. There was no statistically significant difference caused by thermocycling, and the method of maximum infiltration was the best for detecting the extension of microleakage. PMID- 11787316 TI - [In vitro study of marginal microleakage in dental caries treated with Er:YAG laser and restored with esthetic materials]. AB - The aim of this in vitro study was to evaluate marginal microleakage in class V preparations submitted to treatment with Er:YAG laser and restored with aesthetic materials. Sixty human molars were selected and class V cavities were prepared on the buccal and lingual aspects of their cervical thirds. The restorative technique followed the instructions of the manufacturers. The samples were divided in 3 groups of 20 teeth each: Group 1--control; Group 2--Er:YAG laser was applied on the enamel margin before the restoration was placed; Group 3--a thin layer of calcium hydroxide was applied on the axial wall before the restoration was placed. Each group was divided in 4 sub-groups and the teeth were restored with different aesthetic materials. All samples were submitted to thermocycling and stained with 50% silver nitrate. Based on the obtained results, we could conclude that there are statistically significant differences between the 12 experimental conditions tested. The samples which presented the greatest microleakage were those treated with Er:YAG laser and restored with light-cured glass ionomer cement, followed by those that received Er:YAG laser and the sandwich technique, the cavities restored with light-cured glass ionomer cement and those restored by means of the sandwich technique, in this order. PMID- 11787315 TI - [Morphologic evaluation of the bonding between adhesive/composite resin and dentin irradiated with Er:YAG and Nd:YAG lasers: comparative study using scanning microscopy]. AB - Since bonding systems were introduced in the restorative procedures carried out with esthetic materials, the treatment of dentin surfaces has been widely studied in order to establish the ideal technique. The application of 37% phosphoric acid on dentin is still the best known method. However, alternative methods for treating the dentin surface have been discussed in the literature, including the utilization of some kinds of laser irradiation. The purpose of this research was to morphologically evaluate the bond between adhesive materials and the dentin treated with Er:YAG and Nd:YAG lasers, in a comparative study by means of scanning electron microscopy (SEM). Irradiation either substituted acid etching, or was associated to it. Recently extracted bovine incisors were utilized. They received class V cavity preparations and were restored with a bonding system and a light-cured composite resin. Meanwhile, some of the teeth underwent irradiation with Er:YAG laser or Nd:YAG laser before the application of the bonding agent and the composite resin. The samples were selected, prepared for SEM and submitted to morphological analysis. Data were registered in photomicrographs. Based on the microscopic observations, we concluded that only in the dentin surfaces submitted to irradiation with Er:YAG laser and to acid conditioning there was penetration of resin into the dentine. With the Nd:YAG laser treatment, there was only visual superposition of resin over the dentin surface, which suggests that there was only occlusion of the tubules, with characteristics of fusion in the superficial dentine. PMID- 11787317 TI - Plaque removal by manual and electric toothbrushing among children. AB - The purpose of this study was to compare the effectiveness of plaque control performed with electric and manual toothbrushes. Fifteen children with primary dentition and 14 children with mixed dentition were divided in two groups and randomly assigned to utilize a manual or an electric toothbrush. In the first session, professional plaque removal was performed, and the children spent 24 hours without brushing their teeth. In the second session, plaque was disclosed and assessed on all facial and lingual surfaces. After that, all children brushed their teeth with the predetermined toothbrush. The next procedure was the disclosure and measurement of residual plaque. After a period of 7 days, the children switched the kind of toothbrush, and the same procedures were repeated. According to the statistical analysis of the results, there were no significant differences concerning plaque removal when the toothbrushes were utilized by children with mixed dentition. On the other hand, the electric toothbrush promoted significantly greater plaque removal on the lingual surfaces of teeth from children with primary dentition. PMID- 11787319 TI - Odontogenic tumors: analysis of 127 cases. AB - One hundred and twenty-seven cases of histologically confirmed odontogenic tumors were retrieved from a total of 5,289 oral and maxillary lesions diagnosed at the Division of Oral Pathology, Federal University of Rio Grande do Norte, during a period of 30 years (1970-1999). The most common histological diagnosis was odontoma (50.40%), followed by ameloblastoma (30.70%). The prevalence of odontogenic tumors was greater in females and the peak incidence occurred in the second and third decades of life. The main anatomical location was the mandible, and no malignant tumors were found. PMID- 11787318 TI - [Prevalence of oral changes in children attending public pediatric dental clinics in Ponta Grossa, PR, Brazil]. AB - This investigation was carried out in order to determine the prevalence of oral alterations among 200 infants aged 0 to 24 months (108 males and 92 females), who were seen at public pediatric dental clinics from Ponta Grossa--PR, Brazil. The infants were examined during routine appointments. The data were analyzed and the results revealed that 21.00% of the children had oral conditions, which were more frequent among children aged 0 to 3 months (26.98%). The most prevalent condition was the inclusion cyst (35.71%), followed by benign migratory glossitis (23.81%) and candidiasis (11.90%). The prevalence of inclusion cysts was higher among females (10.87%), and the benign migratory glossitis was more frequently seen in males (6.48%). No tumors were found. With regard to the management of the conditions, it was noticed that no treatment was required in 76.19% of the cases. These findings are in agreement with those reported in the literature, and it was concluded that most of the oral conditions in infants are benign and do not require any treatment. In spite of that, health professionals (dentists and pediatricians) must be aware of those alterations in order to tranquilize the children's parents and to detect the need for any intervention. PMID- 11787320 TI - [Evaluation of 3 methods of DNA extraction from paraffin-embedded material for the amplification of genomic DNA using PCR]. AB - There are several protocols reported in the literature for the extraction of genomic DNA from formalin-fixed paraffin-embedded samples. Genomic DNA is utilized in molecular analyses, including PCR. This study compares three different methods for the extraction of genomic DNA from formalin-fixed paraffin embedded (inflammatory fibrous hyperplasia) and non-formalin-fixed (normal oral mucosa) samples: phenol with enzymatic digestion, and silica with and without enzymatic digestion. The amplification of DNA by means of the PCR technique was carried out with primers for the exon 7 of human keratin type 14. Amplicons were analyzed by means of electrophoresis in an 8% polyacrylamide gel with 5% glycerol, followed by silver-staining visualization. The phenol/enzymatic digestion and the silica/enzymatic digestion methods provided amplicons from both tissue samples. The method described is a potential aid in the establishment of the histopathologic diagnosis and in retrospective studies with archival paraffin embedded samples. PMID- 11787321 TI - [Clinical and comparative study of the image quality of 3 digital radiographic systems, E-speed film and digitalized film]]. AB - The aim of this study was to evaluate, subjectively, the image quality of two CCD digital systems, a digital storage phosphor system, a digitized film and an E speed film. Five objects were radiographed with 50, 60 and 70 kVp, with exposure times of 0.08, 0.13, 0.2, 0.4 and 0.8 s. In order to maximize the fidelity of the results, the dental X-ray unit employed was submitted to an evaluation so that the relation between exposure time and dose could be established. A good reproducibility was obtained. Six evaluators analyzed 375 images, using a scoring scale which ranged from 0 to 4. The results revealed different responses, indicating that the storage phosphor system had the best performance, in the various exposures employed. However, it was possible to conclude that all systems studied, except for the Sens-A-Ray, can offer images in ideal conditions for the diagnosis, as long as their latitudes are respected. PMID- 11787322 TI - [Influence of different methods of chemical disinfection on the physical properties of type IV and V gypsum dies]. AB - Several instruments and materials frequently used in prosthodontics--such as stone casts, dental impressions, interocclusal records--are classified, by the dental literature, as vehicles of transmission of infectious diseases to those who handle them. The present study aims at comparing dimensional alteration, superficial texture and compression resistance of stone dies submitted to different disinfection methods: 30-minute immersion in 1% sodium hypochlorite or in 2.2% alkaline glutaraldehyde (with or without previous ultrasonic washing) and addition of 2.2% alkaline glutaraldehyde or 5% sodium hypochlorite to the gypsum during its preparation. It was possible to conclude that: (1) chemical disinfection did not cause significant dimensional alteration in stone dies; (2) superficial texture was altered according to the disinfection method utilized; (3) immersion in disinfectant solution during 30 min, as well as the addition of disinfectant to the gypsum during its preparation, reduced the compression resistance of dies. PMID- 11787323 TI - [Dimensional changes of silver and gallium-based alloy]. AB - Gallium-based dental alloys were created with the aim of solving the problem of toxicity of mercury. The material shows mechanical properties similar to those of dental amalgam, but researches point out two unfavorable characteristics: great corrosion and excessive post-setting expansion, and the latter is capable of cracking dental structures. The aim of this study was to evaluate, during 7 days, the in vitro dimensional alteration of a gallium dental alloy (Galloy, SDI, Australia), in comparison with a dental amalgam containing zinc (F400, SDI, Australia), as a function of the contact with saline solution (0.9% NaCl) during the setting period. The storage experimental conditions were: storage in dry environment, immersion in saline solution and contamination during condensation. Additionally, the effects of contamination during the trituration of dental amalgam and the effects of protecting the surface of the gallium alloy with a fluid resin were studied. Specimens were stored at 37 degrees C +/- 1 degree C, and measuring was carried out, sequentially, every 24 h during 7 days. When the gallium alloy was either contaminated or immersed, an expansion significantly greater than that observed in the other experimental conditions was noticed after 7 days. The application of a fluid resin to protect the surface of the cylinders was able to avoid the increase in expansion caused by superficial moisture. The amalgam alloy did not show significant dimensional alterations, except when it was contaminated during trituration. PMID- 11787324 TI - [Quantitative evaluation of Streptococcus mutans and Candida species and salivary factors in the oral cavity of patient undergoing radiotherapy]. AB - The aim of this study was to quantify the microorganisms Streptococcus mutans and Candida sp in the oral cavity of patients with oropharynx carcinoma, before, during and after radiotherapy, and to correlate the results with salivary factors such as pH, buffer capacity (CT) and flow rate (FS). Saliva samples were collected, diluted and inoculated in SB-20 agar and in Sabouraud agar, for Streptococcus mutans and Candida sp, respectively. Previously to dilution, the concentrated saliva was analyzed, and the salivary factors were determined. After the growth of colonies, the number of microorganisms was determined in CFU/ml. The analysis of the results allowed to conclude that the salivary factors are related to the presence of microorganisms, and that the number of CFU/ml increased as salivary flow rate decreased. The effects of radiation compromised salivary homeostasis and favored the increase of infection by yeasts and bacteria. PMID- 11787325 TI - [Behavioral eating disorders and their effects on the oral health in adolescence]. AB - Anorexia nervosa and bulimia nervosa are serious eating disorders that affect a significant number of adolescents and young adults. Individuals with anorexia nervosa tend to ignore or deny their excessive dieting and may present purging habits. The individual with bulimia nervosa spends great effort and time in compensating the effects of binge eating with dieting and fasting, self-inducing vomiting, utilization of laxatives or overexercising. The incidence of those behavioral disorders seems to be increasing, but there are no epidemiological data on that matter in Brazil. The dental practitioner has an important role in identifying these disorders since toothwear is very frequent due to the acidic oral environment caused by vomiting. The dentist can help to minimize the effects of anorexia and bulimia on the dentition. The objective of this study is to review the features of those behavioral eating disorders and to highlight the importance of being prepared to diagnose them and implement a comprehensive treatment of patients. PMID- 11787326 TI - [Mechanisms of hypoxemia in COPD]. PMID- 11787327 TI - [Nocturnal hypoxemia in COPD and its treatment]. PMID- 11787328 TI - [Comparative changes in PaO2 in moderately hypoxemic COPD patients treated with almitrine versus placebo for one year]. PMID- 11787329 TI - [Current indications of long-term oxygen therapy in patients with COPD]. PMID- 11787330 TI - [Therapeutic indications targeting etiology of progressive multiple sclerosis]. AB - The indication for a long-term treatment in secondary or primary progressive multiple sclerosis is raised in more than half of the patients with MS. The fact that the pathogenic mechanisms involved in these two entities are unknown makes it difficult to predict the clinical course. The still insufficient knowledge of the MRI parameters is another obstacle to overcome. Nevertheless, the results of a certain number of clinical trials have, despite the methodological inadequacies, provided some insight. Immunomodulators, such as interferon-beta, have shown some efficacy, particularly in patients with a still inflammatory form of secondary progressive MS. Massive short-term immunosuppression does not appear to affect the course of progression but prolonged immunosuppression appears to be able to retard progression, at least in certain patients. This points out the importance of starting treatment as early as possible, before the development of irreversible damage. A better analysis of results already published, and most importantly, of results currently under way, should be most helpful in terms of therapeutic management if not in terms of our understanding of the pathophysiological processes involved. PMID- 11787331 TI - [Treatment of progressive forms of multiple sclerosis]. AB - There is not a standardized definition of rapidly worsening Multiple Sclerosis (MS). Arbitrary, we have designed under this term patients having a very active MS (patients having more than 2 relapses within the last 12 months) or rapid progression of handicap (more than 2 points EDSS progression within the last 12 months). The design of most previous studies using azathioprine, cyclophosphamide, methotrexate do not fulfill criteria to draw final conclusions as to the efficacy of these drugs as an immunoprophylactic agent in Multiple Sclerosis (MS). During the last five years, efficacy of immunomodulatory and immunosuppressive agents was provided by some well-designed randomized control clinical trials: among the immunosuppressors, mitoxantrone deserves special consideration as there were three controlled trials in Europe during the two last years that demonstrated strong efficacy both on clinical and MRI criteria. Due to its potentially cardiotoxicity, related to total cumulative dose, mitoxantrone should presently only be used in selected patients with a very high relapse rate and incomplete remission or in those who do not respond to INF beta treatment. The immunomodulatory agents (interferon beta 1a or 1b, copolymer 1) demonstrated a significant effect on the reduction of relapse rate (about 30 p. cent reduction), on progression of handicap and on MRI. In secondary progressive MS, an effect on progression is demonstrated only on patients still having relapses. No trial devoted to worsening patients as defined above have been yet designed with immunomodulatory agents. PMID- 11787332 TI - [Therapeutic indications targeting etiology. (With the exception of primary progressive forms)]. AB - On the subject of the treatment of Multiple Sclerosis, JM Charcot stated in 1877 that "the time has not yet come when such a subject can be seriously considered". Fortunately such point of view is no more up to date. This chapter will review the available treatment for relapsing-remitting and secondary progressive Multiple Sclerosis. The immunosuppressive drugs and steroids have been used for many years. Immunomodulation appeared more recently. A review of the evidence on the use of those drugs will be performed. PMID- 11787333 TI - [Locomotor reeducation and multiple sclerosis. A critical analysis of the literature]. AB - Multiple Sclerosis (MS) is a disabling chronic neurological disorder with multiple motor impairments and its progressive course leads to severe disability. The question of the value of exercises program and physiotherapy to reduce these motor disorders and their consequences was raised. This literature overview is based on data from common database: Medline, Embase, Cochrane Library. Were selected articles corresponding to open studies and especially clinical controlled randomised trials. To be analysed, each article should correspond with inclusion criteria: confirmed diagnosis according to Poser's criteria, secondary or primary progressive form of MS without relapse for the study period, randomisation according to severity assessed by the Expanded Disability Status Scale (EDSS), no change in symptomatic drugs along the study period, and a simple blind assessor. Impairment, disabilities, handicap and quality of life had to be measured. Five clinical controlled randomised trials were consistent with these criteria. They demonstrated the effectiveness of comprehensive programs on motor function in the less severe forms of MS, but also their inability to change the course of the most severely affected forms. However, the effects on disability, handicap and quality of life were significant in comparison with control patients. These trials emphasised the value of multidisciplinary programs including physiotherapy and occupational therapy, carried out daily or 3 times a week by specialised staffs. The effects lasted only few weeks or months, requiring to propose them again after this period. Other controlled randomised studies also stressed the value of specific programs: temporary alleviation of spasticity and fatigue with cooling techniques; aerobic endurance training for less severely affected patients to prevent disuse consequences and improve fitness and quality of life; expiratory training to enhance coughing capacity and prevent pulmonary infections in very disabled patients. From this overview study, it seems that multidisciplinary comprehensive programs clearly provide benefits to those patients and contribute to reduce disability and improve quality of life at each stage of MS. PMID- 11787334 TI - [Spasticity and multiple sclerosis]. AB - Spasticity is a common symptom in MS patients. It is easy to recognize and evaluate spasticity at rest. The efficacy of numerous treatments has been well documented. Nevertheless, it is difficult, particularly in MS patients, to assess the functional disability due to spasticity and the functional benefit due to treatment. This is why it is appears more appropriate to use therapeutic tests with transitory effects such as anesthetic blocks in case of focal spasticity or intrathetical baclofen in case of diffuse spasticity. It is also possible to use reversible treatments such as botulinum toxin injections before proposing section of a peripheral nerve. PMID- 11787335 TI - [Therapeutic indications in spasticity symptoms of multiple sclerosis]. AB - Spasticity is reported in 90 p. 100 of multiple sclerosis patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. Review of comparative efficacy and tolerability of anti-spastic agents is performed in order to guide rational prescribing. PMID- 11787336 TI - [Genital and sphincter disorders]. AB - Symptomatic bladder dysfunction occurs at some time in most patients with multiple sclerosis. Detrusor hypereflexia and sphincter dyssynergia are the main dysfunctions. Anticholinergic medication is currently the most effective and the most common treatment of overactive bladder with reduced bladder capacity and uninhibited detrusor contractions. Desmopressin, surgery, permanent indwelling catheter or external device are used in some cases. Nevertheless essential to bladder management is understanding to what extent the patient has incomplete emptying while complaining predominantly of symptoms of detrusor overactivity: frequency and urgency, with or without urge incontinence. Intravesical capsaicin and botulinum toxin injected into the detrusor seems promising means of treating intractable bladder hyperreflexia. If the post-micturition residual volume is raised, intermittent self-catheterization is the most adequate method to achieve bladder emptying of patients with MS. Physical and cognitive disability as well as patients motivation can reduce their ability to perform catheterization. In such situation, alphablockers show moderate efficacy and botulinum toxin urethral sphincter injection or surgical solution may be discussed. Disturbed anorectal physiology is common in MS, but there are as yet few specific treatments. The efficacy of oral sildenafil for treatment of neurogenic erectile failure increases the range of treatment available for men with sexual dysfunction. In women, mechanical remedies, treatment of motor and sensory loss are effective for dyspareunia. Patients of both sexes are likely to welcome to discuss their problem, and counselling or psychotherapy may be of use. PMID- 11787337 TI - [Therapeutic indications in symptoms of bladder and sphincter disorders in multiple sclerosis]. AB - Bladder and bowel dysfunction is common in multiple sclerosis. After accurate diagnosis of dysfunction, a management program with anticholinergic or alphabloquers drugs is mandatory. Intermittent catheterization, surgical treatment, or electrostimulation are proposed in most severe cases. Therapies for intestinal disorders are more limited. Management of symptoms and different therapies are reviewed. PMID- 11787338 TI - [Therapeutic indications for managing symptoms: fatigue]. AB - Fatigue is a common complaint in patients affected by multiple sclerosis. Its mechanisms are poorly understood and are likely diverse. The term "fatigue" has been used for asthenia at rest but also for fatigability during exercise. Amantadine is the only drug that has a proven therapeutic benefit in randomized, double blind, controlled trials. Inhibitors of serotonin re-uptake are used pragmatically because of the relationship between fatigue and depression. Aminopyridins may improve fatigability, mainly at the level of lower limbs. PMID- 11787339 TI - [Pain in multiple sclerosis]. AB - Pain is a major issue in the care of Multiple Sclerosis patients. It is present in more than half of the cases and it adopts many aspects, which frequently ruin the patients quality of life. Most of them do not receive appropriate treatments, as clinicians are more oriented towards controlling the immuno-pathogenic process of the disease than coping with symptomatic consequences of the lesions. Any clinical form of the disease may include pain and no clinical criteria have been correlated with the occurrence of pain: neither age, nor gender, nor MS subtypes nor severity of the handicap; almost all MS cases will complain of pain at a time or another of their evolution. A key issue is to make a precise diagnosis of the type or types of pain that any patient reports: is pain due to a central neuropathic or a nociceptive pathogenesis. Treatments will depend upon these two main pain mechanisms and will use different agents according to each type: antispastic, antiepileptic, anti-inflammatory, opioids.... Pain has to be taken in consideration in every MS patient and adapted treatment strategy must be prescribed. PMID- 11787340 TI - [Tremor and abnormal movement in multiple sclerosis: symptomatic therapeutic indications]. AB - Tremor and movement disorders in multiple sclerosis (MS) patients cause a severe functional impairment. The different types of tremor observed in MS are: cerebellor tremor with a dominant intention component, Holmes tremor characterized by the addition of rest and postural components and palatal tremor. When no medication can improve the functional status, it is acceptable to discuss the deep brain stimulation in the VIM thalamus, thus making possible a partial attenuation of the rest and postural component, mainly affecting the proximal part of the affected limb. Among the movement disorders, paroxysmal dyskinesias are not rare and a good therapeutic response is obtained with carbamazepine: dystonia and parkinsonism are usually coincidental features during MS. PMID- 11787341 TI - [Therapeutic indications in symptomatic cognitive and psychopathological disorders in multiple sclerosis]. AB - Cognitive impairment and psychiatric disorders occur in about 60 p. cent of multiple sclerosis patients. In general, impairment develops in established cases, although it can present early in the disease course. The pattern of neuropsychological deficits is characterized by deficits in attention, memory and executive functions; No specific treatment seems to be effective in cognitive impairment but appropriate strategies could limit the negative impact on this disease. Depressive states are twice frequent and usual antidepressant drugs seems to demonstrate some efficacy. PMID- 11787342 TI - [Therapeutic indications of symptomatology: fatigue, pain, abnormal movements and reeducation]. AB - Multiple Sclerosis is a chronic progressive and handicapping pathology of the central nervous system. Despite the recent progress no curative molecule has fundamentally modified its prognosis. Within this context symptomatic treatments are inevitable. As part of this consensus conference we have made a systematic critical and objective review about the literature relating how to take care symptomatically of "fatigue", pain, movement disorders and rehabilitation. PMID- 11787343 TI - [Clinical evaluation of follow-up and disease course]. AB - The clinical assessment of the evolution of Multiple Sclerosis (MS) is based on international criteria. For the definition of relapse and progression, the so called Schumacher criteria (1965) may be chosen. For the definition of clinical subtypes (relapsing-remitting, secondary progressive, primary progressive, and progressive-relapsing), the criteria issued from a survey conducted by the group of Lublin (1996) are mandatory. One may be cautious to apply such research-driven sets of criteria to clinical practice. Many scales have been elaborated for the evaluation of the handicap caused by MS (i.e. neurological deficit, impairment, and "handicap"). None is perfect, but the Expanded Disability Status Scale (EDSS, Kurtzke, 1983) is widely used. Recent development in the elaboration process of scales ("scalology") may soon lead to the validation of new composite outcome measures. PMID- 11787344 TI - [Value of MRI in patients with multiple sclerosis]. AB - Diagnosis criteria of multiple sclerosis (MS) have been recently reconsidered, introducing the possibility to validate temporal dissemination with the use of MRI. In fact, MRI parameters may be considered as reflecting the biological activity of MS. MRI is used to monitor treatment in clinical trials. However, and except for particular circumstances, its use in routine follow-up of patients with MS is not recommended, because of weak correlations with clinical disability and technical difficulties of such follow-up. PMID- 11787345 TI - [Neuropsychological evaluation and psychopathology of multiple sclerosis]. AB - Cognitive and psychiatric disorders have long been described in MS. However, these symptoms were only well evaluated starting about fifteen years ago. More recently, there has been renewed interest in cognitive and psychiatric assessment in MS, especially due to the emergence of new therapies for the disease. Psychiatric symptoms mainly include depression and anxiety. Depression is generally moderate, but there is a risk of suicide that is clearly higher than in the general population. Depression is not correlated with the duration of symptoms, type of disease or level of disability. Mild elation and pathological laughing and crying can be associated and are more frequent in case of severe disease. Bipolar affective disorders and alexithymia are more rare. The question of premorbid personality has been questioned for depression but not confirmed. It has been suspected for bipolar affective disorders. Cognitive disorders are observed in 40 to 65% of the cases at any period of the disease. They mainly include an impairment of working and long-term memory, executive functions and attention whereas global intellectual efficiency is impaired later. While cognitive disorders can be observed early in the course of the disease, there is no correlation with the level of disability or duration of the disease. Progressive MS and especially secondary progressive then primary progressive forms are more subject to cognitive deficits than relapsing remitting MS. For a similar cognitive impairment, progression could be a negative factor for the disease course. Cognitive and psychiatric assessment of patients can be discussed on the basis of why, how and when. Psychiatric assessment is not particularly difficult when there are psychiatric complaints, but cognitive assessment should be explained to the patients and justified when there is no complaint. However, detection of cognitive deficits would lead to better patient management. Psychiatric assessment will mainly use controlled or open interviews and assessment scales to evaluate the level of depression and/or anxiety. For cognitive assessment, short-term batteries focusing on the main dysfunctions are recommended. Psychometric evaluation should not be performed during a period of relapse, hospitalization or immediately after starting drug therapy for depression or anxiety. The cognitive evaluation should be explained to the patient and should include a parallel assessment by a psychologist well trained in MS. The evaluations will be adapted to the situation and the goals. Early interviews evaluate the psychopathological profile that can then be reevaluated during each consultation. Cognitive assessment is mainly proposed in case of interferon therapy, spontaneous complaints of the patient or abnormal difficulties in daily life or occupational activities. In all cases, patient management requires a multidisciplinary approach. PMID- 11787346 TI - [Rehabilitation management in neurologic follow-up of the multiple sclerosis patient]. AB - New immunomodulatory treatments of Multiple Sclerosis lead to considerable changes in the doctor-patient relationship. Today the neurologist must become involved in comprehensive management of MS patients. He/She must become familiar with the specific methodology of assessment in rehabilitation, and especially with the measurement of disability. Some specific measures have been developed in this field, i.g. the Functional Independence Measure (FIM). Although no significant change was demonstrable on neurological status decline as measured by EDSS in progressive phase, several recent controlled studies have demonstrated the efficacy of inpatient or outpatient rehabilitation programs, when assessment was based on disability, handicap and quality of life measurement. We emphasized the neurologist's role in determining adequate timing for rehabilitation according to the course of disease and therapeutic choices, but also in the setting of patient-centered functional goals for rehabilitation program. PMID- 11787347 TI - [Quality of life in multiple sclerosis]. AB - The insensitivity of the clinical scales usually performed in MS patients led to measure the quality of life (QoL). QoL includes several important domains of health which are regarded by patients as being more important determinants of their overall health states. Some aspects of QoL of MS patients (early collapse in the disease, impact of interferons therapy) suggested that its measurement is relevant in assessing the effect of treatment and progression of the disease. PMID- 11787348 TI - [Evaluation of follow-up and evolution of multiple sclerosis]. AB - The aim of this paper is to review the quantitative methods used for assessing neurological status in multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) is the most wide used. Its psychometric properties, validity, and inter- and intra-rater reliability are modest and responsiveness is weak. Similar results are obtained with the other scales used. The recently developed Multiple Sclerosis Functional Composite (MSFC) scale for clinical trials satisfies this requirement, but is not suitable for individual evaluation. There is no scale in French for assessment of cognitive disturbances and only one, the SEP-90, for quality of life. Brain and spinal cord abnormalities with conventional magnetic resonance imaging parameters (T1, T2-weighted and gadolinium enhanced images) have a weak relationship with disability. New magnetic resonance techniques (magnetic resonance spectroscopy and magnetized transfer imaging) would be more sensitive and should be further investigated. PMID- 11787349 TI - [Imparting the diagnosis and educating patients with multiple sclerosis]. AB - The neurologist must include the diagnosis announcement process in the comprehensive care of the MS patient. This process is standardized and adapted to the needs of each patient. It must integrate the pattern of psychological reactions following negative events and the adaptive strategies to a chronic disease. The announcement of the diagnosis, given by the neurologist, consists in technical information and emotional support, during a programmed discussion, at the adequate moment. The information must respond to the patient's needs, be easily understandable and given step by step according to the period of the disease. The neurologist is usually the first source of medical information followed by the MS societies and internet. PMID- 11787350 TI - [Daily life activities and multiple sclerosis]. AB - The onset of Multiple Sclerosis usually concerns young adults who are making plans for their life. The personal, familial, professional plans must be adapted to the course of the disease. This adapted daily life must be as normal as possible to prevent the social loneliness which is the principal complication of Multiple Sclerosis. Three frequent situations of daily life have recently been studied in Multiple Sclerosis. Pregnancy is permitted. There is a dramatic decrease of the relapse rate during pregnancy but an obvious increase after delivery. Pregnancy has no influence on disability. Vaccinations do not favor the onset or the worsening of Multiple Sclerosis according to studies with large number of patients (in particular hepatitis B vaccination). Stress is not able to trigger the onset or relapses of Multiple Sclerosis. Stress could even protect against relapses. The Multiple Sclerosis daily life does not need to take specific precautions which would expose to the marginalization of patients. PMID- 11787351 TI - [Medical-social aspects of multiple sclerosis]. AB - On a daily basis the quality of life of patients suffering from multiple sclerosis (MS) partially depends on social measures. These are not specific to MS. Patients often need to be helped by hospital or town social services for the numerous and complicated administrative steps to be taken. The information given to a patient is of prime importance concerning his rights, particularly his occupational rights. Many organisations have to be contacted to obtain financial and material aids, even if the latter are considered insufficient in many fields especially for improvements in accommodation. An invalidity card may entitle its holder to certain tax reductions. The competences of the COTOREP are wide-ranging and include the recognition of the handicapped worker, his training and his regarding at work, his orientation and admission into a specialised structure, the degree of his invalidity rate and should his handicap justify it, benefits such as the handicapped adults allowance and the compensatory third person's allowance. It is essential to adopt a multidisciplinary way when dealing with MS in order to provide a better care, experiments in specialised structures and networks are being undertaken. Numerous partners are taking part in these new approaches and patient associations may find their place there. Social aspects have to be taken into account as well in the way the cost of the disease is evaluated in terms of money and humanity. PMID- 11787352 TI - [Multiple sclerosis: cost of the illness]. AB - Economic assessments for multiple sclerosis (MS) first appeared in the nineties. Drug costs were initially marginal before the recent introduction of interferon beta. To evaluate the burden of MS, economic studies were carried out in addition to specific cost-of-illness studies. Like other chronic illnesses, MS patients can have mild to moderate or severe disabilities. This led to the need for indirect cost analysis. We interrogated the Medline database from 1985 to 2001 to select cost-of-illness studies. We present our findings here by type of methodology used, health care system and level of disability. We found that indirect costs are related to patient age at symptom onset (20-40 years). In most counties, excepting the United Kingdom, hospital costs dominate direct costs. Finally, MS costs are related to the stage of the disease. PMID- 11787353 TI - [Illness management modalities]. AB - Multiple sclerosis (MS) is the most common neurological disease disabling young adults. Patients with MS experience symptoms in an unpredictable pattern over years or decades. The doctor/patient relationship in MS, beginning with the announcement of the diagnosis has to grow stronger with a clear structured information following from the many available studies of the medical literature. This is all the more welcome since the introduction of a new generation of disease-modifying agents which has a radical effect on the management of the condition. This management of MS must also concentrate on symptom relief, palliative care and complementary therapies including rehabilitation when a disability occurs. Nowadays, a quality health service for people with MS need to be intimately involved in the long-term care of a disease which has frequently a social and occupational impact. Physicians of several disciplines, primary medical care, social service and nurses should work as an integrated medical network model focusing on the patient and his family. PMID- 11787354 TI - [Consensus Conference on Multiple Sclerosis, Paris, 7 and 8 June 2001. Organized by the French Federation of Neurology with participation of l'ANAES. Recommendations of the Jury]. PMID- 11787355 TI - [Diagnostic criteria of different clinical forms ]. AB - Multiple sclerosis (MS) is a disease of unknown origin and for which there is no specific diagnostic test. The diagnosis of MS is always the result of a more or less simple procedure, depending on the cases, and it remains uncertain until evidence of anatomo-pathological signs have been brought forward. An almost unanimous consensus does exist regarding several points. In the presence of suggestive or, at least, compatible neurological signs and in the absence of any alternative diagnosis according to a neurologist expert in MS, the diagnosis of MS is based on three criteria: the evidence of at least two different lesions in the white matter of the central nervous system, which is called the "space dissemination" criterion; the evidence of at least two different episodes in the disease course, which is called "time dissemination"; the evidence of a chronic inflammation of the central nervous system revealed through the analysis of the cerebrospinal fluid, i.e. the "infammatory" criterion. The observation of one or several of these criteria allows to establish the diagnosis of MS with more or less certainly, likely to be reassessed according to the subsequent course of the disease. There is a wide consensus today with Poser's classification (Poser et al., 1983) which combines the three criteria and distinguishes five different categories. According to Poser et al., space dissemination may be proved on clinical examination, but also with the brain MRI and, failing that, with the evoked potentials. Time dissemination is based only on clinical signs and the inflammatory criterion is as significant as the two other criteria. This classification has just been revised by an expert committee (McDonald et al., 2001) who wish to simplify it into two different categories (MS vs possible MS). It has been suggested that time dissemination should be proven by the observation of MRI signs three months at least after the previous clinical episode or the previous MRI. It has been suggested also to use the inflammatory criterion in second position in replacement of the space criterion when the latter is missing on the clinical and paraclinical levels. Time will say whether this new classification will replace the previous one. PMID- 11787356 TI - [Diagnostic criteria of multiple sclerosis with reference to different clinical forms]. AB - This paper reviews the validity of clinical diagnostic criteria and clinical course classification. Validation based on the pathological verification is not available. MS diagnosis remains clinical based on the objective demonstration of dissemination of lesions suggestive of MS in both time and space. Also clinical features are not specific and sensitive enough. MRI is primordial. MRI diagnosis criteria are discussed. Clinical course classification is difficult in regard to the extreme heterogeneity of the disease. Classical distinction between recurrent and progressive forms is reviewed from natural history studies and recent MRI and pathological findings. Recent studies focus on presentation including monosymptomatic disease and primary progressive forms. PMID- 11787357 TI - [Borderline forms of multiple sclerosis]. AB - Multiple sclerosis (MS) has been described for more than a century, but its cause remains unknown and no simple diagnostic marker is available. Therefore, it is not surprising that numerous articles were written on closely related diseases, borderline forms of multiple sclerosis. Different forms have been distinguished: a clinical form of MS (Devic's neuromyelitis optica), pathological forms (Balo, Schilder, Maburg), forms associated with MS (peripheral neuropathy, autoantibodies) and closely related disorders (acute disseminated encephalomyelitis). PMID- 11787358 TI - [Diagnostic criteria of borderline forms of multiple sclerosis]. AB - Border forms of multiple sclerosis (MS) can be separated in two groups: either they are variants of MS or they are distinct from MS but they share several characteristics with MS thus representing for some of them a continuum with MS. All these entities are central nervous system demyelinating diseases. Here we describe, for the first group, MS in childhood, MS in elderly subjects, Balo's concentric sclerosis, Schilder's myelinoclastic diffuse sclerosis and MS simulating a mass lesion, and for the second group, acute disseminated encephalomyelitis and Devic's neuromyelitis optica. PMID- 11787359 TI - [Diagnostic criteria of multiple sclerosis in neuroimaging]. AB - Although sensitivity of MRI to MS is high, its specificity is limited and requires the use of criteria such as Paty's, Fazekas's and then Barkhof's, taking successively into account the technical progress and the use of contrast agents. In the later the confidence level brought by contrast enhancement is equivalent to that of 9 hyperintense lesions seen on T2-weighted imaging. Therefore MRI is now the first paraclinical test to perform for MS suspicion and is aimed at the diagnosis MS from the first clinical event, without need to wait for the second relapse for temporal dissemination confirmation. The goal is to be able to discuss early treatment if it becomes clear that it could prevent disease progression. The early evidence of spatial and temporal dissemination of the disease takes equally into account the clinical and MRI information and eliminates the previous terminology of "clinically defined MS". Presently the diagnosis is either confirmed or ruled out and in a limited number of cases or before the completion of the work up phase the category of "possible MS" is used. Although progress were also made in the field of prognosis evaluation of MS with MRI, it still brings less definitive information to predict individually the evolution of each form of the disease. This opens a large place for new techniques such as magnetisation transfer, spectroscopy and diffusion imaging which are already able to help pathophysiological understanding and which may play an increased role even at the individual level in the future. PMID- 11787360 TI - [Diagnostic criteria of multiple sclerosis in neuroimaging]. AB - To date, there is no biological test available with enough confidence to make alone a diagnosis of Multiple Sclerosis (MS). MS diagnosis criteria are then an association of clinical and para clinical criteria that allow an objective demonstration of dissemination of lesions in both time and space. Adapted MRI criteria from Barkhof have a good sensitivity and the best specificity to evaluate MS. 3 of 4 criteria are necessary: 1 gadolinium enhancing lesion or 9 T2 hyper intense lesions; at least 1 infratentorial lesion; at least 1 juxtacortical lesion; at least four periventricular lesions; NB: 1 spinal cord lesion can substitute for 1 brain lesion. News methods as spectroscopy, magnetization transfer, diffusion MRI and functional MRI complete results of conventional MRI and give new informations about physiopathology of MS demyelinating lesions. PMID- 11787361 TI - [Contribution of biology to diagnosis of multiple sclerosis]. AB - The analysis of the cerebrospinal fluid is the only biological test included in the diagnostic criteria for MS. A search for intrathecal IgG synthesis by isoelectrofocussing should always be performed when the cerebrospinal fluid is analyzed for a possible diagnosis of MS. Intrathecal IgG synthesis is detected in about 95 p. 100 of MS cases. However, it is not specific for MS and only signs the inflammatory nature of the nervous system lesions. In our opinion, analysis of the CSF should be proposed systematically for primary progressive MS, in most cases of monosymptomatic demyelinating syndromes, and according to the clinical context and the result of the MRI analyses in the remaining forms. To date, no prognostic criteria can be drawn from the analysis of the CSF. Other biological tests can be performed in order to eliminate other diagnosis. These tests only have a great interest in atypical forms of the disease. PMID- 11787362 TI - [Biological diagnostic criteria in multiple sclerosis]. AB - The clinical diagnosis of multiple sclerosis (MS) can be supported by the analysis of the cerebrospinal fluid (CSF) by the detection of an inflammatory reaction in central nervous system. The most sensitive method for the detection of oligoclonal IgG bands is isoelectric focusing. However magnetic resonance imaging (MRI) is more sensitive and predictive. Nevertheless CSF study is useful in monosymptomatic manifestation when MRI is normal, and primordial in primary progressive MS diagnosis. More studies are needed to determine the optimal sequence of CSF study, MRI and evoked potentials in the diagnosis of different presentation of MS. PMID- 11787363 TI - [Diagnostic criteria of multiple sclerosis: electrophysiological criteria]. AB - We have made a review on the use of evoked potentials in multiple sclerosis (MS) for the past 30 years, in the diagnosis of MS, to disclose subclinical lesions or to assess atypical symptoms. Yet the role of evoked potentials in evaluation of multiple sclerosis has been changed since MRI is now widely and easily used for the diagnosis of MS. Evoked potentials are useful when symptoms are atypical without any objective impairment and when symptoms have already recovered at the time of clinical examination. Visual evoked potentials and somatosensory evoked potentials are widely used thanks to their diagnostic value and their ability to disclose spatial dissemination of multiple sclerosis. Evoked potentials have to be recorded in validated technical conditions such as to ensure reliability of data and have to be interpreted in reference to a population of healthy people recorded in the same conditions and in the same age range as MS patients. PMID- 11787364 TI - [Electrophysiological diagnostic criteria of multiple sclerosis]. AB - Visual and somatosensory evoked potentials are useful to identify patients at increased risk for developing Multiple sclerosis (MS). However Magnetic Resonance Imaging (MRI) is more sensitive and predictive. More studies are needed to determine the optimal sequence of evoked potentials and MRI that best predict the development of MS especially in monosymptomatic manifestations and in primary progressive MS. PMID- 11787365 TI - [Therapeutic indications for acute episodes of multiple sclerosis]. AB - The natural history of multiple sclerosis (MS) exacerbations is characterized by a poor outcome in about 70 p. cent of cases. By contrast, the outcome of a first episode of acute optic neuritis (ON) is usually good. However the disability associated with MS bouts and ON requires the use of a specific treatment. Nine randomized controlled clinical trials against placebo performed exclusively for MS exacerbations or acute ON were identified. Corticosteroids or ACTH produced a significant improvement in disability or vision at 30 days and shortened the duration of exacerbations. Longer follow-up clinical trials performed in MS exacerbation were not able to clearly demonstrate a significant effect. In acute ON clinical trials the long term visual outcome was not significantly different after steroid treatment than after placebo but this outcome is usually good. There is some evidence that high doses of intravenous methylprednisolone delay the occurrence of the next relapse, and have a dose-dependent effect on the rate of new lesion formation. There is no convincing evidence of the effectiveness of oral steroids in MS exacerbations but this treatment is associated with an increase relapse rate in ON. Side effects with intravenous methylprednisolone are less severe than with oral mega doses or ACTH. PMID- 11787366 TI - [Treatment of remitting forms of multiple sclerosis]. AB - Disease-modifying treatments in multiple sclerosis emerged during the last few years, concerning mainly relapsing-remitting forms of the disease. They are essentially represented by beta-interferons. beta-interferons reduce relapse rate, achieving about 30 p. cent, and have an effect on brain lesions detected on MRI. They are indicated for use in ambulatory patients with relapsing-remitting multiple sclerosis characterized by at least 2 attacks of neurological dysfunction over the preceding 2 (or 3)-year period. Questions and controversies still remain concerning dose-response effect, early initiation and duration of treatment. Copolymer, which has a different mechanism of action, also decreases frequency of relapses, and the magnitude of the clinical effect is similar to beta-interferon. Copolymer is indicated for use in patients with relapsing remitting multiple sclerosis, having either an intolerance or a contra-indication to beta-interferon. PMID- 11787367 TI - [Obesity in 2000]. PMID- 11787368 TI - [Obesity and cardiovascular risk]. AB - Overweight and obesity are recognised as responsible for an increase in vascular risk and in excess mortality due to cardio-vascular diseases. This is especially true in presence of increased visceral (central) fat distribution, a key factor for insulin-resistance, the main component of the metabolic syndrome X. Cardio vascular risk in overweight and obese subjects appears strongly correlated with the common risk factors, more frequently present in these patients: type 2 diabetes, hypertension, lipid abnormalities. Weight reduction improves all risk factors and decreases the patient's global vascular risk. The improvement in the various risk factors is significant with a moderate weight loss (10% of the initial weight). Weight reduction should been obtained always with nutritional hygienic means (physical activity, weight-reducing diet...) maintained for several months. Only when these approaches appear to be insufficient, the need for an associated pharmacological treatment has to be considered. Amongst the weight-reducing drugs currently available or close to be, orlistat has demonstrated its interest in the glycemic control of type 2 diabetic patients, and its favourable effect in hypertensive patients. Available clinical studies have clearly shown the more marked effect of orlistat in comparison to placebo in reducing the various risk factors. So far, few studies have been conducted to assess the effects of the specific drug therapy on the control of metabolic abnormalities and risk factors in overweight or obese patients, except in type 2 diabetic patients for whom, most of the oral anti-diabetic agents have been tested in overweight or obese diabetic population. PMID- 11787369 TI - [Surgery for obesity]. AB - With the development of new surgical techniques (laparoscopic procedure, adjustable gastric banding) bariatric surgery is still increasing. In France about 10,000 adjustable gastric banding have been performed during the last year, as well as a thousand of gastric operations and approximately fifty gastric by pass. The surgical approach has a real efficacy on weight loss and is associated with a reduction in comorbid conditions. However its long-term efficacy, its effects on quality of life, its nutritional consequences and the surgical-linked complication incidence are only poorly evaluated, especially for adjustable gastric banding. Therefore bariatric surgery indications should be thoroughly examined. As recommended by the experts, surgical treatment for obesity should be restricted to patients presenting morbid obesity, and this despite a multidisciplinary medical treatment. Long-term post-surgical follow-up is necessary and may be an important determinant of long-term efficacy. Considering the growing number of this type of intervention outside of any evaluation, a national register is recommended. PMID- 11787370 TI - [Physical activity and management of obese patients]. AB - Physical activity is recognized as an integral part of obesity treatment, in association with other therapeutic means. A major benefit of physical activity is the association with better long-term maintenance of weight loss. Physical activity has also positive psychological effects and increases quality of life. An evaluation of the usual level of physical activity and inactivity is needed for each patient. Physical activity counselling should be individualized and graded, in a perspective of individual progression. In subjects with massive obesity, remobilization based on physiotherapy techniques is the first step. All patients should be given simple advice to decrease sedentary behavior: use the stairs instead of the escalators, limit the time spent seated, etc. In general, current physical activity recommendations for the general population fit well with a majority of obese patients, i.e. a minimum of 30 minutes/day of moderate intensity physical activity (brisk walking or equivalent) on most, and preferably all, days of the week. Physical activities of higher intensities (endurance training programme) can be proposed on an individual basis. The type of physical activity required for long-term weight maintenance, and the question of adherence to physical activity recommendations in obese patients should be further investigated. PMID- 11787371 TI - [Does obesity protect against diabetes? A new controversy]. AB - Obesity is a risk factor for the appearance of type 2 diabetes: this notion, largely based on clinical experience, dictates the essential principles of the treatment of type 2 diabetes. At odds with this conventional wisdom, Elliot Danforth Jr. has recently proposed that "too few adipocytes predisposes to type 2 diabetes". A further thought on this controversy is discussed herein. In the context of the "orthodox" view which links obesity and diabetes, and its relation to the controversy, we analyse on one hand the effects of thiazolidine-diones on insulin sensitivity and on adipogenesis and, on the other hand, those of extreme situations represented by lipoatrophic diabetes and morbid obesity. This analysis shows that fat tissue indeed favors the appearance of diabetes but is also able to be anti-diabetogenic, and a dynamic solution of this paradox is put forward. We propose a dual evolutionist hypothesis leading to the selection of an intermediary adipogenic genotype based on the limitation of both insulin secretion and adipogenic potential, which would explain both the necessity of the existence of adipose tissue in man and the limitations of its development. PMID- 11787372 TI - [Lipid metabolism in adipose tissue: adrenergic control of the adipocyte and mobilization if the lipids]. PMID- 11787373 TI - [Can we modify colonic microflora and to what end?]. PMID- 11787374 TI - [Palliative endoscopic treatment of pancreatic carcinoma]. PMID- 11787375 TI - [Resectability of pancreatic head adenocarcinoma]. PMID- 11787376 TI - [Dysfunction of the Oddi's sphincter]. PMID- 11787377 TI - [Prognosis of pancreatic adenocarcinoma]. PMID- 11787378 TI - [Old and new physiopathological concepts of irritable bowel syndrome]. PMID- 11787379 TI - [Visceral sensitivity and functional bowel disorders: physiopathological role and therapeutic perspectives]. PMID- 11787381 TI - [Treatment of idiopathic constipation]. PMID- 11787380 TI - [Functional intestinal disorders and quality of life]. PMID- 11787382 TI - [Colonic microflora: composition, substrates, metabolism]. PMID- 11787383 TI - [Palliative surgery of pancreatic adenocarcinoma]. PMID- 11787384 TI - [Molecular analysis of the colonic microflora]. PMID- 11787385 TI - [Colonic microflora and cancer]. PMID- 11787386 TI - [Colonic microflora and motility. Physiological data and during irritable bowel syndrome]. PMID- 11787387 TI - [Intestinal microflora and chronic inflammatory bowel diseases]. PMID- 11787388 TI - [Role of prebiotics and probiotics in therapeutic management of cryptogenetic inflammatory bowel disease]. PMID- 11787390 TI - Are we ready to respond? Assessing nursing's bioterrorism preparedness. PMID- 11787389 TI - [Effects of colonic fermentation on carbohydrate and lipid metabolism]. PMID- 11787391 TI - Nurses share accounts of 9-11 aftermath. PMID- 11787392 TI - Environmentally healthy homes and communities. Children's special vulnerabilities. AB - We like to think that our homes are a safe haven. However, in recent years we have been discovering that certain products, designs, and even the siting of our homes can create health risks. When families moved into a new development in Waynesville, NC, called "Barber Orchard," they were ecstatic about their new surroundings--the fresh air, mountain views, and clean water. When one of the new residents had his well water tested, their dream homes took on a different character. The water was reflective of the years of pesticide use on the former orchard on which their homes were sited; it contained DDT, DDE, and benzene hydrochlorides (Manual, 2000). The soil was contaminated with lead and arsenic, also the result of pesticide applications. The Environmental Protection Agency (EPA) sent in an emergency response team, removed toposil, and advised residents to install carbon filters on their water systems. Sometimes, we unintentionally bring pollution into our homes. In the homes of middle-income families with small children, vacuum dust was found to have pesticide concentrations 10-100 times greater than those found in the surface soils surrounding their houses (Lewis et al, 1994). In the agricultural area of Washington State, 47 of 48 farm homes had chlorpyrifos (an organophosphate pesticide) measured in the house dust. The human health risks associated with chlorpyrifos are substantial (including headaches, dizziness, muscle twitching, vomiting, and blurred vision); hence, in 2000, the EPA eliminated the widely used pesticide for nearly all-household purposes. The purpose of this independent study module (ISM) is to introduce the reader to basic concepts and issues associated with environmental health risks to children in homes and communities. In this ISM, some of the key hazardous exposures occurring in the home will be discussed. Indoor air quality, drinking water, lead, mercury, pesticides, radon, and UV radiation have been selected as topics of focus. A resource section provides a brief listing of resources; many of them are Web sites, which, in turn will link the reader to additional resources. The EPA's Web site is particularly helpful. The University of Maryland School of Nursing has a new Web site, http://enviRN.umaryland.edu, with links to all of the Web sites noted in this ISM. PMID- 11787393 TI - Mandatory overtime bill caps off successful legislative year. PMID- 11787394 TI - Caregiver suffering is a dimension of end-of-life care. PMID- 11787395 TI - [History of the Spanish Neurosurgery Society (SENEC, formerly SLEN]. PMID- 11787396 TI - [Endoscopic treatment of suprasellar arachnoid cysts]. AB - Arachnoid cysts account for only 1% of all intracranial space-occupying lesions. In adults suprasellar cysts represent 9% of all the arachnoid cysts while in pediatric population this percentage reaches 15%. In spite of being a problem relatively common in daily neurosurgical practice there are still a number of questions to be solved concerning pathogenesis and evolution, natural history and treatment. Located in the suprasellar cistern and closely related to the ventricular system, suprasellar arachnoid cysts conform a perfect indication for endoscopic treatment. The development and spreading of neuroendoscopic techniques have surpassed the standard microsurgical approaches as an elective treatment. However there is still controversy on the management of associated hydrocephalus, need for cystoperitoneal shunt after endoscopic fenestration or the superiority of ventriculocystocisternostomy over simple ventriculocystostomy. The authors present a serie of seven consecutive patients with "de novo" diagnosis of suprasellar arachnoid cyst. In every case the treatment consisted in endoscopic fenestration and removal of the cyst membranes, with or without associated ventriculostomy of the IIIrd ventricle. Preoperative symptoms improved in all the patients and five out of seven remain shunt free. One patient maintains a cystoperitoneal shunt and another one, previously shunted, remains shunt dependent. The clinical presentation and postoperative evolution are commented with discussion on the alternative therapeutic options from the endoscopic point of view. PMID- 11787397 TI - [Spinal neuronavigation. Our experience]. AB - The spinal column has been considered ideal for guided surgery due to its stable anatomical structure and notable reference points which are perfectly distinguishable both in computer tomography (C.T.) images and in the surgical field. Our main objective was to apply this technique to the conventional transpedicular fusion surgery. During the last year (1999), 13 males and 26 females, with an average of 47.1, + 14.1 years were operated because of degenerative discopathy (9 cases) degenerative discopathy associated to listhesis (7 cases) and spinal canal stenosis (8 cases). All of them were operated according to a preestablished protocol using the Brain Lab Image Guided System. The preestablished protocol could not be applied in 3 patients. Of the 36 patients, only in 22 cases (61%), a properly navigation was obtained. In these cases 116 screws were used: 108 (93%) strictly intrapediculars. In the other 14 patients, without Guided Surgery, it was used 76 screws: 65 (86%) were strictly intrapediculars. In our opinion Guided Spine Surgery, offers an accuracy and reliability to reduce the margin of error in the Transpedicular location of the Spine Fusion Systems. PMID- 11787398 TI - [Subarachnoid hemorrhage secondary to dissecting aneurysms of the vertebral artery. Description of 2 cases and review of the literature]. AB - OBJECTIVES AND INTRODUCTION: The pathogenesis and natural history of intracranial vertebral artery dissection remain uncertain up to now due in part to its relative rarity. In this article we review the state of the art of this process and remark the good outcome obtained with embolization using Guglielmi detachable coiling (GDC). METHODS: Two cases with subarachnoid hemorrhage secondary to rupture of a vertebral dissection aneurysms are described. The first patient initially suffered brain stem infarction, followed by a subarachnoid hemorrhage a year later. The second patient who had a severe subarachnoid hemorrhage with two early rebleedings was successfully treated with embolization using GDC. CONCLUSIONS: Subarachnoid hemorrhage due to rupture of vertebral dissecting aneurysm is a relatively unknown disease with some important aspects that should be known. The high incidence of early rebleeding (up to 60%), makes early diagnosis and treatment important goals. Classically the preferred treatment has been proximal vertebral artery occlusion. However, the recent introduction of embolization with GDC has made possible the occlusion of the dissection with very good final outcome. PMID- 11787399 TI - [Epidural lumbar hematoma, epidural anesthesia and low-molecular-weight heparins]. AB - Epidural hematoma is an uncommon but serious complication of epidural anaesthesia. The use of low molecular weight heparin (LMWH) as thromboprophylaxis has increased the occurrence of this pathology. We report the case of a 81-year old man who underwent an arthroscopy of the knee, with epidural anaesthesia and administration of LMWH. The patient suffered an important pain due to a lumbar epidural haematoma which was diagnosed by magnetic resonance, after withdrawal of the epidural catheter. He improved after surgical evacuation, and no neurological deficit was present. We comment the association of LMWH, epidural anaesthesia and epidural haematoma. PMID- 11787400 TI - [Endoscopic fenestration as a treatment for asymmetrical hydrocephalus due to obstruction of the foramen of Monro]. AB - Unilateral dilatation of the lateral ventricle is a rare condition. The most common causes are tumors of the lateral ventricles or in the area of the third ventricle, acute or chronic inflammatory gliosis, cysticercosis or congenital atresia of the foramen of Monro. We report a case of asymmetrical dilatation of the lateral ventricle in an adult patient presenting with a raised intracranial pressure syndrome caused by narrowing of the foramen of Monro which was occluded by a thin membrane. The patient underwent successful endoscopic fenestration of the Foramen of Monro. PMID- 11787401 TI - [Occipital condyle fracture without neurological deficit: apropos of a case]. AB - Fracture of the occipital condyles is a rare pathology that can be easily undiagnosed. The bibliographic references on this theme are scarce and the majority are related to patients with palsy of the low cranial nerves and/or a high cervical subluxation with abnormal posture of the neck. The authors describe one case of the occipital condyle fracture without clinical manifestations other than persistent pain, and without alterations of the high cervical region. The patient was submitted to conservative treatment by means of a cervical collar due to the existence of minor symptoms. The clinical criteria that should lead to the study of this pathology are discussed, just as the use of a computerized tomography bone window as the fundamental instrument in its diagnosis and classification. PMID- 11787402 TI - Parosteal osteosarcoma of the skull. AB - Parosteal osteosarcoma of the skull is a distinct surface bone tumor, with a better prognosis than conventional osteosarcoma. The most common location is on the surface of the distal femur which accounts for 46-66% of the cases. The presentation in the skull is uncommon and there are few cases reported in the literature. We describe the case of a man who developed a parosteal osteosarcoma arising from the occipital bone with extension to the parietal bone. The patient was operated and had a complete tumor resection. PMID- 11787403 TI - [Symptomatic xanthograuloma of the lateral ventricle]. AB - Xanthogranulomas of the choroid plexus in the lateral ventricle are usually asymptomatic lesions found incidentally at autopsy. Symptomatic cases are rare. We present the case of a 30-year-old woman with a xanthogranuloma of the right lateral ventricle who showed intracranial hypertension and visual disturbance. Plain T1-weighted magnetic resonance images disclosed a isointense right temporal lesion in the ventricular horn which showed decreased signal intensity on T2 weighted images and massive enhancement on T1-weighted images after gadolinium injection. She was operated on through a right temporal craniotomy with total excision. We review the literature and discuss radiological findings on MRI. PMID- 11787404 TI - [Examining patients]. PMID- 11787405 TI - Management of Parkinson's disease. Strategies, pitfalls, and future directions. AB - In coming years Parkinson's disease will become increasingly prevalent as the baby boom generation grows older. Diagnosis often is complicated and requires careful consideration of symptoms and neurologic findings. Optimal symptomatic treatment of Parkinson's disease involves an individualized approach with each patient and ongoing evaluation of benefits versus side effects. Neurosurgical intervention is an option for some patients who are not adequately helped by medical therapy. New treatments (e.g., stem cell therapy) are currently being studied and may be available in the foreseeable future. PMID- 11787406 TI - Pain in Parkinson's disease. Common yet seldom recognized symptom is treatable. AB - As many as half of all patients with Parkinson's disease experience pain related to their condition. Once this relationship is recognized, the pain can be managed by achieving better control of the disease. In this article, Drs Waseem and Gwinn Hardy discuss the many causes of this type of pain, which include disease complications and primary sensory pain syndromes. They also present and evaluate the treatment options available. PMID- 11787407 TI - Are these pigmentary changes only cosmetic? Oculodermal melanocytosis (nevus of Ota). PMID- 11787408 TI - How reliable are bone densitometry results? PMID- 11787409 TI - Estimating the glomerular filtration rate. Dos and don'ts for assessing kidney function. AB - The National Kidney Foundation's guidelines for CKD make the following recommendations about assessment of kidney function. Estimates of GFR are the best overall indices of the level of kidney function. The level of GFR should be estimated from prediction equations that take into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. In adults, the MDRD study and Cockcroft-Gault equations provide useful estimates of GFR. In children, the Schwartz and Counahan-Barratt equations are useful. The serum creatinine concentration should not be used alone to assess the level of kidney function. Clinical laboratories should report an estimate of GFR using a prediction equation, in addition to reporting the creatinine measurements. Autoanalyzer manufacturers and clinical laboratories should calibrate serum creatinine assays using an international standard. Measurement of creatinine clearance using timed (e.g., 24-hour) urine collections does not improve the estimate of GFR over that provided by prediction equations. A 24-hour urine sample provides useful information for estimation of GFR in individuals with exceptional dietary intake (vegetarian diet, use of creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting). It is also useful for assessment of diet and nutritional status and need to start dialysis. PMID- 11787410 TI - Legislating health. Are government regulations the key to ensuring the delivery of quality care? PMID- 11787412 TI - Patient notes: febrile seizures. PMID- 11787411 TI - Timing treatment to the rhythm of disease. A short course in chronotherapeutics. AB - The recognition of circadian rhythms in both normal human biologic function and disease has heightened the awareness that the timing of drug regimens may have an important impact on effectiveness of treatment. Outcomes in several diseases that have predictable circadian variations (e.g., arthritis, asthma, allergies, pepticulcer disease, dyslipidemia, cancer) have been improved by matching the timing of medication use to the circadian rhythm of the illness. Results of the ongoing CONVINCE study may provide evidence that chronotherapy for hypertension and angina pectoris may be more effective than traditional homeostatic treatment. PMID- 11787413 TI - Type 1 versus type 2 diabetes: still a useful distinction? PMID- 11787414 TI - Timely intervention in asymptomatic aortic stenosis. Emerging clinical parameters may help predict outcomes. AB - In determining the optimal time to intervene in asymptomatic patients with aortic stenosis, physicians need to take into account the clinical course of the disease, the risks of surgical intervention, and the long-term consequences of prosthetic valves. In this article, Dr Park reviews the pathology of aortic stenosis, methods of diagnosis, and predictors to help identify patients who may benefit from early surgical intervention. PMID- 11787415 TI - Mysteries of mitral valve prolapse. Proper treatment requires consideration of all clues. AB - Although mitral valve prolapse is common in developed countries, its prevalence and its complications are much lower among the general population than was previously thought. No association has been conclusively documented for a myriad of neuropsychiatric symptoms previously speculated to be associated with mitral valve prolapse. Moreover, the prevalence of mitral valve prolapse does not appear to be affected by male or female sex. The most important management issues are mitral regurgitation and antibiotic prophylaxis for procedures that can cause bacteremia. For patients who are asymptomatic, reassurance becomes a critical component of treatment. If symptoms develop because of severe mitral regurgitation and decreased cardiac reserve, surgery may be required. PMID- 11787416 TI - Native mitral valve regurgitation. Proactive management can improve outlook. AB - Mitral regurgitation is a common valvular abnormality that can result in substantial morbidity. Primary care physicians should maintain a high index of suspicion for this disorder, especially in patients with symptoms of heart failure. The paramount concern is early identification of patients with mitral regurgitation and prompt referral to a cardiologist when symptoms occur or if evidence of ventricular enlargement or reduction in ejection fraction is found. Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Although no standard medical treatment has been established for mitral regurgitation, use of ACE inhibitors is appropriate. Patients presenting with severe, acute mitral regurgitation from papillary muscle rupture should be evaluated for ischemia and treated expediently. The preferred operative procedure in patients with severe mitral regurgitation and left ventricular dysfunction is mitral valve repair, if possible, or mitral valve replacement with posterior chordal preservation, if feasible. PMID- 11787417 TI - Valvular heart disease and pregnancy. A high index of suspicion is important to reduce risks. AB - Pregnant women who have valvular disease represent a major challenge for physicians involved in their care. Careful history taking and physical examination, along with a judicious use of diagnostic tools (mainly echocardiography), can lead to better management and ultimately to excellent outcomes for both mother and baby. PMID- 11787418 TI - Cracking a dyspnea mystery. Drug-induced pulmonary fibrosis. PMID- 11787419 TI - Pain management for dying patients. How to assess needs and provide pharmacologic relief. AB - Patients at the end of life need not have unrelieved pain. Thorough assessment and multidisciplinary treatment can provide comfort with a minimum of adverse effects. Patients and their families can be freed to accomplish their final goals, and the bereaved families can be spared the pain of memories of loved ones who suffered in their final days. PMID- 11787421 TI - [Identification and molecular characterization of a Toxoplasma gondii microneme]. AB - Protozoan of the phylum Apicomplexa are of high medical and veterinary importance, causing diseases such as malaria, toxoplasmosis and cryptosporidiosis. Invasive stages of apicomplexans possess organelles named micronemes, which are involved in the invasion process. We have recently characterized a protein in micronemes of Toxoplasma gondii, TgMIC3, which possess adhesive properties to host cell surface. Immunofluorescence analysis of T. gondii tachyzoite invasion showed that TgMIC3 is exocytosed and re-localised on the surface of the parasite during invasion. By being able to bind both the putative host cells and the parasites, TgMIC3 could be involved in invasion by acting as a bridge between the parasite and the host cell. Gene sequence analysis of TgMIC3 has revealed 5 partially overlapping EGF-like domains and a lectin binding-like domain, which can be involved in protein-protein or protein carbohydrate interactions respectively. TgMIC3 is a homodimer synthetized with a N-terminal propeptide that is cleaved during trafficking to the organelle, presumably in the trans-Golgi network. The processing involves a serine protease and is required for correct binding function of TgMIC3. The exact role of this propeptide remains unexplained. It may be involved in the targetting of the protein to the micronemes by masking the region involved in interaction with membranes to avoid binding of the protein in the trafficking pathway. PMID- 11787422 TI - [Mitogen activated protein kinases (MAPK) and Toxoplasma gondii host cell invasion]. AB - Toxoplasmosis is still a big concern in Public Health in France, regarding two particular aspects: congenital toxoplasmosis and reactivated toxoplasmosis in immunodeficient patients. Toxoplasma gondii is an obligate intracellular parasite, that can invade almost all nucleated cells. The invasion step has been widely studied, but its accurate mechanism and the cell receptor remain largely unknown. In this work, we have attempted to investigate the role of kinases and signal transduction in the host cell penetration. We characterized mitogen activated protein kinases (MAPK). in the parasite itself by immunoblotting, immunofluorescence, and determination of enzymatic activity. In particular, we identified two proteins of 43 and 47 kDa, that could be homologues of extracellular signal-regulated kinases (ERK), i.e. ERK2 and ERK1, respectively. These parasite MAPK are activated by calcium and phorbolmyristyl acetate and inhibited by RO 31-8220, suggesting an activation through protein kinases C (PKC). Indeed the MAPK kinase (= MEK) inhibitor PD98059 inhibits the activation of parasite MAPK, suggesting that a MEK homologue could be responsible for the dual phosphorylation of MAPK on tyrosine and threonine residues, necessary for their activation. Finally, we demonstrated that activation or inhibition of parasite MAPK by preincubation of parasites with various activators or inhibitors led to an increased or reduced host cell invasion in vitro by parasites, respectively. All these results are in favour of a role of ERK-type parasite kinases in T. gondii infectivity in vitro. PMID- 11787423 TI - [Cryptosporidium parvum: functional study of the intestinal malabsorption syndrome]. AB - Cryptosporidiosis is an important cause of diarrhea associated with growth retardation in children and severe malnutrition in immunocompromised patients. The pathophysiology is poorly understood. In the suckling rat model, we show that C. parvum infection impairs net electrogenic transport across the ileal mucosa without involvement of prostaglandins, as well as trans- and paracellular permeability and leucine and glutamate absorption. These results provide evidence for the development of an intestinal malabsorptive syndrome during cryptosporidiosis. Unspecific process such as villous atrophy and inflammatory cytokines secretion should be regarded as possible mediators of this syndrome. However, specific mechanisms have to be considered since C. parvum induces a rearrangement of the host enterocyte cytoskeleton which might impaired intracellular trafficking thus reducing the membrane expression of nutrient transporters. Infection and malnutrition are known to be tightly associated, making each other worse. As no specific efficient therapy exists, cryptosporidiosis-induced malnutrition must be taken into account when establishing therapeutic scheme. PMID- 11787424 TI - [Plasmodium falciparum: point mutations of pcfrt and chloroquine susceptibility]. AB - Recent transfection based studies demonstrated that cg2, a candidate gene for chloroquine resistance in Plasmodium faiciparum, was not the resistance determinant. A further analysis of the initial 36 kb locus comprising the cg2 gene led to the discovery of another gene, pfcrt, which was absolutely associated with chloroquine resistance in forty parasite lines. The aim of this study was to evaluate, in 146 unselected clinical isolates obtained mostly from non-immune travellers returning from various endemic countries to France in years 1995-1999, the association between in vitro chloroquine resistance and the sequence of a part of the pfcrt gene. For comparison, the determination of the cg2 kappa and the pfmdr1 codon 86 genotypes were also performed on the same isolates. As determined by an isotopic semi-microtest, 70 isolates were susceptible to chloroquine (50% inhibitory concentration < 80 nM) and 76 were resistant. The amplification of a portion of the pfcrt gene spanning codons 72 to 76, followed by sequencing showed three distinct genotypes: one type associated with susceptible isolates, one type associated mostly with resistant isolates and one type found in a resistant isolate originating from South America. Three different zones could be defined according to the status of codon 76. For 50% inhibitory concentration values < or = 40 nM (n = 47), all isolates but one had K76 (wild type). For 50% inhibitory concentration values located between 40 and 60 nM, isolates had either K76 (n = 5) or K76T (mutant type) (n = 6). For 50% inhibitory concentration values > 60 nM (n = 88), all isolates had K76T. A lack of a strong association between the pfmdr1 N86Y mutation and in vitro chloroquine resistance was observed. Cg2 genotypes were less strongly linked than pfcrt genotypes with in vitro chloroquine susceptibility in isolates located below 40 nM and above 60 nM. Further studies are needed to determine the reliability of the pfcrt gene as a genetic marker for chloroquine resistance. PMID- 11787425 TI - [Prevention and treatment of malaria: in vitro evaluation of new compounds]. AB - One of the current options for reducing the morbidity and mortality of malaria are chemoprophylaxis and chemotherapy. For this reason, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria. There is an urgent need to find and develop novel compounds and to identify novel chemotherapeutic targets. Different approaches to discover new compounds are presented from examples of molecules studied in the Tropical Medicine Institute of the French Army Health Service (IMTSSA) evaluation against isolates of compounds in pharmaceutical development in collaboration with pharmaceuticals (pyronaridine, benflumetol, ferrochloroquine), screening of molecules which are still registered for other pathologies (antibiotics), screening of new synthesized compounds (artemisinin derivatives) and identification of parasitical targets and essential metabolic ways for parasite, and identification of molecules acting on these targets (reversal of resistance to chloroquine, iron chelators). PMID- 11787426 TI - [Safety assessment of new products developed by the pharmaceutical industry]. AB - Safety assessment of new products developed by the pharmaceutical industry is a scientific, ethical and economic requirement. The finality is an assessment of the benefit/risk ratio of these products, a fundamental issue for their registration. Conventional studies, such as defined by ICH guidelines, and their timing versus clinical trials are reported here. General conditions for management and cost are discussed. Nevertheless, these conventional studies are poorly adapted to current requirements due to insufficient throughput and lack of discriminating potential. Consequently, new tools are being proposed (genomics, proteomics, metabonomics, etc.), allowing, for example, a faster and more relevant screening of leading compounds designed to be administered in humans in clinical trials. Nevertheless, these tools are complex, expensive and probably reserved for the largest companies. A well-balanced approach, including the choice of reasonable objectives, should enable rapid enrichment of our assessment potential, excluding abrupt, unproductive and premature changes. PMID- 11787427 TI - [The mechanism of action of isoniazid. A chemical model of activation]. AB - The antituberculosis drug isoniazid (INH) is quickly oxidized by stoichiometric amounts of manganese(III)-pyrophosphate. In the presence of the nicotinamide coenzyme, the INH oxidation produced the formation of INH-NAD(H) adducts which are potential competitive inhibitors of the enoyl-acyl carrier protein reductase InhA, an INH target in the biosynthetic pathway for mycolic acids. Manganese(III) pyrophosphate is an efficient alternative oxidant to mimick the activity of the Mycobacterium tuberculosis KatG catalase-peroxidase and will be useful for further mechanistic studies of INH activation and for structural investigations on reactive INH species and resulting InhA inhibitors. PMID- 11787428 TI - [Ground and first singlet excited dissociation constants of 4 methylumbelliferone: application for indirect spectrofluorimetry of nitriles and nitrosamines]. AB - The light adsorption process provides important changes in the electronic configuration of molecules. For phenolic derivatives, light adsorption contributes to acidity in the excited state. In aqueous medium, excitation of the molecular form (ArOH) undergoes dissociation at the first singlet excited state and subsequent fluorescence emission occurs from the excited ionized form (ArO *). The emission is higher than from the molecular form and exhibits a shift to the red. The combination of these two phenomena allowed simultaneous increase in selectivity and sensitivity. In addition this method allowed an easy quantification of 4-methylumbelliferone at the nanomolar level and consequently trace levels of nitrates and N-nitrosamines after diazotization and/or denitrozation. PMID- 11787429 TI - [Urinary nandrolone metabolites in antidoping control]. AB - The French National Laboratory of the International Olympic Committee (IOC) has detected norandrosterone (NA) and noretiocholanolone (NE) in urine samples from several sportsmen. These two substances are known to be urinary metabolites after nandrolone intake. In such cases, the NA level is always higher than the Ne level. However, in the urine samples of sportsmen tested positive, the NE concentrations were systematically higher than the NA levels. We therefore searched for other steroid precursors (commercially available capsules or tablets of dehydroepiandrosterone, 4-androstenediol, 5-androstenediol, 4-androstenedione, 19-norandrostenediol and 19-norandrostenedione, also illegally used in France) which could lead to an excretion of NA and NE and to an inverted ratio of these metabolites. PMID- 11787430 TI - [Radioimmunoassay of testosterone concentrations in hair: use in doping control]. AB - The measurement of doping agents in hair is attractive since it offers an increase in retrospective detection of doping with these substances. Hair analysis has a wide window of detection, ranging from months to years, depending on the length of the hair shaft and provides information concerning the pattern of an individual's drug abuse. The aim of the present study was to evaluate the ability of a radioimmunological method to determine physiological concentrations of testosterone in hair. Specimens of hair were collected from four children, nine women and twelve men. None of the subjects was an athlete. Hair samples were weighed, decontaminated and digested in sodium hydroxide. The homogenates were extracted by organic solvent. After evaporation, testosterone was measured by radioimmuno-assay. Hair testosterone concentrations ranged 0.6-2.7 pg/mg, 1.8-6.4 pg/mg and 3.6-23.3 pg/mg for children, women and men respectively. This method is fast and accurate and could have applications in doping control, for screening easily numerous hair samples. GCMS is absolutely necessary to confirm results above 30 pg/mg. PMID- 11787431 TI - [How and why does the metabolic equilibrium of the mother affect the embryo?]. AB - Prevalence of congenital malformations in infants born to women with diabetes mellitus remains high (between 6 and 10%), which is between 3 and 5 times higher than in the general population. Major congenital anomalies are 7 to 10 times more frequent in infants born to diabetics. Normal pregnancy is a state of metabolic stress that requires a high degree of maternal physiological adaptation to help optimize fetal growth. Decreased insulin sensitivity throughout pregnancy with reactional hyperinsulinism helps metabolic efficiency. Changes are observed in glucose, lipid and protein metabolism during pregnancy with a rapid switch from anabolism to catabolism. Diabetic women have absolute or relative insulin deficiency and display abnormalities in carbohydrate, lipid and protein metabolism. These abnormalities can adversely affect embryo growth and explain the high prevalence of spontaneous abortions and congenital malformations. There is a multifactorial origin, of which hyperglycemia in early embryo development is the most important. Hyperglycemia-induced malformations are mediated by sorbital accumulation, arachidonic acid and myoinositol deficiencies and high concentrations of beta-hydroxybutyrate. Accumulation of free oxygen radicals by increased formation and decreased clearance may serve as metabolic common denominators for teratogenic processes. Other factors such as zinc deficiency, the presence of somatomedin inhibitors and released TNF alpha are candidates. Human clinical studies are not consistent with a genetic predisposition to diabetes-related malformations. Progress is needed in pre-conception care of diabetes and blood glucose must be strictly controlled during early pregnancy. PMID- 11787432 TI - Metabolic impact of puberty on the course of type 1 diabetes. AB - Puberty is characterised by important physiological and hormonal changes. In type 1 diabetes, abnormalities in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis play a important role. Spontaneous hyper-GH secretion arises, with reduced circulating IGF-1 levels, both leading to a reduction in insulin sensitivity. From a clinical point of view, these abnormalities are linked to a deterioration glycaemic control, often more marked in females (in whom the degree of insulin resistance during puberty seems to be higher). These abnormalities in the GH/IGF-1 axis in may constitute a risk for the development of microangiopathic complications. Optimisation of insulin therapy has practical limitations and intensification of insulin therapy poses problems (weight gain, nocturnal hypoglycaemia). Several alternative therapeutic approaches have been explored to restore insulin sensitivity, either through a direct effect on the GH/IGF-1 axis, or through drugs with a direct insulin sensitivity effect, but all these approaches remain to be confirmed and the safety and acceptability of these treatments to be established on a long-term basis. PMID- 11787434 TI - [The adolescent and diabetes: diabetes works me up"]. AB - Diabetes, a chronic disease, is a heavy burden for adolescent patients. One has to bear this in mind, day after day. First of all, an adolescent does not wish to be diabetic and the doctor keeps reminding him that he is diabetic. Facing this inadequacy, the adolescent is reluctant to develop a confident relationship with his doctor and compels us to question our practice. Adolescence is a period of life when are revealed to the individual the problems of dependency often emerging into various pathologies of "acting", a period marked by the pressure of the sex drive. The process of subjectivation necessary to adolescence allows the appropriation of a sex-endowed body and of an autonomous and creative thought together with distance towards others and towards one's impulses. On the contrary, the treatment of diabetes increases passiveness and dependency and crystallizes the conflicts of adolescence. Some adolescents try to accommodate this relation of dependency by adopting either an opposing behaviour or other mental defences like splitting or denying. They are led to faking their log book or to deluding themselves about the recognition of their diabetes. This is a way of keeping their illness at a distance, of putting it aside and perhaps of protesting part of their narcissism. Of course, this difficulty of undergoing the treatment must be talked over with them in so far as what is valuable for diabetes control is not necessarily so for their psychic equilibrium at this stage of their life. PMID- 11787433 TI - [Interdisciplinary management of the diabetic adolescent. "Between two balances"]. AB - Insulin-dependent diabetes mellitus (IDDM) is difficult to live with as well as difficult to treat among adolescents. The physiological and psychological changes, that characterize the transition from childhood to adulthood, are often accompanied with deterioration in glucose control. This disequilibrium is linked, on the one hand, with the hormonal phenomena caused by puberty and, on the other hand, with behavioral factors. The strict way of living together with the daily constraints imposed by the treatment become hardly in keeping with the fundamental needs of freedom and self-sufficiency of the adolescent. The treatment of the diabetic adolescent requires a good insight in the specificities of adolescence as well as a good knowledge of diabetes at this period of life. The objective of the treatment and the approach of the patient will have to be adapted to this age and not simply modeled on the diabetological practices commonly used with children or adults. For every patient suffering from a chronic disease, and even more so for adolescents, the treatment of the disease in its biomedical aspects is necessary but not sufficient. The interactions between the adolescent patient, his illness, his treatment and his environment work in such a way that they can only be taken into account globally. Only a close cooperation and atmosphere of give and take between this adolescent, who is in fact the principal agent of his treatment day after day, and the different persons taking care of him, can prove effective. In practice, this can be really achieved by the medical team only if their indispensable technical competence is combined with an all-important approach centered on the patient as an individual. PMID- 11787435 TI - [Which contraception to choose for the diabetic woman?]. AB - Low-dose oral contraceptives can be used by a great number of women with IDDM or a previous gestational diabetes mellitus. Others hormonal contraceptives (progestogen-only preparations) are less convenient and the compliance is poor with an increasing risk of gynaecologic side effects. The safety of this contraceptives as regards vascular diabetic complications is not evaluated well. Nulliparous patients with progressive complications can use barrier methods of contraception after education. Macroprogestative contraception is a adequate choice for women within forties. For multiparous diabetic women, intra-uterine devices represent the first choice. PMID- 11787436 TI - [Management of diabetic nephropathy before and during pregnancy]. AB - Congenital malformations represent the major risk of pregnancy in diabetic women. Prevention needs strict glycemic control before and during pregnancy. The risk of maternal and foetal complications is particularly high among patients with diabetic nephropathy, and a multidisciplinary approach is necessary. Before pregnancy, nephropathy is evaluated on serum creatinine and 24 hour urinary albumin and protein excretions. We discuss the interactions between diabetic nephropathy and pregnancy: the care of the other diabetic complications, the course of renal function during and after pregnancy, the influence of nephropathy on maternal and foetal complications and prevention of the latter by strict control of blood pressure and glycaemia before and during pregnancy. All these elements should be taken into account when discussing pregnancy with diabetic women with nephropathy wishing to become pregnant. The need to take preventive measures should be emphasised but the practice of systematically discouraging pregnancy without careful evaluation should be avoided. PMID- 11787437 TI - [Management of diabetic complications during pregnancy using diabetic retinopathy as an example]. AB - Pregnancy may adversely affect the natural course of diabetic retinopathy (DR). Reported rates of new cases or progression of DR during pregnancy range from 10% to 70%. Regression of some of the nonproliferative vascular changes have been reported after delivery. Several risk factors contribute to the aggravation of DR, such as pregnancy itself, duration of the diabetes, elevated glycohemoglobin level, degree of retinopathy at the beginning of the pregnancy, rapid normalization of blood glucose level. The mechanisms by which pregnancy may alter the course of DR is not elucidated: worsening of DR may be due to modifications of retinal blood flow, or to increase in circulating growth factors levels. Careful ophthalmologic monitoring during pregnancy is required. Fundus examination should be performed before pregnancy or at the beginning of it. In patients with no retinopathy, fundus examination should be performed every three months. In those with diabetic retinopathy, fundus examination should be repeated every month. In eyes with proliferative DR or severe nonproliferative DR before pregnancy or at its beginning, laser photocoagulation should be performed promptly. PMID- 11787438 TI - [What is the approach to gestational diabetes in 2001?]. AB - In 2001, gestational diabetes (GD) remains the subject of much debate, particularly as regards screening and diagnosis, therapeutic management and effects on perinatal outcome. It continues to be defined as a disorder of glucose tolerance occurring for the first time during pregnancy, whatever the outcome during the post-partum period. There is as yet still no consensus concerning screening and diagnosis criteria, partly due to the existence of a continuum between maternal blood glucose levels and perinatal outcome, which means that any threshold is necessarily arbitrary. There is no general agreement concerning therapeutic management. As regards diet, there are insufficient randomised prospective studies that could serve to establish minimum required calorie intakes and various regimen. Intervention studies should provide more accurate information concerning the role of diet in therapeutic strategies. It is also necessary to define the role of other therapeutic alternatives such as insulin analogues, or more recently, the sulphonylureas. Nevertheless, although there is still a large debate, the physiopathological mechanisms are becoming increasingly clear. GD and type 2 diabetes appear to be the same entity, with the former constituting an early sign of the latter. Long-term management of women with GD and treatment modalities also require better definition, since these patients are at risk for diabetes, mainly type 2. PMID- 11787439 TI - [Insulin therapy in type 1 diabetes for and during pregnancy: by which means and for which objectives?]. AB - Clinical data in the 1980s showed a close relationship between the conceptional glycated hemoglobin and the occurrence of spontaneous early abortions and fetal malformations. Blood glucose level during pregnancy was similarly correlated with the risk of fetal macrosomia, due to significant links between birthweight, fetal hyperinsulinemia and mean maternal blood glucose. Tight blood glucose control from conception to term was shown to be able to lower the risk of fetal malformations and perinatal mortality to that of the offspring of a non diabetic mother. Prerequisites include: 1) contraception until tight blood glucose control, 2) close partnership between diabetologist and obstetrician, 3) assessment of diabetic complications. Seldom, coronary heart disease or advanced nephropathy contraindicate pregnancy. Uncontrolled proliferative or pre proliferative retinopathy, or macular edema, are temporary contraindications to pregnancy. Laser photocoagulation must then be performed before tightening blood glucose control. A complete review of diabetes management is associated with therapeutic intensification. Blood glucose objectives allow as limits: 70 to 100 mg/dl before meals, up to 140 mg/dl one hour and 120 mg/dl two hours after meals. HbA1c allowing conception is close to 7%. Blood glucose monitoring requires 6-7 measurements per day. The most efficient insulin regimens include 3 to 4 shots per day. The distribution between regular and NPH or lente insulins is adapted individually. Lispro insulin, now appearing as safe, may be used to improve post meal blood glucose control. Insulin pumps may be useful in case of late-night poor control or frequent hypoglycemic events. Patient acceptance of this option is unavoidable to obtain a benefit. Preconceptional insulin therapy must be maintained until pregnancy term. Follow-up must be intensified after twenty fourth week. Labor and delivery, cesarean section, fetal maturation by corticosteroids and use of i.v. betamimetic drugs require continuous i.v. insulin delivery. The continuation of intensive insulin management in post-partum is encouraged. PMID- 11787440 TI - [Sexuality of the diabetic woman]. AB - Diabetes Mellitus frankly increases the prevalence of sexual problems in men, mainly in the form of erectile dysfunctions. Its effects on sexual function of the diabetic women have been less objectively studied, due to cultural reasons and methodological difficulties. The different phases of the sexual cycle, as well as their physiological control, are similar in human males and females. Several studies suggest an increased prevalence of sexual problems also in diabetic females. Their rate seems similar to that of the males. An increased prevalence of Female Sexual Arousal Disorder has been found in 6 studies of 6 comparing diabetic to non diabetic females. Its main symptom was a deficient vaginal lubrication, making sexual intercourse unpleasant. This disorder is the female equivalent to erectile dysfunction. It probably results from similar mechanisms, involving damages in the vascular and autonomic nervous systems, as well as alteration in the nitric oxide production and efficacy. The prevalence of Hypoactive Sexual Desire Disorder was also increased in most studies (5 of 8, significantly in 3). This could result from the increased prevalence of depression in diabetic females. The Dyspareunia's prevalence was not significantly increased (0 of 6 studies). Available figures are not consistent as regards the orgasmic disorders (prevalence increased in only 4 of 8 studies). No significant correlation of female sexual dysfunction with diabetes duration, balance, or complications has been found. Conversely some significant correlations with depression or poor acceptance of diabetes have been found, supporting a causative role of psychological factors. Although still limited the therapeutic options should not be neglected. Merely prescribing a water soluble lubricating gel may greatly improve the sexual life of couples. Doctors should talk themselves about sexual function with their female diabetic patients. Most of these are too much embarrassed to ask themselves their doctor, although their sexual problems may seriously interfere with their quality of life and that of their partner. PMID- 11787441 TI - [Resistance to insulin and polycystic ovary syndrome]. PMID- 11787442 TI - [Is cardiovascular risk different in the diabetic woman?]. AB - Cardiovascular disease is a leading cause of mortality among diabetic women. However, studies devoted to cardiovascular disease in women, and particularly diabetic women, are scarce. Diabetes erases the natural protection of premenopausal women against cardiovascular disease. Risk of death from coronary artery disease is higher in diabetic women than in diabetic men. Diabetic women might be more exposed to some risk factors. Non invasive diagnostic tools of coronary artery disease are less accurate in women, and women are less likely than men to undergo catheterization or revascularization. The lower diameter of coronary artery might contribute to these reluctances. Nevertheless, long-term outcome of the revascularization procedures (thrombolysis, bypass graft, angioplasty) are similar in men and women, although peri-procedural risks might be higher in women. Finally, secondary prevention treatments, particularly beta blockers, are underused in women. Gender differences in cardiovascular risk among diabetics are partly explained by discrepancies in terms of coronary artery anatomy or lack of reliable non invasive tests. But the longer delay to treatment and the lack of scientific information about the particular features of coronary heart disease in women probably contribute to the increased risk in diabetic women. PMID- 11787443 TI - [Hormone replacement therapy at menopause in the diabetic woman]. AB - Epidemiological: higher coronary risk in female diabetic patients than in male diabetic patients. Physiopathological: disturbance of lipid metabolism and endothelial nitric oxide (NO) production, seen in both menopausal and diabetic subjects. Hormonal: hyperandrogenism and excessively high blood oestradiol levels in diabetic menopausal women in relation to non-diabetic menopausal women. HRT in menopausal diabetic women Efficacy against climacteric disorders and osteoporosis. No major risks since the effects on lipoproteins are not significant and there are some positive effects on hepatic glucose production during hyperinsulinaemic clamp, provided triglycerides are below 2 mmol/l. Relatively positive effects have been noted in cohort studies such as the Nurses' Health Study and in a study measuring carotid intima-media thickness, but marked bias occurred in recruitment. HRT and coronary disease in diabetic and non diabetic women Harmful effects were noted, particularly in the HERS study, with a higher incidence of fatal and non-fatal thromboembolic and/or coronary events. Other studies are underway using both conjugated equine estrogens (Women's Health Initiative) and SERMs (raloxifen and tamoxifen). PMID- 11787444 TI - The present and the future of clinical psychology in the UK. PMID- 11787445 TI - The present and future of clinical psychology in Germany. PMID- 11787447 TI - The current status of clinical psychology in The Netherlands. PMID- 11787446 TI - Clinical psychology in the adult psychiatry in Denmark. AB - During the 90s' a softening of the dogmas, new orientation and expansion of the psychotherapeutic field have been developed. Decentralisation and specialisation involves interdisciplinary team association that threatens the academic advantages of mono-prefessional fora. However expanded research especially related to specialisation is seen. PMID- 11787448 TI - Clinical psychology: a psychosocial antidote to biological reductivism in psychiatry? The Italian scenario. PMID- 11787449 TI - How does stress affect you? An overview of stress, immunity, depression and disease. AB - OBJECTIVE: Stress is a term that has become synonymous with modern life. This review aims to appraise the evidence linking stress with disease with particular reference to the major causes of morbidity and mortality in the Western World, cardiovascular disease, cancer, and depression. Changes in immune parameters in stressful situations were reviewed as a possible pathophysiological mechanism for such effects. METHOD: A Medline search was carried out for the period 1996-2000 to identify recent findings in this field using the terms "stress", "disease", "immune system". Relevant references that were found in all identified publications were also followed up. RESULTS: There is evidence to link stress with the onset of major depression and with a poorer prognosis in cardiovascular disease and cancer. Few small studies suggest that stress management strategies may help to improve survival. Chronic stress appears to result in suppression of the immune response, whereas immune activation and suppression have been associated with acute stress. Inflammatory cytokines, soluble mediators of the immune response, can result in symptoms of depression. CONCLUSION: Further prospective epidemiologically based studies are needed to clarify the role of stress on disease onset, course, and prognosis. Stress management strategies, aimed at prolonging survival in patients with cardiovascular disease, cancer, and possibly other chronic illnesses, are an exciting area of further research. Immune system changes may account for the relationship between stress and disease. We propose the "stress, cytokine, depression" model as a biological pathway to explain the link between stressful life events and depression. PMID- 11787450 TI - [For a more rational funding system of mental health services. Analyses of costs for services supplied by community mental health services during a 7-year period]. AB - AIMS: In the last years, in Italy as well as in many other developed countries, there has been a growing interest for health economics by researchers. As for as the psychiatric care is concerned, more recently, many research's groups have pointed their attention on new possible funding systems for mental health services and on their effects on services' functioning. The aim of this study is to define a new list of services' costs based on services actually delivered by a Community Mental Health Service (CMHS). METHODS: All psychiatric contacts recorded by the South-Verona Psychiatric Case Register during a 7-year period (1992-1998) have been included in the study (125,623 contacts made by 2,819 patients). Contacts were grouped into 19 type of services. The cost function methodology was used to describe, also reporting elasticity values, costs' behaviour in the South-Verona CMHS. The cost of each service includes expenses for professionals involved (directly or indirectly) in the contacts with the patients and capital costs. RESULTS: For each service were reported a) the cost of the service as it is actually supplied in our CMHS, b) the cost per minute, c) an estimate of the cost of service delivered with standard modalities (duration equal to the mode value registered; staff composition take into account either the actual functioning of the CMHS either indication about a good clinical practice) and, finally, d) cost of the eight services included into the reimbursement system currently in use in Italy. CONCLUSIONS: Our results showed that services' definition used in this study allow to describe different types of psychiatric care supplied from the South-Verona CMHS. The national list currently adopted for the reimbursement in Italy should allowed to describe only 28% of the registered psychiatric contacts (35,230 vs. 125,632). The urgent need for a new list of psychiatric services, accepted at a national level, was confirmed. Cost values obtained clearly show that the funding system currently used underestimates the true costs of care delivered by the CMHS. The cost function makes available a tool to test a prospective per-capita funding system as provided in the Act No. 229 of the Italian Government. PMID- 11787451 TI - [Suicidal behavior in the North Varese province: a epidemiological analysis]. AB - OBJECTIVE: Analysis of figures and characteristics of suicide behaviour in the area of Varese and the neighbouring northern towns (Valceresio, the valleys around Luino and northern Verbano), with the purpose of finding out preventing measures. DESIGN: Epidemiological-descriptive survey. The 1995-1997 ISTAT death cards, included in the death files of the former USSL of Varese have been taken into consideration. Only those people who were resident at the suicide moment have been included in the survey. Afterwards the psychiatric service archives were consulted, to find any possible contact between the subjects in the ISTAT files and the psychiatric services themselves. With regard to these patients, some information such as suicide attempts, psychiatric pathology and first contact with the psychiatric services have been pointed out. SETTING: Arcisate, Cittiglio, Luino and Varese districts, where the Community Mental Health Services 1 and 2 of "Azienda Ospedaliera Universitaria Macchi" of Varese operate. MAIN OUTCOME MEASURES: The suicide rates in the studied area have been reckoned and, through direct standardization, the rates of the single districts have been compared. RESULTS: There were 78 suicides (24 females and 54 males): rate of 8.2 per 100,000. In accordance with the national trend, there is evidence of a general reduction of the suicide phenomenon, except among the youngest. Districts of Luino and Arcisate are geographic areas to examine in the time, because a wider sample could reveal a higher risk. Young and elderly people are the most affected among the males and, 55/64-year-old people, both males and females, are at higher risk. Suicide methods vary with the age. A high percentage of subjects are not married and with low education. Less than one third of the subjects had come into contact with the psychiatric service. CONCLUSIONS: These data allow a comparison with the national survey and an analysis of the suicide features in the study area. The purpose is to elaborate preventing strategies with multi dimensional approach whose efficacy may be proved in the future by setting up a provincial observatory. PMID- 11787452 TI - [Symptoms and social functioning features in chronic schizophrenia are aggregate in a tripartite structure]. AB - OBJECTIVE: To verify the association between schizophrenic symptoms and multidimensional variables of social functioning and to look for a possible classification based on an empirical classification outcome oriented. DESIGN: Forty chronic schizophrenic patients, with a diagnosis ascertained through clinical interview and diagnostic criteria were enrolled in the study. SETTING: All patients were followed in a State Mental Health center and were assessed in a stabilized phase of illness. PRINCIPAL OUTCOME MEASURES: Psychopathological assessment was made with PANSS and CGI. Psychosocial assessment was made with Life Skills Profile and Global Functioning Scale. RESULTS: A pervasive correlation among symptoms and psychosocial variables emerged suggesting a unitary concept of behavior related to diagnosis. Factor analysis revealed 2 main components able to explain the 79% of variance. Cluster analysis separated the patients in 3 different groups showing that clinical symptoms are aggregated with specific variables of social functioning. CONCLUSION: Schizophrenic symptoms and social functioning are organized in a tripartite structure. It suggests the existence of three different syndromes that are outcome oriented, and compatible with an unitary concept of schizophrenia. PMID- 11787453 TI - [Health of the Nation Outcome Scale (HoNOS)]. PMID- 11787454 TI - [Proceedings of the 10th Anniversary Congress of Surgery. 10-15 October 1998, Sofia]. PMID- 11787455 TI - Abstracts from the ELSO. New Orleans, Louisiana, USA. 16-18 September 2000. PMID- 11787456 TI - Therapeutic Applications of Leukocyte Filtration. Proceedings of a symposium. London, United Kingdom, 7 July 2000. PMID- 11787457 TI - 2nd International Conference on Vaccine Development and Immunotherapy in HIV. San Juan, Puerto Rico, 22-25 May 2001. Abstracts. PMID- 11787458 TI - Clinical guide on treating women with HIV released. PMID- 11787459 TI - Membrane skeleton and its regulatory functions. June 17-20, 2001. Wroclaw, Poland. Abstracts. PMID- 11787460 TI - Proceedings of the VIII National Congress of the Italian Society for Cardiovascular Research. Torino, 20-22 September 2001. PMID- 11787461 TI - A.W. Campbell's Australian career: 1905-1937. AB - The Australian Alfred Walter Campbell (1868-1937) is remembered as one of the two chief pioneers of the study of the cytoarchitectonics of the primate cerebral cortex. He had worked in Britain carrying out neuroanatomical and neuropathological research for almost two decades before his famous monograph on Histological Studies on the Localisation of Cerebral Function appeared in 1905. In that year he returned to his native Australia and practiced for over 30 years in Sydney as a neurologist rather than a neuropathologist, publishing mainly clinical material though he was involved in the investigation of the epidemic of Australian X disease, a viral encephalitis. His abrupt change in both the nature and the location of his career at a time when he was well established in Britain appears to have been a consequence of his marriage and the need to provide for a family. His simultaneous apparent abandonment of research seems not to have really been the case. As judged from the contents of a paper presented to a local medical congress in Sydney in 1911, it appears that, in Australia, Campbell did carry out a major comparative anatomical and histological investigation of the possibility of localization of function in the cerebellar cortex. He never published this work in detail. His investigation let him to conclude that no such localization of function existed, a view contrary to the then topical interpretation of Bolk (1906), but one in accordance with Gordon Holmes' views a decade later. Campbell's circumstances in Sydney, his extremely reticent nature and the essentially negative outcome of his investigation probably explain his failure to make his study more widely known. PMID- 11787462 TI - Thoracoscopic sympathectomy for palmar hyperhidrosis: effects on pulmonary function. AB - Palmar hyperhidrosis, probably caused by an over-reactivity of sympathetic nerves passing through the second and the third thoracic sympathetic ganglia (T2 & T3 ganglia), can only be cured by sympathectomy. Such sympathetic denervation may also alter pulmonary function. Previous studies have shown that open sympathectomy can cause significant deterioration in pulmonary function, however, the surgical procedure itself may contribute to the change. Recently thoracoscopic sympathectomy has been developed as a minimally invasive but effective treatment for palmar hyperhidrosis. In order to investigate the effect of sympathectomy, pulmonary function was compared before and four weeks after operation in 20 patients. Forced vital capacity (FVC) (-2.3%), forced expiratory volume in one second (FEV1) (-6.1%), and FEV1/FVC (-4.6%) were all slightly but significantly decreased four weeks after thoracoscopic sympathectomy. Also the instantaneous forced expiratory flow at 75%, 50% and 25% of the FVC (Vmax25, Vmax50, Vmax75) in flow-volume curves were decreased (-1.6%, -8.4%, and -20% respectively). Therefore, thoracoscopic sympathectomy minimises pulmonary restrictive effects but allows subclinical small airway obstructive effects to become more evident. PMID- 11787463 TI - Trastuzumab: new preparation. May help some patients with breast cancer, but too many unknowns. AB - (1) In the absence of a reference treatment, patients with metastatic breast cancer qualifying for cytotoxic chemotherapy are generally treated with the doxorubicin + cyclophosphamide combination. (2) Trastuzumab, a monoclonal antibody directed against HER2 protein, has been granted marketing authorisation for the treatment of metastatic breast cancer in women with high HER2 protein levels, either as third-line monotherapy, or as first-line combination therapy with paclitaxel. (3) The clinical file only comprises two trials, the results of which are difficult to interpret. (4) In second- or third-line monotherapy, the only available trial (a non comparative study involving 222 patients) gave a median survival time of 13 months. For want of comparative data, there is no way of knowing if the clinical benefit and adverse effects profile of trastuzumab are better than those of other cytotoxic agents. (5) In first- or second-line treatment, there is only one unblinded comparative trial: it compared four groups receiving anthracycline + cyclophosphamide + trastuzumab; anthracycline + cyclophosphamide; paclitaxel + trastuzumab; or paclitaxel alone. The addition of trastuzumab appeared to extend the median survival time by 4-5 months. (6) The main known risks of trastuzumab therapy are cardiac reactions (the most severe) and flu-like syndromes (the most frequent, occurring in 40% of patients). (7) In the two available trials, a retrospective analysis suggested that the impact of trastuzumab was related to the amount of HER2 protein in the tumour. Unfortunately, HER2 assays are poorly standardised. Approximately one-quarter of patients appear to have high tumour HER2 protein contents. (8) At the time of writing (May 2001), the treatment of metastatic breast cancer is not modified by the advent of trastuzumab. PMID- 11787464 TI - [Stomach tumor and increasing abdominal pain after endoscopy]. PMID- 11787465 TI - Stable iodine prophylaxis. PMID- 11787466 TI - Proceedings of the 2nd ESPE Dental Symposium. Philadelphia, Pennsylvania, USA. May 5-6, 2000. PMID- 11787467 TI - Positive inotropic responses mediated by endothelin ET(A) and ET(B) receptors in human myocardial trabeculae. AB - The aim of the present study was to determine possible inotropic effects mediated by endothelin ET(A) and ET(B) receptors in human myocardial trabeculae from the right atrium and the left ventricle. Isolated trabeculae from human hearts were paced at 1.0 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Endothelin-1 (ET-1) and ET-3 had a strong positive inotropic effect in all trabeculae. ET-1 was significantly more potent than ET-3 in both atrial (P < 0.001) and ventricular (P < 0.05) trabeculae. Preincubation with the ET(A) receptor antagonist FR139317 (1 microM) decreased significantly (P < 0.005) the potency of ET- I in both atrial and ventricular trabeculae, without any significant changes in Emax (maximum effect obtained with an agonist). The ET(B) receptor agonist IRL 1620 had a positive inotropic effect only in some trabeculae, and the ET(B) receptor antagonist BQ 788 (1 microM) almost completely blocked this effect. These results suggest that both ET(A) and ET(B) receptors mediate positive inotropic responses at both the atrial and ventricular level in the human heart. PMID- 11787468 TI - Vasoconstriction to endogenous endothelin-1 is impaired in patients with type II diabetes mellitus. AB - Endothelin-1 has potent vasoconstrictor and vasopressor actions contributing to basal vascular tone and maintenance of blood pressure acting predominantly through endothelin-A receptors. Endothelin antagonists may be of value in the treatment of hypertension and heart failure. However, the role of endothelin-1 in the regulation of vascular tone and the potential benefits of endothelin antagonists in non-insulin-dependent diabetes mellitus (Type II diabetes) are less clear. Vasoconstriction to exogenous endothelin-1 is impaired in Type II diabetes. The purpose of this study was to determine whether vasoconstriction to endogenous endothelin-1 acting through the endothelin-A receptor is impaired in Type II diabetes. In ten patients with Type II diabetes and nine controls the endothelin-A receptor antagonist BQ123 was infused intra-arterially at 100 nmol/min for 60 min followed by normal saline for 30 min. Forearm blood flow was measured using venous occlusion plethysmography. Control subjects showed gradual onset of vasodilation in response to BQ123 (P < 0.001). Diabetic subjects, however, showed no significant response (P > 0.05). There was a significant difference between the diabetic and control groups (P < 0.05). Blockade of the endothelin-A receptor is associated with impaired vasodilation in Type II diabetes indicating vasoconstriction to endogenous endothelin-1 mediated by the endothelin-A receptor is impaired. PMID- 11787469 TI - Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle. AB - There is evidence that burn injury stimulates ubiquitin-proteasome-dependent protein breakdown in skeletal muscle. In this proteolytic pathway, protein substrates are conjugated to multiple molecules of ubiquitin, whereafter they are recognized, unfolded and degraded by the multicatalytic 26 S protease complex. The 20 S proteasome is the catalytic core of the 26 S protease complex. The influence of burn injury on the expression and activity of the 20 S proteasome has not been reported. We tested the hypothesis that burn injury increases 20 S proteasome activity and the expression of mRNA for the 20 S proteasome subunits RC3 and RC7. Proteolytic activity of isolated 20 S proteasomes, assessed as activity against fluorogenic peptide substrates, was increased in extensor digitorum longus muscles from burned rats. Northern-blot analysis revealed that the expression of mRNA for RC3 and RC7 was increased by 100% and 80% respectively following burn injury. Increased activity and expression of the 20 S proteasome in muscles from burned rats support the concept that burn-induced muscle cachexia is at least, in part, regulated by the ubiquitin-proteasome proteolytic pathway. PMID- 11787470 TI - Inhibition of muscle glutamine formation in hypercatabolic patients. AB - Glutamine is synthesized primarily in skeletal muscle, and enables transfer of nitrogen to the liver, as well as serving other functions. There is increasing evidence for beneficial clinical effects of glutamine supplementation in critically ill patients. However, the response of endogenous glutamine formation to severe stress is poorly understood. The rates of net protein balance, leucine oxidative decarboxylation, and alanine and glutamine synthesis de novo were determined in leg skeletal muscle of 20 severely burned patients and 19 normal controls in the post-absorptive state. Patients were studied at 14+/-5 days post burn, and their mean burn size was 66+/-18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle. In the post-absorptive state, patients with severe burns, as compared with healthy control subjects, exhibited accelerated muscle loss (+150%) (i.e. proteolysis minus synthesis) and leucine oxidative decarboxylation (+117%), and depletion of the intramuscular free glutamine pool (-63%). The average rate of glutamine synthesis de novo was decreased by 48%, whereas net alanine synthesis de novo was increased by 174%, in skeletal muscle of burned patients. In conclusion, in severely hypercatabolic burned patients, muscle glutamine formation was suppressed, whereas alanine was the major vehicle for inter-organ nitrogen transport. These changes account for a decreased glutamine availability during prolonged severe stress. PMID- 11787471 TI - Renal synthesis of dopamine in asymptomatic post-infarction left ventricular systolic dysfunction. AB - Left ventricular systolic dysfunction (LVSD) following acute myocardial infarction (AMI), by decreasing renal blood flow, may interfere with renal L-DOPA availability and, consequently, dopamine synthesis. Dopamine of renal origin exerts local natriuretic effects. We studied 17 post-AMI patients with asymptomatic LVSD (ejection fraction < 40%) and 14 without (ejection fraction > or = 40%), measuring 24-h urinary excretions of L-DOPA, dopamine and its metabolites, and plasma levels of the amines, amine derivatives and type-B natriuretic peptide (BNP). Baseline characteristics were well balanced between the two groups. No differences were observed in urinary volume and sodium and creatinine excretions. The group with asymptomatic LVSD presented lower urinary excretion of L-DOPA (66.8 +/- 10.1 versus 115.3 +/- 21.9 nmol x day(-1), P = 0.04), whereas plasma levels of L-DOPA were identical in both groups. Urinary dopamine was similar in the two groups (1124.2 +/- 172.4 versus 1049.0 +/- 146.4 nmol x day(-1), P = 0.86), resulting in higher urinary dopamine/L-DOPA ratios in patients with asymptomatic LVSD (20.4 +/- 3.0 versus 9.9 +/- 0.8, P < 0.001). Plasma levels of BNP were higher in the asymptomatic LVSD group (348.5 +/- 47.3 versus 146.8 +/- 21.9 microg x ml(-1), P = 0.003). Ejection fraction was negatively correlated with both plasma levels of BNP and urinary dopamine/L-DOPA ratios. Renal dopamine production is well preserved in patients with asymptomatic LVSD and increased neurohumoral activation, despite reduced urinary excretion of its precursor. This suggests that renal uptake and/or decarboxylation of L-DOPA is enhanced in this condition, as a compensatory mechanism, contributing to preservation of urinary sodium excretion. PMID- 11787473 TI - Thrombopoietin levels in serum and liver tissue in patients with chronic viral hepatitis and hepatocellular carcinoma. AB - Thrombocytopenia in liver diseases is considered to be due to splenic platelet pooling and accelerated destruction. Since thrombopoietin (TPO), a regulator of thrombopoiesis, is produced mainly in the liver, decreased production of TPO may account for thrombocytopenia in liver diseases. To address this issue, we measured serum TPO, using a sensitive sandwich ELISA, in 108 patients with chronic viral hepatitis, which included chronic hepatitis (CH) and liver cirrhosis (LC), and hepatocellular carcinoma (HCC), and in 29 normal controls. TPO mRNA in 78 liver samples was examined by reverse transcription (RT)-PCR. Platelet counts in CH, LC, HCC and controls were 176 +/- 15 x 10(9)/l, 81 +/- 8 x 10(9)/l, 99 +/- 7 x 10(9)/l and 234 +/- 9 x 10(9)/l respectively. Serum TPO levels in CH, LC and HCC were 2.79 +/- 0.4 fmol/ml, 1.49 +/- 0.2 fmol/ml and 1.97 +/- 0.2 fmol/ml, and were higher than those of controls. Serum TPO levels were positively correlated with prothrombin time and serum albumin (P < 0.05, in each case), and negatively correlated with Indocyanine Green test and Pugh score (P < 0.01 and P < 0.05 respectively). However, RT-PCR and immunohistochemistry showed that expression of TPO mRNA and protein were similar in the different liver diseases, suggesting that serum TPO is a reflection of the total mass of functional liver. Platelet counts were negatively correlated with spleen index, but not with serum TPO. These results suggest that thrombocytopenia in liver disease is not directly associated with serum TPO but is associated with hypersplenism. PMID- 11787472 TI - Vasoactive intestinal peptide down-regulates the intrahepatic renin-angiotensin system in the anaesthetized rat. AB - Gastric sodium loading results in an increase in the portal venous concentration of vasoactive intestinal peptide (VIP) and down-regulation of both the intrahepatic and circulating renin-angiotensin systems. In the present study we sought to determine whether an increase in the concentration of VIP in the portal circulation might act to down-regulate the intrahepatic and/or circulating renin angiotensin systems. Male Sprague-Dawley rats were infused intraportally with haemaccel vehicle or VIP in haemaccel for 60 min. Livers were harvested and blood was sampled. Angiotensin-converting enzyme (ACE) activity and angiotensinogen, angiotensin I, angiotensin II and renin concentrations were measured. VIP infusion decreased hepatic ACE activity (P < 0.05), the hepatic angiotensinogen concentration (P < 0.001) and the hepatic angiotensin I concentration (P < 0.05). The plasma angiotensinogen concentration and serum ACE activity were also decreased by intraportal VIP infusion (P < 0.05 for each). Plasma renin, angiotensin I and angiotensin II concentrations were unchanged by VIP infusion. We conclude that an increase in the portal venous VIP concentration down regulates the intrahepatic renin-angiotensin system. These changes are similar to those reported after gastric sodium loading, and we suggest, therefore, that the increase in portal venous VIP that occurs after gastric sodium is the means by which the gastric sodium sensor signals the liver to effect these changes in the renin-angiotensin system. PMID- 11787474 TI - Use of anti-(tumour necrosis factor-alpha) antibody or 3-deaza-adenosine as additives to promote protection by University of Wisconsin solution in ischaemia/reperfusion injury. AB - Experimental interventions that reduce ischaemia/reperfusion (I/R) lung injury can be used to improve the properties of preservation solutions. We attempted to increase the attenuation of I/R injury by University of Wisconsin solution (UW) by adding an antibody against tumour necrosis factor-alpha (TNF-alpha), to neutralize TNF-alpha, and/or by adding 3-deaza-adenosine (c3-Ado), to inhibit leucocyte adhesion and the biosynthesis of ICAM-1 (intercellular cell-adhesion molecule 1). We examined I/R injury using an isolated rat lung model. Six different solutions were perfused individually, followed by evaluation of I/R injury: (1) 0.9% NaCl (normal saline; NS), (2) NS+anti-TNF-alpha antibody, (3) UW alone, (4) UW+anti-TNF-alpha, (5) UW+c3-Ado and (6) UW+anti-TNF-alpha+c3-Ado. Haemodynamic changes, lung weight gain, capillary filtration coefficient, TNF alpha levels and lung pathology were analysed in order to evaluate I/R injury. Compared with lungs perfused with NS, lungs treated with NS+anti-TNF-alpha showed less I/R injury. The addition of anti-TNF-alpha and/or c3-Ado to UW reduced I/R injury compared with unmodified UW. Among the six solutions tested, UW containing anti-TNF-alpha antibody reduced I/R injury to the greatest extent. We conclude that addition of anti-TNF-alpha antibody or c3-Ado protects against I/R lung injury when using UW. Further investigation of the improved properties of modified UWs would be beneficial with regard to lung transplantation research. PMID- 11787475 TI - Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans. AB - Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829-1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P < 0.01), mean arterial pressure (P < 0.01), and blood glycerol concentration (P < 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea. PMID- 11787476 TI - Pharmacogenomics of hypertension: a realizable goal? PMID- 11787477 TI - The gain-of-function G389R variant of the beta1-adrenoceptor does not influence blood pressure or heart rate response to beta-blockade in hypertensive subjects. AB - Mutation scanning of the beta1-adrenoceptor gene has identified a polymorphism, G389R, that markedly affects G-protein coupling of the receptor and resulting cAMP production. We have investigated the effect of this functionally active polymorphism on clinical response to beta-adrenoceptor blockade. Two cohorts of untreated hypertensive patients randomly assigned to a beta1-selective beta blocker at the start of antihypertensive therapy were studied retrospectively to see if the G389R polymorphism influenced the response in terms of blood pressure and heart rate. The blood pressure and heart rate responses to treatment were assessed 4 weeks later and compared with the G389R genotype, ascertained by PCR/restriction fragment length polymorphism. The falls in blood pressure and heart rate for the first group (n = 92) by genotype were: GG, 20.1 +/- 3.5/13.9 +/- 2.7 mmHg (systolic/diastolic blood pressure), 18.4 +/- 2.2 beats/min; GR, 20.0 +/- 2.2/15.0 +/- 1.3 mmHg, 16.5 +/- 1.5 beats/min; RR, 20.8 +/- 2.3/13.4 +/- 1.1 mmHg, 16.0 +/- 1.4 beats/min. For the second group (n = 55) the corresponding falls were: GG, 17.0 +/- 4.3/11.2 +/- 3.4 mmHg, 12.0 +/- 3.5 beats/min; GR, 16.6 +/- 1.8/14.4 +/- 1.1 mmHg, 13.1 +/- 2.1 beats/min; RR, 18.0 +/- 1.6/13.0 +/- 1.4 mmHg, 14.4 +/- 1.4 beats/min. The G389R genotype also failed to have a significant effect on pretreatment blood pressure or heart rate in either group. These data suggest that, despite clear functional differences between the G389R receptor variants expressed in vitro, the polymorphism does not affect the haemodynamic response of hypertensive subjects to chronic beta1-adrenoceptor blockade. PMID- 11787478 TI - T-ceIl recognition of discrete regions of the thrombolytic drug streptokinase. AB - Streptokinase (SK) is a bacterial protein used clinically as a thrombolytic agent in humans. Administration of SK causes a rapid increase in the frequency of anti SK T cells and the titre of specific anti-SK antibodies that, on subsequent administration of SK, may neutralize the activity of the drug or elicit allergic type reactions. By locating and modifying the immunogenic T-cell epitopes within the SK protein, it is possible that an agent with reduced immunogenicity but equal efficacy may be produced. We have investigated the T-cell epitopes within SK using nine non-overlapping, recombinant peptide fragments of SK. We investigated the proliferative T-cell response of peripheral blood mononuclear cells obtained from patients before and 6 days after administration of SK for myocardial infarction. We also examined the response of cultured anti-SK T-cell lines derived from patients 6 days after treatment with SK. Before administration of SK, peripheral blood mononuclear cells from six of nine patients showed a proliferative response to SK. The response was significantly higher 6 days after administration of SK (P = 0.0004). Cultured T-cell lines showed similar proliferative responses to clinical-grade SK and recombinant SK. Marked differences in T-cell responses were apparent in response to each recombinant SK fragment (P = 0.04). The mean proliferative response exceeded background to only two peptides, peptide 2 (P = 0.04) and peptide 3 (P = 0.009). Peptide 3, representing amino acids 100-150 of mature SK, was recognized preferentially in the majority of assays. Marked variation in the T-cell response to SK following treatment with this agent was observed between subjects. Despite these differences, peptides 2 and 3 induced T-cell proliferation at a level significantly above background in the majority of subjects. These epitopes may represent a region of enhanced immunogenicity within SK. PMID- 11787480 TI - Substance dependence in elderly people. PMID- 11787479 TI - Angiotensin-converting enzyme gene polymorphism and premature coronary heart disease. AB - Since the initial report of the association of the deletion/insertion (D/I) polymorphism in the gene for angiotensin-converting enzyme (ACE) with myocardial infarction (MI), there has been considerable controversy. Some have found the D allele to be associated with MI, coronary heart disease (CHD) or other cardiac pathology, while others have not. In the present study 713 consecutive patients, < 50 years of age, documented prospectively with angiographic CHD (> 50% diameter stenosis of at least one coronary artery), with or without MI, were studied, along with 688 community control subjects, also < 50 years of age, selected randomly from the electoral rolls and without a history of CHD or MI. Genotyping was done by standard methods. Most of the subjects in both groups were Anglo Celtic Caucasians (547 in the CHD group and 642 in the community group), and the report concerns primarily these subjects. ACE genotype distributions were not different between the Caucasian community control group and the CHD or the MI subgroups; the odds ratios and 95% confidence limits for the CHD group were 0.96 (0.73-1.27) for the D allele and 1.02 (0.80-1.31) for D homozygotes; for the MI group these values were 1.00 (0.83-1.20) and 0.99 (0.74-1.32) respectively. This negative result was supported in multivariate analysis accounting for conventional risk factors. There was a significant racial difference in ACE genotypes between Caucasians, Asians and Australian Aborigines in the CHD group (P < 0.001); for example, in this group, 158 of 540 (29%) Caucasians had the DD genotype compared with eight of 84 (10%) Aboriginals (P < 0.001) and six of 59 (10%) Asians (P = 0.002). Failure to account for such racial differences would have led to erroneous conclusions. In conclusion, we found no evidence that the D/I ACE gene polymorphism plays a role in the development of CHD or MI at an early age in a Western Australian Caucasian population. While this result refers uniquely to premature CHD and MI, and could be population specific, it is in general agreement with recent meta-analysis of the larger previous studies. PMID- 11787481 TI - From the Centers for Disease Control and Prevention. Update: adverse events associated with anthrax prophylaxis among postal employees--New Jersey, New York City, and the District of Columbia metropolitan area, 2001. PMID- 11787482 TI - From the Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related inhalation anthrax--Connecticut, 2001. PMID- 11787483 TI - From the Centers for Disease Control and Prevention. Imported wild poliovirus causing poliomyelitis--Bulgaria, 2001. PMID- 11787484 TI - JAMA patient page. Seasonal allergic rhinitis. PMID- 11787485 TI - Proceedings of the 3rd Multi-Disciplinary International Symposium on Supraesophageal Complications of Reflux Disease. August 10-12, 2000. Boston, Massachusetts, USA. PMID- 11787486 TI - From Epidemiology to Policy. Proceedings of a symposium on the translation on epidemiologic evidence into public health policy. July 27-29, 1998. Washington, DC, USA. PMID- 11787487 TI - [Sensitivity of four representative angular cephalometric measures]. AB - OBJECTIVE: Examined the sensitivity of four representative cephalometric angles to the detection of different vectors of craniofacial growth. METHODS: Landmark coordinate data from a stratified random sample of 48 adolescent subjects were used to calculate conventional values for changes between the pretreatment and end-of-treatment lateral cephalograms. By modifying the end-of-treatment coordinate values appropriately, the angular changes could be recalculated reflecting three hypothetical situations: Case 1. What if there were no downward landmark displacement between timepoints? Case 2. What if there were no forward landmark displacement between timepoints? Case 3. What if there were no Nasion change? These questions were asked for four representative cephalometric angles: SNA, ANB, NAPg and UI-SN. RESULTS: For Case 1, the associations (r) between the baseline and the modified measure for the three angles were very highly significant (P < 0.001) with r2 values no lower than 0.94! For Case 2, however, the associations were much weaker and no r value reached significance. CONCLUSIONS: These angular measurements are less sensitive for measuring downward landmark displacement than they are for measuring forward landmark displacement. PMID- 11787488 TI - From the Centers for Disease Control and Prevention. Coccidioidomycosis in workers at an archeologic site--Dinosaur National Monument, Utah, June-July 2001. PMID- 11787489 TI - From the Centers for Disease Control and Prevention. Childhood vaccines--United States, 1995-1999. PMID- 11787490 TI - JAMA patient page. Adolescent suicide. PMID- 11787491 TI - Abstracts of the 22nd annual meeting of the Society for Maternal-Fetal Medicine. January 14-19, 2002. New Orleans, Louisiana, USA. PMID- 11787492 TI - Guidelines for head injury: their use and limitations. AB - Within medicine in general, and particularly in the field of head injury, a revolution is currently occurring wherein the traditional expert opinion-based approach to therapy is quickly changing towards a standardized approach, based on scientific analysis of available evidence. The guideline movement may be considered a child of this revolution. Correct understanding, interpretation and application of guidelines requires an understanding of the reasons for formulating the guidelines and of the methodology on which they are based. From this perspective the North American guidelines and the EBIC guidelines, as main international exponents towards guidelines in head injury, are discussed. Specific attention is focussed on the interpretation of the practice recommendations from the North American guidelines at the level of a standard. The evidence underlying these standards is critically discussed and the conclusions put in to further perspective. The EBIC guidelines were formulated from a desire to obtain a 'common core approach' to basic therapy in centers participating in clinical trials. The recommendations are more pragmatic, based on an understanding of the pathophysiology, and address various issues not analyzed in the North American guidelines. The recommendations of both initiatives however are very similar, illustrating the consensus that already exists to general approach of management in head injury. Guidelines should be considered a very important topic in clinical practice, but on the other hand recommendations should not always be accepted uncritically. The lack of evidence underlying many aspects of management in head injury, as illustrated by the North American approach, should form an incentive for further scientific studies, especially towards targeted therapy. Clinical experience and an understanding of the pathophysiology are the basic ingredients for developing alternative and more targeted approaches which can then be subjected to scientific analysis. Guidelines should be considered a tool which we need to learn how to use; they form part of a process which, following implementation and dissemination should lead to standardized registration, an important element in facilitating improved quality control and assurance. PMID- 11787493 TI - Reverse micellar extraction for downstream processing of proteins/enzymes. AB - New developments in the area of downstream processing are, hopefully, to fulfill the promises of modern biotechnology. The traditional separation processes such as chromatography or electrophoresis can become prohibitively expensive unless the product is of high value. Hence, there is a need to develop efficient and cost-effective downstream processing methods. Reverse micellar extraction is one such potential and a promising liquid-liquid extraction technique, which has received immense attention for isolation and purification of proteins/enzymes in the recent times. This technique is easy to scale-up and offers continuous operation. This review, besides briefly considering important physico-chemical and biological aspects, highlights the engineering aspects including mass transfer, mathematical modeling, and technology development. It also discusses recent developments in reverse micellar extraction such as affinity based separations, enzymatic reactions in reverse micelles coupled with membrane processes, reverse micellar extraction in hollow fibers, etc. Special emphasis has been given to some recent applications of this technique. PMID- 11787494 TI - Abstracts of the IXth International Symposium on Amyloidosis. Budapest, Hungary, July 15-21, 2001. PMID- 11787495 TI - Abstracts of the European Congress on Menopause. 1-5 July 2000. PMID- 11787496 TI - IPK'2001. Abstracts of the 2nd International Conference on Inhibitors of Protein Kinases and the Workshop on Computer-Aided Drug Design. September 9-15, 2001. Warsaw, Poland. PMID- 11787497 TI - When expertise and ethics diverge: lay and professional evaluation of psychotherapists in Israel. AB - Do psychotherapists' unethical practices influence how they are perceived? The 202 Israeli lay and professional psychology participants rated systematically varied descriptions of effective therapists and potential clients under conditions of no difficulties (standard), practice without a license, and a previous sexual boundary violation on indexes of evaluation and willingness to refer. Participants completed a measure of important variables in therapist selection. Effective standard therapists were rated most favorably, unlicensed therapists were rated favorably, and therapists who violated sexual boundaries in the past were rated least favorably. When results were analyzed by respondent characteristics, laypersons rated unlicensed professionals (p < .01) and sexual boundary violators (p < .0001) more positively than did clinical psychologists. Men rated the violators more favorably than did women (p < .05). Factor analysis of therapist selection measures identified professional and personal factors, but only the former were associated with ratings of "problem" therapists. The results underscore the gap between ethical standards and applied decisions made by professionals and laypersons. Further investigation is needed to ensure quality care in both professional and consumer approaches to psychotherapy. PMID- 11787498 TI - Managed health care in prisons as cruel and unusual punishment. PMID- 11787499 TI - Docile bodies? Chemical restraints and the female inmate. PMID- 11787500 TI - Maternal duties toward the unborn? Soundings from the law of tort. PMID- 11787501 TI - Breach of confidence: anonymised information. R. v. Department of Health ex parte Source Informatics Ltd. PMID- 11787502 TI - Incompetent patient (child): HIV testing and best interest. Re C (HIV test). PMID- 11787503 TI - Withdrawal of life sustaining treatment for child without parental consent. R. v. Portsmouth Hospitals N.H.S. Trust ex parte Glass. PMID- 11787504 TI - Letter to President Bush on federal funding for embryonic stem cell research. PMID- 11787505 TI - Toward a feminist theory of disability. AB - We need a feminist theory of disability, both because 16 percent of women are disabled, and because the oppression of disabled people is closely linked to the cultural oppression of the body. Disability is not a biological given; like gender, it is socially constructed from biological reality. Our culture idealizes the body and demands that we control it. Thus, although most people will be disabled at some time in their lives, the disabled are made "the other," who symbolize failure of control and the threat of pain, limitation, dependency, and death. If disabled people and their knowledge were fully integrated into society, everyone's relation to her/his real body would be liberated. PMID- 11787506 TI - Assisted reproduction and the frustration of genetic affinity: interest, injury, and damages. PMID- 11787507 TI - Archived specimens: a platform for discussion. AB - To facilitate discussion, this paper describes various types of collections of specimens, their uses in research, types of identifiers, requirements for informed consent, third-party access to samples, recontact, and controversial ethical and social issues. There is need for public opinion research on people's views of these issues, with particular attention to the views of minority groups. PMID- 11787508 TI - Transsexualism in medicolegal limine: an examination and a proposal for change. AB - This article investigates transsexualism and our creation of a state of medicolegal limine for transsexuals. The article addresses transsexuality as it is currently defined and explores our dichotomization of sex and gender. The author discusses both the social construction and the praxis of transsexuality, highlighting the medicolegal implications resulting from our current approach to transsexuality. The author argues that the creation of a medicolegal limine essentially prevents transsexuals from ever integrating fully as a member of one sex or gender, while simultaneously preventing the larger society from reconsidering its definitions of sex and gender. The article concludes with a summary of current challenges to our model of transsexualism and with suggestions for the resolution of this liminal medicolegal phase. PMID- 11787509 TI - The export of hazardous products and industries: a bibliography. PMID- 11787510 TI - Age variations in personal agency and self-esteem: the context of physical disability. AB - OBJECTIVES: This study examines how age patterns in health control, self efficacy, and self-esteem are influenced by age-correlated social status, health, personality, and social integration variables. METHODS: Ordinary least squares regression documents age patterns in data from a 1985 community sample of 1,549 physically disabled and nondisabled individuals from southwestern Ontario, Canada. RESULTS: Older respondents report lower health control, self-efficacy, and self-esteem. Less education, more physical impairment, poorer global health, less empathy, and less introspectiveness explain about 43% of age's negative association with health control and more than half of its negative association with self-esteem. In addition, age is associated more negatively with self efficacy among the disabled. Social status variables conceal the strength of the age-by-disability interaction coefficient, while health accounts for almost an equal amount. DISCUSSION: The findings describe how age-correlated personal and social factors contribute to, or statistically conceal, older adults' sense of health control, self-efficacy, and self-esteem. PMID- 11787511 TI - The effect of widowhood on weight change, dietary intake, and eating behavior in the elderly population. AB - OBJECTIVES: To assess the effect of recent widowhood on weight, dietary intake, and habits. METHODS: Participants included 58 recently widowed elderly subjects and 58 married subjects who were matched on age, sex, and race. Weight change from baseline and following widowhood, dietary intake, eating behavior, depression, and cognitive and physical functioning were assessed in a clinic interview. RESULTS: Mean weight loss and the prevalence of weight loss were significantly higher among widowed participants. They ate more meals alone, more commercial meals per week, and fewer snacks and homemade meals. They also enjoyed their eating less. A significant difference between cases and controls was evident after adjusting for all the variables. Higher cognitive functioning score, younger age, and better appetite were protective against weight loss. DISCUSSION: Widowed people were found to be at increased risk for weight loss. This may well be due to decreased appetite and enjoyment of their meals. PMID- 11787512 TI - Appraisal of 4 months' consumption of nutrient-dense foods within the daily feeding pattern of frail elderly. AB - OBJECTIVES: The appraisal and acceptance of micronutrient-dense versus identical regular foods among frail elderly are described. METHODS: Four types of dairy and four types of fruit products, either enriched with multiple micronutrients or not, were consumed by 150 frail elders for 4 months. In the first 2 and last 2 weeks of the intervention, hedonic aspects were assessed. Afterward, evaluation forms were completed. RESULTS: At the start, small but consistent differences existed between the enriched and the regular foods concerning the scores on pleasantness, desire to eat the product, and attitude toward the product. At the end, those ratings dropped slightly or stayed equal. Significant differences between groups emerged from the overall evaluation score: 6.4 plus or minus 1.6 and 7.7 plus or minus 1.7 respectively (p <.001). DISCUSSION: Optimization of the hedonic parameters of nutrient-dense foods and major long-term attention for application in the daily elderly feeding pattern is of essential importance. PMID- 11787513 TI - Residential care supply and cognitive and physical problem case mix in nursing homes. AB - OBJECTIVES: A rapid evolution has occurred in state policy and industry practices relative to assisted living and expanded use of residential care facilities for people with physical and cognitive frailty, yet relatively little is known about the interrelationship between this housing supply and nursing-home case mix. METHODS: The association between residential care supply and the proportion of cognitively and physically impaired nursing facility residents was examined in more than 1,500 facilities in five states. RESULTS: The proportion of nursing home cases with only physical and cognitive impairment likely to be affected by emerging long-term care policy appears to be well under 10%. This effect is more persistent among admissions than continuing cases. DISCUSSION: The findings raise caution about the optimistic assumptions of the interplay between residential care/assisted living policy and nursing-home use. PMID- 11787514 TI - The relationship between subjective and objective memory in the oldest old: comparisons of findings from a representative and a convenience sample. AB - OBJECTIVES: To evaluate the hypotheses that subjective memory ratings are more accurate in the oldest old than in the young old and more accurate in a representative sample than in a convenience sample. METHODS: Outcomes of hierarchical regressions of subjective ratings and participant characteristics on recall were compared between a nationally representative sample of 6,446 adults ages 70 to 103 and a convenience sample of 326 adults ages 70 to 97. RESULTS: Education interacted with memory ratings in the prediction of performance in the representative sample, with better prediction for more highly educated participants than for participants with lower levels of education. DISCUSSION: The general pattern of findings was consistent across both samples and neither hypothesis was supported. Possible explanations for the similarity of results across samples are considered. PMID- 11787515 TI - Tiredness as determinant of subsequent use of health and social services among nondisabled elderly people. AB - OBJECTIVE: To examine whether self-reported tiredness in daily activities at age 75 is an independent determinant of incident hospitalization and use of home services 5 years later. METHODS: In all, 275 people participated in a prospective study in Glostrup, Denmark, when they were 75 and 80 years old. Four subgroups were created according to whether participants had been hospitalized or used home care in the year before the baseline study and whether or not they were disabled at the time. The key predictor variables were measured by two scales about tiredness in daily activities. RESULTS: Nondisabled individuals who felt tired in their daily activities had about twice the risk of being hospitalized and of being users of home help 5 years later. CONCLUSIONS: Because tiredness in daily activities is related to subsequent hospitalization and use of home help, it should be taken seriously in preventive services among elderly people. PMID- 11787516 TI - A prediction model of aerobic exercise in older adults living in a continuing care retirement community. AB - OBJECTIVES: The purpose of this study was to test a model of exercise behavior in older adults. It was hypothesized that gender, marital status, chronic illness, mental and physical health, self-efficacy and outcome expectations, fear of falling, and past exercise behavior were directly and/or indirectly associated with current exercise behavior. METHODS: In this descriptive study, interviews were conducted with 201 older adults living in a continuing-care retirement community. RESULTS: Twelve paths were significant, and the model accounted for 40% of the variance in exercise behavior. Self-efficacy expectations, outcome expectations, and prior exercise were directly associated with current exercise; health status, gender, and marital status were indirectly associated with current exercise behavior through self-efficacy and outcome expectations. DISCUSSION: Recognizing and treating mental and physical health problems may directly influence self-efficacy and outcome expectations related to exercise. Moreover, interventions that strengthen self-efficacy and outcome expectations related to exercise may improve exercise behavior. PMID- 11787517 TI - New challenges for organ transplantation. PMID- 11787518 TI - AIDS, public health and the law: a case of structural coupling? PMID- 11787519 TI - Effect of CMW 1 bone cement on transforming growth factor-beta 1 expression by endothelial cells. AB - The present study examined the effects of in vitro challenge with an acrylic bone cement CMW 1 on the expression of transforming growth factor-beta 1 (TGF-beta 1) in human umbilical vein endothelial cells (HUVEC). The extracts in cell culture medium of the cements were tested, after 1 h and 7-day curing. Some cultures were also stimulated with interleukin-1 beta (IL-1 beta) or all-trans retinoic acid (ATRA). The expression of mRNA was evaluated by RT-PCR with specific primers. The release of TGF-beta 1 into the conditioned medium was evaluated by enzyme immunoassay. TGF-beta 1 mRNA was constitutively expressed by endothelial cells in the culture medium after 24 h. The incubation with the extracts of CMW 1, cured both for 1 h and 7 days, induced changes neither in mRNA expression, nor in the release of TGF-beta 1 into the conditioned medium, compared to the unstimulated cells. Even stimulation with ATRA, alone or added to the extracts at both curing times, affected neither mRNA expression nor TGF-beta 1 release, compared to the cells incubated with the cement alone or with the unstimulated cultures. The mRNA expression and the release were not changed by the stimulation with IL-1beta alone or added to the extract cured for 1 h. A significant decrease compared to the unstimulated cells was observed after the addition of IL-1 beta to the extract cured for 7 days. It was concluded that CMW 1 extract did not significantly modify TGF-beta 1 expression after 1-h curing, or after 7-day curing. Incubation with CMW 1 added with ATRA did not produce any changes in TGF beta 1 synthesis. Incubation with cement extract after 7-day curing added with IL beta 1 produced a significant reduction in TGF-beta 1 release. PMID- 11787520 TI - Immobilization of papain on cold-plasma functionalized polyethylene and glass surfaces. AB - Polyethylene and glass surfaces were functionalized under dichlorosilane-RF-cold plasma environments and were employed as substrates for further in situ derivatization reactions and immobilization of papain. Surface functionality changes of RF-plasma-exposed surfaces were monitored under 40 kHz continuous discharge environments. The nature and morphology of derivatized substrates and the substrates bearing the immobilized enzyme were analyzed using survey and high resolution ESCA, ATR-FTIR, and fluorescence of chemical derivatization techniques. Spacer molecules intercalated between the substrates and the enzyme significantly increased the enzyme activity (comparable with the that of the free enzyme). Computer-aided conformational modeling of the substrate-spacer systems corroborated with experimental data indicated that an optimal distance might exist between the enzyme and the substrate. The activity of free and immobilized papain was monitored using benzoyl arginine ethyl ester assay. The pH data were recorded every 0.3 s over 25 min. The Michaelis-Menten kinetic constants were evaluated for immobilized enzymes. It was shown, that the immobilized papain retains most of its activity after several washing/assay cycles. PMID- 11787521 TI - Determination of pore diameter and molecular weight cut-off of hydrogel-membrane liquid-core capsules for immunoisolation. AB - The exclusion limit expressed as the largest pore size of capsules composed of hydrogel Ca-alginate membrane and hydroxy-propyl-ammonium starch liquid core considered as the immunoprotective system has been determined by means of inverse size exclusion chromatography with dextran molecular weight standards. The exclusion limits of the capsules were not influenced by the change of starch concentration in the core solution from 4 to 6% but were influenced by the change in alginate concentration in the membrane from 0.5 to 1.0%, causing the membranes to be less permeable. It was found that the diameter of the largest pores in hydrogel membranes was in the range 7.2-8.0 nm. Based on the relationship between solute size and its molecular weight, the capsules had an approximate exclusion limit of 21-25 kD for dextran and 78-103 kD for protein, which is sufficient to block the antibodies penetrating through the membrane. PMID- 11787522 TI - A vanadium/aspirin complex controlled release using a poly(beta-propiolactone) film. Effects on osteosarcoma cells. AB - A delivery system for vanadium was developed using poly(beta-propiolactone) (PbetaPL) films. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with films prepared from polymers of different molecular weights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the PbetaPL film. The experimental data at an early stage of release were fitted with a diffusion model, which allowed determination of the diffusion coefficient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coefficient (approximately 10(-2)). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the PbetaPPL film. VOAspi-PbetaPL film inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation. compared to that with free VOAspi in solution. The unloaded PbetaPL film did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi-PbetaPL films suggest that this delivery system may have promising biomedical and therapeutic applications. PMID- 11787523 TI - Inhibition of monocyte adhesion and fibrinogen adsorption on glow discharge plasma deposited tetraethylene glycol dimethyl ether. AB - Monocytes and macrophages play important roles in host responses to implanted biomedical devices. Monocyte and macrophage interactions with biomaterial surfaces are thought to be mediated by adsorbed adhesive proteins such as fibrinogen and fibronectin. Non-fouling surfaces that minimize protein adsorption may therefore minimize monocyte adhesion, activation, and the foreign body response. Radio-frequency glow discharge plasma deposition (RF-GDPD) of tetraethylene glycol dimethyl ether (tetraglyme) was used to produce polyethylene oxide (PEO)-like coatings on a fluorinated ethylene-propylene (FEP) surface. Electron spectroscopy for chemical analysis (ESCA) and static time of flight secondary ion mass spectrometry (ToF-SIMS) were used to characterize the surface chemistry of tetraglyme coating. Fibrinogen adsorption to the tetraglyme surface was measured with 125I-labeled fibrinogen and ToF-SIMS. Adsorption of fibrinogen to plasma deposited tetraglyme was less than 10 ng cm(-2), a 20-fold decrease compared to untreated FEP or tissue culture polystyrene (TCPS). Monocyte adhesion to plasma deposited tetraglyme was significantly lower than adhesion to FEP or TCPS. In addition, when the surfaces were preadsorbed with fibrinogen, fibronectin, or blood plasma, monocyte adhesion to plasma deposited tetraglyme after 2 h or 1 day was much lower than adhesion to FEP. RF-GDPD tetraglyme coating provides a promising approach to make non-fouling biomaterials that can inhibit non-specific material-host interactions and reduce the foreign body response. PMID- 11787524 TI - Engineered collagen-PEO nanofibers and fabrics. AB - Type I collagen-PEO fibers and non-woven fiber networks were produced by the electrospinning of a weak acid solution of purified collagen at ambient temperature and pressure. As determined by high-resolution SEM and TEM. fiber morphology was influenced by solution viscosity, conductivity, and flow rate. Uniform fibers with a diameter range of 100-150 nm were produced from a 2-wt% solution of collagen-PEO at a flow rate of 100 microl min(-1). Ultimate tensile strength and elastic modulus of the resulting non-woven fabrics was dependent upon the chosen weight ratio of the collagen-PEO blend. 1H NMR dipolar magnetization transfer analysis suggested that the superior mechanical properties, observed for collagen-PEO blends of weight ratio 1:1, were due to the maximization of intermolecular interactions between the PEO and collagen components. The process outlined herein provides a convenient, non-toxic, non denaturing approach for the generation collagen-containing nanofibers and non woven fabrics that have potential application in wound healing, tissue engineering, and as hemostatic agents. PMID- 11787525 TI - Protein adsorption on preadsorbed polyampholytic monolayers. AB - The adsorption behaviour of five different globular proteins on pure silicon substrates and on preadsorbed polyampholytic monolayers has been investigated as a function of protein concentration. The prelayers were prepared by adsorption of the ampholytic diblock copolymerpoly(methacrylic acid)-block poly((dimethylamino)ethyl methacrylate) (PMAA-b-PDMAEMA). This polyampholyte adsorbs in densely packed micelles directly from aqueous solution. Ellipsometry was used to determine the amount of adsorbed polyampholyte and protein. While ATR IR spectroscopy gives information about the adsorption and desorption behaviour of the preadsorbed polyampholytic layer, the lateral structures of the dried films were investigated by scanning force microscopy (SFM). The amount of protein adsorbed was found to be strongly influenced by the preadsorbed polyampholyte compared to the adsorption on the pure silicon substrates. No displacement of the polyampholyte by the proteins was detected. In most cases the protein adsorption was reduced by the preadsorbed polyampholytic layer. The observed trends are explained by the change in electrostatic and hydrophilic characteristics of the substrates. Furthermore, the entropy of adsorption has to be taken into account. PMID- 11787526 TI - Current status of cord blood banking and transplantation in the United States and Europe. AB - Cord blood (CB) transplantation has expanded the ability of the transplantation community to meet the growing needs of their patients. Clinical data over the last decade show promising results in CB transplantation using blood from related as well as unrelated donors. Basic science continues to look for ways to expand the quality and quantity of CB. CB banks are now established around the world, with major efforts to standardize banking to facilitate regulation, collection, processing, and distribution as a way of providing the highest-quality CB for patient use. This review article discusses the current status of CB transplantation and banking in the United States and Europe. PMID- 11787527 TI - Induction of stable long-term mixed hematopoietic chimerism following nonmyeloablative conditioning with T cell-depleting antibodies, cyclophosphamide, and thymic irradiation leads to donor-specific in vitro and in vivo tolerance. AB - BACKGROUND: Successful transplantation of solid organs relies on long-term immunosuppression for the prevention of graft rejection. Donor-specific tolerance without the need for continuous immunosuppression can be observed after allogeneic BMT. However, its routine use for tolerance induction has been precluded so far by the high conditioning-related toxicity of standard BMT regimens. Our laboratory has recently established a cyclophosphamide (CTX) plus thymic irradiation (TI)-based nonmyeloablative conditioning protocol for the treatment of hematologic malignancies. We have recently described the successful clinical application of this approach for the induction of donor-specific tolerance in a patient receiving a living-related kidney transplant, which resulted in graft acceptance without long-term immunosuppression. The aim of this study was to evaluate the induction and maintenance of host-versus-graft tolerance following this CTX-plus-TI-based regimen in a mouse model. METHODS: Induction of mixed hematopoietic chimerism and development of donor-specific tolerance following the CTX-based nonmyeloablative conditioning regimen (200 mg/kg CTX, in vivo T-cell depletion [anti-CD4 monoclonal antibody (MoAb) GK1.5 and anti-CD8 MoAb 2.43], and 7 Gy TI) was studied in the fully major histocompatibility complex (MHC)-mismatched B10.A (H2a)-->B6 (H2b) strain combination. RESULTS: The conditioning regimen allowed allogeneic bone marrow engraftment and persistent (>30 weeks) mixed lymphohematopoietic chimerism in almost all recipients. TI was essential to allow engraftment and development of tolerance, which was evident in all lasting chimeras. Compared to animals receiving a similar TBI-based conditioning regimen, overall levels of chimerism were significantly lower in the CTX-plus-TI-conditioned animals. However, donor specific tolerance in vitro and in vivo was evident in CTX-plus-TI-conditioned chimeras. Tolerance was associated with the presence of donor-type MHC class II+ cells in the thymus and deletion of donor-reactive cells, as determined by Mtv-8 and Mtv-9 superantigen-mediated deletion of Vbeta11+ and Vbeta5/1.2+ T cells. CONCLUSION: Engraftment, long-term chimerism, and induction of donor-specific tolerance can be achieved using a nonmyeloablative CTX-based conditioning regimen in fully MHC-mismatched BMT recipients without the induction of GVHD. PMID- 11787528 TI - Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches. AB - Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens. However, it is currently unclear how this radically different transplantation strategy affects immunological reconstitution. To address this important issue, we used T-cell receptor Vbeta spectratype analysis to examine the distribution of complementarity-determining region 3 (CDR3)-size bands as a measure of the complexity of the redeveloping T-cell repertoire. For this study, we evaluated the T-cell repertoire of 9 patients receiving T-cell replete, matched unrelated donor transplants following fully ablative or nonmyeloablative conditioning regimens. All 4 of the myeloablative and 2 of the nonmyeloablative patients received bone marrow, whereas 3 other nonmyeloablative patients received peripheral blood stem cells. The results of the spectratype analysis demonstrated that the patients who received nonmyeloablative conditioning together with either bone marrow or peripheral blood stem cells exhibited more rapid reconstitution of T-cell repertoire complexity. PMID- 11787529 TI - Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. AB - A multicenter investigation of allogeneic bone marrow transplantation for children with sickle cell disease was conducted that included 27 European and North American transplant centers. Fifty-nine patients who ranged in age from 3.3 to 15.9 years (median, 10.1 years) received HLA-identical sibling marrow allografts between September 1991 and April 2000. Fifty-five patients survive, and 50 survive free from sickle cell disease, with a median follow-up of 42.2 months (range, 11.8 to 115 months) after transplantation. Of the 50 patients with successful allografts, 13 developed stable mixed donor-host hematopoietic chimerism. The level of donor chimerism, measured > or =6 months after transplantation in peripheral blood, varied between 90% and 99% in 8 patients. Five additional patients had a lower proportion of donor cells (range, 11% to 74%). Among these 5 patients, hemoglobin levels varied between 11.2 and 14.2 g/dL (median, 11.3 g/dL; mean, 12.0 g/dL). In patients who had donors with a normal hemoglobin genotype (Hb), the Hb S fractions were 0%, 0%, and 7%, corresponding to donor chimerism levels of 67%, 74%, and 11%, respectively. Among patients who had donors with sickle trait, the Hb S fractions were 36% and 37%, corresponding to donor chimerism levels of 25% and 60%, respectively. Thus, allograft recipients with stable mixed chimerism had Rb S levels similar to donor levels, and only 1 patient required a red blood cell transfusion beyond 90 days posttransplantation. None of the patients have experienced painful events or other clinical complications related to sickle cell disease after transplantation. These observations strongly suggest that patients with sickle cell disease who develop persistent mixed hematopoietic chimerism after transplantation experience a significant ameliorative effect. PMID- 11787530 TI - Cytomegalovirus enteritis among hematopoietic stem cell transplant recipients. AB - Cytomegalovirus (CMV) is a cause of enteritis associated with hematopoietic stem cell transplantation (HSCT), but the natural history is rarely studied and hence poorly understood. CMV infection at this end-organ site is notably less frequent than is pneumonitis. To evaluate the spectrum of CMV enteritis after HSCT, we reviewed the database spanning 11.5 years of 2240 University of Minnesota transplantation patients for cases of gastrointestinal CMV. We identified 46 case patients. The incidence of CMV enteritis at 2 years following HSCT averaged 2% over the 11.5-year study interval. The median time to diagnosis of CMV enteritis after HSCT was 91 days (range, 17-527 days). The methods used in diagnosis included histopathology (58%) and virology (61%). Viremia was detected in two thirds of patients with CMV prior to the diagnosis of enteritis. Most treatment regimens included ganciclovir. The overall survival rate was 35% at 2 years following the onset of enteritis. PMID- 11787531 TI - Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with recurrent indolent non-Hodgkin's lymphoma. AB - PURPOSE: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL). PATIENTS AND METHODS: Twenty-six patients with recurrent indolent NHL or MCL were mobilized witheither granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: > or =5 x 10(5) viable and pure HSC/kg; cohort 2: > or =3 x 10(5) HSC/kg). RESULTS: We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/microL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/microL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point posttransplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%. CONCLUSIONS: CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population. PMID- 11787532 TI - From breast cancer to Comprehensive Women's Center. AB - A Comprehensive Women's Center (CWC) is a concept designed to enhance the quality of both patient care and the care experience while increasing patient volumes to hospitals by detection of conditions requiring additional diagnostic interventions or therapeutic interventions. Expanding an existing Breast Center into a Comprehensive Women's Center attracts new patients by diversifying services offered from mammography and breast related services alone to providing services such as bone densitometry, cholesterol screening and even children's immunizations. A Comprehensive Women's Center also positions the hospital as the site of choice for women making healthcare decisions. The CWC will enhance the quality of women's health by increasing compliance with screening guidelines through ease of access and quality of services provided. PMID- 11787533 TI - DHHS issues guidance to address privacy rule uncertainties. PMID- 11787534 TI - Sexually dimorphic ontogenetic trajectories of frontal sinus cross sections. AB - In this paper, we analyze a large published data set of cross sections of frontal sinuses of 3 to 11-year-olds (105 males and 87 females) from Central Europe to investigate several issues relating to frontal sinus ontogeny. Despite a large variation in every one year age cohort, we detect no asymmetry of the left average versus the right average frontal sinus lobe cross-sectional areas in the population, neither for males nor for females. The growth rate is shown to be nonuniform and differs between males and females. We demonstrate the use of a sigmoid function interpolation to characterize one aspect of ontogeny, namely, the functional relation between the cross-sectional area of the frontal sinus and the age of the individual. Ontogenetic trajectories of these cross-sectional areas are remarkably well modeled by a sigmoid function (logistic curve) with suitably estimated parameters for development up to an age of 11 years (females) and 9 years (males). However, these developmental curves also reliably predict the average adult cross-sectional area at age 19 (99% for females, 95% for males). Apart from possible inadequacies of the data set, we also discuss the possibility of heterochrony in the ontogenetic trajectory before versus after puberty. PMID- 11787536 TI - Genealogical structuring of a population. AB - The study observed population of 484 generation restrictive genealogies collected in four Croatian regions during 1970/71 within "The study of fat and carbohydrate metabolism indicators correlated with the occurrence of diabetes in animal fat and oil consuming population groups". The genealogies were collected on two islands (Brac and Hvar) and in two continental regions (Sinjska Krajina and Srijem). Genealogy Structure Index (GSI) was defined as quantitative indicator of genealogy structure. GSI was continuos variable which, by its extreme, describes vertical and horizontal type of genealogy structure, independently of the way genealogies were collected. Genealogy structure of surveyed population was described on the basis of participation of different genealogy types. Populations of the island Hvar and Brac showed to have horizontal genealogy type, continental population of Sinjska Krajina showed to have mixed type and continental population of Srijem showed to have vertical type of genealogy structure. PMID- 11787535 TI - Biological, epidemiological and clinical basis of understanding human immunodeficiency virus infection. AB - Human immunodeficiency virus (HIV) causes a chronic infection beginning in most individuals with an acute syndrome followed by an asymptomatic stage and progresses in untreated adults over a median of 10 years to the late stage called AIDS. The virus rapidly and enormously replicates from the initiation of infection. The principal immunodeficiency caused by HIV is depletion in the subset of T lymphocytes referred to as helper T cells. New anti-HIV drugs given in potent combination regimens have demonstrated impressive efficacy by both clinical and laboratory measures, and have provided evidence that drugs can suppress HIV replication and disease manifestations. HIV/AIDS is still uncommon in Croatia. In the period from 1986 to 2000, 171 patients with AIDS have been reported of whom 101 (59%) died. The incidence of AIDS in 2000 was about 4 cases per million inhabitants. Recent testing of injection drug users at a needle exchange program (Help, Split) revealed an HIV incidence of about 1%. PMID- 11787537 TI - Estimation of sex from the talus in prehistoric Native Americans. AB - We present both a multivariate discriminant analysis and a univariate procedure to estimate sex from measures of the talus (length, width and height). Both methods are comparable in accuracy (about 85%), but the univariate procedure ispreferred due to its simplicity. PMID- 11787538 TI - Expert model of decision-making system for efficient orientation of basketball players to positions and roles in the game--empirical verification. AB - The purpose of the research was to empirically verify the expert model system designed for more efficient orientation of basketball players to particular positions and /or roles in the game (specialization). Participants were 60 randomly chosen male basketball players (12 players per each position) from the 12 Croatian 1st league teams in season 1998/99. Data were gathered from 10 basketball coaches who estimated overall performance (actual quality) of players on defense (7 variables) and on offense (12 variables). Variables were established by Trninic, Perica and Dizdar. A measure of body height was added to the aforementioned group of variables. The results obtained suggest that the proposed decision-making system can be used as an auxiliary instrument in orienting players to the positions and roles in the game. It has been established that the players have attained the highest grades of overall performance exactly at their primary playing positions in the game. The largest differences were determined between point guards (position 1) and centers (position 5). The greatest difficulties have occurred in determining optimal position for small forwards (position 3), then for shooting guards (position 2) and, last, for power forwards (position 4), because all these basketball players are the most versatile ones. Therefore, reliability of the system is the lowest when it is applied for selecting and orientating players to these positions. Convenient body height significantly contributes to aptitude of these players to play multiple positions and to assume multiple roles in the game. This research has reinforced the thesis that body height is a variable with the greatest influence on orientation of players to particular positions and roles in the game. PMID- 11787539 TI - Effect of specially programmed physical and health education on motor fitness of seven-year-old school children. AB - The efficacy of specially programmed physical and health education on the motor development of first-grade pupils was analyzed in a sample of 633 children aged 7 years. Pupils have been divided into control group consisting of 140 boys and 137 girls attending standard program of physical and health education, and in experimental group consisting of 184 boys and 172 girls attending specially programmed physical and health education. A battery of 12 motor tests has been used on two occasions separated by nine-month interval. Analysis of time-changes (by using the model of differences) pointed to the significantly greater quantitative changes in experimental group compared with control group of children. In boys, the changes are obtained for the tests of aerobic endurance, static strength, flexibility, speed, explosive strength of sprint and throw type, and equilibrium, and in girls, they are for aerobic endurance, static strength, explosive strength of throw and sprint type, flexibility, repetitive strength, speed, and equilibrium. PMID- 11787540 TI - Sexual dimorphism: asymmetry and diversity of 38 dermatoglyphic traits in five endogamous populations of West Bengal, India. AB - Five hundred families from five different endogamous populations encompass the main social rank in the caste hierarchy of West Bengal, India were analyzed for the present report. With the aim of comparing dermatoglyphic sexual dimorphism among the groups, analysis of variance and principal component analysis were performed, based on 38 dermatoglyphic variables. Sex dimorphism is homogeneous in nature in all populations, indicating common characteristics of dermatoglyphic variables within the same geographic area. But sex differences display different levels when compared with other racial groups. Therefore, sex differences are different in diverse populations. This would explain the existence of the possible role of environmental prenatal factors in the realization of the level of dermatoglyphic sex differences. Sex differences in asymmetry indices are less pronounced, which indicates that Indian populations are less asymmetric compared to Jewish populations. Fluctuating asymmetry, which is greater in females compared to males, support the hypothesis of Livshits and Kobyliansky--"increased heterozygosity is often associated with a decreased phenotypic variability including a diminished fluctuating asymmetry". A common feature of the principal component factor 1 "digital pattern size factor", in diverse populations indicates its degree of universality, and suggests that the variability of finger ridge counts is determined by the same genes which control the pattern types. The factors "finger ridge count diversity factor", "directional asymmetry factor", "fluctuating asymmetry factor", and "bilateral asymmetry factor" was perhaps described in the literature for the first time in Indian populations. The nature of variation of these components among these populations and between sexes, appears with a good similarity which suggests their biological validity of the underlying component structure. The overall homogeneity of sex dimorphism among 5 populations is well pronounced. PMID- 11787541 TI - Culture and biology: surnames in evaluating genetic relationships among the ethnic minorities of Southern Italy and Sicily. AB - Surnames of grandparents were collected from children in the primary schools of the Albanian-Italian, Croat-Italian, and Greek-Italian villages. The coefficients of relationships by isonymy show almost no relationship with ethnicity. Ethnolinguistic minorities of Southern Italy and Sicily are geographically subdivided in two main clusters: the first cluster comprises the Albanian, Croat, and Greek communities of the Adriatic area; and the second cluster comprises the Albanian communities of the Ionian, Thirrenian and Sicilian area. The Greeks of Reggio Calabria Province are completely separated from the other communities. PMID- 11787542 TI - Urban adolescents and sexual risk taking. AB - The paper analyzes socio-cultural and psychosocial factors affecting sexual activities and related risk-taking behaviors in Croatian high-school students. It attempts to determine the correlates of sexual activity, early sexual initiation, the number of sexual partners, and the use of contraceptives and condoms. Due to the gender-specific trajectories of sexual socialization and initiation, all the analyses were carried out separately for female and male students. The results point out gender-specific structure of adolescent sexual risk-taking, clustering of risk-taking activities, and the habitual character of sexual risk-taking. These findings should be instrumental for the development of a comprehensive school-based sex education curriculum that Croatia lacks. PMID- 11787543 TI - Sexual dimorphism in body composition, weight status and growth in prepubertal school chiildren from rural areas of eastern Austria. AB - Sexual dimorphism in stature, weight status and body composition were analyzed in a sample of 398 prepubertal children (213 girls, 185 boys) ageing between 7 and 10. Furthermore the prevalence of overweight was tested. Body composition parameters were determined using TBF 105 Body composition analyzer according to BIA-method. Highly significant sex differences in body composition were observed (p < 0.001). In contrast, stature, weight and BMI showed no significant differences between the two sexes. Nevertheless, a significant higher portion (p < 0.05) of girls (29%) corresponded to the definition overweight according to ASNS (Austrian Survey of Nutritional Status), while only 20% of the boys felt into the category overweight. The results of the present study showed not only significant sex differences in body composition, especially in fat mass, long before puberty onset, but also a significantly higher prevalence of overweight among prepubertal girls in comparison to prepubertal boys. PMID- 11787544 TI - Psychodynamics and regression of social groups. AB - The paper discusses same aspects of psychodynamics and regression of social groups. The aims of the study are: 1. to promote the understanding of group processes which point out the presence of complex phenomena within social group and should help group members and a group leader to function on the higher level of sensitivity, capability and effectiveness; 2. to stimulate the knowledge implementation in problem resolving among social groups (organizations). The group psychodynamic, group regression and mechanisms against it, are theoretically based on aspects of psychoanalytic group psychology, using the method of descriptive literature overlook. CONCLUSION: the permanent evaluation of group functioning, group situation and group processes by some group members and by the whole group are conditions for preservation of regressive group phenomena on rather low level, or successful functioning on more mature level, creating the feeling of satisfaction in group and among its members. PMID- 11787545 TI - The assessment of the analytic group treatment efficiency according to Yalom's classification. AB - The authors expose the assessment of therapeutic factors during group analytic treatment. In the methodology of research several measuring instruments were applied. In this study it will be exposed the results obtain by Yalom's questionnaire containing 60 items. Three small analytic groups were followed up, encompassing 20 group members. By self-evaluation they ranked the assessment of every of 12 therapeutic factors according to their importance. The variability of results was shown more inside then among groups. The highest-ranking therapeutic factors the group members sorted out were: self-understanding, family re enactment, cohesiveness and universality. The factor of identification was the lowest ranking in all groups. PMID- 11787546 TI - Aggression and alcoholism. AB - Alcoholism is today the greatest medical and social problem. Due to the fact that it is frequently connected with aggressiveness, it can also be defined as a great and frequent forensic problem. The authors investigate the issue to what extent aggressiveness is medically justified. They offer guidelines regarding this problem in accordance with their everyday experience and medical criteria. PMID- 11787547 TI - Weather types and traffic accidents. AB - Traffic accident data for the Zagreb area for the 1981-1982 period were analyzed to investigate possible relationships between the daily number of accidents and the weather conditions that occurred for the 5 consecutive days, starting two days before the particular day. In the statistical analysis of low accident days weather type classification developed by Poje was used. For the high accident days a detailed analyses of surface and radiosonde data were performed in order to identify possible front passages. A test for independence by contingency table confirmed that conditional probability of the day with small number of accidents is the highest, provided that one day after it "N" or "NW" weather types occur, while it is the smallest for "N1" and "Bc" types. For the remaining 4 days of the examined periods dependence was not statistically confirmed. However, northern ("N", "NE" and "NW") and anticyclonic ("Vc", "V4", "V3", "V2" and "mv") weather types predominated during 5-days intervals related to the days with small number of accidents. On the contrary, the weather types with cyclonic characteristics ("N1", "N2", "N3", "Bc", "Dol1" and "Dol"), that are generally accompanied by fronts, were the rarest. For 85% days with large number of accidents, which had not been caused by objective circumstances (such as poor visibility, damaged or slippery road etc.), at least one front passage was recorded during the 3-days period, starting one day before the day with large number of accidents. PMID- 11787548 TI - Treatment of supracondylar humerus fractures in children: minimal possible duration of immobilization. AB - In the period from January 1980 until December 1990 we treated 147 children and adolescents with supracondylar humerus fracture, and followed the outcome in 127 of them. Three (2.4%) patients had no displacement of fractured bones and were treated only with plaster cast immobilization. Twenty three (18.1%) underwent closed reduction of fragments and application of a plaster cast. The majority (97; 76.4%) required manual reduction and the fixation of segments with Kirschner's wires laterally and medially. Four (3.1%) patients were treated with open reduction and fixation with Kirschner's wires. Both plaster cast immobilization and fragment fixation with Kirschner's wires lasted only 14 days and were immediately followed by rehabilitation. Such a short immobilization of extremities or fixation offragments did not result in any complication. Of 56 children available for long-term follow-up, we achieved excellent treatment results in 43 (76.6%) of the patients, good and fair in 12 (21.5%), and a poor result in only 1 patient (1.8%). There were no permanent vascular or neurological complications apart from slight weakness of the ulnar nerve in 3 patients. In conclusion 14 days seemed to be the biological minimum of time needed for this type offracture to heal in children and adolescents. Fixation of the fragments with Kirschner's wires and immobilization of the extremity for only 14 days brings a significant reduction of total treatment expenses, avoids repeated x-ray examination, facilitates early physical therapy and returns the child to its family. PMID- 11787549 TI - Investigation of hip joint prosthesis damage. AB - Following total hip arthroplasty the durability of a prosthetic implant depends on many factors but is generally limited by two types of damage: wearing of frictional surfaces of the acetabular and femoral component as well as the loosening and migration of the "rosthesis-cement-bone" system. Since it is possible to establish a cause-and-effect relationship between these two damage types, the aim of this research is to investigate the phenomena related to the contact surface and their influence on the prosthesis-bone relationship in general for various sizes and conditions of loading of the hip joint. The experimental study was conducted using a Timken testing device modified in such a way that simulation of relative movements of the joint elements was achieved using a mechanism that produces conditions similar to those in the human hip joint. The analysis of obtained measurements showed that actual radii of friction of the hip prosthesis did not correspond to the theoretical ones and that only a small portion of the total friction surface is realized. Variations of the radius of friction for the examined prosthesis type were very large, which changes the hypotheses on the ability of the prosthetic head and the "prosthesis-cement-bone" system to bear a certain amount of load. The construction and design of prosthetic implant components has a significant influence on both the amount of wear at the site of contact and the loosening of prosthesis. PMID- 11787550 TI - The compact formulation of anthropodynamical measures in physiological anthropology. AB - In this paper, an interdisciplinary combination of several state-of-art methods from biomechanics, modeling and multibody dynamics of the humans is described. The description of the human figure in the motion is a very important part of biomechanical analysis. In such current methods it is necessary to us mass moment of inertia as a part of the fundamental dynamic anthropomeasure when describing this motion. The goal of this work is to use and modify existing techniques and to investigate what have to be analyzed to make them work together. First, some general definitions and descriptions of mass moment of inertia adapted to anthropometric values of our population. Second, there is also a review of some simple models by means of which it is possible to calculate distribution of the body-part masses during the motion. The results are given in the form of equations and tables which present the functions between selected body parts anthropodynamical measures and percentile distribution values of males as well as females of Croatian population. PMID- 11787551 TI - The relationship between left ventricular filling shortly after an uncomplicated myocardial infarction and subsequent exercise capacity. AB - Resting measurement of only left ventricular systolic function, is not enough sufficient parameter that predicts exercise capacity in patients with cardiac disease. Therefore, left ventricular filling shortly after an acute myocardial infarction (AMI) was prospectively studied to determine whether it could predict subsequent exercise time. Consecutive AMI patients underwent Doppler and two dimensional echocardiography within 48 hours of infarction. The study group consisted of 63 participants: 33 patients with an uncomplicated AMI who had undergone symptom-limited stress testing during recovery and 30 healthy subjects. Systolic function was evaluated by wall motion score index (WMSI), and diastolic one was assessed by the peak transmitral Doppler velocity in early diastole (E) and atrial systole (A), then by their ratio (E/A), normalized E/A ratio, and by diastolic filling period (DFP). Myocardial infarction (MI) size was measured electrocardiographically, using Selvester's QRS scoring system (QRSSI) and then expressed in percentages. Healthy participants and patients were compared, through common parameters. The patients receiving BB treatment at the time of exercise testing, had a lower resting pulse, and achieved a lower maximal pulse, yet their exercise time was similar incomparison to that of the group not receiving BB therapy. Our results have shown a strong positive correlation between exercise time and WMSI (r = 0.77, p < 0.001) DFP (r = 0.56, p < 0.001), respectively weak negative correlation with QRSSI (r = -0.17, p < 0.001) and better negative correlation with normalized E/A ratio (r = -0.56, p < 0.001). This correlation was not influenced by beta-blokers (BB) at the time of stress testing. Normalized E/A ratio and DFP are the only diastolic function parameters, which predict exercise capacity during recovery, measured soon after an uncomplicated AMI. PMID- 11787552 TI - Transcranial Doppler in smoking relapse prevention strategy. AB - Nicotine dependence is a progressive, chronic, relapsing disorder. Nicotine is the principal and most potent psychopharmacologically active component of tobacco smoke. Through activation of nicotine receptors in the central nervous system, nicotine can lead to tolerance and dependence. Cessation of smoking is followed by severe pathophysiologic withdrawal and by long-term craving. TCD measurement of cerebral blood flow velocity (BFV) and nicotine dependence degree measured by Fragestrom questionnaire was analyzed in relation to smoking relapse. This study includes 47 participants (25 females and 22 males) included in Breathe Free Plan To Stop Smoking in Non Smoking School in Zagreb. 12 month following the end of treatment participants were divided in three groups: continued abstinence, interrupted abstinence and non abstinence. High nicotine dependence combined with TCD pathological finding significantly discriminated successes and failures, suggesting that smokers with pathological TCD need specific therapeutic approach with more social support, individualized coping skills and cognitive restructuring. Measuring cerebral flow velocity by transcranial Doppler in smokers showed the practical validity in prediction of smoking relapse. PMID- 11787553 TI - Factors predisposing to early childhood caries (ECC) in children of pre-school age in the city of Zagreb, Croatia. AB - The aim of this study was to investigate factors predisposing to early childhood caries (ECC) in pre-school children in the city of Zagreb, Croatia. The investigation was carried out on the sample of 145 children (77 boys and 68 girls) aged between 2 and 5 years, including clinical examination of dental status and survey on the habits among the parents. The overall prevalence of ECC was 30%: in girls it was 25%, and in boys 48%. The study on the risk factors was designed as a classic case-control study. The mean value of dmfs index among the cases amounted to 8.6, in comparison to 5.2 in the control group (p<0.05). Bottle feeding did not represent a significant risk, but night consumption of sweet beverages after first 24 months and the lack of introduction of teeth-brushing habit after first 24 months did (p < 0.001 for both predictors). The study revealed the importance of early introduction of teeth-brushing and giving up the nightly consumption of sweet beverages in prevention of ECC. PMID- 11787554 TI - Hypohidrotic ectodermal dysplasia: dental features and carriers detection. AB - Ectodermal dysplasia is a heterogeneous condition characterized by affected ectodermal structures, among which the teeth and skin with its derivatives (hair sweat glands) are the most frequent. The aim of this work is to present the analysis of dental traits in five families (affected boys and their mothers) with hypohidrotic ectodermal dysplasia (HED), and to evaluate the importance of orofacial and dental findings in the determination of female HED gene carriers. Hypodontia (oligodontia) was found in all the patients. The mothers, gene carriers, had either hypodontia or a reduced size of teeth with a particular morphological, peg shape. In patients with hypohidrotic ectodermal dysplasia the deciduous second molar teeth were mostly affected by taurodontism. The characteristic dental finding in heterozygous females of the mandibular peg shaped incisors and canines, as well as of hypodontia or peg shaped upper lateral incisors can be used as a reliable criterion for the detection of HED gene carriers. PMID- 11787555 TI - Some anthropometric characteristics, reactions on physical stress, and blood pressure in males aged 18 in "Primorsko-Goranska" County, Croatia. AB - The paper presents the distribution and average values of some anthropometric characteristics in 1,210 males aged 18 in "Primorsko-Goranska" County, as well as some manifestations of physical fitness parameters and some correlations between these two groups of characteristics. The prevalence of hypertensive and limit values for systolic blood pressure (SBP) was 8.6% and for diastolic blood pressure (DBP) 2.1%. Body weight and body mass index were in a significantly positive correlation with SBP and DBP Body mass index showed a significantly positive correlation with heart rate after step-test. Therefore, it can be concluded that overweight reduces tolerance on workload. PMID- 11787556 TI - Analysis of occlusal contacts in different types of prosthodontic appliances, Eichner classifications, presence RCP-ICP slide and the type of occlusion. AB - The aim of the study was to determine the number and the type of the occlusal contacts (strong, weak) with respect to the type of the prosthodontic appliance (fixed, removable, combined fixed-removable) and with respect to the Eichner classification in patients with their appliances being in a good function for a long time. The aim of the study was also to determine the number and the type of the occlusal contacts (strong, weak) with respect to the type of occlusion (canine guided, group function or balanced) and the presence of the RCP-ICP slide. A total of 440 patients with different types of prosthodontic appliances were examined for the antagonistic occlusal contacts using occlusal strips of 11 microm and 50 microm. The average number of occlusal contacts was 10.5 for the upper and 10.46 for the lower posterior teeth, approximately 5 on each side of the tooth arch. The results of the study suggest that the biggest number of occlusal contacts were recorded for the small span fixed appliances (2 on average), the greater span fixed and fixed-removable prosthodontic appliances exhibited 1.6 occlusal contacts, and the removable complete denture exhibited 1.2 contact per the tooth in the posterior region. The number of the hard occlusal contacts was significantly greater in fixed and fixed-removable prosthodontic appliances in comparison with the complete dentures (p < 0.05), while there was no significant difference between the prosthodontic appliances for the weak occlusal contacts (p > 0.05). The overall number of the occlusal contacts, as well as the number of the hard occlusal contacts was significantly greater in the Eichner class I cases (p < 0.05) in comparison with the Eichner classes II and III. The number of the weak occlusal contacts showed no significant differences with respect to the Eichner classification (p > 0.05). There was no significant difference in the number of occlusal contacts between the appliances with RCP-ICP slide and where ICP and RCP corresponded (p > 0.05). PMID- 11787557 TI - Evaluation of denture stomatitis in Croatian adult population. AB - Denture stomatitis (DS) is often found under the removable partial dentures (RPDs). There are many factors influencing it, such as patient's age and gender, smoking habits, denture age, denture material, denture wearing habits, denture hygiene habits, oral hygiene instruction, denture cleanness and denture plaque accumulation. The aim of this study was to find out the influence these factors have on the prevalence of DS under RPDs and complete dentures (CDs). A total of 200 patients took part in this study. Half of the examined patients (100) wore CD and the other half (100) RPDs. There were 63 males and 137 females, aged between 45 and 83 years. Different smoking habits, denture wearing habits, denture hygiene habits, denture cleanness and oral hygiene instructions had significant influence on the degree of DS in CD wearers (p < 0.01). In the RPD wearers, denture material and denture support had a significant influence on DS (p < 0.01). The significant correlation was found between the denture plaque accumulation and the DS in complete maxillary and mandibular (rhoU = 0.85; rhoL = 0.61) and removable maxillary and mandibular partial dentures (rhoU = 0.45; rhoL = 0.62). PMID- 11787558 TI - Foramen mandibulae as an indicator of successful conduction anesthesia. AB - Comparative measurements were made of 144 orthopantomographs in 50 patients with successful and 94 patients with unsuccessful inferior alveolar nerve block anesthesia. The results show that the bony lingula is prominent in 28.5% of all patients, or in 56.0% of those with unsuccessful anesthesia. The variables mandibular notch vs. mandibular foramen (MN-MF) and the anterior ramus ridge vs. mandibular foramen (ARR-MF) show greater distances in the group of patients with successful anesthesia, while the variables of posterior ramus ridge vs. mandibular foramen (PRR-MF) and mandibular angle vs. mandibular foramen (MA-MF) were greater in the group of patients with unsuccessful anesthesia (p > 0.05). It is concluded that the variability in position of the mandibular foramen among others may be responsible for an occasional failure of inferior alveolar nerve block. PMID- 11787559 TI - The development of blood and lymph vessels of human parathyroid glands in embryonal, fetal and postnatal period. AB - The aim of the article is to investigate the development of blood and lymph systems in human parathyroid glands in prenatal and postnatal periods. The first capillaries are observed in these glands already in the lunar month 2. At the middle of pregnancy blood supply is increased, being extremely abundant in lunar months 9 and 10, as well as during the first year of life. As parts of the lymph system, intercellular lymph spaces are noticed in the parathyroid glands already in the lunar month 2, and also later, when lymph vessels are situated along the gland or in its connective capsule and within the gland parenchyma respectively. All these findings could be connected with the early function of these glands, as well as with the possibility that parathyroid hormone (PTH) is not transferred by blood only but by lymph as well. PMID- 11787560 TI - Hepatocyte growth factor levels in Croatian healthy and alcoholic liver cirrhosis patients. AB - Hepatocyte growth factor (HGF) is a most potent hepatocyte mitogen, and plays a mayor role in liver regeneration during injury. The aim of this study was to evaluate HGF values in Croatian healthy and alcoholic liver cirrhosis patients (AC). The HGF and standard laboratory tests of liver damage were measured in 33 AC patients, and 41 healthy subjects. HGF was measured by using an ELISA method. The HGF levels were higher in cirrhotic patients than in healthy subjects (median value is 0.78 vs. 0.19 ng/ml, p < 0.001). Japanese study showed similar values of HGF for healthy subjects and AC subjects. The HGF values in patients depend on grade of illness. There was found significant correlation between HGF and almost all standard liver damage tests. The ROC analysis showed that measuring of HGF had convincingly best accuracy than other parameters, and seems to be useful in classifying grade of illness. PMID- 11787561 TI - Lung lavage neutrophils, neutrophil elastase and albumin in the prognosis of pulmonary sarcoidosis. AB - The authors measured the bronchoalveolar lavage fluid (BALF) neutrophils, neutrophil elastase and albumin in 60 patients with pulmonary sarcoidosis, 18 patients with other interstitial lung diseases and 14 healthy controls in order to evaluate its significance in the prognosis of sarcoidosis. The concentrations were measured by enzymoimmunoassay and radial immunodiffusion (LC plates). Obtained values were correlated with some clinical indices, radiological stage and lung function values. The patients were followed up for 22.3 +/- 6.8 months. At the end of observation period the outcome of sarcoidosis has been evaluated upon the findings of chest radiograms and lung function tests. The length of duration of the disease correlated with the lung lavage neutrophil counts (r = 0.2535; p < 0.05). Significantly higher values of BALF elastase were obtained in III radiologic stage than II and I. Patients with high BALF albumin had more often dispnoa (p < 0.05) and chronic forms of the disease (p < 0. 05). The values were high in patients in II and III radiologic stage. Unfavorable outcome of chest radiograms was announced by high BALF albumins (p < 0.05). The measurement of BALF neutrophils, neutrophil elastase and albumin are helpful in clinical management and estimation of the prognosis in patients with pulmonary sarcoidosis. PMID- 11787562 TI - Event-related potentials in medical workers with long-term exposure to xylene. AB - The effects of chronic exposure to xylene on cognitive ability were studied in a group of 35 medical workers occupationally exposed to low-level concentrations of xylene for at least five years by using event-related potentials (ERPs), and compared with a control group of 21 subjects. The exposure to xylene was confirmed through determination of m-methylhippuric acid, a reliable biological indicator of xylene exposure, in pre- and post-shift urine. A dose-effect relationship between log m-methylhippuric acid and ERP log latency (p = 0.032), and the ERP amplitude (p = 0.047) was statistically significant. The group of medical workers showed significantly longer ERP log latency (p < 0.001) than did the control group with respect to factors of exposure to smoking, education and age as covariates. For the ERP amplitude the difference was found not to be significant (p = 0.263), probably due to high between subject variability. The cognitive impairment may occur in workers chronically exposed to xylene. PMID- 11787563 TI - Mediterranean islands: a concept. AB - This article represents some of the results of my fieldwork and research on the islands of Sardinia, Corsica, Malta, Sicily, Crete and Susak between the years 1962-1986. My main field-work in Sardinia was supported by the Social Science Research Council, London and the University of Reading/Berks, and the ones in Corsica, Malta and Sardinia by the Department of Ethnology, University of Cologne (Institut fur Volkerkunde, Universitat Koln) forming a part of a project on the Mediterranean of which I was in charge. The above research was also related to my M.A. Course on "Mediterranean Peasant Societies and Social Structures" taught at the Graduate School of European and International Studies, University of Reading between 1978-1994. The main purpose of the article is to demonstrate the role of the islands in the Mediterranean, especially their ability in preserving their identity in spite of many incursions from outside. Islands became symbolized by their systems of values, and the ability to survive any attempt of conquest or change. In this the islands received a great help in the environment which helped these islands to remain unique and isolated until the present day. PMID- 11787564 TI - Gastrointestinal pseudo-obstruction: report of a patient with postoperative pseudo-obstruction. AB - Postoperative pseudo-obstruction is a rare state of protracted gastrointestinal paresis that may progress to paralysis without the presence of obstructive lesions. Pseudo-obstruction is usually, but not exclusively, associated with an abdominal operative procedure (laparotomy), however, it may occasionally occur following extra-abdominal operations. As differentiated from the usual, 'physiologic'postoperative paresis, pseudo-obstruction persists for more than 7 days. The pathogenesis of postoperative pseudo-obstruction is complex and as yet partially unknown. Whereas the 'physiologic' postoperative gastrointestinal paresis includes short-term functional cholinergic depression of the visceral organs, in pseudo-obstruction focal lesions in the region of Auerbach's plexus, manifesting as visceral neuromyopathy, are involved. That is why the 'physiologic' postoperative paresis never transforms into paralytic ileus, while in pseudo-obstruction such a risk is potentially involved. The treatment for pseudo-obstruction is as a rule conservative. Surgical treatment (cecostomy) is rarely required. Colonoscopic decompresive suction is usually enough to eliminate the risk of colon rupture due to extensive distention by fast growing meteorism. A patient with postoperative pseudo-obstruction is presented. PMID- 11787565 TI - Growth and development of male children and youth in Tuzla's region after the war in Bosnia and Herzegovina. AB - A four-year aggression on Bosnia and Herzegovina was extremely unfavourable period for growth and development of children and youth. In spite of that, it is established that ontogeny of male children and youth (between 10.5-19.5 years) on the observed region is going well, and it is within the limits at the average European standards. By parallel analysis of growth of domestic and expatriate persons, it is established that the average (sum) values of almost it's all indexes are significantly bigger for domestic (object) inhabitants. However, after the end of growth, they become approximately the same. By comparison of indexes of growth and development of the tested sample and samples from 1980 (of the same population), the soft acceleration trend for majority (indexes) of parameters is established, what is mostly seen in postpuberty age. The tested persons in pre-puberty and puberty age had the same or even less average values comparing to the tested persons from 1980. This is probably a direct result of negative influence of exogenous factors (war vital conditions), which caused temporary stoppage in growth and development in that period of growth when growth is the most intensive. Despite the fact that war life conditions have negatively affected the growth and development of the subjects studied, it has been found that the development of male children and youth, meaning the growth of different parameters on the studied area were in synchrony. PMID- 11787566 TI - Influence of father's weight and height on weight of male and female newborns. AB - The study included 1,596 newborns and their parents living in Sibenik County, Croatia. All newborns are born between 37 and 42 weeks of gestation, with no congenital anomalies and from a single pregnancy. Fathers and mothers of male babies are older than those of girl babies (p < 0.01). Mean values for weight, height, BMI in parents and the woman's parity are equal (p = 0.05). Pregnancy with male baby lasts longer and the babies are heavier (p < 0.05). Where the fathers weight between 70 and 79 kg and 80 to 89 kg, and where the fathers are 175 to 179 cm or 180 to 184 cm tall with normal BMI the male babies are heavier than the females at birth (p < 0.05). Increased weight, height and BMI in the father increase the birth weight of both male and female babies (p < 0.00001). The authors concludes that the parents (father and/or mother) of male babies are older than those of girls, that pregnancy for males babies lasts longer and that male babies are born heavier than girls. With increased weight, and height and BMI in the father, the birth weight of both male and female babies increases. PMID- 11787567 TI - Geographical distribution of elderly people in Croatia. AB - The authors outlined the geographical distribution of individuals displaying longevity in the Republic of Croatia. Elderly people, aged 80 years and older, have been the subject of this study and were viewed in several aspects including the number of elderly people and age-specific mortality rate by districts. Data for the years 1981 and 1991 were reviewed. In 1981 there were 73,052 (1.6%) persons aged 80 or older. Ten years later in 1991 their number had increased to 107,256, which was 2.2% of the whole population. Most of the elderly people live on the islands, in the district of Dubrovnik and in Lika, which is in the continental part of Croatia. There are more women than men among those aged 80 years and older Age-specific mortality rate in 1981 in Croatia was 170 and in 1991 151 per 1,000 elderly people. In women the rate was 162 in 1981 and 141 in 1991, per 1,000 elderly people. The death rate was higher in men; in 1981 it was 201 and in 1991, 172 per 1,000 elderly people. We can see that the specific mortality rate had fallen in 1991 compared to 1981. The age specific mortality rate varies from district to district. In 1991 the lowest, 110 per 1,000, was in Lika, and the highest in the districts of Varazdin (182 per 1,000), Bjelovar (178 per 1,000) and Zagorje (175 per 1,000). The death rate was higher amongst elderly men (172.31 per 1,000) than elderly women (141.65 per 1,000). The smallest number of those aged 80 years and older with a high death rate is found in Slavonia. The opposite--a high number of elderly people and a low specific mortality rate--can be seen in the district of Lika. On the islands the number of elderly people is high, especially women, and surprisingly, the specific mortality rate is relatively high as well. PMID- 11787569 TI - Blood pressure and its biocultural correlates among the Lepchas of Sikkim, India: a microlevel epidemiological study. AB - The present study evaluates the blood pressure profile among the Buddhist Lepchas, a tribal population, indigenous to the Sikkim Himalaya, in relation to selected biological, behavioral and sociocultural factors. The study subjects (aged 16 years and older) have been chosen from urban (Gangtok town, the capital of the State of Sikkim) and rural (Dzongu villages, about 75 km north of Gangtok) areas. The subjects inhabiting the urban area are engaged primarily in service sector, while those inhabiting the rural area are practicing agri-horticulture. The results reveal that significant age effect exists on logarithmically transformed blood pressures; sex effect is not significant. Among the anthropometric variables considered, calfgirth and height are found to be significantly correlated with systolic and diastolic blood pressures, respectively. While disease status significantly affects systolic pressure, a significant effect of alcohol intake is discernible only on diastolic pressure. Furthermore, significant effects of rural/urban residence and educational level are found on blood pressures, both systolic and diastolic. Mean systolic and diastolic blood pressures of the urban Lepchas are found to be significantly higher compared to their rural counterparts. An increase in both mean systolic and diastolic pressures is noticed with increasing level of education, although the trend is not absolutely uniform. PMID- 11787568 TI - A large cross-sectional study of health attitudes, knowledge, behaviour and risks in the post-war Croatian population (the First Croatian Health Project). AB - As the liberation of occupied Croatian territories ended the war in the country in 1995, the Ministry of Health and Croatian Health Insurance Institute have agreed to create the new framework for developing a long-term strategy of public health planning, prevention and intervention. They provided financial resources to develop the First Croatian Health Project, the rest of the support coming from the World Bank loan and the National Institute of Public Health. A large cross sectional study was designed aiming to assess health attitudes, knowledge, behaviour and risks in the post-war Croatian population. The large field study was carried out by the Institute for Anthropological Research with technical support from the National Institute of Public Health. The field study was completed between 1995-1997. It included about 10,000 adult volunteers from all 21 Croatian counties. The geographic distribution of the sample covered both coastal and continental areas of Croatia and included rural and urban environments. The specific measurements included antropometry (body mass index and blood pressure). From each examinee a blood sample was collected from which the levels of total plasma cholesterol (TC), triglycerides (TG), HDL-cholesterol (High Density Lipoprotein), LDL-cholesterol (Low Density Lipoprotein), lipoprotein Lp(a), and haemostatic risk factor fibrinogen (F) were determined. The detailed data were collected on the general knowledge and attitudes on health issues, followed by specific investigation of smoking history, alcohol consumption, nutrition habits, physical activity, family history of chronic non communicable diseases and occupational exposures. From the initial database a targeted sample of 5,840 persons of both sexes, aged 18-65, was created corresponding by age, sex and geographic distribution to the general Croatian population. This paper summarises and discusses the main findings of the project within this representative sample of Croatian population. PMID- 11787570 TI - West Nile virus activity--eastern United States, 2001. AB - In 2000, ArboNET, an enhanced human and animal surveillance system designed to monitor the geographic spread of West Nile virus (WNV) in the United States and to identify areas at increased risk for human infections with WNV, detected WNV activity in the District of Columbia and 12 states. This system, first implemented in the District of Columbia and 20 states along the Atlantic and Gulf coasts, was later expanded throughout the continental United States. This report summarizes ArboNET data from January 1 through July 25, 2001, which documents epizootic WNV activity in the southeast and indicates the need for widespread implementation of WNV prevention activities. PMID- 11787571 TI - Global progress toward laboratory containment of wild polioviruses, June 2001. AB - When the World Health Assembly resolved to eradicate poliomyelitis in 1988, the estimated number of polio cases was 350,000; in 2000, approximately 3000 cases were reported. Two World Health Organization (WHO) regions (the Americas and Western Pacific) have been certified as polio-free, and a third (European Region) has been free of indigenous wild poliovirus transmission for nearly 3 years (3 years are required for WHO certification). As interruption of wild poliovirus circulation approaches, public health agencies are increasing efforts to minimize the risk for reintroduction of wild polioviruses from laboratory sources. This report describes the global plan for containing laboratory wild polioviruses and summarizes the steps being taken toward implementation. PMID- 11787572 TI - Heat-related deaths--Los Angeles County, California, 1999-2000, and United States, 1979-1998. AB - Heat-related deaths typically occur during summer months. Many of these deaths are preventable. This report describes four cases of heat-related deaths in Los Angeles County, California, during 1999-2000, compares age-, sex-, and race specific rates in Los Angeles County and the United States during 1979-1998, and summarizes trends in the United States during 1979-1998. Relatives, neighbors, and caretakers of persons at risk for heat-related death should frequently evaluate heat-related hazards, recognize symptoms of heat-related morbidity, and take appropriate preventive action. PMID- 11787573 TI - National, state, and urban area vaccination coverage levels among children aged 19-35 months--United States, 2000. AB - Since the early 1970s, childhood vaccination has prevented millions of illnesses and tens of thousands of deaths. For these health benefits to continue, high levels of vaccination coverage must be attained for each new birth cohort and must be monitored to ensure protection from disease, to characterize undervaccinated populations, and to evaluate effortsto increase coverage. The National Immunization Survey (NIS) provides ongoing national estimates of vaccination coverage among preschool-aged children for the 50 states and 28 selected urban areas. For this report, NIS data collected during 2000 were compared with 1999 data; findings indicate that, during 2000, significant increases were reported on the national level of vaccination coverage with varicella and hepatitis B, and small but statistically significant decreases were reported in coverage with diphtheria, and tetanus toxoid, and pertussis vaccine. Coverage with poliovirus vaccine, Haemophilus influenzae type b vaccine, and measles-mumps-rubella vaccine were not significantly different from 1999. As in previous years, coverage varied among states. To maximize coverage among preschool-aged children, vaccination providers should continue to apply such strategies as reminders and recalls. PMID- 11787574 TI - Norwalk-like virus outbreaks at two summer camps--Wisconsin, June 2001. AB - On June 27 and 28, 2001, the Wisconsin Division of Public Health was notified by two local health departments of outbreaks of gastroenteritis at two summer recreational camps (camps A and B) in northern Wisconsin. This report summarizes the investigation of these outbreaks, which documents person-to-person transmission of "Norwalk-like virus" (NLV) and underscores the importance of cleaning environmental surfaces and the availability and use of hand-washing facilities at recreational camps. PMID- 11787575 TI - Fever, jaundice, and multiple organ system failure associated with 17D-derived yellow fever vaccination, 1996-2001. AB - At the June 2001 meeting of the Advisory Committee for Immunization Practices (ACIP), seven cases of multiple organ system failure (MOSF) in recipients of 17D derived yellow fever (YF) vaccine were presented. In response, an ACIP working group was formed to review the cases, assess the risk for serious adverse events following YF vaccination, and consider revision of the 1990 YF vaccination recommendations. This notice summarizes these cases and describes an enhanced surveillance program designed to refine risk estimates and improve histopathologic documentation of MOSF potentially associated with YF vaccination. PMID- 11787576 TI - Outbreaks of multidrug-resistant Salmonella typhimurium associated with veterinary facilities--Idaho, Minnesota, and Washington, 1999. AB - CDC received reports in 1999 from three state health departments of outbreaks of multidrug-resistant Salmonella serotype Typhimurium infections in employees and clients of small animal veterinary clinics and an animal shelter. Salmonella infections usually are acquired by eating contaminated food; however, direct contact with infected animals, including dogs and cats, also can result in exposure and infection. This report summarizes clinical and epidemiologic data about these outbreaks and reviews methods of reducing the likelihood of Salmonella transmission in veterinary settings by avoiding fecal-oral contact. PMID- 11787577 TI - Tularemia--Oklahoma, 2000. AB - In June 2000, seven cases of tularemia were reported to the Oklahoma State Department of Health (OSDH) over an 18-day period. Enhanced tularemia surveillance by OSDH during July-September 2000 detected four additional cases. During 1995-1999, an average of six cases were reported each year. This report summarizes clinical and epidemiologic information from the investigation of the 11 cases, presents three case reports to illustrate different risk factors for tularemia, and underscores the danger of delayed diagnosis of tularemia and the risk for acquiring tularemia in laboratory settings. Physicians should consider tularemia in ill persons with fever who reside in or visit areas where the disease is endemic and who have been exposed to ticks or carcasses or tissue from rabbits or other animals. PMID- 11787578 TI - Outbreak of pneumococcal pneumonia among unvaccinated residents of a nursing home -New Jersey, April 2001. AB - On April 24,2001, seven cases of pneumococcal pneumonia with bacteremia among residents of a nursing home were reported to the Hamilton Township Department of Health, New Jersey; all seven diagnoses were confirmed with blood cultures positive for Streptococcus pneumoniae. Illness onset among the residents occurred during April 3-24; four residents died. The New Jersey Department of Health and Senior Services (NJDHSS) was notified on April 24 and initiated an investigation to identify additional cases and implement control efforts. This report summarizes results of the investigation, which underscore the importance of providing pneumococcal polysaccharide vaccine (PPV) to elderly residents of long term care facilities (LTCFs). PMID- 11787579 TI - Adverse events and deaths associated with laboratory errors at a hospital- Pennsylvania, 2001. AB - On August 3, CDC was contacted by the Pennsylvania Department of Health (PADOH) to assist with an investigation of laboratory errors that may have contributed to the deaths of two persons taking the anticoagulant drug warfarin (Coumadin) (DuPont Pharmaceuticals Company, Wilmington, Delaware). The Food and Drug Administration (FDA) also is conducting an investigation of these incidents. Warfarin inhibits blood clotting and is prescribed for the management and prevention of conditions such as strokes, clots in the veins, and heart attacks. Physicians routinely monitor warfarin's anticoagulation effect on the blood by following two laboratory results: the prothrombin time (PT) and the International Normalized Ratio (INR). The INR is a numeric value calculated from the PT; the World Health Organization recommends the INR to standardize PT results from various manufacturers' devices and testing reagents. Physicians use INR to compare test results performed at different laboratories. PMID- 11787580 TI - Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001. AB - During February 12-August 24, 2001, a total of 21 cases of liver injury associated with a 2-month rifampin-pyrazinamide (RIF-PZA) regimen for the treatment of latent tuberculosis infection (LTBI) was reported to CDC. These 21 cases are in addition to two previously reported RIF-PZA-associated cases. Cases of liver injury have occurred each year since 1999. CDC also received reports of 10 cases associated with other LTBI treatment regimens; however, risk for liver injury cannot be compared among treatment regimens in part because the number of patients treated for LTBI with each treatment regimen is unknown. This report provides preliminary information about the 21 cases associated with RIF-PZA and the revised recommendations on selecting appropriate LTBI therapy for patients and monitoring the use of RIF-PZA to treat LTBI. In most instances, the 9-month isoniazid (INH) regimen is preferred for the treatment of patients with LTBI. RIF PZA may be used in selected cases and requires more intensive clinical and laboratory monitoring than previously recommended. PMID- 11787581 TI - Impact of targeted, school-based dental sealant programs in reducing racial and economic disparities in sealant prevalence among schoolchildren--Ohio, 1998-1999. AB - Despite the availability of highly effective measures for primary prevention, dental caries (tooth decay) remains one of the most common childhood chronic diseases. When properly placed, dental sealants are almost 100% effective in preventing caries on the chewing surfaces of first and second permanent molarteeth. However, sealants remain underused, particularly among children from low-income families and from racial/ethnic minority groups. Schools traditionally have been a setting for both dental disease prevention programs and for oral health status assessment. To determine the prevalence of dental sealant use among third grade students from schools with and without sealant programs, during the 1998-99 school year, the Ohio Department of Health conducted an oral health survey among schoolchildren. This report summarizes the results of this survey, which indicate that targeted, school-based dental sealant programs can substantially increase prevalence of dental sealants. Providing sealant programs in all eligible, high-risk schools could reduce or eliminate racial and economic disparities in the prevalence of dental sealants. PMID- 11787582 TI - Progress toward poliomyelitis eradication--South-East Asia, January 2000-June 2001. AB - Since the World Health Assembly resolved in 1988 to eradicate poliomyelitis globally, the estimated number of polio cases worldwide has declined 99%. During 1994, member countries of the South-East Asia Region (SEAR) of the World Health Organization (WHO) began accelerating efforts to eradicate polio. By 2000, wild poliovirus was detected in only four of the 10 countries: Bangladesh, India, Nepal, and Myanmar. This report summarizes polio eradication activities during January 2000-June 2001 in SEAR, where wild poliovirus transmission has declined rapidly and is occurring primarily in northern India. PMID- 11787583 TI - State-specific trends in high blood cholesterol awareness among persons screened- United States, 1991-1999. AB - High blood cholesterol (HBC) is a major risk factor for heart disease. One of the national health objectives for 2010 is to reduce the percentage of adults aged > or = 20 years with total blood cholesterol levels of > or = 240 mg/dL (objective 12-14). One strategy for achieving this objective is to increase awareness of HBC. State-specific data allow state health departments to monitor progress in educating the public about awareness of cholesterol levels and the need for persons to maintain low levels of blood cholesterol. To examine state-specific trends in the proportion of screened adults who reported that they were told that they had HBC, CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) for 1991 through 1999. This report summarizes the results of that analysis and indicates that approximately one fourth of screened survey participants were aware that they had HBC; this proportion increased slightly from 1991 through 1999. Awareness of HBC is a necessary step to help persons take action to lower their cholesterol level and their risk for coronary heart disease. PMID- 11787584 TI - Prevalence of healthy lifestyle characteristics--Michigan, 1998 and 2000. AB - Most persons with chronic diseases such as cardiovascular disease, cancer, diabetes, and chronic lung disease share multiple common risk factors and lifestyle behaviors. Tobacco use, poor diet, and physical inactivity have been identified as the leading contributors to overall mortality in the United States, accounting for one third of all deaths; Michigan has a particularly high burden of chronic disease-related mortality. To characterize the prevalence of four healthy lifestyle characteristics (HLCs) (i.e., healthy weight, adequate fruit and vegetable consumption, regular leisure-time physical activity [LTPA], and not smoking) in Michigan residents, data were analyzed from Michigan's Behavioral Risk Factor Surveillance System (BRFSS) for 1998 and 2000. This report summarizes the results of the analysis, which indicate that the proportion of Michigan residents who engaged in all four healthy lifestyle practices was extremely low, and that the prevalence was influenced by sex, education and self-reported health status. The comprehensive assessment of HLCs may be a useful adjunct to chronic disease surveillance. PMID- 11787585 TI - Outbreak of Powassan encephalitis--Maine and Vermont, 1999-2001. AB - Powassan (POW) virus, a North American tickborne flavivirus related to the Eastern Hemisphere's tickborne encephalitis viruses, was first isolated from a patient with encephalitis in 1958. During 1958-1998, 27 human POW encephalitis cases were reported from Canada and the northeastern United States. During September 1999-July 2001, four Maine and Vermont residents with encephalitis were found to be infected with POW virus. These persons were tested for other arbovirus infections found in the northeast after testing for West Nile virus (WNV) infection was negative. This report describes these four cases, summarizes the results of ecologic investigations, and discusses a potential association between ticks that infest medium-sized mammals and the risk for human exposure to POW virus. The findings underscore the need for personal protective measures to prevent tick bites and continued encephalitis surveillance. PMID- 11787586 TI - Expanding the circle 1975-1999: sulfur biochemistry and insights on the biological functions of taurine. PMID- 11787587 TI - Taurine prevents ischemia damage in cultured neonatal rat cardiomyocytes. PMID- 11787588 TI - Effects of taurine and thiosulfate on the spectrophotometric properties of RNA and DNA. PMID- 11787589 TI - Ionomycin restores taurine transporter activity in cyclosporin-A treated macrophages. AB - Taurine is accumulated at high concentrations in various tissues. The taurine transporter (TAUT) is responsible for the transportation of taurine in the cell. The transporter is affected by various stimuli to maintain cell volume. Macrophage cell volume varies in its activated states. In our experiment, it was found that the murine macrophage cell line, RAW264.7, expressed TAUT protein in its membrane. Its transporting activities could be blocked by beta-amino acid such as beta-alanine, but not by alpha-amino acids in this cell line, when assessed in RAW264.7 cells under the influence of immunosuppressive reagents, the activity of the TAUT was decreased by treatment with rapamycin (RM) or cyclosporin A (CSA). However, when ionomycin (IM) was added to this system, TAUT activity was recovered only in CSA-treated cells, in a concentration-dependent manner, in order to inhibit voltage gated Ca2+ channels, calmidazolium was added to the RAW264.7 cell line. Treatment of the cells with calmidazolium completely blocked TAUT. Furthermore, addition of IM to this system resulted in recovery the activity of TAUT again. When we added phorbol myristyl acetate (PMA) to the cell line, secretion of nitric oxide (NO) was increased 4-fold and the TAUT activity was decreased 5-fold. However, the addition of N-nitro L-arginine methyl ester (L NAME), an inducible NO synthase (iNOS) inhibitor, to the PMA-treated cells induced recovery of TAUT activity. These results showed that the activity of TAUT was sensitive to both the intracellular concentrations of Ca2+ and NO. PMID- 11787590 TI - Daily dietary taurine intake in Japan. PMID- 11787591 TI - Comparative studies on serum taurine and plasma fatty acids in humans between the sea side area in Toyama, Japan and the mountain areas in Inner Mongolia, China. PMID- 11787592 TI - Biochemical and ultrastructural alterations in rat after hyperoxic treatment: effect of taurine and hypotaurine. AB - The cell ultrastructure and some detoxifying enzyme activities were studied in skeletal muscles of young rats kept for 84 h under normobaric hyperoxia (95% O2) or normoxia as control. Rat were injected i.p.. Every 12 h either with 1 ml saline, 1 ml saline+30 mg hypotaurine or 1 ml saline+30 mg taurine. Ultrastructural observation revealed an highly protective effect on tissue damages due to hyperoxia in taurine-treated rats and, at less extent, in hypotaurine-treated ones. Enzymatic assays suggest a different mechanism of the two molecules in their protective action. PMID- 11787593 TI - Hypotaurine protection on cell damage by singlet oxygen. AB - Singlet oxygen (1O2), generated by irradiating methylene blue, is toxic to melanoma cell cultures. Hypotaurine is known to scavenge efficiently singlet oxygen; the addition of hypotaurine (800 microM) to the medium during irradiation of the dye produces a greater protective effect on cells than taurine added at the same concentration. The assay of some detoxifying enzymatic activities indicate a different mechanism of protection of the two molecules: taurine induces an efficient detoxifying enzymatic action with respect to the control; hypotaurine exerts its effect greatly by specifically scavenging singlet oxygen. PMID- 11787594 TI - Hypotaurine and superoxide dismutase: protection of the enzyme against inactivation by hydrogen peroxide and peroxidation to taurine. AB - Hypotaurine is able to prevent the inactivation of SOD by H2O2. The protection is concentration-dependent: at 20 mM hypotaurine the inactivation of SOD is completely prevented. It is likely that hypotaurine exerts this effect by reacting with hydroxyl radicals, generated during the inactivation process, in competition with the sensitive group on the active site of the enzyme. According to this, spectral studies indicate that in presence of hypotaurine the integrity of the active site of SOD is preserved by the disruptive action of H2O2. An interesting outcome of the SOD/H2O2/hypotaurine interaction is that SOD catalyzes the peroxidation of hypotaurine to taurine. Indeed, the formation of taurine increases with the reaction time and with the enzyme concentration. Although the peroxidase activity of SOD is not specific and relatively slow compared to the dismutation of superoxide, it might represent another valuable mechanism of production of taurine. PMID- 11787595 TI - Dietary taurine changes ascorbic acid metabolism and cholesterol metabolism in rats fed diets containing polychlorinated biphenyls. PMID- 11787596 TI - Effects of long-term treatment with taurine in mice fed a high-fat diet: improvement in cholesterol metabolism and vascular lipid accumulation by taurine. AB - Hypocholesterolemic effects of taurine in rats fed a high-fat and high cholesterol diet are well established. However, there are few studies on long term effects of taurine on cholesterol metabolism. In the present study, taurine was dissolved in drinking water and given to C57BL/6J mice during 6 months feeding of a high fat diet. Taurine treatment significantly decreased serum LDL and VLDL cholesterol, while it significantly increased serum HDL cholesterol. In the liver, taurine decreased cholesteryl ester contents, accompanied by decrease in acyl CoA:cholesterol acyltransferase (ACAT) activity. Hepatic activity of cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, was doubled with taurine. Taurine reduced by 20% the high-fat diet-induced arterial lipid accumulation. Thus, taurine prevented elevation of serum and liver cholesterol levels, as possibly related to accelerated cholesterol elimination from the body through the stimulation of bile acid synthesis. Long-term treatment with taurine is beneficial for prevention of hypercholesterolemia and atherosclerosis. PMID- 11787597 TI - Hypolipidemic effect of taurine in golden Syrian hamsters. PMID- 11787598 TI - Taurine reduces atherosclerotic lesion development in apolipoprotein E-deficient mice. AB - The effects of dietary taurine on development of atherosclerotic lesions were investigated using apolipoprotein E (apoE)-deficient mice. Taurine added to regular chow at 2% (w/w), was made freely available to mice for 3 months. Severe hypercholesterolemia and development of atherosclerotic lesions occurred in the apo-E-deficient mice. Taurine treatment decreased the area of Oil red-O positive lipid accumulation in the aortic valve by 31%. In contrast, taurine significantly increased serum atherogenic lipoproteins (LDL + VLDL), without changing HDL cholesterol levels. Although the levels of serum thiobarbituric acid reactive substances (TBARS) in apoE-deficient mice were significantly higher than in wild type mice, taurine decreased TBARS by 26%. These observations mean that taurine prevents the development of atherosclerosis, independent of serum cholesterol levels. We suggest that antioxidative actions may be involved in the anti atherosclerotic effects of taurine. PMID- 11787599 TI - Does taurine play an osmolarity role during ethanol intoxication? PMID- 11787601 TI - Isovolumic regulation in nervous tissue: a novel mechanism of cell volume regulation. PMID- 11787600 TI - Osmotic sensitivity of taurine release from hippocampal neuronal and glial cells. AB - Taurine transport is important for volume regulation of cultured neurons and astroglial cells. Both cell types utilize similar mechanisms for taurine accumulation and efflux. However, taurine lost from cerebellar Purkinje cells in vivo is accumulated by adjacent astrocytes during hypoosmotic hyponatremia. To examine mechanisms for transfer of taurine between cell types, we measured relative sensitivities of taurine loss from cultured neurons and astrocytes. Primary cultures of hippocampal neurons and astrocytes were grown from embryonic and neonatal rat brain, respectively. Neurons were used after 10-14 days in culture. Astrocytes were used after 14 days in culture and were grown in the same culture medium used for neurons for 3 days prior to experimentation. Cells were incubated at 37 degrees C for 30 min in isoosmotic (290 mOsm) phosphate-buffered saline (PBS). The PBS was then changed to fresh isoosmotic or to hypoosmotic PBS (270 mOsm or 250 mOsm), made by reducing the NaCl concentration. Cell volume and taurine content were determined immediately before hypoosmotic exposure or 3, 15, or 30 min later. In isoosmotic PBS, astrocytes contained 162 +/- 18 nmol taurine/mg protein (mean +/- SEM), equivalent to an intracellular concentration of 30.2 +/- 2.1 mM. No taurine loss was detectable after 3 or 15 min in either hypoosmotic PBS, but after 30 min in 270 or 250 mOsm PBS, astrocyte taurine was reduced by 8.0% or 22.2%, respectively. Neurons initially contained 114 +/- 13 nmol taurine/mg protein, equivalent to an intracellular taurine concentration of 22.2 +/- 2.5 mM. After 3 min of exposure to 270 or 250 mOsm PBS, the cells had lost 17 +/- 5% or 25 +/- 4% of their taurine content, respectively. Cell volumes of each cell type were similarly affected by hypoosmotic exposure. We conclude that taurine loss from cultured hippocampal neurons is more sensitive to osmotic swelling than taurine loss from cultured hippocampal astrocytes. This characteristic, if present in cells of the hippocampus in vivo, could lead to net transfer of taurine from neurons to glial cells during pathological conditions which cause cell swelling. PMID- 11787602 TI - New role of taurine as an osmomediator between glial cells and neurons in the rat supraoptic nucleus. PMID- 11787603 TI - Gene expression of taurine transporter and taurine biosynthetic enzymes in hyperosmotic states: a comparative study with the expression of the genes involved in the accumulation of other osmolytes. PMID- 11787604 TI - Involvement of ion channels in ischemia-induced taurine release in the mouse hippocampus. PMID- 11787605 TI - Modulation of taurine release by metabotropic receptors in the developing hippocampus. PMID- 11787606 TI - Extracellular taurine as a parameter to monitor cerebral insults 'on-line': time courses and mechanisms as studied in vivo. AB - Taurine increases in the zone surrounding a thrombotic infarct which could be prevented by a neuroprotective drug. Therefore, we aimed at studying the possible release mechanisms since the monitoring of taurine might give valuable information on the progress of cerebral insults and the effect of drugs. A microdialysis membrane was implanted into the cortex of anaesthetised rats: As toxic triggers possibly released by the dying cells in the peri-infarct zone, either a glutamatergic agonist (NMDA) or high potassium were applied via the microdialysis probe. Alternatively, a diluted perfusate was applied to induce cell swelling directly. NMDA antagonists or the NO synthase inhibitor L-NAME were applied locally too. NMDA, NO, high potassium or the hypotonic solution stimulated the release of taurine. The effect of high potassium could be prevented by Ketamine, but not by APV. The effect of NMDA could be inhibited by APV or Ketamine or the NO synthase inhibitor L-NAME. The release of taurine induced by the hypotonic solution could not be be reduced by any of the inhibitors. These data suggest that the release of taurine induced by glutamatergic activity is mediated via the NO cascade. The potassium mediated release seems to be related only in part to glutamatergic activity. Thus, other mechanisms seem to be predominate in potassium mediated swelling. Hypoosmotically induced taurine release is not mediated via the NO cascade and also seems to differ from the aforementioned release mechanisms. IN CONCLUSION: Monitoring of extracellular taurine allows to follow pathological events and to differentiate drug effects. PMID- 11787607 TI - Professor Doriano Cavallini: a life for sulfur biochemistry. PMID- 11787608 TI - Effects of taurine and some structurally related analogues on the central mechanism of thermoregulation: a structure-activity relationship study. AB - There is large body of evidences on the role of taurine in the central mechanisms of thermoregulation in mammals, but it is not clear, whether the hypothermic effect of taurine depends on its interaction with GABA receptors or with a specific receptor. In order to answer this question, we have performed a structure-activity relationship study by using both in vitro and in vivo preparations. MicroM amounts of taurine or each of 20 analogues were injected intracerebroventricularly in conscious, restrained rabbits while rectal temperature was recorded. Receptor-binding studies, with synaptic membrane preparations from rabbit brain were used to determine the affinities of these compounds for GABA(A) and GABA(B) receptors. Furthermore, the interaction with presynaptic GABA and taurine uptake systems was studied using crude synaptosomal preparations from rabbit brain. Among the compounds tested, (+/-)-cis-2 aminocyclohexanesulfonic acid, induced hypothermia, but did not interact with GABA(A) and GABA(B) receptors neither did it affect GABA and taurine uptake, thus suggesting that its effect on body temperature is not mediated by the central GABAergic system. Interestingly, the trans-isomer was devoid of effects either in vivo or in vitro. In order to explain (+/-)-cis-2-aminocyclohexanesulfonic acid induced hypothermia, a stereoscopic model was produced showing its possible interactions with a putative taurine brain receptor. PMID- 11787609 TI - Taurine-induced synaptic potentiation: dependence on extra- and intracellular calcium sources. PMID- 11787610 TI - The effect of kainic acid and AMPA on the release of taurine and GABA from the rat substantia nigra in vivo. PMID- 11787611 TI - Effects of ethanol and glutamate agonist infusion on the outflow of sulphoacetaldehyde: microdialysis studies. PMID- 11787612 TI - Taurine, glutamine, glutamate, and aspartate content and efflux, and cell volume of cerebrocortical minislices of rats with hepatic encephalopathy: influence of ammonia. PMID- 11787613 TI - Professor Alberto Giotti: a father of taurine research. PMID- 11787614 TI - The effect of taurine derivative on lipid peroxidation and interhemispheric asymmetry of phospholipids from the brain synaptosomes in rats after immobilization stress. AB - Malondialdehyde (MDA) as an indicator of lipid peroxidation (LPO), content and composition of phospholipids (PL) were analyzed in synaptosomes of the rat brain hemispheres using immobilization stress without and with pretreatment with a new synthetic taurine derivative (STD). The stress was accompanied by a decrease MDA content, inversion of the initial asymmetry of total phospholipids (TPL) and modification PL composition in the brain hemispheres of rats. STD administration to the rats after stress antagonized the decrease of the MDA level, attenuates stress induced inversion TPL asymmetry and normalized PL composition in the brain hemispheres. Prevention or diminution of synaptosomal PL changes in the rat brain hemispheres are interpreted as one of the possible mechanisms of the neuroprotective effect of STD. PMID- 11787615 TI - Taurine transport mechanism through the blood-brain barrier in spontaneously hypertensive rats. AB - Taurine levels in the brain decrease when an animal is subjected to pathological conditions, such as ischemia-anoxia and seizure, but they tend to increase in hypertension. The present study investigated the blood-brain barrier (BBB) transport of [3H]-labelled taurine in spontaneously hypertensive rats (SHR) using internal artery carotid perfusion (ICAP) at a rate of 4 ml/min for 10, 15 and 30 seconds. The volume of distribution in brain (VD) and the permeability surface area product (PS) of [3H]-taurine through the BBB in SHR were calculated. The PS value for taurine at 15 s was higher than at the longer perfusion times. This could result from taurine efflux back into blood occurring after 15 s. As in the case of normotensive rats, taurine was shown to enter the brain via the sodium and chloride ion dependent carrier system. PMID- 11787616 TI - Protection of intrinsic nerves of guinea-pig detrusor strips against anoxia/glucopenia and reperfusion injury by taurine. AB - There is ample evidence that ischaemia is associated with partial denervation of the detrusor muscle and that this is responsible for much of its abnormal contractile behaviour, resulting in bladder dysfunction (instability). In guinea pig nerves are very susceptible to the ischaemic damage as compared to the muscle cells. The purpose of this study was to assess the neuroprotection afforded by taurine on guinea-pig detrusor under ischaemic-like conditions. Guinea-pig detrusor strips were subjected for 60 min to ischaemic-like conditions, followed by 150 min reperfusion. Intrinsic nerves underwent every 30 min electrical field stimulation (EFS) by 5-s trains of square voltage pulses of 0.05 ms duration (15 Hz, 50 V). Detrusor strips were perfused with 0.1, 1, 3 or 10 mM taurine during the ischaemia-like exposure and the first 30 min of reperfusion. Taurine (1 and 3 mM) significantly improved the response of the strips to EFS both at the end of ischaemia and reperfusion. On the contrary, neither 0.1 nor 10 mM taurine had significant effects. It is concluded that taurine can partially counteract the ischaemia-reperfusion injury in the guinea-pig urinary bladder. PMID- 11787617 TI - The possible role of taurine and GABA as endogenous cryogens in the rabbit: changes in CSF levels in heat-stress. AB - We investigated whether heat-stress induced hyperthermia could enhance release of both endogenous taurine and GABA from nerve cells into the extracellular compartment, thus acting like endogenous cryogens. Conscious rabbits were exposed for 1 hr to 40 degrees C (heat stress) while cerebrospinal fluid (CSF) and plasma osmolality and the CSF concentrations of some cations, proteins as well as those of taurine and GABA were determined. Heat stress-induced hyperthermia was accompanied by a significant rise in CSF and plasma osmolality, CSF calcium, taurine and GABA levels. It is suggested that during heat stress taurine and GABA are released in the extracellular space of brain tissues in higher amounts, as compared to control conditions, to counteract the resulting hyperthermia, thus acting as cryogenic agents. PMID- 11787618 TI - Interaction of taurine with metal ions. PMID- 11787619 TI - Mode of action of taurine and regulation dynamics of its synthesis in the CNS. PMID- 11787620 TI - Attenuation of oxidative damage to DNA by taurine and taurine analogs. AB - Taurine has been suggested to have cytoprotective actions via a number of different mechanisms. The role of taurine in protecting DNA from oxidative damage has received only limited attention. The aim of the present studies was to test the hypothesis that taurine might act to attenuate oxidative damage to DNA caused by free radicals generated by iron-stimulated catecholamine oxidation in the presence of H2O2. Calf thymus DNA (100 microg/tube) was exposed to a reaction mixture containing: ferric chloride (60 microM), H2O2 (2.8 mM) and L-dopa (100 microM). Taurine and taurine analogs were added simultaneously to determine their effects to prevent oxidative damage to DNA. The reaction was carried out for 1 hour at 37 degrees C and terminated by rapid freezing in an ethanol/dry ice bath. The DNA was precipitated with ethanol and subsequently hydrolyzed with formic acid under vacuum. The hydroxylated bases were separated by HPLC and detected electrochemically. All experiments were replicated a minimum of 5 times. Taurine (20 mM) was found to reduce (p<0.05) damage to DNA as indexed by reductions in the formation of 5-OH-uracil (49% decrease), 8-OH adenine (37% decrease), and 8 OH guanine (21% decrease). Taurine had minimal effects to reduce the formation of 5-OH cytosine (<7% decrease). Taurine (20 mM) also increased total DNA recovery after damage 36-40% and increased total undamaged guanine approximately 32%. 5-OH Uracil formation could be reduced (p<0.05) by 1 mM taurine and 8-OH-adenine formation was reduced (p<0.05) by 5 mM taurine. Studies were conducted with various amino acid analogs and total base adduct formation was reduced by 20 mM beta-alanine (30% decrease), lysine (58% decrease) and glutathione (88% decrease). When tested at 20 mM, both hypotaurine and homotaurine provided greater protection against DNA damage than taurine, whereas isethionic acid provided a similar level of protection as taurine. Using identical conditions as the assays for base hydroxylation, we tested whether inhibition of quinone formation could account for taurine's mechanism of action. Taurine (49% decrease), homotaurine (24% decrease) and hypotaurine (79% decrease) all reduced quinone formation. Thus, inhibition of quinone formation could account for part of taurine's mechanism of action to inhibit oxidative damage, but it could not account for homotaurine's greater efficacy in preventing DNA damage. Overall, these studies show that taurine at concentrations normally found in cells can inhibit oxidative damage to DNA. PMID- 11787621 TI - Tyrosine-hydroxylase immunoreactive cells in the rat striatum following treatment with MPP+. AB - Tyrosine Hydroxylase is the rate-limiting enzyme in the synthesis of dopamine, and as such, it is widely used as a marker of dopaminergic cells. Within the basal ganglia, the dopaminergic cells are located in the substantia nigra pars compacta, and project to the striatum. It is this pathway which degenerates during Parkinson's disease. The data presented here illustrate examples of tyrosine-hydroxylase immunoreactive cells in striatum following intrastriatal injection with the neurotoxin MPP+. We further show by electron microscopy that these cells are, in fact, neurons and that they possess ultrastructural features of interneurons. PMID- 11787622 TI - Investigation of the therapeutic efficacy of a taurine analogue during the initial stages of ethanol detoxification: preliminary studies in chronic alcohol abusers. PMID- 11787623 TI - Metabolism of taurine to sulphoacetaldehyde during oxidative stress. PMID- 11787624 TI - Taurine chloramine attenuates the hydrolytic activity of matrix metalloproteinase 9 in LPS-activated murine peritoneal macrophages. PMID- 11787625 TI - Synthesis of taurine analogues from alkenes: preparation of 2 aminocycloalkanesulfonic acids. AB - (+/-)trans 2-Aminocyclohexanesulfonic acid and (+/-)trans 2 aminocyclopentanesulfonic acid were prepared from cyclohexene and cyclopentene respectively by sulfur monochloride addition, followed by oxidation to 2 chlorosulfonic acid and substitution of chlorine. PMID- 11787626 TI - Effects of guandinoethane sulfonate on contraction of skeletal muscle. AB - Guanidinoethane sulfonic acid (GES), a chemical and biological analog of taurine, decreases rat muscle taurine content when added to drinking water. Over the same period, GES appears in muscle. GES supplementation is often used to study the effect of taurine depletion on physiological mechanisms, without taking into account the possible actions of GES. The purpose of the present study was to investigate the specific actions of GES on contraction of skeletal muscle. In mice EDL muscle, the time delay needed to observe a 20% force decrease after the end of a tetanic stimulation was higher in GES-supplemented than in control muscle. This observation in GES-supplemented muscle could be explained by the action of taurine or GES on several targets, beside others the rate of Ca2+ uptake by sarcoplasmic reticulum (SR) and the Ca2+ sensitivity of myofilaments. SR of rat EDL was isolated by successive centrifugations. The effect of 20 mM taurine or GES on the rate of Ca2+ uptake by SR was measured with the fluorescent Ca2+ indicator fura-2. The results show that the rate of Ca2+ uptake by SR is not modified in the presence of taurine or GES. The Ca2+ sensitivity of myofilaments was studied in chemically skinned fibers in the presence of 20 mM taurine or GES. Both taurine and GES increased the myofilament sensitivity to Ca2+. Thus, the prolonged relaxation time of GES-supplemented muscle can be attributed to an increase in myofilament sensitivity to Ca2+. This higher sensitivity is not due to a decrease in muscle taurine content but rather to an increased GES concentration. PMID- 11787627 TI - Protection by taurine and structurally related sulfur-containing compounds against erythrocyte membrane damage by hydrogen peroxide. PMID- 11787628 TI - Regulation of high affinity taurine transport in goldfish and rat retinal cells. AB - Adaptive regulation and modulation by phosphorylation are mechanisms by which some cells control taurine transport. Goldfish and rat retinal cells were incubated with the activator of protein kinase C, phorbol 12,13-dibutyrate (PDBu), or the inhibitor of protein phosphatases, okadaic acid (OKA). OKA, 1 nM, inhibited the uptake of taurine at short period of incubation in goldfish retinal cells, and at low concentrations in rat retinal cells incubated with the inhibitor for 1 h. PDBu treatment did not produce significant effects. Isolated Muller cells from the goldfish retina presented a clear adaptive regulation and a decrease of taurine uptake by increasing phosphorylation either by the stimulation of PKC with PDBu or the inhibition of phosphatases with OKA. PMID- 11787629 TI - Effects of osmotic and light stimulation on 3H-taurine efflux from isolated rod outer segments and synthesis of tauret in the frog retina. AB - After injection of 3H-taurine into eyeballs of frogs and maintenance for 3 h in darkness by a gentle shaking, an almost homogenous fraction of rod outer segments (ROS) was prepared. About a 22% decrease in tonicity caused by reducing NaCl in isotonic 225 mOsm normal solution caused a rapid increase in the rate coefficient of efflux of 3H-taurine from the ROS fraction. The peak level of increased efflux rate coefficient was 7-times higher than the basal isotonic level. This indicates that taurine could contribute essentially to the volume regulation, either via selective channels or a carrier transporter-mediated pathways. For further clarifying if taurine fluxes in the ROS are sensitive to the light, other experiments were performed. Neither light stimulation of dark-adapted ROSs fractions or dark stimulation of weakly illuminated ROSs revealed any detectable changes in the efflux rate coefficient of 3H-taurine. These results indicate that light-induced taurine efflux, if present in the ROS, must be small, compared with hypoosmotic induced efflux. Thus the question of light-induced release of taurine from ROS still remains to be clarified. In the second part of this study, using TLC (thin layer chromatography) in combination with 3H-taurine measurements we have tried to clarify whether frogs (Rana ridibunda) eye structures can synthesize tauret (retinylidenetaurine). In isolated retinal preparations almost no any noticeable radioactivity was detected compared with background level. The capability of the eye structures to synthesize tauret from 3H-taurine was revealed in the second whole eye injection experiment. About 0.3% of the total 3H taurine pool taken up was converted into 3H-tauret in the dark-adapted frog retina. In the retina of frogs adapted to light compared with those which were dark adapted tauret quantities were remarkable lower--on average about half. These results are in agreement with our recent data obtained by HPLC, which indicate tauret levels several times higher in the dark-adapted frog retinae compared with those after long lasting light adaption. Taking into account these results one can conclude that the main structure able to synthesize 3H-tauret is probably pigment epithelium rather than retina. PMID- 11787630 TI - Taurine and skeletal muscle ion channels. PMID- 11787632 TI - Characterization of taurine uptake in the rat retina. PMID- 11787631 TI - New HPLC evidence on endogenous tauret in retina and pigment epithelium. AB - This investigation was improve the separation for tauret (retinylidene taurine) and to compare its content in the retina under dark and light adaptation. To prevent tauret hydrolysis, retinal samples were quickly frozen and lyophilized. Methanol extracts of dried retina and pigment epithelium from both dark- or light adapted frogs, Rana ridibunda, were injected onto HPLC. Synthetic standard tauret appeared at 4.7 min after the solvent front. At the same time, an endogenous substance was eluted from the mixed retinal and pigment epithelial samples. The UV spectra of this endogenous compound matched with the spectra of synthetic tauret obtained under identical conditions, with lambda(max) = 446 nm at peak. We conclude that the HPLC system used permitted full separation of tauret from the methanol extracts of the retina and pigment epithelium. TLC and further HPLC analysis have shown that tauret quantities were several times higher in the retina and pigment epithelium of the frogs adapted to dark compared with those light-adapted (about 4 h under 1000 1x illumination). Tauret based vitamin A transport is probably involved in other systems as well, where along with its other known beneficial effects taurine probably is necessary to facilitate vitamin A transport. PMID- 11787633 TI - Calcium uptake in the rat retina is dependent on the function of the cyclic nucleotide-gated channel: pharmacologic evidence. PMID- 11787634 TI - Effects of calmodulin antagonists on taurine-stimulated calcium ion uptake in the rat retina are partly independent of calmodulin activity. PMID- 11787635 TI - Swelling-induced taurine efflux from HeLa cells: cell volume regulation. PMID- 11787636 TI - Taurine fluxes in insulin dependent diabetes mellitus and rehydration in streptozotocin treated rats. AB - The effect of streptozotocin induced diabetes mellitus and rehydration on brain taurine and brain water content was studied in 4 groups of rats. Two groups of rats with diabetes mellitus were used. In one group, taurine and brain water content were determined following induction of diabetes for one week. In the second group, diabetes was induced for one week but before sacrifice, 15% of body weight of normal saline was introduced into the peritoneum, half at time 0, half 30 minutes later with sacrifice 60 minutes after the first infusion. In two groups of animals (controls), the brain taurine and water content were estimated in normal conditions and after hydration, in exactly the same way as diabetic rats. Brain taurine content was greater in diabetic rats than non-diabetic rats and there was no decrease in brain taurine content within the first hour following rehydration of the diabetic rats. Brain water content was greater in rehydrated diabetic rats than in non-rehydrated diabetic rats but there was no significant change in the brain water content after hydration of non diabetic rats. This suggested that the rapid change in water content of rehydrated diabetic rats was not accompanied by an equally rapid alteration in brain taurine content. This is consistent with the hypothesis that taurine flux could be a major factor in the aetiology of diabetic cerebral oedema. It also allows the development of possible therapeutic options which may increase outward taurine flux from brain cells. Taurine flux is increased by increasing extracellular sodium concentration or decreasing potassium concentration. Phospholemman channels may also influence taurine flux. These may have implications for the optimal method of clinical rehydration undertaken in diabetic ketoacidosis. PMID- 11787637 TI - In vitro and in vivo effects of taurine and structurally related sulfur containing compounds against phenylhydrazine-induced oxidative damage to erythrocytes. PMID- 11787638 TI - A taurine transporter isolated from rat cardiac muscle. PMID- 11787639 TI - Identification of promoter elements involved in adaptive regulation of the taurine transporter gene: role of cytosolic Ca2+ signaling. PMID- 11787640 TI - Suppression of bleomycin-induced increased production of nitric oxide and NF-kB activation by treatment with taurine and niacin. PMID- 11787641 TI - Cytoprotective effect of taurine against hypochlorous acid toxicity to PC12 cells. AB - Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCl). The role of HOCl is well established in tissue damage associated with reperfusion injury mediated by neutrophils. The role of HOCl in CNS injury and inflammatory reactions has not been well established. Myeloperoxidase activity is present in the CNS and it has been associated with ischemic injury. The aim of the present study was to determine the cytotoxicity of HOCl in a neuronal cell line (PC12) and the ability of taurine to prevent or reverse neurotoxicity. PC12 cells were grown in 96 well plates at a plating density of approximately 100,000 cells per well. HOCl was made up fresh from NaOCl for each experiment and the concentration verified spectrophotometrically. PC12 cells were exposed to HOCl for 1 hour in phosphate-buffered saline. Taurine was added at the time of HOCl treatment and in some experiments a post-treatment with taurine was performed by adding 1 or 10 mM taurine to the culture media (RPMI 1640). The cells were allowed 24 hours to recover and viability was determined using a tetrazolium-based (MTT) assay. The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect PC12 cells. HOCl at 50 microM reduced PC12 cell viability by 50% and 150 microM reduced viability to <25% of control levels. Taurine (0.5-20 mM) was tested for cytoprotection against 150 microM HOCl and PC12 cells treated with 0.5 mM taurine exhibited only a 20% reduction in viability compared to untreated controls. Taurine concentrations of 1 mM or higher provided nearly 100% protection against HOCl. A second study was performed comparing taurine to beta alanine, glutathione and isethionic acid. HOCl (100 microM) reduced viability to 25 +/- 1% of controls and taurine, beta-alanine and glutathione at 1 mM provided nearly complete protection. In contrast, isethionic acid, which lacks an amino group, failed to provide protection. Taurine (1 or 10 mM) added after 50 microM HOCl treatment did not provide any protection and PC12 cell viability was reduced to <39% of controls. In contrast, if taurine (50 microM) was present during the HOCl treatment and 1 mM taurine was added after the treatment, PC12 cell viability was 80 +/- 5% of controls. A combination of 250 microM taurine during the HOCl treatment and 1 mM taurine post-treatment produced 100% protection. These results clearly show that taurine is an efficient scavenger of HOCl and can prevent neuronal damage caused by HOCl. Since myeloperoxidase expression in the CNS is increased by ischemia, one function of taurine released during an ischemic event may be to scavenge HOCl and provide neuroprotection. PMID- 11787642 TI - Taurine-deficient cardiomyopathy: role of phospholipids, calcium and osmotic stress. PMID- 11787643 TI - Effect of taurine and beta-alanine on morphological changes of pancreas in streptozotocin-induced rats. AB - In order to determine the effects of taurine supplementation or depletion on the morphological changes of pancreatic beta-cells in streptozotocin-induced diabetic rats, Sprague-Dawley male rats were fed the purified diets supplemented with 1, 2 or 3% taurine or 5% beta-alanine in their drinking water for 7 weeks. After 3 weeks, diabetes was induced by streptozotocin injection (50 mg/kg body-weight). Pancreatic morphology was observed by transmission electron microscopy. The pancreatic beta-cell of the non-diabetic (CO) group had the many secretory granules, rough endoplasmic reticulum and rod shaped mitochondria. However, the beta-cells of non taurine-supplemented diabetic (EO) group were severely damaged, showing depleted secretory granules. In the 1% taurine-supplemented diabetic group, the beta-cells were less damaged compared to the EO group and had some apparently normal secretory granules, but most of rough endoplasmic reticulum and mitochondria was destroyed. The beta-cell of 2% taurine-supplemented diabetic group had swollen rough endoplasmic reticulum, round-shaped mitochondria and some apparently normal secretory granules. The beta-cell of 3% taurine-supplemented diabetic group was little different from that of non-diabetic group. The pancreatic beta-cell of taurine-depleted diabetic group was not destroyed but had many small secretory granules which appeared immature. This was reflected in the blood glucose concentrations of this group. Therefore, taurine may prevent insulin-dependent diabetes by protection of the pancreatic beta-cell and may also preserve normal secretory granules. From these results, taurine supplementation may be recommended for prevention and treatment of diabetes. PMID- 11787644 TI - Immunohistochemical localization of insulin in pancreatic beta-cells of taurine supplemented or taurine-depleted diabetic rats. AB - The purpose of this study was to observe the effects of taurine supplementation or depletion on the immunohistochemical localization of insulin in pancreas of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were fed for 7 weeks with a purified diet that was supplemented with 0, 1, 2 or 3% taurine in their drinking water. To induce taurine depletion, rats were treated with 5% beta alanine in their drinking water. After 3 weeks, diabetes was induced by streptozotocin injection (50 mg/kg body-weight). The pancreatic tissue was stained immunocytochemically, using an antibody to insulin, and examined by light microscopy. The insulin levels in pancreatic beta-cells of the diabetic group that received no taurine-supplement were significantly decreased, compared to the non-diabetic group. The levels of insulin in beta-cell of 1% and 2% taurine supplemented diabetic groups were significantly higher than those of the diabetic group, whereas the levels in the group receiving 3% taurine were not significantly different from that of non-diabetic rats. Therefore, it may be suggested that taurine protect pancreatic beta-cells against destruction by ptozotocin injection in a dose-dependent way. PMID- 11787645 TI - Taurine attenuates the induction of immediate-early gene expression by PDGF-BB. PMID- 11787647 TI - Taurine intake and excretion in patients undergoing long term enteral nutrition. AB - The purpose of this study was to investigate whether serum concentration and urinary excretion of taurine are influenced by marginal taurine intake. Twenty one male patients (75 to 95 years old), suffering from coronary heart disease, multiple cerebral infarction, cancer, subdural hematoma or respiratory failure were grouped according to duration of tube feeding (group one, 5.9 +/- 2.9; group two, 14.8 +/- 2.3; group three 48.0 +/- 22.7, mean +/- SD, months). The mean intake of taurine was 347.0 +/- 25.6, 339.8 +/- 25.6 and 337.1 +/- 259 micromol/day (mean +/- SEM) in group one, two and three, respectively. The fasting serum taurine levels were 106.5 +/- 9.6, 95.0 +/- 9.9 and 56.8 +/- 11.0 micromol/L (mean +/- SEM) in group one, two and three, respectively. Taurine level in group three patients was significantly lower than that of group one and two (p<0.05). The twenty-four hour urinary taurine excretion was 776.1 +/- 176.7, 782.4 +/- 245.3 and 388.3 +/- 169.3 micromol/day (mean +/- SEM) in group one, two and three, respectively. These results suggest that marginal taurine intake in patients receiving long term tube feeding could result in taurine deficiency. PMID- 11787646 TI - Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study. AB - Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage. PMID- 11787648 TI - Does the taurine transporter gene play a role in 3p-syndrome? PMID- 11787649 TI - Extracellular levels of taurine in tumoral, peritumoral and normal brain tissue in patients with malignant glioma: an intraoperative microdialysis study. PMID- 11787650 TI - The treatment of ammonia poisoning by taurine in combination with a broncholytic drug. PMID- 11787651 TI - Post-transcriptional regulation of cysteine dioxygenase in rat liver. AB - Changes in hepatic cysteine dioxygenase (CDO) activity in response to diet play a dominant role in regulation of cysteine catabolism and taurine synthesis. We have conducted several studies of the molecular regulation of CDO activity in rat liver and rat hepatocytes. Compared to levels observed in liver of rats fed a basal 10% casein diet, up to 180-fold higher levels of CDO activity and protein were observed in liver of rats fed diets that contained additional protein, complete amino acid mixture, methionine, or cystine. Neither CDO activity nor CDO protein was induced by excess non-sulfur amino acids alone. Excess sulfur amino acids or protein did not significantly increase the concentration of hepatic CDO mRNA. Preliminary studies indicate that the polysome profile for association of CDO mRNA with polysomes is not altered by an increase in dietary protein level, suggesting that regulation may be posttranslational and possibly involve a decrease in the rate of CDO degradation. In primary cultures of rat hepatocytes, CDO mRNA, protein, and activity all virtually disappeared by 12 to 24 h of culture in standard medium whereas CDO protein, but not CDO mRNA, accumulated markedly between 12 and 24 h in hepatocytes cultured in medium with excess methionine or cyst(e)ine. These observations are also consistent with a limited role of transcriptional or translational regulation of CDO in response to diet. PMID- 11787652 TI - The mitochondrial permeability transition and taurine. AB - Perturbed cellular calcium homeostasis has been implicated in both apoptosis and necrosis, but the role of altered mitochondrial calcium handling in the cell death process is unclear. Recently we found that taurine, a naturally occurring amino acid potentiates Ca2+ sequestration by rat liver mitochondria. These data, which accounted for the taurine antagonism on Ca2+ release induced by the neurotoxins 1-methyl-4-phenylpyridinium plus 6-hydroxy dopamine previously reported, prompted us to investigate the effects of taurine on the permeability transition (PT) induced experimentally by high Ca2+ plus phosphate concentrations. The parameters used to measure the PT were, mitochondrial swelling, cytochrome c release and membrane potential changes. The results showed that, whereas taurine failed to reverse changes of these parameters, cyclosporin A completely reversed them. Even though these results exclude a role in PT regulation under such gross insult conditions, they cannot exclude an important role for taurine in controlling pore-opening under milder more physiological PT inducing conditions. PMID- 11787653 TI - Cloning and characterization of the promoter region of the rat taurine transporter (TauT) gene. PMID- 11787654 TI - Tests of forced expiration and inspiration. AB - Analysis of the volume versus time curve during a maximum effort forced expiratory vital capacity maneuver started from total lung capacity (TLC) is by far the most performed test of respiratory mechanics, having spread from the laboratory to the wards and outpatient clinics and gradually into the offices of general practitioners. In particular, forced expiratory volume in 1 second (FEV1) is the best characterized test of respiratorv function; information on changes with age, gender, ethnic group, growth and disease is more developed than for any other test, repeatability is good, and it provides useful information across the whole range from normal to advanced disease. PMID- 11787656 TI - Single-breath carbon monoxide diffusing capacity. AB - Measurement of DL(CO) remains a clinically useful way to assess transfer of gases across the lung. It is important, however, to be vigilant in controlling the sources of variation and to be aware of those that remain when interpreting the measured values. PMID- 11787655 TI - Lung volumes and elasticity. AB - The respiratory system is an elastic structure changing volume when pressures are generated by inspiratory or expiratory muscles. If the muscles are relaxed the respiratory system returns to its relaxation volume (Vr) (referred to in the pediatric literature as the elastic equilibrium volume [EEV]), which in normal subjects is the end-expired volume or functional residual capacity, FRC, where alveolar pressure is equal to atmospheric pressure. PMID- 11787657 TI - Bronchoprovocation testing. AB - Bronchoprovocation testing has been performed for more than 50 years. Challenge testing with nonselective agents has been used widely for the assessment of airflow limitation in patients, and has been used in the research setting to better characterize the pathophysiology of bronchial responsiveness. Based on this large body of literature, detailed guidelines are now available to allow for standardization of testing methodology. Such standardization is critical to achieve safe, accurate, and reproducible test results that may be interpreted meaningfully. Currently, bronchoprovocation testing with direct-acting stimuli such as methacholine is used most frequently in the clinical arena, but, in recent years, considerable interest has been developing in the use of indirect stimuli. (57) It now is recognized that bronchial hyperresponsiveness to indirect stimuli (e.g., exercise, cold air, and AMP) is highly specific for asthma and may have greater clinical relevance than does responsiveness to direct stimuli. (8) As a result, testing with indirect agents may become employed more widely in the future. PMID- 11787659 TI - Clinical exercise testing. AB - Clinical exercise testing is increasingly being utilized in clinical practice because of the valuable, often unique information that it provides in patient diagnosis and management. This is also due to a growing awareness that resting cardiopulmonary measurements provide an unreliable estimate of functional capacity. A continuum of exercise testing modalities for functional evaluation from "low tech" to "high tech" will be discussed. These include the six minute walk test, shuttle walk test, exercise induced bronchoconstriction test, cardiac stress test, and cardiopulmonary exercise testing. The main focus of this article will be cardiopulmonary exercise testing including indications, important measurements, salient methodological considerations, and interpretation. PMID- 11787658 TI - Respiratory muscle testing. AB - Respiratory muscles are a vital component of the respiratory system. Compromise in the function of respiratory muscles is assessed with a careful history, determination of the breathing frequency, and observation of the pattern of thoracoabdominal movements in the upright and supine positions. The most important diagnostic tools include measurement of lung volumes, FVC, oximetry, Pi(max) and Pe(max), and SNIP. Measurement of Pes and Pga pressures, Tw Pmo, phrenic nerve stimulation, magnetic stimulation, and EMG add new dimensions to the study of these muscles. These tools are helpful in understanding patients with acute and chronic disease that affects the respiratory muscles. PMID- 11787660 TI - Pulmonary function tests in preoperative pulmonary evaluation. AB - Pulmonary function testing (PFT) is used extensively by pulmonary specialists to address two common clinical questions: (1) What is the risk of a postoperative pulmonary complication in an individual with lung disease? and (2) Will the patient be able to tolerate lung resection surgery? Today, there are numerous tests available to measure pulmonary function; making judicious use of these tests essential. In this article, the authors describe significant postoperative pulmonary complications, and discuss the surgical and patient factors contributing to the risk of these complications. They provide an evidence-based approach using pulmonary function data to determine an individual patient's risk for pulmonary complications associated with three types of surgical procedures upper abdominal, cardiac, and lung resection-and discuss recommendations for risk education. PMID- 11787661 TI - Pulmonary function tests in interstitial lung disease: what role do they have? AB - Pulmonary function tests have been widely accepted and utilized in the management of interstitial lung diseases. Although the tests performed have changed little over the past several decades, extensive literature has been published highlighting their clinical role in the diagnosis, staging, prognostication, and follow-up of patients with a wide variety of interstitial lung diseases. PMID- 11787662 TI - Pulmonary function test abnormalities in pulmonary vascular disease and chronic heart failure. AB - Diagnostic criteria based on pulmonary function testing for pulmonary vascular disease and CHF are imprecise. Although these tests constitute a necessary part of the work-up of a patient with dyspnea, additional studies are required to obtain a final diagnosis in the setting of cardiopulmonary vascular disease. In contrast, specific pulmonary function tests may offer an objective means of assessing severity of dysfunction resulting from pulmonary hypertension or CHE Serial measurements of pulmonary function offer insight into general and specific patterns of cardiopulmonary vascular disease and are useful in evaluating response to treatment. PMID- 11787663 TI - Pulmonary function testing in obesity, pregnancy, and extremes of body habitus. AB - Knowing the effect body habitus can have on pulmonary function is important when there is a concern of an underlying respiratory impairment. The pattern of PFT abnormaLities can help distinguish an underlying ventilatory defect as deriving from the body habitus or from a second process. There are limitations, however. Individuals who are obese and have the same weight will likely have different degrees of impairment, for instance. It then becomes difficult to predict the effect body habitus will have in each patient. It therefore is vitally important to evaluate these patients using other clinical data to decide whether the ventilatory defect can be explained by body habitus alone. It also should be noted that some of the more subtle physiologic changes that occur in these conditions are still not fully understood. Hopefully, further insight into these changes can be obtained with further investigation. Certainly, better predictors of the impact of the patient's weight, abdominal girth, and other anthropomorphic data on PFT results would be extremely helpful in the evaluation of these individuals. PMID- 11787664 TI - Pulmonary function testing in neuromuscular disease. AB - Pulmonary function testing is useful in the diagnosis and management of patients with neuromuscular disease. It is important, however, to keep in mind that certain tests commonly used to assess these patients, such as MIPs and MEPs, although useful, are fraught with potential error and rigorous attention should be paid to technical details when performing them. In addition, many studies have shown that pulmonary impairment does not always parallel generalized muscle impairment and thorough testing therefore should be done in any patient with neuromuscular disease to assess the level of respiratory compromise accurately. In addition, the clinician should be aware that the pattern of involvement-bulbar versus inspiratory, versus expiratory muscle weakness-may vary markedly among patients, even with the same diagnosis, so testing should be tailored to detect these patterns. Furthermore, serial follow-up examinations should be performed to track the rate of deterioration so that therapeutic interventions can be initiated before respiratory crises occur. PMID- 11787665 TI - Pulmonary function tests at work. AB - Occupational exposures remain an important cause of lung disease. A number of PFTs are used in the occupational setting, including spirometry, PEF recordings, methacholine challenge testing, lung volume, and DL(CO). These tests are used in a number of situations, including the clinical evaluation and management of patients with possible occupational lung disorders, preplacement and fitness-for duty examinations, medical screening of exposed workers, impairment and disability evaluations, and research. The diagnosis of occupational lung disease has serious consequences for a worker and, in addition to a careful occupational history, usually requires objective assessment using PFTs. Serial PFTs are useful in following such patients and screening exposed populations of workers for respiratory conditions. PMID- 11787666 TI - The use of pulmonary function testing in piloting, air travel, mountain climbing, and diving. AB - Millions of people engage in occupational or leisure activities at high altitude or at variable depths below sea level. This article presents an overview of the utility of pulmonary function testing in evaluating complications and other consequences of exposure to high and low pressure environments. The authors review recent literature concerning expected changes in pulmonary function with hyperbaric and hypobaric exposures. The article provides guidance for clinicians evaluating mountain climbers, pilots, aircrew members, airline passengers and deep sea divers. PMID- 11787667 TI - Exhaled monoxides as a pulmonary function test: use of exhaled nitric oxide and carbon monoxide. AB - Although there has been tremendous improvement in the technologic ability to measure exhaled gases and monitor biologic processes in the lung, it has not yet found a clinical role outside the research laboratory. Common themes seem to be significant overlap in the amount of exhaled gases in clinically distinct populations, confounding variables such as infection, smoking, and environmental exposure, and lack of consistent change with disease management. If these tests are ever to be used by the general pulmonologist, consistent links between the measurements and the response to disease modification will need to be demonstrated at the very least and, ideally, the clinician would like to see improved outcomes when these noninvasive tests are employed regularly. PMID- 11787668 TI - Examples of pulmonary function in different conditions. AB - This article presents examples of pulmonary function in different conditions. The emphasis is on the routine tests, but examples of respiratory muscle assessment, simple exercise testing, and flow-volume curves are included. PMID- 11787669 TI - Simple office spirometry. AB - Spirometric measurements are as fundamental to medicine as are measurements of pulse, blood pressure, temperature, height, and weight. Spirometric measurements should be considered important vital signs. Any deviations from "normal" measurements can point primary care physicians toward the use of behavioral modification or effective pharmacologic agents to prevent or forestall their patients' premature morbidity and mortality from many disease states, including premature deaths from all causes. PMID- 11787670 TI - A low-fat diet but not food restriction improves lactational performance in obese rats. AB - Rats fed a high-fat diet before and during lactation have difficulty initiating lactation and have high pup mortality rates, low milk production and, consequently, poor pup growth. To determine if these adverse outcomes can be mitigated with dietary changes made after delivery, obese Sprague-Dawley rats (who had previously been fed a high-fat diet [AIN-93M, modified to contain 35% fat, w/w]) were assigned at parturition to continue to be fed this diet (HF) or switched to free access to a corresponding low-fat (LF) diet (AIN-93M, 4% fat w/w) or switched to the LF diet and restricted to consuming only 75% of ad libitum intake (LF/R). Dams lost weight during lactation, but weight loss was much less in the LF group (19g) than in the other two groups (47 and 59g, HF and LF/R, respectively). There was no appreciable change in body water; body fat decreased by about half in all groups, but most substantially in the LF/R group. Compared with the HF group, milk production was 50% higher in the LF group and 12% lower in the LF/R group. Milk lipid concentration tended to be higher and milk water concentration lower in the HF compared with the other two groups. Growth of the litters of the LF dams was significantly higher than both HF and LF/R dams. These results indicate that switching to a low-fat diet mitigates the negative effects of obesity and continued high-fat feeding on lactational performance and pup growth. Consumption of restricted quantities of a low-fat diet negatively affected milk production and failed to improve pup growth, despite the dams' mobilization of body fat in support of lactation. PMID- 11787671 TI - Human lactoferrin in the milk of transgenic mice increases intestinal growth in ten-day-old suckling neonates. AB - Regulatory roles and a signaling receptor have been proposed for the milk protein lactoferrin (Lf), but none has been definitively characterized. Nichols and colleagues (1987) observed that human lactoferrin (hLf) stimulated thymidine incorporation into the DNA of rat intestinal crypt cells. We tested the hypothesis that chronic Lf administration stimulates intestinal growth by studying neonatal mice suckling transgenic dams secreting about 12 mg/mL hLf in their milk. Specifically, nontransgenic litters were adjusted to eight pups each and cross-fostered to transgenic dams. Controls were pups suckling nontransgenic dams of the same strain. On day 10 postpartum pups were weighed, sacrificed, and the small intestines were weighed, measured, and stored for later determination of enzyme activities. The results indicate that intestinal growth was increased in neonates suckling transgenic dams. The weight of the small intestine was increased about 27% when the pups received milk containing hLf. Intestinal length only increased about 6.5% suggesting that Lf in milk enhanced mucosal growth. The ratio of maltase to lactase in the duodenal segment of the small intestine, an indicator of maturation, was also significantly increased in the pups suckling transgenic milks. Our results imply that chronic oral consumption of human Lf promotes the growth and maturation of the intestinal mucosa, and suggest a possible therapeutic role for the agent in premature infants as well as in patients with bowel damage. PMID- 11787672 TI - Human milk and the response of intestinal epithelium to infection. PMID- 11787673 TI - Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. AB - The whey protein alpha-lactalbumin, derived from human milk, has been shown to inhibit proliferation of mammary epithelial cells and rat kidney cells. We have shown that bovine alpha-lactalbumin also has antiproliferative effects in human colon adenocarcinoma cell lines. During a 5-day dose-dependent growth study, bovine alpha-lactalbumin was added to Caco-2 or HT-29 monolayers in amounts from 5 to 35 microg/mL. Low concentrations of alpha-lactalbumin (10-25 microg/mL) stimulated growth during the first 3 to 4 days. After growing for 4 days, proliferation ceased and viable cell numbers decreased dramatically in the alpha lactalbumin-treated cultures, suggesting a delayed initiation of apoptosis. This experiment demonstrates the acute bioactive effects of small concentrations of alpha-lactalbumin, compared with the high concentrations of other proteins in the media. These results suggest that alpha-lactalbumin in milk may promote health by inhibiting growth of potential cancer cells. Further studies will identify the role of calcium in the bioactivity of alpha-lactalbumin. PMID- 11787674 TI - Assembly and secretion of the lipid globules of milk. PMID- 11787675 TI - Prolonged breast-feeding (six months or more) and milk fat content at six months are associated with higher developmental scores at one year of age within a breast-fed population. AB - Since dietary fats may affect brain composition and function in early life, we evaluated developmental indices at 1 year of age in relation to the duration of breast-feeding and the milk fat composition in a breast-fed population. A blinded monitor administered the Bayley test (2nd edition) to 1-year-old subjects born at term and exclusively breast-fed for at least 3 months. Weaning foods were introduced from the 5th month onward. Mothers' milk lipid composition (fat [wt/dL], fatty acid [wt/dL], FA% [% of total fatty acids]) was determined at 0, 1, 3, 6, 9, and 12 months. Statistics used were Student's t-test, Pearson's r, and multiple regression. Forty-four infants out of 95 recruited at birth met inclusion criteria. There was a progressive reduction of the number of breast-fed babies to 29 (6 mo), 17 (9 mo), and 10 (12 mo). Breast-feeding for 6 months or longer gave a 6.6-point advantage (95% confidence interval, -0.6, 13.8; P = 0.07 for the Bayley psychomotor developmental index (PDI) and 2.0 for the Bayley mental developmental index (MDI) (95% confidence interval, -3.2, 7.3; NS) compared with the 15 subjects breast-fed for fewer than 6 months. Among the milk lipid factors, the fat weight (mg/dL) at 6 months showed the highest association with the MDI (r = 0.55, P = 0.002). Thus, prolonged breast-feeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats contributing energy and/or affecting brain composition. PMID- 11787676 TI - Presence of carotenoid, an anticarcinogenic marker, in nipple aspirates postlactation. AB - Case-controlled studies have identified a protective effect of lactation against breast cancer; however, little is known about the nature of this protective mechanism. The purpose of this study was to examine postweaned, nipple aspirate fluid (NAF) from women, ages 18 to 45, for carotenoid, a known antioxidant and anticarcinogenic marker, and compare carotenoid availability in NAF with that reported in colostrum. Women who had lactated at least 6 months and weaned for at least 6 months were recruited into the study A prestudy and poststudy serum prolactin level was obtained. NAF was obtained through a nipple aspirator method. Total carotenoid ranged from 0.4 to 4.0 microg/mL, with a mean level of 1.9+/-1.2 (SD). Women who had weaned earlier (<12mo) had significantly more carotenoids than those who had lactated longer (>12mo) (P = 0.04). These levels were similar to those known to occur in colostrum. This research elucidates possible mechanisms of the protective effect of lactation on the microenvironment of the breast. PMID- 11787677 TI - The anticarcinogenic conjugated fatty acid c9, t11-c18:2, or rumenic acid, in human milk: amounts and effects. AB - The conjugated linoleic acid (CLA) c9, t11-C18:2 has been detected in human milk by gas-liquid chromotography (GLC) using standards for tentative identification. The amounts found were: 5.5 mg/g fat, Australia, 1988; and 3.6 mg/g fat, Idaho, 1997. We also employed GLC and standards and confirmed the identity of coeluting peaks by mass spectrometry. Our values were 1.8+/-0.02 mg/g fat. CLA inhibits growth of several cancers, is antiatherosclerotic, partially overcomes catabolic responses to endotoxin injection, enhances weight gain and improves feed efficiency in rats, and modulates immune response and bone deposition. The dietary sources are ruminant-derived foods, particularly aged cheese. PMID- 11787678 TI - Long-chain polyunsaturated fatty acid concentrations in human hindmilk are constant throughout twelve months of lactation. AB - We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk. PMID- 11787679 TI - Parenteral infusion of a lactating woman with intralipid: changes in milk and plasma fatty acids. AB - A nursing woman afflicted with short bowel syndrome received parenteral infusions of Intralipid. In the morning following 2 nights of infusion, samples of milk and blood were taken; additional samples were taken the morning after 1 and 2 nights of no infusion. The fatty acid composition of these samples was determined by gas chromatography. The Intralipid infusion contained 51.5% linoleic acid (C18:2). The C18:2 content of the milk was highest (14%) after each infusion and dropped to about 10% on days 1 and 2. Inverse changes were seen in stearic acid (C18:0). The C18:2 content of the plasma showed little change, remaining at about 23%. These results provide further direct evidence that the composition of milk fatty acids can be influenced by changes in the composition of external sources of fatty acids to the lactating mother. PMID- 11787680 TI - Investigation of long-chain polyunsaturated fatty acid metabolism in lactating women by means of stable isotope techniques. AB - Long-chain polyunsaturated fatty acids are important components of human milk that seem to influence infant development. After oral administration of U-13C labeled linoleic acid to a lactating woman the recovery of tracer in milk linoleic acid was 6.4%, whereas tracer recovery in dihomo-gamma-linolenic acid (DGLA) was 0.3% and in arachidonic acid (AA), <0.01%. Some 14.9% of linoleic acid intake was converted to breath-CO2. In combination with data on dietary intake and quantitative milk output, we estimate that 23% of milk linoleic acid, 7% of milk dihomo-gamma-linolenic acids and 0.5% of milk arachidonic acid were contributed by direct endogenous conversion and transfer from dietary linoleic acid. These findings lead us to conclude that long-chain polyunsaturated fatty acids for human milk synthesis are produced in the body, but either a relatively low percentage is contributed under these dietary conditions, or there are large body pools for intermediate storage of these fatty acids that are utilized for secretion into milk. PMID- 11787681 TI - Structural and functional aspects of three major glycoproteins of the human milk fat globule membrane. AB - The MUC1 mucin, lactadherin, and butyrophilin are 3 major components of the human milk fat globule membrane. The mucin inhibits binding of S-fimbriated Escherichia coli to buccal epithelial cells, and lactadherin prevents symptomatic rotavirus infection in breast-fed infants. Butyrophilin has been suggested to be a structural component of the human milk fat globule (HMFG) membrane and to have receptor functions, but has no known anti-infective activity. These HMFG glycoproteins also are present in skimmed milk, possibly associated with phospholipid micelles, while mucin is also in a soluble form. Mucin and lactadherin resist digestion in the stomach of milk-fed infants, while butyrophilin is rapidly degraded. The MUC1 mucin is an extended rod-like structure forming part of the glycocalyx on the surface of many epithelial cells and membranes of milk, and may act as a decoy for binding of infective agents. The extracellular segment of butyrophilin has homology to Ig superfamily receptors and an intracellular domain with homology to developmentally regulated proteins. Lactadherin is a laterally mobile cell adhesion molecule that interacts with integrins and has a novel means of membrane-association involving specific binding to phosphatidylserine. The structural and functional aspects of these glycoproteins are discussed with regard to their role in human milk for breast fed infants. PMID- 11787682 TI - Anti-infectious properties of the human milk fat globule membrane. AB - Secretory immunoglobulin A (sIgA), the predominant antibody fraction of human milk, represents a major protective factor against neonatal infection. Until now, sIgA had been identified only in the humoral fraction of human milk. For bovine milk an association between sIgA and the milk fat globule (MFG) membranes has been demonstrated. The aim of our study was to assess whether sIgA is associated with the MFG membranes in human milk. Using anti-sIgA-agglutinated human MFG and immune fluorescence microscopy, we demonstrated that sIgA is, in fact, associated with human MFG. Subsequently, by electrophoretic separation of human MFG membranes and Western blotting, we demonstrated specific sIgA bands, suggesting that sIgA is truly an integral part of the human MFG membrane. This may be of physiological relevance, as undigested and functional human MFG are found in the stools of the newborn. PMID- 11787683 TI - Homeostasis of the mucosal immune system: human milk and lactation. AB - External secretions, including milk, contain large amounts of immunoglobulins (Ig) and innate factors of humoral immunity The Ig isotype distribution, their origin, transport, and absorbability from the gut lumen differ greatly among various species. Milk of primates contains mainly secretory IgA (sIgA) which has unique biological properties. The functional advantages of sIgA compared with other Ig isotypes include its resistance to proteolysis, presence of 4 to 8 antigen-binding sites, carbohydrate moiety-mediated antiadherence properties, and inhibition of complement activation. Although IgA exhibits its protective effect mainly on mucosal surfaces, internalization by cells expressing various IgA receptors suggests additional protective functions. PMID- 11787684 TI - Anti-inflammatory characteristics of human milk: how, where, why. AB - When first proposed, the hypothesis that human milk was anti-inflammatory was supported by 2 observations: poor function of milk leukocytes and the presence in milk of components that could modify inflammatory processes. This hypothesis is now supported by studies documenting anti-inflammatory effects in animal models and suppression of humoral and cellular components of inflammation in vitro. To date, two mechanisms have been demonstrated: alteration of leukocyte function and modification of cytokine biology. It is not clear whether these mechanisms are only topical effects in the digestive tract, or whether absorption of milk components results in systemic effects. While inflammation benefits the host as a defense mechanism and precursor to immune responses, it also contributes to the clinical manifestations of illness and is an important early component of wound healing responses that result in scar. The biological effects of milk's anti inflammatory character may be to minimize clinical symptomatology without losing immunoresponsiveness for the breast-fed infant, and to minimize scar formation during healing responses. PMID- 11787685 TI - Development of a topical vaginal microbicide: lessons learned from human milk. AB - Vaccines are not presently available to prevent adherence and transmission of many common pathogens at mucosal surfaces. As a result, sexually transmitted diseases were one of the most commonly reported infections in the US in 1999. New methods are needed to reduce the spread of mucosal infections. Providing nonspecific protective factors, such as lipids and retinoids found in human milk to mucosal surfaces could reduce mucosal infection caused by viruses, e.g., herpes simplex virus-1 (HSV-1) and bacteria, e.g., Pseudomonas aeruginosa. Human milk lipids enzymatically modified to produce monoglycerides were antimicrobial and inactivated enveloped viruses, as well as gram-positive and gram-negative bacteria. Enveloped viruses were inactivated in seconds following contact with antimicrobial lipids, and P. aeruginosa infectivity was reduced by 99.9% after 2 hours. Transmission of pathogens at mucosal surfaces can also be prevented using retinoids that inhibit viral replication. In a human embryonic intestinal cell line the retinoic acid (RA) derivatives all-trans-RA and 9-cis-RA (10 microg/mL) decreased the production of HSV-1 and Echo-6 viruses by 1-2 log10 over a 48-hour period. In addition, all-trans-RA inhibited HSV-1 replication in Vero cells as effectively as interferon beta, reducing viral production by 2.5log10. These studies indicate that lipids and retinoids could be part of a topical microbicide to prevent mucosal infections. PMID- 11787686 TI - Does human lactoferrin in the milk of transgenic mice deliver iron to suckling neonates? AB - Lactoferrin is an iron-binding glycoprotein abundantly present in human milk, and has been postulated both to increase and to decrease intestinal iron absorption. To examine this problem, the interaction of milk iron with pup hemoglobin was studied in controls and in transgenic mice overexpressing human lactoferrin in their milk (2 lines expressing 12 mg/mL and 4 mg/mL, respectively). At day 14 of gestation, pregnant mice were switched from a diet of commercial chow containing iron at 300 mg/kg to diets containing 5, 15, or 50mg iron/kg; controls continued on chow. Nontransgenic pups were cross-fostered to transgenic dams to ensure that any results found in the pups were the effect of milk components. The hemoglobin level in the blood of 10-day-old suckling neonates was measured and calculated as total hemoglobin per pup. The total hemoglobin levels were lower in the pups receiving milk high in human lactoferrin, but the difference reached significance (P < 0.02) only at the highest level of dietary iron. Our findings do not support the hypothesis that lactoferrin functions as an intestinal iron scavenger, at least at high doses. PMID- 11787687 TI - Changes in lactoferrin and lysozyme levels in human milk during the first twelve weeks of lactation. AB - Changes in the lactoferrin and lysozyme concentration of human milk during lactation were determined by microparticle-enhanced nephelometric immunoassays of 360 milk samples collected from 64 lactating volunteers. These 360 samples were colostrum from days 1 to 5 postpartum (142 samples), transitional milk from days 6 to 14 (106 samples), and 112 mature milk samples obtained from days 15 to 28 (34 samples), from days 29 to 56 (50 samples) and from days 57 to 84 postpartum (28 samples). The concentration and percentage of lactoferrin vs. total protein were found to be significantly higher in colostrum (5.8 g/L, 27%) than in transitional milk (3.1 g/L, 22%) or day 15 to 28 mature milk (2.0 g/L, 19%), then increased in day 29 to 56 mature milk (2.2 g/L, 22%) and day 57 to 84 mature milk (3.3 g/L, 30%). The concentration of lysozyme decreased from colostrum (0.37 g/L) to transitional milk (0.27g/L) and day 15 to 28 mature milk (0.24 g/L), then increased in day 29 to 56 mature milk (0.33 g/L) and was highest in day 57 to 84 mature milk (0.89 g/L). The percentage of lysozyme vs. total protein was found to be always rising during lactation: colostrum, 2%; transitional milk, 2%; days 15 to 28, 2%; days 29 to 56, 3%; and days 57 to 84 mature milk, 8%. PMID- 11787688 TI - The association of allergic sensitization in mother and child in breast-fed and formula-fed infants. AB - Human milk contains immunologically active substances potentially capable of altering infant immune response. As part of the prospective Children's Respiratory Study, we assessed whether the association between maternal allergic status and allergic status of the child was altered by breast-feeding. Skin-prick tests for 7 common allergens were administered to 702 6-year-old children and their mothers. The percentage of children sensitized to specific allergens, maternal skin test response to that allergen, and whether or not the child was ever breast-fed was determined. Findings indicated that specific sensitization in the mother was associated with specific sensitization in the child only if the child was breast-fed. This indirectly supports the hypothesis that contents of milk differ with maternal allergic status, and appear to affect allergic status in the child. These results suggest that milk from allergic mothers either promotes a Th2 type immune response or suppresses Th1 immune response in the child. PMID- 11787689 TI - Vesicular transport of soluble substances into mouse milk. AB - Utilizing a novel protocol to study transport of substances into mouse milk in situ, we have shown that many "fluid-phase" markers are taken up by mammary epithelial cells and deposited in milk. Since the tight junctions are closed and impermeable even to small molecules, extra-alveolar substances (those not synthesized by the alveolar cells) must be transported into the milk by the epithelial cells themselves. The markers we have used include dextran, lucifer yellow dye, horseradish peroxidase, and albumin. Using these markers and immunostaining for endogenous proteins, we have visualized transcytotic vesicles involved in transporting these markers to milk. PMID- 11787690 TI - Glycoconjugates in human and transgenic animal milk. AB - Human milk samples contain a particularly rich collection of oligosaccharides compared with other milk samples. The synthesis of these molecules should depend on the expression of glycosyltransferases and the presence of sugar nucleotides in lactating mammary glands. We set out to produce transgenic animals expressing glycosyltransferases during lactation with the purpose of exploring the following issues: a) Is it possible to synthesize human milk oligosaccharides in lactating mammary glands of nonhuman animals?, b) Is it possible to express during lactation homologous, tissue specific glycosyltransferases that are not normally expressed in lactating mammary tissue?, and c) What is the effect of expressing a human glycosyltransferase in different animal species? Simultaneously, we embarked on a research program to study short-chain neutral human milk oligosaccharides--no larger than hexasaccharides--to understand the natural variation of milk sugars and glycoproteins. The reagents and methods developed to study human milk oligosaccharides and glycoproteins were also applied to the study of milk from transgenic animals. Our results indicate that mice predictably express transgene-encoded glycosyltransferases and their secondary gene products, oligosaccharides and remodeled glycoproteins. This was true even when the transgene encoded a homologous galactosyltransferase. Also, it was possible to synthesize fucosylated glycoconjugates in mouse milk using two different fucosyltransferases, thus demonstrating that is feasible to emulate the synthesis occurring in the human lactating mammary gland. Experiments with transgenic rabbits yielded different phenotypes, some of them unexpected. Taken together, our results answer the questions stated above but open even more intriguing areas of inquiry. PMID- 11787691 TI - Mass spectrometric investigations of human milk oligosaccharides. AB - Human milk oligosaccharides (OS) have been fractionated by gel permeation chromatography (GPC) and analyzed by mass spectrometry (MS). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/MS) and electrospray ionization (ESI) ion trap/MS were used. Using a large human milk pool, the MALDI TOF/MS analysis of high-molecular-mass GPC fractions showed that complex, multiply fucosylated and/or sialylated OS are present over a larger mass range than described previously Acidic oligosaccharides could be detected from low retention-time GPC fractions with masses up to 4000 Da, which has not been reported before. PMID- 11787692 TI - Human milk oligosaccharides: a novel method provides insight into human genetics. AB - Human milk is a unique reservoir of oligosaccharides. The presence of many of these oligosaccharides is determined genetically and is related to the Lewis blood group and secretor antigen status of each donor. A method to quantitate neutral human milk oligosaccharides was developed. Sample preparation was based on a single centrifugation-filtration step that yields oligosaccharide extracts. These extracts first were fractionated to remove a significant portion of their lactose content and were analyzed using high-pH anion-exchange chromatography. Oligosaccharide profiles from 386 milk samples obtained in this fashion generated quantitative information on lactose, the neutral cores lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNneoT), and the key fucosylated oligosaccharides. Additionally, the profiles provided genetic footprints of the Lewis and secretor status of the donors. Furthermore, unusual profiles that could not have been predicted from known genotypes were found. For this reason, milk glycoproteins were studied using carbohydrate-binding probes. Results confirm that oligosaccharides are an accurate predictor of the Lewis blood group status of the donor, and that glycosyltransferases have exquisite specificities. The data obtained in this study corroborate that Lewis-related antigens are tissue specific. This attribute of immunodominant carbohydrate sequences has significant implications for epidemiological studies of breast-fed infants. PMID- 11787693 TI - Detection of four human milk groups with respect to Lewis-blood-group-dependent oligosaccharides by serologic and chromatographic analysis. AB - Oligosaccharides from human milk samples obtained from individual donors were analyzed using high-pH anion-exchange chromatography. Three patterns of neutral oligosaccharides were detected corresponding to milk groups already described. These oligosaccharide groups correspond to the Lewis blood types Le(a-b+), Le(a+b ), and Le(a-b-). A new carbohydrate pattern was detected in a milk sample from a Le(a-b-) person in which only nonfucosylated oligosaccharides and compounds bearing alpha1,3-linked fucosyl residues were found. This finding led to the hypothesis that there exist 4 different oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood group system. PMID- 11787694 TI - Bioactive components of human milk: evolution, efficiency, and protection. PMID- 11787695 TI - Characterization of oligosaccharides in milk and feces of breast-fed infants by high-performance anion-exchange chromatography. AB - Human milk contains a large amount of oligosaccharides, which represent its third largest solute. Nevertheless, both the metabolism and the role of these substances are still largely unknown. A previous study we conducted documented that the amount of oligosaccharides excreted in the feces varies from 6% to 13% of the 24-hour ingested oligosaccharides. The aim of this study was to characterize the pattern of oligosaccharides in the feces compared with the pattern of the ingested milk. Six term newborn infants were studied at the end of the first month of life. A 7:00 AM milk sample was obtained with an electric breast pump. Feces were collected during the day of milk sampling. Analyses of oligosaccharides were performed using high-pH anion-exchange chromatography with pulsed amperometer detection. Pure milk oligosaccharides were used as reference standards. The chromatographic profile of the oligosaccharides present in the feces and in the milk samples showed more than 40 peaks, 20 of which have been identified. The oligosaccharide profile observed in the feces was similar to the pattern of oligosaccharides present in the milk ingested. A significant difference was represented by the almost complete absence of lactose in the feces of all infants and of sialyllacto-N-tetraose a and disialyllacto-N-neotetraose in 3 samples. A substantial reduction of lacto-N-tetraose was observed in 5 samples. Our results demonstrate that the oligosaccharide profile in the feces is similar to that of the ingested milk. Approximately 40% to 50% of the total ingested oligosaccharides can be found in feces of breast-fed infants. PMID- 11787696 TI - Introduction to the Macy-Gyorgy award lecture. PMID- 11787697 TI - Survival of human milk oligosaccharides in the intestine of infants. AB - Several human milk oligosaccharides inhibit human pathogens in vitro and in animal models. In an infant, the ability of these oligosaccharides to offer protection from enteric pathogens would require that they withstand structural modification as they pass through the alimentary canal or are absorbed and excreted in urine. We investigated the fate of human milk oligosaccharides during transit through the alimentary canal by determining the degree to which breast fed infants' urine and fecal oligosaccharides resembled those of their mothers' milk. Oligosaccharide profiles of milk from 16 breast-feeding mothers were compared with profiles of stool and urine from their infants. Results were compared with endogenous oligosaccharide profiles obtained from the urine and feces of age-, parity-, and gender-matched formula-fed infants. In all cases, oligosaccharides were extracted, purified, reduced, and separated into acidic and neutral species; the latter were perbenzoylated and subjected to reversed-phase high-performance liquid chromatography. Structures were determined by mass spectrometry after debenzoylation. Among breast-fed infants, concentrations of oligosaccharides were higher in feces than in mothers' milk, and much higher in feces than in urine. Urinary and fecal oligosaccharides from breast-fed infants resembled those in their mothers' milk. Those from formula-fed infants did not resemble human milk oligosaccharides, were found at much lower concentrations, and probably resulted from remodeling of intestinal glycoconjugates or from intestinal bacteria. Most of the human milk oligosaccharides survived transit through the gut, and some were absorbed and then excreted into the urine intact, implying that inhibition of intestinal and urinary pathogens by human milk oligosaccharides is quite likely in breast-fed infants. PMID- 11787698 TI - Comparison of oligosaccharides in milk specimens from humans and twelve other species. AB - Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. Ambiguous structures were determined by mass spectrometry. All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. PMID- 11787699 TI - Human milk lipids bind Shiga toxin. AB - Hemolytic uremic syndrome, a serious complication of Shiga toxin-associated diarrhea, is rare before 6 months of age. Immunologic and nonimmunologic factors present in human milk may partially explain this observation. In prior studies, we have demonstrated that human milk contains Gb3, the receptor for the B subunit of Shiga toxin, and also contains secretory IgA (sIgA) against the toxin. We therefore sought to determine the relative importance of milk glycolipid and toxin-specific sIgA in toxin binding. We studied two populations that differed in their frequency of exposure to Shiga toxin. Human milk samples obtained from healthy donors from Boston and Buenos Aires were separated by centrifugation into aqueous (antibody enriched) and cream (glycosphingolipid enriched) fractions. An emulsion of equal volumes of aqueous phase or cream layer of each sample and purified Shiga toxin was incubated, and the amount of free toxin present in each was determined by enzyme immunoassay. The cream layers bound 85%+/-2 (mean +/- SE) (Argentina milk samples) and 86%+/-1 (Boston milk samples) of Shiga toxin. In contrast, the soluble fraction in samples from Buenos Aires, a population expected to frequently have antibodies to Shiga toxin, bound more toxin (48%+/-2) than did this fraction in samples from Boston, an area where toxin exposure is infrequent (30%+/-3) (P < 0.0001). Toxin-binding lipids present in human milk are biologically active and may contribute to the putative protective effect of human milk. In a population frequently exposed to Shiga toxins (Argentina), protection may be due to both immune (sIgA), and nonimmune (lipid) factors present in human milk. In a population infrequently exposed to Shiga toxins, cream fraction associated glycolipids represent the major toxin binding activity in human milk. PMID- 11787700 TI - Human milk antibacterial factors: the effect of temperature on defense systems. AB - Bovine milk will eventually spoil at refrigeration temperatures, but endogenous or exogenous pathogenic or spoilage bacteria in human milk stored for delayed feeding will die. We investigated the mechanism for these antibacterial properties and their response to high-tempertature, short-time (HTST, 72 degrees C-75 degrees C, 15 sec) and low-temperature long-time (LTLT, 65 degrees C, 30 min) pasteurization. Nonpathogenic Listeria innocua (10(6) cfu/mL) was inoculated into raw and processed bovine and human milk; bacterial plate counts twice weekly determined antibacterial activities. Up to 99% of L. innocua were killed and further growth was inhibited in raw and pasteurized human milk for at least 60 days at 4 degrees C. Reactive IgA antibodies against Listeria antigens were demonstrated by enzyme immunoassay in some human milk samples; sIgA activity against Escherichia coli O antigens was significantly decreased by heat treatments (raw, 1.8; HTST, 1.1; LTLT, 1.3 activity units). Adding human lactoferrin (0.5-20 mg/mL) to the Listeria inoculum (approximately 10(7) cfu/mL) in 1% peptone water did not inhibit bacterial growth. PMID- 11787701 TI - MUC1 and MUC-X, epithelial mucins of breast and milk. AB - While reasons for gross variations in milk composition of the various mammalian species are well established, we will be revealing minor, subtle, yet highly important differences for years to come. One of the distinctive differences of human milk concerns its mucins, MUC1 and MUC-X. These are high molecular mass glycoproteins that occur on the apical surface of the lactating cell and are transferred to the milk fat globule upon its secretion from the cell. Among mammals, it seems that the human has developed the largest, most extended versions of these mucin molecules. Evidence is accumulating that this greater size benefits the human in terms of protection against infections and injurious environmental agents. PMID- 11787702 TI - Overview: conditionally essential nutrients: long-chain polyunsaturated fatty acids. PMID- 11787703 TI - Overview: conditionally essential nutrients: can long-chain polyunsaturated fatty acids and nucleotides qualify? PMID- 11787704 TI - Biotherapeutic agents and disease in infants. AB - Human milk contains many factors that act synergistically or with redundancy in protecting suckling infants from infectious diseases. The rigorous application of the scientific method has shown significant beneficial effects of these specific factors. The beneficial effects of biotherapeutic agents, including prebiotics and probiotics, on the alteration of intestinal microflora and modulation of the local and systemic immune response of infants have been shown. The beneficial effects of these compounds on preventing diarrhea and possibly other infectious diseases in infants serves as a model for the development and use of biotherapeutic agents to treat and prevent infectious diseases in persons of all ages. PMID- 11787705 TI - Long-chain polyunsaturated fatty acids in breast milk: are they essential? AB - The need for long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA, C22:6n3) and arachidonic acid (AA, C20:4n6), in the diet of infants in order to achieve full developmental potential is a matter of intense investigation by several research groups worldwide. It has been widely reported that breast-fed infants perform better on tests that assess neurodevelopmental outcomes than do formula-fed infants. Although human milk contains LC-PUFA that are absent from formula, it is necessary to demonstrate that any beneficial effects of human milk on infant development are purely attributed to the presence of LC-PUFA in human milk and their absence from formula to establish causality. The hypothesis that dietary DHA is associated with developmental outcome needs to be plausible; the effect must be consistent, specific, and independent of confounding factors. The hypothesis is certainly plausible. DHA is avidly incorporated and retained in brain cerebral phospholipids, and a most consistent finding has been the lower level of cerebral DHA in the brains of formula-fed infants (receiving no DHA) relative to those fed human milk (receiving DHA). The formula-fed infants in these studies were generally fed formulas with adequate alpha-linolenic acid levels, and this may indicate a nutritional requirement for preformed DHA. Several studies have compared the effects of breast- and formula-feeding on functional outcomes in preterm and term infants. While many of the outcomes have involved visual testing, others have attempted more global assessments. The results have shown differences in favor of breast-feeding but have been colored by the strong socioeconomic differences between mothers who choose to breast feed and those who choose formula-feeding. Randomized clinical trials involving preterm infants have shown a clear requirement for DHA for full visual and neural development. These results are consistent with primate studies. However, intervention studies with term infants that have attempted to improve the DHA supply of infant formula and hence infant development have not yielded consistent results. Some randomized studies have demonstrated improved visual and developmental indices in supplemented over unsupplemented infants, others have failed to demonstrate an effect. This disparity could be due to methodological and environmental differences. It is also notable that supplemental regimens have not specifically added DHA and have included other LC-PUFA, raising the question as to the specificity of the effect. However, only tissue DHA levels have consistently correlated with outcomes. PMID- 11787706 TI - Specific IgA to lactic acid bacteria in feces of children consuming milk fermented by yoghurt symbiosis and Lactobacillus casei (Danone strain DN 114 001). AB - An immunoreactive role of lactic acid bacteria established in animals has seldom been investigated in humans. In a large-scale clinical study, children from day care centers received either yoghurt (Y), milk fermented by yoghurt symbiosis and Lactobacillus casei (DN 114 001) (YC), or gelified milk (GM) as diet supplements during two 30-day supplementation periods separated by one 30-day period without supplementation. Feces samples were collected before, during, and after the 2nd supplementation period. Proteins were extracted in a buffer containing enzymatic inhibitors. IgA levels were assessed and adjusted to the weight of feces samples. Specific IgA to lactic acid bacteria strains (Streptococcus thermophilus 8901A, 8902A; Lactobacillus bulgaricus; Lactobacillus casei) present in Y and YC were assayed in ELISA and adjusted to individual IgA levels. Mean levels of fecal IgA were within reported ranges for pediatric populations of similar age. IgA levels decreased significantly but transiently in children receiving Y, and increased significantly in children receiving GM, but did not vary in the group of children who were given YC. Specific IgA to the 4 strains tested increased significantly during the supplementation period only in the group of children receiving GM, while it was transient and not significant in children receiving YC. No variation was noted in children given Y Specific IgA to lactic acid bacteria can be assayed in feces. Supplementation with fermented milks might induce a mucosal tolerance to environmental flora. PMID- 11787707 TI - Are breast-fed infants vitamin K deficient? AB - Hemorrhagic disease of the newborn is a disease of breast-fed infants. We have followed 119 exclusively breast-fed infants for up to 6 months of age, who received 1 mg of vitamin K, intramuscularly at birth. As vitamin K is undetectable in cord blood, the only other source in breast-fed infants is human milk. We found persistently low vitamin K1 plasma concentrations in these infants by 4 weeks, and vitamin K concentrations at 2, 4, 6, 8, 12, and 26 weeks averaged 1.18+/-0.99, 0.50+/-0.70, 0.16 +/-0.07, 0.20+/-0.20, 0.25+/-0.34, and 0.24+/-0.23 ng/mL, respectively (lower limit of adult normal = 0.5ng/mL). Vitamin K, in breast milk at 2, 6, 12, and 26 weeks was also very low, averaging 1.17+/-0.70, 0.95+/-0.50, 1.15+/-0.62, and 0.87+/-0.50 mg/mL, respectively. This may be secondary to low maternal vitamin K1 intakes or inability of vitamin K1 to penetrate human milk. We had previously reported a relatively high mean vitamin K intake of 316+/-548 microg in 20 lactating women during the first 6 months of lactation (mean of 60, 3-day dietary recalls) which greatly exceeded the recommended daily allowance of 1 microg/kg/day. The vitamin K content of foods was recently revised downward utilizing newer analytical methods (Booth et al. 1995). Recalculating maternal vitamin K intakes in this original cohort resulted in a dramatic decrease in intake to 74+/-57 microg/day, an amount closely approximating 1 microg/kg/day. We have completed 69 new dietary recalls in 23 lactating women and, combining these data with the previous study, determined a maternal vitamin K1 mean intake of 65+/-48 microg/day (0.8-1.3 microg/kg/day). Other than plasma vitamin K1 concentrations, PIVKA (undercarboxylated prothrombin produced in the absence of vitamin K) is a marker of vitamin K deficiency. We measured PIVKA in 156 cord bloods of full-term infants. Seventy-five (48%) had a significantly elevated PIVKA (> or =0.1 absorption units per milliliter). Seventy seven of these infants who were exclusively breast-fed subsequently had no detectable PIVKA at 4 weeks, but by 8 weeks, 3 were again positive for PIVKA (prothrombin times were normal). Breast-fed infants may benefit from increased maternal vitamin K intakes (>1 microg/kg/day) during pregnancy and lactation. A supplement of 5 mg of vitamin K to lactating mothers will increase the concentration in human milk to 80.0+/-37.7 ng/mL and significantly increase infant plasma vitamin K (Greer et al. 1997). PMID- 11787708 TI - Long-chain polyunsaturated fatty acids (LC-PUFA) during early development: contribution of milk LC-PUFA to accretion rates varies among organs. AB - Long-chain polyunsaturated fatty acids (LC-PUFA) accretion (essential for growth and neural development) was studied from late fetal throughout weaning age in the ferret, a species with maternal LC-PUFA sufficiency during pregnancy and lactation. The data show that a) accretion rate of LC-PUFA is rapid during early postnatal development, b) milk LC-PUFA decrease during lactation, c) adipose tissue LC-PUFA level is directly related to milk LC-PUFA level, while accretion in brain and liver exceeds dietary intake, d) accretion of arachidonic acid occurs earlier than docosahexaenoic acid, suggesting earlier development of n6 fatty acid endogenous synthesis. PMID- 11787709 TI - Gastric proteolysis in preterm infants fed mother's milk or formula. AB - Gastric proteolysis is assumed to be low in the newborn (Britton & Koldovsky 1989). Postprandial pepsin output is significantly lower in preterm infants than adults, 589 vs. 3352U/kg, respectively (Armand et al. 1995, 1996). We now report on gastric proteolysis in preterm infants (gestation age, 29 weeks; postnatal age, 5-6 weeks) gavage-fed mother's milk or preemie formula. The data show that a) the nonprotein component is higher in human milk than formula, b) net proteolysis amounts to 15% of protein, c) gastric proteolysis is lower than lipolysis and, contrary to the latter, is not enhanced by milk feeding (Armand et al. 1996). We suggest that stomach pH, enzyme output, and food structure are the reasons for differences in gastric digestion of protein and fat in infants. PMID- 11787710 TI - Macronutrients in milk from mothers delivering preterm. AB - Premature infants require large amounts of protein and energy to achieve normal growth. Feeding with human milk alone is therefore only regarded acceptable if the protein and energy content is adequate. METHODS: 476 milk samples from 101 mothers delivering before the 32nd gestational week (mean gestational age, 28 weeks) were obtained on a weekly basis until 36 weeks of gestational age and analyzed for true protein, total carbohydrate, and fat content by infrared analysis. Fat measurements were validated with the Folch method. Milk was collected by complete expression with an electric pump into 24-hour pools. RESULTS: The protein concentration decreased significantly with time (P = 0.00001). The carbohydrate, fat, and energy concentration was significantly lower in the first 2 weeks after delivery, after which they increased to a constant level. The macronutrient level in milk was not associated with gestational age (P = 0.3). The energy content of these milk samples was high, and feeding 200 mL/kg would provide sufficient energy until 36 weeks of gestational age for all infants, and 65% of the infants would receive > or =3g total protein/kg/day. PMID- 11787711 TI - Amino acid intake during lactation and amino acids of plasma and human milk. AB - The aim of this study was to determine the free amino acid pool in plasma and milk in marginally nourished lactating women. Twenty-eight rural women (age, 23.9+/-5y; weight 50.2+/-4.9 kg; height, 148.2+/-4.8 cm) were studied under metabolic balance conditions. Subjects were divided into 6 groups (5-6 women in each), representing rural mothers postweaning and in the 15, 3rd, and 6th months of lactation; nonpregnant, nonlactating controls were from rural and urban areas. Amino acid analyses of diet and of plasma and milk samples were performed using a Beckman 6300 amino acid analyzer. Lysine intakes were lower than the recommended intake for lactating women (RDA). Plasma amino acid profiles differed between the lactating and weaned groups: aspartate and isoleucine increased at the 6th month (P < 0.05), while valine declined over weaning time (P < 0.05). In milk, valine and proline decreased at the 6th month (P < 0.05), while serine rose at the 3rd month. Free amino acid pools were 1- to 15-fold higher in plasma than in milk for branched-chain amino acids and basic, aromatic, and neutral amino acids. In mammary tissue these amino acids can be channeled to tissue and milk protein synthesis or to catabolic pathways. Glutamate was 40-fold higher in milk with respect to plasma content. This was the predominant amino acid in the free amino acid pool in milk. These results suggest selective amino acid transport in mammary tissue during lactation. PMID- 11787712 TI - Negative balance of calcium during lactation in marginally nourished women. AB - Thirty-three rural Mexican women (age, 18-36y; weight, 50.3+/-3 kg; height, 148.3+/-2 cm) were studied under metabolic balance conditions. The objectives were to study the metabolic balances of calcium and phosphorus at the 1st, 3rd, and 6th months of lactation and postweaning and to determine the incorporation of calcium and phosphorus in milk. Subjects were divided into 5 groups of 5 to 10 each, representing: the 1st, 3rd, and 6th month of lactation, postweaning, and a control group of nonpregnant, nonlactating women. Metabolic balance was determined using identical diets and analysis of 24-hour urine (3 d), 72-hour feces, and 24-hour milk samples. Calcium content was determined by atomic absorption spectrophotometry and phosphorus by a colorimetric method. Calcium content in milk was similar at the 1st, 3rd, and 6th months. Positive calcium balances were observed in the control group, while balances were very negative in all lactation groups (-721.6+/-248 mg/d). Calcium urinary excretion was higher in the control and postweaning groups (P < 0.05), suggesting a regulatory mechanism to conserve calcium during lactation. No differences were observed in phosphorus content in milk at the 1st, 3rd, and 6th months. Positive balances were observed in the control and postweaning groups (331+/-139 and 87.1+/-130 mg/d, respectively, mean +/- SD), while the lactation groups presented more subjects (approximately 75%) in negative balance (mean +/- SD of -180.6+/-392 to -439+/ 146 mg/d). High fecal calcium and phosphorus excretion (approximately 1,500 mg/d) likely contributed to the negative balance during lactation. PMID- 11787713 TI - Do healthy very-low-birth-weight infants fed on their own mothers' milk require sodium supplementation? AB - Sodium and potassium levels were measured weekly in mothers' milk and in serum and urine of 41 supplemented and 25 unsupplemented very-low-birth-weight infants whose mean birth weights were 1390g and 1332g, respectively (mean gestational age, 31 weeks). Sodium intake was 5.95mmol/kg/day for the supplemented group and 2.75mmol/kg/day for controls. None of the infants in either group was hyponatremic during the 6-week period of study. Urinary sodium in the supplemented group was 15.7mmol/L as compared with 7.5mmol/L in controls. Human milk sodium was significantly lower than reported elsewhere. Growth in the supplemented group was greater than in the unsupplemented group. Since no episode of hyponatremia occurred, it was concluded that routine sodium supplementation was unnecessary. PMID- 11787714 TI - Overview: the future of research in human milk. PMID- 11787715 TI - From bioactive substances to research on breast-feeding promotion. AB - Despite known health benefits, exclusive breast-feeding for at least 4 months is uncommon in many countries. In Mexico, most mothers initiate breast-feeding but few breast-feed exclusively. OBJECTIVE: The objective was to examine the effectiveness of home visits by lay peer counselors to increase exclusive breast feeding among mothers in a periurban area of Mexico. METHODS: An ethnographic assessment conducted in 1994 that identified key maternal beliefs, practices, and needs was used to guide educational strategies. Lay counselors were recruited from the same community and trained by La Leche League. From March 1995 through September 1996, pregnant women were identified by community census and invited to participate. Women were enrolled into a randomized, controlled study of 3 groups: no intervention (control), 3 visits, and 6 visits during pregnancy and early postpartum. Data collection was performed by a social worker apart from the counselors. Exclusive breast-feeding was defined by WHO criteria. RESULTS: The study enrolled 130 women; 52 were in the 3-visit group, 44 in the 6-visit group, and 34 in the control group. Study groups did not differ in the maternal characteristics or initiation of breast-feeding (96%). At 3 months postpartum, exclusive breast-feeding was practiced by only 12% of controls vs. 52% in the 3 visit group and 67% in the 6-visit group (P < 0.001, log rank test). In the first 3 months, significantly (P = 0.037) fewer intervention than control infants had an episode of diarrhea (11% vs. 26%, respectively). Intervention effectiveness was independent of maternal factors or birth hospital. CONCLUSIONS: This unique experimental study demonstrated a dramatic increase in exclusive breast-feeding and a significant reduction in infant illness in an urban community through well designed maternal support including early intervention and repeated contact. PMID- 11787716 TI - Protective role of human lactoferrin against invasion of Shigella flexneri M90T. AB - Lactoferrin is an iron-binding protein found in human mucosal secretions such as milk. A variety of functions have been ascribed to this protein, it appears to contribute to antimicrobial host defense. Still its overall physiological role remains to be defined. We sought to study the role of recombinant human lactoferrin (rhLf) in Shigella infection. Invasion of epithelial cells is essential to the development of bacillary dysentery. Shigella flexneri 5 M90T, a virulent strain, was evaluated in the classic HeLa cell invasion model, in immunoblots, and by transmission electron microscopy, immunofluorescence, and deconvolved microscopy Bacteria not exposed to rhLf were used as controls. We found that rhLf decreased significantly the invasiveness of S. flexneri 5 M90T in a HeLa cell model. The immunoblot data showed that invasion plasmid antigen B (IpaB) was released from the bacteria during incubation with rhLf. Lactoferrin treatment did not directly dissociate the complex of IpaB and IpaC (IpaBC) once the complex had been formed. Furthermore, ferric iron had no effect on release of IpaB. Electron microscopy of rhLf-treated bacteria suggested a reduction in vacuolization of the HeLa cell cytoplasm and decreased number of bacteria within HeLa cells. At 40,000 x magnification the few rhLf-treated Shigella that invaded exhibited a dense ring completely surrounding them. Immunofluorescence and deconvolved microscopy suggested that rhLf-treated bacteria were completely surrounded by a thick layer of actin. The fact that two cell surface functions (invasion and actin-mediated movement) were deranged suggests that rhLf disrupts the integrity of the bacterial outer membrane in which virulence proteins are anchored. The mechanism by which rhLf impairs Shigella invasiveness may be relevant to other enteropathogens that share similar virulence strategies. PMID- 11787717 TI - Binding of transcobalamin II by human mammary epithelial cells. AB - The presence of nutrient binders in milk may have an important role during milk production and may influence the nutrient's bioavailability to the infant. Human milk and plasma contain at least two types of vitamin B12 binders: transcobalamin II (TCII) and haptocorrin (Hc). Vitamin B12 in milk is exclusively bound to Hc (Hc-B12). In plasma, the major vitamin B12 binding protein that is responsible for delivering absorbed vitamin B12 to most tissues and cells is TCII (TCII-B12). Currently, little is known about the route of secretion of vitamin B12 into human milk. It is possible that a receptor-mediated pathway is involved, since maternal vitamin B12 supplementation increases the amount of the vitamin secreted into human milk if the mother's vitamin B12 consumption is low, but remains unchanged if her intake is adequate. In this study, we investigated the process by which the mammary gland acquires vitamin B12 from maternal circulation, whether as a free vitamin or as a Hc-B12 or TCII-B12 complex. TCII was purified from plasma incubated with [57Co]vit B12 (B12*), while Hc was purified from whey incubated with B12*. Both proteins were separated by fast protein liquid chromatography using gel filtration and anion-exchange columns. Purity of the separated proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies were carried out on a monolayer of normal human mammary epithelial cells (HMEC) at 4 degrees C using free B12* and TCII-B12* and Hc-B12* complexes. Minimal binding of free B12* and Hc-B12* to HMEC was observed; however, HMEC exhibited a high affinity for the TCII-B12* complex. This study suggests that a specific cell surface receptor for the TCII-B12 complex exists in the mammary gland. It is possible that once vitamin B12 is in the mammary gland it is transferred to Hc (which may be synthesized by the mammary gland) and then secreted into milk as a Hc-B12 complex. PMID- 11787718 TI - Drug transport into milk. PMID- 11787719 TI - Diet, growth, and bone mineralization in premature infants. AB - Energy, protein, and mineral requirements in premature infants are high, hence increasing the risk of poor growth and development of metabolic bone disease. This double-blind study included 127 consecutive premature infants with gestational age below 32 weeks. Both sick and healthy infants participated. Average duration of ventilator treatment: 2 days, CPAP treatment: 10 days (range, 0-50d). Infants were randomized to 3 groups from 1 week old to 37 weeks of gestational age and fed the following: a) human milk (their own mother's milk or banked milk) supplemented with phosphate, b) human milk fortified with protein, calcium, and phosphate, or c) unsupplemented mother's milk or preterm formula. Infants randomized to preterm formula were fed formula only if their own mother's milk was not available, hence there were 2 subgroups of infants fed either unsupplemented human milk or preterm formula. Volume of intake was 191+/ 14mL/kg/d (mean +/- SD); linear growth was measured weekly by knemometry; head circumference was measured weekly; and growth rate was calculated by linear regression for each infant. Bone mineralization and body composition were measured by DEXA-scan (Hologic 1000/W) at term. There was a tendency toward slower growth and less bone mineral content in infants fed unsupplemented human milk but, surprisingly, the difference was small and not significant. PMID- 11787720 TI - Fat content and fatty acid composition of fresh, pasteurized, or sterilized human milk. AB - In hospitals, human milk is subjected to heat treatment to reduce risk of transmission of infectious agents such as human immunodeficiency virus (HIV), hepatitis B, cytomegalovirus, and bacterial contamination, especially during feeding of banked milk to preterm infants. Fat losses due to heat treatment have been extensively studied in cow milk but have received little attention in human milk. We studied the effect of human milk pasteurization and sterilization on total fat content available to the infant as well as on fatty acid composition. Milk samples from 12 mothers (days 5-35 of lactation) were divided into three equal parts: one remained fresh, one was pasteurized (62.5 degrees C for 30min), and one was sterilized (120 degrees C for 30min). Fat content was determined gravimetrically, and the contribution of 30 fatty acids was determined by gas chromatography. For investigation of loss of available fat in sterilized milk, milk was collected from two additional mothers and analyzed with a modified extraction method. Total fat content was the same in fresh, pasteurized, and sterilized milk. The available fat content was 3.1+/-0.4g/dL (mean +/- SE) in fresh human milk, 3.1+/-0.4g/dL in pasteurized human milk, and 2.7+/-0.3g/dL (P < 0.001 vs. fresh) in sterilized human milk because of formation of a surface skin and fat adherence to the vial wall after sterilization. The fatty acid composition of 10 saturated, 10 monounsaturated, and 10 polyunsaturated fatty acids of both the n6 and n3 series was not affected by pasteurization. In sterilized milk there was a slight decrease of linoleic acid (C18:2n6; -0.7% vs. fresh; P = 0.006) and arachidonic acid (C20:4n6; -2.5%; P = 0.045). Pasteurization and sterilization do not affect total fat content of human milk, but sterilization may reduce available fat content by >10%. Fatty acid composition of human milk is not changed by pasteurization, but is slightly changed by sterilization. PMID- 11787721 TI - Lymphocyte subpopulations in breast-fed and formula-fed infants at six months of age. AB - Factors such as cytokines and lymphocytes present in human milk can influence the developing immune system. This suggests an immunoregulatory role for human milk that is absent in infants consuming formula. There are very few data available from well-defined groups of breast-fed and formula-fed infants with regard to their immune status as reflected by lymphocyte immunophenotypic values. The aim of this study was to investigate the potential difference in lymphocyte subsets between breast-fed and formula-fed infants at 6 months of age. Blood samples were taken by venipuncture. Lymphocytes were analyzed by 2-color direct immunofluorescence with Becton Dickinson Immunocytometry Systems SimulSET reagents (BD, Franklin Lakes NJ). There were 73 breast-fed infants and 55 formula fed infants at 6 months of age. The frequency of natural killer (NK) cells (CD3 /CD16+ + CD56+) was greater in breast-fed infants (9.2%) than in formula-fed infants (6.6%, P < 0.001), while the CD4 to CD8 ratio was 2.8 in breast-fed infants compared with 3.4 in formula-fed infants (P < 0.001). CONCLUSION: Breast fed infants (<250mL formula/bovine milk per week) had a greater proportion of NK cells and a lower CD4 to CD8 ratio than formula-fed infants at 6 months of age. PMID- 11787722 TI - Trends in donor milk banking in the United States. AB - Modern donor milk banking was conceived in the US in the early 1900s as a medicalized version of wet nursing. Over the course of the century the fortunes of donor milk banking have varied considerably. In the last 20 years donor milk banking has been negatively affected by the development of specialty formulas, safety issues related to viral transmission, and lack of clinical research. To survive, US milk banks have been receptive to clinical uses considered as "alternative medicine," and have cooperated with governmental agencies to develop standards for safety. A qualitative analysis of collected case histories of US donor milk recipients demonstrates that donor human milk banking can be critical to survival and the well-being of at-risk infants, children, and the occasional adult. By analyzing national data collected by survey method and examining the literature, the researcher compared German and US milk banks and distribution data. German milk banks use donor milk exclusively for premature infants and have less stringent operating standards, yet dispense volumes of milk greatly in excess of the US milk banks. While statistics are lacking for the total recipient population in the US, a projected analysis (based on German consumption) of the potential volume that could be dispensed in the US is presented, indicating that the population in need of this crucial public health service is currently under served in the US. PMID- 11787723 TI - Bacterial toxins and enteral feeding of premature infants at risk for necrotizing enterocolitis. AB - Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin 6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). Escherichia coli, Klebsiella, Enterobacter, and Clostridium spp, identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates with Clostridium spp most strongly associated with NEC disease. Stool filtrate endotoxin (endotoxin units [EU] per gram) measured by a Limulus amebocyte lysate assay was age-dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (>10 ln EU/g) compared with NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the enzyme linked immunosorbent assay (ELISA) for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or II NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies for patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates. PMID- 11787724 TI - Epidemiology of breast-feeding in Italy. AB - To evaluate the prevalence of breast-feeding in Italy and to describe the social and environmental factors associated with its practice, 1601 mothers were systematically recruited as representative of deliveries across all regions of Italy during November 1995. They were interviewed in March, June, and September of 1996. Interviews were conducted by telephone using a standardized questionnaire designed for computer scanning. The results indicated that 85% of mothers breast-fed their infants. The rates of breast-feeding at 3, 6, and 9 months were, respectively, 51%, 32%, and 19%. Among the 830 lactating mothers at 3 months, 72% practiced breast-feeding "on demand." Pediatricians, midwives, and gynecologists were the main sources of information about breast-feeding, but 43% of the mothers did not receive any information. Media (radio, TV) were mentioned as sources of information by only 2% of the mothers. Maternal factors significantly associated with breast-feeding and its duration were: a) having been breast-fed as infants, b) being nonsmokers, and c) being given information about lactation at the time of discharge from their hospital ward. Maternal characteristics (age, weight, and height), parental socioeconomic indicators (profession and education), and neonatal care (rooming-in practice) were not significantly associated with breast-feeding. Our results show that in Italy a fairly high percentage of mothers start breast-feeding and that both maternal factors (history and habits) and good information may support its duration. PMID- 11787725 TI - Analysis of casein using two-dimensional electrophoresis, western blot, and computer imaging. AB - Casein from milk of 20 mothers, 8 weeks postpartum, was analyzed using 2 dimensional electrophoresis. The casein micelle under 2-D denaturing conditions gives approximately 15 major spots. Beta-Casein, kappa-casein, para-kappa-casein, and casein peptides can be tentatively identified by molecular size, isoelectric point, and spot shape characteristics. All spots are not present in all samples. Two spots thought to represent different phosphorylated forms of beta-casein were selected for area and density measurements by means of the NIH-Image program. The larger area at approximately 26 kDa, isoelectric point 5.3, consisted of 1 to 3 closely linked spots, perhaps reflecting phenotype. The smaller spot 24kDa, isoelectric point 5.4, was always a single unit. Visual scanning of gels suggests a wide range of casein concentration. Computer comparison will allow a statistical analysis. PMID- 11787726 TI - Consumption of lipophilic contaminants in human milk by infants: quantities are usually incorrect. AB - We evaluated several reports on the detection of nitromusks (artificial perfumes) in human milk. The nitromusks found were separated by gas-liquid chromatography and identified by mass spectrometry. However, the quantities reported as being consumed by infants were often questionable (Jensen, 1995). The investigators did not always a) obtain a representative samples of milk, b) extract and quantify the fat by a recognized, accurate method, or c) determine the amount of milk, hence fat, consumed by the infant. Some investigators gave almost no data on the milk, except to say that a sample was obtained. Reports on some other contaminants in human milk were similarly deficient. We have published a description of recommended extraction procedures in a paper presenting a detailed protocol for the processing of milk so as to determine the actual amounts of lipophilic contaminants ingested by the nursing infant (Jensen et al. 1997). PMID- 11787727 TI - Active transport of nitrofurantoin into rat milk. AB - Most xenobiotics are transferred into milk by passive diffusion; however, some drugs have been reported to accumulate in milk as a result of active transport. In the present study, lactating Sprague Dawley rats were used to characterize the transfer of nitrofurantoin into milk. The observed milk to serum concentration ratio (M/S) of 31.1+/-4.0 was 100 times higher than the M/S predicted by diffusion (0.3+/-0.1), indicative of an active transfer into milk. Randomized crossover infusions of nitrofurantoin (0.5mg/h) in the absence and presence of a cimetidine infusion regimen (15mg/h) resulted in the corresponding mean M/S of 29.5+/-5.4 vs. 30.7+/-5.0 and systemic clearance (Cls) of 2.7+/-0.7 vs. 2.2+/-0.4 L/h/kg, respectively. Nitrofurantoin infusions (0.5mg/h) in the absence and presence of a higher cimetidine infusion regimen (30mg/h) resulted in the corresponding mean values for M/S of 23.0+/-7.7 vs. 19.8+/-5.9 and Cls of 2.8+/ 0.4 vs. 1.4+/-0.4L/h/kg, respectively. Only the decrease in Cls at the higher cimetidine infusion was statistically significant. These observations provide evidence that nitrofurantoin is actively transported into rat milk by a transporter that is not inhibited by cimetidine. These data suggest the presence of at least two distinct mammary epithelial transporter systems, one that transports organic cations (e.g., cimetidine) and another for anions (e.g., nitrofurantoin). PMID- 11787728 TI - Influence of lysine on cimetidine uptake and on excretion of cimetidine by the rat mammary gland. AB - Cimetidine is actively transported into human and rat milk. However, the transporters involved have not been characterized. It is possible that xenobiotics may be actively transported into milk by an amino acid transport system. The objective of these studies was to determine the influence of lysine on the uptake of cimetidine into rat mammary explants (study 1), and on the excretion of cimetidine into rat milk (study 2). In study 1, excised lactating rat mammary epithelial tissue fragments were exposed to 3H-cimetidine and 14C lysine in the presence of 10 microM, 1 mM, or 1 M cold lysine, and the uptake of 3H-cimetidine and 14C-lysine were measured by liquid scintillation counting after 5 or 20 minutes of incubation. After 5 minutes of incubation, 1 M lysine inhibited 3H-cimetidine uptake by 47.7% (SD +/- 6.5%), compared with 10 microM lysine (P < 0.05), and 14C-lysine uptake was also inhibited by 54.1% (SD +/- 6.4%) (P < 0.05). Similar results were seen after 20 minutes of incubation. In a randomized crossover study (study 2), 6 lactating female rats were infused to steady state with cimetidine (0.5mg/h) in the presence or absence of lysine (360mg/h). Cimetidine concentrations in serum and milk were determined by high performance liquid chromatography. Cimetidine systemic clearance (28.6+/ 15.0mL/kg/min vs. 38.9+/-3.9 mL/kg/min, mean +/- SD) and milk to serum cimetidine ratio (M/S) (28.0+/-16.1 vs. 28.9+/-6.7), respectively, were not significantly altered by the presence or absence of lysine. Although 1 M lysine inhibited uptake of cimetidine in rat mammary explants, the concentrations of lysine used in this study, which approached toxicity in vivo, produced no significant effects on cimetidine transport into milk or the systemic clearance of cimetidine. PMID- 11787729 TI - The effect of pasteurization on transforming growth factor alpha and transforming growth factor beta 2 concentrations in human milk. AB - Transforming growth factor alpha (TGF-alpha) and beta 2 (TGF-beta2) are present in human milk and are involved in growth differentiation and repair of neonatal intestinal epithelia. Heat treatment at 56 degrees C has been shown effective for providing safe banked donor milk, with good retention of other biologically active factors. The purpose of our study was to determine the effect of heat sterilization on TGF-alpha and TGF-beta2 concentrations in human milk. Twenty milk samples were collected from 20 lactating mothers in polypropylene containers and frozen at -20 degrees C for transport or storage. Before heat treatment by holder pasteurization, the frozen milk was thawed and divided into 1-mL aliquots. All samples were heated in an accurately regulated water bath until a holding temperature was achieved, then held for 30 minutes using constant agitation. Holding temperature ranged from 56.5 degrees C to 56.9 degrees C. The milk was then stored at 4 degrees C overnight for analysis the following day. The concentration of TGF-alpha was measured by radioimmunoassay. Mean concentration +/- SD of TGF-alpha in raw milk samples was 119+/-50 pg/mL, range 57 to 234. The mean concentration +/- SD of TGF-alpha in heat treated samples was 113+/-50 pg/mL, range 51 to 227. TGF-alpha concentration was minimally affected by pasteurization, with an overall loss of 6.1%. Of 19 samples, 4 had increased and 15 had decreased concentrations after pasteurization (mean percent SEM: 94%+/-7% of raw milk, range 72%+/-107%). The concentration of acid-activated TGF-beta2 was measured by enzyme-linked immunosorbent assay. Mean concentration +/- SD of TGF beta2 in raw milk samples was 5624+/-5038 pg/mL, range 195 to 15480. The mean concentration +/- SD of TGF-beta2 in heat-treated samples was 5073+/-4646 pg/mL, range 181 to 15140. TGF-beta2 survived with relatively little loss (0.6%): of 18 samples, 11 had increased and 7 had decreased concentrations after pasteurization (mean percent +/- SEM: 99.4+/-6.7% of raw milk, range 79%-120%). In conclusion, both TGF-alpha and TGF-beta2 were well-preserved in whole milk after holder pasteurization at 56.5 degrees C. The relative increase in growth factor concentration in some of the samples may be attributable to the release of that factor from the cellular and/or fat compartments into the aqueous fraction of human milk. These findings have implications regarding use of donor milk as an alternate source of growth factors and cytokines for the newborn gut when mother's milk is unavailable. PMID- 11787730 TI - Can women remember when their milk came in? AB - The perception of the timing of milk arrival has been identified as an important predictor of breast-feeding success. Because this indicator has the potential to be used as a proxy for the onset of lactogenesis stage II and is relatively simple to measure, it is possible to include it as part of large-scale surveys. It is unknown, however, how likely women are to recall the timing of milk arrival accurately, several months after delivery. To test the validity of maternal recall, we conducted a longitudinal study in Hartford CT with 192 women who delivered healthy, term singletons at Hartford Hospital. All women were interviewed daily from day 1 postpartum until they perceived that milk arrival had occurred. Seven months after delivery, women were able to recall if their milk came in late (i.e. >72h postpartum) with a high level of sensitivity (93.6%) and an acceptable level of specificity (62.5%). PMID- 11787731 TI - Glycosidase activities and sugar release in human milk. AB - Human milk glycosidic enzymes and biologically active glycoconjugates incubate together in the breast between the time of synthesis of milk and the next feed, and during storage of expressed milk. The degree to which the glycoconjugates of human milk are modified by glycosidases was investigated. Human milk was freshly obtained in the laboratory from four women. The activities of alpha-L-fucosidase, alpha-D-galactosidase, beta-D-galactosidase, beta-glucosidase, N-acetyl-beta hexosaminidase, beta-D-glucuronidase, and neuraminidase in were determined; fucosidase and hexosaminidase displayed the highest activity. Free fucose, N acetylneuraminic acid (NANA) and N-acetylhexosamines were also measured by gas chromatography and gas chromatography/mass spectroscopy. Incubation of milk samples for 2 to 16 hours at 37 or 20 degrees C, but not at 4 degrees C, increased the amounts of fucose, NANA, and N-acetylhexosamines, consistent with enzymatic release by the endogenous glycosidases. The milk contained small amounts of free sugars, whose concentrations were used to determine the upper limits of postsynthetic modification of glycoconjugates during the residence time of milk in the breast of these four donors. These data indicate that under typical conditions glycoconjugate degradation in milk is modest. PMID- 11787732 TI - The transforming growth factors beta in development and functional differentiation of the mouse mammary gland. AB - The transforming growth factors beta (TGF-beta) are multifunctional regulators with diverse effects on a variety of developmental processes and differentiated functions. In the mammary gland, a considerable amount of evidence has accumulated indicating that TGF-beta plays a critical role during several phases of the mammary cycle. TGF-beta regulates growth and patterning of the mammary ductal tree in the virgin mouse. During pregnancy, TGF-beta is required for alveolar development and functional differentiation, while at the same time inhibiting secretion of milk proteins. At parturition this inhibition is lifted, permitting initiation of lactation. PMID- 11787733 TI - Is milk a conduit for developmental signals? AB - The diverse role of milk in the neonate is slowly expanding beyond nutritional and immunological borders to include possible developmental roles for the numerous hormones and growth factors found in this medium. Yet, despite the growing list of milk-borne factors, the precise impact of each of these on the neonate remains to be elucidated. The focus of this review is to summarize studies from our laboratory which demonstrate clearly that milk-borne factors play an obligatory role in the postnatal development of at least one organ, the anterior pituitary gland. PMID- 11787734 TI - Regulation of cell apoptosis by insulin-like growth factor I. AB - Correct temporal and spatial regulation of apoptosis is critical for normal mammary gland development and lactation. Previous work with a strain of transgenic mice that overexpress des(1-3)hIGF-I during pregnancy and lactation suggested that this growth factor inhibits apoptosis. The hypothesis tested within these studies is that overexpression of des(1-3)hIGF-I within the mammary gland inhibits apoptosis and the expression of apoptosis-associated genes that are known to be activated by the transcription factor AP-1. This inhibition of apoptosis was further posited to predispose the tissue to carcinogenesis. TUNEL analysis of mammary tissue from transgenic mice that overexpress des(1-3)hIGF-I under control of the rat whey acidic protein promoter showed only 25% (P < 0.05) of the number of apoptotic cells found in nontransgenic mice at the same stage of lactation. Northern analysis of RNA from these animals showed a 75% (P = 0.08) reduction in c-Jun mRNA abundance. Histological analysis of mammary tissue from nonlactating multiparous WAP-DES mice ranging in age from 13 to 25 months showed a variety of hyperplastic lesions. These lesions aberrantly expressed the transgene. At 23 months of age 50% of the transgenic mice within this study developed adenocarcinomas. These results support the conclusion that inhibition of apoptosis within the mammary gland by IGF-I involves decreased activity of AP 1 and predisposes the tissue to tumors. PMID- 11787735 TI - Human milk contains detectable levels of immunoreactive leptin. AB - Leptin, the recently cloned product of the obese (ob) gene, is a 16 kDa-protein that acts as a circulating satiety factor. It also serves to regulate energy expenditure and may act as a counter regulatory hormone to insulin. Initially thought to be exclusively produced by mature adipocytes, its mRNA has now been identified in significant levels in the placenta as well as the fetus raising speculation regarding its importance as a growth factor. Given studies demonstrating that exclusively breast-fed infants are leaner due to decreased energy intakes than formula-fed infants, we hypothesized that the presence of leptin in human milk could participate in mediating the earlier satiety of those infants fed human milk. We undertook this initial study to qualitatively examine the presence of leptin in human milk utilizing an immunoblot approach. Random milk samples during the first 2 weeks of lactation were available for study from 4 mothers delivering at term. Milk samples were centrifuged, the aqueous layer removed, and the protein content quantitated. One-hundred micrograms of total protein were separated by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis (SDS-PAGE), transferred to nitrocellulose, and immunoblotted with an antileptin antibody. As controls, recombinant human leptin alone and a sample of milk containing added leptin were similarly electrophoresed and immunoblotted. Labeled proteins were visualized by chemiluminescence. Significant amounts of leptin protein were identified in all milk samples examined. No difference in protein detection was identified in fresh milk vs. frozen milk, and little difference was apparent in foremilk samples vs. hindmilk samples. These preliminary data reveal the presence of leptin in term human milk and suggest that further studies to document bioactivity of milk-derived leptin are warranted. PMID- 11787736 TI - Induction of expression of branched-chain aminotransferase and alpha-keto acid dehydrogenase in rat tissues during lactation. AB - This study was designed to determine the effect of lactation and weaning on the gene expression of branched-chain aminotransaminase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD) in different tissues of the lactating rat. BCAT activity increased in mammary tissue during lactation and was 6-fold higher than in virgin rats. This increase was associated with an increase in protein levels measured by immunoblot analysis, and with an increase in BCAT mitochondrial (BCATm) mRNA concentration. Twenty-four hours after weaning, BCAT activity, protein concentration, and mRNA levels in the dam decreased. BCAT activity, protein enzyme levels, and BCATm mRNA concentration in muscle were higher in weaning rats than in lactating rats. BCAT cytosolic (BCATc) mRNA was not expressed in mammary tissue, and there was no BCATc enzyme detected by Western blot in any physiological state. Mammary tissue BCKD activity increased and was active (dephosphorylated) during the lactation period. The level of enzyme also increased and the mRNA level for the E2 subunit in mammary tissue was 10-fold higher than the virgin values. Hepatic enzyme activity increased during weaning, and this was associated with the protein level and with the mRNA level of the E2 subunit. Muscle BCKD activity and protein content were the lowest of all tissues, and the E2 subunit mRNA level was barely detected by Northern blot analysis. The results suggest gene regulation of the two main catabolic enzymes of the branched-chain amino acid metabolism during lactation. PMID- 11787737 TI - Ocular complications of needle perforations during retrobulbar and peribulbar injections. AB - As a whole, the complication rate of retrobulbar and peribulbar injections is low, especially if done correctly (see appendix I). Side effects, however, can be extremely serious, and alternative methods such as topical or sub-Tenon's anesthesia should be considered (see appendix II), particularly when evaluating monocular patients with high-risk characteristics. PMID- 11787738 TI - Prevention of posterior segment complications of phacoemulsification. AB - The prevention of posterior segment complications of cataract surgery depends on the maintenance of an intact lens capsule and zonular apparatus. The phacoemulsification techniques presented here, including cortical cleaving hydrodissection, hydrodelineation, ultrasound power modulation, and management of the epinucleus and cortex, together with the special techniques presented for management of small pupils and compromised zonule, minimize the risk of damage to the posterior capsule by maximizing control of nuclear disassembly and evacuation. Choo-choo chop and flip phacoemulsification, in particular, provides a management strategy for cataracts of all grades of nuclear hardness whether in the presence of a small pupil or compromised zonule. PMID- 11787739 TI - Cataract surgery in previously vitrectomized eyes. AB - Because of the application of vitreoretinal surgical techniques to a broader range of posterior segment diseases and because cataract develops frequently in postvitrectomy eyes, cataract surgeons should be familiar with the challenges of cataract extraction in vitrectomized eyes. The cataract surgeon can prepare for these challenges with awareness of such potential factors as an excessively mobile posterior capsule, possible need for vitrectomy equipment, and special considerations concerning intraocular lens selection and power calculation. Knowledge of ocular comorbidities will help the cataract surgeon to counsel the patient appropriately and will help the patient to form realistic expectations. Despite the challenges it presents, cataract extraction in postvitrectomy eyes is usually associated with favorable visual outcomes. PMID- 11787740 TI - Phototoxic retinopathy. AB - Although the occurrence of iatrogenic light-induced retinal toxicity is beyond doubt, several issues remain to be studied further. These include conflicting reports regarding the wavelength of light that is most hazardous; what mechanism contributes more significantly in the pathogenesis of light-induced retinal toxicity-photochemical or photothermal; why does it occur in only some patients; and what is the protective role of UV absorbing chromophores in intraocular implants. Nevertheless, it is important for all ophthalmic surgeons to be aware of this complication and take measures that could decrease the risk of its occurrence. PMID- 11787741 TI - Gentamicin and other antibiotic toxicitiy. AB - Antibiotics have the potential to cause significant ocular toxicity when they gain access to the inside of the eye. The aminoglycosides, in particular gentamicin, are the most toxic of the antibiotics commonly used in ophthalmology. Extreme caution should be used when administering a periocular injection of aminoglycoside for treatment or prophylaxis of infection. Intraocular injection of aminoglycoside for gram-negative coverage in endophthalmitis management has been replaced in most cases by ceftazidime. Ceftazidime provides excellent coverage against gram-negative bacteria with less potential for retinal toxicity at therapeutic dosages. Experimental and clinical studies have shown that intraocular vancomycin is safe and effective treatment against gram-positive organisms causing endophthalmitis. A combination of ceftazidime and vancomycin provides broad-spectrum coverage for virtually all bacteria causing endophthalmitis and is the current intraocular treatment of choice. PMID- 11787742 TI - Diabetic maculopathy and cataract surgery. AB - Patients with diabetic mellitus have an increased risk of developing cataract. Many such patients have pre-existing diabetic retinopathy at the time of cataract surgery Although more than 90% of the patients who have no pre-existing diabetic retinopathy carry a good visual prognosis and eventually have 20/40 or better visual acuity, nearly one-third of patients with pre-existing retinopathy may show retinopathy progression. Postoperative angiographic macular edema is more common in patients with diabetes but resolves spontaneously in patients with no or minimal diabetic retinopathy. In patients with moderate to severe NPDR or more, clinically significant macular edema tends to persist, may arise de-novo, or even worsen after cataract surgery. Patients with diabetes need a preoperative characterization of their retinopathy and a thorough discussion with the patient about the need for cataract surgery, and the risk of progression of retinopathy is mandated. Currently, early surgery is favored before the development of significant diabetic retinopathy rather than wait for the cataract to become denser. All efforts should be made to stabilize diabetic retinopathy with appropriate laser treatment before cataract surgery. All diabetic patients need close observation for at least 6 months following surgery to intervene with laser photocoagulation as and when required to prevent visual loss from diabetic maculopathy and other consequences of diabetic retinopathy. PMID- 11787743 TI - Choroidal detachment and expulsive choroidal hemorrhage. AB - ECH occurring during open globe surgery is no longer synonymous with loss of the eye. If the eye is closed immediately (i.e., the hemorrhage does not become expulsive) and modern secondary reconstruction techniques are applied, the prognosis is good. Prophylaxis, however, is the ultimate goal, achieved by a conscious consideration of all risk factors and planning of the surgical intervention accordingly ECH nevertheless can occur, for which the surgeon must be mentally prepared and then act swiftly, based on a previously designed strategy. All ophthalmologists performing (especially open globe) surgery should remain alert. Although new techniques such as small, self-sealing incisions and phacoemulsification have lowered the ECH risk, it is still not zero. (3,44,71) Once the wound is closed and the bleeding has stopped, maneuvers such as drainage or even proceeding with the original surgery can be considered, but the risks of such a course must be carefully analyzed first. Comprehensive secondary reconstruction is best placed in the hands of specialists. PMID- 11787744 TI - Postcataract cystoid macular edema. AB - Ocular tissues, like those of other organs, exhibit well-defined morphologic reactions to local trauma and insult in the form of hyperemia, vasodilation, increased permeability of blood vessels, and edema. Cystoid macular edema (CME) following cataract surgery is one such manifestation, and it can result in either temporary, or rarely, a permanent reduction of visual acuity. Although its cause remains obscure, the relationship of CME to the details of the surgical procedures and their complications are becoming clearer. Likewise more insight into the phenomenon is being imparted by the agents being used in the preventative or curative line of management in CME. PMID- 11787745 TI - Endophthalmitis following cataract surgery. AB - This article is an attempt to review the latest advances in recognition, treatment, and prevention of postcataract extraction endophthalmitis. PMID- 11787746 TI - Retained lens fragments after cataract surgery. AB - In conclusion, the incidence of retained lens fragments appears to have increased in recent years. The timing of vitrectomy can be delayed to permit improvement of corneal edema, ocular congestion, and acute postoperative inflammation. Placement of a posterior chamber intraocular lens at the time of the initial cataract surgery does not adversely affect final visual results. Retinal detachment is a frequent adverse event in these eyes. Vitrectomy and removal of retained lens fragments restores good visual acuity and reduces secondary glaucoma in the majority of patients. PMID- 11787747 TI - Management of dislocated intraocular implants. AB - Implant dislocation may occur in the absence of appropriate capsular or zonular support (PCIOL) (11,35,53) or following traumatic injury to anterior ocular tissues (ACIOL). (11,19,20) Other factors (e.g., advanced patient age, high myopia, previous vitrectomy, pseudoexfoliation syndrome, and certain connective tissue disorders) also may predispose implant dislocation. (9,52) Although reported for all types of IOLs, implant dislocation is becoming more manageable because of the advancement of surgical techniques. A dislocated ACIOL or PCIOL may be explanted, exchanged, or repositioned. (11,48,71) Repositioning the dislocated PCIOL in the ciliary sulcus with modern vitreoretinal techniques provides an optimal environment for visual recovery. (11,71) Implant repositioning techniques generally may be categorized into the external or the internal approaches. (8,11) The former involves external suturing methods for a primary or secondary implant in the absence of adequate capsular or zonular support (15,16,31,42,56,60,61,64,66,73,76) and the latter is achieved through modern pars plana techniques. 8,11,62,69) Recently, several implant repositioning methods gaining increasing acceptance include the scleral loop fixation, (45) the snare approach, (43) the use of the 25-gauge implant forceps, (13) temporary haptic externalization, (8,11,36,71) and the use of perfluorocarbon liquids. (1,28,40,41,44) The temporary haptic externalization method combines the best features of the external and the internal approaches, avoids complex intraocular maneuvers, and allows precise scleral fixation of the dislocated IOL on a consistent basis. (8,11,71) Endoscopy provides the surgeon with optimal viewing of the anterior retropupillary anatomy that is often difficult to appreciate (e.g., capsular-zonular complex, ciliary sulcus, anterior retina, and vitreous base). (6,11) As a result, precise haptic placement is possible during the repositioning process. (6,11) However, a three-dimensional birds-eye view is lacking, and there may be a steep learning curve with endoscopy. (11) Certain characteristics of a silicone plate implant may enhance implant dislocation. (11,33,34,46,49,58) Capsular contraction following an Nd:YAG posterior capsulotomv may result in a posterior dislocation of the silicone plate implant. (11,33,34,46,49,50,58) Special techniques are available for the retrieval of the slippery dislocated silicone plate implant from the retinal surface without causing injury. (33,58) Repositioning the plate implant anterior to capsular remnants or in the ciliary sulcus may lead to recurrent dislocation, and its removal is frequently the best option. (11) Placing a second implant in the presence of a disLocated implant is ill advised because subsequent surgical management becomes more complex. (11) Surgical options include removing the dislocated implant through a Limbal or pars plana incision with special techniques, (74,75) repositioning the dislocated implant after removing the second implant," and explanting both implants. (11) Considering the increased morbidities and complications associated with the management of double implants, the surgeon should avoid the placement of a second implant in the setting of a dislocated implant. (11) PMID- 11787748 TI - Retinal detachment. AB - RD is a serious and well-known complication after cataract surgery, developing in 1% to 3% of all patients undergoing cataract extraction. High myopia, disruption of the posterior capsule intraoperatively or postoperatively by Nd: YAG laser, and vitreous loss increases the risk for RD. Retinal evaluation with detailed indirect ophthalmoscopy with scleral indentation and prophylactic treatment to all lesions that contribute to retinal tear and RD is strongly advocated before cataract surgery and Nd: YAG laser capsulotomy. Intraoperative vitreous loss should be managed meticulously, and these patients should be examined more frequently in the postoperative period. During phacoemulsification, no attempts should be made to retrieve the dislocated nuclear fragments without proper vitrectomy. It is best advised that a vitreoretinal surgeon handles the complication. Early recognition and prompt treatment following the detachment can result in good visual recovery. PMID- 11787750 TI - Safety: what do we mean? PMID- 11787749 TI - Vitreoretinal complications of YAG laser capsulotomy. AB - Prevention is a better strategy than treating complications after they occur. Prevention approaches must focus on surgical technique, biomaterials, and IOL design aimed at reducing PCO. PMID- 11787751 TI - Agricultural work-related fatalities in Australia, 1989-1992. AB - Farm-related fatalities in Australia were studied as part of a larger study of all work-related traumatic fatalities from 1989-1992. Information concerning 373 unintentional work-related fatalities was obtained from inspection of coronial files and described. The fatality rate per 100,000 workers was four times higher for agricultural industry workers (20.6) compared to the all-industry rate during the same time frame (5.5). Males comprised 95% of all agricultural work-related deaths. Agents such as farm vehicles, mobile farm machinery (mainly tractors), and farm structures (mainly dams) were among the most common involved in the fatal incident. Being hit by moving objects, vehicle accidents, and rollovers of mobile machinery (mainly tractors) were among the most common mechanisms of fatal injury on farms. Transport for work purposes, working with animals, working with crops, and maintenance were the most common activities being undertaken. The information obtained from this study is being used to develop health and safety risk profiles for agricultural industries, and these profiles are being used in turn to develop guidance material for farmers, on-farm checklists, and other tools to help farmers manage their occupational health and safety risk. PMID- 11787752 TI - Non-work-related farm fatalities in Australia, 1989-1992. AB - This study aims to examine farm fatalities, between 1989-1992 in Australia, of individuals not working at the time of the incident. Non-work-related farm fatalities in Australia were studied as part of a larger study of all work related traumatic fatalities from 1989-1992. Information on 214 unintentional non work-related farm fatalities was obtained from inspection of coronial files. The information was examined according to type of bystander (bystander to work or bystander to farm equipment) and other farm deaths. Agents such as dams, tractors, utilities, and cars were among the most common causes of death for bystanders involved in fatal incidents. Fire and smoke, creeks or rivers, and cars were the most common agents for other farm deaths. Drowning, vehicle accidents, and being hit by moving objects were among the most common mechanisms of fatal injury for non-work-related farm deaths. The information gained from this study has been used to develop the Child Safety on Farms Strategy for Farmsafe Australia and Farmsafe Australia's Farm Machinery Safety Strategy. PMID- 11787753 TI - Agricultural work activities reported for children and youth on 498 North American farms. AB - Children are at high risk for agricultural injury, yet there is little documentation about the range of farm work that children perform or the ages at which children experience these work exposures. The purpose of this study was to identify the scope of agricultural jobs performed by farm children and to describe variations in work involvement within demographic subgroups. A descriptive analysis was conducted of baseline data collected by telephone interview during a multi-site randomized controlled trial. The study population consisted of 1,138 children from 498 North American farms. A total of 2,389 jobs were reported for the 1,138 children. The leading categories of work were animal care, crop management, and tractor with implement operation. Regional differences were observed, consistent with variations in commodities. Substantial proportions of children were assigned to farm work even in the youngest age group of 7-9 years. Males were differentially assigned to tractor with implement operations, while females were more often assigned to animal care. This study provides one of the first systematic accounts of farm work performed by North American children. This analysis of work exposures provides information from which known prevention priorities can be reinforced and new opportunities for prevention identified. PMID- 11787754 TI - Evaluation of a microwave and infrared human-presence sensing system for agricultural equipment. AB - The potential use of electronic safety sensors to protect operators from agricultural equipment with rotating hazards has been identified and discussed as a possible means to prevent traumatic entanglement injury. A multi-sensor human presence sensing system to protect persons approaching a rotating PTO shaft powering a stationary implement was developed using commercially available, passive infrared and microwave sensors. A control and data acquisition system was designed and constructed to evaluate sensor performance and response. The sensor system performed well during 822 warm weather test passes in which a person approached the potentially hazardous area near the drawbar and PTO/IID located between an IH 986 test tractor and a self-unloading forage wagon. During the 822 test passes, there were no false alarms and no misses. Operators approached the hazard space walking from 92 to 227 cm/second. During tests, the sensing system yielded warning times generally between 0.5 and 1.0 seconds, providing an estimate of the time available to accomplish machine shutdown or operator warnings. Additional cold weather tests caused the control and data acquisition hardware to function erratically. This work suggests that multi-sensor human detection systems have the potential to reduce false alarms through redundancy when more than one sensor is required to detect a person before the system signals a "detect" condition. However, the use of multiple, redundant sensors also increases the potential for a "miss." Further work is needed to determine whether these types of sensor can yield timely enough information to prevent injury via mechanical shutdown or operator warnings. PMID- 11787755 TI - Surveillance of the gastrointestinal mucosa by sensory neurons. AB - A dense network of extrinsic and intrinsic sensory neurons supplies the gastrointestinal tract. Intrinsic sensory neurons provide the enteric nervous system with the kind of information that this brain of the gut requires for its autonomic control of digestion, whereas extrinsic afferents notify the brain about processes that are relevant to energy and fluid homeostasis and the sensation of discomfort and pain. The sensory repertoire of afferent neurons is extended by their responsiveness to mediators released from enteroendocrine and immune cells, which act like "taste buds" of the gut and serve as interface between the gastrointestinal lumen and the sensory nerve terminals in the lamina propria of the mucosa. Functional bowel disorders such as non-ulcer dyspepsia and irritable bowel syndrome are characterized by abdominal discomfort or pain in the absence of an identifiable organic cause. It is hypothesized with good reason that infection, inflammation or trauma causes sensory pathways to undergo profound phenotypic and functional alterations that outlast the acute insult. The pertinent changes involve an exaggerated sensitivity of the peripheral afferent nerve fibres as well as a distorted processing and representation of the incoming information in the brain. This concept identifies a number of receptors and ion channels that are selectively expressed by primary afferent neurons as important molecular targets at which to aim novel therapies for functional bowel disorders. PMID- 11787756 TI - Central and peripheral neural control of pancreatic exocrine secretion. AB - Efferent vagal impulses act on the exocrine pancreas via pancreatic ganglia, where the impulses are modulated and modified, and terminate via postganglionic fibers at the acinar cells. Acinar muscarinic receptors of the subtype M1 play an important role for the mediation of the stimulatory vagal influences on pancreatic exocrine secretion. In dogs, a potentiative interaction exists between the two most important mediators of the pancreatic exocrine response to intraduodenal stimuli, efferent vagal impulses and CCK. In contrast to humans and rats, in which all action of CCK on pancreatic enzyme output is vagally mediated, CCK acts in dogs in part as a classical humoral factor independent of the cholinergic system. Although several peptides found in pancreatic nerve cell bodies or fibers can stimulate or inhibit pancreatic exocrine secretion, their physiological importance in the neural control of the exocrine pancreas needs to be further evaluated. PMID- 11787757 TI - Role of histamine H3 receptors in the regulation of gastric functions. AB - The role of central and peripheral histamine H3 receptors in the regulation of gastric acid secretion and gastric mucosal integrity is reviewed. The activation of H3 receptors by peripheral administration of the selective agonist (R)alpha methylhistamine reduced acid secretion in cats, dogs, rats and rabbits, while increasing it in mice. The antisecretory effects were observed against indirect stimuli that act on vagal pathways or on enterochromaffin-like (ECL) cells, such as 2-deoxy-D-glucose, food or pentagastrin, but not against histamine or dimaprit. Inhibitory effects on acid production were observed in rats after central administration of histamine or of H3 receptor agonists. In the conscious rat intragastric administration of (R)alpha-methylhistamine caused gastroprotective effects against the damage induced by absolute ethanol, HCl, aspirin and stress. The mechanism involved seems to be related to the increased mucus production, via nitric oxide-independent mechanisms. Gastroprotective effects against ethanol were also observed after central administration of histamine or its metabolite N(alpha)-methylhistamine, suggesting that brain receptors participate the histamine-mediated effects on gastric functions. PMID- 11787758 TI - Neural aspects of prostaglandin involvement in gastric mucosal defense. AB - In rats, central vagal stimulation by thyrotropin-releasing hormone protects against ethanol-induced gastric damage by muscarinic release of prostaglandins. In contrast, gastroprotection following capsaicin-induced stimulation of afferent neurons is prostaglandin-independent. Capsaicin-evoked protection is abolished by blockade of calcitonin gene-related peptide (CGRP) receptors and inhibition of nitric oxide (NO) synthase. Various peptides including gastrin 17, cholecystokinin octapeptide, thyrotropin-releasing hormone, bombesin, corticotropin-releasing factor, epidermal growth factor, peptide YY, neurokinin A analogs and intragastric peptone exert gastroprotection that is abolished by afferent nerve denervation, blockade of CGRP receptors and inhibition of NO synthase. Indomethacin attenuates the protection of some peptides but has no effect with others. The hyperemic response to peptides is mediated by the afferent nerve/CGRP/NO system without contribution of prostaglandins. Furthermore, it was shown that NKA analogs exert afferent nerve-, CGRP- and NO dependent gastroprotection in the face of substantial reduction of gastric mucosal blood flow indicating that gastroprotection is not necessarily mediated by mucosal hyperemia. In the rat stomach with functioning afferent nerves neither selective inhibition of cyclooxygenase (COX)-1 nor COX-2 is ulcerogenic and only simultaneous inhibition of both COX isoenzymes induees mucosal lesions. In the face of pending injury such as intragastric acid a COX-1 inhibitor evokes dose dependent damage whereas COX-2 inhibitors are not injurious as long as the function of afferent nerves is not impaired. After afferent nerve denervation, however, COX-2 inhibitors or dexamethasone which suppresses the acid-induced up regulation of COX-2 are highly ulcerogenic. In conclusion, release of prostaglandins following nerve stimulation can mediate protective effects under certain conditions but is not a prerequisite for neurally mediated mucosal defense. Prostaglandins are of particular importance for the maintenance of gastric mucosal integrity when neuronal defense mechanisms are impaired. PMID- 11787759 TI - Sensory nerves and calcitonin gene related peptide in the effect of ischemic preconditioning on acute and chronic gastric lesions induced by ischemia reperfusion. AB - Ischemic preconditioning is considered as the most powerful gastroprotective intervention against mucosal lesions and ulcerations but the mechanism of this phenomenon has been little examined. In this study we tested the effects of inactivation of sensory nerves in new rat model combining acute gastric erosions with subsequent ulcers induced by ischemia-reperfusion (I/R). I/R lesions were produced in rats by clamping the celiac artery for 0.5 h followed by 3 h of reperfusion in rats with intact or inactivated sensory nerves by pretreatment with capsaicin for two weeks before the I/R. The animals were killed at 0 and 3 h and 3 days after I/R and the area of gastric lesions was determined planimetrically, the gastric blood flow (GBF) by H2-gas clearance technique and the plasma levels of gastrin by RIA. Gastric mucosal content of calcitonin gene related peptide (CGRP) was assessed by RIA. Following I/R, gastric erosive lesions occurred after 3 h and these erosive lesions then progressed into gastric ulcers within 3 days in all rats. Sensory-inactivation with capsaicin caused several fold increase in the area of early (at 3 h) acute lesions and later (at 3 d) gastric ulcers induced by I/R. This enhancement of acute and then chronic gastric lesions was accompanied by a significant fall in GBF, an elevation of plasma gastrin and a decrease in mucosal expression of CGRP. Ischemic preconditioning markedly reduced acute lesions and chronic ulcerations induced by I/R and attenuated the changes in plasma gastrin and mucosal CGRP contents but these effects were significantly more pronounced in rats with intact sensory nerves but less in capsaicin-inactivated animals. We conclude that: 1) The I/R resulted in the formation of early acute gastric lesions followed 3 days later by chronic gastric ulcers and this gastric injury was accompanied by an impairment of gastric microcirculation, hypergastrinemia and suppression the gastric mucosal CGRP; 2) Gastric ischemic-preconditioning significantly attenuated both acute mucosal damage and chronic ulcers induced by I/R and this was accompanied by a rise in gastric blood flow; 3) The inactivation of sensory nerves with capsaicin enhanced the formation of I/R-induced acute and chronic gastric lesions and strongly attenuated the gastroprotection afforded by I/R possibly due to the decline in mucosal blood flow and the fall in expression of integrity peptides such as CGRP and 4) The excessive release of gastrin may limit the extent of mucosal lesions observed during progression of gastric erosions into ulcers induced by I/R. PMID- 11787761 TI - The effect of transcutaneous nerve stimulation (TENS) on gastric electrical activity. AB - TENS became widely accepted method of treatment pain syndromes in clinical practice. Lately has been shown that its affects also gastrointestinal tract by releasing NANC neurotransmitter VIP. The aim of this study was to evaluate the effects of TENS on gastric myoelectric activities measured by electrogastrography (EGG). Eighteen healthy men (mean age 23 +/- 1.7) were included in the study. Healthy volunteers were divided on 3 groups each 6 persons: with normogastria occurring at 94.5 +/- 7% of recording time--group A, with predominant bradygastria (36.6 +/- 14%)--group B and with tachygastria (33 +/- 14%)--group C. In fasted condition EGG (Synectics, Sweden) was recorded with skin electrodes. TENS 15 min was performed with use of Sinus 5 stimulator (6 Hz, 0.1 ms duration, intensities 10-20 mA, Zimmer, Germany). Stimulating electrodes were placed on non dominant hand. RESULTS: None of the subjects during TENS reported any side effects or symptoms, during the all studies. In group A in the fasting recordings, after TENS, an decrease of the normal values in the range 2-4 cpm down to 78.5 +/- 21% of recording time (p = 0.03) occurred. The dominant frequency in the bradygastric region increased up to 17.7 +/- 7% of the total recording. In group B TENS decreased bradygastria level from 36.6 +/- 14% to 20.6 +/- 15% (p = 0.02). TENS did not significantly affect tachygastria in group C. Amplitude of the EGG signal after TENS in group B and C increased by 40 and 150% respectively (p < 0.05). Significant decrease of the amplitude was observed in group A (13%). We conclude that TENS by activating centrally mediated somato visceral reflexes affects gastric electrical activity. Our results suggest that TENS may be useful in treatment of the gastric dysrhythmia. PMID- 11787760 TI - Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia reperfusion induced gastric lesions. AB - Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGR(8-37) (100 microg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1-20 microg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 microg/kg and 6 microg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 microg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 microg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP(8-37). The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but not those of leptin while capsaicin denervation counteracted leptin-induced protection and rise in the GBF but attenuated significantly those of CCK. We conclude that: 1) central leptin exerts a potent gastroprotective activity against I/R-induced gastric erosions that progress into deeper gastric lesions and this protection depends upon vagal activity and sensory nerves and involves hyperemia probably mediated by NO and 2) leptin mimics the gastroprotective effect of CCK and may be implicated in the protective and hyperemic actions of this peptide against mucosal damage evoked by I/R. PMID- 11787762 TI - Central and peripheral neural aspects of gastroprotective and ulcer healing effects of lipopolysaccharides. AB - Lipopolysaccharides (LPS) are major components of the outer membrane of gram negative bacteria playing a central role as potent endotoxins in the pathogenesis of endotoxic shock. Although large amounts of endotoxin may produce hemorrhagic lesions in the stomach, the possible gastroprotective effect of central or peripheral LPS against the acute gastric lesions has not been extensively studied. The aim of the present study was to compare the effect of intracerebroventricular (i.c.v.) and parenteral (i.p.) injection of LPS against gastric lesions induced by 100% ethanol. Male Wistar rats were treated either with a) vehicle (control); b) E-coli-LPS in various concentrations (1-10 microg/kg i.c.v or 0.1-40 mg/kg i.p.) followed 30 min later by 100% ethanol. The effects of pretreatment with nonselective inhibitor of nitric oxide synthase (L NAME, 20 mg/kg i.g.) or selective inhibitor of inducible nitric oxide synthase, L NIL (30 mg/kg i.g.) on the gastroprotection induced by LPS was investigated. One hour after ethanol application, the gastric blood flow (GBF) and the area of gastric lesions were determined. In addition, the mucosal expression of iNOS, cNOS and leptin was assessed using RT-PCR. LPS applied i.c.v. or i.p. dose dependently reduced gastric lesions induced by ethanol and this effect was similar to that observed after the administration of NO donor (SNAP). LPS-induced protection was significantly abolished by L-NAME and significantly attenuated by the selective inhibitor of iNOS (L-NIL). The expression of cNOS was detected in vehicle treated gastric mucosa and did not change after LPS administration. iNOS was not detectable in intact mucosa but its expression dose-dependently increased after the LPS administration. The i.c.v. administration of LPS did not upregulate further the iNOS expression, and dose-dependently inhibited the leptin mRNA expression in gastric mucosa. We conclude that LPS applied centrally or peripherally protects gastric mucosa against ethanol-induced damage through an increase in gastric microcirculation mediated by NO due to overexpression of iNOS. Transcriptional downregulation of leptin in gastric mucosa is probably due to the increased leptin release induced by the intracerebroventricular application lipopolysaccharide. PMID- 11787763 TI - Effect of central and peripheral actions of histamine and its metabolite N-alpha methyl histamine on gastric secretion and acute gastric lesions. AB - N alpha-methylhistamine (N alpha-MH) is one of unusual metabolite of histamine that was found in Helicobacter pylori-infected stomach and is believed to interact with specific histamine H1, H2 and H3-receptors to stimulate gastric acid secretion and gastrin release from isolated G-cells but the effects of N alpha-MH on gastric mucosal integrity have been little studied. This study was designed; 1) to compare the effect of intraperitoneal (i.p.), intracerebroventricular (i.c.v.) and gastric topical (intragastric i.g.) application of exogenous N alpha-MH with that of standard histamine on gastric secretion in rats equipped with gastric fistula (series A) and 2) to compare the effect of i.c.v. administration of histamine and N alpha-MH with that of peripheral (i.p. and i.g.) application of these amines on gastric lesions induced by 100% ethanol (series B) in rats with or without capsaicin-induced deactivation of sensory nerves. The area of gastric lesions was determined planimetrically, gastric blood flow (GBF) was assessed by H2-gas clearance method and venous blood was collected for determination of plasma gastrin levels by RIA. N alpha-MH and histamine (0.1-10 mg/kg i.p. or i.g.) dose-dependently increased gastric acid output (series A); whereas i.c.v. administration of histamine or N alpha-MH inhibited dose-dependently this secretion; the dose attenuating gastric acid output by 50% (ED50) being 4 and 6 microg/kg i.c.v. Both, N alpha-MH and histamine (2 mg/kg i.p. and i.g.) attenuated significantly the area of gastric lesions induced by 100% ethanol (series B) while producing significant rise in the GBF and plasma immunoreactive gastrin increments. Central application of N alpha-MH and histamine (0.01-5 microg/kg i.c.v.) inhibited ethanol-induced gastric damage whereas higher doses ranging from 10-100 microg/kg of histamine and N alpha-MH were significantly less effective. Capsaicin-induced deactivation of sensory nerves by itself augmented significantly ethanol damage and attenuated significantly the protective and hyperemic effects of histamine and its methylated analog applied i.p. but failed to affect significantly those caused by i.c.v. administration of these amines. We concluded that: 1) central histamine and N alpha-MH inhibits gastric acid secretion and exhibits gastroprotective activity against ethanol in similar manner to that afforded by parenteral and topical histamine and N-alphaMH, 2) central N-alphaMH- and histamine-induced protection involve the enhancement in gastric microcirculation unrelated to neuropeptides released from capsaicin-sensitive afferent nerves, and 3) the major difference between central and peripheral histamine and its methylated analog is the influence on gastric acid secretion which does not appear to play any major role in gastroprotective activity of these agents. PMID- 11787764 TI - Pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs. AB - We examined the local effect of several drugs against secretagogue-stimulated acid secretion in dogs. Test drugs were applied to denervated gastric pouches in conscious dogs either for 5 to 30 min beginning 1 hr after or for 30 min before intravenous infusion of gastric secretagogues (histamine, pentagastrin, or carbachol). The antisecretory effect of test drugs delivered by an intravenous or oral route was also examined. Local application of acid pump inhibitors (omeprazole, leminoprazole) for 30 min beginning 1 hr after histamine infusion significantly inhibited gastric acid secretion. The effect of leminoprazole persisted for more than 8 hr after a 30 min application. A mast cell stabilizer (FPL 52694) applied to pouches for 15 to 30 min also potently inhibited histamine stimulated gastric acid secretion in a time-dependent manner. The duration of the antisecretory effect of such drugs after a 30 min application was greater than 4 hr. Locally applied leminoprazole and FPL 52694 for 30 min also significantly inhibited pentagastrin- and carbachol-stimulated gastric acid secretion. Although intravenous omeprazole and leminoprazole exerted a potent antisecretory effect on histamine-induced acid secretion FPL 52694 had little or no antisecretory effect following intravenous or oral administration. 16,16-dimethyl prostagladin E2 also locally inhibited histamine-stimulated acid secretion. Acid stable local anesthetics (tetracaine, ethyl-4-aminobenzoate), histamine H2-receptor blockers (cimetidine, ranitidine, and famotidine), and a muscarinic M1-receptor antagonist (pirenzepine) did not exhibit local antisecretory effects. Such results strongly suggest that the apical membrane of parietal cells possesses a pharmcologically sensitive portion similar to the basolateral membrane, which usually mediates gastric acid secretion. The apical membrane represents an intriguing target for new antisecretory drugs, as well as a new medium for further elucidating the functional features of parietal cells. PMID- 11787765 TI - Cerebral and gastric histamine system is altered after portocaval shunt. AB - Biochemical parameters of the histamine (HA) system were examined in both rat brain and stomach, after portocaval anastomosis (PCA). These tissues become rich in histamine after PCA. Immunocytochemistry was used for brain histamine localisation. In addition to increased HA concentrations, monoamine oxidase B activity increased in both tissues. In hypothalamus HA was 15 fold; in cerebral cortex and in stomach mucosa 2.8 and 2.5 fold of the corresponding controls, respectively. MAO B activity was increased by approximately 50% in brain and 100% in stomach. A significant, uneven increase in tele-methylhistamine concentration was only found in the brain. In stomach mucosa higher histidine decarboxylase activity was found. PCA and sham rats treated with an irreversible inhibitor of MAO B, FA-73, 0.5 mg/kg i.p., showed 24 h later greatly reduced MAO activity and doubled t-MeHA concentration in brain structures. The treatment had no effect on gastric mucosal t-MeHA concentration and urinary excretion of the t-MeHA metabolite, N-tele-methylimidazoleacetic acid. The HA rise in the stomach of PCA rats is associated with proliferation of histamine producing and storing cells (ECL cells) as demonstrated by others. However, in the brain we saw no indication for increased number of relevant cells either mast cells or neurons and our immunocytochemical findings suggest that in PCA rat brain, histamine deposits are located exclusively in neurons. The data indicate that the adaptative mechanisms to excessive histamine formation are tissue specific. PMID- 11787766 TI - Central nervous stimuli increase duodenal bicarbonate secretion by release of mucosal melatonin. AB - A number of common diseases in humans, including gastroduodenal ulcer and irritable bowel syndrome, show circadian rhythms in pain and discomfort. The neurohormone melatonin is released from enterochromaffin cells in the intestinal mucosa and from the pineal gland but its role in gastrointestinal function is largely unknown. We have studied the involvement of melatonin in stimulation of the mucosa-protective alkaline secretion by the duodenal mucosa. A 12-mm segment of proximal duodenum with an intact blood supply was cannulated in situ in anesthetized rats and duodenal HCO3- secretion titrated by pH-stat. Duodenal close intra-arterial infusion of melatonin or the full agonist 2-iodo-N-butanoyl- 5-methoxytryptamine significantly increased the secretion and pretreatment with the melatonin (predominantly MT2-receptor specific) antagonist luzindole almost abolished the response. Intracerebroventricular (i.c.v.) infusion of the alpha1 adrenoceptor agonist phenylephrine (12.2 micromol kg(-1) x h(-1)) caused an up to fivefold increased in the alkaline secretion and the melatonin antagonist luzindole or cutting all peri-carotid nerves abolished the duodenal secretory response to i.c.v. phenylephrine. Peripheral melatonin thus stimulates duodenal mucosal HCO3- secretion and endogenous melatonin, very likely released from mucosal enterochromaffin cells, is involved in mediating neural stimulation of the secretion. PMID- 11787768 TI - Effects of continuous microchip (MC) vagal neuromodulation on gastrointestinal function in rats. AB - Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250-350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5-30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 +/- 2.5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid--intragastrically) almost doubled amount of bursts to 12 +/- 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 +/- 4.8 vs control 35.5 +/- 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 +/- 9.08 vs control 23.56 +/ 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 +/- 9.3 vs control 98.5 +/- 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 +/- 0.8 vs 1.17 +/- 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 +/- 0.35 vs 0.68 +/- 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 +/- 0.14 vs 0.14 +/- 0.12 mmol/30 min, p < 0.05) but MAO did not change in MC rats (0.37 +/- 0.25 vs 0.42 +/- 0.28 mmol/30 min, p 0.05). Gastric emptying of isotonic solution increased by 10% (90.46 +/- 5.34 vs 80.39 +/- 9.95) percent of marker passing to duodenum/5 min, p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight. PMID- 11787767 TI - Effect of sensory nerves and CGRP on the development of caerulein-induced pancreatitis and pancreatic recovery. AB - The function of primary sensory neurons is to receive and transmit information from external environment and these neurons are able to release neuromediators from the activated peripheral endings. The aim of this study was to determine the influence of sensory nerves and administration of their mediator--calcitonin gene related peptide (CGRP) on the course of acute pancreatitis (AP). Ablation of sensory nerves was performed by neurotoxic dose of capsaicin (100 mg/kg). Single or repeated episodes of AP were induced by caerulein infusion (10 microg/kg/h for 5 h). Five repeated AP were performed once a week. Capsaicin at the dose which stimulates sensory nerves (0.5 mg/kg/dose) or CGRP (10 microg/kg/dose) was administrated before and during or after single induction of AP, as well as, after each induction of repeated AP. Rats were killed at the time 0, 3 or 9 h after single induction of AP or two weeks after last induction of repeated AP. Ablation of sensory nerves aggravated pancreatic damage in caerulein-induced AP. Treatment with stimulatory doses of capsaicin or CGRP before and during single induction of AP attenuated the pancreatic damage in morphological examination. This effect was also manifested by partial reversion of AP evoked drop in DNA synthesis and pancreatic blood flow (PBF). Administration of CGRP after single AP induction aggravated histologically manifested pancreatic damage. The further decrease in PBF and DNA synthesis was also observed. Animals with five episodes of AP showed almost full pancreatic recovery two weeks after last induction of AP concerning all parameters tested. In stimulatory doses of capsaicin treated rats, we observed the decrease in pancreatic amylase and fecal chymotrypsin activity, as well as, the drop in DNA synthesis. Similar but less pronounced effects were observed after treatment with CGRP. We conclude that effect of sensory nerves and CGRP on AP is two-phase and time dependent. Stimulation of sensory nerves or the administration of CGRP during development of AP exhibits protective effects against pancreatic damage induced by caerulein overstimulation. After induction of AP, persistent activity of sensory nerves and presence of CGRP aggravate pancreatic damage and lead to functional insufficiency typical for chronic pancreatitis. PMID- 11787769 TI - Thyroid hormone regulation of apoptotic tissue remodeling during anuran metamorphosis. AB - Anuran metamorphosis involves systematic transformations of individual organs in a thyroid hormone (TH)-dependent manner. Morphological and cellular studies have shown that the removal of larval organs/tissues such the tail and the tadpole intestinal epithelium is through programmed cell death or apoptosis. Recent molecular investigations suggest that TH regulates metamorphosis by regulating target gene expression through thyroid hormone receptors (TRs), which are DNA binding transcription factors. Cloning and characterization of TH response genes show that diverse groups of early response genes are induced by TH. The products of these TH response genes are believed to directly or indirectly affect the expression and/or functions of cell death genes, which are conserved at both sequence and function levels in different animal species. A major challenge for future research lies at determining the signaling pathways leading to the activation of apoptotic processes and whether different death genes are involved in the regulation of apoptosis in different tissues/organs to effect tissue specific transformations. PMID- 11787770 TI - Molecular signal transduction in vascular cell apoptosis. AB - Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes. PMID- 11787771 TI - Existence of homologous sequences corresponding to cDNA of the ver gene in diverse higher plant species. AB - The presence of DNA homologues corresponding to verc203 (vernalization-related cDNA clone) was investigated by molecular hybridization techniques. The genes were detected in 16 plant species that cover 12 subclasses of the Takhtajan system of angiosperms classification including diverse model species. The results of Southern blot analysis showed a low copy number of this gene existed in rice, wheat, barley and Arabidopsis. The hybridization result of PCR products demonstrated the conservation of the gene corresponding to ver203 in diverse plants. The phylogenetic tree of the ver203 gene in tested plants was supported by evolution relationship of species. The ver203 gene expressed in a vernalized plumule winter wheat, instead of the root. And the endosperm before the treatment was essential for the ver203 expression during vernalization in wheat. In Arabidopsis thaliana, the pattern of expression showed that the gene corresponding to ver203 was expressed at low temperature for 14 days. Gibberellin (GA3) may accelerate the expression of ver203 gene in Arabidopsis exposed to low temperature. However, it could not replace vernalization treatment to initiate the gene expression. PMID- 11787772 TI - Auxin distribution and transport during embryogenesis and seed germination of Arabidopsis. AB - Auxin distribution during embryogenesis and seed germination were studied with transgenic Arabidopsis plants expressing GUS gene driven by a synthetic DR5 promoter, an auxin responsive promoter. The results showed that GUS activity is higher in ends of hypophysis and cotyledon primordia of heart-, torpedo- and cotyledon-stage embryos, leaf tip area, lateral root primordia, root apex and cotyledon of young seedlings. And GUS accumulated in root apex of the seedlings grown on auxin transport inhibitor containing media. All these suggested that above-mentioned part of the organs and tissues have a higher level of auxin, and auxin polar transport inhibitor could cause the accumulation of auxin in root apex. And auxin transport inhibitor also resulted in aberration of Arabidopsis leaf pattern formation, root gravitropism and elongation. PMID- 11787773 TI - Regeneration of plants from callus tissues of hairy roots induced by Agrobacterium rhizogenes on Alhagi pseudoalhagi. AB - The legume forage Alhagi pseudoalhagi was transformed by the Agrobacterium rhizogenes strain A4 using cotyledon and hypocotyl segments as infection materials. Regenerated plants were achieved from sterile calli derived from hairy roots, which occurred at or near the infection sites. The regenerated plants from hairy root were characterized by normal leaf morphology and stem growth but a shallow and more extensive root system than normal plants. Opine synthesis, PCR and Southern blot confirmed that T-DNA had been integrated into the A. pseudoalhagi genome. Acetosyringone (AS) was found to be vital for successful transformation of A. pseudoalhagi. PMID- 11787774 TI - Overexpression of a novel gene, Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor. AB - MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutant (mcm10-1) of budding yeast shows a growth arrest at 37 degrees C. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37 degrees C. Interestingly, this mcm10-1 suppressor undergoes cell cycle arrest at 14 degrees C. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cms1 (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of transformation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14 degrees C, indicating that overexpression of Cms1 can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control. PMID- 11787775 TI - Function of GATA transcription factors in hydroxyurea-induced HEL cells. AB - HEL cells, a human erythroleukemia cell line, mainly express the fetal (gamma) globin gene and trace amount of the embryonic (epsilon) globin gene, but not adult (beta) globin gene. Here we show that hydroxyurea (HU) can induce HEL cells to express adult (beta) globin gene and lead these cells to terminal differentiation. Results showed in Gel mobility shift assays that GATA factors could specifically bind to the regulatory elements of human beta-globin gene, including the proximal regulatory element (the beta-promoter) and the distal regulatory elements (the DNase I hypersensitive sites in the LCR, HS2-HS4 core sequences). However, the DNA binding patterns of GATA factors were quite different between HU-induced and uninduced HEL cells. Western-blot analysis of nuclear extracts from both the uninduced and HU-induced HEL cells revealed that the level of GATA-2 transcription factor decreased, whereas the level of GATA-1 transcription factor increased following the time of hydroxyurea induction. Furthermore, using RT-PCR analysis the expression of human beta-globin gene in HU induced HEL cells could be blocked again when HEL cells were incubated in the presence of antisense oligonucleotides for hGATA-1, suggesting that the upregulation of hGATA-1 transcription factor might be critical for the expression of human beta-globin gene in HU-induced HEL cells. PMID- 11787776 TI - Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells. AB - In order to study the mechanism of the effect of heparin on apoptosis in carcinoma cells, the nasopharyngeal carcinoma cell line CNE2 was used to identify the effect of heparin on apoptosis associated with the expression of c-myc, bax, bcl-2 proteins by use of Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), agarose gel electrophoresis, and flow cytometry, as well as Western blot analysis. The results showed that heparin induced apoptosis of CNE2 cells including the morphologic changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the "ladder pattern" revealed by agarose gel electrophoresis of DNA in a concentration-dependent manner. The number of TUNEL-positive cells was dramatically increased to 33.6+/-1.2% from 2.8+/-0.3% by treatment with heparin in different concentrations (10 to approximately 40 kU/L). The apoptotic index was increased to 32.5% from 3.5% by detecting SubG1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes. PMID- 11787777 TI - Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat. AB - The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state. PMID- 11787778 TI - Expression of estrogen receptor (ER) -alpha and -beta transcripts in the neonatal and adult rat cerebral cortex, cerebellum, and olfactory bulb. AB - In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen. PMID- 11787779 TI - Sheep brain pool experiment 'will not yield valid results'. PMID- 11787780 TI - Veterinarian to be struck off for failing to store drugs securely. PMID- 11787781 TI - Environmental contamination and detection of Salmonella enterica serovar enteritidis in laying flocks. AB - Faecal, dust and other environmental samples were collected from the floors, droppings belts, egg-collection systems and other areas of 14 cage-layer flocks, 10 barn egg production flocks and seven free-range flocks, and cultured for Salmonella species. The distribution of the organism varied with its prevalence and with the vaccination status of the birds. No one sample type was found to be suitable for identifying all contaminated houses. Salmonella was also frequently found on egg-packing equipment and in samples from rodents and wild birds. PMID- 11787782 TI - Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of dogs infested experimentally with Ctenocephalides canis and Ctenocephalides felis felis. AB - Twenty-four beagles were randomly allocated into four groups of six and housed in separate cages. Each dog was infested with 25 Ctenocephalides canis and 25 Ctenocephalides felis felis and two days later (day 0) the dogs in groups 1, 2 and 3 received a spot-on application of selamectin (6 mg/kg), imidacloprid (10 mg/kg), or fipronil (6-7 mg/kg), respectively, while the dogs in group 4 were not treated. The dogs were combed 48 hours later, the fleas were removed, counted and their species were determined. All the dogs were reinfested with the same number of the two species of fleas on days 7, 14, 21, 28 and 35, and the efficacy of the treatments was calculated 48 hours after each infestation. The mean numbers of fleas on the control dogs were 19.8 C. canis and 14.7 C. felis felis. The three treatments were effective for the full 35 days of the trial; over the first 28 days, the efficacy of selamectin ranged from 81 to 100 and 92 to 99 per cent against C. felis felis and C canis, respectively, the efficacy of imidacloprid ranged from 98 to 100 per cent and the efficacy of fipronil was 100 per cent against both species. There were no significant differences between the three treatments. PMID- 11787783 TI - In vitro microelectrode study of the electrical properties of smooth muscle in equine ileum. AB - Intracellular microelectrode recordings were made from smooth muscle cells in cross-sectional preparations of equine ileum, superfused in vitro. Membrane potential oscillations and spike potentials were recorded in all preparations, but recordings were made more readily from cells in the longitudinal muscle layer than from cells in the circular layer. The mean (se) resting membrane potential (RMP) of smooth muscle cells in the longitudinal muscle layer was -51.9 (1.2) mV, and the membrane potential oscillations in this layer had a mean amplitude of 4.8 (0.4) mV, a frequency of 9.0 (0.1) cycles per minute and a duration of 5.8 (0.2) seconds. The membrane potential oscillations were preserved in the presence of tetrodotoxin. A waxing and waning pattern of membrane potential oscillation activity was observed. Nifedipine abolished the spiking contractile activity of the smooth muscle, did not abolish the membrane potential oscillations but did alter their temporal characteristics. PMID- 11787784 TI - Ovine placentitis and abortion associated with a verotoxigenic strain of Escherichia coli. PMID- 11787785 TI - Diagnosis of Mycobacterium bovis infection in a mare. PMID- 11787786 TI - Caprine offspring born from fresh and frozen-thawed in vitro-produced embryos. PMID- 11787787 TI - First report of Babesia bovis in Spain. PMID- 11787788 TI - Anthelmintic-resistant Cooperia species in cattle. PMID- 11787789 TI - Aleutian disease, mink and otters. PMID- 11787790 TI - Ethical decision-making in veterinary practice. PMID- 11787791 TI - Veterinary nursing. PMID- 11787792 TI - Effects of adsorbent properties on zone spreading in expanded bed chromatography. AB - The mixing performance as well as the adsorption performance in expanded bed chromatography (EBC) was investigated by using various types of adsorption media (average particle size = 100-700 microm, density = 1100-1700 kg/m3, base matrix = hydroxyapatite, styrene-divinylbenzene, cross-linked agarose). The scale down study with 0.8 cm diameter columns was also attempted. Pulse response curves were measured with vitamin B12 as a tracer [Residence time distribution RTD experiments], and the HETP (height equivalent to a theoretical plate or plate height) values were calculated from the peak variance and the peak retention time. The HETP values for different types of packing media tested showed very similar values (0.5-1.0 cm), which did not depend on the flow-rate or the column diameter (0.8-2.6 cm). Dynamic binding capacity (DBC) values of lactic acid on a Dowex anion-exchange resin were determined from breakthrough curve (BTC) measurements for both EBC and fixed bed chromatography (FBC). The DBC values for EBC were similar to those for FBC. When the liquid feed contained insoluble particles (yeast cells) the degree of mixing increased. However, the contribution of the mixing to the total spreading of BTCs for EBC was usually small so that this increase in the mixing did not affect the adsorption performance or the DBC values significantly. PMID- 11787793 TI - Design and assembly of solid-phases for the effective recovery of nanoparticulate bioproducts in fluidised bed contactors. AB - Practical recovery of nanoparticulate bioproducts from suspension feedstocks has been studied in batch, fixed bed and fluidised bed adsorptive contactors. The performance of five discrete configurations of adsorbent solid phase has been critically evaluated in the anion exchange recovery of mg quantities of BSA nanoparticles. These have served as surrogate size mimics of less easily sourced viral and plasmid gene therapy vectors, characterised by high value and a shortage of supply in quantities sufficient for research and development. Performance parameters of binding capacity, efficacy of washing, desorption efficiency and total cycle time were strongly influenced by the external and internal topographies of solid phases, together with the localised concentrations of interacting chemical ligands which modulate adsorption. In respect of a full operational recovery cycle, porous adsorbents developed for refined chromatographic fractionation of macromolecules, appear less suited overall than solid, nonporous particles, or solid particles coated with a shallow pellicle of active adsorbent material. Such findings have been confirmed in a detailed demonstration of the recovery of plasmid DNA (7.8 Kb) from chemical lysates of Escherichia coli. PMID- 11787794 TI - Buoyancy-induced mixing during wash and elution steps in expanded bed adsorption. AB - Buoyancy-induced mixing occurs during expanded bed adsorption processes when the feed stream entering the bottom of the system has a lower density than that of the fluid above it. In the absence of a headspace, mixing in the expanded bed can be modeled as a single, well-mixed vessel, with first-order dynamics. In the presence of a headspace, the system exhibits second-order dynamics for the densities typically encountered in protein chromatography, and can be modeled as two well-mixed vessels (the expanded bed and the headspace) arranged in series. In this paper, the mixing dynamics of the expanded bed are described and a mathematical model of the system is presented. Experimental measurements of density changes during the dilution of sucrose and salt solutions in a STREAMLINE 25 column are presented. These show excellent agreement with predictions using the model. A number of strategies for wash and elution in expanded mode, both in the presence and absence of headspace, are discussed. PMID- 11787795 TI - Design of expanded bed supports for the recovery of plasmid DNA by anion exchange adsorption. AB - In this study we detail the rational design of new chromatographic adsorbents tailored for the capture of plasmid DNA. Features present on current chromatographic supports that can significantly enhance plasmid binding capacity have been identified in packed bed chromatography experiments and blueprints for improved expanded bed adsorbents have been put forward. The characterisation and testing of small (20-40 microm) high density (>3.7 g cm(-3)) pellicular expanded bed materials functionalised with various anion exchange structures is presented. In studies with calf thymus DNA, dynamic binding capacities of 1.2 and 3.4 mg ml( 1) were recorded for prototype diethylaminoethyl-and polyethylene imine-linked adsorbents which were respectively 25 and 70 fold higher than those of equivalently derivatised commercial expanded bed materials. The prototype polyethylene imine-coupled material exhibited severe sensitivity to inter particle bridging by nucleic acid polymers, gave low DNA recoveries (<37%) and proved difficult to regenerate. In contrast, few operational difficulties were experienced with the diethylaminoethyl-linked prototype adsorbent and successful high capacity (>0.8 mg ml(-1)) capture of plasmid DNA from crude neutralised E. coli lysate was demonstrated. PMID- 11787796 TI - Isolation of bacteriocins through expanded bed adsorption using a hydrophobic interaction medium. AB - Two lactic acid bacterium bacteriocins were isolated from fermentation medium through expanded bed adsorption using a hydrophobic interaction gel. First, amylovorin L471, produced by Lactobacillus amylovorus DCE 471, was selected for the optimisation of the loading and eluting conditions. Secondly, the results of the optimisation were applied for the isolation of enterocin RZS C5, a bacteriocin produced by Enterococcusfaecium RZS C5. Optimal adsorption was obtained for a medium with concentration of 1.0 M ammonium sulphate and adjusted to pH 4.0 (94.9% for amylovorin L471 and 75.0% for enterocin RZS C5). Elution with 50% ethanol, buffered at pH 6.0, resulted in an optimal total recovery of the bacteriocin activity of 47.6 and 57.6%, respectively. The highest fold purification expressed as the increase in specific activity (AU/mg) corresponded to the highest recovery, being 140- and 1677-fold, respectively. Nevertheless, a total recovery of only 25.6% with an increase of the specific activity of 121 times was obtained after conventional isolation by ammonium sulphate precipitation. PMID- 11787797 TI - Routine manufacture of recombinant proteins using expanded bed adsorption chromatography. AB - Two different recombinant human proteins were purified directly from Pichia pastoris whole cell fermentation broth, containing 30-44% biomass (wet weight percent), by strong cation exchange expanded bed adsorption chromatography. Expanded bed adsorption chromatography provided clarification, product purification and product concentration in a single unit operation at large scale (2000-1 nominal fermentation volume). The efficiency of expanded bed adsorption chromatography resulted in a short process time, high process yield, and limited proteolytic degradation of the target proteins. The separations were operated using a 60-cm (d) column run at 14 l/min. For one protein, expanded bed adsorption chromatography resulted in an average product recovery of 113% (relative to fermentation supernatant) and a purity of 89% (n=10). For the other protein, the average product recovery was 99% (relative to fermentation supernatant) and the purity was 62.1 (n=10). Laboratory experiments showed that biomass reduced product dynamic binding capacity for protein 2. PMID- 11787798 TI - Capture of proteins from mammalian cells in pilot scale using different STREAMLINE adsorbents. AB - This presentation compares three different expanded bed matrices. STREAMLINE rProtein A, STREAMLINE SP-XL and STREAMLINE Chelating were monitored in respect to their ability to clarify the broth, to concentrate and to purify the distinct target protein. The capture of a mouse IgG1 and a recombinant prothrombin (PT) was carried out in pilot scale using a 100-l bioreactor and STREAMLINE 100 and 200 columns, respectively. The robustness of the process was also estimated monitoring the expansion behaviour and the cell and debris concentrations during the load and in the eluat. In all cases the capture of the target proteins was comparable to conventional chromatographic systems. The purification success was mainly dependent on the selectivity of the ligand used. The affinity process resulted in a highly purified product. The ion exchanger and chelating material mainly concentrated the product. In all three cases 100 l of cell broth were successfully processed in one run. The robustness of the ion exchanger process was poor, because of strong cell matrix interaction. However, for the chelating and especially for the affinity matrix a highly reproducible process was obtained. PMID- 11787799 TI - Expanded bed adsorption in the purification of monoclonal antibodies: a comparison of process alternatives. AB - Expanded bed adsorption (EBA) was examined as the initial capture/purification step in the purification of monoclonal antibodies from Chinese hamster ovary (CHO) cultures. Two process alternatives each using EBA were compared to a conventional Protein A process without EBA. One alternative used Protein A affinity EBA followed by packed-bed cation and anion-exchange steps. The other alternative used cation-exchange EBA as the capture step followed by packed-bed Protein A and anion-exchange steps. The process using Protein A EBA produced comparable purity (host cell protein, DNA, Protein A, antibody aggregate) to the conventional process. However, the Protein A EBA column showed a significant decrease in dynamic capacity with a limited number of cycles. The process using cation EBA achieved comparable levels of host cell proteins (HCP) and DNA but not antibody aggregate or leached Protein A compared to the conventional process. PMID- 11787800 TI - Minimising biomass/adsorbent interactions in expanded bed adsorption processes: a methodological design approach. AB - Expanded bed adsorption (EBA) is an integrated technology for the primary recovery of proteins from crude feedstock. Interactions between solid matter in the feed suspension and fluidised adsorbent particles influence bed stability and therefore have a significant impact on protein adsorption in expanded beds. In order to design efficient and reliable EBA processes a strategy is needed, which allows to find operating conditions, where these adverse events do not take place. In this paper a methodological approach is presented, which allows systematic characterisation and minimisation of cell/adsorbent interactions with as little experimental effort as possible. Adsorption of BSA to the anion exchanger Streamline Q XL from a suspension containing S. cerevisiae cells was chosen as a model system with a strong affinity of the biomass towards the stationary phase. Finite bath biomass adsorption experiments were developed as an initial screening method to estimate a potential interference. The adhesiveness of S. cerevisiae to the anion exchanger could be reduced significantly by increasing the conductivity of the feedstock. A biomass pulse response method was used to find optimal operation conditions showing no cell/adsorbent interactions. A good correlation was found between the finite bath test and the pulse experiment for a variety of suspensions (intact yeast cells, E. coli homogenate and hybridoma cells) and adsorbents (Streamline Q XL, DEAE and SP), which allows to predict cell/adsorbent interactions in expanded beds just from finite bath adsorption tests. Under the optimised operating conditions obtained using the prior methods, the stability of the expanded bed was investigated during fluidisation in biomass containing feedstock (up to 15% yeast on wet weight basis) employing residence time distribution analysis and evaluation by an advanced model. Based on these studies threshold values were defined for the individual experiments, which have to be achieved in order to obtain an efficient EBA process. Breakthrough experiments were conducted to characterise the efficiency of BSA adsorption from S. cerevisiae suspensions in EBA mode under varying operating conditions. This allowed to correlate the stability of the expanded bed with its sorption efficiency and therefore could be used to verify the threshold values defined. The approach presented in this work provides a fast and simple way to minimise cell/adsorbent interactions and to define a window of operation for protein purification using EBA. PMID- 11787801 TI - Direct process integration of cell disruption and fluidised bed adsorption in the recovery of labile microbial enzymes. AB - The practical feasibility and generic applicability of the direct integration of cell disruption by bead milling with the capture of intracellular products by fluidised bed adsorption has been demonstrated. Pilot-scale purification of the enzyme L-asparaginase from unclarified Erwinia chrysanthemi disruptates exploiting this novel approach yielded an interim product which rivalled or bettered that produced by the current commercial process employing discrete operations of alkaline lysis, centrifugal clarification and batch adsorption. In addition to improved yield and quality of product, the process time during primary stages of purification was greatly diminished. Two cation exchange adsorbents, CM HyperD LS (Biosepra/Life Technologies) and SP UpFront (custom made SP form of a prototype stainless steel/agarose matrix, UpFront Chromatography) were physically and biochemically evaluated for such direct product sequestration. Differences in performance with regard to product capacity and adsorption/desorption kinetics were demonstrated and are discussed with respect to the design of adsorbents for specific applications. In any purification of L asparaginase (pI = 8.6), product-debris interactions commonly diminish the recovery of available product. It was demonstrated herein, that immediate disruptate exposure to a fluidised bed adsorbent promoted concomitant reduction of product in the liquid phase, which clearly counter-acted the product-debris interactions to the benefit of product yield. PMID- 11787802 TI - Direct product sequestration of a recombinant cutinase from batch fermentations of Saccharomyces cerevisiae. AB - The recovery of cutinase of Fusarium solani pisi produced by the yeast Saccharomyces cerevisiae was studied in a fluidised bed adsorption system directly integrated with a productive fermenter (so-called direct product sequestration; DPS). The relative efficiency of this system was compared with the one of a conventional purification process by discrete sequences of fermentation, broth clarification, ultrafiltration and fixed bed anion exchange chromatography. By direct product sequestration of the extracellular heterologous cutinase it was possible, through only one unit operation: (i) to perform broth clarification, (ii) to obtain a high cutinase concentration factor, and (iii) to recover cutinase with a specific activity that equalled that obtained with the conventional purification process. It was also possible (iv) to substantially reduce the total process time, (v) to improve the overall yield, and (vi) to increase cutinase productivity. Furthermore, the procedure outlined is suitable for large scale bioprocess exploitation. PMID- 11787803 TI - High gradient magnetic separation versus expanded bed adsorption: a first principle comparison. AB - A robust new adsorptive separation technique specifically designed for direct product capture from crude bioprocess feedstreams is introduced and compared with the current bench mark technique, expanded bed adsorption. The method employs product adsorption onto sub-micron sized non-porous superparamagnetic supports followed by rapid separation of the 'loaded' adsorbents from the feedstock using high gradient magnetic separation technology. For the recovery of Savinase from a cell-free Bacillus clausii fermentation liquor using bacitracin-linked adsorbents, the integrated magnetic separation system exhibited substantially enhanced productivity over expanded bed adsorption when operated at processing velocities greater than 48 m h(-1). Use of the bacitracin-linked magnetic supports for a single cycle of batch adsorption and subsequent capture by high gradient magnetic separation at a processing rate of 12 m h(-1) resulted in a 2.2 fold higher productivity relative to expanded bed adsorption, while an increase in adsorbent collection rate to 72 m h(-1) raised the productivity to 10.7 times that of expanded bed adsorption. When the number of batch adsorption cycles was then increased to three, significant drops in both magnetic adsorbent consumption (3.6 fold) and filter volume required (1.3 fold) could be achieved at the expense of a reduction in productivity from 10.7 to 4.4 times that of expanded bed adsorption. PMID- 11787804 TI - Cell death in the heart. AB - The role of apoptosis in cardiac disease remains controversial. Much of the apoptosis detected, by chemical or molecular means, reflects inflammatory reaction and responding blood cells rather than myocytes, though their apoptosis in situ may exacerbate a bad situation, and their direct action against myocytes has not been excluded definitely. Myocyte apoptosis may reflect end-stage cardiac failure rather than causing it. If this is the case, then preventing apoptosis so that the cells can undergo necrosis does not accomplish much. Apoptosis is a consistent and important finding in many forms of cardiovascular disease. As determined by ultra-structure, apoptosis is common in cardiomyocytes, fibroblasts, vascular endothelial cells, and smooth muscle cells in cardiovascular disease of many origins. (62) Even though smooth muscle cells in atheromatous plaques appear to be necrotic,l it is likely that this is an evolved situation of apoptotic cells that were not removed. Given the prevalence of apoptotic processes in diseased heart and the very limited capacity of this organ to repair itself, (56) it is appropriate and justified to continue to explore the significance of apoptosis in cardiac disease and, above all, to explore the use of antiapoptotic agents in acute situations. Researchers must pay explicit attention to how they document cell death and in what tissues or cells it occurs. Otherwise, clinicians risk being deluded by preservation of morphology in nonfunctional cells and by confusion of what happened and where death occurred in the sequence of causality. Cell death in the heart is a matter of substantial theoretical and practical concern. A major problem in analyzing it is that, although apoptosis may be demonstrated easily in myocytes, particularly embryonic myocytes, under conditions of culture, interpretation is much more complex in an intact organ. The first issue is one of timing. In situations of severe, acute loss of cells, such as in an infarct, apoptotic cells may not be cleared rapidly and may progress to a more oncotic or necrotic morphology. Second, in situations of inflammation, biochemical or molecular techniques may confound apoptosis of inflammatory cells with apoptosis of myocytes. Third, priorities in the sequence of apoptosis differ between large, generally nonmitotic cells with massive cytoplasm (as differentiated myocytes) and small mitotic cells in culture, which usually are studied. The appearance and many markers of physiological cell death may differ from the most widely recognized forms of apoptosis, including late collapse of the nucleus and primacy of lysosomal or other proteases as opposed to caspases. Investigators should always strive to establish multiple criteria for apoptosis, with good documentation of timing and cell type. When these factors are taken into consideration, it seems that aggressive action against apoptosis may be of value in acute situations, such as infarct, in which buying short increments of time may reduce damage. In more chronic situations, much of the apoptosis detected derives from invading lymphocytes, mast cells, or other cells relating to inflammation. The apoptosis of these cells may exacerbate an already difficult situation, and intervention may prove of value. Otherwise, apoptosis of myocytes is more typically an end-stage situation, and it is more fruitful to alleviate the problem before this stage is reached. PMID- 11787805 TI - Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes. AB - Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure. PMID- 11787806 TI - Apoptosis in atherosclerosis. Does it contribute to plaque instability? AB - Several reports have demonstrated apoptosis in the advanced human atheroma. Most clinical events however, are precipitated by plaque rupture, to a lesser extent erosion, and the development of occlusive thrombi. Whether the extent of apoptosis can influence lesion stability is not precisely known, however, there is emerging data supporting this role. Obvious difficulties arise when studying apoptosis in atherosclerotic plaques because of the complex nature of the disease and lack of an experimental model of plaque instability. This article applies a systematic approach to discuss the issue of apoptosis in context of early disease to complex symptomatic lesions that may become fatal. PMID- 11787807 TI - Apoptosis and caspases. AB - The expedition into the apoptosis signaling pathway, although it has just begun, has resulted in the discovery of a significant number of remarkable signaling molecules at all levels of this novel pathway After the pinnacle of this frenetic cloning effort has been reached, however, it is important to put this pathway and its constituents into a biological and pathophysiological context. It has become clear that cell death does not automatically mean activation of caspases. The recent discovery of a function of effector caspases of the apoptosis pathway outside of apoptosis is currently revolutionizing our view of these seemingly unrelated and rather counteracting processes, cell death and cell proliferation. It appears that caspases play a much more fundamental role in cells than originally expected. PMID- 11787808 TI - Apoptosis in cardiac transplant rejection. AB - Apoptosis occurs in human cardiac allograft rejection and may occur with all degrees of rejection and even in its absence. The prevalence and severity of apoptosis is determined predominantly by the intensity of macrophage infiltration and may be mediated by NO-related mechanisms. Apoptosis of interstitial, endothelial, and inflammatory cells is also present in heart allografts and may influence the degree and extent of vascular injury contributing to allograft rejection. Ongoing apoptosis of inflammatory cells suggests an immunoregulatory role. Studies of the involvement of NO in myocyte damage and Fas-FasL interactions in peripheral tolerance have raised the exciting possibility that these pathways can be exploited in a beneficial way. Further understanding of the role of apoptosis and the cellular and biochemical mechanisms that are involved in cardiac myocyte death and in inflammatory, endothelial, and interstitial cell death may provide insights into therapeutic modalities to suppress allograft rejection and vasculopathy. PMID- 11787809 TI - Apoptosis in the genesis of cardiac rhythm disorders. AB - Programmed cell death has provided a potential pathogenetic mechanism that could play a role in several diseases of the cardiac conduction system and the myocardium that are clinically expressed as disorders of the cardiac rhythm (Fig. 4). Most of these studies have been descriptive. The exact nature of the triggers for apoptotic cell death is not well understood and is a subject of current investigation. Alterations in the architecture of the myocardium play an important role in the pathogenesis of ventricular arrhythmias that are responsible for a large proportion of sudden cardiac deaths. Although apoptosis is essential for normal development, excessive apoptosis resulting from pathological triggers may result in destruction of tissues and in the development of heart disease in which a fatal arrhythmic event may be a final common pathway. At present, the triggers for programmed cell death in disorders of the cardiac rhythm are not understood completely. Because diverse conditions trigger apoptosis, treatment strategies may have to be directed toward attenuating such triggers and, in some instances, toward modifying the process itself. If future therapies that can favorably modulate the apoptotic process in conditions such as dilated cardiomyopathy and postmyocardial infarction are developed, they will have the potential to prevent the pathologic alteration of myocardial architecture that is conducive to arrhythmogenesis. PMID- 11787810 TI - Noninvasive strategies to image cardiovascular apoptosis. AB - Apoptosis consists of a complex set of biochemical events initiated by an array of different stimuli and enzymatic pathways. There is a set of common morphologic and biochemical features of apoptosis that could be exploited as hot or cold targets to image cardiovascular apoptosis. First, the authors review the potential array of targets that can be used to identify apoptosis. Then, the authors examine the history and current status of radiolabeled annexin V, the agent currently used to image apoptosis. PMID- 11787811 TI - Gene therapy and pharmaceutical modulation of apoptosis. AB - Apoptosis is detectable in cardiovascular disease in various forms. Although the methods to detect apoptosis need improvement, and its magnitude is not known clearly, there is sufficient evidence to postulate that it might be important in progression of disease. Clinicians now have some specific compounds that can be used to modulate apoptosis. The preliminary data suggest that we can modulate apoptosis in animal models and that this is associated with obvious benefits in terms of tissue salvage and possibly improved function. There are no human data as yet. Many questions must be addresses before undertaking human studies. Despite these shortcomings, there is a tremendous potential for apoptotic modulation in preventing or ameliorating cardiovascular disease in the near future. PMID- 11787812 TI - Death receptors and apoptosis. Deadly signaling and evasive tactics. AB - The availability of large amounts of sequence data has made it possible to identify death receptors by homology. Because the genome has not been analyzed completely, a few additional members of this family probably will be identified in the next few years. Rapid progress also has been made recently on the signaling mechanisms used by the death receptors. Considerable conservation of the intracellular signaling mechanisms is seen between different receptors suggesting that it is unlikely that new elements will be added to the molecular framework of death receptor signaling. The analysis of signaling mechanisms has exposed the complexity and multiplicity of cellular responses on death receptor activation. It is not surprising, therefore, that understanding the biological function the death receptors lags behind their characterization at the molecular level. In particular, the role of death receptors in many disease states, such as myocardial disease, remains to be elucidated. (38) This complexity in death receptor function has constrained their potential for pharmacological manipulation. In most cases it is not sufficient to simply activate a specific death receptor. Manipulation of only one of the multiple responses induced by the receptor is desirable. Currently, no solutions to this challenge have been applied. The exception to this conundrum may be TRAIL. Injection of recombinant TRAIL has few side effects in animal studies and combination therapies that use TRAIL as a radiation sensitizer show early promise. PMID- 11787813 TI - Involvement of mitochondria in apoptosis. AB - Like in many other cell types, apoptosis can be induced by different stress in cells isolated from the cardiovascular system. The mitochondrial apoptotic pathway can be activated by serum deprivation, (9, 66) staurosporine treatment, (110) and oxidative stress. (14) The cytokine pathway is activated by TNF or Fas. (43, 52, 107) Immunohistochemical analysis of endomyocardial biopsies from patients with congestive heart failure, acute myocardial infarction, ischemic cardiomyopathies, and myocarditis, have led to the identification of apoptotic cardiomyocytes. (15 41, 74) Therefore, the pre-existing death program evidenced in isolated cardiomyocytes also may be activated in cardiomyopathies. Apoptosis also has been detected in vascular diseases, such as atherosclerosis, hypertension, and restenosis.49 It is likely that mitochondria, through permeabilization of their outer membrane, play a major role in many apoptotic responses leading to cardiomyocyte apoptosis. Elucidation of the mechanism whereby mitochondrial cell-death effectors are released in the cytosol should open the opportunity of developing compounds able to regulate the progression of apoptosis. The development of drugs acting on the mitochondrion may allow the prevention or the limitation of the seriousness of many cardiovascular diseases in which apoptosis has been detected. PMID- 11787814 TI - Antiapoptotic proteins. The bcl-2 and inhibitor of apoptosis protein families. AB - The balance between pro- and antiapoptotic proteins can determine cellular fate. In this regard, the Bcl-2 and IAP protein families have evolved as highly conserved regulators of cell death. A further testament to their critical roles in maintaining balance between cell life and death may be the increasing implication of Bcl-2 and TAP proteins in the pathologies of human diseases. Although much has been learned about these families of proteins, future studies of the Bcl-2 and IAP families are sure to hold more exciting discoveries and will continue to reveal new strategies for combating human diseases. PMID- 11787815 TI - Apoptotic proteins. p53 and c-myc related pathways. AB - c-Myc and p53 are two proteins that have critical roles in the regulation of apoptosis and the cell cycle. The authors review how these two proteins are thought to control the opposing events of proliferation and apoptosis and examine whether their well-documented biological roles in tumorigenesis can be applied to the vascular system. PMID- 11787816 TI - Apoptosis in myocardial ischemia, infarction, and altered myocardial states. AB - The work ahead necessary to develop and refine clinically useful antiapoptotic therapy in ischemic-reperfusion injury is daunting. There are many unanswered questions. What is the best method of detecting apoptosis in the cardiac myocytes? What will be the most practical method to deliver this therapy to the cardiac myocyte? Will antiapoptotic agents act selectively on affected myocytes to provide clinical efficacy? Will antiapoptotic agents be effective, or will they be limited by dose heterogeneity? If antiapoptotic is proven to have long lasting efficacy, should it be used for all patients with myocardial infarction or confined only to patients with left ventricular dysfunction. Will antiapoptotic therapy be so effective that it replaces ACE inhibitors and betablockers, or will it always be used as an adjunct to an ACE inhibitor or a betablocker? These questions lay the foundation for investigation for the next decade. PMID- 11787817 TI - Fibre type regionalisation in lower hindlimb muscles of rabbit, rat and mouse: a comparative study. AB - The topographical distribution of different fibre types in muscles of the lower hindlimb in rabbits and mice was quantitatively determined. The results were compared to those previously obtained, using the same new quantification methods, in homologous muscles of the rat. Type I fibres ('slow') were identified using myofibrillar ATPase histochemistry and mapped out at the mid proximo-distal level for 11 'fast' muscles in the rabbit and 7 'fast' muscles in the mouse. For the slow soleus muscle the procedure was undertaken for the type II fibres. Furthermore, for 5 of the 'fast' muscles from each animal species (extensor digitorum longus; flexor digitorum and hallucis longus; gastrocnemius medialis; peroneus longus; tibialis anterior), several more proximal and distal cross sectional levels were also analysed. All the investigated 'fast' muscles showed a significant degree of topographical eccentricity in the midlevel distribution of type I fibres. For most muscles, the direction of this 'vector regionalisation' of type I fibres was similar between the three animal species. For homologous muscles, the degree of vector regionalisation was significantly different: mouse > rat > rabbit. The relative area of the region containing the type I fibres, inversely related to the degree of 'area regionalisation', was also significantly different: mouse < rat < rabbit. Also within each animal species, muscles with a marked degree of vector regionalisation tended to show a marked area regionalisation. Proximo-distal differences in type I fibre density were observed in all the three species of animals; also these patterns showed marked inter species differences. The findings demonstrate the general occurrence of, and systematic relationships between, different aspects of type I fibre regionalisation. The observed interspecies differences suggest that the expression of this phenomenon is adapted to differing functional needs. PMID- 11787818 TI - Effects of the curly tail genotype on neuroepithelial integrity and cell proliferation during late stages of primary neurulation. AB - The curly tail (ct/ct) mouse mutant shows a high frequency of delay or failure of neural tube closure, and is a good model for human neural tube defects, particularly spina bifida. In a previous study we defined distinct domains of gene expression in the caudal region of non-mutant embryos during posterior (caudal) neuropore closure (Gofflot et al. Developmental Dynamics 210, 431-445, 1997). Here we use BrdU incorporation into S-phase nuclei to investigate the relationship between cell proliferation and the previously described gene expression domains in ct/ct mutant embryos. The BrdU-immunostained sections were also examined for abnormalities of tissue structure; immunohistochemical detection of perlecan (an extracellular heparan sulphate proteoglycan) was used as an indicator of neuroepithelial basement membrane structure and function. Quantitation of BrdU uptake revealed that at early stages of neurulation, cell proliferation was specifically reduced in the paraxial mesoderm of all ct/ct embryos compared with wild type controls, but at later stages (more cranial levels) it was increased. Those ct/ct embryos with enlarged posterior neuropore (indicating delay of closure) additionally showed an increased BrdU labelling index within the open neuroepithelium at all axial levels; however, this tissue was highly abnormal with respect to cell and nuclear morphology. It showed cell death and loss of cells from the apical surface, basement membrane defects including increased perlecan immunoreactivity, and increased separation from the underlying mesenchyme and notochord. These observations suggest that the mechanism of delay or failure of neuroepithelial curvature that leads to neural tube defects in curly tail embryos involves abnormalities of neuroepithelial mesenchymal interactions that may be initiated by abnormal cellular function within the neuroepithelium. Minor histological and proliferation abnormalities are present in all ct/ct embryos, regardless of phenotype. PMID- 11787819 TI - Histology and immunohistochemistry of the gut-associated lymphoid tissue of the eastern grey kangaroo, Macropus giganteus. AB - Mesenteric lymph nodes and gut-associated lymphoid tissue (GALT) from juvenile eastern grey kangaroos were investigated. The mesenteric nodes had a similar structure to that described for eutherian mammals. They contained distinct regions of medulla and cortex, with prominent follicles and germinal centres. Gut associated lymphoid tissue consisted of areas of submucosal follicles. These varied from areas of densely packed lymphocytes with darkly staining, prominent coronas to areas with no defined follicles. The distribution of T cells in these tissues was documented by use of species-crossreactive antibodies to the surface markers CD3 and CD5; B cells were identified by antibodies to CD79b. Within the lymph nodes T cells were located mainly in the paracortex and cortex, with limited numbers observed in the follicles; B cells were located on the marginal zone of the follicles. In GALT, T cells were located in the peripheral regions of the germinal centres of secondary follicles, while B cells were abundant in primary follicles. These observations are consistent with those made in a range of other marsupials (metatherian) and eutherian mammals and are indicative of the capacity to respond to antigens entering via the mouth. PMID- 11787820 TI - Vimentin, cytokeratin 8 and cytokeratin 18 are not specific markers for M-cells in human palatine tonsils. AB - Standard immunohistochemical methods were used to detect the presence of vimentin, cytokeratin 8, cytokeratin 18, macrophages and Langerhans cells in the human tonsillar epithelium in formalin-fixed and frozen tissue specimens. Vimentin detection was restricted to infiltrating cells of the lymphoid series, dendritic and vascular endothelial cells. All epithelial cells were negative. Cytokeratin 8 and 18 were readily detected in a large proportion of epithelial cells lining the crypt, but these cells bore no resemblance to the intestinal M cells. Langerhans cells and macrophages were seen in both the oropharyngeal and crypt epithelium and were more common in the latter. This study confirms the presence of antigen-presenting cells, macrophages and Langerhans cells in the tonsillar epithelium and shows that intermediate filament proteins, vimentin, cytokeratin 8 and 18 are unreliable markers for human tonsillar M-cells, if indeed such cells exist in human tonsils. PMID- 11787821 TI - Thoracic origin of a sympathetic supply to the upper limb: the 'nerve of Kuntz' revisited. AB - An understanding of the origin of the sympathetic innervation of the upper limb is important in surgical sympathectomy procedures. An inconstant intrathoracic ramus which joined the 2nd intercostal nerve to the ventral ramus of the 1st thoracic nerve, proximal to the point where the latter gave a large branch to the brachial plexus, has become known as the 'nerve of Kuntz' (Kuntz, 1927). Subsequently a variety of sympathetic interneuronal connections down to the 5th intercostal space were reported and also described as the nerve of Kuntz. The aim of this study was to determine: (1) the incidence, location and course of the nerve of Kuntz; (2) the relationship of the nerve of Kuntz to the 2nd thoracic ganglion; (3) the variations of the nerve of Kuntz in the absence of a stellate ganglion; (4) to compare the original intrathoracic ramus with sympathetic variations at other intercostal levels; and (5) to devise an appropriate anatomical classification of the nerves of Kuntz. Bilateral microdissection of the sympathetic chain and somatic nerves of the upper 5 intercostal spaces was undertaken in 32 fetuses (gestational age, 18 wk to full term) and 18 adult cadavers. The total sample size comprised 99 sides. Sympathetic contributions to the first thoracic nerve were found in 60 of 99 sides (left 32, right 28). Of these, 46 were confined to the 1st intercostal space only. The nerve of Kuntz (the original intrathoracic ramus) of the 1st intercostal space had a demonstrable sympathetic connection in 34 cases, and an absence of macroscopic sympathetic connections in 12. In the remaining intercostal spaces, intrathoracic rami uniting intercostal nerves were not observed. Additional sympathetic contributions (exclusive of rami communicantes) were noted between ganglia, interganglionic segments and intercostal nerves as additional rami communicantes. The eponym nerve of Kuntz should be restricted to descriptions of the intrathoracic ramus of the 1st intercostal space. Any of these variant sympathetic pathways may be responsible for the recurrence of symptoms after sympathectomy surgery. PMID- 11787822 TI - A degeneration-based hypothesis for interpreting fibrillar changes in the osteoarthritic cartilage matrix. AB - The collagen fibrillar architectures in the general matrix of cartilage slices removed from both normal and osteoarthritic femoral heads were examined by both differential interference light microscopy and scanning electron microscopy. Whereas the normal general matrix contained a finely differentiated pseudo-random weave of fibrils developed from an interconnected array of radial elements, the osteoarthritic general matrix was characterised by the presence of structurally distinct regions consisting of strongly aligned radial bundles of fibrils and associated intense tangles or 'knotted' features. Simple structural models were developed to explore possible transformation structures based on two different types of interconnectivity in the three-dimensional fibrillar network. These models support the hypothesis that the distinctive ultrastructural features of the osteoarthritic general matrix can develop as a consequence of largely passive degradative changes occurring in the fibrillar weave originally present in the normal matrix. This could, in principle, occur independently of any new structure that might develop as a consequence of any upregulation of collagen associated with the osteoarthritic process. PMID- 11787823 TI - Ultrastructural study of Betz cells in the primary motor cortex of the human brain. AB - The ultrastructure of Betz cells in the 5th layer of the primary motor cortex of 17 neurologically and psychiatrically normal control individuals was studied. Normal-appearing Betz cells showed a wide range of features including novel electron-dense inclusion bodies (Bunina-like bodies) resembling Bunina bodies characteristic of amyotrophic lateral sclerosis (ALS), accumulations of neurofilaments (10 nm in diameter), bundles of filaments (20-25 nm in diameter) thicker than neurofilaments, lamellar structures, lamellar bodies and structures similar to Hirano bodies. Among these 'abnormal' features, the presence of Bunina like bodies may be an age-related nonspecific degenerative change, since they appeared more frequently in elderly individuals. The presence of these abnormal features--particularly the Bunina-like bodies--in the Betz cells of normal human brains must be considered in the assessment of the pathognomonic significance of such structures in ALS and other neurological diseases that affect the motor cortex. PMID- 11787824 TI - Comparative histochemical composition of muscle fibres in a pre- and a postvertebral muscle of the cervical spine. AB - References to histochemistry are extensive for human limb muscles but occur less frequently in relation to vertebral muscle. Most vertebral muscle literature has been concerned with muscle fibre characteristics in the lumbar and thoracic spine, due in large part to the incidence of low back pain and idiopathic scoliosis. However few studies have investigated the histochemical composition of neck muscles in humans: and, to our knowledge, no previous study has examined the antagonistic longus colli and multifidus muscle pair. In addition, while age related segmental degeneration is most prominent between C5 and C7, it is not known whether these osteoligamentous changes are paralleled by changes in muscle fibre ratio. Tissue blocks comprising muscle and bone from C5-C7 segments were harvested at autopsy from 16 subjects with ages ranging from 4 to 77 years. The prevertebral longus colli and postvertebral multifidus muscle pairs were randomly selected from one or other side in each subject. The tissue was frozen, sectioned and histochemically stained for myofibrillar adenosine triphosphatase. Analysis of muscle fibre types was performed by light microscopy. Wilcoxon paired t-tests were used to ascertain whether intramuscular and intermuscular differences in fibre composition were significant. In addition, correlation and regression analyses were used to determine whether fibre type proportions changed in either muscle with increasing age. The present study has revealed histochemical differences between longus colli and multifidus at the level of the C5-C7 vertebral segments. Multifidus comprises a significantly greater proportion of type I than type II fibres. Longus colli comprises a significantly greater proportion of type II fibres than multifidus. Further there were no changes in fibre type proportion in either muscle with increasing age. These observations suggest that longus colli responds equally to postural and phasic demands, whereas multifidus is predominantly postural. Also it would appear that age related structural alterations in lower cervical segments are not paralleled by changes in muscle fibre ratio. PMID- 11787825 TI - Surgical anatomy of the sural and superficial fibular nerves with an emphasis on the approach to the lateral malleolus. AB - The aim of this study was to investigate the risk and to analyse the significance of laceration of the sural and superficial fibular nerves during the surgical approach to the lateral malleolus. The sural and the superficial fibular nerves, and their branches were dissected under x 3 magnifying lenses in 68 embalmed leg ankle-foot specimens. The specimens were measured, drawn and photographed. In 35% of specimens the superficial fibular nerve branched before piercing the crural fascia, and in all these specimens the medial dorsal cutaneous nerve of the foot was located in the anterior compartment while the intermediate dorsal cutaneous nerve of the foot was located in the lateral compartment. In 35% of specimens the intermediate dorsal cutaneous nerve of the foot was absent or did not innervate any toe. The deep part of the superficial fibular nerve was in contact with the intermuscular septum. Its superficial part was parallel with the lateral malleolus when the nerve pierced the fascia more proximally and oblique to the lateral malleolus when the nerve pierced the fascia distally. In one case the intermediate dorsal cutaneous nerve of the foot was in danger of laceration during a subcutaneous incision to the lateral malleolus. In 7 cases (10%) the sural nerve overlapped or was tangent to the tip of the malleolus. Malleolar nerve branches were identified in 76% of the cases (in 28% from both sources). The sural nerve supplies the lateral 5 dorsal digital nerves in 40% of cases. Our study indicates that during the approach to the lateral malleolus there is a high risk of laceration of malleolar branches from both the sural and the superficial fibular nerves. There is less risk of damage to the main trunk of these nerves, but the 10% chance of laceration of sural nerve at the tip of the malleolus is significant. As the sural nerve supplies the superficial innervation to the lateral half of the foot and toes in 40% of cases, the risk of its laceration is even more important than indicated by the common anatomical teaching. PMID- 11787826 TI - Hypertrophy of mucosa and serosa in the obstructed intestine of rats. AB - After a surgically induced partial obstruction of the small intestine (ileum) in adult rats there is an accumulation of ingesta and a progressive enlargement of the lumen accompanied by wall thickening: over a period of 2-3 wk the circumference of the hypertrophic intestine increases by a factor of 2.7 and the thickness of the musculature increases more than threefold, while the length of the ileum (measured at the mesenteric attachment) remains unchanged. The villi become markedly larger and more elongated in the circumferential direction, and have a greater separation between one another. The number of villi per unit surface is markedly reduced but the number of villi per unit length of ileum, whilst appearing to show a small increase, was not significantly altered. The component epithelial cells (absorptive cells) appear unchanged in morphology and size (height). The microvilli of the epithelial cells have the same appearance, size (height) and packing density in the control and the hypertrophic ileum. Glands of Lieberkuhn, Peyer's patches and single lymphatic follicles constituting the Peyer's patches are significantly increased in size in the hypertrophic intestine. The serosal surface of the hypertrophic ileum, in spite of the great expansion, remains regularly covered by mesothelial cells; these are much larger than in the controls and have an altered distribution of their microvilli. PMID- 11787827 TI - Regional differences in innervation of lymph nodes in the Wistar rat. AB - Previous light microscopic investigations have indicated that, in the rat, the innervation of mesenteric lymph nodes may be less dense than that of axillary nodes. However, nerves of the enteric system are difficult to visualise by light microscopy. Therefore we quantified the density of innervation of axillary and mesenteric lymph nodes at the ultrastructural level. The results show a highly significant difference in the density of innervation between these 2 groups of lymph nodes, but morphologically the type of the innervation does not seem to differ. In previous studies, nerves were found predominantly in regions characterised by aggregations of plasma cells. In view of this association, we suggest that the difference in innervation may reflect the migration of plasma cells out of mesenteric nodes and into the mucosa of the gut wall. By contrast, in peripherally located nodes, plasma cells tend to remain within the lymph nodes, and hence the density of innervation of these nodes is greater. PMID- 11787828 TI - The prognostic factors of adult tuberculous meningitis. AB - BACKGROUND: Our aim was to analyze the prognostic factors and therapeutic outcomes of adult tuberculous meningitis (TBM). PATIENTS AND METHODS: Clinical data of 36 patients with adult TBM were retrospectively identified at our institution over a period of 5 years. RESULTS: 36 adult TBM patients, 23 males and 13 females, aged 16-83 years, were included in this study. The 36 patients were also divided into three groups (stages I, II and III) according to the severity of TBM on admission. Therapeutic outcomes at 3 months were determined using a modified Barthel Index (BI). For the purpose of statistical analysis, the patients were divided into two groups: good outcome (BI > or = 12) and poor outcome (BI < 12). Positive cerebrospinal fluid (CSF) culture was found in 47% (17/36) of patients and isoniazid-resistant strains were found in 18% (3/17) of culture-proven TBM. We statistically compared clinical manifestations, CSF features and therapeutic results of the two patient groups. Significant prognostic factors included severity of TBM at the time of admission, the presence of headache, fever, hydrocephalus, high CSF protein concentration and high CSF lactate concentration. In stepwise logistic regression analysis, only the presence of hydrocephalus and severity of TBM on admission were strongly associated with therapeutic failure even after adjusting for other potentially confounding factors. CONCLUSION: In Taiwan, TBM is an important public health issue and the emergence of resistant strains of this disease in recent years presents a therapeutic challenge. Because delay in diagnosis is directly related to poor outcome, early diagnosis and early treatment are essential for survival. PMID- 11787829 TI - Adults with meningitis caused by viridans streptococci. AB - BACKGROUND: We analyzed the clinical features and therapeutic outcomes of adults with meningitis caused by viridans streptococci. PATIENTS AND METHODS: 12 adult patients with meningitis caused by viridans streptococci were enrolled in this study. Clinical data were collected over a period of 15 years. RESULTS: Of the 12 patients, 11 patients had community-acquired meningitis, while one had nosocomially acquired meningitis. 11 contracted the spontaneous form and one contracted the postneurosurgical form. All isolates were susceptible to penicillin. The portals of entry of infection were determined in all 12 patients; five patients had otopharyngeal infections with or without their being spread hematogenously. The infections in six patients were spread hematogenously, but one of them was spread hematogenously with endocarditis. One patient became infected after a craniotomy. The patients infected by viridans streptococci had a high incidence of focal suppuration and cerebral vasculitis but no deaths occurred. CONCLUSION: Adult bacterial meningitis caused by viridans streptococci is not uncommon and otopharyngeal infection appears to be an important portal of entry. Clinical manifestations varied according to the different underlying conditions. The results of this study also demonstrate the high incidence of intracranial focal suppuration and cerebral vasculitis concomitant with meningitis. Penicillin remains the treatment of choice for patients with meningitis caused by viridans streptococci. Therapeutic outcome is favorable for patients who receive prompt treatment. PMID- 11787830 TI - Long-term seropositivity against Echinococcus multilocularis in an epidemiological follow-up study in southwestern Germany (Romerstein). AB - BACKGROUND: Out of 2,560 participants in an epidemiological survey of alveolar echinococcosis (AE) performed in 1996 in southwestern Germany, 47 participants had tested seropositive in one of two crude antigen screening ELISAs and were inconspicuous on hepatic ultrasound. PATIENTS AND METHODS: Out of these 47 seroreactors, 36 attended a follow-up examination 30 months after the primary examination, including ultrasound and serology with various Echinococcus multilocularis-specific antigens. RESULTS: No lesion suspicious for AE was detected in any participant. Serology showed only minor changes as compared to the earlier results. CONCLUSION: Persistent seropositivity without detectable hepatic lesions could be interpreted as an early sign of sonographically not yet detectable AE, immunity to E. multilocularis or unspecific serological reactivity. For seropositive and clinically inconspicuous inhabitants of areas endemic for AE follow-up examinations at intervals of 2-3 years seem to be adequate. PMID- 11787831 TI - Association between multiple sclerosis and cystic structures in cerebrospinal fluid. AB - BACKGROUND: The aim of the study was to search for infectious agents in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). PATIENTS AND METHODS: CSF from ten patients with the diagnosis relapsing remitting MS and from five controls without MS were examined by transmission electron microscopy (TEM), dark field microscopy (DF), interference contrast microscopy (ICM) and UV microscopic examination of acridine orange staining (AO). All CSF samples from patients and controls were cultured. RESULTS: Cystic structures were observed in CSF of all ten patients by AO and TEM. DF revealed eight cyst-positive patients out of nine. One of five control persons had such structures in the CSF; this person had suffered from erythema migrans. Spirochete or rod-like structures emerged after culturing two of the MS patient CSF samples and these structures could be propagated. CONCLUSION: A significant association of CSF cysts and MS was identified in this small study among residents in a coastal area of southern Norway. The cysts could be of spirochetal origin. Our study may encourage other researchers to study larger patient groups. PMID- 11787832 TI - Hospitalization decision for ambulatory patients with community-acquired pneumonia: a prospective study with general practitioners in France. AB - BACKGROUND: We designed a prospective study in the Puy-de-Djme region of France to identify factors associated with a hospitalization decision by general practitioners (GPs) for patients with community-acquired pneumonia (CAP). PATIENTS AND METHODS: 95 voluntary GPs were recruited to report over the period (February 1993 to March 1994) patients diagnosed with CAP defined as acute onset of fever associated with focal pulmonary crackles and/or radiological changes consistent with a pulmonary infection in patients over 3 years of age, living in the community. RESULTS: 37 of the 175 CAP patients (21.4%) were hospitalized. Univariate analysis showed that the hospitalization decision was related to age > 65 years, retirement, history of cardiovascular disease, other extrapulmonary chronic disease, chest auscultation findings, tachypnea at rest and altered mental status. Multivariate analysis identified four variables associated with hospitalization: living alone at home (OR = 3.75), history of cardiovascular disease (OR = 2.54), other chronic medical conditions excluding pulmonary diseases (OR = 4.28) and tachypnea at rest (OR = 3.33). The hospitalization decision by GPs for patients with CAP takes into account social conditions, co morbid conditions of the patients and the seventy of CAP. PMID- 11787833 TI - The penetration of ciprofloxacin into human pancreatic and peripancreatic necroses in acute necrotizing pancreatitis. AB - BACKGROUND: Antibiotic prophylaxis in necrotizing pancreatitis has recently gained acceptance. Published studies, however, used different antibiotic regimes and some antibiotics penetrated pancreatic tissue or pancreatic necroses only poorly. The aim of this study was to assess the penetration of ciprofloxacin (CIP) into necrotic pancreatic and peripancreatic tissue. PATIENTS AND METHODS: Serum, pancreatic necroses, peripancreatic fat tissue necroses and infected omental fluid levels of CIP were measured after 51 operations in 14 patients. RESULTS: The median penetration ratio of CIP was 137.5% (range 11-196%) in infected omental bursa fluid, 59.6% (3-214%) in pancreatic necroses and 67.1% (1 250%) in peripancreatic necroses. Chemotherapeutical ratios of CIP as a marker for antimicrobial potency were high against most relevant pathogens in necrotizing pancreatitis. CONCLUSION: Due to its antimicrobial spectrum and the good penetration into the relevant compartments, CIP may be useful in preventing local infection in necrotizing pancreatitis. PMID- 11787834 TI - Clinical quiz. Intrasellar mass lesion--a difficult diagnosis. PMID- 11787835 TI - Osteomyelitis: etiology, diagnosis, treatment and outcome in a public versus a private institution. AB - BACKGROUND: Although bone infections are difficult to diagnose and manage, primary health care providers often give comprehensive care to patients with few referrals. To evaluate how trends in care impact upon management of bone infections, we performed a retrospective review of medical records of 198 osteomyelitis patients. PATIENTS AND METHODS: 130 patients were hospitalized at a private institution and 68 were hospitalized at a public (teaching) institution. Outcomes measured were bone salvage or loss in relation to predisposing co morbidities and infectious disease (ID) physician involvement in the patient care. RESULTS: Co-morbidities predominating at the public and private hospitals, respectively, were presence of metal implants (20% and 37%) and diabetes (32% and 31%). The most common pathogens at the public and private hospitals, respectively, were methicillin-susceptible Staphylococcus aureus (MSSA, 16 and 32%) and methicillin-resistant S. aureus (MRSA, 3% and 31%). ID specialists treated longer with i.v. antibiotics (42 and 43.5 median treatment days) than non ID specialists (14 and 7 median treatment days). When ID specialists were involved in case management, a trend to bone salvage was seen at the public hospital (p < 0.09). CONCLUSION: Osteomyelitis patient outcome varies less by hospital setting than by case management. PMID- 11787836 TI - Nocardial brain abscess: observation of treatment strategies and outcome in Switzerland from 1992 to 1999. AB - BACKGROUND: Brain abscesses caused by Nocardia spp. are rare, but life threatening infections that are notoriously difficult to diagnose and treat and which occur mainly in immunocompromised patients. Standard treatment guidelines are not available. METHODS: A systematic search for nocardial brain abscesses from 1992 to 1999 was conducted in Switzerland for the comparison of clinical presentation, treatment strategies and outcome. RESULTS: Seven cases were found, for which data of six were available. In 4/6 patients antimicrobial therapy led to a decrease in the size of abscesses. Four of six patients died. The cause of death was likely due to underlying co-morbidities, rather than the nocardial infection. CONCLUSION: The finding that treatment was different in each case underscores the lack of therapeutic guidelines. PMID- 11787837 TI - Safety and immunogenicity of a yeast-derived recombinant hepatitis B vaccine in Bulgarian newborns. AB - BACKGROUND: In 1998, Bulgaria adopted a recombinant DNA yeast-derived hepatitis B (HB) vaccine (Euvax B) for universal vaccination of all Bulgarian newborns on a 0 1-6 month schedule, the first dose to be given within 24 h of birth. MATERIALS AND METHODS: We evaluated the safety, immunogenicity and effectiveness of this vaccine in over 40,000 healthy infants from July 1998 to December 1999. Standard safety information was collected for all infants vaccinated, subsets being followed for solicited local and systemic adverse events (n = 200) and antibodies to HB surface antigen (anti-HBsAg) 1-3 months after the third dose (n = 140). RESULTS: No serous adverse events were registered for any vaccinee, solicited local reactions were rare (< 1.5%), mild and transient. The overall geometric mean titer (GMT) was 1,012 mIU/ml (95% CI: 786; 1,302), the seroprotection rate being 98.6%. CONCLUSION: These surveillance data, obtained under the conditions of universal infant immunization show the novel recombinant HB vaccine, Euvax B, is safe and well-tolerated with an immunogenicity similar to other recombinant HB vaccines. PMID- 11787838 TI - Spontaneous gram-negative cellulitis in a liver transplant recipient. AB - A 47-year-old liver transplant recipient developed fever and cellulitis on the 8th post-transplant day. The clinical appearances were of a rapidly advancing cellulitis. The patient had a past history of severe peripheral edema and hypoalbuminemia. Blood cultures and skin biopsy grew Escherichia coli. To our knowledge, this is the first reported case of E. coli cellulitis in a liver transplant recipient. However, cases have previously been described in patients with cirrhosis or idiopathic nephritic syndrome, conditions which share predisposing features of peripheral edema and hypoalbuminemia. Bacteremic gram negative cellulitis should be considered in compromised patients with unusual presentations of cellulitis. PMID- 11787839 TI - Retroperitoneal suppurative lymphadenitis complicating Staphylococcus aureus acute bacterial endocarditis. AB - Acute bacterial endocarditis is commonly caused by Staphylococcus aureus. Acute bacterial endocarditis due to S. aureus is often complicated by metastatic infection to distant organs, i.e. the central nervous system, the heart, lungs, kidneys and joints. However, metastatic lymph node involvement has not been reported. This is a case report of S. aureus acute bacterial endocarditis complicated by metastatic suppurative lymphadenitis of retroperitoneal lymph nodes. We believe this is the first reported case of suppurative lymphadenitis of the mesenteric lymph nodes secondary to S. aureus acute bacterial endocarditis. PMID- 11787840 TI - Reactivation of hepatitis C virus superinfection in a patient seropositive for hepatitis B e antigen. AB - During the course of chronic hepatitis B virus (HBV) infection, a patient seropositive for hepatitis B e antigen experienced four episodes of acute hepatic necroinflammation. Serum HBV-DNA concentration elevated immediately before the first and third exacerbations, whereas serum hepatitis C virus (HCV) RNA was detected during the second and fourth exacerbations. The nucleotide sequences of HCV hypervariable region derived from samples of the two exacerbations were identical. Interestingly, "de novo" seroconversion of anti-HCV antibody (Abbott HCV EIA 3.0) followed by reversion occurred in both the second and fourth exacerbations with low sample/cutoff ratios. Immunoblot analysis using a line immunoassay (Inno-LIA HCV Ab III) revealed a single positive band (C1) developing after the second exacerbation. These data indicate that the second exacerbation in this patient was caused by newly acquired acute HCV superinfection, whereas the fourth exacerbation was likely due to reactivation of the previous HCV infection. Recognition of such a case suggests that the presence of de novo seroconversion of anti-HCV may indicate either reactivation or acute superinfection of HCV in a patient seropositive for hepatitis B e antigen. PMID- 11787841 TI - Localized lymphadenopathy due to leishmanial infection. AB - A 25-year-old female patient presented with an isolated cervical lymph node enlargement several months after having returned from Spain and Latin America. She had no other signs or symptoms of disease. Leishmania infantum/chagasi was identified as the causative agent. With extended travel activities localized lymph node enlargement due to leishmanial infection should be included in the differential diagnosis of lymphadenopathy of unknown origin. PMID- 11787842 TI - Herpes simplex encephalitis--an atypical case. AB - Herpes simplex virus (HSV) is a common cause of viral encephalitis. Herpes simplex encephalitis (HSE) typically presents with acute neurologic changes and the initial cerebrospinal fluid examination is nearly always abnormal. We report a case of a patient with HSE and normal initial CSF analysis. This resulted in delayed diagnosis and therapy with subsequent severe neurolgical sequelae. Herpes simplex infection should be included in the differential diagnosis of encephalopathic patients and a normal CSF examination. PMID- 11787843 TI - A probable case of herpes simplex encephalitis despite negative PCR findings. AB - A 54-year-old woman was admitted to the hospital suffering from fever and personality changes. Laboratory examination of her cerebrospinal fluid (CSF) showed 270 mononuclear cells, 30 polynuclear cells and a clinically low number of erythrocytes/mm3. Empirical clinical findings from this case suggested treatment with acyclovir. Magnetic resonance imaging (MRI) showed bilateral temporal hyperintense signals in T2-weighted images. PCR with specific primer for herpes simplex virus type 1 (HSV-1) and HSV-2 were negative. There was no elevation of oligoclonal antibodies specific to HSV in CSF after 2 weeks. Although we did not prove the presence of the agent microbiologically at the clinical onset of the disease, the MRI and electroencephalogram (EEG) findings, erythrocytes in CSF and the dramatic response to acyclovir therapy are suggestive of a diagnosis of herpes simplex encephalitis (HSE). PMID- 11787844 TI - Evidence of HIV-2 infection in northern Italy. PMID- 11787845 TI - Defective E-cadherin/catenin complexes in human cancer. AB - Cancer is caused by a series of genomic changes leading directly or indirectly to disturbance of growth, differentiation and tissue integrity. Genomic, transcriptional or posttranscriptional alterations of E-cadherin/catenin complexes that are implicated in various steps of cancer development comprise mutational inactivation, transcriptional downregulation of E-cadherin sometimes accompanied by upregulation of N-cadherin, proteolysis of E-cadherin and posttranslational stabilisation of beta-catenin and plakoglobin. The E cadherin/catenin complex serves not only cell-cell adhesion but also transduces signals to the nucleus and to the cytoskeleton, either directly or through its connections with multiple other complexes. We review here the expression of E cadherin/catenin in human cancers, emphasising methods of observation and prognostic interpretation of results. This is illustrated in thyroid lesions from the benign follicular adenoma to the extremely malignant anaplastic carcinoma. The eye is an organ largely neglected by students of cadherins and catenins. The implication of a variety of members of these molecular families in the embryonic development of the eye strongly suggests that disturbances of cadherin/catenin complexes are crucial also in the development of ocular tumours. PMID- 11787846 TI - TT virus-related acute recurrent hepatitis. Histological features of a case and review of the literature. AB - TT virus is a recently discovered virus, of which the pathogenetic potential is still uncertain. The present paper describes the histopathological features of a case of TT virus-related acute recurrent hepatitis. The patient is a 28-year-old woman with no history of drug or alcohol abuse, presenting with repeated episodes of hypertransaminasemia evidenced during the last 4 years. No other markers of viral or autoimmune disease were found. On histological analysis, the liver parenchyma showed a preserved architecture. The histological features were those of a mild acute hepatitis. The clinicopathological findings suggest th PMID- 11787847 TI - A comparative study of E-cadherin and stromelysin-3 expression in de novo and ex adenoma carcinoma of the colorectum. AB - An apparent exception to the colorectal adenoma-carcinoma carcinogenetic pathway is the so-called "de novo" carcinoma which has no evidence of adenoma in its vicinity. Despite the fact that they are often quite small, these lesions appear to be more aggressive (i.e., greater likelihood of lymph-node metastases) than carcinomas that clearly arise from surrounding adenomas exadenoma carcinoma. The purpose of the present comparative immunohistochemical study was to compare rates of cell adhesion molecule (E-cadherin) and protease [stromelysin-3 (ST-3)] expression in groups of de novo (n=64) and ex adenoma (n=42) lesions in order to see whether their more aggressive behavior is associated with decreased cell adhesion and increased protease expression. The rates of extensive ST-3 expression and decreased E-cadherin expression were significantly higher in the de novo group (P=0.014 and 0.005, respectively). Histopathologically, the de novo group also had a significantly higher percentage of cases with an infiltrative invasion pattern. These differences highlight the more aggressive phenotype of the de novo colorectal carcinoma and fit with their greater invasive potential. PMID- 11787848 TI - Spindle cell myoepithelial tumours of the parotid gland with extensive lipomatous metaplasia. A report of four cases with immunohistochemical and ultrastructural findings. AB - We report four cases of parotid gland tumours composed predominantly of spindle shaped myoepithelial cells and mature adipocytes. The central portion of one tumour showed extensive adipose differentiation, whereas in the peripheral parts there were small foci of ductal epithelium arranged in cords and tubules within an abundant myxoid stroma. The other cases were adipose spindle cell myoepitheliomas without an obvious glandular component. Under high-power examination, a transition between modified spindle-shaped myoepithelial cells and adipocytes was observed, and this was confirmed with immunohistochemistry. Ultrastructurally, the modified myoepithelial cells showed intracytoplasmic tonofilaments, bundles of actin microfilaments and lipid droplets. A possible pathogenesis is proposed of true metaplastic transformation of myoepithelial cells to adipocytes. This lesion is important to identify correctly, as inadequate surgery can lead to recurrence. PMID- 11787849 TI - Benign tumors of the breast with multinucleated stromal giant cells. Immunohistochemical analysis of six cases and review of the literature. AB - The authors present six cases of benign tumors of the breast with numerous multinucleated stromal giant cells (MSGC). All six patients were women aged 37-70 years (mean 48 years), presenting clinically with a breast mass 1.0-3.8 cm in size (mean 1.9 cm; median 1.5 cm). By standard H&E examination, all cases showed the presence of numerous MSGC haphazardly dispersed within the tumor stroma. Three cases revealed MSGC merging into the surrounding adipose tissue simulating infiltrative growth. The MSGC appeared to have multiple nuclei (5 to 25) with fine chromatin and sporadic small nucleoli. Their cytoplasm was inconspicuous. The MSGC expressed vimentin only and to lesser extent CD34. These cells were negative for muscle markers, keratins, S-100 protein, vascular markers, CD68 and hormone receptors. Interestingly, the majority of MSGC and mononuclear stromal cells showed reactivity for p53 protein and Ki-67 proliferation antigen. All patients were treated by simple excision and remain free of recurrence (mean 70 months, median 48 months.). The reactivity of p53 in MSGC and mononuclear stromal cells may play a key role in linking these two cell types. Nonetheless, the presence of MSGC does not alter prognosis of otherwise typical benign lesions. PMID- 11787850 TI - Genetic alterations in poorly differentiated endocrine colon carcinomas developing in tubulo-villous adenomas: a report of two cases. AB - The genetic study of two cases of tubulovillous adenoma associated with poorly differentiated endocrine carcinoma (PDEC) is reported. Aim of this work was to assess whether the exocrine and endocrine growths share a common genotype. The analysis entailed the search for allelic loss (LOH) or imbalances of polymorphic microsatellite markers at the corresponding chromosomal loci of the genes MEN-1 (11q13), p53 (17p13). Deleted in Colorectal Carcinoma (DCC) (18q21) and hMSH-2 (BAT26) (2p21-22). Additionally, the exons 5-8 of the p53 gene were sequenced in the two PDECs only. One of the two cases investigated showed LOH for 18q DCC markers in the tubulo-villous adenoma while a point mutation of the p53 gene was observed in the PDEC component. No genetic abnormality was observed in both adenoma and PDEC components of the other case. In the two cases p53 protein accumulation was observed in both PDEC and adenoma cells. These data indicate that only the p53 gene abnormality is shared by both colon cancer and PDEC in the two cases reported. The lack of other common genetic defect may suggest a different histogenesis for the two tumor types. The development of colon PDEC implies the defect of p53 gene. PMID- 11787851 TI - Carcinomas of the anal canal and anal margin differ in their expression of cadherin, cytokeratins and p53. AB - Carcinomas of the anus are subdivided into those of the anal canal and those of the anal margin. It has been postulated that the various types of tumours of the anal canal represent a spectrum of differentiation rather than tumours of a separate origin. We compared the expression of Pan-cadherin, cytokeratins (CKs) 5/6, 7, 13, 18 and 19, p53 and MIB-1 in 17 cases of carcinoma of the anal canal and 5 cases of carcinoma of the anal margin. Expression of Pan-cadherin was decreased in 70% of carcinomas of the anal canal but preserved in all five carcinomas of the anal margin. Most of the carcinomas of the anal canal expressed all of the CKs studied. Carcinomas of the anal margin showed expression of CK 5/6 and CK 13, whereas CK7, CK18 and CK19 were rarely expressed. Loss of expression of CK 18 and 19, but not CK 7, is a marker of dedifferentiation in anal canal carcinoma. Of the carcinomas of the anal canal and anal margin, 46% and 80%, respectively, expressed p53. The immunhistochemical findings support the opinion that the various subtypes of carcinoma of the anal canal represent variants in differentiation of squamous cell carcinomas of the anal canal. They confirm the separate histogenetic origin of tumours from the anal canal and anal margin. PMID- 11787852 TI - Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. AB - The increasingly popular use of somatostatin analogs in clinical practice for both diagnostic and therapeutic purposes prompted extensive investigations on somatostatin receptor (sst) expression in human tumors by autoradiography, nucleic acid analysis and, recently, immunohistochemistry (IHC). The currently employed radiotracer for scintigraphy (Octreoscan) is octreotide, a somatostatin analog having a high affinity for sst types 2, 3, and 5. In this study on 25 patients, we compared sst 2, 3, and 5 expression in surgical and biopsy specimens of lung tumors, as revealed by immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR), with the octreoscan outcome (which was positive in 20/25 cases). By IHC, the tumors mainly expressed sst2 (17/25, 68%) at the cell membrane level, while sst 3 and 5 were detected in a fraction of cases (24% and 20%, respectively). Comparing RT-PCR and IHC data, a correlation was found in 83.3% of cases, while octreoscan findings and sst expression were correlated in 22/25 cases (88%). In addition, cytological and biopsy specimens expressed the same sst type found in the corresponding surgical sample, thus indicating that a cell membrane sst immunoreactivity in a biopsy reliably predicts the tumor-receptor profile before its resection. Finally, sst expression was not restricted to neuroendocrine lung tumors, but was also a feature of some non-neuroendocrine carcinomas, although to a lesser extent. The occasional expression of sst subtypes in intratumoral lymphocytes, endothelia and necrotic areas is an additional feature to be considered in the interpretation of Octreoscan findings, since the in vivo procedure does not allow to define the sst cellular distribution. IHC can therefore be usefully coupled to radionuclear investigations to better characterize the sst cellular location and subtype in lung tumors. PMID- 11787853 TI - Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4. AB - The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. We analyzed 22 cell lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. Alterations in p16INK4a were found in all cases and included nine homozygous deletions, seven mutations and promoter methylation in six cases. Eight cell lines (36%) had an alteration of DPC4, including one mutation and seven homozygous deletions. The most typical mutational profile involved K-ras, p53, and p16INK4a, concurrently aberrated in 20 cases (91%). Eight cell lines had alterations in all four genes. Inactivation of DPC4 was always accompanied by alteration of all of the other three genes. This comprehensive data regarding the cumulative genetic alterations in pancreatic carcinoma cell lines will be of great value for studies involving drug sensitivity or resistance that may be associated with inactivation of a particular gene or molecular pathway. PMID- 11787854 TI - Promoter-specific transcription of the IGF2 gene: a novel rapid, non-radioactive and highly sensitive protocol for mRNA analysis. AB - The human insulin-like growth factor-II (IGF2) is a regulatory peptide which is critical in normal fetal growth. IGF2 gene transcription is controlled by the usage of four promoters P1-P4 of which promoters P2-P4 are genomically imprinted. Disruption of imprinting and the resulting increase of gene dosage have been shown to be implicated in tumor progression in a variety of human tumors. Due to the need for high amounts of tissue material for conventional methods such as Northern blotting or ribonuclease protection assay (RPA), studies on IGF2 expression have most often been limited to the detection of total IGF2 transcript, though different dysregulatory events can be responsible for the abundance of IGF2 mRNA found in many tumors. We established a highly sensitive competitive RT-PCR assay for the four different transcripts of the IGF2 gene with transcript-specific external RNA competitors in which we take advantage of fluorescence-based quantification on a semiautomated sequencer. The amount of total RNA needed is approximately 100 times lower than the amounts required for Northern blotting or RPA, so that even cytological samples can be analyzed. We applied the assay to a series of eleven hepatoblastomas (HB) in which normal adjacent liver tissue could also be analyzed. PMID- 11787855 TI - Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats. AB - Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period. PMID- 11787856 TI - Severe bronchiolitis in acute Mycoplasma pneumoniae infection. AB - We report on a 17-year-old patient with severe bronchiolitis due to Mycoplasma pneumoniae infection. Despite an early 10-day course of clarithromycin, she developed progressive dyspnea, cough, fever, and severe obstructive ventilatory impairment. Sixteen days after onset of the disease a severe hemolytic anemia developed with only cold agglutinins positive at serologic screening. Thoracoscopic lung biopsy revealed diffuse bronchiolitis with suppurative intrabronchiolar inflammation, lymphohistiocytic "cuffing" of the bronchioli, and foam cell aggregates within neighboring alveoli. The infiltrate consisted mainly of CD3+, CD8+ lymphocytes and CD68+ macrophages. The diagnosis of Mycoplasma pneumoniae bronchiolitis was based on repeated complement fixation tests, which turned strongly positive only at day 74 after onset of the disease. Pulmonary function improved slowly under long-term prednisone treatment. PMID- 11787857 TI - Spitzoid malignant melanoma with lymph-node metastasis. Is a copy-number loss on chromosome 6q a marker of malignancy? AB - Distinction of spitzoid malignant melanomas (SMM) from Spitz nevi may be difficult or even impossible on the basis of conventional histology. In this report, a patient suffering from a primary lesion diagnosed as a Spitz nevus and a metastatic malignant melanoma approximately 4 years thereafter is described. A diagnosis of SMM was made subsequently upon review of the primary lesion. In the present analysis, we used comparative genomic hybridization (CGH) to define markers characteristic of SMM. The primary lesion revealed deletions on chromosomes 6q and 9p. In the metastasis, additional deletions on chromosomes 10p and 10q and gains of chromosome 7 were found. To our knowledge, no chromosomal aberration on chromosome 6 was hitherto demonstrated in benign melanocytic nevi. Findings reported in the literature suggest that human melanoma metastasis suppressor gene maps to 6q. In contrast, losses on chromosome 9p seem to be an early event in the development of melanoma. However, they are not only found in melanomas but are occasionally present in Spitz nevi as well as in atypical nevi. The CGH result with deletion of 6q in this difficult to diagnose primary melanocytic lesion strongly supports the diagnosis of malignant melanoma. To demonstrate the reliability of loss on chromosome 6q as a marker of SMM, a larger number of lesions must be investigated. PMID- 11787858 TI - Hematotoxicity and blood glutathione levels after cisplatin treatment of tumor bearing mice. AB - The involvement of glutathione, a major cellular antioxidant, in cisplatin mediated development of various hematological changes in mice bearing ascites Dalton lymphoma tumor was investigated. With tumor growth, glutathione levels decreased in blood but increased in tumor cells. Cisplatin treatment of tumor bearing mice caused a decrease in glutathione levels in blood, ascites supernatant, and tumor cells. Blood hemoglobin, erythrocytes, packed cell volume and leukocytes (eosinophils, basophils, and lymphocytes) were also decreased along with the development of various morphological abnormalities in erythrocytes (microcytes, macrocytes, echinocytes, acanthocytes, etc.) after cisplatin treatment. All these hematotoxic features were noted to be increased more when buthionine sulfoximine (a specific glutathione-depleting agent) was also given prior to cisplatin treatment. However, combination treatment of cysteine (precursor for glutathione synthesis) plus cisplatin resulted in an improvement in the glutathione levels and decrease in hematological toxicities. It is noted that the glutathione levels in blood and abnormalities in erythrocytes and other hematological parameters are inversely related in cisplatin-mediated cancer chemotherapy. It is suggested that blood glutathione may play an important role in the development of cisplatin-mediated hematological toxicity in the host. PMID- 11787859 TI - Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death. AB - Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD. cDNA expression array of PCD in K562 cells failed to reveal the presence of Bax at the gene transcript level, which suggests that this cell death process does not require de novo protein synthesis. Treated JM1 cells, on the other hand, showed an increase in the expression of Bcl-2 protein in both forms of cell death, but failed to show Bax expression. The role of other members of the Bcl-2 family remained negligible. Caspase-3 activation was observed in apoptosis of K562 cells but not in BCD or in sanguinarine-treated JM1 cells. These results suggest that sanguinarine in K562 cells induces apoptosis through increasing Bax and activating caspase-3, whereas sanguinarine-induced BCD involves neither. These results also suggest that in JM1 cells, Bcl-2 may play a role in susceptibility of cells to induction of apoptosis and BCD. PMID- 11787860 TI - The myosin ATPase inhibitor 2,3-butanedione-2-monoxime disorganizes microtubules as well as F-actin in Saccharomyces cerevisiae. AB - Interactions between microtubules and filamentous actin (F-actin) are essential to many cellular processes, but their mechanisms are poorly understood. We investigated possible roles of the myosin family of proteins in the interactions between filamentous actin (F-actin) and microtubules of budding yeast Saccharomyces cerevisiae with the general myosin ATPase inhibitor 2,3-butanedione 2-monoxime (BDM). The growth of S. cerevisiae was completely inhibited by BDM at 20 mmol/L and the effect of BDM on cell growth was reversible. In more than 80% of BDM-treated budding yeast cells, the polarized distribution of F-actin was lost and fewer F-actin dots were observed. When cells were synchronized in G1 with alpha-factor and released in the presence of BDM, cell number did not increase and cells were mainly arrested in G1 DNA content without any bud, suggesting that myosin activity is required for new bud formation and the start of a new cell cycle. More than 10% of the BDM-treated cells also revealed defects in nuclear migration to the bud neck as well as in nuclear shape. Consistent with these defects, the orientation of mitotic spindles was random in the 57% of cells treated with 20 mmol/L BDM and immunostained with anti-tubulin antibody. Furthermore, microtubule structures were completely disorganized in most of the cells incubated in 50 mmol/L BDM, while similar amounts of tubulin proteins were present in both BDM-treated and untreated cells. These results show that the general myosin inhibitor BDM disorganizes microtubule structures as well as F actin, and suggest that BDM-sensitive myosin activities are necessary for the interaction of F-actin and microtubules to coordinate polarized bud growth and the shape and migration of the nucleus in S. cerevisiae. PMID- 11787861 TI - Prevention of organochlorine-induced inhibition of gap junctional communication by chaetoglobosin K in astrocytes. AB - Innumerable toxic substances present in the environment inhibit gap junctions, intercellular membrane channels that play fundamental roles in coordinated function of cells and tissues. Included are persistent organochlorine compounds, which pose health risks to humans and animals owing to their widespread use, bioaccumulation, and ability to inhibit gap junction channel-mediated intercellular communication in liver, lung, skin, heart, and brain cells. In this study, the organochlorine xenobiotics dieldrin and endosulfan, at micromolar concentrations, were found to inhibit gap junction-mediated intercellular communication and induce hypophosphorylation of connexin 43 in cultured rat astrocytes, the predominant cell type in the brain coupled through gap junctions. This inhibition of gap junctional communication was substantially reduced by preincubation with chaetoglobosin K (ChK), a bioactive natural produce previously shown to have ras tumor suppressor activity. Chaetoglobosin K also prevented dieldrin and endosulfan-induced hypophosphorylation of connexin 43 and prevented dieldrin-induced connexin 43 plaque dissolution in both astrocytes and cultured liver epithelial cells. The results suggest that stabilization of the native, phosphorylated form of connexin 43 by ChK may contribute to its ability to prevent organochlorine-induced inhibition of gap junction-mediated communication and dissolution of gap junction plaques within the plasma membrane. PMID- 11787862 TI - Molecular properties and metabolic effect on blood cells produced by a new toxin of Enterobacter cloacae. AB - A new toxin of Enterobacter cloacae able to lyse erythrocytes and leukocytes was found. Purification of the toxin was performed by salt precipitation, gel filtration, ion exchange and HPLC in C8 column. SDS-PAGE electrophoresis showed more than one bank corresponding to the leukotoxin able to form polymers and aggregate like some pore-forming cytotoxins (RTX). In culture supernatant the toxin showed 1 HU/ml (hemolytic unit) and 1.5 LU/ml (leukotoxic unit); after purification it reached 15 HU/ml and 20 LU/ml. The ratio between HU and percentage red cells affected the lytic capacity. E. cloacae toxin stimulated the oxidative metabolism of neutrophils, but over 50 microg toxin/ml the stimulus ceased as it was shown by NBT assay due to cell death. Chemiluminescence evidenced an increase in superoxide anion generation, but an excess of toxin interfered with this stimulus, as was previously observed in HlyA Escherichia coli toxin. Cross-reaction was found by immunoblotting with this HlyA. E. cloacae toxin presented higher amounts of proline, valine, aspartic and glutamic acids than HlyA. E. cloacae toxin was similar to HlyA in the prescence of a glycine rich DNA sequence and in the observed effect of calcium on toxin activity. E. cloacae toxin did not cross-react by immunoblotting with hemolysin HmpA of Proteus. PMID- 11787863 TI - Serum carnitine levels of pediatric cancer patients. AB - Secondary carnitine deficiency may occur in some diseases including malnutrition. The present study examined the serum carnitine levels of children with cancer and their relationship with nutritional status. Fifty-one (mean age: 104 +/- 23 months) patients with cancer were evaluated at diagnosis and 3 months after the initiation of the treatment. There were significant differences between the mean carnitine levels of patients before and during the treatment (p: .004). Although initial carnitine levels of patients were similar to those in control groups, there was a significant dif ference between the mean carnitine levels of patients and those of the control group at the third month (p: .02). The prevalence of malnutrition at the third month of the treatment (43%) was higher from the prevalence at diagnosis (33%) but this was not significant. No significant relationship was found between carnitine levels and nutritional status of patients either at diagnosis or during treatment. These results showed that inadequate intake of carnitine or its precursors could not be responsible for decrease in carnitine levels. Metabolic changes that result from therapy and/or from neoplastic process may be responsible for the decrease in carnitine levels. Detailed studies, including measurements of fractions of carnitine and urinary carnitine excretion according to individual drug, are necessary to determine real cause of this decrease. PMID- 11787864 TI - Overall and event-free survivals for acute lymphoblastic leukemia in children at a single institution in Taiwan. AB - The results of treatment for childhood acute lymphoblastic leukemia (ALL) have improved dramatically over the past three decades. The authors present the long term outcome of patients (n = 151) with ALL enrolled in 4 consecutive clinical trials conducted from 1982 to 1993 at Mackay Memorial Hospital. During this period, the backbone of the treatment remained relatively unchanged, including a 3- to 4-drug remission induction, central nervous system (CNS)-directed therapy, and cyclic pulses of vincristine and dexamethasone during maintenance therapy. More intensive therapy, consisting of reintensification and addition of more drugs during maintenance, was reserved for high-risk and very-high-risk patients. The overall survival and event-free survival (+/- 1 SE) were 70 +/- 4.1% and 64 +/- 4.3 %, respectively, with follow-up ranging from 7.6 to 18.7years (median 12.2 year). The isolated CNS relapse rate was 4.3%. The dropout rate significantaly decreased from 35% in 1982-1984 to 0% in 1991-1993. Although the patient population is small, the overall results for childhood ALL at the authors' hospital are encouraging as compared to earlier reports in Taiwan. PMID- 11787865 TI - Chronic hemolytic anemia associated with glucose 6-phosphate dehydrogenase (Guadalajara)1 159 C --> T (387 Arg --> Cys) deficiency associated with Gilbert syndrome in a Turkish patient. AB - The case of an 8-year-old male child with severe kernicterus sequelae is presented in this paper. The child's hemoglobin value varied between 6.0 and 10.8 g/dL and his reticulocyte count ranged between 3.4 and 46.0% during the steady state condition and hyperhemolytic crisis, respectively. A chronic hemolytic type of red cell G6PD deficiency was diagnosed. DNA studies indicate that the mutation was G6PD Guadalajara 1159 C --> T (387 Arg --> Cys) that is situated at the NADP binding site. Additionally, extra nucleotides of (TA) in the A(TA)n TAA motif of the promoter region of the uridine diphosphate-glucuronosyltransferase gene (UGT 1 A) were found to be homozygous in the patient. The coexistence of Gilbert syndrome with a chronic type of G6PD deficiency was suggested as a cause of neonatal hyperbilirubinemia leading to kernicterus. PMID- 11787866 TI - Childhood non-Hodgkin lymphoma presenting as hemophagocytic syndrome. AB - An 8-year-old girl with a progressive systemic hemopagocytic syndrome was found to have non-Hodgkin lymphoma (NHL) after multiple nondiagnostic biopsies. Routine histochemistry and flow cytometry demonstrated this to be a peripheral T-cell process and cytogenetics identified a t(2;5)(p23;q35). An extensive evaluation for an infectious agent failed to identify a pathogen. Treatment according to a standard lymphoma protocol produced a rapid response and the girl remains in remission without evidence of hemophagocytic syndrome 18 months from diagnosis. In children with systenic hemophagocytosis, a diagnosis of NHL should be aggressively pursued. PMID- 11787867 TI - Immunological status of thalassemia syndrome. AB - A major cause of morbidity and mortality in thalassemic patients is infections, assumed to be the result of immunological changes. In this study immune functions of peripheral blood lymphocytes have been studied in 38 beta-thalassemia major, 12 beta-thalassemia trait, and 17 healthy children. Results show decrease in CD4+/CD8+ ratios in the beta-thalassemia major group and no difference according to absolute T-lymphocyte numbers and activated T-cell numbers. These results do not correlate with the tendency to infection. No significant difference was found in humoral immunity. The study of other factors in thalassemia is needed to detect those who are more susceptible to infections. PMID- 11787868 TI - Recurrent arterial thrombosis in a child: primary antiphospholipid antibody syndrome. AB - Antiphospholipid antibody syndrome (APS) is characterized by the association of recurrent arterial or venous thrombosis or recurrent fetal wastage and the presence of circulating antiphospholipid antibodies, detected as anticardiolipin antibodies or lupus anticoagulant. The authors report an 8-year-old girl, who presented with central retinal artery occlusion and live do reticularis and was diagnosed as APS. Despite the proper anticoagulant treatment she had several cerebral ischemic events and died 29 months after the diagnosis. A larger number of pediatric case investigations will be required for better understanding and treating this rare thrombotic disorder. PMID- 11787869 TI - Thrombocytopenia and emperipolesis in a patient with hepatitis a infection. AB - lmmune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. A 13 year-old girl was admitted to a hospital with the epistaxis and purpura after an attack of jaundice 6 weeks before. The diagnosis of hepatitis A virus (HAV) induced thrombocytopenia was made. Furthermore, erythrophagocytosis by megakaryocytes was demonstrated in the bone marrow of the patient. Although hematologic complications following hepatitis B and C viruses are commonly reported, the association of hepatitis A virus and thrombocytopenia has rarely been described. PMID- 11787870 TI - Disseminated malignant ectomesenchymoma (MEM): case report and review of the literature. AB - Malignant ectomesenchymoma (MEM) is a rare soft tissue tumor believed to arise from a pluripotent migratory neural crest cell and composed fo both a mesenchymal element and a neuroectodermal element. The authors report the case of an 11-month old male who presented with a local abdominal MEM and systemic metastases into lungs, liver, bones, and bone marrow. This is the first reported case of an MEM with initial bone marrow dissemination. The tumor consisted of a neuroblastoma component and a mesenchymal component with sarcomatous features. Diagnosis and therapy were complicated by the histological heterogeneity of the tumor, which also influenced the clinical appearance and course in this case. A literature search revealed 15 other evaluated cases that arose in soft tissue and had adequate clinicopathologic data. Complete surgical resection was the mainstay of treatment, and chemotherapy also appeared to be important. In all reported patients (n = 3) with initial metastases or bone marrow dissemination, as in this case, no cure could be achieved. In patients with disseminated MEM, new therapeutic approaches such as high-dose chemotherapy followed by stem cell rescue should be considered, similar to the current strategy in patients with stage VI neuroblastoma or soft tissue sarcoma. PMID- 11787871 TI - Lupus patients are protected from cancer. PMID- 11787872 TI - Protein-losing enteropathy in a young African-American woman with abdominal pain, diarrhea and hydronephrosis. AB - The case of a 21-year-old African-American woman who presented with abdominal pain, diarrhea and hydronephrosis and who proved to have protein-losing enteropathy secondary to systemic lupus erythematosus is discussed. This is an unusual complication of lupus. PMID- 11787873 TI - Systemic lupus erythematosus and B-cell hematologic neoplasm. AB - The association of systemic lupus erythematosus (SLE) and B-cell malignancy is widely reported in the literature. Here we report nine cases of concurrent of SLE or discoid lupus erythematosus (DLE) and lymphoma or plasma cell disorder. A MEDLINE search was done using the keywords, 'SLE' and 'lymphoma' and the characteristics of all identified cases were summarized and analyzed, along with data from our own cases. Numerous variants of B-cell malignancies were encountered in these patients. B-cell malignancy occurs after the diagnosis and treatment of SLE in most reported cases, although it may precede SLE, or occur synchronously with it. The age at onset of the B-cell neoplasm in SLE patients is similar to that in the general population. Mortality in patients with both diseases is associated with progressive B-cell neoplasm, sepsis secondary to either disease, or both. B-cell malignancy and SLE seem to run independent clinical courses rather than being affected by each other. The use of immunosuppressive drugs is common in patients with SLE diagnosed prior to B-cell lymphoma, arguing that the effect of immunosuppression on the pathogenesis of lymphoma can not be excluded. Three areas worthy of study regarding the probable mechanisms for the occurrence of SLE and B-cell malignancies are discussed. A tumor suppressor gene PTEN may link the two disorders via a defective apoptosis pathway to eliminate hyperactive B and T cells in SLE. The accumulation of clonally expanded hyperactive B-cells that recognize self-antigens in the lymph nodes of SLE may predispose these B-cells to DNA breaks, facilitating tumorigenesis. Lastly, EBV infection, found to have a high prevalence in SLE patients, may serve as a common etiological factor in both disorders. PMID- 11787874 TI - Longitudinal myelitis associated with systemic lupus erythematosus: clinical features and magnetic resonance imaging of six cases. AB - Myelopathy is a rare central nervous system (CNS) complication associated with systemic lupus erythematosus (SLE). Acute transverse myelitis (ATM) is the most frequent form of SLE-related myelopathy. Magnetic resonance imaging (MRI) typically shows increased signal intensity in T2-weighted images and cord swelling. In the present paper, we describe six cases of SLE-related myelopathy with multiple increased signals in the T2-weighted images involving continuous levels of the cervical and thoracic spinal cord, a distinctive feature recently named 'longitudinal myelitis'. The clinical and laboratory findings are similar to those presented by ATM patients, including paraparesis, sensory level and sphincter disturbances. Four patients had positive antiphospholipid antibodies (aPL) suggesting that this could be a characteristic of longitudinal myelitis. Treatment in all cases included high doses of corticosteroids and immunosuppressive agents (intravenous (i.v.) cyclophosphamide). Anticoagulation therapy was given to one patient and two others received low doses of aspirin. The outcome was mainly unfavorable with slow improvement in only one case, no improvement in two and relapse of the myelopathy in the remaining three. In conclusion, longitudinal myelitis is an unusual form of SLE-related myelopathy, it might be associated with aPL and it has a poor prognosis. PMID- 11787875 TI - Dual binding capabilities of anti-double-stranded DNA antibodies and anti ribosomal phosphoprotein (P) antibodies. AB - The aim of this study is to identify distinctive properties of pathogenic anti double stranded DNA antibodies and anti-ribosomal P antibodies. The binding activity of anti-dsDNA and anti-ribosomal P antibodies to their cognate antigens in 0.15 M and 1.5 M NaCl solutions on ELISA was examined. All anti-dsDNA and anti ribosomal P antibodies exhibited a loss of their binding activity from 37.5 to 100% and from 2.3 to 97.4% in high ionic strength buffers, respectively. In contrast, anti-U1RNP antibodies and anti-Ro/SSA antibodies lost from 0 to 32.7% and from 0 to 40.1% of their binding activity, respectively. Anti-dsDNA and anti ribosomal P antibodies from patients with nephropathy showed significantly higher binding activity in high ionic strength buffers than those from patients without nephropathy. Study of paired sera from lupus nephritis patients revealed that anti-dsDNA and anti-ribosomal P antibodies from patients during disease flare show stronger binding activity in high ionic strength buffer than those during remission. Most anti-dsDNA and anti-ribosomal P antibodies bind their antigens by ionic interactions that are sensitive to high salt. Such dual binding capability of anti-dsDNA and anti-ribosomal P antibodies may underlie their multiple cross reactivities to various epitopes and help elucidate the pathogenic potential of autoantibody subsets. PMID- 11787877 TI - Anticardiolipin antibodies are not associated with rheumatic heart disease. AB - The aim of this study was to examine the prevalence of anticardiolipin antibodies in rheumatic valve heart disease. Serum samples of 31 consecutive patients with rheumatic heart disease and documented valve involvement, as well as six patients with acute rheumatic fever were tested for IgG anticardiolipin antibodies by a validated ELISA. No anticardiolipin antibodies were found when a cut-off point set at mean +/- 5 s.d. was applied. We can conclude that anticardiolipin antibodies are not present in rheumatic heart disease patients and, as suggested by several observations, these antibodies do not appear to have a pathogenic role in this particular disease. PMID- 11787876 TI - Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity. AB - Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fas-mediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4+, CD8+ and CD19+ lymphocytes of SLE patients with inactive (n = 20) and with active disease (n = 13). SLEDAI-scores were calculated. Healthy volunteers (n = 14) served as controls. Percentages of CD4+ T-cells expressing CD25 and CD19+ B-cells expressing CD38 were increased in patients with active disease compared to controls (P = 0.03, P = 0.04, respectively). In contrast to CD4+ and CD8+ cells, percentages of CD19+ cells expressing Fas were increased in SLE patients with active disease (P = 0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P = 0.006) and controls (P = 0.0007). Percentages of CD19+ cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptotic lymphocytes in SLE patients. PMID- 11787878 TI - Spontaneous rupture of the spleen: an unusual complication of systemic lupus erythematosus. AB - Although splenic abnormalities are widely recognised in patients with lupus, spontaneous rupture of the spleen is rare. We describe a patient whose spleen ruptured spontaneously 19 years after the onset of her disease, and compare this case with four others that have been described in the previous literature. Possible contributing factors to this rupture are discussed. PMID- 11787879 TI - Severe pulmonary hemorrhage as the initial manifestation in systemic lupus erythematosus with active nephritis. AB - Pulmonary hemorrhage (PH) is an uncommon clinical manifestation of patients with systemic lupus erythematosus (SLE). In this report, we describe a 14-year-old male with PH as the sole clinical manifestation of his SLE. Kidney biopsy was performed and the report revealed lupus nephritis class IVb. He demonstrated a rapid clinical response to the therapy of intravenous pulse methylprednisolone. Awareness of the possibility of PH as a sole clinical presentation of SLE may aid in the diagnosis and early aggressive management of this condition. PMID- 11787880 TI - Cat scratch disease (bartonellosis) mimicking an SLE flare. AB - Only recently Bartonella species have been recognized as important human pathogens. Cat scratch disease (CSD), caused by infection with Bartonella henselae, shows a steady increase in the number of cases throughout the world. We report a case of an 18-year-old woman with systemic lupus erythematosus (SLE) who presented with ongoing fever, arthralgias and loss of weight which did not respond to increasing doses of corticosteroids. After exclusion of common infections a photograph of her cat in combination with scratch marks on her arms finally led to the suspicion of CSD. This tentative diagnosis was confirmed serologically. Under clarithromycin treatment the patient rapidly responded and her temperature dropped within 2 days. PMID- 11787881 TI - Renal crisis in asclerodermic scleroderma--lupus overlap syndrome. AB - A 24-year-old woman with overlapping features of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly accelerating hypertension accompanied by neuropsychological deficits and tonic-clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway. PMID- 11787882 TI - Lupus in Singapore. PMID- 11787883 TI - European Working Party on Systemic Lupus Erythematosus: a 10 year report. PMID- 11787885 TI - Do we need an international consensus statement on classification criteria for the antiphospholipid syndrome in the paediatric population? PMID- 11787884 TI - Multiple thromboses in major arteries in a patient with antiphospholipid syndrome associated with excess of a large multimer of von Willebrand factor. PMID- 11787886 TI - The association of pure red cell aplasia with the antiphospholipid syndrome. PMID- 11787887 TI - Invited editorial: Welsh tritium. PMID- 11787888 TI - An overview of tritium behaviour in the Severn Estuary (UK). AB - Measurements of tritium (3H) activity in marine species in the Severn Estuary (UK) show concentrations significantly above those predicted by standard models. Concentration factors of 10(4) between seawater and marine species are observed; standard models assume a concentration factor of 1. In addition, the vast majority of activity is present in the form of organically bound tritium (OBT). The critical group dose from tritium--to consumers of local flounder--is estimated as approximately 36 microSv per annum. The measurements are related to the authorised release of wastes, via the sewer system, from the Amersham plc plant at Cardiff. The radiochemical plant manufactures a wide range of isotopically labelled compounds for use in life science research. The elevated levels of tritium observed in marine species have led to a programme of investigative work by specialist organisations. This paper describes the various definitions, measurements and significance of the term OBT. It also outlines the environmental observations and preliminary conclusions from the investigative programme to date. PMID- 11787889 TI - A survey of patient dose and image quality for computed tomography scanners in Wales. AB - The main aim of the study was to assess the current level of radiation dose from computed tomography scanning in the NHS in Wales and to compare these results with previous studies in Wales and the UK. In addition, the relationship between patient dose and image quality was investigated by comparing mean patient dose calculations with image noise using two quality assurance (QA) phantoms. The results show that although the introduction of spiral scanners has reduced the dose per examination, the collective dose per scanner has actually increased. The results also highlight the potential for relating dose and objective measures of image quality to assist in the selection of scanning parameters to optimise dose without compromising image quality. PMID- 11787890 TI - A tele-injector for large doses of radionuclides in diagnostics and therapy. AB - The risks and the inconveniences of the oral administration of radionuclides for therapeutic purposes are examined. A remotely operated injector which permits the direct injection of the radioactive dose from the sealed bottle to the vein of the patient to lower the exposure dose to the operator is illustrated. The tele injector can be also used each time a large dose of radioactive substance needs to be injected for diagnostic purposes, or if subdivision of the mother solution into other sterilised bottles is necessary. PMID- 11787891 TI - Modulation of radiation-induced protein kinase C activity by phenolics. AB - Natural phenolic compounds were tested in vitro for their effect on the activity of protein kinase C (PKC) isolated from the liver cytosol and the particulate fraction of unirradiated mice and mice irradiated at 5 Gy. Following irradiation, the PKC activity was found to be increased in both cytosolic and particulate fractions. Curcumin, ellagic acid and quercetin were effective in inhibiting radiation-induced PKC activity. Curcumin and ellagic acid were found to be more inhibitory towards radiation-induced PKC activity, while quercetin was the least effective. Curcumin was found to inhibit the activated cytosolic and particulate PKC at very low concentrations. Activation of PKC is one of the means of conferring radioresistance on a tumour cell. Suppression of PKC activity by phenolics may be one of the means of preventing the development of radioresistance following radiotherapy. PMID- 11787892 TI - Radiation dose to voluntary kidney donors during renal angiography procedures. AB - The radiation dose to voluntary kidney donors undergoing renal angiography performed using digital subtraction angiography (DSA) was estimated. The effective dose was calculated from values of dose-area product measured using a Diamentor dose-area product meter. The duration of the fluoroscopic screening and the number of image acquisitions during each examination varied depending upon the number of arteries supplying the kidneys and other parameters. The effective dose varied from 2.3 mSv to 30.5 mSv. The clinical aspects involved during the study were also taken into consideration in the analysis of the data. PMID- 11787893 TI - Logic and ethics in radiation protection. AB - The International Commission on Radiological Protection (ICRP) continues to accept the assumption of a linear non-threshold dose-response relationship (LNT) as the most likely one. In that case, basic logic as well as widely accepted ethics require that the full collective dose be used for detriment assessments and in procedures for optimisation of radiation protection. This means that even the smallest doses must be taken into account in the assessment of the global collective dose if they contribute significantly together. However, in calculating collective doses over time, some reasonable restriction of the integration period has to be employed, mainly because of the uncertainties involved in the assessment of future detriment. There are also uncertainties in the LNT assumption, but the precautionary principle would not permit that this is taken as an excuse for neglecting small doses. PMID- 11787894 TI - Radioiodine therapy: care of the helpless patient and handling of the radioactive corpse. AB - Nurses caring for a helpless patient following a nominal 800 MBq administration of radioiodine were concerned about their radiation dose. Using published data, a nurse could receive an estimated 650 microSv per shift. A regime to restrict their dose was planned using a 500 microSv dose constraint. Thermoluminescent dosimeters indicated a maximum whole-body effective dose of 250 microSv. Three days post 131I administration the patient died (estimated activity in the body 400 MBq). A minimum delay of two weeks was advised prior to a post-mortem. Special precautions were issued to minimise contamination. Dose rates (microSv h( 1)), measured one day after the patient died, at the level of the thyroid, chest and bladder at 0.01 m from the corpse were 1800, 290 and 73 respectively. At 1.0 m the dose rate was 26 microSv h(-1) at all levels. The pathologist was estimated to have received a maximum whole-body dose of 400 microSv during the post-mortem. Contamination measurements (Bq cm(-2)) made following the post-mortem were as follows: pathologist's hands 5, clothes 0, towels 1.8, saw 5, instruments 0.5, plastic sheet 0.8, scales 0.4 and floors/walls 1.1. These data indicate that with appropriate radiation protection guidelines, staff can be reassured that their doses in these circumstances are very low. PMID- 11787895 TI - Comments on 'Hereditary effects of radiation'. PMID- 11787896 TI - Study of health effects of low-level radiation in USA nuclear shipyard workers. PMID- 11787897 TI - Recent publications and research activities at the Radiation Effect Research Foundation. PMID- 11787898 TI - SRP Scientific Meeting: Dosimetry, Biology and Risks. October 2000. PMID- 11787899 TI - SRP Meeting: Social and Political Implications of Communicating Radiation Risk. Daresbury, Warrington, 20 June 2001. PMID- 11787900 TI - SRP Meeting: Visit to Hack Green Secret Nuclear Bunker. 20 June 2001. PMID- 11787901 TI - SRP Scientific Meeting: Recent Legislation--Achievements and Future Challenges. London, 9 October 2001. PMID- 11787902 TI - The Ionising Radiations Advisory Committee Open Meeting. 10 October 2001. PMID- 11787903 TI - The Academy of Medical Sciences Scientific Meeting: Radiation, Health and Chernobyl. London, 10 October 2001. PMID- 11787904 TI - The effect of bracing on proprioception of knees with anterior cruciate ligament injury. AB - This paper is a comprehensive review on the effect of bandaging, bracing, and neoprene sleeves on knee proprioception following anterior cruciate ligament (ACL) injury and reconstruction with a focus on studies that have measured joint position sense and threshold to detection of passive knee motion. Disruption of the ACL does not appear to alter joint position sense soon after injury, although there is evidence that in some subjects deterioration may occur over time. An ACL tear creates a deficit in the threshold to detection of passive knee motion soon after injury and in those with chronic tears. The magnitude of worsening is less then 1.0 degree of movement in flexion-extension and of questionable concern from a clinical and functional perspective. Application of a functional brace or neoprene sleeve to the ACL-deficient limb does not improve the threshold to detection of passive knee motion; however, application of an elastic bandage to a knee with an ACL tear improves joint position sense. Reconstruction of a torn ACL is associated with a deficit in the threshold to detection of passive knee motion, and during the first year of healing the use of a neoprene sleeve provides improvement. Two years following ACL reconstruction there is no deficit in the threshold to detection of passive knee motion and the use of a brace has no effect on this outcome. PMID- 11787905 TI - The relationship between self-reported and clinical measures and the number of days to return to sport following acute lateral ankle sprains. AB - STUDY DESIGN: This is a prospective observational study. OBJECTIVE: To determine the relationship of self-reported and clinical measures to the number of days to return to sport following acute lateral ankle sprains. BACKGROUND: In order to direct rehabilitation, injury classification schemes should include self-reported and clinical measures that help prognosticate the number of days to return to sport (DAYS). METHODS AND MEASURES: Twenty Division II college athletes (7 men, 13 women; mean age = 19.2 +/- 1.1 years) were assessed following an acute lateral ankle sprain and upon return to sport. Athletes were assessed by three self reported measures: global function question, Short Form-36 Physical Function scale (SF36PF), visual analog pain scale, and four clinical measures: ankle active range of motion (AROM), ankle dorsiflexion strength, ankle plantar flexion strength, ambulation status. Simple regression, multiple regression, and effect sizes (ES) were used to analyze these data. RESULTS: The simple regression revealed a statistically significant relationship between DAYS and the global function question (r2 = .22), the SF36PF (r2 = .28), and the patient's ambulation status (r2 = .27). A multiple regression using these three variables in combination was also statistically significant (P = .015) and explained approximately one-third of the variance in DAYS, (r2 = .37). All dependent variables revealed large or moderate ES. CONCLUSION: Self-reported functional measures in conjunction with the athlete's ambulation status are important factors in predicting the number of days to return to sport following acute lateral ankle sprains. Further research using large sample sizes and other clinical and functional measures is necessary. PMID- 11787906 TI - The effects of patellar taping on knee kinetics, kinematics, and vastus lateralis muscle activity during stair ambulation in individuals with patellofemoral pain. AB - STUDY DESIGN: Pre- and postintervention repeated measures design. OBJECTIVE: To determine the effects of patellar taping on knee kinetics, kinematics, and vastus lateralis muscle activity during stair ambulation in individuals with patellofemoral pain (PFP). BACKGROUND: Patellar taping is a common treatment technique for individuals with PFP. Specific data on whether patellar taping improves gait variables, however, are limited. METHODS AND MEASURES: Ten subjects with a diagnosis of PFP were studied (five men, five women). The subjects' mean age, height, and mass were 36.5 +/- 11.1 years, 173.1 +/- 10.3 cm, and 70.9 +/- 13.3 kg, respectively. Lower extremity kinematics, ground reaction forces, and vastus lateralis EMG were obtained simultaneously while subjects ascended and descended stairs, under taped and untaped conditions. Knee moments were calculated using inverse dynamics equations. Four 2 x 2 (tape condition x stair condition) ANOVAs for repeated measures were generated for cadence and average stance phase knee extensor moment, knee flexion angle, and EMG. RESULTS: On the average, a 92.6% reduction in pain was observed following the application of tape. Increases in cadence, knee flexion angles, and knee extensor moments were observed under the taped condition for both stair ascent and descent; however, no difference in average vastus lateralis EMG was found. CONCLUSIONS: Although patellar taping resulted in decreased pain and increased knee extensor moments, knee flexion angles, and cadence during stair ambulation, the vastus lateralis EMG activity level did not change with taping. Based on data from the vastus lateralis, care must be taken if improved gait parameters indicate change in muscle recruitment. PMID- 11787907 TI - The safety and effectiveness of a new hysteroscopic method for permanent birth control: results of the first Essure pbc clinical study. AB - BACKGROUND: Current methods of female surgical sterilisation require incisional surgery, general anaesthesia and a prolonged recovery time. We studied the safety and effectiveness of Essure pbc, a minimally invasive, transcervically placed micro-insert that occludes the Fallopian tubes, resulting in permanent female contraception. Device under study: The Essure pbc implant is a dynamically expanding micro-insert which is placed in the proximal section of the Fallopian tube using a modified minimal access technology for cannulating the tube. STUDY POPULATION: Women aged 21-43 seeking permanent birth control. METHODOLOGY: Essure pbc micro-inserts were inserted into the proximal portion of the Fallopian tubes under hysteroscopic visualisation with intravenous sedation or paracervical block. RESULTS: Bilateral device placement was achieved in 111 of 130 (85%) women who underwent device placement attempts. Women found the device placement procedure to be highly acceptable. Of women wearing the device for up to two years rate, 97% rated it to be very good to excellent. There have been no pregnancies reported in 1894 woman-months of effectiveness. Adverse events preventing women from relying on Essure pbc were < 5%. DISCUSSION: This first clinical trial showed the Essure pbc method of permanent contraception to be safe and highly acceptable to women. Experience and improvements to the delivery system should increase overall micro-insert placement rates. CONCLUSION: The Essure pbc method of permanent contraception is an exciting alternative to vasectomy or laparoscopic sterilisation that does not require general anaesthesia or incisions. PMID- 11787908 TI - A portable, disposable device for patient-controlled epidural analgesia following Caesarean section: evaluation by patients and nurses. AB - Twenty patients undergoing elective Caesarean section were provided with a pethidine-primed disposable Go Medical epidural infuser for postoperative pain control. Patients and nurses evaluated the device by completing a questionnaire. The infuser delivered adequate analgesia, was easy to understand and use, provided the patients with control over their pain relief and allowed good mobility The nursing staff found the device easy to prime and understand, the only drawback being the occasional incidence of equipment failure. The patients expressed a high level of satisfaction with the device and all would use it again if offered the chance. We conclude that the Go Medical epidural infuser is a safe and effective device as used in the postnatal ward setting. PMID- 11787909 TI - A randomised controlled trial comparing a dilating vaginal speculum with a conventional bivalve speculum. AB - Cervical smears are traditionally taken with the aid of a metal or disposable plastic bivalve speculum. Many women complain of discomfort with these specula. This study compares the efficacy and women's experiences of a new 'dilating speculum' called the Veda-scope, with a conventional metal bivalve speculum (Pederson). The aims of this study were: to determine whether the Veda-scope provides adequate visualisation of the cervix and vaginal walls and an adequate cervical cytology specimen; and to compare user acceptability and women's levels of comfort between the Veda-scope and the bivalve speculum. Sixty-four women were randomised to be examined with the Veda-scope and 60 with the bivalve speculum, by one of two operators. Each woman completed a questionnaire that included subjective views of their previous cervical smear experiences, and acceptability of the examination at the study consultation. Cytologists were blinded as to which speculum was used for cervical sampling. Of women examined, 7-83% of women found Veda-scope examinations comfortable, compared to 38-62% of women who found examinations with the bivalve comfortable; 94% of the women preferred the 'comfort' of the Veda-scope. The Veda-scope was as good as the bivalve speculum in providing samples for cytological analysis following the initial learning curve, and also provided markedly superior magnified views of the cervix and vaginal fornices. PMID- 11787910 TI - A systematic review of pregnancy outcome following preterm premature rupture of membranes at a previable gestational age. AB - Our objective was to identify the maternal and fetal outcome following preterm premature rupture of membranes at a previable gestational age (less than 23 weeks). We conducted a systematic review to identify articles that assessed perinatal and maternal outcome of pregnancies complicated by preterm premature rupture of membranes in early weeks of gestation. Articles available in the electronic database (MEDLINE and EMBASE) from the year 1980 to 1999 were included in the review The subjects were patients with rupture of membranes less than 23 weeks of gestation. Two reviewers independently reviewed the abstracts and finally 11 articles were eligible. Data were extracted separately from available sources within the articles. Data on individual subjects were extracted in eight studies whereas in three studies it was only possible to extract the data on divided gestational age groups. We found a live birth rate of 67% (95% CI: 60-73) in these groups of patients. The perinatal survival was 18% (95 % CI: 11-28) and 17% (95% CI: 16-27) in less than 20 weeks and 20-23 weeks groups respectively. Very little information could be extracted regarding perinatal morbidity Respiratory distress syndrome was diagnosed to be the major morbidity among the surviving infants. The review illustrates how little good quality information is available for pregnancy outcome following PPROM at less than 23 weeks gestation. Although the survival prognosis of this group of patients is poor, the perinatal survival is approximately 21%. PMID- 11787911 TI - Introducing external cephalic version to clinical practice. AB - A service offering external cephalic version to all women with breech presentations at 36-38 weeks' gestation was introduced at St George Hospital in July 1997. This paper describes how this service was established and reports the clinical outcomes over the first three years; 116 external cephalic versions (ECV) were attempted on 114 women and success was achieved in 58 women (51%). Of the 58 women, 43 (74%) subsequently had vaginal deliveries. There were no fetal deaths, immediate Caesarean sections, or placental abruptions as a result of the ECV procedure. There were two (2%) episodes of transient fetal bradycardia following ECV, both of which returned to normal with a subsequent normal neonatal outcome. Pre- and post-ECV Kleihauer levels were collected with no increase in levels as a result of the ECV ECV is a procedure that can, and should, be provided as part of a public hospital service. PMID- 11787912 TI - Carrying their own medical records: the perspective of pregnant women. AB - Freedom of information, access to and ownership of medical records are current and controversial issues in Australia. Relating to pregnancy and birth the debate provokes emotional responses and raises important questions about access to information, decision-making, responsibility, power and control. The aim of this qualitative study was to explore the impact on pregnant women of carrying their medical records throughout pregnancy Twenty-one women participated in face-to face individual interviews, which were coded for thematic analysis. The study found the reaction of women toward carrying their own records to be overwhelmingly positive. Maternal record holding had the potential to improve the level of communication between the health care worker and the pregnant woman and provided a greater sense of sharing and communication within the family The study also established that maternal record holding was of benefit to the woman's partner who was better informed and more involved in the pregnancy All but one of the women who participated favoured carrying their records in subsequent pregnancies. A concern about the potential for losing or misplacing records was not seen in this study, as no women lost their records. A sense of ownership would argue against this possible drawback. PMID- 11787913 TI - A protocol of selective antibiotic prophylaxis for caesarean section based on risk factors. AB - The aim of the study was to identify risk factors associated with increased risks of post Caesarean febrile morbidity from a retrospective epidemiological analysis, and to prospectively evaluate a protocol of selective antibiotic prophylaxis based on these risk factors. Caesarean section births over a three year period--during which no antibiotic prophylaxis protocol was practised--were reviewed. Risk factors for febrile morbidity were identified using both univariate and multivariate analysis. A protocol of selective antibiotic prophylaxis, incorporating the significant risk factors identified, was then evaluated prospectively over a nine-month period. The incidence of febrile morbidity from the retrospective study was 16.9%. A logistic regression model, with febrile morbidity as the dependent variable, identified only the duration of labour over 10 hours as a significant factor. A protocol of antibiotic prophylaxis using intravenous ampicillin was then practised in the presence of these two factors. Evaluation of this protocol after nine months showed that the incidence of febrile morbidity was reduced significantly from 20% in those not given antibiotics to around 9.6% in those eligible for and given antibiotics. However, the overall incidence of febrile morbidity remained at around 16-18%. PMID- 11787914 TI - A randomised trial of oral versus vaginal administration of misoprostol for the purpose of mid-trimester termination of pregnancy. AB - A prospective randomised controlled trial was undertaken to compare the efficacy of two routes of administration, oral versus vaginal, of the prostaglandin E1 analogue misoprostol (Cytotec) to effect termination of pregnancy in the mid trimester. Fifty-five women were recruited into the trial; 26 to receive all doses orally and 29 via the vaginal route. The dosing regimen was 400 microg as the initial dose followed by a second dose of 200 microg two hours later and then four-hourly 200 microg doses until delivery or 32 hours from commencement of treatment. If delivery had not been effected by the last dose of misoprostol, a Syntocinon infusion was started synchronously Misoprostol administered vaginally was significantly more effective than when administered orally as judged by induction-to-delivery interval and also the need or otherwise to augment therapy with a Syntocinon infusion. The average induction-to-delivery interval was 17.5 hours in the vaginal group compared to 33 hours in the oral group (p = 0.0003). The percentages of women who delivered at 24 and 48 hours were 93% and 100% in the vaginal administration group and 19% and 70% in the oral administration group (p < 0.05). No significant differences in complication rates or side effects were noted between the two groups PMID- 11787915 TI - Active management of the third stage at caesarean section: a randomised controlled trial of misoprostol versus syntocinon. AB - The objective of this trial was to investigate whether 500 microg oral misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss. Forty women undergoing elective or emergency Caesarean section were included in a placebo controlled randomised trial. Group 1 received oral misoprostol and a placebo intravenous bolus and Group 2 received intravenous Syntocinon and oral placebo tablets. The main outcome measures were estimated blood loss at Caesarean section, drop in serum haemoglobin, and the need for additional uterotonic agents. We found that there was no significant difference (p = 0.75) in estimated blood loss between the two groups. No differences were observed in the decrease in haemoglobin, requirement for additional oxytocics, the need for blood transfusion or the degree of shivering in each group (p > 0.05 in each case). We concluded that oral misoprostol could be used as an alternative oxytocic agent for the third stage at Caesarean section. However, there is an obvious need for a larger randomised controlled trial to be undertaken. Previous published studies have concentrated on vaginal births and further studies should be extended to Caesarean deliveries. PMID- 11787916 TI - The profile of substance-using pregnant mothers and their newborns at a regional rural hospital in New South Wales. AB - We conducted an audit study of identified substance-using mothers and their neonates at Lismore Base Hospital in the Northern Rivers region of New South Wales between January 1995 and December 1999. Women using marijuana and/or alcohol only were excluded. The average number of total births during the study period was 1,363 per year. Forty-nine mothers were identified as substance users with an incidence of seven per 1,000 total births. Twenty-three (47%) were methadone users, 14 (29%) methadone and intravenous heroin users, 11 (22%) heroin users, and one (2%) used amphetamines. Twenty-seven (55%) had irregular antenatal visits. Forty-one (89%) were hepatitis C positive. Forty-seven neonates were live born and there were two stillbirths. Thirty-seven (79%) required admission to the special care nursery, 40% of them for withdrawal alone. Twenty-seven (55%) babies had neonatal withdrawal and 23 (49%) required medication for withdrawal. The incidence of substance abuse among the pregnant women in this region is ten times higher than the previously quoted figures in metropolitan areas of Australia. PMID- 11787917 TI - Petrol sniffing in a pregnant Aboriginal population: a review of maternal and neonatal outcomes. AB - The study's aim was to determine if petrol sniffing during pregnancy is associated with adverse maternal and neonatal outcomes at the Alice Springs Hospital. The study design was a retrospective case note review. The subjects were Aboriginal women who delivered at the Alice Springs Hospital between July 1991 and September 1999 where petrol sniffing was identified on the discharge coding; 14 women with 21 pregnancies were identified. One hundred and eleven nulliparous Aboriginal women who delivered at hospital between July 1998 and June 1999, with singleton gestation in cephalic presentation, were identified from the birth register and used as the control group. We found that women identified as petrol sniffers during pregnancy presented later for antenatal care, had fewer antenatal visits, lower booking haemoglobin and weighed less at booking when compared with non-petrol-sniffing women. Women who sniffed petrol during pregnancy were more likely to have one or more sexually transmitted diseases identified during the pregnancy; to use other substances during pregnancy; to be colonised with group B Streptococcus; to have meconium stained liquor prior to delivery; and to have a still-birth. Infants born to petrol-sniffing mothers were more likely to have birthweight less than 2,500 g; to have Apgar scores of less than 7 at 5 minutes; to require admission to the neonatal unit; and to be placed in foster care or for adoption. We concluded that the pregnancy complicated by petrol sniffing should be recognised as one at increased risk of adverse outcome, necessitating increased antenatal surveillance. However, as with other substances abused, it is extremely difficult to determine the role played by the substance per se, and that of the lifestyle associated with the abuse behaviour. PMID- 11787918 TI - Obstetric and neonatal outcomes associated with maternal naltrexone exposure. AB - Poor maternal and neonatal outcomes are associated with the pregnant heroin user. These include increased antepartum haemorrhage, decreased neonatal birthweight and increased neonatal mortality Medically supervised withdrawal from heroin during pregnancy has, however, been discouraged due to possible risk to the fetus and because of the high incidence of return to regular illicit heroin use by the mother. In recent years, however, a number of withdrawal procedures using anaesthesia, oral sedation, or intravenous sedation, precipitated by naloxone and/or naltrexone have been developed and carried out successfully on pregnant heroin users. We have now collated information on 18 cases (19 detoxifications) from three countries (Portugal, Australia and the United Kingdom). These case study data, although limited, indicate that detoxification of the pregnant heroin user is possible without significant risk to the neonate or mother, with many women not returning to dependent heroin use following detoxification. Naltrexone maintenance has also been used in the non-pregnant heroin user to discourage illicit heroin use. Similarly to methadone, stabilisation on naltrexone may be associated with conception and pregnancy Over the past three years, 26 women have conceived while on the Western Australia naltrexone program. Due to the unknown teratogenic effects, most have ceased naltrexone intake at approximately seven or eight weeks gestation. In a number of instances, however, naltrexone maintenance has been recommenced following return to a dependent pattern of heroin use. As a consequence, neonates have had different periods of naltrexone exposure, building from the initial seven or eight weeks. We now report on seven women who have delivered and three who are well into their third trimester. Neonatal and obstetric features were unremarkable with good Apgar scores, birthweight and head circumference observed. In the three cases still in third-term gestation, normal fetal development has been observed at recent ultrasound examinations. These case data indicate that naltrexone maintenance may have a role in the management of the pregnant heroin user. PMID- 11787919 TI - Sonographic estimation of fetal weight in macrosomic fetuses: diabetic versus non diabetic pregnancies. AB - The objective of this study is to compare the accuracy of sonographic estimation of fetal weight of macrosomic babies in diabetic vs non-diabetic pregnancies. All babies weighing 4,000 g or more at birth, and who had ultrasound scans performed within one week of delivery were included in this retrospective study Pregnancies with diabetes mellitus were compared to those without diabetes mellitus. The mean simple error (actual birthweight--estimated fetal weight); mean standardised absolute error (absolute value of simple error (g)/actual birthweight (kg)); and the percentage of estimated birthweight falling within 15% of the actual birthweight between the two groups were compared. There were 9,516 deliveries during the study period. Of this total 1,211 (12.7%) babies weighed 4,000 g or more. A total of 56 non-diabetic pregnancies and 19 diabetic pregnancies were compared. The average sonographic estimation of fetal weight in diabetic pregnancies was 8% less than the actual birthweight, compared to 0.2% in the non diabetic group (p < 0.01). The estimated fetal weight was within 15% of the birthweight in 74% of the diabetic pregnancies, compared to 93% of the non diabetic pregnancies (p < 0.05). In the diabetic group, 26.3 % of the birthweights were underestimated by more than 15 %, compared to 5.4% in the non diabetic group (p < 0.05). In conclusion, the prediction accuracy of fetal weight estimation using standard formulae in macrosomic fetuses is significantly worse in diabetic pregnancies compared to non-diabetic pregnancies. When sonographic fetal weight estimation is used to influence the mode of delivery for diabetic women, a more conservative cut-off needs to be considered. PMID- 11787920 TI - Saline infusion sonohysterogram as initial investigation of the endometrium and uterine cavity. AB - The results of 54 consecutive saline infusion sonohysterograms (SIS) are presented. Sonohysterogram, in conjunction with Pipelle endometrial sampling, was found to be a reliable and accurate method of initial investigation of the endometrium and uterine cavity with good correlation with other methods of investigation. It was well tolerated in an outpatient setting, saved two out of three of the women from needing a hysteroscopy and curettage, and yielded information beyond that available from hysteroscopy and curettage. PMID- 11787921 TI - Trends in the incidence of ectopic pregnancy in New South Wales between 1990 1998. AB - During the last three decades, ectopic pregnancy rates have increased considerably in different parts of the world including Australia. Recent reports, however, suggest that the incidence is decreasing or at least stabilising. An analysis of the New South Wales Inpatient Statistics Data collected during the period between 1990 and 1998 has shown a decline in the rate of ectopic pregnancy after 1993. Overall the rate decreased from 17.4 per 1,000 births in 1990-1991 to 16.2 per 1,000 births in 1997-1998. The decline was greater for women aged 35-44 years than for younger women. The findings are consistent with recent studies in other countries, which indicate slowing or the end of the previous upward trend in the incidence of ectopic pregnancy PMID- 11787922 TI - Transfusion rate associated with hysterectomy for benign disease. AB - The transfusion rate associated with hysterectomy for benign disease is an indirect indicator of haemorrhage. It is used in quality assurance activities and is one measure of standard of care. This retrospective study was conducted to determine the transfusion rate for these operations in a tertiary referral hospital. In addition, it was considered that the information could be used in deciding the need for a routine preoperative group and save policy (G and S). The Blood Bank records of all women undergoing hysterectomy for benign disease from 1993-1998 were examined and the number of women transfused was recorded. A total of 1220 hysterectomies were performed. Of women having vaginal hysterectomies only 0.38% required transfusion compared with 2.18% for abdominal hysterectomies. These data suggest that there is no need for a strict policy of preoperative G and S for all patients. In addition, this information can be used as a benchmark when reviewing morbidity associated with hysterectomy and in particular when various methods of hysterectomy are compared. PMID- 11787923 TI - Symptoms and HPV infection of the vulva: clinical manifestations or mere coincidence? AB - Two hundred women with abnormal Pap smears and/or vulvar symptoms and 30 with normal Pap smears were investigated to determine the association between symptoms and (i) human papilloma virus infection of the vulva, and (ii) a spongiotic tissue reaction or a spongiotic dermatitis of the vulva. All had vulvar colposcopy and biopsy Human papilloma virus infection was diagnosed by histopathology and in situ hybridisation technique. HPV infection was present in biopsies of 48% of asymptomatic women and 33% with symptoms (p = 0.13) and HPV DNA in 37% of asymptomatic women and 31% with symptoms (p = 0.72). Spongiotic tissue reaction was diagnosed in 53.5% of asymptomatic women compared to 74% of symptomatic women (p = 0.007). This study suggests that vulvar symptoms are not clinical manifestations of HPV infection, but may be caused by dermatitis rather than HPV infection per se. PMID- 11787924 TI - Continuous versus cyclical transdermal oestrogen replacement therapy in postmenopausal women: effects on lipoprotein(a) and nitric oxide levels. AB - The purpose of our study was to compare the effects of cyclical versus continuous transdermal oestrogen replacement therapy on lipoprotein (a) (Lp(a)) and nitric oxide levels. The patients were randomly assigned into two groups. The first group received transdermal 17-beta oestradiol 50 microg/day for 21 days and the second group the same treatment on a continuous basis. Medroxyprogesterone acetate (10 mg/day orally) was added between the 14th and 25th days to each group. Lipoprotein (a) and nitric oxide levels were measured before the study and after six months. These values were compared using the Wilcoxon rank test within the groups and the unpaired t-test between the groups. Lipoprotein (a) levels decreased significantly in each group at the sixth month (p < 0.05). When compared between the groups, the decrease of lipoprotein (a) levels in the second group was more prominent at the sixth month (p < 0.05). Nitric oxide levels increased in each group after six months (p < 0.05). No difference in nitric oxide levels was observed between the groups before and after the therapy (p > 0.05). Continuous transdermal estradiol had a better effect on lipoprotein (a) levels than cyclical therapy The seven day pause in the 21-day administration did not affect nitric oxide levels negatively after six months. PMID- 11787925 TI - The young 'elderly' primipara revisited. AB - A 1970 analysis of labour ward data to determine whether primiparas in the 30 to 34 year age group should be considered 'at risk' due to age was repeated in 1997. Control groups were primiparas aged 20 to 23 and multiparas 2 and 3. Incidence of operative delivery, several other obstetric outcomes and the condition of the infant at birth were compared in various age groups. Both studies showed that the 30 to 34 age group was at increased risk of operative delivery PMID- 11787926 TI - Wernicke's encephalopathy due to hyperemesis gravidarum: an under-recognised condition. AB - We present a case of a 25-year-old woman with drowsiness, nystagmus, severe ataxia and areflexia, which developed six weeks after admission to an obstetric clinic for hyperemesis gravidarum. She had been treated with intravenous dextrose and electrolyte solutions and antiemetics. Magnetic resonance imaging (MRI) performed on the fifth day of her neurologic symptoms showed increased intensity in both thalami, periaqueductal grey matter, the floor of the fourth ventricle and superior cerebellar vermis in T2 weighted and FLAIR images. Clinical signs and MRI findings were consistent with the diagnosis of Wernicke's encephalopathy. On the third day of thiamine replacement, neurologic signs improved dramatically In addition to our case, we review 29 previously reported cases of Wernicke's encephalopathy associated with hyperemesis gravidarum, and emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy especially if they are given intravenous or parenteral nutrition. PMID- 11787927 TI - Neonatal pneumococcal sepsis in association with fatal maternal pneumococcal sepsis. AB - A live male infant was born at 37 weeks' gestation after a normal pregnancy to a 34-year-old mother. The baby developed bacteraemia with Streptococcus pneumoniae and recovered completely following treatment with antibiotics. The mother simultaneously developed bacteraemia with the same organism and died from septic shock. Blood culture isolates from mother and child were both serogroup 23F, and were shown to be identical by DNA fingerprinting. The literature reports rare cases of vaginal carriage and/or endometritis with this organism resulting in neonatal sepsis. Transmission to the neonate may have been ascending or haematogenous. A postmortem examination was refused. PMID- 11787928 TI - An uncommon cause of a destructive vulval lesion. AB - We present a case of a 39-year-old woman with a vulval lesion, which macroscopically looked consistent with a fungating squamous cell carcinoma of the vulva. However, further investigations demonstrated a less common cause for this presentation. PMID- 11787929 TI - Postpartum diagnosis of a maternal diaphragmatic hernia. PMID- 11787930 TI - Pregnancy after fontan repair of complex congenital heart disease. AB - We describe four successful pregnancies in three women who had previously had a Fontan repair for congenital heart disease. Each pregnancy resulted in a live birth and there was no maternal mortality The infants were premature, being delivered at 26, 30 and 35 weeks, and weighing 1,020, 1,333 and 1,930 g respectively The fourth infant was born at 32 weeks and no birthweight is available. Maternal complications occurred and were those anticipated after a Fontan repair. Two mothers required treatment for supraventricular arrhythmias (atrial flutter and fibrillation). Ventricular failure was present in two mothers and required ongoing drug treatment. Raised systemic venous pressures caused peripheral oedema in two mothers and hepatomegaly and ascites in one mother. The physiology, potential complications, anaesthetic concerns and drug treatment in pregnancy after Fontan repair are discussed. PMID- 11787931 TI - Angiomyofibroblastoma of the vulva. PMID- 11787932 TI - Prophylactic granulocyte colony-stimulating factor treatment for acquired chronic severe neutropenia in pregnancy. PMID- 11787933 TI - Rare major maternal complications after second trimester amniocentesis: sequelae of avoiding a transplacental approach. PMID- 11787934 TI - Re: glyceryl trinitrate (GTN) patches are unsuitable in hypertensive pregnancy. PMID- 11787935 TI - Relationship between birthweight and repeated courses of antenatal corticosteroids. PMID- 11787936 TI - Comparative morbidity figures for vaginal and abdominal hysterectomies. PMID- 11787937 TI - Postpartum haemorrhage is the leading cause of maternal death in developing countries. PMID- 11787938 TI - Human gastrinoma cells express calcium-sensing receptor. AB - The intravenous calcium injection test has been reported to be useful for the diagnosis of gastrinoma. However, the mechanism underlying calcium-evoked gastrin release is not fully understood. We investigated the mechanism of calcium stimulated gastrin release from gastrinoma cells in vitro with a particular focus on the calcium-sensing receptor (CaR). Human gastrinoma cells were taken from mechanically minced gastrinoma tissues obtained at surgery. In the perifusion system, high [Ca2+]o induced gastrin release from gastrinoma cells. As [Ca2+]o increased, [Ca2+]i rapidly increased, as monitored by fluorometry. The response was not inhibited by nifedipine, a blocker of the voltage-dependent calcium channel. Reverse transcriptase-polymerase chain reaction and subsequent Southern blot hybridization revealed the presence of the CaR gene in human gastrinoma tissues. Moreover, the expression of CaR in gastrinoma tissues was confirmed by immunohistochemistry. Our results demonstrated that CaR was expressed in human gastrinoma cells and could be involved in the mechanism of calcium-evoked gastrin release. PMID- 11787939 TI - Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. AB - Niemann-Pick type C (NPC) is a neurodegenerative disorder characterized by greatly altered somatic cholesterol metabolism. The NPC1 gene has recently been cloned and shown to have sequence homology to other sterol-sensing proteins. We have used a mouse model with a disrupted npc1 gene to study the effects of the cholesterol-mobilizing compound, 2-hydroxypropyl-beta-cyclodextrins (HPBCD), on the clinical course of this disorder. Treatment with two HPBCDs, with varying levels of 2-hydroxypropyl substitution, had effects in delaying neurological symptoms and in decreasing liver cholesterol storage while a third HPBCD was without effect. The ameliorating effect was not improved by longer exposure times (commencement of exposure in utero), however, it is not known if there is transplacental transfer of HPBCDs. The combination of HPBCD with probucol or nifedipine (which have previously been shown to lower liver cholesterol in this animal model) markedly decreased liver storage of unesterified cholesterol without altering the depressed levels of esterified cholesterol. The slight effects of the HPBCDs on neurological symptoms may be partially due to their apparent non-permeation of the blood-brain barrier (BBB). This non-permeation was assayed with radioactive tracers and was also present in the mdr1a knockout mice which have greatly increased BBB permeability for many drugs. Intrathecal delivery of HPBCD by an Alzet osmotic minipump did not improve its efficacy in ameliorating neurological symptoms. PMID- 11787940 TI - Calcium handling and sarcoplasmic-reticular protein functions during heart failure transition in ventricular myocardium from rats with hypertension. AB - The objective of this study was to determine the primary event that occurs in Ca2+-regulatory sarcoplasmic-reticular (SR) proteins during subacute transition from concentric/mechanically-compensated left ventricular (LV) hypertrophy to eccentric/decompensated hypertrophy. Using Dahl salt-sensitive rats with hypertension, changes of myocardial contraction, intracellular Ca2+ transients, SR Ca2+ uptake, protein levels of SR Ca2+ ATPase (SERCA2), phospholamban, and calsequestrin (CSQ), and mRNA levels of SERCA2 and CSQ were serially determined and compared between the established stage of LV hypertrophy (LVH) and the subsequent stage of overt LV dysfunction (CHF). In LVH, isolated LV papillary muscle preparations showed an equal peak-tension level and a mild prolongation of the isometric tension decay compared to those of age-matched controls. The Ca2+ transients as measured by aequorin were unchanged. The Ca2+ uptake of isolated SR vesicles and the protein/mRNA levels of SR proteins were also equivalent to those of the controls. In contrast, in CHF, the failing myocardium showed a further prolongation of the contraction time course and a 39% reduction of the peak tension development. The Ca2+ transients showed changes consisting of a decrease in the peak level and a prolongation of the time course. In addition, the SR Ca2+ uptake was decreased by 41%. Despite these functional changes, the protein and mRNA levels of the SR components remained equivalent to those of the age-matched controls. Thus, in this hypertensive animal, 1) at the LVH stage, myocardial contractility and intracellular capability to regulate Ca2+ remained normal; 2) at the CHF stage, impaired SR Ca2+ handling and the subsequent reduction of myocardial contraction were in progress; and 3) impairments of SR function occurred at the post-translational protein level rather than at the transcriptional/translational levels. Our findings support the role of SR proteins as the primary determinant of the contractile dysfunction that occurs during the heart-failure transition; however, post-translational modulators of these SR elements may also be critical. PMID- 11787942 TI - Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry. AB - Recent studies show that angiotensin II (AngII) can act from within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane AngII receptors. The role of this intracellular AngII (AngIIi) is unclear. Besides direct effects of AngIIi on cellular processes one could hypothesise a possible role of AngIIi in modulation of cellular responses induced after heterologous receptor stimulation. We therefore examined if AngIIi influences [Ca+]i in A7r5 smooth muscle cells after serotonin (5HT) or UTP receptor stimulation. Application of AngIIi using liposomes, markedly inhibited 45Ca2+ influx after receptor stimulation with 5HT or UTP. This inhibition was reversible by intracellular administration of the AT1-antagonist losartan and not influenced by the AT2-antagonist PD123319. Similar results were obtained in single cell [Ca2+]i measurements, showing that AngIIi predominantly influences Ca2+ influx and not Ca2+ release via AT1-like receptors. It is concluded that AngIIi modulates signal transduction activated by heterologous receptor stimulation. PMID- 11787941 TI - Additional evidence for the anti-inflammatory and anti-allergic properties of the sesquiterpene polygodial. AB - This study evaluates further the anti-inflammatory and anti-allergic properties of polygodial, a sesquiterpene extracted from the barks plant Drymis winteri (Winteraceae). Polygodial (12.8-128.1 micromol/kg, i.p.) 30 min prior, inhibited significantly the mouse paw oedema induced by prostaglandin E2, bradykinin (BK) substance P (SP), dextran, platelet activating factor (PAF) or carrageenan. Polygodial also inhibited arachidonic acid-, capsaicin- and croton oil-induced ear oedema in mice. Polygodial (42.7 micromol/kg, i.p.), significantly inhibited both exudation and cell influx when assessed in the pleurisy induced by SP and histamine, and to a less extent the inflammatory response caused by carrageenan, PAF, BK and des-Arg9-BK. Finally, polygodial (4.2-42.7 micromol/kg, i.p.) produced dose-related inhibition of paw oedema induced by ovalbumin, protecting in a time-dependent manner the anaphylactic shock induced by endovenous administration of ovalbumin in animals which had been actively sensitised by this antigen. These and our previous results indicate that the major component present in the bark of the plant D. winteri, the sesquiterpene polygodial exerts an interesting anti-inflammatory and anti-allergic properties when assessed in rats and mice. PMID- 11787943 TI - Pharmacological properties of A-204176, a novel and selective alpha1A adrenergic agonist, in in vitro and in vivo models of urethral function. AB - A-204176 (N-[5-(1H-imidazol-4-y1)-5,6,7,8-tetrahydro-1 naphthalenyl]methanesulfonamide) is a potent and selective alpha1A adrenoceptor agonist that binds with 17-fold and 9-fold greater affinity to the alpha1A (Ki=176 nM) than the alpha1b and alpha1d subtypes, respectively. In functional studies A-204176 is potent (pD2=6.4) and efficacious (83% of maximum control phenylephrine response) at rabbit urethra alpha1A receptors, with weaker potency and greatly reduced efficacy at rat spleen alpha1B (pD2=5.3, 11%) and rat aorta alpha1D (pD2=4.4, 10%) subtypes. In anesthetized female dogs, A-204176 is more potent than the non-selective alpha1 adrenoceptor agonist phenylpropanolamine (PPA) to increase measures of urethral tone and is more efficacious to increase pressure in the proximal region of the urethra. Significant increases on parameters of the urethral pressure profilometry were induced at 100 and 300 nmol/kg, i.v., by A-204176 and PPA, respectively. A-204176 was more potent than PPA to increase the abdominal pressure required to produce leakage. In the simultaneous measurement of intraurethral pressure and mean arterial blood pressure, A-204176 displays enhanced urethral selectivity relative to PPA. However, despite its selectivity for alpha1A versus alpha1B and alpha1D adrenoceptors in vitro, A-204176 did not display the degree of urethral selectivity in vivo that would have been expected. The observed effect of A 204176 on blood pressure may be due to the presence of extra-synaptic alpha1A adrenoceptors in the vasculature or to activation of spinal and supraspinal alpha1A adrenoceptors. These data indicate that A-204176 may represent a useful pharmacological tool to investigate the functional role of the alpha1A adrenoceptor in the urethra and to elucidate the lack of uroselectivity observed in vivo. PMID- 11787944 TI - Lysophosphatidic acid enhances airway response to acetylcholine in guinea pigs. AB - Inhalation of lysophosphatidic acid (LPA, 1-100 microg/ml) for 2 min enhanced the airway response induced by intravenous injection of ACh in guinea pigs. At 30 min after inhalation of LPA, the airway response to ACh was two fold higher than that before inhalation. This enhancement of airway response to ACh was partially inhibited by capsaicin desensitization or bilateral vagotomy. These results suggested that the enhancement of airway response to ACh induced by LPA may be due to the activation of capsaicin-sensitive fibers. It can be also contribute to bronchial asthma or other types of pulmonary disease such as cough variant asthma and atopic cough. PMID- 11787945 TI - Induction of cytochrome P450-dependent monooxygenase in mouse liver and kidney by rutaecarpine, an alkaloid of the herbal drug Evodia rutaecarpa. AB - Rutaecarpine is one of the main alkaloids of an herbal remedy, Evodia rutaecarpa, which has been used for the treatment of gastrointestinal disorder and headache. Effects of rutaecarpine on hepatic and renal cytochrome P450 (CYP)-dependent monooxygenase were studied in C57BL/6J mice. Treatment of mice with rutaecarpine by gastrogavage at 50 mg/kg/day for three days resulted in 57%, 41%, 6-, and 6 fold increases of hepatic microsomal benzo(a)pyrene hydroxylation, 7 ethoxycoumarin O-deethylation, 7-ethoxyresorufin O-deethylation, and 7 methoxyresorufin O-demethylation activities, respectively. However, the treatment had no effects on hepatic oxidation activities toward benzphetamine, N nitrosodimethylamine, nifedipine, and erythromycin. In the kidney, rutaecarpine treatment resulted in 2-fold and 42% increases of microsomal benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation activities, respectively. The treatment also increased renal 7-ethoxyresorufin O-deethylation activity to a detectable level. Immunoblot analysis of microsomal proteins showed that rutaecarpine-treatment increased the protein levels of CYP1A1 and CYP1A2 in the liver, whereas hepatic level of CYP3A-immunoreacted protein was not affected by rutaecarpine. These CYPs were not detectable in the immunoblot analyses of control and rutaecarpine-treated mouse kidney microsomes. These results indicated that rutaecarpine was a CYP1A inducer and showed potent inductive effects on both CYP1A1 and CYP1A2 in the liver. PMID- 11787946 TI - Fermented soybean-derived Touchi-extract with anti-diabetic effect via alpha glucosidase inhibitory action in a long-term administration study with KKAy mice. AB - A water-soluble Touchi-extract (TE) exerts a potent inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs, and elicited anti-glycemic effects in rats and humans with single-bolus oral administration. In the present study, genetically modified diabetic model KKAy mice were used to examine the long-term effects of TE. Eight-week-old male KKAy mice were fed with CE-2 chow containing 0.08 and 0.4% of TE for 60 days. In the latter group, fasting blood glucose levels decreased (6.68 +/- 0.41 mmol/L) significantly (p<0.05) after a 60 day ingestion period compared with controls (8.75 +/- 0.54 mmol/L). Moreover, postprandial blood glucose levels were also significantly reduced (16.79 +/- 2.28 mmol/L; p<0.01) after ingesting TE for only 30 days compared with controls (28.49 +/- 0.59 mmol/L). On oral TE treatment for 60 days, postprandial increases in the blood glucose level after oral loading of sucrose (2 g/kg) at 30 (p<0.05) and 60 (p<0.01) min were significantly depressed compared with controls. Indexes for serum lipids; viz., total cholesterol (p<0.05) and triglyceride (p<0.01) levels significantly decreased after TE ingestion. Indexes for hepatic functions, such as glutamic-oxaloacetic transaminase (p<0.01), glutamic-pyruvic transaminase and gama-glutamyl transpeptide levels, were similarly suppressed. Organ weights of the heart, kidney, jejunum, liver and spleen increased in control KKAy mice due to hyperinsulinemia. Interestingly, the respective organ weights decreased (p<0.05, 0.01) and the jejunum length was reduced (p<0.05) significantly in the TE-treated groups. All in all, TE demonstrated an anti-hyperglycemic effect and may have potential use in the management of non-insulin-dependent diabetic mellitus. PMID- 11787947 TI - Modulation of [3H]quinpirole binding at striatal D2 dopamine receptors by a monoamine oxidaseA-like site: evidence from radioligand binding studies and D2 receptor- and MAO(A)-deficient mice. AB - [3H]Quinpirole is a dopamine agonist with high affinity for the D2 and D3 dopamine receptors. A variety of monoamine oxidase inhibitors (MAOIs) inhibit equilibrium binding of [3H]quinpirole binding in rat striatal membranes suggesting that MAOIs interact with a novel binding site that is labeled by [3H]quinpirole or that allosterically modulates [3H]quinpirole binding. To determine whether the D2 receptor is essential for [3H]quinpirole binding and/or modulation of [3H]quinpirole binding by MAOIs, D2 receptor-deficient mice were studied. [3H]Quinpirole binding was decreased in D2 receptor-deficient mice to 3% of that observed in wild-type controls indicating that [3H]quinpirole binding is associated with the D2 dopamine receptors. Then, in an attempt to label the site mediating the modulation of [3H]quinpirole binding, binding of the MAOI [3H]Ro 41 1049 was characterized in rat striatal membranes. [3H]Ro-41-1049 labeled a single binding site with a pharmacological profile with respect to MAOIs that was similar to both [3H]quinpirole binding (Spearman r=0.976) and MAO(A) activity. To determine whether MAO(A) plays a role in the modulation of [3H]quinpirole binding by MAOIs, MAO(A)-deficient mice were examined. In these mice, [3H]Ro-41-1049 binding was decreased to 7% of wild-type control. [3H]Spiperone binding was unaltered. Spiperone-displaceable [3H]quinpirole binding was decreased to 43% of wild-type control; however, the remaining [3H]quinpirole binding in MAO(A) deficient animals was inhibited by Ro 41-1049 similar to wild-type. [3H]Ro-41 1049 binding was not decreased in D2 receptor-deficient mice. These data suggest that [3H]Ro-41-1049 labels multiple sites and that MAOIs modulate [3H]quinpirole binding to the D2 receptor via interactions at a novel, non-MAO binding site with MAO(A)-like pharmacology. PMID- 11787948 TI - Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats. AB - GYKI 52466 [1,4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine], a non-competitive AMPA/kainate receptor antagonist, administered i.p. at the dose of 5 mg/kg, exerted a significant anticonvulsant effect, as it decreased seizure and afterdischarge durations, being ineffective at 2 mg/kg. Subsequently, GYKI 52466 (2 mg/kg) was combined with antiepileptic drugs at doses ineffective in fully kindled rats. Co-administration of GYKI 52466 with clonazepam (0.003 mg/kg i.p.) resulted in a significant reduction of seizure severity (by 20%), seizure duration (by 31%) and afterdischarge duration (by 24%). Co-injection of GYKI 52466 with valproate (75 mg/kg i.p.) also resulted in the respective 8%, 16%, and 17% reductions of the three studied seizure parameters. No protection was observed when GYKI 52466 was co-administered with carbamazepine (20 mg/kg i.p.), phenobarbital (20 mg/kg i.p.), or diphenylhydantoin (40 mg/kg i.p.). Combinations of GYKI 524662 with antiepileptic drugs did not cause any significant motor (rotarod test) or long-term memory deficits (passive avoidance task). Only GYKI 52466 administered alone at 5 mg/kg, caused a significant impairment of retention in amygdala-kindled rats. The interaction at a pharmacokinetic level, at least in case of the combination of GYKI 52466 with valproate, can be excluded because GYKI 52466 did not interfere with the free plasma level of valproate. These results give further support to the idea of a potential clinical benefits of the combined treatment of AMPA/kainate receptor antagonists with some antiepileptic drugs. PMID- 11787949 TI - Neonatal treatment with 5,7-dihydroxytryptamine induces decrease in alcohol drinking in adult animals. AB - It has long been suggested that serotonin (5-HT) neurotransmitter system activity is associated with ethanol (ETOH) intake and dependence. The authors studied the effects of neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions on voluntary alcohol drinking in adult Wistar rats. At 3 days after birth animals were pretreated with desipramine (DMI) and then given a bilateral injection of 5,7-DHT into lateral ventricles. Afterwards, the rats were kept under standard laboratory conditions until at least 2 months of age following which they were tested. 5,7 DHT induced a marked and permanent decrease in brain 5-HT content, measured in the prefrontal cortex, hippocampus and striatum, but did not modify noradrenaline content in these structures. Lesioned animals, both males and females displayed lower preference for ETOH than sham-lesioned animals. Total fluid intake was significantly higher in 5,7-DHT-lesioned than sham-lesioned rats. A significant decrease in body weight was observed in 5,7-DHT-treated rats. This effect was not caused by a significant change in food intake. Both groups showed high preference for a 0.1% saccharin. In conclusion, the present results demonstrated that neonatal treatment with 5,7-DHT evoked long-lasting neurochemical changes and reduction of ETOH intake in adult rats. Neonatally 5,7-DHT-treated rats may be considered as a suitable model in further research on the relationship between the function of central 5-HT system and alcohol intake and dependence. PMID- 11787950 TI - Influence of clonazepam and carbamazepine on alcohol withdrawal syndrome, preference and development of tolerance to ethanol in rats. AB - The effects of clonazepam (0.3 and 1.0 mg/kg or 0.1 mg/kg, b.i.d., 5 days) and carbamazepine (50 and 100 mg/kg or 12.5 and 50 mg/kg b.i.d., 5 days) on alcohol withdrawal syndrome in rats were investigated. Moreover, the influence of clonazepam (0.3 mg/kg, single dose, or repeated doses for 8 days) and carbamazepine (50 mg/kg, single dose, or repeated doses for 8 days) on the development of tolerance to ethanol was also examined. To study the influence of clonazepam and carbamazepine on preference to ethanol, both drugs were administered for 5 days during the last week of the experiment, (clonazepam at 0.1 mg/kg, b.i.d., i.p. and carbamazepine at 12.5 mg/kg, b.i.d, i.p.). Clonazepam and carbamazepine administered at single doses as well as multiple doses diminished the symptoms of withdrawal syndrome. Clonazepam did not prevent the development of tolerance to sleep-inducing and hypothermal action of ethanol, while carbamazepine prevented the development of tolerance to hypnotic effect of ethanol. Carbamazepine clearly reduced preference to ethanol (significantly vs. the control group and vs. the baseline values). Clonazepam also diminished preference to alcohol, but only in comparison with baseline values. PMID- 11787951 TI - Increase in NAD but not ATP and GTP concentrations in rat liver by dehydroepiandrosterone feeding. AB - Dehydroepiandrosterone (5-androsten-3beta-ol-17-one; DHEA), the main circulating steroid in humans, has been described to exert varied beneficial effects including antiobesity, anti-aging and anticancer action when used at pharmacological doses in experimental animals. To elucidate the mechanism of the pleiotropic effects of DHEA, we studied the effect of this steroid on concentrations of NAD and adenine and guanine nucleotides in rat liver. Administration of DHEA at 0.3% in the diet for 7 consecutive days caused an increase in liver NAD and NADP, but was without effect on NADH concentrations. This indicates a shift of the redox couple (NAD/NADH) towards oxidation in the DHEA-treated rats. Moreover, there was no change in adenine and guanine nucleotide concentrations, which disproves the hypothesis that the DHEA anticancer actions are due to a decrease in the availability of nucleosides for DNA synthesis. The findings indicate that an increase in liver NAD pool and/or altered redox status, but no changes in adenine or guanine nucleotide content, may be involved in the pleiotropic effects of DHEA. PMID- 11787952 TI - Antianaphylactic and antiasthmatic properties of new piperazinyl 7-(beta hydroxypropyl)-theophylline derivatives in guinea pigs. AB - The present studies have demonstrated that new piperazinyl 7-(beta-hydroxypropyl) theophylline derivatives (R3, R6, R7) possess antihistamine, antianaphylactic and antiasthmatic properties. The compound R6 exerted especially pronounced selective protective action in experimental histamine asthma and provided effective prevention against anaphylactic shock in guinea pigs. The evidence was also presented that compound R6 inhibited in vitro mast cell degranulation induced by the preparation 48/80 liberating endogenous histamine. It was shown that the compound R6, i.e. 7-beta-hydroxy-gamma-[N1-(N4-benzyl)-piperazinyl)-theophylline efficiently competed with histamine of both endo- and exogenous origin and inhibited the mediator release from the mast cells. PMID- 11787953 TI - Effect of intraportal verapamil infusion on hepatic ischemia-reperfusion injury. AB - Removal of free oxygen radicals, generated during reperfusion of an ischemic organ by scavengers protects the tissue from reperfusion injury. The calcium channel blocker verapamil is an effective cytoprotective agent, preventing against reperfusion injury. The effects of verapamil were investigated previously using hepatic, renal or cardiac ischemia-reperfusion injury models. We investigated the effects of intravenous and intraportal administration of verapamil in prevention from the injury caused by free oxygen radicals generated during hepatic ischemia-reperfusion in rats. Thirty six male Sprague-Dawley rats after laparotomy were subjected to hepatic ischemia for 30 and 45 min followed by 60 min of reperfusion. Two minutes before ischemia the rats were pretreated by intravenous or intraportal administration of verapamil. The levels of glutathione and thiobarbituric acid reacting substances (TBARs) referred to as malonyldialdehyde (MDA) and the serum levels of transaminases were measured in liver tissue 1 and 24 h after the onset of reperfusion. Statistical analysis of the data by Student's t-test showed statistically significant differences between the group pretreated intraportally with verapamil and the other groups. Verapamil given intraportally exerted more beneficial effect. Therefore, we conclude that intraportal verapamil administration reduces the ischemia-reperfusion injury caused by free oxygen radicals. PMID- 11787954 TI - DNA-binding properties and cytotoxicity of extended aromatic bisamidines in breast cancer MCF-7 cells. AB - The DNA binding properties of three novel extended aromatic bisamidines (1-3) possessing different dicationic terminal side chains were studied. Data from the ethidium displacement assay showed that bisamidines 1-3 have significant affinity for DNA. We studied the cytotoxic activity of bisamidines 1-3 and Hoechst 33258 in the cultured breast cancer MCF-7 cells. These data show that in broad terms the cytotoxic potency of bisamidines 1-3 in the cultured breast cancer MCF-7 cells decreases with the size of the alkyl group substituent (cyclopropyl > isopropyl > cyclopentyl), in accord with their increases in DNA affinity, as shown by the binding constant values. The bisamidines 1-3 showed comparable antitumor activity to Hoechst 33258. PMID- 11787955 TI - Opposite effects of mast cell degranulation by compound 48/80 on peritoneal inflammation in Swiss and CBA mice. AB - The murine strains differ in the number of peritoneal mast cells. Degranulation of peritoneal mast cells by single injection of compound 48/80 (1.2 mg/kg) followed by zymosan-induced (2 mg/ml, 0.5 ml/mouse) peritoneal inflammation caused either inhibition or enhancement of an early influx (at 4 h of peritonitis) of exudatory leukocytes in Swiss and CBA mice, respectively. These opposite effects correspond with statistically significant differences in the number of peritoneal mast cells in the intact Swiss (11 x 10(3)) and CBA (39 x 10(3)) mice. PMID- 11787956 TI - Insidious dopamine: provocateur or protective agent in Parkinson's disease? PMID- 11787957 TI - Colostrinin and colostrinin-derived nonapeptide (colostral-val nonapeptide, CVNP) facilitate learning and memory in rats. PMID- 11787959 TI - The normal antireflux mechanism. AB - The normal antireflux mechanism consists of several components, any one of which may malfunction and render an individual prone to the development of GERD. The LES is clearly the most important component because gastroesophageal reflux almost always occurs when the sphincter pressure equals that of the stomach. Usually, an LES pressure of just 2 to 3 mm Hg above intragastric pressure is sufficient to prevent reflux. Other factors certainly play significant ancillary roles in preventing reflux. In the absence of a hiatal hernia, the crural fibers of the diaphragm serve as an "extrinsic" sphincter. Furthermore, the unique anatomy of the proximal stomach (e.g., the angle of His, mucosal flap valve, posterolateral location of the fundus) serves to keep gastric contents away from the gastroesophageal junction, making it less likely for reflux to occur when the LES relaxes. When a hiatal hernia is present, these factors are lost, and the hernia sac provides a reservoir for gastric juices with ready access to the LES. Finally, some degree of reflux occurs in all individuals, but esophageal clearance and acid neutralization provide an important last line of defense. PMID- 11787960 TI - Gastroesophageal reflux disease pathophysiology. AB - Gastroesophageal reflux disease is common in the Western world and affects a heterogeneous population. Structural and physiologic factors contribute to its pathophysiology, but the relative contribution of these individual factors varies between patients. Three main factors are generally central to the condition: TLESR, hypotensive LES tone, and hiatal hernia. In addition, several other factors (e.g., esophageal and gastric motility, salivary secretion, and mucosal defense mechanisms) modulate the extent of the injury produced by acid reflux. PMID- 11787961 TI - Evidence-based investigation for reflux disease. AB - Hiatal hernia and gastroesophageal reflux disease are measurable conditions. Evidence-based evaluation techniques should be applied to quantify these conditions, to standardize investigations, to define indications, and to provide objective results. PMID- 11787962 TI - The staging of severity in gastroesophageal reflux disease. AB - The concept of staging gastroesophageal reflux disease (GERD) has evolved in past decades. In 1974, it was recommended that a standardized method be used to assess the severity and degree of reflux; in 1988, it was proposed that staging be used to evaluate and to report GERD objectively. Some clinicians have since experimented with the staging system by reporting on definite forms of GERD, and others have offered ideas to improve the objectivity of evaluating and reporting GERD. PMID- 11787963 TI - Medical management of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) is the most frequent problem seen in the esophageal clinic and laboratory Most patients who have a small hiatal hernia or an occasional reflux require only symptomatic treatment and some lifestyle modifications. However, prolonged medical treatment becomes mandatory in more severe cases, and these patients must significantly modify their lifestyle and try to correct the underlying causes of their condition. PMID- 11787964 TI - Extraesophageal manifestations of reflux disease: myths and reality. AB - Because of the anatomic proximity of the esophagus and the upper respiratory tract, it is not surprising that, in some patients with GERD, symptoms attributable to the respiratory and upper aerodigestive tract may occur. The prevalence of respiratory or other extraesophageal manifestations of GERD remains unknown, however, primarily because in any given patient it is often difficult to determine whether GERD is causing the extraesophageal condition or whether the two conditions are coexisting independently. Acid can reflux into the hypopharynx or trachea in some patients with GERD, thereby causing a variety of respiratory tract symptoms. Additionally, vagovagal reflexes triggered by acid that comes in contact with the esophageal or tracheal mucosa may contribute to the pathogenesis of GERD-related respiratory symptoms, particularly wheezing and coughing. The clinician should be particularly suspicious of underlying GERD in patients with unexplained dental caries, posterior laryngitis, chronic unexplained cough, and intrinsic asthma that does not respond to (or worsens with) bronchodilator therapy. Intensive medical antireflux therapy should be instituted in patients with a suspected extraesophageal manifestation of GERD. Failure to respond to this should not lead automatically to antireflux surgery; the clinician should use 24-hour pH monitoring to document the relationship between GERD and extraesophageal complications and to demonstrate that intensive medical therapy has indeed failed to eliminate acid reflux. PMID- 11787965 TI - Reflux disease without mucosal damage: is there a place for surgery? AB - Patients in whom regurgitation is a major problem usually require antireflux surgery even though they may have no evidence of esophageal mucosal damage. The most common symptom of reflux is heartburn, and there is good evidence that the severity of this symptom does not correlate with the degree of mucosal damage in the esophagus. With the advent of laparoscopic surgery and the great reduction in the morbidity of antireflux surgery, many patients now are looking for cure of their reflux rather than just symptom relief. Patients in this category do well with laparoscopic antireflux surgery regardless of whether thee have endoscopic evidence of mucosal damage or not; indeed, if the data in the literature are a guide, it seems that esophageal mucosal damage is not a necessary indication for antireflux surgery. An "acid-sensitive esophagus" is not yet an established indication for laparoscopic antireflux surgery, however. PMID- 11787966 TI - Laparoscopic repair for simple ulcerative esophagitis: current results. AB - Laparoscopic fundoplication for minimal esophageal damage is feasible and reasonable in selected patients. This approach seems to be as safe as an open procedure; however, a period of learning is required to achieve maximum benefit. As experience is gained, the operative time, hospitalization time, conversion rate, and functional results improve. If one examines the change in quality of life before and after laparoscopic fundoplication, the full extent and significance of patient-related benefits still remain undefined. Length of follow up has yet to reach the level of that reported for open procedures. Continued evaluation and follow-up are necessary to assess the long-term effectiveness of laparoscopic Nissen fundoplication. PMID- 11787967 TI - Open antireflux repairs for simple reflux esophagitis: short- and long-term results. AB - This analysis of the results of open antireflux surgery clearly shows a benefit for antireflux surgery in most patients who have severe esophagitis with or without hiatal hernia. The authors of this article have found many variations in the methodology used to evaluate these results. Aside from these problems, however, the authors also have noticed the remarkably serious and honest work performed by most surgeons in trying to report the truth with the methodologies available to them. The principles of antireflux surgery can be found among the different studies that are reviewed in this article. These principles include: 1. The necessity of closing the crura; 2. The importance of repositioning the distal esophagus into the abdominal cavity; 3. The necessity of increasing the LES pressure by using the musculature of the fundus; 4. The preference for using a short and floppy fundoplication to avoid side effects; and 5. The need for long term follow-up in evaluating results. PMID- 11787968 TI - Reoperative antireflux surgery. AB - Antireflux surgery is a successful procedure in the treatment of severe gastroesophageal reflux disease. During this procedure, if the following four elements are observed, (1) adequate mobilization of the distal esophagus into the abdomen without tension, (2) construction of an appropriate fundoplication, (3) closure of the diaphragmatic crura, and (4) anchoring of the esophagogastric junction and fundoplication in the abdomen, the patient can be expected to achieve an excellent outcome from either a primary or a secondary antireflux operation. PMID- 11787969 TI - Paraesophageal hernias: open, laparoscopic, or thoracic repair? AB - The only treatment currently available for paraesophageal hernia is surgery, which is effective in most cases if the principles of operative therapy are followed. These principles include reducing the stomach, resecting the hernia sac, effectively closing the hiatus, and achieving sufficient gastropexy. The authors believe that a laparoscopic approach to paraesophageal hernias is safe and effective, allowing excellent visualization of the hiatus and superior esophageal mobilization, with significantly less physiologic insult to the debilitated patients in this population. Two questions remain, hoever. First, is an antireflux procedure necessary? The authors believe it is, because of the high rate of postoperative reflux. Additionally, the procedure does not add significant time to the overall operation and provides an excellent anchoring mechanism. Second, is there a higher rate of recurrence with laparoscopic repair? This concern, introduced by Hashemi et al, has not been raised by other authors. The authors have had few recurrences but currently are studying all of their asymptomatic patients for confirmation. For now, the authors consider laparoscopic paraesophageal hernia repair with Nissen fundoplication the procedure of choice for this difficult problem. PMID- 11787970 TI - Biliopancreatic reflux esophagitis: the role of the Roux-en-Y long-limb diversion. AB - Since the end of the nineteenth century, numerous operations were designed to relieve reflux of duodenal content into the stomach and hence the esophagus under certain conditions. The basic surgical principle remains almost invariably the confection of a long Roux-en-Y jejunal limb. The most effective remedial operations are the total duodenal diversion and the supra papillary duodenal diversion. Although the latter technique seems to avoid some of the worst postoperative side effects caused by antrectomy and vagotomy, its feasibility implies the absence of a previous gastrojejunostomy. PMID- 11787971 TI - Reflux esophagitis and scleroderma. AB - Despite improvement in pharmacologic management, the reflux seen in patients who have scleroderma is significantly greater than the reflux seen in patients who have idiopathic reflux. Furthermore, even with significant symptom improvement, half of the patients who have scleroderma do not show complete healing of esophagitis, owing to residual gastroesophageal reflux. Acid and bile reflux monitoring and endoscopic control examination should be used routinely to provide quantitative information on reflux damage and control. These patients need repeated adjustment of maintenance drug doses. PMID- 11787972 TI - Esophagectomy for gastroesophageal reflux disease. AB - Failed control of pathologic gastroesophageal reflux leads to irreversible esophageal damage and progressive loss of function. Patients develop severe intractable symptoms, incapacitating dysphagia, and, with end-stage disease, stricture formation or Barrett's esophagus. When medical management and repeated antireflux operations have failed, resection of the diseased esophagus may become the only valid alternative. Careful preoperative evaluation and patient selection are essential to obtain satisfactory long-term functional results with acceptable rates of morbidity and mortality. PMID- 11787973 TI - Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part II: amino acids for parenteral nutrition. AB - The presence of aluminium in amino acids parenteral nutrition solutions can be related to the affinity of the amino acids for aluminium present in glass containers used for storage. For this study solutions of 19 amino acids used in parenteral nutrition were stored individually in glass flasks and the aluminium measured at determined time intervals. Solutions of complexing agents for aluminium, as ethylene-diaminetetraacetic acid, nitrilotriacetic acid, citrate, oxalate and fluoride ions were also stored in the same flasks and the aluminium measured during the same time interval. The measurements were made by electrothermal atomic absorption spectrometry. The aluminium content of the glass containers was also measured. The results showed that the glasses have from 0.6% to 0.8% Al. Only solutions of cysteine, cystine, aspartic acid and glutamic acid became contaminated by aluminium. As the same occurred with the complexing agents, aluminum can be released from glass due to an affinity of the substances for aluminium. Comparing the action of complexing agents and amino acids for which the stability constants of aluminium complex are known, it is possible to relate the magnitude of the stability constant with the aluminium leached from glass, the higher the stability constant, the higher the aluminium released. The analysis of commercial formulations with and without cysteine, cystine, glutamic acid or aspartic acid stored in glass containers confirms that the presence of these amino acids combined with the age of the soLution are, at least partially, responsible for the aluminium contamination. The resuLts demonstrated that the contamination is an ongoing process due to the presence of aluminium in glass combined with the affinity of some amino acids for this element. PMID- 11787974 TI - The influence of dietary microbial phytase and calcium on the accumulation of cadmium in different organs of pigs. AB - A total of 72 barrows (initial body weight 16.7 kg) was used, to evaluate the influence of microbial phytase supplementation alone or in combination with calcium to barley soybean meal diets on the accumulation of cadmium (Cd) in kidney, liver, muscle, brain and bone. The control group received the basal diet with 6 g Ca and a low native Cd concentration of 0.03 mg/kg dry matter (DM). In the experimental groups 2, 3, 4 and 5 dietary cadmium concentration was elevated to 0.78 mg/kg DM. The diet of group 3 was supplemented with 800 U microbial phytase/kg, the diet of group 4 with 6 g Ca/kg. The diet of group 5 contained both supplements. The addition of microbial phytase caused an increase of Cd retention in kidney and liver at 30 and 50 kg body weight. This effect was counteracted by the contemporary addition of calcium. A supplementation of Ca alone showed no effect on the Cd accumulation in kidney and liver. In muscle, brain and bone no effects of phytase and calcium on the accumuLation of Cd could be found. PMID- 11787975 TI - Trace element levels in the experimental peritonitis. AB - Electron transfer from iron or copper ions to oxygen is an important example of cellular free radical initiation. Oxygen derived free radicals have been implicated as mediators of cellular injury in several model systems. To evaluate the importance of iron, copper and zinc levels on lipid peroxidation in peritonitis, we measured peritoneum malondialdehyde (MDA) as a marker of lipid peroxidation, zinc, copper, and iron levels during an animal model of intraperitoneal sepsis. Additionally the effects of the free radical scavenger alpha-tocopherol administration was studied. The peritoneum MDA, iron, copper and zinc levels were increased after induction of peritonitis with Escherichia Coli. The treatment with alpha-tocopherol was decreased the peritoneum MDA, iron and copper levels significantly, except the zinc level (p < 0.001, p < 0.001, p < 0.001, respectively). Additionally the alpha-tocopherol treatment for three days prior to injection of E.Coli more decreased MDA, copper and iron levels than that of the treatment with alpha-tocopherol at the time of injection of E. Coli (p < 0.001, p < 0.001, p<0.001, respectively). Our results indicated that copper, iron and zinc had important effects on peroxidation events in E. Coli induced peritonitis, and alpha-tocopherol treatment can improve the oxidant status. PMID- 11787976 TI - Plasma and erythrocytes antioxidant status and trace element levels in proteinuric patients with moderate glomerular function. AB - The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes. PMID- 11787977 TI - Blood pressure in relation to dietary calcium intake, alcohol consumption, blood lead, and blood cadmium in female nonsmokers. AB - The interrelationship of dietary calcium (Ca) intake, alcohol consumption, blood lead (BPb), blood cadmium (BCd), age, and body mass index (BMI) to blood pressure was examined in 267 peasant women 40-85 years of age. They were residents of two rural areas in Croatia and differed with regard to dietary Ca intake: 100 women with low Ca intake (approximately 450 mg/day) and 167 women with relatively high Ca intake (approximately 940 mg/day). All of the women were nonsmokers and consumed very little or no alcohol. Median and range BPb values were 74 (29-251) microg/L in women with low Ca intake and 59 (21-263) microg/L in women with high Ca intake (p < 0.0002), whereas corresponding BCd values were 0.6 (0.2-3.6) microg/L and 0.6 (0.3-4.5) microg/L (p > 0.10). Results of multiple regression showed a significant (p < 0.05) increase in systolic blood pressure with age, BMI, and BCd, and marginally with alcohol consumption (multiple r = 0.48, p < 10( 6)). An increase in diastolic blood pressure was significantly (p < 0.05) associated with BMI, age, and residence area (i.e., it was higher in women with low Ca intake), and marginally with BCd, and alcohol consumption (multiple r = 0.38, p < 10(-6)) When the two groups of women with different Ca intake were subdivided into consumers and nonconsumers of alcohol, BPb was related positively to alcohol consumption and inversely to Ca intake. The highest BPb was found in the subgroup of alcohol consumers with low Ca intake, and the lowest BPb in the subgroup of nonconsumers with high Ca intake: 78 (42-251) microg/L and 51 (22 192) microg/L, respectively (p < 10(-8)). Diastolic blood pressure was significantly higher in the former subgroup as compared to the latter: 95 (72 130) mm Hg and 90 (60-120) mm Hg, respectively (p < 0.05). This cannot be explained by age, BMI, or BCd, which were comparable in the two subgroups. The results indicate that alcohol consumption and low Ca intake can increase BPb, which may significantly contribute to an increase in diastolic blood pressure in female nonsmokers even at relatively low-level Pb exposure. PMID- 11787978 TI - Mineral supplementation of white wheat flour is necessary to maintain adequate mineral status and bone characteristics in rats. AB - This experiment was designed to compare the effect of ingestion of a wheat flours on mineral status and bone characteristics in rats. White flour was tested either without further mineral supplementation or with Mg, Fe, Zn and Cu supplementation. The flour diets were compared to a control purified diet. Four groups of 10 male Wistar rats each were fed one of the experimental diets for 6 wk and mineral status and tissue retention as well as bone characteristics were determined. As expected, mineral intake, except for calcium, was significantly lesser in rats fed the white flour diet than in the other groups. The rats fed the white flour diet had the lowest food intake, weight gain, fecal excretion and intestinal fermentation. The most important result was that Mg and Fe status were drastically lower in rats fed the white flour diet than in those fed whole flour or control diets. The status of these both elements were significantly improved by the mineral supplementation of white flour. There were no major significant differences between mineral-supplemented white flour and whole flour groups in mineral status. Furthermore, bone mineral densities (total, metaphyseal and diphyseal) were significantly lower in rats fed white flour diet compared to the other diet groups, while no significant difference was observed between the mineral-supplemented white flour, whole flour or control diet groups. In conclusion, the present work shows clearly the importance of mineral supplementation of white wheat flour to sustain an adequate intake of minerals. Our results indicate also that the whole wheat flour did not negatively alter mineral bioavailability, in comparison to mineral supplemented white flour. Clinical studies are still needed to confirm these rat results in human. PMID- 11787979 TI - Inhibitory effect of aluminum on dopamine beta-hydroxylase from bovine adrenal gland. AB - Aluminum is a well known neurotoxic agent that is overaccumulated in the substantia nigra of patients affected by Parkinson's disease as well as in certain cerebral areas of other neurodegenerative pathologies such as Alzheimer's disease. Although the role of aluminum in neurodegenerative diseases is yet to be clearly understood, the metal ion is known to substantially alter the activity of several key enzymes in the central nervous system. The present paper reports data on the effect of aluminum on the activity of dopamine-beta-hydroxylase from bovine adrenaL gland utiLized as a model study. The metal ion inhibited the activity of this enzyme with a mixed type mechanism following the Michaelis Menten equation. In the absence of Al, the enzyme exhibited a Km and Vmax of 2.56 mM of 4.12 pmol/min respectively, while in the presence of Al its Km and Vmax were 3.85 mM and 2.86 pmol/min respectively. The potential implications of aluminum in the etiopathogenesis of neurological disorders are discussed. PMID- 11787981 TI - Molybdenum in infancy: methodical investigation of urinary excretion. AB - PROJECT: The clinical evaluation of trace element metabolism in infancy is based on optimal pre-analytical procedures. Urinary molybdenum excretion, the major determinant of its retention, was investigated to deduce criteria for representative specimen collection. PROCEDURES: 1.) Molybdenum concentration was analyzed in 24-hour urinary specimens (n = 193) to evaluate the range in pediatric patients. 2.) In 20 children aged 0.4 to 9.3 (mean 2.3) years admitted for a micturition cystourethrogram, three urinary collection methods (catheter, spontaneous midstream samples, urinary collection bags) were compared. 3.) Diurnal variations of molybdenum concentration were assessed by fractional urinary colLection in preterm infants fed infant formula or human milk (n = 10). Analysis was performed using atomic absorption spectroscopy. RESULTS: 1.) The molybdenum concentration in 24hour specimens was 4.0 (0-123) microg Mo/l. 2.) Urine gained by catheter collection (n = 20) rendered 7.0 (0.5-60.1) microg Mo/l, midstream samples and the use of urinary collection bags showed a concentration of 21.25 (0-91) microg Mo/l (p > 0.05). 3.) Fractional collection over 72 hours rendered a significant increase in only one participant. Diurnal differences of the urinary molybdenum concentration were significant between 3-6 p.m. and 6-9 p.m.. The molybdenum/creatinine quotient differed between the time intervals 3-6 p.m. and 9-12 p.m., as well as 9-12 a.m. and 6-9 a.m. (p < 0.05). CONCLUSION: Pediatric routine procedures are suitable for the assessment of urinary molybdenum excretion. The diurnal variations assessed are of minor clinical relevance, but should be considered by respective definition of collecting times and reference values. PMID- 11787980 TI - The impact of metal-ions on the activity spectrum of aqueous peat extract on the smooth musculature. AB - PROJECT: The results of our recent studies prove the stimulating effect of aqueous peat extract (APE) on the spontaneous contractile activity (SCA) of the smooth musculature. Only substances with a molecular weight of <3,000 Dalton are able to evoke any effect. As we know from the corresponding literature, trace elements as for instance copper, manganese, lead and cadmium do also influence the SCA even when they appear in low concentrations (micromol-range). The purpose of this study therefore is to examine the influence of the trace-elements on the inspected stimulating effects which aqueous peat extract has on the SCA. PROCEDURE: During in-vitro experiments with smooth muscles in organbaths, it has been examined--under application of a standardized method--if trace-elements are the cause for the stimulating effect of aqueous peat extract on the SCA of the smooth musculature. RESULTS: The results have shown that--independent from their concentration within the peat - the trace-elements do not influence the SCA of the smooth muscles. CONCLUSION: The results can be explained by the chelating capacity of the peat-components, that leads to the absorption of the trace elements. Additionally we can conclude that organic substances are the exclusive reason for the described effects. PMID- 11787982 TI - Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease. AB - PROJECT: Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. PROCEDURE: a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. RESULTS: the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. CONCLUSIONS: 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas. PMID- 11787983 TI - Selenium, glutathione peroxidases, and some other antioxidant parameters in blood of patients with chronic renal failure. AB - In the present study several parameters associated with oxidative stress were examined in the blood of 25 chronic renal failure (CRF) patients and the results were compared with 18 healthy subjects. Mean creatinine concentration in patients was 1,216 +/- 292 micromol/l. Selenium (Se) concentration in red cells, whole blood and in plasma of CRF patients (106 +/- 32.5, 59.0 +/- 16.7 and 42.4 +/- 13.8 ng/ml, respectively) was significantly (0.0001 < P 0.01) lower (by 20-42%) compared with the controls. Red cell and plasma glutathione peroxidase (GSH-Px) activities (16.6 +/- 3.4 U/g Hb and 93.7 +/- 32.9 U/l plasma) were lower by 12 and 53% (P < 0.05 and < 0.0001, respectively) in patients than in healthy subjects. GSH concentration in red cells of patients (2.81 +/- 0.45 mmol/l) was significantly (P < 0.001) higher (by 20%) than in control group. Malonyldialdehyde (MDA) concentration (expressed as thiobarbituric acid-reactive substances) in red cells of patients (725 +/- 155 nmol/g Hb) was significantly (P < 0.001) higher (by 28%) than in control group. No significant difference was observed in the activity of superoxide dismutase in pLasma between the two groups. In conclusion, our results confirm that the aLterations in Se levels in blood components and in GSH-Px activity in plasma show that the kidney plays an important role in Se homeostasis and in plasma GSH-Px synthesis. PMID- 11787984 TI - Prophylactic iron supplementation in pregnant women in Norway. AB - In the present study 67 non-anaemic women were randomly allocated to either 100 mg or 15 mg iron daily at about the 10. week of pregnancy. At about week 18, 30 and 36 of pregnancy, as well as 6 weeks after delivery, hemoglobin and the serum concentrations of ferritin, vitamin B12, folates, Zn, Cu and Se were monitored. Dietary allowances of other minerals and vitamins are also increased in pregnancy, and the 15 mg iron tablet was enriched with Zn (10 mg), Cu (2 mg), Se (50 microg), vitamin B12 (3 microg), and folate (0.1 mg). Neither ferritin, nor Cu, Zn or Se concentrations differed statistically significantly between the treatment groups during pregnancy. Ferritin and Zn appeared to decrease approximately parallel to the hemodilution, whereas Cu concentrations increased from a non-pregnant reference mean of 18 micromol Cu/L to a maximum mean of nearly 33 micromol Cu/L during pregnancy. Se decreased concomitantly to about 1.0 micromol Se/L. Serum folate (around 15 micromol/L) was essentially unaffected by pregnancy in the group given multivitamin/mineral supplementation, whereas the mean concentration fell below 10 micromol/L in the group supplemented with 100 mg iron daily. Our results indicate that supplementation of 15 mg Fe daily during pregnancy results in a small reduction of hemoglobin. It is suggested that additional supplementation with folate might be of importance to maintain the serum folate concentration during pregnancy. PMID- 11787985 TI - Zinc supplementation increases bone alkaline phosphatase in healthy men. AB - Zinc takes part in the metabolism of bone as a constituent of the matrix and as an activator of several metallo-enzymes. Animal in vitro and in vivo studies strongly suggest that zinc supplementation could stimulate bone formation and inhibit bone resorption but data in humans remain rare. The biological effects of 50 mg zinc given orally as gluconate in 20 healthy male volunteers were investigated in a 12 weeks double-blind placebo-controlled randomized trial. To investigate bone turnover, total alkaline phosphatases activity (ALP), bone specific alkaline phosphatase activity (BAPE) and BAP mass (BAP-M) concentration were measured as parameters of bone formation while urine calcium and C-terminal collagen peptide were determined as parameters of bone resorption. Samples were obtained in fasting subjects at baseline and after 6 and 12 weeks. In zinc treated subjects, a significant increase was observed at least after 12 weeks in total ALP (p < 0.01), BAP-M (p < 0.05) and BAP-E (p < 0.02). These parameters did not significantly change in the placebo group. Urine zinc/creatinine ratio significantly increased after 6 (p < 0.03) and 12 weeks (p < 0.04) in the zinc treated group and was significantly different from the placebo group (p < 0.002). There was no significant effect of zinc supplementation on parameters of bone resorption. In conclusion, zinc supplementation at supraphysiological doses increased parameters of bone formation in healthy men while parameters of bone resorption remained unchanged. PMID- 11787986 TI - Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain. AB - The cause of low back pain is heterogeneous, it has been hypothesised that a latent chronic acidosis might contribute to these symptoms. It was tested whether a supplementation with alkaline minerals would influence symptoms in patients with low back pain symptoms. In an open prospective study 82 patients with chronic low back pain received daily 30 g of a lactose based alkaline multimineral supplement (Basica) over a period of 4 weeks in addition to their usual medication. Pain symptoms were quantified with the "Arhus low back pain rating scale" (ARS). Mean ARS dropped highly significant by 49% from 41 to 21 points after 4 weeks supplemention. In 76 out of 82 patients a reduction in ARS was achieved by the supplementation. Total blood buffering capacity was significantly increased from 77.69 +/- 6.79 to 80.16 +/- 5.24 mmol/L (mean +/- SEM, n = 82, p < 0.001) and also blood pH rose from 7.456 +/- 0.007 to 7.470 +/- 0.007 (mean +/- SEM, n = 75, p < 0.05). Only intracellular magnesium increased by 11% while other intracellular minerals were not significantly changed in sublingual tissue as measured with the EXA-test. Plasma concentrations of potassium, calcium, iron, copper, and zinc were within the normal range and not significantly influenced by the supplementation. Plasma magnesium was slightly reduced after the supplemenation (-3%, p < 0.05). The results show that a disturbed acid-base balance may contribute to the symptoms of low back pain. The simple and safe addition of an alkaline multimineral preparate was able to reduce the pain symptoms in these patients with chronic low back pain. PMID- 11787987 TI - Molybdenum metabolism: stable isotope studies in infancy. AB - The essential trace element molybdenum (Mo) is bound to and required for the function of molybdoenzymes, e.g. sulfite and xanthine oxidase. Dietary recommendations for early infancy are based on limited knowledge about its metabolism. 100Mo was used as an extrinsic tag to study the absorption and kinetics of excretion in infancy. 10 infants with a gestational age of 35 (30-39) weeks, a birth weight of 2.0 (0.9-2.3) kg and a post-natal age of 20 (10-54) days were studied. They received 25 microg 100Mo/kg with a feed of human milk or formula. Fractional urinary and fecal collections were conducted preceding the 100Mo intake and for 48-72 hours afterwards. The materials were analyzed by atomic absorption spectroscopy and inductively coupled plasma mass spectrometry. The median absorption of 100Mo intake was 97.5 (96.3 to 99.1) %. The retention of nutritive Mo intake and 100Mo in the study period was 11.2 (3.8-15.7) microg Mo/kg, equivalent to 35.7 (12.7-55.6) %. The Mo concentration increased to a peak value in urine within 8 (6-13) hours and in feces within 24 (7-48.5) hours. In addition, increases of copper in feces and urine were observed in 8 of 9 infants studied. Mo given orally is well resorbed in premature infants, and predominantly excreted in the urine. Dietary recommendations should prevent excessive intakes in infancy. PMID- 11787989 TI - Review of publications. PMID- 11787988 TI - Oxidase activity of ceruloplasmin and concentrations of copper and zinc in serum of cancer patients. AB - A balance between oxidant carcinogens and endogenous antioxidant defence is of particular relevance to the carcinogenesis. Ceruloplasmin (Cp) carries up to 90% of Cu in plasma and performs ferroxidase, antioxidant and amine oxidase activity. Cu and Zn, as trace elements, have been recognized to play an important role as cofactors of SOD. The study presents the relationship of the Cp oxidase activity and concentrations of Cu and Zn in serum of 62 patients with breast (BCA), lung (LCA), gastrointestinal (GICA) and gynecological (GYNCA) cancer. The Cp oxidase activity was determined in serum with o-dianisidine as a substrate. Cu and Zn concentrations in serum were measured by using atomic absorption spectrometry. The results of the study have shown significant increase in the mean serum Cp oxidase activity and total Cu concentrations in all patient groups compared with the control one. The total mean serum Zn concentration was found to be decreased only in LCA group as compared with the control. The effect of the cancer progress on the Cp oxidase activity and concentrations of Cu and Zn was observed within the group of all cancer patients (ALLCA) and within the GICA group. The only significant difference in Cu concentrations among various stages of the disease was observed in GICA between local and distant one. Significant positive correlation coefficients were caLculated for the Cp activity and Cu concentrations in the control group and all patients groups, also according to the cancer progress. Future research is needed to evaLuate the consequences of the elevation of the serum Cp oxidase activity and concentration of Cp, Cu and Zn for the host antioxidant-oxidant balance. PMID- 11787990 TI - The relation between selenium, zinc and copper concentration and the trace element dependent antioxidative status. AB - An imbalance in the antioxidative system was connected with the development of a number of pathological processes. In order to receive values of a healthy group and to evaluate pathological changes of the trace element dependent antioxidative status in future, we investigated 99 healthy volunteers (45 male and 54 female, mean age 37.4 +/- 11.7 years). We determined the concentrations of Se, Cu and Zn, the concentrations of malondialdehyde (MDA) and the activities of the Se dependent glutathione peroxidase (GSH-Px) and the Zn/Cu dependent superoxide dismutase (SOD). The plasma concentrations (mean +/- SD) for Se, Cu and Zn were 0.84 +/- 0.10 micromol/l, 15.6 +/- 2.78 micromol/l and 12.6 +/- 1.80 micromol/l, resp., and for non protein-bound and protein bound MDA 0.27 +/- 0.07 micromol/l and 1.11 +/- 0.25 micromol/l, resp. The activity of GSH-Px in plasma and erythrocytes was 130 +/- 20.8 U/l and 19.8 +/- 4.18 U/mg Hb, resp. and of SOD in erythrocytes 3,159 +/- 847.2 U/g Hb. In plasma positive correlations have been found between Se concentrations and GSH-Px activities (p < 0.002, r = 0.31) and between GSH-Px activities and concentrations of non protein-bound MDA (p = 0.004, r = 0.28). A negative correlation has been observed between GSH-Px activities in plasma and in erythrocytes. The higher the concentrations of Cu in erythrocytes, the higher were the activities of SOD (p = 0.03, r = 0.22) and GSH-Px in erythrocytes (r = 0.26, p = 0.01), while an increasing activity of GSH-Px in these cells correlated with a decreasing concentration of non protein-bound MDA (r = -0,31, p = 0.002). An increase in BMI was connected with an increase in protein-bound MDA and a decrease in GSH-Px activities in pLasma (p = 0.002 and r = 0.23). As the results demonstrate, Se and Cu concentrations in erythrocytes can improve the trace element dependent antioxidative status. PMID- 11787991 TI - Trace metals in oral mucosa in relation to the lichen ruberplanus pathology. A preliminary study carried out by neutron activation analysis. AB - Lichen ruberplanus, contact allergy and hypersensitivity can be linked to oral exposure to metals released from metal alloys commonly used in dentistry. In this context neutron activation analysis was developed for the microdetermination of 36 elements in oral mucosa biopsies of two patients affected by lichen ruber planus and of five subjects as control group. In order to minimise metal contamination during sample collection, biopsies were taken by laser bistoury technique and then submitted to radiochemical neutron activation analysis (RNAA). Among the metals analysed, chromium showed obvious high concentration in gingival biopsies of the two pathological subjects compared to the corresponding tissues of control group. Cobalt and nickel were also determined in higher concentrations, but only in one of the oral mucosa of the two patients. The present findings way support the hypothesis concerning a potential link of lichen ruber planus condition with the exposure to Cr, Co and Ni as released into oral cavity from prosthodontic alloys. PMID- 11787992 TI - Serum zinc levels and zinc binding capacity in thalassemia. AB - Recently, it has been reported that serum zinc binding capacity (ZnBC) is a very important criterion to evaluate body zinc (Zn) status. It has been shown that chronic Zn deficiency occur in the patients with thalassemia major (TM). Zn deficiency in TM may cause hyperzincuria, high ferritin levels, hepatic iron load, hepatic dysfunction. This study was undertaken to determine serum Zn levels and ZnBC in different thalassemia forms and sickle cell disease (SCD). The study has been carried out on 30 Thalassemia Major (TM), 34 Thalassemia Intermedia (TI), 31 Thalassemia Trait (TT) and 10 SCD. As control group,13 healthy children and 20 adults were included. Serum Zn and ZnBC were determined by atomic absorption, then saturation index (SI%: serum Zn/ZnBC x 100) was calculated. Serum Zn levels in all patients were lower than control (p < 0.01). Serum ZnBC was at a normal level in patients with TT and TI but it was found to be lower in TM and SCD than control (p < 0.01). While serum Zn levels decrease and ZnBC increase in nutritionaL Zn deficiency, serum Zn levels decrease but ZnBC doesn't increase in patients with thalassemia. PMID- 11787993 TI - Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat. AB - The mechanisms responsible for the neurotoxic effects of Al remain poorly understood. In order to determine whether Al promotes oxidative stress in vivo, we measured the enzymatic activity of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) in four groups of rats after eight days of intraperitoneal administration of variable concentrations of Al (0, 5, 10, and 15 mg/kg body weight, respectively). XO activity was measured in both plasma and liver samples, and the activities of the remaining enzymes were further determined in the brain and red blood cells (RBC). The most significant changes were observed in XO and GPX activities, that were enhanced and depressed, respectively. In both instances, the enzyme activities were correlated with Al concentrations, either positively (XO) or negatively (GPX). Enhancement of XO and inhibition of GPX activity may lead to the accumulation of intermediate toxic compounds such as hydrogen peroxide and hydroxyl radicals, since SOD activity is increased as well. The latter finding must be taken with some caution because previous studies have shown contradictory results in this field. Our data suggest that Al toxicity could be mediated by its action on both pro- and anti-oxidant enzymes. The biological significance of these findings remains to be established. PMID- 11787994 TI - Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part I: salts, glucose, heparin and albumin. AB - The presence of aluminium (Al) in pharmaceutical products used parenterally as sodium and potassium chlorides, glucose, heparin and albumin were investigated with respect to their storage in glass containers. As glasses can have aluminium in their composition, the aluminium may be released from the glass into the solution. The action of the substances above mentioned were investigated storing their solutions in glass and plastic containers, and measuring the aluminium in solution at determined time intervals. The aluminium present in the commercial pharmaceutical products, stored in both plastic and glass containers were also measured. All glass containers were analysed to determine their aluminium content. The aluminium determinations were done by atomic absorption spectrometry. The resuLts showed that aluminium is present in all analysed glasses in a percentage of 0.6 to 3%. Although all substances already have a residual aluminium contamination, the major contribution comes from the glass containers in which their solutions were stored. The contamination arising from glass depends too much on the nature of the substance. While the salts extracted about 400 microg Al/l in 60 days, glucose extracted 150 microg Al/l, and albumin and heparin about 500 microg Al/l in the same time interval. Commercial solutions of glucose contain about 10 microg Al/l when stored in polyethylene and from 350 to 1,000 microg Al/l when in glass ampules. Considering all commercial products, solutions stored in plastic containers contained no more than 20 microg Al/l whereas in glass the aluminium contamination reached 1,000 microg/l, and in all of them the aluminium increases with the age of the product. PMID- 11787995 TI - Chromogenic urinary tract infection medium: evaluation and introduction for routine urine culture in a large clinical microbiology laboratory. AB - Evaluation and introduction of a chromogenic urinary tract infection (UTI) medium for the primary culture of routine urine specimens in a very large clinical microbiology laboratory is described. A modified scheme for the direct identification of the main groups of organisms causing UTI has led to quality improvements, with enhanced discrimination of mixed cultures and in efficiencies in staffing and working time that counterbalance increases in media costs. These improvements, together with the concurrent introduction of boric acid preservative for specimens from general practice, significantly reduced the level of positive results by 4.6% (2383 specimens) over an eight-month period (P <0.001). Chromogenic medium provided a reliable alternative to CLED medium for the routine culture of urine specimens. PMID- 11787996 TI - Effect of L929 cell-conditioned medium on antioxidant capacity in RAW264.7 cells. AB - Previously, we found that macrophage colony-stimulating factor (M-CSF) could reduce tert-butyl hydroperoxide (tbOOH)-induced oxidative injury in monocytes/macrophages. In order to find the mechanism by which M-CSF achieves this, we investigate the effect of M-CSF on the antioxidant system in murine macrophage RAW264.7 cells, using L929 cell-conditioned medium (L929-CM) as the source of M-CSF. The results show that L929-CM increased selenium-dependent glutathione peroxidase, non-selenium-dependent glutathione peroxidase, and catalase activities; and it increased reduced glutathione (GSH) but decreased lipoperoxide content in RAW264.7 cells. L929-CM-treated cells maintained their antioxidant capacity (including antioxidant enzyme activities and GSH content) when challenged with tbOOH. We conclude that M-CSF from L929-CM reduces oxidative injury in RAW264.7 cells by increasing antioxidant enzyme activity and improving redox status. PMID- 11787997 TI - Angiotensin II type-1 receptor antagonist, CS-866, reduces blood pressure without affecting glucose/insulin metabolism in cholesterol-fed rabbits. AB - CS-866 is an angiotensin II type-1 receptor antagonist, the effects of which on systolic blood pressure (BP) and glucose/insulin metabolism are investigated under hyperlipidaemic conditions produced by cholesterol feeding. Thirty-two female Japanese White rabbits (two months old) were assigned randomly into a CS 866-treated group (n = 17) fed a food admixture that contained 0.03% CS-866 and 0.2% cholesterol, or into a control group (n = 15) fed a food admixture containing 0.2% cholesterol only. Systolic BP was measured by an ear-cuff method. Glucose and insulin metabolism was characterised quantitatively from the results of an intravenous glucose tolerance test by a minimal model technique reported previously. After six months treatment, systolic BP in the CS-866-treated group was lower than in the control group (105 +/- 14 mmHg versus 115 +/- 18 mmHg; P <0.05), as assessed by analysis of variance and the Wilcoxon rank-sum test. No significant differences were seen in plasma aldosterone concentration, plasma renin activity, or angiotensin-converting enzyme activity between the groups. Administration of CS-866 for six months did not affect either glucose tolerance or insulin sensitivity. Other model parameters such as basal (steady-state) insulin and glucose concentration, first- and second-phase post-hepatic insulin delivery to glucose, and insulin clearance rate constant were unaffected. In conclusion, CS-866 treatment reduced systolic BP without affecting glucose/insulin metabolism under hyperlipidaemic conditions produced by cholesterol feeding. PMID- 11787998 TI - In vitro inhibition of head and neck cancer-cell growth by human recombinant interferon-alpha and 13-cis retinoic acid. AB - Three nasopharyngeal carcinoma (NPC) cell lines (CNE-1, CNE-2 and NPC/HK-1), two squamous cell carcinoma (SCC) cell lines (T2/CUHK and PWH-S1) and six head and neck cancer specimens (NPC [n = 4], SCC tongue [n = 1] and a thyroid cancer [n = 1]) were incubated with interferon (IFN)-alpha (5 x 10(4) iu/mL) and/or 13-cis retinoic acid (13RA; 10(-5) mol/L) for two days at 37 degrees C. In vitro chemosensitivity was measured using MTT assay. Mild growth inhibition of the five cell lines by IFN-alpha ranged from 7.1% to 51.8% (mean: 18.5%), whereas with 13RA it was zero to 19.7% (mean: 7%). Greater inhibition (14.8-51.0%, mean: 31.8%) was achieved when the two drugs were used in combination. Growth inhibition of the six surgical specimens ranged from 6.9% to 21% (mean: 13.6%) with IFN-alpha; zero to 10.3% (mean: 6.0%) with 13RA; and 6.6-26.5% (mean: 17.7%) when the two agents were combined. Four of the 11 samples showed synergistic antitumour effect when IFN-alpha and 13RA were combined, and six showed subadditive effect. The results show that IFN-alpha and 13RA have a mild in vitro antitumour effect on head and neck cancer cells, and the drug synergistic effect demonstrated in this study suggests that the two agents should be used in combination in clinical application. PMID- 11787999 TI - Automated non-culture-based sequence typing of meningococci from body fluids. AB - In recent years, the polymerase chain reaction has been used for the non-culture diagnosis of meningococcal disease, and sequence-based typing takes this further by providing the full characterisation normally only available by culture. In this study, porA gene sequencing was used to perform non-culture-based sequence typing of Neisseria meningitidis strains direct from body fluids. Non-culture porA gene sequencing provided the serosubtype of the infecting organism, and proved to be a useful method as N. meningitidis was not isolated from any of the patients in this study. In conclusion, porA gene sequencing is a very useful tool for the non-culture characterisation of meningococci and provides important information for public health management of cases and contacts. PMID- 11788000 TI - Detection of Chlamydia trachomatis in genitourinary medicine clinic attendees: comparison of strand displacement amplification and the ligase chain reaction. AB - Nucleic acid amplification (NAA) methods for the diagnosis of genital Chlamydia trachomatis infection perform well but are technically demanding. Strand displacement amplification (SDA) assay is a new NAA method that offers technical simplicity but its comparative diagnostic performance is unknown. Here, we compare the diagnostic performance of ligase chain reaction with that of SDA in first-catch urine (FCU) samples from both male and female patients and in endocervical swab (ECS) specimens. Attendees (715 men, 291 women) of a city centre genitourinary medicine clinic were studied. FCU specimens were collected from all the men and from 205 of the women in the study. Two ECS specimens were collected from each of the women. Discordant results were resolved using an in house nested polymerase chain reaction technique. Samples positive in two out of the three assays were considered positive. Prevalence of C. trachomatis infection was 9.2% and 9.1% in the men and women, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of SDA in FCU specimens from the men were 95.5%, 100%, 100% and 99.5%, respectively. In the female group, the figures for FCU and ECS specimens were 77.3%, 100%, 100% and 97.3%, and 90.9%, 100%, 100% and 97.3%, respectively. In this high-prevalence population, SDA assay is an effective method for the detection of C. trachomatis in FCU specimens in men and in ECS (but not FCU) specimens in women. Further studies in lower-prevalence populations are required. PMID- 11788001 TI - Helicobacter pylori detection in Chinese subjects: a comparison of two common DNA fingerprinting methods. AB - This study aims to demonstrate DNA diversity in Helicobacter pylori strains obtained from patients with peptic ulcer disease and compare the results from two DNA fingerprinting techniques. H. pylori strains (n = 42), collected from June 1996 to August 1999, were cultured from storage at -80 degrees C. DNA diversity was determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis, and random amplified polymorphic DNA (RAPD) PCR. Isolates showed a significant DNA sequence diversity by both methods. RAPD PCR demonstrated 33 distinct strain-specific band patterns, whereas PCR-RFLP demonstrated six distinct restriction patterns. PCR-RFLP identified four of the 42 strains as mixed growth, compared with RAPD-PCR which did not reveal any co colonisation. Diversity among H. pylori clinical isolates was demonstrated distinctly by both methods; however, RAPD-PCR showed greater discriminatory power in distinguishing between isolates. PMID- 11788002 TI - Lipid-lowering agents and fibrinolysis: lack of effect in vitro. PMID- 11788003 TI - Viral load versus p24 antigenaemia in human immunodeficiency virus infected patients. PMID- 11788004 TI - Cardiovascular risk: its assessment in clinical practice. AB - Cardiovascular disease is one of the major causes of mortality and morbidity in Western industrialised countries. Many factors impact on the likelihood of an individual suffering a stroke or heart attack. One of the greatest challenges facing clinicians today is how best to identify those individuals at increased risk, to prevent them becoming tomorrow's patients. Risk assessment tools can provide useful frameworks to support the identification of individuals who may benefit from therapeutic intervention; however, such tools should be used with care, as they do not include all the factors that contribute to future disease risk, and they are subject to an age bias. Nonetheless, they provide a systematic, evidence-based approach to the delivery of preventative healthcare services. PMID- 11788005 TI - Blastocystis hominis. PMID- 11788006 TI - Identification of Streptococcus pneumoniae strains. PMID- 11788007 TI - Human leucocyte antigen matching and cadaver renal transplantation in India. PMID- 11788009 TI - Decreased cannabinoid CB1 receptor mRNA levels and immunoreactivity in pituitary hyperplasia induced by prolonged exposure to estrogens. AB - Recent studies have demonstrated that cannabinoid CB1 receptor gene expression in the anterior pituitary gland is under the influence of estrogens. Because these receptors have been recently involved in the development of several types of cancer, it would be interesting to examine the changes produced in these receptors by the development of pituitary hyperplasia after a chronic exposure to estrogens. To this end, we measured mRNA levels and immunoreactivity for the CB1 receptor in the anterior pituitary gland of rats implanted with silastic capsules containing diethylstilbestrod (DES), a synthetic estrogen, or empty capsules. Results were as follows. Induction of pituitary hyperplasia with DES produced the expected body weight loss (-38.4%) and increase in pituitary weight (5-fold) and plasma prolactin (PRL) levels (90-fold). In hyperplastic pituitaries, both CB1 receptor mRNA levels and immunoreactivity decreased significantly (-79.4% and 63.2% respectively). Double immuno-labelling studies demonstrated that CB1 receptors colocalized, in hyperplastic pituitaries, with PRL- or luteinizing hormone-containing cells, as they did in normal pituitaries. In summary, estrogen induced pituitary hyperplastia was associated with a marked reduction in CB1 receptors, despite the fact that these receptors were located, among others, on lactotroph cells which develop hyperplasia during DES exposure. Whether this decrease is involved in the ethiology of pituitary hyperplasia and whether the pharmacological activation of these receptors might affect this process are presently unknown, but this will be subjected of further research. PMID- 11788008 TI - Leptin signal transduction in the HP75 human pituitary cell line. AB - Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OBR). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS 3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary. PMID- 11788010 TI - Hepatolithiasis (intrahepatic stone) during octreotide therapy for acromegaly: a case report. AB - We report a case of hepatolithiasis (intrahepatic stone) complicated by gram negative sepsis in a 37 year old male with acromegaly being treated with octreotide. As a child, he had suffered a traumatic injury to his liver requiring the surgical repair of a laceration. This is the first reported case of hepatolithiasis during octreotide therapy. Gallstones and bile sludge are common side effects of octreotide therapy but rarely become symptomatic or require treatment. Hepatolithiasis is uncommon in western countries but is quite prevalent in East Asia and is often associated with a predisposing condition that causes intrahepatic bile stasis (eg. bile duct stricture). In addition to its known effect on gallbladder stasis, octreotide alters bile acid composition and may thus hasten intrahepatic sludge and stone formation. Extra caution should be taken in using octreotide or its long-acting analog in patients otherwise predisposed to intrahepatic bile stasis. PMID- 11788011 TI - Lanreotide 60 mg, a longer-acting somatostatin analog: tumor shrinkage and hormonal normalization in acromegaly. AB - BACKGROUND: Somatostatin analogues are nowadays the milestone in the medical treatment of acromegaly. We evaluated the effects of a new 60 mg longer-acting formulation of lanreotide (LAN60) on GH/IGF-I levels and tumor size. PATIENTS: Twenty-one acromegalics entered a prospective monocentric open study. Eight were consecutive "de novo" patients (group I). Thirteen patients sensitive to SA (GH levels < 2.5 [mgr]g/l and/or IGF-I normalization on chronic LAN 30 mg (LAN30) treatment) were switched to LAN60 (group II). PROTOCOL: LAN60 was administered IM for 6 cycles at 28 day intervals. In group I when GH/IGF-I remained pathological, the intervals were shortened to 21 days for the last three cycles. CONTROLS: GH/IGF-I at the end of the 1st, 3rd and 6th cycle; MRI at the end of the study in all patients in group I bearing an adenoma. RESULTS: Group I. GH (p = 0.00638, below 2.5 [mgr]g/l in two patients) and IGF-I (p = 0.0289, normalized in 5) significantly decreased. In one of two patients shortening the LAN60 schedule was more effective in suppressing GH/IGF-I. Group II. No change in GH and IGF-I levels was observed with the administration of LAN60, instead of LAN30. On LAN60 GH remained below 2.5 [mgr]g/l in 8/10 patients and IGF-I normal in 11/11 patients that had attained those values on LAN30. Tumor markedly shrank (23% to 64% vs basal), from 1400 (664-1680) mm3 to 520 (500-960) mm3 (median, interquartile, p = 0.0218) in all the 5 evaluable patients. CONCLUSION: LAN60 is a very effective and longer-lasting formulation for the treatment of acromegaly. A closer administration schedule might achieve greater efficacy. Its effectiveness in shrinking tumor opens new perspectives in the therapy of acromegaly. PMID- 11788012 TI - Quinagolide in the management of prolactinoma. AB - OBJECTIVE: This study reports a six year experience with quinagolide (CV205-502) in the treatment of 40 patients with hyperprolactinemia or prolactinoma. PATIENTS AND MEASUREMENTS: Forty patients with hyperprolactinemia were treated with quinagolide (CV 205-502, Norprolac) for 2-72 months (mean 31.6 months). The patient's ages ranged from 12 to 53 years and 90% were female. Seventeen had no radiologic evidence of tumor; 11 had microadenomas; and 12 had macroadenomas. RESULTS: All patients had a reduction of the serum prolactin following quinagolide therapy with normalization in 82% with no tumor, 73% with microadenomas, and 67% with macroadenomas. Fifty-five percent of microadenoma and 75% of macroadenoma patients had a decrease in tumor size when assessed by a blinded reviewer. Ten of 38 female patients became pregnant while taking quinagolide. The dosage of quinagolide ranged from 75 to 400 [mgr]g/day with a median dose of 100[mgr]g/day. A comparison of side effects in a subgroup of 35 patients who had taken bromocriptine prior to quinagolide administration showed a greater than 75% reduction in nausea, vomiting, dizziness, and drowsiness during quinagolide administration. CONCLUSIONS: We conclude that quinagolide is a safe and effective long-term alternative to bromocriptine therapy, particularly in those individuals with bromocriptine intolerance. PMID- 11788014 TI - Intra-sellar salivary gland-like pleomorphic adenoma arising within the wall of a Rathke's cleft cyst. AB - Salivary gland rests occur in the posterior lobe of the pituitary gland near or often communicating with the Rathke's cleft or its cystic subdivisions, and are usually incidental autopsy findings. They are attributed to the oropharyngeal development of the Rathke's pouch and may rarely give rise to salivary gland-like tumors in the sella. We present a pleomorphic adenoma, a rare tumor of the sellar region, that has not been previously recognized in association with Rathke's cleft cyst. It occurred in a 44-year-old man who presented with hypopituitarism and reduced vision. Magnetic resonance imaging showed a sellar mass with suprasellar extension which was totally removed. It consisted of segments of a cyst wall lined by focally ciliated columnar of cuboid epithelium containing goblet cells. An eosinophilic granular material with cholesterol clefts represented the contents of the cyst. Within its wall there was a tumor with ductal structures and non-ductal varied cellular components including hypercellular areas of spindle and ovoid cells forming interlacing fascicles. Individual cells appeared to float in abundant mucinous material. The appearances were those of a salivary gland pleomorphic adenoma arising within the wall of a Rathke's cleft cyst. The myoepithelial nature of non-ductal tumor cells was confirmed with immunocytochemistry. The existence of seromucous glands communicating with the Rathke's cleft remnants, explains the concomitant occurrence of the tumor and the cyst. This rare neoplasm from salivary gland rest should be considered in the differential diagnosis of unusual sellar and suprasellar tumors. PMID- 11788015 TI - Scientific misconduct. PMID- 11788013 TI - Pergolide as primary therapy for macroprolactinomas. AB - The objective of this study is to determine whether pergolide therapy is an effective modality for the de novo treatment of patients with macroprolactinomas. Twenty-two consecutive patients with macroprolactinomas were included in the study and followed prospectively. These included 16 men and 6 women in whom pregnancy was not of concern. Pergolide was administered once or twice a day depending on the patient's preference. Ten patients received 0.1 mg daily as a maintenance regimen and in the others the daily dose ranged from 0.05 to 0.5 mg. Eight patients reported minor but tolerable side effects. One patient had to be switched to cabergoline because of intolerable nausea. After a mean of 12 months (range, 3-36), mean PRL levels declined from 3,135 ng/ml (range, 126-31,513) to 50 ng/ml (3-573), representing a mean PRL suppression of 88% (range, 0-99). PRL levels became normal in 15 patients and decreased to 25-40 ng/ml in 3 others. The mean tumor volume shrinkage was 25% or greater in 19 patients (86%), 50% or greater in 17 patients (77%), and 75% or greater in 10 patients (45%). Visual abnormalities were reversible after pergolide therapy in all but 1 of 12 patients with initially abnormal formal visual testing. Two out of 4 premenopausal women did not normalize PRL levels and had persistent oligomenorrhea. Testosterone was low in 14 men at presentation and normalized in 3 with pergolide therapy. We conclude that pergolide is a safe, inexpensive, and generally well-tolerated dopamine agonist for the treatment of macroprolactinomas in men and women in whom pregnancy is not of concern. In these specific populations, pergolide may become the first-line therapy for treatment of macroprolactinomas. PMID- 11788016 TI - Acute postoperative pain management: a review. AB - A high standard of acute postoperative pain control is achievable, using a comprehensive multimodal approach, resulting in improved patient outcomes. Unfortunately, for the majority of surgical patients, this is not achieved, with significant negative consequences. The purpose of this review is to identify the barriers that exist to achieving optimal postoperative pain control. Current approaches to pain management will be discussed. Solutions to lower these barriers will be suggested. PMID- 11788017 TI - Reliability of the pediatric dysfunctional voiding symptom score in monitoring response to behavioral modification. AB - PURPOSE: We previously evaluated the performance of a newly devised dysfunctional voiding symptom score to quantify abnormal voiding behaviors in children. The symptom score ranges from 0 to 30 with higher scores indicating greater severity. In this study, we test the performance of the symptom score in monitoring effectiveness and compliance with a program of behavioral modification. MATERIALS AND METHODS: One hundred four patients (age 3-10 years) were clinically diagnosed as having dysfunctional voiding (DV). At initial visit, after their baseline DV symptom scores were tabulated, they were introduced to a program of behavioral modification that included both verbal and written instructions. After an average follow up of 5 months, all families were mailed questionnaires to: a) assess whether the child was compliant with bladder retraining, and b) request the completion of a second DV symptom-scoring sheet. The change in symptom score was correlated with treatment compliance. Statistical analysis of the data was done using non-parametric method (Mann-Whitney U test). RESULTS: Forty-eight out of 104 children (46%) completed the mailed questionnaires. Twenty-eight (Group A1) were compliant with the behavioral modification program, and the remaining 20 children (Group A2) were not compliant. Although the median score at initial evaluation was similar in both groups (15 versus 14.5 respectively), scores in last follow up were significantly lower in Group A1 than the initial scores (6 versus 14.5 respectively). The scores in last follow-up in Group A2 were not significantly different from their initial symptom scores (median 11 versus 14.5 respectively). CONCLUSION: The DV symptom score reliably and quantitatively reflects improvement in voiding symptoms in patients compliant with behavioral modification. Patients non-compliant with a bladder retraining program may be identified by lack of decrease in their DV symptom score. Key Words: voiding dysfunction, pediatric, behavioral modification, symptom score PMID- 11788018 TI - Immediate versus delayed outpatient flexible cystoscopy: final report of a randomized study. AB - PURPOSE: To evaluate discomfort experienced by men undergoing an immediate versus delayed outpatient flexible cystoscopy after topical local anesthesia. PATIENTS AND METHODS: Two hundred eighty eight consecutive men with superficial bladder tumors were randomized to undergo immediate or delayed surveillance flexible cystoscopy after intraurethral instillation of lidocaine jelly. The patients recorded their level of pain experienced during cystoscopy on a 4-point pain scale and on a 10-point visual analogue (VAS) scale. RESULTS: Of the 288 patients, 145 underwent immediate cystoscopy and 143 had a delayed cystoscopy. The mean pain score on a scale of 1 (no pain) to 4 (severe pain) was 1.6 after immediate cystoscopy compared with 1.5 after delayed cystoscopy (p=7). The mean VAS score on a scale of 1 (no pain) to 10 (most painful) was 1.8 after immediate cystoscopy versus 1.7 after delayed cystoscopy (p=5). CONCLUSION: There was no difference in pain perception among men undergoing an immediate or a delayed outpatient flexible cystoscopy using the same local anesthetic. PMID- 11788019 TI - Inflammatory pseudotumor of the urinary bladder: a report of five cases and review of the literature. AB - We describe five patients who recently presented with gross hematuria secondary to inflammatory pseudotumors of the bladder along with a review of the literature. At presentation, four of the five patients were clinically misdiagnosed as malignancies of which two were further believed to be leiomyosarcomas on initial histological examination because of their spindle-cell appearance. Conservative excision either by transurethral resection or partial cystectomy was curative in all cases. The main importance of these rare, benign lesions is to differentiate them from malignant tumors for which they may be mistaken, thus avoiding radical surgery and its attendant complications. PMID- 11788020 TI - HIV-specific IgG in cervicovaginal secretions of exposed HIV-uninfected female sexual partners of HIV-infected men. AB - The presence of human immunodeficiency virus (HIV)-specific antibodies was examined in plasma and cervicovaginal (mucosal) samples of 24 HIV-exposed uninfected (EU) female sexual partners of HIV-infected men, and compared with findings in 18 HIV-infected and 15 low-risk HIV-uninfected women. Only HIV infected women had detectable HIV-specific immunoglobulin G (IgG) (18 of 18) or HIV-IgA (6 of 18) in cervicovaginal samples by enzyme immunoassay (EIA). However, 3 of 24 EU women had positive Western blot (WB) for HIV-IgG in cervicovaginal secretions, while 2 of 24 EU women and 1 of 15 low-risk controls had indeterminate IgG-WB. EU women with positive or indeterminate IgG-WB in the cervicovaginal samples were similar in risk to the remaining EU women. None of the HIV-uninfected women had mucosal HIV-IgA. The findings suggest that some sexually or parenterally exposed HIV-uninfected women might develop low-level mucosal IgG responses. However, it appears unlikely that HIV-specific cervicovaginal antibodies play a major role in protection from HIV infection in this EU population. PMID- 11788021 TI - Human immunodeficiency virus in semen and plasma: investigation of sexual transmission risk behavioral correlates. AB - Risks for sexually transmitted HIV may be related to concentrations of virus detected in semen and previous research shows a small to moderate association between viral load in blood and semen. This study examined the association between viral load in semen and plasma in a community sample of HIV-infected men and is the first study to examine semen viral load in relation to sexual transmission risk behaviors. A sample of 44 HIV-positive men recruited from community service agencies provided semen, blood, and urine samples and completed clinical interviews assessing health and behavior. We failed to find an association between viral load in semen and plasma, Spearman rho = 0.07, p > 0.1. When restricted to participants with detectable virus in semen and plasma, the correlation remained nonsignificant, rho = -0.16, p > 0.1. Men who had higher semen viral loads relative to their plasma viral load were distinguished by having engaged in significantly higher rates of unprotected intercourse as the insertive sex partner in the previous 3 months. Semen viral load was not, however, related to recent or current sexually transmitted infections (STIs). This study is among the first to examine sexual transmission risk behaviors as marker for HIV infectiousness. Results caution against inferring sexual transmission infectiousness based on plasma viral load and suggest that HIV positive men who practice higher rates of insertive intercourse may be more infectious even in the absence of other STIs. PMID- 11788022 TI - Resistance to neutralizing antibody and expanded coreceptor usage are associated with human immunodeficiency virus type 1 isolates derived from chimpanzees with pathogenic infections. AB - Immunologic and biologic factors associated with the progression to AIDS in HIV-1 infected chimpanzees were investigated. Chimpanzee C499 was euthanized in 1996 as a result of the development of AIDS approximately 11 years after infection with HIV-1. At the time of initial disease development (September 1995), blood from this animal was transfused to an uninfected chimpanzee, C455, resulting in a rapid loss of CD4(+) T cells. Virus isolates were derived from both animals and termed HIV-1(JC) (derived from C499 at the time of disease development; JC isolate) and HIV-1(NC) (derived from C455 1 month posttransfusion; NC isolate). In vitro studies demonstrate that the parental viruses used to inoculate C499 were susceptible to neutralization by serum from that animal. In contrast, serum from C499 at any time was unable to neutralize the JC or NC isolates. Similarly, the JC and NC isolates were highly resistant to neutralization by serum from C455. However, serum from C455 was also unable to neutralize either of the parental viruses or any of the normally neutralization sensitive isolates tested. Serum samples from the two additional chimpanzees that were inoculated with the NC isolate were also unable to neutralize these isolates. Coreceptor usage of the uncloned JC and NC isolates was somewhat expanded when compared with that of LAV1b and SF2. However, molecular clones derived from the JC and NC isolates (JC16 and NC7) displayed only a limited coreceptor repertoire despite having unique V3 loop sequences. The results suggest that the JC and NC isolates are neutralization escape mutants and display a different phenotype than the parental strains LAV1b and SF2. PMID- 11788023 TI - Development of a safe and rapid neutralization assay using murine leukemia virus pseudotyped with HIV type 1 envelope glycoprotein lacking the cytoplasmic domain. AB - Neutralizing antibody (NAb) is a critical component of an immune system that can potentially provide sterilizing protection against human immunodeficiency virus type 1 (HIV-1). Therefore, an in vitro assay that can rapidly, safely, and accurately evaluate the NAb response vaccine candidates elicit, especially against a large number of HIV-1 variants, would be highly valuable. It has been demonstrated that HIV-1 envelope glycoprotein lacking the cytoplasmic domain can pseudotype murine leukemia virus encoding the beta-galactosidase gene and that this pseudovirus can specifically infect CD4(+) cells (Schnierle BS, Stitz J, Bosch V, et al.: Proc Natl Acad Sci USA 1997;94:8640-8645). Because the pseudovirus is not biohazardous and because the infection can be quantitatively determined within 2 days, we examined the feasibility of using the pseudovirus for high-throughput neutralization assays for HIV-1. We have generated viruses pseudotyped with gp140 of six different HIV-1 isolates (LAI, RF, Bal, AD8, 89.6, and DH12). All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4. More importantly, the neutralization sensitivity profile of these pseudoviruses was virtually identical to that observed from more conventional neutralization assays using either HIV-1 or SHIV. All pseudoviruses could be neutralized by broadly reactive human monoclonal antibody IgG1 b12. Our results indicate that the pseudoviruses are ideal for high-throughput evaluation of immune sera for their capacity to broadly neutralize a large number of HIV-1 isolates. PMID- 11788024 TI - Biological characterization of HIV type 1 envelope V3 regions from mothers and infants associated with perinatal transmission. AB - Our previous study has shown that the human immunodeficiency virus type 1 (HIV-1) envelope V3 region minor genotypes of infected mothers were transmitted to their infants and predominated initially as a homogeneous virus population in the infants (Ahmad N, Baroudy BM, Baker RC, et al.: J Virol 1995;69:1001-1012). Here we have characterized the biological properties, including cellular tropism, replication efficiency, cytopathic effects, and coreceptor utilization, of these V3 region isolates from mothers and infants. Nineteen V3 region sequences from three mother-infant pairs, including the minor variants of mothers and the major variants of infants as characterized in our previous study, were reciprocally inserted into an HIV-1 infectious molecular clone, pNL4-3, and chimeric viruses were generated by DNA transfections into HeLa cells. Equal amounts of chimeric viruses were then used to infect T lymphocyte cell lines (A3.01 and MT-2), primary blood lymphocytes (PBLs), primary monocyte-derived macrophages (MDMs), and coreceptor cell lines. We found that the V3 region chimeras failed to replicate in T lymphocyte cell lines but replicated in MDMs and PBLs, albeit at reduced levels compared with R5 laboratory HIV-1 strains. In addition, the V3 region chimeras were able to infect the HOS-CD4(+)CCR5(+) cell line, suggesting CCR5 coreceptor utilization. Moreover, the V3 region chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium-inducing (NSI) phenotypes. In conclusion, the HIV-1 minor genotypes of infected mothers with macrophage-tropic and NSI or R5 phenotypes are transmitted to their infants and are initially maintained with the same properties. PMID- 11788025 TI - V3-specific polyclonal antibodies affinity purified from sera of infected humans effectively neutralize primary isolates of human immunodeficiency virus type 1. AB - Although many human sera possess potent neutralizing activities for primary HIV-1 viruses, such activities are not efficiently induced by the current generation of vaccine candidates, and the epitopes mediating this neutralization are not known. The V3 loop of gp120 is believed to be the principal neutralization domain of laboratory-adapted viruses, but the importance of this region in neutralization of primary isolates is unclear. This question was explored using polyclonal anti V3 antibodies purified by immunoaffinity methods from sera of HIV-1-infected patients. To include antibodies that might be directed against conformational and/or glycan-dependent epitopes not presented by synthetic peptides, the antibody isolations were performed with a fusion glycoprotein expressing the native V3 region of JR-CSF, a primary R5 isolate. V3-reactive antibody fractions from all eight sera examined showed potent neutralization of at least one of the three primary HIV-1 isolates tested; four of these antibody preparations neutralized all three primary viruses. For a number of serum-virus combinations 90% neutralization doses (ND(90)) between 1 and 5 microg/ml were obtained, and the most potent anti-V3 fraction had ND(50) values at or below 0.3 microg/ml for all three primary isolates. These neutralization activities against primary viruses were higher than those of potent monoclonal antibodies assayed in the same experiment. These data indicate that the V3 region can be an important neutralization target in primary isolates, and suggest that effective presentation of V3 epitopes in a vaccine formulation might induce protective humoral responses against natural infection by HIV-1. PMID- 11788026 TI - Sustained cytomegalovirus-specific CD4+ T cell response associated with prevention of recurrence of cytomegalovirus retinitis without secondary prophylaxis after highly active antiretroviral therapy in patients with AIDS. AB - It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS. PMID- 11788027 TI - A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AB - We have established a panel of human monoclonal antibodies against human immunodeficiency virus type 1 (HIV-1). The antibodies 2F5 and 2G12 have been identified to be two of the most potently in vitro neutralizing antibodies against HIV-1. Here we report on a further antibody, 4E10, of similar in vitro neutralizing potency. 4E10 binds to a novel epitope C terminal of the ELDKWA sequence recognized by 2F5, which has been so far the only described broadly neutralizing anti-gp41 antibody. Both 4E10 and 2F5 bind only weakly to infected cells compared with gp120-specific 2G12 and polyclonal anti-HIV-1 immunoglobulin (HIVIG), but show potent in vitro neutralizing properties. 4E10 neutralizes potently not only tissue culture-adapted strains but also primary isolates of different clades, including A, B, C, D, and E. Viruses that were found to be resistant to 2F5 were neutralized by 4E10 and vice versa; none of the tested isolates was resistant to both anti-gp41 antibodies. This confirms that the region recognized by 2F5 and 4E10 is essential for viral infectivity and may be important for vaccine design. Moreover, our results suggest that 4E10 should be further investigated for passive anti-HIV immunotherapy. PMID- 11788028 TI - Feline immunodeficiency virus Gag- and Env-specific immune responses after vaginal versus intravenous infection. AB - To better understand the correlation of mucosal and systemic immune responses with lentiviral containment, we contrasted the early mucosal and systemic immune responses induced by vaginal versus intravenous exposure of cats to feline immunodeficiency virus (FIV) isolates of differing pathogenicity and clade (i.e., FIV-B-2542 and FIV-A-PPR). We found that despite divergence in viral genotype, the mucosal and systemic immune responses induced differed more with route of exposure than virus isolate. In intravenously exposed cats, Gag-specific antibody (both IgG and IgA isotype) predominated in the serum, saliva, and vaginal wash fluid irrespective of infecting virus isolate. While Env-specific responses were more variable, they were more often detected in vaginally infected cats. Both IgG and IgA directed against Gag and Env were consistently present in vaginal wash fluids independent of route of infection or virus isolate. FIV Gag- and Env specific cytotoxic lymphocytes (CTLs) were detected in blood and tissue lymphocytes of cats infected with either virus strain but were greatest in intravenously infected animals. Likewise, FIV-specific CTLs were detected in CD8(+) vaginal lymphocytes of animals infected by either route but were also more frequent in intravenously inoculated animals. In summary, we found qualitative differences in the immune responses following vaginal infection but no evidence (1) that mucosal immune responses were enhanced in vaginally exposed cats, (2) that local mucosal infection led to measurably greater immune responses in either compartment; or (3) that more prominent immune responses correlated with lower viral burden. PMID- 11788029 TI - Dual chemical sequestration: a key mechanism in transitions among ecological specialization. AB - Platyphora leaf beetles form a vast group of tropical species each feeding on a restricted set of host plants and exhibiting bright coloration warning predators against their chemical protection. These beetles offer an exceptional opportunity for understanding the evolution of phytochemical sequestration. Indeed, qualitative studies of defensive secretions indicate that Platyphora species acquire toxicity via sequestration of plant secondary metabolites. All produce pentacyclic triterpene saponins from sequestered plant amyrins, but our analyses also indicate that many Platyphora species produce a dual chemical defence, that is, they are additionally protected by lycopsamine-type pyrolyzidine alkaloids that they also sequester from their host. This paper reports on the evolution of chemical defence and host affiliation in Platyphora leaf beetles as reconstructed on a molecular phylogeny of mitochondrial and nuclear DNA sequences. The analyses indicate that dual sequestration could be the key mechanistic means by which transitions among ecological specializations (i.e. restricted host-plant affiliations) are made possible. PMID- 11788030 TI - Limited-view iridescence in the butterfly Ancyluris meliboeus. AB - Few mechanisms exist in nature that effect colour reflectivity, simultaneously high in spectral purity and in intensity, over a strictly limited portion of solid angle above a surface. Fewer still bring about such colour reflectivity with an angle dependence that is distinct from the colour transition associated with conventional multilayer interference. We have discovered that the ventral wings of the butterfly Ancyluris meliboeus exhibit these optical effects, and that they result from remarkable nano-scale architecture on the wing scales of the butterfly. This nano-structure is in the form of high-tilt multilayering that, as a result of abrupt termination of the multilayers, brings about diffraction concurrently with interference. The product is bright structural colour in a limited angular region over the ventral wing surface that enables remarkably strong flicker and colour contrast through minimal wing movement. The visibility effects associated with its colour, in terms of bright and dark zones of the observation hemisphere over the wing surface, are described. We suggest the purpose of the high-contrast ventral wing visibility associated with A. meliboeus is at-rest signalling; this is distinct from the dorsal wing visibility of other species such as those of the genus Morpho, the function of which is largely for in-flight signalling. PMID- 11788031 TI - Temperature effects on energy metabolism: a dynamic system analysis. AB - Q(10) factors are widely used as indicators of the magnitude of temperature induced changes in physico-chemical and physiological rates. However, there is a long-standing debate concerning the extent to which Q(10) values can be used to derive conclusions about energy metabolism regulatory control. The main point of this disagreement is whether or not it is fair to use concepts derived from molecular theory in the integrative physiological responses of living organisms. We address this debate using a dynamic systems theory, and analyse the behaviour of a model at the organismal level. It is shown that typical Q(10) values cannot be used unambiguously to deduce metabolic rate regulatory control. Analytical constraints emerge due to the more formal and precise equation used to compute Q(10), derived from a reference system composed from the metabolic rate and the Q(10). Such an equation has more than one unknown variable and thus is unsolvable. This problem disappears only if the Q(10) is assumed to be a known parameter. Therefore, it is concluded that typical Q(10) calculations are inappropriate for addressing questions about the regulatory control of a metabolism unless the Q(10) values are considered to be true parameters whose values are known beforehand. We offer mathematical tools to analyse the regulatory control of a metabolism for those who are willing to accept such an assumption. PMID- 11788032 TI - Pheasant sexual ornaments reflect nutritional conditions during early growth. AB - Differences in growth conditions during early life have been suggested to cause long-lasting effects on morphology and quality of adult birds. We experimentally investigated the effect of early growth conditions on the expression of sexual ornaments later in life in male ring-necked pheasants (Phasianus colchicus). We also investigated the effects on immune function, as it could be a functional link between early nutrition and ornament expression. We manipulated the dietary protein intake during the first eight weeks post hatching. Males receiving fodder with 27% protein during the first three weeks of life grew larger and more colourful wattles when sexually mature than males receiving a low-protein diet (20.5% protein). Spur length was unaffected by diet treatment. Manipulation of food protein levels during weeks 4-8 after hatching had no effect on the development of ornaments. The different protein treatments had no long-term effect on either humoral or cell-mediated immune responses. There was, however, a positive relationship between spur length and cell-mediated immune responsiveness. Our study shows that expression of a sexual ornament in adult pheasants reflects nutritional conditions early in life. Because the expression of secondary sexual ornaments is affected by conditions during early growth, by selecting more ornamented males, females would choose mates that are superior at handling early nutritional stress. If the susceptibility to early nutritional stress also has a hereditary basis, females may benefit by obtaining 'good genes'. PMID- 11788033 TI - Carotenoids and egg quality in the lesser blackbacked gull Larus fuscus: a supplemental feeding study of maternal effects. AB - Egg quality is a phenotype of, and can profoundly influence fitness in, both mother and offspring. However, the physiological mechanisms that underlie this maternal effect are poorly understood. Carotenoids are hypothesized to enhance antioxidant activity and immune function, and are responsible for the pigmentation of egg yolk. The proximate basis and consequences of this maternal investment, however, have not previously been studied in wild birds. In this supplemental feeding study of lesser black-backed gulls, Larus fuscus, carotenoid fed females are shown to have increased integument pigmentation, higher plasma concentrations of carotenoids and antioxidant activity, and lower plasma concentrations of immunoglobulins (Igs) in comparison with controls. In turn, carotenoid-fed females produced eggs containing high carotenoid but low Ig concentrations (i.e. passive immunity), whereas control females produced eggs containing low carotenoid but high Ig concentrations. Within-clutch patterns of these resources varied over the laying sequence in a similar manner in both carotenoid-fed and control nests. Our results suggest that carotenoids could be one resource responsible for egg quality maternal effects in birds. We discuss the possible implications of carotenoid-mediated effects on phenotype for fitness in mothers and their offspring. PMID- 11788034 TI - Clade-specific morphological diversification and adaptive radiation in Hawaiian songbirds. AB - The Hawaiian honeycreepers are a dramatic example of adaptive radiation but contrast with the four other songbird lineages that successfully colonized the Hawaiian archipelago and failed to undergo similar diversification. To explore the processes that produced the diversity dichotomy in this insular fauna, we compared clade age and morphological diversity between the speciose honeycreepers and the comparatively depauperate Hawaiian thrushes. Mitochondrial-DNA-based genetic distances between these Hawaiian clades and their continental sister taxa indicate that the ancestral thrush colonized the Hawaiian Islands as early as the common ancestor of the honeycreepers. This similar timing of colonization indicates that the marked difference in diversity between the Hawaiian honeycreeper and thrush clades is unlikely to result from differences in these clades' tenures within the archipelago. If time cannot explain the contrasting diversities of these taxa, then an intrinsic, clade-specific trait may have fostered the honeycreeper radiation. As the honeycreepers have diversified most dramatically in morphological characters related to resource utilization, we used principal components analyses of bill characters to compare the magnitudes of morphological variation in the ancestral clades from which the Hawaiian honeycreeper and thrush lineages are derived, the Carduelini and Turdinae respectively. Although the Carduelini share a more recent common ancestor and have a lower species diversity than the Turdinae, these finch-like relatives of the honeycreepers exhibit significantly greater variation in bill morphology than do the continental relatives of the Hawaiian thrushes. The higher magnitude of morphological variation in the non-Hawaiian Carduelini suggests that the honeycreepers fall within a clade exhibiting a generally high evolutionary flexibility in bill morphology. Accordingly, although the magnitude of bill variation among the honeycreepers is similar to that of the entire passerine radiation, this dramatic morphological radiation represents an extreme manifestation of a general clade-specific ability to evolve novel morphologies. PMID- 11788035 TI - Relationships fade with time: a meta-analysis of temporal trends in publication in ecology and evolution. AB - Both significant positive and negative relationships between the magnitude of research findings (their 'effect size') and their year of publication have been reported in a few areas of biology. These trends have been attributed to Kuhnian paradigm shifts, scientific fads and bias in the choice of study systems. Here we test whether or not these isolated cases reflect a more general trend. We examined the relationship using effect sizes extracted from 44 peer-reviewed meta analyses covering a wide range of topics in ecological and evolutionary biology. On average, there was a small but significant decline in effect size with year of publication. For the original empirical studies there was also a significant decrease in effect size as sample size increased. However, the effect of year of publication remained even after we controlled for sampling effort. Although these results have several possible explanations, it is suggested that a publication bias against non-significant or weaker findings offers the most parsimonious explanation. As in the medical sciences, non-significant results may take longer to publish and studies with both small sample sizes and non-significant results may be less likely to be published. PMID- 11788036 TI - Density-dependent growth as a key mechanism in the regulation of fish populations: evidence from among-population comparisons. AB - It is generally assumed that fish populations are regulated primarily in the juvenile (pre-recruit) phase of the life cycle, although density dependence in growth and reproductive parameters within the recruited phase has been widely reported. Here we present evidence to suggest that density-dependent growth in the recruited phase is a key process in the regulation of many fish populations. We analyse 16 fish populations with long-term records of size-at-age and biomass data, and detect significant density-dependent growth in nine. Among-population comparisons show a close, inverse relationship between the estimated decline in asymptotic length per unit biomass density, and the long-term average biomass density of populations. A simple population model demonstrates that regulation by density-dependent growth alone is sufficient to generate the observed relationship. Density-dependent growth should be accounted for in fisheries' assessments, and the empirical relationship established here can provide indicative estimates of the density-dependent growth parameter where population specific data are lacking. PMID- 11788037 TI - Invasion of vacant niches and subsequent sympatric speciation. AB - An individual-based simulation study was conducted to examine the population dynamics of 'invasion of a vacant niche' and subsequent speciation (by reproductive isolation) when food resources are randomly distributed spatially within the habitat and the frequencies of different food types are bimodally distributed (i.e. smaller and larger sizes of food being most abundant). The initially vacant niche was that of unused larger sizes of food. When phenotypic variation for resource use (i.e. food sizes) was small in the initial population, and each female could choose a mate from anywhere in the habitat, the population could not invade the vacant niche. But when the dispersal distance of the offspring and the area within which a female could choose a mate were small (i.e. the genetic neighbourhood size was small), the population could, in most cases, evolve to use both smaller and larger food sizes and form sister species sympatrically, with each species utilizing one of the two niches (small and large sizes of food). When phenotypic variation in resource use in the initial population was large, the population could, in most cases, invade the vacant niche by evolving to use both smaller and larger sizes of food. The probability of speciation increased as the dispersal distance of offspring decreased. The results indicate that populations whose individuals have small Wright's genetic neighbourhoods may often exploit a vacant niche and diversify sympatrically in the process. PMID- 11788038 TI - A rapid fish radiation associated with the last sea-level changes in southern Brazil: the silverside Odontesthes perugiae complex. AB - Coastal freshwater fishes provide valuable models for studying the role of the last glaciations in promoting speciation. To date, the great majority of studies are of Northern Hemisphere taxa, and reflect the influence of vicariant events during, or prior to, the Pleistocene. Microsatellite markers and mitochondrial DNA sequences were used to investigate patterns of population divergence and evolutionary relationships in a freshwater group of silverside fishes (Odontesthes perugiae complex), endemic to the recently formed coastal plain of southern Brazil. Lacustrine morphotypes showed concordant patterns of genetic and morphological divergence consistent with the geographical history of the coastal plain. The results support the proposal of a silverside radiation chronologically shaped by the sea-level changes of the Pleistocene and Holocene. The radiating lineage comprises a minimum of three allopatric and two sympatric lacustrine species. Four species displayed extremely high levels of genetic variation and some of the most rapid speciation rates reported in fishes. These features were related to a marine-estuarine origin of the radiation. To the best of our knowledge, this study represents the first molecular phylogeographic survey of a coastal radiation in South America. PMID- 11788039 TI - Guanine-type retinal tapetum and ganglion cell topography in the retina of a carangid fish, Kaiwarinus equula. AB - A guanine-type retinal tapetum was recorded in the eyes of a carangid fish Kaiwarinus equula (= Carangoides equula), spectrophotometric evidence of such being presented. The total amount of guanine in one eye was about 6.5 mg, the guanine density being ca. 1.3 mg cm(-2) over the retinal surface area. To examine the guanine distribution within the retina, the latter was divided into 21 regions. An area of high guanine density (more than 2.0 mg cm(-2)) was observed in the dorsal fundus of the retina, suggesting that the most sensitive vision was checked downward. Using whole-mount retinal preparations, the distribution of Nissl-stained cells within the retinal ganglion cell layer was examined. The greatest cell density area (area centralis) was observed only in the temporal retina. The visual acuity of the area centralis was 4.3 cycles deg(-1), suggesting that high resolution and binocular vision were directed frontally in this species. The eyes of a related carangid (Pseudocaranx dentex), lacking a tapetum, were also examined for comparison. The possible ecological advantage resulting from the tapetum is discussed in terms of visual threshold. PMID- 11788040 TI - Feeding in extinct jawless heterostracan fishes and testing scenarios of early vertebrate evolution. AB - How long-extinct jawless fishes fed is poorly understood, yet interpretations of feeding are an important component of many hypotheses concerning the origin and early evolution of vertebrates. Heterostracans were the most diverse clade of armoured jawless vertebrates (stem gnathostomes), and the structure of the mouth and its use in feeding are the subjects of long-standing and heated controversy. I present here evidence that heterostracan feeding structures exhibit recurrent patterns of in vivo wear, are covered internally by microscopic oral denticles, and that the mouth may have been less flexible than has been thought. These data, particularly the absence of wear at the tips of oral plates, and the evidence that the mouth was lined with delicate outwardly directed denticles, effectively falsify all but one hypothesis of feeding in heterostracans: heterostracans were microphagous suspension feeders. This has a direct bearing on hypotheses that address ecological aspects of early vertebrate diversity and evolution, contradicting the widespread view that the pattern of early vertebrate evolution reflects a long-term trend towards increasingly active and predatory habits. PMID- 11788041 TI - Tympanal and atympanal 'mouth-ears' in hawkmoths (Sphingidae). AB - The labral pilifers and the labial palps form ultrasound-sensitive hearing organs in species of two distantly related hawkmoth subtribes, the Choerocampina and the Acherontiina. Biomechanical examination now reveals that their ears represent different types of hearing organs. In hearing species of both subtribes, the labral pilifer picks up vibrations from specialized sound-receiving structures of the labial palp that are absent in non-hearing species. In Choerocampina, a thin area of cuticle serves as an auditory tympanum, whereas overlapping scales functionally replace a tympanum in Acherontiina that can hear. The tympanum of Choerocampina and the scale-plate of Acherontiina both vibrate maximally in response to ultrasonic, behaviourally relevant sounds, with the vibrations of the tympanum exceeding those of the scale plate by ca. 15 dB. This amplitude difference, however, is not reflected in the vibrations of the pilifers and the neural auditory sensitivity is similar in hearing species of both subtribes. Accordingly, morphologically different - tympanal and atympanal - but functionally equivalent hearing organs evolved independently and in parallel within a single family of moths. PMID- 11788042 TI - Coevolution of costly mate choice and condition-dependent display of good genes. AB - Females often choose their mates, instead of mating at random, even when a father contributes nothing but genes to his offspring. Costly female preferences for males with exaggerated traits that reduce viability, such as the peacock's tail, are particularly puzzling. Such preferences can evolve if directly favoured by natural selection or when the exaggerated trait, although maladaptive per se, indicates high overall quality of the male's genotype. Two recent analyses suggested that the advantage to mate choice based on genetic quality is too weak to explain extreme cases of exaggeration of display traits and the corresponding preferences. We studied coevolution of a female mate-preference function and a genotype-dependent male display function where mutation supplies variation in genotype quality and mate preference is costly. Preference readily evolves, often causing extreme exaggeration of the display. Mate choice and trait expression can approach an equilibrium, or a limit cycle, or exaggeration can proceed forever, eventually causing extinction. PMID- 11788044 TI - Alzheimer's disease: molecularly based immunotherapeutics. PMID- 11788045 TI - Immunotherapy with beta-amyloid for Alzheimer's disease: a new frontier. AB - Alzheimer's disease (AD) represents the fourth leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of finding a way to prevent the underlying brain pathology from progressing toward the inevitable conclusion of the disease. However, new immunotherapeutic approaches have been described that are based on vaccination with the beta-amyloid 1-42 peptide (Abeta). The encouraging efficacy and safety of Abeta immunization in reducing neuropathology in animal models of AD has opened up new therapeutic possibilities for patients. Immunization with Abeta is aimed at reducing the Abeta-associated pathology of AD. It is hypothesized that this approach will also reduce the cascade of downstream events leading to neuronal cell loss and, ultimately, dementia. The ensuing articles in this issue describe various aspects of the Abeta immunization strategy and their potential relevance to AD treatment. PMID- 11788046 TI - A gene expression profile of Alzheimer's disease. AB - Postmortem analysis of brains of patients with Alzheimer's disease (AD) has led to diverse theories about the causes of the pathology, suggesting that this complex disease involves multiple physiological changes. In an effort to better understand the variety and integration of these changes, we generated a gene expression profile for AD brain. Comparing affected and unaffected brain regions in nine controls and six AD cases, we showed that 118 of the 7050 sequences on a broadly representative cDNA microarray were differentially expressed in the amygdala and cingulate cortex, two regions affected early in the disease. The identity of these genes suggests the most prominent upregulated physiological correlates of pathology involve chronic inflammation, cell adhesion, cell proliferation, and protein synthesis (31 upregulated genes). Conversely, downregulated correlates of pathology involve signal transduction, energy metabolism, stress response, synaptic vesicle synthesis and function, calcium binding, and cytoskeleton (87 downregulated genes). The results support several separate theories of the causes of AD pathology, as well as add to the list of genes associated with AD. In addition, approximately 10 genes of unknown function were found to correlate with the pathology. PMID- 11788047 TI - Immunotherapeutic strategies for prevention and treatment of Alzheimer's disease. AB - Pathologic examination in Alzheimer's disease (AD) shows a significant correlation between beta-amyloid peptide (AbetaP) deposition and the clinical severity of dementia. Formation of beta-amyloid (Abeta) is a complex kinetic and thermodynamic process, dependent on peptide-peptide interactions that may be modulated by other proteins. We found that site-directed antibodies toward peptide EFRH sequences 3-6 of the N-terminal region of AbetaP suppress in vitro formation of Abeta and dissolve already-formed fibrillar amyloid. These so-called chaperone-like properties of monoclonal antibodies led to the development of a new immunologic approach to AD treatment. The immunization procedure, based on phages displaying the EFRH epitope as antigen, induced anti-AbetaP antibodies that recognized the whole AbetaP and exhibited antiaggregating properties similar to those of antibodies obtained by injection of Abeta fibrils. Production and performance of anti-beta-amyloid antibodies in the transgenic mouse model of AD showed that these antibodies may be delivered from the periphery to the central nervous system, preventing the formation of Abeta and dissolving already-present aggregates. Moreover, immunization with Abeta protected transgenic mice from the learning and age-related memory deficits that occur in AD. These data support the hypotheses that Abeta plays a central role in AD and that site-directed antibodies that modulate Abeta conformation may provide immunotherapy of the disease. PMID- 11788048 TI - Nasal vaccination with beta-amyloid peptide for the treatment of Alzheimer's disease. AB - Alzheimer's disease (AD) is a severe neurodegenerative disease for which there is currently no effective prevention or treatment. The prediction that the number of U.S. patients with AD will triple to approximately 14 million over the next 50 years underscores the urgent need to explore novel therapeutic strategies for AD. The beta-amyloid protein (Abeta) accumulation and accompanying inflammation appear to play key roles in initiating the neuronal degeneration that underlies the signs and symptoms of AD. Interventions geared toward reducing Abeta accumulation and inflammatory responses should delay or prevent the onset of the clinical disease. Recently, several research groups, including ours, have shown that vaccination with Abeta results in a significant lowering of the Abeta burden in the brains of APP transgenic mice and, in some studies, improvement in their cognitive deficits. Our study described a novel approach, namely mucosal (intranasal) Abeta vaccination. Precisely how Abeta vaccination chronically lowers Abeta levels and reduces Abeta-associated pathology remains unclear. Here, we provide an overview of these studies, with particular emphasis on our work with intranasal Abeta vaccination. Examples of other intranasal vaccines and mucosal adjuvants are presented. Taken together, these data have implications for the future development of an intranasal Abeta vaccine for humans. PMID- 11788049 TI - beta-Amyloid peptide vaccination results in marked changes in serum and brain Abeta levels in APPswe/PS1DeltaE9 mice, as detected by SELDI-TOF-based ProteinChip technology. AB - Although the pathogenesis of Alzheimer's disease (AD) is not fully understood, growing evidence indicates that the deposition of beta-amyloid (Abeta) and the local reactions of various cell types to this protein play major roles in the development of the disease. Immunization with the Abeta 1-42 peptide has been reported to decrease Abeta deposits in the brains of mutant amyloid precursor protein (APP/V717F) transgenic (tg) mice (Schenk et al. Immunization with amyloid beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173-177). We have replicated this finding in APPswe/PS1DeltaE9 tg mice, which also develop Abeta deposits in the brain. The immunized animals developed high titers of antibodies against Abeta 1-42 in serum, and Abeta deposits in the brains were significantly reduced. Using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry and ProteinChip((R)) technology, we detected trends toward increased soluble Abeta peptide in the brain and a decrease in assayable Abeta peptide in the serum of immunized compared with control animals. This last finding raises the possibility that anti-Abeta antibodies in the periphery sequester Abeta peptides or target them for degradation and in this way contribute to the enhanced Abeta clearance from the brain in immunized animals. PMID- 11788050 TI - Duration and specificity of humoral immune responses in mice vaccinated with the Alzheimer's disease-associated beta-amyloid 1-42 peptide. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), which is formed from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta in regions of the brain important for memory and cognition. Recently, vaccination of murine models of AD that exhibit Abeta deposition has halted or delayed the usual progression of the pathology of AD. Our group has demonstrated that vaccination of a doubly transgenic mouse model (expressing mutant APP and presenilin-1) with the Abeta 1-42 peptide protects these mice from the memory deficits they would ordinarily develop. This report further characterizes the Abeta 1-42 peptide vaccine in mice. Anti-Abeta response time course analysis indicated that at least three vaccinations (each 100 microg) were necessary to elicit a significant anti Abeta titer. Subsequent vaccinations resulted in half-maximal antibody titers of at least 10,000, and these titers were maintained for at least 5 months after the final boost. Peptide binding competition studies indicated that the highest humoral responses are generated against the N terminus of the Abeta peptide. Also, measurement of specific murine Ig isotypes in Abeta-vaccinated mice demonstrated a predominant IgG(1) and IgG(2b) response, suggesting a type 2 (Th2) T-helper cell immune response, which drives humoral immunity. Finally, lymphocyte proliferation assay experiments using Abeta peptides and splenocytes from vaccinated mice demonstrated that the vaccine specifically stimulates T-cell epitopes present within the Abeta peptide. PMID- 11788051 TI - Number of Abeta inoculations in APP+PS1 transgenic mice influences antibody titers, microglial activation, and congophilic plaque levels. AB - There have been several reports on the use of beta-amyloid (Abeta ) vaccination in different mouse models of Alzheimer's disease (AD) and its effects on pathology and cognitive function. In this report, the histopathologic findings in the APP+PS1 doubly transgenic mouse were compared after three, five, or nine Abeta inoculations. The number of inoculations influenced the effects of vaccination on Congo red levels, microglia activation, and anti-Abeta antibody titers. After three inoculations, the antibody titer of transgenic mice was substantially lower than that found in nontransgenic animals. However, after nine inoculations, the levels were considerably higher in both genotypes and no longer distinguishable statistically. The number of inoculations influenced CD45 expression, an indicator of microglial activation. There was an initial upregulation, which was significant after five inoculations, but by nine inoculations, the extent of microglial activation was equivalent to that in mice given control vaccinations. Along with this increased CD45 expression, there was a correlative reduction in staining by Congo red, which stains compact plaques. When data from the mice from all groups were combined, there was a significant correlation between activation of microglia and Congo red levels, suggesting that microglia play a role in the clearance of compact plaque. PMID- 11788052 TI - Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory. AB - Long-term vaccinations with human beta-amyloid peptide 1-42 (Abeta1-42) have recently been shown to prevent or markedly reduce Abeta deposition in the PDAPP transgenic model of Alzheimer's disease (AD). Using a similar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP+PS1 transgenic mice over an 8-month period, we previously reported modest reductions in brain Abeta deposition at 16 months. In these same mice, Abeta vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial protection from age related deficits in spatial working memory in the radial arm water maze task (RAWM) at 15.5 months. By contrast, control-vaccinated transgenic mice exhibited impaired performance throughout the entire RAWM test period at 15.5 months. The present study expands on our initial report by presenting additional behavioral results following long-term Abeta vaccination, as well as correlational analyses between cognitive performance and Abeta deposition in vaccinated animals. We report that 8 months of Abeta vaccinations did not reverse an early-onset balance beam impairment in transgenic mice. Additionally, in Y-maze testing at 16 months, all mice showed comparable spontaneous alternation irrespective of genotype or vaccination status. Strong correlations were nonetheless present between RAWM performance and extent of "compact" Abeta deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term Abeta vaccinations is task specific, with preservation of hippocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, Abeta vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments. PMID- 11788054 TI - From the Desk of the SBS Executive Director. PMID- 11788056 TI - High throughput cell-based assay of hematopoietic progenitor differentiation. AB - The in vitro efficacy of drug candidates relative to hematopoietic stem cell proliferation and differentiation is currently assayed through use of the clonogenic "colony assay." The extremely low throughput of this assay precludes its use in library screening and much drug discovery work. A rapid-throughput assay of progenitor cell differentiation based on the quantification of hematopoietic lineage-specific markers has been developed. The CELISA assay employs a single incubation with a lanthanide-conjugated primary antibody and subsequent time-resolved fluorescence spectroscopy. The rapid-throughput nature of this assay is enhanced by the use of cell culture-compatible filter plates to reduce the number of manipulations as compared to currently available cell-based assays. The culture and assay are done in 96-well plates, and the quantitation process requires approximately 1 hour. The myeloid, erythroid, and megakaryocytic lineages can be objectively quantified; data from the assay correlate extremely well with data generated through use of the traditional colony assay. This assay makes possible both rapid-throughput drug discovery and toxicity screening in the area of hematopoiesis. PMID- 11788057 TI - Development of SPC-ELISA: a new assay principle for the study of sulfated polysaccharide-protein interactions. AB - A sulfated polysaccharide-coating enzyme-linked immunosorbent assay (SPC-ELISA), a new screening assay for the study of interactions between sulfated polysaccharides and proteins, has been developed. Fibrinogen was used as representative for the protein. A microplate is coated with the sulfated polysaccharide to be tested and then incubated with various concentrations of fibrinogen. The bound fibrinogen is quantified by ELISA technique. The assay has been optimized with respect to coating procedure, incubation times, antibody concentrations, and detection conditions. Its capacity was demonstrated using three different sulfated polysaccharides: heparin, a sulfated glucuronogalactan extracted from a red algae, and a semisynthetic xanthan sulfate. Furthermore, the fibrinogen binding of semisynthetic laminarin sulfates with different degrees of sulfation showed good correlation with their anticoagulant effect as measured by fibrinogen clotting time. The intraassay as well as the interassay variations were lower than 8%. The binding properties observed in the SPC-ELISA correlated well with those found utilizing conventional gel permeation chromatography and fibrinogen affinity gel electrophoresis. Compared to these methods, the SPC-ELISA has several advantages: It is more rapid and far easier to perform, allows high throughput screening, and is suitable for automation. Furthermore, it is inexpensive, highly sensitive, and reproducible and has no special equipment requirements. Finally, the method represents the basis for multiple variations with regard to the target proteins as well as the detection methods. PMID- 11788058 TI - Application of beta-galactosidase enzyme complementation technology as a high throughput screening format for antagonists of the epidermal growth factor receptor. AB - We have applied enzyme complementation technology to develop a screen for antagonists of the epidermal growth factor (EGF) receptor. Chimeric proteins containing two weakly complementing deletion mutants of Escherichia coli beta galactosidase (beta-gal), each fused to the EGF receptor extracellular and transmembrane domains, have been stably expressed in C2C12 cells. In this cell line, formation of active beta-gal is dependent on agonist-stimulated dimerization of the EGF receptor. We have developed a homogenous 384-well assay protocol and have applied this to characterize the pharmacology of the receptor and to develop a high throughput screen (HTS) for EGF receptor antagonists. The assay is tolerant to DMSO concentrations of up to 2% and, across 21 passages in culture, exhibits an EC(50) for EGF of 5.4 +/- 3.6 ng/ml (n = 11) and a Z' of 0.55 +/- 0.13 (n = 11). A random set of 1,280 compounds was screened in duplicate at 11 microM to examine the robustness of enzyme complementation technology and to characterize the false-positive hit rate in the assay. Using a cutoff of 40% inhibition of EGF-promoted beta-gal activity, the hit rate on day 1 was 2.5% and on day 2 was 1.9%. After retesting the active compounds, the hit rate was reduced to 0.4%, of which one of the compounds was identified as a beta-gal inhibitor and the remainder appeared to be nonspecific inhibitors in the assay. This technology is amenable to automated screen workstations, there are highly sensitive chemiluminescent and fluorescent beta-gal assay reagents amenable to detection in miniaturized plate formats, and the assay benefits from a low false-positive hit rate. Enzyme complementation technology may have wide application within the HTS environment for the detection of modulators of receptor activation or inhibitors of protein-protein interactions in mammalian cells. PMID- 11788059 TI - High throughput fluorescence assays for the measurement of mitochondrial activity in intact human neuroblastoma cells. AB - The mitochondrial permeability transition event is implicated in the activation phase of apoptosis and necrosis, and is therefore postulated to play a role in many disease states. Mitochondrial permeability transition is therefore of increasing pharmaceutical interest. Drug discovery requires the rapid screening of compound libraries to identify functionally active ligands. We report the development of two fluorescence-based approaches for screening compound libraries for effects on mitochondrial function. These assays use the fluorometric imaging plate reader in 96-well format, and two commercially available dyes: JC-1 and calcein-AM. We show here that a JC-1 assay proved highly amenable to HTS implementation. By combining this with a calcein-based assay, these approaches gave complementary information: JC-1 facilitates the discovery of modulators of mitochondrial polarization from a library of approximately 100,000 compounds screened at 8 microM, and the calcein assay identifies permeability transition pore-specific inhibitors. PMID- 11788060 TI - High throughput studies of gene expression using green fluorescent protein oxidative stress promoter probe constructs: the potential for living chips. AB - Green fluorescent protein fusions were constructed with several oxidative stress promoters from Escherichia coli. These promoters were chosen for their induction by reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and hydroxyl radicals. When exposed to various free radical insults, the cells fluoresced with great specificity based on the corresponding ROS. In this work, we propose a way in which these constructs could be used to study the mode of action of a variety of antitumor drugs. This approach offers the possibility of complementing gene chip technology by the creation of living chips for high throughput screening as well as studying differential gene expression. PMID- 11788061 TI - High-density miniaturized thermal shift assays as a general strategy for drug discovery. AB - More general and universally applicable drug discovery assay technologies are needed in order to keep pace with the recent advances in combinatorial chemistry and genomics-based target generation. Ligand-induced conformational stabilization of proteins is a well-understood phenomenon in which substrates, inhibitors, cofactors, and even other proteins provide enhanced stability to proteins on binding. This phenomenon is based on the energetic coupling of the ligand-binding and protein-melting reactions. In an attempt to harness these biophysical properties for drug discovery, fully automated instrumentation was designed and implemented to perform miniaturized fluorescence-based thermal shift assays in a microplate format for the high throughput screening of compound libraries. Validation of this process and instrumentation was achieved by investigating ligand binding to more than 100 protein targets. The general applicability of the thermal shift screening strategy was found to be an important advantage because it circumvents the need to design and retool new assays with each new therapeutic target. Moreover, the miniaturized thermal shift assay methodology does not require any prior knowledge of a therapeutic target's function, making it ideally suited for the quantitative high throughput drug screening and evaluation of targets derived from genomics. PMID- 11788063 TI - Organ-specific complications in Venezuelan patients with AIDS. PMID- 11788064 TI - Spirituality and end-of-life care for an adolescent with AIDS. AB - AIDS is a life-threatening illness and, as is the case with all life-threatening illnesses, the spiritual beliefs of patients may influence their well being at the end of life. Patients' spiritual beliefs can offer comfort or be a source of distress. Health care professionals face ethical dilemmas, as they work with patients whose religious or spiritual idioms are incongruent with their own beliefs and traditions. The discussion in this case focuses on increasing health care professionals' sensitivity to the diverse spiritual needs of their patients. Guidelines are provided for assessment and interventions, as appropriate. PMID- 11788065 TI - Influenza and HIV: case report and review of potential interactions. AB - We describe a patient with AIDS who required hospitalization for influenza A. We review the classic pulmonary complications of influenza as seen in patients with HIV infection and discuss the clinical features, differential diagnosis, laboratory diagnosis, treatment, and prevention of influenza in this setting. PMID- 11788066 TI - Characteristics of HIV infection in patients fifty years or older in Michigan. AB - This study analyzed factors associated with human immunodeficiency virus (HIV) infection among persons ages 50 years or older at HIV diagnosis and examined differences in morbidity and survival between them and those ages 13 to 49 years. HIV-infected persons reported to the Michigan HIV/AIDS registry between January 1990 and October 2000 were analyzed. Of 12,614 HIV-infected persons selected, 938 (7.4%) were ages 50 years or older at HIV diagnosis. Persons ages 50 years or older at HIV diagnosis were twice as likely to be male (odds ratio [OR]: 1.9) than female. They were slightly at higher risk of contracting HIV through blood products (OR: 1.53) or heterosexual contact (OR: 1.24) than through injection drug use, but the difference was not statistically significant. They were twice as likely to report unknown HIV risk (OR: 1.8) than injection drug use and were significantly less likely to be men who have sex with men (OR: 0.64) than injection drug users. The prevalence of selected acquired immune deficiency syndrome (AIDS)-defining conditions was similar between the two age groups. However, HIV dementia was more commonly diagnosed among older persons, whereas disseminated Mycobacterium avium was less commonly diagnosed in this age group. The overall mean survival was significantly shorter among persons ages 50 years or older (73.5 months [standard deviation (SD)]: 2.21 compared with their counterparts [112.3 months (SD: 0.77)], even after adjusting for CD4 count at HIV diagnosis. Older persons appeared to have contracted HIV through heterosexual contact, blood products, or injection drug use and to have a short survival. This age group should no longer be overlooked. PMID- 11788067 TI - School-age children with perinatally acquired HIV infection: medical and psychosocial issues in a Philadelphia cohort. AB - With the advent of highly active antiretroviral therapy (HAART), children with perinatally acquired human immunodeficiency virus (HIV) are living into their school-age years and adolescence. This study was designed to explore some of the medical, educational, and psychosocial aspects of these older children's lives. A retrospective chart review of 85 HIV-infected, school-age patients was conducted to obtain demographic and clinical data. Fifty-four of these patients and their caregivers were interviewed regarding school-related issues. Although 50% of the children had experienced severe symptoms (Centers for Disease Control [CDC] class C) related to their HIV infection, their mean CD4 count at the time of the study was 722 cells per microliter, and 40% had an undetectable (<40 copies per milliliter) viral load. More than two thirds of the patients were not hospitalized over the course of the year. The mean developmental quotient (DQ) for the group was 85; 12% of the children had a DQ below 70. Nearly all (85%) of the children were attending public school, and 76.5% were in the appropriate grade level for their age. More than half (53%) required some special services while in school. Forty-three percent of the children had been told their HIV status, and the average age at disclosure was 9 years. School employees had been told the child's diagnosis in 23% of the cases. As the perinatally acquired HIV infected population ages, health care providers must be cognizant of the range of issues, both medical and social, confronting these children. PMID- 11788068 TI - Risk factors for syphilis among incarcerated women in Rhode Island. AB - Syphilis remains a significant problem in the United States. The prison environment is an ideal location to identify and treat syphilis. We undertook this study to describe the correlates and risk factors for syphilis among incarcerated women in Rhode Island. The study design was a review of all cases of syphilis identified through routine screening in the state prison and a case control study. Between 1992 and 1998, among 6,249 incarcerated women, 86 were found to have syphilis; of these, 29 were primary and secondary cases representing 49% of infectious cases of syphilis in women in the state. The prison environment offers a unique opportunity for the diagnosis and treatment of syphilis. PMID- 11788069 TI - Impact of adherence to antiretroviral therapy in HIV-1-infected patients at a university public service in Brazil. AB - The objective of this study was to assess if a simple evaluation, adherence to antiretroviral therapy, would correlate to clinical and laboratory outcomes. We followed an open cohort of patients from a public teaching hospital AIDS outpatient clinic. Patients were categorized according to adherence as: regular (Reg), optimal, all doses all days, tolerating only irregular timing (+/- 2 hours) of intake; quasi-regular (qReg), those missing up to four doses or 1 full day during a month; irregular (Irreg), all other irregular regimens, and ignored (Ign), those without information. The results from a simple questionnaire were compared to CD4+ cell counts and human immunodeficiency virus type 1 (HIV-1) RNA plasma viremia. One hundred eighty-two HIV-1-infected patients (126 males, 69%; 56 females, 31%) were analyzed. Information on adherence was available for 168 (90%). Reg adherence was reported by 75 (41%) patients, qReg adherence by 35 (19%), and Irreg by 53 (29%) of patients. The main reasons for nonadherence were forgetfulness, intolerance, use of alcohol, and misunderstanding of prescription. A significant increase of CD4+ T-cell counts and absolute gain were only observed among Reg and qReg users (p < 0.001). The median viral RNA load log10 decreases were -1.68, -1.45, -0.9 log, respectively, for Reg, qReg, and Irreg patients (p = 0.043, Kruskal-Wallis). Development of and death from AIDS occurred almost exclusively among those with Ign or Irreg adherence. Previous use of antiretroviral therapy may have had an impact in treatment response. Individuals who were treatment-naive were more likely to be Reg users (41%). Although more refined methods to assess adherence should be implemented when available, the inability to do so should not prevent simple, albeit subjective measurements that also correlate with favorable outcome. Mechanisms to improve adherence should be considered an integral part of antiretroviral therapy. PMID- 11788070 TI - Perinatal guidelines available. PMID- 11788071 TI - Combination reduces HCV load. PMID- 11788072 TI - Coinfection with hepatitis viruses and HIV: good and bad news. PMID- 11788073 TI - Successful treatment of AIDS-related disseminated cutaneous sporotrichosis with itraconazole. AB - Sporotrichosis is a chronic granulomatous mycosis caused by a dimorphic fungus, Sporothrix schenckii. The most common manifestations of infection are lymphocutaneous and fixed-cutaneous types. In the case of immunosuppressed patients, and particularly in patients with acquired immune deficiency syndrome (AIDS), it occurs as disseminated cutaneous disease. This is a report of a 28 year-old male patient who presented with disseminated cutaneous and hematogenous sporotrichosis involving multiple ulcerative, nodular lesions in various body areas. Treatment consisted of 300 mg/d of itraconazole, which resulted in clinical and mycological cure. PMID- 11788074 TI - Chlamydia trachomatis and Mycobacterium tuberculosis lung infection in an HIV positive homosexual man. AB - A 31-year-old homosexual man, who was human immunodeficiency virus (HIV)-positive was admitted for fever and cough. Chest computed tomography (CT) revealed the presence of diffuse interstitial reticular nodulation, and brain nuclear magnetic resonance imaging showed the presence of nodular frontal lesions. Microscopic examination of sputum and other body fluids showed the presence of acid-fast bacilli and culture-only growth Mycobacterium tuberculosis. Serology for respiratory tract pathogens was negative except for Chlamydia. An antibody titer in the immunoglobulin G (IgG) class of 1:64 for Chlamydia pneumoniae and, unexpectedly, an antibody titer of 1:1024 for C. trachomatis were found. The patient was successfully treated with antituberculosis agents, and clarithromycin, for presumptive chlamydial infection. PMID- 11788075 TI - Emerging role of riboflavin in the treatment of nucleoside analogue-induced type B lactic acidosis. AB - Type B lactic acidosis is a rare and often fatal complication seen in patients receiving the nucleotide analogues zidovudine, stavudine, didanosine, and lamivudine. We describe a case of a 51-year-old human immunodeficiency virus (HIV)-positive woman receiving three nucleotide analogues. She presented with nausea, vomiting, abdominal pain, and hepatic steatosis. Signs of mitochondrial toxicity were demonstrated by diffuse myopathy and pancreatitis. Serum riboflavin levels documented a deficiency that was treated with 50 mg of riboflavin daily. Immediately after treatment, serum blood urea nitrogen level, lactic acid levels, and arterial blood pH all returned to normal values. Her signs of mitochondrial toxicity also improved after treatment with riboflavin. Successful reversal of the patient's type B lactic acidosis after riboflavin therapy suggested that riboflavin deficiency plays a direct role in the development of nucleotide analogue-induced lactic acidosis. It is impossible to predict which patients are predisposed to the development of this syndrome. For this reason, it may be important to screen and treat riboflavin deficiency in patients on nucleoside analogues. PMID- 11788076 TI - Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection. AB - Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes. PMID- 11788077 TI - Changing patterns of "hospital-at-home" care use by persons with AIDS in the era of combination antiretroviral therapy. AB - This study describes how hospital-at-home care (HHC) use by persons with acquired immune deficiency syndrome (PWA) has changed since the introduction of combination antiretroviral therapy (ART). For this study, all adult PWA (877) admitted for the first time to the HHC program, established for PWAs in the metropolitan area of Rome, between January 1994 and December 1998, were enrolled. Temporal changes in sociodemographic and clinical characteristics were evaluated. For subjects who concluded their first HHC cycle (851/877), the reasons for ending the service were assessed over time. From 1994 to 1998, the proportion of patients admitted to HHC of those living with AIDS in the Rome area decreased significantly (from 15.1% to 7.5%), while the median CD4+ cell count at HHC entry increased significantly. The proportion of patients referred to outpatient services at the end of their cycle of HHC increased sevenfold from 1994 to 1998, with a steep increase between 1996 and 1997. In multivariate analysis, only the use of triple-combination ART was significantly associated with referral to outpatient care (odds ratio [OR] = 4.26; 95%, confidence interval [CI] = 1.94 9.34). The results suggest that HHC use by PWAs in the ART era has diminished, while the HHC use pattern has also changed: there is a growing tendency to provide care to patients with less advanced human immunodeficiency virus (HIV) disease, prior to the beneficial effects of drugs, and the consequent referral to outpatient care. PMID- 11788078 TI - A package of care for HIV in the occupational setting in Africa: results of a pilot intervention. AB - We describe a package of care including prevention, education, and therapeutics for human immunodeficiency virus (HIV) infection in the occupational setting in sub-Saharan Africa and evaluate the outcomes of this package over 1 year. A prospective cohort study was done between 1999 and 2000 in a sugar mill employing 386 men in Kwa-Zulu Natal in South Africa. A package of care for HIV in the occupational setting was developed and implemented in 1999. This response included prevention, education, and therapeutic components. Outcomes measured included condoms distributed, sexually transmitted infections treated, numbers of HIV-infected individuals entering into the therapeutic pathway developed, and numbers of individuals counselled and tested for HIV. HIV prevalence in this population was 27.15% in January 1999. Between 1999-2000 in this workforce of 386, 58 of 102 (54%) individuals with HIV were identified through voluntary counselling and testing. Of these, 48 (82.8%) voluntarily entered the HIV treatment pathway. Condom distribution in the sugar mill increased 400% and the number of sexually transmitted infections treated at the mill decreased by 88% during this time period. Using AVERT software to model HIV infection over time a decrease in incidence of 91.67% from that expected in this population was calculated. 11 HIV infections were averted in a single year of this program. HIV/acquired immune deficiency syndrome (AIDS) is prevalent in the occupational setting in South Africa. This setting can provide a venue for HIV care and prevention. A package of care for HIV including prevention, education, and therapeutics can be effective in both providing care for HIV-infected individuals and preventing new infections. PMID- 11788079 TI - Genotyping kit approved. PMID- 11788080 TI - Religious beliefs affect teen sexual behavior. PMID- 11788082 TI - Newborn screening, informed consent, and future use of archived tissue samples. AB - Recent advances in genetic technologies have combined with established protocols for genetic screening to provide immense benefits to individuals and the public. In most American jurisdictions, newborn screening is mandated by law and does not require parental consent for the collection or testing of the blood samples. Screening programs have been successful in identifying affected infants at an early stage for effective treatment of some genetic diseases. The public health benefit of screening programs is recognized and affirmed. However, collections of surplus, stored samples have become immensely attractive to researchers in medical genetics and the biomedical sciences. As geneticists have sought access to the newborn screening samples, they have recognized concerns related to whether they should use the samples, and, if so, under what conditions. This paper addresses the ethical issues associated with genetic screening and recommends an informed consent protocol that may be used to balance individual and parental rights with the interests of researchers who wish to use surplus samples in studies of genetic disease. PMID- 11788083 TI - Psychological aspects of genetic counseling. XIV. Nondirectiveness and counseling skills. AB - The difficulties some professionals have in achieving nondirective goals is largely due to the inadequate and ineffective application of basic counseling skills. The "new genetics," with its emphasis on decision-making in association with genetic testing, is among the most demanding forms of personal counseling, the effectiveness of which depends largely on the professional's human experience and counseling abilities. Examples are given showing inadequacies in professional responses to clients in genetic counseling which, in turn, defeat the achievement of a nondirectiveness that is helpful to clients, supports their self directedness, and leaves them more psychologically prepared for quality decision making. Other models of counseling (e.g., shared decision making) will not fare any better than the nondirective one unless counseling skills of professionals in genetic services are upgraded in a significant way. Professional organizations need to give greater attention to the training and postgraduate supervision of all personnel involved in genetics services. PMID- 11788084 TI - Genetic counseling issues in Latinos. AB - Close to 12% (33 million) of the U.S. population is of Latino ethnocultural background, and it is estimated by the year 2005 they will become the largest ethnic minority. This article describes the demographic, social, economic, and cultural characteristics of the Latino population in the United States. Main health problems of Latinos and barriers to access to equitable health care are described. Health beliefs of relevance in the provision of health care in general, and of genetic counseling in particular, are reviewed. Some key nuances of genetic counseling to Latinos are discussed, such as the problems of language and other pitfalls in communication, the role of nondirectiveness in Latino culture, the medicalization of pregnancy, the language of prospective risks, and the meaning of disability. To provide culturally appropriate genetic counseling to Latinos, genetic professionals must be conversant with their personal and social history, culture, and traditions. At the same time, cultural stereotyping must be avoided, as the individuality of each patient must be recognized, acknowledged and respected. PMID- 11788085 TI - Application of population screening principles to genetic screening for adult onset conditions. AB - Recent advances in molecular genetics have highlighted the potential use of genetic testing to screen for adult-onset chronic diseases. Several issues must be addressed, however, before such tests can be recommended for population-based prevention programs. These issues include the adequacy of the scientific evidence, the balance of risks and benefits, the need for counseling and informed consent, and the costs and resources required. Ongoing assessment of the screening program and quality assurance of laboratory testing are also needed. This paper considers the application of general principles for mass screening to genetic testing for susceptibility to adult-onset chronic diseases. Evaluation of proposals for genetic screening in context of these principles reveals that needed evidence is often absent, particularly with respect to the predictive value of tests, efficacy of interventions, and social consequences of testing. The principles of population screening are developed into a framework for public health policy on genetic screening that has three stages: assessment of the screening test and interventions for those who test positive, including assessment of risks and costs, policy development, and program evaluation. Essential elements are identified, including evaluation of evidence and processes for consensus development and program evaluation. The proposed framework for public health policymaking outlined in this commentary, when combined with future efforts that involve an authoritative consensus process, may be useful for the evaluation and planning of genetic screening programs aimed at reducing morbidity and mortality from adult-onset chronic diseases. PMID- 11788086 TI - Anonymous predictive testing for Huntington's disease in the United States. AB - The widespread use of a predictive genetic test for Huntington's disease (HD) since 1993 has brought to the forefront issues regarding genetic privacy. Although the possibility of anonymous genetic testing has been discussed, its use in the United States has not been described previously. We review the experiences of 11 genetics specialists with anonymous predictive testing for HD. We found that more men than women requested anonymous testing, for reasons that more often related to personal privacy than to insurance or discrimination concerns. A number of approaches to anonymity were used, and genetics specialists varied in the degree to which they were comfortable with the process. A number of legal, medical, and practical questions are raised, which will require resolution if anonymous testing is to be performed with a greater frequency in the future. PMID- 11788087 TI - Points to consider in designing a clinical trial to ascertain the utility of a genetic screening test. AB - In designing a clinical trial to ascertain the utility of a genetic screening test, the follow recommendations should be considered: (1) imbed the genetic test in a genetic service; (2) choose a specific outcome to monitor; (3) compare two strategies for achieving the desired outcome; (4) assemble a multidisciplinary team; (5) attempt to reach all potential subjects in a defined region; (6) derive an outcome for each subject; (7) assess each expected benefit and burden. PMID- 11788088 TI - Cystic fibrosis carrier screening: steps in the development of a mutation panel. AB - The American College of Obstetricians and Gynecologists (ACOG) has now officially recommended that cystic fibrosis (CF) carrier screening be offered to all Caucasian pregnant couples. The American College of Medical Genetics (ACMG) has officially recommended that CF-carrier screening be performed using a 25-mutation panel. Data is presented to indicate that an expanded pan-ethnic mutation panel, containing at least 47 mutations, would provide significantly greater CF-carrier identification in the ethnically diverse U.S. population. PMID- 11788089 TI - Cystic fibrosis mutation testing in Italy. AB - In Italy, Cystic fibrosis (CF) mutation frequency differences have been observed in different regions. In the northeastern Veneto and Trentino Alto Adige regions, a complete cystic fibrosis transmembrane conductance regulator (CFTR) gene screening in CF patients detected through a newborn screening program has identified about 90% of the mutations. In these two regions, the current detection rate using a CF screening panel containing the 16 most common mutations is 86.6%. CF mutations in some other Italian regions have not been so thoroughly analysed. Available data indicate that a more general national screening panel comprising 31 mutations may detect about 75% of all CF mutations in Italy. PMID- 11788090 TI - Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations. AB - Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (DeltaF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G --> T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant DeltaF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity. PMID- 11788091 TI - Involvement of CFTR gene alterations in obstructive and nonobstructive infertility in men. AB - There have not been many studies concerning CFTR gene alterations in nonobstructive causes of male infertility and subfertility, and in those that have been published, the results reported are not concordant. Therefore, we proposed to determine, in a representative unselected sample of men who were sent for microsurgical epididymal sperm aspiration, if different types of male infertility and impaired fertility were associated with CFTR gene alterations. We screened 80 men with idiopathic azoospermia, 50 men with severe oligozoospermia, 70 men with oligoasthenoteratozoospermia, and 7 men with congenital bilateral absence of the vas deferens (CBAVD), as well as 95 controls from Slovenia, for mutations in 10 CFTR exons that include the majority of the most common cystic fibrosis (CF) disease causing mutations. We also wanted to evaluate the risk for CF in children born after the intracytoplasmic sperm injection (ICSI) method of in vitro fertilization (IVF). No tested individual had mutations in both CFTR alleles. Altogether 13 different nucleotide alterations were identified. The frequencies of both CFTR gene alterations and polymorphisms did not differ significantly between the control group and men with idiopathic nonobstructive azoospermia and subfertility, but were significantly increased in men with CBAVD (DeltaF508, p = 0.039; IVS8-5T, p = 0.006). Our results suggest that CFTR mutations are not associated with errors in spermatogenesis and nonobstructive pathology of urogenital tract in men with any frequency. However, genetic counseling and CFTR mutation screening continue to be recommended for men with obstructive azoospermic conditions and their female partners. PMID- 11788092 TI - A pilot survey of cystic fibrosis clinical manifestations in CFTR mutation heterozygotes. AB - A cystic fibrosis (CF) heterozygote incidence higher than in the general population has been repeatedly reported in conditions which include clinical features found in CF, like pancreatitis, disseminated bronchiectasis, and allergic bronchopulmonary aspergillosis. Some cases may be explained by an unidentified compound heterozygosity; others could be manifesting heterozygotes. This study was aimed at detecting the incidence of CF-related clinical features in a population of carriers. A group of 261 obligate heterozygotes (mean age, 44 years) and a control group, composed of 201 individuals negative for a standard mutation panel (mean age, 36 years), were surveyed for possibly CF-related conditions (asthma, bronchiectasis, pneumothorax, allergic bronchopulmonary aspergillosis, sinusitis, nasal polyps, gallstones, liver cirrhosis, diabetes, pancreatitis, bone fractures, plus hypertension). A questionnaire was administered, and the accuracy of the statements was evaluated by phone interviews. There was no difference between heterozygotes and controls, with the exception of hypertension (carriers 28/261, controls 7/201, p = 0.004), and, in males, nasal polyps (carriers 7/126, controls 0/102, p value = 0.0178), and, again, hypertension (carriers 17/126, controls 5/102, p value = 0.0407). To avoid age bias, 126 heterozygotes matched to controls of the same gender and age were separately processed: these two groups showed no significant differences. CF related clinical manifestations in obligate CFTR mutation heterozygotes are not more represented than in individuals with a low risk of being carriers. PMID- 11788093 TI - Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay. AB - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS; MIM SACS 270550) is frequent in northeastern Quebec. Two causal mutations have been identified in the 11.7-kb single exon sacsin gene by sequence-based analyses. Mutation g.6594delT (DeltaT) was reported in 96% of the patients whereas a g.5254C --> T nonsense mutation has been observed only in 2 families. Here we report a reliable and inexpensive method to detect more than 95% of the ARSACS disease alleles from northeastern Quebec using allele-specific oligonucleotide (ASO) hybridization. This procedure is being incorporated into the diagnosis of ARSACS, as well as being used for carrier detection in at-risk families from northeastern Quebec. PMID- 11788094 TI - Gene dosage analysis in Silver-Russell syndrome: use of quantitative competitive PCR and dual-color FISH to estimate the frequency of duplications in 7p11.2-p13. AB - Silver-Russell syndrome (SRS) describes a heterogeneous malformation syndrome mainly characterized by intrauterine and postnatal growth retardation (IUGR/PNGR). Approximately 10% of SRS cases have been associated with maternal uniparental disomy (matUPD) 7. This suggests the involvement of at least one imprinted gene on chromosome 7 in the pathogenesis of SRS. Additionally, two familial and one single SRS patients have been published with an interstitial duplication in 7p11.2-p13, including the genes GRB10 and IGFBP1; IGFBP3 was investigated in only one case revealing duplication; conversely, double gene dosage of EGFR was excluded in all 3 patients. Two further cytogenetically abnormal cases, one with a paracentric inversion (7)(p14p12) and one with matUPD7/partial trisomy for 7p13-q11, confirmed that the proximal short arm of chromosome represents an interesting region possibly harboring (a) candidate gene(s) for SRS. Although previously published investigations on the genes GRB10, IGFBP1, IGFBP3, and EGFR report neither disease-relevant mutations nor abnormal imprinting patterns, the SRS cases with chromosomal duplications suggest that variation of gene copy number might be a further type of mutation. To obtain meaningful results on the frequency of duplications in proximal 7p, we screened 32 SRS patients using quantitative PCR assays for GRB10, IGFBP1, IGFBP3, and EGFR. The data were confirmed by dual-color fluorescence in situ hybridization (FISH) of spot check samples. Results obtained by both methods exclude duplications in all analyzed patients and indicate an overall percentage of duplication among SRS patients between 2.4% (GRB10) and 5% (IGFBP1). By testing and evaluating quantitative competitive PCR for various loci, we developed a practical approach for gene dosage analysis which can be easily established for routine purposes. PMID- 11788095 TI - Allelic loss analysis by capillary electrophoresis: an accurate, automated method for detection of deletions in solid tumors. AB - In this report, we describe a fast and accurate capillary electrophoresis, PCR based method for detecting loss of allelic heterozygosity in solid tumor samples. This automated method requires small sample sizes, and data can be obtained in less than 15 min. The method is particularly powerful for uncovering deletions in tumor sample preparations containing significant normal tissue contamination. PMID- 11788096 TI - Prevalence of CTLA-4 polymorphism A49G in Ashkenazi Jews. AB - Type 1 diabetes has been associated with numerous genetic loci. One locus, IDD12, includes the gene for cytotoxic T lymphocyte antigen (CTLA-4). A polymorphism at position 49 in the CTLA-4 gene, causing a substitution of Thr --> Ala, has been associated with various autoimmune diseases, including diabetes. The frequency of the polymorphism in European and Oriental populations has been recorded, but the frequency among different ethnic groups within the United States has yet to be established. In the present study, we analyzed 100 DNA samples from Ashkenazi Jews to determine the polymorphism's prevalence in that population. The A/A genotype was found in 49% of individuals, 41% were heterozygous A/G, and 10% possessed the G/G genotype. The prevalence of the A/A genotype in Ashkenazi Jewish population is the highest reported to date. The incidence of the homozygous G/G genotype within Spanish controls, 8.8%, is the lowest, followed by the Ashkenazi general population. The frequency of the non-diabetes-associated A/A genotype shows a similarity to the frequency of the diabetes-susceptible HLA haplotype, DR4-DQ8. The low prevalence of the autoimmune-associated G allele among Ashkenazi Jewish and Spanish populations may explain a lower than expected incidence of diabetes in HLA-susceptible populations. PMID- 11788098 TI - Hair removal with a combined light/heat based photo-epilation system. AB - BACKGROUND: A variety of lasers and light sources have been used for removal of unwanted hair. A novel, new, flashlamp-based device, with a mechanism of action based on a combination of both emitted light and heat, has been developed for safe and reliable hair removal. OBJECTIVE: To assess the efficacy and safety of hair removal by a combined light/heat based photoepilation system. METHODS: A pilot trial was undertaken. Twenty one anatomic sites received one to three treatments with the SpaTouch light/heat based photoepilation system. Fluences ranging from 6.25 to 6.45 J/cm(2) and pulse duration of 35 ms were used. Evaluations of hair regrowth was performed at 4 months after the last treatment by comparing the terminal hair count to the baseline values. Patient satisfaction and potential complications were evaluated. RESULTS: Average hair reduction after photoepilation was 27% for one to three treatments at 4 months following the final treatment. 46% and 15% of subjects reported being 'mildly pleased' and 'very pleased' with the results of treatment. No hyperpigmentation, hypopigmentation or scarring was observed at 4 months after treatment. CONCLUSION: The SpaTouch light/heat based photoepilation system represents the newest efficient and safe method in hair removal. Further study of optimal parameters is required. PMID- 11788099 TI - Long-term hypopigmentation induced by diode laser photo-epilation. PMID- 11788100 TI - IMCAS - International Master Course on Ageing Skin. Paris, January 2001. Proceedings. PMID- 11788102 TI - Observations from the CDC. Community Prevention Study: contributions to women's health and prevention research. PMID- 11788103 TI - Toward optimal health: the experts discuss oral contraception. PMID- 11788104 TI - Setting a local research agenda for women's health: The National Centers of Excellence in Women's Health. AB - Although women's health research expanded greatly in the past 10 years, significant gaps in knowledge remain. Prioritization and promotion of research will help assure continuing progress in closing such gaps and improving the health of women. Although a comprehensive agenda for the new millennium has been developed at the national level, the process for establishing a local research agenda is not well defined. The purpose of this study was to describe criteria for and barriers to establishing a local research agenda in women's health. A secondary aim was to describe mechanisms for identifying women's health researchers and for facilitating multidisciplinary research. Directors of Research at National Centers of Excellence in Women's Health (CoEs) (n = 18) were surveyed by mail for this information. The results indicate that the local research agenda should emphasize health issues that are prevalent in women, research that is likely to establish treatment, psychosocial/cultural factors, and quality of life issues. The process of setting a research agenda should include input from the communities served as well as from scientists. Critical evaluation of scientific strengths and weaknesses is an essential preliminary step in prioritizing research opportunities in order to implement and evaluate a research agenda in women's health. PMID- 11788105 TI - Identifying and caring for underserved populations: experience of the National Centers of Excellence in Women's Health. AB - From 1996 through 1998, 18 National Centers of Excellence in Women's Health (CoEs) were designated by the Office on Women's Health (OWH) of the U.S. Department of Health and Human Services (DHHS). These CoEs were charged with developing standards for comprehensive, multidisciplinary, and culturally competent approaches to women's health. One specific mandate to the CoEs was to address the needs of underserved women. This paper presents the efforts of the CoE Racial and Ethnic Minority and Underserved Women Working Group to describe the work done within the CoEs to meet this mandate. One method of defining underserved populations is the seven-point definition used in the current "Index for Primary Care Shortage," which categorizes underserved populations based on characteristics including race, ethnicity, geography, and health outcomes. The definition allows the local identification of underserved communities based on this group of variables. The analysis included in this paper focuses specifically on the CoEs' efforts to operationalize this definition in order to meet the clinical care needs of women who are of low socioeconomic status (SES), racial or ethnic minorities, or non-English speaking. A brief review of the literature linking these characteristics to being underserved is provided, followed by examples of ongoing activities at the 15 currently funded CoEs, to understand the needs of diverse women, to improve the quality of care provided to women, and to address healthcare needs of underserved women who meet this definition. Efforts to serve three additional underserved populations defined by age, sexual orientation, and disability status are also presented. PMID- 11788106 TI - Training programs for healthcare professionals in domestic violence. AB - Although women who experience domestic violence seek healthcare services frequently, screening and counseling rates remain low, and healthcare professionals report feeling inadequately trained to care for abused women. The English language literature from 1989 to 1999 was searched to identify and evaluate published assessments of the education of healthcare providers in domestic violence toward women. Major deficiencies in program evaluation were found. They included the use of a historical comparison group, lack of an experimental design, selection of nonstandardized outcomes without clinical performance measures, short-term follow-up, limited documentation of course content and theory, and lack of focus on the impact of programs on abused women. Educational programs generally consisted of a single session of limited duration (1-3 hours). Based on published reports, it appears that few rigorously designed evaluations have been conducted of training programs for healthcare providers in the detection and treatment of women affected by domestic violence. PMID- 11788107 TI - Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women. AB - The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first coronary heart disease (CHD) primary prevention trial of the cholesterol-reducing agents called "statins" to include women. For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease (CVD) who had average low-density lipoprotein cholesterol (LDL-C) and below average high-density lipoprotein cholesterol (HDL-C), 20-40 mg/day lovastatin reduced first acute major coronary events (AMCEs) 37% (for those receiving placebo and lovastatin, respectively, 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infarction [MI], unstable angina, or sudden cardiac death; relative risk [RR] 0.63; 95% confidence interval [95% CI] 0.50, 0.79; p < 0.001). Statistically significant reductions in prespecified secondary end points (coronary revascularizations, unstable angina, MI, cardiovascular end point events, and coronary end point events) were also associated with lovastatin treatment in the overall cohort. This paper provides results in women, a prespecified subgroup. Among women, 20-40 mg/day lovastatin reduced LDL-C 25% and increased HDLC 9% (p < 0.001). A prespecified analysis revealed consistency with the overall results regardless of gender (i.e., there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin). However, the number of women who had an AMCE was small, and there was insufficient power to detect a treatment group difference among women (7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo, respectively; RR 0.54; 95% CI 0.22, 1.35; p = 0.183). Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin, but again, the numbers of events were small and the differences were not statistically significant. Chronic long-term treatment with lovastatin was well tolerated, with no treatment group differences in the frequency of cancer, muscle symptoms, and clinically important liver enzyme elevations. In AFCAPS/TexCAPS, a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD. However, because of the small number of events, there was insufficient power to detect significant treatment group differences. Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C, and chronic long-term treatment with 20-40 mg/day lovastatin was well tolerated in women. PMID- 11788108 TI - Possible beneficial effect of exercise, by reducing oxidative stress, on the incidence of preeclampsia. AB - We hypothesize that regular exercise enhances antioxidative enzymes in pregnant women, which reduce oxidative stress and, thus, the incidence of preeclampsia. Oxidative stress with enhanced lipid peroxide formation could lead to endothelial dysfunction in preeclampsia. Other conditions, such as increased transferrin saturation and decreased iron-binding capacity, directly and indirectly promote the process of oxidative stress and subsequent endothelial dysfunction. Exercise increases oxidative metabolism and produces a prooxidant environment. This acidic environment during exercise (at or beyond anaerobic threshold) promotes oxygen release from hemoglobin and increases in PO(2) in tissues, as well as releases iron from transferrin. When exercise is repeated regularly, the body promptly adjusts so that oxidative stress is eliminated or reduced. The body's adaptations to a regular exercise habit seem to have an antioxidant effect. In humans, training effects have been identified with an enhanced activity of antioxidative enzymes. Another concerted adaptation that regular exercise brings to women's bodies is resistance against production of prooxidants by increasing the number of mitochondria. Equally important is a training effect that decreases susceptibility to lipid peroxidation. Evidence suggests that physically active women are less likely to develop preeclampsia. In theory, intracellular and extracellular conditions resulting from regular exercise should counteract the enhancement of oxidative stress, thus interfering with the process leading to endothelial dysfunction. This position paper describes a hypothesis and includes a brief review of exercise physiology and biochemical research in preeclampsia. Unlike other preventive treatments, such as aspirin or calcium supplements, a regular exercise habit leads to a positive and healthy lifestyle without concern of side effects. PMID- 11788109 TI - Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. AB - The objective of this study was to evaluate the psychological side effects of a transvaginal natural progesterone gel in hormone replacement therapy (HRT). This 3-month preliminary study was part of a multicenter study previously performed in our center. We enrolled 49 women (ages 18-45 years) with hypothalamic amenorrhea (HA) (n = 40) and premature ovarian failure (POF) (n = 9). Estrogenized patients applied vaginal progesterone gel (4% or 8%) every other day for six doses per month. The Hopkins Symptom Checklist (HSCL), a psychometric profile test, was administered at baseline, day 13 of cycle 2, day 24 of cycle 2, and day 24 of cycle 3. Application of the progesterone gel caused no significant change in HSCL total scores or individual symptom scores for somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety. Natural vaginal progesterone gel can be an effective alternative to oral progesterone for women on HRT. PMID- 11788111 TI - Women's Health LiteratureWatch. PMID- 11788110 TI - An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy. AB - Treatment of major depression in menopausal women is controversial. Estrogen replacement therapy (ERT) treats mild depression but may not treat more severe depression in this population. Antidepressants are recommended as treatment for major depression in menopausal women, but the specific efficacy of antidepressants has not been examined in menopause-associated depression. Twenty two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 score < or =7 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p < 0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers. Subjects responded well to mirtazapine regardless of whether their depression preceded ERT use or developed after ERT was initiated. Therapeutic response also appeared independent of menopausal status (perimenopausal vs. postmenopausal), ERT preparation, and concomitant use of medroxyprogesterone. Mirtazapine is an effective treatment for major depression in perimenopausal and postmenopausal women whose depression precedes ERT use and does not respond to ERT or whose depression develops after ERT is initiated. PMID- 11788112 TI - [Functional assessment scales and lower limb amputation]. AB - INTRODUCTION: This paper is a review of the literature on assessment tools in lower limb amputees. MATERIAL AND METHODS: The authors have research on Medline(R) data base the different tools with keys words "lower limb amputee or amputation, functional evaluation or outcome assessment tools, activity of daily living", and have completed the research with the references of papers. RESULTS: A comprehensive approach of the consequences of an amputation and of the outcome of prosthetic care should include an evaluation of gait, use of the prosthesis in activities of daily life, acceptability and satisfaction with the device. DISCUSSION: Functional assessment tools that are validated are recent, and most of them were developed in English. They take into account the use and the acceptance of the device, but there is no study using them for an important sample population. CONCLUSION: It is now necessary to translate the recent tools into French, and to confirm their validity and sensitivity to change. PMID- 11788113 TI - [Suprapubic reflex. Electrophysiological study in normal patients]. AB - INTRODUCTION: In spinal cord injuries patients, tapping the suprapubic aera is a strong stimulus to ellicit detrusor contraction and can be used in the management of neurogenic bladder. This stimulation also determines a perineal muscles contraction. This striated response was mentionned in animal studies but never specifically analysed in men especially in normal subjects. AIMS OF THE STUDY: Our objective was to describe pelvic floor responses with measurement of reflex latency following suprapubic mechanical stimulation. METHODS: 21 patients without neurological disease were studied. They were 14 women and 7 men. Mean age was 51 (SD=14,2). Motor responses were recorded with a needle electrode inserted in the left bulbocavernosus muscle. Stimulation was delivered with an electromechanical hammer, tapping directly on the suprapubic aera. RESULTS: A polyphasic muscular response was always and easily elicited in all patients. Mean latency was 67,5 ms. (SD = 14,7). The reproducibility between the first and second mechanical responses was good with no statistical difference (r=0,966; p=0,0001). DISCUSSION: Our study clearly demonstrates a suprapubic bulbocavernosus reflex (SBR). Many arguments can be retained for a polysynaptic reflex (polyphasic response, habituation and short latency of the reflex, mean latency in the habitual values of R2 responses following electrical stimulation of the dorsal nerve of the penis). We hypothetize that: the true stimulus is the stimulation of the bladder wall tenso-receptors; integration level of the SBR is the sacral segments and the efferent limb the pudendal nerve; afferent pathways could be vehicled by pelvic nerve fibers. CONCLUSION: Competition between a preponderant (or exaggerated) SBR and a bladder contraction following suprapubic tapping, may constitute a real functional outlet obstruction giving incomplete or complete retention in some suprasacral bladders. In normal subjects, SBR can be considered as a continence reflex with increase of perineal tone following the stimulation of the bladder wall tenso-receptors during stress. PMID- 11788114 TI - [Reiterated intravesical instillation of capsaicin in neurogenic detrusor hyperreflexia: a 5-years experience of 100 instillations]. AB - INTRODUCTION: Capsaicin is a topic and specific C-fiber afferent neurotoxic. After spinal-cord injury, C-fiber afferent proliferate in the bladder mucosae and are involving in detrusor hyperreflexia AIM OF THE STUDY: To investigate middle term efficacy and tolerance of intravesical instillation of capsaicin in spinal cord injured patients presenting severe urinary incontinence refractory to usual therapy due to detrusor hyperreflexia. METHODS: Thirty patients receveid a first intravesical instillation of 1mMol/L Capsaicin solution in 30% alcohol. The efficacy (voiding diary, pads, quality of life, maximum cystometric capacity, maximum detrusor pressure, first and normal desire to void) and tolerance were evaluated before, 1 month and 3 months after each instillation, completed by anual cystoscopy. In patients who responded favorably to this instillation, repeated instillations were proposed when symptoms recurred. RESULTS: 25 patients (83.3%) were improved after the initial instillation (decrease of incontinence frequency-urgency, best quality of life, rise on maximal cystometric capacity), since the 15(th) day and for 3.2 months. 76 reiterative instillations were performed in 22 patients (2 to 9 instillations per patient). 91.2% of them remained successfull, during an average period of 4.2 months. It does not appear loss of benefits after iterative instillations. Transient and moderate adverse effects followed 86% and 79% of the first and reiterated instillation (exacerbation of incontinence, supra-pubic pain). Two patients have presented a begnin and transient inflammatory cystitis after reiterated instillation. DISCUSSION-CONCLUSION: Intravesical instillation of capsaicin are an effective treatment for incontinence and associated symptoms caused by neurogenic detrusor hyperactivity. Propositions to improve immediate tolerance are debated. PMID- 11788115 TI - [Long term outcome of a severe non fluent aphasia. The effect of prolonged rehabilitation]. AB - INTRODUCTION: Long-term clinical outcome of severe non-fluent aphasia is poorly reported. The efficacy of intensive speech therapy has been previously demonstrated but not the efficacy of prolonged speech rehabilitation. METHOD: We report a single case of aphasia, with a description of the initial clinical features and the long term outcome. Moreover we discuss the rehabilitation efficacy in two situations : delayed rehabilitation and long-lasting rehabilitation. RESULTS: A young adult was admitted after fronto-temporal cerebral infarction and presented with a severe non fluent aphasia. Spontaneous recovery involved comprehension but not verbal expression. Speech therapy began 10 months after onset and an improvement of oral expression was observed during at least 6 years. DISCUSSION: This case illustrates long term-recovery patterns of aphasia and the efficacy of delayed speech therapy, and moreover its efficacy at a long time after onset. No rehabilitation was performed during the period of spontaneous recovery. Consequently recovery of spontaneous oral expression can be attributed to speech rehabilitation. Furthermore long-lasting improvement can also be attributed to prolonged rehabilitation. Total amount of speech therapy for the patient can be similar to the amount of efficacious intensive therapy previously described. CONCLUSION: These findings confirm the efficacy of speech therapy in the late stage of recovery, and the possibility of late improvement after stroke. PMID- 11788116 TI - [A forward leaning posture affects more the amplitudes of the centre of pressure displacements than those of the centre of gravity]. AB - OBJECTIVE: An ordinary and practical method to assess the postural control mechanisms is to measure, through a force platform, the point of application of the resultant reaction forces. The recorded signal, the centre of pressure CP, is used to compute the motions of the vertical projection of the centre of gravity (CG(v)) and those of the difference CP-CG(v). The former is considered in this postural task as the controlled variable whereas the latter is thought to express the ankle resultant stiffness. Interestingly, the CG(v) motions can be extracted from the CP trajectory through a simple mathematical model. MATERIALS AND METHODS: The relationship between CP and the elementary motions CP-CG(v) and CG(v) has been tested in the present study by comparing the postural effects induced by a leaning forward position to a normal one consisting to stand still. RESULTS: A large increase is noticed for the amplitudes of the CP-CG(v) motions for both medio-lateral ML and antero-posterior AP directions. On the other hand, a similar effect appears for the CG(v) motions but only on the ML direction. Nevertheless, the frequency analysis indicates that the constancy of the CG(v) motions on the AP direction is accompanied by a change in the frequency distribution, as assessed by the MPF parameters. DISCUSSION-CONCLUSION: These features highlight the necessity, to interpret rigorously the postural performance, to take into account in separate ways each of the elementary CP CG(v) and CG(v) motions which, combined, constitute the CP displacements. PMID- 11788117 TI - [Knee orthosis. First part : evaluation of physiological properties based on a review of the literature]. AB - INTRODUCTION: The aim of this work was to proceed to a literature review to determine the physiological justifications underlying knee orthosis use in medical practice. METHOD: An analysis of the international literature relating to the years 1980-2000 was carried out with the Medline data bank. We added extra articles focusing on the validity of the protocols used in the different evaluations. RESULTS: Five hundred and twelve articles were selected and 46 articles of experimental validation were retained. The experimental protocols are divided into in vitro studies and clinical studies carried out in both healthy subject and patients. Only the in vitro experimental data allowed to reach strain values simulating traumatisms of the articular structures. They allowed to define the interest and limits of the orthosis according to articular physiology. Measurements carried out in vivo were effective to characterize the parameters of stability and proprioception and to discriminate between the orthosis. These studies correspond to experimental situations with related constraints that remain far below lesional constraints, focusing on their clinical validity. CONCLUSION: This work point out many studies focusing on the physiological characterization of the knee orthosis. This evaluation of the orthosis through a single methodology remains difficult and justifies confrontation with clinical trials data. PMID- 11788118 TI - [Influence of age and physical activity on isokinetic characteristics of hamstring and quadriceps muscles of young gymnasts and soccer players]. AB - OBJECTIVE: The aim of this work is the assessment of age and sport influences on the isokinetic knee muscle characteristics. SUBJECTS AND METHOD: Subjects performed a bilateral knee flexion/extension test on an isokinetic device at 60 and 180 degrees.s(-1) speed in concentric mode. The three parameters studied in this work were the Peak Torque, Average Power and hamstring/quadriceps ratio. Thirty-eight soccer players (16,6 +/- 1.4 years old) and 22 gymnasts (18 +/- 2.8 years old) were tested. The population was separated into three groups : 15 years old, 17 years old, 20 years old. RESULTS: The isokinetic values of soccer players were significantly higher (p < 0.0001) than those of the the gymnasts. The isokinetic values of the oldest soccer players were significantly higher (0.005 < p < 0.05) for hamstrings than those of the younger soccer players. The isokinetic values of the oldest gymnasts were significantly higher (0.005 < p < 0.05) for the quadriceps than those of the younger gymnasts. There were no significant differences between dominant and non dominant limbs in soccer players. CONCLUSION: In the present study, the muscular maturation improves the absolute strength of the older sportsmen in comparison to the younger. Soccer favor most the absolute strength of the inferior member in comparison to the gymnastics. PMID- 11788119 TI - [Effect of spasticity on functional capacity in spinal cord injuries: value of visual analogue scale (preliminary study)]. AB - OBJECTIVES: Assessment of the influence of spasticity on activities of daily living in spinal cord injuries. MATERIAL AND METHODS: Fifteen patients with spinal cord injuries have been submitted to a clinical examination and functional assessment by FIM. They answer to a questionnaire on the influence of spasticity on 11 activities of daily living (response by visual analogic scale). RESULTS: The impact of spasticity in daily life is weak (evaluation of difficulties less than 3 on 10 for 7 of the 11 activities of daily living), except for transfers and precision motions when it is on superior limbs. Spasticity has never been considered as useful by patients (VAS less than 3 for 13 persons). DISCUSSION: This study discusses about the real functional influence of spasticity in daily life. It shows the insufficiency of currently used scales and their lack of sensibility to detect the effects of spasticity in daily life's activities. CONCLUSION: Further outcome studies are required to assess the functional role of spasticity in neurologic patients and the real interest of treatments. PMID- 11788120 TI - [MRI and leg stump neuroma]. AB - OBJECTIVE: To describe RMI aspects of leg stump neuroma and to evaluate RMI scan interest for neuroma diagnosis and management. POPULATION AND METHOD: During a 2 years period, 224 amputated patients consulting for pain or prostetics problems were studied. In 10 cases, a characteristic pain leads to neurona diagnosis. This is described as a sensation of ascending or descending electric shock induced by the stimulation of an identified point with a reproducible topography. In all these cases, RMI scans were performed. In thirty two other cases, a RMI scan was performed to confirm a pathology (bursitis, bone abnormality) or in order to establish an etiologic diagnosis. Twelve neuromas were diagnosed. RESULTS: RMI scan showed a neuroma in the ten cases with a clinical suspicion and two asymptomatic neuromas were diagnosed out of the 32 patients without clinical suspicion. Medium delay between amputation and neuroma diagnosis is 11,6 year. In six cases, staking was modified and in six other cases, surgery was necessary. In aIl cases, clinical manifestations disappeared. Vanous RMI aspects ofneuromas are described and illustrated. Neuroma is observed on the extremity of a nerve that have a wavy aspect on its top. The neuroma is an oblong structure, with clear limits. There is an hyposignal with Ti sequence and variable signal with T2 and after gadolinium injection. DISCUSSION: RMI scan is a good way to diagnose amputee neuroma. It makes it possible to demonstrate the pathological character of the neuroma. It has to be performed when a neuroma is suspected. It enables to confirm the diagnosis and establish the exact topography and anatomic connection. Mechanical strains role as a factor of discovering the neuroma is discussed because of the concomitant evolution of associated lesions (bursitis, bone edema). Surgical repair takes place after correcting abnormal mechanical strains. PMID- 11788121 TI - [Early surgery management of pelvic region pressure ulcers versus directed cicatrization in a population of spinal cord injured patients]. AB - OBJECTIVE: To estimate the benefit brought by an early surgery management of pelvis region pressure ulcers compared to medical processing in a population of subjects spinal cord disabled. MATERIAL AND METHOD: The studied population consist of 53 patients (62 pressure ulcers) divided into two groups: the group 1 includes 30 patients (34 pressure ulcers) presenting pressure ulcers stage III or IV (NPUAP scale) with early surgery management, included consecutively during a period of 2 years; the group 2 includes 23 patients (28 escarres) included in a retrospective way, with medical processing by the same team of care. The criteria of judgment are the delay of healing and the delay of delivery of the station sat in the armchair. RESULTS: In the group 1, the average delay of healing is of 42 days and the average delay of delivery for the armchair of 39 days. In the group 2 healing can be obtained only in 13 cases and in an average delay of 180 days. Differences are significant (p < 0.05). DISCUSSION - CONCLUSION: The originality of this study results in the comparison of two processing within two groups of patients having close demographic characteristics. It clearly shows the interest of the early surgery of the pelvic pressure ulcers comparing to medical processing and illustrates the requirement for a close cooperation between teams specialized in plastic surgery and teams specialized physical medicine. PMID- 11788123 TI - Managing the risk of atherosclerosis: the role of high-density lipoprotein. AB - The association of low levels of high-density lipoprotein cholesterol (HDL-C) with an increased incidence of cardiovascular events implies a central involvement of high-density lipoprotein (HDL) in the retardation of the atherosclerotic process and the corresponding slowing of progression of coronary artery disease. HDL-C appears to exert this protective effect through multiple mechanisms. Through its association with antioxidant enzymes, such as paraoxonase and the platelet-activating factor acetylhydrolase, it may protect low-density lipoprotein (LDL) from oxidation and decrease the expression of adhesion molecules, both of which contribute importantly to the initiation of atherosclerotic plaques. HDL may also further inhibit plaque expansion by improving the stability of existing plaques, and it may reduce the susceptibility of plaques to rupture by mediating reverse cholesterol transport. This article examines recent experimental approaches aimed at elucidating these antiatherogenic, HDL-mediated mechanisms. PMID- 11788124 TI - Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. AB - Plasma high-density lipoprotein cholesterol (HDL-C) is inversely related to coronary artery disease incidence in both women and men, with a proportionately increasing effect of HDL-C throughout the average (or slightly above average)-to low concentration range. A substantial body of evidence from major epidemiologic studies has established that this coronary artery disease risk associated with HDL-C is entirely independent of plasma low-density lipoprotein cholesterol, other lipid parameters (triglycerides, total cholesterol), and other nonlipid risk factors. The coronary artery disease relative risk for patients with low levels of HDL-C in conjunction with low total cholesterol is also markedly higher than in patients with a profile of high levels of these 2 lipid parameters. Similarly, the risk associated with a low HDL-C level is of particular significance in patients with established coronary artery disease or with type 2 diabetes, and it is a more pertinent factor to consider when managing dyslipidemia. PMID- 11788125 TI - The relative role of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in coronary artery disease: evidence from large-scale statin and fibrate trials. AB - Statin therapy has been remarkably successful in reducing coronary events and improving survival. Reduction in low-density lipoprotein cholesterol (LDL-C) is the paramount mechanism for the benefit of statins. Although the relation between reduction of risk of coronary artery disease and pretreatment lipid levels has not been fully resolved, a feature of statin therapy emerging from previous large scale trials is the diminished benefit when the baseline level of LDL-C is low (eg, <125 mg/dL). Increases in levels of high-density lipoprotein cholesterol (HDL-C) with statin therapy are associated with mild reductions in coronary events, indicating that HDL-C is an important element. However, the risk of low HDL-C is not altered by statin therapy, in marked contrast with LDL-C. Because most coronary events have not been prevented in the statin trials, nonstatin lipid therapy, including fibrates, may be necessary to further reduce the unacceptably high rate of coronary artery disease. PMID- 11788126 TI - Targeting low high-density lipoprotein cholesterol for therapy: lessons from the Veterans Affairs High-density Lipoprotein Intervention Trial. AB - Results of the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA HIT) showed that therapy with the fibric acid gemfibrozil significantly reduced the incidence of coronary artery disease events in men with known coronary artery disease and a low level of high-density lipoprotein cholesterol (HDL-C). Coronary artery disease event reduction was inversely related to levels of HDL-C achieved with gemfibrozil and, even at relatively low concentrations of HDL-C, coronary artery disease event reduction with gemfibrozil was significantly greater than with placebo. Subjects with a low HDL-C level who were recruited for VA-HIT had a high prevalence of features of the metabolic syndrome with obesity, type 2 diabetes, and hyperinsulinemia. These individuals especially benefited from gemfibrozil, and thus, fibrate therapy may have an increasing role in reducing coronary artery disease risk in a setting of an increasing worldwide prevalence of obesity and diabetes. PMID- 11788127 TI - Peroxisome proliferator-activated receptor-alpha activation and high-density lipoprotein metabolism. AB - Recently, considerable progress has been made in understanding the molecular basis of lipoprotein metabolism, including the role of peroxisome proliferator activated receptor (PPAR)-alpha--the specific transcription factor which, when activated, influences the expression of genes encoding for proteins involved in high-density lipoprotein (HDL) metabolism. Because the fibrates have a direct effect on PPAR-alpha and, in turn, on 5 key genes that determine lipoprotein structure and function, they are able to exert a multiple influence on HDL metabolism. Increased HDL synthesis, accelerated efflux of cholesterol, and its hepatic uptake are the ultimate outcome of fibrate influence, with a consequent enhancement of the protective effect of HDL cholesterol. PMID- 11788129 TI - Treating lipid abnormalities in patients with type 2 diabetes mellitus. AB - The typical lipid levels in type 2 diabetes mellitus are low high-density lipoprotein cholesterol, normal low-density lipoprotein cholesterol, and high triglycerides. Atherosclerotic cardiovascular disease is the most common problem confronting those with type 2 diabetes mellitus. Some previous large lipid lowering clinical trials conducted subanalyses of individuals with type 2 diabetes. Although these trials suggested a coronary benefit, questions remained because of (1) the limitations of such subanalyses, (2) the atypical characteristics of the populations, and (3) some inconsistencies in their findings. The Diabetes Atherosclerosis Intervention Study (DAIS), a randomized, double-blind, placebo-controlled study in men and women with type 2 diabetes, has demonstrated by quantitative angiography that treatment with micronized fenofibrate corrected their lipid abnormalities and reduced the progression of coronary disease. Furthermore, this occurred in individuals with lipid levels that many physicians would consider to be normal. PMID- 11788128 TI - Increasing high-density lipoprotein cholesterol: an update on fenofibrate. AB - The inverse relation between coronary artery disease and the concentration of high-density lipoprotein cholesterol (HDL-C) is well established. A low HDL-C concentration is frequently accompanied by the features of the metabolic syndrome found in patients with type 2 diabetes and in individuals who are abdominally obese. Results from 3 independent trials are consistent in showing that fenofibrate is able to increase HDL-C levels across a wide range of dyslipidemic states. The HDL-C-increasing effect of fenofibrate is proportionately greater when baseline levels are low. Comparing results from published trials, the absolute increase in HDL-C produced by fenofibrate is greater than that with statins across all baseline HDL-C levels, and a 40-mg/dL treatment target HDL-C level is more likely to be achieved with fenofibrate therapy. Fenofibrate has favorable pleiotropic effects on several features of the metabolic syndrome, which are likely to explain the clinical benefits of fibrate therapy, beyond an impact on HDL-C levels. The additional reciprocal beneficial effect of fenofibrate in lowering low-density lipoprotein cholesterol (LDL-C) benefits those patients with low HDL-C and moderately increased LDL-C; the American Diabetes Association now recommends fibrate therapy in this case. Another trial, the Diabetes Atherosclerosis Intervention Study (DAIS) has also provided angiographic evidence to show that fenofibrate treatment may slow coronary artery disease progression in type 2 diabetes. Treatment effects on apolipoproteins suggest that not all fibrates affect HDL-C to an equal degree. A trial with fenofibrate focusing on coronary artery disease risk and mortality reduction in patients with type 2 diabetes that is currently under way, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial is expected to report in 2005. PMID- 11788130 TI - High-density lipoprotein cholesterol and treatment guidelines. AB - Setting consistent guidelines for the treatment of lipid abnormalities must take into consideration several factors and must balance the need for precision (favored by specialists) and practicality in the patient setting (favored by general medical practitioners). The appropriate populations for treatment should be clearly defined, and usual threshold levels, target levels, and treatment should be well established. Plasma high-density lipoprotein cholesterol (HDL-C) has not been widely incorporated in guidelines as a significant abnormality predictive of cardiovascular risk and as a therapeutic target. However, that view is changing in the light of recent improved understanding of the importance of each lipid fraction abnormality, including HDL-C, in the pathophysiology of atherosclerotic disease. In addition, clinical trials have demonstrated the apparent benefit of increasing low levels of HDL-C in reducing cardiovascular events. The use of guidelines incorporating threshold and target levels for managing HDL-C in high-risk populations is becoming seen as a practical means of improving the outcome for patients, especially for special groups, such as the elderly and those with type 2 diabetes mellitus. PMID- 11788131 TI - Influence of levels of carbon dioxide and oxygen upon gasping in perfused rat preparation. AB - In vivo, the augmenting pattern of integrated phrenic nerve discharge of eupnea is altered to the decrementing pattern of gasping in severe hypoxia or ischaemia. Identical alterations in phrenic discharge are found in perfused in situ preparations of the juvenile rat. In this preparation, gasping was produced by equilibration of the perfusate with various levels of carbon dioxide and oxygen. The duration of the phrenic burst, the interval between bursts and the burst amplitude were not significantly different following equilibration with 21-6%O(2) at 5% CO(2) or with 0-9% CO(2) at 6% O(2), with the exception that the burst amplitude was significantly greater in hypercapnic-hypoxia (9% CO(2) at 6% O(2)). It is proposed that hypoxia-induced gasping results from the release of an endogenous pacemaker activity of rostral medullary neurons. This release is caused by cellular mechanisms that change the balance between membrane ionic currents. Moreover, these cellular mechanisms may be explicitly induced by alterations in the ionic and metabolic homeostasis. PMID- 11788132 TI - CO(2)-induced c-Fos expression in hypothalamic vasopressin containing neurons. AB - Following exposure of anesthetized and unanesthetized rats to hypercapnic stress, arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei were examined for expression of the c-fos gene encoded protein (c-Fos). In addition, we determined whether AVP-containing PVN neurons activated by hypercapnia project to phrenic nuclei. In adult control rats, only scant c-Fos-like immunoreactive neurons were observed within the hypothalamic nuclei. A marked increase in c-Fos positive cells was induced after 2 h of breathing a gas mixture with elevated CO(2) (5% CO(2), 21% O(2) and 74% N(2), or 1 h following breathing of 12% CO(2,) 21% O(2,) and 67% N(2)). Colocalization studies of AVP and c-Fos protein revealed that in the PVN, 75% of AVP-containing cells expressed c-Fos immunoreactivity. c-Fos and AVP were coexpressed in 60% of SON neurons in anesthetized rats. In addition, retrograde labeling studies with cholera toxin b subunit (CTb) revealed that a subpopulation of PVN cells (15%) that project to phrenic nuclei are activated by hypercapnia, as indicated by c-Fos expression. These results indicate that (i) PVN and SON AVP containing neurons are part of the neuronal networks that react to hypercapnic exposure; and (ii) a subset of CO(2) reactive PVN cells innervate phrenic nuclei. PMID- 11788133 TI - The circadian pattern of breathing in conscious adult rats. AB - Recently, a circadian oscillation in pulmonary ventilation (VE) was reported in conscious, undisturbed rats [Respir. Physiol. 120 (2000) 179], with a pattern similar to that of body temperature (Tb), oxygen consumption (V(O(2))) and activity. The present study explored the relationship between the daily VE pattern and these rhythms. Adult rats (n=23) were instrumented for measurements of Tb and activity by telemetry, and placed in a chamber for measurement of VE by the barometric method and V(O(2)) by an open-flow method. Simultaneous recordings were made continuously for 3 consecutive days in a 12-h light:12-h dark (L:D) cycle. All variables showed substantial daily oscillations, with significantly higher values in the D phase, and approximately proportionate changes in VE and V(O(2)). Daily changes in tidal volume (VT) relative to inspiratory time (TI), rather than in TI relative to total breath duration, accounted for the oscillation in VE. The VT rhythm was phase-advanced relative to those of V(O(2)) and Tb. L-D differences in VE persisted when comparison between the phases was made for the same level of either very low or very high activity. We conclude that the oscillation in VE does not depend on the daily changes in activity. Rather, the daily pattern of VE is likely shaped by the oscillations of multiple physiological variables, two of which may be Tb and V(O(2)). PMID- 11788134 TI - Metabolic and ventilatory responses to CO hypoxia at different levels of oxygenation in the rat. AB - Adult, conscious rats have been exposed to CO-induced hypoxia for 30 min in normoxia, ambient hypoxia (FI(O(2))=14%), or hyperoxia (FI(O(2))=40%). From arterial blood gas analyses, FICO was adjusted in all experimental conditions to obtain final arterial oxygen saturations (Sa(O(2))) of approximately 60%. Oxygen uptake (V(O(2))), ventilation (V) and colonic temperature (Tc) were measured in experiments carried out at an ambient temperature of either 25 or 15 degrees C. It was found that CO hypoxia induced marked reductions in the hemoglobin O(2) half saturation pressure (P(50)). Furthermore, isolated reductions in Sa(O(2)) (with Pa(O(2)) constant) induced decreases in V(O(2)) and Tc and increases in ventilation which, as compared with normoxia, were enhanced in ambient hypoxia and reduced but still significant in hyperoxia. As suggested by previous studies, the interactions between Sa(O(2)) and Pa(O(2)) which operate on the control of metabolism and ventilation originate probably in the central nervous system. PMID- 11788135 TI - Effects of neural drives on breathing in the awake state in humans. AB - We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne-Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P(CO(2)) with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P(CO(2)) over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness changes, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep. PMID- 11788136 TI - Comparison between anatomy and resistance of upper airway in normal subjects, snorers and OSAS patients. AB - Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone. PMID- 11788137 TI - Mechanisms of ventilation inhomogeneity during vital capacity breaths standing and supine. AB - Overall inhomogeneity of ventilation distribution, as measured by single-breath vital capacity (VC) washout (SBW) is known to be greater supine vs. standing. To establish the underlying mechanisms 13 healthy males performed VC SBW of 4% SF(6) and He, standing and supine, with or without a 10 sec breathhold (BH). Overall inhomogeneity, as indicated by normalized phase III slopes, was >50% greater supine (SF(6) 13.1 x 10(-3); He 10.7 x 10(-3) L(-1)) than standing (SF(6) 8.6 x 10(-3); He 6.4 x 10(-3) L(-1); P<0.001). The (SF(6)-He) slope, an index of intraacinar inhomogeneity, did not change with posture. Breathholding, assumed to eliminate convective dependent inhomogeneity within and/or between small lung units, produced twice as great reduction of inhomogeneity when supine vs. standing. After BH inhomogeneity remained significantly greater supine vs. standing. In conclusion, at least two events seem to underlie the increased inhomogeneity when supine: (1) a substantially increased convection dependent non uniformity between well-separated lung regions; and (2) a somewhat increased convection dependent non-uniformity within and/or between peripherally located lung units. PMID- 11788138 TI - Eicosanoids modulate hyperpnea-induced late phase airway obstruction and hyperreactivity in dogs. AB - A canine model of exercise-induced asthma was used to test the hypothesis that the development of a late phase response to hyperventilation depends on the acute production of pro-inflammatory mediators. Peripheral airway resistance, reactivity to hypocapnia and aerosol histamine, and bronchoalveolar lavage fluid (BALF) cell and eicosanoid content were measured in dogs approximately 5 h after dry air challenge (DAC). DAC resulted in late phase obstruction, hyperreactivity to histamine, and neutrophilic inflammation. Both cyclooxygenase and lipoxygenase inhibitors administered in separate experiments attenuated the late phase airway obstruction and hyperreactivity to histamine. Neither drug affected the late phase inflammation nor the concentrations of eicosanoids in the BALF obtained 5 h after DAC. This study confirms that hyperventilation of peripheral airways with unconditioned air causes late phase neutrophilia, airway obstruction, and hyperreactivity. The late phase changes in airway mechanics are related to the hyperventilation-induced release of both prostaglandins and leukotrienes, and appear to be independent of the late phase infiltration of inflammatory cells. PMID- 11788139 TI - Type I nitric oxide synthase in the human lung is predominantly expressed in capillary endothelial cells. AB - Nitric oxide (NO) has important functions in the regulation of pulmonary smooth muscle tone. In the human lung, published data on the expression and distribution of neuronal nitric oxide synthase (NOS-I) are contradictory. The aim of this study, therefore, was to determine the predominant cells expressing NOS-I in the human lung. Immunofluorescence double staining techniques were applied to normal human lung tissue using established monospecific antibodies directed against NOS I. Suprisingly, capillary endothelial cells in the alveolar septa were identified as the major sites of NOS-I expression. Neither alveolar nor bronchiolar epithelium, nor the alveolar macrophages, expressed NOS-I. These results indicate that the predominant sites of NOS-I expression in the human lung are confined to non-neuronal, i.e. capillary endothelial cells and suggest a role for NO in the regulation of pulmonary endothelial cell permeability. PMID- 11788140 TI - Brain electrical activity during combined hypoxemia and hypoperfusion in anesthetized rats. AB - In order to investigate the effects of moderate hypoxemia on brain electrical activity and the consequences of an altered cerebro-vascular response to hypoxemia, we recorded changes in electrical activity of the brain in anesthetized rats following unilateral carotid artery ligation (UCAL). In these animals, on the clamped side, cerebral blood flow, whilst normal during normoxia, shows less augmentation during hypoxemia. Six anesthetized (Halothane) Sprague Dawley rats with UCAL were studied during 20 min periods of baseline (FI(O(2))=30%), hypoxemia (FI(O(2))=9.5%) and recovery (FI(O(2))=30%): mean arterial pressure of oxygen (PA(O(2))) achieved was 177.0, 37.6 and 160.1 mmHg, respectively. A significant decrease in the frequencies of the ECoG was observed bilaterally during hypoxemia: centroid frequency (fc)=3.37+/-0.14 and 2.85+/-0.13 Hz on the intact and clamped hemisphere respectively during hypoxemia versus fc=4.09+/-0.20 Hz (mean+/-S.E.M.) during baseline, which was not reversed during recovery (3.27+/-0.11 Hz) (ANOVA, P<0.01). The total power of the signal (Pw) was unaffected on the intact hemisphere but diminished on the clamped side during hypoxemia. Our results show that a significant slowing of ECoG is observed during hypoxemia of moderate intensity (40 mmHg) even when cerebro-vascular response to hypoxemia is preserved and that total power of the ECoG signal is severely diminished when the cerebro-vascular response to hypoxemia is impaired. PMID- 11788141 TI - Effect of regional changes to shell conductance on oxygen consumption and growth of chicken embryos. AB - Diffusive and perfusive gas conductances of the shell and chorioallantois of avian eggs are not homogeneous, leading to disequilibrium between the air cell gas and chorioallantoic venous blood. This study measured the embryonic ability to maintain oxygen consumption rate and growth under experimentally enhanced inhomogeneity of diffusive conductance, achieved by waxing half of the eggshell and exposing the other half to graded hyperoxia that doubled the oxygen gradient across the shell. Thus, the overall gas conductance was effectively normal but highly inhomogeneous. No differences were observed between the experimental and the control eggs in respiration, residual yolk or embryo growth rate from day 12 until day 20. The embryo was able to utilise the increase of oxygen in the environment to compensate for the loss of about half of its respiratory surface area under the wax. The results indicate that an even distribution of pores in the eggshell and uniformity of chorioallantoic perfusion are not required for successful avian development. PMID- 11788142 TI - Updating concepts of first branchial cleft defects: a literature review. AB - OBJECTIVE: The Sinuses and fistulae of first branchial cleft origin have been widely reported in the literature and their variable relationship to the facial nerve has been described. Most published series however are too small to allow a detailed analysis of the relative frequency of various relationships of these lesions to the facial nerve and therefore enabling the determination of risks to the nerve at surgery. The aim of this study was to perform a comprehensive review of literature in an attempt to identify those patients with a deep tract (lying deep to the main trunk of the facial nerve and/or its branches, and/or between the branches) and to recognize the incidence of the complications of surgical management. METHODS: Available English, French and German literature between 1923 and 2000 was reviewed and variables including patient's age, sex, side and type of anomaly, opening of the lesion and the relationship of the tract are analyzed in relation to the position of the facial nerve. The complications due to their surgical excision are also reported. RESULTS: Of the total number of cases with fistulae and sinuses identified (n=158) fistulous tracts were more likely to lie deep to the facial nerve compared with sinus tracts (P=0.01). Lesions with openings in the external auditory meatus are associated with a tract superficial to the facial nerve (P=0.05). Patients presenting at a younger age were more likely to have a deep tract with consequent increased risk of facial nerve damage. CONCLUSION: Identification of the facial nerve trunk at an early stage of dissection is critical. Extra care and caution should be exercised in younger patients (<6 months), those with fistulous tracts and in patients with a tract opening elsewhere other than the external auditory canal. PMID- 11788143 TI - Imaging and surgical approach of nasal dermoids. AB - OBJECTIVE: Determine the most accurate and cost effective radiographic evaluation for nasal dermoids. Determine the best surgical approach for excision of nasal dermoids. DESIGN: Retrospective chart review. SETTING: Division of Pediatric Otolaryngology, Children's Hospital and Health Center, San Diego, California. PARTICIPANTS: All patients with nasal dermoids evaluated and treated from 1990 to 2000. INTERVENTION: Preoperative radiographic evaluation and surgical excision. OUTCOME MEASURES: Accuracy of CT and MRI correlated with surgical findings and results. RESULTS: Ten patients were identified with the diagnosis of nasal dermoid. The age at diagnosis ranged from 0 to 24 months, with a mean of 3 months. Six children presented with masses located at the glabella, three patients presented with masses located at the nasal dorsum and one presented with a mass at the nasal tip. Six children underwent a computed tomogram with contrast of the head. Seven children underwent a MRI study of the head. Three children underwent an initial CT followed by MRI. Twenty percent of children were found to have intracranial extension. CT scan accurately diagnosed intracranial extension in one case, was indeterminate in a second case and falsely positive in a third case. MRI correctly diagnosed intracranial extension in two cases and had no false positive or false negative results. No children were found to have associated intracranial anomalies. In the early years of the review, a simple excision was made over the mass with blunt and sharp dissection for removal. (An external rhinoplasty incision is now used with better exposure and improved cosmetic results.) In cases with intracranial communication, a combined approach of external rhinoplasty and craniotomy was used. CONCLUSIONS: MRI alone is the most cost effective and accurate means of evaluating nasal dermoids and is essential for preoperative planning. The surgical approach of choice is external rhinoplasty for both cosmetic reasons and exposure of nasal dermoids with and without intracranial extension. PMID- 11788144 TI - Tracheobronchial rupture: a considerable risk for young teenagers. AB - Tracheobronchial (TB) ruptures are ten times lower in children than in adults. Despite its rarity in the literature, we found that it is as common as in adults in our series. We investigated TB ruptures in childhood regarding age, trauma presentation, injury localization and treatment options. From 1994 through 2001, eight children (six male, two female) were admitted to our department with TB injury. All patients were healthy prior to trauma. The average and median ages were 9.8 and 11, respectively. All patients except one (iatrogenic) were suffering from blunt thoracic trauma. There were seven main bronchial (five right, two left) and one tracheal wounds. Six of the ruptures were circumferential. Urgent (n=6) and delayed (n=2) thoracotomies were performed; 'end-to-end' anastomosis (n=4), pneumonectomy (n=2) and 'primary suturing' (n=2) were applied. We had no mortality. Main bronchus rupture was overlooked in two patients as one of them had almost totally normal clinical appearance, and the other one had negative endoscopic findings. Both of these patients were successfully operated within 3 months. Our limited experience showed us that these kinds of injuries threaten school age population as well. False negative bronchoscopic results increase when additional injuries accompany. TB ruptures should be always taken into consideration after blunt chest trauma. Early or late repair of the lesion should be decided depending on the patient's clinical course. PMID- 11788145 TI - Otitis media in children: seasonal changes and socioeconomic level. AB - OBJECTIVE: Our objective was to determine the frequency of otitis media (OM) in relation to socioeconomic and seasonal factors in a city in southern Brazil. METHODS: A prospective, longitudinal study was carried out with a 3-4-year-old cohort of children randomly selected in schools serving populations of higher socioeconomic status (AB; monthly family income >10 minimum wages, US$ 1000) or lower socioeconomic status (CD; monthly family income < or = 3 minimum wages, US$ 300). The children were assessed in the fall, winter, and spring of 1997 using otoscopy and tympanometry. RESULTS: Among 156 children who finished the study, 53.8% belonged to socioeconomic group CD. Otoscopy suggested chronic suppurative otitis media (OM) (tympanic membrane perforation or otorrhea) in <6% of children in the CD group, with no seasonal variation. Alterations suggesting secretory otitis media (SOM) were significantly more frequent in the CD group (P< or = 0.001), with a peak in the winter. The prevalence of SOM on otoscopy was: fall (20.9% AB; 38.1% CD); winter (28.6% AB; 81% CD), and spring (23% AB; 49.3% CD). The incidence of SOM in the winter according to tympanometry was 18.4% (group AB) and 72.9% (group CD). Among children with a normal tympanogram in the fall, 44.7% presented a type B tympanogram (presence of middle ear effusion) in the winter. Only 17.6% still presented a type B tympanogram in the spring. From the ears with type B tympanogram in the fall, 80% had the same result in the winter, and 60.9%, in the spring. A sharp seasonal SOM peak was observed in the CD group in the winter. CONCLUSION: Children in the lower socioeconomic group have a peak incidence of serous otitis media (OM) in the winter. Presence of type B tympanogram in the fall and belonging to socioeconomic group CD are indicators of poor prognosis in terms of the spontaneous resolution of SOM. PMID- 11788146 TI - Predicting the development and outcome of otitis media by tympanometry. AB - OBJECTIVE: Identification of children with high risk of development or prolongation of otitis media would be highly useful in clinical practice. In this study, tympanometry was assessed for its capability in predicting development and resolution of acute otitis media (AOM). METHODS: Visits of 329 children followed in the Finnish Otitis Media Cohort Study from 2 to 24 months of age were evaluated for this report. Tympanometry was routinely performed on all children during their visits to a special study clinic. Adjacent consecutive visits were used for analysis of development and resolution of middle ear fluid (MEF) between the visits. Descriptive analysis utilized all data obtained during the longitudinal follow-up; confirmatory statistical analysis was performed on data of one randomly selected visit per subject to ensure independence of observations. Presence of MEF at the second visit was used as the outcome. RESULTS: Negative tympanometric peak pressure (<-100 daPa) was found to predict the development of otitis media when observed during respiratory infection with no concomitant ear disease. Otitis media developed within 20 days to 40% of children with negative pressure compared with 20% of children without negative pressure. The observed association was confirmed statistically (odds ratio 4.8, 95% confidence interval 2.4-9.6). Poor outcome of AOM at the subsequent follow-up visit 3-5 weeks later was found in 9% of ears with negative pressure tympanogram compared with 24% with initial type B or normal pressure tympanogram during AOM. However, we could not confirm the finding in statistical analysis (odds ratio 0.6, 95% confidence interval 0.2-2.0). CONCLUSIONS: Profound negative tympanometric peak pressure is a significant marker of increased risk for development of otitis media. Children with negative pressure have to be thoroughly followed for subsequent progress of the respiratory disease and development of otitis media. For the prediction of resolution of AOM, the findings remained inconclusive. PMID- 11788147 TI - The effect of ketoprofen on recovery after tonsillectomy in children: a 3-week follow-up study. AB - OBJECTIVE: To evaluate recovery after tonsillectomy in children, and to determine the safety and efficacy of ketoprofen in pain treatment after discharge. STUDY DESIGN: A prospective, longitudinal study in 102 children undergoing tonsillectomy. METHODS: All children underwent tonsillectomy under a same general anesthesia. At discharge, all patients were prescribed ketoprofen capsules at a dose of 3-5 mg(-1) kg(-1) per 24 h for postoperative pain control at home, with paracetamol or paracetamol-codeine tablets for rescue analgesia. At home, the patients recorded pain and analgesic consumption each day for the first week after surgery. At 3 weeks, patients recorded the total analgesic requirement, duration of pain, and all adverse events during recovery and return to normal daily activities. RESULTS: The median of pain cessation was 9 days (range 1-20 days) and the median duration of analgesic treatment was 10 days (4-19 days). More than 50% of the patients needed rescue analgesic daily during the first week after tonsillectomy. Ketoprofen combined with paracetamol or paracetamol-codeine provided sufficient analgesia for most children. However, the analgesic action of drugs was too short to achieve pain relief, which allow undisturbed sleep during the first postoperative nights. A return back to normal daily activities took place after 9 days (2-26 days). The influence of age for pain pattern was negligible. Five patients needed electrocautery to stop postoperative bleeding. No other serious adverse-events occurred. CONCLUSIONS: The main problem after tonsillectomy is significant pain that may last 9 days or longer after surgery. Ketoprofen combined with paracetamol-codeine seems to provide a sufficient analgesia, but before ketoprofen may be recommended for children during tonsillectomy a larger study is needed to show whether or not ketoprofen increases the hemorrhage rate. PMID- 11788148 TI - Better speech performance in cochlear implant patients with GJB2-related deafness. AB - OBJECTIVE: We applied mutation screening in seven cochlear implant users to identify those persons with GJB2-related deafness to determine whether etiology of deafness was predictive of speech performance after implantation. METHODS: Direct sequence of GJB2 was conducted over seven cochlear implant users with prelingual hearing impairment and their speech, language and cognitive performance was examined. RESULTS: The three persons with GJB2-related deafness had a mean vocabulary of 1243 words compared to a mean vocabulary of 195 words in the four children with GJB2-unrelated deafness, although the number of patients examined here was limited. The developmental quotient (DQ) of cognitive ability also was higher in those children with GJB2-related deafness. CONCLUSIONS: These preliminary results suggest that better speech performance after cochlear implantation may be observed in persons with GJB2-related deafness. In the future, detailed phenotypic studies and mutation screening for non-syndromic hearing loss may play an important role in the preoperative assessment of prelingually-deafened children. PMID- 11788149 TI - Nasopharyngeal teratocarcinosarcoma. AB - Congenital germ cell tumors are uncommon. The most common site of origin is in the saccrococygeal region. Teratomas arising from the head and neck comprise a small proportion of this entity, and of these, nasopharyngeal lesions are rare. Also known by various synonyms such as hamartoma and hairy polyp, the teratoma is a well-recognized, and generally benign, clinical and histopathological entity. We present a case of a nasopharyngeal teratocarcinosarcoma associated with a cleft palate and the congenital replacement or absence of the ipsilateral Eustachian tube. PMID- 11788150 TI - Magnetic removal of a nasal foreign body. AB - We describe a case of metallic nasal foreign body removal from a child with the aid of a permanent magnet. This is the first documented case of such a technique as far as we are aware. Magnets may prove invaluable in the removal of metallic nasal foreign bodies particularly in children and avoid the need for a general anaesthetic. A brief review of the use of magnets to remove foreign bodies is included. PMID- 11788152 TI - Congenital cholesteatoma of external auditory canal. AB - A 7-month-old male child is reported with congenital cholesteatoma of the external auditory canal. We describe the clinical features, computed tomography finding and surgical treatment. Congenital cholesteatomas can occur within the temporal bone. There are six places of location: (1) petrous apex, (2) mastoid, (3) middle ear, (4) both middle ear and mastoid, (5) external ear canal and (6) within the squamous portion of the temporal bone. Congenital cholesteatoma of the external auditory canal is rare. Generally, it appears in the canal floor without lesions in the tympanic membrane. Computed tomography completes the study. Treatment consists of excision of the mass. PMID- 11788151 TI - Eosinophilic granuloma of the bilateral temporal bone. AB - An unusual presentation of eosinophilic granuloma (EG) of the bilateral temporal bone in a 2-year-old male child is discussed with the literature review. Involvement of the temporal bone is relatively uncommon and otorrhea or symptoms resembling mastoiditis are nonspecific. This rare condition should be kept in mind in differential diagnosis of otitis media refractory to medical therapy. PMID- 11788154 TI - Deprenyl protects from MPTP-induced Parkinson-like syndrome and glutathione oxidation in rat striatum. AB - An intrastriatal injection with 18.8 nmoles of the neurotoxic agent 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced in rats a progressive parkinsonism characterized by a major loss of striatum dopamine (DA) levels and an increased turnover of this neurotransmitter 96 h after the administration. In addition, the intrastriatal administration of MPTP produced an alteration in various behavioral markers of motor activity. Loss of DA was accompanied by a significant decrease of reduced glutathione (GSH) and an increase in GSH oxidation in the striatum. When deprenyl (10 mg/kg) was i.p. administered 2 h before the intrastriatal injection of MPTP, DA, GSH, glutathione redox status and the indexes of motor activity were not altered. These results show that MPTP increases striatum oxidative stress leading to cellular and in vivo degenerative changes which are prevented by pretreatment with deprenyl. PMID- 11788156 TI - Renal damage, metabolism and covalent binding following administration of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) to male Fischer 344 rats. AB - In vivo metabolism, nephrotoxicity and covalent binding to proteins were evaluated in male Fischer 344 rats that received [2,3-14C]-N-(3,5 dichlorophenyl)succinimide (14C-NDPS). Some animals were pretreated with the enzyme inducer phenobarbital (PB, 80 mg/kg per day, for 3 days, i.p. in saline) prior to receiving a non-nephrotoxic dose of 14C-NDPS (0.2 mmol/kg, i.p. in corn oil). Other rats were pretreated with the cytochrome P450 inhibitor 1 aminobenzotriazole (ABT, 100 mg/kg, 1 h prior to NDPS, i.p. in saline) before administration of a non-toxic or a toxic dose (0.2 or 0.6 mmol/kg, respectively, i.p. in corn oil) of 14C-NDPS. Non-pretreated animals received either dose of 14C NDPS, but did not receive PB or ABT. All rats were sacrificed 6 h after administration of 14C-NDPS. Nephrotoxicity was monitored by measuring urine volume, urine protein concentrations, blood urea nitrogen levels, and kidney weights. The NDPS metabolic profile in tissue, blood, and urine was analyzed by HPLC. Covalent binding of 14C-NDPS-derived radioactivity to tissue proteins was also measured. Compared with non-pretreated rats, PB-pretreatment potentiated the toxicity of the non-toxic dose of 14C-NDPS. In contrast, ABT-pretreatment protected the rats against NDPS nephrotoxicity. The amount of N-(3,5 dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA), an oxidative, nephrotoxic metabolite of NDPS, was elevated in kidney homogenates and urine by PB pretreatment (0.2 mmol/mg NDPS). ABT pretreatment inhibited NDPS metabolism at both doses. Covalent binding of 14C-NDPS (0.2 mmol/kg)-derived radioactivity to renal and plasma proteins was higher in the PB-pretreated rats than in the non pretreated animals. In contrast, ABT-pretreatment partially inhibited covalent binding at both doses of 14C-NDPS. Our results suggest that there is a relationship between oxidative metabolism of NDPS, covalent binding of an NDPS metabolite to renal proteins, and NDPS-induced nephrotoxicity in rats. PMID- 11788155 TI - Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid. AB - Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system. PMID- 11788157 TI - Behavioural effects of tetrachloroethylene exposure in rats: acute and subchronic studies. AB - This study was carried out to compare the neurobehavioural profile of acute and subchronic tetrachloroethylene (perchloroethylene, PCE) exposure in rats. In the acute study, a single bolus of 50 and 500 mg/kg of PCE in corn oil was administered by gavage. In the subchronic experiments, rats were exposed to PCE at a dosage of 5 and 50 mg/kg in corn oil, 5 days per week for 8 weeks. Nociception, locomotion and seizure susceptibility was tested using open-field, tail immersion and hot plate and pentylenetetrazol-induced seizures, respectively. Subchronic PCE exposure exhibited higher antinociceptive effect and lower motor activity in comparison with acute exposure. Pentylenetetrazol-induced convulsion thresholds were elevated following acute PCE exposure. In contrast, subchronic PCE exposure only increased thresholds for myoclonic twitch and face and forelimb clonus without altering the thresholds for running and bouncing clonus and tonic hindlimb extension. These findings suggest that subchronic PCE exposure results in progressively greater toxic effects on nociception and locomotor activity. The differential effects on seizure susceptibility between acute and subchronic exposure may represent different alterations on neural circuits involved in seizure generation. PMID- 11788158 TI - HSP70 overexpression increases resistance of V79 cells to cytotoxicity of airborne pollutants, but does not protect the mitotic spindle against damage caused by airborne toxins. AB - Exposure of Chinese hamster V79 cells to extracts of airborne pollutants induced formation of multipolar or incomplete mitotic spindles. To find out whether overexpression of the HSP70 chaperone protein could protect spindles against airborne toxins we constructed V79 cells stably transfected with an expression vector containing rat heat-inducible hsp70.1 gene under the control of a constitutive CMV promoter. When cells were incubated with extracts of airborne pollutants (5-20 microg/ml) no protective effect of the HSP70 protein against mitotic spindle damage was observed. Moreover, at 20 microg/ml of extracts of airborne toxins the frequency of mitotic malformations was even higher in HSP70 overexpressing cells than in control ones. Extracts of airborne pollutants of 50 microg/ml blocked the formation of mitotic figures both in control and HSP70 overexpressing cells and led to destruction of cell nuclei. However, the HSP70 overproducing cells exhibited higher survival rates when exposed to heat shock and airborne toxins than the control ones, as determined by MTT assay. This suggests that HSP70 overexpression-a frequent feature of cancer cells-should be considered as a factor facilitating survival of cells with damaged mitotic spindles and aberrantly segregated chromosomes. PMID- 11788159 TI - Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats. AB - The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g b.wt.) was orally administered daily to alloxan-diabetic rats for 4 weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (P<0.05) increased in plasma of alloxan-diabetic rats compared with the control group. In contrast, total protein and albumin were significantly decreased by 25 and 46%, respectively, versus control. Treatment of the diabetic rats with repeated doses of any one of the three herb suspensions could restore the changes of the above parameters to their normal levels after 4 weeks of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AlP) activities were significantly (P<0.05) increased in the plasma of alloxan-diabetic rats. However, acetylcholinesterase activity was significantly (P<0.05) decreased in the plasma compared with the control group, whereas, such activity did not change in brain. The activities of AST, ALT and LDH were significantly (P<0.05) decreased in the liver of alloxan-diabetic rats by 58, 21 and 40%, respectively, and such activities increased in testes by 39, 26 and 26%, respectively, compared with the control group. Also, brain LDH was significantly (P<0.05) increased. Treatment of the diabetic rats with the aqueous suspension of the tested herbs restored the activities of the above enzymes to their normal level in plasma, liver and testes. The present results showed that the herb suspensions exerted antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes. PMID- 11788162 TI - Misoprostol--for cervical ripening? PMID- 11788163 TI - Hormone replacement therapy at the threshold of 21st century. AB - The management of postmenopausal women has become a major focus for the medical profession. The menopause era should progress from a period of "chaos" to an orderly understanding of the many issues related to the menopause and hormone replacement therapy (HRT). Although HRT has beneficial clinical effect and positive benefit/risk ratio, understanding of the side effects and weight gain, and, especially, a fear of cancer limit compliance. New data from long-term, controlled, prospective studies on the effects of different HRT schedules on cancer, cardiovascular disease and osteoporotic fracture risk are needed. HRT should be considered either as for prevention or for individualized care since women experience menopause as individuals, care should be taken not to make inappropriate generalizations. The priority should be the administration of appropriate medication to women with the best result in order to improve health care and quality of life. New therapeutic options will offer substantial medical advancement for the treatment of postmenopausal women. PMID- 11788164 TI - The Manchester Siamese twins case--a French ethical analysis. AB - Conjoined twins were born on 8th August 2000 in Manchester. After a 2-month period of legal fighting between their parents and the medical team, which was widely reported in the media, the twins were surgically separated on 7th November 2000. This case-report scrutinises the ethical dilemma from a fresh perspective. PMID- 11788165 TI - Perinatal and maternal outcomes of fetal macrosomia. AB - OBJECTIVE: To determine the perinatal and maternal outcome of the macrosomic infants. STUDY DESIGN: A case-control, retrospective study is performed in the Department of Gynecology and Obstetrics, Istanbul University Cerrahpasa Medical Faculty, between 1988-1992. The maternal and neonatal records of infants with birthweight of at least 4000g (n=1000) were reviewed. Another 1000 cases amongst the newborns delivered in the same period between 2500 and 3999g formed the control group. The obstetrical outcome variables of the groups including mode of delivery and the incidence of maternal and perinatal complications were compared. RESULTS: A total of 16,112 deliveries occurred during the study period. The rate of macrosomic deliveries was 6.21% and the rate of the deliveries (4500g or heavier) was 1.04%. The mean birthweight of the study group was 4272+/-239 and 3277+/-316g of the control group (P<0.001). While the cesarean section rate was 28.8% for the study group and it was 16.6% for the control group (P<0.001). In the study group, 17 cases of brachial plexus palsy (2.4%), 16 cases of clavicular fracture (2.3%) and one case of humeral fracture were observed (P<0.001). The rate of perinatal mortality was 0.8% in the study group. No perinatal mortality was recorded in the control group. There were 14 cases (1.4%)of asphyxia related to delivery in the study group (P<0.01). The rate of maternal complications, were significantly higher in the study group (P<0.01). CONCLUSION: The macrosomic infants are in increased risk for birth trauma and asphyxia. The risk of birth trauma for the infants weighing 4500g or more is even greater. PMID- 11788166 TI - Production of vasoactive substances by human umbilical vein endothelial cells after incubation with serum from preeclamptic patients. AB - OBJECTIVE: To determine the in vitro effect of serum from preeclamptic patients on the proliferation, viability and secretion of vasoactive substances by human umbilical vein endothelial cells (HUVEC). STUDY DESIGN: HUVEC were incubated for 24h with sera from 16 preeclamptic, 19 healthy pregnant and 8 healthy nonpregnant women. Proliferation rates were determined by cell counting and vitality by trypan blue staining. The vasoactive substances, 6-keto-prostaglandin F(1alpha), nitrite and nitrate, and endothelin-1 (ET-1) were measured in endothelial cell supernatants. RESULTS: The preeclamptic serum had no effect on cell proliferation or vitality compared with control sera. It induced more HUVEC production of ET-1, but not of prostacyclin (PGI2) or nitric oxide compared with control serum. CONCLUSION: Preeclamptic serum appears to contain a factor(s) that specifically stimulates ET-1 secretion from HUVEC without altering cell growth or vitality. PMID- 11788167 TI - Gustatory and olfactory function in the first trimester of pregnancy. AB - OBJECTIVE: To investigate gustatory and olfactory sensitivity in the first trimester of pregnancy using validated test kits. DESIGN: Prospective study. SETTING: Department of Obstetrics, University Hospital Zurich, Switzerland. POPULATION: Total 53 pregnant women and 59 controls in a known phase of the menstrual cycle. METHOD: Gustatory sensitivity was assessed by requiring subjects to discriminate between four basic-taste tablets ('sweet', 'salty', 'sour', and 'bitter'). Olfactory testing was performed using the 'Sniffin' sticks' kit. Subjects rated the intensity and hedonic tone of the four tastants and of 10 common odors. RESULTS: Pregnant women had significantly lower overall gustatory sensitivity scores. There were no differences in olfactory sensitivity. However, pregnant women rated the odors 'rum', 'cigarette' and 'coffee' as more aversive than did non-pregnant women. CONCLUSION: Our data do not support the hypothesis of a generalized increase in chemosensitivity in early pregnancy. In terms of adaptive changes of the olfactory system may act as a sentinel to potentially harmful chemicals. In contrast, the gustatory system appears to retreat to allow a greater intake of electrolytes and a more widely sourced diet. PMID- 11788168 TI - Hemoglobin concentration in multiple versus singleton pregnancies--retrospective evidence for physiology not pathology. AB - OBJECTIVE: To describe hemoglobin (Hb) levels and percentiles for multiple pregnancies and to compare them with reference ranges of singleton pregnancies as published by the Center for Disease Control. STUDY DESIGN: Maternal hemoglobin and red cell indices were compared: (a) between multiple and singleton pregnancies of our hospital and (b) with trimester-specific cut-offs for singleton pregnancies obtained from literature. RESULTS: While early pregnancy hemoglobin values were similar in multiple and singleton pregnancies, second trimester values decreased much faster in multiple pregnancies. Nadir in multiple pregnancies was reached in weeks 24-28 of gestation. In the third trimester mean hemoglobin values were higher in multiple pregnancies, while 5th and 10th percentile were still lower compared to singleton pregnancies at term. The mean whole-pregnancy hemoglobin exceeded the Center for Disease Control (CDC) cut-off for anemia in singleton pregnancies (fifth percentile) and red cell indices remained constant. CONCLUSION: We conclude that with a significantly lower fifth percentile than introduced by the CDC in all trimesters, there should be different cut-offs for anemia in multiple pregnancies considered. A more pronounced decrease in multiple pregnancy hemoglobin levels seems to be physiological. PMID- 11788169 TI - Could a combined administration of dexamethasone and 3,5-dimethyl-3'-isopropyl-L thyronine (DIMIT) be a more effective alternative to dexamethasone alone in the prevention of RDS? AB - OBJECTIVE: To test whether the combined application of dexamethasone (DEXA) and 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) induces the synthesis of surfactant protein A (SP-A) mRNA at a higher rate than both substances given alone? STUDY DESIGN: Organoid culture of fetal rat lungs (Wistar rats; day 19 of gestation) was prepared. After 48h of incubation we added DEXA (10(-5), 10(-7), 10(-8) and 10(-9)mol/l), DIMIT (10(-5), 10(-7) and 10(-9)mol/l) and the combination of DEXA in 10(-8)mol/l with various concentrations of DIMIT. After another 48h of incubation, northern blot and hybridization with a 32P-labeled SP-A cDNA probe was performed. One-way-variance-analysis with a Scheffe-test, Levene-test and one sample-t-test were used for statistical analysis. RESULTS: DEXA alone above 10( 8)mol/l resulted in a significant increase, DIMIT resulted in a decrease of SP-A mRNA induction. Combined application of DIMIT and DEXA resulted in a significant increase compared to the controls. Compared to DEXA alone in 10(-8)mol/l, we found an increased induction, but the data were not significant. CONCLUSIONS: The combined application of DEXA and DIMIT shows a higher induction of SP-A mRNA than both drugs given alone. PMID- 11788170 TI - Labor pain in relation to fetal weight in primiparae. AB - AIM OF STUDY: To investigate the association between fetal weight and the experience of labor pain in primiparae. METHODS: All primiparae who gave birth at the department of obstetrics, Herning Central Hospital, from 1 September 1998 to 30 April 1999 completed a visual analogue scale (VAS) on the second day after delivery. Pain was scored in the first, the second, and the "repair" stage of labor, respectively, and finally a score was performed for total labor evaluation. RESULTS: 139 primiparae were included. Mean age was 27 years (range 16-40 years), mean fetal weight was 3562g (range 2400-5050g). There was no relationship between fetal weight and pain score. Neither was there any relationship between pain score and maternal age, body mass index (BMI), duration of second stage of labor or the need for instrumental delivery. The score in the stage of perineal repair was significantly lower than in the other stages of labor. CONCLUSION: The experienced pain during labor among primiparae is not influenced by fetal weight. PMID- 11788171 TI - A training model for external cephalic version. AB - The Royal College of Obstetricians and Gynaecologists (RCOG) has recommended that all women with an uncomplicated pregnancy and a breech presentation at term should be offered external cephalic version (ECV) but only 43% of consultants in England practice ECV. There is a need to train clinicians to perform ECV safely and effectively. A model abdomen is described which fulfils these requirements. The model is adjustable to represent a continuum from an easy procedure to an impossible procedure. The model was used to train and assess two midwives in the technique of ECV. This model is a valuable method of both training a clinician to perform ECV and also providing an objective method of assessing their technique. It has the potential to maximise the success rate of the newly trained clinician prior to performing ECV on women. PMID- 11788172 TI - The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia. AB - OBJECTIVE: This study was designed to determine the effect of garlic tablet (Garlet) on plasma lipids, and platelet aggregation and the efficacy of this treatment in the prevention of preeclampsia. STUDY DESIGN: In a randomized, single-blind, placebo-controlled study, 100 primigravidas with positive roll-over test were treated with daily doses of 800mg Garlet/day (n=50) or 800mg/day placebo (n=50) during the third trimester of pregnancy. Serum total cholesterol, LDL-and HDL-cholesterol, triglyceride, and platelet aggregation were measured before and after the treatment. Blood pressure, weight, and edema were also examined during the entire study period. RESULTS: In the case group, there was no significant difference in the means of total cholesterol, HDL, LDL, and triglyceride before and after the experiment. Furthermore, the inhibition of platelet aggregation did not show any significant difference before and after the treatment. There were not any significant difference in the means of HDL, LDL, triglyceride, inhibition of platelet aggregation, the means of systolic and diastolic blood pressure and the mean arterial blood pressure (MAP), between the two groups, but there was a significant difference in the means of total cholesterol (P=0.038) and hypertension alone (P=0.043). CONCLUSION: The administration of 800mg/day of Garlet during the third trimester of pregnancy was effective in reducing the occurrence of hypertension alone, but it was no effective in preventing of preeclampsia. PMID- 11788173 TI - Perinatal risk factors for adverse neurodevelopmental outcome after spontaneous preterm birth. AB - OBJECTIVE: The aim of this study was to investigate to what extend perinatal factors contribute to the neurodevelopmental outcome in a group neonates born after spontaneous preterm labour with or without prolonged rupture of the membranes (PROM). METHODS: In a cohort of neonates born after the spontaneous onset of labour with or without PROM before 34 weeks of gestation a stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on adverse outcome. Adverse neurodevelopmental outcome was defined as a Griffith's developmental score <85, cerebral palsy, a major disability or perinatal death associated with severe cerebral damage. RESULTS: The study group consisted of 185 neonates. Seven neonates died with severe cerebral damage. After a forward logistic regression analysis three factors appeared to have an independent influence: gestational age protected against an adverse outcome (odds ratio (OR) per day increase 0.95, 95% confidence interval (CI) 0.90-0.97) while abnormal cranial ultrasound (intraventricular haemorrhage and periventricular leucomalacia) (OR 6.33, 95% CI 2.16-18.52) and the need for a second course of antibiotics (OR 1.85, 95% CI 1.02-3.33) increased the risk for adverse outcome. Comparing the group with a normal neurodevelopmental outcome with those with cerebral palsy, cranial ultrasound abnormalities were independently associated with cerebral palsy (OR 48.75, 95% CI 11.78-201.76). CONCLUSION: The most important way of preventing neurological damage in infants is to increase gestational age at birth and to avoid the development of intraventricular haemorrhage and periventricular leucomalacia. PMID- 11788174 TI - Neutrophil oxygen radical production in pre-eclampsia with HELLP syndrome. AB - OBJECTIVE: To determine whether severe pre-eclampsia complicated by hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome alters neutrophil oxygen radical production. MATERIALS AND METHODS: Neutrophils were obtained from 10 healthy non-pregnant, 9 normal pregnant and 9 women with severe pre-eclampsia with concurrently HELLP syndrome. Oxygen radical production was evaluated using luminol-enhanced chemiluminescence and measured by cytochrome C reduction. Furthermore we incubated sera from cases and controls with isolated healthy neutrophils and measured their capacity to generate oxygen radicals. RESULTS: Unstimulated neutrophil oxygen radical production was significantly lower in severe pre-eclamptics compared with healthy non-pregnant and pregnant subjects, whereas phorbol ester-induced oxygen radical production did not differ among categories. Cytochrome C reduction of unstimulated neutrophils showed similar results. Healthy neutrophils incubated with sera from pre-eclamptics enhanced the oxygen radical production significantly more than neutrophils incubated with sera from the healthy subjects. CONCLUSIONS: Severe pre-eclampsia is characterised by decreased unstimulated neutrophil oxygen radical production. This may be the result of an exhausted cellular response due to stimulation by a factor present in the serum of these patients. PMID- 11788175 TI - The changes in ovarian hormone levels and ovarian artery blood flow rate after laparoscopic tubal sterilization. AB - OBJECTIVE: To investigate the changes in serum ovarian hormone levels and ovarian artery blood flow rate by Doppler ultrasonography following laparoscopic tubal sterilization. METHODS: Laparoscopic tubal sterilization have been performed on 13 voluntary subjects between the sixth and eighth days of the menstrual cycle. Serum ovarian hormone levels and ovarian artery blood flow rate, by Doppler ultrasonography, were determined 3 days before the operation, on the post operative third day and on the post-operative third month. The results of 10 participants who finished the follow-up period were analyzed. RESULTS: There were no statistically significant changes in serum levels of ovarian hormones after laparoscopic tubal ligation. The end-diastolic blood flow in ovarian artery was found to be decreased following tubal sterilization (8.7+/-2.8 and 7.4+/ 1.8m/sec, respectively, P>0.05), while resistivity index (RI) increased after the operation (0.7+/-0.1 and 0.8+/-0.03, respectively, P>0.05). CONCLUSION: There was no change in ovarian hormone levels after laparoscopic tubal sterilization. There is slight but statistically non-significant decrease in ovarian artery blood flow rate following tubal sterilization, signifying a local increase in vascular resistance. PMID- 11788176 TI - Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels. AB - OBJECTIVE: To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN: Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2) -0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS: Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION: Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women. PMID- 11788177 TI - Elevated interleukin-10 and sex steroid levels in peritoneal fluid of patients with ovarian hyperstimulation syndrome. AB - BACKGROUND: The ovarian hyperstimulation syndrome (OHSS) following ovulation induction is characterized by a cystic enlargement of the ovaries with an acute third space fluid sequestration. Inflammatory cytokines mediate the inflammatory response (IL-1, IL-2, IL-6, IL-8, TNFalpha) and play a crucial role in the pathogenesis of OHSS. OBJECTIVE: To determine the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in OHSS and to examine its correlation with 17beta-estradiol and progesterone. STUDY DESIGN: Peritoneal fluid and serum samples were collected from 9 patients with severe OHSS after ovulation induction by administration of GnRH-analogues followed by hMG (n=5) or recombinant FSH (n=4). Patients (n=19) without pathological findings at laparoscopy served as non pregnant controls and pregnant women (n=14) between 7 and 16 weeks of gestation served as positive controls. Samples were assayed for IL-10 by commercially available ELISA and for for 17beta-estradiol and progesterone by RIA. Statistical analysis was performed by non-parametric Mann-Whitney U-test and results are presented as the median and range. RESULTS: OHSS patients had significantly higher peritoneal fluid IL-10, 17beta-estradiol and progesterone levels than patients during early pregnancy and than the control group. No correlation was found between peritoneal fluid or serum IL-10 and 17beta-estradiol or progesterone in the different groups. Serum 17beta-estradiol and progesterone, but not serum IL-10 levels were elevated in OHSS and during early pregnancy. CONCLUSIONS: High concentrations of IL-10 in peritoneal fluid suggest a role of this anti-inflammatory cytokine during OHSS. 17beta-estradiol and progesterone were elevated in peritoneal fluid and serum during OHSS but no correlation with IL-10 concentrations was found. Therefore, we assume that IL-10 has a role in OHSS as a local mediator of inflammation, however, it presents different aspects of the OHSS than the sex steroids 17beta-estradiol and progesterone. PMID- 11788178 TI - Which contraceptive methods are recommended for young women with type 1 diabetes mellitus? A survey among gynaecologists in Greece. AB - BACKGROUND: Type 1 diabetes mellitus is common in Europeans. Optimal glucometabolic control at conception and during early pregnancy is necessary to reduce the risk of early miscarriage and congenital malformations. Safe and effective contraceptive methods are essential for these women in order to have a "planned pregnancy" under optimal conditions. AIM: To find out which recommendations Greek gynaecologists give to young patients with type 1 diabetes mellitus with respect to contraception. To regard the experience of Greek gynaecologists in counselling with women. To compare the Greek gynaecologists with German gynaecologists in a previously published similar survey. SUBJECTS AND METHODS: A structured questionnaire containing questions about attitude, health care and contraception in young women with type 1 diabetes was given to 400 Greek gynaecologists working in Athens. RESULTS: Only 70 (17.5%) of the Greek gynaecologists returned the questionnaire. Condoms were the preferred recommendation as contraceptive method for young women with diabetes mellitus type 1 in 64%. About 57% of the gynaecologists recommended this type of contraception as first line contraceptives for young women with diabetes type 1 who smoke. The two most important criteria for selection of a contraceptive method for Greek gynaecologists were the safety and the diabetes specific problems. The Greek gynaecologists had only limited experience in regard to counselling and treating young and adolescent women with type 1 diabetes. CONCLUSION: There was no consensus with respect to contraception among Greek gynaecologists. This is similar to our previous findings in a survey involving German gynaecologists. Practical experience in counselling and treating adolescent and young women with type 1 diabetes was limited among the gynaecologists who participated in this study. Working out proper recommendations for contraception crucial for optimal medical care for type 1 diabetic women in Europe. PMID- 11788179 TI - The effect of tranexamic acid on the quality of life of women with heavy menstrual bleeding. AB - OBJECTIVE: To investigate whether medical treatment with tranexamic acid would increase the quality of life of women with heavy menstrual bleeding. STUDY DESIGN: This open, uncontrolled usage study included 849 women diagnosed with heavy menstrual bleeding and considered eligible for tranexamic-acid treatment. The condition of the women was investigated at baseline and after the first and the third treated menstruation. Quality of life and subjectively experienced state of health were assessed with the aid of a questionnaire. Satisfaction with the treatment was registered. RESULTS: After the third menstruation, 80% of the women were satisfied with the treatment. Impairment of social activities and impairment at work were greatly reduced by the treatment. Substantial improvements were also recorded with regard to alertness, productivity, cleanliness, spirits, action radius and overall well-being. Adverse reactions to the drug used for the treatment were few and non-serious. CONCLUSIONS: Medical treatment with tranexamic acid increases quality of life for women with heavy menstrual bleeding. PMID- 11788180 TI - Low dose sulprostone for termination of second and third trimester pregnancies. AB - OBJECTIVE: The purpose of this study is to assess the effectiveness and safety of sulprostone (nalador) for labour induction in the event of foetal death or foetal malformations. STUDY DESIGN: Retrospective analysis of 284 women with intrauterine foetal death (n=137), or foetal abnormalities (n=147), who underwent labour induction with sulprostone in a continuous dose of 1microg/min intravenously. RESULTS: All but three women had a successful vaginal delivery. The median induction-expulsion interval was significantly shorter (12h) in the foetal death group compared to the foetal malformation group (25h). Two uterine ruptures were recorded, one in a woman with a uterine anomaly, and one in a woman with a previous caesarean section. There were no other complications. Gestational age had a significant influence on spontaneous expulsion of the placenta: before 24 weeks 55%, and after 24 weeks 82% spontaneous expulsion. For the chance of a neonate born with signs of life, parity was the only significant determinant. CONCLUSIONS: The use of intravenous sulprostone in a low continuous dose is both effective and safe. In addition, this study does not support former opinions that smoking and advanced maternal age are contraindications. PMID- 11788181 TI - Postoperative day 3 serum human chorionic gonadotropin decline as a predictor of persistent ectopic pregnancy after linear salpingotomy. AB - OBJECTIVE: To evaluate the ability of preoperative clinical, ultrasonographic, intraoperative findings and pre-postoperative serum human chorionic gonadotropin (hCG) levels to predict persistent ectopic pregnancy (EP). STUDY DESIGN: Retrospective cohorts study. SETTING: Tertiary care, university hospital. In all, 61 women with EP treated with laparoscopic linear salpingostomy between January 1995 and December 1999. RESULT: Out of 61 patients, 10 (9%) were diagnosed with a persistent EP. When compared with 51 (91%) successfully treated patients there were no differences in preoperative clinical and ultrasonographic findings, preoperative serum hCG levels and intraoperative findings. The postoperative decline of hCG levels were different in both groups. No case of persistent EP was found if the postoperative day 3 decline of hCG was more than 55%. CONCLUSION: Postoperative serum hCG follow-up is important after salpingotomy to prevent persistent EP. A decline of less than 55% at day 3 predicts persistent EP and may select early cases for second line methotrexate therapy. PMID- 11788182 TI - Paget's disease of the vulva: results of different conservative treatments. AB - OBJECTIVE: To evaluate three conservative treatments for vulvar Paget's disease: wide excision, laser alone, or limited surgery associated with laser. STUDY DESIGN: A retrospective analysis of 52 patients treated with wide excision (31 cases), limited surgery, and peripheral laser [Br J Obstet Gynecol 1995;102:359], or laser alone [Gynecol Oncol 1975;3:46]. RESULTS: Mean time to recurrence was 1+/-0.6 years after laser alone, 1.9+/-1.5 years after the association limited excision and peripheral laser, and 2.7+/-1 years after wide excision alone. At 1 year recurrence rates were 67% after laser alone, 33% after the association laser plus surgery, and 23% after wide excision. CONCLUSION: Conservative management preserves vulvar anatomy and function, but recurrence rates are high. PMID- 11788183 TI - Bcl-2 and Bax expression in human endometriotic and adenomyotic tissues. AB - OBJECTIVE: To determine the Bcl-2 and Bax expressions in endometriotic and adenomyotic tissues. In addition, to evaluate the Bcl-2/Bax status during the menstrual cycle in these tissues. METHODS: A total of 56 women were retrospectively recruited from a University hospital setting. A total of 25 had endometriosis and 31 adenomyosis. Tissue samples were collected during gynaecological surgery and confirmed by histology to have endometriosis or adenomyosis. Bcl-2 and Bax expressions were investigated on 56 formalin-fixed and paraffin-embedded tissue by immunohistochemical staining and electron microscopy. RESULTS: The difference of Bcl-2-positive protein between endometriosis and adenomyosis was not significant. No significant difference was found between Bcl 2 expression and the proliferative and secretory phase of the cycle in women with endometriosis, but this comparison was highly significant (P<0.001) in women with adenomyosis. The difference of Bax-positive protein between endometriosis and adenomyosis was not significant. In addition, no significant differences were found between the various phases of the cycle. We have found a stronger inverse correlation between the expression of Bcl-2 and Bax in endometriosis than in adenomyosis. CONCLUSIONS: Our results suggest that the pathogenesis of ovarian endometriosis may be different from that of adenomyosis and the persistence of Bcl-2 and Bax expressions during both phases of the cycle in ovarian endometriotic tissues may have important implications for the survival and proliferation of the ectopic endometrial tissue. PMID- 11788184 TI - Effect of continuous and sequential oral estrogen-progestogen replacement regimens on postmenopausal bone loss: a 2-year prospective study. AB - OBJECTIVE: The aim of the present study was to determine whether assignment to continuous estrogen-progestin therapy is more effective in protecting against bone loss than assignment to a sequential regimen. STUDY DESIGN: A total of 104 postmenopausal women were randomly assigned to one of two groups of treatment, Conjugated Equine Estrogens and Medroxyprogestin without interruption (continuous group) and Conjugated Equine Estrogens over 25 days with Medroxyprogestin beyond the 14th day (sequential group). Bone mineral density (BMD) was measured at inclusion, 12 and 24 months later by dual energy X-ray absorptiometry. RESULTS: among women completing the 2-year treatment period, continuous and sequential regimens yielded results significantly different from baseline values, but not significantly different from each other at the 12-month (4.2 and 4%) or 24-month visits (6.6 and 6.3%). In the intention-to-treat analysis, the results with both regimens also differed from baseline values; additionally, the continuous group showed a greater increase in BMD than the sequential group at the 12-month (3.5 and 3%) and at the 24-month visits (5.5 versus 4.6%). CONCLUSION: assignment to continuous administration seems to be more effective in increasing bone density than the sequential regimen. Thus, combined continuous estrogen therapy would seem to be the most effective regimen for those women requiring long-term hormone replacement therapy. PMID- 11788185 TI - Acute exacerbation of chronic maxillary sinusitis during therapy with nafarelin nasal spray. AB - OBJECTIVE: To describe a case of acute exacerbation of chronic bilateral maxillary sinusitis during therapy with nafarelin nasal spray for chronic pelvic pain and suspected adenomyosis uteri in a patient of 34 years. DESIGN: Case report. INTERVENTIONS: In the follicular stage of the cycle a diagnostic laparoscopy was carried out because of unexplained pelvic pain for 2 years with biopsy of the pelvic peritoneum and of the uterine fundus was done, revealing no pathology. One and a half years ago the patient already had a diagnostic laparoscopy for the same reason without pathological findings. Vaginal ultrasound showed minor signs of adenomyosis uteri (irregular structure of the myometrium with small cysts). One week after the operation, a therapy with nafarelin nasal spray was initiated in order to induce a hypoestrogenic state. Fourteen days later the therapy had to be stopped because of acute exacerbation of chronic maxillary sinusitis and Caldwell Luc operation and turbinoplastic was performed. OUTCOME: Resolution of the acute maxillary sinusitis after operative intervention and termination of the above-mentioned medication, resolution of pelvic pain after therapy with leuprolide after 4 weeks. CONCLUSIONS: To our knowledge, this is the first report of an acute exacerbation of a chronic maxillary sinusitis during the administration of nafarelin nasal spray. Gynecologists prescribing nasal sprays should ask their patients about symptoms of chronic sinusitis. Patients with a history of sinusitis should visit an ear, nose and throat (ENT) specialist before initiating therapy with nasal sprays; alternatively, drugs with a different formulation should be used for down-regulation of the ovarian function in order to avoid this complication. PMID- 11788186 TI - Primary malignant melanoma arising in a cystic necrotic ovarian teratoma. AB - Cystic ovarian teratomas are common tumours. Malignant melanoma developing in a teratoma, however, is an extremely rare diagnosis. To date, only 24 cases have been reported in the literature. A 56-year-old patient underwent laparotomy for an ovarian tumour. Histopathologic examination revealed a primary malignant melanoma within a cystic necrotic teratoma, possibly arising from uveal cells. An extraovarian primary melanoma could not been found. After 7 months of operation metastasis to the vertebral column occurred, 2 months later liver metastases were diagnosed. The patient died of the disease 14 months after initial diagnosis. PMID- 11788187 TI - Placental insufficiency and maternal death caused by advanced stage of breast cancer in third trimester. AB - We describe a case with placental, and general metastases, resulting in transient intrauterine and general hypoxia, and with additionally clinical features similar to HELLP syndrome. A patient in the third trimester with dyspnea at rest developed right heart failure during c-section. During emergency thoracotomy the patient went into generalized shock and died after intense CPR. Placental insufficiency was based on a multilocal metastatic event, decreasing the utero placental perfusion. PMID- 11788188 TI - Prolapsed cord after external cephalic version in a patient with premature rupture of membranes and transverse lie. AB - A 29-year-old G6 P3023 woman presented at 37 weeks' gestation with rupture of membranes and oligohydramnios. After informed consent was obtained, a successful external cephalic version (ECV) was performed. The patient went into spontaneous labor, but about 2h after the ECV, the umbilical cord prolapsed, necessitating cesarean section. Umbilical cord prolapse is a possible complication of ECV in patients with rupture of membranes and oligohydramnios. PMID- 11788189 TI - Placenta previa of a succenturiate lobe: a report of two cases. AB - Previa of a succenturiate placenta is a rare condition. We report two cases of such lesions, which could not be detected by transabdominal ultrasound. When no cause of uterine bleeding is detected, previa of a posterior succenturiate lobe should be considered, and transvaginal ultrasound should be performed. PMID- 11788190 TI - Giant uterine leiomyoma devascularized by embolization prior to surgical removal. AB - A 49-year-old woman presented a tumor of pelvic origin filling almost the whole abdominal cavity. Angiography confirmed that it arose from the uterus. Bilateral internal iliac artery embolization was performed prior to surgical removal. It was found to be a 25kg uterine leiomyoma. PMID- 11788192 TI - Specialist life--Hans Ludwig. Interview by J. G. Thornton. PMID- 11788194 TI - Localization and expression of usherin: a novel basement membrane protein defective in people with Usher's syndrome type IIa. AB - People with Usher's syndrome type IIa have mutations in a novel gene encoding a protein with domains commonly found in many types of extracellular matrix and cell surface receptor proteins. Here we report that this protein, which we refer to as usherin, is a new basement membrane protein. In the mouse, usherin has a broad, but not ubiquitous, tissue distribution. Usherin is found in all of the capillary and structural basement membranes of the human and mouse retina and in the murine inner ear at both post-natal day 0 and in the adult. High levels of usherin are also observed in tissues not affected in Usher's syndrome type IIa, including spleen, testis, oviduct, epididymis, submaxillary gland, and large and small intestines. Many organs are completely devoid of usherin, including the brain, skin, kidney, lung, liver, and skeletal muscle. Expression was observed in the smooth muscle of the small intestine, colon, and oviduct, however, usherin is not present in cardiac smooth muscle. Usherin is critical for normal development and tissue homeostasis in the inner ear and retina, illustrating yet another example of the importance of basement membranes in the development and function of tissues. PMID- 11788195 TI - Auditory brain stem responses evoked by lateralized clicks: is lateralization extracted in the human brain stem? AB - The dependence of binaurally evoked auditory brain stem responses and the binaural difference potential on simultaneously presented interaural time and level differences is investigated in order to assess the representation of stimulus lateralization in the brain stem. Auditory brain stem responses to binaural click stimuli with all combinations of three interaural time and three interaural level differences were recorded from 12 subjects and 4 channels. The latency of Jewett wave V is shortest for zero interaural time difference and longest for the trading stimuli. The amplitude of wave V is largest for centrally perceived stimuli, i.e., the diotic and trading stimuli, and smallest for the most laterally perceived stimuli. The latency of the most prominent peak of the binaural difference potential DN1 mainly depends on the interaural time difference. The amplitude of the components of the binaural difference potential, DP1-DN1, depends similarly on stimulus conditions as wave V amplitude in the case of the binaural stimuli: smallest amplitudes are found for the most lateral stimuli and largest amplitudes for central stimuli. The results demonstrate that interaural level and time differences are not processed independently. This supports the hypothesis that directional information in humans is already extracted and represented at the level of the brain stem. PMID- 11788196 TI - Strial marginal cells play a role in basement membrane homeostasis: in vitro and in vivo evidence. AB - The interaction of extracellular matrix and receptors plays a role in tissue homeostasis. The thickened strial capillary basement membrane (SCBM) reported in animal models of presbycusis and Alport's syndrome might be secondary to elevated synthesis and/or decreased turnover of specific basement membrane (BM) components. In this study, expression of specific BM proteins, integrin receptors and mediators of matrix turnover in the murine lateral wall were determined using cDNA probes and antibodies. The presence of collagen alpha1 and alpha2(IV) and laminin-8 in the SCBM was verified. The integrin subunits alpha3, alphav and beta1, cell surface receptors for the BM proteins, localized primarily to the SCBM and/or the strial marginal cells as did TIMP-3, a tissue inhibitor of matrix metalloproteinase. The epithelial cell line SV-k1, derived from the lateral wall of the 'immortomouse', showed expression of the same BM proteins as well as demonstrating the presence of markers specific to strial marginal cells, namely Na,K-ATPase alpha1 and beta2 subunits. Thus, the cultured cells are identified as deriving from marginal cells of the stria vascularis. Moreover, these data suggest that a culture system using this marginal cell line will be useful to delineate mechanisms underlying the pathologic accumulation of extracellular matrix in the SCBM. PMID- 11788197 TI - Cortical and subcortical activation with monaural monosyllabic stimulation by functional MRI. AB - Few reports have characterized auditory processing in monaural stimulation, which is important to the understanding of auditory brain activity in subjects with hearing loss. We therefore measured regional brain activity in response to monaural stimulation of 95 dB SPL monosyllables using functional magnetic resonance imaging (fMRI) in subjects with normal hearing and five with unilateral deafness as controls for 'cross-hearing'. Images were analyzed by statistical parametric mapping software. In subjects without hearing loss, the stimuli elicited cortical activation in the primary auditory (BA 41) and auditory association regions (BA 42, 22), particularly contralaterally where extent of activation was approximately 2.5 times the ipsilateral extent. All patients with profound unilateral deafness showed no statistically apparent response in the primary auditory and auditory association regions, ruling out an important influence from cross-hearing. We found fMRI to be a useful technique for analysis of auditory processing that should be applicable to patients with various hearing abnormalities. PMID- 11788198 TI - Bilateral superior cervical sympathectomy and noise-induced, permanent threshold shift in guinea pigs. AB - The rich sympathetic innervation to the cochlea suggests its potential control of cochlear blood flow and activity during noise exposure, as part of the general and local stress sympathetic reaction evoked by noise. In a previous study, superior cervical sympathectomy prior to sound exposure in guinea pigs in an awake state, resulted in reduced temporary threshold shift. The present study was conducted to explore whether this potential protection would also be manifested in conditions producing permanent threshold shift (PTS). Thirty-six guinea pigs, divided into four groups of nine guinea pigs each, were sound exposed for 2 h in an awake state. Eighteen guinea pigs underwent superior cervical sympathectomy prior to sound exposure. Auditory brainstem thresholds were recorded prior to sound exposure, and then at 24 h, 1 and 6 weeks post-exposure. Results indicated a reduced PTS at 122 dB sound pressure level (SPL) exposure, suggesting a protective effect of the sympathectomy. However, at 125 dB SPL exposure, the protective effect was reduced. PMID- 11788199 TI - Effects of age on the distortion product otoacoustic emission growth functions. AB - Age-related hearing loss (presbycusis) is thought to result from age-related degeneration (aging) of the cochlea plus the cumulative effects of extrinsic damage (noise and other ototoxic agents) and intrinsic disorders (e.g. systemic diseases). Previous studies have implicated dysfunction of the hair cells (sensory presbycusis) as the principal mechanism of age-related hearing loss. However, recent evidence from quiet-reared gerbils suggests that cochlear aging results primarily from atrophy of the stria vascularis, which is associated with diminished endocochlear potential (EP), spiral ganglion atrophy, and a relatively flat audiometric loss, termed metabolic presbycusis. Because it is not currently possible to measure EP directly in the clinical setting, we wondered if cochlear metabolic dysfunction might be evidenced indirectly from existing clinical tests, specifically, the input-output (IO) growth function of the distortion product (DP) otoacoustic emissions in relation to behavioral hearing threshold levels (HTL). We anticipated finding discordance between the IO functions and HTL with either a greater decline with age in HTL than in IO functions if an age-related metabolic dysfunction of the cochlea was operant, or a greater loss of IO function than HTL if outer hair cell dysfunction was the dominant pathology. To address this supposition we analyzed existing auditory data from a large cohort of adults to determine the change with age in three aspects of the DP IO function: area under the curve, threshold, and slope. The analyses demonstrated a greater effect of age on HTL than on the DP IO measures. This effect supports the hypothesis that strial dysfunction is a substantive factor in cochlear aging. The etiology and mechanisms for this dysfunction are conjectural at present. PMID- 11788200 TI - Constitutive expression of Hsp27 in the rat cochlea. AB - Heat shock protein-27 (Hsp27) is known to function as both a stress-inducible molecular chaperone and regulator of actin polymerization. For many cells in the cochlea, actin is part of the cytoskeleton and plays an important role in the maintenance of cochlear function. To understand the molecular processes by which the cochlear actin cytoskeleton is maintained and regulated during normal auditory function, we examined the expression and localization of Hsp27 in the normal rat cochlea. Reverse transcription-polymerase chain reaction and Western blot showed constitutive expression of Hsp27 in the normal rat cochlea. Immunofluorescence microscopy showed Hsp27-like staining is localized to the cuticular plate and lateral wall of outer hair cells. Hsp27-like immunostaining is also found in tension fibroblasts, in the root cells of the spiral limbus and in Reissner's membrane. The presence of Hsp27 in the actin-rich tension fibroblasts and outer hair cells suggests a potential role in the regulation and maintenance of the actin cytoskeleton in these cells. The presence of high levels of constitutive Hsp27 may also provide a mechanism for pre-protecting these cells against environmental stressors. PMID- 11788202 TI - The precedence effect for lateralization for the mild sensory neural hearing impaired. AB - Using dichotic signals presented by headphone, stimulus onset dominance (the precedence effect for lateralization) was investigated for six sensorineural hearing-impaired subjects. Stimuli were based on 2400-Hz lowpass-filtered 5-ms noise bursts. We used the paradigm, as described by Goverts et al. (2000, Hear. Res. 148, 88-94), in which a single noise burst is divided into leading and lagging parts, with opposite lateralization cues (viz. an interaural time delay of 0.2 ms). The occurrence of onset dominance was investigated by measuring the lateral perception of the stimulus ('left' or 'right') with fixed, equal durations of leading and lagging parts, while decreasing the absolute signal level or adding a filtered white noise. The dominance of the leading part was quantified by measuring the lateral perception of the stimulus as a function of the relative duration of the leading (and thus the lagging) part. This was done at about 40 dB sensation level (SL) in quiet and in filtered white noise, at a signal-to-noise ratio resulting in a SL of about 6 dB. Results are compared to normal hearing reference data at various SLs. Hearing-impaired data show a large variance and overall a decreased precedence effect in terms of both occurrence and quantification, which cannot be explained on basis of reduced audibility. Mean performance of the hearing-impaired subjects at 40 dB in quiet was similar to normal hearing performance in masking noise at a signal-to-noise ratio of 0 dB. PMID- 11788201 TI - Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death. AB - The ototoxic action of aminoglycoside antibiotics leading to the loss of hair cells of the inner ear is well documented. However, the molecular mechanisms are poorly defined. We have previously shown that in neomycin-exposed organotypic cultures of the cochlea, the c-Jun N-terminal kinase (JNK) pathway--associated with stress, injury and apoptosis--is activated in hair cells and leads to their death. We have also shown that hair cell death can be attenuated by CEP-1347, an inhibitor of JNK signalling [Pirvola et al., J. Neurosci. 20 (2000) 43-50]. In the present study, we demonstrate that gentamicin-induced ototoxicity leads to JNK activation and apoptosis in the inner ear hair cells in vivo. We also show that systemic administration of CEP-1347 attenuates gentamicin-induced decrease of auditory sensitivity and cochlear hair cell damage. In addition, CEP-1347 treatment reduces the extent of hair cell loss in the ampullary cristae after gentamicin intoxication. Particularly, the inner hair cells of the cochlea and type I hair cells of the vestibular organs are protected. We have previously shown that also acoustic overstimulation leads to apoptosis of cochlear hair cells and that CEP-1347 can attenuate noise-induced sensory cell loss. These results suggest that activation of the JNK cascade may be a common molecular outcome of cellular stress in the inner ear sensory epithelia, and that attenuation of the lesion can be provided by inhibiting JNK activation. PMID- 11788203 TI - The effects of a connexin 26 mutation--35delG--on oto-acoustic emissions and brainstem evoked potentials: homozygotes and carriers. AB - The purpose of this study was to examine whether outer hair cells (OHCs), inner hair cells and the brainstem auditory pathway are impaired due to a mutation in a gap junction protein, connexin 26 (Cx26), 35delG. Fifty-six individuals, from a village with widespread consanguinity and profound, non-syndromic congenital deafness, due to 35delG mutation, were selected among relatives of deaf people. The individuals were either non-carriers (n=20), heterozygous (n=20) or homozygous (n=16) for the mutation. Distortion product oto-acoustic emissions (DPOAEs) and auditory brainstem evoked potentials (ABEPs) in mutation non carriers, in heterozygotes (carriers) and in subjects homozygous for the mutation were compared in addition to audiometric evaluation. Most deaf homozygotes had no DPOAEs, except some sporadic responses at 1000, 8000 and 10000 Hz. This was also observed in audiometry which showed profound hearing loss in most cases. Two cases were unique: one had moderate to severe hearing loss and the other had severe to profound hearing loss. A significant difference was found between non carriers and carriers of 35delG: non-carriers had larger DPOAE responses than heterozygotes at all frequencies. The prevalence of responses got lower with higher frequencies in both groups, but between 6000 and 10000 Hz 50-70% of the carriers had no DPOAE responses, compared to 30-60% of non-carriers. In both groups responses diminished with age, but no significant interaction was found between age and the genetic group. ABEPs among homozygotes were variable: in most homozygotes ABEPs were absent or partial (waves III, V) with prolonged latencies, but two subjects had ABEPs within normal limits, in one ear. ABEPs were normal with no differences between carriers and non-carriers. We suggest that OHC function is affected by the 35delG mutation in Cx26. In addition, the hearing of carriers of this mutation may be impaired at very high frequencies (8000-10000 Hz), which are not assessed in routine audiometry or ABEP testing. PMID- 11788204 TI - Behavioural measurement of level-dependent shifts in the vibration pattern on the basilar membrane. AB - Physiological data suggest that the travelling wave on the basilar membrane evoked by a sinusoid of fixed frequency moves towards the base with increasing level. We describe two psychoacoustic experiments that attempted to provide evidence for and quantify the extent of such a shift in humans. In experiment 1, masking patterns were measured in forward masking using a fixed 6-kHz tone presented at 65 or 85 dB sound pressure level. The threshold for detecting a brief sinusoidal signal was measured as a function of signal frequency for several time delays of the signal relative to the end of the masker. A background noise was included to reduce 'off-frequency listening'. As the signal delay was increased, the signal level at the peaks of the masking patterns decreased and the signal frequency at the peak of the patterns moved progressively towards higher frequencies. The pattern of results was consistent with the idea of a basalward shift of the travelling wave with increasing level. The estimated shift corresponds to about 0.25 octaves for a 40-dB change in level. Experiment 2 also used forward masking. The signal was a 4-kHz tone presented at 10 dB sensation level. For three fixed masker levels (65, 85 and 95 dB), we measured the duration of the gap between the masker and signal required to give 79.4% correct detection of the signal (called the 'gap threshold') as a function of masker frequency; the longer the gap threshold, the more effective is the masker. The gap threshold patterns sometimes showed two peaks. One occurred just below the signal frequency and the frequency at the peak was hardly affected by masker level. The second peak fell at a lower frequency, and this frequency tended to decrease with increasing masker level. The gap threshold patterns tended to spread markedly towards lower frequencies with increasing masker level. The shift with level provides further evidence for a basalward spread of the travelling wave with increasing level. PMID- 11788205 TI - Hair bundle motility induced by chemoreceptors in anemones. AB - Most hair bundles are essentially fixed with respect to frequency specificity. However, hair bundles in sea anemones are dynamically tuned by actin-dependent changes in length. Tuning to low frequencies is accomplished by activation of chemoreceptors to N-acetylated sugars resulting in hair bundle elongation. We report here that following sugar-induced tuning of hair bundles, membrane currents reverse polarity in hair cells during unidirectional mechanical stimulation. Reversal in polarity of currents with sugar stimulation is inhibited if hair bundle elongation is blocked by pretreatment with cytochalasin D. A re examination of morphological changes to hair bundles reveals a sugar-induced reorientation of stereocilia in addition to elongation with chemosensitization. In controls, hair bundles are noticeably twisted. With sugar stimulation stereocilia become oriented more parallel to the long axis of the hair bundle. This sugar-induced change in orientation is similarly inhibited by cytochalasin D pretreatment. Based on these results, we present a model wherein anemone hair bundle twisting serves as a built-in safety mechanism to preserve linkages likely to be subjected to potentially damaging tension during tuning. The twisted hair bundles can untwist while elongating to relieve excessive tension on extracellular linkages between stereocilia critical to mechanosensitivity. PMID- 11788206 TI - Coronary in-stent restenosis: current status and future strategies. AB - In-stent restenosis (ISR) is a novel pathobiologic process, histologically distinct from restenosis after balloon angioplasty and comprised largely of neointima formation. As percutaneous coronary intervention increasingly involves the use of stents, ISR is also becoming correspondingly more frequent. In this review, we examine the available studies of the histology and pathogenesis of ISR, with particular reference to porcine and other animal models. An overview of mechanical treatments is then provided, which includes PTCA, directional coronary atherectomy and high speed rotational atherectomy. Radiation-based therapies are discussed, including a summary of current problems associated with this modality of treatment. Finally, novel strategies for the prevention of ISR are addressed, including novel developments in stents and stent coatings, conventional drugs, nucleic acid-based drugs and gene transfer. Until recently, limited pharmacologic and mechanical treatment options have been available for both treatment and prevention of ISR. However, recent advances in gene modification and gene transfer therapies and, more particularly, in local stent-based drug delivery systems make it conceivable that the incidence of ISR will now be seriously challenged. PMID- 11788207 TI - Retiming the failing heart: principles and current clinical status of cardiac resynchronization. AB - Left or biventricular (BiV) pacing, or cardiac resynchronization therapy, was proposed nearly 10 years ago as an adjunctive treatment for patients with advanced heart failure (HF) complicated by discoordinate contraction due to intraventricular conduction delay. Since then, both short-term and a growing number of long-term clinical trials have reported on the mechanisms and short- and mid-term efficacy of this approach, with encouraging results. Therapy is implemented with novel pacing systems incorporating an endocardial lead to stimulate the lateral free wall via a cardiac vein, and often a right ventricular (RV) apex lead to provide BiV stimulation. A third atrial sensing lead monitors intrinsic rhythm and provides timing data to ensure ventricular pre-excitation. Modulation of the electronic atrial-ventricular (AV) time delay can optimize contractile synchrony, enhance the contribution of atrial systole, and reduce mitral regurgitation. Individuals with advanced HF, a wide QRS complex often with an AV time delay, and evidence of contraction dyssynchrony in viable myocardium represent the target patient group. Short-term studies reveal systolic augmentation and chamber efficiency from pacing resynchronization that can be substantial. Long-term studies reveal improved symptoms and exercise capacity, and some report reversal of chronic cardiac dilation. However, important questions regarding long-term efficacy and mortality impact, optimal mode for pacing stimulation, and role of combined pacing/cardioverter/defibrillation devices remain unresolved. Here we review pathophysiologic mechanisms, short- and long-term clinical results, and future directions of this new and promising therapy. PMID- 11788208 TI - Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. AB - OBJECTIVES: Since B-type natriuretic peptide (BNP) is secreted by the left ventricle (LV) in response to volume elevated LV pressure, we sought to assess whether a rapid assay for BNP levels could differentiate cardiac from pulmonary causes of dyspnea. BACKGROUND: Differentiating congestive heart failure (CHF) from pulmonary causes of dyspnea is very important for patients presenting to the emergency department (ED) with acute dyspnea. METHODS: B-natriuretic peptide levels were obtained in 321 patients presenting to the ED with acute dyspnea. Physicians were blinded to BNP levels and asked to give their probability of the patient having CHF and their final diagnosis. Two independent cardiologists were blinded to BNP levels and asked to review the data and evaluate which patients presented with heart failure. Patients with right heart failure from cor pulmonale were classified as having CHF. RESULTS: Patients with CHF (n = 134) had BNP levels of 758.5 +/- 798 pg/ml, significantly higher than the group of patients with a final diagnosis of pulmonary disease (n = 85) whose BNP was 61 +/ 10 pg/ml. The area under the receiver operating curve, which plots sensitivity versus specificity for BNP levels in separating cardiac from pulmonary disease, was 0.96 (p < 0.001). A breakdown of patients with pulmonary disease revealed: chronic obstructive pulmonary disease (COPD): 54 +/- 71 pg/ml (n = 42); asthma: 27 +/- 40 pg/ml (n = 11); acute bronchitis: 44 +/- 112 pg/ml (n = 14); pneumonia: 55 +/- 76 pg/ml (n = 8); tuberculosis: 93 +/- 54 pg/ml (n = 2); lung cancer: 120 +/- 120 pg/ml (n = 4); and acute pulmonary embolism: 207 +/- 272 pg/ml (n = 3). In patients with a history of lung disease but whose current complaint of dyspnea was seen as due to CHF, BNP levels were 731 +/- 764 pg/ml (n = 54). The group with a history of CHF but with a current COPD diagnosis had a BNP of 47 +/- 23 pg/ml (n = 11). CONCLUSIONS: Rapid testing of BNP in the ED should help differentiate pulmonary from cardiac etiologies of dyspnea. PMID- 11788209 TI - A standardized definition of ischemic cardiomyopathy for use in clinical research. AB - OBJECTIVES: We sought to evaluate the association between the extent of coronary artery disease (CAD) and survival in patients with symptomatic heart failure (HF) and to create the most prognostically powerful clinical definition of ischemic cardiomyopathy. BACKGROUND: An ischemic etiology of HF is known to be a predictor of adverse outcome; however, there is no uniform definition for ischemic cardiomyopathy. METHODS: We assessed the clinical history and coronary anatomy of patients with symptomatic HF and ejection fraction < or = 40% undergoing diagnostic coronary angiography between 1986 and 1999 (n = 1,921). Five classification schemes were tested to identify the most prognostically powerful method for defining the extent of CAD and to develop the best definition of ischemic cardiomyopathy for prognostic purposes. RESULTS: A more extensive CAD was independently associated with shorter survival. When the various classification schemes were compared, a modified number-of-diseased-vessels classification, in which patients with single-vessel disease and no prior history of revascularization or myocardial infarction (MI) were classified as nonischemic, provided the most prognostic power. A definition of ischemic cardiomyopathy that incorporated this definition had more prognostic power than the traditional definition. CONCLUSIONS: Angiographically diagnosed ischemic HF is associated with shorter survival than nonischemic HF. A more extensive CAD is independently associated with shorter survival, and patients with single-vessel disease and no history of MI or revascularization should be classified as nonischemic for prognostic purposes. Standardization of the definition of ischemic cardiomyopathy will be useful in the conduct and interpretation of clinical research in HF. PMID- 11788210 TI - The prevalence of treatable left ventricular systolic dysfunction in patients who present with noncardiac vascular episodes: a case-control study. AB - OBJECTIVES: We sought to determine the prevalence of treatable left ventricular (LV) systolic dysfunction (LVSD) in patients who present with their first noncardiac vascular episode. BACKGROUND: Screening for LV dysfunction in patients who present with their first stroke (cerebrovascular accident), their first transient ischemic attack (TIA) or their first manifestation of peripheral vascular disease (PVD) may represent a golden opportunity to identify treatable LV dysfunction, and so their known high incidence of sudden cardiac death may be reduced. METHODS: Participating in this study were 522 (75%) of 700 consecutive patients (302 patients with stroke, TIA or PVD and 220 age- and gender-matched control subjects). Each underwent a full clinical assessment, 12-lead electrocardiography and two-dimensional echocardiography. Left ventricular dysfunction was defined as LV ejection fraction < or = 40%. RESULTS: Seventy-two (28%) patients with vascular disease and 11 (5.5%) control subjects were found to have LVSD. Twenty-six (28%) stroke patients, 22 (26%) patients with TIA and 24 (31%) patients with PVD had LVSD. Left ventricular systolic dysfunction was symptomatic in 44% of patients and in 35% of control subjects. CONCLUSIONS: Left ventricular systolic dysfunction is five times more common among patients with stroke, TIA and PVD than among age- and gender-matched control subjects. Asymptomatic LVSD is more common than symptomatic LVSD in these patients. These findings suggest that routine screening of all patients with noncardiac vascular episodes for LVSD should now be considered. Future studies should investigate whether identifying and treating LVSD in these patients would reduce their known high rate of cardiac death. PMID- 11788211 TI - High coronary artery calcium scores pose an extremely elevated risk for hard events. AB - OBJECTIVES: We sought to assess the natural history of a cohort of asymptomatic individuals with very high (> or = 1,000) calcium scores (CSs) on a screening electron beam tomography (EBT) not submitted to further testing after the initial scan. We also compared the outcome of our prospective cohort with that of historical controls with severe abnormalities on myocardial perfusion imaging (MPI). BACKGROUND: Coronary calcium detected on EBT imaging has been shown to correlate with the total plaque burden. However, there is still controversy as to the prognostic significance of calcium, as some investigators believe that the presence of coronary calcification may stabilize the atherosclerotic plaque. METHODS: Ninety-eight asymptomatic subjects (mean age: 62 +/- 10) were followed for an average of 17 +/- 11 months (range: 4 to 36 months) after undergoing EBT screening for the occurrence of hard coronary events (HCEs), defined as myocardial infarction or coronary death. All patients had an initial CS > or = 1,000, and in none did the results of the EBT screening lead to further invasive or non-invasive testing. RESULTS: During the follow-up period, 35 patients (36%) suffered an HCE. All events were recorded in the first 28 months of follow-up. Subjects with HCEs had higher initial CSs than subjects not suffering HCEs (1,561 +/- 270 vs. 1,199 +/- 200, p < 0.001). The annualized event rate in subjects with a CS > or = 1,000 was significantly greater than that of historical controls with severe perfusion abnormalities on MPI (25% vs. 7.4%, respectively; p < 0.0001). CONCLUSIONS: A high CS (> or = 1,000) on a screening EBT in an asymptomatic person portends a very high risk of an HCE in the short term. This risk appears to be greater than the risk associated with a severe perfusion abnormality on MPI. PMID- 11788212 TI - Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina. AB - OBJECTIVES: We tested whether acute hormone therapy reduces ambulatory electrocardiographic ischemia in postmenopausal (PMP) women with unstable angina (UA). BACKGROUND: Endothelial dysfunction contributes to the pathophysiology of UA. Acute estrogen administration improves endothelial function in PMP women with coronary artery disease and increases coronary artery blood flow. METHODS: Two hundred ninety-three PMP women with UA (mean age 69.7 years), treated with standard anti-ischemic therapy, were enrolled within 24 h of symptom onset. In a double-blind fashion, subjects were randomized to receive intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days or placebo. The primary end point was the number of ambulatory electrocardiographic ischemic events over the first 48 h. Clinical events were also determined over six months of follow up. RESULTS: Electrocardiographic ischemia did not differ among the three randomized groups. The mean number of ischemic events per patient over 48 h was 0.74 for estrogen, 0.86 for estrogen plus progesterone and 0.74 for the placebo groups (p = 0.87). The percentage of patients with ischemic events and the mean duration of ischemia did not differ between hormone- and placebo-treated patients. In-hospital and six-month rates of adverse clinical events were also similar among the three randomized groups. CONCLUSIONS: Acute hormone therapy does not reduce ischemia in PMP women with UA when added to standard anti ischemic therapy. PMID- 11788213 TI - Estrogen therapy for unstable angina: another bump for the bandwagon. PMID- 11788214 TI - Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction:a possible role for left ventricular remodeling. AB - OBJECTIVES: The aim of this study was to determine the significance of peripheral monocytosis in clinical outcome after reperfused acute myocardial infarction (AMI), especially relating to post-infarct left ventricular (LV) remodeling. BACKGROUND: Peripheral monocytosis occurs two to three days after AMI, reflecting infiltration of monocytes and macrophages into the necrotic myocardium. However, the prognostic significance of peripheral monocytosis after AMI remains to be determined. METHODS: A total of 149 patients with first Q-wave AMI were studied. White blood cell (WBC) count, percentage of monocytes and serum C-reactive protein level were measured every 24 h for four days after the onset of AMI. We assessed association between peripheral monocytosis and prognosis including pump failure, LV aneurysm and long-term outcome after AMI. RESULTS: Patients with pump failure (p < 0.0001) or LV aneurysm (p = 0.005) had higher peak monocyte counts than those without these complications. Predischarge left ventriculography revealed that peak monocyte count was positively correlated with LV end-diastolic volume (p = 0.024) and negatively correlated with ejection fraction (p = 0.023). Multivariate analyses showed that peak monocyte count > or = 900/mm(3) was an independent determinant of pump failure (relative risk [RR] 9.83, p < 0.0001), LV aneurysm (RR 4.78, p = 0.046) and cardiac events (RR 6.30, p < 0.0001), including readmission for heart failure, recurrent myocardial infarction and cardiac deaths, including sudden deaths. CONCLUSIONS: Peripheral monocytosis is associated with LV dysfunction and LV aneurysm, suggesting a possible role of monocytes in the development of LV remodeling after reperfused AMI. PMID- 11788215 TI - Monocytosis and adverse left ventricular remodeling after reperfused myocardial infarction. PMID- 11788216 TI - Contribution of nicotine to acute endothelial dysfunction in long-term smokers. AB - OBJECTIVES: The aim of this study was to determine whether nicotine, a constituent of cigarette smoke, contributes to acute endothelial dysfunction after smoking one cigarette. BACKGROUND: Animal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress. METHODS: Sixteen healthy smokers were entered into a randomized, observer-blinded crossover study comparing the effects of nicotine nasal spray (1-mg nicotine) and cigarette smoke (1-mg nicotine, 12 mg tar) on vascular reactivity in the brachial artery. Using high-resolution ultrasound, flow-mediated dilation (FMD) and endothelium-independent, nitroglycerin-induced dilation were assessed at baseline and 20 min after the administration of nicotine (spray or cigarette). RESULTS: In response to similar increases in nicotine serum levels, FMD values declined from 10.2 +/- 4.4% to 6.7 +/- 4.0% after the spray (mean difference: -3.6 +/- 2.0%, 95% confidence interval: -4.6; 2.5, p < 0.0001) and from 9.4 +/- 3.8% to 4.3 +/- 2.8% after the cigarette (-5.1 +/- 2.6%, -6.5; -3.7, p < 0.0001). Nitroglycerin-induced dilation remained similar within both periods. Performing a period effect analysis of variance, a significant influence on FMD was found for the mode of administration (p = 0.017) and the baseline value (p = 0.021). The effect on FMD was more pronounced after the cigarette than after the spray (estimated average effect difference: 1.9% FMD). Oxidation parameters did not increase significantly after nicotine spray or tobacco exposure. CONCLUSIONS: These results demonstrate that nicotine alone causes acute endothelial dysfunction, although to a lesser extent than smoking a cigarette of the same nicotine yield. However, the precise mechanisms by which nicotine leads to this altered vascular reactivity remain unclear. PMID- 11788217 TI - Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. AB - Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology. PMID- 11788218 TI - Percutaneous coronary intervention versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: The VA AWESOME multicenter registry: comparison with the randomized clinical trial. AB - OBJECTIVES: This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND: The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS: Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS: The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS: Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients. PMID- 11788219 TI - Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation. AB - OBJECTIVES: The study was done to investigate the relationship between clinical restenosis and the relative angiographic location of the recurrent restenotic lesion, after treatment of in-stent restenosis with vascular brachytherapy in the Washington Radiation for In-Stent Restenosis Trial (WRIST). BACKGROUND: Intracoronary radiation therapy reduces recurrence of in-stent restenosis. We investigated the above objective in patients enrolled in WRIST. METHODS: The WRIST study randomized 130 patients to double-blinded therapy with gamma irradiation (iridium-192 [(192)Ir]) versus placebo after interventional treatment of diffuse in-stent restenosis. After the intervention and at follow-up, three vessel segments were individually analyzed with quantitative coronary angiography: 1) the "stent," 2) the "radiation ribbon," and 3) the "ribbon+margin" segment (including 5 mm on either end of the injured or radiation ribbon segment). Receiver operator curves (ROC) were used to assess the value of the follow-up percent diameter stenosis (DS) for each of the three analyzed segments in predicting target vessel revascularization (TVR). RESULTS: (192)Ir reduced recurrent restenosis (23.7% vs. 60.7%, p < 0.001) and the length of recurrent restenosis (8.99 +/- 4.34 mm vs. 17.54 +/- 10.48 mm, p < 0.001) at follow-up compared to placebo. Isolated stent edge (3.4%) and ribbon edge (1.7%) restenoses were infrequent in both groups. The best angiographic surrogate of TVR was the 50% follow-up DS obtained from the ribbon+margin analysis (ROC area 0.806). CONCLUSIONS: In WRIST, not only was (192)Ir therapy effective in reducing restenosis, but it also reduced the lesion length of treatment failures by 50%, and it was not associated with edge proliferation. The restenosis rate obtained from the vessel segment inclusive of the dose fall-off zones was the best correlate of TVR and should become a standard analysis site in all vascular brachytherapy trials. PMID- 11788220 TI - Local intracoronary administration of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis: results of the randomized investigation by the Thoraxcenter of antisense DNA using local delivery and IVUS after coronary stenting (ITALICS) trial. AB - OBJECTIVE: This study was designed to determine whether antisense oligodeoxynucleotides (ODN) directed against the nuclear proto-oncogene c-myc could inhibit restenosis when given by local delivery immediately after coronary stent implantation. BACKGROUND: Failure of conventional pharmacologic therapies to reduce the incidence of coronary restenosis after percutaneous revascularization techniques has prompted interest in the use of agents that target intracellular central regulatory mechanisms. METHODS: Eighty-five patients were randomly assigned to receive either 10 mg of phosphorothioate-modified 15 mer antisense ODN or saline vehicle by intracoronary local delivery after coronary stent implantation. The primary end point was percent neointimal volume obstruction measured by computerized analysis of electrocardiogram-gated intravascular ultrasound (IVUS) at six-month follow-up. Secondary end points included clinical outcome and quantitative coronary angiography analysis. RESULTS: Analysis of follow-up IVUS data was performed on 77 patients. In-stent volume obstruction was similar between groups (44 +/- 16% and 46 +/- 14%, placebo vs. ODN; p = 0.57; 95% confidence interval: -1.13 to 0.85). Minimum luminal diameter increased from 0.84 +/- 0.36 and 0.90 +/- 0.45 (p = 0.55) to 2.70 +/- 0.37 and 2.80 +/- 0.37 (p = 0.28) after stent implantation, which decreased to 1.50 +/- 0.61 and 1.50 +/- 0.53 (p = 0.98) by six months, yielding similar loss indexes (placebo vs. ODN, respectively). There were no differences in angiographic restenosis rates (38.5 and 34.2%; p = 0.81; placebo vs. ODN) or clinical outcome. CONCLUSIONS: Treatment with 10 mg of phosphorothioate-modified ODN directed against c-myc does not reduce neointimal volume obstruction or the angiographic restenosis rate in this patient population. PMID- 11788221 TI - Plasma atrial natriuretic peptide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation: plasma ANP as a possible biochemical marker to predict the outcome of the maze procedure. AB - OBJECTIVES: We hypothesized that the plasma atrial natriuretic peptide (ANP) level reflects atrial degenerative change and may predict the outcome of the maze procedure. BACKGROUND: Although a larger preoperative left atrial dimension and longer duration of atrial fibrillation (AF) have been reported in patients with persistent AF than in those with sinus rhythm (SR), these individual factors were not enough to predict the outcome of the maze procedure. METHODS: Preoperative plasma ANP levels were measured in consecutive 62 patients who underwent the Kosakai's modified maze procedure. Moreover, we performed histological and molecular biological examinations in the resected left atrial tissues. RESULTS: The preoperative plasma ANP was lower in the AF group (n = 13) than it was in the SR group (n = 49) (p < 0.001). Multiple logistic regression analysis revealed that duration of AF and plasma ANP were independently associated with postoperative cardiac rhythm. Among 41 patients with a higher plasma ANP or shorter duration of AF than the median value, SR was restored in 95% of patients. In contrast, in 21 patients with a lower plasma ANP and a longer duration of AF than the median value, SR was restored only in 48% of patients. Histological examination revealed that the collagen volume in the left atrial tissue was higher in AF than it was in SR and inversely correlated with plasma ANP. In addition, the messenger RNA expressions of ANP, collagen type I and type III were lower in AF than they were in SR. CONCLUSIONS: These results suggest that a combination of plasma ANP and/or duration of AF may predict the success rate for the maze operation. Advanced atrial degenerative change may result in a decrease of atrial ANP secretion. PMID- 11788222 TI - Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy. AB - OBJECTIVES: This study was designed to determine the prognostic value of onset heart rate (OHR) in T-wave alternans (TWA) in patients with nonischemic dilated cardiomyopathy (DCM). BACKGROUND: One of the current major issues in DCM is to prevent sudden cardiac death (SCD). However, the value of the OHR of TWA as a prognostic indicator in DCM remains to be elucidated. METHODS: We prospectively investigated 104 patients with DCM undergoing TWA testing. The end point of this study was defined as SCD, documented sustained ventricular tachycardia/ventricular fibrillation. Relations between clinical parameters and subsequent outcome were evaluated. RESULTS: Forty-six patients presenting with TWA were assigned to one of the following two subgroups according to OHR for TWA of < or = 100 beats/min: group A (n = 24) with OHR < or = 100 beats/min and group B (n = 22) with 100 < OHR < or = 110 beats/min. T-wave alternans was negative in 37 patients (group C) and indeterminate in 21 patients. The follow-up result comprised 83 patients with determined TWA. During a follow-up duration of 21 +/- 14 months, there was a total of 12 arrhythmic events, nine of which included three SCDs in group A, two in group B and one in group C. The forward stepwise multivariate Cox hazard analysis revealed that TWA with an OHR < or = 100 beats/min and left ventricular ejection fraction were independent predictors of these arrhythmic events (p = 0.0001 and p = 0.0152, respectively). CONCLUSIONS: The OHR of TWA is of additional prognostic value in DCM. PMID- 11788223 TI - Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy. AB - OBJECTIVES: We sought to assess the occurrence and clinical significance of stroke and peripheral arterial embolizations at non-central nervous system sites in a large, community-based cohort with hypertrophic cardiomyopathy (HCM). BACKGROUND: Such vascular events are insufficiently appreciated complications of HCM for which there is limited information on occurrence, clinical profile and determinants. METHODS: We assessed the clinical features of patients with stroke and other peripheral vascular events in a consecutive group of patients with HCM from four regional cohorts not subject to significant tertiary referral bias. RESULTS: Of the 900 patients, 51 (6%) patients experienced stroke or other vascular events over 7 +/- 7 years, including 44 patients with stroke; 21 (41%) of these 51 patients died or were permanently disabled. The overall incidence was 0.8%/year and 1.9% for patients >60 years old. Age at first event ranged from 29 to 86 years (mean 61 +/- 14 years). Most (n = 37; 72%) events occurred in those >50 years, although 14 (28%) younger patients (< or = 50 years) also had events. Multivariate analysis showed stroke and other peripheral vascular events to be independently associated with congestive symptoms and advanced age, as well as with atrial fibrillation (in 45 [88%] of 51 patients), at the initial evaluation. The cumulative incidence of these events among patients with atrial fibrillation was significantly higher in non-anticoagulated patients as compared with patients receiving warfarin (31% vs. 18%; p < 0.05). CONCLUSIONS: Stroke and peripheral embolizations showed a 6% prevalence rate and an incidence of 0.8%/year in a large, unselected HCM group. These profound complications of HCM, which may lead to disability and death, were substantially more common in the elderly, occurred almost exclusively in patients with paroxysmal or chronic atrial fibrillation and appeared to be reduced in frequency by anticoagulation. PMID- 11788224 TI - Impact of left ventricular outflow tract area on systolic outflow velocity in hypertrophic cardiomyopathy: a real-time three-dimensional echocardiographic study. AB - OBJECTIVES: The aim of this study was to use real-time three-dimensional echocardiography (3DE) to investigate the quantitative relation between minimal left ventricular (LV) outflow tract area (A(LVOT)) and maximal LV outflow tract (LVOT) velocity in patients with hypertrophic obstructive cardiomyopathy (HCM). BACKGROUND: In patients with HCM, LVOT velocity should change inversely with minimal A(LVOT) unless LVOT obstruction reduces the pumping capacity of the ventricle. METHODS: A total of 25 patients with HCM with systolic anterior motion (SAM) of the mitral valve leaflets underwent real-time 3DE. The smallest A(LVOT) during systole was measured using anatomically oriented two-dimensional "C planes" within the pyramidal 3DE volume. Maximal velocity across LVOT was evaluated by two-dimensional Doppler echocardiography (2DE). For comparison with 3DE A(LVOT), the SAM-septal distance was determined by 2DE. RESULTS: Real-time 3DE provided unique information about the dynamic SAM-septal relation during systole, with A(LVOT) ranging from 0.6 to 5.2 cm(2) (mean: 2.2 +/- 1.4 cm(2)). Maximal velocity (v) correlated inversely with A(LVOT) (v = 496 A(LVOT)(-0.80), r = -0.95, p < 0.001), but the exponent (-0.80) was significantly different from 1.0 (95% confidence interval: -0.67 to -0.92), indicating a significant impact of small A(LVOT) on the peak LVOT flow rate. By comparison, the best correlation between velocity and 2DE SAM-septal distance was significantly (p < 0.01) poorer at -0.83, indicating the superiority of 3DE for assessing A(LVOT). CONCLUSIONS: Three-dimensional echocardiography-measured A(LVOT) provides an assessment of HCM geometry that is superior to 2DE methods. These data indicate that the peak LVOT flow rate appears to be significantly decreased by reduced A(LVOT). Real-time 3DE is a potentially valuable clinical tool for assessing patients with HCM. PMID- 11788226 TI - Hypertensive response to exercise: a potential cause for new wall motion abnormality in the absence of coronary artery disease. AB - OBJECTIVES: We sought to characterize patients with a hypertensive response during exercise echocardiography and its effect on results of the test. BACKGROUND: A hypertensive response to exercise has been shown to cause false positive results in perfusion imaging, radionuclide angiography and exercise electrocardiography, but its influence on exercise echocardiography has not been reported. METHODS: We identified 548 of 6,686 patients who had coronary angiography within four weeks after exercise echocardiography from 1992 through 1996. Echocardiographic results from 132 patients (24%) with a hypertensive response to exercise, defined as systolic blood pressure (SBP) >220 mm Hg for men and SBP >190 mm Hg for women or as an increase in diastolic blood pressure (DBP) >10 mm Hg or DBP >90 mm Hg during exercise echocardiography, were compared with those from 416 patients without a hypertensive response. RESULTS: Of 132 patients with a hypertensive response to exercise, 108 patients had exercise echocardiographic results positive for ischemia. Of these patients, 24 (22%) were found to have no significant coronary artery disease (CAD). In contrast, of 320 patients with positive exercise echocardiographic results without a hypertensive response, 39 (12%) patients did not have significant CAD. Among the false positive results, new wall motion abnormalities were extensive in 15 of 24 (63%) hypertensive responders involving >25% of segments compared with 14 of 39 non hypertensive responders (36%, p = 0.012). CONCLUSIONS: An excessive rise in blood pressure during exercise is associated with a greater likelihood of new or worsening abnormalities with exercise, which may be observed in the absence of angiographically significant coronary artery stenosis. PMID- 11788225 TI - Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy. AB - OBJECTIVES; We present a meta-analysis based on three recent, substantial, randomized outcome trials and several smaller trials that compared calcium channel blockers (CCBs) with conventional therapy (diuretics or beta-blockers) or with angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: There is continuing uncertainty about the safety and efficacy of CCBs in the treatment of hypertension. Previous meta-analyses conflict and suggest that CCBs increase myocardial infarction (MI) or protect from stroke. METHODS: Standard procedures for meta-analysis were used to analyze three major trials on 21,611 patients and another three lesser studies to a total of 24,322 patients. RESULTS: Calcium channel blockers have a strikingly similar risk of total and cardiovascular mortality and of major cardiovascular events to conventional therapy. Calcium channel blockers give a lower risk of nonfatal stroke (-25%, p = 0.001) and a higher risk of total MI (18%, p = 0.013), chiefly nonfatal (18%). After performing the Bonferroni correction for multiplicity, these p values become 0.004 and 0.052, respectively. When compared with ACE inhibitors in 1,318 diabetic patients, CCBs had a substantially higher risk of nonfatal (relative risk [RR] = 2.259) and total MI (RR = 2.204, confidence interval 1.501 to 3.238; p = 0.001 or 0.004 with Bonferroni correction). Total and cardiovascular mortality rates are similar. To confirm the hypothesis that ACE inhibitors are superior to CCBs in diabetic patients requires more trial data, especially with renal end points. CONCLUSIONS: Mortality (total and cardiovascular) and major cardiovascular events with CCBs were apparently similar to those events seen with conventional first-line therapy (diuretics or beta-blockers). Stroke reduction more than balanced increased MI. In diabetics, CCBs may be less safe than ACE inhibitors. PMID- 11788227 TI - Serial echocardiographic evaluation of restenosis after successful percutaneous mitral commissurotomy. AB - OBJECTIVES: This study was designed to determine predictors of restenosis after successful percutaneous mitral commissurotomy (PMC) and its relationship to late clinical outcome. BACKGROUND: The restenosis rate after PMC and its relationship to late clinical outcome is poorly defined. METHODS: Serial echocardiography was performed in 310 patients who underwent PMC. Restenosis, defined as mitral valve area (MVA) <1.5 cm(2) and > or = 50% loss of initial MVA increase, was determined by both two-dimensional (2D) and Doppler echocardiography. Clinical, echocardiographic and cardiac catheterization variables were evaluated to determine predictors of restenosis. The relationship between restenosis and major adverse clinical events (death, repeat PMC or mitral valve replacement) and functional status was assessed. RESULTS: Acute procedural success occurred in 206 patients (66%), who were then followed for restenosis. The cumulative restenosis rate was approximately 40% at six years after successful PMC (44% by 2D and 40% by Doppler MVA). The only independent predictor of restenosis was echocardiographic score (restenosis at five years was 20% for score <8 vs. 61% for score > or = 8, p < 0.001). The decline in MVA and occurrence of restenosis was gradual and progressive during the follow-up period. Procedural results and baseline factors predicted event-free survival. Restenosis by 2D MVA was related to adverse events or New York Heart Association functional class 3 to 4 symptoms, but restenosis was not an independent predictor of clinical outcome by multivariate analysis. CONCLUSIONS: Restenosis is a common, gradual and progressive occurrence after successful PMC and is predicted by higher echocardiographic score. Restenosis is related to late adverse clinical outcome, though clinical outcome remains best predicted by the acute procedural results of PMC. PMID- 11788228 TI - Gadolinium-enhanced three-dimensional magnetic resonance angiography of pulmonary and systemic venous anomalies. AB - OBJECTIVE: The goal of this study was to evaluate the diagnostic value of gadolinium (Gd)-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) in patients with congenital and acquired anomalies of the pulmonary and systemic veins. BACKGROUND: Gadolinium-enhanced 3D MRA is a fast magnetic resonance imaging technique that has shown great promise in the evaluation of large and medium-sized arteries. However, its application to venous anomalies has not been studied in detail. METHODS: The study retrospectively analyzed all patients who underwent Gd-enhanced 3D MRA examination from January 1998 through January 2001, were diagnosed with anomalies of the pulmonary or systemic veins and had additional diagnostic data available for comparison with the MRA findings. RESULTS: Sixty-one patients (age 1 day to 60 years) were included. Image acquisition was completed in 29 +/- 6.9 s. Pulmonary venous anomalies were found in 37 patients, systemic venous anomalies in 17 patients and both pulmonary and systemic venous anomalies in 7 patients. Compared with available diagnostic information by other modalities, all known or suspected venous anomalies were imaged by 3D MRA. In three patients, catheterization did not detect anomalies of the pulmonary veins that were subsequently diagnosed by MRA. The 3D MRA diagnoses were followed by 10 interventional catheterization procedures and 15 operations. In 74% of patients, 3D MRA either diagnosed previously unsuspected venous anomalies (28%) or added new clinically important information (46%). The mechanism of pulmonary vein compression in eight patients was determined by MRA but not by other imaging modalities. Using a five-level grading system for MRA image quality (1 = nondiagnostic; 5 = excellent), the average grade was 4.6 +/- 0.6, with a 0.28 +/- 0.6 mean grade difference between two independent observers. CONCLUSIONS: Gadolinium-enhanced 3D MRA is capable of rapidly and accurately diagnosing a wide spectrum of pulmonary and systemic venous anomalies and is a useful noninvasive alternative to diagnostic catheterization. PMID- 11788229 TI - Isolated neonatal ductus arteriosus aneurysm. AB - OBJECTIVE: A prospective study was performed to evaluate the incidence, clinical manifestations and outcome of ductus arteriosus aneurysm (DAA) in full-term neonates. BACKGROUND: Ductus arteriosus aneurysm has been considered to be a rare congenital lesion and a potentially fatal abnormality. METHODS: A total of 548 full-term neonates received echocardiographic screening. RESULTS: There were 48 (8.8%) patients (28 boys and 20 girls) with DAA detected by echocardiography. The maximal diameter of the DAA ranged from 6.5 to 11.2 mm (8.2 +/- 1.2 mm). All cases were asymptomatic. There were no significant differences in gender, gestational age, maternal age or Apgar score between the newborns with or without DAA. Newborns with DAA had a higher birth body weight, higher incidence of maternal gestational diabetes mellitus and more mothers with blood group A, compared with newborns without DAA (p < 0.05). Follow-up echocardiograms showed spontaneous closure of the ductus arteriosus in all patients except those without DAA. The DAA became progressively smaller after ductal closure in 33 patients (70.2%) and completely disappeared by 7 to 35 days of life. The other 14 patients (29.8%) with DAA had echocardiographic evidence of progressive formation of thrombi between the third and tenth day of life. The DAA and thrombi spontaneously disappeared in all patients by one month after birth. CONCLUSIONS: There is a higher incidence of DAA with a good outcome in our series compared with previous reports. We speculate that the presence of DAA may be a normal variant of the ductal bump and part of a normal process of spontaneous ductal closure in full-term neonates. PMID- 11788230 TI - Congenital ductus arteriosus aneurysm. PMID- 11788231 TI - Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. AB - OBJECTIVES: We sought to investigate the effects of adding spironolactone (SP) to angiotensin-converting enzyme (ACE) inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF). BACKGROUND: Adding SP to ACE inhibitors reduces mortality and morbidity in CHF. Endothelial vasomotor dysfunction contributes to increased peripheral vascular resistance and reduced myocardial perfusion in CHF. METHODS: Seven days after extensive myocardial infarction (CHF) or sham operation, Wistar rats were treated with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight per day), SP (10 mg/kg per day) or a combination of both for 11 weeks. RESULTS: Maximal acetylcholine induced, nitric oxide (NO)-dependent relaxation was significantly attenuated in aortic rings from rats with CHF as compared with sham-operated animals (R(max) 44 +/- 3% vs. 63 +/- 3%). Spironolactone alone had no influence (46 +/- 5%) and TR improved NO-mediated relaxation (55 +/- 4%), whereas treatment with both completely restored endothelium-dependent vasorelaxation (64 +/- 4%). Aortic superoxide formation was significantly increased in rats with CHF as compared with sham-operated animals, but was normalized by treatment with SP or SP plus TR. In addition, aortic messenger ribonucleic acid expression of the oxidase subunit p22(phox) in rats with CHF was significantly reduced by SP or TR plus SP. Endothelial NO synthase expression was increased in TR-treated animals. Incubation of isolated porcine coronary arteries with SP dose-dependently attenuated superoxide formation. CONCLUSIONS: Spironolactone added to an ACE inhibitor normalizes NO-mediated relaxation in experimental CHF by beneficially modulating the balance of NO and superoxide anion formation. PMID- 11788232 TI - Biphasic waveform external defibrillation thresholds for spontaneous ventricular fibrillation secondary to acute ischemia. AB - OBJECTIVES: The goal of this study was to determine if the defibrillation threshold (DFT) after spontaneous ventricular fibrillation (VF) secondary to acute ischemia differs from the DFT for electrically induced VF in the absence of ischemia in anesthetized, closed-chest dogs and pigs. BACKGROUND: The efficacy of external defibrillators has been tested mainly in animals and humans using E-VF, yet external defibrillators are often used in patients to halt S-VF. METHODS: Protocol 1: biphasic truncated exponential (BTE) waveform shocks were delivered through electrodes placed in an anterior-anterior (A-A) position (left and right lateral thorax) in nine dogs. After measuring the E-VF DFT, acute ischemia was induced with an angioplasty balloon in either the left anterior descending or left circumflex coronary artery, and the S-VF DFT was determined. Protocol 2: in a group of 12 pigs, the E-VF DFT and S-VF DFT were determined for electrodes in the A-A position and in the anterior-posterior position (A-P). Protocol 3: the E VF DFT was determined in seven pigs. Then up to three shocks 1.5x the E-VF DFT were delivered to S-VF. If defibrillation did not occur, a step-up protocol was used until defibrillation occurred. RESULTS: Protocol 1: the DFT for E-VF was 65 +/- 28 J (mean +/- SD) compared with 226 +/- 97 J for S-VF, p < 0.05. Protocol 2: the DFT was 152 +/- 58 J for E-VF and 315 +/- 123 J for S-VF for A-A electrodes. The DFT was 100 +/- 43 J for E-VF and 206 +/- 114 J for S-VF for A-P electrodes. Protocol 3: 11/37 shocks of strength 1.5x E-VF DFT (182 +/- 40 J) stopped the arrhythmia. The episodes of S-VF not halted by these shocks required energy levels of up to 400 J for defibrillation. CONCLUSIONS: External defibrillation of S-VF induced by acute ischemia requires significantly more energy than VF induced by 60-Hz current in the absence of ischemia. A safety margin >1.5x the DFT for electrically induced VF may be necessary in BTE external defibrillators to defibrillate S-VF. PMID- 11788233 TI - Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes. AB - OBJECTIVES: This study was conducted to investigate the effects of thyroid hormone on the electrophysiological characteristics of pulmonary vein (PV) cardiomyocytes. BACKGROUND: Hyperthyroidism is an important etiology of paroxysmal atrial fibrillation (AF). Pulmonary veins are known to initiate paroxysmal AF. METHODS: The action potential and ionic currents were investigated in single rabbit PV and atrial cardiomyocytes with (hyperthyroid) and without (control) incubation of L-triiodothyronine using the whole-cell clamp technique. RESULTS: Compared with the control cardiomyocytes, hyperthyroid PV and atrial cardiomyocytes had shorter action potential duration. Hyperthyroid PV cardiomyocytes had faster beating rates (1.82 +/- 0.13 Hz vs. 1.03 +/- 0.15 Hz, p < 0.005) and a higher incidence of delayed after depolarization (beating: 92% vs. 6%, p < 0.0001; non-beating: 45% vs. 3%, p < 0.005). However, only hyperthyroid PV beating cardiomyocytes had a higher incidence of early after depolarization (46% vs. 0%, p < 0.0001). The ionic current experiments showed that hyperthyroid PV beating cardiomyocytes had larger densities of overall slow inward (2.72 +/- 0.21 pA/pF vs. 2.07 +/- 0.19 pA/pF, p < 0.05), overall transient outward (1.39 +/ 0.21 pA/pF vs. 0.48 +/- 0.08 pA/pF, p < 0.001) and steady state outward currents (0.78 +/- 0.06 pA/pF vs. 0.58 +/- 0.04 pA/pF, p < 0.05) on depolarization and larger transient inward (0.021 +/- 0.004 pA/pF vs. 0.005 +/- 0.001 pA/pF, p < 0.001) on repolarization. By contrast, the hyperthyroid PV non-beating cardiomyocytes had larger densities of overall transient outward (1.01 +/- 0.14 pA/pF vs. 0.37 +/- 0.07 pA/pF, p < 0.001), steady state outward (0.61 +/- 0.06 pA/pF vs. 0.44 +/- 0.04 pA/pF, p < 0.05) and transient inward currents (0.011 +/- 0.002 pA/pF vs. 0.003 +/- 0.001 pA/pF, p < 0.05). CONCLUSIONS: Thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism. PMID- 11788234 TI - President's page: teaching: today's investment in tomorrow. PMID- 11788236 TI - GSK-3 and the neurodevelopmental hypothesis of schizophrenia. AB - The Neurodevelopmental Hypothesis of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances offer insights into the regulation of brain development. The Wnt family of genes plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3beta (GSK-3beta), accumulation and activation of beta-catenin and expression of genes involved in neuronal development. Alteration in the Wnt transduction cascade, which may represent an aberrant neurodevelopment in schizophrenia, is discussed. Programmed cell death is also an essential component of normal brain development. Abnormal neuronal distribution found in schizophrenic patients' brains may imply aberrant programmed cell death. GSK-3 participates in the signal transduction cascade of apoptosis. The possible role of aberrant GSK-3 in the etiology of schizophrenia is discussed. PMID- 11788235 TI - Endogenous digitalis-like ligands of the sodium pump: possible involvement in mood control and ethanol addiction. AB - This review addresses possible involvement of endogenous digitalis-like sodium pump ligands (SPL) in the mood control and ethanol addiction. Endogenous SPL include cardenolide and bufadienolide classes. Multiple SPL and multiple isoforms of the Na/K-ATPase, one of the key membrane enzymes, comprise a complex regulatory system. In the nervous system, pattern of expression of Na/K-ATPase is based on multiple alpha/beta isoform combinations. Clinical studies demonstrate changes in the activity of Na/K-ATPase in patients with bipolar and unipolar mood disorders. The effects of ethanol on the Na/K-ATPase are concentration-dependent and are associated with both inhibition and activation of enzyme activity. Reinforcing effect of ethanol as well as its voluntary consumption may be affected by digitalis glycosides and endogenous SPL. PMID- 11788237 TI - Hair analysis for cannabinoids and amphetamines in a psychosis incidence study. AB - It remains often uncertain whether the use of illicit substances has contributed to the aetiology of psychosis. Gas chromatography-mass spectrometry can be used to detect them in hair of the head. Given a monthly growth rate between 1.0 and 1.5 cm, one can examine hair segments that originated during the pre-psychotic period. We examined the usefulness of hair analysis to detect the use of cannabinoids or amphetamines during this period. One hundred patients participated in a psychosis incidence study and 64 yielded hair. Refusal was associated with non-Dutch ethnicity, not with a clinical diagnosis of use. A monthly growth rate of 1.5 cm was assumed and 33 specimens were found to be long enough. Cannabinoids or amphetamines were detected in nine specimens. In seven they were not detected, whereas the patients had reported their use. It is likely that their hair grew at a slower rate and that the examined segments belonged to an earlier period of time, during which the substances were not used. Lack of knowledge about the individual hair growth rate is an important limitation to the usefulness of this method. PMID- 11788238 TI - The impact of side-effects of antipsychotic agents on life satisfaction of schizophrenia patients: a naturalistic study. AB - This study compared the impact of side-effects of antipsychotic treatment, clinical and psychosocial factors on the subjective quality of life (QOL) of hospitalized patients. We surveyed 161 patients meeting DSM-IV criteria for schizophrenia stabilized on conventional and atypical antipsychotic drugs using standardized measures of adverse events, psychopathology, psychosocial variables, and perceived QOL. We found that patients with adverse events reported less satisfaction with life domains of subjective feelings and general activities than asymptomatic patients. Patients treated with conventional and novel antipsychotic agents had comparable QOL ratings. Multiple regression analysis showed total variance in QOL ratings as follows: psychosocial factors, 20.9%; clinical symptoms and associated distress, 10.1%; adverse effects, 3.2%. Thus, medication side-effects influence subjective quality of life of schizophrenia inpatients significantly less than other clinical and psychosocial factors. Patient's subjective response to these events rather than their number is more predictive of QOL. PMID- 11788239 TI - Effects of yohimbine and apomorphine on the male sexual behaviour pattern of the golden hamster (Mesocricetus auratus). AB - It has been reported that the copulatory pattern of male hamsters differs from that displayed by most rodents. Besides mount, intromission and ejaculatory patterns, male hamsters display a peculiar copulatory pattern known as long intromission (LI). This peculiar behavioural pattern emerges after the male has been allowed to ejaculate repeatedly. Although LIs have been linked to sexual exhaustion, their functional meaning and their pharmacological regulation have not yet been elucidated. In this study, the sexual behaviour pattern of male golden hamsters was analysed after the administration of yohimbine and apomorphine, drugs that selectively acts on the noradrenergic and dopaminergic system, respectively. Both drugs have proved effective in inducing facilitation of masculine sexual behaviour in several species, including rodents. Results showed that, as in rats, the administration of yohimbine and apomorphine in male hamsters seems to have a stimulatory effect on masculine sexual behaviour, although their effects differ in characteristics and in intensity. In particular, after yohimbine administration, the onset of LIs appears sooner than in control subjects and it seems that they are linked to the number of ejaculations. In addition, sexual activity seems increased after the onset of LIs, including an increase in ejaculations and in the number of LIs. On the other hand, apomorphine administration induced just a slight stimulatory effect limited to ejaculatory latency and postejaculatory interval. Concerning LIs, apomorphine induced a complete disappearance of LIs in 60% of the subjects. The full significance of these findings remains to be elucidated. PMID- 11788240 TI - Increased REM sleep after intra-dorsal raphe nucleus injection of flesinoxan or 8 OHDPAT: prevention with WAY 100635. AB - The effects of 8-OHDPAT and flesinoxan, two selective 5-HT(1A) receptor agonists, and of WAY 100635, a selective 5-HT(1A) receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The serotonergic ligands were microinjected directly into the dorsal raphe nucleus (DRN). Direct administration of flesinoxan (25.0-50.0 ng) into the DRN induced a significant increment of REM sleep (REMS) during the second and third 2 h of recording. Microinjection of 8-OHDPAT (50.0 ng) induced similar effects on REMS during the second 2 h of recording. On the other hand, intra-DRN injection of WAY 100635 (12.5-50.0 ng) significantly reduced REMS during the second 2 h recording period. REM sleep values had also decreased significantly during the first 2 h of recording after the 50 ng dose. Pretreatment with WAY 100635 (25.0 or 50.0 ng) prevented the increase of REMS induced by flesinoxan (25.0 ng) during the second two recording hours. Our findings support the proposal that activation of somatodendritic 5-HT(1A) receptors in the DRN increases REMS, whereas their blockade induces the opposite effect. PMID- 11788241 TI - Intravenous mirtazapine in the treatment of depressed inpatients. AB - Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients. PMID- 11788242 TI - The impact of smoking and drinking on plasma levels of norharman. AB - The hypothesized role of the beta-carboline norharman in processes of drug dependence forms the basis for several studies on plasma levels of norharman among substance-using populations, particularly among alcoholics and smokers. However, it is not clear whether norharman is implicated in processes of dependence to both substances, or only to tobacco smoke. In the present study plasma concentrations of norharman were measured among four groups of participants regarding heavy smokers who do or do not drink alcohol excessively and nonsmokers who do or do not drink alcohol excessively. All measurements were conducted on three different days with an interval of 2 months in between and at three times during the day to account for possible circadian or seasonal variations. Results showed that elevated plasma levels of norharman appear only in heavy smokers regardless of their drinking profile. The norharman plasma levels of nonsmoking excessive drinkers showed a similar pattern to that of the control group. The findings indicate that elevated plasma levels of norharman are due to heavy smoking and not to excessive drinking. PMID- 11788243 TI - Serotonin transporter promoter genotype and illness recurrence in mood disorders. AB - We tested the hypothesis that allelic variation of 5-HTT linked polymorphic region (5-HTTLPR) could influence illness onset and recurrence in 129 bipolar and 128 unipolar recurrent patients. Among bipolar patients, homozygotes for the short variant showed an earlier age at onset and a lower recurrence rate than heterozygotes and homozygotes for the long variant. Unipolar patients showed a trend toward the same difference. Data support a role for 5-HTTLPR in course of affective illness. PMID- 11788244 TI - Concomitant clozapine reduces smoking in patients treated with risperidone. AB - This pilot study examines the smoking behaviors of patients treated with either risperidone alone or in combination with clozapine. Smoking behavior was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results indicate that patients co-prescribed clozapine with risperidone smoke significantly less than patients treated with risperidone alone (19.1+/-9.3 vs. 37.8+/-19.1 ppm CO, respectively, P=0.03). These data are consistent with previous studies showing that clozapine treatment is associated with significantly reduced smoking behavior relative to other antipsychotic agents. PMID- 11788245 TI - ECNP Consensus Meeting March 2000. Guidelines for investigating efficacy in GAD. PMID- 11788246 TI - General thoracic surgery as a monospeciality--a realistic vision? PMID- 11788247 TI - Endovascular stent-grafting for descending thoracic aortic aneurysms. AB - OBJECTIVE: Endoluminal placement of covered stent-grafts emerges as a less invasive alternative to open surgical repair of thoracic aortic aneurysms (TAA). The present report describes our experience with endovascular stent-grafting in the treatment of descending TAA. METHODS: From 1997 to 2001, 28 descending TAA's were treated in 27 patients (17 male, mean age 70 years) by endovascular stent grafting. The aneurysms (mean diameter, 6.6 cm) had diverse causes, but the majority were due to atherosclerosis (71%). They were predominantly localized in the proximal (32%), central (39%), and distal part (22%) of the descending thoracic aorta. In two patients (7%), the entire thoracic aorta was treated. Preliminary subclavian-carotid artery transposition was performed in five patients. AneurX (n=6), Talent (n=9), and Excluder (n=13) stent-grafts were used. In 13 cases (46%), multiple stents were necessary for complete aneurysm exclusion. RESULTS: In 27 of 28 cases (96%), the endovascular stent-grafts were successfully deployed. In one patient, stent dislocation into the aneurysm required open surgical repair in a subsequent procedure. There was no operative mortality. None of the patients developed paraplegia or paraparesis. No distal embolization occurred. After a median follow-up of 21 months (range, 1-49 months), there was one non-related late death. There was no aneurysm rupture. Maximal aneurysm diameter either remained stable or decreased slightly over time in all but one patient with evidence of an endoleak. Endoleaks occurred in eight patients (29%) during follow-up. In five of them the endoleaks sealed spontaneously, whereas in two patients a distal extension was inserted. CONCLUSIONS: Endovascular repair of descending TAA's is a promising less-invasive alternative to open repair. Extended follow-up is necessary to determine its definite efficacy in the longer term. PMID- 11788248 TI - Quality of life after interventions on the thoracic aorta with deep hypothermic circulatory arrest. AB - OBJECTIVE: Assessment of quality of life (QL) in patients undergoing major surgical procedures is of increasing interest. We focused on surgery of the thoracic aorta requiring deep hypothermic circulatory arrest (DHCA). Aim of this study was to assess QL after thoracic aortic surgery with DHCA, using the Short Form 36 Health Survey (SF-36) questionnaire. METHODS: Between 01/94 and 12/99 212 (59.1%) out of a total of 359 interventions on the thoracic aorta were performed under DHCA, with an early mortality of 13.7% (28 patients). During an average follow-up of 3.2+/-1.3 years, 27 patients died (15.2%) and five patients (2.8%) were lost. A total of 145 patients (81.9%) had a complete follow-up. RESULTS: 125 of the 145 SF-36 questionnaire handed out were answered correctly (86.2%). In relation to a standard population (z=0), the most important deficits were found in physical function (z=-0.53) and role limitations because of physical health (z=-0.42). Good results were found regarding the aspect of pain (z=0.28), social functioning (z=0.02) and vitality (z=-0.02). Overall QL in patients having been operated for aortic aneurysm was better than for patients with acute type A dissection. CONCLUSION: Despite restrictions in physical functioning and role limitation because of physical health, QL in patients after interventions on the thoracic aorta with DHCA is fairly good and, for patients being operated for aortic aneurysm, comparable to an age-matched standard population. Patients having being operated electively for aortic aneurysm enjoyed a better QL than patients having been operated emergently for acute type A dissection. PMID- 11788249 TI - Early and long-term outcome in patients undergoing aortic root replacement with composite graft according to the Bentall's technique. AB - OBJECTIVE: The aims of this study were: (i) to evaluate the early and long-term outcome in patients undergoing aortic root replacement (ARR) with a composite graft; (ii) to identify the predictors for poor overall survival in this pool of patients. MATERIAL AND METHODS: Between January 1989 and December 2000, 212 patients underwent ARR with a CG. Mean age was 56+/-14 years, ranging from 16 to 77. Annuloaortic ectasia was the most frequent cause of aortic disease in this series, 81 (38%) patients, followed by atherosclerotic aneurysm 57 (27%) and type A acute aortic dissection 52 (24.5%). Marfan's syndrome was present in 37 (17.5%) patients. Duration of follow-up ranged from 1 to 120 months, mean 59+/-35 months. RESULTS: The overall hospital mortality was 16 (7.5%) patients. Eight of them had aortic dissection and four Marfan syndrome. The most frequently found complication resulted to be renal failure in 22 (10%) patients and low cardiac output in 15 (7%) patients. The incidence of perioperative myocardial infarction, neurological complications, respiratory complications, renal failure and coagulopathy incidence were significantly higher in patients with cardiopulmonary bypass (CPB) time >170 min, CA >40 min, and total aortic arch replacement. The actuarial survival at 1, 3 and 5 years resulted to be 91.8, 86 and 81.5%, instead the actuarial survival without re-operation resulted to be 89, 82 and 78%. The actuarial survival in patients with aortic dissection was significantly lower versus non-dissection (P=0.022). The multivariate analysis revealed the aortic dissection (P=0.03), age >65 years (P=0.014), associated coronary artery disease (P=0.002), NYHA functional class>/=3 (P=0.027), LVEF <35% (P=0.002) and total arch reconstruction (P=0.003) as strong predictors for poor overall survival in patients undergoing ARR. CONCLUSIONS: The ARR with a CG offers acceptable early and long-term outcome. The predictors for poor overall survival in patients undergoing ARR seems to be preoperative aortic dissection extended into the aortic arch, older age, depressed left ventricular function and associated coronary artery disease. PMID- 11788251 TI - Extensive use of polytetrafluoroethylene artificial grafts for prolapse of bilateral mitral leaflets. AB - OBJECTIVES: There are an increasing number of reports concerning mitral valve repair by reconstruction of the chordae tendinae with the use of expanded polytetrafluoroethylene (PTFE) sutures. However, little information is available about the extended application or results of this technique for extended prolapse of bilateral mitral leaflets, which is considered to be difficult to repair. METHODS: Between October 1993 and May 1998, 17 patients (age range 16-74 years) who had from moderate to severe mitral regurgitation as the result of a prolapse of bilateral leaflets underwent mitral valve repair by reconstruction of artificial chordae with CV-4 expanded PTFE sutures. Either bilateral or unilateral Kay's suture annuloplasty was also performed to correct annular dilatation in all patients. RESULTS: No operative death or late mortality was observed. Before discharge, immediate postoperative echocardiography showed less than moderate mitral regurgitation in 16 of 17 patients. The follow-up was completed in all cases by a clinical examination and serial echocardiograms, and the median follow-up period was 52 months (range 27-82 months). There was one failure that required re-operation because of worsening mitral regurgitation (elongation of the anchored side of papillary muscle). When the re-operated patient was excluded from the following data, the degree of mitral regurgitation, estimated by echocardiography performed at recent follow-up, was none in four patients, trivial in eight patients, and mild in four patients. The systolic and diastolic dimensions of the left ventricle decreased significantly (P<0.01). CONCLUSIONS: Because replacement of artificial chordae was not complicated and seemed to preserve fine relationships among leaflet tissues, chordae, and papillary muscles, we therefore suggest that the extensive use of PTFE artificial chordae appears to be a promising procedure for the repair of all kinds of mitral lesions causing mitral regurgitation. PMID- 11788250 TI - Clinical relevance of intracranial high intensity transient signals in patients following prosthetic aortic valve replacement. AB - OBJECTIVES: There has been frequent report on transcranially detected microembolic signals (HITS) following cardiac surgery using extracorporeal bypass support. The clinical relevance of HITS, however, has yet to be clarified. The incidence of thromboembolic events is increased following mechanical heart valve replacement. The purpose of this study was to quantify postoperative HITS after implantation of two types of prosthetic aortic valves and to compare both types of mechanical valves with respect to the generation of HITS. In addition, HITS rates were correlated with clinical, echocardiographical and laboratory findings. METHODS: Forty-two patients following implantation of either a Sorin Biomedica heart valve (n=22, group A) or a Tekna Duromedics mechanical valve (n=20, group B) were examined. A group of ten healthy volunteers served as control. Clinical, echocardiographic, carotid artery duplex and laboratory examinations were performed in all patients. A 60 min bilateral transcranial doppler monitoring of the medial cerebral artery (MCA) was also carried out in order to evaluate cerebral blood flow. RESULTS: In group A 14 of 22 patients were positive for HITS (53%), with an average of 16.4+/-19 HITS/pt.h. In group B 15 of 20 patients were HITS positive (75%) with an average amount of 14.4+/-24 HITS/pt.h. The incidence of HITS was not significantly different between the two groups. No correlation was seen between the HITS-rate/h and neurological findings, duplex sonographic results, mechanical valve size and anticoagulation regimen (P>0.05). However, a negative correlation was observed between patient age and HITS-rate (P=0.02) as well as between the NYHA degree and HITS-rate (P=0.018). The HITS-rate also correlated with postoperative time (P=0.042). No HITS were detected in the control group. CONCLUSIONS: HITS do not correlate with the individual clinical status and, thus, cannot predict the occurrence of neurological deficits in patients following mechanical aortic valve implantation. PMID- 11788252 TI - Myocardial perfusion correlates with improvement of systolic function of the left ventricle after CABG. Dobutamine echocardiography and Tc-99m-MIBI SPECT study. AB - OBJECTIVE: The aim of the study was to assess the effect of surgical revascularization [coronary artery bypass grafting (CABG)] on systolic function and perfusion of the left ventricle using dobutamine echocardiography (DE) and Tc 99m-MIBI SPECT (SPECT). METHODS: There were 32 patients mean age 52.2+/-7.2 years in whom DE and SPECT were performed before and 3-4 months after CABG using standard protocols. Wall motion score index (WMSI) and perfusion index (PI) were calculated. RESULTS: Significant improvement of WMSI at rest (1.44+/-0.46 vs 1.33+/-0.41; P=0.03) as well as after maximal dose of dobutamine (1.49+/-0.42 vs 1.39+/-0.44; P=0.02) was observed after CABG as compared to preoperative examination. Similar relation was observed during SPECT study. Perfusion index diminished significantly after revascularization during rest acquisition (2.19+/ 0.71 vs 1.93+/-0.70; P=0.0008) and after Dipirydamole administration (2.73+/-0.73 vs 2.20+/-0.69; P=0.0001) as compared to preoperative examination. We found correlation between PI and WMSI at rest before CABG (R=0.46; P=0.01), PI after Dipirydamole and WMSI after maximal dose of Dobutamine before CABG (R=0.37; P=0.04), PI and WMSI at rest after CABG (R=0.39; P=0.03), PI after Dipirydamole and WMSI after dobutamine after CABG (R=0.38; P=0.03). CONCLUSIONS: Surgical revascularization significantly improves both perfusion and contractility. Increased perfusion after CABG correlates with improvement of systolic function of the left ventricle. PMID- 11788253 TI - Off-pump coronary artery bypass surgery in the left ventricular dysfunction. AB - OBJECTIVE: The purpose of this study is to report our experience in off-pump coronary artery surgery in patients who have left ventricular dysfunction. METHODS: Off-pump coronary artery surgery was performed to 48 patients who were chosen randomly among 265 patients having two or more coronary artery disease and whose ejection fraction (EF) was less than 30%. In these patients fractioned shortening (FS) was evaluated by echocardiography, EF with multiple gated acquisition (MUGA) and ischaemic regions with myocardial perfusion scintigraphy both pre- and postoperatively. Coronary artery angiography was done to all patients at the end of the 1st year and patients were evaluated according to New York Heart Association (NYHA) classification. RESULTS: There were three deaths. The clinical situations of 41 of 45 patients (91.1%) improved after the operation. These four patients who didn't improve in NYHA status were the ones in whom complete revascularization couldn't be done. The FS and EF values were significantly increased at the 1st month, and 1st year. The constant perfusion defects and irreversible damaged areas changed into dynamic myocardial tissue in the 1st year scintigraphies. DISCUSSION: Off-pump CABG can be done with an acceptable mortality and clinic results in patients who have ventricular dysfunction. PMID- 11788254 TI - Preoperative risk prediction and intraoperative events in cardiac surgery. AB - OBJECTIVE: To examine the relationship between preoperative risk prediction and intraoperative events. METHODS: A total of 3118 patients operated in 1999 and 2000 at our institution were analysed, all of whom had their EuroSCORE collected prospectively. The intraoperative variables studied were consultant or trainee operating, long bypass time, long ischaemic time, return on bypass in theatre and use of intra-aortic balloon pump at the end of the procedure. The outcomes are reported as hospital mortality, prolonged length of stay in the intensive therapy unit (pLOS-ITU, >48 h) and death or pLOS-ITU. Risk models were constructed by logistic regression for predicting these three outcomes. RESULTS: With the exception of prolonged cross-clamp time, all variables analysed were independently predictive of a negative outcome. Trainee operating had an apparent protective effect. All risk models performed well. The area under the receiver operating characteristic (ROC) curve (95% CI) increased from 0.857 (0.81, 0.90) for EuroSCORE to 0.874 (0.83, 0.92) for the risk of death model. Similarly, the area under the ROC curve for the pLOS-ITU model increased from 0.687 (0.642, 0.732) to 0.734 (0.691, 0.777) and for the death or pLOS-ITU model from 0.717 (0.677, 0.756) to 0.757 (0.719, 0.795). CONCLUSIONS: Knowledge of adverse intraoperative events enhances preoperative risk prediction. This type of analysis could be used for identifying "near miss" outcomes in adult cardiac surgery. PMID- 11788255 TI - Congenital Heart Surgery Nomenclature and Database Project: update and proposed data harvest. AB - In 1998, the first report of the Society of Thoracic Surgery (STS) National Congenital Heart Surgery Database reported the clinical features of 18 congenital heart categories. The report provided a significant amount of important information and also highlighted the strengths and weaknesses of the existing database. Following this report, the STS Congenital Heart Surgery Committee, in cooperation with the European Association of Cardio-Thoracic Surgery and the European Congenital Heart Surgeons Foundation, initiated the International Congenital Heart Surgery and Nomenclature Database Project. The goal was to begin the standardization of nomenclature and reporting strategies and establish the foundations for an international congenital heart surgery database. The first report of the International Congenital Heart Surgery Nomenclature Project was published in the Annals of Thoracic Surgery in April 2000. The current report outlines modifications to the minimal dataset, as well as the diagnosis and procedure short lists. PMID- 11788256 TI - Surgical repair of congenital supravalvular aortic stenosis in children. AB - OBJECTIVE: Supravalvular aortic stenosis (SVAS) is an uncommon congenital cardiac anomaly characterized by varying degrees of left ventricular outflow tract obstruction beginning distal to the aortic valve. METHODS: Between March 1962 and December 2000, 101 consecutive patients underwent surgical correction for congenital SVAS at Riley Children's Hospital. There were 61 male (60%) and 40 female (40%) ranging in age from 3 month to 17 years (medium age, 6.1 years). Fourteen patients (14%) had Williams syndrome. Preoperatively, 11 patients were in New York Heart Association (NYHA) functional class I, 55 in class II, 28 in class III, and seven in class IV. Of the 101 patients, 73 (72%) had localized type SVAS and 28 (28%) diffuse type SVAS. RESULTS: Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apical aortic conduit or extensive endarterectomy with patch aortoplasty. The overall mean pressure gradient was reduced to 21 mmHg (P<0.001) in the early postoperative period. There were one early death (<30 days postoperatively) (1%), two (2%) late deaths, and 14 patients (14%) underwent one or two additional operation (n=17) in a follow-up period ranging from 6 months to 30 years (medium 9.4 years). Postoperatively, there were 72 patients (73%) in NYHA functional class I and 26 (27%) in class II. Overall survival including operative mortality was 98% at 10 years, 97% at 20 and at 30 years. CONCLUSION: Good surgical outcome of congenital SVAS can be achieved with the appropriate method of treatment in patients with both localized and diffuse SVAS. PMID- 11788257 TI - Chest trauma in children. AB - OBJECTIVES: Chest trauma in childhood is uncommon in clinical practice. The management and treatment principles of children with thoracic trauma were discussed with the data reported in the literature. METHODS: Of the chest injury diagnosed in 1653 patients, 225 were children in the last 17-year period. There were 199 boys (88.44%) and 26 girls (11.55%). The most common causes were blunt injuries in 135 cases (60%), stab wounds in 67 cases (29.77%) and gunshot wounds in 22 cases (9.77%). RESULTS: Out of 225, 217 patients were treated conservatively and eight patients were treated surgically. There was no mortality and morbidity. CONCLUSIONS: The prevalence of chest trauma in children due to blunt injuries is high in Turkey. Extremity injury is thought to be the most commonly associated extra-thoracic injury. However, thoracic trauma in children can be managed conservatively in most of the cases. PMID- 11788258 TI - Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients. AB - OBJECTIVE: Bronchoalveolar lavage (BAL) fluid provides a crucial tool for investigation of the cellular component of the deep lung spaces and hence to approach the alloreactive response following lung transplantation. This study investigated whether BAL cell profiles can assist for the diagnosis of certain postoperative complications. METHODS: We conducted a retrospective analysis of both transbronchial biopsy and bronchoalveolar lavage materials in a series of 26 consecutive lung transplant recipients (LTR) in relationship with their clinical status at the time of the procedure. BAL fluid was subjected to cell morphology as well as flow cytometric phenotypic analyses. The samples were labeled as follows: normal transplant in clinically stable and healthy recipients, n=58; acute rejection (AR), n=58; infection (INF), n=31; and obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS) n=27. RESULTS: Total BAL cell counts were the highest in INF. Lymphocytic alveolitis was suggestive of both acute allograft rejection and CMV viral infection, with a combined significant increased HLA-DR positive cells in AR. Alveolar neutrophilia with an increased CD4/CD8 ratio was correlated with the diagnosis of OB. The neutrophil percentages, HLA-DR and CD57 positive cells were significantly higher when an infection was present. CONCLUSION: These findings suggest that BAL cell analysis could give complementary information of histological data and further insight into immunologic events after lung allograft. A longitudinal surveillance of BAL cell profiles in an individual patient may be suggestive for a preclinical state of posttransplant acute rejection, bacterial infection and obliterative bronchiolitis. PMID- 11788259 TI - Minimally invasive video-endoscopic sympathectomy by use of a transaxillary single port approach. AB - OBJECTIVES: This is a prospective study to evaluate the long-term outcome and the value of a transaxillary single port thoracic sympathectomy by use of a modified paediatric cystoresectoscope in a consecutive series of patients with facial blushing and/or hyperhidrosis. MATERIALS AND METHODS: All patients who underwent a thoracic transsection of the sympathetic chain from T2 to T5 by use of a 7-mm single port approach and a modified urologic electroresectoscope between 1996 and 1998 were prospectively analysed regarding postoperative morbidity and outcome (clinical evaluation, visual analogue scale) in order to validate this technique. RESULTS: 37 patients (18 men, 19 women) with an age ranging from 18 to 67 years (mean 34 years) underwent 74 bilateral video-assisted thoracic sympathectomies. The indications for sympathectomy included facial blushing in 32%, hyperhidrosis in 52%, or both in 16% of the patients. Ninety-five percent of the patients were discharged from the hospital on the next day, the 30-day mortality was zero, and there was no conversion to an open procedure. A severe complication with crossed emboli and motor aphasia was noted. A unilateral transient Horner's syndrome was observed in two patients. Three-month follow-up revealed an excellent cosmetic and functional result, with no residual pain. Complete relief of symptoms was observed in 89% and in 100% of the patients with facial blushing and palmar hyperhidrosis, respectively, after a follow-up of 34.5 months. Recurrence of the symptoms after initial regression was noted in 5.7% of the patients 3 years after surgery. Compensatory sweating of the lower extremities was significantly increased in patients with hyperhidrosis and facial blushing; however, sweating of the trunk was only increased in patients with hyperhidrosis. Improvement of quality of life was observed in 94.6% of the patients. CONCLUSIONS: Single port thoracoscopic sympathectomy by use of a modified paediatric cystoresectoscope and transsection from T2 to T5 gives an excellent cosmetic and functional outcome, with better results in patients with hyperhidrosis. PMID- 11788260 TI - Cervical mediastinoscopy after total laryngectomy and radiotherapy: its feasibility. AB - OBJECTIVE: The feasibility of cervical mediastinoscopy after total laryngectomy and radiotherapy has not been documented. METHODS: We describe our experience with cervical mediastinoscopy in two patients with total laryngectomy and radiotherapy for squamous cell carcinoma and had a Blom-Singer speaking tracheostomy valve in situ. Both patients presented with mediastinal lymphadenopathy and radiographic features suggesting a new pulmonary malignancy. RESULTS: Rigid bronchoscopy and cervical mediastinoscopy were undertaken and paratracheal and subcarinal lymph nodes were biopsied. Both patients made uneventful post operative recovery. Mediastinal lymph node biopsy was definitive in deciding their further care. CONCLUSION: Cervical mediastinoscopy is feasible in patients with total laryngectomy, tracheostomy and radiotherapy. PMID- 11788263 TI - A right bronchial rupture. PMID- 11788262 TI - Late complications of coloesophagoplasty and long-term features of adaptation. AB - OBJECTIVES: Revisional surgery of late complications after 141 substernal by-pass operations (1962-1990), except three cases with isoperistaltic (except seven with anisoperistaltic) transverse colon grafts for caustic esophageal strictures, are presented. Long-term adaptation of the grafts was investigated with cineradiographical and histochemical methods. METHODS: Correction of the "pseudodiverticulum" of the proximal anastomosis as a complication of the standard by-pass procedure (in five patients) was achieved by closure of the esophagus below the anastomosis or by end-to-end reanastomosis. Cervical anastomosis stricture (in seven) was solved either by plasty or resection and a similar reanastomosis. Delayed passage due to an intra-abdominal redundant graft (in five) was managed by abdominal shortening coloplication or by side-to-side gastrocolostomy. Late pyloric obstruction as a cause of gastrocolic reflux required pyloroplasty in two instances. Mixed barium-bread bolus for a cineradiographical transit study and periodic acid Schiff reaction plus Alcian Blue staining for a mucopolysaccharide search were used 8 years after the operations. RESULTS: In all but one case, redo surgery was successful. Characteristic coordinated multihaustral propulsive movement developed in the distal colonic segment, playing a secondary but active role in the final phase of swallowing in isoperistaltic substitution. These grafts were free from gastrocolic reflux. Augmentation of neutral mucopolysaccharide was observed on the surface and in the Lieberkuhn glands of colonic mucosa. CONCLUSIONS: This experience attests that the majority of late complications following colonic esophageal substitution may be corrected by revisional surgery. The predominantly automatic propulsive movements of the isoperistaltically interposed grafts seem to provide an effective antireflux barrier against the gastrocolic reflux if some technical requirements (high gastric anastomosis, good gastric drainage, etc.) are respected. The graft mucosa showed signs of a positive adaptation. The best functional results were achieved by isoperistaltically interposed left colic transplants, which may be considered as an ideal graft (both technically and functionally) in extensive caustic strictures. PMID- 11788261 TI - Mediastinal reinforcement after induction therapy and pneumonectomy: comparison of intercostal muscle versus diaphragm flaps. AB - OBJECTIVE: Prospective non-randomised comparison of full-thickness pedicled diaphragm flap with intercostal muscle flap in terms of morbidity and efficiency for bronchial stump coverage after induction therapy followed by pneumonectomy for non-small cell lung cancer (NSCLC). METHODS: Between 1996 and 1998, a consecutive series of 26 patients underwent pneumonectomy following induction therapy. Half of the patients underwent mediastinal reinforcement by use of a pedicled intercostal muscle flap (IF) and half of the patients by use of a pedicled full-thickness diaphragm muscle flap (DF). Patients in both groups were matched according to age, gender, side of pneumonectomy and stage of NSCLC. Postoperative morbidity and mortality were recorded. Six months follow-up including physical examination and pulmonary function testing was performed to examine the incidence of bronchial stump fistulae, gastro-esophageal disorders or chest wall complaints. RESULTS: There was no 30-day mortality in both groups. Complications were observed in one of 13 patients after IF and five of 13 after DF including pneumonia in two (one IF and one DF), visceral herniations in three (DF) and bronchopleural fistula in one patient (DF). There were no symptoms of gastro-esophageal reflux disease (GERD). Postoperative pulmonary function testing revealed no significant differences between the two groups. CONCLUSIONS: Pedicled intercostal and diaphragmatic muscle flaps are both valuable and effective tools for prophylactic mediastinal reinforcement following induction therapy and pneumonectomy. In our series of patients, IF seemed to be associated with a smaller operation-related morbidity than DF, although the difference was not significant. Pedicled full-thickness diaphragmatic flaps may be indicated after induction therapy and extended pneumonectomy with pericardial resection in order to cover the stump and close the pericardial defect since they do not adversely influence pulmonary function. PMID- 11788265 TI - Coronary arteriovenous fistulas from both coronary arteries to pulmonary artery. PMID- 11788264 TI - Right coronary and aortic dissection. PMID- 11788266 TI - Echinococcus cyst of the left ventricle in 10-year-old patient. PMID- 11788267 TI - Windsock deformity of the mitral valve--a late presentation of endocarditis. PMID- 11788268 TI - Aortic arch replacement using a four-branched aortic arch graft. AB - Surgical repair for aortic arch aneurysms is associated with considerable mortality and morbidity. Adequate brain protection is essential. Experience of aortic arch repair in six patients using a four-branched arch graft is described. There were two emergency and three reoperations. One patient had ruptured aneurysm. Hypothermic cardiopulmonary bypass (18-22 degrees C) was employed. A four-branched polymer albumin-coated arch graft was used. The fourth branch of the graft was used for secondary arterial cannulation to ensure continuous brain circulation. One hospital death occurred. No permanent neurological event occurred. The four-branched arch graft facilitates fashioning arch branch anastomoses and provides better brain protection. PMID- 11788269 TI - The use of pedicled pleural flaps for the repair of pericardial defects, resulting after intrapericardial pneumonectomy. AB - We report our technique for the repair of large pericardial defects resulting after intrapericardial pneumonectomy for locally advanced non-small cell lung carcinoma, using pedicled pleural flaps. Creation of a pedicled pleural flap, large enough to cover the pericardial defect, performing blunt dissection of parietal pleura from the inferior edge of the thoracotomy incision and suturing it in the defect margins, is an easy, safe and effective technique for the prevention of cardiac herniation. Pedicled pleural flaps are an excellent material, not very popular nowadays, for the repair of pericardial defects resulting after intrapericardial pneumonectomy, when it is possible to create a pleural flap. PMID- 11788270 TI - Video-assisted limited anterior thoracotomy approach for lingular segmentectomy and left anterior descending coronary artery bypass. AB - Minimally invasive cardiothoracic combined surgery was performed successfully in an octogenerian with left anterior descending coronary artery disease and concurrent adenocarcinoma in the lingular segment of emphysematous lung. Through a limited anterior 4th intercostal thoracotomy, left anterior descending coronary artery bypass grafting without cardiopulmonary bypass was carried out using the left internal thoracic artery (LITA) and the interposed vein graft, and subsequently lingular segmentectomy was accomplished. Videothoracoscopy via a single port placed at the 5th intercostal space below the left nipple was useful for LITA mobilization, lymph nodes sampling and endo-cutter guidance. PMID- 11788271 TI - Ascending aortic replacement through right thoracotomy. AB - A 62-year-old woman with a history of esophageal resection and colon interposition with anterosternal subcutaneous tunnel required replacement of the ascending aorta due to dissecting aortic aneurysm. Preoperative three-dimensional computed tomography enabled us to reveal that right thoracotomy could offer an ascending aortic operation. The patient underwent successful operation under hypothermic circulatory arrest and the right anterolateral thoracotomy provided safe exposure of the diseased ascending aorta even when the suprasternal tunnel precluded conventional median sternotomy. PMID- 11788272 TI - Intraoperative acute type A dissection caused by an intra-aortic filter (EMBOL-X) in a patient undergoing mitral valve re-replacement for acute endocarditis. AB - We report on the case of a 60-year-old male patient who underwent mitral valve re replacement for acute mechanical valve endocarditis. When an intra-aortic filter (EMBOL-X Inc, Mountain View, CA) was inserted through the arterial cannula in order to prevent embolization from a floating thrombus attached to the mitral valve prosthesis, our patient developed acute type A aortic dissection. This, to our knowledge, is the first report on this kind of complication using intra aortic filter systems. Here we discuss a potential mechanism that might have led to the event of acute type A dissection in our case. Furthermore we point out strategies that might help to prevent this life-threatening complication in the future. PMID- 11788273 TI - Management of anomalous right coronary arteries encountered during aortic valve surgery. AB - We experienced three cases with anomalous right coronary arteries during aortic valve surgery. By rotating a Freestyle bioprosthesis by a subcoronary technique, the anomalous artery was secured in one patient. The anomalous artery was injured during the routine aortotomy incision in another patient; a saphenous vein graft was interposed between the ascending aorta and the separated artery. In the third patient, a subannular prosthetic valve was chosen to avoid obstructing the anomalous orifice. PMID- 11788274 TI - Anomalous origin of the left coronary artery from the pulmonary artery A case using the autologous pulmonary arterial wall graft. AB - A 10-year-old girl with anomalous origin of the left coronary artery from the pulmonary artery underwent a two coronary system reconstruction with a new technique. Her left coronary artery was stenotic next to its origin and had a severe adhesion with the aorta. We made a bypass grafting between the aorta and the left coronary artery with a roll shaped transected main pulmonary arterial wall graft. The postoperative angiogram showed a good patency of a reconstructed left coronary artery. This technique is considered useful surgical option for bypass grafting to the left coronary artery when the left coronary artery has an obstructive lesion or a difficulty to dissect and mobilize. PMID- 11788275 TI - Reoperative revascularization of an occluded left subclavian artery and left internal mammary artery ostial stenosis. AB - An ostial stenosis of the left internal mammary artery graft anastomosed to the left anterior descending artery was responsible for unstable angina in a patient with a previous coronary artery bypass graft. A T-shape arterectomy was performed between the left subclavian artery and left internal mammary artery. Successful revascularization of the lesion was achieved with a carotid-to-subclavian bypass and surgical ostial plasty extending to the proximal left internal mammary graft using a Hemashild a graft. This procedure was performed through a transverse supraclavicular incision to avoid potential hazards of a redo median sternotomy. PMID- 11788276 TI - Coronary revascularization after arterial switch operation. AB - We report two cases presenting bilateral coronary artery obstruction after arterial switch operation. The first patient underwent bilateral internal thoracic artery grafting to the left and right coronary arteries. The other patient, presenting a single coronary ostium, underwent surgical coronary ostial angioplasty in concomitance to proximal arterioplasty of both coronary arteries employing a single "pantaloon" shape autologous pericardial patch. Both patients survived and, at 1 year and 9 months after the coronary revascularization procedures, the coronary angiography demonstrated a good patency of the internal thoracic grafts and excellent ostial plasty results, respectively. A complete literature review of patients undergoing different coronary revascularization procedures after arterial switch operation is reported. PMID- 11788277 TI - Pseudoaneurysm of subclavian artery 21-years after staged repair of tetralogy of Fallot. AB - Three cases of pseudoaneurysm of subclavian artery in long-term follow-up after staged repair of tetralogy of Fallot are described. The angiographical study revealed that aneurysms were located in the systemic end area of previously ligated modified Blalock-Taussing shunt. Aneurysmectomy with resection of a shunt and segment of subclavian artery was performed. We believe division of a prosthetic shunt should be routinely performed during complete repair of tetralogy to prevent morbidity in the long-term follow-up period. PMID- 11788278 TI - Retropharyngeal hematoma--a rare complication of anticoagulant therapy. AB - Anticoagulation is routinely employed in cardiac surgery following mechanical valve replacement. Warfarin is the most common agent used for anticoagulation. Bleeding, internal or external, remains the major complication with anticoagulant therapy. The risk is known to be higher with INR levels above 4.5. We report a case of a retropharyngeal hematoma following trivial blunt trauma to a patient whose INR had shot up to 6.8 and also discuss its management. PMID- 11788279 TI - Epicardial haematoma: rare cause of acute myocardial ischaemia. AB - Pericardial effusion and coronary dissection are well known complications of percutaneous transluminal coronary angioplasty (PTCA). We report a rare case of sub-epicardial haematoma after PTCA, leading to local compression and cardiogenic shock. We discuss the successful management of this problem. PMID- 11788280 TI - Delayed heart perforation after blunt trauma. AB - A 33-year-old patient was hospitalized after a blunt chest trauma with a left flail chest. Six hours after admission to the intensive care unit the patient suddenly developed hypotension and tachycardia. His left chest tube drained 1.5 l of blood within minutes. Immediate resuscitation and emergency sternotomy with left anterolateral extension was performed for pericardial tamponade secondary to left ventricular perforation due to a sharp rib fragment. Outcome was favourable and the patient was operated on for his flail chest by internal stabilization the next day. PMID- 11788281 TI - Primary malignant mesenchymoma of the heart. AB - Primary malignant cardiac tumours are uncommon, and cardiac malignant mesenchymoma is extremely rare. A case of primary malignant mesenchymoma in a 41 year-old woman arousing from the left atrial septum, obstructing the mitral orifice by passing through it into the left ventricle is described. The tumour was fully resected, and adjuvant chemotherapy was applied, but the patient had died by tumour recurrence in 8 months. PMID- 11788282 TI - A leiomyosarcoma of the oesophagus presenting incidentally without dysphagia. AB - Leiomyosarcoma is a rare tumour that accounts for 0.5% oesophageal sarcomas. The most common presenting symptom is dysphagia. This report presents a case of oesophageal leiomyosarcoma in a 56-year-old Caucasian man found incidentally while being investigated for refractory cough. There was no history of dysphagia in spite of tumour mass occupying most of the oesophageal lumen. The leiomyosarcoma was managed successfully with surgical resection and adjuvant radiotherapy. The patient remains disease free after 15 months after surgical intervention. The unusual case presentation is discussed and the surgical management of this rare condition reviewed. PMID- 11788284 TI - Giant dumbbell-shaped gastroenteric cyst presenting with total situs inversus. AB - We present a case of an 8-month-old boy with total situs inversus, who had a giant dumbbell-shaped gastroenteric cyst. The concurrence of these entities has never been reported previously. The cyst occupied a large space in the mediastinum and involved both hemithoraces. PMID- 11788283 TI - Coexisting achalasia and paraoesophageal hiatal hernia. AB - Disorders of the oesophagus present a diagnostic and therapeutic challenge. The presenting symptoms of dysphagia, reflux, pain and vomiting are almost universal, irrespective of the underlying pathology. A combination of endoscopy, barium studies, pH studies and manometry are often required to determine the exact diagnosis and to plan the most effective treatment. Paraoesophageal hiatal hernia is an uncommon condition, present in 14% of all hiatal hernias, which requires urgent correction to prevent life-threatening complications. It is unusual for other oesophageal disorders to coexist. We present a case where achalasia and a paraoesophageal hiatal hernia probably coexisted. PMID- 11788285 TI - Cololaryngostomy procedure in caustic esophageal burns. AB - The study presented herein was undertaken to report an original case of cololaryngostomy operation in caustic esophageal burns. Cololaryngostomy application to a chronic caustic esophageal burn case is reported with a detailed literature review of the topic. For the first time in the world, the larynx was used for the integrity of the gastrointestinal system by applying a cololaryngostomy procedure as it was found to be the only intact and reliable tissue in the operation. The patient started to gain weight in a 3-month period. Oral nutrition and speech were also achieved. Caustic injury to the upper aerodigestive system with scarring of the pharynx, hypopharynx and esophagus is an important reconstructive problem. In reconstruction, the aim should be the supplementation of both oral nutrition and speech. PMID- 11788286 TI - Modified slide tracheoplasty for the management of tracheobroncopathia osteochondroplastica. AB - In this paper we report a case with tracheobroncopathia osteochondroplastica presented with a long segmental tracheal stenosis. Modified slide tracheoplasty was undertaken for the management of the stenosis. In our modification, the oblique tracheal cut was performed from left to right to widen the latero-lateral dimension of tracheal lumen. We assume that preservation of the lateral longitudinal vessels of the trachea results in better healing at the suture line. Postoperative course was uneventful and the patient remains on clinical follow-up for 15 months without any problem.